Index Penyakit

ATP III Classification of LDL, Total, HDL Cholesterol and Triglycerides (mg/dL)

LDL Cholesterol
<100 Optimal
100-129 Near optimal/above optimal
130-159 Borderline high
160-189 High
>/=190 Very high
Total Cholesterol
<200 Desirable
200-239 Borderline high
>/=240 High
HDL Cholesterol
<40 Low
>/=60 High
Triglycerides
<150 Optimal
150-199 Borderline high
200-499 High
>500 Very high

DSM-IV Diagnostic Criteria for Bulimia Nervosa

A. Recurrent episodes of binge eating. An episode of binge eating is characterized by both of the following:

(1) Eating, in a discrete period of time (e.g., within any 2-hour period), an amount of food that is definitely
larger than most people would eat during a similar period of time and under similar circumstances.

(2) A sense of lack of control over eating during the episode (e.g., a feeling that one cannot stop eating or
control what or how much one is eating).

B. Recurrent inappropriate compensatory behavior in order to prevent weight gain, such as self-induced
vomiting, misuse of laxatives, diuretics, enemas, or other medications; fasting, or excessive exercise.

C. The binge eating and inappropriate compensatory behaviors occur, on average, at least twice a week for
three months.

D. Self-evaluation is unduly influenced by body shape and weight.

E. The disturbance does not occur exclusively during episodes of Anorexia Nervosa.

Type: Purging Type vs. Non-purging Type (exercise & fasting to compensate).

Diagnostic Criteria for Amiodarone-Induced Pulmonary Toxicity (APT)

The clinical diagnosis of amiodarone-induced pulmonary toxicity (APT) requires two or more of the
following criteria:

1
 1. new onset of pulmonary symptoms such as dyspnea, cough, or pleuritic chest pain;
2. new chest radiographic abnormality such as an interstitial or alveolar infiltrate;
3. a decrease in the DLCO of 20% from the pretreatment value, or if none is available, a value less
than 80% of predicted;
4. abnormal lung uptake with gallium-67 radioisotope; and
5. characteristic histologic changes of lung tissue obtained by bronchoscopic or open lung biopsy.

Exclusion of alternative etiologies such as congestive heart failure, infection, or malignancy.

DLCO= diffusion capacity of the lung for carbon monoxide

Braunwald Classification of Unstable Angina (UA)

Clinical Circumstances
A B C
Develops in presence of Develops in the Develops within 2
extracardiac condition absence of weeks after acute
Severity that intensifies extracardiac condition myocardial infarction
myocardial ischemia (primary UA) (postinfarction UA)
(secondary UA)
I New onset of severe angina IA IB IC
or accelerated angina; no
rest pain
II Angina at rest within past IIA IIB IIC
month but not within
preceding 48 hr (angina at
rest, subacute)
III Angina at rest within 48 hr IIIA IIIB Troponin IIIC
(angina at rest, acute) negative
IIIB Troponin positive

hr, hours; IAM, myocardial infarction; UA, unstable angina.

Common Diagnostic Criteria for Left and Right Atrial Abnormalities

Left Atrial Abnormality

Prolonged P wave duration of >120 msec in lead II
Prominent notching of the P wave, usually most obvious in lead II, with an interval between the
notches of >40 msec (p mitrale)
Ratio between the duration of the P wave in lead II and the duration of the PR segment of >1.6
Increased duration and depth of the terminal negative portion of the P wave in lead V1 (the P
terminal force) so that the area subtended by it exceeds 0.04 mm-sec (Morris index)
Leftward shift of the mean P wave axis to between -30 and +45 degrees

Right Atrial Abnormality

Peaked P waves with amplitudes over 250 muV in lead II (p pulmonale)
Rightward shift of the mean P wave axis to above 75 degrees
Increased area under the initial positive portion of the P wave in lead V1 to >0.06 mm-sec

Boston Criteria for Diagnosing Heart Failure

2
Criterion Point value
Category I: history
Rest dyspnea 4
Orthopnea 4
Paroxysmal nocturnal dyspnea 3
Dyspnea while walking on level area 2
Dyspnea while climbing 1
Category II: physical examination
Heart rate abnormality (1 point if 91 to 110 beats per minute; 2 1 or 2
points if more than 110 beats per minute)
Jugular venous elevation (2 points if greater than 6 cm H2O; 3 2 or 3
points if greater than 6 cm H2O plus hepatomegaly or edema)
Lung crackles (1 point if basilar; 2 points if more than basilar) 1 or 2
Wheezing 3
Third heart sound 3
Category III: chest radiography
Alveolar pulmonary edema 4
Interstitial pulmonary edema 3
Bilateral pleural effusion 3
Cardiothoracic ratio greater than 0.50 3
Upper zone flow redistribution 2

No more than 4 points are allowed from each of three categories; hence the composite score (the sum of the
subtotal from each category) has a possible maximum of 12 points. The diagnosis of heart failure is
classified as "definite" at a score of 8 to 12 points, "possible" at a score of 5 to 7 points, and "unlikely" at a
score of 4 points or less.

Diagnostic Criteria for Thromboangiitis Obliterans (Buergers Disease)

Since specificity of Buergers disease is characterized by peripheral ischemia of an inflammatory nature

and with a self-limiting course, diagnostic criteria should be discussed from clinical of view.

Several different criteria have been proposed for the diagnosis of thromboangiitis obliterans:

Diagnostic Criteria of Shionoya:

Smoking history;
Onset before the age of 50 years;
Infrapopliteal arterial occlusions;
Either arm involvement or phlebitis migrans;
Absence of atherosclerotic risk factors other than smoking.
Diagnostic Criteria of Olin
Age younger than 45 years
Current or recent history of tobacco use
Presence of distal extremity ischemia indicated by claudication, pain at rest, ischemic ulcers or
gangrenes, and documented by non-invasive vascular testing;
Exclusion of autoimmune diseases, hypercoagulable states and diabetes mellitus;
Exclusion of a proximal source of embolization by echocardiography and arteriography;
Consistent arteriographic findings in the clinically involved and noninvolved limbs

Criteria for Chronic Stable Refractory Angina

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The criteria for chronic stable refractory angina were defined by Mannheimer and colleagues in 2002 as "a
chronic condition characterized by the presence of angina caused by coronary insufficiency in the presence
of coronary artery disease which cannot be controlled by a combination of medical therapy, angioplasty and
coronary bypass surgery. The presence of reversible myocardial ischemia should be clinically established to
be the cause of the symptoms. Chronic is defined as a duration of more than 3 months.

Classification and Severity of Angina

Class I

No angina with ordinary physical activity (e.g., walking, climbing stairs). Angina with strenuous or
prolonged exertion.

Class II

Early-onset limitation of ordinary activity (e.g., walking rapidly or walking >2 blocks; climbing stairs
rapidly or climbing >1 flight); angina may be worse after meals, in cold temperatures, or with emotional
stress.

Class III

Marked limitation of ordinary activity.

Class IV

Inability to carry out any physical activity without chest discomfort. Angina occurs during rest.

Diagnostic Criteria for Diastolic Heart Failure

Diastolic heart failure is defined as a condition caused by increased resistance to the filling of one or both
ventricles; this leads to symptoms of congestion from the inappropriate upward shift of the diastolic
pressure-volume relation.

Definitive diastolic heart Probable diastolic heart failure* Possible diastolic heart failure
failure
Definitive evidence of Same as definitive Same as definitive
congestive heart failure
and and and
Objective evidence of normal Same as definitive Left ventricular ejection fraction of
left ventricular systolic function 50 percent or more not measured
in proximity of event within 72 hours of event
and and and
Objective evidence of left No conclusive information on left Same as probable
ventricular diastolic ventricular diastolic function
dysfunction
*- Patients who have definitive evidence of congestive heart failure and objective evidence of normal left
ventricular systolic function in proximity of event are accepted as having probable diastolic heart failure

4
provided that mitral valve disease, cor pulmonale, primary volume overload, and noncardiac causes are
excluded.
- Clinical symptoms and signs, supporting chest radiography, typical clinical response to diuretics with or
without elevated left ventricular filling pressure, or low cardiac index.
- Left ventricular ejection fraction of 50 percent or more within 72 hours of event.
- Abnormal left ventricular relaxation or filling or distensibility indices on catheterization.

Duke Criteria for Infective Endocarditis (IE)

Major criteria:
A. Positive blood culture for Infective Endocarditis
1- Typical microorganism consistent with IE from 2 separate blood cultures, as noted below:
viridans streptococci, Streptococcus bovis, or HACEK* group, or
community-acquired Staphylococcus aureus or enterococci, in the absence of a primary focus
or
2- Microorganisms consistent with IE from persistently positive blood cultures defined as:
2 positive cultures of blood samples drawn >12 hours apart, or
all of 3 or a majority of 4 separate cultures of blood (with first and last sample drawn 1 hour apart)
B. Evidence of endocardial involvement
1- Positive echocardiogram for IE defined as :
oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or
on implanted material in the absence of an alternative anatomic explanation, or
abscess, or
new partial dehiscence of prosthetic valve
or
2- New valvular regurgitation (worsening or changing of preexisting murmur not sufficient)

Minor criteria:

Predisposition: predisposing heart condition or intravenous drug use

Fever: temperature > 38.0 C (100.4 F)
Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm,
intracranial hemorrhage, conjunctival hemorrhages, and Janeway lesions
Immunologic phenomena: glomerulonephritis, Osler's nodes, Roth spots, and rheumatoid factor
Microbiological evidence: positive blood culture but does not meet a major criterion as noted
above or serological evidence of active infection with organism consistent with IE
Echocardiographic findings: consistent with IE but do not meet a major criterion as noted above

Clinical criteria for infective endocarditis requires:

Two major criteria, or
One major and three minor criteria, or
Five minor criteria

*HACEK group: Haemophilus sp, Actinobacilius actinomycetemcomitans, Cardiobacterium hominis,

Eikenella rodens y Kingella sp

Estimate of 10-Year Risk for Coronary Heart Disease for Men (Framingham Point Scores)

Coronary Heart Disease (CHD) score sheet for men using TC or LDL-C categories. Uses age, TC (or LDL-
C), HDL-C, blood pressure, diabetes, and smoking. Estimates risk for CHD over a period of 10 years based
on Framingham experience in men 30 to 74 years old at baseline. Average risk estimates are based on
typical Framingham subjects, and estimates of idealized risk are based on optimal blood pressure, TC 160
to 199 mg/dL (or LDL 100 to 129 mg/dL), HDL-C of 45 mg/dL in men, no diabetes, and no smoking. Use

5
of the LDL-C categories is appropriate when fasting LDL-C measurements are available. Pts indicates
points.

Step 1

Age
Years LDL Pts Chol Pts
30-34 -1 [-1]
35-39 0 [0]
40-44 1 [1]
45-49 2 [2]
50-54 3 [3]
55-59 4 [4]
60-64 5 [5]
65-69 6 [6]
70-74 7 [7]

Step 2

LDL-C
(mg/dl) (mmol/L) LDL Pts
<100 <2.59 -3
100-129 2.60-3.36 0
130-159 3.37-4.14 0
160-190 4.15-4.92 1
>/=190 >4.92 2

Cholesterol
(mg/dl) (mmol/L) Chol Pts
<160 <4.14 [-3]
160-199 4.15-5.17 [0]
200-239 5.18-6.21 [1]
240-279 6.22-7.24 [2]
>/=280 >/=7.25 [3]

Step 3

HDL-C
(mg/dl) (mmol/L) LDL Pts Chol Pts
<35 <0.90 2 [2]
35-44 0.91-1.16 1 [1]
45-49 1.17-1.29 0 [0]
50-59 1.30-1.55 0 [0]
>/=60 >/=1.56 -1 [-2]

Step 4

Blood Pressure
Systolic Diastolic (mmHg)
(mmHg) <80 80-84 85-89 90-99 >/=100

6
 <120 0 [0] pts
120-129 0 [0] pts
130-139 1 [1] pts
140-159 2 [2] pts
>/=160 3 [3] pts

Note: When systolic and diastolic pressures provide different estimates for point scores, use the higher
number

Step 5

Diabetes
LDL Pts Chol Pts
No 0 [0]
Yes 2 [2]

Step 6

Smoker
LDL Pts Chol Pts
No 0 [0]
Yes 2 [2]

Step 7 (sum from steps 1-6)

Adding up the points

Age
LDL-C or Chol
HDL-C
Blood Pressure
Diabetes
Smoker
Point total

Step 8 (determine CHD risk from point total)

CHD Risk
LDL Pts Total 10 Yr CHD Risk Chol Pts Total 10 Yr CHD Risk
<-3 1%
-2 2%
-1 2% [<-1] [2%]
0 3% [0] [3%]
1 4% [1] [3%]
2 4% [2] [4%]
3 6% [3] [5%]
4 7% [4] [7%]
5 9% [5] [8%]
6 11% [6] [10%]
7 14% [7] [13%]
8 18% [8] [16%]

7
 9 22% [9] [20%]
10 27% [10] [25%]
11 33% [11] [31%]
12 40% [12] [37%]
13 47% [13] [45%]
>/=14 >/=56% [>/=14] [>/=53%]

Step 9 (compare to average person your age)

Comparative Risk
Age (Years) Average 10 Yr Average 10 Yr Low** 10 Yr
CHD Risk Hard* CHD CHD Risk
Risk
30-34 3% 1% 2%
35-39 5% 4% 3%
40-44 7% 4% 4%
45-49 11% 8% 4%
50-54 14% 10% 6%
55-59 16% 13% 7%
60-64 21% 20% 9%
65-69 25% 22% 11%
70-74 30% 25% 14%

* Hard CHD events exclude angina pectoris

** Low risk was calculated for a person the same age, optimal blood pressure, LDL-C 100-129 mg/dl or
cholesterol 160-199 mg/dl, HDL-C 45 mg/dl, for men or 55 mg/dl for women, non-smoker, no diabetes.

Risk estimates were derived from the experience of the Framingham Heart Study, a predominantly
Caucasian population in Massachusetts, USA

Key
Color Relative Risk
Green Very low
White Low
Yellow Moderate
Rose High
Red Very high

Estimate of 10-Year Risk for Coronary Heart Disease for Women (Framingham Point Scores)

Coronary Heart Disease (CHD) score sheet for women using TC or LDL-C categories. Uses age, TC, HDL-
C, blood pressure, diabetes, and smoking. Estimates risk for CHD over a period of 10 years based on
Framingham experience in women 30 to 74 years old at baseline. Average risk estimates are based on
typical Framingham subjects, and estimates of idealized risk are based on optimal blood pressure, TC 160
to 199 mg/dL (or LDL 100 to 129 mg/dL), HDL-C of 55 mg/dL in women, no diabetes, and no smoking.
Use of the LDL-C categories is appropriate when fasting LDL-C measurements are available. Pts indicates
points.

8
Step 1

Age
Years LDL Pts Chol Pts
30-34 -9 [-9]
35-39 -4 [-4]
40-44 0 [0]
45-49 3 [3]
50-54 6 [6]
55-59 7 [7]
60-64 8 [8]
65-69 8 [8]
70-74 8 [8]

Step 2

LDL-C
(mg/dl) (mmol/L) LDL Pts
<100 <2.59 -2
100-129 2.60-3.36 0
130-159 3.37-4.14 0
160-190 4.15-4.92 2
>/=190 >4.92 2

Cholesterol
(mg/dl) (mmol/L) Chol Pts
<160 <4.14 [-2]
160-199 4.15-5.17 [0]
200-239 5.18-6.21 [1]
240-279 6.22-7.24 [1]
>/=280 >/=7.25 [3]

Step 3

HDL-C
(mg/dl) (mmol/L) LDL Pts Chol Pts
<35 <0.90 5 [5]
35-44 0.91-1.16 2 [2]
45-49 1.17-1.29 1 [1]
50-59 1.30-1.55 0 [0]
>/=60 >/=1.56 -2 [-3]

Step 4

Blood Pressure
Systolic Diastolic (mmHg)
(mmHg) <80 80-84 85-89 90-99 >/=100
<120 -3 [-3] pts
120-129 0 [0] pts
130-139 0 [0] pts

9
 140-159 2 [2] pts
>/=160 3 [3] pts

Note: When systolic and diastolic pressures provide different estimates for point scores, use the higher
number

Step 5

Diabetes
LDL Pts Chol Pts
No 0 [0]
Yes 4 [4]

Step 6

Smoker
LDL Pts Chol Pts
No 0 [0]
Yes 2 [2]

Step 7 (sum from steps 1-6)

Adding up the points

Age
LDL-C or Chol
HDL-C
Blood Pressure
Diabetes
Smoker
Point total

Step 8 (determine CHD risk from point total)

CHD Risk
LDL Pts Total 10 Yr CHD Risk Chol Pts Total 10 Yr CHD Risk
</=-2 1% [</=-2] [1%]
-1 2% [-1] [2%]
0 2% [0] [2%]
1 2% [1] [2%]
2 3% [2] [3%]
3 3% [3] [3%]
4 4% [4] [4%]
5 5% [5] [4%]
6 6% [6] [5%]
7 7% [7] [6%]
8 8% [8] [7%]
9 8% [9] [8%]
10 11% [10] [10%]
11 13% [11] [11%]
12 15% [12] [13%]

10
 13 17% [13] [15%]
14 20% [14] [18%]
15 24% [15] [20%]
16 27% [16] [24%]
>/=17 >/=32% [>/=17] [>/=27%]

Step 9 (compare to average person your age)

Comparative Risk
Age (Years) Average 10 Yr Average 10 Yr Low** 10 Yr
CHD Risk Hard* CHD CHD Risk
Risk
30-34 <1% <1% <1%
35-39 <1% <1% 1%
40-44 2% 1% 2%
45-49 5% 2% 3%
50-54 8% 3% 5%
55-59 12% 7% 7%
60-64 12% 8% 8%
65-69 13% 8% 8%
70-74 14% 11% 8%

* Hard CHD events exclude angina pectoris

** Low risk was calculated for a person the same age, optimal blood pressure, LDL-C 100-129 mg/dl or
cholesterol 160-199 mg/dl, HDL-C 45 mg/dl, for men or 55 mg/dl for women, non-smoker, no diabetes.

Risk estimates were derived from the experience of the Framingham Heart Study, a predominantly
Caucasian population in Massachusetts, USA

Key
Color Relative Risk
Green Very low
White Low
Yellow Moderate
Rose High
Red Very high

Electrocardiographic Diagnosis of Left Ventricular Hypertrophy (LVH)

Sokolow-Lyon index:
There are two criteria with these widely used indices:
* Sum of S wave in V1 and R wave in V5 or V6 >/= 3.5 mV (35 mm)
and/or
* R wave in aVL >/= 1.1 mV (11 mm)

Romhilt-Estes point score system:

Probable left ventricular hypertrophy is diagnosed if 4 points are present and definite left ventricular
hypertrophy is diagnosed if 5 or more points are present.

11
Criterion Points
Any limb R wave or S wave >/=2.0 mV (20 mm) 3
OR S in V1 or S in V2 >/= 3.0 mV (30 mm)
OR R in V5 or R in V6 >/= 3.0 mV (30 mm)
ST-T wave changes typical of LVH
Taking digitalis 1
Not taking digitalis 3
Left atrial abnormality 3
P terminal force in V1 is 1 mm or more in depth with a duration >/= 40 ms (0.04 sec)
Left axis deviation >/= -30 2
QRS duration >/= 90 ms 1
Intrinsicoid deflection in V5 or V6 >/= 50 ms (0.05 sec) * 1

* Intrinsicoid deflection is defined as interval between beginning of QRS interval and the peak of the R
wave

Cornell voltage criteria These more recent criteria are based upon echocardiographic correlative studies
designed to detect a left ventricular mass index >132 g/m2 in men and >109 g/m2 in women.
For men: S in V3 plus R in aVL >2.8 mV (28 mm)
For women: S in V3 + R in aVL >2.0 mV (20 mm)

Cornell voltage-duration measurement

QRS durationCornell Voltage > 2440 ms mV

Sensitivity and specificity for selected ECG criteria of LVH

Criterion Sensitivity (%) Specificity (%)

Sokolow Lyon Voltage 22 100
Cornell Voltage Criteria 42 96
Cornell Voltage Duration Criteria 51 95
RaVL > 11 mm 11 100
Romhilt-Estes > 4 points 54 85
Romhilt-Estes > 5 points 33 94

Revised Jones Criteria for Acute Rheumatic Fever (ARF)

A firm diagnosis requires that two major or one major and two minor criteria are satisfied, in addition to
evidence of recent streptococcal infection.

Major Criteria

1. Carditis: All layers of cardiac tissue are affected (pericardium, epicardium, myocardium,
endocardium) The patient may have a new or changing murmur, with mitral regurgitation being
the most common followed by aortic insufficiency.
2. Polyarthritis: Migrating arthritis that typically affects the knees, ankles, elbows and wrists. The
joints are very painful and symptoms are very responsive to anti-inflammatory medicines.
3. Chorea: Also known as Syndenhams chorea, or "St. Vitus dance". There are abrupt, purposeless
movements. This may be the only manifestation of ARF and is its presence is diagnostic. May also
include emotional disturbances and inappropriate behavior.
4. Erythema marginatum: A non-pruritic rash that commonly affects the trunk and proximal
extremities, but spares the face. The rash typically migrates from central areas to periphery, and
has well-defined borders.

12
 5. Subcutaneous nodules: Usually located over bones or tendons, these nodules are painless and firm.

Minor Criteria:

1. Fever
2. Arthralgia
3. Previous rheumatic fever or rheumatic heart disease
4. Acute phase reactants: Leukocytosis, elevated eritrosedimentation rate (ESR) and C-reactive
protein (CRP)
5. Prolonged P-R interval on electrocardiogram (ECG)

Evidence of preceding streptococcal infection: Any one of the following is considered adequate evidence
of infection:

Increased antistreptolysin O or other streptococcal antibodies

Positive throat culture for Group A beta-hemolytic streptococci
Positive rapid direct Group A strep carbohydrate antigen test
Recent scarlet fever.

New Diagnostic Criteria for Myocardial Infarction

Criteria for acute, evolving or recent MI

Either one of the following criteria satisfies the diagnosis for an acute, evolving or recent MI:
1) Typical rise and gradual fall (troponin) or more rapid rise and fall (CK-MB) of biochemical markers of
myocardial necrosis with at least one of the following:
a. ischemic symptoms;
b. development of pathologic Q waves on the ECG;
c. ECG changes indicative of ischemia (ST segment elevation or depression); or
d. coronary artery intervention (e.g., coronary angioplasty).
2) Pathologic findings of an acute MI.

Criteria for established MI

Any one of the following criteria satisfies the diagnosis for established MI:
1) Development of new pathologic Q waves on serial ECGs. The patient may or may not remember
previous symptoms. Biochemical markers of myocardial necrosis may have normalized, depending on the
length of time that has passed since the infarct developed.
2) Pathologic findings of a healed or healing MI.

Diagnostic Criteria for Acute Pericarditis

Diagnostic criteria include the following:

1. pericarditic typical chest pain,

2. pericardial friction rubs,
3. widespread ST segment elevation or PR depressions not previously reported, and
4. new or worsening pericardial effusion.

A clinical diagnosis of acute pericarditis is made when at least 2 of these criteria are present.

13
A clinical diagnosis of myopericarditis is performed in patients with diagnostic criteria for acute
pericarditis and 1 of the following features:

1. evidence of elevated cardiac enzymes (creatine kinase-MB fraction, or troponin I or T) or

2. new onset of focal or diffuse depressed left ventricular function by echocardiography.

Causes of Syncope

Cardiac causes
Structural cardiac or cardiopulmonary disease (aortic stenosis, mitral stenosis, pulmonary stenosis,
left atrial myxoma, aortic dissection, acute myocardial infarction, cardiac tamponade, pulmonary
embolism, obstructive cardiomyopathy)
Cardiac arrhythmias (tachyarrhythmias, bradyarrhythmias)
Neurally mediated syncopal syndrome (includes neurocardiogenic or vasovagal syncope, carotid
sinus syncope, and situational syncope)
Orthostatic (or postural) hypotension
Metabolic causes
Hypoxia
Hypoglycaemia
Hyperventilation
Psychiatric causes
Somatisation disorders
Hysteria
Panic
Fright
Neurological causes
Seizure disorders
Transient ischaemic attacks
Subclavian steal syndrome
Normal pressure hydrocephalus

Wells Clinical Prediction Rule for Pulmonary Embolism and Deep Venous Thrombosis

Wells Clinical Prediction Rule for Pulmonary Embolism (PE)

Clinical feature Points

Clinical symptoms of DVT 3
Other diagnosis less likely than PE 3
Heart rate greater than 100 beats per minute 1.5
Immobilization or surgery within past 4 weeks 1.5
Previous DVT or PE 1.5
Hemoptysis 1
Malignancy 1
Total points

PE = pulmonary embolism; DVT = deep venous thrombosis.

Risk score interpretation (probability of PE):

>6 points: high risk (78.4%);

2 to 6 points: moderate risk (27.8%);
<2 points: low risk (3.4%)

14
Wells Clinical Prediction Rule for Deep Venous Thrombosis (DVT)

Clinical feature Points

Active cancer (treatment within 6 months, or palliation) 1
Paralysis, paresis, or immobilization of lower extremity 1
Bedridden for more than 3 days because of surgery (within 4 1
weeks)
Localized tenderness along distribution of deep veins 1
Entire leg swollen 1
Unilateral calf swelling of greater than 3 cm (below tibial 1
tuberosity)
Unilateral pitting edema 1
Collateral superficial veins 1
Alternative diagnosis as likely as or more likely than DVT -2
Total points

DVT = deep venous thrombosis.

Risk score interpretation (probability of DVT):

>/=3 points: high risk (75%);

1 to 2 points: moderate risk (17%);
<1 point: low risk (3%).

Indications and Contraindications for Tilt Table Testing

Indications
Recurrent syncope or single syncopal episode accompanied by physical injury or motor vehicle
crash or occurring in a high risk setting (for example, pilot, surgeon, commercial vehicle driver)
and no evidence of structural cardiovascular disease; or presence of structural cardiovascular
disease but other causes of syncope ruled out by diagnostic testing
Syncope induced by or associated with exercise
Further evaluation of patients in whom an apparent specific cause of syncope has been established
(for example, asystole, high atrioventricular block) but susceptibility to neurocardiogenic syncope
may affect treatment plan
Contraindications
Syncope with severe left ventricular outflow obstruction (for example, aortic stenosis)
Syncope in presence of severe mitral stenosis
Syncope in setting of known critical proximal coronary artery disease
Syncope in setting of known critical cerebrovascular disease

TIMI Risk Score for ST-Elevation Myocardial Infarction (STEMI)

The TIMI risk score, based upon data from 15,000 patients with an ST segment elevation myocardial
infarction eligible for fibrinolytic therapy, is a simple arithmetic sum of eight independent predictors of
mortality.

TIMI Risk Score for STEMI

Historical
Age 65-74 2 points
>/= 75 3 points
DM/HTN or Angina 1 point

15
Exam
SBP < 100 3 points
HR > 100 2 points
Killip II-IV 2 points
Weight < 67 kg 1 point
Presentation
Anterior STE or LBBB 1 point
Time to rx > 4 hrs 1 point
Risk Score = Total (0-14)

DM, diabetes mellitus; HTN, hypertension; SBP, systolic blood pressure; HR, heart rate;
STE, ST elevation; LBBB, left bundle branch block; and rx, treatment.

Risk Score Odds of death by 30D*

0 0.1 (0.1-0.2)
1 0.3 (0.2-0.3)
2 0.4 (0.3-0.5)
3 0.7 (0.6-0.9)
4 1.2 (1.0-1.5)
5 2.2 (1.9-2.6)
6 3.0 (2.5-3.6)
7 4.8 (3.8-6.1)
8 5.8 (4.2-7.8)
>8 8.8 (6.3-12)
* referenced to average mortality (95% confidence intervals)

Indications and Contraindications for Liver Transplantation

Indications for liver transplantation

1- Acute liver failure

Acute hepatitis A
Acute hepatitis B
Drug/toxin hepatotoxicity

2- Cirrhosis from chronic liver diseases

Chronic hepatitis B virus and chronic hepatitis C virus infection

Alcoholic liver disease
Autoimmune hepatitis
Cryptogenic liver disease
Primary biliary cirrhosis and primary sclerosing cholangitis
Secondary biliary cirrhosis

3- Metabolic disorders

Alpha-1 antitrypsin deficiency

Hereditary hemochromatosis
Wilsons disease

16
 Glycogen-storage disorders
Type 1 hyperoxaluria
Familial homozygous hypercholesterolemia

4- Malignancy

Primary hepatic cancer: hepatocellular carcinoma and cholangiocarcinoma

Metastatic: carcinoid tumors and islet cell tumors

5- Miscellaneous

Polycystic liver disease

Budd-Chiari syndrome

Contraindications to liver transplantation

1- Absolute contraindications

Brain death
Extrahepatic malignancy
Active uncontrolled infection
Active alcoholism and substance abuse
AIDS
Severe cardiopulmonary disease
Uncontrolled sepsis
Inability to comply with medical regimen
Lack of psychosocial support
Anatomic abnormalities precluding liver transplantation
Compensated cirrhosis without complications (Child-Turcotte-Pugh score, 56)

2- Relative contraindications

Advanced age
Cholangiocarcinomaa
HIV infectiona
Portal vein thrombosis
Psychologic instability

a
Transplantation for cholangiocarcinoma is undergoing study using protocols with strict selection criteria
and use of chemotherapy and radiation. Transplantation for HIV infection without AIDS also is undergoing
study as part of a National Institutes of Health protocol

Kings College Hospital Criteria for Liver Transplantation in Fulminant Hepatic Failure

Acetaminophen-induced disease

Arterial pH <7.3 (irrespective of the grade of encephalopathy)

or

17
Grade III or IV encephalopathy, and
Prothrombin time >100 seconds, and
Serum creatinine >3.4mg/dl (301 mol/L)

All other causes of fulminant hepatic failure

Prothrombin time >100 seconds (irrespective of the grade of encephalopathy)

Or
Any three of the following variables (irrespective of the grade of encephalopathy)
1. Age <10 years or >40 years
2. Etiology: non-A, non-B hepatitis, halothane hepatitis, idiosyncratic drug reactions
3. Duration of jaundice before onset of encephalopathy >7 days
4. Prothrombin time >50 seconds
5. Serum bilirrubin >18 mg/dl (308 mol/L)

Histological Scoring System for Nonalcoholic Fatty Liver Disease (NAFLD)

Components of NAFLD Activity Score (NAS) and Fibrosis Staging

NAS Components (see scoring interpretation)

Item Score Extent Definition and Comment
Steatosis 0 <5% Refers to amount of surface area involved by
steatosis as evaluated on low to medium power
examination; minimal steatosis (<5%) receives a
score of 0 to avoid giving excess weight to biopsies
with very little fatty change
1 5-33%
2 >33-66%
3 >66%
Lobular 0 No foci Acidophil bodies are not included in this assessment,
Inflammation nor is portal inflammation
1 <2 foci/200x
2 2-4 foci/200x
3 >4 foci/200x
Hepatocyte 0 None
Ballooning 1 Few balloon cells The term "few" means rare but definite ballooned
hepatocytes as well as cases that are diagnostically
borderline
2 Many Most cases with prominent ballooning also had
cells/prominent Mallory's hyalin, but Mallory's hyaline is not scored
ballooning separately for the NAS
Fibrosis Stage (Evaluated separately from NAS)
Fibrosis 0 None
1 Perisinusoidal or
periportal
1A Mild, zone 3, "delicate" fibrosis
perisinusoidal
1B Moderate, zone 3, "dense" fibrosis
perisinusoidal
1C Portal/periportal This category is included to accommodate cases with
portal and/or peri portal fibrosis without
accompanying pericellular/perisinusoidal fibrosis
2 Perisinusoidal and

18
 portal/periportal
3 Bridging fibrosis
4 Cirrhosis

Total NAS score represents the sum of scores for steatosis, lobular inflammation, and ballooning, and
ranges from 0-8. Diagnosis of NASH (or, alternatively, fatty liver not diagnostic of NASH) should be made
first, then NAS is used to grade activity. In the reference study, NAS scores of 0-2 occurred in cases largely
considered not diagnostic of NASH, scores of 3-4 were evenly divided among those considered not
diagnostic, borderline, or positive for NASH. Scores of 5-8 occurred in cases that were largely considered
diagnostic of NASH.

Severity Criteria for Acute Pancreatitis

Ranson Criteria to Predict Severity of Acute Pancreatitis

1. When three or more of the following are present on admission, a severe course complicated by
pancreatic necrosis can be predicted with a sensitivity of 60-80%:
Age over 55 years.
White blood cell count over 16,000/uL.
Blood glucose over 200 mg/dL.
Serum lactate dehydrogenase (LDH) over 350 units/L.
Aspartate aminotransferase (AST, SGOT) over 250 units/L.
2. Development of the following in the first 48 hours indicates a worsening prognosis:
Hematocrit drop of more than ten percentage points.
Blood urea nitrogen (BUN) rise greater than 5 mg/dL.
Arterial PO2 of less than 60 mm Hg.
Serum calcium of less than 8 mg/dL.
Base deficit over 4 meq/L.
Estimated fluid sequestration of more than 6 L.
3. Mortality rates correlate with the number of criteria present:

Number of criteria Mortality rate

0-2 1%
3-4 16%
5-6 40%
7-8 100%

Balthazar CT severity index for acute pancreatitis.

CT Grade Points Necrosis Additional Severity Mortality

(%) Points Index Rate (%)
A Normal pancreas 0 0 0 0 0
B Pancreatic 1 0 0 1 0
enlargement
C Pancreatic 2 < 30 2 4 0
inflammation and/or
peripancreatic fat
D Single 3 30-50 4 7 > 17
peripancreatic fluid
collection
E Two or more fluid 4 > 50 6 10
collections or

19
retroperitoneal air

Diagnostic Criteria for Autoimmune Pancreatitis

Diagnostic Criteria for Autoimmune Pancreatitis by the Japan Pancreas Society

Findings on Imaging Radiography Serologic and Histologic Findings (One Required)

(One Required)
Cross-sectional ERCP or MRCP Serologic Analysis Pancreatic-Biliary Nongastrointestinal
Imaging Histologic Analysis Histologic Analysis
Diffusely enlarged Segmental pancreatic Elevated serum IgG4 Periductal lympho- Tubulointerstitial
pancreas ductal narrowing level plasmacytic nephritis with immune
infiltration or fibrosis deposits within
tubular basement
membranes
Enhanced Focal pancreatic Elevated serum IgG Obliterative phlebitis Pulmonary interstitial
peripheral rim of ductal narrowing or gamma globulin lymphoplasmacytic
hypoattenuation level infiltration with IgG4-
halo positive plasma cells
Low-attenuation Diffuse pancreatic Presence of ALA, IgG4-positive plasma Chronic sialadenitis
mass in head of ductal narrowing ACA II, ASMA, or cells in tissue with IgG4-positive
pancreas ANA plasma cells

Criteria were modified from those of the Japan Pancreas Society. ERCP denotes endoscopic retrograde
cholangiopancreatography, MRCP magnetic resonance cholangiopancreatography, ALA antilactoferrin
antibody, ACA II anti-carbonic anhydrase II antibody, ASMA anti-smooth-muscle antibody, and ANA
antinuclear body.

The presence of tissue IgG4-positive cells is not necessarily abnormal, but an increased number of
infiltrating IgG4-positive plasma cells is abnormal.

Diagnostic Criteria for Autoimmune Pancreatitis in Asan Medical Center

Inclusion Criteria

Criterion I. Pancreatic imaging (essential)

1. CT: Diffuse enlargement (swelling) of pancreas, and

2. ERCP: Diffuse or segmental irregular narrowing of main pancreatic duct

Criterion II. Laboratory findings

1. elevated levels of IgG and/or IgG4. or

2. detected autoantibodies

Criterion III. Histopathologic findings: Fibrosis and lymphoplasmacytic infiltration

Criterion IV. Response to the steroid

20
Definite diagnosis: Criterion I and any of criterion II-IV

Diagnostic Criteria for Autoimmune Pancreatitis by Italian Group

Diagnostic criteria

1. Histology and cytology

2. The association with other postulated autoimmune disease
3. Response to the steroid therapy

Diagnosis of Spontaneous Bacterial Peritonitis (SBP)

Indications for diagnostic paracentesis.

Cirrhotic patients with ascites at admission

Cirrhotic patients with ascites and signs or symptoms of infection: fever, leukocytosis, abdominal
pain
Cirrhotic patients with ascites who present with a clinical condition that is deteriorating during
hospitalization: renal function impairment, hepatic encephalopathy, gastrointestinal bleeding
Patients with new-onset ascites

Analysis of Peritoneal Fluid

Test and Ascitic-Fluid Comments

Container
Albumin Differential diagnosis of ascites according to the serumascites albumin
gradient
Cell Cell count and differential count
Culture Aerobic- and anaerobic-culture

Additional Analyses of Ascitic Fluid

Test and Ascitic-Fluid Comments

Container
Tube without additives
Total protein
Lactate dehydrogenase
Glucose
Carcinoembryonic antigen
Alkaline phosphatase
Amylase
Triglyceride
Syringe or evacuated container
Cytology
Mycobacterial culture
Values >1 g/dl suggest secondary peritonitis instead of SBP
Values greater than the upper limit of normal for serum suggest secondary
peritonitis instead of SBP
Values <50 mg/dl suggest secondary peritonitis instead of SBP
Values >5 ng/ml suggest hollow viscus perforation
Values >240 U/liter suggest hollow viscus perforation
Values markedly elevated (often >2000 U/liter or five times serum levels)
in patients with pancreatic ascites or hollow viscus perforation
Values >200 mg/dl suggest chylous ascites
Sensitivity increased if three samples submitted and promptly evaluated
Sensitivity only 50%

21
Differential Diagnosis of Ascites According to the SerumAscites Albumin Gradient

Gradient >1.1 g/dl (portal hypertension) Gradient <1.1 g/dl

Cirrhosis Peritoneal carcinomatosis
Alcoholic hepatitis Tuberculous peritonitis
Cardiac ascites Pancreatic ascites
Portal-vein thrombosis Biliary ascites
Budd-Chiari syndrome Nephrotic syndrome
Liver metastases Serositis

The diagnosis of SBP is suggested by a polymorphonuclear (PMN) cell count in excess of 250 cells per
cubic millimeter in the absence of evidence of an alternative source of infection (secondary peritonitis),
such as viscus perforation or intraabdominal abscess.

Determination of total protein, lactate dehydrogenase, and glucose levels in ascitic fluid may aid in the
differentiation between SBP and secondary peritonitis. Culture is used to confirm the diagnosis of SBP.

Appropriate Indications for Upper Gastrointestinal Endoscopy (UGE)

1. Uncomplicated dyspepsia
2. Frequent symptoms (>= 2/wk) suggesting gastroesophageal reflux disease (GERD) or history of
reflux-associated mucosal disease of the esophagus, without alarm symptoms and without Barrett's
esophagus
3. Known Barrett's esophagus, without alarm symptoms
4. Atypical chest pain
5. Alarm symptoms: recent upper GI bleeding, esophageal dysphagia, unexplained weight loss, iron
deficiency anemia
6. Risk factors and pre-malignant conditions of the UGI tract: pernicious anemia, atrophic gastritis,
status post-gastrectomy, gastric polyps, familial adenomatous polyposis
7. Miscellaneous indications: assess healing of benign gastric ulcer, follow-up of
sclerotherapy/banding, suspected malignant lesion on UGI series, suspected malabsorption
syndrome

Diagnostic Criteria for Zollinger-Ellison Syndrome (ZES)

Diagnostic criteria for ZES include the following:

1. Elevated levels of Basal Acid Output (BAO), greater than 15 mEq in unoperated patients and
greater than 5 mEq if previous acid-reducing surgery has been performed;
2. Elevated level of fasting serum gastrin (>100 pg/mL until 1994, >200 pg/mL since 1994);
3. Abnormal results from stimulation testing with secretin (an increase of >200 pg/mL postinjection)
or with calcium (an increase >395 pg/mL);
4. Positive histologic confirmation of gastrinoma; or
5. A combination of these criteria.

The tests used most commonly to establish a diagnosis of ZES are the fasting serum gastrin concentration
and BAO evaluation. Measurement of gastric pH is important to exclude achlorhydria as a cause of

22
secondary hypergastrinemia. Patients taking Proton Pump Inhibitors (PPIs), those who have undergone
massive small bowel resection, or those who have renal insufficiency, G-cell hyperplasia, or gastric outlet
obstruction may have gastrin levels between 150 and 1000 pg/mL Hence, for patients with suspected ZES
with an equivocal fasting serum gastrin concentration, a secretin stimulation test should be performed.

CDC Diagnostic Criteria for the Diagnosis of Pelvic Inflammatory Disease (PID)

Minimal criteria*

Lower abdominal tenderness

Uterine/adnexal tenderness
Cervical motion tenderness

Additional criteria

Oral temperature > 38.3C (101F)

Abnormal cervical or vaginal mucopurulent discharge
Presence of white blood cells (WBCs) on saline microscopy of vaginal secretions
Elevated erythrocyte sedimentation rate
Elevated C-reactive protein level
Laboratory documentation of cervical infection with Neisseria gonorrhoeae or Chlamydia
trachomatis

Definitive criteria

Histopathologic evidence of endometritis on endometrial biopsy

Transvaginal sonography or magnetic resonance imaging techniques showing thickened, fluid-
filled tubes with or without free pelvic fluid or tubo-ovarian complex
Laparoscopic abnormalities consistent with PID

PID, pelvic inflammatory disease

* Empiric treatment is indicated in sexually active women considered at risk for PID if all three findings
are present.

Amsel's Diagnostic Criteria for Bacterial Vaginosis

Three of four criteria must be met; establishes accurate diagnosis of bacterial vaginosis in 90 percent of
affected women.

Homogeneous vaginal discharge (color and amount may vary)

Amine (fishy) odor when potassium hydroxide solution is added to vaginal secretions (commonly
called the "whiff test")
Presence of clue cells (greater than 20%) on microscopy*
Vaginal pH greater than 4.5

* Highly significant criterion.

Relative Potencies of Systemic Glucocorticoids.

23
Glucocorticoid Approximate Equivalent dose (mg) Half-life (Biologic) hours
Short-Acting
Cortisone 25 8-12
Hydrocortisone 20 8-12
Intermediate-Acting
Methylprednisolone 4 18-36
Prednisolone 5 18-36
Prednisone 5 18-36
Triamcinolone 4 18-36
Long-Acting
Betamethasone 0.6 - 0.75 36-54
Dexamethasone 0.75 36-54

Clinical Conditions Associated with Disseminated Intravascular Coagulation (DIC)

1. Sepsis/severe infection (any microorganism)

2. Trauma (e.g., polytrauma, neurotrauma, fat embolism)
3. Organ destruction (e.g., severe pancreatitis)
4. Malignancy
solid tumors
myeloproliferative/lymphoproliferative malignancies
5. Obstetrical calamities
amniotic fluid embolism
abruptio placentae
6. Vascular abnormalities
Kasabach-Merritt syndrome
large vascular aneurysms
7. Severe hepatic failure
8. Severe toxic or immunologic reactions
snake bites
recreational drugs
transfusion reactions
transplant rejection

Diagnostic Criteria for Essential Thrombocytopaenia (ET)

Polycythemia Vera Study Group (PVSG) Diagnostic Criteria for Essential Thrombocytopaenia (ET)

All of the following criteria must be fulfilled to make a diagnosis of ET

1. Platelet count greater than 600 x 109/L

2. Hematocrit less than 40 or normal red blood cell mass
3. Stainable iron in the marrow or normal RBC mean corpuscular volume (If these measurements
suggest iron deficiency, polycythemia vera cannot be excluded unless a trial of iron therapy fails to
increase the red blood cell mass into the polycythemic range.)
4. No Philadelphia chromosome or bcr/abl gene rearrangement
5. Collagen fibrosis of the bone marrow absent or less than one third of the biopsy area without both
marked splenomegaly and a leukoerythroblastic blood film
6. No cytogenetic or morphologic evidence for a myelodysplastic syndrome

24
 7. No cause for a reactive thrombocytosis

WHO Diagnostic Criteria for Essential Thrombocytopaenia (ET)

Positive criteria

1. Sustained platelet count > 600x 109/l

2. Bone marrow biopsy specimen showing proliferation mainly of the megakaryocytic lineage with
increased numbers of enlarged, mature megakaryocytes

Criteria of exclusion

1. No evidence of polycythaemia vera (PV)

Normal red cell mass or Hb <18.5 g/dl in men, 16.5g/dl in women
Stainable iron in marrow, normal serum ferritin or normal mean corpuscular volume (MCV)
If the former is not met, failure of iron trial to increase red cell mass or hemoglobin levels to the
PV range
2. No evidence of CML
No evidence of Philadelphia chromosome and no BCR/ABL fusion gene
3. No evidence of idiopathic myelofibrosis
Collagen fibrosis absent
Reticulin fibrosis minimal or absent
4. No evidence of myelodysplastic syndrome
No del(5q), t(3;3)(q21;26),inv(3)(q21q26)
No significant granulocytic dysplasia; few, if any, micromegakaryocytes
5. No evidence that thrombocytosis is reactive due to:
Underlying inflammation or infection
Underlying neoplasm
Prior splenectomy

Wagner and the University of Texas Wound Classification Systems of Diabetic Foot Ulcers

Wagner Classification of Diabetic Foot Ulcers

Grade 0: No ulcer in a high risk foot.

Grade 1: Superficial ulcer involving the full skin thickness but not underlying tissues.
Grade 2: Deep ulcer, penetrating down to ligaments and muscle, but no bone involvement or abscess
formation.
Grade 3: Deep ulcer with cellulitis or abscess formation, often with osteomyelitis.
Grade 4: Localized gangrene.
Grade 5: Extensive gangrene involving the whole foot.

University of Texas Wound Classification System of Diabetic Foot Ulcers

Grade I-A: non-infected, non-ischemic superficial ulceration

Grade I-B: infected, non-ischemic superficial ulceration
Grade I-C: ischemic, non-infected superficial ulceration
Grade I-D: ischemic and infected superficial ulceration

Grade II-A: non-infected, non-ischemic ulcer that penetrates to capsule or bone

Grade II-B: infected, non-ischemic ulcer that penetrates to capsule or bone

25
Grade II-C: ischemic, non-infected ulcer that penetrates to capsule or bone
Grade II-D: ischemic and infected ulcer that penetrates to capsule or bone

Grade III-A: non-infected, non-ischemic ulcer that penetrates to bone or a deep abscess
Grade III-B: infected, non-ischemic ulcer that penetrates to bone or a deep abscess
Grade III-C: ischemic, non-infected ulcer that penetrates to bone or a deep abscess
Grade III-D: ischemic and infected ulcer that penetrates to bone or a deep abscess

Diagnosis of Gestational Diabetes Mellitus (GDM)

Screening for gestational diabetes mellitus

1. 50-g oral glucose load, administered between the 24th and 28th weeks, without regard to time of
day or time of last meal. Universal blood glucose screening is indicated for patients who are of
Hispanic, African, Native American, South or East Asian, Pacific Island, or Indigenous Australian
ancestry. Other patients who have no known diabetes in first-degree relatives, are under 25 years
of age, have normal weight before pregnancy, and have no history of abnormal glucose
metabolism or poor obstetric outcome do not require routine screening.
2. Venous plasma glucose measure 1 hour later.
3. Value of 130 mg/dL (7.2 mmol/L) or above in venous plasma indicates the need for a full
diagnostic glucose tolerance test.

Diagnosis of gestational diabetes mellitus

The diagnosis of GDM is based on an OGTT. Diagnostic criteria for the 100-g OGTT are derived from the
original work of OSullivan and Mahan modified by Carpenter and Coustan. Alternatively, the diagnosis
can be made using a 75-g glucose load and the glucose threshold values listed for fasting, 1 h, and 2 h;
however, this test is not as well validated as the 100-g OGTT.

Diagnosis of GDM with a 100-g or 75-g glucose load

mg/dl mmol/l
100-g glucose load
Fasting 95 5.3
1-h 180 10.0
2-h 155 8.6
3-h 140 7.8
75-g glucose load
Fasting 95 5.3
1-h 180 10.0
2-h 155 8.6

Two or more of the venous plasma concentrations must be met or exceeded for a positive diagnosis. The
test should be done in the morning after an overnight fast of between 8 and 14 h and after at least 3 days of
unrestricted diet (>150 g carbohydrate per day) and unlimited physical activity. The subject should remain
seated and should not smoke throughout the test.

Pharmacokinetics of Insulin Preparations

26
 Time of Action
Preparation Onset, h Peak, h Effective Duration, h
Short-acting, subcutaneous
Lispro <0.25 0.51.5 34
Aspart <0.25 0.51.5 34
Glulisine <0.25 0.51.5 34
Regular 0.51.0 23 46
Short-acting, inhaled
Inhaled regular insulin <0.25 0.51.5 46
Long-acting
NPH 14 610 1016
Detemir 14 a 1220
a
Glargine 14 24
Insulin Combinations
75/2575% protamine lispro, 25% lispro <0.25 1.5 hb Up to 1016
70/3070% protamine aspart, 30% aspart <0.25 1.5 hb Up to 1016
50/5050% protamine lispro, 50% lispro <0.25 1.5 hb Up to 1016
70/3070% NPH, 30% regular insulin 0.51 Dual 1016
50/5050% NPH, 50% regular insulin 0.51 Dual 1016
a
Glargine has minimal peak activity; detemir has some peak activity at 614 h.
b
Dual: two peaks; one at 23 h; the second several hours later.

International Clinical Diabetic Retinopathy and Diabetic Macular Edema Disease Severity Scales

International Clinical Diabetic Retinopathy Disease Severity Scale

Proposed Disease Severity Level Findings Observable upon Dilated Ophthalmoscopy
No apparent retinopathy No abnormalities

27
Mild nonproliferative diabetic retinopathy
Moderate nonproliferative diabetic retinopathy
Severe nonproliferative diabetic retinopathy
Proliferative diabetic retinopathy
Microaneurysms only
More than just microaneurysms but less than severe
NPDR
Any of the following:
More than 20 intraretinal hemorrhages in each of four
quadrants
Definite venous beading in two or more quadrants
Prominent IRMA in one or more quadrants
And no signs of proliferative retinopathy
One or both of the following:
Neovascularization
Vitreous/preretinal hemorrhage

IRMA = intraretinal microvascular abnormalities; NPDR = nonproliferative diabetic retinopathy

International Clinical Diabetic Macular Edema Disease Severity Scale

Proposed Disease Severity Level Findings Observable upon Dilated Ophthalmoscopy
Diabetic macular edema apparently absent No apparent retinal thickening or hard exudates in
Diabetic macular edema apparently present posterior pole
Some apparent retinal thickening or hard exudates in
posterior pole
If diabetic macular edema is present, it can be categorized as follows:
Proposed Disease Severity Level Findings Observable upon Dilated
Ophthalmoscopy*
Diabetic macular edema present . Mild diabetic macular edema: Some retinal thickening
or hard exudates in posterior pole but distant from the
center of the macula
Moderate diabetic macular edema: Retinal thickening or hard exudates approaching the center of the
macula but not involving the center
Severe diabetic macular edema: Retinal thickening or hard exudates involving the center of the macula . .

* Hard exudates are a sign of current or previous macular edema. Diabetic macular edema is defined as
retinal thickening; this requires a three-dimensional assessment that is best performed by dilated
examination using slit-lamp biomicroscopy and/or stereo fundus photography.

Diagnosis and Indications for Treatment of Molluscum Contagiosum

Molluscum contagiosum is generally a benign disease consisting of pearly, flesh-colored, umbilicated skin
lesions 2 to 5 mm in diameter with a characteristic dimple at the center

The diagnosis of molluscum contagiosum is usually made by the characteristic appearance of the lesions.
When necessary, histologic or electron microscopic (EM) examination can confirm the clinical diagnosis.
Hematoxylin and eosin staining reveals keratinocytes containing eosinophilic cytoplasmic inclusion bodies.
EM of such biopsies would reveal typical brick-shaped poxvirus particles, similar to those of smallpox. EM
also shows some infected cells that might look normal using light microscopy.

Reasons to treat molluscum contagiosum include:

28
 1. alleviating discomfort, including itching;
2. cosmetic reasons;
3. social stigma associated with many visible lesions;
4. limiting its spread to other areas of the body and to other people;
5. preventing scarring and secondary infection;
6. preventing trauma and bleeding of lesions.

Diagnosis of Multiple Endocrine Neoplasia Syndromes

Syndrome Mutated gene Manifestations

MEN1 MEN1 Primary hyperparathyroidism (usually four-gland
hyperplasia), anterior pituitary adenomas, tumors of
endocrine pancreas and duodenum, foregut
carcinoids
MEN subtype 2A RET proto-oncogene Medullary thyroid cancer, pheochromocytoma,
primary hyperparathyroidism (usually single
adenoma), cutaneous lichen amyloidosis,
Hirschsprung disease
MEN subtype 2B RET proto-oncogene Medullary thyroid cancer, pheochromocytoma,
marfanoid body habitus, facial features resulting
from mucosal neuromas, ganglioneuromatosis of the
gastrointestinal tract
Familial medullary RET proto-oncogene Medullary thyroid cancer in at least four family
thyroid cancer members, with documented absence of other
endocrinopathies
Hyperparathyroidism-jaw HRPT2 Primary hyperparathyroidism (usually single
tumor syndrome adenoma), ossifying fibromas of maxilla or
mandible, renal cysts and hamartomas, 15% risk of
parathyroid carcinoma
Familial isolated MEN1, HRPT2, CASR, Nonsyndromic primary hyperparathyroidism
hyperparathyroidism other
Familial hypocalciuric CASR Benign hypercalcemia; medical management only
hypercalcemia
von Hippel-Lindau VHL Pheochromocytoma, retinal and central nervous
syndrome (VHL) system hemangioblastoma, renal cysts and clear cell
carcinoma, pancreatic cysts and islet cell tumors,
endolymphatic sac tumors, papillary cystadenomas
of the epididymis and broad ligament
Familial SDHB, SDHC, SDHD Multiple paragangliomas and pheochromocytoma
pheochromocytoma/
paraganglioma syndrome
Neurofibromatosis type I NF1 Pheochromocytoma, characteristic physical features
(eg, caf-au-lait spots, neurofibromas, axillary and
inguinal freckling)
Cowden syndrome PTEN Nonmedullary thyroid cancer (usually follicular
rather than papillary); benign and malignant tumors
of skin, oral mucosa, breast, and uterus
Familial adenomatous APC Hundreds of adenomatous colon polyps, colon
polyposis cancer, cribriform morular variant of papillary
thyroid cancer
Carney complex PRKAR1A Endocrine tumors (including thyroid, pituitary,

29
 primary pigmented nodular adrenocortical disease),
characteristic skin pigmentation, myxomas,
melanotic schwannomas
Familial nonmedullary Unknown Nonsyndromic nonmedullary thyroid cancer
thyroid cancer

Criteria for Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

Hypotonic hyponatremia
Urine osmolality >100 mOsm per kg (100 mmol per kg)
Absence of extracellular volume depletion
Normal thyroid and adrenal function
Normal cardiac, hepatic and renal function

Diagnostic Criteria for Cholangitis

The diagnostic criteria for cholangitis are:

a. fever or abdominal pain in the right upper quadrant;
b. endoscopic or radiologic (sonography or CT) evidence of biliary tract obstruction owing to stones,
stricture, or tumor; and
c. laboratory evidence of hyperbilirubinemia and elevated alkaline phosphatase.

Appropriate Indications for Colonoscopy

1. Iron-deficiency anemia (malabsorption syndrome excluded)

2. Hematochezia (without Inflammatory Bowel Disease - IBD).
3. Uncomplicated lower abdominal pain of at least 2 months'duration, without known inflammatory
bowel disease, without anemia and without Fecal Occult Blood Test (FOBT) positive.
4. Change in bowel habits (predominantly constipation), of at least 2 months'duration, without
known inflammatory bowel disease, without anemia or FOBT-positive stools and without pain.
5. Uncomplicated diarrhea (infectious or malabsorption origin excluded and without known IBD).
No anemia. No bleeding. No radio-frequency (RF) for Colorectal (CR) cancer.
6. Evaluation of known ulcerative colitis (UC)
7. Evaluation of known Crohn's disease (CD)
8. Screening for colorectal cancer in patients with known inflammatory ulcerative colitis
9. Screening for colorectal cancer in patients with known Crohn's disease
10. Surveillance after colonic polypectomy or curative intent resection of colorectal cancer
11. Screening for colorectal cancer
12. Miscellaneous indications: lesion at recent barium enema or sigmoidoscopy, preoperative
colonoscopy, FOBT-positive stools, fulminant colitis, acute diverticulitis, endometriosis,
unexplained weight loss

Diagnostic Criteria of Hepatorenal Syndrome (HRS)

Major criteria
1. Low glomerular filtration rate, as indicated by serum creatinine greater than 1.5 mg/dl or 24-hour
creatinine clearance lower than 40 ml/minute

30
 2. Absence of shock, ongoing bacterial infection, fluid losses and current treatment with nephrotoxic
drugs
3. No sustained improvement in renal function (decrease in serum creatinine to 1.5 mg/dl or less or
increase in creatinine clearance to 40 ml/minute or more) following diuretic withdrawal and
expansion of plasma volume with 1.5 l of a plasma expander
4. Proteinuria lower than 500 mg/day and no ultrasonographic evidence of obstructive uropathy or
parenchymal renal disease
Additional criteria
1. Urine volume lower than 500 ml/day
2. Urine sodium lower than 10 mEq/l
3. Urine osmolality greater than plasma osmolality
4. Urine red blood cells less than 50 per high-power field
5. Serum sodium concentration lower than 130 mEq/l
All major criteria must be present for the diagnosis of hepatorenal syndrome. Additional criteria are not
necessary for the diagnosis, but provide supportive evidence.

Clinical types of hepatorenal syndrome

Type I: Rapid and progressive impairment of renal function as defined by a doubling of the initial serum
creatinine to a level higher than 2.5 mg/dl or a 50% reduction of the initial 24-hour creatinina clearance to a
level lower than 20 ml/minute in less than 2 weeks
Type II: Impairment in renal function (serum creatinine 41.5 mg/dl) that does not meet the criteria of type I

Diagnostic Criteria for the Hepatopulmonary Sndrome (HPS)

Variable Criterion
Oxygenation defect Partial pressure of oxygen <80 mm Hg or alveolararterial oxygen gradient
15 mm Hg while breathing ambient air
Pulmonary vascular Positive findings on contrast-enhanced echocardiography or abnormal uptake
dilatation in the brain (>6%) with radioactive lung-perfusion scanning
Liver disease Portal hypertension (most common) with or without cirrhosis
Degree of severity
Mild * Alveolararterial oxygen gradient 15 mm Hg, partial pressure of oxygen
80 mm Hg
Moderate * Alveolararterial oxygen gradient 15 mm Hg, partial pressure of oxygen
60 to <80 mm Hg
Severe * Alveolararterial oxygen gradient 15 mm Hg, partial pressure of oxygen
50 to <60 mm Hg
Very severe * Alveolararterial oxygen gradient 15 mm Hg, partial pressure of oxygen
<50 mm Hg (<300 mm Hg while the patient is breathing 100% oxygen)

All criteria were determined by means of positive contrast-enhanced echocardiography (i.e., microbubble
opacification of the left heart chambers three to six cycles after right atrial passage). The abbreviated
formula for the alveolararterial gradient is as follows:

PAO2PaO2 = (FIO2 [PatmPH2O] [PaCO2/0.8]) PaO2,

where PAO2 denotes partial pressure of alveolar oxygen, PaO2 partial pressure of arterial oxygen, FIO2
fraction of inspired oxygen, Patm atmospheric pressure, PH2O partial pressure of water vapor at body
temperature, and PaCO2 partial pressure of arterial carbon dioxide (0.8 corresponds to the standard gas-
exchange respiratory ratio at rest); the normal range is 4 to 8 mm Hg (0.5 to 1.1 kPa). The normal range for
the partial pressure of oxygen is 80 to 100 mm Hg (10.7 to 13.3 kPa) at sea level, while the patient is at rest
and breathing ambient air. For patients older than 64 years of age, a value of 70 mm Hg (9.3 kPa) for PaO2

31
or 20 mm Hg for the alveolar-arterial gradient is often used. Ambient air is the respired gas unless
otherwise indicated. To convert millimeters of mercury to kilopascals, multiply by 0.133.

Child-Pugh Classification of Severity of Liver Disease

Modified Child-Pugh classification of severity of liver disease according to the degree of ascites, the
plasma concentrations of bilirrubin and albumin, the prothrombin time, and the degree of encephalopathy.

Parameter Points assigned

1 2 3
Ascites Absent Slight Moderate
Bilirrubin, mg/dL </= 2 2-3 >3
Albumin, g/dL >3.5 2.8-3.5 <2.8
Prothrombin time
* Seconds over control 1-3 4-6 >6
* INR <1.8 1.8-2.3 >2.3
Encephalopathy None Grade 1-2 Grade 3-4

A total score of 5-6 is considered grade A (well-compensated disease); 7-9 is grade B (significant functional
compromise); and 10-15 is grade C (descompensated disease). These grades correlate with one- and two-
year patient survival.

Grade Points One-year patient survival Two-year patient survival

(%) (%)
A: well-compensated 5-6 100 85
disease
B: significant functional 7-9 80 60
compromise
C: descompensated 10-15 45 35
disease

Diagnostic Criteria for Idiopathic Hypereosinophilic Syndrome (HES)

Diagnostic Criteria for Idiopathic Hypereosinophilic Syndrome (HES) are:

1. Persistent eosinophilia of over 1500/cubic millimeter for longer than 6 month;
2. Lack of evidence of other known causes of secondary hypereosinophilia (SH);
3. Multiple organ involvement.

Diseases Associated with Eosinophilia

"Allergic" Diseases

Atopic and related diseases

Medication-related eosinophilias

Infectious Diseases

32
 Parasitic infections, mostly with helminths
Specific fungal infections: allergic bronchopulmonary aspergillosis, coccidioidomycosis (acute
and sometimes disseminated)
Other infections--infrequent, including HIV-1 and HTLV-1

Hematologic and Neoplastic Disorders

Hypereosinophilic syndrome
Leukemia
Lymphomas, including nodular sclerosing Hodgkin's disease
Tumor associated
Mastocytosis

Diseases with Specific Organ Involvement

Skin and subcutaneous diseases, including urticaria, bullous pemphigoid, eosinophilic cellulitis
(Well's syndrome), episodic angioedema with eosinophilia
Pulmonary diseases, including acute or chronic eosinophilic pneumonia, allergic
bronchopulmonary aspergillosis
Gastrointestinal diseases, including eosinophilic gastroenteritis
Neurologic diseases (e.g., eosinophilic meningitis)
Rheumatologic diseases, especially Churg-Strauss vasculitis; also eosinophilic fasciitis
Cardiac diseases (e.g., endomyocardial fibrosis)
Renal diseases, including drug-induced interstitial nephritis, eosinophilic cystitis, dialysis

Immunologic Reactions

Specific immune deficiency diseases: hyper-IgE syndrome, Omenn's syndrome

Transplant rejection: lung, kidney, liver

Endocrine

Hypoadrenalism: Addison's disease, adrenal hemorrhage

Other

Atheroembolic disease
Irritation of serosal surfaces, including peritoneal dialysis
Inherited

Diagnostic Criteria for Heparin-Induced Thrombocytopenia (HIT)

Heparin exposure >5 days

Relative thrombocytopenia: decrease in platelet count by 50% from baseline OR absolute
thrombocytopenia: decrease in platelet count to less than 100 to 150 x 109/L
Absence of other causes of thrombocytopenia
Development of new thrombosis, or extension of pre-existing thrombosis, while receiving heparin
therapy
Confirmation by laboratory testing
Return to normal platelet count when heparin is discontinued

33
Serology tests to determine HIT (listed in order of greatest to lowest sensitivity)

Serotonin release assay

Heparin/PF 4 ELISA
Platelet aggregation

Estimating the Pretest Probability of HIT: The "Four T's"

Points (0, 1, or 2 for Each of 4 Categories: Maximum Possible Score = 8)

2 1 0
Thrombocytopenia >50% Platelet fall to nadir 3050% Platelet fall, or <30% Platelet fall, or nadir
>/= 20 nadir 10-19 <10
Timing* of onset of Days 510, or </= day 1 >Day 10 or timing <Day 4 (no recent heparin)
platelet fall (or other with recent heparin (past unclear; or <day 1 with
sequelae of HIT) 30 days) recent heparin (past 31
100 days)
Thrombosis or other Proven new thrombosis; Progressive or recurrent None
sequelae skin necrosis; or acute thrombosis; erythematous
systemic reaction after skin lesions; suspected
intravenous UFH bolus thrombosis (not proven)
OTher cause(s) of None evident Possible Definite
platelet fall
UFH, Unfractionated heparin
Pretest probability score: 68 indicates high; 45, intermediate; and 03, low.
*First day of immunizing heparin exposure considered day 0.

Diagnostic Criteria for Systemic Mastocytosis (SM)

If at least 1 major and 1 one minor, or at least 3 minor criteria, are met, the diagnosis of Systemic
Mastocytosis (SM) can be established.

Major Criteria: Multifocal dense infiltrates of mast cells in bone marrow or other extracutaneous organ(s)
(>15 mast cells in aggregate)

Minor Criteria:

a) Mast cells in bone marrow or other extracutaneous organ(s) show an abnormal morphology (>
25%)
b) C-kit mutation at codon 816 in extracutaneous organ(s). (Activating mutations at codon 816; in
most cases, c-kit D816V)
c) Mast cells in bone marrow express CD2 and/or CD25
d) Serum total tryptase > 20 ng/mL (does not count in patients who have associated hematologic
clonal non-mast cell lineage disease-type disease)

WHO Classification of Mastocytosis

Variant Term (Abbreviation) Subvariants

Cutaneous Mastocytosis (CM) Urticaria Pigmentosa (UP) = Maculopapular CM (MPCM)

34

Indolent Systemic Mastocytosis
(ISM)
Systemic Mastocytosis with an
associated clonal hematologic non-
mast cell lineage disease (SM-
AHNMD)
Aggressive Systemic Mastocytosis
(ASM)
Mast Cell Leucemia (MCL)
Mast Cell Sarcoma (MCS)
Extracutaneous Mastocytoma
Diffuse CM (DCM)
Mastocytoma of Skin
Smouldering SM (SSM)
Isolated bone marrow mastocytosis (BMM)
Systemic Mastocytosis with Acute Myeloid Leukemia (SM-
AML)
Systemic Mastocytosis with Myelodysplastic Syndrome
(SM-MDS)
Systemic Mastocytosis with Myeloproliferative Disorder
(SM-MPD)
Systemic Mastocytosis with Chronic Myelomonocytic
Leukemia (SM-CMML)
Systemic Mastocytosis with Non-Hodgkins Lymphoma
(SM-NHL)
Systemic Mastocytosis with Hypereosinophilic Syndrome
(SM-HES)
Lymphadenopathic SM with eosinophilia (In a few cases, the
FIP1L1/PDGFRA-fusion gene may be detected)
Aleukemic MCL

WHO, World Health Organization

FAB Classification of Myelodysplastic Syndromes (MDS)

Refractory anemia (RA).

Cytopenia of at least one lineage in the peripheral blood (usually anemia)
Normal or hypercellular bone marrow with dysplastic changes
Less than 1 percent blasts in the peripheral blood and less than 5 percent blasts in the bone marrow
Refractory anemia with ringed sideroblasts (RARS)
Cytopenia (almost always anemia), dysplastic changes, and the same percentages of blood and
bone marrow blasts as in refractory anemia
Ringed sideroblasts accounting for more than 15 percent of all nucleated cells in the bone marrow
Refractory anemia with excess blasts (RAEB)
Cytopenia of two or more lineages in the peripheral blood
Dysplastic changes in all three lineages
Less than 5 percent blasts in the peripheral blood and between 5 and 20 percent blasts in the bone
marrow
Chronic myelomonocytic leukaemia (CML)
Peripheral-blood monocytosis (monocyte count, >110 9 per liter)
Less than 5 percent blasts in the peripheral blood and up to 20 percent blasts in the bone marrow
Refractory anemia with excess blasts in transformation (RAEB-T)
Hematologic features similar to those of refractory anemia with excess blasts
More than 5 percent blasts in the peripheral blood or between 21 and 30 percent blasts in the bone
marrow or the presence of Auer rods in the blasts

International Prognostic Scoring System for Myelodysplastic Syndromes

35
 Overall Score Median Survival
(yr)
Low (0) 5.7
Intermediate
1 (0.5 or 1.0) 3.5
2 (1.5 or 2.0) 1.2
High (>/=2.5) 0.4

The overall score is the sum of the scores for bone marrow blasts, karyotype, and cytopenias. The
percentage of blasts is scored as follows: <5 percent, 0; 5 to 10 percent, 0.5; 11 to 20 percent, 1.5; and 21 to
30 percent, 2.0. Cytogenetic features associated with a good prognosis (normal karyotype, Y-, 5q-, or 20q-)
are scored as 0; those associated with a poor prognosis (abnormal chromosome 7 or three or more
abnormalities) are scored as 1.0; and all other cytogenetic abnormalities, which are associated with an
intermediate prognosis, are scored as 0.5. A score of 0 is assigned if the patient has no cytopenia or only
one type, and a score of 0.5 is assigned if the patient has two or three types of cytopenia. The various types
of cytopenia are defined as follows: hemoglobin, <10 g per deciliter; absolute neutrophil count, <1500 per
cubic millimeter; and platelet count, <100,000 per cubic millimeter.

Diagnostic Criteria for Multiple Myeloma

Presence of an M-componenta in serum and/or urine plus clonal plasma cells in the bone marrow and/or a
documented clonal plasmacytoma

PLUS one or more of the following:b

Calcium elevation (>11.5 mg/dl) [>2.65 mmol/l]
Renal insufficiency (creatinine >2 mg/dl) [177 mmol/l or more]
Anemia (hemoglobin <10 g/dl or 2 g/dl <normal) (hemoglobin <12.5 mmol/lc or 1.25 mmol/l
<normal)
Bone disease (lytic lesions or osteopenia)

a
In patients with no detectable M-component, an abnormal serum FLC ratio on the serum FLC assay can
substitute and satisfy this criterion. For patients, with no serum or urine M-component and normal serum
FLC ratio, the baseline bone marrow must have >10% clonal plasma cells; these patients are referred to as
having non-secretory myeloma. Patients with biopsy-proven amyloidosis and/or systemic light chain
deposition disease (LCDD) should be classified as myeloma with documented amyloidosis or myeloma
with documented LCDD, respectively if they have >30% plasma cells and/or myeloma-related bone
disease.

b
Must be attributable to the underlying plasma cell disorder.

c
Note: Hemoglobin of 10 g/dl is 12.5 mmol/l [or 100 g/l].

Diagnostic Criteria for Polycythemia Vera (PV)

Criteria PVSG (Polycythemia Vera Study Group)

A1 Raised red cell mass (RCM), male > 36 ml/kg, female > 32 ml/kg
A2 Normal arterial oxygen saturation > 92%
A3 Splenomegaly

B1 Platelet count > 400 x 109/l

B2 White blood cell count (WBC) > 12 x 109/l
B3 Leucocyte alkaline phosphatase > 100
B4 Serum B12 > 900 pg/ml or unbound B12 binding capacity > 220 pg/ml

36
Diagnosis
A1 + A2 + A3 establishes PV
A1 + A2 + two of category B establishes PV

Criteria BCSH (British Committee for Standards in Haematology)

A1 Raised RCM or hematocrit (HCT) > 0.60 (males), > 0.56 (females)
A2 No secondary erythrocytosis
A3 Palpable spleen
A4 Abnormal karyotype

B1 Platelet count > 400 x 109/l

B2 Neutrophil count > 10 x 109/l
B3 Splenomegaly on ultrasound scanning
B4 Low serum EPO or characteristic burst forming units - erythroid (BFU-E) growth

Diagnosis
A1 + A2 + A3 or A4 establishes PV
A1 + A2 + two of B establishes PV

Criteria WHO (World Health Organization)

A1 Raised RCM or haemoglobin (Hb) > 18.5 (males), > 16.5 (females)
A2 No secondary erythrocytosis
A3 Splenomegaly
A4 Abnormal karyotype (other than Ph chromosome or BCR/ABL fusion gene in marrow cells)
A5 Endogenous erythroid colony (EEC) formation

B1 Platelet count > 400 x 109/l

B2 WBC > 12 x 109/l
B3 Bone marrow biopsy (BMB) showing panmyelosis with erythroid and megakaryocytic proliferation
B4 Low serum erythropoietin (EPO)

Diagnosis
A1 + A2 and any other category A establishes PV
A1 + A2 + two of category B establishes PV

Diagnostic Criteria of Hemorrhage in MRI of the Brain

Age T1 Weighted T2 Weighted

Hyperacute Hours old, mainly Hypointense Hyperintense
oxyhemoglobin with
surrounding edema
Acute Days old, mainly Hypointense Hypointense, surrounded
deoxyhemoglobin with by hyperintense margin
surrounding edema
Subacute Weeks old, mainly Hyperintense Hypointense, early
methemoglobin subacute with
predominantly intracellular
methemoglobin.
Hyperintense, late subacute

37
 with predominantly
extracellular
methemoglobin
Chronic Years old, hemosiderin slit Hypointense Hypointense slit, or
or hemosiderin margin hypointense margin
surrounding fluid cavity surrounding hyperintense
fluid cavity

Summary of Recommendations for Management of Hypertension in BHS-IV

Provide advice on life-style modifications for all people with high blood pressure (BP) and those with
borderline or high-normal BP.

Initiate antihypertensive drug therapy in people with sustained systolic BP (SBP) >/= 160 mmHg or
sustained diastolic BP (DBP) >/= 100 mmHg.

Make treatment decisions in people with sustained SBP between 140 and 159 mmHg and/or sustained
DBP between 90 and 99 mmHg according to the presence or absence of cardiovascular disease (CVD),
other target organ damage (TOD), or an estimated CVD risk of >/= 20% over 10 years, according to the
Joint British Societies CVD risk assessment programme or risk chart.

In people with diabetes mellitus, initiate antihypertensive drug therapy if SBP is sustained >/= 140 mmHg
and/or DBP is sustained >/= 90 mmHg.

In non-diabetic people with hypertension, optimal BP treatment goals are: SBP < 140 mmHg and DBP <
85 mmHg. The recommended minimum acceptable level of control (audit standard) is < 150/< 90 mmHg.

In hypertensive people with diabetes, chronic renal disease or established CVD, optimal BP goals are
lower: SBP < 130 mmHg and DBP < 80 mmHg. The audit standard is < 140/ < 80 mmHg.

Meta-analyses of BP-lowering trials suggest that, in general, the main determinant of benefit from BP-
lowering drugs is the achieved BP, rather than choice of therapy. In some circumstances, there are
compelling indications and contraindications for specific classes of antihypertensive drugs and these are
specified.

Most people with high BP will require at least two BP-lowering drugs to achieve the recommended BP
goals. A treatment algorithm (AB/CD) is provided to advise on the sequencing of drugs and logical drug
combinations. When there are no cost disadvantages, fixed drug combinations are recommended to reduce
the number of medications, which may enhance adherence to treatment (C).

Other drugs that reduce CVD risk must also be considered, notably: low-dose aspirin and statin therapy.
Vitamin supplements are not recommended.

Unless contraindicated, low-dose aspirin (75 mg/day) is recommended for the secondary prevention of
ischaemic CVD, and primary prevention in people over the age of 50 years who have a 10-year CVD risk
>/= 20% and in whom BP is controlled to the audit standard.

Statin therapy is recommended for all people with high BP complicated by CVD, irrespective of baseline
total cholesterol or low density lipoprotein (LDL)-cholesterol levels. Similarly, statin therapy is also
recommended for primary prevention in people with high BP who have a 10-year CVD risk >/= 20%.
Optimal cholesterol lowering should reduce total cholesterol by 25% or LDL-cholesterol by 30% or
achieve a total cholesterol of < 4.0 mmol/L or LDL-cholesterol of < 2.0 mmol/L, whichever is the greatest

38
reduction (A). A more conservative audit standard is suggested of < 5.0 mmol/L (190mg/dl) and < 3.0
mmol/L ( for total- and mg/dl) LDL-cholesterol respectively.

British Hypertension Society classification of blood pressure levels (BHS-IV)

Category Systolic blood Diastolic blood

pressure (mmHg) pressure (mmHg)
Optimal blood <120 <80
pressure
Normal blood <130 <85
pressure
High-normal blood 130-139 85-89
pressure
Grade 1 hypertension 140-159 90-99
(mild)
Grade 2 hypertension 160-179 100-109
(moderate)
Grade 3 hypertension >/= 180 >/= 110
(severe)
Isolated systolic 140-159 <90
hypertension (Grade
1)
Isolated systolic >/= 160 <90
hypertension (Grade
2)

This classification equates with that of the European Society of Hypertension (ESH) and that of World
Health Organization/ International Society of Hypertension (WHO/ISH), and is based on clinic blood
pressure values. If systolic blood pressure and diastolic blood pressure fall into different categories, the
higher value should be taken for classification.

1993 Revised Classification System for HIV Infection and Expanded AIDS Surveillance Case
Definition for Adolescents and Adults

Clinical Categories
CD4+ T Cell Categories A Asymptomatic, Acute B Symptomatic, Not A or C AIDS-Indicator
(Primary) HIV or PGL C Conditions Conditions
>500/uL A1 B1 C1
200499/uL A2 B2 C2
<200/uL A3 B3 C3

PGL, progressive generalized lymphadenopathy.

Clinical Categories of HIV Infection

39
Category A: Consists of one or more of the conditions listed below in an adolescent or adult (>13 years)
with documented HIV infection.
Conditions listed in categories B and C must not have occurred.
Asymptomatic HIV infection
Persistent generalized lymphadenopathy
Acute (primary) HIV infection with accompanying illness or history of acute HIV infection

Category B: Consists of symptomatic conditions in an HIV-infected adolescent or adult that are not
included among conditions listed in clinical category C and that meet at least one of the following criteria:
(1) The conditions are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or
(2) the conditions are considered by physicians to have a clinical course or to require management that is
complicated by HIV infection. Examples include, but are not limited to, the following:

Bacillary angiomatosis
Candidiasis, oropharyngeal(thrush)
Candidiasis, vulvovaginal; persistent, frequent, or poorly responsive to therapy
Cervical dysplasia (moderate or severe)/cervical carcinoma in situ
Constitutional symptoms, such as fever (38.5C) or diarrhea lasting >1 month
Hairy leukoplakia, oral
Herpes zoster (shingles), involving at least two distinct episodes or more than one dermatome
Idiopathic thrombocytopenic purpura
Listeriosis
Pelvic inflammatory disease, particularly if complicated by tuboovarian abscess
Peripheral neuropathy

Category C: Conditions listed in the AIDS surveillance case definition.

Candidiasis of bronchi, trachea, or lungs

Candidiasis, esophageal
Cervical cancer, invasive
Coccidioidomycosis, disseminated or extrapulmonary
Cryptococcosis, extrapulmonary
Cryptosporidiosis, chronic intestinal (>1 months duration)
Cytomegalovirus disease (other than liver, spleen, or nodes)
Cytomegalovirus retinitis (with loss of vision)
Encephalopathy, HIV-related
Herpes simplex: chronic ulcer(s) (>1 months duration); or bronchitis, pneumonia, or esophagitis
Histoplasmosis, disseminated or extrapulmonary
Isosporiasis, chronic intestinal (>1 months duration)
Kaposis sarcoma
Lymphoma, Burkitts (or equivalent term)
Lymphoma, primary, of brain
Mycobacterium avium complex or M. kansasii, disseminated or extrapulmonary
Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary)
Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
Pneumocystis carinii pneumonia
Pneumonia, recurrent
Progressive multifocal leukoencephalopathy
Salmonella septicemia, recurrent
Toxoplasmosis of brain
Wasting syndrome due to HIV

40
Definition of Acute Otitis Media (AOM)

A diagnosis of AOM requires:

1. a history of acute onset of signs and symptoms,

2. the presence of middle-ear effusion (MEE), and
3. signs and symptoms of middle-ear inflammation.

Elements of the definition of AOM are all of the following:

1. Recent, usually abrupt, onset of signs and symptoms of middle-ear inflammation and MEE
2. The presence of MEE that is indicated by any of the following:

a. Bulging of the tympanic membrane

b. Limited or absent mobility of the tympanic membrane
c. Air-fluid level behind the tympanic membrane
d. Otorrhea
3. Signs or symptoms of middle-ear inflammation as indicated by either

a. Distinct erythema of the tympanic membrane or

b. Distinct otalgia (discomfort clearly referable to the ear[s] that results in interference with or
precludes normal activity or sleep)

CURB-65 and CRB-65 Severity Scores for Community-Acquired Pneumonia (CAP)

Clinical factor Points

Confusion 1
Blood urea nitrogen > 19 mg per dL 1
Respiratory rate > 30 breaths per minute 1
Systolic blood pressure < 90 mm Hg 1
or
Diastolic blood pressure < 60 mm Hg
Age > 65 years 1
Total points:

CURB-65 score Mortality (%) Recommendation

0 0.6
1 2.7
2 6.8
3 14.0
4 or 5 27.8
Low risk; consider home treatment
Short inpatient hospitalization or closely supervised outpatient
treatment
Severe pneumonia; hospitalize and consider admitting to
intensive care

CRB-65 score Mortality (%) Recommendation

0 0.9 Very low risk of death; usually does not require hospitalization

41
 1 5.2 Increased risk of death; consider hospitalization
2 12.0
3 or 4 31.2 High risk of death; urgent hospitalization

CURB-65 = Confusion, Urea nitrogen, Respiratory rate, Blood pressure, 65 years of age and older.

CRB-65 = Confusion, Respiratory rate, Blood pressure, 65 years of age and older.

Classification of Fever of Unknown Origin (FUO)

Category of FUO Definition Common etiologies

Classic Temperature >38.3C (100.9F)
Duration of >3 weeks
Evaluation of at least 3 outpatient visits
or 3 days in hospital
Nosocomial Temperature >38.3C
Patient hospitalized >=24 hours but no
fever or incubating on admission
Evaluation of at least 3 days
Immune deficient Temperature >38.3C
(neutropenic) Neutrophil count <=500 per mm3
Evaluation of at least 3 days
HIV-associated Temperature >38.3C
Duration of >4 weeks for outpatients,
>3 days for inpatients
HIV infection confirmed
Infection, malignancy, collagen vascular
disease
Clostridium difficile enterocolitis, drug-
induced, pulmonary embolism, septic
thrombophlebitis, sinusitis
Opportunistic bacterial infections,
aspergillosis, candidiasis, herpes virus
Cytomegalovirus, Mycobacterium avium-
intracellulare complex, Pneumocystis
carinii pneumonia, drug-induced, Kaposi's
sarcoma, lymphoma

HIV = human immunodeficiency virus.

Common Etiologies of Fever of Unknown Origin

Infections

Tuberculosis (especially extrapulmonary)

Abdominal abscesses
Pelvic abscesses
Dental abscesses
Endocarditis
Osteomyelitis
Sinusitis
Cytomegalovirus
Epstein-Barr virus
Human immunodeficiency virus
Lyme disease
Prostatitis
Sinusitis

Malignancies

42
 Chronic leukaemia
Lymphoma
Metastatic cancers
Renal cell carcinoma
Colon carcinoma
Hepatoma
Myelodysplastic syndromes
Pancreatic carcinoma
Sarcomas

Autoimmune conditions

Adult Still's disease

Polymyalgia rheumatica
Temporal arteritis
Rheumatoid arthritis
Rheumatoid fever
Inflammatory bowel disease
Reiter's syndrome
Systemic lupus erythematosus
Vasculitides

Miscellaneous

Drug-induced fever
Complications from cirrhosis
Factitious fever
Hepatitis (alcoholic, granulomatous, or lupoid)
Deep venous thrombosis
Sarcoidosis

MASCC Index Score for Identifying Low-Risk Febrile Neutropenic Cancer Patients

Scoring system for risk of complications among febrile neutropenic patients, based on the Multinational
Association for Supportive Care in Cancer (MASCC) predictive model.

Characteristic Point score

Burden of illness
*No or mild symptoms 5
*Moderate symptoms 3
No hypotension 5
No chronic obstructive pulmonary disease 4
Solid tumor or no previous fungal infection in 4
hematologic tumor
Outpatient status 3
No dehydration 3
Aged <60 years 2

The maximum value in this system is 26, and a score of <21 predicts a <5% risk for severe complications
and a very low mortality (<1%) in febrile neutropenic patients.

43
CDC Diagnostic Criteria for Psittacosis (Ornithosis)

1996 Case Definition

Clinical description

An illness characterized by fever, chills, headache, photophobia, cough, and myalgia

Laboratory criteria for diagnosis

Isolation of Chlamydia psittaci from respiratory secretions, or

Fourfold or greater increase in antibody against C. psittaci by complement fixation (CF) or
microimmunofluorescence (MIF) to a reciprocal titer of greater than or equal to 32 between paired
acute- and convalescent-phase serum specimens, or
Presence of immunoglobulin M antibody against C. psittaci by MIF to a reciprocal titer of greater
than or equal to 16

Case classification

Probable: a clinically compatible case that is epidemiologically linked to a confirmed case or that
has supportive serology (e.g., C. psittaci titer of greater than or equal to 32 in one or more serum
specimens obtained after onset of symptoms)
Confirmed: a clinically compatible case that is laboratory confirmed

Comment

The serologic findings by CF also may occur as a result of infection with Chlamydia pneumoniae or
Chlamydia trachomatis. The MIF might be more specific for infection with C. psittaci, but experience with
and availability of this newer test are more limited.

Case Definition of Streptococcal Toxic-Shock Syndrome (Streptococcal TSS) and Necrotizing

Fasciitis*

I. Streptococcal TSS
A. Isolation of group A Streptococcus
1. From a sterile site
2. From a nonsterile body site
B. Clinical signs of severity
1. Hypotension
2. Clinical and laboratory abnormalities (requires two or more of the following):
a) Renal impairment
b) Coagulopathy
c) Liver abnormalities
d) Acute respiratory distress syndrome
e) Extensive tissue necrosis, i.e., necrotizing fasciitis
f) Erythematous rash

Definite Case = A1 + B (1+2)

Probable Case = A2 + B (1+2)

II. Necrotizing fasciitis

A. Definite case
1. Necrosis of soft tissues with involvement of the fascia

44
 PLUS
2. Serious systemic disease, including one or more of the following:
a) Death
b) Shock (systolic blood pressure <90 mmHg).
c) Disseminated intravascular coagulopathy
d) Failure of organ systems
a. respiratory failure
b. liver failure
c. renal failure
3. Isolation of group A Streptococcus from a normally sterile body site
B. Suspected case
1. 1+2 and serologic confirmation of group A streptococcal infection by a 4-fold rise against:
a) streptolysin O
b) DNase B
2. 1+2 and histologic confirmation:
Gram-positive cocci in a necrotic soft tissue infection

*Streptococcal toxic-shock syndrome (streptococcal TSS) is defined as any group A streptococcal infection
associated with the early onset of shock and organ failure.

1996 CDC Case Definition for Syphilis (Treponema pallidum)

Syphilis is a complex sexually transmitted disease that has a highly variable clinical course. Classification
by a clinician with expertise in syphilis may take precedence over the following case definitions developed
for surveillance purposes.

Syphilis, primary

Clinical description: A stage of infection with Treponema pallidum characterized by one or more chancres
(ulcers); chancres might differ considerably in clinical appearance.

Laboratory criteria for diagnosis: Demonstration of T. pallidum in clinical specimens by darkfield

microscopy, direct fluorescent antibody (DFA-TP), or equivalent methods.

Case classification:

Probable: a clinically compatible case with one or more ulcers (chancres) consistent with primary
syphilis and a reactive serologic test (nontreponemal: Venereal Disease Research Laboratory
[VDRL] or rapid plasma reagin [RPR]; treponemal: fluorescent treponemal antibody absorbed
[FTA-ABS] or microhemagglutination assay for antibody to T. pallidum [MHA-TP])
Confirmed: a clinically compatible case that is laboratory confirmed

Syphilis, secondary

Clinical description: A stage of infection caused by T. pallidum and characterized by localized or diffuse
mucocutaneous lesions, often with generalized lymphadenopathy. The primary chancre may still be present.

Laboratory criteria for diagnosis: Demonstration of T. pallidum in clinical specimens by darkfield

microscopy, DFA-TP, or equivalent methods

45
Case classification:

Probable: a clinically compatible case with a nontreponemal (VDRL or RPR) titer greater than or
equal to 4
Confirmed: a clinically compatible case that is laboratory confirmed

Syphilis, latent

Clinical description: A stage of infection caused by T. pallidum in which organisms persist in the body of
the infected person without causing symptoms or signs. Latent syphilis is subdivided into early, late, and
unknown categories based on the duration of infection.

Case classification:

Probable: no clinical signs or symptoms of syphilis and the presence of one of the following:

No past diagnosis of syphilis, a reactive nontreponemal test (i.e., VDRL or RPR), and a reactive
treponemal test (i.e., FTA-ABS or MHA-TP)
A past history of syphilis therapy and a current nontreponemal test titer demonstrating fourfold or
greater increase from the last nontreponemal test titer

Syphilis, early latent

Clinical description: A subcategory of latent syphilis. When initial infection has occurred within the
previous 12 months, latent syphilis is classified as early latent.

Case classification:

Probable: latent syphilis in a person who has evidence of having acquired the infection within the previous
12 months based on one or more of the following criteria:

Documented seroconversion or fourfold or greater increase in titer of a nontreponemal test during

the previous 12 months
A history of symptoms consistent with primary or secondary syphilis during the previous 12
months
A history of sexual exposure to a partner who had confirmed or probable primary or secondary
syphilis or probable early latent syphilis (documented independently as duration less than 1 year)
Reactive nontreponemal and treponemal tests from a person whose only possible exposure
occurred within the preceding 12 months

Syphilis, late latent

Clinical description: A subcategory of latent syphilis. When initial infection has occurred greater than 1
year previously, latent syphilis is classified as late latent.

Case classification:

46
Probable: latent syphilis (see Syphilis, latent) in a patient who has no evidence of having acquired the
disease within the preceding 12 months (see Syphilis, early latent) and whose age and titer do not meet the
criteria specified for latent syphilis of unknown duration.

Syphilis, latent, of unknown duration

Clinical description: A subcategory of latent syphilis. When the date of initial infection cannot be
established as having occurred within the previous year and the patient's age and titer meet criteria
described below, latent syphilis is classified as latent syphilis of unknown duration.

Case classification:

Probable: latent syphilis (see Syphilis, latent) that does not meet the criteria for early latent
syphilis, and the patient is aged 13-35 years and has a nontreponemal titer greater than or equal to
32

Neurosyphilis

Clinical description: Evidence of central nervous system infection with T. pallidum

Laboratory criteria for diagnosis: A reactive serologic test for syphilis and reactive VDRL in
cerebrospinal fluid (CSF)

Case classification:

Probable: syphilis of any stage, a negative VDRL in CSF, and both the following:

Elevated CSF protein or leukocyte count in the absence of other known causes of these
abnormalities
Clinical symptoms or signs consistent with neurosyphilis without other known causes for these
clinical abnormalities

Confirmed: syphilis of any stage that meets the laboratory criteria for neurosyphilis

Syphilis, late, with clinical manifestations other than neurosyphilis (late benign syphilis and
cardiovascular syphilis)

Clinical description: Clinical manifestations of late syphilis other than neurosyphilis may include
inflammatory lesions of the cardiovascular system, skin, and bone. Rarely, other structures (e.g., the upper
and lower respiratory tracts, mouth, eye, abdominal organs, reproductive organs, lymph nodes, and skeletal
muscle) may be involved. Late syphilis usually becomes clinically manifest only after a period of 15-30
years of untreated infection.

Laboratory criteria for diagnosis: Demonstration of T. pallidum in late lesions by fluorescent antibody or
special stains (although organisms are rarely visualized in late lesions)

47
Case classification:

Probable: characteristic abnormalities or lesions of the cardiovascular system, skin, bone, or other
structures with a reactive treponemal test, in the absence of other known causes of these
abnormalities, and without CSF abnormalities and clinical symptoms or signs consistent with
neurosyphilis
Confirmed: a clinically compatible case that is laboratory confirmed

Comment: Analysis of CSF for evidence of neurosyphilis is necessary in the evaluation of late syphilis
with clinical manifestations.

Syphilitic Stillbirth

Clinical case definition: A fetal death that occurs after a 20-week gestation or in which the fetus weighs
greater than 500 g and the mother had untreated or inadequately treated* syphilis at delivery

Comment: For reporting purposes, syphilitic stillbirths should be reported as cases of congenital syphilis.

*Inadequate treatment consists of any non-penicillin therapy or penicillin given less than 30 days before
delivery.

Case Definition of Staphylococcal Toxic Shock Syndrome (TSS)

An illness with the following clinical manifestations:

1. Fever: temperature > 38.9 C (102 F)
2. Rash: diffuse macular erythroderma
3. Desquamation: 1-2 weeks after onset of illness, particularly palms and soles
4. Hypotension: systolic blood pressure < 90 mm Hg for adults or less than fifth percentile by age for
children <16 years of age; orthostatic drop in diastolic blood pressure greater than or equal to 15
mm Hg from lying to sitting, orthostatic syncope, or orthostatic dizziness

Multisystem involvement: three or more of the following:

1. Gastrointestinal: vomiting or diarrhea at onset of illness
2. Muscular: severe myalgia or creatine phosphokinase level at least twice the upper limit of normal
for laboratory
3. Mucous membrane: vaginal, oropharyngeal, or conjunctival hyperemia
4. Renal: blood urea nitrogen or creatinine at least twice the upper limit of normal for laboratory or
urinary sediment with pyuria (greater than or equal to 5 leukocytes per high-power field) in the
absence of urinary tract infection
5. Hepatic: total bilirubin, serum glutamic-oxaloacetic transaminase (AST, SGOT), or serum
glutamic-pyruvic transaminase (ALT, SGPT) at least twice the upper limit of normal for laboratory
6. Hematologic: platelets <100,000/mm3
7. Central nervous system: disorientation or alterations in consciousness without focal neurologic
signs when fever and hypotension are absent

Negative results on the following tests, if obtained:

1. Blood, throat, or cerebrospinal fluid cultures (blood culture may be positive for Staphylococcus
aureus)
2. Rise in titer to Rocky Mountain spotted fever, leptospirosis, or measles

Case classification
Probable: a case with five of the six clinical findings described above

48
 Confirmed: a case with all six of the clinical findings described above, including desquamation,
unless the patient dies before desquamation could occur

Diagnostic Criteria for Tuberculosis Disease

Definite diagnosis

Clinical picture consistent with tuberculosis; bacteriologic confirmation (culture, gene probe/NAA
+ AFB smear); histologic findings

Probable diagnosis

Clinical picture consistent with tuberculosis; exclusion of other diagnostic considerations;

presence of highly specific tuberculosis (surrogate) marker

Likely diagnosis

Clinical picture consistent with tuberculosis; exclusion of other diagnostic considerations; typical
response to antituberculosis treatment (in absence of other treatment)

NOTE. AFB, acid-fast bacilli; NAA, nucleic acid amplification.

Diagnosis of Visceral Leishmaniasis (Kala-Azar)

Leishmania donovani and Leishmania infantum/Leishmania chagasi are responsible for most of the cases of
visceral leishmaniasis

In an endemic area, the constellation of prolonged fever, progressive weight loss, weakness, pronounced
splenomegaly, hepatomegaly, anemia, leukopenia, and hypergammaglobulinemia is highly suggestive of
visceral leishmaniasis. The diagnosis is more difficult in persons in whom fever or splenomegaly are
absent; in travelers who develop symptoms after leaving endemic areas; and in those with concurrent AIDS
who present with atypical manifestations.

The diagnosis can be confirmed by demonstrating amastigotes in tissue or isolating promastigotes in

culture. Splenic aspiration for Wright-Giemsa stained smears and for culture is the most sensitive method
for parasite identification.

Bone marrow aspiration is safer, but less sensitive. Amastigotes are seen in approximately two thirds of
patients. Liver biopsy is less likely to yield the diagnosis than is splenic puncture or bone marrow biopsy
and carries the risk of hemorrhage. Lymph node aspiration or biopsy may be diagnostic when enlarged
nodes are present.

Antileishmanial antibodies are typically present in high titer in immunocompetent patients with visceral
leishmaniasis. Enzyme-linked immunosorbent assay (ELISA) and dipstick tests using L. infantum/L.
chagasi recombinant k39, a kinesin-like antigen, have good sensitivity and specificity for the diagnosis of
visceral leishmaniasis in immunocompetent persons.

The leishmanin (Montenegro) skin test is negative in patients with active visceral leishmaniasis. It becomes
positive in the majority of those in whom infection spontaneously resolves and in patients who have
undergone successful chemotherapy.

ICHD-II Diagnostic Criteria for Headache Attributed to Non-Vascular Intracranial Disorder

49
Headache attributed to idiopathic intracranial hypertension (IIH)

A. Progressive headache with at least 1 of the following characteristics and fulfilling criteria C-D:

1. Daily occurrence
2. Diffuse and/or constant (non-pulsating) pain
3. Aggravated by coughing or straining

B. Intracranial hypertension fulfilling the following criteria:

1. Alert patient with neurological examination that either is normal or demonstrates any of the
following abnormalities:

a) Papilloedema
b) Enlarged blind spot
c) Visual field defect (progressive if untreated)
d) Sixth nerve palsy
2. Increased CSF pressure (>200 mm H2O in the nonobese, >250 mm H2O in the obese) measured
by lumbar puncture in the recumbent position or by epidural or intraventricular pressure
monitoring
3. Normal CSF chemistry (low CSF protein is acceptable) and cellularity
4. Intracranial diseases (including venous sinus thrombosis) ruled out by appropriate investigations
5. No metabolic, toxic or hormonal cause of intracranial hypertension

C. Headache develops in close temporal relation to increased intracranial pressure

D. Headache improves after withdrawal of CSF to reduce pressure to 120-170 mm H2O and resolves
within 72 hours of persistent normalisation of intracranial pressure

Headache attributed to increased intracranial pressure or hydrocephalus caused by neoplasm

A. Diffuse non-pulsating headache with at least 1 of the following characteristics and fulfilling criteria C-
D:

1. Associated with nausea and/or vomiting

2. Worsened by physical activity and/or manoeuvres known to increase intracranial pressure (such as
Valsalva manoeuvre, coughing or sneezing)
3. Occurring in attack-like episodes

B. Space-occupying intracranial tumour* demonstrated by CT or MRI and causing hydrocephalus

C. Headache develops and/or deteriorates in close temporal relation to the hydrocephalus

D. Headache improves within 7 days after surgical removal or volume-reduction of tumour

*including colloid cyst of the IIIrd ventricle.

Headache attributed directly to neoplasm

50
A. Headache with at least 1 of the following characteristics and fulfilling criteria C-D:

1. progressive
2. localised
3. orse in the morning
4. aggravated by coughing or bending forward

B. Intracranial neoplasm shown by imaging

C. Headache develops in temporal (and usually spatial) relation to the neoplasm

D. Headache resolves within 7 days after surgical removal or volume-reduction of neoplasm or treatment
with corticosteroids

CSD Revised Classification of Adult Insomnia

Primary Insomnia

Idiopathic insomnia: Insomnia arising in infancy or childhood with a persistent, unremitting

course
Psychophysiologic insomnia: Insomnia due to a maladaptive conditioned response in which the
patient learns to associate the bed environment with heightened arousal rather than sleep; onset
often associated with an event causing acute insomnia, with the sleep disturbance persisting
despite resolution of the precipitating factor
Paradoxical insomnia (sleep-state misperception): Insomnia characterized by a marked mismatch
between the patients description of sleep duration and objective polysomnographic findings

Secondary Insomnia

Adjustment insomnia: Insomnia associated with active psychosocial stressors

Inadequate sleep hygiene: Insomnia associated with lifestyle habits that impair sleep
Insomnia due to a psychiatric disorder: Insomnia due to an active psychiatric disorder, such as
anxiety or depression
Insomnia due to a medical condition: Insomnia due to a condition such as the restless legs
syndrome, chronic pain, nocturnal cough or dyspnea, or hot flashes
Insomnia due to a drug or substance: Insomnia due to consumption or discontinuation of
medication, drugs of abuse, alcohol, or caffeine

ICHD-II Diagnostic Criteria for Migraine

Migraine without aura

A. At least 5 attacks fulfilling criteria B-D

B. Headache attacks lasting 4-72 hours (untreated or unsuccessfully treated)

C. Headache has at least 2 of the following characteristics:

1. Unilateral location
2. Pulsating quality
3. Moderate or severe pain intensity
4. Aggravation by or causing avoidance of routine physical activity (eg, walking or climbing stairs)

51
D. During headache at least 1 of the following:

1. Nausea and/or vomiting

2. Photophobia and phonophobia

E. Not attributed to another disorder

Migraine with aura

A. At least 2 attacks fulfilling criterion B

B. Migraine aura fulfilling criteria B-C for one of the subforms (typical aura with migraine headache,
typical aura with non-migraine headache, typical aura without headache, familial hemiplegic migraine,
sporadic hemiplegic migraine, or basilar-type migraine)

C. Not attributed to another disorder

Typical aura with migraine headache

A. At least 2 attacks fulfilling criteria B-D

B. Aura consisting of at least 1 of the following, but no motor weakness:

1. Fully reversible visual symptoms including positive features (eg, flickering lights, spots or lines)
and/or negative features (ie, loss of vision)
2. Fully reversible sensory symptoms including positive features (ie, pins and needles) and/or
negative features (ie, numbness)
3. Fully reversible dysphasic speech disturbance

C. At least two of the following:

1. Homonymous visual symptoms and/or unilateral sensory symptoms

2. At least one aura symptom develops gradually over >/=5 minutes and/or different aura symptoms
occur in succession over >/=5 minutes
3. Each symptom lasts >/=5 and </=60 minutes

D. Headache fulfilling criteria B-D for Migraine without aura begins during the aura or follows aura
within 60 minutes

E. Not attributed to another disorder

Typical aura without headache

As Typical aura with migraine headache except:

52
B. Aura consisting of at least 1 of the following, with or without speech disturbance but no motor
weakness:

1. Fully reversible visual symptoms including positive features (eg, flickering lights, spots or lines)
and/or negative features (ie, loss of vision)
2. Fully reversible sensory symptoms including positive features (ie, pins and needles) and/or
negative features (ie, numbness)

D. Headache does not occur during aura nor follow aura within 60 minutes

Criteria for Evaluating the Effectiveness of Screening for a Risk Factor

Characteristics of the disease

1. Disease has serious consequences
2. Screening population has a high incidence* of disease
3. Risk factor is a good predictor of disease
Characteristics of the test
4. Screening test has a high accuracy for detecting the risk factor
5. Screening test detects the risk factor before the critical point
6. Screening test causes little morbidity
7. Screening test is affordable and available
Characteristics of prevention
8. Prevention exists
9. Prevention is more effective than treatment for the disease
10. Prevention is not too risky or toxic

* Incidence is the rate of new occurence of disease in a previously disease-free population over a particular
time period.

Criteria for the Metabolic Syndrome

ATP III Definition

Any three or more of the following criteria:

1. Waist circumference >102 cm (>40 in) in men and >88 cm (>35 in) in women
2. Serum triglycerides >/=150 mg/dL (>/=1.7 mmol/L)
3. Blood pressure >/=130/85 mm Hg
4. HDL-Cholesterol <40 mg/dL (<1.0 mmol/L) in men and <50 mg/dL (<1.3 mmol/L) in women
5. Fasting glucose 110 to 126 mg/dL (6.1 to 7.0 mmol/L) (100 mg/dL [>/=5.6 mmol/L] may be
applicable)
WHO Definition

Diabetes, IFP, IGT or insulin resistance (assessed by clamp studies) and at least two of the following
criteria:
1. Waist-to-hip ratio >0.90 in men or >0.85 in women.
2. Serum triglycerides 150 mg/dL (>/=1.7 mmol/l) or HDL cholesterol <36 mg/dL (<0.9 mmol/l) in
men and <40 mg/dL (<1.0 mmol/l) in women.
3. Blood pressure >/= 140/90 mmHg
4. Urinary albumin excretion rate >20 mcg/min or albumin to creatinine ratio >/= 30 mg/g

IFG; Impaired Fasting Glucose

IGT; Impaired Glucose Tolerance

53
The new International Diabetes Federation (IDF) definition

According to the new IDF definition, for a person to be defined as having the metabolic syndrome they
must have:

Central obesity (defined as waist circumference >/= 94cm for Europid men and >/= 80cm for
Europid women, with ethnicity specific values for other groups)

Plus any two of the following four factors:

1. Raised triglycerides (TG) level: >/= 150 mg/dL (1.7 mmol/L), or specific treatment for this lipid
abnormality
2. Reduced HDL cholesterol: < 40 mg/dL (1.03 mmol/L) in males and < 50 mg/dL (1.29 mmol/L) in
females, or specific treatment for this lipid abnormality
3. Raised blood pressure: systolic BP >/= 130 or diastolic BP >/= 85 mm Hg, or treatment of
previously diagnosed hypertension
4. Raised fasting plasma glucose (FPG) >/= 100 mg/dL (5.6 mmol/L), or previously diagnosed type
2 diabetes. If above 5.6 mmol/L or 100 mg/dL, oral glucose tolerance test (OGTT) is strongly
recommended but is not necessary to define presence of the syndrome.

Indications for Percutaneous Renal Biopsy

Indications for percutaneous needle biopsy include

1. Unexplained acute renal failure or chronic renal insufficiency;
2. Acute nephritic syndromes;
3. Unexplained proteinuria and hematuria;
4. Previously identified and treated lesions to plan future therapy;
5. Systemic diseases associated with kidney dysfunction, such as systemic lupus erythematosus
(SLE), Goodpasture's syndrome, and Wegener's granulomatosis, to confirm the extent of renal
involvement and to guide management;
6. Suspected transplant rejection, to differentiate it from other causes of acute renal failure; and
7. To guide treatment.

Relative contraindications include a solitary or ectopic kidney (exception: transplant allografts), horseshoe
kidney, uncorrected bleeding disorder, severe uncontrolled hypertension, renal infection, renal neoplasm,
hydronephrosis, end-stage renal disease (ESRD), congenital anomalies, multiple cysts, or uncooperative
patient.

Definition and Stages of Chronic Kidney Disease (CKD)

NKF Definition of Chronic Kidney Disease

Kidney damage for three or more months, as defined by structural or functional abnormalities of
the kidney, with or without decreased GFR, manifested by pathologic abnormalities or markers of
kidney damage, including abnormalities in the composition of the blood or urine or abnormalities
in imaging tests
GFR < 60 mL per minute per 1.73 m2 for three months or more, with or without kidney damage

NKF Classification of Chronic Kidney Disease

54
Stage Description GFR (mL per minute per Action plan
1.73 m2)
- At increased risk for > 60 (with risk factors for Screening, reduction of risk factors for chronic
chronic kidney chronic kidney disease) kidney disease
disease
1 Kidney damage with > 90 Diagnosis and treatment, treatment of comorbid
normal or elevated conditions, interventions to slow disease
GFR progression, reduction of risk factors for
cardiovascular disease
2 Kidney damage with 60 to 89 Estimation of disease progression
mildly decreased
GFR
3 Moderately 30 to 59 Evaluation and treatment of disease complications
decreased GFR
4 Severely decreased 15 to 29 Preparation for kidney replacement therapy
GFR (dialysis, transplantation)
5 Kidney failure < 15 (or dialysis) Kidney replacement therapy if uremia is present

Risk Factors for Chronic Kidney Disease and Its Outcomes

Type Definition Examples

Susceptibility Factors that increase susceptibility Older age, family history of chronic kidney disease,
factors to kidney damage reduction in kidney mass, low birth weight, U.S. racial
or ethnic minority status, low income or educational
level
Initiation Factors that directly initiate kidney Diabetes mellitus, high blood pressure, autoimmune
factors damage diseases, systemic infections, urinary tract infections,
urinary stones, obstruction of lower urinary tract, drug
toxicity
Progression Factors that cause worsening kidney Higher level of proteinuria, higher blood pressure
factors damage and faster decline in kidney level, poor glycemic control in diabetes, smoking
function after kidney damage has
started
End-stage Factors that increase morbidity and Lower dialysis dose (Kt/V)*, temporary vascular
factors mortality in kidney failure access, anemia, low serum albumin level, late referral
for dialysis

*-In Kt/V (accepted nomenclature for dialysis dose), "K" represents urea clearance, "t" represents time, and
"V" represents volume of distribution for urea.

NKF = National Kidney Foundation; GFR = glomerular filtration rate.

RIFLE Criteria for Acute Renal Dysfunction

Category GFR Criteria Urine Output (UO)

Criteria
Risk Increased creatinine x1.5 or UO < 0.5ml/kg/h x 6 hr High
GFR decrease > 25% Sensitivity
Injury Increased creatinine x2 or UO < 0.5ml/kg/h x 12 hr
GFR decrease > 50%

55
Failure Increase creatinine x3 or UO < 0.3ml/kg/h x 24 hr or
GFR decrease > 75% Anuria x 12 hrs

Loss Persistent ARF = complete loss of kidney function > 4

weeks
ESKD End Stage Kidney Disease (> 3 months)
GFR; Glomerular Filtration Rate
ARF; Acute Renal Failure
ESKD; End Stage Kidney Disease

ABCD2 Score for Transient Ischemic Attack (TIA)

A simple score (ABCD2) to identify individuals at high early risk of stroke after transient ischemic attack.

A (Age); 1 point for age >60 years,

B (Blood pressure > 140/90 mmHg); 1 point for hypertension at the acute evaluation,

C (Clinical features); 2 points for unilateral weakness, 1 for speech disturbance without weakness,
and

D (symptom Duration); 1 point for 1059 minutes, 2 points for >60 minutes.

D (Diabetes); 1 point
Total scores ranged from 0 (lowest risk) to 7 (highest risk).

Stroke risk at 2 days, 7 days, and 90 days:

Scores 0-3: low risk
Scores 4-5: moderate risk
Scores 6-7: high risk

Sensory Dermatome Maps

The word dermatome refers to a correspondence between the skin and the nervous system. Sensory
dermatome maps used to help localize the level of neurologic deficit.

56
Levels of principal dermatomes

C5 Clavicles
C5, 6, 7 Lateral parts of upper limbs
C8, Th1 Medial sides of upper limbs
C6 Thumb

57
C6, 7, 8 Hand
C8 Ring and little fingers
Th4 Level of nipples
Th10 Level of umbilicus
Th12 Inguinal or groin regions
L1, 2, 3, 4 Anterior and inner surfaces of lower limbs
L4, 5, S1 Foot
L4 Medial side of great toe
S1, 2, L5 Posterior and outer surfaces of lower limbs
S1 Lateral margin of foot and little toe
S2, 3, 4 Perineum

Related Criteria

Clinical Criteria for Do-Not-Resuscitate (DNR) Orders in Acute Stroke

A DNR order may be written any time that two of the following clinical criteria are present and the
prognosis has become clear for and shared whenever possible between physician(s), patient, and family (or
appropriate surrogate).

1. Severe Stroke
Clinically severe stroke produces persisting (more than 24 hours) and sometimes deteriorating neurological
deficit, often with early impairment of consciousness leading to total dependency of the patient in activities
of daily living. The patient must have little or no active movement on at least one side of the body, with
either impaired consciousness, global aphasia, or lack of response indicating cognition (Glasgow Coma
Scale score of less than 9, Canadian Neurological Scale score of less than 5.0).

2. Life-Threatening Brain Damage

Life-threatening brain damage is associated with brain stem compression caused by large intracerebral
hemorrhage (ICH), usually with intraventricular extension; large hemispheric infarction with midline shift;
infratentorial strokes involving multiple levels in the brain stem; or cerebellar lesions.*

3. Significant Comorbidities
The following nonneurological conditions are important risk factors for death within the first month after
stroke: pneumonia, pulmonary embolism, sepsis, recent myocardial infarction, cardiomyopathy, and life-
threatening arrhythmias. These comorbid factors should be considered part of expected consequences of
severe stroke pointing to an increased likelihood of death in the subacute phase of stroke.

*Fatal outcome of ICH is associated with a volume of > 60 mL on CT scans. Currently available data lack
precision in quantifying imaging criteria and size of life-threatening hemispheric infarctions and
infratentorial lesions.

FOUR Score for Comatose Patients

Eye response
4 = eyelids open or opened, tracking, or blinking to command
3 = eyelids open but not tracking

58
2 = eyelids closed but open to loud voice
1 = eyelids closed but open to pain
0 = eyelids remain closed with pain

Motor response
4 = thumbs-up, fist, or peace sign
3 = localizing to pain
2 = flexion response to pain
1 = extension response to pain
0 = no response to pain or generalized myoclonus status

Brainstem reflexes
4 = pupil and corneal reflexes present
3 = one pupil wide and fixed
2 = pupil or corneal reflexes absent
1 = pupil and corneal reflexes absent
0 = absent pupil, corneal, and cough reflex

Respiration
4 = not intubated, regular breathing pattern
3 = not intubated, CheyneStokes breathing pattern
2 = not intubated, irregular breathing
1 = breathes above ventilator rate
0 = breathes at ventilator rate or apnea

FOUR = Full Outline of UnResponsiveness.

JNC-VII Classification and management of blood pressure for adults

BP SBP* DBP* Lifestyle Initial drug therapy

Classification mmHg mmHg Modification Without Compelling With Compelling
Indication Indications
Normal <120 and <80 Encourage No antihypertensive drug Drug(s) for compelling
Prehypertension 120-139 or 80-89 Yes indicated. indications.
Stage 1 140-159 or 90-99 Yes Thiazide-type diuretics Drug(s) for the compelling
Hypertension for most. May consider indications.
ACEI, ARB, BB, CCB, Other antihypertensive
or combination. drugs (diuretics, ACEI,
Stage 2 >/=160 or >/=100 Yes Two-drug combination ARB, BB, CCB) as
Hypertension for most (usually needed.
thiazide-type diuretic and
ACEI or ARB or BB or
CCB).

DBP, diastolic blood pressure; SBP, systolic blood pressure.

Drug abbreviations: ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker;
BB, beta-blocker; CCB, calcium channel blocker.

Diagnostic Criteria for Kawasaki Disease

Presence of at least five of six conditions:

59
 1. Fever for five days or more
2. Bilateral conjunctival injection without exudate
3. Polymorphous exanthem
4. Changes in lips and mouth:
Reddened, dry, or cracked lips
Strawberry tongue
Diffuse redness of oral or pharyngeal mucosa
5. Changes in extremities:
Reddening of palms or soles
Indurative oedema of hands or feet
Desquamation of skin of hands, feet, and groin (in convalescence)
6. Cervical lymphadenopathy:
More than 15 mm in diameter, usually unilateral, single, non-purulent, and painful

Exclusion of diseases with similar presentation:

Staphylococcal infection (such as scalded skin syndrome, toxic shock syndrome)
Streptococcal infection (such as scarlet fever, toxic shock-like syndrome). Throat carriage of group
A streptococcus does not exclude the possibility of Kawasaki disease
Measles and other viral exanthems
Leptospirosis
Rickettsial disease
Stevens-Johnson syndrome
Drug reaction
Juvenile rheumatoid arthritis

Elevated erythrocyte sedimentation rate (ESR), anemia, and thrombocytosis are associated with Kawasaki
disease and can support the diagnosis. Coronary artery aneurysms, the most serious consequence of
Kawasaki disease, are seen in 20% of untreated patients, and long-term consequences include early
atherosclerosis, coronary stenosis, and myocardial infarction.

ICHD-II Diagnostic Criteria for Cluster Headache

Cluster headache

A. At least 5 attacks fulfilling criteria B-D

B. Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 minutes if
untreated

C. Headache is accompanied by at least 1 of the following:

1. Ipsilateral conjunctival injection and/or lacrimation

2. Ipsilateral nasal congestion and/or rhinorrhoea
3. Ipsilateral eyelid oedema
4. Ipsilateral forehead and facial sweating
5. Ipsilateral miosis and/or ptosis
6. A sense of restlessness or agitation

D. Attacks have a frequency from 1 every other day to 8/day

E. Not attributed to another disorder

60
Episodic cluster headache

A. Attacks fulfilling criteria A-E for "Cluster headache"

B. At least two cluster periods lasting 7-365 days and separated by pain-free remission periods of >/=1
month

Chronic cluster headache

A. Attacks fulfilling criteria A-E for "Cluster headache"

B. Attacks recur over >1 year without remission periods or with remission periods lasting <1 month

Diagnostic Criteria for Chronic Fatigue Syndrome (CFS)

Centers for Disease Control Diagnostic Criteria

Clinically evaluated, unexplained, persistent, or relapsing fatigue that is:

Of new or definite onset

Not a result of ongoing exertion
Not alleviated by rest
Results in a substantial reduction in previous levels of occupational, social, or personal activity

Four or more of the following symptoms that persist or recur during 6 or more consecutive months of
illness and that do not predate the fatigue:

Self-reported impairment of short-term memory or concentration

Sore throat
Tender lymph nodes
Muscle pain
Multijoint pain without swelling or redness
Headaches of a new type, pattern, or severity
Unrefreshing and/or interrupted sleep
Postexertion malaise (a feeling of general discomfort or uneasiness) lasting more than 24 hours

Exclusion criteria:

Active, unresolved or suspected disease that is likely to cause fatigue

Psychotic, melancholic, or bipolar depression (but not uncomplicated major depression)
Psychotic disorders
Dementia
Anorexia or bulimia nervosa
Alcohol or other substance misuse
Severe obesity (body mass index equal to or greater than 45)

61
Oxford Diagnostic Criteria

Severe, disabling fatigue of at least six months' duration that:

affects both physical and mental functioning

was present for more than 50% of the time

Other symptoms, particularly myalgia and sleep and mood distrubance, may be present

Exclusion criteria

Active, unresolved, or suspected disease likely to cause fatigue

Psychotic, melancholic or bipolar depression (but not uncomplicated major depression)
Psychotic disorders
Dementia
Anorexia or bulimia nervosa

ICHD-II Diagnostic Criteria for Tension-type headache (TTH)

Infrequent episodic tension-type headache

A. At least 10 episodes occurring on <1 day/month on average (<12 days/year) and fulfilling criteria B-D

B. Headache lasting from 30 minutes to 7 days

C. Headache has at least 2 of the following characteristics:

1. Bilateral location
2. Pressing/tightening (non-pulsating) quality
3. Mild or moderate intensity
4. Not aggravated by routine physical activity such as walking or climbing stairs

D. Both of the following:

1. No nausea or vomiting (anorexia may occur)

2. No more than one of photophobia or phonophobia

E. Not attributed to another disorder

Frequent episodic tension-type headache

As "Infrequent episodic tension-type headache" except:

A. At least 10 episodes occurring on >/=1 but <15 days/month for ?3 months (>/=12 and <180 days/year)
and fulfilling criteria B-D

62
Chronic tension-type headache

As "Infrequent episodic tension-type headache" except:

A. Headache occurring on >/=15 days/month on average for >3 months (>/=180 days/year) and fulfilling
criteria B-D

B. Headache lasts hours or may be continuous

D. Both of the following:

1. No more than one of photophobia, phonophobia or mild nausea

2. Neither moderate or severe nausea nor vomiting

Diagnostic Criteria for Osteoporosis

Osteoporosis is defined as a metabolic bone disease "characterized by low bone mass and
microarchitectural deterioration of bony tissue leading to enhanced bone fragility and a consequent increase
in fracture risk.

World Health Organization (WHO) definition of osteoporosis is only applicable (at present) to Bone
Mineral Density (BMD) measurements using DXA (Dual X-ray Absorptiometry)

BMD as measured by DXA is expressed as absolute BMD (g/cm2) and may be designated by either the
number of standard deviations (SD) from the young normal mean (T score). The WHO developed
guidelines for their use in the clinical diagnosis of osteoporosis and is based on the T score, with a T score
of less than -1.0 being defined as osteopenic and a T score of less than -2.5 being referred as osteoporotic.

WHO Criteria for Osteoporosis

Category Fracture Risk Action

Normal
BMD < 1 SD below youngadult
reference range
Osteopenia
BMD 1-2.5 SD below young adult
reference range
Osteoporosis
BMD > 2.5 SD below young adult
reference mean
Severe Osteoporosis
BMD > 2.5 SD below young adult osteoporosis
reference mean, plus 1 or more
fragility fractures
Below average Be watchful for "clinical triggers"
Above average Consider prevention in peri/postmenopausal in
women.
Be watchful for clinical triggers.
Possibly repeat investigations in 2-3 years.
High Exclude secondary causes.
Therapeutic intervention indicated in most
patients.
Established Exclude secondary causes.
Therapeutic intervention indicated in most
patients.

Diagnostic Criteria for Meniere's Disease

Menieres disease is defined as recurrent, spontaneous episodic vertigo, hearing loss, aural fullness and
tinnitus. Recurrent endolymphatic hypertension (hydrops) is believed to cause the episodes.

63
According to the guidelines from AAO-HNS Committee of Hearing and Equilibrium the three major
symptoms are described as follows:

Vertigo
Recurrent, well-defined episodes of spinning or rotation
Duration ranging from 20 min to 24 h
Nystagmus associated with attacks
Nausea and vomiting during vertigo spells common
No neurologic symptoms with vertigo
Deafness
Hearing deficits fluctuate
Sensorineural hearing loss
Hearing loss progressive, usually unilateral
Tinnitus
Variable, often low pitched and louder during attacks
Usually unilateral on the affected side
Subjective

Diagnosis of Meniere's Disease

Possible Meniere's disease

Episodic vertigo of the Meniere's type without documented hearing loss, or
Sensorineural hearing loss, fluctuating or fixed, with dysequilibrium but without definitive episodes
Other causes excluded

Probable Meniere's disease

One definitive episode of vertigo
Audiometrically documented hearing loss on at least one occasion
Tinnitus or aural fullness in the treated ear
Other causes excluded

Definite Meniere's disease

Two or more definitive spontaneous episodes of vertigo 20 minutes or longer
Audiometrically documented hearing loss on at least one occasion
Tinnitus or aural fullness in the treated ear
Other cases excluded

Certain Meniere's disease

Definite Meniere's disease, plus histopathologic confirmation

Diagnostic Criteria for Benign Paroxysmal Positional Vertigo

Vertigo associated with a characteristic mixed torsional and vertical nystagmus provoked by the
Dix-Hallpike test
A latency (typically of 1 to 2 seconds) between the completion of the Dix-Hallpike test and the
onset of vertigo and nystagmus
Paroxysmal nature of the provoked vertigo and nystagmus (i.e., an increase and then a decline
over a period of 10 to 20 seconds)
Fatigability (i.e., a reduction in vertigo and nystagmus if the Dix-Hallpike test is repeated)

Common Causes of Vertigo

64
Otologic disorders
Benign paroxysmal positional vertigo
Menieres disease (hydrops endolymphayic)
Vestibular neuronitis (labyrinthitis)
Neurologic disorders
Migraine-associated dizziness
Vertebrobasilar insufficiency
Panic disorders

Dix-Hallpike Maneover for Positional Nystagmus

Peripheral disorder Central disorder

Latent period before onset of
positional nystagmus
Duration of nystagmus
Fatigability
Direction of nystagmus
Intensity of vertigo
2 to 20 seconds
Less than 1 minute
Fatiguing with repetition
Only one type, usually
horizontal/rotatory
Severe
None
Greater than 1 minute
Nonfatiguing
May change direction with a given
head position
Less severe, sometimes none

yndromes or Disease Entities That Have Been Associated with Polycystic Ovaries

Hyperandrogenism
o Steroidogenic enzyme deficiencies
Congenital adrenal hyperplasia
Aromatase deficiency
o Androgen-secreting tumors
Ovarian
Adrenal
o Exogenous androgens
Anabolic steroids
Transsexual hormone replacement
o Other
Acne
Idiopathic hirsutism
Hyperandrogenism and Insulin Resistance
o Congenital
Type A syndrome
Type B syndrome
Leprechaunism
Lipoatrophic diabetes
Rabson-Mendenhall syndrome
Polycystic ovary syndrome
o Acquired
Cushing's syndrome
Insulin Resistance
o Glycogen storage diseases
o Type 2 diabetes
Other
o Central nervous system
Trauma/lesions

65
 Hyperprolactinemia
o Nonhormonal medications
Valproate
o Heriditary angioedema
o Bulimia
o Idiopathic (includes normoandrogenic women with cyclic menses)

DSM-IV Diagnostic Criteria for Panic Attack

A discrete period of intense fear or discomfort, in which four (or more) of the following symptoms
developed abruptly and reached a peak within 10 minutes:

1) palpitations, pounding heart, or accelerated heart rate

2) sweating
3) trembling or shaking
4) sensations of shortness of breath or smothering
5) feeling of choking
6) chest pain or discomfort
7) nausea or abdominal distress
8) feeling dizzy, unsteady, lightheaded, or faint
9) derealization (feelings of unreality) or depersonalization (being detached from oneself)
10) fear of losing control or going crazy
11) fear of dying
12) paresthesias (numbness or tingling sensations)
13) chills or hot flushes

Glasgow Coma Score

The Glasgow Coma Scale provides a score in the range 3-15; patients with scores of 3-8 are usually said to
be in a coma. The total score is the sum of the scores in three categories. For adults the scores are as
follows:

Response Spontaneous: open with blinking at baseline 4 points

Opens to verbal command, speech, or shout 3 points
Eye Opening
Opens to pain, not applied to face 2 points
None 1 point
Oriented 5 points
Confused conversation, but able to answer questions 4 points
Verbal Response Inappropriate responses, words discernible 3 points
Incomprehensible speech 2 points
None 1 point
Obeys commands for movement 6 points
Purposeful movement to painful stimulus 5 points
Withdraws from pain 4 points
Motor Response
Abnormal (spastic) flexion, decorticate posture 3 points
Extensor (rigid) response, decerebrate posture 2 points
None 1 point

66
The Mini-Mental Status Examination (MMSE)

Points
Orientation
Name: season/date/day/month/year 5 (1 for each name)
Name: hospital/floor/town/state/country 5 (1 for each name)
Registration
Identify three objects by name and ask patient to repeat 3 (1 for each object)
Attention and calculation
Serial 7s; subtract from 100 (e.g., 93-86-79-72-65) 5 (1 for each subtraction)
Recall
Recall the three objects presented earlier 3 (1 for each object)
Language
Name pencil and watch 2 (1 for each object)
Repeat No ifs, ands, or buts 1
Follow a 3-step command (e.g., Take this paper, fold it in half, and 3 (1 for each command)
place it on the table)
Write close your eyes and ask patient to obey written command 1
Ask patient to write a sentence
Ask patient to copy a design (e.g., intersecting pentagons) 1
1
TOTAL 30

The MMSE is an easily administered 30-point test of cognitive function and contains tests of orientation,
working and episodic memory, language comprehension, naming, and copying.

cDonald Diagnostic Criteria for Multiple Sclerosis (MS)

What Is An Attack?

Neurological disturbance of kind seen in MS

Subjective report or objective observation
24 hours duration, minimum
Excludes pseudoattacks, single paroxysmal episodes

Determining Time Between Attacks

30 days between onset of event 1 and onset of event 2

How Is "Abnormality" In Paraclinical Tests Determined?

A- Magnetic resonance imaging (MRI): Three out of four:

1 Gd-enhancing or 9 T2 hyperintense lesions if no Gd-enhancing lesion

1 or more infratentorial lesions
1 or more juxtacortical lesions
3 or more periventricular lesions

67
 (1 spinal cord lesion = 1 brain lesion)

B- Cerebrospinal fluid (CSF)

Oligoclonal IgG bands in CSF (and not serum)

or elevated IgG index

C- Evoked potentials (EP)

Delayed but well-preserved wave form

What Provides MRI Evidence Of Dissemination In Time?

A Gd-enhancing lesion demonstrated in a scan done at least 3 months following onset of clinical attack at a
site different from attack,
or
In absence of Gd-enhancing lesions at 3 month scan, follow-up scan after an additional 3 months showing
Gd-lesion or new T2 lesion.

Steps in Making a Diagnosis of MS

Clinical Presentation
2 or more attacks (relapses)
2 or more objective clinical lesions
2 or more attacks
1 objective clinical lesion
1 attack
2 or more objective clinical lesions
1 attack
1 objective clinical lesion
(monosymptomatic presentation)
Additional Data Needed
None; clinical evidence will suffice
(additional evidence desirable but must be consistent with MS)
Dissemination in space, demonstrated by:
MRI
or a positive CSF and 2 or more MRI lesions consistent with MS
or further clinical attack involving different site
Dissemination in time, demonstrated by:
MRI
or second clinical attack
Dissemination in space, demonstrated by:
MRI
or positive CSF and 2 or more MRI lesions consistent with MS
and

Dissemination in time demonstrated by:

MRI
or second clinical attack
Insidious neurological progression Positive CSF
suggestive of MS
(primary progressive MS) and

Dissemination in space demonstrated by:

MRI evidence of 9 or more T2 brain lesions
or 2 or more spinal cord lesions
or 4-8 brain and 1 spinal cord lesion
or positive VEP with 4-8 MRI lesions
or positive VEP with <4 brain lesions plus 1 spinal cord lesion

and

68
 Dissemination in time demonstrated by:
MRI
or continued progression for 1 year

Diagnostic Criteria for Myasthenia Gravis

Neuromuscular transmission disorder characterized by fluctuating weakness and fatigability of bulbar and
other voluntary muscles without loss of reflexes or impairment of sensation or other neurologic function.

Diagnostic criteria:

A. Characteristic signs and symptoms

One or more of the following:

1. Diplopia, ptosis, dysarthria, weakness in chewing, difficulty in swallowing, muscle weakness with
preserved deep tendon reflexes, and, less commonly, weakness of neck extension and flexion, and
weakness of trunk muscles
2. Increased weakness during exercise and repetitive use with at least partially restored strength after
periods of rest
3. Dramatic improvement in strength following administration of anticholinesterase drug
(edrophonium (Tensiln) and neostigmine);

and one or more of the following:

B. EMG and repetitive stimulation of a peripheral nerve: In myasthenia gravis repetitive stimulation at a
rate of 2 per second shows characteristic decremental response which is reversed by edrophonium or
neostigmine. Single fiber studies show increased jitter.

C. Antibodies to Acetylcholine Receptors

Exclusions:

Congenital myasthenic syndrome, progressive restricted myopathies, steroid and inflammatory

myopathies, motor neuron disease
Multiple sclerosis, variants of Guillain-Barr syndrome (e.g., Miller-Fisher syndrome)
Organophosphate toxicity, botulism, black widow spider venom
Eaton-Lambert syndrome
Stroke
Medications: neuromuscular blocking agents, aminoglycosides, penicillamine, antimalarial drugs,
colistin, streptomycin, polymyxin B, tetracycline
Hypokalemia; hypophosphatemia

Severity: (Osserman classification):

I: Ocular myasthenia
IIA: Mild generalized myasthenia with slow progression: no crises, responsive to drugs
IIB. : Moderately severe generalized myasthenia : severe skeletal and bulbar involvement but no crises;
drug response less than satisfactory
III: Acute fulminating myasthenia, rapid progression of severe symptoms, with respiratory crises and poor

69
drug response
IV: Late severe myasthenia, same as III but progression over 2 years from class I to II

The Oswestry Disability Index (ODI) Version 2.0 or Oswestry Low Back Pain Disability
Questionnaire

Section 1: Pain Intensity

I can tolerate the pain I have without having to use pain killers. [0 points]
The pain is bad but I manage without taking pain killers. [1 point]
Pain killers give complete relief from pain . [2 points]
Pain killers give moderate relief from pain. [3 points ]
Pain killers give very little relief from pain. [4 points]
Pain killers have no effect on the pain and I do not use them. [5 points]

Section 2: Personal Care

I can look after myself normally without causing extra pain. [0 points]
I can look after myself normally but it causes extra pain. [1 point]
It is painful to look after myself and I am slow and careful. [2 points]
I need some help but manage most of my personal care. [3 points]
I need help every day in most aspects of self care. [4 points]
I do not get dressed wash with difficulty and stay in bed. [5 points]

Section 3: Lifting

I can lift heavy weights without extra pain. [0 points]

I can lift heavy weights but it gives extra pain. [1 point]
Pain prevents me from lifting heavy weights off the floor but I can manage if they are
conveniently positioned for example on a table. [2 points]
Pain prevents me from lifting heavy weights but I can manage light to medium weights if they are
conveniently positioned. [3 points]
I can lift only very light weights. [4 points]
I cannot lift or carry anything at all. [5 points]

Section 4: Walking

Pain does not prevent me walking any distance. [0 points]

Pain prevents me walking more than 1 mile. [1 point]
Pain prevents me walking more than 0.5 miles. [2 points]
Pain prevents me walking more than 0.25 miles. [3 points]
I can only walk using a stick or crutches. [4 points]
I am in bed most of the time and have to crawl to the toilet. [5 points]

Section 5: Sitting

I can sit in any chair as long as I like. [0 points]

70
 I can only sit in my favorite chair as long as I like. [1 point]
Pain prevents me sitting more than 1 hour. [2 points]
Pain prevents me from sitting more than 0.5 hours. [3 points]
Pain prevents me from sitting more than 10 minutes. [4 points]
Pain prevents me from sitting at all. [5 points]

Section 6: Standing

I can stand as long as I want without extra pain. [0 points]

I can stand as long as I want but it gives me extra pain. [1 point]
Pain prevents me from standing for more than 1 hour. [2 points]
Pain prevents me from standing for more than 30 minutes. [3 points]
Pain prevents me from standing for more than 10 minutes. [4 points]
Pain prevents me from standing at all. [5 points]

Section 7: Sleeping

Pain does not prevent me from sleeping well. [0 points]

I can sleep well only by using tablets. [1 point]
Even when I take tablets I have less than 6 hours sleep. [2 points]
Even when I take tablets I have less than 4 hours sleep. [3 points]
Even when I take tablets I have less than 2 hours of sleep. [4 points]
Pain prevents me from sleeping at all. [5 points]

Section 8: Sex Life

My sex life is normal and causes no extra pain. [0 points]

My sex life is normal but causes some extra pain. [1 point]
My sex life is nearly normal but is very painful. [2 points]
My sex life is severely restricted by pain. [3 points]
My sex life is nearly absent because of pain. [4 points]
Pain prevents any sex life at all. [5 points]

Section 9: Social Life

My social life is normal and gives me no extra pain. [0 points]

My social life is normal but increases the degree of pain. [1 point]
Pain has no significant effect on my social life apart from limiting energetic interests such as
dancing. [2 points]
Pain has restricted my social life and I do not go out as often. [3 points]
Pain has restricted my social life to my home. [4 points]
I have no social life because of pain. [5 points]

Section 10: Traveling

I can travel anywhere without extra pain. [0 points]

I can travel anywhere but it gives me extra pain. [1 point]
Pain is bad but I manage journeys over 2 hours. [2 points]
Pain restricts me to journeys of less than 1 hour. [3 points]
Pain restricts me to short necessary journeys under 30 minutes. [4 points]
Pain prevents me from traveling except to the doctor or hospital. [5 points]

71
Interpretation:

Now, simply add up your points for each section and plug it in to the following formula in order to
calculate your level of disability: point total / 50 X 100 = % disability (aka: 'point total' divided by '50'
multiply by ' 100 = percent disability)

Example: on my last ODI I scored a 16. So, 16/50 x 100 = 32% disability:

ODI Scoring:

0% to 20% (minimal disability): Patients can cope with most activities of daily living. No
treatment may be indicated except for suggestions on lifting, posture, physical fitness and diet.
Patients with sedentary occupations (ex. secretaries) may experience more problems than others.
21%-40% (moderate disability): Patients may experience more pain and problems with sitting,
lifting and standing. Travel and social life are more difficult. Patients may be off work. Personal
care, sleeping and sexual activity may not be grossly affected. Conservative treatment may be
sufficient.
41%-60% (severe disability): Pain is a primary problem for these patients, but they may also be
experiencing significant problems in travel, personal care, social life, sexual activity and sleep. A
detailed evaluation is appropriate.
61%-80% (crippled): Back pain has an impact on all aspects of daily living and work. Active
treatment is required.
81%-100%: These patients may be bed bound or exaggerating their symptoms. Careful
evaluation is recommended.

Diagnostic Criteria for Parkinsons Disease (PD)

United Kingdom Parkinson's Disease Society Brain Bank Diagnostic Criteria for Parkinsons Disease

Step 1: Diagnosis of Parkinsonism

Bradykinesia and at least one of the following:
Muscular rigidity
46 Hz resting tremor
Postural instability not caused by primary visual, vestibular, cerebellar or proprioceptive
dysfunction
Step 2: Features tending to exclude Parkinsons disease as the cause of Parkinsonism
History of repeated strokes with stepwise progression of parkinsonian features
History of repeated head injury
History of definite encephalitis
Neuroleptic treatment at onset of symptoms
>1 affected relatives
Sustained remission
Strictly unilateral features after 3 years
Supranuclear gaze palsy
Cerebellar signs
Early severe autonomic involvement

72
 Early severe dementia with disturbances of memory, language and praxis
Babinski's sign
Presence of a cerebral tumour or communicating hydrocephalus on computed tomography scan
Negative response to large doses of levodopa (if malabsorption excluded)
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure
Step 3: Features that support a diagnosis of Parkinsons disease (three or more required for diagnosis of
definite Parkinsons disease)
Unilateral onset
Rest tremor present
Progressive disorder
Persistent asymmetry affecting the side of onset most
Excellent (70100%) response to levodopa
Severe levodopa-induced chorea
Levodopa response for 5 years
Clinical course of 10 years

Criteria of diagnosis of Parkinson disease (Gelb et al, 1999) commissioned and supported by the
Advisory Council of the National Institute of Neurological Disorders and Stroke, US National
Institutes of Health.

Grouping of clinical features of Parkinsons disease according to diagnostic utility

GROUP A: Features characteristic of Parkinson disease

Resting tremor
Bradykinesia
Rigidity
Asymmetric onset
GROUP B: Features suggestive of alternative diagnoses
Features unusual early in the clinical course
Prominent postural instability in the first 3 years after symptom onset
Freezing phenomena in the first 3 years
Hallucinations unrelated to medications in the first 3 years
Dementia preceding motor symptoms or in the first year
Supranuclear gaze palsy (other than restriction of upward gaze) or slowing of vertical saccades
Severe, symptomatic dysautonomia unrelated to medications
Documentation of a condition known to produce Parkinsonism and plausibly connected to the
patients symptoms (such as suitably located focal brain lesions or neuroleptic use within the past
6 months)

Criteria for POSSIBLE diagnosis of Parkinsons disease

At least 2 of the 4 features in Group A are present; at least 1 of these is tremor or bradykinesia
And either:
none of the features in Group B is present
or symptoms have been present for less than 3 years, and none of the features in Group B is
present to date
And either:
substantial and sustained response to levodopa or a dopamine agonist has been documented
or patient has not had an adequate trial of levodopa or dopamine agonist

73
Criteria for PROBABLE diagnosis of Parkinsons disease

At lest 3 of the 4 features in Group A are present

And none of the features in Group B is present (note: symptom duration of at least 3 years is needed to
meet this requirement)
And substantial and sustained response to levodopa or a dopamine agonist has been documented

Criteria for DEFINITE diagnosis of Parkinsons disease

All criteria for POSSIBLE Parkinson disease are met

And histopathological confirmation of the diagnosis is obtained at autopsy

Proposed criteria for histopathological confirmation of Parkinson disease

Substantial nerve cell depletion with accompanying gliosis in the substantia nigra
At least 1 Lewy body in the substantia nigra or in the locus coeruleus (note: it may be necessary to
examine up to 4 non-overlapping sections in each of these areas before concluding that Lewy
bodies are absent)
No pathological evidence for other diseases that produce Parkinsonism (eg progressive
supranuclear palsy, multiple system atrophy, corticalbasal ganglionic degeneration) (Note: in
excluding other diseases that produce Parkinsonism, published consensus criteria should be used
when available)

Diagnostic Criteria and Associated Features of Restless Legs Syndrome (RLS)

Minimal Criteria

1. A compelling urge to move the limbs, usually associated with paresthesias or dysesthesias
2. Motor restlessness as seen in activities such as floor pacing, tossing and turning in bed and
rubbing the legs
3. Symptoms that are worse or present only during rest and are partially or temporarily relieved by
activity
4. Symptoms that are worse in the evening and at night

Associated Features

1. Sleep disturbance and daytime fatigue

2. Normal neurologic examination (in patients with primary RLS)
3. Involuntary, repetitive, periodic, jerking limb movements, either in sleep or while awake and at
rest

Diagnostic Criteria for Tuberous Sclerosis Complex (TSC)

74
The diagnostic criteria for tuberous sclerosis complex (TSC) were revised at the Tuberous Sclerosis
Complex Consensus Conference, July 1998.

Definite TSC: Two major features or one major feature plus two minor features

Probable TSC: One major feature plus one minor feature

Possible TSC: One major feature or two or more minor features

Major Features

Facial angiofibromas or forehead plaque

Nontraumatic ungual or periungual fibromas
Hypomelanotic macules (three or more)
Shagreen patch (connective tissue nevus)
Multiple retinal nodular hamartomas
Cortical tuber 1
Subependymal nodule
Subependymal giant cell astrocytoma
Cardiac rhabdomyoma, single or multiple
Lymphangiomyomatosis 2
Renal angiomyolipoma 2

Minor Features

Multiple randomly-distributed pits in dental enamel

Hamartomatous rectal polyps
Bone cysts
Cerebral white matter radial migration lines 1,3
Gingival fibromas
Nonrenal hamartoma
Retinal achromic patch
"Confetti" skin lesions
Multiple renal cysts

1. Cerebral cortical dysplasia and cerebral white matter migration tracts occurring together are counted as
one rather than two features of TSC.
2. When both lymphangiomyomatosis and renal angiomyolipomas are present, other features of tuberous
sclerosis must be present before TSC is diagnosed.
3. White matter migration lines and focal cortical dysplasia are often seen in individuals with TSC;
however, because these lesions can be seen independently and are relatively nonspecific, they are
considered a minor diagnostic criteria for TSC.

Diagnostic Criteria for HELLP Syndrome

The diagnosis of HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) is based
upon the presence of the characteristic laboratory findings in patients of appropriate gestational age.
Imaging tests, particularly CT or MRI scanning, are useful when complications such as hepatic infarction,
hematoma, or rupture are suspected.

75
The diagnosis is established by the presence of preeclampsia and the following criteria:

Microangiopathic hemolytic anemia with characteristic schistocytes on blood smear

Platelet count <100,000 cells/L
Serum lactate dehydrogenase >600 IU/L or total bilirubin >1.2 mg/dL
Serum aspartate aminotransferase (AST) >70 IU/L

Diagnostic Criteria for Preeclampsia

Preeclampsia: For the diagnosis of preeclampsia, both hypertension and proteinuria must be present.

Blood pressure: 140 mm Hg or higher systolic or 90 mm Hg or higher diastolic after 20 weeks of

gestation in a woman with previously normal blood pressure. Systolic increased > 30 mm Hg or
diastolic increased > 15 mm Hg in a patient with preexisting chronic hypertension.
Proteinuria: 0.3 g or more of protein in a 24-hour urine collection (usually corresponds with 1+ or
greater on a urine dipstick test)

Severe preeclampsia

Blood pressure: 160 mm Hg or higher systolic or 110 mm Hg or higher diastolic on two occasions
at least six hours apart in a woman on bed rest
Proteinuria: 5 g or more of protein in a 24-hour urine collection or 3+ or greater on urine dipstick
testing of two random urine samples collected at least four hours apart
Other features: oliguria (less than 500 mL of urine in 24 hours), cerebral or visual disturbances,
pulmonary edema or cyanosis, epigastric or right upper quadrant pain, impaired liver function,
thrombocytopenia, intrauterine growth restriction

Risk Factors for Preeclampsia

Pregnancy-associated factors

Chromosomal abnormalities
Hydatidiform mole
Hydrops fetalis
Multifetal pregnancy
Oocyte donation or donor insemination
Structural congenital anomalies
Urinary tract infection

Maternal-specific factors

Age greater than 35 years

Age less than 20 years
Black race
Family history of preeclampsia
Nulliparity
Preeclampsia in a previous pregnancy
Specific medical conditions: gestational diabetes, type I diabetes, obesity, chronic hypertension,
renal disease, thrombophilias
Stress

76
Paternal-specific factors

First-time father
Previously fathered a preeclamptic pregnancy in another woman

Revised Criteria for Hereditary Non-Polyposis Colorectal Cancer (Lynch Syndrome)

Amsterdam Criteria (1991)

Three or more relatives with colorectal cancer, plus all of the following:
One affected patient should be a first-degree relative of the other two;
Colorectal cancer should involve at least two generations;
At least one case of colorectal cancer should have been diagnosed before the age of 50 years.

Amsterdam II Criteria (Revised International Collaborative Group on Hereditary Non-Polyposis

Colorectal Cancer (HNPCC) Criteria 1998)
Three or more relatives with HNPCC-associated cancer (colorectal cancer or cancer of the endometrium,
small bowel, ureter or renal pelvis) plus all of the following:
One affected patient should be a first-degree relative of the other two;
Two or more successive generations should be affected;
Cancer in one or more affected relatives should be diagnosed before the age of 50 years;
Familial adenomatous polyposis should be excluded in any cases of colorectal cancer;
Tumours should be verified by pathological examination.

Modified Amsterdam Criteria

Just one of these criteria need to be met:
Very small families, which can not be further expanded, can be considered to have HNPCC with
only two colorectal cancers in first-degree relatives if at least two generations have the cancer and
at least one case of colorectal cancer was diagnosed by the age of 55 years;
In families with two first-degree relatives affected by colorectal cancer, the presence of a third
relative with an unusual early-onset neoplasm or endometrial cancer is sufficient.

Revised Bethesda Criteria (2003)

Just one these criteria need to be met:
Diagnosed with colorectal cancer before the age of 50 years;
Synchronous or metachronous colorectal or other HNPCC-related tumours (which include
stomach, bladder, ureter, renal pelvis, biliary tract, brain (glioblastoma), sebaceous gland
adenomas, keratoacanthomas and carcinoma of the small bowel), regardless of age;
Colorectal cancer with a high-microsatellite instability morphology that was diagnosed before the
age of 60 years;
Colorectal cancer with one or more first-degree relatives with colorectal cancer or other HNPCC-
related tumours. One of the cancers must have been diagnosed before the age of 50 years (this
includes adenoma, which must have been diagnosed before the age of 40 years);
Colorectal cancer with two or more relatives with colorectal cancer or other HNPCC-related
tumours, regardless of age.

umor, Node, Metastasis International Staging System for Lung Cancer

Stage TNM Descriptors 5-Year Survival Rate, %

Clinical Stage Surgical-Pathologic Stage
IA T1 N0 M0 61 67
IB T2 N0 M0 38 57

77
IIA T1 N1 M0 34 55
IIB T2 N1 M0 24 39
IIB T3 N0 M0 22 38
IIIA T3 N1 M0 9 25
T123 N2 M0 13 23
IIIB T4 N012 M0 7 <5
T1234 N3 M0 3 <3
IV Any T any N M1 1 <1

TUMOR (T) STATUS

T0 No evidence of a primary tumor

TX Primary tumor cannot be assessed, or tumor proven by the presence of malignant cells in
sputum or bronchial washings but not visualized by imaging or bronchoscopy
TIS Carcinoma in situ
T1 Tumor <3 cm in greatest dimension, surrounded by lung or visceral pleura, without
bronchoscopic evidence of invasion more proximal than lobar bronchus (i.e., not in main
bronchus)
T2 Tumor with any of following: >3 cm in greatest dimension; involves main bronchus, >2 cm
distal to the carina; invades visceral pleura; associated with atelectasis or obstructive pneumonitis
extending to hilum but does not involve entire lung
T3 Tumor of any size that directly invades any of the following: chest wall (including superior
sulcus tumors), diaphragm, mediastinal pleura, parietal pericardium; or tumor in main bronchus <2
cm distal to carina but without involvement of carina; or associated atelectasis or obstructive
pneumonitis of entire lung
T4 Tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea,
esophagus, vertebral body, carina; or tumor with a malignant pleural or pericardial effusion a, or
with satellite tumor nodule(s) within the ipsilateral primary-tumor lobe of the lung.

LYMPH NODE (N) INVOLVEMENT

NX Regional lymph nodes cannot be assessed

N0 No regional lymph node metastasis
N1 Metastasis to ipsilateral peribronchial and/or ipsilateral hilar lymph nodes, and intrapulmonary
nodes involved by direct extension of the primary tumor
N2 Metastasis to ipsilateral mediastinal and/or subcarinal lymph nodes(s)
N3 Metastasis to contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene,
or supraclavicular lymph node(s)

DISTANT METASTASIS (M)

MX Presence of distant metastasis cannot be assessed

M0 No distant metastasis
M1 Distant metastasis presentb

a
Most pleural effusions associated with lung cancer are due to tumor. However, in a few patients with
multiple negative cytopathologic exams of a non-bloody, non-exudative pleural or pericardial effusion that
clinical judgment dictates is not related to the tumor, the effusion should be excluded as a staging element
and the patients disease staged as T1, T2, or T3.

b
Separate metastatic pulmonary tumor nodule(s) in the ipsilateral nonprimary tumor lobe(s) of the lung are
classified as M1.

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Light Criteria for Exudative Pleural Effusion

Transudative and exudative pleural effusions are distinguished by measuring the lactate dehydrogenase
(LDH) and protein levels in the pleural fluid. Exudative pleural effusions meet at least one of the following
criteria, whereas transudative pleural effusions meet none:

1. pleural fluid protein/serum protein >0.5

2. pleural fluid LDH/serum LDH >0.6

3. pleural fluid LDH more than two-thirds normal upper limit for serum

The above criteria misidentify approximately 25% of transudates as exudates. If one or more of the
exudative criteria are met and the patient is clinically thought to have a condition producing a transudative
effusion, the difference between the albumin levels in the serum and the pleural fluid should be measured.
If this gradient is greater than 12 g/L (1.2 g/dL), the exudative categorization by the above criteria can be
ignored because almost all such patients have a transudative pleural effusion.

If a patient has an exudative pleural effusion, the following tests on the pleural fluid should be obtained:
description of the fluid, glucose level, differential cell count, microbiologic studies, and cytology.

Diagnosis, Clinical Characteristics, and Treatment of Sarcoidosis

Diagnosis

Diagnosis of sarcoidosis is firm when chest radiographic evidence is accompanied by compatible

clinical features and noncaseating granulomas on biopsy, with all other causes of granulomas ruled
out.
Biopsy is indicated for all patients presumed to have sarcoidosis, except those with Lfgrens
syndrome.
Pathologists can identify granulomas, but the diagnosis should not be based on pathological
findings alone.
A response to corticosteroid therapy does not establish the diagnosis of sarcoidosis.
Measurement of the serum angiotensin-convertingenzyme level is an insensitive and nonspecific
diagnostic test and a poor therapeutic guide.
For patients without apparent lung involvement, FDG PET is useful in identifying sites for
diagnostic biopsy.
FDG PET and MRI with gadolinium detect cardiac and neurologic involvement. (Caution in the
use of gadolinium is needed, given the possibility that nephrogenic fibrosing sclerosis may
develop in patients with chronic kidney disease.)
CT imaging is unnecessary for most patients with sarcoidosis. CT is indicated when the chest
radiograph is atypical for sarcoidosis or when hemoptysis occurs.

Clinical characteristics

Constitutional symptoms such as fatigue may predominate.

Cardiac sarcoidosis is much more common than reported previously and may cause loss of
ventricular function and sudden death.
Cardiac and neurologic sarcoidosis may occur without apparent disease activity in other organs.
Chest radiographic patterns (stages 1, 2, and 3) do not reflect the chronology of the disease.

79
Treatment

Most patients with sarcoidosis do not require therapy.

There have been few well-controlled studies of the use of any therapeutic agent in patients with
sarcoidosis be skeptical of anecdotal reports.
Treatment for pulmonary sarcoidosis is best guided by pulmonary-function studies.
Deforming sarcoidal skin lesions are usually chronic and require prolonged therapy.

Abbreviations: FDG PET denotes 18F-fluorodeoxyglucose positron-emission tomography, MRI magnetic

resonance imaging, and CT computed tomography.

Diagnostic Criteria for Autoimmune Hepatitis (AIH)

Requisites Diagnostic Criteria

Definite Probable
No genetic liver disease Normal alpha1 antitrypsin Partial alpha1 antitrypsin deficiency
phenotype Nonspecific serum copper,
Normal serum ceruloplasmin, iron, ceruloplasmin, iron, and/or ferritin
and ferritin levels abnormalities
No active viral infection No markers of current infection with No markers of current infection with
hepatitis A, B, and C viruses hepatitis A, B, and C viruses
No toxic or alcohol injury Daily alcohol < 25 g/d and no recent Daily alcohol < 50 g/d and no recent
use of hepatotoxic drugs use of hepatotoxic drugs
Laboratory features Predominant serum Predominant serum aminotransferase
aminotransferase abnormality abnormality
Globulin, gamma-globulin or Hypergammaglobulinemia of any
immunoglobulin G level >/= 1.5 degree
times normal
Autoantibodies ANA, SMA, or anti-LKM1 >/= 1:80 ANA, SMA, or anti-LKM1 >/= 1:40
in adults and >/=1:20 in children; no in adults or other autoantibodies*
AMA
Histologic findings Interface hepatitis Interface hepatitis
No biliary lesions, granulomas, or No biliary lesions, granulomas, or
prominent changes suggestive of prominent changes suggestive of
another disease another disease
Abbreviation: AMA, antimitochondrial antibodies.
*Includes perinuclear anti-neutrophil cytoplasmic antibodies and the not generally available antibodies to
soluble liver antigen/liver pancreas, actin, liver cytosol type 1, and asialoglycoprotein receptor.

Diagnostic Scoring System for Atypical Autoimmune Hepatitis in Adults

Category Factor Score

Gender Female +2
>3 -2
Alk Phos:AST (or ALT) ratio
<1.5 +2
>2.0 +3
Gamma-globulin or IgG (times 1.5-2.0 +2
above upper limit of normal) 1.0-1.5 +1
<1.0 0

80
 >1:80 +3
1:80 +2
ANA, SMA, or anti-LKM1 titers
1:40 +1
<1:40 0
AMA Positive -4
Positive -3
Viral markers of active infection
Negative +3
Yes -4
Hepatotoxic drugs
No +1
<25 g/d +2
Alcohol
>60 g/d -2
Any nonhepatic disease of an
Concurrent immune disease +2
immune nature
Other autoantibodies* Anti-SLA/LP, actin, LC1, pANCA +2
Interface hepatitis +3
Plasma cells +1
Rosettes +1
Histologic features
None of above -5
Biliary changes -3
Atypical features -3
HLA DR3 or DR4 +1
Remission alone +2
Treatment response
Remission with relapse +3
Pretreatment score
Definite diagnosis >15
Probable diagnosis 10-15
Posttreatment score
Definite diagnosis >17
Probable diagnosis 12-17

Abbreviations: Alk phos, serum alkaline phosphatase level; AST, serum aspartate aminotransferase level;
ALT, serum alanine aminotransferase level; IgG, serum immunoglobulin G level; AMA, antimitochondrial
antibodies; HLA, human leukocyte antigen.

Names and definitions of vasculitis adopted by the Chapel Hill Consensus Conference

Names and definitions of vasculitis adopted by the Chapel Hill Consensus Conference on the nomenclature
of systemic vasculitis

1. Polyarteritis nodosa (PAN): Necrotizing inflammation of medium-sized or small arteries without

glomerulonephritis or vasculitis in arterioles, capillaries or venules.
2. Wegeners granulomatosis (WG): Granulomatous inflammation involving the respiratory tract,
and necrotizing vasculitis affecting small to medium-sized vessels, e. g. capillaries, venules,
arterioles and arteries. Necrotizing glomerulonephritis is common.
3. Churg-Strauss syndrome (CSS): Eosinophil-rich and granulomatous inflammation involving the
respiratory tract and necrotizing vasculitis affecting small to medium-sized vessels, and associated
with asthma and blood eosinophilia.

81
 4. Microscopic polyangiitis (MSA): Necrotizing vasculitis with few or no immune deposits affecting
small vessels, i.e. capillaries, venules or arterioles. Necrotizing arteritis of small and medium-sized
arteries may be present. Necrotizing glomerulonephritis is very common. Pulmonary capillaritis
often occurs.

ACR Criteria for the Classification of Churg-Strauss Syndrome (CSS)

American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (CSS).
Classified as CSS if at least four of six criteria are present

1. Asthma: History of wheezing or diffuse high-pitched expiratory rhonchi.

2. Eosinophilia: Eosinophilia >10% on differential white blood cell count.
3. Mono- or polyneuropathy: Development of mononeuropathy, multiple mononeuropathies, or
polyneuropathy (glove/ stocking distribution) attributable to systemic vasculitis.
4. Pulmonary infiltrates, non-fixed: Migratory or transitory pulmonary infiltrates (not including fixed
infiltrates). attributable to vasculitis.
5. Paranasal sinus abnormality: History of acute or chronic paranasal sinus pain or tenderness or
radiographic opacification of the paranasal sinuses.
6. Extravascular eosinophils: Biopsy including artery, arteriole or venule showing accumulations of
eosinophils in extravascular areas.

Criteria for the Classification of Acute Gouty Arthritis

A. Presence of characteristic urate crystals in the joint fluid, or

B. Presence of a tophus proven to contain urate crystals by chemical means or polarized light microscopy,
or
C. Presence of six of the following clinical, laboratory, and radiographic phenomena:
1. More than one attack of acute arthritis.
2. Development of maximal inflammation within 1 day.
3. Attack of monarticular arthritis.
4. Observation of joint redness.
5. Pain or swelling in first metatarsophalangeal joint.
6. Unilateral attack involving first metatarsophalangeal joint.
7. Unilateral attack involving tarsal joint.
8. Suspected tophus.
9. Hyperuricemia.
10. Asymmetric swelling within a joint on x-ray.
11. Subcortical cysts without erosions on x-ray.
12. Negative culture of joint fluid for microorganisms during attack of joint inflammation.

Comparison of Gout and Pseudogout

Gout Pseudogout
Ratio of men to women 7:1 1:1.5
Age group affected Men >40 years old Elderly
Postmenopausal women
Serum urate Elevated Normal
Joints involved First metatarsophalangeal (MTP) Knees, wrists, ankles
joint, insteps, knees, wrists, fingers,
olecranon bursae
Involvement of first MTP Common Rare
(podagra)
Tophi Present Rare tophi-like deposits

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Radiographic findings Erosions with overhanging edges Chondrocalcinosis
Crystals Needle-shaped, strong negative Rhomboid-shaped, weakly positive
birefringence birefringence

Diagnostic Criteria for Mixed Connective Tissue Disease (MCTD)

Alarcon-Segovia Diagnostic Criteria for Mixed Connective Tissue Disease (MCTD)

1. Serological criteria: Positive anti U1 RNP at haemagglutination titer >1:1600

2. Clinical criteria:
a. Oedema of hands
b. Synovitis
c. Myositis
d. Raynauds
e. Acrosclerosis

Requirements:

a. Serological
b. At least 3 clinical features
c. Association of hand oedema, Raynauds and acrosclerosis requires at least one other feature

Kusukawa Diagnostic Criteria for Mixed Connective Tissue Disease (MCTD)

Common Symptoms

1. Reynauds Phenomenon
2. Swollen fingers or hands

Presence of Anti U1 RNP

Mixed findings

A. Systemic lupus erythematosus (SLE) like

Polyarthritis
Pericarditis/pleuritis
Lymphadenopathy
Facial erithema
Leucopenia/thrombocytopenia

B. Scleroderma like

Sclerodactyly
Pulmonary fibrosis
Esophageal dysmotility

C. Polymyositis like

83
 Muscle weakness
High creatine phosphokinase (CPK)
Myophatic electromyogram (EMG)

Requirement for diagnosis: At least one common symptom, with positive U1 RNP antibodies and one or
more findings in at least two of the three categories A, B, and C.
Classification Criteria for Osteoarthritis

ACR Classification Criteria for Osteoarthritis of the Hip

Traditional format
Hip pain plus at least two of the following:
ESR of less than 20 mm per hour
Femoral or acetabular osteophytes on radiographs
Joint space narrowing on radiographs

Classification-tree format
Hip pain plus femoral or acetabular osteophytes on radiographs
or
Hip pain plus joint space narrowing on radiographs and an ESR of less than 20 mm per hour

ESR = erythrocyte sedimentation rate.

ARA Classification Criteria for Idiopathic Osteoarthritis of the Knee

Traditional format
Knee pain plus osteophytes on radiographs and at least one of the following:
Patient age older than 50 years
Morning stiffness lasting 30 minutes or less
Crepitus on motion

Classification-tree format
Knee pain and osteophytes on radiographs
or
Knee pain plus patient age of 40 years or older, morning stiffness lasting 30 minutes or less and crepitus on
motion

ACR Classification Criteria for Osteoarthritis of the Hand

Hand pain, aching or stiffness

plus
Hard tissue enlargement of two or more of 10 selected joints*
plus
Fewer than three swollen metacarpophalangeal joints
plus
Hard tissue enlargement of two or more distal interphalangeal joints
or
Deformity of two or more of 10 selected joints*

* - 10 selected joints are the second and third distal interphalangeal joints, the second and third proximal
interphalangeal joints and the first carpometacarpal joints (of both hands).

84
ACR Criteria for the Classification of Polyarteritis Nodosa (PAN)

American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa (PAN).
Classified as PAN if at least three of the 10 criteria are present:

1. Weight loss > 4 kg: Loss of >4 kg body weight since illness began, not related to dieting or other
factors.
2. Livedo reticularis: Mottled reticular pattern over the skin of portions of the extremities or torso.
3. Testicular pain/tenderness: Pain or tenderness of the testicles, not due to infection, trauma or other
causes.
4. Myalgias, weakness or leg tenderness: Diffuse myalgias (excluding shoulder or hip girdle) or
weakness of muscles or tenderness of leg muscles.
5. Mono- or polyneuropathy: Development of mononeuropathy, multiple mononeuropathies or
polyneuropathy.
6. Diastolic BP >90 mmHg: Development of hypertension with the diastolic BP higher than 90
mmHg.
7. Elevated BUN or creatinine: Elevation of BUN >40 mg/dl or creatinine >1.5 mg/dl, not due to
dehydration or obstruction.
8. Hepatitis B virus: Presence of hepatitis B surface antigen or antibody in serum.
9. Arteriographic abnormality: Arteriogram showing aneurysms or occlusions of the visceral arteries,
not due to arteriosclerosis, fibromuscular dysplasia or other non-inflammatory causes.
10. Biopsy of small or medium-sized artery containing polymorphonuclear cells: Histologic changes
showing the presence of granulocytes or granulocytes and mononuclear leucocytes in the artery
wall.

These criteria have a reported sensitivity of 82.2% and a reported specificity of 86.6% for the classification
of polyarteritis nodosa compared with other vasculitides.

Diagnostic Criteria for Polymyalgia Rheumatica (PMR)

There is no universally agreed upon or thoroughly validated set of criteria for the diagnosis of PMR. In the
absence of any pathognomonic test, we use the following three criteria for the clinical diagnosis of
PMR(1,2):
1. Age 50 years or older at onset
2. Bilateral aching and morning stiffness (lasting 30 minutes or more) persisting for at least one
month, and involving at least two of the following three areas: neck or torso, shoulders or
proximal regions of the arms, and hips or proximal aspects of the thighs
3. ESR (Westergren) elevated to 40 mm/h or more
Some authors add a prompt response of symptoms to corticosteroids as an additional criterion. On the other
hand, the presence of another disease to explain the findings excludes the diagnosis.

Criteria Bird/Wood (3)

Three or more of the following, or at least one of the following plus positive results on temporal artery
biopsy:
1. Bilateral shoulder pain and/or stiffness
2. Less than two weeks from onset of symptoms to maximal symptoms
3. ESR greater than 40 mm per hour
4. Morning stiffness lasting longer than one hour
5. Patient older than 65 years
6. Depression and/or weight loss
7. Bilateral upper arm tenderness

Criteria Jones and Hazleman (4)

All of the following:

85
 1. Shoulder and pelvic girdle muscle pain without weakness
2. Morning stiffness
3. Symptom duration of more than two months unless treated
4. ESR greater than 30 mm per hour or C-reactive protein level greater than 6 mg per L
5. No rheumatoid arthritis, inflammatory arthritis or malignant neoplasm
6. No objective signs of muscle disease
7. Prompt and dramatic response to systemic corticosteroid therapy

ESR = erythrocyte sedimentation rate.

riteria for the Classification of Systemic Sclerosis (Scleroderma)

1980 Criteria for the Classification of Systemic Sclerosis

The American College of Rheumatology (former American Rheumatism Association - ARA) has defined
criteria, that are 97 % sensitive and 98 % specific for systemic sclerosis (SSc) as follows:

Major criterion:

Proximal diffuse (truncal) sclerosis (skin tightness, thickening, non-pitting induration)

Minor criteria:

Sclerodactyly (only fingers and/or toes)

Digital pitting scars or loss of substance of the digital finger pads (pulp loss)
Bilateral basilar pulmonary fibrosis

The patient should fulfill the major criterion or two of the three minor criteria. Raynaud's phenomenon is
observed in 90-98 % of SSc patients.

Subsets of Systemic Sclerosis

Diffuse
Skin involvement Distal and proximal
extremities, face, trunk
Raynauds Onset within 1 year or at time of
phenomenon skin changes
Organ involvement Pulmonary (interstitial fibrosis);
renal (renovascular hypertensive
crisis); gastrointestinal; cardiac
Nail fold capillaries Dilatation and dropout
Antinuclear antibodies Anti-topoisomerase 1
Limited*
Distal to elbows, face
May precede skin disease by years
Gastrointestinal; pulmonary arterial
hypertension after 10-15 years of
disease in <10% of patients; biliary
cirrhosis
Dilatation without significant
dropout
Anticentromere

* Also referred to as CREST( calcinosis, Raynauds, esophageal dysmotility, sclerodactyly, telangiectasia).

ABCDCREST Criteria for the Classification of Systemic Sclerosis

86
 1. Autoantibodies: autoantibodies to centromere proteins (CENPs) detected by indirect
immunofluorescence; anti-Scl-70 (topoisomerase I) detected by double immunodiffusion; anti-
fibrillarin (U3-RNP) detected by immunoprecipitation
2. Bibasilar pulmonary fibrosis detected by chest radiograph: linear shadows or honey-comb
reticular appearance most expressed at the periphery of the lungs and at the bases
3. Contracture of the joints defined as permanent limitation of joint motion. The prayer sign is
detected when a patient opposed the palmar surfaces of both hands with extended wrists. The sign
is positive when the patient is unable to oppose the palms. This suggests joint or skin pathology, or
shortening of the forearm flexors
4. Dermal thickening can be defined by the modified Rodnan skin score, which employs clinical
palpation of the skin as described
5. Calcinosis cutis, most often located on the fingers, is intra and/or subcutaneous deposits of
hydroxyapatite that can ulcerate the skin; it can be detected by radiography, crystallographic or
chemical analysis
6. Raynauds phenomenon is a sudden pallor of an acral structure (e.g., fingers, whole hand, toes, tip
of nose, earlobe, or tongue). The involved area may subsequently develop cyanosis and, with re-
warming, become erythematous. Determination is by patients history or physicians observation
7. Esophageal distal hypomotility can be detected by cine/video barium esophagram, performed in
the upright and supine position. Reflux-esophagitis can be detected by
esophagogastroduodenoscopy in the forms of erosive esophagitis or Barrets esophagus
8. Sclerodactyly is symmetric thickening and tightening of the skin on the digits. Before
sclerodactyly develops there could be a phase of non-pitting digital edema of varying duration. It
is defined as non-pitting increase in soft tissue mass of the digits that extends beyond the normal
confines of the joint capsules
9. Teleangiectasias are visible macular dilatations of superficial cutaneous blood vessels that collapse
upon pressure and fill slowly when pressure is released. Common locations are the digits, face,
lips, tongue

A classification of definite SSc requires three or more criteria.

Revised International Classification Criteria for Sjgren's Syndrome (SS)

I. Ocular symptoms: a positive response to at least one of the following questions:

1. Have you had daily, persistent, troublesome dry eyes for more than 3 months?
2. Do you have a recurrent sensation of sand or gravel in the eyes?
3. Do you use tear substitutes more than 3 times a day?

II. Oral symptoms: a positive response to at least one of the following questions:
1. Have you had a daily feeling of dry mouth for more than 3 months?
2. Have you had recurrently or persistently swollen salivary glands as an adult?
3. Do you frequently drink liquids to aid in swallowing dry food?

III. Ocular signs-that is, objective evidence of ocular involvement defined as a positive result for at least
one of the following two tests:
1. Schirmer's I test, performed without anaesthesia (</=5 mm in 5 minutes)
2. Rose bengal score or other ocular dye score (>/=4 according to van Bijsterveld's scoring system)

IV. Histopathology: In minor salivary glands (obtained through normal-appearing mucosa) focal
lymphocytic sialoadenitis, evaluated by an expert histopathologist, with a focus score >/=1, defined as a
number of lymphocytic foci (which are adjacent to normal-appearing mucous acini and contain more than
50 lymphocytes) per 4 mm2 of glandular tissue

87
V. Salivary gland involvement: objective evidence of salivary gland involvement defined by a positive
result for at least one of the following diagnostic tests:
1. Unstimulated whole salivary flow (</=1.5 ml in 15 minutes)
2. Parotid sialography showing the presence of diffuse sialectasias (punctate, cavitary or destructive
pattern), without evidence of obstruction in the major ducts
3. Salivary scintigraphy showing delayed uptake, reduced concentration and/or delayed excretion of
tracer

VI. Autoantibodies: presence in the serum of the following autoantibodies:

1. Antibodies to Ro(SSA) or La(SSB) antigens, or both

Revised Rules for Classification

For primary SS
In patients without any potentially associated disease, primary SS may be defined as follows:
a. The presence of any 4 of the 6 items is indicative of primary SS, as long as either item IV
(Histopathology) or VI (Serology) is positive
b. The presence of any 3 of the 4 objective criteria items (that is, items III, IV, V, VI)
c. The classification tree procedure represents a valid alternative method for classification, although
it should be more properly used in clinical-epidemiological survey

For secondary SS
In patients with a potentially associated disease (for instance, another well defined connective tissue
disease), the presence of item I or item II plus any 2 from among items III, IV, and V may be considered as
indicative of secondary SS

Exclusion criteria:
Past head and neck radiation treatment
Hepatitis C infection
Acquired immunodeficiency disease (AIDS)
Pre-existing lymphoma
Sarcoidosis
Graft versus host disease
Use of anticholinergic drugs (since a time shorter than 4-fold the half life of the drug)

The European Spondyloarthropathy Study Group (ESSG) Classification for Spondyloarthropathy

(SpA)

According to the ESSG criteria, for a patient to be classified as having SpA, he or she has to satisfy one of
two entry criteria: Inflammatory spinal pain OR synovitis that is either asymmetric or predominantly in the
lower limbs.
Inflammatory back pain: Back pain is common among the general population. However,
"inflammatory" back pain is much less common. Back pain is considered inflammatory if four of
the following five criteria are found:
1. Onset of back discomfort before the age of 40 years
2. Insidious onset
3. Persistence for at least three months
4. Associated with morning stiffness
5. Improvement with exercise
Asymmetrical synovitis: Asymmetrical synovitis, predominantly of the lower limbs is manifested
by soft tissue swelling, warmth over a joint, joint effusion, and reductions in both active and
passive range of motion. As with inflammatory spinal pain, the symptoms are worse after a period
of rest.

88
Additional criteria: If a patient has one or both of the entry criteria listed above, he or she should then be
evaluated for the presence of one or more of the following features:
1. Positive family history
2. Psoriasis
3. Inflammatory bowel disease
4. Urethritis, cervicitis, or acute diarrhea within one month before arthritis
5. Buttock pain alternating between buttocks
6. Enthesopathy
7. Plain film radiographic evidence of sacroiliitis
Importantly, blood tests, including an assessment for the presence of HLA-B27, are not part of the ESSG
criteria; in addition, only the sacroiliac joints need to be evaluated radiographically.

Criteria for Diagnosis of Still's Disease

Yamaguchi criteria for classification of adult Still's disease

Presence of 5 or more criteria, of which at least 2 are Major (96% sensitivity; 92% specificity)

Major Criteria

Temperature of >39C for >1 wk

Leukocytosis >10,000/mm3 with >80% PMNs
Typical rash
Arthralgias >2 wk

Minor Criteria

Sore throat
Lymph node enlargement
Splenomegaly
Liver dysfunction (high AST/ALT)
Negative ANA, RF

Cush criteria for classification of adult Still's disease

Requires all of the following:

Fever > 39 degrees

Arthralgia or arthritis
Rheumatoid factor < 1:80
ANA < 1:100

In addition to any two of the following:

WBC count > 15,000

Stills rash
Pleuritis or Pericarditis
Hepatomegaly, Splenomegaly, or Lymphadenopathy

Abbreviations: ALT, alanine transaminase; ANA, antinuclear antibody; AST, aspartate transminase; PMN,
polymorphonuclear leukocyte; RF, rheumatoid factor; WBC, white blood cells.

89
1990 Criteria of American College of Rheumatology for the Classification of Takayasu Arteritis

Criteria Definition
Age at disease onset in year Development of symptoms or findings related to Takayasu arteritis at age <40
years.
Claudication of extremities Development and worsening of fatigue and discomfort in muscles of one or
more extremity while in use, especially the upper extremities.
Decreased brachial artery Decreased pulsation of one or both brachial arteries
pulse
BP difference >10mmHg Difference of >10mmHg in systolic blood pressure between arms
Bruit over subclavian Bruit audible on auscultation over one or both subclavian arteries or abdominal
arteries or aorta aorta
Arteriogram abnormality Arteriographic narrowing or occlusion of the entire aorta, its primary branches,
or large arteries in the proximal uppper or lower extremities, not due
arteriosclerosis, fibro-muscular dysplasia, or similar causes: changes usually
focal or segmental

For purposes of classification, a patient shall be said to have Takayasu's arteritis if at least three of these six
criteria are present. The presence of any three or more criteria yields a sensitivity of 90.5% and a specificity
of 97.8%. BP = blood pressure (systolic) difference between arms

Ishikawa's Criteria for Takayasu's Arteritis (Modified According to Sharma et al.)

Three major criteria:

1. Left mid subclavian artery lesion: The most severe stenosis or occlusion present in the mid portion
from the point 1 cm proximal to the vertebral artery orifice up to that 3 cm distal to the orifice
determined by angiography
2. Right mid subclavian artery lesion: The most severe stenosis or occlusion present in the mid
portion from the right vertebral artery orifice to the point 3 cm distal to orifice determined by
angiography
3. Characteristic signs and symptoms of at least one month duration: These include limb
claudication, pulselessness or pulse differences in limbs, an unobtainable or significant blood
pressure difference (> 10 mmHg systolic blood pressure difference in limb), fever, neck pain,
transient amaurosis, blurred vision, syncope, dyspnea or palpitations.

Ten minor criteria

1. High ESR: Unexplained persistent high erythrocyte sedimentation rate (ESR) >20 mm/h
(Westergren) at diagnosis or presence of the evidence in patients history
2. Carotid artery tenderness: Unilateral or bilateral tenderness of common arteries on palpation. Neck
muscle tender ness is unacceptable
3. Hypertension: Persistent blood pressure > 140/90 mmHg brachial or > 160/90 mmHg popliteal
4. Aortic regurgitation or Anuloaortic ectasia: Aortic regurgitation by auscultation or Doppler
echocardiography or angiography; or Anuloaortic ectasia by angiography or two-dimensional
echocardiography
5. Pulmonary artery lesion: Lobar or segmental arterial occlusion or equivalent determined by
angiography or perfusion scintigraphy, or presence of stenosis, aneurysm, luminal irregularity or
any combination in pulmonary trunk or in unilateral or bilateral pulmonary arteries determined by
angiography.
6. Left mid common carotid lesion: Presence of the most severe stenosis or occlusion in the mid
portion of 5 cm in length from the point 2 cm distal to its orifice determined by angiography.

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 7. Distal brachiocephalic trunk lesion:. Presence of the most stenosis or occlusion in the distal third
determined by angiography
8. Descending thoracic aorta lesion: Narrowing, dilatation or aneurysm, luminal irregularity or any
combination determined by angiography: tortuosity alone is unacceptable.
9. Abdominal aorta lesion: Narrowing, dilatation or aneurysm, luminal irregularity or aneurysm
combination.
10. Coronary artery lesion: Documented on angiography below the age of 30 years in the absence of
risk factors like hyperlipidemia or diabetes mellitus

Presence of two major or one major and two minor criteria or four minor criteria suggests a high
probability of Takayasu's arteritis

ACR Criteria for the Classification of Hypersensitivity Vasculitis

Three of the following five criteria were required to meet American College of Rheumatology (ACR)
classification criteria for hypersensitivity vasculitis:

1. Age at disease onset older than 16 years.

2. Medication at disease onset as a precipitating factor.
3. Palpable purpura.
4. Maculopapular rash.
5. Biopsy specimen showing granulocytes around an arteriole and venule.

These criteria have a reported sensitivity of 71% and a reported specificity of 83.9% for the classification
of hypersensitivity vasculitis compared with other vasculitides.

ROME II Diagnostic Criteria for Functional Disorders of the Anus and Rectum

The diagnosis of a Functional Disorder of the Anus and Rectum always presumes the absence of a
structural or biochemical explanation for the symptoms.

F1. Functional Fecal Incontinence

Recurrent uncontrolled passage of fecal material for at least one month, in an individual with a
developmental age of at least 4 years, associated with:

1. Fecal impaction; or
2. Diarrhea; or
3. Nonstructural anal sphincter dysfunction.

F2. Functional Anorectal Pain

F2a. Levator Ani Syndrome

At least 12 weeks, which need not be consecutive, in the preceding 12 months of:

1. Chronic or recurrent rectal pain or aching;

2. Episodes last 20 minutes or longer; and
3. Other causes of rectal pain such as ischemia, inflammatory bowel disease, cryptitis, intramuscular
abscess, fissure, hemorrhoids, prostatitis, and solitary rectal ulcer have been excluded.

F2b. Proctalgia Fugax

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 1. Recurrent episodes of pain localized to the anus or lower rectum;
2. Episodes last from seconds to minutes; and
3. There is no anorectal pain between episodes.

F3. Pelvic Floor Dyssynergia

1. The patient must satisfy diagnostic criteria for functional constipation in Diagnostic Criteria C3;
2. There must be manometric, EMG, or radiologic evidence for inappropriate contraction or failure
to relax the pelvic floor muscles during repeated at-tempts to defecate;
3. There must be evidence of adequate propulsive forces during attempts to defecate, and
4. There must be evidence of incomplete evacuation.

ROME II Diagnostic Criteria for Functional Disorders of the Biliary Tract and the Pancreas

The diagnosis of a Functional Disorder of the Biliary Tract and Pancreas always pre-sumes the absence of a
structural or biochemical explanation for the symptoms.

E1. Gallbladder Dysfunction

Episodes of severe steady pain located in the epigastrium and right upper quadrant, and all of the following:

1. Symptom episodes last 30 minutes or more, with pain-free intervals;

2. Symptoms have occurred on one or more occasions in the previous 12 months;
3. The pain is steady and interrupts daily activities or requires consultation with a physician;
4. There is no evidence of structural abnormalities to explain the symptoms; and
5. There is abnormal gallbladder functioning with regard to emptying.

E2. Sphincter of Oddi Dysfunction

Episodes of severe steady pain located in the epigastrium and right upper quadrant, and all of the following:

1. Symptom episodes last 30 minutes or more, with pain-free intervals;

2. Symptoms have occurred on one or more occasions in the previous 12 months;
3. The pain is steady and interrupts daily activities or requires consultation with a physician; and

ROME II Diagnostic Criteria for Functional Bowel Disorders

The diagnosis of a Functional Bowel Disorder always presumes the absence of a structural or biochemical
explanation for the symptoms.

C1. Irritable Bowel Syndrome

At least 12 weeks, which need not be consecutive, in the preceding 12 months of abdominal discomfort or
pain that has two out of three features:

1. Relieved with defecation; and/or

2. Onset associated with a change in frequency of stool; and/or
3. Onset associated with a change in form (appearance) of stool.

Symptoms that Cumulatively Support the Diagnosis of Irritable Bowel Syndrome

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 Abnormal stool frequency (for research purposes abnormal may be defined as greater than 3
bowel movements per day and less than 3 bowel movements per week);
Abnormal stool form (lumpy/hard or loose/watery stool);
Abnormal stool passage (straining, urgency, or feeling of incomplete evacuation);
Passage of mucus;
Bloating or feeling of abdominal distension.

C2. Functional Abdominal Bloating

At least 12 weeks, which need not be consecutive, in the preceding 12 months of:

1. Feeling of abdominal fullness, bloating, or visible distension; and

2. Insufficient criteria for a diagnosis of functional dyspepsia, irritable bowel syndrome, or other
functional disorder.

C3. Functional Constipation

At least 12 weeks, which need not be consecutive, in the preceding 12 months of two or more of:

1. Straining >1/4 of defecations;

2. Lumpy or hard stools >1/4 of defecations;
3. Sensation of incomplete evacuation >1/4 of defecations;
4. Sensation of anorectal obstruction/blockage >1/4 of defecations;
5. Manual maneuvers to facilitate >1/4 of defecations (e.g., digital evacuation, support of the pelvic
floor); and/or
6. < 3 defecations per week.

Loose stools are not present, and there are insufficient criteria for IBS.

C4. Functional Diarrhea

At least 12 weeks, which need not be consecutive, in the preceding 12 months of:

1. Loose (mushy) or watery stools

2. Present >3/4 of the time; and
3. No abdominal pain.

C5. Unspecified Functional Bowel Disorder

Bowel symptoms in the absence of organic disease that do not fit into the previously defined categories of
functional bowel disorders.

ROME II Diagnostic Criteria for Childhood Functional Gastrointestinal Disorders

The diagnosis of a Childhood Functional Gastrointestinal Disorder always presumes the absence of a
structural or biochemical explanation for the symptoms.

G1.Vomiting

G1a. Infant Regurgitation

1. Regurgitation 2 or more times per day for 3 or more weeks;

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 2. There is no retching, hematemesis, aspiration, apnea, failure-to-thrive, or abnormal posturing;
3. The infant must be 1 to 12 months of age and otherwise healthy; and
4. There is no evidence of metabolic, gastrointestinal, or central nervous system disease to explain
the symptom.

G1b. Infant Rumination Syndrome

1. At least 3 months of stereotypical behavior beginning with repetitive contractions of the abdominal
muscles, diaphragm, and tongue, and culminating in regurgitation of gastric contents into the mouth, which
is either expectorated or rechewed and reswallowed, and 3 or more of the following:

a. Onset between 3 and 8 months of age;

b. Does not respond to management for gastroesophageal reflux disease, anticholinergic drugs, hand
restraints, formula changes, and gavage or gastrostomy feedings;
c. Unaccompanied by signs of nausea or distress; and/or
d. Does not occur during sleep and when the infant is interacting with in-dividuals in the
environment.

G1c. Cyclic Vomiting Syndrome

1. A history of 3 or more periods of intense, acute nausea, and unremitting vomiting lasting hours to
days, with intervening symptom-free intervals lasting weeks to months.
2. There is no metabolic, gastrointestinal, or central nervous system structural or biochemical
disease.

G2. Abdominal Pain

G2a. Functional Dyspepsia

In children mature enough to provide an accurate pain history, at least 12 weeks, which need not be
consecutive, in the preceding 12 months of:

1. Persistent or recurrent pain or discomfort centered in the upper abdomen (above the umbilicus);
2. No evidence of organic disease (including at upper endoscopy) that is likely to explain the
symptoms; and
3. No evidence that dyspepsia is exclusively relieved by defecation or associated with onset of a
change in stool frequency or stool form (i.e., not irritable bowel).

G2a1. Ulcer-like Dyspepsia: Pain centered in the upper abdomen is the predominant (most bothersome)
symptom.

G2a2. Dysmotility-like Dyspepsia: An unpleasant or troublesome nonpainful sensation (discomfort)

centered in the upper abdomen is the predominant symptom; this sensation may be characterized by early
satiety, upper abdominal fullness, bloating, or nausea.

G2a3. Unspecified (Nonspecific) Dyspepsia: Symptomatic patients whose symptoms do not fulfill the
criteria for either ulcer-like or dysmotility-like dyspepsia.

G2b. Irritable Bowel Syndrome

In children old enough to provide an accurate pain history, at least 12 weeks, which need not be
consecutive, of continuous or recurrent symptoms during the preceding 12 months of:

94
1. Abdominal discomfort or pain that has two out of three features:

a. Relieved with defecation; and/or

b. Onset associated with a change in frequency of stool; and/or
c. Onset associated with a change in form (appearance) of stool.

2. There are no structural or metabolic abnormalities to explain the symptoms.

Symptoms that Cumulatively Support the Diagnosis of Irritable Bowel Syndrome

Abnormal stool frequency (for research purposes abnormal may be defined as greater than 3
bowel movements per day and less than 3 bowel movements per week);
Abnormal stool form (lumpy/hard or loose/watery stool);
Abnormal stool passage (straining, urgency, or feeling of incomplete evacuation);
Passage of mucus;
Bloating or feeling of abdominal distension.

G2c. Functional Abdominal Pain

At least 12 weeks of:

1. Continuous or nearly continuous abdominal pain in a school-aged child or adolescent; and

2. No or only occasional relationship of pain with physiological events (e.g., eating, menses,
defecation); and
3. Some loss of daily functioning; and
4. The pain is not feigned (e.g., malingering); and
5. Insufficient criteria for other functional gastrointestinal disorders that would explain the
abdominal pain.

G2d. Abdominal Migraine

1. In the preceding 12 months, 3 or more paroxysmal episodes of intense, acute midline abdominal pain
lasting 2 hours to several days, with intervening symptom-free intervals of weeks to months; and

2. Evidence of metabolic, gastrointestinal, and central nervous system structural or biochemical diseases is
absent; and

3. Two of the following features:

a. Headache during episodes;

b. Photophobia during episodes;
c. Family history of migraine;
d. Headache confined to one side only; and
e. An aura or warning period consisting of either visual symptoms (e.g., blurred or restricted vision)
or sensory symptoms (e.g., numbness or tingling), or motor symptoms (e.g., slurred speech,
inability to speak, paralysis).

G2e. Aerophagia

At least 12 weeks, which need not be consecutive, in the preceding 12 months of two or more of the
following signs and symptoms:

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 1. Air swallowing;
2. Abdominal distension due to intraluminal air; and
3. Repetitive belching and/or increased flatus.

G3. Functional Diarrhea (also called Toddlers Diarrhea, chronic nonspecific diarrhea, irritable
colon of childhood)

For more than 4 weeks, daily painless, recurrent passage of 3 or more large, unformed stools, in addition to
all these characteristics:

1. Onset of symptoms begins between 6 and 36 months of age;

2. Passage of stools occurs during waking hours; and
3. There is no failure-to-thrive if caloric intake is adequate.

G4. Disorders of Defecation

G4a. Infant dyschezia

At least 10 minutes of straining and crying before successful passage of soft stools in an otherwise healthy
infant less than 6 months of age.

G4b. Functional Constipation

In infants and children, at least 2 weeks of:

1. Scybalous, pebble-like, hard stools for a majority of stools; or

2. Firm stools 2 or less times/week; and
3. There is no evidence of structural, endocrine, or metabolic disease.

G4c. Functional Fecal Retention

From infancy to 16 years old, a history of at least 12 weeks of:

1. Passage of large diameter stools at intervals < 2 times per week; and
2. Retentive posturing, avoiding defecation by purposefully contracting the pelvic floor. As pelvic
floor muscles fatigue, the child uses gluteal muscles, squeezing the buttocks together.

Accompanying symptoms may include fecal soiling, irritability, abdominal cramps, decreased appetite
and/or early satiety. The accompanying symptoms disappear immediately following passage of a large
stool.

G4d. Functional Non-retentive Fecal Soiling

Once a week or more for the preceding 12 weeks, in a child older than 4 years, a history of:

1. Defecation into places and at times inappropriate to the social context;

2. In the absence of structural or inflammatory disease; and
3. In the absence of signs of fecal retention (listed in G4c above).

ROME II Diagnostic Criteria for Functional Esophageal Disorders

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The diagnosis of a Functional Esophageal Disorder always presumes the absence of a structural or
biochemical explanation for the symptoms.

A1. Globus

At least 12 weeks, which need not be consecutive, in the preceding 12 months of:

1. The persistent or intermittent sensation of a lump or foreign body in the throat;

2. Occurrence of the sensation between meals;
3. Absence of dysphagia and odynophagia; and
4. Absence of pathologic gastroesophageal reflux, achalasia, or other motility disorder with a
recognized pathologic basis (e.g., scleroderma of the esophagus).

A2. Rumination Syndrome

At least 12 weeks, which need not be consecutive, in the preceding 12 months of:

1. Persistent or recurrent regurgitation of recently ingested food into the mouth with subsequent
remastication and swallowing or spitting it out;
2. Absence of nausea and vomiting;
3. Cessation of the process when the regurgitated material becomes acidic; and
4. Absence of pathologic gastroesophageal reflux, achalasia, or other motility disorder with a
recognized pathologic basis as the primary disorder.

A3. Functional Chest Pain of Presumed Esophageal Origin

At least 12 weeks, which need not be consecutive, within the preceding 12 months of:

1. Midline chest pain or discomfort that is not of burning quality; and

2. Absence of pathologic gastroesophageal reflux, achalasia, or other motility disorder with a
recognized pathologic basis.

A4. Functional Heartburn

At least 12 weeks, which need not be consecutive, in the preceding 12 months of:

1. Burning retrosternal discomfort or pain; and

2. Absence of pathologic gastroesophageal reflux, achalasia, or other motility disorder with a
recognized pathologic basis.

A5. Functional Dysphagia

At least 12 weeks, which need not be consecutive, in the preceding 12 months of:

1. Sense of solid and/or liquid foods sticking, lodging, or passing abnormally through the esophagus;
and
2. Absence of pathologic gastroesophageal reflux, achalasia, or other motility disorder with a
recognized pathologic basis.

A6. Unspecified Functional Esophageal Disorder

At least 12 weeks, which need not be consecutive, in the preceding 12 months of:

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 1. Unexplained symptoms attributed to the esophagus that do not fit into the previously described
categories; and
2. Absence of pathologic gastroesophageal reflux, achalasia, or other motility disorder with a
recognized pathologic basis.

ROME II Diagnostic Criteria for Functional Gastroduodenal Disorders

The diagnosis of a Functional Gastroduodenal Disorder always presumes the absence of a structural or
biochemical explanation for the symptoms.

B1. Functional Dyspepsia

At least 12 weeks, which need not be consecutive, in the preceding 12 months of:

1. Persistent or recurrent symptoms (pain or discomfort centered in the upper abdomen);

2. No evidence of organic disease (including at upper endoscopy) that is likely to explain the
symptoms; and
3. No evidence that dyspepsia is exclusively relieved by defecation or associated with the onset of a
change in stool frequency or stool form (i.e., not irritable bowel).

B1a. Ulcer-like Dyspepsia

Pain centered in the upper abdomen is the predominant (most bother-some) symptom.

B1b. Dysmotility-like Dyspepsia

An unpleasant or troublesome nonpainful sensation (discomfort) centered in the upper abdomen is the
predominant symptom; this sensation may be characterized by or associated with upper abdominal fullness,
early satiety, bloating, or nausea.

B1c. Unspecified (Nonspecific) Dyspepsia

Symptomatic patients whose symptoms do not fulfill the criteria for ulcer-like or dysmotility-like
dyspepsia.

B2. Aerophagia

At least 12 weeks, which need not be consecutive, in the preceding 12 months of:

1. Air swallowing that is objectively observed; and

2. Troublesome repetitive belching.

B3. Functional Vomiting

At least 12 weeks, which need not be consecutive, in the preceding 12 months of:

1. Frequent episodes of vomiting, occurring on at least three separate days in a week over three
months;
2. Absence of criteria for an eating disorder, rumination, or major psychiatric disease according to
DSM-IV;
3. Absence of self-induced and medication-induced vomiting; and

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 4. Absence of abnormalities in the gut or central nervous system, and metabolic diseases to explain
the recurrent vomiting.

DSM-IV Diagnostic Criteria for Panic Disorder With or Without Agoraphobia

A. Both (1) and (2):

(1) recurrent unexpected Panic Attacks

(2) at least one of the attacks has been followed by 1 month (or more) of one (or
more) of the following:
a. persistent concern about having additional attacks
b. worry about the implications of the attack or its consequences (e.g.,
losing control, having a heart attack, "going crazy")
c. a significant change in behavior related to the attacks

B. Presence or Absence of Agoraphobia

C. The Panic Attacks are not due to the direct physiological effects of a substance
(e.g., a drug of abuse, a medication) or a general medical condition (e.g.,
hyperthyroidism).

D. The Panic Attacks not better accounted for by another mental disorder, such as
Social Phobia (e.g., occurring on exposure to feared social situations), Specific
Phobia (e.g., on exposure to a specific phobic situation), Obsessive-Compulsive
Disorder (e.g., on exposure to dirt in someone with an obsession about
contamination), Posttraumatic Stress Disorder (e.g., in response to stimuli
associated with a severe stressor), or Separation Anxiety Disorder (e.g., in response
to being away from home or close relatives).

Diagnostic Criteria in Polycystic Ovary Syndrome (PCOS)

Revised diagnostic criteria of PCOS

1999 criteria (both 1 and 2)
1. Chronic anovulation
2. Clinical and/or biochemical signs of hyperandrogenism, and exclusion of other aetiologies

Revised 2003 criteria (2 out of 3)

1. Oligo- and/or anovulation
2. Clinical and/or biochemical signs of hyperandrogenism
3. Polycystic ovaries
and exclusion of other aetiologies (congenital adrenal hyperplasias, androgen-secreting tumours, Cushings
syndrome)

Other Proposed Diagnostic Criteria in Polycystic Ovary Syndrome

1. Inappropriate gonadotropin secretion
a) Elevated LH-to-FSH ratio
b) Abnormal response to GnRH agonist testing
2. Hyperandrogenism
a) Hirsutism, androgenic alopecia, acne
b) Hyperandrogenemia
I. Total testosterone

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 II. Free testosterone (free androgen index, etc.)
3. Ovarian appearance
a) Polycystic-appearing ovaries
b) Increased (stromal) size
4. Insulin resistance
a) Acanthosis nigricans
b) Fasting measures of insulin/glucose
c) Oral glucose tolerance test
d) Dynamic tests of insulin sensitivity
I. Euglycemic clamp
II. Frequently sampled intravenous glucose tolerance test
5. Chronic anovulation
a) Self-reported history
b) Tests of ovulatory function
I. Basal body temperature charting
II. Urinary LH testing
III. Serum progesterone measurement
IV. Endometrial biopsy

FSH, follicle-stimulating hormone; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone.

Diagnostic Criteria for Cystic Fibrosis (CF)

One or more typical phenotypic features of CF:

Chronic sinopulmonary disease
Characteristic gastrointestinal and nutritional abnormalities
Salt loss syndromes
Obstructive azoospermia
or

A history of cystic fibrosis in a sibling

or

A positive newborn screening test

PLUS

An elevated sweat chloride concentration (greater than 60 meq/L) on two or more occasions

or

Identification of mutations in each cystic fibrosis transmembrane conductance regulator (CFTR) protein
gene known to cause CF

or

In vivo demonstration of characteristic abnormalities in ion transport across the nasal epithelium

Clinical Manifestations of Cystic Fibrosis

Respiratory

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 Bronchiolitis / asthma
Psudomonas aeruginosa colonization of the respiratory tract
Staphylococcal pneumonia
Nasal polyposis
Sinusitis
Gastrointestinal
Meconium ileus
Rectal prolapse
Recurrent abdominal pain and/or right lower quadrant mass
Hypoproteinemic edema
Prolonged neonatal jaundice
Biliary cirrhosis with portal hypertension
Vitamin deficiency states (A, D, E, K)
Acrodermatitis enterophatica-like eruption with fatty acid and zinc deficiency
Recurrent pancreatitis
Volvulus in fetal life
Genitourinary
Congenital bilateral absence of the vas deferens (CBAVD)
Male infertility
Female infertility
Other
Hypochloremic, hyponatremic alkalosis
Mother of child with cystic fibrosis
Pseudotumor cerebri

Diagnostic Criteria for Common Variable Immunodeficiency (CVI)

Probable

Male or female patient who has a marked decrease (at least 2 SD below the mean for age) in serum IgG and
IgA and fulfills all of the following criteria:

1. Onset of immunodeficiency at greater than 2 years of age.

2. Absent isohemagglutinins and/or poor response to vaccines.
3. Defined causes of hypogammaglobulinemia have been excluded.

Possible

Male or female patient who has a marked decrease (at least 2 SD below the mean for age) in one of the
major isotypes (IgM, IgG, and IgA) and fulfills all of the following criteria:

1. Onset of immunodeficiency at greater than 2 years of age.

2. Absent isohemagglutinins and/or poor response to vaccines.
3. Defined causes of hypogammaglobulinemia have been excluded.

Differential Diagnosis of Hypogammaglobulinemia

Drug induced

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 Antimalarial agents
Captopril
Carbamazepine
Glucocorticoids
Fenclofenac
Gold salts
Penicillamine
Phenytoin
Sulfasalazine
Genetic disorders
Ataxia telangiectasia
Autosomal forms of Severe Combined Immunodeficiency (SCID)
Hyper IgM immunodeficiency
Transcobalamin II deficiency and hypogammaglobulinemia
X-linked agammaglobulinemia
X-linked lymphoproliferative disorder (EBV associated)
X-linked SCID
Some metabolic disorders
Chromosomal anomalies
Chromosome 18q2 syndrome
Monosomy 22
Trisomy 8
Trisomy 21
Infectious diseases
HIV
Congenital rubella
Congenital infection with CMV
Congenital infection with Toxoplasma gondii
EpsteinBarr virus
Malignancy
Chronic lymphocytic leukemia
Immunodeficiency with thymoma
Non-Hodgkin lymphoma
B cell malignancy
Systemic disorders
Immunodeficiency caused by hypercatabolism of immunoglobulin
Immunodeficiency caused by excessive loss of immunoglobulins (nephrosis, severe burns,
lymphangiectasia, severe diarrhea)

Modified Bells Staging Criteria for Necrotizing Enterocolitis (NEC)

Stage Systemic signs Abdominal signs Radiographic signs Treatment

IA Temperature Gastric retention, Normal or intestinal NPO, antibiotics x
Suspected instability, apnea, abdominal distention, dilation, mild ileus 3 days
bradycardia, lethargy emesis, heme-positive
stool
IB Same as above Grossly bloody stool Same as above Same as IA
Suspected
IIA Same as above Same as above, plus Intestinal dilation, ileus, NPO, antibiotics x
Definite, absent bowel sounds pneumatosis intestinalis 7 to 10 days
mildly ill with or without
abdominal tenderness
IIB Same as above, plus Same as above, plus Same as IIA, plus NPO, antibiotics x

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Definite, mild metabolic absent bowel sounds, ascites 14 days
moderately acidosis and definite tenderness,
ill thrombocytopenia with or without
abdominal cellulitis or
right lower quadrant
mass
IIIA Same as IIB, plus Same as above, plus Same as IIA, plus NPO, antibiotics x
Advanced, hypotension, signs of peritonitis, ascites 14 days, fluid
severely ill, bradycardia, severe marked tenderness, resuscitation,
intact bowel apnea, combined and abdominal inotropic support,
respiratory and distention ventilator therapy,
metabolic acidosis, paracentesis
DIC, and neutropenia
IIIB Same as IIIA Same as IIIA Same as above, plus Same as IIA, plus
Advanced, pneumoperitoneum surgery
severely ill,
perforated
bowel
DIC: disseminated intravascular coagulation
NPO: nil per os or nothing by mouth

Rochester Criteria for Identifying Febrile Infants at Low Risk for Serious Bacterial Infection

1- Infant appears generally well

2- Infant has been previously healthy:
Born at term (>/=37 weeks of gestation)
No perinatal antimicrobial therapy
No treatment for unexplained hyperbilirubinemia
No previous antimicrobial therapy
No previous hospitalization
No chronic or underlying illness
Not hospitalized longer than mother
3- Infant has no evidence of skin, soft tissue, bone, joint or ear infection
4- Infant has these laboratory values:
White blood cell count of 5,000 to 15,000 per mm3 (5 to 15 x 109 per L)
Absolute band cell count of </=1,500 per mm3 (</=1.5 x 109 per L)
Ten or fewer white blood cells per high-power field on microscopic examination of urine
Five or fewer white blood cells per high-power field on microscopic examination of stool in infant
with diarrhea

Diagnostic Criteria for Acute Pharyngitis

Adults

Clinical suspicion of streptococcal pharyngitis (e.g., fever, tonsillar swelling, exudate, enlarged/tender
anterior cervical lymph nodes, absence of cough or coryza) with

History of rheumatic fever or

Documented household exposure or
Positive rapid strep screen

Children

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Clinical suspicion of streptococcal pharyngitis (e.g., tonsillar swelling, exudate, enlarged/tender anterior
cervical lymph nodes, absence of coryza) with

History of rheumatic fever or

Documented household exposure or
Positive rapid strep screen or
Positive throat culture (for those with negative rapid strep screen)

Streptococcal Pharyngitis Score (Sore Throat Score)

Symptoms Points
Fever (subjective or measured in office) 1
Absence of cough 1
Tender anterior cervical adenopathy 1
Tonsillar swelling or exudates1 1
Age
Younger than 15 years +1
15 to 45 years 0
Older than 45 years -1

SCORING:
0 or -1 points: streptococcal infection ruled out (2 percent);
1 to 3 points: order rapid test and treat accordingly;
4 to 5 points: probable streptococcal infection (52 percent), consider empiric antibiotics.

Diagnostic Criteria of Paraneoplastic Neurological Disorder (PND) of the CNS

Definite PND

1. Classic syndrome with cancer diagnosed within 5 years of neurological symptom development
2. Nonclassic syndrome that resolves or significantly improves after cancer treatment
3. Nonclassic syndrome with cancer diagnosed within 5 years of neurological symptom development
and positive antineuronal antibodies
4. Neurological syndrome (classic or not) without cancer and with well-characterized antineuronal
antibodies

Possible PND

1. Classic syndrome with high risk of cancer, without antineuronal antibodies

2. Neurological syndrome (classic or not) without cancer and with partially characterized
antineuronal antibodies
3. Nonclassic syndrome with cancer diagnosed within 2 years of neurological symptom
development, without antineuronal antibodies

PND, paraneoplastic neurological disorder; CNS, central nervous system

Diagnostic Criteria for Relapsing Polychondritis

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Three or more clinical signs must be present:

1. Recurrent chondritis both auricles

2. Non-erosive inflammatory polyarthritis
3. Nasal chondritis
4. Ocular inflammation
5. Respiratory tract chondritis
6. Cochlear and, or, vestibular dysfunction

OR 1 or more signs with histologic confirmation

OR Chondritis in 2 or more separate sites AND response to steroids or immunosuppression

Differential diagnosis for these individual symptoms and signs includes most of the autoimmune disorders
and other infectious and non-infectious granulomatous disorders including Wegener's granulomatosis,
polyarteritis nodosa (PAN), Takayasu's arteritis, giant cell arteritis (GCA), rheumatoid arthritis, Reiter's
syndrome, rheumatic fever, polymorphic reticulosis, syphilis, tuberculosis, histoplasmosis, leprosy,
sarcoidosis, and malignancy.

GINA Classification of Asthma Severity

Symptoms/Day Symptoms/Night PEF or FEV1 PEF variability

STEP 1 < 1 time a week </= 2 times a month >/= 80% < 20%
Intermittent
Asymptomatic and
normal PEF between
attacks
STEP 2 > 1 time a week but < 1 > 2 times a month >/= 80% 20-30%
Mild time a day
Persistent
Attacks may affect
activity
STEP 3 Daily > 1 time a week 60%-80% > 30%
Moderate
Persistent Attacks affect activity
STEP 4 Continuous Frequent </= 60% > 30%
Severe
Persistent Limited physical activity

PEF, Peak Expiratory Flow; FEV1, Forced Expiratory Volume in the first second.
The presence of one of the features of severity is sufficient to place a patient in that category.
Patients at any level of severity-even intermittent asthma-can have severe attacks.

GOLD Staging System for Chronic Obstructive Lung Disease (COPD) Severity

Definition
COPD is a disease state characterized by airflow limitation that is not fully reversible. The airflow
limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs
to noxious particles or gases.

GOLD Staging System for COPD Severity

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Stage Description Findings (based on postbronchodilator FEV1)
0 At risk Risk factors and chronic symptoms but normal spirometry
I Mild FEV1/FVC ratio less than 70 percent
FEV1 at least 80 percent of predicted value
May have symptoms
II Moderate FEV1/FVC ratio less than 70 percent
FEV1 50 percent to less than 80 percent of predicted value
May have chronic symptoms
III Severe FEV1/FVC ratio less than 70 percent
FEV1 30 percent to less than 50 percent of predicted value
May have chronic symptoms
IV Very severe FEV1/FVC ratio less than 70 percent
FEV1 less than 30 percent of predicted value
or
FEV1 less than 50 percent of predicted value plus severe chronic
symptoms

GOLD = Global Initiative for Chronic Obstructive Lung Disease; COPD = chronic obstructive pulmonary
disease; FEV1 = forced expiratory volume in one second; FVC = forced vital capacity.

Diagnostic Criteria for Sepsis

Infection,a documented or suspected, and some of the following:b

General variables
Fever (core temperature >38.3C)
Hypothermia (core temperature <36C)
Heart rate >90 /min or >2 SD above the normal value for age
Tachypnea
Altered mental status
Significant edema or positive fluid balance (>20 mL/kg over 24 hrs)
Hyperglycemia (plasma glucose >120 mg/dL or 7.7 mmol/L) in the absence of diabetes
Inflammatory variables
Leukocytosis (WBC count >12,000 /mm3)
Leukopenia (WBC count <4000 /mm3)
Normal WBC count with >10% immature forms
Plasma C-reactive protein >2 SD above the normal value
Plasma procalcitonin >2 SD above the normal value
Hemodynamic variables
Arterial hypotensionb (SBP <90 mm Hg, MAP <70, or an SBP decrease >40 mm Hg in adults or <2
SD below normal for age)
SvO2 >70%b
Cardiac index (CI) >3.5 L.min-1.M-23
Organ dysfunction variables
Arterial hypoxemia (PaO2/FIO2 <300)
Acute oliguria (urine output <0.5 mL.kg-1.hr-1 or 45 mmol/L for at least 2 hrs)
Creatinine increase >0.5 mg/dL
Coagulation abnormalities (INR >1.5 or aPTT >60 secs)
Ileus (absent bowel sounds)
Thrombocytopenia (platelet count <100,000 /mm3)

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 Hyperbilirubinemia (plasma total bilirubin >4 mg/dL or 70 mmol/L)
Tissue perfusion variables
Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

WBC, white blood cell; SBP, systolic blood pressure; MAP, mean arterial blood pressure; SvO2, mixed
venous oxygen saturation; INR, international normalized ratio; aPTT, activated partial thromboplastin time.
a
Infection defined as a pathologic process induced by a microorganism;
b
SvO2 sat >70% is normal in children (normally, 7580%), and CI 3.55.5 is normal in children; therefore,
NEITHER should be used as signs of sepsis in newborns or children;
c
diagnostic criteria for sepsis in the pediatric population are signs and symptoms of inflammation plus
infection with hyper- or hypothermia (rectal temperature >38.5 or < 35C), tachycardia (may be absent in
hypothermic patients), and at least one of the following indications of altered organ function: altered mental
status, hypoxemia, increased serum lactate level, or bounding pulses.

Definitions for the Terms Bacteremia, Sepsis, Severe Sepsis, Septic Shock, and Other Related
Disorders

A 1992 American College of Chest Physicians/Society of Critical Care Medicine consensus panel defined
the following terms which are relevant to the discussion of septic shock:

Infection: Infection is a microbial phenomenon characterized by an inflammatory response to the presence

of microorganisms or the invasion of normally sterile host tissue by those organisms.

Bacteremia: Bacteremia refers to the presence of viable bacteria in the blood.

Systemic inflammatory response syndrome: Systemic inflammatory response syndrome (SIRS) is a

widespread inflammatory response to a variety of severe clinical insults. This syndrome is clinically
recognized by the presence of two or more of the following:

Temperature >38C or <36C

Heart rate >90 beats/min
Respiratory rate >20 breaths/min or PaCO2 <32 mmHg
WBC >12,000 cells/mm3, <4000 cells/mm3, or >10 percent immature (band) forms

Sepsis: Sepsis is the systemic response to infection. Thus, in sepsis, the clinical signs describing SIRS are
present together with definitive evidence of infection.

Severe sepsis: Sepsis is considered severe when it is associated with organ dysfunction, hypoperfusion, or
hypotension. The manifestations of hypoperfusion may include, but are not limited to, lactic acidosis,
oliguria, or an acute alteration in mental status.

Septic shock: Septic shock is sepsis with hypotension despite adequate fluid resuscitation. It includes
perfusion abnormalities such as lactic acidosis, oliguria, or an acute alteration in mental status. Patients
receiving inotropic or vasopressor agents may not be hypotensive at the time that perfusion abnormalities
are measured.

Hypotension: Hypotension is defined as a systolic BP of <90 mmHg or a reduction of >40 mmHg from
baseline, in the absence of other causes for the fall in blood pressure.

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Multiple organ dysfunction syndrome: Multiple organ dysfunction syndrome (MODS) refers to the
presence of altered organ function in an acutely ill patient such that homeostasis cannot be maintained
without intervention. The multiple organ dysfunction syndrome is classified as either primary or secondary.

Primary MODS is the result of a well-defined insult in which organ dysfunction occurs early and
can be directly attributable to the insult itself (eg, renal failure due to rhabdomyolysis).
Secondary MODS is organ failure not in direct response to the insult itself, but as a consequence
of a host response. In the context of the definitions of sepsis and SIRS, MODS represents the more
severe end of the spectrum of severity of illness characterized by SIRS/sepsis.

Criteria for the Classification of Wegener's Granulomatosis (WG)

1. Nasal or oral inflammation: Development of painful or painless oral ulcers or purulent or bloody
nasal discharge
2. Abnormal chest radiograph: Chest radiograph showing the presence of nodules, fixed infiltrates,
or cavities
3. Urinary sediment: Microhematuria (>5 red blood cells per high power field) or red cell casts in
urine sediment
4. Granulomatous inflammation on biopsy: Histologic changes showing granulomatous
inflammation within the wall of an artery or in the perivascular or extravascular area (artery or
arteriole)

For purposes of classification, a patient shall be said to have Wegener's granulomatosis if at least 2 of these
4 criteria are present. The presence of any 2 or more criteria yields a sensitivity of 88.2% and a specificity
of 92.0%

Diagnostic Criteria for Wilson's disease

1. Low serum ceruloplasmin levels < 20 mg/dL (Normal range 20-50 mg/dL).
2. Kayser - Fleischer rings in eyes.
3. High liver copper levels > 250 micrograms/g dry weight (Normal range <35 micrograms/g dry
weight).
4. High 24 hr urinary copper levels > 100 micrograms /d or > 1.6 mmol/d (Normal range <50
micrograms/d or < 0.8 mmol/d).
5. Radioisotope copper studies using 64Cu, 67Cu or 65Cu, which assesses ability to incorporate
copper into ceruloplasmin.

Liver biopsy is very helpful for making the diagnosis of Wilson's disease, especially in patients with normal
ceruloplasmin levels and no evidence of Kayser-Fleischer rings. Hepatic copper concentrations greater than
250 micrograms/g dry weight (normal is <35 micrograms) are often found in untreated patients with
Wilson's disease.

Identification of the Wilson's disease gene has made molecular diagnosis of this disease possible, but
population-based screening is not feasible or recommended at this time. Genetic testing probably has had
its biggest impact on screening of first-degree relatives of an affected person.

Classification Criteria for the Diagnosis of Systemic Lupus Erythematosus (SLE)

1. Malar rash: Fixed erythema, flat or raised, over the malar eminences
2. Discoid rash: Erythematous circular raised patches with adherent keratotic scaling and follicular
plugging; atrophic scarring may occur

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 3. Photosensitivity: Exposure to ultraviolet light causes rash
4. Oral ulcers: Includes oral and nasopharyngeal ulcers, observed by physician
5. Arthritis: Nonerosive arthritis of two or more peripheral joints, with tenderness, swelling, or
effusion
6. Serositis: Pleuritis or pericarditis documented by ECG or rub or evidence of effusion
7. Renal disorder: Proteinuria >0.5 g/d or 3+, or cellular casts
8. Neurologic disorder: Seizures or psychosis without other causes
9. Hematologic disorder: Hemolytic anemia or leukopenia (<4000/L) or lymphopenia (<1500/L) or
thrombocytopenia (<100,000/L) in the absence of offending drugs
10. Immunologic disorder: Anti-dsDNA, anti-Sm, and/or anti-phospholipid
11. Antinuclear antibodies: An abnormal titer of ANA by immunofluorescence or an equivalent assay
at any point in time in the absence of drugs known to induce ANAs

Any combination of 4 or more of 11 criteria, well-documented at any time during a patient's history, makes
it likely that the patient has SLE (specificity and sensitivity are 95% and 75%, respectively).

Note: ECG, electrocardiography; dsDNA, double-stranded DNA; ANA, antinuclear antibodies.

Diagnostic Criteria of Infarction in CT Imaging of the Brain in Acute Stroke

Infarction: focal hypodense area, in cortical, subcortical, or deep gray or white matter, following vascular
territory, or watershed distribution. Early subtle findings include obscuration of gray/white matter contrast
and effacement of sulci, or "insular ribbon."

Hemorrhage: hyperdense image in white or deep gray matter, with or without involvement of cortical
surface (40 to 90 HU). Petechial refers to scattered hyperdense points, coalescing to form irregularly
hyperdense areas with hypodense interruptions. Hematoma refers to a solid, homogeneously hyperdense
image.

Hyperdense image in major intracranial artery: suggestive of vascular embolic material.

Calcification: hyperdense image within or attached to vessel wall (>120 HU).

Incidental: silent infarct, subdural collection, tumor, giant aneurysm, arteriovenous malformation.

Diagnostic Criteria of Infarction in MRI of the Brain in Acute Stroke

Acute: Subtle low signal (hypointense) on T1, often difficult to see at this stage, and high signal
(hyperintense) on spin density and/or T2-weighted and proton density-weighted images starting 8 h after
onset; should follow vascular distribution. Mass effect maximal at 24 h, sometimes starting 2 h after onset,
even in the absence of parenchymal signal changes. No parenchymal enhancement with paramagnetic
contrast agent. Territorial intravascular paramagnetic contrast enhancement of "slow-flow" arteries in
hyperacute infarcts; at 48 h, parenchymal and meningeal enhancement can be expected.

Subacute (1 wk or older): Low signal on T1, high signal on T2-weighted images. Follows vascular
distribution. Revascularization and blood-brain barrier breakdown may cause parenchymal enhancement
with contrast agents.

Old (several weeks to years): Low signal on T1, high signal on T2. Mass effect disappears after 1 mo. Loss
of tissue with large infarcts. Parenchymal enhancement fades after several months.

Staging of Prostate Cancer

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The Tumor-Node-Metastasis (TNM) System

Stage (TNM) Definition of Stage

T1 Not palpable, found following TURP or biopsy
T1a Focal, <5% of tissue, not high grade
T1b Diffuse, >5% of tissue, and/or high grade
T1c Biopsy for PSA elevation only
T2 Palpable disease limited to the prostate
T2a Disease < of one lobe
T2b Disease > of one lobe but < 1 lobe
T2c Disease > 1 lobe
T3 Palpable disease beyond the prostate
T3a Unilateral disease beyond the capsule
T3b Bilateral disease beyond the capsule
T3c Spread to seminal vesicles
T4 Metastatic spread to adjacent organs (e.g., bladder, pelvic sidewall)
Metastatic N+ Tumor that has spread to pelvic lymph nodes
cancer M+ Tumor that has spread beyond pelvic lymph nodes

TURP = transurethral resection of the prostate; PSA = prostate-specific antigen.

The Gleason Grading System

The Gleason histological scoring system, tumors are graded from one to five based upon the degree of
glandular differentiation and structural architecture. Grade one represents the most well-differentiated
appearance and grade five represents the most poorly differentiated. A primary score and a secondary score
is then reported. The most differentiated cancers have a score of "one plus one" or two; the most
undifferentiated cancers are scored as "five plus five" or ten. Combined scores (primary and secondary
scores) of two, three, and four usually represent well-differentiated cancers; scores of five, six, or seven
represent moderately differentiated cancers; and scores of eight, nine, or ten represent poorly differentiated
cancers. The prognosis is directly related to the pattern score.

Grading System:
1 Simple round glands, closely packed in rounded masses with well-defined edges.
2 Simple round glands, loosely packed in vague, rounded masses with loosely packed edges.
3A Medium-sized single glands of irregular shape and irregular spacing with ill-defined infiltrating
edges.
3B Very similar to 3A, but small to very small glands which must not form significant chains or cords.
3C Papillary and cribriform epithelium in smooth, rounded cylinders and masses; no necrosis.
4A Small, medium, or large glands fused into cords, chains or ragged, infiltrating masses.
4B Very similar to 4A, but with many large clear cells, sometimes resembling "hypernephroma."
5A No glandular differentiation, solid sheets, cords, single cells, or solid nests of tumor with central
necrosis.
5B Anaplastic adenocarcinoma in ragged sheets.

Diagnostic Criteria for Adult Respiratory Distress Syndrome (ARDS)

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Acute Respiratory Distress Syndrome (ARDS) is a syndrome of inflammation and increased permeability
associated with a constellation of clinical, radiologic, and physiologic abnormalities unexplained by
elevations in left atrial or pulmonary capillary pressure.

All definitions of this syndrome include patients who meet the following criteria:
Identifiable associated condition
Acute onset
Pulmonary artery wedge pressure </=18 mm Hg or absence of clinical evidence of left atrial
hypertension
Bilateral infiltrates on chest radiography
Acute lung injury (ALI) is present if Pao2/Fio2 ratio is </= 300
Acute respiratory distress syndrome is present if Pao2/Fio2 ratio </= 200

ARDS = acute respiratory distress syndrome; Pao2 = partial pressure of arterial oxygen; Fio2 = percentage
of inspired oxygen.

Clinical Conditions Associated with Development of Acute Respiratory Distress Syndrome

Direct lung injury

Pneumonia
Aspiration of gastric contents
Inhalation injury
Near drowning
Pulmonary contusion
Fat embolism
Reperfusion pulmonary edema post lung transplantation or pulmonary embolectomy
Indirect lung injury
Sepsis
Severe trauma
Acute pancreatitis
Cardiopulmonary bypass
Massive transfusions
Drug overdose

Knaus Criteria for Multiple System Organ Failure (MSOF)

Multiple systems organ failure is said present when more than one of the system dysfunctions detected by
test values exceeding the threshold values.

Acute Organ System Dysfunction

Respiratory failure (presence of one or more):

Respiratory frequency <5, >49 (>two years of age)
Alveolar-arterial difference in O2 >350 mmHg or PaO2/ Fi02 <200 (without congenital cardiac
lesion)
Requires mechanical ventilatory support >24 h
PaCO2, >50 mmHg and pHa <7.25
Circulatory failure (presence of one or more):
Heart rate <50/mm or episode of ventricular tachycardia/fibrillation
Mean systemic arterial pressure <50 mmHg and (or) systolic systemic arterial pressure <60 mmHg
Cardiac Index <2 L/min per sq. meter of body surface (acute onset) and (or) pHa <7.25, PaCO2,
<35 without respiratory failure

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Renal failure (presence of one or more):
Urine volume 9.3 mL/kg body weight per hour for 8 h
Serum creatinine >266 umol/L
Urea nitrogen >1.00 g/L or urea >0.60 g/L
Hepatic failure (presence of both):
Bilirubin >60 mg/L or a twofold increase in alkaline phosphatase in serum and
Prothrombin time >4 s over upper limit of normal range or a twofold increase in aspartate
aminotransferase in serum
Hematologic failure (presence of one or more):
Leukocytes <1500/mL or >40000/mL
Platelets <20000/mL or evidence of ongoing disseminated intravascular coagulation
Neurologic failure
Glasgow Coma Scale <6 (without sedation)
Uncontrolled sepsis (presence of one or more):
Positive blood culture despite antibiotic therapy
Fever >39.5 C (rectal temp) for >24 h or spikes on three successive days

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