"Best calcitriol 0.25mcg, medicine 5277".

N. Makas, M.B. B.A.O., M.B.B.Ch., Ph.D.

Program Director, Northwestern University Feinberg School of Medicine

This is because there are proportionally more scores closer to the mean than farther from the mean. The non-linear relation between z scores and percentiles has important interpretive implications. For example, a one-point difference between two z scores may be interpreted differently, depending on where the two scores fall on the normal curve. The difference between a z score of 0 and a z score of +1 is 34 percentile points, because 34% of scores fall between these two z scores. However, the difference between a z score of +2 and a z score of +3 is less than 3 percentile points, because only 2. The interpretation of percentile scores with an equivalent "difference" between two percentile rankings might have very different clinical implications if the scores occur at the tail end of the curve versus near the middle of the distribution. For example, an improvement in a standard score from the 5th percentile to the 30th percentile (25 percentile points), compared to an improvement from the 37th to the 62nd percentile (25 percentile points), (1) requires a greater improvement in performance from a standard score perspective. Ceiling/Floor Effects and Score Comparisons Floor and ceiling effects may be defined as the presence of truncated tails in the context of limitations in range of item difficulty. For example, a test may be said to have a high floor when a large proportion of the examinees obtain raw scores at or near the lowest possible score. This may indicate that the test lacks a sufficient number and range of easier items. Conversely, a test may be said to have a low ceiling when the opposite pattern is present. For example, a measure with a high floor may not be suitable for use with low functioning examinees, particularly if one wishes to delineate level of impairment. Misinterpreting results obtained from tests with 31 Psychometric Foundations for the Interpretation of Neuropsychological Test Results 905 low ceilings is common. Thus, it likely better reflects no evidence of non-compliance with the assessment, or "adequate," "normal," or even "minimal" effort. A similar situation occurs with the Boston Naming Test where a score of 60/60 should be considered as reflecting average, not excellent, naming ability. If a clinician is not well informed of the distribution of test scores, floor and ceiling effects can potentially lead to misinterpretations when comparing across tests. The Boston Diagnostic Aphasia Exam Complex Ideation test (Goodglass and Kaplan 1983) measures language comprehension and short-term memory. A perfect score of 12 is achieved by a large percentage of healthy adults, and performance varies considerably based on level of education. This truncation represents a "ceiling effect" in that the test does not measure a broad range of performance in high functioning adults. Extrapolation/Interpolation of Derived Scores There are times when norms fall short in terms of range or cell size. This includes missing data in some cells, inconsistent age coverage, or inadequate demographic composition of some cells compared to the population. In these cases, data are often extrapolated or interpolated using the existing score distribution and techniques such as multiple regression. For example, Heaton and colleagues have published sets of norms that use multiple regression to correct for demographic characteristics and compensate for few subjects in some cells (Heaton et al. Although multiple regression is robust to slight violations of assumptions, estimation errors may occur when using normative data that violates the assumptions of homoscedasticity (uniform variance across the range of scores) and the distribution of residuals that are necessary for multiple regression are non-normal (Fastenau and Adams 1996). Age extrapolations beyond the bounds of the actual ages of the individuals in the samples are occasionally seen in published datasets, based on projected developmental curves. These norms should be used with caution due to the lack of actual data points in these age ranges. Thus, including only a subset of the distribution of age scores in the regression. Tests that appear to have linear relationships, when considered only in adulthood, may actually have highly nonlinear relationships when the entire age range is considered. One example is vocabulary, which tends to increase exponentially during the preschool years, shows a slower rate of progress during early adulthood, remains relatively stable with continued gradual increase, and then shows a minor decrease with advancing age. Rule of thumb: Comparison of test scores across tests Comparison of performance across tests is affected by: · Measurement error · Score magnitude and rank in the distribution · Extreme scores · Ceiling and floor effects · Extrapolation/interpolation of derived scores.

Diseases

• Leukodystrophy, metachromatic
• Laurence Prosser Rocker syndrome
• His bundle tachycardia
• Paget disease extramammary
• Essential thrombocythemia - synonym of Essential thrombocytosis
• Split hand split foot X linked
• Potassium deficiency (hypokalemia)

Cell dysfunction or death may occur even in the absence of any inflammatory or immune response. Furthermore, within each of these categories, specific viral illnesses may have individual clinical features that strongly suggest the diagnosis. To compound the complexity, certain viruses can cause different pathologic changes in the brain depending on the setting. For example, acute toxic encephalopathy, parainfectious encephalomyelitis, subacute sclerosing panencephalitis, and subacute measles encephalitis were all reported to be caused by the measles virus (although now this is rarely seen). Despite these difficulties in diagnosis, an attempt should be made to separate the acute encephalitides into pathologic categories and to establish the causal agent, since the treatment and prognosis are different in the different categories. Neuronal destruction is accompanied by perivascular invasion with inflammatory cells and proliferation of microglia with frequent formation of glial nodules. Areas of focal cortical necrosis are Acute Viral Encephalitis Although a number of viruses cause human encephalitis, only two major types are both common and produce coma in the United States: arboviruses (Eastern equine, Western equine, and St. Cowdry type A inclusion bodies in neurons and glial cells are a distinctive feature. Clinically, herpes simplex encephalitis begins with the acute onset of a confusional state, aphasia, or behavioral changes, often accompanied by headache, fever, and seizures. In one series of 45 patients, 28 had Glasgow Coma Score of less than 10 and 13 were deeply comatose. Often, behavioral disturbances or agitated delirium, particularly with olfactory or gustatory hallucinations, precedes coma by hours or days, a pattern so characteristic as to suggest the diagnosis. Focal motor signs frequently accompany the onset of coma, and tremors of the extremities, face, and even trunk commonly complement the agitated delirium of herpes encephalitis. Occasionally the neurologic signs of herpes simplex encephalitis, either type 1415 or type 2,416, are limited to the brainstem, with cranial nerve palsies predominating. Distinctive, periodic, high-voltage, 1-Hz sharp waves from one or both temporal lobes are highly characteristic of herpes simplex encephalitis and suggest a poor prognosis. Abnormalities in the temporal lobes, and sometimes the frontal lobe as well, suggest the diagnosis. Sometimes, as in the following cases, severe hemispheral brain swelling produces transtentorial herniation and may lead to death. Patient 5­24 A 71-year-old woman was brought into the emergency department for a headache and confusion. Her temperature was 988F and she complained of a diffuse headache, but could not answer questions coherently. Neurologic examination showed a mild left hemiparesis and some left-sided inattention. The following day her temperature spiked to 1028F, and a lumbar puncture was done showing seven white blood cells, 19 red blood cells, a protein of 48, and a glucose of 103 with a normal opening pressure. By this time she had lapsed into a stuporous state, with small but reactive pupils, full roving eye movements, and symmetric increase in motor tone. Despite treatment she developed edema of the right temporal lobe with uncal herniation. Comment: Because the initial presentation suggested a right hemisphere ischemic event, the patient was treated according to standard stroke protocols, which do not require lumbar puncture. It is presented because it illustrates the natural history of herpes encephalitis and included a pathologic examination. She had felt vaguely unwell 5 Multifocal, Diffuse, and Metabolic Brain Diseases Causing Delirium, Stupor, or Coma days before admission and then developed occipital headache and vomiting. Two days before admission, a physician carefully examined her but found only a temperature of 398C and a normal blood count. She remained alone for the next 48 hours and was found unconscious in her room and brought to the emergency department. Examination showed an unresponsive woman with her head and eyes deviated to the right. The right pupil was slightly larger than the left, both reacted to light, and the oculocephalic reflex was intact. Her extremities were flaccid, the stretch reflexes were 3ю, and the plantar responses were flexor. In the emergency department she had a generalized convulsion associated with deviation of the head and the eyes to the left. A right carotid arteriogram showed marked elevation of the sylvian vessels with only minimal deviation of the midline structures.

Consequently, few, if any, chylomicrons or chylomicron remnants are present in the blood after a 12-h fast, except in patients with disorders of chylomicron metabolism. During this process, most of the triglyceride in the particle is hydrolyzed, and all apolipoproteins except apoB100 are transferred to other lipoproteins. Apo(a) is synthesized in the liver and attached to apoB100 by a disulfide linkage. The major site of clearance of Lp(a) is the liver, but the uptake pathway is not known. In the liver, cholesterol is excreted into the bile, either directly or after conversion to bile acids. This pathway transports excess cholesterol from the periphery back to the liver for excretion in the bile. A classification scheme based on the molecular etiology and pathophysiology of the lipoprotein disorders complements this system and forms the basis for this chapter. The identification and characterization of genes responsible for the genetic forms of hyperlipidemia have provided important molecular insights into the critical roles of structural apolipoproteins, enzymes, and receptors in lipid metabolism (Table 21-4). It has a higher incidence in certain founder populations, such as Afrikaners, Christian Lebanese, and French Canadians. Total cholesterol levels are usually >500 mg/dL and can be higher than 1000 mg/dL. Atherosclerosis often develops first in the aortic root, where it can cause aortic valvular or supravalvular stenosis, and typically extends into the coronary ostia, which become stenotic. Carotid and femoral disease develops later in life and is usually not clinically significant. Liver transplantation, however, is associated with substantial risks, including the requirement for long-term immunosuppression. Corneal arcus is common, and tendon xanthomas involving the dorsum of the hands, the elbows, the knees, and especially the Achilles tendons are present in ~75% of patients. The clinical diagnosis is usually not problematic, but it is critical that hypothyroidism, nephrotic syndrome, and obstructive liver disease be excluded before initiating therapy. These genes are expressed in the intestine and liver, where they form a functional complex and pump plant sterols, such as sitosterol and campesterol, and animal sterols, predominantly cholesterol, from enterocytes into the gut lumen and from hepatocytes into the bile. In normal individuals, <5% of dietary plant sterols are absorbed by the proximal small intestine and delivered to the liver. Plant sterols that are carried to the liver on chylomicrons are preferentially secreted into the bile such that the plant sterol levels in plasma and tissues are normally very low. In sitosterolemia, the intestinal absorption of plant sterols is increased and biliary excretion of the sterols is reduced, resulting in increased plasma and tissue levels of sitosterol and other plant sterols. Episodes of hemolysis, presumably secondary to the incorporation of plant sterols into the red blood cell membrane, are a distinctive clinical feature of this disease. The hypercholesterolemia in subjects with sitosterolemia is unusually responsive to reductions in dietary cholesterol content. Sitosterolemia should be suspected in patients in whom the plasma cholesterol level falls more than 40% on a low-cholesterol diet. Sitosterolemia is confirmed by demonstrating an increase in the plasma level of sitosterol using gas chromatography. Treatment of polygenic hypercholesterolemia is identical to that of other forms of hypercholesterolemia. Genetic deficiency or inactivity of either protein results in impaired lipolysis and profound elevations in plasma chylomicrons. In these disorders, called familial chylomicronemia syndromes, fasting triglyceride levels are almost invariably >1000 mg/dL. On funduscopic examination the retinal blood vessels are opalescent (lipemia retinalis). Eruptive xanthomas, which are small, yellowish-white papules, often appear in clusters on the back, buttocks, and extensor surfaces of the arms and legs.

Niacin potentiates the effect of warfarin, and these two drugs should be prescribed together with caution. Acanthosis nigricans, a dark-colored coarse skin lesion, and maculopathy are infrequent side effects of niacin. Niacin is contraindicated in patients with peptic ulcer disease and can exacerbate the symptoms of esophageal reflux. It can also raise plasma levels of uric acid and precipitate gouty attacks in susceptible patients. However, in one study in type 2 diabetics, niacin treatment was associated with only a slight increase in fasting glucose and no significant change from baseline in the HbA1C. Thus, niacin can be used in diabetic patients, but every effort should be made to optimize the diabetes management before initiating niacin, and glucose should be carefully monitored in nondiabetic patients with impaired fasting glucose after initiation of niacin therapy. Successful therapy with niacin requires careful education and motivation on the part of the patient. Myopathy and hepatitis occur rarely in the absence of other lipid-lowering agents. Fibrates promote cholesterol secretion into bile and are associated with an increased risk of gallstones. Importantly, fibrates can potentiate the effect of warfarin and certain oral hypoglycemic agents, so the anticoagulation status and plasma glucose levels should be closely monitored in patients on these agents. As noted above, the clinical trial data with fibrates overall suggests cardiovascular benefit, but the results are mixed. In this setting, the risk of myopathy must be carefully weighed against the clinical benefit of the therapy. Fish oil supplements can be used in combination with fibrates, niacin, or statins to treat hypertriglyceridemia. In general, fish oils are well tolerated and appear to be safe, at least at doses up to 3­4 g. Although fish oil administration is associated with a prolongation in the bleeding time, no increase in bleeding has been seen in clinical trials. In this setting, a cholesterol absorption inhibitor or bile acid sequestrant can be added. Coadministration of statins and fibrates has obvious appeal in patients with combined hyperlipidemia, but no clinical trials have assessed the effectiveness of a statinfibrate combination compared with either a statin or a fibrate alone in reducing cardiovascular events, and the long-term safety of this combination is not known. Statin-fibrate combinations are known to be associated with an increased incidence of severe myopathy (up to 2. This combination of drugs should be used cautiously in patients with underlying renal or hepatic insufficiency; in the elderly, frail, and chronically ill; and in those on multiple medications. A larger group of patients, most of whom have genetic lipid disorders, remain significantly hypercholesterolemic despite combination drug therapy. Smoking should be discontinued, obese persons should be encouraged to lose weight, sedentary persons should be encouraged to exercise, and diabetes should be optimally controlled. Nevertheless, the concept is useful because the tumors have important similarities as well as some differences (Table 22-1). They can be tentatively identified on routine histology; however, these tumors are now principally recognized by their histologic staining patterns due to shared cellular proteins. Historically, silver staining was used and tumors were classified as showing an argentaffin reaction if they took up and reduced silver, or as being argyrophilic if they did not reduce it. More recently immunocytochemical localization of chromogranins (A, B, C), neuron-specific enolase, or synaptophysin, which are all neuroendocrine cell markers, are used (Table 22-1). Ultrastructurally, these tumors possess electron-dense neurosecretory granules and frequently contain small clear vesicles that correspond to synaptic vesicles of neurons. Chromogranins (A, B, C) are acidic monomeric soluble proteins found in the large secretory granules; chromogranin A is most widely used. Synaptophysin is an integral membrane glycoprotein of 38,000 molecular weight found in small vesicles of neurons and neuroendocrine tumors. Frequently synthesize multiple peptides/amines, which can be detected immunocytochemically but may not be secreted. Presence or absence of clinical syndrome or type cannot be predicted by immunocytochemical studies. Histologic classifications do not predict biologic behavior; only invasion or metastases establishes malignancy.