Myelin basic protein, oligoclonal bands, and IgG in cerebrospinal fluid as indicators of multiple sclerosis

There currently are three clinical laboratory procedures for use with cerebrospinal fluid that assist in the diagnosis of multiple sclerosis: measurement of myelin basic protein and IgG, and demonstration of an oligoclonal band. We compared characteristics of these procedures, using CSF samples from 166 patients identified as having (54 patients) or not having (112 patients) multiple sclerosis. We find that oligoclonal band demonstration is the most useful single test in helping to establish the presence of multiple sclerosis; IgG quantitation is the least helpful. Myelin basic protein should be quantitated for following the activity of multiple sclerosis; it may be applied only selectively in the context of screening. The incidence of false-positive results reinforces the view that the diagnosis of multiple sclerosis must be made in clinical context. These laboratory procedures are not suitable for use as screening tests.     

Venous thrombosis: the clinical problem

Although the exact cause of DVT is not known, venous thrombosis and its sequelae remain important clinical problems. Pulmonary embolism is a significant cause of morbidity and mortality in the hospitalized population, and the postthrombotic syndrome affects a large portion of the general population. While specific screening tests are not readily available to detect those patients who are likely to develop DVT, certain clinical risk factors have been identified that predispose to thrombosis. These groups include patients undergoing a wide variety of surgical procedures, patients with cardiac disease or cancer, pregnant or postpartum women, and individuals with previous history of DVT. The diagnosis of thrombosis is based on clinical findings and must be confirmed with appropriate laboratory tests. While contrast venography remains the gold standard, noninvasive tests have become increasingly more accurate. The recent use of real-time B-mode ultrasonic imaging and duplex sonography for the diagnoses of DVT has been shown to be efficacious. The postthrombotic syndrome with its associated chronic pain and ulcerations remains a significant clinical problem. The general diagnosis of this condition is readily made on clinical grounds in the advanced state. However, exact knowledge of the location and cause of the venous pathology can only be obtained using objective diagnostic tests. Older noninvasive and invasive tests may diagnose the presence of venous obstruction, valvular incompetence, and also may document venous hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnostic approach to the patient with a chronic diarrheal disorder

Chronic diarrhea is a common problem facing the practitioner of medicine. Despite impressive advances in diagnostic technology, many patients continue to have chronic diarrhea without a firm diagnosis being established. Most important, the history and physical examination are often perfunctory and the patient undergoes a number of contrast and imaging studies, endoscopic procedures, and laboratory investigations which may still be non-diagnostic. In all patients with chronic diarrhea, which I will arbitrarily define as diarrhea that has persisted over at least 2 months, there is a need for a careful orderly approach to the differential diagnosis. In this paper I will detail a method that I have used in evaluating such patients. The method emphasizes a careful history and physical examination, judicious and sequential use of laboratory investigations, contrast studies, and endoscopic procedures, and calls attention to special situations where more detailed investigations are required. I have found that unless I go through this detailed diagnostic approach, I will miss disorders that can be readily diagnosed and, more importantly, such patients may not be given appropriate treatment.     

Measures to decrease the risk of acquired immunodeficiency syndrome transmission by blood transfusion. Evidence of volunteer blood donor cooperation

We studied whether volunteers giving blood to the Greater New York Blood Program (GNYBP) cooperated with procedures implementing public health recommendations intended to decrease the risk of acquired immunodeficiency syndrome (AIDS) transmission by blood transfusion. Predonation medical screening was expanded to exclude donors who might be ill with AIDS. To exclude possible asymptomatic carriers of the disease, members of groups at increased risk of AIDS were asked either not to give blood or to give it for laboratory studies. A confidential questionnaire, administered to all donors after medical screening, provided the vehicle for donors to advise the GNYBP whether their donation was for laboratory studies or for patient transfusion. We found that the number of male donors decreased; AIDS-related questions in medical history led to a 2 percent increase in donor rejections; 97 percent of donors said their blood could be used for transfusions; 1.4 percent said their blood could be used for laboratory studies only; and 1.6 percent did not respond. Only units designated for transfusion were released to hospitals. People who indicated that their donation was for laboratory studies had a higher prevalence of markers for hepatitis B virus and of antibodies to cytomegalovirus. White cell counts and helper/suppressor T lymphocyte ratios were not significantly different in the two groups. We conclude that volunteer donors have cooperated with the established procedures. None of the laboratory assays identified blood units donated by individuals who, based on information about AIDS high-risk groups, designated their donation for laboratory studies.     

Roadmap for harmonization of clinical laboratory measurement procedures

Results between different clinical laboratory measurement procedures (CLMP) should be equivalent, within clinically meaningful limits, to enable optimal use of clinical guidelines for disease diagnosis and patient management. When laboratory test results are neither standardized nor harmonized, a different numeric result may be obtained for the same clinical sample. Unfortunately, some guidelines are based on test results from a specific laboratory measurement procedure without consideration of the possibility or likelihood of differences between various procedures. When this happens, aggregation of data from different clinical research investigations and development of appropriate clinical practice guidelines will be flawed. A lack of recognition that results are neither standardized nor harmonized may lead to erroneous clinical, financial, regulatory, or technical decisions. Standardization of CLMPs has been accomplished for several measurands for which primary (pure substance) reference materials exist and/or reference measurement procedures (RMPs) have been developed. However, the harmonization of clinical laboratory procedures for measurands that do not have RMPs has been problematic owing to inadequate definition of the measurand, inadequate analytical specificity for the measurand, inadequate attention to the commutability of reference materials, and lack of a systematic approach for harmonization. To address these problems, an infrastructure must be developed to enable a systematic approach for identification and prioritization of measurands to be harmonized on the basis of clinical importance and technical feasibility, and for management of the technical implementation of a harmonization process for a specific measurand.     

PRENATAL DIAGNOSIS AND DOWN SYNDROME: PART 2. POSSIBLE EFFECTS

The effects of prenatal diagnosis on the birth frequency of Down syndrome are considered through a review of recent literature. Both present and possible future effects are discussed and brief mention of some psychological aspects of prenatal diagnosis is made. The incomplete uptake of amniocentesis is noted; ranging from 20% to over 40% of eligible women in recent British studies; reasons for this are explored. A consideration of reported changes in age specific incidence and their relationship to the introduction and continued use of prenatal diagnosis is given. Reductions in incidence of between 5% and 18% have been reported in the past. The maximum future effects, as predicted by studies using age in conjunction with biochemical screening methods, are noted; detection of up to 60% of affected foetuses is theoretically possible. However, problems of introducing this type of scheme may prevent such effective screening methods being widely adopted. This being the case, it seems unlikely that more than 15% of births affected by Down syndrome will be prevented by prenatal diagnosis in the foreseeable future.     

5·12汶川大地震挤压综合征伤员电解质紊乱特点分析

目的探讨汶川地震挤压综合征伤员电解质紊乱的特点。方法对149例地震挤压综合征伤员的临床特点,尤其是电解质紊乱的特点进行分析。结果与非挤压综合征伤员比较,149例（8.2%）挤压综合征伤员有更严重的肾功能损害,血钾及血磷水平更高,血钙水平更低（P〈0.05）;同时表现出血清天冬氨酸氨基转移酶（AST）、乳酸脱氢酶（LDH）和肌酸激酶（CK）水平显著升高（P〈0.05）;电解质紊乱表现多种多样,包括高钾血症、低钾血症、低钠血症、低钙血症、高磷血症、低磷血症以及代谢性酸中毒,尤其是高钾血症,不但严重而且顽固,需要尽早积极治疗。结论地震后挤压综合征伤员表现出严重而且复杂的电解质紊乱,高钾血症是最严重的表现,需要密切监测和积极治疗。     

Racial and Ethnic Differences in the Presentation of Metabolic Syndrome

This paper explores the effectiveness of the Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) recommendations for diagnosing metabolic syndrome in people from specific racial and ethnic groups. More than 50 million adult Americans have metabolic syndrome. Some racial and ethnic minority groups have much higher percentages of the metabolic syndrome than general population estimates suggest. However, some minority populations in the United States such as Hispanics appear to be underdiagnosed. A literature review was conducted to determine whether the general ATP III guidelines have sufficient screening criteria for detecting metabolic syndrome in various racial and ethnic minority groups. Research articles published in the United States from 2000 to 2005 were reviewed. Studies were included that presented data related to black, Hispanic, and Asian American male and female subjects older than age 18. Waist circumference appears to be the most predictive screening factor among the metabolic syndrome criteria. Patients with normal body mass indexes may still have elevated waist circumferences that meet the ATP III risk criteria for metabolic syndrome. Blacks have high rates of hypertension even without considering metabolic syndrome, and they may have more disease risk than other populations. Hispanics have an increased risk of diabetes associated with metabolic syndrome. Because the criteria may not be sufficient to diagnose metabolic syndrome in Asian Americans as a result of different body types, the diagnosis might be missed in this group. There is a need for more research on how the diagnosis of metabolic syndrome presents in different racial and ethnic minority groups in the United States. Practitioners need evidence-based screening tools that will provide the most accurate information for evaluating persons of racial and ethnic groups who are most at risk of diabetes, cardiovascular disease, and stroke. The determination of the applicability of screening criteria to diverse patient populations is vital to providers who are obligated to provide culturally competent care to their patients. This paper synthesizes selected literature and presents recommendations to assist nurse practitioners in the assessment of metabolic syndrome in specific racial and ethnic minority groups.     

Diagnosis in an acute organophosphate poisoning: report of three interesting cases and review of the literature.

Organophosphates may cause serious life-threatening conditions, such as an initial acute cholinergic crisis and intermediate syndrome. Each of these conditions has a potential for respiratory failure requiring ventilatory support. For this reason, it is very important to recognize them early, especially to institute appropriate management. The diagnosis of organophosphate poisoning is based essentially on a clinical assessment, followed by laboratory examinations. Sometimes the diagnosis may be difficult, as in case 1, identified initially as brainstem stroke. However, if neurological syndromes associated with organophosphate poisoning are well known, they can easily be distinguished from other conditions that resemble them. Two cases displayed the symptoms and signs of intermediate syndrome; however, one case (no. 2) did not have severe poisoning on admission but needed artificial ventilation. Each case recovered completely from organophosphate poisoning as a result of early diagnosis and appropriate therapy. Therefore, we would like to describe the clinical and laboratory features of these syndromes, observed in three interesting cases, and to emphasize the importance of early and accurate diagnosis for the appropriate management of acute organophosphate poisoning.     

Evaluation of incidental renal and adrenal masses

Incidental renal or adrenal masses are sometimes found during imaging for problems unrelated to the kidneys and adrenal glands. Knowledgeable family physicians can reliably diagnose these masses, thereby avoiding unnecessary worry and procedures for their patients. A practical and cost-efficient means of evaluating renal lesions combines ultrasonography and computed tomographic scanning, with close communication between the family physician and the radiologist. Asymptomatic patients with simple renal cysts require no further evaluation. Patients with minimally complicated renal cysts can be followed radiographically. Magnetic resonance imaging is indicated in patients with indeterminate renal masses, and referral is required in patients with symptoms or solid masses. The need for referral of patients with adrenal masses is determined by careful assessment of clinical signs and symptoms, as well as the results of screening laboratory studies and appropriate radiologic studies. Referral is indicated for patients with incidental adrenal masses more than 6 cm in greatest diameter. Appropriate laboratory screening tests include the following: a 24-hour urinary free cortisol measurement for patients with evidence of Cushing's syndrome; a 24-hour urinary metanephrine, vanillylmandelic acid or catecholamine measurement for patients with evidence of pheochromocytoma; and a serum potassium level for patients with evidence of hyperaldosteronism.     

Layered peptide arrays: high-throughput antibody screening of clinical samples

High-throughput methods to detect and quantify antibodies in sera and other patient specimens have use for many clinical and laboratory studies, including those associated with cancer detection, microbial exposures, and autoimmune diseases. We developed a new technique, termed layered peptide array (LPA), to serve as a screening tool to detect antibodies in a highly multiplexed format. We demonstrate here that a prototype LPA was capable of producing approximately 5000 measurements per experiment and appeared to be scalable to higher throughput levels. Sera and saliva from Sj?gren's syndrome patients served as a test set to examine antibody titers in clinical samples. The LPA platform exhibited both a high sensitivity (100%) and high specificity (94%) for correctly identifying SSB antigen-positive samples. The multiplex capability of the platform was also confirmed when serum and saliva samples were analyzed for antibody reactivity to several peptides, including Sj?gren's syndrome antigens A and B. The data indicate that LPA analysis will be a useful method for a number of screening applications.     

Antiphospholipid syndrome and its role in pediatric cerebrovascular diseases: A literature review

Antiphospholipid syndrome (APS) or Hughes syndrome is an acquired thromboinflammatory disorder. Clinical criteria of APS diagnosis are large- and small-vessel thrombosis as well as obstetric problems; laboratory criteria are the presence of antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies and anti-β2-glycoprotein-1). The presence of at least 1 clinical and 1 laboratory criterion allows definitive diagnosis of APS. Primary APS is diagnosed in patients without features of connective tissue disease; secondary APS is diagnosed in patients with clinical signs of autoimmune disease. A high frequency of catastrophic APS as well as a high tendency to evolve from primary APS to secondary syndrome during the course of lupus and lupus-like disease is a feature of pediatric APS. The most characteristic clinical presentation of APS in the pediatric population is venous thrombosis, mainly in the lower limbs, and arterial thrombosis causing ischemic brain stroke. Currently, no diagnostic criteria for pediatric APS exist, which probably results in an underestimation of the problem. Similarly, no therapeutic procedures for APS specific for children have yet been established. In the present literature review, we discussed data concerning APS in children and its role in cerebrovascular diseases, including pediatric arterial ischemic stroke, migraine and cerebral venous thrombosis.     

5·12汶川大地震挤压综合征伤员电解质紊乱特点分析

目的 探讨汶川地震挤压综合征伤员电解质紊乱的特点.方法 对149例地震挤压综合征伤员的临床特点,尤其是电解质紊乱的特点进行分析.结果 与非挤压综合征伤员比较,149例(8.2%)挤压综合征伤员有更严重的肾功能损害,血钾及血磷水平更高,血钙水平更低(P＜0.05);同时表现出血清天冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH)和肌酸激酶(CK)水平显著升高(P＜0.05);电解质紊乱表现多种多样,包括高钾血症、低钾血症、低钠血症、低钙血症、高磷血症、低磷血症以及代谢性酸中毒,尤其是高钾血症,不但严重而且顽固,需要尽早积极治疗.结论 地震后挤压综合征伤员表现出严重而且复杂的电解质紊乱,高钾血症是最严重的表现,需要密切监测和积极治疗.     

Neonatal screening for metabolic and endocrine diseases

The screening of neonates for metabolic diseases is important in order to identify a population with or at risk for metabolic diseases. Early diagnosis can then be made, treatment instituted and physical and/or mental handicaps due to the disease can be prevented. The World Health Organization's screening criteria are helpful in selecting those diseases appropriate for screening. Usually a state-designated central laboratory performs the screening tests. All states screen for phenylketonuria (PKU) and hypothyroidism; in addition, 26 states screen for galactosemia, 20 for maple syrup urine disease and 19 for homocystinuria. The cost-benefit ratio for screening programs is excellent, varying from 1:13 to 1:20. The necessary follow-up of patients for diagnosis and treatment can be enhanced by maintaining a close liaison with the laboratory and providing adequate information to parents. As a result of instituting a screening program, the incidence of mental retardation due to PKU has been practically eliminated and new insights about metabolic diseases have been obtained. The rapid progress in technology may soon result in better and cheaper tests capable of identifying more diseases amenable to treatment.     

Accuracy of a prediction model for heparin-induced thrombocytopenia (HIT): an analysis based on individual patient data

BackgroundHeparin-induced thrombocytopenia (HIT) is an adverse drug reaction associated with thrombosis, and its paradoxical nature is a challenging issue for the diagnosis. The ‘4Ts’ scoring system represents a simple and efficient way to improve clinical diagnoses of the syndrome. This system classifies patients as having high, intermediate, and low clinical probability for HIT. However, uncertainty remains concerning its clinical meaning, thus weakening the diagnostic value of this screening instrument.MethodsWe analyzed the diagnostic test accuracy based on individual patient data extracted from published primary scientific studies. This study focused on 186 cases of treatment with heparin, which later evolved into a clinical suspicion of HIT. Upon choosing the most appropriate reference laboratory, the accuracy of the 4Ts was analyzed using the receiver operator characteristic curve analysis.ResultsHalf of the positive cases (57.1%) were classified as having a high score, while 25.5% of the negative cases were classified as a having low score for HIT. Slightly more than half of all patients (53.2%) were classified as having an intermediate score. As such, the pre-test instrument would most likely fail to distinguish between diseased and nondiseased patients in a relevant number of cases. The calculated accuracy of the summary indicates that the 4Ts can be considered a good, but not a defining, test.ConclusionFurther studies are warranted regarding clinical score systems, either alone or in combination with laboratory tests, in an attempt to improve the early diagnosis of this adverse drug reaction and to provide better care for at-risk patients.     

广西地区纯合子血红蛋白Constant Spring的研究

目的　分析广西地区纯合子血红蛋白ConstantSpring(HbCS)的表现型与基因型的相互关系 ,探讨临床上可能的漏诊原因及其筛查和确诊方法。方法　醋酸纤维薄膜电泳后联苯胺染色法筛选HbCS ,用PCR方法和DNA测序确诊纯合子HbCS基因突变。结果　 9例患者中 ,4例完全无临床症状 ,2例有轻度贫血、脾肿大 ,3例有轻度至中度巩膜黄染。血红蛋白正常或有轻度贫血 ,MCV正常或降低。全部病例外周血涂片呈红细胞大小不等 ,中央浅染 ,有靶形红细胞。血红蛋白分析HbA2 HbCS 4 .3%～ 6 .7% ,HbA2 <2 .0 % ,多数为 1.4 % ,基因分析确诊为纯合子HbCS。结论　纯合子HbCS的临床表现、血液学改变和血红蛋白分析方面差异很大 ,可以完全无症状 ,血液学资料正常或仅有轻度黄疸 ,亦可类似于HbH病。此病在临床上较易漏诊、误诊。确诊依赖基因分析。     

介绍一种诊断明确时定性检测方法的性能评估方案

目的建立一种诊断明确时定性检测方法的性能评估方案。方法采用比较分析的方法，分别将新方法和原方法的检测结果与明确诊断结果进行比较。结果以实例的方式将新方法、原方法的检测结果和诊断结果进行比较，得出性能较好的定性检测方法。结论定性检测是临床实验室一种很重要的检测方法，其检测性能如何直接决定患者的检测结果，该评估方法的提出为临床实验室引入一种新的检测方法提供了指南。     

The Central Sensitization Inventory (CSI): Establishing Clinically Significant Values for Identifying Central Sensitivity Syndromes in an Outpatient Chronic Pain Sample

Central sensitization (CS) is a proposed physiological phenomenon in which central nervous system neurons become hyperexcitable, resulting in hypersensitivity to both noxious and non-noxious stimuli. The term central sensitivity syndrome (CSS) describes a group of medically indistinct (or nonspecific) disorders, such as fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome, for which CS may be a common etiology. In a previous study, the Central Sensitization Inventory (CSI) was introduced as a screening instrument for clinicians to help identify patients with a CSS. It was found to have high reliability and validity (test-retest reliability = .82; Cronbach's alpha = .88). The present study investigated a cohort of 121 patients who were referred to a multidisciplinary pain center, which specializes in the assessment and treatment of complex pain and psychophysiological disorders, including CSSs. A large percentage of patients (n = 89, 74%) met clinical criteria for one or more CSSs, and CSI scores were positively correlated with the number of diagnosed CSSs. A receiver operating characteristic analysis determined that a CSI score of 40 out of 100 best distinguished between the CSS patient group and a nonpatient comparison sample (N = 129) (area under the curve = .86, sensitivity = 81%, specificity = 75%).PerspectiveThe CSI is a new self-report screening instrument to help identify patients with CSSs, including fibromyalgia. The present study investigated CSI scores in a heterogeneous pain population with a large percentage of CSSs, and a normative nonclinical sample to determine a clinically relevant cutoff value.     

A review of the clinical presentation and laboratory findings in two uncommon hereditary disorders of sulfur amino acid metabolism, beta-mercaptolactate cysteine disulfideuria and sulfite oxidase deficiency

Two hereditary disorders of sulfur amino acid metabolism, beta-mercaptolactate-cysteine disulfideuria and sulfite oxidase deficiency, were described twenty years ago. Other examples of these disorders have been limited to about 5 of each in the world literature since then. Reasons for the apparent rarity of these conditions are discussed and the analytical procedures to identify them are reviewed. The detection of the first depends on the positive result of a cyanide-nitroprusside test followed by positive identification of the specific mixed disulfide. The enzyme mercaptopyruvate sulfur transferase has been shown to be deficient. In the second disorder of sulfite oxidase deficiency, the clinical presentation with progressive dystonia and dislocated lenses in an infant should suggest further laboratory investigations for this disorder which would not be detected by conventional laboratory screening procedures. Laboratory diagnosis can be obtained by use of the Merckoquant sulfite test on a fresh urine sample. Quantitative thiosulfate and taurine measurements can also be made. Positive identification of the specific amino acid S-sulfo-L-cysteine should also be made. The enzyme sulfite oxidase is missing from such organs as liver, kidney and brain. This latter condition may also be associated with xanthinuria. For this combined disorder of sulfite oxidase and xanthine oxidase, a deficiency of a molybdenum-containing cofactor has been demonstrated.     

Laboratory studies in the evaluation of urologic disease: Part I

This is the first of a two-part article reviewing basic laboratory, imaging, endoscopic, urodynamic, and miscellaneous studies used for screening and diagnosis of urologic disease. Normal values, recommended collection procedures, and interpretation of results are also reviewed. This initial installment deals with laboratory tests used in urologic disease.