Drug effects on clinical laboratory tests

Drugs and xenobiotics can affect clinical laboratory test results either by interfering with the analytical systems themselves, or by influencing endogenous constituents. National and international bodies have brought widespread recognition to this problem and have proposed protocols for its thorough scientific study. In this survey the authors discuss studies in their laboratories concerning the effects of drugs on thousands of patients undergoing a routine clinical screen. A database is described for storing both patient information and a detailed analysis of the published literature on drug effects. Analytical interferences in clinical tests must be examined in validating the procedure. However, highly specific analytical techniques are increasingly helping to reduce such interferences. Biological effects can be classified as physiological, pharmacological or toxicological. In some cases, biological effects can be used to advantage in monitoring treatment by potentially hazardous drugs, such as the cardiac glycosides. The requirement for a well-defined reference population for each drug and for access to all clinical and medical data for each patient is discussed. The need for greater awareness of the influence of drugs on clinical laboratory results is considered, together with the suggestion that the health professions should try to exploit such effects in monitoring possible toxicity problems, in defining genetic constitution and in designing medication programmes.     

Drug interferences with clinical laboratory tests

The interpretation of clinical laboratory tests is dependent on a host of physiological, environmental and pharmacological factors. At present, it is difficult to determine which of these broad groups is involved when one suspects interference with a clinical laboratory test. Detailed knowledge of the drugs that a patient is consuming is critical in understanding potential interferences. Drugs affect laboratory tests by 2 basic mechanisms: (a) physiological or pharmacological interference, and (b) chemical interference. The major interferences with routine clinical chemistry tests are described in the review which follows. The diversity of therapeutic agents that influence tests, points to the problem of monitoring drug interferences. Awareness of the problem and careful review of drug histories is at present the only realistic method of attempting to minimise the problem. Future use of computer data bases may allow potential drug interferences to be signalled automatically.     

Encephalopathy in toxicity tests on laboratory animals

Clinical signs of encephalopathy followed administration of lethal doses of a wide range of drugs, foods, pesticides and other agents in 92 reviewed studies on laboratory animals. Common signs of depression of the brain were anorexia, hypokinesia, hypothermia, prostration, ataxia, pallor, and hyporeflexia and of stimulation were convulsions, hyperreflexia, tremors, muscular spasms, and fever. Less common signs included catalepsy, exophthalmos, phonation, piloerection, bradypnea, tachypnea, automatism, flaccidity, a Straub reaction, erection of the penis, nystagmus, spacial disorientation, and hunch back. Aggressiveness took the form of fighting when animals were aggregated and occasionally automutilation when segregated. Certain signs such as vomiting and panting occurred only in cats and dogs. In chronic studies at sublethal daily doses, there were relatively few signs of encephalopathy. At autopsy, the brain was found relatively resistant to changes in weight, to hydration and to dehydration. Histologically there was no evidence of tissue encephalopathy in a third to a half of the studies. In the remaining studies, the brain was found to have participated in the general inflammatory reaction (capillary or capillary-venous congestion) to toxic doses of the agent under study. Less common histopathological reactions included thrombosis, edema, granulocytic infiltrative meningitis and cerebral abscesses.     

实验室检查在多发性骨髓瘤单克隆免疫球蛋白中的诊断价值

目的探讨多发性骨髓瘤单克隆免疫球蛋白(M蛋白)的临床诊断价值。方法采用免疫固定电泳(IFE)、血清蛋白电泳(SPE)及免疫球蛋白定量(Ig)技术检测105例多发性骨髓瘤患者的血清和尿液,其中10例MM患者进行自体骨髓移植,对其血清M蛋白的表达进行跟踪检测。结果 105例多发性骨髓瘤患者血清免疫固定电泳M蛋白105例阳性,阳性率为100.0%;尿本周氏蛋白阳性76例,阳性率为72.4%(76/105)。25例血清M蛋白为轻链型患者尿本周蛋白阳性率为92.0%(23/25);血清蛋白电泳78例出现M带,检出率为74.3%(78/105);免疫球蛋白定量68例显著升高,阳性率为64.8%(68/105)。结论免疫固定电泳检测M蛋白对诊断MM具有高度的敏感性和特异性,是M蛋白定性和分型的重要指标;血清蛋白电泳和免疫球蛋白定量检测M蛋白可早期筛查MM,减少误诊或漏诊;三项指标联合检测M蛋白对MM的诊断、病情监测、疗效评估及预后判断提供重要依据。     

The role of laboratory tests in alcoholism treatment

Although assessment in the field of alcoholism treatment is generally verbal in nature, biological tests can also provide counselors and program evaluators useful and unique information. Five such laboratory measures are briefly described, with particular emphasis on carbohydrate deficient transferrin, a biomarker recently approved by the FDA. Applications for laboratory tests in alcohol screening, motivating patients, and monitoring treatment progress are also proposed.     

The selection of laboratory tests for organ dysfunctions using multivariate statistics.

There is a need for selecting good combinations of laboratory tests for various medical decision situations. Multivariate statistical methods are better tools for this type of selection than multiple univariate comparisons of candidate tests. Linear discriminant analysis is a suitable method. The best selection strategies are stepwise selection and evaluation of all possible subsets. Guiding criteria in the selection process may be measures of statistical separation between the clinical groups or empirical probabilities of correct reallocation. The latter criterion has the advantage that an optimum subset size may be identified.     

Combination of single-species laboratory tests for the assessment of the ecotoxicity of p-Benzoquinone

The combination of 15 single-species laboratory tests (6 bacteria, 1 Dinoflagellate, 5 yeasts, 2 Crustacea, and 1 fish) was used for the assessment of the ecotoxicological effects of p-benzoquinone. Marked differences were observed in the susceptibility among the species since the toxicity values were ranged between 0.020 mg/L (Photobacterium phosphoreum) and >700 mg/L (Candida parapsilosis). These results support the philosophy that for assessing toxicity more thoroughly, a battery of several tests carried out with organisms occupying different trophic levels in the environment is required.     

Indications for immunotherapy

Underlying immunodeficiency should be suspected in every patient, irrespective of age, who has recurrent, persistent, severe, or unusual infections. Defects in immunity can be classified into primary or secondary disorders involving specific or nonspecific immune mechanisms. Several forms of primary and secondary immunodeficiency exist for which various immunotherapeutic modalities are available. Significant among these are immunoglobulins commercially available for intravenous infusion. Other therapies include transplantation of tissue such as bone marrow, fetal liver, and fetal thymus. Enzyme replacement therapy is being developed, as is the use of products unique to immunocompetent cells, such as thymus extract, thymosin, interleukins, and transfer factor. Forms of nonspecific immune modulators and stimulators are other possibilities, especially in the context of the immunotherapy of tumors.     

Harmonization of thresholds for primary skin irritation from results of human repeated insult patch tests and laboratory animal skin irritation tests

Classification of a chemical or chemical product as a primary skin irritant using laboratory animal tests has been defined rigorously and codified in Consumer Products Safety Commission (CPSC) regulations. However, no regulatory agency, including the CPSC, has defined a primary skin irritant threshold for human repeat insult patch tests (RIPTs) that are typically conducted on products, such as cosmetics, anticipated to come into direct contact with humans. Further more, the protocols for animal and human tests are significantly different, as are the schemes for grading responses. Consequently, comparing the results of one type of test with those from the other type has proved to be difficult. In this short communication, we propose a procedure to harmonize the results from these two types of skin irritation tests and suggest that a score of "5" in animal tests, considering 24-h results on unabraded skin, is equivalent to a score of "3" in human RIPTs.     

Indications for lipid-lowering drugs

Summary There is overwhelming evidence from prospective studies that plasma cholesterol levels are exponentially related to coronary artery disease (CAD) risk. Inversely, the beneficial effect of lowering plasma cholesterol is convincingly established from major clinical trials. A consensus has been reached in a large number of countries on the need to lower plasma lipid levels, especially LDL-cholesterol, to delay the onset, slow the progression and induce regression of atherosclerotic lesions in the coronary arteries. This remains the major indication of lipid-lowering therapy. In recent years, the emphasis has been put on target plasma lipid concentrations for dietary and drug therapy. In the process of establishing prevention strategies, however, some confusion arose: target values and criteria for assessing CAD risk and initiating therapy have differed from country to country, as well as among various groups within a country. Population strategies and high-risk case-finding strategies have clashed. Treatment algorithms have emphasized lipid levels rather than lipid transport disorders. With time, these algorithms have become more and more complex and the confused physician in practice, sometimes, has started to treat mg/dL (or mmol/L) rather than patients. This confusion has been compounded by debates on the variability of plasma lipid measurements within as well as across laboratories. In the one to one relationship that exists in the physician's office, much of this confusion can be dispelled if, after a thorough clinical evaluation, the patient's situation is taken in context, a diagnosis is made and the indicated therapy is prescribed. A good algorithm is one that focuses first on diagnosis, separates secondary from primary causes of dyslipoproteinemia, starts with diatary therapy, targets drugs to the metabolic disturbance, takes into account the psycho-social environment and the risk factor context and adjusts the treatment according to the observed response. Within this framework, specific target levels may be given due consideration. Treatment should be individualized and the key lipid transport disorders identified. Today, the physician has the advantage of prescribing drugs that have been proven valuable for the ultimate goal of therapy: prevention of atherosclerotic complications.