Infectious diseases

Routine antenatal screening can detect some potentially serious infectious diseases or susceptibility to infection and allow intervention to prevent adverse outcomes. However, screening programmes can only be justified if appropriate criteria are met for the quality of laboratory tests and interventions. For many infections that are associated with adverse maternal or fetal effects, there are no suitable, cost-effective methods of screening or prevention. However, early diagnosis of infection in high-risk women or those with symptoms can allow preventive intervention. Acute febrile illness or other symptoms consistent with infection during pregnancy should be investigated more diligently than in a non-pregnant woman. Early diagnosis of an apparently trivial maternal infection may prevent serious fetal disease. When the diagnosis of maternal infection is made, appropriate action depends on the nature of infection and the stage of pregnancy at which it occurs. The results of serological test should be confirmed, preferably by a reference laboratory, by retesting the original specimen(s) and/or testing further specimens, as appropriate. Management decisions generally should be made in consultation with an infectious disease physician or clinical microbiologist with experience of infectious diseases in pregnancy.     

Effects of Induced Vibrations on Early Age Concrete

The purpose of this investigation was to conduct a laboratory test program on how much induced vibrations on concrete during the period between initial set and final set affect the attainable strength of concrete. To achieve this purpose, a laboratory test program was conducted. The laboratory program consisted of casting 144 76?mm by 152?mm (3×6?in.) concrete cylinders and subjecting them to one of two levels of vibration for either 1 or 2?min at five different ages ranging in time from before, during, and after the setting period for the concrete. The levels of vibration correspond to typical frequencies of vibratory soil compactors and the peak particle velocity produced by the compactors. Both compression and splitting tensile tests were performed. The results of the laboratory study indicate that vibratory soil compaction should not be considered a significant hazard to foundation strength as long as the vibrations are within the limits in this study.     

Heparin-induced thrombopenia: significance and difficulties of precise identification of the immunologic mechanism

Heparin-induced thrombocytopenia (HIT) is a drug induced immunohematologic adverse reaction which is a rare but potentially very severe accident. Its diagnosis is important for epidemiologic and drug surveillance studies and in order to decide the most appropriate treatment. Its importance is enhanced since there is no gold standard diagnostic criteria. In clinical practice the diagnosis is based on a group of criteria related to clinical events and laboratory tests. We have established a score based on anamnestic criteria which allowed us to evaluate and compare two different laboratory tests: a platelet aggregation test (PAT) and a test for the detection of heparin dependent antibodies (Heparin Platelet Induced Antibodies or HPIA). The functional test PAT which is commonly used in expert laboratories detects antibodies inducing platelet aggregation in the presence of heparin. The HPIA test more recently developed is an ELISA test which detects antibodies directed at heparin-platelet factor 4 complexes. The relative value of theses two methods for the diagnosis of HIT is not well documented. We have analysed the results of these two tests in 273 consecutive patients with a suspicion of HIT. The results were concordant in 70% of patients. In selecting the patients with the lowest and the highest probability of HIT according to the score, PAT was found a more sensitive and HPIA a more specific test than the other. At low probability PAT is more often positive than HPIA 18% and 9% respectively. No test is 100% reliable, the specificity being limited for both tests since in about 20% of cases one or both tests are negative contrasting with a highly probable HIT. In this last group of patients, PAT was more frequently positive (86%) than HPIA (72%). Both tests are negative in 6% of patients suggesting the existence of presently unknown antigenic targets. Considering a group of 19 patients with a high probability of HIT, we have found antibodies against IL-8 or NAP-2 in only 7 patients. The discrepancy between a HPIA positive and a PAT negative encountered in 8% of patients may be explained by the existence of IgA or IgM immunoglobulins since in contrast to IgG they are unable to promote platelet aggregation via the CD32 platelet membrane receptor. This work suggests than neither test is 100% reliable and that they play a complementary role in the diagnosis of HIT. The potential advantage of using both tests should be confirmed in complementary studies     

Pitfalls in HIV testing. Application and limitations of current tests

Enzyme-linked immunosorbent assay (ELISA) and Western blot assay are the most commonly used laboratory tests for HIV infection. Both detect antibodies to HIV. ELISA results are based on detection of antigen-antibody complexes by using antibodies labeled with an enzyme that produces a color change in the presence of a specific substrate. Currently licensed ELISA tests have greater than 98% sensitivity and specificity for HIV. Western blot analysis detects antibodies to specific HIV antigens and is best used as a confirmatory test. In spite of the high sensitivity and specificity of both tests, false-positive and false-negative results do occur. Physicians should be aware of specific causes of inaccurate results. In individual cases, knowledge of the patient's history and the criteria used by the laboratory performing the test is important.     

Acute articular rheumatism in the child in 1997

Nine cases of rheumatic fever were seen from 1982 to 1996. The diagnosis was based on Jones criteria. Four of eight children had carditis characterized by mitral regurgitation with or without aortic regurgitation and/or atrioventricular conduction disturbances. The outcome was favorable in all the patients who had carditis initially; one of the patients without initial carditis developed permanent cardiac lesions during a recurrence with carditis. In industrialized countries, the incidence of rheumatic fever declined starting early in the XXth century, then dropped sharply after World War II, and is now extraordinarily low (mean annual incidence, 0.5/100,000 schoolage children). In developing countries, by contrast, rheumatic fever was recognized only after World War II and remains endemic (mean annual incidence, 100 to 200/100,000 schoolage children), contributing a substantial proportion of cases of cardiovascular disease. The diagnosis is difficult and rests on clinical grounds since there is no specific laboratory test. Diagnostic delays are potentially serious. Acute attacks should be managed as therapeutic emergencies. Prevention of recurrences rests on long-term antimicrobial therapy. Rheumatic fever is a disease process resulting from an inappropriate immune response to pharyngitis due to a beta-hemolytic group A streptotoccus (BHAS). A low standard of living may be a factor in developing countries but fails to explain the epidemic flares seen in these areas or the residual background incidence in industrialized countries. A role of host-related susceptibility to the disease has not been demonstrated. The type-specific surface M protein, the main factor associated with high virulence, carries a specific epitope on its distal portion. Rheumatogenic strains have been identified; most produce mucoid colonies. At a given point in time, within a given serotype, the virulence of a specific strain increases. Temporal and spatial variations of observed types contribute additional complexity. Adhesion of the organisms is followed by release of streptococcal degradation products that share antigenic determinants with human tissues including the heart, the synovium, and the neurons. The hyaluronate capsule and M protein of the organisms are capable of initiating immune responses; their presentation to CD4+ T-cells results in lymphokine production, an acute phase humoral response, and a cell-mediated response potentially responsible for permanent valvular damage. In France, the standard of care is to prescribe antimicrobial therapy to all patients with pharyngitis or tonsillitis without performing tests to identify the causative agent. The introduction of tests for the rapid recognition in routine clinical practice of BHAS, which account for only 20 to 30% of all cases of pharyngitis and tonsillitis, should allow a more rational approach to the treatment of these infections. Reserving antimicrobial therapy to those patients with BHAS should not result in an increase in the incidence or rheumatic fever.     

User's requests (from a practitioner's perspective)

As a practitioner, I have to rely on outside clinical laboratories and affiliated hospitals to perform laboratory tests. In this abstract, I describe specific problems I have encountered with third-party laboratories, and propose solutions for these problems to optimize use of laboratory tests. BLOOD TESTS: The most frequent problem in ordering blood tests is the lack of detailed information regarding sampling conditions. I often have to call laboratories to check whether the sample should be serum or plasma, what volume is needed, whether the sample should be cooled, etc. I propose that clinical laboratories should provide practitioners' manuals that describe specific sampling information. ULTRASONOGRAPHY: Most laboratories do not keep the data from ultrasonographic tests. The lack of these is most problematic when test results are interpreted differently by laboratories and by practitioners. Retaining the data would also help private laboratories improve the quality of the test by enabling them to compare their interpretations with others'. ANNUAL MEDICAL SCREENING: Even if an abnormal finding is detected at medical screening clinics, the final diagnosis is usually not sent back to the screening facilities. This is highly recommended to establish an official system that mediates the feedback to screening centers. MRI: Due to miscommunication between practitioners and radiologists, the test is sometimes performed inappropriately. A thorough consultation should occur before the test to clarify specific goals for each patient. PATHOLOGICAL TESTS: Interpretation of results is often inconsistent among laboratories. Independent clinical laboratories tend to report results without indicating sample problems, while pathology departments at affiliated hospitals tend to emphasize sample problems instead of diagnosis or suggesting ways to improve sample quality. Mutual communication among laboratories would help standardize the quality of pathological tests.     

Disseminated intravascular coagulation. Objective criteria for diagnosis and management

Current concepts of the cause, pathophysiology, clinical and laboratory diagnosis, and management of fulminant and low-grade DIC have been presented. Considerable attention has been devoted to interrelationships within the hemostasis system. Only by clearly understanding these pathophysiological interrelationships can the clinician and laboratory scientist appreciate the divergent and wide spectrum of often confusing clinical and laboratory findings in patients with DIC. In this discussion, objective clinical and laboratory criteria for a diagnosis of DIC have been delineated, thus eradicating unnecessary confusion and empirical decisions regarding the diagnosis. Many therapeutic decisions to be made are controversial and will remain so until more is published about specific therapeutic modalities and survival patterns. Also, therapy must be highly individualized depending on the nature of DIC, age, cause of DIC, site and severity of hemorrhage or thrombosis, and hemodynamic and other clinical parameters. Also presented are clear criteria for severity of DIC and objective criteria for defining a response to therapy. Also, because it is often difficult for the individual physician to decide when to stop often extensive therapy, objective criteria whereby therapy may be stopped, as continuation is likely fruitless, have been presented as a guideline. Lastly, it should be appreciated that many syndromes that are often organ specific share common pathophysiology with DIC but are typically identified as an independent disease entity, such as hemolytic uremic syndrome, adult shock lung syndrome, eclampsia, and many other isolated organ-specific disorders.     

Spirometry

Spirometry is the most widely used pulmonary function test. It is used for diagnosis and monitoring in a wide variety of obstructive and restrictive disease patterns. Spirometry is the primary measure in determining disability due to pulmonary disease, and is widely applied in the evaluation of bronchodilator response and airway hyperreactivity. A wide variety of spirometry equipment is currently available, from small portable units to large laboratory systems capable of multiple functions. Most spirometers rely heavily on computerization, which makes them easy to use, but require training and experience on the part of the user. Valid spirometry demands equipment that conforms to recommended standards, and performance of the tests to meet criteria for acceptability and reproducibility. Interpretation of spirometry requires attention to these standards and to careful selection of reference values.     

Management of the patient with Beh?et's disease

Beh?et's disease is a vasculitic disorder in which the aetiopathogenetic pathway has not yet been clarified. Many organs and systems may be affected in BD. The causes of the wide-ranged clinical spectrum and the variable severity of involvement, including the kidneys remain to be defined. Beh?et's disease should also be considered in the differential diagnosis of AA amyloidosis as well as vasculitic connective-tissue disorders. Specific laboratory tests for the diagnosis and follow up are needed. Only clarification of the aetiopathogenesis of BD can lead to better treatment options.     

Several parameters of the state of the nervous, immune and endocrine systems in newborn rats exposed to irradiation during the preimplantation period of embryogenesis]

About a decade ago the introduction of predictive testing for Huntington's disease (HD) was an important milestone in medical history. The aim of the present paper concerning predictive DNA-testing for HD is fourfold. First of all it describes the professional challenge of elaborating an adequate test protocol and of permanently using a multidisciplinary approach to deal with predictive test requests. Secondly the paper is aimed at unraveling the factors that play a part in uptake and decision making regarding predictive testing. Hereby the Health Belief Model is used as a framework for understanding differences between tested and untested persons. Thirdly the impact of the test result on psychological well-being is reviewed. Finally this paper assesses the utilisation of prenatal diagnosis after predictive testing for HD and reflects on the psychological and ethical implications of different types of prenatal tests, including preimplantation genetic diagnosis.     

High prevalence of sexually transmitted diseases in women with urinary infections

OBJECTIVE: To determine the prevalence and factors associated with unrecognized sexually transmitted diseases (STDs) in women who had pelvic examinations and were subsequently released from the ED with a sole diagnosis of urinary tract infection (UTI). METHODS: A 3-month retrospective chart review was performed in an urban teaching hospital ED (> 70,000 visits/year). Women aged 12-45 years who had pelvic examinations and were released from the ED with a sole diagnosis of UTI were included. Patient complaints, physical findings, and laboratory results were reviewed. Laboratory evaluations included the complete blood count, urinalysis, urine pregnancy test, and cervical cultures for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas. RESULTS: Of the 94 women who met study criteria, 53% had proven STDs (19% N. gonorrhoeae, 22% C. trachomatis, 33% Trichomonas). There was no difference between the patients with positive and negative tests for STDs with regard to complaints, physical findings, and laboratory results (all p > 0.05). CONCLUSIONS: Women undergoing pelvic examinations who are subsequently released from this urban ED with the diagnosis of UTI have a high (> 50%) prevalence of occult STDs. No complaint, physical finding, or laboratory result reviewed was associated with the risk of an STD. Consideration should be given to empirical antibiotic therapy in similar urban populations.     

Brief report: a longitudinal examination of the communicative gestures deficit in young children with autism

OBJECTIVES: To provide Canadian physicians with a standard definition of hypertension in pregnancy, recommendations for laboratory investigations and tests for the assessment and management of hypertensive disorders in pregnancy, and a classification of such disorders. OPTIONS: To improve or not improve Canadian uniformity and standardization in the investigation and classification of hypertensive disorders in pregnancy. OUTCOMES: 1) Accuracy, reliability and practicality of diagnostic clinical criteria for hypertensive disorders in pregnancy. 2) Laboratory tests useful to determine severity and prognosis of disorders as measured by maternal and neonatal adverse outcomes. 3) A classification of disorders for use by Canadian physicians to facilitate uniformity and diffusion of research through a common language. EVIDENCE: Articles on hypertensive disorders in pregnancy published from 1966 to 1996, retrieved through MEDLINE search, related to definitions, tests, diagnostic criteria and classification, as well as documents on diagnosis and classification from authorities in the United States, Europe and Australia and from special interest groups. VALUES: High priority was given to the principle of preventing adverse maternal and neonatal outcomes through the provision of diagnostic criteria for severity and prognosis and through dissemination of reliable and pertinent information and research results using a common language. BENEFITS, HARMS AND COST: Higher degree of vigilance in diagnosing hypertensive disorders in pregnancy, allowing for earlier assessment and intervention, and more efficient dissemination of comparative information through common language. No harm or added cost is perceived at this time. RECOMMENDATIONS: (1) A diastolic blood pressure of 90 mm Hg or more should be the criterion for a diagnosis of hypertension in pregnancy and should trigger investigation and management. Except for very high diastolic readings (110 mm Hg or more), all diastolic readings of 90 mm Hg or more should be confirmed after 4 hours. (2) A regularly calibrated mercury sphygmomanometer, with an appropriate-sized cuff, is the instrument of choice. A rest period of 10 minutes should be allowed before taking the blood pressure. The woman should be sitting upright and the cuff positioned at the level of the heart. (3) Both Korotkoff phase IV and V sounds should be recorded, but the phase IV sound should be used for initiating clinical investigation and management. (4) A urine protein level of more than 0.3 g/d should be the criterion for a diagnosis of proteinuria; 24-hour urine collection should be the standard method for determining proteinuria. (5) Edema and weight gain should not be used as diagnostic criteria. (6) Hypertensive disorders diagnosed during pregnancy should be classified as pre-existing hypertension; gestational hypertension with or without proteinuria; pre-existing hypertension with superimposed gestational hypertension with proteinuria; and unclassifiable antenatally but final classification 42 days after delivery. VALIDATION: Except for expert opinions and reviews solicited for this project, these recommendations need to be field tested and validated in Canada. Guidelines endorsed by the Canadian Hypertension Society and the Society of Obstetricians and Gynaecologists of Canada.     

Early syphilis

Given the transmission of Treponema pallidum during human sexual contact, syphilis now occurs in France only in sexually high-risk, disadvantaged populations. The English-language terminology of "early syphilis" has progressively replaced that of "primary" and "secondary" in French usage. Induration of the chancre and the papular nature of secondary skin rashes remain the best criteria for clinical diagnosis. Serological tests associate test specific for treponematoses (Treponema pallidum haemagglutination assay, TPHA) and a nonspecific screening test (Venereal diseases research laboratory, VDRL) to confirm clinically suspected disease. Routine use of long-acting penicillin (benzathine penicillin) is consistently effective. The continuing risk of active syphilis in a pregnant woman and the possibility of severe syphilis in HIV patients require vigilance.     

The millennium criteria for the diagnosis of atopic dermatitis

Atopic dermatitis forms an active area of basic and clinical research, where important new knowledge about genetics and immunopathogenesis has surfaced over the past years, and where simultaneous development of new and innovative therapies is under way. However, the inclusion of any patient in an atopic dermatitis study, whether it is on its genetics, pathogenesis or therapy, requires a diagnosis which is irrefutable. Since there is no simple and also no complicated laboratory procedure to reach a diagnosis of atopic dermatitis, different sets of clinical criteria have been developed for the purpose of making the diagnosis uniformly in different studies as well as in different study centers. The most commonly used are Hanifin and Rajka's set of diagnostic features, which have major and minor clinical criteria to be fulfilled in order to establish a diagnosis of atopic dermatitis. Recent developments in the immunology of atopy have clearly established the major abnormality in this syndrome, the preferential production of allergen-specific IgE. In this contribution, it is suggested that the presence of such antibodies in a given patient should be a mandatory criterium for the diagnosis of atopic dermatitis. Such a diagnostic test however establishes a diagnosis of atopic syndrome, not atopic dermatitis. Thus, for atopic dermatitis we have to rely, for the time being, on additional clinical criteria. The clinical features described in the literature are critically evaluated, and it is suggested that in addition to the mandatory presence of allergen-specific IgE, 2 of 3 principal criteria (pruritus, typical morphology and distribution, chronic or chronically relapsing) should be present for such a diagnosis. Finally, the minor features originally described by Hanifin and Rajka and later evaluated by others are revised and divided over 4 subcategories; a) related to subclinical eczema; b) related to dry skin; c) extra skin folds; and d) ophthalmological pathology. They are suggested to be used as additional criteria only, needed when clinical suspicion is high but the new mandatory and principal diagnostic criteria described here are inconclusive. For study purposes, we suggest that the mandatory and principal criteria are sufficient. They are now evaluated and validated in ongoing atopic dermatitis treatment studies.     

Relevance of nucleic acid amplification techniques for diagnosis of respiratory tract infections in the clinical laboratory

Clinical laboratories are increasingly receiving requests to perform nucleic acid amplification tests for the detection of a wide variety of infectious agents. In this paper, the efficiency of nucleic acid amplification techniques for the diagnosis of respiratory tract infections is reviewed. In general, these techniques should be applied only for the detection of microorganisms for which available diagnostic techniques are markedly insensitive or nonexistent or when turnaround times for existing tests (e.g., viral culture) are much longer than those expected with amplification. This is the case for rhinoviruses, coronaviruses, and hantaviruses causing a pulmonary syndrome, Bordetella pertussis, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Coxiella burnetii. For Legionella spp. and fungi, contamination originating from the environment is a limiting factor in interpretation of results, as is the difficulty in differentiating colonization and infection. Detection of these agents in urine or blood by amplification techniques remains to be evaluated. In the clinical setting, there is no need for molecular diagnostic tests for the diagnosis of Pneumocystis carinii. At present, amplification methods for Mycobacterium tuberculosis cannot replace the classical diagnostic techniques, due to their lack of sensitivity and the absence of specific internal controls for the detection of inhibitors of the reaction. Also, the results of interlaboratory comparisons are unsatisfactory. Furthermore, isolates are needed for susceptibility studies. Additional work remains to be done on sample preparation methods, comparison between different amplification methods, and analysis of results. The techniques can be useful for the rapid identification of M. tuberculosis in particular circumstances, as well as the rapid detection of most rifampin-resistant isolates. The introduction of diagnostic amplification techniques into a clinical laboratory implies a level of proficiency for excluding false-positive and false-negative results.     

Case management study: polyarthritis with fever

In most cases, a thorough initial evaluation will reveal the cause of fever and polyarthritis. However, in some patients the initial diagnosis may be unclear and, as time passes, the characteristic clinical patterns emerge. Recurrent attacks are suggestive of other conditions such as crystal-induced arthritis, Lyme disease, and Mediterranean fever. In rheumatoid arthritis and Reiter's syndrome, the fever resolves and the articular findings predominate with the passage of time. Similarly, Still's disease is initially diagnosed on the basis of clinical criteria, and later confirmed by the evolution of chronic polyarthritis. Diagnostic approaches for the evaluation of patients presenting with acute arthritis have been published and are readily available (2,8,9). The most reliable way to establish the diagnosis for a rheumatic disease is thoughtful and thorough evaluation by an experienced clinician (3,10). Certain discriminating features and confirmatory tests can aid in the diagnosis of polyarthritis with fever (Tables 2 and 3).     

The erythrocyte sedimentation rate. Still a helpful test when used judiciously

ESR is a time-honored, simple, inexpensive test, but unfortunately it lacks sensitivity and specificity. Clinicians need to be aware of appropriate uses, because any test is expensive when ordered often, and evaluation of false-positive results may incur substantial costs and place the patient at risk from additional procedures. ESR should not be used to screen asymptomatic persons for disease. If an increased ESR is encountered and no explanation is immediately apparent, clinicians should repeat the test in several months rather than pursue an exhaustive search for occult disease. ESR may be useful in establishing a "sickness index" in elderly persons who have nonspecific changes in health status and a moderate probability of underlying disease; in screening for infection in specific settings (e.g., orthopedic surgery, pediatrics, gynecology); in diagnosing and monitoring temporal arteritis, polymyalgia rheumatica, and possibly other rheumatic diseases; in monitoring patients with treated Hodgkin's disease; and in assessing iron deficiency in anemia of chronic disease (when correlated with serum ferritin level). An ESR value exceeding 100 mm/hr has a 90% predictive value for serious underlying disease, most often infection, collagen vascular disease, or metastatic tumor. In asymptomatic persons with a markedly elevated ESR value, a minimal number of tests usually reveal the cause.     

Medical legal aspects of clinical monitoring

Modern laboratory technology has spawned a plethora of techniques for measuring and monitoring drug concentrations and body constituents; but the availability and frequent over-use of these determinations, some of which are exotic and require specialized personnel and expensive apparatus have further escalated the already high cost of medical care in several ways. The specter of medical malpractice suits has compelled the physician to practice defensive medicine including ordering unnecessary monitoring procedures, particularly for drug levels. Further impetus has been superadded by the courts and state legislatures; for example, phenylketonuria (PKU) determinations are mandatory in almost all states. Court rulings have held that "common knowledge" not expert testimony, may be all that is necessary to hold the doctor culpable for not ordering a test; nor is expert testimony necessarily required if the Physicians Desk Reference (PDR) or drug company insert recommends that certain tests or monitoring procedures be performed and the doctor fails to comply. (PSRO) programs will force further conformity, leave less to the discretion of the physician and place the government in an ever more regulatory role. Professional societies should take cognizance of the impropriety and danger of the government dictating diagnosis and treatment and should launch a vigorous program to scrutinize pending regulatory legislation and to make official and informed representations to appropriate legislators.     

Prevalence and predictors of work related respiratory symptoms in workers exposed to organic dusts

Treatment of initial caries, albeit an everyday occurrence for the dental practitioner, presents considerable demands of patient assessment and diagnosis. Whatever decisions are made--to restore caries or to attempt to arrest its progress--the adoption of a maintenance program is of paramount importance. Patient motivation, in respect to dietary control and satisfactory oral hygiene, is central to a successful outcome, and in the future, practice management programs may include RAC as a diagnostic aid. New methods of caries management are more dynamic than traditional methods and place restoration of the lesion toward the bottom of the list of possible treatments, with the biologic rather than the mechanistic approach being a priority. However, the teaching of RAC in dental schools and the third-party funding of diagnostic tests and diagnosis are also required to reflect the increasing complexity of management of initial caries. If restorative intervention is indicated following diagnosis and RAC, treatment of initial caries should involve a minimal-intervention adhesive technique.     

A computerized approach to statistical quality control for radioimmunoassays in the clinical chemistry laboratory

Methods for statistical quality control for the clinical laboratory in general, and radioimmunoassay in particular, have been proposed for many years. Unfortunately, only a very small number of laboratories have adapted these procedures. By use of teletypes and other remote terminals, it is possible for all laboratories to access centralized computers where a general purpose quality control program can be stored. This relieves each laboratory of the costly task of developing software, provides some degree of inter-laboratory standardization and facilitates comparison of precision and accuracy between laboratories. A prototype program for this purpose is described. This program evaluates within-assay and between-assay variability, by means of an analysis of variance for a one-way classification random-effects model, and can monitor any assay parameter by use of control chart techniques. In addition, several tests are provided to evaluate the temporal stability of the assay system, and appropriate tests for outliers are included. Also, methods are described for combination of information from several quality control samples. This provides a valid basis for adjustment of assay results or for outright rejection of an assay. For convenience, this program is designed for output on a teletype or similar terminal located in the laboratory. Simplified versions of this program can be readily adapted to desk-top calculators. The original purpose for developing this system was to provide the clinical laboratory with a simple, general, and flexible method for assessing the performance of radioimmunoassays, but its usefulness should extend to virtually all assay methods.