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Biomedical subjects

J H Keffer

Publications and source records attributed to J H Keffer.

At least 19 recordsLinked to original sources

The cardiac profile and proposed practice guideline for acute ischemic heart disease.

Presented with an ever-increasing array of potential tests of myocardial injury, the clinical pathologist in conjunction with physicians in primary care, cardiology, and other clinical disciplines must evolve a practical approach for each individual institution. This involves identifying the tests available for immediate (stat) or timed performance, the appropriate patients for whom testing is desired, the schedule of frequency and duration of testing, and the manner in which the test results are to be interpreted. A guideline is presented to address these issues with the purpose of stimulating local adoption of an appropriately modified version to accommodate the current state of the art. Selective choice of an early marker, creatine kinase MB by mass immunoassay, in conjunction with cardiac troponin I (cTnI), is proposed as the appropriate combination of laboratory tests that emphasizes the cardiospecificity of cTnI for the variety of applications in which the "cardiac profile" formerly has been used, including the spectrum of clinical settings in which suspected myocardial infarction must be considered. A rationale is provided with emphasis on the relative merit of the various biochemical markers in contrast with other modalities for evaluating suspected myocardial injury.

Acute Disease

Endocrinopathy and ectopic hormones in malignancy.

This article reports progress in the field of endocrinopathies and focuses on the molecular aspects of these diseases. Implications for genetics and metabolic study are presented. Although limitations of earlier approaches are confirmed, progress is noted, particularly with regard to the contribution of octreotide scintigraphy. Integrated with the evolving applications of molecular insights, significant clinical progress has been recorded.

Endocrine System Diseases

Myocardial markers of injury. Evolution and insights.

Knowledge of the pathophysiology of ischemic heart disease has advanced in parallel with awareness of the significant limitations inherent in clinical assessment. Biochemical assays, long established as the most reliable means of detecting myocardial injury, have improved significantly. Creatine kinase MB, now optimally measured by the newer mass monoclonal antibody assays, and also measurement of the cardiac troponins objectively identify adverse prognosis. Cardiac troponin I appears to have significant advantages over other markers and may become the assay of choice. This is attributable to the confirmation of cardiospecificity claims regarding this marker. These assays permit increased appreciation of the continuous spectrum of ischemic myocardial injury, earlier diagnosis, refinement of the clinical assessment of risk, and evaluation of alternative treatment regimens. Reassessment of the incorporation of biochemical indicators for thrombolytic therapy can be anticipated. This paper integrates the clinical and biochemical literature in reviewing these concepts.

Biomarkers

Comparison of cardiac troponin I and lactate dehydrogenase isoenzymes for the late diagnosis of myocardial injury.

Cardiac troponin I (cTnI) is a highly specific marker that is elevated in the blood for several days following myocardial infarction. The lactate dehydrogenase (LD) isoenzyme 1 to isoenzyme 2 ratio (LD1/LD2) is the established marker for the late diagnosis of myocardial infarction. In this study, the sensitivity of cardiac troponin I (cTnI) and LD1/LD2 were compared as late markers of myocardial injury over a 5-day period in 36 patients admitted with a diagnosis of myocardial infarction to the coronary care unit. Over this period, the sensitivity of cTnI was significantly greater than that of LD1/LD2 (P < .05). The concurrent elevation of both cardiac markers of the five day period range from 53.1% to 79.4%. However, this low concordance was largely due to an LD1/LD2 < 1 in the presence of an increased cTnI. The average discordance over the 5-day period was 29.5%. Because cardiac troponin I (cTnI) has greater sensitivity than lactate dehydrogenase isoenzymes for delayed diagnosis of myocardial injury and is a more cost-effective test, the authors recommend it as a test of choice in this setting.

Adult

Preanalytical considerations in testing thyroid function.

Remarkable technical advances have permitted analytical measurement of thyrotropin (TSH) and estimates of free thyroxine (FT4) with precision, accuracy, and favorable economics. Combined with an increased appreciation of the key insights into the pituitary-thyroid relation, preanalytical considerations infrequently introduce confounding variables. In reviewing thyroid data, preanalytical considerations include physiological and specimen-based issues. Central to the improvement in thyroid assessment is the recognition that physiological individuals maintain their FT4 within narrow limits. When this deviates, there is a logarithmic response of the TSH concentration to the arithmetic shift in FT4. In effect, the TSH deviation magnifies the subtle shift in FT4. Artifact and other nonthyroid-related preanalytical considerations are infrequently the cause of nonconcordance when discrepancy occurs between the reported values for FT4 and TSH. When abnormalities of TSH and FT4 are encountered, the probability strongly favors a disease state rather than a preanalytical variable. Infrequent but real extrathyroidal pathophysiological states are increasingly recognized as a result of the reliable assessment of the pituitary-thyroid relation.

Humans

Effects of cocaine on anterior pituitary and gonadal hormones.

Acute and chronic cocaine administration has been reported to change endocrine and neurochemical functions in animals and human drug abusers. This study examined the effects of acute cocaine administration on anterior pituitary and gonadal hormones in male human volunteers without a history of drug abuse. Using a double-blind, randomized study design, luteinizing hormone, follicle-stimulating hormone (FSH), prolactin and testosterone levels were measured in 12 healthy men before and after intranasal administration of 2 mg/kg cocaine or placebo. Each subject was studied twice, serving as his own control. Compared to placebo, both luteinizing hormone, and, to a lesser degree, follicle-stimulating hormone levels increased significantly after cocaine, reaching a peak value 60 min after the administration of the study drug. This pattern is consistent with a possible cocaine induced rise in gonadotropin-releasing hormone and subsequent rise in luteinizing hormone and follicle-stimulating hormone due to stimulation of gonadotroph cells in the pituitary gland. Neither cocaine nor placebo induced a change in testosterone levels. Prolactin levels showed a decrease from base line after both placebo and cocaine administration, with a significantly more pronounced decrease after cocaine. This likely reflects the combination of the physiologic diurnal variation in prolactin secretion and an added inhibitory effect on prolactin due to cocaine. These findings show that the acute administration of cocaine significantly alters anterior pituitary hormonal release patterns.

Administration, Intranasal

False-positive serum prostate-specific antigen values in a patient with non-Hodgkin lymphoma of the kidney.

Prostate-specific antigen (PSA) is the clinically most useful tumor marker for prostate cancer. Although false-positive elevations have been reported due to disease processes outside the prostate gland with the use of the polyclonal assay, such false-positive test results have been exceedingly rare with the use of the monoclonal assay. We report the case of a patient diagnosed with a B-cell lymphoma of the kidney and a significant elevation of serum PSA levels by monoclonal assay in the absence of either inflammatory or malignant prostate disease. PSA returned to normal during lymphoma-specific chemotherapy with a cyclophosphamide, mechlorethamine, vincristine, procarbazine, prednisone regimen. Possible explanations and clinical implications are discussed.

Antineoplastic Combined Chemotherapy Protocols

Effects of cocaine on cortisol secretion in humans.

The effects of acute cocaine administration on the pituitary adrenal axis in humans without a history of drug abuse are unknown. The authors studied 12 male volunteers twice in a double-blinded, placebo-controlled, randomized fashion. After intranasal administration of 2 mg/kg cocaine, cortisol levels were significantly higher than after placebo administration. The authors concluded that acute administration of cocaine to humans increases cortisol secretion.

Administration, Intranasal

Economic considerations of point-of-care testing.

Point-of-care testing is a rapidly expanding trend. This review discusses some of the issues driving the development of this new approach to laboratory testing, assesses the factors appropriate in introducing and managing point-of-care testing, and directs attention to realistically assessing the potential for cost-effectiveness analysis. Although considered optimal, formal cost-effective analysis is limited. A commentary on the published literature of the field is presented. Observations are offered on the inadequacies of published studies that purport to describe this application. As an alternative, a more general assessment of the economic effect of point-of-care testing in the general context of the laboratory mission is recommended. Suggested guidelines are included.

Cost-Benefit Analysis

Quality assurance in home laboratory testing.

In review, one is compelled to the notion that a variety of the aforementioned thoughts become pre-eminent in assuring quality. The selection of the tests available for home testing is crucial. They should be divided into categories of single encounter tests and multiple use tests. The single encounter implies a test that has an extremely high degree of reliability and is likely to achieve an answer to the question asked. This should relate to a disease or process for which potential favorable treatment can be achieved or which may have a major favorable impact on public health. In this category one thinks in terms of the worldwide prevalence of hepatitis B and other infectious diseases that are particularly common in third world countries. Yet, these are not "markets" likely to be able to afford this testing. Similarly, these societies are not currently sophisticated in terms of application of preventive measures. On the other hand, major benefits could be projected from the other category of testing, namely, therapeutic monitoring in the hands of individuals who will repetitively test for the same substance in the same manner. This includes not only diabetes but other conditions that are monitored for drug therapy, including seizure disorders and bronchospasm. Inherent in this aspect is the requirement for meaningful and ongoing instruction in proper testing methodology and recording of results. The incorporation of some type of memory device to enforce this aspect of testing appears extremely desirable, if not mandatory. Finally, we must consider the potential for misuse of the single test type of device. One suspects that it would be highly desirable that any test made available for self-testing should also be mandated as accessible through certified laboratories at the request of an individual, which would at least provide reliable performance of the test with a quality result. The development of the concept of quality assurance in home testing is in its infancy and will require continuing evolution.

Aged

Thyroid replacement therapy: a rational approach to laboratory monitoring.

A brief summary of the diagnostic laboratory criteria for primary hypothyroidism and the practical aspects of the pharmacology of thyroid hormone therapy are presented. A minimal testing protocol for the adequacy of replacement therapy is advocated based on classic studies of restored thyroid function.

Humans