Disease gene patents: overcoming unethical constraints on clinical laboratory medicine. (1/154)

The rapidly growing number of disease gene patents--patents that claim all methods for diagnosis of a particular genetic condition--threatens the ability of physicians to provide medical care to their patients. In the past, patented diagnostic tests were made broadly available to the medical community in the form of test kits or licenses to use the patented test. Disease gene tests, however, are being monopolized by a small number of providers. Monopolization of medical testing services: (a) threatens to restrict research activities; (b) creates unacceptable conflicts of interest; (c) may reduce patient access to testing; (d) may lead to inequitable extensions of patent terms on tests and related discoveries; and (e) grants to patent holders the ability to dictate the standard of care for testing, and to otherwise interfere with the practice of medicine. Because of the risks raised by monopolization, amendment of the patent law to require compulsory licensing of physicians providing medical services is recommended.  (+info)

Postmarketing analysis of lovastatin use in the VA Northern California System of Clinics: a retrospective, computer-based study. (2/154)

Prevention of coronary heart disease is a major public health goal. The efficacy of lovastatin in lowering serum cholesterol has been proven in research studies, but its efficacy in practice is unclear. To evaluate our practice patterns and outcome in the Veterans Administration Northern California System of Clinics, we reviewed computer-based records of 203 unselected patients issued lovastatin; 193 (95%) were men, and the average patient age was 66 +/- 9 years. The average daily dose of lovastatin was 24 +/- 10 mg, and average duration of therapy was 22 +/- 11 months. Only 72 patients (35%) were instructed on the prescription to take their medication with the evening meal, and only 59 patients (29%) had seen a dietitian during the observed (1 to 3 years) treatment period. Nevertheless, among the 124 patients with pretreatment lipid data, total serum cholesterol decreased by 18% from 271 +/- 45 to 221 +/- 41 mg/dL (P < 0.001), and low density lipoprotein (LDL)-cholesterol decreased by 23% from 185 +/- 43 to 143 +/- 37 (P < 0.001) mg/dL. High density lipoprotein-cholesterol and triglycerides were unchanged. Of the 168 patients with LDL-cholesterol data during the treatment period, only 74 (44%) achieved an LDL-cholesterol level of less than 130 mg/dL, the minimum goal for a population of older males with a high incidence of other cardiac risk factors. Safety surveillance with liver function testing was performed at least once in 192 patients (95%), but with creatine phosphokinase (CPK) testing in only 123 patients (61%) during the survey period. Enzyme elevations were minor, but occurred at least intermittently in approximately one quarter of patients. Only 5.7% of patients on lovastatin manifested an increase in transaminases on therapy. Due to incomplete baseline data, it is unclear how many patients had elevated CPK as a result of lovastatin. We conclude that: (1) lovastatin is effective in lowering total and LDL-cholesterol in practice, but is often used in dosage insufficient to lower LDL-cholesterol to goal levels; (2) patients are not being adequately educated on dosing schedules; (3) toxicity may be underestimated by infrequent and inconsistent surveillance; and (4) nonpharmacologic therapy is underutilized.  (+info)

Changes in clinical pathology parameters during gestation in the New Zealand white rabbit. (3/154)

Hematology and serum chemistry parameters were analyzed in 2 groups of pregnant rabbits to assess changes in these parameters over the course of gestation. These data were used to generate a historical control reference range for embryofetal development regulatory toxicology studies. During the 28-day gestation period, the following major changes were observed. Red blood cell counts, hemoglobin, and hematocrit increased slightly up to day 13 and subsequently decreased progressively to a nadir for all parameters on day 25. Reticulocyte counts increased maximally by day 16 and then decreased to a minimum value on day 28. White blood cell counts progressively declined after day 7. Platelet counts increased slightly by day 10, were relatively stable until day 13, then progressively decreased to a nadir on day 25. Aspartate aminotransferase and alanine aminotransferease values increased steadily throughout the study to reach a maximum value on day 25. Triglycerides increased to their maximum value by day 19 and then steadily decreased until day 28, whereas cholesterol decreased progressively to reach a nadir on day 25. Urea and total protein decreased steadily from day 13 onward. Calcium values decreased throughout the study to reach a minimum value on day 28. Phosphorus values increased slightly on days 7 and 13 and then progressively decreased to reach a nadir on day 28. With a few exceptions, changes that occur in clinical pathology parameters during pregnancy in the rabbit are similar to those observed in pregnant women. Therefore, the rabbit can be considered a suitable species for embryofetal development toxicity studies with regard to clinical pathology.  (+info)

Evaluation of ready-to-use liquid reagents for clinical chemistry in laboratory animals. (4/154)

We evaluated the ready-to-use liquid reagents for clinical chemistry (6 tests), to assess their suitability for use in the toxicology laboratory setting. Hitachi 736 automated analyzer was used for the analyses. The evaluation included the following studies: Precision, Linearity, Effects of interference substances such as hemolytic hemoglobin, bilirubin, turbidity to the analytical values and correlation to the solid reagents, which are prepared each time they are needed. The precision and linearity data were within the reagents' specifications. Results of comparison of the liquid reagents and the solid reagents in analyzing plasma samples of rats, dogs and monkeys were generally good except for a bias in results for GOT and GPT, regardless of the animal species tested. It is concluded that these types of liquid reagents can be used in clinical pathology examinations in animal studies.  (+info)

Thrombosed dissection of the ascending aorta complicating extravasation. (5/154)

This report presents 2 patients with thrombosed dissection of the ascending aorta complicating extravasation. The first case was an 85-year-old male admitted with shock due to cardiac tamponade. Plain computed tomography (CT) demonstrated a dilated ascending aorta without clear evidence of aortic dissection. The second case was a 77-year-old female presenting with shock, in whom an enhanced CT scan demonstrated a dilated ascending aorta and periaortic effusion. However, dissection of the distal ascending aorta was not identified in either case before emergency surgery. In case 1, soon after the bloody pericardial effusion was decompressed during the operation, bleeding from the ascending aorta occurred. A small intimal tear was found in the distal ascending aorta, and in each case the pseudolumen was filled with fresh thrombus. The ascending aorta was replaced. Each patient had an uneventful postoperative recovery. Based on this experience, it is suggested that patients with thrombosed ascending aortic dissection complicating extravasation should undergo early graft replacement.  (+info)

Causes of unsatisfactory performance in proficiency testing. (6/154)

BACKGROUND: Proficiency testing (PT) provides a measure of the effectiveness of laboratory quality assurance programs. Test reports are released from processes that the laboratory judges to be in conformance with quality specifications; an evaluation of unsatisfactory performance (UNSAT) by a PT provider is an unexpected outcome for the laboratory. An understanding of the root cause(s) of testing errors provides an opportunity for the continuous improvement of laboratory services. METHODS: We used participant data from the New York State Department of Health PT program to characterize the quality of testing in the toxicology specialty. Outcomes from laboratory investigations into causes of UNSAT and information on quality control practices collected from all program participants were used to identify the root causes of error. RESULTS: Two classes of error were encountered: spurious test results caused by lapses in standard operating procedures and instrument malfunctions (300 per million assays) and common-cause analytic error (7000 per million assays or 0.7% rate of UNSAT). Causes of spurious results included inaccurate mathematical correction for specimen dilution, misinterpretation of instrument codes, and instrument sampling errors. Calibration drift was most frequently cited as the common-cause analytic error. Approximately one-half of the laboratories used an allowable error for the quality control of analytical systems that exceeded the threshold error specified by manufacturers for stable instrument performance. CONCLUSIONS: The causes of spurious results suggest the need for ongoing competency testing of analysts where analyst intervention is required in an otherwise automated process, and for continued diligence in mistake-proofing instrument design. The intrinsic quality of laboratory testing is unlikely to improve until the allowable error in quality control is consistent with manufacturer specifications for stable system performance.  (+info)

A new method of quantitative fecal fat microscopy and its correlation with chemically measured fecal fat output. (7/154)

Fecal fat microscopy using the Sudan stain has suffered from a relative lack of specificity, and results are "qualitative." Therefore, we developed a quantitative fecal fat microscopic method with hopes of improving diagnostic accuracy. One hundred eighty patients with chronic diarrhea collected stools for 1 to 3 days, and fecal fat output was measured by a standard chemical method, and microscopy was performed by the old qualitative and new quantitative methods. There was a highly statistically significant linear correlation between quantitative fecal fat microscopy and chemically measured fecal fat output. The quantitative microscopic method had a sensitivity of 94% and a specificity of 95%; the traditional method had a sensitivity and specificity of 76% and 99%, respectively. Fecal fat Sudan microscopy performed by a dedicated approach to counting and size measurement of fat globules can yield a quantitative result that correlates well with chemically measured fecal fat output and has a high diagnostic accuracy.  (+info)

Subchronic and chronic toxicological investigations on metiram: the lack of a carcinogenic response in rodents. (8/154)

Metiram complex is a non-systemically acting fungicide of the group of ethylenebisdithiocarbamates (EBDC). The subchronic and chronic toxicity and the carcinogenic potential of metiram (containing 2% ethylene thiourea, ETU, as an intentionally added impurity) were investigated. Doses in the chronic/carcinogenicity rat study were 0, 5, 20, 80, or 320 ppm. In the carcinogenicity study in mice, diets were administered for 89 weeks (females) or 95 weeks (males) at doses of 0, 100, 300, or 1000 ppm. No oncogenic response was noted in either species. The subchronic studies in rats and mice further investigated the thyroid as a target organ. Doses of 0, 5, 80, 320, or 960 ppm were utilized in the rat study and a NOAEL of 80 ppm was established. In the subchronic mouse study, diets containing 0, 300, 1000, 3000, or 7500 ppm were utilized. A NOAEL of 300 ppm was established in this study. In summary, the findings of these studies defined the toxicity of metiram in rodents and demonstrated the lack of a carcinogenic response following chronic dietary exposure in the rat and mouse. The NOAELs that were established in these studies were consistent with the NOAELs established for thyroid toxicity/carcinogenicity in studies on ethylenethiourea (ETU).  (+info)