Histochemical evaluation of placental dipeptidyl peptidase IV (CD26) in pre-eclampsia: enzyme activity in villous trophoblast indicates an enhanced likelihood of gestational hypertensive disorders

Nitric oxide (NO) acts as a modulator of neuronal transmission in mature neuronal systems, including the retina. Recently, NO has also been suggested to have a trophic function during development. We examined immunocytochemically the distribution of NO-producing cells in developing and transplanted rabbit retinas. An antibody detecting the neuronal isoform of its biosynthetic enzyme, nitric oxide synthase (NOS), was used on normal developing retinas [starting at embryonic day (E) 15] and on rabbit retinal transplants after various survival times (1-139 days after surgery). Weakly stained cell bodies were first observed in the proximal margin of the neuroblastic layer at E 29. Stained processes projecting towards a developing inner plexiform layer were also visible at this time point. Immunoreactive cells were located at later stages in the innermost part of the inner nuclear layer and in the ganglion cell layer, and are likely to correspond mainly to amacrine cells. NOS-labelled cells were also found in retinal transplants. The first NOS-labelled cells appeared, as in normal developing retinas, in ages corresponding to E 29 and were still detected in transplants corresponding to postnatal day 123. NOS-labelled cells were seen in areas between rosettes, where amacrine cells are located. NOS-labelled processes were at times seen to project for long distances, forming very distinct plexuses. NOS-containing amacrine cells thus appear both in the transplants and in developing retinas in the embryonic stages, long before synaptic function involving these cells can be expected, suggesting a role for NO not only in neuromodulation but also in retinal development.     

Human papillomavirus as an etiological factor in cervical cancer: significance for health care practice

The migration of substances from rubber packaging materials into drug products can be significant with certain packaging materials in contact with organic solvent systems. Recommendations for testing drug products for leachables are continually evolving to address new developments. Testing packaging materials using simulated solvents is not always an acceptable protocol for the pharmaceutical industry. We describe a rational strategy for evaluation of the drug product for packaging extractables. A profile of the extractables from rubber packaging materials was made with a range of organic solvents and stress conditions to provide information on substances to target in the drug product. The drug product was evaluated to determine if the matrix would cause interferences that might inhibit detection of the found extractables. Analytical methods were selected based on these findings. The procedures were validated according to FDA guidelines. A stability program using time and storage conditions as variables provided information for acceptance criteria. This same strategy can be used on other types of pharmaceuticals and packaging materials.     

Balloon dilatation in acute myocardial infarct in routine clinical practice: results of the register of the Working Society of Leading Cardiologic Hospital Physicians in 4,625 patients

Balloon angioplasty as the treatment of first choice in the setting of an acute myocardial infarction (AMI) is gaining widespread acceptance because of favourable results from specialised centres concerning high patency rates and low mortality. This study reports the results of angioplasty for AMI at large community hospitals during 1992-1995. 4625 procedures were performed at 68 centres of the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhaus?rzte (ALKK). The age of the patients was 60.8 +/- 11.3 years, with 75.1% men. The infarct related artery was the left anterior descendent in 43%, the right coronary artery in 37%, the circumflex artery in 16%, a bypass graft in 2.3% and the left main stem in 1.4% of patients. The success rate (residual stenosis < 50%) of the intervention was 86%. There was a wide range of procedures per centre, with a median of 40 AMI angioplasties per year and centre. The amount of angioplasties for AMI in relation to all angioplasties performed during this period rose from 5.2% in 1992 to 5.9% in 1995 (p = 0.01). Local complications at the puncture site occurred in 3.2%, with the need for a surgical intervention in 1.1% of patients. In 273 (5.9%) of the patients a second angioplasty was performed during the hospital stay. Aortocoronary bypass surgery was performed in 3% of the patients. Hospital mortality was 9.5% (438/4625 patients). The mortality rate remained constant during the years investigated (1992: 10.6%; 1993: 8.6%; 1994: 9.7%; 1995: 9.8%; p = ns). Higher mortality was observed in older patients, patients with multiple vessel disease, the left anterior descending artery or a bypass graft as infarct related artery as well as in patients with failed reperfusion (residual stenoses > 50%). Hospitals with a case load of more than 40 angioplasties for AMI per year showed a lower mortality as compared to the others. In clinical practice at large community hospitals results of angioplasty for AMI concerning mortality, complications and technical success rate are comparable to those of highly specialised centres. The absolute numbers of angioplasties for AMI increased constantly over the years.     

Assessment of cocaine use with quantitative urinalysis and estimation of new uses

Qualitative urinalysis methods of monitoring cocaine use may over-detect frequency of use, possibly decreasing the ability of clinical trials to detect effective treatments. Quantitative urinalysis and newly developed criteria for identifying new cocaine use were evaluated as alternative measures of cocaine use. Urine specimens collected in a cocaine dosing study in non-treatment-seeking subjects (n = 5) and a cocaine treatment trial (n = 37) were analyzed for the cocaine metabolite, benzoylecgonine, with qualitative and quantitative methods. Pharmacokinetic criteria ('New Use' rules) were applied to quantitative data to identify occasions of new cocaine use. Results were compared to known cocaine administrations in the laboratory study and to self-reported drug use and qualitative urinalysis for subjects in the clinical trial. New Use criteria correctly identified cocaine administrations in the cocaine dosing study in all but a small number of specimens. In the clinical trial, quantitative urinalysis and estimated New Uses provided more information about patterns and frequency of use than qualitative urinalysis in the different treatment conditions in the clinical trial. Interpretation of quantitative urinalysis with New Use rules appears to be a useful method for monitoring treatment outcome and may be more accurate than traditional qualitative urinalysis in estimating frequency of cocaine use.     

Hepatitis B virus infection, hepatitis B vaccine, and hepatitis B immune globulin

Hepatitis B virus (HBV) infection is a major health problem in the United States; in 1995, approximately 128,000 cases occurred. Transmission of HBV occurs primarily by blood exchange (eg, by shared needles during injection drug use) and by sexual contact. Persons infected early in life are much more likely to become chronically infected than those infected during adulthood: as many as 90% of infants infected perinatally develop chronic infection and up to 25% will die of HBV-related chronic liver disease as adults. Clinical signs of acute hepatitis occur in about 50% of infected adults but in only 5% of infected preschool-aged children. In the United States, hepatitis B vaccine is currently made by recombinant DNA technology using baker's yeast. Preexposure vaccination results in protective antibody levels in almost all infants and children (> 95%) and healthy adults younger than 40 years of age (> 90%). The most common adverse event following administration of hepatitis B vaccine is pain at the injection site, which occurs in 13% to 29% of adult and 3% to 9% of children. A comprehensive hepatitis B vaccination policy is now recommended that includes (1) routine infant vaccination; (2) catch-up vaccination of 11- to 12-year-olds who were not previously vaccinated; (3) catch-up vaccination of young children at high risk for infection; (4) vaccination of adolescents and adults based on lifestyle or environmental, medical, and occupational situations that place them at risk; and (5) prevention of perinatal HBV infection.     

Transfer of rps19 to the nucleus involves the gain of an RNP-binding motif which may functionally replace RPS13 in Arabidopsis mitochondria

The discovery of disrupted rps19 genes in Arabidopsis mitochondria prompted speculation about the transfer to the nuclear compartment. We here describe the functional gene transfer of rps19 into the nucleus of Arabidopsis. Molecular cloning and sequence analysis of rps19 show that the nuclear gene encodes a long N-terminal extension. Import studies of the precursor protein indicate that only a small part of this extension is cleaved off during import. The larger part of the extension, which shows high similarity to conserved RNA-binding domains of the RNP-CS type, became part of the S19 protein. In the Escherichia coli ribosome S19 forms an RNA-binding complex as heterodimer with S13. By using immuno-analysis and import studies we show that a eubacterial-like S13 protein is absent from Arabidopsis mitochondria, and is not substituted by either a chloroplastic or a cytosolic homologue of this ribosomal protein. We therefore propose that either a highly diverged or missing RPS13 has been functionally replaced by an RNP domain that most likely derived from a glycine-rich RNA-binding protein. These results represent the first case of a functional replacement of a ribosomal protein by a common RNA-binding domain and offer a new view on the flexibility of biological systems in using well-adapted functional domains for different jobs.