Comparison of antihypertensive effects of nicardipine with nitroglycerin for perioperative hypertension

BACKGROUND: To compare the efficacy of intravenous (iv) nicardipine with nitroglycerin for the treatment for patients with perioperative hypertension. METHODS: Forty patients with perioperative hypertension randomly divided into two groups were treated with intravenous calcium entry blocker, nicardipine, or vasodilator, nitroglycerin. Haemodynamic measurements including mean arterial and pulmonary arterial pressure, central venous and pulmonary capillary wedge pressure, and cardiac output were recorded; peripheral and pulmonary vascular resistance were calculated. RESULTS: Both medications were effective in reducing blood pressure and controlling haemodynamics. During the maintenance by continuous iv infusion, nicardipine controlled hypertension more rapidly than nitroglycerin (nicardipine 10.5 +/- 2.5 min and nitroglycerin 18.7 +/- 2.8 min, p < 0.05) without significant alteration in heart rate. The total frequency of dose adjustments required to achieve therapeutic response was significantly less in the nicardipine-treated group (2.5 +/- 0.3 for nicardipine and 6.2 +/- 1.4 for nitroglycerin, p < 0.05). Incidence of hypotensive episodes during the infusion were observed in both groups [nicardipine 5% (1/20) and nitroglycerin 30% (6/20), p < 0.05]. CONCLUSIONS: Intravenous nicardipine is as effective as nitroglycerin in the treatment of perioperative hypertension. Specific advantages have been identified such as stable dose-response effect, less hypotensive and tachycardial effects during the use of iv nicardipine in treatment of hypertensive patients.     

Mutational analysis of the Drosophila sister-chromatid cohesion protein ORD and its role in the maintenance of centromeric cohesion

The ord gene is required for proper segregation of all chromosomes in both male and female Drosophila meiosis. Here we describe the isolation of a null ord allele and examine the consequences of ablating ord function. Cytologically, meiotic sister-chromatid cohesion is severely disrupted in flies lacking ORD protein. Moreover, the frequency of missegregation in genetic tests is consistent with random segregation of chromosomes through both meiotic divisions, suggesting that sister cohesion may be completely abolished. However, only a slight decrease in viability is observed for ord null flies, indicating that ORD function is not essential for cohesion during somatic mitosis. In addition, we do not observe perturbation of germ-line mitotic divisions in flies lacking ORD activity. Our analysis of weaker ord alleles suggests that ORD is required for proper centromeric cohesion after arm cohesion is released at the metaphase I/anaphase I transition. Finally, although meiotic cohesion is abolished in the ord null fly, chromosome loss is not appreciable. Therefore, ORD activity appears to promote centromeric cohesion during meiosis II but is not essential for kinetochore function during anaphase.     

Myocardial infarction and regulatory myosin light chain

Myosin from cardiac muscle consists of two heavy chains and two pairs of light chain. Regulatory myosin light chain (RMLC) is phosphorylated by a Ca2+ and calmodulin dependent myosin light chain kinase. The impact of experimental myocardial infarction on cardiac RMLC was studied. The left anterior descending coronary artery of rabbits was ligated. Three, 7 and 14 days later the animals were euthanized, sections of the heart were frozen in liquid nitrogen and later subjected to 2-dimensional electrophoresis. Isoelectric focusing was carried out at a pH range of 4.5-5.4. Reproducible patterns of protein separation showed four spots with proteins of phosphorylatable regulatory light chains shifted to a more negative pH as compared to essential light chain. We investigated changes in phosphorylation of RMLC in infarcted heart muscle. As compared to sham operated animals, a decline in phosphorylation of RMLC was present in both infarcted and non-infarcted portions of the left ventricle; the latter was significant 7 days following the onset of ischemia. In contrast, the decline in percent phosphorylation in the infarcted area was not significant. The amount of RMLC decreased significantly in the infarcted portion. A highly significant reduction in the percent of viable cardiomyocytes accompanied the decline in phosphorylation. There was a significant correlation of RMLC following administration of isoproterenol, 7 and 14 days following onset of ischemia. Only faint traces of essential atrial myosin light chain (ALC-1) were present in the non-infarcted portion of the left ventricle. No correlation was found between percent phosphorylation and the amount of RMLC (density) following infusion of saline or isoproterenol. Isoproterenol significantly increased percent phosphorylation without altering the amount of RMLC protein. We conclude that myocardial infarction profoundly affects regulatory myosin light chain phosphorylation in the infarcted and non-infarcted areas of the myocardium and that RMLC plays a significant part in myocardial contractility.     

Integrated safety analysis of requirements specifications

This paper describes an integrated approach to safety analysis of software requirements and demonstrates the feasibility and utility of applying the individual techniques and the integrated approach on the requirements specification of a guidance system for a high-speed civil transport being developed at NASA Ames. Each analysis found different types of errors in the specification; thus together the techniques provided a more comprehensive safety analysis than any individual technique. We also discovered that the more the analyst knew about the application and the model, the more successful they were in finding errors. Our findings imply that the most effective safety-analysis tools will assist rather than replace the analyst. A shorter version of this paper appeared in the Proceedings of the 3rd International Symposium on Requirements Engineering, Annapolis, Maryland, January 1997. The research described has been partly funded by NASA/Langley Grant NAG-1-1495, NSF Grant CCR-9396181, and the California PATH Program of the University of California     

Occupational medicine in Canada and Poland in the 1990s

The protocol describes (i) methods for the investigation of neuropeptide catabolism in the central nervous system (CNS), (ii) the identification of the neuropeptidases involved, and (iii) methods for the determination of neuropeptide stability in vitro. These methods are applicable also to study the degradation of peptide hormones by peripheral cells or tissues. To identify peptide degradation products, nanomolar amounts (micromolar concentrations) of peptides are incubated in synthetic media with cell or tissue cultures. Aliquots of the supernatants are withdrawn after different times, peptide fragments separated and fractionated by reversed-phase HPLC, and identified by peptide chemical methods. The peptidases responsible for this degradation can be identified by the use of specific inhibitors listed in the protocol. For receptor binding assays or the study of peptide effects in physiological, nanomolar concentrations the stability of the peptides in an in vitro system should be checked by addition of radiolabeled peptides (femtomolar or nanomolar concentrations) and monitoring the peptide degradation by a procedure analogous to that established for unlabeled peptides. The addition of more or less specific peptidase inhibitors enhances peptide stability in vitro, and thus it can be assured that a given peptide concentration is maintained during biological assays.