Action of calcitonin gene-related peptide upon bovine vascular endothelial and smooth muscle cells grown in isolation and co-culture.

1. Bovine aortic endothelial cells (BAE) and smooth muscle cells (BASM) were grown separately and in co-culture. 2. Calcitonin gene-related peptide (CGRP) caused dose-dependent activation of adenylate cyclase in each cell type when grown in isolation. The concentration of CGRP causing half-maximal activation in BAE and BASM was 200 nM and 310 nM, respectively. 3. In cells grown in co-culture exposure to bradykinin produced dose-dependent elevations in cyclic GMP content which were maximal 1 min after application of the agonist. 4. CGRP (1 nM-1 microM) did not stimulate a rise in cyclic GMP in co-cultures. 5. Displaceable CGRP binding was identified throughout the wall of the bovine aorta. 6. We conclude that CGRP receptors coupled to adenylate cyclase are present on BAE and BASM, but there is no coupling of these receptors to the release of any agent (such as endothelium-derived relaxing factor) that activates guanylate cyclase.     

Bazett and Fridericia QT correction formulas interfere with measurement of drug-induced changes in QT interval.

BACKGROUND: The QT interval on the ECG is prolonged by more than 50 marketed drugs, an effect that has been associated with syncope and/or sudden cardiac death due to an arrhythmia. Because changes in heart rate also change the QT interval, it has become standard practice to use a correction formula, such as the Bazett formula, to normalize the QT interval to a heart rate of 60 bpm, that is, the rate-corrected QT or QTc. Numerous other formulas have been devised to make this correction, including the Fridericia, Hodges, and Framingham formulas. OBJECTIVES: The purpose of this study was to investigate how the Bazett formula and three other formulas influence assessment of the QT-prolonging effect of the potassium channel-blocking drug ibutilide. METHODS: Using a standardized physical activity protocol, the QT interval was assessed over a broad range of heart rates before and after an infusion of ibutilide (4.75 microg/kg) that produced a stable 15- to 20-ms QT prolongation in consenting normal subjects (9 men and 9 women). The QT interval was measured digitally over a range of heart rates from 60 to 120 bpm, and then four correction formulas (Bazett, Fridericia, Framingham, or Hodges) were applied. The uncorrected change in QT interval due to ibutilide was compared with the change using each of the formulas by repeated measures analysis of variance. RESULTS: At heart rates from 60 to 120 bpm, the Bazett and Fridericia correction formulas overestimated the change in QT in both men and women (P <.001). However, the Framingham and Hodges formulas did not alter the accuracy of the assessment of QT interval change. CONCLUSION: Rate correction of QT intervals using the standard Bazett and Fridericia formulas can introduce significant errors in the assessment of drug effects on the QT interval. This has implications for the clinical assessment of drug effects and for the safety assessment of new drugs under development.     

Repair of large midline incisional hernias with polypropylene mesh: Comparison of three operative techniques

Polypropylene mesh is widely used for the reconstruction of incisional hernias that cannot be closed primarily. Several techniques have been advocated to implant the mesh. The objective of this study was to evaluate, retrospectively, early and late results of three different techniques, onlay, inlay, and underlay. The records of 53 consecutive patients with a large midline incisional hernia — 25 women and 28 men, mean age 60.4 (range 28–94) — were reviewed. Polypropylene mesh was implanted using the onlay technique in 13 patients, inlay in 23 patients, and underlay in 17 patients. Either the greater omentum or a polyglactin mesh was interponated between the mesh and the viscera. The records of these 53 patients were reviewed with respect to: size and cause of the hernia, pre- and postoperative mortality and morbidity, with special attention to wound complications. Patients were invited to attend the outpatient clinic at least 12 months after implantation of the mesh for physical examination of the abdominal wall. Postoperative complications occurred in 14 (26.4%) patients. The onlay technique had significantly more complications, as compared to both other techniques. Reherniation occurred in 15 (28.3%) patients. The reherniation rate of the inlay technique was significantly higher than after the underlay technique (44% vs 12%, P=0.03) and tended to be higher than the onlay technique (44% vs 23%, P=0.22). Repair of large midline incisional hernias with the use of a polypropylene mesh carries a high risk of complications and has a high reherniation rate. The underlay technique seems to be the better technique.     

Central nervous system decompression sickness: latency of 1070 human cases

Many aspects of central nervous system (CNS) decompression sickness (DCS) are poorly understood, including the temporal pattern of its presentation and the pathogenic mechanisms involved in the development of the disease. Using case histories and clinical series published in the literature and retrieved from treatment center records, this study is an attempt to define the interval between surfacing from a hyperbaric exposure and the onset of symptoms of CNS DCS. The results of 1070 cases of human CNS DCS were included in the study. The results show that the disease generally occurs rapidly: over 50% became symptomatic within 10 min of returning to 1 ATA, and in only 15% of cases was the onset of symptoms delayed for more than 1 h. Cerebral DCS had a more rapid onset than spinal cord disease: 50% of cerebral cases became apparent within about 3 min and a similar proportion of spinal cord cases within about 9 min from surfacing. The influence of these results on the diagnosis and treatment of dysbaric illness, on the safety of certain diving practices, and on possible pathogenic mechanisms is discussed.     

Ballistocardiogram of avian eggs determined by an electromagnetic induction coil

As an avian embryo grows within a eggshell, the whole egg is moved by embryonic activity and also by the embryonic heartbeat. A technical interest in detecting minute biological movements has prompted the development of techniques and systems to measure the cardiogenic ballistic movement of the egg or ballistocardiogram. (BCG). In this context, there is interest in using an electromagnetic induction coil (solenoid) as another simple sensor to measure the BCG and examining its possibility for BCG measurement. A small permanent magnet is attached tightly to the surface of an incubated egg, and then the egg with the magnet is placed in a solenoid. Preliminary model analysis is made to design a setup of the egg, magnet and solenoid coupling system. Then, simultaneous measurement with a laser displacement measuring system, developed previously, is made for chicken eggs, indicating that the solenoid detects the minute cardiogenic ballistic movements and that the BCG determined is a measure of the velocity of egg movements.