Functional abnormalities of experimental autogenous vein graft neoendothelium.

When a vein is grafted into the arterial circulation, the endothelium of the graft is damaged. Regeneration of an intact neoendothelium occurs, but the functional properties of this surface have not been clarified. In this study, the functional integrity of the neoendothelium of veins grafted into the carotid artery of the rabbit was assessed through the use of acetylcholine and histamine to stimulate the production of the important endothelium-derived relaxing factor (EDRF). Control veins, precontracted with norepinephrine [10(-5) M], relaxed after exposure to acetylcholine [( 10(-7) M], 42.4% +/- 6.4%, p = 0.008) and histamine [( 10(-6) M], 30.6% +/- 4.3%, p = 0.03). This relaxation response was abolished after mechanical removal of the endothelium. By contrast, neither acetylcholine nor histamine caused an endothelium-dependent relaxation in the vein grafts, even though scanning electron microscopy demonstrated the presence of a morphologically intact endothelium. However, addition of stabilized EDRF purified from cultured endothelial cells induced relaxation of the vein grafts (35.8% +/- 3.6%, p = 0.002). These data indicate that vein graft endothelium is unable to produce EDRF in response to exposure to acetylcholine or histamine. The inability to produce this potent smooth muscle cell relaxing factor and anti-aggregatory substance may be a predisposition to vein graft failure.     

Regional differences in oesophageal motor function

Abstract  We tested the hypotheses that oesophageal bolus transit and motor function vary regionally, with bolus viscosity and with body position. In healthy volunteers, we measured the bolus head advance time, bolus presence time and bolus transit time in the proximal and distal oesophagus using water and viscous materials. We compared concurrent manometric responses. Bolus head advance time, bolus presence time and bolus transit time were longer in the distal oesophagus during water and viscous swallows in the upright and supine positions. The total bolus head advance time and transit time, measured across the entire oesophageal body, were shorter for water than viscous swallows. The amplitudes of peristaltic pressure waves were lower for viscous swallows, and varied as a function of region. These studies demonstrated true functional differences between the proximal and distal oesophagus using multichannel intraluminal impedance and that the viscosity of the bolus is a determinant of oesophageal function.     

Meniscal suture: a simple method

A simple technique of meniscal suture is described. It avoids the main problem with most other outside-to-inside suture techniques, which is that knots either have to be left inside the joint or have to be pulled out through the meniscus. These knots often come undone or damage either the joint surface or meniscus. Essentially, a suture is inserted from outside to inside through the meniscus, using a cannulated needle. The end of this suture is then pulled back out through a separate hole in the meniscus, using a suture loop inserted with another cannulated needle. The two ends of the first suture are then tied together.     

General practitioners'' views on continuing medical education.

BACKGROUND. The 1990 contract for general practitioners altered the provision of continuing medical education. AIM. This study set out to examine doctors' experiences of postgraduate education before and after the contract and their preferences for the provision of postgraduate education. METHOD. In 1991 a structured questionnaire was sent to 1959 doctors registered on the database held by the west of Scotland postgraduate office. RESULTS. An 82% response rate was obtained. Eighty eight questionnaires had to be excluded. Of 1523 respondents, 74% were entitled to study leave under the terms of their practice agreement, an increase of 15% since the introduction of the contract. When attending courses 11% reported that they always employed a locum (32% occasionally). Those who did so were more likely to be general practitioners in rural areas than in urban or mixed areas. Almost all respondents (1485, 98%) had participated in postgraduate education since April 1990. Lectures remained popular (47% of respondents indicated it was their preferred or most preferred choice) while distance learning and practice based learning were least preferred. Evening meetings and afternoon meetings were the most popular, and Wednesday and Thursday were reported to be the most suitable days for educational meetings. CONCLUSION. Organizing education for a large number of people is difficult, but individuals' preferences and difficulties have emerged which must be taken into account when doing so. In terms of attendance, postgraduate education seems to have been a success although its value in influencing quality of care is more doubtful. Perhaps the development of personal education plans may make learning more useful and relevant.     

Source of raised serum estrogens in male rats with portal bypass.

We sought to establish the mechanism for the raised serum estrogen levels that occur in male rats with portal hypertension and resultant portal bypass. Using the portal vein ligated (PVL) rat model, we evaluated plasma steroid hormone concentrations, metabolic clearance rate (MCR) of estradiol, and hepatic metabolism of androstenedione to estrogens and other products. In contrast to serum testosterone levels that were reduced, serum androstenedione levels were normal in the PVL rat. Estradiol MCR was measured by a constant intravenous infusion technique and was found to be similar in PVL and control animals. Androstenedione MCR was determined during constant intravenous infusion of [3H]androstenedione, and the resultant radiolabeled steroids present in plasma were separated by thin layer chromatography. The MCR of androstenedione was not diminished in PVL rats compared with controls. However, there was a sevenfold increase in the plasma estradiol derived from [3H]androstenedione in rats with portal bypass. Examination of radiolabel excreted in bile during infusion of [3H]androstenedione showed that 25-46% of this steroid was converted to estradiol in PVL rats compared with less than 3% in control male rats (P less than 0.001). Moreover, there was a selective reduction in the excretion of 16 alpha-hydroxyandrostenedione, a finding which suggested that the metabolism of androstenedione via this pathway was decreased. Androstenedione 16 alpha-hydroxylation is known to be catalyzed by a male-specific cytochrome P-450 isoform, P-450UT-A. We conclude that raised plasma estradiol levels after portal bypass in male rats are due to increased production rates, resulting in turn from enhanced aromatization of androstenedione to estradiol. On the basis of the observed specific changes in androstenedione hydroxylation pathways, it is proposed that alterations in levels of sex-specific forms of cytochrome P-450 occur in male rats with portal bypass and could account for the enhanced formation of estradiol.     

Fiber Matrix Descriptors from Permeability Data Without Requiring Membrane Thickness: Theory,Results, and Optimization

Objective: Permeability of basement membrane and all other barriers contains a term for membrane thickness (Δx). This naturally leads to development of methods for measuring Δx that are imprecise, inaccurate, expensive, subject to preparation artifact, and inattentive to variability. Although height and shape of permeability (P) vs. probe radius (α) curves are sensitive to Δx, ln(P) or ln(P/free diffusivity or D_o) curves have shapes independent of Δx. It should, thus, be possible using such characteristics to determine fiber radius (r_f) and void volume ratio (ε) without Δx. We developed such a method to derive membrane structure by the standard model of Ogston and present its experimental evaluation. Methods: Basement membranes were self-assembled using 1: 1 Matrigel: 0.01 M Tris/150 mM NaCl/1.0 mM CaCl₂ buffer on 0.4-μ polycarbonate supports with transport measured in diffusion chambers using FITC-labeled hydroxyethyl starch probes from 25 to 102 Å in radius. Sampling was at 0.5 hr and then for each hour up to 5. Other membranes were measured 7 days after formation. Results: The best fit of the new technique occurred at 3 hr with R² = 0.949 ± 0.003 SEM, r_f = 36.8 ± 2.4 Å, and ε = 0.87 ± 0.02. Membranes studied for 7 days showed more variability but essentially the same characteristics. Conclusions: Membrane thickness is not necessary to reduce permeability of basement membrane to structure, and optimum sampling time is 3 hr.