Addition of sulfonylurea to insulin treatment in poorly controlled type II diabetes. A double-blind, randomized clinical trial

This study examined the potential beneficial effects of the addition of a second-generation sulfonylurea to insulin therapy for poorly controlled type II diabetes. A randomized, double-blind, crossover experimental design was utilized in 16 type II diabetic patients for a period of eight months. Treatment with glyburide, 20 mg/d (plus insulin), compared with placebo (plus insulin) resulted in a significant reduction in mean basal glucose (232 +/- 12 vs 262 +/- 11 mg/dL [12.8 vs 14.4 mmol/L]) and hemoglobin A1C (10.2% +/- 0.5% vs 10.9% +/- 03%) concentrations. Concomitant with this change, basal C-peptide and free insulin values increased with glyburide therapy, but this pharmacological agent did not alter the ability of the patient's erythrocytes to bind insulin. We conclude that in type II diabetic subjects receiving more than 28 units of insulin per day, the addition of glyburide results in a marginal, but statistically significant improvement in basal glucose concentration, but not in glucose tolerance as assessed by integrated glucose concentration. Whether this small improvement in glycemia is worth the additional cost of sulfonylureas or the risk of drug side effects is not known.     

Long microvenous allografts in rabbit femoral arteries and veins

In this study the patency of long microvenous allografts in rabbits with and without immunosuppressive drug therapy was investigated. Eighty-two microvenous autografts (controls) and allografts were transplanted into rabbit femoral vessels. Veno-venous autograft controls were 100% patent at 3 weeks. Rejection of non-immunosuppressed veno-venous allografts consistently produced occlusion between 15-20 days. Thrombus filled the lumen, and a leucocyte invasion destroyed the graft wall. In contrast vein allografts into arteries were 100% patent at 3 weeks; this was reduced to 50% at 4 weeks. Low (5 mg/kg/day) and high (20 mg/kg/day) doses of hydrocortisone over 21 days improved the 3 week patency in veno-venous allografts to 28.5% and 57.0% respectively. Cyclosporin A (15 mg/kg/day) over 8 or 22 days significantly increased the patency rate of veno-venous allografts to 100%. Only cyclosporin A treated rabbits maintained allografts of normal vein morphology to 3 weeks.     

Reconstruction of mandibular defects with metallic prostheses and microvascular jejunal autografts: an experimental study

A study was undertaken to determine the adequacy of vascularised jejunum to provide stable mucosal cover over a non-biological mandibular substitute. Employing a canine model, composite intra-oral bone-mucosal defects were created and reconstructed with a metal plate covered by a microvascular jejunal patch. These were followed for six months and were assessed clinically, histologically and radiologically. Rapid mucosal healing occurred in all cases. The autografts conformed to the contour of the prosthesis and adequate tongue mobility was preserved. All mandibles remained stable throughout the follow-up period. Histologically, short villi covered the jejunal grafts to three months whilst at six months both normal and abnormal jejunal mucosal morphology was evident.     

The significance of resection length on the patency rate, and the histopathology, of experimentally avulsed and microsurgically repaired blood vessels

The significance of resection length on patency rate, and the histopathology, of microsurgically repaired avulsed blood vessels was examined at 3 weeks in two groups of experimentally avulsed rabbit femoral arteries repaired by different surgeons and in a single series of avulsed and repaired veins. All veins were patent 3 weeks after avulsion and microsurgical repair. Histopathology indicated that the vast majority of lesions in veins were removed at resection. Surgeon A achieved 75% patent arteries and Surgeon B achieved 100% arterial patency (resecting 3.7 mm more on average than Surgeon A). Histopathology revealed numerous luminal circumferential lesions remained in the avulsed artery wall following resection. These lesions were sites of smooth muscle cell proliferation and neointima formation. Although similar arterial damage occurs in human avulsion, considerably lower patency rates are achieved for human arterial avulsion repair than were reported in this experimental study. Factors in addition to vessel wall damage must therefore be involved in thrombosis and occlusion of repaired avulsed arteries. Such factors might be lengthy ischaemia time and severe spasm.     

The High Mortality of Gastrointestinal Bleeding in HIV-Seropositive Patients: A Multivariate Analysis of Risk Factors and Warning Signs of Mortality in 50 Consecutive Patients

The patterns of which human immunodeficiency virus (HIV)-seropositive patients underwent endoscopy for gastrointestinal bleeding at a university hospital were analyzed in 50 consecutive patients admitted from July 1984 through December 1989, and criteria were developed as to which patients are most likely to benefit from endoscopy. Analyzed patient data included the medical records, follow-up until July 1990 obtained by telephone questionnaire in 46 patients, and autopsy findings in the 11 patients undergoing autopsy. Thirty-seven percent of the patients did not undergo endoscopic or radiographic examinations indicated to determine the cause of bleeding. The adequacy of the evaluation was not related to race, intravenous drug abuse, homosexuality, hemophilia, the diagnosis of known AIDS, or being a public patient. In 21 of the 28 cases in which the cause of bleeding was determined, the diagnosed lesions had a specific, effective therapy. The mortality from gastrointestinal bleeding was 39.0%, compared with 8.3% in 48 controls without known HIV infection (p less than 0.001 by Fisher's exact test, odds ratio = 7.0, odds ratio confidence interval = 5.0-9.7). Statistically significant independent predictors of mortality included leukocytosis, concurrent major diseases, intravenous drug abuse, transfusion of 5 or more units of packed erythrocytes, and the presence of a bloody nasogastric aspirate or hematemesis (Wilk's lambda statistic = 0.369, p less than 0.0001). In particular, 10 of 11 patients (89%) with two or more concurrent major diseases died, whereas only three of 24 patients (13%) with no concurrent diseases died during the hospitalization. We conclude a large percentage of HIV-seropositive patients did not undergo a diagnostic evaluation for gastrointestinal bleeding at a university hospital, and there was no discernible rational pattern as to which patients underwent endoscopy. Endoscopy is an important and indicated procedure in HIV-seropositive patients with no or one concomitant major illness. HIV-seropositive patients with gastrointestinal bleeding and two or more concomitant major illnesses have an exceedingly poor prognosis, and are less likely to benefit from invasive diagnostic tests and aggressive therapy.     

Changes in myocardial echo amplitude during reversible ischaemia in humans.

OBJECTIVE--This study investigated the changes in regional myocardial ultrasonic backscatter, measured as myocardial echo amplitude, that occur during reversible myocardial ischaemia in humans. DESIGN--Left anterior descending coronary angioplasty was used to produce reversible myocardial ischaemia in human subjects. Regional myocardial echo amplitude was studied in the interventricular septum and left ventricular posterior free wall before, during, and after coronary occlusion with the angioplasty balloon. Wall motion analysis of the left ventricle was performed from simultaneous cross sectional echocardiographic imaging. Patients were studied prospectively. PATIENTS--Six patients (mean age 56 (SD 11), range 46 to 69 years) with single vessel, left anterior descending coronary artery stenoses, were investigated during elective coronary angioplasty. A total of 11 balloon inflations were studied. SETTING--All patient studies were performed at Harefield Hospital. Echo amplitude analysis was performed at the Royal Brompton Hospital. INTERVENTIONS--Angioplasty was performed by the usual procedure at Harefield Hospital for elective coronary angioplasty. All routine medication including beta blockers and calcium antagonists were continued. Inflation pressures were up to 12 atm (1212 kPa) and mean inflation time ranged from 30 to 120 (86 (31)) s. In four studies the first inflation was examined, in three the second, in two the third, and in one each the fourth and fifth inflations. Echo amplitude and cross sectional echo-cardiographic studies were recorded with a 3.5 MHz Advanced Technology Laboratories (ATL) (720A/8736 series) mechanical sector scanner and an ATL Mark III (860-1 series) echocardiograph system with 45 dB logarithmic grey scale compression. MAIN OUTCOME MEASURES--Regional echo amplitude was examined in four regions of the left ventricle--namely, the basal and mid-septum, and basal and mid-posterior wall. Consecutive end diastolic and end systolic frames were analysed and cyclic variation was determined as the difference between the level of echo amplitude at end diastole and at end systole. Measurements were made before balloon inflation, at peak inflation, and after balloon deflation. Regional wall motion and systolic wall thickening were analysed qualitatively. RESULTS--Before balloon inflation, cyclic variation in echo amplitude was noted in all regions (basal septum, 2.4 (SD 1.1) dB; mid-septum, 2.5 (1.1) dB; basal posterior wall, 3.3 (2.1) dB; mid-posterior wall, 3.9 (1.6) dB). During balloon inflation there was a significant fall in cyclic variation to 0.4 (0.9) dB (p < 0.0002) in the mid-septum. This was predominantly owing to an increase in end systolic echo amplitude from 5.4 (2.0) dB to 9.3 (1.9) dB (p < or = 0.01). This was associated with the development of severe hypokinesis or akinesis in the mid-septum. No significant changes in echo amplitude occurred in the three other regions examined. Changes were completely reversed after balloon deflation. CONCLUSIONS--These results suggest a causal relation between occlusion of the supplying coronary artery and blunting of myocardial echo amplitude cyclic variation. It is suggested that balloon occlusion produced myocardial ischaemia. The resultant impairment of myocardial contraction then caused a blunting of cyclic variation in echo amplitude. The results of this study provide further data about the ability of quantitative studies of ultrasonic backscatter to identify alterations in the myocardium during injury.     

Malaria parasite invasion: interactions with the red cell membrane

The capacity to invade red cells is central to the biology of malaria parasites; both asexual multiplication and reinfection of the definitive mosquito host depend upon intraerythrocytic stages. The invasion process is complex. The briefly free merozoite specifically recognizes and adheres to ligands on the red cell surface, then alters the red cell membrane to produce an invagination into which it moves, and so becomes enclosed in a membrane-bound parasitophorous vacuole. Here we assess new evidence that bears on our understanding of this process. This has come from sources including biochemical and ultrastructural studies of the specialized surface and organelles of merozoites, from in vitro invasion studies using naturally refractory or artificially modified red cells, and from structural, chemical, and immunological analyses of the newly parasitized cell.