The induction of operational tolerance is not prevented by simultaneous administration of cyclosporin A1

In this study, the effect of combining anti-CD4 monoclonal antibody (mAb) and cyclosporin (CyA) therapy at the time of transplantation was examined. A mouse cardiac allograft model was used. Anti-CD4 mAb administered perioperatively induces long-term survival. The addition of a short course of CyA given subcutaneously in a regimen of either a high-dose treatment or a standard dose treatment to the anti-CD4 mAb treatment protocol did not have a detrimental effect on graft survival. Despite having no significant effect on graft survival, the addition of CyA to the treatment protocol did result in a significant decrease in the level of IL-2 present in the hearts 7 days after transplantation. The decrease in IL-2 production was directly related to the presence of CyA in vivo. When CyA treatment was continued throughout the period during which unresponsiveness to the graft is induced by anti-CD4 mAb therapy, 50 % of the grafted hearts were rejected once the CyA was discontinued. In conclusion, the combined use of anti-CD4 mAb therapy and CyA did not have a negative effect on graft survival in this model when the two agents were used concurrently at the time of transplantation. Received: 2 October 1996 Received after revision: 31 January 1997 Accepted: 5 February 1997     

Repeat hepatic resections for colorectal metastases

We identified 106 patients who had undergone complete resection of isolated colorectal hepatic metastases. Nine of these patients subsequently underwent repeat liver resections for isolated hepatic recurrences. The median follow-up for these patients was 21 months. One postoperative death was related to the second hepatectomy. At the time of last follow-up, five patients were alive and free of recurrent disease at 9, 19, 31, 50, and 67 months after their second hepatic resection. The remaining three patients were alive, but disease had recurred 11 months after resection in the first patient, 12 months after resection in the second, and 18 months after resection in the third. Among these three patients, two had solitary pulmonary nodules, which were resected, and one had unresectable liver disease. Our experience and a review of the literature suggest that repeat hepatic resection for isolated colorectal metastases can result in long-term survival in selected patients.     

Abolition of flow-dependent EDRF release before that evoked by agonists in hypercholesterolaemic rabbits.

1. We have used a pulsatile cascade bioassay system to investigate the effects of dietary-induced hypercholesterolaemia on EDRF release evoked by acetylcholine and by the oscillatory and time-averaged components of flow, in isolated segments of rabbit abdominal aorta. 2. Flow pulsatility (frequency range 0.1-10 Hz) was studied with constant flow (9 ml min-1) at a pulse pressure amplitude of 2 mmHg. Frequency-related EDRF release, maximal at 6 Hz, was slightly attenuated after 4 weeks and abolished after 8 weeks of cholesterol feeding. 3. Time-averaged shear stress was manipulated with dextran (1-4% w/v, 80000 mol. wt.), to increase perfusate viscosity. EDRF release induced by increased perfusate viscosity was unaffected after 4 weeks but abolished after 8 weeks of cholesterol feeding. 4. Endothelium-dependent relaxations to acetylcholine (0.1-10 microM) were not influenced after 4 weeks and only partially attenuated (by 60% of the maximal response, EC50 unchanged at 6.45 +/- 0.04 vs. 6.4 +/- 0.1 microM) after 8 weeks of cholesterol feeding. 5. Blood cholesterol levels were significantly (P < 0.001) increased after 4 weeks (26 +/- 3.6 vs 2.6 +/- 0.6 mmol l-1) and 8 weeks (56.2 +/- 3.8 vs 1.3 +/- 0.1 mmol l-1) of cholesterol feeding but after 8 weeks plasma L-arginine levels were not significantly different from the age-matched controls (0.2 +/- 0.05 vs. 0.19 +/- 0.04 mmol l-1). 6. We conclude that hypercholesterolaemia impairs flow-related (pulsatile- and time-averaged shear-induced) EDRF release earlier than acetylcholine-induced relaxation in rabbit aorta.(ABSTRACT TRUNCATED AT 250 WORDS)     

The Effect of High-Dose Ascorbate Supplementation on Plasma Lipoprotein(a) Levels in Patients With Premature Coronary Heart Disease

Study Objective . To determine the efficacy of high-dose ascorbate supplementation in lowering lipoprotein(a) [Lp(a)] levels in patients with premature coronary heart disease (CHD). Design . Randomized, double-blind, placebo-controlled trial. Setting . Outpatient clinic. Patients . Forty-four patients with documented premature CHD. defined as confirmed myocardial infarction and/or angiographically determined stenosis of 50% or greater in at least one major coronary artery before age 60 years. Interventions . Patients were block randomized on the basis of age, gender, and screening Lp(a) concentrations to receive ascorbate 4.5 g/day or placebo for 12 weeks. Measurements and Main Results . High-dose ascorbate was well tolerated and produced a marked elevation in mean plasma ascorbate levels (+1.2 mg/dl; p<0.001). Multiple linear regression analysis revealed no significant effect of supplementation on postintervention Lp(a) levels (p=0.39) in a model that included treatment group assignment, and baseline Lp(a) levels. Conclusions . Our findings do not support a clinically important lowering effect of high-dose ascorbate on plasma Lp(a) in patients with premature CHD.     

Mixed h2 and h∞ optimal robust control design

This paper introduces a design methodology for a dynamic compensator that simultaneously minimizes the upper bound of a quadratic performance index and the H_∞-norm of a disturbance transfer function matrix of a multiple-input/multiple-output system whose model contains parameter uncertainty in the state and input matrices. The real parameter uncertainty is modelled as additional measurement outputs and as additional weights on the existing noise inputs and measurement outputs of the system. The compensator equations are derived by taking the dual of a system with parameter variation in the state and output matrices, for which the compensator equations have previously been derived, and then taking the dual of the compensator equations. An algorithm for applying this theory is given and an example is shown.     

Are Continuity Clinic Patients Less Satisfied When the Resident Is Postcall?

Due to recent public debate and newly imposed resident work hour restrictions, we decided to investigate the relationship of resident call status to their ambulatory patients' satisfaction. Resident continuity clinic patients were asked to rate their level of satisfaction on a 10-point Likert-type scale. Using multiple regression approaches, these data were then assessed as a function of resident call status. We found that in 646 patient encounters, patient satisfaction scores were significantly less when the resident was postcall, 8.99 ± 1.8, than when not postcall, 9.31 ± 1.3. We herein discuss etiologies and implications of these findings for both patient care and medical education.