Autonomic and renal effects of intravenous diazoxide. A study of the mechanisms of its hypotensive action in man

Summary Intravenous diazoxide produced an immediate marked hypotension in both mild and severe hypertensive patients. Depression of vasomotor reflexes, tested by the Valsalva overshoot, and of pressor responsiveness to noradrenaline was found only in the group of mild hypertensives. Decreased pressor reactivity to noradrenaline was not due to a nonspecific vascular effect of diazoxide, because pressor responsiveness to angiotensin was simultaneously increased. Renal tubular reabsorption of sodium and water was increased shortly after injection of diazoxide, and there was also a significant retention of potassium. Correlation studies suggest that interference with vasomotor reflexes, and with vascular responsiveness to the sympathetic transmitter, can account only in part for the hypotensive action of diazoxide. The possible rôles of water and electrolyte redistribution remain to be elucidated.     

Results of lis2t, a multicenter, randomized study comparing cyclosporine microemulsion with C2 monitoring and tacrolimus with C0 monitoring in de novo liver transplantation

This is the first multicenter, randomized, open-label study to compare the efficacy and safety of cyclosporine A microemulsion (CsA-ME) (Neoral, Novartis, Basel, Switzerland ) with C2 monitoring versus tacrolimus in de novo liver transplant recipients. Patients were stratified according to hepatitis C virus status and randomized to receive CsA-ME (n= 250) or tacrolimus (n= 245) with steroids, with or without azathioprine. The primary endpoint was the incidence of biopsy-proven acute rejection (BPAR) at 3 months. Secondary endpoints included death or graft loss and safety evaluations at 6 months. The incidence of BPAR at 3 months was 26% in the CsA-ME group and 24% in the tacrolimus group (not significant). At 6 months, 89% of patients receiving CsA-ME and 88% of patients receiving tacrolimus were alive with a functioning graft. Among the hepatitis C virus-positive patients, there was no difference in BPAR, but death or graft loss was more frequent in those receiving tacrolimus (15% vs. 6%, P <0.05). Diabetes mellitus (14% vs. 7%, P <0.02) and diarrhea (29% vs. 14%, P <0.001) were significantly more often reported in patients receiving tacrolimus. The incidence of hypertension was similar in both groups. At 6 months, the median total cholesterol was 4.7 mmol/L (2.9-7.4 mmol/L) in the CsA-ME arm versus 4.3 mmol/L (2.5-6.4 mmol/L) in the tacrolimus arm; the median serum creatinine was 106 micromol/L (52-238 micromol/L) in the CsA-ME arm versus 103 micromol/L (44-477 micromol/L) in the tacrolimus arm. Efficacy is equivalent with CsA-ME using C2 monitoring or tacrolimus in liver transplant recipients. The incidence of adverse events is comparable except for a significantly higher incidence of diabetes mellitus and diarrhea in the tacrolimus group. Both agents are effective primary immunosuppressants in liver transplant recipients.     

Partial necrosis on hepatocellular carcinoma nodules facilitates tumor recurrence after liver transplantation

BACKGROUND: The presence of partial necrosis in hepatocellular carcinoma (HCC) nodules is a common histologic finding after liver transplantation, but its correlation with tumor recurrence has never been investigated. METHODS: we retrospectively reviewed the outcome of 54 patients with a single histologically proven HCC after liver transplantation. All cases had a survival of more than 6 months, and patients treated preoperatively had a transarterial chemoembolization (TACE) procedure. Since 1996, our center has applied the Milan criteria. Correlations between tumor recurrences and clinicopathologic variables, including the presence of partial necrosis, were performed. Etiologic factors for HCC partial necrosis were also investigated. RESULTS: Sixteen of 54 (29.6%) HCC nodules presented partial necrosis, and 4 (25%) of them developed HCC recurrence compared with 1 of 38 (2.6%) cases without this histologic finding (P<0.05). Partial necrosis was related to TACE procedure (P<0.05), patient age less than 50 years (P<0.05), and tumor diameter greater than 2 cm (P<0.05). Multivariate analysis showed only TACE as an independent variable. The other variables related to the five (9.3%) tumor recurrences were HCC diameter greater than 2 cm (P<0.05), year of liver transplantation before 1996 (P<0.05), and the presence of satellite nodules (P<0.05). The Cox regression analysis showed the presence of partial necrosis as an independent variable related to tumor recurrence. The analysis of the recurrence-free survival confirmed the results of the recurrence rate. CONCLUSION: Partial necrosis was a risk factor for tumor recurrence after liver transplantation. Patients and procedures should be selected while also bearing in mind the side-effect of incomplete necrosis of the nodules.     

Extremes of body mass index do not affect first-trimester pregnancy outcome in patients with infertility

OBJECTIVE: The study was undertaken to ascertain whether body mass index (BMI) affects first-trimester pregnancy outcome in patients with infertility. STUDY DESIGN: Records of 494 patients with a singleton gestation after treatment for infertility at a single academic center were retrospectively reviewed. Patients were classified with regard to BMI and treatment protocol. Outcomes were defined as ongoing pregnancy, spontaneous abortion, or ectopic pregnancy. RESULTS: The average rate of spontaneous abortion was 21.5% and of ongoing pregnancy 75.1%. This did not differ significantly in any of the BMI groups. When patients were further subdivided according to diagnosis or fertility treatment, the spontaneous abortion rate remained the same. CONCLUSION: The likelihood of a spontaneous abortion, ongoing pregnancy, or ectopic pregnancy in singleton gestations in the first trimester, after treatment for infertility, was not affected by BMI.     

Nonaltruistic kidney donations in contemporary Jewish law and ethics

BACKGROUND: In 2000, the Consensus Statement on the Live Organ Donor reported that "direct financial compensation for an organ from a living donor remains controversial and illegal in the United States" and took note of the position of the Transplantation Society that "Organs and tissue should be given without commercial consideration or commercial profit." Christian authorities insist that organ donors must not accrue economic advantage, and "selling" organs deprives the donation of its ethical quality. METHODS: The writings of major contemporary authorities of Jewish law and ethics whose halakhic positions on bioethical issues are regularly considered by Orthodox, Conservative, and Reform ethicists were reviewed. Their positions on this issue were contrasted with those of various contemporary secular and religious authorities. RESULTS: These Jewish authorities reject the notion that generosity and charity, rather than monetary gain and greed, must serve as the exclusive basis for donation of functioning organs. CONCLUSION: Although nonaltruistic sale of kidneys may be theoretically ethical, ultimately its ethical status in Jewish ethics and law is inextricably connected to solving a series of pragmatic programs, such as creating a system that ensures that potential vendors and donors are properly informed and not exploited. Lacking such arrangements, ethical nonaltruistic kidney donations remain but a theoretical possibility.     

Respiratory function after repair of congenital diaphragmatic hernia

Respiratory function studies were carried out in 22 infants who had successful repair of diaphragmatic herniae of the Bochdalek type. Thoracic gas volume was initially reduced in only 3 of these, but subsequent studies showed that improvement occurred. There were no consistent abnormalities in either dynamic compliance or mean pulmonary conductance. This is evidence that there is rapid adaptation which compensates for any alteration in the parenchymatous tissue in the lungs or abnormalities in the bronchial tree in infants soon after the repair of congenital diaphragmetic herniae. Further studies are necessary to determine the changes in these lungs with growth.