Maintenance immunosuppression: new agents and persistent dilemmas.

Since the approval of cyclosporine in 1983, only 3 drugs, mycophenolate mofetil, tacrolimus, and sirolimus, have been approved for maintenance immunosuppression in renal transplant recipients. All 3 agents decrease the incidence of early acute allograft rejection. An increase in intermediate and long-term graft survival has not been shown. However, survival data from these clinical trials should be interpreted with caution because the studies were not designed for this purpose. All 3 drugs have significant, albeit different, safety profiles. It remains to be seen whether, the lower incidence of hypertension and hyperlipidemia seen in tacrolimus-treated patients will reduce the incidence and severity of the cardiovascular disease experienced by renal transplant recipients. Sirolimus causes severe hyperlipidemia, and the long-term consequences both on the pathogenesis of cardiovascular disease and on lipid-associated renal injury have yet to be determined. Tacrolimus and mycophenolate mofetil appear to increase graft survival in pancreas-kidney recipients but their efficacy in another high-risk group, African-American recipients, has not yet been clearly shown. However, the trend toward improved graft survival in African-American recipients treated with tacrolimus is encouraging. Steroid-withdrawal remains a goal in the posttransplant period. The available data from steroid-withdrawal and steroid-avoidance clinical trials are mixed. Steroid withdrawal can be achieved in about 50% of patients on a cyclosporine-based immunosuppression regimen. Steroid-withdrawal under coverage of tacrolimus, mycophenolate mofetil or Neoral (Novartis Pharmaceuticals, East Hanover, NJ) may be more successful than that achieved in patients receiving Sandimmune (Novartis Pharmaceuticals). Further studies are needed in this area.

Corrected Q-T interval prolongation as diagnostic tool for assessment of cardiac autonomic neuropathy in diabetes mellitus.

A simple method for evaluating alterations in cardiac sympathetic innervation may be measurement of the Q-T interval. Seventy-three diabetic patients (46 insulin dependent and 27 non-insulin dependent) were separated into four groups based on the presence and degree of cardiac autonomic neuropathy (CAN) with noninvasive cardiovascular reflexes and blood pressure responses. None of the patients had evidence of ischemic heart disease, kidney disease, or the idiopathic long Q-T-interval syndrome. The corrected Q-T interval (Q-Tc) was determined at rest with Bazett's formula. As a group, diabetic patients with greater than or equal to 2 abnormalities of cardiac autonomic function had a longer Q-Tc interval than those with no evidence of CAN. Diabetic patients with greater than or equal to 1 abnormality had a prolonged Q-Tc interval compared with a control group of 96 healthy nondiabetic subjects (mean +/- SD 397 +/- 18). The frequency of prolonged (greater than 433 ms, normal mean + 2SD) resting Q-Tc intervals increased with the increasing number of abnormalities (0, 1, 2, greater than or equal to 3): 11, 25, 41, and 75%, respectively. Twenty-three of 25 (92%) patients with a Q-Tc greater than 433 ms had evidence of CAN. However, 57% (31 of 54) of the patients with CAN had a normal Q-Tc interval. These data provide further evidence of a relationship between the presence and severity of CAN and degree of Q-Tc interval prolongation.(ABSTRACT TRUNCATED AT 250 WORDS)

Demonstration by iodine-131-hippurate renography of a marked sensitivity of some transplanted kidneys to volume contraction.

Incidental observations made in a canine renal transplant model in which both native and transplanted kidneys were present revealed that abnormal I-131-iodohippurate renograms were derived from some of the transplanted kidneys in the presence of mild dehydration. In these cases, the renogram normalized with fluid administration. In contrast, the renograms derived from the native kidneys were unaffected by the mild dehydration of the animals. These findings demonstrate a greater sensitivity to dehydration of some transplanted kidneys when compared to normal kidneys.

Syphilis--an appraisal of the Groote Schuur Hospital antenatal screening programme.

Syphilis is a major public health problem in pregnant women. Since congenital syphilis is preventable, an adequate screening programme is an essential facet of antenatal care. At Groote Schuur Hospital, Cape Town, the Venereal Disease Research Laboratory and Treponema, pallidum haemagglutination tests are employed for antenatal screening. A survey of the current literature on serological testing for syphilis does not reveal clear guidelines for an optimal antenatal screening programme. The high prevalence of syphilis in pregnant women is confirmed by this study, which shows the current programme to be very effective in excluding women without disease.