Remission of nephrotic range proteinuria in type I diabetes. Collaborative Study Group.

The present study assessed the extent to which remission of nephrotic-range proteinuria occurred in patients with Type I diabetes enrolled in the Captopril Study, a placebo controlled multicenter clinical trial of captopril therapy in diabetic nephropathy. Of the 409 patients recruited into the Captopril Study, 108 had nephrotic-range proteinuria (> 3.5 g/24 hr) at entry in the Study (baseline). This group was the subject of the present study. Remission of nephrotic-range proteinuria was defined as follows: (1) Onset of the remission was taken as the date when proteinuria was first noted to be < or = 1.0 g/24 hr. (2) The reduction in proteinuria had to be sustained for a minimum of six months and until the end of the Captopril Study. (3) During the remission, the average of all 24 hour proteinuria measurements could not exceed 1.5 g. (4) Decline in renal function could not explain the reduced proteinuria. That is, the patient's serum creatinine during the entire period of observation in the Captopril Study had to remain at less than a doubling of the baseline serum creatinine. Remission of nephrotic-range proteinuria occurred in 7 of 42 patients assigned to captopril (16.7%, mean follow-up 3.4 +/- 0.8 years) and in 1 of 66 patients assigned to placebo (1.5%, mean follow-up 2.3 +/- 1.1 years; P = 0.005, comparing remission rate in captopril vs. placebo-treated patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for the potential influence of cyclic nucleotides on maintenance of or reactivation from latency of herpes simplex virus in trigeminal ganglionic neurons.

Herpes simplex virus infections are epidemic throughout developed countries, and recurrent herpes simplex keratitis is the most common cause of corneal blindness in these countries, NIH (1973). No available antiviral agent is capable of eradicating the state of viral ganglionic latency, and hence no effective treatment currently exists for prevention of viral re-activation from latency, with resultant recurrent infectious viral clinical manifestations. Putative triggers of re-activation include stress, sunburn, menses, trauma, and fever. These 'triggers' seem to share at least one common characteristic: the potential ability to influence intracellular cyclic nucleotide levels through the action of such first order messengers as catacolamines (stress, trauma) and/or arachadonic acid metabolites (sunburn, fever, trauma, and menses). We exploited an in vitro model of HSV ganglionic latency, and developed a model of in vitro organ culture ganglionic viral reactivation from latency. We then examined the effect of a variety of agents on this model. We found that agents which have been shown to elevate cyclic AMP levels consistently produce increased viral shedding (compared to control, spontaneous reactivation rate) in our model of viral reactivation from latency. In contrast, agents which have been shown to depress c-AMP levels and/or to elevate c-GMP levels inhibit viral reactivation from latency in this in vitro model. We conclude that intracellular cyclic nucleotide levels may influence events which control herpes simplex genome transcription.

Respiratory gas exchange by high-efficiency hemodialyzers.

The effects of respiratory gas mass-transfer by high-efficiency hemodialyzers with regard to respiratory status and acid-base balance were studied in three groups of patients. Patients dialyzed with acetate dialysate and a single pass delivery system (group I) and those dialyzed with the same dialysate and a recirculating single pass system (group II) had significant intradialytic decreases in PCO2 (p is less than 0.05), while patients hemodialyzed aginst a carbon dioxide/bicarbonate dialysate (group III) had no significant alterations in arterial PCO2. The massfransfer rate of carbon dioxide was 0.3 mM/min in group I and 0.2 mM/min in group II. The hypocapnia caused by dialyzer mass-transfer of carbon dioxide was associated with a significant drop in minute ventilation volume and a decrease in PO2 which was significant in group I (p is less than 0.05). Although bicarbonate mass-transfer reduced serum bicarbonate levels, the loss of carbon dioxide to the dialysate resulted in an increased arterial pH during dialysis.