Clinical benefits and tolerability of increased fill volumes in Japanese peritoneal dialysis patients.

BACKGROUND: Increasing fill volume is an effective means of improving clearances in patients on peritoneal dialysis (PD). Since Japanese PD patients are physically smaller than their Western counterparts, there is some concern that PD patients in Japan may be unable to tolerate larger fill volumes. OBJECTIVE: To determine patient tolerance and changes in solute clearance and net ultrafiltration resulting from increased fill volumes in Japanese patients on PD. DESIGN: Prospective double-blind study, randomizing patients to three different fill volumes (2.5% dextrose solution: 1.5 L, 2.0 L, or 2.5 L) administered in random order on three different occasions separated by 1 week. RESULTS: Twenty-one patients with a mean age of 55.4 +/- 2.1 years and a mean body surface area of 1.66 +/- 0.03 m2 were studied. On a scale of 0 to 10, patients' mean discomfort scores were 2.14 +/- 0.59, 3.48 +/- 0.54, and 3.81 +/- 0.63 (p = 0.047) at the end of the 1.5-L, 2.0-L, and 2.5-L dwells, respectively. There were no reports of cramps or shortness of breath with any fill volume. Patients were able to correctly guess the actual fill volume for only 34 of the 63 total exchanges (54.0%). Increasing fill volume resulted in an incremental improvement in peritoneal creatinine clearance, from 3.74 +/- 0.16 to 4.49 +/- 0.21 (p < 0.001, 2.0 L vs 1.5 L) to 5.12 +/- 0.20 mL/minute (p< 0.001, 2.5 L vs 2.0 L) for 1.5-L, 2.0-L, and 2.5-L dwells, respectively. Peritoneal urea clearance also increased significantly, from 5.65 +/- 0.13 to 7.04 +/- 0.17 (p < 0.001, 2.0 L vs 1.5 L) and 8.16 +/- 0.29 mL/minute (p < 0.001, 2.5 L vs 2.0 L), with incremental increases in fill volume. Similarly, net ultrafiltration in a 4-hour dwell increased significantly with fill volume, from 255.24 +/- 24 mL with 1.5 L, to 356 +/- 24 (p < 0.004, 2.0 L vs 1.5 L) and 392 +/- 29 mL (p < 0.086, 2.5 L vs 2.0 L) in patients receiving 2.0 L and 2.5 L, respectively. CONCLUSION: Increasing the fill volume results in improvement in solute clearance and net ultrafiltration in Japanese PD patients, with minimal increase in patient discomfort. A large percentage of patients were unable to identify the actual fill volume.

Replacement of amino acid and protein losses with 1.1% amino acid peritoneal dialysis solution.

OBJECTIVE: Losses of nutrients into dialysate may contribute to malnutrition. Peritoneal dialysis (PD) patients are reported to lose 3-4 g/day of amino acids (AAs) and 4-15 g/day of proteins. The extent to which one exchange with a 1.1% AA dialysis solution (Nutrineal, Baxter, Deerfield, IL, U.S.A.) offsets these losses was investigated in a 3-day inpatient study in 20 PD patients. DESIGN: Simple, open-label, cross-over study on consecutive days in a clinical research unit. On day 1 all patients were given a peritoneal equilibration test (PET). On day 2 they received 1.5% dextrose Dianeal (Baxter) as the first exchange of the day and their usual regimen thereafter. On day 3, the first exchange of the day was the 1.1% AA solution in place of 1.5% Dianeal and the usual PD regimen thereafter. On days 2 and 3 all dialysate effluent was collected and analyzed for AAs and proteins. Patients were maintained on a constant diet. RESULTS: Losses of AAs and total proteins on day 2 were 3.4 +/- 0.9 g and 5.8 +/- 2.4 g, respectively, totaling 9.2 +/- 2.7 g. The net uptake of AAs on day 3 was 17.6 +/- 2.6 g (80 +/- 12% of the 22 g infused). Mean gains of AAs on day 3 exceeded losses of proteins and AAs on day 2, p < 0.001. Losses of total proteins, but not losses of AAs, and the net absorption of AAs from the dialysis solution were correlated directly with peritoneal membrane transport characteristics, obtained from the PET. CONCLUSION: Daily losses of AAs and proteins into dialysate are more than offset by gains of AAs absorbed from one exchange with 1.1% AA-based dialysis solution. Net gains of AAs exceeded losses of proteins and AAs in all patients studied. The difference was relatively constant across a wide range of membrane transport types. Net AA gains were approximately two times the total AA and protein losses.

Efficacy and safety of intracavernosal alprostadil in men with erectile dysfunction. The Alprostadil Study Group.

BACKGROUND: Erectile dysfunction is a common medical problem affecting many men. Although several intracavernosal therapies are available, their efficacy and safety have not been studied systematically. METHODS: We investigated the efficacy and safety of alprostadil formulated for intracavernosal treatment in three separate multi-institutional, prospective studies in men with erectile dysfunction of vasculogenic, neurogenic, psychogenic, and mixed causes. Clinical and laboratory evaluations of erection and the feasibility of satisfactoriness of sexual activity as assessed both by the men and by their partners were the primary measures of efficacy. RESULTS: In a dose-response study of 296 men, all doses of alprostadil were superior to placebo and there was a significant dose-response relation (P < / = 0.001), resulting in higher response rates with increasing doses of alprostadil (from 2.5 to 20 microg). In a dose-finding study of 201 men, the minimal effective dose was < / = 2 microg in 23, 20, 38 and 23 percent of men with erectile dysfunction of neurogenic, vasculogenic, psychogenic, or mixed causes, respectively. In a six-month self-injection study in 683 men, the participants reported being able to have sexual activity after 94 percent of the injections. The men and their partners rated the sexual activity as satisfactory after 87 and 86 percent of the injections, respectively. Penile pain, usually mild, occurred in 50 percent of the men at some time but after only 11 percent of the injections. Prolonged erections occurred in 5 percent of the men, priapism in 1 percent, penile fibrotic complications in 2 percent, and hematoma or ecchymosis in 8 percent. CONCLUSIONS: In men with erectile dysfunction, intracavernosal injection of alprostadil is an effective therapy with tolerable side effects.

A study in patients with erectile dysfunction comparing different formulations of prostaglandin E1. Alprostadil Study Group.

PURPOSE: Prostaglandin E1 sterile powder and sterile solution are 2 new formulations of exogenous prostaglandin E1 that are more convenient for auto-injection therapy for erectile dysfunction than the presently used pediatric sterile solution. Therefore, the pharmacodynamic profiles of intracavernous prostaglandin E1 sterile powder and nonalcohol sterile solution were compared with the pediatric sterile solution in men with erectile dysfunction who were known to be stable responders to intracavernous prostaglandin E1. MATERIALS AND METHODS: Based on the dose used at home, patients were randomized to 1 of 5 dose groups: 0 microgram. (placebo), 2.5 micrograms., 5 micrograms., 10 micrograms. or 20 micrograms. Each patient received a single injection of the same dose of each of the 3 formulations. The primary pharmacodynamic end points were clinical evaluation of erectile response, RigiScan real-time evaluation of erectile response and patient evaluation of erectile response. RESULTS: No significant differences were identified among the formulations for any of these end points, either by comparison among all active doses or by comparison at each prostaglandin E1 dose level. There was also little or no intra-patient variation in dose response and the inter-dose variation in response between patients was not significant. Pharmacodynamic end points were well intercorrelated, although assessment of erectile response by the patients tended to be more positive than that by RigiScan or clinical evaluation. There were no major side effects. Penile pain on injection and/or during erection occurred in 9 to 17% of the patients according to the formulations. However, penile pain was also reported by 11% of the placebo-treated patients. CONCLUSIONS;: The 3 formulations of prostaglandin E1 showed equivalence and were safe for the treatment of erectile dysfunction with respect to side effects.

Evaluation of real-time RigiScan monitoring in pharmacological erection.

PURPOSE: The clinical assessment of pharmacologically induced erectile response was compared to the real-time RigiScan* monitoring response. MATERIALS AND METHODS: Erection was induced by 521 intracavernous injections of a new alprostadil formulation. The clinical end point was "full rigidity" and the RigiScan criterion was radial rigidity of 70% or more for 10 consecutive minutes or longer. RESULTS: For 752 prostaglandin E1 injections the sensitivity and specificity of the RigiScan device compared to clinical evaluation were 53.8% (133 of 247 cases) and 92.9% (469 of 505), respectively. For rigidity of 60% or greater the sensitivity increased to 70.8% (175 of 247 cases) and specificity decreased to 85.0% (429 of 505). CONCLUSIONS: The RigiScan device is useful to document objectively a pharmacologically induced erection yet it appears to be more conservative than clinical evaluation.

Efficacy and safety of reformulated, micronized glyburide tablets in patients with non-insulin-dependent diabetes mellitus: a multicenter, double-blind, randomized trial.

The subjects were 206 patients (123 men, 83 women) with non-insulin-dependent diabetes mellitus, aged 33 to 80 years. For at least 4 weeks prior to the study each subject had been taking 5-mg tablets of original, nonmicronized glyburide (Micronase tablets) in doses of 5, 10, 15, or 20 mg daily. In a double-blind 12-week study, the subjects were randomly assigned to continue receiving 5-mg tablets of original glyburide or to substitute 3-mg tablets of reformulated, micronized glyburide (Glynase PresTab tablets) for the original tablets. Glyburide tablets had been reformulated to improve their bioavailability. Baseline mean fasting serum glucose levels in the groups taking reformulated and original glyburide were 169.3 and 168.3 mg/dl, respectively; at study end point, their respective serum glucose levels were 186.0 and 177.0 mg/dl. The differences between groups were not significant; in both groups, however, end point glucose levels were significantly higher than baseline levels. Baseline hemoglobin A1C levels in the groups taking reformulated and original glyburide were both 7.6%; at study end point, hemoglobin A1C levels had improved slightly in each group to 7.4% and 7.5%, respectively. The differences between and within groups at end point were not significant. No between-group differences at baseline or at end point were found in mean levels of postprandial serum glucose, fasting C-peptide, or postprandial C-peptide. Medical events experienced by the subjects in the two groups were similar in nature and number. Changes in other laboratory test results, vital signs, and weight were not clinically meaningful.(ABSTRACT TRUNCATED AT 250 WORDS)