The Influence of Dirithromycin on the Pharmacokinetics of Cyclosporine in Healthy Subjects and in Renal Transplant Patients

The effect of a standard regimen of the investigational macrolide antibiotic, dirithromycin, on the single-dose kinetics of orally administered cyclosporine (CSA) was investigated in healthy young males and on the steady-state disposition kinetics of cyclosporine in a panel of renal transplant patients. Eight male volunteers participated after giving informed consent. CSA was administered in three single doses (15 mg kg(minus sign1) p.o. each) in each of three phases: (1) prior to a 14-day regimen of dirithromycin; (2) at the end of a 14-day regimen of dirithromycin (500 mg p.o. qAM); and (3) 2 weeks after the last dose of a 14-day regimen of dirithromycin. Pharmacokinetic parameters of CSA were estimated, and the differences among treatments were assessed by analysis of variation. No significant differences among treatment (phase) means were detected (p < 0.05). We conclude that a typical 14-day regimen of dirithromycin failed to alter the disposition kinetics of CSA when taken orally healthy young adult males. The effect of a standard regimen of dirithromycin on the steady-state disposition kinetics of orally administered CSA was investigated in a panel of 15 stable renal transplant patients. Pharmacokinetic parameters for CSA were evaluated prior to, during, and 2 weeks after discontinuing a 14-day (500 mg day(minus sign1)) oral regimen of dirithromycin. Dirithromycin elicited small but significant changes in the following parameters: C(av) was increased by 16% during dirithromycin treatment, and the changes in normalized C(av) were comparable. Likewise, C(SS,min) and normalized C(SS,min) were increased by 19% and 20%, respectively, during dirithromycin treatment. CSA oral clearance, CL/F(SS), decreased by 17% during dirithromycin treatment. C(SS,max) and normalized C(SS,max) were increased by 13% and 17%, respectively, during dirithromycin treatment but were not significantly different from those either before or after dirithromycin. The magnitude of the pharmacokinetic changes for CSA during dirithromycin treatment (<15% in normal subjects and 15--20% in renal transplant patients) when considered in the context of the therapeutic range of cyclosporine concentrations was relatively small, and not likely to warrant special attention to the dosing of CSA in such patients beyond routine whole-blood CSA and serum creatinine monitoring.     

The necessity of a second prostate biopsy cannot be predicted by PSA or PSA derivatives (density or free:total ratio) in men with prior negative prostatic biopsies

Serum prostate specific antigen, prostate specific antigen density and free:total prostate specific antigen are known to be useful for determining the risk of prostate cancer in patients undergoing prostate cancer screening. The patient with a positive biopsy presents no future prostate specific antigen dilemma. Those with negative biopsies often go on to numerous repeat biopsies. Our goal was to establish criteria that could be used to identify patients who will require repeat prostate biopsies (possibly false negative initial biopsy), while not exposing the low risk population (probable true negative initial biopsy) to additional invasive procedures. Between March 1991 and March 1998, 148 patients who had a biopsy for an elevated prostate specific antigen value (4.1-10.0) or an altered digital rectal examination, had no cancer found in the specimen. From these, 51 (34.4%) had repeated biopsies, while the others persisted on close follow-up. We examined their serum prostate specific antigen, prostate specific antigen density and free:total prostate specific antigen value, as well as their age and histology results of the initial and repeat biopsy, to determine if any predictor of the need for a repeat biopsy could be identified. Eight (15.7%) from 51 men who had repeat biopsy had prostate cancer detected. Forty three (84.3%) patients persisted with a negative biopsy, despite filling the criteria for re-biopsy. Multivariate analysis failed to identify any significant predictors of prostate cancer in the repeat biopsy group. Despite initial success, the prostate specific antigen derivatives and free:total prostate specific antigen have not safely limited the number of biopsies performed for an abnormal prostate specific antigen (4.1-10.0). Neither prostate specific antigen density nor free:total prostate specific antigen predicted the need for repeat biopsy in this specific group. The results of this ongoing study demonstrate that to date, prostate specific antigen and prostate specific antigen derivatives can not be utilized to determine which patients will be at high risk for requiring repeat prostate biopsy. All patients must be closely monitored for evidence of a change in status from benign to malignant disease, and new markers for this purpose are urgently needed.     

The Ileal Ureter Neobladder is Associated with a High Success and a Low Complication Rate

Purpose

Several different methods to construct a bladder substitute after cystectomy have been described. We evaluated our experience with the Studer ileal ureter neobladder during the last 5 years.

Materials and Methods

We reviewed retrospectively the results in 32 patients who underwent construction of a slightly modified ileal neobladder from that originally described. Mean followup was 25 months (range 6 to 68).

Results

Patients experienced few complications and only 1 required reoperation. Daytime and nighttime continence rates were 94 and 74 percent, respectively. One patient sustained a ureteral stricture resulting in hydronephrosis (1 of 64 renal units).

Conclusions

The results reveal the ileal neobladder to be an easily constructed pouch with a low complication rate, and a high success rate in regard to continence and the establishment of adequate capacity at low pressure. Within the study period upper tract preservation was excellent. However, a 10 to 15-year followup is indicated to confirm our initial results.     

Human Immunodeficiency Virus Infection: Complications and Outcome of Orthopaedic Surgery

Orthopaedic surgeons practicing in areas with a high prevalence of human immunodeficiency virus (HIV) infection may expect that up to 7% of their patients who undergo emergent procedures and 1% to 3% of those who undergo elective surgery will be HIV-positive. Although basic science studies have demonstrated impairment of defenses to routine orthopaedic pathogens as well as to opportunistic organisms, clinical studies have shown that this impairment has not resulted in an increased incidence of postoperative infections or failure of wound healing in the asymptomatic HIV-positive patient. Even for the symptomatic patient, current medical management appears adequate to reduce the risk of early postoperative infection. The HIV-positive patient with a pros-thetic implant may be at increased risk for late hematogenous implant infection as host defenses diminish. Regular medical attention, prophylactic antibiotic therapy before dental work and invasive procedures, and early evaluation and treatment of possible infections are especially important in this setting. Decisions regarding elective surgery should be made on a risk-benefit basis. Because the risk of surgical complications increases with progression of the dis-ease, guidelines for elective surgery should include an assessment of the HIV-positive patient's immune status, including the CD4 lymphocyte count, history of opportunistic infection, serum albumin level, the presence of skin anergy, and the state of nutrition and general health.     

Pediatric emergency information sheet using a microcomputer

Calculating the appropriate dosage of a drug and the right equipment size during an emergency situation can be a time-consuming, frustrating, and error-prone process, considering the shortage of time during a resuscitation. A microcomputer program was developed to aid in the care of pediatric patients in emergency or 'code' situations. This is accomplished by use of a printout of a patient-specific chart for most needed critical care drugs and equipment used during an emergency. This program is written in "C" language and is menu-driven.     

Thoughts about encounters between nondisabled and disabled peers: Situational constraints,states-of-mind,valenced thought categories

This study explores three issues: thoughts and feelings of individuals with and without physical disabilities concerning encounters in different situations, ways of grouping self-statements into valenced categories, and use of states-of-mind (SOM) ratios as an alternative to positive and negative thought frequencies. Data from 127 able-bodied and 46 physically disabled college students indicate that, in everyday social encounters, nondisabled individuals' thoughts and feelings were more negative, while those of disabled individuals were more negative when helping was involved and when encounters centered on the impairment. Thus, problematic encounters between people with and without disabilities may be due to the reactions of individuals with disabilities in situations which involve help, and to reactions of able-bodied persons in everyday contexts. The data also confirm the utility of SOM ratios as an alternative to valenced frequencies in cognitive assessment: SOM scores discriminated groups when situational demands were manipulated and scores were linearly related to criterion measures. However, SOM ratios differed dramatically, depending on the attentional focus of thoughts. The findings illustrate types of thoughts which occur during interaction between people with and without disabilities, demonstrate a simple technique for grouping thoughts into valenced categories on an empirical basis, and highlight the relative contribution of cognitive and affective elements to overall valenced scores. Implications for research on assessment of self-statements are discussed and recommendations are made concerning programming to facilitate the social integration of people with disabilities.This research was supported by grants to the first author from the Social Sciences and Humanities Research Council of Canada and from Fonds F.C.A.R. pour l'aide et le soutien à la recherche. Thanks are due to Meribah Aikens, Maria Barile, Leo Bissonette, Bosco Daude, Jim Dubois, Lillian Fox, Evelyn Gold, Naomi Goodz, Darlene Judd, André Leblanc, John Martos, Sue McKenzie, Irwin Slopak, and Joan Wolforth for their assistance with various stages of this investigation.