A phase I/II study of continuous infusion suramin in patients with hormone-refractory prostate cancer : toxicity and response

 Introduction: Suramin is a synthetic polysulfonated naphthylurea which has been used for the treatment of African trypanosomiasis and onchocerciasis, but since the mid-1980s has received attention as a possible antiretroviral and antineoplastic agent. Objective: This clinical trial of suramin was undertaken as a phase I/II study in patients with hormone-refractory prostate cancer, with the hypothesis that the intensity of therapy with suramin could be increased significantly if measures were undertaken to maintain the plasma concentrations of the drug under 300 μg/ml. Methods: We report the clinical results of this trial, wherein patients were treated at three different targeted plasma suramin concentrations (275, 215 and 175 μg/ml) for varying periods of time (2, 4 or 8 weeks), with delivery of the drug by continuous intravenous infusion. Results: The major toxicity observed in this trial was neurologic, consisting of a motor and sensory peripheral neuropathy that resulted in both paresis and paralysis of the limbs. Nearly all of this severe (CTEP grade III, IV) neurologic toxicity was observed in the patients treated at a plasma suramin concentration of 275 μg/ml for 4 or more weeks. A single patient treated at 215 μg/ml for 8 weeks developed moderate (CTEP grade III) proximal lower extremity weakness, and no patient treated at 175 μg/ml developed this toxicity. The second most common toxicity observed was infection of the central venous catheter. The overall response rate for all of the evaluable patients was 17% (13 of 75 patients). In addition, prostate-specific antigen (PSA)-defined responses were observed in six patients receiving therapy at 175 μg/ml, but these responses were confounded by cessation of therapy with flutamide during suramin treatment. Conclusions: In summary, although plasma suramin concentrations were maintained below 300 μg/ml, neurologic toxicity nonetheless occurred with high frequency in patients treated at 275 μg/ml for 4 or more weeks. Therapy at 215 and 175 μg/ml was in general well tolerated, but central venous catheter-related infection, as well as the inconvenience and expense of continuous infusional therapy, make this method of drug delivery impractical. Only moderate antitumor activity was observed during this trial, but it is possible that both continuation of flutamide and flutamide withdrawal during suramin therapy confounded the assessment of suramin’s activity in hormone-refractory prostate cancer. Received: 9 June 1995/Accepted: 18 March 1996     

Dynamic skinfold thickness measurement in infants fed breast-milk, low- or high-sodium formula

A stratified sample of normal infants born at term at Johannesburg Hospital, who attended the hospital for a routine 6-week follow-up visit, were selected to include 43 infants who were exclusively breast-fed, 42 fed a low-sodium formula and 39 fed a high-sodium formula (greater than 10 mmol sodium/l). Dynamic skinfold thickness measurements (DSTM), designed to assess the amount of interstitial fluid, were performed on each infant by the application of a skinfold caliper for a 3-second sampling period at two sites. The curves generated by these applications were recorded and analysed by microcomputer. There were no differences between any of the feeding groups for DSTM measurements of blood pressure suggesting that the range of sodium ingested by these groups of infants had no significant effects on extracellular water content. However, using multiple linear regression, both DSTM and blood pressure were best predicted by body weight and not by age or any other anthropometric measurement. Thus the normal postnatal decrease in extracellular fluid volume and increase in blood pressure appears to be most closely related to an increase in body weight.     

Cholesterol-based personal risk assessment in coronary heart disease

Using data from the National Health and Nutrition Examination Survey (NHANES II) 1976-1980, we demonstrate how cross-sectional total serum cholesterol surveillance data can be used by an individual to assess current and future personal cholesterol risk status. We propose statistical models, based on a person's current measured cholesterol level and the relationship between cross-sectional age and cholesterol percentile estimates, that will allow prediction of future cholesterol levels or the age at which specified cholesterol risk levels will be reached if no cholesterol-altering intervention is taken. These models incorporate the observed variation in the NHANES II data and expected intraperson biological variation and intralaboratory analytical variation. We illustrate the adequacy of the models using data from the longitudinal Framingham Study.     

Troponin T levels in baboons with pig heterotopic heart transplants.

Troponin T levels have been monitored in baboons (n = 8) undergoing pig heterotopic heart transplantation, and correlated with a decrease in graft contractions and graft survival. Pig heart graft survival was from 12 to 139 days (mean 45, median 33), and graft failure was associated with predominant thrombotic microangiopathy and ischemia, with focal hemorrhage, and edema. An increase in troponin T levels 5 to 6 days before graft failure correlated closely with diminished graft contractions. An increase in troponin T was a reliable indicator that graft dysfunction was occurring.     

Complications associated with the use of the GlideScope® videolaryngoscope

PURPOSE: Two cases are presented wherein the GlideScope videolaryngoscope (GVL) facilitated laryngeal exposure and successful endotracheal intubation, but resulted in pharyngeal injury. CLINICAL FEATURES: GlideScope videolaryngoscopy was performed in two female patients, whose airways were anticipated to present difficulties for direct laryngoscopy. In the first case, following induction of anesthesia, moderate difficulty was encountered in directing the endotracheal tube (ETT) into the patient's larynx. In the second case, minimal difficulty with the GVL was experienced, and no problems were identified with airway instrumentation until the drapes covering the patient's face were removed. In both instances, the ETT had passed through the right palatopharyngeal arch, requiring suturing in the first patient, and electrocautery in the second patient. CONCLUSION: There have been no previously published reports of injuries related to GlideScope laryngoscopy, but perforation of the palatopharyngeal arch occurring in two patients demonstrates a rare but potentially important complication of the GVL. Strategies to minimize this complication are considered.     

Evaluating the effectiveness of interventions: exploration of two statistical methods.

Repeated measures designs are often used to evaluate the effectiveness of interventions. In these designs, the outcomes are measured on several occasions before and after implementation of the intervention. Two statistical methods, the repeated measures analysis of variance (RM-ANOVA) and hierarchical linear models (HLM), can be used to analyze the data. The authors provide an overview of the statistical models underlying RM-ANOVA and HLM and discuss the strengths and limitations of each. They propose that the 2 methods are complementary in determining the effectiveness of interventions.     

The contribution of selected anthropometric and physiological variables to 10K performance of wheelchair racers: a preliminary study.

The purpose of this study was to determine the relationship between selected anthropometric and physiological variables and 10K time. Eleven male wheelchair athletes with spinal cord injuries in training for national competition performed continuous progressive exercise tests on a wheelchair ergometer to determine maximal metabolic and cardiorespiratory values. Anthropometric data were also collected. The laboratory data were analyzed for correlation with the best 10K time of each subject during the test period. The subjects averaged 27 min 30 sec for their 10K races, 2.49 L.min-1 for VO2max and 35 percent for maximal gross mechanical efficiency during submaximal exercise. Speed at peak oxygen consumption (r = -0.66), gross mechanical efficiency (r = -0.56), and body density (r = -0.57) was found to be significantly (p less than 0.10) correlated with 10K time. The results show very little correlation between VO2max and 10K time (r = 0.02). Further study is indicated for the relationship between gross mechanical efficiency, speed at maximal oxygen consumption, body density, and 10K time; these variables may be useful in evaluating training programs for improving race performance.