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     

Comparison between testosterone oenanthate-induced azoospermia and oligozoospermia in a male contraceptive study. IV. Suppression of endogenous testicular and adrenal androgens

Administration of supraphysiological doses of testosterone to normal men causes inhibition of spermatogenesis, but while most become azoospermic, 30-55% maintain a low rate of spermatogenesis. We have investigated whether there are differences in endogenous androgen production, of testicular and adrenal origin, which may be related to the degree of suppression of spermatogenesis. Thirty-three healthy Caucasian men were given weekly i.m. injections of 200 mg testosterone oenanthate (TE), 18 became azoospermic, while 15 remained oligozoospermic. Urinary excretion of epitestosterone, a specific testicular product, was reduced to <10% of pretreatment values, with no differences between the groups. Similar results were obtained for other markers of testicular steroidogenesis. Urinary and plasma adrenal androgens were also reduced during TE treatment: a statistically significant decrease in both (P < 0.001 and P < 0.05 respectively) was seen in the azoospermic but not oligozoospermic responders. These results suggest that testicular steroidogenesis is decreased to <10% by the administration of supraphysiological doses of exogenous testosterone. Differences in the degree of ongoing steroidogenesis in the testis do not appear to account for incomplete suppression of spermatogenesis, thus differences in androgen metabolism may underlie this heterogeneous response. A small but significant reduction in secretion of adrenal androgens was also detectable, the relevance of which is unclear.      

An analysis of the association of American medical colleges' review of minorities in medical education

The Association of American Medical Colleges publishes an enormous database each year, which encompasses every conceivable category of medical education. This information covers high-school student premedical activities, medical school/student data, demographics of residents and fellows in training, a profile of medical school faculty according to academic rank and the enrollment of each medical school in the country. It is all categorized according to race, ethnicity and gender. Furthermore, it is a longitudinal survey and, therefore, valid comparisons can be made over long periods of time. The extensive coverage of African-American involvement in the system at all levels allows for healthcare planners, administrators, politicians and students/parents at all levels to use this as a roadmap for planning purposes. Much of the data is broken down according to individual states, thus enabling students to make better decisions about selecting private versus public institutions for their training. The data on residents in training and medical school faculty provides very useful information for healthcare planners, state and federal government officials, and medical school deans and university administrators interested in addressing diversity issues within their respective domains.     

Postnatal growth of lung parenchyma in the piglet: Morphometry correlated with mechanics

Background: A previous study of piglet lung growth (Mansell et. al. 1989. J. Appl. Physiol., 67:1422–1427) showed transient stiffness to changes in shape and volume immediately after birth. Later, elastic recoil was found to increase as the lung grew in weight and volume. The present study uses morphometry to test possible structural correlates of these two mechanical changes. Methods: Piglet lungs were fixed near full inflation via the airways during the immediate newborn period (6–12 hours, n=3), at 3–5 days (n=6), 25–30 days (n=5), and 80–85 days (n=3). Morphometry comprised arithmetic and harmonic mean thicknesses of alveolar septae and average mean surface curvature. Measurements of curvature and airspace volume were combined to differentiate alveolar expansion from septal proliferation as mechanisms for volumetric growth. Results: The unique mechanical behavior of the newborn lungs was associated with relatively thick alveolar septae. Marked thinning of the septae and resolution of the stiffness to shape and volume change had occurred by 3–5 days. An increase in elastic recoil during the first postnatal month was found to be associated with simple airspace expansion. The second and third months were characterized by septal proliferation and increase in arithmetic mean septal thickness but elastic recoil did not increase further. Harmonic mean septal thickness and airspace volume per gram of lung tissue did not change over the course of the study. Conclusions: 1) A relative stiffness to shape and volume change in freshly newborn piglet lung is associated with relatively thick alveolar septal walls; 2) postnatal development of piglet lung parenchyma involves septal lengthening and thinning followed by septal proliferation; 3) the initial phase of septal lengthening, rather than the later phase of septal proliferation, is associated with increase in parenchymal recoil. © 1995 Wiley-Liss, Inc.     

Robotic-Assisted Total Knee Arthroplasty: An Assessment of Content,Quality, and Readability of Available Internet Resources

BackgroundThe use of robotic-assisted total knee arthroplasty (TKA) has significantly increased over the past decade. Internet content is largely unregulated and may contain inaccurate and/or misleading information about robotic TKA. Our goal was to assess the content, quality, and readability of online material regarding robotic-assisted TKA.MethodsWe conducted an internet search for the top 50 web sites from each of the 3 most popular search engines (Google, Yahoo, and Bing) using the search term robotic total knee replacement. Each web site was assessed for content, quality, and readability. Web site quality was assessed utilizing the QUality Evaluation Scoring Tool (QUEST). Readability was assessed utilizing the Simple Measure of Gobbledygook, Flesch-Kincaid Grade Level, and Flesch Reading Ease Formula scores.ResultsGeneral risks of TKA were discussed in 47.2%, while benefits were discussed in 98.6% of all web sites. Inaccurate claims occurred at a significantly higher rate in physician/community hospital sources compared to university/academic web sites (59% vs 28%, P = .045). Web sites from university/academic web sites had the highest QUEST scores, while physician/community hospital sources scored the lowest (16.1 vs 10.6, P = .01). Most web sites were written at a college reading level or higher.ConclusionPatients should be counseled on the largely unregulated nature of online information regarding robotic-assisted TKA. Physicians and hospitals should consider revising the readability of their online information to a more appropriate level in order to provide accurate, evidence-based information to allow the patient to make an informed consent decision.