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     

Cancer mortality among northern Georgia carpet and textile workers

Proportionate cancer mortality was analyzed among white male carpet and textile workers in five northwest Georgia counties for the years 1970-1984. Compared with other Georgians, carpet and textile workers had higher proportions of lymphocytic leukemia (proportionate cancer mortality ratio [PCMR] = 2.9; 95% CI = 1.4-5.4]) and testicular cancer (PCMR = 3.2; 95% CI = 1.0-7.5). The excess mortality from lymphocytic leukemia was even higher when the analysis was limited to workers deemed most likely to work directly in production areas (PCMR = 4.2; 95% CI = 1.7-8.7). Further studies are needed to determine if the observed excesses are the result of workplace exposures.     

The short-term stability of student ratings of instruction in medical school

The purpose of this study was to assess the degree of consistency in student ratings of teacher effectiveness during the first year of medical school. Student ratings of teaching effectiveness represent a commonly used source of information that enters into the academic decision-making process. In medical school, student evaluations often represent a major source of information that is used in promotion and tenure decisions. It is essential that the precision of such ratings be ascertained so that decision-makers will know how much confidence to place in this source of information on teaching effectiveness. In this study, each member of a first-year medical school class was randomly assigned a two-digit identification number at the beginning of the spring semester, 1986. As the semester progressed students were asked to evaluate each full-time teacher in three major courses. Multiple instructors were utilized in each course (n = 10). Each teacher was evaluated immediately after lectures during the first (T1) and second (T2) halves of the course. Students evaluated the teacher a third time (T3) as part of the end-of-semester overall course evaluation. The teachers were evaluated on a short eight-item Likert-type scale that identified several key indicators of effective teaching. Students attached their anonymous identification numbers to individual ratings so that their responses could be matched in the analysis. The results indicate that medical students are only moderately consistent in the extent to which they evaluate teachers. This inconsistency varied by course and by instructors within courses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Andrology: Transrectal electroejaculation in combination with in-vitro fertilization: an effective treatment of anejaculatory infertility after testicular cancer

Treatment of non-seminomatous testicular cancer often leadsto infertility due to anejaculation/retrograde ejaculation andpoor sperm quality. In these men spermatozoa may be obtainedby transrectal electroejaculation (TE), but the optimal strategyfor assisted procreation in these couples is not known. Ouraim was to examine whether TE and conventional in-vitro fertilization(IVF) would be successful. A total of 10 couples, with long-standinginfertility due to anejaculation or retrograde ejaculation aftertreatment for testicular cancer 5–14 years earlier, werereferred to our unit. All men underwent diagnostic TE undergeneral anaesthesia. Spermatozoa were recovered in nine cases.The antegrade fraction was prepared and used for IVF. Spermquality was variable and conventional IVF was considered impossiblein three cases. Altogether six IVF treatment cycles in six couplesresulted in five pregnancies, of which four resulted in a deliveryand one resulted in a spontaneous abortion. One additional pregnancyis ongoing after transfer of cryopreserved embryos. The fertilizationrate was 54% (33/61) and the cleavage rate was 97% (32/33).No complications relating to the procedure have been encountered.     

Periodontal conditions among the middle-aged and the elderly in Hong Kong

Abstract The aim of this study was to describe the periodontal conditions in 372 35–44-yr-old and 537 noninstitutionalized 65–74-yr-old Hong Kong Chinese who were examined clinically for loss of attachment, recession, probing depth, calculus, and bleeding after probing. Community Periodontal Index (CPI) data and treatment need indications were compiled from index teeth or their substitutes. The prevalence of loss of attachment varied considerably in both cohorts according to the definition of the threshold (≥6, ≥9, and ≥12 mm, respectively). The mean numbers of teeth with loss of attachment at the ≥6-mm threshold and at higher thresholds were small. In both age cohorts, about one-fifth of subjects had probing depths ≥6-mm, while al the ≥9-mm threshold only 2–3% were so affected. Although recession was an important component of loss of attachment in the younger cohort, in the older cohort the prevalence and extent of recession were greater than for probing depths at thresholds ≥4 mm. All subjects had one or more teeth with calculus, bleeding, or both, most teeth being so affected. Eighty-four of the 537 65–74-yr-old subjects were excluded either because of edentulousness or because extractions indicated for the remaining teeth would have rendered the subjects edentulous. The distribution of subjects according to their highest CPI score was remarkably similar for the two cohorts. No subjects in either age group were assessed as “healthy” (CPI code 0) or had “bleeding only” (code 1) as their highest score. While most subjects scored CPI code 2 or 3 us their highest score, only 17% of the younger and 15% of the older cohort scored Community Periodontal Index of Treatment Needs (CPITN) code 4. Differences in the mean number of sextants affected by CPI codes between the two cohorts were mainly due to a greater number of excluded sextants in the older cohort. CPI findings for 35–44-yr-olds differed little from those reported in 1984.     

Morphological types of ganglion cells in the dog and wolf retina.

The morphological types of ganglion cells in the dog and wolf retina were studied by intracellular staining with Lucifer Yellow. These retinae contain a range of ganglion cell types that closely correspond to those found in cat retina: alpha cells with large somata and large, relatively densely branched dendritic trees; beta cells with medium-sized somata and small, densely branched dendritic trees; and a variety of other types with smaller somata and varying dendritic branching patterns and dendritic field sizes. The correspondence of canine and cat ganglion cell types strengthens the view that there is a common set of ganglion cell types in carnivores. Alpha and beta cell dendritic trees of dog and wolf are monostratified in either the inner or the outer part of the inner plexiform layer, suggesting an on/off dichotomy in the response to light. Dendritic field sizes of dog alpha and beta cells increase from the central area to peripheral retina: alpha cell fields from 160-200 microns to about 1,100 microns diameter, and beta cell fields from 25 microns to about 360 microns diameter. These sizes are quantitatively very similar to those found in cat retina. The close qualitative and quantitative morphological correspondence of cat and dog ganglion cells suggests that they are also functionally very similar. It is likely that dog alpha cells have brisk-transient (Y), and dog beta cells brisk-sustained (X) concentric receptive fields. From the smallest beta cell sizes it is concluded that the visual acuity of the dog may be as good as that of the cat.     

Influences of context on early writing development

Research on children's early writing development in the past has focused primarily on product and process. In reviewing the more recent research on early writing development, however, a new focus of context emerges. Occurrences of literacy are now being observed in the home, the school, and the community. With this new emphasis, comes the task of defining context. A definition of context reflects theoretical perspectives, areas of research interests, and types of methodologies employed in conducting research. Therefore, the purpose of this article is to address the following aspects of context: #op1#cp multidiscipline perspectives and definitions of context, #op2#cp contextual shifts observed between the home and the school, #op3#cp contextual factors present when learning how to write, and #op4#cp pedagogical implications for curriculum development.     

Experimental studies of chemosensitivity testing of urothelial cancer grown in nude mice

Summary The present study provides information relevant to a number of variables which may influence response to treatment of nude mouse-grown human urothelial cancer. A number of xenotransplanted tumors were exposed to selected treatments at different transplant generations, and at various dose levels and treatment schedules. It was observed that nude mouse-grown tumors were characterized by consistency, reproducibility and biological stability not affected by the transplant generation at which they were examined. Treatment related dose response curves were steep, the sharpness of the curves depending on the degree of tumor sensitivity. Best therapeutic results were obtained at the maximum tolerated dose of cytotoxic agents under study and of importance, a 20% to 40% dose reduction with the same treatment schedule resulted in little or no activity. In addition, treatment schedule, timing and sequence of treatments and to a certain degree, tumor grade were important variables which could influence tumor response. The nude mouse-human tumor system provides important preclinical guidelines on dose, schedule, sequence and timing of treatments and can assist in designing more efficient clinical trials.     

Surface behavior of axolemma monolayers: Physico-chemical characterization and use as supported planar membranes for cultured Schwann cells

The axolemma membrane forms a stable and reproducible monomolecular layer at the air-aqueous interface. The major lipids and proteins are present in this monolayer in molar ratios similar to the original membrane. Acetylcholinesterase and Na-K-ATPase activities are preserved in the monolayer to levels of 64% and 25%, respectively. The total lipid fraction forms a homogeneously mixed phase. The presence of proteins in the monolayer introduces surface inhomogeneties. Among other features, this is revealed by the presence of two values of lateral pressure at which the monolayer shows partial or total collapse: a broad partial collapse at surface pressures between 13 to 30 mN/m and a sharp collapse point at 46 mN/m. The average molecular areas, the broad collapse point, and the variation of the surface potential per molecule suggest the relocation of protein components at surface pressures between 13 to 30 mN/m. The behavior is consistent with the extrusion and exposure of proteins toward the aqueous medium that depends on the lateral pressure. Schwann cells grown on coverslips coated with axolemma monolayers at 13 mN/m (beginning of the broad collapse) and 34 mN/m (above the broad collapse) recognize the difference in the surface organization of axolemma caused by the lateral pressure which affects their proliferation, morphology, and spatial pattern of organization. Our results show for the first time that response of Schwann cells depends on the intermolecular organization of the axolemma surface with which they interact. These results suggest that the local expression of putative surface molecules of axolemma that may mediate membrane recognition and the signalling of morphological and proliferative changes can be modulated by long range supramolecular properties. © 1993 Wiley-Liss, Inc.