A trial of prophylactic thiotepa or mitomycin C intravesical therapy in patients with recurrent or multiple superficial bladder cancers

There were 40 consecutive patients with recurrent or multiple superficial stage Ta or T1 transitional cell cancer assigned randomly to receive prophylactic thiotepa or mitomycin C intravesical chemotherapy. Patients received 8 weekly instillations followed by 22 monthly treatments of either 60 mg. thiotepa or 40 mg. mitomycin C. Of 25 patients randomized to receive mitomycin C 4 had recurrence in a total of 337 patient-months (1.19 per 100 patient-months), while disease recurred in 1 of 15 patients randomized to receive thiotepa who were followed for a total of 220 patient-months (0.45 per 100 patient-months). No significant difference in recurrence rate was noted for either drug group (p equals 0.18). Toxicity requiring cessation of therapy was observed in 7 patients (28 per cent) on mitomycin C and none on thiotepa.     

Cloacal exstrophy: individualized management through a staged surgical approach

Cloacal exstrophy, centered on the maldevelopment of the primitive streak mesoderm and cloacal membrane, results in bladder and intestinal exstrophy, omphalocele, gender confusion, and hindgut deformity. The surgical management and outcome of 10 of 14 survivors (1965 to 1988) are described. Genotypic males (6) were assigned male (2) or female (4) phenotype. Genotypic females (4) were unchanged. All had omphalocele closure in the newborn period. Two had loop stomas. Eight had end stomas (ileostomy [6], ileocolostomy [2]). Toddler and adolescent reconstruction differed in each. Early in the study, abdominoperineal pull-through failed in four patients, necessitating permanent stoma. Four patients had a stoma from the outset. Augmentation using colon remnant improved water loss and nutrition in two infants. Exstrophy turn-in for urinary reservoir was considered in all, but was impossible in three who required urinary diversion. Six patients had exstrophy turn-in and now void by clean intermittent catheterization (4), continent vesicostomy (1), and incontinent (1). Hindgut augmentation improved urinary capacity in two. Two genotypic-phenotypic males had penile lengthening. Four genotypic male-phenotypic females had early orchiectomy with subsequent clitoroplasty or vaginoplasty. Four genotypic-phenotypic females had clitoroplasty or vaginoplasty. Cloacal exstrophy is compatible with a useful life and sound psychologic development, but requires staged reconstruction with long-term support and follow-up.     

Phase II evaluation of merbarone in renal cell carcinoma

Summary The Southwest Oncology Group (SWOG) studied the response rate and toxicity of merbarone (1,000 mg/m² IV continuous infusion days 1–5, q 21 days) in patients with advanced metastatic renal cell carcinoma. Among 36 eligible patients, there was one partial response for a response rate of 3% (95% C.I. 0.1–15%). There were no mixed responses. There were no treatment related deaths or adverse drug reactions. Significant anemia, diarrhea, and hypercalcemia were observed. Mild to moderate degrees of malaise/fatigue/lethargy, dizziness/vertigo, hyperglycemia, creatinine increase, nausea, vomiting, weight loss, pedal edema, dyspnea, and granulocytopenia were noted. Merbarone does not have significant activity as a single agent in advanced renal cell carcinoma.     

The failure of infarction and/or nephrectomy in stage IV renal cell cancer to influence survival or metastatic regression

The success of cancer therapy depends on the destruction of all viable cancer cells in the primary site, as well as in metastatic areas. Surgery alone can do little for the patient whose tumor has produced distant involvement except in those situations where surgical excision, radiotherapy, chemotherapy, or immunotherapy can be relied on to eradicate metastatic disease. Because of the paucity of systemic therapy for renal cell carcinoma, an aggressive surgical approach to the primary tumor is justifiable when all metastatic lesions can be excised or otherwise definitively treated and in experimental protocols in which adjuvant therapy of possible benefit can be combined with palliative nephrectomy. There is no evidence, however, in reported studies to suggest that routine palliative nephrectomy in patients who will not be offered adjuvant systemic therapy or radiation is beneficial. Such practice is also associated with a higher incidence of complications and mortality than is expected for resection of localized renal cell carcinoma. For these reasons, it is reasonable to recommend adjunctive nephrectomy only in certain selected instances, which include (1) the control of a patient's current symptoms related to the primary disease, for example, flank pain, hematuria, fever and toxicity, anemia, erythrocytosis, and hypercalcemia; (2) nephrectomy with the excision of a solitary metastasis; and (3) the patient who is willing to undergo experimental therapy, part of which involves removal of the primary tumor.     

Effects of amyotrophic lateral sclerosis serum on cultured chick spinal neurons

We used a quantitative immunoassay to examine the effects of human serum and immunoglobulins on neurofilament protein expression in cultures of chick spinal neurons. Compared with cultures grown in the presence of serum from healthy controls or patients with other neurologic disorders, ALS serum lowered the level of neurofilament proteins. Effects were similar with or without muscle-derived neurotrophic factors; there was no specificity for motor neurons. No neurotoxic activity was found in immunoglobulin fractions, and there was no evidence of circulating antibodies that might neutralize muscle-derived neurotrophic factors or induce cytolysis of spinal neurons.     

Asexual development of Cryptosporidium parvum within a differentiated human enterocyte cell line.

Unremitting diarrhea with malabsorption is associated with Cryptosporidium parvum infection of the small intestine in patients with AIDS. The lack of a well-defined in vitro model of C. parvum infection has severely hampered research into the biology of cryptosporidial invasion of the host epithelial cell and development of new pharmacologic and immunologic therapies. The adherent human intestinal epithelial cell line HT29 when grown in glucose-free medium develops morphologic and functional characteristics of the small intestine enterocyte and was used to develop an in vitro model of infection. Cryptosporidium oocysts obtained from AIDS patients were applied to a monolayer of cloned, differentiated HT29.74 cells. Cells were fixed and stained to estimate the degree of parasite infection. Schizonts were easily distinguished from the host cell by light microscopy. Twenty-four hours after 10(5) oocysts were added to approximately 10(6) HT29.74 cells, Cryptosporidium infection rates varied from 50 to 120 schizonts per 1,000 cells. Among 14 different experiments, the mean infection rate was 91 (+/- 18) schizonts per 1,000 cells. Electron microscopy at 6 and 24 h confirmed intracellular localization and development of schizonts. The morphologic features of the cryptosporidial schizonts within HT29.74 cells, which included the presence of a dense band and feeder layer, were identical to those described during cryptosporidial infection of human enterocytes in patients with AIDS. Fewer schizonts were observed at 5 days and beyond. Infection of differentiated HT29.74 cells (62 and 65 schizonts per 1,000 cells at 24 and 72 h, respectively) was over five times more efficient than infection of undifferentiated HT29.74 cells (9 and 5 schizonts per 1,000 cells at 24 and 72 h, respectively). In vitro infection of differentiated HT29.74 cells will allow a better understanding of the mechanisms by which C. parvum infects the small intestinal epithelium and will allow a systematic evaluation of new therapeutic agents.     

S-nitrosoglutathione-containing hydrogel accelerates rat cutaneous wound repair

BACKGROUND: Nitric oxide (NO) plays a key role in wound repair and S-nitrosothiols like S-nitrosoglutathione (GSNO) are well known NO donors. METHODS: Animals were separated in two groups and submitted to excisional wounds on the dorsal surface at the first day. GSNO (100 microm)-containing hydrogels were topically applied on the wound bed in the GSNO group, daily, during the first 4 days. Control group was topically treated with hydrogel without GSNO for the same period. Wound contraction and re-epithelialization were measured. Animals were sacrificed 21 days after wounding. Samples of lesion and normal tissue were formalin-fixed, paraffin embedded for histological analysis. RESULTS: Wound contraction, measured 14 and 21 days after wounding, was greater in the GSNO group than in the control group (P<0.05 for both). The re-epithelialized wound area, measured 14 days after wounding, was higher in the GSNO group than in the control group (P<0.05). A higher amount of inflammatory cells was observed in superficial and deep areas of the granulation tissue of the control group compared to the GSNO group. Twenty-one days after wounding, thin red-yellow collagen fibers arranged perpendicularly to the surface were found in the granulation tissue of the control group, whereas in the GSNO-treated group collagen fibers were thicker and arranged parallel to the surface. Increased number of mast cells was observed in the GSNO group compared with that in the control group. Vascularization and myofibroblast distribution were similar in both groups. CONCLUSION: Topical application of GSNO-containing hydrogel during the early phases of rat cutaneous wound repair accelerates wound closure and re-epithelialization and affects granulation tissue organization.     

Prevalence and incidence of HIV among incarcerated and reincarcerated women in Rhode Island

This study explores recent temporal trends in HIV prevalence among women entering prison and the incidence and associated risk factors among women reincarcerated in Rhode Island. Results from mandatory HIV testing from 1992 to 1996 for all incarcerated women were examined. In addition, a case control study was conducted on all seroconverters from 1989 to 1997. In all, 5836 HIV tests were performed on incarceration in 3146 women, 105 of whom tested positive (prevalence, 3.3%). Between 1992 and 1996, the annual prevalence of HIV among all women known to be HIV-positive was stable (p = .12). Age >25 years, nonwhite race, and prior incarceration were associated with seropositivity. Of 1081 initially seronegative women who were retested on reincarceration, 12 seroconverted during 1885 person-years (PY) of follow-up (incidence, 0.6/100 PY). Self-reported injection drug use (IDU; odds ratio [OR], 3.7; 95% confidence interval [CI], 1.3-10.1) was significantly associated with seroconversion, but sexual risk was not (OR, 1.1; 95% CI, 0.4-3.5). Incarceration serves as an opportunity for initiation of treatment and linkage to community services for a population that is at high risk for HIV infection.