Destruction of WiDr multicellular tumor spheroids with the novel thymidylate synthase inhibitor 1843U89 at physiological thymidine concentrations

The activity of a novel thymidylate synthase inhibitor, 1843U89, against WiDr human colon carcinoma multicellular tumor spheroids was investigated. Continuous exposure of the spheroids to 3 nM 1843U89 for 10 days resulted in spheroid disruption, whereas 100 nM methotrexate (MTX) was required for similar effects. Short-term treatment experiments demonstrated that a 3-day exposure to 100 nM 1843U89 caused spheroid disruption 9 days after drug removal. A 4-day exposure to 10 nM 1843U89 caused spheroid disruption 8 days after drug removal. In contrast, treatment with 10 or 100 nM 1843U89 for 6–48 h or treatment with 1 nM 1843U89 for up to 5 days caused only growth delay. Continuous exposure of spheroids to 30 nM 1843U89 in the presence of 0.05–0.3 M thymidine was as effective in causing spheroid disruption as treatment in the absence of thymidine, but treatment in the presence of 0.7–3.0 M thymidine caused partial reversal of spheroid disruption. The results of these experiments suggest that 1843U89 should have potent solid tumor activity in humans but should be less effective in mice due to differences in circulating thymidine levels (0.1 vs 1 M, respectively).     

Elephant people: the phenomena of social withdrawal and self-imposed isolation of people dying with AIDS

The phenomena of self-initiated isolation and social withdrawal of people dying from AIDS is described and explained in the context of its irony and detriment to the patients' well being, minimizing access to social support resources. The psychological and the therapeutic relevance of social support during the critical transition phase is explored. Recommendations for curbing the phenomena of self-imposed social death in PWAs, as well as suggestions for future research on the value of psychosocial support to the PWA's well being during the transition phase, are also discussed.     

Descending thoracic aortobifemoral bypass: an alternative approach for difficult aortic revascularization

Descending thoracic aortobifemoral bypass is an alternative inflow operation in cases in which standard aortobifemoral or axillobifemoral bypass is not an option. We performed descending thoracic aortobifemoral bypass for failed inflow operations in four patients, prior abdominal/pelvic radiation in two patients, poor quality distal aorta (extensive atherosclerotic disease or poor tissue quality) in two patients, and abdominal sepsis in two patients. Eight have had excellent results with patency at a mean follow-up of 38 months. There was no limb loss. One patient died of organ failure, and one patient with hypercoagulability developed a graft clot. A literature review disclosed that a descending thoracic aortobifemoral bypass was reported to have been performed in 203 patients, with most cases reported in the last decade. This procedure was the primary inflow operation in 42 per cent of cases. Indications for the operation included failed aortic grafts (38%), "hostile" abdomen (21%), infected aortic grafts (18%), and other (23%). The patency rate was 95 per cent at 6 months. Few long-term results are known, but the results appear to be durable. Descending thoracic aortobifemoral bypass is a useful operation in highly selected circumstances in which conventional methods of aortic reconstruction are not available.     

Improved management of infrainguinal bypass graft infection with methicillin-resistant Staphylococcus aureus

BACKGROUND: There is considerable debate over the management of infected infrainguinal grafts. This report describes recent experience in this field and documents the change in clinical practice needed to deal with methicillin-resistant Staphylococcus aureus (MRSA). METHODS: All infected infrainguinal grafts between January 1991 and July 1997 were reviewed. In the light of the findings, clinical practice was modified considerably. A further 1 year was audited prospectively up to August 1998. RESULTS: Twenty-six patients were treated for 27 infrainguinal graft infections (25 prosthetic, two vein). Twenty were treated by complete graft excision as the initial therapy; graft preservation was attempted in six patients. Before 1995, the infecting organisms were predominantly Pseudomonas aeruginosa or methicillin-sensitive staphylococci. Subsequently all 14 patients treated up to 1997 had infection with MRSA. The overall amputation rate was 17 of 26; ten amputations were in patients with MRSA. Four patients died, all with MRSA sepsis. As a result of this experience a policy of complete isolation was adopted for all patients infected with MRSA. In the 12 months since this policy was introduced, 77 infrainguinal grafts (61 vein, 16 prosthetic) have been inserted. Two grafts (3 per cent) have become infected, necessitating graft excision and amputation. CONCLUSION: MRSA infection of an infrainguinal graft is a serious complication with high associated amputation and mortality rates. Isolation and barrier nursing appeared to contain the problem.     

Intestinal obstruction from midgut volvulus after laparoscopic cholecystectomy

Congenital midgut malrotation, a rare anatomic anomaly that can lead to duodenal or small bowel obstruction, rarely is recognized beyond the first year of life. We report a case of unrecognized congenital midgut malrotation that resulted in midgut volvulus, causing intestinal obstruction and requiring emergent reoperation after laparoscopic cholecystectomy. This unusual complication, first reported in 1994, involved a 56-year-old man and resulted in cecal infarction recognized and treated on the second postoperative day. This second case describes a less acute postoperative course, with multiple bouts of partial bowel obstruction leading to two readmissions and finally resulting in a reexploration and definitive treatment on the 19th postoperative day. Received: 16 February 1999/Accepted: 22 March 1999     

Improvement of pressure flow parameters with finasteride is greater in men with large prostates. Finasteride Urodynamics Study Group

PURPOSE: We assess the effect of finasteride, a 5alpha-reductase inhibitor, on objective voiding parameters in men with lower urinary tract symptoms and benign prostatic enlargement on digital rectal examination (known as clinical benign prostatic enlargement) in a double-blind placebo controlled multicenter study using strict standard pressure flow study techniques. MATERIALS AND METHODS: A modification of the Abrams-Griffiths nomogram was used by 1 reader to ensure that all patients met objective criteria for bladder outlet obstruction at baseline. After performing a pressure flow study patients with obstruction were randomized 2:1 to receive 5 mg. finasteride (81) or placebo (40) daily. A second pressure flow study was performed at month 12. At baseline and month 12 free urinary flow studies and transrectal ultrasound were performed, and International Prostate Symptom Score questionnaires were completed. Patients were treated between May 1994 and July 1996. RESULTS: Finasteride caused a significant decrease (-8.1 cm. water) in detrusor pressure at maximum flow (p <0.05 versus placebo p = 0.02), increase (+1.1 ml. per second) in maximum flow rate (p <0.05 versus placebo p = 0.02) and decrease (-22.8%) in prostate volume (p <0.05 versus placebo p <0.001). Men with prostates larger than 40 cc had greater improvement in detrusor pressure at maximum flow (between group difference -14.5 cm. water, 95% confidence interval -26.2 to -2.6, p = 0.02) and maximum flow rate (mean treatment effect +1.6 ml. per second, 95% confidence interval -0.2 to 3.0, p = 0.02) compared to those with prostates 40 cc or less (between group differences not significant). CONCLUSIONS: Finasteride treatment resulted in improvements in urodynamic parameters, which were greater in men with large prostates.     

Discriminating mirror symmetry in foveal and extra-foveal vision

The ability to discriminate perfect from imperfect mirror symmetry was examined at the fovea and at eccentricities out to 10 degrees in the nasal visual field. A 2-AFC method of constant stimuli was employed in which a bilaterally symmetric pattern was presented in one interval and a degraded version of this symmetric pattern in the other. The subject's task was to decide which interval contained the perfectly symmetric pattern. Pattern size was varied by changing the viewing distance. Probit analysis revealed the degree of asymmetry corresponding to 75% correct performance. Given sufficient size scaling, perfectly symmetric stimuli can be discriminated from degraded symmetric stimuli in extra-foveal vision. Spatial scaling with an E2 value similar to that for positional acuity was successful in removing the eccentricity dependence for the task.