A model of human melanoma in cyclosporine-immunosuppressed rats

A human malignant melanoma maintained in athymic nude mice has been successfully implanted and grown in cyclosporine (Cys)-immunosuppressed Lewis rats. Suspended melanoma cells (10(6)) or solid tumor sections measuring 2-4 mm in diameter were implanted s.c. in rats receiving parenteral Cys doses of 15-50 mg/kg each day for 1 week, and 3 times per week thereafter. Eighty-five percent of solid tumor sections implanted in animals receiving 25 mg/kg resulted in tumor growth, whereas no tumors grew from cell suspension injection sites. The average maximum tumor growth rate was 2 cm3/day, with a doubling time of 8 days. Tumors retained pretransplant gross and microscopic morphology, karyotype, and labeling index. Possible advantages of this model over the athymic nude mouse include greater longevity, larger animal and tumor size, and less stringent aseptic environmental requirements. This model may prove useful for further study of the pathophysiology of melanoma and for testing of new antimelanoma therapies.     

Pseudomonas aeruginosa serotype 0:9. New cause of whirlpool-associated dermatitis

In a five-day period, dermatitis developed in nearly one fourth of the guests staying at a large Georgia hotel. Dermatitis was associated with use of the hotel's whirlpool (p less than 0.001) and indoor swimming pool (p less than 0.001). Attack rates were highest among persons more frequently exposed to the whirlpool, in persons under 10 years of age, and during periods of heaviest bather load. Pseudomonas aeruginosa was isolated from skin lesions of 13 of 20 patients from whom culture specimens were taken. Ten isolates were serotype 0:9. The whirlpool's water grew P. aeruginosa serotype 0:9; however, the whirlpool's automatic chlorinator was functioning properly, the pH of the water was 7.2, and the free chlorine level was 0.6 mg/liter. This is the first report of a whirlpool-associated outbreak caused by P. aeruginosa serotype 0:9. Our findings suggest that this strain may not be readily sensitive to recommended chlorine concentrations.     

Outcome of allogeneic stem cell transplantation for B cell chronic lymphocytic leukemia

The objective of this study was to describe the outcome of allogeneic stem cell transplantation (alloSCT) in a series of patients with B cell chronic lymphocytic leukemia (B-CLL). Twenty-three B-CLL patients were transplanted between 1988 and 1997 using stem cells from a related (n = 20) or an unrelated donor (n = 3). The median age of the patients was 46 years, and the median number of prior chemotherapy regimens received was two. At transplantation, 14 patients had chemorefractory disease and 12 of these were refractory to fludarabine. The preparative regimens included total body irradiation (TBI) in 22 of the 23 cases. All patients received graft-versus-host disease (GVHD) prophylaxis with cyclosporine and methotrexate. Twenty patients (87%) achieved a complete remission (CR). The incidence of grade II-IV acute GVHD was 54%. Fourteen (61%) patients are alive and disease-free, including two with unrelated donors, at a median of 26 months (range, 9-115 months). Nine patients (39%) have died, one of whom had progressive B-CLL. The only favorable prognostic factor for failure-free survival (FFS) and overall survival (OS) after alloSCT was the use of a cyclophosphamide/TBI rather than an etoposide/cyclophosphamide/TBI regimen (P = 0.03). The projected 5-year FFS, OS, and relapse rates after alloSCT were 65% (95% CI, 48-88%), 62% (95% CI, 43-88%), and 5% (95%, CI 0-13%), respectively. These findings demonstrate the potential of high-dose therapy and alloSCT for inducing and maintaining a remission in patients with advanced or chemorefractory B-CLL. The low relapse rate may be due to an allogeneic graft-versus-leukemia effect.     

Long-term mortality and morbidity of transfusion-associated non-A, non-B, and type C hepatitis: A National Heart, Lung, and Blood Institute collaborative study

Persons with non-A, non-B hepatitis (cases) identified in 5 transfusion studies in the early 1970s have been followed ever since and compared for outcome with matched, transfused, non-hepatitis controls from the same studies. Previously, we reported no difference in all-cause mortality but slightly increased liver-related mortality between these cohorts after 18 years follow-up. We now present mortality and morbidity data after approximately 25 years of follow-up, restricted to the 3 studies with archived original sera. All-cause mortality was 67% among 222 hepatitis C-related cases and 65% among 377 controls (P = NS). Liver-related mortality was 4.1% and 1.3%, respectively (P =.05). Of 129 living persons with previously diagnosed transfusion-associated hepatitis (TAH), 90 (70%) had proven TAH-C, and 39 (30%), non-A-G hepatitis. Follow-up of the 90 TAH-C cases revealed viremia with chronic hepatitis in 38%, viremia without chronic hepatitis in 39%, anti-HCV without viremia in 17%, and no residual HCV markers in 7%. Thirty-five percent of 20 TAH-C patients biopsied for biochemically defined chronic hepatitis displayed cirrhosis, representing 17% of all those originally HCV-infected. Clinically evident liver disease was observed in 86% with cirrhosis but in only 23% with chronic hepatitis alone. Thirty percent of non-A, non-B hepatitis cases were unrelated to hepatitis viruses A,B,C, and G, suggesting another unidentified agent. In conclusion, all-cause mortality approximately 25 years after acute TAH-C is high but is no different between cases and controls. Liver-related mortality attributable to chronic hepatitis C, though low (<3%), is significantly higher among the cases. Among living patients originally HCV-infected, 23% have spontaneously lost HCV RNA.     

Low-molecular-weight heparins in ischemic heart disease

PURPOSE OF REVIEW: The objective of this review was to summarize the recent developments regarding the use of low-molecular-weight heparins in the management of acute coronary syndromes. RECENT FINDINGS: In the setting of unstable angina and non-ST-elevation myocardial infarction, enoxaparin is superior to unfractionated heparin in reducing death, myocardial infarction, and recurrent ischemia both in the short-term and to 1 year. However, this does not necessarily imply a class effect of low-molecular-weight heparins in general. When combined with glycoprotein IIb/IIIa inhibitors, enoxaparin appears to be effective and safe even for patients treated according to an early invasive strategy. In patients receiving fibrinolytics for ST-elevation myocardial infarction, low-molecular-weight heparins are as effective as unfractionated heparin in maintaining patency of the infarct-related artery and in reducing the composite endpoint of death and reinfarction. However, serious bleeding is more common, especially among the elderly, and the optimal dosing regimen in ST-elevation myocardial infarction remains to be defined. SUMMARY: Low-molecular-weight heparins are safe and effective in the management of unstable angina and non-ST-elevation myocardial infarction, with or without concurrent administration of glycoprotein IIb/IIIa inhibitors. Ongoing studies will clarify the role of low-molecular-weight heparins as adjunctive therapy for fibrinolysis.