Effects of sulodexide in patients with type 2 diabetes and persistent albuminuria.

BACKGROUND: Urinary albumin excretion frequently persists in diabetic patients who are treated with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Sulodexide, a glycosaminoglycan mixture of 80% heparan sulfate and 20% dermatan sulfate, has been hypothesized to reduce persistent albuminuria. We have conducted a multi-center randomized double-blind pilot study in order to determine the effect of 6 months' therapy with sulodexide on urinary albumin excretion and to address logistical issues for a full-scale trial. METHODS: A total of 149 patients with type 2 diabetes and an albumin:creatinine ratio (ACR) between 20 and 300 mg/g were randomized with equal allocation to either placebo, 200 mg of sulodexide or 400 mg of sulodexide. The primary endpoint was the achievement, at 6 months, of either 3(1) return to normoalbuminuria (ACR < 20 mg/g with a decrease of at least 25%) or (2) a decrease in ACR of at least 50% from the baseline value. All patients used a maximum tolerated recommended FDA approved dose of an ACEI or ARB for at least 60 days and had stable blood pressure prior to randomization. RESULTS: The primary efficacy endpoint was achieved in 25.3% of the patients in the two sulodexide groups combined versus 15.4% of the placebo-treated patients (P = 0.26). The primary endpoint was achieved in 33.3% (P = 0.075 for the comparison to placebo) in the sulodexide 200 mg group and 18.4% (P = 0.781) in the sulodexide 400 mg group. (No consistent patterns of side effects were observed. CONCLUSION: Based on the experience gained in this pilot study, one full-scale trial is currently being conducted to evaluate the effects of sulodexide on change in ACR in patients with persistent microalbuminuria, and a longer-term trial is underway to evaluate the effects of sulodexide on long-term renal disease progression in patients with overt proteinuria.

A novel model of HPV infection in meshed human foreskin grafts.

The present study describes a novel meshing procedure that provided successful low-risk papillomavirus propagation and reproducible wart induction in human foreskin xenografts. The initial HPV6 and/or 11 inocula were collected from clinically excised human wart tissues and confirmed to be free of HPV16, 18 and 31 by PCR analysis. Human foreskin grafts were collected from a circumcision clinic, and pre-inoculated with HPV virions by scarification. Meshing was carried out with a Zimmer Skin Grafter Mesher. Grafts were cut to appropriate size (1cm x 1cm or 5mm x 5mm) for cutaneous or subcutaneous grafting to NIH-nu-bg-xid mice under halothane anesthesia. Cutaneous xenografts were dressed with antibiotics and protective band-aids for 3 weeks. In the paralleled experiment using the same viral stock containing both HPV6 and 11, and matched grafts, no visible papillomas were observed in non-meshed cutaneous xenografts (n = 4 up to 6 months). In comparison, six of eight cutaneous xenografts treated with the meshing procedure formed visible papillomas within 4 months. This high frequency of distinct papilloma induction over the surface of meshed xenografts were reproduced in subsequent experiments with viral stocks containing both HPV11 and 6 (8 out of 10 grafts), or with a single-type HPV11 inoculum (80-100%). In contrast, an initial viral stock of single-type HPV6 provided lower frequency and more delayed papilloma induction. Serial passage of HPV6 in the meshed xenograft appeared to improve both the induction frequency and growth rate up to the 3rd generation. Histology, in situ hybridization, and immunohistochemical analysis revealed similarity of xenograft warts to those observed in the clinic. The highly reproducible papilloma induction rate and successful viral stock propagation associated with the meshing procedure provide a novel feature in the HPV xenograft model.

Unpacking cultural factors in adaptation to type 2 diabetes mellitus.

BACKGROUND: Race and ethnicity are used as predictors of outcome in health services research. Often, however, race and ethnicity serve merely as proxies for the resources, values, beliefs, and behaviors (ie, ecology and culture) that are assumed to correlate with them. "Unpacking" proxy variables-directly measuring the variables believed to underlie them-would provide a more reliable and more interpretable way of looking at group differences. OBJECTIVE: To assess the use of a measure of ecocultural domains that is correlated with ethnicity in accounting for variance in adherence, quality of life, clinical outcomes, and service utilization. DESIGN: A cross-sectional observational study. PARTICIPANTS: Twenty-six Hispanic and 29 non-Hispanic white VA primary care patients with type 2 diabetes mellitus. MEASURES: The independent variables were patient ethnicity and a summed score of ecocultural domains representing patient adaptation to illness. The outcomes were adherence to treatment, health-related quality of life, clinical indicators of disease management, and utilization of urgent health care services. RESULTS: Patient adaptation was correlated with ethnicity and accounted for more variance in all outcomes than did ethnicity. The unique variance accounted for by adaptation was small to moderate, whereas that accounted for by ethnicity was negligible. CONCLUSIONS: It is possible to identify and measure ecocultural domains that better account for variation in important health services outcomes for patients with type 2 diabetes than does ethnicity. Going beyond the study of ethnic differences alone and measuring the correlated factors that play a role in disease management can advance understanding of the phenomena involved in this variation and provide better direction for service design and delivery.