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Biomedical subjects

F Whitehouse

Publications and source records attributed to F Whitehouse.

14 recordsLinked to original sources

Adjunctive therapy with pramlintide lowers HbA1c without concomitant weight gain and increased risk of severe hypoglycemia in patients with type 1 diabetes approaching glycemic targets.

AIMS: In long-term clinical trials in patients with type 1 diabetes spanning a wide range of HbA1c, addition of pramlintide to existing insulin regimens led to reductions in HbA1c that were accompanied by weight loss and no increase in overall severe hypoglycemia event rates. Given that weight gain and increased hypoglycemia risk contribute to the difficulty of attaining HbA1c targets (<7 %), the question arose whether pramlintide could benefit patients approaching, but not reaching glycemic targets with insulin alone. To address this question, we conducted a pooled analysis from 3 long-term clinical trials, including all patients with an entry HbA1c between 7.0 % and 8.5 %. METHODS: Within the subset of patients with an entry HbA1c between 7.0 % and 8.5 % (approximately 28 % of all patients enrolled in the 3 studies), 196 were treated with placebo + insulin (baseline HbA1c 7.9+/-0.4 %, body weight 76.0+/-14.3 kg [mean+/-SD]) and 281 with pramlintide+insulin (baseline HbA1c 7.9+/-0.4 %, body weight 75.4+/-13.1 kg). Endpoints included placebo-corrected changes from baseline to week 26 in HbA1c, body weight, and the event rate of severe hypoglycemia. RESULTS: Adjunctive therapy with pramlintide resulted in significant reductions in HbA1c and body weight from baseline to week 26 (0.3 % and 1.8 kg, placebo-corrected treatment differences, respectively, both p<or=0.0009). These changes occurred without an increase in the overall risk of severe hypoglycemia (1.40 pramlintide vs. 1.86 placebo, events/patient-year of exposure). CONCLUSIONS: Addition of pramlintide to insulin therapy may help patients with type 1 diabetes who are approaching, but not yet reaching, glycemic targets with insulin alone to achieve further reductions in HbA1c without concomitant weight gain and increased risk of severe hypoglycemia.

Adult↗

A Web-based diabetes care management support system.

BACKGROUND: Because of the often asymptomatic nature of diabetes and the long period between sustained hyperglycemia and observable complications, appropriate diabetes care relies on a long-term program of secondary prevention. Yet routine monitoring and screening among patients with diabetes is less than optimal. To support the provision of routine care to patients with diabetes, the Center for Health Services Research, Henry Ford Health System (Detroit), developed a Web-based Diabetes Care Management Support System (DCMSS). A nonrandomized, longitudinal study was conducted (January 1, 1998-October 31, 1999) with 13,325 health maintenance organization patients with diabetes who were aligned to 190 primary care providers practicing in 31 primary care clinics. RESULTS: Three DCMSS features--clinical practice guidelines, patient registries, and performance reports--were made available via a corporate intranet within an existing electronic medical record. The effect of DCMSS usage frequency was evaluated on the likelihood of a patient's receipt of glycated hemoglobin testing, lipid profile testing, and retinal examinations. Logistic regression models controlling for patient sociodemographic and clinical characteristics, and the testing history of the patient, the primary care physician, and the primary care clinic, were fit using generalized estimating equation methods. The more often a physician used DCMSS, the more likely his or her patients were to receive lipid profile testing (OR [odds ratio] = 1.01, 95% CI [confidence interval] = 1.01-1.02). Compared with patients of physicians who never used the system, patients of physicians who initiated 12 sessions were an estimated 19% more likely (95% CI = 7%-33%) to receive lipid profile testing. The analyses also suggested that the likelihood of a patient receiving a retinal exam was associated with system usage (OR = 1.01, 95% CI = 1.01-1.01). No relationship was found between system use and glycated hemoglobin testing. CONCLUSIONS: Computerized systems of clinical practice guidelines, patient registries, and performance feedback may help improve the rate of routine testing among patients with diabetes.

Adult↗

Troglitazone in combination with sulfonylurea restores glycemic control in patients with type 2 diabetes. The Troglitazone Study Group.

OBJECTIVE: To determine if the combination of troglitazone (a peroxisome proliferator-activated receptor-gamma activator) and sulfonylurea will provide efficacy not attainable by either medication alone. RESEARCH DESIGN AND METHODS: There were 552 patients inadequately controlled on maximum doses of sulfonylurea who participated in a 52-week randomized active-controlled multicenter study. Patients were randomized to micronized glyburide 12 mg q.d. (G12); troglitazone monotherapy 200, 400, or 600 mg q.d. (T200, T400, T600); or combined troglitazone and glyburide q.d. (T200/G12, T400/G12, T600/G12). Efficacy measures included HbA1c, fasting serum glucose (FSG), insulin, and C-peptide. Effects on lipids and safety were also assessed. RESULTS: Patients on T600/G12 had significantly lower mean (+/- SEM) FSG (9.3 +/- 0.4 mmol/l; 167.4 +/- 6.6 mg/dl) compared with control subjects (13.7 +/- 0.4 mmol/l; 246.5 +/- 6.8 mg/dl; P < 0.0001) and significantly lower mean HbA1c (7.79 +/- 0.2 vs. 10.58 +/- 0.18%, P < 0.0001). Significant dose-related decreases were also seen with T200/G12 and T400/G12. Among patients on T600/G12, 60% achieved HbA1c < or =8%, 42% achieved HbA1c < or =7%, and 40% achieved FSG < or =7.8 mmol/l (140 mg/dl). Fasting insulin and C-peptide decreased with all treatments. Overall, triglycerides and free fatty acids decreased, whereas HDL cholesterol increased. LDL cholesterol increased slightly, with no change in apolipoprotein B. Adverse events were similar across treatments. Hypoglycemia occurred in 3% of T600/G 12 patients compared with <1% on G12 or troglitazone monotherapy CONCLUSIONS: Patients with type 2 diabetes inadequately controlled on sulfonylurea can be effectively managed with a combination of troglitazone and sulfonylurea that is safe, well tolerated, and represents a new approach to achieving the glycemic targets recommended by the American Diabetes Association.

Blood Glucose↗

Evaluation of the sterility and stability of insulin from multidose vials used for prolonged periods.

Diabetic patients frequently use their insulin vials for prolonged periods, even though antibacterial preservatives used in multidose insulin vials are not required to be effective beyond 28 days. For this reason, we evaluated the antibacterial activity present in multidose insulin vials for up to 50 days. Multidose lente insulin vials were inoculated with S. aureus and P. aeruginosa. Vials incubated at room temperature (21 degrees C) were sterile by 48 hours, whereas when they were incubated at refrigerator temperatures (4 degrees C), S. aureus contamination persisted up to the 17th day and P. aeruginosa were killed after 10 days. The same vials were serially contaminated on days 17, 30, and 50, and a similar antibacterial effect was maintained. Sixty-nine multidose insulin vials used for an average of 53 days were cultured. Eight vials demonstrated bacterial contamination with 1 cfu/ml of S. epidermidis or Propionibacterium acnes. No endotoxin was detected in the multidose vials used for more than 28 days. Insulin assays on 40 multidose insulin vials used for more than 28 days showed an average insulin content of 101.6 +/- 1.9 units/ml. This study did not demonstrate significant bacterial contamination, endotoxin activity, or insulin degradation of multidose insulin in vials used for periods longer than 28 days. In addition, antibacterial preservatives were more effective at room temperature than at refrigerator temperature; thus, the practice of patients not refrigerating insulin vials is sensible.

Bacteria↗

Selective autocytotoxicity in a model system of Escherichia coli K-12 recombinants.

Autocytotoxicity was shown by Lac(+) recombinant strains of Escherichia coli K-12 when their growth was inhibited in media containing o-nitrophenyl-beta-d-galactopyranoside. Lac(-) strains without lactose permease or beta-galactosidase activity grew well. Selective autocytotoxicity was shown by simultaneous inhibition of Lac(+) cells and multiplication of Lac(-) cells grown together in this medium.

Culture Media↗

Immunologic enhancement of tumor xenografts by pepsin-degraded immunoglobulin.

The serums from guinea pigs previously injected with mouse Ehrlich ascites tumor cells were fractionated to obtain gamma(2)-immunoglobulin. This immunoglobulin was degraded with pepsin to obtain an F(ab')(2) fragment. Fresh tumor cells were incubated with immunoglobulin or the fragment and injected into normal guinea pigs. The growth of these cells as tumor xenografts was inhibited by the gamma(2)-immunoglobulin and enhanced by the F(ab')(2) fragment. Similar incubation of tumor cells with normal guinea pig gamma(2)-globulin or its derived F(ab')(2) fragment did not alter subsequent tumor growth.

Animals↗