Troglitazone-induced hepatic failure leading to liver transplantation. A case report.

BACKGROUND: Troglitazone is a new drug for the treatment of type 2 diabetes. Although mild liver injury occurred in 1.9% of participants in controlled trials, the U.S. Food and Drug Administration has received reports of five postmarketing cases of severe liver disease that resulted in death or liver transplantation. OBJECTIVE: To report the clinical and histopathologic characteristics of a patient with troglitazone-associated severe liver injury leading to transplantation. DESIGN: Case report. SETTING: Two university hospitals. PATIENT: A 55-year-old woman taking troglitazone, 400 mg/d, and insulin, 120 U/d. INTERVENTION: Discontinuation of troglitazone therapy, pretransplantation liver biopsy, and liver transplantation. RESULTS: Early nonspecific symptoms were attributed to other causes and were not evaluated. After the patient had used troglitazone for 3.5 months, massive loss of liver parenchyma and symptoms of liver failure developed, necessitating liver transplantation. CONCLUSION: Troglitazone may cause subfulminant liver failure.

Frequency and impact of SMBG on glycemic control in patients with NIDDM in an urban teaching hospital clinic.

Few published reports have documented the value of SMBG on glycemic control in patients with non-insulin-dependent diabetes mellitus (NIDDM), and no reports have evaluated predominantly African American patients who are at high risk for NIDDM and associated complications. In this study a 13-item survey was given to 98 patients with NIDDM to assess the frequency of self-monitoring of blood glucose (SMBG) and its impact on glycemic control. Sixty-one patients performed SMBG and 37 did not. More SMBG testers were taking insulin compared with the nontesters. GHb was comparable between groups. Among the testers there was no difference in mean GHb values based on the frequency of SMBG. Most testers performed SMBG before meals (93%) and recorded their values (85%); many had difficulty obtaining a good blood sample (30%). The most common reason for not testing was cost of supplies (77%). Performance of SMBG in these NIDDM patients was not associated with better glycemic control. Cost was a prohibitive factor for the nontesters.

Mexiletine in the symptomatic treatment of diabetic peripheral neuropathy.

OBJECTIVE: To evaluate the efficacy and safety of mexiletine in the symptomatic treatment of diabetic peripheral neuropathy (DPN). METHODS: In this prospective, double-blind study, 29 patients were randomized to receive mexiletine 600 mg/d or matching placebo for 3 weeks. A four-item symptom score (FIS), which rated pain, dysesthesias, paresthesias, and nightly exacerbations of symptoms, and a 100-mm visual analog scale (VAS), which rated pain intensity, were completed by patients before and after treatment. At the end of treatment independent patient and investigator global assessments were made. Patients reported adverse effects after 1 and 3 weeks of treatment. RESULTS: Treatment groups were similar at baseline. The difference between the median changes in FIS scores (mexiletine = 5.5, placebo = 2) was not statistically significant. Overall symptom response was similar in both treatment groups as demonstrated by both global assessments (p = 0.19). The mean change in VAS score from baseline to posttreatment was determined for both groups and the difference between these mean scores was 16.5 mm (95% CI, -7.1 to 40.2 mm) (p = 0.16). Inadequate statistical power (1-beta = 0.40) may have resulted from small sample size, small magnitude of effect, or variability in the measured effect. Adverse effects were more common in the mexiletine group, though not statistically significant. One patient receiving mexiletine was hospitalized for palpitations. CONCLUSIONS: Because of conflicting reports of mexiletine's efficacy in the treatment of symptomatic DPN, this drug should be reserved for patients unresponsive or intolerant to standard therapy, without evidence of heart disease, and with sensations of burning heat, formication, or stabbing pain.

Dyslipidemias in patients with diabetes mellitus: classification and risks and benefits of therapy.

To characterize the lipid and lipoprotein abnormalities in patients with diabetes mellitus and evaluate the risks and benefits of marketed pharmacologic therapies, a MEDLINE search of the National Library of Medicine data base was performed of studies published from January 1966 to March 1994. Clinical trials assessing effects on lipids and lipoproteins, and adverse effects of marketed lipid-lowering agents were extracted. Reviews and other relevant articles were included if they provided information regarding lipid and lipoprotein metabolism or guidelines on the treatment of dyslipidemias in patients with diabetes mellitus. An extensive review of clofibrate was not included. The most common dyslipidemia in patients with poorly controlled insulin-dependent diabetes mellitus (IDDM) is combined elevated triglyceride and cholesterol levels, with reduced high-density lipoprotein (HDL) cholesterol (mixed hyperlipidemia). Hypertriglyceridemia combined with a reduced HDL cholesterol is the most common dyslipidemia in patients with noninsulin-dependent diabetes mellitus, but essentially any pattern of dyslipidemia may be present. Small and dense low-density lipoprotein (LDL), glycosylation of lipoproteins, and increased oxidized lipoproteins may be present in patients with diabetes mellitus; all contribute to accelerated atherosclerotic cardiovascular disease. Insulin therapy generally corrects quantitative lipid abnormalities in patients with IDDM, so drug treatment is seldom indicated. Diet, exercise, and insulin or oral sulfonylureas will improve hypertriglyceridemia and low HDL concentrations, but do not always return them to normal. Drug therapy is indicated when nonpharmacologic measures are inadequate. It is administered based on the effects of each agent on lipids and lipoproteins, patient age, adverse effect profile, patient tolerability, and drug-disease and drug-drug interactions. A fibric acid derivative is the drug of choice for marked hypertriglyceridemia in patients with diabetes mellitus. Niacin can worsen glycemic control, but it may be required in severe hypertriglyceridemia, hypercholesterolemia, or mixed hyperlipidemia. Bile-acid binding resins may accentuate hypertriglyceridemia but may be useful in selected patients with marked hypercholesterolemia and normal triglycerides. Hydroxymethylglutaryl coenzyme A reduced inhibitors are preferred in patients with elevated LDL cholesterol and mild hypertriglyceridemia. Patients with marked lipid abnormalities or mixed hyperlipidemias may require carefully dosed combinations of lipid-lowering drugs.

Family leave policies, job share, and child care at U.S. schools and colleges of pharmacy.

A 10-question survey was mailed to the deans of 74 schools and colleges of pharmacy to characterize family leave policies, child care, and job share opportunities. Data were tabulated as percentage response received, and analyzed by geographic region and by public compared with private institutions. Sixty-four surveys were completed (response rate 86%). Forty-eight (75%) schools reported having a formal written family leave policy: 47 offered maternity leave, 31 parental leave, 27 caregiver leave, 24 paternal leave, and 24 adoptive or foster parent leave. The duration and compensation for family leave varied among schools. A statistical difference was found between the Northeast (100%) and South (55%) in having such a policy. On-site child care was available at 26 (41%) schools, including both infant and child care in 12 and additional sick child care in 2. Three (5%) schools reported faculty job share positions.

Branched-chain amino acid support of stressed patients.

Branched-chain amino acid-enriched formulas have been evaluated in a number of clinical trials. The efficacy of these solutions in the management of stressed patients is controversial. This review discusses the proposed benefits of the branched-chain amino acid-fortified solutions and summarizes prospective clinical trials regarding their use in stressed patients. A cost comparison is also included.