Clinical trial evidence for the cardioprotective effects of omega-3 fatty acids.

The notion that marine omega (w)-3 fatty acids might have beneficial cardiovascular effects was first suggested by epidemiologic studies in Greenland Inuits published in the late 1970s. These simple observations spawned hundreds of other studies, the confluence of which strongly suggests a true cardioprotective effect of w-3 fatty acids. The strongest confirmation has come from the publication of three randomized clinical trials, all of which reported benefits to patients with preexisting coronary artery disease. The most convincing of these was the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico (GISSI)-Prevezione study, in which 5654 patients with coronary artery disease were randomized to either w-3 fatty acids (850 mg/d) or usual care. After 3.5 years, those taking the w-3 fatty acids had experienced a 20% reduction in overall mortality and a 45% decrease in risk for sudden cardiac death. These findings support the view that relatively small intakes of w-3 fatty acids are indeed cardioprotective, and suggest that they may operate by stabilizing the myocardium itself.

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.

Endocrine emergencies. Recognizing clues to classic problems.

Although the possibility of an endocrine emergency occurring in a primary care setting may seem remote, awareness of such emergencies is crucial for appropriate management. While some symptoms are specific to classic endocrine disorders, other symptoms, such as nausea, vomiting, and diarrhea, are so general that the diagnosis may not be considered initially. In these situations, careful and thoughtful diagnostic studies can be lifesaving.

Thyroid dysfunction in the severely ill and elderly. Forget the classic signs and symptoms.

Manifestations of thyrotoxicosis and hypothyroidism are often ill-defined in elderly and seriously ill patients, and signs and symptoms may suggest a nonendocrine disease process instead. It is vitally important that physicians be aware of the possibility of thyroid disease in such patients. Failure to suspect the diagnosis may result in improper treatment and use of invasive diagnostic tests that not only fail to yield helpful results but also are potentially detrimental to the outcome. It is also essential to be able to distinguish between test abnormalities that indicate primary thyroid dysfunction and those that reveal an adaptive response to nonthyroidal illness.

Efficacy and safety of reformulated, micronized glyburide tablets in patients with non-insulin-dependent diabetes mellitus: a multicenter, double-blind, randomized trial.

The subjects were 206 patients (123 men, 83 women) with non-insulin-dependent diabetes mellitus, aged 33 to 80 years. For at least 4 weeks prior to the study each subject had been taking 5-mg tablets of original, nonmicronized glyburide (Micronase tablets) in doses of 5, 10, 15, or 20 mg daily. In a double-blind 12-week study, the subjects were randomly assigned to continue receiving 5-mg tablets of original glyburide or to substitute 3-mg tablets of reformulated, micronized glyburide (Glynase PresTab tablets) for the original tablets. Glyburide tablets had been reformulated to improve their bioavailability. Baseline mean fasting serum glucose levels in the groups taking reformulated and original glyburide were 169.3 and 168.3 mg/dl, respectively; at study end point, their respective serum glucose levels were 186.0 and 177.0 mg/dl. The differences between groups were not significant; in both groups, however, end point glucose levels were significantly higher than baseline levels. Baseline hemoglobin A1C levels in the groups taking reformulated and original glyburide were both 7.6%; at study end point, hemoglobin A1C levels had improved slightly in each group to 7.4% and 7.5%, respectively. The differences between and within groups at end point were not significant. No between-group differences at baseline or at end point were found in mean levels of postprandial serum glucose, fasting C-peptide, or postprandial C-peptide. Medical events experienced by the subjects in the two groups were similar in nature and number. Changes in other laboratory test results, vital signs, and weight were not clinically meaningful.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin-like growth factor-binding protein-3 proteolysis is induced after elective surgery.

The insulin-like growth factors (IGFs) are bound to several binding proteins (IGFBPs) that appear to regulate IGF transport, receptor binding, and action. The concentrations of these peptides are altered by catabolic conditions. To determine if IGF-I and IGFBP levels change after surgery, sera were obtained from 16 patients before and after cholecystectomy. Immunoreactive IGF-I measured in plasma samples from which IGFBPs had been extracted did not change postoperatively. In contrast, IGF-I determined in unextracted samples increased roughly 3-fold postoperatively, presumably due to changes in IGFBPs. Two days postoperatively, IGFBP-3 levels, determined by ligand blot, averaged 36% of preoperative values, whereas levels of IGFBP-2 and a 24,000 mol wt IGFBP did not change significantly. Similarly, by immunoblot, intact IGFBP-3 was decreased 84.2 +/- 20.2%, and a 31,000 mol wt IGFBP-3 fragment increased 57.5 +/- 47.4% postoperatively. Coincubation of postoperative, but not preoperative, sera with control sera resulted in a significant decrease in IGFBP-3 and production of proteolytic fragments. IGFBP-3 proteolytic activity in postoperative sera was markedly inhibited by antipain, Na-p-tosyl-L-lysine chloromethyl ketone, phenylmethylsulfonylfluoride, aprotinin, o-phenanthroline, and EDTA, but not by leupeptin or N-tosyl-L-phenylalanine chloromethyl ketone. This pattern of inhibition is consistent with a metal-dependent trypsin-like serine protease. We speculate that proteolysis of IGFBP-3 may alter tissue uptake of IGF-I and thereby help to counteract the catabolic state caused by surgery.

Thyrotoxicosis in the critically ill.

The thyrotoxic patient offers a considerable challenge to the critical care physician because the "obvious" diagnosis often will be a cardiac (or other nonthyroidal) problem, but the "correct" diagnosis will be an endocrinologic one. The importance of considering the diagnosis of thyrotoxicosis in any patient with tachyarrhythmias, new-onset congestive heart failure, weight loss, or change in mental status cannot be overstated. Treatment for presumed thyroid disease sometimes will have to be initiated prior to the availability of the results of diagnostic tests. Timely and appropriate treatment of the thyroid problem is vital for a successful outcome in treating patients with thyrotoxicosis.

Unilateral adrenal hyperplasia as a cause of primary aldosteronism.

We have described a patient with unilateral adrenal hyperplasia, a rare cause of primary aldosteronism, and reviewed the literature on this subject. The treatment of this disorder appears to be surgical. Whether its pathogenesis is related to the more common varieties of primary aldosteronism is open to speculation.