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Biomedical subjects

L R Reynolds

Publications and source records attributed to L R Reynolds.

13 recordsLinked to original sources

Rosiglitazone amplifies the benefits of lifestyle intervention measures in long-standing type 2 diabetes mellitus.

AIMS: To evaluate the efficacy of a lifestyle intervention programme including meal replacements and increased physical activity upon body weight, diabetes control and other cardiovascular risk factors in obese, poorly controlled, insulin-treated, type-2-diabetic individuals and to assess the impact of concomitant rosiglitazone (RSG) therapy. METHODS: This 6-month intervention study included 21 patients with type 2 diabetes mellitus (DM) requiring insulin therapy with haemoglobin A1c (HbA1c) > 7% and with a body mass index (b.m.i.) > 27. All subjects were enrolled in a 6-month lifestyle intervention programme and randomized to placebo or RSG 4 mg/day. Participation in the lifestyle programme included meal replacements, increased intake of fruits and vegetables and increased daily physical activity. Measured end-points included body weight, waist circumference, blood pressure, HbA1c and serum lipids, before entry into the study. RESULTS: The baseline mean b.m.i. was 36.4 and the mean HbA1c was 9.0%. The greatest weight losses occurred during the first 12 weeks (19 lbs for RSG, 13.4 lbs for placebo) with a greater weight loss at each point for the group receiving RSG. Waist circumference declined by 2.8 and 4.0 inches for the placebo and RSG groups. Systolic BP declined 16.2 mmHg in the placebo group and 14.3 mmHg in the RSG group. Diastolic blood pressure decreased by 12.8 mmHg in the placebo group. HbA1c was reduced significantly by 1.3% for the placebo group and 1.1% in the RSG group. DISCUSSION: This study demonstrates the benefits of lifestyle intervention using meal replacements and increased physical activity with resultant modest weight loss in long-standing, poorly controlled type 2 diabetes. RSG did not impede weight loss and, in fact, amplified some of the positive benefits of lifestyle intervention.

Biomarkers↗

Reemergence of insulin pump therapy in the 1990s.

The publication of the landmark Diabetes Control and Complications Trial results in 1993 provided a strong impetus to achieve near-normalization of blood glucose levels in type I diabetic patients using intensive insulin therapy programs. Recent studies show less hypoglycemia with this form of intensive therapy and equivalent or improved glycemic control. Insulin pump therapy is achieving wider acceptance and application in diabetes management. This commentary reviews the current status of insulin pump therapy, including indications and future directions.

Child↗

Hypervolemic-hemodilution during cerebral ischemia in rats: effect of diaspirin cross-linked hemoglobin (DCLHb) on neurologic outcome and infarct volume.

In a rat model of middle cerebral artery occlusion (MCAo) and reperfusion (120 min), previous studies have demonstrated that hemodilution with molecular hemoglobin decreases ischemic brain injury. However, long-term recovery data on the therapeutic efficacy of molecular hemoglobin for cerebral ischemia are lacking. Accordingly, we assessed the effect of hemodilution, with alpha-alpha diaspirin cross-linked hemoglobin (DCLHb, 10 g/dl) on neurologic outcome and infarct volume after 120 min of MCAo and 72 h of reperfusion. Ischemia was achieved by passing a 0.26-mm suture, via the external carotid artery, to internally occlude the middle cerebral artery. Immediately after MCAo, the rats were randomized to one of the following groups: Control-hematocrit not manipulated (44%); 30/Hct-hematocrit maintained at 30% with DCLHb; or 16/Hct-hematocrit maintained at 16% with DCLHb. After 120 min of MCAo, the suture was removed and the rats allowed to recover. Daily neurologic examinations were performed, and after 72 h, the brains were analyzed for infarct volume with TTC stain. Infarct volume (mm3) was less in the 30/Hct group (67 +/- 10; mean +/- SD) than in the Control group (141 +/- 17); and less in the 16/Hct group (40 +/- 12) than the other two groups (p < 0.05). Neurologic outcome was improved in both hemodilution groups versus the Control group (p < 0.05). These data are consistent with previous studies, performed in a model of short-term reperfusion, which indicate a dose-dependent decrease in ischemic injury by DCLHb.

Animals↗

Treatment of type I diabetes with a combination of glyburide and insulin.

OBJECTIVE: To assess the ability of a combination of insulin and an oral hypoglycemic agent (glyburide) to improve the overall glycemic control in a population of patients with type I diabetes. DESIGN: Randomized, placebo-controlled, double-blind trial. SETTING: Community-based, university-affiliated, family medicine group. PATIENTS: Men and women between 18 and 68 years of age with type I diabetes. INTERVENTIONS: Subjects were observed and titrated on an insulin-only regimen for 12 weeks (phase I). Subjects were then randomized to receive either placebo or glyburide 10 mg/d for an additional 12 weeks (phase II). MAIN OUTCOME MEASURES: Glucose measurements were taken at breakfast, lunch, supper, and bedtime. Each patient also was followed sequentially for serum lipids, glycosylated hemoglobin, (Hb A1c) and daily insulin utilization. RESULTS: Average fasting blood glucose (FBG) measurements were significantly lower in the glyburide-treated group during phase II (9.22 +/- 0.55 mmol/L) compared with baseline (10.27 +/- 0.93 mmol/L) and phase I (10.41 +/- 0.55 mmol/L). A decrease in the average Hb A1c concentration in the glyburide group was evident by week 4 and was sustained for the duration of the study. The average daily insulin dose rose significantly in the glyburide but not the placebo group compared with baseline. Total cholesterol, triglycerides, and low-density lipoprotein cholesterol did not change significantly in either group over the course of the study. High-density lipoprotein cholesterol increased significantly over baseline in the glyburide group during phase II. Several patients experienced dramatic improvements in glycemic parameters after the addition of glyburide to their insulin regimens. CONCLUSIONS: Improvements were observed in the FBG and Hb A1c measurements of this heterogeneous population of patients with type I diabetes after the addition of glyburide to their insulin regimens. The study failed to find consistent trends in glycemic control when evaluating mean changes in FBG measurements.

Adolescent↗

Long-term follow-up of diabetic patients using insulin infusion pumps. Considerations for future clinical application.

Current debate about the use of insulin infusion pumps in the treatment of diabetes mellitus is partly attributable to a lack of available data about the long-term course of patients who use pumps. We evaluated the course of our first 20 patients treated with insulin infusion pumps. Two or more years after the inception of therapy, only half of these patients were still using the insulin infusion pump. Psychosocial stresses, which affected glycemic control, were identified retrospectively in a majority of patients, but were not appreciated when pump therapy was initiated, despite our best attempts to do so. Mean hemoglobin A1 levels decreased significantly for the entire group and for the subgroup that did not discontinue pump therapy. These results suggest that insulin pump programs must have the resources to provide appropriate support for all candidates, including unsuitable candidates, who present for treatment with insulin infusion pumps.

Adult↗

Conjunctival biopsy in unexplained hypercalcemia.

A 31-year-old woman presented with hypercalcemia, anemia, azotemia, and splenomegaly. Extensive laboratory studies failed to establish the diagnosis, though sarcoidosis seemed likely on the basis of marked hypercalciuria and restrictive lung disease. Conjunctival biopsy showed noncaseating epithelioid granulomas, confirming the clinical diagnosis. Conjunctival biopsy deserves consideration in the evaluation of the patient with unexplained hypercalcemia or other findings suggestive of saroidosis.

Adult↗

Virilizing adrenocortical carcinoma: role of computed tomography.

A 31-year-old woman who presented with virilization was found to have elevated plasma testosterone and increased urinary 17-KS levels. The apparent source of androgens was detected and defined by CT scanning as a right-sided adrenal mass lesion, which was successfully resected and which proved to be an adrenocortical carcinoma.

Adrenal Cortex Neoplasms↗

Evaluation of the hypercalcemic patient.

Malignancy is the most common cause of hypercalcemia, which may result from direct involvement of bone or from local or distant production of substances that enhance bone resorption. The recognized incidence of primary hyperparathyroidism has increased greatly since the advent of automated biochemical screening. A single parathyroid adenoma is most frequently the cause. Sarcoidosis commonly results in hypercalciuria but seldom causes sustained hypercalcemia. Increased production of 1,25-dihydroxycholecalciferol leads to hyperabsorption of calcium and enhanced bone resorption.

Addison Disease↗

Nephrotic syndrome associated with methimazole therapy.

Thionamide drugs are widely used in the management of hyperthyroidism and are infrequently associated with adverse reactions. We report the development of the nephrotic syndrome during methimazole (Tapazole) therapy in a young man with Graves' disease. His proteinuria remitted promptly with discontinuance of the drug, and renal histologic features bore a striking resemblance to the toxic nephrosis induced in animals by the aminonucleoside of puromycin. In view of the histologic similarities, we propose that methimazole acted as a direct glomerular toxin, inducing the nephrotic syndrome in this patient.

Adult↗

Antithyroid drugs and radioactive iodine. Fifteen years' experience with Graves' disease.

The population for this study included 186 patients who were treated between 1962 and 1977 for diffuse toxic goiter. Patients were divided into two groups according to the primary mode of therapy, which was either thioamides or sodium iodide I 131. Of 96 patients who were treated with primary drug therapy, only 16% experienced a prolonged remission (more than two years) of hyperthyroidism. Except for a greater likelihood of remission among patients with mild hyperthyroidism, no other clinical features of Graves' disease were predictive of the long-term response to drug therapy. Among the 90 patients who received primary sodium iodide I 131 therapy, those who were pretreated with thioamides required a higher total dose to achieve a cure (13.8 mCi vs 9.6 mCi) and had a lower initial incidence of hypothyroidism (54% vs 73%).

Adolescent↗