Variants in intron 13 of the ELMO1 gene are associated with diabetic nephropathy in African Americans.

Variants in the engulfment and cell motility 1 (ELMO1) gene are associated with nephropathy due to type 2 diabetes mellitus (T2DM) in a Japanese cohort. We comprehensively evaluated this gene in African American (AA) T2DM patients with end-stage renal disease (ESRD). Three hundred and nine HapMap tagging SNPs and 9 reportedly associated SNPs were genotyped in 577 AA T2DM-ESRD patients and 596 AA non-diabetic controls, plus 43 non-diabetic European American controls and 45 Yoruba Nigerian samples for admixture adjustment. Replication analyses were conducted in 558 AA with T2DM-ESRD and 564 controls without diabetes. Extension analyses included 328 AA with T2DM lacking nephropathy and 326 with non-diabetic ESRD. The original and replication analyses confirmed association with four SNPs in intron 13 (permutation p-values for combined analyses = 0.001-0.003), one in intron 1 (P = 0.004) and one in intron 5 (P = 0.002) with T2DM-associated ESRD. In a subsequent combined analysis of all 1,135 T2DM-ESRD cases and 1,160 controls, an additional 7 intron 13 SNPs produced evidence of association (P = 3.5 x 10(-5)- P = 0.05). No associations were seen with these SNPs in those with T2DM lacking nephropathy or with ESRD due to non-diabetic causes. Variants in intron 13 of the ELMO1 gene appear to confer risk for diabetic nephropathy in AA.

Prevalence of osteoporosis risk factors and treatment among women aged 50 years and older.

We conducted a cross-sectional, retrospective review to evaluate screening, diagnosis, and treatment of 389 women aged 50 years or older at risk for osteoporosis in a large primary care practice. Records randomly selected from a computerized database were reviewed for drug history, age, height, weight, and osteoporosis-related diagnoses, symptoms, and risk factors. Among the 389 women, 255 (65.5%) were receiving bone-preserving treatment (247 estrogen replacement exclusively). Most (70.4%) were white, with an average age of 61 years, and an average of 3.3 risk factors for osteoporosis. Risk factors were postmenopausal status 94%, age 65 years or older 53%, hysterectomy 39%, cigarette smoking 33%, and physical inactivity 30%. By logistic regression, the only positive predictor of antiresorptive therapy was hysterectomy (adjusted odds ratio [AOR] 2.52, 95% confidence interval [CI] 1.54-4.14). Negative predictors were physical inactivity (AOR 0.44, 95% CI 0.25-0.71), rheumatoid arthritis (AOR 0.31, 95% CI 0.12-0.79), and age 65 years and older (AOR 0.54, 95% CI 0.34-0.86). Controlling for age, women with four or more risk factors were 62% less likely to be receiving antiresorptive treatment (AOR 0.38, 95% CI 0.23-0.64) than those with fewer risk factors.

Critical pathways: the time is here for pharmacist involvement. American College of Clinical Pharmacy.

Successful development, implementation, and assessment of the effectiveness of critical pathways involves many processes and tools. Numerous pathways have been developed and the value of this tool in improving patient care has been demonstrated in some patient groups.27,29 Pharmacists are becoming more involved, but the window of opportunity is small. Critical pathways are routinely being utilized to optimally sequence time-appropriate interventions of the interdisciplinary plan of care set forth to achieve patient satisfaction and desired outcomes. Pharmacists must seize the chance to provide pharmaceutical care and assure their participation in the development and implementation of critical pathways.

Effects of Terazosin on Glycemic Control, Cholesterol, and Microalbuminuria in Patients with Non--Insulin-Dependent Diabetes Mellitus and Hypertension.

The use of antihypertensive agents that have positive or neutral effects on blood sugar, lipid profiles, and microalbuminuria can be important clinical treatment for patients with diabetes. We evaluated the effects of both terazosin, a selective alpha-one-adrenergic blocker, and hydrochlorothiazide (HCTZ), a standard mild antihypertensive agent, on glycemic control, urinary albumin excretion rate overnight total cholesterol, and other parameters in non--insulin-dependent diabetes mellitus (NIDDM) patients. A randomized, placebo-controlled, cross-over design was implemented in 25 patients. Over an 8-week treatment period fasting plasma glucose (FPG) and glycosylated hemoglobin (GHgb) improved in the terazosin group. Post-treatment FPG was 200 plus minus 85 and 187 plus minus 71 for patients who received HCTZ and terazosin, respectively. Although the GHgb improved significantly for terazosin patients (12.2 plus minus 5.8 for HCTZ versus 10.7 plus minus 4.6 for terazosin, p = 0.03), microalbuminuria did not improve in terazosin patients in this pilot study. A larger randomized study with tighter blood pressure end points are needed to assess fully the impact of terazosin on micoroalbuminuria and overall glycemic control in the NIDDM patient.

Measurement feasability of advanced glycated end-products from skin samples after antioxidant vitamin supplementation in patients with type 2 diabetes.

PURPOSE: To determine the feasibility of measuring advanced glycated end-products (AGEs)from skin samples and to evaluate the effects of a combination of vitamins E and C on measures of glycemic control and AGEs in patients with type 2 diabetes mellitus. METHODS: Twenty-two patients with type 2 diabetes from a Family Medicine clinic were randomly assigned to receive a daily dietary supplement containing either a combination of 400 mg of vitamin E and 500 mg of vitamin C or matching placebo for a period of one year. AGEs were measured from skin samples taken from the buttock. RESULTS: Nineteen subjects completed this one-year pilot study. There were no major problems found in measuring AGEs from skin samples taken from the butttock. Neither the treatment or placebo group had significant changes in glycemic control, protein glycosylation or AGEs. DISCUSSION: Skin samples taken from the buttock area may be an appropriate site for the determination of AGE levels as this procedure appeared to be well-tolerated. Daily vitamin E and C supplementation did not improve measures of glycemic control or AGE levels in this small sample of patients with type 2 diabetes. Because antioxidant vitamins are inexpensive and free of side effects, additional research using a variety of antioxidant vitamin combinations and dosing regimens is needed.

Uses and safety of acyclovir in pregnancy.

Acyclovir, an antiviral nucleoside analogue, is a widely used agent highly specific for herpes simplex and varicella-zoster viruses. Unintended exposure to acyclovir early in pregnancy, which is not uncommon, may cause excessive maternal and physician anxiety. This drug has not been studied prospectively in large numbers of pregnant women and lacks the Food and Drug Administration's approval for gestational use unless benefits clearly outweigh potential fetal harm. However, data published since acyclovir became available do not indicate increased adverse effects related to its use in pregnancy, especially if prescribed in selected situations, such as disseminated primary herpes simplex infections or maternal varicella pneumonia. This article reports the impact of inadvertent acyclovir exposure on a woman during the first trimester of pregnancy and reviews the literature on acyclovir's pharmacology, safety profile, and potential uses during pregnancy.

Troglitazone or metformin in combination with sulfonylureas for patients with type 2 diabetes?

BACKGROUND: Combination oral therapy is often used to control the hyperglycemia of patients with type 2 diabetes. We compared the effectiveness of metformin and troglitazone when added to sulfonylurea therapy for patients with type 2 diabetes who had suboptimal blood glucose control. METHODS: We used a randomized 2-group design to compare the efficacy, safety, and tolerability of troglitazone and metformin for patients with type 2 diabetes mellitus that was inadequately controlled with diet and oral sulfonylureas. Thirty-two subjects were randomized to receive either troglitazone or metformin for 14 weeks, including a 2-week drug-titration period. The primary outcome variable was mean change in the level of glycosylated hemoglobin (Hb A1c) from baseline. Secondary outcomes included mean changes from baseline in fasting plasma glucose and C-peptide levels, renal or metabolic side effects, and symptomatic tolerability. RESULTS: The addition of either troglitazone or metformin to oral sulfonylurea therapy significantly decreased Hb A1c levels. Both treatment regimens also significantly reduced fasting plasma glucose and C-peptide levels. We found no significant differences between the treatment arms in efficacy, metabolic side effects, or tolerability. CONCLUSIONS: Our results demonstrate that troglitazone and metformin each significantly improved Hb A1c, fasting plasma glucose, and C-peptide levels when added to oral sulfonylurea therapy for patients with type 2 diabetes who had inadequate glucose control.

Angiotensin-II receptor antagonists: their place in therapy.

Angiotensin-II receptor antagonists (or blockers) are a newer class of antihypertensive agents. These drugs are selective for angiotensin II (type 1 receptor); unlike angiotensin-converting enzyme inhibitors, they do not inhibit bradykinin metabolism or enhance prostaglandin synthesis. Angiotensin-II receptor antagonists are well tolerated. Cough occurs much less often with these agents than with angiotensin-converting enzyme inhibitors, and they do not adversely affect lipid profiles or cause rebound hypertension after discontinuation. Clinical trials indicate that angiotensin-II receptor antagonists are effective and safe in the treatment of hypertension. Their use in congestive heart failure and renal disease is under investigation.

Significant drug-nutrient interactions.

Many nutrients substantially interfere with pharmacotherapeutic goals. The presence of certain nutrients in the gastrointestinal tract affects the bioavailability and disposition of many oral medications. Drug-nutrient interactions can also have positive effects that result in increased drug absorption or reduced gastrointestinal irritation. Knowing the significant drug-nutrient interactions can help the clinician identify the nutrients to avoid with certain medications, as well as the therapeutic agents that should be administered with food. This information can be used to educate patients and optimize pharmacotherapy.

Important features of blood glucose meters.

OBJECTIVE: To provide an overview of several blood glucose meters that will enhance practicing pharmacists' knowledge and understanding of these devices to allow education of the patient with diabetes. DATA SOURCES: Original and review articles, blood glucose meter package inserts and manuals. DATA SYNTHESIS: Careful blood glucose control is essential to prevent long-term complications of diabetes. Newer blood glucose meters have a broad variety of features, including small size, extended memory capacity, blood glucose manipulation techniques, and computer downloading capabilities. The decision to choose a blood glucose meter should be based on a number of criteria, including the patient's needs, ease of use, and affordability. CONCLUSION: Pharmacists must position themselves to differentiate among the numerous blood glucose meters available on the market and make appropriate recommendations based on patient-specific needs.

Alendronate: a bisphosphonate for treatment of osteoporosis.

The bisphosphonates have been investigated over the past two decades for the treatment of various diseases of bone and calcium metabolism that are characterized by increased bone resorption, including osteoporosis, Paget's disease, primary hyperparathyroidism, hypercalcemia of malignancy and metastatic bone disease. The bisphosphonate alendronate was recently approved by the U.S. Food and Drug Administration as a therapy for postmenopausal osteoporosis. This agent is currently the bisphosphonate of choice for clinical use. In postmenopausal osteoporosis, alendronate has been shown to increase bone mineral density and to decrease the rate of new fractures. Adverse effects are not usually a problem when 10 mg per day of alendronate is given with at least 6 oz of water 30 minutes before ingestion of the first food or beverage of the day.

Performance of three blood glucose meters.

OBJECTIVE: To evaluate the performance of three blood glucose meters. METHODS: The One Touch II (LifeScan, Milpitas, CA), Glucometer Elite (Bayer, Elkhart, IN), and Accu-Chek Advantage (Boehringer Mannheim, Indianapolis, IN) were compared with a reference laboratory method (Technicon Chem System, Tarrytown, NY). Blood glucose meters used in this study were validated by a clinically oriented approach known as the error grid analysis (EGA), for which the performance of the meters was compared to a laboratory standard, and by the criteria of the American Diabetes Association (ADA). Limits of agreement were evaluated using differences from the reference laboratory method and 95% Cls. Capillary blood was obtained from study participants in fasting state with the morning blood draw and tested on the three meters simultaneously. RESULTS: A total of 120 blood glucose meter readings were analyzed; values ranged from 62 to 396 mg/dL. For all three meters, at least 75% of the capillary blood glucose values fell into zone A (acceptable) of the EGA. The number of values falling into zone B (unacceptable) were 10, 8, and 6 for the Accu-Chek Advantage, the One Touch II, and the Glucometer Elite, respectively. Only 15-25% of the meter glucose readings met the ADA criteria of being within 5% of the laboratory standard. The mean difference from the reference values was least with the Glucometer Elite. CONCLUSIONS: The majority of blood glucose determinations obtained on the meters used in this study were within the acceptable limits using the EGA. The Glucometer Elite meter had the fewest values in the unacceptable range and had the least mean difference from reference laboratory values.

Approaches to the treatment of hyperlipidemia in the solid organ transplant recipient.

OBJECTIVE: To review the literature investigating increased lipid concentrations in transplant recipients and the use of lipid-lowering agents in this population. DATA SOURCES: Relevant articles were identified from a MEDLINE search using the terms transplantation, hyperlipidemia, immunosuppression, and therapy including diet, gemfibrozil, bile acid sequestrants, nicotinic acid, probucol, and hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors. Selected literature, including controlled studies, was used in this review. STUDY SELECTION: Articles published since 1970 pertaining to hyperlipidemia in solid organ transplant recipients. Emphasis was placed on clinical trials that investigated approaches to the treatment of hyperlipidemia in transplant recipients. DATA EXTRACTION: Original articles and reviews were obtained to select material pertinent to the objectives. DATA SYNTHESIS: Descriptions of lipid concentrations in the transplant patient and treatment approaches used, including potential complications, were reviewed. CONCLUSIONS: Hyperlipidemia is an important risk factor for coronary heart disease in the solid organ transplant patient. Treatment alternatives include diet modification and, in most cases, pharmacologic intervention that should be based on the type of hyperlipidemia. The HMG-CoA reductase inhibitors are effective agents in the treatment of hyperlipidemia in the transplant recipient and generally are used as single therapy in low dosages to minimize the risk of myositis or rhabdomyolysis.

Safe discontinuation of antihypertensive therapy.

We summarize herein the clinical and pathophysiological features of antihypertensive withdrawal syndrome and its risk factors, management, and prevention. Antihypertensive withdrawal syndrome occurs most frequently with beta-blocking agents and centrally acting antihypertensives such as clonidine hydrochloride. This syndrome resembles a state of sympathetic nervous system hyperactivity. In the most critical case, it can be severe and life threatening. Antihypertensive dosages, particularly for beta-blockers and clonidine, should be tapered slowly rather than discontinued abruptly.

Salivary theophylline monitoring: reassessment and clinical considerations.

To assess the reliability of salivary theophylline concentrations for patient monitoring, concentrations of theophylline in sera and saliva of 50 patients (ages 6-81 years) receiving oral or parenteral theophylline were determined by two methods: a rapid dry-phase apoenzyme reactivation system (ARIS) and fluorescence polarization immunoassay (FPIA). Saliva production was stimulated by both citric acid (CA) and parafilm (PF). With both analytical methods, there were excellent correlations between salivary theophylline concentration, CS, and unbound serum theophylline concentration CU (r2 > 0.95), and between CS and total serum theophylline concentration, CT (r2 > 0.85). CA- and PF-stimulated CS by FPIA resulted in concentrations within 2.0 micrograms/ml of the actual CU for 100% of the samples measured (n = 47). By ARIS, 100% of the PF-stimulated CS and 93.6% of the CA-stimulated CS determinations were within 2.0 micrograms/ml of the CU (n = 47). To evaluate the predictive capabilities of PF- and CA-stimulated saliva, one-half (n = 24) of the patients were randomly selected and their data used to predict the CT for the remaining patients. FPIA PF-CS predicted 83.3% (20/24) of CT within +/- 2 micrograms/ml, while ARIS CA-CS predicted 75.0% within +/- 2 micrograms/ml. There was no difference between FPIA CS and ARIS CS results by multivariate analysis of variance (MANOVA), but there was a difference between PF-CS and CA-CS (p < 0.05). However, when CU was used as a covariant, there was no significant difference. Using appropriate saliva collection procedures and the FPIA system, we conclude that CS provides adequate reliability for therapeutic drug monitoring of theophylline.