Association of microsatellite polymorphisms of the human 14q13.2 region with type 2 diabetes mellitus in Latvian and Finnish populations.

A polymorphic microsatellite in intron 6 of the human proteasome core particle PSMA6 gene (HSMS006), and four other microsatellites localized upstream on human chromosome 14q13.2 (HSMS801, HSMS702, HSMS701, HSMS602), were genotyped in 104 type 2 diabetic patients and 129 age-matched control subjects from Latvia and replicated in 91 type 2 diabetic patients and 88 age-matched healthy control subjects from the Botnia Study in Finland. In type 2 diabetic patients from both populations the HSMS006 (TG)22 allele was two times more frequent compared to the control group. In the Latvian population the (CAA)8 allele of the HSMS602 marker was less frequent in the diabetic group, as was the (AC)24 allele of microsatellite HSMS801. Allele frequencies of the HSMS701 and 702 repeats were similar in healthy controls and type 2 diabetic patients. In conclusion, our data suggest that variants in the PSMA6 gene on chromosome 14q13.2 are associated with type 2 diabetes.

Alternative high-performance liquid chromatographic assay for p-aminohippuric acid (PAH): effect of aging on PAH excretion in the isolated perfused rat kidney.

Para-aminohippuric acid (PAH), an indicator of renal plasma flow, is a commonly used marker of organic anion transport by the kidney. An analytical method for PAH using HPLC was developed. The method is simple, fast and requires a minimum amount of organic solvent. Sample preparation involved protein precipitation with zinc sulfate. Para-amino benzoic acid was utilized as an internal standard (IS). Chromatography was performed using a reversed-phase phenyl column with UV detection at a wavelength of 254 nm. Mobile phase consisted of 0.1 M acetic acid and acetonitrile (99:1) at a flow rate of 1 ml/min. The assay was validated over a standard concentration range from 1 to 25 microg/ml. Accuracy, precision, reproducibility and specificity of the method was established with coefficients of variation <10%. The method was sensitive and showed linear response in peak height ratio (analyte:IS) over the concentration range studied (r(2)>0.99). The assay was used to study the effect of aging on PAH excretion in the isolated perfused rat kidney model. Experiments were conducted in kidneys from young (2-3 months, n=6), adult (6-9 months, n=5) and aged (12-16 months, n=3) male Sprague-Dawley rats at an initial drug concentration of 20 microg/ml. Significant differences in kidney function (e.g. glomerular filtration rate and glucose reabsorption) were observed in aged kidneys. Despite a 5-fold reduction in glomerular filtration rate, PAH renal clearance (kidney weight-corrected) decreased by only 2-fold in aged (2.2+/-0.42 ml/min per gram) compared to young (4.6+/-0.70 ml/min per gram, P<0.05) rats. Furthermore, renal excretion ratio was significantly higher in aged rats (27+/-8.0 vs. 15+/-5.0, P<0.05). These preliminary findings challenge the 'Whole Nephron Hypothesis' that assumes parallel reductions in renal filtration and secretory capacity secondary to disease or aging.

Patient-reported adherence to guidelines of the Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

OBJECTIVES: To compare antihypertensive drug compliance with treatment guidelines established by the Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI), and to identify patient adherence to antihypertensive drugs and factors affecting prescribing patterns. METHODS: Patients filling antihypertensive drug prescriptions in metropolitan New York area pharmacies were enrolled. Pharmacy externs collected patient-reported demographics, medical and drug histories, and blood pressure measurements. Compliance with JNC VI guidelines was assessed. RESULTS: Eight hundred twenty-one patients from 102 pharmacies participated. Blood pressure was controlled in 61% of patients at the time of the study. The most prescribed class of antihypertensive agents was angiotensin-converting enzyme inhibitors, followed by diuretics and beta-blockers. Over the study period, compliance with JNC VI guidelines decreased significantly from 85% to 64% (p<0.05). Thirty-seven percent of patients reported consistent adherence to their antihypertensive regimens. Patients' education level was the only factor found to correlate positively with the appropriateness of antihypertensive agents prescribed. CONCLUSION: Compliance with JNC VI guidelines decreased over time, and patient adherence to drug therapy was suboptimal. Continuing-education efforts to reinforce optimal blood pressure management are necessary.

Oxcarbazepine, an antiepileptic agent.

BACKGROUND: Epilepsy is a common neurologic condition. Many of the currently approved pharmacologic agents for its treatment are associated with numerous adverse drug reactions and drug interactions. OBJECTIVE: This review describes the pharmacology and therapeutic use of oxcarbazepine, an analogue of the well-known antiepileptic agent carbamazepine. METHODS: Articles for review were identified through a search of MEDLINE, International Pharmaceutical Abstracts, and EMBASE for the years 1980 through 2000. The terms used individually and in combination were oxcarbazepine, carbamazepine, epilepsy, and seizures. RESULTS: Oxcarbazepine and its primary metabolite have been effective in animal models of epilepsy that generally predict efficacy in generalized tonic-clonic seizures and partial seizures in humans. The exact mechanism of action of oxcarbazepine is unknown, although as with carbamazepine, it is believed to involve blockade of voltage-gated sodium channels. The pharmacokinetic profile of oxcarbazepine is less complicated than that of carbamazepine, with less metabolism by the cytochrome P450 system, no production of an epoxide metabolite, and lower plasma protein binding. The clinical efficacy and tolerability of oxcarbazepine have been demonstrated in trials in adults, children, and the elderly. In a double-blind, randomized, crossover trial in adults, oxcarbazepine 300 mg was associated with a decrease in the mean frequency of tonic seizures (21.4 vs 30.5 seizures during steady-state periods) and tonic-clonic seizures (8.2 vs 10.4) compared with carbamazepine 200 mg (P = 0.05). A multinational, multicenter, double-blind, placebo-controlled, randomized, 28-week trial assessed the efficacy and tolerability of oxcarbazepine at doses of 600, 1200, and 2400 mg as adjunctive therapy in patients with uncontrolled partial seizures. All 3 oxcarbazepine groups demonstrated a reduction in seizure frequency per 28-day period compared with placebo (600 mg, 26% reduction; 1200 mg, 40% reduction; 2400 mg, 50% reduction; placebo, 7.6% reduction; all, P < 0.001). A trial in children assessed the efficacy and toxicity of oxcarbazepine (median dose, 31.4 mg/kg/d) as adjunctive therapy for partial seizures. Patients receiving oxcarbazepine experienced a 35% reduction in seizure frequency, compared with a 9% reduction in the placebo group (P < 0.001). The most common adverse effects associated with oxcarbazepine are related to the central nervous system (eg, dizziness, headache, diplopia, and ataxia) and the gastrointestinal system (eg, nausea and vomiting). Compared with carbamazepine, there is an increased risk of hyponatremia with oxcarbazepine. The frequency and severity of drug interactions are less with oxcarbazepine than with carbamazepine or other antiepileptic agents. CONCLUSIONS: Oxcarbazepine may be considered an appropriate alternative to carbamazepine for the treatment of partial seizures in patients who are unable to tolerate carbamazepine. Its use in nonseizure disorders remains to be examined in large-scale clinical trials, and pharmacoeconomic comparisons of oxcarbazepine with other antiepileptic agents, particularly carbamazepine, are needed.

Urinary lactose: changes postpartum and relation with breast milk production.

Measurement of milk intake by breast-fed infants is difficult and a simple measure would be helpful for research and clinical practice. Maternal urinary lactose excretion has been proposed as a simple measure of lactation performance. The objectives of this study were to describe the pattern of urinary lactose excretion postpartum, and to determine whether lactose excretion could predict breast milk output. Lactose excretion was determined in 50 lactating and 49 nonlactating women at 0.5, 3, and 6 mo postpartum, and in 29 weaning women and 30 nonlactating women at 5, 8, and 11 mo postpartum. Lactose excretion was 4- to 17-fold higher in lactating than in nonlactating women, depending on the time point studied, and was highest in both groups 0.5 mo postpartum. Lactose excretion decreased after weaning but remained higher than in nonlactating women 1.3 mo after weaning was completed. Sixty-two additional women between 1.5 and 12 mo postpartum were studied to determine the ability of urinary lactose to predict milk output. There was a positive association between milk output and urinary lactose excretion, with correlation coefficients ranging from 0.17 to 0.30 depending on the measurement interval for lactose excretion. Lactose excretion could explain 2-9% of the variance in milk output, and could correctly classify 29-40% of individuals into tertiles of milk output. Although urinary lactose excretion reflects changes in biological activity of the mammary gland and gross changes in milk production, it is not a precise predictor of milk output.