Novel antiepileptic drug levetiracetam decreases dyskinesia elicited by L-dopa and ropinirole in the MPTP-lesioned marmoset.

Long-term dopamine replacement therapy of Parkinson's disease leads to the occurrence of dyskinesias. Altered firing patterns of neurons of the internal globus pallidus, involving a pathological synchronization/desynchronization process, may contribute significantly to the genesis of dyskinesia. Levetiracetam, an antiepileptic drug that counteracts neuronal (hyper)synchronization in animal models of epilepsy, was assessed in the MPTP-lesioned marmoset model of Parkinson's disease, after coadministration with (1) levodopa (L-dopa) or (2) ropinirole/L-dopa combination. Oral administration of levetiracetam (13-60 mg/kg) in combination with either L-dopa (12 mg/kg) alone or L-dopa (8 mg/kg)/ropinirole (1.25 mg/kg) treatments was associated with significantly less dyskinesia, in comparison to L-dopa monotherapy during the first hour after administration. Thus, new nondopaminergic treatment strategies targeting normalization of abnormal firing patterns in basal ganglia structures may prove useful as an adjunct to reduce dyskinesia induced by dopamine replacement therapy without affecting its antiparkinsonian action.     

Effects of orchiectomy and polyestradiol phosphate therapy on serum lipoprotein lipids and glucose tolerance in prostatic cancer patients

In 17 prostatic cancer patients, changes in the plasma lipoprotein pattern, including high density lipoprotein (HDL) subfractions, and in glucose tolerance were compared after 6 months on parenteral polyestradiol phosphate (PEP; Estradurin, 80 or 160 mg/month) with the respective changes in orchiectomized patients. In the estrogen group there was no change in the total serum cholesterol level, whereas in the orchiectomy group an increase of 10% was observed. Estrogen therapy resulted in a significant increase of serum HDL (11%) and HDL2 cholesterol (26%) levels; in the orchiectomy group these fractions remained unchanged. Estrogen therapy induced a significant decrease in total serum triglycerides (24%) and in low density lipoprotein triglycerides (27%); in the orchiectomy group reverse changes were observed. PEP treatment caused changes in the serum lipoprotein pattern, which apparently decreases the risk of atherosclerosis.     

Effects of Ethanol on Human Natural Killer Cell Activity: In Vitro and Acute, Low-Dose In Vivo Studies

Chronic use of ethanol may cause a variety of immunological abnormalities in humans. In this study, we have determined the effects of an acute, low dose of ethanol (0.5 g/kg), administered either intravenously or orally, to normal, nonalcoholic male volunteers, on natural killer cell (NK) activity. We have also examined the effects of a 4-hr incubation with ethanol, in concentrations ranging from 0 to 320 mg/dl, on human NK activity in vitro. NK activity was measured by the ⁵¹Cr release assay technique in all of these studies, using peripheral blood mononuclear cells prepared from blood obtained from healthy, nonalcoholic volunteers. Eight subjects received ethanol in vivo; cells from nine subjects were used for the in vitro studies. Blood ethanol concentrations were determined at multiple time points before and after ethanol administration for the in vivo studies; for the in vitro studies, ethanol concentrations were measured from each assay sample both before and after the incubation period. Gas chromatography was used for determinations of both blood alcohol and medium ethanol concentrations. Results of the in vivo studies showed that a single dose of ethanol (0.5 g/kg), administered either intravenously (with resultant peak blood levels transiently up to 89 mg/dl) or orally (with resultant peak blood levels transiently up to 40 mg/dl at the time of the NK assay), did not alter NK activity. However, results of the in vitro studies showed a significant dose-dependent decrease ( p < 0.001) in NK activity when ethanol exposure was sustained for 4 hr at concentrations of 80 mg/ dl and above. We conclude that one of the possible causes for a higher incidence of certain viral infections and malignant tumors among chronic alcoholics may be due, in part, to this observed direct effect of ethanol on NK cytotoxicity.     

A school curriculum-based exercise program increases bone mineral accrual and bone size in prepubertal girls: two-year data from the pediatric osteoporosis prevention (POP) study.

This 2-year prospective controlled exercise intervention trial in 99 girls at Tanner stage 1, evaluating a school curriculum-based training program on a population-based level, showed that the annual gain in BMC, aBMD, and bone size was greater in the intervention group than in the controls. INTRODUCTION: Most exercise intervention studies in children, evaluating the accrual of BMD, include volunteers and use specifically designed osteogenic exercise programs. The aim of this study was to evaluate a 2-year general school-based exercise intervention program in a population-based cohort of girls at Tanner stage 1. MATERIALS AND METHODS: Forty-nine girls 7-9 years of age in grades 1 and 2 in one school were included in a school curriculum-based exercise intervention program of general physical activity for 40 minutes per school day (200 minutes/week). Fifty healthy age-matched girls in three neighboring schools, assigned to the general Swedish school curriculum of physical activity (60 minutes/week), served as controls. All girls were premenarchal, remaining in Tanner stage 1 during the study. BMC (g) and areal BMD (aBMD; g/cm2) were measured with DXA of the total body (TB), the lumbar spine (L2-L4 vertebrae), the third lumbar vertebra (L3), the femoral neck (FN), and the leg. Volumetric BMD (vBMD; g/cm3) and bone size were calculated at L3 and FN. Total lean body mass and total fat mass were estimated from the total body scan. Height and weight were also registered. Baseline measurements were performed before the intervention was initiated. Follow-up was done after 2 years. RESULTS: No differences between the groups were found at baseline in age, anthropometrics, or bone parameters. The annual gain in BMC was greater in the intervention group than in the controls: L2-L4, mean 3.8 percentage points (p = 0.007); L3 vertebra, mean 7.2 percentage points (p < 0.001); legs, mean 3.0 percentage points (p = 0.07). The intervention group had a greater annual gain in aBMD: total body, mean 0.6 percentage points (p = 0.006), L2-L4, mean 1.2 percentage points (p = 0.02), L3 vertebra, mean 1.6 percentage points (p = 0.006); legs, mean 1.2 percentage points (p = 0.007). There was also a greater mean annual gain in bone size in the L3 vertebra (mean 1.8 percentage points; p < 0.001) and in the FN (mean 0.3 percentage points; p = 0.02). CONCLUSIONS: A general school-based exercise program for 2 years for 7- to 9-year-old girls (baseline) enhances the accrual of BMC and BMD and increases bone size.     

Increased suicide risk among Danish women with non-melanoma skin cancer, 1971-1999.

More suicides than expected (standardized mortality ratio=1.3; 95% confidence interval=1.1-1.6) compared to the population risk were found among Danish women with a diagnosis of non-melanoma skin cancer in the period 1971-1999 but not among men. The increased risk might be associated with a different personality type in this cancer group.     

The developing mouse thyroid: embryonic vessel contacts and parenchymal growth pattern during specification, budding, migration, and lobulation.

Normal mouse thyroid development has been revised to identify critical morphogenetic events. The early thyroid primordium associates with the aortic sac endothelium at the time of specification and budding. The vascular contact is lost after the thyroid buds from the pharyngeal endoderm, but is resumed before the gland divides to form two lobes. Lateral expansion of parenchyma takes place along the course of the third pharyngeal arch arteries. Thyroid precursor cells expressing Titf1/Nkx2.1 do not proliferate until the migration stage, implicating that progenitors likely are recruited from outside the thyroid placode. Early lobulation involves engulfment of the entire ultimobranchial bodies by the growing midline thyroid. At the same time, proliferation of the ultimobranchial body epithelium is silenced preceding the differentiation of C cells. Before folliculogenesis, thyroid lobe enlargement is reminiscent of a budding-branching-like growth pattern. It is suggested that thyroid inductive signals arise from embryonic vessels, and that this provides ideas to conceptually new pathogenetic mechanisms of thyroid dysgenesis.     

The hospital cost of vertebral fractures in the EU: estimates using national datasets

The purpose of this study was to estimate the hospital cost of vertebral fractures in the EU using national datasets to explore some of the methodologic limitations associated with such an approach. Hospital costs for vertebral fractures across the EU were compared with the hospital costs associated with hip fractures. Additionally, these costs were placed into the health care context by making comparisons with national health care expenditure. All EU Ministries of Health were contacted to identify national datasets to estimate the average length of stay, cost per diem and the number of patients discharged with vertebral fractures. Where national information was not available expert opinion and data from the relevant literature were used instead. Countries show a marked difference in the length of stay between men and women, with differences ranging from 0.32 days in Austria to 20.2 days in Spain. The average hospitalization rate was found to be 8% across the EU, with higher rates found for men than for women. Interestingly a positive correlation between health expenditure per capita and hospitalization rates was found. The total cost of vertebral fractures in the EU was estimated at euro 377 million per year. Across the EU the hospital cost of a vertebral fracture was on average 63% that of a hip fracture. National datasets allow us to estimate the cost of vertebral fractures in the EU but show limitations. In the absence of large scale prospective studies, national datasets need to be further refined to ensure more accurate estimations of the cost of vertebral fractures in the EU.     

Arteriosclerotic changes in the myocardium, lung, and kidney in dogs with chronic congestive heart failure and myxomatous mitral valve disease.

BACKGROUND: The occurrence of small vessel arteriosclerosis in the myocardium, kidney, and lung in dogs with naturally occurring myxomatous mitral valve disease has not been previously investigated systematically. METHODS: Twenty-one dogs with naturally occurring congestive heart failure and 21 age-matched, sex-matched, and weight-matched control dogs underwent extensive pathological and histopathological examination. Morphometry and scoring of tissue sections were used to measure arterial narrowing and fibrosis in the myocardium, kidney, and lung; and intimal thickness and plaque formation in the aorta and pulmonary artery. RESULTS: Dogs with congestive heart failure had significantly more arterial narrowing in the left ventricle (P < .003), lung (P < .0001), and kidney (P < .02); intimal-medial thickening in the pulmonary artery (P = .04); and fibrosis in the left ventricle (P < .0001) than control dogs. However, they did not have more plaque formation or intimal-medial thickening in the aorta than controls. There was significantly more arterial narrowing in papillary muscles than in all other locations in dogs with congestive heart failure (P < .002). In control dogs, arterial changes were less pronounced and did not differ in different locations. CONCLUSIONS: Dogs with naturally occurring myxomatous mitral valve disease have significantly more arterial changes in the myocardium, lung, and kidney, and significantly more fibrosis in the myocardium than control dogs. This could have important implications in the management of myxomatous mitral valve disease and raises interesting questions about the occurrence and importance of intramural small vessel disease in humans with primary mitral valve prolapse.     

Do patient characteristics,disease, or treatment explain social inequality in survival from colorectal cancer?

This paper investigates the association between individually measured socioeconomic status (SES) and all-cause survival in colorectal cancer patients, and explores whether factors related to the patient, the disease, or the surgical treatment mediate the observed social gradient.