Chromosomal imbalances in clear cell ependymomas.

Clear cell ependymoma is a rare and diagnostically challenging subtype of ependymoma, whose genetic features are essentially unknown. We studied 13 clear cell ependymomas (five cases WHO grade II, eight cases WHO grade III) by comparative genomic hybridization (CGH). Chromosomal imbalances were found in 12/13 cases. The most common aberrations overall were +1q (38%), -9 (77%), -3 (31%), and -22q (23%). Clear cell ependymomas of WHO grade II were characterized by -9 (40%), whereas WHO grade III cases mainly showed +1q (63%), and +13q (25%), as well as -9 (100%), -3 (38%), and -22q (25%). In contrast to other ependymal tumors, clear cell ependymomas of WHO grade II showed fewer imbalances than WHO grade III samples (1.4 vs 3.5 per case). Although some of the implicated chromosomes have previously been shown to be involved in other ependymoma variants, the striking frequency of +1q, -9, and -3 suggests that aberrations differ between clear cell and other types of ependymomas, in particular, for loss of chromosome 9 which can be regarded as the molecular hallmark of clear cell ependymomas.     

Liver pathology associated with the use of anabolic-androgenic steroids

Abstract: This review examines the liver-damaging side effects of anabolic-androgenic steroids (AAS). It seems that AAS can cause development of peliosis hepatis, subcellular changes of hepatocytes, hepatocellular hyperplasia and hepatocellular adenomas. On the other hand, it has not been convincingly proved that AAS can cause development of hepatocellular carcinomas when used in the usual therapeutic doses. Tumours reported as hepatocellular carcinomas caused by AAS seem to be hyperplastic lesions of a benign nature able to regress with withdrawal of the putative agent. The effects of untraditional combinations and high-dose AAS are not yet known, leaving the possibility of a carcinogenic effect in those cases.     

Serial tomographic imaging with technetium-99m-sestamibi for the assessment of infarct-related arterial patency following reperfusion therapy.

The purpose of this study was to determine the relationship of changes in the severity and extent of hypoperfusion on serial tomographic 99mTc-sestamibi images with patency of the infarct related artery during acute myocardial infarction. We studied 109 patients with acute myocardial infarction using tomographic 99mTc-sestamibi imaging acutely and at 18-48 hr later. Perfusion defect extent and defect area, an index of defect severity, were measured on both studies. Both defect extent and defect area were significantly (p = 0.0001) greater for anterior infarctions than for inferior and lateral infarctions. By two factor analysis of variance, the change in defect area varied significantly with both infarct location (p = 0.0001) and patency of the infarct-related artery (p = 0.002). The change in defect extent also varied significantly with both infarct location (p = 0.0001) and with patency of the infarct-related artery (p = 0.004). In patients with inferior myocardial infarction, a change in defect extent or defect area of greater than 4% or 0.017, respectively, had a positive predictive accuracy of 96% and 93%, respectively, for the identification of a patent infarct artery. Therefore, sequential changes on tomographic 99mTc-sestamibi images are of potential value for the noninvasive assessment of patency of the infarct-related artery.     

Nifedipine aggravates cyclosporine A-induced gingival hyperplasia

Gingival hyperplasia is a common side-effect of immunosuppression with cyclosporine A. Nifedipine is often used to control hypertension in kidney graft recipients. Analysis of gingival status in 106 children transplanted at our centre, and treated either with azathioprine, cyclosporine A or both, revealed significantly higher degrees of gingival overgrowth in those children receiving a combination of cyclosporine A and nifedipine compared with those children treated with cyclosporine A or nifedipine alone. Seven children undergoing gingivectomy at our centre over the past few years had received this combination. After a change in the antihypertensive regimen, avoiding long-term nifedipine medication, and improved dental care with chlorhexidine gel, we noted a reduction in the degree of gingival hyperplasia. In the majority of patients, nifedipine could be replaced by a single drug, usually hydralazine. We therefore recommend avoiding calcium channel blockers in the long-term management of hypertension in patients receiving cyclosporine.     

Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial.

Specific receptors for vitamin D have been identified in human muscle tissue. Cross-sectional studies show that elderly persons with higher vitamin D serum levels have increased muscle strength and a lower number of falls. We hypothesized that vitamin D and calcium supplementation would improve musculoskeletal function and decrease falls. In a double-blind randomized controlled trial, we studied 122 elderly women (mean age, 85.3 years; range, 63-99 years) in long-stay geriatric care. Participants received 1200 mg calcium plus 800 IU cholecalciferol (Cal+D-group; n = 62) or 1200 mg calcium (Cal-group; n = 60) per day over a 12-week treatment period. The number of falls per person (0, 1, 2-5, 6-7, >7 falls) was compared between the treatment groups. In an intention to treat analysis, a Poisson regression model was used to compare falls after controlling for age, number of falls in a 6-week pretreatment period, and baseline 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum concentrations. Among fallers in the treatment period, crude excessive fall rate (treatment - pretreatment falls) was compared between treatment groups. Change in musculoskeletal function (summed score of knee flexor and extensor strength, grip strength, and the timed up&go test) was measured as a secondary outcome. Among subjects in the Cal+D-group, there were significant increases in median serum 25-hydroxyvitamin D (+71%) and 1,25-dihydroxyvitamin D (+8%). Before treatment, mean observed number of falls per person per week was 0.059 in the Cal+D-group and 0.056 in the Cal-group. In the 12-week treatment period, mean number of falls per person per week was 0.034 in the Cal+D-group and 0.076 in the Cal-group. After adjustment, Cal+D-treatment accounted for a 49% reduction of falls (95% CI, 14-71%; p < 0.01) based on the fall categories stated above. Among fallers of the treatment period, the crude average number of excessive falls was significantly higher in the Cal-group (p = 0.045). Musculoskeletal function improved significantly in the Cal+D-group (p = 0.0094). A single intervention with vitamin D plus calcium over a 3-month period reduced the risk of falling by 49% compared with calcium alone. Over this short-term intervention, recurrent fallers seem to benefit most by the treatment. The impact of vitamin D on falls might be explained by the observed improvement in musculoskeletal function.     

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.     

Anti-tumor immunotherapy via antigen delivery from a live attenuated genetically engineered Pseudomonas aeruginosa type III secretion system-based vector.

Immunotherapy requiring an efficient T lymphocyte response is initiated by antigen delivery to antigen-presenting cells. Several studies have assessed the efficiency of various antigen loading procedures, including microbial vectors. Here a live strain of Pseudomonas aeruginosa was engineered to translocate a recombinant antigenic protein into mammalian cells via the type III secretion system, a bacterial device translocating effector proteins into host cells. Optimization of the vector included virulence attenuation and determination of the N-terminal sequence allowing translocation of fused antigens into cells. In vitro delivery of an ovalbumin fragment by the bacterial vector into dendritic cells induced the activation of ovalbumin-specific CD8(+) T lymphocytes. Mice injected with the ovalbumin-delivering vector developed ovalbumin-specific CD8(+) T lymphocytes and were resistant to a subsequent challenge with an ovalbumin-expressing melanoma. Moreover, in a curative assay, injection of the vaccine vector 5 and 12 days after tumor implantation led to a complete cure in five of six animals. These results highlight the utility of type III secretion system-based vectors for anti-tumor immunotherapy.