Risk factors for dislypidemia in obese children and adolescents

OBJECTIVE: To assess the risk of dislypidemia associated with obesity in children and adolescents. MATERIAL AND METHODS: A cross sectional study was conducted with 62 obese children (BMI > 95 centile and tricipital skinfold thickness > 90 centile) and 70 non-obese children (BMI 5-85 centile) ages 5-15 years, without chronic diseases. Subjects' characteristics and family background of chronic diseases were collected and a lipid profile was determined. The risk of lipid alterations in the obese children was calculated using odds ratio (OR) and multivariate analysis. RESULTS: Mean age was 9.8 +/- 2.7 years in both groups; 63 girls and 69 boys were included. Obesity was associated with abnormal values for cholesterol, triglycerides, LDL, HDL and dislypidemia (> 1 abnormal value) (OR 4.47-15.0). In obese children and adolescents the multivariate analysis showed that female gender was associated with dislypidemia. CONCLUSION: Obesity in children and adolescents is associated with high risk of dislypidemia; the risk is higher among females.     

In vitro induction of immune responses to shared tumor-associated antigens in rhabdomyosarcoma

Purpose

Currently, novel therapies to improve survival of patients with rhabdomyosarcoma (RMS) are being investigated. One of the new approaches involves immunotherapy using tumor-specific T-lymphocytes. An effective prolonged immune-mediated response against tumor cells is dependent upon the response of helper T-lymphocytes (HTLs) to tumor-associated antigens in the presence of histocompatibility lymphocyte antigen surface proteins.

Methods

Rhabdomyosarcoma tumor lysate-pulsed human dendritic cells were used to stimulate HTL precursors (naive CD4+ T-cells) in vitro. After 3 rounds of antigen stimulation with antigen-presenting cells, the T-cells were tested for reactivity (T-cell proliferation assays) against a large panel of tumor lysate-pulsed autologous antigen-presenting cells.

Results

Using peripheral blood mononuclear cells from normal naive donors, we have been able to generate HTL clones that recognize and proliferate to multiple tumor cell lines. The HTLs were induced using lysate from a single alveolar RMS tumor cell line (RMS13). The clones generated recognized all of the alveolar RMS cell lines (RMS13, Rh18, Rh28, Rh30, and Rh41), prostate cancer cell lines (LNCAP and LAPC4), melanoma cell lines (Mel 624 and G361), and breast cancer cell line (SKBR3). Helper T-lymphocytes recognition was also confirmed by interferon-γ production. The clones did not recognize colon, lymphoma, ovarian carcinoma, ERMS or Epstein-Barr virus (EBV) transformed B-cells. This recognition was histocompatibility lymphocyte antigen class II restricted and was not an allogeneic response.

Conclusion

The results of this work demonstrate that HTLs, exposed to RMS lysate, are able to recognize and respond to a broad range of tumor types suggesting that a common antigen exist among these different tumors. These findings suggest novel treatment strategies for patients with RMS using tumor lysate to induce antitumor immune responses.     

Chromosomal deletion unmasking a recessive disease: 22q13 deletion syndrome and metachromatic leukodystrophy

A deletion on one chromosome and a mutant allele on the other may cause an autosomal recessive disease. We report on two patients with mental retardation, dysmorphic features and low catalytic activity of arylsulfatase A. One patient had a pathogenic mutation in the arylsulfatase A gene ( ARSA ) and succumbed to metachromatic leukodystrophy (MLD). The other patient had a pseudoallele, which does not lead to MLD. The presenting clinical features and low arylsulfatase A activity were explained, in each patients, by a deletion of 22q13 and, thereby, of one allele of ARSA .     

A population-based case-control study of Selective Serotonin Reuptake Inhibitors (SSRIs) and breast cancer: The impact of duration of use, cumulative dose and latency

Background  

Selective serotonin reuptake inhibitors (SSRIs), a popular class of antidepressants, may increase breast cancer risk by stimulating the secretion of prolactin, a potential tumour promoter. We evaluated the effects of duration of SSRI use, cumulative dose, and latency on the risk of breast cancer by conducting a population-based case-control study utilizing Saskatchewan health databases.     

Effects of immediate versus delayed antihypertensive therapy on outcome in the Systolic Hypertension in Europe Trial

BACKGROUND: To assess the impact of immediate versus delayed antihypertensive treatment on the outcome of older patients with isolated systolic hypertension, we extended the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial by an open-label follow-up study lasting 4 years. METHODS: The Syst-Eur trial included 4695 randomized patients with minimum age of 60 years and an untreated blood pressure of 160-219 mmHg systolic and below 95 mmHg diastolic. The double-blind trial ended after a median follow-up of 2.0 years (range 1-97 months). Of 4409 patients still alive, 3517 received open-label treatment consisting of nitrendipine (10-40 mg daily) with the possible addition of enalapril (5-20 mg daily), hydrochlorothiazide (12.5-25 mg daily), or both add-on drugs. Non-participants (n = 892) were also followed up. RESULTS: Median follow-up increased to 6.1 years. Systolic pressure decreased to below 150 mmHg (target level) in 2628 participants (75.0%). During the 4-year open-label follow-up, stroke and cardiovascular complications occurred at similar frequencies in patients formerly randomized to placebo and those continuing active treatment. These rates were similar to those previously observed in the active-treatment group during the double-blind trial. Considering the total follow-up of 4695 randomized patients, immediate compared with delayed antihypertensive treatment reduced the occurrence of stroke and cardiovascular complications by 28% (P = 0.01) and 15% (P = 0.03), respectively, with a similar tendency for total mortality (13%, P = 0.09). In 492 diabetic patients, the corresponding estimates of long-term benefit (P < 0.02) were 60, 51 and 38%, respectively. CONCLUSIONS: Antihypertensive treatment can achieve blood pressure control in most older patients with isolated systolic hypertension. Immediate compared with delayed treatment prevented 17 strokes or 25 major cardiovascular events per 1000 patients followed up for 6 years. These findings underscore the necessity of early treatment of isolated systolic hypertension.     

Compromised first permanent molars: an orthodontic perspective

The first permanent molar (FPM) is commonly subject to significant compromise which may arise due to caries or endodontic complication, or from developmental anomalies such as hypoplasia. Compromised teeth with questionable prognosis may result in short and long-term clinical dilemmas. This review article highlights the factors that require careful consideration when a compromised FPM is detected and the importance of timely FPM extraction. Several clinical cases are described in detail to discuss possible treatment options from the orthodontic perspective.     

Murine Hertwig's anemia: premature death after normal bone marrow transplantation is radiation dose-dependent

Marrow transplantation therapy in mice with heritable blood disorders usually leads to rapid blood cell normalization, but is sometimes followed by pancytopenia and premature death. This is especially true in mice with Hertwig's anemia (an/an). Unlike the +/+ recipients, 100% of whom survive for over a year, 66% of the mutant mice die by 6 months posttransplantation, and the rest die soon thereafter. It is not clear whether premature death is due to the radiation dose (10 Gy) or to the fact that the F1 mutant mice receive parental-type cells known to induce hybrid resistance. In the present report, experiments were designed to determine whether the F1-an/an host is more sensitive to radiation and/or resistant to continued expansion of the parental-type +/+ cells. The mutant mice are, indeed, more sensitive to irradiation, with an LD100/30 of 7 Gy as compared with an LD100/30 of 10 Gy for the +/+ mice. The times of anemia onset and death for mutant mice implanted with +/+ cells postirradiation is also radiation dose-dependent. Further evidence that death is due to host radiation damage rather than F1 hybrid resistance was provided by transplanting cells from three morbid 10 Gy-irradiation recipients into unirradiated, anemic, stem cell-deficient, F1-W/Wv secondary hosts. All recipients were repopulated by the original parental cells, were cured of their anemia, and survived for 52 weeks posttransplantation. The an/an mouse's heightened susceptibility to radiation damage appears to be the major factor in early death after transplantation therapy.