Human epithelial growth factor receptor 2[Ile655Val] polymorphism and risk of breast fibroadenoma.

Studies on the association between the Ile to Val polymorphism at codon 655 of the human epithelial growth factor receptor 2 (HER-2) gene and susceptibility to breast cancer have been reported for almost all ethnic populations, with both positive or negative conclusions. No study, however, has yet been focused on the possible association between this gene and its predisposition to benign breast lesions, especially on risk for fibroadenoma. We aimed to study the association of the single nucleotide polymorphism V655 HER-2 gene polymorphism with histologically verified breast fibroadenoma risk. We conducted a molecular epidemiological case-control study of 70 breast fibroadenoma cases without cellular atypia and 172 healthy female controls. We found that the Val variant allele and genotype frequency of this polymorphism is higher in cases with fibroadenoma; however, this difference was not significant (allele Val 655: 27.86 and 22.67% in fibroadenoma and controls, respectively; genotype Ile/Val: 35.71 and 38.37% and Val/Val: 10.0 and 3.49% in fibroadenoma and controls, respectively). Applying logistic regression analysis, we found an increased risk of fibroadenoma formation in carriers of the Val allele (odds ratio = 1.17; 95% confidence interval = 0.67-2.05), in which the highest risk was associated with homozygous genotype (odds ratio = 3.07; 95% confidence interval = 0.97-9.72), but this risk was not significant. Stratification by age (cut-off 45 years) revealed the highest risk of fibroadenoma among young women homozygous for the Val allele (odds ratio = 3.30). The risk, however, was slightly increased (odds ratio = 1.24) among older carriers of the aberrant allele in their genotype as well, but it was not significant. In spite of insignificant differences, our results indicate that HER-2 Ile655Val polymorphism, especially in a homozygous form might play some role in the etiology of breast fibroadenoma formation. The significance of this susceptibility, however, will have to be verified by larger studies.     

Progressive slippage after pinning for slipped capital femoral epiphysis

The authors retrospectively reviewed seven cases of progressive slipped capital femoral epiphysis after screw fixation. All seven patients initially presented with chronic symptoms, and five had an acute exacerbation of symptoms with the appearance of an acute-on-chronic slip. Of the other two, one had obvious motion at the proximal femoral physis and the other had increased symptoms but did not have an obvious acute slip radiographically. All underwent percutaneous screw fixation. In four patients a single screw was placed, and in three patients two screws were placed. No patient became symptom-free after surgery. Slip progression was noted on average 5 months after treatment. Radiographs in all patients revealed an increase in slip severity and loss of screw purchase in the femoral neck while fixation in the proximal femoral epiphysis remained secure. One patient had hypothyroidism and another Cushing disease, both diagnosed after the slipped epiphysis. Slips occurring in children with underlying endocrinopathies, and unstable slips in children with a history of antecedent knee or hip pain (commonly called an acute-on-chronic slip) may be susceptible to screw fixation failure. In such patients, close radiographic follow-up, particularly in the presence of continued symptoms, is required to document slip progression and fixation failure as soon as possible.     

Evaluation of the Tg.AC transgenic mouse assay for testing the human carcinogenic potential of pharmaceuticals--practical pointers, mechanistic clues, and new questions

Transgenic mouse strains with genetic alterations known to play a role in the multistage process of carcinogenesis are being used increasingly as models for evaluating the human carcinogenic potential of chemicals and pharmaceuticals. The Tg.AC transgenic mouse is one of the strains currently being used in such alternative short-term carcinogenicity testing protocols. This review is focused on recent data from studies designed to evaluate this model's ability to discriminate carcinogens from noncarcinogens. Details relating to protocol design that can significantly impact study outcome are described. Data relating to mechanisms of chemical tumor induction in the Tg.AC model are reviewed, and questions have been formulated to encourage research to further guide appropriate future applications of this model.     

Determination of eight trichothecene mycotoxins using GCMSMS methods. I. elaboration of MS/MS conditions

Trichothecene mycotoxins are commonly distributed in cereals in the world. Rapid and accurate methods for the determination of these toxins are required to prevent the intoxication of human and to contribute to the supply of safe foods and feed. MSMS mode was applied for identification of eight trichothecene mycotoxins with Finnigan/Mat GCQ GC/MS system. We describe here optimal parameters of CID and to obtain best pairs of ions (precursor ions and daughter ions) for all analysed toxins.     

Oxidative stress and neutrophil activation--the two keystones of ischemia/reperfusion injury

The widespread introduction of fibrinolytics and recently also PTCA in the treatment of myocardial infarction has changed the picture of modern cardiology. But this therapy also raises new problems and challenges. One of them is the occurrence of extensive tissue injury caused by reperfusion. Reinstitution of oxygen to the ischemic tissues initiates various processes leading to generation of reactive oxygen species (ROSs). Acting on the plasma membrane ROS damage its organization and release various proinflammatory agents. Different proteins, including receptors, ionic channels, transporters or components of transduction pathways are substrates of oxidation by ROSs. Their changed structure results in altered functioning and disruption of vital cellular processes. Another key factor of reperfusion injury is activation and infiltration of infarcted area by polymorphonuclear leukocytes (PMNs). Multiple studies identified consecutive stages of PMN activation and substances being involved in it. Main interest lies in cellular adhesion molecules, particularly selectins and beta2 integrins, as their antagonists were repeatedly found to diminish neutrophil activation and infarct size. Nevertheless new publications strike at the foundations of the established order and confront the relation between neutrophil infiltration and infarct size. PMNs are linked by close ties to other cells involved in inflammatory response. Seemingly also in cardiac ischemia-reperfusion injury, the activity of neutrophils is modulated by lymphocytes and macrophages. The article describes mutual interactions between different factors involved in the reperfusion injury that may enable preparing new treatments, hopefully as effective and successful as reperfusion therapy.     

Myelodysplastic syndrome at a large tertiary care community hospital: analysis according to the international prognostic scoring system

The outcome of patients diagnosed myelodysplastic syndromes (MDS) between 1990 and 1997 from William Beaumont Hospital (WBH) was analyzed according to the International Prognostic Scoring System (IPSS) risk categorization. A retrospective study of 195 MDS patients wa s performed. Seventy-nine patients with MDS, in whom a karyotype was obtained and with an adequate follow-up were included in the final analysis. Cases of proliferative CMML (WBC > 12x10(9)/l) were excluded from the study. The overall median survival was 3.1 years, and median survival stratified by IPSS was 3.4, 4.1 and 0.5 years for the INT-1, INT-2 and high risk group and not yet reached for the low risk group. The overall survival by IPSS subcategorization were 6.88, 5.29, 5.30 and 2.12 years for the low, INT-1, INT-2, and high risk groups respectively. Cytogenetics were significant in predicting the overall survival. The IPSS score stratified patients into risk categories for development of AML. The risk of development into AML was 8, 8, 33 and 54% for the low, INT-1, INT-2 and high risk groups, respectively. We conclude that IPSS score can be useful in predicting survival and AML evolution in some MDS patients.