German populations with infrequent CHEK2*1100delC and minor associations with early-onset and familial breast cancer

CHEK2*1100delC is associated with a twofold increased breast cancer risk. This was shown in a collaborative analysis of European populations, but not in other populations from Europe and the US. Accordingly, there is a need to clarify the role of CHEK2*1100delC in breast cancer.We established its prevalence in two German populations GENICA (Northrhine-Westphalia, n = 724) and KORA (Bavaria, n = 600) and in women with breast cancer. The latter included cases (n = 688) from the GENICA breast cancer case-control study, patients with early-onset breast cancer (n = 86) and patients with familial breast cancer (n = 71). The latter patient groups were previously investigated for BRCA1/2-mutations and tested negative. Mutation analysis was performed by combined PCR/DHPLC methodology.CHEK2*1100delC was found in 0.9% of GENICA controls and was absent in the KORA controls indicating a significant difference between the two populations (P = 0.03). The frequency of CHEK2*1100delC in age-matched cases of the GENICA collection was 0.8% and thus not different from controls (OR 0.88, 95% CI 0.21–3.50). In patients with early-onset disease CHEK2*1100delC was found at a frequency of 2.3% referring to an increased breast cancer risk of 2.56 (95% CI 0.25–14.58). In patients with familial disease the frequency was 1.4% referring to an increased risk of 1.53 (95% CI 0.03–12.93).Our data showed variations in CHEK2*1100delC prevalence within German populations suggesting possible inaccuracies in breast cancer risk assessments from non population-based studies. In patients with a high-risk profile however, CHEK2*1100delC was indicative for this risk and highest for early-onset breast cancer.     

Birth cohort effect on lung cancer incidence in Taiwanese women 1981-1998

Lung cancer has been the main cause of cancer-related mortality in Taiwanese women since 1986. Gradual increases in both awareness of risks and use of extractor fans in kitchens should reduce the incidence of this disease. To investigate the birth cohort effect on lung cancer incidence in Taiwanese women for 1981-1998, an age-period-cohort (APC) model analysis was employed to study the effects of age, time periods, birth cohorts and histological types of lung cancer. A significant increase in lung cancer incidence among women was found for the period 1981-1998 (r=0.96, P<0.05), principally of adenocarcinoma, then squamous cell carcinoma. Age is the strongest predictor according to the APC model. The birth cohort of 1917-1926 has the highest risk of lung cancer. However, in recent cohorts, particularly those born after 1956, the incidence has fallen. The declining incidence in younger cohorts may be due to the increased use of extractor fans in kitchens reducing exposure to carcinogenic fumes from cooking oil.     

Determination of apoptosis through Bax expression in cryptorchid testis: an experimental study

The aim was to determine the expression of Bax in germ cells of rats with unilateral experimental cryptorchidism, and to evaluate the role of apoptosis in germ cell loss. Twenty-one prepubertal rats were randomly subdivided into three groups after the execution of the left cryptorchidism model. Group 1 (n=8), group 2 (n=6) and group 3 (n=7) rats were killed at the end of the first, second and third month, respectively. Bax expression was assessed in Sertoli cells, spermatogonia and spermatocytes by immunohistochemistry. Percentages of Bax expression in spermatocytes and spermatogonia were decreased in the left testicles in the 2^nd and 3^rd months compared to results obtained in the 1^st month (p<0.05). Percentage of Bax expression in the left testicles of group 1, at the level of both spermatogonia and spermatocytes was higher than that in the right one (p<0.05). However, in groups 2 and 3, the higher Bax expression on the left side was only seen in the spermatocytes (p<0.05). In all groups, the mean weight of the left testicle was lower than that of the scrotal counterpart where the difference was significant only in groups 1 and 3 (p<0.05). The weight of the left and right testicles was increasing with time. In this model of cryptorchidism, the affected testis had a decreased weight compared to the normal one. Based on the increased Bax expression, we think that apoptosis may play a role in the germ cell loss.     

Antifungal activities of propolis collected by different races of honeybees against yeasts isolated from patients with superficial mycoses

Yeasts isolated from patients with superficial mycoses were tested against propolis samples collected from different regions and honeybee races. The minimum inhibitory concentration (MIC) values obtained using the agar dilution methods were compared to the diameters of growth inhibition zones by using the disk diffusion method. The results showed that Candida albicans, C. glabrata, Trichosporon spp., and Rhodotorula sp. were susceptible to low concentrations of propolis, the latter showing a higher susceptibility. Relative to the other propolis tested, the propolis sample collected by Apis mellifera caucasica possessed the highest antifungal activity against all of the superficial mycoses. In contrast, the propolis samples collected by A.m. carnica and A.m. anatolica were the least active samples. Also, the propolis sample from the Adana region is more active than samples from other regions. An increase of MIC values was accompanied by a decrease of growth inhibition zone diameters.     

Inhibitory effects of a fermented ginseng extract, BST204, on the expression of inducible nitric oxide synthase and nitric oxide production in lipopolysaccharide-activated murine macrophages

In this study, the effects of BST204, a fermented ginseng extract, on the expression of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production are looked into. Crude ginseng extract was incubated with ginsenoside-beta-glucosidase to prepare BST204. BST204, unlike lipopolysaccharide (LPS) and crude ginseng extract, did not affect the level of iNOS protein and NO production in unstimulated RAW 264.7 cells. However, it suppressed the level of iNOS protein and NO production in LPS-stimulated RAW 264.7 cells but did not manifest the same effect on the iNOS mRNA level. An investigation of the activating phosphorylation of p70 S6 kinase and 4E-BP1, which are important for translation, was conducted to investigate the suppressive mechanism of iNOS protein. LPS increased the phosphorylation of p70 S6 kinase, but not 4E-BP1, in a time-dependent manner, and BST204 inhibited it in a dose-dependent manner. The expression of iNOS protein, however, was partially suppressed by rapamycin, an upstream inhibitor of p70 S6 kinase. Therefore, this paper suggests that the suppression of iNOS protein by BST204 was partially correlated with the inhibition of p70 S6 kinase activation.     

Endothelin-1 acts via protein kinase C to block KATP channels in rabbit coronary and pulmonary arterial smooth muscle cells

We investigated the effects of the vasoconstrictor endothelin-1 (ET-1) on the whole-cell ATP-sensitive K+ (KATP) currents of smooth muscle cells that were isolated enzymatically from rabbit coronary artery (CASMCs) and pulmonary artery (PASMCs). The size of the KATP current did not differ significantly between CASMCs and PASMCs. ET-1 reduced the KATP current in a concentration-dependent manner, and this inhibition was greater in PASMCs than in CASMCs (half-inhibition values of 12.20 nM and 1.98 nM in CASMCs and PASMCs, respectively). However, the level of inhibition induced by other vasoconstrictors (angiotensin II, norepinephrine, and serotonin) were not significantly different between CASMCs and PASMCs. Pretreatment with the protein kinase C (PKC) inhibitors staurosporine (100 nM) and GF 109203X (1 microM) prevented ET-1-induced inhibition of the KATP current in both arterial smooth muscle cell preparations. The PKC activators phorbol-12,13-dibutyrate (PDBu) and 1-olelyl-2-acetyl-sn-glycerol (OAG) reduced the KATP current in dose-dependent manner. Although the numbers of ET receptors were not significantly different between the 2 arterial smooth muscle cell preparations, the effects of PDBu and OAG were greater on PASMCs. ET-1-induced inhibition of the KATP current was unaffected by the PKA inhibitor Rp-cAMPs (100 microM) and PKA inhibitory peptide (5 microM).     

Serum CA19-9 response as a surrogate for clinical outcome in patients receiving fixed-dose rate gemcitabine for advanced pancreatic cancer

The use of serial serum measurements of the carbohydrate antigen 19-9 (CA19-9) to guide treatment decisions and serve as a surrogate end point in clinical trial design requires further validation. We investigated whether CA19-9 decline represents an accurate surrogate for survival and time to treatment failure (TTF) in a cohort of 76 patients with advanced pancreatic cancer receiving fixed-dose rate gemcitabine in three separate studies. Statistically significant correlations between percentage CA19-9 decline and both overall survival and TTF were found, with median survival ranging from 12.0 months for patients with the greatest degree of biomarker decline (> 75%) compared with 4.3 months in those whose CA19-9 did not decline during therapy (P < 0.001). Using specific thresholds, patients with > or = 25% decline in CA19-9 during treatment had significantly better outcomes than those who did not (median survival and TTF of 9.6 and 4.6 months vs 4.4 and 1.5 months; P < 0.001). Similar results were seen using both 50 and 75% as cutoff points. We conclude that serial CA19-9 measurements correlate well with clinical outcomes in this patient population, and that decline in this biomarker should be entertained for possible use as a surrogate end point in clinical trials for the selection of new treatments in this disease.     

Treatment of children's and adolescent's knee injuries

INTRODUCTION: Authors made 162 knee arthroscopic operations due to hemarthrosis of the knee, acute knee blocking or acute developed instability on patients under 18 years after knee injury during a 12 years period. The retrospective analysis of patient reports shows, that in 61.7% of the cases they found chondral- or osteochondral fracture in the knee. MATERIAL AND METHODS: On three dimensional routine X-ray pictures they were performed after the injury, in 85% of the cases fractures were not seen. Fortunately the most part of the hyalin surface injuries was smaller than 0.5 cm or were situated on less weight-bearing area only hemarthrosis evacuation and removing of loose body were done. If the osteochondral fractures was bigger than 0.5 cm or was broken from the weight-bearing surface, they were fixed by KFI or Herbert-screws. When refixation of osteochondral fracture was not possible technically or in cases of chondral fractures, primary mosaic chondroplasty was used. The correct diagnosis and the early reconstruction of injured hyalin surface in childhood and teenagers is essential regarding to the function of the knee.     

Cardiopulmonary bypass in patients with pre-existing coagulopathy

Patients with pre-existing coagulopathies who undergo surgical interventions are at increased risk for bleeding complications. This risk is especially true in cardiac surgical procedures with cardiopulmonary bypass (CPB) because of the necessity for heparinization and the use of the extracorporeal circuits, which have destructive effects on most of the blood components. In this review, cases of cardiac surgeries in patients with certain pre-existing coagulopathies are summarized, which could shed a light on future managements of such patients undergoing cardiac procedures with CPB. Pre-existing coagulopathies include antithrombin III deficiency, heparin-induced thrombocytopenia, cancer, factor XII deficiency, hemophilia, idiopathic thrombocytopenic purpura, protein S deficiency, and drug-induced platelet inhibition. In summary, pre-existing coagulopathy in patients undergoing open-heart surgeries, if not recognized and appropriately managed, can cause serious complications. Management of patients undergoing cardiac procedures should include a routine coagulation work-up and a thorough past medical history examination. If any of the foregoing is abnormal, further evaluation is warranted. Proper diagnosis and management of the pre-existing coagulopathy disorders is of crucial importance to the surgical outcome and long-term morbidity.