Corrosion Behavior of Detonation Gun Sprayed Fe-Al Type Intermetallic Coating

The detonation gun sprayed Fe-Al type coatings as an alternative for austenitic valve steel, were investigated using two different methods of testing corrosion resistance. High temperature, 10-hour isothermal oxidation experiments at 550, 750, 950 and 1100 °C show differences in the oxidation behavior of Fe-Al type coatings under air atmosphere. The oxide layer ensures satisfying oxidation resistance, even at 950 and 1100 °C. Hematite, α-Al₂O₃ and metastable alumina phases were noticed on the coatings top surface, which preserves its initial thickness providing protection to the underlying substrate. In general, only negligible changes of the phase composition of the coatings were noticed with simultaneous strengthening controlled in the micro-hardness measurements, even after 10-hours of heating at 1100 °C. On the other hand, the electrochemical corrosion tests, which were carried out in 200 ppm Cl⁻ (NaCl) and pH ~4 (H₂SO₄) solution to simulate the acid-rain environment, reveal higher values of the breakdown potential for D-gun sprayed Fe-Al type coatings than the ones for the bulk Fe-Al type alloy and Cr21Mn9Ni4 austenitic valve steel. This enables these materials to be used in structural and multifunctional applications in aggressive environments, including acidic ones.     

Survival from breast cancer in women with a BRCA2 mutation by treatment

Background The impact of various breast-cancer treatments on patients with a BRCA2 mutation has not been studied. We sought to estimate the impact of bilateral oophorectomy and other treatments on breast cancer-specific survival among patients with a germline BRCA2 mutation.Methods We identified 664 women with stage I–III breast cancer and a BRCA2 mutation by combining five different datasets (retrospective and prospective). Subjects were followed for 7.2 years from diagnosis to death from breast cancer. Tumour characteristics and cancer treatments were patient-reported and derived from medical records. Predictors of survival were determined using Cox proportional hazard models, adjusted for other treatments and for prognostic features.Results The 10-year breast-cancer survival for ER-positive patients was 78.9% and for ER-negative patients was 82.3% (adjusted HR = 1.23 (95% CI, 0.62–2.45, p = 0.55)). The 10-year breast-cancer survival for women who had a bilateral oophorectomy was 89.1% and for women who did not have an oophorectomy was 59.0% (adjusted HR = 0.45; 95% CI, 0.28–0.72, p = 0.001). The adjusted hazard ratio for chemotherapy was 0.83 (95% CI, 0.65–1.53: p = 0.56).Conclusions For women with breast cancer and a germline BRCA2 mutation, positive ER status does not predict superior survival. Oophorectomy is associated with a reduced risk of death from breast cancer and should be considered in the treatment plan.Subject terms: Targeted therapies, Breast cancer     

Co-occurrence of heterozygous CREB3L3 and APOA5 nonsense variants and polygenic risk in a patient with severe hypertriglyceridemia exacerbated by estrogen administration

We describe a case of a 36-year-old woman with severe hypertriglyceridemia likely caused by double heterozygosity of a known pathogenic APOA5 nonsense variant (p.Q275X) and a novel CREB3L3 nonsense variant (p.C296X) on a background of very strong polygenic susceptibility. Her clinical course worsened with development of eruptive xanthomata after oral administration of 2 mg estradiol twice daily for 2 weeks as part of a medical protocol for intrauterine embryo transfer following in vitro fertilization. Her triglyceride levels decreased to baseline and xanthomata resolved without treatment after discontinuation of hormonal therapy, which also resulted in termination of pregnancy. Before undergoing a second embryo transfer using her natural cycle and no exogenous hormones, the patient started combination therapy with eicosapentaenoic acid ethyl ester and gemfibrozil, leading to an ～80% decrease in triglyceride levels. She continued treatment throughout pregnancy, which progressed to term with the delivery of healthy twins.     

Usefulness of whole blood aggregometry and its comparison with thromboxane generation assay in monitoring acetylsalicylic acid effectiveness--a multiparametric study in rats.

BACKGROUND: There is a need for consensus concerning universal methodological criteria for detection of suboptimal response to acetylsalicylic acid (ASA) therapy. Therefore, animal models to test for ASA effectiveness remain of interest. Our objective was to verify the usefulness of multiparametric whole-blood impedance aggregometry and thromboxane A(2) generation, which are the most popular techniques used for monitoring of ASA treatment effectiveness. METHODS: Using multiparametric analysis of whole-blood impedance aggregometry, we examined which parameters of platelet aggregation or disaggregation allow for the best discrimination between ASA-treated (4 or 40 mg/kg for 60 days) and non-treated male rats. The effectiveness of ASA-mediated inhibition of platelet cyclooxygenase-1 was verified by determination of plasma thromboxane B(2) and urine 11-dehydro-thromboxane B(2), accepted as reference assays for monitoring of ASA-mediated platelet cyclooxygenase-1 inhibition. RESULTS: Two of the platelet agonists used, collagen (1 mg/L) and arachidonic acid (0.5 mmol/L), allowed discrimination of control and ASA-treated animals, whereas adenosine diphosphate (5 micromol/L) was not effective. It is noteworthy that only ASA-mediated changes in duration of the rising phase for platelet aggregation and the area under the curve for collagen-induced aggregation allowed significant discrimination between low and high ASA dose and remained correlated with the reference parameter, plasma thromboxane B(2). CONCLUSIONS: Analysis of aggregation curves, routinely based only on the amplitude and rate of platelet aggregation, may not be enough discriminative to distinguish between varying ASA doses and treatment schedules.     

CHEK2 mutations and the risk of papillary thyroid cancer

Mutations in the cell cycle checkpoint kinase 2 (CHEK2) tumor suppressor gene are associated with multi‐organ cancer susceptibility including cancers of the breast and prostate. A genetic association between thyroid and breast cancer has been suggested, however little is known about the determinants of this association. To characterize the association of CHEK2 mutations with thyroid cancer, we genotyped 468 unselected patients with papillary thyroid cancer and 468 (matched) cancer‐free controls for four founder mutations of CHEK2 (1100delC, IVS2 + 1G>A, del5395 and I157T). We compared the family histories reported by patients with a CHEK2 mutation to those of non‐carriers. A CHEK2 mutation was seen in 73 of 468 (15.6%) unselected patients with papillary thyroid cancer, compared to 28 of 460 (6.0%) age‐ and sex‐matched controls (OR 3.3; p < 0.0001). A truncating mutation (IVS2 + 1G>A, 1100delC or del5395) was associated with a higher risk of thyroid cancer (OR = 5.7; p = 0.006), than was the missense mutation I157T (OR = 2.8; p = 0.0001). CHEK2 mutation carriers reported a family history of breast cancer 2.2 times more commonly than non‐carriers (16.4% vs.8.1%; p = 0.05). A CHEK2 mutation was found in seven of 11 women (63%) with multiple primary cancers of the breast and thyroid (OR = 10; p = 0.0004). These results suggest that CHEK2 mutations predispose to thyroid cancer, familial aggregations of breast and thyroid cancer and to double primary cancers of the breast and thyroid.     

Factors influencing ovulation and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers

The role of the lifetime number of ovulatory cycles has not been evaluated in the context of BRCA‐associated ovarian cancer. Thus, we conducted a matched case–control study to evaluate the relationship between the cumulative number of ovulatory cycles (and contributing components) and risk of developing ovarian cancer in BRCA mutation carriers (1,329 cases and 5,267 controls). Information regarding reproductive and hormonal factors was collected from a routinely administered questionnaire. Conditional logistic regression was used to evaluate all associations. We observed a 45% reduction in the risk of developing ovarian cancer among women in the lowest vs. highest quartile of ovulatory cycles (OR = 0.55; 95% CI 0.41–0.75, p = 0.0001). Breastfeeding for more than 12 months was associated with a 38% (95% CI 0.48–0.79) and 50% (95% CI 0.29–0.84) reduction in risk among BRCA1 and BRCA2 mutation carriers, respectively. For oral contraceptive use, maximum benefit was seen with five or more years of use among BRCA1 mutation carriers (OR = 0.50; 95% CI 0.40–0.63) and three or more years for BRCA2 mutation carriers (OR = 0.42; 95% CI 0.22–0.83). Increasing parity was associated with a significant inverse trend among BRCA1 (OR = 0.87; 95% CI 0.79–0.96; p‐trend = 0.005) but not BRCA2 mutation carriers (OR 0.98; 95% CI 0.81–1.19; p‐trend = 0.85). A later age at menopause was associated with an increased risk in women with a BRCA1 mutation (OR trend = 1.18; 95% CI 1.03–1.35; p = 0.02). These findings support an important role of breastfeeding and oral contraceptive use for the primary prevention of ovarian cancer among women carrying BRCA mutations.     

Do determinants of platelet function co-segregate with genetic markers of type 1 diabetes mellitus?: Analysis of platelet and fibrinolytic parameters in families with type 1 diabetes mellitus

This study examined the significance of selected parameters of primary haemostasis to discriminate between relatives of children with insulin-dependent diabetes mellitus (IDDM). Platelet function, including markers of spontaneous and agonist-induced platelet activation (CD62), platelet consumption (microparticles) and clumping (aggregates), as well as selected parameters of the fibrinolytic system (t-PA and PAI-1), were studied in IDDM children (n = 45), their parents (n = 65), siblings (n = 17) and unrelated healthy controls (n = 51). The fraction of activated platelets circulating in whole blood amounted to 4.3±2.1% in IDDM children, and significantly exceeded the level found in parents (1.3±0.7%, P < 0.002), siblings (1.2±1.0%, P < 0.002), and controls (1.2±0.6%, P < 0.002). Furthermore, an enhanced formation of platelet microparticles was observed in the IDDM group, both in resting platelets and also when platelets were stimulated with thrombin. Significantly decreased total PAI-1 occurred in IDDM children (P < 0.02 versus parents); also slightly lowered active PAI-1 and t-PA antigen were noticed in IDDM subjects compared to other groups, however, the differences were not statistically significant. To assess dissimilarities between the groups of subjects we applied the forward stepwise model of discriminant function analysis, which included platelet flow cytometry parameters. The best separation and the highest discrepancy (expressed as the so called squared Mahalanobis distances, d_M) was revealed between controls and IDDM patients (P ? 0.0001) and between controls and parents (P ? 0.0001). The values of d_M found between IDDM children and their siblings (P < 0.001), as well as parents (P < 0.01), were of much lower significance. The finding that the control group, representing unrelated subjects, remains particularly well separated from the other groups, more or less clustered together, implies the possible involvement of genetic factor(s) which might potentially affect platelet activation and reactivity. In addition, the distinguished distribution of HLA DQAI⁵² and HLA DQBI⁵⁷ genotypes in the groups further validates the suspicion that the altered platelet function and response in diabetes might be associated with some independent genetic factor(s), and is not likely to result from HLA DQAI⁵² and HLA DQBI⁵⁷ impact.     

Late results of percutaneous balloon mitral commissurotomy in patients with restenosis after surgical commissurotomy compared to patients with 'de-novo' stenosis

BACKGROUND AND AIMS OF THE STUDY: The outcome of percutaneous balloon mitral commissurotomy (BMC) has been reported as poor in patients with prior surgical commissurotomy. The study aim was to evaluate immediate and long-term follow up results of BMC in patients with restenosis after surgical commissurotomy compared to patients with 'de-novo' mitral stenosis. METHODS: Between October 1988 and September 1999, a total of 1,027 patients underwent BMC. Of these patients, 169 (16.5%) were examined at 17+/-7 years (range: 2-33 years) after surgical commissurotomy (group 1), and 858 (83.5%) had de-novo mitral stenosis (group 2). RESULTS: Group 1 patients were older than group 2 patients (49.4+/-9.3 versus 47.3+/-9.6 years; p <0.05), and atrial fibrillation was seen more often in group 1 (53.9% versus 32.4%; p <0.005). Before BMC, mitral valve area (MVA) was similar in both groups (1.18+/-0.27 and 1.15+/-0.26 cm2 in groups 1 and 2 respectively; p = NS); following BMC, MVA was 1.82+/-0.3 and 1.93+/-0.40 cm2 respectively (p <0.05). Four patients (2.4%) from group 1, and 24 (2.8%) from group 2 required mitral valve replacement due to severe regurgitation (p = NS). Annual clinical and echocardiographic evaluation was completed for 950 patients (mean follow up 56.2+/-31.1 months (range: 12-132 months). Cardiac events defined as death, valve surgery or repeat BMC occurred in 16.0% of patients in group 1, and in 9.6% of those in group 2. At follow up of three, five and 10 years, actuarial event-free survival was 85.7+/-2.9%, 79.8+/-3.8% and 65.2+/-7.5% respectively in group 1, and 93.4+/-0.9%, 90.1+/-1.1% and 72.7+/-3.9% respectively in group 2 (log rank test, p = 0.02). Multivariate analysis showed MVA <1.5 cm2 after BMC, mitral regurgitation grade >2/4, Wilkins score >8, and mean transmitral gradient and left atrial mean pressure post BMC to be independent predictors of an adverse event occurring during follow up. CONCLUSION: BMC in patients with restenosis after surgical commissurotomy is an effective method of treatment, and may help to avoid valve surgery in most patients.     

Congenital murine osteopetrosis inherited with osteosclerotic (oc) gene: hematological characterization

Two- to three-week-old mice homozygous for the recessive oc gene had negligible numbers of marrow cells but possessed no significant spleno- and hepatomegaly. They also maintained normal numbers of blood cells except for monocytes, which were significantly lower. Additionally, they had reduced numbers of total cells and resident macrophages in the peritoneum, as determined by cell counts in the peritoneal lavage fluid. The frequency of spleen colony-forming units (CFU-S) in the spleens of oc/oc mice was the same as that in the spleens of normal littermate control mice. These oc/oc CFU-S showed essentially similar differentiation patterns as CFU-S of control mice. Also, a few CFU-S could be detected in livers of oc/oc mice. On the other hand, the frequency of cells that formed macrophage colonies in a four-day liquid-culture system in the presence of colony-stimulating activity was significantly reduced in oc/oc mice and abnormalities were observed in the formation of the adherent (stromal) layers by oc/oc spleen cells in liquid cultures. Numbers of fibroblastoid cell colonies in these layers were reduced and, moreover, cultures demonstrated a marked decrease in the number of macrophages both within and outside the fibroblastoid cell colonies. Transplants of spleen and thymus cells of oc/oc mice into lethally irradiated +/? recipients induced oc/oc-like lesions. They included peritoneal macrophage deficiency, marrow deficiency, as well as hepatosplenomegaly. This suggests a hemopoietic stem cell and not microenvironmental defect in this particular type of osteopetrosis. The murine mutant characterized in this study may be useful in studies of cellular interactions during blood and bone formation and in studies of the mononuclear phagocyte system.