Genotype–Phenotype Correlations by Ethnicity and Mutation Location in BRCA Mutation Carriers

The genotype–phenotype correlations of the specific BRCA1 and BRCA2 mutations in multi‐ethnic populations in USA have not yet been fully investigated. This study was designed to evaluate the effects of ethnicity at specific mutation locations and breast/ovarian cancer phenotypes. Our cohort included 445 women with different ethnic backgrounds who underwent BRCA genetic testing between 1997 and 2010. Known clinical and pathologic characteristics were compared with Chi‐Square Analysis or Fisher's Exact test as appropriate. The three most common mutation locations in BRCA1 (exons 2, 11, and 20) and BRCA2 (exons 10, 11, and 25) genes were chosen. Prevalence of BRCA1 exon 2 mutations were significantly higher in Ashkenazi Jewish (AJ) women compared to Caucasians (41% versus 15%; p = 0.001). Similarly, AJ women with breast cancer were more likely to have BRCA1 exon 2 mutation (47% positivity in AJ women versus 0–12.5% positivity in other ethnicities; p = 0.004). Women carrying the exon 20 BRCA1 mutation had the highest probability of having combined breast and ovarian cancers compared to women carrying other exon mutations (p = 0.05). The median age at initial cancer diagnosis, phenotypic features of breast cancer tumors, and overall survival did not vary significantly by ethnicity or mutation location. Our data suggest that ethnicity does not affect age of onset, overall survival or confer different risks of breast and ovarian cancer development in BRCA carriers. These results also suggest that women carrying the exon 20 BRCA1 mutation may warrant mutation‐specific counseling and be more aggressively managed for risk reduction.     

Influence of Ankaferd Blood Stopper on shear bond strength of bonding systems

This study investigated the effect of Ankaferd Blood Stopper (ABS) contamination on bond strength of total- and self-etching systems. Seventy mandibular third molars sectioned in a mesio-distal direction were mounted in acrylic resin, and flat dentin surfaces were exposed. The specimens were randomly assigned to seven groups (n=20), according to the surface treatment: Group I, ABS contamination+37% phosphoric acid+Solobond M; Group II, ABS contamination+Clearfil SE Bond; Group III, ABS contamination+All Bond SE; Group VI, 37% phosphoric acid+ABS contamination+Solobond M; Group V, Solobond M; Group VI, Clearfil SE Bond; and Group VII, All Bond SE. Next, a resin composite (Grandio) was built up using a plastic apparatus and polymerized. The specimens were tested in shear mode at a crosshead speed of 1 mm/min. There were significant differences in bond strengths between the control and ABS-contaminated samples. These findings suggest that ABS contamination reduced bond strength of total- and self-etching adhesives.     

Dose-dense chemotherapy for breast cancer

The concept of dose-dense chemotherapy has emerged and is based on the hypothesis that maximal chemotherapy effectiveness can be achieved by scheduling the interval of chemotherapy to correspond to the period of most rapid tumor growth, as predicted by preclinical models. The granulocyte-colony stimulating factor support has permitted the safe delivery of chemotherapy at shorter ("dose-dense") inter-treatment intervals. Several randomized trials have been conducted to test the feasibility and effectiveness of anthracycline and/or taxanes-based dose-dense strategies. They have been associated with a modest impact on disease recurrence and overall survival of patients with early-stage breast cancer. Subset analyses have suggested increased benefits for specific tumor subtypes such as hormone receptor-negative, highly proliferative or HER2 overexpressing tumors. This review article aims to outline the theoretical framework for dose-dense chemotherapy and summarizes the results of several recent clinical trials addressing this concept within neoadjuvant and adjuvant breast cancer treatment and discuss their implications for clinical practice. Further studies are needed to define the optimal regimen and the patient population that will receive the greatest benefit from dose-dense strategy.     

Effect of valproate and carbamazepine on visual evoked potentials in epileptic children

The effects of carbamazepine (CBZ) and sodium valproate (SV) monotherapy on visual evoked potentials (VEP) were studied in 18 epileptic children receiving CBZ and nine epileptic children receiving SV. Pattern reversal VEP were determined before the administration of antiepileptic drugs (AED) and 1 year later during which time the patients had received AED. The VEP amplitude showed no consistent changes after 1 year of CBZ and SV therapy, but VEP P-100 latencies were significantly prolonged after 1 year of CBZ therapy. We conclude that CBZ causes a slowing down of central impulse conduction and that VEP is useful to evaluate the effects of AED within the central nervous system.     

Induced abortion in the Nordic countries: special emphasis on young women

BACKGROUND: To analyze the trends in legally induced abortions among women younger than 30 years in the five Nordic countries, Denmark, Finland, Iceland, Norway and Sweden, since the liberalized abortion laws came into force. METHODS: Data stem from national registrations of vital events. Some have been published in the national vital statistics while others have been retrieved for this study. General and age-specific abortion rates are used to analyze the trends. Further, an index has been calculated by dividing the age-specific abortion rates by the Nordic average. RESULTS: The analysis reveals an overall reduction in the general abortion rates in the Nordic countries, apart from Iceland. The rates have been highest in Denmark and Sweden and lowest in Finland since the early 1980s. In the mid-1980s, the abortion rates increased among 15-19-year-old women in Sweden and among 20-24-year-old women in Denmark, Norway and Sweden, followed by a reduction. In Iceland the very low age-specific abortion rates for all age groups under 30 years at the beginning of the study period increased and Iceland had the highest rate for 15-19-year-old women in the late-1990s. CONCLUSIONS: The relatively low abortion rates in Finland demonstrate effective preventive efforts, although the recent increase challenges further studies on the relationship between abortion rates and counseling activities. The rise in abortion rates in Iceland indicate a need for improved sex education, contraceptive services and availability of contraceptive methods for young people.     

Endoneurial capillary abnormalities presage deterioration of glucose tolerance and accompany peripheral neuropathy in man

To explore whether microangiopathy is associated with disturbed glucose tolerance and peripheral neuropathy, we assessed endoneurial capillary morphology in sural nerve biopsies from men with diabetes, impaired glucose tolerance (IGT), and normal glucose tolerance (NGT). Baseline morphology was related to glucose tolerance and neuropathy at baseline and at follow-up 6 years later. Capillary density (in number per millimeters squared) at baseline was higher in subjects with diabetes (n = 10) compared with those with NGT (n = 5) at follow-up (median [interquartile range]) (86.0 [24.3] vs. 54.9 [17.1]; P = 0.0200) and in those progressing from IGT to diabetes (n = 4) compared with those with persistent IGT (n = 4) (86.7 [25.2] vs. 54.1 [14.6]; P = 0.0433). The capillary luminal area (in micrometers squared) was lower in subjects with NGT progressing to IGT (n = 2) or subjects with IGT progressing to diabetes (n = 3) compared with subjects with constant NGT (n = 6) or constant IGT (n = 4) (11.9 [2.4] vs. 20.8 [7.8]; P = 0.0201). The capillary basement membrane area (in micrometers squared) was increased in patients with peripheral neuropathy (n = 10) compared with those without (n = 7) (114.6 [68.8] vs. 75.3 [28.7]; P = 0.0084). In conclusion, increased capillary density was associated with current or future diabetes, decreased capillary luminal area with future deterioration in glucose tolerance, and increased basement membrane area with peripheral neuropathy.     

Secondary hematological malignancies following breast cancer treatment

Breast cancer (BC) incidence has increased among women in most Western countries. Concurrently, the survival time of BC patients has increased with 5-year survival rates reaching 80–90%. Secondary hematological malignancies (SHM) following BC treatment are an issue of concern to clinicians and also to patients and their families. However, therapy-induced leukemia after BC is an underemphasized clinical problem. In this review, we will focus on the incidences and patterns of occurrence of SHM in patients with BC. We will address risk factors for the development of SHM and we will explore how secondary hematological malignancies impact the survival of BC patients.     

Etiology and Antimicrobial Susceptibility of Middle Ear Fluid Pathogens in Costa Rican Children With Otitis Media Before and After the Introduction of the 7-Valent Pneumococcal Conjugate Vaccine in the National Immunization Program: Acute otitis media microbiology in Costa Rican children

Acute otitis media (AOM) microbiology was evaluated in children after 7-valent pneumococcal conjugate vaccine (PCV7) introduction in Costa Rica (private sector, 2004; National Immunization Program, 2009).This was a combined prospective and retrospective study conducted in a routine clinical setting in San José, Costa Rica. In the prospective part of the study, which was conducted post-PCV7 introduction (2010–2012), standard bacteriological procedures were used to evaluate the etiology and serotype distribution of middle ear fluid samples collected by tympanocentesis or otorrhea from children aged 3–59 months diagnosed with AOM. E-tests were used to evaluate antimicrobial susceptibility in culture-positive samples. Retrospective data recorded between 1999 and 2004 were used for comparison of bacterial etiology and serotype distribution before and after PCV7 introduction. Statistical significance was evaluated in bivariate analyses at the P-value < 0.05 level (without multiplicity correction).Post-PCV7 introduction, Haemophilus influenzae was detected in 118/456 and Streptococcus pneumoniae in 87/456 AOM episodes. Most H. influenzae isolates (113/118) were non-typeable. H. influenzae was more (27.4% vs 20.8%) and S. pneumoniae less (17.1% vs 25.5%) frequently observed in vaccinated (≥2 PCV7 doses or ≥1 PCV7 dose at >1 year of age) versus unvaccinated children. S. pneumoniae non-susceptibility rates were 1.1%, 34.5%, 31.7%, and 50.6% for penicillin, erythromycin, azithromycin, and trimethoprim/sulfamethoxazole (TMP-SMX), respectively. H. influenzae non-susceptibility rate was 66.9% for TMP-SMX. Between pre- and post-PCV7 introduction, H. influenzae became more (20.5% vs 25.9%; P-value < 0.001) and S. pneumoniae less (27.7% vs 19.1%; P-value = 0.002) prevalent, and PCV7 serotype proportions decreased among pneumococcal isolates (65.8% vs 43.7%; P-value = 0.0005). Frequently identified pneumococcal serotypes were 19F (34.2%), 3 (9.7%), 6B (9.7%), and 14 (9.7%) pre-PCV7 introduction, and 19F (27.6%), 14 (8.0%), and 35B (8.0%) post-PCV7 introduction.Following PCV7 introduction, a change in the distribution of AOM episodes caused by H. influenzae and pneumococcal serotypes included in PCV7 was observed in Costa Rican children. Pneumococcal vaccines impact should be further evaluated following broader vaccination coverage.     

The clonal analysis of anticardiolipin antibodies in a single patient with primary antiphospholipid syndrome reveals an extreme antibody heterogeneity

The mechanism underlying the prothrombotic state that characterizes the primary antiphospholipid syndrome proves to be difficult to define mainly because of the variety of the phospholipid and protein targets of antiphospholipid antibodies that have been described. Much of the debate is related to the use of polyclonal antibodies during the different antiphospholipid assays. To better describe the antiphospholipid antibodies, a strategy was designed to analyze the reactivity of each one antibody making up the polyclonal anticardiolipin activity, breaking down this reactivity at the clonal level. This was performed in a single patient with primary antiphospholipid syndrome by combining (1) the antigen-specific selection of single cells sorted by flow cytometry using structurally bilayered labeled anionic phospholipids and (2) the cloning of immunoglobulin (Ig) variable (V) region genes originating from individual IgG anticardiolipin-specific B cells by a single-cell polymerase chain reaction technique. The corresponding V regions were cloned in order to express human recombinant antibodies in insect cells by a baculovirus expression system. The molecular analysis, the fine specificity, and the protein cofactor dependency of the first 5 monoclonal IgG anticardiolipins are reported here. This clonal analysis reveals the extreme heterogeneity of these antibodies, which could account for the difficulties in the previous attempts to define the pathogenic antiphospholipid response. This approach should help to unravel the complex antiphospholipid immune response and the mechanism of the prothrombotic state associated with these antibodies, but it could also shed some light on their possible origins. (Blood. 2001;97:3820-3828)     

Gastric cancer: problems in histological diagnosis

The reproducibility of the most recent histological classifications for gastric cancer was studied. A comparison of the results obtained independently by both authors using the criteria of Lauren, Ming, Mulligan and WHO, showed that highest reproducibility was achieved with the WHO classification. However, an acceptable accuracy in diagnosis for the other three classifications was obtained. This study confirms the validity of the WHO criterion for initial diagnosis, while the other classifications should be kept for further specific investigations, such as epidemiological or prognostic studies.