Intensified shigellosis epidemic associated with sexual transmission in men who have sex with men - Shigella fexneri and s. Sonnei in England, 2004 to end of February 2015

Surveillance data suggest an intensification of the shigellosis epidemic associated with sexual transmission in men who have sex with men (MSM) in England with separate introductions into the population. In 2014, sexual transmission between MSM might have accounted for 97%, 89%, and 43% of non-travel associated Shigella flexneri 3a and S. flexneri 2a, and S. sonnei diagnoses. Clinicians should sensitively ascertain sexual history for men with enteric infections to facilitate prompt diagnosis and appropriate management

Use of gender distribution in routine surveillance data to detect potential transmission of gastrointestinal infections among men who have sex with men in England.

Detecting gastrointestinal (GI) infection transmission among men who have sex with men (MSM) in England is complicated by a lack of routine sexual behavioural data. We investigated whether gender distributions might generate signals for increased transmission of GI pathogens among MSM. We examined the percentage male of laboratory-confirmed patient-episodes for patients with no known travel history for 10 GI infections of public health interest in England between 2003 and 2013, stratified by age and region. An adult male excess was observed for Shigella spp. (annual maximum 71% male); most pronounced for those aged 25-49 years and living in London, Brighton and Manchester. An adult male excess was observed every year for Entamoeba histolytica (range 59.8-76.1% male), Giardia (53.1-57.6%) and Campylobacter (52.1-53.5%) and for a minority of years for hepatitis A (max. 69.8%) and typhoidal salmonella (max. 65.7%). This approach generated a signal for excess male episodes for six GI pathogens, including a characterised outbreak of Shigella among MSM. Stratified analyses by geography and age group were consistent with MSM transmission for Shigella. Optimisation and routine application of this technique by public health authorities elsewhere might help identify potential GI infection outbreaks due to sexual transmission among MSM, for further investigation

The pathology of familial breast cancer: Immunohistochemistry and molecular analysis

Extensive studies of BRCA1- and BRCA2-associated breast tumours have been carried out in the few years since the identification of these familial breast cancer predisposing genes. The morphological studies suggest that BRCA1 tumours differ from BRCA2 tumours and from sporadic breast cancers. Recent progress in immunohistochemistry and molecular biology techniques has enabled in-depth investigation of molecular pathology of these tumours. Studies to date have investigated issues such as steroid hormone receptor expression, mutation status of tumour suppressor genes TP53 and c-erbB2, and expression profiles of cell cycle proteins p21, p27 and cyclin D(1). Despite relative paucity of data, strong evidence of unique biological characteristics of BRCA1-associated breast cancer is accumulating. BRCA1-associated tumours appear to show an increased frequency of TP53 mutations, frequent p53 protein stabilization and absence of imunoreactivity for steroid hormone receptors. Further studies of larger number of samples of both BRCA1- and BRCA2-associated tumours are necessary to clarify and confirm these observations

Are Trp53 rescue of Brca1 embryonic lethality and Trp53/Brca1 breast cancer association related?

Brca1 is involved in multiple biological pathways including DNA damage repair, transcriptional regulation, and cell-cycle progression. A complex pattern of interactions of Brca1 with Trp53 has also emerged. Xu and coworkers found that haploid loss of Trp53 significantly reduces the embryonic lethality observed in mice with a homozygous in-frame deletion of Brca1 exon 11. They report that widespread apoptosis correlates with the embryonic lethality resulting from this homozygous Δ11 Brca1 mutation. A mechanism responsible for Brca1-associated carcinogenesis is proposed. These experiments extend our knowledge of a complex Brca1/Trp53 relationship. However, the precise mechanisms through which Brca1 interacts with Trp53 to suppress mammary tumor formation have yet to be elucidated

Treatment of non-small-cell lung cancer: a perspective on the recent advances and the experience with gefitinib

Worldwide, non-small-cell lung cancer (NSCLC) is a leading cause of cancer-related mortality and, until screening detects early disease, treatment for the majority of patients will consist of radiation therapy, chemotherapy or combinations thereof. Modern mono and doublet chemotherapy regimens have translated into modest increases in life expectancy and improved quality of life, but at the expense of systemic and pulmonary adverse events (AEs). There is a great unmet need to provide effective therapy for advanced NSCLC that does not have the toxicity burden of conventional chemotherapy and radiotherapy. Novel drugs that inhibit a range of growth factor receptors, such as the epidermal growth factor receptor tyrosine kinase inhibitors gefitinib (‘Iressa’) and erlotinib (‘Tarceva’) or the monoclonal antibody cetuximab (‘Erbitux’), have recently been evaluated. Having demonstrated antitumour activity and rapid symptom improvement in pretreated patients with advanced NSCLC, gefitinib was approved in the USA, Japan and other countries. Gefitinib is well tolerated with a low incidence of grade 3/4 AEs. Interstitial lung disease has been reported in a small number of patients receiving gefitinib, although this may be attributed to other treatments and conditions. Nevertheless, although the use of novel treatments requires vigilance for unexpected AEs such as pulmonary toxicity, in this area of high unmet clinical need, the benefits outweigh the risks in patients for whom no other proven effective treatment exists

The p53 pathway in breast cancer

p53 mutation remains the most common genetic change identified in human neoplasia. In breast cancer, p53 mutation is associated with more aggressive disease and worse overall survival. The frequency of mutation in p53 is, however, lower in breast cancer than in other solid tumours. Changes, both genetic and epigenetic, have been identified in regulators of p53 activity and in some downstream transcriptional targets of p53 in breast cancers that express wild-type p53. Molecular pathological analysis of the structure and expression of constituents of the p53 pathway is likely to have value in diagnosis, in prognostic assessment and, ultimately, in treatment of breast cancer

Cancer risk in close relatives of women with early-onset breast cancer – a population-based incidence study

Inherited susceptibility to breast cancer is associated with an early onset and bilateral disease. The extent of familial risks has not, however, been fully assessed in population-based incidence studies. The purpose of the study was to quantify the risks for cancers of the breast, ovary and other sites of close relatives of women in whom breast cancer was diagnosed at an early age. Records collected between 1943 and 1990 at the Danish Cancer Registry were searched, and 2860 women were found in whom breast cancer was diagnosed before age 40. Population registers and parish records were used to identify 14 973 parents, siblings and offspring of these women. Cancer occurrence through to 31 December 1993 was determined within the Cancer Registry's files and compared with national incidence rates. Women with early-onset breast cancer were at a nearly fourfold increased risk of developing a new cancer later in life (268 observed vs 68.9 expected). The excess risk was most evident for second cancer of the breast (181 vs 24.5) and for ovarian cancer (20 vs 3.3). For mothers and sisters, risks for cancers of the breast and ovary were significantly increased by two- to threefold. Bilateral breast cancer and breast–ovarian cancer were very strong predictors of familial risks, with one in four female relatives predicted to develop breast and/or ovarian cancer by age 75. Mothers had a slightly increased risk of colon cancer, but not endometrial cancer. The risk for breast cancer was also increased among fathers (standardized incidence ratio 2.5; 95% CI 0.5–7.4) and especially brothers (29; 7.7–74), although based on small numbers. The risk for prostatic cancer was unremarkable. In this large population-based survey, the first-degree relatives of women who developed breast cancer before age 40 were prone to ovarian cancer as well as male and female breast cancer, but not other tumours that may share susceptibility genes with breast cancer. © 1999 Cancer Research Campaig

Physician Attitudes towards Pharmacological Cognitive Enhancement: Safety Concerns Are Paramount

The ethical dimensions of pharmacological cognitive enhancement have been widely discussed in academic circles and the popular media, but missing from the conversation have been the perspectives of physicians - key decision makers in the adoption of new technologies into medical practice. We queried primary care physicians in major urban centers in Canada and the United States with the aim of understanding their attitudes towards cognitive enhancement. Our primary hypothesis was that physicians would be more comfortable prescribing cognitive enhancers to older patients than to young adults. Physicians were presented with a hypothetical pharmaceutical cognitive enhancer that had been approved by the regulatory authorities for use in healthy adults, and was characterized as being safe, effective, and without significant adverse side effects. Respondents overwhelmingly reported increasing comfort with prescribing cognitive enhancers as the patient age increased from 25 to 65. When asked about their comfort with prescribing extant drugs that might be considered enhancements (sildenafil, modafinil, and methylphenidate) or our hypothetical cognitive enhancer to a normal, healthy 40 year old, physicians were more comfortable prescribing sildenafil than any of the other three agents. When queried as to the reasons they answered as they did, the most prominent concerns physicians expressed were issues of safety that were not offset by the benefit afforded the individual, even in the face of explicit safety claims. Moreover, many physicians indicated that they viewed safety claims with considerable skepticism. It has become routine for safety to be raised and summarily dismissed as an issue in the debate over pharmacological cognitive enhancement; the observation that physicians were so skeptical in the face of explicit safety claims suggests that such a conclusion may be premature. Thus, physician attitudes suggest that greater weight be placed upon the balance between safety and benefit in consideration of pharmacological cognitive enhancement