Disordered small intestinal motility: a rational basis for toddlers'' diarrhoea

Toddler diarrhoea is the commonest cause of chronic diarrhoea without failure to thrive in childhood, but its pathogenesis remains obscure. We have studied upper small intestinal motility in three groups of children (control group 1 - children with no intestinal pathology undergoing duodenal intubation, n = 6; control group 2 - children with gastrointestinal pathology other than toddler diarrhoea, n = 11; control group 3 - children with toddler diarrhoea, n = 8). We studied fasting motor patterns and the response of the migrating motor complex to intravenous cholecystokinin and an intraduodenal bolus of 5% dextrose. The characteristics of the migrating motor complex in the three groups did not differ but their response to dextrose did. Intraduodenal dextrose disrupted the migrating motor complex in four out of four children in group 1; seven out of nine children in group 2; and nil of eight children with toddler diarrhoea in group 3. We suggest that this failure of intestinal motor response may play a major role in the pathogenesis of the diarrhoea in this condition.     

Screening for Chemical Contributions to Breast Cancer Risk: A Case Study for Chemical Safety Evaluation

Background

Current approaches to chemical screening, prioritization, and assessment are being reenvisioned, driven by innovations in chemical safety testing, new chemical regulations, and demand for information on human and environmental impacts of chemicals. To conceptualize these changes through the lens of a prevalent disease, the Breast Cancer and Chemicals Policy project convened an interdisciplinary expert panel to investigate methods for identifying chemicals that may increase breast cancer risk.

Methods

Based on a review of current evidence, the panel identified key biological processes whose perturbation may alter breast cancer risk. We identified corresponding assays to develop the Hazard Identification Approach for Breast Carcinogens (HIA-BC), a method for detecting chemicals that may raise breast cancer risk. Finally, we conducted a literature-based pilot test of the HIA-BC.

Results

The HIA-BC identifies assays capable of detecting alterations to biological processes relevant to breast cancer, including cellular and molecular events, tissue changes, and factors that alter susceptibility. In the pilot test of the HIA-BC, chemicals associated with breast cancer all demonstrated genotoxic or endocrine activity, but not necessarily both. Significant data gaps persist.

Conclusions

This approach could inform the development of toxicity testing that targets mechanisms relevant to breast cancer, providing a basis for identifying safer chemicals. The study identified important end points not currently evaluated by federal testing programs, including altered mammary gland development, Her2 activation, progesterone receptor activity, prolactin effects, and aspects of estrogen receptor β activity. This approach could be extended to identify the biological processes and screening methods relevant for other common diseases.

Citation

Schwarzman MR, Ackerman JM, Dairkee SH, Fenton SE, Johnson D, Navarro KM, Osborne G, Rudel RA, Solomon GM, Zeise L, Janssen S. 2015. Screening for chemical contributions to breast cancer risk: a case study for chemical safety evaluation. Environ Health Perspect 123:1255–1264; http://dx.doi.org/10.1289/ehp.1408337     

Investigating the relationship between HIV testing and risk behaviour in Britain: National Survey of Sexual Attitudes and Lifestyles 2000

OBJECTIVES: To estimate the prevalence of, and identify factors associated with, HIV testing in Britain. DESIGN: A large, stratified probability sample survey of sexual attitudes and lifestyles. METHODS: A total of 12,110 16-44 year olds completed a computer-assisted face-to-face interview and self-interview. Self-reports of HIV testing, i.e. the timing, reasons for and location of testing, were included. RESULTS: A total of 32.4% of men and 31.7% of women reported ever having had an HIV test, the majority of whom were tested through blood donation. When screening for blood donation and pregnancy were excluded, 9.0% of men and 4.6% of women had had a voluntary confidential HIV test (VCT) in the past 5 years. However, one third of injecting drug users and men who have sex with men had a VCT in the past 5 years. VCT in the past 5 years was significantly associated with age, residence, ethnicity, self-perceived HIV risk, reporting greater numbers of sexual partners, new sexual partners from abroad, previous sexually transmitted infection diagnosis, and injecting non-prescribed drugs for men and women, and same-sex partners (men only). Whereas sexually transmitted disease clinics were important sites for VCT, general practice accounted for almost a quarter of VCT. CONCLUSION: HIV testing is relatively common in Britain; however, it remains largely associated with population-based blood donation and antenatal screening programmes. In contrast, VCT remains highly associated with high-risk (sexual or drug-injecting) behaviours or population sub-groups at high risk. Strategies to reduce undiagnosed prevalent HIV infection will require further normalization and wider uptake of HIV testing.     

Lymphoproliferative responses to recombinant HIV-1 envelope antigens in neonates and infants receiving gp120 vaccines. AIDS Clinical Trial Group 230 Collaborators

Children of mothers infected with human immunodeficiency virus type 1 (HIV-1) were immunized at birth and at 1, 3, and 5 months with 1 of 3 doses of recombinant gp120 vaccines prepared from SF-2 or MN strains of HIV-1. A total of 126 children were not infected; 21 received adjuvant only. Vaccine recipients developed lymphoproliferative responses on >/=2 occasions, responding more often to homologous HIV-1 antigens than did adjuvant recipients (56% vs. 14%; P<.001). Responses were appreciated after 2 immunizations and were maintained for >84 weeks after the last immunization. An accelerated immunization schedule (birth, 2 weeks, 2 months, and 5 months) with the lowest dose of the SF-2 vaccine produced responses in all 11 vaccinees by 4 weeks. Responses to heterologous envelope antigens were also detected. Immune responses to vaccination are achievable at an age when some infection (perinatal or breast milk exposure related) may be prevented.     

Clofibric acid: a potential therapeutic agent in AML and MDS

Differentiation therapy using retinoic acids (RAs) or 1alpha25-dihydroxyvitamin D3 (D3) is an attractive alternative to chemotherapy in acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). However, with the exception of RA therapy for acute promyelocytic leukaemia (APL), RAs and D3 are not potent enough at doses that can be tolerated by patients. We demonstrate that clofibric acid (CA) enhances the response of HL60 cells to all-trans RA and D3. Our findings and those of others in the field lead us to suggest that combination therapy using all-trans RA and CA should be considered as potential therapy for AML and MDS.     

Screening, diagnosis and management of early syphilis in genitourinary medicine clinics in the UK

New diagnoses of syphilis in the UK increased eight-fold between 1997 and 2002. This study, conducted in 2002, demonstrated that 31% of clinics were not confident of their expertise to obtain an adequate specimen for dark ground microscopy (DGM), and 35% were not confident of their expertise to detect treponemes on DGM. In all, 64% of clinics had observed adherence problems in HIV-positive patients treated with parenteral regimens, as against 42% with oral regimens. Also, 51% of clinics waited more than a week for the results of initial serological tests for syphilis, and 88% of clinics waited more than a week for confirmatory test results. Other concerns include the failure to perform syphilis serology consistently whenever HIV-positive patients were at risk, and the widespread use of doxycycline as a therapy for syphilis in HIV-positive patients despite concerns that this is not known to be fully treponemicidal in cerebrospinal fluid.