Age related IgG subclass response to respiratory syncytial virus fusion protein in infected infants

Respiratory syncytial virus (RSV) fusion protein was purified by immunoaffinity chromatography using a mouse monoclonal antibody coupled to Affi-gel 10. The fusion protein was homogeneous by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and free of other detectable viral or cellular protein. The purified fusion protein was used in a quantitative enzyme-linked immunosorbent assay (ELISA) to measure the age-related antibody response to this protein in infected infants. The four IgG subclasses, IgA and IgM levels were determined for infants under 6 months of age, infants aged 6 months to 1 year and infants aged 1 year and over. Most infants over 6 months of age showed marked increases in both IgG1 and IgG3 antibodies with poor or negligible response with IgG2 and IgG4. By contrast infants under 6 months failed to respond by the production of IgG antibodies, although increases in IgA and IgM levels were observed. These data may explain the failure of primary RSV infections to induce protective immunity and have implications for the strategic use of attenuated RSV vaccines.     

Autoradiographic localization of kappa opiate receptors in CNS taste and feeding areas

Recent evidence suggests that kappa opiate receptors may play a key role in the regulation of appetite. Such evidence implies that kappa receptors might be localized within specific brain areas known to regulate ingestive behaviors. On the basis of this implication we employed an in vitro film autoradiographic technique using 3H-ethylketocyclazozine as ligand to identify putative kappa receptors within CNS "taste" nuclei and surrounding areas. Coronal cryostat sections of rat brain were incubated with ligand in the presence of D-Ala2, D-Leu5-enkephalin (DADLE) and morphine, apposed to LKB Ultrofilm for 60 days, processed and kappa receptor densities evaluated with the aid of a hand held photometer and video image analyzer. Highest kappa receptor densities were found within various gustatory and feeding sites including the rostral pole of the nucleus of the solitary tract, parabrachial nuclei, ventral posterior and medial portions of the thalamus, medial hypothalamus, medial nuclei of the amygdala and bed nucleus of the stria terminalis. Various other midline and medial limbic areas also showed significant kappa densities.     

The clinical pharmacokinetics of the novel antifolate N10-propargyl-5,8-dideazafolic acid (CB 3717)

Summary The pharmacokinetics of the new antifolate CB 3717 were studied in 20 patients during its phase-I clinical evaluation. The drug was administered at doses of 100–550 mg/m² in 1-h and 12-h infusions, resulting in peak plasma concentrations of CB 3717 of 40–200 M. There was a linear relationship between the dose and both CB 3717 AUC and peak plasma levels. Following a 1-h infusion, drug levels in the plasma decayed biphasically (t_1/2=49±9 min, t_1/2=739±209 min). 27%±2% of the dose was excreted in urine in the 24-h period after treatment, suggesting that the major route of elimination was via the bile. Furthermore, the parent compound CB 3717 and its desglutamyl metabolite, CB 3751, were found in a faecal collection although the metabolite was not detected in plasma or urine samples. Plasma protein binding of CB 3717 was extensive (97.6%±0.1%). Significant quantities of CB 3717 penetrated into ascitic fluid but not into cerebrospinal fluid.Residual drug was detected in postmortem kidney tissue from a patient who died of progressive disease 8 days after treatment with 330 mg/m² CB 3717. Thus, dose-limiting renal toxicity (maximum tolerated dose 600 mg/m²) may be due to drug precipitation in the renal tubules. Elevation of liver enzymes, in particular transaminases, occurred frequently as a toxic manifestation of CB 3717 therapy. In 11 patients studied after their first treatment there was a positive correlation between the rise in serum alanine transaminase and peak drug levels (r=0.69, P=0.02)These pharmacokinetic studies have shown that, by analogy with experimental systems, cytotoxic plasma levels of CB 3717 are archieved in man. In addition, they have been valuable in interpreting toxicities observed during phase-I clinical studies.This work was supported by grants from the Medical Research Council and Cancer Research Campaign, U. K.     

Community involvement in health promotion: progress or panacea?

There are many arenas within which health promotion may be located. This paper addresses the issues involved in the development of health promotion in one such arena: the community health movement. This movement is complex and dynamic. When reference is made to non-statutory health action, or to community involvement in health, this complexity may not be fully appreciated. There is a tendency for the range of activity to be reduced to its most "visible" form: self-help activity. However, there is more to the community health movement than this. A typology is offered here in which three levels of community-based activity in Britain are identified. These are referred to as self-help groups, community health groups and community development health projects. The breadth and range of this activity reflects the inability of formalized health care to tackle many of the underlying causes of ill-health. Each type of community health activity exists as a declaration of this failure, but some forms of activity may be welcomed by the health professions whilst others may not. In particular the numerically small community development health projects offer a significant challenge to formal health care because they seek to encourage collective health activity by those who are least in control of their own health. It is within the context of developing strategies for health promotion that community health action is most relevant. National and local strategy documents suggest that community involvement is essential for the successful promotion of health. Fully comprehensive participation by community groups signifies a major shift in our perceptions of health and health care. An appreciation of the existing range of health action in communities is an important starting point for medical health professionals engaged in this task.     

Determinants and Inequities in Sexual and Reproductive Health (SRH) Care Access Among Im/Migrant Women in Canada: Findings of a Comprehensive Review (2008–2018)

Given growing concerns of im/migrant women’s access to sexual and reproductive health (SRH) services, we aimed to (1) describe inequities and determinants of their engagement with SRH services in Canada; and (2) understand their lived experiences of barriers and facilitators to healthcare. Using a comprehensive review methodology, we searched the quantitative and qualitative peer-reviewed literature of im/migrant women’s access to SRH care in Canada from 2008 to 2018. Of 782 studies, 38 met inclusion criteria. Ontario (n?=?18), British Columbia (n?=?6), and Alberta (n?=?6) were primary settings represented. Studies focused primarily on maternity care (n?=?20) and sexual health screenings (n?=?12). Determinants included health system navigation and service information; experiences with health personnel; culturally safe and language-specific care; social isolation and support; immigration-specific factors; discrimination and racialization; and gender and power relations. There is a need for research that compares experiences across diverse groups of racialized im/migrants and a broader range of SRH services to inform responsive, equity-focused programs and policies.

     

Pretransplant solid organ malignancy and organ transplant candidacy: A consensus expert opinion statement

Patients undergoing evaluation for solid organ transplantation (SOT) often have a history of malignancy. Although the cancer has been treated in these patients, the benefits of transplantation need to be balanced against the risk of tumor recurrence, especially in the setting of immunosuppression. Prior guidelines of when to transplant patients with a prior treated malignancy do not take in to account current staging, disease biology, or advances in cancer treatments. To develop contemporary recommendations, the American Society of Transplantation held a consensus workshop to perform a comprehensive review of current literature regarding cancer therapies, cancer stage-specific prognosis, the kinetics of cancer recurrence, and the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis based on contemporary treatment and transplant recommendations for breast, colorectal, anal, urological, gynecological, and nonsmall cell lung cancers. This conference and consensus documents aim to provide recommendations to assist in the evaluation of patients for SOT given a history of a pretransplant malignancy.     

Liver transplantation for acute liver failure in a SARS-CoV-2 PCR-positive patient

Current guidelines recommend deferring liver transplantation (LT) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until clinical improvement occurs and two PCR tests collected at least 24 hours apart are negative. We report a case of an 18-year-old, previously healthy African-American woman diagnosed with COVID-19, who presents with acute liver failure (ALF) requiring urgent LT in the context of SARS-CoV-2 polymerase chain reaction (PCR) positivity. The patient was thought to have acute Wilsonian crisis on the basis of hemolytic anemia, alkaline phosphatase:bilirubin ratio <4, AST:ALT ratio >2.2, elevated serum copper, and low uric acid, although an unusual presentation of COVID-19 causing ALF could not be excluded. After meeting criteria for status 1a listing, the patient underwent successful LT, despite ongoing SARS-CoV-2 PCR positivity. Remdesivir was given immediately posttransplant, and mycophenolate mofetil was withheld initially and the SARS-CoV-2 PCR test eventually became negative. Three months following transplantation, the patient has made a near-complete recovery. This case highlights that COVID-19 with SARS-CoV-2 PCR positivity may not be an absolute contraindication for transplantation in ALF. Criteria for patient selection and timing of LT amid the COVID-19 pandemic need to be validated in future studies.     

Community care staff attitudes towards delivering a falls prevention exercise intervention to community care clients

Millions of older people world-wide receive community care services in their home to assist them to live independently. These services often include personal care, domestic assistance and social support which are delivered by non-university trained staff, and are frequently long term. Older people receiving community care services fall 50% more often than individuals of similar age not receiving services. Yet, few ongoing community care services include exercise programs to reduce falls in this population. We conducted an earlier study to examine the feasibility of community care staff delivering a falls prevention program. A critical finding was that while some of the assessment and support staff responsible for service delivery delivered the falls prevention exercise program to one or two clients, others delivered to none. Therefore, the aim of this qualitative sub-study was to understand reasons for this variation. Semi-structured interviews were conducted with 25 participating support staff and assessors from 10 community care organisations. Staff who had successfully delivered the intervention to their clients perceived themselves as capable and that it would benefit their clients. Older clients who were positive, motivated and wanted to improve were perceived to be more likely to participate. Staff who had worked at their organisation for at least 5 years were also more likely to deliver the program compared to those that had only worked up to 2 years. Staff that did not deliver the intervention to anyone were more risk averse, did not feel confident enough to deliver the program and perceived their clients as not suitable due to age and frailty. Experienced staff who are confident and have positive ageing attitudes are most likely to deliver falls prevention programs in a home care organisation.