Presence of lead in opium.

Opium addiction is a common form of addiction in Middle East countries such as Iran. Recently several reports suggested some kinds of pathologic findings such as abdominal pain, nephropathy, and anemia in opium addict patients. Such pathologic findings suggest lead poisoning in the patients. In this study, the concentration of lead in 10 opium samples was evaluated. The mean concentration of lead in the opium samples was 1.88 ppm. This may explain some of the pathologic findings found in addict patients. The authors would suggest further investigations to evaluate the lead concentration in opium addicts' sera and also routine screening for lead poisoning in opium addict patients

‘It is not a quick fix’ structural and contextual issues that affect implementation of integrated health and well-being services: a qualitative study from North East England

Objective The objective of this article is to examine the factors affecting the design, commissioning and delivery of integrated health and well-being services (IHWSs), which seek to address multiple health-related behaviours, improve well-being and tackle health inequalities using holistic approaches. Study design Qualitative studies embedded within iterative process evaluations. Methods Semi-structured interviews conducted with 16 key informants as part of two separate evaluations of IHWSs in North East England, supplemented by informal observations of service delivery. Transcripts and fieldnotes were analysed thematically. Results The study findings identify a challenging organisational context in which to implement innovative service redesign, as a result of budget cuts and changes in NHS and local authority capacity. Pressures to demonstrate outcomes affected the ability to negotiate the practicalities of joint working. Progress is at risk of being undermined by pressures to disinvest before the long-term benefits to population health and well-being are realised. The findings raise important questions about contract management and relationships between commissioners and providers involved in implementing these new ways of working. Conclusions These findings provide useful learning in terms of the delivery and commissioning of similar IHWSs, contributing to understanding of the benefits and challenges of this model of working

A phase II trial of murine monoclonal antibody 17-1A and interferon-γ: clinical and immunological data

A group of 15 patients with metastatic colorectal adenocarcinoma received a combination of interferon γ (0.1 mg/m2, days 1–15) and the murine monoclonal antibody 17-1A (400 mg, days 5, 7, 9 and 12). The treatment was tolerated with minimal toxicity. Of the 14 evaluable patients, 13 developed human antibody to murine 17-1A, with 11 patients demonstrating antibody to the variable region of 17-1A (anti-idiotype). Antibody to the variable region was inhibited by 17-1A but not by mouse immunoglobulin. Sera from patients with substantial anti-idiotype reactivity were capable of inhibiting the binding of murine 17-1A to antigen expressing LS174-T cells thus indicating the presence of antibody directed against the 17-1A combining site (mirror-image anti-idiotype). The median survival of the whole group was 56 weeks and there was no correlation between clinical response/survival and the development of anti-idiotype antibody

Phase I trial of iodine-131-chimeric B72. 3 (human IgG4) in metastatic colorectal cancer

Twelve patients with metastatic colorectal cancer participated in a Phase I trial of 1311-labeled chimeric B72.3 (human IgG4). Consecutive groups of patients received 18 mCi/m 2, 27 mCi/ m 2 and 36 mCi/m a. No acute side effects related to antibody administration were noted. Bone marrow suppression was the only side effect; it was dose-dependent and correlated with whole-body radiation dose estimates. The lowest dose level produced no marrow suppression, whereas 27 mCi/m 2 resulted in Grade 1 and 2 marrow suppression in two of three patients. The maximum tolerated close was 36 mCi/m 2 with all six patients at this dose level having at least Grade 1 and two patients with Grade 3 and 4 marrow suppression. Eight of 12 patients had radioimmune imaging of tumor sites at 5- 22 days. Seven patients had an antibody response to initial infusion. On retreatment, whole-body kinetics and imaging were altered for patients with a high anti-ch-B72.3 response. Thus, chimeric B72.3 (IgG4) has limited utility as a means of delivering multiple therapeutic doses of 1311 in the majority of patients; alternative strategies including second generation anti-TAG-72 monoclonal antibodies, other radioisotopes and other chimeric human isotypes will need to be pursued

Phase I trial of the murine monoclonal anti-GD2 antibody 14G2a in metastatic melanoma

In a phase I trial, 12 patients with GD2 antigen-positive metastatic melanoma received the murine anti-GD2 monoclonal antibody 14G2a. The monoclonal antibody was administered in four doses over an 8-day period with total dose ranging from 10 to 120 mg. All patients receiving \u3e10 mg of 14G2a experienced transient abdominal/pelvic pain during the antibody infusion. Five patients had a delayed extremity pain syndrome following the third and fourth antibody infusion. Four of the five patients developed neurological toxicity, including two patients with significant although reversible motor neuropathy. Two of the patients developed hyponatremia secondary to a syndrome of inappropriate antidiuretic hormone. All 12 patients developed high levels of human anti-14G2a antibody. The plasma half-life of 14G2a was 42 ± 6 (SD) h. One patient each had a partial response, mixed response, and stable disease, respectively. The very modest antitumor activity accompanied by dose-limiting neurological toxicity at total doses \u3e80 mg may restrict the clinical utility of murine 14G2a

"It was the whole picture" a mixed methods study of successful components in an integrated wellness service in North East England

Background A growing number of Local Authorities (LAs) have introduced integrated wellness services as part of efforts to deliver cost effective, preventive services that address the social determinants of health. This study examined which elements of an integrated wellness service in the north east of England were effective in improving health and wellbeing (HWB). Methods The study used a mixed-methods approach. In-depth semi-structured interviews (IVs) were conducted with integrated wellness service users (n = 25) and focus groups (FGs) with group based service users (n = 14) and non-service users (n = 23) to gather the views of stakeholders. Findings are presented here alongside analysis of routine monitoring data. The different data were compared to examine what each data source revealed about the effectiveness of the service. Results Findings suggest that integrated wellness services work by addressing the social determinants of health and respond to multiple complex health and social concerns rather than single issues. The paper identifies examples of ‘active ingredients’ at the heart of the programme, such as sustained relationships, peer support and confidence building, as well as the activities through which changes take place, such as sports and leisure opportunities which in turn encourage social interaction. Wider wellbeing outcomes, including reduced social isolation and increased self-efficacy are also reported. Practical and motivational support helped build community capacity by encouraging community groups to access funding, helped navigate bureaucratic systems, and promoted understanding of marginalised communities. Fully integrated wellness services could support progression opportunities through volunteering and mentoring. Conclusions An integrated wellness service that offers a holistic approach was valued by service users and allowed them to address complex issues simultaneously. Few of the reported health gains were captured in routine data. Quantitative and qualitative data each offered a partial view of how effectively services were working

Embedded Research::a promising way to create evidence-informed impact in public health?

Background Embedded research (ER) is recognized as one way to strengthen the integration of evidence into public health (PH) practice. In this paper, we outline a promising example of the co-production of research evidence between Fuse, the UKCRC Centre for Translational Research in Public Health and a local authority (LA) in north east England. Methods We critically examine attempts to share and use research findings to influence decision-making in a LA setting, drawing on insights from PH practitioners, managers, commissioners and academic partners involved in this organizational case study. We highlight what can be achieved as a co-located embedded researcher. Results The benefits and risks of ER are explored, alongside our reflections on the added value of this approach and the institutional prerequisites necessary for it to work. We argue that while this is not a new methodological approach, its application in PH as a way to facilitate evidence use is novel, and raises pragmatic and theoretical questions about the nature of impact and the extent to which it can be engineered. Conclusion With increased situated understanding of organizational culture and norms and greater awareness of the socio-political realities of PH, ER enables new co-produced solutions to become possible

Deletion of the Mitochondrial Superoxide Dismutase sod-2 Extends Lifespan in Caenorhabditis elegans

The oxidative stress theory of aging postulates that aging results from the accumulation of molecular damage caused by reactive oxygen species (ROS) generated during normal metabolism. Superoxide dismutases (SODs) counteract this process by detoxifying superoxide. It has previously been shown that elimination of either cytoplasmic or mitochondrial SOD in yeast, flies, and mice results in decreased lifespan. In this experiment, we examine the effect of eliminating each of the five individual sod genes present in Caenorhabditis elegans. In contrast to what is observed in other model organisms, none of the sod deletion mutants shows decreased lifespan compared to wild-type worms, despite a clear increase in sensitivity to paraquat- and juglone-induced oxidative stress. In fact, even mutants lacking combinations of two or three sod genes survive at least as long as wild-type worms. Examination of gene expression in these mutants reveals mild compensatory up-regulation of other sod genes. Interestingly, we find that sod-2 mutants are long-lived despite a significant increase in oxidatively damaged proteins. Testing the effect of sod-2 deletion on known pathways of lifespan extension reveals a clear interaction with genes that affect mitochondrial function: sod-2 deletion markedly increases lifespan in clk-1 worms while clearly decreasing the lifespan of isp-1 worms. Combined with the mitochondrial localization of SOD-2 and the fact that sod-2 mutant worms exhibit phenotypes that are characteristic of long-lived mitochondrial mutants—including slow development, low brood size, and slow defecation—this suggests that deletion of sod-2 extends lifespan through a similar mechanism. This conclusion is supported by our demonstration of decreased oxygen consumption in sod-2 mutant worms. Overall, we show that increased oxidative stress caused by deletion of sod genes does not result in decreased lifespan in C. elegans and that deletion of sod-2 extends worm lifespan by altering mitochondrial function

Quantitative and Molecular Genetic Analyses of Mutations Increasing Drosophila Life Span

Understanding the genetic and environmental factors that affect variation in life span and senescence is of major interest for human health and evolutionary biology. Multiple mechanisms affect longevity, many of which are conserved across species, but the genetic networks underlying each mechanism and cross-talk between networks are unknown. We report the results of a screen for mutations affecting Drosophila life span. One third of the 1,332 homozygous P–element insertion lines assessed had quantitative effects on life span; mutations reducing life span were twice as common as mutations increasing life span. We confirmed 58 mutations with increased longevity, only one of which is in a gene previously associated with life span. The effects of the mutations increasing life span were highly sex-specific, with a trend towards opposite effects in males and females. Mutations in the same gene were associated with both increased and decreased life span, depending on the location and orientation of the P–element insertion, and genetic background. We observed substantial—and sex-specific—epistasis among a sample of ten mutations with increased life span. All mutations increasing life span had at least one deleterious pleiotropic effect on stress resistance or general health, with different patterns of pleiotropy for males and females. Whole-genome transcript profiles of seven of the mutant lines and the wild type revealed 4,488 differentially expressed transcripts, 553 of which were common to four or more of the mutant lines, which include genes previously associated with life span and novel genes implicated by this study. Therefore longevity has a large mutational target size; genes affecting life span have variable allelic effects; alleles affecting life span exhibit antagonistic pleiotropy and form epistatic networks; and sex-specific mutational effects are ubiquitous. Comparison of transcript profiles of long-lived mutations and the control line reveals a transcriptional signature of increased life span