Peripheral adaptations to low blood flow in muscle during exercise

A reduction in muscle blood flow caused by central vascular or peripheral vascular disease, or both, invariably leads to a reduction in exercise tolerance. Exercise conditioning programs have been shown to be an effective means of improving exercise tolerance in many patients with cardiovascular disease. However, improvements can be found without detectable changes in total muscle blood flow during activity. This suggests that peripheral adaptations induced within active muscles by exercise training exert a beneficial influence. These adaptations could include (1) a redistribution of blood flow within the active muscle or limb, or both; (2) an enhanced capillary density within the active muscle; and (3) an increased mitochondrial content within the active muscle. Evaluation of these adaptations, in an animal model of peripheral arterial insufficiency, suggests that all 3 factors potentially serve to enhance exercise tolerance after training. The improved ability of trained muscle to accommodate the metabolic stress during contractions is noteworthy. These factors could contribute to the marked increase in endurance during mild submaximal exercise observed in patients after training.     

Functional depletion of T- and B-memory cells and other lymphoid cell subpopulations-during trypanosomiasis.

T. brucei infection in mice causes generalized immunosuppression with multiple changes in the cells of the lymphoid tissue. Loss of B cell responsiveness to antigens and mitogens, and the induction of suppressive T-cells and macrophages, have been previously reported (Hudson, Byner, Freeman & Terry, 1976; Corsini, Clayton, Askonas & Ogilvie, 1977; Jayawardena & Waksman, 1977). In this study, purified B- or T-cell populations from infected mice have been tested functionally in vitro or in vivo by transfer into syngeneic irradiated hosts to separate the cells from trypanosomes or their products. B-memory cells for thymus dependent (DNP-KLH) and thymus independent (DNP-Ficoll) antigens are depleted or lose their potential to respond to the antigen during T. brucei infection. Similarly, purified T-helper cells, and T-cells reactive to allogeneic target cells in mixed lymphocyte reactions are functionally defective. By 16 days of infection all these responses are less than 10% of the normal level. The loss of B-cell function follows the peak parasitaemia and is accompanied by increases in the serum levels of both IgM and IgG. Enhanced Ig production and decline in B-cell potential also occur in T-deprived mice and in CBA/N mice which lack a subset of T-independent B-cells. Cells affecting delayed hypersensitivity reactions retain their activity throughout trypanosome infection and so far provide the only exception to the general decline in immune potential.     

Immature dendritic cells generated with low doses of GM-CSF in the absence of IL-4 are maturation resistant and prolong allograft survival in vivo

Dendritic cells (DC) were cultured from mouse bone marrow (BM) progenitors in low concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) (GM(lo) DC) by two different protocols. The phenotype and functional properties of these GM(lo) DC were compared to those of standard BM-DC cultures generated in high concentrations of GM-CSF (GM(hi) DC) or in low GM-CSF plus IL-4 (GM(lo)/IL-4 DC). An effect of IL-4 on maturation was observed only at low but not high doses of GM-CSF. Compared to mature DC, GM(lo) DC were phenotypically immature, weak stimulators of allogeneic and peptide-specific T cell responses, but substantially more potent in presentation of native protein. Immature GM(lo) DC were resistant to maturation by lipopolysaccharide, TNF-alpha or anti-CD40 monoclonal antibodies, as the expression of co-stimulatory molecules was not increased, and stimulatory activity in oxidative mitogenesis was not enhanced. These maturation-resistant immature GM(lo) DC induced T cell unresponsiveness in vitro and in vivo. GM(lo) DC also prolonged haplotype-specific cardiac allograft survival (from 8 days to >100 days median survival time) when they were administered 7 days (but not 3, 14 or 28 days) before transplantation. Our findings may have important implications for future studies in T cell tolerance induction in vivo.     

Use of balloon dilatation to treat supravalvar pulmonary stenosis developing after anatomical correction for complete transposition.

Eight balloon dilatations were performed in five patients (aged from 10 to 37 months) in whom supravalvar pulmonary stenosis developed after anatomical correction for complete transposition. The ratio of the maximum diameter of the inflated balloon to the narrowest pulmonary arterial diameter varied from 1.6 to 3.3. In three patients with an initial ratio of less than or equal to 2 dilatation was repeated with a larger balloon. The right ventricular systolic pressure ranged from 0.70 to 1.25 of the simultaneously measured femoral arterial systolic pressure. The major stenosis was in the main pulmonary artery in four patients and at the pulmonary arterial bifurcation in one. After balloon angioplasty in the four patients there was no significant improvement in the ratio of right ventricular to femoral arterial systolic pressure or in the angiographic appearance. There was no change in the pressure ratio after angioplasty in the patient who had a major stenosis of the pulmonary arterial bifurcation and mild main pulmonary artery narrowing. There seemed to be a slight angiographic improvement in the bifurcation stenosis but at restudy two months later the angiographic improvement had disappeared. Balloon angioplasty of supravalvar pulmonary stenosis developing after anatomical correction for complete transposition was not successful in eight procedures. This lack of success may be attributable to a small pulmonary annulus with consequent multiple levels of stenosis and distortion of the main pulmonary artery.     

Polycystic Ovary Syndrome and Depression in New Zealand Adolescents

ObjectiveTo determine whether adolescents with polycystic ovary syndrome (PCOS) are more depressed than adolescent girls in the community and to examine factors associated with depression.DesignAn observational study comparing clinical and community samples.SettingTwo specialist reproductive endocrine clinics in Auckland, New Zealand.Participants102 girls aged 14-19 presenting for clinical assessment, fulfilling the Rotterdam consensus for PCOS. The comparison group was 1349 girls from a school-based survey of New Zealand youth.InterventionsClinically significant depression was identified by the long and short form Reynolds Adolescent Depression Scale. BMI, androgen levels, oral contraceptive use, objective symptom severity, age, ethnicity, and socioeconomic grouping were recorded.Main Outcome MeasuresClinically significant depression in the PCOS and community samples. Potential determinants of depression.ResultsClinically significant depression in adolescent girls with PCOS was not increased compared with the community sample (OR 1.3; 95%CI 0.7-2.7, P = .42). Within the PCOS cohort, depression was correlated with increased BMI (P = .01) and possibly acne (P = .08).ConclusionsLean adolescent girls with PCOS did not have more clinically significant depression than girls in the community. Within the PCOS cohort, however, there was a clear association between higher depression scores and elevated BMI. There is a potentially important interaction between obesity and depression in PCOS.     

Applied public health research - falling through the cracks?

Background  

There is a degree of dissonance between the types of evaluative research required by organisations providing or commissioning health care, those recommended by organisations developing evidence-based guidance, and those which research funding bodies are prepared to support.     

Observation of the cascaded atomic-to-global length scales driving protein motion

Model studies of the ligand photodissociation process of carboxymyoglobin have been conducted by using amplified few-cycle laser pulses short enough in duration (<10 fs) to capture the phase of the induced nuclear motions. The reaction-driven modes are observed directly in real time and depict the pathway by which energy liberated in the localized reaction site is efficiently channeled to functionally relevant mesoscale motions of the protein.     

Walk-in clinics: patient expectations and family physician availability

BACKGROUND: For over two decades, there has been controversy over the role and impact of walk-in clinics on primary health care. This study evaluates the providers' perspective on this topic. OBJECTIVE: The purpose of this qualitative study was to explore the perceptions and experiences of family physicians, emergency physicians and walk-in clinic physicians regarding the impact of walk-in clinics on Ontario's health care system. METHODS: The qualitative method of focus groups was used in this study. There were nine focus groups, each consisting of 4-9 participants, with a total of 63 physicians. The different practitioners (family physicians, emergency physicians, walk-in clinic physicians) attended separate focus groups. The focus groups explored the physicians' perceptions and experiences regarding the role and impact of walk-in clinics on Ontario's health care system. The focus groups were audio-taped and transcribed verbatim. The qualitative data analysis program NUD*IST was used to organize the data during the sequential thematic analysis. RESULTS: Factors contributing to the growth and evolution of walk-in clinics in Ontario were identified. These included a perceived increase in patients' expectations for convenient health care and a perceived decrease in the availability of family physicians. These factors created a gap in primary care which was filled by walk-in clinics. CONCLUSIONS: Participants' recommendations for narrowing this gap included an increase in both physician and patient accountability and changes to the current structure of primary health care delivery. These recommendations would either integrate walk-in clinics into the health care system or result in their elimination.