Identification of thymidine nucleotidase and deoxyribonucleotidase activities among normal isozymes of 5''-nucleotidase in human erythrocytes.

The persistence of normal thymidine nucleotidase (ThyNase) activity in subjects with pyrimidine nucleotidase (PyrNase) deficiency suggested the possible existence of separate isozymes in normal human erythrocytes. This hypothesis was confirmed by studies of PyrNase-deficient individuals from five unrelated families. Erythrocytes deficient in PyrNase retained normal activity of an enzyme system preferentially active at pH 6.2 with a variety of 2'-deoxyribonucleoside 5'-monophosphate substrates, including those of uridine, thymidine, and cytidine. Lesser activities were observed with the corresponding ribonucleotides. Normal control hemolysates were also found capable of effectively dephosphorylating purine nucleotides (dAMP greater than AMP) when pH was lowered sufficiently from the pH 7.4-8.0 region commonly used in conventional assays. Variations in substrate specificity, pH optima, kinetics, and sensitivity to inactivation by Pb2+ indicated the existence of multiple 5'-nucleotidase isozymes in normal erythrocytes: PyrNase and deoxyribonucleotidase(s) that might function physiologically in the conversion of DNA-derived nucleotides to diffusible nucleosides. Evolution of such a unique 5'-nucleotidase suggests that normal erythroblast maturation and nuclear extrusion is accompanied by a degree of karyolysis sufficient to require dephosphorylation and clearance of DNA degradation products.     

Thrombus imaging in a primate model with antibodies specific for an external membrane protein of activated platelets.

The activated platelet is a potential target for the localization of thrombi in vivo since, after stimulation and secretion of granule contents, activated platelets are concentrated at sites of blood clot formation. In this study, we used antibodies specific for a membrane protein of activated platelets to detect experimental thrombi in an animal model. PADGEM (platelet activation-dependent granule-external membrane protein), a platelet alpha-granule membrane protein, is translocated to the plasma membrane during platelet activation and granule secretion. Since PADGEM is internal in unstimulated platelets, polyclonal anti-PADGEM and monoclonal KC4 antibodies do not bind to circulating resting platelets but do interact with activated platelets. Dacron graft material incubated with radiolabeled KC4 or anti-PADGEM antibodies in the presence of thrombin-activated platelet-rich plasma bound most of the antibody. Imaging experiments with 123I-labeled anti-PADGEM in baboons with an external arterial-venous Dacron shunt revealed rapid uptake in the thrombus induced by the Dacron graft; control experiments with 123I-labeled nonimmune IgG exhibited minimal uptake. Deep venous thrombi, formed by using percutaneous balloon catheters to stop blood flow in the femoral vein of baboons, were visualized with 123I-labeled anti-PADGEM. Thrombi were discernible against blood pool background activity without subtraction techniques within 1 hr. No target enhancement was seen with 123I-labeled nonimmune IgG. 123I-labeled anti-PADGEM cleared the blood pool with an initial half-disappearance time of 6 min and did not interfere with hemostasis. These results indicate that radioimmunoscintigraphy with anti-PADGEM antibodies can visualize thrombi in baboon models and is a promising technique for clinical thrombus detection in humans.     

Mucosal-associated invariant T cells and Vδ2+ γδ T cells in community acquired pneumonia: association of abundance in sputum with clinical severity and outcome

Mucosal-associated invariant T (MAIT) cells and Vδ2⁺ γδ T cells are anti-bacterial innate-like lymphocytes (ILLs) that are enriched in blood and mucosa. ILLs have been implicated in control of infection. However, the role of ILLs in community-acquired pneumonia (CAP) is unknown. Using sputum samples from a well-characterized CAP cohort, MAIT cell and Vδ2⁺ T cell abundance was determined by quantitative polymerase chain reaction (qPCR). Cytokine and chemokine concentrations in sputum were measured. The capacity of bacteria in sputum to produce activating ligands for MAIT cells and Vδ2⁺ T cells was inferred by 16S rRNA sequencing. MAIT cell abundance in sputum was higher in patients with less severe pneumonia; duration of hospital admission was inversely correlated with both MAIT and Vδ2⁺ T cell abundance. The abundance of both ILLs was higher in patients with a confirmed bacterial aetiology; however, there was no correlation with total bacterial load or the predicted capacity of bacteria to produce activating ligands. Sputum MAIT cell abundance was associated with interferon (IFN)-α, IFN-γ, and sputum neutrophil abundance, while Vδ2⁺ T cell abundance was associated with CXCL11 and IFN-γ. Therefore, MAIT and Vδ2⁺ T cells can be detected in sputum in CAP, where they may contribute to improved clinical outcome.     

Efficacy and safety of isradipine in hypertension

Of the calcium channel blocking drugs, only verapamil is approved in the United States for treatment of hypertension. Isradipine is a 1,4-dihydropyridine calcium blocker that may be given on a twice-daily basis. It causes peripheral vasodilation with minimal cardiodepressant activity. We undertook a double-blind, parallel group randomized, multicenter study of 203 hypertensive subjects to examine the efficacy and safety of isradipine in treatment of hypertension. Subjects were given 0, 2.5, 5, 7.5, or 10 mg isradipine twice daily for up to 5 weeks. There was a significant dose-response relationship between isradipine dose and decrease in systolic blood pressure (SBP) and diastolic blood pressure (DBP). Isradipine 15 mg/day reduced supine pressure by 16/15 mm Hg in patients with starting DBP less than 105 mm Hg and by 38/22 mm Hg in those with starting DBP greater than or equal to 105 mm Hg. There was no significant orthostatic fall in blood pressure at any dose. Heart rate (HR) increased on an average by only a maximum of four beats/min. The drug was slightly more effective in the elderly in the standing position than in the young in the standing position. Adverse effects were mild, and only six patients were discontinued from the study because of adverse effects. Isradipine appears to be a safe, effective drug in monotherapy of hypertension at a wide range of patient ages.     

Survey of health promotion organisational arrangements and levels of service for health promotion

This study was promoted by the Executive Committee of the Association of Directors of Public Health when faced with the need to examine the organisation of and quantify health promotion arrangements in the Health Districts of England and Wales, resulting from the concerns of many of the members of the Association. These concerns were based on the views that health promotion is a key purchasing function of the District Health Authorities and must be appropriately and effectively structured and adequately resourced if the requirements of The Health of The Nation are to be fulfilled.There are many aspects to health promotion work and the delivery of health promotion services which will need addressing in the new commissioning environment of the NHS. A need was recognised for up-to-date data about health promotion services to inform a necessary debate about future arrangements, since it appeared that organisational change was being driven by influences unconnected with the possibly most appropriate structure of health promotion departments and which relate to a contemporary view of health promotion. Reducing the size and cutting the cost of commissioning authorities was perceived as one of the most important influences. A postal questionnaire survey to all Health District and Regional Health Authorities in England and Wales was conducted covering questions about the present organisational arrangements and levels of service, and soliciting the opinions of those canvassed. A total of 185 District and Regional Health Authorities, effectively reduced to 171 because of mergers, was sent questionnaires, of which 141 were completed and returned, giving a response rate of 82.5%.Most Health Promotion Units are currently purchaser-only based or split betweenpurchaser and provider bases. The majority of Districts have an establishment for a Director of Health Promotion, who is likely to be based at the purchaser level, Most directors have support staff. The median staff level in this survey is 7 WTEs (whole-time equivalents), and the level for the population served is 2.74/100,000. A little over 50% of respondents felt that health promotion should be a split purchaser and provider function, and there is evidence that this opinion has changed in recent years. This reflects concern expressed in comments made by respondents about the practical problems inherent in the separation of the purchaser and provider elements of health promotion activities, resulting from the ostensible requirements of the purchaser/provider reorientation in the NHS. The survey provides a picture of the present organisational arrangements in health promotion across the country and forms a basis for discussion of future developments. It highlights the problems of integrating all health promotion functions under a single management umbrella, purchaser or provider, and of the perceived importance of ensuring an adequate health promotion structure at the commissioning level.     

Breastfeeding and the origins of health: Interdisciplinary perspectives and priorities

Breastfeeding and human milk (HM) are critically important to maternal, infant and population health. This paper summarizes the proceedings of a workshop that convened a multidisciplinary panel of researchers to identify key priorities and anticipated breakthroughs in breastfeeding and HM research, discuss perceived barriers and challenges to achieving these breakthroughs and propose a constructive action plan to maximize the impact of future research in this field. Priority research areas identified were as follows: (1) addressing low breastfeeding rates and inequities using mixed methods, community partnerships and implementation science approaches; (2) improving awareness of evidence‐based benefits, challenges and complexities of breastfeeding and HM among health practitioners and the public; (3) identifying differential impacts of alternative modes of HM feeding including expressed/pumped milk, donor milk and shared milk; and (4) developing a mechanistic understanding of the health effects of breastfeeding and the contributors to HM composition and variability. Key barriers and challenges included (1) overcoming methodological limitations of epidemiological breastfeeding research and mechanistic HM research; (2) counteracting ‘breastfeeding denialism’ arising from negative personal breastfeeding experiences; (3) distinguishing and aligning research and advocacy efforts; and (4) managing real and perceived conflicts of interest. To advance research on breastfeeding and HM and maximize the reach and impact of this research, larger investments are needed, interdisciplinary collaboration is essential, and the scientific community must engage families and other stakeholders in research planning and knowledge translation.     

A technique for control of hypertrophic scarring in the central region of the face

Various methods are available for applying pressure to the central portion of the face to reduce hypertrophic scarring after burn injury. Our center uses an elastomer insert with a thermoplastic backing, which is formed over a plaster mold of the patient's face. The insert is worn under a traditional anti-burn scar face mask. We reviewed the records of 26 patients with hypertrophic scarring to the central portion of the face to assess the effectiveness of the insert. Seventeen (65%) of these patients wore the insert until scar maturation. Three of these 17 patients later required reconstructive surgery of the central face. Our findings suggest that pressure to this part of the face may be effective in decreasing hypertrophic scar formation. The insert described in this article is inexpensive and relatively easy to fabricate.     

Excess hospital admissions for pneumonia and influenza in persons > or = 65 years associated with influenza epidemics in three English health districts: 1987-95

OBJECTIVES: To study the association between community influenza activity and acute hospital admissions for pneumonia and influenza among elderly persons. DESIGN: Multiple regression analysis of acute hospital admissions against community influenza activity, air temperature and seasonal and long-term trends. SETTING: Three English health districts: 1987-95. SUBJECTS: Persons aged > or = 65 years. OUTCOME MEASURES: Acute hospital admissions for pneumonia and influenza (ICD9: 480-487); excess hospital admissions during epidemic periods. RESULTS: The final regression model explained 70% of the total variation in hospital admissions for pneumonia and influenza, including 14% due to community influenza activity. However, most variation was explained by long-term and seasonal changes unrelated to influenza. In the large influenza epidemic of 1989/90 a typical health district (500,000 total population) experienced 56 excess admissions for pneumonia and influenza attributable to epidemic influenza among persons aged > or = 65 years, requiring 672 additional bed-days. However the figure varied widely between seasons and over the whole study period, the average winter excess was 17.5 admissions per health district, requiring an additional 210 bed-days. CONCLUSIONS: Influenza epidemics exert a variable impact on acute hospital admissions for pneumonia and influenza among elderly persons, which in the past have been poorly quantified. Although the absolute numbers of excess admissions is modest, their impact on bed availability may be considerable because of the duration of hospital stay in elderly persons.     

Telehealth consultations in rheumatology: cost-effectiveness and user satisfaction

We conducted a feasibility study to assess user satisfaction with and the cost-effectiveness of a rheumatology telehealth clinic in northern Alberta. Six telehealth clinics were organized between a rural health centre and the specialist rheumatology centre, which was about a 4 h drive away. Fifty-two new patients were seen. Their median age was 54 years (range 7-81 years). After the teleconsultation, no patient required a conventional face-to-face consultation. Overall, patients agreed that the teleconsultation met their needs and that the care they received was as good as conventional care. The physicians involved in the study thought the process practical and effective. The total costs of service delivery would be equal for teleconsultation and for traditional consultation at a workload of 247 consultations a year.     

Establishment of a smoking cessation programme in primary and secondary care in Canterbury

AIMS: Smokescreen for the 1990's is a smoking cessation programme devised for use in primary care in Australia. It is based on the 'readiness to change' model where smokers are categorised as being 'ready', 'unsure', or 'not ready' to quit smoking. Those in the 'ready' group are encouraged to set a quit date and offered nicotine replacement therapy. Those in the unsure group receive brief motivational intervention, and those 'not ready' are given simple health advice. The aims of the study were to evaluate the process and outcome of establishing this program in primary and secondary care in Christchurch. METHODS: Process evaluation involved all staff participating in the program. Patient outcomes including quit rates were assessed by interview six months after enrollment. RESULTS: Implementation was successful with 59 general practitioners, 49 practice nurses and 294 hospital staff receiving education in the use of the programme. Nine hundred and seven patients (smokers) were enrolled in the study, 347 from primary care and 560 from Christchurch Hospital. The point prevalence abstinence rate at 6 months was 10.4% for the primary care sample and 17% for the secondary care group, with an overall rate of 14.4%. CONCLUSIONS: The programme was successfully implemented across primary and secondary care with an acceptable quit rate at 6 months.