HCO 3 − -dependent ACh-activated Na+ influx in sheep parotid secretory endpieces

In the present study we used the Na⁺-sensitive fluorescent dye SBFI and optical measurement of endpiece volume to investigate the transport of Na⁺ in sheep parotid secretory cells. Sheep parotid endpiece cells bathed in a HCO ₃ ^– -free Cl^–-rich solution had a resting intracellular Na⁺ concentration ([Na⁺]_i) of 17±2 mmol/l (n=39). Exposure of the cells to a 2-min pulse of acetylcholine (ACh) (3×10^–7 mol/l) in a HCO ₃ ^– -free bathing solution produced no change in [Na⁺]_i or in cell volume. Changing from a Cl^–-containing HCO ₃ ^– -free bath solution to a Cl^– solution containing 25 mmol/l HCO ₃ ^– caused the endpieces to swell by 8±2 % (n=11) and the [Na⁺]_i to increase by 10±2 mmol/l (n=14). Subsequent exposure of the cells to ACh led to shrinkage of the cells by 12±2 % from the volume in the HCO ₃ ^– -containing solution prior to ACh exposure, with the maximum decrease occurring after 29±7 s (n=9). This shrinkage was accompanied by a rapid and transient increase in [Na⁺]_i, the [Na⁺]_i reaching a peak at 70±5 mmol/l above the unstimulated level (n=9). Substitution of gluconate for Cl^– did not significantly alter the effects of HCO ₃ ^– on unstimulated [Na⁺]_i or endpiece volume, nor did it significantly inhibit the effects of ACh on these two parameters when HCO ₃ ^– was present. Addition of 200 mol/l dihydrogen-4,4-diisothiocyanatostilbene-2,2-disulfonic acid (H₂-DIDS) to the gluconate/HCO ₃ ^– solution significantly reduced the peak of the ACh-induced increase in [Na⁺]_i to 34±10 mmol/l (n=4), but did not have any significant effect on the magnitude of the ACh-induced shrinkage. At 500 mol/l, H₂-DIDS abolished the ACh-induced increase in [Na⁺]_i and also significantly reduced the shrinkage due to ACh. Finally, we found that the rate of endpiece shrinkage following ACh stimulation did not depend on the presence of Cl^–.We interpret these results as indicating that sheep parotid secretory cells do not contain significant Na⁺-K⁺-2Cl^– co-transport activity and do not actively accumulate Cl^–. Rather, the mechanism of spontaneous basal secretion by these cells, in the presence of extracellular HCO ₃ ^– , is based on the accumulation of HCO ₃ ^– by the Na⁺-H⁺ exchanger. During ACh stimulation, the concentration of HCO ₃ ^– in the cytosol is also maintained by the operation of a H₂-DIDS-sensitive Na⁺-HCO ₃ ^– co-transporter. HCO ₃ ^– efflux across the apical membrane occurs via a HCO ₃ ^– conductance pathway rather than by the coupled operation of a Cl^– channel and a Cl^–-HCO ₃ ^– exchanger.     

Quality of diabetes care in community health centers

OBJECTIVES: This study assessed the quality of diabetes care in community health centers. METHODS: In 55 midwestern community health centers, we reviewed the charts of 2865 diabetic adults for American Diabetes Association measures of quality. RESULTS: On average, 70% of the patients in each community health center had measurements of glycosylated hemoglobin, 26% had dilated eye examinations, 66% had diet intervention, and 51% received foot care. The average glycosylated hemoglobin value per community health center was 8.6%. Practice guidelines were independently associated with higher quality of care. CONCLUSIONS: Rates of adherence to process measures of quality were relatively low among community health centers, compared with the targets established by the American Diabetes Association.     

Candidate gene association studies of the alpha 4 (CHRNA4) and beta 2 (CHRNB2) neuronal nicotinic acetylcholine receptor subunit genes in Alzheimer's disease

Consistent deficits in the cholinergic system are evident in Alzheimer's disease (AD) patients, including selective loss of alpha4beta2 nicotinic acetylcholine receptors in the brains of AD patients. Knockout mice for the beta2 subunit have impaired neuronal survival in ageing. Accordingly, we have analysed polymorphisms in the genes that encode the alpha4 and beta2 subunits, CHRNA4 and CHRNB2 respectively, for genetic associations with late-onset AD. A significant association for disease was observed for a non-coding polymorphism in CHRNB2 (odds ratio=0.57, 95% confidence interval=0.35-0.95, P=0.024). Replication analysis was performed in two further sample sets. While these did not individually yield significant results, a significant association remained when all samples were pooled (odds ratio=0.70, 95% confidence interval=0.52-0.95, P=0.019). These data suggest that this variant warrants further examination in large case-control series.     

Surrogate decision makers’ attitudes towards research decision making for critically ill patients

Purpose

To examine the attitudes and preferences of surrogate decision makers (SDMs) regarding their involvement in the consent to research process for ICU patients.

Methods

We presented 136 SDMs of critically ill patients in five ICUs with four hypothetical research scenarios: baseline interventional study of a placebo controlled RCT; study with higher risk of treatment complication; study comparing two accepted treatments; study with shorter enrolment window. For each we asked SDMs if they would want to be involved in the consent to research decision, and to rate the acceptability of their comfort with, and their sense of burden with their involvement. Participants were screened for symptoms of anxiety and depression using the Hospital Anxiety and Depression Scale.

Results

For the baseline scenario, most SDMs wished to be involved in research decision making (90?%; 95?% CI 84–95?%); responses varied little across study permutations. The majority considered their involvement to be acceptable (85?%; 95?% CI 77–90?%), whereas, a small minority rated it as being unacceptable (2?%; 95?% CI 1–6?%). Many were comfortable with being involved (50?%; 95?% CI 41–59?%), but the number decreased when risk of harm was higher (34?%; 95?% CI 26–43?%) or enrolment window was shorter (41?%; 95?% CI 33–50?%). A majority (62?%) reported symptoms of anxiety and many (38?%) had symptoms of depression.

Conclusion

Most of the interviewed SDMs wished to be involved in research decision making for critically ill and incapable loved ones. Variability existed, however, in their desire to be involved when decisions were time-sensitive or perceived risk was greater.     

Antibodies to diphtheria, tetanus and pertussis in infants before and after immunization with DTP (Triple Antigen) vaccine

Objective : To determine antibody levels to the Australian manufactured combined diphtheria, tetanus and pertussis (DTP) vaccine (Triple Antigen, CSL Ltd) in infante before and after their primary immunization course.
Methodology : Serosurvey (antibody prevalence study) in two groups: infants aged 5-9 weeks who had not received any immunizations ( n = 25), and infants aged 7-10 months who had received two ( n = 25) or three immunizations ( n = 57) with DTP, sampled from infants attending the Royal Children's Hospital, Melbourne, either as inpatients or outpatients between February and April 1993. The immunization history for each infant was determined from hospital records, the parent-held child health record, or the local council or family doctor who immunized the infant.
Results : Enzyme immunoassay (EIA) of antibodies to diphtheria and tetanus showed all infants to have adequate protective levels after two or three vaccinations (£0.01 IU/mL). All subjects who had received all three DTP vaccinations had detectable antibody to at least one pertussis antigen. Antibodies to the pertussis antigens filamentous haemagglutinin and pertussigen (pertussis toxin) were comparable to levels determined for whole cell pertussis vaccines used elsewhere in the world. EIA-determined antibodies to pertussis agglutinogen type 2 and agglutinogen type 3 showed substantially higher geometric mean titres when results for pre-immunization and post-immunization subjects were compared.
Conclusions : These data show that the Australian manufactured DTP vaccine has immunogenic properties similar to those of vaccines used elsewhere, and that antibody concentrations following immunization are at levels consistent with efficacy.     

Electron Spin Resonance Studies of Radiation Damage in Deoxyribonucleic Acid

Summary

Electron spin resonance (E.S.R.) spectroscopy has been used to make quantitative and qualitative measurements on irradiated deoxyribonucleic acid. Radical yields in six different samples are compared with those determined by other workers. The E.S.R. spectrum shows that the radiation produces at least two radical species, and the nature of one of these is discussed in detail.     

Shared learning in practice placements for health and social work students in East London: a feasibility study

A voluntary organisation providing family support and mental health services carried out an enquiry into the feasibility of setting up placements in primary care for students from professional qualifying courses in community nursing, social work and occupational therapy to experience shared practice learning in their placement. Consultation with a range of courses from two universities in London and with GP practices and other primary care agencies in East London established that there was wide support for the idea from practitioners, managers and academic teachers. It was recommended that a small number of pilot placements be set up. It was acknowledged that the diversity of placement requirements across the spectrum of professional education is a limiting factor in bringing students together for practice learning. The authors suggest that in the longer term, the development of an interprofessional approach to practice learning will require structural changes to professional courses so as to bring their placement requirements more into line with each other.     

Breadth of protection of the respiratory tract provided by different live-attenuated infectious bronchitis vaccines against challenge with infectious bronchitis viruses of heterologous serotypes

The regime of administering the infectious bronchitis (IB) Ma5 vaccine (Massachusetts serotype) at 1 day old and the heterologous 4/91 vaccine at 2 weeks of age, was shown to be highly effective in protecting the respiratory tract of specified pathogen free chickens. Protection, as measured by assessing ciliary activity of the tracheal epithelium following challenge, was excellent against challenge at 5 weeks of age with IB strains of many serotypes, isolated from disease outbreaks in different parts of the world. This vaccination protocol was more effective than revaccination with a vaccine of the same serotype as the first vaccine. Furthermore, significantly better protection was seen when the Ma5 vaccine was given before, rather than at the same time as or following, the 4/91 vaccine. It is suggested that the use of these two IB vaccines will frequently broaden the protection possible against challenge with IB isolates of many different serotypes, without the need to develop a new IB vaccine to combat each new IB serotype that emerges.     

Twice-daily budesonide inhalation suspension in infants and children < 4 and > or = 4 years of age with persistent asthma.

A retrospective analysis, based on a randomized, placebo-controlled, 12-week study in children 6 months to 8 years of age with persistent asthma, was performed to compare the efficacy and safety of budesonide inhalation suspension 0.25 mg and 0.5 mg twice daily vs. placebo in children < 4 and > or = 4 years of age. Both age groups demonstrated significant (p < or = 0.050) improvement in nighttime and daytime asthma symptom scores and decreased bronchodilator use compared with placebo. In addition, the safety profile of twice-daily budesonide inhalation suspension was favorable in both age groups.