Delayed and persistent suppression of bronchoconstriction by trypsin in the airway lumen.

Mucosal trypsin, a protease-activated receptor (PAR) stimulant, may have an endogenous bronchoprotective role on airway smooth muscle. To test this possibility the effects of lumenal trypsin on airway tone in segments of pig bronchus were tested. Bronchial segments from pigs were mounted in an organ chamber containing Kreb's solution. Contractions were assessed from isovolumetric lumen pressure induced by acetylcholine (ACh) or carbachol added to the adventitia. Trypsin, added to the airway lumen (300 microg x mL(-1)), had no immediate effect on smooth muscle tone but suppressed ACh-induced contractions after 60 min, for at least 3 h. Synthetic activating peptides (AP) for PAR1, PAR2 or PAR3 were without effect, but PAR4 AP caused rapid, weak suppression of contractions. Lumenal thrombin was without effect and did not prevent the effects of trypsin. Effects of trypsin were reduced by N(omega)-nitro-L-arginine methyl ester but not indomethacin. Trypsin, thrombin and PAR4 AP released prostaglandin E2. Adventitially, trypsin, thrombin and PAR4 AP (but not PAR2 AP) relaxed carbachol-toned airways after <3 min. The findings of this study show that trypsin causes delayed and persistent bronchoprotection by interacting with airway cells accessible from the lumen. The signalling mechanism may involve nitric oxide synthase but not prostanoids or protease-activated receptors.     

Angiotensin Converting Enzyme Inhibitors: Animal Experiments Suggest a New Pharmacological Treatment for Alcohol Abuse in Humans

The prevalence of heavy alcohol consumption is a major problem of increasing proportions throughout the world. Although alcohol sensitizing drugs and more recently serotonin uptake inhibitors are drug interventions with some following, their long term beneficial consequences have yet to be demonstrated. In recent years, we have demonstrated that manipulating activity in the renin-angiotensin system will dramatically alter voluntary alcohol consumption in rats. Based on these findings, the present study evaluated the ability of a class of drugs known as the angiotensin converting enzyme inhibitors to reduce voluntary alcohol drinking in laboratory animals. These drugs prevent the conversion of angiotensin I to angiotensin II. They have been licensed for use in Europe and North America and are indicated in the treatment of hypertension. Our experiments showed that both captopril (Capoten, Squibb) and enalapril (Vasotec, Merck Sharpe & Dohme) can reduce alcohol drinking in both normotensive and hypertensive animals regardless of whether the pattern of intake is in a bout or of a less exaggerated nature. Furthermore, this change in alcohol intake can occur without concomitant changes in blood pressure, plasma renin activity, overall fluid balance, or the distribution and metabolism of alcohol. Taken together these findings suggest that the angiotensin converting enzyme inhibitors should be evaluated in a clinical setting for they may prove to be a useful new treatment or treatment adjunct for alcohol abuse in humans.     

Advances in pharmacotherapy: depression in the elderly– issues and advances in treatment

Depression continues to be a major cause of morbidity and mortality in the elderly. It is estimated that 1–5% of elderly persons who live in the community and 5–43% of nursing–home patients have major depression. Symptoms of depression in the elderly do not differ substantially from younger patients. Tricyclic antidepressants continue to be the drugs of choice in the elderly because of their long record of use with proven efficacy, known adverse effect profile and availability of less expensive generic formulations. The newer secondgeneration antidepressants, including serotonin reuptake inhibitors, appear to offer a major advantage of fewer serious adverse effects in the elderly. This review will highlight recent developments regarding the prevalence and treatment of depression in the elderly.     

The effect of psychosocial factors on lung cancer mortality at one year

In this study newly diagnosed male and female lung cancer patients admitted to two Ontario Cancer Foundation treatment clinics were interviewed. Information was obtained on demographic variables, presence of other chronic illness and the following psychosocial attributes: locus of control, social support and personality traits. From the clinic charts, information on stage of disease and pathological diagnosis was obtained. After controlling for the effects of stage and pathological diagnosis, the following psychological variables were found to increase the odds of death from lung cancer among males and females combined at one year after diagnosis: a high need for one aspect of social support, a reserved personality and the extremes of the personality trait soberness vs enthusiasm.     

Regulation of alcohol consumption by the renin-angiotensin system: a review of recent findings and a possible mechanism of action.

The renin-angiotensin system has traditionally been associated with the regulation of fluid and electrolyte balance. In this review we summarize the data which ascribes a completely new function to this system, i.e., the regulation of alcohol consumption. In addition, we suggest a possible mechanism for this effect based on the concept of a satiety or stop process. The approach taken was to examine the effect on alcohol intake of a wide variety of drug, genetic, dietary, surgical and neurosurgical manipulations, each of which has a range of biological effects characteristic of that manipulation, but all of which share the common property of altering activity in the renin-angiotensin system. The effect of these manipulations on alcohol intake was most parsimoniously explained by reference to their ability to raise or lower activity in the renin-angiotensin system. Any intervention which modulates activity in this system, either directly or indirectly, is likely to have consequences for alcohol consumption.     

Hearing loss and otitis media on Guam: impact of professional services

In less than two decades, there has been a dramatic reduction in the prevalence of otitis media and perforations among Guam's school-aged children. In addition, hearing loss due to chronic middle ear disease as a cause of disqualification from military service has dropped from a first rank order cause to next-to-last. However, there has been no reduction in the prevalence of otitis media in the preschool population. The reduction in chronic ear disease is the result of improved access to primary care, intensive hearing screening, wide availability of audiologic diagnostic and follow-up services, and comprehensive otologic care. It is essential that these services continue to be available to Guam's children to avoid a reversal of these dramatic gains. Attention must now focus on how to achieve similar gains for Micronesian children who remain restricted in their access to these resources.     

Intra-arterial thrombolysis for acute limb ischemia: a three-year experience

Peripheral arterial thromboembolism and thrombosis of arterial grafts continue to threaten viability of extremities. Percutaneous intra-arterial thrombolysis (IAT) and angiodilatation have afforded limb salvage in some of these patients. Proper patient selection appears to be the hallmark of success with IAT. During a recent three-year period, we used IAT in 32 extremities in 28 patients who had acute arterial insufficiency. Before IAT, 16 extremities were painful at rest, and 16 had incapacitating claudication. The overall success rate was 38%, but some degree of thrombolysis occurred in 88%. Limb salvage was achieved in 27 of 32 extremities (84%). Only five of 17 limbs (29%) with arterial graft thrombosis required no operation or an operation of lesser magnitude than predicted before IAT. Of six extremities with native arterial embolism, four (67%) were completely cleared with IAT. Major complications occurred in eight cases (25%), with two IAT-related deaths (6%). This study suggests that IAT is best reserved for individuals with acute limb ischemia caused by arterial embolus, those whose degree of ischemia would tolerate a 24-hour trial of IAT, and those whose femoral or tibial runoff is not likely to require remedial operation.     

Broadening the reach of cardiac rehabilitation to rural and remote Australia.

BACKGROUND: Cardiac rehabilitation (CR) has an evidence base but traditional models may not readily apply to people living in rural and remote regions. AIM:: To outline published comprehensive and non-hospital based CR models used for people discharged from hospital after a cardiac event that have potential relevance to those living in rural and remote areas in Australia. METHODS: The PubMed database was searched using Medical subject headings (MeSH) terms and the key word 'cardiac rehabilitation' limited to clinical trials. Articles were retrieved if they included at least two components of CR and were not based in an outpatient setting. RESULTS: No CR models specifically developed for rural and remote areas were identified. However, 14 studies were found that outlined 11 non-conventional comprehensive CR models. All provided CR in a home-based setting. Health professionals provided support via telephone contact or home visits, and via resources such as the Heart Manual. Reported outcomes from these CR programs varied: ranging from an increase in knowledge of risk factors, to improvements in physical activity, decreased risk factor profile, improved psychological and social functioning and reductions in health service costs and mortality. CONCLUSION: Home-based, CR models have the most substantive evidence base and, therefore the greatest potential to be developed and made accessible to eligible people living in rural and remote areas.     

T cell subsets in human colostrum

Lymphocytes from 10 paired colostrum and peripheral blood specimens were examined to determine if the colostral T cell population differs from the peripheral blood T cell population in subset distribution. The percentages of lymphocytes staining with OKT3, OKT4, and OKT8 murine monoclonal antibody were determined. Lymphocytes from colostrum were 74.7 +/- 2.5% OKT3+, 50.6 +/- 2.3% OKT4+, 24.0 +/- 1.7% OKT8+, whereas peripheral blood lymphocytes were 78.7 +/- 1.9% OKT3+, 48.4 +/- 1.4% OKT4+, and 29.8 +/- 1.6% OKT8+. The percentage of colostrum lymphocytes positive for OKT3 was significantly although not strikingly lower than the OKT3 percentage for blood lymphocytes (p less than 0.05). This difference was due to the lower percentage of OKT8 positive lymphocytes in colostrum compared with blood (p less than 0.01). Although the T cell subset distribution of colostrum generally appears to be similar to that in the peripheral blood, there were small differences in OKT3 and OKT8 percentages that were statistically significant suggesting the possibility of some selectivity of the colostral T cell population.