Protection against aspirin-induced human gastric mucosal injury by bosentan, a new endothelin-1 receptor antagonist

BACKGROUND: Gastric ulceration induced by aspirin and by non-steroidal anti-inflammatory drugs (NSAIDs) is a major clinical problem. The mechanism of injury is unclear. There is evidence that NSAID-induced injury may cause endothelin activation. Endothelin-induced vasoconstriction has been shown to be capable of causing gastric ulceration. AIM: To investigate whether acute gastroduodenal injury induced in humans by aspirin can be prevented by the endothelin-1 antagonist, bosentan. METHODS: Eighteen healthy volunteers each received 5 x 900 mg aspirin every 12 h on three separate occasions (with either placebo, bosentan 700 mg or misoprostol 400 mg). Treatment order was randomized by Latin square design. Subjects were endoscoped and erosions counted before and 90 min after the first and last dose of aspirin. Plasma concentrations of bosentan were measured up to 5 h post-dose. RESULTS: There was a significant reduction in the mean number of erosions in the aspirin plus bosentan and aspirin plus misoprostol groups after the first dose of aspirin, compared with controls (aspirin plus placebo) (P<0.05). This was not sustained after the fifth dose of aspirin in the aspirin plus placebo and aspirin plus bosentan groups, but was still present in the aspirin plus misoprostol group. The mean plasma concentration of bosentan measured 3.5 h post-dose fell from 4510 (95% CI: 2791-6230) ng/mL after the 1st dose to 2508 (95% CI: 1733-3283) ng/mL after the 5th dose (P = 0.02). CONCLUSION: Endothelin receptor antagonism by bosentan can protect the gastric mucosa against aspirin damage. After five doses, bosentan levels fell, possibly because of enzyme induction, and protection was no longer evident. Further investigation is needed to assess whether higher doses would be effective.     

Abnormalities in surfactant in sudden infant death syndrome as a postmortem marker and possible test of risk

To determine whether physical abnormalities in lung surfactant, particularly inversion of the hysteresis between surface tension and surface area, are an effective postmortem marker for sudden infant death syndrome (SIDS).

Methodology:

Bronchoalveolar lavage (BAL) was employed to obtain lung rinsings from 55 infants under 24 months of age at autopsy, comprising 34 index cases and 21 controls. Folch reagent was used to extract the lipoid content which was then applied at two surface concentrations, fixed and BAL-determined (BALD), to the pool of a Langmuir trough in which surface tension (γ) was measured continuously by the Wilhelmy method as surface area ( A ) was cycled.

Results:

The γ: A loops from SIDS samples were inverted relative to controls (i.e. they were hysteresis reversed, this inversion being quantified by an empirical surface tension:area reversal (STAR) score). There was a wide scatter of STAR scores, but a critical value was found which offered a significant ( P = 0.017) separation of SIDS cases from controls for a fixed surface concentration and a highly significant separation ( P = 1.0 × 10^-4) for BALD surface concentrations. Differences in the yields of phospholipid and proteolipid, or their correlation to STAR scores, did not reach statistical significance.

Conclusions:

Inversion of the γ: A loops (i.e. hysteresis inversion) would appear to offer a better postmortem marker of SIDS than any reported previously, the procedure having potential for development as a prospective test indicating the risk of this disease.     

CROSS SECTIONAL ANALYTIC STUDY OF AWARENESS REGARDING FACTORS RELATED TO CHILD SURVIVAL AMONG MARRIED WOMEN IN A SEMI-URBAN COMMUNITY

A cross sectional analytic study was undertaken on 480 married women living in a semi-urban locality in Pune, with the objective of assessing their awareness regarding factors related to child survival. It was observed that 62.1 per cent of the ladies had adequate knowledge about immunisation. A highly significant trend was evident as regards knowledge about immunisation and formal education and socio-economic status (p<0.01). 93 per cent ladies initiated breast feeding within 24 hours of birth of the new born. Significantly larger proportion of ladies from lower education favoured prolonged breast feeding (p<0.001) and favoured late introduction of top milk (p<0.001). In general, the awareness about growth chart was very poor with only 3.5 per cent ladies having adequate knowledge. Larger family size was significantly associated with declining probability of use of oral rehydration solution (ORS). Certain recommendations for improving the awareness regarding child survival have been submitted accordingly.KEYWORDS: Child survival, Health awareness     

Change in obesity‐related metabolic abnormalities associated with body mass index improvement through life‐style intervention: A meta‐regression

The reduction in body mass index standard deviation score (BMI‐SDS) associated with improvement in biomarkers relating to metabolic health in obese children is unknown. We aimed to establish the change in BMI‐SDS associated with improved inflammation, liver function, and insulin resistance to inform clinical guidelines for pediatric weight management interventions and to assess the efficacy of future trials. A large‐scale systematic review was conducted to identify relevant studies. Studies of children with a diagnosis of obesity according to defined BMI thresholds, participating in lifestyle interventions to reduce obesity, were included. Studies must have reported baseline (pre‐) and postintervention (or change of) BMI‐SDS and either fasting glucose, homeostatic model of insulin resistance (HOMA‐IR), alanine aminotransferase (ALT), C‐reactive protein (CRP), or interleukin‐6 (IL‐6). A series of meta‐regressions were conducted to establish links between BMI‐SDS change scores and change in metabolic markers of health. Sixty‐eight articles were identified. From the meta‐regression analyses, across all study subsets, greater mean falls in all four parameters, (HOMA‐IR, Glucose, ALT, and CRP) were observed with greater mean loss of BMI‐SDS, but the trends were only statistically significant for HOMA‐IR and CRP (P = .003; P = .021). However, we could not find minimum changes in BMI‐SDS that would ensure a fall in these outcomes. At this time, we are unable to recommend a definitive value of BMI‐SDS reduction needed to improve the markers of metabolic health. Future trials should aim to report additional indices of derived BMI values, which may better reflect changes in actual adiposity.     

Long-Term Performance of Endocardial Leads with Steroid-Eluting Electrodes

During a three-year period, 48 steroid-eluting leads (Medtronic* 4003 and 4503] have been implanted in 39 patients. 23 were implanted in the atrium and 25 in the ventricle. 36 patients with 45 leads have been observed for more than 12 months. Stimulation thresholds have been followed using pulse generators with variable output (vario): 12 atrial and 11 ventricular leads, 4 atrial leads and 11 ventricular leads have been followed using pulse generators with variable pulse-width (auto-threshold], P-waves have been followed using telemetry or sensitivity programming (23 atrial leads). R-waves have been followed using telemetry in 11 ventricular leads. Mean stimulation thresholds after 2 years are 0.7 V ± 0.2 in the atrium and 0.8 V ± 0.3 in the ventricle. P-waves after 2 years are of magnitudes allowing a sensitivity setting of 2.5 mV in 12 cases and of 1.5 mV in 2 cases; R-waves have in all cases been high enough to permit lowest programmable sensitivity setting. During the observation time, two patients have died from nonpacing-related causes. The results obtained from this investigation document low stimulation thresholds and good sensing levels in both ventricle and atrium using the steroid-eluting electrode with no significant changes after 6 weeks postimplant.     

Reduction of body doses in rotational panoramic radiography by means of reduced beam width in combination with rare earth intensifying screens

Abstract – The absorbed doses in the body of a Rando-Alderson phantom were measured in rotational panoramic radiography (OP-5) with LiF-700 crystals using conventional intensifying screens and standard collimator, as well as rare earth intensifying screens and a collimator slit of reduced width. The reduction of the absorbed doses obtained by using the latter combination was calculated. The reduction range in different regions was 0–50%. The greatest reduction was obtained in the cranial part of the phantom. In the caudal part little or no reduction was observed, probably because leakage radiation contributes substantially to the absorbed doses in this area. The average dose equivalent was calculated for organs in which measurements were made in several locations. The reduction was about 50% for these organs except for the gonads (8%). Compared to the estimated average annual dose equivalent originating from the natural background radiation sources, the dose equivalent resulting from this X-ray examination was very small except in the thyroid gland. In this organ the dose equivalent from one exposure corresponded to 36 days of natural background radiation, but it could be reduced to 18 days by using rare earth intensifying screens in combination with reduced beam width.     

Pharmacokinetic profile of controlled release ketoprofen in elderly patients.

The pharmacokinetics of ketoprofen following the administration of the first and final dose of a controlled release formulation (200 mg ketoprofen) once daily for 10 days to nine elderly patients have been studied. Plasma ketoprofen concentrations were measured by h.p.l.c. The data were compared to previously reported studies in young male volunteers. Mean +/- s.d. peak plasma concentrations (5.6 +/- 1.75 micrograms ml-1 and 6.3 +/- 2.7 micrograms ml-1 on day 1 and day 10, respectively) were higher than those reported in young volunteers given similar treatment, but similar to those reported in young volunteers following 50 mg four times daily of conventionally formulated ketoprofen, and markedly lower than reported following a single 100 mg dose of ketoprofen. The half-life for drug release (mean +/- s.d.) from the controlled release formulation (8.5 +/- 7.4 h) and accumulation upon repeated dosing (28%) were essentially the same as reported for young volunteers. The area under the plasma concentration-time curve was about 65% greater than reported in young volunteers following administration of controlled release ketoprofen. This increase in exposure to ketoprofen is probably partly due to the lower volume of distribution in the elderly and partly due to a reduced renal excretion of the glucuronide metabolite of ketoprofen. It was concluded that controlled release ketoprofen may be administered in standard doses (200 mg once daily) to elderly patients whose elimination processes are not severely impaired (i.e. severe renal failure or hepatic disease).(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevention of Infusion Thrombophlebitis

Thrombophlebitis is a frequent and discomforting complication following infusions into peripheral veins. In controlled clinical and animal experiments, it has also been shown that following factors reduce the risk of development of infusion thrombophlebitis: a short infusion time, neutralization of the acid glucose solutions, addition of heparine to sugar solutions, use of short and thin needles instead of plastic cannulae or 30 cmteflon catheters, use of 5% glucose instead of more concentrated solutions and use of glucose in preference to fructose. The importance of in-line membrane filters is not convincing, and the addition of hydrocortisone and the effects of changing administration sets seem without clinical importance. In conclusion, it is possible in clinical praxis to follow principles, which minimize the risk of the unpleasant and long-lasting complication - infusion thrombophlebitis.