Effects of albuterol and procaterol on exercise-induced asthma

Procaterol and albuterol, beta agonists, were studied using a placebo-controlled, repeated exercise challenge design in order to assess their duration of effectiveness in both bronchodilation and in modifying exercise-induced asthma (EIA). Fifty-three subjects aged 12 to 50 years who had at least a 20% drop in FEV1 during a screening exercise tolerance test were entered. Subjects took two inhalations of procaterol (10 micrograms/inhalation), albuterol (90 micrograms/inhalation), or placebo. Thirty minutes later they exercised on a treadmill at a workload sufficient to induce greater than or equal to 80% aerobic O2 consumption for six minutes. Pulmonary function was measured before and serially for 30 minutes after exercise. The same exercise challenge was repeated three, six, and nine hours after drug administration. Both procaterol and albuterol bronchodilated and modified EIA at 30 minutes and three hours, mean drops in FEV1 being 8.2 and 9.7% respectively at 30 minutes and 16.8 and 16.3% at three hours. This was compared with placebo falls of 30% and 26%. At six hours the subjects' response was similar after both procaterol and albuterol, and fewer subjects had a 20% fall in FEV1 than with placebo, although protection afforded by both beta agonists was substantially less than at three hours. Both drugs were tolerated well.     

High vs. low entrustment behaviors in the operating room

BackgroundOperative experience with an appropriate degree of supervised autonomy is critical to resident training. Progressively greater intraoperative entrustment has been associated with gradually higher levels of resident autonomy. This study attempts to identify consistently observed intraoperative behaviors that are linked with higher resident entrustment.MethodsThis qualitative study analyzed observational notes recorded by trained raters who provided entrustment scores for 204 surgical cases at Michigan Medicine from 2015 to 2017. Notes were coded in NVivo12. Thematic analysis was used to identify themes and patterns within the data.ResultsThe analysis generated 144 codes. Codes were clustered into 10 themes. These themes manifested differently in intraoperative behaviors strongly associated with high entrustment versus low entrustment.ConclusionThis study demonstrates key differences in intraoperative behaviors exhibited by residents and faculty in high and low entrustment interactions. Awareness of behaviors that enhance entrustment can help faculty augment resident learning and enable higher resident operative autonomy.     

Human acetylator genotype: Relationship to colorectal cancer incidence and arylamine N-acetyltransferase expression in colon cytosol

Polymorphic expression of arylamine N-acetyltransferase (EC 2.3.1.5) may be a differential risk factor in metabolic activation of arylamine carcinogens and susceptibility to cancers related to arylamine exposures. Human epidemiological studies suggest that rapid acetylator phenotype may be associated with higher incidences of colorectal cancer. We used restriction fragment length polymorphism analysis to determine acetylator genotypes of 44 subjects with colorectal cancer and 28 non-cancer subjects of similar ethnic background (i.e., approximately 25% Black and 75% White). The polymorphic N-acetyltransferase gene (NAT2) was amplified by the polymerase chain reaction from DNA templates derived from human colons of colorectal and non-cancer subjects. No significant differences inNAT2 allelic frequencies (i.e., WT, M1, M2, M3 alleles) or in acetylator genotypes were found between the colorectal cancer and non-cancer groups. No significant differences inNAT2 allelic frequencies were observed between Whites and Blacks or between males and females. Cytosolic preparations from the human colons were tested for expression of arylamine N-acetyltransferase activity. Although N-acetyltransferase activity was expressed for each of the arylamines tested (i.e., p-aminobenzoic acid, 4-aminobiphenyl, 2-aminofluorene, -naphthylamine), no correlation was observed between acetylator genotype and expression of human colon arylamine N-acetyltransferase activity. Similarly, no correlation was observed between subject age and expression of human colon arylamine N-acetyltransferase activity. These results suggest that arylamine N-acetyltransferase activity expressed in human colon is catalyzed predominantly by NAT1, an arylamine N-acetyltransferase that is not regulated byNAT2 acetylator genotype. The ability to determine acetylator genotype from DNA derived from human surgical samples should facilitate further epidemiological studies to assess the role of acetylator genotype in various cancers.     

Evidence that mechanisms dependent and independent of nitric oxide mediate endothelium-dependent relaxation to bradykinin in human small resistance-like coronary arteries

1. The effects of the nitric oxide (NO) synthase inhibitor, N^G-nitro-L-arginine (L-NOARG), the NO scavenger, oxyhaemoglobin (HbO) and high extracellular K⁺ upon endothelium-dependent relaxation to bradykinin were investigated in human isolated small coronary arteries.
2. Endothelium-dependent relaxations to bradykinin were compared in vessels contracted to ∼50% of their maximum contraction to 124 mM KCl Krebs solution, regardless of treatments, with the thromboxane A₂ mimetic, U46619 and acetylcholine. All relaxations were expressed as percentage reversal of the initial level of active force.
3. L-NOARG (100 μM) caused a small but significant, 12% (P<0.01), decrease in the maximum relaxation (R_max: 91.5±5.4%) to bradykinin but did not significantly affect the sensitivity (pEC₅₀: 8.08±0.17). Increasing the concentration of L-NOARG to 300 μM had no further effect on the pEC₅₀ or R_max to bradykinin. HbO (20 μM) and a combination of HbO (20 μM) and L-NOARG (100 μM) reduced R_max to bradykinin by 58% (P<0.05) and 54% (P<0.05), respectively. HbO (20 μM) and L-NOARG (100 μM, combined but not HbO (20 μM) alone, caused a significant 11 fold (P<0.05) decrease in sensitivitiy to bradykinin. HbO (20 μM) decreased the sensitivity to the endothelium-independent NO donor, S-nitroso-N-acetylpenicillamine (SNAP), approximately 17 fold (P<0.05).
4. Raising the extracellular concentration of K⁺ isotonically to 30 mM, reduced the R_max to bradykinin from 96.6±3.1% to 43.9±10.1% (P<0.01) with no significant change in sensitivity. A combination of HbO, L-NOARG and high K⁺ (30 mM) abolished the response to bradykinin. High K⁺ did not change either the sensitivity or maximum relaxation to SNAP.
5. In conclusion, L-NOARG does not completely inhibit endothelial cell NO synthesis in human isolated small coronary arteries. By comparison, HbO appeared to block all the effects of NO in this tissue and revealed that most of the relaxation to bradykinin was due to NO. The non-NO -dependent relaxation to bradykinin in the human isolated small coronary arteries appeared to be mediated by a K⁺-sensitive vasodilator mechanism, possibly endothelium-derived hyperpolarizing factor (EDHF).

     

RENAL TRANSPLANTATION – AN EARLY EXPERIENCE

Renal transplant (RT) is now a therapy of choice for end stage renal disease (ESRD). The Nephrology Unit, Asvini started functioning in Dec 90 and to date 1298 sittings of hemodialysis have been given to 45 patients. Of these, 35 were in ESRD and 11 patients underwent renal transplantation at this hospital during the period Jan 91 – Dec 93. One patient expired after 18 months of transplantation due to infection. Early experience in screening patients for RT, use of immunosuppression, management of rejection episodes and protocol are presented with special emphasis on its relevance to the Armed Forces.KEY WORDS: Transplantation, Renal Failure, Immunosuppression, Rejection     

SCREENING PROCEDURES IN PEDIATRICS

Pediatric health screening procedures, both prenatal and postnatal, have a tremendous potential in improving the health status of children and in turn reducing the resource burden on the parents and the State. The existing recommendations, inherent problems and different screening procedures are discussed. The need for suitable mass screening pediatric procedures in the Indian context is stressed.KEY WORDS: Pediatric screening procedures     

Family size, infections, and asthma prevalence in New Zealand children.

We conducted a prevalence case-control study to investigate the relation between family composition, infection, and development of asthma at age 7-9 years. Potential cases (399) and controls (398) were selected from the Wellington, NZ, arm of the International Study of Asthma and Allergies in Childhood, a population-based prevalence study. Further screening questions restricted cases to children with a diagnosis of asthma and current medication use (N = 233) and restricted controls to children without a history of wheezing and no diagnosis of asthma (N = 241). After controlling for confounders (including infections, atopy, and socioeconomic status), family size was strongly related to asthma. Having no siblings [prevalence odds ratio (POR) = 2.51; 95% confidence interval (CI) = 1.05-6.01] or one sibling (POR = 1.86; 95% CI = 1.14-3.03) was associated with an increased risk of asthma compared with having more than one sibling. Parent-reported rubeola infection (and possibly other similar viral exanthems) was independently associated with a decreased risk of asthma (POR = 0.48; 95% CI = 0.27-0.83), but reported pertussis infection (POR = 1.57; 95% CI = 0.58-4.24) and day care attendance in the first year of life (POR = 1.81; 95% CI = 0.93-3.51) were not strongly associated with increased risks of asthma.     

Assessment of abstracts submitted for the 1998 BNMS annual meeting: concordance or lottery?

The selection of abstracts for presentation at the Annual Meeting of the British Nuclear Medicine Society is an arduous task for the assessors. It is only to be expected that assessors' appreciation of an abstract will be biased by their interests and knowledge. This study assessed the concordance between the marks awarded by specialist and general assessors for the 173 abstracts submitted to the 1998 Spring BNMS meeting. The results showed considerable agreement among the markers for most comparisons. We conclude that the current combination of specialist assessors evaluating specific sections and three generalists assessing all abstracts appears to be working well.