Modulation of immune response with ornithine A-ketoglutarate in burn injury: an arginine or glutamine dependency?

Enterally administered ornithine alpha-ketoglutarate (OKG) is an efficient complement of nutritional support in trauma situations, especially after burn injury. A typical feature observed in this intense catabolic state is insufficient production of glutamine (Gln) and arginine (Arg), two amino acids (AAs) involved in the immune response. As OKG in vivo metabolism generates these two AAs, we investigated, in burned rats, the action of OKG with regard to modulation of immunity. Male Wistar rats were randomly allocated to four groups. On day 0, 12 rats were burned with boiling water (20% body surface area). After a 24-h fast, they were enterally refed for 48 h using Osmolite, as a low-calorie low-nitrogen regimen, supplemented with either 5 g OKG x kg(-1) x d(-1) (n = 6) or an equivalent amount of nitrogen in the form of glycine (n = 6). Non-burned pair-fed controls treated with glycine (n = 6) and healthy rats fed ad libitum (n = 6) were also studied. Nitrogen balance was assessed from daily measurement of total nitrogen excretion. On day 3, thymus, Anterior tibialis muscle and proximal jejunum weights were recorded. Muscle and intestinal AA concentrations were also quantified. OKG counteracted (P<0.01) the thymic involution that occurs with burn injury, and increased the concentrations of Gln and Arg in both the muscle (P<0.01 and P<0.05, respectively) and the jejunum (P<0.01 for Gln). When all groups were taken together, a positive correlation was found between thymus weight, and Gln and Arg muscle concentrations (r = 0.71, P<0.001 and r = 0.58, P<0.01, respectively). Furthermore, as expected, OKG improved nitrogen balance. As it is known that total number of thymocytes parallels thymic weight, and as Gln and Arg are essential nutrients for activated immune cells, our results suggest that Gln and Arg derived from OKG are responsible for the immunomodulating properties of this molecule in burn injury.     

Testing various methods of introducing health charts into medical records in family medicine units.

OBJECTIVE: To test three methods of introducing health charts into the medical records of six family medicine units. DESIGN: Quasi-experiment. PARTICIPANTS: The staff physicians and family medicine residents in all six units and the nurses in two units. INTERVENTIONS: Group 1 (minimal intervention): health charts, a user's guide and one training session. Group 2 (intermediate intervention): same intervention as for group 1 plus two feedback sessions at 3 and 6 months. Group 3 (maximum intervention): same intervention as for group 2 plus promotion of the team concept (nurses were included). The intervention phase lasted from September 1987 to August 1988. OUTCOME MEASURES: The frequency with which the health charts were used, the item scores of each preventive care activity and the overall unit scores. Data were gathered through chart audits at baseline and at the end of the intervention phase. RESULTS: The frequency with which the health charts were used varied from 3.9% to 26.9%. The greatest increases in item scores were observed in the use of mammography (20.0%), counselling on lifestyle (19.4%) and breast examination (17.2%). Although the overall improvement in the unit scores was statistically significant (p less than 0.05) the hypothesis of an increasing gradient of effect across the three intervention groups could not be tested because of the variation in scores across the units. CONCLUSION: Health charts and other similar tools are useful; however, they are not sufficient to change practice behaviours. The support of a "champion" on the health care team might well be a determining factor of success for the delivery of preventive services in primary care practice.     

Thiopurine S-methyltransferase gene polymorphism is predictive of azathioprine-induced myelosuppression in heart transplant recipients

Azathioprine (AZA) is metabolized via the cytosolic enzyme thiopurine S-methyltransferase (TPMT). TPMT activity exhibits genetic polymorphism with four prevalent (75%) mutant alleles TPMT*2 (G238C) and TPMT*3 (A719G and/or G460A) and a wild-type allele TPMT*1. To test the hypothesis that presence of these mutations is associated with greater toxicity of AZA in heart transplant recipients, 30 consecutive patients treated with AZA were followed up for the first month after heart transplant. Mutation of TPMT gene (mutation-specific polymerase chain reaction-based methods) was observed in four patients (A719G: n = 2; A719G plus G460: n = 2). Agranulocytosis did not occur in patients with the wild genotype. It occurred in the two patients with mutation A719G and there was a 40% drop in neutrophils in the two other patients. Discontinuation of AZA in the four mutant patients corrected for the drop. Presence of TPMT mutations is associated with a greater likelihood of agranulocytosis. Determination of these mutations could reduce the risk for hematological side-effects.     

Nosocomial respiratory syncytial virus infection in Canadian pediatric hospitals: a Pediatric Investigators Collaborative Network on Infections in Canada Study

OBJECTIVE: To determine nosocomial transmission of respiratory syncytial virus (RSV) in Canadian pediatric hospitals, outcomes associated with nosocomial disease, and infection control practices. DESIGN: A prospective cohort study in the 1992 to 1994 winter respiratory seasons. SETTING: Nine Canadian pediatric university-affiliated hospitals. PARTICIPANTS: Hospitalized children with symptoms of lower respiratory tract infection (at least one of cough, wheezing, dyspnea, tachypnea, and apnea) and RSV antigen identified in a nasopharyngeal aspirate. RESULTS: Of 1516 children, 91 (6%) had nosocomial RSV (NRSV), defined as symptoms of lower respiratory tract infection and RSV antigen beginning >72 hours after admission. The nosocomial ratio (NRSV/[com-munity-acquired RSV {CARSV})] + NRSV) varied by site from 2.8% to 13%. The median length of stay attributable to RSV for community-acquired illness was 5 days, but 10 days for nosocomial illness. Four children with NRSV (4. 4%) died within 2 weeks of infection, compared with 6 (0.42%) with CARSV (relative risk = 10.4, 95% confidence interval: 3.0, 36.4). All sites isolated RSV-positive patients in single rooms or cohorted them. In a multivariate model, no particular isolation policy was associated with decreased nosocomial ratio, but gowning to enter the room was associated with increased risk of RSV transmission (incidence rate ratio 2.81; confidence interval: 1.65, 4.77). CONCLUSIONS: RSV transmission risk in Canadian pediatric hospitals is generally low. Although use of barrier methods varies, all sites cohort or isolate RSV-positive patients in single rooms. Children with risk factors for severe disease who acquire infection nosocomially have prolonged stays and excess mortality.     

Familiar Face and Voice Matching and Recognition in Children with Autism

Relatively able children with autism were compared with age- and language-matched controls on assessments of (1) familiar voice-face identity matching, (2) familiar face recognition, and (3) familiar voice recognition. The faces and voices of individuals at the children's schools were used as stimuli. The experimental group were impaired relative to the controls on all three tasks. Face recognition and voice recognition correlated significantly with voice-face identity matching, but not with each other, suggesting that the recognition impairments jointly cause the matching impairment. Neither chronological age nor verbal mental age were consistently related to the recognition and matching impairments.