Persistent improvement of type 2 diabetes in the Goto-Kakizaki rat model by expansion of the beta-cell mass during the prediabetic period with glucagon-like peptide-1 or exendin-4

In the Goto-Kakizaki (GK) rat, a genetic model of type 2 diabetes, the neonatal beta-cell mass deficit is considered to be the primary defect leading to basal hyperglycemia, which is detectable for the first time 3 weeks after birth. We investigated in GK females the short- and the long-term effects of a treatment with glucagon-like peptide-1 (GLP-1) or its long-acting analog exendin-4 (Ex-4) during the first postnatal week (during the prediabetic period). GK rats were treated with daily injections of glucagon-like peptide-1 (400 microg x kg(-1) x day(-1)) or Ex-4 (3 microg x kg(-1) x day(-1)) from day 2 to day 6 after birth and were evaluated against Wistar and untreated GK rats. Under these conditions, on day 7 both treatments enhanced pancreatic insulin content and total beta-cell mass by stimulating beta-cell neogenesis and regeneration. Follow-up of biological characteristics from day 7 to adult age (2 months) showed that such a GLP-1 or Ex-4 treatment exerted long-term favorable influences on beta-cell mass and glycemic control at adult age. As compared to untreated GK rats, 2-month-old treated rats exhibited significantly decreased basal plasma glucose. Their glucose-stimulated insulin secretion, in vivo after intravenous glucose load or in vitro using isolated perfused pancreas, was slightly improved. This contributed at least partly to improve the in vivo plasma glucose disappearance rate, which was found to be increased in both treated GK groups compared to the untreated GK group. These findings in the GK model indicated, for the first time, that GLP-1 or Ex-4 treatment limited to the prediabetic period delays the installation and limits the severity of type 2 diabetes. Under these conditions, GLP-1 represents a unique tool because of its beta-cell replenishing effect in spontaneously diabetic rodents. It may prove to be an invaluable agent for the prevention of human type 2 diabetes.     

Prognostic significance of wound infections following major head and neck cancer surgery: an open non-comparative prospective study

Objective We evaluated the incidence, risk factors and consequences of wound infection (WI) following major head and neck cancer surgery in an open non-comparative study.Patients and methods The study group, comprising 95 patients who underwent clean-contaminated procedures with opening of the upper aerodigestive tract for biopsy-proven squamous cell cancer, were studied over a 1-year period. Antibiotic prophylaxis was amoxicillin and clavulanic acid. More than 20 variables were prospectively recorded for each patient. The mean follow-up was 30 months.Main results The overall WI rate was 50.5% (48/95). Most pathogens isolated from samples were gram-negative rods. In univariate analysis, we found three risk factors for WI: alcohol consumption (P=0.07), a hypopharyngeal location (P=0.02) and laryngectomy stoma (P=0.01). WI were associated with postoperative fever (P=1.5×10^–11), postoperative antibiotic therapy (P=1.5×10^–5) and postoperative death (P=0.043). Patients without WI had a median postoperative hospital stay of 15 days compared with 29 days for those with WI (P<0.001). Healing of WI was achieved after a median time of 48 days. WI delayed postoperative radiation therapy in 21 out of 33 evaluable patients. But overall survival, and local and metastatic failures were similar with and without WI.Conclusions WI are associated with a heavy postoperative morbidity, but have no prognostic impact on cancer control.     

Psychosocial determinants of the intention of nurses and dietitians to recommend breastfeeding

OBJECTIVES: To identify the major psychosocial determinants of the intention of nurses and dietitians to recommend breastfeeding to new mothers for six months as well as the salient beliefs underlying this intention. METHOD: Following an open-ended questionnaire that sought to elicit their most significant beliefs, a standardized questionnaire based on a modified model of Ajzen's theory of planned behaviour, was sent to New Brunswick nurses and dietitians who graduated between January 1992 and December 1996. Multiple regression analysis determined which variables contributed the most to the prediction of intention. RESULTS: The main determinants of intention were perceived behavioural control and perceived professional norm. They explained 69% of the variance in intention. All salient beliefs underlying the perceived behavioural control were significantly associated with intention. CONCLUSION: To help nurses and dietitians to support and promote breastfeeding more effectively, programs should focus on changing perceived and true barriers to recommending breastfeeding, as well as the related perceived professional norm.     

Prevention of preparation errors of cytotoxic drugs in centralized units: from epidemiology to quality assurance

The centralized preparation of cytotoxic drugs is supposed to help preventing medication errors. Nevertheless, the residual risk of preparation errors has been demonstrated. Above all, prevention is based on the quality assurance policy. Following a previous work, this study valuates the effectiveness of a quality assurance policy and the impact of corrective actions. The study compares the rates of preparation errors observed before and after the corrective actions. The risk factors have also been studied. The study included 84,017 consecutive preparations. The results showed a significant reduction of overall (0.2% versus 0.4%) and major (0.1% versus 0.2%) errors between the two periods. This period impact has been validated by a multivariate analysis (OR were respectively 0.49 and 0.6, p < 10(-3)). The daily workload (> 60 preparations) appeared to be the most important risk factor (OR were respectively 2.4 and 3.2, p < or = 10(-3)). These results demonstrated the effectiveness of simple corrective actions. The follow-up on preparation errors appeared to be useful to raise technicians' awareness and to motivate them. An epidemiological approach allows to identify risk factors, and to definite relevant corrective actions.     

The relationship between sensory impairment and functional independence among elderly

Background  

It has been well established that increasing age is associated with decreasing functional ability in older adults. It is important to understand the specific factors that affect instrumental activities of daily living (IADL) and functional independence among older adults with sensory disabilities.     

Protection against acute lung injury by intravenous or intratracheal pretreatment with EPI-HNE-4, a new potent neutrophil elastase inhibitor

Excessive accumulation of active neutrophil elastase (NE) in pulmonary fluids and tissues of patients with cystic fibrosis (CF) is thought to act on the lungs, compromising their structure and function. The aim of this study was to investigate the in vitro and in vivo protective effect of a new, rapidly acting, potent (Ki = 5.45 x 10(-12) M and Kon = 8 x 10(6) M(-1) s(-1)) and specific human NE inhibitor, EPI-HNE-4, engineered from the Kunitz domain. The results demonstrated that this inhibitor was able to (i) effectively inhibit in vitro the high levels of active NE present in a medium as complex as sputum from children with CF, with a measured IC(50) equal or close to the calculated IC(50) in 60% of cases, and (ii) almost completely block (91%) the N-formyl-methionine-leucine-phenylalanine-induced migration of purified human neutrophils across a Matrigel basement membrane. Intratracheal administration (250, 175, or 100 microg per rat) of the inhibitor 5 min before instillation of pure human NE (HNE) (150 microg per rat) to rats induced effective, dose-dependent protection of the lungs, 4 h later, from hemorrhage, serum albumin leakage, residual active NE, and discrete neutrophil influx in air spaces induced by instillation of pure HNE. Intravenous administration (3 mg per rat) of EPI-HNE-4, 15 min before instillation of the soluble fraction of pooled sputum (delivering 120 microg of active NE per rat) from children with CF, effectively reduced (64%), 4 h later, the massive neutrophil influx induced by sputum instillation. Overall, these data strongly suggest that associated aerosol and systemic administration of EPI-HNE-4 would be beneficial in the treatment of CF.