Prevalence of hypoglycemia during oral glucose tolerance testing in adults with cystic fibrosis and risk of developing cystic fibrosis-related diabetes

Background

Hypoglycemia in cystic fibrosis (CF) patients during the oral glucose tolerance test (OGTT) has been reported; however, these patients have not been well-characterized. Few studies have examined whether hypoglycemia during the OGTT increases the risk of developing CF-related diabetes (CFRD). Objectives of this study were to describe the characteristics of CF patients with hypoglycemia during the OGTT and to determine the incidence and time to development of CFRD in those with hypoglycemia.

Platelet-derived growth factor in vivo: levels, activity, and rate of clearance

Platelet-derived growth factor (PDGF) is a potent mitogen for many cultured connective tissue cells. It is present in concentrated form within the platelet alpha-granules and is believed to be released during platelet degranulation at sites of vascular injury. We have used a sensitive radioreceptor assay to measure PDGF levels in whole blood serum from normal humans [17.5 +/- 3.1 (SD) ng/mL] and baboons (2.7 +/- 1.2 ng/mL). PDGF was not detected in plasma from either species. In addition, plasma was found to substantially reduce the ability of added purified PDGF to bind to the cell surface PDGF receptor on cultured cells, suggesting that plasma may contain a PDGF-binding protein that would serve to inactivate PDGF released into plasma. Calculations of PDGF concentrations in serum have been corrected for the effects of the binding protein. 125I-PDGF injected intravenously into normal baboons was cleared rapidly from the plasma (t1/2 = two minutes). The rapid clearance of 125I-PDGF did not result from iodination damage, as purified unlabeled PDGF was cleared with comparable kinetics. The rapid clearance of purified and iodinated PDGF did not result from changes in PDGF structure during purification or from removal of PDGF-associated proteins during purification, as PDGF present in freeze-thaw lysates of fresh platelets was cleared equally rapidly. We conclude that release of PDGF at sites of vascular injury would greatly increase the local concentration of PDGF and that PDGF not localized to the site of injury would be rapidly cleared from the circulation.     

Depressant effects of fast sodium channel blockade on the electrical activity of ischaemic canine ventricle: mediation by the sympathetic nervous system

In this study we examined the possibility that local anaesthetic agents such as tetrodotoxin may exacerbate electrical changes during acute myocardial ischaemia by inhibiting fast sodium channels, both in cardiac cells and in sympathetic nerve terminals. Bipolar electrograms were recorded during serial 2 to 5 min occlusions of the left anterior descending coronary artery in open-chest, anaesthetised dogs. Tetrodotoxin (1 or 2 micrograms X kg-1 iv) given prior to occlusion did not affect activation times or electrograms in normal myocardium but exacerbated activation delay and loss of electrogram amplitude during ischaemia. Bilateral stellectomy reversed the effects of tetrodotoxin during ischaemia. Tetrodotoxin (1 microgram X kg-1 iv) reduced changes in heart rate and mean arterial blood pressure produced by stellate ganglia stimulation. Intracoronary infusion of tetrodotoxin (10(-5) mol X litre-1) during normal perfusion lengthened mean effective ventricular refractory periods and propranolol (0.5 mg X kg-1 iv) or bilateral stellectomy prevented this effect. Thus, tetrodotoxin appeared to increase ventricular refractoriness and exacerbate ischaemia-induced activation delay by inhibiting sympathetic nerve activity. Other agents with local anaesthetic properties may have similar effects.     

Human papillomavirus and oral disease – emerging evidence: a review

Human papillomavirus (HPV) infections have received considerable attention in recent years. Of the 120 or so known types of the virus, some cause a variety of benign wart‐like lesions of the skin and genital and oral mucosae, whilst others are aetiologically associated with cervical and anogenital cancers. Recent epidemiologic evidence suggests that HPV may also be an independent risk factor for oropharyngeal cancer. In this context it has been suggested that HPV virus may modulate the process of carcinogenesis in some tobacco and alcohol induced oropharyngeal cancers and act as the primary oncogenic agent for inducing carcinogenesis among non‐smokers. Dental practitioners have a major role in detecting all lesions of the oral mucosa caused, or possibly caused, by HPV. This paper briefly reviews the current state of knowledge of molecular and clinical aspects of HPV infections of the oral mucosa.     

Multi-centre research surveillance project to reduce infections/phlebitis associated with peripheral vascular catheters

A surveillance project was undertaken on 37 surgical wards by infection control nurses with the aim of reducing phlebitis/infections associated with peripheral vascular catheters, and to identify risk factors. Data on 2934 catheters in situ longer than 24h was collected in two separate surveillance periods and results were fed back after each surveillance period. Four significant risk factors were identified; what the catheters were used for, the duration the catheters were in situ, the surveillance period (the first surveillance period had a higher phlebitis rate than the second) and whether an infusion pump was used. Logistic regression analysis showed that each of these had a significant effect after adjusting for the effects of the other three factors.     

The growth of breast fed and artificially fed infants from birth to twelve months

Growth data collected from 394 healthy infants were analysed in relation to feeding practices. Infants were grouped on the basis of sex, if breast fed or artificially fed, and duration of breast feeding. From birth to 3 months, weight gains were similar for boys (2.5 kg) and also for girls (2.3 kg) irrespective of feeding method. From 3 to 6 months weight gains were greater in infants who were artificially fed from birth (2.0 kg both sexes) or breast fed for only a short time (1.9 kg) than for those exclusively breast fed for 6 months (1.6 kg) or longer (1.7 kg). Weight gains continued to be greater in artificially fed infants after 6 months. Over 12 months, artificially fed boys gained 410 g and girls 750 g more than those who were breast fed from birth. These differences occurred even though the artificial feedings that prevailed to 6 months and longer were low-solute ('humanized') formulas.     

A population based study of the impact of corticosteroid therapy and delayed diagnosis on the outcome of childhood pneumococcal meningitis.

BACKGROUND: Despite an extensive literature, the impact of both adjunctive steroid therapy and delayed diagnosis on the outcome of childhood pneumococcal meningitis is controversial. AIM: To determine the independent contribution of corticosteroid therapy and delayed diagnosis on the outcome of childhood pneumococcal meningitis in a representative population with good access to medical services. METHODS: Data were obtained from laboratories and hospital records to assemble a population register in Sydney, Australia, 1994-99. Follow up questionnaires were completed by attending physicians. RESULTS: A total of 122 cases of pneumococcal meningitis aged 0-14 years were identified. Almost 50% of 120 children with available records either died (n = 15) or had permanent neurological impairment (n = 39). Early use (before or with parenteral antibiotics) of corticosteroids protected against death or severe morbidity (adjusted OR 0.21, 95% CI 0.05 to 0.77). Delayed diagnosis was associated with increased morbidity in survivors (OR 3.4, 95% CI 1.03 to 11.4) but not with increased mortality. CONCLUSION: In a population with good access to health care and after adjusting for other known prognostic variables, early recognition of pneumococcal meningitis and treatment with adjunctive dexamethasone significantly improves outcomes. These data add to those from randomised controlled trials. Implementation requires development of protocols and guidelines for use in emergency departments.     

Identification of the key amino acids of gliai cell line-derived neurotrophic factor family receptor alpha 1 involved in its biological function

Glial cell line-derived neurotrophic factor （GDNF） plays a critical role in neurodevelopment and survival of midbrain dopaminergic and spinal motor neurons in vitro and in vivo. The biological actions of GDNF are mediated by a two-receptor complex consisting of a glycosylphosphatidylinositol-linked cell surface molecule, the GDNF family receptor alpha 1 （GFR alpha 1）, and receptor protein tyrosine kinase Ret. Although structural analysis of GDNF has been extensively examined, less is known about the structural basis of GFR alpha 1 function. In this study, based on evolutionary trace method and relative solvent accessibility prediction of residues, a set of trace residues that are solvent-accessible was selected for site-directed mutagenesis. A series of GFR alpha 1 mutations was made, and PC12 cell lines stably expressing different GFR alpha 1 mutants were generated. According to the survival and differentiation responses of these stable PC12 cells upon GDNF stimulation and the GDNF- GFR alpha 1-Ret interaction assay, residues 152NN153, Arg259, and 316SNS318 in the GFR alpha 1 central region were found to be critical for GFR alpha 1 binding to GDNF and eliciting downstream signal transduction. The single mutation R259A in the GFR alpha 1 molecule simultaneously lost its binding ability to GDNF and Ret. However N152A/N153A or S316A/N317A/ S318A mutation in the GFR alpha 1 molecule still retained the ability to bind with Ret. These findings suggest that distinct structural elements in GFR alpha 1 may be involved in binding to GDNF and Ret.