Effects of growth hormone therapy on the developmental changes of follicle stimulating hormone and insulin-like growth factor-I serum concentrations in Turner's syndrome

OBJECTIVE The aim was to investigate whether, in the absence of gonads, GH could bring forward the age of neuroendocrine activation resulting in onset of puberty. DESIGN In girls with Turner's syndrome, we evaluated the effects of GH therapy on developmental changes in FSH serum concentrations used as an indicator of neuroendocrine maturation in the absence of gonads. PATIENTS Thirty-nine girls with Turner's syndrome aged 4.0-17.1 years were treated using GH (25 IU/m² week) for 1 year. MEASUREMENTS Serum levels of FSH and IGF-I were measured before initiation of GH therapy and 12 months later, after interruption of GH treatment for 2 days. RESULTS Pretreatment FSH levels were low between 6 and 10 years and increased markedly at 10-11 years of age. This pattern was unchanged after 1 year of GH therapy. Pretreatment IGF-I levels were positively correlated with age and they were uniformly increased after 1 year of GH therapy. CONCLUSIONS Our data suggest that GH and its effector, IGF-I, do not influence the timing of the onset of puberty through an effect on its neuroendocrine control.     

Labeling of human lymphocytes with 99mTc by means of stannous pyrophosphate. Scintigraphic applications

An original ^99mTc-labeling method applied to human lymphocytes is described. This technique is based on the use of stannous pyrophosphate to reduce sodium pertechnetate. The proposed procedure has two main advantages: firstly, the labeling process takes place in a neutral and buffered medium which prevents any cellular aggregation; secondly, the labeling yield obtained is compatible with scintigraphic studies in man. The influence of each parameter on the labeling quality had been studied as well as the binding stability of the technetium fixed on cells. A systematic study of lymphocyte surface markers, before and after labeling, has led to the suggestion that the labeling process seems to affect cellular membranes, probably because of the technetium binding. Finally, scintigraphic results are presented, the study being performed on eight healthy volunteers. These results are compared with those published by other authors who used either a different radioisotope or a different labeling method.     

Improved survival and marrow engraftment of mice transplanted with bone marrow of GM-CSF-treated donors

Abstract: Recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) administered to bone marrow (BM) transplant recipients is associated with earlier recovery. We have investigated the possibility of stimulating normal donor mice in vivo with GM-CSF. Donor balb/c mice were injected i.p. with GM-CSF (5000 u) or saline. Seventy-two hours later 5 × 10⁵ BM cells from either GM-CSF-treated or control donors were infused into lethally irradiated (850 R) recipients. In the recipients of BM from GM-CSF-treated donors, significantly higher CFU-S and significantly higher survival rate (57% [n = 65]; vs. 30% [n = 63]; p<0.05) were noted. Donor mice of the GM-CSF group did not differ in bone-marrow cellularity and composition from their controls. However, recipients of BM from GM-CSF-treated mice had higher blood counts of haemoglobin, leukocytes and platelets compared to controls. These data demonstrate that pretreatment of BM donors with GM-CSF may be of benefit in improving survival and marrow engraftment in mice.     

Evaluation of the solid phase competition ELISA for detecting antibodies against the six foot-and-mouth disease virus non-O serotypes

The solid-phase competition ELISA (SPCE) has been evaluated in both screening and titration assay formats for detecting antibodies against foot-and-mouth disease virus (FMDV) for the six non-O serotypes A, C, SAT 1, SAT 2, SAT 3 and Asia 1. Cut-off values were determined as a percentage inhibition of 40 for the SAT serotypes and 50 for serotypes A, C and Asia 1, which gave rise to specificity values ranging from 99.41% to 99.9% for the different serotypes. The relative sensitivity between the SPCE and LPBE/virus neutralisation test was 100%/109%. Antiserum titres derived by the SPCE for samples of serotypes O, A(22) and Asia 1 were more than 11, 1 and 5 times of those determined by virus neutralisation test, respectively. This study indicated that the non-type O SPCEs have sufficient sensitivities and specificities for use as serological diagnostic tests for the qualitative and quantitative detection of antibodies against FMDV.     

Cystic fibrosis transmembrane conductance regulator function is suppressed in cigarette smokers

RATIONALE: Cigarette smoke extract inhibits chloride secretion in human bronchial epithelial cells. Oxidants decrease gene expression, protein expression, and function of the cystic fibrosis transmembrane conductance regulator (CFTR). OBJECTIVES: Because cigarette smoke is a rich source of oxidants, we verified the hypothesis that CFTR may be suppressed by exposure to cigarette smoke in vitro and in vivo. METHODS: The effects of cigarette smoke exposure on Calu-3 and T84 cell CFTR expression and function were observed. Also studied were the nasal potential differences (PDs) in 26 men (9 smokers, 17 nonsmokers) who had no detectable CFTR gene mutations as determined during investigations for infertility. CFTR expression and function were determined by Northern blotting, Western blotting, and cAMP-dependent 125I efflux assays. Extensive CFTR genotyping was performed in each subject. Nasal PD measurements were made at baseline and during amiloride, chloride-free buffer, and isoproterenol perfusions. MAIN RESULTS: Cigarette smoke decreased CFTR expression and function in Calu-3 and T84 cell lines. Furthermore, the nasal PDs of cigarette smokers showed a pattern typical of CFTR deficiency with a blunted response to chloride-free buffer and isoproterenol compared with nonsmokers (-9.6 +/- 4.0 vs. -22.3 +/- 10.1 mV; p < 0.001). CONCLUSIONS: We conclude that cigarette smoke decreases the expression of CFTR gene, protein, and function in vitro and that acquired CFTR deficiency occurs in the nasal respiratory epithelium of cigarette smokers. We suggest that acquired CFTR deficiency may contribute to the physiopathology of cigarette-induced diseases such as chronic bronchitis.     

The analysis of quantitative expression of somatostatin and dopamine receptors in gastro-entero-pancreatic tumours opens new therapeutic strategies

OBJECTIVE: Somatostatin (sst) are present in the majority of gastro-entero-pancreatic (GEP) tumours. Effects of somatostatin receptor (sst) analogues are partial and of limited duration. Cell lines derived from GEP express dopaminergic receptors D(2). New chimeric analogues simultaneously recognising sst(2) and sst(5) or sst(2) and D(2) have additive effects in inhibition of GH and prolactin secretion in pituitary adenomas. Our aim was to quantify the expression of sst and D(2) mRNA in human GEP tumours. DESIGN AND METHODS: mRNA expression of sst(1), sst(2), sst(3) and sst(5) as well as D(2), was analysed using real-time PCR (TaqMan probe) in a series of 35 patients with GEP tumours (pancreas (n = 19) and intestinal (n = 16)). Levels of expression were compared with a group of 13 somatotroph adenomas. RESULTS: All GEP tumours express sst(1), sst(2) and D(2). Expression of sst(3) and sst(5) was observed in 89 and 76% of tumours respectively with highly variable levels. sst(2) mRNA expression was higher in nonfunctional tumours (P < 0.009) and sst5 was higher in pancreatic than in intestinal tumours (P < 0.02). Whereas sst(2) levels were similar between GEP and somatotroph tumours, levels of sst(5) and D(2) were higher in the former (394.9 +/- 156.1 x 10(-2) vs 69.7 +/- 19.5 x 10(-2) copy/copy beta-Gus (P < 0.0036) and 519.6 +/- 121.2 x 10(-2) vs 50.0 +/- 21.6 x 10(-2) copy/copy beta-Gus (P < 0.0001) respectively). In small tumours ( < 30 mm), sst(2) density appeared as a crucial parameter in somatostatin receptor scintigraphy results, whereas in big tumours, a consistent bias in SRS results was introduced by the size. In pancreatic GEP, high-level sst(3) expression was found in tumours with more active angiogenesis (higher microvessel density and vascular endothelial growth factor expression (P < 0.03)). CONCLUSIONS: GEP tumours co-express sst(2) and D(2) in 100% of cases and sst(5) in 89% thus supporting the testing of bi-specific agonists (sst(2)/sst(5) or sst(2)/D(2)) in these tumours.     

Autonomic dysreflexia and telehealth

With the rapid expansion of telehealth lines in the United States and the establishment of provincially funded lines in Canada, a growing number of people use this convenient approach to establish their initial health needs and to pursue self-care. Telehealth providers, for the most part, rely on electronic protocols to offer triaging and advice. Unfortunately, standard protocols are misleading when a premorbid health condition such as a spinal cord injury is present. Symptoms such as a headache, diaphoresis or an elevated blood pressure, which are common occurrences in the general population, may indicate an emergency situation, namely autonomic dysreflexia (AD), when a mid-thoracic and higher spinal cord lesion is present. Since there is no available electronic protocol on AD, this emergency health condition is not recognized by the telehealth provider and may put the caller at risk of serious morbidity or even death. In this article, the authors present the clinical features of AD, the precipitating factors and the nursing management of an episode. The merits and pitfalls of electronic protocols are reviewed and an algorithm is presented to assist telehealth providers in recognizing AD.     

Severe gastrointestinal inflammation in adult dermatomyositis: characterization of a novel clinical association

OBJECT: Gastrointestinal involvement in adult dermatomyositis (DM) and polymyositis (PM) is usually mild, resulting from myoenteric dismotility. Severe inflammation of the alimentary tract in cases of adult DM and PM is rare. The purpose of this study was to examine the prevalence and clinical characteristics of inflammatory gastrointestinal involvement in patients with DM. METHODS: The charts of all cases with polymyositis or dermatomyositis, registered in our rheumatology clinic between 1984 and 2004, were reviewed retrospectively for documentation of severe gastrointestinal involvement. The clinical course and the histopathologic findings in all the patients were noted, and the prevalence of this disorder was computed. RESULTS: Among 48 patients with DM or PM, 3 patients with DM and severe gastrointestinal tract manifestations were identified (6% of the study population). Edematous hyperemic bowel wall, with multiple erosions and ulcerous lesions were the prominent endoscopic findings, whereas diffuse mucosal inflammation and multiple vascular ectasias without vasculitis dominated the histologic picture. The resulting clinical course was notable for recurrent abdominal pain and bloody diarrhea, ending catastrophically in two patients with fatal gastrointestinal perforations, despite aggressive immunosuppressive therapy. CONCLUSIONS: Severe inflammatory gastrointestinal tract disease should be recognized as a grave, albeit rare, manifestation of adult DM that portends a poor prognosis and carries a high rate of fatal complications. The role of vasculopathy in the pathogenesis of this syndrome remains to be determined.     

EVALUATION OF THE HEALTH RISK ASSOCIATED WITH EXPOSURE TO CHLOROFORM IN INDOOR SWIMMING POOLS

The exposure of swimmers to chloroform (CHCl₅) was investigated in indoor swimming pools of the Quebec City region along with the associated carcinogenic risk. Six training sessions involving 52 competition swimmers (11 to 20 yr old) were conducted in 3 different pools, while 12 adult leisure swimmers attended 5 sessions, each held in a different pool. For each session, water and ambient air CHCl₃ concentrations were measured and CHCl₃ levels in alveolar air samples (CHCl₃ALV) collected from swimmers prior to entering the swimming pool premises and after 15, 35, and 60 min of swimming. Mean water concentrations varied from 18 µg/L to 80 µg/L, while those in air ranged from 78 µg/m3 to 329 µg/m3. Multiple linear regression analyses revealed that CHCl₃ALV values in competition swimmers were strongly correlated to ambient air and water levels, and to a lesser degree to the intensity of training. Only ambient air concentration was positively correlated to CHCl₃ALV in the leisure group. Concentrations of CHCl₃ metabo lites bound to hepatic and renal macromolecules, estimated using a physiologically based pharmacokinetic (PBPK) model, were 1.6 and 1.9 times higher for the competition swimmers than for the leisure swimmers, respectively. The highest hepatic concentration predicted in competition swimmers, 0.22 µg CHCl equivalents/kg of tissue, was at least 10,000 times lower than the smallest no observed³effect level for liver tumors in animals. Data indicate that the safety margin is therefore very large, for competitive swimmers as well as for leisure swimmers.