Gene/Protein Disease Symptom Drug Enzyme Compound
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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The complex treatment of patients with chronic obstructive pulmonary disease (COPD) administered in a sanatorium environment is an effective therapeutic option for this condition as it involves conduction of a combination of climatic, therapeutic and rehabilitation procedures for a longer period of time. We studied the effect of this therapeutic modality on the dyspnea indices of COPD patients and the implication these indices have for the outcome of the treatment. The study was performed in the sanatorium of the State Hospital for Lung Diseases in Raduntzi, Bulgaria. It included 75 patients (65 men, 11 women) with different forms of stable COPD (mean age, 56.8 +/- 1.0 years, mean +/- SEM, FEV1% predicted--37.3 +/- 1.6%, mean duration of sanatorium stay 14 +/- 0.4 days). During the stay the patients received anti-obstructive and anti-inflammatory therapy based on the clinical discretion of the attending physician. All patients attended a rehabilitation programme according to their conditions; oxygen therapy was used in three patients. Of the 75 patients, 50 (66.7%) showed improvement at discharge, 21 (28%) had no improvement, and 4 (5.3%) were discharged in deteriorated condition. The complex treatment resulted in a minimal but statistically significant improvement of the basic spirographic and dyspnea parameters. This improvement depended not so much on the type of therapy administered as on the initial dyspnea and blood gas parameters. The body mass index (BMI) can also be used as a prognostic indicator especially if it is lower than 20 kg/m2. The lower this index is the lower the basic functional parameters are--in spite of using all available treatments, our patients with low body mass index rarely showed any noticeable improvement.
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PMID:Effect of complex sanatorium treatment on some dyspnea indices in patients with chronic obstructive pulmonary disease. 1053 15

Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene. The 5T allele in intron 8 (IVS8) causes abnormal splicing in the CFTR gene, and is associated with lung disease when it occurs in cis with a missense mutation in the CFTR gene, R117H. However, the 5T variant alone has not been reported to cause lung disease. We describe two adult female patients with CF-like lung disease associated with the 5T allele. One patient's genotype is 5T-TG12-M470V/5T-TG12-M470V, and the other is DeltaF508/5T-TG12-M470V; full sequencing of the CFTR gene revealed no other mutation on the same allele as the 5T variant. The levels of full-length CFTR mRNA in respiratory epithelia were very low in these patients (11 and 6%, respectively, of total CFTR mRNA expression). Both patients had defective CFTR-mediated chloride conductance in the sweat ductal and/or acinar epithelia (sweat chloride, mmol/L, mean +/- SEM: 40.0 +/- 5.0 [n = 8 samples] and 80. 0 +/- 3.5 [n = 6 samples]) and airway epithelia (mV, mean +/- SEM CFTR-mediated Cl(-) conductance of 1.2 +/- 2.2 [n = 5 studies] and -6.75 +/- 8.1 [n = 4 studies]). These data suggest that the 5T polythymidine tract sequence on specific haplotype backgrounds (TG12 and M470V) may cause a low level of full-length functional CFTR protein and CF-like lung disease.
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PMID:Lung disease associated with the IVS8 5T allele of the CFTR gene. 1106 35

Pulmonary fibrosis is characterized by excessive deposition of extracellular matrix proteins within the pulmonary interstitium. The new macrolide immunosuppressant SDZ RAD, a rapamycin analogue, inhibits growth-factor dependent proliferation of mesenchymal cells and might therefore be of therapeutic interest for the treatment of fibrotic lung disease. In this study the effect of SDZ RAD on lung-collagen accumulation in the bleomycin model of pulmonary fibrosis in rats was investigated. SDZ RAD (2.5 mg x kg(-1) x day(-1)) or drug vehicle were administered orally by daily gavage. Successful dosing was confirmed by measuring splenic weight. Total lung-collagen content was measured by high-performance liquid chromatographic quantitation of hydroxyproline. In animals given bleomycin and drug vehicle, total lung collagen was increased by 182+/-11% (mean+/-SEM) compared with saline controls at 14 days (p<0.001). The increase in lung-collagen accumulation was reduced by 75+/-12% (p<0.01) in animals given SDZ RAD and was accompanied by a concomitant 56+/-6% (p<0.001) reduction in lung weight. SDZ RAD is currently in clinical trials for the prevention of solid organ graft rejection, another condition characterized by excessive extracellular matrix production. The authors propose that SDZ RAD warrants evaluation as a novel therapeutic agent for fibrotic lung disease.
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PMID:The rapamycin analogue SDZ RAD attenuates bleomycin-induced pulmonary fibrosis in rats. 1210 67

Our objective was to determine the safety and efficacy of aerosol beclomethasone vs. systemic dexamethasone for extubation in premature infants at high risk for chronic lung disease (CLD). Intubated preterm infants who were identified as being at high risk for moderate-severe CLD on day 14 of life were randomized to one of four groups. The control group received systemic dexamethasone and aerosol placebo, while the other three groups received either high (2.40-3.69 microg/kg/day delivered to lungs), medium (1.0-1.85 microg/kg/day), or low (0.48-0.74 microg/kg/day) dose aerosol beclomethasone and systemic placebo. Those receiving aerosol steroids who remained ventilator-dependent after 7 days were switched to standard 42-day tapering doses of systemic dexamethasone. The primary outcome was extubation within 1 week of starting steroids, using predefined criteria. Secondary variables included changes in lung function, rates of side effects, and tracheal aspirate white blood cell counts. Sixty-one infants with birth weights of 761 +/- 18 g (mean +/- SEM) and gestational ages of 25.7 +/- 0.2 weeks were randomized to one of the four groups. Seven of 15 infants in the control systemic dexamethasone group were successfully extubated compared with 3/16 in the high-dose beclomethasone group, 1/15 in the medium-dose group, and 2/15 in the low-dose group (P < 0.01). Only dexamethasone subjects demonstrated improvements in lung function over the study period. These infants also had significant increases in blood pressure and blood glucose levels, as well as a decline in their tracheal aspirate white blood cell count. In conclusion, aerosol beclomethasone at the very low doses used in this study did not facilitate extubation in intubated premature infants at high risk for moderate-severe CLD.
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PMID:Randomized controlled trial of three different doses of aerosol beclomethasone versus systemic dexamethasone to promote extubation in ventilated premature infants. 1268 95

Although premature infants are known to be deficient in pulmonary surfactant, there is limited information regarding surfactant protein (SP) composition. To assess the postnatal profile of SPs, tracheal aspirate samples were collected from 35 intubated infants of 23-31 weeks of gestation between 8 and 80 days of age. In 71 large aggregate surfactant samples that had normal in vitro function (minimum surface tension of less than 1 mN/m by pulsating bubble surfactometry), mean +/- SEM contents of SP-A, SP-B, and SP-C (3.7 kD) were 7.1 +/- 1.4%, 1.8 +/- 0.2%, and 4.6 +/- 0.6%, respectively, of phospholipid. To assess SPs in the 1st week of life, we analyzed samples from additional infants receiving only synthetic replacement surfactant. On the 2nd day of life, contents of SP-A, SP-B, and SP-C were 13.4%, 8.4%, and 0.1%, respectively, of the mean levels for Day 8-80 samples. The major postnatal increases for SP-A, SP-B, and SP-C occurred during the 1st, 2nd, and 3rd weeks, respectively. We conclude that surfactant of newborn premature infants is markedly deficient in SPs, in particular SP-C. Despite continuing lung disease, some infants who are more than 1 week of age have surfactant with normal in vitro function that contains SPs at levels comparable to adult surfactant.
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PMID:Surfactant protein profile of pulmonary surfactant in premature infants. 1290 26

Surfactant protein D (SP-D) interacts with Aspergillus fumigatus and is strongly increased in the lavage from animals with acute allergic reactions to the fungus, suggesting a central role for SP-D. As the course of cystic fibrosis (CF) is often complicated by an allergic bronchopulmonary aspergillosis (ABPA), the authors hypothesised that SP-D may also be increased in serum during an ABPA, potentially assisting in its diagnosis and follow-up. In 22 patients with CF (11 with ABPA, 11 matched without ABPA) and 19 control patients without a pulmonary disease, SP-D concentrations in serum were assessed by an enzyme immunoassay. Serum SP-D in CF patients (130 +/- 16 ng x mL(-1) (mean +/- SEM)) was significantly higher than in the controls without lung disease (66 +/- 8 ng x mL(-1)). During the whole ABPA-episode, SP-D level did not change significantly, despite large changes of total serum immunoglobulin E. There was a clear negative correlation between SP-D concentration and overall lung function, i.e. forced expiratory volume in one second and forced vital capacity. Serum level of surfactant protein D may be of value to follow pulmonary function and lung injury in cystic fibrosis patients. Surfactant protein D serum levels are not helpful for the diagnosis and follow-up of an allergic bronchopulmonary aspergillosis episode, contrary to what was expected from animal experiments.
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PMID:Surfactant protein D in serum from patients with allergic bronchopulmonary aspergillosis. 1458 9

The "insertion" (I) rather than "deletion" (D) variant of the human angiotensin-converting enzyme (ACE) gene is associated with both lower tissue ACE activity and elite performance at high altitude. Three genotypes, II, ID and DD, are thus represented in the population. The authors examined whether an improved ventilatory response to hypoxic exercise may contribute to this effect. Subjects (n=60; 37 male, mean+/-SEM age 23.6+/-0.6 yrs, 14 II, 30 ID, 16 DD) underwent incremental cardiopulmonary exercise testing to establish maximal oxygen uptake and ventilatory threshold (VT). Four hours later, subjects exercised for 6 mins at 50% of the workload at VT. The protocol was repeated 15 mins later while breathing 12.5+/-0.5% oxygen in nitrogen. All subject characteristics were independent of genotype, as were data during normoxic exercise. However, the hypoxia-induced rise in minute ventilation was significantly greater among those of II genotype (39.6+/-4.1% versus 27.9+/-2.0% versus 28.4+/-2.2% for II versus ID versus DD, respectively). These data are supported by a significantly greater decrease in end tidal carbon dioxide (consistent with an increase in alveolar ventilation) among those homozygous for the I allele (II -18.7+/-1.3%, ID -15.7+/-0.4%, DD -15.1%+/-1.1). The ventilatory response to hypoxic exercise is influenced by angiotensin-converting enzyme genotype. Potential implications concern high altitude performance and the pathogenesis and management of hypoxic lung disease.
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PMID:Angiotensin-converting enzyme genotype and the ventilatory response to exertional hypoxia. 1462 Oct 81

The aim of the study was to measure for the first time in humans surfactant disaturated-phosphatidylcholine (DSPC) net synthesis and kinetics by using a novel, dual stable isotope tracer approach. Ten infants with congenital diaphragmatic hernia [CDH; birth weight, 3.4 +/- 0.2; gestational age, 39.8 +/- 0.4 wk] and 6 age-matched control subjects with no lung disease (birth weight, 3.2 +/- 0.3 kg; gestational age, 39.1 +/- 1.1 wk), all of whom were admitted to the neonatal intensive care unit (Padua, Italy), were studied. All infants received simultaneously an intratracheal (carbon-13 di-palmitoyl-phosphatidylcholine) and an i.v. (deuterated palmitic acid) stable isotope tracer. Isotopic enrichment curves of DSPC from sequential tracheal aspirates were analyzed by mass spectrometry. DSPC kinetic data were expressed as mean +/- SEM and compared by the Mann-Whitney test. DSPC net synthesis from plasma palmitate was nearly identical in infants with CDH and control subjects (8.6 +/- 2.2 and 8.1 +/- 1.5 mg. kg(-1). d(-1); P = 0.7). DSPC apparent pool size was 36.7 +/- 7.5 and 58.5 +/- 9.1 mg/kg (P = 0.07) and half-life was 26.7 +/- 4.5 and 50.3 +/- 9.7 h (P = 0.03) in infants with CDH and control subjects, respectively. Both DSPC turnover and percentage of catabolism/recycling significantly correlated with duration of mechanical ventilation. In conclusion, the measurements of net DSPC synthesis and catabolism/recycling were reported for the first time in humans. Mean net DSPC synthesis was approximately 8 mg. kg(-1). d(-1). No significant differences were found between control subjects and infants with CDH. DSPC turnover was faster in infants with CDH, presumably reflecting an increased DSPC catabolism/recycling. Whether this may ultimately lead to a secondary surfactant deficiency in infants with CDH is still to be ascertained.
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PMID:A dual stable isotope tracer method for the measurement of surfactant disaturated-phosphatidylcholine net synthesis in infants with congenital diaphragmatic hernia. 1518 Nov 83

Despite absence of clear proof of efficacy, the use of inhaled corticosteroids (ICS) is widespread in cystic fibrosis (CF) patients. Therefore, the effect of ICS on lung function and other clinical variables was studied in 27 prepubertal CF children with mild to moderate lung disease. In a prospective double-blind case-controlled study, fluticasone propionate 500 microg or placebo were administered twice daily during 12 months. The mean (standard error of the mean, SEM) patient age was 8.2 (0.6) years in the placebo group and 9.0 (0.5) years in the fluticasone group. The mean (SEM) forced expiratory volume in 1 s (FEV(1)) was 91% (4%) in the placebo group and 86% (4%) in the fluticasone group. There was no statistically significant difference in the evolution of lung function and the number of respiratory exacerbations between groups. However, longitudinal growth in fluticasone patients was significantly slower than in placebo patients: 3.96 (0.29) cm versus 5.49 (0.38) cm [p<0.005, analysis of variance (ANOVA)] over the 12-month study duration. This resulted in a significant change in height standard deviation score (SDS) of -0.38 (0.09) in the fluticasone group versus -0.01 (0.07) in the placebo group (p<0.003, ANOVA). No catch-up growth was noted 1-2 years after discontinuation of inhaled steroids. The use of high-dose ICS in CF patients with mild lung disease may lead to persistent growth impairment.
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PMID:Do inhaled corticosteroids impair long-term growth in prepubertal cystic fibrosis patients? 1679 99

Chronic passage of gastric and/or alimentary material into the airways is a frequent and difficult-to-diagnose condition. Because alveolar macrophages phagocytose aspirated material, it has been suggested that their identification is a useful diagnostic method. To know the usefulness of the lipid-laden alveolar macrophages (LLAM) index as a diagnostic tool for aspiration, children from 1 month to 16 years of age were included in three groups: G-I, children with pulmonary pathology and suspicion of aspiration by clinic or image evaluation; G-II, with pulmonary pathology without suspicion of aspiration; and G-III, without respiratory symptoms nor suspicion of aspiration. Bronchoalveolar lavage was obtained through bronchoscopy in G-I and G-II, and through endotracheal tube in G-III, and the LLAM index (0-400) was determined. A total of 112 patients (41, 30, and 41 in G-I to III, respectively) were studied. LLAM index (mean +/- SEM) was highest in G-I (233.2 +/- 5.5), as compared with G-II (187.8 +/- 11.6, P < 0.05), and G-III (108.5 +/- 13.5, P < 0.001). However, notable overlap of LLAM values was observed between G-I and G-II, and between G-II and G-III. When patients from G-I and G-III were jointly analyzed, the area under the ROC curve for diagnosing aspiration was 0.92, with a best cutoff value of >165 (98.6% sensitivity, 78.0% specificity, 87.8% overall accuracy). LLAM index, with a cutoff value of >165 is a useful diagnostic test for aspiration when there is suspicion of this condition. However, due to its low specificity, it does not discriminate other causes of chronic lung disease.
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PMID:Cutoff value of lipid-laden alveolar macrophages for diagnosing aspiration in infants and children. 1843 6


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