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Biomedical subjects

Michael Barker

Publications and source records attributed to Michael Barker.

9 recordsLinked to original sources
PubMed2006

Value of virtual tracheobronchoscopy and bronchography from 16-slice multidetector-row spiral computed tomography for assessment of suspected tracheobronchial stenosis in children.

PURPOSE: To evaluate the value of dose-reduced 16-slice multidetector-row spiral computed tomography (16-MDCT) using virtual tracheobronchoscopy (VTB) and virtual bronchography (VBG) in children with suspected tracheobronchial stenosis. MATERIALS AND METHODS: 12 children (4 d to 3 years, body weight 1.2 kg to 13.5 kg) with stridor and suspected tracheobronchial stenosis were examined by contrast-enhanced low-dose 16-MDCT. Conventional axial slices, MPRs, VTB, and VBG were calculated. Image findings were correlated with the results of fiberoptic bronchoscopy (12 out of 12) as a gold standard and subsequent surgery (8 out of 12). RESULTS: VTB and VBG demonstrated the fiberoptic bronchoscopically suspected tracheal stenosis in 11 of 12 children due to vascular compression because of the brachiocephalic trunk (6), a double aortic arch (2), a vascular compression of the left main bronchus (2), and a right aberrant subclavian artery (1). Eleven out of 12 stenoses were correctly depicted by conventional axial slices, MPRs, VTB, and VBG. Dose reduction was 79 to 85.8% compared to a standard adult chest CT. CONCLUSION: Dose-reduced 16-MDCT with the use of VTB and VBG is effective for the evaluation of tracheobronchial stenosis in children and correlates well with fiberoptic bronchoscopy.

Airway Obstruction↗
PubMed2006

Coinheritance of Gilbert syndrome-associated UGT1A1 mutation increases gallstone risk in cystic fibrosis.

The prevalence of "black" pigment gallstones is increased in patients with cystic fibrosis (CF). Bile acid malabsorption with augmented bilirubin uptake from the intestine and the development of "hyperbilirubinbilia" have been proposed as key factors in gallstone formation in CF patients. We have now tested the hypothesis that the coinheritance of the common UGT1A1 promoter mutation associated with Gilbert syndrome is an additional lithogenic risk factor for gallstone formation in CF. Our results show that patients with CF and gallstones are significantly more likely to carry at least one Gilbert UGT1A1 allele compared with stone-free patients (OR 7.3; P = .042) and that these carriers display significantly higher serum levels of unconjugated bilirubin (P = .002). In conclusion, the Gilbert UGT1A1 allele increases the risk of gallstone formation in CF. This genetic association supports the current concept for gallstone formation in CF and suggests that genetic and exogenous sources contributing to hyperbilirubinbilia might be lithogenic in CF patients.

Adolescent↗
PubMed2005

Prevalence of thrombophilia and catheter-related thrombosis in cystic fibrosis.

Venous thrombosis in children and young adults is frequently associated with predisposing conditions and with an indwelling catheter or totally implantable venous access device (TIVAD). These systems are commonly used for the delivery of antibiotic therapy in patients with cystic fibrosis (CF). We reviewed our CF center's history of catheter-related events over 13 years and prospectively investigated the presence of risk factors for thrombosis in 66 children and adults with CF (age, 3-38 years; 32 females). Five thrombotic events had occurred in 4 patients, 2 of whom carried the factor V Leiden mutation. Five asymptomatic patients were diagnosed with heterozygous mutations of the factor V or prothrombin gene. Functional activity of protein C was decreased in 13 subjects, with a correlation to impaired liver function. Protein S activity was abnormal in 20 patients and was related to CF genotype. Anti-phospholipid antibodies (APA) were present in 6 asymptomatic patients. A reinvestigation after 3 years confirmed protein S deficiency in 12 of 14 patients, while most abnormalities for protein C or APA were inconsistent. In conclusion, a thrombophilic state was detected in 53% of patients, and 2 out of 4 subjects with TIVAD-related thrombosis carried a genetic defect. It may thus be helpful to include a hemostatic evaluation in the clinical decision process for or against TIVAD insertion in eligible CF patients.

Adolescent↗
PubMed2004

Exercise testing and training in German CF centers.

Physical exercise is increasingly recognized as a valuable diagnostic and therapeutic modality for patients with cystic fibrosis (CF). We sought to characterize the use of exercise testing and training as well as the attitude toward both issues through a national survey. A questionnaire was sent to 107 specialized CF centers (caring for a total of 5,231 patients) and 7 inpatient rehabilitation institutions. Answers were available from 62 specialized centers caring for 3,580 patients and from 4 rehabilitation centers with 520 treatment episodes per year. Sixty percent of specialized centers performed some sort of exercise testing at an average frequency of 1 in 2.3 years for patients aged 8 and above. However, protocols and indication criteria were often unstandardized or not specified at all. Equipment availability was no major problem, and the majority of tests were conducted by a physician alone. Nineteen centers had adopted exercise testing as part of their diagnostic routine. Two thirds of caregivers advised their patients to engage in physical activity, but failed to discuss specific modalities and potential hazards. Nevertheless, physical exercise was viewed as "extremely important" or "very important" by 87%. In a rehabilitation setting, an exercise test was conducted 1.1 times per patient stay, and a training program offered in 100% of cases. In conclusion, standardized exercise testing and training programs appear to be underused in German CF centers, despite a high degree of interest in the topic. Supplementary material for this article can be found on the Pediatric Pulmonology website (http//www.interscience.wiley.com/jpages/8755-6863/suppmat).

Adult↗
PubMed2004

Effect of DNase on exercise capacity in cystic fibrosis.

DNase can reduce viscosity and facilitate expectoration of airway secretions in cystic fibrosis (CF) lung disease. We evaluated its effect on exercise performance in relation to resting pulmonary function. Fifteen sputum-producing CF patients (aged 9-28 years; FEV1 22-83% predicted) performed spirometry, body plethysmography, nitrogen washout, and incremental cardiopulmonary exercise testing before and after 8 weeks of first-time treatment with daily inhaled rhDNase. Most subjects reported increased amounts and fluidity of sputum. The effect on objective parameters was heterogeneous, without statistical significance. Groupwise, FEV1 increased by 6% without correlation to baseline values; individual patients gained up to 40%. Indices of hyperinflation and air trapping were slightly raised. Maximal workload and oxygen uptake (V'O2) increased by up to 20% in a number of patients. The treatment effect on V'O2 was neither related to baseline levels of pulmonary function and exercise capacity nor to the change in FEV1. Ventilatory equivalents for oxygen and carbon dioxide during exercise were slightly but insignificantly lower after DNase treatment; minimal O2 saturation was unaffected. We conclude that improvement of exercise performance with DNase is restricted to a subgroup of CF patients and may not be predicted or identified by spirometry and subject report alone.

Administration, Inhalation↗
PubMed2004

Toxicity of trans-nonachlor to Sprague-Dawley rats in a 90-day feeding study.

The chlordane constituent trans-nonachlor and its metabolite oxychlordane are among the most persistent chlordane-related contaminants and are found in tissues and milk from humans ingesting diets high in Arctic marine mammal fat. Although chlordane is no longer registered in North America, there is a need for toxicological data on chlordane-related contaminants found in food and the environment which are either structurally different or relatively more abundant than the constituents of the original chlordane mixture. Thus, a feeding study was undertaken to provide toxicological data on trans-nonachlor. Male and female Sprague-Dawley rats were exposed to 0, 5, 13 or 50 ppm trans-nonachlor in feed for 90 days and clinical, hematological and histopathological changes were assessed in each rat. Female rats were less able than males to metabolize and eliminate trans-nonachlor and, as a result, accumulated more trans-nonachlor in their adipose tissues. trans-Nonachlor, like technical chlordane and other organochlorines, induced liver microsomal enzymes in a pattern similar to phenobarbital. Endocrine effects included functional and morphological changes in the thyroid and adrenals. In male rats exposure to trans-nonachlor was associated with changes in endpoints indicative of increased oxidative stress, which may be related to both direct action on cellular targets or to secondary effects resulting from cytochrome P450 induction. The results indicate that subchronic trans-nonachlor exposure in rats induced hepatic changes with far-reaching metabolic and endocrine effects. Differences in target organ responses in male and female rats indicate that the sex-related metabolic differences affecting trans-nonachlor bioaccumulation and elimination merit further study.

Adipose Tissue↗
PubMed2003

Toxicity of the chlordane metabolite oxychlordane in female rats: clinical and histopathological changes.

Due to widespread usage of the pesticide chlordane until the 1980's, this toxic and persistent mixture has accumulated in the food chain. The Arctic acts as a global sink for these and other persistent organic pollutants, which bioaccumulate in the marine and freshwater food chains. As a result, humans consuming diets high in Arctic fish and marine mammal fat can ingest higher levels of chlordane contaminants than humans consuming "southern" diets. The most abundant constituents of the chlordane mixture are trans-chlordane, cis-chlordane, trans-nonachlor, cis-nonachlor and heptachlor; oxychlordane is the major metabolite of the chlordanes and nonachlors. In humans the predominant chlordane-related contaminants detected in breast milk and adipose tissues are trans-nonachlor and oxychlordane. The present studies were undertaken to provide toxicological data on oxychlordane for the purpose of clarifying target organ toxicity and risks to human health associated with ingesting contaminated foods. Female rats were gavaged with oxychlordane at doses ranging from 0.01 to 10 mg/kg body weight/day for up to 28 days. In terms of general toxicity oxychlordane had a steep dose-response curve: 10 mg/kg oxychlordane was acutely toxic and 1 mg/kg oxychlordane caused no measurable effects. Weight loss, reduced feed consumption and thymic atrophy were the hallmarks of acute oxychlordane toxicity. At lower doses rats showed signs of hepatic changes indicative of microsomal enzyme induction. Oxychlordane was more bioaccumulative and was toxic at levels approximately 8 times lower than trans-nonachlor and cis-nonachlor. Thus, ingestion of trans-nonachlor and related chlordane contaminants in foods results in the formation of a metabolite that is more toxic and bioaccumulative than the parent contaminants.

Administration, Oral↗
PubMed2002

An evaluation of a single chest physiotherapy treatment on mechanically ventilated patients with acute lung injury.

BACKGROUND AND PURPOSE: Acute lung injury is a lung pathology that presents frequently on the intensive care unit. Chest physiotherapy, in the form of endotracheal suction, alternate side-lying and manual hyperinflation, is usually given to patients with this condition with the intention of removing retained pulmonary secretions and recruiting collapsed distal lung units. Despite this common practice there is insufficient research on the effects of chest physiotherapy in patients with acute lung injury being ventilated mechanically. The aim of the present study was to further understanding of the effects of three modes of treatment in chest physiotherapy in an acute lung injury patient group. METHOD: This randomized, controlled trial investigated all mechanically ventilated patients with acute lung injury admitted to the adult intensive care unit at Guy's and St Thomas' NHS Trust between August 1996 and July 1997, who matched the inclusion criteria. Patients were randomized into one of three treatment groups: Group 1 (suctioned only); Group 2 (positioned and suctioned); and Group 3 (positioned, manually hyperinflated and suctioned). Baseline and 10, 30 and 60 minutes' post-treatment data were recorded for dynamic pulmonary compliance, arterial blood gases and haemodynamic variables. Results were analysed by use of an SPSS software package with a repeated-measures analysis of variance (ANOVA). RESULTS: Eighteen patients fitted the inclusion criteria. Significant changes were observed in both PaCO2 (p = 0.026) and dynamic compliance (p = 0.019) over time for all three groups. The arterial oxygen to fraction of inspired oxygen ratio (PaO2:FiO2) did not alter significantly in any of the groups. With respect to other oxygenation parameters, mixed venous oxygen saturation (SvO2) showed a significant difference between the groups. Heart rate (HR) and systemic blood pressure (BP) showed statistically significant, but not clinically significant differences over time. CONCLUSIONS: Patients with acute lung injury are notably complex to nurse and may require protracted physiotherapy intervention, which may take many forms. As de-recruitment was the single most important event that occurred in the present study population, a prescriptive chest physiotherapy approach to treating mechanically ventilated patients with acute lung should be questioned and adapted accordingly.

Aged↗