Biomedical subjects
F Moran
Publications and source records attributed to F Moran.
Non-invasive ventilation for cystic fibrosis.
BACKGROUND: The use of non-invasive ventilation (NIV) has been proposed as a means to temporarily reverse or slow the progression of worsening respiratory failure in cystic fibrosis (CF). OBJECTIVES: To compare the effect of NIV versus no NIV in people with CF. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. The reference lists of each trial were searched for additional publications that may contain other trials. Date of most recent search: January 2002. SELECTION CRITERIA: Relevant randomised controlled trials in which a form of pressure preset or volume preset NIV versus no NIV was used in people with acute or chronic respiratory failure in CF. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for inclusion criteria, methodological quality and data extraction. MAIN RESULTS: Six trials were identified and four trials met the inclusion criteria with a total of 55 participants. All of these trials only evaluated single treatment sessions. Two trials (36 participants) evaluated the use of NIV for airway clearance compared with an alternative physiotherapy method. These trials showed that airway clearance may be easier and people with CF may prefer to use NIV for airway clearance. There was no evidence that NIV increases sputum expectoration or improves lung function. Two trials (19 participants) evaluated the use of NIV for overnight ventilatory support. Of the primary outcomes examined in this review, only lung function was evaluated within the two trials. Due to the small numbers of participants and the differing statistical techniques used within the review and the primary trials, there were discrepancies in the results obtained by the RevMan analysis and the original trial analysis. No clear differences were found between NIV compared with either oxygen or room air. REVIEWER'S CONCLUSIONS: Non-invasive ventilation may be a useful adjunct to other airway clearance techniques, particularly in people with CF who have difficulty expectorating sputum. Non-invasive ventilation when used in addition to oxygen may improve gas exchange during sleep to a greater extent than oxygen therapy alone in moderate to severe disease. These benefits of NIV have only been demonstrated in single treatment sessions and its efficacy, safety and acceptability in the longer term are unknown. There is a need for long-term randomised controlled trials to determine the clinical effects of non-invasive ventilation in CF.
Incontinence in adult females with cystic fibrosis: a Northern Ireland survey.
The objectives of this survey were to establish the prevalence, onset, severity and impact of incontinence and attitudes towards the availability of advice and treatment in female adults with cystic fibrosis (CF) in Northern Ireland. All female patients (n=59) at the Northern Ireland Regional Adult CF Centre were posted a questionnaire on incontinence. Leakage of urine occurred in 14/46 respondents. Leakage of urine occurred when chest was bad in 8/14 patients and when chest was good or bad in 3/14 patients. Patients reported that their bladder problem affected their ability to perform airway clearance or cough (13/14), and exercise (4/14). The main reason given for the patients who did not seek help for their incontinence (10/14) was that they were too embarrassed. This study highlights that patients with CF are reluctant to seek treatment for incontinence despite the impact this condition can have.
Physical training for bronchiectasis.
BACKGROUND: The pathophysiology of bronchiectasis may result in the development of dyspnoea and decreased exercise tolerance, both of which can impact on a patient's quality of life and ability to perform activities of daily living. There is little information regarding the benefits of physical training in bronchiectasis: however it is probable that the benefits of physical training in bronchiectasis are at least comparable to benefits demonstrated in other respiratory conditions. There is also no information regarding the effects of non-adherence to prescribed physical training in bronchiectasis. However as in patients with COPD non-adherence may contribute to a deterioration in the patient's condition and conceivably the long term prognosis. OBJECTIVES: The objective of this review is to determine whether a prescribed regime of physical training produces improvements or prevents deterioration in physiological and clinical outcomes in bronchiectasis compared to no physical training. SEARCH STRATEGY: We searched the Cochrane Airways Group specialised register and the Cochrane Controlled Clinical Trials Register. SELECTION CRITERIA: Randomised or quasi randomised controlled trials in which a prescribed regime of physical training are compared to no physical training in patients with bronchiectasis. DATA COLLECTION AND ANALYSIS: Three studies were identified. One was did not meet the inclusion criteria and two appeared in abstract form only. More comprehensive data will be incorporated into this review once data from those two trials are published, and when further data is made available to the authors of this review. MAIN RESULTS: Results from the two studies published in abstract showed that inspiratory muscle training compared to sham or no inspiratory muscle training improved endurance exercise capacity: Weighted Mean Difference (WMD) 264 metres (95% CI 16.4 to 512 metres). PiMax improved: WMD 25 cms H20 (95% CI 11.6 to 38.4 cms H2O )as did quality of life measured with the CRQ: WMD 12.4 units (95% CI 2.4 to 22.5 units). REVIEWER'S CONCLUSIONS: This review only provides evidence of the benefits of inspiratory muscle training and provides no evidence of the effect of other types of physical training (including pulmonary rehabilitation) in bronchiectasis.
Physical training for cystic fibrosis.
BACKGROUND: Physical training may form an important part of the care package for patients with cystic fibrosis. OBJECTIVES: To determine whether a prescribed regime of physical training produces improvement or prevents deterioration in physiological and clinical outcomes in cystic fibrosis compared to no training. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group specialist trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. Date of the most recent search: August 2001. SELECTION CRITERIA: All randomised controlled clinical trials in which a prescribed regime of physical training is compared to no physical training in patients with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, assessed methodological quality and extracted data. MAIN RESULTS: Of the sixteen trials identified six trials, which included 184 patients, met the inclusion criteria. Exercise tolerance in the short term, during an acute admission was improved in patients who received physical training. In a three year study there was no improvement in exercise tolerance at the end of the study period. Over three years there was a significantly greater mean annual rate of decline in FVC in the control group compared to the exercise group WMD 2.17 (95%CI 0.47, 3.87). Changes in other lung function parameters showed a similar trend, but these were not statistically significant. REVIEWER'S CONCLUSIONS: Conclusions about the efficacy of physical training in cystic fibrosis are limited by the small size, short duration and incomplete reporting of most of the trials included in this review. Physical training is already part of the care package offered to most patients with cystic fibrosis and there is no evidence to actively discourage this. Further research is needed to assess comprehensively the net benefit of the addition of physical training to the care of cystic fibrosis patients.
Zonal expression of endothelial nitric oxide synthase in sheep and rhesus adrenal cortex.
There is mounting evidence that nitric oxide (NO) may inhibit adrenal steroidogenesis by binding to the heme group of P450 enzymes, particularly the rate-limiting steps cholesterol side-change cleavage P450, aldosterone synthase P450, and 17 alpha-hydroxylase/C(17/20)-lyase P450. Using immunohistochemistry, nitrotyrosine was detectable throughout the ovine adrenal cortex, and endothelial NO synthase (eNOS) was further identified in zona glomerulosa (ZG) and at a higher level throughout the zona fasciculata, increasing toward the medulla. Caveolin-1, 90-kDa heat shock protein, ERK-1/2, and Akt, all known and proposed regulators of eNOS activity, were detected throughout the ovine adrenal cortex. Western immunoblotting confirmed the identity of these proteins as well as the absence of neuronal NOS, inducible NOS, caveolin-2, and caveolin-3. Through dual immunostaining we further identified for the first time a zona intermedia without strong staining for 17 alpha-hydroxylase/C(17/20)-lyase P450 or angiotensin II type 1 receptor, but positive for eNOS. Rhesus adrenals also stained positively for eNOS, but staining was seen only in the ZG and zona reticularis. We conclude that eNOS may play a role in controlling zone-specific aldosterone synthase vs. 11 beta-hydroxylase activities of the single CYP11B gene in sheep. In the rhesus monkey, NO may modulate ZG aldosterone synthase, but it is not needed for control of the distinct 11 beta-hydroxylase in the zona fasciculata. In the zona reticularis, however, eNOS may control C(19) steroid production at the level of 17 alpha-hydroxylase vs. 17,20-lyase activity otherwise unopposed by 3beta-hydroxysteroid dehydrogenase.
Interruption of estradiol signal transduction by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) through disruption of the protein phosphorylation pathway in adipose tissues from immature and mature female rats.
At doses of 10-115 microg/kg, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) decreased body and adipose tissue weights of mature female rats. Doses below 10 microg TCDD/kg decreased body and adipose tissue weights of immature, but not mature females. Doses of 2 and 10 microg TCDD/kg decreased adipose tissue epidermal growth factor receptor (EGFR) binding activity 5 and 7 days later in immature and mature females, respectively. At these times, there was a decrease in the activities of tyrosine kinase (TK), mitogen-activated protein kinase (MAP2K), and protein kinase A (PKA). In mature females, estradiol (E2, 15 microg/kg) increased TK and PKA activities and decreased MAP2K activity. In immature females, E2 decreased TK and PKA activities but not MAP2K activity. TCDD abolished the stimulatory effect of E2 on TK and PKA in mature females, and in immature females TCDD potentiated the negative effect of E2 on all three kinases. TCDD decreased binding of [3H]E2 to cytosolic and nuclear estrogen receptors (ERs) of mature and immature females, and antagonized the stimulatory effect of E2 on ER binding activity. E2 increased DNA binding activity of the estrogen response element (ERE) and activator protein-1, and TCDD antagonized this effect. Geldanamycin, an inhibitor of Src tyrosine kinase, reduced the effects of TCDD on body and adipose tissue weights. Geldanamycin antagonized the effects of TCDD on EGFR binding activity and TK activity. In cell-free preparations, TCDD antagonized E2 action on TK activity in mature females, as well as E2 action on PKA activity in immature females. We hypothesize that TCDD antagonizes E2 action in female adipose tissues through disruption of common cytosolic signal transduction pathways.
Growth retardation in premenarchial female rhesus monkeys during chronic administration of GnRH agonist (leuprolide acetate).
Leuprolide acetate in depot form (0.75 mg/kg body weight/month, i.m.) was administered to four female rhesus monkeys from 18-30 months of age, a period that includes the premenarchial growth spurt. They were compared to eight age matched controls. As anticipated, sexual maturation was blocked in the Leuprolide group and menarche did not occur. Growth was also severely retarded; no weight gain occurred during the study in the Leuprolide group as compared to a 25% weight gain (P = .044) in the control group. The Leuprolide group also lost muscle mass. Food intake normalized for body weight was not affected. Linear growth averaged 35% less in the Leuprolide group. Serum IGF-1 concentrations increased from 486 +/- 84 to 965 +/- 47 ng/mL (P = .0025) in the Leuprolide group and from 838 +/- 139 to 3,006 +/- 545 ng/mL (P = .0016) in the control group. These data suggest that premenarchial pituitary/gonadal suppression results in a distinctive pattern of growth retardation in monkeys.
Response of cynomolgus macaques to immunization against a synthetic peptide from the human zona pellucida.
This study tested immunogenicity of a synthetic peptide hZP3(327-341) from a human zona pellucida (ZP) glycoprotein. After antibody response to various peptide-carrier conjugates was assessed in mice, two female cynomolgus macaques were immunized with the peptide conjugated to keyhole limpet hemocyanin (KLH). A control macaque was immunized with KLH. The peptide was immunogenic in both species, and included both B and T cell epitopes since low to moderate titers of peptide-specific antibodies and a T cell proliferative response were measured. Profiles of ovarian steroid metabolites indicated unchanged ovarian function in the macaques, but only the control conceived when bred. Ovarian histology was normal except that immunoglobulin was bound to ZP in follicles of the peptide-immune macaques. ZP from these females bound sperm and induced acrosome reactions at rates equal to those of an untreated control. The results support the feasibility of an immunocontraceptive vaccine based on autologous ZP peptides.
An evaluation of integrated cardiopulmonary exercise testing in a pulmonary function laboratory.
Clinical exercise testing has been used mainly to assess the cardiac response to exercise. Integrative cardiopulmonary exercise tests (CPET) involving the measurement of the ventilatory, circulatory and metabolic response to exercise has largely been a research tool. We analysed the results of one hundred tests randomly chosen from a total of 472 exercise tests performed between January 1992 and June 1993 as clinical investigation in a pulmonary function laboratory. CPET was used (a) to identify the cause of effort limitation in patients where more than one illness could be relevant (26); (b) to obtain an objective measure of the exercise capacity of patients with respiratory or cardiac disease (31); (c) as monitor of response to treatment (11) and (d) in the investigation of unexplained dyspnoea (32). In 94 of the 100 cases CPET was able to provide an answer to the specific clinical question posed. In patients with unexplained dyspnoea (CPET identified a group who exhibit an inappropriate hyperventilatory response to exercise with no supportive evidence of cardiopulmonary disease. In a small minority of cases CPET gave non-specific results. We conclude that CPET is a useful investigation in the management of patients with cardiopulmonary disease and complements the various other investigations offered by a pulmonary function laboratory.
Luminescence luteinizing hormone/choriogonadotropin (LH/CG) bioassay: measurement of serum bioactive LH/CG during early pregnancy in human and macaque.
Because of the microheterogeneities of gonadotropins, measurement of immunoreactivity of these glycoproteins does not necessarily reflect changes in their bioactivity. In addition, LH bioactivities in human samples analyzed by a rodent LH bioassay have been discordant with findings based on human granulosa-luteal cells. We have isolated a human LH/choriogonadotropin (CG) receptor cDNA and expressed the recombinant protein. Using 293 cells permanently transfected with the human LH receptor cDNA and a luciferase reporter gene driven by a cAMP-dependent promoter, we have developed a luminescence LH/CG bioassay. After cells were treated with human LH or CG for 20 h, luciferase activity was measured through use of a luminometer. Luciferase activity in the cells was increased in a dose-dependent manner. In contrast, treatment with FSH, thyroid-stimulating hormone, prolactin, growth hormone, adrenocorticotropin, insulin, prostaglandins, and several neurotransmitters had no effect. Because treatment with basic fibroblast growth factor (bFGF) caused significant increases in basal luciferase activity, a fixed amount of bFGF was included in all reactions. Incubation with 0.1 to 30 microliters serum from women during different physiological states stimulated the luciferase activity in parallel with the hCG standard curve. In 4 conception cycles, bioactive LH/hCG levels began to increase 2 wk after the midcycle LH surge, followed by a logarithmic increase from 22 days on. Due to the lack of a homologous RIA for measuring CG levels in monkeys, we analyzed serum bioactive monkey CG (mCG) in macaque during early pregnancy. Bioactive mCG was detected about 12 days after the midcycle LH surge and fertile mating and persisted until Days 21-23, followed by a decline.(ABSTRACT TRUNCATED AT 250 WORDS)
A five-year clinical experience with 112 Blalock-Taussig shunts.
In spite of recent advances in neonatal open repair for complex cyanotic heart disease, some patients require palliation with a systemic-to-pulmonary artery shunt. We report a 5-year experience (1985-1990) with 112 Blalock-Taussig shunts. Forty-six of the 92 patients had some variant of tetralogy of Fallot, with a wide spectrum of diagnoses in the remainder. The median age at surgery was 3 months. A classic Blalock-Taussig shunt was done in 26% (group I), and a 4- or 5-mm PTFE graft was utilized in the remainder (group II). The technical aspects of each of the procedures are reviewed. There were three early deaths in the entire group, none of them related to Blalock-Taussig shunt function. There was no incidence of early shunt insufficiency, bleeding, infection, limb ischemia, or pulmonary artery distortion. There was a 21% incidence of clinical congestive heart failure, seen somewhat more commonly in group I. The overall need for reshunting/open repair was similar in both groups, but there was a statistically longer interval between the initial Blalock-Taussig shunt and the second procedure in group I (21.6 vs 12.4 months). The Blalock-Taussig shunt remains a safe, reliable, and effective means of increasing pulmonary flow.
Use of a combined oxygen and carbon dioxide transcutaneous electrode in the estimation of gas exchange during exercise.
BACKGROUND: Accurate and reliable measurement of gas exchange during exercise has traditionally involved arterial cannulation. Non-invasive devices to estimate arterial oxygen (O2) and carbon dioxide (CO2) tensions are now available. A method has been devised and evaluated for measuring gas exchange during exercise with a combined transcutaneous O2 and CO2 electrode. METHODS: Symptom limited exercise tests were carried out in 24 patients reporting effort intolerance and breathlessness. Exercise testing was performed by bicycle ergometry with a specifically designed protocol involving gradual two minute workload increments. Arterial O2 and CO2 tensions were measured at rest and during exercise by direct blood sampling from an indwelling arterial cannula and a combined transcutaneous electrode heated to 45 degrees C. The transcutaneous system was calibrated against values obtained by direct arterial sampling before each test. RESULTS: In all tests the trend of gas exchange measured by the transcutaneous system was true to the trend measured from direct arterial sampling. In the 140 measurements the mean difference between the O2 tensions estimated by direct sampling and the transcutaneous method was 0.08 kPa (0.62 mm Hg, limits of agreement 4.42 and -3.38 mm Hg). The mean difference between the methods for CO2 was 0.02 kPa (0.22 mm Hg, limits of agreement 2.20 and -1.70 mm Hg). There was no morbidity associated with the use of the transcutaneous electrode heated to 45 degrees C. CONCLUSIONS: A combined transcutaneous O2 and CO2 electrode heated to 45 degrees C can be used to provide a reliable estimate of gas exchange during gradual incremental exercise in adults.
The cellular immune response to immunization with zona pellucida antigens.
The cellular immune response of mice to porcine and rat zona pellucida and cynomolgus macaques to porcine zona pellucida antigens was evaluated. Mice mounted a vigorous cellular response to both antigens, as determined by the T cell proliferation response in vitro. There was poor cross-reactivity to murine zonae by T cells or serum antibodies from mice immunized with rat zona pellucida. Nevertheless, ovaries from the mice immunized with rat zona had significantly fewer antral follicles than adjuvant-treated controls, suggesting that the immune response to the zona antigen disrupted follicular development. T cells from two macaques that had been immunized with porcine zona pelludica proteins proliferated in vitro in response to this antigen. Both macaques also had strong antibody responses. The patterns of urinary steroid metabolites in these animals provided clear evidence of ovarian malfunction following immunization. The data indicate that a significant cellular immune response is generated upon immunization of animals with zona pellucida antigens regardless of whether the antigens are cross reactive with the host zona antigens. Whether impaired ovarian function and follicular development are related to the cellular response must be determined in future studies.
Improving management of asthma: closing the loop or progressing along the audit spiral?
OBJECTIVE: To assess whether the management of asthma has improved from three consecutive surveys. DESIGN: Retrospective case note survey of acute asthma admissions in 1983 and 1989; case notes selected from 1985-6 survey of prospectively identified patients to include only patients with a final discharge code of asthma. SETTING: A large city teaching hospital. Patients--101 patients with acute asthma as the primary diagnosis in 1983; 85 in 1985-6; and 133 in 1989, 14 of whom were subsequently transferred elsewhere. MAIN MEASURES: Conformity with a checklist of important aspects of the process of asthma management including initial assessment, treatment, supervision, and discharge and review arrangements. RESULTS: All patient groups were similar in age, smoking habit, and stay in hospital and, as an objective guide to severity of asthma, had similar initial pulse rates. Major improvements occurred in management: by 1989, 119(90%) patients were treated with oral corticosteroids (69(68%), 67(79%) in 1983, 1985-6 respectively) and 109(82%) with oxygen (62(61%), 51(60%)) (both p < 0.001). 114(86%) had regular recording of peak flow measurements (53(52%), 54(64%); p < 0.001), and 103/119(86%) were discharged taking oral corticosteroids (66(65%), 63(74%); p < 0.01). Significantly fewer patients, however, had their regular inhaled corticosteroid treatment increased on discharge (38/119(32%) v 53(52%), 39(46%); p < 0.01), but more were receiving high dose inhaled treatment on admission. CONCLUSIONS: The management of asthma improved significantly, and the normal practice of doctors has changed in an area of practice with longstanding problems.
Dopamine clearance in critically ill infants and children: effect of age and organ system dysfunction.
To learn if there are age-related differences in the pharmacokinetic behavior of dopamine, plasma dopamine clearance was determined in 27 acutely ill infants and children who were receiving a continuous intravenous infusion of the drug. Steady-state clearance was calculated from dopamine concentration in arterial blood. Dopamine clearance was 60.7 +/- 28.1 ml/kg/min. The age of the patient exerted an effect on clearance of dopamine (r = -0.63; p less than 0.05), and dopamine clearance was nearly twice as rapid in children younger than 2 years as it was in older children (82.3 +/- 27.7 ml/kg/min versus 45.9 +/- 17.0 mg/kg/min). Conjugated bilirubin exerted an age-independent effect on clearance of dopamine; clearance was 44.8 +/- 28.6 ml/kg/min in children with abnormal conjugated bilirubin (greater than or equal to 0.9 mg/dl) and 70.1 +/- 2.56 ml/kg/min in children with normal conjugated bilirubin (less than 0.9 mg/dl). Clearance was lowest (29.8 +/- 5.7 ml/kg/min) in the four children who had both hepatic and renal dysfunction. Age is an important determinant of dopamine clearance, explaining in part the clinical observation that infants and young children require higher infusion rates.
Lung scanning for pulmonary embolism: clinical and pulmonary angiographic correlations.
A group of 78 patients with suspected pulmonary embolism was studied by both ventilation perfusion lung scanning and pulmonary angiography. Symptoms and clinical signs were analysed using Bayesian techniques to produce pre-test odds for pulmonary embolism in individual patients. While, as a group, those with embolism could be discriminated from those without on this basis, major overlap existed between the groups, invalidating the use of this approach for individual patients. Strict diagnostic criteria for interpretation of lung scans were accurate using pulmonary angiography as the 'gold standard', but at the expense of a significant number of patients (38 per cent) in the indeterminate (non-diagnostic) group. In the 48 patients in whom the test yielded a diagnostic result, there was a sensitivity of 100 per cent (15/15) and a specificity of 97 per cent (32/33). In the series as a whole, the likelihood of lung scanning correctly diagnosing pulmonary embolism was 55 per cent (15/27) and of correctly excluding embolism, 63 per cent (32/51). By the use of strict criteria for interpretation of lung scanning, reliable information can be obtained on the presence or absence of pulmonary embolism in a large proportion of patients suspected of having the condition. Such information is more discriminating than clinical signs and symptoms.
Diffuse meningeal thickening associated with pleural mesothelioma.
A case of pleural mesothelioma with diffuse spinal meningeal thickening as shown by magnetic resonance imaging is reported.