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Biomedical subjects

M E Hodson

Publications and source records attributed to M E Hodson.

At least 91 records · Page 5Linked to original sources
PubMed1995

DNase trials in cystic fibrosis.

Cystic fibrosis (CF) is a disease with a high morbidity and mortality from pulmonary disease. Sputum from CF patients contains high levels of deoxyribonucleic acid (DNA), which contribute to its viscoelasticity. Recombinant deoxyribonuclease (rhDNase) has been developed and in vitro studies have showed reduction in the viscoelasticity of CF sputum. This article reviews the in vivo clinical trials conducted to determine the safety and efficacy of this treatment. Phase 1 studies showed preliminary safety data and some evidence of clinical benefit. The two Phase 2 short-term studies showed improvement in pulmonary function and important safety data. The Phase 3 study, which included 968 patients, showed improvement in forced expiratory volume in one second (FEV1) of 5.8% and 5.6% in patients treated once and twice daily, respectively. The risk of developing an exacerbation of infection was reduced by 28% with once daily and 37% with twice daily treatment, compared to placebo. The drug was safe and there was some improvement in quality of life data. Longer-term open labelled studies, the results of intermittent administration, administration to severely ill patients, and the use of different delivery systems are reviewed. In conclusion, recombinant deoxyribonuclease is a new treatment which has been shown to benefit patients with cystic fibrosis when used in conjunction with conventional treatment.

Clinical Trials as Topic↗
PubMed1995

Inhalation of antibiotics in cystic fibrosis.

Aerosol administration of antipseudomonal antibiotics is commonly used in cystic fibrosis. However, its contribution to the improvement of lung function, infection and quality of life is not well-established. All articles published from 1965 until the present time concerning the inhalation of antibiotics in cystic fibrosis were collected by computerized literature search and analysed. Effective aerosol delivery is compromised by nebulizers with limited capacity to produce particles in the respirable range. Twelve studies concerning maintenance treatment were published. Four uncontrolled studies evaluating antibiotic aerosol maintenance treatment in stable patients indicated a beneficial effect in terms of reducing the number of hospital admissions. Eight placebo-controlled studies were found; six of these showed a significant improvement of lung function in the treatment group. Four studies showed a reduction of the number of hospital admissions. In some studies, there was a considerable negative effect of the nebulized placebo solution on the outcome, probably due to the improper choice of its osmolarity. Studies with antibiotic aerosols as adjunct to intravenous therapy in cystic fibrosis patients with an acute exacerbation showed no enhancement of the clinical effects of the intravenous antibiotic by the aerosol; sputum colony counts, however, were lower. Toxicity studies carried out so far have shown no renal or ototoxicity; however, long-term toxicity studies still have to be performed using higher dosages. Introduction or selection of resistant bacteria is relatively rare, but remains a matter of concern. Aerosol maintenance treatment with an appropriate antibiotic in high enough dosage can be recommended for patients with cystic fibrosis chronically infected with P. aeruginosa, and may improve lung function and reduce the number of hospital admissions due to an acute exacerbation.

Administration, Inhalation↗
PubMed1994

Cyclosporin pharmacokinetics in heart-lung transplant recipients with cystic fibrosis. Effects of pancreatic enzymes and ranitidine.

Cyclosporin (CsA) is currently the main immunosuppressive agent used in organ transplantation with considerable improvement in graft survival. Oral CsA solution is highly lipophilic, and its bioavailability may be reduced in cystic fibrosis (CF) heart-lung transplant recipients with pancreatic, gastrointestinal, and hepatic insufficiency. The bioavailability of oral CsA solution in 7 CF transplant recipients (5 male and 2 female with a mean age of 27 years and a mean weight of 49 kg) and 3 non-CF heart-lung recipients (1 male and 2 female with a mean age of 41 years and a mean weight of 60 kg) was studied. Following intravenous CsA administration, the kinetic curves were similar with no significant difference in the volume of distribution and clearance of CsA demonstrated between the CF and non-CF groups. The mean daily dose of oral CsA in 7 CF subjects (23.3 mg.kg-1) was significantly higher than the 3 non-CF heart-lung recipients (4.8 mg.kg-1). The mean maximum blood concentration of CsA for the oral dose was 776 ng.ml-1 for the 7 CF subjects, which was comparable with the mean peak values of 789 ng.ml-1 for the 3 non-CF control subjects. Poor enteral absorption of CsA probably accounts for the significantly lower mean bioavailability in the 7 CF subjects (14.9%) compared with the 3 non-CF control subjects (39.4%). The effects on the bioavailability of oral CsA solution by pancreatic enzymes (Creon) and histamine-2 antagonist (ranitidine) were also evaluated in the 7 CF subjects. No significant difference was demonstrated.

Administration, Oral↗
PubMed1994

The Flutter VRP1 as an adjunct to chest physiotherapy in cystic fibrosis.

The Flutter VRP1 (Flutter) is claimed to increase the clearance of excess bronchial secretions and to improve lung function and oxygenation, but these claims were based on computer models, laboratory assisted experiments and uncontrolled clinical trials. A prospective randomized clinical trial was undertaken, in subjects with cystic fibrosis, using the active cycle of breathing techniques as the 'gold standard'. The claims could not be substantiated and the possibility of sputum retention was of concern when the Flutter was used as significantly more sputum (P < 0.001) was cleared with the active cycle of breathing techniques alone. There were no significant changes in lung function or oxygenation.

Adult↗
PubMed1994

Hospital care for adults with cystic fibrosis: an overview and comparison between special cystic fibrosis clinics and general clinics using a patient questionnaire.

BACKGROUND: Provision of medical care for adult patients with cystic fibrosis is an increasing problem as the number of patients surviving into adulthood increases. Recent reports have suggested that care is best provided in specialist centres because of longer survival. Recent changes in the National Health Service funding and delivery of service may adversely affect the provision of such a specialist service. The aim of this study was to assess the current pattern of medical service received by adults with cystic fibrosis and to compare the type of care between special cystic fibrosis and general clinics. METHODS: Confidential postal questionnaires were sent to all 1052 members of the Association of Cystic Fibrosis Adults (ACFA) comprising 59% of the UK population of cystic fibrosis patients over 15 years and 80% over 25 years of age. The response rate was 82%. RESULTS: Two thirds of patients were attending special cystic fibrosis clinics for either adults or adults and children. There were significant differences in the proportion of patients using special cystic fibrosis clinics between regions but not between social class groups. Significant differences between cystic fibrosis and general clinics were noted. Patients attending cystic fibrosis clinics were more likely to have had simple clinical investigations (blood tests, sputum culture, oxygen saturation, chest radiography, weight and lung function measurement) in the previous year. They were also more likely to have received intravenous antibiotics at home, and to have access to paramedical personnel. Patients attending cystic fibrosis clinics were taking higher doses of pancreatic enzyme supplements with respect to quantity and potency of preparation. Such patients also had less severe symptoms irrespective of social class, and were more likely to be satisfied with professional aspects of their care. Regardless of type of clinic, potential deficiencies were identified in overall medical care with omission of clinical investigations in severely affected patients and evidence of undertreated respiratory and digestive symptoms in patients with moderate and severe disease. CONCLUSIONS: This survey provides evidence that adults with cystic fibrosis attending special cystic fibrosis clinics receive more intensive care, have better symptom control, and are more satisfied with the service provided than those attending general clinics.

Adolescent↗
PubMed1993

Demographic and social characteristics of adults with cystic fibrosis in the United Kingdom.

OBJECTIVE: To obtain information about social and demographic characteristics and lifestyle of adult patients with cystic fibrosis, including those who do not attend major specialist clinics. DESIGN: Confidential self completion postal questionnaire to adult patients with cystic fibrosis, asking about social and demographic characteristics, social class and occupation, employment, education, insurance and social security benefits, symptom severity, and medical care. SETTING: National association for adults with cystic fibrosis. SUBJECTS: 1052 adult members of the Association of Cystic Fibrosis Adults UK, accounting for 68% of those with cystic fibrosis in the United Kingdom population over 16 years of age and over 80% of those over 25 in June 1990. RESULTS: The response rate was 82% (397 women, 423 men). Most adults with cystic fibrosis were found to be living fulfilling lives into adulthood. Significantly fewer men were married or cohabiting than women (110 (26%) men, 175 (44%) women). 420 (55%) responders were working, and of these 235 (56%) had less than two weeks' sick leave a year. Half of those not employed gave ill health as the reason. Revealing that they had cystic fibrosis at job interviews reduced likelihood of being employed for those with mild to moderate disease. People with cystic fibrosis had been less successful than the general population in achieving O level or equivalent qualifications, but more successful in achieving A level or higher qualifications. Achievement of any qualifications enhanced employment prospects irrespective of disease severity. CONCLUSION: Contrary to an image of chronic ill health and disability, a high proportion of adults with cystic fibrosis are living full and productive lives.

Adolescent↗
PubMed1993

Cystic fibrosis: antibiotic prescribing practices in the United Kingdom and Eire.

The antimicrobial prescribing practices of 26 physicians from the U.K. and Eire who care for patients with cystic fibrosis (CF) were assessed by postal questionnaire. Our main aim was to delineate divergent practices which may reveal a need for controlled prospective studies. For first-line intravenous (i.v.) therapy of acute exacerbations associated with Pseudomonas aeruginosa, 20 physicians (76.9%) combine a penicillin derivative with an aminoglycoside, in contrast to five (19.2%) who regularly use i.v. monotherapy with ceftazidime and one who combines i.v. ceftazidime with an aminoglycoside. When i.v. therapy is considered inappropriate, oral ciprofloxacin is sometimes used by all clinicians and oral broad spectrum agents are used in addition by 13, chloramphenicol being prescribed most often. Excluding allergy, the most important factor influencing choice of agents by 19 (73.1%) physicians is the most recent sputum susceptibility results. For maintenance therapy, 21 prescribe oral anti-staphylococcal agents if Staphylococcus aureus is isolated; of these, eight do so only if lung function deteriorates, nine after repeated isolation and four after first isolation of S. aureus. The remaining five physicians give anti-staphylococcal drugs to all patients once the diagnosis of CF is made. For maintenance of lung function in patients with persistent P. aeruginosa, all physicians used nebulized antibiotics, the indications for which vary between units. There was general concordance in the therapy of exacerbations associated with P. aeruginosa, whereas the use of agents to maintain lung function is more varied. We suggest that prospective studies address practices which vary greatly, such as the route, the duration and the timing of initiating antibiotic therapy given to maintain lung function.

Administration, Inhalation↗
PubMed1993

Pseudomonas cepacia: pulmonary infection in patients with cystic fibrosis.

This retrospective study reviews the patterns of P. cepacia pulmonary infection in 75 of a total of 872 mainly adults with cystic fibrosis, registered here during the 4 years 1987-1990; 35 (47%) were female. During this period, 55 patients acquired P. cepacia and the annual incidence and prevalence rates have remained between 1.6 and 3.1%, and 4.1 and 5.9%, respectively. The mean age at the time of the first isolation of P. cepacia was 23 years, ranging 11-45 years. Sixty-eight percent of the initial isolates were multi-resistant (sensitive to fewer than three of 15 anti-pseudomonal agents). Prior to acquisition of P. cepacia, 28 (50.9%) patients already had severe lung disease and only three had normal lung function. Infection was transient in 39.1% of patients. Initial multi-resistance of P. cepacia to anti-pseudomonal agents was significantly associated with persistent infection. Clinical outcome was unaffected by age, sex and early intravenous antibiotic therapy but was significantly adversely affected by increasing severity of lung disease at the onset of P. cepacia infection and by initial multi-resistance, and persistence of the organism. Thus, all patients with normal or mild lung disease at the outset of infection have remained clinically stable, whereas, only six of 28 patients with severe disease remained stable, three of whom were transiently infected with P. cepacia. The prevalence of P. cepacia at the time of death fluctuated between 12.5% and 26.9% during the study period.

Adolescent↗
PubMed1993

Regular three monthly oral ciprofloxacin in adult cystic fibrosis patients infected with Pseudomonas aeruginosa.

In 31 adult patients with cystic fibrosis (CF) who were chronically infected with Pseudomonas aeruginosa we examined the effect of giving regular three monthly oral ciprofloxacin. Patients received ciprofloxacin or placebo for 10 days every 3 months for 1 yr in a randomized, double-blind, placebo-controlled study. During each course of treatment patients receiving ciprofloxacin reported an improvement in cough, sputum production and peak expiratory flow (PEF) P = < 0.005. During the year of study patients receiving ciprofloxacin showed an improvement in PEF when compared with those receiving placebo (P = < 0.05) but the changes in FEV1 and FVC were not statistically different in either group. Regular oral ciprofloxacin was well tolerated but did not prevent hospital admissions or reduce the number of courses of intravenous antibiotics throughout the year. The median MIC to ciprofloxacin in the active treatment group rose from 0.5 mg l-1 to 0.75 mg l-1 during treatment. We conclude that CF patients are likely to benefit from oral ciprofloxacin for exacerbations of respiratory symptoms. However, regular treatment with ciprofloxacin over 1 yr improves PEF but does not reduce the rate of hospital admissions with acute exacerbations of respiratory symptoms.

Administration, Oral↗
PubMed1993

A cohort study of cystic fibrosis and malignancy.

A cohort of 412 patients first attending a cystic fibrosis (CF) clinic between 1961 and 1989 were followed up to 30 June 1989. The number of malignancies observed in the cohort was compared with the number expected based on the age, sex and calendar-year-specific cancer registration rates for England and Wales. Four CF patients were diagnosed as having malignancies before 30 June 1989. The tumours were: adenocarcinoma of the terminal ileum; adenocarcinoma of the pancreas, testicular teratoma, and B-cell lymphoma. This compares with 0.89 malignancies expected on the basis of rates in England and Wales (Standardised Registration Ratio = 452; 95% confidence interval 122-1150, P = 0.03). The single case of adenocarcinoma of the terminal ileum contrasts with less than 0.001 expected (P = 0.003) and that of the pancreas with 0.007 expected (P = 0.01). A further adenocarcinoma of the pancreas was diagnosed 2 years after the end of the study period. The two cases of pancreatic cancer compare with 0.008 expected (P = 0.0001) during the period to mid 1991. On the basis of the present findings and previous case reports in the literature adenocarcinoma of the pancreas and adenocarcinoma of the terminal ileum may be associated with cystic fibrosis.

Adenocarcinoma↗
PubMed1993

Nasal epithelial ion transport and genetic analysis of infertile men with congenital bilateral absence of the vas deferens.

It has been suggested that congenital bilateral absence of the vas deferens (CBAVD), an important cause of male infertility, is a variant of cystic fibrosis (CF). This study describes a defect in chloride conductance across the nasal epithelium of subjects with CBAVD which is dissimilar to that found in patients with CF. It also demonstrates normal sodium transport across the nasal epithelium in these men, in contrast to patients with CF who exhibit increased sodium absorption. The increased frequency of CFTR mutations in these men implicates the CFTR gene in the pathogenesis of this disorder. Genetic analysis of men with CBAVD who were heterozygous for a known CFTR mutation failed to identify a second mutation within any of the exons or introns of the CFTR gene. These results demonstrate that most men presenting with CBAVD are not compound heterozygotes for mutations within the CFTR gene and can be distinguished from individuals with atypical or asymptomatic CF on the basis of the bioelectric properties of their nasal epithelium. We postulate that mutations in the promoter region or at other regulatory sites of the CFTR gene may be responsible for the CBAVD phenotype in a proportion of cases.

Biological Transport↗
PubMed1993

Adult cystic fibrosis: association of acute pulmonary exacerbations and increasing severity of lung disease with auxotrophic mutants of Pseudomonas aeruginosa.

BACKGROUND: Pseudomonas aeruginosa has been located in the endobronchiolar spaces of patients with cystic fibrosis where nutrients may be limited. In these sites it is thought that adaptation of the pathogen might occur and growth factors, present in relative excess, may thus promote survival of the organism. Auxotrophy of pulmonary isolates of P aeruginosa has previously been shown to be a feature of cystic fibrosis and chronic lung sepsis; auxotrophic isolates have additional nutritional requirements to the prototrophic "wild types" of the species. A study was therefore carried out to determine whether the proportion of auxotrophs differs between stable and acutely ill patients, or correlates with the extent of underlying disease. METHODS: Sputum samples were cultured for P aeruginosa and tested for auxotrophy by spreading serial dilutions of homogenised sputum on to a minimal medium which supports only prototrophs, and a complete medium which supports both nutritional types. The proportion of auxotrophs to prototrophs was determined and growth factors of confirmed auxotrophs were identified. RESULTS: Thirty two (86%) of 37 adults with cystic fibrosis infected with P aeruginosa harboured auxotrophs; methionine dependent mutants were isolated from seven of 16 patients tested (44%). More than 50% of the total number of colonies were auxotrophic in 19 of 26 samples (73%) from patients with acute exacerbations and in only six of 15 samples (40%) from clinically stable patients. In four patients from whom samples in both the acute and stable states were available, the proportion of auxotrophs fell in the sample taken when stable. Auxotrophs predominated in all samples from 11 of those patients with very severe underlying lung disease, in contrast to 13 of 30 samples from patients with less severe disease. There was no association between the percentage of auxotrophs and the presence of other respiratory pathogens. CONCLUSIONS: The majority of adults with cystic fibrosis infected with P aeruginosa harbour auxotrophs in the sputum. A significant proportion of acutely ill patients and those with severe underlying disease have a preponderance of auxotrophs in the sputum compared with stable patients and those with less severe disease.

Acute Disease↗
PubMed1993

In vitro bioelectric properties of bronchial epithelium from transplanted lungs in recipients with cystic fibrosis.

BACKGROUND--Bronchial epithelial function after heart-lung transplantation (HLT) for cystic fibrosis (CF) may be affected by the original disease as well as other factors such as prolonged organ ischaemic time, the interruption of bronchial arterial and lymphatic supply, infection, rejection, and cyclosporin. In vitro measurement of the bioelectric properties of the bronchial mucosal lining may be an effective means of characterising the mucosal function of the lung allografts in response to pharmacological agents. METHODS--Bronchial mucosal tissues from explanted native lungs of CF and non-CF patients at transplantation were used to assess the possible application of a mini-Ussing chamber. With this technique, the bioelectric responses of bronchial mucosal biopsies from six patients with CF, one patient with congenital heart disease, four with primary pulmonary hypertension, and one with emphysema, all after HLT, were studied. The bioelectric and pharmacological responses of biopsies of bronchial mucosa from patients after HLT were compared with biopsies from non-CF non-HLT subjects. RESULTS--The altered bioelectric properties of CF tissues could be detected by the mini-Ussing chamber technique. The basal bioelectric values and the responses to amiloride and isoprenaline in CF patients were not different from those in non-CF patients two years after HLT. No significant difference in the basal bioelectric properties and responses to amiloride and isoprenaline was found between HLT recipients and non-CF non-HLT subjects. CONCLUSIONS--The mini-Ussing chamber is an effective means of characterising the typical CF bioelectric defect which was not found in the transplanted lungs of CF patients up to two years after HLT. Furthermore, values were unaltered in comparison with non-transplanted lungs, suggesting that bronchial epithelial function is maintained after HLT.

Adolescent↗
PubMed1993

Cystic fibrosis: the disease.

Cystic fibrosis is an inherited disease affecting mainly the Caucasian population. In recent years there have been major advances in understanding the genetics and pathophysiology of the disease. Cystic fibrosis affects many organs, but predominantly the respiratory system and alimentary tract. Current treatment including chest physiotherapy, antibiotics, good nutrition and enzyme therapy, together with the complications of the disease are described. Even with the best modern treatment there is still a significant morbidity and mortality. New advances in treatment, which offer hope for the future, are explored.

Cystic Fibrosis↗
PubMed1993

No added benefit from nebulized amiloride in patients with cystic fibrosis.

In cystic fibrosis (CF) airway epithelial sodium absorption is increased 2-3 fold. Since sodium absorption is inhibited by the sodium channel blocker amiloride, our aim was to assess its therapeutic benefit in cystic fibrosis. A randomized, double-blind, placebo-controlled, cross-over trial of nebulized amiloride was performed in 23 patients with cystic fibrosis. Amiloride or placebo was administered four times daily for two six month periods. Existing treatment was continued, and any infective exacerbations treated in the usual way. Fourteen patients completed the study. No significant changes occurred in forced expiratory volume in one second, forced vital capacity, oxygen saturation, body weight, sputum volume, culture and rheology, serum urea, and electrolytes, white cell count and erythrocyte sedimentation rate during either treatment period. The frequency of infective exacerbations was also not different in either treatment period. We were thus unable to confirm the benefit shown in the only other clinical trial of nebulized amiloride in cystic fibrosis and conclude that, in the presence of established treatment for cystic fibrosis lung disease, nebulized amiloride offers no additional clinical benefit.

Administration, Intranasal↗
PubMed1993

The medical management of patients with cystic fibrosis following heart-lung transplantation.

Transplantation for end-stage respiratory failure in cystic fibrosis (CF), with encouraging medium-term results, is now possible. This paper details the postoperative medical treatment required by these patients. The management of 79 patients who underwent heart-lung transplantation is described. Details of intensive care, postoperative care, long-term follow-up, and the problems specific for cystic fibrosis patients are reported. The duration of care in the Intensive Care Unit (ICU) was 1-93 days (median 5 days). Intubation was required for 7 h to 93 days (median 48 h), and 11 patients required haemodiafiltration. High doses of cyclosporin A (mean 22 mg.kg-1 q.d.) were required. Acute rejection was common. There were 133 episodes of infection: bacterial 115, viral 11, and other organisms 7. Grand mal seizures occurred in 10 patients, lymphoproliferative disorders in 4, and obliterative bronchiolitis in 17. The median duration of hospital stay was 32 days. Despite having a multi-system disease, patients with CF can be successfully transplanted, if detailed attention is paid to their complex medical management.

Adult↗