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Biomedical subjects

D G Peckham

Publications and source records attributed to D G Peckham.

15 recordsLinked to original sources

Measurement of urinary N-acetyl-b-D-glucosaminidase in adult patients with cystic fibrosis: before, during and after treatment with intravenous antibiotics.

BACKGROUND: Patients with cystic fibrosis (CF) are at high risk from the nephrotoxic effects of intravenous antibiotics due to repeated and prolonged courses of therapy. Routine methods of monitoring renal injury are insensitive. N-acetyl-b-d-glucosaminidase (NAG) is a lysosomal enzyme present in the renal proximal tubular cells, with increased excretion an indicator of renal tubular dysfunction. METHODS: Urinary NAG, creatinine, serum creatinine, electrolytes and BUN were measured on days 1, 14 and at the first out-patient visit following treatment with tobramycin or colistin. Urinary NAG levels were corrected for urinary creatinine and expressed as a NAG ratio. Patients who received>1 course of intravenous antibiotics during the study period were included in a separate analysis of the cumulative effect of treatment. RESULTS: 88 patients (44 female, 31 with CFRD) completed a single course of intravenous antibiotics. 71 patients had urinary NAG levels at follow-up. The median time to follow-up was 50 days. Serum electrolytes, creatinine and BUN were normal throughout. A 3.5-fold increase in urinary NAG excretion was observed between day 1 and 14 and 46% of patients had an elevated NAG level at follow-up. A highly significant difference in NAG excretion was observed on day 14 for tobramycin vs. colistin (median 2.24 vs. 0.98, p<0.001). A significant difference in NAG excretion was seen in patients with CFRD at all measured time points. Patients with CFRD had a significantly worse clinical status and had received more days of intravenous antibiotics over the previous 6 years. In 20 (80%) of 25 patients who received>1 course of treatment during the study period, baseline NAG levels were significantly higher in subsequent courses (p<0.001). There was a significant correlation between previous exposure to colistin and baseline NAG levels (r=0.389, p<0.001). CONCLUSIONS: Both tobramycin and colistin cause acute renal tubular injury with a significant rise in urinary NAG excretion. Patients with CFRD seem to be at greatest risk of renal tubular damage. Cumulative damage is evident with repeated dosing. Previous exposure to nephrotoxic antibiotics, especially colistin, is associated with elevated baseline NAG levels. We recommend that colistin is reserved for patients with resistant Pseudomonas aeruginosa or those who are intolerant to tobramycin. Serial longitudinal NAG measurements may be useful in patients with CF, especially those with CFRD, to identify patients at risk of developing renal disease.

Acetylglucosaminidase↗

Dietary intakes in adult patients with cystic fibrosis--do they achieve guidelines?

BACKGROUND: Most patients with cystic fibrosis (CF) require a higher energy and protein intake than their healthy peer group. There are few data on dietary intakes of adult patients. The aim of this study was to determine nutritional intakes in an adult population with CF. The impact of nutritional intervention and disease on macronutrient intake was examined. METHODS: Retrospective cross-sectional analysis of 94 unweighed food diaries at annual review (1995-2000). Energy and protein intakes were compared to the estimated average requirement (EAR) for energy and reference nutrient intake (RNI) for protein. The effect of diet alone, oral supplements, enteral tube feeding, and cystic fibrosis related diabetes (CFRD), on macronutrient intake was examined and impact of pancreatic sufficency (PS) and lung transplantation. RESULTS: Mean energy and protein intakes approached recommended CF guidelines, but in 72% of assessments these values were not achieved. Mean energy and protein intakes for patients on diet alone and protein intake for those with CFRD failed to meet recommendations. Oral supplementation and enteral tube feeding regimens increased energy and protein intake above recommended levels. No group achieved 40% total energy from fat. Patients receiving enteral tube feeds had the highest mean energy and protein intakes but lowest body mass index (BMI) and lung function. CONCLUSION: Adequate mean energy and protein intakes in adult patients with CF mask subgroups of patients who fail to meet recommendations ie. diet alone, diabetic. Oral supplementation and enteral tube feeding increase energy and protein intake but fail to achieve an adequate BMI level in subjects with a decreased clinical status. Individual nutritional assessment remains essential.

Adolescent↗

Treatment of resistant distal intestinal obstruction syndrome with a modified antegrade continence enema procedure.

We report a case of a patient with CF who had a long history of recurrent distal intestinal obstruction syndrome. She had been treated with conventional treatment including gastrografin, n-acetyl cysteine, Klean prep and Picolax. She underwent a modified antegrade continence enema procedure. She currently irrigates her conduit every 2-3 days. She has had no further symptoms of distal intestinal obstruction syndrome.

Adolescent↗

Effect of oral bisphosphonates on bone mineral density and body composition in adult patients with cystic fibrosis: a pilot study.

BACKGROUND: Approximately two thirds of adult patients with cystic fibrosis have reduced bone mineral density and up to one quarter have osteoporosis at one or more sites. Any bone mineral deficits are likely to be exacerbated in patients following lung transplantation by their immunosuppressive regimen. Vertebral collapse and rib fractures will impair the ability to cough and the efficacy of physiotherapy treatments. METHODS: Patients attending the Leeds Regional Adult Cystic Fibrosis Unit with either osteopenia or osteoporosis on dual energy x ray absorptiometry (DXA) scanning were offered treatment with oral bisphosphonates after exclusion of abnormal vitamin D, calcium, or phosphate levels, abnormal thyroid function, or hypogonadism. Those declining treatment or patients with a normal initial DXA scan formed the control group. A second DXA scan was performed after a mean of 2.4 years in the treatment group and 2.9 years in the non-treatment group. Patients in the active group were asked to complete a short questionnaire detailing their adherence to treatment. RESULTS: The medians of the differences in annual changes in bone parameters between treatment and control groups showed significant differences in bone mineralisation in favour of the treatment group at the lumbar spine (L2-L4), the femoral neck, and for total body measurements. There were no significant differences in weight, height, or body composition in either patient group. Most treated patients stated that they adhered to treatment most of the time. CONCLUSION: Treatment with oral bisphosphonates may improve bone mineralisation in adult patients with cystic fibrosis. The results of this pilot study need to be further explored in a randomised controlled trial.

Absorptiometry, Photon↗

Antibiotic treatment of multidrug-resistant organisms in cystic fibrosis.

Respiratory tract infection with eventual respiratory failure is the major cause of morbidity and mortality in cystic fibrosis (CF). Infective exacerbations need to be treated promptly and effectively to minimize potentially accelerated attrition of lung function. The choice of antibiotic depends on in vitro sensitivity patterns. However, physicians treating patients with CF are increasingly faced with infection with multidrug-resistant isolates of Pseudomonas aeruginosa. In addition, innately resistant organisms such as Burkholderia cepacia complex, Stenotrophomonas maltophilia and Achromobacter (Alcaligenes) xylosoxidans are becoming more prevalent. Infection with methicillin-resistant Staphylococcus aureus (MRSA) is also a problem. These changing patterns probably result from greater patient longevity and increased antibiotic use for acute exacerbations and maintenance care. Multidrug-resistant P. aeruginosa infection may be treated successfully by using two antibiotics with different mechanisms of action. In practice antibiotic choices have usually been made on a best-guess basis, but recent research suggests that more directed therapy can be achieved through the application of multiple-combination bactericidal testing (MCBT). Aerosol delivery of tobramycin for inhalation solution achieves high endobronchial concentrations that may overcome bacterial resistance as defined by standard laboratory protocols. Resistance to colistin is rare and this antibiotic should be seen as a valuable second-line drug to be reserved for multidrug-resistant P. aeruginosa. The efficacy of new antibiotic groups such as the macrolides needs to be evaluated.CF units should adopt strict segregation policies to interrupt person-to-person spread of B. cepacia complex. Treatment of panresistant strains is difficult and often arbitrary. Combination antibiotic therapy is recommended, usually tobramycin and high-dose meropenem and/or ceftazidime, but the choice of treatment regimen should always be guided by the clinical response.The clinical significance of S. maltophilia, A. xylosoxidans and MRSA infection in CF lung disease remains uncertain. If patients show clinical decline and are chronically colonized/infected with either of the former two pathogens, treatment is recommended but efficacy data are lacking. There are defined microbiological reasons for attempting eradication of MRSA but there are no proven deleterious effects of this infection on lung function in patients with CF. Various treatment protocols exist but none has been subject to a randomized, controlled trial. Multidrug-resistant microorganisms are an important and growing issue in the care of patients with CF. Each patient infected with such strains should be assessed individually and antibiotic treatment planned according to in vitro sensitivity, patient drug tolerance, and results of in vitro studies which may direct the physician to antibiotic combinations most likely to succeed.

Anti-Bacterial Agents↗

Stenotrophomonas maltophilia contamination of nebulizers used to deliver aerosolized therapy to inpatients with cystic fibrosis.

There is circumstantial evidence that nebulizer equipment may be a source of Stenotrophomonas maltophilia for patients with cystic fibrosis. Eighty-nine inpatient nebulizers were examined for evidence of S. maltophilia contamination of which nine (10%) yielded 14 strains of the bacterium. Environmental samples were obtained from 73 different sites on the ward, of which 17 (23%) yielded a further 21 strains. Positive sites included taps, sink drains, and potable water. Genotyping using ERIC-PCR and pulsed-field gel electrophoresis revealed that two pairs of patients' nebulizers were contaminated with closely related strains. None of the S. maltophilia isolates obtained from the ward environment shared genotypes with those obtained from the nebulizers. The frequency of isolation of S. maltophilia from potable water sources on the ward suggests that contamination may result from using it to clean reusable nebulizer equipment, particularly if this is followed by inadequate drying. Although the actual source of S. maltophilia contamination of hospital-use nebulizer equipment in this study remained elusive, these results have important infection control implications.

Adolescent↗

A pilot study of zafirlukast as an anti-inflammatory agent in the treatment of adults with cystic fibrosis.

BACKGROUND: Persistent endobronchial inflammation is in part responsible for the attrition of lung function seen in cystic fibrosis. Leukotrienes act as pro-inflammatory mediators. The aim of this study was to assess the efficacy of the leukotriene receptor antagonist zafirlukast as a potential anti-inflammatory agent in the treatment of adult patients with cystic fibrosis. METHODS: Clinically stable patients were enrolled in the study if they had no history or clinical evidence of asthma, bronchial hyper-reactivity, or aspergillosis. They were randomised to receive zafirlukast 20 mg twice daily with all routine treatment for four months or routine treatment alone in an open cross-over design. Primary endpoints were changes in respiratory function tests and a modified NIH clinical score. RESULTS: Thirty patients were enrolled and 25 completed. There was a significant improvement in the modified NIH clinical score but no significant increase in respiratory function with zafirlukast. CONCLUSIONS: Patients receiving a leukotriene receptor antagonist in addition to routine treatments showed significant improvement in a clinical score which is a composite of clinical wellbeing, chest radiograph appearance, and physical examination. Respiratory function showed a non-significant trend towards improvement with treatment. Zafirlukast may benefit patients with CF. An adequately powered study is justified on the basis of these results.

Adult↗

Improvement in patient compliance with long-term oxygen therapy following formal assessment with training.

In the Department of Respiratory Medicine, North Staffordshire Hospital, patients fulfilling the Department of Health criteria for long-term oxygen therapy (LTOT) attend a practical teaching session on the use of their oxygen concentrator before commencing therapy. In the present study, we have audited the prescribing of LTOT in all patients in three health districts in the North West Midlands reviewed between June 1992 and July 1994. They were split into two groups. The first had the assessment and training programme in the department. Patients in the control group had been prescribed LTOT from outside the department without any formal training. In both groups of patients information was collated 6 months after starting LTOT by means of a questionnaire assessing patients', understanding of both their need for oxygen and their disease process, the dangers of oxygen therapy and present smoking habit. Objective information about the usage of each concentrator was obtained from engineer reports. Thirty-six patients (eight from the trained group and 28 controls) died before evaluation at 6 months. Forty-five patients (29 male, mean age 71 years) received training and 41 control patients (24 male, mean age 72 years) were evaluated. Thirty-seven (82%) patients who had received formal training were using their concentrator for greater than 15 h compared with only 18 (44%) of the controls (P = 0.0002). Forty-two (93%) patients who had received training understood why they were using LTOT compared with only 17 (41%) in the control group (P = 0.00001). Although both groups had a similar understanding of the dangers of smoking while on oxygen therapy, six (15%) of the control group were smoking as compared to only one (2%) of the trained group (P = 0.038). One of the control patients had received significant facial burns as a direct result of smoking while on oxygen. Further efforts are required to ensure that all patients prescribed LTOT should have a formal respiratory assessment as well as training to improve compliance and to obtain maximal benefits from such therapy.

Aged↗

Sarcoidosis.

Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology. The condition commonly affects young adults and frequently presents with bilateral hilar lymphadenopathy with or without pulmonary infiltration, ocular or cutaneous lesions. The clinical presentation can be extremely varied depending upon the organs affected. The diagnosis is firmly established when recognised clinical and radiographic findings are supported by histological evidence of discrete non-necrotising epithelioid cell granulomata in one or more organs. Sarcoidosis is usually self-limiting with spontaneous resolution, although in a few patients there is a progressive downhill course, culminating in irreversible fibrosis and severe impairment of organ function.

Adult↗

Effect of oral digoxin, topical ouabain and salbutamol on transepithelial nasal potential difference in patients with cystic fibrosis.

1. Airway epithelium in cystic fibrosis is characterized by a defect in chloride secretion across the apical membrane and an increase in sodium absorption. The increased rate of sodium absorption can be inhibited in vitro by ouabain, a Na(+)-K(+)-ATPase inhibitor, and in cystic fibrosis patients the number and activity of nasal epithelial Na(+)-K(+)-ATPase pumps is increased. 2. We have performed a series of studies to determine whether drugs which modify airway epithelial Na(+)-K(+)-ATPase activity in vitro can modify nasal potential in cystic fibrosis patients in vivo. As transepithelial nasal potential difference measurements were used to study the effect of drug modulation of airway epithelial ion transport in vivo, the repeatability of the technique was first evaluated. In order to assess the effectiveness of the technique used for measuring nasal potential difference, a pilot study was carried out using topical amiloride, a drug which has previously been shown to inhibit airway epithelium sodium transport in vivo. We then studied the effects of ouabain and digoxin, two inhibitors of Na(+)-K(+)-ATPase, on nasal potential difference. 3. In study 1, nasal potential difference measurements were repeated on non-consecutive days in 20 patients with cystic fibrosis and 20 healthy individuals. Healthy subjects had a mean (SEM) potential difference value of -19.5 (0.9) mV with a 95% range for a single estimate of 75-133%. In patients with cystic fibrosis, the mean (SEM) potential difference was -40.4, (2.1) mV, with a 95% range for a single estimate of 74-136%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effect of addition of exercise to chest physiotherapy on sputum expectoration and lung function in adults with cystic fibrosis.

Promotion of sputum expectoration by chest physiotherapy is an essential part of cystic fibrosis management. The role of exercise in improving sputum expectoration and lung function in these patients is more contentious. We therefore investigated the effect of adding an exercise programme to conventional chest physiotherapy in eight adult subjects (four male) with cystic fibrosis. Subjects were treated on two non-consecutive days of the second week of a course of in-patient antibiotic therapy in a cross-over fashion. On the exercise and physiotherapy day, subjects exercised 60 min before physiotherapy. On the physiotherapy alone day, subjects rested for 60 min instead of exercising. Physiotherapy was administered on both study days (postural drainage, percussion, deep breathing, vibrations, forced expiratory technique and coughing). Lung function tests were performed at baseline, after exercise or rest and again immediately and 30 min after physiotherapy. Sputum weights were measured in the 60 min of exercise or rest (period A) and for the 60 min physiotherapy period and 30 min after physiotherapy (period B). Mean total sputum expectoration (period A and B) was 14 g on physiotherapy alone and 21.5 g (4.8) on exercise and physiotherapy (mean difference 7.5 g, 95% CI 1.4-13.6 g, P = 0.02). Mean sputum weights during period A (i.e. rest vs. exercise) on physiotherapy alone and exercise and physiotherapy were 2.6 and 7 g respectively (mean difference 4.4 g, 95% CI-0.07-8.8 g, P = 0.053).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗