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Biomedical subjects

P Noone

Publications and source records attributed to P Noone.

At least 19 recordsLinked to original sources

Sodium channel blockers for cystic fibrosis.

BACKGROUND: People with cystic fibrosis (CF) have increased transport of the salt, sodium across their airway lining. Over-absorption of sodium results in the dehydration of the liquid that lines the airway surface and is a primary defect in people with CF. OBJECTIVES: To determine whether the topical administration of drugs that block sodium transport improves the respiratory condition of people with CF. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. We contacted principal investigators known to work in the field, previous authors and pharmaceutical companies who manufacture ion transport agents for unpublished or follow-up data. Most recent search of the Group's register: March 2006 SELECTION CRITERIA: Published or unpublished randomised controlled trials (RCTs) or quasi-randomised controlled trials of sodium channel blockers compared to placebo or another sodium channel blocker or the same sodium channel blocker at a different dosing regimen. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data. Meta-analysis was limited due to differing study designs. MAIN RESULTS: Four RCTs, with a total of 205 participants, examining the topical administration of the short-acting sodium channel blocker, amiloride, compared to placebo were identified as eligible for inclusion in the review. For three studies, interventions for six months were completed and it was possible to calculate relative change in respiratory function (FVC). There was a significant difference found in relative change in FVC in favour of placebo (GIV analysis of weighted mean difference for FVC; 1.51% (95% confidence interval -2.77 to -0.25). There were no significant differences identified in other clinically relevant outcomes. AUTHORS' CONCLUSIONS: We found no evidence that the topical administration of a short-acting sodium channel blocker improves respiratory condition in people with cystic fibrosis and some limited evidence of deterioration in lung function.

Cystic Fibrosis↗

Bronchiolitis obliterans organizing pneumonia in a patient with non-Hodgkin's lymphoma following R-CHOP and pegylated filgrastim.

Bronchiolitis obliterans organizing pneumonia (BOOP) presents with fever, dyspnoea, pleuritic chest pain and hypoxia. The diagnosis can be made from radiological appearances on chest radiograph and CT scan correlated with histological findings following biopsy. We present a 52-year-old gentleman undergoing treatment for high grade non-Hodgkin's lymphoma who developed respiratory symptoms during chemotherapy. BOOP was diagnosed and he responded well to oral prednisolone. The cause of BOOP is often not certain. However, in this case we suspect pegylated filgrastim or rituximab as possible agents.

Antibodies, Monoclonal↗

An audit of NHS Trust alcohol policy referrals to an occupational health service.

An exploratory review of 33 referrals to an Occupational Health Service of employees with alcohol problems provided information on age and sex, job category, mode of referral, medical and social problems and outcome. Case records were examined providing information on clinical assessment and the treatment options. The high rates of relapse, drop-out and refusal of help, supported the view that this population had serious alcohol problems. Clinical recording by occupational physicians showed a marked variability. No doctors were included in the sample although this group is known to be vulnerable. Blood testing was used infrequently. Occupational health clinical practice could be enhanced by the use of clinical protocols, systems of morbidity recording and co-operative studies with other agencies. Further prospective studies are needed.

Adult↗

Pharmacologic modulation of salt and water in the airway epithelium in cystic fibrosis.

Cystic fibrosis (CF) is a recessive genetic disease with thickened airway secretions that result from abnormal airway epithelial ion transport, including defective cyclic AMP-mediated Cl- (liquid) secretion and excessive Na+ (liquid) absorption. These abnormalities reflect mutations in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which normally functions as a cyclic AMP-regulated Cl- channel. Aerosolized pharmacologic agents are being tested as novel treatment for these genetic ion transport defects. Amiloride aerosol inhibits excessive Na+ absorption, and pilot studies in adult patients with CF show improved biorheology and mucociliary clearance of airway secretions, as well as slowing of the decline in lung function. Phase III studies of amiloride in adults and adolescents are underway, and short-term safety studies in children are under way. Aerosolized uridine triphosphate (UTP) induces Cl- secretion in CF airway epithelia via non-CFTR Cl- channels. Initial safety studies suggest that acute aerosolized UTP is well tolerated, and acute studies of the effect on mucociliary clearance are underway. Pharmacotherapy that targets abnormal ion transport holds promise for the treatment of CF airway disease.

Adolescent↗

Prospective study of amikacin versus netilmicin in the treatment of severe infection in hospitalized patients.

PURPOSE: Four previous studies comparing netilmicin and amikacin have yielded inconclusive results concerning efficacy and rates of nephrotoxicity and ototoxicity. For this reason, we conducted a prospective, randomized, controlled trial of the two drugs in the treatment of hospitalized patients with severe infection. PATIENTS AND METHODS: A total of 202 patients were enrolled in the study; 100 received netilmicin and 102 received amikacin. Concomitant antimicrobials were restricted to metronidazole and benzylpenicillin. Peak and trough aminoglycoside levels were assayed within the first 36 hours and at least every 72 hours thereafter. A full blood cell count, serum electrolytes, creatinine, bilirubin, and liver enzymes were measured before therapy, weekly thereafter, and within 48 hours after the discontinuation of therapy. Nephrotoxicity and ototoxicity were assessed in patients. A standard agar dilution procedure was used to determine minimal inhibitory concentrations. RESULTS: No significant pretreatment differences were found between the two groups. Patients in the amikacin group responded significantly better to treatment than did patients in the netilmicin group (90% versus 79%; p less than 0.05). A notable finding was the markedly inferior response rate of Pseudomonas aeruginosa infections to netilmicin as compared with amikacin (13 of 24 with a favorable response compared with 25 of 26). No significant difference in ototoxicity was found, whereas nephrotoxicity appeared to be significantly less with amikacin (4% versus 12%, p less than 0.05). Although amikacin seemed less nephrotoxic than netilmicin, this may have been related to the significantly greater number of patients with initial renal dysfunction who received netilmicin. CONCLUSIONS: Amikacin appears to be significantly more efficacious than netilmicin for the treatment of P. aeruginosa infections, especially those in non-urinary tract sites. There is no apparent difference between the two drugs in terms of ototoxicity.

Acute Disease↗

A comparison of double beta-lactam combinations with netilmicin/ureidopenicillin regimens in the empirical therapy of febrile neutropenic patients.

In a randomized trial ceftazidime plus piperacillin or azlocillin, and netilmicin plus piperacillin or azlocillin were used as initial empirical therapy in 202 febrile neutropenic episodes. Netilmicin plus azlocillin was the most effective combination with a clinical response rate of 81% in clinically and microbiologically documented infections compared with 63% for ceftazidime plus piperacillin. All of the episodes of Gram-negative bacteraemia treated with azlocillin responded compared with 43% of those treated with piperacillin. Gram-positive organisms accounted for 52% of all bacteriologically documented infections and 40% of the febrile episodes were treated with vancomycin for presumptive or documented Gram-positive infection. Patients treated with netilmicin had significantly more nephrotoxicity than those given the double beta-lactam combinations (14.8% vs 3.5%; P less than 0.05). However, this difference was not shown in those patients who did not receive concurrent vancomycin or amphotericin. The double beta-lactam combinations were associated with more hypokalaemia (58.2% vs. 37.7%; P less than 0.05) and more colonization with yeasts (24% vs. 10.4%; P less than 0.05) but there was no evidence that their use was associated with prolongation of neutropenia. These results indicate that ceftazidime plus a ureidopenicillin would be adequate empirical therapy in situations where the concomitant use of nephrotoxic agents precludes the use of aminoglycoside containing combinations.

Adult↗

Do double-beta-lactam combinations prolong neutropenia in patients undergoing chemotherapy or bone marrow transplantation for hematological disease?

The total period of neutropenia was assessed in 174 episodes after chemotherapy or bone marrow transplantation in which patients received antibiotics for fever in a randomized prospective trial. Log rank analysis demonstrated no significant difference in the total duration of neutropenia between patients receiving netilmicin plus either piperacillin or azlocillin and those given ceftazidime plus either piperacillin or azlocillin. Of 86 patients in the single-beta-lactam group, 27 had a persistent neutrophil count of 0.1 x 10(9) per liter during treatment compared with 27 of 88 patients in the double-beta-lactam group, and 29 of 68 patients treated with the single-beta-lactam combination had a total period of neutropenia greater than 30 days versus 36 of 75 in the double-beta-lactam group. The use of two beta-lactam antibiotics rather than one does not appear to prolong neutropenia in patients undergoing treatment of hematological malignancy. However, in order to determine the effect of a single-beta-lactam combination, a similar carefully controlled prospective randomized study in which such treatment is compared with a non-beta-lactam-containing regimen is required.

Adult↗

Carriage of Candida species and C albicans biotypes in patients undergoing chemotherapy or bone marrow transplantation for haematological disease.

Six hundred and seventy four yeast isolates obtained from routine microbiological screening of 153 patients with haematological disease were identified and Candida albicans isolates biotyped over nine months to determine longitudinal and cross sectional patterns of yeast colonisation. A yeast microflora persisted in many patients despite the routine prophylactic use of oral antifungal agents. Analysis of the yeast species isolated on a cross sectional basis showed that C albicans accounted for 65% of yeasts isolated from the oral cavity but only 45% of the faecal yeast flora. Longitudinal changes in yeast flora occurred significantly more often in faecal samples than in oral samples and significantly less often in sites colonised with C albicans than in sites colonised with other species. No associations were found between the yeasts isolated and the nature of antifungal prophylaxis used, or the extent of a patient's stay in hospital.

Antifungal Agents↗

Antithrombin III in the diagnosis of infection in febrile neutropenic patients.

Antithrombin III levels in plasma were measured in 29 febrile neutropenic patients (31 episodes). They were lowest on day 2 in 62.5% of febrile patients and then increased or were normal in 81.3%. Low levels were present on day 2 in only 28.6% of patients with gram-negative infections, as compared with 33% of patients with doubtful infections.

Agranulocytosis↗

Apparent pulmonary mycetoma following invasive aspergillosis in neutropenic patients.

After the death from massive haemoptysis of two neutropenic patients who had developed apparent pulmonary mycetomas, two subsequent patients underwent successful resection of similar lesions. Histological examination of these lesions confirmed that these so called mycetomas were masses of devitalized lung tissue infiltrated with fungus. The term mycotic lung sequestrum is therefore proposed to distinguish this condition from a fungus ball arising in a previously formed cavity. A review of 34 similar cases reported previously showed that haemoptysis occurred in about half of the cases and was fatal in just over half of these. Medical treatment appears to have little impact on survival and early consideration of surgical intervention is important.

Adolescent↗