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Biomedical subjects

P Ball

Publications and source records attributed to P Ball.

At least 73 records · Page 4Linked to original sources
PubMed1995

Chemotherapy for chronic bronchitis. Controversies.

Chronic bronchitis is a common inflammatory disease of the airways characterised by cough, sputum production and associated features such as dyspnoea and respiratory obstruction. It has a poor prognosis once fully developed and imposes a heavy financial burden on affected societies. Chronic bronchitis is subject to periodic exacerbations in which the role of bacterial infection and the rightful place of antibiotic therapy is only slowly emerging, largely due to the non-homogeneity of the populations under study. Haemophilus influenzae is implicated as the pathogen in more than half of all bacterial exacerbations, Streptococcus pneumoniae and Moraxella catarrhalis accounting for a further third. Viruses and mycoplasmas are also involved. Some 18-25% of patients receiving domiciliary therapy may fail to respond to initial treatment, calling into question the efficacy of antibiotics in acute exacerbations. In part this may relate to sub-optimal respiratory pharmacokinetics as most antibiotics are quite effective against sensitive respiratory pathogens in vitro. However, bacterial resistance rates against traditional agents are rising rapidly in Europe and new agents are needed to counter this threat. Paradoxically few such agents have been shown to improve on the results of amoxycillin and other standard drugs, probably because most trials include patients with exacerbations of only mild-to-moderate severity due to sensitive pathogens. Since recent large scale studies have demonstrated the efficacy of antibiotic therapy compared with placebo in defined exacerbations, use of these definitions has allowed more realistic assessment of new agents which, in terms of improved antibacterial potency and respiratory pharmacokinetics, should offer superior efficacy. Regression analysis of a large scale general practice survey in the UK has now shown the frequency of exacerbations and the presence of co-morbid conditions to correlate significantly with a poor therapeutic outcome and thus, by implication, with severity. Future trials of antibacterial chemotherapy for acute bacterial exacerbations of chronic bronchitis should incorporate such criteria so that real differences between existing and improved compounds can be assessed.

Anti-Bacterial Agents↗
PubMed1995

Tolerability of fluoroquinolone antibiotics. Past, present and future.

New fluoroquinolones have been in clinical use for 10 years and have an excellent record of safety and tolerance. The main elements of their adverse reaction profile were predictable from human experience with precursor naphthyridines and quinolones, and from toxicological studies in animals. Thus gastrointestinal reactions (1 to 5%), skin disturbances (less than 2.5%) and central nervous system (CNS) effects (usually around 1 to 2%) were anticipated. Individual group members exhibit particular properties in relation to their chemical structures, for example the phototoxicity associated with 8-halogenation of the nucleus and found to be a particular problem with lomefloxacin and sparfloxacin. Other members, for example ofloxacin, are linked to a higher than usual incidence of CNS reactions and psychological disturbance. However, despite increasing usage, none of the present group have been implicated in joint damage in children, which had been a major concern following reports of this effect in juvenile animals in chronic toxicity studies. Furthermore, intravenous formulations appear to have no associated increase in toxicity. Crystalluria with associated renal damage, originally thought likely to limit intravenous dosage, has not proved to be a problem in humans. Clinically significant interactions may occur but, as with those involving various NSAIDs and potentially leading to convulsions, they have been defined and are thus avoidable. Postmarketing surveillance studies and prescription event monitoring have largely confirmed the limited adverse reaction profile defined during clinical trials. However, some unexpected reactions have appeared after launch, most notably the episodes of haemolysis, renal failure and hypoglycaemia which led to the withdrawal of temafloxacin. These effects have not been observed with other fluoroquinolones. However, severe tendinitis appears to be a group effect, albeit rare, and anaphylactoid reactions have been reported with several of the fluoroquinolone group, often in AIDS patients. The new fluoroquinolones are essentially a well tolerated group of antibacterials, the benefits of which clearly outweigh their disadvantages in a wide range of indications. Clinical efficacy has been a larger determinant of which members have succeeded in the marketplace than potential toxicity. However, the lesser potential for adverse effects of some of the class, e.g. norfloxacin, ofloxacin and ciprofloxacin, has undoubtedly led to their more widespread use. For others, e.g. enoxacin, limited clinical utility and a perception of increased toxicity have resulted in sidelining. There remains the potential for development of safer and yet more active fluoroquinolones via chemical manipulation both of the nucleus and the side chain substituents.

Anti-Infective Agents↗
PubMed1995

Acute infective exacerbations of chronic bronchitis.

Patients with an acute infective exacerbation of chronic bronchitis (AECB) (n = 471) were enrolled into a computer-based general-practice study to determine whether features of past history, presenting symptoms, or findings on examination were predictive of failure to recover. The median age was 68, 56.3% were male, and 82% were current or ex-smokers. All had daily sputum production and 57.5% had moderate or severe airflow obstruction. During the AECB 11.5% were pyrexial, and 80.7% had abnormal auscultatory findings; about half had moderate to severe increases in dyspnoea and airflow obstruction, and the majority had increases in sputum volume and/or purulence. The median number of AECBs in the previous year was three, and one-third of patients had cardiopulmonary disease. The only factors significantly (p < 0.05) predicting failure to recover from an AECB were historical. Neither clinical features at presentation nor antibiotic treatment affected recovery. Coexistent cardiopulmonary disease was a risk factor for returning with a chest problem and for being referred to hospital. The number of chest infections in the previous 12 months was a risk factor for returning with a chest problem. The higher the number of chest infections, the higher the odds of returning with a chest problem. The best combination predicting return with a chest problem was history of cardiopulmonary disease and more than four previous AECBs in the last 12 months. The sensitivity was 75% and specificity 47%.

Acute Disease↗
PubMed1994

Bacterial resistance to fluoroquinolones: lessons to be learned.

Resistance to fluoroquinolone antibacterials has emerged in a limited form, largely amongst certain specific species and often restricted to single clones of these pathogens. Mediated by chromosomal mutation, the major mechanisms are alterations in gyrase subunits and reduced penetration associated with decreased outer membrane protein production. Resistance is most commonly seen to emerge amongst pathogens with higher than average initial MICs, particularly affected species being Pseudomonas aeruginosa and the staphylococci. Resistance is more likely to be encountered when such pathogens are exposed to concentrations at or below the MIC, which may result either from underdosage, the presence of the organism in a sequestered site, e.g. bone or prostate, or from confounding factors such as the presence of pus, indwelling prostheses or interactions which reduce absorption from the gastrointestinal tract. Repetitive use of these agents and continued use of fluoroquinolone precursors, such as nalidixic acid, may also contribute to resistance emergence. Most resistance is appearing amongst hospitalised patients and much of the apparent burden reflects horizontal cross-infection of many patients by a single resistant clone. There is very limited data linking increasing community use of fluoroquinolones with resistance emergence amongst pathogens such as Escherichia coli. In the main, the emergence of resistance can be anticipated and perhaps prevented or avoided for the sorts of risk groups and pathogens described. The use of adequate dosage by appropriate routes of administration in suitable patients and implementation of surveillance procedures for those at risk will minimise such problems. Policies for the effective use of these valuable agents should be part of everyday practice in hospitals.

Anti-Infective Agents↗
PubMed1994

Efficacy and safety of cefprozil versus other beta-lactam antibiotics in the treatment of lower respiratory tract infections.

Cefprozil was evaluated in four multicentre comparative studies in the treatment of acute respiratory tract infections. In two studies, cefprozil 500 mg q. 12 hours was compared to cefaclor 500 mg q. eight hours for ten days of therapy. Randomization was on a 2:1 (cefprozil:cefaclor) basis in the European centres and 1:1 in North America. The clinical efficacy in acute bronchitis was 88% (284 out of 324 patients) for cefprozil and 88% (183 out of 208) for cefaclor, with successful bacteriological eradication of the causative pathogen in 86% and 82% of the patients, respectively. Amongst the patients with acute exacerbations of chronic bronchitis, the clinical response rate of 80% (59 out of 74) for cefprozil appeared superior to that of cefaclor at 62% (p = 0.067), whilst the bacteriological response rates were 62% (36 out of 58) for cefprozil and 74% (20 out of 27) for cefaclor. In pneumonia, the clinical response rates for cefprozil and cefaclor therapy were similar, 82% vs. 79%, although bacteriological eradication rates were better for cefprozil at 82% than for cefaclor at 71%. In the comparison of cefprozil with cefuroxime axetil, a total of 170 patients were evaluable. The clinical and bacteriological response rates for cefprozil of 95% and 100% were better than those for cefuroxime axetil 500 mg q. 12 hours of 84% and 75%, respectively. In the cefprozil vs. amoxicillin-clavulanate, 500 mg q. eight hours comparative study, the two antibiotics displayed no significant difference in clinical or bacteriological responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Effects of atrial natriuretic factor on anterior pituitary hormone secretion in normal man.

The effects of intravenous human atrial natriuretic factor ANF(99-126) administration on anterior pituitary hormone secretion have not been extensively investigated in humans. We repeatedly studied 10 healthy volunteers (5 female, 5 male, aged 28 +/- 2 years) on 2 occasions, 3 days apart. In randomized, single blind order, subjects received pretreatment with either placebo or intravenous ANF(99-126) (bolus 100 micrograms/kg, 30-min infusion of 0.1 micrograms/kg.min). Subsequently on both occasions subjects received a combined intravenous bolus injection of pituitary releasing hormones (200 micrograms thyrotropin releasing hormone, 100 micrograms gonadotropin releasing hormone and 100 micrograms human adrenocorticotropin releasing hormone; Bissendorf, Hannover, FRG). Plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), thyrotropin (TSH), prolactin, ANF and cyclic guanosine monophosphate (GMP) were determined by radioimmunoassay. ANF(99-126) treatment induced a significant reduction in basal ACTH plasma concentrations and tended to decrease basal plasma cortisol. The TSH response to combined releasing hormone administration was significantly diminished after ANF(99-126) pretreatment. In women, the releasing hormone induced prolactin increase was reduced after ANF(99-126) pretreatment. With the present study design, ANF(99-126) did not alter the basal or releasing hormone stimulated plasma concentrations of cortisol, LH, FSH and GH. Releasing hormone administration did not affect ANF and cyclic GMP plasma levels. In humans, effects of natriuretic peptides on anterior pituitary hormone secretion may have to be considered with investigational or therapeutic administration of ANF analogues or agents interfering with the ANF metabolism.

Adult↗