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Biomedical subjects

P Ball

Publications and source records attributed to P Ball.

At least 19 recordsLinked 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

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↗
PubMed1991

The future role and importance of macrolides.

The new macrolides, notably clarithromycin and azithromycin, are significant advances over previous agents. With an extended antibacterial spectrum, increased activity, improved absorption and excellent tissue and intracellular penetration, they realize therapeutic aims which have been increasingly sought in the 1980s. They are likely to find an extended role in respiratory tract infections, especially in community-acquired pneumonia, where the activity against beta-lactam-resistant bacteria and intracellular pathogens, e.g. Mycoplasma pneumoniae, Legionella spp. and Chlamydia pneumoniae have a significant role to play. Realistic twice or once daily dosing will prove a powerful argument for their use and the major improvement in gastrointestinal tolerance compared with erythromycin is likely to prove a deciding factor in their favour.

Anti-Bacterial Agents↗
PubMed1991

The role of temafloxacin in the community setting: an overview.

The use of new quinolones has become established therapy for many community infections including urinary tract infection, genital infection, soft tissue infection and some forms of lower respiratory tract infection. However, there has been an undercurrent of anxiety concerning their efficacy in pneumococcal infections. Temafloxacin has improved activity against pneumococci and its high oral bioavailability and excellent penetration into respiratory tissues now combine to provide a suitable profile for the management of a wider range of respiratory infections. Eradication rates in acute exacerbations of chronic bronchitis collated from individual studies are 98% overall and 100% in pneumococcal infections. Furthermore, eradication rates in smokers and the elderly illustrate significant advantages for temafloxacin when compared with previous quinolones. In pneumonia, a twice-daily temafloxacin regimen has given equivalent overall results to those of amoxycillin (84.6% vs 80%). In proven pneumococcal pneumonia, equivalent results (78.6% vs 78.4%) have been obtained with both drugs. A daily 600 mg dose of temafloxacin eradicated 94% of pneumococcal isolates in one study and in another this agent given twice-daily orally proved comparable to parenteral cephalosporin treatment. Temafloxacin shares with other quinolones excellent bacteriological and clinical efficacy against Haemophilus influenzae and Moraxella catarrhalis. These results and the lack of potential interaction with theophylline indicate temafloxacin to be suitable for domiciliary management of respiratory tract infections in addition to a broad range of other community infectious diseases.

Anti-Infective Agents↗
PubMed1990

Formation and metabolism of catecholestrogens in depressed patients.

The evidence that catecholestrogens are formed in the brain and exert behavioral effects in animal models suggest that these steroids might have psychotropic activities. In the present investigation, the formation and metabolism of catecholestrogens were studied in depressed patients. Twenty-four-hr urine samples were collected from 6 male patients (59 +/- 8 years) with endogenous retarded depression (subtype primary, endogenous, and recurrent according to Research Diagnostic Criteria) and from 12 male control subjects (51 +/- 4 years). The patients were treated with the monoamine oxidase inhibitor tranylcypromine (10-40 mg/day for 3-4 weeks). The concentrations of primary estrogens, 4- and 2-hydroxyestrogens and 2-methoxyestrogens, were measured in the urine samples after multiple chromatographic separation steps by radioimmunoassay. In the depressed patients, the excretion rates of 4-hydroxyestrogens were significantly lower than in control subjects. The ratio 2-methoxyestrogens:2-hydroxyestrogens as an index for 2-O-methylation was 3.8 +/- 1.6 in patients and 1.8 +/- 0.7 in controls. The increased methylation and reduced 4-hydroxylation rates of patients were not affected by treatment with tranylcypromine though the psychopathological state was improved by 46%. Therefore, it seemed unlikely that the observed alterations were pathognomonically relevant in these depressed patients. The alterations in the formation and methylation of catecholestrogens show that the depressed patients exhibited remarkable metabolic disturbances. The functional role of these disturbances remains to be clarified.

Depressive Disorder↗
PubMed1990

Formation, metabolism, and physiologic importance of catecholestrogens.

The metabolism of natural and synthetic estrogens is governed primarily by hydroxylations, leading to polyhydroxylated derivatives of the steroid molecule. In mammals aromatic hydroxylation is most prominent quantitatively. The 2- and 4-hydroxyestrogens (catecholestrogens) formed are secreted not only in high amounts in urine but are also present in significant quantities in different organs, such as the liver, pituitary gland, and hypothalamus. This A ring hydroxylation of primary estrogens is affected by peroxidases, tyrosinases, and unspecific monooxygenases by mechanisms still not completely understood. The activity of the aromatic hydroxylases is regulated not only with respect to the overall extent but also to the relative rate of hydroxylation at C-atoms 2 and 4. The metabolism of catecholestrogens may be divided into reversible and irreversible reactions, of which the reaction with the catechol-O-methyltransferase, and thereby the interaction with catecholamines, the conjugation, and the thioether formation are the most prominent. Low- and high-affinity binding is operative in binding to plasma proteins and receptors. Finally, irreversible binding to cellular macromolecules, such as proteins and deoxyribonucleic acid, and the oncogenic potential of natural and synthetic catecholestrogens are discussed.

Animals↗
PubMed1990

Emergent resistance to ciprofloxacin amongst Pseudomonas aeruginosa and Staphylococcus aureus: clinical significance and therapeutic approaches.

Sporadic emergence of resistance during therapy with ciprofloxacin has been noted since its use in clinical trials began. It has occurred particularly, although not exclusively, with Pseudomonas aeruginosa and Staphylococcus aureus, both of which have MICs in the range 0.5-2.0 mg/l. Although not invariably associated with clinical failure of therapy, emergence of resistance has usually occurred in infections either where large numbers of organisms are present or in tissues where ciprofloxacin concentrations may not be optimal, or where both factors apply. Care in selection of patients, attention to optimal duration of therapy and adequate dosage may help to prevent emergence of resistance but combination therapy has not proven effective. Resistance may in some bacterial strains be permanent but in others frequently reverts to normal sensitivity. In some situations, spread to other patients is a significant problem and treatment in isolation (or at home) may be advisable. Emergence of resistance to ciprofloxacin in these species usually occurs in recognizable situations and, in such circumstances, the availability of alternative therapy and the quantitative risk of the emergence of resistance must be balanced against potential benefit. Ciprofloxacin should never be used for trivial infections caused by staphylococci or P. aeruginosa.

Ciprofloxacin↗
PubMed1990

Overview of experience with ofloxacin in respiratory tract infection.

Ofloxacin is highly active against common respiratory pathogens including Haemophilus influenzae and Branhamella catarrhalis and has clinically applicable activity against Streptococcus pneumoniae, Staphylococcus aureus and Pseudomonas aeruginosa. Sputum, lung tissue and bronchial mucosal concentrations of ofloxacin equal or, in most cases significantly exceed the MICs of such pathogens. These in vitro attributes are reflected in the results of the worldwide ofloxacin clinical trial program which achieved overall response rates of 98% in lower respiratory tract infections, 83% in pneumonias and 87% to 95%, in open and comparative studies respectively, in patients with acute exacerbations of chronic bronchitis (CB). Overall bacterial eradication rates ranged from 70% for pneumococci and 84.5% for B. catarrhalis to 88.5% for H. influenzae. In lower respiratory infection ofloxacin gave equal or superior clinical results to amoxycillin or erythromycin therapy together with an overall bacterial eradication rate of 100%. Clinical results comparable with standard agents were also obtained in pneumonia, cure rates ranging from 77-89% at various dosages. Eradication rates proved greatest for H. influenzae (92%) and were satisfactory for Klebsiella spp. (80%), although less so for pneumococci (73%). Bacteriological eradication rates in acute exacerbations of chronic bronchitis ranged from 68% for pneumococcal infections, to 85% in B. catarrhalis and 94% in H. influenzae infections. Ofloxacin compared favourably with pivampicillin, co-trimoxazole and doxycycline clinically. A daily oral ofloxacin dose of 400 mg produced a good clinical response in 92% of patients or more. The available clinical data therefore substantially confirm the claim of ofloxacin to offer an effective alternative in many forms of acute bacterial respiratory infection, especially where H. influenzae and B. catarrhalis are involved.

Bronchitis↗