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Biomedical subjects

P Ball

Publications and source records attributed to P Ball.

At least 19 recordsLinked to original sources
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↗
PubMed1989

Adverse reactions and interactions of fluoroquinolones.

Recent research into fluoroquinolone antibacterials has led to the discovery of a number of compounds with greatly improved potency, spectrum, pharmacokinetics and clinical efficacy. In general their safety and tolerance mirrors these attributes. Like previous naphthyridines, cinnolines, and fluoroquinolones, these agents may cause gastrointestinal, central nervous system, and cutaneous reactions, but these are usually mild and self-limiting, affect 5-10% of patients only and rarely require withdrawal from therapy. Extremely rarely, more serious CNS effects including fits and psychosis may accompany high dose therapy. Potentially serious problems, predicted by animal testing and including erosive arthropathy in juvenile rats and dogs, cataract formation and renal damage secondary to crystalluria, have not been encountered in clinical use. All of the new agents give positive results in some tests for mutagenesis but there is no evidence for mutagenicity or carcinogenicity in man. However, the possibility of mutagenesis and joint damage restricts the use of fluoroquinolones in children to life-saving indications only. Interactions may occur with other drugs. Absorption of these agents is interfered with by co-administered antacids, although not by H2 antagonists. Oxo-metabolites of enoxacin and, to a lesser extent, pefloxacin and ciprofloxacin interfere with the hepatic elimination of theophylline and caffeine and may result in toxicity due to these agents if dosage is not modified. With the exception of these avoidable events, the fluoroquinolones have proved a particularly safe group of agents in clinical use.

4-Quinolones↗
PubMed1988

Modulation of gonadotropin-releasing hormone receptor concentration in cultured female rat pituitary cells by estradiol treatment.

Short-term (0.5-4 h) treatment of rat pituitary cells in culture with estradiol (E2) results in a significant decrease of Gonadotropin-Releasing Hormone (GnRH) induced LH-release. We studied whether changes in the concentrations of GnRH-receptors (GnRH-R) might account for this phenomenon: pituitary cells from adult female rats were incubated for 4 or 24 h in the presence or absence of 10(-9) M E2. Then saturation curves of D-Ala6-des-Gly10-GnRH ethylamide binding were obtained. In addition, binding studies were carried out in cultures incubated for 0.5, 1, 2 or 4 h with or without 10(-9) M E2 using a near saturating concentration of GnRH-analog. No changes of GnRH-R affinity occurred (4 h experiments: Ka in vehicle treated cells: 0.94 +/- 0.2 x 10(9) M-1, Ka in E2 treated cells: 1.06 +/- 0.3 x 10(9) M-1; 24 h experiments: Ka vehicle: 0.95 +/- 0.2 x 10(9) M-1, Ka E2: 0.82 +/- 0.3 x 10(9) M-1). The GnRH-R concentrations, however, were significantly reduced (44 +/- 3%; P less than 0.001) by 4 h E2 treatment and increased (by 68 +/- 8%; P less than 0.01) by 24 h of E2 treatment. The GnRH induced LH-release in aliquots of the same cell preparations was significantly reduced after 4 h and markedly increased after 24 h of E2 treatment. The experiments on the time-course of the reduction of D-Ala6-GnRH-binding by E2 treatment showed that the number of GnRH-R was significantly decreased (24 +/- 1%; P less than 0.05) already after 0.5 h of exposure to the estrogen. This is also the time period after which the negative E2-effect on GnRH-induced LH-release becomes significant. These data provide first evidence that the short-term negative E2-effect on GnRH induced LH-release by rat pituitary cells in culture could be mediated via a reduction of available GnRH-R.

Animals↗