Biomedical subjects
Publications and source records attributed to P Ball.
Malassezia furfur has been shown to be capable of survival and reproduction in fat emulsions for parenteral nutrition, and this has been suggested as the source of serious systemic infections in neonatal intensive care units. Under conditions of use similar to those found in neonatal practice, the Pall TNA-1E filter was found to reliably retain this organism for up to 48 h.
A single-subject experimental design was used to obtain some preliminary findings on the plasma responses of catecholestrogens (CE) to acute exercise and brief, but exhaustive training on a cycle ergometer. One previously untrained eumenorrheic female (body fat: 26% VO2max: 43.3 ml x kg(-1) x min[-1]) participated in this study. Resting CE levels were for "total" (unconjugated + conjugated) 2-hydroxyestrogens (2-OHE) 162pg/ ml and 350 pg/ml in the follicular (FPh) and luteal phase (LPh), respectively. Plasma total 4-hydroxyestrogen (4-OHE) levels were 41 pg/ml in the FPh and 66 pg/ml in the LPh. For "total" 2-methoxyestrogens (2-MeOE), we found 257 pgl/ml in the FPh and 374 pg/ml in the LPh. Resting levels of 2-hydroxy CE following a period of brief, intensive training were decreased during the LPh (2-OHE: -38%; 2-MeOE: -19%), whereas 4-hydroxy CE were unaffected. After training, the formation of CE as expressed by the 2-OHE:E and 4-OHE:E ratios, was increased by 75% and 200% at rest, respectively. CE activity or O-methylation, as estimated from the 2-MeOE:2-OHE ratio, was higher following training (FPh: +22%; LPh: +30%). During acute exercise before training, we observed a small rise proportional to the exercise intensity in the plasma "total" primary estrogen concentrations (FPh: +28%; LPh: +16%), and no changes in either 2-OHE or 2 MeOE levels. Plasma concentrations of 4-OHE, however, doubled during maximal exercise intensity. The 2-OHE:E and 2-MeOE:2-OHE ratios did not alter during incremental exercise. Training effects on acute exercise responses were only noticed for 4-OHE, which contrary to pre-training conditions, now progressively decreased. The major findings of this study are that in response to training: a) during rest, a greater proportion of CE are formed from a lower amount of precursor hormone, b) the rate of O-methylation of CE increases.
Parenteral nutrition admixtures are complex pharmaceutical entities. The more closely they are examined, the more physico-chemical interactions emerge that could potentially affect stability. The move towards large scale hospital or commercial preparation, with a requirement for extended shelf life, and the increasing use of admixtures as vehicles for drugs and pharmaconutrients have created new formulation challenges for pharmaceutical scientists.
OBJECTIVE: In a preliminary report, the authors observed that clozapine was superior to haloperidol in the treatment of positive and negative symptoms in stable outpatients with schizophrenia. In this final report, they examine the effects of clozapine on positive and negative symptoms in patients with and without the deficit syndrome to determine which patients receive the positive symptom advantage of clozapine and the extent of clozapine's therapeutic effects on negative symptoms. In addition, they examine the long-term effects of clozapine on positive, negative, and affective symptoms, social and occupational functioning, and quality of life. METHOD: Seventy-five outpatients with schizophrenia, who met retrospective and prospective criteria for residual positive or negative symptoms, were entered into a 10-week double-blind, parallel-groups comparison of clozapine and haloperidol. Patients who completed the double-blind study were then entered into a 1-year open-label clozapine study. RESULTS: For patients who completed the 10-week double-blind study, clozapine was superior to haloperidol in treating positive symptoms. This effect was not observed in the intent-to-treat analyses. There was no evidence of any superior efficacy or long-term effect of clozapine on primary or secondary negative symptoms. Long-term clozapine treatment was associated with significant improvements in social and occupational functioning but not in overall quality of life. CONCLUSIONS: For schizophrenic patients who are able to tolerate clozapine therapy, clozapine has superior efficacy for positive symptoms but not negative symptoms and is associated with long-term improvements in social and occupational functioning for patients with and without the deficit syndrome.
The prevalence of chronic bronchitis is between 3% and 17% in most developed countries. However, higher rates in the range of 13 to 27% are encountered in less developed areas of the world. Acute exacerbations of chronic bronchitis (AECB) have usually been defined as the presence of increases in cough/sputum, sputum purulence, and dyspnea. However, recent investigations suggest that the severity of AECB may be divided into three stages based on the history of the patient: (1) previously healthy individuals; (2) patients with chronic cough and sputum and infrequent exacerbations; and (3) persons with frequent exacerbations or more severe chronic airflow limitation. Therapy for patients with less severe AECB include older and less expensive broad-spectrum antibiotics, while newer agents are indicated for patients with the most severe stage of AECB.
Fluoroquinolone antimicrobials have been available for over 10 years. Recent modifications to nuclear side-chains have enhanced both the antimicrobial and pharmacokinetic profiles of this class. Rapidly increasing antimicrobial resistance among community and hospital bacterial pathogens has diminished therapeutic options. Infections caused by such pathogens, including drug-resistant Streptococcus pneumoniae and multi-resistant Enterobacteriaceae are now treatable by few classes of antibacterials, one of these being the fluoroquinolones. Ciprofloxacin was one of the first effective agents available in both iv. and oral formulations for the treatment of Gram-negative infection, resistant to other antibiotics. More recent developments, such as sparfloxacin and grepafloxacin, are more effective in vitro against Gram-positive pathogens, although their safety profile may be less promising. Fluoroquinolones not yet in widespread clinical use, including trovafloxacin, clinafloxacin and moxifloxacin, hold considerable promise as community 'respiratory antimicrobials' and the results of clinical trials are awaited with anticipation. In this review, the three generations of fluoroquinolone development are examined and the relative antimicrobial, pharmacokinetic, clinical and safety profiles of available and developmental quinolones are compared.
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Exercise-induced menstrual problems are accompanied by an increase in catecholestrogen (CE) formation. It has been hypothesized that hypoestrogenemia may be secondary to an increased turnover from estrogens to CE, which then may disrupt luteinizing hormone release. In addition, the strong affinity of CE for the catecholamine-deactivating enzyme catechol-O-methyltransferase (COMT) has led to speculations about their possible role in safeguarding norepinephrine from premature decomposition during exercise. We investigated whether acute exercise on a cycle ergometer produces any changes in CE homeostasis. Nine untrained eumenorrheic women (body fat, 24.8 +/- 3.1%) volunteered for this study. Baseline plasma CE averages for total 2-hydroxyestrogens (2-OHE) were 218 +/- 29 (SE) pg/ml during the follicular phase (FPh) and 420 +/- 58 pg/ml during the luteal phase (LPh). 2-Methoxyestrogens (2-MeOE) measured 257 +/- 17 pg/ml in the FPh and 339 +/- 39 pg/ml in the LPh. During incremental exercise, total estrogens (E) increased, but 2-OHE and 2-MeOE levels did not significantly change in either phase. The 2-OHE/E ratio (measure of CE turnover) decreased during exercise in both menstrual phases, whereas the 2-MeOE/2-OHE ratio (correlates with COMT activity) did not significantly change. These findings suggest that there is insufficient evidence to conclude that brief incremental exercise in untrained eumenorrheic females acutely produces increased CE formation.
Catecholestrogens (CE) represent a major metabolic pathway in estrogen metabolism. Previous information on CE and training is limited to two cross-sectional studies that did not involve standardized training. Our purpose, by means of a prospective design, was to evaluate the effects of a brief, exhaustive training program on resting plasma concentrations of 2-hydroxy CE. The experimental design spanned two menstrual cycles; a control cycle and a training cycle. The subjects were nine previously untrained, eumenorrheic women [body fat: 24.8 +/- 1.0 (SE) %]. Data were collected during the follicular (FPh) and the luteal phases (LPh). Posttraining FPh and LPh tests were held the day after the last day of a 5-day period of training on a cycle ergometer. Total 2-hydroxyestrogens (2-OHE) averaged 200 +/- 29 pg/ml during the FPh and 420 +/- 54 pg/ml during the LPh (P < 0.05). Levels of total 2-methoxyestrogens (2-MeOE) were 237 +/- 32 pg/ml during the FPh and 339 +/- 26 pg/ml during the LPh (P < 0.05). After training, although the plasma levels of 2-OHE significantly decreased (21%; P < 0.05) during the LPh, the actual CE formation (as estimated from the 2-OHE-to-total estrogens ratio) increased (+ 29%; P < 0.05). CE activity, as expressed by the 2-MeOE-to-2-OHE ratio, showed significantly higher values in both phases (FPh, + 14%; LPh, + 13%; P < 0.05). At the same time, resting levels of norepinephrine (NE) were increased by 42% (P < 0.05). CE strongly inhibit biological decomposition of NE by catechol-O-methyltransferase (COMT). Results of the present study suggest that, in response to training, CE are increasingly competing with the enzyme COMT, thus preventing premature NE deactivation.
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It has been hypothesized that exercise-related hypo-estrogenemia occurs as a consequence of increased competition of catecholestrogens (CE) for catechol-O-methyltransferase (COMT). This may result in higher norepinephrine (NE) concentrations, which could interfere with normal gonadotropin pulsatility. The present study investigates the effects of training on CE responses to acute exercise stress. Nine untrained eumenorrheic women (mean percentage of body fat +/-SD: 24.8 +/- 3.1%) volunteered for an intensive 5-day training program. Resting, submaximal, and maximal (tmax) exercise plasma CE, estrogen, and catecholamine responses were determined pre- and post training in both the follicular (FPh) and luteal phase (LPh). Acute exercise stress increased total primary estrogens (E) but had little effect on total 2-hydroxyestrogens (2-OHE) and 2-hydroxyestrogen-monomethylethers (2-MeOE) (= O-methylated CE after competition for catechol-O-methyltransferase). This pattern was not significantly changed by training. However, posttraining LPh mean (+/-SE) plasma E, 2-OHE, and 2-MeOE concentrations were significantly lower (P < 0.05) at each exercise intensity (for 2-OHE: 332 +/- 47 vs. 422 +/- 57 pg/mL at tmax; for 2-MeOE: 317 +/- 26 vs. 354 +/- 34 pg/mL at tmax). Training produced opposite effects on 2-OHE:E ratios (an estimation of CE formation) during acute exercise in the FPh (reduction) and LPh (increase). The 2-MeOE:2-OHE ratio (an estimation of CE activity) showed significantly higher values at tmax in both menstrual phases after training (FPh: +11%; LPh: +23%; P < 0.05). After training, NE values were significantly higher (P < 0.05). The major findings of this study were that: training lowers absolute concentrations of plasma estrogens and CE; the acute exercise challenge altered plasma estrogens but had little effect on CE; estimation of the formation and activity of CE suggests that formation and O-methylation of CE proportionately increases. These findings may be of importance for NE-mediated effects on gonadotropin release.
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Following earlier work identifying the difficulties of defining the subtalar neutral position, the authors have developed new techniques to measure the ranges of inversion and eversion in normal subjects. A test rig has been designed and constructed to apply a known torque about an anterior posterior axis and an electrogoniometer has been used to measure the resulting movements. The neutral position was defined as that position corresponding to the footplate being horizontal and the leg vertical. In a study of 100 normal subjects (50 female/50 male), it has been shown that the average overall range of motion decreased from 53.2 degrees in 20-year-olds to 44.3 degrees in 60-year-olds. It was also demonstrated that females had a greater range of motion than males, but that this difference reduced with age. This fact was largely accounted for by a decrease in the range of eversion in female subjects. RELEVANCE:--Hindfoot motion is essential for human walking, but accurate measurement is difficult because of the structure of the joints involved. This paper describes the development of a technique using electrogoniometry, for carrying out measurement of passive inversion and eversion of the hindfoot in a sample of healthy adults. It further highlights the difficulties in carrying out an accurate evaluation of hindfoot motion on which to base clinical decisions.
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Bacterial infection is an important cause of exacerbations of chronic bronchitis, which can precipitate both direct toxic and host-mediated inflammatory bronchial epithelial damage. Repeated episodes, especially when caused by Haemophilus influenzae (the major pathogen) may be associated with more rapid deterioration in respiratory function. Criteria to identify patients with more severe disease and those who require either hospitalization or intensive care have been developed and can improve mortality. Antibiotic therapy has an accepted place in management, and predictors of the outcome of exacerbations have now been developed that allow severity staging of individual episodes. Nevertheless, despite the recognition of excessive failure rates due to increasing bacterial resistance and poor respiratory kinetics, many patients continue to receive empiric therapy with amoxicillin and other oral beta-lactams. Less empiric management guidelines, produced in Europe and North America and based on such criteria, now provide a framework for rational prescribing. Perhaps more importantly, it is now possible to design and perform placebo- and comparator-controlled studies of new antibacterials, such as the fluoroquinolones and azalides, with improved potency and kinetic properties. This will enable both an assessment of their place in the management of exacerbations in at-risk patients with severe disease and an evaluation of their longer-term role in the prevention of a decline in respiratory function consequent upon repeated and ineffectively treated exacerbations.
OBJECTIVE: The authors examined the efficacy of fluoxetine augmentation of clozapine treatment response in schizophrenic outpatients who, despite adequate treatment with clozapine, continued to exhibit persistent positive or negative symptoms. METHOD: Thirty-three patients completed on 8-week, double-blind, parallel-groups comparison of adjunctive fluoxetine and placebo. RESULTS: There were no significant differences in positive, negative, depressive, or obsessive-compulsive symptoms between patients given adjunctive fluoxetine or placebo. CONCLUSIONS: These results suggest that fluoxetine is not effective in augmenting clozapine treatment response.
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