PubMed Health⌕ Search

Biomedical subjects

A Allen

Publications and source records attributed to A Allen.

At least 55 records · Page 3Linked to original sources
PubMed2000

The effect of food on the bioavailability of oral gemifloxacin in healthy volunteers.

The effect of food on the bioavailability of gemifloxacin was investigated at two doses (320 and 640 mg) in healthy male and female volunteers. A total of 21 subjects entered the open label, four-period crossover study. Each subject received single oral doses of 320 and 640 mg in the fasted state and after a high fat meal, on separate dosing occasions in a randomised fashion. There was on average, a 3% (95% CI (0.88, 1.07)) and 12% (95% CI (0.79, 0.97)) reduction in AUC and a 12% (95% CI (0.76, 1.02) and 14% (0.75, 1.00) reduction in Cmax after the 320- and 640-mg doses, respectively. The results indicate a minor effect of food on bioavailability of gemifloxacin (320 and 640 mg). Such a reduction in systemic exposure would be considered to be not clinically relevant. Tmax data were inconclusive but indicated a possible slight delay in Tmax of, on average, 0.75 and 0.21 h after the 320- and 640-mg doses, respectively. Delays of this magnitude in reaching maximum concentrations are unlikely to be of clinical importance for an antibiotic drug. Both 320 and 640 mg gemifloxacin were well tolerated in fed and fasted states by healthy volunteers. It can be concluded therefore, that gemifloxacin can be taken with and without food.

Adult↗
PubMed2000

The effect of ferrous sulphate and sucralfate on the bioavailability of oral gemifloxacin in healthy volunteers.

Sucralfate is a cytoprotectant with antacid properties and ferrous sulphate is commonly prescribed for iron-deficiency anaemia. This open, randomized, single-dose, five-way crossover study investigated the effect of sucralfate and ferrous sulphate on the bioavailability of gemifloxacin, a novel fluoroquinolone antimicrobial. Twenty-seven healthy male volunteers received gemifloxacin, 320 mg p.o., alone, 3 h after sucralfate (2 g) or ferrous sulphate (325 mg), or 2 h before sucralfate or ferrous sulphate. Each subject received all five dosing regimens in random order with at least 6 days between regimens. Plasma samples collected up to 48 h after dosing with gemifloxacin, were assayed for gemifloxacin to determine pharmacokinetic parameters. Administration of gemifloxacin 3 h after sucralfate produced a marked decrease of 53% in the area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-infinity), and a decrease of 69% in the maximal plasma concentration (Cmax). Administration of gemifloxacin 3 h after ferrous sulphate resulted in only a modest reduction of 11% in AUC0-infinity and of 20% in Cmax, which was not considered to be clinically significant. In contrast, at the doses used neither sucralfate nor ferrous sulphate altered gemifloxacin bioavailability when it was administered 2 h before either of these agents. Gemifloxacin was well tolerated in all the regimens. The results of this study support the dosing recommendation that gemifloxacin can be safely administered at least 2 h before sucralfate or ferrous sulphate, or at least 3 h after ferrous sulphate.

Adolescent↗
PubMed2000

Interaction of Bordetella pertussis with human respiratory mucosa in vitro.

The human respiratory tract pathogen Bordetella pertussis is the major cause of whooping cough in infants and young children, and also causes chronic cough in adults. B. pertussis infection damages ciliated epithelium in the respiratory tract. However, the interaction of the bacterium with the respiratory mucosa is poorly understood, and previous studies have either utilized animal tissue which may not be appropriate, or isolated cell systems which lack the complexity of the respiratory mucosa. We have studied the interaction of B. pertussis strain BP536 with human nasal turbinate tissue in an air-interface organ culture over 5 days. We have also compared infection by BP536 with two other strains, Tohama I and CN2992, to determine whether the interactions observed with BP536 are consistent, and, in both nasal turbinate and adenoid organ cultures at 24 h, to determine whether there were differences between tissue from different parts of the respiratory tract. BP536 adhered to cilia, most commonly at their base, and disorganized their spatial arrangement, they also adhered to damaged tissue and mucus, but very rarely to unciliated cells. Within the first 24 h there was a five-fold increase in bacterial density on ciliated cells, and the total number of adherent bacteria increased up to 96 h. Infection caused increased mucus at 24h and an increase in damaged epithelium from 72 h which involved both ciliated and unciliated cells. The number of residual ciliated cells did not decrease after 72 h. The three different strains of B. pertussis exhibited similar interactions with the mucosa, and there was no tissue specificity for adenoid or turbinate tissue. We conclude that B. pertussis adhered to multiple sites on the mucosa and caused hypersecretion and epithelial damage which are the pathological changes described in vivo.

Adenoids↗
PubMed2000

Smaller organ tissue mass in the elderly fails to explain lower resting metabolic rate.

We previously reported our in vivo prediction of whole body resting energy expenditure (REE) using magnetic resonance imaging and echocardiography-derived organ volumes combined with published organ tissue metabolic rates. The models, developed in young healthy persons from predicted and measured variables, were highly correlated (e.g., calculated vs. measured REE, r = 0.92, p < 0.001), with no significant differences (p = NS) between them. This study employed the same approach to determine whether possible age-related decreases in organ tissue mass may account for the lower REE commonly reported in elderly persons. Measurements of REE (REEm) were acquired by indirect calorimetry. Calculated REE (REEc) models were developed from measured tissues and organs, and energy flux rates were assigned for each of the seven tissue/organ components, as reported by Elia. Older men (n = 6) and women (n = 7) had significantly lower REEm compared to REEc (p = 0.001). The magnitude of the differences were 13% and 9.5%, respectively, for men and women. These preliminary data suggest that factors other than organ atrophy may contribute to the lower metabolic rate of older persons. Further studies are required to investigate whether there is a reduction in the oxidative capacity of individual organs and tissues.

Absorptiometry, Photon↗
PubMed2000

Pharmacokinetics and tolerability of gemifloxacin (SB-265805) after administration of single oral doses to healthy volunteers.

Gemifloxacin (known as SB-265805 or LB-20304) is a potent, novel fluoroquinolone compound with a broad spectrum of antibacterial activity. The pharmacokinetics and tolerability of oral gemifloxacin were characterized in healthy male volunteers after a single dose of 20, 40, 80, 160, 320, 600, or 800 mg. Multiple serum and urine samples were collected and analyzed for gemifloxacin using high-performance liquid chromatography with fluorescence detection. Safety assessments included vital signs, 12-lead electrocardiogram readings, hematology, clinical chemistry, urinalysis, and adverse-experience monitoring. Gemifloxacin was rapidly absorbed after all doses. Maximum concentrations of gemifloxacin in serum (C(max)) were achieved approximately 1 h after dosing, after which concentrations in serum declined in a biexponential manner. Values of C(max) and the area under the concentration-time curve in serum from 0 h to infinity (serum AUC(0-infinity)) increased linearly with dose. Serum AUC(0-infinity) values (mean +/- standard deviation) were 0.65+/-0.01, 1.28+/-0.22, 2.54+/-0.31, 5.48+/-1.24, 9.82+/-2.70, 24.4+/-7.1, and 31.4+/-7.6 microg. h/ml following 20-, 40-, 80-, 160-, 320-, 600-, and 800-mg doses, respectively. The terminal phase elimination half-life was independent of dose, with an overall mean of 7.4+/-2.0 h. The profiles indicated that the pharmacokinetic profile is suitable for a once-daily dosing regimen. Approximately 25 to 40% of the administered dose was excreted unchanged in the urine, and renal clearance (ca. 150 ml/min) was independent of dose. There were no significant changes in clinical chemistry, hematology, or urinalysis parameters, vital signs, or 12-lead electrocardiogram readings in subjects, irrespective of dose. The results of these studies support the further investigation of once-daily administration of gemifloxacin.

Administration, Oral↗
PubMed2000

The human trefoil peptide, TFF1, is present in different molecular forms that are intimately associated with mucus in normal stomach.

BACKGROUND: TFF1 is a 6.5 kDa secreted protein that is expressed predominantly in normal gastric mucosa. It is coexpressed with mucins and it can form dimers via a free carboxy terminal cysteine residue. AIMS: To investigate the molecular forms of TFF1 that are present in normal human stomach and the association of the different molecular forms with mucus. SUBJECTS: All subjects had macroscopically normal stomachs at gastroscopy. None had a significant past medical history. METHODS: TFF1 was detected in normal gastric mucosa and adherent mucus by western transfer analysis after electrophoresis on reducing and non-reducing polyacrylamide gels. In some instances, proteins were fractionated by caesium chloride density gradient centrifugation prior to detection of TFF1. The location of TFF1 in gastric mucosa with an intact adherent mucus layer was assessed by immunohistochemistry. RESULTS: Three different molecular forms of TFF1 were detected: TFF1 monomer, TFF1 dimer, and a TFF1 complex with an apparent molecular mass of about 25 kDa. TFF1 was present at higher concentrations than realised previously. The TFF1 complex was present in the adherent mucus gel layer but while its interaction with mucin was destabilised by caesium chloride, the interaction between mucin and the TFF1 dimer was resistant to caesium chloride. CONCLUSIONS: Most of TFF1 in normal human gastric mucosa is present in a complex that is stabilised by a disulphide bond. TFF1 is intimately associated with mucus. The high concentration, colocalisation, and binding of TFF1 to gastric mucus strongly implicate TFF1 in gastric mucus function.

Blotting, Western↗
PubMed2000

School preparation for the asthmatic student.

Questionnaires given to school nurses were used to collect data regarding emergency asthma equipment and plans. Sixty-three percent reported <10 asthmatic visits per month, 25% reported 10-50, and 12% reported >50. Only 20% of school nurses reported that 75%-100% of asthmatic students had an emergency plan, and 24% did not know if asthmatic students had a plan. Only half of the nurses had input into the plan. Equipment varied: 16% had oxygen, 45% had peak flow meters, 0% had MDIs, and 20% had nebulizers available. Many asthmatic students lack emergency plans, and many school nurses are not involved in the plans.

Asthma↗
PubMed2000

Rosiglitazone does not alter the pharmacokinetics of metformin.

Rosiglitazone is a potent oral antidiabetic agent of the thiazolidinedione class that works through activation of the peroxisome proliferator-activated nuclear receptor. It improves insulin sensitivity in peripheral tissues and effectively lowers blood glucose in patients with type 2 diabetes. Metformin is a dimethyl-biguanide, also used in type 2 diabetes, that lowers fasting blood glucose primarily by decreasing hepatic glucose output. Rosiglitazone and metformin reduce plasma glucose concentrations via different mechanisms and thus could potentially be used in combination to optimize glycemic control. This study evaluated the effects of the coadministration of these two agents on the pharmacokinetics of both rosiglitazone and metformin. Sixteen male volunteers (22-55 years old) received oral metformin (500 mg every 12 hours), rosiglitazone (2 mg every 12 hours), or the combination each for 4 days. Plasma collected on day 4 of each regimen was assayed for rosiglitazone and metformin concentrations. Oral doses of rosiglitazone and metformin were safe and well tolerated when administered alone or in combination. There were no clinically significant episodes of hypoglycemia or increased blood lactic acid levels following treatment with any regimen. Coadministration of rosiglitazone and metformin had no significant effects on the steady-state pharmacokinetics (AUC(0-12 h), Cmax, tmax, or t1/2) of either drug. The authors conclude that rosiglitazone can be safely administered with metformin and, due to the different mechanisms of action of these agents, may offer a therapeutic advantage in patients with type 2 diabetes mellitus.

Acidosis, Lactic↗
PubMed2000

Organisation of services for acute stroke in Scotland--report of the Scottish stroke services audit.

An audit was undertaken of hospital service provision for acute strokes in Scotland, using as a template key recommendations in the four SIGN guidelines on management of stroke. A questionnaire and structured interview was undertaken of key personnel in the 43 Trusts and three directly managed units providing in-patient stroke care in Scotland, and the 15 Health Boards commissioning stroke care. All Trusts and Health Boards participated and a complete set of information for each was recorded on a data-base and analysed. This report gives an overview for 14 key components of an integrated stroke service with results presented in four bands according to Trust type determined by the number of strokes admitted. No Trust provided all key components and for a few components a lack of provision was widespread, e.g. fast-track assessment clinics for TIA and minor stroke, access to CT scanning within 48 hours. Variation occurred between Trusts of similar size, between Trusts of different sizes. Overall the Health Boards were at a preliminary stage in the development of stroke specific service specifications. The results of the audit are a view of stroke services around April 1998, and should enable commissioners and providers to consider how to progress implementation of the clinical guidelines on stroke care.

Acute Disease↗
PubMed1999

Randomized secondary prevention trial of azithromycin in patients with coronary artery disease and serological evidence for Chlamydia pneumoniae infection: The Azithromycin in Coronary Artery Disease: Elimination of Myocardial Infection with Chlamydia (ACADEMIC) study.

BACKGROUND: Chlamydia pneumoniae commonly causes respiratory infection, is vasotropic, causes atherosclerosis in animal models, and has been found in human atheromas. Whether it plays a causal role in clinical coronary artery disease (CAD) and is amenable to antibiotic therapy is uncertain. METHODS AND RESULTS: CAD patients (n=302) who had a seropositive reaction to C pneumoniae (IgG titers >/=1:16) were randomized to receive placebo or azithromycin, 500 mg/d for 3 days, then 500 mg/wk for 3 months. Circulating markers of inflammation (C-reactive protein [CRP], interleukin [IL]-1, IL-6, and tumor necrosis factor [TNF]-alpha), C pneumoniae antibody titers, and cardiovascular events were assessed at 3 and 6 months. Treatment groups were balanced, with age averaging 64 (SD=10) years; 89% of the patients were male. Azithromycin reduced a global rank sum score of the 4 inflammatory markers at 6 (but not 3) months (P=0. 011) as well as the mean global rank sum change score: 531 (SD=201) for active drug and 587 (SD=190) for placebo (P=0.027). Specifically, change-score ranks were significantly lower for CRP (P=0.011) and IL-6 (P=0.043). Antibody titers were unchanged, and number of clinical cardiovascular events at 6 months did not differ by therapy (9 for active drug, 7 for placebo). Azithromycin decreased infections requiring antibiotics (1 versus 12 at 3 months, P=0.002) but caused more mild, primarily gastrointestinal, adverse effects (36 versus 17, P=0.003). CONCLUSIONS: In CAD patients positive for C pneumoniae antibodies, global tests of 4 markers of inflammation improved at 6 months with azithromycin. However, unlike another smaller study, no differences in antibody titers and clinical events were observed. Longer-term and larger studies of antichlamydial therapy are indicated.

Anti-Bacterial Agents↗
PubMed1999

Clomipramine vs desipramine crossover trial in body dysmorphic disorder: selective efficacy of a serotonin reuptake inhibitor in imagined ugliness.

BACKGROUND: Body dysmorphic disorder (preoccupation with an imagined or slight defect in appearance) is a common and disabling disorder associated with high rates of delusional symptoms and suicide attempts. Although preliminary studies suggest that serotonin reuptake inhibitors may be effective for body dysmorphic disorder, to date no controlled treatment studies have been published. METHODS: Forty patients were enrolled and 29 were randomized into a 16-week, double-blind, crossover-design study of clomipramine, a potent serotonin reuptake inhibitor, and active control desipramine, a selective norepinephrine reuptake inhibitor. Outcome measures included specific ratings of body dysmorphic disorder severity, delusionality, and functional impairment. RESULTS: Clomipramine was superior to desipramine in the acute treatment of body dysmorphic disorder symptoms as measured by assessment of patients' obsessive preoccupation with perceived body defects, repetitive behaviors in response to this preoccupation, and global ratings of symptom severity. Treatment efficacy was independent of the presence or severity of comorbid diagnoses of obsessive-compulsive disorder, depression, or social phobia. Likewise, clomipramine was equally effective regardless of whether the patients had insight or held their dysmorphic misperception with delusional intensity. Clomipramine was also superior to desipramine in improving functional disability. CONCLUSIONS: Clomipramine is more effective than desipramine in the treatment of body dysmorphic disorder and is effective even among those patients who are delusional.

Adrenergic Uptake Inhibitors↗
PubMed1999

Systemic exposure to rosiglitazone is unaltered by food.

OBJECTIVE: To evaluate the effect of food on the bioavailability and pharmacokinetics of the insulin sensitizer rosiglitazone. METHODS: In a randomized, open-label, period-balanced, single-dose, crossover study, rosiglitazone 2 mg was administered to 12 healthy male volunteers either in the fasting state or following a standard high-fat breakfast. The primary end points of the study were AUC(0-inf) and Cmax. RESULTS: Single oral doses of rosiglitazone were safe and well tolerated. Overall exposure to rosiglitazone was unaffected by food. The geometric mean ratio of AUC(0-inf) in the fed:fasted regimens was 0.94 (95% CI: 0.82, 1.06); t1/2 was unaffected. Absorption of rosiglitazone in the fed state was more gradual and sustained than in the fasted state. Cmax was reduced by approximately 20% (point estimate 0.80; 95% CI 0.65 to 0.97) and tmax was modestly delayed in the fed state. CONCLUSION: These data support dosing guidelines that will permit the administration of rosiglitazone without regard to meals for treatment of type 2 diabetes mellitus.

Adolescent↗
PubMed1999

Development of a personal monitoring method for nitrogen dioxide and sulfur dioxide with Sep-Pak C18 cartridge sampling and ion chromatographic determination.

Personal monitoring methods for the determination of hourly integrated concentrations of NO2 and SO2 in ambient air have been developed. Triethanolamine (TEA)-impregnated C18 Sep-Pak cartridges were used to collect NO2 and SO2 simultaneously. After sampling, NO2 and SO2 as their nitrite, nitrate, sulfite and sulfate analogues were stripped from the cartridges with a solution of 5% methanol in distilled, deionized water (DDW) and then determined by ion chromatography. Laboratory tests were conducted to evaluate the sampling rate, collection and recovery efficiencies, breakthrough volumes, absorption capacity, interference and sample stability on the cartridge during storage. NO2 and SO2 detection limits of 0.3 and 0.4 ppb respectively for 1 h samples were obtained. Recoveries for both NO2 and SO2 exceeded 85%.

Air Pollutants↗
PubMed1999

Pigeon fanciers' lung: identification of disease-associated carbohydrate epitopes on pigeon intestinal mucin.

Pigeon intestinal mucin, a complex high molecular weight glycoprotein, is a key antigen in the development of pigeon fanciers' lung (PFL). We have studied the specificity of antibodies to mucin in patients with PFL and asymptomatic antibody-positive individuals. Extensive papain digestion, which removes the non-glycosylated regions of the mucin leaving the heavily glycosylated 'bottle brush' regions, resulted in a 600-fold decrease in IgG3 antibody titres with little effect on IgG1 and IgG2 titres. This suggests that IgG1 and IgG2 are directed against the region rich in O-linked sugar chains whilst the majority of the IgG3 is directed against epitopes which are proteinase-sensitive. Lectin mapping of the carbohydrates present on pigeon intestinal mucin demonstrated high levels of exposed N-acetyl neuraminic acid, N-acetyl galactosamine and N-acetyl glucosamine, with lower levels of fucose and some galactose. Sera from pigeon fanciers inhibited binding of lectins specific for N-acetyl neuraminic acid, N-acetyl galactosamine, internal N-acetyl glucosamine and fucose. Sera from people with PFL, compared with sera from asymptomatic antibody-positive fanciers, had significantly higher titres of antibody that inhibited binding of four lectins specific for N-acetyl galactosamine and one fucose-specific lectin, suggesting that these sugars may play a dominant role in disease-associated epitopes. The results suggest that different IgG subclasses recognize different epitopes on mucin and that the epitopes recognized by the major subclasses are present on the O-linked oligosaccharides. Further, the carbohydrate-specific anti-mucin antibodies produced by PFL patients may differ in their specificity from those found in asymptomatic individuals.

Animals↗