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Biomedical subjects

B Hunt

Publications and source records attributed to B Hunt.

At least 19 recordsLinked to original sources

Development of a real time PCR for the detection of Taylorella equigenitalis directly from genital swabs and discrimination from Taylorella asinigenitalis.

A discriminatory real time PCR for the detection of Taylorella equigenitalis, the causative agent of contagious equine metritis (CEM), and the related species T. asinigenitalis was developed for the direct examination of genital swabs. The 112bp amplicons produced from the two species were discriminated from each other using TaqMan probes labelled with different fluorophores. The TaqMan PCR was shown to be specific for the 16S ribosomal DNA of the two species of taylorella and did not cross-hybridise with the 16S ribosomal DNA of other bacteria tested. Direct amplification from genital swabs was shown to be equally sensitive to that of culture methods. Prevalence in a sample set from The Netherlands was shown to be equivalent to that demonstrated by culture. A companion real time PCR that amplified a fragment of the 16S rDNA gene of equine commensal bacteria was developed to ensure bacterial DNA was extracted from swab material supplied for testing. The use of a rapid and reliable real time PCR for the organism causing CEM should aid the control of this disease.

Animals↗

Dose-response evaluation of the antisecretory effect of continuous infusion intravenous lansoprazole regimens over 48 h.

BACKGROUND: Attainment of intragastric pH < 6.0 may require high-dose continuously infused proton pump therapy. AIM: To assess the pharmacokinetic and pharmacodynamic dose-responses of continuous infusion regimens of lansoprazole. METHODS: Healthy adult subjects were assigned to lansoprazole 60-mg intravenous bolus, followed by 6-mg/h continuous infusion; a 90-mg intravenous bolus followed by 6-, 7.5-, or 9-mg/h continuous infusion; or placebo. RESULTS: Mean intragastric pH values for lansoprazole regimens ranged from 4.8 to 5.2 (0-24 h), 5.5 to 6.0 (>24 to 48 h) and 5.2 to 5.6 (0-48 h). Within these three intervals, the percentages of time intragastric pH exceeded 4, 5 and 6 ranged from 65% to 96%, 54% to 88% and 30% to 61% respectively. Pharmacokinetic parameters were dose-independent with steady-state plasma concentrations achieved within 6-12 h postdose and maintained over 48 h. The mean systemic clearance of lansoprazole was lower in CYP2C19 heterozygous metabolizers than in homozygous extensive metabolizers (9.2 vs. 16.5 L/h), with substantial variability resulting in overlapping ranges of clearance values for both subpopulations. All lansoprazole regimens were well-tolerated. CONCLUSIONS: Lansoprazole administered as a 60-mg intravenous bolus followed by 6-mg/h continuous infusion produced intragastric pH effects comparable with those of higher dosage regimens.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Lansoprazole regimens that sustain intragastric pH > 6.0: an evaluation of intermittent oral and continuous intravenous infusion dosages.

BACKGROUND: Orally and intravenously administered proton pump inhibitors have been shown to reduce rebleeding rates, surgery and transfusion requirement. AIM: To compare lansoprazole intravenous and orally disintegrating tablet (Prevacid SoluTab) regimens with a pantoprazole intravenously administered regimen in sustaining intragastric pH >6.0. METHODS: Two similarly designed three-way, randomized crossover studies each enrolled 36 Helicobacter pylori-negative healthy volunteers. Study 1 regimens included intravenously administered bolus followed by 24-h continuous infusion (lansoprazole 90 mg, 6 mg/h; lansoprazole 120 mg, 6 mg/h; pantoprazole 80 mg, 8 mg/h). Study 2 regimens included intravenous bolus followed by lansoprazole orally disintegrating tablet or intravenous continuous infusion for 24 h (lansoprazole 90 mg, lansoprazole orally disintegrating tablet 60 mg every 6 h; lansoprazole 120 mg, 9 mg/h; pantoprazole 80 mg, 8 mg/h). Percentage of time pH >6.0 was assessed with 24-h intragastric pH monitoring. RESULTS: All regimens produced comparable gastric acid suppression. In both studies, regimens superior to pantoprazole included lansoprazole 90 mg, 6-mg/h; lansoprazole 90 mg, lansoprazole orally disintegrating tablet 60 mg q.d.s. and lansoprazole 120 mg, 9 mg/h (P < or = 0.013). The lansoprazole 120-mg, 6-mg/h regimen (P = 0.082) was not superior to pantoprazole in percentage of time intragastric pH >6.0. Mild reaction at the intravenous injection site was the most frequently reported adverse event. CONCLUSIONS: The intravenous bolus and continuously infused lansoprazole or intravenous bolus and intermittent lansoprazole orally disintegrating tablet regimens are as effective as intravenous pantoprazole in sustaining intragastric pH >6.0.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Clinical and pathological responses of weaned pigs to atmospheric ammonia and dust.

Nine hundred and sixty weaned pigs were exposed for five weeks to controlled concentrations of atmospheric ammonia and dust in a single, multifactorial experiment. The treatments were a mean dust concentration of either 1.2, 2.7, 5.1 or 9.9 mg/m3 (inhalable fraction) and a mean ammonia concentration of either 0.6, 10.0, 18.8 or 37.0 ppm, concentrations representative of commercial conditions. The experiment was carried out over two years and the pigs were used in eight batches, each consisting of five lots of 24 pigs. Each treatment combination was replicated once, and an additional control lot (nominally 0 mg/m3 dust and 0 ppm ammonia) was included in each batch. The dust concentration was the same in the other four lots in each batch in which the four concentrations of ammonia were used; thus, the split-plot design was more sensitive to the effects of ammonia than dust. The groups of pigs were kept separately in five rooms in a purpose-built facility, and the pollutants were injected continuously into the air supply. Ammonia was supplied from a pressurised cylinder, and the endogenous dust in each room was supplemented by an artificial dust manufactured from feed, barley straw and faeces, mixed by weight in the proportions 5:1:4; its ingredients were oven-dried, milled and mixed, and then resuspended in the air supply. The health of the pigs was assessed in terms of general pathology, respiratory tract pathology, and the microbiology of the nasal cavity, trachea and lung. In each batch, postmortem examinations were carried out on 40 pigs after five weeks' exposure to the pollutants and on 30 pigs two weeks later to test for carryover and recovery--a total of 560 pigs. These examinations revealed minimal gross pathology and widespread minor pathological changes of little significance. The pigs' turbinate and lung scores were low and unaffected by exposure to pollutants. All the putative bacterial pathogens, with the exception of toxigenic Pasteurella multocida type D, were isolated from the respiratory tract of the pigs of both ages, but there were no differences between the effects of the different concentrations of pollutants.

Air Pollutants↗

Pharmacogenomic assessment of treatment options in gestational diabetes.

Gene expression profiles offer a multidimensional view of metabolic diseases, typically characterized by a single parameter, and can provide a basis for choosing between therapies yielding a common clinical end point. We applied such an approach in gestational diabetes mellitus (GDM). Gene expression was examined in four maternal tissues and placentas from normal patients and euglycemic GDM patients, undergoing elective Cesarean sections at term, treated either by diet or diet plus insulin. Deviations from normal were 11-fold greater for the patients treated by diet, alone, than for patients treated by diet plus insulin. Assuming the achievement of a "normal" gene expression profile, in addition to euglycemia, is a desirable outcome of treatment, insulin treatment appears to have a beneficial effect in the treatment of GDM. Subsequently, we utilized the expression data to identify serum biomarkers that provide ways to monitor the benefits of insulin treatment in GDM.

Adipose Tissue↗

Febuxostat (TMX-67), a novel, non-purine, selective inhibitor of xanthine oxidase, is safe and decreases serum urate in healthy volunteers.

In order to evaluate the safety, pharmacological properties, and urate-lowering efficacy of febuxostat, a non-purine, selective inhibitor of xanthine oxidase, a Phase 1, 2-week, multiple-dose, placebo-controlled, dose-escalation study was conducted in 154 healthy adults of both sexes. Daily febuxostat doses in the range 10 mg to 120 mg resulted in proportional mean serum urate reductions ranging from 25% to 70% and in proportional increases in maximum febuxostat plasma concentrations and area under plasma concentration versus time curves. Accompanying the hypouricemic effect were increases in serum xanthine concentrations, decreases in urinary uric acid excretion, and increases in urinary xanthine and hypoxanthine excretion, confirming inhibition of xanthine oxidase activity by febuxostat. Hepatic conjugation and oxidative metabolism were the major pathways of elimination of febuxostat from the body, and renal elimination did not appear to play a significant role. Although not uncommon, adverse events were mild and self-limited, and no deaths or serious adverse events were observed. Febuxostat is a safe and potent hypouricemic agent in healthy humans.

Adult↗

Identification and distribution of a novel Malassezia species yeast on normal equine skin.

This study aimed to investigate the distribution of Malassezia species yeasts on the skin of healthy horses. Acetate tape samples were obtained from the lip, axilla, interbulbar region, groin and anus of 12 healthy horses. The samples were stained and examined microscopically and sites harbouring yeast-like organisms were identified. Contact plates were applied to the skin at these sites and cultured at 26 degrees C and 32 degrees C. No growth was obtained on horse blood, Sabouraud's dextrose or modified Dixon's agar. A pure growth of a Malassezia-type organism was obtained on Sabouraud's dextrose agar enriched with oleic acid when it was incubated at 30 degrees C. It was identified by 26S ribosomal DNA D1/D2 sequence analysis as a member of the genus Malassezia, and most closely related to Malassezia sympodialis. However, the level of sequence divergence indicated that it was a novel species.

Animals↗

Solutions and verification of a scale-dependent dispersion model.

In this paper, analytical solutions are derived for a one-dimensional scale-dependent dispersion model (SDM), considering linear equilibrium sorption and first-order degradation for continuous and pulse contaminant sources, with a constant input concentration in a semi-infinite uniform porous medium. In the SDM model, dispersivity alpha(x) is replaced with a constant epsilon multiplied by the transport distance x. The solution for a pulse source is verified experimentally in the analysis of tritium data obtained from an 8-m-long homogenous pea-gravel column with multiple sampling locations, and the results are compared with those analysed by a commonly used solution of a constant dispersion model (CDM). The SDM predicts concentrations satisfactorily at all sampling locations, while the CDM fits the experimental data well for only one location. Both models are then calibrated for each individual concentration breakthrough curve, using local values for either epsilon in the SDM or alpha(x) in the CDM. Both models give equally good fits for appropriate choices of individual epsilon and alpha(x) values, and both indicate a linear increase in alpha(x) with distance. The epsilon values tend to change little as x increases and are expected to approach a constant at relatively large distances downstream. Hence, predictions from the SDM should become more accurate as x increases.

Calibration↗

Rod influence on hue-scaling functions.

Rod influence on hue appearance of spectral lights was characterized by comparing the scaling of red, green, yellow, and blue hue sensations for an 8 degrees-diameter, 7 degrees-eccentric test spot under conditions that minimized (cone plateau) and maximized (dark adapted) rod influence at two mesopic light levels (1.5 and 3.0 log scoptic trolands). At the lower light level, the hue-scaling functions showed that rod signals influenced the spectral range and magnitude of all four primary hues. The rod influence could not be characterized as a ubiquitous augmentation or diminution of any hue over the entire spectrum. This constrains models of rod influence on color vision.

Adult↗

Emphasizing terminal care as district nursing work: a helpful strategy in a purchasing environment?

This paper describes how within a study on the experiences of district nurses since the introduction of general practitioner purchasing, participants were encouraged to describe and define the district nursing service. The identification of terminal care by district nurses and others as a significant and defining example of district nursing work is explored and the possible reasons for its emphasis over other aspects of patient care. The extent to which terminal care was used within contract and purchasing discussions to aid general practitioner understanding of district nursing work and achieve extra funding is described. The paper concludes by questioning the extent to which terminal care is a helpful and accurate representation of what district nursing work entails, and the implications there may be in emphasizing one aspect of care within a purchasing environment.

Community Health Nursing↗

Otitis in a weaned pig: a new pathological role for Actinobacillus (Haemophilus) pleuropneumoniae.

A weaned pig exhibiting clinical signs characteristic of a vestibular syndrome (abnormal head tilt and abnormal gait including a tendency to circle) was examined as a representative example of a condition which, in a 12-month period, affected approximately 400 other pigs on the farm of origin. The condition caused significant morbidity and financial loss but the directly attributable mortality was negligible. Post mortem examination revealed a severe suppurative, left-sided otitis media and interna. Mixed growths of bacteria, including Actinobacillus pleuropneumoniae, were isolated from the pus from the middle ear. Otitis caused by mixed bacterial infections has been described previously in pigs and cattle but infection of the porcine middle ear cavity by A pleuropneumoniae is considered to be a new pathological role for this organism. Other findings in this case indicated that otitis media had followed from bacterial colonisation of the auditory (Eustachian) tube. The condition was effectively controlled by prophylactic antibiotic therapy. The authors consider that vestibular syndrome due to otitis media and interna, whether caused by infection with A pleuropneumoniae or not, is probably a relatively common condition in England but its significance may be underestimated and for this reason it may be underrecorded.

Actinobacillus Infections↗

Assessing the side-effects of antipsychotic drugs: a survey of CPN practice.

The provision of community-based care for people with serious and enduring mental health problems requires an approach that combines drug therapy, psychological interventions and skills training. Mental health nurses are being required to place more emphasis on their work with this client group. It has been suggested that community psychiatric nurses (CPNs) will require training in appropriate skills to work with the seriously mentally ill. While the training of CPNs to use psychological intervention strategies has received limited attention, the area of medication management, including the detection of side-effects, is relatively unexplored. Community psychiatric nurses' practice with clients on antipsychotic medication was investigated. This paper reports selected findings on the assessment of medication side-effects and CPNs' attitude to this aspect of their role. Fifty CPNs in three health districts completed a self-administered questionnaire. The results showed that the CPNs were supervising the medication of large numbers of clients. They reported that their training had adequately prepared them to assess clients for medication side-effects and that this was being done frequently. They also felt that their reports of side-effects influence the prescribers' decisions on medication when clients are reviewed. However, the data also suggested that CPNs were only monitoring their clients for three to four side-effects and that they held an unfavourable attitude towards their involvement with medication.

Antipsychotic Agents↗

Mechanisms of thrombin generation during surgery and cardiopulmonary bypass.

Although in vitro studies have been invaluable in revealing the complex biochemistry of the blood coagulation system, the mechanisms involved during the in vivo response to hypercoagulable stimuli are still unclear. We have used plasma-based enzyme-linked immunosorbent assays (ELISAs) to study the mechanisms by which the coagulation system is activated in vivo during human cardiopulmonary bypass (CPB) surgery (n = 8). A novel immunoassay for factor XIIa was used to detect activation of the contact system, factor IX activation peptide (FIXAP) was used as a marker for activation of factor IX, and prothrombin fragment F1 + 2 (F1 + 2) was used as a marker for thrombin generation. The ELISA for FIXAP is described for the first time herein. F1 + 2 levels increased early in response to surgical intervention: from a baseline of 38.7 +/- 9.7 ng/mL (mean +/-SE), levels increased rapidly during surgery and bypass to a maximum of 448.5 +/- 92.0 ng/mL. A modest yet significant increase in factor XIIa levels from 3.47 +/- 0.54 ng/mL to 4.33 +/- 0.85 ng/mL was evident during surgery before bypass, but no further significant increase was detected on establishing extracorporeal circulation. FIXAP levels demonstrated a small and late increase during surgery from 4.98 +/- 0.55 ng/mL to a maximum of 10.20 +/- 1.23 ng/mL, the increase beginning at the time of near maximal F1 + 2 levels. There was no association between activation of the contact system (factor XIIa levels) and the generation of thrombin (F1 + 2 levels). However, a strong association (r = .705) was apparent between the generation of thrombin (F1 + 2 levels) and activation of factor IX (FIXAP levels), despite the delay between the activation of prothrombin and factor IX. The data do not support the established view that contact activation resulting from exposure of blood to foreign surfaces is the major procoagulant stimulus in CPB. Instead, the results suggest that the main trigger to coagulation during CPB surgery was provided via the tissue factor-factor VIIa mechanism in response to the cutting of blood vessels, which directly activated factor X and then prothrombin. The late activation of factor IX, which presumably also contributed to maximal prothrombin activation, could have arisen due to direct tissue factor-factor VIIa action, or by secondary feedback action of thrombin on the intrinsic system.

Aged↗

Thrombin production, inactivation and expression during open heart surgery measured by assays for activation fragments including a new ELISA for prothrombin fragment F1 + 2.

Activation of coagulation was studied during the peri-operative period in patients undergoing cardiopulmonary bypass (CPB) surgery using activation markers which have recently become available: prothrombin fragment F1 + 2 (F1 + 2), which is a measure of total thrombin generation, and thrombin-antithrombin complex, which is a measure of inactivation of free thrombin by antithrombin. Levels of the specific marker of fibrin breakdown, D-dimer, were also determined. F1 + 2 levels were assessed using a newly developed ELISA described herein which employs a neoantigen-specific capture antibody raised using a synthetic peptide; the latter antibody has been pre-adsorbed against prothrombin to ensure high specificity for F1 + 2. Increased generation of thrombin during surgery was clearly demonstrated despite maintenance of a high concentration of heparin during the period of extracorporeal blood circulation. There was a close association (r = 0.882) between the generation of thrombin (F1 + 2 levels) and its inhibition (TAT levels). Differences were noted, however, between the information provided by F1 + 2 and TAT, which are interpreted with regard to the different in vivo fates of F1 + 2 and thrombin. The enhanced activation and inhibition of coagulation observed during CPB was suppressed once physiological blood circulation was restored, with F1 + 2 returning to pre-surgical levels within 24 h after surgery. During the post-operative period D-dimer levels, which rose in concert with F1 + 2 and TAT levels, remained highly elevated, suggesting that not all of the generated thrombin was inactivated by antithrombin.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗