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Biomedical subjects

T Nicholls

Publications and source records attributed to T Nicholls.

At least 19 recordsLinked to original sources
PubMed2002

Treatment of constipation in adults associated with idiopathic megarectum by behavioural retraining including biofeedback.

BACKGROUND: Constipation in adults associated with a grossly dilated rectum and recurrent faecal impaction, idiopathic megarectum, is rare. The aetiology of idiopathic megarectum is unknown, but may involve neuromuscular or behavioural factors. It is unknown whether the condition is reversible. This study aimed to determine the efficacy of behavioural therapy, including biofeedback, in such patients. METHODS: Six patients (4 female; median age 27) with a history of rectal faecal impaction and a grossly dilated rectum on radiological examination were evaluated by structured questionnaire before, immediately after biofeedback therapy, and on follow-up. Physiological testing was performed before treatment, and 2 patients were evaluated by repeat physiological testing and contrast radiology on follow-up. RESULTS: On median follow-up of 18 months (range 11-27), five patients felt major and one patient minor improvement in symptoms, including two with complete symptom relief. Four patients came off laxatives without recurrent faecal impaction. In the 2 studied patients rectal size did not appear to decrease. CONCLUSION: Behavioural retraining, including biofeedback, improved symptoms in most patients with idiopathic megarectum. In some patients symptoms completely resolved, without the need for laxatives. Although further studies are necessary in terms of both larger number of patients and longer follow-up period, behavioural treatment may be useful for such patients.

Journal Article↗
PubMed2001

Endocoil magnetic resonance imaging quantification of external anal sphincter atrophy.

BACKGROUND: Anal function depends on the integrity and quality of the sphincter muscles. The diagnosis of external anal sphincter atrophy on endocoil magnetic resonography has been associated with poor outcome from sphincter repair, although the imaging criteria for atrophy remain unclear. METHODS: Women with intact sphincters on endosonography and either normal (more than 60 cm H(2)O) (n = 9) or low (n = 16) squeeze pressures had endocoil magnetic resonography and electromyography. The area and fat content of the external anal sphincter and puborectalis were measured on mid-coronal magnetic resonography and images were graded as showing normal, intermediate or advanced atrophy. The definition of the external anal sphincter on endosonography and the thickness of the internal anal sphincter were also assessed. RESULTS: Women with a normal anal squeeze pressure had a larger external anal sphincter cross-sectional area (mean(s.d.) 240(56) versus 193(62) mm(2); P = 0.01) with a lower mean fat content (mean(s.d.) 23(4) versus 30(6) per cent; P < 0.001) than those with low squeeze pressures. There was an overall correlation between squeeze pressure, cross-sectional area (r = 0.32, P = 0.02) and fat content (r = - 0.51, P < 0.001). Patients with a thin (less than 2 mm) internal anal sphincter and/or a poorly defined external sphincter on endosonography were more likely to have atrophy (positive predictive value 74 per cent). CONCLUSION: : Potential endosonographic markers for external anal sphincter atrophy are suggested, and a visual scale for endocoil magnetic resonographic assessment has been validated.

Adult↗
PubMed2001

Regional changes in kynurenic acid, quinolinic acid, and glial fibrillary acidic protein concentrations in the fetal sheep brain after experimentally induced placental insufficiency.

OBJECTIVE: This study was undertaken to examine the effects of chronic embolization of the umbilical circulation during late gestation on regional concentrations of quinolinic acid and kynurenic acid (neuroactive products of tryptophan catabolism) and of the astrocyte-associated glial fibrillary acidic protein in the fetal brain. STUDY DESIGN: Pregnant ewes bearing fetuses with long-term catheter placement were treated daily with injections of either saline solution (n = 4; control group) or mucopolysaccharide microspheres (n = 5; embolized group) into the umbilical circulation through a femoral artery catheter between 120 and 140 days' gestation. The fetuses in the embolized group received sufficient microspheres each day to reduce and maintain the femoral arterial PO2 at < or =12 mm Hg. Autopsies were performed at 140 days' gestation to obtain the fetal brain for chemical analysis. RESULTS: Umbilical embolization resulted in nonacidemic hypoxia and hypoglycemia at 140 days' gestation. Quinolinic acid concentrations in the embolized group were significantly increased in the medulla, pons, midbrain, hypothalamus, and hippocampus, whereas kynurenic acid concentrations in the embolized group were reduced in the hippocampus and hypothalamus. There were significant reductions in glial fibrillary acidic protein contents in the occipitoparietal cortex, hippocampus, and pons in the embolized group. CONCLUSION: Placental compromise during late pregnancy had effects on kynurenine metabolism and astrocyte function in some regions of the fetal sheep brain. We suggest that these changes increase the vulnerability of the brain to asphyxial injury during late gestation and the perinatal period.

Animals↗
PubMed2001

Kynurenine production and catabolism in fetal sheep with embolized or nonembolized placentas.

OBJECTIVE: The effect of maternal tryptophan loading on fetal plasma and brain, kynurenic acid, and quinolinic acid concentrations was compared in late gestation fetal sheep with either chronically embolized or nonembolized placentas. STUDY DESIGN: The placentas of 4 ewes were embolized by daily injection of mucopolysaccharide microspheres into the umbilical artery from 120 days gestation in amounts sufficient to reduce the fetal arterial PO2 to < or = 12 mm Hg. Four fetuses with nonembolized placentas were the control group. At 135 to 138 days gestation, the ewe received an infusion of tryptophan (100 mg/kg, intravenously) or an equivalent volume of saline solution (100 mL) over 2 hours. Maternal and fetal arterial blood samples were obtained between 2 and 48 hours from the start of the infusion for the measurement of plasma tryptophan and kynurenine metabolites. Brains were then obtained from embolized and nonembolized fetuses 24 hours after a further maternal tryptophan loading experiment and from nonembolized non-tryptophan-treated fetuses for analysis of regional kynurenic acid and quinolinic acid content. RESULTS: Maternal tryptophan infusion resulted in a significant increase of kynurenine in fetal plasma, but this increase was significantly smaller in fetuses with an embolized placenta compared with a nonembolized placenta. Both kynurenic acid and quinolinic acid levels increased significantly in fetal plasma, with no differences between the groups. Kynurenic acid and quinolinic acid levels were increased in all regions of the fetal brain after maternal tryptophan loading, but these increases were greater in the fetuses with an embolized placenta, compared with a nonembolized placenta. CONCLUSION: Fetal tryptophan and kynurenine metabolism is significantly altered when placental function is chronically compromised in late gestation. The decreased production of kynurenine from tryptophan may result from the compromise of hepatic function in the fetus, whereas the increased production of kynurenic acid and quinolinic acid in the brain is likely to reflect alterations of metabolism of tryptophan and kynurenine to these neuroactive products by glial cells in the fetal brain.

Animals↗
PubMed2001

Investigation of faecal incontinence.

Most patients with faecal incontinence require only a full history (information about other predisposing causes) and examination (assessment for faecal impaction and evaluation of sphincter function and structure). When necessary, anorectal physiological studies, endoanal ultrasound and magnetic resonance imaging allow accurate characterization of sphincter function and structure.

Endosonography↗
PubMed2001

Antimicrobial resistance: harmonisation of national antimicrobial resistance monitoring and surveillance programmes in animals and in animal-derived food.

A guideline on the harmonisation of national antimicrobial resistance monitoring and surveillance programmes in animals and animal-derived foods has been developed by the Ad hoc Group of experts on antimicrobial resistance of the Office International des Epizooties. The objective of the guideline is to allow the generation of comparable data from various national surveillance and monitoring systems in order to compare the situations in different regions or countries and to consolidate results at the national, regional and international level. Definitions of surveillance and monitoring are provided. National systems should be able to detect the emergence of resistance, and to determine the prevalence of resistant bacteria. The resulting data should be used in the assessment of risks to public health and should contribute to the establishment of a risk management policy. Specific factors identified for harmonisation include the animal species, food commodities, sampling plans, bacterial species, antimicrobials to be tested, laboratory methods, data reporting, database structure and the structure of reports.

Animals↗
PubMed2001

Antimicrobial resistance: standardisation and harmonisation of laboratory methodologies for the detection and quantification of antimicrobial resistance.

The Ad hoc Group of experts on antimicrobial resistance of the Office International des Epizooties has developed a guideline on the standardisation and harmonisation of laboratory methodologies used for the detection and quantification of antimicrobial resistance. The existing methods (disk diffusion [including concentration gradient strips], agar dilution and broth dilution) are reviewed, including a comparison of their advantages and disadvantages. The definitions of resistance characteristics of bacteria (susceptible, intermediate and resistant) are addressed and the criteria for the establishment of breakpoints are discussed. Due consideration has to be given to these aspects in the interpretation and comparison of resistance monitoring or surveillance data. The use of validated laboratory methods and the establishment of quality assurance (internal and external) for microbiological laboratory work and the reporting of quantitative test results is recommended. Equivalence of different methods and laboratory test results is also recommended to be established by external proficiency testing, which should be achieved by the means of a reference laboratory system. This approach allows the comparison of test results obtained using different methods generated by laboratories in different countries.

Animals↗
PubMed2001

Antimicrobial resistance: monitoring the quantities of antimicrobials used in animal husbandry.

This guideline, developed by the Office International des Epizooties for the monitoring of the quantities of antimicrobials used in animal husbandry, provides the methodology required to assess the amounts of antimicrobials used, to supply data to be used for risk analysis and to improve guidance on the appropriate use of antimicrobials. Information may be gathered from a number of sources, such as the competent authorities, industry and users. The usefulness of different types of information is discussed and recommendations are given on how to collect detailed information, each year, on the antimicrobial quantities used per class and active substance. Information should also be collected on the route of administration (oral and parenteral) and the animal species.

Animal Husbandry↗
PubMed2001

Antimicrobial resistance: responsible and prudent use of antimicrobial agents in veterinary medicine.

A guideline on the responsible and prudent use of antimicrobials in animal husbandry has been developed by the Ad hoc Group of experts on antimicrobial resistance, created by the Office International des Epizooties. The objectives of responsible use are to maintain antibiotic efficacy, to avoid the dissemination of resistant bacteria or resistance determinants and to avoid the exposure of humans to resistance through food. The guideline attributes a central role to the competent authorities responsible for granting marketing authorizations for antimicrobial substances. Requirements before and after granting of marketing authorizations are defined. Important aspects include the control of the pharmaceutical product quality and the therapeutic efficacy, the assessment of the selection pressure, the protection of the environment, specific and non-specific antimicrobial resistance surveillance. The guideline is also addressed to the veterinary pharmaceutical industry, veterinary practitioners, dispensing pharmacists and farmers. The respective roles and responsibilities of these groups are defined.

Animal Husbandry↗
PubMed2001

Antimicrobial resistance: risk analysis methodology for the potential impact on public health of antimicrobial resistant bacteria of animal origin.

The Ad hoc Group of experts on antimicrobial resistance, appointed by the Office International des Epizooties, has developed an objective, transparent and defensible risk analysis process, providing a valid basis for risk management decisions in respect to antimicrobial resistance. The components of risk analysis and of different possible approaches in risk assessment (qualitative, semiquantitative and quantitative) are defined. The Ad hoc Group recommended the following: an independent risk assessment based on scientific data; an iterative risk analysis process; a qualitative risk assessment systematically undertaken before considering a quantitative approach; the establishment of a risk assessment policy; and the availability of technical assistance for developing countries.

Animals↗
PubMed1999

Tryptophan metabolism in pregnant sheep: increased fetal kynurenine production in response to maternal tryptophan loading.

OBJECTIVE: The effects of a tryptophan load on the plasma concentration of kynurenine, the precursor for the production in the brain of the neuroactive products kynurenic acid and quinolinic acid, were determined in pregnant sheep at midgestation and late gestation and in nonpregnant sheep. STUDY DESIGN: Pregnant ewes were given an intravenous infusion of 100 mg/kg L-tryptophan during 2 hours at 95 to 98 days' gestation (n = 4) or 135 to 138 days' gestation (n = 10). Nonpregnant ewes (n = 6) were studied in late estrus. Arterial blood samples taken from 2 hours before to 48 hours after the start of the infusion were used for analysis of plasma tryptophan, kynurenine, and cortisol concentrations. RESULTS: Tryptophan loading at both gestational ages resulted in significantly greater increases in kynurenine concentrations in fetal plasma (at 95-98 days' gestation, from 5.7 +/- 1.2 micromol/L [baseline] to 247.9 +/- 86.7 micromol/L (peak); at 135-138 days' gestation, from 9.0 +/- 2.3 micromol/L [baseline] to 289.0 +/- 194.0 micromol/L [peak]) than in maternal plasma [at 95-98 days' gestation, from 4.6 +/- 0.8 micromol/L [baseline] to 118.0 +/- 79.7 micromol/L [peak]; at 135-138 days' gestation, from 4.8 +/- 2.9 micromol/L [baseline] to 98.3 +/- 67.8 micromol/L [peak]). It took longer for kynurenine concentrations to return to basal values in the fetus (24-30 hours) than in the ewe (8-12 hours). The kynurenine responses in pregnant and nonpregnant ewes were not different from each other. CONCLUSION: The production of kynurenine from tryptophan is significantly greater in the fetal lamb than in the pregnant or nonpregnant adult ewe.

Animals↗
PubMed1994

Praziquantel-induced exposure of Schistosoma mansoni alkaline phosphatase: drug-antibody synergy which acts preferentially against female worms.

The efficacy of praziquantel-treatment of murine Schistosoma mansoni-infections can be enhanced by concurrent administration of rabbit anti-sera with specificity for parasite antigens. Monospecific rabbit serum raised against S. mansoni worm alkaline phosphatase, that was reactive with the enzyme on the drug-treated female surface, was found to significantly and preferentially increase the mortality of female worms by PZQ. Immunoglobulins purified from the anti-alkaline phosphatase antiserum inhibited 54% of schistosome alkaline phosphatase enzymatic activity on the surface of praziquantel-treated worms. We propose that synergistic antibody-mediated death of drug-damaged worms is a consequence of the inhibition of drug-exposed alkaline phosphatase on the female worm surface by passively transferred antibody.

Alkaline Phosphatase↗