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Biomedical subjects

M A Chapman

Publications and source records attributed to M A Chapman.

At least 19 recordsLinked to original sources
PubMed2001

Decreased choline acetyltransferase immunoreactivity in discrete striatal subregions following chronic haloperidol in rats.

Neuronal loss within the basal ganglia has been hypothesized to play a role in movement disorders (e.g., tardive dyskinesia) that often occur following chronic neuroleptic treatment. Previous studies in animal models have provided some support to this possibility, but have not assessed regionally specific changes after chronic neuroleptic administration. The present study examined whether counts of neurons containing acetylcholine, described as large aspiny type II neurons, were altered in subregions of the corpus striatum and nucleus accumbens following chronic haloperidol administration in rats. Rats were administered haloperidol decanoate (21 mg/kg, i.m.) or vehicle every third week for 24 weeks. Following 4 weeks of withdrawal from the drug, predefined regions were examined for choline acetyltransferase (ChAT) immunoreactive (ir) cells. Compared to the vehicle group, the haloperidol group showed significant reductions in ChAT-ir cell counts in the ventrolateral striatum, nucleus accumbens core, and nucleus accumbens lateral shell. No significant differences were found in the other regions examined: dorsolateral striatum, dorsomedial striatum, ventromedial striatum, nucleus accumbens medial shell, and horizontal limb of the diagonal band. These findings indicate that there may be regionally specific alterations in ChAT-ir cells following chronic haloperidol treatment, supporting previous hypotheses of striatal cholinergic cell loss resulting from chronic neuroleptic treatment. More importantly, the regions affected (ventrolateral striatum and nucleus accumbens) are critical in the regulation of oral movements, thus suggesting that alterations in cholinergic cell activity, and perhaps actual loss of cholinergic cells in these regions, may be important in the manifestation of late-onset oral dyskinesia.

Acetylcholine↗
PubMed2001

The role of the colonic flora in maintaining a healthy large bowel mucosa.

This work explores the intricate relationships between bacterial products of fermentation, the short chain fatty acids and the effect that these have on the colonic epithelium and the immune system. It confirms that butyrate is a major energy source for the colonic epithelium and there may be a minor epithelial abnormality in the metabolism of butyrate in patients with ulcerative colitis. Immunological studies suggest that butyrate has an effect on lymphocyte activation and inhibits cell proliferation. Possibly, butyrate induces anergy in lymphocytes via an effect on the TCR receptor. This may represent a mechanism whereby colonic bacteria are able to regulate the host immune response. An abnormal response to butyrate may upset the homeostasis between the gut immune system and the colonising bacteria resulting in epithelial unrest and inflammation.

Adult↗
PubMed2000

In vivo measurement of colonic butyrate metabolism in patients with quiescent ulcerative colitis.

BACKGROUND: Butyrate, a short chain fatty acid produced by bacterial fermentation, is a major fuel source for the colonocyte. In vitro work has shown that ulcerative colitis may be characterised by a metabolic defect in colonocyte butyrate oxidation. AIMS: To investigate the rate of metabolism of rectally administered butyrate in patients with quiescent colitis. METHODS: [1-(13)C]-butyrate enemas were administered to 11 patients with long standing quiescent ulcerative colitis and to 10 control patients. The rate of production of (13)CO(2) in exhaled breath over four hours was measured by isotope ratio mass spectrometry combined with indirect calorimetry in order to measure CO(2) production. This allowed calculation of the patients' resting energy expenditure and respiratory quotient. RESULTS: Over a four hour period, 325 (SEM 21) micromol (13)CO(2) was recovered in breath samples from the colitis group compared with 322 (17) micromol from the control group (NS). The respiratory quotient of the colitic group was significantly lower than that of the control group. CONCLUSION: There was no difference in the rate of metabolism of butyrate between the two groups. It is unlikely that there is a primary metabolic defect of butyrate metabolism in patients with quiescent ulcerative colitis.

Adult↗
PubMed1999

Exercise-induced hypoxaemia in highly trained cyclists at 40% peak oxygen uptake.

A group of 15 competitive male cyclists [mean peak oxygen uptake, VO2peak 68.5 (SEM 1.5 ml x kg(-1) x min(-1))] exercised on a cycle ergometer in a protocol which began at an intensity of 150 W and was increased by 25 W every 2 min until the subject was exhausted. Blood samples were taken from the radial artery at the end of each exercise intensity to determine the partial pressures of blood gases and oxyhaemoglobin saturation (SaO2), with all values corrected for rectal temperature. The SaO2 was also monitored continuously by ear oximetry. A significant decrease in the partial pressure of oxygen in arterial blood (PaO2) was seen at the first exercise intensity (150 W, about 40% VO2peak). A further significant decrease in PaO2 occurred at 200 W, whereafter it remained stable but still significantly below the values at rest, with the lowest value being measured at 350 W [87.0 (SEM 1.9) mmHg]. The partial pressure of carbon dioxide in arterial blood (PaCO2) was unchanged up to an exercise intensity of 250 W whereafter it exhibited a significant downward trend to reach its lowest value at an exercise intensity of 375 W [34.5 (SEM 0.5) mmHg]. During both the first (150 W) and final exercise intensities (VO2peak) PaO2 was correlated significantly with both partial pressure of oxygen in alveolar gas (P(A)O2, r = 0.81 and r = 0.70, respectively) and alveolar-arterial difference in oxygen partial pressure (P(A-a)O2, r = 0.63 and r = 0.86, respectively) but not with PaCO2. At VO2peak PaO2 was significantly correlated with the ventilatory equivalents for both oxygen uptake and carbon dioxide output (r = 0.58 and r = 0.53, respectively). When both P(A)O2 and P(A-a)O2 were combined in a multiple linear regression model, at least 95% of the variance in PaO2 could be explained at both 150 W and VO2peak. A significant downward trend in SaO2 was seen with increasing exercise intensity with the lowest value at 375 W [94.6 (SEM 0.3)%]. Oximetry estimates of SaO2 were significantly higher than blood measurements at all times throughout exercise and no significant decrease from rest was seen until 350 W. The significant correlations between PaO2 and P(A)O2 with the first exercise intensity and at VO2peak led to the conclusion that inadequate hyperventilation is a major contributor to exercise-induced hypoxaemia.

Adult↗
PubMed1999

Joint surface modeling with thin-plate splines.

Mathematical joint surface models based on experimentally determined data points can be used to investigate joint characteristics such as curvature, congruency, cartilage thickness, joint contact areas, as well as to provide geometric information well suited for finite element analysis. Commonly, surface modeling methods are based on B-splines, which involve tensor products. These methods have had success; however, they are limited due to the complex organizational aspect of working with surface patches, and modeling unordered, scattered experimental data points. An alternative method for mathematical joint surface modeling is presented based on the thin-plate spline (TPS). It has the advantage that it does not involve surface patches, and can model scattered data points without experimental data preparation. An analytical surface was developed and modeled with the TPS to quantify its interpolating and smoothing characteristics. Some limitations of the TPS include discontinuity of curvature at exactly the experimental surface data points, and numerical problems dealing with data sets in excess of 2000 points. However, suggestions for overcoming these limitations are presented. Testing the TPS with real experimental data, the patellofemoral joint of a cat was measured with multistation digital photogrammetry and modeled using the TPS to determine cartilage thicknesses and surface curvature. The cartilage thickness distribution ranged between 100 to 550 microns on the patella, and 100 to 300 microns on the femur. It was found that the TPS was an effective tool for modeling joint surfaces because no preparation of the experimental data points was necessary, and the resulting unique function representing the entire surface does not involve surface patches. A detailed algorithm is presented for implementation of the TPS.

Algorithms↗
PubMed1999

Precise measurement of cat patellofemoral joint surface geometry with multistation digital photogrammetry.

Three-dimensional joint models are important tools for investigating mechanisms related to normal and pathological joints. Often these models necessitate accurate three-dimensional joint surface geometric data so that reliable model results can be obtained; however, in models based on small joints, this is often problematic due to limitations of the present techniques. These limitations include insufficient measurement precision the requirement of contact for the measurement process, and lack of entire joint description. This study presents a new non-contact method for precise determination of entire joint surfaces using multistation digital photogrammetry (MDPG) and is demonstrated by determining the cartilage and subchondral bone surfaces of the cat patellofemoral (PF) joint. The digital camera-lens setup was precisely calibrated using 16 photographs arranged to achieve highly convergent geometry to estimate interior and distortion parameters of the camera-lens setup. Subsequently, six photographs of each joint surface were then acquired for surface measurement. The digital images were directly imported to a computer and newly introduced semi-automatic computer algorithms were used to precisely determine the image coordinates. Finally, a rigorous mathematical procedure named the bundle adjustment was used to determine the three-dimensional coordinates of the joint surfaces and to estimate the precision of the coordinates. These estimations were validated by comparing the MDPG measurements of a cylinder and plane to an analytical model. The joint surfaces were successfully measured using the MDPG method with mean precision estimates in the least favorable coordinate direction being 10.3 microns for subchondral bone and 17.9 microns for cartilage. The difference in measurement precision for bone and cartilage primarily reflects differences in the translucent properties of the surfaces.

Algorithms↗
PubMed1998

Preoperative carcinoembryonic antigen is related to tumour stage and long-term survival in colorectal cancer.

Evidence as to the value of preoperative carcinoembryonic antigen (CEA) in guiding treatment for patients with colorectal cancer is conflicting. The aim of this prospective study was to investigate the value of preoperative CEA in predicting tumour factors of proven prognostic value and long-term survival in patients undergoing surgery for colorectal cancer. Preoperative serum CEA, tumour ploidy, stage and grade were ascertained in 277 patients undergoing colorectal cancer surgery. This cohort of patients were followed up for a minimum of 5 years, or until death, in a dedicated colorectal clinic. Patients with an elevated CEA had a 5 year survival of 39%. This increased to 57% if the CEA was normal (P=0.001). The proportion of patients with a raised CEA increased with a more advanced tumour stage (P < 0.000001) and a poorly differentiated tumour grade (P < 0.005). Once stage had been controlled for, CEA was not a predictor of survival. No relationship between tumour ploidy and CEA was found. In conclusion, a raised preoperative serum CEA is likely to be associated with advanced tumour stage and poor long-term survival, compared with patients with a normal value.

Adult↗
PubMed1997

Metabolic adaptation of terminal ileal mucosa after construction of an ileoanal pouch.

BACKGROUND: The major nutrients for the large bowel and small bowel mucosa are, respectively, butyrate and glutamine. The degree of mucosal adaptation that may occur in response to changes in nutrient supply and faecal stasis after the formation of an ileoanal pouch is poorly understood. METHOD: The ability of ileal mucosal biopsies, from nine patients with ulcerative colitis and from 18 with an ileoanal pouch, to oxidize [14C]-glucose, glutamine and butyrate to carbon dioxide was quantified. RESULTS: Glucose, glutamine and butyrate were oxidized respectively at a median of 12.5 (95 per cent confidence interval (4-22), 77 (34-207) and 194 (81-321) pmol microgram-1 h-1 by ileal mucosa and 12.9 (6-21), 35 (11-57) and 194 (73-737) pmol microgram-1 h-1 by pouch mucosa. CONCLUSION: Ileoanal pouch construction and subsequent bacterial colonization and faecal stasis resulted in a significant (P < 0.05) reduction in the mucosal ability to oxidize glutamine whereas there was no difference in the rate of butyrate oxidation.

Adult↗
PubMed1996

Altered Fos-like immunoreactivity in terminal regions of the mesotelencephalic dopamine system is associated with reappearance of tyrosine hydroxylase immunoreactivity at the sites of focal 6-hydroxydopamine lesions in the nucleus accumbens.

The present study was undertaken in order to determine whether unilateral 6-hydroxydopamine (6-OHDA) lesions in the nucleus accumbens (Acb) affect basal Fos-like immunoreactivity (-LI) in terminal regions of the mesotelencephalic dopamine system. It was hypothesized that dopamine depletion in the Acb would alter activation of mesotelencephalic dopamine neurons perhaps via the striatomesencephalic GABAergic pathway, and that this may be detected as altered basal Fos-LI in mesotelencephalic terminal regions. 6-OHDA treatment effectively depleted tyrosine hydroxylase (TH)-LI in well-circumscribed areas of the Acb at 14 days post-lesion, but at 25 days post-lesion all animals showed a reappearance of TH-LI staining in the lesioned region. When data from a number of mesotelencephalic terminals regions was pooled. Fos-LI cell density was higher in the sham and lesion 14-day groups and sham 25-day group than both the 25-day lesion group and untreated controls. The present study demonstrates that unilateral sham and 6-OHDA lesions in the Acb may have repercussions throughout the mesotelencephalic dopamine system. Further investigation is necessary to determine whether reappearance of TH-LI at the lesion site contributes to the return of Fos-LI to basal levels.

Animals↗
PubMed1996

The neurotensin receptor antagonist SR 48692 decreases extracellular striatal GABA in rats.

Intracranial microdialysis was utilized to assess the effects of the novel neurotensin antagonist SR 48692 on extracellular gamma-amino-butyric acid (GABA) and glycine in the striatum. Subcutaneous injection of SR 48692 (0.2 mg/kg) significantly decreased extracellular striatal GABA levels, with peak decreases occurring 2-3 h post-injection. Injection of SR 48692 had no significant effect on glycine levels. These data suggest that endogenous neurotensin may modulate striatal GABA levels.

Analysis of Variance↗
PubMed1996

Differential effects of unique profile antipsychotic drugs on extracellular amino acids in the ventral pallidum and globus pallidus of rats.

The effects of antipsychotic drugs (APDs) on brain dopamine receptors in the striatum are ultimately expressed through efferent projections which primarily use amino acid transmitters, including gamma-aminobutyric acid and glutamate. The present study examined the effects of APDs on extracellular amino acid levels in the rat ventral pallidum (VP) and globus pallidus (GP), areas that receive projections from distinct striatal subregions. Clozapine, an APD with low motor side effect liability, and metoclopramide, a low-potency APD with high motor side effect liability, were compared with haloperidol, a widely used APD with high motor side effect liability. Drugs were administered subcutaneously and amino acid levels were monitored concurrently in the VP and GP by intracranial microdialysis. High doses of haloperidol and metoclopramide increased and clozapine decreased extracellular gamma-aminobutyric acid levels in the GP but not the VP. Low, but not high, doses of the three drugs tended to increase extracellular glutamate levels in both pallidal regions. Clozapine, but not the other two drugs, decreased extracellular threonine in the GP and glycine and threonine in the VP. Results indicate a correlation between increased gamma-aminobutyric acid levels in the GP and the propensity of the APDs tested to induce motor side effects. The novel effects of clozapine on extracellular glycine and threonine further distinguish this drug as a unique antipsychotic compound.

Amino Acids↗
PubMed1995

Five-year prospective study of DNA tumor ploidy and colorectal cancer survival.

BACKGROUND: Retrospective studies have suggested that DNA tumor content (ploidy) has a significant effect on survival. This group has reported, prospectively, that among patients who had colorectal resections for carcinoma, the 2-year tumor recurrence rate was significantly greater for patients with aneuploid tumor than for those with diploid tumors. This paper reports the 5-year survival rates of this cohort of patients. METHODS: Three hundred sixty-three patients who had colorectal resections for cancer between November, 1982, and March, 1988, were studied prospectively. The DNA tumor ploidy was measured from fresh and paraffin embedded tissues. These patients were followed regularly in a dedicated colorectal clinic for a minimum of 5 years or until death. Of the 363 patients studied, 2 were lost to follow-up. RESULTS: Forty percent of the tumors were diploid, the remainder aneuploid. The 5-year survival for patients who had curative resections was 76% for those with diploid tumors compared with 64% for aneuploid tumors (P = 0.05; Mantel-Cox, 3.7). On further analysis, the survival benefit conferred by a diploid tumor appeared to be confined to those with Stage B tumors. There was no relation between ploidy and sex, age of patient, stage, histologic grade, or site of tumor. CONCLUSIONS: Ploidy is a useful objective measurement of the aggressiveness of Stage B tumors. Patients with aneuploid Stage B tumors have a poor prognosis; this group may benefit from adjuvant therapy.

Adult↗
PubMed1995

Butyrate metabolism in the terminal ileal mucosa of patients with ulcerative colitis.

The rate of oxidation of butyrate, glutamine and glucose was investigated in terminal ileal mucosal biopsy samples from nine patients with ulcerative colitis undergoing restorative proctocolectomy and from 12 patients undergoing laparotomy for reasons other than ulcerative colitis. Substrate oxidation was assayed using a radiolabelled isotope technique. Butyrate was the preferred fuel substrate, followed by glutamine and then glucose (median (95 per cent confidence interval) 567 (262-894), 63 (35-123) and 8.1 (5.1-18) pmol micrograms-1 h-1 respectively; P < 0.01, Mann-Whitney U test) in normal terminal ileal mucosa. The patients with ulcerative colitis had a significantly reduced rate of butyrate oxidation compared with the control group (194 (81-321) versus 567 (262-894) pmol micrograms-1 h-1, P < 0.05). Normal terminal ileal mucosa oxidized butyrate in greater quantities than glucose and glutamine. Ulcerative colitic terminal ileal mucosa exhibited an impaired rate of butyrate oxidation.

Adolescent↗
PubMed1995

Complications of the ileal pouch: is the pouchogram a useful predictor?

A series of ileal pouchograms from 25 consecutive patients has been analysed retrospectively. Ileal pouchography may demonstrate abnormalities which delay closure of the covering ileostomy. The aim was to determine whether disruption of the ileoanal anastomosis and/or leak at pouchography correlated with pelvic sepsis after ileostomy closure. Disruption of the stapled ileoanal anastomosis is a sensitive (88%) but not specific predictor (57%) for subsequent pelvic sepsis. The predictive value of a negative test is high (89%). Leak of contrast from the anastomosis is specific (81%) but not sensitive (56%) for pelvic sepsis. No significant relationship was demonstrated between width of the presacral space and the presence of pelvic sepsis. No significant relationship was demonstrated between diameter of the ileoanal anastomosis and symptoms of stricture. The presence of anastomotic disruption or leak at pouchography prior to ileostomy closure are useful predictors of potential pelvic sepsis.

Adolescent↗
PubMed1994

Chronic haloperidol, but not clozapine, produces altered oral movements and increased extracellular glutamate in rats.

Rats administered chronic haloperidol or clozapine in their drinking water for 6 months were monitored for changes in oral movements using a computerized video analysis system. Haloperidol-treated animals exhibited late onset increases in small amplitude oral movements and an increase in the percentage of oral movements in the 1-2 Hz range, accompanied by a decrease in oral movements in the higher frequency range (> 6 Hz) as determined by fast fourier analysis. In contrast, clozapine-treated rats showed a decrease in medium-sized amplitude oral movements, but did not demonstrate significant changes in the distribution of oral movements across frequencies. Extracellular concentrations of gamma-aminobutyric acid (GABA) and glutamate in the ventrolateral striatum were then assessed by intracranial microdialysis during oral drug administration and 3 days after drug withdrawal. Extracellular GABA and glutamate levels were not significantly different between groups during drug administration. However, 3 days after drug withdrawal, there was a significant increase in glutamate in the haloperidol-treated rats. No changes were noted for glutamate levels in clozapine-treated rats or for GABA levels in either group following withdrawal. These results confirm the atypical profile of clozapine in an animal model of tardive dyskinesia and suggest that alterations in striatal glutamatergic function follow typical, but not atypical, antipsychotic drug administration.

Administration, Oral↗
PubMed1994

Butyrate oxidation is impaired in the colonic mucosa of sufferers of quiescent ulcerative colitis.

The short chain fatty acids, acetate, propionate, and butyrate are produced by colonic bacterial fermentation of non-starch polysaccharides. Butyrate is the major fuel source for the colonic epithelium and there is evidence to suggest that its oxidation is impaired in ulcerative colitis. Triplicate biopsy specimens were taken at colonoscopy from five regions of the large bowel in 15 sufferers of ulcerative colitis. These patients all had mild or quiescent colitis as assessed by clinical condition, mucosal endoscopic and histological appearance. The rate of oxidation of glucose, glutamine, and butyrate through to carbon dioxide was compared with that in biopsy specimens from 28 patients who had no mucosal abnormality. Butyrate (272 (199-368)) was the preferred fuel source for the colitic mucosa followed by glutamine (33 (24-62)) then glucose (7.2 (5.3-15)) pmol/micrograms/hour; medians and 95% confidence intervals, p < 0.01. There was no regional difference in the rate of utilisation of these metabolites. In the group with colitis the rate of butyrate oxidation to carbon dioxide was significantly impaired compared with that in normal mucosa decreasing from 472 (351-637) pmol/micrograms/hour to 272 (199-368) pmol/micrograms/hour; median and 95% confidence intervals, p = 0.016. The rate of glucose and glutamine utilisation were not significantly different between normal and colitic mucosa. These data confirm that in quiescent ulcerative colitis there is an impairment of butyrate oxidation.

Adult↗