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Biomedical subjects

A Anthony

Publications and source records attributed to A Anthony.

At least 37 records · Page 2Linked to original sources
PubMed1999

The colonic mesenteric margin is most susceptible to injury in an experimental model of colonic ulceration.

BACKGROUND: Crohn's disease ileal ulcers and indomethacin-induced jejunal ulceration in the rat tend to occur in the mucosa nearest to the mesentery (mesenteric margin), an area of the bowel wall that has a critical blood supply. Mercuric chloride induces caecal and colonic ulceration in the Brown Norway rat. AIM: To examine whether the mesenteric margin is more sensitive to injury by a substance known to be vasculotoxic in the caecum and colon. METHODS: Brown Norway rats received a single subcutaneous dose of either mercuric chloride 1 mg/kg or saline. The gastrointestinal tract was examined macro- and microscopically for lesions 48 h later. The vascular anatomy of the normal rat colon and caecum was also examined using the carbon ink perfusion technique. RESULTS: Mercuric chloride induced caecal and colonic ulceration preferentially along the mesenteric margin of the bowel wall. Histologically, the lesions showed mucosal necrosis and neutrophil infiltration. There was also extensive vascular degeneration/necrosis with microaneurysm formation and extensive submucosal haemorrhage. Cellular infiltration of the vasculature was not a feature. The caecal and colonic mesenteric margins in control rats were supplied by small end arteries. CONCLUSIONS: The colonic and caecal mesenteric margins are susceptible to injury by mercuric chloride, a chemical known to induce haemorrhagic vasculopathy in the rat gastrointestinal tract. The large bowel mesenteric margin may be susceptible to injury by mercuric chloride because of the critical blood supply to that side of the bowel wall.

Animals↗
PubMed1998

Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children.

BACKGROUND: We investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder. METHODS: 12 children (mean age 6 years [range 3-10], 11 boys) were referred to a paediatric gastroenterology unit with a history of normal development followed by loss of acquired skills, including language, together with diarrhoea and abdominal pain. Children underwent gastroenterological, neurological, and developmental assessment and review of developmental records. Ileocolonoscopy and biopsy sampling, magnetic-resonance imaging (MRI), electroencephalography (EEG), and lumbar puncture were done under sedation. Barium follow-through radiography was done where possible. Biochemical, haematological, and immunological profiles were examined. FINDINGS: Onset of behavioural symptoms was associated, by the parents, with measles, mumps, and rubella vaccination in eight of the 12 children, with measles infection in one child, and otitis media in another. All 12 children had intestinal abnormalities, ranging from lymphoid nodular hyperplasia to aphthoid ulceration. Histology showed patchy chronic inflammation in the colon in 11 children and reactive ileal lymphoid hyperplasia in seven, but no granulomas. Behavioural disorders included autism (nine), disintegrative psychosis (one), and possible postviral or vaccinal encephalitis (two). There were no focal neurological abnormalities and MRI and EEG tests were normal. Abnormal laboratory results were significantly raised urinary methylmalonic acid compared with age-matched controls (p=0.003), low haemoglobin in four children, and a low serum IgA in four children. INTERPRETATION: We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers.

Child↗
PubMed1998

Manipulation for cervical spinal dislocation under general anaesthesia: serial review for 4 years.

Manipulation under anaesthesia is an important method to reduce cervical spinal dislocations in the acute stage. Causes of failure have not been clearly identified and neurological complications can be the major concern. All cervical dislocations have been traditionally treated by manipulation under anaesthesia in the Christchurch Spinal Injuries Unit as the primary treatment. We reviewed all 31 patients treated from 1991-1995, with detailed documentation of neurological progression and final outcome. Three patterns were identified: bilateral dislocation, unifacet dislocation and fracture dislocation. Most of the dislocations (74%) were successfully reduced by manipulation alone with minimum complications. The remaining 26% patients required open reduction. The predominant causes of failure of reduction by manipulation were co-existing fractures. The success rate of reduction by manipulation was 90% for pure bifacet and unifacet dislocations, but was only 22% for the fracture dislocations. The study concluded that manipulation under anaesthesia is a safe and effective procedure for pure cervical spinal dislocations. Fractures related to the dislocation should be identified early and open reduction be considered.

Adolescent↗
PubMed1998

Localization of the beta(beta)3-adrenoceptor in the human gastrointestinal tract: an immunohistochemical study.

BACKGROUND: Activation of human and non-human colonic beta(beta)3-adrenoceptors causes smooth muscle relaxation. beta3-Adrenoceptor agonists protect against experimental indomethacin-induced jejunal ulceration. The mechanism of protection may involve spasmolytic/vasodilatory agonist activity. The precise localization of beta3-adrenoceptors in the human gut is not known. AIM: To localize the beta3-adrenoceptor within the human gastrointestinal tract using the immunohistochemical technique. METHODS: Human beta3-adrenoceptors were immuno-localized in paraffin sections of human oesophagus (OS), stomach (ST), duodenum (DU), ileum (IL), sigmoid colon (SC), rectum (R) and gall-bladder (GB) using the rabbit polyclonal antibody anti-P12. Staining was graded , ++, + and 0. Immunostaining of SC was also done with pre-incubation of anti-P12 with P12 peptide. Western blotting of anti-P12 on human and murine IL and SC isolated membrane proteins was performed. RESULTS: All epithelia, vascular endothelial cells and ganglia scored 0. Smooth muscle of the vasculature, muscularis propria, muscularis mucosae and mucosa was graded, respectively, as follows; OS ( , , ,-), ST (++, , ++, ++), DU (++, , , +), IL (++, ++, ++, +), SC ( , ++, ++, ++), R (++, ++, +, +), GB ( , , -, 0). Pre-incubation of anti-P12 with P12 peptide almost abolished SC smooth muscle positivity. Western blot analysis using anti-P12 on human, but not murine, IL and SC membrane proteins revealed a single 5 5 kDa band, a size consistent with the predicted size of a partially glycosylated form of the human beta3-adrenoceptor. CONCLUSIONS: This immunohistochemical study has localized the beta3-adrenoceptor to vascular and nonvascular smooth muscle in the human gastrointestinal tract. These findings support a role for the beta3-adrenoceptor in the control of blood flow and motility in the human gastrointestinal tract.

Amino Acid Sequence↗
PubMed1998

Reversal and protection against indomethacin-induced blood stasis and mucosal damage in the rat jejunum by a beta3-adrenoceptor agonist.

BACKGROUND: In the rat, indomethacin causes jejunal villous shortening, microvascular distortion, and blood stasis prior to ulceration. The beta3-adrenoceptor agonist CL316,243 (CL) prevents both the early histological changes and ulceration. AIM: To test the hypothesis that the beta3-adrenoceptor agonist CL316,243 exerts its protective effect by prevention and/or reversal of blood flow changes in the rat jejunum exposed to indomethacin. METHODS: In anaesthetized rats, jejunal villous blood flow was measured in surface capillaries using fluorescence microscopy. Stasis of superficial capillary blood flow was induced by combined topical and i.v. indomethacin (100 microg/mL, 2.8 x 10(-4) M). To examine the effect of CL on blood stasis, CL was applied either i.v. (1 mg/kg) or luminally (100 microg/mL, 2.5 x 10(-5)M) at the onset of stasis. Prophylactic protection was assessed by giving i.v. CL simultaneously with indomethacin. Results were compared with controls which received luminal saline applied at blood stasis. The effect of i.v. CL (1 mg/kg) alone, or luminal CL (100 microg/mL) alone on basal villous blood flow was also examined. The small intestines were perfusion-fixed with 10% formol saline, and removed for histology, n = 5 for all groups. RESULTS: Luminal CL given at stasis reversed indomethacin-induced stasis within 10 min, whereas i.v. CL did not. Pretreatment with i.v. CL prevented the onset of stasis. Basal blood flow was raised slightly only by luminal CL. CONCLUSION: The beta-adrenoceptor agonist CL316,243 can protect against indomethacin-induced blood stasis in rat jejunal villi.

Adrenergic beta-Agonists↗
PubMed1998

Focal reduction of villous blood flow in early indomethacin enteropathy: a dynamic vascular study in the rat.

BACKGROUND: Oral indomethacin causes villous shortening, microvascular damage, and distortion, which might induce mucosal ischaemia and necrosis. AIMS: In order to determine the early events in indomethacin induced jejunal injury we examined the temporal relations between morphological damage and changes in villous blood flow following indomethacin. METHODS: In anaesthetised rats, mid jejunal villi were exteriorised in a chamber and observed by fluorescence microscopy. Blood flow in surface capillaries was calculated from velocities and diameters. Indomethacin was applied by both luminal and intravenous routes for 90 minutes, after which the animal was perfusion fixed and the villi were processed for histological examination. Control animals received intravenous or luminal bicarbonate (1.25%). RESULTS: Blood flow slowed in individual villi at 20 minutes, and progressed to complete stasis (in another group) by 45 minutes. Histological examination at 20 minutes revealed microvascular distortion, but no villous shortening; crypt depth:villous height ratios were 0.356 (0.02) in test and 0.386 (0.01) in surrounding villi (p > 0.05). At stasis, the villi under study showed epithelial clumping and were shortened: crypt depth:villous height ratios were 0.92 (0.2) in test and 0.42 (0.06) in surrounding villi (p < 0.02). Vehicle alone had no effect on either blood flow or histology. CONCLUSIONS: Focal slowing of villous blood flow and microvascular distortion precede villus shortening and epithelial disruption, and indicate that damage to surface microvasculature is an early event in indomethacin induced mucosal injury in this model.

Animals↗
PubMed1998

Absence of Escherichia coli, Listeria monocytogenes, and Klebsiella pneumoniae antigens within inflammatory bowel disease tissues.

BACKGROUND: Escherichia coli, listeria, and streptococcal antigens have been found in Crohn's disease tissues. Antibodies to Klebsiella pneumoniae have been found in patients with inflammatory bowel disease and ankylosing spondylitis. The presence of these bacterial antigens in Crohn's granulomas would be of aetiological interest, while their presence in ulcers alone would be more likely to indicate secondary infection. AIM: To investigate inflammatory bowel disease tissues for the presence of these bacteria. METHODS: Formalin fixed, paraffin processed sections from 53 patients (19 ulcerative colitis, 23 Crohn's disease; 11 normal tissues from cancer resections) were studied by immunohistochemistry. Control tissue consisted of normal human small bowel injected submucosally with either E coli, Listeria monocytogenes, Proteus mirabilis, or Klebsiella pneumoniae serotypes K2, 3, 17, 21, 26, 36, and 50, and colonic biopsies from a child with E coli 0114 infection. Tissues were stained by Gram-Twort, and with specific antibodies for E coli (Dako B357), L monocytogenes (Difco 2302-50), and K pneumoniae (Biogenesis 5580-5208) using an immunoperoxidase technique. RESULTS: Positive staining for E coli was observed on the luminal surface epithelium and in ulcers in 35% of Crohn's disease patients, 26% of ulcerative colitis patients, and no normal controls. Superficial staining for L monocytogenes was observed in one case of ulcerative colitis only. Staining for K pneumoniae was observed in one case of ulcerative colitis and one of Crohn's disease. No granulomas, giant cells, or germinal centres stained positively for any of the three bacterial antigens. CONCLUSIONS: These data do not support a primary role for E coli, L monocytogenes, and K pneumoniae in inflammatory bowel disease. The presence of E coli antigens in ulcers suggests secondary infection in these lesions.

Antigens, Bacterial↗
PubMed1997

Vascular anatomy defines sites of indomethacin induced jejunal ulceration along the mesenteric margin.

BACKGROUND: Indomethacin induces ulceration in the rat jejunum with sparing of the ileum. The ulcers localise between vasa recta along the mesenteric margin of the bowel, observations that have not been fully explained. AIM: To examine the relationship between the localisation of experimental ulcers and the vascular anatomy of the rat small intestine. METHODS: The normal vascular anatomy of the rat jejunum and ileum was studied and compared using arterial carbon ink perfusion. The anatomical localisation of early and advanced lesions induced by indomethacin was examined with particular reference to the vasculature. Mucosal injury induced by feeding vessel ligation for 24 hours or brief ischaemia-reperfusion injury was examined. The existence of anatomically sensitive sites to indomethacin was tested in a two dose study. RESULTS: In the rat jejunum, poorly vascularised sites along the mesenteric margin were highly susceptible to indomethacin induced injury, such sites being absent from the ileum. Villous contraction was a feature of both early indomethacin injury and ischaemia-reperfusion injury in the rat jejunum. Twenty four hour ligation of jejunal vasa brevia selectively induced ischaemic injury along the mesenteric margin. Two doses of indomethacin to rats did not induce greater injury than a single dose. CONCLUSIONS: Results support the hypothesis that the rat jejunum possesses vascularly compromised sites along the mesenteric margin that are susceptible to indomethacin induced injury. Indomethacin may cause ischaemia-reperfusion injury selectively at these sites.

Animals↗
PubMed1997

Ulceration of the ileum in Crohn's disease: correlation with vascular anatomy.

BACKGROUND: Ileal ulcers in Crohn's disease tend to lie along the same side of the bowel wall as the mesenteric attachment; the mesenteric and antimesenteric borders are supplied by short and long arteries, respectively. AIM: To examine the localisation of ileal Crohn's ulcers and to test the hypothesis that predilection of Crohn's ulcers for the ileal mesenteric margin is explained by the existence of end arteries that supply the mesenteric margin. METHODS: The localisation of ulcers in the bowel wall was examined in eight resection specimens of Crohn's disease of the terminal ileum. The vascular anatomy of normal terminal ileum (n = 8) and proximal jejunum (n = 8) postmortem specimens was studied; isolated long and short vessels were ligated before perfusion in four of these specimens. RESULTS: All eight specimens of Crohn's disease of the terminal ileum showed longitudinal ulceration along the mesenteric margin. In the postmortem study, the submucosal vascular plexus derived from ileal, but not jejunal short vessels, comprised end arteries with little or no communication with the submucosal plexus arising from long vessels. Prior ligation of ileal, but not jejunal, short vessels resulted in a filling defect of the submucosal plexus along the mesenteric margin in three of the four specimens. Ligation of ileal and jejunal long vessels did not affect carbon ink perfusion of the bowel wall. CONCLUSIONS: In the human terminal ileum, the short vessels supplying the mesenteric margin are end arteries, and their pathological occlusion might cause ischaemia of this region. These findings support a vascular hypothesis for Crohn's disease and may explain, in part, both the ileal and mesenteric distribution of Crohn's disease ulcers.

Aged↗
PubMed1997

Efficiency of human skeletal muscle in vivo: comparison of isometric, concentric, and eccentric muscle action.

The purpose of this study was to estimate the efficiency of ATP utilization for concentric, eccentric, and isometric muscle action in the human tibialis anterior and extensor digitorum longus in vivo. A dynamometer was used to quantitate muscle work, or tension, while simultaneous 31P-nuclear magnetic resonance data were collected to monitor ATP, phosphocreatine, inorganic phosphate, and pH. The relative efficiency of the actions was estimated in two ways: steady-state effects on high-energy phosphates and a direct comparison of ATP synthesis rates with work. In the steady state, the cytosolic free energy dropped to the lowest value with concentric activity, followed by eccentric and isometric action for comparative muscle tensions. Estimates of ATP synthesis rates revealed a mechanochemical efficiency [i.e., ATP production rate/work (both in J/s)] of 15.0 +/- 1.3% in concentric and 34.7 +/- 6.1% in eccentric activity. The estimated maximum ATP production rate was highest in concentric action, suggesting an activation of energy metabolism under these conditions. By using direct measures of metabolic strain and ATP turnover, these data demonstrate a decreasing metabolic efficiency in human muscle action from isometric, to eccentric, to concentric action.

Adenosine Diphosphate↗
PubMed1996

The beta 3-adrenoceptor agonist CL316243 prevents indomethacin-induced jejunal ulceration in the rat by reversing early villous shortening.

Jejunal villi undergo early histological shortening and vascular injury in indomethacin-induced ulcerative enteropathy in the rat. The protective effects of the beta 3-adrenoceptor agonist CL316243 on this rat model and the mechanism of action were examined using histological techniques. Groups of rats received oral indomethacin (15 mg/kg) and oral CL316243 (0, 0.01-10 mg/kg) 0.5 h beforehand. Jejunal ulceration was assessed 48 h after indomethacin. Other groups received CL316243 either 6 h before or 3 or 6 h after indomethacin. Plasma indomethacin and jejunal prostaglandin E2 levels were determined in groups of rats with and without prior CL316243. CL316243 was a potent dose-dependent inhibitor of jejunal ulceration (> 98 percent inhibition at doses > or = 0.1 mg/kg; ED50 = 0.025 mg/kg) but was not protective when given 6 h after indomethacin. CL316243, 1 mg/kg, reversed early villous shortening and vascular injury. CL316243 did not affect either indomethacin bioavailability or the inhibition of prostaglandin E2. To conclude, the beta 3-adrenoceptor agonist CL316243 is a potent inhibitor of indomethacin-induced jejunal ulceration and the mechanism of protection involves reversal of both villous shortening and vascular injury, which are usefully assessed by histomorphological techniques.

Adrenergic beta-Agonists↗
PubMed1996

Review article: beta 3-adrenoceptor agonists--future anti-inflammatory drugs for the gastrointestinal tract?

The beta 3-adrenoceptor is now a recognized sub-type of beta-adrenoceptor and is the principle adrenoceptor responsible for lipolysis in rat adipocytes. The receptor is also found in the gastrointestinal tract where beta 3-adrenoceptor agonists are both spasmolytic and potent inhibitors of experimental non-steroidal anti-inflammatory drug (NSAID)-induced gastric and small intestinal ulcers. There is evidence to suggest that the underlying mechanism of protection involves enhancement of mucosal blood flow, possibly as a result of relaxation of vascular and non-vascular smooth muscle. This review examines some possible therapeutic applications for beta 3-adrenoceptor agonists in ulcero-inflammatory disorders of the gastrointestinal tract where an altered blood flow state is a component of the underlying pathogenic process.

Adrenergic beta-Agonists↗
PubMed1996

Gastric mucosal contraction and vascular injury induced by indomethacin precede neutrophil infiltration in the rat.

BACKGROUND: In contrast with earlier reports that neutrophils play a primary part in non-steroidal anti-inflammatory drug (NSAID) injury to the stomach, recent evidence suggests only a secondary role for these cells. AIM: To examine whether early microscopic changes induced by indomethacin in the gastric corpus of fasted rats and the antrum of fasted-refed rats involve neutrophil infiltration. METHODS: Oral indomethacin 30 mg/kg or vehicle was given to six groups of fasted rats that were killed five, 15, and 30 minutes after dosing. Subcutaneous indomethacin 30 mg/kg was also given to six groups of fasted-refed rats that were killed one, two, and four hours later. Haematoxylin and eosin and reticulin stained sections were examined to identify mucosal architectural changes. The gastric mucosa was also examined immunohistochemically for actin, fibrin, and neutrophils. RESULTS: In both the corpus and antrum, indomethacin caused an early phase of mucosal injury that occurred prior to mucosal neutrophil infiltration. Within the superficial corpus mucosa, this phase preceded coagulative necrosis and included surface epithelial expulsion, mucosal contraction with capillary aggregation and distortion, intravascular vascular fibrin deposition, and capillary congestion. The antrum showed similar early changes except that full thickness mucosal coagulative necrosis was a predominant early finding. CONCLUSIONS: In two experimental models of NSAID gastric ulceration the mucosa undergoes early contraction, vascular fibrin deposition, and necrosis prior to neutrophil infiltration. These findings support a primary, neutrophil independent, ischaemic pathogenesis for NSAID gastric ulceration.

Animals↗
PubMed1995

Microdensitometric measures of cytoplasmic RNA and total protein in pyramidal neurons of the insular cortex and midfrontal gyrus in patients with Alzheimer's disease.

Scanning and integrating microdensitometry of azure B- and Coomassie brilliant blue G-stained tissue sections was used to measure the levels of RNA and protein, respectively, in pyramidal neurons of the insular cortex (INS) and midfrontal gyrus (MFG) in patients with Alzheimer's disease (AD) and age-matched, nondemented control subjects. AD was associated with a decreased neuronal RNA (by 7.4 per cent) and protein (by 28.7 per cent) content in INS. Although the neuronal RNA content was maintained at the control amounts in MFG, the average protein level was lower (14.7 per cent) in AD patients. These results demonstrate a disease-related impairment in metabolic function in two brain regions connected via discrete corticocortical pathways. Such findings support the hypothesis that a primary site of pathology occurs in AD, and specific neural deficits occur secondarily in certain connected brain regions.

Aged↗
PubMed1995

Management of spinal cord injured patients by indwelling suprapubic catheterization.

PURPOSE: We review the urological complications in spinal cord injury patients treated with suprapubic catheterization. MATERIALS AND METHODS: Suprapubic catheterization was used in 44 spinal cord injury patients. Followup ranged from 12 to 150 months (mean 58). The catheters were irrigated weekly and changed every 2 weeks. Patients were followed annually with urodynamic studies and ultrasound. RESULTS: No patient had renal deterioration, vesicoureteral reflux or bladder carcinoma. The incidences of incontinence, urinary tract infections and calculi were acceptable. CONCLUSIONS: Suprapubic catheterization is an effective and safe alternative form of bladder management in select patients with spinal cord injury.

Adolescent↗