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Biomedical subjects

M R Thompson

Publications and source records attributed to M R Thompson.

At least 19 recordsLinked to original sources
PubMed2003

Evidence of the effect of 'specialization' on the management, surgical outcome and survival from colorectal cancer in Wessex.

BACKGROUND: A prospective audit of the management of colorectal cancer was established to investigate factors associated with variation in survival observed within the former Wessex region (population three million). METHODS: Some 5173 patients (4562 surgically treated) with colorectal cancer diagnosed between 1991 and 1994 were followed for 5 years. Details of referral, diagnosis, surgical treatment, postoperative complications and outcomes were collected. The association between surgical outcomes and survival and both case volume and specialization (defined to include membership of the Association of Coloproctology of Great Britain and Ireland) was explored, accounting for variables with prognostic significance. RESULTS: There was a statistically significant association between high-volume operators (more than 50 operations per year) and specialization. The greatest benefit was observed with respect to specialists versus non-specialists, in terms of a lower postoperative mortality rate (odds ratio 0.67 (95 per cent confidence interval (c.i. 0.53 to 0.84)), lower anastomotic leak rates (odds ratio 0.46 (c.i. 0.31 to 0.66)), higher local recurrence-free survival (hazard ratio 0.56 (0.44 to 0.71)) and better long-term survival (hazard ratio 0.76 (c.i. 0.71 to 0.83)). CONCLUSION: There is a stronger association between surgical specialization in coloproctology and beneficial outcome than with high-volume caseloads. This is not entirely accounted for by case-mix or patient population, and is seen following colonic and rectal surgery and among patients with advanced disease.

Adolescent↗
PubMed2002

Faecal contamination and enterotoxigenic Escherichia coli in street-vended chili sauces in Mexico and its public health relevance.

The street-vended food industry provides employment and cheap ready-to-eat meals to a large proportion of the population in developing countries like Mexico, yet little is known about its role in the transmission of food borne diseases (FBD). Because of its wide consumption, street-vended chili sauces in Mexico are potential vehicles of FBD. An observational study was performed in Mexico City collecting 43 street-vended chili sauces. These sauces were prepared under poor hygienic conditions of handling and selling. Consumers add 4-8 ml of chili sauce per taco, ingest 2-5 tacos per meal and on average, 50 consumers frequent a stall per day. Seventeen (40%) samples were faecally contaminated and 2(5%) sauces harboured sufficient enterotoxigenic Escherichia coli to cause disease. Weestimate that the consumption of only one of these chili sauces could result in ETEC disease inat least 21,000 consumers per year, making them important potential vehicles of FBD.

Escherichia coli↗
PubMed2000

Evaluation of Delorme's procedure as a treatment for full-thickness rectal prolapse.

BACKGROUND: Delorme's procedure is a well tolerated perineal operation for full-thickness rectal prolapse. However, prolapse recurrence is common and reported recurrence rates vary widely. This study attempted to standardize outcome assessment for recurrence following primary and subsequent Delorme's operations. Patient and operative factors were analysed to identify any that might improve patient selection. METHODS: Some 101 primary and 17 secondary Delorme's procedures were carried out on 113 consecutive patients presenting with rectal prolapse, who were followed for a minimum of 12 months, unless death or recurrent prolapse intervened. The rate of prolapse recurrence was calculated using the Kaplan-Meier method of analysis. Patient age, sex, grade of incontinence, presence of diverticular disease, length of mucosal resection and position in the operative series were analysed to identify factors affecting recurrence. RESULTS: The predicted recurrence-free period for 50 per cent of patients undergoing primary and secondary Delorme's procedures was 91 (95 per cent confidence interval 77-105) and 27 (15-39) months respectively. None of the patient or operative factors analysed was related to recurrent prolapse. CONCLUSION: Delorme's procedure is a simple operation with satisfactory functional results which can be considered in all patients of all ages. However, high recurrence rates for primary and repeat operations should be explained to patients when planning their surgical management.

Adult↗
PubMed2000

Bascom's operation in the day-surgical management of symptomatic pilonidal sinus.

BACKGROUND: Many treatments for symptomatic pilonidal sinus disease have been described. Ambulatory treatment with minimal morbidity and a rapid return to normal activity is desirable. Bascom's operation fulfils these requirements. This paper describes the operative technique and results of treatment. METHODS: Some 218 patients of mean age 27 years were treated as day cases. The mean duration of symptoms was 2.4 years. Sixty-eight per cent of patients had complex disease with more than two midline pits and/or a lateral discharging sinus. One hundred and eighty-three patients (84 per cent) were operated on under local anaesthesia. RESULTS: Ninety-five per cent of patients have been followed up for a mean of 12.1 (range 1-60) months. All except one midline wound healed. Lateral wounds healed after a mean of 4.0 (range 1-15) weeks. Postoperative complications were few, including bleeding in 4 per cent and abscess formation treated by reopening the lateral incision in 6 per cent. Twenty-one patients (10 per cent) have had recurrence and have needed reoperation. CONCLUSION: Bascom's operation is simple and results in considerable financial savings with minimal social disruption and an early return to work. Recurrent disease is no more frequent than after other treatments.

Adolescent↗
PubMed2000

Structural and functional features of modified heat-stable toxins produced by enteropathogenic Klebsiella cells.

Heat-stable enterotoxins (STs) are 18- or 19-amino acid peptides (STa or ST1) produced by enteropathogenic bacteria with small differences in their amino acid sequence and a highly conserved carboxy terminus. All STs contain a core of three disulfide bridges whose integrity is believed to be necessary for full biologic activity. We previously reported that strains of Klebsiella pneumoniae transformed by the plasmid pSLM004 produce a modified toxin not recognized by MAb raised against genuine Escherichia coli ST. Investigation of the chemical structure of the modified toxins revealed that three new toxins were present. These were purified to homogeneity by a series of sequential chromatography on reverse-phase columns using guanylate cyclase to monitor the enterotoxic activity during purification procedures. The sequence of the modified toxins was obtained by a combination of Edman degradation and mass spectrometry, showing that they are proteolytically processed forms of E. coli ST1b. In particular, toxin A-2 lacks the cysteine at position 18 and then is not able to form the disulfide bridge cysteine-10-cysteine-18. All three toxins showed the ability to stimulate guanylate cyclase and to elicit chloride secretion in Caco-2 cell monolayers mounted in Ussing chambers. Toxin A-1 and toxin B demonstrated greatly reduced immunoreactivity whereas toxin A-2 was not recognized at all in the ELISA. It is likely that the three modified toxins were generated by Klebsiella specific proteolytic processing of the original pretoxin. These results have important implications for the diagnosis and prevention of heat-stable toxin-induced diarrhea.

Antibodies, Bacterial↗
PubMed1999

Increased-contrast, high-spatial-resolution, diffusion-weighted, spin-echo, echo-planar imaging.

An insertable head gradient coil with a maximum gradient amplitude of 45 mT/m and a rise time of 150 musec along all three major axes was used to collect high-spatial-resolution, single-shot, spin-echo, echo-planar, diffusion-weighted magnetic resonance images with b values ranging from 0 to 2,200 sec/mm2. Improvements in spatial resolution allowed better visualization of large white matter tracts and their relation to adjacent anatomic structures. Excellent contrast and anatomic detail were revealed for most structures in the brain when a sufficient number of acquisitions were collected.

Adult↗
PubMed1995

Physiological changes after Delorme's procedure for full-thickness rectal prolapse.

Anal sphincter pressures, rectal compliance and sensation in 19 women of mean age 77 (range 57-94) years were studied before and after Delorme's procedure for full-thickness rectal prolapse. No patient had significant problems with defaecation after operation. There were no significant changes in anal sphincter pressures but the volume of first rectal sensation decreased from a median of 140 ml before surgery to 65 ml after the procedure (P = 0.01) and the maximum tolerated rectal volume declined from a median of 249 ml to 120 ml (P = 0.001). Rectal compliance was reduced from a median of 142.9 ml/kPa to 12.2 ml/kPa (P = 0.002). Improved rectal sensation and lowered compliance are associated with a reduced incidence of defaecatory problems after Delorme's procedure.

Aged↗
PubMed1993

Receptors for Escherichia coli heat stable enterotoxin in human intestine and in a human intestinal cell line (Caco-2).

Escherichia coli heat stable enterotoxin (STa) and the newly identified endogenous ligand guanylin bind to an intestinal receptor and activate membrane bound guanylate cyclase. We compared STa binding and affinity crosslinking of STa receptors in human small intestine to those in the Caco-2 human colon carcinoma cell line. STa had similar kinetics of binding in human intestinal and Caco-2 brush border membranes. In both human intestine and Caco-2 brush border membranes, multiple specifically radiolabeled bands, including a 140-165 kDa band, were identified by affinity crosslinking. However, in human intestine the most prominent autoradiographic species was a 60 kDa band. A 60 kDa protein was also specifically immunoprecipitated from solubilized human brush border membranes using antisera raised against a cloned STa receptor fusion protein. Our observations of multiple crosslinked proteins in human intestine and Caco-2 cells could be explained by the existence of several members of a family of STa receptors and/or the existence of smaller STa binding proteins generated by the protease cleavage of a larger complete STa receptor.

Bacterial Toxins↗
PubMed1992

The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein binds and internalizes Pseudomonas exotoxin A.

The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2 MR/LRP) is a large cell-surface glycoprotein consisting of a 515-kDa and an 85-kDa polypeptide; this receptor is thought to be responsible for the binding and endocytosis of activated alpha 2-macroglobulin and apoE-enriched beta-very low density lipoprotein. A similar high molecular weight glycoprotein has been identified as a potential receptor for Pseudomonas exotoxin A (PE). We demonstrate that the alpha 2 MR/LRP and the PE-binding glycoprotein have a similar mobility upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis and are immunologically indistinguishable. Furthermore, affinity-purified alpha 2 MR/LRP binds specifically to PE but not to a mutant toxin defective in its ability to bind cells. The 39-kDa receptor-associated protein, which blocks binding of ligands to alpha 2 MR/LRP, also prevents binding and subsequent toxicity of PE for mouse fibroblasts. The concentration of receptor-associated protein that was required to reduce binding and toxicity to 50% was approximately 14 nM, a value virtually identical to the KD measured for the interaction of receptor-associated protein with the purified receptor. Overall, the studies strongly suggest that the alpha 2 MR/LRP is responsible for internalizing PE.

ADP Ribose Transferases↗
PubMed1991

Isolation and characterization of Pseudomonas aeruginosa exotoxin A binding glycoprotein from mouse LM cells.

A Pseudomonas aeruginosa exotoxin A (PE) binding glycoprotein was affinity purified from toxin sensitive mouse LM cells. The binding protein was solubilized with Triton X-100 or Nonidet P-40 and purified on a PE-Sepharose affinity column. Polyacrylamide gel electrophoresis yielded a single band with an estimated molecular mass of greater than 300,000 Da. N-Linked carbohydrate was present, accounting for approximately 10% of the total mass of the molecule. The purified protein specifically bound PE. Incubation of purified protein specifically bound PE. Incubation of purified PE binding protein with toxin reduced toxicity to LM cells. We speculate on the role of this toxin binding glycoprotein in the intoxication process.

ADP Ribose Transferases↗
PubMed1991

Mouse liver contains a Pseudomonas aeruginosa exotoxin A-binding protein.

The opportunistic pathogen Pseudomonas aeruginosa produces several potential virulence factors, including the ADP-ribosylating toxin, exotoxin A (PE). Studies using a burned mouse model have shown that PE consistently inhibits protein synthesis and depletes elongation factor 2 in mouse liver and variably in other organs. One reason for toxin sensitivity could be the presence of a PE receptor on the surface of cells. Therefore we examined detergent extracts of mouse tissues for the presence of toxin-binding proteins. Proteins which specifically bind PE were present in extracts from liver, kidney, lung, spleen, and heart. Because liver appears to be a prominent target for the toxin in a burned animal, we choose to isolate the PE-binding protein from mouse liver and compare this protein to the recently characterized toxin-binding protein from toxin-sensitive mouse LM fibroblasts. The toxin-binding proteins from both sources have a molecular mass of approximately 350 kDa, share similar protease digestion profiles, and are glycosylated. However the glycosylation patterns for the two species are quite different. Both glycoproteins bind toxin with high avidity. The toxin-binding moiety is located, at least in part, on the plasma membrane and thus could represent the receptor involved in internalization of toxin molecules responsible for cell death.

ADP Ribose Transferases↗
PubMed1990

Preparation of stable 125I cyclic GMP tyrosine methyl ester suitable for 3',5' cyclic GMP radioimmunoassay by HPLC.

Determination of the concentration of cyclic guanosine monophosphate (cGMP) by radioimmunoassay (RIA) depends upon the availability of suitable radiolabeled tracers and antibody to detect the product. Reverse phase chromatographic techniques can easily separate the reaction products of chloramine-T iodination of succinyl cGMP tyrosine methyl ester. The binding characteristics of the iodination reaction products to anti-cGMP antibody have been determined. Purified succinyl cyclic nucleotide 125I-tyrosine methyl ester binds to cGMP antisera identically as commercially available tracer. The tracer is stable for greater than three months.

Chromatography, High Pressure Liquid↗
PubMed1990

Mutants of staphylococcal toxic shock syndrome toxin 1: mitogenicity and recognition by a neutralizing monoclonal antibody.

Toxic shock syndrome toxin 1 (TSST-1), a 22-kilodalton protein made by strains of Staphylococcus aureus harboring the chromosomal toxin gene, may elicit toxic shock syndrome in humans. In vitro, TSST-1 induces T cells to proliferate and macrophages to secrete interleukin-1. To conduct a structure-function analysis, point mutations on the TSST-1 gene were generated by site-directed mutagenesis to identify amino acids critical for activity of the toxin. Specific tyrosine and histidine residues were replaced by alanines. Wild-type and mutant TSST-1 gene constructs were expressed in Escherichia coli, and the products were tested for their mitogenic potential and reactivity with a TSST-1 neutralizing monoclonal antibody (MAb 8-5-7). Four of the mutants were similar to the wild type; i.e., the mutant toxins stimulated murine T cells and reacted with MAb 8-5-7 equally as well as the wild type. Two mutants exhibited a decrease in mitogenic activity, but one of these retained the capacity to bind with MAb 8-5-7 while the other was no longer recognized by the same antibody. One double mutant demonstrated minimal mitogenic activity and did not react in enzyme-linked immunosorbent and immunoblot assays with MAb 8-5-7. The data show that specific residues near the carboxy terminus of TSST-1 are essential for mitogenic activity and in forming the epitope recognized by neutralizing MAb 8-5-7.

Animals↗