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Biomedical subjects

D Youngs

Publications and source records attributed to D Youngs.

At least 19 recordsLinked to original sources
PubMed1995

Cytokine production in pouchitis is similar to that in ulcerative colitis.

PURPOSE: Controversy exists as to whether pouchitis represents a reactivation of the immunologic mechanisms that lead to ulcerative colitis (UC). The aims of this study were to determine local levels of the cytokines: interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF alpha) in the mucosa of patients with "asymptomatic" ileoanal pouch (n = 25), pouchitis (n = 9), active UC (n = 20), normal ileum (n = 15), proctitis (n = 10), and normal colon (n = 15). METHODS: Lamina propria mononuclear cells were isolated from mucosal biopsies by enzymatic dispersion and cultured for 48 hours. Proinflammatory cytokine levels were measured in the supernatants by enzyme-linked immunosorbent assay. RESULTS: IL-1 beta, IL-6, IL-8, and TNF alpha secretions were significantly greater in pouchitis and active UC than in the noninflamed ileoanal pouch and normal controls (P < 0.001). There was significant correlation (r = 0.63, P < 0.05) between levels of cytokines expressed in pouchitis and active UC. CONCLUSIONS: Increased cytokine expression occurs in both active UC and pouchitis and to a lesser extent in the long-standing ileoanal pouch.

Adolescent↗
PubMed1994

Interleukin 6 is a prognostic indicator of outcome in severe intra-abdominal sepsis.

Levels of plasma cytokines and circulating endotoxin were assessed in 41 patients with severe intra-abdominal sepsis. Comparison was made with the Acute Physiology And Chronic Health Evaluation (APACHE) II scoring system. Blood samples were taken within 24 h of onset of the sepsis syndrome and at serial times thereafter. Increased levels of interleukin (IL) 6 (range 50-25,500 pg/ml) were detectable in all patients with sepsis. Eighteen of the 19 deaths were attributable to sepsis and higher levels of IL-6 at the onset of the sepsis syndrome correlated with a poor outcome. The sensitivity of IL-6 concentration in predicting mortality was 86.4 per cent with a specificity of 78.9 per cent and an overall correct classification rate of 82.9 per cent. IL-6 level was a better predictor than APACHE II score (sensitivity 72.7 per cent, specificity 57.9 per cent, correct classification rate 65.9 per cent). Levels of tumour necrosis factor alpha, IL-1 beta and endotoxin did not correlate with mortality rate. Plasma IL-6 concentrations may help in planning future strategies to decrease the mortality rate associated with sepsis.

Abdomen↗
PubMed1994

Faecal diversion for Crohn's colitis: a model to study the role of the faecal stream in the inflammatory process.

The high incidence of clinical remission after faecal diversion for Crohn's colitis suggests the faecal stream may play a part in the inflammatory mechanism. The effect of faecal diversion (n = 22) and restoration of intestinal continuity (n = 10) was assessed in patients with Crohn's colitis and compared with controls. Faecal diversion produced significant improvement in the disease activity index mean (SEM) (before 176 (9); after 114 (9), p < 0.01) and serum albumin concentrations (before 33 (3.0); after 38 (3.0), p < 0.05) in all patients with Crohn's colitis. The crypt cell production rate (CCPR) was maintained after faecal diversion for Crohn's colitis but fell in the control group (before = 3.6 (0.8)), at two (1.4 (0.4), p < 0.02), and six weeks (1.6 (0.4), p < 0.05). Mucosal glucosamine synthetase activity, reflecting glycoprotein synthesis, was significantly lower in patients with Crohn's colitis (analysis of variance p < 0.05) after diversion but was maintained in the control group. Restoration of intestinal continuity failed to produce reciprocal changes. The sustained cellular proliferation and fall in glycoprotein synthesis in Crohn's colitis after faecal diversion may represent the end of an exaggerated protective response and regenerative hyperplasia after exclusion of the faecal stream. This study suggests the faecal stream may participate in the inflammatory process in Crohn's colitis. The underlying mechanism is unknown.

C-Reactive Protein↗
PubMed1993

Mucosal morphology, cell proliferation and faecal bacteriology in acute pouchitis.

A study was performed to investigate whether acute reservoir ileitis (pouchitis) is associated with specific changes in mucosal morphology, crypt cell kinetics and faecal bacteriology in the ileal pouch. Forty-six patients were studied (ileal reservoir, 36; end ileostomy, ten) using clinical grading, sigmoidoscopy and biopsy; 24 patients with a reservoir were restudied after therapy for 1 month with metronidazole 400 mg three times daily. An index of villus atrophy and crypt cell production rate (CCPR) were determined in all biopsy material. Faecal bacteriology was assessed in 12 patients with a pouch before and after metronidazole therapy. The mucosa of patients with pouchitis was associated with a lower villus atrophy index (P = 0.052), a higher CCPR (P = 0.03) and a higher grade of acute inflammation than that in those without pouchitis. There was no difference in faecal bacterial counts between patients with and without pouchitis. A low atrophy index correlated with a high CCPR (P < 0.001), worse functional score (P < 0.001) and more severe pouch mucosal acute inflammation (P < 0.001), but not with faecal bacteriology. Following metronidazole therapy there was resolution of acute pouch inflammation, increased villus atrophy index (P = 0.049), decreased CCPR (P = 0.049) but no differences in faecal bacterial counts apart from Bacteroides species. These data show that metronidazole therapy does not specifically alter the growth of common faecal bacteria in patients with pouchitis, apart from Bacteroides species. However, metronidazole causes resolution of the typical changes in pouch mucosal morphology and crypt cell kinetics associated with pouchitis.

Adult↗
PubMed1992

Influence of dietary calcium supplements on ileoanal pouch function and cytokinetics.

A double-blind cross-over study was undertaken in 16 patients after panproctocolectomy and ileoanal pouch reconstruction to compare supplementary calcium (1.5 g/day) with placebo over 2 months with a 2-week washout period. Stool frequency was recorded and the effects on pouch mucosal crypt cellular proliferation were determined using an in vitro stathmokinetic technique which measures the crypt cell production rate (CCPR) and an immunohistochemical method using the Ki67 monoclonal antibody for proliferating nuclei. The median (interquartile range) diurnal stool frequency was reduced by calcium (4 (3-5) per day) compared with values obtained before treatment (7 (5-10) per day, P less than 0.002) and with placebo (7 (6-9) per day, P = 0.002). Similarly, calcium reduced nocturnal stool frequency (1 (0-1) per night) compared with pretreatment and placebo (both 2 (1-3) per night, P less than 0.05) values. Calcium reduced the mean(s.e.m.) CCPR to 1.88(0.41) cells per crypt per hour compared with pretreatment (3.63(0.53), P = 0.01) and placebo (3.24(0.43), P = 0.002) values. Median (interquartile range) Ki67 activity was also reduced by calcium (13.2 (9.7-16.7) per cent), compared with values obtained before treatment (27.3 (14.3-30.2) per cent, P = 0.001) and with placebo (26.0 (17.2-32.0) per cent, P = 0.001). Stool frequency was significantly correlated with the CCPR (diurnal: r = 0.37; nocturnal: r = 0.31, both P less than 0.05). Nine patients used antidiarrhoeal medication while receiving placebo compared with four patients receiving calcium (P = 0.032). This study has shown that supplementary oral calcium significantly reduced stool frequency in patients with pouches, a reduction that was associated with reduced cell proliferation. The mechanisms for this effect are not known.

Administration, Oral↗
PubMed1992

Reduction of mucosal crypt cell proliferation in patients with colorectal adenomatous polyps by dietary calcium supplementation.

The crypt cell production rate was measured in 14 patients with adenomatous colorectal polyps, 17 patients with colorectal cancer and 12 control subjects. The median (interquartile range) rate (cells per crypt per hour) was found to be significantly higher (P less than 0.001) in the polyp (2.45 (1.94-3.20)) and cancer (3.01 (2.35-3.68)) groups compared with controls (1.25 (0.70-1.85)). A double-blind cross-over study was performed in patients with adenomatous polyps consisting of 2 months' treatment, 2 weeks' washout, followed by 2 months' treatment with dietary calcium supplementation (1.25 g day-1) versus placebo. A significant reduction in the crypt cell production rate occurred with calcium treatment compared with the placebo (1.25 (0.6-2.25) versus 2.15 (1.58-3.08) cells per crypt per hour, P = 0.035). This study demonstrates a significant reduction in mucosal cell proliferation by dietary calcium supplementation in patients with adenomatous polyps. Such treatment may be worthy of further investigation in patients at high risk of developing colorectal polyps.

Aged↗
PubMed1992

Crypt cell production rates at various sites around the colon in Wistar rats and humans.

The crypt cell production rate (CCPR) is considered the most robust estimate of cell turnover. The CCPR was determined at various sites around the colon in the Wistar rat (using an in vivo technique) and in six healthy humans (using in vitro organ culture). In both the rat and human colon, the CCPR increased proximally from the rectum to the caecum. The caecum had a significantly higher cell turnover than any other site in the colon (p < 0.05 in the rat, p < 0.01 in humans, Student's t test). These findings are of interest when considering cellular proliferation studies in both inflammatory bowel disease and colorectal cancer, and draw attention to the importance of choosing a constant reference site for comparative studies. This is the first time the CCPR had been measured along the length of the human colon.

Adult↗
PubMed1990

Short-term chemoprophylaxis with ceftizoxime vs. five-day aminoglycoside with metronidazole in 'contaminated' lower gastrointestinal surgery.

In a prospective, open, randomized controlled trial, 173 patients requiring surgery for potentially "contaminated" lower gastrointestinal surgery were allocated to receive either two doses of ceftizoxime (2 gm) with one dose of metronidazole (1.5 gm) or gentamicin 3 mg/kg/day for five days with one dose of metronidazole (1.5 gm). Eighty-nine patients received ceftizoxime and 84 patients received gentamicin. The groups were comparable with respect to diagnosis, procedure, type of anastomosis, and wound closure. The incidence of withdrawal due to failure to respond to the study drug (11.5 percent) was equivalent in the two groups. There was no difference in the overall incidence of postsurgical infection between the ceftizoxime and metronidazole group (22.2 percent) and the gentamicin and metronidazole group (25.7 percent). The incidence of wound infection (ceftizoxime and metronidazole, 6.9 percent; gentamicin and metronidazole, 10 percent) and deep sepsis (ceftizoxime and metronidazole, 15.3 percent; gentamicin and metronidazole, 15.7 percent) was similar.

Aminoglycosides↗
PubMed1988

Gastric juice factors after Roux-Y reconstruction compared with Billroth II partial gastrectomy.

Gastric juice was studied in five patients after Billroth II partial gastrectomy, in six patients after Roux-Y reconstruction, and in eight healthy control subjects. Juice was obtained over a 24 hour period by hourly nasogastric aspiration prior to measurement of pH, total and stable N nitrosocompounds, nitrites, bile acids (total and free), and bacterial count. Large variations in almost all compounds were seen during the 24 hour period in individual patients, and in addition, there were large variations between patients within the clinical groups. The gastric juice pH concentration was higher in the Billroth II group, as was the bacterial flora count (median 3 X 10(6) organisms/ml). Although Roux-Y bile diversion reduced the exposure to bile acids, it did not prevent it, and bacterial proliferation was increased (1 X 10(7) organisms/ml). No significant differences or sizeable trends were seen in N nitrosocompounds or nitrite concentrations.

Anastomosis, Roux-en-Y↗
PubMed1986

Incidence of bile reflux in gastric ulcer and after partial gastrectomy.

Duodenogastric bile reflux (DGBR) is reported to be increased in patients with gastric ulcer (GU) and following Billroth I partial gastrectomy (BIPG). pH, total bacterial counts, and total and free bile acids were measured in gastric juice aspirated hourly for 24 h in 6 patients with GU, 7 patients with a BIPG performed for GU and in 8 healthy normal controls. Intragastric pH was significantly higher in the BIPG group during the day (P less than 0.001) and at night (P less than 0.001) compared with normals and the GU group. There were no differences between GUs and normal patients. Bile acid concentrations in the gastric juice were not significantly different between GU and control groups over the 24 h. Median and range values were 0.14 (0.06-0.52) mmol l-1 in GU patients and 0.14 (0.05-0.67) mmol l-1 in the normals. However total bile acid concentrations were significantly greater in the BIPG group (0.23, 0.04-0.84) compared with GU or controls. (P = 0.04, P = 0.02). Our data do not support the role of DGBR in the pathogenesis of GU, but deoxycholic acid was detected in significantly greater amounts in BIPG subjects than controls (chi 2 = 12.94, P less than 0.001) or GU subjects (none detected) and may be important in the pathogenesis of gastric stump cancer.

Adult↗
PubMed1985

The effect of a single intravenous dose of cefotaxime on the faecal flora.

Cefotaxime had an immediate effect on the faecal flora, mainly involving a loss of gram-positive organisms, but also reducing the number of Escherichia coli, Bacteroides spp. and Clostridium spp. There was little effect on the total bacterial counts because of compensatory increases in other species. These changes appear to initiate a period of instability in the composition of the faecal flora lasting for at least 14 days after the administration of cefotaxime. Other third-generation cephalosporins showed a similar prolonged disturbance to the stability of the faecal flora, but there were minor differences from cefotaxime in the bacterial species initially affected.

Bacteria↗
PubMed1985

Antibiotic therapy for treatment in relapse of intestinal Crohn's disease. A prospective randomized study.

We have undertaken a prospective randomized trial of one month's antimicrobial therapy for patients with symptomatic relapse of Crohn's disease. Criteria for entry included two major symptoms: fever, abdominal pain, diarrhea, weight loss, abdominal mass or complications (excluding perianal disease); and two hematologic abnormalities: hemoglobin, ESR, albumin, C reactive protein, iron, or total iron binding capacity. Patients were monitored for the aforementioned clinical and hematologic (hemoglobin, albumin, CRP) parameters over six weeks and for changes in fecal flora. Randomization was to four groups: metronidazole alone (M), cotrimoxazole alone (C), metronidazole and cotrimoxazole (C plus M), or double placebo (P). Seventy-two patients entered the study (18 = M, 16 = C, 21 = C plus M, 17 = P). After two weeks, improvement was reported as follows: M = 67 percent, C = 17 percent, C plus M = 71 percent, P = 35 percent. In the metronidazole group, two patients required surgery and one had troublesome side effects. In the cotrimoxazole group, two had side effects. In the combined group (C plus M), four had troublesome side effects and two of the placebo group (P) required operation. By four weeks, there was no difference in response among the groups: (M = 44 percent, C = 62 percent, C plus M = 57 percent, P = 41 percent). Antimicrobials had no effect on fecal flora or hematologic parameters. These results indicate that antimicrobials have little therapeutic potential for relapse of intestinal Crohn's disease.

Adult↗
PubMed1984

Intragastric N-nitrosation is unlikely to be responsible for gastric carcinoma developing after operations for duodenal ulcer.

Three groups of patients studied after operations which had cured their duodenal ulcer were compared with a control group (no operation, n = 8). The surgical procedures included: proximal gastric vagotomy (n = 7), truncal vagotomy and pyloroplasty (n = 7), truncal vagotomy and antrectomy (n = 8). Samples of gastric juice were aspirated half hourly or hourly over 24 hours for measurement of pH, counts of all identified bacteria, nitrite and total N-nitrosocompounds. Although the pH over 24 hours was significantly higher after proximal gastric vagotomy (p less than 0.05) and truncal vagotomy and antrectomy (p less than 0.001) than controls, there was no difference between truncal vagotomy and pyloroplasty and controls. Counts of nitrate reducing bacteria over 24 hours were also significantly higher after truncal vagotomy and antrectomy than controls (p less than 0.1) but no differences were observed between the other groups. Only after truncal vagotomy and antrectomy was nitrite over 24 hours significantly increased compared with controls (p less than 0.01). Despite these higher values after truncal vagotomy and antrectomy, there was no significant difference in total N-nitrosocompounds between any of the four groups. Whereas bacterial counts and nitrite increased with pH, no correlation was found between total N-nitrosocompounds and pH. These results provide no evidence that exposure to total N-nitrosocompounds is increased after operations for duodenal ulcer.

Bacteria↗
PubMed1984

Mutagenicity in gastric juice.

Mutagenicity has been measured in the gastric juice of 228 patients using the Ames bacteriological test system; while mutagenicity in control and duodenal ulcer patients did not differ from saline controls, mutagenicity was significantly increased compared with controls in patients suffering gastric ulcer (p less than 0.002), carcinoma (p less than 0.002), and in patients after gastric resection (p less than 0.01). A transient rise in mutagenicity was seen following H2 antagonist ingestion (p less than 0.002). Increased levels of mutagenicity were found to correlate closely with gastric juice pH and bacterial count. Histidine concentrations in gastric juice did not explain the mutagenicity results.

Duodenal Ulcer↗
PubMed1982

Randomized controlled trial of colestipol in antibiotic-associated colitis.

Thirty-eight patients with severe antibiotic-associated postoperative diarrhoea were entered into a randomized controlled trial to compare colestipol (an ion exchange resin) in 17 patients with placebo (sherbet) in 21 patients. Clostridium difficile or its toxin was present before treatment in 12 of the colestipol group, compared with only 5 in the placebo group. Because of the low incidence of Cl. difficile or its toxin, the placebo group data from 22 patients receiving placebo in a previous trial (9 of whom had Cl. difficile or toxin) were included for comparison. Neither colestipol nor placebo had any influence on the faecal excretion of Cl. difficile or its toxin. Colestipol was clinically no better than placebo. In view of the persistent faecal excretion of Cl. difficile toxin, ion exchange resins cannot be recommended for the treatment of antibiotic-associated colitis.

Anti-Bacterial Agents↗
PubMed1982

Clostridium difficile toxin in acute diarrhoea complicating inflammatory bowel disease.

The incidence of Clostridium difficile cytotoxin has been studied in 69 consecutive patients with inflammatory bowel disease complicated by severe diarrhoea or ileostomy flux during 74 admissions to hospital. The cytotoxin was identified in only four patients, all of whom had received antimicrobials. Clostridium difficle, but not cytotoxin, was identified in 10 of 43 admissions. This followed antimicrobial prophylaxis to cover a recent operation in two patients, and five were on long-term sulphasalazine. Only three patients with Clostridium difficile had not received an antimicrobial within one month of the study. Isolation of Clostridium difficile alone is of doubtful pathological significance, as it spontaneously disappeared without treatment in all patients.

Adult↗
PubMed1981

A controlled trial to compare systemic and intra-incisional cefuroxime prophylaxis in high risk gastric surgery.

A prospective randomized controlled trial has compared single dose systemic cefuroxime (n = 27) or intra-incisional cefuroxime (n = 26) with a control group (n = 28) in 81 patients undergoing gastric resection, revision gastric surgery or operation for gastro-oesophageal malignancy. In the controls the incidence of sepsis was: 35 per cent wound infection, 29 per cent abscess, 21 per cent septicaemia. After intra-incisional cefuroxime the incidence was: 4 per cent wound sepsis, 19 per cent abscess and 4 per cent septicaemia. After systemic cefuroxime only 2 patients developed wound sepsis (7 per cent) with no cases of abscess or septicaemia. Excluded from this high risk group were 36 patients who had a vagotomy with or without drainage during the trial where antibiotics were not given, 4 of whom developed wound sepsis only (11 per cent). There was a poor correlation between the individual species isolated from the gastric aspirate and the organisms responsible for postoperative infection in the controls, but there was a good correlation between fasting gastric pH and the risk of sepsis in the controls.

Bacteria↗