Biomedical subjects

R I Russell

Publications and source records attributed to R I Russell.

At least 37 records · Page 2Linked to original sources

PubMed1997

Helicobacter pylori eradication may reduce the risk of gastroduodenal lesions in chronic NSAID users.

Helicobacter pylori and non-steroidal anti-inflammatory drugs are two of the most common causes of peptic ulceration. The aim of this review is to assess the possible inter-relationships between Helicobacter pylori and non-steroidal anti-inflammatory drugs in the pathogenesis of gastric and duodenal erosions and ulcers, with the aim of assessing if the presence of Helicobacter pylori is likely to increase the likelihood of non-steroidal anti-inflammatory drug-related gastroduodenal symptoms and lesions, and if eradication of Helicobacter pylori may reduce or prevent non-steroidal anti-inflammatory drug lesions. There appears to be more likelihood of dyspeptic symptoms in patients on long-term non-steroidal anti-inflammatory drugs when Helicobacter pylori is present. The balance of evidence also suggests that peptic ulcers and erosions in patients on long-term non-steroidal anti-inflammatory drugs may be more likely to occur in patients who are Helicobacter pylori positive compared to those who are Helicobacter pylori negative. Although Helicobacter pylori and non-steroidal anti-inflammatory drugs both increase the risk of peptic ulcer bleeding, the risk does not appear to be additive. There is increasing evidence from prospective studies that eradication of Helicobacter pylori may reduce the incidence of ulcers in patients on non-steroidal anti-inflammatory drugs. More prospective long-term studies are required. If Helicobacter pylori is confirmed to be a factor in this respect, it will aid in the targeting of patients at greatest risk of developing ulcers in patients on long-term non-steroidal anti-inflammatory drugs. Those at greatest risk are elderly patients, especially females, smokers, patients with a previous ulcer history, severe or debilitating arthritis or who have other chronic diseases. The addition of Helicobacter pylori to this list and its subsequent eradication may improve the outlook for these patients and help in the effective targeting of patients at greatest risk who are on long-term non-steroidal anti-inflammatory drugs.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1996

Famotidine for the prevention of gastric and duodenal ulcers caused by nonsteroidal antiinflammatory drugs.

BACKGROUND: Acid suppression with famotidine, a histamine H2-receptor antagonist, provides protection against gastric injury in normal subjects receiving short courses of aspirin or naproxen. The efficacy of famotidine in preventing peptic ulcers in patients receiving long-term therapy with nonsteroidal antiinflammatory drugs (NSAIDs) is not known. METHODS: We studied the efficacy of two doses of famotidine (20 mg and 40 mg, each given orally twice daily), as compared with placebo, in preventing peptic ulcers in 285 patients without peptic ulcers who were receiving long-term NSAID therapy for rheumatoid arthritis (82 percent) or osteoarthritis (18 percent). The patients were evaluated clinically and by endoscopy at base line and after 4, 12, and 24 weeks of treatment. The evaluators were unaware of the treatment assignment. The primary end point was the cumulative incidence of gastric or duodenal ulceration at 24 weeks. RESULTS: The cumulative incidence of gastric ulcers was 20 percent in the placebo group, 13 percent in the group of patients receiving 20 mg of famotidine twice daily (P = 0.24 for the comparison with placebo), and 8 percent in the group receiving 40 mg of famotidine twice daily (P = 0.03 for the comparison with placebo). The proportion of patients in whom duodenal ulcers developed was significantly lower with both doses of famotidine than with placebo (13 percent in the placebo group, 4 percent in the low-dose famotidine group [P = 0.04], and 2 percent in the high-dose famotidine group [P = 0.01]). Both doses of famotidine were well tolerated. CONCLUSIONS: Treatment with high-dose famotidine significantly reduces the cumulative incidence of both gastric and duodenal ulcers in patients with arthritis receiving long-term NSAID therapy.

Adult↗

PubMed1996

Effect of omeprazole therapy on the survival of Helicobacter pylori, urease activity, and antral gastric histology in patients with duodenal ulcer.

BACKGROUND: Helicobacter pylori is associated with chronic active gastritis and peptic ulceration (PU). Omeprazole is a proton pump inhibitor that is effective in healing PU and reducing gastritis. Previously it has been found that omeprazole has some bacteriostatic activity against H. pylori both in vitro and in vivo and in inhibiting urease activity in vitro. Our aim was to evaluate the effect of omeprazole on H. pylori colonization of the gastric mucosa, urease activity in vivo, and the presence of associated gastritis in patients with duodenal ulcer (DU). MATERIALS AND METHODS: We studied 12 patients (7 men and 5 women, ages 22-68 yr) with Du larger than 5 mm in diameter with a positive CLOtest (Delta West Ltd., Australia). Omeprazole, 20 mg bid, was given for 8 weeks to each patient, patients were endoscoped at the end of this period to check for healing of DU, and repeat biopsies were obtained from the gastric antrum for histological analysis, CLOtest, and culture. RESULTS: DU healed completely in all patients. Likewise in all patients there was significant reduction in the urease activity, from 22.1 +/- 4.17 to 1.58 +/- 0.92 units/ml (p < .001; 95% confidence interval of the difference between means, 32.7-14.1), and reduced H. pylori density, from 1,403.46 +/- 128.23 to 422.5 +/- 172.39 colony-forming units (CFU) per milligram of tissue biopsy (p < .001; 95% confidence interval of the difference between means, 1,486.1-590.5). The numbers of H. pylori were reduced on the gastric mucosa after omeprazole therapy and disappeared in six patients, a result that correlated with a negative CLOtest reading after 24 hours. CONCLUSION: Omeprazole, 20 mg bid, is capable of reducing H. pylori numbers and urease activity in vivo. There was no significant reduction in the severity of antral gastritis in DU patients studied.

Adult↗

PubMed1996

Association of cytotoxin production and neutrophil activation by strains of Helicobacter pylori isolated from patients with peptic ulceration and chronic gastritis.

BACKGROUND: Helicobacter pylori is associated with neutrophil infiltration within the gastroduodenal mucosa. Neutrophil activation provides a major source of oxygen free radicals, which have been implicated in the pathogenesis of peptic ulceration. AIM: To investigate if cytotoxin producing strains of H pylori are associated with the generation of oxidative burst in polymorphonuclear neutrophils (PMNs). PATIENTS: 76 patients undergoing endoscopy of whom 45 had peptic ulcer and 31 chronic gastritis only were studied. METHODS: Strains of H pylori were cultured in Brucella broth. After 48 hours, bacteria were harvested by centrifugation and a bacterial suspension prepared as a stimulus for PMN oxidative burst using chemiluminescence. PMNs were prepared from health blood donors. To test the ability of strains to produce cytotoxin, culture supernatants of each were concentrated by polyethylene glycol and tested on cultured Vero cells for intracellular vacuolation. RESULTS: 30 of 45 (66.7%) peptic ulcer patients induced cell vacuolation versus nine of 31 (29%) strains from patients with chronic gastritis only (p < 0.01). Cytotoxin positive strains of H pylori regardless of the presence or absence of peptic ulcer displayed an increased induction of respiratory burst in PMNs compared with toxin negative strains from patients with chronic gastritis only (p < 0.05). Among the toxin negative strains, those from patients with peptic ulcer did not show a significant increase of the oxidative burst than those from patients without peptic ulcer (NS). CONCLUSION: Toxinogenicity of strains of H pylori seems to be correlated with neutrophil respiratory burst and peptic ulceration. The ability of some strains of H pylori to produce cytotoxin and to induce the oxidative burst in neutrophils may be important in the pathogenesis of peptic ulcer disease.

Adult↗

PubMed1996

Increased rates of duodenal mucosal protein synthesis in vivo in patients with untreated coelia disease.

BACKGROUND AND AIMS: A robust, reproducible method for the measurement of protein synthesis in the gastrointestinal mucosa was applied to investigate possible differences between the rate of duodenal mucosal protein synthesis in coeliac patients and normal control subjects. PATIENTS AND METHODS: Eight patients, means (SD) (51 (10) years, 57 (11) kg, 160 (6) cm) with newly diagnosed untreated coeliac disease and seven control subjects (48 (11) years, 71.5 (12) kg, 172 (10) cm) received primed, continuous, intragastric (IG) and intravenous (i.v.) infusions of L-[1-13C]leucine and L-[1-13C]valine after an overnight fast. Distal duodenal biopsy specimens were obtained at endoscopy performed after 240 minutes of infusion. Protein synthesis was calculated from protein labelling relative to intracellular free amino acid enrichment, after appropriate mass spectrometric measurements. RESULTS: Rates of duodenal protein synthesis were significantly greater in coeliac patients than in control subjects (i.v. tracer, coeliac v control, 3.58 (0.45) v 2.26 (0.22)%/h, p< 0.05; IG tracer, 6.25 (0.97) v 2.34 (0.52)%/h respectively, p < 0.01). The rates of mucosal protein synthesis calculated on the basis of the tracer infused via the intragastric route were higher in patients with coeliac disease than in control subjects. Tissue protein/DNA ratios were significantly reduced in coeliac patients (coeliac v control, 9.2 (1.6) mg/micrograms v 13.0 (2.2) mg/micrograms respectively, p < 0.05) suggesting smaller mucosal cell size in coeliac patients. CONCLUSIONS: Despite the villous atrophy and reduced cell size observed in coeliac disease, the rates of mucosal protein synthesis are considerably increased. These results suggest that a high rate of protein synthesis may be adaptive to a high rate of protein breakdown or mucosal cell loss in coeliac patients.

Adult↗

PubMed1996

Measurement of sugar probes in serum: an alternative to urine measurement in intestinal permeability testing.

The percentage dose of lactulose and mannitol excreted in urine after oral ingestion is used as a noninvasive method of assessing small intestinal permeability. The collection of incomplete or inaccurately timed urine samples can lead to errors in estimation of sugar probe molecules. We describe an HPLC method for the simultaneous determination of lactulose and mannitol in serum after oral ingestion of test sugars. We applied the test to healthy volunteers and to subjects undergoing jejunal biopsy for suspected gluten-sensitive enteropathy. The ratio of concentrations of lactulose and mannitol in serum discriminated well between subjects with a normal biopsy and those with villous atrophy, discrimination being best at 90 min postdose. The results agree well with lactulose:mannitol ratios determined in urine (r= 0.88), and the two methods can be used interchangeably. The determination of mannitol and lactulose in serum provides an acceptable alternative to urine collection and may be particularly useful in young children. It also reduces the time spent on the investigation from 5 h to 90 min.

Biopsy↗

PubMed1995

Use of a stable copper isotope (65Cu) in the differential diagnosis of Wilson's disease.

1. 65Cu/63Cu stable-isotope ratios have been measured in blood serum after oral administration of the stable isotope 65Cu. The incorporation of the isotope into the plasma protein pool was followed at various times for up to 3 days. The resulting patterns of enrichment in healthy control subjects, in Wilson's disease patients and in heterozygotes for the Wilson's disease gene, were similar in appearance to those found by others using copper radioactive isotopes. After an initially high enrichment at 2 h after dosage, the Wilson's disease cases, in contrast to the control subjects, did not show a secondary rise in isotope enrichment of the plasma pool after 72 h, demonstrating a failure to incorporate copper into caeruloplasmin. The Wilson's disease heterozygotes had variable degrees of impairment of isotope incorporation, not always distinguished from those of control subjects. 2. The stability of the isotope also permits the copper tracer to be followed for a longer period. Ten healthy subjects were studied for over 40 days, allowing the biological half-time of an oral dose of copper to be determined (median 18.5 days, 95% confidence interval 14-26 days). Known heterozygotes for the Wilson's disease gene were found to have a significantly increased biological half-time for removal of copper from the plasma pool (median 43 days, 95% confidence interval 32-77 days). 3. The incorporation of 65 Cu in patients with diseases of the liver (other than Wilson's disease) was found to be similar to that in control subjects, aiding differential diagnosis.

Adolescent↗

PubMed1995

Mucosal erosions in longterm non-steroidal anti-inflammatory drug users: predisposition to ulceration and relation to Helicobacter pylori.

The importance of erosions in longterm non-steroidal anti-inflammatory drug (NSAID) users, their relevance to ulceration and their relation to Helicobacter pylori are unclear. This study assessed the incidence of peptic ulcers in the presence or absence of erosions or H pylori in a group of longterm NSAID users (n = 50), undergoing endoscopy at 0, 4, 12, and 24 weeks while continuing with NSAIDs. Ulcers diagnosed at baseline endoscopy were excluded. Ulcers developed in nine of 23 patients (39%) with pre-existing erosions compared with six of 27 (22%) without erosions (p < 0.05). The group infected with H pylori (n = 30) had a total of 18 patients (60%) with erosions, a total of 12 ulcers (40%), and eight ulcers (27%) complicating previous erosions, compared with five (25%, p < 0.01), three (15%, p < 0.05), and one (5%, p < 0.01) respectively in patients not infected with H pylori (n = 20). Ulcer development was not influenced by the initial number of erosions but strongly associated with H pylori positive duodenal erosions. It is concluded that ulcers are more likely to develop in longterm NSAID users who have mucosal erosions or H pylori, or both.

Adult↗

PubMed1995

Gut mucosal protein synthesis measured using intravenous and intragastric delivery of stable tracer amino acids.

We measured the rates of mucosal protein synthesis during the simultaneous delivery of [1-13C]leucine and [1-13C]valine delivered either intragastrically or intravenously to investigate any influence of the route of supply of the tracers. Dependent on the route, there were marked differences in the gradient of labeling between the plasma and intramucosal leucine and valine; i.e., for intravenous tracers the ratio was 1.73 +/- 0.16, but for intragastric tracers it was 0.65 +/- 0.12 (P < 0.05). Incorporation of intravenous tracer into mucosal protein was linear with time, and irrespective of tracer route, the calculated fractional rates of protein synthesis were identical when based on the intracellular labeling of the leucine or valine tracer, i.e., with intravenous 2.58 +/- 0.32%/h and with intragastric 2.45 +/- 0.36%/h. The results demonstrate that a robust and reproducible method of measurement of gastrointestinal mucosal protein synthesis has been developed and that use of either intragastric or intravenous routes of tracer administration gives comparable results. The high rates measured suggest that the gastrointestinal mucosa contributes substantially to whole body protein synthesis in normal healthy subjects.

Adult↗

PubMed1994

Continuous axillary nerve block for chronic pain.

Continuous axillary nerve block was used to relieve pain after a chemical burn to the arm in a child on mechanical ventilation after liver transplantation. The analgesia was sufficient to replace parenteral analgesia and allow extubation.

Aprotinin↗

PubMed1994

Predicting NSAID related ulcers--assessment of clinical and pathological risk factors and importance of differences in NSAID.

Although ulcers are often associated with non-steroidal anti-inflammatory drugs (NSAIDs) little is known about the feasibility of predicting their development in patients taking NSAIDs. In addition, the ulcerogenic potentials of the newer NSAIDs, taken on long term basis, have not been compared with those of more established preparations. The aim of this study was to identify the clinical and pathological characteristics of patients at a higher risk of NSAID induced ulcers, measure the ulcerogenic potential of a variety of NSAIDs, and test the effect of these potentials on the predictability of ulceration. Altogether 190 long term NSAID users were studied. The presence of abdominal complaints, previous history of ulcers, arthritis related physical disability, anaemia, gastritis, and Helicobacter pylori status were all assessed as possible risk factors. NSAIDs were classified into established drugs (group I), and newer agents (group II). Group I included naproxen, indomethacin, diclofenac, ketoprofen, piroxicam, and flurbiprofen. Group II included fenbufen, nabumetone, ibuprofen, etodolac, azapropazone, and tiaprofenic acid. Of 63 ulcers identified in the study group, 51 (81%) were seen in group I NSAID patients (51 of 132, 39%) compared with 12 ulcers in group II (12 of 58, 21%), p < 0.02; estimated relative risk (ERR): 2.41). In group I, 25 ulcers were found in 38 patients with abdominal pain (25 of 38, 66%, p < 0.01, ERR: 5.03); 18 in 25 (72%) patients with a previous history of ulcers (p < 0.001, ERR: 5.77), 26 in 44 (59%) patients with debilitating arthritis (p < 0.001, ERR 3.64), and 35 in 73 (48%) patients with H pylori associated gastritis (p < 0.01, ERR: 2.48). The presence of these factors in group II patients did not influence the risk of ulceration. Group I NSAIDs were more likely to be associated with chemical gastritis and to intensify H pylori related damage. Although silent ulcers are not uncommon in patients taking NSAIDs, recognition of the risk factors might helps predict a significant number (up to 81%), especially in those receiving group I NSAIDs.

Aged↗

PubMed1994

Oesophageal histology in long term users of non-steroidal anti-inflammatory drugs.

AIMS: To study the oesophageal histological changes in long term users of non-steroidal anti-inflammatory drugs (NSAIDs) compared with patients not receiving these drugs. METHODS: Ninety eight patients were studied, 53 of whom had taken NSAIDs for three years; 45 had not. Oesophageal biopsy specimens were taken from healthy-looking mucosa in the lower third of oesophagus. The papillary length, the thickness of the basal cell layer, and the intensity of cells infiltrating the epithelium were all assessed blind. RESULTS: The NSAID group included four (7%) cases of papillary elongation and two (4%) cases of basal cell hyperplasia, compared with 13 (29%; p < 0.01) and eight (18%; p < 0.02), respectively, in patients not taking NSAIDs. The total histological scores were also lower in patients treated with NSAIDs. CONCLUSION: Long term NSAID users have fewer oesophageal histological abnormalities than patients not receiving NSAIDs. Macroscopic damage related to NSAID use is, therefore, unlikely to require pre-existing histological oesophagitis for its development.

Aged↗

PubMed1994

A retrospective assessment of the clinical value of jejunal disaccharidase analysis.

BACKGROUND: The measurement of jejunal disaccharidases is used by several gastroenterologists when investigating suspected small-bowel disease. The clinical value of this analysis is assessed. METHOD: The histology and disaccharidase results in 1585 jejunal biopsy specimens were reviewed retrospectively. RESULTS: Disaccharidase and histology results concurred in most cases (72%). However, disaccharidases were an insensitive indicator of small-bowel disease: low levels were found in only 65% of coeliac patients with villous atrophy, 15% of patients with giardiasis, and 6% of patients with villous atrophy associated with non-coeliac histology. Low disaccharidase levels were sometimes found in patients with normal histology (1.6%) and when biopsy specimens were unwittingly taken from non-jejunal sites (1.4%). Isolated low lactase activities were found in 3.2%. Usually this finding was not clinically relevant because patients had no symptoms of lactose intolerance (38%), had another diagnosis that responded to appropriate treatment (8%), or had no response to a low-lactose diet (14%). In 16 patients sucrase activities were markedly low, and this investigation proved central to the diagnosis of sucrase-alpha-dextrinase deficiency, which was subsequently confirmed in 9. CONCLUSION: Jejunal disaccharidases are clinically useful only in the diagnosis of sucrase-alpha-dextrinase deficiency. We recommend that their measurement be reserved for the investigation of patients suspected of having this condition.

Adult↗

PubMed1994

Evaluation of three different techniques used to measure chest wall movements in children.

Several techniques exist for assessing chest wall movements in children, that incorporate different measurement principles. Although the output from such devices appears very similar, the comparability of data from different devices needs to be evaluated. We have investigated the simultaneous measurement of chest wall movement using three different devices in 12 children recovering from intensive care. The devices used were inductance plethysmography (assessing thoracic cross-sectional area), magnetometers (assessing thoracic diameter), and a Hall device strain guage (assessing thoracic circumference). Measurements of respiratory timing and of phase angle between rib cage and abdomen in these patients showed a close agreement between devices in ventilated patients. However, occasional inconsistencies occurred in patients who were breathing spontaneously. We suggest that it may not always be appropriate to directly compare data on chest wall movements in children recorded using different measurement techniques. The best method of measurement varies with the clinical picture.

Child↗

PubMed1994

Intestinal permeability in patients with Crohn's disease and their first-degree relatives.

OBJECTIVE: To measure small intestinal permeability in a group of patients with Crohn's disease in clinical remission and their apparently healthy first-degree relatives. METHODS: Administration of 51Cr-labeled EDTA and subsequent measurement of its excretion in a 24-h urine collection. RESULTS: Excretion of 51Cr-EDTA was not elevated in either the patients or in first-degree relatives. CONCLUSION: Intestinal permeability to 51Cr-EDTA is not raised in patients with Crohn's disease in clinical remission or in their healthy first-degree relatives.

Chromium Radioisotopes↗

PubMed1993

The effect of variations in positive end expiratory pressure on gas exchange in ventilated children with liver disease.

The effect of varying the positive and expiratory pressure (PEEP) level during mechanical ventilation has been assessed in ten children with liver disease, mean age 3.8 years. PEEP was increased 3 cmH2O above the child's original (baseline) PEEP level and then decreased either by 3 cmH2O below the baseline or to 0 cmH2O. In all ten children increasing the PEEP above the baseline improved oxygenation; in the group overall the median PaO2 increased from 90 mmHg to 97 mmHg (P < 0.01). In eight of ten children decreasing the PEEP level below the baseline resulted in a deterioration in oxygenation; in the group overall the median PaO2 decreased from 91 mmHg to 82 mmHg (P < 0.05). Changes in PEEP levels, however, did not result in clinically significant alterations in PaCO2, heart rate or blood pressure. We conclude that modest increases in PEEP are well tolerated in children with liver disease and result in an improvement in oxygenation.

Carbon Dioxide↗

PubMed1993

Effects of dietary gluten elimination in patients with recurrent minor aphthous stomatitis and no detectable gluten enteropathy.

Fifty patients with a history of minor recurrent aphthous stomatitis were entered into a 6-month double-blind controlled trial of a gluten-free diet. After hematologic and biochemical investigations and jejunal biopsy, one half of the group was given a gluten-free diet; the other half served as controls and received a gluten-free diet supplemented by gluten given blind (control diet). Twenty-three patients completed the trial, 11 patients on a gluten-free diet, 12 on the control diet. Four of the 11 on the gluten-free diet and 7 of the 12 on the control diet reported significant benefit in terms of minor recurrent aphthous stomatitis, but there was no statistical difference between the responses. The results fail to support studies that report widespread benefit in aphthae of gluten withdrawal and suggest simply a marked placebo response in the condition.

Adolescent↗

PubMed1993

The Health Assessment Questionnaire as a predictor of non-steroidal peptic ulceration.

To assess the possibility of a relationship between the degree of physical disability in arthritic patients and non-steroidal peptic ulceration, patients were endoscoped immediately after performing their arthritic functional assessments. The Health Assessment Questionnaire was used and patients were classified into three main groups: I, scoring 0-1; II, 1.1-2; and III, 2.1-3. Ulcers, found in 36 out of 89 patients studied (36/89, 40%), were distributed as follows: 15/22 (68%) in group III compared with 9/28 (32%) in group I (chi 2 = 5.2, P < 0.02), and 12/39 (31%) in group II (chi 2 = 7.24, P < 0.01). Patients with debilitating arthritis appear to have a higher prevalence of non-steroidal peptic ulceration. This finding might be relevant to the process of selecting patients for prophylactic anti-ulcer therapy.

Adult↗