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Biomedical subjects

R Eliakim

Publications and source records attributed to R Eliakim.

At least 19 recordsLinked to original sources
PubMed1998

Budesonide versus prednisone in the treatment of active Crohn's disease. The Israeli Budesonide Study Group.

BACKGROUND & AIMS: Budesonide (BUD) is a potent steroid that undergoes extensive first-pass metabolism. BUD incorporated in a pH-dependent formulation has been proposed as an alternative treatment for Crohn's disease (CD). The aim of this study was to compare the efficacy and safety of BUD and prednisone (PRED) in the treatment of active CD involving the terminal ileum and/or the colon. METHODS: Patients with mild to moderately active CD were included in a randomized, double-blind, double-dummy controlled trial. Patients received either 9 mg BUD once daily for 8 weeks or 40 mg PRED once daily for the first 2 weeks tapered gradually to 5 mg/day by the end of the study. Disease activity, quality of life, and laboratory parameters were recorded. RESULTS: One hundred patients received BUD, and 101 patients received PRED. By intention-to-treat analysis, treatment efficacy defined as Crohn's Disease Activity Index of <150 at completion was 51% and 52.5% for the BUD and PRED groups, respectively. Twice as many responded to treatment with no side effects in the BUD compared with the PRED group (30% vs. 14%) (P = 0.006). Most of the decrease in CDAI scores occurred during the first 2 weeks. CONCLUSIONS: BUD is as effective as PRED in the treatment of CD involving the terminal ileum and right colon. BUD has significantly fewer steroid-related adverse reactions.

Adult↗
PubMed1998

Direct determination of colonic nitric oxide level--a sensitive marker of disease activity in ulcerative colitis.

OBJECTIVE: In active ulcerative colitis, colonic nitric oxide (NO) generation is enhanced and probably has an important role in its pathogenesis. We tested the reliability of an NO electrode in monitoring colonic NO levels in ulcerative colitis patients and control subjects and its possible usage as a marker of disease activity. METHODS: Colonic NO level was determined by the NO detection system model NO-501 (InterMedical, Nagoya, Japan). The working electrode was inserted into a 7-mm diameter polyvinyl tube and introduced at a distance 6 cm from the anus. In each subject sigmoidoscopy was performed and mucosal biopsies were obtained. NO synthase (NOS) activity was determined by monitoring the conversion of 3H-arginine to citrulline. RESULTS: Colonic NO level is significantly increased in patients with active ulcerative or Crohn's colitis--more than 2-fold higher than in control subjects. There was good correlation between colonic NO level and NOS activity and the clinical and endoscopic indices of disease activity. CONCLUSION: Direct determination of colonic NO level is convenient, and reliable, and may help to monitor disease activity in ulcerative colitis.

Adult↗
PubMed1998

Femoral neck osteopenia in patients with inflammatory bowel disease.

OBJECTIVE: The mechanism of bone loss in patients with inflammatory bowel disease (IBD) is not completely understood. The aim of this study was to assess indices of bone turnover and bone mineral density (BMD) in the lumbar spine and femoral neck in IBD patients. METHODS: Sixty-three patients with Crohn's disease and 41 with ulcerative colitis were studied. Serum bone-specific alkaline phosphatase (B-ALP), osteocalcin, parathyroid hormone (PTH), 25 hydroxyvitamin D, interleukin-6 (IL-6), and urinary N-telopeptide cross linked type 1 collagen (NTX) were determined. BMD of the lumbar spine and femoral neck was determined by dual x-ray absorptiometry in 59 patients. RESULTS: In the femoral neck 42% of the patients had osteopenia (-2.5 SD < BMD T score < -1 SD) and another 41% had osteoporosis (BMD T score < -2.5). In the spine 34% of the patients had osteopenia and additional 42% had osteoporosis. BMD T scores were lower in the femoral neck compared to the spine. Reduced BMD was unrelated to gender, disease type, lifetime corticosteroid dose, but inversely correlated with disease duration (r = -0.36, p < 0.05). Serum IL-6 was higher in IBD patients compared to controls. A reduced level of osteocalcin, a marker of bone formation, was present in 7% of patients and an increase in NTX, a marker of bone resorption, in 25% of them. Osteoporotic IBD patients (spine or hip BMD T score < -2.5) had increased serum IL-6, osteocalcin and PTH level compared to nonosteoporotic patients. CONCLUSIONS: There is a high prevalence of reduced BMD at the spine and femoral neck in IBD patients, which is more severe in the hip. Bone turnover in osteoporotic IBD patients is associated with an increase in osteocalcin, PTH and IL-6. IL-6 may play a role in the pathogenesis of bone loss in IBD.

Adult↗
PubMed1997

[Cyclosporin for severe ulcerative colitis].

In recent years there have been numerous reports of successful treatment of resistant ulcerative colitis with cyclosporin. A series of 9 patients with moderate to severe active ulcerative colitis was treated with cyclosporin between September 1993 and October 1994. All 9 had failed to respond to conventional therapy, including salazopyrine and intravenous corticosteroids. They underwent colonoscopy and after contraindications to therapy were ruled out, received intravenous cyclosporin, 4 mg/kg/day for 7-10 days. They were discharged on oral cyclosporin with average serum levels maintained at 200 ng/ml. Response was assessed using the clinical score system of Schroeder et al. 2 out of 9 patients (22%) responded with full clinical remissions lasting more than 6 months. 6 patients had partial responses to the intravenous therapy, but symptoms resumed shortly after its cessation. Factors predicting favorable response to cyclosporin therapy were a shorter duration of disease with a fulminant clinical course. The success rate was less than that reported in the literature, possibly because of comparatively low serum cyclosporin levels. Potential complications of therapy and high cost preclude the routine use of cyclosporin in ulcerative colitis. Larger controlled studies are required to assess its efficacy and safety. Until such studies are available, cyclosporin may be tried in poor surgical risks or those not yet ready psychologically for total colectomy.

Administration, Oral↗
PubMed1997

A more liberal approach to the surgical treatment of Crohn's disease.

BACKGROUND: Surgery for Crohn's disease is not intended for cure, but rather to relieve symptoms and treat complications. Perioperative morbidity, the fear of creating short bowel syndrome, and the tendency of the disease to recur convinced many physicians to refer their Crohn's patients for surgery only when life-threatening complications occur. METHODS: This is a retrospective analysis of 47 patients operated on for Crohn's disease between 1989 and 1994. Twenty-six patients were operated on for "classic" indications ("classic" group) and the other 21 were operated on to improve their quality of life ("quality" group). RESULTS: There was no operative or postoperative mortality during a mean follow-up period of 50 (27 to 84) months. All major postoperative complications occurred only in patients operated on for the classic indications (four abscesses, two fistulas, one wound dehiscence, and two small bowel obstructions). During the follow-up period, a total of 13 patients (50%) in the classic group and only 5 patients (24%) in the quality group required reintroduction of medical therapy or additional operations for exacerbations and complications of Crohn's disease. CONCLUSIONS: Our data suggest that surgical intervention intended to improve the quality of life for Crohn's disease patients is safe and effective for carefully selected patients. It does improve quality of life, may prevent life-threatening complications, and offers a lower recurrence rate following surgery.

Adolescent↗
PubMed1997

Anti-thyroid drugs decrease mucosal damage in a rat model of experimental colitis.

BACKGROUND: Methimazole, an anti-thyroid drug, was recently found to be useful in the treatment of systemic lupus erythematosus and other autoimmune diseases. Moreover, decreased thyroid hormone production is associated with a variety of immunological manifestations, such as reduced activation of CD4+ cells, increased CD8+ cell activity and reduced soluble IL-2 receptors. In the present study we examined the effects of methimazole and propylthiouracil on a rat model of experimental colitis. METHODS: Colitis was induced by intracolonic administration of 30 mg trinitrobenzene sulphonic acid (TNB). Two weeks prior to induction of colitis, rats were treated by either methimaziole (0.04%) or propylthiouracil (0.01%) in drinking water after a week of free access to water. Rats were sacrificed 48 h or 7 days after induction of colitis. The colon was isolated, rinsed with ice-cold water and weighed. Damage was assessed both macroscopically and microscopically and myeloperoxidase (MPO) activity determined. RESULTS: All treated rats were hypothyroid as manifested by a significant elevation of thyroid stimulating hormone (TSH), by comparison with the control groups (mean -1.82 +/- 0.40 versus 0.11 +/- 0.02 mmol/L, respectively). The inflammatory response elicited by TNB resulted in severe mucosal damage 48 h after damage induction, which persisted for 7 days. Pre-treatment with either methimazole 0.04% or propylthiouracil 0.01% significantly decreased mucosal damage macroscopically (lesion area, lesion score and segmental weight) microscopically and also significantly decreased MPO level at both time points (P < 0.01). CONCLUSIONS: Methimazole and propylthiouracil significantly reduce mucosal damage and colonic weight in a rat model of colitis. The mode by which they do so remains to be studied.

Animals↗
PubMed1997

Brucellosis and the gastrointestinal tract. The odd couple.

Though pathogenetically qualifying as an enteric fever, the gastroenterological manifestations of Brucella in humans are relatively uncommon. We present a typical case of Brucellosis with gastrointestinal symptoms and review these by organ involvement, ranging from the mild nonspecific, such as diarrhea and abdominal pain, to the pathologically distinct hepatic lesions, and to the rare colonic, pancreatic, and peritoneal involvement. The limited indications for diagnostic procedures, such as endoscopy and liver biopsy are discussed.

Abdominal Pain↗
PubMed1997

Assessing disease activity in Crohn's disease--are we there yet?

Many attempts have been made over recent years to assess accurately disease activity in Crohn's disease. We review some of these attempts, giving particular emphasis to the combination of serum levels of proinflammatory cytokines (interleukin-6, tumour necrosis factor alpha, recombinant interleukin-2 and acid alpha-1-glycoprotein).

Biomarkers↗
PubMed1997

Isolation and characterization of surfactant-like particles in rat and human colon.

The source of a phospholipid-rich layer recovered from the surface of the mammalian colon has been obscure. This report describes the isolation of a low-density membrane from the surface of rat and human colons (d = 1.07-1.08 g/ml), with a low cholesterol-to-phospholipid ratio and phosphatidylcholine as its major phospholipid. Electron microscopy shows unilamellar and partially coiled membranes. Compared with microvillous membranes isolated from underlying mucosa, this extracellular membrane is enriched for tissue-unspecific alkaline phosphatase and surfactant protein A. It does not contain small intestinal marker proteins (intestinal alkaline phosphatase and sucrase-isomaltase). The human membrane contains only traces of the colonic microvillous membrane marker, carcinoembryonic antigen. Antiserum against the rat colonic membrane does not recognize colonic microvillous membrane or small intestinal surfactant-like particle proteins. Antiserum against human colonic membrane identifies one protein in the surfactant-like particle from the adjacent small intestine and two proteins in the colonic microvillous membrane. These data show that the colonocyte microvillous membrane is covered by another membrane with a different protein composition. Enrichment for surfactant protein A suggests that this colonic membrane is another example of a surfactant-like particle sharing proteins with pulmonary surfactant.

Alkaline Phosphatase↗
PubMed1997

Methotrexate in chronic active Crohn's disease: a double-blind, randomized, Israeli multicenter trial.

BACKGROUND: At present only one large controlled study has indicated that parenteral methotrexate may be effective in chronic active Crohn's disease (CD). AIM: To evaluate the effectiveness of oral methotrexate in chronic steroid-dependent CD. PATIENTS: Patients with active CD, who have received steroids and/or immunosuppressives for at least 4 months during the preceding 12 months and with a current Harvey-Bradshaw index of > or = 7 were studied. METHODS: Methotrexate (12.5 mg weekly) or 6-mercaptopurine (50 mg daily), or placebo were given during the 9 months of the trial in addition to steroids and 5-aminosalicylic acid as clinically indicated. RESULTS: Eighty-four patients were included (methotrexate, 26 patients; 6-mercaptopurine, 32 patients; placebo, 26 patients). The proportion of patients entering first remission as well as the proportions of patients relapsing after first remission were not significantly different between the groups. The mean Harvey-Bradshaw index and the mean monthly steroid dose were also similar. However, when each patient was evaluated as his or her own control, the reduction in steroid dose, the general well being, and the reduction in abdominal pain were significantly better in the methotrexate treated patients. CONCLUSIONS: Methotrexate at a weekly oral dose of 12.5 mg was found to be moderately better than 6-mercaptopurine and placebo in patients with chronic active CD.

Abdominal Pain↗
PubMed1997

Open-access endoscopy of the upper gastrointestinal tract: is it indicated and efficient? Retrospective and prospective studies in an Israeli population.

Open-access endoscopy has recently gained popularity in referring patients for endoscopic procedures. Retrospective (looking into patients' medical files) and prospective studies (using 2 different questionnaires, and evaluating a selection system) were conducted, comparing the efficacy of open-access endoscopy for patients referred by either family practitioners or gastroenterologists. In the retrospective study, 673 patients (mean age 48.8 years, male-58%) underwent upper gastrointestinal endoscopy. The main indications for upper endoscopy were epigastric pain (71%), heartburn (18%) and vomiting (13%). Severe endoscopic findings were not different between the study groups. Normal or mildly abnormal findings were diagnosed in 75% of patients in both groups. In the prospective study, 361 patients were referred for upper endoscopy (mean age 50.2 years, male-58%). Although there were significantly (p < 0.01) fewer normal and more mild endoscopic findings in the patients referred by gastroenterologists, as compared with family practitioners, there was no difference in the clinically significant (severe) endoscopic findings. Previous ulcer, smoking, gender, age and nocturnal pain were predictive for severe endoscopic findings. There was a linear correlation between the severity of the scoring system and the endoscopic findings. The results of the present study, which reveal nonsignificant differences in the indications for and the findings of endoscopies, indicate that selection of patients for endoscopy can be safely done by family practitioners. In order to reduce the number of referred patients with no gastrointestinal pathology, a better scoring system to detect at-risk patients should be developed.

Aged↗
PubMed1996

Methotrexate in chronic active ulcerative colitis: a double-blind, randomized, Israeli multicenter trial.

BACKGROUND & AIMS: Uncontrolled studies have suggested that methotrexate may be effective in patients with active ulcerative colitis. The aim of this study was to evaluate the effectiveness of oral methotrexate in chronic steroid-dependent ulcerative colitis in a randomized, double-blind multicenter trial. METHODS: Patients with active ulcerative colitis who have received steroids and/or immunosuppressives for at least 4 months during the preceding 12 months with a current Mayo Clinic score of > or = 7 were included in the study. Methotrexate (12.5 mg) or placebo was added to their treatment once weekly for 9 months. RESULTS: Sixty-seven patients were included (methotrexate, 30 patients, placebo, 37 patients). The proportion of patients entering first remission (methotrexate, 46.7%; placebo, 48.6%), the time to reach first remission (methotrexate, 4.1 +/- 1.9 months; placebo, 3.4 +/- 1.7 months), as well as the proportions of patients having a relapse after first remission (methotrexate, 64.3%; placebo, 44.4%) were not significantly different between the two groups. The mean Mayo Clinic score, the mean monthly steroid dose, and the proportion of abnormal laboratory results during the study were also similar. CONCLUSIONS: Methotrexate at a weekly oral dose of 12.5 mg was not found to be better than placebo in the induction or maintenance of remission in patients with chronic active ulcerative colitis.

Administration, Oral↗
PubMed1996

Abundance of surfactant-like particles reflects mucosal integrity in patients with peptic ulcer disease.

BACKGROUND: Surfactant-like particles, normal products of the human enterocyte, are released into the lumen and secreted into blood. AIMS: To assess their role as markers for mucosal functional integrity, this study examined their content in biopsy specimens and serum of patients with duodenal ulcer disease, compared with non-diseased control subjects. PATIENTS: Endoscopic biopsy specimens were taken 1-2 cm from areas of active inflammation or ulcer (peptic ulcer patients) or just beyond the duodenal bulb (normals) in 35 consecutive subjects. METHODS: After staining for phospholipid, extracellular and intracellular particles were counted on transmission electron micrographs of coded specimens. Serum was obtained from 24 patients, and densitometry of the 59 kDa band detected on western blot by antiserum against human jejunal particle was measured. RESULTS: Normal duodenum (n = 15) contained more particles (44 (4.7)) particles/block, mean (SD) than active duodenal ulcer (n = 13, 17 (3.9)) or gastritis/duodenitis patients (n = 4, 9 (2.7)). Three patients examined after healing of duodenal ulcers showed abundant particles (n = 3, 67 (2.2)). Similarly, the 59 kDa band was decreased in serum of patients with active peptic ulcer disease (n = 11, 0.25 (0.04) absorbance units) compared with normal patients (n = 10, 0.40 (0.03)) or healed ulcers (n = 3, 0.62 (0.04)). There was good correlation between morphological mucosal particle abundance and particle protein content of serum assayed from the same patients (r = 0.831). These changes were independent of Helicobacter pylori status. CONCLUSION: The mucosal and serum content of surfactant-like particles may reflect general mucosal integrity of the enterocytes from which they are derived.

Adult↗