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Biomedical subjects

S Reif

Publications and source records attributed to S Reif.

At least 37 records · Page 2Linked to original sources
PubMed2001

Bioequivalence investigation of high-dose etoposide and etoposide phosphate in lymphoma patients.

PURPOSE: To compare etoposide pharmacokinetics following administration of high-dose etoposide and etoposide phosphate, a water-soluble prodrug of etoposide. Bioequivalence was assessed using a two-treatment randomized crossover design. METHODS: Ten patients with high-risk or relapsed lymphoma were treated with a sequential high-dose chemotherapy. They were randomized to receive either 3 x 400 mg/m2 etoposide or an equimolar amount of etoposide phosphate (as 1-h infusions on three consecutive days) in the first course and the alternative drug in the second course. Serial plasma and ultrafiltered plasma samples were collected and analysed for etoposide by a reversed-phase HPLC method with UV and electrochemical detection. Pharmacokinetic parameters were estimated using a two-compartment model. Bioequivalence was assessed calculating the 90% confidence intervals (CI) for the ratios of the geometric means of AUC(0-infinity) and additionally of Cmax of etoposide derived from etoposide phosphate relative to etoposide in plasma and ultrafiltered plasma as point estimates (level of significance alpha < 0.05). RESULTS: Pharmacokinetic parameters of etoposide were comparable in both treatment arms except that terminal half-life was significantly shorter and apparent Vss in ultrafiltered plasma was significantly larger following administration of the prodrug. The point estimates for AUC(0-infinity) of etoposide derived from etoposide phosphate relative to etoposide were 102.9% and 88.4% for plasma and ultrafiltered plasma, respectively. The 90% CIs were in the range from 80% to 125% where bioequivalence can be assumed. The point estimates of Cmax on day 3 of chemotherapy were 96.5% and 81.7% in plasma and ultrafiltrate with the 90% CI in ultrafiltered plasma being out of the range from 80% to 125%. CONCLUSION: With respect to total drug exposure, represented by AUC(0-infinity), high-dose etoposide phosphate is bioequivalent to high-dose etoposide.

Adult↗
PubMed2001

Effects of current cigarette smoking on clinical course of Crohn's disease and ulcerative colitis.

Cigarette smoking worsens Crohn's disease (CD) but ameliorates ulcerative colitis (UC). In Israel, where there is no epidemiological association of smoking with CD, we examined the effects of current smoking on the course of CD and UC. Patients at nine public hospitals completed a questionnaire detailing their smoking history, disease course and treatments; subjects altering their smoking habit after the onset of disease were excluded. Sixty-four smokers and 144 nonsmokers had CD, and 34 smokers and 158 nonsmokers had UC. No differences were found between CD smokers and nonsmokers for hospitalizations, operations, and requirement for corticosteroid and immunosuppressive treatment. By contrast, UC smokers had less extensive disease than nonsmokers (P < 0.02) and fewer hospitalizations (P = 0.01) and operations (P = 0.025). Our results agree with a minority of studies showing no adverse effect of smoking on the course of CD, and confirm the protective effect of smoking in UC.

Adolescent↗
PubMed2001

Appendectomy is more frequent but not a risk factor in Crohn's disease while being protective in ulcerative colitis: a comparison of surgical procedures in inflammatory bowel disease.

OBJECTIVE: Appendectomy was shown to be protective in patients with ulcerative colitis (UC). There are fewer data in Crohn's disease (CD). Other operations were less studied. The aim of this study was to investigate the prevalence of appendectomy, cholecystectomy, and tonsillectomy, including their timing, in patients with inflammatory bowel disease in comparison to controls. METHODS: Two hundred seventy-one patients with UC and 260 with CD, 475 clinic controls, and 428 community controls were interviewed. RESULTS: Appendectomy was found in 5.5% patients with UC, in 11% of clinic controls (p < 0.05), and 7.7% of community controls (p = not significant). The differences were more significant for appendectomy before onset of disease. Appendectomy was performed in 19.2% of patients with CD, in 10.9% of clinic controls, and in 10.1% of community controls (p < 0.01). However, there were no significant differences when only appendectomy before onset of disease was considered. Cholecystectomy was found in 1.5% of patients with UC, in 6.1% of clinic controls (p < 0.01), and in 4.5% of community controls (p = not significant). The difference remained significant when confined to operations performed before disease onset. No such difference was found in patients with CD. No significant difference was found in the prevalence of tonsillectomy between patients and controls. CONCLUSIONS: Appendectomy is protective in UC; it is more frequent, but not a risk factor in CD. The role of cholecystectomy should be investigated further.

Adult↗
PubMed2001

The effect of Medicaid managed care on rural public health departments.

Medicaid managed care programs are now operating in more than half of all rural counties in the United States. This study examines how rural health departments that have historically provided clinical services have responded to and been affected by the implementation of Medicaid managed care. To the extent that rural health departments have changed, the effect of this change on the health department and the rural populations that these providers serve is assessed. Site visits were made to four rural public health departments in each of five study states, for a total of 20 case studies. At each site, in-person interviews of county public health department directors were conducted using semistructured interview protocols. In recent years, the majority of health departments decreased or discontinued provision of well-child services, causing many to lose Medicaid revenue. None of the health departments appeared to be in danger of closing, but most lost income security. Medicaid managed care appeared to have increased the number of children with medical homes in the private sector, but adequacy and continuity of care remains an issue. Privatizing Medicaid managed care has not decreased fragmentation, as public health functions such as tracking and screening represent an important facet of comprehensive health services for poor rural populations.

Administrative Personnel↗
PubMed2001

[The effect of gastro-esophageal reflux therapy on respiratory diseases in children].

UNLABELLED: In order to examine the effect of reflux therapy on Hyper Reactive Airway Disease (HRAD) and apnea severity, 107 children, 78 with HRAD and 29 with apnea, underwent pH monitoring in the Pediatric Surgery Unit of Wolfson Hospital and the Dana Children's Hospital during the years 1995-1998. Pathological reflux was defined by means of the Boix-Ochoa and RI (Reflux Index) scores. In patients with positive reflux, anti-reflux treatment was initiated. Prior to and following pH monitoring, the respiratory status of all patients (both with and without reflux) was evaluated by a pediatric pulmonologist employing commonly used scores to determine severity. RESULTS: Subject age ranged between one day and 15 years (mean: 15.44 +/- 29 months, median: 6.37 months). In HRAD, following anti-reflex treatment the reflux positive group showed a significant score improvement, from an average of 2.9 +/- 1.1 units to 1.54 +/- 1.2 units (p < 0.0001); a decrease in the number of patients treated with oral corticosteroids (p < 0.01); a close to significant decrease (p = 0.069) in the average dose of inhaled corticosteroids; and a decrease in the number of patients using bronchodilators (p = 0.042). The reflux-negative group, not treated for reflux, displayed no significant improvement, with only a decrease in the severity scores from 2.44 +/- 1.0 to 1.78 +/- 1.2 units (p = 0.14), and no change on any of the other parameters. In apnea, all patients improved, from an average score of 2.34 +/- 0.77 to 0.03 +/- 0.19 units (p < 0.0001), with no significant difference between the reflux positive and the reflux negative groups. In view of these findings, it is postulated that anti-reflux therapy may have an additive effect on HRAD severity, beyond that of spontaneous respiratory improvement. We therefore find it appropriate for every severe HRAD patient (frequent exacerbations or high corticosteroid dose) to undergo pH monitoring in order to treat those with proven reflux. In respect to apnea, we cannot attribute any significance to the existence of reflux or to anti-reflux treatment.

Adolescent↗
PubMed2001

[Treatment of Crohn's disease with anti TNF alpha antibodies--the experience in the Tel Aviv Medical Center].

TNF alpha is a pro-inflammatory cytokine in Crohn's disease and it's neutralization is beneficial in patients with active disease. Remicade is a chimeric monoclonal anti-TNF antibody. Remicade is used in our center since December 1998 in 13 patients who were treated for active disease or fistula. We followed the patients and treatment results in order to estimate the efficacy and safety of this preparation. Response to treatment was measured by the Crohn's Disease Activity Index (CDAI) in patients treated due to active disease, or by the presence of discharge from external fistulae. Five out of seven patients with fistulae had less or no discharge after completing a course of 3 infusions. Four out of 6 patients treated due to active disease improved significantly after a single infusion. Five out of the six needed additional injections due to symptom recurrence. Intervals between infusions were 2 weeks--for fistulae patients to 32 weeks for patients with active disease. Adverse events for the 13 patients were usually mild except for 4 patients that suffered from anaphylactic shock, disseminated eruption (2) and eosinophilic pneumonitis. In summary, treatment of patients with active Crohn's disease or fistulae with monoclonal anti-TNF antibodies is an effective and relatively safe option after established treatment has failed. Analyzing the results of on going clinical trials and of the patients treated off-protocol will enable to establish new treatment strategies for patients with active Crohn's disease and fistulae.

Adolescent↗
PubMed2001

ICE--an efficient drug combination for stem cell mobilization and high-dose treatment of malignant lymphoma.

Between 1989 and 1999 we studied the ICE regimen in sequential trials in 290 patients with malignant lymphoma and germ-cell tumours. For patients with relapsed or refractory lymphoma we could demonstrate a comparable efficacy of ICE to other high-dose chemotherapy (HDCT) regimens but with a toxicity profile in favour of ICE. From a retrospective comparative analysis of ICE as HDCT regimen in patients with malignant lymphoma and germ-cell tumours we conclude that the characteristic toxicity profile of ICE varies depending on prior drug exposure of individual patients. Further dose intensification of ICE may be achieved with acceptable toxicity by adding further drugs (e.g. anthracyclines) or by treatment with sequential cycles of ICE (Tandem-HDCT). More convenient drug formulations (e.g. etoposide phosphate) might further improve the therapeutic index of ICE.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

[Gastrointestinal bleeding in children--etiology and diagnosis. Survey of patients in a Tel Aviv medical center, in the years 1990 to 1997].

During 1990-1997 we investigated 201 children with gastrointestinal bleeding. Average age was 3.9 +/- 6 years; 57.2% were males. There were 129 (64.2%) cases of lower and 72 (35.8%) of upper GI bleeding. Complications of upper GI bleeding were more severe than those of the lower: 6 of 8 (75%) patients who deteriorated into hypovolemic shock had upper GI bleeding; 40 of 50 (80%) who required i.v. fluids (crystaloids and/or blood) had also bled from the upper GI tract; but anemia was more frequent (27.7% vs 17%) in lower GI bleeding. The main etiology for upper GI bleeding was peptic ulcer, and for lower GI bleeding anal fissure. Mean hospital stay for upper GI bleeding was 3.87 +/- 2.61 days vs 3.40 +/- 3.51 for lower (not significant). In 34% the etiology of bleeding was undetermined. Although current literature refers to intussusception as a common cause of GI bleeding in infancy, we had no such cases. This difference might have resulted from our diagnoses being made earlier, before mucosal damage could have caused bleeding. We found polyps the second most frequent cause for lower GI bleeding in children. Endoscopy was of more benefit than any other diagnostic method, while barium enema and ultrasound had no diagnostic value. Stool culture did not contribute to diagnosis: only 3 of 36 were positive, so it is only necessary when there is bloody diarrhea.

Adolescent↗
PubMed2000

Passive smoking in patients with inflammatory bowel disease: an Israeli multicentre case-control study.

BACKGROUND: The association between smoking and inflammatory bowel disease (IBD) is well established. There are, however, no large scale studies of passive smoking in inflammatory bowel disease and this has never been surveyed in the Jewish population of Israel. AIM: To study the passive smoking exposure of Jewish IBD patients in Israel in a large scale multicentre study. METHODS: Patients with established IBD, aged 18-70 years, were interviewed regarding smoking and other habits. Two controls, one clinic and one neighbourhood, matched by age, sex, community group, and education, were sought for each subject. RESULTS: Five hundred and thirty-four patients (273 ulcerative colitis (UC) and 261 Crohn's disease (CD)), 478 clinic controls and 430 community controls were interviewed. There were no significant differences in the passive smoking habits between IBD patients and their controls. Fifty-one percent of UC patients, 50% of the clinic controls and 58% of the community controls were exposed to passive smoking at home (NS); similar results were found among CD patients (50%, 55% and 56%, respectively). When a quantitative exposure index was used UC patients were significantly less exposed to passive smoking than were their community controls (7.46 +/- 8.40 vs 9.36 +/- 9.46, n = 229, P< 0.031). There was no difference in the exposure to passive smoking among CD patients and their controls. No differences in exposure to passive smoking were found when UC patients who had never smoked were compared with their controls. When the quantitative index was used 'never-smoked' CD patients tended to be less exposed to passive smoking at home than their community controls (5.40 +/- 7.60 vs 8.04 +/- 8.72, P < 0.05). CONCLUSION: There is a lack of association between passive smoking and IBD in Jewish patients in Israel. When a quantitative exposure index was used UC patients were found to be less exposed to passive smoking than their community controls.

Adolescent↗
PubMed2000

Lack of association between smoking and Crohn's disease but the usual association with ulcerative colitis in Jewish patients in Israel: a multicenter study.

OBJECTIVE: The association between smoking and inflammatory bowel disease (IBD) is well established, but data in Jewish patients in Israel were discrepant. The aim of this study was to examine the smoking habits of Jewish IBD patients in Israel in a large scale, multicenter study. METHODS: Patients with established IBD aged 18-70 yr were interviewed in relation to smoking and other habits. Two controls (one clinic and one neighborhood control matched by age, sex, community group, and education) were sought for each subject. RESULTS: A total of 534 patients (273 ulcerative colitis [UC], and 261 Crohn's disease [CD]), along with 478 clinic controls and 430 neighborhood controls, were interviewed. There was no significant difference in the smoking habits between CD patients and their controls. Of patients with CD, 24.5% were current smokers, as compared to 19.9% of clinic controls and 25.2% of neighborhood controls (NS). The odds ratio for CD in current smokers was 1.30 (95% confidence interval 0.85-1.99) versus clinic controls, and 0.96 (0.63-1.46) versus neighborhood controls. There were also no significant differences in the proportion of ex-smokers between the groups. Only 12.9% of UC patients were current smokers versus 21.9. % Clinic controls, and 26.4% community controls (p<0.005). The proportions of ex-smokers were higher in UC patients 29.7% versus 25.9%, and 19.5% in their respective controls (p<0.001 vs. community controls). No significant differences were found in the proportions of never-smokers between IBD patients and controls. All the above trends were similar in four different parts of the country. The proportion of current smokers in UC decreased with the extent of disease (19.7% in proctitis, 13.6% in left-sided, and 4.5% in total colitis) (p<0.05). Patients with UC were more likely to be light smokers(1-10 cigarettes/day), whereas patients with CD were more likely to be moderate smokers (11-20 cigarettes/day) in comparison to their controls. CONCLUSIONS: The lack of association between smoking and CD has now been established in Jewish patients in Israel. The association was found in UC. The stronger genetic tendency in CD may contribute to this discrepancy.

Adolescent↗
PubMed2000

Comparison of assays for anti-endomysial and anti-transglutaminase antibodies for diagnosis of pediatric celiac disease.

BACKGROUND: Anti-endomysial antibodies are sensitive and specific markers for celiac disease. This antibody has recently been identified as an antibody to tissue transglutaminase, an enzyme that cross-links and stabilizes extracellular matrix proteins. OBJECTIVES: To evaluate the clinical usefulness of an enzyme-linked immunoassay for anti-transglutaminase antibodies, and to compare the results with those of AEA, the current gold standard serological test for celiac disease. METHODS: Serum samples were collected from 33 patients with biopsy-proven celiac disease and AEA tests were performed. Control samples for anti-transglutaminase were obtained from 155 patients. An ELISA test for immunoglobulin A anti-transglutaminase utilizing guinea pig liver transglutaminase was developed and performed on all sera. Cutoff values for the test were performed using logistic regression and receiver operating curves analysis. RESULTS: An optical density cutoff value of 0.34 was established for the assay. The mean value was 0.18 +/- 0.19 optical density for controls, and 1.65 +/- 1.14 for patients with celiac disease (P < 0.001). Sensitivity and specificity of the assay were both 90%, while AEA had a sensitivity and specificity of 100% and 94%, respectively. CONCLUSIONS: A tissue transglutaminase-based ELISA test is both sensitive and specific for detection of celiac disease.

Analysis of Variance↗
PubMed2000

Chronic hepatitis B virus in children in Israel: clinical and epidemiological characteristics and response to interferon therapy.

OBJECTIVE: To describe the clinical and epidemiological features of hepatitis B virus infection in Israeli children, and to evaluate their response and compliance to therapy. METHODS: We retrospectively studied 51 patients (34 males, 17 females), aged 2-18 years, from several medical centers in Israel. RESULTS: Of the 51 patients, 38 with elevated transaminase, positive hepatitis B e antigen and/or HBV DNA, and histologic evidence of liver inflammation were treated. Interferon was administered by subcutaneous injections three times a week for 3-12 months (dosage range 3-6 MU/m2). Only 16% were native Israelis, while 78% of the children were of USSR origin. A family history of HBV infection was recorded in 25 of the 51 patients (9 mothers, 16 fathers or siblings). Five children had a history of blood transfusion. The histological findings were normal in 3 patients, 24 had chronic persistent hepatitis, 14 had chronic active hepatitis and 2 had chronic lobular hepatitis. Five children also had anti-hepatitis D virus antibodies. Twelve of the 38 treated patients (31.5%) responded to IFN completely, with normalization of the transaminase levels and disappearance of HBeAg and HBV DNA. In no patient was there a loss of hepatitis B surface antigen. The main side effects of IFN were fever in 20 children, weakness in 10, headaches in 9, and anorexia in 6; nausea, abdominal pain, and leukopenia were present in 3 cases each. The response rate was not affected by age, country of origin, alanine/aspartate aminotransferase levels, or histological findings. However, a history of blood transfusion was a predictor of good response, 60% vs 27% (P < 0.05). CONCLUSIONS: We found IFN to be a safe and adequate mode of treatment in children with chronic HBV infection, regardless of their liver histology and transaminase levels. Therefore, in view of the transient side effects associated with this drug, we recommend considering its use in all children with chronic hepatitis B.

Adolescent↗
PubMed2000

First generation cephalosporins as therapy for uncomplicated pyelonephritis in children. A retrospective analysis.

There is no consensus opinion for the optimal management of pyelonephritis in children. We summarized our experience with first generation cephalosporins by a retrospective analysis of 129 pediatric patients with pyelonephritis who were treated either by first generation cephalosporins (97 patients, group 1) or broad-spectrum antibiotics (32 patients, group 2). Group 1 patients were less likely to have reported previous urinary infections or anatomical urinary tract abnormalities (16.2% vs. 53.1%, p= 0.002) and pathogens other than E. coli (7.3% vs. 25%, p=0.02). Resistance to first generation cephalosporins was identified in 22.6% of pathogens cultured, however, only 7.5% of them had poor clinical responses and required alternative treatment replacement. Our findings show that first generation cephalosporins could be used in our region to treat pyelonephritis in an otherwise healthy child, and that they can provide therapeutic success even in the face of apparent bacterial resistance.

Anti-Bacterial Agents↗
PubMed1999

Feasibility of multidimensional substance abuse treatment matching: automating the ASAM Patient Placement Criteria. American Society of Addiction Medicine.

UNLABELLED: The Patient Placement Criteria published by the American Society of Addiction Medicine (ASAM Criteria) established a non-proprietary standard for matching substance use disorder patients to treatment settings. METHODS: Data from 593 substance dependent adults who were assessed using the first computerized implementation of the ASAM Criteria were analyzed to determine whether the level of care assignments showed significant differences on a variety of clinical measures. RESULTS: The algorithm showed acceptable discrimination between each of three ASAM Levels of Care across numerous clinical subscales. CONCLUSIONS: It is feasible to implement complex, multidimensional criteria for substance abuse treatment that may improve reliability and facilitate validity studies.

Adolescent↗
PubMed1999

Evaluation of a new immunochromatographic test for Helicobacter pylori IgG antibodies in elderly symptomatic patients.

AIM: To determine the diagnostic value of a new serum and whole blood serological IgG antibody test, FlexPack HP, for the diagnosis of Helicobacter pylori in elderly symptomatic patients. METHODS: 94 consecutive symptomatic patients who underwent upper endoscopy were studied (mean age, 62.6 years). On endoscopy, the presence of H. pylori infection was examined by biopsies from gastric antrum and body for rapid urease test and histologic examination. Blood was drawn prior to endoscopy and both blood and serum were immediately analyzed for human IgG antibodies to H. pylori by a new commercially available qualitative immunochromatographic method, FlexPack HP. This test incorporates high-molecular weight cell-associated proteins (HM-CAP), which are highly specific for H. pylori IgG antibodies. RESULTS: Overall agreement for FlexPack HP whole blood vs FlexPack HP serum was 100%, and agreement with biopsy results was 71%. The gold standard (detection of H. pylori by histology or urease test) identified H. pylori in 61 patients (65%). Complete agreement was observed between the gold standard test and the serology kit in 72% (68/94) of sera (51 positive and 17 negative). Disagreement was found in sera of 26 patients; 16 sera were negative by the gold standard and positive by FlexPack HP and 10 patients were found negative by serology. The sensitivity of FlexPack HP was 84% and the specificity 52% when compared with the gold standard. CONCLUSIONS: FlexPack HP serum and whole blood test is a simple and reliable method for the detection of H. pylori antibodies, with 100% agreement between the serum and blood results. In the elderly symptomatic patients the sensitivity of FlexPack HP was similar to that of other serologic tests, but the specificity was relatively low, limiting its use in this population.

Aged↗
PubMed1999

The Ras antagonist, farnesylthiosalicylic acid (FTS), inhibits experimentally-induced liver cirrhosis in rats.

BACKGROUND/AIMS: Protooncogenes may play an important role, not only in carcinogenesis, but also in the regulation of normal cellular proliferation and differentiation. Several studies have indicated increased expression of the Ras protooncogenes in the liver in animal models and in patients with liver cirrhosis. The aim of the present study was to examine whether a synthetic Ras antagonist, S-farnesylthiosalicylic acid (FTS), which specifically dislodges Ras from the membrane of Ras-transformed fibroblasts (EJ cells), can prevent experimentally-induced liver cirrhosis in rats. METHODS: Cirrhosis was induced in male Wistar rats by intraperitoneal administration of thioacetamide (200 mg/kg twice weekly for 12 weeks). The Ras antagonist, farnesylthiosalicylic acid (FTS, 5 mg/kg), was administered during the study period 3 times a week. Ras expression in the liver was determined by Western blot analysis with pan anti-Ras antibodies and by immunohistochemistry. RESULTS: Rats treated with thioacetamide and the Ras antagonist, farnesylthiosalicylic acid (FTS), for 12 weeks had lower histopathologic scores of fibrosis and inflammation (p-values of 0.003 and 0.008, respectively) than those treated with thioacetamide only. There were no differences between the histopathologic scores in vehicle (control) and in Ras-antagonist (FTS) only treatments. Analysis of hepatic hydroxyproline levels from the two thioacetamide-treated groups and controls confirmed the histopathologic scores (7.7+/-0.9 mg/g protein in the TAA-treated vs. 3.8+/-0.5 mg/g protein in the TAA+FTS treated group, p = 0.007). Ras levels, determined by Western blot analysis, were markedly increased in the livers treated with TAA (17-fold over control) and significantly decreased (by about 70%) in the livers of rats treated with TAA and FTS. Studies in isolated human hepatic stellate cells demonstrated that FTS inhibited both DNA synthesis and migration of those cells (p<0.05). CONCLUSION: These results indicate that inhibition of Ras expression in the liver during fibrogenesis, prevents the development of experimentally-induced hepatic cirrhosis.

Animals↗