Population pharmacokinetics of etoposide.
Explore the source record for details and available documents.
Antineoplastic Agents, Alkylating↗
Biomedical subjects
S Reif
Publications and source records attributed to S Reif.
Population pharmacokinetics of cyclophosphamide, doxorubicin and etoposide in 30 patients with BEACOPP chemotherapy.
Explore the source record for details and available documents.
Adolescent↗
Feasibility of intraventricular administration of etoposide in patients with metastatic brain tumours.
As the systemic administration of etoposide is effective in the treatment of relapsed and metastatic brain tumours, a pilot trial was designed to study the feasibility of intraventricular administration of etoposide in such patients. 14 patients aged 2.1 to 33.2 years were treated with intraventricular etoposide simultaneously with either oral or intravenous chemotherapy with trofosfamide or carboplatin and etoposide. In 59 courses (1-12/patient) 0.5 mg etoposide was administered daily via an indwelling subcutaneous reservoir for 5 consecutive days every 2-5 weeks over a period of 0-11 months. During 15 courses in 5 patients serial CSF samples were obtained and etoposide levels were determined by reversed-phase HPLC. Side effects included transient headache and bacterial meningitis, each during 2 courses. Pharmacokinetic data analysis in the CSF (11 courses, 4 patients) revealed a terminal half-life of 7.4+/-1.2 hours and an AUC of 25.0 +/- 9.5 microg h ml(-1)(mean +/- standard deviation). The volume of distribution at steady state and total clearance exhibited a large interindividual variability with mean values of 0.16 l and 0.46 ml min(-1)respectively. Intraventricularly administered etoposide is well tolerated. CSF peak levels exceed more than 100-fold those achieved with intravenous infusions. Further studies should be focused on optimizing the dose and schedule and on determining the effectiveness of intraventricularly administered etoposide.
Adolescent↗
Intramitochondrial dimerization of citrate synthase characterized by blue native electrophoresis.
Explore the source record for details and available documents.
Citrate (si)-Synthase↗
Organizational and financial issues in the delivery of substance abuse treatment services.
Examination of organizational and financial characteristics of the specialty substance abuse treatment system allows an understanding of how to meet the needs of clients in the system. Further, this assessment may afford insights into how the specialty sector may adapt in the changing environment of managed care. Data from Phase I of the Alcohol and Drug Services Study (ADSS) describe the specialty substance abuse treatment system in terms of type of care, setting, level of affiliation, licensure/accreditation, ownership, revenue sources, client referral sources, client's primary substance of abuse, and managed care. Although the system is largely outpatient and remains substantially two tiered in terms of public/private funding mix, it varies along a number of organizational and financial dimensions which have implications for system structure and facility viability in the changing environment of substance abuse treatment service delivery.
Alcoholism↗
Access to services in the substance abuse treatment system. Variations by facility characteristics.
In view of the importance of type and intensity of services during substance abuse treatment, this chapter looks at treatment and support services that substance abuse clients have access to during treatment. Trends in services over recent years are described. Services available to clients in the current treatment system are reviewed. Several facility characteristics affecting access to services are examined. Different ways of defining access to services are discussed. Findings from the Alcohol and Drug Services Study are used to illustrate service patterns in the national substance abuse treatment system. Variations in service patterns by facility characteristics such as type of care, treatment setting, ownership, percent of facility dependence on public revenue, and level of affiliation are analyzed. The implication is that clients who enter into treatment at different types of facilities are likely to have access to certain types of services.
Combined Modality Therapy↗
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↗
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↗
Granulomatosis cheilitis and Crohn disease.
Explore the source record for details and available documents.
Adolescent↗
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↗
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↗
[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↗
[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↗
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↗
[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↗
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↗
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↗
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↗