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Biomedical subjects

J Otten

Publications and source records attributed to J Otten.

At least 19 recordsLinked to original sources

Hospital outbreak of multidrug-resistant Mycobacterium tuberculosis infections. Factors in transmission to staff and HIV-infected patients.

OBJECTIVE: To describe transmission of multidrug-resistant (MDR) Mycobacterium tuberculosis infection among patients and health care workers (HCWs) in a ward and clinic for human immunodeficiency virus (HIV)-infected patients in a hospital, four studies were conducted. METHODS: Case patients and control patients were persons who had been treated in the HIV ward or clinic, whose clinical course was consistent with tuberculosis and who had at least one positive culture for M tuberculosis between January 1, 1988, and January 31, 1990, resistant to at least isoniazid and rifampin (case patients), or whose isolates were susceptible to all drugs tested (control patients). In the first study, case patients and control patients were compared to identify risk factors for MDR tuberculosis. In the second study, inpatient and outpatient days of MDR tuberculosis case patients were compared to determine whether acid-fast bacillus (AFB) smear-positivity or aerosolized pentamidine use was associated with higher numbers of subsequent MDR tuberculosis cases among exposed patients. In the third study, restriction fragment length polymorphism analysis was performed on available MDR and sensitive M tuberculosis isolates. In the fourth study, skin test conversion rates among HCWs in the HIV ward and clinic were compared with those of HCWs in another ward, and the strength of the associations between skin test conversions among HCWs on the HIV ward and the number of person-days that AFB smear-positive case patients and control patients were on this ward was estimated. RESULTS: Case patients were more likely than control patients to have been exposed on the HIV ward or clinic to an AFB smear-positive case patient (P less than .001). Inpatient and outpatient days of MDR tuberculosis case patients were associated with more subsequent cases of MDR tuberculosis if exposing case patients were smear-positive or if they received aerosolized pentamidine (P less than or equal to .01). Of 13 MDR isolates, all had one of two restriction fragment length polymorphism patterns; 10 sensitive isolates had restriction fragment length polymorphism patterns that were different from each other. The HCW skin test conversion rate was higher on the HIV ward and clinic than on the comparison ward (P less than .01). The risk of occupational acquisition of infection increased in direct proportion to the number of person-days that AFB smear-positive case patients were on the HIV ward (r = .75; P = .005), but did not increase in proportion to the number of person-days that AFB smear-positive control patients were there (r = -.36; P = NS). After isolation measures for AFB smear-positive tuberculosis patients were improved, MDR tuberculosis cases decreased to seven of 214 tuberculosis patients. CONCLUSIONS: Nosocomial transmission of MDR M tuberculosis infection to patients and HCWs occurred on the HIV ward and clinic. Infectiousness of MDR tuberculosis case patients was associated with AFB sputum-smear positivity. Case patients with MDR tuberculosis created a greater risk of skin test conversion for HCWs on the HIV ward than drug-susceptible control patients.

Adult

Thyroid function during L-asparaginase therapy in children with acute lymphoblastic leukemia: difference between induction and late intensification.

Parameters of thyroid function were measured in nine children during induction therapy for acute lymphoblastic leukemia (ALL). Seven patients were reevaluated during the late intensification phase. Vincristine, anthracycline drugs (daunorubicin and adriamycin), corticosteroids, and L-asparaginase were used in the two phases of therapy. During induction, L-asparaginase (5,000 U/m2) was given daily on days 1-21. During late intensification, the drug was given on days 1, 4, 8, and 11 (10,000 U/m2). During induction, total T4 significantly decreased from 10.1 +/- 2.3 to 4.0 +/- 1.0 micrograms/dl, FT4 decreased from 1.4 +/- 0.3 to 0.7 +/- 0.2 ng/dl, total T3 decreased from 134 +/- 32 to 57 +/- 21 ng/dl, and thyroxine binding globulin (TBG) decreased from 2.1 +/- 0.6 to 0.8 +/- 0.3 mg/dl. During late intensification therapy, significant decreases in T3 (from 180 +/- 26 to 93 +/- 40 ng/dl) and TBG (from 1.9 +/- 0.5 to 1.1 +/- 0.5 mg/dl) were observed, but there were no significant changes in T4 and FT4. We conclude that during induction, the impairment of thyroid function is attributable to L-asparaginase, whereas during late intensification, low T3 and low TBG is due to glucocorticoid administration.

Adolescent

[Medulloblastoma: analysis of 14 cases treated at the J. Bordet Institute and literature review].

Between 1966 and 1986, 14 patients with histologically verified cerebellar medulloblastomas were seen at J. Bordet Institute after total (4 cases) or partial (10 cases) tumor removal. Twelve received postoperative irradiation after some courses of chemotherapy (Vincristine, Procarbazine, Methotrexate) for 5. In 10 cases the X ray treatment was given to the whole cerebrospinal axis with approximately 50 Gy delivered to the primary tumor site, 25-35 Gy to the remaining brain and spinal cord. As in other series of the literature the long term prognosis is not too good, with approximately 50% of the patients surviving more than 5 years. Failure at the primary site happened in 4 cases. As a consequence of the small number of patients treated, no conclusion can be drawn from risk factor analysis. Yet it appears that younger patients fared better than older ones. A detailed description of the side effects of the treatment is therefore given for the five children treated at prepubertal age: some growth impairment seems to be the rule, a consequence of GH deficiency--if not compensated--and of the direct effect of ionizing radiation on the vertebral bodies. While discussing the progress of neurosurgery and radiotherapy for the treatment of medulloblastoma, the authors emphasize the need of more efficient adjuvant chemotherapy regimens and the interest of multicenter trial for evaluating them.

Adolescent

Ifosfamide-induced Fanconi's syndrome with growth failure in a 2-year-old child.

Fanconi's syndrome with phosphopenic rickets is described in a 2-year-old girl who had been treated for an embryonal sarcoma with multiagent chemotherapy including high-dose ifosfamide. The radiological and biochemical signs of rickets disappeared after treatment with 25-OH vitamin D3 and phosphorus supplements. Monitoring of tubular function in children during and after treatment with ifosfamide is mandatory.

Child, Preschool

High survival rate in advanced-stage B-cell lymphomas and leukemias without CNS involvement with a short intensive polychemotherapy: results from the French Pediatric Oncology Society of a randomized trial of 216 children.

From April 1984 to December 1987, the French Pediatric Oncology Society (SFOP) organized a randomized trial for advanced-stage B-cell lymphoma without CNS involvement to study the possibility of reducing the length of treatment to 4 months. After receiving the same three intensive six-drug induction courses based on high-dose fractionated cyclophosphamide, high-dose methotrexate (HD MTX), and cytarabine in continuous infusion, patients were evaluated for remission. Those who achieved complete remission (CR) were randomized between a long arm (five additional courses with two additional drugs; 16 weeks of treatment) and a short arm (two additional courses; 5 weeks). For patients in partial remission (PR), intensification of treatment was indicated. Two hundred sixteen patients were registered: 15 stage II nasopharyngeal and extensive facial tumors, 167 stage III, and 34 stage IV, 20 of the latter having more than 25% blast cells in bone marrow. The primary sites of involvement were abdomen in 172, head and neck in 30, thorax in two, and other sites in 12. One hundred sixty-seven patients are alive in first CR with a minimum follow-up of 18 months; four are lost to follow-up. Eight patients died from initial treatment failure, 14 died from toxicity or deaths unrelated to tumor or treatment, and 27 relapsed. The event-free survival (EFS), with a median follow-up of 38 months, is 78% (SE 3) for all the patients, 73% (SE 11) for the stage II patients, 80% (SE 3) for the stage III patients, and 68% (SE 8) for the stage IV and acute lymphoblastic leukemia (ALL) patients. One hundred sixty-six patients were randomized: 82 in the short arm and 84 in the long arm. EFS is, respectively, 89% and 87%. Statistical analysis confirms equivalence of both treatment arms with regard to EFS. Moreover, morbidity was lower in the short arm. This study confirms the high survival rate obtained in the previous LMB 0281 study without radiotherapy or debulking surgery and demonstrates the effectiveness of short treatment.

Adolescent

Consolidating the role of *I-MIBG-scintigraphy in childhood neuroblastoma: five years of clinical experience.

In recent years, *I-MIBG (*I-metaiodobenzylguanidine), which is transported and stored in the chromaffin cells, has been shown to allow good visualization of neuroblastomas in children. This paper deals with 30 *I-MIBG-scans performed in 20 children: 16 with neuroblastoma, 3 with retinoblastoma, and 1 with a malignant paraganglioma. A high detection rate was found for both primary and secondary sites of neuroblastoma. *I-MIBG was generally superior to 99mTc-MDP bone scintigraphy in the detection of bone metastases. Our experience illustrates the unique place of *I-MIBG-scintigraphy compared with other imaging techniques: it makes it possible to define the nature of the tumour, particularly in cases with normal catecholamine levels; to establish how extensive the lesions are at the time of diagnosis; and to confirm complete remission. No abnormal *I-MIBG uptake was noted in the 3 cases of retinoblastoma.

3-Iodobenzylguanidine

CSF drug levels for children with acute lymphoblastic leukemia treated by 5 g/m2 methotrexate. A study from the EORTC Children's Leukemia Cooperative Group.

A multicenter EORTC study was conducted in children with acute lymphocytic leukemia to determine whether 5 g/m2 of methotrexate (MTX) (24 h i.v. infusion, four cycles) is an appropriate dosage for obtaining CSF drug concentrations approaching the critical cytotoxic level of 10(-6) M. A total of 193 cycles were analyzed for 58 patients. At the end of the 24 h infusion, the mean MTX serum level was 65.27 +/- 33.11 microM; the mean CSF MTX level was 1.47 +/- 1.1 microM; no significant difference in CSF MTX levels was observed between patients with (n = 20) and those without i.v. Ara-C (n = 38). The mean CSF MTX/serum MTX ratio was 0.029 +/- 0.027. CSF drug concentrations greater than or equal to 10(-6) M were achieved in 81% of the courses. The highest level was 8.4 X 10(-6) M. Only 5% of patients failed to achieve this drug concentration in at least one cycle. No significant correlation was observed between blood and CSF MTX levels. Mean CSF MTX levels were comparable from one cycle to another.

Adolescent

Immunomagnetic purging of bone marrow grafts for autologous transplantation in neuroblastoma.

Bone marrow grafts of 5 patients with stage IV neuroblastoma and one patient with stage IV retinoblastoma were harvested during complete remission and in vitro processed for autologous transplantation. Because of the risk to reinfuse metastatic cells, the grafts were immunomagnetically purged. After preparation of the buffy coat fraction, mononuclear cells (mnc) and progenitor cells (CFU-GM) were enriched by density centrifugation and incubated successively with a cocktail of five tumour reacting monoclonal antibodies and magnetic microparticles. Target cells were removed by a set of samarium cobalt magnets. The purged grafts were stored in liquid nitrogen. After the complete procedure, an average of 16% nucleated cells of the initial harvest could be recovered. This corresponds with a mean number of 0.5 X 10(8) mnc and 2.4 X 10(4) CFU-GM per kg body weight being available for grafting. So far, 5 patients received their purged marrow graft and showed a sustained take.

Bone Marrow Cells

[I-MIBG scintigraphy in the diagnosis of neuroblastoma in children].

Since the early eighties, *I-MIBG (= *I-metaiodobenzylguanidine), which is stored in the neurotransmitter storage granules of chromaffin cells, has been increasingly used for the detection of pheochromocytomas and allied sympathoadrenal pathologies. The aim of this paper is to illustrate, by means of clinical examples, the role of *I-MIBG-scintigraphy in child neuroblastoma and to underline its original place, compared with other imaging techniques, in determining the neuro-ectodermal origin of a tumor as well as in establishing the extension of the lesions at the time of diagnosis and during follow-up.

3-Iodobenzylguanidine

Alkane utilization in Pseudomonas oleovorans. Structure and function of the regulatory locus alkR.

The OCT plasmid-localized alkBAC operon encodes enzymes for alkane hydroxylation and alkanol dehydrogenation. The positively controlled expression of the operon is very efficient in both Pseudomonas putida and Escherichia coli. Two regulatory functions have been ascribed to the regulatory locus alkR: inducer recognition and transcriptional activation of the operon. We have cloned and localized the alkR locus on a 4.9-kilobase pair SalI fragment. The alkR region was analyzed for translation productions in E. coli minicells. Two proteins were identified: a 99- and a 48-kDa peptide. The positions of the cistrons encoding these proteins were established. Both cistrons were shown to be essential for an Alk phenotype. The first cistron (alkS), which encodes the 99-kDa protein, complemented alkR mutations affecting inducer specificity. Furthermore, we found that alkS is responsible for activation of expression of the alkBAC operon since it is required for the induction of the alkB gene product alkane hydroxylase. The second cistron (alkT), which encodes the 48-kDa protein, is required for reconstitution of an Alk phenotype but has no function in regulation of alkBAC expression. Thus, the expression of the alkBAC operon is regulated by a 99-kDa protein, whereas the 48-kDa protein is probably a component of the alkane hydroxylase complex.

Bacterial Proteins

Prognostic factors in 281 children with nonmetastatic rhabdomyosarcoma (RMS) at diagnosis.

Pretreatment characteristics of 281 children with nonmetastatic rhabdomyosarcoma, included in the registry of the International Society of Pediatric Oncology (SIOP) between January 1975 and December 1983, were examined to study the children's prognosis. The multivariate statistical method (Cox regression model) was used for each of two endpoints: survival time and disease-free time. The three most important predictors for survival time were primary site (p less than .001), clinical stage (p = .009), and sex (p = .020). The best results involved paratesticular and orbital primary sites, regardless of the clinical stage; males fared slightly better than females. These same three factors were also significant predictors for disease-free time.

Adolescent

Neuroblastoma today.

Notwithstanding the progress made in radiology, nuclear medicine, immunohematology and genetics for more accurate diagnosis and staging in neuroblastoma and the availability of general new efficacious cytostatic drugs, the prognosis of children over 1 yr with advanced disease has remained poor. New refinements in therapeutics with multiagent regimens, massive chemotherapy followed by autologous bone marrow transplantation treatment, with or without immunomagnetic purging, and/or total body irradiation have improved response rate and disease-free survival in metastatic patients, but their effect on long-term survival needs further evaluation.

3-Iodobenzylguanidine