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Biomedical subjects

R Nitschke

Publications and source records attributed to R Nitschke.

At least 127 records · Page 7Linked to original sources
PubMed1975

Intensive chemotherapy as primary treatment for rhabdomyosarcoma of the pelvis.

Twenty-six cases of childhood rhabdomyosarcoma involving the pelvis were treated at Childrens Hospital of Los Angeles between 1950 and 1972. The median survival of 17 patients treated up to 1970 was 6 months. Of a group of 9 patients treated with intensive chemotherapy (ICG) prior to surgery and/or x-ray therapy, 5 are surviving from 12 to 60 months and have a relative survival rate of 4.5 times that of the mixed therapy group (MTG) (p = 0.01). Deaths have occurred only in patients with Stage IV disease. The use of preoperative chemotherapy with or without x-ray therapy followed by local surgical excision when necessary can be as effective in prolonging the survival of children with pelvic rhabdomyosarcoma as those obtained with more traditional approaches; this limitation in use of surgery is likely to preserve the quality of life, should the child live to adulthood.

Adolescent↗
PubMed1975

Inhibitory effects of mitogens on adenoidal lymphocytes in vitro.

Cultures of human adenoidal lymphocytes exposed briefly to either phytohemagglutinin (PHA), Staphylococcus filtrate (Staph-F), concanavalin-A (Con-A), or pokeweed mitogen (PWM) incorporate increased amounts of thymidine earlier than replicate cultures exposed continuously to the mitogens. These effects can begin in the first 24 hr of culture and are seen maximally between 36 and 72 hr. Once a blastogenic response is established, PHA or PWM can diminish that response. Inhibition with PWM requires that the initial stimulation was with this mitogen, while PHA can inhibit blastogenesis to both PHA and PWM-stimulated cells. Because these mitogens can have a paradoxical effect on adenoidal lymphocytes, being capable of both initiating and inhibiting DNA synthesis, this phenomena should be kept in mind when such systems are utilized for the evaluation of antigens and drug effects.

Adenoids↗
PubMedDate not supplied

Toxicity study of cytosine arabinoside and methotrexate in the maintenance therapy of childhood leukemia. A Southwest Oncology Group study.

In a toxicity study to determine the feasibility of treating patients with acute lymphocytic leukemia (ALL) using an intravenous combination of cytosine arabinoside (Ara-C) and methotrexate (MTX), the drugs were given either simultaneously or sequentially every two weeks. Twenty-nine patients were studied, 17 treated simultaneously, 12 treated sequentially. The tolerated doses of Ara-C and MTX were 60 mg/m2 and 90 mg/m2, respectively, for the simultaneous treatment schedule and 90 mg/m2 and 150 mg/m2, respectively, for the sequential treatment schedule. The dose-limiting factor of the drug combination was gastrointestinal toxicity. The observed recurrent vomiting on both schedules rendered the treatment unsuitable for maintenance therapy.

Adolescent↗
PubMedDate not supplied

The effect of intracellular pH on cytosolic Ca2+ in HT29 cells.

The influence of intracellular pH (pHi) on intracellular Ca2+ activity ([Ca2+]i) in HT29 cells was examined microspectrofluorometrically. pHi was changed by replacing phosphate buffer by the diffusible buffers CO2/HCO3- or NH3/NH4+ (pH 7.4). CO2/HCO3- buffers at 2,5 or 10% acidified pHi by 0.1, 0.32 and 0.38 pH units, respectively, and increased [Ca2+]i by 8-15 nmol/l. This effect was independent of the extracellular Ca2+ activity and the filling state of thapsigargin-sensitive Ca2+ stores. Removing the CO2/HCO3- buffer alkalinized pHi by 0.14 (2%), 0.27 (5%), and 0.38 (10%) units and enhanced [Ca2+]i to a peak value of 20, 65, and 143 nmol/l, respectively. Experiments carried out with Ca2+-free solution and with thapsigargin showed that the [Ca2+]i transient was due to release from intracellular pools and stimulated Ca2+ entry. NH3/NH4+ (20 mmol/l) induced a transient intracellular alkalinization by 0.6 pHunits and increased [Ca2+]i to a peak (Delta [Ca2+]i = 164 nmol/l). The peak [Ca2+]i increase was not influenced by removal of external Ca2+, but the decline to basal [Ca2+]i was faster. Neither the phospholipase C inhibitor U73122 nor the inositol 1,4,5-trisphosphate (InsP3) antagonist theophylline had any influence on the NH3/NH4+-stimulated [Ca2+]i increase, whereas carbachol-induced [Ca2+]i transients were reduced by more than 80% and 30%, respectively. InsP3 measurements showed no change of InsP3 during exposure to NH3/NH4+, whereas carbachol enhanced the InsP3 concentration, and this effect was abolished by U73122. The pHi influence on "capacitative" Ca2+ influx was also examined. An acid pHi attenuated, and an alkaline pHi enhanced, carbachol- and thapsigargin-induced [Ca2+]i influx. We conclude that: (1) an alkaline pHi releases Ca2+ from InsP3-dependent intracellular stores; (2) the store release is InsP3 independent and occurs via an as yet unknown mechanism; (3) the store release stimulates capacitative Ca2+ influx; (4) the capacitative Ca2+ influx activated by InsP3 agonists is decreased by acidic and enhanced by alkaline pHi. The effects of pHi on [Ca2+]i should be of relevance under many physiological conditions.

Ammonia↗
PubMedDate not supplied

Chemotherapy for patients with recurrent or refractory neuroblastoma: a POG Phase II study.

PURPOSE: The purpose of this study was to evaluate the efficacy and toxicity of three different salvage regimens (Rx) in children with recurrent or refractory neuroblastoma. PATIENTS AND METHODS: Forty-six children with recurrent or refractory neuroblastoma received treatment according to one of three regimens: Rx 1 (five patients), high-dose cisplatin (HDP) (200 mg/m2) with concurrent sodium thiosulfate (STS) (9.9 g/m2) as a nephroprotectant and etoposide (VP-16) (200 mg/m2/day for 3 days); Rx 2 (22 patients), high-dose carboplatin (HD-CBDCA) (500 mg/m2/day for 2 days) and VP-16 (100 mg/m2/day for 3 days); Rx 3 (19 patients), ifosfamide (1.5 g/m2/day for 3 days) followed by CBDCA (400 mg/m2) on day 4. Chemotherapy was administered every 3-4 weeks. Responses were assessed following four courses with or without surgery. Patients achieving less than a partial response (PR) on their primary treatment were crossed over to the next regimen (i.e., Rx 1 --> Rx 2 <--> Rx 3). RESULTS: Rx 1 was ended early owing to grade 4 nephrotoxicity in two patients following their first course. Ten of 22 evaluated patients (45%) primarily (n = 19) or secondarily (n = 3) treated by Rx 2 responded [five complete response (CR) and five PRs]. Nine of the 23 evaluated patients (39%) on Rx 3 as primary (n = 18) or secondary (n = 5) treatment responded (one CR and eight PRs). Grades 3-4 neutropenia and thrombocytopenia occurred after 80% and 50% of courses administered on Rx 2 and Rx 3, respectively. Central venous line infections were the most commonly documented infections on these regimens. CONCLUSIONS: Rx 2 and Rx 3 are active combinations in patients with recurrent or refractory neuroblastoma and are associated with manageable toxicity. HDP administered as a short i.v. infusion with concurrent STS infusion cannot be safely given to children with neuroblastoma pretreated with cisplatin.

Adolescent↗
PubMedDate not supplied

Topotecan in pediatric patients with recurrent and progressive solid tumors: a Pediatric Oncology Group phase II study.

PURPOSE: A phase II study was designed to determine the efficacy of topotecan, an inhibitor of topoisomerase I, in the treatment of patients with progressive or recurrent pediatric extracranial solid tumors (STs). PATIENTS AND METHODS: Patients younger than 21 years at the time of initial diagnosis with refractory STs were treated with 2 mg/m2 topotecan given by 30-minute infusions for 5 days repeated every 3 weeks. Granulocyte colony stimulating factor (G-CSF) was added to the regimen only after occurrence of severe neutropenia or therapy delay due to sustained neutropenia. RESULTS: One hundred forty-one patients were treated with 539 courses of topotecan. Responses were seen in 34 patients (3 had complete responses [CRs], 2 had partial responses [PRs], and 24 had minor responses [MRs] or stable disease [SD]). The number of administered courses in patients with SD varied between 5 and 24, with a median of 10. The median time on the study for patients with SD was approximately 8.5 months. In patients without bone marrow involvement, the most frequent toxicity was myelosuppression: hemoglobin < 8 g/dl in 83 of 341 courses, absolute granulocyte count < 1,000/microl in 221 of 341 courses, and platelet count < 50,000/microl in 162 of 341 courses. Nausea and vomiting were infrequent; many patients were pretreated with ondansetron or granisetron. A recurrent rash developed in 16 patients and was usually well controlled with diphenhydramine and hydrocortisone. G-CSF was administered in 203 of 539 courses because of neutropenia. Therapy was delayed over 1 week in 33 instances. CONCLUSION: In previously treated patients, topotecan produced CRs and PRs in patients with neuroblastoma, Ewing's tumor, and retinoblastoma. In hepatoblastoma, rhabdomyosarcoma, and a few rare tumors, long-lasting MRs and SDs with excellent symptom control were seen. The toxicity of topotecan, predominantly myelosuppression, was tolerable.

Adolescent↗
PubMedDate not supplied

Defects in processing and trafficking of cystic fibrosis transmembrane conductance regulator.

In most epithelial tissues Cl(-) transport relies on the cystic fibrosis transmembrane conductance regulator (CFTR) which has dual function as a Cl(-) channel and as a regulator of other ion channels. More than 900 different mutations in the CFTR gene are the cause for defective transport of Cl(-) and Na(+) and impaired secretion or absorption of electrolytes in cystic fibrosis. However, the CFTR mutation delta F508 is the most common reason for the frequently inherited disease among the Caucasian population. Maturation and processing of delta F508-CFTR is defective which leads to expression of only very little but functional CFTR in the cell membrane. Understanding the processing and trafficking of CFTR may give a clue to the question as to how the expression and residual function of delta F508-CFTR can be enhanced, and may lead to the development of new pharmacological tools for the treatment of cystic fibrosis.

Animals↗
PubMedDate not supplied

Evaluation of cis-dichlorodiammineplatinum(II) in children with advanced malignant diseases: Southwest Oncology Group Studies.

Two schedules of cis-dichlorodiammineplatinum(II) (cis-platinum) were evaluated for therapeutic efficacy and toxicity in children with malignant diseases resistant to standard therapy. Initially, cis-platinum was given as a rapid iv bolus injection at a dose of 15 mg/m2/day for 5 days every 3 weeks. The second schedule of cis-platinum was a dose of 1 mg/kg/week administered as an 8-hour infusion with mannitol. furosemide, and hydrating fluids. Using the daily schedule, no responses were seen among 23 children with acute lymphatic leukemia and only eight responses were noted among 47 children with solid tumors. Using the weekly schedule, three responses were noted among 25 children with solid tumors. Responses were observed in seven children with neuroblastoma, two with osteosarcoma, one with embryonal testicular carcinoma, and one with an endodermal sinus tumor. With one exception (a 4-year-old child with neuroblastoma), all responses were of short duration. The most common side effects with both schedules were nausea and vomiting which were usually controlled with antiemetics. The dose-limiting toxicity, especially on the 5-day schedule; was renal function impairment. Only one child who received cis-platinum weekly as an 8-hour infusion with diuresis had elevation of the serum creatinine level. Protocols are being initiated to determine the therapeutic effectiveness and toxicity of combination therapy with cis-platinum in children with neuroblastoma and osteosarcoma.

Bone Marrow↗
PubMedDate not supplied

Doxorubicin and cisplatin therapy in children with neuroblastoma resistant to conventional therapy: a Southwest Oncology Group Study.

Fifteen children with metastatic neuroblastoma resistant to vincristine and cyclophosphamide were treated with two drugs which were known to be effective as single drugs against neuroblastoma. The drugs were given in courses every 3 weeks. Doxorubicin (50 mg/m2 iv) was given on Day 1 and cisplatin (50 mg/m2) was administered on Day 2 as an 8-hour infusion, using a forced diuretic-hydration program. Three of the 15 children achieved partial or complete remission. Three children showed improvement. The other children either did not respond to the therapy or had progressive disease. The combination of doxorubicin and cisplatin given in the sequence outlined is no more effective than either drug given singly. The side effects of the drug combination were tolerable and were in keeping with previously described toxicity.

Child↗