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Biomedical subjects

R Nitschke

Publications and source records attributed to R Nitschke.

At least 91 records · Page 5Linked to original sources
PubMed1988

Differential effects of ADH on sodium, chloride, potassium, calcium and magnesium transport in cortical and medullary thick ascending limbs of mouse nephron.

The effect of antidiuretic hormone (arginine vasopressin, AVP) on transepithelial Na+, Cl-, K+, Ca2+ and Mg2+ net transports was investigated in medullary (mTAL) and cortical (cTAL) segments of the thick ascending limb (TAL) of mouse nephron, perfused in vitro. Transepithelial net fluxes (JNa+, JCl-, JK+, JCa2+, JMg2+) were determined by electron probe analysis of the collected tubular fluid. Transepithelial potential difference (PDte) and transepithelial resistance (Rte) were measured simultaneously. cTAL segments were bathed and perfused with isoosmolal, HCO3- containing Ringer solutions, mTAL segments were bathed and perfused with isoosmolal HCO3- free Ringer solutions. In cTAL segments, AVP (10(-10) mol.l-1) significantly increased JMg2+ and JCa2+ from 0.39 +/- 0.08 to 0.58 +/- 0.10 and from 0.86 +/- 0.13 to 1.19 +/- 0.15 pmol.min-1 mm-1 respectively. Neither JNa+ nor JCl-, (JNa+: 213 +/- 30 versus 221 +/- 28 pmol.min-1 mm-1, JCl-: 206 +/- 30 versus 220 +/- 23 pmol.min-1 mm-1) nor PDte (13.4 +/- 1.3 mV versus 14.1 +/- 1.9 mV) or Rte (24.6 +/- 6.5 omega cm2 versus 22.6 +/- 6.4 omega cm2) were significantly changed by AVP. No significant effect of AVP on net K+ transport was observed. In mTAL segments, Mg2+ and Ca2+ net transports were close to zero and AVP (10(-10) mol.l-1) elicited no effect. However NaCl net reabsorption was significantly stimulated by the hormone, JNa+ increased from 107 +/- 33 to 148 +/- 30 and JCl- from 121 +/- 33 to 165 +/- 32 pmol.min-1 mm-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Localized neuroblastoma treated by surgery: a Pediatric Oncology Group Study.

A prospective study was designed to evaluate the outcome of patients with localized resectable neuroblastoma without regional lymph node involvement when no therapy beyond surgical resection was administered. One hundred one patients observed for 3 to 60 months had a 2-year disease-free survival of 89% (SE = 5%). Of the nine patients experiencing relapse, only three have died. There were no apparent distinguishing characteristics of the nine failures. Due to the favorable prognosis of the subset of neuroblastoma patients, prognostic factor analysis had very limited power and lacked clinical importance. Complete gross removal of the localized tumors is adequate therapy to ensure the survival of the majority of these patients.

Child↗
PubMed1987

Molecular weight determination of the two segments of double-stranded RNA of infectious bursal disease virus, a member of the birnavirus group.

The molecular weights (mol. wts.) of the two double-stranded (ds) RNA segments of infectious bursal disease virus (IBDV) were determined using previously sequenced reovirus genes M3 and S2 as internal ds RNA reference molecules. Electrophoresis under fully denaturing conditions revealed mol. wts. of 2.26 X 10(6) daltons and 1.98 X 10(6) daltons. By direct length measurements under the electron microscope, using two different spreading conditions, the two segments were calculated to be composed of 3274 +/- 79 base pairs (bp) and 2821 +/- 59 bp or 3299 +/- 68 bp and 2830 +/- 73 bp, resulting in mol. wts. of 2.24-2.26 X 10(6) daltons and 1.93-1.94 X 10(6) daltons, respectively. Base pair distances of 2.67 +/- 0.08 A and 2.71 +/- 0.11 A in ds RNA were close to those of the A-RNA form; in ds DNA included as a control, the rise per base pair was 3.18 A, which is consistent with published results. Mol. wts. obtained for IBDV indicate that the RNAs of the other birnaviruses are also smaller than reported.

Animals↗
PubMed1987

The two segments of the infectious bursal disease virus genome are circularized by a 90,000-Da protein.

The genome of infectious bursal disease virus (IBDV) consists of two segments of double-stranded (ds)RNA with molecular weights of 2.2 X 10(6) and 1.9 X 10(6) Da, respectively. After treatment of IBDV particles with proteinase K in the presence of sodium dodecyl sulfate (SDS), linear dsRNA molecules are released from the virus particles. However, after heating of virus particles at 100 degrees for 3 min in 1.5% SDS, without the protease, dsRNA-protein complexes can be seen under the electron microscope: Knob-like proteinaceous structures are linked to the ends of the dsRNA molecules of either size class which are circularized to form individual rings. A 90,000-Da IBDV structural polypeptide, the only protein encoded by the smaller genome segment, has been demonstrated to remain firmly linked to the IBDV genome under these conditions. No functional data exist about this circularizing protein; it is a probable candidate for an RNA-dependent RNA polymerase or an assembly protein for the two dsRNA segments. At high particle concentrations, or when the preparations are allowed to stand for several hours before spreading, these complexes tend to aggregate to form flower-like structures.

Infectious bursal disease virus↗
PubMed1987

Serial sonograms to detect pancreatitis in children receiving L-asparaginase.

The clinical, laboratory, and ultrasonographic findings in children receiving L-asparaginase therapy were retrospectively reviewed and correlated to determine the diagnostic reliability and clinical usefulness of serial pancreatic sonograms in detecting L-asparaginase-induced pancreatitis. A total of 217 sonograms were obtained in 92 patients. Six of the 92 (6.5%) had L-asparaginase-induced pancreatitis. The diagnosis of pancreatitis was based solely on clinical symptoms in three patients, on clinical and laboratory findings in two, and on sonographic and laboratory findings in one. No confirmed cases of pancreatitis were detected solely by ultrasonography before clinical or laboratory evidence was obtained. Sonograms were useful only in confirming clinical and/or laboratory evidence of pancreatitis, but were of no value in making the early or preclinical diagnosis of drug-induced pancreatitis. We have discontinued the practice of obtaining routine serial pancreatic sonograms in children receiving L-asparaginase at our institution.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Progressive ascending paralysis following administration of intrathecal and intravenous cytosine arabinoside. A Pediatric Oncology Group study.

Two childhood acute myelogenous leukemia (AML) patients receiving intrathecal (IT) and intravenous (IV) cytosine arabinoside (Ara-C) developed progressive ascending paralysis, resulting in death in one patient. Necropsy findings on this patient included spinal cord demyelination characteristic of Ara-C neurotoxicity. An unusual aspect of these two cases was the delay between cessation of IT therapy and the onset of neurologic symptoms. These patients received relatively low total doses of IT Ara-C and standard doses of IV Ara-C. Previous studies have shown that Ara-C equilibrates readily between serum and cerebrospinal fluid; this implies that total IV and IT doses of Ara-C may be additive in relation to development of neurotoxicity. For these reasons, use of IV and IT Ara-C in childhood AML must be approached with greater caution, especially if neurologic abnormalities develop during or after therapy.

Acute Disease↗
PubMed1986

A polyoma-like virus associated with an acute disease of fledgling budgerigars (Melopsittacus undulatus).

A virus previously isolated from fledgling budgerigars (Melopsittacus undulatus) suffering from an acute disease, has been purified and the structural characteristics have been determined. The virions with a buoyant density of 1.34 g/ml are non-enveloped icosahedral particles with a diameter of about 46-48 nm. Their DNA genome has a molecular weight of about 3.3 X 10(6) d, and exists as supericoiled circular, relaxed circular, and linear molecules. There are eight structural proteins, the most abundant of which has a molecular weight of about 42,000 d. Empty capsid shells with buoyant densities of 1.31 g/ml are similar in size and shape, but lack DNA and histone-like polypeptides. Virus replication in chicken embryo cells results in cytopathic changes characterized by rounding and enlargement of the nucleus, and formation of intranuclear inclusion bodies. All these properties justify classification of the virus as polyoma-like.

Animals↗
PubMed1984

Cellular DNA content as a predictor of response to chemotherapy in infants with unresectable neuroblastoma.

We studied the relation between the DNA content of neuroblastoma cells and the response to therapy in 35 infants under one year of age with a diagnosis of neuroblastoma. Using flow cytometric techniques, we found that in 27 cases the primary malignant stem line consisted of neuroblasts with hyperdiploid DNA content, ranging from 1.07 to 2.42 times the finding in normal diploid cells. All remaining cases had diploid stem lines. Diploidy was more common in infants with clinical Stage D neuroblastoma (metastases beyond regional lymph nodes) than in those with other, less advanced stages: 6 of 10 as compared with 2 of 25 (P = 0.003). Of 17 evaluable patients with unresectable hyperdiploid tumors, 15 had complete responses and two had partial responses to cyclophosphamide and doxorubicin; six others with diploid tumors did not respond (P = 0.00001). We also found that each of the four infants with Evans' Stage IV-S neuroblastoma, an unusual form of disseminated neuroblastoma with a relatively good prognosis, had hyperdiploid tumor cells of clonal origin. We conclude that in neuroblastoma of infants, hyperdiploidy of tumor cells is associated with a better response to chemotherapy than is diploidy.

Cyclophosphamide↗
PubMed1983

Neuroblastoma: therapy for infants with good prognosis.

Therapy was designed to achieve a high cure rate and to prevent serious therapeutic side effects for 11 infants younger than one year old with neuroblastoma who had a favorable prognosis (Evans Stages I, II, III, and IV-S). It consisted of surgery alone if the tumor was totally removed (one infant) and of surgery and low doses of cytoxan and vincristine for a period of 1 year if the tumor was incompletely removed (seven infants). In addition, radiation therapy was applied to unresected dumbbell tumors (three infants). All infants are alive without evidence of disease with the exception of one who died in an accident. The follow-up time varies from 2-8 years. The drug combination prevented recurrences in two infants whose tumor was reduced by surgery to less than 10% of the original size. In five infants, chemotherapy reduced the size of large residual tumor masses. Two of these masses were subsequently removed. The tumors of the three other infants recurred while on chemotherapy and were successfully eradicated by surgery or radiation therapy. Two infants were not treated according to this therapeutic plan. Although they had small residual masses after surgery, no chemotherapy was given. They are alive without recurrence of the disease 2 years or more after diagnosis. In summary, cure was achieved in these infants without intensive chemotherapy.

Cyclophosphamide↗
PubMed1983

High-dose methotrexate as part of remission maintenance therapy for childhood acute lymphocytic leukemia: a Pediatric Oncology Group pilot study.

Seventeen children with acute lymphocytic leukemia (ALL) in remission were treated with parenteral high-dose methotrexate (HDM) pulses every eight weeks during standard 6-mercaptopurine and methotrexate (MTX) oral maintenance therapy. MTX (1,000 mg/m2) was infused over one hour followed by one hour of intravenous hydration for the purpose of achieving plasma and cerebrospinal fluid (CSF) levels greater than 10(-6) M for a period of 24 hours. Leucovorin (15 mg/m2) was administered orally six, 12, and 18 hours after completion of the HDM. Plasma and CSF concentrations of MTX were evaluated serially in the first 48 hours. During the first 24 hours, the plasma MTX level was maintained at greater than 10(-6) M. The patients receiving intrathecal MTX at a dose of 15 mg/m2 had an adequate, sustained MTX level in the CSF, but when no intrathecal MTX was administered, the CSF levels were less than 10(-6) M. For that reason, intrathecal MTX in a low dose (6 mg/m2) was injected intrathecally one hour after the HDM infusion, allowing the MTX level in CSF to approximate 10(-6) M over the 24 hours. The toxicity of this therapy was minimal. Due to the facts that the plasma and CSF MTX levels could be sustained above the desired concentrations and this regimen could be given in the outpatient clinic, this program has been incorporated into an ongoing study in an effort to prolong complete remissions.

Adolescent↗
PubMed1982

Therapeutic choices made by patients with end-stage cancer.

The Oklahoma Children's Memorial Hospital Oncology Service has developed a new approach for its patients with end-stage cancer. The emphasis is on the patients' acknowledgement of the progression of the disease and the imminence of death, and informed choice between the use of research drugs and no further chemotherapy. Forty-three patients between 6 and 20 years of age participated in a conference of this type. The results demonstrated that they understood that their health was declining. They decided about further therapy autonomously or together with their family. The majority of children who chose supportive care without chemotherapy and lived for a period of time, participated in activities at home as far as their state of health permitted. Severe depression and severe behavioral problems occurred rarely. There was evidence that this open approach enabled patients and family members to communicate openly with each other.

Adolescent↗