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Biomedical subjects

M Schiller

Publications and source records attributed to M Schiller.

At least 37 records · Page 2Linked to original sources
PubMed1999

Evaluation of anterior knee joint instability with the Rolimeter. A test in comparison with manual assessment and measuring with the KT-1000 arthrometer.

We report on a comparative measurement of anterior knee joint laxity on 30 healthy test subjects and 30 patients with anterior knee joint instability using a new knee testing device (Rolimeter) and the KT- 1000 arthrometer compared to manual assessment of the anterior tibial translation in 30 degrees flexion (Lachman's test). We wanted to establish the reliability of the Rolimeter device compared to manual assessment and to the KT- 1000 arthrometer. The statistical evaluation by means of an analysis of variance (ANOVA) at a significance level of 5% showed no significant difference in the exactitude of measurement between the Rolimeter and the KT-1000 arthrometer, but altogether a significant difference between both instrumental methods compared with manual assessment. Thus the Rolimeter provides an economic, exact and simply operating device for quantifying anterior knee joint instability.

Adolescent↗
PubMed1999

Molecular genetic alterations in radiation-induced astrocytomas.

Astrocytic tumors occasionally arise in the central nervous system following radiotherapy. It is not clear if these gliomas represent a unique molecular genetic subset. We identified nine cases in which an astrocytoma arose within ports of previous radiation therapy, with total doses ranging from 2400 to 5500 cGy. Irradiated primary lesions included craniopharyngioma, pituitary adenoma, Hodgkin's lymphoma, ependymoma, pineal neoplasm, rhabdomyosarcoma, and three cases of lymphoblastic malignancies. Patients ranged from 9 to 60 years of age and developed secondary tumors 5 to 23 years after radiotherapy. The 9 postradiation neoplasms presented as either anaplastic astrocytoma (3 cases) or glioblastoma multiforme (6 cases). Two of the latter contained malignant mesenchymal components. We performed DNA sequence analysis, differential polymerase chain reaction (PCR), and quantitative PCR on DNA from formalin-fixed, paraffin-embedded tumors to evaluate possible alterations of p53, PTEN, K-ras, EGFR, MTAP, and p16 (MTS1/CDKN2) genes. By quantitative PCR, we found EGFR gene amplification in 2 of 8 tumors. One of these demonstrated strong immunoreactivity for EGFR. Quantitative PCR showed chromosome 9p deletions including p16 tumor suppressor gene (2 of 7 tumors) and MTAP gene (3 of 7). Five of 9 tumors demonstrated diffuse nuclear immunoreactivity for p53 protein. Sequencing of the p53 gene in these 9 cases revealed a mutation in only one of these cases, a G-to-A substitution in codon 285 (exon 8). Somewhat unexpectedly, no mutations were identified in PTEN, a commonly altered tumor suppressor gene in de novo glioblastoma multiformes. Unlike some radiation-induced tumors, no activating point mutations of the K-ras proto-oncogene or base pair deletions of tumor suppressor genes were noted. These radiation-induced tumors are distinctive in their high histological grade at clinical presentation. The spectrum of molecular genetic alterations appears to be similar to that described in spontaneous high grade astrocytomas, especially those of the de novo type.

Adolescent↗
PubMed1998

Parathyroid adenoma after radiation in an 8-year-old boy.

We describe an 8-year-old boy who had asymptomatic hypercalcemia 4 years after radiotherapy involving the left orbit and lungs. A right parathyroid adenoma was diagnosed, and normocalcemia was achieved after its removal. Routine monitoring of serum calcium and phosphate levels is recommended for children after head and neck irradiation.

Adenoma↗
PubMed1998

Role of frontal cortex in social odor discrimination and scent-marking in female golden hamsters (Mesocricetus auratus).

Orbital/agranular insular (ORB/AI) cortex has been implicated in traditional olfactory learning tasks and social behavior but its precise role in discriminating-learning social odors is not known. Female golden hamsters received aspiration lesions of ORB/AI or dorsomedial (DM) frontal cortex and were tested for their ability to (a) discriminate between odors of individual males in a habituation-discrimination task, (b) show preferences for male over female odors, and (c) scent-mark in response to male odors. Lesioned females readily discriminated between scents of individual males. Neither lesion altered female preferences for male odors. Females with DM lesions showed increased levels of scent marking to male odors, but those with ORB/AI cortex lesions did not differ from controls. Thus, ORB/AI cortex does not appear to be critical for discrimination of odors of individuals or sex or for scent-marking responses based on these discriminations.

Animals↗
PubMed1998

[The semitendinosus tendon as replacement for the anterior cruciate ligament].

This article describes the history, advantages, biomechanical properties, operative technique, and results of replacement of the anterior cruciate ligament using the semitendinosus tendon. After arthroscopic ACL replacement using the doubled semitendinosus tendon in combination with an extraarticular lateral repair in 65 consecutive patients (20 acute, 45 chronic instabilities) we found after 2 years in 51 patients (78%) an excellent or good result with less than 3 mm difference in the Lachman test measured with the KT-1000 arthrometer (MMD). After 6 years 40 out of the 45 patients with chronic instabilities could be examined again. Only 28 patients (70%) showed a difference in anterior translation of less than 3 mm. A positive pivot shift sign could be seen in 11% of the patients after 2 years and in 20% after 6 years. The Tegner score increased from 6.0 after 2 years to 6.2 after 6 years, the Lysholm score decreased from 93 to 91 in the same interval. 89% of the patients had a free range of knee motion after 2 years and 92.5% after 6 years. There were 10% normal, 50% nearly normal, 25% abnormal, and 15% severely abnormal knees in the IKDC evaluation after 6 years. In the last 4 years we are using the quadrupled semitendinosus tendon in an arthroscopic single incision technique for ACL replacement with femoral Endobutton fixation, because the doubled semitendinosus tendon seems to elongate over time. After 23 months on average (12-36 months) the preoperative anterior translation of 7.5 mm could be decreased to 1.9 mm in 35 patients.

Anterior Cruciate Ligament↗
PubMed1997

Aortic stenosis in hypoplastic right heart syndrome, associated with interstitial deletion of chromosome 2.

This report describes a rare case of moderate to severe valvular aortic stenosis in the setting of severe tricuspid stenosis, pulmonary atresia with intact interventricular septum and right ventricular dependent coronary circulation. We discuss the clinical, hemodynamic, echocardiographic and angiocardiographic findings on this rare case and comment on accompanied malformations, with its possible association observed to the interstitial deletion of band q22 or q24 of the long arm of chromosome 2.

Abnormalities, Multiple↗
PubMed1997

Defects of insulin and IGF-1 action at receptor and postreceptor level in a patient with type A syndrome of insulin resistance.

The action of insulin and IGF-1 in comparison to non-diabetic controls was studied in cultured fibroblasts of a patient with an inherited syndrome of insulin resistance (Type A syndrome). Insulin binding was reduced due to decreased receptor affinity, but sequence analyses revealed no alterations of splicing or primary insulin receptor (IR) structure. Most likely due to the IR affinity defect analyses of signal transduction pathways showed an impairment of insulin action on glucose uptake, total RNA synthesis and phosphorylation as well as activity of MAP-kinase. In addition inducibility of c-fos mRNA level was strongly impaired by insulin and IGF-1, but comparable to controls by PDGF indicating a postreceptor defect. In conclusion, we provide evidence that genetic syndromes of insulin resistance can be associated with both, receptor and postreceptor defects.

Cells, Cultured↗
PubMed1997

High-level expression of the prohormones proenkephalin, pro-neuropeptide Y, proopiomelanocortin, and beta-protachykinin for in vitro prohormone processing.

Prohormone substrates are required for investigation of the proteolytic processing of prohormones and proproteins into active peptide hormones and neurotransmitters. However, the lack of prohormone proteins has been a limiting factor in elucidating proteolytic mechanisms for conversion of prohormones into active peptides. Therefore, in this study, cloned cDNAs encoding the prohormones proenkephalin (PE), pro-neuropeptide Y (pro-NPY), pro-opiomelanocortin (POMC), and beta-protachykinin (beta-PT) were utilized to express recombinant prohormones in Escherichia coli. High-level expression of milligrams of prohormones was achieved with the pET3c expression vector utilizing the T7 promoter for production of PE, pro-NPY, and POMC, as demonstrated by SDS-PAGE gel electrophoresis, Western blots, and 35S-methionine labeling. In addition, beta-PT was expressed at high levels as fusion proteins with the maltose-binding protein and glutathione S-transferase by the pMAL-c and pGEX-2T expression vectors, respectively. Relative rates of processing by the established processing proteases "prohormone thiol protease" (PTP), 70-kDa aspartyl protease, and PC1/ 3 and PC2 (PC, prohormone convertase) were examined with purified PE, pro-NPY, and POMC. Distinct preferences of processing enzymes for different prohormones was demonstrated. PTP preferred PE and pro-NPY substrates, whereas little processing of POMC was detected. In contrast, the 70-kDa aspartyl protease cleaved POMC more readily than pro-NPY or PE. However, PC1/3 and PC2 prefer POMC as substrate. Demonstration of selectivity of processing enzymes for prohormone substrates illustrates the importance of expressing recombinant prohormones for in vitro processing studies.

Animals↗
PubMed1997

[Hypomelanosis guttata idiopathica].

A 37-year-old white female with dark complexion presented with progressive hypopigmented macules on the face and upper trunk. She was in good health and her family history was unremarkable. Histologic examination of the hypopigmented patches revealed reduced melanin within the basal layers of the epidermis. Using immunohistochemical and ultrastructural studies, the number of melanocytes appeared normal but signs of degeneration were evident and dendrites were shortened. The diagnosis of idiopathic guttate hypomelanosis was established. The clinical picture, etiology and treatment of this relatively common but often unrecognized skin disease is discussed.

Adult↗
PubMed1996

Intracellular retention of cytosine arabinoside triphosphate in blast cells from children with acute myelogenous and lymphoblastic leukemia.

The importance of the cellular pharmacokinetics of cytarabine triphosphate (ara-CTP) with regard to therapeutic efficacy is well established. In vitro and in vivo monitoring of pharmacokinetic parameters of leukemic blast cells were initiated in order to contribute to the pharmacological basis of optimal ara-C treatment strategies. Peripheral or bone marrow blast cells from 66 leukemic patients [51 acute myelogenous leukemia (ALL), 15 acute lymphoblastic leukemia (AML) were separated and incubated with ara-C for 1 hour and in ara-C-free medium for another 3 hours, and the intracellular formation and retention of ara-CTP was measured. In eight children who received continuous ara-C infusion for induction treatment, the ara-CTP concentration in circulating blast cells was monitored in vivo. The in vitro values observed in this assay corresponded to the cellular levels monitored in vivo. The ara-CTP retention differed clearly among the individual groups, as classified by immunophenotype at the time of the initial diagnosis: non-T-ALL 67+/-25% (x+/-SD, n=33), T-ALL 37+/-15% (n=8), and AML 34+/-18% (n=14). The difference in ara-CTP retention between non-T-All and AML (P<0.05) as well as T-ALL (P<0.05) was significant. There was a tendency toward lower ara-CTP retention in relapsed as compared with newly diagnosed ALL, but the difference was not significant. The maximal accumulation of ara-CTP (after 1 hour incubation) was comparable in AML, T-ALL, non-T-ALL, and blast cells from children in relapse. The observed similarity of cellular accumulation in all groups and the significantly more rapid decrease in T-ALL and AML provide the pharmacokinetic rationale supporting the prolonged infusion duration for ara-C in these subgroups as an alternative to the intensification by high-dose ara-C schedules with short-term infusion.

Adolescent↗
PubMed1996

Familial combined duodenal and jejunal atresia.

Combined duodenal and jejunal atresia is extremely uncommon. The familial occurrence of congenital duodenal and small bowel atresia is even more unusual. To the authors' knowledge, this is the first report of two siblings with simultaneous duodenal and jejunal atresia who underwent successful surgical repair. The report may support the genetic origin of some forms of high intestinal atresia.

Abnormalities, Multiple↗
PubMed1995

[Hepatosplenic fungal abscesses in the immunocompromised].

A rare, newly recognized variant of systemic fungal infection is the occurrence of focal hepatosplenic microabscesses in the immunocompromised patient. A patient with persistent unexplained fever should have a CT or ultrasound scan of the abdomen. The presence of multiple splenic lesions strongly suggests fungal disease. If antifungal therapy does not result in complete resolution of fever and splenic lesions, splenectomy is recommended.

Abdomen↗
PubMed1995

Characteristics of the chromaffin granule aspartic proteinase involved in proenkephalin processing.

Proteolytic processing of neuropeptide precursors is required for production of active neurotransmitters and hormones. In this study, a chromaffin granule (CG) aspartic proteinase of 70 kDa was found to contribute to enkephalin precursor cleaving activity, as assayed with recombinant ([35S]Met) preproenkephalin. The 70-kDa CG aspartic proteinase was purified by concanavalin A-Sepharose, Sephacryl S-200, and pepstatin A agarose affinity chromatography. The proteinase showed optimal activity at pH 5.5. It was potently inhibited by pepstatin A, a selective aspartic proteinase inhibitor, but not by inhibitors of serine, cysteine, or metalloproteinases. Lack of inhibition by Val-D-Leu-Pro-Phe-Val-D-Leu--an inhibitor of pepsin, cathepsin D, and cathepsin E--distinguishes the CG aspartic proteinases from classical members of the aspartic proteinase family. The CG aspartic proteinase cleaved recombinant proenkephalin between the Lys172-Arg173 pair located at the COOH-terminus of (Met)enkephalin-Arg6-Gly7-Leu8, as assessed by peptide microsequencing. The importance of full-length prohormone as substrate was demonstrated by the enzyme's ability to hydrolyze 35S-labeled proenkephalin and proopiomelanocortin and its inability to cleave tri- and tetrapeptide substrates containing dibasic or monobasic cleavage sites. In this study, results provide evidence for the role of an aspartic proteinase in proenkephalin and prohormone processing.

Amino Acid Sequence↗
PubMed1995

Markers of coagulation activation for evaluation of the antithrombotic efficacy of heparin: a prospective study in acute deep venous thrombosis.

The potential value of measurements of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complexes (TAT) and D-dimer for the assessment of antithrombotic efficacy of heparin in acute deep venous thrombosis (DVT) was prospectively investigated. These variables were determined at presentation and subsequently once daily during a course of seven days heparin therapy. Heparin doses were adjusted according to the activated partial thromboplastin time (APTT). Compression ultrasonography was performed at presentation and on day 7 to determine the extent of thrombosis according to a predefined score. Out of a total of 50 patients accrued to the study 44 patients had reduced or unchanged extent of thrombosis, whereas in six patients an extension was documented. Although thrombin generation was significantly inhibited after initiation of heparin therapy as reflected by a decrease in F1 + 2 and TAT levels, these markers were not useful for the detection of patients with DVT extension. In contrast, anti-factor-Xa activities but not APTT measurements were significantly lower in the group of patients with propagation of DVT (median: 0.22 U/ml versus 0.38 U/ml, interquartile range: 0.1-0.33 U/ml versus 0.19-0.55 U/ml; P = 0.001). D-dimer decreased within the first days of heparin therapy but failed to indicate DVT progression. These data suggest that plasma anti-factor-Xa activity correlates better with the antithrombotic efficacy of heparin than APTT measurements and markers of coagulation or fibrinolysis activation.

Adult↗
PubMed1995

Cognitive sequelae of treatment in childhood acute lymphoblastic leukemia: cranial radiation requires an accomplice.

PURPOSE: We evaluated cognitive sequelae of treatment for childhood acute lymphoblastic leukemia (ALL). CNS therapy consisted of cranial irradiation (CRT) or no radiation. Children were also randomized to single intravenous high-dose methotrexate (HD-MTX) or conventional-dose methotrexate (CD-MTX) during induction, and all patients received intrathecal (IT) and systemic continuation chemotherapy. PATIENTS AND METHODS: Sixty-six patients treated for ALL on Dana-Farber Cancer Institute protocol 87-01 were evaluated by standardized cognitive and achievement tests. These children had been assigned at diagnosis to a standard-risk (SR) or high-risk (HR) group and received no CRT or 18 Gy CRT, respectively. All patients were randomized to receive MTX during remission induction, either as CD-MTX (40 mg/m2) or HD-MTX (4 g/m2) with leucovorin rescue. RESULTS: There was no difference in cognitive outcomes between radiated and unirradiated patients (P > .4). However, the HD-MTX/CRT combination was associated with decreased intelligence quotient (IQ estimate, 9.3 points) for girls only (P < .08). A specific deficit in verbal coding and memory was documented for all patients (P < .0001). CONCLUSION: We conclude the following: (1) 18 Gy CRT per se was not an independent toxic agent for cognitive outcome; (2) HD-MTX during induction was associated with IQ decline in girls, but only when it was followed by CRT; and (3) impairment of verbal memory and coding was a consistent finding that was independent of CRT, which implicates some component of chemotherapy, possibly prednisone, as a CNS toxin.

Analysis of Variance↗