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Biomedical subjects

M A Simon

Publications and source records attributed to M A Simon.

At least 127 records · Page 7Linked to original sources

Staging systems for musculoskeletal neoplasms.

In the treatment of musculoskeletal neoplasms, preservation of limb function and prolongation of survival have improved over the past decade. With the current emphasis on limb salvage procedures for local control of tumors, and with the addition of adjunctive therapy, the ability to classify and stage these unusual tumors is important in determining prognosis and treatment. In such classifications, a number of prognostic factors are identified and used to define stages. Three recognized staging systems exist for sarcomas of soft tissues and two for sarcomas of bone; there is one system for benign tumors of bone. The prognostic variables used in assigning stages are common to all of these systems, but the relative significance assigned to these variables differs. Documented improvement in survival and preservation of function suggests that current staging systems are significantly affecting outcome in the management of musculoskeletal tumors.

Bone Neoplasms↗

Studies of the retinoblastoma gene in human sarcomas.

The retinoblastoma susceptibility gene, (RB), is a tumor suppressor gene which, when deleted is associated with the development of retinoblastoma. The observation that children with heritable retinoblastoma frequently develop second malignancies, principally sarcomas, led to the detection of similar RB gene deletions in some osteosarcomas. We studied 44 unselected sarcomas from patients with no antecedent retinoblastoma to determine the prevalence and nature of RB gene alterations. DNA and RNA were extracted from fresh tumors and analysed by Southern and Northern blotting. Three of nine osteosarcomas and 4 of 29 soft-tissue sarcomas had deletions of the RB gene. Four of these were full-length, and three were partial deletions of the gene. RNA from 5 of the 7 deleted tumors was studied, and 4 cases completely lacked the RB transcript. Transcripts were found in 19 of 20 tumors with an apparently intact RB gene, and in all the normal tissues studied. An additional tumor lacked the RB transcript, but the gene appeared intact at the DNA level. In total, 8 of 38 sarcomas were found to have alterations of the RB gene. These data indicate that the RB gene is inactivated in a significant number of sarcomas unrelated to retinoblastoma, and that the potential role for the gene in the pathogenesis of human malignancy may not be limited to retinoblastoma.

Adolescent↗

In vitro radiobiological parameters of human sarcoma cell lines.

In vitro radiobiologic survival parameters have been determined for 7 human osteosarcoma, 5 human soft tissue and bone sarcomas, and 4 Ewing's sarcoma cell lines. The mean D0 values were 99.5 +/- 11.6 cGy, 90.5 +/- 7.7 cGy and 95.8 +/- 7.9 cGy for osteosarcomas, soft tissue and bone sarcomas and Ewing's sarcomas, respectively. These in vitro survival data do not predict the clinical radiation resistance generally attributed to osteosarcomas and soft tissue and bone sarcomas, and do not differ substantially from the results obtained with the clinically radioresponsive Ewing's sarcomas.

Bone Neoplasms↗

Chondroblastoma: an immunohistochemical study.

Five chondroblastomas were examined for the presence of monocyte/macrophage-associated antigens by an alkaline phosphatase-anti-alkaline phosphatase immunohistochemical method. The tumor cell populations were analyzed with eight antibodies reacting with separate antigens on cells of monocyte/macrophage lineage and with antibodies directed against glycoprotein IIIa and factor VIII. The "chondroblastic" tumor cells did not stain with any of the macrophage-associated antibodies. Osteoclast-like giant cells stained with the macrophage-associated antigens EBM11, KB90, leukocyte common antigen, and with the megakaryocyte/platelet-associated antigen C17. Only endothelial cells were reactive with antibody to factor VIII. Our data do not support the postulated histiocytic origin of the neoplastic cells within chondroblastomas; the osteoclast-like giant cells present within these tumors are felt to be both reactive and of monocyte/macrophage lineage.

Adolescent↗

Nucleotide sequence and structure of the sevenless gene of Drosophila melanogaster.

In the Drosophila melanogaster mutant sevenless, the R7 photoreceptor in each of the repeating units, or ommatidia, of the compound eye fails to form. We have determined the nucleotide sequence and structure of the sevenless transcription unit. Overlapping cDNA clones from an eye imaginal disc library were isolated, and these together with corresponding genomic regions were sequenced. The positions of the major and two minor transcription start sites were mapped. The gene encodes a putative cell-surface receptor, the unmodified form of which is predicted as 288 kD, bearing a cytoplasmic tyrosine kinase domain. Several structural features distinguish sevenless from other tyrosine kinase receptors, most notably the large size of its extracellular domain. Moreover, unlike the insulin or epidermal growth factor (EGF) receptors, a putative amino-terminal signal sequence does not immediately follow the initiating methionine codon. Rather, a 21-amino-acid hydrophobic sequence is found 56 amino acids after the likely initiating methionine codon, suggesting that this sequence may function as an amino-terminal anchor. If so, the sevenless protein would be expected to have its 2001-amino-acid extracellular domain anchored as a loop at either end in the membrane. Finally, we have generated a number of transformant lines that carry either a 16.3-kb genomic fragment that extends approximately 950 bp upstream of the transcription start sites or constructs in which a subset of the introns present in the genomic sevenless DNA have been removed. The degree of rescue of the sevenless mutant phenotype has been assayed in these lines using morphological and behavioral assays.

Amino Acid Sequence↗

Binding and antilipolytic action of insulin in isolated adipocytes from cortisol-treated rats.

The effects of an in vivo cortisol-treatment to rats (2 X 2 mg/rat/day, for one week) on insulin plasma levels, insulin binding and antilipolytic activity in rat adipose tissue were investigated. Hyperinsulinemia together with an increase in insulin degradation in the serum of cortisol-treated rats were observed. The adipocytes from cortisol-treated animals showed a statistically significant decrease in insulin binding but no change in receptor numbers [cortisol-treated 103,000 +/- 8,000 (n = 8) receptors/cell and controls 138,000 +/- 15,000 (n = 16) receptors/cell], together with unchanged receptor affinity [ED50: cortisol-treated 3 X 10(-9) M and controls 3.2 X 10(-9) M], and a decreased sensitivity to the antilipolytic effect of insulin. The evidence presented for pre-receptor, receptor and post-receptor insulin defects on the action of cortisol in isolated rat adipocytes could represent a coordinated mechanism by which cortisol exerts "insulin resistance" in this tissue.

Adipose Tissue↗

Musculoskeletal tumors: improved depiction with linear combinations of MR images.

With postprocessing, the authors produced a single hybrid image that combines the complementary information in conventional T1- and T2-weighted magnetic resonance (MR) images. A 1-T MR imager was used to produce T1- and T2-weighted images (repetition time, msec/echo time, msec: 500/30, 1,500/120) of patients with various primary bone tumors. Various weighted sums and differences of these images were then formed. Weighted subtraction allowed formation of hybrid images with high contrast between tumor and all adjacent normal tissues (muscle, fat, bone marrow), unlike the original T1- and T2-weighted images. Certain weighted sums of the acquired images simultaneously display the high signal-to-noise and clear anatomic detail of the T1-weighted technique along with the high contrast between extraosseous tumor and muscle of the T2-weighted image. A single hybrid MR image can contain useful characteristics both of T1- and T2-weighted images, making it easier for one to detect the extent of an abnormality.

Bone Neoplasms↗

Disparate histologic responses in simultaneously resected primary and metastatic osteosarcoma following intravenous neoadjuvant chemotherapy.

Seven patients with newly diagnosed metastatic osteosarcoma underwent simultaneous resection of the primary tumor and metastases following intravenous (IV) neoadjuvant chemotherapy. Histologic response was assessed in all tumor specimens. Disparate responses were noted between primary tumor and metastases and, in some cases, between two or more metastatic tumor deposits. The diverse histologic response to neoadjuvant chemotherapy suggests tumor cell heterogeneity. Changing postoperative therapy on the basis of the histologic response induced in the primary tumor may not be appropriate.

Adolescent↗

Primary bone tumors in children.

The combination of clinical information and the findings on conventional radiographs should lead the physician to a narrow differential diagnosis. Before biopsy, appropriate diagnostic and staging studies should be carried out. The biopsy reveals the pathologic diagnosis and a definitive treatment plan then can be instituted. An algorithm is provided for the evaluation and treatment of a child with a suspected bone tumor (Fig. 14).

Adolescent↗

Scintigraphy with gallium-67 citrate in staging of soft-tissue sarcomas of the extremity.

We performed a retrospective study of sixty patients who had a soft-tissue sarcoma of the extremity to determine the usefulness of scintigraphy with gallium-67 citrate as a staging modality. Abnormal activity of the gallium was present in forty-one of forty-eight sites in which there was macroscopic primary tumor. In six of the forty-eight patients, the imaging demonstrated non-pulmonary metastases that had not been detected by any other staging studies. Scintigraphy with gallium-67 citrate should be employed routinely for staging of soft-tissue sarcomas because of its utility in detecting non-pulmonary metastases that are not otherwise detected on routine staging studies.

Adolescent↗

Continuous venous infusion of doxorubicin in advanced sarcomas.

Seventeen patients with advanced sarcoma were treated with continuous venous infusion of doxorubicin for a mean of 118 days, achieving total doses up to 1097 mg/m2. Three partial responses and one minor response were obtained. Major toxic effects were stomatitis and hand-foot syndrome. There was a low incidence of leukopenia (18%) and clinical cardiotoxicity (11%). Continuous venous infusion is a safe means of administering doxorubicin, with a response rate similar to that observed with bolus doxorubicin in metastatic sarcoma.

Adult↗

The malignant potential of enchondromatosis.

In a tri-institutional, retrospective study with long-term follow-up, forty-four patients who had multiple enchondromas were identified. Thirty-seven patients did not have hemangiomas (Ollier disease) and seven did (Maffucci syndrome). Of the thirty-seven patients who had Ollier disease, a low-grade chondrosarcoma developed in four; an astrocytoma, in one; and a granulosa-cell ovarian tumor, in one. In four of the seven patients who had Maffucci syndrome, there were six low-grade chondrosarcomas, one high-grade osteosarcoma, one pancreatic adenocarcinoma, one biliary adenocarcinoma, and one astrocytoma. None of the patients in either group died of the skeletal sarcoma, but four of five patients who had a non-skeletal malignant lesion died. From life-table analyses of these patients, we estimated that the incidence of secondary chondrosarcoma in patients who have Ollier disease is about 25 per cent at the age of forty years, and that malignant degeneration is almost a certainty in patients who have Maffucci syndrome. We concluded that periodic surveillance of the brain and abdomen for occult malignant lesions is indicated in patients who have enchondromatosis.

Adolescent↗

The search for the primary tumor in patients with skeletal metastases of unknown origin.

Forty-six patients who had been evaluated because of skeletal metastases of unknown origin, were reviewed. Twenty-six of the patients were referred to an orthopedic surgeon before confirmation of the metastases by biopsy; 20 others were referred to an oncology clinic after a diagnosis of bone metastases had been established. A simple diagnostic sequence consisting of a medical history, physical examination, routine laboratory studies, chest roentgenogram, technetium 99m phosphonate bone scintigram, and intravenous pyelogram identified the site of the primary tumor in 14 patients; 7 of the primaries were lung carcinomas, 4 were hypernephromas, 2 were breast carcinomas, and 1 was a prostate carcinoma. In two other patients, the histologic findings from the biopsy study were diagnostic; one had a thyroid carcinoma and one, a prostate carcinoma. Further extensive diagnostic workups revealed the site of origin in only four additional patients; two had hypernephromas which were discovered by computed axial tomography of the abdomen; one had an ovarian carcinoma and one had a hepatoma, both of which were found at laparotomy. On the basis of this study, a simple diagnostic strategy is recommended for patients with histopathologically confirmed skeletal metastases of unknown origin: medical history, physical examination, routine laboratory studies, chest radiograph, and technetium 99m phosphonate bone scintigram, followed by computed axial tomographic examination of the abdomen and pelvis. In female patients, it may be judicious to use mammography. If this regimen fails to reveal the primary site, it is unlikely that it will be identified with further extensive diagnostic procedures.

Adult↗

Current and lifetime incidence of psychiatric disorders among a group of extremity sarcoma survivors.

Thirty-five survivors of extremity sarcomas being followed in a University-Hospital orthopedic clinic were evaluated for current and lifetime presence of psychiatric disorders. Patients were assessed for cognitive abilities using the Cognitive Capacity Screening Examination and for psychiatric disorders using a structured interview format, the Schedule for Affective Disorders and Schizophrenia-Lifetime version. The criteria for psychiatric disorders were the Research Diagnostic Criteria. Two patients were excluded because of cognitive deficiencies; thirty-three patients (mean age = 37.7 yr) were formally evaluated at a mean time of 2.6 yr following cancer diagnosis and surgery. Forty-five per cent of patients were given the diagnosis of at least one lifetime psychiatric disorder. Fifteen per cent of patients reported a current episode. Affective disorders and alcoholism were the most frequently reported disorders.

Adaptation, Psychological↗