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Biomedical subjects

M A Simon

Publications and source records attributed to M A Simon.

At least 91 records · Page 5Linked to original sources
PubMed1994

Oncologic outcomes of primary bone sarcomas of the pelvis.

Although many studies have been performed for evaluation of surgical techniques and surgical morbidity in cases of primary pelvic sarcoma, few have addressed the long term oncologic outcomes for these patients. Therefore, the outcome of 41 patients with primary pelvic bone sarcomas were followed for 2-13 years (average, 6 years; median, 5 years). There were 18 chondrosarcomas (15 low grade and 3 high grade tumors), 11 osteosarcomas (1 low grade and 10 high grade tumors), 5 high grade malignant fibrous histiocytomas of bone, 5 Ewing's sarcomas, 1 undifferentiated sarcoma, and 1 low grade angiosarcoma of bone. Fifteen of the 17 patients with low grade tumors survived (88%), whereas only 6 of the 24 patients with high grade tumors survived (25%). Local disease recurred in 1 of the 24 (4%) patients with high grade tumors and in none of the patients with low grade tumors. Reoperations for complications were required in 33% of the patients. A difference could not be demonstrated in the quality of surgical margins or in the surgical morbidity, patient survival, and rate of local recurrence between patients treated with hemipelvectomy (8) and those treated with pelvic resection (32). Patients with low grade pelvic sarcomas have a good prognosis after pelvic resection, but those with high grade sarcomas continue to have a poor prognosis.

Adolescent↗
PubMed1994

Diagnostic strategy for bone and soft-tissue tumors.

The diagnostic strategy to be used for a bone tumor depends on the ability of the clinician to make an accurate differential diagnosis on the basis of clinical information and plain radiographs. The clinician must be able to classify the patient as having a non-progressive or a progressive primary benign bone tumor, a primary malignant bone tumor, or a metastatic bone tumor. Only after assignment to one of these four categories can an effective diagnostic strategy ensue. If the clinical and radiographic information favors a diagnosis of malignant or aggressive benign bone tumor, the clinician should refer the patient to an experienced orthopaedic oncologist without performing additional diagnostic tests or a biopsy. If a soft-tissue mass is 5 cm in diameter or larger on physical examination, and especially if it is deep to the fascia, the patient should also be referred to an orthopaedic oncologist, without additional evaluation or biopsy, because of the relatively high probability that the mass is malignant.

Bone Neoplasms↗
PubMed1993

Dedifferentiated chordoma. Response to aggressive chemotherapy in two cases.

BACKGROUND: Dedifferentiated chordoma is an unusual and aggressive variant of chordoma which is likely to metastasize. Few reports exist of treatment of these tumors with chemotherapy. METHODS: In 1988, two patients with dedifferentiated sacral chordomas were seen at the University of Chicago Hospitals. Both developed metastatic disease less than a year after sacral resection and radiation therapy. These patients' diagnoses, courses, and treatments were reviewed along with the literature on chemotherapy in both conventional and dedifferentiated chordomas. RESULTS: Both patients obtained complete remissions, one to a six-drug regimen and the other to ifosfamide. CONCLUSIONS: A trial of reasonably aggressive chemotherapy is warranted in patients with metastatic dedifferentiated chordoma. The optimum regimen is unclear, but agents active in high-grade sarcomas are logical choices.

Adult↗
PubMed1993

An SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro.

Activation of the sevenless protein-tyrosine kinase is required for the proper specification of R7 photoreceptors in the Drosophila eye. The activation of a Ras protein, p21Ras1, is a crucial early event in the signaling pathway, and constitutive activation of p21Ras1 is sufficient to induce all of the effects of sevenless action. Here we report that another gene, E(sev)2B, required for proper signaling by sevenless encodes a protein of the structure SH3-SH2-SH3. We further provide evidence that the E(sev)2B protein is required for activation of p21Ras1 but not for any subsequent events, and that this protein can bind in vitro to sevenless and to Son of sevenless (Sos), a putative guanine nucleotide exchange factor for p21Ras1. These results suggest that the E(sev)2B protein may act to stimulate the ability of Sos to catalyze p21Ras1 activation by linking sevenless and Sos in a signaling complex. We have renamed the E(sev)2B locus downstream of receptor kinases (drk).

Alleles↗
PubMed1993

An immunohistologic study of granulomatous inflammation in SIV-infected rhesus monkeys.

We studied granulomatous inflammation in simian AIDS using histologic, immunohistologic, and in situ hybridization techniques. Complete Freund's adjuvant was used to induce granulomas in two control animals and two macaques infected with simian immunodeficiency virus (SIV) and having low peripheral CD4+ T cell counts. Control animals developed large (> 2 cm diameter) epithelioid granulomas containing CD68+ macrophages (m phi s), epithelioid m phi s and multinucleated giant cells (MNGCs), CD4+ and CD8+ T cells, and small perivascular collections of CD20+ B cells. Lymphocytes rarely expressed proliferating cell nuclear antigen (Ki-67), and only rare endothelial cells expressed vascular cell adhesion molecule 1 (VCAM-1). In contrast, SIV+ animals had smaller (< 0.5 cm diameter) epithelioid granulomas characterized by numerous large, dense CD8+, CD20+ lymphocyte aggregates with prominent local division (Ki-67+). Despite low blood CD4+ T cell numbers, there was a substantial CD4+ T cell infiltrate, accompanied by enhanced endothelial VCAM-1 expression. These granulomas contained no detectable SIV antigen or RNA. Thus, in simian AIDS, experimentally induced granulomatous responses are grossly attenuated, yet associated with increased local endothelial-leukocyte signaling and lymphocyte division.

Animals↗
PubMed1993

Diagnostic strategy for bone and soft-tissue tumors.

The diagnostic strategy to be used for a bone tumor depends on the ability of the clinician to make an accurate differential diagnosis on the basis of clinical information and plain radiographs. The clinician must be able to classify the patient as having a non-progressive or a progressive primary benign bone tumor, a primary malignant bone tumor, or a metastatic bone tumor. Only after assignment to one of these four categories can an effective diagnostic strategy ensue. If the clinical and radiographic information favors a diagnosis of malignant or aggressive benign bone tumor, the clinician should refer the patient to an experienced orthopaedic oncologist without performing additional diagnostic tests or a biopsy. If a soft-tissue mass is five centimeters in diameter or larger on physical examination, and especially if it is deep to the fascia, the patient should also be referred to an orthopaedic oncologist, without additional evaluation or biopsy, because of the relatively high probability that the mass is malignant.

Bone Neoplasms↗
PubMed1993

Skeletal metastases of unknown origin. A prospective study of a diagnostic strategy.

We carried out a prospective study of the effectiveness of a diagnostic strategy in forty consecutively seen patients who had skeletal metastases of unknown origin. The diagnostic strategy consisted of the recording of a medical history; physical examination; routine laboratory analysis; plain radiography of the involved bone and the chest; whole-body technetium-99m-phosphonate bone scintigraphy; and computed tomography of the chest, abdomen, and pelvis. After this evaluation, a biopsy of the most accessible osseous lesion was done. The laboratory values were non-specific in all patients. The history and physical examination revealed the occult primary site of the malignant tumor in three patients (8 per cent): one patient who had carcinoma of the breast; one, of the kidney; and one, of the bladder. Plain radiographs of the chest established the diagnosis of carcinoma of the lung in seventeen patients (43 per cent). Computed tomography of the chest identified an additional six primary carcinomas of the lung (15 per cent). Computed tomography of the abdomen and pelvis established the diagnosis in five patients (13 per cent): three patients who had carcinoma of the kidney; one, carcinoma of the liver; and one, carcinoma of the colon. Examination of the biopsy tissue established the diagnosis in only three additional patients (8 per cent) and confirmed it in eleven others. On the basis of the biopsy alone, we were unable to identify the primary site of the malignant tumor in twenty-six (65 per cent) of the patients. In thirty-four (85 per cent) of the forty patients, the primary site was identified with the use of the diagnostic strategy described here, and only two additional occult malignant tumors were found on follow-up studies. Our diagnostic strategy was simple and highly successful for the identification of the site of an occult malignant tumor before biopsy in patients who had skeletal metastases of unknown origin.

Adult↗
PubMed1993

New 2-aryl-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-4-one derivatives as diuretics.

2-Aryl-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-4-one derivatives having various substituents at the 4'-position, H or methyl at 1,3-positions and nitro or amino at 6-position were prepared and tested for their diuretic, natriuretic and kaliuretic activities on male Wistar rats at a dosage of 25 mg/kg or less. 2-(3-Pyridyl) derivatives were inactive. 1,3-Dimethyl-6-nitro-2-phenyl derivatives (1) were active depending on the electronic character of the 4'-substituent but at the same time were sodium-sparing. However, 1(H),3(H)-6-nitro-2-phenyl derivatives (2) were generally inactive as diuretics but active as potassium-sparing drugs. 6-Amino-1(H),3(H)-2-phenyl derivatives (4) were active as diuretics depending on dipolar moment of the substituent at the 4'-position, and induced moderate potassium release. The 6-amino-2-(4-trifluoromethylphenyl)-1, 2,3,4-tetrahydropyrido [2,3-d]pyrimidin-4-one (4f) remained active up to a dosage of 3 mg/kg. The structure-activity relationships were carried out in light of the adaptative least squares (ALS) method and discriminant functions for diuretic compounds were established.

Animals↗
PubMed1993

Disseminated B virus infection in a cynomolgus monkey.

A cynomolgus monkey (Macaca fascicularis) was euthanatized 1 week following dystocia because of severe peritonitis. Histologic examination revealed lesions characteristic of herpesvirus infection in lungs, liver, spleen, bone marrow, uterus, and adrenal gland, and on the serosal surface of intestines, pancreas, and reproductive tract. Immunohistochemical studies on liver and lungs revealed Herpes B-like antigens in the lesions. B virus was isolated from serum. As systemic B-virus infection was not diagnosed before death of the monkey, these findings underscore the need for universal precautions when handling blood, fluids, or tissues from macaques.

Animals↗
PubMed1993

Principles of staging of soft-tissue sarcomas.

The TNM staging system is a modus for diagnosis and treatment in which T is the extent of the tumor involvement, N is lymph node involvement, and M is the metastases; this system is supplemented with a histologic malignancy grade. Staging systems identify specific prognostic factors with which to predict clinical outcome. Staging systems are useful for assigning treatment priorities, determining the role of adjuvant therapies, and evaluating clinical investigations. Unfortunately, no universally accepted staging system for soft-tissue sarcomas exists. This is related to the relatively low incidence of sarcomas, the unique and unpredictable behavior of sarcomas, significant disagreement regarding histogenesis and grading, and lack of consensus regarding the value of various prognostic factors. In adults, the two most commonly used staging systems are those developed by the American Joint Committee on Cancer and by Enneking. In children, the Intergroup Rhabdomyosarcoma Study and the International Union Against Cancer have described the systems most commonly used. These systems for soft-tissue sarcomas rely on an ability to accurately determine both the local and distant extent of disease. Advances in the field of computed tomography and magnetic resonance imaging have made this possible. It is likely that a staging system based upon a more sophisticated understanding of the basic biology of sarcomas will become available.

Adult↗
PubMed1992

The growth inhibitory action of melatonin on human breast cancer cells is linked to the estrogen response system.

The pineal hormone, melatonin, was examined for its capacity to modulate the proliferation of a panel of human breast cancer cell lines. Melatonin inhibited, to a varying extent, the proliferation of all three estrogen-responsive cell lines, but had no effect on estrogen-insensitive breast tumor cell lines. Melatonin was also able to specifically block estrogen-induced proliferation in MCF-7 breast cancer cells. However, this action was abolished in the presence of tamoxifen. Therefore, it appears that the antiproliferative effects of melatonin are mediated through the estrogen-response pathway.

Antineoplastic Agents↗
PubMed1992

Signalling by the sevenless protein tyrosine kinase is mimicked by Ras1 activation.

Cell-fate specification of R7 photoreceptors in the developing Drosophila eye depends on an inductive signal from neighbouring R8 cells. Mutations in three genes, sevenless (sev), bride-of-sevenless (boss) and seven-in-absentia (sina) cause the R7 precursor to become a non-neural cone cell. The sev gene encodes a receptor protein tyrosine kinase (Sev) localized on the R7 surface, activated by a boss-encoded ligand presented by R8. The sina gene encodes a nuclear factor required in R7. Reduction in the dosage of the Ras1 gene impairs Sev-mediated signalling, suggesting that activation of Ras1 may be an important consequence of Sev activation. We report here that Ras1 activation may account for all of the signalling action of Sev; an activated Ras1Va112 protein rescues the normal R7 precursor from transformation into a cone cell in sev and boss null mutants and induces the formation of supernumerary R7 cells. Similar activation of the Drosophila Ras2 protein does not produce these effects, demonstrating Ras protein specificity.

Animals↗
PubMed1992

Pathologic features of SIV-induced disease and the association of macrophage infection with disease evolution.

Since the original isolation of simian immunodeficiency virus (SIV) from a macaque with an AIDS-like disease, numerous studies have demonstrated the close biologic and genetic relationship of the SIVs to the HIVs. Probably most important, the clinical spectrum of disease associated with SIVmac/SIVsmm infection in rhesus monkeys is strikingly similar to AIDS in HIV-1-infected human beings. Herein are summarized the pathologic features of SIVmac-induced disease in a cohort of rhesus monkeys, with special reference to the role of infected macrophages in the development of AIDS-related manifestations.

Animals↗
PubMed1992

Clinical pharmacokinetics of R(+)- and S(-)-mepivacaine after high doses of racemic mepivacaine with epinephrine in the combined psoas compartment/sciatic nerve block.

The purpose of this study was to investigate the pharmacokinetics of R(+)- and S(-)-mepivacaine in 10 male patients after injection of a high dose (731 mg) of racemic R,S-mepivacaine for a combined psoas compartment/sciatic nerve block. Arterial blood samples were taken, and the plasma concentrations of the stereoisomers R(+)- and S(-)-mepivacaine were measured by means of high-performance liquid chromatography (HPLC) with a Chiral AGP column. The S(-) isomer reached higher plasma concentrations than the R(+) isomer. The maximal plasma concentration (Cmax) of R(+) was 1.54 +/- 0.34 micrograms/mL, whereas that of the S(-) isomer was 2.34 +/- 0.51 micrograms/mL (P = 0.00050). The time at which Cmax was reached (Tmax) was identical for both isomers. The area under the plasma concentration-time curve from t = 0 to infinity (AUC infinity) of S(-)-mepivacaine was almost double that of R(+)-mepivacaine. The elimination half-life (T1/2) was identical for both isomers (3 h), which means that the calculated total body clearance and the calculated steady-state volume of the distribution of R(+) are, respectively, 1.7 and 1.5 times larger than that of the S(-) isomer. We conclude that the plasma concentrations of the S(-)-mepivacaine isomer were higher than those of the R(+) isomer because of a smaller volume of distribution and a slower total body clearance.

Adult↗