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R Kandel

Publications and source records attributed to R Kandel.

At least 37 records · Page 2Linked to original sources

Aneurysmal cyst of soft tissue: report of a case with serial magnetic resonance imaging and biopsy.

We report a case of an extraosseous aneurysmal cyst arising in the left retroclavicular soft tissue of a 29-year-old woman. A magnetic resonance imaging (MRI) scan showed a solid lesion within soft tissue, abutting the clavicle without bone involvement. An incisional biopsy was interpreted as showing osteoclast rich nodular fasciitis with prominent vascularity. A second MRI 5 months later showed intralesional cystic change with areas of increased signal on T2-weighted images, still without any bony defect. The lesion was excised. Histological examination revealed large vascular spaces lined focally by giant cells. The remainder of the lesion was composed of an admixture of spindle cells and osteoclast-like giant cells. The histological and ultrastructural appearance was that of an aneurysmal bone cyst; however, in view of the lack of any bony involvement, a diagnosis of aneurysmal cyst of soft tissue was made. Primary aneurysmal cysts of soft tissue are rare; this is the third well-documented case in the literature, and the first to describe both the MRI appearance and the histological evolution from a solid to multiloculated lesion.

Adult↗

APOE4 genotyping.

Explore the source record for details and available documents.

Alzheimer Disease↗

Sarcoma of bone-cement membrane: a case report and review of the literature.

The development of a cancerous tumour at the site of total joint replacement is a rare but virtually always fatal event. The previously unreported scenario of a patient who was found to have a malignant fibrous histocytoma at the bone-cement membrane after revision for a loose total hip prosthesis is reported. Recent biologic information evaluating the response of mesenchymal cells to metallic debris suggests that the environment surrounding a loosened prosthesis may provide conditions appropriate for the development of a sarcoma.

Biopsy, Needle↗

Residual disease following unplanned excision of soft-tissue sarcoma of an extremity.

Sixty-five patients who had been referred to our unit for additional management after an unplanned excision of a soft-tissue sarcoma of an extremity at another institution were studied retrospectively to determine the prevalence of residual tumor and to identify factors that predict which patients will have a tumor following such an excision. Unplanned excision was defined as excisional biopsy or unplanned resection of the lesion without benefit of preoperative imaging and without regard for the necessity to resect the lesion with a margin of normal tissue. In each patient, histological evaluation of the specimen removed at the unplanned excision had demonstrated positive resection margins, but postoperative physical examination on our unit revealed no gross evidence of residual tumor and no tumor was identified on cross-sectional imaging of the local site. Patients who had evidence of residual disease on physical examination or on imaging were thought to have definite evidence of sarcoma at the site of the operative wound and were therefore excluded from the study. After multidisciplinary consultation, all patients had a repeat resection at our cancer center. Extensive pathological sampling of the specimen from this second procedure was carried out, with sections obtained at mean intervals of 1.2 +/- 0.7 centimeters. Nodules initially thought to indicate disease were identified grossly in twenty-seven (42 percent) of the sixty-five patients, but histological evaluation confirmed the presence of tumor in only sixteen (59 percent). Histological evidence of sarcoma was identified in seven additional patients in whom gross nodules were not apparent in the specimen. Thus, sarcoma was identified in a total of twenty-three (35 percent) of the sixty-five patients. The mean duration of follow-up was forty-six months (range, twenty-four to eighty months; median, thirty-nine months). The margins of the second resection were positive in nine (39 percent) of the twenty-three patients who had residual sarcoma. Five (22 percent) of the twenty-three had a local recurrence. Four of the five patients who had a local recurrence had positive margins on repeat resection. This rate of local recurrence (five of twenty-three patients) was significantly higher than that in the remainder of our patients who had a soft-tissue sarcoma of an extremity (sixteen [7 percent] of 227) (p = 0.03). There was no association between the detection of sarcoma at the second procedure and the initial size or grade of the tumor, the use of irradiation preoperatively, or the interval between the initial, unplanned excision and referral to our cancer center. These data indicate that it is not possible to predict which patients will have residual tumor at the site of the operative wound. Therefore, it is prudent to advise repeat excision for all patients who have had an unplanned excision of a soft-tissue sarcoma of an extremity. Unplanned excision complicates decision-making in the treatment of this disease and should be avoided.

Biopsy↗

Amyloid enhancing factor is produced by rats and amyloid-resistant CE/J mice.

Amyloid enhancing factor (AEF) is an operational term applied to poorly defined extracts of amyloidotic or preamyloidotic tissues capable of shortening the induction time of amyloid deposition in recipient mice from 1 to 2 weeks to 48 to 72 hours. Its derivation has always left open the question of whether activity was dependent on the presence of amyloid fibrils or preamyloid fibril fragments. In these studies, we have assayed AEF activity in extracts of spleen and liver from azocasein-injected rats and CE/J mice that do not develop amyloidosis and, hence, cannot have amyloid A (AA) fibrils or fibril fragments in their tissues. Susceptibility to amyloid induction was compared in three strains of mice and three strains of rats by subjecting each group of experimental animals to multiple injections of azocasein. Spleens and livers were removed 24 hours after the last injection, and samples of all tissues were examined for amyloid deposits. AEF was extracted from the remainder of the tissues taken from amyloid resistant CE/J mice and Sprague-Dawley rats. Graded doses of the resulting tissue extract were given to naive Swiss-Webster (SW) recipient mice by i.p. injection concomitantly with subcutaneous injection of 0.5 ml 2% AgNO3. All tissues from both CE/J mice and rat donor animals were negative for amyloid by histologic examination of Congo Red stained samples, as were the AEF extracts. All recipient mice (six of six) given 600 micrograms of the CE/J-derived AEF developed large amyloid deposits in their spleens (mean severity 3.7 -/+ 0.3 SEM). Lower doses (200 micrograms protein) resulted in similar incidence of amyloid accumulation (in four of five), but quantitatively smaller amounts of amyloid protein were present. Doses of 100 micrograms decreased incidence (in one of five), whereas animals receiving 50 micrograms were all negative. AEF derived from rat tissues also induced high incidence of amyloid (in four of five) at high doses, although the amount of AA protein was less than in mice given equivalent amounts of CE/J mouse-derived AEF. Although 200 micrograms and 100 micrograms of rat AEF was effective (in two of five and one of five, respectively), 50 micrograms did not result in demonstrable amyloid deposition. The presence of AEF in tissues from azocasein-treated amyloid-resistant rats and CE/J mice excludes the possibility that AEF activity may be due to the presence of amyloid fibrils or fibril fragments in the donor tissue.

Amyloid↗

Molecular and immunohistochemical identification of p53 alterations in bone and soft tissue sarcomas.

p53 has been shown to suppress tumor growth by regulating the cell cycle and by triggering apoptosis. Acquired somatic mutations of the p53 gene have been observed in a variety of human malignancies, and these result in a loss of its tumor suppressor function. To examine the occurrence of p53 abnormalities in bone and soft tissue sarcomas, 113 tumors were subjected to molecular analysis and mutations were confirmed in 16 tumors. The frequency of p53 alterations varied among the different subtypes of bone and soft tissue sarcomas, being observed predominantly in osteosarcomas (8/34 cases), rhabdomyosarcomas (2/3 cases), Ewing's sarcomas (1/5 cases), and liposarcomas (3/21 cases). In contrast, p53 gene mutations were detected at a lower frequency in malignant fibrous histiocytomas (2/34 cases) and not at all in nine chondrosarcomas and five leiomyosarcomas. Immunohistochemical staining of p53 protein was performed on 69 cases and compared to the DNA results. For 64 cases the results were concordant: 56 sarcomas were considered to have wild-type p53 by both techniques. As well, increased p53 protein expression was observed in eight of the nine tumors with p53 gene mutations. However, positive p53 staining was also seen in four sarcomas which had no detectable p53 mutations in exons 5 through 9. Because some sarcomas exhibit amplification and overexpression of MDM-2, which may interact with p53 and cause stabilization of wild-type p53 protein, we examined these tumors for MDM-2 amplification. None of the tumors with MDM-2 amplification exhibited p53 immunopositivity. Very weak p53 reactivity was detected in four malignant fibrous histiocytomas that had received either chemotherapy or radiotherapy. Of 16 metastatic lesions examined, only one contained a p53 mutation. In addition, for five cases in which both the original lesion and its metastases were analyzed, p53 alterations were not observed in the metastases if the tumor was wild-type at presentation. These data suggest that p53 alterations occur at different frequencies in various subtypes of sarcoma and, although detected in metastatic lesions, are not associated more frequently with progression.

Bone Neoplasms↗

Intraosseous malignant peripheral nerve sheath tumor. Report of a case and review of the literature.

We report a case of a malignant peripheral nerve sheath tumor arising in the distal femur of a 28-year-old man who had no stigmata of von Recklinghausen's disease. Roentgenograms and computed tomographic scans of the distal femur showed a single lytic intraosseous lesion with minimal soft tissue extension. Light microscopy demonstrated a tumor composed of spindle cells with myxoid areas. There was some nuclear pleomorphism and mitotic activity. The tumor cells were immunoreactive for S100 protein and neuron-specific enolase. Ultrastructurally, there were cells with long processes, which were focally invested by basal lamina. Some cells had numerous micropinocytotic vesicles. The tumor recurred in the femur 15 months following the initial curettage. Computed tomographic scan of the lungs at that time showed a nodule, which has since enlarged. Primary osseous malignant peripheral nerve sheath tumors are uncommon. A literature review revealed only 18 previous cases, the majority of which occurred in the mandible or maxilla. This is a rare case of intraosseous malignant peripheral nerve sheath tumor of a long bone, with both immunohistochemical and ultrastructural confirmation of nerve sheath differentiation.

Adult↗

Histological necrosis in soft tissue sarcoma following preoperative irradiation.

Forty-eight patients with soft tissue sarcomas that presented adverse features for treatment by limb salvage surgery and postoperative irradiation were treated by preoperative irradiation and surgery using a consistent protocol. Following resection, the extent of histological necrosis in the specimen was scored according to the criteria of Willet et al. Of the 48 cases, 16 (34%) demonstrated Grade 1 response (< 50% necrosis), 15 (31%) Grade 2 (50-80% necrosis), and 17 (35%) Grade 3 (> 80% necrosis). There was a trend toward more extensive necrosis in liposarcoma tumors (53% showing Grade 3 response compared to 26% of other sarcomas). Logistic regression analysis demonstrated a significant relationship between necrosis and tumor size (P < 0.001) with larger tumors having higher grades of necrosis. Tumor grade did not seem to affect the extent of necrosis. In comparison to the previous report of necrosis in soft tissue sarcoma following irradiation, the current analysis revealed a smaller proportion of tumors with Grade 3 necrosis.

Adult↗

Local control of soft tissue sarcoma of the extremity: the experience of a multidisciplinary sarcoma group with definitive surgery and radiotherapy.

Data gathered on 62 patients with soft tissue sarcoma of an extremity, treated in entirety by an experienced multidisciplinary sarcoma group, were analysed. With a philosophy of emphasising attainment of histologically negative margins at carefully planned limb sparing surgery, combined with either pre-operative or postoperative radiation therapy, a crude local control rate of 95% (59 of 62 patients) at a minimum of 24 months follow-up was obtained. Of 9 patients with microscopically positive margins after definitive surgery, 8 had undergone maximal resection compatible with preservation of function. One of these 9 failed locally, indicating that radiation therapy is effective in eradicating microscopic disease in this tumour. The excellent local control obtained with limb-sparing surgery in this series justifies early referral of patients with these uncommon cancers to an experienced multidisciplinary unit. 26 patients (42%) failed systemically at a minimum of 24 months follow-up, and 19 (30.6%) died of their disease, confirming the need for effective systemic therapy in soft tissue sarcoma. Tumours greater than 10 cm in diameter had a greater risk of systemic relapse.

Adolescent↗

Susceptibility to radiation-carcinogenesis and accumulation of chromosomal breakage in p53 deficient mice.

The p53 tumour suppressor gene is an important participant in the cellular response to ionizing radiation and other DNA damaging agents. Cells which lack p53 are unable to arrest cell cycle or enter into apoptotic cell death following irradiation. Moreover, these p53 deficient cells exhibit an increased resistance to DNA damaging agents, including radiation. The significance of this radiation-resistance and its relationship to the role that p53 plays in tumour suppression and the cellular radiation response has not yet been determined. In this report we have analyzed p53 deficient mice, expressing either a mutant p53 transgene or having a targeted p53 null allele, in order to investigate the role that p53 plays in governing susceptibility to radiation-carcinogenesis and in controlling the in vivo accumulation of chromosomal abnormalities. We show that wild-type p53 plays a critical role in controlling susceptibility to gamma-radiation-induced tumorigenesis, and sarcomas and lymphomas rapidly appear in irradiated p53 transgenic mice. Moreover, this susceptibility to radiation-carcinogenesis is associated with a two-fold increase in the in vivo accumulation of radiation-induced double stranded chromosomal breaks relative to that observed in wild-type animal. Taken together, these observations suggest that p53 acts to suppress tumour formation in vivo by preventing the accumulation of cells that have sustained radiation-induced DNA damage.

Animals↗

Are antibodies reactive with chondrocyte proteins enriched in synovial fluids of patients with rheumatoid arthritis?

In this study we examined the reactivity of synovial fluid (SF) antibodies (Abs) from patients with rheumatoid arthritis (RA) against chondrocyte proteins. The levels of IgG, IgM and IgA in the synovial fluids varied from patient to patient, but were similar to the levels found in each individual's serum. Although the Abs in SF and serum of RA patients reacted with several molecular weight classes of chondrocyte proteins, this reactivity was very low. Synovial fluid and serum Abs from the same patients reacted with similar chondrocyte proteins and to a similar extent, suggesting that the level of Abs reactive with chondrocyte proteins is not enriched in the SF. These data demonstrate that SF from RA patients contain high levels of Abs, however, there is very little reactivity with chondrocyte proteins beyond that observed in serum of normal and RA patients.

Animals↗

Schwannoma of the intrasternomastoid portion of the spinal accessory nerve: sophisticated pre-operative MRI diagnosis and appropriate surgical management.

In 1986, the authors reported the CT imaging findings which were specific for the diagnosis of schwannoma of the intrasternomastoid portion of the spinal accessory nerve. This successful imaging diagnosis led to appropriate surgical management with preservation of motor nerve function. In this manuscript, magnetic resonance imaging (MRI) was utilized to correctly diagnose the identical lesion, again with the same satisfactory surgical results. Both the CT and MRI findings are unique and specific, and the purpose of this short manuscript is to identify the MRI findings and link these to the previously recorded CT radiographic signs.

Accessory Nerve↗

Analysis of alterations in the retinoblastoma gene and tumor grade in bone and soft-tissue sarcomas.

We examined 43 sporadic bone and soft-tissue sarcomas for molecular genetic alterations affecting the retinoblastoma susceptibility gene Rb-1 (also known as RB1). The gene was altered in 6 of 14 sporadic osteosarcomas and in 5 of 29 other bone and soft-tissue sarcomas. Rb-1 messenger RNA (mRNA) transcripts were detected in normal tissues and benign lipomas, but they were absent or altered in each of the 19 sarcomas we examined. To examine the association of deletions in the Rb-1 gene with tumor grade, we correlated the DNA alterations in the Rb-1 gene with clinical data for 36 patients. The Rb-1 gene was altered in 40% of high-grade bone and soft-tissue tumors, but not in low-grade bone tumors and in only one low-grade, soft-tissue sarcoma. Overall, 10 of 25 high-grade sarcomas had detectable alterations of the Rb-1 gene compared with only 1 of 11 low-grade tumors.

Bone Neoplasms↗

Cutaneous and mucosal neoplasms in bone marrow transplant recipients.

Fifty-six long-term survivors of bone marrow allografts were followed for a minimum of 40 months after bone marrow transplantation (BMT) to determine the frequency of secondary malignancies. The 56 patients included ten with severe aplastic anemia (SAA), 16 with acute myeloblastic leukemia (AML), 11 with acute lymphoblastic leukemia (ALL), and 19 with chronic myelogenous leukemia (CML). All patients received a preparative regimen combining high-dose chemotherapy with total body irradiation (TBI). Three patients developed a malignancy of the skin or oral mucosa. Two were diagnosed as squamous cell carcinoma and one as a malignant melanoma. All three patients had chronic graft versus host disease (GvHD) and were treated for prolonged periods with immunosuppressive medications. The lesions of all patients developed in areas involved by chronic GvHD.

Adult↗

Fluoride treatment of postmenopausal osteoporosis: age, renal function, and other clinical factors in the osteogenic response.

We report on 61 women with postmenopausal osteoporosis who were treated with either plain sodium fluoride (NaF) capsules or enteric-coated NaF tablets for 4 years, in whom possible therapeutic and toxic effects were monitored. In these patients there was a mean increase in axial bone mineral mass, assessed by neutron activation analysis, of 26.2% +/- 2.4% (SEM) during the 4 years. This corresponds to a decrease in the bone deficit (compared with reference values) of 48.6%. The response was linear over 4 years. The main predictors of the osteogenic response were bone fluoride (r = 0.52, p less than 0.01), serum fluoride (r = 0.50, p less than 0.01), and age (0.39, p less than 0.01). Patients over 65 years of age achieved higher bone fluoride (F) levels and a significantly greater increase in bone mineral than younger patients (32.8 vs. 17.9%, p less than 0.01), associated with an age-related decline in renal function; serum fluoride was significantly and negatively correlated to creatinine clearance (r = -0.52, p less than 0.01). Although the effect of NaF on fracture rate could not be assessed in this uncontrolled study, the major factors associated with the occurrence of new vertebral fractures were the number of vertebral fractures and the bone mineral mass at the beginning of therapy. There was no correlation between vertebral fracture rate and serum or bone fluoride or other parameters of the osteogenic response, but patients who did not experience new vertebral fractures achieved a normal bone mineral content sooner than those who had new fractures during therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

The effect of fluoride on bone histology in postmenopausal osteoporosis depends on adequate fluoride absorption and retention.

Forty-one women with idiopathic postmenopausal osteoporosis have been followed for 2 years after initiation of sodium fluoride at 40-50 mg/day, given together with a daily calcium supplement of 1 gram and vitamin D2, at 50,000 IU weekly. Histological and histomorphometric analyses were done on bone biopsies taken prior to and after 1 year of treatment (mean 1.25 +/- 0.35 years). Thirty patients (74%) developed the histological fluoride effect of hyperosteoidosis, while the remaining 11 patients (26%) had no change from pretreatment biopsies. Hyperosteoidosis was based on increased values for osteoid volume and/or thickened osteoid with greater than 3 lamellar bands. Based on previously reported findings, this histological evidence of hypersoteoidosis within 12-18 months of initiation of therapy provides a useful predictor of ultimate satisfactory fluoride response in terms of bone mineral accretion. No increases in bone mass (measured by neutron activation analysis) were observed at the time of the posttreatment biopsy but, according to this previous work, increases are anticipated over a further 2-3 years of treatment. Factors affecting the development of hyperosteoidosis were analyzed. Hyperosteoidosis was associated with a significantly higher dose of sodium fluoride and a significantly higher level of bone fluoride retention but without significant increase in fasting serum fluoride. Results suggest that fluoride retention depends not only on fluoride dose but also on body size, renal function, and intestinal absorptions of calcium and fluoride. There were no differences in the initial investigations between patients with and without hyperosteoidosis, with respect to age, years of postmenopause, estrogen use, initial biochemistry, or initial bone histology.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗