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Biomedical subjects

J Healey

Publications and source records attributed to J Healey.

At least 19 recordsLinked to original sources
PubMed1997

p53 and MDM2 alterations in osteosarcomas: correlation with clinicopathologic features and proliferative rate.

BACKGROUND: Alterations of the p53 gene and of MDM2, a gene coding for a p53 binding protein, have been implicated in the pathogenesis of osteosarcoma (OS). METHODS: To determine the frequency of alterations of the p53/MDM2 pathway in OS and their possible correlation with clinicopathologic features, MDM2 copy number and p53 protein levels were determined in a series of 83 samples of OS by quantitative Southern blot analysis and immunohistochemistry, respectively. RESULTS: Positivity for p53 was found in 26.5% and MDM2 amplification in 6.6% of the samples analyzed in a mutually exclusive fashion with one exception. Overall, alterations of the p53/MDM2 pathway occurred in 34% of cases; p53 accumulation was not associated with a higher proliferative rate. The mean age of patients with p53 positive OS (40 years) was older than that of the p53 negative group (28 years) (P < 0.04). Furthermore, three of the four cases of OS arising in Paget's disease showed p53 accumulation. CONCLUSIONS: Alterations of the p53/MDM2 pathway are frequent in OS and usually represent mutually exclusive tumorigenic events. p53 does not appear to be a major determinant of proliferative rate in OS.

Adult↗
PubMed1995

Correlation of the findings of thallium-201 chloride scans with those of other imaging modalities and histology following therapy in patients with bone and soft tissue sarcomas.

We performed a retrospective [corrected] study to evaluate the imaging potential of thallium-201 as compared with other imaging modalities in differentiating residual/recurrent tumors from post-therapy changes in patients with musculoskeletal sarcomas. 201Tl scans, magnetic resonance imaging (17), X-ray computed tomography (6) or contrast angiography (6) studies in 29 patients previously treated for musculoskeletal sarcomas were correlated with either histopathologic findings (26 patients) or 2-year clinical follow-up (three patients). All imaging studies were acquired within 2 weeks. Ratios of 201Tl tumor uptake to the contralateral (28 patients) or adjacent region of interest were calculated. When qualitative interpretation was in doubt, only those cases with a ratio of 1.5 or more were considered suggestive of recurrent of residual viable tumor tissue. Residual or recurrent tumor tissue was verified in 21 patients by biopsy. All had true-positive 201Tl scans while the other imaging modalities were true-positive in 20 and equivocal in one. In eight patients, there was no evidence of viable tumor tissue as proven by biopsy in five and long-term clinical follow-up in three. 201Tl scan was false-positive (ratio 1.5) in one patient and true-negative in seven while the other imaging modalities had four false-positives. The average 201Tl ratios were 2.8+/-1.1 in the true-positive cases and 1.3+/-0.3 in the true-negative cases. The percentage sensitivities, specificities, and accuracy for 201Tl were 100%, 87.5%, and 96.5% versus 95%, 50%, and 82.7% respectively for other imaging modalities. These results indicate that 201Tl scintigraphy is more accurate than other imaging modalities in differentiating residual/recurrent musculoskeletal sarcomas from post-therapy changes.

Adolescent↗
PubMed1994

Intraosseous hemangioma of the talus: a case report.

A 35-year-old female patient presented to us with a lesion in the talus that on AP-roentgenographic view simulated an osteoid osteoma. Final pathology revealed it to be an intraosseous hemangioma. An intraosseous hemangioma at this site is extremely uncommon and has not been previously reported.

Adult↗
PubMed1994

Treatment of a second bone osteosarcoma. 3 cases and an unusual MRI finding.

We report 3 patients with a second bone involved with osteosarcoma. They were found among approximately 200 cases of limb-sparing surgery with chemotherapy. 1 patient had the unusual finding of a positive MRI scan with all other routine tests negative. The first and then the second bone tumor were successfully removed with limb-sparing surgery. All 3 patients are doing well, with no evidence of disease.

Adolescent↗
PubMed1992

The relationship between thallium uptake, blood flow, and blood pool activity in bone and soft tissue tumors.

Twenty patients with known primary untreated and recurrent bone and soft tissue tumors underwent thallium imaging and three-phase bone imaging in the same session. The ratio of thallium uptake in the tumor tissue to the contralateral normal tissue areas was compared with the same ratio for phase 1 (blood flow or arterial phase), phase 2 (blood pool), and phase 3 (delayed medroxy-diphosphonate, MDP, uptake). There was poor correlation between Tl uptake and phases 1 and 3 of the bone scan ratios; r = 0.37 and 0.46; P = 0.097 and 0.047, respectively. The thallium uptake ratios correlated well with blood pool ratios (phase 2) (r = 0.84 and P less than 0.01). In contrast to uptake into normal muscle, Tl-201 uptake into tumor is not highly dependent on blood flow alone and other factors predominate in determining its magnitude.

Bone Neoplasms↗
PubMed1992

Chemotherapy for nonmetastatic osteogenic sarcoma: the Memorial Sloan-Kettering experience.

PURPOSE: Adjuvant chemotherapy improves disease-free survival (DFS) for patients with osteogenic sarcoma (OS). We reviewed our experience with OS to determine prognostic factors, the role of preoperative chemotherapy and subsequent histologic response, and the role of salvage chemotherapy after poor initial response. METHODS: From 1975 to 1984, we saw 279 patients with previously untreated OS without metastasis. All patients received intensive chemotherapy and underwent surgical resection of primary tumor. Chemotherapy included high-dose methotrexate; Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH); and bleomycin, cyclophosphamide, and dactinomycin (BCD). Selected patients also received cisplatin. RESULTS: DFS was not affected by use of preoperative chemotherapy versus immediate surgery, by use of limb-sparing surgery versus amputation, age, sex, or dose intensity of chemotherapy. DFS did correlate with serum lactate dehydrogenase (LDH), alkaline phosphatase, primary tumor site, race, and histologic response to preoperative chemotherapy. There was no difference in DFS for patients with a poor histologic response who did or did not receive cisplatin, although patients who did receive cisplatin had a longer time to relapse. The 5-year DFS was 76% for patients aged less than or equal to 21 years who had extremity primary tumor and were treated with the T10 protocol. CONCLUSIONS: Intensive chemotherapy can achieve DFS for a high proportion of patients with OS. Although it is a powerful predictor of DFS, histologic response to preoperative chemotherapy cannot be assessed at diagnosis. We have not shown an ability to salvage patients with an unfavorable response. We need to increase the proportion of patients with a favorable response, identify the patients who will have an unfavorable response, and develop novel treatments to salvage poor responders.

Adolescent↗
PubMed1991

Osteoid osteoma. Diagnosis, localization, and treatment.

The preoperative insertion of a needle under computed tomographic scan, performed under local anesthesia, is a convenient and important new way to localize the nidus in osteoid osteoma. It necessitates less bone removal, which should reduce the postoperative fracture rate. It should also help to locate the lesion during surgery. Some clinical points and previously unstressed pathologic findings are also discussed.

Aspirin↗
PubMed1990

Mechanism of synergistic induction of hepatic heme oxygenase by glutethimide and iron: studies in cultured chick embryo liver cells.

Heme oxygenase, the rate controlling enzyme for heme catabolism, is inducible by a variety of treatments, some of which induce by a heme-dependent mechanism and others by a heme-independent mechanism. This work shows that, in cultured chick embryo liver cells, synergistic induction of heme oxygenase by iron, added with the phenobarbital-like drug, glutethimide was heme-dependent. Addition of an inhibitor of heme biosynthesis abolished the synergistic induction of heme oxygenase providing evidence for the heme-dependent mechanism of induction. Glutethimide and iron appeared to induce at the transcriptional level since both heme oxygenase mRNA and protein levels correlate with changes in heme oxygenase activity.

Animals↗
PubMed1990

ECG evidence of limited myocardial infarction following coronary occlusion treated by early intravenous rt-PA infusion.

Serial 12-lead surface electrocardiograms (ECGs) were analysed in 110 patients with first evolving myocardial infarction entered in a double-blind placebo-controlled trial of intravenous rt-PA within 2.5 h (mean 1.9 +/- 0.5 (SD)) of pain onset. ECG analysis was performed by two 'blinded' analysts. QRS scoring (by the modified Selvester method) was used as an index of myocardial necrosis. Patient results were analysed according to infarct location. There was no difference between the two treatment groups in ST-segment elevation or QRS score at entry or up to 24 h after symptom onset. However from 24 h, QRS score was lower in patients with anterior infarction given rt-PA than in those given placebo: 5.4 +/- 2.8 vs 7.7 +/- 4.1 (P = 0.02) at 48 h; 4.7 +/- 3.2 vs 8.0 +/- 4.0 (P = 0.01) at 4-10 days; and 4.6 +/- 3.9 vs 7.5 +/- 3.9 (P = 0.01) at 21 days. For patients with inferior infarction, rt-PA treatment also resulted in a lower QRS score although this was not significantly different from the score of the placebo group (P = 0.07). Comparison of QRS scores with ejection fraction measured from the contrast ventriculogram taken at 21 days showed a moderate correlation (r = 0.46) in patients with anterior infarction but a poor correlation in patients with inferior infarction. These ECG results indicate that in evolving anterior myocardial infarction, there is limitation of infarct size from early rt-PA infusion.

Double-Blind Method↗
PubMed1989

Immunochemical detection of different isoenzymes of cytochrome P-450 induced in chick hepatocyte cultures.

This study investigated whether the same cytochrome P-450 (P-450) isoenzymes were inducible in cultures of chick-embryo hepatocytes as in the liver of chicken embryos. We purified two isoenzymes of cytochrome P-450 from the livers of 17-day-old-chick embryos: one of molecular mass approx. 50 kDa induced in vivo by the phenobarbital-like inducer glutethimide, and the second of approx. 57 kDa induced by 3-methylcholanthrene. Rabbit antiserum against the 50 kDa protein inhibited benzphetamine demethylase activity in hepatic microsomes (microsomal fractions) from glutethimide-treated chick embryo. Antiserum to the 57 kDa protein inhibited ethoxyresorufin de-ethylase activity in hepatic microsomes from methylcholanthrene-treated chick embryo. Cultured chick hepatocytes were treated with chemicals known to induce isoenzymes of P-450 in rodent liver. The induced P-450s were quantified spectrophotometrically and characterized by immunoblotting and enzyme assays. From these studies, chemical inducers were classified into three groups: (i) chemicals that induced a P-450 isoenzyme of 50 kDa and increased benzphetamine demethylase activity: glutethimide, phenobarbital, metyrapone, mephenytoin, ethanol, isopentanol, isobutanol, lindane, lysodren; (ii) chemicals that induced a P-450 isoenzyme of 57 kDa and increased ethoxyresorufin de-ethylase activity: 3-methylcholanthrene and 3,3',4,4'-tetrachlorobiphenyl; and (iii) the mono-alpha-substituted 2,3',4,4',5-pentabromobiphenyl, which induced both proteins and both activities. The immunochemical data showed that chick-embryo hepatocytes in culture retain the inducibility of glutethimide- and methylcholanthrene-induced isoenzymes of P-450 that are inducible in the liver of the chicken embryo.

Animals↗
PubMed1984

'The hidden society': the practical use of multi-dimensional scaling to illuminate the pattern of relationships between long-stay psychiatric residents.

This paper briefly reports testing the use of multi-dimensional scaling as a method to illuminate the complex pattern of relationships existing between patients in a long-stay psychiatric setting. The results did not support the hypothesis that recently formed rehabilitation groups in the hostel would serve to explain the pattern of relationships between patients. The results did, however, promote a more informed discussion regarding the origin and implications of patient relationships in long-stay psychiatric care, which served to revise staff ideas and options regarding the organization of care. Relationships between long-stay disabled psychiatric patients are notoriously opaque to observers. The use of multi-dimensional scaling helped make them more transparent.

Choice Behavior↗
PubMed1984

Development of motor co-ordination by normal left-handed children.

Ninety-six normal left-handed children were tested for motor co-ordination on a series of timed repetitive tasks, alternating left and right hands, feet and fingers. Preferred hand advantage could be demonstrated to the same degree for the left hand of these children as it had been for the preferred right hand in previously studied groups of the same age (Denckla 1973, 1974). The only test (finger to thumb successive opposition) that failed to show a preferred hand advantage in left-handers also had failed to show such an advantage among right-handers. This same test was performed more rapidly by left-handed girls than boys, as it had been by right-handed girls. However, left-foot superiority appeared to be less well established among left-handers than superiority of the right foot among right-handers, and at a later age. Left-handed children were less likely than their right-handed counterparts to choose their preferred hand when trying out a new task. Writing posture, i.e. whether inverted or straight, could not be established unambiguously for the left-handed children up to the age of 10, and often differed for writing and printing.

Child↗