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Biomedical subjects

E C Halperin

Publications and source records attributed to E C Halperin.

At least 19 recordsLinked to original sources
PubMed1998

Toxicity, pharmacology and feasibility of administration of PEG-L-asparaginase as consolidation therapy in patients undergoing bone marrow transplantation for acute lymphoblastic leukemia.

We attempted to administer PEG-L-asparaginase (PEG-L-A) following hematologic recovery to 38 patients undergoing autologous or allogeneic marrow transplantation for acute lymphoblastic leukemia (ALL). Twenty-four patients (12 of 22 receiving allogeneic and 12 of 16 receiving autologous transplants) received between one and 12 doses of PEG-L-A, including nine who completed the planned 12 doses of therapy. The toxicities encountered were similar to those observed in non-transplanted patients undergoing therapy with PEG-L-A and included allergic reactions, pancreatitis, weight loss, hypoalbuminemia, and low levels of anti-thrombin III. Of the 24 who received the drug, eight remain in remission. Of 12 patients in second remission at the time of transplantation who received PEG-L-A, five of seven who received allogeneic and two of five who received autologous transplants remain in remission, 16+ to 46+ months from transplant. While PEG-L-A could be administered to most of the patients undergoing marrow transplantation for ALL, most patients either relapsed while receiving the drug or developed toxicities which resulted in abbreviated courses. At this time, we cannot recommend PEG-L-A as single agent, post-BMT chemotherapy.

Adolescent↗
PubMed1997

Event-free survival of children with biologically favourable neuroblastoma based on the degree of initial tumour resection: results from the Pediatric Oncology Group.

We analysed the 2-year event-free survival (EFS) of 49 patients 1 year of age and older, with stage 2B or 3 neuroblastoma, treated on Pediatric Oncology Group protocols 8742 and 9244, with respect to the degree of tumour resection at diagnosis. The 2-year EFS rate for 21 children whose tumours were completely resected at diagnosis was 85% (SE = 10%) compared with an EFS rate of 70% (SE = 9%) for the 28 children whose tumours were incompletely resected at diagnosis. Despite the observed trend in favour of complete resection, these EFS curves were not statistically significantly different (P = 0.259). Patients with favourable Shimada histology tumours had an EFS rate of 92% (SE = 7%) compared with a rate of 58% (SE = 15%) for patients with unfavourable histology tumours. EFS curves for the two histologic groups were significantly different (P = 0.009). The impact of aggressive surgery and adjuvant chemotherapy on the outcome of patients with biologically favourable regional neuroblastoma is still unclear.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Are there sex biases in standardized tests of radiation oncology knowledge?

PURPOSE/OBJECTIVE: Recent studies have identified biases directed against women in standardized tests. We tested for the existence of such biases in the American College of Radiology (ACR) In-Training Examination in Radiation Oncology and the American Board of Radiology (ABR) Written Radiation Oncology Board Examination. MATERIALS AND METHODS: Our request to the ABR to permit us to study performance on their examinations, as a function of sex, was refused. We obtained scores, through the cooperation of six academic radiation oncology departments, for residents-in-training taking the in-service examination and candidates taking the written board examination for the first time. Test results for 1984 to 1995 were blinded as to name, but not sex or institution of training. For the in-service examination, scores are reported as percentiles normalized to the year of training. The effect of multiple scores for the same resident was assessed using a repeated-measures analysis of variance. Residents were nested within each sex/institution combination and crossed with training year and calendar year. The effects of three factors (sex, institution, and year the examination was taken) on the results of the biology, physics, and clinical sections were evaluated with an analysis of variance. The interactions of sex with institution and year were included to determine the scope of the sex effect. For the board examination, scores are reported as percentiles, as well as an overall pass/ fail outcome. An analyses of variance was performed similar to that used for the in-service examination. In addition, Fisher's exact test and logistic regression were used to analyze overall outcome (pass/fail). RESULTS: We obtained data for 79 residents (48 men and 31 women, 1.54:1) who took the in-service examinations 165 times. Sixty-two residents (41 men and 21 women, 1.95:1) had an initial sitting for the ABR written examination. On the in-service examination, for the biology, physics, and clinical subsections, calendar year, training year, and sex did not have a significant effect on examinees scores. Institution of training had a significant effect (P < .02) on the scores in biology and physics. The total in-service examination scores were not significantly influenced by calendar year, training year, or sex. Institution of training has a strong influence on overall score (P = .03) and the interaction of sex with training year is near significance level (P = .06). The power for our statistical tests ranged from 0.88 to 0.99. On the board examination, sex, institution of training, year the examination was taken, and interaction of sex with year or sex with institution of training did not have a significant effect on test scores. Pass rates were 90% for men versus 81% for women (P = .43). CONCLUSION: Sex did not significantly influence the results of the in-service examination or the written board examination. Institution of training is the strongest influence on the results of the in-service examination.

Adult↗
PubMed1996

Is there a correlation between duration of presenting symptoms and stage of medulloblastoma at the time of diagnosis?

BACKGROUND: Does a "delay in diagnosis" lead to a child being diagnosed with advanced stage as opposed to early stage medulloblastoma? Correlation between the duration of a patient's presenting symptoms and stage at diagnosis was examined. METHODS: The population consisted of 72 consecutive patients with histologically proven medulloblastoma diagnosed between July 1, 1983 and July 31, 1995. A standard history and physical examination format was used to record the nature and duration of presenting symptoms. Patients were staged by use of the operative findings, pre- and postoperative cranial computed tomography (CT) scans and, later in the series, cranial magnetic resonance imaging (MRI) studies and, for determination of the M stage, myelography, spinal MRI, and postoperative cerebrospinal fluid cytology. RESULTS: There were 40 males (56%) and 32 females (44%) with a mean age of 11.8 years. The most common presenting symptoms were vomiting (67%), headache (60%), ataxia (40%), and nausea (39%). By the Chang-Harisiadis (CH) system, 39 patients (54%) were found to have high stage medulloblastoma (T3b-4M0 or any TM1-4), 27 (38%) had low stage disease (T1-3aM0), and in 6 (8%) the stage could not be fully determined. By the Langston modification of the Change-Harisiadis system (LCH) 38 patients (54%) had high stage, 24 (32%) had low stage, and in 10 (14%) the stage could not be fully determined. Fifty of the 66 patients for whom the duration of symptoms was known (76%) had < or = 3 months of symptoms prior to stage. High CH stage patients had a mean duration of symptoms of 7.4 +/- 6.9 weeks versus 19.5 +/- 22.5 weeks for low stage patients. (P < 0.001). High LCH stage patients had a mean duration of symptoms of 7 +/- 6.6 weeks versus 15.4 +/- 16.4 weeks for low stage patients (P < 0.01). Patients ultimately found to have MO disease were diagnosed more slowly (16.1 +/- 20 weeks) than those with M1 (7.3 +/- 5.3 weeks), M2 (6 +/- 5.3 weeks), or M3 disease (6.8 +/- 5.9 weeks) M0 vs. M1-3, P < 0.02). No patients had M4 disease. Using an alternative definition of high versus low stage (T4M0 or any TM1-4 vs. T1-3bM0) currently under consideration by pediatric oncologists, the duration of symptoms remained significantly longer for low stage disease in the CH system (high vs. low, 7.2 +/- 5.8 weeks vs. 17.5 +/- 19.1 weeks, P < 0.01) but not in the LH system (high vs. low, 10.6 +/- 16.1 weeks vs. 13.9 +/- 15.9 weeks, P not significant). CONCLUSIONS: A short duration of symptoms is associated with the diagnosis of more advanced medulloblastoma. This finding has significant potential implications for the identification of prognostic groups in medulloblastoma as well as medical-legal claims of "delay in diagnosis" and capitated health care issues.

Cerebellar Neoplasms↗
PubMed1996

Impact of radiation technique upon the outcome of treatment for medulloblastoma.

Craniospinal irradiation (CSI) is an essential component of the therapy of medulloblastoma. Because medulloblastoma disseminates via the cerebrospinal fluid (CSF), CSI technique involves the irradiation of all CSF-bearing areas which are at risk for tumor seeding. Underdosing with radiation because of inadequacies in CSI technique will produce dose "cold spots" which have the potential of serving as a nidus for tumor recurrence. A simple mathematic model of subclinical disease in medulloblastoma based on the available data concerning the radiosensitivity of medulloblastoma cell lines as well as the known clinical dose-response relationships support the hypothesis that for most cases of medulloblastoma, the radiotherapist is working in a range of doses arrayed on the steep portion of the tumor control probability curve. Underdosing of CSF-bearing areas because of technical problems at the junction of the cranial and spinal fields of irradiation, placement of shielding blocks in the cribiform plate-subfrontal region, and/or anatomic errors in the design of the caudal end of the CSI fields may lead to significant risks of tumor relapse. One may debate the necessity of a posterior fossa boost encompassing the entire anatomic posterior fossa rather than the primary tumor volume with a margin. This review critically evaluates the potential impact of CSI technique upon the outcome of treatment for medulloblastoma, and suggests future areas of inquiry.

Cerebellar Neoplasms↗
PubMed1996

Placental blood as a source of hematopoietic stem cells for transplantation into unrelated recipients.

BACKGROUND: Transplantation of bone marrow from unrelated donors is limited by a lack of HLA-matched donors and the risk of graft-versus-host disease (GVHD). Placental blood from sibling donors can reconstitute hematopoiesis. We report preliminary results of transplantation using partially HLA-mismatched placental blood from unrelated donors. METHODS: Twenty-five consecutive patients, primarily children, with a variety of malignant and non-malignant conditions received placental blood from unrelated donors and were evaluated for hematologic and immunologic reconstitution and GVHD. HLA matching was performed before transplantation by serologic typing for class I HLA antigens and low-resolution molecular typing for class II HLA alleles. In donor-recipient pairs who differed by no more than one HLA antigen or allele, high-resolution class II HLA typing was done retrospectively. Fordonor-recipient pairs who were mismatched for two HLA antigens or alleles, high-resolution typing was used prospectively to select the best match for HLA-DRB1. RESULTS: Twenty-four of the 25 donor-recipient pairs were discordant for one to three HLA antigens. In 23 of the 25 transplant recipients, the infused hematopoletic stem cells engrafted. Acute grade III GVHD occurred in 2 of the 21 patients who could be evaluated, and 2 patients had chronic GVHD. In vitro proliferative responses of T cells and B cells to plant mitogens were detected 60 days after transplantation. With a median follow-up of 12 1/2 months and a minimal follow-up of 100 days, the overall 100-day survival rate among these patients was 64 percent, and the overall event-free survival was 48 percent. CONCLUSIONS: HLA-mismatched placental blood from unrelated donors is an alternative source of stem cells for hematopoietic reconstitution in children.

Adolescent↗
PubMed1996

A phase III randomized prospective trial of external beam radiotherapy, mitomycin C, carmustine, and 6-mercaptopurine for the treatment of adults with anaplastic glioma of the brain. CNS Cancer Consortium.

PURPOSE: This study was designed to evaluate strategies to overcome the resistance of anaplastic gliomas of the brain to external beam radiotherapy (ERT) plus carmustine (BCNU). Patients were > or = 15 years of age, had a histologic diagnosis of malignant glioma, and a Karnofsky performance status (KPS) > or = 60%. METHODS AND MATERIALS: In Randomization 1, patients were assigned to receive either ERT alone (61.2 Gy) or ERT plus mitomycin C (Mito, IV 12.5 mg/m(2)) during the first and fourth week of ERT. After this treatment, patients went on to Randomization 2, where they were assigned to receive either BCNU (i.v. 200 mg/m(2)) given at 6-week intervals or 6-mercaptopurine (6- MP, 750 mg/m(2) IV daily for 3 days every six weeks), with BCNU given on the third day of the 6-MP treatment. Three hundred twenty-seven patients underwent Randomization 1. One hundred sixty-four received ERT alone, and 163 received ERT + Mito [average 52.7 years; 63% male; 69% glioblastoma multiforme (GBM); 66% had a resection; 56% KPS > or = 90%]. Step-wise analysis of survival from Randomization 1 or 2 indicates that survival was significantly diminished by: (a) age > or = 45 years (b) KPS < 90%; (c) GBM/gliosarcoma histology; (d) stereotactic biopsy as opposed to open biopsy or resection. Median survival from Randomization 1 in both arms (ERT + Mito) was 10.8 months. Median survival from Randomization 2 was 9.3 months for BCNU/6MP vs. 11.4 months for the BCNU group (p = 0.35). Carmustine/6-MP showed a possible survival benefit for histologies other than GBM/GS. Two hundred and thirty-three patients underwent Randomization 2. The proportion of patients in the ERT group who terminated study prior to Randomization 2 was significantly less in the ERT group than in the ERT + Mito group (20 vs. 37%, p < 0.001). CONCLUSIONS: (a) The addition of Mito to ERT had no impact on survival; (b) patients treated with ERT + Mito were at greater risk of terminating therapy prior to Randomization 2; (c) there was not a significant survival benefit to the addition of 6-MP to BCNU.

Adult↗
PubMed1996

Long-term results of therapy for stage C neuroblastoma.

BACKGROUND: The appropriate therapy for Stage C neuroblastoma (NB) is uncertain. Because of the need for information applicable to the development of new randomized trials, we deemed it appropriate to investigate the patient characteristics, survival, patterns of failure, and complications of therapy in these children. METHODS: Search of the medical records of Duke University Medical Center from 1/1/60 to 3/1/95 disclosed 146 patients with NB, which included 13 Stage C patients. RESULTS: Mean age at diagnosis was 3.6 years. Twelve patients had primary abdominal tumors (92%) and one had a thoracic primary (8%). Twelve (92%) of the patients received chemotherapy including cyclophosphamide. 11 (85%). Adriamycin, 6 (46%), cisplatinum, 4 (30%), and VP 16, 4 (30%). All patients received radiotherapy (RT, mean dose administered 22.6 +/- 8 Gy). With a mean follow-up of 8 years, the 10-year overall survival was 54% and the relapse-free survival was 46%. Four patients relapsed in the primary operative tumor bed and primary RT field, two relapsed in mediastinal or left supraclavicular lymph nodes as well as distantly following treatment of upper abdominal primaries, and in one the site of relapse is unknown. Long-term complications of therapy included two children who developed secondary malignancies associated with RT, two girls who developed primary ovarian failure, five children with clinically significant kyphosis and scoliosis, and one who suffered postoperative wound dehiscence following RT. CONCLUSIONS: Although this study did not include modern techniques of staging with n-myc amplification and DNA index, the occurrence of next echelon nodal failures gives credence to the continuation of the dialogue concerning the appropriate role of "prophylactic" irradiation to mediastinal and left supraclavicular nodes in locally advanced upper abdominal NB. Documentation of significant long-term ill effects reinforces the need to critically evaluate the indications for RT.

Abdominal Neoplasms↗
PubMed1996

Fabrication and testing of a device capable of reducing the incidence of ventricular shunt promoted metastasis.

PURPOSE/OBJECTIVE: Some malignant brain tumors shed cells into the cerebrospinal fluid (CSF). These tumors may implant throughout the neuroaxis via the CSF. With the placement of a ventriculoperitoneal (VP) or ventriculoatrial (VA) shunt, tumor cells free-floating in the CSF may be carried through the shunt to the remainder of the body. Mechanical filtration devices to prevent this are not reliable. We report the development of a new device capable of reducing the incidence of shunt promoted metastasis. MATERIALS & METHODS: The device exposes the draining CSF, as it passes through a baffle system, to a localized high-intensity radiation field adequately shielded from surrounding normal tissue. The prototype consists of geometrically fixed iodine-125 (125I) sources. The device accommodates the maximum CSF flow rate of 500 ml/24 hours. Radiation exposure to clonogenic cells occurs as they transit through the baffle system. Since the volume of the prototype device is 14 ml, a tumor cell floating through the device will be exposed to radiation for 40 minutes. Utilizing the human medulloblastoma cell line D425 MED, a limiting dilution clonogenic assay was performed. Suspensions of tumor cells in liquid medium were pumped through the device at the maximum anticipated CSF production rate of 0.35 ml/min. After the cells, with their tissue culture medium, were received from the device, a series of nine 5-fold dilutions were prepared from the suspensions which initially contained 10(6) tumor cell/ml. Plates were then incubated and growth was demonstrated by visual scoring of colonies of more than 20 cells. Limiting dilution data analysis was performed. Radiation surveys of the fully loaded (approximately 1.8 Ci) 125I prototype were conducted. A well calibrator was used to measure the activity of the fully loaded device. RESULTS: When the device was loaded with 125I seeds providing a dose of 364-479 cGy the probability of clonogen survival was 0.033. Radiation exposure levels at the exterior surface of the shielded device were in the range of 2-5 mR/hr and thus fell within guidelines for acceptable normal tissue exposure. Attenuation of radiation by the shielding case for the fully loaded device was 10(-5). CONCLUSION: The device kills medulloblastoma cells as they are pumped through it. If the risk of metastasis is linearly related to the number of clonogenic cells, then the device would, we infer, reduce the risk of shunt-born metastasis by a factor of 0.033 and merits further investigation.

Brain Neoplasms↗
PubMed1996

Resolution of Budd-Chiari syndrome following bone marrow transplantation for paroxysmal nocturnal haemoglobinuria.

Thrombosis of the hepatic veins (Budd-Chiari syndrome) is a life-threatening thrombotic complication which can occur in patients with paroxysmal nocturnal haemoglobinuria (PNH). Despite aggressive medical and surgical therapy, mortality from Budd-Chiari syndrome remains high. We report a boy with PNH who developed Budd-Chiari syndrome and underwent syngeneic bone marrow transplantation (BMT). Now, 3 years following BMT, he has had dramatic clinical and radiographic evidence of resolution of the thrombosis. We suggest that BMT for PNH can successfully correct life-threatening thrombosis in patients with PNH.

Bone Marrow Transplantation↗
PubMed1996

New and recurrent tumors in germinal retinoblastoma: is there a treatment effect?

Patients with germinal retinoblastoma (those with bilateral disease or positive family history) have a mutation which puts them at risk for developing new tumors. It is unclear whether the frequency of new tumor development is effected by the type of treatment employed. It may be hypothesized that external beam radiation "sterilizes' the whole retina, and thus decreases the risk of new and recurrent tumors. We reviewed our experience with 66 eyes in 47 patients over the past ten years. We did not find a significant difference in the incidence of new and recurrent retinoblastoma among eyes treated with external beam radiation versus focal modalities.

Brachytherapy↗
PubMed1995

Recipient Kupffer cell influx into xenografted liver.

Previously we reported that the combination of total lymphoid irradiation (TLI), cyclosporine A (CsA), and splenectomy have an immunosuppressive effect sufficient to significantly prolong liver xenograft survival in the LVG hamster to the LEW rat model. Using this model, we have investigated recipient Kupffer cell influx into the xenografted liver. In the rat liver, the Kupffer cells are heavily stained with Ki-M2R, a rat anti-macrophage monoclonal antibody, whereas sinus endothelial cells and liver parenchymal cells are invariably negative. Kupffer cells of the hamster liver are not stained with Ki-M2R. In the xenografted animals, we found cells in the sinusoidal wall of the xenograft stained, with progressively increased activity, in animals 45-60 days after transplant. The morphological pattern of these Ki-M2R-positive cells in the hepatic xenograft resembled the Kupffer cells of the normal rat liver. These findings indicate recipient macrophage influx into the xenografted liver.

Animals↗
PubMed1995

What medical schools and universities can learn from one another.

Colleges and universities devoted to undergraduate education and non-medical graduate education (hereafter called "universities") have much to teach medical schools and much to learn from them. Universities and medical schools differ significantly in their sources of revenue, cultures of promotion and tenure, academic values, and decision-making processes. Yet from the experience of universities, medical schools can learn innovative techniques of curriculum assessment and teaching, how to handle diversity issues, and ways to expand the definition of scholarship. In turn, medical schools can help teach universities the importance of fiscal and regulatory accountability, the benefits of interdisciplinary efforts, the practical benefits of problem-based learning, and techniques for adjusting to rapid change. The authors, all with medical school faculty backgrounds, developed the views reported in this article when they were Fellows in a leadership training program sponsored by the American Council on Education (ACE). They urge their colleagues to reach out beyond their specialties and departments and learn from higher education institutions that are grappling with problems analogous to those faced by medical schools.

Schools, Medical↗
PubMed1995

Is tenure irrelevant for academic clinicians?

Academic tenure is the guarantee that a faculty member cannot be arbitrarily dismissed. The tenure system developed to maintain academics free of external pressure and coercion, and in dramatic instances tenure has been used to defend academic freedom. With the development of the research-oriented medical school staffed by full-time faculty, the reward system of tenure and promotion was grafted on to academic medicine. The changing face of academic clinical medicine places significant stresses on the traditional tenure system and raises the question of whether it is fundamentally irrelevant. Tenure has been defended as the protector of free inquiry, insurer of academic excellence, contributor to research and its benefits to society, and a means of selecting the best and brightest for our faculties. Tenure has been criticized as a contributor to academic sloth, codifier of gender and racial discrimination, and as a system unable to deal with the economic realities of high-priced referral specialties. As academic medical centers increase their efforts at clinical outreach, it is unclear whether traditional promotion and tenure will be of interest to clinicians employed solely to deliver primary care. In this special report, I review the history of tenure, arguments for and against its use for clinicians, and proposals for reform.

Academic Medical Centers↗