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Biomedical subjects

Mark Bernstein

Publications and source records attributed to Mark Bernstein.

At least 37 records · Page 2Linked to original sources
PubMed2005

Postoperative recovery of complete sudden paraplegia due to lumbar schwannoma. Case report.

The authors present a rare case of acute complete paraplegia due to a lumbar schwannoma. The clinical presentation, magnetic resonance imaging features, and management strategy are discussed. A 29 year-old man presented with acute complete paraplegia and bladder and bowel incontinence. He had a history of stable back pain and a 4-year history of lower-extremity numbness bilaterally. Magnetic resonance imaging revealed an enhancing extraaxial mass filling the spinal canal over two segments below the conus medullaris. An L1-3 laminectomy was performed and the tumor was completely removed. Pathological evaluation showed features characteristic of a schwannoma. The patient regained almost complete motor function after 6 months. To the authors' knowledge, this is the first reported case of acute complete paraplegia secondary to lumbar schwannoma. Possible mechanisms of this occurrence are discussed.

Acute Disease↗
PubMed2004

SARS and hospital priority setting: a qualitative case study and evaluation.

BACKGROUND: Priority setting is one of the most difficult issues facing hospitals because of funding restrictions and changing patient need. A deadly communicable disease outbreak, such as the Severe Acute Respiratory Syndrome (SARS) in Toronto in 2003, amplifies the difficulties of hospital priority setting. The purpose of this study is to describe and evaluate priority setting in a hospital in response to SARS using the ethical framework 'accountability for reasonableness'. METHODS: This study was conducted at a large tertiary hospital in Toronto, Canada. There were two data sources: 1) over 200 key documents (e.g. emails, bulletins), and 2) 35 interviews with key informants. Analysis used a modified thematic technique in three phases: open coding, axial coding, and evaluation. RESULTS: Participants described the types of priority setting decisions, the decision making process and the reasoning used. Although the hospital leadership made an effort to meet the conditions of 'accountability for reasonableness', they acknowledged that the decision making was not ideal. We described good practices and opportunities for improvement. CONCLUSIONS: 'Accountability for reasonableness' is a framework that can be used to guide fair priority setting in health care organizations, such as hospitals. In the midst of a crisis such as SARS where guidance is incomplete, consequences uncertain, and information constantly changing, where hour-by-hour decisions involve life and death, fairness is more important rather than less.

Attitude of Health Personnel↗
PubMed2004

Phase I study of the proteasome inhibitor bortezomib in pediatric patients with refractory solid tumors: a Children's Oncology Group study (ADVL0015).

PURPOSE: To determine the maximum-tolerated dose, dose-limiting toxicity (DLT), and pharmacodynamics of the proteasome inhibitor bortezomib (formerly PS-341) in children with recurrent or refractory solid tumors. PATIENTS AND METHODS: An intravenous bolus of bortezomib was administered twice weekly for 2 consecutive weeks at either 1.2 or 1.6 mg/m2/dose followed by a 1-week rest. The pharmacodynamics of bortezomib were evaluated by measurement of whole blood 20S proteasome activity. RESULTS: Fifteen patients, 11 assessable, were enrolled between November 2001 and February 2003. Dose-limiting thrombocytopenia, which prevented administration of a complete course (four doses in 2 weeks) of therapy, occurred in two of five assessable children enrolled at the 1.6 mg/m2 dose level. There were no other DLTs. Inhibition of 20S proteasome activity seemed to be dose dependent. The average inhibition 1 hour after drug administration on day 1 was 67.2% +/- 7.6% at the 1.2 mg/m2/dose and 76.5% +/- 3.3% at the 1.6 mg/m2/dose. There were no objective antitumor responses. CONCLUSION: Bortezomib is well tolerated in children with recurrent or refractory solid tumors. The recommended phase II dose of bortezomib for children with solid tumors is 1.2 mg/m2/dose, administered as an intravenous bolus twice weekly for 2 weeks followed by a 1-week break.

Biological Availability↗
PubMed2004

Pharmacokinetics of O(6)-benzylguanine in pediatric patients with central nervous system tumors: a pediatric oncology group study.

PURPOSE: To report the results of the first pharmacokinetic study in pediatric patients of O(6)-benzylguanine (O(6)BG), which irreversibly inactivates the DNA repair protein alkylguanine-alkyltransferase, thus enhancing the cytotoxicity of nitrosoureas. EXPERIMENTAL DESIGN: As part of a Pediatric Oncology Group Phase I study, 120 mg/m(2) of O(6)BG was administered i.v. over 1 h, before 1,3-bis(2-chloroethyl)-1-nitrosourea administration in children with recurrent or refractory brain tumors. Serial blood samples for plasma pharmacokinetic studies were obtained. Concentrations of O(6)BG and its active metabolite O(6)-benzyl-8-oxoguanine (8-oxo-O(6)BG) were measured by high-performance liquid chromatography. A pharmacokinetic model and additional first-order elimination rate constants for each compound were developed. RESULTS: O(6)BG concentration versus time data were evaluated for 25 patients. The peak concentration of O(6)BG (mean +/- SD) was 11 +/- 4 microm, and the peak concentration of its active metabolite, 8-oxo-O(6)BG, was 35 +/- 10 microm. O(6)BG was rapidly eliminated with a half-life of 85 +/- 140 min, area under the curve of 795 +/- 320 microm. min and clearance of 760 +/- 400 ml/min/m(2). The area under the curve of 8-oxo-O(6)BG when extrapolated to infinity was 22,700 +/- 11,800 microm. min. The clearance and terminal half-life of 8-oxo-O(6)BG were 30 +/- 15 ml/min/m(2) and 360 +/- 220 min, respectively. CONCLUSIONS: There is rapid elimination of O(6)BG after i.v. administration over 1 h. In contrast, the terminal half-life for the active metabolite, 8-oxo-O(6)BG, is 4-fold longer. The pharmacokinetic parameters for O(6)BG and 8-oxo-O(6)BG are similar to those reported previously in adults.

Adolescent↗
PubMed2004

Imatinib mesylate (STI571) for treatment of children with Philadelphia chromosome-positive leukemia: results from a Children's Oncology Group phase 1 study.

The purpose of this study was to determine dose-limiting toxicities and pharmacokinetics of imatinib in children with refractory or recurrent Philadelphia chromosome-positive (Ph(+)) leukemias. Oral imatinib was administered daily at dose levels ranging from 260 to 570 mg/m(2). Plasma pharmacokinetic studies were performed on days 1 and 8 of course 1. There were 31 children who received 479 courses of imatinib. The most common toxicities encountered, which occurred in less than 5% of courses, were grade 1 or 2 nausea, vomiting, fatigue, diarrhea, and reversible increases in serum transaminases. One patient at the 440-mg/m(2) dose level had dose-limiting weight gain. There were no other first-course dose-limiting toxicities. A maximum tolerated dosage was not defined. Among 12 chronic myeloid leukemia (CML) patients evaluable for cytogenetic response, 10 had a complete response and 1 had a partial response. Among 10 acute lymphoblastic leukemia (ALL) patients evaluable for morphologic response, 7 achieved an M1 and 1 achieved an M2 bone marrow. We observed marked interpatient variability in the pharmacokinetic parameters. In conclusion, we found that daily oral imatinib is well tolerated in children at doses ranging from 260 to 570 mg/m(2). Doses of 260 and 340 mg/m(2) provide systemic exposures similar to those of adults who are treated with daily doses of 400 and 600 mg, respectively.

Adolescent↗
PubMed2004

Phase I trial of tirapazamine and cyclophosphamide in children with refractory solid tumors: a pediatric oncology group study.

PURPOSE: To determine the dose limiting toxicity (DLT), maximum-tolerated dose (MTD), and pharmacokinetic profile of tirapazamine (Sanofi Synthelabo Research, Malvern, PA) combined with cyclophosphamide in children with recurrent solid tumors. PATIENTS AND METHODS: Patients received a 2-hour infusion of tirapazamine, followed by 1,500 mg/m(2) cyclophosphamide, and mesna once every 3 weeks. Dose escalation of tirapazamine began at 250 mg/m(2) and was increased by 30% in subsequent cohorts. If DLT was hematologic, less-heavily pretreated patients were to be enrolled until their DLTs were encountered, and MTDs defined. Pharmacokinetic profiles were also characterized. RESULTS: Twenty-three patients were enrolled onto the study. Pharmacokinetic data were calculated for 22 patients. Prolonged neutropenia was the DLT at 420 mg/m(2) in heavily pretreated patients. Grade 3, reversible ototoxicity was the DLT in less-heavily pretreated patients at 420 mg/m(2). Two (one with neuroblastoma and one with rhabdomyosarcoma) had partial responses. One child with neuroblastoma had prolonged stable disease (10 cycles) at a dose of 250 mg/m(2). This patient had disease detectable in the bone marrow only and all evidence of bone marrow involvement resolved for 17 cycles of therapy. Four other patients had stable disease. An apparent dose-proportional increase in tirapazamine maximal concentration and area under the curve(last) was observed. Tirapazamine clearance, volume of distribution at steady-state, and terminal half-life did not appear to be dose-dependent. CONCLUSION: The recommended dose of tirapazamine given with 1,500 mg/m(2) of cyclophosphamide once every 3 weeks is 325 mg/m(2). Neutropenia and ototoxicity were dose-limiting. Based on early evidence of antitumor activity, additional studies appear warranted.

Adolescent↗
PubMed2004

Doctors' duty to disclose error: a deontological or Kantian ethical analysis.

Medical (surgical) error is being talked about more openly and besides being the subject of retrospective reviews, is now the subject of prospective research. Disclosure of error has been a difficult issue because of fear of embarrassment for doctors in the eyes of their peers, and fear of punitive action by patients, consisting of medicolegal action and/or complaints to doctors' governing bodies. This paper examines physicians' and surgeons' duty to disclose error, from an ethical standpoint; specifically by applying the moral philosophical theory espoused by Immanuel Kant (ie. deontology). The purpose of this discourse is to apply moral philosophical analysis to a delicate but important issue which will be a matter all physicians and surgeons will have to confront, probably numerous times, in their professional careers.

Bioethical Issues↗
PubMed2004

A qualitative study of attitudes toward error in patients facing brain tumour surgery.

BACKGROUND: Medical error is an extremely important component of patient safety and requires intense study. The present investigation undertook to examine patients' perceptions and attitudes regarding medical error. METHODS: Qualitative case study methodology was used. We conducted 30 face-to-face interviews with patients within one week of undergoing a neurosurgical operation for a brain tumour. Interviews were audiotaped and transcribed and the data subjected to thematic analysis. RESULTS: Three overarching themes emerged from the data: 1) trust in the patient's surgeon was of paramount importance; 2) patients' views toward medical error varied between fear and vulnerability to no concern; and 3) discussion of error was felt to be beneficial as it could help the medical profession decrease future errors and could help dispel the patient's fear and anxiety about the upcoming surgery. CONCLUSIONS: Patients' trust in their physician/surgeon is of paramount importance in allaying their fears about the possible occurrence and impact of medical error during their treatment. The level of concern about error varies among patients, but most felt that discussion of error was a good thing.

Adolescent↗
PubMed2004

Enhancement of antineoplastic action of 5-aza-2'-deoxycytidine by phenylbutyrate on L1210 leukemic cells.

Epigenetic changes, such as aberrant DNA methylation that silences tumor suppressor genes (TSGs), can play an important role in the development of leukemia. The DNA methylation inhibitor, 5-aza-2'-deoxycytidine (5-AZA-CdR), can reactivate these silent TSGs and is an interesting agent to investigate for therapy of leukemia. It has been reported that the effectiveness of 5-AZA-CdR to reactivate TSG can be enhanced by inhibitors of histone deacetylase (HDIs). HDIs can convert a compact chromatin structure to an open configuration that facilitates gene expression. An interesting HDI is phenylbutyrate (PB), which has shown some clinical activity for the therapy of leukemia. In this report we have investigated the antineoplastic activity of 5-AZA-CdR and PB alone and in combination on murine L1210 lymphoid leukemic cells. The in vitro treatment of 5-AZA-CdR and PB in combination produced a greater inhibition of growth, DNA synthesis, and also a greater reduction on colony formation on both L1210 and human HL-60 leukemic cells as compared to either drug alone. The combination also produced a synergistic activation of the TSG, p15CDN2B, in the L1210 cells. In mice with L1210 leukemia the combination showed enhanced antineoplastic activity. We also observed an enhancement of the antineoplastic activity of this combination in mice with L1210 leukemia. These data provide a rationale to investigate 5-AZA-CdR and PB in patients with advanced leukemia.

Animals↗
PubMed2004

Neo-speciesism.

Explore the source record for details and available documents.

Animal Rights↗
PubMed2004

Surgical innovation or surgical evolution: an ethical and practical guide to handling novel neurosurgical procedures.

OBJECT: Surgical innovation is an important driver of improvements in technique and technology, which ultimately translates into improvements in patients' outcomes. Nevertheless, patients may face new risks of morbidity and mortality when surgical innovation is used, and well-intentioned surgical "experimentation" on patients must be regulated and monitored. In this paper the authors examine the challenges of defining surgical innovation and briefly review the literature on this challenging subject. METHODS: Using examples from the field of neurosurgery and in part from the personal experience of the senior author, the authors develop a model of levels of experimental acuity of surgical procedures and offer recommendations on how these procedures would best be regulated. CONCLUSIONS: The authors propose guidelines for determining the need for regulation of innovation. The potential role of institutional review boards in this process is highlighted.

Diffusion of Innovation↗
PubMed2004

Surgical outreach clinics in Canada: one neurosurgeon's experience.

In this short paper, I present my 3-year experience, from January 2000 to September 2002, with a neurosurgery consultation outreach clinic in Huntsville, Ont. I describe the logistics, advantages, disadvantages and implications for surgeons of outreach clinics and their patients. The clinic was highly successful for the area physicians and the patients, but was discontinued in September 2002 owing to restrictions on my time available for the clinic. New surgical outreach clinics should be carefully planned. The specialist surgeon must have adequate flexibility and time for this activity and the success of the clinic must be assessed regularly.

Ambulatory Care↗
PubMed2004

Antineoplastic action of 5-aza-2'-deoxycytidine (Dacogen) and depsipeptide on Raji lymphoma cells.

Epigenetic alterations, such as aberrant DNA methylation and histone deacetylation, can silence genes that suppress leukemogenesis. The objective of our study was to investigate the in vitro antineoplastic and gene re-activation activity of 5-aza-2'-deoxycytidine (5AZA), a potent inhibitor of DNA methylation, and depsipeptide (depsi), an inhibitor of histone deacetylase, on Raji lymphoma cells. The combination of 5AZA with depsi produced a significantly greater inhibition of growth and colony formation than either agent alone. Using RT-PCR, we observed that combination also produced a synergistic activation of E-cadherin, a gene that is silenced by aberrant DNA methylation in Raji cells. This latter interaction indicates that there is cross-talk between DNA methylation and histone modifications in chromatin for E-cadherin in this cell line. 5AZA and depsi may be an interesting drug combination to investigate in patients with lymphoma.

Antimetabolites, Antineoplastic↗
PubMed2004

The nursing role in patient education regarding outpatient neurosurgical procedures.

The shift towards patient-centred care is the priority in health care today. Providing quality care that is highly efficient and patient-friendly while also being cost-effective is a difficult, but not impossible task. Since 1996, awake, image-guided day surgery for resection of brain tumors has been performed at Toronto Western Hospital in an attempt to combine the concept of patient-centred care with responsible resource allocation. Nurses can play a vital role in facilitating a shift in outpatient neurosurgery towards a more patient-care focused environment. By providing information and education to patients and families, nurses have enormous potential to improve satisfaction and outcomes for patients undergoing these procedures. Thoroughly preparing patients for their surgery and helping them manage their care post-operatively are the keys to decreased complications and re-admission. This would undoubtedly improve cost-effectiveness for the system while simultaneously improving the patients' quality of life.

Ambulatory Surgical Procedures↗