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Biomedical subjects

Mark Bernstein

Publications and source records attributed to Mark Bernstein.

At least 55 records · Page 3Linked to original sources
PubMed2003

Biology of childhood osteogenic sarcoma and potential targets for therapeutic development: meeting summary.

Childhood osteogenic sarcoma (OS) is a rare bone cancer occurring primarily in adolescents. The North American pediatric cooperative groups have performed a series of clinical treatment trials in this disease over the past several decades, and biology studies of tumor tissue have been an important study component. A meeting was held in Bethesda, Maryland on November 29-30, 2001, sponsored by the NIH Office of Rare Diseases, the Children's Oncology Group, and the National Cancer Institute-Cancer Therapy Evaluation Program with the general objectives: (a) to review the current state of knowledge regarding OS biology; (b) to identify, prioritize, and support the development of biology studies of potential clinical relevance in OS; and (c) to discuss the available tissue resources and the appropriate methods for analysis of OS samples for the conduct of biology studies. This report summarizes the information presented and discussed by the meeting participants.

Angiogenesis Inhibitors↗
PubMed2003

Patient safety in surgery: error detection and prevention.

Error in medicine is becoming a well recognized phenomenon. The U.S. Institute of Medicine's publication in 1999 included estimations that medical error is the eighth leading cause of death in the United States and results in up to 100,000 deaths annually. Retrospective studies and a few prospective studies are shedding more light on this challenging problem. Strategies to reduce error and increase patient safety have not been widely developed or embraced by surgeons for a variety of reasons. We provide a review on patient safety aimed at surgeons that includes definitions, incidence of errors including those in the surgical literature, causes of error, methods of error detection, and strategies to minimize errors and maximize patient safety.

Communication↗
PubMed2003

Venous air embolism during awake craniotomy in a supine patient.

PURPOSE: To report a non-fatal case of intraoperative venous air embolism (VAE) during an awake craniotomy. VAE presented with unusual clinical features. CLINICAL FEATURES: VAE during an awake craniotomy has not been reported frequently. The patient we describe presented with persistent coughing followed by tachypnea, hypoxia and reduction in end-tidal CO(2) during dural opening while undergoing an awake craniotomy in the supine position. Cardiovascular variables were stable during the episode except for transient hypertension. Having ruled out airway obstruction and low cardiac output, we concluded that air embolism was the cause. The patient responded immediately to the standard treatment of air embolism and recovered without any complication. CONCLUSION: This case illustrates a VAE during an awake craniotomy and emphasizes the importance of early diagnosis in the management.

Brain Neoplasms↗
PubMed2003

Pain, nausea, vomiting and ocular complications delay discharge following ambulatory microdiscectomy.

OBJECTIVE: Nowadays, microsurgical discectomy is being performed as an outpatient procedure. A retrospective chart review was done to document factors that delayed discharge or led to unanticipated admission. METHODS: After Institutional Review Board approval, the hospital medical records of 106 patients who underwent microsurgical discectomy on an ambulatory basis were reviewed. All patients were operated upon by a single surgeon at the Toronto Western Hospital. Perioperative data were collected on specifically designed data sheets. All anesthetic and surgical factors that affected discharge were noted. RESULTS: Of the 106 patients reviewed, only six required unanticipated admission. Two patients were admitted due to nausea and vomiting, one due to severe pain, one due to urinary retention and two were surgical causes (dural tear). Eight patients had delayed discharge. Anesthesia causes were severe nausea, severe pain, low oxygen saturation, sore throat and dry eyes. Two patients had surgical causes. The incidence of postoperative nausea was 61% and postoperative vomiting was 9.4%. Eighty patients (75.4%) complained of pain in the postanesthesia care unit. Of these, 33.9% had visual analogue pain scale scores more than 6. CONCLUSION: Ambulatory lumbar microdiscectomy can be carried out as an ambulatory procedure with an acceptably low unanticipated admission rate (5.7%). The percentage of patients with severe nausea (16%) and pain (33.9%) is high. Adequate perioperative pain management and effective control of nausea and vomiting may further improve the patients' experience after anesthesia for ambulatory microdiscectomy.

Adult↗
PubMed2003

Preclinical evaluation of antineoplastic activity of inhibitors of DNA methylation (5-aza-2'-deoxycytidine) and histone deacetylation (trichostatin A, depsipeptide) in combination against myeloid leukemic cells.

During the development of leukemia, genes that suppress growth and induce differentiation can be silenced by aberrant DNA methylation and by changes in chromatin structure that involve histone deacetylation. It has been reported that a positive interaction between DNA methylation and histone deacetylation takes place to inhibit transcription. Based on this observation, our working hypothesis was that a combination of inhibitors of these processes should produce an enhancement of their antineoplastic activity on leukemic cells. The cytosine nucleoside analog, 5-aza-2'-deoxycytidine (5AZA), is a potent inhibitor of DNA methylation, which can activate tumor suppressor genes in leukemic cells that have been silenced by aberrant methylation. In clinical trials, 5AZA was demonstrated to be an active antileukemic agent. Histone deacetylase inhibitors (HDI) can also activate gene expression in leukemic cell lines by producing changes in chromatin configuration, and show antineoplastic activity in preclinical studies. In this report, we investigated the in vitro antineoplastic activity of 5AZA, alone and in combination with the HDI, trichostatin A (TSA) and depsipeptide (FR901228, depsi), on the human myeloid leukemic cell lines, HL-60 and KG1a. The results showed that the combination of 5AZA with TSA or depsi produced a greater inhibition of growth and DNA synthesis and a greater loss of clonogenicity than either agent alone. These results suggest that 5AZA used in combination with HDI may be an interesting chemotherapeutic regimen to investigate in patients with acute myeloid leukemia that is resistant to conventional chemotherapy.

Acetylation↗
PubMed2003

Postoperative reversal of complete (monocular) blindness in skull base meningioma: case report.

BACKGROUND: Meningiomas of the anterior cranial fossa frequently present with impaired visual function. Recognition of this entity in the differential diagnosis of painless, progressive, and asymmetric optic neuropathy is important since reversal of visual loss is possible given timely surgical excision of the tumour. METHODS: A 76-year-old man presented with no perception of light in his right eye and a reduced visual acuity of 20/60 in his left eye with a markedly constricted visual field. His visual deterioration had progressed over the previous three months and was not associated with headache. Ophthalmoscopy showed normal optic discs. MRI scanning showed a large frontal basal meningioma, which was subsequently resected. RESULTS: The patient noticed an immediate improvement in his vision in his right eye. Visual acuity in his right eye improved to 20/50 at six weeks postoperatively and to 20/25 at five months, with corresponding improvement of the visual field. CONCLUSION: Complete monocular blindness due to tumour compressing or distorting the anterior visual pathways does not preclude recovery following timely decompressive surgery, especially when the appearance of the optic disc is normal.

Aged↗
PubMed2003

Phase I trial of rebeccamycin analog (NSC #655649) in children with refractory solid tumors: a pediatric oncology group study.

PURPOSE: To conduct a phase 1 trial of rebeccamycin analog (NSC #655649) in children with solid tumors to establish the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD); to establish the pharmacokinetic profile in children, and to document any evidence of antitumor activity. METHODS: A 1-hour infusion of NSC #655649 was administered every 21 days to 17 patients younger than 21 years who had malignant tumors refractory to conventional therapy. Doses ranged from 450 mg/m2 to 760 mg/m2. Pharmacokinetics were done in at least three patients per dose level. The first course was used to determine DLT and MTD. RESULTS: Sixteen patients on three dose levels were assessable for toxicities. At 760 mg/m2, four patients had dose-limiting neutropenia and thrombocytopenia. Pharmacokinetics were assessable in 13 patients. Plasma concentrations declined triexponentially and concentrations above the range of in vitro antitumor activity were maintained for 3 days. Analysis of urine extracts revealed the presence of an N-de-ethylated metabolite and probable involvement of cytochrome P450 isoenzyme(s) in the metabolism of NSC #655649. Pharmacodynamic studies showed a relationship between the area under the curve and percentage change in absolute neutrophil count in the E(max) model (r2 = 0.56, P = 0.001). CONCLUSIONS: The recommended phase 2 dose of NSC #655649 administered as a 1-hour infusion every 21 days to children with solid tumors is 585 mg/m2. Both neutropenia and thrombocytopenia were found to be dose-limiting toxicities.

Adolescent↗
PubMed2003

SARS and ethics.

SARS is a devastating disease that caused widespread morbidity and mortality, as well as tremendous fear and uncertainty across the global village. There are numerous challenging medical aspects of this disease. Methods required to control it also raised significant ethical challenges for decision-markers both in real time, and for the future. A group at the Joint Centre for Bioethics (JCB) at the University of Toronto formally explored the ethical dimensions of this outbreak. The author briefly reviews the analysis by the JCB group and further examines how bioethical principles and theories relate to the numerous ethical issues raised by SARS and the methods used in its containment.

Bioethics↗
PubMed2003

Capillary hemangioma of the cavernous sinus. Report of two cases.

Capillary hemangiomas are rare benign vascular tumors that tend to occur in children. Whereas the majority of hemangiomas may regress spontaneously, those associated with functional sequelae or severe symptoms may require treatment. Two patients with capillary hemangiomas of the cavernous sinus that caused neurological symptoms were treated with fractionated stereotactic radiation therapy. Both hemangiomas had shown a progressive increase in size during observation before radiation therapy; both tumors regressed after radiotherapy. Up to the time of the last follow-up evaluation both patients experienced symptomatic relief after radiation. One patient's tumor remains in complete remission and the second tumor continues to demonstrate minor residual contrast enhancement without progression. The authors conclude that fractionated stereotactic radiation therapy is a useful treatment modality in the management of symptomatic capillary hemangiomas when these tumors arise in regions of the brain or skull base in which a complete resection cannot be accomplished.

Adolescent↗
PubMed2003

Framework for bioethical assessment of an article on therapy.

OBJECT: Frameworks for scientific assessment of articles on therapy published in the medical literature have become available and will likely enhance the quality of medical research that is published in peer-reviewed journals. Comprehensive frameworks do not exist for the assessment of bioethical issues pertaining to research on human volunteers. METHODS: The authors have developed a framework consisting of ethical dimensions or questions that they suggest should be applied to assess the bioethical integrity of articles on therapy. Thirteen questions were developed and discussed in the context of current bioethical principles, and examples were applied where possible. CONCLUSIONS: The simple framework the authors have developed offers a method to assess key bioethical issues surrounding an article on therapy and probably defines the minimum standard to which such articles should be held. Many ethical questions cannot yet be answered based on available information or bioethical theories. The authors are not suggesting that their framework is comprehensive; refinements and individualization of it to fit specific studies are probably required by each clinician-researcher who designs a therapy trial and reports its results.

Bioethical Issues↗
PubMed2003

Perioperative complications and neurological outcomes of first and second craniotomies among patients enrolled in the Glioma Outcome Project.

OBJECT: In many new clinical trials of patients with malignant gliomas surgical intervention is incorporated as an integral part of tumor-directed interstitial therapies such as gene therapy, biodegradable wafer placement, and immunotherapy. Assessment of toxicity is a major component of evaluating these novel therapeutic interventions, but this must be done in light of known complication rates of craniotomy for tumor resection. Factors predicting neurological outcome would also be helpful for patient selection for surgically based clinical trials. METHODS: The Glioma Outcome Project is a prospectively compiled database containing information on 788 patients with malignant gliomas that captured clinical practice patterns and patient outcomes. Patients in this series who underwent their first or second craniotomy were analyzed separately for presenting symptoms, tumor and patient characteristics, and perioperative complications. Preoperative and intraoperative factors possibly related to neurological outcome were evaluated. There were 408 patients who underwent first craniotomies (C1 group) and 91 patients who underwent second ones (C2 group). Both groups had similar patient and tumor characteristics except for their median age (55 years in the C1 group compared with 50 years in the C2 group; p = 0.006). Headache was more common at presentation in the C1 group, whereas papilledema and an altered level of consciousness were more common at presentation in patients undergoing second surgeries. Perioperative complications occurred in 24% of patients in the C1 group and 33% of patients in the C2 group (p = 0.1). Most patients were the same or better neurologically after surgery, but more patients in the C2 group (18%) displayed a worsened neurological status than those in the C1 group (8%; p = 0.007). The Karnofsky Performance Scale score and, in patients in the C2 group, tumor size were important neurological outcome predictors. Regional complications occurred at similar rates in both groups. Systemic infections occurred more frequently in the C2 group (4.4 compared with 0%; p < 0.0001) as did depression (20 compared with 11%; p = 0.02). The perioperative mortality rate was 1.5% for the C1 group and 2.2% for the C2 group (p = not significant). The median length of the hospital stay was 4 days in each group. CONCLUSIONS: Perioperative complications occur slightly more often following a second craniotomy for malignant glioma than after the first craniotomy. This should be considered when evaluating toxicities from intraoperative local therapies requiring craniotomy. Nevertheless, most patients are neurologically stable or improved after either their first or second craniotomy. This data set may serve as a benchmark for neurosurgeons and others in a discussion of operative risks in patients with malignant gliomas.

Central Nervous System Neoplasms↗
PubMed2003

Survival following surgery and prognostic factors for recently diagnosed malignant glioma: data from the Glioma Outcomes Project.

OBJECT: The Glioma Outcomes Project represents a contemporary analysis of the management of malignant (Grade III and Grade IV/GBM) gliomas in North America. This observational database was used to evaluate the influence of resection, as opposed to biopsy, on patient outcome as measured by the length of survival. Attempts were made to reduce the impact of selection bias by repeating the data analysis after omitting patients with major negative prognostic factors. METHODS: Outcome data from 788 patients accrued from multiple sites over a 4-year period (1997-2001) were analyzed with the primary outcome measure being length of survival. Of these, 565 patients with recent diagnoses formed the basis of the present analysis. Patients were systematically followed up until death or up to 24 months after enrollment in the study, and survival data were correlated with the histopathological grade and location of the tumor, the extent of surgery, the patient's performance status, and demographic factors. The median length of survival was 40.9 weeks for patients with recently diagnosed GBMs. The true median length of survival for patients with Grade III gliomas was not reached, although there was a 58% survival rate at 104 weeks. In multivariate analysis, resection rather than biopsy (p < 0.0001), age 60 years or younger (p < 0.0001), and a Karnofsky Performance Scale (KPS) score of 70 or greater (p = 0.0004) were associated with a prolonged survival time for patients with Grade III or IV gliomas. The prognostic value of resection compared with biopsy was maintained (p < 0.0001), even after eliminating patients considered to be "poor risk" (those with age > 60 years, KPS score < 70, or presence of multifocal tumors), who may have been overrepresented in the biopsy group. Survival "tails" at 24 months were 58% for Grade III gliomas and 11% for GBMs. CONCLUSIONS: These data provide Class II evidence to support tumor grade, patient's age, and patient's functional status as prognostic factors for survival in individuals with recently diagnosed malignant gliomas. Resection (compared with biopsy) is also a strong prognostic factor; however, no quantitative attempt was made to assess the true extent of the resection.

Adult↗