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Biomedical subjects

M H Epstein

Publications and source records attributed to M H Epstein.

At least 19 recordsLinked to original sources
PubMed2001

The relation between vertebral endplate shape and lumbar disc herniations.

STUDY DESIGN: Blinded review of selected and un-selected computed tomographic myelograms. OBJECTIVE: To determine whether shape of the vertebral body endplate margins is a risk factor for the development of symptomatic lumbar disc herniations. The law of LaPlace for a fluid-filled tube suggests that anular tension could be related to endplate shape and a propensity for disc herniation. SUMMARY OF BACKGROUND DATA: It was hypothesized that the law of Laplace could apply to the lumbar spine because of to the cylindrical shape of the lumbar disc and its high water content in nonelderly individuals. It was further hypothesized that differences in the radius of the curvature could place stresses on the anulus that would make posterior disc herniations more likely with "rounder" endplates. METHODS: Ninety-seven contrast computed tomography scans were reviewed at transitional L4-L5 and L5-S1 in patients under 60 years of age, without previous spine surgery and without spondylolisthesis. Determinations of disc herniations and measurements of endplates were performed by blinded observers. A ratio of these measurements was used to determine the relative circularity of the endplate. Height, weight, body mass index, and disc endplate size and shape were related to the presence of disc herniation. RESULTS: By multiple logistic regression, only endplate shape was strongly related to disc herniations. Endplate area was a less significant factor in men. CONCLUSIONS: The shape of the vertebral body margin at the endplate is an important factor contributing to the development of disc herniations at L4-L5 and L5-S1.

Female↗
PubMed2001

Gamma knife surgery for treatment of central neurocytomas. Report of four cases.

The authors investigated the use of gamma knife surgery (GKS) in the treatment of central neurocytoma, a usually benign primary brain tumor of the lateral and third ventricles. Four patients with subtotally resected or recurrent central neurocytomas were retrospectively studied. The prescription isodose was 9 to 13 Gy to the 30 to 50% peripheral isodose line. Pre- and postoperative magnetic resonance (MR) images were compared to determine the volume reduction following GKS. Follow-up review included annual MR imaging and clinical evaluation by a neurosurgeon. Follow-up periods ranged from 12 to 99 months. Marked reduction in tumor size was seen in all four patients; the decrease in tumor volume for each was 48%, 72%, 81%, and 77%, respectively, at the last follow-up review. None of the four patients required additional treatment and none experienced a decline in neurological function during the follow-up period. No complications have been noted in any of these patients to date. Even though there have been few observations and follow-up time has been limited, because of the consistency of the response and the lack of observed side effects, GKS may be the treatment of choice for subtotally resected and recurrent central neurocytomas.

Adult↗
PubMed2000

Herniated lumbar disc material as a source of free glutamate available to affect pain signals through the dorsal root ganglion.

STUDY DESIGN: Combined prospective human cohort and prospective controlled animal model. OBJECTIVES: To determine whether free glutamate is available in herniated disc material in concentrations sufficient to diffuse to glutamate receptors and affect the activity of neurons in the dorsal root ganglion that may transmit pain information. SUMMARY OF BACKGROUND DATA: The severity of lumbar radicular pain cannot be fully explained by physical pressure on nerve roots or ganglions. In experimental models, inflammatory processes are relatively modest under conditions of disc herniation. The hypothesis for the current study was that the proteoglycan link and core proteins, which contain high fractions of acidic amino acids, may be a source of glutamate when enzymatically degraded in an environment without glutamate reuptake systems. Glutamate would be free to diffuse to the dorsal root ganglion to affect glutamate receptors. METHODS: Disc material was harvested during surgery from herniated and nonherniated portions in patients undergoing elective lumbar disc surgery and subjected to immunohistochemistry and high-performance liquid chromatography for assessment of the presence of extracellular disc matrix glutamate. Miniosmotic pumps with differing concentrations of radiolabeled glutamate based on human data were implanted in the rat epidural space for 72 hours and dorsal root ganglion (DRG) in the region were harvested. RESULTS: Densitometry of disc matrix demonstrated immunohistochemical evidence for significant extracellular glutamate (P < 0.002). High performance liquid chromatography showed significant concentrations of glutamate in disc material and significantly more in herniated than in nonherniated disc material (P < 0.05). Significant radiolabeling of the dorsal root ganglion after epidural glutamate infusion was found at concentrations two orders of magnitude below measured disc glutamate levels. Autoradiography demonstrated radiolabeling of adjacent DRG. CONCLUSIONS: Glutamate originating from degenerated disc proteoglycan may diffuse to the dorsal root ganglion and effect glutamate receptors. Consideration may be given to treating disc radiculopathy with epidural glutamate receptor antagonists.

Adult↗
PubMed1997

Inhibition of growth factor mitogenicity and growth of tumor cell xenografts by a sulfonated distamycin A derivative.

Interference with growth factor-receptor interactions may have particular relevance in efforts to intervene clinically in both autocrine and paracrine aspects of malignancy. Suramin is a synthetic anticancer agent that works, in part, by blocking the binding of growth factors to their receptors. While initial clinical trials have been encouraging, its use in clinical applications is associated with significant toxicities. Suradista is a novel sulfonated distamycin derivative that is also effective at complexing and inactivating growth factors and cytokines while remaining relatively nontoxic. The goal of this study was to compare the antineoplastic properties of suramin and Suradista. To achieve this, the effects of these compounds on growth factor induced mitogenesis in normal mouse fibroblasts and human umbilical vein endothelial cells were examined, as well as their ability to inhibit the growth of NIH/3T3 cells that had been transformed by the introduction of a fibroblast growth factor (FGF) 1 coding region (residues 1-154) fused to the signal peptide of the hst/KS3 gene (sp-hst/KS3:FGF1-154). In each case, Suradista was more effective than suramin in inhibiting mitogenesis in normal cells, as well as the growth of the transformed cells. Furthermore, Suradista was also shown to be as effective as suramin at inhibiting the growth of sp-hst/KS3:FGF1-154-transformed NIH/3T3 xenografts grown in athymic nude mice when given at only 50% the dosage used for suramin (50 mg/kg for Suradista versus 100 mg/kg for suramin). In summary, these results indicate that novel compounds acting like suramin may be developed as effective antineoplastic agents and may also prove to be of clinical benefit.

3T3 Cells↗
PubMed1996

Immunohistochemical evaluation of erbB-2 and p53 protein expression in benign and atypical human meningiomas.

Meningiomas arise from the arachnoidal cells surrounding the brain and are one of the most common tumors of the central nervous system. These tumors are known to be hormonally modulated and may occur in association with breast carcinoma. Overexpression of the erbB-2 oncogene product and mutation of the tumor suppressor p53 gene are considered causal driving forces in the pathogenesis of adenocarcinomas of the breast. To determine whether abnormal expression of these genes also plays a role in the pathogenesis of meningiomas, we analyzed the expression of the erbB-2 and p53 proteins in 17 atypical and 35 typical meningioma tissue specimens by immunohistochemistry. The staining intensity was assigned a relative value of 0 to 5+, where 5+ denoted confluent immunoreactivity, 4+ to 1+ denoted varying degrees of focal positivity, and 0 denoted no evidence of staining. Levels of p53 and erbB-2 immunohistochemical staining were then correlated with tumor histology. For p53 immunoreactivity, typical meningiomas had a median staining score of 1.0, compared to 4.0 for atypical meningiomas (P < 0.0001, Mann-Whitney U test). For erbB-2 immunoreactivity, typical meningiomas had a median staining score of 5.0 compared to 1.0 for atypical meningiomas (P < 0.0001, Mann-Whitney U test). The inverse relationship between levels of erbB-2 and p53 immunoreactivity was found to be statistically significant (P < 0.0001, ANOVA). Expression of the erbB-2 protein was not associated with gene amplification or the presence of activating mutation in the transmembrane region of the protein. These findings may improve our understanding of the molecular events that occur in the neoplastic transformation of meningothelial cells. The patterns of erB-2 and p53 immunoreactivity may prove to be useful markers with which to identify potentially more malignant meningiomas.

Base Sequence↗
PubMed1996

Needs assessment of community-based services for children and youth with emotional or behavioral disorders and their families: Part 1. A conceptual model.

Communities throughout the nation are attempting to develop comprehensive systems of community-based, interagency care for children and youth with emotional or behavioral disorders and their families. Needs assessment has been identified as a key component of these initiatives. A needs assessment provides system planners with the data needed to make informed decisions with regard to improving the current system of care. In this first of a two-article series, an overview is presented of a model needs assessment designed for implementation by an interagency coalition interested in developing a comprehensive system of community-based services for children and youth with emotional or behavioral disorders and their families. Major components of the model include foundations for needs assessment, data collection, and data utilization.

Adolescent↗
PubMed1996

Needs assessment of community-based services for children and youth with emotional or behavioral disorders and their families: Part 2. Implementation in a local system of care.

In a previous article, rationale and procedures were presented for a model needs assessment of community-based services for children and youth with emotional and behavioral disorders and their families. In this article, the authors describe initial needs assessment planning activities, examine the implementation of the proposed model, provide a general overview of the results, and review how the community that conducted the assessment used the information to identify system development priorities and action plans. Quantitative data are provided on the population demographics and parent and direct services provider surveys. Qualitative data are presented on the semistructured interviews with key stakeholders and direct service providers.

Adolescent↗
PubMed1996

Stereotactic radiosurgery for trigeminal neuralgia: a multiinstitutional study using the gamma unit.

A multiinstitutional study was conducted to evaluate the technique, dose-selection parameters, and results of gamma knife stereotactic radiosurgery in the management of trigeminal neuralgia. Fifty patients at five centers underwent radio-surgery performed with a single 4-mm isocenter targeted at the nerve root entry zone. Thirty-two patients had undergone prior surgery, and the mean number of procedures that had been performed was 2.8 (range 1-7). The target dose of the radiosurgery used in the current study varied from 60 to 90 Gy. The median follow-up period after radiosurgery was 18 months (range 11-36 months). Twenty-nine patients (58%) responded with excellent control (pain free), 18 (36%) obtained good control (50%-90% relief), and three (6%) experienced treatment failure. The median time to pain relief was 1 month (range 1 day-6.7 months). Responses remained consistent for up to 3 years postradiosurgery in all cases except three (6%) in which the patients had pain recurrence at 5, 7, and 10 months. At 2 years, 54% of patients were pain free and 88% had 50% to 100% relief. A maximum radiosurgical dose of 70 Gy or greater was associated with a significantly greater chance of complete pain relief (72% vs. 9%, p = 0.0003). Three patients (6%) developed increased facial paresthesia after radiosurgery, which resolved totally in one case and improved in another. No patient developed other deficits or deafferentation pain. The proximal trigeminal nerve and root entry zone, which is well defined on magnetic resonance imaging, is an appropriate anatomical target for radiosurgery. Radiosurgery using the gamma unit is an additional effective surgical approach for the management of medically or surgically refractory trigeminal neuralgia. A longer-term follow-up review is warranted.

Adult↗
PubMed1996

Roles of the federal and state governments in outcomes assessment.

Both federal and state governments have mandates to collect, analyze, and disseminate health care information. The federal government is the single largest payer for health care and health services research. Its agencies, the Healthcare Finance Administration (HCFA) and the Agency for Healthcare Policy Research (AHCPR) play a major role in shaping information strategies for all health care stakeholders. State governments are among those stakeholders and are fertile grounds for experimentation, change, and learning. Building effective federal-state partnerships and public-private partnerships can help foster innovation in health data collection and analysis, as well as identify new strategies for information dissemination.

Data Collection↗
PubMed1995

The role of angiotensin II in the regulation of blood flow to choroid plexuses and cerebrospinal fluid formation in the rat.

The effect of peripherally administered angiotensin II (AII) on blood flow to choroid plexuses was examined in pentobarbital-anesthetized rats. The indicator fractionation method with 123I- or 125I-N-isopropyl-p-iodoamphetamine as the marker was employed to measure blood flow. Basal blood flow to choroid plexus of the lateral cerebral ventricle (LVCP) (3.19 +/- 0.23 ml g-1 min-1) was lower than that to choroid plexuses of the third (3VCP) and fourth (4VCP) ventricles (3.90 +/- 0.38 and 3.95 +/- 0.36 ml g-1 min-1, respectively). The effect of AII on choroidal blood flow varied depending on peptide dose and anatomical location of the choroidal tissue. AII infused intravenously at rates of 30 and 50 ng kg-1 min-1 decreased blood flow to both LVCP and 4VCP by 12-20%. Both lower (10 ng kg-1 min-1) and higher (100 and 300 ng kg-1 min-1) AII doses did not alter blood flow to LVCP and 4VCP. Blood flow to the 3VCP was not affected by any dose of the peptide used. In comparison, blood flow to cerebral cortex increased by 33% during intravenous AII infusion at a rate of 300 ng kg-1 min-1. The choroidal blood flow-lowering effect of moderate AII doses was abolished by both AT1 (losartan) and AT2 (PD 123319) receptor subtype antagonists (3 mg kg-1 i.v.). To determine whether the hemodynamic changes observed in choroid plexuses with moderate AII doses influence CSF formation, the ventriculocisternal perfusion was performed in rats (under the experimental conditions described) with Blue Dextran 2000 as the indicator.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1995

N-acetylcysteine enhances hippocampal neuronal survival after transient forebrain ischemia in rats.

BACKGROUND AND PURPOSE: Free radical scavengers enhance neuronal survival in some models of transient forebrain ischemia. Recent experiments have suggested that N-acetylcysteine prevents cellular injury after a reperfusion injury. No information is available regarding the neuroprotective potential of the free radical scavenger N-acetylcysteine after transient forebrain ischemia. In this study we evaluated the potential of N-acetylcysteine to improve hippocampal neuronal survival after transient forebrain ischemia in the rat. METHODS: In series A and B, ventilated, paralyzed, normothermic rats had 10 minutes of transient forebrain ischemia induced by bilateral carotid occlusion with hypotension induced by blood withdrawal (mean arterial blood pressure, 45 mm Hg). In series A, animals were administered N-acetylcysteine (163 mg/kg) 30 minutes and 5 minutes before transient forebrain ischemia. In series B, N-acetylcysteine (326 mg/kg) was administered 15 minutes after transient forebrain ischemia. In series C, N-acetylcysteine (326 mg/kg) was administered 15 minutes after transient forebrain ischemia in animals with a mean arterial blood pressure of 30 mm Hg during transient forebrain ischemia. All series had normal control, sham, and vehicle treatment groups. In all series, the rats were allowed to recover and were killed at 7 days after ischemia. The effect of forebrain ischemia was assessed by evaluating the number of viable neurons at bregma sections -3.3, -3.8, and -4.3 of the CA1 region of the hippocampus. RESULTS: The results demonstrated no physiological difference among the various treatment groups. There were no differences in the number of viable neurons between the transient forebrain ischemia with no treatment group and the vehicle (saline)-treated transient forebrain ischemic groups. Animals pretreated with N-acetylcysteine (mean number of neurons, 84 +/- 6) had a significant increase (P < .05) in neuronal survival compared with vehicle-treated animals (mean number of neurons, 43 +/- 4). Animals posttreated with N-acetylcysteine (mean number of neurons, 89 +/- 9) had a significant increase in neuronal survival compared with vehicle-treated animals (mean number of neurons, 7 +/- 1). However, N-acetylcysteine protection was only partial at 45 mm Hg and did not improve neuronal survival (mean number of neurons, 22 +/- 3) in animals with a more severe ischemic insult (mean arterial blood pressure, 30 mm Hg during transient forebrain ischemia) compared with vehicle-treated animals (mean number of neurons, 10 +/- 1). CONCLUSIONS: N-Acetylcysteine partially improved neuronal survival when administered before or after ischemia following transient cerebral ischemia (mean arterial blood pressure, 45 mm Hg) but not with a more severe ischemic insult of 10 minutes of transient cerebral ischemia with a mean arterial blood pressure of 30 mm Hg.

Acetylcysteine↗
PubMed1994

AT1 receptor subtype mediates the inhibitory effect of central angiotensin II on cerebrospinal fluid formation in the rat.

The effect of central administration of angiotensin II (AII) on cerebrospinal fluid (CSF) formation was studied in pentobarbital-anesthetized, artificially-ventilated rats. CSF production was measured by the ventriculocisternal perfusion method with Blue Dextran 2000 as the indicator. Baseline value of CSF production was 3.35 +/- 0.08 microliters/min. Intracerebroventricular (i.c.v.) infusion of AII at rates of 0.5 and 5 pg/min significantly lowered (P < 0.01) CSF formation by 23% and 16%, respectively. In comparison, high peptide doses (50 and 500 pg/min) did not alter this parameter. The inhibitory effect of low AII doses on CSF formation was blocked by the i.c.v. AT1 receptor subtype antagonists, losartan and SK&F 108566 (2.4 and 2.7 ng/min, respectively), but not by the AT2 receptor subtype-specific agent, PD 123319 (3.8 ng/min). Peptide AII antagonists, [Sar1,Ile8]AII (5 ng/min), which binds to both AT1 and AT2 receptors, had a similar effect to those of AT1-specific blockers. It is concluded that AII, by controlling CSF formation, may influence the water and electrolyte balance in the brain.

Angiotensin II↗
PubMed1994

Pattern of mutant p53 expression in human astrocytomas suggests the existence of alternate pathways of tumorigenesis.

BACKGROUND: Clinical observations suggest that malignant astrocytomas may arise from well-differentiated, low-grade tumors that have undergone anaplastic progression or may develop de novo. Mutations that alter the function of the p53 gene product are thought to play a critical role in astrocytoma tumorigenesis. The authors studied the pattern of mutant p53 expression in astrocytomas to define its role in the formation of malignant tumors by these different pathways. METHODS: Tissues from 44 astrocytomas corresponding to Grades I-IV of the World Health Organization (WHO) classification were analyzed for the presence of mutations in exons 5, 7, and 8 of the p53 gene using single strand conformation polymorphism (SSCP) and sequence analysis of DNA amplified by the polymerase chain reaction. Immunostaining for mutant p53 proteins was performed on tissues fixed in formaldehyde solution and embedded in paraffin; the tissues were from these 44 astrocytomas and another 103 astrocytomas obtained from archival material. RESULTS: Tumors with mutant p53 genes were reliably identified by immunostaining for mutant p53 proteins. A higher percentage of astrocytomas of histologic Grades II-IV stained positively for p53 than were identified by mutational analysis. The average ages of patients with Grade III/IV astrocytomas with prominent (> 10%) p53 staining and those with sparse (< 10%) or no p53 staining were 44.5, 64.3, and 67.9 years, respectively (P < 0.0001). CONCLUSIONS: The pattern of mutant p53 expression is consistent with a role in driving the progression of low-grade astrocytomas to more malignant tumors. These results provide a genetic basis for the clinical observation that malignant astrocytomas resulting from anaplastic progression occur in a younger patient population than do malignant astrocytomas arising de novo.

Adult↗
PubMed1994

Statewide health information: a tool for improving hospital accountability.

BACKGROUND: By early 1994, 38 states had invested in data collection, analysis, and dissemination on the use, cost, effectiveness, and performance of hospitals. States use these data to control costs, encourage prudent purchasing, monitor effectiveness and outcomes of health care, guide health policy, and promote informed decision making. Experience in several states suggests that public release of hospital-specific data influences hospital performance. ISSUES: The value of state data organizations' databases to address issues of quality and accountability can be strengthened by ensuring the stability and growth of statewide health information systems, supporting research on information dissemination techniques, and promoting comparisons among hospitals. CONCLUSIONS: Information to measure provider performance must be placed in the public domain--to help ensure prudent and cost-effective health care purchasing and to give providers comparable information for improvement of care. State-level health databases are an essential component of the information infrastructure needed to support health reform.

Cost-Benefit Analysis↗
PubMed1994

Homework: a survey of policies in the United States.

Homework is a key area of concern in our nation's public schools, as well as a central element of collaboration between home and school. The purpose of the current study was to survey the policies of a national sample of school districts concerning homework. Specific foci of the survey included whether a homework policy had been instituted, if modifications were made in the policy for students with disabilities, the types of homework, the length and frequency of assignments given, and specific communication mechanisms between home and school. A total of 550 surveys were mailed, with a response rate of 48.5%. The results indicated that only 35.2% of school divisions did have a policy on homework, with 64.4% of those policies including modifications for students with disabilities. Findings in terms of frequency and amount of homework assigned, as well as home-school communication mechanisms, are highlighted. The results are discussed within the context of policy development and instructional implications.

Data Collection↗