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Biomedical subjects

M S Schwartz

Publications and source records attributed to M S Schwartz.

At least 19 recordsLinked to original sources
PubMed2003

Comparative analyses of multi-species sequences from targeted genomic regions.

The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding and conserved non-coding regions, including regulatory elements, and provide insight into the forces that have rendered modern-day genomes. As a complement to whole-genome sequencing efforts, we are sequencing and comparing targeted genomic regions in multiple, evolutionarily diverse vertebrates. Here we report the generation and analysis of over 12 megabases (Mb) of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, including the gene mutated in cystic fibrosis. These sequences show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region. In particular, we identify substantial numbers of conserved non-coding segments beyond those previously identified experimentally, most of which are not detectable by pair-wise sequence comparisons alone. Analysis of transposable element insertions highlights the variation in genome dynamics among these species and confirms the placement of rodents as a sister group to the primates.

Animals↗
PubMed2002

[Evaluation of dreams by the neuropsychological approach. Utility in the characterization of cerebral correlates in oneiric activity by functional neuroimaging].

Recent neuroimaging studies show that human REM sleep is characterized by a specific pattern of regional brain activity. While being usually interpreted in relation to physiological and cellular mechanisms, the regionally-specific distribution of brain activity during REM sleep may also be linked to specific dream features. Remarkably, several bizarre features of dreams present similarities with wellknown neuropsychological syndromes after brain damage, such as delusional misidentifications for faces and places. We propose that neuropsychological analysis of dream content might offer new ways of interpreting neuroimaging maps, as well as specific predictions for future neuroimaging studies.

Brain Injuries↗
PubMed2001

Transcrusal approach to the petroclival region with hearing preservation. Technical note and illustrative cases.

As a term, the "petrosal approach" to the petroclival region has a variety of meanings. The authors define a common nomenclature based on historical contributions and add new terminology to describe a technique of hearing preservation that allows for greater exposure of the petroclival region. The degree of temporal bone dissection defines five stages of operation. The authors used the second or "transcrusal" stage, in which the posterior and superior semicircular canals are sacrificed while preserving hearing, in six consecutive cases. Use of a common terminology ensures better understanding among surgeons. In the authors' hands, hearing has been successfully preserved in six patients after partial labyrinthectomy.

Adult↗
PubMed2000

Classification and quantification of the petrosal approach to the petroclival region.

OBJECT: The petrosal approach to the petroclival region has been used by a variety of authors in various ways and the terminology has become quite confusing. A systematic assessment of the benefits and limitations of each approach is also lacking. The authors classify their approach to the middle and upper clivus, review the applications for each, and test their hypotheses on a cadaver model by using frameless stereotactic guidance. METHODS: The petrosal approach to the upper and middle clivus is divided into four increasingly morbidity-producing steps: retrolabyrinthine, transcrusal (partial labyrinthectomy), transotic, and transcochlear approaches. Four latex-injected cadaveric heads (eight sides) underwent dissection in which frameless stereotactic guidance was used. An area of exposure 10 cm superficial to a central target (working area) was calculated. The area and length of clival exposure with each subsequent dissection was also calculated. The retrolabyrinthine approach spares hearing and facial function but provides for only a small window of upper clival exposure. The view afforded by what we have called the transcrusal approach provides for up to four times this exposure. The transotic and transcochlear procedures, although producing more morbidity, add little in terms of a larger clival window. However, with each step, the surgical freedom for manipulation of instruments increases. CONCLUSIONS: The petrosal approach to the upper and middle clivus is useful but should be used judiciously, because levels of morbidity can be high. The retrolabyrinthine approach has limited utility. For tumors without bone invasion, the transcrusal approach provides a much more versatile exposure with an excellent chance of hearing and facial nerve preservation. The transotic approach provides for greater versatility in treating lesions but clival exposure is not greatly enhanced. Transcochlear exposure adds little in terms of intradural exposure and should be reserved for cases in which access to the petrous carotid artery is necessary.

Cranial Fossa, Posterior↗
PubMed1999

What is applied psychophysiology? Toward a definition.

This paper presents a proposed working definition of "applied psychophysiology." The paper reviews the background for the term, reasons for formalizing a definition, and boundaries. The working definition, explanation of key terms, and inclusion and exclusion criteria are then presented. Selected questions are then addressed such as whether physiology always has to be measured, and the boundaries such as distinguishing applied psychophysiology from psychotherapy.

Humans↗
PubMed1999

Some hypothalamic hamartomas contain transforming growth factor alpha, a puberty-inducing growth factor, but not luteinizing hormone-releasing hormone neurons.

Activation of LH-releasing hormone (LHRH) secretion, essential for the initiation of puberty, is brought about by the interaction of neurotransmitters and astroglia-derived substances. One of these substances, transforming growth factor alpha (TGFalpha), has been implicated as a facilitatory component of the glia-to-neuron signaling process controlling the onset of female puberty in rodents and nonhuman primates. Hypothalamic hamartomas (HH) are tumors frequently associated with precocious puberty in humans. The detection of LHRH-containing neurons in some hamartomas has led to the concept that hamartomas advance puberty because they contain an ectopic LHRH pulse generator. Examination of two HH associated with female sexual precocity revealed that neither tumor had LHRH neurons, but both contained astroglial cells expressing TGFalpha and its receptor. Thus, some HH may induce precocious puberty, not by secreting LHRH, but via the production of trophic factors--such as TGFalpha--able to activate the normal LHRH neuronal network in the patient's hypothalamus.

Astrocytes↗
PubMed1999

Use of the radial forearm microvascular free-flap graft for cranial base reconstruction.

OBJECT: Reconstruction of the cranial base after resection of complex lesions requires creation of both a vascularized barrier to cerebrospinal fluid (CSF) leakage and tailored filling of operative defects. The authors describe the use of radial forearm microvascular free-flap grafts to reconstruct skull base lesions, to fill small tissue defects, and to provide an excellent barrier against CSF leakage. METHODS: Ten patients underwent 11 skull base procedures including placement of microvascular free-flap grafts harvested from the forearm and featuring the radial artery and its accompanying venae comitantes. Operations included six craniofacial, three lateral skull base, and two transoral procedures for various diseases. Excellent results were obtained, with no persistent CSF leaks, no flap failures, and no operative infections. One temporary CSF leak was easily repaired with flap repositioning, and at one flap donor site minor wound breakdown was observed. One patient underwent a second procedure for tumor recurrence and CSF leakage at a site distant from the original operation. CONCLUSIONS: Microvascular free tissue transfer reconstruction of skull base defects by using the radial forearm flap provides a safe, reliable, low-morbidity method for reconstructing the skull base and is ideally suited to "low-volume" defects.

Adult↗
PubMed1999

Quantification of increased exposure resulting from orbital rim and orbitozygomatic osteotomy via the frontotemporal transsylvian approach.

OBJECT: Use of orbital rim and orbitozygomatic osteotomy has been extensively reported to increase exposure in neurosurgical procedures. However, there have been few attempts to quantify the extent of additional exposure gained by these maneuvers. Using a novel laboratory technique, the authors have attempted to measure the increase in the "area of exposure" that is gained by removal of the orbital rim and zygomatic arch via the frontotemporal transsylvian approach. METHODS: The authors dissected five cadavers bilaterally. The area of exposure provided by the frontotemporal transsylvian approach was determined by using a frameless stereotactic device. With the tip of a microdissector placed on targets deep within the exposure, the position of the end of the microdissector handle was measured in three-dimensional space as the microdissector was rotated around the periphery of the operative field. This maneuver was performed via the frontotemporal approach alone as well as with orbital rim and orbitozygomatic osteotomy approaches. After data manipulation, the areas of exposure corresponding to the polygons used to define these handle positions were calculated and directly compared. On average, the area of exposure provided by the frontotemporal transsylvian approach was increased 26 to 39% (p<0.05) by adding orbital rim osteotomy and an additional 13 to 22% (not significant) with removal of the zygomatic arch. CONCLUSIONS: Significant and consistent increases in surgical exposure were obtained by using orbital osteotomy, whereas zygomatic arch removal produced less consistent gains. Both maneuvers may be expected to improve surgical access. However, because larger and more consistent gains were afforded by orbital rim removal, the threshold for removal of this portion of the orbitozygomatic complex should be lower.

Brain Mapping↗
PubMed1998

Clonogenic inactivation of colon cancer-derived cells treated with 5-fluorouracil and indomethacin in hybrid spheroids.

The clonogenic hybrid spheroid assay has been used to determine the toxicity of 5-fluorouracil (5-FU), alone or in combination with indomethacin, in LoVo cells (a human colon adenocarcinoma line). The principal finding was that 5-FU toxicity, determined as loss of colony-forming ability, increased as a function of dose (concentration x duration of exposure), and that indomethacin causes a generalized alleviation of 5-FU toxicity, but only if given concurrently with 5-FU. The implications of these findings in the control of cancer cells by 5-FU are discussed.

Adenocarcinoma↗
PubMed1998

Dual-isotope single-photon emission computerized tomography scanning in patients with glioblastoma multiforme: association with patient survival and histopathological characteristics of tumor after high-dose radiotherapy.

OBJECT: The study was conducted to determine the association between dual-isotope single-photon emission computerized tomography (SPECT) scanning and histopathological findings of tumor recurrence and survival in patients treated with high-dose radiotherapy for glioblastoma multiforme. METHODS: Studies in which SPECT with 201Tl and 99mTc-hexamethypropyleneamine oxime (HMPAO) were used were performed 1 day before reoperation in 47 patients with glioblastoma multiforme who had previously been treated by surgery and high-dose radiotherapy. Maximum uptake of 201Tl in the lesion was expressed as a ratio to that in the contralateral scalp, and uptake of 99mTc-HMPAO was expressed as a ratio to that in the cerebellar cortex. Patients were stratified into groups based on the maximum radioisotope uptake values in their tumor beds. The significance of differences in patient gender, histological characteristics of tissue at reoperation, and SPECT uptake group with respect to 1-year survival was elucidated by using the chi-square statistic. Comparisons of patient ages and time to tumor recurrence as functions of 1-year survival were made using the t-test. Survival data at 1 year were presented according to the Kaplan-Meier method, and the significance of potential differences was evaluated using the log-rank method. The effects of different variables (tumor type, time to recurrence, and SPECT grouping) on long-term survival were evaluated using Cox proportional models that controlled for age and gender. All patients in Group I (201Tl ratio < 2 and 99mTc-HMPAO ratio < 0.5) showed radiation changes in their biopsy specimens: they had an 83.3% 1-year survival rate. Group II patients (201Tl ratio < 2 and 99mTc-HMPAO ratio of > or = 0.5 or 201Tl ratio between 2 and 3.5 regardless of 99mTc-HMPAO ratio) had predominantly infiltrating tumor (66.6%); they had a 29.2% 1-year survival rate. Almost all of the patients in Group III (201Tl ratio > 3.5 and 99mTc-HMPAO ratio > or = 0.5) had solid tumor (88.2%) and they had a 6.7% 1-year survival rate. Histological data were associated with 1-year survival (p < 0.01): however, SPECT grouping was more closely associated with 1-year survival (p < 0.001) and was the only variable significantly associated with long-term survival (p < 0.005). CONCLUSIONS: Dual-isotope SPECT data correlate with histopathological findings made at reoperation and with survival in patients with malignant gliomas after surgical and high-dose radiation therapy.

Adolescent↗
PubMed1997

The use of clinical practice guidelines (CPGs) to evaluate practice and control costs in ventriculoperitoneal shunt management.

BACKGROUND: As a step toward maximizing the quality and cost-effectiveness of neurosurgical care, we designed clinical practice guidelines (CPGs) for the management of VP shunt malfunctions and infections at a tertiary care pediatric teaching institution. The detailed CPGs determine the use of radiographic studies, laboratory tests, and invasive procedures in the management of this problem. One purpose of the CPGs is to provide clear clinical guidelines for the medical trainee, thereby reducing variability in care and unnecessary utilization of resources. METHODS: The CPGs were developed in stages over a 2-year period. The practice patterns in our institution for the management of shunt malfunctions and infections were articulated. They were compared with those published in the neurosurgical literature, and areas of clinical decision-making variability were identified. Preliminary guidelines were formulated, and data regarding patient care were prospectively collected. Based on this data, final CPGs were formulated and implemented. Total and itemized hospital charges for patients managed according to the CPGs were compared with those for patients in the 3 years before CPG implementation. RESULTS: CPG-managed patients had generally lower total and itemized charges as compared with control patients. Decreased charges per hospital day and charges for shunt films in the CPG group were statistically significant. CONCLUSIONS: The process by which the CPGs were developed and implemented, as well as the CPGs themselves, are described. We also present the clinical, demographic, and financial data that were prospectively collected for all patients managed within the CPGs over an initial 1-year period and compare it with data obtained for control groups of shunt malfunction patients admitted during the 3 years before implementation of the CPGs. We find a trend toward reduction of charges after implementation of the CPG.

Boston↗
PubMed1997

Post-transplant hyperlipidaemia: low-dose lovastatin lowers atherogenic lipids without plasma accumulation of lovastatin.

OBJECTIVES: The purpose of the present study was twofold. First, to determine the frequency of hyperlipidaemia after heart transplantation (Tx) in relation to values obtained before Tx. Secondly, to examine the effect of low-dose lovastatin on possible antiatherogenic mechanisms and test the hypothesis that the side-effects are dose-dependent. SUBJECTS AND DESIGN: Retrospective study of the frequency of hyperlipidaemia disturbances in heart transplant patients. In addition, in a prospective study, the safety and efficacy of incremental low doses of lovastatin up to 20 mg day-1 were studied, with measurements of its plasma concentration in 24 cyclosporin A treated heart (n = 14) and kidney (n = 10) recipients with total cholesterol > 7.5 mmol L-1. RESULTS: Cholesterol increased markedly after heart transplantation from a pretransplant value of 5.3 (5.0,5.6) mmol L-1 to 6.7 (6.4,7.0) mmol L-1 after 1 year and then remained constant, but this increase was largely due to a 'normalization' since cholesterol decreased significantly during increasing heart failure before transplantation. Treatment with lovastatin decreased total cholesterol by 19% (P < 0.001), primarily by an effect on LDL cholesterol. HDL cholesterol increased by 15% (P < 0.05), whereas triglycerides remained unchanged. Lovastatin also caused a significant reduction in apolipoprotein B of 16%, and lipid peroxidation of 40%, whereas apolipoprotein A-I, fibrinogen, and glycerol were unchanged. Plasma concentration of lovastatin was significantly higher in transplant recipients compared with controls, but there was no accumulation during incremental dosing of lovastatin. The drug was well tolerated without significant symptoms or evidence of myopathy. CONCLUSIONS: Hyperlipidaemia is common after cardiac transplantation. Treatment with low dose lovastatin is well tolerated and has a favourable effect on atherogenic lipids.

Adult↗