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Biomedical subjects

H Sandler

Publications and source records attributed to H Sandler.

At least 19 recordsLinked to original sources
PubMed2000

Effect of stable fish oil on arterial thrombogenesis, platelet aggregation, and superoxide dismutase activity.

We examined the influence of dietary stable fish oil on aortic thrombosis, platelet aggregation, and superoxide dismutase (SOD) activity in a rat model. Twenty-nine Sprague-Dawley rats were fed regular chow supplemented with stable fish oil preparation (for 1 or 3 weeks), and 37 rats fed regular chow served as controls. The abdominal cavity was opened, and the abdominal aorta isolated. Whatman paper impregnated with 35% FeCl3 was wrapped around the surface of the aorta, and aortic flow was continuously recorded. In control rats, an occlusive platelet-fibrin-rich thrombus was formed in 21 +/- 3 min. Dietary fish oil in a time-dependent fashion delayed time to thrombus formation (24 +/- 2 min in rats fed fish oil for 1 week and 31 +/- 2 min in rats fed fish oil for 3 weeks), inhibited platelet aggregation (21 +/- 5% vs. 45 +/- 6%; p < 0.01) and increased SOD activity (p < 0.01). We conclude that dietary supplementation with stable fish oil delays formation of arterial thrombus, probably by reducing platelet aggregation and oxidative stress-associated arterial injury.

Animals↗
PubMed2000

NCCN Practice Guidelines for Prostate Cancer.

Systemic therapies for prostate cancer are likely to improve, and as they do, they will have enormous impact on the treatment of high-risk and locally advanced cancers. Further technical improvements in radiotherapy and alternative local modalities, such as cryoablation, are also likely, and will bring even more options for local control. It is certain these guidelines will continue to evolve.

Evidence-Based Medicine↗
PubMed1999

A phase 3 randomized study of radiotherapy plus procarbazine, CCNU, and vincristine (PCV) with or without BUdR for the treatment of anaplastic astrocytoma: a preliminary report of RTOG 9404.

PURPOSE: This study was an open label, randomized Phase 3 trial in newly diagnosed patients with anaplastic glioma comparing radiotherapy plus adjuvant procarbazine, CCNU, and vincristine (PCV) chemotherapy with or without bromodeoxyuridine (BUdR) given as a 96-hour infusion each week of radiotherapy. METHODS AND MATERIALS: Only patients 18 years or older with newly diagnosed anaplastic glioma were eligible; central pathology review was accomplished, but was not mandated prior to registration. The study had initially opened as a Northern California Oncology Group (NCOG) trial in 1991, becoming an Intergroup RTOG, SWOG, and NCCTG study in July 1994. Total accrual of 293 patients was planned as the sample size, using survival and time to tumor progression as the primary endpoints. The experiment arm (RT/BUdR plus PCV) was to be compared to the control arm (RT plus PCV) using an alpha = 0.05, one-tailed, with a power of 85% for detecting an increase in median survival from 160 to 240 weeks, assuming a 3-year follow-up after completion of enrollment. RESULTS: As of July 1996, 281 patients had been randomized; 53 (20%) were ineligible, primarily based upon central pathology review, and another 39 cases were canceled. In total, 30% of cases were excluded from analysis. The treatment arms were well balanced despite this rate of exclusion. The RTOG Data Monitoring Committee recommended suspension of enrollment in July 1996 based upon a stochastic curtailment analysis which strongly suggested that the addition of BUdR would not be associated with increased survival. In February 1997, the study was closed prior to full enrollment. At that time, the 1-year survival estimates were 82% versus 68% for RT plus PCV and RT/BUdR plus PCV respectively (one-sided, p = 0.96). The conditional power analysis indicated that even with an additional 12 months of additional accrual and follow-up the probability of detecting the prespecified difference was less than 0.01%. The differences in the two arms seem to be due to early deaths in the BUdR arm, not related to toxicity of the treatment. CONCLUSIONS: Despite encouraging Phase 2 results with BUdR, it is unlikely that a survival benefit will be seen. A final study analysis will not be done for at least 3 more years.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

[Serious effects of chloroquine overdose. Prescribe the smallest possible dosage-packages and inform about the risks].

An increasing number of acute overdoses with chloroquine has been reported in Sweden--some with fatal outcome. This substance is clearly one of the most toxic pharmaceuticals on the Swedish market. Four cases are described. Travelling to the tropics has become very popular, and chloroquine is often given as a prophylactic antimalarial. This inexpensive drug is often prescribed in 100-tablet packages, and any surplus is often stored in the home. Awareness of toxicity is low among users and doctors in this country. Preventive measures are suggested.

Adolescent↗
PubMed1998

Alzheimer changes are common in aged drivers killed in single car crashes and at intersections.

With increasing age, diseases affecting the cognitive functions are more frequent. These diseases may increase the risk for fatal car crashes. We analyzed the frequency of neuropathological alterations characteristic of Alzheimer's disease (i.e. neuritic and diffuse plaques, and neurofibrillary tangles) in two association areas of the brain, parietal and frontal cerebral cortex, from 98 fatally injured aged drivers. In the age groups of 65-75 and over 75 years of age, 50% and 72% of the drivers, respectively, had neuritic plaques in either parietal and/or frontal cortex. In 14% of all killed drivers the number of neuritic plaques reached the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) age-related histologic score C, which indicates the diagnosis of Alzheimer's disease (AD), and an additional 33% had score B, which suggests the diagnosis of AD. Neuropathological AD changes were most common in the brains of drivers killed in single vehicle crashes, followed by multivehicle crashes at intersections and least common in multivehicle crashes elsewhere, but the differences did not reach statistical significance. In a great majority (80-85%) of cases the killed aged driver was the guilty party of the crash. The results imply, that incipient AD may contribute to fatal crashes of aged drivers, and therefore the forensic autopsy of these victims should include neuropathological examination.

Accidents, Traffic↗
PubMed1998

Initial performance evaluation of an indirect-detection, active matrix flat-panel imager (AMFPI) prototype for megavoltage imaging.

PURPOSE: The development of the first prototype active matrix flat-panel imager (AMFPI) capable of radiographic and fluoroscopic megavoltage operation is reported. The signal and noise performance of individual pixels is empirically quantified. Results of an observer-dependent study of imaging performance, using a contrast-detail phantom, are detailed and radiographic patient images are shown. Finally, a theoretical investigation of the zero-frequency detective quantum efficiency (DQE) performance of such imagers, using a cascaded systems formalism, is presented. METHODS AND MATERIALS: The imager is based on a 508-microm pitch, 26 x 26 cm2 array which detects radiation indirectly via an overlying copper plate + phosphor screen converter. RESULTS: Due to its excellent optical coupling, the imager exhibits sensitivity superior to that of video-based systems. With an approximately 133 mg/cm2 Gd2O2S:Tb screen the system is x-ray quantum-noise-limited down to approximately 0.3 cGy, conservatively, and extensions of this behavior to even lower doses by means of reduced additive electronic noise is predicted. The observer-dependent study indicates performance superior to that of conventional radiotherapy film while the patient images demonstrate good image quality at 1 to 4 MU. The theoretical studies suggest that, with a 133 mg/cm2 Gd2O2S:Tb screen, the system would provide DQE performance equivalent to that of video-based systems and that almost a factor of two improvement in DQE is achievable through the incorporation of a 400 mg/cm2 screen. CONCLUSION: The reported prototype imager is the first megavoltage AMFPI having performance characteristics consistent with practical clinical operation. The superior contrast-detail sensitivity of the imager allows the capture of high-quality 6- and 15-MV images at minimal dose. Moreover, significant performance improvements, including extension of the operational range up to full portal doses, appear feasible. Such capabilities could be of considerable practical benefit in patient localization and verification.

Aged↗
PubMed1998

A leukocyte elastase inhibitor reduces thrombin-induced pulmonary oedema in the rat: mechanisms of action.

The effect of a selective leukocyte elastase inhibitor, ICI 200,355, on thrombin-induced pulmonary oedema was studied in rats. Thrombin administration produced an increase in lung weight (P < 0.05), wet weight/ dry weight ratio (P < 0.05), and relative lung water content (P < 0.05). The lung weight increase was reduced by the elastase inhibitor in doses of 2000, 200 and 20 micrograms/kg per h (P < 0.05), but not by 2 micrograms/kg per h. A dose of 20 micrograms/ kg per h seems to be optimal, since 10-fold and 100-fold increases in dose did not further improve the effect. Free elastase activity in lung tissue was higher after thrombin infusion than in controls, but was not depleted by the elastase inhibitor in vivo (P < 0.05). This elastase activity in the lung was, however, inhibited by the elastase inhibitor in vitro, indicating that the inhibitor can block extracellular, but not intracellular elastase activity. Thrombin infusion resulted in a significant decrease in plasma elastase inhibitory capacity (P < 0.05), which was depleted by the elastase inhibitor (20 micrograms/kg per h) (P < 0.05). Myeloperoxidase activity was significantly increased in lung tissue after thrombin infusion (P < 0.05). Lung myeloperoxidase activity 5 min after thrombin infusion was not affected by the elastase inhibitor, but the inhibitor induced a further increase in myeloperoxidase as seen 90 min after thrombin infusion, indicating that the effect of this inhibitor on pulmonary oedema is not due to reduction of leukocyte infiltration in the lungs, but may partly be exerted by prevention of neutrophil destruction.

Animals↗
PubMed1997

Impact of differences in ultrasound and computed tomography volumes on treatment planning of permanent prostate implants.

PURPOSE: Both ultrasound (US) and computerized tomography (CT) images have been used in the planning of prostate interstitial therapy. Ultrasound images more clearly define the apex and capsule of the prostate, while CT images define seed positions for postimplant dosimetry. Proper registration of the US volume with the CT volume is critical to the assessment of dosimetry. We therefore compared US and CT prostate volumes to determine if differences were significant. METHODS AND MATERIALS: Ten consecutive patients entered in an interstitial implant program were studied by pretreatment US. In addition, pretreatment CT scans were obtained and three physicians independently outlined the dimensions of the prostate on these images. The patients subsequently underwent placement of radioactive 125I or 103Pd. Postimplant CT images were obtained the next day and the postimplant prostate volumes were outlined by the same three physicians. Seven of 10 patients underwent late CT scans 9-14 months postimplant for comparison of preimplant and immediate postimplant CT studies. RESULTS: There were differences between US and CT volumes. Although the physician-to-physician variation was significant, the trends were consistent, with US prostate volume typically smaller (47%) than the preimplant CT volume and markedly smaller (120%) than the postimplant CT volume. Prostate volumes derived from late CT images did not consistently return to preimplant levels. CONCLUSIONS: Significant differences in volume of the prostate structure were found between US and CT images. The data suggests that: (a) Implants planned on CT tend to overestimate the size of the prostate and may lead to unnecessary implantation of the urogenital diaphragm and penile urethra. (b) Registration of initial US and postimplant CT prostate volumes required for accurate dosimetry is difficult due to the increased volume of prostate secondary to trauma. (c) Further study to determine the optimal time for the postimplant CT is necessary.

Brachytherapy↗
PubMed1996

Megavoltage imaging with a large-area, flat-panel, amorphous silicon imager.

PURPOSE: The creation of the first large-area, amorphous silicon megavoltage imager is reported. The imager is an engineering prototype built to serve as a stepping stone toward the creation of a future clinical prototype. The engineering prototype is described and various images demonstrating its properties are shown including the first reported patient image acquired with such an amorphous silicon imaging device. Specific limitations in the engineering prototype are reviewed and potential advantages of future, more optimized imagers of this type are presented. METHODS AND MATERIALS: The imager is based on a two-dimensional, pixelated array containing amorphous silicon field-effect transistors and photodiode sensors which are deposited on a thin glass substrate. The array has a 512 x 560-pixel format and a pixel pitch of 450 microns giving an imaging area of approximately 23 x 25 cm2. The array is used in conjunction with an overlying metal plate/phosphor screen converter as well as an electronic acquisition system. Images were acquired fluoroscopically using a megavoltage treatment machine. RESULTS: Array and digitized film images of a variety of anthropomorphic phantoms and of a human subject are presented and compared. The information content of the array images generally appears to be at least as great as that of the digitized film images. CONCLUSION: Despite a variety of severe limitations in the engineering prototype, including many array defects, a relatively slow and noisy acquisition system, and the lack of a means to generate images in a radiographic manner, the prototype nevertheless generated clinically useful information. The general properties of these amorphous silicon arrays, along with the quality of the images provided by the engineering prototype, strongly suggest that such arrays could eventually form the basis of a new imaging technology for radiotherapy localization and verification. The development of a clinically useful prototype offering high-quality images, ultimately with an approximately 52 x 52-cm2 detection surface, is anticipated.

Equipment Design↗
PubMed1996

Recruitment and training of minority health care managers: a case study.

This paper describes a cooperative learning model that uses six critical points of intervention at which learning can be facilitated for minority students. These six points were identified in the Health Career Opportunity Program (HCOP). The HCOP initiative model is used because it has been demonstrated that this strategy has been successful in increasing the number of minority health care professionals. The paper is presented in two parts. The first part gives an overview of the six critical points of intervention. The recommendations presented will focus on incorporating mechanisms that can facilitate the learning and achievement of minority students once they have been identified and admitted. The second part presents a case study of how these intervention strategies were implemented in the Health Services Administration Program at Meharry Medical College between the years of 1989 through 1993.

Communication↗
PubMed1995

Beneficial effects of a leukotriene receptor antagonist on thrombin-induced pulmonary edema in the rat.

The effect of a selective leukotriene receptor antagonist, the peptide ICI 198,615, on thrombin-induced pulmonary edema was studied in rats. Administration of thrombin produced a significant increase in lung weight (p < 0.05), wet weight to dry weight ratio (WW/DW; p < 0.05), and relative lung water content (p < 0.05). These increases were all significantly reduced (p < 0.05) by ICI 198,615 (bolus 15 mg/kg, infusion 15 mg/kg/h). Thrombin infusion caused a significant increase in myeloperoxidase activity in the lung tissue (p < 0.05). This increase was further accentuated by ICI 198,615, indicating that the effect of this antagonist is not due to reduction of leukocyte infiltration in the lungs. The results thus show that a leukotriene receptor antagonist effectively counteracts the increase in lung vascular permeability to protein caused by thrombin, and indicate that leukotrienes are important mediators of thrombin-induced pulmonary edema in the rat.

Animals↗
PubMed1995

Value of parents' estimates of children's developmental ages.

OBJECTIVE: To determine whether parents' estimates of children's developmental ages can function as a prescreening technique. DESIGN AND PARTICIPANTS: Parents of 234 children from birth to 77 months of age seeking well-child care in pediatric offices were queried in two separate studies. In the first study, parents were asked to give an estimate of their child's overall developmental age and, in the second study, to estimate ages in each of six developmental domains. Children were administered a range of screening measures of intelligence, speech-language, and adoptive behavior. RESULTS: The overall age-estimate, if less than chronologic age, was 75% sensitive to likely developmental problems and, if equal to or greater than chronologic age, was 90% specific in identifying children likely to have typical development. Age estimates for each developmental domain were 81% sensitive to likely developmental problems if less than chronologic age in the domains of fine motor, language, grass motor, or behavior, and 62% specific if equal to or greater than chronologic age. Estimates at or below chronologic age in receptive language or personal-social domains were 90% sensitive and 43% specific in identifying likely behavior problems. There were no differences in the accuracy of parents estimates on the basis of children's age, gender, race, parents' level of education, or parenting experience. CONCLUSION: Parents' overall age-estimates provided a sensitive and specific indicator of global developmental status, but insufficient information about strengths and weaknesses to enable focused referrals for services. In contrast, discrete patterns of age estimates in each developmental domain sensitively discriminated children with developmental versus behavioral problems, although specificity was limited. Age estimates appear to be a potentially helpful method for identifying a subset of children in need of thorough screening, although further research is needed on a larger sample given diagnostic rather than screening tests.

Adult↗
PubMed1995

Intrapericardial denervation: responses to water immersion in rhesus monkeys.

Eleven anesthetized rhesus monkeys were used to study cardiovascular, renal, and endocrine alterations associated with 120 min of head-out water immersion. Five animals underwent complete intrapericardial denervation using the Randall technique, while the remaining six monkeys served as intact controls. Each animal was chronically instrumented with an electromagnetic flow probe on the ascending aorta, a strain gauge pressure transducer implanted in the apex of the left ventricle (LV), and electrocardiogram leads anchored to the chest wall and LV. During immersion, LV end-diastolic pressure, urine flow, glomerular filtration rate, sodium excretion, and circulating atrial natriuretic peptide (ANP) each increased (P < 0.05) for intact and denervated monkeys. There were no alterations in free water clearance in either group during immersion, yet fractional excretion of free water increased (P < 0.05) in the intact monkeys. Plasma renin activity (PRA) decreased (P < 0.05) during immersion in intact monkeys but not the denervated animals. Plasma vasopressin (PVP) concentration decreased (P < 0.05) during the first 30 min of immersion in both groups but was not distinguishable from control by 60 min of immersion in denervated monkeys. These data demonstrate that complete cardiac denervation does not block the rise in plasma ANP or prevent the natriuresis associated with head-out water immersion. The suppression of PVP during the first minutes of immersion after complete cardiac denervation suggests that extracardiac sensing mechanisms associated with the induced fluid shifts may be responsible for the findings.

Animals↗
PubMed1995

Effect of indomethacin on thrombin-induced pulmonary edema in the rat.

The preventive effect of indomethacin on thrombin-induced pulmonary edema was studied in rats. Administration of thrombin caused a significant increase in lung weight, wet weight to dry weight ratio (WW/DW), and relative lung water content. During infusion of thrombin, mean pulmonary artery pressure rose and mean systemic artery pressure fell, PaO2 decreased progressively and there was a continuous rise in pH and PaCO2. An inhibitor of cyclooxygenase, indomethacin, at a dose of 1 mg/kg body weight, induced a significant further increase in lung weight (p < 0.05), and a tendency towards an increase in WW/DW and water content compared with animals given thrombin alone. Treatment with indomethacin, however, counteracted the elevated pulmonary artery pressure occurring in the early phase after thrombin infusion, but not that in the late phase. Systemic artery pressure was not affected by indomethacin. The increases in pH and PaCO2 after thrombin infusion were attenuated and remained stable almost at baseline level after indomethacin administration. Indomethacin did not prevent the hypoxemia induced by thrombin infusion. In conclusion, although indomethacin prevented the early increase in pulmonary artery pressure due to thrombin and the decrease in pH and the increase in PaCO2, it caused lung vascular permeability to protein to increase more than with thrombin alone.

Animals↗