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Communication↗
Biomedical subjects
S Larson
Publications and source records attributed to S Larson.
Malignant schwannoma of the parapharyngeal space.
We present a case of malignant schwannoma (MS) of the parapharyngeal space which completely encircled the internal carotid artery in close proximity to the skull base and required resection of the internal carotid artery along with the excision of the tumour. There have been three previous case reports in the literature of malignant schwannoma of the parapharyngeal space of which one case was associated with neurofibromatosis. Our patient did not exhibit any feature of neurofibromatosis.
Adult↗
The role of animal science in natural resource management: current decision making models and future needs.
Sustainable systems for land and natural resource management must be biologically, economically, and socially sustainable. Scientists and educators have historically viewed their role as developing new knowledge and technology to enhance biological and economic sustainability. Scientists have traditionally viewed sociopolitical sustainability and policy development as beyond our appropriate roles. Changing public values and perceptions on appropriate land use and natural resource protection are forcing land grant universities and their scientists and educators to re-evaluate traditional paradigms. The animal science community, in concert with the social and other biological sciences, must become more proactive in decision making processes on appropriate land use and natural resource management if we are to remain relevant. This paper describes the current situation and outlines approaches for the research and education communities to be important contributors to collaborative decision making processes on land and natural resource management.
Animal Husbandry↗
A process for developing a rural training track.
BACKGROUND AND OBJECTIVES: This article describes the process used by the University of Wisconsin-Madison Family Practice Residency Program to establish its first rural training track (RTT) in Baraboo, Wis. The process includes 1) establishing a core planning group to develop rural site selection criteria with specifications on distance traveled, faculty composition, teaching commitment, rural hospital capabilities, and availability of subspecialty teaching, 2) involvement of the state Area Health Education Center, 3) budget planning, 4) telecommunications plans, including e-mail, library search, and Internet connectivity, 5) creation of a residency curriculum in collaboration with the rural site's faculty and staff, 6) preparing an accreditation document to submit to the Residency Review Committee, and 7) faculty development programs for rural faculty. The program then participates in the National Residency Matching Program with an independent Match number.
Accreditation↗
Purkinje cell expression of a mutant allele of SCA1 in transgenic mice leads to disparate effects on motor behaviors, followed by a progressive cerebellar dysfunction and histological alterations.
Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurological disorder caused by the expansion of a CAG repeat encoding a polyglutamine tract. Work presented here describes the behavioral and neuropathological course seen in mutant SCA1 transgenic mice. Behavioral tests indicate that at 5 weeks of age mutant mice have an impaired performance on the rotating rod in the absence of deficits in balance and coordination. In contrast, these mutant SCA1 mice have an increased initial exploratory behavior. Thus, expression of the mutant SCA1 allele within cerebellar Purkinje cells has divergent effects on the motor behavior of juvenile animals: a compromise of rotating rod performance and a simultaneous enhancement of initial exploratory activity. With age, these animals develop incoordination with concomitant progressive Purkinje neuron dendritic and somatic atrophy but relatively little cell loss. Therefore, the eventual development of ataxia caused by the expression of a mutant SCA1 allele is not the result of cell death per se, but the result of cellular dysfunction and morphological alterations that occur before neuronal demise.
Alleles↗
Screening for the mitochondrial DNA A3243G mutation in children with insulin-dependent diabetes mellitus.
Since recent studies demonstrated the occurrence of the mitochondrial DNA (mtDNA) mutation A3243G in patients with adult-onset diabetes, an investigation was undertaken to determine the frequency of this mutation in a pediatric population with insulin-dependent diabetes mellitus (IDDM). DNA was extracted from peripheral blood of 270 pediatric patients with IDDM. The presence of the mtDNA A3243G mutation was screened for by minisequencing and mutation-specific ApaI endonuclease restriction after polymerase chain reaction (PCR) amplification of mtDNA. The A3243G mtDNA mutation was not found in any IDDM patients examined. This mutation is uncommon in children with IDDM from various ethnic and racial groups. Therefore, the contribution of the mutation to the pathogenesis of IDDM, if any, is minimal.
Adolescent↗
Pharmacokinetics and acute toxicology of intraventricular 131 I-monoclonal antibody targeting disialoganglioside in non-human primates.
Tumors metastatic to the leptomeninges are often incurable despite current aggressive treatment modalities. Regional therapy by intrathecal administration of monoclonal antibodies (MoAbs) can maximize their concentration to tumor sites while reducing systemic toxicities. Anti-GD2 antibody 3F8 has successfully targeted human neuroectoderm derived tumors. Disialoganglioside GD2 expression in the central nervous system is identical between humans and cynomolgus monkeys. We studied the pharmacokinetics and the acute and subacute toxicities of intraventricular 131I-3F8 in 8 cynomolgus monkeys. Four animals were purposely immunized with intravenous 3F8 administered 2-4 weeks prior to injections. All animals remained clinically stable. Toxicities included weight loss, fever and CSF leukocytosis. One animal developed a left-sided hemiparesis following his seventh injection, presumably due to a local drug accumulation in the setting of an intermittently patent catheter. The estimated radiation dose to the CSF was 19-48 Gy in the immunized monkeys and 19-82 Gy in the nonimmunized monkeys, and to blood was 0.11-0.98 Gy and 0.29-2.03 Gy, respectively. Histopathology revealed chronic reactive changes adjacent to the region of catheter placement and a focal vasculitis in 2 animals. Peripheral blood counts and bone marrow examinations remained normal. Because of the blood-brain barrier, CSF monkey-anti-mouse antibody titers were less than 10 per cent of those in the serum. In contrast to the CSF radioactivity clearance which was similar in all animals, blood clearance was substantially accelerated in 3F8-immunized animals versus controls. Correspondingly, the CSF to blood dose ratio was improved 1.3 to 6.6 fold (mean 3.5). We conclude that intraventricular administration of 131I-3F8 in primates is tolerable. It can deliver very high doses of radiation to the CSF space with minimal toxicity to blood and bone marrow. Serum anti-mouse antibody accelerates the clearance of 131I-3F8 in blood and may improve the therapeutic index.
Animals↗
Noninvasive imaging of herpes virus thymidine kinase gene transfer and expression: a potential method for monitoring clinical gene therapy.
Noninvasive imaging of herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene expression is possible with a clinical gamma camera and by single-photon emission tomography (SPECT) using 131I-labeled 2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodo-uracil (FIAU). Studies were performed in rats bearing s.c. tumors. Tumors were produced by injection of wild-type RG2 glioma or W256 mammary carcinoma cells into one flank and RG2TK+ glioma or W256TK+ mammary carcinoma cells (that had been transduced in vitro with the HSV1-tk gene) into the opposite flank. In some animals, HSV1-tk gene transduction of the pre-established wild-type tumors was accomplished in vivo by direct intratumoral injection of retroviral vector-producer cells. Imaging studies were performed 2 weeks after tumor transduction to allow time for production and spread of the retroviruses through the tumor and for sufficient growth and increase in size of the tumors to facilitate imaging. The gamma camera and SPECT images revealed highly specific localization of [131I]FIAU-derived radioactivity to areas of HSV1-tk gene expression at 24, 36, and 48 h after i.v. administration of 1.6-2.8 mCi of [131I]FIAU. Comparative analysis of quantitative autoradiographic images obtained from the same tumors confirmed that the high levels of [131I]FIAU-derived radioactivity (> 1% dose) were localized to areas of HSV1-tk gene expression demonstrated by immunohistochemical staining for HSV1-tk protein. In contrast, significantly lower levels of [131I]FIAU-derived radioactivity (< 0.01%) were observed in the surrounding nontransduced tumor tissue, contralateral wild-type tumors, and other tissues that showed no immunohistochemical staining for the HSV1-tk protein. The magnitude of FIAU accumulation in RG2TK+, W256TK+, and wild-type tumors corresponded to the in vitro ganciclovir sensitivity of the cell lines used to produce these tumors, which indicates that the magnitude of FIAU accumulation reflects the level of HSV1-tk gene expression. We suggest that "clinically relevant" levels of HSV1-tk gene expression in transfected tissue can be imaged with [131I]FIAU and a gamma camera or SPECT, and that a significant improvement in imaging sensitivity and resolution is expected with [124I]FIAU and PET.
Animals↗
Anti-islet autoantibodies detected by monoclonal antibody 1A2: further studies suggesting a role in the pathogenesis of IDDM.
Insulin-dependent diabetes mellitus (IDDM) is associated with autoantibodies to several pancreatic islet antigens. We have described an assay in which autoantibodies displace a radiolabelled monoclonal anti-islet antibody. Sera from 87% of 429 children at time of diagnosis of IDDM were positive, while sera from control groups had much lower prevalences (1.3-19%). Sera from 41.9% of diabetic subjects remained positive after 20 years duration of IDDM. Sera from 23.6% of parents and 37.9% of non-diabetic siblings were positive. Twenty relatives who subsequently developed IDDM had the same prevalence of the antibodies (85%) as did the patients at time of diagnosis. These findings confirm that the autoantibodies detected by monoclonal antibody (mAb) 1A2 are common at the onset of IDDM and their presence prior to the onset of hyperglycaemia suggests that this method may be useful in screening non-diabetic populations. The high prevalence of antibodies in relatives reduces the efficacy for diabetes prediction, but suggests either that generation of these antibodies is an autosomal dominant trait, or that the antigen detected by these antibodies is cross-reactive with a common environmental antigen. Differentiation between these hypotheses will await the identification of the specific islet-cell antigen detected by mAb 1A2.
Adolescent↗
Use of praziquantel for the control of Moniezia expansa in lambs.
The efficacy of a drench containing praziquantel in combination with levamisole was evaluated in four trials performed in the 1990-91 and 1992-93 seasons in the Waikato Region of New Zealand. The trials involved 93 naturally infected lambs and compared the efficacy of a 3.75 mg/kg praziquantel 7.5mg/kg levamisole drench against Moniezia expansa, with albendazole, an albendazole-levamisole combination and oxyclozanide-levamisole combination in controlled trials. There was no significant reduction in the number of Moniezia expansa scoleces or proglottids in the control, albendazole and albendazole-levamisole groups. Oxyclozanide gave a high clearance of proglottids, but a 28% reduction of scoleces. The praziquantel-levamisole combination demonstrated complete removal of segments in all trials, and of scoleces in two trials. One scolex was found in each of the two other trials. The combination was also tested for efficacy against nematode parasites. Total worm counts indicated that levamisole in the praziquantel-levamisole combination drench retained its efficacy. The economic benefits of the use of the praziquantel-levamisole drench were investigated. This trial compared the liveweight gains of three groups of 100 lambs treated twice 4 weeks apart with either levamisole or with the praziquantel-levamisole combination or acting as untreated control group. The group treated with the praziquantel-levamisole combination gained significantly more weight in both 4-week periods and overall, when compared with either the control or levamisole treated animals.
Journal Article↗
Continuous quality improvement for peritoneal dialysis patients.
In addition to a significant savings in time, several qualitative factors were impacted positively by this change in practice. Clear guidelines provided a structure that both physicians and nursing supported, thereby improving their relationship. The LPN's role was amended to include the stop-and-start procedure, which enhanced their self-esteem. Having the assistive personnel contribute to the dialysis regimen allowed the RN more latitude in managing patient care and efficient use of time. Because the procedure was now done more efficiently, therapy was initiated without delay. Lastly, patients expressed satisfaction because the nursing staff's own technique and the patient was now being discharged without their own technique and the patient was now being discharged without delay. All RN and LPN staff continue to be trained in the procedure. Cases of peritonitis continue to be investigated with favorable results. Results of this project were shared not only with the staff but also with the management committee of the hospital. Management had embraced the philosophy of continuous QI. The management committee was anxious to see the principles of continuous QI improve efficiency and patient outcomes. Reducing the complexity and decreasing the time required for the procedure maintained quality patient outcomes. Applying the continuous quality monitoring process and tools to the management of one group of chronically ill patients was shown to be an effective means of improving patient care and efficiency as well as of reducing costs.
Academic Medical Centers↗
The genome reconstruction manager: a software environment for supporting high-throughput DNA sequencing.
A new software system designed for use in high-throughput DNA sequencing laboratories is described. The Genome Reconstruction Manager (GRM) was developed from requirements derived from ongoing large-scale DNA sequencing projects. Object-oriented principles were followed in designing the system, and tools supporting object-oriented system development were employed for its implementation. GRM provides several advances in software support for high-throughput DNA sequencing: support for random, directed, and mixed sequencing strategies; a novel system for fragment assembly; a commercial object data-base management system for data storage; a client/server architecture for using network computational servers; and an underlying data model that can evolve to support fully automatic sequence reconstruction. GRM is currently being deployed for production use in high-throughput DNA sequencing projects.
Algorithms↗
[Warning against routine use of heart surgery. Safety and quality are at risk].
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Cardiac Surgical Procedures↗
Tracer imaging in lung cancer.
Lung cancer is the leading cause of death from cancer in males. Adequate staging is essential if proper treatment is to be administered. Current morphological imaging modalities are confronted with problems in the staging of lung cancer, in the evaluation of treatment response, and in establishing whether a residual mass is due to fibrosis, residual tumors or local recurrence. Nuclear medicine imaging techniques have advanced from planar gallium-67 citrate scans in the 1970s to multihead-detector single-photon emission tomography for 67Ga, Thallium-201 chloride, technetium-99m SestaMIBI, monoclonal antibodies, and octreotide compounds. Results of positron emission tomography (PET) with fluorine-18 deoxyglucose or carbon-11 methionine are very promising. PET units are now employed in centers all over the world and the recently introduced whole-body PET units will be ideal for the correct staging of malignant diseases. The current status of various nuclear medicine imaging procedures is reviewed. The problems and advantages of each scintigraphic procedure are discussed. It appears that many of the problems that confront morphological imaging will be solved by nuclear medicine techniques in the future.
Aged↗
The effect of midazolam on median nerve somatosensory evoked potentials.
OBJECTIVE: To quantify the effect of an induction dose of midazolam on median nerve somatosensory evoked potentials. METHODS: We studied 10 patients undergoing lumbar spine surgery. After an induction dose of intravenous midazolam was given, MNEPs were collected for ten minutes. After ten minutes the patients were intubated and their anesthetic was supplemented with 0.5% isoflurane, narcotic, and N2O. RESULTS: We found a clinically significant decrease in amplitude and an insignificant delay in latency. CONCLUSION: When midazolam is used as an anesthetic induction agent, a decrease in amplitude can be expected.
Adolescent↗
Determination of airborne cadmium in environmental tobacco smoke by instrumental neutron activation analysis with a compton suppression system.
Concentrations of cadmium, a toxic trace element, were measured in the indoor air of several public places where environmental tobacco smoke was present. Particulate-phase cadmium concentrations were determined by analyzing air filter samples using epithermal instrumental neutron activation analysis in conjunction with a Compton suppression gamma-ray detection system, in which the detection limit for cadmium was reduced to a few nanograms per filter. A cascade impactor and a personal filter sampler were used to collect the indoor suspended particulate matter for size-fractionated mass as well as total mass, respectively. Results show that where environmental tobacco smoke is present, cadmium concentrations are significantly higher than background and that about 80% of the cadmium found in indoor airborne particulate matter is associated with particles with aerodynamic diameters less than 1.8 microns. In one instance, airborne cadmium concentrations in a music club were found to be 38 ng/m, which is at least 30 times higher than background.
Air Pollutants↗
Special motto enforces the importance of humor and hugs.
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Hospital Units↗
NR-LU-10 monoclonal antibody scanning. A helpful new adjunct to computed tomography in evaluating non-small-cell lung cancer.
UNLABELLED: Computed tomographic scanning has improved the noninvasive staging of lung cancer but has the deficiency of not distinguishing benign from malignant lesions. This prospective trial evaluated the usefulness of a new radiolabeled monoclonal antibody, NR-LU-10, as an adjunct to computed tomography by assessing its clinical applicability and accuracy in detecting malignancy in primary lung tumors and mediastinal nodes. NR-LU-10 is a technetium 99m-labeled Fab fragment of a murine immunoglobulin G2b monoclonal antibody that recognizes a 40 kD glycoprotein expressed in lung and other epithelial cancers. METHODS: (1) Patients with potentially resectable non-small-cell lung cancer were eligible; (2) all patients had computed tomographic scans of the chest; (3) whole body and single photon emission computed tomographic imaging were performed 14 to 17 hours after intravenous infusion of 20 to 30 mCi of NR-LU-10; (4) subsequent mediastinoscopy or thoracotomy with complete mediastinal nodal mapping provided pathologic correlation. RESULTS: Twenty-four patients were entered, 14 men and 10 women. No allergic reactions or other adverse effects were seen. Interference from a prior ventilation-perfusion scan precluded adequate imaging in 1 patient, but high-quality images were obtained in the other 23 patients. The 22 primary malignant tumors all had uptake and there was no uptake in 1 lung nodule found to be benign. In 21 patients who had surgical correlation of mediastinal nodal involvement, NR-LU-10 was false-positive in 5 and false-negative in 1; results of computed tomography were false-positive in 6 and false-negative in 1. In this preliminary study, NR-LU-10 antibody scanning was safe and easily performed, it produced high-quality images of the lung and mediastinum, and it was accurate in detecting primary non-small-cell lung cancers. Further evaluation of its value in staging the mediastinum is needed, in particular, its role as an adjunct to computed tomography to help distinguish benign from malignant lesions.
Antibodies, Monoclonal↗