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Biomedical subjects

M Weaver

Publications and source records attributed to M Weaver.

At least 19 recordsLinked to original sources
PubMed2006

Saccades in presymptomatic and early stages of Huntington disease.

OBJECTIVE: To evaluate quantitative measures of eye movements as possible biomarkers in prediagnostic and early stages of Huntington disease (HD). METHODS: The study sample (n = 215) included individuals both at risk and recently diagnosed with HD. All participants completed a uniform clinical evaluation which included administration of the Unified Huntington's Disease Rating Scale (UHDRS) by a movement disorder neurologist and molecular testing to determine HD gene status. A high resolution, video-based eye tracking system was employed to quantify measures of eye movement (error rates, latencies, SD of latencies, velocities, and accuracies) during a computerized battery of saccadic and steady fixation tasks. RESULTS: Prediagnostic HD gene carriers and individuals with early HD demonstrated three types of significant abnormalities while performing memory guided and anti-saccade tasks: increased error rate, increased saccade latency, and increased variability of saccade latency. The eye movement abnormalities increased with advancing motor signs of HD. CONCLUSIONS: Abnormalities in eye movement measures are a sensitive biomarker in the prediagnostic and early stages of Huntington disease (HD). These measures may be more sensitive to prediagnostic changes in HD than the currently employed neurologic motor assessment.

Eye Movements↗
PubMed2004

Economic evaluations of HIV treatment and health research with people diagnosed with HIV infection and co-occurring mental health and substance use disorders.

This paper describes the research challenges involved in measuring costs in economic evaluations of patients who are coping simultaneously with HIV/AIDS and co-occurring mental health and substance abuse disorders-especially in multi-site studies. We describe the general issues that arise in measuring costs for this population and suggest some operational solutions for their resolution, drawing from our experience in a recent multi-site health services research study focused on this population. We show that while reliance on patient self-report data may be unavoidable to provide a common denominator in multi-site studies, there are also some practical ways of improving the accuracy of such data and the cost estimates that result from them. We also provide readers with a means for securing the data collection instruments developed for the cost component of this study in the hope that these may serve as templates for researchers doing similar work.

Cost-Benefit Analysis↗
PubMed2003

Use of nuclear scintigraphy with 99mTc-HMPAO-labelled leucocytes to assess small intestinal malabsorption in 17 horses.

The diagnostic and prognostic value of nuclear scintigraphy with technetium-99m-labelled hexamethyl-propyleneamine oxime-labelled leucocytes was assessed in 17 horses with weight loss due to gastrointestinal malabsorption by comparing the results with the results obtained from 13 normal control horses. Intestinal uptake of activity was detected in 12 of the 17 cases but none of the control horses. The technique was therefore specific for intestinal pathology, but failed to detect some horses that might have had intestinal pathology. No indications of the horses' specific pathology were obtained, and their prognosis or response to treatment could not be predicted.

Animals↗
PubMed2003

Spinal manipulative therapy is an independent risk factor for vertebral artery dissection.

OBJECTIVE: To determine whether spinal manipulative therapy (SMT) is an independent risk factor for cervical artery dissection. METHODS: Using a nested case-control design, the authors reviewed all patients under age 60 with cervical arterial dissection (n = 151) and ischemic stroke or TIA from between 1995 and 2000 at two academic stroke centers. Controls (n = 306) were selected to match cases by sex and within age strata. Cases and controls were solicited by mail, and respondents were interviewed using a structured questionnaire. The medical records of interviewed patients were reviewed by two blinded neurologists to confirm that the patient had stroke or TIA and to determine whether there was evidence of arterial dissection. RESULTS: After interview and blinded chart review, 51 patients with dissection (mean age 41 +/- 10 years; 59% female) and 100 control patients (44 +/- 9 years; 58% female) were studied. In univariate analysis, patients with dissection were more likely to have had SMT within 30 days (14% vs 3%, p = 0.032), to have had neck or head pain preceding stroke or TIA (76% vs 40%, p < 0.001), and to be current consumers of alcohol (76% vs 57%, p = 0.021). In multivariate analysis, vertebral artery dissections were independently associated with SMT within 30 days (OR 6.62, 95% CI 1.4 to 30) and pain before stroke/TIA (OR 3.76, 95% CI 1.3 to 11). CONCLUSIONS: This case-controlled study of the influence of SMT and cervical arterial dissection shows that SMT is independently associated with vertebral arterial dissection, even after controlling for neck pain. Patients undergoing SMT should be consented for risk of stroke or vascular injury from the procedure. A significant increase in neck pain following spinal manipulative therapy warrants immediate medical evaluation.

Adult↗
PubMed2001

Cost-effectiveness of combined outreach for the pneumococcal and influenza vaccines.

BACKGROUND: We conducted a cost-effectiveness analysis as part of a randomized, controlled trial of a community-based outreach initiative to promote the pneumococcal and influenza vaccines for people aged 65 years or older. METHODS: The analysis was based on primary data from the trial on the increase in vaccination rates and cost of the intervention, and published estimates of the effectiveness of the vaccines and cost of treatment. We performed partial stochastic analyses based on the confidence intervals (CIs) of the effectiveness of the intervention and of the vaccines. RESULTS: The cost-effectiveness ratio of the combined-outreach initiative as implemented was $35 486 per quality-adjusted life-year (QALY), whereas it was $53 547 per QALY for the pneumococcal vaccine and $130 908 per QALY for the influenza vaccine. In partial stochastic analyses, the quasi-CI of the combined-outreach initiative ranged from $15 145 to $152 311 per QALY. The cost-effectiveness ratio of the intervention targeted to people who had never received the pneumococcal vaccine or who had not received the influenza vaccine in the previous year was $11 771 per QALY, with a quasi-CI of $3330 to $46 095 per QALY. With the use of the projected cost of replicating the intervention, the cost-effectiveness ratio was $26 512 per QALY for the initiative as implemented and $7843 per QALY for a targeted initiative. CONCLUSIONS: The community-based outreach initiative to promote the pneumococcal and influenza vaccines was reasonably cost-effective. Further improvements in cost-effectiveness could be made by targeting the initiative or through lessons learned during the first year that would reduce the cost of the initiative in subsequent years.

Aged↗
PubMed2001

Powerful ideas driven by simple tools: lessons from experimental embryology.

In developmental biology, as in all scientific fields, conceptual advances are tightly coupled to technological innovation. In this review, we trace the evolution of techniques in experimental embryology, from classical ablation to the latest methods utilizing in vivo electroporation, with lens induction as a linking theme.

Animals↗
PubMed2001

Reversal of tetraplegia in patients with cervical osteomyelitis--epidural abscess using anterior debridement and fusion.

OBJECTIVE: Aggressive anterior debridement and fusion has been advocated for the treatment of cervical osteomyelitis/epidural abscess (COEA) for many years. In this study we review our experiences with severely neurologically impaired (tetraplegic) patients with COEA. METHODS: From 1989-1999 we identified 20 cases of COEA treated with anterior debridement and fusion. Patients were identified from a prospectively maintained database. All inpatient and outpatient records were reviewed. Six patients were identified as being tetraplegic prior to surgery. Tetraplegia was defined as complete absence or only flicker movement of the extremities. RESULTS: The age range was 41 to 74. There were five men and one woman. Anterior corpectomy and fusion with either iliac crest auto- or allograft was performed in all patients. In four of six patients an anterior cervical plate was utilized for internal fixation. Four of six patients were ambulatory at last follow-up. CONCLUSION: Aggressive debridement and fusion in patients with COEA can result in successful outcomes even in patients who are tetraplegic prior to surgery.

Abscess↗
PubMed2001

Comparison of radiography and scintigraphy in the diagnosis of dental disorders in the horse.

Scintigraphy, with 99mTechnetium methylenediphosphonate (99mTc-MDP) and 99mTc-labelled leucocytes, was compared to radiography in the diagnosis of dental disease in the horse in a prospective case-controlled study, comprising 30 horses with clinical signs of dental disease and 30 control horses. In each case, right and left lateral, ventral and dorsal soft tissue and bone phase scintigraphic images were obtained after i.v. injection of 1 GBq/100 kg bwt 99mTc-MDP, using a gamma camera. The same views were acquired in 10 horses with clinical signs of dental disease and 12 control horses after injection of 99mTc-labelled leucocytes. Standard radiographic projections of the paranasal sinuses and of the apices of the maxillary and mandibular teeth were obtained. The scintigraphs and radiographs were assessed subjectively by 2 board-certified surgeons and one board-certified radiologist, with extensive experience of equine radiology, from who the clinical history was withheld. Sensitivity, specificity and kappa, as a measure of agreement, were calculated for the different methods. Bone phase images were also scored subjectively on a scale from 0 to 3 on the basis of isotope uptake over the teeth. Regions of interest were defined over the teeth, and normal teeth compared to diseased counterparts. Total scintigraphic counts were related to the age of the animal and to the disease process. Differences in density ratios between left and right teeth were evaluated using the Mann-Whitney Test. Dental disease was confirmed in 22 horses at surgery or postmortem examination. Horses with dental disease showed a significant increase in scintigraphic activity over the affected tooth compared to the contralateral tooth, with a typical pattern for different diseases. The sensitivity of scintigraphy with 99mTc-MDP proved to be excellent (95.5%), whereas the specificity was moderate (86.4%). In contrast, radiography had excellent specificity (95.0%) and a low sensitivity (51.5%). The greatest sensitivity and specificity were achieved by evaluating radiographs and scintigrams together. The objective scintigraphic density ratios were found to be significantly different between diseased and control horses. The results of this study suggest that, if a density ratio of 1.5 or greater between a suspected diseased tooth and its contralateral number is regarded as abnormal, only 1% false positive diagnoses and 20% false negative diagnoses will occur. In contrast, scintigraphy with 99mTc-labelled leucocytes was not very successful, due to the lack of anatomical detail provided by this technique, which made identification of the diseased tooth impossible. Accurate radiographic interpretation of dental disease presents difficulties, both in terms of missed diagnoses and mistaken diagnoses. Scintigraphy complements radiographic examination of dental structures by providing information important for accurate diagnosis and is, therefore, conceived to be essential for selection of the appropriate treatment for dental disease.

Animals↗
PubMed2001

Pim-1: a serine/threonine kinase with a role in cell survival, proliferation, differentiation and tumorigenesis.

Pim-1 belongs to a family of serine/threonine protein kinases that are highly conserved through evolution in multicellular organisms. Originally identified from moloney murine leukemia virus (MuLV)-induced T-cell lymphomas in mice, Pim-1 kinase is involved in the control of cell growth, differentiation and apoptosis. Expression of Pim-1 kinase can be stimulated by a variety of growth factors and regulated at four different levels: transcriptional, post-transcriptional, translational and post-translational. Several signal transduction pathways may be associated with the regulation of Pim-1's expression; accumulating data support that the expression of Pim-1 protein is mediated through activation of JAK/STATs. Recent studies of Pim family kinases indicate that Pim-1 kinase plays important roles outside of the hematopoietic system as well.

Animals↗
PubMed2000

Evidence that juvenile myelomonocytic leukemia can arise from a pluripotential stem cell.

Children with neurofibromatosis type 1 (NF1) carry germline mutations in one allele of the NF1 gene and are predisposed to myeloid malignancies, particularly juvenile myelomonocytic leukemia (JMML). Disruption of the remaining NF1 allele can be found in malignant cells. Flow cytometric cell sorting techniques to isolate the malignant cell populations and molecular genetic methods to assay for somatic loss of the normal NF1 allele were used to study an unusual child with NF1 and JMML who subsequently had T-cell lymphoma. The data show that malignant JMML and lymphoma cells share a common loss of genetic material involving the normal NF1 gene and approximately 50 Mb of flanking sequence, suggesting that the abnormal T-lymphoid and myeloid populations were derived from a common precursor cell. These data support the hypothesis that JMML can arise in a pluripotent hematopoietic cell.

Cell Differentiation↗
PubMed2000

Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in HdhQ92 and HdhQ111 knock-in mice.

Huntington's disease (HD) is caused by an expanded N-terminal glutamine tract that endows huntingtin with a striatal-selective structural property ultimately toxic to medium spiny neurons. In precise genetic models of juvenile HD, HdhQ92 and HdhQ111 knock-in mice, long polyglutamine segments change huntingtin's physical properties, producing HD-like in vivo correlates in the striatum, including nuclear localization of a version of the full-length protein predominant in medium spiny neurons, and subsequent formation of N-terminal inclusions and insoluble aggregate. These changes show glutamine length dependence and dominant inheritance with recruitment of wild-type protein, critical features of the altered HD property that strongly implicate them in the HD disease process and that suggest alternative pathogenic scenarios: the effect of the glutamine tract may act by altering interaction with a critical cellular constituent or by depleting a form of huntingtin essential to medium spiny striatal neurons.

Animals↗
PubMed2000

NF1 microdeletion breakpoints are clustered at flanking repetitive sequences.

Neurofibromatosis type 1 patients with a submicroscopic deletion spanning the NF1 tumor suppressor gene are remarkable for an early age at onset of cutaneous neurofibromas, suggesting the deletion of an additional locus that potentiates neurofibromagenesis. Construction of a 3.5 Mb BAC/PAC/YAC contig at chromosome 17q11.2 and analysis of somatic cell hybrids from microdeletion patients showed that 14 of 17 cases had deletions of 1.5 Mb in length. The deletions encompassed the entire 350 kb NF1 gene, three additional genes, one pseudogene and 16 expressed sequence tags (ESTs). In these cases, both proximal and distal breakpoints mapped at chromosomal regions of high identity, termed NF1REPs. These REPs, or clusters of paralogous loci, are 15-100 kb and harbor at least four ESTs and an expressed SH3GL pseudogene. The remaining three patients had at least one breakpoint outside an NF1REP element; one had a smaller deletion thereby narrowing the critical region harboring the putative locus that exacerbates neurofibroma development to 1 Mb. These data show that the likely mechanism of NF1 microdeletion is homologous recombination between NF1REPs on sister chromatids. NF1 microdeletion is the first REP-mediated rearrangement identified that results in loss of a tumor suppressor gene. Therefore, in addition to the germline rearrangements reported here, NF1REP-mediated somatic recombination could be an important mechanism for the loss of heterozygosity at NF1 in tumors of NF1 patients.

Female↗
PubMed2000

Years of productivity lost among injured workers in Washington state: modeling disability burden in workers' compensation.

BACKGROUND: Few studies have examined the impact of disability from nonfatal work-related injuries and illnesses. We developed Years of Productivity Lost (YPL) as a measure of the burden of disability. METHODS: YPL was calculated for incident workers' compensation claims with compensable injuries filed in 1986 in Washington State. Final work disability status was determined in June, 1993. We estimated YPL by adding actual accumulated time loss and future lost productivity predicted from permanent partial disability awards and pensions. RESULTS: Back and neck sprains were associated with the highest YPL followed by sprains of the lower and upper extremities. Using actual accumulated time loss, we calculated 14,624 years of productivity lost for compensable injuries in 1986. After including predicted lost productivity, YPL ranged from 28,017 to 33,502 years. CONCLUSIONS: YPL can be used to quantify the burden of disability due to occupational injuries and illnesses and to prioritize efforts to prevent long-term disability.

Absenteeism↗
PubMed2000

Splenosis presenting as occult gastrointestinal bleeding.

A 48-year-old man presented with recurrent gastrointestinal bleeding and anemia. Routine endoscopic evaluation was nondiagnostic. Angiography demonstrated multiple apparent arteriovenous malformations. Exploratory laparotomy revealed numerous splenic implants along the small and large bowels, some of which had apparently eroded through the bowel mucosa and bled. Excision of these penetrating lesions prevented further bleeding. An incidentally noted renal cell cancer was also resected. The patient's splenosis was the result of childhood trauma that caused splenic rupture and precipitated splenectomy. Splenosis develops frequently following traumatic splenic rupture. Experimental evidence suggests that the presence of an intact spleen suppresses the growth and development of splenic implants. Following splenectomy, splenules may replace some of the "housekeeping" and immunologic functions of the spleen, but even patients with documented splenosis should be considered functionally hyposplenic. While in most cases splenules cause no symptoms, splenosis must be considered in the differential diagnosis of previously splenectomized patients who present with unexplained masses or occult bleeding.

Diagnosis, Differential↗
PubMed2000

Knowledge and opinions about organ donation among urban high school students: pilot test of a health education program.

BACKGROUND: Increasing the diversity of the organ donor pool might improve the opportunities for people of color on organ transplant waiting lists to receive donated organs. We report on the results of a pilot classroom health education program to improve knowledge about organ donation and transplantation among a diverse student body at an urban high school. METHODS: The effectiveness of the educational program was evaluated with baseline and follow-up questionnaires which examined: 1) whether the program increased knowledge about organ donation; 2) whether the students' opinions about organ donation changed; and 3) whether the program was related to any changes in opinion. RESULTS: On the follow-up questionnaire, correct answers on 15 factual questions increased by 18% for the treatment group, compared to 5% for the control group (p = 0.00). Regarding opinions, at baseline 92% of white students had positive opinions about donation, compared to 48% of the students of color (p = 0.00). In the follow-up survey, the increase in positive opinions among the students of color was significantly greater than among white students (p = 0.04). In this pilot study, however, changes in opinions occurred with equal frequency among students in the treatment and control groups. In regression analysis, both knowledge of the subject and discussing donation with one's family were significantly associated with positive opinions about donation. CONCLUSIONS: Overall, this pilot study provided encouraging evidence that the classroom health education program affected knowledge about organ donation, and that opinions about organ donation are responsive to increases in knowledge.

Adolescent↗
PubMed2000

Refined mapping of the human serotonin transporter (SLC6A4) gene within 17q11 adjacent to the CPD and NF1 genes.

The SLC6A4 gene encodes the serotonin transporter, the target of an important class of antidepressant drugs (serotonin selective reuptake inhibitors). Polymorphisms in the SLC6A4 gene have been reported to be associated with susceptibility to depression and other psychiatric disorders. We have constructed a 1 Mb YAC and PAC contig which harbours both the SLC6A4 and the carboxypeptidase D (CPD) genes. The order of loci within the contig was cen-D17S975-D17S1549-24R-D17S1294-SLC6A4-28L+ ++-(CPD, D17S2009, D17S2004)-D17S2120-ter. Both genes were deleted in one of 17 neurofibromatosis type 1 (NF1) patients carrying submicroscopic NF1 contiguous gene deletions.

Carboxypeptidases↗
PubMed2000

Bmp4 and Fgf10 play opposing roles during lung bud morphogenesis.

Morphogenesis of the mouse lung involves reciprocal interactions between the epithelial endoderm and the surrounding mesenchyme, leading to an invariant early pattern of branching that forms the basis of the respiratory tree. There is evidence that Fibroblast growth factor 10 (Fgf10) and Bone Morphogenetic Protein 4 (Bmp4), expressed in the distal mesenchyme and endoderm, respectively, play important roles in branching morphogenesis. To examine these roles in more detail, we have exploited an in vitro culture system in which isolated endoderm is incubated in Matrigel(TM) substratum with Fgf-loaded beads. In addition, we have used a Bmp4(lacZ) line of mice in which lacZ faithfully reports Bmp4 expression. Analysis of lung endoderm in vivo shows a dynamic pattern of Bmp4(lacZ) expression during bud outgrowth, extension and branching. In vitro, Fgf10 induces both proliferation and chemotaxis of isolated endoderm, whether it is derived from the distal or proximal lung. Moreover, after 48 hours, Bmp4(lacZ) expression is upregulated in the endoderm closest to the bead. Addition of 30-50 ng/ml of exogenous purified Bmp4 to the culture medium inhibits Fgf-induced budding or chemotaxis, and inhibits overall proliferation. By contrast, the Bmp-binding protein Noggin enhances Fgf-induced morphogenesis. Based on these and other results, we propose a model for the combinatorial roles of Fgf10 and Bmp4 in branching morphogenesis of the lung.

Animals↗