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Biomedical subjects

J Williamson

Publications and source records attributed to J Williamson.

At least 91 records · Page 5Linked to original sources
PubMed1996

A global odds ratio regression model for bivariate ordered categorical data from ophthalmologic studies.

In typical clinical trials or epidemiologic studies of a bilateral eye disease, the primary outcome data consist of pairs of ordered categorical responses that tend to be highly correlated. In such studies, interest often centres in associating the outcome data with a grouping variable such as the treatment indicator or the exposure status and other person- and eye-specific covariates. In this paper, we propose a latent variable regression model to analyse such bivariate ordered categorical data. We use as a joint distribution for bivariate latent random variables the cross ratio distribution proposed by Plackett, which results in modelling the dependency between the fellow eyes with the global odds ratio. We illustrate the proposed model with data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy, a study that seeks to identify risk factors among younger-onset diabetics.

Age of Onset↗
PubMed1996

The gene encoding human intestinal trefoil factor (TFF3) is located on chromosome 21q22.3 clustered with other members of the trefoil peptide family.

The gene coding for human intestinal trefoil factor (hITF), a recently described cellular motogen produced by gastrointestinal goblet cells and epithelia elsewhere, is a member of the rapidly growing trefoil peptide family. In a rodent-human somatic cell hybrid panel, the hITF (HGMW-approved symbol TFF3) genomic locus segregated with human chromosome 21q. Fluorescence in situ hybridization with a 2.1-kb genomic probe of the hITF gene mapped this locus more precisely to the q22.3 region. Triple fluorescence in situ hybridization, together with physical mapping of human genomic DNA using pulsed-field gel electrophoresis, revealed that the hITF gene is tightly linked to those encoding the other known human trefoil peptides, namely the breast cancer estrogen-inducable gene pS2 (BCEI) and human spasmolytic polypeptide (hSP/SML1). This gene family could become a useful marker for the genetic and physical mapping of chromosome 21 and for a better definition of the region involved in the clinical phenotype of several genetic diseases.

Chromosome Mapping↗
PubMed1996

Functional changes in somatostatin and neuropeptide Y containing neurons in the rat hippocampus in chronic models of limbic seizures.

Using immunocytochemistry and in situ hybridization analysis of mRNA, we investigated the changes in the expression of somatostatin and neuropeptide Y (NPY) in the rat hippocampal principal neurons in kindling or after electrically induced status epilepticus (SE), two models of limbic epilepsy associated with different chronic sequelae of seizures and seizure-related neuropathology. At the preconvulsive stage 2 of kindling and after three consecutive tonic-clonic seizures (stage 5) but not after a single-discharge (AD), somatostatin and NPY immunoreactivity (IR) were markedly increased in interneurons of the deep hilus and the polymorphic cell layer and their presumed projections to the outer molecular layer of the dentate gyrus. Increased mRNA levels were observed in the same neurons. NPY IR and mRNA were highly expressed in pyramidal-shaped basket cells at both stages of kindling. IR was similar two days after stages 2 or 5 of kindling while less pronounced effects were observed one week after kindling completion. Peptide-containing neurons in the hilus appeared well preserved in spite of an average of 24% reduction of Nissl stained cells (p < 0.01) in the stimulated and contralateral hippocampus at stage 5. No sprouting of mossy fibres in the inner molecular layer was found as assessed by Timm staining. Thirty days after SE, somatostatin IR was slightly reduced or similar to controls in the ventral dentate gyrus and molecular layer in four or six rats (SE-I group) while in the two other post-SE rats (SE-II), somatostatin IR was lost. These changes were associated with a different extent of neurodegeneration as assessed by cell counting of Nissl stained sections. In the granule cells/mossy fibres NPY-IR was transiently expressed at stage 2 and after a single AD. Differently, NPY-IR was persistently enhanced in the mossy fibres of all post-SE rats particularly in the SE-II group. In these rats, NPY immunoreactive fibres were detected in the infrapyramidal region of the stratum oriens CA3 and in the inner molecular layer of the dentate gyrus very likely labeling sprouted mossy fibres. In the hippocampus proper of kindled rats, somatostatin and NPY IR were respectively enhanced in the stratum lacunosum moleculare, the subiculum and in the alveus while no significant changes were observed after SE. Changes in peptide expression were bilateral and involved both the dorsal and the ventral hippocampus. The lasting modifications in peptides IR and mRNA expression in distinct neuronal populations of the hippocampus may reflect functional modifications neurons and play a role in limbic epileptogenesis.

Animals↗
PubMed1996

Overutilization of acute-care beds in Veterans Affairs hospitals.

The authors tested the hypothesis that the Department of Veterans Affairs (VA) hospitals would have substantial overutilization of acute care beds and services because of policies that emphasize inpatient care over ambulatory care. Reviewers from 24 randomly selected VA hospitals applied the InterQual ISD* (Intensity, Severity, Discharge) criteria for appropriateness concurrently to a random sample of 2,432 admissions to acute medical, surgical, and psychiatry services. Reliability of hospital reviewers in applying the ISD* criteria was tested by comparing their reviews with those of a small group of expert reviewers. Validity of the ISD* criteria was tested by comparing the assessments of master reviewers with the implicit judgments of panels of nine physicians. The physician panels validated the ISD* admission criteria for medicine and surgery (74% agreement with master reviewers, kappa > 0.4), whereas the psychiatry criteria were not validated (66% agreement, kappa 0.29). Hospital reviewers reliably used all three criteria sets (> 83% agreement with master reviewers, kappa > 0.6). Rates of nonacute admissions to acute medical and surgical services were > 38% as determined by the hospital and master reviewers and by the physician panels. Nonacute rates of continued stay were > 32% for both medicine and surgery services. Similar rates of nonacute admissions and continued stay were found for all 24 hospitals. Reasons for nonacute admissions and continued stay included lack of an ambulatory care alternative, conservative physician practices, delays in discharge planning, and social factors such as homelessness and long travel distances to the hospital. Using criteria that the authors showed to be reliable and valid, substantial overutilization of acute medicine and surgical beds was found in a representative sample of VA hospitals. Correcting this situation will require changes in physician practice patterns, development of ambulatory care alternatives to inpatient care, and modification of current VA policies determining eligibility for care.

Acute Disease↗
PubMed1996

In vitro destruction of nerve cell cultures by Acanthamoeba spp.: a transmission and scanning electron microscopy study.

Trophozoites of 4 species of Acanthamoeba were cytopathic for cultured rat B103 neuroblastoma cells. Cytopathogenicity was evaluated by a chromium release assay and by transmission and scanning electron microscopy. Acanthamoeba culbertsoni, Acanthamoeba castellanii, and Acanthamoeba polyphaga destroyed B103 target cells at 37 C as evidenced by the release of radiolabel. Acanthamoeba astronyxis did not produce cytopathology at 37 C but destroyed nerve cells at 25 C. Transmission and scanning electron microscopy of cocultures maintained at different time periods revealed that all species of Acanthamoeba exhibited long cylindrical structures, termed digipodia, which made contact with target cells. Following this effector cell-target cell contact, membrane blebbing on the nerve cells was observed. These events were followed either by lysis of target nerve cells or ingestion of the target cells via food-cups and their subsequent channeling into intracytoplasmic food vacuoles. Use of the TUNEL (TdT-mediated dUTP nick end labeling) technique indicated that approximately 40% of B103 cells incubated with A. culbertsoni, 20% of B103 cells cocultured with A. castellanii or with A. polyphaga, and less than 1% of B103 cells incubated with A. astronyxis at 37 C were apoptotic after 24 hr of coculture. Studies using electron microscopy indicated that Acanthamoeba trophozoites destroyed nerve cells both by cytolysis and by ingestion of whole nerve cells via food-cups.

Acanthamoeba↗
PubMed1995

Use of monoclonal antibodies to cytochrome P450s to indicate the critical dealkylation and the P450s involved in methyl-n-amylnitrosamine mutagenicity in the presence of induced rat liver microsomes.

The mutagenicity for Salmonella typhimurium TA 1535 of the carcinogen methyl-n-amylnitrosamine (MNAN) was examined in the presence of rat liver microsomes from uninduced and induced rats. The number of mutations followed the order phenobarbital- and Aroclor-induced > 3-methylcholanthrene- and isoniazid-induced > uninduced microsomes. The MNAN metabolite 4-hydroxy-MNAN was not mutagenic. Using each type of induced liver microsomes, we examined the effect on MNAN mutagenicity of four monoclonal antibodies (MAbs) that inhibit cytochrome P450s. The MAbs inhibited MNAN mutagenicity in seven MAb-microsome combinations by up to 49%. Taken together, these results indicated that CYP (P450) 2B1/2B2 was responsible for one half and CYP 2C11 for one quarter of MNAN mutagenicity with phenobarbital-induced microsomes, CYP 1A1/1A2 accounted for about 40% of the mutagenicity with 3-methylcholanthrene-induced microsomes, CYP 2B1/2B2 accounted for half and CYP 1A1/1A2 and 2C11 for smaller proportions of the mutagenicity with Aroclor-induced microsomes, and CYP 1A1/1A2 accounted for about 30% of the mutagenicity with isoniazid-induced microsomes. With isoniazid-induced microsomes, MAb 2-66-3 to CYP 2B1/2B1 caused an unexpected 219% increase and MAb 1-68-11 caused a moderate increase in MNAN mutagenicity. The test MAbs also inhibited the microsome-catalyzed demethylation and depentylation of MNAN by up to 83%, confirming previous results. Four comparisons between individual mutagenic and metabolic results supported the view that depentylation of MNAN was more critical for its mutagenicity than was demethylation, e.g., with 3-methylcholanthrene- and Aroclor-induced microsomes, MAb 1-7-1 to CYP 1A1/1A2 inhibited mutagenesis and depentylation, but did not affect demethylation.

Animals↗
PubMed1995

Population management in an HMO: new roles for nursing.

A project to define and test population-management roles in nursing was implemented in a large HMO. Three patient populations were selected: diabetics, patients with multiple sclerosis, and pregnant adolescents. Expert nurse clinicians in each of the three areas piloted the role for six months, including establishing a system of care coordination for th populations. In all three pilots, patient care outcomes were improved. Keys to success included aligning the work with the critical clinical work of the organization, practicing in multidisciplinary settings, and reporting objective outcome data to constituents.

Adolescent↗
PubMed1995

Instrumentation and dosimeter-size artifacts in quantitative thermoluminescence dosimetry of low-dose fields.

Thermoluminescence dosimetry is extensively used for quantitative dose measurements in various irradiation fields such as dosimetry of brachytherapy sources. In this application, small doses on the order of 0.5 cGy must be accurately measured, which requires careful control of instrumentation, energy-dependence, and nonlinearity of detector response. Several investigators have observed the presence of some undesirable signals when the thermoluminescent dosimeters (TLDs) were read without any nitrogen gas flow in the TLD reader. Others have indicated that the "prereadout" annealing technique is the same as the "preirradiation" technique for doses above 10 cGy, but they have not extended their study to lower doses. The goal of this study is to investigate dependence of sensitivity and linearity of the TLD response to the flow of nitrogen gas in the TLD reader at low dose level, annealing technique, and TLD size. The effect of nitrogen flow sensitivity and linearity of two different sizes of lithium fluoride TLD-100 chips has been studied. Our data indicate a large standard deviation of TLD sensitivity, up to a factor of 2, when TLDs were read without nitrogen gas flow in the TLD reader. In addition, a large deviation from linearity was observed for doses below 5 cGy. When the reading-chamber was purged with nitrogen gas, dispersion of the responses of the TLDs that were exposed to the same dose fell to within 5%. At precision levels of 2% and 5%, the low dose limits are 1 cGy and 0.5 cGy, respectively, for large chips and 15 cGy and 1 cGy for small chips, if TLDs are read with nitrogen gas flow in the TLD reader.(ABSTRACT TRUNCATED AT 250 WORDS)

Artifacts↗
PubMed1995

The familial aggregation of obstructive sleep apnea.

An inherited basis for sleep-disordered breathing (SDB) has been suggested by reports of families with multiple affected members and by a previous study of the familial aggregation of symptoms of SDB. In this study, we quantify and characterize the aggregation of SDB and assess the degree to which familial similarities may be independent of obesity. This was a genetic-epidemiologic study that assessed the distribution of SDB in families identified through a proband with diagnosed sleep apnea and among families in the same community with no relative with known sleep apnea. SDB was assessed with overnight in-home monitoring of airflow, oxygen saturation, chest wall impedance, heart rate, and body movement. Standardized questionnaires were used to assess symptoms, and weight, height, and neck circumference were measured directly. Intergenerational and intragenerational correlation coefficients and pairwise odds ratios (ORs) were calculated with adjustment for proband sampling. In toto, 561 members of 91 families were studied: (1) 47 subjects with laboratory-confirmed SDB (index probands), (2) 44 community control subjects, and (3) the spouses and relatives of 1 and 2. Of all 91 families, 32 (35%) had two or more members with SDB, 30 (33%) had one affected member, and 29 had no affected members. SDB was more prevalent in the relatives of index probands (21%) than among neighborhood control subjects (12%) (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

The contribution of osteoarthritis to disability: preliminary data from the Women's Health and Aging Study.

Our objective was to examine the relationship of a self-reported physician diagnosis of arthritis with disability in elderly community dwelling women. Data from a representative sample of 1541 women aged 65 and above were analyzed to determine the prevalence and associations of a self-reported physician diagnosis of arthritis with other chronic conditions and difficulty performing physical activities. A history of physician diagnosed arthritis was reported by 902 (58.5%) women. Women with arthritis were significantly more likely to report fair or poor perceived health, as well as a physician diagnosis of angina, myocardial infarction, hypertension, diabetes, stroke, lung disease, and hearing and vision problems. After adjustment for age, race, education, marital status, and comorbid/geriatric conditions, arthritis was significantly associated with difficulty in the following 13 activities: raising arms, lifting < or = 10 pounds, walking 2-3 blocks, bathing or showering, climbing 10 steps, grasping, getting in or out of a bed or chair, dressing, using the toilet, preparing meals, doing personal shopping, heavy and light housework. We conclude that physician diagnosed arthritis is a common problem among elderly community dwelling women and is associated with difficulties in physical activity.

Activities of Daily Living↗
PubMed1994

Lp(a) concentrations and phenotypes in children with insulin-dependent diabetes mellitus.

Subjects with insulin-dependent diabetes mellitus (IDDM) have an increased incidence of coronary heart disease. Several studies have suggested that Lp(a) levels may be increased in IDDM subjects, although these studies have been limited by the lack of information on apo(a) phenotype and urinary albumin excretion. We compared Lp(a) concentrations in 66 children with IDDM and 18 non-diabetic children; all were non-Hispanic whites and none had detectable albuminuria. Lp(a) concentrations (mg/dl) were lower in subjects with IDDM than in non-diabetic subjects (12.0 +/- 2.2 vs. 20.0 +/- 6.1, respectively), although these means were not significantly different (P = 0.276). Postpubertal subjects, particularly males, had increased Lp(a) concentrations relative to prepubertal subjects (P = 0.041). Higher apo(a) molecular weight was associated with decreased Lp(a) concentrations in both diabetic and non-diabetic subjects. However, apo(a) size was not different in diabetic and non-diabetic subjects. Lp(a) concentrations were not significantly correlated with glycosylated hemoglobin levels in diabetic subjects (r = 0.11, P = NS). We also found similar Lp(a) concentrations in postpubertal IDDM subjects compared with adult non-Hispanic white non-diabetic subjects (n = 208) from the San Antonio Heart Study, a population-based study. These observations do not support increased Lp(a) concentrations in young normoalbuminuric IDDM subjects.

Adolescent↗
PubMed1994

Changes in glutamate receptor and proenkephalin gene expression after kindled seizures.

Changes in gene expression after kindled seizures were examined using microdissection of discrete brain areas and Northern and slot blot analyses. Experimental animals were kindled with either of two protocols: (1) a paradigm in which 50 Hz/10 s stimulus trains were delivered every 30 min through hippocampal electrodes (12 stimulations every other day for 4 days) and (2) a traditional approach in which 50 Hz/10 s stimulus trains were given to the hippocampus three times daily for 16 days. Rats were sacrificed 24 h or 30 days after the last kindled seizure. We first examined the possibility that kindling may affect transcription of mRNA for neurotransmitter receptors. We found significant decreases (22-58%) in AMPA/kainate activated glutamate receptor mRNAs (GluR1, -2, -3 mRNAs) in hippocampus, amygdala/entorhinal cortex and in frontoparietal cortex 24 h but not 30 days after rapidly kindled seizures. However, changes in GABA receptor alpha 1, alpha 2, alpha 4 or beta 1 mRNAs were not observed in any brain region 30 days after traditional kindling or 24 h after rapidly kindled seizures. In addition, we tested whether changes in the expression of proenkephalin could be detected after kindling. We found significant increases (1.7-10 fold) in proenkephalin mRNA in the frontoparietal cortex, hippocampus and in the amygdala/entorhinal cortex 24 h but not 30 days after rapidly kindled seizures. Our findings suggest that changes in glutamate receptor and proenkephalin gene expression are robust, acute sequelae to kindled seizures and may be involved in kindling.

Amygdala↗