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Biomedical subjects

J Hall

Publications and source records attributed to J Hall.

At least 37 records · Page 2Linked to original sources
PubMed2000

A pilot study of amygdala volumes in pediatric generalized anxiety disorder.

BACKGROUND: The neurodevelopment of childhood anxiety disorders is not well understood. Basic research has implicated the amygdala and circuits related to these nuclei as being central to several aspects of fear and fear-related behaviors in animals. METHODS: Magnetic resonance imaging was used to measure amygdala volumes and comparison brain regions in 12 child and adolescent subjects with generalized anxiety disorder and 24 comparison subjects. Groups were matched on age, sex, height, and handedness and were also similar on measures of weight, socioeconomic status, and full scale IQ. RESULTS: Right and total amygdala volumes were significantly larger in generalized anxiety disorder subjects. Intracranial, cerebral, cerebral gray and white matter, temporal lobe, hippocampal, and basal ganglia volumes and measures of the midsagittal area of the corpus callosum did not differ between groups. CONCLUSIONS: Although these data are preliminary and from a small sample, the results are consistent with a line of thinking that alterations in the structure and function of the amygdala may be associated with pediatric generalized anxiety disorder.

Adolescent↗
PubMed2000

Induction of apoptosis in lung-cancer cells following bcl-xL anti-sense treatment.

Over-expression of the anti-apoptotic protein bcl-xL is frequently found in lung cancer where it potentially contributes to tumor development, progression and drug resistance. To override the apoptotic block in lung-adenocarcinoma and small-cell-lung-cancer (SCLC) cells caused by over-expression of bcl-xL, an anti-sense oligodeoxynucleotide was designed targeting a sequence unique to the bcl-xL coding region and not shared by the pro-apoptotic splice variant bcl-xS. Moreover, to improve the biophysical properties of the anti-sense compound, 2;-methoxy-ethoxy modifications were made to selected deoxy-ribose residues. The resulting gapmer oligonucleotide 4259 was tested on lung-adenocarcinoma and SCLC cell lines in vitro. Treatment of the adenocarcinoma cell lines A549 and NCI-H125 and the SCLC cell lines SW2 and NCI-H69 with 600 nM 4259 reduced bcl-xL levels by 70 to 90%. In the lung-adenocarcinoma cell lines, apoptosis was induced, as indicated by caspase-3-like protease activation and nuclear condensation and fragmentation. In contrast, in the SCLC cell lines, no induction of apoptosis could be demonstrated. These findings imply that bcl-xL is a more critical survival factor for lung adenocarcinomas than for SCLC, and suggest the use of oligonucleotide 4259 for therapy of this major sub-type of lung cancer.

Apoptosis↗
PubMed2000

Clinical anatomy of the popliteal blood vessels.

The surgical management of venous injuries in the popliteal fossa is a contested issue. The basic options are ligation or repair. Most anatomy textbooks briefly describe a single popliteal vein, and the literature contains few references on venous patterns in this region. Although the primary objective of this study was to analyze venous variability in 52 dissected cadaveric popliteal fossae and 63 venograms, data were also collected on the popliteal artery. Nine groups (A-I) were designated regarding the manner of formation of the popliteal vein. These groupings were based primarily on differences in the union of the anterior tibial, posterior tibial, and fibular (peroneal) veins to form medial and lateral (popliteal) veins, and whether these two veins fused to form a singular popliteal vein proximal or distal to the transverse plane at the level of the distal edge of the femoral condyles (FC). In the majority of the dissections and venograms, multiple veins crossed the FC, and the medial vein was larger in diameter than the lateral vein. Two patterns of popliteal artery termination were observed based on differences in the site of origin of the fibular artery. The results were compared with anatomy and vascular surgery textbook descriptions and sparse literature reports on vascular variations in the popliteal fossa. It is hoped that these data will benefit surgeons performing procedures in this region.

Cadaver↗
PubMed2000

Reaction of mock jurors to testimony of a court appointed expert.

A study was conducted to assess the impact of court appointed experts on the judgments of mock jurors. A civil proceeding was adopted for the experiment. Mock jurors heard testimony about a plaintiff's injury in an automobile accident. In some conditions, medical testimony for the plaintiff and defendant was provided by experts hired by each side. In other conditions, a medical expert appointed by the court testified in addition to the two adversarial experts. In one of these conditions, the court expert sided with the plaintiff; in another, the expert sided with the defendant. The plaintiff in the case was always an individual. The defendant was sometimes a corporation and sometimes an individual. The results showed that mock jurors sided with the court appointed expert in every condition except when the expert favored a corporate defendant. The results were discussed in terms of heuristic processing of persuasive information.

Criminal Law↗
PubMed2000

Distributive justice in Medicaid capitation: the evidence from Colorado.

In 1995, the state of Colorado began a new funding program for the provision of mental health services to Medicaid recipients. Medicaid funding was restructured from a fee-for-service system into a capitated managed care system. The restructuring altered the way in which mental health resources were allocated within Colorado's mental health system. This article explores the ethical principles inherent in the allocation of mental health resources within Colorado. The allocation system before and after the capitation pilot is analyzed according to three models of distributive justice. Under capitation, access to care corresponds to egalitarian ideals, while service delivery and outcomes follow a more utilitarian philosophy. Results from several empirical studies of the Colorado Medicaid system are used to support this ethical analysis. The analysis leads to the suggestion that the fair-opportunity rule may be a useful principle for developing just distribution systems in other states in the future.

Capitation Fee↗
PubMed2000

The ATM gene and breast cancer: is it really a risk factor?

The genetic determinants for most breast cancer cases remain elusive. Whilst mutations in BRCA1 and BRCA2 significantly contribute to familial breast cancer risk, their contribution to sporadic breast cancer is low. In such cases genes frequently altered in the general population, such as the gene mutated in Ataxia telangiectasia (AT), ATM may be important risk factors. The initial interest in studying ATM heterozygosity in breast cancer arose from the findings of epidemiological studies of AT families in which AT heterozygote women had an increased risk of breast cancer and estimations that 1% of the population are AT heterozygotes. One of the clinical features of AT patients is extreme cellular sensitivity to ionising radiation. This observation, together with the finding that a significant proportion of breast cancer patients show an exaggerated acute or late normal tissue reactions after radiotherapy, has lead to the suggestion that AT heterozygosity plays a role in radiosensitivity and breast cancer development. Loss of heterozygosity in the region of the ATM gene on chromosome 11, has been found in about 40% of sporadic breast tumours. However, screening for ATM mutations in sporadic breast cancer cases, showing or not adverse effects to radiotherapy, has not revealed the magnitude of involvement of the ATM gene expected. Their size and the use of the protein truncation test to identify mutations limit many of these studies. This latter parameter is critical as the profile of mutations in AT patients may not be representative of the ATM mutations in other diseases. The potential role of rare sequence variants within the ATM gene, sometimes reported as polymorphisms, also needs to be fully assessed in larger cohorts of breast cancer patients and controls in order to determine whether they represent cancer and/or radiation sensitivity predisposing mutations.

Ataxia Telangiectasia Mutated Proteins↗
PubMed2000

Where the girls (and women) are.

This paper takes up a theoretical and empirical investigation of how two community-based projects for young women both create safety from community and domestic violence but how, in the process, discourses of multicultural inclusion define one site, and racist discourses of exclusion float through the other site. By relying on two intensive qualitative case studies of community-based organizations for girls, one exclusively White and working class and the other expressly multicultural and antiracist, we try to identify those structures and practices that support feminist, but inadvertently racist, work and those structures and practices that enable, at once, feminist and antiracist consciousness and praxis.

Adolescent↗
PubMed2000

Quality of life three months and one year after first treatment for early stage breast cancer: influence of treatment and patient characteristics.

This paper reports the quality of life (QoL) of a large cohort of Australian women three and twelve months after surgery for early stage breast cancer (ESBC), and shows that the impact of disease and treatment on QoL differed by age, education and marital status. Eighty-three percent of eligible patients were recruited; 86% had breast conserving surgery and 14% mastectomy. Response rates were 93% (n = 305) at three months and 88% (n = 291) at one year. Quality of life was measured with the EORTC core questionnaire (QLQ-C30) and an ESBC-specific questionnaire. Multilevel analysis was used to estimate the effects and interactions of time, treatment and patient characteristics. Most symptoms declined between three months and one year, but arm and menopausal symptoms persisted. Emotional, social and role functioning improved over time, and fear of disease recurrence diminished. Younger women faired worse than older women on a broad range of QoL dimensions. Single women and those with less education faired worse on a number of dimensions. The negative impact of mastectomy on body image was greatest among married women, particularly young married women. These sociodemographic distinctions are relevant when discussing treatment options with women facing a diagnosis of ESBC.

Adult↗
PubMed2000

Rapid and selective induction of BDNF expression in the hippocampus during contextual learning.

The hippocampus is required for many forms of long-term memory in both humans and animals, and formation of long-lasting memories requires the synthesis of new proteins. Furthermore, the long-term potentiation (LTP) of hippocampal synapses, a widely studied model of memory, also depends on both de novo gene transcription and protein synthesis and results in the activation of transcription from promotors containing the cAMP response element (CRE). Expression of several genes is induced during the establishment of LTP; these include the immediate-early genes (IEGs) BDNF (brain-derived neurotrophic factor), zif268 and C/EBPbeta (CCAAT-enhancer binding protein beta), all of which contain CRE sites within their promotor regions. However, these genes induced by LTP are not known to be rapidly induced following learning in a natural setting. Here we demonstrate rapid and selective induction of BDNF expression during hippocampus-dependent contextual learning.

Amygdala↗
PubMed2000

Evaluation of endothelium-dependent vasodilation in the human peripheral circulation.

Flow-mediated vasodilation (FMD) in the brachial artery measured by ultrasound, and the increase in forearm blood flow (FBF) induced by local infusion of a muscarinic-receptor agonist have both frequently been used to evaluate endothelium-dependent vasodilation (EDV) in the human forearm. The present study intended to evaluate the relationship between these techniques and to investigate if vasodilation induced by the muscarinic receptor-agonist methacholine (MCh) was owing to production of nitric oxide (NO). FMD during hyperaemia was assessed by ultrasound and FBF was measured by venous occlusion plethysmography during local infusion of MCh or L-arginine in the human forearm. Both these methods were applied in 26 individuals. In another 12 individuals forearm arterial and venous plasma concentrations of nitrate/nitrite (NOx) were measured together with FBF before and during local MCh infusion. While the change in brachial artery diameter induced by sublingually given nitroglycerine and the vasodilatory response to sodium nitroprusside (SNP) given locally in the forearm were significantly correlated (r = 0.70, P < 0.01), FMD showed no relationship with the vasodilation evoked by MCh (r = -0.03) or L-arginine (r = 0.04). The five-fold increase in FBF during MCh infusion was associated with a significant increase in venous plasma NOx concentrations (P < 0.05) and a more than 11-fold increase in forearm NOx-release (P < 0.01). Thus, a significant relationship between the two methods regarding the evaluation of endothelium-independent vasodilation evoked by NO-donors was found, but no relationship was found between the two methods regarding the evaluation of endothelium-dependent vasodilation. Furthermore, vasodilation induced by MCh in the forearm seems to be induced by NO-release.

Adult↗
PubMed2000

mu-conotoxin GIIIA interactions with the voltage-gated Na(+) channel predict a clockwise arrangement of the domains.

Voltage-gated Na(+) channels underlie the electrical activity of most excitable cells, and these channels are the targets of many antiarrhythmic, anticonvulsant, and local anesthetic drugs. The channel pore is formed by a single polypeptide chain, containing four different, but homologous domains that are thought to arrange themselves circumferentially to form the ion permeation pathway. Although several structural models have been proposed, there has been no agreement concerning whether the four domains are arranged in a clockwise or a counterclockwise pattern around the pore, which is a fundamental question about the tertiary structure of the channel. We have probed the local architecture of the rat adult skeletal muscle Na(+) channel (mu1) outer vestibule and selectivity filter using mu-conotoxin GIIIA (mu-CTX), a neurotoxin of known structure that binds in this region. Interactions between the pore-forming loops from three different domains and four toxin residues were distinguished by mutant cycle analysis. Three of these residues, Gln-14, Hydroxyproline-17 (Hyp-17), and Lys-16 are arranged approximately at right angles to each other in a plane above the critical Arg-13 that binds directly in the ion permeation pathway. Interaction points were identified between Hyp-17 and channel residue Met-1240 of domain III and between Lys-16 and Glu-403 of domain I and Asp-1532 of domain IV. These interactions were estimated to contribute -1.0+/-0.1, -0.9+/-0.3, and -1.4+/-0.1 kcal/mol of coupling energy to the native toxin-channel complex, respectively. mu-CTX residues Gln-14 and Arg-1, both on the same side of the toxin molecule, interacted with Thr-759 of domain II. Three analytical approaches to the pattern of interactions predict that the channel domains most probably are arranged in a clockwise configuration around the pore as viewed from the extracellular surface.

Amino Acids↗
PubMed2000

Use of a hinged external fixator for elbow instability after severe distal humeral fracture.

The authors report the case of a forty-year-old man who developed acute elbow instability after fixation of an open, comminuted distal humeral fracture. Treatment with a hinged, external elbow fixator was successful in reestablishing elbow stability and a functional range of elbow motion. To the best of the authors' knowledge, the use of this device for acute elbow instability after distal humeral fracture fixation has not been previously reported.

Acute Disease↗
PubMed2000

Antibody reactivity against human and guinea pig tissue transglutaminase in children with celiac disease.

BACKGROUND: Highly discriminatory markers for celiac disease are needed to identify children with early mucosal lesions. The purposes of this study were to evaluate the clinical potential of circulating anti-tissue transglutaminase (tTG) immunoglobulin (Ig)A antibodies in the diagnosis of childhood celiac disease and to investigate the extent of autoreactivity of these antibodies. METHODS: Included in this retrospective study were samples from 22 children with biopsy-verified celiac disease, 23 control subjects with disease, and 22 healthy control subjects without any known gastrointestinal or inflammatory disorders. An enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of IgA antibodies specific for human and guinea pig tTGs. All samples were also analyzed for antibodies to gliadin and endomysium (EMA). RESULTS: The concentrations of IgA specific for human and guinea pig tTGs correlated with the small intestinal villous structure and the serum levels of IgA EMA. The tTG ELISAs exhibited a high specificity and sensitivity for detection of untreated celiac disease. The human erythrocyte IgA tTG ELISA had the highest sensitivity (100%) and a specificity of 98%. The IgA EMA method had a sensitivity of 95% and the highest specificity (100%) of all tests. CONCLUSIONS: Our results provide additional support to the concept that anti-tTG IgA antibodies can be used as a highly discriminatory serologic marker for celiac disease and that measurements of these autoreactive antibodies may in the future be used as an alternative to the EMA test.

Adolescent↗
PubMed2000

Genomic organization of the UGT2b gene cluster on human chromosome 4q13.

The UDP-glucuronosyltransferases (UGTs) comprise a large family of proteins capable of detoxifying a wide variety of both endogenous and exogenous substrates. The primary function of this gene superfamily is to catalyze the glycosylation of substrates such as biogenic amines, steroids, bile acids, phenolic compounds and various other pharmacologically relevant compounds, including numerous carcinogens, toxic environmental pollutants and prescription drugs. This conjugation increases the solubility of these compounds, allowing them to be excreted more readily through hepatic or renal mechanisms. This paper describes the genomic characterization and chromosomal localization of three UGT2B genes which together comprise part of a large cluster of related sequences, including pseudogenes found on human chromosome 4q13. A genomic map spanning approximately 500-1000 kb of this region reveals the presence of three previously described UGT2B genes, at least two previously uncharacterized pseudogenes and a significant number of remnant gene fragments and places UGT2B4 between UGT2B7 and UGT2B15. Additionally, access to a large reference DNA bank allowed us to calculate allele frequencies for two UGT2B SNPs: D85R in UGT2B15 and Q458D in UGT2B4 amongst 803 unrelated individuals representing five ethnic populations. The data presented here suggest a recent evolutionary history of gene duplication, mutation and rearrangement. Furthermore, they suggest that a re-evaluation of the current description of the UGT2B gene family with respect to the number of specific genes, degree of allelic diversity and molecular evolution may be necessary.

Biological Evolution↗
PubMed2000

Characterization of two highly polymorphic human tryptase loci and comparison with a newly discovered monkey tryptase ortholog.

Tryptases are serine proteases involved in mast cell-mediated inflammatory responses which represent potential targets of drugs against diseases such as asthma, arthritis and inflammatory bowel disease. In order to interpret pharmacodynamic data on the tryptase inhibitors undergoing clinical trials, we defined the genetic variability of the tryptase 1 (TPS1) and tryptase 2 (TPS2) loci by screening a reference population of 32 individuals representing three major ethnic groups (Caucasian, African American, Asian). Using overlapping PCR products, we resequenced the entire tryptase genes with the only exclusion of TPS2 intron 1 and 20 bp of TPS2 5' untranslated region included in exon 1 and we identified 21 novel single nucleotide polymorphisms in TPS1 and 17 single nucleotide polymorphisms plus a large polymorphic deletion in the TPS2 gene. We also compared the type, frequency and distribution of single nucleotide polymorphisms in TPS1 and TPS2 and we observed that the polymorphism frequency within these two loci is unexpectedly high (approximately 1 SNP every 90 bp) and that some of the allele frequencies differ significantly among the three ethnic groups. Based on differences observed in preclinical studies using a cynomolgus monkey (Macaca fascicularis) asthma model system, we investigated the difference between monkey and human tryptase genes in order to better understand the mechanism of action of our tryptase inhibitors.

Amino Acid Sequence↗
PubMed2000

Cost effectiveness analysis of school based Mantoux screening for TB infection.

OBJECTIVE: To assess the cost-effectiveness of adding school based Mantoux screening programs to the New South Wales current TB prevention strategy. METHOD: A decision analysis model compared the costs and consequences of screening strategies against the current no-screen strategy. Costs associated with screening and with treating future cases of TB were considered. Consequences considered were deaths and adult cases of TB prevented. The study was based on data from prevalence surveys conducted in 1992 and 1994 in Central and South Western Sydney, New South Wales. Screening strategies considered were screening all or only overseas born (OSB) 6 year olds and all or only OSB 14 year olds in school settings. RESULTS: Screening 14 year olds prevented more deaths and adult cases of TB than screening 6 year olds for a similar cost. For both age groups targeted screening of OSB children was more cost-effective than screening all children. Targeted screening of 14 year olds--the most cost effective option--cost $17,956 (costs and benefits discounted at 5%) per adult case prevented, equivalent to approximately $130,000 per life year saved. The cost-effectiveness ratios decline substantially if lower discount rates and less conservative assumptions are applied. CONCLUSION: Targeted screening was more cost effective than screening all children, however, there are ethical implications of targeting a group based on their origin of birth. IMPLICATIONS: As prevention and control of TB continues to be a high priority for NSW, the implications of a school based screening program should be seriously considered.

Adolescent↗