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Biomedical subjects

J Williams

Publications and source records attributed to J Williams.

At least 361 records · Page 20Linked to original sources

Effects of maturation, artery size, and chronic hypoxia on 5-HT receptor type in ovine cranial arteries.

To test the hypothesis that variations in cerebrovascular reactivity to 5-HT among arteries of different size or type, during maturation, or during acclimatization to high altitude involve differences in serotonergic receptor subtype, we determined relative agonist potency orders and antagonist affinities in common carotid (Com), main branch middle cerebral (Main), and second branch middle cerebral (2BR) arteries from term fetal lambs and nonpregnant adult sheep acclimatized at sea level or at an altitude of 3,820 m for approximately 110 days. In normoxic adult Com segments, agonist potency order was 5-hydroxytryptamine (5-HT) > 5-carboxamidotryptamine (5-CT) >/= 8-hydroxy-2(di-n-propylamino)tetraline (8-OH-DPAT); sumatriptan (Suma) produced no contractile response; and antagonist dissociation constant (pKb) values were 9.4 and 9.5 for ketanserin against 5-HT and 5-CT, 7.5 for GR-127935 against 5-HT, and 7.2 for SB-206553 against 5-HT. In normoxic adult Main segments, agonist potency order was 5-HT > 5-CT >/= Suma >/= DPAT, and pKb values were 9.1 and 9.2 for ketanserin against 5-HT and 5-CT and 7.4 and 8.5 for GR-127935 against 5-HT and Suma, respectively. In the 2BR segments from normoxic adults, agonist potency order was 5-CT > 5-HT > Suma > DPAT and pKb values were 7.4 and 7.2 for ketanserin against 5-HT and 5-CT and 10.0 and 8.7 for GR-127935 against 5-HT and Suma, respectively. Compared with normoxic adults, none of these values were significantly different in hypoxic adults and in fetuses only the pKb values for ketanserin against 5-HT in the 2BR segments (8.8) were greater. From these results we propose that the ratio of 5-HT2 to 5-HT1 receptors is greatest in the Com and decreases progressively to its smallest values in 2BR or smaller segments. Because this gradient appears stable and relatively resistant to the effects of maturation and chronic hypoxia, changes in reactivity associated with these perturbations may involve alterations in receptor density and/or coupling efficiency for 5-HT in ovine cranial arteries.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Single-neuron modeling of LSO unit responses.

We investigated, using a computational model, the biophysical correlates of measured discharge patterns of lateral superior olive (LSO) neuron responses to monaural and binaural stimuli. The model's geometry was based on morphological data, and static electric properties of the model agree with available intracellular responses to hyperpolarizing current pulses. Inhibitory synapses were located on the soma and excitatory ones on the dendrites, which were modeled as passive cables. The active properties of the model were adjusted to agree with statistical measures derived from extracellular recordings. Calcium-dependent potassium channels supplemented the usual Hodgkin-Huxley characterization for the soma to produce observed serial interspike interval dependence characteristics. Intracellular calcium concentration is controlled by voltage- and calcium-dependent potassium channels and by calcium diffusion and homeostatic mechanisms. By adjusting the density of the calcium-dependent potassium channels, we could span the observed range of transient response patterns found in different LSO neurons. Inputs from the two ears were modeled as Poisson processes to describe the responses to tone-burst stimuli. Transient and sustained responses to monaural and binaural tone-burst stimuli over a wide range of stimulus conditions could be well described by varying only the model's inputs. As found in recordings, model responses having similar discharge rates but different binaural stimulus combinations exhibited differences in interval statistics.

Acoustic Stimulation↗

Variations in the management of singleton breech presentation throughout Scotland.

Breech presentation occurs in 3-5% of deliveries and can be managed by either a trial of vaginal breech delivery (TOVBD), external cephalic version (ECV) or Caesarean section. A postal questionnaire was completed by 82% of Scottish consultant obstetricians and revealed wide variations in practice. Eighteen percent never offered ECV. Among those who did consensus was lacking on some contraindications. One-quarter sometimes performed ECV before 37 weeks gestations despite the possibility of spontaneous version. Only 70% restricted ECV to one or more designated operators thereby maintaining levels of expertise. Variations were demonstrated in the use of tocolytics, and pre and post procedure investigations. Following failed ECV 28% considered a repeat attempt and 56% a TOVBD. TOVBD was not offered as first line management by one-fifth of respondents. Those who did varied in the pre-procedure investigations performed. Guidelines are required to ensure safe, consistent practice and avoid unnecessary Caesarean sections.

Breech Presentation↗

Evaluation of a school re-entry nursing intervention for children with cancer.

A retrospective qualitative design was used to identify and compare the concerns, parents, teachers, and children have regarding school re-entry after a cancer diagnosis and to describe the impact of a school re-entry program on parents', teachers', and children's concerns. Audiotaped, semistructured interviews were obtained from a convenience sample of 10 children with cancer (ages 5 to 13 years), 10 mothers, and nine teachers. All participants were positive about the school re-entry nursing intervention, which is described. Results of content analyses indicate that before the intervention, mothers were concerned about their child's safety and peer teasing; teachers were concerned about their own knowledge and peers' adjustment, and children were concerned with keeping up with school activities. After the intervention, mothers were less concerned about peer teasing but continued to be worried about their child's safety in the school setting and began to have concerns about academic progress and physical stamina; teachers reported increased concerns for the child's safety and academic progress, and a desire to return to normal routines in the classroom: and the children continued to have concerns with maintaining academic and/physical progress. Clinical and research implications are discussed.

Adolescent↗

Coping with loss: the development and evaluation of a children's bereavement project.

The 'Kingfisher Project' is a community-based programme of support groups for bereaved children. It has been developed by a multi-disciplinary group of workers from health, education, social services and the voluntary sector. Thirty-six children and young people have have been through the first five groups of the programme. Children accessing the service are predominantly those at high risk of developing longer-term problems as a result of bereavement. Evaluation indicates that the children and young people benefit in terms of increased social, behavioural, emotional and physical well-being. Two sub-groups appear to have benefited less: these are children and young people with learning difficulties, and teenage girls. Project evaluation has enabled workers to develop insights into the programme's strengths and weaknesses and has raised questions which merit further exploration.

Adaptation, Psychological↗

Differential regulation of matrix metalloproteinases and their inhibitors in human glomerular epithelial cells in vitro.

The present study examines the effect of transforming growth factor-beta1 (TGF-beta1) and interleukin-1beta (IL-1beta) on the regulation of gelatinase A, gelatinase B, tissue inhibitor of metalloproteinase-I (TIMP-I) and TIMP-II in human glomerular epithelial cells (GEC). The addition of TGF-beta1 resulted in the increased production and secretion of both gelatinase A (72-kD type IV collagenase) and gelatinase B (92-kD type IV collagenase), in a dose- and time-dependent manner. In contrast, the addition of IL-1beta to GEC resulted in the stimulation of secretion of gelatinase B but not gelatinase A. When the secretion of the regulatory inhibitors was examined, IL-1beta or TGF-beta1 both resulted in an increased secretion of TIMP-I, whereas the secretion of TIMP-II was downregulated. Such results demonstrate an independent and opposite regulation of the enzymes and their inhibitors. Of particular interest was the observation of the differential regulation of gelatinase A and its specific inhibitor TIMP-II (which binds to the latent form of this enzyme) in response to TGF-beta1. These results for the first time indicate that in human GEC, matrix metalloproteinases (MMP), as well as their specific inhibitors, are independently regulated by different cytokines. MMP and their regulatory tissue inhibitors (TIMP) play an important role in tissue remodeling. The results of the present study serve to emphasize both the complex regulation of matrix metabolism in the glomerulus and the potential pathologic role of an imbalance between the proteinases and their inhibitors in various forms of glomerular disease.

Base Sequence↗

Malaria imported into the United Kingdom in 1996.

Virtually all malaria infections seen in the United Kingdom (UK) in recent years have been contracted overseas and imported into the UK, apart from two cases in 1976 due to imported infected mosquitoes and occasional cases of congenital or of transfusion

Journal Article↗

The impact of depression on the physical health of family members.

BACKGROUND: Depressive illness is common. Depression in one family member is associated with an increased incidence of psychopathology in other family members. There are no data on the physical well being of the families of depressed individuals. AIM: To compare physical morbidity of family members of depressed patients with that of family members of comparison patients. METHOD: A comparative follow-up study from case notes. Two hundred and one subjects from 88 families with an index family member diagnosed with depression ('depression families') were compared with 200 subjects from 88 families with a matched index subject without depression ('comparison families'), using the Duke University Illness Severity Scores (ISS) to assess burden of illness experienced by both groups. RESULTS: The cumulative incidence of depression over 11 months in depression families was 8.9% compared to 1.4% in the Family Practice Unit as a whole. Members of depression families had significantly greater ISS than members of comparison families (difference in means = 0.164; 95% confidence interval (CI) 0.113-0.215; P < 0.001). Excluding family members with depression (in addition to the index subject), ISS of members of depression families remained significantly greater than the comparison group (difference in means = 0.136; 95% CI 0.083-0.189; P < 0.001). Among depression families, mean ISS was significantly higher after presentation of depression in index subjects compared with before (difference in means = 0.155; 95% CI 0.115-0.194; P < 0.0001). No significant difference was seen between ISS of depression and comparison families before presentation of depression (difference in means = 0.008; 95% CI -0.004-0.058; P = 0.74). CONCLUSION: Depression in patients is associated with increased physical morbidity in their families.

Adult↗

Cognitive correlates of single neuron activity in task-performing animals: application to ethanol research.

The deleterious effects of ethanol on cognitive processes result from an interaction between ethanol and the neural structures that are critical for executing those cognitive functions. Results from studies that employ contemporary behavioral neuroscience techniques are beginning to elucidate the neural circuits that underlie specific cognitive processes, and the stage is set for rigorous investigations into the neural basis for ethanol-induced cognitive impairments. In this article, the application of single neuron recording techniques to the study of the memory and attentional deficits produced by acute exposure to low levels of ethanol are described, with an emphasis on the advantages of combining physiological techniques with operant behavioral procedures in rats. After reviewing background information on the basic neurophysiological and behavioral techniques, empirical results from this laboratory will be used to illustrate how single-unit analysis can be applied to the study of ethanol-induced cognitive impairments.

Alcoholism↗

Microfilaremia from a Dirofilaria-like parasite in Greece. Case report.

In Europe, zoonotic filarial infections in humans are caused by two species, Dirofilaria immitis and Dirofilaria repens. These parasites are associated mainly with embolic infarcts of the pulmonary artery and subcutaneous nodules, respectively. An unusual dirofilarial infection in a Greek patient who showed marked eosinophilia and microfilaremia is presented. Although the identification of Dirofilaria species is not conclusive, this report is the first on a case of microfilaremia from a Dirofilaria infection in an immunocompetent patient.

Aged↗

Preservation of residual vision 2 years after stereotactic radiosurgery for a presumed optic nerve sheath meningioma.

We performed stereotactic radiosurgery on a patient with a presumed optic nerve sheath meningioma with a progressive optic neuropathy and an intact peripheral visual field. The patient's visual acuity and visual field have remained stable for 2 years following treatment, and the appearance of the tumor has not changed by neuroimaging. We believe that stereotactic radiosurgery is a viable option for treating optic nerve sheath meningioma.

Adult↗

Neurocristic cutaneous hamartoma: a distinctive dermal melanocytosis with an unknown malignant potential.

Neurocristic hamartomas (NCHs) result from aberrant development of the neuromesenchyme. In addition to a dermal melanocytic component, these tumors can contain neurosustentacular and fibrogenic components and can undergo malignant transformation. Although NCHs have many features in common with other dermal melanocytic neoplasms, including cellular blue nevi and some congenital nevi, they have distinctive clinical and histologic features. We present a case report of a 27-year-old white woman with an NCH of the scalp. The clinical, histologic, and immunohistochemical features are compared with those of other dermal melanocytic neoplasms. The NCH contained epithelioid pigmented melanocytes positive for S-100 and HMB45, within which there were well-circumscribed nodules of S-100+/Leu 7+/HMB45- cells surrounded by a capsule composed of spindle cells positive for epithelial membrane antigen. The stromal cells throughout the tumor were diffusely CD34 positive, and hair follicles were decreased and dystrophic within the tumor. NCHs represent neoplastic dysplasia that involves not only melanocytic cells but also neurosustentacular and fibrocytic effector cells. The histologic and immunohistochemical features, along with the decreased and dystrophic hair follicles, suggest that the abnormalities in the mesenchyme are significant and result from the contribution of neural crest cells to the cellular and matrix components of the mesenchyme.

Adult↗

The role of the general practitioner in the community care of people with HIV infection and AIDS: a comparative study of high- and low-prevalence areas in England.

BACKGROUND: Policy for the care of people suffering from HIV and AIDS has changed over the past decade. Schemes for shared primary and secondary care have been met with varying success, and patients may be reluctant to become involved. No systematic evaluation comparing the views of primary care providers and users in areas of varying HIV prevalence has been published. AIM: To examine the role of general practice in areas of England with low and high human immunodeficiency virus (HIV) prevalence and to compare barriers to general practice care in each area. METHOD: We used focus groups, semistructured questionnaires and interviews in north London (high HIV prevalence) and Nottingham (low HIV prevalence). RESULTS: Four focus groups took place in London. A total of 411 general practitioners (GPs) in London and 405 in Nottingham replied to postal questionnaires. Overall, 121 primary care staff in 40 London practices and 26 staff in five Nottingham practices were interviewed. In all, 54 people infected with HIV were interviewed in London and 20 in Nottingham. Providers and users regarded the 24-hour availability and the familiar environment of general practice as its key assets. Lack of expertise and time were its disadvantages. Providers were concerned about inadequate communication with specialist services. Although providers were concerned about confidentiality, whether they had liberal and sympathetic attitudes was more important in deciding whether people with HIV used the service. In the low-prevalence area, general practice involvement was the result of individual initiatives, and practices were not integrated into specialist care. In the high-prevalence area, HIV care was more usual in general practice, but there was also little integration with HIV services. CONCLUSIONS: In high-prevalence districts, a strategy to make HIV care routine for all GPs may be appropriate. In low-prevalence areas, a network of selected, strategically located, relatively high-involvement practices may be more effective in meeting the primary care needs of people with HIV infection and acquired immunodeficiency syndrome (AIDS).

Community Health Services↗

Comparison of PRA-STAT, sHLA-EIA, and anti-human globulin-panel reactive antibody to identify alloreactivity in pretransplantation sera of heart transplant recipients: correlation to rejection and posttransplantation coronary artery disease.

BACKGROUND: Screening pretransplantation recipient sera for percent panel reactive antibodies (%PRA) by an anti-human globulin (AHG) assay may identify recipients who are at risk for graft rejection or development of posttransplantation coronary artery disease. However, the pretransplantation AHG-%PRA does not always correlate with the occurrence of graft rejection or coronary artery disease. METHODS: We compared the predictive capacity of the AHG-%PRA with that of an enzyme-linked immunoassay (EIA)-based PRA assay that identifies immunoglobulin G bound to soluble human leukocyte antigen (sHLA) class I molecules from pooled platelets of 240 random donors (sHLA-EIA), and that of an EIA-based assay that detects immunoglobulin G anti-HLA class I antibodies bound to sHLA derived from individual HLA-typed cell cultures (PRA-STAT). The pretransplantation sera from 130 cardiac allograft recipients were comparatively tested and results evaluated. RESULTS: Although AHG-%PRA- and sHLA-EIA-determined PRA results were comparable, neither assay discriminated potential recipients at risk for rejection or coronary artery disease. However, cardiac allograft recipients with pretransplantation PRA-STAT sera > 10% were at risk for (1) graft rejection (77% vs 56%, p < .05); (2) more rejections/recipient (1.9 vs 1.0, p < .02); (3) graft rejection within 30 days (92% vs 38%, p < .001); or (4) development of coronary artery disease (48% vs 23%, p < .05) than recipients with pretransplantation PRA-STAT sera < 10%. CONCLUSIONS: PRA-STAT analysis of pretransplantation sera from potential cardiac allograft recipients may be more clinically informative about HLA alloimmunity and a better predictor of adverse clinical events than either AHG-%PRA- or sHLA-EIA-determined PRA.

Antibody Specificity↗

Isolation and chondrocytic differentiation of equine bone marrow-derived mesenchymal stem cells.

OBJECTIVE: To isolate mesenchymal stem cells from adult horses and determine specific monolayer culture conditions required to enhance biochemically and phenotypically defined chondrocytic differentiation. ANIMALS: 2 adult horse bone marrow donors without skeletal or hematologic abnormalities. PROCEDURE: Bone marrow was aspirated from the sternebra, and mesenchymal stem cells were isolated by centrifugation and cultured in monolayers. Subcultures were established in 24-well plates on day 13. Culture medium was harvested every 2 days, and culture of 12 of the 24 wells was terminated on day 6 and of the remaining wells on day 12. Medium proteoglycan content was determined for all samples, and proteoglycan monomeric size was determined for pooled samples from days 2-6 and 8-12. Total nucleated cell numbers were determined at culture termination on days 6 and 12. Histologic, histochemical, and collagen immunohistochemical analyses of multiwell chamber slides harvested on day 6 or 12 were performed. RESULTS: Mesenchymal cells were an abundant cellular constituent of bone marrow aspirates, and separation of hematopoietic elements was achieved by centrifugation and delayed medium exchange. The remaining mesenchymal stem cells progressed from large, spindyloid, fibroblastic-appearing cells to a rounder shaped cell which formed colony plaques; isolated cells remained more spindyloid. Mesenchymal cell transformation toward a chondrocytic phenotype was verified by a shift in expression from collagen type I to type II, and an increase in quantity and molecular size of proteoglycans synthesized over time. CONCLUSIONS: Mesenchymal stem cells obtained from adult horses have the capacity to undergo chondrogenic differentiation in monolayer cultures and may provide a locally recruitable or transplantable autogenous cell source for articular cartilage repair.

Animals↗