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Biomedical subjects

C S Smith

Publications and source records attributed to C S Smith.

At least 37 records · Page 2Linked to original sources
PubMed1998

Nitric oxide induces cell death in a catecholaminergic cell line derived from the central nervous system.

The nitric oxide (NO) donors, sodium nitroprusside (SNP), 1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium+ ++-1,2-diolate] (DETA NONOate), and S-nitroso-N-acetyl-D,L-penicillamine (SNAP) produce a dose-dependent increase in cell death in a catecholaminergic cell line (CATH.a) derived from the central nervous system. Cell death is associated with a decrease in mitochondrial membrane potential. Dopamine also induced cell death of CATH.a cells and this was potentiated by concentrations of SNP which alone did not produce cell death. Hemoglobin, a scavenger of NO radicals, blocked SNP- and SNAP-induced cell death. Catalase and superoxide dismutase, enzymes that metabolize H2O2 and superoxide, respectively, did not inhibit SNP- or SNAP-induced cell death. These data indicate that NO donors produce cell death in CATH.a cells through a mechanism related to the production of NO and the loss of the mitochondrial membrane potential but unrelated to the production of H2O2.

Catalase↗
PubMed1998

Analysis of alpha2u-globulin in rat urine and kidneys by liquid chromatography-electrospray ionization mass spectrometry.

A quantitative method was developed for determination of alpha2u-globulin in urine and kidney samples collected from male rats using liquid chromatography-electrospray ionization mass spectrometry (LC-ESI/MS). Samples prepared from urine and kidney homogenates using size exclusion filters were subject to reversed-phase liquid chromatography and the effluent passed into an electrospray ionization source. Quantitative analysis using external standard calibration was based upon selected ion monitoring of protonated molecular ions by the mass spectrometer. Linear calibration curves were developed over the range of approximately 4. 6-370 microg of alpha2u-globulin/microL for spiked urine standards and over the range of approximately 4.6-550 microg of alpha2u-globulin/microL for spiked kidney standards. The precision (relative standard deviation) for repeated injection (using urine samples) and intra-assay precision (using both urine and kidney samples) were within +/-10.4% and +/-13.2%, respectively. Using spiked urine standards, inter-assay precision, intra-assay accuracy, and inter-assay accuracy were within +/-20%, +/-20%, and +/-15%, respectively. Using spiked kidney standards, intra-assay accuracy was within +/-15%. The limits of detection (LOD) for the determination of alpha2u-globulin in urine and kidney samples were approximately 0.41 pg/nL (1.0 fmol injected) and 25 pg/nL ( approximately 13 fmol injected), respectively. The limits of quantitation (LOQ) for determination of alpha2u-globulin in urine and kidney samples were calculated as 1.4 pg/nL (3.7 fmol injected) and 83 pg/nL (45 fmol injected), respectively. Applicability of the LC-ESI/MS method was demonstrated by determination of alpha2u-globulin in both urine and kidney samples collected from male Fischer 344/N rats dosed intravenously with cis-Decalin at concentrations of 0, 2.5, 5.0, 10, and 20 mg/kg. A dose-dependent relationship was found between the amount of cis-Decalin administered and alpha2u-globulin accumulation in kidney samples, whereas no significant change in the urinary levels of alpha2u-globulin occurred. These observations are consistent with excessive accumulation of alpha2u-globulin occurring in protein droplets in renal proximal tubule epithelial cells as a result of decreased catabolic activity due to formation of ligand-protein complexs with Decalin and its metabolite(s). This report demonstrates that LC-ESI/MS may be routinely applied for quantitative analysis of alpha2u-globulin in rat urine and kidney samples to address alpha2u-globulin accumulation and its role in the development of nephrotoxicity associated with chemical exposures.

Alpha-Globulins↗
PubMed1998

A common and recurrent 13-bp deletion in the autoimmune regulator gene in British kindreds with autoimmune polyendocrinopathy type 1.

Autoimmune polyendocrinopathy type 1 (APS1) is an autosomal recessive disorder characterized by autoimmune hypoparathyroidism, autoimmune adrenocortical failure, and mucocutaneous candidiasis. Recently, an autoimmune regulator gene (AIRE-1), which is located on chromosome 21q22.3, has been identified, and mutations in European kindreds with APS1 have been described. We used SSCP analysis and direct DNA sequencing to screen the entire 1,635-bp coding region of AIRE-1 in 12 British families with APS1. A 13-bp deletion (964del13) was found to account for 17 of the 24 possible mutant AIRE-1 alleles, in our kindreds. This mutation was found to occur de novo in one affected subject. A common haplotype spanning the AIRE-1 locus was found in chromosomes that carried the 964del13 mutation, suggesting a founder effect in our population. One of 576 normal subjects was also a heterozygous carrier of the 964del13 mutation. Six other point mutations were found in AIRE-1, including two 1-bp deletions, three missense mutations (R15L, L28P, and Y90C), and a nonsense mutation (R257*). The high frequency of the 964del13 allele and the clustering of the other AIRE-1 mutations may allow rapid molecular screening for APS1 in British kindreds. Furthermore, the prevalence of the 964del13 AIRE-1 mutation may have implications in the pathogenesis of the more common autoimmune endocrinopathies in our population.

Alleles↗
PubMed1998

Causes and characteristics of the street child phenomenon: a global perspective.

The street child phenomenon is an alarming and escalating worldwide problem. Street children are maltreated, imprisoned and, in some countries, killed. Street children, as the offspring of complex contemporary urban environments, represent one of our most serious global challenges. This article investigates the causes of this phenomenon, as well as the characteristics of street children throughout the world. In addition, the specific circumstances of street children in Nepal, Indonesia, India, Latin America, and the Philippines are discussed.

Child↗
PubMed1998

Psychological characteristics of South African street children.

Millions of children worldwide are subjected to poverty, abuse, and neglect, yet only a minority choose to abandon their homes in search of a supposedly better life on the street. This article seeks to identify the psychological characteristics that predispose certain children to run away and to survive, often for long periods, on the streets of South Africa. Vulnerability and resilience are examined, as well as social conditions that mediate the psychological predisposition to become a street child.

Adolescent↗
PubMed1998

Public perceptions of, and reactions to, street children.

Research has shown that no treatment program designed for street children can succeed unless the community is prepared to respect, protect, and provide opportunities for them (Tacon, cited in Schurink & Rip, 1993). Unfortunately, these children are abused in many parts of the world (Aptekar, 1994). This paper investigates why the general public, as well as those charged with enforcing the law, often treat street children with scorn and hostility.

Adolescent↗
PubMed1998

Is the street child phenomenon synonymous with deviant behavior?

The police, court officials, social workers, and the public, in general, perceive street children negatively--their behavior is deemed deviant. This paper examines the concept of deviance as a label placed on the powerless by those in positions of power.

Adolescent↗
PubMed1997

Normal MR appearances of the posterior pituitary in central diabetes insipidus associated with septo-optic dysplasia.

Magnetic resonance (MR) imaging of the pituitary in children with central diabetes insipidus usually shows absence of the normal high signal within the posterior gland. The high signal of the normal posterior pituitary is thought to be due to the presence of intra- cellular storage granules of vasopressin. MR imaging has been advocated as a useful investigation to aid in the distinction between central diabetes insipidus and other causes of thirst and polydipsia. We report the case of an infant with central diabetes insipidus in association with septo-optic dysplasia in whom MR imaging showed normal appearances of the posterior pituitary. The mechanism of central diabetes insipidus in this case may be related to a failure of hypothalamic function affecting osmoreception, rather than to a deficiency of vasopressin. Normal MR appearances of the pituitary do not exclude central diabetes insipidus in infants with midline cerebral malformations.

Abnormalities, Multiple↗
PubMed1997

Bone mineral density in Turner's syndrome--a longitudinal study.

OBJECTIVE: Osteoporosis is a recognized problem in adult women with Turner's syndrome, the aetiology of which is unclear. The aim of this study was to examine bone mineralization longitudinally in a group of girls with Turner's syndrome and to study the effect of different treatments on bone mineral density. DESIGN: A prospective observational study. PATIENTS: Eighteen girls with Turner's syndrome aged 4-17 years attending a paediatric endocrine clinic. MEASUREMENTS: Bone mineral density of the lumbar spine was assessed using dual energy X-ray absorptiometry at several time points over a 2.5-year period. RESULTS: Only one girl had evidence of a significant reduction in bone density when comparisons were made with control data related to body weight and pubertal status. No advantage was found for any form of treatment in optimizing bone mineralization. CONCLUSIONS: As there is little evidence of reduced bone mineral density in girls with Turner's syndrome there is no justification for an early introduction of oestrogen replacement during the prepubertal years.

Adolescent↗
PubMed1997

The roles of experience and reflection in ambulatory care education.

While ambulatory care education typically does not provide much direct instruction, supervision, or feedback, experiential learning occurs. Using experiential learning theory, the authors describe how this process of learning works. the process is characterized by a cycle of having a concrete experience (e.g., an encounter with a patient), reflecting on that experience as it unfolds, formulating conceptualizations and generalizations from the experience, and testing those generalizations and concepts in other situations. With this model in mind, the authors make four recommendations for improving ambulatory care education for both medical students and residents: (1) plan for experiences in carefully selected ambulatory care settings; (2) facilitate reflective observation; (3) encourage conceptual thinking and inquiry; and (4) promote feedback and testing of insights from experiences. The authors discuss the rationale behind each recommendation and offer guidelines for how each might be implemented.

Ambulatory Care↗
PubMed1996

Strong hydrogen bonding interactions involving a buried glutamic acid in the transmembrane sequence of the neu/erbB-2 receptor.

The receptor tyrosine kinase encoded by the neu/erbB-2 proto-oncogene is constitutively activated by a single valine to glutamic acid substitution at position 664 in the predicted membrane-spanning sequence of the receptor. We have explored the structural changes involved in receptor activation with polarized FTIR and magic angle spinning NMR spectroscopy. The hydrophobic transmembrane sequence folds into a well-defined alpha-helical structure spanning the membrane bilayer. Measurements of the pKa and 13C chemical shift anisotropy of Glu 664 reveal that the side chain carboxyl group is protonated and strongly hydrogen bonded. These studies provide direct evidence for glutamate hydrogen-bonding interactions in the mechanism of receptor dimerization and activation.

Amino Acid Sequence↗
PubMed1996

A theoretical model for nursing systems outcomes research.

Nursing research on patient and administrative outcomes has typically examined the relationships between selected structural characteristics and outcomes, without taking into account the organization's context. In contrast, health services research has focused on the relationships between the organization's context and outcomes, most often mortality, without taking into account structural characteristics. Although widely used, both approaches develop fragmented knowledge. This article describes a comprehensive theoretical model that takes into account the relationships among the organization's context, its structure, and both patient and nursing administrative outcomes.

Humans↗
PubMed1996

Genetic homogeneity of autoimmune polyglandular disease type I.

Autoimmune polyglandular disease type I (APECED) is an autosomal recessive autoimmune disease (MIM 240300) characterized by hypoparathyroidism, primary adrenocortical failure, and chronic mucocutaneous candidiasis. The disease is highly prevalent in two isolated populations, the Finnish population and the Iranian Jewish one. Sporadic cases have been identified in many other countries, including almost all European countries. The APECED locus has previously been assigned to chromosome 21q22.3 by linkage analyses in 14 Finnish families. Locus heterogeneity is a highly relevant question in this disease affecting multiple tissues and with great phenotypic diversity. To solve this matter, we performed linkage and haplotype analyses on APECED families rising from different populations. Six microsatellite markers on the critical chromosomal region of 2.6 cM on 21q22.3 were analyzed. Pairwise linkage analyses revealed significant LOD scores for all these markers, maximum LOD score being 10.23. The obtained haplotype data and the geographic distribution of the great-grandparents of the Finnish APECED patients suggest the presence of one major, relatively old mutation responsible for approximately 90% of the Finnish cases. Similar evidence for one founder mutation was also found in analyses of Iranian Jewish APECED haplotypes. These haplotypes, however, differed totally from the Finnish ones. The linkage analyses in 21 non-Finnish APECED families originating from several European countries provided independent evidence for linkage to the same chromosomal region on 21q22.3 and revealed no evidence for locus heterogeneity. The haplotype analyses of APECED chromosomes suggest that in different populations APECED is due to a spectrum of mutations in a still unknown gene on chromosome 21.

Alleles↗
PubMed1995

Four-contrast defecography: pelvic "floor-oscopy".

PURPOSE: This study was designed to determine the accuracy of physical examination (as judged by four-contrast defecography) for women with pelvic floor relaxation disorders. METHODS: Sixty-two women (mean age, 59 years) who had obstructed defecation or constipation, vaginal prolapse, urinary difficulty, or pelvic pain underwent four-contrast defecography. Oral, vaginal, bladder, and rectal contrast were administered selectively and fluoroscopy was performed. Radiographic findings were compared with physical examination diagnosis. RESULTS: Four-contrast defecography changed the diagnosis in 46 patients (75 percent); 26 percent of presumed cystoceles, 36 percent of enteroceles, and 25 percent of rectoceles were not present on defecography. Defecography also revealed unsuspected coexisting defects in addition to known abnormalities detected on physical examination. In contrast, when physical examination was negative for these defects, 63 percent of patients were found to have cystoceles, 46 percent to have enteroceles, and 73 percent to have rectoceles on four-contrast defecography. The discovery of Grade 2 or 3 unsuspected abnormalities was significant, especially so for enteroceles. For posterior vaginal eversions extending to or past the introitus, physical examination was accurate in only 61 percent. Physical examination of large anterior defects was more accurate, with 74 percent of patients being correctly diagnosed. CONCLUSIONS: Physical examination diagnosis of pelvic floor relaxation disorders is frequently inaccurate, especially for large vaginal eversions. Four-contrast defecography improves diagnostic accuracy, helps to identify all pelvic floor defects before surgery, and can assist with planning the correct operative approach.

Defecation↗
PubMed1995

Health services management education in South Australia.

In December 1994 the Australian College of Health Service Executives (SA Branch) sought 'a needs analysis for health management training programs within South Australia'. Although the college was interested in a range of matters, the central issue was whether the current Graduate Diploma in Health Administration (or a similar course) would continue to be provided in Adelaide. The college provided background material and discussions were held with students, the health industry, relevant professional associations and the universities. This commentary sets out some of the background factors and my conclusions, which have been accepted by the South Australian authorities.

Curriculum↗
PubMed1995

The impact of an ambulatory firm system on quality and continuity of care.

The author assessed the effects on quality and continuity of care at a Veterans Affairs hospital as a result of its conversion to an interdisciplinary firm system. Before the firm system was implemented, ambulatory care at the hospital was provided in two medicine clinic areas and in one unscheduled "walk-in" clinic. Care for intercurrent illnesses was frequently not coordinated. The staff from eight clinical services were involved in restructuring into three, interdisciplinary firm teams. These firm teams were created without the addition of new staff. Quality was defined by patient satisfaction, staff satisfaction, re-admissions within 10 days of a hospital discharge, and length of visit. Continuity was defined by percentage of visits to the primary care team (defined as the physician or the physician paired with midlevel practitioner if applicable). Patient satisfaction increased from 4.43 to 4.84 (5-point Likert scale, P < .001). Staff satisfaction increased from 4.3 to 6.24 (7-point Likert scale, P < .001). Re-admissions within 10 days of hospital discharge decreased by 28% (P < .01). Length of visit decreased by 9.5% (P < .0001). Continuity improved from 47% to 69% of visits to the primary care team (P < .002). These results more than justified the staff time needed to convert to a firm system.

Ambulatory Care↗
PubMed1995

Urinary pyridinoline and deoxypyridinoline excretion in children.

OBJECTIVE: There are few data on urinary markers of collagen breakdown in children. We have determined a normal range for urinary pyridinoline and deoxypyridinoline in children, assessed the variability in excretion in individual children and examined the effect of GH treatment on the excretion of these collagen cross-links. DESIGN: A cross-sectional study of a group of healthy children and sequential samples from children receiving GH treatment. PATIENTS: One hundred and nine healthy children aged 2-15 years, 8 healthy children aged 4-11 years and 4 children receiving GH treatment. MEASUREMENTS: Total pyridinoline and deoxypyridinoline excretion were measured by high performance liquid chromatography after initial acid hydrolysis and cellulose extraction steps. Serum parathyroid hormone was measured using a two-site immunoradiometric assay and urinary hydroxyproline by Ehrlich's reaction using a colorimetric assay. Pyridinoline and deoxypyridinoline excretion were expressed as a ratio against urine creatinine. RESULTS: High excretion of pyridinoline (Pyr) and deoxypyridinoline (DPyr) was seen at all ages with no apparent relation to age (mean Pyr/Cr 115 nmol/mmol and DPyr/Cr 31 nmol/mmol). No correlation was found with serum parathyroid hormone or urinary hydroxyproline excretion. Marked day to day variation was seen in individual children. A progressive rise in excretion was seen in children receiving GH treatment with no significant correlation to height velocity. CONCLUSIONS: There is a high excretion of the pyridinium cross-linking amino acids in children of all ages compared to adults. However, a high variability exists in single morning urine samples which will limit the usefulness of these markers in growing children.

Adolescent↗