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Biomedical subjects

J A Smith

Publications and source records attributed to J A Smith.

At least 109 records · Page 6Linked to original sources
PubMed2000

Longitudinal growth in infants and young children treated with budesonide inhalation suspension for persistent asthma.

BACKGROUND: Results of recent growth studies suggest that inhaled glucocorticosteroids may affect growth in children. OBJECTIVE: Three 52-week, open-label extension studies (studies A, B, and C) were conducted to compare the effects of budesonide inhalation suspension (BIS) with conventional asthma therapy (CAT) on long-term safety, including intermediate-term growth, in 3 different pediatric asthma populations. METHODS: Pediatric asthma patients (ages 6 months to 8 years) from 3 multicenter, randomized, 12-week, double-blind, placebo-controlled studies were eligible to enroll in the 52-week, open-label extension studies. The extension studies were multicenter, randomized, open-label, active-controlled, parallel-group studies performed at 26 centers in the United States. Subjects in each extension study were randomized in a 2:1 ratio to receive either BIS or CAT. BIS was initially administered at a dose of 0.5 mg once (studies A and C) or twice daily (study B), with attempts made at each clinical visit to gradually reduce the dose to the minimum effective dose that maintains asthma control, as judged by the investigator. CAT consisted of any available therapy for asthma, including inhaled glucocorticosteroids in studies B and C only. Height SD scores, growth velocity, and skeletal age (only in studies B and C) were examined. RESULTS: In total, 670 subjects were randomized; 223 subjects received CAT and 447 received BIS. Mean ages at entry were 63.0 months and 60.9 months in CAT and BIS groups, respectively. Median total daily doses of BIS ranged from 0.5 to 1. 0 mg and the mean duration of treatment exposure was 304 +/- 119 days and 342 +/- 83 days in CAT and BIS groups, respectively. Changes in height SD scores differed significantly between the BIS and CAT groups in study A (-0.19, P =.003), and there was a small, statistically significant decrease in growth velocity (-0.8 cm/y, P =.002) in the BIS-treated group compared with the CAT group. No significant differences were observed between BIS and CAT groups in the changes in height SD scores or in growth velocities in studies B (+0.10 and +0.7 cm/y, respectively) and C (+0.12 and +0.8 cm/y, respectively). No differences in skeletal age were observed between BIS and CAT groups in studies B and C. CONCLUSION: There was a small, statistically significant decrease in growth velocity in the BIS-treated group compared with the CAT group in the study (study A) where inhaled glucocorticosteroid use was prohibited before entry and in the CAT group during the study. In the studies (B and C) where inhaled glucocorticosteroids were allowed in the CAT group, no differences were observed in height SD scores or growth velocity. The clinical relevance of these effects, including impact on final adult height, remain to be determined in prospectively planned studies that assess growth in children.

Administration, Inhalation↗
PubMed2000

Surgical management of noninvasive bladder cancer (stages Ta/T1/CIS).

Transurethral removal of bladder cancer is performed for diagnostic and therapeutic reasons. Tissue is returned for histologic determination of tumor grade and stage. For tumors that do not invade the detrusor muscle, resection can be curative although there is a high rate of new tumor occurrence. Surgical removal not only eradicates visible existing lesions but also retrieves material for histologic evaluation. This examination allows a determination of tumor grade as well as stage. Because of the importance of good histologic information in determining prognosis and, possibly, the need for further therapy, the method of surgical removal is important.

Biopsy↗
PubMed2000

A Src SH2 selective binding compound inhibits osteoclast-mediated resorption.

BACKGROUND: The observations that Src(-/-) mice develop osteopetrosis and Src family tyrosine kinase inhibitors decrease osteoclast-mediated resorption of bone have implicated Src in the regulation of osteoclast-resorptive activity. We have designed and synthesized a compound, AP22161, that binds selectively to the Src SH2 domain and demonstrated that it inhibits Src-dependent cellular activity and inhibits osteoclast-mediated resorption. RESULTS: AP22161 was designed to bind selectively to the Src SH2 domain by targeting a cysteine residue within the highly conserved phosphotyrosine-binding pocket. AP22161 was tested in vitro for binding to SH2 domains and was found to bind selectively and with high affinity to the Src SH2 domain. AP22161 was further tested in mechanism-based cellular assays and found to block Src SH2 binding to peptide ligands, inhibit Src-dependent cellular activity and diminish osteoclast resorptive activity. CONCLUSIONS: These results indicate that a compound that selectively inhibits Src SH2 binding can be used to inhibit osteoclast resorption. Furthermore, AP22161 has the potential to be further developed for treating osteoporosis.

Amino Acid Sequence↗
PubMed2000

Neutrophil oxidative activity is differentially affected by exercise intensity and type.

The differential effects of exercise intensity and type on neutrophil activation were assessed in eight well-trained male runners. Each subject undertook, on different days, three separate 40 min interval (8 x 5 min) treadmill bouts: an intense uphill run (90% VO2 max), a moderate-intensity near-level run and an eccentrically-biased downhill run (both at 52% VO2 max). Blood granulocyte count increased (p< 0.05) after all three treadmill bouts (range 25-108%). Chemiluminescence activity of isolated neutrophils decreased (p< 0.05) immediately after (-58%) and 1-h after (-72%) uphill running, but became significantly elevated (p< 0.05) at 6-h after the near-level (+71%) and downhill (+84%) runs. The ability of neutrophils to release the superoxide anion radical was reduced (p< 0.05) immediately after near-level (-29%) and uphill (-21%) running in cells stimulated with opsonized zymosan. Epinephrine concentration increased by 430% (p=0.01) after uphill but not with near-level or downhill running. The plasma concentration of elastase increased (p< 0.05) immediately after uphill and near-level running, and one hour after uphill running. These results suggest that a population of neutrophils mobilised into the circulation became directly activated in response to exercise, and that neutrophil oxidative activity is affected differentially by both the intensity and type of exercise undertaken.

Adult↗
PubMed2000

Intestinal trehalase activity in a UK population: establishing a normal range and the effect of disease.

Trehalose is a disaccharide, the main dietary source being mushrooms. It has been approved as an additive in the preparation of dried food. Isolated intestinal trehalase deficiency is found in 8% of Greenlanders, but is rare elsewhere. The normal range of trehalase activity and the incidence of isolated trehalase deficiency in the UK have not been reported. Patients (n 400) were investigated for suspected malabsorption. Endoscopic distal duodenal biopsies were taken for histological assessment and maltase, sucrase, lactase and trehalase estimation. Disaccharidase activities were determined by Dahlqvist's technique (Dahlqvist, 1968). Most patients (n 369) had normal duodenal histology. In these, square root transformation of trehalase activity produced a normal distribution. The normal range (mean +/- 2 SD) was 4.79-37.12 U/g protein. One patient had an isolated borderline trehalase deficiency. The thirty-one patients with villous atrophy had significantly reduced disaccharidase activities. With ingestion of a gluten-free diet, maltase, sucrase and trehalase activities recovered to normal in most patients, whereas lactase activity did not. The normal range and very low incidence of isolated enzyme deficiency is comparable with that described in populations from the USA and mainland Europe. Activity is significantly reduced in untreated coeliac disease and recovers with treatment with a gluten-free diet. There is no place for routine determination of trehalase activity in the UK population and there should be no concern over the introduction of trehalose-containing dried foods.

Adolescent↗
PubMed2000

Genetic variation in the bovine myostatin gene in UK beef cattle: allele frequencies and haplotype analysis in the South Devon.

Work on Belgian Blue cattle revealed that an 11 base pair (bp) deletion within the bovine myostatin gene (GDF8) is associated with the double-muscled phenotype seen in this breed. Investigations focusing on other European breeds known to show double-muscling identified several mutations within the coding region of the gene associated with the double-muscled phenotype in different breeds. The number of mutations found suggest that myostatin is highly variable within beef cattle. Variations that alter the structure of the gene product such that the protein is inactivated are associated with the most pronounced form of double-muscling as seen in the Belgian Blue. However, other mutations may have a less extreme affect on muscle development. While overt double-muscling gives rise to a high incidence of dystocia (calving difficulty), it is possible that some variants may give enhanced muscling, but with limited calving problems. We describe sequence analysis of the myostatin gene in ten beef breeds commonly used in the UK and show that the 11-bp deletion responsible for double-muscling in the Belgian Blue is also present in the South Devon cattle population. Allele frequencies and haplotypes in the South Devon and a polymerase chain reaction (PCR) based test for the deletion are described. PCR amplification across the deleted region provides a quick and effective test with clear identification of heterozygous individuals. We discuss our results with regard to the effect of genotype on phenotype and differences observed between the Belgian Blue and the South Devon.

Animals↗
PubMed2000

Risk factors for surgical wound infection and bacteraemia following coronary artery bypass surgery.

BACKGROUND: There has been no consensus from previous studies of risk factors for surgical wound infections (SWI) and postoperative bacteraemia for patients undergoing coronary artery bypass graft (CABG) surgery. METHODS: Data on 15 potential risk factors were prospectively collected on all patients undergoing CABG surgery during a 12-month period. RESULTS: Of 693 patients, 62 developed 65 SWI using the Centres for Disease Control definition: 23 were sternal wound infections and 42 were arm or leg wound infections at the site of conduit harvest. There were 19 episodes of postoperative bacteraemia. Multivariate analysis revealed that: (i) diabetes, obesity and previous cardiovascular procedure were independent predictors of SWI; and (ii) obesity was an independent risk factor for postoperative bacteraemia. CONCLUSIONS: These findings suggest that improved diabetic control and pre-operative weight reduction may result in a decrease in the incidence of SWI. But further prospective studies need to be undertaken to examine (i) whether the increased SWI risk in diabetes occurs with both insulin- and non-insulin-requiring diabetes, and whether improved peri-operative diabetes control decreases SWI; and (ii) what degree of obesity confers a risk of SWI and postoperative bacteraemia, and whether pre-operative weight reduction, if a realistic strategy in this patient group, results in a decrease in SWI.

Bacteremia↗
PubMed2000

A simplified method of harvesting and dilating the radial artery achieves acceptable clinical outcomes.

BACKGROUND: The recent successful revival of the radial artery as a coronary-bypass conduit has been attributed to a minimally traumatic harvesting technique without diathermy, combined with long-term oral calcium antagonist therapy. We describe a simplified technique of harvesting the radial artery, which reduces procurement time and maintains conduit relaxation. METHODS: Radial arteries were harvested using diathermy and topical glyceryl trinitrate-verapamil dilator solution. Postoperatively, intravenous glyceryl trinitrate, but no calcium antagonist was used. The clinical results in the first 100 consecutive patients receiving radial artery grafts (RA group), procured using this technique, were compared with a group of 100 patients receiving saphenous vein conduits (SV group) immediately prior to the introduction of the radial artery at our institution. RESULTS: There were no demographic differences between the two groups, other than the SV group being slightly older. There was one intraoperative death in each group. There was no difference in the rate of peri-operative myocardial infarction or length of stay in the intensive care unit. At a median follow-up time of 16 months for the RA group, and 25 months for the SV group, the survival rates were 97 and 94%, respectively. All survivors were in the New York Heart Association class I. In the SV group, two postoperative angioplasties were performed. CONCLUSIONS: These early results suggest that this method of procuring the radial artery using diathermy, glyceryl trinitrate and no postoperative calcium antagonists, is rapid, safe and effective. The continued use of this technique is justified, while awaiting the results of long-term angiographic studies.

Aged↗
PubMed2000

Outcomes of coronary artery bypass grafting: a 3 year analysis using the Society of Thoracic Surgeons Database.

BACKGROUND: Accurate risk factor analysis is a critical element in contemporary cardiac surgical practice. In the USA, the Society of Thoracic Surgeons Database allows institutions and individual surgeons to carry out detailed patient risk assessment and to review their cardiac surgical outcomes in a comparative fashion. METHODS: To evaluate outcomes of isolated coronary artery bypass grafting, data from all patients operated upon at the Alfred Hospital, Melbourne, Australia, over a 3 year period were entered into the Society of Thoracic Surgeons Database. RESULTS: Our results (mortality and morbidity) compared favourably with those contained within this large international database. CONCLUSION: It is hoped that a similar Australasian database can be established to facilitate a meaningful local risk assessment and a comparative analysis of outcomes of cardiac surgical procedures.

Journal Article↗
PubMed2000

Prostaglandin E2-induced sensitization of bradykinin-evoked responses in rat dorsal root ganglion neurons is mediated by cAMP-dependent protein kinase A.

Primary cultures of neonatal rat dorsal root ganglion (DRG) neurons were used to examine the mechanisms underlying both the direct activation and the sensitization of sensory neurons by prostanoids. Prostaglandin E2 (PGE2) elevated cytosolic calcium concentration ([Ca2+]i) in a subpopulation of small (< 19 microm) diameter, capsaicin-sensitive DRG neurons. PGE2 also stimulated substance P (SP) release from DRG cultures. In contrast to bradykinin, PGE2 did not stimulate phosphoinositidase C (PIC) and the PGE2-evoked increase in [Ca2+]i was dependent on extracellular calcium. Pre-treatment with PGE2 potentiated bradykinin-evoked increases in [Ca2+]i in small diameter neurons and increased the number of cells that responded to low concentrations of bradykinin. A similar effect was seen with prostaglandin I2 (PGI2) but not prostaglandin F2alpha (PGF2alpha). PGE2 pretreatment also potentiated bradykinin-evoked release of SP, inducing a leftward shift in the bradykinin concentration-response curve and an increase in the maximum response. PGE2 stimulated adenylyl cyclase activity in DRG cultures, at concentrations and times consistent with those required to observe both the direct and sensitizing effects of the prostanoid on [Ca2+]i responses. Furthermore, the direct and sensitizing effects of PGE2, on both [Ca2+]i responses and SP release, were mimicked by the membrane permeant cAMP analogue dibutyryl cAMP and inhibited by H89, an inhibitor of cAMP-dependent protein kinase A (PKA). These observations are consistent with the hypothesis that both direct activation and sensitization of sensory neurons by prostanoids, such as PGE2, are mediated by PKA-dependent phosphorylation mechanisms.

Adenylyl Cyclases↗
PubMed2000

Reduced 15-lipoxygenase-2 immunostaining in prostate adenocarcinoma: correlation with grade and expression in high-grade prostatic intraepithelial neoplasia.

Arachidonic acid (AA) metabolites are implicated in the oncogenesis of several tumors, including prostate cancer. 15-Lipoxygenase-2 (15-LOX-2) is a novel AA-metabolizing enzyme with a limited tissue distribution, which includes prostate, lung, skin, and cornea. Previous studies have shown that 15-LOX-2 is present in benign prostate secretory cells and reduced in prostate adenocarcinoma and that production of the 15-LOX-2 metabolite 15S-hydroxyeicosatetraenoic acid is reduced in malignant compared with benign prostate. The objective of this study was to determine the frequency with which 15-LOX-2 immunostaining is reduced in prostate carcinoma and to correlate reduced expression with tumor differentiation (grade) and other pathologic parameters in radical prostatectomy specimens. Paraffin immunoperoxidase with a polyclonal antibody specific for 15-LOX-2 was performed on tumors and benign portions from 70 cases, and the percentage of tumor immunostaining for 15-LOX-2 was assessed. Whereas uniform 15-LOX-2 immunostaining was observed in secretory cells of benign glands, it was markedly reduced or absent in most adenocarcinomas: 23 of 70 tumors showed completely absent 15-LOX-2 immunostaining, and 45 of 70 cases showed negative immunostaining in more than 50% of the tumor. The extent of reduced 15-LOX-2 immunostaining correlated with tumor differentiation, with retained expression particularly in Gleason score 5 tumors versus a significant reduction of 15-LOX-2 in higher-grade tumors (mean +/- SD tumor 15-LOX-2 positive: Gleason score 5 = 67%+/-30%, Gleason score 6 = 16%+/-30%, Gleason score 7 = 23%+/-28%, Gleason score > or =8 = 41%+/-46%). In 16 cases with multifocal tumors or different foci of the same tumor with different grades, the higher-grade foci had significantly reduced 15-LOX-2 expression compared with the lower-grade foci. In peripheral zone tumors without complete loss of 15-LOX-2 expression, there was a significant inverse relationship between 15-LOX-2 immunostaining and tumor volume. There was not a significant correlation between 15-LOX-2 immunostaining and serum PSA or pathologic stage. In a subset of 27 cases, 15-LOX-2 expression in high-grade prostatic intraepithelial neoplasia (HGPIN) glands was significantly reduced compared with benign glands. These data show that in contrast to the uniform expression of 15-LOX-2 in differentiated secretory cells of benign prostate, reduced 15-LOX-2 is a common alteration in prostate carcinoma, and this correlates with tumor cell differentiation. That reduced expression is seen in HGPIN suggests that this may be an early alteration in carcinoma development.

Adenocarcinoma↗
PubMed2000

Certainty and uncertainty in genetic counselling: a qualitative case study.

This study examines the communication that occurs during routine genetic counselling sessions. It involves the qualitative analysis of nine consultations with one member of a clinical genetics team. The consultations were characterised by a contrast between the sense of certainty apparent in how the clinicians talked about the power and promise of the new genetics and the uncertainty communicated regarding the actual information produced by genetic tests and their limitations in solving people's problems. There was also a contrast between how the clinician seemed to control the format and agenda of the consultation and the apparently uncontrollable personal and social implications of the topics discussed. We speculate that this may be explained in terms of the clinician giving some order and certainty in an area of inherent uncertainty, and where great promises are as yet unrealised.

Communication↗
PubMed2000

Tissue characterization using magnetic resonance elastography: preliminary results.

The well-documented effectiveness of palpation as a diagnostic technique for detecting cancer and other diseases has provided motivation for developing imaging techniques for noninvasively evaluating the mechanical properties of tissue. A recently described approach for elasticity imaging, using propagating acoustic shear waves and phase-contrast MRI, has been called magnetic resonance elastography (MRE). The purpose of this work was to conduct preliminary studies to define methods for using MRE as a tool for addressing the paucity of quantitative tissue mechanical property data in the literature. Fresh animal liver and kidney tissue specimens were evaluated with MRE at multiple shear wave frequencies. The influence of specimen temperature and orientation on measurements of stiffness was studied in skeletal muscle. The results demonstrated that all of the materials tested (liver, kidney, muscle and tissue-simulating gel) exhibit systematic dependence of shear stiffness on shear rate. These data are consistent with a viscoelastic model of tissue mechanical properties, allowing calculation of two independent tissue properties from multiple-frequency MRE data: shear modulus and shear viscosity. The shear stiffness of tissue can be substantially affected by specimen temperature. The results also demonstrated evidence of shear anisotropy in skeletal muscle but not liver tissue. The measured shear stiffness in skeletal muscle was found to depend on both the direction of propagation and polarization of the shear waves.

Animals↗
PubMed2000

Inhibition of interferon, cytokine, and lymphocyte proliferative responses in elite swimmers with altitude exposure.

To determine the immunologic consequences of athletic training at altitude, blood samples were taken at rest from 10 swimmers and 8 control nontraining but altitude-exposed members of the 1996 Australian Olympic Swimming Team, near the start and completion of a 21-day training camp at 2102 m. Blood leukocyte numbers dropped in both groups (p < 0.05), with the decrease greater in the swimmers (-38% swimmers, -3% controls). Concanavalin A (ConA)-induced blastogenesis decreased in both groups (p < 0.01), but the drop was greater in the control group (-32% swimmers, -56% controls, p < 0.05). Lipopolysaccharide (LPS)-induced blastogenesis more than doubled in both groups (281% swimmers, 249% controls, p < 0.01). Increases in mitogen-induced interleukin-1beta (IL-1beta), IL-4, and interferon-gamma (IFN-gamma) production and a decrease in IL-2 levels were observed in both groups after altitude exposure (all p < 0.05). The percentage of cells expressing HLA-DR fell (-33% swimmers, -20% controls, p < 0.01), whereas those expressing CD-4 expression increased (16% swimmers only, p < 0.01). Although training at medium-level altitude alters some immunologic parameters, the training-induced changes may be secondary to those induced by altitude alone.

Adaptation, Physiological↗
PubMed2000

Disabled people and professionals differ in their perceptions of rehabilitation needs.

BACKGROUND: This study set out to explore whether there are systematic differences in unmet needs for rehabilitation services and resources as identified by disabled people and nominated key professionals. METHODS: A cross-sectional interview survey of 87 pairs of community-dwelling disabled people (aged 16-65) and their nominated key professionals was conducted in southern England. The Southampton Needs Assessment Questionnaire (SNAQ) was used to examine unmet needs and the Office of Population Censuses and Surveys (OPCS) Disability and Severity Scale to examine level of disability. RESULTS: Eighty-seven pairs of disabled people and their nominated key professionals participated. People were severely disabled (median OPCS score 8; interquartile range 6-9). Disabled participants reported significantly more unmet needs than did professionals. There was zero concordance on identified unmet needs between disabled participants and professionals in 56 per cent of cases. Concordance between disabled participants and professionals was significantly better if the disabled participant had reported more unmet needs. There was a trend for general practitioners to be poorer at reporting disabled participants' needs than other professionals. There was fair agreement between disabled participants and professionals in five areas of unmet need only (in descending order): adaptations, physiotherapy, equipment, assistance with 'non-care' activities and the use of a day centre. In all the other areas of unmet need the agreement was poor. CONCLUSIONS: Needs for rehabilitation services and resources (for disabled people) are perceived differently by disabled people and professionals. Until we know who is right about rehabilitation needs, it is important to determine both users' and providers' views when planning and commissioning services.

Adolescent↗
PubMed2000

Interface between vascular dementia and Alzheimer syndrome. Nosologic redefinition.

Vascular dementia is redefined so as to include noninfarct vascular dementia: vascular dementia caused by underlying vascular factors other than cerebral infarction. Data are presented that bring into focus the interface between vascular dementia and Alzheimer syndrome, and the ambiguous transition between multifocality and diffuse or generalized disease. By cross-cutting both stroke and nonstroke vascular groups, arteriosclerosis, abnormal blood pressure, abnormal electrocardiogram, and other vascular factors are implicated in the distal causality of both infarct and noninfarct vascular dementia.

Aged↗
PubMed2000

Imbalance of stromelysin-1 and TIMP-1 in the mucosal lesions of children with inflammatory bowel disease.

BACKGROUND: Degradation of the extracellular matrix and ulceration of the mucosa are major features of inflammatory bowel disease (IBD). One of the most important enzymes in degrading the matrix and produced in excess by cytokine activated stromal cells, is stromelysin-1. The activity of stromelysin-1 is controlled by tissue inhibitor of metalloproteinase (TIMP-1), its natural inhibitor. In model systems excess stromelysin-1 produces mucosal degradation. METHODS: Quantitative competitive RT-PCR was used to analyse stromelysin-1 and TIMP-1 transcripts; western blotting was used to measure the amount of stromelysin-1 and TIMP-1 protein in biopsy samples from children with IBD. RESULTS: In biopsies from patients with active Crohn's disease (n=24), ulcerative colitis (n=23), and controls (n=16), TIMP-1 transcripts and protein were abundant and unchanged. Stromelysin-1 transcripts and protein were markedly elevated in mucosal biopsies obtained from inflamed sites of patients with active IBD but were not elevated in adjacent endoscopically normal mucosa (n=10). Elevated levels of stromelysin-1 transcripts in active Crohn's disease (n=5) returned to normal levels following treatment with enteral nutrition. CONCLUSIONS: Stromelysin-1 is markedly overexpressed at inflamed sites in patients with IBD whereas TIMP-1 remains unaltered. Excess stromelysin-1 is likely to be responsible for loss of mucosal integrity in IBD.

Blotting, Western↗