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Biomedical subjects

J A Smith

Publications and source records attributed to J A Smith.

At least 163 records · Page 9Linked to original sources
PubMed1999

Immunocytochemical localization of P2X3 purinoceptors in sensory neurons in naive rats and following neuropathic injury.

P2X3 purinoceptor cellular distribution was studied in rat sensory neurons in naive animals and following peripheral nerve injury using immunohistochemical methods. Specific antiserum was raised in rabbits and characterized by Western blot, absorption assays and labeling of recombinant receptors. In naive animals, P2X3 immunoreactivity was present predominantly in a subpopulation of small-diameter sensory neurons in dorsal root ganglia. In the spinal cord, immunoreactivity was observed in the superficial laminae of the dorsal horn. Following a chronic constriction injury to the sciatic nerve, the number of P2X3 positive small and medium diameter neurons increased in dorsal root ganglia when compared with sham-operated animals. In addition, the spinal cord immunoreactivity increased in magnitude on the side ipsilateral to the ligated nerve, consistent with up-regulation of receptors in presynaptic terminals of the primary sensory neurons.

Animals↗
PubMed1999

Once-daily budesonide inhalation suspension for the treatment of persistent asthma in infants and young children.

BACKGROUND: Inhaled glucocorticosteroids (GCS) are the most effective long-term controller medications for the treatment of persistent asthma. Currently, however, available delivery devices limit their use in young children. A nebulized formulation of budesonide has been developed to address the needs of infants and young children. OBJECTIVE: To evaluate the efficacy and safety of once-daily budesonide inhalation suspension in children 6 months to 8 years old with mild persistent asthma not on inhaled GCS. METHODS: Three hundred fifty-nine children were randomized to receive once-daily budesonide inhalation suspension (0.25 mg, 0.50 mg, or 1.0 mg) or placebo via a Pari LC-Jet Plus nebulizer for 12 weeks. Efficacy assessments included nighttime/daytime asthma symptoms, pulmonary function (subset of patients), rescue medication use, and treatment discontinuations. Safety was based on adverse events and assessment of HPA-axis function. RESULTS: Demographics, baseline characteristics, asthma symptoms, and pulmonary function were similar across treatment groups. Mean nighttime/daytime asthma symptom scores were 1.19 +/- 0.63 and 1.34 +/- 0.53, respectively. Mean duration of asthma was 36.3 months and mean FEV1 was 81.3% of predicted with 27.7% reversibility. Following 12 weeks of treatment, all budesonide inhalation suspension doses produced significant improvements in nighttime/daytime symptoms (P < or = .049) and significant decreases in rescue medication use (P < or = .038) compared with placebo. Significant improvements (P < or = .044) in FEV1 were observed in the 0.5- and 1.0-mg budesonide inhalation suspension groups. There were no differences between doses of budesonide inhalation suspension. Adverse events and basal and ACTH-stimulated cortisol levels were similar among all groups. CONCLUSION: Once-daily administration of budesonide inhalation suspension was well tolerated and effective for the treatment of mild persistent asthma in infants and young children not adequately controlled with bronchodilators or non-GCS antiinflammatory treatments.

Administration, Inhalation↗
PubMed1999

Antibiotic use in patients admitted with acute exacerbations of chronic obstructive pulmonary disease.

The objective of this report was to document the pattern of initial antibiotic prescribing in acute exacerbations of chronic obstructive pulmonary disease (COPD) in a hospital setting. All episodes of acute exacerbation of COPD, as diagnosed by the admitting doctor, in one hospital in the period January to May 1996, were identified. Case notes were reviewed retrospectively. Cases of radiographic pneumonia, bronchiectasis and incorrectly coded admissions were excluded. Symptoms, microbial cultures and initial antibiotic therapies were recorded. One hundred and fifty-nine patient episodes were identified; 40 were excluded yielding a sample of 119. Nineteen case notes were unavailable leaving a sample of 100 (84%) episodes. Eighty were treated with antibiotics on admission; amoxycillin was the most frequently prescribed, in 46 (58%) episodes. Of the antibiotic treated group, 42 (53%) patients were given dual therapy, most commonly a macrolide antibiotic with either amoxycillin or a cephalosporin. Intravenous treatment was used in 22 (28%) cases. The duration of intravenous treatment was >48 h in 12 (15%) cases. A total of 76 sputum samples were analysed from 55 patient episodes: 34 (45%) were culture positive. In 15 (27%) patient episodes, antibiotic therapy was changed or instituted on the basis of culture results. These data suggest that antibiotic treatment is not optimal, with overuse of antibiotics, especially intravenous and dual therapy.

Aged↗
PubMed1999

Is invasive anesthetic monitoring necessary during radical prostatectomy?

The purpose of this study was to obtain objective information on the necessity of invasive anesthetic monitoring during radical prostatectomy. We reviewed retrospectively the charts of 257 patients undergoing radical prostatectomy on an established pathway which did not include the intraoperative use of an arterial line or central venous catheter. Outcome measures including intraoperative vital signs, cardiac arrhythmias, blood loss and fluid management were assessed. In particular, we sought to determine situations in which insertion of monitoring devices was required because of an unanticipated intraoperative event. The patient ages ranged from 40 to 75 y with a mean of 60.3 y. The mean estimated blood loss was 546.9 cm(3) (median 500 cm(3)). Thirty-eight patients had a measured intraoperative systolic blood pressure of <90 mmHg, but no hypotensive episodes required any treatment other than fluid administration. A single patient required pharmacologic therapy for hypertension. One patient received intravenous lidocaine because of premature ventricular contractions, but no other arrhythmias were observed. No patient required intraoperative insertion of an arterial line or central venous catheter. These data provide objective evidence for the abandonment of routine use of central venous catheters or arterial lines during radical prostatectomy. This avoids not only the expense of these maneuvers, but also the potential morbidity of unnecessary invasive medical procedures.

Journal Article↗
PubMed1999

Cervical intraepithelial neoplasia grade III (CIN III) and invasive cervical carcinoma: the yawning gap revisited and the treatment of risk.

In a 3-year study of the population of Southampton and south-west Hampshire there were 10 times as many cases of CIN III compared with invasive squamous carcinoma (700 compared with 70). The peak incidence of CIN III per 1000 screened women years was in those aged 25-29 years, which was 20 years earlier than the peak incidence of invasive cervical cancer per 1000 women years at risk. Ninety percent of CIN III was diagnosed in women under 50 years. There were 14 cases of cervical glandular intraepithelial neoplasia grade III (CGIN III), three coexisting with CIN III, all in women aged under 50 years: the gap between intraepithelial and invasive lesions was not seen for glandular neoplasia. Although referral was for at least moderate dyskaryosis in 86.8% of women with CIN III or CGIN III, most had been screened previously, either having had mild abnormalities requiring repeat cytology (39.8%) or negative cytology (34.5%). Only 12 women aged > or = 50 years had previous negative cytology: 21.4% compared with 35.6% of women aged < 50 years (P = 0.034). The results of this study suggest that the best opportunity for preventing invasive squamous cell carcinoma lies in screening women aged 20-39 years when the incidence of CIN III in the screened population is highest and before the peak incidence of invasive disease. The results also indicate the importance of repeated screening and follow up of minor cytological abnormalities in the detection of CIN III. The benefit of screening must be regarded as a treatment of risk, since it is almost certain that a high proportion of CIN III regresses or persists unchanged.

Adolescent↗
PubMed1999

Male reproductive success in a promiscuous mammal: behavioural estimates compared with genetic paternity.

Molecular techniques have enabled behavioural ecologists to reassess mating systems from a genetic perspective. Studies of paternity frequently reveal that mating behaviour does not always reflect parentage, and may bring to light alternative mating tactics. Here we present a comparison of behavioural and genetic measures of male reproductive success in a mammalian mating system in which both sexes are highly promiscuous. Rather than having a stable harem social structure, Soay rams (Ovis aries) on the island of Hirta, St Kilda, UK usually consort with individual oestrous ewes sequentially. Not all matings occur between consort pairs, however, and ewes have been seen to mate with up to 10 different rams on the same day. Using locus-specific polymorphism at five protein and 10 microsatellite DNA loci, we determined paternity for 236 lambs born into three cohorts, and compared paternity with estimates of mating success derived from more than one census of rutting behaviour. The correlation between the number of ewes with which each ram was witnessed in consort and the number of paternities assigned was positive and statistically significant, and rams that were observed in consort with a ewe were 18 times more likely to have sired her offspring than other candidate rams. However, most lambs (73%) were not sired by a ram seen in consort with the oestrous mother. Many juveniles, yearlings and some adult rams were rarely seen in consort with ewes, yet were assigned a significant number of paternities. These results suggest that mating tactics differ between age groups, and that alternative mating strategies among adults that do not involve forming consorts with many females also confer mating success. For these reasons, census-based observations of consort associations between individuals cannot be used to accurately estimate individual male reproductive success in this population.

Animals↗
PubMed1999

Density-dependent variation in lifetime breeding success and natural and sexual selection in Soay rams.

Variation in male lifetime breeding success (LBS) is central to understanding selection, yet it has rarely been measured in natural populations of large mammals. Here, we first describe variation in the opportunity for selection in cohorts of Soay rams (Ovis aries) on the archipelago of St. Kilda, Scotland, that were born during years of varying population density. Variation in LBS is closely coupled with demography, as rams born in years of low density following population crashes enjoy greater LBS than do those born in high-density years. Paradoxically, the opportunity for selection was greatest in the largest cohorts, those born in years of high population density, owing to low juvenile breeding success and overwinter survival. Variation in longevity and the contribution of nonbreeders were the most important components of the total variance in LBS in cohorts born in years of high density, while variation in fecundity was more important in cohorts born in low-density years. The opportunity for sexual selection is thus stronger in cohorts born in low-density years, as many rams in these cohorts survive to compete for mates as adults in subsequent ruts. Variation in population density in the year of birth also influenced the intensity of selection. Individuals born in years of high population density underwent strong natural selection in favor of longer hindlimbs over their first winter. In contrast, in cohorts born in low-density years, there was no natural selection on hindlimb in the first year of life. Longer hindlimbs were associated with increased fecundity over the entire lifetime of individuals born in low-density years. Natural and sexual selection thus act on the same trait in the same direction at different life-history stages in Soay rams, depending on the population density experienced in the year of birth.

Journal Article↗
PubMed1999

Exercise and cellular innate immune function.

Epidemiological evidence suggests a link between the intensity of exercise and infectious and neoplastic disease. One likely way by which exercise exerts its effect on cancer and infection is by altering the function of the immune system. Cells of the innate immune system (i.e., macrophage [Mphi], natural killer [NK] cell, and polymorphonuclear neutrophils [PMN]) are first-line defenders against cancer and infectious disease by nature of their phagocytic, cytolytic, and antimicrobial properties. The purpose of this review is to define the role of cells of the innate immune system (i.e., Mphi, PMN, and NK cells) in infection and cancer, present current information regarding the effects of acute and chronic exercise on the quantification and functional activities of these cells, and briefly to discuss potential mechanisms as to how exercise affects these cells and describe how these changes may potentially affect susceptibility to infection and cancer. The effects of exercise on the number, functions, and characteristics of cells of the innate immune system are complex and are dependent several factors, including 1) the cell function or characteristic being analyzed; 2) the intensity, duration and chronicity of exercise; 3) the timing of measurement in relation to the exercise bout; 4) the dose and type of immunomodulator used to stimulate the cell in vitro or in vivo; and 5) the site of cellular origin. Further studies are needed to determine whether the exercise-induced changes in immune function alter incidence or progression of disease. Likewise, the mechanisms as to how exercise alters innate immune function are as yet unresolved.

Exercise↗
PubMed1999

Greater erythrocyte deformability in world-class endurance athletes.

Because athletes during endurance events require rapid uptake of oxygen, the ability of red blood cells (RBC) to move through capillaries may limit performance. Using ektacytometry, we determined whether RBC deformability (RCD) differed between elite road cyclists (n = 9) and sedentary controls (n = 5). Density profiles and standard hematological measurements were also performed. The deformability index (DI) was higher in the cyclists (0.723 +/- 0.027) compared with that in controls (0.619 +/- 0.040, P < 0.001). Cyclists also had a larger percentage of low-density RBCs (P < 0. 001), and mean cell volume (MCV) was also higher (P = 0.013). These findings are indicative of a larger proportion of "young" RBCs in the blood of elite cyclists and provide further evidence that the turnover of RBCs in endurance athletes is higher than in the general population. With a younger more deformable RBC population and providing the destruction does not exceed replacement, performance potential should be enhanced. Furthermore, examination of factors that contribute to increased RBC turnover in athletes may help us understand the mechanisms that cause RBC aging.

Adult↗
PubMed1999

Generic health status measures are unsuitable for measuring health status in severely disabled people.

OBJECTIVES: To assess the perceived health status of disabled people. DESIGN: Perceived health status was evaluated with the Short Form 36 Health Survey (SF-36) and the Nottingham Health Profile as part of a needs assessment project exploring systematic differences in unmet needs for rehabilitation as perceived by disabled people, carers and professional staff. Disabled participants completed these health status questionnaires, as part of a face-to-face interview in participants' own homes. SUBJECTS: Ninety-two disabled people aged 16-65, recruited into the study from two disability registers. OUTCOME MEASURES: The Office of Population Censuses and Surveys (OPCS) Disability Severity Scale, Nottingham Health Profile, SF-36. RESULTS: Ninety-six disabled people took part in this study. Four were later excluded because of overwhelming communication difficulties. Median OPCS category was 8 (interquartile range 6-9.75). The pain and physical mobility domains of the Nottingham Health Profile were not completed by 46/92 participants (50%) because many questions referred to activities that these people could not perform, particularly walking. The physical functioning domain of the SF-36 showed severe floor effects. It was not therefore possible to use these measures to test the effectiveness of services provided to disabled people, particularly in the areas of physical functioning and pain. CONCLUSIONS: There is a continued need to develop and test instruments that can measure the outcomes of rehabilitation in severely disabled populations.

Adolescent↗
PubMed1999

Differential modulation of the tyrosine phosphorylation state of the insulin receptor by IRS (insulin receptor subunit) proteins.

In response to insulin, tyrosine kinase activity of the insulin receptor is stimulated, leading to autophosphorylation and tyrosine phosphorylation of proteins including insulin receptor subunit (IRS)-1, IRS-2, and Shc. Phosphorylation of these proteins leads to activation of downstream events that mediate insulin action. Insulin receptor kinase activity is requisite for the biological effects of insulin, and understanding regulation of insulin receptor phosphorylation and kinase activity is essential to understanding insulin action. Receptor tyrosine kinase activity may be altered by direct changes in tyrosine kinase activity, itself, or by dephosphorylation of the insulin receptor by protein-tyrosine phosphatases. After 1 min of insulin stimulation, the insulin receptor was tyrosine phosphorylated 8-fold more and Shc was phosphorylated 50% less in 32D cells containing both IRS-1 and insulin receptors (32D/IR+IRS-1) than in 32D cells containing only insulin receptors (32D/IR), insulin receptors and IRS-2 (32D/IR+IRS-2), or insulin receptors and a form of IRS-1 that cannot be phosphorylated on tyrosine residues (32D/IR+IRS-1F18). Therefore, IRS-1 and IRS-2 appeared to have different effects on insulin receptor phosphorylation and downstream signaling. Preincubation of cells with pervanadate greatly decreased protein-tyrosine phosphatase activity in all four cell lines. After pervanadate treatment, tyrosine phosphorylation of insulin receptors in insulin-treated 32D/IR, 32D/ IR+IRS-2, and 32D/IR+IRS-1F18 cells was markedly increased, but pervanadate had no effect on insulin receptor phosphorylation in 32D/IR+IRS-1 cells. The presence of tyrosine-phosphorylated IRS-1 appears to increase insulin receptor tyrosine phosphorylation and potentially tyrosine kinase activity via inhibition of protein-tyrosine phosphatase(s). This effect of IRS-1 on insulin receptor phosphorylation is unique to IRS-1, as IRS-2 had no effect on insulin receptor tyrosine phosphorylation. Therefore, IRS-1 and IRS-2 appear to function differently in their effects on signaling downstream of the insulin receptor. IRS-1 may play a major role in regulating insulin receptor phosphorylation and enhancing downstream signaling after insulin stimulation.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Towards a relational self: social engagement during pregnancy and psychological preparation for motherhood.

This study works towards a theoretical model of the relational self derived from the intensive examination of a small number of case studies of women going through their first pregnancy. The study is idiographic, grounded in the women's own accounts of the experience, and it is primarily qualitative. It employs interviews, diaries, repertory grids and interpretative phenomenological analysis. The theory argues that pregnancy can accentuate the symbiotic relation of one's perception of self and others, and that this aids psychological preparation for mothering. Increasing contact with key others can be psychologically informative: the woman may perceive herself as becoming more like key other(s); close involvement with existing family can facilitate the woman's preparation for taking on the new role of mother. The model is explicated with illustrations from the women's accounts. It is then discussed in relation to the existing literature.

Adult↗
PubMed1999

Aortic calcification contributing to bone densitometry measurement.

A 75-yr-old glucocorticoid-dependent asthmatic male had a bone mineral density study to assess possible osteoporosis prior to initiating therapy. A radiograph of the lumbar spine revealed an asymmetrical compression of the second lumbar vertebra, marked scoliosis, vertebral osteopenia, and a highly calcified abdominal aorta. Bone mineral density (dual X-ray absolptiometry [DXA]) revealed low bone mass in L2-L4 and a markedly abnonrnal pattern, with a linear central density representing a calcified aorta. Posterior-anterior measurements of the midlumbar region with and without the overlying aorta indicated that the calcified vessel contributed up to 33% of the measured density. This was a far higher contribution than reported in other studies. Lateral DXA measurements of the L2 vertebra and the overlying aorta were performed to validate this finding. The density of the L2 vertebra was 0.215 g/cm(2), and that of the overlying calcified aorta was 0. 210 g/cm(2). This case suggests that aortic calcifications may contribute sign)ficantly to overall lumbar bone density and, unless recognized, can inadvertently lead to misclassification of osteoporosis.

Absorptiometry, Photon↗
PubMed1999

Continuous quality improvement for point-of-care testing using background monitoring of duplicate specimens.

CONTEXT: Despite compliance with quality control standards, concerns remain as to the accuracy and reliability of point-of-care testing. OBJECTIVE: To assess a practical method for quality improvement using the context in which point-of-care testing is done. DESIGN: Quality measures for point-of-care testing, making use of natural duplication of results obtained by other testing methods, were used to monitor testing quality and evaluate quality improvement interventions. SETTING: Five adult intensive care units (total of 88 beds) in a large academic medical center, using point-of-care testing for blood gases, electrolytes, and hematocrit levels. PARTICIPANTS: Nurses performing bedside testing and laboratory personnel assigned the responsibility for supervising their performance. INTERVENTIONS: Quality of testing was monitored continuously, and, where problems were identified, training and support interventions implemented, and their effects evaluated. MAIN OUTCOME MEASURES: Improvement in correlation coefficients and regression parameters of point-of-care hematocrit and potassium testing results compared with contemporaneous results from the core laboratory. RESULTS: The initial survey found point-of-care potassium levels were tightly correlated with core laboratory results (r = 0.958). Baseline correlation coefficients and regression parameters for point-of-care hematocrit levels compared with core laboratory values varied widely from unit to unit. The intensive care units with the highest variances of bedside vs core laboratory testing received targeted interventions. Follow-up yielded evidence of dramatic improvement; 1 unit experienced an increase in correlation from 0.50 to 0.95. CONCLUSIONS: The findings suggest that, when point-of-care testing is highly dependent on operator technique, targeted interventions can resolve problems and provide reliable results at the bedside.

Blood Gas Analysis↗
PubMed1999

Bladder cancer clinical guidelines panel summary report on the management of nonmuscle invasive bladder cancer (stages Ta, T1 and TIS). The American Urological Association.

PURPOSE: The American Urological Association convened the Bladder Cancer Clinical Guidelines Panel to analyze the literature regarding available methods of treating nonmuscle invasive bladder cancer, and to make practice policy recommendations based primarily on treatment outcomes data. MATERIALS AND METHODS: The panel searched the MEDLINE database for all articles related to nonmuscle invasive bladder cancer published from 1966 to January 1998. Outcomes data were extracted from articles accepted after panel review and meta-analyzed to produce comparative probability estimates for alternative treatments. RESULTS: All of the intravesical agents (thiotepa, bacillus Calmette-Guerin, mitomycin C and doxorubicin) when used as adjuvant therapy after transurethral resection resulted in a lower probability of recurrence compared to resection alone. However, there is no evidence that intravesical therapy affects long-term progression. CONCLUSIONS: For patients with no prior intravesical therapy adjuvant intravesical chemotherapy or immunotherapy is a treatment option after endoscopic removal of low grade Ta bladder cancers. Intravesical instillation of bacillus Calmette-Guerin or mitomycin C is recommended for carcinoma in situ, and after endoscopic removal of T1 and high grade Ta tumors.

Humans↗