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Biomedical subjects

A Smith

Publications and source records attributed to A Smith.

At least 253 records · Page 14Linked to original sources
PubMed2001

NadN and e (P4) are essential for utilization of NAD and nicotinamide mononucleotide but not nicotinamide riboside in Haemophilus influenzae.

Haemophilus influenzae has an absolute requirement for NAD (factor V) because it lacks almost all the biosynthetic enzymes necessary for the de novo synthesis of that cofactor. Factor V can be provided as either nicotinamide adenosine dinucleotide (NAD), nicotinamide mononucleotide (NMN), or nicotinamide riboside (NR) in vitro, but little is known about the source or the mechanism of uptake of these substrates in vivo. As shown by us earlier, at least two gene products are involved in the uptake of NAD, the outer membrane lipoprotein e (P4), which has phosphatase activity and is encoded by hel, and a periplasmic NAD nucleotidase, encoded by nadN. It has also been observed that the latter gene product is essential for H. influenzae growth on media supplemented with NAD. In this report, we describe the functions and substrates of these two proteins as they act together in an NAD utilization pathway. Data are provided which indicate that NadN harbors not only NAD pyrophosphatase but also NMN 5'-nucleotidase activity. The e (P4) protein is also shown to have NMN 5'-nucleotidase activity, recognizing NMN as a substrate and releasing NR as its product. Insertion mutants of nadN or deletion and site-directed mutants of hel had attenuated growth and a reduced uptake phenotype when NMN served as substrate. A hel and nadN double mutant was only able to grow in the presence of NR, whereas no uptake of NMN was observed.

Bacterial Outer Membrane Proteins↗
PubMed2001

Comparative performance of herpes simplex virus type 2-specific serologic assays from Meridian Diagnostics and MRL diagnostics.

MRL Diagnostics and Meridian Diagnostics have recently designed herpes simplex virus type 2 (HSV-2)-specific enzyme immunoassays for HSV-2 antibody detection. Blood donor sera were assayed for HSV-2 antibodies by both methods. The sensitivity, specificity, and efficiency were 97.9, 95.4, and 95.9% for the MRL assay and 83.2, 98.2, and 95.5% for the Meridian assay, respectively.

Antibodies, Viral↗
PubMed2001

Factors associated with elevated intraocular pressure in eyes with iris melanoma.

AIM: To identify clinical factors associated with secondary elevated intraocular pressure (IOP) in eyes with iris malignant melanoma METHODS: A retrospective case series of 169 consecutive patients with microscopically confirmed iris malignant melanoma. The main outcome measure was the presence of tumour induced secondary elevated IOP. Cox proportional regression models were used to calculate the relation of clinical features to elevated IOP. RESULTS: Of 169 patients with microscopically proved iris melanoma, 50 (30%) presented with tumour induced secondary elevated IOP. The mean pressure in those eyes with elevated IOP at diagnosis was 33 mm Hg (median 31 mm Hg, range 23-65 mm Hg). The tumour configuration was nodular in 23 (46%) and diffuse in 27 (54%) with a mean base dimension of 7.4 mm and thickness of 2.0 mm. Invasion of the angle structures by melanoma seeds was visible for a mean of 7 clock hours (median 7, range 0-12 clock hours). The mechanism of elevated IOP was judged to be outflow obstruction from tumour invasion into the trabecular meshwork. There were no cases of neovascular glaucoma. The tumour was ultimately managed with enucleation in 30 patients (60%), local resection (iridectomy, iridocyclectomy, or iridocyclogoniectomy) in 11 (22%), and plaque radiotherapy in five (10%). In four cases (8%), observation of cytologically low grade tumour was the patient's preference. Using multivariate analysis, the clinical factors at initial evaluation associated with tumour induced secondary elevated IOP from iris melanoma included increasing extent of tumour seeding in the anterior chamber angle (p=0.01) and poor visual acuity at presentation (p=0.02). CONCLUSIONS: Microscopically confirmed iris melanoma demonstrates tumour related elevated IOP in 30% cases at the time of presentation, usually secondary to tumour involvement of the trabecular meshwork obstructing aqueous outflow. Enucleation is necessary in the majority of these patients (60%) as opposed to those cases without elevated intraocular pressure (18%).

Adolescent↗
PubMed2001

Pre-hospital aspirin for suspected myocardial infarction and acute coronary syndromes: a headache for paramedics?

OBJECTIVE: To ascertain the frequency with which paramedics follow protocols for the administration of aspirin to patients to whom an ambulance is called for chest pain associated with suspected ischaemic heart disease. METHODS: Ambulance services in England and Wales who had conducted a recent aspirin administration audit were identified through the National Clinical Effectiveness Programme for the Ambulance Service Association. Data were requested from each of these services with a 100% return rate. RESULTS: Nine services out of a total of 35 had collected appropriate data. The proportion of patients who were given aspirin by a paramedic varied from 11% to 74%. The range of proportions of patients receiving pre-hospital aspirin increased after adding those patients who had already received aspirin from an alternative health provider, to 19% to 78%. It is estimated that at least 15% to 74% of patients who should have been given aspirin by the various ambulance services did not receive it. The proportion of patients for whom aspirin was judged to be inappropriate ranged from 4% to 35%. The reason for these widely varying and generally poor levels of compliance is not known. However, the range of indications and contraindications to the administration of aspirin varied considerably by ambulance service. This also made the comparison of data from different sources difficult. CONCLUSIONS: Aspirin has been shown to be beneficial after a myocardial infarction and for other acute coronary syndromes. However, variances in the proportion of patients with suspected ischaemic heart disease given aspirin in different ambulance services indicates the need for a re-emphasis on the importance of this treatment. A standard protocol for all UK ambulance services should be devised that minimises the number of contraindications to aspirin and otherwise requires its administration to all patients with acute coronary syndromes or suspected myocardial infarction. Regular, standardised audits of compliance should also be conducted and their results widely disseminated.

Acute Disease↗
PubMed2001

Fatal disseminated fusarium infection in acute lymphoblastic leukaemia in complete remission.

Fusarium species are increasingly recognised as serious pathogens in the immunocompromised. The outcome in the context of persistent severe neutropenia has been almost universally fatal. However, there have been several case reports of successful treatment if neutrophil recovery can be achieved. This report presents the case of a fatality that occurred despite neutrophil recovery. A 67 year old man developed disseminated fusariosis during the neutropenic phase of induction chemotherapy for acute lymphoblastic leukaemia. Fusarium dimerum was isolated from blood cultures. This species is highly unusual and very few case reports exist in the literature. An initial response to amphotericin treatment coincided with neutrophil recovery but a subsequent relapse occurred, despite adequate neutrophil counts, which proved fatal. It is postulated that reseeding of the blood from an occult site, namely the right vitreum in this case, led to this secondary relapse despite achieving complete leukaemic remission.

Aged↗
PubMed2001

Assessment of antral grinding of a model solid meal with echo-planar imaging.

Mathematical modeling of how physical factors alter gastric emptying is limited by lack of precise measures of the forces exerted on gastric contents. We have produced agar gel beads (diameter 1.27 cm) with a range of fracture strengths (0.15-0.90 N) and assessed their breakdown by measuring their half-residence time (RT(1/2)) using magnetic resonance imaging. Beads were ingested either with a high (HV)- or low (LV)-viscosity liquid nutrient meal. With the LV meal, RT(1/2) was similar for bead strengths ranging from 0.15 to 0.65 N but increased from 22 +/- 2 min (bead strength <0.65 N) to 65 +/- 12 min for bead strengths >0.65 N. With the HV meal, emptying of the harder beads was accelerated. The sense of fullness after ingesting the LV meal correlated linearly (correlation coefficient = 0.99) with gastric volume and was independently increased by the harder beads, which were associated with an increased antral diameter. We conclude that the maximum force exerted by the gastric antrum is close to 0.65 N and that gastric sieving is impaired by HV meals.

Adult↗
PubMed2001

Is there an apparent diffusion coefficient threshold in predicting tissue viability in hyperacute stroke?

BACKGROUND AND PURPOSE: Rapid and precise identification of the penumbra is important for decision-making in acute stroke. We sought to determine whether an early and moderate decrease in the apparent diffusion coefficient (ADC) may help to identify, within the diffusion/perfusion (DWI/PWI) mismatch, those areas that will eventually evolve toward infarction. METHODS: We reviewed 48 patients not treated by thrombolytics who had a DWI/PWI within 6 hours after onset, with infarct evolution documented by follow-up magnetic resonance on days 2 to 4. We calculated absolute values for ADC and the ADC ratio (ADCr) in (1) the initial DWI hypersignal; (2) the final volume of the infarct, ie, the follow-up fluid-attenuated inversion recovery abnormalities; (3) the infarct growth (IGR) area; and (4) the oligemic area (OLI) that remained viable despite initial hemodynamic disturbance. We tested the value of the ADC to predict tissue outcome by using discriminant analysis. RESULTS: ADC values were marginally but significantly decreased in the IGR area (ADC 782+/-82x10(-6) mm(2)/s, ADCr 0.94+/-0.08) compared with mirror values (P=0.01) and with OLI (ADC 823+/-41x10(-6) mm(2)/s, ADCr 0.99+/-0.07; P=0.001). Of all quantitative DWI and PWI parameters, the ADCr best discriminated between IGR and OLI (F(1,50)=13.6, cutoff=0.97, 64% sensitivity, 92% specificity) and between the final volume of infarct and OLI (F(1,83)=219, cutoff=0.91, 91% sensitivity, 100% specificity). CONCLUSIONS: A simple approach based on ADC alone may allow the identification of tissue at risk of infarction in acute-stroke patients.

Acute Disease↗
PubMed2001

Predictors of successful extubation in neurosurgical patients.

A respiratory therapist-driven weaning protocol incorporating daily screens, spontaneous breathing trials (SBT), and prompts to caregivers has been associated with superior outcomes in mechanically ventilated medical patients. To determine the effectiveness of this approach in neurosurgical (NSY) patients, we conducted a randomized controlled trial involving 100 patients over a 14-mo period. All had daily screens of weaning parameters. If these were passed, a 2-h SBT was performed in the Intervention group. Study physicians communicated positive SBT results, and the decision to extubate was made by the primary NSY team. Patients in the Intervention (n = 49) and Control (n = 51) groups had similar demographic characteristics, illness severity, and neurologic injuries. Among all patients, 87 (45 in the Control and 42 in the Intervention group) passed at least one daily screen. Forty (82%) patients in the Intervention group passed SBT, but a median of 2 d passed before attempted extubation, primarily because of concerns about the patient's sensorium (84%). Of 167 successful SBT, 126 (75%) did not lead to attempted extubation on the same day. The median time of mechanical ventilation was 6 d in both study groups, and there were no differences in outcomes. Overall complications included death (36%), reintubation (16%), and pneumonia (9%). Tracheostomies were created in 29% of patients. Multivariate analysis showed that Glasgow Coma Scale (GCS) score (p < 0.0001) and partial pressure of arterial oxygen/fraction of inspired oxygen ratio (p < 0.0001) were associated with extubation success. The odds of successful extubation increased by 39% with each GCS score increment. A GCS score > or = 8 at extubation was associated with success in 75% of cases, versus 33% for a GCS score < 8 (p < 0.0001). Implementation of a weaning protocol based on traditional respiratory physiologic parameters had practical limitations in NSY patients, owing to concerns about neurologic impairment. Whether protocols combining respiratory parameters with neurologic measures lead to superior outcomes in this population requires further investigation.

Adolescent↗
PubMed2001

Resistance to Lyme disease in decorin-deficient mice.

Microbial adhesion to the host tissue represents an early, critical step in the pathogenesis of most infectious diseases. BORRELIA: burgdorferi, the causative agent of Lyme disease (LD), expresses two surface-exposed decorin-binding adhesins, DbpA and DbpB. A decorin-deficient (Dcn(-/-)) mouse was recently developed and found to have a relatively mild phenotype. We have now examined the process of experimental LD in Dcn(-/-) mice using both needle inoculation and tick transmission of spirochetes. When exposed to low doses of the infective agent, Dcn(-/-) mice had fewer Borrelia-positive cultures from most tissues analyzed than did Dcn(+/+) or Dcn(+/-) mice. When the infection dose was increased, similar differences were not observed in most tissues but were seen in bacterial colonization of joints and the extent of Borreila-induced arthritis. Quantitative PCR demonstrated that joints harvested from Dcn(-/-) mice had diminished Borrelia numbers compared with issues harvested from Dcn(+/+) controls. Histological examination also revealed a low incidence and severity of arthritis in Dcn(-/-) mice. Conversely, no differences in the numbers of Borreila-positive skin cultures were observed among the different genotypes regardless of the infection dose. These differences, which were observed regardless of genetic background of the mice (BALB/c or C3H/HeN) or method of infection, demonstrate the importance of decorin in the pathogenesis of LD.

Animals↗
PubMed2001

Criminal harassment by patients with mental disorders.

OBJECTIVE: To assess whether there is a subgroup of persons with mental disorders who engage in criminal harassment and to determine whether substance abuse is a cofactor in this behaviour. METHOD: A cross-sectional casenote study was used to examine incidents of harassment by patients prior to admission to acute and forensic wards (n = 106) at a provincial psychiatric hospital. RESULTS: Of 106 patients, 8 (7.5%) were found to have engaged in behaviour defined as criminal harassment prior to admission. Only 1 was charged under Section 264 of the Criminal Code. Alcohol was a cofactor in only 1 case. CONCLUSIONS: The number of persons with a mental disorder who engage in criminal harassment prior to admission is relatively small. The behaviour is not usually identified at any stage of the admission as criminal harassment. Although substance-abuse problems were prevalent, substance use was not a concomitant risk factor for behaviour defined as criminal harassment.

Adult↗
PubMed2001

Preparation by recombinant human thyrotropin or thyroid hormone withdrawal are comparable for the detection of residual differentiated thyroid carcinoma.

Clinical recurrences of differentiated thyroid carcinoma occur in 20% of patients after thyroid surgery. We performed a retrospective analysis of a cohort of patients undergoing routine follow-up testing to detect recurrent thyroid carcinoma over a 2-yr period. One group was prepared for testing by thyroid hormone withdrawal (THW), and the other group remained on thyroid hormone and received injections of recombinant human TSH (rhTSH) before diagnostic whole-body radioiodine scanning (DxWBS). We hypothesized that no differences in the ability to detect residual disease would exist between these 2 groups. Two hundred and eighty-nine patients were examined by both DxWBS and by measurement of the serum thyroglobulin (Tg) response to elevated TSH levels. THW was used for 161 patients, and rhTSH preparation was used for 128 patients. Based on all available testing results, we categorized patients as having metastatic disease, thyroid bed uptake only, or no evidence of disease. We examined the sensitivity, specificity, positive and negative predictive values of the DxWBS, and the stimulated Tg after preparation by THW or rhTSH. Patients with thyroid bed were not considered in accuracy testing. The sensitivity and specificity of the 2 tests were comparable between groups. No significant differences were present in the positive or negative predictive values between groups. The highest negative predictive value (97%) was in patients who had both a negative DxWBS and low stimulated Tg levels after rhTSH. In summary, we were unable to demonstrate a difference in the diagnostic accuracy of DxWBS and/or Tg between patients prepared by either THW or rhTSH. We conclude that preparing patients by rhTSH is diagnostically equivalent to preparing them by THW.

Adult↗
PubMed2001

Physiological rationale for responsiveness of mouse embryonic stem cells to gp130 cytokines.

Embryonic stem cells are established directly from the pluripotent epiblast of the preimplantation mouse embryo. Their derivation and propagation are dependent upon cytokine-stimulated activation of gp130 signal transduction. Embryonic stem cells maintain a close resemblance to epiblast in developmental potency and gene expression profile. The presumption of equivalence between embryonic stem cells and epiblast is challenged, however, by the finding that early embryogenesis can proceed in the absence of gp130. To explore this issue further, we have examined the capacity of gp130 mutant embryos to accommodate perturbation of normal developmental progression. Mouse embryos arrest at the late blastocyst stage when implantation is prevented. This process of diapause occurs naturally in lactating females or can be induced experimentally by removal of the ovaries. We report that gp130(-/-) embryos survive unimplanted in the uterus after ovariectomy but, in contrast to wild-type or heterozygous embryos, are subsequently unable to resume development. Inner cell masses explanted from gp130(-/-) delayed blastocysts produce only parietal endoderm, a derivative of the hypoblast. Intact mutant embryos show an absence of epiblast cells, and Hoechst staining and TUNEL analysis reveal a preceding increased incidence of cell death. These findings establish that gp130 signalling is essential for the prolonged maintenance of epiblast in vivo, which is commonly required of mouse embryos in the wild. We propose that the responsiveness of embryonic stem cells to gp130 signalling has its origin in this adaptive physiological function.

Animals↗
PubMed2001

Factors associated with self-disclosure of HIV serostatus to significant others.

OBJECTIVES: To examine rates and patterns of self-disclosure of HIV serostatus amongst individuals attending an out-patient HIV clinic in East London. DESIGN: A cross-sectional survey design was used. METHODS: A volunteer sample of 95 out-patient HIV clinic attendees completed a self-report questionnaire examining patterns of disclosure to self-identified significant others, reasons for disclosure and non-disclosure, satisfaction with social support (SSQ6), quality of life (MOS-30) and anxiety and depression (HADS). Self-disclosure was examined in relation to cultural background, gender, satisfaction with social support, and medical and psychological variables. RESULTS: Seventy-nine men and 16 women reported a mean disclosure rate of 68% to self-identified significant others. Five individuals had not disclosed their HIV status to anyone; 91% of individuals had informed their partner. Friends were more frequently informed (79%) than family (53%). Ethnicity (p <.001) and length of time since testing HIV seropositive (p <.05) emerged as significant predictors of disclosure. Global satisfaction with social support was negatively correlated with depression but was not associated with the total rate of HIV disclosure. Frequently reported reasons for non-disclosure included wanting to protect others from distress and fear of discrimination. CONCLUSIONS: Self-disclosure of HIV serostatus rates was highest for partners, followed by friends, and lowest for family members. Patterns of disclosure of HIV serostatus varied in relation to ethnicity. Fifteen years into the HIV epidemic, social stigma continues to contribute towards non-disclosure of diagnosis.

Journal Article↗
PubMed2001

Relationship between sexual partners influences rates and correlates of condom use.

A common finding in studies of heterosexual young adults is that condom use is more likely with casual partners than with regular partners. However, few studies have examined whether correlates of condom use differ with different partners. In this study, 103 heterosexual men and women completed a condom use diary for a period of up to 6 months. Condom use during sexual encounters with regular partners was mainly determined by established patterns of behavior. In contrast, condom use with casual partners was determined by the interaction between the sexual partners during the encounter, and was not influenced by the attitudes and beliefs of the individual. These differences have implications for interventions. They suggest that condom use with casual partners may be increased by furnishing young adults with skills and confidence for negotiating condom use. For young adults in regular relationships, we must ensure that routine patterns of condom use are appropriate for the levels of risk to which the partners are exposed.

Adolescent↗
PubMed2001

The effects of rhBMP-2 on human osteosarcoma cells and human gingival fibroblasts in vitro.

Certain cells of the periodontium are necessary for the regeneration of tissues that are destroyed as a result of periodontal disease. There has been debate regarding which cells are the primary participants in periodontal regeneration. It is a well-known fact that osteoblasts are essential in new bone formation, but controversy surrounds the role that gingival fibroblasts may play in the regeneration of the hard tissues of the periodontium. If gingival fibroblasts could contribute to the regeneration of these tissues, they might provide an additional source of progenitor cells. The bone morphogenetic proteins are potent stimulators of cell differentiation and have been shown to induce new bone formation in many experimental models. This project investigated the ability of recombinant human bone morphogenetic protein-2 (rhBMP-2) to (1) enhance the production of markers of osteoblastlike cells (osteocalcin and mineralization in culture) in human osteosarcoma cells (MG63) and to (2) induce the expression of an osteoblast phenotype in cultured human gingival fibroblasts (HGFs). MG63 cells and pooled HGFs were exposed to varying concentrations of rhBMP-2 for 24, 48, and 72 hours after 9 days in culture, and osteocalcin levels were measured by enzyme immunosorbent assay in the cell supernatants. In addition, the cells were exposed to rhBMP-2 for 72 hours after 18 days in culture, and mineralization was determined by the Von Kossa stain. The rhBMP-2 had an inhibitory effect on both osteocalcin production and mineralization (p < 0.05) in MG63 cells compared with untreated controls. In addition, increasing doses of rhBMP-2 inhibited both osteocalcin and mineralization in HGF cells. These results suggest that HGFs can express an osteoblastic phenotype when exposed to rhBMP-2; however, rhBMP-2 has inhibitory effects at higher rhBMP-2 doses in both cell types and may, in fact, be inhibitory to MG63 cells.

Bone Morphogenetic Protein 2↗
PubMed2001

Young people's contraception and sexual health: report of a local needs assessment in Staveley, North Derbyshire.

This project assessed the contraception and sexual health needs of people aged under 25 years in the small town of Staveley, UK, and sought to determine how the community family planning service could best meet these needs. One hundred and seventeen young people and 17 local professionals took part. The preferred ideal was found to be a holistic youth service based in an accessible, non-clinic setting. Clinic-based services should be more user-friendly, and various ways to achieve this were suggested. Both clients and professionals need greater awareness of all local services.

Adolescent↗