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Biomedical subjects

S Smith

Publications and source records attributed to S Smith.

At least 163 records · Page 9Linked to original sources
PubMed2001

Gelatine-resorcine-formol glue as a sealant of ePTFE patch suture lines.

BACKGROUND: ePTFE patch reconstruction has superior flow characteristics in preventing early thrombus formation during carotid endarterectomy. However prolonged bleeding at the suture line of the patch reconstruction is a problem. The aim of this study was to investigate whether the application of gelatine-resorcine-formol (GRF) glue at the suture line can improve local haemostasis. METHODS: A prospective randomised trial of 40 consecutive patients undergoing carotid endarterectomy was undertaken. Patients were randomised to receive GRF glue as a topical haemostatic agent or to act as controls. Statistical analysis was performed using the Mann-Whitney test. RESULTS: Although the patch size was significantly smaller in the control group (3.0 cm2 vs 4.3 cm2, p<0.001), local haemostasis was achieved in half the time when the glue was used (11 min vs 22, p<0.004). In the follow-up period ranging from 12 to 24 months, there have been no adverse effects related to the glue. Two patients died during the follow-up period. These deaths were neither related to the patch nor to the glue. CONCLUSIONS: This study has shown that GRF glue is an effective sealant of ePTFE patch suture line. GRF glue does not compromise the patch's characteristics.

Aged↗
PubMed2001

Infants, the dead donor rule, and anencephalic organ donation: should the rules be changed?

When parents learn that their baby will be anencephalic, tragic choices must be made concerning how aggressively the infant should be treated. The parents' acceptance of the seriousness of the condition is often accompanied by their desire to donate the child's organs as a way of making an anencephalic's brief existence seem meaningful. Current U.S. law precludes parents from choosing organ donation, however, unless the child meets the "whole brain death" definition. Critics of restrictive organ donation policies founded on the whole brain death definition have responded in two ways. Some have proposed revisions that would broaden this definition of death. Others have appealed to interpretations that allow organ procurement from non-heart-beating donors and argue that this interpretation should be applied to anencephalics. We will consider both responses to policies restricting anencephalic organ donation by addressing international legal perspectives on whether a "duty to rescue" exists in this context and whether the need for increased organ donation is so urgent that it is justified to adopt less stringent guidelines overall. Finally, we will focus on the issue of the limits of parental decision making on behalf of anencephalics.

Anencephaly↗
PubMed2001

The North Dublin Diabetes Shared Care (DiSC) Project: a profile of current diabetes care in Ireland.

The DiSC Project aims to assess the feasibility, effectiveness and costs of diabetes shared care in Ireland. Baseline results provide a profile of diabetes care in Ireland. Thirty general practices are participating in this randomised controlled trial. Outcomes include biophysical and psychosocial measures. The majority of patients agreed to participate in diabetes shared care. Data was collected from 183 patients with type 2 diabetes. The mean age of the patients is 65 years, 56% are male and 63% are GMS eligible. The mean HBA1c was 6.8% though 21% of patients had a HBA1c>8%. The majority of patients had a blood pressure, total cholesterol and body mass index above recommended guidelines. Only half the patients are attending a dietician or a chiropodist. The majority of patients have good glycaemic control but poor blood pressure and cholesterol control. The full trial results will determine if a shared care approach can improve clinical and psychosocial outcomes for patients.

Adult↗
PubMed2000

T cell expression cloning of a Mycobacterium tuberculosis gene encoding a protective antigen associated with the early control of infection.

Infection of C57BL/6 mice with Mycobacterium tuberculosis results in the development of a progressive disease during the first 2 wk after challenge. Thereafter, the disease is controlled by the emergence of protective T cells. We have used this infection model in conjunction with direct T cell expression cloning to identify Ags involved with the early control of the disease. A protective M. tuberculosis-specific CD4 T cell line derived from mice at 3 wk postchallenge was used to directly screen an M. tuberculosis genomic expression library. This screen resulted in the identification of a genomic clone comprising two putative adjacent genes with predicted open reading frames of 10 and 41 kDa, MTB10 and MTB41, respectively (the products of Rv0916c and Rv0915c, respectively, in the TubercuList H37Rv database). MTB10 and MTB41 belong to the PE and PPE family of proteins recently identified to comprise 10% of the M. tuberculosis genome. Evaluation of the recombinant proteins revealed that MTB41, but not MTB10, is the Ag recognized by the cell line and by M. tuberculosis-sensitized human PBMC. Moreover, C57BL/6 mice immunized with MTB41 DNA developed both CD4- (predominantly Th1) and CD8-specific T cell responses to rMTB41 protein. More importantly, immunization of C57BL/6 mice with MTB41 DNA induced protection against infection with M. tuberculosis comparable to that induced by bacillus Calmette-Guérin. Thus, the use of a proven protective T cell line in conjunction with the T cell expression cloning approach resulted in the identification of a candidate Ag for a subunit vaccine against tuberculosis.

Animals↗
PubMed2000

A randomised, double-blind, controlled trial of the immunogenicity and tolerability of a meningococcal group C conjugate vaccine in young British infants.

A double-blind, randomised, controlled trial was conducted in 248 British infants to assess the immunogenicity and tolerability of three doses of a meningococcal group C/CRM (197) conjugate vaccine (Lederle Laboratories, USA) given at 2, 3 and 4 months. Control children received three doses of Hepatitis B vaccine (Engerix B(R); SmithKline Beecham). At 5 months of age, 100% of children receiving the conjugate vaccine had specific immunoglobulin G concentrations >2.0 microg/ml (n=116) compared with only 4% of control children (n=121). Those receiving the conjugate also had 2.5- and 1.6-fold higher geometric mean concentrations of PRP and diphtheria antibodies, respectively. The vaccine was well tolerated.

Antibodies, Bacterial↗
PubMed2000

A novel nitrate ester reverses the cognitive impairment caused by scopolamine in the Morris water maze.

The objective of this study was to test the hypothesis that activation of soluble guanylyl cyclase and increased cGMP formation in the brain would improve task acquisition in cognitively impaired animals. We evaluated the effects of a novel nitrate ester, GT 715 (2,3-dinitrooxy-(2,3-bis-nitrooxypropyldisulfanyl)-propane), in scopolamine-induced impairment of task acquisition in the Morris water maze. GT 715 improved task acquisition in scopolamine-pretreated animals in a time- and dose-dependent manner, whereas the prototypical nitrate ester, glyceryl trinitrate (GTN), was ineffective. GT 715 also was more effective and more potent than GTN for activation of hippocampal guanylyl cyclase. The results of this study therefore suggest that stimulation of cerebral soluble guanylyl cyclase activity may be an effective strategy to improve learning and memory performance in individuals in whom cognitive abilities are impaired by injury, disease, or ageing.

Animals↗
PubMed2000

Tankyrase promotes telomere elongation in human cells.

Human telomeres are maintained by telomerase, a reverse transcriptase that adds telomeric repeats to chromosome ends [1,2]. In human tumors and immortalized cells, telomeres are often maintained at a constant length setting [3,4], indicating that telomerase-mediated telomere elongation is tightly regulated. Tankyrase, a telomeric poly(ADP-ribose) polymerase (PARP) [5], was identified through its interaction with TRF1 [6], a negative regulator of telomere extension by telomerase [7]. Tankyrase-mediated ADP-ribosylation inhibits binding of TRF1 to telomeric repeats in vitro [5], suggesting that tankyrase might regulate TRF1 and therefore control telomere dynamics in vivo. Here, we present evidence that tankyrase acts as a positive regulator of telomere elongation in vivo, apparently by inhibiting TRF1. Overexpression of tankyrase in the nucleus diminished the level of unmodified TRF1 in immunoblots and led to reduced immunofluorescence of TRF1 at interphase telomeres. Long-term overexpression of tankyrase in telomerase-positive human cells resulted in a gradual and progressive elongation of telomeres. A PARP-deficient form of tankyrase failed to affect TRF1 and did not alter telomere length dynamics, consistent with ADP-ribosylation of TRF1 as the main cause of altered telomere homeostasis. Our results indicate that tankyrase can induce telomere elongation in human cells. We propose that tankyrase-mediated ADP-ribosylation of TRF1 opens the telomeric complex, allowing access to telomerase.

DNA-Binding Proteins↗
PubMed2000

Quantification of polycyclic aromatic hydrocarbons in the NIST standard reference material (SRM1649A) urban dust using thermal desorption GC/MS

A thermal desorption GC/MS technique has been developed for the quantification of polycyclic aromatic hydrocarbons (PAHs) in airborne particulate matter using the NIST Standard Reference Material (SRM1649a) Urban Dust. The technique was developed using standard linearity tests in order to establish optimum sample weights and optimum desorption and chromatographic parameters. This direct analysis technique eliminates the use of solvents in the sample preparation (reducing volatile component losses) and also significantly reduces the sample preparation time (no extraction procedure). The technique has been shown to give linearity in terms of the overall TIC response as well as for a prominent series of n-alkanes (C20-C33) and 10 NIST priority PAHs, 8 of which have been quantified. The technique is reported to be uniquely sensitive (PAH concentrations 2-6 mg kg(-1)) and reproducible (MW = 178-228 SD < or =0.228 mg kg(-1), < or =7%; MW = 252 SD < or =0.922 mg kg(-1), < or =33%) over the range of sample weights (1-5 mg). Such sample weights illustrate that the technique can be equally applied to the analysis of airborne particulate samples collected over short time periods (24-48 h) using only commonly used low-volume collection devices.

Journal Article↗
PubMed2000

The human thioesterase II protein binds to a site on HIV-1 Nef critical for CD4 down-regulation.

A HIV-1 Nef affinity column was used to purify a 35-kDa Nef-interacting protein from T-cell lysates. The 35-kDa protein was identified by peptide microsequence analysis as the human thioesterase II (hTE) enzyme, an enzyme previously identified in a yeast two-hybrid screen as a potential Nef-interacting protein. Immunofluorescence studies showed that hTE localizes to peroxisomes and that coexpression of Nef and hTE leads to relocalization of Nef to peroxisomes. Interaction of Nef and hTE was abolished by point mutations in Nef at residues Asp(108), Leu(112), Phe(121), Pro(122), and Asp(123). All of these mutations also abrogated the ability of Nef to down-regulate CD4 from the surface of HIV-infected cells. Based on the x-ray and NMR structures of Nef, these residues define a surface on Nef critical for CD4 down-regulation. A subset of these mutations also affected the ability of Nef to down-regulate major histocompatibility complex class I. These results, taken together with previous studies, identify a region on Nef critical for most of its known functions. However, not all Nef alleles bind to hTE with high affinity, so the role of hTE during HIV infection remains uncertain.

Binding Sites↗
PubMed2000

A clinical prediction rule for nerve-function impairment in leprosy patients.

BACKGROUND: Nerve-function impairment (NFI) commonly occurs during or after chemotherapy in leprosy and is the key pathological process leading to disability and handicap. We describe the development of a simple clinical prediction rule for estimating the risk of NFI occurrence. METHODS: New leprosy cases who presented to a centre in Bangladesh were recruited and followed up for 2 years in a field setting. We used multivariable regression analysis by Cox's proportional hazards model to identify predictive variables for NFI. Discriminative ability was measured by a concordance statistic. Internal validity was assessed with bootstrap resampling techniques. FINDINGS: 2510 patients were followed up for 2 years, 166 developed NFI. A simple model was developed with leprosy group (either paucibacillary leprosy [PB] or multibacillary leprosy [MB]) and the presence of any nerve-function loss at registration as predictive variables. Patients with PB leprosy and no nerve-function loss had a 1.3% (95% CI 0.8-1.8%) risk of developing NFI within 2 years of registration; patients with PB leprosy and nerve-function loss, or patients with MB leprosy and no nerve-function loss had a 16.0% (12-20%) risk; and patients with MB leprosy with nerve-function loss had a 65% (56-73%) risk. INTERPRETATION: Our prediction rule can be used to plan surveillance of new leprosy patients. Patients at low risk of NFI may need no follow-up beyond their course of chemotherapy (6 months); patients with intermediate risk need a minimum of 1 year of surveillance; and patients with high risk should have at least 2 years of surveillance for new NFI. Current recommendations for surveillance of patients with leprosy (for the duration of chemotherapy only) exclude an important group of patients who are at risk of developing NFI after completion of treatment.

Adolescent↗
PubMed2000

Identification and analysis of two snail genes in the pufferfish (Fugu rubripes) and mapping of human SNA to 20q.

All members of the snail gene family are zinc-finger transcription factors expressed early in embryonic development and are involved in the formation of tissues such as mesoderm and presumptive neural crest. Here, we report the identification and structural organisation of two snail genes in the compact genome of the pufferfish Fugu rubripes, and examine the phylogenetic relationships between these and other members of the snail gene family. Both genes have a three exon, two intron structure similar to that previously reported for human SLUG. While human SLUG has been mapped to 8q (Cohen, M.E., Yin, M., Paznekas, W.A., Schertzer, M., Wood, S., Jabs, E.W., 1998. Human SLUG organisation, expression and chromosome map location on 8q. Genomics 51, 468-471), the human sna gene SNA, was previously unmapped. We have used sequence similarity to the Fugu genes to identify a human SNA EST and mapped this by radiation hybrid and physical mapping to the distal end of human 20q. This is likely to be the mapping location of the human sna gene (SNA).

Amino Acid Sequence↗
PubMed2000

Disposal and disease rates in 340 British dairy herds.

Data derived from 340 dairy herds, mainly in southern England, between April 1998 and March 1999, showed that the average total culling rate was 22.1 per cent, with 5.6 per cent for infertility, 3.6 per cent for mastitis, 1.7 per cent for lameness, 2.0 per cent for poor milk yield, 3.7 per cent for age and 5.5 per cent for miscellaneous reasons which included death. The average annual rate of assisted calvings was 8.7 per cent, of injury 0.9 per cent, digestive disease 1.3 per cent ketosis 0.4 per cent, hypomagnesaemia 0.7 per cent, hypocalcaemia 5.3 per cent, mastitis 36.6 per cent, and lameness 23.7 per cent. There was a significant association (P<0.001) between higher rates of mastitis in cows housed in straw yards as opposed to cubicles and also between higher rates of lameness in cows housed in cubicles as opposed to yards (P<0.015). However, there were farms with low rates of mastitis in cows kept in straw yards and low rates of lameness in cows kept in cubicles. Larger herds tended to have more problems with lameness and higher bulk milk somatic cell counts (BMSCC). There was a positive association between BMSCC and mastitis rate.

Animal Husbandry↗
PubMed2000

Systematic implementation of an advance directive program in nursing homes: a randomized controlled trial.

CONTEXT: Although advance directives are commonly used in the community, little is known about the effects of their systematic implementation. OBJECTIVES: To examine the effect of systematically implementing an advance directive in nursing homes on patient and family satisfaction with involvement in decision making and on health care costs. DESIGN: Randomized controlled trial conducted June 1, 1994, to August 31, 1998. SETTING AND PARTICIPANTS: A total of 1292 residents in 6 Ontario nursing homes with more than 100 residents each. INTERVENTION: The Let Me Decide advance directive program included educating staff in local hospitals and nursing homes, residents, and families about advance directives and offering competent residents or next-of-kin of mentally incompetent residents an advance directive that provided a range of health care choices for life-threatening illness, cardiac arrest, and nutrition. The 6 nursing homes were pair-matched on key characteristics, and 1 home per pair was randomized to take part in the program. Control nursing homes continued with prior policies concerning advance directives. MAIN OUTCOME MEASURES: Residents' and families' satisfaction with health care and health care services utilization over 18 months, compared between intervention and control nursing homes. RESULTS: Of 527 participating residents in intervention nursing homes, 49% of competent residents and 78% of families of incompetent residents completed advance directives. Satisfaction was not significantly different in intervention and control nursing homes. The mean difference (scale, 1-7) between intervention and control homes was -0.16 (95 % confidence interval [CI], -0.41 to 0.10) for competent residents and 0.07 (95% CI, -0.08 to 0.23) for families of incompetent residents. Intervention nursing homes reported fewer hospitalizations per resident (mean, 0.27 vs 0.48; P = .001) and less resource use (average total cost per patient, Can $3490 vs Can $5239; P = .01) than control nursing homes. Proportion of deaths in intervention (24%) and control (28%) nursing homes were similar (P = .20). CONCLUSION: Our data suggest that systematic implementation of a program to increase use of advance directives reduces health care services utilization without affecting satisfaction or mortality.

Advance Directives↗