Search PubMed⌕ Search

Biomedical subjects

S Smith

Publications and source records attributed to S Smith.

At least 37 records · Page 2Linked to original sources
PubMed2002

A comparison of the plaque-inhibitory properties of stannous fluoride and low-concentration chlorhexidine mouthrinses.

BACKGROUND: Plaque inhibition by chlorhexidine (CHX) rinses is dose related with a relatively flat dose-response curve above 5-6 mg twice daily. Low dose regimens could therefore reduce local side effects but maintain reasonable efficacy. AIMS: To compare the plaque inhibitory properties of two low-dose CHX rinse products with more conventional levels delivered from proprietary rinses. A secondary outcome was a comparison with a stannous fluoride/amine fluoride (SFAF) rinse product. METHODS: The study was a five-treatments, negative controlled, randomised, single blind crossover design balanced for residual effects, involving 20 healthy subjects in a 24-h plaque re-growth model. On day 1 of each study period, subjects were rendered plaque free, suspended tooth cleaning and followed the appropriate rinse regimen. On day 2, subjects were scored for plaque by index and area. The rinse codes and rinsing regimens were: (A) 15 mg CHX 2 x daily for 30 s (0.1% CHX), (B) 9 mg CHX 2 x daily for 60 s (0.06% CHX), (C) 10 ml SFAF rinse 1 x daily for 30 s, (D) 15 ml placebo 2 x daily for 60 s, and (E) 6 mg CHX 2 x daily for 30 s (0.06% CHX). RESULTS: Average mouth plaque indices and areas were highly significantly different between rinsing regimens. All test rinses were significantly more effective than the placebo rinse. There was a mean dose-response pattern for the CHX rinses, but there were no statistically significant differences between any of the test rinses. CONCLUSIONS: Lower doses of chlorhexidine in rinses can be used to exert plaque inhibition comparable with products used at higher doses and equivalent to benchmark products such as the SFAF rinse. However, the availability of chlorhexidine from formulations has to be considered as in part explaining the results.

Adult↗
PubMed2002

A comparison of oral transmucosal fentanyl and oral midazolam for premedication in children.

Oral transmucosal fentanyl citrate (OTF) was compared with midazolam as a premedicant in a prospective, randomised, placebo-controlled, double-blind trial. Eighty children (ASA grade 1 or 2, aged 3-9 years) who presented for tonsillectomy were randomly allocated to receive either 2.5 ml OTF (15-20 microg.kg(-1)) in a lollipop format and 0.5 ml.kg(-1) placebo syrup, or midazolam syrup (0.5 mg.kg(-1)) and a placebo lollipop (2.5 ml). The acceptability of sedation, anxiety and compliance with anaesthetic induction were assessed. The children were given an 'emergence' score for their recovery. Analgesia requirements, the incidence of vomiting, itching and any behavioural changes were assessed for 6 h postoperatively. Oral transmucosal fentanyl citrate was as effective as midazolam in aiding compliance with anaesthesia, but is significantly better in its appeal to children (p < 0.001) and emergence (p < 0.001) characteristics. In conclusion, OTF may be particularly useful as a premedicant in paediatric practice.

Administration, Oral↗
PubMed2002

Human T cell responses to peptides of the Mycobacterium leprae 45-kD serine-rich antigen.

In order to identify T cell epitopes within the Mycobacterium leprae 45-kD serine-rich antigen, we analysed responses to overlapping 17-mer peptides encompassing the whole antigen in non-exposed UK controls, Pakistani leprosy patients and tuberculosis patients in both the United Kingdom and Pakistan. This antigen has been described as M. leprae-specific, although it has a hypothetical homologue in M. tuberculosis. Human peripheral blood mononuclear cells were stimulated with peptide for 5 days and IFN-gamma measured in supernatants by ELISA. Some peptides were recognized more frequently by T cells from tuberculoid leprosy patients than those from UK controls, suggesting that such T cell epitopes might have diagnostic potential, while other peptides induced greater responses among UK control subjects. Short-term cell lines confirmed that these assays detected specific T cell recognition of these peptides. However, many tuberculosis patients also recognized these potentially specific peptides suggesting that there could be a true homologue present in M. tuberculosis.

Amino Acid Sequence↗
PubMed2002

Growth factor rescue of cytokine mediated trophoblast apoptosis.

INTRODUCTION: Apoptosis can be induced in cytotrophoblasts and syncytiotrophoblast in culture by a combination of TNF-alpha and IFN-gamma (Yui et al., 1994a; Garcia-Lloret et al., 1996). This apoptotic action of TNF-alpha and IFN-gamma can be inhibited/'rescued' by EGF (Garcia-Lloret et al., 1996). Additional 'survival' factors have been sought which might protect cells against apoptosis induced by TNF-alpha/IFN-gamma. The survival factors investigated were bFGF, IGF-1, PDGF-AA, VEGF and PLGF. These cytokines were chosen specifically because in common with EGF, the receptors for these molecules are all direct protein tyrosine kinases. MATERIALS AND METHODS: All the experiments were carried out using a standard cell culture protocol (Yui et al., 1994a, b; Garcia-Lloret et al., 1996). Apoptosis was induced using TNF-alpha/IFN-gamma, and rescue was attempted using the various cytokines. Apoptosis was identified using the TUNEL technique and quantified by counting 3000 cells in each experimental well. RESULTS: As in previous studies EGF produced a complete inhibition of the apoptotic action of TNF-alpha/IFN-gamma. bFGF, IGF-1, and PDGF-AA produced a partial but significant inhibition of the apoptotic action of TNF-alpha/IFN-gamma. VEGF and PLGF in these experiments had no protective effects against TNF-alpha/IFN-gamma induced apoptosis. DISCUSSION: Previous studies relating to EGF have been confirmed. bFGF, IGF-1, and PDGF have all been shown to provide partial protection against TNF-alpha/IFN-gamma induced apoptosis. VEGF and PLGF did not protect against apoptosis, and the mechanisms of action remain unclear.

Apoptosis↗
PubMed2002

HLA-DR 15 is associated with female sex and younger age at diagnosis in multiple sclerosis.

BACKGROUND: The association between multiple sclerosis and class II alleles of the major histocompatibility complex, in particular the DRB1*1501-DQB1*0602 haplotype, is well established but their role in determining specific features of this clinically heterogeneous disease is unknown as few studies involving large sample sizes have been performed. METHODS: 729 patients with multiple sclerosis were typed for the HLA DR15 phenotype. All patients underwent clinical assessment and a detailed evaluation of their clinical records was undertaken. RESULTS: The presence of DR15 was associated with younger age at diagnosis and female sex but there was no association with disease course (relapsing-remitting or secondary progressive v primary progressive type), disease outcome, specific clinical features (opticospinal v disseminated form), diagnostic certainty (clinically and laboratory supported definite v clinically probable multiple sclerosis), and paraclinical investigations including the presence of oligoclonal bands in the CSF or characteristic abnormalities on MRI imaging of the central nervous system. CONCLUSION: Even though DR15 carriers are more likely to be female and prone to an earlier disease onset, the results indicate that there is no association with other specific clinical outcomes or laboratory indices examined here. This suggests that DR15 exerts a susceptibility rather than disease modifying effect in multiple sclerosis.

Adolescent↗
PubMed2002

Do mental disorders matter? A study of absenteeism among care seeking Gulf War veterans with ill defined conditions and musculoskeletal disorders.

AIMS: To investigate the extent that common psychological conditions contribute to lost work among individuals with musculoskeletal and ill defined conditions. METHODS: Cross sectional health and work related survey evaluating Gulf War veterans seeking Department of Defense health care for Gulf War related health concerns. Ordered probit models were used to study whether a provider diagnosed musculoskeletal condition (ICD-9 codes 710-739) or "signs, symptoms, and ill defined conditions" (ICD-9 codes 780-799) have an effect on recent lost work over the previous 90 days in the presence of one or more psychological conditions (ICD-9 codes 290-320) after controlling for sociodemographic variables. RESULTS: Bivariate analyses revealed that musculoskeletal conditions, ill defined conditions, and psychological conditions were positively associated with lost work. Multivariate analyses showed an independent effect of both psychological conditions and musculoskeletal conditions. A significant interaction existed between psychological conditions and musculoskeletal conditions: the presence of a coexisting psychological condition considerably increased the likelihood that a musculoskeletal disorder resulted in lost work, or vice versa. CONCLUSIONS: Psychological conditions appear to be an important contributor to absenteeism among individuals with musculoskeletal and ill defined conditions. A limitation of the cross sectional design was the inability to sequence the onset of conditions.

Absenteeism↗
PubMed2002

mSprouty2 inhibits FGF10-activated MAP kinase by differentially binding to upstream target proteins.

Murine Sprouty2 (mSpry2) is a conserved ortholog of Drosophila Sprouty, a gene that inhibits several tyrosine kinase receptor pathways, resulting in net reduction of mitogen-activated protein (MAP) kinase activation. However, the precise mechanism mediating mSpry2 function as a negative regulator in tyrosine kinase growth factor pathways that regulate diverse biological functions remains incompletely characterized. Fibroblast growth factor 10 (FGF10) is a key positive regulator of lung branching morphogenesis and induces epithelial expression of mSpry2 adjacent to mesenchymal sites of FGF10. Herein, we demonstrate that FGF10 stimulation of mouse lung epithelial cells (MLE15) overexpressing mSpry2 results in both mSpry2 tyrosine phosphorylation and differential binding of mSpry2 to several key upstream target proteins in the MAP kinase-activating pathway. Thus FGF receptor (FGFR) activation results in increased association of mSpry2 with growth factor receptor-binding protein 2, suc-1-associated nuerotrophic factor target 2, and Raf but decreased binding to protein tyrosine phosphatase 2 and GTPase-activating protein 1, resulting in a net reduction of MAP kinase activation. mSpry2 also spatially translocates to the plasma membrane and intracellular membrane structures in response to FGF10 stimulation. Our data demonstrate novel intracellular mechanisms mediating mSpry2 function as a negative regulator of uncontrolled FGF-induced MAP kinase signaling.

Amino Acid Sequence↗
PubMed2002

Cerebellar responses during anticipation of noxious stimuli in subjects recovered from depression. Functional magnetic resonance imaging study.

BACKGROUND: Subjects recovered from depression have a substantial risk for recurrence of depression, suggesting persistent abnormalities in brain activity. AIMS: To test whether women recovered from depression show abnormal brain activity in functional magnetic resonance imaging (fMRI) during a conditioning paradigm with a noxious pain stimulus. METHOD: Ten unmedicated women who had recovered from major depression and eight healthy control women each received either noxious hot or non-noxious warm stimuli, the onset of which was signalled by a specific coloured light during 3-tesla echo planar imaging-based fMRI. RESULTS: Similar patterns of brain activation were found during painful stimulation for both patients and healthy controls. However, relative to healthy controls, subjects recovered from depression showed a reduced response in the cerebellum during anticipation of the noxious stimulus compared with anticipation of the non-noxious stimulus. CONCLUSIONS: Our data suggest that abnormal cerebellar function could be a marker of vulnerability to recurrent depression. This could provide a new target for therapeutic interventions.

Adult↗
PubMed2002

Abnormal bone architecture and biomechanical properties with near-lifetime treatment of rats with PTH.

Skeletal effects are described for near-lifetime treatment of young, female rats with recombinant human PTH (1-34) (PTH). Rats (5-8 wk of age) were administered 0, 5, 30, or 75 microg/kg x d sc PTH for up to 2 yr, as part of an oncogenicity evaluation, which is required by regulatory agencies for potential chronic therapies. Proliferative lesions were observed in the skeleton as described in Vahle et al. (1 ); in this paper, we describe the quantitative bone data for this study. In the appendicular skeleton, PTH stimulated trabecular and endocortical mineral apposition to the near exclusion of marrow spaces at 5 microg/kg, with some periosteal apposition at 30 microg/kg, followed by considerable periosteal apposition and altered geometry at 75 microg/kg. Increased bone mass was observed for all treatment groups that substantially exceeded normal levels attained by vehicle controls and exceeded skeletal efficacy reported previously for similar doses in shorter-term studies. Dose-dependent increases in osteocalcin levels and a linear increase in wet weight of femora were observed for the entire treatment duration, suggesting nearly continuous PTH stimulation of osteoblasts and skeletal growth throughout life. Histology showed many osteocytes and prominent osteoblasts, but a conspicuous absence of osteoclasts. Morphometry showed a lack of distinction between trabecular and cortical bone. Biomechanics of vehicle controls showed that optimal mechanical integrity for the normal skeleton is observed at about 11 months of age. PTH greatly strengthened and stiffened vertebra and femora; however, the midshaft showed reduced toughness and increased brittleness with treatment, which was not the case for vertebra. Related studies of 6 and 9 months duration showed that the optimal duration for PTH skeletal efficacy was about 6 months in rats, based on toughness, strength, ultimate displacement, and architecture, especially for cortical bone. Therefore, treatment duration is an under appreciated aspect of PTH pharmacology; and PTH skeletal effects are a complex function of dose and duration. Comparative analyses showed that short-term treatment (6 months or less) is more advantageous than near-lifetime treatment, because PTH stimulates skeletal growth throughout life, resulting in abnormal architecture and untoward biomechanical properties in rats.

Absorptiometry, Photon↗
PubMed2002

Mutational status of overexpressed p16 in head and neck cancer: evidence for germline mutation of p16/p14ARF.

Inactivation of the p16 tumor suppressor gene is a common phenomenon in squamous cell carcinoma of the head and neck (SCCHN). Less commonly described is the observation of p16 overexpression in SCCHN. Since overexpression of p16 is a potent predictor of outcome in other cancers, we were interested in determining the level of expression of p16 in our SCCHN specimens as a prerequisite to later prognostic studies. We were also interested in determining the mutational status of p16 in these tumors, in order to determine whether the combination of overexpression and gene alteration may predict a different clinical outcome from overexpression alone. A total of 84 specimens of SCCHN were selected for study. These specimens were obtained from all major sites within the oral cavity, oropharynx, pharynx and larynx. The level of expression of p16 in SCCHN specimens was measured by semi-quantitative RT-PCR. In 35 cases, RNA was also isolated from matched normal tissue obtained from a negative tumor margin. In the other 49 cases, the expression level was compared with the level of expression measured in pooled normal RNA obtained from 10 specimens of normal epithelial tissue. Overexpression of p16 was documented when the level of expression in the tumor specimen was 2-fold or greater above the level of expression found in normal tissue. A total of 46 specimens demonstrated overexpression of p16 (55%). All specimens demonstrating overexpression were then subject to sequence analysis. Thirty specimens (65%) showed p16-specific gene alterations, ranging from intragenic deletions to single point mutations, and 15 of these cases concomitantly affect p14ARF. A single specimen demonstrated a silent point mutation within the p16 reading frame. This mutation produces a stop codon at residue 85 in the context of the p14ARF reading frame, predicting premature termination of p14ARF within a previously determined nucleolar localization signal. This observation suggests that in some cases at least, p14ARF may be a selective target for alteration, independently of p16. Analysis of a normal tissue specimen obtained from a negative tumor margin, and a blood sample obtained approximately five years after surgery indicate that this p14ARF-specific alteration may represent a germline mutation.

Carcinoma, Squamous Cell↗
PubMed2001

Allantoin formation and urate and glutathione exchange in human muscle during submaximal exercise.

Seven males performed two exhaustive cycling bouts (EX1 and EX2) at a work-rate of 90% of maximal oxygen uptake, separated by 60 min. During EX1 there was a significant accumulation of urate (from 0.16 +/- 0.02 to 0.27 +/- 0.03 micromol/kg d.w.) and allantoin (from 0.39 +/- 0.05 to 0.69 +/- 0.14 micromol/kg d.w.) in the muscle. An uptake of urate was observed in early recovery from EX1 (0-9 min: 486 +/- 136 micromol; p <.05). There was no exchange of total glutathione or cysteine over the muscle either during or after exercise, and muscle and plasma total glutathione remained unaltered (p <.05). The glycogen levels were lowered by 40% at the onset of EX2, yet the level of oxidative stress in EX1 and EX2 was similar as evidenced by a similar increase in muscle allantoin in both exercise bouts. The data suggest that urate is utilized as antioxidant in human skeletal muscle and that reactive oxygen species are formed in muscle during intense submaximal exercise. No net exchange of glutathione appears to occur over the muscle either at rest, during exercise or in recovery. Moreover, when an exhaustive exercise bout is repeated with lowered glycogen levels, the level of oxidative stress is not different than that of the first bout.

Adenosine Triphosphate↗
PubMed2001

The care of HIV-infected adults in rural areas of the United States.

OBJECTIVE: This study describes the population of HIV-infected adults receiving care in rural areas of the United States and compares HIV care received in rural and urban areas. METHODS: Interviews were conducted with a nationally representative sample of 367 HIV-infected adults receiving health care in rural areas and 2806 HIV-infected adults receiving health care in urban areas of the contiguous United States. RESULTS: We estimate that 4800 HIV-infected persons received medical care in rural areas during the first half of 1996. Patients in rural HIV care were more likely than patients in urban HIV care to receive care from providers seeing few (<10) HIV-infected patients (38% vs. 3%; p <.001). Rural care patients were less likely than urban care patients to have taken highly active antiretroviral agents (57% vs. 73%; p <.001) or Pneumocystis carinii pneumonia prophylactic medication when indicated (60% vs. 75%; p =.006). CONCLUSIONS: Few American adults received HIV care in rural areas of the United States. Our findings suggest ongoing disparities between urban and rural areas in access to high-quality HIV care.

Adult↗
PubMed2001

Trithorax and dCBP acting in a complex to maintain expression of a homeotic gene.

Trithorax (Trx) is a member of the trithorax group (trxG) of epigenetic regulators, which is required to maintain active states of Hox gene expression during development. We have purified from Drosophila embryos a trithorax acetylation complex (TAC1) that contains Trx, dCBP, and Sbf1. Like CBP, TAC1 acetylates core histones in nucleosomes, suggesting that this activity may be important for epigenetic maintenance of gene activity. dCBP and Sbf1 associate with specific sites on salivary gland polytene chromosomes, colocalizing with many Trx binding sites. One of these is the site of the Hox gene Ultrabithorax (Ubx). Mutations in either trx or the gene encoding dCBP reduce expression of the endogenous Ubx gene as well as of transgenes driven by the bxd regulatory region of Ubx. Thus Trx, dCBP, and Sbf1 are closely linked, physically and functionally, in the maintenance of Hox gene expression.

Acetylation↗
PubMed2001

Argon plasma coagulation for rectal bleeding after prostate brachytherapy.

PURPOSE: To better define the efficacy and safety of argon plasma coagulation (APC), specifically for brachytherapy-related proctitis, we reviewed the clinical course of 7 patients treated for persistent rectal bleeding. Approximately 2-10% of prostate cancer patients treated with 125I or 103Pd brachytherapy will develop radiation proctitis. The optimum treatment for patients with persistent bleeding is unclear from the paucity of available data. Prior reports lack specific dosimetric information, and patients with widely divergent forms of radiation were grouped together in the analyses. METHODS AND MATERIALS: Seven patients were treated with APC at the Veterans Affairs Puget Sound Health Care System and the University of Washington from 1997 to 1999 for persistent rectal bleeding due to prostate brachytherapy-related proctitis. Four patients received supplemental external beam radiation, delivered by a four-field technique. A single gastroenterologist at the Veterans Affairs Puget Sound Health Care System treated 6 of the 7 patients. If the degree of proctitis was limited, all sites of active bleeding were coagulated in symptomatic patients. An argon plasma coagulator electrosurgical system was used to administer treatments every 4-8 weeks as needed. The argon gas flow was set at 1.6 L/min, with an electrical power setting of 40-45 W. RESULTS: The rectal V100 (the total rectal volume, including the lumen, receiving the prescription dose or greater) for the 7 patients ranged from 0.13 to 4.61 cc. Rectal bleeding was first noticed 3-18 months after implantation. APC (range 1-3 sessions) was performed 9-22 months after implantation. Five patients had complete resolution of their bleeding, usually within days of completing APC. Two patients had only partial relief from bleeding, but declined additional APC therapy. No patient developed clinically evident progressive rectal wall abnormalities after APC, (post-APC follow-up range 4-13 months). CONCLUSIONS: Most patients benefited from APC, and no cases of clinically evident progressive tissue destruction were noted. Although APC appears to be efficacious and safe in the setting of the rectal doses described here, caution is in order when contemplating APC for brachytherapy patients.

Argon↗