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Biomedical subjects

C Smyth

Publications and source records attributed to C Smyth.

At least 19 recordsLinked to original sources

Blood splash from different diathermy instruments during tonsillectomy.

OBJECTIVE: To compare the potential risk of blood contamination of the surgeon's conjunctiva during tonsillectomy using disposable bipolar diathermy and reusable monopolar diathermy. DESIGN: A prospective, single-blind, randomized, controlled trial. METHODS: Elective tonsillectomy was performed using either disposable bipolar diathermy or reusable monopolar diathermy. The operating surgeon wore a ViewsafeTM protective eyeshield which was later examined under an operating microscope by a blinded observer and the number of blood spots counted. RESULTS: One hundred and sixty-eight patients were enrolled. The relative risk of conjunctival contamination of the surgeon using disposable bipolar diathermy was 2.8 times that with reusable monopolar diathermy (chi-squared test, p < 0.0005). A previous history of peritonsillar abscess and additional adenoidectomy were associated with increased blood splatter. CONCLUSION: The use of disposable bipolar diathermy for haemostasis during tonsillectomy poses a greater risk of conjunctival contamination for the surgeon than using reusable monopolar diathermy.

Adolescent↗

Rheology of aqueous carbon black dispersions.

The interaction of carbon black with an acrylic resin has been investigated by rheology. Two carbon blacks, with similar particle size and surface characteristics but quite different particle morphologies, have been examined. These are somewhat arbitrarily denoted as "spherical" and "fractal" as shown by small-angle neutron scattering (SANS) and ultrasonic spectroscopy studies. In the absence of polymer, stable aqueous dispersions could not be obtained. Stable dispersions could be obtained, however, upon addition of polymer to a level corresponding to a ratio of 50 mg of polymer per 13 m2 (+/- m2) of surface area (i.e., 15 wt% particles). These stable dispersions exhibit flow typical of concentrated dispersions-Newtonian behavior up to some apparent "yield" or critical value, above which pronounced shear thinning is observed. The critical stress increases with increasing polymer concentration. When a significant amount of nonadsorbed polymer is also present, a second Newtonian plateau is superimposed on the shear-thinning behavior. This feature is observed for both particle types but is more pronounced for the fractal particle. When there is little or no nonadsorbed polymer, the viscosity of the fractal particle dispersions is greater than the viscosity of the spherical particle dispersions. At low polymer concentrations, the dispersions are predominantly viscous at low shear stresses. The phase angle decreases significantly over a narrow shear stress range and the rheology tends to more elastic behavior. At higher shear stresses, the dependence on particle morphology is weak.

Journal Article↗

Refeeding syndrome: effective and safe treatment with Phosphates Polyfusor.

BACKGROUND: Severe hypophosphataemia associated with refeeding syndrome requires treatment with intravenous phosphate to prevent potentially life-threatening complications. However, evidence for replacement regimens is limited and current regimens are complex and replace phosphate inadequately. AIM: To assess the effectiveness and safety of 50 mmol intravenous phosphate infusion, given as a 'Phosphates Polyfusor', for the treatment of severe hypophosphataemia in refeeding syndrome. METHODS: Patients with refeeding syndrome and normal renal function received a Phosphates Polyfusor infusion for the treatment of severe hypophosphataemia (< 0.50 mmol/L). The outcome measures were serial serum phosphate, creatinine and calcium concentrations for 4 days following phosphate infusion and adverse events. RESULTS: Over 2 years, 30 patients were treated. Following treatment, 37% of cases had a normal serum phosphate concentration and 73% had a serum phosphate concentration of > 0.5 mmol/L within 24 h. Ten patients required more than one Phosphates Polyfusor infusion. Within 72 h, 93% of cases had achieved a serum phosphate concentration of > or = 0.50 mmol/L. No patient developed renal failure. Three episodes of transient mild hyperphosphataemia were recorded. Four patients developed mild hypocalcaemia. CONCLUSIONS: This is the largest published series of the use of intravenous phosphate for the treatment of severe hypophosphataemia (< 0.50 mmol/L), and is the most effective regimen described. All patients had refeeding syndrome and were managed on general wards.

Feeding Methods↗

Characteristics of Type 1 diabetes of over 50 years duration (the Golden Years Cohort).

BACKGROUND: Type 1 diabetes mellitus is associated with high levels of premature morbidity and mortality. Prolonged survival is possible, however, and some patients appear to be protected from the long-term complications of this condition. METHODS: Diabetes UK awards medals to patients who have had Type 1 diabetes for 50 years or more. By examining medal-holders, we have established the clinical and biochemical features of a group of 400 subjects (54% male) with Type 1 diabetes of long duration. RESULTS: Mean age of the subjects was 68.9 years and mean age-at-onset of diabetes 13.7 years. Features of long duration diabetes in this cohort include normal body mass (mean BMI 25.0 kg m-2), low insulin dose (mean 0.52 units kg-2) and greatly elevated HDL-cholesterol (mean 1.84 mmol/l). Mean HbA1c was 7.6% (normal range 3.8-5.0%) and no patient had a normal HbA1c at the time of venesection. As a group, they have long-lived parents and consume moderate amounts of alcohol. Medical contact has often been sporadic. A significant proportion (29%) were taking anti-hypertensive medication. Screening for micro- and macroalbuminuria was positive in 35.7%. CONCLUSIONS: Patients with long-duration (> 50 years) Type 1 diabetes are relatively protected from clinical diabetic nephropathy and large vessel disease; our data are consistent with protection possibly being genetically determined in part via elevated HDL-cholesterol levels. An abnormal urinary albumin/creatinine ratio is common in these patients, despite their low risk of significant renal deterioration; this may have implications for microalbuminuria screening programmes.

Aged↗

A prospective analysis of inpatient consultations to a gastroenterology service.

The provision of a formal consultation service for inpatients between subspecialists is little studied. We prospectively surveyed the pattern of inpatient consultations from hospital-based generalists and surgeons to the gastroenterology (GI) service for inpatients in a large urban teaching hospital over a 5 month period. There are two GI consultants/attendings and five GI registrars/fellows on the service. A formal consultation is made by the requesting team to the GI service using the hospital computer network. All referrals over a 5 month period were prospectively analysed. 242 consecutive inpatient referrals were sent to the GI service over 5 months. Average age was 56 years, 48.8% males. 32 consultants/attendings from other disciplines sent referrals. Most patients were seen within one working day. Urgent referrals were seen without delay. The commonest reasons for referral were abdominal pain (15.8%), percutaneous endoscopic gastrostomy (PEG) tube insertion (13.6%), diarrhoea (12.8%), abnormal liver blood tests (10%), nausea and vomiting (8.2%), anaemia (6.2%), and melaena (4.9%). Iatrogenic diseases accounted for 6.2% of consultations. Ongoing patient care was assumed by the GI team in 9.5% of referrals. 15.3% required a second consultation visit before discharge. 22.7% of referrals were followed in the GI outpatients' clinic after discharge. 51.2% underwent an endoscopic procedure. 13.6% of referrals were for PEG tube insertion. A quarter of these were considered unsuitable for immediate PEG tube insertion. Subspecialty consultation provides an expert opinion, encourages discussion and learning, and improves patient care. In our experience, the provision of specialist advice and reassurance often speeded up a patient's work-up and expedited discharge. However, evaluating referral patients and subsequently providing ongoing inpatient and outpatient care and provision of endoscopy for these referrals contributes significantly to the workload of the GI service.

Adolescent↗

Creating order out of chaos: models of GNP practice with hospitalized older adults.

It has been well documented that hospitalization of an older adult can trigger a cascade of events that negatively affect quality of life long after hospitalization. Three models of care directed by hospital-based geriatric nurse practitioners (GNPs) are described. The GNPs' roles include primary care provider, consultant, educator, researcher, and/or administrator. In one model, the GNP collaborated with a multi-disciplinary team to create a clinical pathway, the Functional Recovery Pathway. In the second model, the GNP and nurse manager addressed the issue of fall risk with an education program for the staff. As a result, the fall rate decreased 5.8%. In a third model, the GNP coordinated care of hospitalized nursing home residents in a "scatter bed" program. Working synergistically with a case management program, the length of stay for this group of patients decreased from a median of 12 days to 9 days in the first year to 6.8 days in the third year. All three models showed that the GNP facilitate change, improve resource utilization, and create innovative strategies to optimize care for hospitalized elders.

Accidental Falls↗

Pain measurement scales: a comparison of the visual analogue and faces rating scales in measuring pressure ulcer pain.

OBJECTIVE: Although different pain scales often have been used interchangeably, it is not known whether interchanging them is appropriate. The purpose of this report was twofold: to better understand the statistical properties of the Faces Rating Scale (FRS) so it can be used appropriately in clinical settings and to describe the mathematical relationship between the Visual Analogue Scale (VAS) and the FRS when they are used to quantify pressure ulcer pain in hospitalized elderly patients. DESIGN: Secondary data analyses were performed as part of a cross-sectional study. SETTING AND SUBJECTS: A quality assurance program was undertaken to evaluate pressure ulcer pain perceived by elderly hospitalized patients. All patients without aphasia participated. INSTRUMENTS: The VAS used was a 0 to 100 mm horizontal line demonstrated to have ratio scale properties with high validity and reproducibility, and the FRS used was 6 faces ordered horizontally from smiling to crying, labeled 0 to 5 beneath each face, respectively. METHODS: Nonlinear least squares regression with a Gauss-Newton iterative procedure was used. RESULTS: Among models with cubic, quadratic, and linear terms, only the quadratic term was significant (P <.05). With use of the equation derived, VAS = 3.33*(FRS)(2), the resulting reliability coefficient was r = 0.92. CONCLUSIONS: The nonlinear relationship indicated high reliability between VAS and FRS for pain assessment in populations with diminished verbal and abstract thinking abilities. For readers who would like to translate results from one scale to another, a quadratic equation is provided.

Adult↗

Gene transfer of the Bcl-2 gene confers cytoprotection to isolated adult porcine pancreatic islets exposed to xenoreactive antibodies and complement.

BACKGROUND: Exposing adult porcine pancreatic islets (PI) to xenoreactive natural antibodies (XNA) induces brisk inflammatory injury that involves activation of the complement system. Gene transfer of Bcl-2 has been shown to protect PI from apoptosis and necrosis in several models. In this study, we investigated the effect of Bcl-2 gene transfer on protection of PI from primate XNA and complement-mediated injury. METHODS: The PI were isolated from adult female sows. Only islet preparations that exhibited >90% viability and purity were used. Fresh rhesus monkey serum served as the XNA source. Gene transfer of Bcl-2 was achieved with an adenoviral vector (AdBcl-2) at 500 particle forming units (pfu)/cell. The Bcl-2 expression was confirmed by Western blot technique. Untransfected and transfected PI were incubated in 50% fresh complete serum (CS) or heat-inactivated (HI) rhesus serum for 24 hours. The PI viability was analyzed with acridine orange and ethidium bromide staining. Antibody and complement-mediated cytotoxicity were tested by intracellular lactate dehydrogenase (LDH) release. The PI function was assessed in vitro by static incubation studies and in vivo after intraportal transplantation in diabetic severe combined immunodeficiency (SCID) mice. RESULTS: The AdBcl-2 gene transfer resulted in Bcl-2 gene expression in >90% of PI cells. Following exposure to XNA, <15% of the untransfected cells were viable. Similar results were obtained in PI transfected with a similar recombinant adenovirus encoding the reporter gene E coli beta-galactosidase (AdLacZ), an irrelevant gene. A significant increase in LDH release was observed in control PI after exposure to CS compared with PI that overexpressed Bcl-2 (82.89% +/- 7.78% vs 34.31% +/- 5.4%, P <.005). Higher insulin release was observed in vitro in PI transfected with Bcl-2 compared with untransfected PI or islets transfected with AdLacZ (stimulation index of 0.9 +/- 0.31, 0.9 +/- 0.3 vs 2.67 +/- 0.4, respectively). Only PI treated with AdBcl-2 were able to achieve euglycemia after exposure to XNA and complement after transplantation. CONCLUSIONS: Transfer of the antiapoptotic and antinecrotic Bcl-2 gene into PI can reduce primate XNA and complement-mediated lysis. Cytoprotection of PI with Bcl-2 has potential to improve survival of PI xenotransplants.

Adenoviridae↗

A tripartite anoikis-like mechanism causes early isolated islet apoptosis.

BACKGROUND: This study examines the mechanisms of early isolated islet apoptosis (II-APO) and loss of functional islet mass. METHODS: Rhesus islets were isolated for transplantation, and an aliquot was used for in vitro molecular studies of II-APO. These studies used Western blotting to examine caspase activation and perinuclear envelope protein cleavage that are associated with II-APO and used immunofluorescence analysis of Annexin V and mitochondrial permeability index to examine spontaneous and tripartite anoikis-like (TRAIL) mechanism--induced II-APO. RESULTS: Caspase 6 was prominently activated in association with spontaneous II-APO, which occurred after overnight culture. In contrast, caspase 7, 8, and 9 were not activated. Cleavage of focal adhesion kinase and Lamin, substrates of caspase 6, was also evident in spontaneous II-APO. II-APO was exaggerated by the addition of the TRAIL mechanism. The TRAIL mechanism--induced II-APO was blocked by the caspase 6 inhibitor, VEID, and by the soluble fusion proteins, DR4 or DR5, which act as decoy receptors. In vivo studies in diabetic severe combined immunodeficiency disease mice showed that rhesus islets were cytoprotected by either ex vivo gene transfer of Bcl-2 or treatment of the isolated islet with VEID. CONCLUSIONS: These studies suggest 3 major mechanisms involved in II-APO: caspase 6 activation, a TRAIL-induced apoptosis pathway, and the mitochondrial-associated apoptosis pathway. Inhibition of these II-APO pathways may improve isolated islet survival and reduce functional islet mass loss, which compromises the stable reversal of diabetes.

Animals↗

Irritable bowel syndrome in general practice: prevalence, characteristics, and referral.

BACKGROUND AND AIMS: Little is known about the prevalence, symptoms, diagnosis, attitude, and referral to specialists of patients with irritable bowel syndrome (IBS) in general practice. This study aimed to determine these characteristics. METHODS: 3111 patients attending 36 general practitioners (GPs) at six varied locations in and near Bristol, UK, were screened to identify those with a gastrointestinal problem. These patients (n=255) and their doctors were given questionnaires. Six months later the case notes were examined to reach criteria based diagnoses of functional bowel disorders. RESULTS: Of 255 patients with a gastrointestinal complaint, 30% were judged to have IBS and 14% other functional disorders. Compared with 100 patients with an "organic" diagnoses, those with IBS were more often women and more often judged by their GP to be polysymptomatic and to have unexplained symptoms. The majority of patients with IBS (58%) were diagnosed as such by the GP; 22% had other functional diagnoses. Conversely, among 54 patients diagnosed as having IBS by the GPs, the criteria based diagnosis was indeed functional in 91%; only one patient had organic disease (proctitis). More patients with IBS than those with organic disease feared cancer. In most some fear remained after the visit to the doctor. On logistic regression analysis, predictors of referral to a specialist (29% referred) were denial of a role for stress, multiple tests, and frequent bowel movements. CONCLUSIONS: Half the patients with gut complaints seen by GPs have functional disorders. These are usually recognised, and few patients are referred. In IBS, cancer fears often remain, suggesting unconfident diagnosis or inadequate explanation.

Adolescent↗

Adjacent genetic markers on chromosome 11p15.5 at or near the tyrosine hydroxylase locus that show population linkage disequilibrium with each other do not show allelic association with bipolar affective disorder.

BACKGROUND: Linkage and association studies have suggested genetic susceptibility to bipolar affective disorder in a region of chromosome 11 around the tyrosine hydroxylase locus. We attempted to test the hypothesis that there was allelic association between polymorphisms around the tyrosine hydroxylase locus and bipolar affective disorder. METHODS: A case-control association study was employed using four polymorphic markers, which span a region of approximately 2 cM across the tyrosine hydroxylase locus. RESULTS: No evidence for allelic association between bipolar affective disorder and any of these markers was found. However, linkage disequilibrium between the markers was detected. CONCLUSIONS: This finding diminishes the probability that genes in this region influence susceptibility to bipolar affective disorder, at least in our sample.

Alleles↗

Human PBMC-derived dendritic cells transduced with an adenovirus vectorinduce cytotoxic T-lymphocyte responses against a vector-encoded antigen in vitro.

Dendritic cells (DC) are among the most potent antigen-presenting cells known and play an important role in the initiation of antigen-specific T-lymphocyte responses. Several recent studies have demonstrated that DC expressing vector-encoded tumor-associated antigens can induce protective and therapeutic immunity in murine cancer models. In the current study we set out to examine in vitro the utility of adenovirus vectors in the transduction of human DC for the induction of antigen-specific T-lymphocyte responses against a defined vector-encoded antigen. DC were derived from the adherent fraction of PBMC by culture in defined medium containing GM-CSF and IL-4. A replication-defective E1/E3-deleted type 5 adenovirus vector encoding bacterial beta-galactosidase (beta-gal) under the transcriptional control of a CMV promoter was used to transduce DC at multiplicities of infection (MOI) up to 1000. While high MOI were required to achieve efficient transduction there was no significant effect on DC morphology, immunophenotype or potency in allogeneic lymphocyte proliferation assays. Furthermore, transduced DC-induced antigen-specific CTL activity against adenoviral proteins and more significantly, the vector-encoded antigen beta-gal. These data clearly demonstrate the potential of adenovirus vectors in anticancer DC vaccine strategies and provide an important link between existing animal data and human clinical application.

Adenoviridae↗

Additional methadone increases craving for heroin: a double-blind, placebo-controlled study of chronic opiate users receiving methadone substitution treatment.

AIMS: To assess the acute-on-chronic effects of methadone on drug craving, mood and cognitive and psychomotor functioning in patients on long-term methadone substitution treatment. DESIGN AND PARTICIPANTS: A double-blind, cross-over design was used to compare the effects of a 33% increase in patient's daily dosage of methadone with a matched placebo linctus. Eighteen patients completed the study; all were assessed pre- and post-drug on two separate testing days. FINDINGS: Methadone significantly increased both positive craving (expected positive effects) and negative craving (expected relief of withdrawal discomfort) for heroin. Patients were unable to distinguish between methadone and placebo treatments. No differences between treatments emerged in cognitive or psychomotor effects. In terms of mood, patients were more alert and more contented following placebo than following methadone. CONCLUSIONS: Additional methadone may "prime" cravings for heroin in methadone substitution patients.

Adult↗

The hospice is dead.

Explore the source record for details and available documents.

Attitude of Health Personnel↗

Wide variation in lymphocyte steroid sensitivity among healthy human volunteers.

Steroids are frequently used to treat inflammatory conditions in which lymphocytes play a role. We have recently shown that in severe ulcerative colitis, treatment outcome correlates better with in vitro estimates of lymphocyte steroid sensitivity (LSS) than with disease severity. This lead us to examine the range and variability of LSS in the healthy population. Dexamethasone inhibition of lymphocyte proliferation was measured on 54 occasions in 18 volunteers (mean age, 46 yr; range, 23-60 yr) over an 8-month period. Inter- and intra-assay variation in LSS was low when expressed as maximum inhibition achieved, Imax (2.9% and 3.4%, respectively), allowing us to demonstrate a very wide variation in Imax between healthy individuals (-6.7% to 99.7%). In contrast, within-individual variation of Imax was significantly less than between-individual variation (F test, P < 0.0001), consistent with stability of this parameter over time. No correlation was seen between LSS and glucocorticoid receptor density or affinity, suggesting a postreceptor mechanism. Serum cortisol at the time of sampling and skin sensitivity to glucocorticoids also failed to correlate with LSS. This study suggests Imax is a sufficiently stable parameter to categorize healthy individuals according to LSS. The wide range of LSS demonstrated is striking and suggests that up to 30% of the healthy population would fail to respond to steroid therapy for severe inflammatory conditions.

Adult↗

Identification of a dynamic intracellular reservoir of CD86 protein in peripheral blood monocytes that is not associated with the Golgi complex.

In the process of developing a cancer immunotherapy strategy, we have identified and characterized a novel intracellular reservoir of CD86 protein in peripheral blood monocytes. This observation emerged from studies aimed at using retrovirus vectors to genetically modify tumor cells to express the costimulatory proteins CD80 and CD86. Retrovirus-mediated expression of CD80 and CD86 in T lymphoblastoid CEM cells resulted in an unexpected intracellular focal concentration of both proteins in the genetically modified cells. By extending these studies to an analysis of CD80 and CD86 expression in PBMC, we observed that endogenous CD86 expression in peripheral blood monocytes also involved a similar intracellular focal concentration of the protein. The intracellular concentration of CD86 in monocytes was not due to storage within the Golgi apparatus, and required intact microtubules to retain structural integrity. Furthermore, as the intensity of CD86 fluorescence increased on monocytes as a function of time in vitro, the intracellular focal concentration correspondingly decreased. These results are consistent with antegrade CD86 transport from an intracellular reservoir to the cell surface membrane. In this report, we detail the intracellular and membrane localization studies with tumor cell lines and PBMC, and describe the temporal relationship between intracellular storage and trafficking of CD86 to the cell surface membrane in peripheral blood monocytes. We hypothesize that this intracellular reservoir allows rapid and sustained deployment of an important costimulatory molecule to the monocyte surface membrane during initiation and maturation of the cell-mediated immune response.

Antigens, CD↗