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S Gibson

Publications and source records attributed to S Gibson.

At least 19 recordsLinked to original sources
PubMed2006

Prolonged function of macrophage, von Willebrand factor-deficient porcine pulmonary xenografts.

Porcine von Willebrand factor (vWF) activates human and primate platelets. Having determined the importance of pulmonary intravascular macrophages (PIMs) in pulmonary xenotransplantation, we evaluated whether, in the absence of PIMs, vWF might play a role in pulmonary xenograft dysfunction. Utilizing a left single-lung transplant model, baboons depleted of anti-alphaGal antibodies received lungs from either vWF-deficient (n = 2); MCP-expressing (n = 5); MCP PIM-depleted (n = 5); or vWF-deficient PIM-depleted swine (n = 3). Two out of three of the PIM-depleted, pvWF deficient grafts survived longer than any previously reported pulmonary xenografts, including PIM-depleted xenografts expressing human complement regulatory proteins. Depletion of PIM's from vWF-deficient lungs, like depletion of PIM's from hMCP lungs, resulted in abrogation of the coagulopathy associated with pulmonary xenotransplantation. Thus, in terms of pulmonary graft survival, control of adverse reactions involving pvWF appears to be equally or even more important than is complement regulation using hMCP expression. However, based on the rapid failure of PIM-sufficient, pvWF-deficient pulmonary xenografts, pVWF-deficient pulmonary xenografts appear to be particularly sensitive to macrophage-mediated damage. These data provide initial evidence that vWF plays a role in the 'delayed' (24 h) dysfunction observed in pulmonary xenotransplantation using PIM depleted hMCP organs.

Animals↗
PubMed2006

Investigation of the effect of a countywide protected learning time scheme on prescribing rates of ramipril: interrupted time series study.

BACKGROUND: Protected learning time (PLT) schemes have been set up in primary care across the UK. There is little published evidence of their effectiveness. OBJECTIVE: To investigate the effect of a PLT intervention for general practice to increase prescribing of ramipril for prevention of cardiovascular outcomes. DESIGN: Quasi-experimental, interrupted time series. SETTING: Lincolnshire, UK. METHODS: Prescribing data were analysed one year before and after the education for change in rate of increase of prescribing of ramipril, whether change in prescribing was related to postulated explanatory variables and to determine intervention costs. MAIN OUTCOME: The primary outcome was the rate of change of ramipril (10 mg) prescription items 12 months after compared with before the educational intervention. Secondary outcomes included cost. RESULTS: Ramipril prescribing at therapeutic dosage increased significantly (odds ratio 1.50, 95% CI 1.07-1.93) following education by 52,345 items (31,132 items at 10 mg) at a cost of pound 292k to pound 460k depending on formulation. This occurred despite a background of secular change. Most practices were represented by GPs, nurses or both during the education. Single-handed GPs were less likely to attend. Practices showed considerable variation in response to the educational intervention. The only predictor of whether practices increased in prescribing rate after the education was whether a practice nurse had undertaken specific diabetes training. Total list size, dispensing, training or single-handed status and GP attendance did not predict a change in prescribing. CONCLUSION: PLT schemes can contribute to beneficial changes in prescribing across a large geographical area.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2006

Expression of ETV6-NTRK in classical, cellular and mixed subtypes of congenital mesoblastic nephroma.

AIM: Congenital mesoblastic nephroma (CMN) is the commonest renal tumour of infancy, with classical, cellular and mixed histological subtypes described. A specific ETV6-NTRK3 fusion-gene product is reported in association with the cellular variant. The aim was to investigate the relationship between the presence of this product and morphological phenotype using paraffin-embedded archival material. METHODS AND RESULTS: Cases of CMN from a single centre during a 15-year period (1989-1994) were identified, anonymized and blindly classified using morphological criteria. RNA was extracted from frozen and paraffin sections for both conventional reverse transcriptase-polymerase chain reaction (RT-PCR) and quantitative real-time RT-PCR. Fifteen samples were analysed; two were non-informative and three expressed ETV6-NTRK3 using both techniques, two showing similar expression, whilst one showed expression two orders of magnitude lower, from a cellular tumour. All fusion positive cases were previously classified as cellular subtype. Six patients had mixed-subtype tumours in which the cellular components, morphologically indistinguishable from cellular tumours, were fusion negative, as were all classical cases. CONCLUSIONS: Real-time PCR Taqman assays, using both fixed and frozen tissue, provide highly reproducible detection and quantification of fusion transcript expression. Differences in expression levels may explain previous conflicting data on fusion gene detection in these tumours.

Humans↗
PubMed2005

On judgment and judgmentalism: how counselling can make people better.

Counsellors, like other members of the caring professions, are required to practise within an ethical framework, at least in so far as they seek professional accreditation. As such, the counsellor is called upon to exercise her moral agency. In most professional contexts this requirement is, in itself, unproblematic. It has been suggested, however, that counselling practice does present a problem in this respect, in so far as the counsellor is expected to take a non-judgemental stance and an attitude of "unconditional positive regard" toward the client. If, as might appear to be the case, this stance and attitude are at odds with the making of moral judgments, the possibility of an adequate ethics of counselling is called into question. This paper explores the nature and extent of the problem suggesting that, understood in a Kantian context, non-judgmentalism can be seen to be at odds with neither the moral agency of the counsellor nor that of the client. Instead, it is argued, the relationship between the non-judgmental counsellor and her client is a fundamentally moral relationship, based on respect for the client's unconditional worth as a moral agent.

Attitude of Health Personnel↗
PubMed2003

The importance of metabolic rate and the folly of body surface area calculations.

Mathematical formulae to calculate body surface area from measurements of height, weight and other parameters date from the late 19th century. Drug doses, fluid therapy, caloric requirements and physiological parameters such as cardiac output, glomerular filtration rate and a variety of respiratory function parameters are all frequently expressed in terms of a body surface area. Body surface area is often used in preference to body mass (weight). However, the original rationale for using body surface area as an estimate for metabolic rate has never been tested and the algorithms used to approximate body surface area have little evidence to support their use in this role. Recent developments in technology using indirect calorimetry allow easy measurement of metabolic rate in the clinical setting. Such measurements should be used for standardisation when weight alone is considered inadequate.

Anthropometry↗
PubMed2001

Rapid irreversible G protein alpha subunit misfolding due to intramolecular kinetic bottleneck that precedes Mg2+ "lock" after GTP/GDP exchange.

Stoichiometric exchange of GTP for GDP on heterotrimeric G protein alpha (Galpha) subunits is essential to most hormone and neurotransmitter initiated signal transduction. Galphas are stably activated in a Mg2+ complex with GTPgammaS, a nonhydrolyzable GTP analogue that is reported to bind Galpha, with very high affinity. Yet, it is common to find that substantial amounts (30-90%) of purified G proteins cannot be activated. Inactivatable G protein has heretofore been thought to have become "denatured" during formation of the obligatory nucleotide-free or empty (MT) Galpha-state that is intermediary to GDP/GTP exchange at a single binding site. We find Galpha native secondary and tertiary structure to persist during formation of the irreversibly inactivatable state of transducin. MT Galpha is therefore irreversibly misfolded rather than denatured. Inactivation by misfolding is found to compete kinetically with protective but weak preequilibrium nucleotide binding at micromolar ambient GTPgammaS concentrations. Because of the weak preequilibrium, quantitative protection against Galpha aggregation is only achieved at free nucleotide concentrations 10-100 times higher than those commonly employed in G protein radio-nucleotide binding studies. Initial GTP protection is also poor because of the extreme slowness of an intramolecular Galpha refolding step (isomerization) necessary for GTP sequestration after its weak preequilibrium binding. Of the two slowly interconverting Galpha x GTP isomers described here, only the second can bind Mg2+, "locking" GTP in place with a large net rise in GTP binding affinity. A companion Galpha x GDP isomerization reaction is identified as the cause of the very slow spontaneous GDP dissociation that characterizes G protein nucleotide exchange and low spontaneous background activity in the absence of GPCR activation. Galpha x GDP and Galpha x GTP isomerization reactions are proposed as the dual target for GPCR catalysis of nucleotide exchange.

Animals↗
PubMed2001

Comparison of test characteristics of urine dipstick and urinalysis at various test cutoff points.

STUDY OBJECTIVE: We compare the test characteristics of urine dipstick and urinalysis at various test cutoff points in women presenting to emergency departments and an intermediate care center with symptoms of urinary tract infection. METHODS: This was a prospective, observational study of adult women presenting to 1 of 2 community hospital EDs or an intermediate care center with dysuria, urgency, or urinary frequency on history, or suprapubic or costovertebral angle tenderness on examination. Patients who had taken antibiotics in the past 72 hours, had indwelling Foley catheters, symptomatic vaginal discharge, diabetes mellitus, immunodeficiency disorders, or were unable to provide a reliable history were excluded. The patient's clean-catch or catheterized urine specimen was tested immediately by a nurse using a Multistix 9 SG reagent strip. A second aliquot was sent within 1 hour of collection to the hospital laboratory, where a semiautomated microscopic urinalysis and a urine culture were performed. A positive urine culture was defined as more than 100,000 colonies of 1 or 2 uropathogenic bacteria per mL of urine at 48 hours. Dipstick and urinalysis data were compared with urine culture results. Sensitivity, specificity, and predictive values were calculated at various definitions of a positive test, or "test cutoff points," for combinations of leukocyte esterase, nitrite, and blood on dipstick and for RBCs and WBCs on urinalyses. The probability of an erroneous decision to withhold treatment on the basis of a negative test result was defined as "undertreatment," or 1 minus the negative predictive value. "Overtreatment" was defined as 1 minus the positive predictive value. RESULTS: Three hundred forty-three patients were enrolled in this study. Twelve patients were withdrawn because of missing laboratory results. Forty-six percent (152/331) of patients had positive urine cultures. If urine dipstick results are defined as positive when leukocyte esterase or nitrite is positive or blood is more than trace, the overtreatment rate is 47% (156/331) and the undertreatment rate is 13% (43/331). If urinalysis results are defined as positive when WBCs are more than 3 per high-power field or RBCs are more than 5 per high-power field, the overtreatment rate is 44% (146/331) and the undertreatment rate is 11% (36/331). Matched pairs of test characteristics were identified when the analysis was repeated using more than 10,000 colonies per mL as a positive culture. CONCLUSION: In this patient population, similar overtreatment and undertreatment rates were identified for various test cutoff points for urine dipstick tests and urinalysis. Although a urine dipstick may be equivalent to a urinalysis for the diagnosis of urinary tract infection, the limitations in the diagnostic accuracy of both tests should be incorporated into medical decisionmaking.

Adolescent↗
PubMed2001

Nutritional status in elderly female hip fracture patients: comparison with an age-matched home living group attending day centres.

Fractured neck of femur occurs mostly in the older female population and is generally caused by falls. Malnutrition has been postulated as a factor that increases the tendency to suffer falls. Nutritional status of older female hospital patients admitted for emergency surgery for fractured neck of femur recruited (n 75), was compared with an age-matched independent-living group of females attending one of three local day centres (n 50). Dietary assessment was undertaken using three consecutive 24 h dietary recalls and, in the hip fracture group, completed menu cards were used as memory prompts. Data concerning key lifestyle characteristics were obtained using a face-to-face administered questionnaire. Blood samples were taken to determine levels of plasma albumin, transferrin, C-reactive protein (CRP), cholesterol, vitamin C, Se, Zn and total antioxidant status. Haemolysate samples were analysed for Se-dependent glutathione peroxidase activity. There were no significant differences in age between the two groups, but the hip fracture patients had lower mean values for body weight (59.6 v. 67.5 kg; mindex (weight/demispan) (83.1 v. 94.4 kg/m; calculated BMI (24.1 v. 27.5 kg/m2 mid-upper arm circumference; 27.1 v. 31.3 cm, and triceps skinfold thickness; 17.0 v. 18.9 mm, than the home-living group. The hip fracture patients had lower intakes of energy (4.3 v. 5.4 MJ, fat carbohydrate protein thiamine vitamin B6 calcium K Mg P Fe Se and NSP Mean intakes of both groups were below the estimated average requirement for energy and below the reference nutrient intakes for folate, Ca, vitamin D, Mg, K, Se and Zn. In a high percentage of the hip fracture group the dietary intake of particular nutrients fell below the lower reference nutrient intake for Se (73 %), Mg (54 %) and Fe (19 %). As expected, the fracture patients had reduced plasma albumin and increased CRP values. They had higher plasma vitamin C levels and lower cholesterol levels than the day centre attendees. There were no significant differences in plasma levels of Se, Zn, transferrin or haemolysate glutathione peroxidase activity between the two groups. However, there was evidence of under-nutrition in both groups as key anthropometric values were low, plasma nutrient and metabolite levels were below the standard reference ranges and many individuals had low dietary intakes for specified nutrients.

Aged↗
PubMed2001

Dietary sugars and micronutrient dilution in normal adults aged 65 years and over.

OBJECTIVE: To examine the relationship between non-milk extrinsic sugars (NMES) concentration and micronutrient intakes and status in free-living older people. DESIGN: The National Diet and Nutrition Survey of people aged 65 years and over; a cross-sectional study in Britain in 1994/5. SUBJECTS AND METHODS: Eight hundred and six men and women living in private households who were not on medication for nutritional disorders. Subjects were classified into four groups (Q1 to Q4), using cut-off points corresponding to quartiles of energy from NMES. Relationships were examined between dietary NMES concentration and intakes of calcium, iron, riboflavin, folate, vitamin C and vitamin D. Status indices were also assessed in each group. RESULTS: Overall, a small proportion of men and women had intakes below the Lower Reference Nutrient Intake (LRNI) for calcium, iron, folate, riboflavin or vitamin C, while vitamin D intakes were universally low. Intakes of micronutrients tended to be highest at moderate levels of NMES in the diet (Q2 and Q3, equivalent to 8-15% of energy from NMES). Micronutrient status was low for riboflavin in 38% of the sample, while 15% had low vitamin C status and more than 10% were anaemic. There was little evidence that poorer nutrient status was associated with higher levels of dietary NMES. Although some indices of folate status were lower in Q4, this is most likely to reflect confounding by smoking. Energy intake accounted for 20-40% of the variance in micronutrient intakes, compared with less than 5% for NMES concentration. CONCLUSIONS: A diet moderately high in NMES (up to around 15% of energy) is unlikely to have a detrimental impact on micronutrient intake or status in this age group. Energy intake is the major determinant of micronutrient adequacy.

Aged↗
PubMed2001

Episodic evolution of growth hormone in primates and emergence of the species specificity of human growth hormone receptor.

Growth hormone (GH) evolution is very conservative among mammals, except for primates and ruminant artiodactyls. In fact, most known mammalian GH sequences differ from the inferred ancestral mammalian sequence by only a few amino acids. In contrast, the human GH sequence differs from the inferred ancestral sequence by 59 amino acids. However, it is not known when this rapid evolution of GH occurred during primate evolution or whether it was due to positive selection. Also, human growth hormone receptor (GHR) displays species specificity; i.e., it can interact only with human (or rhesus monkey) GH, not with nonprimate GHS: The species specificity of human GHR is largely due to the Leu-->Arg change at position 43, and it has been hypothesized that this change must have been preceded by the His-->Asp change at position 171 of GH. Is this hypothesis true? And when did these changes occur? To address the above issues, we sequenced GH and GHR genes in prosimians and simians. Our data supported the above hypothesis and revealed that the species specificity of human GHR actually emerged in the common ancestor of Old World primates, but the transitional phase still persists in New World monkeys. Our data showed that the rapid evolution of primate GH occurred during a relatively short period (in the common ancestor of higher primates) and that the rate of change was especially high at functionally important sites, suggesting positive selection. However, the nonsynonymous rate/synonymous rate ratio at these sites was <1, so relaxation of purifying selection might have played a role in the rapid evolution of the GH gene in simians, possibly as a result of multiple gene duplications. Similar to GH, GHR displayed an accelerated rate of evolution in primates. Our data revealed proportionally more amino acid replacements at the functionally important sites in both GH and GHR in simians but, surprisingly, showed few coincidental replacements of amino acids forming the same intermolecular contacts between the two proteins.

Amino Acids↗
PubMed2001

No association of an interleukin 4 gene promoter polymorphism with Graves' disease in the United Kingdom.

Graves' disease (GD) is an autoimmune thyroid disease of unknown etiology, although predisposition to the development of this disease is thought to be caused by both genetic and environmental factors. Recently, an association between a promoter polymorphism of the interleukin 4 gene and GD has been reported. A C-T base change at position -590 showed modest protection against the development of GD in a United Kingdom data set of 135 patients with GD and 101 controls. This polymorphism was, therefore, investigated in a much larger case-control cohort of 384 patients with GD and 288 control subjects using PCR, followed by restriction fragment length polymorphism analysis. No protective effect of the T allele of this polymorphism was observed in our data set, and indeed no significant difference in either allelic or genotypic distribution was seen between the patient and control groups. Moreover, calculation of probabilities indicate that the original study lacked sufficient power to support the conclusions drawn. Our data support the hypothesis that the C-T promoter polymorphism of the interleukin 4 gene does not confer protection against the development of GD in Caucasians in the United Kingdom.

Alleles↗
PubMed2001

A randomized controlled trial of the effects of multi-sensory stimulation (MSS) for people with dementia.

OBJECTIVES: To investigate short-term effects of Multi-Sensory Stimulation (MSS) on behaviour, mood and cognition of older adults with dementia, the generalization of effects to day hospital and home environments and the endurance of any effects over time. DESIGN: A randomized controlled trial comparing MSS with a credible control of one-to-one activities. METHODS: Fifty patients with diagnoses of moderate to severe dementia were randomized to either MSS or Activity groups. Patients participated in eight 30-minute sessions over a 4-week period. Ratings of behaviour and mood were taken before, during and after sessions to investigate immediate effects. Pre, mid, post-trial, and follow-up assessments were taken to investigate any generalization of effects on cognition, behaviour at the day hospital and behaviour and mood at home and endurance of effects once sessions had ceased. RESULTS: Immediately after MSS and Activity sessions patients talked more spontaneously, related better to others, did more from their own initiative, were less bored/inactive, and were more happy, active or alert. Both groups were more attentive to their environment than before, with a significantly greater improvement from the MSS group. At the day hospital, patients in the Activity group improved on their 'speech skills' (amount of speech; initiation of speech), whereas the MSS group remained unchanged during the trial. The MSS group showed a significant improvement in mood and behaviour at home compared to the Activity group whose behaviour deteriorated. No longer-term benefits were shown; indeed, behaviour declined sharply during the month follow-up period. CONCLUSIONS: Both MSS and Activity sessions appear to be effective and appropriate therapies for people with dementia.

Acoustic Stimulation↗
PubMed2000

Antisense-mediated inhibition of the bcl-2 gene induces apoptosis in human malignant glioma.

BACKGROUND: The bcl-2 protooncogene represses a number of cellular apoptotic pathways and is known to be expressed in increasing amounts in glial tumors of higher malignancy. We tested whether antisense oligonucleotides to the bcl-2 gene would affect glioma cell viability. METHODS: Antisense oligonucleotides directed to the first six codons of the human bcl-2 gene, and nonsense oligonucleotides as a control, were transfected into malignant glioma cells. Two human Bcl-2 positive glioblastoma cell lines from our tumor bank (Jon52 and Roc) were both transfected in vitro with bcl-2 antisense (AS) and nonsense (NS) oligonucleotides at 1 microm and 5 microm concentrations for 5 and 24 hr. Cell viability was assessed at 2, 4, 5, and 7 days by using an MTT mitogenic assay and by cell counting via direct visualization using a hemocytometer. RESULTS: There was up to a log-fold decrease in cell growth of the bcl-2 AS treated cells compared to the NS transfected cells for both Roc (p = 0.007 and p = 0.004) and Jon52 (p = 0.02 and p = 0.004) at 5 and 24 hr of transfection. There was as much as 50% cytotoxicity in both glioblastoma cell lines at 1 microm and 5 microm concentrations after 24 hr transfection with AS bcl-2 oligonucleotides (all p < 0.01). Western blot analysis demonstrated a decrease in the expression of the Bcl-2 protein in one cell line, whereas there was a statistically significant increase in the apoptotic index of both cell lines (p < 0.05 by chi square analysis). CONCLUSIONS: Our results suggest that transfection of human glioma cells with antisense bcl-2 results in an increase in apoptotic death. This provides evidence that Bcl-2 plays a role in tumor progression of glioma by acting as an oncogene, and suggests that inhibition of the bcl-2 gene could have a therapeutic effect.

Aged↗