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Biomedical subjects

G Nicholson

Publications and source records attributed to G Nicholson.

At least 19 recordsLinked to original sources
PubMed2006

Herbicide exposure modifies GSTP1 haplotype association to Parkinson onset age: the GenePD Study.

BACKGROUND: Polymorphisms in the glutathione S-transferase pi gene (GSTP1), encoding GSTP1-1, a detoxification enzyme, may increase the risk of Parkinson disease (PD) with exposure to pesticides. Using the GenePD Study sample of familial PD cases, we explored whether GSTP1 polymorphisms were associated with the age at onset of PD symptoms and whether that relation was modified by exposure to herbicides. METHODS: Seven single-nucleotide polymorphisms (SNPs) were genotyped and tested for association with PD onset age in men in three strata: no exposure to herbicides, residential exposure to herbicides, and occupational exposure to herbicides. Haplotypes were similarly evaluated in stratified analyses. RESULTS: Three SNPs were associated with PD onset age in the group of men occupationally exposed to herbicides. Three additional SNPs had significant trends for the association of PD onset age across the herbicide exposure groups. Haplotype results also provided evidence that the relation between GSTP1 and onset age is modified by herbicide exposure. One haplotype was associated with an approximately 8-years-earlier onset in the occupationally exposed group and a 2.8-years-later onset in the nonexposed group. CONCLUSIONS: Herbicide exposure may be an effect modifier of the relation between glutathione S-transferase pi gene polymorphisms and onset age in familial PD.

Disease Susceptibility↗
PubMed2006

Basidiochrome -- a novel siderophore of the Orchidaceous Mycorrhizal Fungi Ceratobasidium and Rhizoctonia spp.

A novel trishydroxamate siderophore, named basidiochrome, was isolated as the principal siderophore from low-iron culture filtrates of Ceratobasidium and Rhizoctonia species which are known as mycorrhizal fungi associated with orchid roots. Ion-exchange chromatography and preparative HPLC yielded a pure compound which contained two components according to GC-MS analysis: L: -N(5)-hydroxy-ornithine and 3-methyl-2-cis-pentenedioic acid (3-methyl-cis-glutaconic acid). FTICR-ESI-MS of both the iron-free and ferric form indicated an elemental composition of C(33)H(47)N(6)O(16)Fe (MW = 839) for the ferric form of basidiochrome. The connectivity was further elucidated by 2D-NMR techniques (HSQC, HMBC, COSY, NOESY) indicating that basidiochrome is a novel linear tripeptide consisting of three L: -N(5)-hydroxy-ornithines each linked to 3-methyl-2-cis-pentenedioic acid residues.

Basidiomycota↗
PubMed2006

Nurse led flexible sigmoidoscopy in primary care--the first thousand patients.

OBJECTIVES: Secondary care Trusts have traditionally been providers of flexible sigmoidoscopy services in the United Kingdom. The aim of this study was to establish a Nurse-led flexible sigmoidoscopy clinic that would provide a patient orientated service in a primary care setting. PATIENTS AND METHODS: A protocol driven flexible sigmoidoscopy clinic was established in a primary care setting. The first thousand patients who underwent flexible sigmoidoscopy at the community clinic were prospectively studied. RESULTS: A nurse endoscopist performed 1002 procedures on 1000 patients. Median time from referral to flexible sigmoidoscopy was 35 days (Range 1-180 days). Two hundred and twenty-two (22%) patients were diagnosed with significant colonic pathology including 25 (2.5%) patients with colorectal cancer. Median time from referral to histological diagnosis of colorectal cancer was 26 days (range 7-87 days). No complications were encountered. Patients who required further follow-up were referred to a Consultant led (29%) or Nurse led clinic (5%) in secondary care. Patient satisfaction as assessed by postal questionnaire indicated that 447 (99%) patients were satisfied with the service. CONCLUSIONS: A community endoscopy clinic can provide a safe and effective flexible sigmoidoscopy service with high levels of patient satisfaction. Nurse Endoscopists can extend their role in primary care with adequate training and support from secondary care hospitals.

Ambulatory Care↗
PubMed2006

Lupus nephritis in an Afro-Caribbean population: renal indices and clinical outcomes.

In an Afro-Caribbean population, 111 new cases of systemic lupus erythematosus were diagnosed in the 10-year period from January 1995. Fifty-three cases (48%) presented with or subsequently developed lupus nephritis (SLEN). We recorded clinical characteristics and treatment outcomes of SLEN. We retrospectively categorized patients into four groups based on presence or absence of proteinuria with or without renal impairment. Group 1 (n = 15, 28%) had normal renal function (creatinine clearance (CrCl) > 70 mL/minute) with urinary protein excretion (UPE) of 0.5-3.0 g/24 hour, group 2 (n = 7, 13%) had normal renal function with UPE > 3.0 g/24 hour, group 3 (n = 9, 17%) had renal impairment (CrCl < 70 mL/minute) with UPE of 0.5-3.0 g/24 hour and group 4 (n = 22, 42%) had renal impairment with UPE > 3.0 g/24 hour. Renal biopsies were performed in 15 patients (28%). The number of treated patients in-remission decreased across the groups, from 100% in group 1 and 71% in group 2, to 33% in group 3 and 32% in group 4 (Pr < 0.001). There were 12 deaths from renal causes: none in groups 1 and 2, two (22%) from group 3 and 10 (45%) from group 4 (Pr = 0.003). In resource-poor clinical settings with limited access to histopathological services, CrCl and UPE may be useful predictors of therapeutic response and clinical outcomes in SLEN.

Adult↗
PubMed2005

BDNF genetic variants are associated with onset age of familial Parkinson disease: GenePD Study.

Brain-derived neurotrophic factor (BDNF) stimulates neuronal growth and protects nigral dopamine neurons in animal models of Parkinson disease (PD). Therefore, BDNF is a candidate gene for PD. The authors investigated five single-nucleotide polymorphisms in 597 cases of familial PD. Homozygosity for the rare allele of the functional BDNF G196A (Val66Met) variant was associated with a 5.3-year older onset age (p = 0.0001). These findings suggest that BDNF may influence PD onset age.

Age of Onset↗
PubMed2005

Maternal and neonatal side-effects of remifentanil patient-controlled analgesia in labour.

BACKGROUND: Remifentanil has been suggested as an ideal opioid for patient-controlled analgesia (PCA) in labour, but the safety profile has not been established. The aims of this preliminary prospective observational study were to investigate the maternal side-effects and early neonatal effects, and to assess the placental transfer of remifentanil PCA during labour. METHODS: Women with no known obstetric complications or contraindication to remifentanil were recruited (n=50). Remifentanil was administered at a bolus dose of 0.5 microg kg(-1) and a lockout period of 2 min. A visual analogue scale was used to assess pain, nausea and itching. Maternal observations were recorded hourly and fetal heart rate trace was assessed every 2 h. Umbilical cord gases, 1 and 5 min Apgar scores and neurological evaluation of the neonate were recorded. Maternal venous blood and umbilical artery and vein cord blood samples were collected for analysis of remifentanil concentration. RESULTS: Fifty women enrolled in the study (24 multiparous, 26 primiparous). There was no evidence of cardiovascular instability or respiratory depression. Pain scores decreased significantly, but there was no significant change in nausea after initiating the PCA. A statistically significant increase in itching was found to be clinically mild and 22 women were slightly drowsy (95% confidence interval [CI], 30-58.7%) but alert to voice. Ten fetal heart rate traces demonstrated changes in the first 20 min, but did not require intervention (95% CI, 10-33.7%). The median 1 and 5 min Apgar scores were 9. The mean umbilical cord gases and neurological examination were within normal limits. Maternal vein and umbilical vein cord samples demonstrated placental transfer of remifentanil, and small amounts were detected in umbilical artery samples. CONCLUSIONS: At the bolus dose used remifentanil PCA has an acceptable level of maternal side-effects and minimal effect on the neonate. Remifentanil crosses the placenta and appears to be either rapidly metabolized or redistributed in the neonate.

Adolescent↗
PubMed2005

The hormonal and inflammatory responses to pelvic reconstructive surgery following major trauma.

Patients undergoing trauma sustain an initial injury followed by further physiological challenges during surgery. Plasma osteocalcin (OC), a marker of osteoblastic activity, declines after major surgery. Increased cortisol secretion, and other components of the perioperative stress response, may play a role in mediating this response. We have examined the osteocalcin, hormonal and cytokine responses in twenty patients undergoing post-traumatic pelvic reconstruction surgery. We measured plasma osteocalcin, serum cortisol, bone specific alkaline phosphatase (BSAP), IL-6, IL-8, IL-10, plasma epinephrine and norepinephrine concentrations for up to 3 days after surgery. We recorded an increase in IL-6, IL-10 and epinephrine concentrations perioperatively and a fall in OC and BSAP concentrations. There were no significant changes in cortisol or IL-8 concentrations. Patients undergoing pelvic reconstruction surgery following trauma have a preserved inflammatory and catecholamine response but the cortisol response may be obtunded. Osteocalcin concentrations are affected by factors other than glucocorticoids.

Adolescent↗
PubMed2004

Blood pack fault monitoring.

BACKGROUND AND OBJECTIVES: The National Blood Service (NBS) has recalled blood components as a result of manufacturing faults, or defective blood pack component parts leading to the possibility of an 'open' system. There has been an increase in the complexity of blood packs as a result of leucodepletion, sample diversion and sampling. The NBS implemented a mechanism to collate and analyse blood pack faults as a safety and quality initiative in conjunction with blood pack manufacturers. MATERIALS AND METHODS: Standard reporting forms were produced and implemented at all Centres. The forms were collated and analysed using statistical analysis software. Control charts were used to identify trends for specific faults, which were resolved with the relevant manufacturer. RESULTS: The overall defect rate per million for the three main blood pack manufacturers used by the NBS for the respective periods 2001, 2002 and 2003, were as follows: Manufacturer A, 1076, 1396 and 954; Manufacturer B, 1496, 1301 and 2169; and Manufacturer C, 1871, 1253 and 1392. CONCLUSIONS: Monitoring and analysis of blood pack faults has resulted in the identification and rectification of specific problems associated with blood pack manufacture and use. Close collaboration with manufacturers has enabled effective remedial action. Wider collation of data would provide an early warning of potential areas of concern.

Blood Banking↗
PubMed2003

Salmochelins, siderophores of Salmonella enterica and uropathogenic Escherichia coli strains, are recognized by the outer membrane receptor IroN.

Members of a family of catecholate siderophores, called salmochelins, were isolated by reversed-phase HPLC from Salmonella enterica serotype Typhimurium and structurally characterized by Fourier transform ion cyclotron resonance-MSMS and GC-MS. The tentative structure of salmochelin 1 contained two 2,3- dihydroxybenzoylserine moieties bridged by a glucose residue, bound to the serine hydroxyl group of one moiety and the carboxylate of the second moiety. Salmochelin 2 contained in addition a second glucose residue linked to a third 2,3-dihydroxybenzoylserine moiety. Salmochelins were not produced by an iroBC mutant, which indicated that the IroB protein might be responsible for the glucosyl transfer predicted by sequence similarities to known glycosyltransferases. Uptake experiments with radiolabeled (55)Fe-salmochelin and growth promotion tests with salmochelins showed that the IroN outer membrane receptor, encoded in the iroA locus of S. enterica and uropathogenic Escherichia coli strains, was the main receptor for ferric salmochelin transport.

Cell Membrane↗
PubMed2003

A reassessment of genetic diversity in Icelanders: strong evidence from multiple loci for relative homogeneity caused by genetic drift.

There has been some controversy in the literature concerning whether Icelanders are genetically homogenous or heterogeneous relative to other European populations. We reassess this question in the light of large data sets spanning 83 autosomal SNP loci, 14 serogenetic loci, 6622 Y-chromosomes and 3214 sequences from mtDNA hypervariable segments 1 and 2 (HVS1 and HVS2). Our results strongly support the hypothesis that genetic drift, with a consequent loss of variation, has had a greater impact on Icelanders than most other Europeans. We also analyse 7245 HVS1 sequences from 25 European populations. In line with other studies, we observe a deficit of rare HVS1 haplotypes and an excess of intermediate frequency haplotypes in Icelanders compared to most European populations, with some measures of genetic diversity indicating relative heterogeneity and others indicating relative homogeneity of Icelanders. Simulations indicate that genetic drift, and not admixture (as proposed by Arnason, 2003) is the most likely cause of the atypical Icelandic HVS1 frequency spectrum. These simulations reveal that gene diversity (heterozygosity) and mean pairwise differences are largely insensitive to events in recent population history, while statistics based on the number of haplotypes or segregating sites are much more sensitive. Overall, our analyses strongly indicate that the Icelandic gene pool is less heterogeneous than those of most other European populations.

Chromosomes, Human, Y↗
PubMed2003

Comparison of L-bupivacaine 0.75% and lidocaine 2% with bupivacaine 0.75% and lidocaine 2% for peribulbar anaesthesia.

BACKGROUND: L-Bupivacaine has a safer side-effect profile than bupivacaine. We compared the efficacy of a mixture of L-bupivacaine 0.75% and lidocaine 2% with bupivacaine 0.75% and lidocaine 2% for peribulbar anaesthesia in cataract surgery. METHODS: Ninety patients were allocated randomly to receive 8 ml of a mixture of equal parts of bupivacaine 0.75% and lidocaine 2% or an equal volume of L-bupivacaine and lidocaine 2%. Hyaluronidase 15 IU ml(-1) was added to both solutions. RESULTS: There were significant differences between the groups in clinical end-points. The median time at which the block was adequate to start surgery was 4 min (interquartile range 4-8 min) in the bupivacaine group and 8 min (5-12 min) in the L-bupivacaine group (P=0.002). Median ocular and eyelid movement scores were similarly significantly decreased in the bupivacaine group compared with the L-bupivacaine group at all times (P</=0.03). There was no difference between groups in the incidence of minor complications. CONCLUSIONS: A mixture of bupivacaine 0.75% and lidocaine 2% provides faster onset time than a mixture of L-bupivacaine 0.75% and lidocaine 2%.

Adult↗
PubMed2003

The development of an oral antidiabetic combination tablet: design, evaluation and clinical benefits for patients with type 2 diabetes.

Type 2 diabetes is a chronic and progressive disease. Oral antidiabetic monotherapies directly address only one defect as their primary mechanism of action, and do not control blood glucose sufficiently well to meet current glycaemic targets. In consequence, most patients need combination therapy within a few years. However, the co-administration of two or more oral antidiabetic drugs may render treatment regimens difficult to follow. Combining oral antidiabetic agents into a single tablet provides a means of intensifying antidiabetic therapy while supporting good patient compliance. An insulin sensitiser and an insulin secretagogue represent a rational oral antidiabetic combination, as they address the dual endocrine defects of insulin resistance and impaired beta-cell function in type 2 diabetes. Nevertheless, the components of a combination tablet must be carefully chosen. Metformin (an insulin sensitiser) and glibenclamide (an insulin secretagogue) are well supported by decades of clinical evidence, and the pharmacokinetics of these agents support twice-daily co-administration. The final technical challenge is to optimise their delivery within a single-tablet combination. A recently-introduced metformin-glibenclamide combination tablet (Glucovance) has been extensively studied in well-designed clinical trials, where it has been shown to be more effective than its component monotherapies in controlling fasting and postprandial glycaemia. This treatment provides a case study in the development of a single-tablet oral antidiabetic combination, in terms of the pharmacokinetic issues facing the development of this preparation, and the implications of the pharmacokinetic properties of the components of the combination tablet on their pharmacodynamic actions and risk-benefit profile.

Administration, Oral↗
PubMed2002

Chemical composition of the attachment pad secretion of the locust Locusta migratoria.

This study is the first attempt to characterise the chemical composition of the secretion of the smooth pads of the locust Locusta migratoria and to relate this to the composition of the cuticle coverage of the pads and the wings. Gas-chromatography and mass-spectrometry (GC-MS) were the principal techniques used for the characterization of these materials. Secretion droplets were visualised and quantified with the aid of diverse microscopic techniques. The chemical composition of prints is shown to differ from the cuticle coverage, in particular, with respect to the fatty acid distribution: in the secretion, saturated and unsaturated fatty acids with chain lengths between C(16) and C(20) in both the free form and as glycerides predominate, whereas cuticle coverage contains waxes of long-chained fatty-acids bound to long-chain primary alcohols. The second important difference is the significant amount of glucose and other saccharides found in methanolyzates of the pad fluid. A considerable amount of the amino acids (up to 53%) was detected in the non-volatile portion of the fluid. Data obtained from the shock-freezing, carbon-platinum coating and replica preparation show that the secretory droplets contain nano-droplets on their surfaces. The results lead us to suggest that the pad secretion is an emulsion consisting of lipidic nano-droplets dispersed in an aqueous liquid. According to the chemical composition of the secretion, a high-viscosity of the fluid may be suggested. Presumably, the fluid is a kind of a coupling agent, promoting and strengthening adhesion between otherwise incompatible materials by providing the proximity of contact for intermolecular forces.

Amino Acids↗
PubMed2002

Osteocalcin and the hormonal, inflammatory and metabolic response to major orthopaedic surgery.

Plasma osteocalcin, a marker of osteoblastic activity, decreases after major abdominal and gynaecological surgery. Increased cortisol secretion and other hormonal and inflammatory components of the peri-operative stress response may play a role in mediating this response. We assessed the effects of three different anaesthetic techniques on peri-operative osteocalcin concentrations. Thirty-six female patients undergoing elective total hip replacement were randomly assigned to receive propofol, propofol plus 'three-in-one' block or etomidate as part of a general anaesthetic technique. We measured plasma osteocalcin and serum cortisol, bone specific alkaline phosphatase, interleukin-6, plasma epinephrine, norepinephrine, plasma glucose and cystatin C concentrations for up to 3 days after surgery. Etomidate successfully inhibited the cortisol response to surgery but plasma osteocalcin declined in all patients. This was accompanied by increased plasma catecholamines, interleukin-6 and glucose concentrations, and decreased cystatin C-values. Inhibition of the cortisol response to surgery failed to prevent a decrease in plasma osteocalcin concentrations after surgery, suggesting that other factors such as cytokines or catecholamines may play a significant role.

Aged↗
PubMed2002

Parkinson's disease and anaesthesia.

Parkinson's disease is an increasingly common disease of elderly patients who present a particular anaesthetic challenge. This review explores the epidemiology, aetiology, pathogenesis, and pathophysiology of the condition, particularly the possible role of genetic factors. The clinical features are described in detail and recent advances in medical management are highlighted. Controversies surrounding the use of the newer drugs and possible advances in neurosurgical interventions are discussed. Particular anaesthetic problems in patients with Parkinson's disease are respiratory, cardiovascular, and neurological. Potential drug interactions are described and recommendations are made about suitable anaesthetic techniques.

Anesthesia↗
PubMed2002

Autosomal dominant juvenile amyotrophic lateral sclerosis and distal hereditary motor neuronopathy with pyramidal tract signs: synonyms for the same disorder?

Autosomal dominant juvenile amyotrophic lateral sclerosis (ALS) is a rare disorder and so far only one family has been reported. Genetic linkage studies mapped the disease locus to chromosome 9q34 (ALS4). The diagnosis of ALS in this family is based on the clinical signs with almost exclusively lower motor neurone pathology in combination with less prominent pyramidal tract signs. Atypical features include normal life expectancy, the absence of bulbar involvement and the symmetrical distal distribution of atrophy and weakness. We performed a molecular genetic study in three families that we had diagnosed as having distal hereditary motor neuronopathy, i.e. distal spinal muscular atrophy or spinal Charcot-Marie-Tooth syndrome, and found linkage to the ALS4 locus. The clinical phenotype in these three families, of different geographic origin (Austria, Belgium and England), is strikingly similar to the autosomal dominant juvenile ALS family except for a younger onset age in two of the distal hereditary motor neuronopathy families. These data suggest that ALS4 and distal hereditary motor neuronopathy with pyramidal tract signs may be one and the same disorder.

Adolescent↗