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61.
AP Tamhankar FAK Mazari NJ Everitt K Ravi 《Annals of the Royal College of Surgeons of England》2009,91(6):460-463
INTRODUCTION
Patient-directed information available on the internet is not always regulated; it may be confusing and sometimes just overwhelming. We aimed to establish the proportion of patients undergoing two common surgical procedures, who searched the internet for information about their operations and to assess the usefulness of the information they received.PATIENTS AND METHODS
A total of 105 consecutive patients undergoing elective abdominal wall hernia repair (n = 54) or laparoscopic cholecystectomy (n = 51) in a single surgical firm were included in the study. Patients were counselled about their operation in pre-operative assessment clinics and standard trust information leaflets were provided without any mention of this study. Patients were then asked to complete a questionnaire on the morning of their operation.RESULTS
All patients completed the questionnaire. Of the patients, 59% stated that they had access to the internet and 77% of these accessed the internet over 2 h a week. Of the patients with internet access, 31% used it to acquire additional information about their operations and 58% used internet search engines. Of the patients who searched the internet regarding their operations, 26% were confused and/or worried by the information they received.CONCLUSIONS
A significant proportion of patients undergoing common surgical procedures used the internet and about one-third of them specifically sought information about their operation on the internet. Such information can cause worry and confusion in patients. Our study highlights the need for regulated, comprehensible, patient information on hospital websites to which patients should be directed. 相似文献62.
Rana BK Insel PA Payne SH Abel K Beutler E Ziegler MG Schork NJ O'Connor DT 《Hypertension》2007,49(1):96-106
The influence of genetic contributors, such as common single nucleotide polymorphisms, on blood pressure and essential hypertension may vary with the gender. We used the power of a large, community-based sample to probe whether gender interacts with genes in contributing to extremes of blood pressure in 611 male and 656 female age-matched white Americans within the top and bottom 5th percentiles of blood pressure among >53 000 people in a health maintenance program. This approach has >90% statistical power to detect genes contributing as little as 3% to trait (blood pressure) variation. We scored approximately 60 000 genotypes in the subjects: 48 single nucleotide polymorphisms at 33 autosomal and 2 X-linked genes in adrenergic and renal pathways that regulate blood pressure. Six individual variants significantly affected blood pressure and demonstrated gene-by-gender interaction, yielding different effects of the single nucleotide polymorphism on blood pressure in males and females. In females, polymorphisms at beta(1)-adrenergic receptor and alpha(2A)-adrenergic receptor contributed to blood pressure, whereas in men, polymorphisms at beta(2)-adrenergic receptor and angiotensinogen were associated. An alpha(2A)-adrenergic receptor haplotype influenced blood pressure in women, whereas 2 angiotensinogen haplotypes were associated in men. We also detected gene-by-gene, gender-specific interactions (epistasis) in pathophysiological pathways. This study reveals gender-specific effects of single nucleotide polymorphisms, haplotypes, and gene-by-gene interactions that determine blood pressure in white Americans. Such genetic variants may define genetically and etiologically distinct subgroups of men and women with essential hypertension and may have implications for rational treatment selection. 相似文献
63.
Wessel J Moratorio G Rao F Mahata M Zhang L Greene W Rana BK Kennedy BP Khandrika S Huang P Lillie EO Shih PA Smith DW Wen G Hamilton BA Ziegler MG Witztum JL Schork NJ Schmid-Schönbein GW O'Connor DT 《Journal of hypertension》2007,25(2):329-343
BACKGROUND: C-reactive protein (CRP) both reflects and participates in inflammation, and its circulating concentration marks cardiovascular risk. Here we sought to understand the role of heredity in determining CRP secretion. METHODS: CRP, as well as multiple facets of the metabolic syndrome, were measured in a series of 229 twins, both monozygotic (MZ) and dizygotic (DZ), to estimate trait heritability (h2). Single nucleotide polymorphism (SNP) genotyping was done at adrenergic pathway loci. Haplotypes were inferred from genotypes by likelihood methods. Association of CRP with hypertension and the metabolic syndrome was studied in a larger series of 732 individuals, including 79 with hypertension. RESULTS: MZ and DZ twin variance components indicated substantial h2 for CRP, at approximately 56 +/- 7% (P < 0.001). CRP was significantly associated (P < 0.05) with multiple features of the metabolic syndrome in twins, including body mass index (BMI), blood pressure (BP), leptin and lipids. In established hypertension, elevated CRP was associated with increased BP, BMI, insulin, HOMA (index of insulin resistance), leptin, triglycerides and norepinephrine. Twin correlations indicated pleiotropy (shared genetic determination) for CRP with BMI (P = 0.0002), leptin (P < 0.001), triglycerides (P = 0.002) and systolic blood pressure (SBP) (P = 0.042). Approximately 9800 genotypes (43 genetic variants at 17 loci) were scored within catecholaminergic pathways: biosynthetic, receptor and signal transduction. Plasma CRP concentration in twins was predicted by polymorphisms at three loci in physiological series within the catecholamine biosynthetic/beta-adrenergic pathway: TH (tyrosine hydroxylase), ADRB1 (beta1-adrenergic receptor) and ADRB2 (beta2-adrenergic receptor). In the TH promoter, common allelic variation accounted for up to approximately 6.6% of CRP inter-individual variance. At ADRB1, variation at Gly389Arg predicted approximately 2.8% of CRP, while ADRB2 promoter variants T-47C and T-20C also contributed. Particular haplotypes and diplotypes at TH and ADRB1 also predicted CRP, though typically no better than single SNPs alone. Epistasis (gene-by-gene interaction) was demonstrated for particular combinations of TH and ADRB2 alleles, consistent with their actions in a pathway in series. In an illustration of pleiotropy, not only CRP but also plasma triglycerides were predicted by polymorphisms at TH (P = 0.0053) and ADRB2 (P = 0.027). CONCLUSIONS: CRP secretion is substantially heritable in humans, demonstrating pleiotropy (shared genetic determination) with other features of the metabolic syndrome, such as BMI, triglycerides or BP. Multiple, common genetic variants in the catecholaminergic/beta-adrenergic pathway contribute to CRP, and these variants (especially at TH and ADRB2) seem to interact (epistasis) to influence the trait. The results uncover novel pathophysiological links between the adrenergic system and inflammation, and suggest new strategies to probe the role and actions of inflammation within this setting. 相似文献
64.
65.
Lars M. Rimol Ingrid Agartz Srdjan Djurovic Andrew A. Brown J. Cooper Roddey Anna K. K?hler Morten Mattingsdal Lavinia Athanasiu Alexander H. Joyner Nicholas J. Schork Eric Halgren Kjetil Sundet Ingrid Melle Anders M. Dale Ole A. Andreassen for the Alzheimer's Disease Neuroimaging Initiative 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(1):384-388
Loss-of-function mutations in the genes associated with primary microcephaly (MCPH) reduce human brain size by about two-thirds, without producing gross abnormalities in brain organization or physiology and leaving other organs largely unaffected [Woods CG, et al. (2005) Am J Hum Genet 76:717–728]. There is also evidence suggesting that MCPH genes have evolved rapidly in primates and humans and have been subjected to selection in recent human evolution [Vallender EJ, et al. (2008) Trends Neurosci 31:637–644]. Here, we show that common variants of MCPH genes account for some of the common variation in brain structure in humans, independently of disease status. We investigated the correlations of SNPs from four MCPH genes with brain morphometry phenotypes obtained with MRI. We found significant, sex-specific associations between common, nonexonic, SNPs of the genes CDK5RAP2, MCPH1, and ASPM, with brain volume or cortical surface area in an ethnically homogenous Norwegian discovery sample (n = 287), including patients with mental illness. The most strongly associated SNP findings were replicated in an independent North American sample (n = 656), which included patients with dementia. These results are consistent with the view that common variation in brain structure is associated with genetic variants located in nonexonic, presumably regulatory, regions. 相似文献
66.
NJ Liptrott M Penny PG Bray J Sathish SH Khoo DJ Back A Owen 《British journal of pharmacology》2009,156(3):497-508
Background and purpose:
The function of transporters in peripheral blood mononuclear cells (PBMC) has been characterized, but less is known about cytochrome P450 (CYP) enzyme function in these cells. Given that cytokines are dysregulated in many diseases, the purpose of this work was to assess the impact of cytokines on the expression of CYPs, transporters and chemokine receptors in PBMC.Experimental approach:
Human PBMC were incubated with cytokines for 48 h. ATP-binding cassette (ABC)B1, ABCC1, ABCC2, CYP2B6, CYP3A4, CXCR4 and CCR5 expression were measured by quantitative polymerase chain reaction and flow cytometry at 0, 4, 8, 24 and 48 h. Enzyme activity was assessed using fluorescent probes.Key results:
We show here functional activity of CYP3A4 and CYP2B6 in PBMC. Furthermore, cytokines had a significant impact on the mRNA and protein expression of all proteins. For example, interleukin-2 (IL-2) had a marked impact on ABCB1 mRNA (% control 4745 ± 11961) and protein (% control 200 ± 57). Increases in drug efflux transporter expression, in response to cytokines, resulted in reduced cellular accumulation of digoxin [decrease of 17% and 26% for IL-2 and interferon-γ (IFNγ) respectively] and saquinavir (decrease of 28% and 30% for IL-2 and IFNγ respectively). The degree to which drug transporter and chemokine receptor expression changed in response to cytokines was positively correlated (e.g. ABCB1 and CXCR4, r2 = 0.545).Conclusions and implications:
These data have important implications for diseases in which cytokines are dysregulated and for which pharmacological intervention targets immune cells. 相似文献67.
Lillie EO Mahata M Khandrika S Rao F Bundey RA Wen G Chen Y Taupenot L Smith DW Mahata SK Ziegler MG Cockburn M Schork NJ O'Connor DT 《Circulation》2007,115(17):2282-2291
68.
Monica N. Starkman David E. Schteingart M.Anthony Schork 《Psychoneuroendocrinology》1992,17(6):619-626
Cushing's Disease is often associated with a depressive syndrome, with mood, vegetative, and cognitive abnormalities of variable severity. In 11 patients with (pituitary ACTH-dependent) Cushing's disease (10 women, 1 man), we studied the relationship between severity of the depressive syndrome and concordance of changes in ACTH and β-lipotropin/β-endorphin (β-LPH/β-E) levels at baseline and in response to metyrapone and dexamethasone. For each condition, blood samples were drawn at 0800h, 1200h, 1600h, and 2200h. Six patients were categorized as mildly depressed (mean[±SD] depressed ood SCORE=0.17±0.4; modified Hamilton Depression scale SCORE=7.6±4.5) and five as severly and five as severely depressed (mean depressed mood SCORE=2.4±0.5; modified Hamilton Depession scale SCORE=15±5.6) (p<0.05). ACTH and β-LPH/β-E were measured by radioimmunoassay. For each experimental condition, changes in levels were scored as concordant if the two peptides moved in parallel between sampling points. There was a relationship between greater severity of depression and more frequent discordant changes in ACTH and β-LPH/β-E levels: The six patients with mild depression exhibited 23 concordant and 3 discordant change patterns, while the five patients with severe depression showed 8 concordant and 15 discordant patterns. The mean percentage of concordant patterns per patient differed significantly between the two groups (mildly DEPRESSED=90.0±16.7; severely DEPRESSED=34.6±8.7 (p<0.001). When each study condition was examined separately, differences in the frequency of concordance between the groups reached significance during the post-metyrapone phase and with 8.0mmg dexamethasone administration. These initial findings, taken together with data in related areas, suggest that greater diversity in regulation and consecretion of ACTH and β-LPH/β-E may occur than is currently suspected. Such diversity may play a role in the relationship between HPA axis dysregulation and mood disorders. 相似文献
69.
D G Hodgkins T G Robins D L Hinkamp M A Schork W H Krebs 《British journal of industrial medicine》1992,49(4):241-248
The relation between lead in air (PbA) and lead in blood (PbB), concentrations was investigated among 44 workers in five major operations in a United States high volume, lead acid battery plant. The study covered a 30 month period in which workers received frequent PbA and PbB determinations, workers remained in a single job, and PbA concentrations averaged below the US Occupational Safety and Health Administration (OSHA) permissible exposure limit of 50 micrograms/m3. In both univariate and multivariable linear regressions, longitudinal analyses averaging PbA concentrations over the 30 month study period appeared superior to cross sectional analyses using only six month PbA averages to model PbB concentrations. The covariate adjusted coefficient (alpha value) for PbA (mu/m3) in models of PbB (micrograms/100 g) was 1.14. This figure is strikingly higher than that reported in previous studies in the lead acid battery industry in all of which PbA concentrations were substantially higher than in the current study. Plausible explanations for the difference in alpha values include non-linearity of the PbA-PbB curve, a higher fraction of large size particulate associated with higher PbA concentrations, survivor bias among workers exposed to higher PbA concentrations, and the cross sectional designs of most previous studies. Despite previously reported problems with the model used by OSHA to predict PbA-PbB relations, the findings of this study are in good agreement with the predictions of that model. 相似文献
70.
Suppression of ventricular arrhythmias by volatile anesthetics in a canine model of chronic myocardial infarction 总被引:4,自引:0,他引:4
N Deutsch C B Hantler A R Tait A Uprichard M A Schork P R Knight 《Anesthesiology》1990,72(6):1012-1021
Ventricular tachycardia likely secondary to a reentrant mechanism may be reliably induced by programmed electrical stimulation in dogs 4-6 days after creating a 2-h experimental, occlusion-reperfusion myocardial infarction. The effects of 1.1 and 1.8 MAC halothane, isoflurane, and enflurane on pacing-induced arrhythmias were studied in this model. The ease of initiation of ventricular tachycardia was measured in both awake and anesthetized dogs (n = 18). Excitation thresholds, conduction times, and refractory periods in both normal and infarcted myocardium were also determined to understand changes in the ease of induction of the arrhythmias secondary to anesthetic exposure. Halothane and enflurane administration suppressed the induction of ventricular tachycardia compared with the unanesthetized control (P less than 0.01 for both). During isoflurane anesthesia, there was a trend that was not statistically significant for pacing-induced ventricular tachycardia to be less frequent than during the conscious state (P = 0.11). Halothane and enflurane prolonged refractory periods in both normal and infarcted myocardium, whereas isoflurane had that effect only in normal myocardium. In addition, halothane and enflurane tended to increase refractory periods more than isoflurane in both regions. Conduction times and excitation thresholds were not altered by anesthetic administration. It is concluded that halothane and enflurane suppress inducible ventricular arrhythmias secondary to a prior myocardial infarction. In addition, the increased efficacy of halothane and enflurane as antiarrhythmic agents compared with isoflurane in this model may be related to their greater prolongation of refractory periods. 相似文献