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71.
Takuya Takeichi Arti Nanda Lu Liu Amr Salam Patrick Campbell Kenneth Fong Masashi Akiyama Linda Ozoemena Kristina L. Stone Hejab Al‐Ajmi Michael A. Simpson John A. McGrath 《Experimental dermatology》2013,22(12):825-831
Individuals with inherited skin diseases often pose one of the most difficult diagnostic challenges in dermatology. The hunt for the underlying molecular pathology may involve candidate gene screening or linkage analysis, which is usually determined by the initial history, the physical findings and laboratory tests. Recent technical advances in DNA sequencing, however, are shifting the diagnostic paradigm. Notably, next‐generation sequencing allows a more comprehensive approach to diagnosing inherited diseases, with potential savings of both time and money. In the setting of a paediatric dermatology genetics clinic in Kuwait, we therefore performed whole‐exome sequencing on seven individuals without a priori detailed knowledge of the patients’ disorders: from these sequencing data, we diagnosed X‐linked hypohidrotic ectodermal dysplasia (two cases), acrodermatitis enteropathica, recessive erythropoietic protoporphyria (two siblings) and localized recessive dystrophic epidermolysis bullosa (two siblings). All these groups of disorders are clinically and genetically heterogeneous, but the sequencing data proved inherently useful in improving patient care and avoiding unnecessary investigations. Our observations highlight the value of whole‐exome sequencing, in combination with robust bioinformatics analysis, in determining the precise molecular pathology and clinical diagnosis in patients with genetic skin disorders, notably at an early stage in the clinical evaluation of these often complex disorders and thereby support a new paradigm for future diagnostics. 相似文献
72.
W. O. Tobin J. A. Kinsella G. F. Kavanagh J. S. O’Donnell R. A. McGrath D. R. Collins T. Coughlan D. O’Neill B. Egan S. Tierney T. M. Feeley R. P. Murphy Dominick J. H. McCabe 《Journal of neurology》2013,260(2):590-596
The impact of changing antiplatelet therapy on thrombin generation potential in patients with ischaemic cerebrovascular disease (CVD) is unclear. We assessed patients within 4 weeks of TIA or ischaemic stroke (baseline), and then 14 days (14d) and >90 days (90d) after altering antiplatelet therapy. Thrombin generation was assessed in platelet poor plasma. Ninety-one patients were recruited. Twenty-four were initially assessed on no antiplatelet therapy, and then after 14d (N = 23) and 90d (N = 8) on aspirin monotherapy; 52 were assessed on aspirin monotherapy, and after 14 and 90 days on aspirin and dipyridamole combination therapy; 21 patients were assessed on aspirin and after 14 days (N = 21) and 90 days (N = 19) on clopidogrel. Peak thrombin generation and endogenous thrombin potential were reduced at 14 and 90 days (p ≤ 0.04) in the overall cohort. We assessed the impact of individual antiplatelet regimens on thrombin generation parameters to investigate the cause of this effect. Lag time and time-to-peak thrombin generation were unchanged at 14 days, but reduced 90 days after commencing aspirin (p ≤ 0.009). Lag time, peak thrombin generation and endogenous thrombin potential were reduced at both 14 and 90 days after adding dipyridamole to aspirin (p ≤ 0.01). Lag time was reduced 14 days after changing from aspirin to clopidogrel (p = 0.045), but this effect was not maintained at 90 days (p = 0.2). This pilot study did not show any consistent effects of commencing aspirin, or of changing from aspirin to clopidogrel on thrombin generation potential during follow-up. The addition of dipyridamole to aspirin led to a persistent reduction in peak and total thrombin generation ex vivo, and illustrates the diverse, potentially beneficial, newly recognised ‘anti-coagulant’ effects of dipyridamole in ischaemic CVD. 相似文献
73.
Henderikus J. Stam Patricia A. McGrath Ralph I. Brooke Frances Cosier 《The International journal of clinical and experimental hypnosis》2013,61(3):182-191
The Carleton University Responsiveness to Suggestion Scale (CURSS) of Spanos, Radtke, Hodgins, Bertrand 3 and Stam and Spanos, Radtke, Hodgins, Stam, and Bertrand (1983) was individually administered to a sample of 61 facial pain patients. The mean scores on the 3 CURSS suggestibility dimensions were higher than those of the college student norms. As in previous studies using the CURSS, however, objective scores were smaller when experienced involuntariness was taken into account. Observer scores of overt responses were highly related to self-scores of overt responses. The CURSS also proved a good predictor of reductions in clinical pain following a psychologically based treatment program. 相似文献
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An HLA-compatible platelet transfusion was followed by chills, fever, and severe respiratory distress in a multitransfused patient with chronic lymphocytic leukemia. During the previous 7 days the patient had received blood products without incident, including 8 units of red blood cells (RBC), 24 units of pooled random donor platelet concentrates, and five HLA-compatible platelet pheresis products. The patient had no demonstrable RBC, HLA lymphocytotoxic, platelet or granulocyte antibodies. The platelet donor, a multiparous female, had no granulocyte or RBC antibodies but had lymphocytotoxic antibodies against HLA-A2 CREG (cross-reacting group A2, A28, A23, A24) which reacted not with lymphocytes of the patient but with lymphocytes of the donor whose RBC were transfused 24 h prior to the platelet transfusion reaction and whose HLA type is A23, A24; B44, B57. No RBC donors had HLA lymphocytotoxic, granulocyte, or platelet antibodies against the platelet donor. The patient received three subsequent platelet transfusions from the same donor after removal of the antibody-laden plasma with no adverse reaction. These data suggest an interdonor reaction caused by the presence of cells from the RBC donor received by the patient 24 h prior to the transfusion of donor lymphocytotoxic antibody to HLA-A2 CREG antigens. 相似文献
77.
In this study, the effect of exogenous adenosine triphosphate (ATP) on the immature myocardium was evaluated. Isolated working neonatal rabbit hearts were perfused aerobically for 15 min with Krebs-Henseleit buffer (KHB) at 37 degrees C, and then arrested with St. Thomas solution (STS) in group 1 and STS containing 500 mumol/L of ATP in group 2 at 4 degrees to 6 degrees C and maintained at 10 degrees to 14 degrees C for 60 min. Hearts were reperfused with KHB aerobically at 37 degrees C for 15 min. Each heart served as its own control before and after arrest. Systolic function was significantly depressed in group 1 compared with group 2. There was a significant decrease in the peak left ventricular (LV) systolic pressure in group 1 (preischemia mean [PIM] 54 mm Hg to postischemia mean [PoIM] 42 mm Hg, Student's t test p = 0.007) than in group 2 (PIM 66 to PoIM 62 mm Hg, p = 0.5). The LV pulse pressure decreased in group 1 (PIM 72 to PoIM 54 mm Hg, p = 0.02) but not in group 2 (PIM 84 to PoIM 86 mm Hg, p = 0.9) and the rate of rise of LV pressure (dP/dT) in group 2 improved (PIM 5718 to PoIM 6926 mm Hg, p = 0.4) compared with group 1 (PIM 7021 to PoIM 4125 mm Hg, p = 0.008). The PoIM LV flow (LVF) was greater in group 2 than group 1 (LVF group 1 = 2.7 ml/min, group 2 = 4.5 ml/min). Diastolic pressures were not significantly different in the two groups. Our findings suggest that the incorporation of ATP in STS has a significant effect in improving postischemic LV systolic function in neonatal rabbit hearts. 相似文献
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79.
Lord BI; Woolford LB; Wood LM; Czaplewski LG; McCourt M; Hunter MG; Edwards RM 《Blood》1995,85(12):3412-3415
BB-10010 is a genetically engineered variant of human macrophage inflammatory protein-1 alpha with improved solution properties. We show here that it mobilizes stem cells into the peripheral blood. We investigated the mobilizing effects of BB-10010 on the numbers of circulating 8-day spleen colony-forming units (CFU-S8), CFU-S12, and progenitors with marrow repopulating ability (MRA). A single subcutaneous dose of BB-10010 caused a twofold increase in circulating numbers of CFU-S8, CFU-S12, and MRA 30 minutes after dosing. We also investigated the effects of granulocyte colony-stimulating factor (G- CSF) and the combination of G-CSF with BB-10010 on progenitor mobilization. Two days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA progenitors by 25.7-, 19.8-, and 27.7-fold. A single administration of BB-10010 after 2 days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA even further to 38-, 33-, and 100- fold. Splenectomy resulted in increased circulating progenitor numbers but did not change the pattern of mobilization. Two days of treatment with G-CSF then increased circulating CFU-S8, CFU-S12, and MRA by 64-, 69-, and 32-fold. A single BB-10010 administration after G-CSF treatment further increased them to 85-, 117-, and 140-fold, respectively, compared with control. We conclude that BB-10010 causes a rapid increase in the number of circulating hematopoietic progenitors and further enhances the numbers induced by pretreatment with G-CSF. BB- 10010 preferentially mobilized the more primitive progenitors with marrow repopulating activity, releasing four times the number achieved with G-CSF alone. Translated into a clinical setting, this improvement in progenitor cell mobilization may enhance the efficiency of harvest and the quality of grafts for peripheral blood stem cell transplantation. 相似文献
80.
Muhammed Olanrewaju Afolabi Nuala McGrath Umberto D’Alessandro Beate Kampmann Egeruan B Imoukhuede Raffaella M Ravinetto Neal Alexander Heidi J Larson Daniel Chandramohan Kalifa Bojang 《Bulletin of the World Health Organization》2015,93(5):320-328A
ObjectiveTo assess the effectiveness of a multimedia informed consent tool for adults participating in a clinical trial in the Gambia.MethodsAdults eligible for inclusion in a malaria treatment trial (n = 311) were randomized to receive information needed for informed consent using either a multimedia tool (intervention arm) or a standard procedure (control arm). A computerized, audio questionnaire was used to assess participants’ comprehension of informed consent. This was done immediately after consent had been obtained (at day 0) and at subsequent follow-up visits (days 7, 14, 21 and 28). The acceptability and ease of use of the multimedia tool were assessed in focus groups.FindingsOn day 0, the median comprehension score in the intervention arm was 64% compared with 40% in the control arm (P = 0.042). The difference remained significant at all follow-up visits. Poorer comprehension was independently associated with female sex (odds ratio, OR: 0.29; 95% confidence interval, CI: 0.12–0.70) and residing in Jahaly rather than Basse province (OR: 0.33; 95% CI: 0.13–0.82). There was no significant independent association with educational level. The risk that a participant’s comprehension score would drop to half of the initial value was lower in the intervention arm (hazard ratio 0.22, 95% CI: 0.16–0.31). Overall, 70% (42/60) of focus group participants from the intervention arm found the multimedia tool clear and easy to understand.ConclusionA multimedia informed consent tool significantly improved comprehension and retention of consent information by research participants with low levels of literacy. 相似文献