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911.
Heflin MT Oddone EZ Pieper CF Burchett BM Cohen HJ 《Journal of the American Geriatrics Society》2002,50(10):1651-1658
OBJECTIVES: To identify associations between the type and number of diagnoses and receipt of screening for breast, cervical, and colorectal cancer by older people. DESIGN: Sixth annual follow-up of a community-based survey with 4,162 participants aged 65 and older at baseline in 1986. SETTING: Piedmont area of North Carolina. PARTICIPANTS: Two thousand two hundred twenty-five subjects with a mean age of 79 who responded in 1992. MEASUREMENTS: Self-reported receipt of clinical breast examination, mammography, Papanicolaou (Pap) smear, and fecal occult blood testing (FOBT) within the 2 years before the survey. RESULTS: Hip fracture was associated with lower rates of mammography (odds ratio (OR) = 0.53, 95% confidence interval (CI) = 0.32-0.87) and cognitive impairment with lower rates of FOBT (OR = 0.71, 95% CI = 0.54-0.94). Hypertension was associated with higher rates of breast examination (OR = 1.56, 95% CI = 1.18-2.07), Pap smear (OR = 1.41, 95% CI = 1.09-1.83), and FOBT (OR = 1.37, 95% CI = 1.12-1.66) and a trend toward increasing rates of mammography (OR = 1.28, 95% CI = 0.98-1.69). The presence of three or more comorbid conditions was associated with an increased rate of mammography (OR = 1.35, 95% CI = 1.06-1.71), breast examination (OR = 1.46, 95% CI = 1.12-1.89), and Pap smear (OR = 1.31, 95% CI = 1.04-1.65). CONCLUSIONS: With few exceptions, the presence of comorbid conditions is not associated with a decreased rate of receipt of screening. In fact, hypertension and the presence of a higher number of comorbid conditions are associated with a higher rate of receipt of cancer screening. This finding may be due to an increase in the frequency of office visits increasing the opportunity for cancer screening. 相似文献
912.
Signaling through GP Ib-IX-V activates alpha IIb beta 3 independently of other receptors 总被引:9,自引:5,他引:9
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Platelet adhesion to von Willebrand factor (VWF) activates alpha IIb beta 3, a prerequisite for thrombus formation. However, it is unclear whether the primary VWF receptor, glycoprotein (GP) Ib-IX-V, mediates alpha IIb beta 3 activation directly or through other signaling proteins physically associated with it (eg, FcR gamma-chain), possibly with the contribution of other agonist receptors and of VWF signaling through alpha IIb beta 3. To resolve this question, human and GP Ibalpha transgenic mouse platelets were plated on dimeric VWF A1 domain (dA1VWF), which engages only GP Ib-IX-V, in the presence of inhibitors of other agonist receptors. Platelet adhesion to dA1VWF induced Src kinase-dependent tyrosine phosphorylation of the FcR gamma-chain and the adapter molecule, ADAP, and triggered intracellular Ca(2+) oscillations and alpha IIb beta 3 activation. Inhibition of Ca(2+) oscillations with BAPTA-AM prevented alpha IIb beta 3 activation but not tyrosine phosphorylation. Pharmacologic inhibition of protein kinase C (PKC) or phosphatidylinositol 3-kinase (PI 3-kinase) prevented alpha IIb beta 3 activation but not Ca(2+) oscillations. Inhibition of Src with 2 distinct compounds blocked all responses downstream of GP Ib-IX-V under static or flow conditions. However, dA1VWF-induced responses were reduced only slightly in GP Ibalpha transgenic platelets lacking FcR gamma-chain. These data establish that GP Ib-IX-V itself can signal to activate alpha IIb beta 3, through sequential actions of Src kinases, Ca(2+) oscillations, and PI 3-kinase/PKC. 相似文献
913.
Natural Killer Cell Alloreactivity in Haploidentical Hematopoietic Stem Cell Transplantation 总被引:5,自引:0,他引:5
Ruggeri L Capanni M Mancusi A Perruccio K Burchielli E Martelli MF Velardi A 《International journal of hematology》2005,81(1):13-17
Natural killer (NK) cells are primed to kill by several activating receptors. NK cell killing of autologous cells is prevented because NK cells coexpress inhibitory receptors (killer cell immunoglobulin-like receptors [KIR]) that recognize groups of (self) major histocompatibility complex class I alleles. Because KIRs are clonally distributed, the NK cell population in any individual are constituted of a repertoire with a variety of class I specificities. NK cells in the repertoire mediate alloreactions when the allogeneic targets do not express the class I alleles that block them. After haploidentical hematopoietic transplantation, NK cell-mediated donor-versus-recipient alloresponses reduce the risk of relapse in acute myeloid leukemia patients while improving engraftment and protecting against graft-versus-host disease. High-resolution molecular HLA typing of recipient and donor, positive identification of donor KIR genes, and, in some cases, functional assessment of donor NK clones identify haploidentical donors who are able to mount donor-versus-recipient NK alloreactions. 相似文献
914.
915.
Clinical usefulness of desmopressin for prevention of surgical bleeding in patients with symptomatic heterozygous factor XI deficiency 总被引:1,自引:0,他引:1
Giancarlo Castaman Marco Ruggeri & Francesco Rodeghiero 《British journal of haematology》1996,94(1):168-170
Heterozygous factor XI (FXI) deficiency is sometimes associated with a significant bleeding tendency. Fresh frozen plasma or FXI concentrates are the mainstay of treatment in patients with a clear bleeding history, especially prior to surgery. However, these treatments are not completely free of risk. Furthermore, thrombosis has been reported in patients with FXI deficiency infused with FXI concentrate. No data are available on the possible efficacy of desmopressin in these patients. Two patients with a clear bleeding history associated with FXI deficiency and no additional haemostatic defects agreed to be treated with desmopressin before carpal tunnel surgery and dental extraction. The reduced basal FXI activity and antigen levels slightly increased after infusion, reaching borderline values. No bleeding was observed after surgical procedures. Desmopressin treatment seems a reasonable and useful choice in symptomatic, heterozygous FXI-deficient patients, thus reducing the cost of treatment, the risk of transmission of blood-borne viruses, and of thrombosis. 相似文献
916.
The effect of the phytoestrogen genistein on plasma nitric oxide concentrations,endothelin-1 levels and endothelium dependent vasodilation in postmenopausal women 总被引:18,自引:0,他引:18
Squadrito F Altavilla D Morabito N Crisafulli A D'Anna R Corrado F Ruggeri P Campo GM Calapai G Caputi AP Squadrito G 《Atherosclerosis》2002,163(2):339-347
The phytoestrogen genistein improves endothelial dysfunction in ovariectomized rats through a nitric oxide-dependent mechanism. We investigated whether genistein alters the balance between the nitric oxide products and endothelin-1 and influences endothelium-dependent vasodilation in postmenopausal women. Sixty healthy postmenopausal women were enrolled in the study. A double-blind, placebo controlled, randomized design was employed. After a 4-week stabilization on a standard fat-reduced diet, participants to the study were randomly assigned to receive either genistein (n=30; 54 mg/day) or placebo (n=30). Flow-mediated, endothelium-dependent vasodilation of the brachial artery, plasma nitric oxide breakdown products and endothelin-1 levels were measured at baseline and after 6 months of genistein therapy. The mean baseline level of nitrites/nitrates was 22+/-10 micromol/l and increased to 41+/-10 micromol/ml after 6 months of treatment. The mean baseline plasma endothelin-1 level was 14+/-4 pg/ml and decreased to 7+/-1 pg/ml following 6 months of treatment with genistein. The mean baseline ratio of nitric oxide to endothelin also significantly increased at the end of treatment. Flow-mediated, endothelium-dependent vasodilation of the brachial artery was 3.9+/-0.8 mm at baseline and increased to 4.4+/-0.7 mm after 6 months of treatment. Placebo-treated women showed no changes in plasma nitrites/nitrates, endothelin-1 levels and flow-mediated vasodilation. Genistein therapy improves flow-mediated endothelium dependent vasodilation in healthy postmenopausal women. This improvement may be mediated by a direct effect of genistein on the vascular function and could be the result of an increased ratio of nitric oxide to endothelin. 相似文献
917.
Eugene Z. Oddone Jennifer M. Gierisch Linda L. Sanders Angela Fagerlin Jordan Sparks Felicia McCant Carrie May Maren K. Olsen Laura J. Damschroder 《Journal of general internal medicine》2018,33(9):1487-1494
Background
A large proportion of deaths and chronic illnesses can be attributed to three modifiable risk factors: tobacco use, overweight/obesity, and physical inactivity.Objective
To test whether telephone-based health coaching after completion of a comprehensive health risk assessment (HRA) increases patient activation and enrollment in a prevention program compared to HRA completion alone.Design
Two-arm randomized trial at three sites.Setting
Primary care clinics at Veterans Affairs facilities.Participants
Four hundred seventeen veterans with at least one modifiable risk factor (BMI?≥?30, <?150 min of at least moderate physically activity per week, or current smoker).Intervention
Participants completed an online HRA. Intervention participants received two telephone-delivered health coaching calls at 1 and 4 weeks to collaboratively set goals to enroll in, and attend structured prevention programs designed to reduce modifiable risk factors.Measurements
Primary outcome was enrollment in a structured prevention program by 6 months. Secondary outcomes were Patient Activation Measure (PAM) and Framingham Risk Score (FRS).Results
Most participants were male (85%), white (50%), with a mean age of 56. Participants were eligible, because their BMI was ≥?30 (80%), they were physically inactive (50%), and/or they were current smokers (39%). When compared to HLA only at 6 months, health coaching intervention participants reported higher rates of enrollment in a prevention program, 51 vs 29% (OR?=?2.5; 95% CI: 1.7, 3.9; p?<?0.0001), higher rates of program participation, 40 vs 23% (OR?=?2.3; 95% CI: 1.5, 3.6; p?=?0.0004), and greater improvement in PAM scores, mean difference 2.5 (95% CI: 0.2, 4.7; p?=?0.03), but no change in FRS scores, mean difference 0.7 (95% CI ??0.7, 2.2; p?=?0.33).Conclusions
Brief telephone health coaching after completing an online HRA increased patient activation and increased enrollment in structured prevention programs to improve health behaviors.ClinicalTrials.gov Identifier
NCT01828567918.
Glanzmann thrombasthenia: deficient binding of von Willebrand factor to thrombin-stimulated platelets. 总被引:36,自引:4,他引:36
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Z M Ruggeri R Bader L de Marco 《Proceedings of the National Academy of Sciences of the United States of America》1982,79(19):6038-6041
Glanzmann thrombasthenia is an inherited bleeding disorder characterized by the failure of platelets to aggregate in response to almost all stimuli. However, thrombasthenic platelets will aggregate with bovine and porcine von Willebrand factor (vWF) and will show normal ristocetin-induced binding and aggregation in the presence of human vWF. In contrast, we now report that the specific binding of vWF to the thrombin-stimulated platelets was less than 20% of normal in three patients with Glanzmann thrombasthenia. Analysis of binding isotherms was based on the assumption of one class of binding sites for vWF on the platelet membrane. Double-reciprocal plots were used to calculate maximal binding at saturation and apparent dissociation constant (Kd). In nine normals, 2.82 +/- 0.64 micrograms (+/- SD) of vWF bound to 10(8) platelets at saturation, with Kd (+/- SD) = 3.65 +/- 1.23 micrograms/ml. In two patients with thrombasthenia binding was markedly decreased and did not approach saturation. In the third patient, binding at saturation corresponded to 0.21 micrograms per 10(8) platelets, with Kd = 3.93 micrograms/ml. These findings suggest that mechanisms underlying the vWF-platelet interaction are incompletely reflected in ristocetin-dependent assay systems. Moreover, these results, in addition to those previously reported for fibronectin, suggest that the platelet defect in Glanzmann thrombasthenia is not limited to decreased binding of fibrinogen but involves several glycoproteins that are known to interact with platelets. 相似文献
919.
920.
Inhibition of platelet function with synthetic peptides designed to be high-affinity antagonists of fibrinogen binding to platelets. 总被引:5,自引:2,他引:5
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Z M Ruggeri R A Houghten S R Russell T S Zimmerman 《Proceedings of the National Academy of Sciences of the United States of America》1986,83(15):5708-5712
We have constructed synthetic peptides modeled on the sequences of (i) Arg-Gly-Asp, present in fibrinogen, fibronectin, and von Willebrand factor, and of (ii) the fibrinogen gamma chain (gamma 400-411) His-His-Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val. The concentration of each peptide that inhibits 50% of 125I-labeled fibrinogen binding to thrombin-stimulated platelets (IC50) was then determined. The IC50 for (gamma 400-411) was 48-180 microM at a fibrinogen concentration of 60 micrograms/ml. A substitution of arginine for alanine at position 9 decreased the IC50 to 14.5 microM. Arginine substitutions for all other residues on the amino-terminal side of the peptide Arg9-Gly-Asp-Val resulted in an IC50 of 0.4-0.8 microM, and the IC50 of the peptide Arg13-Gly-Asp-Val was 0.2-0.3 microM. This contrasts with an IC50 of 200 microM for Arg5-Gly-Asp-Val-Arg4 and an IC50 greater than 1 mM for the peptide Arg12. The inhibitory effect resulted primarily in a decreased affinity of fibrinogen binding to platelets, although the number of available binding sites had also decreased. Binding was completely inhibited. At concentrations between 10 and 18 microM, Arg9-Gly-Asp-Val blocked all ADP-induced aggregation in citrated platelet-rich plasma. The peptide Tyr-His-His-Lys-Arg-Lys-Arg-Lys-Gln-Arg-Gly-Asp-Val was labeled with 125I to quantitate its binding to thrombin-stimulated platelets; at saturation, 59,990 molecules were bound per cell (Kd = 3.8 X 10(-7) M). These modified synthetic peptides bind to platelets with the same affinity as does intact fibrinogen and inhibit platelet function. The increased affinity of these modified peptides is greater than 20-fold that of peptides comprised of only native sequences and is a prerequisite for the potential antithrombotic use of these agents. 相似文献