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61.
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Bomprezzi R Schafer R Reese V Misra A Vollmer TL Kala M 《Scandinavian journal of immunology》2011,74(3):219-226
Glatiramer acetate (GA) is an immunomodulatory drug approved for the treatment of clinically isolated syndrome (CIS) and relapsing/remitting multiple sclerosis (RRMS). As an antigen-based therapy, GA induces GA-specific antibodies in treated patients and animals. GA-specific antibodies do not neutralize therapeutic effects on relapses and disability. Rather, it has been suggested that GA-specific antibodies may be associated with improved clinical outcomes. We evaluated antibody responses in eight patients with RRMS treated with GA for 15 months and antibody responses in GA-treated C57BL/6 mice before and after induction of experimental autoimmune encephalomyelitis (EAE). There were no significant differences from pretreatment levels of total IgE or GA-specific IgE in patients with RRMS. Total IgG1, IgG3 and GA-specific IgG4 were significantly increased at 15 months of GA treatment. Antibody type and titre were not associated with clinical outcomes, i.e. expanded disability status scale (EDSS) score, disease burden on magnetic resonance images (MRI) or clinical relapses. In contrast, mice with EAE showed a marked increase in GA-specific IgE and GA-specific IgG1 antibody responses. GA-treated mice demonstrated improved clinical symptoms and lower mortality than untreated controls. Our results suggest that antibody responses to GA are heterogeneous among patients with RRMS, with no apparent association between antibody response and clinical outcomes. Clinical improvements in EAE-induced GA-treated mice suggest that GA-specific IgE and IgG1 may contribute to GA treatment effects in EAE. 相似文献
63.
Alcohol dehydrogenase genetic polymorphisms, low-to-moderate alcohol consumption, and risk of breast cancer 总被引:2,自引:0,他引:2
Visvanathan K Crum RM Strickland PT You X Ruczinski I Berndt SI Alberg AJ Hoffman SC Comstock GW Bell DA Helzlsouer KJ 《Alcoholism, clinical and experimental research》2007,31(3):467-476
BACKGROUND: In vitro, human isoenzymes encoded by genes homozygous for the ADH1C*1 or ADH1B*2 alleles metabolize ethanol to acetaldehyde at a faster rate than those homozygous for the ADH1C*2 or ADH1B*1 allele. Because alcohol is a known risk factor for breast cancer, we evaluated the joint association of genetic variants in ADH and alcohol consumption in relation to breast cancer. METHODS: A nested case-control study of 321 cases and matched controls was conducted. Five single nucleotide polymorphisms (SNPs) in the ADH1C and ADH1B genes were genotyped. Logistic regression was used to assess odds ratios (ORs) and 95% confidence limits (CIs) for each SNP. Haplotype analysis of all 5 SNPs was also undertaken. RESULTS: Among drinkers, the median intake of total alcohol was 13 g/wk (10th-90th percentiles; 4.5-135.9) in cases and 18 g/wk (10th-90th percentiles; 4.5-104.1) in controls. Women who drank alcohol tended to be at an increased risk of developing breast cancer compared with those who did not drink (OR=1.40%, 95% CI 0.97-2.03), particularly those who were premenopausal at the time of breast cancer diagnosis (OR=2.69%, 95% CI: 1.00-7.26). Of the known functional alleles, breast cancer risk was not significantly increased among carriers of at least 1 ADH1C*1 or ADH1B*2 allele, when compared with those homozygous for the genotype at each locus. However, breast cancer risk tended to be lower among women who inherited the G allele at ADH1B IVS1+896A>G (OR=0.62, 95% CI 0.37-1.04). Overall haplotype frequencies were not significantly different between cases and controls. CONCLUSIONS: In this study low levels of alcohol are associated with a modest increase in breast cancer risk that is not altered by known functional allelic variants of the ADH1B and 1C gene. The protective association conferred by the G allele at ADH1B IVS1+896A>G needs further evaluation. 相似文献
64.
Woods K Douketis JD Kathirgamanathan K Yi Q Crowther MA 《Journal of thrombosis and thrombolysis》2007,24(2):93-97
Background In patients who require warfarin interruption before surgery and have an elevated international normalized ratio (INR) before
surgery, low-dose vitamin K may normalize the INR in time for surgery.
Patients and methods In a retrospective cohort study, we assessed the efficacy of 1 mg oral vitamin K to normalize the INR for surgery and whether
resistance to re-anticoagulation occurs when warfarin is restarted after surgery. We studied a cohort of patients with an
INR 1.4–1.9 on the day before surgery who received 1 mg oral vitamin K (vitamin K group), and a comparator group of patients
with a normal INR (≤1.3) on the day before surgery who did not receive vitamin K (no vitamin K group). In both patient groups,
we determined the proportion of patients with a normalized INR on the day of surgery and compared the mean INR after surgery
when warfarin was resumed.
Results Of 43 patients in the vitamin K group, the INR was normalized (≤1.3) in 33 patients (76.6; 95% confidence interval [CI]: 64.1–89.4),
and the INR was normal or near-normal (≤1.4) in 39 patients (90.7; 95% CI: 82.0–99.4) on the day of surgery. The mean (standard
deviation) INR in the vitamin K and no vitamin K group 4–8 days after surgery was 1.75 (0.34) and 1.59 (0.36), respectively
(P = 0.56).
Conclusions In patients requiring interruption of warfarin for surgery, 1 mg oral vitamin K on the day before surgery can normalize the
INR by the day of surgery and may not confer resistance to warfarin re-anticoagulation after surgery. 相似文献
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Marian Branny MD PhD Pavel Osmancik MD PhD Petr Kala MD PhD Martin Poloczek MD Dalibor Herman MD PhD Petr Neuzil MD CSc Pavel Hala MD Milos Taborsky MD CSc Josef Stasek MD PhD Ludek Haman MD PhD Jan Chovancik MD Pavel Cervinka MD PhD Jiri Holy MD Tomas Kovarnik MD PhD David Zemanek MD PhD Stepan Havranek MD PhD Vlastimil Vancura MD PhD Petr Peichl MD PhD Petr Tousek MD PhD Marek Hozman MD Veronika Lekesova MD Jiri Jarkovsky RNDr PhD Martina Novackova Mgr. Klara Benesova Mgr Petr Widimsky MD DrSc Vivek Y. Reddy MD the PRAGUE- Trial Investigators 《Journal of cardiovascular electrophysiology》2023,34(9):1885-1895
Introduction
Observational studies have shown low bleeding rates in patients with atrial fibrillation (AF) treated by left atrial appendage closure (LAAC); however, data from randomized studies are lacking. This study compared bleeding events among patients with AF treated by LAAC and nonvitamin K anticoagulants (NOAC).Methods
The Prague-17 trial was a prospective, multicenter, randomized trial that compared LAAC to NOAC in high-risk AF patients. The primary endpoint was a composite of a cardioembolic event, cardiovascular death, and major and clinically relevant nonmajor bleeding (CRNMB) defined according to the International Society on Thrombosis and Hemostasis (ISTH).Results
The trial enrolled 402 patients (201 per arm), and the median follow-up was 3.5 (IQR 2.6–4.2) years. Bleeding occurred in 24 patients (29 events) and 32 patients (40 events) in the LAAC and NOAC groups, respectively. Six of the LAAC bleeding events were procedure/device-related. In the primary intention-to-treat analysis, LAAC was associated with similar rates of ISTH major or CRNMB (sHR 0.75, 95% CI 0.44–1.27, p = 0.28), but with a reduction in nonprocedural major or CRNMB (sHR 0.55, 95% CI 0.31–0.97, p = 0.039). This reduction for nonprocedural bleeding with LAAC was mainly driven by a reduced rate of CRNMB (sHR for major bleeding 0.69, 95% CI 0.34–1.39, p = .30; sHR for CRNMB 0.43, 95% CI 0.18–1.03, p = 0.059). History of bleeding was a predictor of bleeding during follow-up. Gastrointestinal bleeding was the most common bleeding site in both groups.Conclusion
During the 4-year follow-up, LAAC was associated with less nonprocedural bleeding. The reduction is mainly driven by a decrease in CRNMB. 相似文献68.
Malairajan P Gopalakrishnan G Narasimhan S Veni KJ Kavimani S 《Journal of ethnopharmacology》2007,110(2):348-351
The ethanol extract of Toona ciliata Roemer (heart wood) was evaluated for its anti-ulcer activity against aspirin plus pylorous ligation induced gastric ulcer (antisecretory), HCl-ethanol induced ulcer (cytoprotective) and water immersion stress induced ulcer in rats. We found that Toona ciliata extract at a dose of 300mg/kg p.o. markedly decrease the incidence of ulcers in all the three models. Ethanol extract of Toona ciliata showed significant reduction in gastric volume, free acidity, total acidity and ulcer index. The plant extract also showed gastro protective activity (52.94%), whereas standard drug sucralfate showed 94.85%. Toona ciliata extract showed protection index 43.0% in water immersion stress induced ulcer, whereas standard drug omeprazole showed protection index 100%. 相似文献
69.
Gallicchio L Visvanathan K Burke A Hoffman SC Helzlsouer KJ 《International journal of cancer. Journal international du cancer》2007,121(1):211-215
The objective of this study was to examine the association between nonsteroidal anti-inflammatory drug (NSAID) use and the development of breast cancer, and to assess whether this association differed by estrogen receptor (ER) subtype. Data were analyzed from 15,651 women participating in CLUE II, a cohort study initiated in 1989 in Washington County, MD. Medication data were collected at baseline in 1989 and in 1996. Incident cases of invasive breast cancer occurring from baseline to March 27, 2006 were identified through linkage of cohort participants with the Washington County Cancer Registry and the Maryland State Cancer Registry. Cox proportional hazards modeling was used to calculate the risk ratios (RR) and 95% confidence intervals (95% CI) for breast cancer associated with medication use. Among women in the CLUE II cohort, 418 invasive breast cancer cases were identified during the follow-up period. The results showed that self-reported use of NSAIDs in both 1989 and in 1996 was associated with a 50% reduction in the risk of developing invasive breast cancer compared with no NSAID use in either 1989 or 1996 (RR = 0.50; 95% CI 0.28, 0.91). The protective association between NSAID use and the risk of developing breast cancer was consistent among ER-positive and ER-negative breast cancers, although only the RR for ER-positive breast cancer was statistically significant. Overall, findings from this study indicate that NSAID use is associated with a decrease in breast cancer risk and that the reduction in risk is similar for ER-positive and ER-negative tumors. 相似文献
70.