Multi-modular bone healing assessment in a randomized controlled clinical trial of root-end surgery with the use of leukocyte- and platelet-rich fibrin and an occlusive membrane

Clinical Oral Investigations - The aim of this study was to assess in a multi-modular manner the bone healing 1 year post root-end surgery (RES) with leukocyte- and platelet-rich fibrin...     

感知胃灼热和反胃的决定因素

背景与目的：目前尚不清楚为什么有些胃食管反流会引起症状，而有些不会。作者对患者感知胃食管反流的决定因素进行了调查。方法：在抑酸治疗停止后对32例提示有胃食管反流症状的患者进行24h便携式pH值和阻抗监测。对其中至少发生一次反流事件的20例患者，根据有无反流症状进行比较。结果：共监测到1807次反流事件的发生，其中的203次反流伴有症状。与无症状的反流事件相比，有症状的反流与较大的pH值降低幅度（P〈0．001）、低pH值（P〈0．05）和较高的食管近端酸反流程度（P〈0．005）相关。有症状的反流有着较长的容积恢复时间和酸清除时间（P〈0．05和P〈0．002）。在有症状的反流发生之前通常存在一段较长的食管累积酸暴露时间（P〈0．05）。反胃与胃灼热相比，在反胃之前的近端酸反流程度较大；14．8％的症状性反流是弱酸性的。共有426例纯气体反流发生，其中12例伴有症状。与无症状的纯气体反流相比，症状性纯气体反流更多伴随有pH值减少（P〈0．05）。     

Low-dose oral contraceptives and acquired resistance to activated protein C: a randomised cross-over study

This cycle-controlled randomized cross-over study examined the effects of a second-generation oral contraceptive (OC) containing levonorgestrel and a third-generation OC containing desogestrel on the anticoagulant action of activated protein C (APC) in the plasma. The response to APC in plasma was assessed in 28 women who received two consecutive cycles of a second-generation OC (150 mcg levonorgestrel and 30 mcg ethinyl estradiol) or a third-generation OC (150 mcg desogestrel and 30 mcg ethinyl estradiol), and who switched preparations after two pill-free cycles. Normalized APC sensitivity ratio was also taken from these women. Results showed that in the 28 women the normalized APC sensitivity ratio increased during treatment with both preparations. Compared with levonorgestrel, desogestrel-containing OC treatment caused a highly significant (p 0.0001) additional increase in normalized APC sensitivity ratio (0.51; 95% CI, 0.37-0.66). In conclusion, OC treatment diminishes the efficacy with which APC down-regulates in-vitro thrombin formation.     

In vitro comparison of platelet storage in plasma and in four platelet additive solutions,and the effect of pathogen reduction: a proposal for an in vitro rating system

Background The introduction of platelet (PLT) additive solutions (PASs) and pathogen reduction (PR) technologies possibly allow extension of PLT shelf life. It was our aim to compare in vitro quality of leucocyte‐reduced PLT concentrates (PCs) stored in various PASs, including PR, with those in plasma during 8 days of storage. The study was performed in four blood centres where each tested four conditions. Study Design and Methods In paired experiments (n = 12), buffy coat pools were made to which various storage media were added. Plasma served as reference; two centres used InterSol followed by PR (InterSol+PR) and InterSol without PR; T‐sol, SSP+ and Composol were also studied. Results All PCs fulfilled release criteria (pH_37°C > 6·6; swirl present) until Day 8. Marked differences were seen for other parameters, including CD62P expression: 28 ± 5; 31 ± 7; and 39 ± 9% for T‐sol, Intersol+PR and without PR, respectively, which were higher as found for Composol (12 ± 3%), SSP+ (15 ± 5%) and plasma (15 ± 6%). Three parameters (CD62P, Annexin A5, and lactate concentration) were collapsed into one rating value (6 = good quality, 0 = poor quality); PLTs in plasma had a rating of 2·8 ± 1·0, which was higher as for T‐Sol (1·5 ± 0·5), InterSol+PR (1·3 ± 0·6) and without PR (1·7 ± 0·5). PLTs in potassium‐ and magnesium‐containing PASs showed higher ratings as plasma, 4·3 ± 0·5 for Composol and 3·8 ± 0·8 for SSP+. Conclusion PLT concentrates in plasma, SSP+ and Composol scored better using an arbitrary rating system as PLTs stored in T‐Sol or InterSol; PR further impaired rating parameters. The applicability of these differences in rating for clinical effects needs a clinical study.     

Inosine triphosphate pyrophosphatase and thiopurine s-methyltransferase genotypes relationship to azathioprine-induced myelosuppression.

BACKGROUND & AIMS: The use of azathioprine (AZA) in inflammatory bowel disease (IBD) patients is limited by toxicity, which occurs in up to 20% of treated patients. Mutations in the thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) genes have been associated with the occurrence of AZA-related toxicity. The aim of our study was to determine the relative contribution of ITPA and TPMT mutations to the development of toxicity induced by AZA treatment in IBD patients. METHODS: ITPA(94C>A, IVS2+21A>C) and TPMT (238G>C, 460G>A, and 719A>G) genotypes were assessed in 262 IBD patients (159 females, 103 males; 67 patients with ulcerative colitis, 195 patients with Crohn's disease) treated with AZA and were correlated with the development of leukopenia and hepatotoxicity. RESULTS: Leukopenia (leukocyte count, <3.0 x 10(9)/L) was observed in 4.6% of treated patients. The frequencies of mutant ITPA 94C>A and TPMT alleles were significantly higher in the leukopenic population compared with patients without leukopenia (16.7% and 5.4%, respectively, for ITPA 94C>A, and 20.8% and 4%, respectively, for TPMT). Moreover, the ITPA 94C>A and TPMT mutations predicted leukopenia: ITPA 94C>A odds ratio, 3.504; 95% confidence interval, 1.119-10.971 (P = .046); TPMT odds ratio, 6.316; 95% confidence interval, 2.141-18.634 (P = .004). Neither TPMT nor ITPA genotype predicted hepatotoxicity. CONCLUSIONS: ITPA 94C>A and TPMT polymorphisms are associated with AZA-related leukopenia in IBD patients.     

Surveillance history of endoscopically treated patients with early Barrett's neoplasia: nonadherence to the Seattle biopsy protocol leads to sampling error

SUMMARY. The study's aim was to retrospectively evaluate the surveillance history of Barrett's esophagus (BE) patients with endoscopically treated early neoplasia. All BE patients endoscopically treated for early cancer (EC) or high‐grade intraepithelial neoplasia (HGIN) in a lesion or mass between 1998 and 2005 were included. Endoscopy and histology records were reviewed. Ninety‐four patients (78 males, mean age 67 years, 24 HGIN, 70 EC) were included. In 36 (38%) patients, HGIN/EC was diagnosed at (or within 6 months after) initial endoscopy. The remaining 58 (62%) patients had a surveillance history (median duration 7 years, mean 6.7 endoscopies). Seventy‐nine percent of these had low‐grade intraepithelial neoplasia (LGIN) diagnosed at least once during their surveillance period with a median of seven endoscopies and a median number of biopsies that was 50% of what should have been taken according to the Seattle protocol. Patients without any dysplasia during earlier surveillance (n = 12, 21%) had undergone significantly less endoscopies (median four endoscopies, P = 0.02) and had a median biopsy percentage that was 23% of the Seattle protocol (P < 0.001 versus 50% in LGIN). In this selected cohort of patients with early Barrett's neoplasia, 38% of patients were diagnosed at initial endoscopy. Of the patients with a surveillance history, 79% had shown LGIN prior to HGIN/EC diagnosis. Only 21% of patients had a surveillance history without any dysplasia, which in general encompassed endoscopies with an insufficient number of biopsies, suggesting sampling error. This underlines the importance of obtaining an adequate number of biopsies during surveillance endoscopies.     

Effects of storage-induced platelet microparticles on the initiation and propagation phase of blood coagulation

Platelets shed microparticles, which support haemostasis via adherence to the damaged vasculature and by promoting blood coagulation. We investigated mechanisms through which storage-induced microparticles might support blood coagulation. Flow cytometry was used to determine microparticle number, cellular origin and surface expression of tissue factor (TF), procoagulant phosphatidylserine (PtdSer) and glycoprotein (GP) Ib-alpha. The influence of microparticles on initiation and propagation of coagulation were examined in activated factor X (factor Xa; FXa) and thrombin generation assays and compared with that of synthetic phospholipids. About 75% of microparticles were platelet derived and their number significantly increased during storage of platelet concentrates. About 10% of the microparticles expressed functionally active TF, as measured in a FXa generation assay. However, TF-driven thrombin generation was only found in plasma in which tissue factor pathway inhibitor (TFPI) was neutralised, suggesting that microparticle-associated TF in platelet concentrates is of minor importance. Furthermore, 60% of all microparticles expressed PtdSer. In comparison with synthetic procoagulant phospholipids, the maximal rate of thrombin formation in TF-activated plasma was 15-fold higher when platelet-free plasma was titrated with microparticles. This difference could be attributed to the ability of microparticles to propagate thrombin generation by thrombin-activated FXI. Collectively, our findings indicate a role of microparticles in supporting haemostasis by enhancement of the propagation phase of blood coagulation.