Family history differs between young women with myocardial infarction and ischemic stroke: results from the RATIO case-control study

BackgroundFamily history may help in risk stratification, especially in the young. This study assesses the predictive value of a positive family history of cardiovascular disease for myocardial infarction (MI) and ischemic stroke (IS).Methods/ResultsThe RATIO study case–control study includes women with MI (N = 248), IS (N = 203) and 925 healthy matched controls. Odds ratios (ORs) and 95% confidence intervals (95%CI) were calculated with logistic regression. The risk of MI was almost fourfold increased in women with a family history positive for MI (OR 3.70, 95%CI 2.68–5.10), whereas the risk of IS was, if anything, only slightly elevated (1.25, 0.83–1.87). A family history of stroke (ischemic and hemorrhagic) was associated with a twofold increase in MI risk (2.00, 1.29–3.12), whereas the IS risk was again not clearly associated (1.37, 0.79–2.40).ConclusionsThe predictive value of a family history for cardiovascular disease differs between MI and IS.     

Cystathionine beta-synthase mutants exhibit changes in protein unfolding: conformational analysis of misfolded variants in crude cell extracts

Protein misfolding has been proposed to be a common pathogenic mechanism in many inborn errors of metabolism including cystathionine β-synthase (CBS) deficiency. In this work, we describe the structural properties of nine CBS mutants that represent a common molecular pathology in the CBS gene. Using thermolysin in two proteolytic techniques, we examined conformation of these mutants directly in crude cell extracts after expression in E. coli. Proteolysis with thermolysin under native conditions appeared to be a useful technique even for very unstable mutant proteins, whereas pulse proteolysis in a urea gradient had limited values for the study of the majority of CBS mutants due to their instability. Mutants in the active core had either slightly increased unfolding (p.A114V, p.E302K and p.G307S) or extensive unfolding with decreased stability (p.H65R, p.T191M, p.I278T and p.R369C). The extent of the unfolding inversely correlated with the previously determined degree of tetrameric assembly and with the catalytic activity. In contrast, mutants bearing aminoacid substitutions in the C-terminal regulatory domain (p.R439Q and p.D444N) had increased global stability with decreased flexibility. This study shows that proteolytic techniques can reveal conformational abnormalities even for CBS mutants that have activity and/or a degree of assembly similar to the wild-type enzyme. We present here a methodological strategy that may be used in cell lysates to evaluate properties of proteins that tend to misfold and aggregate and that may be important for conformational studies of disease-causing mutations in the field of inborn errors of metabolism.     

High VWF, low ADAMTS13, and oral contraceptives increase the risk of ischemic stroke and myocardial infarction in young women

VWF and ADAMTS13 are major determinants of platelet adhesion after vessel injury. In the present study, we aimed to determine whether VWF or ADAMTS13 plasma antigen levels influence the risks of ischemic stroke (IS) or myocardial infarction (MI) in young women and how these risks are affected by oral contraceptive (OC) use. VWF and ADAMTS13 plasma antigen levels were measured in a frequency-matched case-control study of 1018 young (18-49 years) women including 175 IS patients and 205 MI patients. Increasing levels of VWF and decreasing levels of ADAMTS13 were associated with the risk of IS and MI in a dose-dependent manner. Having both high VWF and low ADAMTS13 resulted in an odds ratio (OR) of 6.9 (95% confidence interval [95% CI], 2.0-23.0) for IS and 11.3 (95% CI, 3.6-35.2) for MI. Use of OCs increased the risk of IS and MI associated with high VWF (OR = 12; 95% CI, 5.5-26.2 and OR = 7.5, 95% CI, 3.6-15.7, respectively) and the risk of IS associated with low ADAMTS13 (OR = 5.8, 95% CI, 2.7-12.4). We conclude that high VWF and low ADAMTS13 plasma levels both increase the risk of IS and MI. The risks associated with high VWF or low ADAMTS13 levels are further increased by the use of OCs.     

Aneurysm Treatment <24 Versus 24–72 h After Subarachnoid Hemorrhage

Introduction

In patients with aneurysmal subarachnoid hemorrhage (aSAH), it is unclear whether aneurysm treatment <24 h after ictus results in better outcomes than treatment 24–72 h after aSAH. We studied whether aneurysm occlusion <24 h is associated with better outcomes than occlusion 24–72 h after aSAH.

Methods

We used two cohorts of patients with aSAH: (1) the UMC Utrecht cohort with patients admitted between 2008 and 2012 and (2) the International Subarachnoid Aneurysm Trial cohort. Aneurysm treatment was categorized into <24 h and 24–72 h after ictus. We calculated adjusted risk ratios (aRRs) with 95 % confidence intervals (CIs) using Poisson regression analyses for poor functional outcome (death or dependency) for both cohorts separately, and performed a pooled analysis based on individual patient data. We also performed a worst-case scenario analysis wherein all patients with rebleeding >3 h after admission were re-categorized into the group with aneurysm treatment 24–72 h after aSAH.

Results

We included 1,238 patients (UMC Utrecht cohort: n = 330; ISAT: n = 908). The aRR for poor outcome after treatment <24 h was in the UMC Utrecht cohort 1.84 (95 % CI: 1.25-2.70), in ISAT 1.14 (95 % CI 0.84–1.55), in the pooled analysis 1.37 (95 % CI 1.11–1.68), and in the worst-case scenario pooled analysis 1.24 (95 % CI 1.01–1.52).

Conclusion

Our results suggest that aneurysm occlusion can be performed in day time within 72 h after ictus, instead of on an emergency basis. However, due to the retrospective, non-randomized design of our study, our results cannot be considered as definitive evidence.     

Phenalenone-type phytoalexins mediate resistance of banana plants (Musa spp.) to the burrowing nematode Radopholus similis

The global yield of bananas—one of the most important food crops—is severely hampered by parasites, such as nematodes, which cause yield losses up to 75%. Plant–nematode interactions of two banana cultivars differing in susceptibility to Radopholus similis were investigated by combining the conventional and spatially resolved analytical techniques ¹H NMR spectroscopy, matrix-free UV-laser desorption/ionization mass spectrometric imaging, and Raman microspectroscopy. This innovative combination of analytical techniques was applied to isolate, identify, and locate the banana-specific type of phytoalexins, phenylphenalenones, in the R. similis-caused lesions of the plants. The striking antinematode activity of the phenylphenalenone anigorufone, its ingestion by the nematode, and its subsequent localization in lipid droplets within the nematode is reported. The importance of varying local concentrations of these specialized metabolites in infected plant tissues, their involvement in the plant’s defense system, and derived strategies for improving banana resistance are highlighted.Bananas and plantains (Musa spp.) are among the world’s most important food and cash crops, with a global production of about 138 million tons in 2010. These crops are part of a well-balanced human diet and are a major food staple for more than 400 million people in the tropics (1, 2). About 82% of the world’s banana production is consumed locally, particularly in India, China, and many African countries (Table S1) (1, 2). Export of bananas to the northern hemisphere represents an important source of employment in countries such as Costa Rica, Ecuador, Colombia, and the Philippines (Table S2) (1, 2). Banana yields are severely hampered by fungi, insects, and plant-parasitic nematodes. The burrowing nematode, Radopholus similis (Cobb, 1893) Thorne, 1949, is the key nematode pathogen, causing yield losses up to 75% (3). R. similis is found in all major banana-producing regions of the world; its best-known hosts are bananas, black pepper, Citrus spp. (4), and coffee (5). R. similis causes extensive root lesions that can lead to toppling of banana plants (6).Plant-parasitic nematodes have been effectively managed through the use of nematicides. However, their high toxicity has adverse effects on humans and their toxic residues are known to accumulate through nontarget organisms in the food chain (7). After the withdrawal of many effective nematicides, such as methyl bromide, from the market (8), organophosphate and carbamate nematicides are still intensively applied to banana and therefore continue to threaten the health of agricultural workers and the environment (9). Although several biological control approaches, including the application of both single and multiple control organisms—such as Fusarium oxysporum, Paecilomyces lilacinus, Trichoderma atroviride isolates, and Bacillus firmus—have proved promising under greenhouse conditions, the control they confer to banana plants most probably does not protect plants for more than one cycle in the field, and most of these organisms have yet to be tested under field conditions (10).The in-depth investigation of the plant–nematode interactions at the cellular and molecular level could lead to the development of more rational and efficient control strategies (11). The production of toxic, herbivore-deterrent or -repellent secondary metabolites, which is typical for many plant defense systems, is particularly interesting in this context. Musa cultivars resistant to R. similis have been identified, especially the cultivar Yangambi km5 (Ykm5) (12). Histochemical and ultrastructural investigations of lesions caused by R. similis in Ykm5 revealed the accumulation of phenolic compounds in response to infection (13). Unfortunately, many of these studies were based solely on histochemical staining methods and did not identify the chemical structures of nematicidal secondary metabolites (7, 14, 15). Initial phytochemical analyses of R. similis-infected roots of the Musa cultivar Pisang sipulu identified the phenylphenalenone anigorufone (1) as a phytoalexin produced in response to nematode damage and confirmed earlier suggestions of the significant role of phytoalexins in the plant defense system (16). Phenylphenalenones are a group of special phenylpropanoid-derived natural products (17), which are known as Musaceae phytoalexins (18). The activity of phenylalanine ammonia lyase (EC 4.3.15), the entry-point enzyme of the phenylpropanoid pathway, is correlated to the biosynthesis of specific phenylpropanoids involved in defense and was substantially induced in nematode infected roots of Ykm5 (19). Phenylphenalenone-related compounds show biological activity against bacteria, fungi, algae, and diatoms (18, 20–22). The formation of these compounds has been elicited in banana leaves by Mycosphaerella fijiensis (Black Sigatoka leaf streak disease), in the fruit peels by Colletotrichum musae (anthracnose disease), and in roots and rhizomes by F. oxysporum f. sp. cubense (Panama disease) and R. similis (16, 18, 21, 23).     

Comparison of the performance of the different classification criteria for primary Sjögren’s syndrome: a prospective cohort study

The objective of the study is to compare the longitudinal performance of different classification criteria for primary Sjögren’s syndrome (SS) in a cohort of patients previously diagnosed with primary SS. In each patient, we repeated diagnostic tests as required by the Copenhagen, European, Californian, and American-European Consensus Group (AECG) or the new American College of Rheumatology (ACR) classification criteria. Sixty-three out of 90 eligible patients (70 %) consented to participate. During the follow-up (mean (standard deviation, SD) 7.6 years (0.5)), we observed evolution from primary SS to SS with another systemic autoimmune disease (SAD) in 9/63 (14 %) patients, on average after 4.0 years (SD 0.9). The evolution from primary SS to SS-SADs was significantly more common if the diagnosis of primary SS was initially made using AECG (17 %, p?=?0.008) or ACR (16 %, p?=?0.016) criteria. In the 34 patients who underwent a full diagnostic reassessment, the diagnosis retention rate was statistically significant for all the criteria, except the European criteria. At reassessment, 3/32 (9 %) patients initially diagnosed as having primary SS using the European criteria could not be classified as having primary SS by any of the criteria. The differences in classification when using the AECG and the new ACR criteria were not statistically significant. The longitudinal diagnosis retention rate was highest for the Californian and AECG criteria. Regardless of the classification criteria, some patients eventually develop another SAD.     

Morphological,immunohistochemical and molecular features of inflammatory bowel disease associated colorectal carcinoma and associated mucosal lesions – Single institution experience

Background

Patients with inflammatory bowel disease (IBD) – ulcerative colitis (UC) and Crohn’s disease (CD) have an elevated risk of developing colorectal carcinoma (CRC). Major risk factor in IBD patients is the continuous chronic inflammation leading to development of dysplasia and carcinoma. Nevertheless, other types of non-conventional but suspicious mucosal changes serrated change/dysplasia, NOS and villous hypermucinous change, have also been reported in IBD patients. Preneoplastic potential of these lesions is still not well elucidated.

快速康复外科在腹腔镜胆总管探查取石术中的应用

目的：探讨快速康复外科理念在腹腔镜胆总管探查取石术（LCBDE）中的应用价值。
方法：对60例择期行LCBDE患者,采用快速康复外科理念指导下的围术期处理方法（n=28）和传统的围术期处理方法（n=32）,比较两组术后下床活动时间、进食时间、排气排便时间、住院天数及住院费用、并发症的差异。
结果：快速康复外科组术后进食时间、排便排气时间、下床活动时间、住院天数明显缩短、住院费用明显减少（P<0.05）,两组术后并发症比较差异无统计学意义（P>0.05）。
结论：快速康复外科理念在LCBDE患者中的应用安全、经济、有效,具有较高的临床应用价值。

     

甲状腺癌的外科治疗：附487例报告

目的探讨甲状腺癌的诊断、治疗以及手术并发症的防治等。方法对1990年3月—2006年7月收治的487例甲状腺癌手术治疗的临床资料进行回顾性分析。结果术前和术中诊断甲状腺癌分别为279例(57.3%)和162例(33.3%),术后确诊46例(9.4%);再次手术140例(28.7%),发现残癌79例(56.4%);487例手术患者无1例院内死亡,17例术后出现短暂性声嘶,2例永久性声嘶,14例出现低钙抽搐或肢端麻木。413例患者获随访,其中颈部淋巴结复发者33例,局部复发者24例,远处转移者17例。分化型甲状腺癌,髓样癌和未分化癌术后5年生存率分别为99.8%,95.8%和87.0%。结论甲状腺结节伴钙化者应怀疑甲状腺癌可能,术中冷冻快速切片有助于甲状腺癌的诊断和术式的选择。应充分重视首次手术,术中应常规显露喉返神经。术后患者坚持终生服用甲状腺素片有助于预防复发和转移。