Management of failures of first line treatments

Up to 70% of the patients treated to prevent rebleeding will experience a bleeding episode within 2 years. The response should be adapted to the delay after the index bleed, the source and the severity of the haemorrhage, the underlying liver disease and the initial treatment to prevent rebleeding. Bleeding can be caused by endoscopic techniques themselves, which should incitate to complete obliteration rather than to switch to another therapy. Failure of drug therapy can be secondary to ineffectiveness, to a lack of compliance, or to an insufficient dosage. The two latter conditions may be corrected. Whenever a patient rebleeds in spite of optimal treatment, liver transplantation should be considered. When such a procedure is contra-indicated and in patients on the waiting list, a Transjugular intra-hepatic porto-systemic shunt (TIPS) should be performed.     

Microanalysis of Worn Surfaces of Selected Rotating Parts of an Internal Combustion Engine

The present paper analyzes the damage of surfaces at spots of frictional contact, namely, the friction nodes on a camshaft and the connecting rod pins of a crankshaft. The resulting wear of the monitored friction nodes reduces the technical life of the machines, which can lead to the decommissioning of the machine. Wear was assessed by measuring roughness and microhardness and by observing the microstructures of the materials. The results of the experiments show that the rotating parts displayed visible wear on the cams, as well as on the connecting rod pins. The experiments revealed that wear was caused by the heating of the material to a high temperature during the operation of the machine and that there was a gradual cooling and tempering of the material, which led to a reduction in the microhardness of the monitored object. Lower microhardness values can be a cause of greater wear of the monitored objects. When comparing the microhardness of the used and the new camshaft, the hardened layer of the new camshaft from secondary production has a significantly smaller thickness compared to worn cams, which leads to the finding of a different material quality compared to the original parts from primary production. This fact indicates that the wear of a new camshaft as a spare part can contribute to the shortening of the technical life of friction nodes.     

A case of invasive hemolymphangioma of the pancreas

Hemolymphangioma of the pancreas is a very rare benign tumor. There were only five reports of this disease until March 2008. Herein, we report a case of hemolymphangioma of the pancreas with gastrointestinal bleeding due to duodenal invasion. A 53-year-old man had been admitted a referral hospital because of severe anemia due to gastrointestinal bleeding in December 2005. He was then transferred to our institute with a diagnosis of a tumor of the head of the pancreas with duodenal invasion in January 2006. No abnormalities were revealed except for anemia in laboratory data including CEA and CA19-9. Gastrointestinal endoscopy revealed bleeding at the duodenum. Computed tomography also demonstrated a heterogenous mass at the pancreatic head and suspected invasion to the duodenal wall. Ultrasonography showed a huge mass at the pancreatic head with a mixture of high and low echoic areas. Pylorous-preserving pancreatoduodenectomy was performed. The pancreatic tumor was soft and had invaded to the duodenum. The pathological diagnosis was a hemolymphangioma of the pancreas invaded to the duodenum. His postoperative course was uneventful and he was discharged on the 26th d after surgery. Hemolymphangioma of the pancreas is a very rare benign tumor. In a literature review until March 2008, we found five case reports. Major symptoms are abdominal pain and distension due to the enlarged tumor. However, we experienced a case of hemolymphangioma of the pancreas with gastrointestinal bleeding due to invasion to the duodenum. This disease is a very rare entity, but should be considered when patients have gastrointestinal bleeding.     

Development and design of specific inhibitors of angiotensin-converting enzyme

Captopril is a remarkably effective new antihypertensive drug designed and developed as a potent and specific inhibitor of angiotensin-converting enzyme, a zinc metallopeptidase that participates in the synthesis of a hypertensive peptide, angiotensin II, and in the degradation of a hypotensive peptide, bradykinin. Earlier studies with a snake venom peptide (teprotride or SQ 20881) that could be administered only by injection demonstrated that specific inhibitors of angiotensin-converting enzyme could be highly effective as antihypertensive drugs, and helped to clarify the specificity and mechanism of action of the enzyme. A hypothetical model of the active center of angiotensin-converting enzyme based on its presumed analogy to the well characterized zinc metallopeptidase carboxypeptidase A was used to guide logical sequential improvements of a weakly active prototype inhibitor that led eventually to the highly optimized structure of captopril. The hypothetical working model of the active site of angiotensin-converting enzyme used to develop captopril continues to provide a firm basis for development of new types of specific inhibitors of this biologically important enzyme.     

A Case of Endometriosis of the Appendix

A 51-year-old woman visited our clinic her chief complaint being right hypogastric discomfort. An abdominal ultrasonography revealed a circular, cystic mass in the right hypogastric region. A colorectal radiography disclosed a semi-globular shadow defect at the end of the cecum and did not visualize the appendix. A colorectal endoscopy revealed a submucosal tumor accompanied by a central dimple which seemed to represent the ostium appendicis vermiformis. Based on a preoperative diagnosis of submucosal tumor, the patient underwent a partial resection of the cecum. A histopathological examination of tissue removed led to a diagnosis of endometriosis of the appendix. In Japan, 7 cases of endometriosis of the appendix have been reported to date. In those cases, endometriosis of the appendix was detected as a lesion accompanying endometriosis of some other site or during laparotomy was based on a diagnosis of acute appendicitis. Unlike these cases, the patient presented here had been diagnosed by a preoperative colorectal radiography and endoscopy as having a submucosal tumor of the appendix.     

Characterization of a Population of Monozygotic Twins with Asthma

Background. Asthma is a complex inflammatory lung disease that results from allergic and nonallergic environmental exposures in genetically susceptible individuals. The interrelationship and impact of environmental and genetic determinants on the development of asthma is still unclear. Monozygotic twins (MZT) have been considered a potentially useful population to investigate the role of genetic and environmental factors on asthma because of their identical genetic background, similar childhood environmental exposures, and expected high concordance rate for asthma. Methods. A detailed questionnaire designed to obtain demographic information, medical history/severity of asthma, and environmental exposures was distributed to 43 pairs of MZT pairs where one or both probands had a history of asthma. All twin pairs were clinically evaluated for atopy by skin testing. Asthma was assessed by questionnaire, baseline spirometry, disease severity, airway reactivity, and medication scores. Results. Based on a history of physician-diagnosed asthma, disease severity, airway reactivity, and medication scores, 22 MZT pairs were identified as concordant (C) for asthma while 21 MZT pairs were discordant (D) for asthma. Those MZT-C for asthma were on average older and more often female. Adjusted odds ratios for age and gender revealed that MZT-C for asthma had a 2.3 greater likelihood of childhood tobacco exposure and a 1.8 greater likelihood of early exposure to a pet compared to MZT-D pairs. In addition, MZT-C for asthma had a 2.4 greater likelihood of being full term vs. premature at birth. None of these odds ratios were statistically significant due to a small sample size. However, a trend for a greater likelihood of earlier environmental exposures was observed for MZT-C asthma pairs. Among MZT-D probands, a history of asthma in one proband was supported by a lower FEV₁ and higher airway reactivity, disease severity, asthma symptom, and medication scores compared to the nonasthma proband. There was significant intrapair heterogeneity among MZT-C and MZT-D probands in their positive skin test responses to specific aeroallergens. Conclusion. Cross-sectional evaluation of larger MZT populations where one or both proband has asthma with a long-term prospective follow-up may be a feasible way for identifying the impact of environmental determinants as independent risk factors for the development of asthma.     

The experience of being a female carrier of haemophilia and the mother of a haemophilic child

Limited research has been conducted on how the female carrier experiences her life with a haemophilic child, and earlier studies are mostly questionnaire‐based. No previous qualitative study on the female carrier's situation has been conducted in Sweden. The aim of the study was to describe the lived experience of being a carrier of severe or moderate haemophilia and of being the mother of a haemophilic child. The study was conducted via qualitative interviews and analysed by means of a phenomenological hermeneutic method; a total of 13 haemophilia carriers were interviewed in 2010. Being a carrier of haemophilia and having a haemophilic child was life changing. The women moved from a state of sad, guilty chaos to reconciling themselves with the new situation. Our analysis revealed three acts in which phenomena appeared: the time after diagnosis, the turning point and reconciliation with a changing life. Emerging as crucial to the process of reconciliation with a changing life was a sense of being fully informed and supported. The Haemophilia Treatment Centre (HTC) should create an environment that encourages learning, and the team should invite and encourage the woman's partner to be actively involved in the child's care. Moreover, the results indicate that it would be beneficial to invite female carriers to receive patient education at the HTC before they plan to start a family. During this visit, the woman may gain a greater understanding of her carriership to prepare her for future decisions concerning prenatal diagnosis, for example.     

Influence of ambulance crew's length of experience on the outcome of out-of-hospital cardiac arrest.

AIMS: To investigate whether an ambulance crew's length of experience affected the outcome of out-of-hospital cardiac arrest. METHODS AND RESULTS: This was a population-based, retrospective observational study of attempted resuscitations in 1547 consecutive arrests of cardiac aetiology by Nottinghamshire Emergency Ambulance Service crew. One thousand and seventy-one patients were managed by either a paramedic or a technician crew without assistance from other trained individuals at the scene of arrest. Overall, the chances of a patient surviving to be discharged from hospital alive did not appear to be affected by the paramedic's length of experience (among survivors, 18 months experience vs non-survivors 16 months experience, P = 0.347) but there appears to be a trend in the effect of a technician's length of experience on survival (among survivors, 60 months experience vs non-survivors 28 months experience, P = 0.075). However, when a technician had 4 years of experience or more and a paramedic 1 year's experience, survival rates did improve. Logistic regression analysis, adjusted for factors known to influence outcome, revealed that chances of survival increased once technicians had over 4 years of experience after qualification (odds ratio 2.71, 95% CI 1.17 to 6.32, P = 0.02) and paramedics after just 1 year of experience (odds ratio 2.68, 95% CI 1.05 to 6.82, P = 0.04). CONCLUSIONS: Survival from out-of-hospital cardiac arrest varies with the type of ambulance crew and length of experience after qualification. Experience in the field seems important as paramedics achieve better survival rates after just 1 year's experience, while technicians need to have more than 4 years' experience to improve survival.     

Analysis of the environmental impact of insulin infusion sets based on loss of resources with waste

Insulin pump therapy [continuous subcutaneous insulin infusion (CSII)] requires regular change of infusion sets every 2-3 days in order to minimize the risk of skin irritations or other adverse events. This has been discussed to be a potential burden to the environment. The purpose of this analysis was to perform an environmental assessment of insulin pump infusion sets based on loss of resources occurring during incineration of the discarded products and by means of a lifecycle concept used to weight a material in relation to its rareness on earth and its consumption. In addition to five infusion sets (Inset30, InsetII, Comfort, Quick-set, and Cleo), a patch pump (Omnipod) was also included in this analysis. The annual loss in waste of the so called "person reserve" of 3 days of catheter use was compared with daily consumption of a cup of coffee in a disposable paper cup and to a soft drink in an aluminum can. The weight-based loss in resources through waste for the infusion sets (except for Cleo) corresponded to 70-200% of the loss of resources for a coffee cup (Cleo, 320%; Omnipod, 1,821,600%) and to 1-3% of the loss from an aluminum soft drink can (Cleo, 5%; Omnipod, 31,200%). The loss or resources by use of infusion sets used in insulin pump therapy appears to be low and is similar to the burden induced by the uptake of one cup of coffee per day. The loss or resources with regular CSII is considerably lower than the loss or resources induced by patch pumps.     

Behavioral and neural correlates of delay of gratification 40 years later

We examined the neural basis of self-regulation in individuals from a cohort of preschoolers who performed the delay-of-gratification task 4 decades ago. Nearly 60 individuals, now in their mid-forties, were tested on "hot" and "cool" versions of a go/nogo task to assess whether delay of gratification in childhood predicts impulse control abilities and sensitivity to alluring cues (happy faces). Individuals who were less able to delay gratification in preschool and consistently showed low self-control abilities in their twenties and thirties performed more poorly than did high delayers when having to suppress a response to a happy face but not to a neutral or fearful face. This finding suggests that sensitivity to environmental hot cues plays a significant role in individuals' ability to suppress actions toward such stimuli. A subset of these participants (n = 26) underwent functional imaging for the first time to test for biased recruitment of frontostriatal circuitry when required to suppress responses to alluring cues. Whereas the prefrontal cortex differentiated between nogo and go trials to a greater extent in high delayers, the ventral striatum showed exaggerated recruitment in low delayers. Thus, resistance to temptation as measured originally by the delay-of-gratification task is a relatively stable individual difference that predicts reliable biases in frontostriatal circuitries that integrate motivational and control processes.     

Elucidation of the active conformation of cinchona alkaloid catalyst and chemical mechanism of alcoholysis of meso anhydrides

Complementary to enantioselective transformations of planar functionalities, catalytic desymmetrization of meso compounds is another fundamentally important strategy for asymmetric synthesis. However, experimentally established stereochemical models on how a chiral catalyst discriminates between two enantiotopic functional groups in the desymmetrization of a meso substrate are particularly lacking. This article describes our endeavor to elucidate the chemical mechanism and characterization of the active conformation of the cinchona alkaloid-derived catalyst for a desymmetrization of meso cyclic anhydrides via asymmetric alcoholysis. First, our kinetic studies indicate that the cinchona alkaloid-catalyzed alcoholysis proceeds by a general base catalysis mechanism. Furthermore, the active conformer of the cinchona alkaloid-derived catalyst DHQD-PHN was clarified by catalyst conformation studies with a designed, rigid cinchona alkaloid derivative as a probe. These key mechanistic insights enabled us to construct a stereochemical model to rationalize how DHQD-PHN differentiates the two enantiotopic carbonyl groups in the transition state of the asymmetric alcoholysis of meso cyclic anhydrides. This model not only is consistent with the sense of asymmetric induction of the asymmetric alcoholysis but also provides a rationale on how the catalyst tolerates a broad range of cyclic anhydrides. These mechanistic insights further guided us to develop a novel practical catalyst for the enantioselective alcoholysis of meso cyclic anhydrides.     

Critical effect of dependency groups on the function of networks

Current network models assume one type of links to define the relations between the network entities. However, many real networks can only be correctly described using two different types of relations. Connectivity links that enable the nodes to function cooperatively as a network and dependency links that bind the failure of one network element to the failure of other network elements. Here we present an analytical framework for studying the robustness of networks that include both connectivity and dependency links. We show that a synergy exists between the failure of connectivity and dependency links that leads to an iterative process of cascading failures that has a devastating effect on the network stability. We present exact analytical results for the dramatic change in the network behavior when introducing dependency links. For a high density of dependency links, the network disintegrates in a form of a first-order phase transition, whereas for a low density of dependency links, the network disintegrates in a second-order transition. Moreover, opposed to networks containing only connectivity links where a broader degree distribution results in a more robust network, when both types of links are present a broad degree distribution leads to higher vulnerability.     

On the origin of the hierarchy of color names

One of the fundamental problems in cognitive science is how humans categorize the visible color spectrum. The empirical evidence of the existence of universal or recurrent patterns in color naming across cultures is paralleled by the observation that color names begin to be used by individual cultures in a relatively fixed order. The origin of this hierarchy is largely unexplained. Here we resort to multiagent simulations, where a population of individuals, subject to a simple perceptual constraint shared by all humans, namely the human Just Noticeable Difference, categorizes and names colors through a purely cultural negotiation in the form of language games. We found that the time needed for a population to reach consensus on a color name depends on the region of the visible color spectrum. If color spectrum regions are ranked according to this criterion, a hierarchy with [red, (magenta)-red], [violet], [green/yellow], [blue], [orange], and [cyan], appearing in this order, is recovered, featuring an excellent quantitative agreement with the empirical observations of the WCS. Our results demonstrate a clear possible route to the emergence of hierarchical color categories, confirming that the theoretical modeling in this area has now attained the required maturity to make significant contributions to the ongoing debates concerning language universals.     

Influence of spasmolytic analgesics on motility of sphincter of oddi

The effects on the sphincter of Oddi of intravenous administration of dipyrone, 2.5 g; tramadol, 50 mg; indomethacin, 75 mg;N-butylscopolamine, 20 mg; and nitroglycerin, 1 mg, in comparison to physiological saline were assessed in a single-blind study in 36 patients hospitalized with upper abdominal pain. Basal sphincter pressure and sphincter motility were measured for a 5-min period after treatment by endoscopic manometry. Nitroglycerin and dipyrone both caused a significant fall in basal sphincter pressure, whileN-butylscopolamine and nitroglycerin produced a significant decrease in contraction frequency. Therefore, dipyrone, in contrast to tramadol and indomethacin, exhibits spasmolytic activity in addition to analgesia in biliary pain.This study was sponsored by Hoechst AG, Frankfurt/M., Germany     

布鲁氏菌17.3kDa蛋白的表达及其免疫学评价(英文)

目的获得布鲁氏菌保护性抗原17.3kDa重组蛋白并以此构建亚单位疫苗。方法用PET32a(+)原核表达载体表达17.3kDa蛋白纯化后加氟氏佐剂肌肉注射免疫小鼠,三免后测定免疫功能进行免疫效果的评价。结果ELISA、WesternBlot检测到免疫鼠体内有特异性抗体产生,蛋白苗所诱导产生的IgG1抗体远远高于IgG2a;通过细胞因子和CD分子测定表明重组蛋白以诱发ThⅡ型免疫为主。结论所表达的布鲁氏菌17.3kDa蛋白苗具有诱导特异性细胞和体液免疫应答的能力,可作为潜在的布鲁氏菌新型疫苗或诊断抗原,有进一步研究的意义。     

The COPD Comorbidome in the Light of the Degree of Dyspnea and Risk of Exacerbation

The BODE group designed a bubble chart, analogous to the solar system, which depicts the prevalence of each disease and its association with mortality and called it a “comorbidome”. Although this graph was used to represent mortality and, later, the risk of needing hospital admission, it was not applied to visualize the association between a set of comorbidities and the categories of the GOLD 2017 guidelines, neither according to the degree of dyspnea nor to the risk of exacerbation. For the purpose of knowing to which extent each comorbidity associates with each of the two conditions—most symptomatic group (groups B and D) and highest risk of exacerbation (groups C and D)—we performed a analysis based on the comorbidome. 439 patients were included. Cardiovascular comorbidity (especially cardiac and renal disease) is predominantly observed in patients with a higher degree of dyspnea, whereas bronchial asthma and stroke occur more frequently in subjects at higher risk of exacerbation. This is the first time that the comorbidome is presented based on the categories of the GOLD 2017 document, which we hope will serve as a stimulus for scientific debate.     

Evaluation of gastrointestinal bleeding: Update of current radiologic strategies

Gastrointestinal bleeding(GIB) is a common presenta-tion with significant associated morbidity and mortality, the prevalence of which continues to rise with the ever-increasing aging population. Initial evaluation includes an esophagoduodeonscopy and/or colonoscopy, which may fail to reveal a source. Such cases prove to be a dilemma and require collaboration between gastroen-terology and radiology in deciding the most appropriate approach. Recently, there have been a number of ra-diologic advances in the approach to GIB. The purpose of this review is to provide an evidence-based update on the most current radiologic modalities available and an algorithmic approach to GIB.     

The impact of school-based prevention of overweight on psychosocial well-being of children

This review aimed to gain insight in the extent to which psychosocial effects of obesity prevention programmes have been studied, to give an overview of the methods used to measure the particular psychosocial aspects and – if possible – to quantify the effects found. Intervention studies ( n  = 267) covering the period 1990–October 2005 were derived from seven reviews about childhood obesity interventions. An additional search identified 2754 studies covering the period January 2005–February 2008. In total, 2901 papers (excluding 120 duplicates) were screened for inclusion. Sixty-nine papers covering 53 interventions were included and screened on measuring psychosocial variables. All original authors were contacted. Seven of the selected interventions measured psychosocial variables, five of which evaluated a net intervention effect as compared with a control condition. Only two interventions reported a statistically significant net intervention effect (a decrease in use of purging or diet pills and a decrease in peer ratings of aggression and observed verbal aggression). We conclude that a minority of childhood obesity interventions investigate the effects of their programmes on psychosocial well-being of children and adolescents. It is recommended that in the future, these programmes will be evaluated in a uniform way on a broad range of psychosocial aspects     

A review of the quality of randomized clinical trials of adjunctive therapy for the treatment of cerebral malaria

BACKGROUND: Randomized controlled clinical trials (RCTs) of adjunctive treatment to reduce the high-mortality associated with cerebral malaria (CM) have so far failed to show any benefit. This may be due in part to improperly designed and/or conducted trials. Therefore a systematic review of quality of RCTs for the treatment of CM with mortality as either primary or secondary outcome published between 1980 and 2000, was conducted. METHODS: RCTs from the peer-reviewed literature using electronic searches. Methodological quality was assessed using an individual component approach (adequacy of concealment of allocation schedule, generation of allocation sequence, double blinding and analysis of participant as randomized). Sample sizes were recalculated for the ability of reviewed trials to detect 25% and 50% reductions in mortality. RESULTS: Nine trials satisfied the inclusion criteria and were reviewed. Only two had sufficient power to detect a 50% reduction in mortality, and none could detect a 25% reduction. All the trials had inadequate methodological quality in one or more of the components, although in two trials these deficiencies were few. CONCLUSION: There is a need for researchers and donors to ensure proper planning and implementation of RCTs in developing countries. In CM, demonstration of worthwhile reduction in mortality by a single intervention will require a large number of subjects, which a single centre may not be able to recruit.     

Characterization of a Population of Monozygotic Twins with Asthma

Background. Asthma is a complex inflammatory lung disease that results from allergic and nonallergic environmental exposures in genetically susceptible individuals. The interrelationship and impact of environmental and genetic determinants on the development of asthma is still unclear. Monozygotic twins (MZT) have been considered a potentially useful population to investigate the role of genetic and environmental factors on asthma because of their identical genetic background, similar childhood environmental exposures, and expected high concordance rate for asthma. Methods. A detailed questionnaire designed to obtain demographic information, medical history/severity of asthma, and environmental exposures was distributed to 43 pairs of MZT pairs where one or both probands had a history of asthma. All twin pairs were clinically evaluated for atopy by skin testing. Asthma was assessed by questionnaire, baseline spirometry, disease severity, airway reactivity, and medication scores. Results. Based on a history of physician-diagnosed asthma, disease severity, airway reactivity, and medication scores, 22 MZT pairs were identified as concordant (C) for asthma while 21 MZT pairs were discordant (D) for asthma. Those MZT-C for asthma were on average older and more often female. Adjusted odds ratios for age and gender revealed that MZT-C for asthma had a 2.3 greater likelihood of childhood tobacco exposure and a 1.8 greater likelihood of early exposure to a pet compared to MZT-D pairs. In addition, MZT-C for asthma had a 2.4 greater likelihood of being full term vs. premature at birth. None of these odds ratios were statistically significant due to a small sample size. However, a trend for a greater likelihood of earlier environmental exposures was observed for MZT-C asthma pairs. Among MZT-D probands, a history of asthma in one proband was supported by a lower FEV₁ and higher airway reactivity, disease severity, asthma symptom, and medication scores compared to the nonasthma proband. There was significant intrapair heterogeneity among MZT-C and MZT-D probands in their positive skin test responses to specific aeroallergens. Conclusion. Cross-sectional evaluation of larger MZT populations where one or both proband has asthma with a long-term prospective follow-up may be a feasible way for identifying the impact of environmental determinants as independent risk factors for the development of asthma.