Multiple cerebral infarction and paradoxical air embolism during hepatectomy using the Cavitron Ultrasonic Surgical Aspirator -A case report-

A venous air embolism and paradoxical air embolism (PAE) are serious complications in patients undergoing a hepatectomy. We report a case of PAE and cerebral infarctions in a patient undergoing a hepatic resection using a Cavitron Ultrasonic Surgical Aspirator (CUSA®). A 65-year-old woman underwent a left lobe hepatectomy. During the middle phase of the liver resection with CUSA®, there was a sudden decrease in arterial blood pressure, end-tidal carbon dioxide and SpO2. With resuscitation, intraoperative ultrasonography revealed massive air emboli in both her left and right heart, which lasted for 40 min. The hepatectomy was completed after the disappearance of the air emboli from her heart. After surgery, her mental status was stuporous. The brain CT and MRI revealed multiple acute cerebral infarctions. Finally, she died from septic shock. This case highlights the need for anesthetists and surgeons to be aware of the potential for CUSA®-related massive PAE

Conservative management for postprostatectomy urinary incontinence

BACKGROUND: Urinary incontinence is common after radical prostatectomy and can also occur in some circumstances after transurethral resection of the prostate (TURP). Conservative management includes pelvic floor muscle training with or without biofeedback, electrical stimulation, extra-corporeal magnetic innervation (ExMI), compression devices (penile clamps), lifestyle changes, or a combination of methods.   OBJECTIVES: To determine the effectiveness of conservative management for urinary incontinence up to 12 months after transurethral, suprapubic, laparoscopic, radical retropubic or perineal prostatectomy, including any single conservative therapy or any combination of conservative therapies.  SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Register (5 February 2014), CENTRAL (2014, Issue 1), EMBASE (January 2010 to Week 3 2014), CINAHL (January 1982 to 18 January 2014), ClinicalTrials.gov and World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (both searched 29 January 2014), and the reference lists of relevant articles.  SELECTION CRITERIA: Randomised or quasi-randomised controlled trials evaluating conservative interventions for urinary continence in men after prostatectomy.  DATA COLLECTION AND ANALYSIS: Two or more review authors assessed the methodological quality of the trials and abstracted data. We tried to contact several authors of included studies to obtain extra information.  MAIN RESULTS: Fifty trials met the inclusion criteria, 45 in men after radical prostatectomy, four trials after TURP and one trial after either operation. The trials included 4717 men of whom 2736 had an active conservative intervention. There was considerable variation in the interventions, populations and outcome measures. Data were not available for many of the pre-stated outcomes. Men's symptoms improved over time irrespective of management.There was no evidence from eight trials that pelvic floor muscle training with or without biofeedback was better than control for men who had urinary incontinence up to 12 months after radical prostatectomy; the quality of the evidence was judged to be moderate (for example 57% with urinary incontinence in the intervention group versus 62% in the control group, risk ratio (RR) for incontinence after 12 months 0.85, 95% confidence interval (CI) 0.60 to 1.22). One large multi-centre trial of one-to-one therapy showed no difference in any urinary or quality of life outcome measures and had narrow CIs. It seems unlikely that men benefit from one-to-one PFMT therapy after TURP. Individual small trials provided data to suggest that electrical stimulation, external magnetic innervation, or combinations of treatments might be beneficial but the evidence was limited. Amongst trials of conservative treatment for all men after radical prostatectomy, aimed at both treatment and prevention, there was moderate evidence of an overall benefit from pelvic floor muscle training versus control management in terms of reduction of urinary incontinence (for example 10% with urinary incontinence after one year in the intervention groups versus 32% in the control groups, RR for urinary incontinence 0.32, 95% CI 0.20 to 0.51). However, this finding was not supported by other data from pad tests. The findings should be treated with caution because the risk of bias assessment showed methodological limitations. Men in one trial were more satisfied with one type of external compression device, which had the lowest urine loss, compared to two others or no treatment. The effect of other conservative interventions such as lifestyle changes remained undetermined as no trials involving these interventions were identified.  AUTHORS' CONCLUSIONS: The value of the various approaches to conservative management of postprostatectomy incontinence after radical prostatectomy remains uncertain. The evidence is conflicting and therefore rigorous, adequately powered randomised controlled trials (RCTs) which abide by the principles and recommendations of the CONSORT statement are still needed to obtain a definitive answer. The trials should be robustly designed to answer specific well constructed research questions and include outcomes which are important from the patient's perspective in decision making and are also relevant to the healthcare professionals. Long-term incontinence may be managed by an external penile clamp, but there are safety problems

Discovery of (R)-2-Amino-6-borono-2-(2-(piperidin-1-yl)ethyl)hexanoic Acid and Congeners As Highly Potent Inhibitors of Human Arginases I and II for Treatment of Myocardial Reperfusion Injury

Recent efforts to identify treatments for myocardial ischemia reperfusion injury have resulted in the discovery of a novel series of highly potent α,α-disubstituted amino acid-based arginase inhibitors. The lead candidate, (R)-2-amino-6-borono-2-(2-(piperidin-1-yl)ethyl)hexanoic acid, compound 9, inhibits human arginases I and II with IC50s of 223 and 509 nM, respectively, and is active in a recombinant cellular assay overexpressing human arginase I (CHO cells). It is 28% orally bioavailable and significantly reduces the infarct size in a rat model of myocardial ischemia/reperfusion injury. Herein, we report the design, synthesis, and structure−activity relationships (SAR) for this novel series of inhibitors along with pharmacokinetic and in vivo efficacy data for compound 9 and X-ray crystallography data for selected lead compounds cocrystallized with arginases I and II.Fil: Van Zandt, Michael C.. Institutes for Pharmaceutical Discovery; Estados UnidosFil: Whitehouse, Darren L.. Institutes for Pharmaceutical Discovery; Estados UnidosFil: Golebiowski, Adam. Institutes for Pharmaceutical Discovery; Estados UnidosFil: Ji, Min Koo. Institutes for Pharmaceutical Discovery; Estados UnidosFil: Zhang, Mingbao. Institutes for Pharmaceutical Discovery; Estados UnidosFil: Beckett, R. Paul. Institutes for Pharmaceutical Discovery; Estados UnidosFil: Jagdmann, G. Erik. Institutes for Pharmaceutical Discovery; Estados UnidosFil: Ryder, Todd R.. Institutes for Pharmaceutical Discovery; Estados UnidosFil: Sheeler, Ryan. Institutes for Pharmaceutical Discovery; Estados UnidosFil: Andreoli, Monica. Institutes for Pharmaceutical Discovery; Estados UnidosFil: Conway, Bruce. Institutes for Pharmaceutical Discovery; Estados UnidosFil: Mahboubi, Keyvan. Institutes for Pharmaceutical Discovery; Estados UnidosFil: D’Angelo, Gerard. Institutes for Pharmaceutical Discovery; Estados UnidosFil: Mitschler, Andre. Université de Strasbourg; FranciaFil: Cousido Siah, Alexandra. Université de Strasbourg; FranciaFil: Ruiz, Frances X.. Université de Strasbourg; FranciaFil: Howard, Eduardo Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; Argentina. Université de Strasbourg; FranciaFil: Podjarny, Alberto Daniel. Université de Strasbourg; FranciaFil: Schroeter, Hagen. Mars Incorporated; Estados Unido

Ginseng on Hyperglycemia: Effects and Mechanisms

It has been reported that American ginseng attenuates hyperglycemia and may present itself as a supplement to diabetes therapy. However, the lack of standardization in the usage of ginseng root leads to inconclusive results when applied to diabetes treatment. The mechanisms of American ginseng root in the treatment of diabetes remains a mystery. This greatly limits the effective utilization of American ginseng in facilitating diabetic therapy. Initiating studies have shown that American ginseng increases insulin production and reduces cell death in pancreatic β-cells. Also, studies have revealed American ginseng's ability to decrease blood glucose in type II diabetes patients as well as in streptozotocin-induced diabetic animals (STZ-diabetic mice). These data suggest that effects of ginseng in improving hyperglycemia may alter mitochondrial function as well as apoptosis cascades to ensure cell viability in pancreatic islet cells. This review briefly summarizes current knowledge of ginseng components and clinical studies related to diabetes. Further research will be needed to explore and identify the component(s) of ginseng, which may be responsible for the beneficial effects observed in animal studies which could then be extrapolated to human islets

Pharmacokinetics of Glutathione and Its Metabolites in Normal Subjects

To determine the loading and maintenance dosage of glutathione (GSH) for patients suffering from reactive oxygen species (ROS) injury such as acute paraquat intoxication, a kinetic study of reduced GSH was performed in synchrony with that of cysteine (Cys), cystine (Cys2), and methionine (Met). Human subject's porticipitation was voluntary. The effective dose of Cys, Cys2, and Met against ROS in fibroblast cells generated by paraquat was assessed using laser scanning confocal microscopy. Both Cys and Met suppressed ROS in a dose-dependent manner at concentrations of 1-1,000 µM; the concentration required to suppress ROS by 50% was 10 µM for Cys and 50 µM for Met. Using metabolite kinetics with the assumption that Cys and Met are the metabolites of GSH, expected concentrations of Cys and Met of above 20 and 50 µM were estimated when GSH was administered at 50 mg/kg body weights every 205.4 min for Cys and 427.4 min for Met

The role of cortistatin in the human immune system

International audienc

Spatial Extent of Charge Repulsion Regulates Assembly Pathways for Lysozyme Amyloid Fibrils

Formation of large protein fibrils with a characteristic cross β-sheet architecture is the key indicator for a wide variety of systemic and neurodegenerative amyloid diseases. Recent experiments have strongly implicated oligomeric intermediates, transiently formed during fibril assembly, as critical contributors to cellular toxicity in amyloid diseases. At the same time, amyloid fibril assembly can proceed along different assembly pathways that might or might not involve such oligomeric intermediates. Elucidating the mechanisms that determine whether fibril formation proceeds along non-oligomeric or oligomeric pathways, therefore, is important not just for understanding amyloid fibril assembly at the molecular level but also for developing new targets for intervening with fibril formation. We have investigated fibril formation by hen egg white lysozyme, an enzyme for which human variants underlie non-neuropathic amyloidosis. Using a combination of static and dynamic light scattering, atomic force microscopy and circular dichroism, we find that amyloidogenic lysozyme monomers switch between three different assembly pathways: from monomeric to oligomeric fibril assembly and, eventually, disordered precipitation as the ionic strength of the solution increases. Fibril assembly only occurred under conditions of net repulsion among the amyloidogenic monomers while net attraction caused precipitation. The transition from monomeric to oligomeric fibril assembly, in turn, occurred as salt-mediated charge screening reduced repulsion among individual charged residues on the same monomer. We suggest a model of amyloid fibril formation in which repulsive charge interactions are a prerequisite for ordered fibril assembly. Furthermore, the spatial extent of non-specific charge screening selects between monomeric and oligomeric assembly pathways by affecting which subset of denatured states can form suitable intermolecular bonds and by altering the energetic and entropic requirements for the initial intermediates emerging along the monomeric vs. oligomeric assembly path

Class dynamics of development: a methodological note

This article argues that class relations are constitutive of developmental processes and central to understanding inequality within and between countries. In doing so it illustrates and explains the diversity of the actually existing forms of class relations, and the ways in which they interplay with other social relations such as gender and ethnicity. This is part of a wider project to re- vitalise class analysis in the study of development problems and experiences

Use frequency of traditional Chinese medicine in Taiwan

BACKGROUND: Use of Traditional Chinese medicine (TCM), an important category of complementary and alternative medicine (CAM), has increased substantially in Western countries during the past decade. Use of TCM is also widespread in the Chinese population. However, few informative data have been obtained to date by large-scale investigations of TCM use in the Chinese population. This study was aimed at elucidating the demographics and patterns of TCM use in Taiwan. METHODS: We employed the complete datasets of TCM outpatient reimbursement claims from 1996 to 2001, including the use of Chinese herbal remedies, acupuncture and traumatology manipulative therapy, to analyse use frequencies, the characteristics of TCM users, and the disease categories that were treated by TCM in Taiwan. RESULTS: At the end of 2001, 6,142,829 (28.4%) among the 21,653,555 valid beneficiaries of the National Health Insurance in Taiwan had used TCM during the year. However, 13,536,266 subjects (62.5%) had used TCM at least once during the whole 6-year period from 1996 to 2001, with a total of 156,224,266 visits (mean 11.5 visits per user). The mean number of TCM users per annum was 5,733,602, with a mean increment of 1,671,476 (29.2%) of new users yearly. Among TCM users, female was higher than male (female:male = 1.13:1), and the age distribution displayed a peak at around the 30s, followed by the 20s and 40s. Chinese herbal remedies (85.9%) were the most common TCM modality used by this population, followed by acupuncture (11.0%) and traumatology manipulative therapies (3.1%). Private TCM clinics provided most of the TCM care (82.6%), followed by private TCM hospitals (12.0%). The top ten major disease categories for TCM visits were diseases of the respiratory system, musculoskeletal system and connective tissue; symptoms, signs and ill-defined conditions; injury and poisoning; diseases of the digestive system, genitourinary system, skin and subcutaneous tissue, nervous system and sense organs, circulatory and endocrine system; nutritional and metabolic diseases; and immunological disorders. CONCLUSION: TCM was popular among the Chinese population in Taiwan during the period studied. More than 60% of all subjects had used TCM during the 6-year interval. TCM was widely used by the Chinese population to treat problems and diseases of major human organ systems recognised by western medicine. This study provides information about the use frequencies of TCM and the disease categories treated by TCM, which should be useful for health policy makers and for those considering the integration of TCM and Western medicine