bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential diagnosis of myelofibrosis based on WHO 2008 criteria: Acute panmyelosis with myelofibrosis, acute megakaryoblastic leukemia with myelofibrosis, primary myelofibrosis and myelodysplastic syndrome with myelofibrosis
Authors: Bae E. , Park C.‐J. , Cho Y.‐U. , Seo E.‐J. , Chi H.‐S. , Jang S. , Lee K.‐H. , Lee J.‐H. , Lee J.‐H. , Suh J.‐J. , IM H.‐J.
Published: May 2013

Introduction

The aim of this study was to characterize clinicopathological features of acute panmyelosis with myelofibrosis (APMF), acute megakaryoblastic leukemia with myelofibrosis (AMKL‐MF), primary myelofibrosis (PMF) and myelodysplastic syndrome with myelofibrosis (MDS‐MF) in order to provide the keys to the differential diagnosis of bone marrow (BM) fibrosis.

Methods

We compared age, gender, splenomegaly, serum lactate dehydrogenase level, blood cell counts, blast counts in peripheral blood (PB) and BM, megakaryocyte counts, BM cellularity, dysplasia, and the karyotypes of patients with APMF (n = 6), AMKL‐MF (n = 7), PMF (n = 44), and MDS‐MF (n = 44).

Results

APMF showed hyperplasia of all three lineages, increase in megakaryocyte count with dysplasia and frequent abnormal karyotypes. AMKL‐MF was associated with elevated BM blast counts, decreased BM megakaryocyte count with rare megakaryocytic dysplasia and chromosome 21 abnormality. PMF patients displayed splenomegaly, rare blasts in PB/BM, and JAK2 V617F mutation. MDS‐MF patients showed pancytopenia, dysplasia in all three lineages and recurrent chromosomal abnormalities involving chromosome 5,7,12, and 17.

Conclusions

Although differential diagnosis among APMF, AMKL‐MF, PMF, and MDS‐MF is very challenging due to the overlapping clinical and morphological features, meticulous investigation of the patient with respect to splenomegaly, blood cell count, PB and BM findings, and karyotype will serve as a guide to correct diagnosis.
Aortic Stiffness and Plasma Brain Natriuretic Peptide Predicts Mortality in Acute Ischemic Stroke
Authors: Biteker Murat , Özden Temel , Dayan Akin , Tekkeşin Ahmet Ilker , Misirli Cemile Handan
Published: May 2013

Background

The study aimed to evaluate the prognostic role and discriminative power of aortic stiffness and plasma brain natriuretic peptide levels in a cohort of patients hospitalized for acute ischemic stroke.

Methods and Results

Three hundred and ten consecutive patients aged 50 years and older with a first episode of acute ischemic stroke were prospectively evaluated. All patients were admitted to the hospital within 24 h of the onset of stroke symptoms. The type of acute ischemic stroke was classified according to the Trial of Org 10172 in Acute Stroke Treatment classification. Blood samples were taken for measurement of brain natriuretic peptide levels at admission. Aortic stiffness indices, aortic strain and distensibility, were calculated from the aortic diameters measured by transthoracic echocardiography. The patients were followed for one-year or until death, whichever came first. Death occurred in 51 (16·5%) patients. On multivariate logistic regression analysis, National Institutes of Health Stroke Scale score >13, diabetes, brain natriuretic peptide >235 pg/mL, aortic distensibility, and aortic strain were associated with all-cause mortality. The optimal cutoff level of brain natriuretic peptide to distinguish the deceased group from the survival group was 235 pg/mL (sensitivity 71·0% and specificity 63·0%) and to distinguish cardioembolic stroke from noncardioembolic stroke was 155 pg/mL (sensitivity 81% and specificity 63%).

Conclusions

Aortic stiffness and brain natriuretic peptide predict mortality in patients with first-ever acute ischemic stroke. Brain natriuretic peptide also differentiates cardioembolic stroke from noncardioembolic stroke.
Effect of Addition of Clopidogrel to Aspirin on Stroke Incidence: Meta-Analysis of Randomized Trials
Authors: Palacio Santiago , Hart Robert G. , Pearce Lesly A. , Anderson David C. , Sharma Mukul , Birnbaum Lee A. , Benavente Oscar R.
Published: May 2013

Background

It remains controversial whether dual antiplatelet therapy reduces stroke more than aspirin alone.

Aim

We aimed to assess the effects of adding clopidogrel to aspirin on the occurrence of stroke and major haemorrhage in patients with vascular disease.

Methods

Meta-analysis of published randomized trials comparing the combination of clopidogrel and aspirin vs. aspirin alone that reported stroke and major bleeding.

Results

Thirteen randomized trials were included with a total of 90 433 participants (mean age 63 years; 63% male) with a mean follow-up of 1·0 years and 2011 strokes. Stroke was reduced 19% by dual antiplatelet therapy (odds ratio = 0·81, 95% confidence interval 0·74–0·89) with no evidence of heterogeneity of effect across different trial populations (I2 index = 5%, P = 0·4 for heterogeneity). Dual antiplatelet therapy reduced ischemic stroke by 23% (odds ratio = 0·77; 95% confidence interval 0·70–0·85); there was a nonsignificant 12% increase in intracerebral haemorrhage (odds ratio = 1·12, 95% confidence interval 0·86–1·46). Among 1930 participants with recent (<30 days) brain ischemia from four trials, stroke was reduced by 33% (odds ratio = 0·67, 95% confidence interval 0·46–0·97) by dual antiplatelet therapy vs. aspirin alone. The risk of major bleeding was increased by 40% (odds ratio = 1·40, 95% confidence interval 1·26–1·55) by dual antiplatelet therapy.

Conclusions

This meta-analysis demonstrates a substantial relative risk reduction in stroke by clopidogrel plus aspirin vs. aspirin alone that is consistent across different trial cohorts. Major haemorrhage is increased by dual antiplatelet therapy.
Paracetamol (Acetaminophen) in Stroke 2 (PAIS 2): Protocol for a Randomized, Placebo-Controlled, Double-Blind Clinical Trial to Assess the Effect of High-Dose Paracetamol on Functional Outcome in Patients with Acute Stroke and a Body Temperature of 36·5°C or above
Authors: de Ridder Inger R. , de Jong Frank Jan , den Hertog Heleen M. , Lingsma Hester F. , van Gemert H. Maarten A. , Schreuder A. H. C. M. L. (Tobien) , Ruitenberg Annemieke , Maasland E. (Lisette) , Saxena Ritu , Oomes Peter , van Tuijl Jordie , Koudstaal Peter J. , Kappelle L. Jaap , Algra Ale , van der Worp H. Bart , Dippel Diederik W. J.
Published: May 2013

Rationale

In the first hours after stroke onset, subfebrile temperatures and fever have been associated with poor functional outcome. In the first Paracetamol (Acetaminophen) in Stroke trial, a randomized clinical trial of 1400 patients with acute stroke, patients who were treated with high-dose paracetamol showed more improvement on the modified Rankin Scale at three-months than patients treated with placebo, but this difference was not statistically significant. In the 661 patients with a baseline body temperature of 37·0°C or above, treatment with paracetamol increased the odds of functional improvement (odds ratio 1·43; 95% confidence interval: 1·02–1·97). This relation was also found in the patients with a body temperature of 36·5°C or higher (odds ratio 1·31; 95% confidence interval 1·01–1·68). These findings need confirmation.

Aim

The study aims to assess the effect of high-dose paracetamol in patients with acute stroke and a body temperature of 36·5°C or above on functional outcome.

Design

The Paracetamol (Acetaminophen) In Stroke 2 trial is a multicenter, randomized, double-blind, placebo-controlled clinical trial. We use a power of 85% to detect a significant difference in the scores on the modified Rankin Scale of the paracetamol group compared with the placebo group at a level of significance of 0·05 and assume a treatment effect of 7%. Fifteen-hundred patients with acute ischemic stroke or intracerebral hemorrhage and a body temperature of 36·5°C or above will be included within 12 h of symptom onset. Patients will be treated with paracetamol in a daily dose of six-grams or matching placebo for three consecutive days. The Paracetamol (Acetaminophen) In Stroke 2 trial has been registered as NTR2365 in The Netherlands Trial Register.

Study outcomes

The primary outcome will be improvement on the modified Rankin Scale at three-months as analyzed by ordinal logistic regression.

Discussion

If high-dose paracetamol will be proven effective, a simple, safe, and extremely cheap therapy will be available for many patients with acute stroke worldwide.
HIMALAIA (Hypertension Induction in the Management of AneurysmaL subArachnoid Haemorrhage with Secondary IschaemiA): A Randomized Single-Blind Controlled Trial of Induced Hypertension vs. no Induced Hypertension in the Treatment of Delayed Cerebral Ischemia after Subarachnoid Hemorrhage
Authors: Gathier C. S. , van den Bergh W. M. , Slooter A. J. C. ,   for the HIMALAIA-Study Group
Published: May 2013

Rationale

Delayed cerebral ischemia (DCI) is a major complication after aneurysmal subarachnoid hemorrhage (SAH). One option to treat delayed cerebral ischemia is to use induced hypertension, but its efficacy on the eventual outcome has not been proven in a randomized clinical trial. This article describes the design of the HIMALAIA trial (Hypertension Induction in the Management of AneurysmaL subArachnoid haemorrhage with secondary IschaemiA), designed to assess the effectiveness of induced hypertension on neurological outcome in patients with DCI after SAH.

Aims

To investigate whether induced hypertension improves the functional outcome in patients with delayed cerebral ischemia after SAH.

Design

The HIMALAIA trial is a multicenter, singe-blinded, randomized controlled trial in patients with DCI after a recent SAH. Eligible patients will be randomized to either induced hypertension ( n = 120) or to no induced hypertension ( n = 120). In selected centers, the efficacy of induced hypertension in augmenting cerebral blood flow will be measured by means of cerebral perfusion computerized tomography scanning. Follow-up assessments will be performed at 3 and 12 months after randomization by trial nurses who are blinded to the treatment allocation and management. We will include patients during five years.

Study outcomes

The primary outcome is the proportion of subarachnoid hemorrhage patients with delayed cerebral ischemia with poor outcome three-months after randomization, defined as a modified Rankin scale of more than 3. Secondary outcome measures are related to treatment failure, functional outcome, adverse events, and cerebral hemodynamics. The HIMALAIA trial is registered at clinicaltrials.gov under identifier NCT01613235.
Thrombolysis for Acute Ischemic Stroke in South Africa
Authors: Bryer Alan , Wasserman Sean
Published: May 2013

Background

Stroke is an important cause of death and disability in sub-Saharan Africa. Thrombolysis with recombinant tissue plasminogen activator (tPA) is the only effective therapy for acute ischaemic stroke. Essential requirements for stroke thrombolysis include availability of CT scanning and arrival at hospital within 4.5 hours of symptom onset. However, in developing countries where the prerequisites are met at certain centres, the efficacy and safety of thrombolysis have not been firmly established.

Aims

We aimed to evaluate the early outcomes and safety of stroke thrombolysis in a South African setting.

Method

We conducted a prospective observational study of all stroke patients receiving tPA for thrombolysis over the period January 2000 to February 2011. The primary outcome measure was the proportion of patients achieving significant early neurological recovery defined as an improvement of four or more points on the NIHSS score at discharge. The safety endpoint was the rate of symptomatic intracranial haemorrhage (SICH) and death.

Results

Forty-two patients received thrombolysis over the study period. Sixty-seven percent achieved significant neurological improvement. The majority of patients (53.8%) were discharged home, and by the time of discharge 17 (40.5%) were functionally independent. SICH occurred in 2 (4.8%) patients with an overall mortality rate of 7.1%.

Conclusions

Our findings indicate that the use of thrombolysis in routine clinical practice in a South African setting has similar safety and early efficacy outcomes to developed and other developing countries.
A Double-Blind Placebo-Controlled Clinical Evaluation of Multistem for the Treatment of Ischemic Stroke
Authors: Hess David C. , Sila Cathy A. , Furlan Anthony J. , Wechsler Larry R. , Switzer Jeffrey A. , Mays Robert W.
Published: May 2013

Background

There is growing interest in neurorestorative and reparative therapies after acute stroke. MultiStem® is an allogeneic cell therapy treatment comprising a population of multipotent adherent bone marrow cells that has shown safety in clinical trials of myocardial infarction and graft vs. host disease, as well as preclinical evidence of activity in stroke and other neurological damage models. MultiStem is now being evaluated in a clinical trial in patients that have suffered an ischemic stroke, in which the product is administered intravenously 24–36 h after the ischemic event.

Methods

The Phase 2 randomized, double-blind, placebo-controlled, multicenter dose-escalation trial will consist of three treatment cohorts, including a placebo group, and two treatment groups involving dose tiers of either 400 million or 1200 million cells per patient. Patients will be treated at 24–36 h after stroke. The two primary objectives are to determine the highest well-tolerated and safe single dose of MultiStem up to a maximum of 1200 million total cells in subjects with ischemic stroke and to determine the efficacy of MultiStem on functional outcome in subjects with stroke as measured by the modified Rankin Scale at 90 days. Patients will also be evaluated using the National Institutes of Health Stroke Scale and Barthel Index. The study will explore other aspects including, uniquely, the measurement of spleen size after stroke by magnetic resonance imaging or computed tomography imaging.

Conclusions and future direction

If MultiStem is safe and there is a signal of efficacy, a late stage phase IIb-III trial is planned.
Recent advances in the treatment of metastatic renal cell carcinoma
Authors: Abe Hideyuki , Kamai Takao
Published: May 2013

In the past 5 years, the treatment of patients with metastatic renal cell carcinoma has changed dramatically from being largely cytokine‐based with the emergence of targeted therapy. Following the elucidation of various molecular pathways in renal cell carcinoma, targeted agents (particularly vascular endothelial growth factor‐targeting antiangiogenic agents) now form the backbone of most therapeutic strategies for patients with metastatic renal cell carcinoma and the outcome of treatment has improved. However, many tumors eventually develop resistance to targeted therapy due to secondary mutation of the target protein or compensatory changes within the target pathway that bypass the site of inhibition. On the other hand, there are new forms of immunotherapy that hold the promise of improving the outcome for patients with metastatic renal cell carcinoma. In this article, we describe some of these new therapies, including the anti‐vascular endothelial growth factor monoclonal antibody bevacizumab, several receptor tyrosine kinase inhibitors (sorafenib, sunitinib, pazopanib, axitinib, and tivozanib), the mammalian target of rapamycin inhibitors temsirolimus and everolimus, and new immunotherapy modalities, such as anti‐cytotoxic T‐lymphocyte‐associated antigen 4 antibody and anti‐programmed cell death 1/programmed cell death‐ligand 1 antibody. We also discuss their role in the current management of patients with metastatic renal cell carcinoma.
Robot‐assisted laparoscopic renal artery aneurysm repair with selective arterial clamping
Authors: Samarasekera Dinesh , Autorino Riccardo , Khalifeh Ali , Kaouk Jihad H
Published: May 2013

Renal artery aneurysms represent a rare clinical entity, and most are managed with endovascular techniques when treatment is indicated. Laparoscopic and robot‐assisted repair of renal artery aneurysms has been described; however, few reports exist in the literature. We describe our experience with the surgical management of a 1.6‐cm right‐sided renal artery aneurysms in a 35‐year‐old man who presented with flank pain. Using the DaVinci Si surgical platform (Intuitive, Sunnyvale, CA, USA), the aneurysm was resected and the renal artery was reconstructed. Segmental branches of the renal artery were dissected and selectively clamped during resection, allowing for regional rather than global renal ischemia. Operative time was 240 min, with an estimated blood loss of 200 cc. Warm ischemia time was only regional, for a duration of 44 min. Follow‐up functional analysis showed preserved renal function in the right kidney. We describe our technique and show the technical feasibility of robot‐assisted renal artery aneurysm repair. Furthermore, use of the DaVinci Si system facilitates segmental artery dissection, and allows for selective clamping during reconstruction. This avoids global renal ischemia and optimizes functional preservation.
In Duobus Modis: Is Exemplar Causality Instrumental According to Aquinas?
Authors: Meinert John
Published: May 2013

In speaking of the divine ideas or God's creative act in general, Aquinas's favorite analogy is that of the artist. Hence, understanding the finite artisan, especially in the way his idea functions as an exemplar, is key to understanding the mentem Thomae on a whole host of issues most especially exemplar causality. This paper asks a question seeking specificity on the causality of the artist's idea and thereby exemplar causality in general. Is an exemplar cause in its primary instance (the idea) an instrument? Does an exemplar idea always cause in an instrumental mode? This paper, after delineating exemplar and instrumental causality separately, argues the affirmative. All ideas which function as exemplars also necessarily function as instruments, the objections of mediation, temporality, the relation of intellect/will, and efficient causality notwithstanding. In concluding the paper identifies three possible implications for this finding including a slight qualification of Aquinas's mature rejection of instrumental creation.
Osteocalcin is not a strong determinant of serum testosterone and sperm count in men from infertile couples
Authors: Schwetz V. , Gumpold R. , Graupp M. , Hacker N. , Schweighofer N. , Trummer O. , Pieber T. R. , Ballon M. , Lerchbaum E. , Obermayer‐Pietsch B.
Published: May 2013

Osteocalcin (OC) – released by osteoblasts and known as a marker of bone turnover – has been suggested to influence male fertility in murine models by enhancing testosterone production and sperm count. Results from clinical studies are scarce, however. The aim of this cross‐sectional study was to investigate the proposed association of OC, undercarboxylated osteocalcin (ucOC) or carboxylated osteocalcin (cOC) with testosterone and sperm count in a cohort of 159 young male adults from infertile couples. Semen analysis was performed. Testosterone, free testosterone, LH, OC and ucOC were measured in serum samples after an overnight fast. cOC and OC correlated weakly but significantly with testosterone (OC: r = 0.165, p = 0.040, cOC: r = 0.193, p = 0.017), but not after adjusting for age and body mass index (BMI) or waist–hip ratio (WHR). %ucOC (ucOC levels expressed as percentage of total OC) correlated inversely with LH (r = −0.184, p = 0.023) and remained significant after the same adjustment. No significant correlations were observed between OC, cOC, ucOC, %ucOC and sperm count, semen volume and number of vital spermatozoa. In binary logistic regression analyses, none of the parameters of OC were predictors of oligozoospermia after adjusting for age and BMI or WHR. The weak association between %ucOC and LH has marginal clinical importance because of the lack of associations of parameters of OC with testosterone and sperm count. The current data thus cannot support the notion that OC is associated with male fertility in young men from infertile couples.
A Multirelational Account of Toleration
Authors: Ferretti Maria Paola , Lægaard Sune
Published: May 2013

Toleration classically denotes a relation between two agents that is characterised by three components: objection, power, and acceptance overriding the objection. Against recent claims that classical toleration is not applicable in liberal democracies and that toleration must therefore either be understood purely attitudinally or purely politically, we argue that the components of classical toleration are crucial elements of contemporary cases of minority accommodation. The concept of toleration is applicable to, and is an important element of descriptions of such cases, provided that one views them as wholes, rather than as sets of isolated relations. We explain this by showing how certain cases of toleration are multi‐dimensional and how the descriptive concept of toleration might be understood intersectionally. We exemplify this by drawing on case studies of mosque controversies in Germany and Denmark. Finally, we propose that intersectionality is not only relevant to the descriptive concept of toleration but also captures an important aspect of normative theories of toleration. We illustrate this by discussing ideals of respect‐based toleration, which we also apply to the case studies.
Commentary: Filling out the evidence base for treatment of attention‐deficit hyperactivity disorder symptoms in children with intellectual and developmental disability: conclusions for clinicians – a response to Simonoff et al. (2013)
Authors: Eugene Arnold L.
Published: May 2013

This randomized clinical trial of methylphenidate in children with intellectual disability (ID) by Simonoff et al. (2013) advances the field in several ways useful to clinicians. The three‐figure widely representative sample more definitively confirms findings previously reported from smaller studies and studies with a differently selected sample. The medium placebo‐controlled effect size found is in line with previous more tentative suggestions for ID, such as those summarized by Aman et al. This sample, selected for ID but coincidentally including some children with autism (a third of the sample), nicely complements the RUPP Autism Network (2005) study of 72 children with autism, most of whom also had ID (mean IQ 62.6, range 16‐135). Similar effect was found in both studies, suggesting that one might expect a medium effect widely in the intellectual & developmental disability (IDD) population, with a 40‐50% response rate.
Rhetoric and argumentation: how clinical practice guidelines think
Authors: Fuller Jonathan
Published: May 2013

Introduction

Clinical practice guidelines (CPGs) are an important source of justification for clinical decisions in modern evidence‐based practice. Yet, we have given little attention to how they argue their evidence. In particular, how do CPGs argue for treatment with long‐term medications that are increasingly prescribed to older patients?

Approach and rationale

I selected six disease‐specific guidelines recommending treatment with five of the medication classes most commonly prescribed for seniors in Ontario, Canada. I considered the stated aims of these CPGs and the techniques employed towards those aims. Finally, I reconstructed and logically analysed the arguments supporting recommendations for pharmacotherapy.

Analysis

The primary function of CPGs is rhetorical, or persuasive, and their means of persuasion include both a display of their credibility and their argumentation. Arguments supporting pharmacotherapy recommendations for the target population follow a common inductive pattern: statistical generalization from randomized controlled trial (RCT) and meta‐analysis evidence. Two of the CPGs also argue their treatment recommendations for older patients in this style, while three fail to justify pharmacotherapy specifically for the older population.

Discussion

The arguments analysed lack the auxiliary assumptions that would warrant making a generalization about the clinical effectiveness of medications for the older population. Guidelines reason using simple induction, while ignoring important inferential gaps. Future guidelines should aspire to be well‐reasoned rather than simply evidence‐based; argue from a plurality of evidence; be wary of hasty inductions; appropriately limit the scope of their recommendations; and avoid making law‐like, prescriptive generalizations.
A short note on probability in clinical medicine
Authors: Upshur Ross E. G.
Published: May 2013

Probability claims are ubiquitous in clinical medicine, yet exactly how clinical events relate to interpretations of probability has been not been well explored. This brief essay examines the major interpretations of probability and how these interpretations may account for the probabilistic nature of clinical events. It is argued that there are significant problems with the unquestioned application of interpretation of probability to clinical events. The essay concludes by suggesting other avenues to understand uncertainty in clinical medicine.
Addiction: lifestyle choice or medical diagnosis?
Authors: Nutt David
Published: May 2013

The concept of addiction is under threat from the current UK government's attempt to define it as a lifestyle choice rather than an illness. This overturns the previous government's rational policy on drug treatment and is both dishonest and damaging. It is dishonest because addiction fulfils all the criteria for an illness. It is damaging because proven treatments for many addictions exist and the failure to optimize these means that more patients will die, get blood‐borne viruses, and encourage others into drug use. In this paper, I detail these issues and suggest ways to avoid irreparable damage to the current care provisions that are proving effective.
The depressed patient in a biological world: on philosophical and diagnostic strategies
Authors: Korf Jakob , Bosker Fokko
Published: May 2013

Rationale, aims and objective

We questioned: what kind of relationships between mental and neurobiological levels of complexity is or could become useful in the psychiatric practice? The concept of mind and associated mood states defended here is that they are physically emergent, subjective, qualitative, unified features of the brain. We compared our neurobiological assessment also to psychoanalytical practice (first person's perspective).

Argument

Applied to recent work on major depressive disorder (MDD), our ideas are among other supported by clinical and experimental studies on sleep deprivation, deep brain stimulation and epidemiological assessments of time‐to‐recovery.

Clinical implications

We suggest that depression is a transient state of the brain, that is mutually exclusive to the state of pleasure (in the Freudian context), rather than a disorder or disease with a characteristic time course (like many reversible somatic diseases). MDD can best be described with stochastic transition models, which is discussed in the context of a presumed brain serotonin dysfunction in depression. Our ideas invite a reconsideration of some concepts underlying current diagnostic and therapeutic approaches in the clinical practice.
TheEBM ArgumentHygieneCampaign
Authors: Cramer Peter
Published: May 2013

The campaign promotingevidence‐basedmedicine (EBM) shares similarities withJosephLister's 19th century campaign promoting surgical antisepsis. Both target medical practitioners as their primary clients, and both appeal to these clients in the manner of a public health programme, arguing that their standards are authoritative and relevant, that the clients fail to meet them, and that this failure is a problem that requires the clients to change. Both promote hygienic solutions to the problems that they identify, the problem of microbial pathogens in the case ofLister, and the process of clinical decision making in the case ofEBM. Hygienic solutions aim to operationalize standards as case‐independent procedures that can be performed as habits, and seek to identify instruments of purification against sources of contamination.EBM's solution is hygienic because it characterizes clinical decision‐making behaviour as a source of contamination and because it promotes a general procedure designed to correct it. Comparing theEBMcampaign toLister's helps to explain why some clinicians have had trouble trying to implementEBMas a decision‐making procedure in particular cases.EBMpromotes a hygienic solution, but unlikeLister, does not confront a well‐defined, empirically grounded problem. Some of the difficulties withEBMstem from a mismatch between its hygienic solution and the complexity and case‐dependency of clinical decision making.
Chemical Composition and in vitro Antimicrobial Activities of Mentha pulegium Leaves Extracts against Foodborne Pathogens
Authors: Ghazghazi Hanene , Chedia Aouadhi , Weslati Moufida , Trakhna Faten , Houssine Sebei , Abderrazak Maaroufi , Brahim Hasnaoui
Published: May 2013

The chemical composition and the biological activities of Mentha pulegium leaves extracts were evaluated. The main components of M. pulegium EO were menthone (41.7%), cis‐isopulegone (31.71%) and isomenthone (15.03%). The methanol extract of M. pulegium was rich in phenols and flavonoids. The EO showed much better antioxidant activity than the methanol extract against the DPPH and ABTS radicals scavenging. The EO showed strong antibacterial and antifungal activities against 10 tested microorganisms (Escherichia coli, Salmonella typhimurium, Staphylococcus aureus, Pseudomonas aeruginosa, Aeromonas hydrophila, Listeria monocytogenes, Bacillus cereus, Aspergillus niger, Aspergillus flavus, Candida albicans) tested whereas the methanol extract almost remained inactive. The IZ diameters and minimal inhibitrice concentration values for tested microorganisms were in the range of 15–30 mm and 0.05–0.8% (v/v), respectively. Future studies should focus on to determine the usage ability of M. pulegium EO in foods as natural preservative in effective dose.

Practical Applications

The replacement of synthetic additives by natural active compounds fosters research on the screening of medicinal plants as sources of new antioxidants. Moreover, such compounds can be used for extension of product shelf life by inhibiting the growth of foodborne spoilage bacteria. This study focused on the evaluation of biological activities of M. pulegium EO because of its application in food industries as a reasonably safe agent.

Thus, this species might be a good candidate for further investigation in developing new antioxidants, as well as preservatives in food against the well‐known causal agents of foodborne diseases and food spoilage, particularly E. coli, S. typhimurium, L. monocytogenes, P. aeruginosa and S. aureus.
Diverticulitis in the young is not more aggressive than in the elderly, but it tends to recur more often: Systematic review and meta‐analysis
Authors: Katz Lior H , Guy Daniel D , Lahat Adi , Gafter‐Gvili Anat , Bar‐Meir Simon
Published: May 2013

Background and Aim

For years, the natural course of diverticulitis in the young has been debatable in terms of its severity and recurrence rate, and no consensus has been reached regarding its treatment and timing of surgery. Thus, the study aims to evaluate by meta‐analysis the natural course of acute diverticulitis in the young.

Methods

Data were obtained from electronic databases and manual search of studies comparing the course of diverticulitis in young versus elderly patients. The age cut‐off was selected to be 40–50 years, and only studies using computed tomography as the sole modality for diagnosis were included. Primary outcomes were surgery during hospitalization and disease recurrence. Relative risks (RRs) with 95% confidence intervals (CIs) are reported.

Results

One thousand eighty publications were found, 12 of which were included. The total number of patients was 4982. Most young patients were males (RR 1.70, 95% CI 1.31–2.21), without tendency toward a more complicated disease at admission (RR 0.95, 95% CI 0.46–1.97). While there was no significant difference in the rate of surgery during hospitalization (RR 0.69, 95% CI 0.46–1.06), young patients underwent more elective surgeries (RR 2.39, 95% CI 1.82–3.15). No mortality was recorded among young patients. The disease recurrence rate was significantly higher than that of elderly patients (RR 1.70, 95% CI 1.31–2.21); however, no study specified the mean follow‐up period for each group.

Conclusions

The course of diverticulitis in the young is not more severe than that in elderly patients; however, the disease tends to recur more often. Therefore, while choosing a therapeutic regimen, factors other than age should also be considered.
Hepatic steatosis and severity‐related factors in obese children
Authors: Navarro‐Jarabo Jose Maria , Ubiña‐Aznar Esther , Tapia‐Ceballos Leopoldo , Ortiz‐Cuevas Carmen , Pérez‐Aísa M Angeles , Rivas‐Ruiz Francisco , Andrade Raul J , Perea‐Milla Emilio
Published: May 2013

Background and Aim

Obesity is an important health‐care problem in developed countries. It is considered a multisystemic disease, but it may also affect the liver, thus provoking non‐alcoholic fatty liver disease. This disease has been less extensively studied among children than among adults. We propose to analyze the prevalence of hepatic steatosis among a pediatric population within an area in southern Europe besides the variables associated with its development and severity.

Methods

Cross‐sectional study carried out on a population of children aged 6–14 years inclusive, using abdominal ultrasound as a method to determine the presence and severity of hepatic steatosis; in addition, anthropometric and blood‐tested parameters were examined to determine which of these were associated with steatosis.

Results

One hundred forty‐four children were analyzed, 84 male (58.3%). Steatosis was detected in 50 children (34.7%; 95% confidence interval [CI]: 26.0–42.0%). In six of these cases (12%), elevated aminotransferase levels were recorded. Factors found to be associated with steatosis were body mass index ≥ 99th percentile (odds ratio [OR] 3.58, 95% CI 1.16–15.6) and the level of alanine aminotransferase (ALT) (OR 1.08, 95% CI 1.03–1.13), while its severity was associated with ALT (OR 1.17, 95% CI 1.09–1.28). A level of ALT < 23.5 UI/dL predicted lack of severe steatosis with an area under receiver operating characteristic curve of 0.805 (95% CI 0.683–0.927).

Conclusions

Non‐alcoholic fatty liver disease is common in the obese pediatric population in our geographical area. High levels of ALT are associated with severe steatosis, although having ALT above the normal range is not common. Also, the lack of severity of steatosis can be predicted in a subgroup of children with obesity.
Gilbert's syndrome and the risk of death: A population‐based cohort study
Authors: Horsfall Laura J. , Nazareth Irwin , Pereira Stephen P. , Petersen Irene
Published: May 2013

Background and Aims

Gilbert's syndrome is a common familial hyperbilirubinemia that may reduce the risk of various age‐related diseases because of the antioxidant properties of bilirubin. We conducted a large cohort study using The Health Improvement Network primary care database and compared all‐cause mortality rates in those with and without Gilbert's syndrome.

Methods

Mortality rates in patients with a diagnosis of Gilbert's syndrome and raised bilirubin level (n = 4266) were compared with those of patients with similar characteristics but with normal bilirubin levels (n = 21 968). Multivariate Poisson regression was also used to estimate adjusted mortality rate ratios.

Results

During the 350 000 PYs of follow up across the Gilbert's and comparison cohorts, there were 1174 deaths. Mortality rates were 24/10 000 PYs in the Gilbert's cohort versus 50/10 000 PYs in the comparison cohort. Mortality rates were around half in patients with Gilbert's syndrome after accounting for sociodemographics and general health indicators (adjusted mortality rate ratio: 0.5 [95% confidence interval; 0.4–0.7; P < 0.001]).

Conclusions

Mortality rates observed for people with Gilbert's syndrome in the general population are almost half those of people without evidence of Gilbert's syndrome.
Delay of second‐line eradication therapy for Helicobacter pylori can increase eradication failure
Authors: Nishizawa Toshihiro , Suzuki Hidekazu , Takahashi Masahiko , Suzuki Masayuki , Hibi Toshifumi
Published: May 2013

Background and Aim

The interval between first‐line Helicobacter pylori eradication treatment and second‐line treatment may be critical to the second‐line therapeutic effect. We attempted to assess the association between the second‐line eradication rates and the treatment interval.

Methods

Data of patients, who were administered the second‐line H. pylori eradication regimen at Tokyo Medical Center between 2008 and 2012, were reviewed.

Results

Of the 148 patients enrolled, one patient dropped out. The eradication rates were 88.6% (intention‐to‐treat [ITT]) and 89.3% (per‐protocol [PP]) for early eradication group (eradication interval < 180 days, patients number 132) and 68.8% (ITT and PP) for delayed eradication group (eradication interval ≥ 180 days, patients number 16). The eradication rate in the delayed eradication group was significantly lower than in the early eradication group (P = 0.027 [ITT] and 0.021 [PP]). The eradication interval in the subjects showing eradication failure (124.0 ± 96.8 days, patients number 19) was significantly longer than those showing successful eradication (85.8 ± 56.9 days, patients number 128, P = 0.008).

Conclusion

Our results suggest that the delay of second‐line treatment should be avoided.
Influences of swallowing volume and viscosity on regulation of levator veli palatini muscle activity during swallowing
Authors: Okuno K. , Tachimura T. , Sakai T.
Published: May 2013

This study examined the aspect of the regulation of velum movement in the transition from the oral to pharyngeal phases of swallowing in relation to changes in the swallowing volume and viscosity by means of measurment of levator veli palatini muscle activity. The subjects were nine normal adults, ranging in age from 24 to 30 years. The swallowing volume was set at 1/4, 1/2 and 1 volume of the optimum volume of green tea for swallowing determined in each subject, and the viscosity was adjusted to 0, 2·0 and 4·6 Pa·s by mixing with thickener. Nine test foods were prepared in total. The electromyographic activity of the levator veli palatini muscle was monitored using bipolar hooked wire electrodes. The levator veli palatini muscle activity was defined as the integrated electromyographic wave. The mean in swallowing each test food was determined in each subject. The levator veli palatini muscle activity increased with the swallowing volume for all subjects (P < 0·05) and decreased inversely with the viscosity for six subjects (P < 0·05), but no change with the increase in the viscosity was noted for three subjects. This study clarified the aspect of the regulation of velar movement with regard to the involvement of the levator veli palatini muscle in swallowing activity with changes in the swallowing volume and viscosity.
Effect of Zinc on the Development of Brown Spot in Rice
Authors: Moreira Wiler R. , Rodrigues Fabrício Avila , Duarte Henrique Silva Silveira
Published: May 2013

Brown spot, caused by the fungus Bipolaris oryzae, is one of the most destructive diseases of rice. This study investigated the effect of zinc rates on the development of brown spot in rice. Rice plants (cv. ‘Metica‐1′) were grown in hydroponic culture amended with Zn rates (applied as ZnSO4.7H2O) of 0, 0.5, 1, 2 and 4 μm and inoculated with B. oryzae. The foliar concentration of Zn was determined. Leaf samples were assessed for disease severity, and then, area under brown spot progress curve (AUBSPC) was calculated. The relationship between Zn concentrations on leaf tissues and the rates of this micronutrient was best described by a positive linear regression model, while the relationship between the Zn rates and the AUBSPC was best described with a positive quadratic regression model. The correlation between Zn concentrations on leaf tissues and AUBSPC was positive and significant (r = 0.68, P < 0.05). The results from this study showed that high foliar concentration of Zn was associated with increasing rice susceptibility to brown spot.
Melatonin inhibits cholangiocarcinoma and reduces liver injury in Opisthorchis viverrini‐infected and N‐nitrosodimethylamine‐treated hamsters
Authors: Laothong Umawadee , Pinlaor Porntip , Boonsiri Patcharee , Pairojkul Chawalit , Priprem Aroonsri , Johns Nutjaree Pratheepawanit , Charoensuk Lakhanawan , Intuyod Kitti , Pinlaor Somchai
Published: May 2013

The human liver fluke Opisthorchis viverrini infection and N‐nitrosodimethylamine (NDMA) administration induce cholangiocarcinoma (CCA) and liver injury in hamsters. Melatonin protects against liver injury and reduces the alteration of mitochondrial structure, mitochondrial membrane potential, and mitochondrial pro‐ and anti‐apoptotic pathways in various cancer types. To investigate the chemopreventive effect of melatonin on CCA genesis and liver injury, hamsters were treated with a combination of O. viverrini infection and NDMA concurrently administered with melatonin (10 mg/kg and 50 mg/kg) for 120 days. Melatonin treatment at 50 mg/kg caused a significant reduction in liver/body weight ratios and decreased tumor volumes leading to an increase in the survival of animals. In the tumorous tissues, the high‐dose melatonin reduced DNA fragmentation and mitochondrial apoptosis by inducing anti‐apoptotic protein (Bcl‐2) in the mitochondrial fraction and down‐regulating cytochrome c, pro‐apoptotic protein (Bax), and caspase‐3 in tumor cytosol. Moreover, a high‐dose melatonin treatment significantly increased mitochondrial antioxidant enzymes and prevented mitochondrial ultrastructure changes in the tumor. Overall, melatonin has potent chemopreventive effects in inhibiting CCA genesis and also reduces liver injury in hamster CCA, which, in part, might involve in the suppression of CCA by reducing tumor mitochondria alteration.
Effects of elevated pCO2 on the metabolism of a temperate rhodolith Lithothamnion corallioides grown under different temperatures
Authors: Noisette Fanny , Duong Gwendoline , Six Christophe , Davoult Dominique , Martin Sophie
Published: May 2013

Coralline algae are considered among the most sensitive species to near future ocean acidification. We tested the effects of elevated pCO2 on the metabolism of the free‐living coralline alga Lithothamnion corallioides (“maerl”) and the interactions with changes in temperature. Specimens were collected in North Brittany (France) and grown for 3 months at pCO2 of 380 (ambient pCO2), 550, 750, and 1000 μatm (elevated pCO2) and at successive temperatures of 10°C (ambient temperature in winter), 16°C (ambient temperature in summer), and 19°C (ambient temperature in summer +3°C). At each temperature, gross primary production, respiration (oxygen flux), and calcification (alkalinity flux) rates were assessed in the light and dark. Pigments were determined by HPLC. Chl a, carotene, and zeaxanthin were the three major pigments found in L. corallioides thalli. Elevated pCO2 did not affect pigment content while temperature slightly decreased zeaxanthin and carotene content at 10°C. Gross production was not affected by temperature but was significantly affected by pCO2 with an increase between 380 and 550 μatm. Light, dark, and diel (24 h) calcification rates strongly decreased with increasing pCO2 regardless of the temperature. Although elevated pCO2 only slightly affected gross production in L. corallioides, diel net calcification was reduced by up to 80% under the 1,000 μatm treatment. Our findings suggested that near future levels of CO2 will have profound consequences for carbon and carbonate budgets in rhodolith beds and for the sustainability of these habitats.
Interspecific differentiation and gene flow between two desert poplars inferred from six vacuolar Na+/H+ exchanger loci
Authors: GUO Yu‐Peng , GUO Qiu‐Hong , WANG Juan , YAN Yan , WANG Gai‐Ni , LU Zhi‐Qiang , WU Yu‐Xia
Published: May 2013

Populus euphratica Olivier and P. pruinosa Schrenk are known for their tolerance to highly saline and arid habitats, and overlapping distribution. We examined interspecific differentiation and gene flow between these two species at six loci that encode vacuolar Na+/H+ exchanger genes. Interspecific divergence varied greatly between sampled loci and could collectively delimit the two species well. Simulations based on the isolation–migration model suggested gene flow primarily from P. euphratica into P. pruinosa. This asymmetrical gene flow may be related to the adaptive survival of the introgressed individuals. Our findings suggest that these species may have diverged in the presence of gene flow and that local adaptation may have played an important role in maintaining the distinct species lineages by restricting gene flow between them. Our results together indicate that interspecific divergence and gene flow differ greatly between members of the same gene family, possibly due to differential subfunctionalization and/or neofunctionalization during ongoing speciation of these two poplar species.
Randomized placebo‐controlled trial of mesenchymal stem cell transplantation in decompensated cirrhosis
Authors: Mohamadnejad Mehdi , Alimoghaddam Kamran , Bagheri Mohammad , Ashrafi Mandana , Abdollahzadeh Leila , Akhlaghpoor Shahram , Bashtar Maryam , Ghavamzadeh Ardeshir , Malekzadeh Reza
Published: May 2013

Background & Aims

There has been great interest in recent years to take advantage of bone marrow stem cells to treat cirrhosis. Our uncontrolled trial showed promising results for bone marrow mesenchymal stem cell (MSC) transplantation in cirrhosis. Therefore, we conducted a randomized, placebo‐controlled trial to evaluate the efficacy of autologous MSC transplantation in cirrhosis.

Methods

The enrolled patients with decompensated cirrhosis were randomly assigned to receive MSC or placebo infusions. A median of 195 million (range: 120–295 million) cultured MSCs were infused through a peripheral vein. The primary outcome was absolute changes in MELD score. Secondary outcomes were absolute changes in Child score, liver function tests and liver volumes between the MSC and placebo group 12 months after infusion.

Results

A total of 27 patients were enrolled. Of these, 15 patients received MSC and 12 patients received placebo. One patient in the MSC group and one patient in the placebo group were lost to follow‐up.

Three patients in the MSC group died of liver failure 3 months (one patient), or 5 months (two patients) after cellular infusion. The baseline MELD scores of the deceased patients were significantly higher than those who remained alive in either group (20.0 vs. 15.1; P = 0.02). The absolute changes in Child scores, MELD scores, serum albumin, INR, serum transaminases and liver volumes did not differ significantly between the MSC and placebo groups at 12 months of follow‐up.

Conclusion

Based on this randomized controlled trial, autologous bone marrow MSC transplantation through peripheral vein probably has no beneficial effect in cirrhotic patients. Further studies with higher number of patients are warranted to better clarify the impact of MSC infusion through peripheral vein or portal vein in cirrhosis.