bluuebunny/crossref_metadata_2025 huggingface dataset:
Can the 1.8 mm transnasal biopsy forceps instead of standard 2.2 mm alter rapid urease test and histological diagnosis?
Authors: Jeon Su Jin , Shin Sung Jae , Lee Kee Myung , Lim Sun Kyu , Lee Yoon Chul , Lee Myung Hee , Hwang Jae Cheol , Cheong Jae Youn , Yoo Byung Moo , Kim Jin Hong
Published: April 2012

Background and Aim:  Biopsy specimens are taken during transnasal esophagogastroduodenoscopy with 1.8 mm forceps. The aims of this study were to compare the concordance of the Campylobacter‐like organism (CLO) test and histological diagnoses between biopsies taken with 1.8 mm and 2.2 mm forceps and to determine whether the concordance of the CLO test could be improved by increasing the number of specimens using 1.8 mm forceps.

Methods:  A total of 200 patients were enrolled. We first performed the CLO test twice using each sample taken with both forceps in 100 patients. The CLO test was conducted three times again after confirming the difference in the CLO test between two forceps: (i) one sample with 1.8 mm forceps; (ii) two with 1.8 mm; and (iii) one with 2.2 mm in the other 100 patients. Additionally, each specimen was taken from the same gastric lesions in 200 patients for the histological diagnosis using both forceps types.

Results:  The concordance rate of the CLO test between each sample with 1.8 mm and 2.2 mm forceps was 83% (κ‐value, 0.64), and that between two samples with 1.8 mm and one with 2.2 mm was 92% (κ‐value, 0.83). The concordance rate of the histological diagnosis with 1.8 and 2.2 mm was 97% (κ‐value, 0.84).

Conclusions:  At least two samples using 1.8 mm forceps might be needed to obtain similar results on the CLO test using 2.2 mm. But, the size difference between two forceps did not influence the histological diagnosis.
Wegener's granulomatosis: treatment and survival characteristics in a high‐prevalence southern hemisphere region
Authors: Khan A. R. , Chapman P. T. , Stamp L. K. , Wells J. E. , O'Donnell J. L.
Published: April 2012

Our aim was to describe the treatment and survival characteristics of Wegener's granulomatosis (WG) in Canterbury, New Zealand. The medical records of 48 patients diagnosed between 1 July 1997 and 31 December 2008 and fulfilling validated classification criteria for WG were reviewed to characterise survivorship in the province of Canterbury, New Zealand. The age at diagnosis was 61 years (range 20 to 83 years) with an equal number of males and females. Using Kaplan–Meier product‐limit analysis, the probability of survival at 1 and 10 years was 91% and 62% respectively. Of the 12 deaths in the cohort, four occurred within 12 months of diagnosis: two from pulmonary haemorrhage and two from renal failure. Beyond 12 months, two patients died of renal failure, two of myocardial infarction and one from cardiac arrhythmia, one from cerebrovascular disease and two from colorectal carcinoma. The median time to relapse was 6.75 years, and the probability of relapse within 10 years was 67%. Survivorship, treatment response rate and the rate of relapse from WG in a cohort of patients from this high‐prevalence southern hemisphere region were similar to that reported for northern hemisphere cohorts with a similar prevalence.
How to select the doctors of the future
Authors: Oates K. , Goulston K.
Published: April 2012

Although previous academic performance is acknowledged as the best predictor of achievement in medical school, no one has succeeded in finding a selection method which will choose students who will become doctors with the qualities the community expect. Australian medical schools use various selection methods. It could well be argued that the most important phase in the selection process is informed decision‐making by potential applicants. More effort should be made by medical schools to achieve this.
Intravenous immunoglobulins as treatment of severe cutaneous polyarteritis nodosa
Authors: Marie I. , Miranda S. , Girszyn N. , Soubrane J.‐C. , Vandhuick T. , Levesque H.
Published: April 2012

We describe three patients with severe refractory cutaneous polyarteritis nodosa, resulting in painful ulcers involving the lower limbs and causing toe necrosis. Due to the severity of the cutaneous manifestations, the three patients received intravenous immunoglobulins at a dose of 1 g/kg/day for 2 days monthly. After the second intravenous immunoglobulin infusion, skin signs dramatically improved and completely healed after the third intravenous immunoglobulin infusion. Our findings indicate that intravenous immunoglobulins can be included in a therapeutic strategy to treat refractory cutaneous polyarteritis nodosa.
Utility, or not, of estimates of glomerular filtration rate in modifying drug dosage, with particular reference to enoxaparin
Authors: Adam W. R.
Published: April 2012

A reduced clearance of some drugs in renal failure is a problem, particularly with drugs that are excreted by the kidney substantially unmetabolised and also have significant toxicity and a low therapeutic ratio. The problem is compounded by the significant inaccuracy of estimated glomerular filtration rate (eGFR). The aim was to develop general recommendations to reduce the risk of drug toxicity in renal failure, with particular reference to enoxaparin.

The substantial inaccuracies in eGFR (eGFR in 32% of patients is different from measured GFR by 20–30%) are compounded when using a dichotomous decision tree (renal failure or not). As the eGFR approaches the GFR decision boundary, for classification as renal failure or not, misclassification approaches 50%.

Recommendations, when patients are at risk, include the following: acknowledge inaccuracies of eGFR, particularly in anthropometrically diverse populations; measure drug levels wherever possible; realise that drug levels after early doses relate more to volume of distribution, rather than renal function, allowing time for modification of the drug dose; where accurate urine collection is feasible, use creatinine clearance as an estimate of GFR; and use eGFR as a (more) continuous, rather than dichotomous, variable to adjust dosage, exampled by enoxaparin.
Cancer and quackery
Authors: Irving K. B.
Published: April 2012

The Internal Medicine Journal published an article by two senior oncologists who were contesting the supposed miracle cure of a cancer survivor. This paper draws on the history of medicine to explore the conflict between biomedicine and alternative therapies. I suggest that the Internal Medicine Journal article, written about an episode that occurred more than 30 years ago, can best be explained by some oncologists' discomfort with losing their authority to dictate patient choices. I propose a compromise that rejects paternalism but accepts the possibility of worse patient outcomes.
Mental health education programmes for generalist health professionals: An integrative review
Authors: Brunero Scott , Jeon Yun‐Hee , Foster Kim
Published: April 2012

Mainstreaming of mental health services has led to an increase in the presentation and care of mental health patients in generalist health settings. The lack of adequate mental health educational preparation of general health professionals (GHP) has been identified as a major barrier to meeting the health‐care needs of mental health patients. This study aimed to review and synthesize research evidence on mental health education programmes (MHEP) that have been designed to develop the knowledge, skills, and attitudes of GHP. An integrative literature review was conducted following a search of key electronic databases and hand searching of references of relevant papers, and 25 papers met the study inclusion criteria. Knowledge, skill, and attitudinal improvements in GHP post MHEP were shown in most studies. MHEP that included supervised clinical experience, role play, and case scenarios were reported as being more effective. Issues such as patient participation in education, interprofessional education models, and the willingness, interest and, motivation for GHP to be involved in MHEP warrant further research.
High cellular organization of pyoverdine biosynthesis in Pseudomonas aeruginosa: clustering of PvdA at the old cell pole
Authors: Guillon Laurent , El Mecherki Maher , Altenburger Stephan , Graumann Peter L. , Schalk Isabelle J.
Published: April 2012

Pyoverdine I (PVDI) is the major siderophore produced by Pseudomonas aeruginosa PAO1 to import iron. Its biosynthesis requires the coordinated action of cytoplasmic, periplasmic and membrane proteins. The individual enzymatic activities of these proteins are well known. However, their subcellular distribution in particular areas of the cytoplasm, periplasm, or within the membrane has never been investigated. We used chromosomal replacement to generate P. aeruginosa strains producing fluorescent fusions with PvdA, one of the initial enzymes in the biosynthetic pathway of PVDI in the cytoplasm, and PvdQ, involved in the maturation of PVDI in the periplasm. Cellular fractionation indicated that a substantial amount of PvdA‐YFP was located in the membrane fraction. Epifluorescence microscopy imaging showed that PvdA‐YFP was mainly clustered at the old cell pole of bacteria, indicating a polar segregation of the protein. Epifluorescence and TIRF imaging on cells expressing labelled PvdQ showed that this enzyme was uniformly distributed in the periplasm, in contrast with PvdA‐YFP. The description of the intracellular distribution of these enzymes contributes to the understanding of the PVDI biosynthetic pathway.
Practice‐setting and surgeon characteristics heavily influence the decision to perform partial nephrectomy among American Urologic Association surgeons
Authors: Weight Christopher J. , Crispen Paul L. , Breau Rodney H. , Kim Simon P. , Lohse Christine M. , Boorjian Stephen A. , Thompson R. Houston , Leibovich Bradley C.
Published: April 2012

What's known on the subject? and What does the study add?

There is great variability in the utilization of partial nephrectomy, but the causes of these variations are not well understood.

The present study underscores the already observed phenomenon of surgical volume influencing surgical planning and outcomes, but it gets at why this might be so. We observe that high‐volume renal surgeons have different thresholds of ‘technical feasibility’.

Objective

To investigate why there continues to be wide variability in the application of partial nephrectomy (PN) for treating small renal masses despite guidelines in the US and Europe stating that a PN is a standard of care for a patient with a T1 renal mass.

Patients and Methods

In June 2009, 764 surgeon‐members of the American Urologic Association (AUA) participated in a survey evaluating the management of renal masses.

Renal mass complexity was graded by nephrometry score (NS).

Multivariable logistic regression models with generalized estimating equations were constructed to evaluate how tumour, surgeon and practice‐setting characteristics influence the use of PN.

Results

The survey response rate was 19%. Each urological surgeon responded to eight scenarios, providing 6112 evaluable cases.

Tumour NS ranged from 4 to 10, and each unit increase in NS was associated with 59% increased likelihood of a surgeon offering RN on multivariable analysis (odds ratio [OR] = 1.59; 95% CI: 1.52–1.64).

When holding patient and tumour characteristics constant, the following surgeon and practice‐setting characteristics significantly increased the odds of offering a PN: increasing renal case volume (OR = 1.57; 95% CI: 1.27–1.95), academic practice (OR = 1.80; 95% CI: 1.42–2.29), increasing PN % volume (OR = 3.7; 95% CI: 2.46–5.55) and younger surgeon age (≤40 vs >50 years) (OR = 1.64; 95% CI: 1.35–1.96).

Conclusion

The characteristics of a surgeon and the setting in which he or she practices influence the utilization of PN, the adherence to professional guidelines, and the threshold of tumour complexity at which a surgeon stops offering PN.
Prognostic role of tumour multifocality in renal cell carcinoma
Authors: Siracusano Salvatore , Novara Giacomo , Antonelli Alessandro , Artibani Walter , Bertini Roberto , Carini Marco , Carmignani Giorgio , Ciciliato Stefano , Cunico Sergio Cosciani , Lampropoulou Nikolitsa , Longo Nicola , Martorana Giuseppe , Minervini Andrea , Mirone Vincenzo , Simeone Claudio , Simonato Alchiede , Valotto Claudio , Zattoni Filiberto , Ficarra Vincenzo ,   members of the SATURN Project – LUNA Foundation
Published: April 2012

Study Type – Therapy (multi‐centre cohort)

Level of Evidence 3b

What's known on the subject? and What does the study add?

In RCC about 5% of the patients presented multifocal disease. Prevalence of tumour multifocality was associated with a higher percentage of symptomatic RCC, higher pathological TNM stages, higher tumour grade and higher prevalence of tumour necrosis.

Although in univariable analysis multifocal tumours had lower probability of CSS, tumour multifocality did not retain an independent predictive role in multivariable analysis. Patient age at surgery, gender, mode of presentation, pathological N stage and presence of metastases were independent predictors of CSS in multivariable analyses.

OBJECTIVE

To evaluate the prevalence and the prognostic role of multifocality in a large multi‐institutional series of patients who underwent radical or partial nephrectomy for renal cell carcinoma (RCC).

METHODS

We retrospectively collected the data of 5378 patients who were surgically treated for RCC in 16 academic centres involved in the Surveillance and Treatment Update Renal Neoplasms (SATURN) project.

Univariable and multivariable Cox regression models addressed time to cancer‐specific survival (CSS) after surgery.

RESULTS

Tumour multifocality was identified in 249 patients (5%). The median follow‐up of the whole cohort was 42 months. At last follow‐up, 786 (14.6%) were dead of cancer and 336 (6.2%) had experienced non‐cancer‐related death.

The 5‐ and 10‐year CSS estimates were 84.1% and 77.3%, respectively, in patients with monofocal RCC, compared with 71.1% and 63.6%, respectively, in patients with multifocal disease (P < 0.001).

In univariable Cox regression analysis, tumour multifocality was significantly associated with CSS (hazard ratio [HR]= 1.83; P < 0.001).

On multivariate Cox regression analysis adjusted for the effects of other covariates, tumour multifocality did not retain an independent predictive value (HR = 1.24; P= 0.291).

CONCLUSIONS

In the present multi‐institutional collaboration, about 5% of the patients presented multifocal RCC.

The presence of multifocal cancer was associated with some unfavourable clinical and pathological features.

Although in univariable analysis multifocal tumours had lower CSS probabilities, tumour multifocality did not retain an independent predictive role in multivariable analysis, once adjusted for the effect of the other clinical and pathological covariates.
Role of magnetic resonance imaging in bladder cancer: current status and emerging techniques
Authors: Green David A. , Durand Matthieu , Gumpeni Naveen , Rink Michael , Cha Eugene K. , Karakiewicz Pierre I. , Scherr Douglas S. , Shariat Shahrokh F.
Published: April 2012

What's known on the subject? and What does the study add?

According to current treatment guidelines, magnetic resonance imaging (MRI) or computed tomography (CT) can be used to assist in staging bladder cancer patients being considered for radical surgery.

In this article, we review the evidence supporting the use of MRI for bladder cancer staging. The ability of MRI to differentiate non‐muscle invasive from muscle‐invasive bladder cancer, to differentiate organ‐confined from non‐organ‐confined bladder cancer, and to identify lymph node metastases is described in detail. Additionally, the role of MRI as a biomarker of chemotherapeutic response in bladder cancer is reviewed and summarized.

OBJECTIVES

• To evaluate the current status of magnetic resonance imaging (MR) as a staging tool for bladder cancer.

• To investigate the role of MR in assessing chemotherapeutic response in bladder cancer patients.

PATIENTS AND METHODS

• A Pubmed/MEDLINE search was conducted to identify original articles, review articles, and editorials regarding the use of MR in bladder cancer.

RESULTS

• Contrast‐enhanced MR and diffusion weighted MR (DW‐MRI) can likely distinguish between non‐muscle invasive bladder cancer and muscle invasive cancer with >80% accuracy.

• Some advantages of DW‐MRI are the differentiation of benign versus malignant tissue involvement without the need for intravenous contrast, and the possibility of obtaining information on histologic grade and T stage.

• Traditional MR sequence have low sensitivity for identifying small lymph node metastases but MR lymphography (MRL) using ultra‐small paramagnetic iron oxide (USPIO) may enhance their detectin.

• There may be a role for DW‐MRI in the evaluation of chemotherapeutic response in bladder cancer patients.

CONCLUSION

• To date, sample sizes and study designs are insufficient to clearly establish the role of MR in bladder cancer management, and to this end, well designed prospective trials are needed.
The association between body mass index and musculoskeletal foot disorders: a systematic review
Authors: Butterworth P. A. , Landorf K. B. , Smith S. E. , Menz H. B.
Published: April 2012

The primary aim of this systematic review was to investigate the relationship between body mass index (BMI) and foot disorders. The secondary aim was to investigate whether weight loss is effective for reducing foot pain. Five electronic databases (Ovid MEDLINE, Ovid EMBASE, Ovid AMED, CINAHL and The Cochrane Library) and reference lists from relevant papers were searched in April 2011. Twenty‐five papers that reported on the association between BMI and musculoskeletal foot disorders met our inclusion criteria and were reviewed. The evidence indicates: (i) a strong association between increased BMI and non‐specific foot pain; and (ii) a strong association between increased BMI and chronic plantar heel pain in a non‐athletic population. The evidence is inconclusive regarding the relationship between BMI and the following specific disorders of the foot; hallux valgus, tendonitis, osteoarthritis and flat foot. With respect to our second aim, there were only two prospective cohort studies that reported a reduction in foot symptoms following weight loss surgery. In summary, increased BMI is strongly associated with non‐specific foot pain in the general population and chronic plantar heel pain in a non‐athletic population. However, there is currently limited evidence to support weight loss to reduce foot pain.
HUMAN CAPITAL DISTRIBUTION, GROWTH AND TRADE
Authors: Lee Cheng‐Te , Huang Deng‐Shing
Published: April 2012

Distribution differences in human capital matter for a country's growth and trade. While the existing literature considers only the diversity difference in talent distribution, we argue that the kurtosis difference is also an important factor. In a two‐sector equilibrium growth model, where the production function is supermodular for the consumption‐good sector and submodular for the R&D sector, we prove that the diversity effect and kurtosis effect are opposite to each other. A country endowed with more diverse but leptokurtic talent distribution may have lower growth rate and import submodular goods, opposite to the conventional result from considering only the diversity difference.
Should the Good and the Selfish be Taxed Differently?*
Authors: Long Ngo Van , Stähler Frank
Published: April 2012

In this paper, we consider an environment where individual actions have externalities and two types of agents exist: agents with social preferences (the good) and selfish agents. Selfish agents have pay‐off functions that do not take into account social welfare. The pay‐off of an agent is a linear combination of social welfare and the pay‐off of a selfish agent. We demonstrate that the corrective tax rates that maximize social welfare do not depend on the degree of social preferences. Hence, the good and the selfish should not be taxed differently.
Voters as Fiscal Liberals: Incentives and Accountability in Federal Systems
Authors: Jones Mark P. , Meloni Osvaldo , Tommasi Mariano
Published: April 2012

Most empirical evidence indicates voters penalize deficits and spending growth. Contrary to this dominant finding, a few recent studies conclude that voters reward public spending. We reconcile these conflicting findings, positing that the structure of fiscal federalism in countries like Argentina causes voters to reward fiscal expansion because they perceive that this extra spending at the margin is not financed by them, but rather by the nation at large. We provide evidence and microfoundations for the electoral connection implicit in this argument: voters reward public spending when they can pass the cost on to someone else (e.g., as in Argentina), and punish it otherwise (e.g., as in the United States).
Determinants of Expected Stock Returns: Large Sample Evidence from the German Market
Authors: Artmann Sabine , Finter Philipp , Kempf Alexander
Published: April 2012

Abstract:  This paper conducts a comprehensive asset pricing study based on a unique dataset for the German stock market. For the period 1963 to 2006 we show that value characteristics and momentum explain the cross‐section of stock returns. Corresponding factor portfolios have significant premiums across various double‐sorted characteristic‐based test assets. In a horse race of competing asset pricing models, the Fama‐French 3‐factor model does a poor job in explaining average stock returns. The Carhart 4‐factor model performs much better, but a 4‐factor model containing an earnings‐to‐price factor instead of a size factor does even slightly better.
Scaling up by law? Canadian labour law, the nation‐state and the case of the British Columbia Health Employees Union
Authors: Rutherford Tod D
Published: April 2012

This paper examines the Canadian Supreme Court’s 2007 ruling in favour of the Health Employees Union (HEU) versus the British Columbia government. Based on international labour law, this ruling recognised collective bargaining as part of the Canadian Charter of Rights and Freedoms. While recent research in human and labour geography on labour law and the state have emphasised its contingent, topological and site‐based nature I argue: (i) that this case reflects how Canadian unions became deeply embedded in post‐war hegemonic splicings of law and space and the state’s role in the reproduction of the wage‐labour relation and (ii) while the HEU’s struggles and the use of international law contest such splicings, these are still sharply inflected by existing nation‐state legal systems that remain both relatively resilient and ambivalent about labour rights. The HEU case thus reveals that scaling up by law may not protect worker interests if labour is otherwise weak.
Effect of RhoA on transforming growth factor β1‐induced rat hepatic stellate cell migration
Authors: Li Lei , Wang Ji‐Yao , Yang Chang‐Qing , Jiang Wei
Published: April 2012

Background

Although the migration of hepatic stellate cells (HSCs) is essential to the hepatic fibrotic response, the intracellular and extracellular signals that regulate their migration are poorly understood.

Aims

To investigate the role of Rho guanosine triphosphatase (Rho GTPase) signalling, specifically via RhoA, in transforming growth factor β1 (TGFβ1)‐induced HSC migration.

Methods

Both primary rat HSCs and the HSC‐T6 rat hepatic stellate cell line were used in this study. Cell migration was evaluated using the Transwell Boyden Chamber assay, whereas cytoskeletal changes were observed using laser confocal microscopy. Western blotting was used to detect the expression of Rho GTPases (RhoA, Rac1 and Cdc42) in HSCs, and their activation was determined using glutathione S‐transferase (GST) pull‐down assays. Finally, the specific effects of RhoA on TGFβ1‐induced cell migration were analysed in HSC‐T6 cells stably transfected with constitutively active (CA, Q63L) or dominant‐negative (DN, T19N) RhoA mutants.

Results

Transforming growth factor β1 induced cytoskeletal remodelling and migration of rat HSCs following RhoA activation. The level of RhoA activation determined the motility of the HSCs.

Conclusions

These findings broaden our understanding of the intracellular and extracellular signals that regulate HSC migration. Furthermore, RhoA may be a candidate therapeutic target for hepatic fibrosis.
Two‐Dimensional Speckle‐Tracking Echocardiography Reveals Systolic Abnormalities in Granulomatosis with Polyangiitis (Wegener’s)
Authors: Miszalski‐Jamka Tomasz , Szczeklik Wojciech , Nycz Krzysztof , Sokołowska Barbara , Górka Jacek , Bury Krzysztof , Musiał Jacek
Published: April 2012

Background: Two‐dimensional speckle‐tracking echocardiography (STE) is a novel technique providing accurate assessment of myocardial function. However, its value in granulomatosis with polyangiitis (Wegener’s) (WG) has not been studied. Objective: To assess the presence and frequency of systolic left ventricular (LV) dysfunction using STE and to determine incremental value of STE over standard echocardiography to detect myocardial abnormalities in WG. Methods: Twenty‐two WG patients (11 males, 11 females, mean age 46.8 ± 12.3 years) and 22 sex‐ and age‐matched healthy subjects underwent standard and STE. Global longitudinal, circumferential, and rotational deformation parameters were calculated. Results: All patients had LV ejection fraction (EF) >50%. LVEF was 65.0 ± 7.5% and LV end‐diastolic volume index 44.8 ± 11.8 mL/m2. Regional LV wall motion abnormalities were found in 7 (32%), while abnormal global STE determined systolic dysfunction in 16 (73%) subjects (P = 0.008). Global longitudinal, circumferential and radial peak‐systolic deformational parameters (strain or strain rate) were decreased in 11 (50%), 9 (41%), and 3 (14%) patients (P = 0.02), respectively. Comparing patients with abnormal and normal STE derived global systolic function, the former had higher cumulative disease extent index (10.6 ± 3.0 vs 7.5 ± 1.8; P = 0.03) and vasculitis damage index (7.9 ± 1.9 vs 6.0 ± 1.7; P = 0.04). Conclusions: Despite normal LVEF the global systolic LV abnormalities detected by STE are common in WG. They correspond to the extent and severity of WG and are more frequent than regional wall motion abnormalities in standard echocardiography.
Velocity Vector Imaging Fails to Quantify Regional Myocardial Dysfunction in a Mouse Model of Isoprenaline‐Induced Cardiotoxicity
Authors: Täng Margareta Scharin , Redfors Bjorn , Shao Yangzhen , Omerovic Elmir
Published: April 2012

Background: Regional myocardial deformation patterns are important in a variety of cardiac diseases, including stress‐induced cardiomyopathy. Velocity‐vector‐based imaging is a speckle‐tracking echocardiography (STE)‐based algorithm that has been shown to allow in‐depth cardiac phenotyping in humans. Regional posterior wall myocardial dysfunction occurs during severe isoprenaline stress in mice. We have previously shown that regional posterior wall end‐systolic transmural strain decreases after severe isoprenaline toxicity in mice. We hypothesize that STE can detect and further quantify these perturbations. Methods and results: Twenty‐three mice underwent echocardiographic examination using the VEVO2100 system. Regional transmural radial strain and strain rate were calculated in both parasternal short‐axis and parasternal long‐axis cine loops using the VisualSonics VEVO 2100 velocity vector imaging (VVI) STE algorithm. Eight C57BL/6 mice underwent baseline echocardiographic examination using the VisualSonics VEVO 770 system, which can acquire >1,000 frames/s cine loops. In a parasternal short‐axis cine loop, the heart was divided into six segments, and regional fractional wall thickening (FWT) was assessed manually. The same protocols were also performed 90 minutes post 400 mg/kg intraperitoneally isoprenaline. Regional myocardial FWT is uniform at baseline but increases significantly in anterolateral segments, whereas it decreases significantly in posterior segments (P < 0.05). A similar pattern is seen using the VVI algorithm although the variance is larger, and differences are smaller and fail to reach significance. Conclusions: VVI is less sensitive in detecting regional perturbations in myocardial function than manual tracing, possibly due to the low frame rate in the cine loops used.
Roles of BCL6 in normal and transformed germinal center B cells
Authors: Basso Katia , Dalla‐Favera Riccardo
Published: April 2012

Summary:  BCL6 is a transcriptional repressor required in mature B cells during the germinal center (GC) reaction. Multiple mechanisms act coordinately to timely modulate BCL6 expression at transcriptional and post‐transcriptional levels. BCL6 prevents premature activation and differentiation of GC B cells and provides an environment tolerant of the DNA breaks associated with immunoglobulin gene remodeling mechanisms involved in the production of high‐affinity antibodies of different isotypes. The critical functions exerted by BCL6 during normal B‐cell development can be hijacked by the malignant transformation process. Indeed, BCL6 is targeted by genetic aberrations and acts as an oncogene in GC‐derived lymphomas. The aberrations affecting BCL6 interfere with the multiple levels of regulation that grant a fine tuning of BCL6 expression and activity in physiologic conditions. This review summarizes the current knowledge on BCL6 function and its role in lymphomagenesis.
Contribution of Toll‐like receptor signaling to germinal center antibody responses
Authors: DeFranco Anthony L. , Rookhuizen Derek C. , Hou Baidong
Published: April 2012

Summary:  Toll‐like receptors (TLRs) have emerged as one of the most important families of innate immune receptors for initiating inflammation and also for promoting adaptive immune responses. Recent studies have examined the ability of TLRs to promote antibody responses, including T‐cell‐dependent antibody responses. Initial study suggested that TLR stimulation promotes primarily an extrafollicular antibody response, which rapidly produces moderate affinity antibodies made by short‐lived plasma cells. Recent studies, however, have shown that TLRs can also enhance the germinal center response, which produces high affinity class‐switched antibody made by long‐lived plasma cells. TLR stimulation can increase the magnitude of the latter response and also enhance selection for high affinity IgG. This review summarizes recent advances in understanding the roles of TLRs in B cells and also in other cell types for enhancement of antibody responses, with an emphasis on T‐cell‐dependent and germinal center antibody responses.
Differentiation of germinal center B cells and follicular helper T cells as viewed by tracking Bcl6 expression dynamics
Authors: Okada Takaharu , Moriyama Saya , Kitano Masahiro
Published: April 2012

Summary:  Development of germinal center (GC) B cells and follicular helper T (Tfh) cells requires the transcription factor B‐cell lymphoma 6 (Bcl6). Expression of Bcl6 in B cells and helper T cells is regulated by complex signals including those generated through their antigen‐specific interactions, which take place in various microenvironments depending on their activation/differentiation states. In the last several years, it has become possible to detect Bcl6 protein in individual B cells and T cells by intracellular staining with the newly developed antibodies or by using the reporter mice. Experiments using these reagents have started to clarify microanatomical location of early Bcl6 upregulation in B cells and T cells, and contributed to reveal the dispensability and indispensability of B cells in the early and late phase of Tfh differentiation. They also started to reveal the diversity, plasticity, and/or instability of Tfh cells. We summarize the recent findings made by tracking Bcl6 expression together with the updated knowledge about dynamics of antigen‐engaged B cells and helper T cells and discuss them in relation to possible signaling requirements for the development of GC B cells and Tfh cells.
T‐follicular helper cell differentiation and the co‐option of this pathway by non‐helper cells
Authors: Linterman Michelle A. , Liston Adrian , Vinuesa Carola G.
Published: April 2012

Summary:  Human and mouse studies performed over the last decade have established that follicular helper T (Tfh) cells are a CD4+ helper subset specialized in the provision of help to B cells. Tfh differentiation is driven by expression of the transcriptional repressor B‐cell lymphoma‐6 (Bcl‐6), which turns on a program that guides T cells close to B‐cell areas where Tfh cells first provide help to B cells. Sustained Bcl‐6 expression promotes the entry of Tfh cells into follicles and modulates their cytokine expression profile so they can support and select germinal center B cells that have acquired affinity‐enhancing mutations in their immunoglobulin genes. Forkhead box 3 protein (Foxp3)+ regulatory T cells and invariant natural killer T (NKT) cells can also co‐opt the Bcl‐6‐dependent follicular differentiation pathway to migrate into B‐cell follicles and regulate antibody responses. The resulting NKT follicular helper cells drive a distinctive type of T‐dependent B‐cell response to lipid‐containing antigens, whereas FoxP3+ follicular regulatory (Tfr) cells exert a suppressive function on germinal centers. Elucidating how Tfr cells are functionally and numerically regulated and the factors that control the balance between Tfh and Tfr cells is likely to be critical for improved understanding of the pathogenesis and progression of autoimmunity and lymphomas of germinal center origin, and generation of effective vaccines.
Germinal center selection and the development of memory B and plasma cells
Authors: Shlomchik Mark J. , Weisel Florian
Published: April 2012

Summary:  A hallmark of adaptive immune responses is the generation of long‐lived protection after primary exposure to a pathogen. In humoral responses, this protection stems from a combination of sustained antibody titers and long‐lived memory B cells (MBCs), with the former deriving from long‐lived plasma cells (PCs). Both types of cell are thought to primarily derive from the germinal center (GC), a unique structure that forms during the immune response to many types of antigenic stimuli. GCs are seeded by antigen‐specific B and T cells that were previously activated in the early stages of the response. The GC does not directly or immediately generate effector function; rather, it is a site of intense B‐cell proliferation and cell death. GC B cells undergo both somatic hypermutation and isotype switch, and a Darwinian process very efficiently selects B cells with higher fitness for survival and expansion. GC B cells adopt a unique activation and transcriptional state, and the cells become poised to differentiate to either MBCs or PCs. Despite this general understanding of the events in the GC, the mechanisms that control both affinity selection as well as differentiation have not been well worked out. In this review, we address what is known about what determines whether GC B cells become MBCs or PCs. This is discussed in the broader context of the origins of both cell types, whether from the GC or potentially other sources. We present a model encompassing recent data from several laboratories including our own that suggests that the GC undergoes a temporal switch that alters the nature of its output from MBCs to PCs as the response progresses. We will discuss B‐cell receptor signaling in the GC as it relates to potential mechanisms for affinity‐based selection during the reaction.
To Change or Not to Change Horses: The World War II Elections
Authors: NORPOTH HELMUT
Published: April 2012

Folk wisdom counsels voters to stick with leaders in time of a war, though recent experience suggests otherwise. Taking advantage of largely unexplored polls from the 1940s (Gallup and National Opinion Research Center), this research probes vote choices in the World War II elections. Of particular interest is a counterfactual question that asked respondents how they would have voted if there was no war. In addition, the aggregate vote in presidential contests over time is used to estimate how the White House party fares in wartime elections. President Roosevelt received a special premium in electoral support from the wartime condition in both 1940 and 1944. This premium was earned through popular support for war‐related issues. Hence, in wartime elections where such support is lacking voters may be inclined to change horses.
Signing Statements as Bargaining Outcomes: Evidence from the Administration of George W. Bush
Authors: WHITFORD ANDREW B.
Published: April 2012

Recent studies have documented how presidents issue signing statements. A president might try to bend policy closer to his own position through shaping how bureaucrats use their discretion to implement a law. Later in time, it may serve as a defense if it shapes how judges decide whether a particular interpretation is consistent with the Constitution. A president may construct more detailed and complex statements when his ideal point is distant from Congress. I test this hypothesis and others using data from the George W. Bush administration between 2001 and 2006. Both the number of objections applied to a given bill and their complexity increase when the president is distant from Congress.
Physical activity promotion in primary care targeting the older adult
Authors: Neidrick Thad J. , Fick Donna M. , Loeb Susan J.
Published: April 2012

Purpose: This integrative review identifies and examines research literature focused on physical activity promotion provided in primary care settings to older adult patients in order to evaluate the effectiveness of provider‐delivered interventions on elders short‐ and long‐term activity levels.

Data Resources: A comprehensive review of original research published in English from all countries through May 2010 was performed. Relevant literature was identified through MEDLINE, CINAHL, and ProQuest on‐line databases. Data from 11 unique studies were systematically extracted and summarized in table format.

Conclusions: Activity interventions delivered in primary care can produce at least short term increases in activity; however, there is limited evidence to evaluate whether long‐term changes can be achieved and thus making the case for future longitudinal studies.

Implications for Practice: Tailored activity prescriptions should be provided after holistic patient assessment. Activity counseling requires recognition as a billable service and further study is needed to identify the most efficient intervention. Inclusion of health‐economic evaluations in future research could reveal if efforts to improve physical activity levels are an efficient use of resources.
Zur Kenntnis der durch die zentripetalen Muskelnerven hervorgerufenen Reflexe an den hinteren Extremitäten des Kaninchens1
Authors: Airila Y. , Loimaranta E.
Published: April 2012

. Die kutanen Nerven wie die zentripetalen Muskelnerven der hinteren Extremität rufen bei der Reizung ihrer Endapparate wie der Stämme selber einen Beugungsreflex hervor, und zwar erstreckt sich dieser auch auf das gekreuzte Hinterbein. Bei schwächerer Reizung erscheint am gekreuzten Bein eine Streckung.

. Die Hautäste bedürfen einer schwächeren Reizung als die zentripetalen Muskelnerven, um einen Reflex hervorzurufen.

. Die reflektorischen Wirkungen der sensiblen Hautnerven und der zentripetalen Muskelnerven können sich summieren.

. Bei allmählich zunehmender Intensität der Reizung rufen die zentripetalen Muskelnerven am gemischten Muskel (M. quadriceps) bei schwacher Reizung Erschlaffung der Strecker mit verhältnismäßig kurzer Latenzdauer hervor; eine etwas stärkere Reizung gibt zuerst Erschlaffung der Strecker und nachher, mit einer längeren Latenzdauer, Kontraktion der Beuger.

. Bei der Reizung der Hautnerven kommt nur die Kontraktion der Beuger zum Vorschein.

. Die Reflexbahn der zentripetalen Muskelnerven ermüdet schneller und vollständiger als die der Hautnerven, welche viel langsamer ermüdet und bei eintretender Ermüdung in bestimmten Zwischenzeiten bei der wiederholten Reizung reagiert.

. Der Extensortonus im Zustande der azerebralen Rigidität ist beim Kaninchen nur schwach ausgebildet.
Über die Ausscheidung des Alkohols mit der Exspirationsluft1
Authors: Liljestrand G. , Linde P.
Published: April 2012

Nach Alkoholkonsumtion ist der Alkoholgehalt des arteriellen, venösen und kapillaren Blutes praktisch identisch.

Für die Verteilung des Alkohols zwischen Luft und Blut wurde bei 37° Werte zwischen 0.00063 und 0.00073 gefunden, bei Gleichgewicht bei 31° enthält 1 ccm Blut etwa ebensoviel Alkohol wie 2 Liter Luft.

Alveolarluftproben (ad modum Haldane) zeigen in den ersten Stunden nach der Alkoholkonsumtion oft erheblich höhere Alkoholwerte, als nach den Verteilungskoeffizienten zu erwarten ist. Dies beruht auf Beimischung von Luft aus dem Ventrikel, wie sich durch einen Vergleich mit Versuchen mit besonders vorsichtiger Pressung bei der Ausatmung, mit artifizieller Ausdehnung des Ventrikels (Brausepulver) und mit raktaler Alkoholzufuhr herausstellte.

Die Atemluft wird bei der Exspiration abgekühlt, deshalb dürfte der Alkoholgehalt der Alveolarluft auch abnehmen, und man findet für die Alvcolarluft beinahe denselben Alkoholgehalt wie für die Exspirationsluft. Für die Exspirationsluft war der Alkoholgehalt, innerhalb der untersuchten Grenzen, von der Atemtiefe unabhängig, entsprechend einer Sättigung bei 31°. Auch die Luft des schädlichen Raumes dürfte praktisch genommen mit Alkohol bei dieser Temperatur und demselben Druch, wie für die Alveolarluft, gesättigt werden. Für praktische Zwecke läßt sich der Alkoholgehalt der Exspirationsluft gut als Maß für den Alkoholgehalt der Körperflüssigkeiten benutzen.

Während bei neidrigem Alkoholgehalt des Körpers und niedriger Ventilation nur sehr kleine Mengen des resorbierten Alkohols mit der Exspirationsluft ausgeschieden werden, können relativ erhebliche Quantitäten in dieser Weise abgegeben werden, wenn der Alkoholgehalt mäßig und die Ventilation kräftig ist.
Fliegeruntersuchungen
Authors: Christensen E. Hohwü , Krogh August
Published: April 2012

Etwa 50 Vpn wurden mit Hilfe des früher beschriebenen Rebreather‐Verfahrens geprüft. Die individuellen Unterschiede waren groß. Die besten Vpn. konnten auf 6% O2 (45 mm) in der Inspirationsluft herabgehen, während andere schon bei etwa 9% O2 (68 mm) so starke Zeichen von Anoxämie darboten, daß die Prüfung beendet werden mußte. Von 47 geprüften Fliegern haben wir die verschiedenen Werte für die 6 besten (Gruppe A), d. h. denjenigen, die die niedrigsten Sauerstoffwerte in der Inspirationsluft erreicht haben, und für die 6 schlechtesten (Gruppe B) zusammengestellt und verglichen.

In bezug auf Puls und Blutdruck zeigen die beiden Gruppen keine prinzipiellen Unterschiede. Der Unterschied tritt aber sehr deutlich hervor, wenn man die respiratorischen Funktionen vergleicht.

Gruppe A hat von Anfang an eine größere Respirationstiefe als Gruppe B; bei niedrigem O2‐Druck wurde dieser Unterschied stark vergrößert; Gruppe A hat bei niedrigem O2‐Druck eine Respirationstiefe, die 110% größer als die der Gruppe B ist. Die Ventilation ist für Gruppe A bei niedrigem O2‐Druck 65% größer als für B; die alveolare Ventilation ist für Gruppe A auf 14.4 Liter angestiegen, verglichen mit 7.6 Liter für Gruppe B.

Die größere Ventilation für Gruppe A bedingt eine geringe O2‐Differenz zwischen inspirierter und expirierter Luft; diese Differenz ist für Gruppe A 1.87%, dagegen für Gruppe B 3.76%.

Berechnen wir die Zusammensetzung der Alveolarluft nach Bohr, so sehen wir, daß beide Gruppen annähernd die gleiche alveolare O2‐Spannung hatten, wenn der Versuch beendet werden mußte; trotzdem zeigen sie eine Differenz von nicht weniger als 3.02% O2 in der Inspirationsluft. Der kritische O2‐Druck scheint für alle bei einer alveolaren O2‐Spannung von etwa 35 mm Hg zu liegen.

Der prinzipielle Unterschied zwischen den beiden Gruppen muß in der verschieden großen Ventilation gesucht werden, und dieser muß wieder als Ausdruck verschieden großer Reizbarkeit des Atemzentrums genommen werden.

Als Resultat unserer Untersuchung an Fliegern werden wir folgende Forderungen als passend ansehen:

Der Flieger muß ohne ernste Zeichen von Anoxämie bei den Rebreather‐Prüfungen auf einen O2‐Druck in der Inspirationsluft von etwa 60 mm Hg herabgehen können, oder in der Unterdruckkammer bei einem Druck von 360 mm Hg, was einer Höhe von 6 km entspricht sich etwa 10 Minuten lang aufhalten können.
Silber als stimulierendes Mittel bei den Oxidationsprozessen in einem Samenextrakt von Trifolium pratense1
Authors: Thunberg Torsten
Published: April 2012

Silbernitrat und Silbersulfat üben in einer Konzentration von einem Teil Silbersalz auf 150000 Teile Reaktionsmischung eine ausgeprägt stimulierende Wirkung auf die Oxydationserscheinungen in einem Phosphatextrakt aus Samen von Trifolium pratense aus, wie diese in der Entfärbungsgeschwindigkeit eines demselben zugesetzten »Redoxindikators« gemessen werden.
Zur Kenntnis der Urethanempfindlichkeit der Samendehydrogenasen1
Authors: Thunberg T.
Published: April 2012

Verf. teilt eine vergleichende Untersuchung über den Einfluß von Urethanen auf Dehydrogenasensysteme aus Samen von Pisum sativum und Cucumis sativus mit. Sämtliche Urethane wirken hemmend, und der Hemmungseffekt wird um so stärker, je höher man in der homologen Reihe kommt. Folgende Urethane sind untersucht worden: Methylurethan, Äthylurethan, Propylurethan, i‐Butylurethan und i‐Amylurethan. Die hemmende Wirkung macht sich an allen untersuchten Dehydrogenasensystemen geltend, nämlich an den auf folgende Donatoren eingestellten: Äthylalkohol, Hexosediphosphorsäure, Apfelsäure, Glutaminsäure und Zitronensäure. Verschiedene Dehydrogenasensysteme sind indessen verschieden stark empfindlich. Am empfindlichsten scheint das Enzymsystem zu sein, das Alkohol als Donator gebraucht. — Ferner werden auch Hemmungskurven für Chloralhydrat, Diäthylmalonylcarbamid und Hedonal mitgeteilt.

Nordisk Insulinfond sage ich für die Bereitstellung von Mitteln für die Durchführung dieser Untersuchungen meinen Dank.