Isometric rate of force development, maximum voluntary contraction, and balance in women with and without joint hypermobility

OBJECTIVE: To determine differences between hypermobile subjects and controls in terms of maximum strength, rate of force development, and balance. METHODS: We recruited 13 subjects with hypermobility and 18 controls. Rate of force development and maximal voluntary contraction (MVC) during single leg knee extension of the right knee were measured isometrically for each subject. Balance was tested twice on a force plate with 15-second single-leg stands on the right leg. Rate of force development (N/second) and MVC (N) were extracted from the force-time curve as maximal rate of force development (= limit Deltaforce/Deltatime) and the absolute maximal value, respectively. RESULTS: The hypermobile subjects showed a significantly higher value for rate of force development (15.2% higher; P = 0.038, P = 0.453, epsilon = 0.693) and rate of force development related to body weight (16.4% higher; P = 0.018, P = 0.601, epsilon = 0.834) than the controls. The groups did not differ significantly in MVC (P = 0.767, P = 0.136, epsilon = 0.065), and MVC related to body weight varied randomly between the groups (P = 0.921, P = 0.050, epsilon = 0.000). In balance testing, the mediolateral sway of the hypermobile subjects showed significantly higher values (11.6% higher; P = 0.034, P = 0.050, epsilon = 0.000) than that of controls, but there was no significant difference (4.9% difference; P = 0.953, P = 0.050, epsilon = 0.000) in anteroposterior sway between the 2 groups. CONCLUSION: Hypermobile women without acute symptoms or limitations in activities of daily life have a higher rate of force development in the knee extensors and a higher mediolateral sway than controls with normal joint mobility.

Origin of renal myofibroblasts in the model of unilateral ureter obstruction in the rat

Tubulo-interstitial fibrosis is a constant feature of chronic renal failure and it is suspected to contribute importantly to the deterioration of renal function. In the fibrotic kidney there exists, besides normal fibroblasts, a large population of myofibroblasts, which are supposedly responsible for the increased production of intercellular matrix. It has been proposed that myofibroblasts in chronic renal failure originate from the transformation of tubular cells via epithelial-mesenchymal transition (EMT) or from infiltration by bone marrow-derived precursors. Little attention has been paid to the possibility of a transformation of resident fibroblasts into myofibroblasts in renal fibrosis. Therefore we examined the fate of resident fibroblasts in the initial phase of renal fibrosis in the classical model of unilateral ureter obstruction (UUO) in the rat. Rats were perfusion-fixed on days 1, 2, 3 and 4 after ligature of the right ureter. Starting from 1 day of UUO an increasing expression of alpha-smooth muscle actin (alphaSMA) in resident fibroblasts was revealed by immunofluorescence and confirmed by the observation of bundles of microfilaments and webs of intermediate filaments in the electron microscope. Inversely, there was a decreased expression of 5'-nucleotidase (5'NT), a marker of renal cortical fibroblasts. The RER became more voluminous, suggesting an increased synthesis of matrix. Intercellular junctions, a characteristic feature of myofibroblasts, became more frequent. The mitotic activity in fibroblasts was strongly increased. Renal tubules underwent severe regressive changes but the cells retained their epithelial characteristics and there was no sign of EMT. In conclusion, after ureter ligature, resident peritubular fibroblasts proliferated and they showed progressive alterations, suggesting a transformation in myofibroblasts. Thus the resident fibroblasts likely play a central role in fibrosis in that model.

Interhemispheric balance of overt attention: a theta burst stimulation study

Interhemispheric imbalance is discussed as a pathophysiological mechanism in visuospatial neglect. It is suggested that after a lesion of the right hemisphere the mutual transcallosal inhibition is impaired, resulting in an increased activity of the left hemisphere. We investigated the interhemispheric balance of attention in healthy subjects by using a free visual exploration task and by interfering with the neural activity of the posterior parietal cortex (PPC) of either hemisphere using an inhibitory transcranial magnetic stimulation routine with theta burst stimulation (TBS). Subjects explored colour photographs of real-life scenes presented on a computer screen under four conditions: (i) without TBS; (ii) after TBS over the right PPC; (iii) after TBS over the left PPC; and (iv) after TBS over the right PPC and, after the first half of the task, over the left PPC. Eye movements were measured, and distribution of mean cumulative fixation duration over screen halves was analyzed. TBS over the right PPC resulted in a significant rightward shift of mean cumulative fixation duration of approximately 30 min. The shift could be reversed when a subsequent train of TBS was applied over the left PPC. However, left PPC stimulation alone had no significant effect on visual exploration behaviour. The present study shows that the effect of TBS on the PPC depends on which hemisphere is stimulated and on the state of the contralateral homologue area. These findings are in accordance with the predictions of the interhemispheric rivalry model in neglect.

Allocentric and egocentric spatial impairments in a case of topographical disorientation

We describe a patient with a topographical disorientation after a stroke of the right mediotemporooccipital lobe including the parahippocampal cortex (PHC). Clinical observations and neuropsychological testing reveal an impairment of allocentric spatial representations as well as impairments of visuospatial learning and memory. These findings are in accordance with the well-known function of the PHC in topographical disorientation. As a new finding, results from oculomotor tasks show additional impairments of the egocentric spatial coordinate frame suggesting that in topographical disorientation due to a lesion of the right mediotemporooccipital lobe not only allocentric but also egocentric visuospatial functions are disturbed.

The role of the human posterior parietal cortex in memory-guided saccade execution: a double-pulse transcranial magnetic stimulation study

The present study investigated the role of the right posterior parietal cortex (PPC) in the triggering of memory-guided saccades by means of double-pulse transcranial magnetic stimulation (dTMS). Shortly before saccade onset, dTMS with different interstimulus intervals (ISI; 35, 50, 65 or 80 ms) was applied. For contralateral saccades, dTMS significantly decreased saccadic latency with an ISI of 80 ms and increased saccadic gain with an ISI of 65 and 80 ms. Together with the findings of a previous study during frontal eye field (FEF) stimulation the present results demonstrate similarities and differences between both regions in the execution of memory-guided saccades. Firstly, dTMS facilitates saccade triggering in both regions, but the timing is different. Secondly, dTMS over the PPC provokes a hypermetria of contralateral memory-guided saccades that was not observed during FEF stimulation. The results are discussed within the context of recent neurophysiological findings in monkeys.

Visualization of alveolar recruitment in a porcine model of unilateral lung lavage using 3He-MRI

BACKGROUND: In the acute respiratory distress syndrome potentially recruitable lung volume is currently discussed. (3)He-magnetic resonance imaging ((3)He-MRI) offers the possibility to visualize alveolar recruitment directly. METHODS: With the approval of the state animal care committee, unilateral lung damage was induced in seven anesthetized pigs by saline lavage of the right lungs. The left lung served as an intraindividual control (healthy lung). Unilateral lung damage was confirmed by conventional proton MRI and spiral-CT scanning. The total aerated lung volume was determined both at a positive end-expiratory pressure (PEEP) of 0 and 10 mbar from three-dimensionally reconstructed (3)He images, both for healthy and damaged lungs. The fractional increase of aerated volume in damaged and healthy lungs, followed by a PEEP increase from 0 to 10 mbar, was compared. RESULTS: Aerated gas space was visualized with a high spatial resolution in the three-dimensionally reconstructed (3)He-MR images, and aeration defects in the lavaged lung matched the regional distribution of atelectasis in proton MRI. After recruitment and PEEP increase, the aerated volume increased significantly both in healthy lungs from 415 ml [270-445] (median [min-max]) to 481 ml [347-523] and in lavaged lungs from 264 ml [71-424] to 424 ml [129-520]. The fractional increase in lavaged lungs was significantly larger than that in healthy lungs (healthy: 17% [11-38] vs. lavage: 42% [14-90] (P=0.031). CONCLUSION: The (3)He-MRI signal might offer an experimental approach to discriminate atelectatic vs. poor aerated lung areas in a lung damage animal model. Our results confirm the presence of potential recruitable lung volume by either alveolar collapse or alveolar flooding, in accordance with previous reports by computed tomography.

Induction of complete and sustained remission of rheumatoid pachymeningitis by rituximab

Aseptic pachymeningitis is a rare and serious complication of rheumatoid arthritis (RA). Herein, we describe a patient with rheumatoid factor-positive and anti-cyclic citrullinated peptide-positive RA who experienced a focal seizure, with aphasia and convulsions of the right side of the body. The findings of magnetic resonance imaging and histologic analysis led to a diagnosis of rheumatoid pachymeningitis. Because the patient had a large number of CD20-expressing B lymphocytes, therapy with rituximab was started and has resulted in complete and sustained remission of both the pachymeningitis and the RA for >2 years. Despite a decrease in immunoglobulins, the patient has remained free of infections, which illustrates the favorable outcome that can result from therapeutic B cell depletion in this potentially lethal manifestation of RA.

Erythropoietin enhances oxygenation in critically perfused tissue through modulation of nitric oxide synthase

The aim of this study was to investigate the effect of human recombinant erythropoietin (EPO) on the microcirculation and oxygenation of critically ischemic tissue and to elucidate the role of endothelial NO synthase in EPO-mediated tissue protection. Island flaps were dissected from the back skin of anesthetized male Syrian golden hamsters including a critically ischemic, hypoxic area that was perfused via a collateralized vasculature. Before ischemia, animals received an injection of epoetin beta at a dose of 5,000 U/kg body weight with (n = 7) or without (n = 7) blocking NO synthase by 30 mg/kg body weight L-NAME (Nomega-nitro-L-arginine methyl ester hydrochloride). Saline-treated animals served as control (n = 7). Ischemic tissue damage was characterized by severe hypoperfusion and inflammation, hypoxia, and accumulation of apoptotic cell nuclei after 5 h of collateralization. Erythropoietin pretreatment increased arteriolar and venular blood flow by 33% and 37%, respectively (P < 0.05), and attenuated leukocytic inflammation by approximately 75% (P < 0.05). Furthermore, partial tissue oxygen tension in the ischemic tissue increased from 8.2 to 15.8 mmHg (P < 0.05), which was paralleled by a 21% increased density of patent capillaries (P < 0.05) and a 50% reduced apoptotic cell count (P < 0.05). The improved microcirculation and oxygenation were associated with a 2.2-fold (P < 0.05) increase of endothelial NO synthase protein expression. Of interest, L-NAME completely abolished all the beneficial effects of EPO pretreatment. Our study demonstrates that, in critically ischemic and hypoxic collateralized tissue, EPO pretreatment improves tissue perfusion and oxygenation in vivo. This effect may be attributed to NO-dependent vasodilative effects and anti-inflammatory actions on the altered vascular endothelium.

Virtopsy: forensic traumatology of the subcutaneous fatty tissue; multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) as diagnostic tools

Traumatic lesions of the subcutaneous fatty tissue provide important clues for forensic reconstruction. The interpretation of these patterns requires a precise description and recording of the position and extent of each lesion. During conventional autopsy, this evaluation is performed by dissecting the skin and subcutaneous tissues in successive layers. In this way, depending on the force and type of impact (right angle or tangent), several morphologically distinct stages of fatty tissue damage can be differentiated: perilobular hemorrhage (I), contusion (II), or disintegration (III) of the fat lobuli, and disintegration with development of a subcutaneous cavity (IV). In examples of virtopsy cases showing blunt trauma to the skin and fatty tissue, we analyzed whether these lesions can also be recorded and classified using multislice computed tomography (MSCT) and magnetic resonance imaging (MRI). MSCT has proven to be a valuable screening method to detect the lesions, but MRI is necessary in order to properly differentiate and classify the grade of damage. These noninvasive radiological diagnostic tools can be further developed to play an important role in forensic examinations, in particular when it comes to evaluating living trauma victims.

Better conduct of clinical trials: the control group in critical care trials

OBJECTIVE: To review trial design issues related to control groups. DESIGN: Review of the literature with specific reference to critical care trials. MAIN RESULTS AND CONCLUSIONS: Performing randomized controlled trials in the critical care setting presents specific problems: studies include patients with rapidly lethal conditions, the majority of intensive care patients suffer from syndromes rather than from well-definable diseases, the severity of such syndromes cannot be precisely assessed, and the treatment consists of interacting therapies. Interactions between physiology, pathophysiology, and therapies are at best marginally understood and may have a major impact on study design and interpretation of results. Selection of the right control group is crucial for the interpretation and clinical implementation of results. Studies comparing new interventions with current ones or different levels of current treatments have the problem of the necessity of defining "usual care." Usual care controls without any constraints typically include substantial heterogeneity. Constraints in the usual therapy may help to reduce some variation. Inclusion of unrestricted usual care groups may help to enhance safety. Practice misalignment is a novel problem in which patients receive a treatment that is the direct opposite of usual care, and occurs when fixed-dose interventions are used in situations where care is normally titrated. Practice misalignment should be considered in the design and interpretation of studies on titrated therapies.

Assigning Bug Reports using a Vocabulary-Based Expertise Model of Developers

For popular software systems, the number of daily submitted bug reports is high. Triaging these incoming reports is a time consuming task. Part of the bug triage is the assignment of a report to a developer with the appropriate expertise. In this paper, we present an approach to automatically suggest developers who have the appropriate expertise for handling a bug report. We model developer expertise using the vocabulary found in their source code contributions and compare this vocabulary to the vocabulary of bug reports. We evaluate our approach by comparing the suggested experts to the persons who eventually worked on the bug. Using eight years of Eclipse development as a case study, we achieve 33.6\% top-1 precision and 71.0\% top-10 recall.

[Fever of unknown origin as a sign of calcium pyrophosphate deposition disease]

Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease may manifest clinically as septic fever (40 degrees C), acute pseudogout attack of knee, wrist and shoulders, or as a variety of patterns of chronic inflammatory or degenerative joint disease. The association of pseudogout with fever is less widely recognised and may lead to over-investigation, delay in appropriate treatment and disproportionate costs. We report on a 67-year-old woman with a history of recurrent episodes of fever and polyarthritis every 2 months for the last 3 years. Because of this she was hospitalised several times, finally with suspected culture-negative endocarditis, and was treated for 6 weeks with gentamicin, rifampicin and vancomycin. During this therapy the patient again developed septic fever and acute arthritis of the right wrist. Radiographs of the wrist, knee and symphysis pubis revealed prominent chondrocalcinosis and destructive arthropathy.

Controversies of fetal cardiac intervention

Remarkable advances in ultrasound imaging technology have made it possible to diagnose fetal cardiovascular lesions as early as 12-14 weeks of gestation and to assess their physiological relevance by echocardiography. Moreover, invasive techniques have been developed and refined to relieve significant congenital heart disease (CHD), such as critical aortic and pulmonary stenoses in the pediatric population including neonates. Recognition of the fact that certain CHDs can evolve in utero, and early intervention may improve the outcome by altering the natural history of such conditions has led to the evolution of a new fetal therapy, i.e. fetal cardiac intervention. Two entities, pulmonary valvar atresia and intact ventricular septum (PA/IVS) and hypoplastic left heart syndrome (HLHS), are associated with significant morbidity and mortality even with postnatal surgical therapy. These cases are believed to occur due to restricted blood flow, leading to impaired growth and function of the right or left ventricle. Therefore, several centers started the approach of antenatal intervention with the primary goal of improving the blood flow through the stenotic/atretic valve orifices to allow growth of cardiac structures. Even though centers with a reasonable number of cases seem to have improved the technique and the immediate outcome of fetal interventions, the field is challenged by ethical issues as the intervention puts both the mother and the fetus at risk. Moreover, the perceived benefits of prenatal treatment have to be weighed against steadily improving postnatal surgical and hybrid procedures, which have been shown to reduce morbidity and mortality for these complex heart defects. This review is an attempt to provide a balanced opinion and an update on fetal cardiac intervention.

Electrocardiographic pattern as a guide for management and radiofrequency ablation of idiopathic ventricular tachycardia.

BACKGROUND Idiopathic ventricular tachycardia (VT) often originates from the right ventricular outflow tract (RVOT), but foci deep to the endocardium, in the epicardium, or in the left ventricle are not uncommon. Although these extra-RVOT foci can be targeted with ablation, risks involved are higher and success rates lower. Simple electrocardiographic (ECG) criteria allowing (1) discrimination of RVOT foci from extra-RVOT foci and (2) assessment of the chance of success of a right heart ablation procedure are desirable. METHODS Twenty-five consecutive patients referred for radiofrequency (RF) ablation of idiopathic VT or severely symptomatic idiopathic ventricular premature contractions were included. Localization of VT origin and success rates of VT ablation in the RVOT were analyzed according to the ECG pattern. RESULTS The analysis of the R wave in V2 was the strongest single predictor of whether the VT had an RVOT or an extra-RVOT origin. An R wave amplitude < or =30% of the QRS amplitude designated the VT focus in the RVOT with positive and negative predictive values of 95 and 100%, respectively. Analysis of R wave duration in V2 had similar predictive values, whereas the R/S transition zone in precordial leads had slightly lower predictive values. Seventeen of 20 arrhythmias (85%) with an R wave amplitude < or =30% of the QRS amplitude in V2 could be successfully abolished by an exclusively right heart procedure. CONCLUSIONS The analysis of ECG pattern makes it possible to guide the management of patients with idiopathic VT in predicting the arrhythmias that can be safely targeted with RF ablation from the RVOT with high success rates.

True aneurysm of the peripheral pulmonary artery due to necrotizing giant cell arteritis

Pulmonary artery aneurysm in adults is a rare diagnosis. Most cases described in the literature are either associated with congenital heart disease or pulmonal arterial hypertension, respectively, or are not true aneurysms but rather pseudoaneurysms, which are usually iatrogenic. We present the case of a 68-year old female patient with the incidental finding of a true aneurysm of the right peripheral pulmonary artery with a maximum diameter of 4 cm. With increasing aneurysm diameter over time, the decision for a surgical resection was made. Complete resection of the aneurysm including lower lobe resection was performed. Histopathological examination showed necrotizing giant cell arteritis as the underlying cause. The postoperative course was uneventful and no signs of further disease activity were detected. To our knowledge, this is the first reported case of a pulmonary artery aneurysm caused by giant cell arteritis, whereas it should be noted that the distinction between Takayasu arteritis and giant cell arteritis is not clearly defined. Considering the high mortality associated with aneurysm rupture, surveillance is advocated for small aneurysms, whereas for larger aneurysms and those showing signs of progression in size despite medical therapy or even dissection, surgical intervention should be considered.