Cardiac MRI findings to differentiate athlete's heart from hypertrophic (HCM), arrhythmogenic right ventricular (ARVC) and dilated (DCM) cardiomyopathy.

To provide clinically relevant criteria for differentiation between the athlete's heart and similar appearing hypertrophic (HCM), dilated (DCM), and arrhythmogenic right-ventricular cardiomyopathy (ARVC) in MRI. 40 top-level athletes were prospectively examined with cardiac MR (CMR) in two university centres and compared to retrospectively recruited patients diagnosed with HCM (n = 14), ARVC (n = 18), and DCM (n = 48). Analysed MR imaging parameters in the whole study cohort included morphology, functional parameters and late gadolinium enhancement (LGE). Mean left-ventricular enddiastolic volume index (LVEDVI) was high in athletes (105 ml/m2) but significantly lower compared to DCM (132 ml/m2; p = 0.001). Mean LV ejection fraction (EF) was 61% in athletes, below normal in 7 (18%) athletes vs. EF 29% in DCM, below normal in 46 (96%) patients (p < 0.0001). Mean RV-EF was 54% in athletes vs. 60% in HCM, 46% in ARVC, and 41% in DCM (p < 0.0001). Mean interventricular myocardial thickness was 10 mm in athletes vs. 12 mm in HCM (p = 0.0005), 9 mm in ARVC, and 9 mm in DCM. LGE was present in 1 (5%) athlete, 8 (57%) HCM, 10 (56%) ARVC, and 21 (44%) DCM patients (p < 0.0001). Healthy athletes' hearts are characterized by both hypertrophy and dilation, low EF of both ventricles at rest, and increased interventricular septal thickness with a low prevalence of LGE. Differentiation of athlete's heart from other non-ischemic cardiomyopathies in MRI can be challenging due to a significant overlap of characteristics also seen in HCM, ARVC, and DCM.

Case report of a cervical myelomalacia caused by a thoracolumbar intradural disc herniation leading to intracranial hypotension.

A 50-year-old patient was admitted with symptoms of intracranial hypotension. MRI revealed a cervical myelomalacia caused by engorged epidural veins leading to a stenosis of the spinal canal. This condition is rarely described in patients with hydrocephalus and ventricular shunts suffering from chronic overdrainage. However, the reason in this patient was a CSF leak caused by an intradural disc herniation at T12/L1. After surgery, symptoms resolved and the cervical myelomalacia and the swollen epidural veins disappeared on postoperative MRI. In patients with engorged cervical epidural veins without a ventricular shunt, a CSF leak has to be considered.

[Instantaneous wave-free ratio (iFR®) in patients with coronary artery disease]. / "Instantaneous wave-free ratio" (iFR®) bei Patienten mit koronarer Herzkrankheit.

Coronary angiography is considered as the gold standard in the morphological representation of coronary artery stenosis. Coronary angiography is often performed without preprocedural non-invasive proof of ischemia and the assessment of the severity of a coronary lesion by morphology is very subjective. Thus, invasive fractional flow reserve (FFR) measurement represents the current standard for estimation of the hemodynamic relevance of coronary artery stenosis and facilitates decision making for percutaneous coronary intervention (PCI) and stenting. The FFR-guided revascularization strategy has been classified as a class IA recommendation in the 2014 ESC/EACTS guidelines on myocardial revascularization. Both the DEFER and the FAME studies showed no treatment advantage of hemodynamically irrelevant stenosis. By use of FFR (and targeted interventions), clinical results could be improved as well as the procedure costs were reduced; however, the use in clinical practice is still limited due to the need of adenosine administration and a significant prolongation of the procedure. Instantaneous wave-free ratio (iFR®) is a new innovative approach for the determination of the hemodynamic relevance of coronary stenosis which can be obtained at rest without the use of vasodilators. Regarding periprocedural complications as well as prognosis, iFR® showed non-inferiority compared to FFR in the SWEDEHEART and DEFINE-FLAIR trials.

Fluorescence-Reported Allelic Exchange Mutagenesis Reveals a Role for Chlamydia trachomatis TmeA in Invasion That Is Independent of Host AHNAK.

Development of approaches to genetically manipulate Chlamydia is fostering important advances in understanding pathogenesis. Fluorescence-reported allelic exchange mutagenesis (FRAEM) now enables the complete deletion of specific genes in C. trachomatis L2. We have leveraged this technology to delete the coding sequences for a known type III effector. The evidence provided here indicates that CT694/CTL0063 is a virulence protein involved in chlamydial invasion. Based on our findings, we designate the gene product corresponding to ct694-ctl0063translocated membrane-associated effector A (TmeA). Deletion of tmeA did not impact development of intracellular chlamydiae. However, the absence of TmeA manifested as a decrease in infectivity in both tissue culture and murine infection models. The in vitro defect was reflected by impaired invasion of host cells. TmeA binds human AHNAK, and we demonstrate here that AHNAK is transiently recruited by invading chlamydiae. TmeA, however, is not required for endogenous AHNAK recruitment. TmeA also impairs AHNAK-dependent actin bundling activity. This TmeA-mediated effect likely does not explain impaired invasion displayed by the tmeA strain of Chlamydia, since AHNAK-deficient cells revealed no invasion phenotype. Overall, our data indicate the efficacy of FRAEM and reveal a role of TmeA during chlamydial invasion that manifests independently of effects on AHNAK.

Fast calcium and voltage-sensitive dye imaging in enteric neurones reveal calcium peaks associated with single action potential discharge.

Slow changes in [Ca(2+)](i) reflect increased neuronal activity. Our study demonstrates that single-trial fast [Ca(2+)](i) imaging (≥200 Hz sampling rate) revealed peaks each of which are associated with single spike discharge recorded by consecutive voltage-sensitive dye (VSD) imaging in enteric neurones and nerve fibres. Fast [Ca(2+)](i) imaging also revealed subthreshold fast excitatory postsynaptic potentials. Nicotine-evoked [Ca(2+)](i) peaks were reduced by -conotoxin and blocked by ruthenium red or tetrodotoxin. Fast [Ca(2+)](i) imaging can be used to directly record single action potentials in enteric neurones. [Ca(2+)](i) peaks required opening of voltage-gated sodium and calcium channels as well as Ca(2+) release from intracellular stores.

HLA-B*9553: a novel HLA allele shown in three generations of a family.

Human leukocyte antigen (HLA)-B*9553, a novel HLA-B allele, was identified in a volunteer hematopoietic stem cell donor. HLA-B*9553 differs from the closely related allele HLA-B*1518 in one single nucleotide substitution resulting in an amino acid substitution.

Cytochrome p450 2C enzymes contribute to peritransplant ischemic injury and cardiac allograft vasculopathy.

Peritransplant ischemia and reperfusion (I/R) injury contributes to posttransplant vascular dysfunction and cardiac allograft vasculopathy (CAV). We have previously shown that cytochrome p450 (CYP) 2C inhibition significantly reduces I/R-induced myocardial infarction and postischemic vascular dysfunction. In the latter study, pretreatment with sulfaphenazole (SP), a specific inhibitor of CYP 2C, restored postischemic NO-mediated, endothelium-dependent vasodilation and reduced vascular superoxide production. Given the association between I/R injury, early vascular dysfunction and CAV, we hypothesized that CYP 2C may also contribute to the onset of CAV. Lewis-to-Fisher rat heterotopic heart transplants were performed. Donors and recipients were treated with 5 mg/kg SP or vehicle control 1 h prior to surgery. SP did not affect posttransplant morbidity, mortality or weight gain. Coronary blood vessels from rats treated with SP exhibited significantly reduced luminal narrowing and demonstrated a corresponding decrease in smooth muscle cell (SMC) proliferation compared to controls. SP did not reduce diffuse, focal, epicardial, endocardial or perivascular immune infiltration nor did it significantly alter TUNEL positivity in myocardial, endothelial or SMC populations. In conclusion, CYP 2C contributes to SMC proliferation CAV without affecting general immune infiltration.

Anti-chromatin and anti-C1q antibodies in systemic lupus erythematosus compared to other systemic autoimmune diseases.

OBJECTIVE: To evaluate the prevalence, sensitivity, and specificity of anti-chromatin and anti-C1q antibodies in systemic lupus erythematosus (SLE) and lupus nephritis compared to small vessel vasculitis and other connective tissue diseases. To provide long-term follow-up data for anti-chromatin antibodies in lupus nephritis. METHODS: We determined the significance of anti-nuclear antibodies (ANA), anti- double-stranded DNA (anti-dsDNA), anti-chromatin, and anti-C1q antibodies, as well as complement factors C3 and C4, in relation to disease activity in SLE patients with (n = 47; long-term follow-up data for 33 patients) and without (n = 31) biopsy-confirmed lupus nephritis, microscopic polyangiitis (n = 37), Wegener's granulomatosis (n = 66), primary Sjögren's syndrome (n = 17), limited scleroderma (CREST syndrome) (n = 6), and progressive systemic scleroderma (PSS) (n = 11). RESULTS: Anti-chromatin antibodies were more specific and sensitive than anti-C1q antibodies in distinguishing SLE patients from those with other systemic autoimmune diseases [anti-chromatin: sensitivity 64.1%, specificity 99.2%, odds ratio (OR) 219.6; anti-C1q: sensitivity 50%, specificity 72.6%, OR 2.65]. Anti-C1q antibodies were present in 75% of patients with Sjögren's syndrome and 35.1% of patients with microscopic polyangiitis. Anti-chromatin antibodies could identify SLE in patients with positive ANA but negative anti-dsDNA antibodies. Persisting anti-chromatin antibodies indicated SLE disease activity, even if anti-dsDNA antibodies had become negative. In long-term follow-up, those SLE patients with negative anti-dsDNA antibodies but persisting ANA and anti-chromatin antibodies relapsed if immunosuppression had been tapered. Anti-chromatin antibodies correlated with the SLE disease activity index (SLEDAI) as a marker of disease activity. CONCLUSIONS: The measurement of anti-chromatin, but not anti-C1q, antibodies in patients with systemic autoimmune diseases increases diagnostic sensitivity and specificity for SLE and assists in treatment decisions in anti-dsDNA-negative patients.

Tuberculosis screening of asylum seekers: 1 years' experience at the Dover Induction Centres.

OBJECTIVES: To describe the uptake and outcomes of a service for tuberculosis screening of asylum seekers. STUDY DESIGN: Descriptive study. METHODS: A tuberculosis screening service was established at the Dover Induction Centres for all asylum seekers entering the UK through ports in Kent. This study describes the uptake and completion of tuberculosis screening, the results of tuberculin skin testing and follow-up, and the cost of the service during its first year. RESULTS: In 1 year, 8258 asylum seekers were screened: 94% of 8799 who were eligible. A total of 2.2% of those with completed screens were positive (on the basis of symptoms requiring further investigation or positive Heaf reaction). Eleven cases of active respiratory disease were diagnosed on the basis of symptoms, Heaf reaction plus chest X-ray, or both; three were confirmed microbiologically. One-quarter of Heaf tests were not read because of the rapid dispersal of asylum seekers. The follow-up of those requiring further investigations at their destinations was largely unknown. The service cost was 350,000 pounds. CONCLUSIONS: Induction centre tuberculosis screening services for asylum seekers can achieve a high uptake, but their cost-effectiveness is questionable, particularly where the yield of active disease is low. Tuberculin skin testing is not an ideal screening procedure in this setting because it may be uncompleted and the benefit of detecting latent infections is uncertain.

Pulmonary sarcoidosis in a 14-year-old boy diagnosed by low-dose CT-guided transthoracic lung biopsy.

Pulmonary sarcoidosis is a rare disease in the pediatric age group, characterized by the presence of epitheloid-cell granulomas. In stage 3 sarcoidosis, pulmonary infiltrates without hilar lymphadenopathy occur. Definitive diagnosis requires a histopathological specimen, which might be difficult to obtain by transbronchial biopsy. Multidetector computed tomography (MDCT)-guided transthoracic lung biopsy (TLB) is a well-established procedure in adults, but has only rarely been applied in children.A 14-year-old boy was admitted to hospital for evaluation of a chronic systemic disease with severe pulmonary manifestation. All investigations, including bronchosopy and bronchoalveolar lavage with microbiological and virological testing, had been negative. MDCT-guided TLB was performed on a 16-section scanner with a low-dose protocol (single slices, 120 kV, 20 mAs), using a 16-gauge biopsy device. The total effective dose was 0.4 mSv for the biopsy procedure. Histopathological examination revealed multiple epitheloid-cell granulomas with giant cells in the absence of microbiological or virological abnormalities. A diagnosis of stage 3 pulmonary sarcoidosis was made and systemic anti-inflammatory therapy was administered, which led to complete remission within weeks. MDCT-guided TLB can be a valuable instrument in assessing pulmonary manifestations of pediatric sarcoidosis, enabling precise histopathological diagnosis and adequate therapy. The use of low-dose protocols can substantially reduce radiation exposure without relevant loss of image information. MDCT-guided lung biopsy should be considered prior to open-lung surgery in selected patients with unclear pulmonary disease.

A novel flexible, retrievable endovascular stent system for small-vessel anatomy: preliminary in vivo data.

BACKGROUND AND PURPOSE: This study assessed the in vivo delivery, retrievability, short-term patency, and cellular response to a new flexible endovascular stent system in a rabbit model. The stent is designed for delivery through a microcatheter and is fully retrievable with electrolytic detachment from a delivery wire. METHODS: We successfully deployed nine stents (range of sizes, 2.5-4 mm diameter, 15-35 mm length) in six straight (carotid) and three angled (subclavian) arteries of six Chinchilla Bastard rabbits. Serial imaging was performed by using intravenous digital subtraction angiography (IVDSA), contrast-enhanced MR angiography (CEMRA), time-of-flight MR angiography (TOF), and CT-angiography 3 days and 4 weeks after stent deployment. Subjects were euthenized after 4 weeks (n = 5), and stents were removed for histologic analysis. RESULTS: Stent deployment was feasible in all cases. After initial deployment, all stents could be fully retrieved within the microcatheter. The detachment zone and the distal stent marker were easily visible under fluoroscopy, and final detachment occurred reliably in all cases. We observed no procedural complications. Noninvasive imaging by using IVDSA, MR angiography, and CT angiography was feasible in this stent system and demonstrated all arteries patent and not narrowed at 3 days and 4 weeks, findings that were confirmed by histologic analysis. CONCLUSION: This electrolytically detachable stent is promising as a treatment for intracranial arteries, because it can be delivered through microcatheters small enough for intracranial navigation. It is fully retrievable, thus providing greater control than currently available stents. Noninvasive imaging by using IVDSA, MR angiography, and CT angiography is feasible in this stent system and may be useful for follow-up. Further long-term data are needed.

[Stress and autonomic dysregulation in patients with fibromyalgia syndrome]. / Stress und autonome Dysregulation bei Patienten mit einem Fibromyalgiesyndrom.

AIM: The aim of the present study was to evaluate to what extent the orthostatic dysregulation of FMS patients can be attributed primarily to reduced baroreceptor-mediated activation of the sympathetic nervous system and whether a hyporeactive sympathetic nervous system can also be confirmed for mental stress. PATIENTS AND METHODS: A total of 28 patients with primary FMS were examined and compared with 15 healthy subjects. Diagnostic investigations of the autonomic nervous system were based on measuring HRV in frequency range and assessing spontaneous baroreflex sensitivity (sBRS) under mental stress and passive orthostatism. RESULTS: Both under orthostatic and mental stress FMS patients exhibited reduced activation of the sympathetic nervous system as measured by the spectral power of HRV in the low-frequency range and the mean arterial blood pressure or heart rate. The present study provided no indications for dysregulation of sBRS. CONCLUSION: The results obtained confirm the hypothesis of a hyporeactive stress system in FMS patients for both peripherally and centrally mediated stimulation of the sympathetic nervous system.

Improved clinical outcome of lupus nephritis during the past decade: importance of early diagnosis and treatment.

OBJECTIVE: To evaluate the differences in the outcome of lupus nephritis diagnosed either in the 1980s or the 1990s in Heidelberg, Germany. METHODS: Fifteen patients with biopsy confirmed lupus nephritis (LN) were followed up between 1980 and 1989 and 41 patients were followed up between 1990 and 2000. Their status at diagnosis and their treatment schedules and outcome were analysed. 68% had WHO IV nephritis. RESULTS: In the decade from 1990 to 2000 there was significantly less proteinuria (46 v 17 g/l, p=0.008), significantly lower rates of renal failure (40% v 17%, p=0.02), and fewer histological signs of chronicity (33% v 10%, p=0.01) at the time of diagnosis of LN than in the decade from 1980 to 1989. The mean (SD) time from the first appearance of proteinuria until kidney biopsy was significantly shorter in the later decade (15.4 (15.6) v 3.9 (4.7) months). Although treatment schedules were not significantly different, the outcome of the disease was significantly better in the patients who were diagnosed with LN between 1990 and 2000 (p=0.045). Whereas 6/15 (40%) patients between 1980 and 1989 had terminal renal failure after a mean time of 94 months, in the group of 1990-2000 no patient developed terminal renal failure (median observation time 24 months). In both groups one patient died from infection. A high chronicity index in histology and the presence of arterial hypertension or renal failure, or both, at the time of diagnosis were significant risk factors for the development of terminal renal failure in the course of the disease. CONCLUSIONS: The outcome of patients with newly diagnosed LN was significantly better between 1990 and 2000 than between 1980 and 1989. Kidney damage and chronic histological changes at time of diagnosis were significantly less common between 1990 and 2000, which is attributable to earlier diagnosis and treatment in the later decade.

Cone-beam CT with megavoltage beams and an amorphous silicon electronic portal imaging device: potential for verification of radiotherapy of lung cancer.

We investigate the potential of megavoltage (MV) cone-beam CT with an amorphous silicon electronic portal imaging device (EPID) as a tool for patient position verification and tumor/organ motion studies in radiation treatment of lung tumors. We acquire 25 to 200 projection images using a 22 x 29 cm EPID. The acquisition is automatic and requires 7 minutes for 100 projections; it can be synchronized with respiratory gating. From these images, volumetric reconstruction is accomplished with a filtered backprojection in the cone-beam geometry. Several important prereconstruction image corrections, such as detector sag, must be applied. Tests with a contrast phantom indicate that differences in electron density of 2% can be detected with 100 projections, 200 cGy total dose. The contrast-to-noise ratio improves as the number of projections is increased. With 50 projections (100 cGy), high contrast objects are visible, and as few as 25 projections yield images with discernible features. We identify a technique of acquiring projection images with conformal beam apertures, shaped by a multileaf collimator, to reduce the dose to surrounding normal tissue. Tests of this technique on an anthropomorphic phantom demonstrate that a gross tumor volume in the lung can be accurately localized in three dimensions with scans using 88 monitor units. As such, conformal megavoltage cone-beam CT can provide three-dimensional imaging of lung tumors and may be used, for example, in verifying respiratory gated treatments.

Complications of lesser toe surgery.

Surgical procedures for lesser toe problems are among the most common surgeries done on the foot. In a shoe wearing population, the incidence of lesser toe pathologic disorders is high. The complications associated with lesser toe surgery can be troublesome for patients and physicians. Understanding the possible common complications and how to avoid them is essential to maximizing satisfactory clinical results.

Improvement in early detection of congenital hearing impairment due to universal newborn hearing screening.

OBJECTIVE: The aim of this study was to determine whether universal newborn hearing screening (UNHS) is effective in increasing the number of children whose hearing impairment is detected early, i.e. within the first 6 months of life. It also investigated whether UNHS contributes most to the early detection of moderately and severely hearing-impaired newborns, as suggested by a recently published report. METHODS: The study consisted of a retrospective analysis of the data of all children born in Tyrol between 1980 and 1999 and having an at least moderate permanent hearing loss in the better ear. RESULTS: The findings are that since UNHS was introduced in some newborn nurseries in 1995, a substantially higher number of hearing-impaired children has been detected early. For the whole sample, the increase of the early detection rate is 39.9%, with a 95% confidence interval of 33.2-46.8% (P<0.0001). For moderate hearing loss the increase is 49.2 with a 95% confidence intervall of 39.6-58.8% (P=0.000). CONCLUSIONS: On the whole, our findings lend support to the view that UNHS is effective in early detection of congenital hearing impairment. We conclude that UNHS provides the greatest benefit for moderately hearing-impaired children who, otherwise, would have been detected last.

Horner's syndrome after posterior spinal fusion in a child: a case report.

STUDY DESIGN: A case report of a complication after posterior spinal fusion. OBJECTIVES: To present the clinical findings of a Horner's syndrome after posterior spinal fusion. SUMMARY OF BACKGROUND DATA: A 14-year-old girl underwent posterior spinal fusion for idiopathic scoliosis. METHODS: Clinical examination and pharmacologic pupillary testing were used to diagnose Horner's syndrome. RESULTS: After surgery, the patient developed a left-sided Horner's syndrome. The Horner's syndrome had resolved 6 months after surgery except for slight ptosis. CONCLUSIONS: This is the first reported case of Horner's syndrome occurring after posterior spinal fusion without the use of epidural analgesia.

Analysis of radon-associated squamous cell carcinomas of the lung for a p53 gene hotspot mutation.

Squamous cell lung carcinomas (SCC) from former employees of the Wismut uranium mining company (Saxony, Germany) were obtained from the Stollberg Archive in order to screen for p53 tumour suppressor gene codon 249 arg-->met hotspot mutations, a putative molecular bio-dosimeter of alpha-particle (radon) exposure (Taylor et al (1994) Lancet 343: 86-87; McDonald et al (1995) Cancer Epidemiol Biomarkers Prevent 4: 791-793). Of the 29 archived samples of SCC meeting quality criteria for DNA analysis by polymerase chain reaction (PCR) and Haelll restriction enzyme digestion, two tumours were found that harboured this mutation. DNA sequencing confirmed the presence of a G to T base substitution within the Haelll site spanning codons 249 and 250 of the p53 gene that results in replacement of arginine (wild-type) by methionine at residue 249. When these data are combined with those from our previous study of tumours from the Stollberg Archive in which 50 lung tumours were examined, (including nine SCCs), we conclude that the G-->T (arg-->met) codon 249 mutation prevalence in the Wismut miner cohort is not sharply elevated in lung cancers in general (two mutations/79 tumours), or specifically in SCCs of the lung (two mutations/38 SCC) when compared to data from lung cancer patients with no reported occupational exposure to radon gas.