Detection of virus-specific T cells via ELISpot corroborates early diagnosis in human Borna disease virus 1 (BoDV-1) encephalitis.

BACKGROUND: Within endemic regions in southern and eastern Germany, Borna disease virus 1 (BoDV-1) causes rare zoonotic spill-over infections in humans, leading to encephalitis with a high case-fatality risk. So far, intra-vitam diagnosis has mainly been based on RT-qPCR from cerebrospinal fluid (CSF) and serology, both being associated with diagnostic challenges. Whilst low RNA copy numbers in CSF limit the sensitivity of RT-qPCR from this material, seroconversion often occurs late during the course of the disease. CASE PRESENTATION: Here, we report the new case of a 40 - 50 year-old patient in whom the detection of virus-specific T cells via ELISpot corroborated the diagnosis of BoDV-1 infection. The patient showed a typical course of the disease with prodromal symptoms like fever and headaches 2.5 weeks prior to hospital admission, required mechanical ventilation from day three after hospitalisation and remained in deep coma until death ten days after admission. RESULTS: Infection was first detected by positive RT-qPCR from a CSF sample drawn four days after admission (viral load 890 copies/mL). A positive ELISpot result was obtained from peripheral blood collected on day seven, when virus-specific IgG antibodies were not detectable in serum, possibly due to previous immune adsorption for suspected autoimmune-mediated encephalitis. CONCLUSION: This case demonstrates that BoDV-1 ELISpot serves as additional diagnostic tool even in the first week after hospitalisation of patients with BoDV-1 encephalitis.

Compartment syndrome following thrombolysis: clinical features and associated conditions.

Major complications of thrombolysis are intracranial and extracranial bleedings. Compartment syndrome (CS) as a serious adverse event is sparsely reported. The purpose of the study is to present a systematic review of the literature on this complication based on a case vignette. A PubMed and Google Scholar search on CS following thrombolysis was performed. Twenty-four patients (11 male, 11 female, 2 not noted; median age 66 years, range 19-85 years) with thrombolysis associated CS were identified. Fifteen patients had thrombolysis with rtPA, 4 patients with streptokinase, 3 patients with urokinase, and 2 patients with tenecteplase. In 15 cases, CS affected the upper limb, and in 9 cases the lower limb. Indication for thrombolysis was myocardial infarction in 11 patients, arterial occlusion of the leg in 6 patients, pulmonary embolism in 4 patients, stroke in 2 patients, and deep venous thrombosis in 1 patient. In addition, in 15 cases, aspirin/ticlopidin, and/or heparin in therapeutic dosages had been prescribed. In 15 cases manipulations of the affected limb had been preceding. In both stroke patients, a hidden fracture was later diagnosed. The median time to the diagnosis of CS was 12 h (2 h-3 days). Therapy was mostly surgical with fasciotomy. The outcome of CS was favorable in 14 cases. However, in 5 cases, nerve damage persisted, and amputation was indicated in 2 patients. CS following thrombolysis is a rare condition. As predisposing factors different manipulations, hidden fracture and pronounced antithrombotic therapy are encountered.

Kidney-specific deletion of multidrug resistance-related protein 2 does not aggravate acute cyclosporine A nephrotoxicity in rats.

OBJECTIVE: Multidrug resistance-related protein 2 (Mrp2) is expressed in apical membranes of renal proximal tubular cells and contributes to the renal secretion of cyclosporine A (CsA). Mrp2⁻/⁻ deficiency may lead to local renal CsA accumulation. We investigated whether kidney-specific Mrp2 deficiency enhances acute CsA nephrotoxicity in rats. METHODS: Kidney-specific Mrp2 deletion was achieved by bilateral nephrectomy and transplantation of a congenic Mrp2-deficient kidney into wild-type recipients. Controls received a wild-type kidney. Animals were treated with CsA (10 or 30 mg/kg/day) for 7 days. Renal hemodynamics and renal cortical mRNA expression profile, oxidative stress, and the abundance of multidrug resistance protein 1 (Mdr1) and Mrp2 were assessed. RESULTS: CsA accumulation and CsA-induced reduction in glomerular filtration rate were similar in wild-type and Mrp2⁻/⁻ kidneys. Renal vascular resistance and agonist-induced renal vascular responses were similar in both groups. A PCR array on 84 genes involved in the biotransformation and antioxidant defense revealed increased CsA-induced mRNA expression of genes involved in oxidative and metabolic stress, inflammation, and apoptosis. This gene expression pattern was similar in wild-type and Mrp2⁻/⁻ kidneys. CsA increased the renal cortical oxidized glutathione, did not affect xanthine oxidase-dependent superoxide formation, and decreased renal cortical NADPH oxidase-dependent superoxide formation. Furthermore, CsA increased Mdr1 protein abundance to a greater extent in Mrp2⁻/⁻ than in wild-type kidneys. CONCLUSION: Mrp2 is not critical for renal CsA disposition and its deficiency does not enhance acute CsA nephrotoxicity. The high Mdr1 abundance may at least in part prevent exaggerated CsA accumulation in Mrp2⁻/⁻ kidneys.

Recurrent vertebrobasilar strokes and transient-ischemic attacks with challenging workup: Case report.

Detecting the stroke etiology in young patients can be challenging. Among others, determining causality between ischemic stroke and patent foramen ovale (PFO) remains a complicated task for stroke neurologists, given the relatively high prevalence of PFOs. Thorough diagnostic workup to identify incidental vascular risk factors and rare embolic sources is crucial to avoid premature PFO closure suggesting successful secondary stroke prevention. In this paper, we report on a 38-year-old patient with recurrent vertebrobasilar territory, especially right posterior inferior cerebellar artery (PICA) territory strokes. After the initial suspicion of a left vertebral artery (VA) dissection was not confirmed by ultrasound and magnetic resonance imaging (MRI) and other major risk factors were excluded, a PFO was detected and closed. Successful PFO closure was confirmed by transesophageal echocardiography, yet recurrent transient-ischemic attacks and vertebrobasilar strokes, especially during nighttime and in the early morning, occurred despite various antiplatelet and antithrombotic regimes and a persistent right-to-left shunt was detected by bubble transcranial Doppler. Finally, MRI after another vertebrobasilar infarction detected a transient left VA occlusion that finally led to the diagnosis of a left VA pseudoaneurysm from an incident emboligenic dissection in the atlas segment. This pseudoaneurysm together with an anatomical variant of the right PICA originating with the right anterior inferior cerebellar artery from the basilar artery finally explained the recurrent ischemic events of the patient. After successful treatment with coil occlusion, the patient suffered no further stroke and recovered completely. In summary, stroke in the young remains a diagnostic challenge. The incidental finding of a PFO should not deter from thorough stroke workup and the follow-up of these patients including PFO closure verification should be performed under the guidance of vascular neurologists.

The mycotoxin beauvericin impairs development, fertility and life span in the nematode Caenorhabditis elegans accompanied by increased germ cell apoptosis and lipofuscin accumulation.

Beauvericin is an ubiquitous mycotoxin with relevant occurrence in food and feed. It causes a high toxicity in several cell lines, but its general mechanism of action is not fully understood and only limited in vivo studies have been performed. We used Caenorhabditis elegans as a model organism to investigate effects of beauvericin. The mycotoxin displays a moderate acute toxicity at 100 µM; at this concentration also reproductive toxicity occurred (reduction of total progeny to 32.1 %), developmental toxicity was detectable at 250 µM. However, even lower concentrations were capable to reduce stress resistance and life span of the nematode: A significant reduction was detected at 10 µM beauvericin (decrease in mean survival time of 4.3 % and reduction in life span of 12.9 %). An increase in lipofuscin fluorescence was demonstrated starting at 10 µM suggesting oxidative stress as a mechanism of beauvericin toxicity. Beauvericin (100 µM) increases the number of apoptotic germ cells comparable to the positive control UV-C (400 J/m2). Conclusion: Low concentrations of beauvericin are capable to cause adverse effects in C. elegans, which may be relevant for hazard identification of this compound.

Evaluation of contrast-enhanced digital mammography.

PURPOSE: The goal of this prospective study was to evaluate the possible diagnostic benefits of contrast-enhanced digital mammography (CEDM) over conventional mammography. MATERIALS AND METHODS: Our analysis included data from 70 patients with a total of 80 lesions (30 malignant and 50 benign). A series of contrast-enhanced images was acquired from each patient using a modified imaging system (GE Senographe 2000D with copper filter) suitable for displaying iodine contrast medium. After the mask image had been taken, the contrast medium was administered using a dosage of 1ml/kg body weight at a rate of 4ml/s. Three contrast-enhanced images in the cranio-caudal projection plane were then captured at intervals of 60s. The mask image was logarithmically subtracted from the contrast-enhanced images. We performed a ROC analysis of diagnostic quality with three readers. RESULTS: On average, 5.66 more malignant lesions were detected with the addition of digital dynamic contrast mammography versus conventional mammography alone. The sensitivity was increased from an average of 0.43 in conventional mammography to an average of 0.62 with contrast mammography. Even in dense breast parenchyma, the sensitivity increased from an average of 0.35-0.59. In the multi-reader-ROC analyses of all readers, the differences in the AUC with p=0.02 (BI-RADS) proved statistically significant in all cases. The Wilcoxon test showed that Readers I and II primarily used the CEDM to upgrade enhancing lesions to a higher BI-RADS category or a higher probability of malignancy. These two readers benefited most from the CEDM in the ROC analysis. CONCLUSION: Overall, we conclude that the addition of dynamic digital subtraction mammography to conventional mammography can significantly improve diagnostic quality. The increased sensitivity is particularly pronounced in the case of dense breast tissue.