Diagnostic value of vestibulo-ocular reflex parameters in the detection and characterization of labyrinthine lesions.

OBJECTIVE: To evaluate the power of various parameters of the vestibulo-ocular reflex (VOR) in detecting unilateral peripheral vestibular dysfunction and in characterizing certain inner ear pathologies. STUDY DESIGN: Prospective study of consecutive ambulatory patients presenting with acute onset of peripheral vertigo and spontaneous nystagmus. SETTING: Tertiary referral center. PATIENTS: Seventy-four patients (40 females, 34 males) and 22 normal subjects (11 females, 11 males) were included in the study. Patients were classified in three main diagnoses: vestibular neuritis: 40; viral labyrinthitis: 22; Meniere's disease: 12. METHODS: The VOR function was evaluated by standard caloric and impulse rotary tests (velocity step). A mathematical model of vestibular function was used to characterize the VOR response to rotational stimulation. The diagnostic value of the different VOR parameters was assessed by uni- and multivariable logistic regression. RESULTS: In univariable analysis, caloric asymmetry emerged as the most powerful VOR parameter in identifying unilateral vestibular deficit, with a boundary limit set at 20%. In multivariable analysis, the combination of caloric asymmetry and rotational time constant asymmetry significantly improved the discriminatory power over caloric alone (p<0.0001) and produced a detection score with a correct classification of 92.4%. In discriminating labyrinthine diseases, different combinations of the VOR parameters were obtained for each diagnosis (p<0.003) supporting that the VOR characteristics differ between the three inner ear disorders. However, the clinical usefulness of these characteristics in separating the pathologies was limited. CONCLUSION: We propose a powerful logistic model combining the indices of caloric and time constant asymmetries to detect a peripheral vestibular loss, with an accuracy of 92.4%. Based on vestibular data only, the discrimination between the different inner ear diseases is statistically possible, which supports different pathophysiologic changes in labyrinthine pathologies.

Development of bioreporter assays for the detection of bioavailability of long-chain alkanes based on the marine bacterium Alcanivorax borkumensis strain SK2.

Long-chain alkanes are a major component of crude oil and therefore potentially good indicators of hydrocarbon spills. Here we present a set of new bacterial bioreporters and assays that allow to detect long-chain alkanes. These reporters are based on the regulatory protein AlkS and the alkB1 promoter from Alcanivorax borkumensis SK2, a widespread alkane degrader in marine habitats. Escherichia coli cells with the reporter construct reacted strongly to octane in short-term (6 h) aqueous suspension assays but very slightly only to tetradecane, in line with what is expected from its low water solubility. In contrast, long-term assays (up to 5 days) with A. borkumensis bioreporters showed strong induction with tetradecane and crude oil. Gel-immobilized A. borkumensis reporter cells were used to demonstrate tetradecane and crude oil bioavailability at a distance from a source. Alcanivorax borkumensis bioreporters induced fivefold more rapid and more strongly when allowed physical contact with the oil phase in standing flask assays, suggesting a major contribution of adhered cells to the overall reporter signal. Using the flask assays we further demonstrated the effect of oleophilic nutrients and biosurfactants on oil availability and degradation by A. borkumensis. The fluorescence signal from flask assays could easily be captured with a normal digital camera, making such tests feasible to be carried out on, e.g. marine oil responder vessels in case of oil accidents.

Feasibility of in vivo 15N MRS detection of hyperpolarized 15N labeled choline in rats.

The increase of total choline in tumors has become an important biomarker in cancer diagnosis. Choline and choline metabolites can be measured in vivo and in vitro using multinuclear MRS. Recent in vivo(13)C MRS studies using labeled substrates enhanced via dynamic nuclear polarization demonstrated the tremendous potential of hyperpolarization for real-time metabolic studies. The present study demonstrates the feasibility of detecting hyperpolarized (15)N labeled choline in vivo in a rat head at 9.4 T. We furthermore report the in vitro (172 +/- 16 s) and in vivo (126 +/- 15 s) longitudinal relaxation times. We conclude that with appropriate infusion protocols it is feasible to detect hyperpolarized (15)N labeled choline in live animals.

Diabetische Neuropathien: Klinische Manifestationsformen, Früherkennung und Zuweisung zu einem Neurologen [Diabetic Neuropathies: Clinical sub-Types, Early Detection, and Asking Help from Neurologist].

In diabetes mellitus, it is expected to see a common, mainly sensitive, distal symmetrical polyneuropathy (DPN) involving a large proportion of diabetic patients according to known risk factors. Several other diabetic peripheral neuropathies are recognized, such as dysautonomia and multifocal neuropathies including lumbosacral radiculoplexus and oculomotor palsies. In this review, general aspects of DPN and other diabetic neuropathies are examined, and it is discussed why and how the general practionner has to perform a yearly examination. At the present time, some consensuses emerge to ask help from neurologist when faced to other forms of peripheral neuropathies than distal symmetrical DPN.

Diagnostic value of MRI for the detection of suspected placental invasion: Does it depend on observers' experience?

Purpose: To evaluate the diagnostic value of specific MR features for detection of suspected placental invasion according to observers' experience.Methods and Materials: Our study population included 25 pregnant women (mean age 35.16) investigated by prenatal MRI. In twelve out of them placental invasion was histopathologically proven, the 13 other women (52%) without placental invasion served as control group. Multiplanar T1- and T2-weighted sequences had been performed mostly without IV contrast injection (1.5 T). MR examinations of the two groups were rendered anonymous, mixed, then independently and retrospectively reviewed by two senior and two junior radiologists in view of 8 MR features indicating placentar invasion including the degree. Results were compared with surgical diagnosis (placenta normal/increta/accreta/percreta). Interobserver agrement between senior and junior readers were calculated. Stepwise logistic regression and receiver operating (ROC) curvers were performed.Results: Demographics between the two groups were not statistically different. Overall sensitivity and specificity for detecting placentar invasion was 90.9% and 75.0% for senior readers, and 81.8% and 61.8% for junior readers respectively. The most significant MR features indicating placentar invasion were T2 hypointense placental bands, followed by placenta praevia, focally interrupted myometrial border, posterior placental insertion, and heterogeneous placental signal. For each of the evaluated MR features the interobserver agreement kappa between the two senior readers was superior than that between the junior readers, ranging from bad (<0.4) to good (0.4-0.75).Conclusions: MRI can be a reliable and reproducible tool for detection of suspected placentar invasion, however very variable according to the observers' experience.

Performance of an automated multiplex immunofluorescence assay for detection of Chlamydia trachomatis immunoglobulin G.

Chlamydia serology is indicated to investigate etiology of miscarriage, infertility, pelvic inflammatory disease, and ectopic pregnancy. Here, we assessed the reliability of a new automated-multiplex immunofluorescence assay (InoDiag test) to detect specific anti-C. trachomatis immunoglobulin G. Considering immunofluorescence assay (IF) as gold standard, InoDiag tests exhibited similar sensitivities (65.5%) but better specificities (95.1%-98%) than enzyme-linked immunosorbent assays (ELISAs). InoDiag tests demonstrated similar or lower cross-reactivity rates when compared to ELISA or IF.

Bacterial contamination of platelet concentrates: pathogen detection and inactivation methods

Whereas the reduction of transfusion related viral transmission has been a priority during the last decade, bacterial infection transmitted by transfusion still remains associated to a high morbidity and mortality, and constitutes the most frequent infectious risk of transfusion. This problem especially concerns platelet concentrates because of their favorable bacterial growth conditions. This review gives an overview of platelet transfusion-related bacterial contamination as well as on the different strategies to reduce this problem by using either bacterial detection or inactivation methods.

Sensitive and rapid detection of ganciclovir resistance by PCR based MALDI-TOF analysis.

BACKGROUND: Cytomegalovirus (CMV) infection is associated with significant morbidity and mortality in transplant recipients. Resistance against ganciclovir is increasingly observed. According to current guidelines, direct drug resistance testing is not always performed due to high costs and work effort, even when resistance is suspected. OBJECTIVES: To develop a more sensitive, easy applicable and cost-effective assay as proof of concept for direct drug resistance testing in CMV surveillance of post-transplant patients. STUDY DESIGN: Five consecutive plasma samples from a heart transplant patient with a primary CMV infection were analyzed by quantitative real-time polymerase chain reaction (rtPCR) as a surrogate marker for therapy failure, and by direct drug resistance detection assays such as Sanger sequencing and the novel primer extension (PEX) reaction matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) based method. RESULTS: This report demonstrates that PEX reaction followed by MALDI-TOF analysis detects the A594V mutation, encoding ganciclovir resistance, ten days earlier compared to Sanger sequencing and more than 30 days prior to an increase in viral load. CONCLUSION: The greatly increased sensitivity and rapid turnaround-time combined with easy handling and moderate costs indicate that this procedure could make a major contribution to improve transplantation outcomes.

Contribution of ultrasonographic examination to the prenatal detection of trisomy 21: experience from 19 European registers.

The objective of this study was to evaluate the contribution of ultrasound scanning to the prenatal detection of trisomy 21 in a large unselected European population. Data from 19 congenital malformation registers in 11 European countries were included. The prenatal ultrasound screening programs in the countries ranged from no routine screening to three ultrasound investigations per patient. Routine serum screening was offered in four of the 11 countries and routine screening on the basis of maternal age amniocentesis in all. The results show that overall 53% of cases of trisomy 21 were detected prenatally with a range from 3% in Lithuania to 88% in Paris. Ninety-eight percent of women whose babies were diagnosed before 24 weeks gestation chose to terminate the pregnancy. Centres/countries that offer serum screening do not have a significantly higher detection rate of trisomy 21 when compared to those that offer maternal age amniocentesis and anomaly scanning only. Fifty percent of trisomy 21 cases were born to women aged 35 years or more. In conclusions, second trimester ultrasound plays an important role in the prenatal diagnosis of trisomy 21. Of those cases prenatally diagnosed, 64% of cases in women <35 years and 36% of those in women >or=35 years were detected because of an ultrasound finding. Ultrasound soft markers accounted for 84% of the scan diagnoses. There is evidence of increasing maternal age across Europe with 50% of cases of trisomy 21 born to women aged 35 years or more.

Development of a microfluidics biosensor for agarose-bead immobilized Escherichia coli bioreporter cells for arsenite detection in aqueous samples.

Contamination with arsenic is a recurring problem in both industrialized and developing countries. Drinking water supplies for large populations can have concentrations much higher than the permissible levels (for most European countries and the United States, 10 μg As per L; elsewhere, 50 μg As per L). Arsenic analysis requires high-end instruments, which are largely unavailable in developing countries. Bioassays based on genetically engineered bacteria have been proposed as suitable alternatives but such tests would profit from better standardization and direct incorporation into sensing devices. The goal of this work was to develop and test microfluidic devices in which bacterial bioreporters could be embedded, exposed and reporter signals detected, as a further step towards a complete miniaturized bacterial biosensor. The signal element in the biosensor is a nonpathogenic laboratory strain of Escherichia coli, which produces a variant of the green fluorescent protein after contact to arsenite and arsenate. E. coli bioreporter cells were encapsulated in agarose beads and incorporated into a microfluidic device where they were captured in 500 × 500 μm(2) cages and exposed to aqueous samples containing arsenic. Cell-beads frozen at -20 °C in the microfluidic chip retained inducibility for up to a month and arsenic samples with 10 or 50 μg L(-1) could be reproducibly discriminated from the blank. In the 0-50 μg L(-1) range and with an exposure time of 200 minutes, the rate of signal increase was linearly proportional to the arsenic concentration. The time needed to reliably and reproducibly detect a concentration of 50 μg L(-1) was 75-120 minutes, and 120-180 minutes for a concentration of 10 μg L(-1).

Use of radiolabelled monoclonal anti-CEA antibodies for the detection of human carcinomas by external photoscanning and tomoscintigraphy

Paul Ehrlich's inspired concept of 'magic bullets' for the cure of diseases has been revitalized by recent advances in immunology1. In particular, the development of cell fusion technology allowing the production of monoclonal antibodies (Mabs) with exquisite specificities2 triggered new hopes that we may now have the perfect carrier molecules with which to deliver cytotoxic drugs3 or toxins4 to the hidden cancer cells. This article reviews data on one aspect of the magic bullet concept, the use of radiolabelled antibodies as tracers for tumour localization. It will also discuss the very recent clinical use of 131I-labelled Mabs against carcinoembryonic antigen (CEA)5 to detect carcinoma either by conventional external photoscanning or by single photon emission computerized tomography (SPELT). This alliance of the most modern tools from immunology (Mabs) and nuclear medicine (SPELT) appears promising as a way to improve the sensitivity of 'immunoscintigraphy'. However, this approach is not yet ready, for widespread clinical use.

Detection of recurrence of large-bowel carcinoma by radioimmunoassay of circulating carcinoembryonic antigen (C.E.A.).

The usefulness and limitations of the carcinoembryonic antigen (C.E.A.) radioimmunoassay for the evaluation of tumour resection and for the detection of tumour relapse were studied in patients with large-bowel carcinoma. The level of plasma-C.E.A. was determined before any treatment in a group of 101 patients with histologically proven adenocarcinoma of the colon and rectum. 71% of all patients and 63% of cases with localised tumour (Dukes A and B) had a preoperative C.E.A. value of 5 ng. per ml. or higher. This limit was reached by only 1 of 90 apparently healthy, non-smoking blood-donors. Among 45 patients for whom a complete tumour resection was reported, all patients except 5 showed a drop of C.E.A. to normal values after surgery. The 5 patients whose C.E.A. did not fall to below 5 ng. per ml. showed a subsequent rise in C.E.A. level and were all found later to have a tumour relapse. The results indicate that an incomplete drop of circulating C.E.A. level one month after surgery has a bad prognostic significance. 22 of these patients were followed up by repeated C.E.A. radioimmunoassay for several months after surgery. 8 showed a progressive increase in C.E.A. levels preceding clinical diagnosis of tumour relapse by two to ten months. 6 other patients showed a moderate increase in C.E.A. levels, suggesting a tumour relapse not yet clinically detectable. The remaining 8 patients showed no increase in C.E.A. level above 5 ng. per ml. and no clinical symptoms of relapse. The results demonstrate that relapses of colon and rectum carcinoma can be detected by increased C.E.A. levels months before the appearance of any clinical evidence.

MR-IMPACT II: Magnetic Resonance Imaging for Myocardial Perfusion Assessment in Coronary artery disease Trial: perfusion-cardiac magnetic resonance vs. single-photon emission computed tomography for the detection of coronary artery disease: a comparative multicentre, multivendor trial.

Aims Perfusion-cardiac magnetic resonance (CMR) has emerged as a potential alternative to single-photon emission computed tomography (SPECT) to assess myocardial ischaemia non-invasively. The goal was to compare the diagnostic performance of perfusion-CMR and SPECT for the detection of coronary artery disease (CAD) using conventional X-ray coronary angiography (CXA) as the reference standard. Methods and results In this multivendor trial, 533 patients, eligible for CXA or SPECT, were enrolled in 33 centres (USA and Europe) with 515 patients receiving MR contrast medium. Single-photon emission computed tomography and CXA were performed within 4 weeks before or after CMR in all patients. The prevalence of CAD in the sample was 49%. Drop-out rates for CMR and SPECT were 5.6 and 3.7%, respectively (P = 0.21). The primary endpoint was non-inferiority of CMR vs. SPECT for both sensitivity and specificity for the detection of CAD. Readers were blinded vs. clinical data, CXA, and imaging results. As a secondary endpoint, the safety profile of the CMR examination was evaluated. For CMR and SPECT, the sensitivity scores were 0.67 and 0.59, respectively, with the lower confidence level for the difference of +0.02, indicating superiority of CMR over SPECT. The specificity scores for CMR and SPECT were 0.61 and 0.72, respectively (lower confidence level for the difference: -0.17), indicating inferiority of CMR vs. SPECT. No severe adverse events occurred in the 515 patients. Conclusion In this large multicentre, multivendor study, the sensitivity of perfusion-CMR to detect CAD was superior to SPECT, while its specificity was inferior to SPECT. Cardiac magnetic resonance is a safe alternative to SPECT to detect perfusion deficits in CAD.