Elecsys Cerebrospinal Fluid Assays Accurately Distinguish Alzheimer's Disease from Frontotemporal Lobar Degeneration.

BACKGROUND: Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) are heterogeneous in their clinical presentation and underlying pathology, but they often have overlapping features. Diagnostic accuracy is critical for guiding patient management. Cerebrospinal fluid (CSF) diagnostic assays for the differentiation of AD and FTLD may increase diagnostic accuracy. OBJECTIVES: In this study, we aimed to understand the potential role of CSF biomarkers and biomarker ratios, measured using Elecsys® CSF immunoassays (Roche Diagnostics International Ltd, Rotkreuz, Switzerland), in the differential diagnosis of AD and FTLD. DESIGN: This study was conducted at a single center in Munich, Germany between July 2019 and July 2020. Patient CSF samples were retrospectively collected from the study center biobank. PARTICIPANTS: A total of 130 patients with cognitive impairment were included in the study; 86 patients were diagnosed with AD and 44 with FTLD (behavioral variant frontotemporal dementia, semantic variant of primary progressive aphasia, and non-fluent variant of primary progressive aphasia), based on core clinical criteria and a non-CSF biomarker, a typical pattern of regional hypometabolism on [18F] fluorodeoxyglucose positron emission tomography. MEASUREMENTS: Patient CSF biomarker concentrations were measured using Elecsys CSF immunoassays. Receiver operating characteristic analyses were conducted to determine areas under the curve (AUCs) for CSF biomarker performance. Sensitivity and specificity analyses were conducted to evaluate the performance of established cut-offs (Aß42 ≤1000 pg/mL, pTau181/Aß42 ratio >0.024, and tTau/Aß42 ratio >0.28) and optimized cut-offs based on Youden's index. RESULTS: AUC-based performance was similarly good for the pTau181/Aß42 ratio (AUC=0.841; 95% CI: 0.759-0.923), pTau181/Aß40 ratio (AUC=0.837; 95% CI: 0.754-0.919), Aß42/Aß40 ratio (AUC=0.829; 95% CI: 0.746-0.912), tTau/Aß42 ratio (AUC=0.822; 95% CI: 0.736-0.908), pTau181/Aß42/Aß40 ratio (AUC=0.817; 95% CI: 0.734-0.901), and Aß42 (AUC=0.812; 95% CI: 0.722-0.902). Performance was slightly lower for the tTau/Aß42/Aß40 ratio (AUC=0.799; 95% CI: 0.713-0.885), pTau181 alone (AUC=0.793; 95% CI: 0.707-0.880), tTau/Aß40 ratio (AUC=0.751; 95% CI: 0.657-0.844), and tTau alone (AUC=0.706; 95% CI: 0.613-0.799). The highest qualitative performance was observed with the pTau181/Aß42 ratio with an established cut-off value of >0.024 and optimized cut-off value of >0.022: sensitivity and specificity values were 0.892 and 0.773, respectively. CONCLUSIONS: Elecsys CSF immunoassays demonstrate good diagnostic accuracy in differentiating patients with AD from those with FTLD. These immunoassays have the potential to support clinical decision making, i.e. in diagnosing patients with FTLD by excluding patients with amyloid positivity, which is indicative of underlying AD.

Neck dissection: cause and effect.

OBJECTIVE: This study aimed to evaluate changes in neck dissection procedures over time in a tertiary university hospital to determine their influence on residency training. METHODS: Neck dissections performed in a recent decade (2003-2012) were retrospectively analysed and compared with those of an earlier decade (1981-1990). RESULTS: Nowadays, neck dissections are most frequently performed for thyroid (2003-2012 vs 1981-1990: 60.7 per cent vs 25 per cent, p = 0.002) and less often for epithelial malignancies (23.2 per cent vs 53.5 per cent, p = 0.002). Compared with dissections for thyroid spread, more dissections for epithelial malignancies are extensive (epithelial vs thyroid malignancies, 66 per cent vs 4.9 per cent) and more are performed after chemoradiation failures (25.6 per cent vs 0 per cent). CONCLUSION: This study demonstrates changes in neck dissection procedures over time. There is an increasing preference for conservative treatment for epithelial cancers. In addition, there is a large increase in both the diagnosis and surgical treatment of thyroid cancer. This shift may have a great effect on residents' learning curves and on their ability to achieve competency in performing neck dissections.

MN typing discrepancies based on GYPA-B-A hybrid.

BACKGROUND AND OBJECTIVES: Gene conversion events between GYPA and GYPB or GYPA and GYPE are facilitated by the close chromosomal proximity and high degree of sequence homology and can lead to the formation of GP hybrid genes. Discrepant results between blood group genotyping and haemagglutination in 22 random blood donors induced molecular characterization. MATERIALS AND METHODS: Sequence analysis of GYPA exons 1-7 and GYPB exons 1-5 was performed for gDNA and cDNA. The linkage of the nucleotide alterations was defined by haplotype separation. RESULTS: DNA analysis demonstrated a normal GYPA haplotype (GYPA*N n = 20, GYPA*M n = 2) with an altered GP hybrid nucleotide sequence in trans. A GYPB homologue sequence of minimal 10-bp encompassing intron 1 and exon 2 was translated into GYPA, accounting for an amino acid substitution from arginine to glutamic acid at position 13 (38 C>A). Genomic DNA analysis demonstrated the cis-linkage of the hybrid nucleotide sequence with each GYPA(Ser20, Gly24) (n = 20) associated with the expression of M and GYPA(Leu20, Glu24) (n = 2) encoding the N phenotype. The serologic data indicate that the changes do not affect the expression of a normal M and N antigen. cDNA sequences confirmed the gDNA results and furthermore identified a heterozygous deletion of GYPB exon 2 in all probands. CONCLUSION: The results document a GYPA-B-A hybrid gene, probably produced via a single unequal homologous recombination event. A segmental transfer of GYPB seems most likely accounting for the allelic dropout.

Improved performance characteristics of the von Willebrand factor ristocetin cofactor activity assay using a novel automated assay protocol.

UNLABELLED: BACKGROUND, OBJECTIVES AND METHODS: An accurate, sensitive and precise assay for reliable determination of the ristocetin cofactor activity of von Willebrand factor (VWF:RCo) in plasma and von Willebrand Factor (VWF)-containing concentrates has been evaluated. The assay is based on a commercially available automated protocol with modifications including a combination of adding additional ristocetin and the use of two calibration curves for the high and low measuring ranges. RESULTS: Addition of extra ristocetin resulted in improved measurement of VWF recoveries from various VWF-containing concentrates that were underestimated using the standard automated protocol. The modifications resulted in improved assay performance over an extended measuring range (2.00-0.03 IUmL(-1) ). Accuracy was tested using VWF deficiency plasma spiked with the 1st international standard (IS) for VWF concentrate. Seven dilutions, ranging from 1.80 to 0.05IUmL(-1) , were analyzed and resulted in measured concentrations between 80% and 100% of the assigned potency of the standard. Linearity was determined from the regression plot of the same concentrate dilutions and resulted in a correlation coefficient of 0.998. The repeatability, expressed as coefficient of variation, was 2% in the normal range (0.90IUmL(-1) ) and 8% at the level of 0.05IUmL(-1) . The corresponding reproducibility results were 2% and 15% at the normal and low measuring ranges, respectively. CONCLUSIONS: Analysis of patients with von Willebrand disease (VWD) indicates that the modified automated BCS(®) protocol has a superior discrimination power compared with the standard protocol. This is especially true in samples with low VWF, as in patients with type 3 VWD.

Anticomplementary activity of IVIG concentrates--important assay parameters and impact of IgG polymers.

BACKGROUND AND OBJECTIVES: A high concentration of large size polymers in intravenous immunoglobulin preparations was always correlated with high anticomplementary activity (ACA). In former days, high ACA was also linked to adverse reactions in patients. The goal of this study was to scrutinize critical parameters of the ACA assay and the influence of different polymer variants of IgG on the complement consumption. MATERIALS AND METHODS: Critical reagents as the complement and the preparation of erythrocytes were investigated. The influence of molecular integrity of IgG on the ACA was tested by subjecting IgG solutions ranging from pH 4.5 to 7.0 to heat treatment at 60 degrees C. RESULTS: The different complement batches had a significant impact on the test result of the ACA assay. It was demonstrated that polymers, provoked by heat treatment at pH values above 5.5, consumed complement almost completely whereas a polymer content up to 12% formed under acidic conditions did not lead to an increase in ACA. CONCLUSION: It was shown that suitable complement batches have to be identified in a screening procedure. Furthermore, it could be demonstrated that IgG polymers formed in the neutral pH range during heat treatment were potential ACA inducing compounds. Manufacturing the IVIG preparations under acidic conditions may help to avoid the formation of those ACA active polymers. Thus, intensive analysis of ACA during process development and validation is recommended.

Characterisation of a novel high-purity, double virus inactivated von Willebrand Factor and Factor VIII concentrate (Wilate).

This study summarises the biochemical and functional properties of a new generation plasma-derived, double virus inactivated von Willebrand Factor/Factor VIII (VWF/FVIII) concentrate, Wilate, targeted for the treatment of both von Willebrand disease (VWD) and haemophilia A. The manufacturing process comprises two chromatographic steps based on different performance principles, ensuring a high purity of the concentrate (mean specific activity in 15 consecutive production batches: 122 IU FVIII:C/mg total protein) and, thus, minimising the administered protein load to the patient (specification: < or = 15 mg total protein per 900 IU Wilate). The optimised solvent/detergent (S/D) treatment and prolonged terminal dry-heat (PermaHeat) treatment of the lyophilised product at a specified residual moisture (RM) provide two mechanistically independent, effective and robust virus inactivation procedures for enveloped viruses and one step for non-enveloped viruses. These process steps are aggressive enough to inactivate viruses efficiently, but yet gentle enough to maintain the structural integrity and function of the VWF and FVIII molecules, as proven by state-of-the-art assays covering the diverse features of importance. The VWF multimeric pattern is close to the one displayed by normal plasma, with a consistent content of more than 10 multimers, but a relatively lower portion of the very high multimers. The multimeric triplet structure is normal, underlining the gentle and effective manufacturing process, which does not require the addition of protein stabilisers at any step. The balanced activity ratio of VWF to FVIII is close to that of plasma from healthy subjects, rendering Wilate suitable also for the safe and effective treatment of patients with VWD.

[The time-course of action of rapacuronium and mivacurium after early reversal following equally lasting relaxation]. / Spontane und induzierte neuromuskuläre Erholung nach gleich langer Relaxierung mit Rapacuronium und Mivacurium.

This study was designed to compare the time course of action and the safety profile of Rapacuronium and Mivacurium in day case dental surgery. After Ethics Committee approval 61 healthy adult patients, scheduled for dental day case surgery, were randomised in an assessor-blinded manner to receive either 1.5 mg/kg Rapacuronium with and without 0.05 neostigmine 5 min later (19 patients each) or a total of 0.25 mg/kg Mivacurium (n = 16). Anaesthesia was induced using Propofol 2 - 5.1 mg/kg and Remifentanil 24 - 73 mcg/kg/h and maintained with Desflurane in N2O/O2 (2/1). Endotracheal intubation was performed when maximum blockade was achieved and scored by a blinded intubator. Neuromuscular block was monitored using the train-of-four response to supramaximal stimuli at the ulnar nerve every 15 seconds using acceleromyography (TOF Watch SX). Onset time, clinical duration (reappearance of the third twitch of a TOF-stimulation) and recovery to T4/T1 > 0.9 were recorded. Speed of recovery was evaluated by the time difference between reappearance of the third twitch and T4/T1 > 0.9. The intubating conditions at the time of maximum block revealed no statistically significant differences between the three groups. Changes in blood pressure, heart rate and airway pressure were not significant. Onset time in subjects who received Rapacuronium (99 +/- 29 s) was faster compared to the onset time in those who received Mivacurium (157 +/- 36 s). Also clinical duration was significantly shorter following Rapacuronium without reversal (12 +/- 4 min) as well as with reversal (9 +/- 1 min) compared with Mivacurium (21 +/- 5 min)). Patients treated with Rapacuronium and reversal recovered faster (14 +/- 8 min)) compared to the other two groups (Mivacurium: 20 +/- 6 min, Rapacuronium without reversal: 31 +/- 9 min). The fraction of clinical duration of the total duration was highest following Mivacurium (51 %) when compared with Rapacuronium/Neostigmine (43 %) and Rapacuronium (28 %).

3D dosimetry study of 188Re liquid balloon for intravascular brachytherapy using bang polymer gel dosemeters.

It has been suggested that the combination of intravascular brachytherapy and coronary stent implantation may result in further reduction of restenosis after percutaneous balloon angioplasty. The use of an angioplasty balloon filled with a 188Re liquid beta source for intravascular brachytherapy provides the advantages of accurate source positioning and uniform dose distribution to the coronary vessel wall. The effect of source edge and stent on the dose distribution of the target tissue may be clinically important. In BANG gels, the absorbed radiation produces free-radical chain polymerisation of acrylic monomers that are initially dissolved in the gel. The number of polymer particles is proportional to the absorbed dose. In this study, 3D dose distributions are presented for 188Re balloons, with and without stents, using a prototype He-Ne laser CT scanner and the proprietary BANG polymer gel dosemeters.

[Motor function during patient-controlled analgesia via a lumbar epidural catheter after major abdominal surgery. Ropivacaine-sufentanil vs. bupivacaine-sufentanil]. / Motorische Blockade während einer patientenkontrollierten lumbalen Epiduralanalgesie nach abdominellen Eingriffen - Ein Vergleich zwischen Ropivacain-Sufentanil und Bupivacain-Sufentanil.

INTRODUCTION: The aim of the present study was to investigate postoperative motoric impairment during patient-controlled analgesia after major abdominal surgery with ropivacaine-sufentanil and bupivacaine-sufentanil via a lumbar epidural catheter. METHODS: After approval of the local ethics committee, 40 patients scheduled for major lower abdominal surgery were randomly allocated to receive bupivacaine 0.25 % or ropivacaine 0.2 %, both with sufentanil 2 microgram/ml in a double blind manner. General anaesthesia (midazolam, etomidate, fentanyl, vecuronium, and desflurane in N2O/O2) and postoperative management of the patients were standardised. Postoperatively, the motoric function and ability for active early mobilisation was examined clinically (application of the Bromage scale, ability to leave the bed and ability to walk). Reduction of muscular force of the legs was measured postoperatively using a scale and compared with preoperative baseline values. To ensure a similar level of analgesia, a 10-cm visual analogue scale was applied at rest and while coughing. RESULTS: The two groups did not differ with respect to the demographic data and postoperative levels of analgesia. Less reduction of motoric function at rest was observed in the ropivacaine group (p = 0,044). However, this did not lead to an increased ability to get up from bed (p = 0,57) or to walk around (p = 0,17). A high number of patients did not meet the requirements for early ambulation. Almost half of the patients of both groups were unable to leave their beds in the morning of the first postoperative day. On the second postoperative day about 25 - 30 % of the patients could not walk even when support was applied. Furthermore, median reduction (10th/90th percentile) of muscular strength was reduced to 50 % (37 %/76 %) in the ropivacaine group and to 48 % (31 %/61 %) in the bupivacaine group compared with preoperative values. DISCUSSION: While quality of analgesia was similar, mobility of the legs at rest is better preserved with ropivacaine 0.2 % than with bupivacaine 0.25 %. However, despite the fact that high dose sufentanil was added to both local anaesthetics, there was marked motoric impairment in both groups probably due to the lumbar site of the epidural catheter. This was associated with an unacceptable high incidence of patients unsuitable for early postoperative mobilisation.

Encapsulation of isotope on novel beta-emitting poly(ethylene terephthalate) surfaces.

Recent data indicate that intravascular betaa-irradiation from centrally located sources at the time of balloon angioplasty or stenting reduces proliferation of smooth muscle cells, neointima formation, and restenosis. In an effort to simplify radiation delivery, a novel beta-radiation source was developed based on the adsorption of 32P (phosphoric acid) by pH-sensitive chitosan hydrogel on a poly(ethylene terephthalate) balloon surface. To prevent the 32P-isotope desorption in the patient's blood, the adsorbed phosphoric acid was precipitated as CaHPO4 on the surface by a saturated Ca(OH)2/5% CaCl2 solution. Various polyurethanes were applied to seal the radioactive surface by the dip-coating method. The isotope off-rate results were determined. Optimal results were obtained by serially coating with two polyurethane solutions. This approach holds promise for simplifying and improving the safety, and minimizing the cost of intravascular brachytherapy.

Vocal cord paralysis secondary to impacted esophageal foreign bodies in young children.

Impacted foreign bodies in the esophagus can result in respiratory symptoms including stridor and aphonia. Several mechanisms have been proposed to explain these symptoms, but the possibility of vocal cord paralysis and its cause has not been adequately emphasized. Two cases of young children with esophageal foreign body are described; both presented with respiratory symptoms, 1 with aphonia and the other with stridor. In both cases, the symptoms were secondary to vocal cord paralysis. A possible mechanism of recurrent nerve injury is proposed.

Vertebral artery dissection in Turner's syndrome: diagnosis by magnetic resonance imaging.

Aortic artery dissection is a rare but well-recognized complication of Turner's syndrome. Isolated carotid or vertebral artery dissection has not previously been reported. The authors report the clinical and magnetic resonance imaging findings in a 30-year-old woman with Turner's syndrome who developed a high cervical spinal cord infarction with a Brown-Sequard syndrome owing to bilateral vertebral artery dissection. The diagnosis and management of the case is reviewed.

Novel beta-emitting poly(ethylene terephthalate) surface modification.

Restenosis after percutaneous interventions in coronary and peripheral arteries leads to repeat procedures and surgery in a significant number of patients. We have previously demonstrated that irradiation of an arterial site using an endovascular source (brachytherapy) is highly effective in preventing the restenotic process. To this end, a novel beta radiation delivery system was developed, based on the adsorption of (32)P (o-phosphoric acid) by pH-sensitive chitosan hydrogel on a poly(ethylene terephthalate) (PET) balloon surface. The PET balloon surface was treated with oxygen plasma and coated with chitosan hydrogel. Covalent bonds, ionic bonds, and hydrogen bonds all contribute to the adhesion between chitosan hydrogel and PET. In the aqueous phosphoric acid (PA) solution, the -NH(2) groups of chitosan were protonated by PA and the adsorption of PA occurred at the same time. The effect of PA concentration and temperature on adsorption efficiency and kinetics were studied. More than 70% PA was adsorbed on the sample surface in 0.2 mM PA solution. The surface of samples was also investigated by attenuated total reflection-Fourier transform infrared spectroscopy and scanning electron microscopy. PET surface may be modified to carry high activity beta emitters; such materials may be useful in a therapeutic setting

Natural history of aortic arch atherosclerotic plaque.

To define the natural history of aortic arch plaque, we used B-mode ultrasonography to perform sequential study of the aortic arch. Eighty-nine patients were studied for up to 18 months. There was no change in 67% of total plaques; 77% of simple plaque (<4 mm) and 48% of complex plaque (> or =4 mm) did not progress. Atherosclerosis of the aortic arch can be sequentially studied with B-mode ultrasonography, and most of these lesions remain unchanged after up to 18 months of observation.

Plaque morphology correlates with cerebrovascular symptoms in patients with complex aortic arch plaque.

BACKGROUND: Studies of aortic arch plaques with transesophageal echocardiography have demonstrated that complex aortic arch plaques (CAPs) greater than or equal to 4 mm in thickness are associated with ischemic stroke. Recent studies have demonstrated that the morphological features of plaques may aid in the identification of aortic plaques that are more likely to be associated with embolic stroke. OBJECTIVE: To identify aortic plaques that are more likely to be associated with embolic stroke by means of their morphological features. METHODS: Transcutaneous B-mode ultrasonography was used to image aortic arch plaques in 500 consecutive patients. The criteria used to identify the morphological features of carotid artery plaques that are more likely to be associated with ischemic stroke (heterogeneous rather than homogeneous) were applied to aortic arch plaques. Statistical comparisons were made using the Fisher exact test. RESULTS: Ischemic symptoms (eg, stroke, transient ischemic attack, and amaurosis fugax) were present in 38% of 104 patients with CAP and in 34% of 391 patients without CAP. Nineteen (51%) of 37 patients with heterogeneous CAP were symptomatic. Twenty-one (31%) of 67 patients with homogeneous CAP were symptomatic (P = .04). CONCLUSION: Transcutaneous B-mode ultrasonography of the aortic arch can help to identify heterogeneous plaques that are more likely to be associated with ischemic stroke using morphological criteria derived from studies of carotid artery plaque.

William James and the unconscious: redressing a century-old misunderstanding.

Contrary to received wisdom in psychology, William James did not oppose postulating unconscious processes. This mistaken belief stems from a misreading of a passage in his Principles concerned with disproving the metaphysical notion that mental states are composed of elementary mental units. The term unconscious had been co-opted by individuals who supported this position. Unconscious did not mean then what it means now. Analysis of the rest of the Principles, his later works, and his reactions to the works of others reveals that James actually supported what we would now term unconscious processes. He even contributed to their study with his notions of the "fringe," "habit," and "subconscious incubation." Causes and effects of this misunderstanding are discussed.

Antiphosphatidyl serine antibodies are independently associated with ischemic stroke.

OBJECTIVE: To determine whether elevated titers of antiphosphatidyl serine antibodies (aPS) are associated with an increased risk of ischemic stroke in a general stroke population. BACKGROUND: aPS are members of the family of antiphospholipid antibodies that has been associated with increased stroke risk. Although aPS have been demonstrated to occur in 18% of a group of young patients with cerebrovascular symptoms, their prevalence in the general stroke population is unknown, and no controlled study to assess the strength of their association with ischemic stroke has been undertaken previously. METHODS: A case-control study comparing 267 acute ischemic stroke patients and 653 community controls. Sera were obtained immediately after acute stroke in patients. Titers of IgG aPS >16 IgG phospholipid units or IgM aPS >22 IgM phospholipid units were considered positive. Odds ratios (ORs) were obtained by logistic regression, adjusting for age, gender, race/ethnicity, history of hypertension, diabetes mellitus, cardiovascular disease, and cigarette smoking. RESULTS: The adjusted OR was 5.6 (95% confidence interval [CI] 1.8, 18.0) for IgG aPS and 2.9 (95% CI 1.6, 5.3) for IgM aPS. The adjusted OR for either an elevated IgG or IgM aPS was 3.2 (95% CI 1.8, 5.5). CONCLUSIONS: This study demonstrates that elevated IgG and IgM antiphosphatidyl serine antibodies titers are associated with increased risk of ischemic stroke. The prevalence of these antibodies is lower, but the associated stroke risk is comparable with that of anticardiolipin antibodies.