[Posterior cortical atrophy. Pathology, diagnosis and treatment of a rare form of dementia]. / Posteriore kortikale Atrophie. Pathologie, Diagnostik und Behandlung einer seltenen Form der Demenz.

The syndrome of posterior cortical atrophy (PCA) is a rare clinical manifestation of several neurodegenerative diseases which affect the parieto-occipital cortex. The most frequent underlying pathology is Alzheimer's disease but some cases are caused by Lewy body disease, progressive subcortical gliosis, corticobasal degeneration or prion diseases. The most prominent clinical feature of PCA is complex visual disturbances including object agnosia, simultanagnosia, optical ataxia and oculomotor apraxia while basic visual functions remain intact. These deficits lead to multiple impairments in activities of daily living that require visual control. On progression of the disease amnestic, apraxic and dysexecutive symptoms occur so that a global dementia gradually emerges. At the core of the diagnostic work-up are a detailed patient history, accurate analysis of behavior and neuropsychological testing. Structural and functional brain imaging are suitable to demonstrate the localization of the disease process. Measurement of cerebrospinal fluid proteins (e.g. beta amyloid, tau, phospho-tau and 14-3-3) serves to confirm or exclude Alzheimer's disease or prion diseases. The mainstay of treatment are non-pharmacological interventions to support activities of daily living and personal independence. These treatments include cognitive training and compensatory strategies which can be prescribed as neuropsychological treatment or occupational therapy. If Alzheimer's disease or Lewy body disease is the likely cause, a treatment with cholinesterase inhibitor may be tried. Caregiver education and support are another essential part of the treatment regimen as with all forms of dementia.

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.

Low dose endoluminal photodynamic therapy improves murine T cell-mediated colitis.

BACKGROUND AND STUDY AIMS: Low dose photodynamic therapy (LDPDT) may modify the mucosal immune response and may thus provide a therapy for Crohn's disease. We evaluated the efficacy and safety of this technique in a murine T cell-mediated colitis model. METHODS: The safety of LDPDT was first tested in BALB/c mice. Naïve T cells were used to induce colitis in mice with severe combined immunodeficiency, which were followed up endoscopically, and a murine endoscopic index of colitis (MEIC) was developed. The efficacy of LDPDT (10 J/cm (2); delta-aminolevulinic acid, 15 mg/kg bodyweight) was then tested on mice with moderate colitis, while a disease control group received no treatment. The MEIC, weight, length, and histology of the colon, cytokine expression indices, number of mucosal CD4 (+) T cells, percentage of apoptotic CD4 (+) T cells, body weight, and systemic side effects were evaluated. RESULTS: LDPDT improved the MEIC ( P = 0.011) and the histological score ( P = 0.025), diminished the expression indices of the proinflammatory cytokines, interleukin-6 ( P = 0.042), interleukin-17 ( P = 0.029), and interferon-gamma ( P = 0.014), decreased the number of mucosal CD4 (+) T cells, and increased the percentage of apoptotic CD4 (+) T cells compared with the disease control group. No local or systemic side effects occurred. CONCLUSION: LDPDT improves murine T cell-mediated colitis, decreases the proinflammatory cytokines interleukin-6, interleukin-17, and interferon-gamma, and decreases the number of CD4 (+) T cells. No adverse events were observed. Therefore, this technique is now being evaluated in patients with inflammatory bowel disease.

Subpixel tracking for the analysis of outer hair cell movements.

CONCLUSION: Videomicroscopy with subpixel analysis is an excellent system for quantification of outer hair cell (OHC) movements. The resolution of a few nanometers is accurate enough to show induced differences of electromotility. OBJECTIVE: Electromotility of OHCs is a voltage-dependent process resulting from a membrane protein named prestin. Voltage sensitivity is conferred to prestin by intracellular anions. Reduction of these anions reduces electromotility. Videomicroscopy and subpixel tracking combine video-based analysis with a resolution of few nanometers. The aim of this study was to show the feasibility of a system for quantification of OHC movements. MATERIALS AND METHODS: Electromotility was investigated under normal and reduced intracellular chloride conditions. Cells were stimulated by the patch-clamp technique. Voltage steps were 500 ms long, ranging from -170 to +30 mV in 10 mV steps. RESULTS: As in previous studies our results show the following. The direction of OHC movement depends on the polarity of voltage steps, length changes are not equal for symmetrical voltage steps of opposite polarity, average shortening for a depolarizing step (-70 mV to +30 mV) is about 13 nm/mV. Hyperpolarization (-70 mV to -170 mV) on average evokes elongations of about 3 nm/mV. Half maximal chloride concentration reduces motility by 14%; half maximal electromotility is reached by a 94% reduction of chloride.

Maximizing the production of butyric acid from food waste as a precursor for ABE-fermentation.

The current study reports on the maximization of butyric acid production from food waste using a mixed microbial fermentation. In semi-continuous fermentations the effect of three different pH values (5.5, 7.0 and 9.0), three different temperatures (37°C, 55°C and 70°C) and two levels of hydraulic retention time (HRT, 2days and 6days) on the formation of butyric acid as well as total volatile fatty acid production (tVFA) were investigated. Overall, pH5.5 provided the lowest butyric acid concentrations regardless of the temperature and the HRT. At mesophilic temperature (37°C) alkaline conditions (pH9.0) lead to a strong incline of tVFA as well as butyric acid concentration probably due to a decreased solubilization of the substrate. However, most efficient in terms of butyric acid production was the fermentation conducted at 55°C and pH7 where a butyric acid concentrations of 10.55g/L (HRT 2days) and 13.00g/L (HRT 6days) were achieved. Additional experiments at 70°C showed declining butyric acid production. Increase of the HRT from 2days to 6days provided an increment of butyric acid concentration throughout almost all experimental settings. However, regarding volumetric productivity the increase in concentration does not compensate for the bigger reactor volume required to establish a higher HRT. At pH7 and 55°C the resulting volumetric production rates were 5.27g/L∗d at a HRT 2days and only 2.17g/L∗d at a HRT of 6days.

[Endoscopic diagnosis and therapy for gastrointestinal bleeding]. / Endoskopische Diagnostik und Therapie der gastrointestinalen Blutung.

Gastrointestinal bleeding is still one of the most frequent medical emergencies. Despite improvements in endoscopic diagnosis and therapy, mortality from bleeding is still high (15%). Since conclusive trials are lacking, the endoscopist often has to rely on personal experience in the selection of therapeutic options. Therefore this article gives an overview of new publications in this field and recommendations based on personal experience.

[Contribution of endoscopy in palliative oncology (endoprosthesis, photodynamic therapy, parenteral nutrition]. / Apport de l'endoscopie en oncologie palliative (endoprothèse, thérapie photodynamique, sonde de nutrition).

The aim of this review is to give an overview of palliative endoscopic treatment options in patients with advanced cancers of the esophagus, stomach, pancreas and bile ducts. With regard to esophageal cancers, we will also speak about curative endoscopic treatment (photodynamic therapy, mucosectomy) of early cancers and dysplasias. We will not approach to this subject in other types of carcinoma, since this has already been covered by the acquisitions of the last years.

De novo hemolytic uremic syndrome postrenal transplant after cytomegalovirus infection.

After renal transplantation, hemolytic uremic syndrome (HUS) may occur as recurrent disease or de novo. Here, we describe the de novo occurrence of HUS immediately after the onset of primary cytomegalovirus (CMV) disease in two renal allograft recipients. Patient no. 1 had primary CMV disease with biopsy-proven CMV esophagitis 2 months after transplantation. Patient no. 2 experienced primary CMV disease with fever and leukopenia 8 years after transplantation. Both patients were treated with intravenous ganciclovir. Both patients developed HUS with biopsy-proven thrombotic microangiopathy in the renal allograft only a few days (3 to 5 days) after the onset of CMV disease. The short interval between the onset of CMV disease and HUS, as well as the parallel course of CMV viremia and HUS in both patients, indicate there may be a pathophysiological link between both diseases. However, because antiviral therapy with ganciclovir was started before the onset of HUS in both patients, we cannot definitely rule out that HUS was triggered by ganciclovir.

The effect of 2450-MHz microwave radiation during microtubular polymerization in vitro.

Exposure to 2450-MHz (cw) microwave radiation causes inhibition of cell division in intact cells and varied in vivo biological effects in both avian and mammalian species. Because these reported effects may result from alterations in the dynamics of microtubule formation, we studied the effects of simultaneous microwave exposure (2450 MHz, cw) during each of the three critical stages of the intracellar polymerization cycle. In addition, using circular dichroism spectroscopy, we studied the effect of microwave irradiation on the secondary structure of purified tubulin polypeptides. These studies were accomplished using specially constructed exposure systems that permit the continuous recording of turbidometric or circular dichroism measurements during simultaneous exposure to microwaves. The baseline turbidity of microtubular protein did not change under the influence of microwave radiation (20 or 200 mW/g SAR) and irradiation had no effect on the light-scattering properties of the depolymerized protein. EGTA-induced polymerization and cold-induced depolymerization patterns were also similar for both control and microwave-irradiated samples. The circular dichroism spectrum of purified tubulin also did not appear to be influenced by microwave irradiation, indicating a lack of effect on the protein secondary structure. The data suggest that the cellular effects of microwaves are not due to changes in microtubular proteins or their rate of polymerization.

Photodynamic therapy of cholangiocarcinoma cancer.

Prognosis of nonresectable cholangiocarcinoma is not good, and in Bismuth type III and IV tumors relief of jaundice is seldom achieved, despite successful endoprosthesis insertion. Additional photodynamic therapy seems to be a promising new approach to these tumors. First pilot studies show relief of jaundice, mainly because of opening of the intrahepatic ducts and improvements in quality of life indices. Survival time seems to be long; however, randomized studies are necessary to confirm these results.

A novel method for the study of fluorescent probes in biological material during exposure to microwave radiation.

Instrumentation has been developed which allows the monitoring of fluorescence in erythrocyte ghost membranes before, during, and after exposure to microwave radiation. Using non-fluorescent, UV-transmitting fiber optic cables, excitation light of specific wavelengths was delivered to a stirred sample undergoing irradiation (2450 MHz, CW) within a fluid-filled, temperature-controlled waveguide. Fluorescence was collected using an identical cable and transferred through appropriate filters to standard detecting, amplification and recording devices. We have used the fluorescent probe, 1-anilino-8-naphthalene sulfonate (ANS) to monitor the effect of microwave radiation on the binding of calcium to erythrocyte ghosts. Microwave radiation at specific absorption rates of 10 and 200 mW/g had no effect on the binding of ANS to the membranes. Dose-response curves also showed no influence of microwaves on calcium binding between 2.0 and 10.0 x 10(-4) M. In addition, experiments studying fluorescence energy transfer between intrinsic tryptophan residues and membrane bound ANS showed that intermolecular distances between donor and acceptor are also unaffected by microwave radiation. We have thus shown that 2450 MHz microwave radiation at the specific absorption rates used does not interfere with the binding of calcium to erythrocyte ghosts or alter intermolecular distances between intrinsic molecules and bound ANS.

Counteracting ammonia inhibition in anaerobic digestion by removal with a hollow fiber membrane contactor.

The aim of the current study was to investigate the feasibility of membrane contactors for continuous ammonia (NH3-N) removal in an anaerobic digestion process and to counteract ammonia inhibition. Two laboratory anaerobic digesters were fed slaughterhouse wastes with ammonium (NH4⁺) concentrations ranging from 6 to 7.4 g/L. One reactor was used as reference reactor without any ammonia removal. In the second reactor, a hollow fiber membrane contactor module was used for continuous ammonia removal. The hollow fiber membranes were directly submerged into the digestate of the anaerobic reactor. Sulfuric acid was circulated in the lumen as an adsorbent solution. Using this set up, the NH4⁺-N concentration in the membrane reactor was significantly reduced. Moreover the extraction of ammonia lowered the pH by 0.2 units. In combination that led to a lowering of the free NH3-N concentration by about 70%. Ammonia inhibition in the reference reactor was observed when the concentration exceeded 6 g/L NH4⁺-N or 1-1.2 g/L NH3-N. In contrast, in the membrane reactor the volatile fatty acid concentration, an indicator for process stability, was much lower and a higher gas yield and better degradation was observed. The chosen approach offers an appealing technology to remove ammonia directly from media having high concentrations of solids and it can help to improve process efficiency in anaerobic digestion of ammonia rich substrates.

The pharmacokinetics and safety of porfimer after repeated administration 30-45 days apart to patients undergoing photodynamic therapy.

BACKGROUND: Porfimer is an intravenous (i.v.) injectable photosensitizing agent used in the photodynamic treatment of tumours and of high-grade dysplasia in Barrett's oesophagus. AIM: To assess the pharmacokinetics as well as the safety profiles of porfimer after a first and a second dose administered 30-45 days apart in patients undergoing photodynamic therapy. METHODS: Nineteen patients (16 with cholangiocarcinoma) were enrolled. Porfimer sodium was administered by i.v. injection over 3-5 min. Blood samples were collected prior to starting i.v. drug injection and postdose at different time points after the first and second administrations. RESULTS: Porfimer exposure values after the second administration were statistically higher than those observed after the first administration, suggesting a slight accumulation of porfimer following repeated administration. The apparent mean elimination half-life of porfimer increased from 410 h after the first administration to 725 h after the second administration. The safety profiles of porfimer after a first and a second administration were similar and did not raise additional concern. Eight patients experienced nine serious adverse events. Only photosensitivity was deemed study-drug related. CONCLUSION: Porfimer appears to display a safe and tolerable profile when used in patients requiring a second photodynamic therapy within 45 days.