Plantarer ulzerierter Lichen ruber

Plantar ulcerations of lichen planus are unusual manifestations that constrain the patient’s quality of life and are often refractory to treatment. We report on a 71-year-old man in whom a prompt and complete healing of plantar ulcerative lichen planus was achieved by treatment with oral cyclosporine.     

Corticotropin-releasing factor in the dorsal raphe nucleus increases medial prefrontal cortical serotonin via type 2 receptors and median raphe nucleus activity

Interactions between central corticotropin-releasing factor (CRF) and serotonergic systems are believed to be important for mediating fear and anxiety behaviors. Recently we demonstrated that infusions of CRF into the rat dorsal raphe nucleus result in a delayed increase in serotonin release within the medial prefrontal cortex that coincided with a reduction in fear behavior. The current studies were designed to study the CRF receptor mechanisms and pathways involved in this serotonergic response. Infusions of CRF (0.5 μg/0.5 μL) were made into the dorsal raphe nucleus of urethane-anesthetized rats following either inactivation of the median raphe nucleus by muscimol (25 ng/0.25 μL) or antagonism of CRF receptor type 1 or CRF receptor type 2 in the dorsal raphe nucleus with antalarmin (25–50 ng/0.5 μL) or antisauvagine-30 (2 μg/0.5 μL), respectively. Medial prefrontal cortex serotonin levels were measured using in-vivo microdialysis and high-performance liquid chromatography with electrochemical detection. Increased medial prefrontal cortex serotonin release elicited by CRF infusion into the dorsal raphe nucleus was abolished by inactivation of the median raphe nucleus. Furthermore, antagonism of CRF receptor type 2 but not CRF receptor type 1 in the dorsal raphe nucleus abolished CRF-induced increases in medial prefrontal cortex serotonin. Follow-up studies involved electrical stimulation of the central nucleus of the amygdala, a source of CRF afferents to the dorsal raphe nucleus. Activation of the central nucleus increased medial prefrontal cortex serotonin release. This response was blocked by CRF receptor type 2 antagonism in the dorsal raphe. Overall, these results highlight complex CRF modulation of medial prefrontal cortex serotonergic activity at the level of the raphe nuclei.     

Sickle cell anemia patients have low erythropoietin levels for their degree of anemia

We have studied serum immunoreactive erythropoietin (SIE) levels in 28 patients with sickle cell anemia (SCA) without renal insufficiency and in 17 patients with nonhemoglobinopathy anemias of comparable severity using a sensitive radioimmunoassay procedure. An exponential relationship between SIE level and degree of anemia was noted in all patients. However, in nonhemoglobinopathy anemia, a sharp rise in the SIE level occurred as hemoglobin (Hb) levels fell below about 12 g/dL, whereas in sickle cell patients the increase was not marked until hemoglobin fell to about 9 g/dL. The response was more blunted in older SCA patients than in younger ones. A linear regression model relating SIE level to Hb level, presence/absence of SCA, and age explained 63% of the variation in SIE. We conclude that the serum erythropoietin levels in SCA increased at a lower hemoglobin concentration and are of a lower magnitude than that of the other anemias.     

Combining Automated Organoid Workflows with Artificial Intelligence-Based Analyses: Opportunities to Build a New Generation of Interdisciplinary High-Throughput Screens for Parkinson's Disease and Beyond

Parkinson's disease (PD) is the second most common neurodegenerative disease and primarily characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta of the midbrain. Despite decades of research and the development of various disease model systems, there is no curative treatment. This could be due to current model systems, including cell culture and animal models, not adequately recapitulating human PD etiology. More complex human disease models, including human midbrain organoids, are maturing technologies that increasingly enable the strategic incorporation of the missing components needed to model PD in vitro. The resulting organoid-based biological complexity provides new opportunities and challenges in data analysis of rich multimodal data sets. Emerging artificial intelligence (AI) capabilities can take advantage of large, broad data sets and even correlate results across disciplines. Current organoid technologies no longer lack the prerequisites for large-scale high-throughput screening (HTS) and can generate complex yet reproducible data suitable for AI-based data mining. We have recently developed a fully scalable and HTS-compatible workflow for the generation, maintenance, and analysis of three-dimensional (3D) microtissues mimicking key characteristics of the human midbrain (called “automated midbrain organoids,” AMOs). AMOs build a reproducible, scalable foundation for creating next-generation 3D models of human neural disease that can fuel mechanism-agnostic phenotypic drug discovery in human in vitro PD models and beyond. Here, we explore the opportunities and challenges resulting from the convergence of organoid HTS and AI-driven data analytics and outline potential future avenues toward the discovery of novel mechanisms and drugs in PD research. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society     

18F‐fluorodeoxyglucose positron emission tomography imaging in brain tumours: The Western Australia positron emission tomography/cyclotron service experience

¹⁸F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) scans in the first 49 patients referred with either possible brain tumour or brain tumour recurrence were reviewed. FDG‐PET imaging was reported with reference to anatomical imaging. Based on the report the FDG study was classified as either positive or negative for the presence of tumour. Thirty‐eight cases were included in the analysis, 21 having pathological data and 17 with diagnostic clinical follow up. Eleven were excluded, as they had inadequate follow‐up data. Of the 21 cases with pathology, 18 were shown to have tumour. In this group there were five false‐negative scans and two false‐positive PET scans. Seventeen cases were assessed by clinical follow up, nine were considered to have been tumour. There were two false negatives with one false positive. The overall sensitivity, specificity and positive and negative predictive values were 74, 73, 87 and 53% respectively. This is similar to figures previously quoted in published work. Despite relatively limited numbers, the utility of FDG PET imaging in our hands is similar to published reports. With a positive predictive value of 87%, a positive FDG study indicates a high likelihood that there is brain tumour present. A negative study does not exclude the presence of tumour.     

Minimal-invasive Therapie der Nierenbeckenabgangsenge

We report on 109 patients with ureteropelvic junction obstruction (UPJO) treated according to the following algorithm: intrinsic stenoses were treated by laser endopyelotomy (LEP). We used retroperitoneoscopy with ureterolysis to manage significant extrinsic UPJO due to a crossing vessel and either non-dismembered pyeloplasty in cases of an anterior vessel or dismembered pyeloplasty in cases of a posterior crossing vessel. Children were mostly treated by open dismembered pyeloplasty. Analysis of the factors that influence the postoperative results in the group of 64 patients treated by LEP showed significance for the presence of extrinsic causes of UPJO and the underlying grade of hydronephrosis. Based on our own results and the review of the literature, minimally invasive approaches for the management of UPJO have been proven safe and effective with results comparable to open surgery.     

Cost-effectiveness of cadaveric and living-donor liver transplantation

BACKGROUND: Cadaveric liver transplantation (5-year survival >80%) represents the standard of care for end-stage liver disease (ESLD). Because the demand for cadaveric organs exceeds their availability, living-donor liver transplantation has gained increasing acceptance. Our aim was to assess the marginal cost-effectiveness of cadaveric and living-donor orthotopic liver transplantation (OLT) in adults with ESLD. METHODS: Using a Markov model, outcomes and costs of ESLD treated (1) conservatively, (2) with cadaveric OLT alone, and (3) with cadaveric OLT or living-donor OLT were computed. The model was validated with published data. The case-based scenario consisted of data on all 15 ESLD patients currently on our waiting list (3 women, 12 men; median age, 48 years [range, 33-59 years]) and on the outcome of all OLT performed for ESLD at our institution since 1995 (n=51; actuarial 5-year survival 93%). Living-donor OLT was allowed in 15% during the first year of listing; fulminant hepatic failure and hepatocellular carcinoma were excluded. RESULTS: Cadaveric OLT gained on average 6.2 quality-adjusted life-years (QALYs) per patient compared with conservative treatment, living-donor OLT, an additional 1.3 QALYs compared with cadaveric OLT alone. Marginal cost-effectiveness of a program with cadaveric OLT alone and a program with cadaveric and living-donor OLT combined were similar (E 22,451 and E 23,530 per QALY gained). Results were sensitive to recipient age and postoperative survival rate. CONCLUSIONS: Offering living-donor OLT in addition to cadaveric OLT improves survival at costs comparable to accepted therapies in medicine. Cadaveric OLT and living-donor OLT are cost-effective.     

Living donor liver transplantation in patients with portal vein thrombosis: a survey and review of technical issues

BACKGROUND: Unlike cadaveric liver transplantation, current attitudes in living donor liver transplantation (LDLT) quote increased risk factors in the potential recipient such as retransplantation, multiple previous surgeries, or preexisting recipient portal vein thrombosis (PVT) as absolute or relative contraindications to this procedure. METHODS: An international survey was performed to examine the attitude of transplant teams relative to LDLT in the setting of preexisting PVT in the potential recipient. A questionnaire was sent to a total of 80 transplant centers performing LDLT in the United States, Europe, Canada, Japan, Southeast Asia, and Australia. RESULTS: A response was obtained from 47 transplant centers (59% response rate). This included 2146 LDLT procedures that combined both left and right lobe allografts. The incidence of acute preexisting recipient PVT was 18 (0.8%) and of chronic PVT was 26 (1.2%). Thrombectomy was performed in 28 (64%), a jump graft in 13 (29.5%), and a combination of both thrombectomy and a jump graft in 2 (4.5%) cases. With reference to the presence of preexisting PVT in the potential recipient, 5 centers considered this to be an absolute contraindication (10.7%), 24 centers as a relative contraindication (51%), and 18 as not being a contraindication (38.3%) to LDLT. CONCLUSIONS: The overall response to our questionnaire reflected a cautious attitude within the transplant community. Ethical criteria pertaining to risk undertaken by a healthy donor in situations of higher recipient morbidity risk does seem to impact on the decision to undertake LDLT in this group of patients.