Plasmapheresis in a Patient With "Refractory" Urticarial Vasculitis

Immune complexes are found in the circulation of 30%-75% of patients with urticarial vasculitis and much evidence supports the role of these immune complexes in the pathogenesis of urticarial vasculitis. Plasmapheresis is effective for removing these immune complexes; however, there are few reports on the use of plasmapheresis in the treatment of urticarial vasculitis. We describe a case of "refractory" urticarial vasculitis in which the symptoms improved after plasmapheresis treatment. We suggest that plasmapheresis be considered as an option in patients with severe or treatment-resistant urticarial vasculitis

Combinatorial use of bone morphogenetic protein 6, noggin and SOST significantly predicts cancer progression

Emerging evidence has indicated a role of the bone morphogenetic proteins (BMP) in the pathogenesis of certain cancers. The signaling of BMP family members is tightly regulated by their antagonists, including noggin and SOST, which are, in turn, positively regulated by BMP, thereby forming a negative feedback loop. Consequently, the expression of these antagonists should be taken into account in studies on the prognostic significance of BMP. In the present paper, we correlated protein and mRNA expression levels of BMP6, noggin and SOST, alone or in combination, with patient survival in various types of cancer. We found that BMP6 alone was not significantly correlated with esophageal squamous cell carcinoma patient survival. Instead, a high level of inhibitor of differentiation 1, a downstream factor of BMP6, was associated with shorter survival in patients whose tumors stained strongly for BMP6. Knockdown of noggin in esophageal cancer cell line EC109, which expresses BMP6 strongly and SOST weakly, enhanced the non-adherent growth of the cells. Noggin and SOST expression levels, when analyzed alone, were not significantly correlated with patient survival. However, high BMP6 activity, defined by strong BMP6 expression coupled with weak noggin or SOST expression, was significantly associated with shorter survival in esophageal squamous cell carcinoma patients. We further confirmed that BMP6 activity could be used as a prognostic indicator in prostate, bladder and colorectal cancers, using publicly available data on BMP6, noggin and SOST mRNA expression and patient survival. Our results strongly suggest that BMP6, noggin and SOST could be used in combination as a prognostic indicator in cancer progression. © 2012 Japanese Cancer Association.link_to_subscribed_fulltex

Digital holographic microscopy of the myelin figure structural dynamics and the effect of thermal gradient

Myelin figures (MFs) are cylindrical multilamellar lipid tubes that can be found in various healthy and diseased living cells. Their formation and dynamics involve some of the most mysterious configurations that lipid molecules can adopt under certain conditions. They have been studied with different microscopy methods. Due to the frequent coiling of their structure, the usual methods of microscopy fail to give precise quantitative information about their dynamics. In this paper, we introduced Digital Holographic Microscopy (DHM) as a useful method to calculate the precise dynamical volume, thickness, surface and length of the myelin figures. As an example of DHM imaging of myelin figures, their structure and growth rate in the presence and absence of temperature gradient have been studied in this work. We showed that the thickness of a myelin figure can be changed during the first few seconds. However, after approximately ten seconds, the thickness stabilizes and does not alter significantly. We further studied the effect of the thermal gradient on the length growth. The calculation of the length growth from the measurement of the myelin figure volume shows that the length (L) grows in time (t) as L is a proportionality of the square root of t at the early stage of the myelin protrusion in both the presence and the absence of the thermal gradient. However, thermal gradient facilitates the growth and increases its rate.Peer reviewedChemical Engineerin

Bone Morphogenetic Protein Signaling: Implications in Urology

The bone morphogenetic proteins (BMPs), as members of the transforming growth factor-β (TGF-β) superfamily, not only control bone formation, but also regulate multiple key steps during embryonic development and differentiation. Furthermore, BMPs play critical roles in maintaining the homeostasis of the cardiovascular, pulmonary, reproductive, urogenital, and nervous systems in adult life. Like all members of the TGF-β superfamily, BMP signaling is mediated through a heteromeric complex of type I and type II transmembrane serine/threonine kinase receptors. The subsequent signal transduction cascade includes either the canonical Smad-dependent or non-canonical Smad-independent pathways. Reflecting the critical function of BMPs, BMP signaling is tightly regulated at multiple steps by various mechanisms including extracellular endogenous antagonists, neutralizing antibodies/extracellular soluble receptor domains, small molecule inhibitors, cytoplasmic inhibitory Smads, and transcriptional co-repressors. Recently, dorsomorphin, the first small molecule inhibitor of BMP signaling, was identified and suggested as a useful tool for dissecting the mechanisms of signaling pathways and for developing novel therapeutics for diverse human diseases that are related to the BMP signaling pathways. In this article, we discuss various mechanisms involved in regulating BMP signaling pathways and their implications for urology

Race-free estimated glomerular filtration rate equation in kidney transplant recipients:development and validation study

OBJECTIVE: To compare the performance of a newly developed race-free kidney recipient specific glomerular filtration rate (GFR) equation with the three current main equations for measuring GFR in kidney transplant recipients.DESIGN: Development and validation study SETTING: 17 cohorts in Europe, the United States, and Australia (14 transplant centres, three clinical trials).PARTICIPANTS: 15 489 adults (3622 in development cohort (Necker, Saint Louis, and Toulouse hospitals, France), 11 867 in multiple external validation cohorts) who received kidney transplants between 1 January 2000 and 1 January 2021.MAIN OUTCOME MEASURE: The main outcome measure was GFR, measured according to local practice. Performance of the GFR equations was assessed using P 30 (proportion of estimated GFR (eGFR) within 30% of measured GFR (mGFR)) and correct classification (agreement between eGFR and mGFR according to GFR stages). The race-free equation, based on creatinine level, age, and sex, was developed using additive and multiplicative linear regressions, and its performance was compared with the three current main GFR equations: Modification of Diet in Renal Disease (MDRD) equation, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation, and race-free CKD-EPI 2021 equation. RESULTS: The study included 15 489 participants, with 50 464 mGFR and eGFR values. The mean GFR was 53.18 mL/min/1.73m 2 (SD 17.23) in the development cohort and 55.90 mL/min/1.73m 2 (19.69) in the external validation cohorts. Among the current GFR equations, the race-free CKD-EPI 2021 equation showed the lowest performance compared with the MDRD and CKD-EPI 2009 equations. When race was included in the kidney recipient specific GFR equation, performance did not increase. The race-free kidney recipient specific GFR equation showed significantly improved performance compared with the race-free CKD-EPI 2021 equation and performed well in the external validation cohorts (P 30 ranging from 73.0% to 91.3%). The race-free kidney recipient specific GFR equation performed well in several subpopulations of kidney transplant recipients stratified by race (P 30 73.0-91.3%), sex (72.7-91.4%), age (70.3-92.0%), body mass index (64.5-100%), donor type (58.5-92.9%), donor age (68.3-94.3%), treatment (78.5-85.2%), creatinine level (72.8-91.3%), GFR measurement method (73.0-91.3%), and timing of GFR measurement post-transplant (72.9-95.5%). An online application was developed that estimates GFR based on recipient's creatinine level, age, and sex (https://transplant-prediction-system.shinyapps.io/eGFR_equation_KTX/). CONCLUSION: A new race-free kidney recipient specific GFR equation was developed and validated using multiple, large, international cohorts of kidney transplant recipients. The equation showed high accuracy and outperformed the race-free CKD-EPI 2021 equation that was developed in individuals with native kidneys.TRIAL REGISTRATION: ClinicalTrials.gov NCT05229939.</p

Diverse molecular causes of unsolved autosomal dominant tubulointerstitial kidney diseases

Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD) is caused by mutations in one of at least five genes and leads to kidney failure usually in mid adulthood. Throughout the literature, variable numbers of families have been reported, where no mutation can be found and therefore termed ADTKD-not otherwise specified. Here, we aim to clarify the genetic cause of their diseases in our ADTKD registry. Sequencing for all known ADTKD genes was performed, followed by SNaPshot minisequencing for the dupC (an additional cytosine within a stretch of seven cytosines) mutation of MUC1. A virtual panel containing 560 genes reported in the context of kidney disease (nephrome) and exome sequencing were then analyzed sequentially. Variants were validated and tested for segregation. In 29 of the 45 registry families, mutations in known ADTKD genes were found, mostly in MUC1. Sixteen families could then be termed ADTKD-not otherwise specified, of which nine showed diagnostic variants in the nephrome (four in COL4A5, two in INF2 and one each in COL4A4, PAX2, SALL1 and PKD2). In the other seven families, exome sequencing analysis yielded potential disease associated variants in novel candidate genes for ADTKD; evaluated by database analyses and genome-wide association studies. For the great majority of our ADTKD registry we were able to reach a molecular genetic diagnosis. However, a small number of families are indeed affected by diseases classically described as a glomerular entity. Thus, incomplete clinical phenotyping and atypical clinical presentation may have led to the classification of ADTKD. The identified novel candidate genes by exome sequencing will require further functional validation

Varicella zoster infection in renal transplant recipients: prevalence, complications and outcome

Varicella zoster virus (VZV) is an important pathogen after renal transplantation. In the present study, we examined the prevalence, clinical presentation and outcome of VZV infections in renal transplant recipients. Charts and medical records of adult renal allotransplant recipients were investigated to find patients with VZV infection. From December 1972 until July 2010, 1,139 patients received kidney allograft at our institution. VZV infection was diagnosed in 40 patients (3.51%). 28 patients (70%) had intensified immunosuppression prior to VZV infection occurrence. Median time of onset was 2.13 years after transplantation (range 9 days to 19.2 years). 35 patients developed VZV during the first post-transplant year (median 0.61 years). Four patients developed VZV infection more than 12 years after transplantation. 33 patients (82.5%) had dermatomal distribution, 5 (12.5%) disseminated herpes zoster (HZ), and 2 patients (5%) who were VZV IgG-negative before transplantation, developed chickenpox. Immunosuppression was reduced and patients received acyclovir. Cutaneous scarring was recorded in 7 cases (17.5%). Two patients developed post-herpetic neuralgia, which was accompanied by scarring and skin depigmentation in 1 of them. Five patients (12.5%) experienced relapse of HZ. Timely initiation of therapy may prevent development of complications and the visceral form of disease. Based on our experience with development of chickenpox, we suggest active immunization for all seronegative patients before organ transplantation

Persistent hypoglossal artery

It is well known that the internal carotid artery has no branches in the neck during postfetal life (von Lanz & Wachsmuth, 1955), but during embryonic development there are anastomotic connections between the internal carotid and basilar artery that rarely persist after intrauterine life (Hassen-Khodja et al. 1992; Widmann & Sumpio, 1992; De Caro et al. 1995). The most common anomaly found incidentally on angiography is a persisting trigeminal artery, but persistent hypoglossal, otic and proatlantal arteries can also be found (Reynolds et al. 1980; Ouriel et al. 1988; Salas et al. 1998). We report a rare example of a persistent hypoglossal artery in a 64 y old female cadaver, cause of death unknown, embalmed by standard mortuary procedures for dissection during the routine anatomy course. The persistent hypoglossal artery originated from the anteromedial wall of the left internal carotid artery 2.5 cm above the bifurcation (Fig.). It extended towards the hypoglossal canal. The diameter of its lumen was 1.5 mm. During its course in the neck, it was positioned anterior to the internal carotid artery and medial to the facial and lingual arteries, the posterior belly of the digastric muscle and the convexity of the hypoglossal nerve in the neck. At 1 cm above the convexity of the hypoglossal nerve in the neck, the artery gave rise to a branch that entered the skull through the carotid canal anteromedial to the internal carotid artery (Fig. 1) and joined the basilar artery. The medial branch of the hypoglossal artery crossed the internal carotid artery on its medial side and entered the skull together with the hypoglossal nerve and joined the basilar artery. We found no other anomalies in the cerebral arterial system