Genotype does not predict severity of behavioural phenotype in juvenile neuronal ceroid lipofuscinosis (Batten disease)

Aim The primary aim of this investigation was to examine genotype and clinical phenotype differences in individuals with juvenile neuronal ceroid lipofuscinosis (JNCL) who were homozygous for a common disease‐causing deletion or compound heterozygous. The secondary aim was to cross‐validate the Child Behavior Checklist (CBCL) and the Unified Batten Disease Rating Scale (UBDRS), a disease‐specific JNCL rating scale. Method Sixty individuals (28 males, 32 females; mean age 15y 1mo, SD 4y 9mo, range 5y 8mo–31y 1mo) with JNCL completed the UBDRS. Results No significant genotype and clinical phenotype differences were identified when comparing individuals homozygous for the deletion with a heterogeneous group of compound heterozygous individuals. There were significant correlations among related behaviour items and scales on the CBCL and UBDRS (Spearman’s rho ranging from 0.39 [p<0.05] to 0.72 [p<0.01]). Behaviour and physical function ratings were uncorrelated, supporting divergent validity of these two constructs in JNCL. Interpretation Previous reports of genotype and clinical phenotype differences were unsupported in this investigation, which did not find differences between individuals homozygous or heterozygous for the CLN3 deletion. The CBCL, an already validated measure of behaviour problems, appears valid for use in JNCL and cross‐validates well with the UBDRS.     

皮质类固醇激素局部应用的选择

局部应用皮质类固醇激素是治疗皮肤问题最古老、最有效的方法之一。临床上常用的皮质类固醇激素有很多,其药效和功能各有不同。应用皮质类固醇激素时,局部应用皮质类固醇激素是治疗皮肤问题最古老、最有效的方法之一。临床上常用的皮质类固醇激素有很多,其药效和功能各有不同。应用皮质类固醇激素时,     

Autonomic Modulation for the Treatment of Ventricular Arrhythmias: Therapeutic Use of Percutaneous Stellate Ganglion Blocks

Ventricular tachycardia (VT), ventricular fibrillation (VF), and electrical storm are commonly encountered emergency conditions in cardiac and surgical intensive care units. In most cases, recurrent ventricular arrhythmias or electrical storm are associated with a heightened sympathetic tone. These arrhythmias can be difficult to treat and may be refractory to beta‐blockade, antiarrhythmic therapy, sedation, and mechanical hemodynamic support. While monomorphic ventricular tachycardia and PVC‐triggered polymorphic ventricular tachycardia may sometimes be amenable to successful ablation, some patients may be too critically ill to make such an approach feasible. We present 2 cases of minimally invasive stellate ganglion blocks for the treatment of electrical storm in patients with advanced heart failure on mechanical life support. These cases are part of a collaborative initiative at our institution to use percutaneous stellate ganglion block as an adjunctive intervention to achieve control of life‐threatening ventricular arrhythmias.     

Early nephron formation in the developing mouse kidney

This paper reports 3-dimensional confocal microscopy observations on how nephrogenic aggregates form from the NCAM- and Pax2-positive caps (4–5 cells deep) of condensed metanephric mesenchyme surrounding the duct tips of the mouse kidney. Aggregates of 6–8 cells are first seen at ∼E12.5–12.75 immediately proximal to this cap, closely abutting the duct surface. As the tip advances, NCAM expression is maintained in the cap but is otherwise restricted to aggregates whose cells rapidly epithelialise, forming tubules that invade the duct epithelium. Pax2 expression studies shows how the rind of nephrogenic blastemal cells forms: as duct tips extend towards the kidney surface, the associated Pax2+ cells form patches of cells on the kidney surface. These observations revise our knowledge of the timing and process of nephron initiation.     

CLINICAL SIGNIFICANCE OF DENUDED UROTHELIUM IN BLADDER BIOPSY

PURPOSE: Although to our knowledge the significance of denuded urothelium in bladder biopsies has not been studied previously, it is thought to be a problem because benign urothelial cells are cohesive and not expected to shed into the urine. We correlated the pertinent clinical features of patients with denuded bladder biopsies and/or specific pathological features of denuded bladder biopsy specimens with patient outcome in regard to bladder lesions to help predict the subsequent likelihood of diagnosing bladder carcinoma in a patient with a nondiagnostic denuded biopsy. MATERIALS AND METHODS: We studied 51 denuded bladder biopsies from 44 patients in which the average extent of epithelial denudation was 90%. RESULTS: Of the 27 male (69%) and 17 female (31%) patients 22 to 86 years old (mean age 62) 34% had no history of bladder neoplasms. In remainder there were flat carcinoma in situ with or without other tumors (26%), high (20%) and low (14%) grade papillary tumors without carcinoma in situ and miscellaneous conditions (6%). Overall 31% of patients were diagnosed with carcinoma in situ within 24 months (median 5.5) after the denuded specimen was obtained. Parameters that did not correlate with the subsequent diagnosis of carcinoma in situ included cystoscopic impression, history of intravesical chemotherapy, sex, age, tissue inflammation, percent of tissue fragments with any denudation, number of denuded tissue fragments and percent of overall denuded epithelium. A history of carcinoma in situ before denuded biopsy predicted a diagnosis of carcinoma in situ within 24 months after denuded biopsy in 54% of patients in contrast to 19% of those without a history of carcinoma in situ (p = 0.03). Factoring in a history of other bladder tumor types in various combinations did not predict carcinoma in situ after denuded biopsy. The other predictive factor was cold cup biopsy. Carcinoma in situ developed within 24 months in 45% of patients in whom the denuded specimen was obtained by cold cup biopsy in contrast to none who underwent hot wire loop biopsy (p = 0.007). Cold cup biopsy and a history of carcinoma in situ were independently predictive. Carcinoma in situ developed within 24 months in 75% of patients with a history of that condition and a subsequent cold cup biopsy showing denuded epithelium. However, only 29% of those who underwent cold cup biopsy and had no history of carcinoma in situ were diagnosed with carcinoma in situ. CONCLUSIONS: In bladder biopsies obtained by a hot wire loop denudation most likely results from thermal injury when there is a low risk of subsequent carcinoma in situ. When the denuded biopsy sample was obtained by cold cup biopsy, particularly when associated with a history of carcinoma in situ, most cases represent neoplastic cell denudation and a high risk for subsequent carcinoma in situ.     

Pacemaker and Defibrillator Lead Entrapment: Case Studies

Cadavers and cineradiographic analysis have been used to document the effects of the medial subclavicular musculotendinous complex (MSMC) upon lead function. Four cadavers with pacemakers were dissected and photographed to demonstrate the course a lead takes as it passes through the costoclavicular region. One lead had been placed into the cephalic vein. In the other three cadavers, leads placed by currently accepted techniques of subclavian venipuncture were all found to pass through the soft tissues of the subclavicular region before entering the venous system. Cineradiographic results from a patient with a defibrillator, taken before and after replacement of a broken lead, show the effect of clavicular motion on a lead that passes through the MSMC. Furthermore, cineradiography makes it possible to identify the point where the lead entered the vein, and whether or not it escaped being caught up in the soft tissues of the MSMC.