The Histogenetic Base of Renal Capsular-derived Tumors

Capsulomas comprise a category of very rare benign tumors derived from the renal capsule, the most encountered being myxomas and leiomyomas. To get more information on the histogenetic origin of these tumors, a comprehensive ultrastructural investigation on the human renal capsule has been done on kidney biopsy samples performed for nephropathologic diagnosis. The human renal capsule ultrastructure is similar to that of the mammalian renal capsule. There are two cellular layers: an inner layer made up of particular (immature) smooth muscle cells, and a second outer layer consisting of fibroblasts, collagen fibers, extracellular matrix, and telocyte-like cells. Two cases of leiomyomas of microscopic dimensions, situated beneath the capsule have been described. Data from the literature presenting the ultrastructure and perirenal location of myxomas support the affiliation of these capsulomas with the resident renal capsular cells. Based on ultrastructural studies, the authors demonstrate the presence of telocyte-like cells in the outer layer of the human renal capsule and propose distinct histogeneses for leiomyomas and for capsular myxomas as derived from the inner and outer capsular layers, respectively.     

Stenotrophomonas maltophila cellulitis in an immunocompromised patient presenting with purpura,diagnosed on skin biopsy

Stenotrophomas maltophilia is an opportunistic Gram‐negative bacillus and an important cause of nosocomial infections, particularly in immunosuppressed individuals. Although infections with this organism are most often in the form of pneumonia, bacteremia and endocarditis, awareness of the impact of S. maltophilia skin infections has been increasing. Here we describe a case of S. maltophilia cellulitis in a 65‐year‐old man with severe neutropenia and purpuric skin lesions to highlight the critical histopathological findings and correlate them with the clinical manifestations of the skin infection with this organism. Because identification of S. maltophilia can be challenging and infections are difficult to manage, this case illustrates essential considerations regarding the multifaceted histopathological, dermatological, clinical and microbiological aspects of the diagnosis and treatment of S. maltophilia cellulitis in a severely immunocompromised patient. Cognizance of the increasing incidence of nosocomial infections with uncommon microorganisms such as S. maltophilia is necessary when presented with atypical cutaneous manifestations, particularly in immunocompromised patients.     

Somatic stem cells for regenerative dentistry

Complex human tissues harbour stem cells and/or precursor cells, which are responsible for tissue development or repair. Recently, dental tissues such as periodontal ligament (PDL), dental papilla or dental follicle have been identified as easily accessible sources of undifferentiated cells. The dental stem cell biology might provide meaningful insights into the development of dental tissues and cellular differentiation processes. Dental stem cells could also be feasible tools for dental tissue engineering. Constructing complex structures like a periodontium, which provides the functional connection between a tooth or an implant and the surrounding jaw, could effectively improve modern dentistry. Dental precursor cells are attractive for novel approaches to treat diseases like periodontitis, dental caries or to improve dental pulp healing and the regeneration of craniofacial bone and teeth. These cells are easily accessible and, in contrast to bone-marrow-derived mesenchymal stem cells, are more closely related to dental tissues. This review gives a short overview of stem cells of dental origin.     

Immunhistochemische Untersuchung des Kollagen-Typ-I-Gehalts der Gingiva bei Dysostosis cleidocranialis

Background

Patients with cleidocranial dysplasia (CCD) present a thickend and fibrotic gingiva.

Purpose

To the best of our knowledge it was analysed for the first time, whether this is correlated with an increased rate of collagen I in oral mucosa.

Patients and methods

27 soft tissue biopsies of six CCD-patients and 17 tissue samples of 12 healthy persons were labled with a monoclonal antibody against collagen I and the bound antibodies were detected with alkaline phosphatase-anti-alkaline phophatase-kit. The histological slices were analysed by a digital image recognition software under a fully automated microscope and the rate of collagen I was converted into amounts of grey tones.

Results

The amount of grey tones reached from 11.909 to 15.319 in the CCD-group, and from 2752 to 12.556 in the control group. The U-Test of Mann, Whitney and Wilcoxon for two independent samples generated a rank sum of 91,50 for CCD-patients, and of 79,50 for the control group. The Z-value was 3,246, the p-value 0,005. “Fisher`s exact test” identified a p-value of 0,0003.

Conclusions

The rate of collagen I in the oral mucosa seems to be increased significantly in CCD. This could explain the typical thick and fibrotic consistency of the gingiva and could be one reason for the delayed or missing dentition.     

Polymers Diffusivity Encoded by Stimuli‐Induced Phase Transition: Theory and Application to Poly(N‐Isopropylacrylamide) with Hydrophilic and Hydrophobic End Groups

The self‐diffusion of various nano‐objects investigated by high‐resolution nuclear magnetic resonance diffusometry proves to be an efficient method for the characterization of dynamics, aggregation kinetic, and matrix morphology. This study investigates how the two‐state model and Boltzmann function approach can be used for the evaluation of the thermodynamic parameters of temperature‐induced phase transition encoded in polymer diffusivity. The characteristics of the phase transition given by the transition temperature, change of entropy, and width of transition are obtained for poly(N‐isopropylacrylamide) (PNIPAm) linear polymers with hydrophilic and hydrophobic end‐group functionalization. The effect of end groups upon the polymer diffusivity is investigated as a function of molecular weight (M _n), from which fractal dimensions and hydrodynamic drag coefficients are obtained. The PNIPAm diffusivity is affected strongly by the end groups, and it is reflected in the hydrodynamic radius dependence upon molecular weight that obeys different power‐law relations. In this study, the synthesis of α‐ω‐heterotelechelic PNIPAm of different molecular weights with a thiol end group and a hydrophilic NIPAm‐like as well as a hydrophobic benzyl end group are described by reversible addition–fragmentation chain‐transfer polymerization.     

Recommendations from an International Consensus Conference on the Current Status and Future of Neoadjuvant Systemic Therapy in Primary Breast Cancer

The use of neoadjuvant systemic therapy (NST) for the treatment of primary breast cancer has constantly increased, especially in trials of new therapeutic regimens. In the 1980 s, NST was shown to substantially improve breast-conserving surgery rates and was first typically used for patients with inoperable locally advanced or inflammatory breast cancer. Investigators have since also used NST as an in vivo test for chemosensitivity by assessing pathologic complete response. Today, by using pathologic response and other biomarkers as intermediate end points, results from trials of new regimens and therapies that use NST are aimed to precede and anticipate the results from larger adjuvant trials. In 2003, a panel of representatives from various breast cancer clinical research groups was first convened in Biedenkopf to formulate recommendations on the use of NST. The obtained consensus was updated in two subsequent meetings in 2004 and 2006. The most recent conference on recommendations on the use of NST took place in 2010 and forms the basis of this report.     

Perampanel for focal epilepsy: insights from early clinical experience

Perampanel is approved for adjunctive therapy of focal epilepsy with or without secondarily generalized seizures in patients aged >12 years. This narrative review uses real‐world and clinical trial data to elucidate perampanel's role in the clinic. Audit data show good tolerability with perampanel and higher freedom‐from‐seizure rates in elderly vs younger patients. When using perampanel in elderly patients, special attention should be given to comorbidities and co‐medication to avoid potential interactions or adverse events. Slower titration is generally recommended, and seizure control should be reassessed at a dose of 4 mg before further dose increases. Perampanel efficacy is similar in adolescents and adults; however, somnolence, nasopharyngitis, and aggression are more frequent in adolescents vs the overall population. Individualized and slow‐dose titration can minimize adverse events. Low serum concentrations of perampanel may occur in patients also receiving some enzyme‐inducing anti‐epileptic drugs; a perampanel dose increase may be required. Adverse events of importance with perampanel include dizziness; anger, aggression, and hostile behavior (particularly in adolescents); and falls (particularly in patients >65 years). An individualized approach to dosing, including slower up‐titration and bedtime dosing, reduces dizziness risk. Other drugs may cause or aggravate dizziness; reducing concomitant drugs may be necessary when up‐titrating perampanel. It would seem clinically appropriate to give due consideration to avoiding use in patients with a history of anger or hostile/aggressive behavior. The possibility of such behaviors should be discussed with patients before starting perampanel, with monitoring during up‐titration. Slower up‐titration of perampanel in older patients helps reduce fall risk.     

High interindividual variability in the CD4/CD8 T cell ratio and natalizumab concentration levels in the cerebrospinal fluid of patients with multiple sclerosis

Strongly decreased leucocyte counts and a reduced CD4/CD8 T cell ratio in the cerebrospinal fluid (CSF) of natalizumab (NZB)‐treated multiple sclerosis (MS) patients may have implications on central nervous (CNS) immune surveillance. With regard to NZB‐associated progressive multi‐focal leucoencephalopathy, we aimed at delineating a relationship between free NZB, cell‐bound NZB, adhesion molecule (AM) expression and the treatment‐associated shift in the CSF T cell ratio. Peripheral blood (PB) and CSF T cells from 15 NZB‐treated MS patients, and CSF T cells from 10 patients with non‐inflammatory neurological diseases and five newly diagnosed MS patients were studied. Intercellular adhesion molecule‐1 (ICAM‐1), leucocyte function antigen‐1 (LFA‐1), very late activation antigen‐4 (VLA‐4), NZB saturation levels, and T cell ratios were analysed by flow cytometry. NZB concentrations were measured by enzyme‐linked immunosorbent assay (ELISA). Lower NZB saturation levels (P < 0·02) and a higher surface expression of ICAM‐1 and LFA‐1 (P < 0·001) were observed on CSF CD8 T cells. CSF T cell ratios (0·3–2·1) and NZB concentrations (0·01–0·42 µg/ml) showed a pronounced interindividual variance. A correlation between free NZB, cell‐bound NZB or AM expression levels and the CSF T cell ratio was not found. Extremely low NZB concentrations and a normalized CSF T cell ratio were observed in one case. The differential NZB saturation and AM expression of CSF CD8 T cells may contribute to their relative enrichment in the CSF. The reduced CSF T cell ratio appeared sensitive to steady‐state NZB levels, as normalization occurred quickly. The latter may be important concerning a fast reconstitution of CNS immune surveillance.     

Valproate in the treatment of epilepsy in girls and women of childbearing potential

This document provides guidance on the use of valproate in girls and women of childbearing age from a joint Task Force of the Commission on European Affairs of the International League Against Epilepsy (CEA‐ILAE) and the European Academy of Neurology (EAN), following strengthened warnings from the Coordination Group for Mutual Recognition and Decentralised Procedures‐Human (CMDh) of the European Medicines Agency (EMA), which highlight the risk of malformations and developmental problems in infants who are exposed to valproate in the womb. To produce these recommendations, the Task Force has considered teratogenic risks associated with use of valproate and treatment alternatives, the importance of seizure control and of patient and fetal risks with seizures, and the effectiveness of valproate and treatment alternatives in the treatment of different epilepsies. The Task Force's recommendations include the following: (1) Where possible, valproate should be avoided in women of childbearing potential. (2) The choice of treatment for girls and women of childbearing potential should be based on a shared decision between clinician and patient, and where appropriate, the patient's representatives. Discussions should include a careful risk–benefit assessment of reasonable treatment options for the patient's seizure or epilepsy type. (3) For seizure (or epilepsy) types where valproate is the most effective treatment, the risks and benefits of valproate and other treatment alternatives should be discussed. (4) Valproate should not be prescribed as a first‐line treatment for focal epilepsy. (5) Valproate may be offered as a first‐line treatment for epilepsy syndromes where it is the most effective treatment, including idiopathic (genetic) generalized syndromes associated with tonic–clonic seizures. (6) Valproate may be offered as a first‐line treatment in situations where pregnancy is highly unlikely (e.g., significant intellectual or physical disability). (7) Women and girls taking valproate require regular follow‐up for ongoing consideration of the most appropriate treatment regimen.