Oral Everolimus for Treatment of a Giant Left Ventricular Rhabdomyoma in a Neonate—Rapid Tumor Regression Documented by Real Time 3D Echocardiography

The presented case reports on successful treatment with everolimus in a neonate with left ventricular giant rhabdomyoma. The authors used a different dosage regime compared to literature and documented rapid tumor regression by 3D echocardiography.     

Isolation of DNA from the centromere of human chromosome 7 by microdissection

Centromeres remain the least characterized regions of human chromosomes because they have a very high content of repetitive DNA. Here, we describe a micro-dissection library from the centromeric region of human chromosome 7 and its use for generating sequence tagged sites (STSs). The library contains about 1500 clones with an average insert size of 150 bp and only about 15% of the clones harbour repetitive human DNA. Seven clones hybridizing to alphoid DNA were found to correspond to a fragment of the D7Z2 alphoid array on chromosome 7, thus confirming the origin of the library. A number of clones not containing known repetitive DNA were used to generate STSs that identified yeast artificial chromosomes (YACs) and in turn allowed the STSs to be placed on the physical map. One STS is located between the two Genethon genetic markers closest to the centromere on the q side. Another STS was located 3–4 cM away in 7q11.2, while a third identified YACs containing both low-copy and alphoid sequences that are not yet mapped but are clearly centromeric. The library therefore comprises a collection of sequences from the centromeric region of chromosome 7 that can be used to generate STSs and to map the entire centromeric region.This revised version was published online in November 2005 with corrections to the Cover Date.     

Active detachment involves inhibition of cell-matrix contacts of malignant melanoma cells by secretion of melanoma inhibitory activity

Melanoma inhibitory activity (MIA) has been identified as a small protein secreted from malignant melanoma cells. Recent results revealed a direct interaction of MIA and epitopes within extracellular matrix proteins including fibronectin. The aim of this study was to analyze functional consequences mediated by this interaction. Here we show that MIA interferes specifically with attachment of melanoma cells to fibronectin, a phenomenon we refer to as active detachment. Antibodies inhibiting binding of alpha4beta1 and alpha5beta1 integrins to fibronectin cross-react specifically with MIA, suggesting that MIA shares significant structural homology with the binding pockets of these integrins and thereby masks the respective epitopes on extracellular matrix molecules. Several peptides derived from fibronectin and from a phage display screening were tested with respect to a potential MIA-inhibitory effect. In vitro tests identified two peptides affecting MIA function; both inhibited growth of melanoma metastases in vivo. In summary, we conclude that MIA may play a role in tumor progression and spread of malignant melanomas via mediating active detachment of cells from extracellular matrix molecules within their local milieu. Further, our results suggest that inhibiting MIA functions in vivo may provide a novel therapeutic strategy for metastatic melanoma disease.     

Early detection of metastasis by alterations in the cellular immune system in the murine liver and blood

We investigated the reaction of the cellular immune system of liver and blood in the C57BL/6 mouse to a metastasizing Lewis lung carcinoma. The cellular immune system of the liver consists of mature and immature macrophages, B-cells, T-cells including their subpopulations, and natural killer cells, and their percentage frequencies differ significantly from those in the corresponding mononuclear blood cell (MBC) compartment. This suggests that the hepatic immune cells represent a system with autonomous function showing a typical homing of its members. Imminent metastasis to the liver is signalled by impressive alterations in the percentage frequencies of nonparenchymal liver cells (NPLC). There are a dramatic loss of mature macrophages, an increase in immature macrophages, a reduction of T-helper cells leading to a low CD4/CD8 ratio, and an increase in natural killer cells. In the blood, the corresponding precursor cells show comparable changes with a delay of at least 2 days. Early metastasis is accompanied by a significant increase in mononuclear NPLC producing tumour necrosis factor . The alterations in percentage frequencies of the NPLC during tumour metastasis differ markedly from the changes in these cells in the liver during endotoxinaemia.     

Orbital surgery – perioperative problems and results

Fragestellung: Orbitotomien nehmen innerhalb der Ophthalmochirurgie auf Grund der involvierten anatomischen Strukturen und des daraus resultierenden Spektrums m?glicher perioperativer Probleme eine Sonderstellung ein. Um einen überblick über die Art und H?ufigkeit intra- und postoperativer Probleme bei Orbitotomien zu erhalten, führten wir eine retrospektive Auswertung an unserer Klinik durchgeführter Orbitotomien durch. Patienten und Methode: Es wurden 48 Orbitotomien bei 46 Patienten berücksichtigt, die zwischen 08/1995 und 02/1998 operiert wurden. Ergebnisse: Schwerwiegende intraoperative Komplikationen waren mit zwei transfusionspflichtigen Blutungen und einer Liquorfistel selten. Sie wurden interdisziplin?r behandelt. Postoperativ traten vorübergehende funktionelle St?rungen mit guter Rückbildungstendenz wie Visusminderungen (35 %), Motilit?tsst?rungen mit oder ohne Doppelbildwahrnehmung (20 %) und Lidfehlstellungen auf. Ihnen liegt v. a. die postoperative ?dem- und H?matombildung zugrunde. Persistierende Funktionseinschr?nkungen waren dagegen selten (10 %). Schlu?folgerung: Unsere Untersuchung zeigt, da? perioperativ bei Orbitotomien v. a. vorübergehende funktionelle Einschr?nkungen auftreten, die sich rasch zurückbilden. Schwere Komplikationen sind dagegen selten, treten v. a. intraoperativ auf und k?nnen eine interdisziplin?re Therapie erfordern.      

Immunosuppressive Compounds Exhibit Particular Effects on Functional Properties of Human Anti-Aspergillus TH1 Cells

Allogeneic hematopoietic stem cell transplant (HSCT) recipients are at high risk for invasive aspergillosis. Whereas adoptive immunotherapy transferring donor-derived anti-Aspergillus T_H1 cells has been shown to be beneficial for HSCT recipients suffering from invasive aspergillosis, little is known about the impact of commonly used immunosuppressants on the functional properties of anti-Aspergillus T_H1 cells. Anti-Aspergillus T_H1 cells were coincubated with different concentrations of methylprednisolone, cyclosporine (CsA), mycophenolic acid (MPA), the active component of mycophenolate mofetil, and rapamycin. Immunosuppressants were tested in concentrations reflecting common target levels in serum and in significantly lower and higher concentrations. Apoptosis of anti-Aspergillus T_H1 cells, as well as proliferation and production of gamma interferon (IFN-γ) and CD154 upon restimulation, was evaluated in the presence and absence of immunosuppressive compounds. All dosages of CsA, MPA, and methylprednisolone significantly decreased the number of viable anti-Aspergillus T_H1 cells in the cell culture, which was due partly to an impaired proliferative capacity of the cells and partly to an increased rate of apoptosis. In addition, CsA significantly decreased the number of IFN-γ-producing cells and had the highest impact of all immunosuppressants on IFN-γ levels in the supernatant. CsA also significantly decreased the expression of CD154 by anti-Aspergillus T_H1 cells. Variant dosages of immunosuppressants exhibit particular effects on essential functional properties of anti-Aspergillus T_H1 cells. Our findings may have an important impact on the design of clinical trials evaluating the therapeutic benefit of anti-Aspergillus T_H1 cells in allogeneic HSCT recipients suffering from invasive aspergillosis.     

Implants for elderly patients

In the developed world, the large birth cohorts of the so‐called baby boomer generation have arrived in medical and dental practices. Often, elderly patients are ‘young‐old’ baby boomers in whom partial edentulism is the predominant indication for implant therapy. However, the generation 85+ years of age represents a new challenge for the dental profession, as their lives are frequently dominated by dependency, multimorbidity and frailty. In geriatric implant dentistry, treatment planning is highly individualized, as interindividual differences become more pronounced with age. Nevertheless, there are four typical indications for implant therapy: (i) avoidance of removable partial prostheses; (ii) preservation of existing removable partial prostheses; (iii) stabilization of Kennedy Class I removable partial prostheses; and (iv) stabilization of complete prostheses. From a surgical point of view, two very important aspects must be considered when planning implant surgery in elderly patients: first, the consistent strive to minimize morbidity; and, second, the fact that coexisting medical risk factors are significantly more common in elderly patients. Modern three‐dimensional cone beam computed tomography imaging is often indicated in order to plan minimally invasive implant surgery. Computer‐assisted implant surgery might allow flapless implant surgery, which offers a low level of postoperative morbidity and a minimal risk of postsurgical bleeding. Short and reduced‐diameter implants are now utilized much more often than a decade ago. Two‐stage surgical procedures should be avoided in elderly patients. Implant restorations for elderly patients should be designed so that they can be modified to become low‐maintenance prostheses, or even be removed, as a strategy to facilitate oral hygiene and comfort in the final stage of life.