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.     

Flumazenil exerts intrinsic activity on sleep EEG and nocturnal hormone secretion in normal controls

The physiological function of benzodiazepine (BDZ) receptors includes regulation of sleep and neuroendocrine activity. Most of the pharmacological effects of BDZ are blocked by flumazenil. However, recent neurological and behavioral studies suggest that flumazenil has its own central intrinsic activity. This issue was addressed in a study of the sleep EEG and the nocturnal secretion of growth hormone and cortisol in ten normal male controls, who were given flumazenil either alone or in combination with the BDZ agonist midazolam, placebo and midazolam alone. Flumazenil prompted an increase in sleep onset latency, a decrease in slow wave sleep and an increase in wakefulness. Plasma cortisol concentrations after flumazenil administration were lower than after midazolam. Both flumazenil and midazolam decreased nocturnal growth hormone secretion. After simultaneous application of both BDZ receptor ligands the growth hormone blunting was amplified. Our study demonstrates that at the level of the sleep EEG and neuroendocrine activity flumazenil is capable of exerting both agonistic and inverse agonistic or antagonistic effects.Parts of this study were presented at the 69th Meeting of the Deutsche Physiologische Gesellschaft, Freiburg, 6–8 March, 1991     

Sleep EEG effects of 3,4-methylenedioxyethamphetamine (MDE; "eve") in healthy volunteers.

3,4-methylenedioxyethamphetamine (MDE; "Eve") exerts similar psychotropic effects in humans as 3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") and is less toxic in animal studies. We conducted a double-blind, placebo-controlled, cross-over sleep electroencephalogram (EEG) study with healthy volunteers. One hundred forty milligrams of MDE or placebo were administered PO in six subjects at 11 PM. Sleep EEG was registered from 11 PM-7 AM the next morning. All subjects had a normal sleep onset latency. They all awoke 60 to 120 min after administration of MDE and stayed awake for at least 150 min (total sleep time, TST MDE < placebo and intermittent time awake MDE > placebo: p < 0.001). After again falling asleep rapid eye movement (REM) sleep was totally suppressed (REM during time in bed, TIB MDE < placebo: p < 0.001). A cyclic alternation of relatively long periods of slow wave sleep (SWS) with periods of light sleep occurred in three subjects during the second part of the night (stage 4 in second part of night MDE > placebo: p = 0.16). The effects of MDE on sleep variables largely demonstrate the stimulant, amphetamine-like properties of MDE.     

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.     

Involvement of two genes of superinfecting phage Kappa in curing and induction of prophage Psi in Serratia marcescens HY

Prophage Ψ carried along with prophage y by Serratia marcescens HY is subject of moderate curing at heteroimmune superinfection of cells from stationary phase with phage χ. Curing becomes considerably more frequent when the bacteria are non-iysogenic for y. Both Ψ, y-double-lysogenic and Ψ-single-lysogenic cells with a mutation in the ink gene are very efficiently cured of Ψ if infected by χtay, although this mutant was characterized as being deficient in transactivation of certain genes in prophage y. On the other hand to get efficiently cured after χ wild-type infection these cells too must be devoid of a y prophage. Thus a y function turned on by tay⁺ seems to counteract the elimination of Ψ. However, interestingly enough Ψ curing is boosted by a further y function under special circumstances. Efficient curing depends on an intact χtap gene, a gene reported to cause transactivation of certain Ψ genes. Curing at χtay infection is specifically accompanied by induction of the Ψ prophage in a part of the infected cells. However, there is no such induction at χ wild-type infection, either in the absence or presence of a y prophage. An explanation of these findings is suggested which includes an antirepressive effect exerted on Ψ and a hypothetical interaction between the products of genes tap and tay.     

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.     

Short- and long-term impact of neutropenia within the first year after kidney transplantation

The aim of this retrospective single-center study was to investigate the short- and long-term impact of neutropenia occurring within the first year after kidney transplantation, with a special emphasis on different neutropenia grades. In this unselected cohort, 225/721 patients (31%) developed 357 neutropenic episodes within the first year post-transplant. Based on the nadir neutrophil count, patients were grouped as neutropenia grade 2 (<1.5–1.0*10⁹/l; n = 105), grade 3 (<1.0–0.5*10⁹/l; n = 65), and grade 4 (<0.5*10⁹/l; n = 55). Most neutropenia episodes were presumably drug-related (71%) and managed by reduction/discontinuation of potentially responsible drugs (mycophenolic acid [MPA] 51%, valganciclovir 25%, trimethoprim/sulfamethoxazole 19%). Steroids were added/increased as replacement for reduced/discontinued MPA. Granulocyte colony-stimulating factor was only used in 2/357 neutropenia episodes (0.6%). One-year incidence of (sub)clinical rejection, one-year mortality, and long-term patient and graft survival were not different among patients without neutropenia and neutropenia grade 2/3/4. However, the incidence of infections was about 3-times higher during neutropenia grade 3 and 4, but not increased during grade 2. In conclusion, neutropenia within the first year after kidney transplantation represents no increased risk for rejection and has no negative impact on long-term patient and graft survival. Adding/increasing steroids as replacement for reduced/discontinued MPA might supplement management of neutropenia.