Oxcarbazepine reduces seizure frequency in a high proportion of patients with both newly diagnosed and refractory partial seizures in clinical practice.

The antiepileptic efficacy and tolerability of oxcarbazepine, used both as monotherapy and adjunctive therapy, were observed for 1 year in 202 adult patients, aged 17-83 years, with newly diagnosed or refractory partial epilepsy in clinical practice in Italy. At first observation, the seizure free rate was 72.2% in newly diagnosed patients given monotherapy, 40% in patients in whom oxcarbazepine replaced another monotherapy and 10.3% in patients given oxcarbazepine as adjunctive therapy. At least 50% reduction in seizure frequency was achieved in 90.7, 72 and 57%, respectively. Efficacy increased with the duration of treatment (p < 0.0001). In the 160 completers the seizure free rate was 61.3% with monotherapy and 28% with adjunctive therapy. 16.3% of patients reported adverse effects, mainly sedation and sleepiness; 5% discontinued oxcarbazepine because of adverse events. OXC is an effective and well-tolerated antiepileptic agent for the long-term treatment of partial epilepsy in adults.     

Modifying integra as a regeneration template in deep tissue planes.

Contour defects resulting in deformity caused by lack of tissue can be improved by conventional surgery using autologous tissue, but there is always a donor site morbidity. Integra has been available since the early 1980's for use in acute burns and more recently in reconstruction. It has been shown histologically to act as a tissue regeneration template. The regenerated dermis is buried under an autologous thin split-skin graft. In this study, the principle of burying Integra (without the silicone layer) has been applied to deep tissue defects in 12 reconstructive cases. Such regenerated tissues survive at least 3 years after burying. Modification to the technique to avoid visible edges are being developed.     

Within-host dynamics of antigenic variation.

Genomes of some parasites contain dozens of alternative and highly diverged surface antigens, of which only a single one is expressed in any cell. Individual cells occasionally change expression of their surface antigen, allowing them to escape immune surveillance. These switches appear to occur in a partly random way, creating a diverse set of antigenic variants. In spite of this diversity, the parasitemia develops as a series of outbreaks, in which each outbreak is dominated by relatively few antigenic types. Host-specific immunity eventually clears the dominant antigenic types, and a new outbreak follows from antigenic types that have apparently been present all along at low frequency. This pattern of sequential dominance by different antigenic types remains unexplained. We review the five most prominent theories, which have developed mainly from studies of the protozoans Trypanosoma and Plasmodium, and the bacterial spirochete Borrelia. The most promising theories depend on some combination of mechanisms to create favored connectivity pathways through the matrix of transitions between variants. Favored pathways may arise from biased switches at the molecular level of gene expression or from biases imposed by immune selection. We illustrate the concept of connectivity pathways by reanalysis of data on transitions between variants from Borrelia hermsii.     

Operationsrisiko nach neoadjuvanter Therapie gastrointestinaler Karzinome

Zusammenfassung Viele gastrointestinale Tumoren werden im Rahmen multimodaler Therapiekonzepte behandelt. Für den Chirurgen ist die neoadjuvante, präoperative Behandlung von besonderem Interesse, da sie durch therapiebedingte Nebenwirkungen und Komplikationen zu einer Beeinflussung des postoperativen Verlaufs führen kann. Die neoadjuvante Radiochemotherapie ist fester Bestandteil der Therapie beim primären T4-Rektumkarzinom, beim Rektumkarzinomrezidiv und bei tief sitzenden primären Rektumkarzinomen. Durch Erhöhung der R0-Resektionsrate können die lokale Tumorkontrolle verbessert und die Überlebenszeit verlängert werden. Die postoperative Komplikationsrate ist dabei nicht wesentlich erhöht. In der Behandlung des primär resektablen Ösophaguskarzinoms deutet sich ein Vorteil der neoadjuvanten Radiochemotherapie im Vergleich zur alleinigen Chirurgie an. Beim lokal fortgeschrittenen Ösophaguskarzinom bietet die präoperative Radiochemotherapie häufig die einzige Chance zur Resektion, jedoch mit einer deutlich erhöhten postoperativen Morbidität und Mortalität. Die Wirksamkeit und Sicherheit einer neoadjuvanten Chemo- oder kombinierten Radiochemotherapie beim fortgeschrittenen Magenkarzinom wird derzeit im Rahmen von Studienprotokollen untersucht.     

BCR-ABL activity and its response to drugs can be determined in CD34+ CML stem cells by CrkL phosphorylation status using flow cytometry.

In chronic myeloid leukaemia, CD34(+) stem/progenitor cells appear resistant to imatinib mesylate (IM) in vitro and in vivo. To investigate the underlying mechanism(s) of IM resistance, it is essential to quantify Bcr-Abl kinase status at the stem cell level. We developed a flow cytometry method to measure CrkL phosphorylation (P-CrkL) in samples with <10(4) cells. The method was first validated in wild-type (K562) and mutant (BAF3) BCR-ABL(+) as well as BCR-ABL(-) (HL60) cell lines. In response to increasing IM concentration, there was a linear reduction in P-CrkL, which was Bcr-Abl specific and correlated with known resistance. The results were comparable to those from Western blotting. The method also proved to be reproducible with small samples of normal and Ph(+) CD34(+) cells and was able to discriminate between Ph(-), sensitive and resistant Ph(+) cells. This assay should now enable investigators to unravel the mechanism(s) of IM resistance in stem cells.     

Pre-eclampsia is associated with sleep-disordered breathing and endothelial dysfunction.

Pre-eclamptic toxaemia (PET) may be associated with both endothelial dysfunction (ED) and sleep-disordered breathing (SDB). It was hypothesised that females with PET would demonstrate both SDB and ED, and that a correlation between these two would suggest a potential causative association. A total of 17 females with PET and 25 matched females with uncomplicated pregnancy were studied. They underwent a nocturnal ambulatory sleep study (using Watch_PAT100) and noninvasive evaluation of endothelial function utilising the reactive hyperaemia test (using Endo_PAT 2000). A higher ratio of post- to pre-occlusion pulse-wave amplitude (endothelial function index (EFI)) indicated better endothelial function. Females with PET had a significantly higher respiratory disturbance index (RDI) and lower EFI than controls (18.4+/-8.4 versus 8.3+/-1.3.h(-1), and 1.5+/-0.1 versus 1.8+/-0.1, respectively). Blood pressure significantly correlated with RDI and with EFI. EFI tended to correlate with RDI. In conclusion, these results suggest that both sleep-disordered breathing and endothelial dysfunction are more likely to occur in females with pre-eclamptic toxaemia than in females with uncomplicated pregnancies. The current authors speculate that respiratory disturbances contribute to the functional abnormality of the blood vessels seen in females with pre-eclamptic toxaemia, although causality cannot be determined based on this study.