Cerebellar haemorrhage and tension pneumocephalus after resection of a Pancoast tumour.

We present an unusual case of cerebellar haemorrhage followed by tension pneumocephalus several days after thoracotomy for resection of a Pancoast tumour. The postoperative course of the 32-year-old patient was complicated by a cerebellar haemorrhage and hydrocephalus caused by compression of the fourth ventricle. Immediate surgical evacuation of the haemorrhage and placement of an external ventricular drain was performed. Respirator ventilation maintaining a continuous positive airway pressure was required. Following weaning and extubation the patient rapidly deteriorated and became comatose. A cranial CT scan revealed a dilated ventricular system filled with air, and air in the subarachnoid space. Recovery of consciousness was observed after aspiration of intracranial air through the ventricular drainage. Recurrent deterioration of consciousness after repeated air aspiration indicated rapid refilling of the ventricles with air. The patient underwent emergency surgical re-exploration of the thoracic resection cavity: dural lacerations of the cervico-thoracic nerve roots C8 and Th1 were identified. Subarachnoid-pleural fistula, cerebellar haemorrhage and tension pneumocephalus after discontinuation of continuous positive airway pressure respiration are unusual complications of thoracic surgery. We discuss the putative pathomechanisms and present a brief review of the literature.

Inhibition of the arachidonic acid metabolism blocks endothelial cell migration and induces apoptosis.

Previous studies have demonstrated that inhibitors of the arachidonic acid metabolism block migration and sensitise human glioma cells to treatment inducing apoptosis. This paradigm may provide a new concept for anti-invasive treatment strategies targeting invasive glioma cells. However, the effect of such treatment on other cellular elements in glial tumours such as endothelial cells is unknown. In this study we have analysed the expression of metabolites of the arachidonic acid pathway in endothelial cells in vitro and in vivo and we have assessed the influence of inhibitors of this pathway on motility, capillary like tube formation, and apoptosis in human endothelial cells. Human endothelial cells (HUVEC) in culture showed expression for thromboxane synthase and both isoforms of cyclo-oxygenase, COX-1 and COX-2. Immunostaining demonstrated low levels of COX-1 expression in capillaries and larger vessels of normal brain and moderately elevated levels of this enzyme in small vessels of brain tumours of various grades. Both thromboxane synthase and COX-2 expression was limited to endothelial cells found in anaplastic gliomas and glioblastomas. Thromboxane synthase inhibitors strongly decreased endothelial cell migration in HUVEC in vitro and capillary like tube formation was strongly inhibited by the compound at a similar dose range. The non-selective cyclo-oxygenase inhibitor ASA and the selective COX-2 inhibitor sulindac only had a minor effect on endothelial cell migration, however, the COX-2 inhibitor sulindac showed a synergistic effect with the thromboxane synthase inhibitor. Thromboxane synthase inhibitors induced apoptosis in endothelial cells as demonstrated by intracellular histone-complexed DNA fragmentation. These data suggest that inhibitors of thromboxane synthase influence migration and apoptosis in both human glioma cells and human endothelial cells. An anti-invasive treatment strategy using this class of compounds may therefore not only sensitise glioma cells to conventional treatments inducing apoptosis but may also be supported by an anti-angiogenic effect.

Association analysis of exonic variants of the gene encoding the GABAB receptor and alcohol dependence.

The present association study tested whether genetic variation of the GABAB receptor (GABABR1) gene confers vulnerability to alcohol dependence. The genotypes of three DNA sequence variants in exons 1a1, 7 and 11 of the GABABR1 gene were assessed in 234 German controls and 350 German alcohol-dependent subjects, including three more homogeneous subgroups of alcoholics, marked by (1) history of parental alcoholism (n = 121); (2) history of alcohol withdrawal seizure or delirium (n = 108); and (3) comorbidity of dissocial personality disorder (n = 60). The allele frequencies of none of the investigated GABABR1 variants differed significantly between the controls and the groups of alcoholics when a correction for multiple testing was taken into account (P > 0.004). However, trends (P < 0.10) towards an excess of the Ser489 allele of the exon 7 polymorphism were found in the subgroups of alcoholics, and of the common allele of the exon 11 polymorphism in the entire sample of alcoholics (P = 0.032), alcoholics with parental alcoholism (P = 0.084) and the dissocial alcoholics (P = 0.037). Our findings suggest that the investigated GABABR1 variants do not contribute a substantial effect (RR > 3) to the genetic variance of alcohol dependence. Nevertheless, the hints towards potential allelic associations of the exon 7 and 11 polymorphisms with dissocial alcoholism emphasize further studies to test more defined phenotype-genotype relationships.

Lack of an allelic association between polymorphisms of the dopamine D2 receptor gene and alcohol dependence in the German population.

Our study examined recent claims of an association of the TaqI A1 allele and the functional -141C Ins allele of the dopamine D2 receptor (DRD2) gene with alcohol dependence. Genotypes of the TaqI A and -141C insertion/deletion polymorphisms were assessed in 196 German nonalcoholic controls and 310 German alcohol-dependent subjects, including two more homogeneous subgroups selected by either a history of parental alcoholism (n = 108) or by a history of severe physiological alcohol withdrawal symptoms (n = 99). We found no association between any of the biallelic variants or the A1/Ins haplotype and alcohol dependence (p > 0.05). Our present association results failed to replicate evidence that either the TaqI A1 allele or the functional Ins allele or the A1/Ins haplotype of the DRD2 gene confers vulnerability to alcohol dependence in the German population.