Percutaneous coronary intervention in the elderly: procedural success and 1-year outcomes

Clinical trials have found increased morbidity in elderly persons presenting for percutaneous coronary intervention for chronic stable angina. Long-term follow-up is limited for the elderly following percutaneous coronary intervention. The authors reviewed all coronary interventions performed from January 1998 to August 2001. One year following the procedure, subjects were screened for death, need for revascularization, and myocardial infarction. There were 401 subjects aged ≥65years (mean 73.4±6.0years) and 479 subjects aged <65years (mean 55.6±6.7 years). Although there was no difference in 1-year rate of subsequent myocardial infarction or in revascularization, the elderly were more likely to die during hospitalization (4.7% vs. 1.0%, p<0.01), and at 1 year (10.2% vs. 4.0%, p<0.01). When controlled for ejection fraction, age was no longer significant in either predischarge mortality or in 1-year mortality. Excess postpercutaneous coronary intervention mortality in the elderly may be due to underlying comorbidities and not due to subsequent myocardial infarction or revascularization.     

Input dysfunction and beyond--an evaluation of CPT components

The aim of our project is to analyze the functional meaning of neurocognitive components of the Continuous Performance Tests (CPT), which may be responsible for the well-documented performance deficit. Since the CPT can be considered as a vulnerability marker for schizophrenia, this question is of special interest. We set up a test battery testing five different cognitive processing modes: perceptual organization, selective attention, short-term memory (storing component), working memory (rehearsal component), and vigilance/sustained attention. In order to avoid the pitfall of interpreting results confounded by psychometric differences within tasks, we created psychometrically parallel versions within each experimental block (following the proposals of Chapman and Chapman [J. Nerv. Ment. Dis. 171 (1983) 658]). At the main experimental session, we tested newly admitted patients with a DSM diagnosis of schizophrenia during remission (N=30), patients with major depressive disorder (MD) (N=18), and healthy controls (N=20). Results showed that differences specific for schizophrenia are seen at the experimental block, which tests perceptual organization. However, all levels of perceptual organization performance were concerned, i.e., from processing organized to non-organized patterns. The regression analysis showed that 3-7 CPT version performances could be explained by problems with short-term memory, sustained attention, and perceptual organization. In light of these findings, we discussed whether etiology of schizophrenia could be conceptualized as a circumscribed neurocognitive deficit or a multifunctional, multilocal deficit.     

Hippocampal expression of the calcium sensor protein visinin-like protein-1 in schizophrenia

Hippocampal cytoarchitectural abnormalities may be part of the cerebral substrate of schizophrenia. Amongst the chemical components being abnormal in brains of schizophrenics are altered calcium concentrations and reduced expression of the neurotrophin receptor, trkB. We studied by immunohistochemical methods the distribution of visinin-like protein-1 (VILIP-1), which is a calcium sensor protein and at the same time a trkB mRNA binding protein, in hippocampi of nine schizophrenic patients and nine matched control subjects. In normal hippocampi VILIP-1 immunoreactivity was found in multiple pyramidal cells and interneurons. A portion of VILIP-1 immunoreactive interneurons co-express calretinin (60%) and parvalbumin (<10%). In schizophrenics fewer pyramidal cells but more interneurons were immunostained. Our data point to an involvement of the protein in the altered hippocampal circuitry in schizophrenia.     

Toward a more complete recognition of immunoreactive antigens in squamous cell lung carcinoma

There is very limited knowledge about the antibody response against tumor-expressed antigens in lung cancer. To arrive at a more complete picture of lung cancer antigens, we generated 2 cDNA libraries from squamous cell lung carcinoma and isolated 15 immunogenic antigens using autologous sera. Among the antigens most frequently identified were the lymphoid blast crisis oncogene (LBC), an unknown hypothetical protein and the p53-binding protein (TP53 BP), which have already been associated with tumor development. Of the immunogenic antigens, 6 map to chromosomes that are frequently altered in squamous cell lung carcinoma. SEREX database analysis showed that 7 of the identified immunogenic antigens have been associated with the humoral immune response in other human tumors. Screening with heterologous sera of patients with lung carcinoma identified 4 antigens, including human protein kinase C and TP53 BP, which have also been found by autologous screening. Only 1 of the 15 identified antigens reacted with any of the 36 control sera, which were taken from individuals without known disease. Sera from adenocarcinoma and large cell carcinoma of the lung were not reactive for the antigens. In summary, using 2 newly established cDNA libraries, we isolated 15 novel antigens, which were subsequently evaluated for the frequency of their corresponding antibodies in autologous, normal and heterologous sera; their chromosomal localization; and their correlation with survival after surgery.     

Docetaxel and carboplatin as second-line chemotherapy for metastatic non-small cell lung cancer

The aim of this pilot study was to evaluate the activity and toxicity of docetaxel plus carboplatin as second-line treatment in patients with metastatic non-small cell lung cancer (NSCLC). Patients received docetaxel 75 mg/m(2) followed by carboplatin AUC 5 on day 1 every 3 weeks in an out-patient setting. Twenty-six patients were enrolled; 23 patients were diagnosed stage IV disease and three patients had a IIIB disease with malignant pleural effusion. The median interval from first to second-line treatment was 3.5 months (range 1-13). Patients received a total of 101 cycles with a median number of four cycles per patient (range 1-6). Five patients achieved a partial remission (19.23%; 95% confidence interval (CI) 6.55-39.35%), 11 had stable disease (42.31%) and ten progressed (38.46%) after initiation of second-line therapy. Median survival was 243 days (95% CI 182-336 days), the median progression-free survival was 118 days (95% CI 89-170 days), and the 1-year survival rate was 25.98% (95% CI 6.33-45.63%). Moderate haematological and mild nonhaematological toxicities were observed. No treatment-related death occurred. In conclusion, docetaxel plus carboplatin as second-line regimen has a reasonable activity with good tolerance and encouraging survival data.     

The influence of the suppression of gastrooesophageal reflux on the gene expression pattern in Barrett's oesophagus

About 10% of Barrett's patients develop an adenocarcinoma in the course of life. There is increasing evidence that persistent gastrooesophageal reflux is involved in carcinogenesis. We investigated whether the gene expression pattern of Barrett's epithelium cells changes upon suppression of gastrooesophageal reflux compared to unsuppressed reflux. Biopsies from various regions of Barrett's segments and, further, during and without proton pump inhibitor therapy were collected in 5 patients. The reflux profile was assessed by simultaneous 24-h oesophageal pH and bile reflux testing. m-RNA was extracted from the specimens, and integrity and absence of DNA proven by gel electrophoresis and ALU-PCR. Using the micro array technique 1,176 genes were analysed and assigned an expression level. The number of genes detected in each experiment varied from 86 to 136. There was a 91% concordance of the gene expression pattern in distal and proximal biopsies from an individual Barrett's segment. Concordance was much less (68%) between biopsies of the same patient taken during and without proton pump inhibitor therapy. The gene expression pattern in a Barrett's oesophagus varies dependent upon different reflux situations. Other factors like the location of biopsy are of minor importance. The micro array technique allows for selection of candidate genes important in carcinogenesis.     

Dentate granule cells in reeler mutants and VLDLR and ApoER2 knockout mice

We have studied the organization and cellular differentiation of dentate granule cells and their axons, the mossy fibers, in reeler mutant mice lacking reelin and in mutants lacking the reelin receptors very low density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2). We show that granule cells in reeler mice do not form a densely packed granular layer, but are loosely distributed throughout the hilar region. Immunolabeling for calbindin and calretinin revealed that the sharp border between dentate granule cells and hilar mossy cells is completely lost in reeler mice. ApoER2/VLDLR double-knockout mice copy the reeler phenotype. Mice deficient only in VLDLR showed minor alterations of dentate organization; migration defects were more prominent in ApoER2 knockout mice. Tracing of the mossy fibers with Phaseolus vulgaris leukoagglutinin and calbindin immunolabeling revealed an irregular broad projection in reeler mice and ApoER2/VLDLR double knockouts, likely caused by the irregular wide distribution of granule cell somata. Mutants lacking only one of the lipoprotein receptors showed only minor changes in the mossy fiber projection. In all mutants, mossy fibers respected the CA3-CA1 border. Retrograde labeling with DiI showed that malpositioned granule cells also projected as normal to the CA3 region. These results indicate that ( 1 ) reelin signaling via ApoER2 and VLDLR is required for the normal positioning of dentate granule cells and (2) the reelin signaling pathway is not involved in pathfinding and target recognition of granule cell axons.     

GAS64, the first amplified and putative non-translated gene.

Gene amplification occurs frequently in human glioblastomas. We report the amplification and expression analysis of glioma amplified sequence 64 (GAS64) which was recently identified by microdissection mediated cDNA capture from the amplicon at 12q13-15. Herein we analyzed primary tumor tissues for amplification frequency and found amplification of GAS64 in 5 out of 49 glioblastomas. The amplification frequency of 10% for GAS64 found among glioblastomas is comparable to the frequency described for other genes from the 12q13-15 amplicon. To isolate the full-length cDNA of GAS64, we performed cDNA library screening and RACE. Sequence analysis of the gene revealed no open reading frame longer than 191 bp suggesting that the RNA may function as a non-translated RNA. Non-translated RNAs have been reported to function on the RNA level as regulators of gene expression. Northern hybridization of GAS64 revealed an increased GAS64 expression in many human glioblastomas with and without GAS64 gene amplification. This is the first report on an amplified and expressed gene with a short open reading frame (ORF). GAS64 may be a candidate gene for regulating gene expression in glioblastomas at the RNA level, possibly through expression of a non-translated RNA.