Risk of cancer in patients with Guillain-Barré syndrome (GBS)

Abstract. The possible relationship between Guillain-Barré syndrome (GBS) and cancer is still controversial and the existence of a paraneoplastic GBS remains unconfirmed. To better define whether there is a relationship between GBS and malignancy, we compared the observed and the expected number of patients with tumours in a population-based cohort of subjects with GBS. Clinical differences between GBS patients with or without malignancies were analysed. Data were obtained from the Piemonte and Valle dAosta Register for GBS (PARGBS) (years 1990–1998). GBS was diagnosed according to NINCDS criteria. The number of expected cases of malignancy in the PARGBS population was calculated using the incidence rate of all types of cancer (ICD codes 140–208) in Piemonte [1985–1987], and in the most important town of this region, that is Turin (years 1993–1997). In the nine-year period, 435 incident patients with GBS were found. Nine of them developed cancer in the six months preceding or following GBS; in seven of them, the diagnosis of cancer and GBS was concomitant. The expected number of malignant tumours was 3.7 (using the incidence in Piemonte) and 3.8 (using the incidence in Turin); therefore, the odds ratios were 2.43 (95 % CI, 1.11–4.62) and 2.37 (95% CI, 1.09–4.50), respectively (p < 0.01). Although the cases with malignancies were clinically similar to the other cases of GBS observed through the Register, the mortality in GBS patients with cancer was higher and was the final cause of death in two patients affected by severe cancer. These results suggest a possible correlation between some cases of GBS and cancer. However, GBS in cancer patients does not meet all the criteria for paraneoplastic diseases.* Piemonte and Valle dAosta Register for GBS (PARGBS): Coordinating center: 2^nd Division of Neurology, Department of Neuroscience, University of Torino, Italy. Project coordinator: A. Chiò, MD. Study monitors: A. Calvo, MD, N. Di Vito, MD, M. Vercellino, MD. Scientific Committee: A. Bertolotto, MD, E. Bottacchi, MD, A. Chiò, MD, D. Cocito, MD, M. T. Giordana, MD, M. Leone, MD, L. Mazzini, MD, G. Mora, MD. Collaborating centers: A. Chiò, MD, A. A. Terreni, MD, D. Schiffer, MD, R. Mutani, MD, D. Cocito, MD, B. Bergamasco, MD, I. Rainero, MD (Department of Neuroscience, Section of Neurology, University of Torino, and Azienda Ospedaliera San Giovanni Battista, Torino), A. Bertolotto, MD, A. Tribolo, MD, R. Sciolla, MD, F. Mondino, MD, M. T. Giordana, MD (Department of Neuroscience, Section of Neurology, University of Torino, and Azienda Ospedaliera San Luigi Gonzaga, Orbassano), M. Leone, MD, P. Gaviani, MD, F. Monaco, MD (Department of Neurology, Amedeo Avogadro University, Novara), M. De Mattei, MD, E. Morgando, MD (Department of Neurology, Azienda Ospedaliera San Giovanni, Torino), L. Sosso, MD, M. Gionco, MD (Department of Neurology, Ospedale Mauriziano, Torino), U. Morino, MD, M. Nobili, MD (Department of Neurology, Ospedale Martini, Torino), L. Appendino, MD (Department of Neurology, Ospedale Maria Vittoria, Torino), D. Piazza, MD (Department of Neurology, Ospedale S. Giovanni Bosco, Torino), E. Oddenino, MD, W. Liboni, MD (Department of Neurology, Ospedale Gradenigo, Torino), G. Vaula, MD, G. Ferrari, MD (Department of Neurology, Ivrea), M. Favero, MD, C. Doriguzzi Bozzo, MD (Department of Neurology, Pinerolo), P. Santamaria, MD (Department of Neurology, Vercelli), U. Massazza, MD, E. Bollani, MD (Department of Neurology, Biella), A. Villani, MD, R. Conti, MD (Department of Neurology, Domodossola), G. Mora, MD, C. Balzarini, MD (Department of Neurological Rehabilitation, Fondazione S. Maugeri, Clinica del Lavoro e della Riabilitazione, IRCCS, Scientific Institute of Veruno), M. Palermo, MD (Department of Neurology, Alessandria), F. Vergnano, MD (Department of Neurology, Casale Monferrato), S. Cordera, MD, C. Buffa, MD (Department of Neurology, Novi Ligure), M. T. Penza, MD (Department of Neurology, Tortona), F. Fassio, MD (Department of Neurology, Asti), P. Meineri, MD (Department of Neurology, Azienda Ospedaliera Santa Croce e Carle, Cuneo), A. Cognazzo, MD, C. Mocellini, MD, A. Dutto, MD, A. Cucatto, MD (Department of Neurology, Savigliano), C. Cavestro, MD, W. Troni, MD (Department of Neurology, Alba), G. Corso, MD, E. Bottacchi, MD (Department of Neurology, Aosta).     

Paralytic ileus in MELAS with phenotypic features of MNGIE

This report describes a child having the syndrome of overlapping phenotypic features of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE). Mitochondrial DNA analysis revealed a point mutation at position A3243G, whereas activity of thymidine phosphorylase and its corresponding gene analysis were normal. The most striking feature of this case was paralysis of one segment of the terminal ileum observed on laparotomy. The electron microscopic findings of the resected ileum and colon by limited right hemicolectomy disclosed accumulation of numerous enlarged mitochondria with ill-defined cristae which were similar to mitochondria reported in three previous MELAS cases and one MNGIE case with intestinal dysmotility. We emphasize that the MELAS and MNGIE phenotypes overlapped in this case and that the mechanism of acute ileus in MELAS was associated with functional paralysis of the intestine.     

A randomized controlled trial of a specific reminiscence approach to promote the well-being of nursing home residents with dementia

BACKGROUND: To date, no firm conclusions can be reached regarding the effectiveness of reminiscence for dementia. Researchers have emphasized that there is an urgent need for more systematic research in the area. OBJECTIVE AND METHOD: A single-blinded, parallel-groups (one intervention, one comparison, and one no-intervention group) randomized controlled trial (RCT) was adopted to investigate whether a specific reminiscence program leads to higher levels of psychosocial well-being in nursing home residents with dementia. The intervention adopted a life-story approach, while the comparison group provided friendly discussions to control for any changes in outcome as a result of social contacts and attention. The Social Engagement Scale (SES) and Well-being/Ill-being Scale (WIB) were the outcome measures used. The outcomes of the groups were examined with reference to the baseline (T0), immediately (T1), and six weeks (T2) after intervention. The final sample had 101 subjects (control group: n=30; comparison group: n=35; intervention group: n = 36). Using multivariate analysis with repeated measures, no significant differences in outcome were found between groups at either T1 or T2. Wilcoxon signed rank tests were performed for each group comparing outcomes between T1 and T0, T2 and T1, and T2 and T0. Significant differences were observed in the intervention group when comparing T1 and T0 WIB (p = .014), but not for the other groups. CONCLUSION: Although the intervention did not lead to significant differences between the three groups over time, there was a significant improvement in psychosocial well-being for the intervention group.     

Percutaneous radiological gastrostomy: a safe and effective method of nutritional tube placement in advanced ALS

BACKGROUND: Enteral nutrition may be required in amyotrophic lateral sclerosis (ALS), and is usually achieved by percutaneous endoscopic gastrostomy (PEG). As PEG is not indicated in patients with severe respiratory impairment, an alternative is percutaneous radiological gastrostomy (PRG), involving air insufflation into the stomach under fluoroscopic guidance for tube insertion. OBJECTIVE: To evaluate the safety of PRG and its effect on survival and respiratory function in ALS patients with respiratory failure. METHODS: 25 consecutive ALS patients with severe dysphagia and forced vital capacity (FVC) <50% underwent PRG after October 2000. They were compared with 25 consecutive ALS patients with FVC <50% who underwent PEG before October 2000. Respiratory function was evaluated before and after the procedure. RESULTS: The two groups were similar for all relevant characteristics. PRG was successful in all cases, PEG in 23/25. One patient in each group died after the procedure. The mean survival time after the procedure was 204 days in the PRG group and 85 days in the PEG group (p<0.004). Respiratory function decreased more in the PEG group than in the PRG group (p<0.02). CONCLUSIONS: PRG appears to be safer than PEG in ALS patients with moderate or severe respiratory impairment, and is followed by a longer survival.     

ApoE epsilon4 allele is associated with incidental hallucinations and delusions in patients with AD

Of 135 patients with Alzheimer disease (AD), 56 without psychiatric symptoms at the first visit were followed for a mean period of 51.9 +/- 10.3 months to identify incident psychiatric symptoms. The hazard ratios of ApoE epsilon4 allele in developing psychiatric symptoms were calculated by Cox regression hazard analyses. The presence of the ApoE epsilon4 allele carried a 19.0-fold risk for developing hallucinations and a 3.4-fold risk for delusions.     

Identification of the main human cytochrome P450 enzymes involved in safrole 1'-hydroxylation

Safrole is a natural plant constituent, found in sassafras oil and certain other essential oils. The carcinogenicity of safrole is mediated through 1'-hydroxysafrole formation, followed by sulfonation to an unstable sulfate that reacts to form DNA adducts. To identify the main cytochrome P450 (P450) involved in human hepatic safrole 1'-hydroxylation (SOH), we determined the SOH activities of human liver microsomes and Escherichia coli membranes expressing bicistronic human P450s. Human liver (n = 18) microsomal SOH activities were in the range of 3.5-16.9 nmol/min/mg protein with a mean value of 8.7 +/- 0.7 nmol/min/mg protein. In human liver (n = 3) microsomes, the mean K(m) and V(max) values of SOH were 5.7 +/- 1.2 mM and 0.14 +/- 0.03 micromol/min/nmol P450, respectively. The mean intrinsic clearance (V(max)/K(m)) was 25.3 +/- 2.3 microL/min/nmol P450. SOH was sensitive to the inhibition by a CYP2C9 inhibitor, sulfaphenazole, and CYP2E1 inhibitors, 4-methylpyrazole and diethyldithiocarbamate. The liver microsomal SOH activity showed significant correlations with tolbutamide hydroxylation (r = 0.569) and chlorzoxazone hydroxylation (r = 0.770) activities, which were the model reactions catalyzed by CYP2C9 and CYP2E1, respectively. Human CYP2C9 and CYP2E1 showed SOH activities at least 2-fold higher than the other P450s. CYP2E1 showed an intrinsic clearance 3-fold greater than CYP2C9. These results demonstrated that CYP2C9 and CYP2E1 were the main P450s involved in human hepatic SOH.     

Cytotoxicity of Triamcinolone on Cultured Human Retinal Pigment Epithelial Cells: Comparison with Dexamethasone and Hydrocortisone

Purpose Triamcinolone acetonide (TA) is a corticosteroid that can be used in the treatment of cystoid macular edema (CME) and other ocular inflammatory conditions. This study aims to investigate the degree of cytotoxic effect of TA on human retinal pigment epithelium (ARPE19 cell line) and to compare the relative toxicity of TA with two other corticosteroids, hydrocortisone (HC) and dexamethasone (DEX), over a range of concentrations and durations of exposure.Methods The ARPE19 cell line was cultured and maintained in a 1:1 mixture of Dulbeccos modified Eagles medium and HAMS F12 medium containing 3mM l-glutamine supplemented with 10% fetal bovine serum, penicillin G, and streptomycin sulfate. Following an initial overnight incubation, corticosteroids (0.01–1mg/ml) or vehicle (benzyl alcohol, 0.025%), diluted in culture medium, was added to the ARPE19 culture (5000 cells/well) on Day 0. Subsequently the culture medium containing corticosteroid or vehicle was refreshed daily. After 1, 3, and 5 days, the proliferated amount of cells with and without corticosteroid treatment was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. All samples were read in triplicate, with n = 4 in all cases. The final results were analyzed using analysis of variance.Results TA, DEX, and HC caused a significant reduction in cell numbers throughout the whole range of concentrations when cells were exposed to them for more than one day. The action of the corticosteroids, apart from TA, was biphasic. There was an initial rise in cell proliferation in the presence of DEX and HC at 0.01–0.1mg/ml on Day 1. Log-linear plots of DEX and HC concentrations against percent viability (mean % ± SD) showed a significantly higher total viable cell percentage versus TA: 120.5 ± 1.8% and 134.9 ± 4.1% in the presence of DEX, and 110.0 ± 15.3% and 118.3 ± 9.0% in the presence of HC. The LD₅₀ values of the three corticosteroids show that, regardless of the duration of exposure, TA was the most toxic, with relative toxicity of TA > DEX > HC, equivalent to a ratio of 1.0:1.6:1.8, after one day of incubation. The vehicle alone had no effect.Conclusions The present study demonstrated the degree of cytotoxicity of TA compared with DEX and HC. The results provide a profile of this drug relative to other common corticosteroids. Further studies are planned to characterize its effects and the degree of influence on cells of different ocular regions in order to show the full cytotoxicity of TA. Jpn J Ophthalmol 2004;48:236–242 © Japanese Ophthalmological Society 2004     

茶多酚、茶色素对人肝癌细胞株HepG2端粒酶活性的影响

目的　利用人肝癌细胞株HepG2观察茶多酚和茶色素对端粒酶活性的影响。方法采用TRAP PCR ELISA方法对HepG2细胞端粒酶活性进行定性和定量检测。结果　TRAP PCR定性分析表明空白对照组、茶多酚组和茶色素组均端粒酶阳性 ;ELISA定量结果显示 ,5 0mg/L和 10 0mg/L茶多酚组端粒酶活性 (A450 690 值 )分别为 1 5 6和 1 4 6 ;5 0mg/L和 10 0mg/L茶色素处理组为 1 5 5和1 4 9,与空白对照组 (A450 690 值为 2 11)相比 ,茶多酚和茶色素处理后HepG2细胞端粒酶活性有统计学意义。结论　茶多酚和茶色素显著抑制HepG2细胞端粒酶活性 ,端粒酶活性可能是癌症化学预防研究的一个有用的生物标志物     

Eicosapentaenoic acid induces Fas-mediated apoptosis through a p53-dependent pathway in hepatoma cells

Eicosapentaenoic acid (EPA) has been demonstrated to induce apoptosis and cell cycle arrest in various cancer cell lines in vitro. In this study, we investigated the anti-tumor effects of EPA on hepatoma cell lines and the mechanisms responsible for induced cell death. Three hepatoma cell lines tested had different p53 status: HepG2 with a wild-type p53; Hep3B, of which the endogenous p53 was deleted; and Huh7 with its p53 mutated. MTT assay showed reduced viability of HepG2 cells after exposure to EPA, and the cytotoxicity of EPA was time and dose dependent. However, EPA had no effect on the viability and cell death in the two other hepatoma cell lines containing dysfunctional p53. DNA fragmentation analysis and TUNEL (terminal deoxynucleotidyl transferase [TdT]-mediated deoxyuridine diphosphate [dUTP] nick end labeling) staining showed a typical pattern of DNA laddering and DNA breaks staining, respectively, in wild-type p53-containing HepG2 cells after EPA treatment. We also observed that EPA induced transient nuclear accumulation of P53 protein that subsequently up-regulated the expression of Fas messenger RNA and protein in HepG2 cells. In contrast, these findings were not observed in Hep3B and Huh7 cells exposed to EPA. Most notably, EPA-induced apoptosis in HepG2 cells could be reduced almost completely by treatment with FasL antisense oligonucleotides. We conclude that EPA inhibits the growth of HepG2 cells and mediates its effect, at least in part, via the Fas-mediated apoptosis. It appears that the effects of EPA on hepatoma cells are determined by the status of p53 and that wild-type p53 is a prerequisite for the anticancer effect of EPA.