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Biomedical subjects

M Ziol

Publications and source records attributed to M Ziol.

At least 19 recordsLinked to original sources
PubMed2006

Routine surgical pathology in general surgery.

BACKGROUND: Although pathological analysis provides the definitive diagnosis for most resection specimens, recent evidence suggests that such analysis may be omitted for certain routine samples. This was a retrospective analysis of the value of routine histopathological examination performed in daily general surgical practice. METHODS: All specimens from routine appendicectomies, cholecystectomies, haemorrhoidectomies and inguinal hernia repairs performed between 1993 and 2002 were included. The analysis included a comparison of histological and macroscopic diagnoses, review of preoperative and peroperative findings, and an evaluation of the consequences of routine histopathological assessment on patient management and costs. RESULTS: With the exception of hernia specimens, the rate of submission for routine pathological evaluation was 100 per cent. No hernia sac specimen from more than 2000 interventions revealed aberrant histological findings. Of 311 haemorrhoidectomy specimens three showed malignancy, all of which had a suspicious macroscopic appearance. Of 1465 appendices, only one (0.1 per cent) had a potentially relevant histological diagnosis that was not suspected macroscopically. Among 1523 cholecystectomy specimens, all adenomas (0.6 per cent) and carcinomas (0.4 per cent) were suspected macroscopically or developed in association with a known disease. CONCLUSION: The rarity of incidental histological findings relevant to patient management, especially in the absence of macroscopic abnormalities, suggests that routine histological examination of certain specimens may be omitted. A more elementary role for macroscopic examination of the specimen by the surgeon and the pathologist is proposed.

Appendectomy↗
PubMed2006

Interferon gamma-secreting HCV-specific CD8+ T cells in the liver of patients with chronic C hepatitis: relation to liver fibrosis--ANRS HC EP07 study.

Little is known about the role of specific hepatitis C virus (HCV) CD8+ T cells in liver damage, especially for the progression of fibrosis, during the highly variable course of chronic C hepatitis. The aim of this study was to investigate the presence of HCV-specific CD8+ T cells in the liver of patients with chronic C hepatitis and to examine their clinical significance by relating the response to liver fibrosis and progression rate, serum viral load, serum aminotransferase levels, inflammatory activity and in situ characteristics of the intrahepatic infiltrate. Fifteen patients were prospectively included in the study. Intrahepatic lymphocytes were tested for interferon gamma (IFNg) production in response to HCV class I-restricted epitopic peptides using enzyme-linked immunospot analysis. Liver biopsy samples were evaluated for fibrosis, fibrosis progression rate, activity, and in situ number of CD8+ cytotoxic lymphocytes and apoptotic cells. An IFNg-specific CD8+ T-cell response was detected in the liver samples of 47% of patients which was significantly related to a lower stage of fibrosis (P = 0.02) and a lower progression rate of fibrosis (P = 0.01). It was neither related to the number of cytotoxic lymphocytes infiltrating the liver nor to hepatocyte apoptosis. In conclusion, our results indicate that the presence of HCV-specific IFNg-secreting T cells in the liver of patients with chronic C hepatitis is associated with low liver fibrosis and fibrosis progression rate, suggesting that these IFNg-secreting T cells might limit the progression of liver damage.

Adult↗
PubMed2001

Clinical and biological relevance of hepatocyte apoptosis in alcoholic hepatitis.

BACKGROUND/AIMS: Although human and experimental studies have shown that apoptosis plays a role in hepatocyte death in alcoholic liver disease, its clinical and biological significance has not been investigated in alcoholic hepatitis (AH). The aim of this study was to quantify hepatocyte apoptosis in AH and to attempt to relate it to the clinical and biological severity of the disease. METHODS: The hepatocyte apoptotic index was determined using a double in situ transferase-mediated dUTP nick end (TUNEL) and CD15 (neutrophils) labelling on 35 liver biopsies from patients with AH lesions of different severities. The specificity of TUNEL labelling for apoptosis was monitored both by morphology and fractin (a caspase actin cleavage site) immunostaining. RESULTS: The hepatocyte apoptotic index ranged from 0.3 to 28% and was related to the severity of alcoholic hepatitis as measured by the Maddrey score (P < 0.05; Mann-Whitney test) while ballooning (which reflects hepatocytes potentially undergoing necrosis) and neutrophil indexes were not. CONCLUSIONS: This suggests that hepatocyte apoptosis could be a therapeutic target to treat or to prevent alcoholic hepatitis in cirrhotic patients. Co-localization of apoptotic hepatocytes with neutrophils and the strong quantitative correlation would suggest an apoptosis dependent transmigration of neutrophils.

Actins↗
PubMed2001

Regression of primary hepatocarcinoma in cancer-prone transgenic mice by local interferon-gamma delivery is associated with macrophages recruitment and nitric oxide production.

The clinical potential of tumor therapies must be evaluated using animal models closely resembling human cancers. We investigated the impact of locally delivered interferon-gamma (IFN-gamma) on primary hepatocarcinoma spontaneously developed by T-SV40 transgenic mice. A single intratumor injection of adenovirus IFN-gamma was sufficient enough to induce in vivo production of biologically active IFN-gamma, as assessed by STAT1 activation. IFN-gamma secretion led to the regression of primary tumor, principally by apoptosis of tumor hepatocytes. The lack of T-cells infiltrates in the liver upon treatment excluded a role of a specific immune response. In contrast, indirect pathways may include tumoricidal function of macrophages. Indeed, they were massively recruited in the entire liver under IFN-gamma treatment; transmigration through hepatic blood vessels could be observed and co-localization with damaged hepatocytes was obvious. This correlated with nonparenchymal liver cell iNOS expression and high level of NO in hepatic extracts. Moreover, in vitro experiments showed that NO releasing agents induced cell death of freshly isolated tumor hepatocytes, suggesting that NO could be one of the major effector molecules. Altogether, these observations defined an important role of IFN-gamma in controlling tumor development in a model of primary hepatocarcinoma.

Adenoviridae↗
PubMed2001

[Sarcoidosis and the liver].

During systemic sarcoidosis, the liver is involved in about 66% of cases, usually clinically silent. The laboratory abnormalities include hypergammaglobulinemia and moderate increases in serum alkaline phosphatase activity; Imaging findings are extremely rare. As in the other organs, liver sarcoidosis is characterized histopathologically by epithelioid, typically noncaseating granulomas generally scattered widely, but many tend to be portal or periportal. In rare instances, liver sarcoidosis is complicated by portal hypertension or chronic cholestasis. Corticosteroids are the main treatment, indicated in case of symptomatic liver involvement and/or in case of extensive liver fibrosis. When portal hypertension is developed, specific treatment of esophageal varices is required.

Adult↗
PubMed2001

[Looking for large-cell dysplasia in liver needle biopsies how and why?].

Liver large cell dysplasia (LCD) is identifiable only at the microscopic level as foci of large hepatocytes with pleomorphic hyperchromatic nuclei and prominent nucleoli. LCD is mainly observed in cirrhotic livers, on surgical specimens, within macroregenerative nodules or low grade dysplastic nodules but also on liver needle biopsies. For needle biopsies, the prevalence of LCD ranges between 15% and 20%. in case of associated hepatocellular carcinoma, the prevalence is around 40%. LCD is more frequent in hepatitis B virus-induced liver cirrhosis than in cirrhosis related to other causes. Two prospective studies showed that LCD is a predictive factor for the occurrence of hepatocellular carcinoma in cirrhotic patients. Nevertheless LCD is probably not a precancerous lesion; dysplastic hepatocytes are biologically senescent polyploid cells unable to carry out normal cell division. Diagnosis of LCD on liver needle biopsy is indicative for the presence of large and numerous foci of LCD within the whole parenchya and allows consequently to select cirrhosis associated with advanced liver cell secescence, i.e. cirrhosis in which multistep genetic alterations of liver cell carcinogenesis could have happened with the greatest probability. Therefore pathologists have to identify and indicate the presence of LCD in the reports of liver needle biopsies

Biopsy, Needle↗
PubMed2000

Interleukin-10 inhibits intimal hyperplasia after angioplasty or stent implantation in hypercholesterolemic rabbits.

BACKGROUND: Intimal hyperplasia after stent implantation is the main cause of in-stent restenosis. Activated monocytes play a key role in intimal growth. The anti-inflammatory cytokine interleukin-10 (IL-10) is a potent monocyte deactivator, endogenously produced in the atherosclerotic plaque. We tested the hypothesis that exogenous IL-10 may limit postangioplasty intimal hyperplasia after balloon angioplasty or stenting. METHODS AND RESULTS: Hypercholesterolemic rabbits were treated with recombinant human IL-10 (rhuIL-10) for 3 days after balloon angioplasty or 28 days after stent implantation. High IL-10 serum levels and intense deactivation of circulating monocytic cells, assessed by inhibition of IL-1beta release by lipopolysaccharide-stimulated whole blood, were detected for at least 8 hours after rhuIL-10 intravenous injection (ELISA). Morphometric analyses, performed 28 days after injury, indicated that rhuIL-10 reduced intimal growth by approximately 50% after balloon angioplasty or stenting, resulting in more preserved lumen in stented arteries. Moreover, rhuIL-10 reduced macrophage infiltration by 67% and proliferative activity by 81% in the intima and the media. No toxic effect was detected except minor changes in blood cell count. CONCLUSIONS: The anti-inflammatory cytokine rhuIL-10 reduces postinjury intimal hyperplasia. The potent attenuation of in-stent intimal growth by rhuIL-10 and its favorable toxicity profile suggest that rhuIL-10 may be useful in the prevention of in-stent restenosis.

Animals↗
PubMed2000

Liver iron is predictive of death in alcoholic cirrhosis: a multivariate study of 229 consecutive patients with alcoholic and/or hepatitis C virus cirrhosis: a prospective follow up study.

BACKGROUND/AIMS: A study was undertaken of liver biopsy samples from 229 consecutive patients with alcoholic or hepatitis C virus related cirrhosis who were prospectively followed until January 1996 to evaluate the influence of liver iron content on survival and the occurrence of hepatocellular carcinoma. METHODS: Hepatic iron content was measured with a validated semiquantitative score, and its predictive value for survival and the occurrence of hepatocellular carcinoma was assessed. RESULTS: 130 patients had detectable iron at enrollment. During follow up (57 (28) months), 95 patients died and 39 patients developed hepatocellular carcinoma. No significant relation was found between hepatic iron and the occurrence of hepatocellular carcinoma. Conversely, the presence of iron was predictive of death in alcoholic patients (p = 0.007) by the log rank test but not in patients with hepatitis C virus related (p = 0.71) or mixed (p = 0.98) cirrhosis. The predictive value of hepatic iron content in patients with alcoholic cirrhosis was confirmed by the Cox model using either a binary coding (p = 0.009; relative risk = 2.27; 95% confidence interval 1.2 to 4.19) or the continuous values (p = 0.002). CONCLUSIONS: These results suggest that hepatic iron enhances liver lesions caused by alcohol but not those caused by hepatitis C virus.

Carcinoma, Hepatocellular↗
PubMed1999

Expert consultation for cervical carcinoma smears. Reliability of selected-field videomicroscopy.

OBJECTIVE: To evaluate the diagnostic accuracy of videomicroscopy image selection for expert consultation in cervical cytology. STUDY DESIGN: One hundred diagnostically difficult cervical cytologic smears were selected and rescreened by a general pathologist who chose, from each slide, four or five fields featuring abnormal cells. Video images were digitized and stored on a 512 x 512-pixel matrix using an image acquisition and transmission system. Five experts each reviewed 20 of the 100 cases, and a sixth reviewed all 100 cases. Diagnoses based on selected digitized images were compared to those based on conventional examination of whole slides. RESULTS: Intraobserver agreement was fair to excellent for all six experts (kappa value: 0.47-0.81); it was complete or acceptable in 68.4-85% of cases. Compared to the reference diagnosis, interobserver agreement was not significantly different whether cases were examined by screening the entire slide or by videomicroscopy of selected fields. The marked discordance in four cases concerned very small cells the significance of which was misinterpreted on videomicroscopy because of poor image quality due to lack of focus setting. CONCLUSION: This exploratory study showed that selection of videomicroscopy images seems as reliable as conventional examination of slides for expert consultation on diagnostically difficult cervical cytologic smear cases.

Adult↗
PubMed1998

Passive but not active CD8+ T cell-based immunotherapy interferes with liver tumor progression in a transgenic mouse model.

To evaluate tumor immunotherapies, we used transgenic mice that harbor a progressive liver tumor associated with the expression of the SV40 large tumor T oncoprotein (SV40-T). To induce "self" tumor Ag-specific CD8+ T cells, mice were injected with an immunodominant SV40-T CTL epitope mixed with a heterologous helper peptide. Despite repeated injections, this vaccine failed to raise a tumor-specific CD8+ T cell response that was efficient enough to counteract tumors. Although coimmunization with SV40-T CTL epitope and heterologous helper peptide efficiently recruited the respective Th cells, only low-avidity SV40-T-specific CD8+ T cells were activated. Furthermore, major alterations in SV40-T-specific B and Th cell responses were characterized. In contrast, transfers of higher-avidity CTLs specific for the same SV40-T epitope were effective in counteracting tumors. These results suggest that passive therapies targeted to self tumor Ag may be more suitable than active immunization in the treatment of spontaneous tumors.

Adoptive Transfer↗
PubMed1998

Virological and biological characteristics of cervical intraepithelial neoplasia grade I with marked koilocytotic atypia.

The aim of this study was to evaluate virologic and biological significance of marked koilocytotic atypia observed in some cases of grade I cervical intraepithelial neoplasia (CIN I). Thirty-one CIN I cervical biopsy specimens with marked koilocytotic atypia, defined by the presence of meganuclei in the superficial epithelial layers, were compared to 37 CIN I biopsy specimens with usual koilocytes for (1) the human papillomavirus (HPV) type and signal pattern as detected by nonisotopic in situ hybridization (ISH); (2) the proliferation index assessed by Ki 67 immunostaining and (3) the p53 labeling pattern. Interobserver agreement for meganuclei was excellent (k = 0.9). Twenty-five out of 68 biopsies (37%) were positive by ISH for the 6 of 11 HPV probe, 30 (44%) for the 16-18 probe, and 7 (10%) for the 31/33 HPV probe, 6 (9%) were negative for ISH. The presence of meganuclei was strongly related to high and intermediate risk HPV type (P = 0.0001). The sensitivity and specificity of meganuclei for the detection of high or intermediate risk HPV in CINI were 73 and 87%, respectively. Loss of p53 immunostaining in the lower third of the epithelium was also related to the presence of meganuclei (P < .05), but the MIB-1 index and ISH labeling pattern were not. In conclusion, marked koilocytotic atypia in CIN I is a reliable and sensitive marker for infection by high or intermediate-risk HPV, and might be a guide to therapy.

Antigens, Nuclear↗
PubMed1998

Pre-treatment with elastase improves the efficiency of percutaneous adenovirus-mediated gene transfer to the arterial media.

The endothelium and internal elastic lamina (IEL) appear to be the main barriers to adenovirus-mediated gene transfer to medial smooth muscle cells (SMC). The present randomized study tested whether controlled incubation with elastase enhanced the efficiency of catheter-based gene transfer to medial SMC by adenoviral vectors. After an initial safety dose ranging study, rabbits underwent balloon abrasion of the iliac endothelium followed by local incubation of either elastase (2 x 10(-7) IU over 5 min) or saline using a double balloon catheter (DBC). Then, adenoviral vectors (5 x 10(9) p.f.u.) carrying Cmv-Luc or RSV-beta gal reporter genes were instilled for 30 min. Three days later, the number of medial SMC expressing lacZ was increased in the elastase-treated arteries compared with saline-treated arteries (7.2 +/- 2.5 versus 2.3 +/- 0.9 cells per section, P = 0.003). Likewise, the amount of luciferase protein product was increased (70 +/- 32 versus 36 +/- 15 pg luciferase/mg tissue, P = 0.03). No vessel enlargement, light or electron microscopic evidence of injury or inflammation was seen in elastase-treated arteries up to 7 weeks. Preincubation with elastase increased transduction efficiency of catheter-based gene delivery of replication-defective adenoviral vectors to rabbit iliac arteries without detectable arterial damage.

Adenoviridae↗
PubMed1998

[Does laparoscopy reduce the incidence of useless appendectomies?].

The aim of this retrospective study is to evaluate the impact of laparoscopic appendicectomy on the incidence of histologically normal appendices. Between 1987 and 1997, 1220 consecutives patients--with an average age of 23.5 years (17-73) and including 841 women (69%)--underwent appendicectomy due to the presence of at least one of the following 3 criteria: right iliac fossa guarding, fever greater than 38 degrees C and hyperleucocytosis greater than 10,000. Patients were divided into two group.: First group with 930 patients were operated by laparotomy and the other group of 355 patients underwent laparoscopic exploration with appendicectomy when macroscopic abnormalities were observed (290 cases). In all cases, the appendices were examined under blind conditions and classified as normal or pathological, and were subsequently classified according to the nature and the severity of the lesions. In group I (laparotomy), the incidence of histologically normal appendices was 25.1%. In group II (laparoscopic), this incidence was only 8.2%. The difference was significant (p = 0.015). In 65 cases (18.3%), a macroscopically normal appendix was left in place: in 55 cases the symptoms were due to another identified cause, however, in 10 cases no cause was found. This study suggests that laparoscopy significantly reduces the number of histologically normal appendices because an other cause is identified more easily provided macroscopically normal appendices are not removed with a small proportion (5-10%) cases of early appendicitis with only mucosal involvement. In the absence of other causes for the symptoms, a three-day course of antibiotics can be tried in order to treat possible mucosal lesions. This approach reduces costs without having any adverse consequences on outcome.

Adolescent↗