Oxidative stress in gastric mucosa of asymptomatic humans infected with Helicobacter pylori: effect of bacterial eradication.

BACKGROUND: Inducible nitric oxide synthase (iNOS) and interleukin 8 (IL-8) are positive in approximately 50% of Helicobacter pylori-related diseases but it is not clear whether oxidative stress is also present in H. pylori asymptomatic humans. Our aim was to study the expression of iNOS, superoxide dismutase, catalase and IL-8 production in H. pylori-infected asymptomatic humans, and to investigate the effect of eradication of H. pylori. MATERIALS AND METHODS: Biopsies of corpus and antrum of asymptomatic H. pylori positive and negative humans served for determination of the gastritis score and H. pylori status; iNOS was measured by reverse transcriptase polymerase chain reaction and immunohistochemistry and superoxide dismutase and catalase by immunohistochemistry. IL-8 in biopsies was assessed by enzyme-linked immunosorbent assay. RESULTS: Immunostaining of iNOS, catalase and superoxide dismutase was significantly associated with H. pylori infection and was localized to inflammatory cells. IL-8 concentrations were greater in the H. pylori positive than H. pylori negative group and decreased after bacterial eradication. A decrease in staining for iNOS and catalase was observed after H. pylori eradication. CONCLUSIONS: INOS and antioxidant enzymes are present in gastric biopsies of asymptomatic H. pylori positive humans. Eradication caused a significant decrease in staining for iNOS and catalase. These results indicate that oxidative stress occurs in asymptomatic patients and can be modulated by H. pylori eradication.

Helicobacter pylori eradication attenuates oxidative stress in human gastric mucosa.

OBJECTIVE: Helicobacter pylori infection causes gastric diseases, but the responsible mechanisms are not completely understood. They can involve DNA and tissue damage induced by reactive oxygen and nitrogen species. Our aim is to investigate the effects of bacterial eradication on oxidative stress by measuring changes of relevant markers. METHODS: Antral biopsies were obtained from 34 patients with chronic atrophic gastritis and peptic ulcer disease before and after bacterial eradication. The expression of inducible nitric oxide synthase (iNOS) and levels of nitrotyrosine (NTYR) and 8-hydroxy-2'-deoxyguanosine were assessed immunohistochemically as markers of nitric oxide (NO) production and of damage to proteins and DNA, respectively. RESULTS: Before treatment, the percentages of patients with staining were: 56 for iNOS in inflammatory cells, 79 and 61 for NTYR and 8-hydroxy-2'-deoxyguanosine in foveolar cells, respectively, and 82 for 8-hydroxy-2'-deoxyguanosine in lymphoid follicles. NTYR staining was associated with the intensity of inflammation (p = 0.04) and gastritis activity (p = 0.07). The prevalence of 8-hydroxy-2'-deoxyguanosine tended to be associated with that of NTYR. After successful H. pylori eradication, the prevalence of iNOS and NTYR (in mild gastritis) staining decreased (p < 0.001 and p < 0.06, respectively). 8-Hydroxy-2'-deoxyguanosine staining disappeared in 24% of cases but appeared in 18% of previously negative cases despite eradication. CONCLUSION: Targets of oxidative stress associated with H. pylori infection are inflammatory and deep foveolar cells and lymphoid follicles. This is the first report of 8-hydroxy-2'-deoxyguanosine localization in gastric mucosa. Oxidative stress is reduced by bacterial eradication in the first stages of mild gastritis. Moderate-severe gastritis may be a step that is reversible for iNOS, but partly irreversible for NTYR and 8-hydroxy-2'-deoxyguanosine.

[Progressive limb lengthening with a centromedullary nail versus an external fixator: experimental study in sheep]. / L'allongement progressif des membres par clou mécanique centro-médullaire d'allongement: étude expérimentale chez le mouton.

PURPOSE OF THE STUDY: Progressive limb lengthening with an external fixator often leads to pin-related complications. A new technique allowing progressive lengthening with a centromedullary nail without external fixation has been developed. This original double-locked device consists of matching male and female components fitted with a continuous thread. Lengthening is achieved via a one-way ratchet system. Twelve back-and-forth movements produce 1.25 mm lengthening. MATERIAL AND METHODS: We tested this new device on 20 sheep and compared results with external fixation lengthening in 20 other sheep. The animals were divided into groups for sacrifice on days 5, 10, 20, 45 and 90. Serial x-ray were obtained for all animals. In the 45-day and 90-day groups, histomorphometric (trichrome goldner coloration and polarized light microscopy) and densitometric studies were also performed. Bone mineral density (BMD) was determined and bone trabecular density (BTD) and trabecular bone volume (TBV) were expressed in percent of bone trabecular surface area. RESULTS: Mean lengthening in the 45-day and 90-day groups was 39 mm for the nail and 20 mm for external fixation (1 mm/day). At 90 days, 3 sheep out of 4 had consolidated radiologically with external fixation and 2 out of 4 with the nail. BMD was slightly better for external fixation (0.811 vs 0.695/cm(2)). This difference could probably be attributed to the greater lengthening obtained with the nail. At 45 days, BMD was the same (0.6 g/cm(2)) for both devices. BTD was nearly two-fold higher for the nail compared with external fixation (59.65% vs 32.61% at 90 days), most probably due to primary bone formation. The histomorphometric study allowed an analysis of the osteoid border. Bone quality obtained in the bone regenerate with the nail was superior to that obtained with external fixation. Primary bone formation resulted from membrane ossification with direct transformation of fibroblasts into osteoblasts. CONCLUSION: This work demonstrated that progressive lengthening can be achieved with a specifically designed centromedullary nail without iterative opening of the operative site. Tolerance to this type of device and quality of the bone regenerate are altogether satisfactory.

[Primary pulmonary synovial sarcoma. Apropos of 1 case with cytogenetic study]. / Synovialosarcome pulmonaire primitif. A propos d'un cas avec étude cytogénétique.

Synovial sarcoma most commonly occurs in the peri-articular regions of the extremities. We report a case of primary pulmonary monophasic synovial sarcoma. This tumor is extremely rare and shows a particular immunohistochemical pattern of great help for the diagnosis. Cytogenetic study confirm the diagnosis by showing the specific t (X; 18) chromosomal translocation, characteristic of synovial sarcoma in all anatomic locations.

Effects of proton beam irradiation on uveal melanomas: a comparative study of Ki-67 expression in irradiated versus non-irradiated melanomas.

AIMS: To assess the cellular proliferation using the monoclonal antibody Ki-67, in paraffin embedded uveal melanomas irradiated by proton beam, as well as in non-irradiated uveal melanomas. METHODS: 30 enucleated eyes were included for histopathological study and Ki-67 immunostaining. Patients were enucleated between 1991 and 1996 for uveal melanoma, 14 after proton beam irradiation and 16 without treatment (control group). The mean follow up period was 2.5 years after diagnosis and 1 year after enucleation. RESULTS: A significant relation was found between Ki-67 score and mitotic index (r = 0.56, p = 0.001), histological largest tumour diameter (r = 0.38, p = 0. 03), fibrosis (r = -0.35, p = 0.05), absence of tumoral pigmentation (p = 0.05), and presence of vascular thrombosis (p = 0.03). The Ki-67 score was significantly higher in the non-irradiated group (p = 0.01) and in the group of patients whose cause of enucleation was tumoral evolution (p = 0.005) compared with the group of patients enucleated after neovascular glaucoma. The Ki-67 score was very high in a case of orbital recurrence of uveal melanoma and metastatic death. 70% of metastasised tumours showed a Ki-67 score higher than the median value. CONCLUSION: Ki-67 labelling is a reliable method of estimating the proliferative activity in uveal melanomas after proton beam irradiation. The Ki-67 score is significantly correlated with prognostic variables (mitotic index and histological largest tumour diameter), and with radiation effects after proton beam irradiation.

[Standards, options and recommendations (SOR) for diagnosis, treatment and follow-up of osteosarcoma. Groupe de travail SOR]. / Standard, Options et recommandations (SOR) pour le diagnostic, le traitement et la surveillance de l'ostéosarcome.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. For pediatric issues, this project is a collaboration between the FNCLCC and the French Society of Pediatric Oncology (SFOP). The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of Standards, Options and Recommendations for the clinical care of osteosarcoma in children and adult. METHODS: Data have been identified by literature search using Medline (1985-december 1998) and the expert groups personal reference lists. The main criteria considered were incidence, risk factors, prognostic factors and efficacy of treatment. Once the guidelines were defined, the document was submitted for review to 27 national and international independent reviewers, and to the medical committees of the 20 French Cancer Centres and, in particular, the 4 which have particular expertise in pediatric cancer management. RESULTS: The main recommendations for osteosarcoma management are that: 1) the clinical diagnosis is based on appropriate clinical and radiological findings; 2) the final diagnosis is pathological and the biopsy should be performed by the surgeon who will subsequently perform the definitive surgery; 3) surgical biopsy must be of adequate size and performed by an experienced surgeon; 4) the therapeutic strategy for osteosarcoma is based on surgery with neoadjuvant and adjuvant chemotherapy given in experienced centres. Inclusion of high dose methotrexate is recommended for children, and the dose of methotrexate must be adapted for adults. Inclusion of children in SFOP protocols and adults in EORTC and FNCLCC clinical trials is recommended; 5) treatment of metastatic osteosarcoma is based on chemotherapy and surgery to lung metastases which may be curative. Amputation is rarely appropriate. Inclusion of children in SFOP and of adult in EORTC and FNCLCC clinical trials for metastatic osteosarcoma is recommended; 6) at the present time, there are no clear data on which to base guidelines for timing and duration of follow-up studies in this condition.

Cytological aspiration of intraocular retinoblastoma in an 11-year-old boy.

Only a few cases of retinoblastomas in older children have been reported and the clinical diagnosis may be difficult. In case, fine-needle aspiration from an atypical retinal mass of an 11-yr-old boy was performed. The vitreous fluid was stained with Diff-Quik for an immediate cytological examination and the diagnosis of retinoblastoma was suggested. The rest of the specimen was separated into two parts. One was stained with May-Grünwald-Giemsa and the other was centrifuged, embedded in paraffin, and finally stained with hematoxylin-eosin-safran. The undifferentiated blue cells were associated with abundant necrotic debris and portions of capillaries with perivascular tumor cells around. The cytoplasm of the tumor cells was strongly stained with neuron-specific enolase antibody. The diagnosis of retinoblastoma was confirmed. The specimen of enucleation confirmed the diagnosis. In conclusion, cytological aspiration can categorically diagnose suspected intraocular tumors of older children in whom clinical and noninvasive investigations have failed to establish the diagnosis.

[Sarcoma of the pulmonary artery]. / Sarcomes de l'artére pulmonaire.

Two cases of pulmonary artery angiosarcomas are reported. Pulmonary artery tumor was diagnosed during exploratory thoracotomy in the first case. It was suspected on magnetic resonance imaging and confirmed by surgery in the second case. The therapeutic was a right pneumonectomy for the first patient and a tumor resection followed by chemotherapy and radiotherapy on cerebral metastases for the second patient. Both our patients died, 13 and 44 months after surgery. On the basis of histological and immunohistochemical findings both tumors were angiosarcomas. Ultrastructural examination in the second case revealed an endothelial differentiation. The review of 142 previously reported cases of pulmonary artery sarcomas and these ultrastructural findings suggest that pulmonary artery sarcomas may have multiple origins; leiomyosarcomas deriving from arterial smooth muscle; angiosarcomas deriving from the endothelium and undifferentiated sarcomas or "myointimal sarcomas" deriving from myointimal cells.

Fine needle aspiration cytology of a solid papillary carcinoma of the breast. A case report with immunohistochemical studies.

BACKGROUND: Solid papillary carcinoma of the breast was recently described. This tumor display distinctive clinical and morphologic features. It is an intraductal papillary carcinoma frequently associated with mucinous carcinoma and infiltrating ductal carcinoma not otherwise specified. CASE: Fine needle aspiration cytology (FNAC) of a solid papillary carcinoma of the right breast in an 82-year-old female, demonstrated a cellular specimen of discohesive, small, uniform and ovoid tumor cells, with occasional loose cluster. The cytoplasm was abundant and finely granular. The nuclei were round, without marked atypia. The nucleoli were inconspicuous. SCant mucinous material was present. The diagnosis was confirmed histologically and immunohistochemically. CONCLUSION: The cytologic aspects of solid papillary carcinoma of the breast suggest a carcinoma with endocrine differentiation and a weak mucinous component.

Inducible nitric oxide synthase, anti-oxidant enzymes and Helicobacter pylori infection in gastritis and gastric precancerous lesions in humans.

Chronic inflammation induced by Helicobacter pylori infection has been associated with an increased risk of stomach cancer. We have analysed 167 stomach biopsies from 99 patients for H. pylori infection and immunohistochemically for the expression of inducible nitric oxide synthase (iNOS), catalase and superoxide dismutases (SODs) as markers of oxidative stress. Biopsies were graded as follows on the basis of histology: normal, superficial gastritis, variable severity of atrophic gastritis with or without intestinal metaplasia, and dysplasia. iNOS was detected in inflammatory cells in all types of gastritis with or without H. pylori infection and independently of its severity. In foveolar cells, iNOS was observed in approximately 25% of all biopsies showing any type of gastritis, but in a markedly higher proportion of dysplastic samples. Catalase and Mn-type SOD in inflammatory cells and catalase in foveolar cells were more frequently observed in marked atrophic gastritis biopsies than in less severe gastritis. Individual differences were found in the expression of these enzymes within groups with the same severity of gastritis. Prolonged oxidative stress in severe gastritis and dysplasia may play an important role in gastric carcinogenesis, through increased damage of DNA and tissue by reactive oxygen and nitrogen species.

[Histopathologic study of melanoma of the choroid after proton therapy]. / Etude histopathologique des mélanomes choroïdens après protonthérapie.

To evaluate irradiation effects on choroidal melanomas, histopathologic findings of 18 eyes whose primary treatment was enucleation were compared to 15 eyes enucleated after proton beam irradiation. Irradiated tumors showed more likely necrosis (p = 0.01) had balloon cells (p = 0.01), and inflammatory infiltrate (p = 0.05). In the irradiated group, the prevalence of tumor blood vessel damage was higher (p = 0.0002) and mitotic figures were fewer (p = 0.01). These findings suggest that proton beam irradiation damages tumor cells and alters the tumor's capacity for cellular reproduction. It damages blood vessels leading to tumor necrosis. It induces an inflammatory response of unknown effects. Radiosensitivity of choroidal melanomas cannot be assessed using conventional histologic methods. However, tumor necrosis, mitotic activity and rate of balloon cells can help to establish tumoral sensitivity to irradiation.

[Glomangioma: an unusual ethmoid-nasal tumor]. / Glomangiome: une tumeur ethmoïdo-nasale inhabituelle.

Glomus tumors are benign vascular tumors usually located in the fingertip dermis. Extracutaneous glomus tumors are extremely rare. A new case of sino-nasal glomangioma is reported and both clinical and histological features and biological behavior of glomus tumors in this exceptional site are described.

Loss of heterozygosity of the RB gene is a poor prognostic factor in patients with osteosarcoma.

PURPOSE: The usual therapy of osteosarcoma is neoadjuvant chemotherapy, followed by surgery, then by postoperative chemotherapy. There is no prognostic factor to predict, at diagnosis, the histologic response and final outcome. Inactivation of the retinoblastoma-susceptibility gene RB is associated with the pathogenesis of several human cancers. In primary osteosarcomas, loss of heterozygosity (LOH) at the RB locus has been found in greater than 60% of cases. The aim of this study was to determine the potential early prognostic value of LOH of RB gene on the biopsy material at diagnosis. PATIENTS AND METHODS: Forty-seven patients with primary osteosarcoma, treated in four French institutions, were studied. LOH was studied by polymerase chain reaction (PCR) of an informative RB DNA polymorphism. RESULTS: Assessment of LOH at the RB gene could be completed on 34 heterozygous patients only. LOH was found in 24 cases (70%). The event-free survival (EFS) rate at 60 months is 100% for patients without LOH, 43% for all patients with RB LOH, and 65% for nonmetastatic patients with RB LOH. The difference in EFS is highly significant at P = .008 and P = .024, respectively. Histologic response after preoperative chemotherapy did not show significant correlation with LOH status. CONCLUSION: RB gene LOH appears to be an early predictive feature for osteosarcomas that indicates a potential unfavorable outcome. RB LOH study might shortly help to identify high-risk patients earlier. If this is verified, therapy could then be adapted earlier to the individual's real risk of relapse.

Crescentic glomerulonephritis and crystals within glomerular capillaries in an AIDS patient treated with foscarnet.

We report on a 28-year-old AIDS patient who developed a rapidly progressive glomerulonephritis while being treated with foscarnet for cytomegalovirus retinitis. Renal biopsy showed crescentic proliferation related to crystals within the glomerular capillaries. The role of foscarnet in this unusual renal syndrome is discussed.

[Hepatic epithelioid hemangioendothelioma. A case with liver transplantation. Review of the literature]. / Hémangioendothéliome épithélioïde hépatique. Un cas avec transplantation hépatique. Revue de la littérature.

Epithelioid hemangioendothelioma (HEE) is an unusual malignant neoplasm of vasculo-endothelial origin, arising in soft tissues, lung and liver. One case of hepatic HEE is reported in a 32 year-old man wit an isolated multinodular hepatomegaly. The diagnosis was made by the histologic examination of biopsy specimens. At the time of diagnosis, there was evidence of pulmonary metastasis. However, an orthotopic liver transplantation was performed. The tumor cells were immunoreactive with factor VIII-related antigen, BNH9 and vimentin. There was no expression of cytokeratin and epithelial membrane antigen. The patient is alive and well 24 months after. The thoracic X-ray are unchanged. This case is compared with the 84 others cases of the literature. Fourteen experienced a favorable outcome after transplantation. Extra-hepatic dissemination doesn't contra-indicate the graft. But hilar vascular involvement may be correlated with worse prognosis.

[Primary bone lymphoma disclosed by osteolytic lesion of the femoral head]. / Lymphome osseux primitif révélé par une lésion ostéolytique de la tête fémorale.

A case of primary lymphoma of the bone is reported. The unusual site of the tumor in an epiphysis (head of femur) led to unconventional therapy by resection and hip replacement. Emphasis is put on the value of immunolabelling studies for the etiologic diagnosis.

Human papillomavirus DNA in cervix. In-situ hybridization with biotinylated probes on Bouin's fixed paraffin embedded specimens.

We examined retrospectively a series of 65 Bouin's fixed, paraffin-embedded tissue specimens from 8 condylomatous lesions, 16 condylomas associated with cervical intraepithelial neoplasia (CIN), and 12 neoplasia without condylomatous signs, for histological characteristics, the detection of viral structural antigen, the presence and typing of HPV DNA by molecular in situ hybridization with biotinylated probes types 6, 11, 16 and 18 under stringent conditions (Tm - 12 degrees C). HPV DNA was present in 34/65 (52%) specimens. Detection of viral structural antigen was positive in only 14% (3/22) specimens. HPV DNA were identified in 9/9 (100%) condylomatous lesions (with HPV type 6, 11, 18). Three condylomas were coinfected with both HPV type 6 or 11 and type 18; viral antigen was found in two specimens. HPV DNA were detected in 18/31 (58%) low grade and advanced CIN associated with condylomatous changes (type 6 = 5 specimens, type 11 = 3 specimens, type 16 = 4 specimens, type 18 = 6 specimens). Four of these cases were coinfected with both HPV type 6/11 and HPV type 16/18. Viral antigen was negative in all specimens. HPV DNA were detected in 7/25 (28%) advanced intra-cervical neoplasia (CIN III) without anatomopathological condylomatous changes (type 6 = 1 specimen, type 16 = 3 specimens, type 18 = 3 specimens). One of these specimens contained both HPV types 6 and 18. Viral antigen was found in one case. Our data confirm the association of HPV types 6 and 11 with condyloma and low grade neoplasia; HPV types 16 and 18 were associated with advanced cervical neoplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Study of an inhibitor of plasminogen activator (tranexamic acid) in the treatment of experimental osteoarthritis.

The effects of tranexamic acid, an inhibitor of plasminogen activator, were evaluated in a rabbit model of osteoarthritis induced by section of the knee joint anterior cruciate ligament. Prophylactic treatment administered intramuscularly thrice weekly for 12 or 24 weeks significantly reduced cartilage destructive lesions, increased cartilage hypertrophy but did not prevent changes in cartilage water and proteoglycan content. A suppression of synovial membrane stromelysin and collagenase activity was found while phospholipase A2 activity was unaffected.