Gastroprotective effects of pantoprazole against experimental mucosal damage.

The present study investigated the gastroprotective effects of the proton pump inhibitor pantoprazole on gastric mucosal damage induced by ethanol-HCl in rats. Omeprazole was used as reference drug. The morphometric analysis of gastric histological sections revealed that pantoprazole and omeprazole dose-dependently prevented the necrotic mucosal injury evoked by ethanol-HCl (ED50 = 14.1 and 21.6 micromol/kg, respectively). These effects were associated with a marked increment of Alcian blue recovery from gastric bound mucus (ED50 = 18.8 and 29.3 micromol/kg, respectively). In addition, both pantoprazole and omeprazole inhibited gastric acid secretion in pylorus-ligated rats (ED50 = 1.5 and 3.3 micromol/kg, respectively). Further experiments indicated that the protective effects of pantoprazole were not modified by L-365,260 (a gastrin receptor antagonist), suramin (a drug able to interfere with endogenous growth factors), N(G)-nitro-L-arginine (an inhibitor of nitric oxide synthase) or systemic ablation of capsaicin-sensitive sensory nerves, whereas they were partly blocked by indomethacin (an inhibitor of prostaglandin synthesis) and fully prevented by N-ethylmaleimide (a potent blocker of sulfhydryl compounds). The present data provide histomorphometric evidence that: 1) pantoprazole is endowed with gastroprotective properties and is more active than omeprazole in preventing the necrotic mucosal damage induced by ethanol-HCl; 2) according to the rank order of ED50 values, the protective effects of both drugs appear to depend mainly on the enhancement of the gastric mucosal barrier rather than on the inhibition of acid secretion; 3) an increased production of prostaglandins, as well as an increased availability of sulfhydryl radicals at the level of the gastric mucosa may account for the gastroprotective effects of pantoprazole.

Acid-independent gastroprotective effects of lansoprazole in experimental mucosal injury.

The protective effects of the proton pump inhibitor lansoprazole on gastric mucosal damage induced by ethanol-HCl or hemorrhagic shock were investigated in the present study. The morphometric analysis of gastric histological sections revealed that lansoprazole dose-dependently reduced mucosal injury evoked by ethanol-HCl (ED50 = 24.3 micromol/kg) or hemorrhagic shock (ED50 = 38.9 micromol/kg), these effects being associated with marked increments of Alcian blue recovery from gastric bound mucus (ED50 = 31.4 micromol/kg and 27.6 micromol/kg, respectively). In addition, lansoprazole inhibited gastric acid secretion from pylorus-ligated rats (ED50 = 9.8 micromol/kg). Further experiments, performed on rats with ethanol-HCl-induced gastric injury, indicated that the protective effects of lansoprazole were not modified by L-365,260, suramin, N(G)-nitro-L-arginine, or systemic ablation of capsaicin-sensitive sensory nerves, whereas they were partly blocked by indomethacin and fully prevented by N-ethyl-maleimide. In addition, lansoprazole did not modify somatostatin concentrations in gastric mucosa. The present results provide evidence that lansoprazole prevents the necrotic damage of gastric mucosa induced by ethanol-HCl or hemorrhagic shock. According to the rank order of ED50 values, these effects appear to depend mainly on the enhancement of the gastric mucus barrier rather than on the reduction of acid secretion. It is also proposed that an increased production of prostaglandins, as well as an increased availability of sulfhydryl compounds at level of gastric mucosa may account for the gastroprotective effects of lansoprazole.

Cytologic score and DNA-image analysis in the classification of borderline breast lesions: a prospective study on 47 fine-needle aspirates.

We prospectively evaluated the accuracy of the cytologic score system developed by Masood et al. combined with DNA-image analysis in the subclassification of 47 fine-needle aspiration samples with cytologic features of borderline breast lesions. Cytologic scores ranged between 12-18. All cases underwent surgical excision of the lesion, and histology revealed 24 cases of florid hyperplasia, 8 of atypical hyperplasia, and 11 noninvasive and 4 invasive ductal carcinomas. DNA-image analysis demonstrated 33 diploid and 14 aneuploid cases. Diploid samples were divided into slowly proliferating (S + G2/M < or = 13%) and rapidly proliferating (S + G2/M > 13%) cases. By considering florid hyperplasia a "low-risk" lesion and by amalgamating atypical hyperplasia, and in situ and invasive ductal carcinoma in the category of "high-risk" lesions, the positive predictive value of a score value > 16 was 100%. In cases scoring < or = 16, the slowly proliferating pattern had a negative predictive value of 95%, while the aneuploid and rapidly proliferating patterns had a positive predictive value of 100% and 63%, respectively. We conclude that a combination of cytologic score evaluation and DNA-image analysis is very useful in differentiating "low-risk" from "high-risk" cases in the field of breast borderline lesions, thus improving the impact of fine-needle aspiration diagnosis on patient management.

Gastric mucosal distribution and clinical efficacy of azithromycin in patients with Helicobacter pylori related gastritis.

The gastric mucosal distribution of azithromycin, the prototype of a new class of macrolide antibiotics named azalides, was studied in patients with duodenal ulcer and Helicobacter pylori-related gastritis. The time course of ulcer healing, H. pylori infection, and gastritis activity was also evaluated. Twenty patients (median age 50 years) received the following treatment for 1 month: three cycles of azithromycin (500 mg/day for 3 consecutive days) on days 1-3, 11-13 and 21-23 plus omeprazole (40 mg/day) for 30 consecutive days. Endoscopic biopsy specimens of gastric mucosa and blood samples were collected on days 0, 4, 7, 10, 20 and 30. An additional follow-up endoscopy was carried out on day 60. H. pylori infection was determined by both histology and rapid urease test. Azithromycin concentrations in both plasma and gastric mucosa were measured by a microbiological plate assay, using Micrococcus luteus NCTC 8440 as the reference organism. Azithromycin concentrations in plasma ranged between 0.17 mg/L (95% CI: 0.08-0.26; n = 5) and 0.32 mg/L (95% CI: 0.21-0.43; n = 5) throughout the treatment period. In addition, azithromycin concentrations in gastric mucosa were significantly higher than plasma concentrations at all times examined and ranged from 18.5 mg/kg (95% CI: 15-20; n = 20) to 24.6 mg/kg (95% CI: 16.8-32.4; n = 5), Indicating that the drug was highly retained in the target tissue. Accordingly, the ratio of azithromycin mucosal level to plasma concentration varied between 77.9 (95% CI: 56.5-99.3; n = 5) and 112.7 (95% CI: 100.2-125.2; n = 5). At the end of treatment (day 30) H. pylori was no longer detected in 16 of 20 patients (80%), and this finding was consistent with a marked decrease in the grading of gastritis activity. At the follow-up endoscopy (day 60) the infection was eradicated in only four patients (20%). These data indicate a favourable distribution of azithromycin into gastric mucosa of patients with H. pylori infection and suggest that this new macrolide antibiotic represents a valuable option for treatment regimens against H. pylori. However, the low eradication rate achieved with azithromycin plus omeprazole is a source of concern and requires further investigation.

Suramin enhances ethanol-induced injury to gastric mucosa in rats.

Suramin is currently used in clinical practice as antineoplastic agent because of its complex interaction with the biological activity of various growth factors involved in tumor progression. The influence exerted by suramin on gastric injury induced in rats by intraluminal injection of absolute ethanol was investigated in the present study. The morphometric analysis of gastric histological sections revealed that suramin, 18 mg/kg, administered intraperitoneally for 14 days every other day, caused a marked enhancement of ethanol-induced mucosal damage. This effect was more pronounced 1-8 hr following ethanol administration, and it was still significant after 48 hr. In suramin-treated animals the evaluation of Alcian blue recovery from gastric-bound mucus showed that the levels of adherent mucus were significantly lower than those detected in untreated rats. In addition, pretreatment with suramin did not modify basal acid secretion, but caused potentiation of acid output stimulated by pylorus ligation or electrical vagal stimulation. Overall, the present results indicate that suramin exerts a negative influence on both gastric protective and repairing mechanisms. Due to the peculiar pharmacodynamic profile of suramin, it is suggested that interference with endogenous growth factors, endowed with physiological protective activity on gastric mucosa, might account for the damage-enhancing action of this drug.

Neuroendocrine carcinoma of the thymus: aspiration biopsy, immunocytochemistry, and clinicopathologic correlates.

We report three cases of well-differentiated neuroendocrine carcinoma originating primarily in the anterior mediastinum which had been initially investigated by fine-needle aspiration cytology in conjunction with immunocytochemistry and subsequently recognized as thymic in origin. Aspirates consisted of loosely cohesive or aggregated medium sized elements with round to oval nuclei and scanty cytoplasm. In all cases the Romanowsky stain provided an excellent delineation of definite paranuclear inclusion-like structures having a semicircular or discoid appearance which appeared to contain cytokeratin by immunocytochemical studies and were very similar to the intermediate filament paranuclear "buttons" found in neuroendocrine Merkel cell carcinoma of the skin. This appears to be a novel cytologic observation for thymic neuroendocrine carcinoma. We discuss the significance of the above cytologic and immunocytochemical findings and their possible role in the diagnosis of thymic neuroendocrine carcinoma by fine-needle aspiration biopsy.

Mechanisms of protection by omeprazole against experimental gastric mucosal damage in rats.

In the present study, the protective effect of omeprazole on gastric mucosa injury induced by ethanol.HCl in rats and the putative mechanisms involved in this action were investigated. Misoprostol and ranitidine were used as reference drugs. The morphometric analysis of histological sections showed that omeprazole caused a significant reduction of mucosal necrotic damage, this effect being associated with a marked increase in Alcian blue recovery from gastric bound mucus. In addition, omeprazole elicited a significant inhibition of gastric acid secretion from pylorus-ligated rats. Misoprostol exerted similar effects to those obtained with omeprazole, even if the Alcian blue recovery and the acid output were affected to a lesser extent. By contrast, ranitidine failed to influence both the mucosal damage and the Alcian blue recovery, while it exerted a marked inhibition on acid secretion. The present results indicate that omeprazole is effective in protecting gastric mucosa from necrotic damage induced by ethanol.HCl and suggest that an enhancement of gastric mucus barrier may account for this protective action.

Protective action of omeprazole against gastric mucosal injury induced by hemorrhagic shock in rats.

The efficacy of omeprazole in preventing gastric mucosal injury induced by hemorrhagic shock in rats and the putative mechanisms involved in this effect were investigated in the present study. Omeprazole did not affect mean arterial blood pressure under both basal conditions and induction of hemorrhagic shock, but it evoked a marked increase in Alcian blue recovery from gastric preepithelial mucus. The morphometric analysis of histological sections revealed that omeprazole caused a significant reduction of hemorrhagic shock-induced damage of gastric mucosa. Ranitidine, used as the reference drug, failed to affect mean arterial blood pressure, Alcian blue recovery from gastric mucus, or hemorrhagic shock-induced damage of gastric mucosa. Both omeprazole and ranitidine exerted a significant inhibition of gastric acid output from anesthetized pylorus-ligated rats. Overall, the present results indicate that omeprazole is effective in protecting gastric mucosa from necrotic damage induced by hemorrhagic shock and suggest that an enhancement of gastric mucus secretion contributes to this protective action.

Decisive role of immunocytochemistry in aspiration cytology of chordoma of the clivus: a case report with review of the literature.

Immunocytochemistry (ICC) proved to be an essential adjunct in the fine-needle aspiration (FNA) cytological diagnosis of chordoma of the clivus in a 62-year-old woman. The cytological picture in routinely stained smears was not entirely diagnostic for chordoma due to the paucity of typical 'physalipherous' cells. To exclude other primary or metastatic neoplasms of the skull base possibly sharing the same cytological picture, additional direct smears were immunostained with antibodies specific for cytokeratin (CK), vimentin (VIM), S100 protein (S100P), carcinoembrionic antigen (CEA), epithelial membrane antigen (EMA), glial fibrillary acidic protein (GFAP), CD68 antigen (KP1) and with the 'panepithelial' antibodies B72.3 and Ber-EP4. Chordoma cells showed the following immunoprofile: CK+/VIM+/S100P+/CEA-/EMA+/GFAP-/B72.3-/Ber-EP4-/CD68+. The pattern of immunoreactivity for CK, S100P and CEA confirms previously reported data, while the B72.3-/Ber-EP4-/CD68+ staining profile represents a novel observation. The detection of a CK+/S100+/CEA-/B72.3-/Ber-EP4- immunocytological profile of chordoma cells in aspirates is a basic requirement to exclude pertinent diagnostic differentials, such as metastatic carcinoma, ependymoma and sarcoma, and permits a reliable pre-operative diagnosis of the tumour by aspiration cytology.

Microglandular adenosis of the breast: fine-needle aspiration biopsy of two cases.

Microglandular adenosis (MGA) recognizes a benign proliferative lesion of the breast that can mimic adenocarcinoma histologically. We describe the fine-needle aspiration (FNA) biopsy cytology of MGA in two female patients. Smears were characterized by sparse cellularity, and the harvest consisted of a monotonous population of medium-sized cells, with vacuolated clear cytoplasm and round and uniform nuclei with small nucleoli. Clear cells appeared isolated or clustered with spindly fibroblasts. No naked nuclei of myoepithelial origin were present in the background. The differential diagnostic considerations included several breast lesions composed of clear cells. Subsequent surgical histology of lumpectomy revealed MGA. Further studies are needed to determine whether these cytologic features permit the specific identification of MGA, but our observations show that FNA is a sensitive method in recognizing the benign nature of the lesion.

Immunocytochemistry in head and neck aspirates. Diagnostic application on direct smears in 16 problematic cases.

This report describes our experience with immunocytochemical staining of routinely processed smears in the fine needle aspiration (FNA) biopsy diagnosis of 16 tumors of the head and neck. Immunocytochemistry (ICC) was performed on alcohol-fixed or air-dried smears using commercially available monoclonal antibodies followed by a streptavidin-biotinylated peroxidase labeling method. In 12 aspirates with cytologically unclassifiable and undifferentiated cells, immunostaining for cytokeratin, leukocyte common antigen, S-100 protein and vimentin provided conclusive evidence of cell lineage. ICC permitted the correct identification and differential diagnosis of four additional tumors: a positive immunoreaction for thyroglobulin identified a metastatic Hürthle cell carcinoma of the thyroid; a coexpression of two distinct classes of intermediate filaments helped support the FNA diagnoses of a parathyroid adenoma and of a synovial sarcoma; and the double immunoreaction for CD15 and CD30 antigens helped identify Reed-Sternberg cells within an unusually suppurative harvest. Two immunostains were required for proper diagnosis in 13 cases and four in the remaining 3. In all cases but one only unstained slides were used. These data demonstrate that immunostaining can conveniently and advantageously be performed on direct smears of aspirated samples of head and neck lesions, but cases should be carefully selected for this procedure.

Parotid metastasis of Merkel cell carcinoma in a young patient with ectodermal dysplasia. Diagnosis by fine needle aspiration cytology and immunocytochemistry.

Fine needle aspiration (FNA) biopsy was performed on an intraparotid lymph node metastasis of a Merkel cell carcinoma of the eyelid in a 15-year-old girl with antecedent ectodermal dysplasia syndrome. The cytologic appearance of the aspirate and the results of immunocytochemical typing of intermediate filaments on the FNA smears provided a definitive diagnosis. The Romanowsky stain provided an excellent delineation of paranuclear intracytoplasmic "buttons," which appeared to contain both cytokeratin and neurofilaments by immunocytochemical studies. These findings confirm previous data emphasizing the role of light microscopic observations, supplemented by proper immunocytochemical investigations, in the differential diagnosis of metastatic Merkel cell carcinoma in fine needle aspirates.