Prognostic and diagnostic implications of MMP-2, MMP-9, and VEGF-α expressions in colorectal cancer.

PURPOSE: Angiogenesis and tumor invasion are complex processes that are mediated by various proteins, such as vascular endothelial growth factor (VEGF-α) and the matrix-degrading enzymes metalloproteinase-2 and -9 (MMP-2, MMP-9). The aim of this study was to determine what roles MMP-2, MMP-9, and VEGF-α play in colorectal cancer (CRC) by correlating their expression levels with the cancer TNM stage, modified Dukes criteria, degree of cell differentiation, and long-term patient survival. METHODS: The present series consisted of tissue samples obtained from 180 patients who had undergone large bowel resection during 1995 and 2005 at the Luis Antonio Hospital. Archival paraffin-embedded CRC tissue samples were used to generate tissue microarray blocks, which were immunohistochemically stained for MMP-2, MMP-9, and VEGF-α. Three different grading systems were applied to evaluate staining intensity. Chi-squared Person test and Kaplan-Meier survival curves were used, and values of p<0.05 were considered statistically significant. RESULTS: MMP-2 expression showed a significant association with more invasive cancer stages (p<0.001) and death (p<0.041). VEGF-α expression correlated with a high TNM stage (p<0.009), the degree of cell differentiation (p<0.025) and patient death as a result of disease (p<0.035). The Kaplan-Meier survival estimated that patients with strong staining for MMP-2 (log-rank x(2)=34.09; p<0.0001), MMP-9 (log-rank x(2)=12.83; p<0.0003) and VEGF (log-rank x(2)=33.9; p<0.0001) showed a greater tendency towards death during 60 months of follow up. CONCLUSIONS: The quantification of VEGF-α, MMP-2 and MMP-9 expression in colorectal cancer may be related to survival. These data add to the growing epidemiological and experimental evidence that VEGF-α, MMP-2 and MMP-9 may play a role in colorectal tumorigenesis.

Detection and expression of bovine papillomavirus in blood of healthy and papillomatosis-affected cattle.

Papillomaviruses (PV) are double-stranded DNA viruses that can cause benignant and malignant tumors in amniotes. There are 13 types of bovine papillomavirus (BPV-1 to -13); they have been found in reproductive tissues and body fluids. Normally these viruses are detected in epithelial tissue. We looked for BPV in the blood of healthy cattle and cattle with papillomatosis, using PCR and RT-PCR. BPV types 1 and 2 were detected in 8/12 blood samples of asymptomatic bovines and in 8/9 samples from cattle with papillomatosis. Six of 8 asymptomatic samples positive for BPV also showed expression for BPV. Five of 6 samples were positive for E2 expression, while 3/6 samples were positive for E5 expression. Five of 8 symptomatic samples positive for BPV also showed BPV expression. Five of 5 were positive for E2 expression, while 1/5 was positive for E5 expression. Two of 6 blood samples of asymptomatic cattle and 1/5 symptomatic blood samples scored positive for both E2 and E5 expression. This is the first study showing expression of BPV genes in the blood of asymptomatic and papillomatosis-affected animals.

Expression of the bovine papillomavirus type 1, 2 and 4 L1 genes in the yeast Pichia pastoris.

Papillomaviruses are known to cause benign or malignant lesions in various animals. In cattle, bovine papillomavirus (BPV) is the etiologic agent of papillomatosis and neoplasia of the upper gastrointestinal tract and urinary bladder. Currently, there are no standard diagnostic tests or prophylactic vaccines. Protection against papillomavirus infection is conferred by neutralizing antibodies directed towards the major structural protein L1. These antibodies can be efficiently induced by immunization with virus-like particles that are formed spontaneously after L1 gene expression in recombinant systems. The yeast Pichia pastoris is known to provide an efficient system for expression of proteins due to reduced cost and high levels of protein production. We evaluated P. pastoris for expression of the L1 gene from BPV1, BPV2 and BPV4. After methanol induction, the recombinants were able to produce L1 proteins of the three different BPV types. To increase heterologous L1 protein levels, a codon optimization strategy was used for production under bioreactor conditions. The BPV1 L1 protein was identified by monoclonal antibody anti-6xHis. This is the first report of BPV L1 expression in yeast.

Endosonographic Doppler-guided manometry of esophageal varices: experimental validation and clinical feasibility.

BACKGROUND AND STUDY AIMS: The risk of variceal bleeding cannot be accurately predicted using endoscopy alone. Although variceal pressure has been demonstrated to be a major determinant for the rupture of esophageal varices, direct determination by needle puncture is unsuitable for routine clinical use. Due to their operator-dependency, current noninvasive endoscopic methods for determination of variceal pressure have not gained wide acceptance. We have developed a new method of measuring variceal pressure, using endoscopic power Doppler imaging to monitor the manometry of esophageal varices. The aims of this study were to test in vitro the accuracy of Doppler-guided manometry and to assess the clinical feasibility of this method. MATERIALS AND METHODS: Experimental validation of this technique was performed using an in vitro model of artificial varices of different sizes. A linear-array endosonography (EUS) probe with power Doppler capability was used to assess flow in the varices and a balloon for manometry of esophageal varices was attached to the tip of the probe. Pressure readings were made at the time of disappearance of the Doppler signal during variceal compression by the balloon. Linear regression analysis was used to compare the results of Doppler-guided and direct intraluminal pressure measurement in the artificial varices. Variceal pressure was then measured with this technique in 28 patients with portal hypertension and esophageal varices without previous bleeding, and the results were compared with portal pressure assessed according to the hepatic vein pressure gradient (HVPG). RESULTS: In vitro studies demonstrated a good correlation between the pressure measured with Doppler monitoring and the actual intravariceal pressure (r > or = 0.922; P < 0.001). The determination of variceal pressure with this method was technically successful in 26/28 patients (93 %). The intraoperator variance was 9.3 +/- 8.6 %. Overall, the mean variceal pressure was significantly lower than the mean HVPG (21.2 +/- 5.3 mmHg vs. 24.3 +/- 7.8 mmHg; P < 0.01). Variceal pressure and portal pressure (as assessed by the HVPG) correlated significantly (r = 0.64; P < 0.001). CONCLUSIONS: Our preliminary results indicate that EUS Doppler-guided manometry of esophageal varices is feasible and accurate. This technique may become a more reliable method for noninvasive measurement of variceal pressure and warrants further investigation.

[Secondary biliary cirrhosis in a patient with histiocytosis X]. / Cirrose biliar secundária em doente com histiocitose X.

Histiocitose X or Histiocytosis of the Langerhans cells represents a complex spectrum of clinical alterations, resulting from infiltration by anomalous histiocytes of various organs, including the skin, bones, lungs, lymphatic ganglia and liver. Liver disease is rare and the mechanism by which lesions appear is unknown. Cholestasis results from phenomena of sclerosant colangitis, which affects the intrahepatic ducts, or from proliferation of histiocytic cells in the periportal areas. Some patients develop biliar cyrrhosis. The authors present the clinical case of a 62-year-old female patient, hospitalized for chronic cholestasis, diabetes and gallstone in the main bile duct. She had metastatic lesions of the hypophysis and bones, the biopsies of which revealed infiltration by histiocytic cells. Endoscopic Retrograde Colangiopancreatography (E.R.C.P.) revealed dilatation of intrahepatic bile ducts and stenosis of left hepatic duct. A histological study of the hepatic biopsy showed chronic cholestasis and areas of fibrosis, without infiltration by histiocytic granulomas, which were observed in the medular biopsy and in the thyroid nodule cytology.

Biogenic amines occurrence in wine. Amino acid decarboxylase and proteolytic activities expression by Oenococcus oeni.

This work deals with the study of the proteolytic and amino acid decarboxylase activities of selected Oenococcus oeni isolates and the effect of yeast autolysis on biogenic amines production in wine. A total of 220 isolates of O. oeni were tested for decarboxylase and proteolytic activity. Only six isolates showed both activities, but only after a period of adaptation in a growth medium containing wine. The results reported on this paper show that proteolytic activity was dependent on medium composition and bacterial growth phase. It can be assumed that the ability of O. oeni to use wine peptides and to produce biogenic amines is not a constant characteristic of this species, and enzymatic system expression appears to be closely dependent on nutritional and energetical composition of the medium. It also seems to be strain dependent and not widespread among this bacterial community.

Endosonography in the diagnosis of "blue rubber bleb nevus syndrome": an uncommon cause of gastrointestinal tract bleeding.

Blue rubber bleb nevus syndrome is a rare condition characterized by the presence of multiple angiomatic lesions of the skin. These are associated with similar lesions in other organs, namely in the gastrointestinal tract, causing anemia through chronic bleeding. We describe the case of a 72-year-old woman with microcytic anemia. A barium study revealed irregular lacunae in the distal esophagus. A subsequent endoscopy showed blue nodular lesions similar to angiomas of the esophagus and stomach fundus. Endosonography confirmed its angiomatic nature. Exploration of other organs, using magnetic resonance and cranial computed tomography, did not reveal the presence of this type of lesion. In physical examination, two angiomatic lesions were observed on the face and lips, respectively. These were blue in color and compressible, leaving an empty wrinkled sac that rapidly refilled, typical of angiomas.

Total agenesis of the left pericardium.

This is the report of a 46-year-old patient with the preoperative diagnosis of an atrial septal defect (ASD) of the ostium secudum type. After sternectomy, partial agenesis of the left pericardium was diagnosed. It is our opinion that, if the radiographic picture is suggestive of this entity, a clinical search for cardiopulmonary anomalies should be performed, because the majority of these associated anomalies can and should be surgically corrected.

Surgical revascularization of posterior coronary arteries without cardiopulmonary bypass.

OBJECTIVE: To assess the results observed during the early postoperative period in patients who had the posterior coronary arteries revascularized without cardiopulmonary bypass (CPB), in regard to the following parameters: age, sex, bypass grafts types, morbidity and mortality. METHODS: From January 1995 to June 1998, 673 patients underwent myocardial revascularization (MR). Of this total, 607 (90.20%) MR procedures were performed without CPB. The posterior coronary arteries (PCA) were revascularized in 298 (44.27%) patients, 280 (93.95%) without CPB. The age of the patients ranged from 37 to 88 years (mean, 61 years). The male gender predominated, with 198 men (70.7%). The revascularization of the posterior coronary arteries had the following distribution: diagonalis artery (31 patients, 10%); marginal branches of the circumflex artery (243 patients, 78.7%); posterior ventricular artery (4 patients, 1.3%); and posterior descending artery (31 patients, 10%). RESULTS: Procedure-related complications without death occurred in 7 cases, giving a morbidity of 2.5%. There were 11 deaths in the early postoperative period (mortality of 3.9%). CONCLUSION: Similarly to the anterior coronary arteries, the posterior coronary arteries may benefit from myocardial revascularization without CPB.

Maturation and aging-related differences in responsiveness of rat aorta and carotid arteries to alpha1-adrenoceptor stimulation.

Functional correlates of alpha1-adrenoceptors were studied in thoracic aorta and carotid arteries from Wistar rats, at maturation (3- and 8-week-old) and aging (17- and 29-week-old) phases, using phenylephrine (PHE) and KCl. PHE and KCl effects on rat aorta did not differ with age. A reduction in maximal contractions to PHE or KCl occurred in carotid arteries during maturation. Concentration-inhibition curves to the alkylating agent chloroethylclonidine or WB4101 suggested at all ages studied a predominance of alpha1B-adrenoceptors in aorta. However, alpha1A-adrenoceptors may account for some activity in aortas of 29-week-old rats. In carotid arteries alpha1D-adrenoceptors account for functional correlates at all ages studied. The results indicate that maturation or aging affects vascular responsiveness or predominant receptor subtype differently in aorta and carotid arteries with intact endothelium.

Mesenteric arteriovenous fistula causing portal hypertension and bleeding duodenal varices.

We report a case of portal hypertension associated with a non-traumatic arteriovenous fistula, presenting with bleeding duodenal varices. The patient was admitted for melaena. Emergency endoscopy showed oesophageal varices with no signs of recent bleeding and with no blood in the upper gastrointestinal tract. Arteriography of the coeliac axis and superior mesenteric artery failed to detect any bleeding source. Endoscopy was repeated because of persistent bleeding and revealed active bleeding from varices in the distal duodenum. The patient underwent surgery and a large paraduodenal varicose vein associated with an arteriovenous fistula was found. Resection of the paramural varix and surgical occlusion of the arteriovenous fistula were effective in the control of bleeding. Liver biopsy revealed mild portal fibrosis without cirrhosis. Three years after surgery the patient still has oesophageal varices but has not had recurrent bleeding. There was regression of intraduodenal varices.

Recurrence of a renal myogenic tumor presented as a duodenal ulcerated lesion.

BACKGROUND/AIM: The authors report on an extremely rare case of a recurrent myogenic tumor of renal origin presented exclusively with gastrointestinal signs and symptoms resulting from duodenal invasion. PATIENTS AND MATERIALS: A 49-year-old woman was admitted for epigastric pain and recent history of melenae. She had been submitted to right nefrectomy due to a smooth muscle tumor five years ago. RESULTS: Pathology described it as a bizarre leiomyoma. Diagnostic procedures showed lobulated and ulcerated lesions in the duodenum, a nodule within the anterior abdominal wall, a large neoplasm fulfilling the right renal loca and invading the duodenum, and another nodule at the left kidney. Histological features of all tumors were similar to those seen in the primary renal tumor. The abdominal wall nodule was the only resectable lesion. Although biopsies taken initially from the duodenal lesions failed to reveal smooth muscle tissue, they were repeated one year later and disclosed duodenal invasion from a leiomyosarcoma. CONCLUSION: This extremely rare case illustrates the striking disagreement between pathological diagnosis and clinical course of smooth muscle tumors that sometimes occur.

Endoscopic ultrasonography in the treatment of oesophageal varices by endoscopic sclerotherapy and band ligation: do we need it?

OBJECTIVE: To assess the role of endoscopic ultrasonography (EUS) in monitoring the treatment of oesophageal varices by endoscopic sclerotherapy and band ligation. METHODS: We studied 35 patients with portal hypertension undergoing elective treatment for oesophageal varices by injection sclerotherapy with absolute ethanol (group 1, n = 19) or by endoscopic variceal ligation (EVL; group 2, n = 16). All patients were examined by EUS before treatment to assess the status of their oesophago-gastric varices and the presence of collateral and perforating veins. Evaluation with EUS was repeated to confirm variceal eradication whenever endoscopy suggested successful obliteration, or to determine the reason for failure when treatment did not appear to be successful. Depending on the endosonographic findings, treatment was continued until EUS showed complete variceal eradication. RESULTS: After treatment, EUS showed insufficient variceal thrombosis in six (17%) patients who appeared to have variceal eradication at endoscopy. EUS was also superior to endoscopy for diagnosing gastric varices and showed patent vessels in 26 (74%) out of 35 patients. Gastric varices observed on EUS were detected at endoscopy in only 60% of cases. Endoscopic sclerotherapy and EVL had induced characteristic changes on EUS evaluation, and oesophageal fibrosis was observed more frequently in endoscopic sclerotherapy than in EVL-treated patients. CONCLUSION: EUS provides valuable information on the status of oesophago-gastric varices and can be used to assess the efficiency of endoscopic sclerotherapy and EVL.

[Secondary syphilis of gastric location]. / Sífilis secund ária de localização gástrica.

We present a case of syphilitic gastropathy manifested by an ulcero-infiltrative lesion in the gastric antrum in a 25 year old man. We obtained a clinical endoscopic cure with specific anti-luetic therapy. The morphologic characteristics, which are usual in this type of disease, are revised and the diagnostic criterion discussed.