Search

P-glycoprotein (P-gp), the product of ABCB1 gene, is thought to play a role in the biliary excretion of a variety of drugs, but specific studies in dogs have not been performed. Because a number of endogenous (ABCB1 polymorphisms) and exogenous (pharmacological P-gp inhibition) factors can interfere with normal P-gp function, a better understanding of P-gp's role in biliary drug excretion is crucial in preventing adverse drug reactions and drug-drug interactions in dogs. The objectives of this study were to compare biliary excretion of technetium-99m-sestamibi ((99m)Tc-MIBI), a radio-labelled P-gp substrate, in wild-type dogs (ABCB1 wild/wild), and dogs with intrinsic and extrinsic deficiencies in P-gp function. Dogs with intrinsic P-gp deficiency included ABCB1 mut/mut dogs, and dogs with presumed intermediate P-gp phenotype (ABCB1 mut/wild). Dogs with extrinsic P-gp deficiency were considered to be ABCB1 wild/wild dogs treated with the P-gp inhibitor ketoconazole (5 mg/kg PO q12h x 9 doses). Results from this study indicate that ABCB1 mut/mut dogs have significantly decreased biliary excretion of (99m)Tc-MIBI compared with ABCB1 wild/wild dogs. Treatment with ketoconazole significantly decreased biliary excretion of (99m)Tc-MIBI in ABCB1 wild/wild dogs. P-gp appears to play an important role in the biliary excretion of (99m)Tc-MIBI in dogs. It is likely that concurrent administration of a P-gp inhibitor such as ketoconazole will decrease P-gp-mediated biliary excretion of other substrate drugs as well.

Gaucher's disease (GD) is caused by a β-glucocerebrosidase deficiency, leading to the accumulation of glucocerebroside in the reticuloendothelial system. The prevalence of GD in Tabuleiro do Norte (TN) (1:4000) is the highest in Brazil. The purpose of this study was to present evidence of consanguinity and founder effect for the G377S mutation (c.1246GA) among GD patients in TN based on enzyme, molecular and genealogical studies. Between March 2009 and December 2010, 131 subjects at risk for GD (GC in dried blood ≤2.19 nmol/h/ml) and 5 confirmed GD patients from the same community were submitted for molecular analysis to characterize the genetic profile of the population. Based on the enzymatic and molecular analysis, the subjects were classified into three categories: affected (n = 5), carrier (n = 20) and non-carrier (n = 111). All carriers were (G377S/wt). Affected subjects were homozygous (G377S/G377S). The identification of a single mutation in carriers and homozygotes from different generations, the history of the community and the genealogy study suggest that the high prevalence of GD in this population may be due to a combination of consanguinity and founder effect for the G377S mutation.

Hepatocellular carcinoma is one of the most common malignancies worldwide. Liver transplantation has emerged as a good option for early-stage hepatocellular carcinoma yielding survival rates as good as for recipients without this type of tumor.To assess the outcome of cirrhotic patients with hepatocellular carcinoma undergoing liver transplantation at the Liver Transplantation Service of the "Hospital de Clinicas", Federal University of Paraná, Curitiba, PR, Brazil.Retrospective study of cirrhotic patients with hepatocellular carcinoma undergoing orthotopic liver transplantation at the mentioned Institution between September 1991 and September 2000. The diagnosis of hepatocellular carcinoma was established during the pretransplant workup in five patients and the tumor was an incidental finding in the native liver in three. The indication for liver transplantation was restricted to solitary tumor equal to or less than 5 cm or up to 3 nodules, with each nodule measuring less than 3 cm, and no evidence of vascular invasion or extrahepatic spread. Patient survival and evidence of tumoral recurrence posttransplant were evaluated.The most common cause for pretransplantation liver disease was hepatitis C virus (50%). On examination of the explanted liver, the majority of patients (6/8, 75%) had a single lesion; one patient had two nodules and one had a multifocal hepatocellular carcinoma found incidentally in the native liver. Tumor size ranged from 0.2 to 5.0 cm. All cases had neither vascular invasion nor linfonodal envolvement. All patients remained alive and free of tumor recurrence at the time of the study with a mean follow-up of 18.5 months (range, 5-29 months).Liver transplantation is a good therapeutic option for early stage hepatocellular carcinoma arising in cirrhotic patients. With proper selection, liver transplantation can offer excellent survival rates free of tumor recurrence.

Orthotopic liver transplantation is an established therapy for patients with end-stage liver disease. In the last years more attention has been given for the improvement of the quality of life after liver transplantation, and the return to important life pursuits, such as employment, are important goals of this type of therapy.To assess the work's return rate in liver transplant recipients and the reasons for inability after liver transplant.Forty-one adults (ageor = 18 years) who underwent liver transplantation at our institution, between September 1991 and June 1999, with a post-transplant survivalor = 9 months, good graft function and a regular clinical follow-up were enrolled for the study. A questionnaire that measured aspects of inactivity before and after liver transplantation had been applied.Thirty-one of 41 patients were unable to work due end-stage liver disease before liver transplantation. Return to work was observed in 28 of 41 patients (68%) in a mean time of 5.9 months after the surgical procedure. Eleven of 28 active patients after liver transplant (39%) contribute significantly to family income. The reasons for inactivity after liver transplantation were: early retirement (n = 5), unemployment (n = 4), and physical disability (n = 4).Successful liver transplantation not only improves the survival rate but allows patients to return to social function and workforce.

Free radicals superoxide (O(2)(-)) and nitric oxide (*NO) are generated by blood vessels and can rapidly react to produce a peroxynitrite anion (ONOO(-)), a powerful oxidant that modifies lipoproteins making them more atherogenic. The aim of this study was to investigate the effect of peroxynitrite-induced modifications on beta-very-low-density lipoprotein (beta-VLDL) as to its biodistribution and plasma clearance rate, as well as the uptake of these particles by THP-1 cells. After being injected into New Zealand White rabbits, the peroxynitrite-modified beta-VLDL (99mTc-per-beta-VLDL) was cleared from circulation faster than the native beta-VLDL (99mTc-nat-beta-VLDL) in both normocholesterolemic rabbits (NC) and in hypercholesterolemic rabbits (HC). In HC rabbits, the fractional clearance of 99mTc-labeled beta-VLDL was significantly lower than in NC rabbits. The in vivo studies showed that accumulation of 99mTc-labeled beta-VLDL, expressed per gram of tissue, followed the decreasing order: kidneyliverspleenadrenal glandor= lungaortic archheartor= abdominal aortathoracic aortapsoas muscle. The high accumulation in the kidneys suggests the processing of 99mTc-labeled apolipoproteins by receptors present in kidney cells. The accumulation of 99mTc-nat-beta-VLDL in the whole organ was the following: liverkidneyheartspleenadrenal glandaorta in HC and NC rabbits. The uptake of 99mTc-per-beta-VLDL by the spleen was greater than the uptake by the heart in both groups. The in vitro studies showed that the uptake of 99mTc-per-beta-VLDL by THP-1 cells was higher than that of 99mTc-nat-beta-VLDL. These results show that peroxynitrite-modified beta-VLDL is rapidly removed from plasma and accumulates in several tissues, mainly in the liver and kidney. This may be particularly important in hypercholesterolemic situations that could favor the accumulation of native and peroxynitrite-modified beta-VLDL in several tissues.

Benign recurrent intrahepatic cholestasis is a rare autosomal recessive disorder characterized by repeated episodes of intense pruritus and jaundice. Patients are completely asymptomatic for months to years between symptomatic periods. We report a case of a patient with a 7-year history of benign recurrent intrahepatic cholestasis. During the follow-up period the patient has suffered three attacks of cholestasis, confirmed by biochemical tests and histological exam. Liver enzymes were normal between the cholestasis episodes. Despite multiple attacks of cholestasis, no permanent liver damage has occurred. Although the diagnosis of benign recurrent intrahepatic cholestasis is rare, it should be included in the evaluation of a patient with cholestasis. The patients should be reassured of the benign course of this disorder.

Neutrophil accumulation in the first hour of myocardial reperfusion was assessed in dog hearts submitted to ischemia with and without necrosis. In anesthetized dogs, the left anterior descending coronary artery was occluded for 20 min (group IS-20 n = 7) and for 90 min (group IS-90 n = 6). Immediately after reperfusion, 99m Tc-Ceretec (Exametazime-Amersham) labeled neutrophils were injected into a central vein and 60 min later the dogs were killed. The left ventricle was isolated, weighed, and sliced. Six sections, 3 from normal and 3 from reperfused regions, were divided into endocardial and epicardial layers. Myocardial and blood radiometry were used to evaluate the neutrophil accumulation during reperfusion. The differences between leukocyte accumulation in both groups were assessed comparing the ischemic/ normal relations in the endocardial and epicardial layers. A second comparison considered myocardium/ blood relations to allow the evaluation of differences between remote normal myocardial areas of the two experimental groups. In dogs submitted to 20 min of ischemia, leukocytes accumulated significantly more (P < 0.01) in the reperfused myocardium as compared with the non-ischemic region. The increase occurred both in the endocardial (1.49 ± 0.20) and epicardial (1.48 ± 0.29) regions. After 90 min ischemia, leukocyte accumulation was more intense and predominant in endocardium where there was a 4-fold (3.97 ± 1.28) increase over the non-ischemic region, while in the epicardium this relation was only 2.5-fold (2.56 ± 0.98). In the remote non-ischemic myocardium, leukocyte accumulation was greater in dogs submitted to 90 min of ischemia compared to the 20 min group (P < 0.01), without distinction between endocardial and epicardial layers. This accumulation in territories of non-culprit coronary arteries may be related to the blood flow abnormalities and matrix structure changes that occur in these regions during the development of an acute myocardial infarction and its natural repair.

The objective of the present study was to determine the prevalence of gallstones in the population of Curitiba, Brazil. A total of 1000 persons was randomly recruited among individuals who were visiting two shopping centers of the city in order to represent the Brazilian population in relation to age and sex. The selected people underwent ultrasonographic examination of the upper abdomen immediately after a medical interview. Of the 1000 persons evaluated, 93 (9.3%) had gallstones (64 persons) or had been subjected to cholecystectomy due to cholelithiasis. The gallstone prevalence increased from 2.4% in persons of 20-29 years of age to 27.5% in persons of more than 70 years (chi2 = 37.29; P0.001). The prevalence was 2.4 greater in females (12.9%) than in males (5.4%) (chi2 = 16.34; P0.001). The prevalence increased with the number of pregnancies from 4% in nulliparous women, to 34.6% in persons with a history of six or more pregnancies (chi2 = 200.1; P0,001). The prevalence also increased according to the body weight (chi2 = 30.08; P0.001). There was no difference in the prevalence between individuals with diabetes mellitus and controls. It is concluded from this study that the prevalence of gallstones in the city of Curitiba is elevated.

A patient with a history of intermittent and intense pain in the upper abdomen secondary to an ulcer of a duodenal diverticulum underwent laparoscopic treatment. The diverticulum measured 2.5 cm in diameter and it was located on the lateral wall of the second portion of the duodenum. The diverticulum was inverted and the duodenal muscular defect was closed with interrupted sutures. Ambulation and a clear liquid diet was started on the same day as the operation, and the patient was discharged on the first postoperative day.

To determine the cost of liver transplantation at the Clinical Hospital of the Federal University of Parana.The data of 24 patients subjected to 25 liver transplantations were evaluated from the day of hospital admission until the day of discharge to determine the length of hospitalization, quantity of material and medications used, and exams and procedures performed. Professional fees were not included in the study.The age of the patients varied from 6 to 56 years. Six patients were younger than 14 years of age. Five patients died during hospitalization. Retransplantation was performed in only one patient. The average cost for liver procurement was US$ 2,783.19. The total cost of the liver transplantation varied, depending on the occurrence of complications, length of hospitalization and the amount of blood products transfused. The total cost varied from US$ 6,359.84 to US$ 75,434.18, with an average of US$ 21,505.53. The most expensive item of the liver transplantation was blood products transfused, followed by medications, and intensive care and room charges.The cost of liver transplantation varies among the patients and may be performed in Brazil at a cost less than that reported in the United States and Europe.

In pressure-driven hemorrhage (PDH), where the rate of bleeding is a function of prevailing arterial pressure, survival time, arterial pressure, cardiac output, oxygen consumption, and base excess are functions of initial bleeding rate. The quantitative rate of transcapillary refill (TR) throughout PDH leading to death was determined in splenectomized dogs, through serial analysis of Cr51-tagged red cell dilution. Mild, moderate, and severe levels of PDH were produced by varying initial bleeding rate (10, 25, and 50 ml/min, respectively). The rate of TR is a function of the severity of PDH, but does not correlate with arterial pressure, cardiac output, or systemic resistance. The volume of transferred fluid represents an ever increasing fraction of total plasma volume, and accounts for more than 75% of plasma volume in preterminal stages of shock. TR sustains a relatively fixed level of plasma volume, equivalent to two-third of the initial plasma volume, irrespective of the rate of bleeding. Hypertonic NaCl (7.5%) enhances TR, while isotonic NaCl reverses it.

To present our experience of progressive preoperative pneumoperitoneum in the preparation of patients for repair of large hernias of the abdominal wall.Prospective selected series.A university hospital and a district hospital.36 Patients of the 252 who presented for abdominal hernia repair between January 1977 and April 1992.Air was insufflated into the peritoneal cavity through a 19 gauge spinal needle, and between 500 and 2000 ml was usually injected at the first session. Amounts were gradually increased daily or every other day for a period of 6-15 days; the total amount insufflated ranged from 4500-18,500 (mean 7700) ml.Whether the hernia could be repaired directly without recourse to polypropylene mesh, complications of pneumoperitoneum, and recurrence rate.In one patient air was insufflated into the colon, one developed temporary but severe respiratory distress, and 4 developed moderate subcutaneous emphysema. 30 hernias were repaired directly, and 6 required polypropylene mesh. There were three wound infections (two after direct repair), and two recurrences (both after direct repair). Mean length of follow up was 10 months (range 1-48).Progressive preoperative pneumoperitoneum allows direct repair of some large abdominal hernias with a low recurrence rate, and few complications.

The prevalence of gallstones was determined in Curitiba. A total of 384 patients older than 20 years of age was randomly selected from four general hospitals and subjected to ultrasonographic examination of the gallbladder. Of the 384 patients, 327 had normal gallbladder (85.2%) and 57 (14.8%) had gallstones (48 patients) or had been previously subjected to cholecystectomy due to gallstones (9 patients). Six out of the 48 patients with gallstones referred biliary colic (12.5%). Gallstone prevalence increased with age and number of pregnancies.

Thirty-two patients with acute acalculous cholecystitis are presented. The age of the patients ranged from 1 to 80 years, with an average of 46.3 years. Acute acalculous cholecystitis occurred during the postoperative period in only four patients. Three patients were receiving total parenteral nutrition and 16 patients had one or more associated medical diseases. One patient had acute acalculous cholecystitis due to mechanical obstruction of the cystic duct caused by a diaphragmatic hernia. The most frequent signs and symptoms were right upper quadrant abdominal pain, nausea, vomiting, fever, abdominal mass, and jaundice. All patients were subjected to cholecystectomy. Nine (28.1%) gallbladder specimens had gangrene. Pericholecystic perforation was observed in four patients (12.5%) free perforation in one patient (3.1%), and empyema of the gallbladder in one patient (3.1%). Bacteria were cultured from 18 of 24 bile specimens. E. coli was the most common organism isolated. The overall postoperative mortality and complication rates were 15.6% and 40.6% respectively. The average hospital stay was 16.4 days.

The skin microbial flora of 18 patients was evaluated during prolonged preoperative hospital stay. Five cultures for bacteria and fungi were obtained on different days: on admission one, three and seven days after admission and after skin disinfection with povidone-iodine solution. There was no change in the mean bacterial count from the admission day to seven days after admission. All but one culture obtained following skin disinfection were negative. Pathogenic bacteria were isolated in only one of each of the following culture day: admission, three and seven days after admission. All cultures were negative for yeasts. The findings suggest that the higher rate of wound sepsis observed in patients with long preoperative hospitalization may not be due to bacterial flora change.

In this study, a series of 705 patients with chronic cholecystitis and 203 with acute cholecystitis were surgically treated. The age distribution for the two groups was similar. Operative cholangiography was performed upon 661 patients (94.0 per cent) with chronic cholecystitis and upon 182 patients (90 per cent) with acute cholecystitis. The common bile duct was explored in 146 patients (20.7 per cent) with chronic cholecystitis and in 41 patients (20.1 per cent) with acute cholecystitis, and bile duct calculi were found in 106 patients (15 per cent) with chronic cholecystitis and in 29 patients (14.2 per cent) with acute inflammation of the gallbladder. The total number of postoperative complications and the operative mortality were similar for the two groups. It is concluded that the incidence of common bile duct stones in patients with acute cholecystitis is the same as for those with chronic cholecystitis.

Myoelectric activity of the sphincter of Oddi and duodenum was correlated with pancreatic and biliary duct pressures in eight opossums, in both the fasted and fed states. Four bipolar electrode pairs were implanted in the sphincter of Oddi and duodenum. A polyethylene T tube was placed in the pancreatic duct. The common duct was cannulated through a small bile duct. This method allowed pressure recording for several weeks and avoided interference with the flow of bile or pancreatic juice into the duodenum. The frequency of slow waves was the same in the sphincter of Oddi and duodenum (19 per minute). The variation in the frequency of spike potentials in the sphincter of Oddi correlated to that of the migrating myoelectric complex in the duodenum. The average frequency of slow waves that have superimposed spike potentials in the sphincter of Oddi and duodenum was 3.0 and 0 in phase 1, 4.7, and 6.2 in phase II, 6.1 and 15.1 in phase III, and 3.4 and 6.3 in phase IV, respectively. The average duration of a migrating myoelectric complex cycle was 92 minutes. After feeding, the interdigestive phases of the migrating myoelectric complex were abolished and substituted by a feeding activity pattern that was characterized by an average number of sphincter of Oddi and duodenum spikes of 6.6 and 10.7, respectively. The mean fasting pressure in the pancreatic and biliary duct was 15 and 13 mmHg, respectively. Pressure changes were of two types--synchronous with respiratory movements and with each sphincter of Oddi spike potential. There was no variation in the baseline pressure during the migrating myoelectric complex phases and the fed state. It is concluded that the sphincter of Oddi of the fasting opossum exhibits cyclic changes in the number of spike potentials that correlate with the migrating myoelectric complex in the duodenum. However, the number and amplitude of spike potentials are different in the sphincter of Oddi and duodenum. There is no change in the baseline pressure during fasting and feeding states, and a temporary pressure elevation synchronic with each sphincter of Oddi spike potential was observed.

The accuracy of arteriography in detecting vascular defects similar to those encountered during vascular surgery was evaluated experimentally. Intimal flaps, thrombi, and strictures were created in dog aortas and studied under circumstances resembling operating room conditions by single-view portable and serial biplanar contrast arteriography. The specificity of both types of arteriography was comparable and high for detecting vascular defects. The sensitivity for diagnosing strictures was also comparable and high. However, both radiographic techniques were relatively insensitive in the detection of small intimal flaps and thrombi. In the detection of these two types of defects, serial biplanar arteriography was significantly more sensitive than portable arteriography. The degree of the superiority of serial bi-plane and the possible clinical insignificance of small defects indicates that portable arteriography in the operating room may still be an adequate methodology.

We have evaluated the effect of various autonomic drugs on the electromyographic activity of the sphincter of Oddi and the small intestine of seven opossums. Hexamethonium bromide and atropine sulfate abolished and bethanechol increased the frequency of spike bursts in the sphincter of Oddi and duodenum. Phenylephrine and epinephrine increased the number of spike bursts in the sphincter of Oddi after a short period of stimulation. No spike potentials were seen in the duodenum after infusion of norepinephrine. Clonidine and dobutamine decreased spike burst activity in the sphincter of Oddi and duodenum. Terbutaline also decreased the frequency of spike bursts in the sphincter of Oddi but did not change the number in the duodenum. Prior infusion of antagonists blocked partially or totally the effect of all respective agonists except for yohimbine, which did not inhibit the effect of clonidine. These findings suggest that the sphincter of Oddi may have cholinergic, alpha 1, alpha 1, beta 1 and beta 2-adrenergic receptors. Cholinergic agonists stimulate and alpha 2, beta 1 and beta 2-adrenergic agonists inhibit the motility of the sphincter of Oddi and the small intestine. Alpha-adrenergic agonists stimulate the motility of the sphincter of Oddi and inhibit the motility of the small intestine.

Four cases of rhynoentomophthoramycosis are reported from urban areas of the states of Bahia and Maranhão, Brazil. The lesions presented with infiltration, redness and heat of the skin of the nose and infraorbital areas and accompanying nasal stuffiness. In on case the infiltration also involved the lips and mandibular area causing severe facial deformity. Microscopically, granulomatous reactions with small abcesses, fibrosis and a dense infiltration of eosinophils were found. Hyphae were seen frequently, always associated with the Splendore phenomenon. Three cases were treated completely with iodine. The one case resistant to iodine was cured with prolonged administration of sulphona. In two cases, plastic surgery was performed for facial reconstruction and nasal-unblocking respectively. Including the cases presented here, only 8 cases of rhynoentomophthoramycosis have been reported in Brazil, but the authors believe that this pathology muta occur more frequently. The lack of knowledge of its clinico-pathological aspects may be responsible for the delay or lack of diagnosis of this entity which occurred in two of the cases reported here.

A case of gastroatrial fistula following resection of a carcinoma of the mid-esophagus and re-establishment of the alimentary tract with a cervical esophagogastrostomy is presented. Three episodes of moderate upper gastrointestinal hemorrhage secondary to chronic peptic ulcer of the stomach placed in the thorax occurred three years after the operation. At this time, the patient was also admitted to the hospital with diagnosis of pericarditis of unknown etiology. Three years later the patient had a massive and fatal episode of upper gastrointestinal bleeding.

Pancreatitis was induced in the opossum by occluding the common bile duct above or below the entrance of the pancreatic duct. The common channel theory was tested by evaluating the effect of preligation of the pancreatic duct to prevent the reflux of bile after ligation of the distal common duct. The severity of the disease was determined by histologic grading of the degree of pancreatic tissue necrosis. Serum amylase, lipase, and calcium were determined. Concomitant obstruction of the biliary and pancreatic ducts produced severe necrotizing pancreatitis whether or not bile reflux was present. Pancreatic ductal obstruction alone was associated with acinar atrophy and mild interstitial pancreatitis. Biliary obstruction alone above the entrance of the pancreatic duct resulted in marked hyperemia of the gland but without histologic evidence of pancreatic inflammation. A positive bacterial culture of the pancreas was obtained in only four of 36 opossums in a distribution to suggest random contamination. There was an inverse correlation between calcium levels and the degree of tissue necrosis. This study demonstrates that biliary obstruction rather than bile reflux into the pancreas is a requisite for the pathogenesis of severe biliary pancreatitis in this model.