Bile duct stones, strictures and iatrogenic lesions: studies on early diagnosis and treatment.

Aims: This study was carried out to investigate the role of common liver function tests, and the degree of common bile duct dilatation in the differential diagnosis of extrahepatic cholestasis, as well as the occurrence, diagnosis and treatment of iatrogenic bile duct injuries. In bile duct injuries, special attention was paid to gender and severity distribution and long-term results. Patients and methods: All consecutive patients with diagnosed common bile duct stones or malignant strictures in ERCP between August 2000 and November 2003. Common liver function tests were measured in the morning before ERCP on all of these 212 patients, and their common bile duct diameter was measured from ERCP films. Between January 1995 and April 2002, 3736 laparoscopic cholecystectomies were performed and a total of 32 bile duct injuries were diagnosed. All pre-, per-, and postoperative data were collected retrospectively; and the patients were also interviewed by phone. Results: Plasma bilirubin proved to be the best discriminator between CBD stones and malignant strictures (p≤0.001 compared to other liver function tests and degree of common bile duct dilatation). The same effect was seen in Receiver Operating Characteristics curves (AUC 0.867). With a plasma bilirubin cut-off value of 145 μmol/l, four out of five patients could be classified correctly. The degree of common bile duct dilatation proved to be worthless in differential diagnostics. After laparoscopic cholecystectomy the total risk for bile duct injury was 0.86%, including cystic duct leaks. 86% of severe injuries and 88% of injuries requiring operative treatment were diagnosed in females. All the cystic duct leakages and 87% of the strictures were treated endoscopically. Good long-term results were seen in 84% of the whole study population. Conclusions: Plasma bilirubin is the most effective liver function test in differential diagnosis between CBD stones and malignant strictures. The only value of common bile duct dilatation is its ability to verify the presence of extrahepatic cholestasis. Female gender was associated with higher number of iatrogenic bile duct injuries, and in particular, most of the major complications occur in females. Most of the cystic duct leaks and common bile duct strictures can be treated endoscopically. The long-term results in our institution are at an internationally acceptable level.

The role of executive functions in the control of aggressive behavior

An extensive literature suggests a link between executive functions and aggressive behavior in humans, pointing mostly to an inverse relationship, i.e., increased tendencies toward aggression in individuals scoring low on executive function tests. This literature is limited, though, in terms of the groups studied and the measures of executive functions. In this paper, we present data from two studies addressing these issues. In a first behavioral study, we asked whether high trait aggressiveness is related to reduced executive functions. A sample of over 600 students performed in an extensive behavioral test battery including paradigms addressing executive functions such as the Eriksen Flanker task, Stroop task, n-back task, and Tower of London (TOL). High trait aggressive participants were found to have a significantly reduced latency score in the TOL, indicating more impulsive behavior compared to low trait aggressive participants. No other differences were detected. In an EEG-study, we assessed neural and behavioral correlates of error monitoring and response inhibition in participants who were characterized based on their laboratory-induced aggressive behavior in a competitive reaction time task. Participants who retaliated more in the aggression paradigm and had reduced frontal activity when being provoked did not, however, show any reduction in behavioral or neural correlates of executive control compared to the less aggressive participants. Our results question a strong relationship between aggression and executive functions at least for healthy, high-functioning people.

Gravidez após transplante hepático

The objective of the present study is to report a sucessful pregnancy in a 28 year-old female who underwent an orthotopic liver transplantation two years ago due to type I auto immune he patitis. Patient was taking cyclosporin, prednisone and azathioprine for maintenance immunossupression and had good graft function during all the pregnancy. The liver function tests were normal during the pregnancy. Fetal growth was monitored by ultrasonographic examination and showed normal development. At the end of the third trimester, she was subjected to a cesarean bearing a healthy girl weighting 2,320 kg. She was discharged with normal liver functions tests and no complications.

Tuberculose hepática pseudotumoral

Tuberculous involvement of the liver is usually a diffuse process, associated with miliary tuberculosis. However localized tuberculosis of the liver producing a macronodular tuberculoma or an abscess is rare. The authors present a case of pseudotumoral hepatic tuberculosis in a 34-year old woman. This patient presented a 2 month history of fever weight loss of 4Kg and right upper quadrant abdominal pain. She denied jaundice, choluria, or acholia. Laboratory investigation, including renal and liver function tests. revealed normal levels. Chest X-ray was normal. Abdominal ultrasonography demonstrated a hypoechoic nodule in the right hepatic lobe. CT scan showed hypodense areas in the same place and no retroperitoneal lymphadenopathy. Due to the inespecificity of the signs, symptoms and image findings, a diagnostic laparoscopy was performed, it was however inconclusive. Then, the patient was submitted to a laparotomy with ressection of the lesion. Histological examination revealed a tuberculoid granulomatous lesion with caseous necrosis. Postoperatively, the patient was placed on antituberculous chemotherapy with rifampin, isoniazid and pyrazinamide. Eight months later the patient is asymptomatic.

Pseudotumor inflamatório do fígado: diagnóstico diferencial de carcinoma hepatocelular

The authors present a rare case of inflammatory pseudotumor of the liver whose differential diagnosis with hepatocellular carcinoma - in some cases - is only possible with the histological examination. In this case, a female patient, 38 years-old was suffering from abdominal pain, enlarged liver, thinning, tiredness and fever; alpha-fetoprotein, the liver function tests, amylase and lipase were normal. Abdominal ultrasound and computed tomography showed a node in the right liver lobe. The patient was submitted to a right hepatectomy for hepatocellular carcinoma. Histological examination showed an inflammatory pseudotumor of the liver. The patient was discharged from the hospital on the seventh postoperative day; she is asymptomatic for three years.

The use of dietary supplements and medication among Finnish elite athletes

Background: Dietary supplements are widely used among elite athletes but the prevalence of dietary supplement use among Finnish elite athletes is largely not known. The use of asthma medication is common among athletes. In 2009, the World Anti-Doping Agency (WADA) and the International Olympic Committee (IOC) removed the need to document asthma by lung function tests before the use of inhaled β2-agonists. Data about medication use by Paralympic athletes (PA) is limited to a study conducted at the Athens Paralympics. Aims: To investigate the prevalence of the use of self-reported dietary supplements, the use of physician-prescribed medication and the prevalence of physician-diagnosed asthma and allergies among Finnish Olympic athletes (OA). In addition, the differences in the selfreported physician-prescribed medication use were compared between the Finnish Olympic and the Paralympic athletes. Subjects and methods: Two cross-sectional studies were conducted in Finnish Olympic athletes receiving financial support from the Finnish Olympic Committee in 2002 (n=446) and in 2009 (n=372) and in Finnish top-level Paralympic athletes (n= 92) receiving financial support from Finnish Paralympic committee in 2006. The results of the Paralympic study were compared with the results of the Olympic study conducted in 2009. Both Olympic and Paralympic athletes filled in a similar semi-structured questionnaires. Results: Dietary supplements were used by 81% of the athletes in 2002 and by 73% of the athletes in 2009. After adjusting for age-, sex- and type of sport, the odds ratio OR (95% confidence interval, CI) for use of any dietary supplement was significantly less in 2009 as compared with the 2002 situation (OR 0.62; 95% CI 0.43-0.90). Vitamin D was used by 0.7% of the athletes in year 2002 but by 2% in 2009 (ns, p = 0.07). The use of asthma medication increased from 10.4 % in 2002 to 13.7% in 2009 (adjusted OR 1.71; 95% CI 1.08-2.69). For example, fixed combinations of inhaled long-acting β2-agonists (LABA) and inhaled corticosteroids (ICS) were used three times more commonly in 2009 than in 2002 (OR 3.38; 95% CI 1.26-9.12). The use of any physician-prescribed medicines (48.9% vs. 33.3%, adjusted OR 1.99; 95% CI 1.13-3.51), painkilling medicines (adjusted OR 2.61; 95% CI 1.18-5.78), oral antibiotics (adjusted OR 4.10; 95% CI 1.30-12.87) and anti-epileptic medicines (adjusted OR 37.09; 95% CI 5.92-232.31) was more common among the PA than in the OA during the previous seven days. Conclusions: The use of dietary supplements is on the decline among Finnish Olympic athletes. The intake of some essential micronutrients, such as vitamin D, is suprisingly low and this may even cause harm in those well-trained athletes. The use of asthma medication, especially fixed combinations of LABAs and ICS, is clearly increasing among Finnish Olympic athletes. The use of any physician-prescribed medicine, especially those to treat chronic diseases, seems to be more common among the Paralympians than in the Olympic athletes.

Motoneuronitautiin liittyvä hengitysvajaus: hengitystoiminnan ja energia-aineenvaihdunnan mittaaminen

Tavoitteet: Tämän tutkimussarjan tavoitteena oli tutkia hengitystoiminnan sekä energia-aineen¬vaihdunnan muutoksia motoneuronitautia (amyotrofinen lateraaliskleroosi, ALS) sairastavilla potilailla. Erityisenä mielenkiinnon kohteena olivat kotihoitoon soveltuvan hengityslaitteen vai¬kutus elinajan ennusteeseen sekä hengitysvajauksen etenemistä kuvaavien keuhkotoimintakokei¬den arviointi ALS-potilailla, epäsuoran kalorimetrian mittaustarkkuus ja perusaineenvaihdunnan (PAV) suuruus kajoavaa hengityslaitetta käyttävillä ALS-potilailla. Aineisto ja menetelmät: Kajoamattoman hengityslaitteen käytön ja iän vaikutusta elinajan en¬nusteeseen arvioitiin 84:llä ja hengitystoiminnan muutoksia 42 ALS-potilaalla. Epäsuoran kalo¬rimetrian mittaustarkkuutta kajoamatonta hengityslaitetta käytettäessä arvioitiin hereillä olevilla 12 vapaaehtoisella mieshenkilöllä. PAV:n suuruutta arvioitiin viidellä kajoavaa hengityslaitetta käyttävällä ALS-potilaalla. Osatöistä kaksi ensimmäistä olivat luonteeltaan havainnoivia (retros¬pektiivisiä) ja kaksi viimeistä seurantatutkimuksia (prospektiivisia). Tulokset: Alle 65-vuotiailla ALS-potilailla ei havaittu eroa elinajan ennusteessa kajoamaton¬ta hengityslaitetta käyttävien ja käyttämättömien potilaiden välillä. Sen sijaan yli 65-vuotiail¬la ALS-potilailla elinajan ennuste piteni merkittävästi kajoamatonta hengityslaitetta käyttävillä potilailla (elinaika diagnoosin jälkeen 22 vs. 8 kk, Hazard Ratio = 0.25, 95 % luottamusväli 0.11 – 0.55, p <0.001). ALS-potilailla, joilla kajoamaton hengityslaite katsottiin tarpeelliseksi kuuden kuukauden kuluessa diagnoosihetkestä, hengitystiheys osoittautui diagnoosihetkellä mer-kittävästi kiihtyneeksi (21/min) ja rintakehän liike merkittävästi alentuneeksi (2.9 cm) verrattuna ALS-potilaisiin, joille kajoamaton hengityslaite katsottiin tarpeelliseksi myöhemmin (16/min ja 4.0 cm). Kajoamattoman hengityslaitehoidon aikana keskimääräinen mitattu PAV vapaaehtoisilla miehillä oli 1858 kcal/vrk kun PAV ilman hengityslaitetta oli 1852 kcal/vrk, p = 0.8. Kajoavaa hengityslaitehoitoa käyttävien viiden ALS-potilaan keskimääräinen PAV vastaavalla mittausase¬telmalla mitattaessa oli 1130 kcal/vrk, kun vastaava PAV laskettuna viidellä eri laskentakaavalla oli 1700 kcal/vrk, p < 0.001. Johtopäätökset: Yli 65-vuotiailla ALS-potilailla, jotka eivät sopeutuneet kajoamattomaan hen¬gityslaitehoitoon, oli nelinkertainen riski menehtyä aiemmin kuin kajoamattomaan hengityslai¬tehoitoon sopeutuneilla ALS-potilailla. Hengitystiheys osoittautui merkittävästi kiihtyneeksi ja rintakehän liike alentuneeksi ALS-potilailla, joille kajoamaton hengityslaitehoito katsottiin ai¬heelliseksi kuuden kuukauden kuluessa diagnoosihetkestä. Kajoamattoman hengityslaitehoidon aikana mitattu PAV ei poikennut mitatusta PAV:sta itsenäisen hengityksen aikana. Näin ollen epäsuoraa kalorimetriamenetelmää voidaan käyttää luotettavasti PAV:n määrittämiseen käytet¬täessä samanaikaisesti kotihoitoon soveltuvaa hengityslaitehoitoa. Elämää ylläpitävää kajoavaa hengityslaitehoitoa käyttävien ALS-potilaiden PAV oli merkittävästi hidastunut laskennallisella menetelmällä arvioituun PAV verrattuna.

Effect of inhibition of nitric oxide synthase on blood pressure and renal sodium handling in renal denervated rats

The role of sympathetic nerve activity in the changes in arterial blood pressure and renal function caused by the chronic administration of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, was examined in sham and bilaterally renal denervated rats. Several studies have demonstrated that sympathetic nerve activity is elevated acutely after L-NAME administration. To evaluate the role of renal nerve activity in L-NAME-induced hypertension, we compared the blood pressure response in four groups (N = 10 each) of male Wistar-Hannover rats weighing 200 to 250 g: 1) sham-operated vehicle-treated, 2) sham-operated L-NAME-treated, 3) denervated vehicle-treated, and 4) denervated L-NAME-treated rats. After renal denervation or sham surgery, one control week was followed by three weeks of oral administration of L-NAME by gavage. Arterial pressure was measured weekly in conscious rats by a tail-cuff method and renal function tests were performed in individual metabolic cages 0, 7, 14 and 21 days after the beginning of L-NAME administration. L-NAME (60 mg kg-1 day-1) progressively increased arterial pressure from 108 ± 6.0 to 149 ± 12 mmHg (P<0.05) in the sham-operated group by the third week of treatment which was accompanied by a fall in creatinine clearance from 336 ± 18 to 222 ± 59 µl min-1 100 g body weight-1 (P<0.05) and a rise in fractional urinary sodium excretion from 0.2 ± 0.04 to 1.62 ± 0.35% (P<0.05) and in sodium post-proximal fractional excretion from 0.54 ± 0.09 to 4.7 ± 0.86% (P<0.05). The development of hypertension was significantly delayed and attenuated in denervated L-NAME-treated rats. This was accompanied by a striking additional increase in fractional renal sodium and potassium excretion from 0.2 ± 0.04 to 4.5 ± 1.6% and from 0.1 ± 0.015 to 1.21 ± 0.37%, respectively, and an enhanced post-proximal sodium excretion compared to the sham-operated group. These differences occurred despite an unchanged creatinine clearance and Na+ filtered load. These results suggest that bilateral renal denervation delayed and attenuated the L-NAME-induced hypertension by promoting an additional decrease in tubule sodium reabsorption in the post-proximal segments of nephrons. Much of the hypertension caused by chronic NO synthesis inhibition is thus dependent on renal nerve activity.

Patient and physician evaluation of the severity of acute asthma exacerbations

We studied the ability of patients not experienced in the use of peak expiratory flow meters to assess the severity of their asthma exacerbations and compared it to the assessment of experienced clinicians. We also evaluated which data of physical examination and medical history are used by physicians to subjectively evaluate the severity of asthma attacks. Fifty-seven adult patients (15 men and 42 women, with a mean (± SD) age of 37.3 ± 14.5 years and 24.0 ± 17.9 years of asthma symptoms) with asthma exacerbations were evaluated in a University Hospital Emergency Department. Patients and physicians independently evaluated the severity of the asthma attack using a linear scale. Patient score, physician score and forced expiratory volume at the first second (FEV1) were correlated with history and physical examination variables, and were also considered as dependent variables in multiple linear regression models. FEV1 correlated significantly with the physician score (rho = 0.42, P = 0.001), but not with patient score (rho = 0.03; P = 0.77). Use of neck accessory muscles, expiratory time and wheezing intensity were the explanatory variables in the FEV1 regression model and were also present in the physician score model. We conclude that physicians evaluate asthma exacerbation severity better than patients and that physician's scoring of asthma severity correlated significantly with objective measures of airway obstruction (FEV1). Some variables (the use of neck accessory muscles, expiratory time and wheezing intensity) persisted as explanatory variables in physician score and FEV1 regression models, and should be emphasized in medical schools and emergency settings.

Efficacy of the FEV1/FEV6 ratio compared to the FEV1/FVC ratio for the diagnosis of airway obstruction in subjects aged 40 years or over

The present cross-sectional, population-based study was designed to evaluate the performance of the FEV1/FEV6 ratio for the detection of airway-obstructed subjects compared to the FEV1/FVC <0.70 fixed ratio test, as well as the lower limit of normality (LLN) for 1000 subjects ³40 years of age in the metropolitan area of São Paulo, SP, Brazil. After the exclusion of 37 (3.7%) spirometries, a total of 963 pre-bronchodilator (BD) and 918 post-BD curves were constructed. The majority of the post-BD curves (93.1%) were of very good quality and achieved grade A (762 curves) or B (93 curves). The FEV1/FEV6 and FEV1/FVC ratios were highly correlated (r² = 0.92, P < 0.000). Two receiver operator characteristic curves were constructed in order to express the imbalance between the sensitivity and specificity of the FEV1/FEV6 ratio compared to two FEV1/FVC cut-off points for airway obstruction: equal to 70 (area under the curve = 0.98, P < 0.0001) and the LLN (area under the curve = 0.97, P < 0.0001), in the post-BD curves. According to an FEV1/FVC <0.70, the cut-off point for the FEV1/FEV6 ratio with the highest sum for sensitivity and specificity was 0.75. The FEV1/FEV6 ratio can be considered to be a good alternative to the FEV1/FVC ratio for the diagnosis of airway obstruction, both using a fixed cut-off point or below the LLN as reference. The FEV1/FEV6 ratio has the additional advantage of being an easier maneuver for the subjects and for the lung function technicians, providing a higher reproducibility than traditional spirometry maneuvers.

Factors associated with uncontrolled asthma in Porto Alegre, Brazil

The prevalence of uncontrolled and controlled asthma, and the factors associated with uncontrolled asthma were investigated in a cross-sectional study. Patients aged 11 years with confirmed asthma diagnosis were recruited from the outpatient asthma clinic of Hospital de Clínicas de Porto Alegre, Brazil. Patients were excluded if they had other chronic pulmonary disease. They underwent an evaluation by a general questionnaire, an asthma control questionnaire (based on the 2006 Global Initiative for Asthma guidelines), assessment of inhaled device technique and pulmonary function tests. Asthma was controlled in 48 of 275 patients (17.5%), partly controlled in 74 (26.9%) and uncontrolled in 153 (55.6%). In the univariate analysis, asthma severity was associated with asthma control (P < 0.001). Availability of asthma medications was associated with asthma control (P = 0.01), so that most patients who could purchase medications had controlled asthma, while patients who depend on the public health system for access to medications had lower rates of controlled asthma. The use of inhaled corticosteroid was lower in the uncontrolled group (P < 0.001). Logistic regression analysis identified three factors associated with uncontrolled asthma: severity of asthma (OR = 5.33, P < 0.0001), access to medications (OR = 1.97, P = 0.025) and use of inhaled corticosteroids (OR = 0.17, P = 0.030). This study showed a high rate of uncontrolled asthma in patients who attended an outpatient asthma clinic. Severity of asthma, access to medications and adequate use of inhaled corticosteroids were associated with the degree of asthma control.

Outcomes and organ dysfunctions of critically ill patients with systemic lupus erythematosus and other systemic rheumatic diseases

Our objective was to compare the pattern of organ dysfunctions and outcomes of critically ill patients with systemic lupus erythematosus (SLE) with patients with other systemic rheumatic diseases (SRD). We studied 116 critically ill SRD patients, 59 SLE and 57 other-SRD patients. The SLE group was younger and included more women. Respiratory failure (61%) and shock (39%) were the most common causes of ICU admission for other-SRD and SLE groups, respectively. ICU length-of-stay was similar for the two groups. The 60-day survival adjusted for the groups’ baseline imbalances was not different (P = 0.792). Total SOFA scores were equal for the two groups at admission and during ICU stay, although respiratory function was worse in the other-SRD group at admission and renal and hematological functions were worse in the SLE group at admission. The incidence of severe respiratory dysfunction (respiratory SOFA >2) at admission was higher in the other-SRD group, whereas severe hematological dysfunction (hematological SOFA >2) during ICU stay was higher in the SLE group. SLE patients were younger and displayed a decreased incidence of respiratory failure compared to patients with other-SRDs. However, the incidences of renal and hematological failure and the presence of shock at admission were higher in the SLE group. The 60-day survival rates were similar.

Morphometric evaluation of nitric oxide synthase isoforms and their cytokine regulators predict pulmonary dysfunction and survival in systemic sclerosis

Because histopathological changes in the lungs of patients with systemic sclerosis (SSc) are consistent with alveolar and vessel cell damage, we presume that this interaction can be characterized by analyzing the expression of proteins regulating nitric oxide (NO) and plasminogen activator inhibitor-1 (PAI-1) synthesis. To validate the importance of alveolar-vascular interactions and to explore the quantitative relationship between these factors and other clinical data, we studied these markers in 23 cases of SSc nonspecific interstitial pneumonia (SSc-NSIP). We used immunohistochemistry and morphometry to evaluate the amount of cells in alveolar septa and vessels staining for NO synthase (NOS) and PAI-1, and the outcomes of our study were cellular and fibrotic NSIP, pulmonary function tests, and survival time until death. General linear model analysis demonstrated that staining for septal inducible NOS (iNOS) related significantly to staining of septal cells for interleukin (IL)-4 and to septal IL-13. In univariate analysis, higher levels of septal and vascular cells staining for iNOS were associated with a smaller percentage of septal and vascular cells expressing fibroblast growth factor and myofibroblast proliferation, respectively. Multivariate Cox model analysis demonstrated that, after controlling for SSc-NSIP histological patterns, just three variables were significantly associated with survival time: septal iNOS (P=0.04), septal IL-13 (P=0.03), and septal basic fibroblast growth factor (bFGF; P=0.02). Augmented NOS, IL-13, and bFGF in SSc-NSIP histological patterns suggest a possible functional role for iNOS in SSc. In addition, the extent of iNOS, PAI-1, and IL-4 staining in alveolar septa and vessels provides a possible independent diagnostic measure for the degree of pulmonary dysfunction and fibrosis with an impact on the survival of patients with SSc.

La transplantation d’hépatocytes chez le rat Long Evans Cinnamon, modèle animal de la maladie de Wilson

La maladie de Wilson est une maladie héréditaire due à un déficit du transporteur du cuivre, l’ATP7B. Cette maladie se présente sous forme d’insuffisance hépatique aiguë ou chronique, pour lesquels le traitement médical actuel consiste en l’administration d’agents chélateurs, ce qui ne résulte cependant pas en une guérison complète de la maladie. La transplantation orthotopique du foie est le seul traitement définitif actuellement, avec tous les désavantages qu’elle comporte. Un traitement alternatif à cette option est donc souhaitable. Cette étude porte sur la faisabilité de la transplantation d’hépatocytes chez le modèle animal de la maladie de Wilson, le rat Long Evans Cinnamon (LEC), avec pour buts d’en déterminer la sécurité et l’efficacité tant sur le plan clinique (amélioration de la survie, prévention de l’hépatite) que pathologique. Douze rats LEC ont reçu une injection intrasplénique de 2,6 x 105 – 3,6 x 107 hépatocytes prélevés chez des rats donneurs de souche LE. Ils ont été suivis durant 6 mois puis sacrifiés. Ils ont ensuite été comparés à un groupe contrôle de douze autres rats LEC. Aucune différence significative n’a été notée au niveau du poids, du bilan hépatique et des concentrations de cuivre biliaire et hépatique. Cependant, une amélioration de l’activité oxydase de la céruloplasmine post-transplantation a été démontrée chez le groupe de rats transplantés (49,6 ± 31,5 versus 8,9 ± 11,7). Les rats transplantés ont aussi eu une amélioration sur tous les critères histologiques étudiés. Enfin, l’ARNm de l’atp7b a été retrouvé chez 58% des rats transplantés avec un taux d’expression de 11,9% ± 13,6 par rapport à un rat LE normal. L’immunohistochimie a quant à elle démontré la présence de l’atp7b chez tous les rats transplantés. Les résultats obtenus sont considérés favorables à ce traitement alternatif, et indiquent que la transplantation d’hépatocytes est une technique sécuritaire qui peut contribuer à renverser le processus pathologique en cours dans la maladie de Wilson.