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Biomedical subjects

M Sans

Publications and source records attributed to M Sans.

At least 37 records · Page 2Linked to original sources
PubMed2000

Comparison of heparin and steroids in the treatment of moderate and severe ulcerative colitis.

BACKGROUND & AIMS: Unfractionated heparin has been found to reduce symptoms and improve healing as adjuvant therapy in patients with ulcerative colitis. The current study evaluated the efficacy and safety of unfractionated heparin in the treatment of ulcerative colitis in comparison with methylprednisolone. METHODS: A multicenter randomized trial with blinded endpoint evaluation was conducted in patients hospitalized for moderate or severe ulcerative colitis. Patients were randomized to receive heparin as a continuous infusion or methylprednisolone (0.75-1 mg x kg(-1) x day(-1)). RESULTS: Twenty-five patients entered the study: 13 received methylprednisolone and 12 received heparin. By day 10, 69% of patients in the methylprednisolone group, but none in the heparin group, achieved significant improvement or remission. C-reactive protein levels significantly decreased in the methylprednisolone group but not in the heparin group. Three patients in the heparin group were withdrawn before day 10 because of an adverse event: rectal bleeding needing transfusion (2 cases) or surgery (1 case). The proportion of patients with persistent rectal bleeding at day 10 was 31% in the methylprednisolone group and 90% in the heparin group (P<0.05). CONCLUSIONS: Unfractionated heparin as monotherapy is not effective in the treatment of moderate or severe ulcerative colitis and is associated with significant bleeding complications.

Adult↗
PubMed2000

Heparin attenuates TNF-alpha induced inflammatory response through a CD11b dependent mechanism.

BACKGROUND: In addition to its anticoagulant properties, heparin has anti-inflammatory effects, the molecular and mechanistic bases of which are incompletely defined. AIMS: The current studies were designed to test the hypothesis that heparin abrogates the expression or function of leucocyte-endothelial adherence molecules which are fundamental to the acute inflammatory response. METHODS: The effects of heparin on tumour necrosis factor alpha (TNF-alpha) induced leucocyte rolling, adhesion, and migration as well as vascular permeability were assessed in rat mesenteric venules using intravital microscopy. Expression of adhesion molecules was quantitated using a double radiolabelled monoclonal antibody (mAb) binding technique in vivo (P-selectin, intercellular cell adhesion molecule type 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1)) or flow cytometry (CD11a, CD11b, and L-selectin). Ex vivo binding of heparin to neutrophils was assessed by flow cytometry. RESULTS: TNF-alpha induced a significant increase in leucocyte rolling, adhesion, and migration, and vascular permeability, coincident with a significant increase in expression of P-selectin, ICAM-1, and VCAM-1. Ex vivo assessment of blood neutrophils showed significant upregulation of CD11a and CD11b and significant downregulation of L-selectin within five hours of TNF-alpha administration. Heparin pretreatment significantly attenuated leucocyte rolling, adhesion, and migration but did not affect expression of cell adhesion molecules or vascular permeability elicited by TNF-alpha administration. Binding of heparin was significantly increased on blood neutrophils obtained five hours after TNF-alpha administration. Preincubation with an anti-CD11b mAb but not with an anti-CD11a or anti-L-selectin antibody significantly diminished heparin binding ex vivo. CONCLUSIONS: Our results support the concept that the anti-inflammatory effects of heparin involve attenuation of a CD11b dependent adherent mechanism.

Animals↗
PubMed2000

Admixture studies in Latin America: from the 20th to the 21st century.

The present study is a review of admixture studies in Latin America, an interesting subject because of the unique history of the area, in which populations from 3 different origins had contact and intercrossed. The most often used methods of analysis of admixture in Latin America and some problems related to them, such as the determination of the parental populations and selection of genetic markers, are briefly reviewed. Several sources of data for admixture studies (surnames, quantitative traits, proteins, and molecular information) are summarized. The results obtained using protein systems and blood groups, the most often used markers in Latin America, are considered. They are classified according to their application in 3 groups of populations: urban centers, native Americans, and African-descended subjects. The data show that almost every population is dihybrid or trihybrid, and when African influence is not detected, it is probably due more to the method than to an absence of that contribution. A special section is dedicated to the direction of gene flow, and results about directional mating based on mtDNA, Y-chromosome, and nuclear DNA or proteins are also given. From these studies it is possible to conclude that Amerindian admixture came mainly from female lineages, but it is difficult to establish what happened with the African contribution. A last subject considered is the relation between interethnic crosses and diseases; it is easy to analyze that relation when the pathological condition is related to a unique allele, but when complex diseases are considered, the results are not as clear because of the influence of nongenetic factors. Finally, the perspectives for admixture studies in the 21st century are considered, and some attempts to predict their future in Latin America are made.

Africa↗
PubMed1999

VCAM-1 and ICAM-1 mediate leukocyte-endothelial cell adhesion in rat experimental colitis.

BACKGROUND & AIMS: The molecular mechanisms responsible for leukocyte recruitment in experimental colitis are poorly understood. The aims of this study were to measure expression of endothelial intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) and to determine their role in leukocyte recruitment in experimental colitis. METHODS: Rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis and control rats were studied 1, 7, or 21 days after treatment. ICAM-1 and VCAM-1 expressions were measured by the double radiolabeled antibody technique. Leukocyte-endothelial cell interactions were determined in colonic venules by fluorescence intravital microscopy. Therapeutic effects of treatment with anti-VCAM-1 antibodies were also assessed. RESULTS: Colonic endothelial ICAM-1 was constitutively expressed and did not increase in colitic animals. In contrast, constitutive expression of VCAM-1 was low but markedly increased (6-fold) 1 and 7 days after induction of colitis. Increased colonic expression of VCAM-1 paralleled macroscopic damage score, myeloperoxidase activity, and increased leukocyte adhesion in colonic venules. The latter was significantly decreased by immunoneutralization of ICAM-1 and completely abrogated by immunoneutralization of VCAM-1. Long-term administration of anti-VCAM-1 antibody resulted in significant attenuation of colitis. CONCLUSIONS: Induction of colitis in rats by TNBS is followed by up-regulation of endothelial VCAM-1. VCAM-1 and constitutive ICAM-1 are major determinants of leukocyte recruitment to the inflamed intestine.

Animals↗
PubMed1999

Prospective assessment of the risk of bacteremia in cirrhotic patients undergoing lower intestinal endoscopy.

BACKGROUND: Patients who have prosthetic heart valves, previous history of endocarditis, and surgically constructed systemic-pulmonary shunts or conduits should receive prophylactic antibiotics before colonoscopy. The usefulness of this approach in cirrhotic patients remains unknown. The present study prospectively assesses the incidence of bacteremia in these patients. METHODS: Lower intestinal endoscopy was performed in 58 cirrhotic patients. Two blood samples were obtained from every patient (just before endoscopy and within 5 minutes of withdrawal of the endoscope) and were incubated for 7 days and examined daily for growth of bacteria. Patients were closely monitored for 72 hours after endoscopy to detect the development of infectious complications. RESULTS: Only 6 cultures from 6 patients were positive. Four were obtained post-endoscopy and the remaining 2 before colonoscopy but the corresponding post-endoscopy samples were negative. All organisms recovered were normal skin flora. All patients, including those with positive cultures, remained asymptomatic during the 72 hours after the procedure. CONCLUSIONS: Our findings indicate that lower intestinal endoscopy does not induce bacteremia in cirrhotic patients with or without ascites in the absence of gastrointestinal bleeding and do not support the routine use of prophylactic antibiotics in these patients.

Bacteremia↗
PubMed1999

Prognostic factors in nonresectable pancreatic adenocarcinoma: a rationale to design therapeutic trials.

OBJECTIVE: Most patients with pancreatic cancer show an advanced tumor at the time of diagnosis. In recent years, new therapies have been developed in such patients, thus forcing the analysis of factors that influence their survival. The present study was aimed at determining the prognostic factors in a series of 134 consecutive patients with pancreatic carcinoma not suitable for surgical resection, due to either locally advanced tumors or metastatic spread. METHODS: First, 34 epidemiological, clinical, analytical, and tumor-related parameters recruited at admission were included in a univariate analysis of survival by using the Kaplan-Meier method. Those significant variables in the previous step were thereafter introduced in a Cox regression procedure. A prognostic index for calculating the relative risk of death of each patient was also proposed. RESULTS: The median survival time in the whole series was 3.11 months, the 3, 6, and 12 months probability of survival being 51%, 28%, and 8%, respectively. Eight of 34 variables (jaundice and toxic syndrome at admission, serum cholesterol, iron and alanine aminotransferase concentrations, leukocyte count, baseline performance status, and the presence of distant metastases) were selected in the univariate analysis. Of these eight parameters, the Cox regression analysis identified a preserved baseline performance status (OR = 2.14, 95% CI = 1.49-3.04) and the absence of metastases (OR = 1.34, 95% CI = 1.03-1.73) as the only variables independently associated with a longer survival. Therefore, a prognostic index was constructed allowing the division of patients in three different groups according to their relative risk of death (RRD) = exp (performance status x 0.7589 + presence of metastases x 0.2891). CONCLUSIONS: The results of the present investigation suggest that baseline performance status and distant metastases should be considered in designing and evaluating any therapeutic trial in patients with nonresectable pancreatic carcinoma.

Adenocarcinoma↗
PubMed1998

[Usefulness of ultrasonography and computerized tomography in predicting resectability of pancreatic carcinoma].

BACKGROUND: Surgical resection is the only curative treatment of pancreatic carcinoma (PC). An accurate assessment of the extension of PC is mandatory to select appropriate patients to this therapeutic option. This study was aimed at assessing the usefulness of abdominal ultrasonography (US) and computed tomography (CT) to establish tumoral staging and to predict tumor resectability. PATIENTS AND METHODS: Between January 1990 and December 1995, 84 PC patients were submitted to surgical procedures (potentially curative resection in 30%, biliodigestive anastomosis in 51% and exploratory laparotomy in 13%). Preoperative staging was carried out by means of abdominal US and/or CT. Definitive staging was established according to surgical findings, using the TNM classification. RESULTS: Accuracy of preoperative evaluation with regard to tumoral staging was 65%, being underestimated in 29 (35%) patients. This underestimation was mainly due to lesions in stage I. In addition, preoperative staging predicted tumor unresectability with a 50% sensitivity and a 83% specificity. CONCLUSIONS: US and CT have a good specificity in the staging and unresectability prediction of pancreatic cancer. However, their usefulness is limited by their low sensitivity.

Aged↗
PubMed1998

Usefulness of laparoscopy with liver biopsy in the assessment of liver involvement at diagnosis of Hodgkin's and non-Hodgkin's lymphomas.

BACKGROUND: Staging of lymphoma at diagnosis determines therapeutic strategy and disease prognosis. Hepatic involvement, demonstrated by laparotomy or laparoscopy, is frequent in Hodgkin's and non-Hodgkin's lymphoma. However, it is unclear whether these procedures are still necessary or whether they should be replaced by less invasive techniques. METHODS: Laparoscopy-assisted liver biopsies, as well as laboratory studies, bone marrow biopsy, and thoracic and abdominal computed tomography, were performed as an initial staging evaluation in 112 consecutive patients who were diagnosed with Hodgkin's or non-Hodgkin's lymphoma. RESULTS: Hepatic lymphomatous involvement was demonstrated in 18 patients (16%). It was more frequent in non-Hodgkin's (24%) than in Hodgkin's (8%) lymphomas (p < 0.04) and among stage III and IV (24%) than stage I and 11 (10%) patients (p < 0.05). The laparoscopic finding of white spots or nodules on the liver surface had a 100% specificity in the diagnosis of lymphomatous liver involvement. Conversely, hepatomegaly on both laparoscopy and computed tomography, as well as laboratory studies, had a low sensitivity and specificity. CONCLUSIONS: Laparoscopy-assisted liver biopsy was a useful technique to establish hepatic lymphomatous involvement, which was not identified by either computed tomography or laboratory studies.

Adolescent↗
PubMed1998

Effects of steroid treatment on activation of nuclear factor kappaB in patients with inflammatory bowel disease.

Nuclear factor kappB (NFkappaB) is a transcription factor that controls several genes important for immunity and inflammation. The aim of this study was to assess if activation of NFkappaB plays a role in the pathogenesis of inflammatory bowel disease (IBD), and whether steroid treatment affects NFkappaB activation. Activation of NFkappaB was analysed in colon biopsy samples of 13 patients with active IBD (8 Crohn's colitis, 5 ulcerative colitis) by electrophoretic mobility-shift assays, under basal conditions and 3 weeks after treatment with 0.75 mg kg(-1) day(-1) prednisolone. The presence of interleukin-8 mRNA in biopsies was assessed by RT-PCR. A specific NFkappaB band was present in all nuclear extracts from inflamed mucosa, whereas the band was barely detectable in uninflamed colonic mucosa. NFkappaB bands were super-shifted by antibodies against p50 subunit, whereas antibodies against p65, p52, c-Rel, or Rel B did not modify the mobility of the band. Increased interleukin-8 mRNA was detected at the same sites of NFkappaB activation. Steroid-induced healing of colonic inflammation was associated with disappearance of NFkappaB from nuclear extracts. These results support the notion that NFkappaB plays an important role in the pathogenesis of IBD, and that blockade of NFkappaB activation is one of the mechanisms by which steroids suppress the inflammatory cascade in IBD.

Adult↗
PubMed1998

Characteristics of perisinusoidal collagenization in liver cirrhosis: computer-assisted quantitative analysis.

OBJECTIVE: To determine the respective roles of septal fibrosis, necroinflammatory activity, iron deposition, steatosis, and patterns of nodular and septal remodeling in the collagenization of the perisinusoidal space in livers from patients undergoing transplantation for alcoholic or posthepatitis C cirrhosis and to ascertain whether perisinusoidal collagenization has clinical implications added to those of septal fibrosis. STUDY DESIGN: Sixty-six hepatectomy specimens from patients undergoing liver transplantation for cirrhosis were analyzed. Thirty-two alcoholic and 34 posthepatitis C cirrhoses were included. Picro Sirius-stained slides were examined with polarized light and the amount of perisinusoidal collagenization measured by computerized image analysis. Size distributions of septa and nodules were assessed by mathematical morphology methods. RESULTS: The septal and perisinusoidal fibrosis indices and Knodell and Pugh-Child scores showed significant differences between alcoholic and posthepatitis cirrhoses. Correlation between septal fibrosis and perisinusoidal collagenization was weak, though significant. Both variables correlated significantly with the clinical score. The correlation was negative between septal fibrosis or perisinusoidal collagenization and the Knodell score. CONCLUSION: Perisinusoidal collagenization was not a feature of all cases of cirrhosis, although it was more prominent in alcoholics. For the whole series, it significantly correlated with the clinical score, which increased significantly when high perisinusoidal collagenization was added to high septal fibrosis. No absolute dependence was found between perisinusoidal collagenization and septal fibrosis; percentage of slender fibrous septa and amount of iron deposition were other factors entered in the regression equation.

Adult↗
PubMed1998

Image analysis of dermal collagen changes during skin aging.

OBJECTIVE: To determine progressive quantitative, directional and textural changes in dermal collagen as a function of age and sex and to estimate their evolutive trend with appropriate regression models. STUDY DESIGN: Ninety-six samples of abdominal skin from autopsy cases were analyzed. The ages ranged from 3.5 months to 86 years. Picro-Sirius-stained slides were examined by polarizing microscopy, and spatial density, directional features and texture of collagen were measured by computerized image analysis. Nonlinear regression models were built to estimate evolutive changes with respect to age. The relationship between spatial orientation of collagen bundles and age was best modeled by linear regression. RESULTS: The evolutive patterns of dermal thickness and spatial density of collagen bundles correspond to a second-order polynomial model with a progressive increase from childhood to middle age and a relatively sharp decrease after the seventh decade. The evolution of textural pattern of dermal collagen, defined by gradient analysis, depicts a sort of inverted U. Its complexity is maximum in the first year of life, decreases until the period 25-50 years and increases progressively after the sixth decade. The horizontal orientation of collagen bundles with intermingled fascicles oriented in other directions, shown by young individuals, is progressively simplified with aging. In elderly subjects, collagen bundles have a horizontal orientation. No significant sex-related differences were found. CONCLUSION: Dermal collagen changes related to aging are apparently independent of sex, at least in abdominal skin, and show characteristic curvilinear evolutive trends defined by decreased dermal thickness in the elderly, decrease in the spatial density of collagen bundles and increase in textural heterogeneity of the dermis. Progressive simplification in the orientation of collagen bundles leading to a predominant horizontal disposition followed a linear trend. These changes could contribute to providing a substantial morphologic basis to age-associated biomechanical alterations in the skin.

Abdomen↗
PubMed1998

[Simultaneous presentation of autoimmune thyroiditis and celiac disease in an adult].

Celiac disease may be associated with other underlying autoimmune diseases. Among these, thyroid disease has been described in around 10% of the cases with hypothyroidism being the most frequently reported. Clinical suspicion of thyroid involvement in patients with celiac disease is difficult since the symptomatology is scarce or is masked by the picture of malabsorption. Nonetheless, its detection is important since it is not solved by gluten free diet and its correction requires specific treatment. Thyroid function studies, in addition to determination of antithyroglobulin and antimicrosomal antibodies, should be considered in celiac patients refractory to conventional dietetic treatment. We herein present the case of a 65-year-old woman who consulted for a malabsorption syndrome in whom celiac disease of the adult was simultaneously presented with hyperthyroidism secondary to autoimmune thyroiditis.

Aged↗
PubMed1997

Liver transplantation in patients with Caroli's disease and recurrent cholangitis.

Caroli's disease is an uncommon congenital disorder of the intrahepatic biliary tree. It is characterized by multiple and segmental dilatations of the bile ducts. The clinical course of Caroli's disease is often complicated by recurrent episodes of bacterial cholangitis that seriously impair the patient's quality of life. Despite wide spectrum antimicrobial agents, medical treatment of cholangitis is frequently unsuccessful in patients with Caroli's disease due to the persistence of bacteria in dilatated bile ducts. Other therapies, including internal or external biliary drainages and various surgical or endoscopic procedures, have been used in the treatment of Caroli's disease, with poor results. There are no previous reports in the literature of liver transplantation for recurrent cholangitis in patients with Caroli's disease. We present two such cases, in which cholangitis is resolved.

Adult↗
PubMed1997

Hepatitis G virus infection in fulminant hepatic failure.

BACKGROUND: RNA sequences of the recently identified hepatitis GB virus C (HGBV-C), also named hepatitis G virus (HGV), have been detected in patients with idiopathic fulminant hepatic failure (FHF) but the role of this agent in the disease remains controversial. AIMS: To investigate the presence and implications of HGV infection in a large series of Spanish patients with FHF. PATIENTS: Sixty eight patients with FHF, including 19 with idiopathic disease, were studied. In 28 cases, studies were performed before and after liver transplantation. For comparison 200 volunteer blood donors and 22 patients transplanted for chronic liver disease were also studied. METHODS: HGV RNA was measured in serum by reverse transcriptase polymerase chain reaction of the 5' non-coding region. RESULTS: Evidence of HGV infection was found in 3% (6/200) of blood donors and in 19% (13/68) of patients with FHF. HGV infection was more frequent in patients with hepatitis B (24%, 6/25) or hepatitis D (42%, 5/12), than in patients with idiopathic disease (11%, 2/19). Half of the patients with HGV infection used illicit intravenous drugs. Specific clinical features associated with HGV infection were not identified. A very high rate of infection with HGV was observed in patients who underwent liver transplantation, either for FHF (60%, 15/24) or chronic liver disease (45%, 9/20). CONCLUSIONS: In our geographical area, HGV infection is relatively frequent in FHF, but it does not seem to play a major role in idiopathic cases.

Adult↗