Safe and effective application of anti-TNF-alpha in a patient infected with HIV and concomitant Crohn's disease.
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Biomedical subjects
Publications and source records attributed to M Hoyos.
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HYPOTHESIS AND OBJECTIVES: the hypothesis of this study is that genes involved in the regulation of the immune system, expressed by HLA antigens and anti-neutrophil cytoplasmic antibodies (ANCA), could be determinants of disease susceptibility and behavior in inflammatory bowel disease (IBD). MATERIAL AND METHOD: seventy patients with a diagnosis of inflammatory bowel disease, 46 with ulcerative colitis and 24 with Crohn"s disease were included. HLA class I (A and B) and II (DR) antigens were studied by serological techniques. Detection of ANCA was carried out in all patients by an indirect immunofluorescence method. The relative frequencies of HLA antigens were compared with a control group made up of 156 blood donors. The control group for the ANCA study was made up of 100 individuals. RESULTS: we found a significant increased frequency of HLA-DR2 in patients with ulcerative colitis. No significant differences were found between patients with Crohn"s disease and controls regarding HLA typing. We detected a significant increase of HLA-DR3 in extensive forms of ulcerative colitis. Detection of ANCA was positive in 46% of the patients with ulcerative colitis and in 12% of the patients with Crohn"s disease (p <0.05). We observed an increased frequency of ANCA in patients with UC and HLA-DR2 (p = 0.15). CONCLUSIONS: the association found between HLA-DR3 and extensive forms of ulcerative colitis provides evidence of genetic heterogeneity. The relationship between ANCA and HLA phenotype (although not significant) supports this concept.
BACKGROUND: Two clearly differentiated evolutive patterns of Crohn's disease, obstructive and fistulizing, exist, but the early clinical parameters which can predict the evolution are unknown. AIM: To evaluate whether clinical variables, present at the time of diagnosis, may help in predicting a subsequent evolutive behaviour. PATIENTS AND METHODS: Ninety out of 140 evaluable patients were included. After a median of 50.2 months since diagnosis, 64 patients (71%) followed an obstructive pattern while 26 patients (28.9%) had a fistulizing form. Clinical variables were analysed as predictors of outcome. Logistic regression was carried out in order to obtain a mathematical model that would predict the evolution. The individual ability of the mathematical model to predict evolution was assessed using relative receiver operating characteristic (ROC) curves. RESULTS: The variables which were retained in the model were duration of disease before diagnosis (DD), onset of symptoms (OS), presence of anal disease (AD) and the presence of abdominal mass (AM). The equation z = -9.49 + 2.2643 (AD) - 0.0066 (DD) + 2.5282 (AM) + 1.3433 (OS) was obtained. The probability of evolution towards an obstructive form was P = 1/(1 + e(-Z)). This model can predict 96.88% of obstructive forms but only 53.85% of fistulizing forms. The mathematical point section (ROC curve) corresponds to a probability of 45.2%. Considering an obstructive pattern when the probabilities are above this point, the sensitivity is 98% and the specificity is 50%. CONCLUSIONS: The prediction of an obstructive pattern is feasible using simple clinical variables. The mathematical model obtained is useful for predicting this but not the fistulizing pattern.
Advantages of the continuous magnetic flow sorting for biomedical applications over current, batch-wise magnetic separations include high throughput and a potential for scale-up operations. A continuous magnetic sorting process has been developed based on the quadrupole magnetic field centered on an annular flow channel. The performance of the sorter has been described using the conceptual framework of split-flow thin (SPLITT) fractionation, a derivative of field-flow fractionation (FFF). To eliminate the variability inherent in working with a heterogenous cell population, we developed a set of monodisperse magnetic microspheres of a characteristic magnetization, and a magnetophoretic mobility, similar to those of the cells labeled with a magnetic colloid. The theory of the magnetic sorting process has been tested by injecting a suspension of the magnetic beads into the carrier fluid flowing through the sorter and by comparing the theoretical and experimental recovery versus total flow-rate profiles. The position of the recovery maxima along the total flow-rate axis was a function of the average bead magnetophoretic mobility and the magnetic field intensity. The theory has correctly predicted the position of the peak maxima on the total flow-rate axis and the dependence on the bead mobility and the field intensity, but has not correctly predicted the peak heights. The differences between the calculated and the measured peak heights were a function of the total flow-rate through the system, indicating a fluid-mechanical origin of the deviations from the theory (such as expected of the lift force effects in the system). The well-controlled elution studies using the monodisperse magnetic beads, and the SPLITT theory, provided us with a firm basis for the future sorter evaluation using cell mixtures.
The purpose of this study was to investigate the effect of melatonin, at pharmacological doses, on serum lipids of rats fed with a hypercholesterolemic diet. Therefore, different groups of animals were fed with either the regular Sanders Chow diet or a diet enriched in cholesterol. Moreover, animals were treated with or without melatonin in the drinking water for 3 months. We show that melatonin treatment did not affect the levels of cholesterol or triglycerides in rats fed with a regular diet. However, the increase in total cholesterol and low-density lipoprotein (LDL)-cholesterol induced by a cholesterol-enriched diet was reduced significantly by melatonin administration. On the other hand, melatonin administration prevented the decrease in high-density lipoprotein (HDL)-cholesterol induced by the same diet. No differences in the levels of very low-density lipoprotein (VLDL)-cholesterol and triglycerides were found. We also found that melatonin administration slightly decreased serum uric, bilirubin and increased serum glucose levels. Other biochemical parameters, including total proteins, creatinine, urea, phosphorus, calcium, glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), gamma-glutamyltranspeptidase (gamma-GT), acetyl cholinesterase (AcCho), and alkaline phosphatase (ALP) were not modified by melatonin treatment. Finally, lipid peroxidation (LPO) was studied in membranes of liver, brain, spleen, and heart as an index of membrane oxidative damage. Results show that hypercholesterolemic diet did not modify the LPO status in any of the tissues studied. However, chronic melatonin administration significantly decreased LPO. Results confirm that melatonin participates in the regulation of cholesterol metabolism and in the prevention of oxidative damage to membranes.
Free bowel perforation is a relatively infrequent complication of Crohn's disease. It may present during the evolution of the disease or, occasionally, in the onset of the same and may involve the small intestine or colon. We herein present 4 cases, three of ileal localization and one of colonic localization. In one of the 3 former cases and the latter case perforation took place prior to diagnosis of the disease. Review of the literature was performed with respect to the frequency, pathogenesis and characteristics of this complication and the importance of determined diagnostic techniques such as echography and CAT in addition to the most adequate treatment are commented upon.
We have studied prospectively 126 consecutive patients recruited with a known diagnosis of ulcerative colitis (UC; n = 78) and Crohn's disease (CD; n = 48) for anti-neutrophil cytoplasmatic antibodies (ANCA) by indirect immunofluorescence (IFI). Forty-six percent of UC and 18% of CD patients were found positive. The sensitivity and specificity for UC diagnosis were 0.46 and 0.81, respectively. We evaluated the pattern of IFI exhibited (perinuclear: pANCA and cytoplasmatic: cANCA). cANCA was found in 77% of CD and in only 30% of UC patients (p = 0.01). Sera from all CD patients were positive at a 1:20 dilution (and not at higher dilution) and it occurred in only in 14 UC patients (30%). Positive sera were also tested to characterize the antigen specificity by enzyme-linked immunosorbent assay (ELISA) but the antigenic nature of ANCA could not be identified in most cases. No differences were found between ANCA positive and ANCA negative patients regarding colonic extension (UC) or colonic involvement (CD), activity and colectomy. We conclude that ANCA may be a helpful diagnostic test in UC patients but it not seems to be important as a marker of activity. ANCA positivity can reflect disease heterogeneity in UC patients, perhaps discriminating those with immunologic disturbances.
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UNLABELLED: The effects of smoking on the onset and clinical course of inflammatory bowel disease (IBD) have been widely debated. Although smoking appears to have a clearly unfavorable effect on the course in Crohn's Disease (CD), the relationship between smoking and localization of the disease is less clear. AIM: To evaluate, in our group of patients, the relationship between smoking and the development of ulcerative colitis (UC) or CD, and between smoking and the localization of CD in the large bowel or in other sites. PATIENTS AND METHODS: The smoking habits of 171 patients at the time of diagnosis were assessed with a questionnaire. Subjects were classified into three subgroups as smokers, nonsmokers and ex-smokers. Current smokers were grouped according to their level of consumption as those who smoked fewer than or more than 10 cigarettes per day. A total of 161 patients were studied (UC n = 69, CD n = 92). Patients with CD were divided into those with colonic disease and those with no colonic involvement. We evaluated the relationship between smoking and the form of IBD, localization (colonic or noncolonic) and the presence of perianal disease (PAD) in CD. The results were analyzed with the chi-squared test. RESULTS: Smoking was more frequent in patients with CD than in those with UC (72.8% vs 31.9%). Among patients with CD, more patients without colonic involvement were smokers (84.6% vs 64.2%). However, among patients with CD involving the colon, smoking was significantly more common (64.2%) than among patients who had UC (31.9%). CONCLUSIONS: Our findings confirm a relationship between smoking and CD. Smoking seems to be associated with some degree of protection of the colonic mucosa, especially in heavy smokers.
OBJECTIVE: To assess the prevalence of familial occurrence in patients with inflammatory bowel disease and to evaluate the differences among groups of patients with and without familial history. PATIENTS AND METHODS: Complete information about sex, age of onset of inflammatory bowel disease, initial location, extracolonic manifestations and perianal disease (in Crohn's disease) was obtained from 187 patients, 99 with Crohn's disease, and 88 with ulcerative colitis. RESULTS: In 9 patients (9%) with Crohn's disease and 11 (12.5%) with ulcerative colitis, at least one first-degree relative also had inflammatory bowel disease. Three relatives of patients with Crohn's disease had ulcerative colitis and no relative of patients with ulcerative colitis had Crohn's disease. As compared with the group of patients with ulcerative colitis and no familial history, patients with familial history had more frequently distal location and extra-colonic manifestations. No differences were observed among patients with Crohn's disease and familial or non familial history. CONCLUSIONS: Prevalence of inflammatory bowel disease in relatives of patients with Crohn's disease or ulcerative colitis is increased. In ulcerative colitis, it is possible to segregate two different groups according to familial history.
BACKGROUND: Left ventricular hypertrophy (LVH) is one of the physiopathological effects of hypertension and one of the main risk factors for sudden death, myocardial infarction and congestive heart failure. Drugs to treat hypertension must not only reduce blood pressure, but also modify the facts which lead to ventricular hypertrophy. This study has been designed to assess the effect of amlodipine, a calcium-antagonist, on LVH in hypertensive patients. METHODS: 20 hypertensive patients (mild to moderate, both sexes, mean age 45.0 yr) were included in a single-blind study. After an initial, four weeks placebo period, active treatment was given (amlodipine 5 mg a day). Dose titration was made after 4-8 weeks to 10 mg a day if necessary and continued until the end of the study. Systolic (SBP) and diastolic blood pressure (DBP), as well as pulse rate (PR) and adverse events were recorded at every visit. Blood and urine analysis, catecholamine, plasmatic renin activity and Mode M echocardiography were made at the beginning and the end of the study. RESULTS: Only one patient was excluded. SBP and DBP showed a significantly fall (p < 0.001). In 80% of patients DBP fell under 90 mm Hg. Every echocardiographic parameter, but left ventricular diastolic dimension, showed significantly reductions at the end of the study: septum thickness (p = 0.001), posterior wall thickness (p = 0.001), left ventricular systolic dimension (p = 0.014), wall relative thickness (p = 0.015), shortening fraction (p = 0.009), left ventricular mass (p = 0.001) and corrected left ventricular mass (p = 0.001). Blood parameters did not modify. CONCLUSIONS: Amlodipine has a beneficial effect on LVH and also is an effective and safe drug to treat mild to moderate hypertension.
OBJECTIVE: To assess the efficacy of 6-mercaptopurine in I.B.D. treatment. PATIENTS: 21 patients with chronic active disease (8 patients with ulcerative colitis and 13 with Crohn's disease) and mean follow-up 5 years for both diseases (range ulcerative colitis 1-11 and Crohn's disease 1-14 years, respectively). The indications of inmunosuppressor treatment were: corticosteroid dependence (3 ulcerative colitis; 6 Crohn's disease), refractory disease (5 ulcerative colitis; 4 Crohn's disease), fistulae (5 Crohn's disease) and perianal disease (4 Crohn's disease). All patients received a mean dose of 30 mg/day of prednisone. Complete, partial and clinical remission, of failure of treatment are defined. RESULTS: The mean dose of 6-mercaptopurine was 90 mg/day with a response mean time of 3.4 months and 12 months of duration (range 1-36). Complete or partial clinical remission was achieved in 77.7% of all the patients (steroid dependent 88.8%, refractory disease 77.7%, fistulae 40%, perianal disease 100% of all the patients (steroid dependent 88.8%, refractory disease 77.7%, fistulae 40%, perianal disease 100%), in 87% of ulcerative colitis patients (steroid dependent 100%, refractory 80%) and in 61.5% of Crohn's disease patients (steroid dependent 83.7%, refractory disease 75%). Secondary effects were observed in two patients. CONCLUSIONS: Our results suggest that 6-mercaptopurine is an effective and safe drug in the treatment of patients with ulcerative colitis and Crohn's disease in corticosteroid dependent, refractory and perianal disease, its efficacy being less in fistulae.
A stratified random sample of 464 persons aged 40 to 79 years, drawn from enumeration registers in the Bridgetown area of Barbados, participated in this survey. The prevalence of hypertension (defined as systolic blood pressure of at least 160 mm Hg, diastolic blood pressure of at least 95 mm Hg, or use of antihypertensive medication) was 47% and 43% for women and men, respectively. Diabetes was present in 17% of all subjects (18% of women and 15% of men). Of the 209 hypertensive subjects, 82% were aware of their blood pressure status. The proportion of previously diagnosed hypertensive subjects on medication was 72% for men and 68% for women. Fifty-three percent of men and 42% of women were overweight (body mass indices [weight in kilograms divided by height in meters squared] between 25 and 30). However, 30% of women and 10% of men were obese (body mass indices over 30), supporting the growing recognition of the marked gender disparity in obesity among persons of African origin in the Caribbean. Body mass index was positively associated with hypertension (OR = 1.33; 95% CI: 1.1-1.6). Obese persons experienced a 2.6 times greater risk of hypertension compared to those with body mass indices below 25. Similar statistically significant associations were observed between diabetes and body mass index: OR comparing body mass index over 30 with body mass index under 25 was 2.5 (95% CI: 1.3-5.1) for all subjects, 1.0 (0.3-4.1) for men only, and 5.2 (1.9-14) for women only. Preventing obesity in this population could reduce the incidence of hypertension and diabetes by approximately 30% and 33% among men and women, respectively.
In this study we investigated the effect of selective (M1) and non-selective (M1 and M2) pharmacologic blockade of muscarinic receptors on cholecystokinin-induced gallbladder emptying. After validating the method of study, the gallbladder function was evaluated in 15 normal volunteers by quantitative biliary scintigraphy, and the effect of intravenous atropine (0.15 mg/10 kg) and pirenzepine (10 mg) was analyzed in each subject. Atropine significantly reduced the ejection period and the ejection fraction of gallbladder evacuation. Pirenzepine reduced the ejection period, but the ejection fraction remained unchanged. We conclude that the effect of cholecystokinin on gallbladder motility is mediated through muscarinic receptors. Our results suggest that M2 receptors, but not M1 receptors, are involved in this response.
A knowledge, attitudes, beliefs, and practices (KABP) survey was performed among Barbadian secondary schoolchildren 11-16 years old in January 1990. The survey sought to assess the children's knowledge of AIDS and human immunodeficiency virus (HIV) transmission; their attitudes toward people with HIV/AIDS; their sexual practices; and changes needed in education programs seeking to reduce childhood HIV transmission. A pretested self-administered questionnaire was used. The survey sample was derived by selecting every eleventh student on the rosters of all the secondary schools in Barbados. All of the survey respondents completed the questionnaire on the same day, having been assembled examination-style for that purpose. The results showed high levels of correct knowledge about the principal routes of HIV transmission. However, a considerable proportion of the respondents harbored incorrect beliefs regarding mosquito transmission and dangers to blood donors, and many showed uncertainty or incorrect knowledge regarding possible HIV transmission by biting, spitting, or use of public toilets. About a third of the children (51.4% of the boys and 18.7% of the girls) said they had experienced sexual intercourse, though only 20% reported being sexually active in the year preceding the survey. Three-quarters of the sexually experienced group said they knew how to use condoms, but only a third said there was any time when they had used protection during sexual intercourse. Overall, the results indicate that education efforts prior to the survey had been effective, but that reinforcement of such efforts as well as their extension into the primary schools is warranted. Further research directed at helping these efforts to encourage more meaningful changes in sexual behavior is also needed.
BACKGROUND: There is no satisfactory treatment for refractory ascites in patients with cirrhosis. Both peritoneovenous shunts and paracentesis have been used, but there is uncertainty about their relative merits. METHODS: We studied 89 patients with cirrhosis and refractory ascites who were randomly assigned to receive either repeated large-volume paracentesis plus intravenous albumin or a LeVeen peritoneovenous shunt. Patients in the paracentesis group in whom recurrent tense ascites developed during follow-up were treated with paracentesis, and those in the peritoneovenous-shunt group with diuretic agents or by the insertion of a new shunt if there was shunt obstruction. RESULTS: During the first hospitalization, ascites was removed in all 41 patients in the paracentesis group and in 44 of the 48 patients in the peritoneovenous-shunt group. The mean (+/- SD) duration of hospitalization in the two groups was 11 +/- 5 and 19 +/- 9 days, respectively (P less than 0.01). There were no significant differences in the number of patients who had complications or died. During follow-up, 37 patients in each group were hospitalized again. In the paracentesis group, the number of rehospitalizations for any reason (174 vs. 97 in the peritoneovenous-shunt group) or for ascites (125 vs. 38) was significantly higher, and the median time to a first readmission for any reason (1 +/- 1 vs. 2 +/- 2 months) or for ascites (2 +/- 2 vs. 8 +/- 17 months) was significantly shorter than in the peritoneovenous-shunt group. The total times in the hospital during follow-up, however, were similar in the two groups (48 +/- 49 and 44 +/- 39 days, respectively). Three patients had obstructions of their peritoneovenous shunts during their first hospitalizations, and 15 patients had a total of 20 obstructions during follow-up. Survival was similar in both groups. CONCLUSIONS: The LeVeen shunt and paracentesis are equally effective in relieving refractory ascites. The former may provide better long-term control of ascites, but shunt occlusion is common and survival is not improved.
In 15 patients with duodenal diverticula close to the papilla of Vater we evaluated the motor activity of the sphincter of Oddi by endoscopic biliary manometry. Both basal pressure and phasic activity were similar to those in nine patients without biliopancreatic disease and in 60 patients with common bile duct stones. The anatomical relationship between the papilla and diverticula did not lead to any change in the motor pattern. If juxtapapillary diverticula are associated with a higher prevalence of biliopancreatic disease, dysfunction of the sphincter of Oddi does not seem to play a pathogenic role.
The relationship between donor status for antibody to hepatitis B core antigen and the occurrence of non-A, non-B posttransfusion hepatitis in the recipient was prospectively studied in 112 patients undergoing open-heart surgery who were followed for 6.5 months after surgery. Non-A, non-B posttransfusion hepatitis occurred in five (7.93%) of 63 patients who had received at least one anti-HBc-positive blood unit compared to seven (14.28%) of 49 patients who received anti-HBc-negative blood only. Statistical analysis revealed that the incidence of non-A, non-B posttransfusion hepatitis was independent of the use of blood positive for anti-HBc. Based upon these results and the high prevalence (17.3%) of anti-HBc among our blood donor population, the exclusion of anti-HBc-positive blood does not seem appropriate to achieve a reduction in the incidence of non-A, non-B posttransfusion hepatitis.