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Biomedical subjects

J Fevery

Publications and source records attributed to J Fevery.

At least 37 records · Page 2Linked to original sources

Bilirubin-IXbeta is a marker of meconium, like zinc coproporphyrin.

BACKGROUND: Because meconium accumulates continuously in the fetal intestine, analysis of the postnatally excreted material could yield important information of intrauterine metabolism and maturation. Therefore, a study of the bilirubin pigments in meconium and in the first neonatal stools was carried out. METHODS: Meconium and stools from 37 neonates of various gestational ages were collected carefully, and stored at -20 degrees C, protected by aluminium foil. Samples were defrosted, vortex mixed with an equal amount of dimethyl sulfoxide, centrifuged, and submitted to analysis by high-pressure liquid chromatography using newly developed methods to identify and to quantitate the bilirubin-IXalpha, -IXbeta, -IXgamma, and -IXdelta isomers. In addition, samples were also submitted to diazo coupling with ethyl anthranilate. Total coproporphyrins and zinc coproporphyrin were assayed for comparison. RESULTS: Unconjugated bilirubin-IXalpha and -IXbeta were detected in meconium but not the -IXgamma or the -IXbeta isomer. Bilirubin-IXbeta was the predominant pigment and comprised 63% to 96% of the unconjugated bilirubins in the first sample of meconium excreted. Its amount decreased rapidly during the first 5 days in full-term newborns, but this occurred more slowly in preterm neonates, especially in those with a gestational age less than 30 weeks. The decrease of bilirubin-IXbeta over time correlated with that of coproporphyrin. CONCLUSIONS: Bilirubin-IXbeta is the prevailing bile pigment in the first excreted sample of meconium. It gradually decreases after birth and can be considered a biochemical marker of meconium, like zinc coproporphyrin.

Bile Acids and Salts↗

Screening properties of questionnaires and laboratory tests for the detection of alcohol abuse or dependence in a general practice population.

BACKGROUND: Early identification of alcohol abuse or dependence is important in general practice because many diseases are influenced by alcohol. General practitioners, however, fail to recognise most patients with alcohol problems. AIM: To assess the diagnostic performance of the CAGE and AUDIT questionnaires, their derivatives, and laboratory tests in screening for alcohol abuse or dependence in a primary care population (male and female patients), attending their general practitioner (GP). DESIGN OF STUDY: A diagnostic cross-sectional study. SETTING: A random sample of patients who were over 18 years of age (n = 1992) attending 69 general practices situated in the same region in Belgium. METHOD: Alcohol questionnaires (CIDI 1.1, section I, CAGE, AUDIT, AUDIT-C, Five-Shot, and AUDIT Piccinelli) were completed, demographic information was recorded, and patients underwent conventional blood tests, including mean corpuscular volume, liver function tests, the gamma-glutamyl transferase test, and carbohydrate-deficient transferrin (CDT, estimated using %CDT). Calculations of sensitivity, specificity, positive predictive value, negative predictive value, odds ratios with their 95% CIs, and receiver operating characteristic (ROC) curves for different scores of the questionnaires and laboratory tests, using DSM-III-R as the reference standard. RESULTS: The past-year prevalence of alcohol abuse or dependence in this population was 8.9% (178/1992) of which there were 132 male and 45 female patients attending a general practice. The GPs identified 33.5% of patients with alcohol abuse or dependence. Among male patients, all questionnaires had reasonable sensitivities between 68% and 93% and hence at lower cut-points than recommended. Only the sensitivity of the CAGE, even at its lowest cut-point of > or = 1 was lower (62%). In female patients the sensitivities were lower; however, odds ratios were higher for different questionnaires. The receiver operating characteristic (ROC) curves did not differ between the questionnaires. The laboratory tests had low diagnostic accuracy with areas under the ROC curves (AUCs) between 0.60 and 0.67 for female patients and 0.57 and 0.65 for male patients. CONCLUSIONS: This is one of the largest known studies on alcohol abuse or dependence among family care practices. We confirm earlier results that the AUDIT questionnaire seems equally appropriate for males and females; however, screening properties among male patients are higher. Nevertheless, the Five-Shot questionnaire is shorter and easier to use in a general practice setting and has nearly the same diagnostic properties in male and female general practice patient populations. We confirm that conventional laboratory tests are of no use for detecting alcohol abuse or dependence in a primary care setting. Also, the %CDT cannot been used as a screening instrument in this general practice population.

Alcoholism↗

A phase I/II study of recombinant human interleukin-12 in patients with chronic hepatitis B.

BACKGROUND/AIMS: Interleukin-12 (IL-12) may be active against hepatitis B virus (HBV). The objective of the study was to assess the tolerability, activity, pharmacokinetics, and pharmacodynamics of three dose levels (0.03 microg/kg b.w., n=15; 0.25 microg/kg b.w., n=15; 0.50 microg/kg b.w., n=16) of recombinant human (rHu) IL-12 given s.c. once a week for 12 consecutive weeks. METHODS: Forty-six patients with chronic hepatitis B, HBV DNA positivity and aminotransferase elevation were included in a multicenter prospective randomized phase I/II study. RESULTS: Compared with the baseline, HBV DNA levels had decreased significantly at the end of rHuIL-12 treatment and after the 12-week follow-up period (p<0.001). The response to rHuIL-12 treatment was dose-dependent: at the end of the study HBV DNA clearance was greater in patients treated with 0.50 microg/kg b.w. (25%) or with 0.25 microg/kg b.w. (13%) compared with those given 0.03 microg/kg b.w. (7%). Moreover, HBeAg became undetectable at the end of follow-up in five of the patients given the 0.25microg/kg (2/15) or the 0.50 microg/kg (3/16) dose. The drug pharmacology showed that IL-12 had an estimated half-life of 30 h with levels remaining detectable for more than 48 h after rHuIL-12 administration. The serum levels of IL-12, interferon-gamma, IL-10, neopterin and beta2-microglobulin as well as the area under the curve (AUC) were rHuIL-12 dose-related. Side effects were observed more frequently with higher doses, including moderate decreases in lymphocyte and neutrophil counts; three patients withdrew prematurely from treatment. The local reaction observed at the injection site was unrelated to the drug dose. Only one patient showed detectable antibody levels to rHuIL-12 without clinical impact. CONCLUSIONS: Treatment with rHuIL-12 at the doses investigated is safe and tolerable, and appears to be active against HBV in patients with chronic hepatitis B.

Adjuvants, Immunologic↗

Pericardial disease is often not recognised as a cause of chronic severe ascites.

BACKGROUND/AIMS: Severe chronic ascites remains a difficult diagnostic and therapeutic problem. Even in the current era, constrictive pericarditis is an underestimated and sometimes unrecognised cause. Moreover, missing the diagnosis deprives patients of remedial therapy. METHODS: Two cases of calcified constrictive pericarditis, complicated with cirrhosis and diagnosed in a late stage, are described. Due to insufficient clinical appreciation and lack of trust in echocardiography results, performed by cardiologists who were insufficiently familiar with the echocardiographic features of constrictive pericarditis, diagnosis was delayed in the two patients RESULTS: The diagnosis of constrictive pericarditis as a cause of ascites is based upon the clinical signs of right heart failure in a patient with normal systolic left and right ventricular function and a high, serumascitic albumin-content difference. Complementary workup with complete Doppler echocardiography study, right and left heart catheterisation and MRI or cine CT of the heart is necessary to confirm the diagnosis. CONCLUSION: Careful history taking and clinical examination remain the cornerstone of any diagnostic work-up, even in this era of technological refinement.

Adolescent↗

Oesophageal varices: assessment of the risk of bleeding and mortality.

Patients with oesophageal varices run a high risk of bleeding and even death, however rates of bleeding and mortality vary greatly. Indeed, a number of patients with varices never bleed. Prophylactic therapy is effective, but can be associated with side-effects. It remains to be determined which patients are at high risk of bleeding and require treatment. In addition, since non-response to medical therapy has been reported to occur in 20-40% of patients, the effect of a given prophylactic drug, or combinations of drugs, needs to be tested. A review is given of available methods of assessment. The Hepatic Venous Pressure Gradient, and measurements of the variceal pressure, are two proven methods, and the latter has the advantages of being non-invasive and having value in presinusoidal portal hypertension.

Esophageal and Gastric Varices↗

Hepatic osteodystrophy: the influence of liver disease and portal hypertension on cytokine activation.

Chronic liver disease is frequently complicated by bone disease. The mechanisms leading to bone-loss are unknown but are probably not related to abnormal vitamin D metabolism. The effects of portal hypertension and porto-systemic shunting on bone-loss have not been studied. It is postulated that liver disease, or the complications of liver disease (portal hypertension or porto-systemic shunting), might be responsible for the activation of cytokines. It is further postulated that these cytokines might be the final common pathway leading to bone-loss in both parenchymal and cholestatic liver disorders by modifying osteoblast or osteoclast function.

Cytokines↗

Intestinal colonization leading to fecal urobilinoid excretion may play a role in the pathogenesis of neonatal jaundice.

BACKGROUND: Neonatal hyperbilirubinemia remains of concern because of the potential danger for the central nervous system. Because urobilinogen is a nontoxic derivative of bilirubin, the current study was conducted to examine the fecal excretion of urobilinoids and bilirubin in healthy newborns and infants, as well as their intestinal bacteria capable of reducing bilirubin, to assess a possible relation to serum bilirubin levels during the first weeks of life. METHODS: Bilirubin pigments, urobilinoids, and porphyrins were measured in stools of infants during the first week (group A, n = 60) and between the second week and the first 6 months of life (group B, n = 64). Microbiologic analysis of stools was performed in selected cases and bilirubin-converting activity of isolated bacteria was determined in vitro. RESULTS: Urobilinoids were detectable in stools of 57% of the neonates at day 5, but not before. However, fecal urobilinoid production on that day was only a fraction of that observed in adults (0.07 vs. 0.7-3.6 mg/kg per day), whereas at week 6 it increased significantly to an average of 0.9 mg/kg per day. Microbiologic analysis of neonatal stools revealed two novel bacterial strains of Clostridium perfringens and Clostridium difficile capable of reducing bilirubin to urobilinoids. CONCLUSIONS: Urobilinoids can be detected in stools of 57% of newborns at day 5 after delivery. However, the urobilinoid production during the first week of life is quantitatively insufficient to contribute significantly to the removal of bilirubin. Enhancement of the microbial conversion of bilirubin could decrease the intestinal concentration of bilirubin and may decrease the degree or enhance the removal of neonatal hyperbilirubinemia.

Bacteria↗

The value of CAGE, CUGE, and AUDIT in screening for alcohol abuse and dependence among college freshmen.

BACKGROUND: This study attempted to (1) determine the prevalence of alcohol problems in college freshmen, (2) assess the performance of both the CAGE and the Alcohol Use Disorders Identification Test (AUDIT) questionnaires in this population, and (3) assess the possibility of improving the CAGE and/or AUDIT. METHODS: A sample of 3564 consecutive college freshmen, with a mean age of 18 years, at the Catholic University of Leuven, (Belgium) completed, during a cross-sectional study, a questionnaire assessing drinking behavior and identifying students at risk as defined by DSM-IV criteria. The questionnaire also included the CAGE questionnaire and the AUDIT. Calculations of sensitivity, specificity, negative predictive value, positive predictive value, likelihood ratios, and receiver operating characteristic curves for different scores of the CAGE and the AUDIT were performed, using DSM-IV criteria as the reference standard. RESULTS: The area under the receiver operating characteristic curve of the CAGE and the AUDIT was 0.76 and 0.85, respectively. The cutoff score of 1 for the CAGE was associated with a sensitivity of 42%, a specificity of 87%, a positive predictive value of 36%, and a negative predictive value of 90%. A score of 6 or more for the AUDIT gave a sensitivity of 80%, a specificity of 78%, a positive predictive value of 37%, and a negative predictive value of 77%. These results were related with a prevalence of 14.1% of alcohol problems. Replacing one question of the CAGE by "often driving under the influence" resulted in the CUGE (acronym for "cut down, under influence, guilty feelings, and eye opener"), with an area under the curve of 0.96, a positive likelihood ratio of 8.7, and a negative likelihood ratio of 0.04. CONCLUSIONS: Prevalence of alcohol problems in college students is confirmed to be high. When screening for alcohol problems in a college freshmen population, one question seems extremely important. The newly constructed CUGE questionnaire may improve screening efforts in students, compared with existing questionnaires.

Adolescent↗

Hepatocellular carcinoma in Belgium: clinical and virological characteristics of 154 consecutive cirrhotic and non-cirrhotic patients.

OBJECTIVE: This study analyses the characteristics of patients with hepatocellular carcinoma (HCC) in a low endemic area with special emphasis on the differences between cirrhotic and non-cirrhotic patients. DESIGN AND SETTING: The files of 154 consecutive patients with HCC observed in a single tertiary care hospital have been investigated to determine epidemiological parameters and diagnostic procedures. RESULTS: Compared to non-cirrhotic cases, cirrhotic patients with HCC are older and have a more pronounced male predominance. Their disease is more advanced, they usually present with multi-focal tumours, rarely located in the left liver lobe. Antibodies to hepatitis C (anti-HCV) are present in 55%, 52% ever had contact with hepatitis B (HBV) and 31% were hepatitis B surface antigen (HBsAg)-positive. Six non-cirrhotic cases were anti-HCV-positive. alpha-Fetoprotein (AFP) elevation > 50 and > 400 microg/l was more frequently observed in cirrhotic patients with HCC (P = 0.016). A striking association was found between enhanced AFP levels and the presence of anti-HCV (P = 0.0006), while no such relation existed for AFP and HBV markers. The sensitivity of a 'routine' ultrasound examination is disappointing for the early detection of HCC in cirrhotic patients. CONCLUSIONS: In our hospital, in a low endemic area for HCC, we have a surprisingly high proportion of non-cirrhotic patients with HCC (40%). In cirrhosis, usually the consequence of alcohol abuse or hepatitis B or C, small tumours can be missed by ultrasonography if not specifically looked for. AFP levels are particularly elevated in hepatitis C-induced HCC.

Adolescent↗

Is there a difference between CAGE interviews and written CAGE questionnaires?

BACKGROUND: The CAGE questionnaire is a frequently studied and used instrument for screening of alcohol problems. It was developed and tested as a written questionnaire, but, clinically, it is often used as an oral interview. No comparisons have been made between the results of a written and an oral CAGE. This study attempted to (1) compare the results of a written CAGE questionnaire and a CAGE interview, and (2) compare the efficiency of using a simple open-ended question about drinking habits before asking the CAGE and asking the CAGE without an introduction. METHODS: All patients who attended a general internal medicine, cardiology, or hepatology clinic were classified according to the week of the consultation, as follows: group I (week 1), patients completed a written CAGE and were subsequently interviewed during a normal consultation by a physician, who also asked the CAGE questions; group II (week 2), a physician first interviewed the patients, including the CAGE, and subsequently patients completed a written CAGE; and group III (week 3), patients completed a CAGE interview after an open-ended introduction ("What do you drink during the day?"). Kappa values were used to compare the answers of the written and oral CAGE interviews (groups II and I). Nonparametric ANOVA was used to compare the results of group III and the oral interview of group II. RESULTS: Mean age was comparable between the groups, gender ratio was comparable between groups I and III, but there were fewer males in group II. Comparison of all written CAGEs with the oral CAGEs in the same patients resulted in an accuracy of 0.91 and a kappa value of 0.75 (95% CI, 0.66-0.84). No significant difference could be found between the results of the oral CAGE with or without an open-ended introduction (p = 0.46). CONCLUSIONS: We found no difference between the oral and the written versions of the CAGE. This is important because most research results originate from written questionnaires. Our results do not support the finding that a different approach to the CAGE questions results in an increasing number of patients in which alcohol problems were detected.

Adult↗

[Prevalence of alcohol abuse and alcohol dependence according to DSM-IV criteria in first year university students].

OBJECTIVE: To determine the prevalence of alcohol problems in first-year college students. DESIGN: Cross-sectional. METHOD: Data on the prevalence of alcohol abuse or dependence according to DSM-IV criteria were collected in the period November 1995-April 1996 among college freshmen at the Catholic University of Louvain (Belgium). 3564 consecutive students completed a questionnaire which assessed drinking behaviour (Composite International Diagnostic Interview CIDI, Section J) and identified students at risk as defined by DSM-IV criteria. Our study included a large number of college freshmen, so we were able to perform our analyses with a large statistical power. All students had the opportunity to refuse their co-operation, but there were no non-responders, so selection bias was absent. The medical ethical committee of the KU Leuven approved this study. RESULTS: Of all 3564 consecutive students 501 (14.1%; 95% confidence interval (95% CI): 12.9-15.3) met DSM-IV criteria of alcohol abuse (n = 373; 10.5%; 9.5-11.5) or of alcohol dependence (n = 128; 3.6%; 3.0-4.2). Of the male students 301 (18.5%; 16.7-20.5) met the criteria of alcohol abuse and 96 (5.9%; 4.8-7.1) of alcohol dependence, of the female students 72 (3.7%; 2.9-4.6) and 32 (1.6%; 1.2-2.3) respectively. More than 10% (12.2%; 11.1-13.3) of these freshmen operated a vehicle under influence. This contributed in a major way to the DSM-IV conclusion. CONCLUSION: In this, one of the first studies among college freshmen using DSM-IV criteria the prevalence of alcohol abuse was in excess of 10%. In addition a substantial proportion of college freshman appeared to be alcohol dependent according to DSM-IV criteria.

Adolescent↗

Transfection of a rat hepatoma cell line with a construct expressing human liver annexin V confers susceptibility to hepatitis B virus infection.

Previously, we have found that human liver annexin V (hA-V; in earlier reports referred as Endonexin II) is a specific hepatitis B surface antigen (HBsAg) binding protein. In this study, we demonstrate that transfection of rat hepatoma FTO 2B cells, a cell line that is not infectable by hepatitis B virus (HBV) and does not express hA-V, with a construct containing the hA-V gene, resulted in hA-V expressing cells susceptible to HBV infection. After in vitro infection, transfected FTO cells (assigned as FTO 9.1 cells) expressing hA-V in cultures were shown to contain HBV-precore/core, X mRNAs, and covalently closed circular (ccc) DNA as detected by polymerase chain reaction (PCR). The presence of HBV ccc and replicative intermediate DNA was also demonstrated by Southern blot hybridization assay. HBV DNA secreted in the culture medium was also evident as determined by quantitative branched DNA (bDNA) assay. HBsAg and hepatitis B core antigen (HBcAg) could also be detected by an immunocytochemical method in 10% to 15% of the cells at day 3 and day 5 after infection. Infectivity of in vitro-propagated HBV was demonstrated by infection of the naive FTO 9.1 cells with the culture supernatant from HBV-carrier cultures. In contrast to primary cultures of human hepatocytes and FTO 9.1 cells, primary rat and mouse hepatocytes, as well as rat hepatoma cell lines that do not express hA-V, are not susceptible to HBV infection. These findings suggest that hA-V plays a key role in the initial step of HBV infection and that the species-specific susceptibility to HBV infection and replication in hepatocytes is associated with the expression of hA-V.

Animals↗

Variceal pressure is a strong predictor of variceal haemorrhage in patients with cirrhosis as well as in patients with non-cirrhotic portal hypertension.

BACKGROUND: Variceal pressure is a strong predictor for a first variceal bleed in patients with cirrhosis. AIMS: To evaluate whether variceal pressure is also a determinant of the risk of a first variceal bleed in patients with non-cirrhotic portal hypertension. METHODS: Variceal pressure was measured non-invasively in 25 patients with non-cirrhotic portal hypertension and large varices while receiving a stable therapeutic regimen. Factors predictive of bleeding were compared with those observed in 87 cirrhotics. RESULTS: The one year incidence of variceal bleeding was 32% (n=28) for the cirrhotic and 20% (n=5) for the non-cirrhotic patients. There was no difference in factors predicting the risk of bleeding between the groups, except for variceal pressure. For the same level of variceal pressure, the risk of variceal bleeding was lower in patients with non-cirrhotic portal hypertension. Multiple logistic regression analysis revealed the following variables as having a significant predictive power: variceal pressure (p=0.0001), red spots (p=0.004), and the time interval between the first observation of the varices and the moment of variceal pressure measurement (p=0. 0046). For the non-cirrhotics the risk of bleeding increased with higher Child-Pugh score (p=0.0024); this was not the case for the cirrhotic patients (p=0.9521). CONCLUSION: Variceal pressure is a major predictor of variceal bleeding in patients with cirrhosis as well as in patients with non-cirrhotic portal hypertension. The risk of bleeding in non-cirrhotics is less than in cirrhotics for the same level of variceal pressure. In patients with non-cirrhotic portal hypertension the risk of variceal bleeding increases more with advancing disease.

Adult↗

Variceal pressure is a factor predicting the risk of a first variceal bleeding: a prospective cohort study in cirrhotic patients.

Predictive criteria for a first variceal hemorrhage lack substantial accuracy. Cross-sectional studies suggest a close relationship between variceal pressure (VP) and the occurrence of variceal bleeding. In the present prospective cohort study, the significance of VP measurement for prediction of a first variceal bleed was assessed. Eighty-seven patients with cirrhosis and large esophageal varices who had never developed variceal bleeding were followed for 12 months. The endpoint of the study was the presentation or not of a variceal hemorrhage. Thirty-four patients (39%) were in Child's class A, 37 in class B (43%), and 16 in class C (18%). The median interval between endoscopic diagnosis of varices and the beginning of the study was 15 months. Twenty-eight patients (32%) developed a variceal hemorrhage with a bleeding-related mortality of 18% (n=5). The 1-year mortality overall was 16% (n=14). Variables predictive of a first bleed identified by Cox proportional hazards regression model were: the level of VP, the North Italian Endoscopic Club (NIEC) score, and the interval between the diagnosis of varices and the start of the study. By adding VP to NIEC, a significant gain in prognostic accuracy was obtained (P = .003). In conclusion, the present study provides evidence that the level of VP is a major predictive factor for variceal hemorrhage, and that it provides further prognostic information in addition to the NIEC index.

Adult↗

Biliary cirrhosis induces type IIx/b fiber atrophy in rat diaphragm and skeletal muscle, and decreases IGF-I mRNA in the liver but not in muscle.

BACKGROUND/AIMS: Patients with cirrhosis complain of fatigue, which in part may be due to the progressive muscle atrophy, noted especially when signs of decompensation appear. In addition, weaning from mechanical ventilation may be difficult in some patients following liver transplantation. Since little is known about the peripheral muscles and the diaphragm in cirrhosis, we investigated diaphragm and gastrocnemius histochemical properties, and diaphragm contractile properties in male rats with biliary cirrhosis. In addition, the extent to which insulin-like growth factor I (IGF-I) was involved in the regulation of muscle function was also examined, since IGF-I is known to induce growth and regeneration as well as to exert a protein anabolic action. METHODS: Ten rats underwent a sham operation, while another ten underwent bile duct ligation and excision. After 5 weeks, biliary cirrhosis was confirmed histologically in random liver biopsies. RESULTS: Compared to sham animals, diaphragm mass in cirrhotic rats was decreased by 10% (p<0.05), while masses of other respiratory (e.g. scalenus medius -21%, p<0.001) or peripheral muscles (e.g. gastrocnemius -24%, p<0.0001) decreased more. No changes in diaphragm force nor in its endurance were observed between the two groups. However, a clear decrease in the cross-sectional area of type IIx/b muscle fiber was present in both diaphragm (1360+/-147 vs 1112+/-167 microm2, p<0.02) and gastrocnemius (1954+/-265 vs 2328+/-245 microm2, p<0.02). Finally, hybridization of Northern blot with a rat cDNA IGF-I probe (gift from Dr D. Leroith, Bethesda, USA) labeled with alpha-32P revealed that in cirrhotic rats, the relative expression of IGF-I was markedly reduced by 45% in the liver (p<0.05) but was unchanged in the two muscles studied. CONCLUSIONS: In this model of biliary cirrhosis: (i) muscle wasting was less pronounced in the diaphragm than in other muscles; (ii) type IIx/b fiber atrophy in respiratory (diaphragm) and peripheral muscles (gastrocnemius) developed while diaphragm contractile properties remained unchanged; and (iii) the relative expression of IGF-I was reduced in the liver only, while it remained unchanged in the muscle. The functional significance of these changes, their pathogenesis and presence in other models and in human cirrhosis remain to be elucidated.

Animals↗