Improvement of autoimmune hepatitis during pregnancy followed by flare-up after delivery

OBJECTIVES: Pregnancy in autoimmune hepatitis has been a rare event, but it has become more frequent with improved therapy. The present study aimed to analyze the consequences for mother and child in patients with autoimmune hepatitis. METHODS: Fourteen pregnancies have been followed in five patients with autoimmune chronic hepatitis (AIH) and in one with autoimmune sclerosing cholangitis (overlap AIH-PSC). RESULTS: Features of AIH improved markedly from the second trimester of pregnancy onward, allowing a decrease in immunosuppressive therapy. After delivery (or stillbirth in one patient), the activity of the autoimmune disease flared up rapidly in 12 of 14 events. CONCLUSIONS: Pregnancy induces a state of immune tolerance with improvement of the liver tests in AIH. This could result from a transition of TH1 to TH2 predominance during pregnancy. A flare-up often occurs after delivery. Preemptive increase of the immunosuppressive therapy is therefore advocated consecutive to delivery. Azathioprine use seems to be safe during pregnancy.     

The incidence of recurrent venous thromboembolism in carriers of factor V Leiden is related to concomitant thrombophilic disorders

The duration of anticoagulant treatment after a first episode of venous thromboembolism primarily depends on the risk of recurrence. Variability of recurrence rates in factor (F) V Leiden carriers may be due to concomitant thrombophilic disorders. A retrospective study was performed in 329 FV Leiden carriers with a history of venous thromboembolism (262 probands, 67 relatives). The annual rate of first recurrence was estimated in relatives. The contribution of concomitant thrombophilic disorders to the recurrence rate was evaluated in probands and relatives by a nested case--control analysis in 105 matched pairs of carriers either with or without recurrence. The overall annual recurrence rate was 2.3 per 100 patient-years. The adjusted risk of recurrence for concomitant thrombophilic disorders was: 9.1 (1.3-62.8) for the FII mutation; 1.0 (0.2-4.9) for homozygosity for FV Leiden; 1.5 (0.2-9.5) for inherited deficiencies of protein C or S; 1.8 (0.7-4.9) for FVIII coagulant activity (FVIII:C) levels >122%; 5.4 (1.6-18.6) for fasting homocysteine levels >15.2 micromol/l; and 4.4 (1.0-18.7) for loading homocysteine levels >45.8 micromol/l. Of these disorders, only the FII mutation and hyperhomocysteinaemia significantly increased the risk of recurrence in FV Leiden carriers. The estimated recurrence rate ranged from 0.45 per 100 patient--years after a secondary first event in the absence of concomitant disorders to 4.8 per 100 patient-years when a spontaneous first event was combined with concomitant disorders. Our study provides supportive evidence that the incidence of recurrent venous thromboembolism in heterozygous FV Leiden carriers depends on the concomitance of other thrombophilic disorders, in addition to whether the first thrombotic event occurred spontaneously.     

Complete genome sequence, taxonomic assignment, and comparative analysis of the untranslated regions of the Modoc virus, a flavivirus with no known vector

We recently developed a model for flavivirus infection in mice and hamsters using the Modoc virus (MODV), a flavivirus with no known vector (P. Leyssen, A. Van Lommel, C. Drosten, H. Schmitz, E. De Clercq, and J. Neyts, 2001, Virology 279, 27-37). We now present the coding and noncoding sequence of MODV. The Modoc virus genome was determined to be 10,600 nucleotides in length with a single open reading frame extending from nucleotides 110 to 10,234, encoding 3374 amino acids. The deduced gene order of the single open reading frame is C-prM-E-NS1-NS2A-NS2B-NS3-NS4A-NS4B-NS5, which is exactly the same as that of the mosquito- and tick-borne flaviviruses. It is flanked by a 5'- and 3'-untranslated region (UTR) of 109 and 366 nucleotides, respectively. Alignment of the MODV amino acid sequence with that of 20 other flaviviruses revealed several regions with high sequence similarity corresponding to functionally important domains (e.g., the serine protease/helicase/NTPase of NS3 and the methyltransferase/RNA-dependent RNA polymerase of NS5) and conserved sites for proteolytic cleavage by viral and cellular proteases. Phylogenetic analysis of the entire coding region confirmed the classification of MODV within the flaviviruses with no known vector, which is in agreement with previous findings based on partial NS5 sequences. A detailed comparative analysis of the putative folding patterns of the 5'- and 3'-UTR of MODV and of the tick- and mosquito-borne viruses was carried out. Structural elements in the 5'- and 3' UTR of MODV that are preserved among vector-borne flaviviruses were noted and so were structural elements distinguishing the MODV UTRs from mosquito-borne and tick-borne flaviviruses. Also the putative secondary structure of circularized MODV RNA is presented.     

A custom template and definitive prosthesis allowing immediate implant loading in the maxilla: a clinical report

PURPOSE: The purpose of the present investigation was to examine to what extent precision data from 3-dimensional planning software for oral implants can be transferred to the operative field by means of a drilling template, containing high-precision drilling sleeves, fitted on the jawbone. It was investigated whether this procedure would allow advance preparation of a fixed definitive prosthesis that could be placed at the completion of surgery. MATERIALS AND METHODS: This procedure was experimentally carried out in 2 cadavers and later in 8 consecutive human patients. RESULTS: The results indicated a nearly perfect match between the positions and axes of the placed implants and those planned. DISCUSSION: This procedure permitted the placement of a definitive fixed prosthesis with limited freedom of space between the abutments and the metallic cylinders incorporated into the prosthesis. CONCLUSION: These encouraging results of the Leuven information technology-based oral rehabilitation by means of implants (LITORIM) are presently being further investigated at the clinical level.     

The role of whole blood viscosity in premature coronary artery disease in women

BACKGROUND: Impaired hemorheology has been demonstrated in atherosclerotic disease and has shown a relationship with classical risk factors. Blood viscosity (eta), being the ratio of shear stress over shear rate, is an important parameter of hemorheology. In women with premature coronary artery disease (CAD), the underlying risk factors are a matter of debate and the role of whole blood viscosity in its pathogenesis has not been documented. AIM: To investigate the association of whole blood viscosity with premature CAD in women, with complaints suggestive of angina pectoris. METHODS: Eighty-eight women (mean age 53 years) were divided into two groups, those with a high likelihood of CAD (LIKELI+) and those with a low likelihood of CAD (LIKELI-), based on medical history and technical investigations. Assessment of risk factors comprised smoking, diabetes mellitus, arterial hypertension, left ventricular hypertrophy (LVH), systolic and diastolic blood pressures, total low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol, triglycerides, body mass index, menopause, hormone replacement therapy, uric acid and creatinine, and predicted 10-year cardiovascular risk according to the Framingham study was calculated. Whole blood viscosity was determined at 37 degrees C using a rotational cone-and-plate viscosimeter. RESULTS: Baseline characteristics did not differ significantly between the groups except for antiplatelet therapy (P=0.001), prevalence of diabetes mellitus (P=0.002), predicted 10-year cardiovascular risk (P=0.007), essential hypertension (P=0.02), LVH (P=0.03) and smoking habits (P=0.04). LIKELI+ women had a significantly higher whole blood viscosity at all shear rates compared with LIKELI- women (P<0.05). All blood viscosities measured from 25 to 125 s(-1) were highly significantly (P<0.0001) correlated with eta(250s(-1)). Univariate correlates with eta(250s(-1)) comprised triglycerides (P=0.006) and haematocrit (P=0.026). Binary logistic multivariate regression analysis for high likelihood of CAD revealed that only presence of arterial hypertension (P<0.0001) was predictive. Multiple regression analysis demonstrated that haematocrit (P=0.001) and likelihood of CAD (P=0.01) were the only significant determinants of eta(250s(-1)). CONCLUSION: In this study, blood viscosity did not appear as an independent risk factor for the prediction of premature CAD in women. Viscosity may act as a marker of CAD or of classical risk factors.     

Prevention of Staphylococcus aureus biofilm on dialysis catheters and adherence to human cells

BACKGROUND: Dialysis patients, often carriers of Staphylococcus aureus in their nares, are at high risk of S. aureus infections. METHODS: We examined whether RNAIII inhibiting peptide (RIP), which interferes with quorum sensing mechanisms, reduces adherence of S. aureus to host cells and to dialysis catheter polymers in vitro. Adherence was tested by spectroscopy using safranin staining, by confocal scanning laser microscopy and by atomic force microscopy. RESULTS: RIP inhibited bacterial adherence to HaCat and HEp-2 cells and reduced adherence and biofilm formation not only on polystyrene, but also on both polyurethane- and silicone-made dialysis catheters, with a preponderant effect on silicone, to which bacteria were more adherent. CONCLUSION: RIP opens a new perspective in anti-S. aureus prophylaxis, particularly in dialysis patients.     

Endotoxin impairs endothelium-dependent vasodilation more in the coronary and renal arteries than in other arteries of the rat

Endotoxemia may result in endothelial dysfunction, and some vascular beds may be affected more than others. To test this hypothesis, we studied, in vitro, the reactivity of isolated rat coronary, renal, superior mesenteric, and hepatic arteries exposed to endotoxin (E. coli, 50 microg. mL(-1)) or saline for 2 h at 37 degrees C. Vascular smooth muscle function was tested using 125 mM KCl, the vasoconstrictors norepinephrine (NE), and the thromboxane analog U46619 (coronary artery). Endothelium-dependent vasorelaxation was tested with acetylcholine (ACh) in preconstricted vessels. Although differing between vessel types, the smooth muscle contractile responses were not affected by endotoxin, either in the presence or absence of L-arginine. Endotoxin impaired the response to ACh in rat coronary arteries (92.7 +/- 4.6% vasodilation in control and 41.3 +/- 11.6% in endotoxin-exposed segments) and in renal arteries (66.7 +/- 5.2% vasodilation in control and 43.2 +/- 4.9% in endotoxin-exposed segments), so that there was a mean 55% decrease vs controls in coronary and a mean 35% decrease in renal arteries. Endotoxin did not affect superior mesenteric and hepatic arteries. Brief endotoxin exposure of isolated rat arteries may thus inactivate endothelial NO synthase, independent of iNOS. The increase in heterogeneity among endothelium-dependent vasodilation after endotoxin may help to explain early blood flow maldistribution in endotoxin shock.     

Influence of intraluminal thrombus on structural and cellular composition of abdominal aortic aneurysm wall

INTRODUCTION: It has been suggested that the intraluminal thrombus of abdominal aortic aneurysm (AAA) affects the underlying vessel wall. Aneurysm enlargement has been associated with growth of thrombus, and rupture has been proposed to occur after bleeding into the thrombus. To examine how thrombus affects the vessel wall, we compared the morphology of aneurysm wall covered with thrombus with wall segments exposed to flowing blood.Material and methods Sixteen patients (14 men, 2 women; age range, 56-79 years) undergoing elective repair of AAA, where computed tomography scans showed thrombus and segments of the aneurysm wall exposed to flowing blood, were included in the study. Specimens from the aneurysm were taken for light and electron microscopy. Masson trichrome staining was performed for wall thickness determination and demonstration of collagen, and Weigert-van Gieson staining for elastin. The cellular composition was analyzed by immunohistochemistry with antibodies against CD3 for T cells, CD4 for T helper cells, CD8 for T cytotoxic cells, CD20 for B cells, CD68 for macrophages, and smooth muscle alpha-actin for smooth muscle cells (SMCs). Caspase-3 staining and TUNEL analysis were performed to evaluate apoptosis. RESULTS: The aneurysm wall covered with thrombus was thinner and contained fewer elastin fibers, and the few that were found were often fragmented. This part of the wall also contained fewer SMCs and more apoptotic nuclei than the wall exposed to flowing blood. Clusters of inflammatory cells were detected in the media of the aneurysm wall and in higher numbers in the parts covered with thrombus. Electron microscopy showed that the aneurysm wall without thrombus contained a dense collagenous matrix with differentiated SMCs. In the segment covered with thrombus, SMCs were more dedifferentiated (synthetic) and apoptotic or necrotic. There were also an increased number of inflammatory cells located in close contact with SMCs in various stages of apoptosis. CONCLUSION: The aneurysm wall covered with thrombus is thinner and shows more frequent signs of inflammation, apoptosis of SMCs, and degraded extracellular matrix. These findings suggest that thrombus formation and accumulation of inflammatory cells may perturb the structural integrity and stability of the vessel wall and thereby increase the risk for aneurysm rupture.     

Metabolism of salbutamol differs between asthmatic patients and healthy volunteers

Patients with asthma are a target group for medication with beta2-agonists, often in combination with corticosteroids. Salbutamol is commonly marketed as racemate. R-Salbutamol carries beta2-agonistic property whereas S-salbutamol does not. The racemate undergoes stereoselective sulphatisation by sulfotransferases mainly in the gut and liver, so that S-salbutamol rests for a longer time in the body and reaches higher plasma levels than R-salbutamol. Ten patients with mild stable asthma and at present without cortisone medication were given racemic salbutamol as ventoline 4 mg orally. Plasma and urine levels were estimated until 24 hr after ingestion. For comparison healthy volunteers were treated in the same way. The group of asthma patients was then treated with budesonide inhalations 800 microg daily for one week and the initial programme resumed. Non-cortisone-treated asthmatic patients displayed higher levels of both R- and S-salbutamol in plasma than did healthy volunteers after one single ingestion of racemic salbutamol (CMAX both comparisons P<0.05). Plasma levels of salbutamol isomers in cortisone-treated asthmatic patients resembled the levels in volunteers. The most plausible explanation for the discrepancy in values between asthmatic patients and volunteers is a defective metabolic function by asthmatic patients possibly enzymatic in origin.