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Biomedical subjects

P Fickert

Publications and source records attributed to P Fickert.

26 records · Page 2Linked to original sources

Mycophenolate mofetil in patients with Crohn's disease.

OBJECTIVE: Intolerance to azathioprine is a rare but important problem in treating chronically active Crohn's disease. We performed this study to evaluate mycophenolate mofetil as an alternative immunosuppressive therapy for patients with Crohn's disease who did not tolerate azathioprine. METHODS: Four patients with highly active perianal Crohn's disease and two patients with chronically active, steroid-dependent Crohn's disease were included. All patients consumed 2 g/day of mycophenolate mofetil for a median of 8 months (range, 6-12 months). Disease activity was measured by the Perianal Crohn's Disease Activity Index in patients with perianal disease and by the Crohn's Disease Activity Index in patients with chronically active Crohn's disease. RESULTS: Azathioprine-induced side effects disappeared after the drug was discontinued. All patients improved during treatment with mycophenolate mofetil, as shown by a remarkable reduction in the respective clinical scores. Five patients showed no side effects during treatment with mycophenolate mofetil. After 4 months' treatment one patient developed diarrhea that was probably not due to mycophenolate mofetil. CONCLUSION: Mycophenolate mofetil could be an alternative therapy to azathioprine in patients with Crohn's disease.

Adult↗

Sonographic evaluation of focal nodular hyperplasias (FNH) of the liver with a transpulmonary galactose-based contrast agent (Levovist).

Focal nodular hyperplasias (FNH) are hypervascular, benign focal liver lesions. Differentiation of FNH from other focal liver lesions is of clinical importance. The purpose of this study was to examine the impact of a new, transpulmonary echo-enhancing agent SHU 508A (Levovist) and recent Doppler techniques in the sonographic evaluation of FNH. 43 patients with 61 focal nodular hyperplasias of the liver were examined with grey scale ultrasound and power Doppler ultrasound. Levovist, a galactose-air-microbubble suspension was administered intravenously in all patients, either by bolus injection (400 mg ml-1) or continuous pump-infusion (300 mg ml-1). Visualization of the feeding vessels and vascularity of the lesions were evaluated. The resistance indexes (RI) in the feeding vessel and the hepatic artery were assessed and compared with the diameters of the FNH. The mean diameter of FNH was 4.3 cm (+/- 1.0). Echo enhanced power Doppler ultrasound was superior to unenhanced power Doppler ultrasound in the detection of the feeding artery (85% vs. 98%) in FNH and depicted the internal vascular architecture more clearly, especially in lesions located in the left lobe of the liver. Lesions smaller than 3 cm did not show a characteristic vascular architecture with echo enhanced Doppler ultrasound. The resistance index of the feeding artery (mean: 0.51 +/- 0.08) is significantly (p < 0.0001) lower than that of the hepatic artery (mean 0.65 +/- 0.06) with a mean difference of -0.14 +/- 0.01 in the same patient. The RI of the feeding artery significantly decreased as the size of the FNH increased, whereas RI differences between the hepatic artery and the feeding artery increased with lesion size. Intravenous (i.v.) bolus injection of the contrast agent will depict the hypervascular nature of FNH more clearly than i.v. infusion, although the latter will significantly prolong the diagnostic window. In conclusion, i.v. infusion of Levovist improves the visualization of the feeding artery and the radiating vascular architecture in FNH located in the left lobe of the liver due to improved signal-to-noise ratio and results in more effective suppression of motion artefacts. Although echo enhanced Doppler ultrasound improves the detection of the low resistance arterial feeding vessel in small FNH, it will not, however, reveal a specific vascular pattern in these lesions.

Adult↗

Nitric oxide-dependent and -independent vascular hyporeactivity in mesenteric arteries of portal hypertensive rats.

1. Increased production of nitric oxide (NO) has been suggested to underlie both the vascular hyporeactivity to vasoconstrictors and the splanchnic vasodilatation seen in portal hypertension. This study assessed the role of NO in the vasoconstrictor hyporeactivity of portal vein-ligated (PVL) rats in isolated and in situ perfused mesenteric arterial beds. 2. Isolated perfused mesenteric arteries of PVL rats were significantly less reactive to noradrenaline (NA), methoxamine (METH), arginine vasopressin (AVP) and endothelin-1 (ET-1) than those from sham-operated (Sham) rats. 3. Blockade of NO synthesis with NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) in isolated perfused mesenteric arteries from PVL rats restored the reactivity to bolus injections of AVP and ET-1, but had little effect on the hyporeactivity to NA or METH. Cyclo-oxygenase inhibition with indomethacin (5 microM) likewise did not restore reactivity to METH of isolated perfused mesenteric arteries of PVL rats. 4. The hyporeactivity to METH seen in isolated perfused mesenteric arteries from PVL rats was reduced by low concentrations of AVP (20 nM) or ET-1 (1 nM) which per se caused only a slight increase in perfusion pressure. When L-NAME (100 microM) was combined with AVP (20 nM) or ET-1 (1 nM), respectively, reactivity to METH of isolated perfused mesenteric arteries of PVL rats was restored to the level seen in Sham rats. These effects of AVP and ET-1 were not mimicked by precontracting the vessels with 5-hydroxytryptamine (5 microM). 5. The differential effects of L-NAME and AVP on the hyporesponsiveness to methoxamine and AVP were corroborated by experiments performed with the in situ perfused mesenteric vascular bed preparation. 6. These data indicate that both NO-dependent and NO-dependent mechanisms are involved in the vasoconstrictor hyporesponsiveness of mesenteric arteries from portal hypertensive rats. The hyporeactivity to AVP and ET-1 is mediated by NO whereas the reduced responsiveness to adrenoceptor agonists appears to be predominantly NO-independent AVP and ET-1, in addition, seem to inhibit the NO-independent mechanism of vascular hyporeactivity, since the hyporesponsiveness to METH was reduced in the presence of AVP or ET-1 and abolished by the combination of these peptides with L-NAME.

Animals↗

Combination of cyclosporine, azathioprine and prednisolone for perianal fistulas in Crohn's disease.

OBJECTIVES: Fistulas in Crohn's disease remain a difficult clinical challenge. Rapid improvement with cyclosporine followed by deterioration after discontinuation of this drug has been reported. This study aimed to determine whether fast remission and long-term improvement could be achieved when cyclosporine was administered concurrently with azathioprine and low-dose prednisolone and then be discontinued. METHODS: Nine patients with fistulas were enrolled in this open study. For the first two weeks cyclosporine was administered intravenously at a dose of 5 mg/kg/day. Azathioprine and low-dose prednisolone were also given during this period. After two weeks cyclosporine was administered orally for a further ten weeks while azathioprine and a tapered dose of prednisolone were continued. Effectiveness was evaluated clinically, by a scoring system and by magnetic resonance imaging. RESULTS: With intravenous cyclosporine as part of this regimen, all nine patients went into remission within days. There were no recurrences after changing from intravenous to oral cyclosporine. Cyclosporine was terminated after three months while azathioprine and low-dose prednisolone were continued. Thereafter, four patients did not deteriorate, three deteriorated slightly, and two patients had a recurrence. The CDAI (Crohn's Disease Activity Index) improved from 200 (range 85-350) to 136 (range 26-200) by the end of the third month. Serological markers remained stable after discontinuation of cyclosporine. There were no serious side effects during this triple drug regimen. CONCLUSIONS: The combination of cyclosporine, azathioprine and low-dose prednisolone leads to marked improvement of perianal fistulas in Crohn's disease. Remission occurs quickly under cyclosporine. These remissions can be maintained with azathioprine in a majority of patients.

Adult↗

Acute Budd-Chiari syndrome with fulminant hepatic failure in a pregnant woman with factor V Leiden mutation.

Budd-Chiari syndrome during pregnancy has rarely been reported. This report presents a case of acute hepatic failure in a 20-year-old pregnant woman attributable to Budd-Chiari syndrome with underlying resistance to activated protein C caused by factor V Leiden mutation. The patient delivered a healthy girl by cesarean section in the 31st week of pregnancy. Acute hepatic failure in the 6th week postpartum was successfully treated by emergency liver transplantation, and the patient and her child were doing well at 8-month follow-up. Liver transplantation was lifesaving; normal factor V production by the transplant corrected the underlying coagulopathy. In this patient, latent thrombophilia attributable to activated protein C resistance was apparently aggravated by the hypercoagulable state of pregnancy leading to acute Budd-Chiari syndrome. Activated protein C resistance should be sought as an etiologic factor in patients with Budd-Chiari syndrome.

Adult↗

Increased carbohydrate-deficient transferrin during pregnancy: relation to sex hormones.

Controversy exists whether carbohydrate-deficient transferrin (CDT) is valuable as a screening tool for fetal alcohol syndrome. We evaluated serum CDT in 60 non-alcohol-abusing women at different stages of normal pregnancy. CDT was weakly related to week of pregnancy and to human placental lactogen. CDT did not correlate with iron oestradiol or progesterone. By contrast, good correlations were found between transferrin and week of pregnancy or either sex hormone. Using multiple linear regression analysis, only transferrin and week of pregnancy were important predictors of CDT. The diagnostic accuracy of CDT for detecting alcohol abuse may be limited in pregnant women and should be carefully assessed in relation to alcohol consumption.

Estradiol↗

Evaluation of molecular parameters for routine assessment of viremia in patients with chronic hepatitis C who are undergoing antiviral therapy.

OBJECTIVE: To define the usefulness of molecular parameters in patients with chronic hepatitis C who are undergoing antiviral therapy. Anti-hepatitis C virus (HCV) treatment was monitored by determination of serum HCV load and by presence of HCV RNA in peripheral blood mononuclear cells (PBMCs). STUDY DESIGN/METHODS: Fifty-one patients with chronic hepatitis C undergoing antiviral therapy with interferon-alpha plus ribavirin were studied. Serum HCV RNA load was tested with a quantitative assay (Amplicor HCV Monitor Test) before, during, and up to 12 months after end of treatment. If HCV RNA was not detectable, serum samples were subsequently tested with a qualitative assay (Cobas Amplicor HCV Test) and corresponding ethylenediaminetetraacetic acid (EDTA)-treated blood was checked for presence of HCV RNA in peripheral blood mononuclear cells (PBMCs). Sustained virologic response was defined by loss of HCV RNA 12 months after the end of treatment. RESULTS: Four patients (7.8%) were found to be sustained virologic responders, 17 (33.3%) were transient virologic responders, and 30 (58.8%) were virologic nonresponders. No significant difference was found in the median pretreatment serum HCV RNA load between sustained virologic responders, transient virologic responders, and virologic nonresponders. At 1 month after start of therapy, HCV RNA was not detectable with both the serum and the PBMC assay in 12 (23.5%) of 51 patients. Four remained HCV RNA-negative until 12 months after the end of treatment. In 14 of 17 transient virologic responders, reappearance of HCV RNA was detected earlier in PBMCs than in serum. CONCLUSIONS: Based on these results in 51 patients, quantitation of baseline serum HCV RNA does not appear to be a decisive factor to the management of the individual patient. Early assessment of serum HCV RNA level after start of anti-viral treatment seems to be of major importance to identify virologic nonresponders. Reappearance of HCV RNA may be demonstrated earlier in PBMCs than in serum.

Adult↗