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Biomedical subjects

F Nevens

Publications and source records attributed to F Nevens.

At least 37 records · Page 2Linked to original sources

Measurement of variceal pressure with an endoscopic pressure sensitive gauge: validation and effect of propranolol therapy in chronic conditions.

AIM/METHODS: Variceal pressure was measured at endoscopy in 98 patients with a non-invasive, pressure-sensitive gauge technique. RESULTS: In nine patients undergoing sclerotherapy, the values obtained correlated closely with those determined by fine-needle puncture of the varices (r = 0.95, p < 0.001). In 15 patients receiving placebo as part of a double-blind, placebo-controlled prospective evaluation of prophylactic treatment with propranolol, variceal pressure did not change significantly over a 1-year period: 16.5 +/- 3.2 mmHg at onset: 16.7 +/- 3.4 after 3 months and 15.9 +/- 3.5 after 12 months. In contrast, propranolol therapy given to 15 patients decreased the pressure from 16.2 +/- 3.0 mmHg before therapy to 13.5 +/- 2.0 after 3 months (p < 0.001) and to 13.1 +/- 4.1 after 12 months (p < 0.05). Patients with a recent bleeding episode had higher pressures than those who had not yet experienced any haemorrhage (19.3 +/- 3.5 mmHg, n = 17 vs 13.9 +/- 3.3, n = 62) (p < 0.001). This was confirmed in a prospective study: the last variceal pressure in bleeders and non-bleeders was respectively 17.2 +/- 1.7 mmHg (n = 4) and 14.8 +/- 4.1 mmHg (n = 26) (p < 0.01). Overall, variceal pressure measurements correlated with the size of varices, the presence of red colour signs and with the North Italian Endoscopic Club score. CONCLUSIONS: This study has shown that the non-invasive pressure gauge Varipress represents a reproducible method to regularly assess variceal pressure, an important parameter related to the risk of bleeding, and to assess the effects of pharmacological therapy with propranolol.

Adrenergic beta-Antagonists↗

The effect of long-term treatment with spironolactone on variceal pressure in patients with portal hypertension without ascites.

The effect of spironolactone on esophageal variceal pressure (VP) in patients without ascites was investigated. VP was assessed using a noninvasive endoscopic gauge. Spironolactone was administered during a 6-week period at a dosage of 100 mg/d. This treatment decreased VP from 16.8 +/- 1.9 (SD) to 14.1 +/- 2.7 mm Hg (P < .001) in a group of 12 patients and from 18.6 +/- 2.1 to 13.7 +/- 4.1 mm Hg (P < .01) in another group of 8 patients who still had high VP despite chronic intake of propranolol. In both groups, placebo administration to 12 and 8 comparable patients did not significantly alter VP. Spironolactone induced a significant reduction of plasma volume (42.1 +/- 5.5 to 36.1 +/- 6.6 mL/kg body weight, P < .01) and of the concentration of alpha-atrial natriuretic peptide (alpha-ANP) (39.8 +/- 22 to 27.7 +/- 20 pg/mL, P < .01); in addition, a pronounced increase in plasma renin activity (PRA) (1.1 +/- 0.9 to 7.5 +/- 3.4 ng/mL/h, P < .001) was induced by the treatment. No significant changes in systemic hemodynamics were observed during the studies. Severe side effects were not observed except for a high incidence (55%) of painful gynecomasty in the male patients. In conclusion, chronic spironolactone administration effectively lowers VP, even in patients under chronic propranolol therapy. The combination of propranolol and spironolactone deserves further study as a prophylactic therapy of variceal hemorrhage, but development of gynecomasty might be a problem. Finally, we confirmed the reproducibility of VP measurements with the noninvasive gauge in chronic conditions.

Adrenergic beta-Antagonists↗

Assessment of variceal pressure by continuous non-invasive endoscopic registration: a placebo controlled evaluation of the effect of terlipressin and octreotide.

Octreotide has been proposed for the treatment of variceal bleeding. The effects on portal pressure, however, have been variable in published studies. As bleeding is more directly related to pressure in the varices, this study investigated the effect on variceal pressure of octreotide and terlipressin, a vasoactive drug with a well established effect. Variceal pressure was measured during four to eight minutes by a continuous non-invasive endoscopic registration method. Thirty patients in whom a stable variceal pressure recording had been obtained during at least one minute, were randomised to receive either 2 mg terlipressin, 50 micrograms octreotide or an identical volume of saline, as a single intravenous injection given over 60 seconds. For the final analysis three patients had to be excluded because of lack of a satisfactory recording. There were no significant clinical differences between the three groups of patients. Placebo administration did not induce significant changes, but a mean decrease in variceal pressure of -27% was noted with terlipressin, starting from two minutes onwards. Variceal pressure changes after injection of octreotide were variable and the mean change in pressure did not reach statistical significance. Seven of 10 patients showed a temporary increase in variceal pressure. In conclusion, terlipressin induces a significant and progressive decrease in variceal pressure but inconsistent variations of variceal pressure changes were seen after octreotide administration. This is probably related to its effect on central venous pressure. This study also shows that continuous variceal pressure recording with the non-invasive endoscopic registration technique detects in an accurate way the effect of vasoactive drugs on variceal pressure, because placebo injection did not produce significant changes.

Adult↗

Non-invasive variceal pressure measurements: validation and clinical implications.

Recently, it has become clear that the best way to reduce the mortality related to a variceal bleeding is to prevent it. Since however not all patients will bled, a way to predict a variceal hemorrhage is therefore urgently needed. The current endoscopic scores for the prediction of variceal bleeding are based on rather subjective markers. The present experimental work added the measured variceal pressure to this scoring systems, but a large number of patients should prospectively be evaluated to allow development of a model based on numerical data. Medical treatment of variceal bleeding, both to prevent and to stop the bleeding, became the treatment of choice for the majority of our cirrhotic patients. Our present investigations demonstrated that the non-invasive measurement of variceal pressure with the endoscopic gauge represent a reliable technique to assess the effect of drug treatment for portal hypertension both in acute and chronic conditions. Non invasive variceal pressure measurement may play therefore a crucial role in the future care of patients with chronic liver disease and portal hypertension. Developments with regard to primary or secondary prevention of bleeding will depend on further insight to be gained in the pathogenesis of the development of varices in a variety of experimental models and in patients. The mechanisms of action and the effect on portal hypertension of a series of drugs has further to be investigated. Experience gained till now in the cardiovascular domain will greatly speed up this process but fundamental research on neurohumeral processes involved will be further essential.

Adult↗

Genotype, serum level of HCV-RNA and response to interferon-alpha treatment in patients with chronic hepatitis C.

OBJECTIVE: Since only a small proportion of patients with chronic hepatitis C benefit from interferon therapy, we assessed the viral factors such as HCV genotype and the level of viraemia for prediction of interferon response. METHODS: HCV genotype and serum levels of HCV-RNA were determined in 24 patients before, during and after interferon treatment. RESULTS: Pre-treatment serum levels of HCV-RNA were significantly lower in patients with normalization of serum ALT and disappearance of serum HCV-RNA upon therapy than in patients with persistent abnormal ALT and/or serum HCV-RNA positivity. Sole infection with HCV genotype 1b was associated with a significantly higher pre-treatment serum HCV-RNA level than infection with genotype other than 1b or mixed types. CONCLUSIONS: HCV genotype and pre-treatment serum HCV-RNA levels are indeed important predictors for response to interferon treatment in patients with chronic hepatitis C.

Adolescent↗

Hepatitis C virus and its genotypes in patients suffering from chronic hepatitis C with or without a cryoglobulinemia-related syndrome.

Recently, evidence has been presented for a possible association between hepatitis C virus (HCV) infection and essential mixed cryoglobulinemia (EMC). Eleven consecutive patients with EMC and two with cryoglobulinemia type I were examined for the presence of markers of HCV infection. Eleven of 13 patients (10 with EMC and 1 with type I cryoglobulinemia) had anti-HCV antibodies (as determined by a second generation anti-HCV assay) and HCV-RNA in plasma or serum. HCV-RNA was also detected in liver biopsies of five patients. Genotyping showed that HCV genotype 1 was found in 10 of 11 patients with HCV-RNA (9 genotype 1b and 1 genotype 1a) and only one patient had HCV genotype 2. However, a similar high prevalence of genotype 1b (100%) was found in a group of 14 consecutive patients with chronic hepatitis C, who had no clinical evidence of cryoglobulinemia. Concomitant infection was present in three patients with genotypes 2, 3 and 4, respectively. These findings stress the high prevalence of HCV infection in patients with EMC and further study shows that a difference in genotype prevalence was not found between HCV-related EMC and chronic hepatitis C without clinical manifestations of EMC.

Adult↗

Clinical aspects of incomplete septal cirrhosis in comparison with macronodular cirrhosis.

BACKGROUND/AIMS: Incomplete septal cirrhosis (ISC) is a form of macronodular cirrhosis characterized by slender, incomplete septa that demarcate inconspicuous nodules. Its clinical features have not been investigated in a large series. The aims of this study were to review the clinical symptoms and evolution of ISC in 42 patients. METHODS: Forty-two patients with at least one liver biopsy strongly suggestive of ISC were selected for the study covering a period between 1968 and 1987. Data for these patients were compared with the evolution of 49 patients with classical macronodular cirrhosis after chronic active hepatitis type B or C. RESULTS: Possible etiological factors for ISC were alcohol abuse, arsenic treatment, and hepatitis B infection. In three cases, a genetic factor could not be excluded. Patients with ISC had significantly lower serum concentrations of transaminases and bilirubin at diagnosis. Compared with macronodular cirrhosis, bleeding varices were more frequent (57% vs. 22%) in ISC. Ten-year survivals in the ISC and the macronodular cirrhosis groups were 54% and 57%, respectively. CONCLUSIONS: ISC represents a relatively stable burnt-out form of macronodular cirrhosis with an unusually high incidence of variceal bleeding. This could be explained by a superimposed insufficiency of the portal vascular supply.

Adolescent↗

Detection of hepatitis C virus antigen by immuno-histochemical staining: a histological marker of hepatitis C virus infection.

Hepatitis C virus has been recognized as a major cause of non-A, non-B viral hepatitis. Although serologic tests have been commercialized, no specific histological or immuno-histochemical markers for hepatitis C virus infection are available for routine use. In an effort to detect hepatitis C virus antigen in liver tissue we investigated the immuno-reactivity to monoclonal antibodies on frozen liver tissue from a chimpanzee and patients with chronic non A, non B hepatitis. Monoclonal antibodies were developed in mice immunized with a synthetic peptide derived from hepatitis C virus core antigen. One monoclonal antibody was reactive and showed typical cytoplasmic granules in chimpanzee hepatocytes. Using this monoclonal antibody a similar staining pattern was found in the liver biopsies of 21 out of 28 chronic non-A, non-B hepatitis patients, positive for hepatitis C virus-RNA and anti-HCV. The granular immuno-reactivity was abolished after pre-incubation of this monoclonal antibody with infected chimpanzee liver or with hepatitis C virus synthetic peptide but not with normal chimpanzee or human liver tissue. There was no reactivity in four patients with hepatitis C virus-RNA-negative, anti-HCV-positive chronic non-A, non-B hepatitis, in 11 patients with chronic type B hepatitis or in 12 hepatitis C virus-RNA-negative, anti-HCV-negative patients with various liver diseases. However, staining was found in three out of four additional chronic type B hepatitis patients suspected of co-infection with non-A, non-B agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

The effect of different doses of a bolus injection of somatostatin combined with a slow infusion on transmural oesophageal variceal pressure in patients with cirrhosis.

Transmural variceal pressure was measured by fine-needle puncture following a 250-micrograms bolus injection of somatostatin given intravenously, together with a slow infusion of 250 micrograms/h, and compared with results following a 500-micrograms bolus and with placebo in 19 patients with cirrhosis who had recently bled. Pressure was recorded continuously for a 4-min period. Placebo did not alter variceal pressure (n = 6), whereas a 250- or 500-micrograms bolus produced a rapid decrease in pressure from 33 +/- 7 cmH2O to 20 +/- 6 (n = 7) and from 35 +/- 5 cmH2O to 24 +/- 6 (n = 6), respectively. The difference between the two groups was not significant. This decrease occurred within 30 to 90 s, but was followed by a progressive increase in variceal pressure over the next 2 min in all except two patients. After 3-4 min, variceal pressure still remained below pretreatment levels. Further studies are needed to evaluate the optimal infusion rate. These results seem to indicate that future clinical studies using somatostatin in the treatment of variceal haemorrhage should include repeated bolus injections to arrest variceal bleeding.

Blood Pressure Determination↗

Rapid clearance of hepatitis C virus RNA in peripheral blood mononuclear cells of patients with clotting disorders and chronic hepatitis C treated with alpha-2b interferon is not a predictor for sustained response to treatment.

Thirteen patients with congenital coagulation disorders and chronic hepatitis C were treated with alpha-interferon (IFN). Serum transaminases (ALT) and hepatitis C virus (HCV)-RNA in plasma and peripheral blood mononuclear cells (PBMC) were followed during and after treatment. During IFN treatment ALT levels normalized in 8/13 patients. In all patients HCV-RNA disappeared from PBMC. In 9/13 HCV-RNA also became undetectable from plasma; in six of these nine this occurred earlier in PBMC than in plasma; in the remaining three the disappearance of HCV-RNA occurred simultaneously in plasma and PBMC. All but two patients relapsed within 3 weeks after cessation of IFN, one relapsed after 6 weeks and one patient remains in remission after 6 months. HCV-RNA reappeared either earlier in plasma (3/12) or simultaneously in plasma and PBMC (9/12). Viral replication in PBMC thus can easily be suppressed by IFN, whereas longer treatment is needed for the eradication of HCV-RNA in plasma. The detection of HCV-RNA in PBMC cannot be used as a prognostic marker for the identification of patients with chronic hepatitis C who will have a sustained response to IFN treatment.

Adult↗

Measurement of variceal pressure and its clinical implications.

BACKGROUND: Recent investigations show that variceal pressure (VP) is more closely related to the risk of variceal bleeding than is the hepatic venous pressure gradient. As a consequence, the measurement and follow-up of VP is receiving more attention. METHODS AND RESULTS: Variceal pressure can be measured by the fine needle puncture technique. A close correlation with intrasplenic pressure recording and a high reproducibility in chronic conditions with this technique were confirmed in our laboratory. Using this technique, we recently demonstrated that an intravenous bolus injection of somatostatin 250 micrograms or 500 micrograms given together with a slow infusion of 250 micrograms/h yielded a rapid and transient decrease in VP. Our experience with the non-invasive pressure sensitive gauge shows that the procedure is easy to perform, well standardized and that it has a high reproducibility in acute conditions. CONCLUSION: We inferred from our study of the acute effect of somatostatin that, in the event somatostatin is used in the treatment of variceal haemorrhage, repeated bolus injection should be included to arrest the bleeding. The high accuracy of non-invasive VP measurements suggests that this technique may have an application in the follow-up of patients with oesophageal varices.

Esophageal and Gastric Varices↗

Plasma collected from heparinized blood is not suitable for HCV-RNA detection by conventional RT-PCR assay.

Detection of hepatitis C virus-RNA (HCV-RNA) in serum or in plasma is considered a reliable marker for ongoing HCV infection. HCV-RNA was measured routinely in plasma collected from heparinized blood of patients with chronic hepatitis C and varying results were found. In this study, HCV-RNA was detected in peripheral blood mononuclear cells (PBMCs) and in serum of 16 out of 17 anti-HCV positive patients with chronic hepatitis C. In contrast, HCV-RNA was found in plasma collected from heparinized blood of only one of these seventeen patients. The addition of heparin to known HCV-RNA containing solutions before reverse-transcription and separately before PCR, demonstrated the inhibitory effect of heparin on the reverse transcription and amplification reaction. Furthermore, evidence is provided that plasma for PCR should be collected preferably into EDTA vacutainers. It is concluded, therefore, that plasma collected from heparinized blood is not suitable for HCV-RNA determination by RT-PCR. In addition, PBMCs might play an important role in the pathobiology of hepatitis C virus, since HCV-RNA was easily detected in PBMC of patients with chronic hepatitis C.

False Negative Reactions↗

Treatment of decompensated viral hepatitis B-induced cirrhosis with low doses of interferon alpha.

Seven patients with decompensated posthepatitis B cirrhosis were treated with low doses of interferon alpha. The initial plasma level of HBV-DNA ranged from 3.0 to 189.3 pg/ml, and that of ALT from 37 to 156 IU/l. Liver biopsies demonstrated ongoing piecemeal necrosis. In sera of all but one patient, HBV-DNA became undetectable by hybridisation techniques within 10 to 28 weeks. Plasma HBeAg became negative in four and HBe-antibodies positive in three patients. Serum transaminase levels showed a marked initial rise 3 to 13 weeks after onset of therapy; they dropped to normal values later in all except one patient. Therapy was initiated at 1 MU (million units) three times a week for 2 weeks and was increased to 2.5 MU for 16 weeks. Later, this dosage was raised to 5 MU three times a week in some patients. Complications included variceal haemorrhage, aggravation of ascites or of encephalopathy, development of pneumonia, recurrence of spontaneous bacterial peritonitis or of gastric ulcer bleeding. One year after stopping the therapy, three patients are well and without any feature of liver decompensation. Three patients died before they could undergo a liver transplantation. In one patient treatment was interrupted because of marked exacerbation of liver cell necrosis. It thus seems possible to suppress HBeAg and HBV-DNA in patients with decompensated cirrhosis. This is important to prepare them for possible liver transplantation. Interferon should be initiated at low doses and the patients be very carefully monitored. Prophylactic therapy for bacterial peritonitis and for variceal haemorrhage is warranted.

Alanine Transaminase↗

Prospective study on prevalence of esophageal chest pain in patients referred on an elective basis to a cardiac unit for suspected myocardial ischemia.

The prevalence of esophageal chest pain was studied prospectively in patients referred on an elective basis to a cardiac unit for suspected myocardial ischemia. A group of 248 consecutive patients without previously documented heart disease was admitted for elective diagnostic coronary angiography. The clinical history classified 185 patients as having anginal pain and the coronary angiogram was normal in 48 of them. In 37 of these 48 patients full esophageal testing was performed including 24-hr intraesophageal pH and pressure recordings with indication of chest pain episodes as well as a number of esophageal provocation tests, ie, acid perfusion, edrophonium stimulation, balloon distension, and ergonovine stimulation, all performed under continuous esophageal manometric and electrocardiographic monitoring. In 19 of these 37 patients, the familiar chest pain could be reproduced by esophageal provocative testing without ischemic ST-T segment alterations; six of these 19 patients had also a positive 24-hr pH and pressure recording. These data strongly suggest an esophageal origin of chest pain in half the patients with typical angina and a normal coronary angiogram.

Angina Pectoris↗

Effects of ritanserin, a selective and specific S2-serotonergic antagonist, on portal pressure and splanchnic hemodynamics in portal hypertensive rats.

Serotonergic mechanisms have recently been implicated in the pathogenesis of portal hypertension; this suggests that blockade of serotonin S2 receptors may be a new approach for the pharmacological therapy of portal hypertension. This study was aimed at investigating the effects of ritanserin, a selective S2-serotonergic antagonist, in portal-hypertensive rats whose condition was due to partial portal vein ligation. The animals were randomized under double-blind conditions into two groups: the first received ritanserin (0.7 mg/kg body wt, intravenously), and the second received the same volume of placebo (isotonic saline solution). The hemodynamic studies were performed using radiolabeled microspheres 60 min after drug administration. Ritanserin administration significantly reduced portal pressure (from 11.8 +/- 0.8 mm Hg to 9.4 +/- 0.6 mm Hg; p less than 0.05). This was associated with lower portocollateral resistance (1.8 +/- 0.2 mm Hg/ml/min 100 gm in the ritanserin group vs. 2.3 +/- 0.2 mm Hg/ml/min 100 gm in rats receiving placebo; not significant), but we saw no changes in portal-vein inflow (5.5 +/- 0.7 ml/min 100 gm vs. 5.4 +/- 0.5 ml/min 100 gm), mean arterial pressure (95.9 +/- 3.5 mm Hg vs. 94.0 +/- 4.0 mm Hg) and cardiac index (31.9 +/- 3.5 ml/min 100 gm vs. 28.5 +/- 2.6 ml/min 100 gm). Hepatic arterial and kidney blood flows were not modified by ritanserin. In summary, our results demonstrate that ritanserin infusion decreases portal pressure without causing systemic hemodynamic changes. This effect is probably due to a decrease in portocollateral resistance in portal-hypertensive rats. These results provide further for a role of serotonin in the pathogenesis of portal hypertension.

Animals↗

Reversal of hepatorenal syndrome in four patients by peroral misoprostol (prostaglandin E1 analogue) and albumin administration.

Four consecutive patients with alcoholic cirrhosis and hepatorenal syndrome were treated with misoprostol, a synthetic methylester prostaglandin E1 analogue at twice the dosage advocated for anti-ulcer therapy (i.e., 0.4 mg four times per day orally) and albumin infusions. The mean urinary output obtained over the 3 days preceding misoprostol administration was 250, 315, 550 and 195 ml per 24 h, respectively, in the four patients, despite adequate volume expansion by plasma albumin to reach normal or high central venous pressure. Diuresis increased to 1450, 2440, 925 and 1300 ml, respectively, on days 2-4 after onset of therapy. Serum creatinine levels were 71, 51, 33 and 35 mg/l before and dropped to 26, 21, 13 and 17 mg/l during treatment. All patients had hyponatraemia (117-128 mequiv/l) which normalized, although they were continued on a low sodium intake of less than 10 mequiv per 24 h. Urinary sodium excretion increased from 0.4-3 mmol per 24 h, to 15-40 in the first two cases and only slightly to 3-5 in the last two patients. Three patients died after 10, 30 and 40 days due to oesophageal bleeding, encephalopathy or pulmonary infection, whereas one patient underwent an orthotopic liver transplantation when her serum creatinine attained a level of 13 mg/l. In the first patient, hepatorenal syndrome recurred 10 days after stopping the misoprostol treatment. High doses of misoprostol in the presence of adequate volume expansion thus seem to produce marked diuresis and creatininuria as well as mild natriuresis.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Efficacy of interferon alfa-2b with or without prednisone withdrawal in the treatment of chronic viral hepatitis B. A prospective double-blind Belgian-Dutch study.

A prospective, double-blind study was carried out to assess the efficacy of interferon alfa-2b, with or without pre-treatment prednisone withdrawal, in patients with chronic hepatitis B. A total of 57 Belgian and Dutch patients were included in the study. Patients were divided into four treatment groups: Group A, prednisone withdrawal followed by interferon 5 million units per day; Groups B and C, placebo followed by interferon 5 or 1 million units, respectively; and Group D, untreated controls followed for 1 year. All treated patients received interferon for 16 weeks. Two of the 14 control patients lost hepatitis B e antigen during the year of study, and only one of 15 patients in the interferon 1 million units group. Among the 28 patients receiving 5 million units of interferon (with or without prednisone withdrawal), ten (36%) cleared hepatitis B e antigen during the study or within 6 months of the end of therapy. This was associated with a marked improvement in serum transaminase levels. When comparing Groups A and B, it was found that prednisone withdrawal therapy enhanced the response to interferon in patients with pre-treatment serum alanine aminotransferase levels below 100 IU/l, bringing the seroconversion rate up to 50%, compared to 17% on interferon alone. This effect was not seen in patients with high pre-treatment transaminase levels. All treatment responders showed a marked improvement in Knodell index score, whereas in the 15 non-responders from groups A and B, overall inflammatory activity remained the same in six, improved in five and worsened in four.(ABSTRACT TRUNCATED AT 250 WORDS)

Belgium↗