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Biomedical subjects

D Vetter

Publications and source records attributed to D Vetter.

At least 19 recordsLinked to original sources
PubMed2003

Retreatment with interferon and ribavirin vs interferon alone according to viraemia in interferon responder-relapser hepatitis C patients: a prospective multicentre randomized controlled study.

Low pretreatment viral load has consistently been shown to be an independent predictor of sustained response (SR) in patients with chronic hepatitis C infection. We assessed the efficacy of interferon (IFN) plus ribavirin vs IFN alone in low viraemic patients (<2 millions copies/mL) who had relapsed to a previous course of IFN and the efficacy of 24 vs 48 week combination therapy in high viraemic patients. Two hundred and ninety-seven patients were randomly assigned to one of the four regimens after stratification on pretreatment viral load. All patients received IFN-alpha2b (6 million units thrice weekly for 24 weeks and 3 million units thrice weekly for 24 weeks). Patients with low viraemia received either IFN-alpha2b alone for 48 weeks (R1: 42 patients) or IFN-alpha2b plus ribavirin (600 mg/day) for 24 weeks and IFN-alpha2b alone for the next 24 weeks (R2: 48 patients). Patients with high viral load received either IFN-alpha2b plus ribavirin for 24 weeks and then IFN-alpha2b alone for the next 24 weeks (R3: 104 patients) or IFN-alpha2b plus ribavirin for 48 weeks (R4: 103 patients). In low viraemic patients the rate of SR was 37.7% in group R1 and 59.6% in group R2 (P < 0.05). In high viraemic patients, the rate of SR was 44.7% in group R3 and 51.4% in group R4 (P: NS). Thirty-one patients discontinued treatment (10.4%) without difference regarding treatment regimen. In the regimen using ribavirin we found no difference in terms of SR between patients receiving a dose of ribavirin below 10.6 mg/kg/day (55%) or over 10.6 mg/kg/day (58%). Histological improvement occurred in 70.2% of patients regardless of the regimen. Logistic regression showed that genotype 2 and 3, Knodell score <6 and alanine aminotransferase pretreatment level >3 x upper limit of normal were significantly and independently correlated with SR. In low viraemic patients who relapsed to a previous IFN treatment, combination therapy using high-dose IFN and low-dose ribavirin is better than high-dose IFN alone. In high viraemic patients there was no benefit in increasing the duration of combination therapy from 24 to 48 weeks. In this study, it was found that low dose of ribavirin can be used safely and there is no effect of ribavirin dose on SR.

Adult↗
PubMed2002

Whiplash injury: cases with a long period of sick leave need biomechanical assessment.

A total of 668 cases of cervical spine disorders (CSD) sustained in automotive collisions were analysed. All cases had a minimum sick leave duration of 4 weeks. To evaluate these cases a scheme was developed that takes into account technical, medical, and biomechanical aspects. For each case, the delta-v value of the underlying collision was estimated, the medical files were analysed, and a QTF (Québec Task Force) grade was assigned. In addition, the medical history of the patient was reviewed. It was found that the QTF grade for patients with pre-existing damage of the neck or pre-existing signs differed significantly from those patients without such a history. The overall assessment, which stated the extent to which the symptoms claimed could be explained by the impact, was also found to be significantly influenced by a history of neck injury. The results of the study showed that in about 50% of the cases where the technical analysis alone would not suggest that the symptoms shown could be explained by the impact, those symptoms could be explained when patient history and the collision circumstances were taken into consideration. It also found that medical evaluation based on a QTF grade alone cannot assess the explicability of claimed CSD without taking into account the collision circumstances. Therefore, the assessment of critical individual relevant biomechanical factors is necessary.

Accidents, Traffic↗
PubMed2000

Both beta(2)- and beta(1)-adrenergic receptors mediate hastened relaxation and phosphorylation of phospholamban and troponin I in ventricular myocardium of Fallot infants, consistent with selective coupling of beta(2)-adrenergic receptors to G(s)-protein.

BACKGROUND: In adult human heart, both beta(1)- and beta(2)-adrenergic receptors mediate hastening of relaxation; however, it is unknown whether this also occurs in infant heart. We compared the effects of stimulation of beta(1)- and beta(2)-adrenergic receptors on relaxation and phosphorylation of phospholamban and troponin I in ventricle obtained from infants with tetralogy of Fallot. METHODS AND RESULTS: Myocardium dissected from the right ventricular outflow tract of 27 infants (age range 21/2 to 35 months) with tetralogy of Fallot was set up to contract 60 times per minute. Selective stimulation of beta(1)-adrenergic receptors with (-)-norepinephrine (NE) and beta(2)-adrenergic receptors with (-)-epinephrine (EPI) evoked phosphorylation of phospholamban (at serine-16 and threonine-17) and troponin I and caused concentration-dependent increases in contractile force (-log EC(50) [mol/L] NE 5.5+/-0.1, n=12; EPI 5.6+/-0.1, n=13 patients), hastening of the time to reach peak force (-log EC(50) [mol/L] NE 5.8+/-0.2; EPI 5.8+/-0.2) and 50% relaxation (-log EC(50) [mol/L] NE 5.7+/-0.2; EPI 5.8+/-0.1). Ventricular membranes from Fallot infants, labeled with (-)-[(125)I]-cyanopindolol, revealed a greater percentage of beta(1)- (71%) than beta(2)-adrenergic receptors (29%). Binding of (-)-epinephrine to beta(2)-receptors underwent greater GTP shifts than binding of (-)-norepinephrine to beta(1)-receptors. CONCLUSIONS: Despite their low density, beta(2)-adrenergic receptors are nearly as effective as beta(1)-adrenergic receptors of infant Fallot ventricle in enhancing contraction, relaxation, and phosphorylation of phospholamban and troponin I, consistent with selective coupling to G(s)-protein.

Calcium-Binding Proteins↗
PubMed2000

Increasing the number of hepatitis B vaccine injections augments anti-HBs response rate in HIV-infected patients. Effects on HIV-1 viral load.

Preventing hepatitis B by vaccination is essential in HIV-infected patients (higher progression rate of HBV infection to chronicity, lower rate of serum HBe Ag loss). However, it has been shown a decreased anti-HBs response in these individuals after a standard vaccination (3 doses of 20 micrograms). Thus, we tested the hypothesis that doubling the number of hepatitis B vaccine injections might increase anti-HBs response rate. HIV-infected patients with CD4 > 200/microliter, who were on stable antiretroviral treatment, as well as seronegative for HBV markers, and who have never been vaccinated against HBV, were given 3 intramuscular injections of Genhevac B 20 micrograms at 1 month intervals. Initial non responders were given 3 additional monthly injections. Anti-HBs titer was followed. We also evaluated the effects on HIV-1 viral load. Twenty patients with a median CD4 cell count of 470/microliter were enrolled. The response rate after three 20 micrograms injections was 55% (11/20), lower in individuals with CD4 between 200 and 500/microliter (4/12 = 33.3%), compared to patients with CD4 above 500/microliter (7/8 = 87.5%, P = 0.02). Among 9 initial non-responders, only 2 did not respond to 3 additional doses; thus, the overall response rate was 90% (18/20). Geometric mean titers of anti-HBs were 133 IU/l and 77.5 IU/l, after 3 and 6 Genhevac doses, respectively (P = 0.38). One year later, only 10/17 (58.8%) patients had protective anti-HBs. Five patients experienced a significant viral load increase, transient in 3 cases. These preliminary results suggest that doubling the number of hepatitis B vaccinations in HIV-infected patients might significantly improve anti-HBs response rate; however, close monitoring of anti-HBs is necessary because of its short-lived persistence. The effects on HIV-1 viral load are limited.

Adult↗
PubMed2000

Phosphorylation of phospholamban at threonine-17 in the absence and presence of beta-adrenergic stimulation in neonatal rat cardiomyocytes.

The site-specific phospholamban phosphorylation was studied with respect to the interplay of cAMP- and Ca(2+)signaling in neonatal rat cardiomyocytes. To elucidate the signal pathway(s) for the activation of Ca(2+)/calmodulin-dependent protein kinase (CaMKII) we studied Thr17 phosphorylation of phospholamban in dependence of Ca(2+)channel activation by S(-)-Bay K8644 and in dependence of the depletion of the sarcoplasmic reticulum Ca(2+)stores by ryanodine or thapsigargin in the absence or presence of beta -adrenergic stimulation. The isoproterenol (0.1 microM)-induced Thr17 phosphorylation was potentiated 2.5-fold in presence of 1 microM S(-)-Bay K8644. Interestingly, S(-)-Bay K8644 alone was also able to induce Thr17 phosphorylation in a dose- and time-dependent fashion. Ryanodine (1.0 microM) reduced both the isoproterenol (0.1 microM) and S(-)-Bay K8644-(1 microM) mediated Thr17 phosphorylation by about 90%. Thapsigargin (1 microM) diminished the S(-)-Bay K8644 and isoproterenol-associated Thr17 phosphorylation by 53.5+/-6.3% and 92. 5+/-11.1%, respectively. Ser16 phosphorylation was not affected under these conditions. KN-93 reduced the Thr17 phosphorylation by S(-)-Bay K8644 and isoproterenol to levels of 1.1+/-0.3% and 8.6+/-2. 1%, respectively. However, the effect of KN-93 was attenuated (47. 8+/-3.6%) in isoproterenol prestimulated cells. Protein phosphatase inhibition by okadaic acid increased exclusively the Ser16 phosphorylation. In summary, our results reflect a cross-talk between beta -adrenoceptor stimulation and intracellular Ca(2+)at the level of CaMKII-mediated phospholamban phosphorylation in neonatal rat cardiomyocytes. We report conditions which exclusively produce Thr17 or Ser16 phosphorylation. We postulate that Ca(2+)transport systems of the sarcoplasmic reticulum are critical determinants for the activation of CaMKII that catalyzes phosphorylation of phospholamban.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2000

Single bead parallel synthesis and screening.

Microstructured silicon wafers were employed as miniaturized solid-phase reaction vessels as well as miniaturized micro titer plates. Employing piezoelectric drop-on-demand liquid jets, a combinatorial library of 256 Peptides was synthesized on single beads. The synthesis protocol was associated to the location in the silicon nano-well arrangement. Products were photolytically cleaved in the same well that was used for synthesis and subsequently interrogated for thrombin inhibition in a homogeneous competition assay. The assay procedure was based on drop-on-demand liquid delivery and laser induced fluorescence imaging. The novel format proved useful for the integration of both synthesis and screening into one platform, a prerequisite for an iterative, evolutionary approach towards drug discovery.

Chromatography, High Pressure Liquid↗
PubMed2000

Randomized trial of interferon-alpha plus ursodeoxycholic acid versus interferon plus placebo in patients with chronic hepatitis C resistant to interferon.

BACKGROUND: Ursodeoxycholic acid (UDCA) could potentiate the effect of interferon (IFN) in patients with chronic hepatitis C resistant to IFN. We compared the efficacy of IFN with that of a combination of IFN and UDCA. METHODS: Patients were randomized to receive UDCA (13-15 mg/kg/day) (n = 47) or placebo (n = 44) plus interferon (3 MU three times weekly) for 6 months and were then followed up for 6 additional months. RESULTS: At entry 30% of patients had cirrhosis, and 70% had HCV genotype 1. Five and four patients withdrew from the combination and the monotherapy groups, respectively. At 6 months alanine aminotransferase (ALAT) and gamma-glutamyl transferase (GGT) activities were significantly lower (P < 0.001) in the combination group than in the monotherapy group; the differences were no longer significant at 1 year. At 6 months ALAT activities normalized in 10 and 8 patients in the combination and the monotherapy groups, respectively (P = 0.67). In 10 of them (5 in each group) HCV RNA levels became undetectable. At 1 year four versus one patient had a sustained normalization of ALAT, and in one patient the HCV RNA became negative. There was no difference in the histologic progression. In this setting, in contrast to chronic cholestasis, UDCA administration induced an increase in total serum bile acids and did not change primary bile acids. CONCLUSIONS: An IFN plus UDCA combination is more effective than IFN alone in terms of ALAT but not in terms of the virologic response. These results favor the hypothesis that UDCA has an effect on the biochemical indices of cellular injury independent of a change in primary bile acids.

Adult↗
PubMed1999

Follow-up of hepatitis C virus RNA in peripheral blood mononuclear cells during interferon therapy.

Mononuclear cells can be infected in vitro by hepatitis C virus and the viral RNA can be detected in mononuclear cells of chronically infected patients. It was suggested that the virus could persist in the mononuclear cells of some patients treated by interferon. The aim of this study was to follow the presence of viral RNA in the plasma and peripheral blood mononuclear cells of 16 chronically infected patients treated by alpha 2b interferon for 1 year. The RNA was detected by reverse transcription followed by nested PCR and quantified using the branched DNA method at regular intervals for at least one year. Before PCR, the mononuclear cells were treated by RNase and trypsin in order to eliminate the viral particles that could be stuck at the cell surface. Six patients were non responders and had persistent plasmatic viral RNA during the treatment. Two patients were good responders and had persistently negative PCR in both plasma and mononuclear cells. Eight patients had initial negativation of plasmatic hepatitis C virus RNA but showed a relapse characterized by positive plasmatic PCR. Positive PCR in mononuclear cells despite negativity of plasmatic PCR was noted 18 times in 8 patients. Persistently positive PCR in mononuclear cells in absence of detectable viraemia was followed by a virological relapse in 5 of these patients. This study confirms that hepatitis C virus RNA can be detected in mononuclear cells despite negative plasmatic PCR in patients treated by interferon. Moreover, the persistence of viral RNA in peripheral mononuclear cells could be a predictive factor of treatment failure. Our data also suggest that detection of viral RNA in mononuclear cells is probably not only due to passive virus adsorption from plasma.

Adult↗
PubMed1999

Lack of effect of propranolol in the prevention of large oesophageal varices in patients with cirrhosis: a randomized trial. French-Speaking Club for the Study of Portal Hypertension.

OBJECTIVE: Beta-blockers have been shown to reduce portal pressure in patients with cirrhosis and limit the development of portosystemic shunts in portal hypertensive animals. Thus, a randomized double-blind trial was conducted to evaluate propranolol in the prevention of the development of large oesophageal varices in patients with cirrhosis without varices or with small varices. METHODS: One hundred and two patients received long-acting propranolol (160 mg/day) and 104 patients received a placebo. At inclusion, there was no significant difference between the two groups in terms of clinical characteristics or biochemical tests. At 2 years, the size of varices was estimated on video recordings. RESULTS: One-third of the patients were lost to follow-up, and 95%/97% of the remaining patients were compliant in the propranolol and placebo groups, respectively. At 2 years, the proportion of patients with large varices was 31% in the propranolol group and 14% in the placebo group (P< 0.05). Three and four patients bled in the propranolol and placebo groups, respectively, and nine and ten died, respectively. CONCLUSION: This trial suggests that propranolol administration cannot be recommended for the prevention of the development of large oesophageal varices in patients with cirrhosis; thus other studies are needed in selected subgroups of patients.

Adrenergic beta-Antagonists↗
PubMed1998

Systematic cutaneous examination in hepatitis C virus infected patients.

The purpose of this study was to evaluate the frequency of skin changes among 100 patients from the Hepatogastroenterology Department of the University Hospital, Strasbourg, France who were hepatitis C virus-positive (HCV) and HIV-negative. Their clinical data were compared to those of 50 HCV-, and HIV-negative patients from the same Department, who suffered from various liver diseases. Psoriasis, rosacea, seborrheic dermatitis, cherry angiomas, spider nevus and skin cancers were noted in similar proportions in the two groups. In 15% of HCV-positive patients vs. 4% of controls, chronic pruritus was noted (p < 0.05). In 9 HCV-positive patients, pruritus was not related to itching dermatosis, and only 2 of these patients had mild cholestasis. Four cases of lichen planus vs. 0 in the control group were recorded. The virological data of patients with pruritus or lichen planus were not different than those of the rest of the group. Our findings indicate that systematic skin check-up in HCV-positive patients is valuable.

Adult↗
PubMed1998

[Chemoembolization techniques for hepatocellular carcinoma in cirrhosis].

Transcatherter oily chemoembolisation, that should not be confused with other different and less effective techniques also called "chemoembolisation" is the most widely used therapy for loco-regional palliative treatment of hepatocellular carcinoma, which will become increasingly frequent, due to HCV infection; the cancer itself is often discovered at an advanced stage, when neoplastic extension precludes radical treatment that is liver transplantation. Performed with the best techniques, it offers a 1- and 5-yr survival of 60 and 30%, that is under confirmation by a randomized trial.

Carcinoma, Hepatocellular↗
PubMed1997

[Etiological treatment of cirrhosis in adults].

Etiological treatment is based upon: abstinence in case of alcoholic cirrhosis; alpha-interferon in case of B or C viral cirrhosis; corticosteroids in case of autoimmune cirrhosis; ursodeoxycholic acid in case of primary biliary cirrhosis; stopping the drug in case of drug-induced cirrhosis; surgery in case of secondary biliary cirrhosis; venesections in case of genetic haemochromatosis; liver transplantation in cases of Wilson's disease and alpha 1-anti-trypsin deficiency. Overall, these treatment are more effective when undertaken early in the course of the liver disease.

Adult↗
PubMed1997

Lymphocyte reactivity to hepatitis C virus (HCV) antigens shows evidence for exposure to HCV in HCV-seronegative spouses of HCV-infected patients.

Lymphocyte reactivity against hepatitis C virus (HCV) antigens was studied in 20 couples in which 1 member had chronic hepatitis C. This was done to investigate the possibility of HCV transmission between spouses that was not followed by seroconversion. Twenty healthy subjects without any risk factors for HCV transmission served as negative controls. All the patients' spouses and the healthy controls were negative for HCV RNA and for anti-HCV antibody. Lymphocytes were cultured with recombinant HCV core and nonstructural antigens (c22, c33, c100, c200, and NS5) and with control antigens (sperm whale myoglobin, chicken lysozyme, and superoxide dismutase). Lymphocytes from 10 patients and 4 seronegative spouses proliferated in the presence of at least one HCV antigen. No proliferation was shown with nonspecific antigens or in the control group. This study gives evidence for possible in vivo priming with HCV antigens that did not lead to seroconversion in spouses of HCV-positive patients.

Adult↗
PubMed1997

[Comparison of immunogenicity of vaccination and serovaccination against hepatitis B virus in patients with alcoholic cirrhosis].

OBJECTIVES: The association of anti-HBs immunoglobulins and anti-HBV vaccine could increase the immunogenicity of the latter. The aim of this prospective randomized trial was to compare the immunogenicity of anti-HBs vaccination and serovaccination in alcoholic patients with cirrhosis. METHODS: Alcoholic patients with cirrhosis were randomized in 2 groups: a) Vaccination group: 3 i.m. injections of GenHevac B followed by one booster at month 9; b) Serovaccination group: same vaccination schedule followed by one i.m. injection of anti-HBs immunoglobulins (500 IU). RESULTS: Twenty-five patients (17 males and 8 females, mean age 56 years) were included in the study: 13 received a vaccination and 12 received a serovaccination. After 12 months, the seroconversion rates were 69% and 67% in vaccination and in serovaccination groups, respectively. The predictive factors of non responsiveness were as following: Child B cirrhosis, low number of CD8, a high CD4/CD8 rate, the existence of HLA DR7 antigen, and the absence of HLA DR1 antigen. CONCLUSION: In alcoholic patients with cirrhosis, serovaccination does not increase the immunogenicity of anti-HBs vaccination and should not be recommended.

Female↗
PubMed1996

Comparison of resection, liver transplantation and transcatheter oily chemoembolization in the treatment of hepatocellular carcinoma.

BACKGROUND/AIMS: Resection and liver transplantation are currently considered as the most useful treatments for hepatocellular carcinoma. However, transcatheter oily chemoembolization may be favourably compared with these two surgical treatments in patients with anatomically operable tumors. METHODS: Between 1985 and 1991, 122 patients with an Okuda stage I tumor were hospitalized in two French hospitals. Among these patients, 33 remained untreated, 42 were treated by transcatheter oily chemoembolization, 30 by resection and 17 by liver transplantation. The four groups were closely comparable except for age, the patients in the two surgical groups being significantly younger. Moreover, the frequency of pTNM II tumor was significantly higher in the resection group. RESULTS: The 5-year probability of survival was close to 45% in each of the three treated groups and was significantly higher than in the untreated group (0% at 4 years, p < 0.0001). The probability of cancer recurrence and/or metastatic dissemination was lower after transcatheter oily chemoembolization than after surgery. CONCLUSION: Thus, transcatheter oily chemoembolization seems comparable at 5 years with resection or transplantation for the treatment of resectable hepatocellular carcinoma.

Aged↗