PubMed Health⌕ Search

Biomedical subjects

R A de Man

Publications and source records attributed to R A de Man.

At least 73 records · Page 4Linked to original sources
PubMed2000

Budd-Chiari syndrome: combination of genetic defects and the use of oral contraceptives leading to hypercoagulability.

A young female, who had been in excellent health and had used third-generation oral contraceptives, was admitted to hospital because of abdominal pain and ascites. Budd-Chiari syndrome (BCS) was diagnosed by radiographic and histological examination. Tests for myeloproliferative disease, deficiency of coagulation inhibitors and paroxysmal nocturnal haemoglobinuria were negative. DNA investigation showed a double heterozygous defect: the Arg506Gln mutation in the factor V gene (factor V Leiden) and G20210A nucleotide substitution in the prothrombin gene. This double defect was also found in the patient's father, who had never experienced an episode of venous thromboembolism. Genetic and acquired thrombogenic risk factors are being detected increasingly in patients with BCS. With the discovery of new genetic defects leading to hypercoagulabiulity an increasing number of patients with serious thrombotic manifestations, such as BCS, will exhibit concurrence of hereditary and acquired risk factors for thrombosis.

Adolescent↗
PubMed2000

Lamivudine-high dose interferon combination therapy for chronic hepatitis B patients co-infected with the hepatitis D virus.

Currently, the best option for patients with hepatitis delta is interferon alpha therapy for at least one year. To evaluate the effect of the combination lamivudine-high-dose interferon alpha therapy, we first treated eight patients with chronic hepatitis delta infection with lamivudine for at least 24 weeks; then lamivudine was combined with a high dose of interferon alpha followed by a regular dose (9 MU tiw). Follow-up was 12 weeks. Virological, biochemical and histological features were evaluated for response to therapy. At baseline, all patients were HBsAg positive in serum and HDV RNA-(PCR)positive in plasma; HBV DNA was undetectable with the Digene Hybrid Capture assay (limit of detection 1.5 x 10(6) geq ml-(1)) in all cases. Transaminases were elevated in all patients; median ALT 68 (range 48-143) IU l(1). Seven of eight patients completed the course; one patient with a pre-existing sickle cell trait was withdrawn from the trial due to the development of a nephrotic syndrome. The HBsAg-concentration in serum decreased in two out of seven patients (29%). However, there was no significant decrease in the HBsAg-concentration in serum during treatment (median 3654 PEU l(-1) (range 548-7,684) to 5300 PEU l(-1) (range 168-19,639)). The drop of HDV RNA in plasma from baseline during treatment was not significant. Decrease of HDV RNA was observed in three out of seven patients (43%) (median 10(5) geq ml(-1); range 10(3)-10(6) to median 10(3) geq ml(-1); range 10(2)-10(7)). Serum ALT did not change as reflected by a median of 68 IU l(-1) (range 48-143) at start of therapy to 63 IU l(-1) (range 20-171) at the end of therapy. At the end of treatment transaminases had normalised in one patient and decreased in three other patients (improvement in 57%). However, three of these four patients showed a rebound after withdrawal of therapy. The Histology Activity Index (HAI) indicated a drop from a median score of 7 (range 5-9) at baseline to 5 (range 3-8) at the end of treatment, but an increase in fibrosis from a median grade of 2 (range 1-3) at baseline to 3 (range 1-4) at the end of treatment was observed. In conclusion, this study does not yield support for the combination of an HBV suppressor and 16 weeks of high-dose interferon for therapy aimed at eradicating the hepatitis delta virus.

Adult↗
PubMed2000

Acute exacerbation of chronic hepatitis B virus infection after withdrawal of lamivudine therapy.

Acute exacerbations of chronic hepatitis B virus (HBV) infection occur after withdrawal of lamivudine therapy in approximately 16% of patients and are considered of little clinical significance. We observed "lamivudine withdrawal hepatitis" accompanied by jaundice and incipient liver failure, but also followed by complete recovery and viral clearance. To investigate the incidence, severity, timing, and virologic characteristics of "lamivudine withdrawal hepatitis" we monitored 41 patients for at least 6 months after discontinuation of nucleoside analogue therapy. The incidence of hepatitis flares was estimated to be 7 of 41 (17%); in 2 of 41 cases (5%), hepatitis flares were associated with jaundice and incipient liver failure. A noticeable feature of the "lamivudine withdrawal hepatitis" flares were the high HBV-DNA levels at the time of the alanine transaminase (ALT) peak. All were wild-type HBV, even the one that emerged from a lamivudine-resistant strain during therapy. To minimize the risk of liver failure and to enhance the elimination of HBV following flares, lamivudine therapy was reinstituted in an icteric patient. Clinical and biochemical remission ensued, followed by loss of HBV DNA and hepatitis B e antigen (HBeAg) seroconversion. Such a virologic response did not occur in 5 other patients with a nonicteric "lamivudine withdrawal hepatitis," who were not retreated with lamivudine. Hepatitis after withdrawal of lamivudine resembles acute hepatitis B with a predominance of anicteric flares within a time frame of 6 months. Active management of hepatitis flares following withdrawal of nucleoside analogue therapy should be investigated further.

Adult↗
PubMed2000

A randomized, placebo-controlled study to evaluate the efficacy of 12-month famciclovir treatment in patients with chronic hepatitis B e antigen-positive hepatitis B.

We conducted a randomized, placebo-controlled clinical study evaluating famciclovir (500 mg 3 times daily and 1.5 g once daily) for 1 year (6 months post-treatment follow-up) in patients with chronic hepatitis B e antigen (HBeAg)-positive hepatitis B virus (HBV) infection. The study was conducted in 80 centers in North America, Europe, and Australia/New Zealand. A total of 417 patients with histologically documented chronic hepatitis B (histologic activity index [HAI] 9.5-11.0) received famciclovir (500 mg 3 times daily or 1.5 g once daily) or placebo. Famciclovir 500 mg 3 times daily significantly reduced HBV DNA and median HAI scores versus placebo. By week 8, median HBV DNA decreased from 1,645 to 283 MEq/mL (famciclovir 500 mg 3 times daily) and from 1,147 to 304 MEq/mL (famciclovir 1.5 g once daily), while increasing for placebo (1,617 to 1,685 MEq/mL). Median change in HBV DNA at the end of therapy was -76% (famciclovir 500 mg 3 times daily; P <.01) and -60% (famciclovir 1.5 g once daily; P =.25) versus -37% for placebo. Median change in HAI was -1.5 points (famciclovir 500 mg 3 times daily; P =.02) and -1.0 point (famciclovir 1.5 g once daily; P =.35) and zero for placebo. Fifty percent of patients receiving famciclovir 500 mg 3 times daily (P =.07) and 43% receiving 1.5 g once daily (P =.41) experienced >/=2 points improvement in HAI versus 37% for placebo. Nine percent of patients treated with famciclovir 500 mg 3 times daily underwent anti-HBeAg seroconversion with undetectable HBV DNA at end of follow-up versus 3% in the placebo group (P =.05). Famciclovir was well tolerated; the incidence of post-treatment alanine transaminase (ALT) elevations was comparable with placebo. In conclusion, famciclovir 500 mg 3 times daily gave modest suppression of viral replication, but translated into significant histologic improvement in median HAI score at 1 year.

2-Aminopurine↗
PubMed2000

Aspergillus osteomyelitis after liver transplantation: conservative or surgical treatment?

We report on a liver transplant recipient who developed coxarthritis and lumbar spondylodiscitis due to Aspergillus flavus. He was treated with high-dose liposomal amphotericin B for 2 months followed by itraconazole. Because of intractable pain and severe, irreversible damage of the left hip, a Girdlestone resection was performed. The spondylodiscitis was treated successfully with anti-fungal agents only, which indicates that, in the absence of neurological impairment, good clinical outcome can be achieved without surgery. This case demonstrates that surgical therapy, which is often proclaimed as unavoidable for the treatment of Aspergillus osteomyelitis, should be considered in particular in the case of intolerable pain due to irreversible joint damage or involvement of vital organs.

Adult↗
PubMed2000

The prognostic significance of subclinical hepatic encephalopathy.

OBJECTIVE: Subclinical hepatic encephalopathy may have prognostic significance with regard to the development of clinical hepatic encephalopathy and survival. METHODS: We studied 116 consecutive patients with histologically proven cirrhosis of the liver for subclinical hepatic encephalopathy, using Number Connection Test A, Digit Symbol Test, and spectral analysis of the electroencephalogram. RESULTS: Twenty-five patients (22%) were diagnosed as having subclinical hepatic encephalopathy. Patients with subclinical hepatic encephalopathy were older, had a higher Child-Pugh score, and more often had esophageal or gastric varices and episode(s) of clinical hepatic encephalopathy in their history. During a median follow-up of 29 months (range, 1-49 months), patients with subclinical hepatic encephalopathy significantly more often had episodes of clinical hepatic encephalopathy; survival, however, was similar to that of patients without subclinical hepatic encephalopathy, and was determined mainly by the Child-Pugh score. The Child-Pugh score was also superior to subclinical hepatic encephalopathy in predicting episodes of clinical hepatic encephalopathy. CONCLUSIONS: The prognostic significance of subclinical hepatic encephalopathy appears limited.

Adolescent↗
PubMed2000

A survey of liver pathology in needle biopsies from HBsAg and anti-HBe positive individuals.

AIMS: To use laboratory data and liver biopsies, prospectively obtained from hepatitis B surface antigen (HBsAg) and anti hepatitis B e antigen (anti-HBe) positive patients, for the assessment of: (1) the relation between biopsy length/number of portal tracts and sampling error; (2) the relation between the severity of piecemeal necrosis and the new grading terminology (minimal, mild, moderate, and severe chronic hepatitis); and (3) liver pathology, which has not been studied in patients with this specific serological profile. METHODS: The study group (n = 174) included 104 patients with normal aminotransferase concentrations and no cases with clinically apparent cirrhosis. The specimen length and number of portal tracts were measured at light microscopy examination. Sampling error analysis was related to the discrepancies between aminotransferase concentrations versus histological grade. Detailed histological scorings were undertaken by the reference pathologist and compared with laboratory and hepatitis B virus (HBV) DNA precore sequence data. RESULTS: Sampling error seemed to be a constant feature, even for biopsies > or = 20 mm, but increased dramatically in biopsies < 5 mm long and/or containing less than four portal tracts. Between 25% and 30% of biopsies, graded as "mild" or "moderate" activity showed features of moderate and severe piecemeal necrosis, respectively. Ten per cent of the patients with normal aminotransferase values had stage III-IV hepatic fibrosis, and 20% had piecemeal necrosis. Only cytoplasmic, not nuclear, core antigen expression was a strong predictor of high hepatitis B viraemia. There was no association between precore stop codon mutations, grade/stage of liver disease, and hepatitis B core antigen (HBcAg) expression. CONCLUSIONS: The specimen available for light microscopical examination should be > 5 mm long and should contain more than four portal tracts. In addition, the new grading terminology might give the clinician an inappropriately mild impression of the severity of piecemeal necrosis. Furthermore, even in the presence of normal aminotransferase concentrations, considerable liver pathology can be found in 10-20% of HBsAg and anti-HBe positive individuals; such pathology is not associated with the occurrence of precore stop codon mutations.

Biopsy, Needle↗
PubMed2000

Efficacy of influenza vaccination in adult liver transplant recipients.

To assess the efficacy of influenza vaccination in immunocompromised adult liver transplant (LTx) recipients, the serum antibody responses of 61 of these patients and 35 liver cirrhosis patients with those of 45 of their healthy spouses were compared, after one and two vaccinations with a commercial trivalent subunit influenza vaccine. In addition, virus-specific proliferative T-cell responses were measured in LTx recipients and their healthy spouses. In all three study groups, significant rises in geometric mean antibody titers were observed for all three antigens after one vaccination. These titers did not continue to increase significantly after the second vaccination in patients with cirrhosis and control subjects but did rise for LTx recipients. The overall antibody response to all three influenza virus strains proved to be significantly lower in the LTx recipients than in the group of healthy subjects after both one and two vaccinations. More than 68% of the LTx recipients developed hemagglutination-inhibiting serum antibody titers >/=40 against all three vaccine strains after the first vaccination and more than 80% after the second vaccination. These findings correlated with the T-cell responses determined for the group of LTx recipients and healthy control individuals. Testing of the respective serum samples against influenza virus A/Sydney/5/97, which circulated in the 1997-1998 influenza season and showed a considerable mismatch with the vaccine strain A/Nanchang/933/95, indicated that such a mismatch may have significant consequences for vaccine efficacy, especially for LTx recipients. Collectively the data show that LTx recipients can be vaccinated effectively against influenza despite immunosuppressive therapy. A two-dose vaccination regimen improved vaccination efficacy in LTx recipients. Whether transplant patients generally benefit from a two-dose vaccination regimen should be evaluated further.

Adult↗
PubMed2000

Contrasting patterns of response to lamivudine monotherapy in chronic hepatitis B patients.

In this paper we describe a cohort of patients treated with lamivudine, a reverse transcriptase inhibitor with a strong virus-suppressive effect on the hepatitis B virus. Eighty-nine patients were included in the intention-to-treat analysis. Evaluation with the Kaplan-Meier method was based on response to therapy of HBV DNA levels as well as normalization of transaminases. Subgroup evaluation based on the per protocol data was performed on two groups within this cohort based on the HBV DNA level at the end of therapy. During a 52-week treatment period, the chance of being HBV DNA negative at one point in time, as measured by the Digene Hybrid Capture assay (HCS) (limit of detection 1.5 x 10(6) geq/ml), the quantitative PCR assay (Q PCR) (limit of detection 1000 geq/ml), or the chance of normalization of transaminases at one point in time is 78%, 57% and 66%, respectively. Nineteen out of 73 patients who had continuing active viral replication after at least 24 weeks of lamivudine therapy were evaluated for the emergence of mutations resistant to lamivudine. In 3 out of 19 patients a mutation in the highly conservative YMDD region of the polymerase gene was detected. Baseline viral load in this group was significantly higher compared to the other 54 patients who were treated for 24 weeks or longer. Thirty-one out of 73 patients (46%) became negative by Q PCR. HBV DNA level at start of treatment was significantly lower compared to the 42 patients who remained HBV DNA positive. Eleven consecutive patients within this group who became negative by qualitative PCR (limit of detection 400 geq/ml) were evaluated to obtain characteristics for lamivudine withdrawal. Ten out of 11 patients became HBeAg negative with anti-HBe in 6. HBeAg in the liver biopsy was negative in 10 out of 11 patients; 9 out of 10 obtained biopsies were positive for HBV DNA, indicating low-level viral replication. In two patients in whom lamivudine was withdrawn, rebound of virus occurred. Further research is needed to obtain better insight into the variability in response. This might lead to a tailor-made individualized treatment regimen.

Adolescent↗
PubMed1999

[Two patients with acute hepatitis B from the same piercing salon].

Hepatitis B was diagnosed in two homosexual men aged 41 and 31 years. Both had undergone piercing on the same day in the same saloon. The word piercing means application of decorations in the skin which is pierced for the purpose. The breeching of the skin combined with the conditions under which this is performed leads to a risk of transmission of especially viral infections. An assumed connection between the patients was supported by the results of molecular-biological examination of the hepatitis B virus isolates. The piercings were applied with the same pair of pincers, which was not sterilized in between. In view of these findings hygienic measures were taken in the piercing saloon in question to prevent future transmission of infections. Piercing entails health risks that are not always recognized either by those who do it or by those who have it done.

Acute Disease↗
PubMed1999

[Chronic hepatitis-b-virus infections: new options for antiviral therapy].

The possibilities for antiviral treatment of patients with chronic hepatitis B virus (HBV) infections have been in flux for the last few years. Apart from interferon alpha, oral nucleoside analogues are given a place. The treatment focuses on the group of patients with active virus multiplication (hepatitis B e antigen (HBeAg) and HBV DNA are demonstrable), abnormal liver enzyme values and histologically demonstrated inflammatory activity in the liver. For the individual patient the pros and cons of protracted virus inhibition should be weighted by means of an orally administered nucleoside analogue such as lamivudine, immunostimulation with injections of interferon alpha or a combination of these two.

Antiviral Agents↗
PubMed1999

Antiviral treatment for human immunodeficiency virus patients co-infected with hepatitis B virus: combined effect for both infections, an obtainable goal?

A large percentage of human immunodeficiency virus (HIV) patients have serological evidence of a past or present hepatitis B virus infection (HBV). Long-term survival is increasing for HIV patients because of highly active antiretroviral therapy. Therefore, the chronic hepatitis B infection may become an important determinant of disease outcome in these co-infected patients. We describe two HIV/HBV co-infected patients who were treated with extended antiviral therapy, initially indicated for the HIV infection. Lamivudine, a suppressor of viral replication in both infections, was one of these antiviral drugs. One patient showed a severe rebound of the HBV after withdrawal of lamivudine, the other patient developed a mutant hepatitis B virus after 18 months of treatment. This mutation was exclusively induced by lamivudine. These patients show that, with improved HIV-related survival, the HBV infection should be monitored carefully, thereby enabling the physician to interfere with therapy when necessary.

Anti-HIV Agents↗
PubMed1998

[Hepatocellular adenoma in 20 patients; recommendations for treatment].

OBJECTIVE: Analysis of the diagnostic approach and management of 20 patients with hepatocellular adenoma, 1979-1996. SETTING: University Hospital Rotterdam-Dijkzigt, Rotterdam, the Netherlands. DESIGN: Retrospective and follow-up analysis. METHOD: Medical records of patients with histologically proven hepatocellular adenoma were analysed with respect to complaints, diagnostic approach and therapeutical management. Follow-up took place at the outpatient department where history-taking, physical examination, ultrasonography and hepatitis B and C serology tests were performed. RESULTS: In the period 1979-1996, 20 patients with hepatocellular adenoma were treated. Eight patients (mean tumour size 3.2 cm (1.5-5)) were treated conservatively, 12 (mean tumour size 8.1 cm (6-10)) underwent hepatic resection; four because of rupture of the tumour. Serum liver enzyme values did not contribute to the diagnosis. Of the lesions 78% were diagnosed correctly by ultrasonography and 71% by computer tomography. Median follow-up of the patients treated operatively was 73 months (1-204). One patient died three years after an incomplete resection of a hepatocellular adenoma, because of a hepatocellular carcinoma. Ultrasonography did not demonstrate any recurrent tumours in the other patients. In the group of patients conservatively treated (median follow-up 39 months (24-72)) two patients died because of a hepatocellular carcinoma. Ultrasonography demonstrated stable tumour diameters in three patients and regression in three others. CONCLUSION: Based on the literature and the presented experience surgical treatment is the treatment of choice in patients with large (> or = 5 cm diameter) hepatocellular adenomas because of the risk of malignant transformation and rupture of the tumour. With smaller tumours (< 5 cm) a conservative treatment may suffice in hepatitis virus negative patients, including withdrawal of oral contraceptives followed by thorough ultrasound follow-up of tumour size. In case of tumour growth or complaints a resection of the tumour is indicated.

Adenoma, Liver Cell↗
PubMed1998

[Major psychiatric side effects of interferon alpha-2b].

The Netherlands Pharmacovigilance Foundation Lareb and the Drug Safety Unit of the Inspectorate for Health Care in 1997 received 6 reports of serious psychiatric symptoms during the use of interferon alpha-2b. Of these patients, three men aged 42, 49 and 62 years and three women aged 31, 40 and 33 years, two had had psychic symptoms before. Depression or psychosis developed 12-24 weeks after the start of the use of interferon alpha-2b with 3-10 million IU per week subcutaneously because of chronic hepatitis B or C. After cessation of the medication, four patients recovered after a few days or weeks; the course of one patient was unknown, one patient had committed suicide. Knowledge of these psychiatric adverse drug reactions to interferon alpha-2b can contribute to early recognition by the physician and timely treatment of the symptoms.

Adult↗