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Biomedical subjects

H W Reesink

Publications and source records attributed to H W Reesink.

At least 73 records · Page 4Linked to original sources

Combination therapy with mycophenolate mofetil and ursodeoxycholic acid for primary biliary cirrhosis.

Evidence of autoimmunity in primary biliary cirrhosis (PBC) provides a rationale for treatment with an immunosuppressant. Such a drug should be sufficiently free from serious toxicities to enable patients with asymptomatic, but progressive, disease to be treated longterm. Mycophenolate mofetil (MMF) mediates immunosuppression by selectively and reversibly inhibiting lymphocyte function, and has a more acceptable safety profile than other immunosuppressants that have been used in the treatment of this disease. Two patients, whose response to long-term treatment with ursodeoxycholic acid (UDCA) had been inadequate, were treated with a combination of MMF 2 g daily and UDCA 1 g daily for 12 months. In both patients this regimen was associated with no clinically significant adverse events, a decrease in elevated serum alkaline phosphatase levels to values close to the upper limit of normal, and an almost complete disappearance of the chronic inflammatory cell infiltrate that had been present in pre-combination treatment liver biopsies. MMF may be an appropriate immunosuppressive drug for use in the long-term treatment of patients with PBC, including asymptomatic patients.

Alkaline Phosphatase↗

[The management of acute hepatitis C and needlestick accidents with hepatitis-C virus positive blood].

Acute hepatitis C is rarely diagnosed, in part because of its usually subclinical course. Infection with the hepatitis C virus (HCV) has a high chronicity rate, 70-90%. The risk of infection after a needlestick accident with HCV positive blood is 3-10%. There are no efficacious preventive measures regarding HCV infection but treatment with the antiviral drug interferon alpha during the acute phase of the disease has shown to significantly reduce the risk of subsequent chronic infection. It is advised to evaluate individuals who were exposed to infected blood by a needlestick accident regarding HCV transmission, and to offer interferon treatment to them in case they become HCV positive, as demonstrated with a positive serum HCV-RNA test.

Disease Transmission, Infectious↗

Relation between laboratory test results and histological hepatitis activity in individuals positive for hepatitis B surface antigen and antibodies to hepatitis B e antigen.

BACKGROUND: Hepatitis B surface antigen (HBsAg) and antibodies to hepatitis B e antigen (anti-HBe) commonly coexist, and laboratory tests are often requested to assess histological hepatitis activity. An optimum panel of tests has not been found and the usefulness of hepatitis B virus (HBV) DNA assays in this context has not been established. We assessed various blood tests to find which best predicted hepatitis activity. METHODS: Routine plasma biochemical liver tests and serum HBV DNA (hybridisation and PCR assays) were assessed prospectively in 123 patients positive for HBsAg and anti-HBe. We scored histological hepatitis activity (hepatitis activity index) and determined whether chronic active hepatitis (chronic hepatitis with portal and periportal lesions) was present. We analysed the relation between laboratory data and the hepatitis activity index or risk of chronic active hepatitis by multiple regression and multiple logistic regression, respectively. FINDINGS: The analyses provided models for predicting either the hepatitis activity index or the risk of chronic active hepatitis. Aspartate aminotransferase was the most important test in the two models. The contribution of HBV DNA and other assays, especially alanine-aminotransferase activity, were of no practical importance. INTERPRETATION: Because screening by aspartate-aminotransferase activity could not be improved by the addition of other assays or HBV DNA, patients positive for HBsAg and anti-HBe could be screened for chronic active hepatitis with a single assay and counselling of patients can be improved if proper reference values are used.

Adult↗

[Optimal versus maximal safety of the blood transfusion chain in The Netherlands; results of a conference. College for Blood Transfusion of the Dutch Red Cross].

An invitational conference was held on September 11, 1996 by the Medical Advisory Commission to the Blood Transfusion Council of the Netherlands Red Cross, addressing the issues of 'maximal' versus 'optimal' safety measures for the blood supply. Invited were blood transfusion specialists, clinicians, representatives of patient interest groups, the Ministry and Inspectorate of Health and members of parliament. Transfusion experts and clinicians were found to advocate an optimal course, following strategies of evidence-based medicine, cost-benefit analyses and medical technology assessment. Patient groups depending on blood products, such as haemophilia patients would rather opt for maximal safety. Insurance companies would choose likewise, to exclude any risk if possible. Health care juridical advisers would advise to choose for optimal safety, but to reserve funds covering the differences with 'maximal safety' in case of litigation. Politicians and the general public would sooner choose for maximal rather than optimal security. The overall impression persists that however small the statistical risk may be, in the eyes of many it is unacceptable. This view is very stubborn.

Blood Transfusion↗

Stability of hepatitis C virus RNA during specimen handling and storage prior to NASBA amplification.

The influence of different anticoagulants and pre-amplification storage conditions on the stability of hepatitis C virus (HCV)-RNA, as detected by the quantitative HCV NASBA assay (NASBA-QT), was studied. The HCV-RNA load remained stable for at least 15 months when serum or plasma samples (EDTA and heparin) were directly frozen at -70 degrees C in lysis buffer. At 4 degrees C, the HCV-RNA load in serum or plasma stored with lysis buffer did not decline for at least 14 days. At 30 degrees C, however, the load declined significantly after 7 days. When clotted, whole blood was stored at 4 degrees C, the HCV-RNA load was stable for 72 h. However, when EDTA-anticoagulated whole blood was stored at 4 degrees C, the HCV-RNA load declined significantly after 48 h. In paired plasma and serum samples at baseline the HCV-RNA levels were similar. Heparin did not influence the efficiency of the HCV NASBA-QT assay. Clotted blood as well as EDTA or heparin anticoagulated blood can be used for quantifying HCV-RNA using the NASBA-QT assay. Blood samples should be stored at 4 degrees C after collection and serum or plasma separated within 24 h. Preferably, after separation, samples should be frozen in lysis buffer at -70 degrees C until NASBA-QT analysis.

Buffers↗

Transfusion-transmissible infections.

Infectious agents, including viruses, bacteria, and parasites, can be transmitted by human blood products. Of major importance are viruses such as human immunodeficiency virus types 1 and 2 (HIV-1/2), hepatitis B virus (HBV), hepatitis C virus (HCV), and human T-cell lymphotropic virus types I and II (HTLV-I/II). Also, other viruses such as cytomegalovirus, Epstein-Barr virus, human parvovirus B19, and hepatitis A and G viruses can be transmitted by blood products. Various methods are used to prevent transmission of blood-borne agents to recipients, such as donor selection, testing donated blood for various infectious agents, and viral inactivation of plasma derivatives. With all these precautionary measures, the estimated risk for infection by screened blood components in Europe and the United States is approximately 1 in 50,000 to 1.6 million (for HBV, HCV, and HIV-1/2) transfused blood components. In the future, the safety of blood components may be increased by testing donated blood by nucleic acid amplification techniques and by photochemical decontamination of cellular blood components.

Bacterial Infections↗

Donor selection: the exclusion of high risk donors?

Selection of donors is an important means to improve the overall safety of the blood supply. Since the AIDS epidemic emerged and after the introduction of sensitive screening tests for HIV, it became clear that blood donations given in the infectious 'window' period, formed the most important risk for recipients of blood products. Therefore, selection criteria became more and more stringent to exclude these high risk donors. Means to exclude high risk donors are non-remuneration, including a clear policy to provide no incentives which can be readily converted to cash, the avoidance of replacement donations, the discouragement of 'HIV test seeking' donors, education and information of donors about HIV and other blood-borne infectious diseases and the in depth questioning about risk behaviour, orally as well as by questionnaires. Although this policy of donor selection is recognized by most blood centers in the world, the efficacy of this selection has not been well documented. Therefore in future, studies should be performed to base these selection criteria on evidence.

AIDS Serodiagnosis↗

Evaluation of a new HTLV-I/II polymerase chain reaction.

AIM: Evaluation of a qualitative HTLV-I/II DNA polymerase chain reaction (PCR) test for the detection of HTLV-I/II DNA (Roche Diagnostic Systems, Branchburg, N.J., USA) in various panels. METHODS: The panels consisted of fresh EDTA blood samples from blood donors who were anti-HTLV-I/II ELISA repeatably reactive: 53 were Western blot (WB) positive, 228 were WB indeterminate and 15 were WB negative. Elevent ELISA-negative blood donors were used as negative controls. Furthermore, specimens from 1 HTLV-II-infected intravenous drug user and from 1 HTLV-II-infected blood donor were included in the panel. Peripheral blood lymphocytes were prepared by red blood cell lysis with the Roche washing solution and stored at < -23 degrees C until processing. Amplification products were analyzed with the HTLV-I/II detection kit. RESULTS: All 53 anti-HTLV-I/II ELISA- and WB-positive samples and both HTLV-II-positive samples tested positively by PCR. All 228 anti-HTLV-I/II ELISA-positive and WB-indeterminate, all 15 ELISA-positive and WB-negative and all II ELISA-negative control samples tested negative by PCR. CONCLUSION: The Roche Amplicor HTLV-I/II test is a simple test, suitable for the confirmation of HTLV-I and-II infection in individuals with indeterminate or positive WB patterns.

Blood Donors↗

Performance of three generations of anti-hepatitis C virus enzyme-linked immunosorbent assays in donors and patients.

BACKGROUND: Prevention of posttransfusion non-A,non-B hepatitis in recipients of blood components improved considerably with the introduction of the second-generation of hepatitis C virus (HCV) antibody tests. In 1993, third-generation HCV antibody assays were introduced in Europe. STUDY DESIGN AND METHODS: The performance of three generations of anti-HCV enzyme-linked immunosorbent assay (ELISA) (ELISA-1, -2, -3) was compared in routine blood donor screening (99,394 donations were tested with ELISA-1, 167,999 donations with ELISA-2, and 262,090 donations with ELISA-3) and in serial samples from nine patients with documented acute posttransfusion HCV infection. RESULTS: Eight (0.01%) repeat donors, previously negative in ELISA-1, were found positive in ELISA-2 and were confirmed as positive in second-generation recombinant immunoblot assay and/or cDNA polymerase chain reaction. In the donor population, no difference in the sensitivity of ELISA-2 and -3 was observed. The specificity of the three generations of ELISAs was comparable (99.8, 99.7, and 99.7%). In seroconversion samples, ELISA-2 and -3 detected HCV antibodies at the same time in seven patients, but in two patients, ELISA-3 found HCV antibodies, respectively, 63 and 77 days earlier than ELISA-2 did. In the seroconversion samples, ELISA-2 and -3 were significantly more sensitive than second- and third-generation recombinant immunoblot assays. CONCLUSION: ELISA-3 did not detect more HCV-infected individuals in a donor population that previously tested negative in ELISA-2, but it did detect HCV antibodies earlier in some patients with acute HCV infection. ELISA-2 and -3 were significantly more sensitive than second- and third-generation recombinant immunoblot assays.

Blood Donors↗

Formation of antibodies to factor VIII in patients with hemophilia A who are treated with interferon for chronic hepatitis C.

OBJECTIVE: To evaluate the risk for development of antibodies to factor VIII (factor VIII inhibitors) during and after interferon therapy in patients with hemophilia A and chronic hepatitis C infection. DESIGN: Patients were divided into two treatment groups and an untreated control group. Test results from the two treatment groups were compared with those from the control group. SETTING: 3 clinical centers in the Netherlands. PATIENTS: 35 men with hemophilia A who had acquired hepatitis C through the use of plasma-derived clotting factor concentrates. MEASUREMENTS: Patients were tested for factor VIII inhibitors before the start of interferon therapy and every 6 months thereafter. RESULTS: 21 patients with hemophilia A received interferon therapy for chronic hepatitis C infection for a mean of 19.5 months (range, 0.5 to 36 months). In 2 patients, inhibitors were detected on one occasion (maximum titer, 1.2 Bethesda units/mL) during interferon therapy. In 3 patients who were known to have had inhibitors before interferon therapy, no anamnestic reaction was seen during treatment. In 3 of 14 untreated controls who were followed for a mean of 28 months (range, 18 to 40 months), inhibitors were detected on one occasion (maximum titer, 2.3 Bethesda units/mL). CONCLUSION: Long-term interferon therapy in patients with hemophilia did not increase the risk for development of factor VIII inhibitors.

Antibody Formation↗

International collaborative study on the second EUROHEP HCV-RNA reference panel.

Eighty-six laboratories participated in a collaborative study and tested the second EUROHEP HCV-RNA reference panel. The coded panel comprised 4 HCV-RNA positive plasma samples (one weak positive), 6 HCV-RNA negative plasma samples and two dilution series of HCV-RNA genotype 1 and 3 plasma standards. The 86 laboratories submitted 136 coded data forms for evaluation. Of these data sets 99 were tested using a PCR assay developed in-house, 28 using a commercially available HCV-PCR test (AMPLICOR, Roche Diagnostic Systems) and 9 using other amplification methods. Twenty-two data forms (16%) had faultless results, 39 (29%) missed the weak positive sample only and 75 data sets (55%) had false positive and/or false negative results. Participants using the commercial HCV-PCR test tended to reach a sufficient quality score more often than investigators using assays developed in-house (64% versus 45%, P = 0.11). The UNG system in the commercial HCV-PCR test did not prevent five laboratories generating false-positive results in the 6 HCV-RNA negative samples. Among the laboratories with satisfactory results, up to 10000-fold differences in sensitivity were observed in the dilution series. The 50% and 90% laboratories detection endpoints in the dilution series of the HCV genotype 1 plasma standard were approximately 600 genome equivalents per ml (geq/ml) and 7750 geq/ml according to a standard applied in a signal amplification assay (bDNA, Chiron). Our results suggest that the detection efficiency for genotype 3 by commercial HCV-RNA assays is lower than by the in-house assays. Internationally characterized HCV-RNA plasma standards should be made available for validation and standardization of HCV-RNA assays for HCV diagnosis and virological safety testing of blood products.

Hepacivirus↗

Sensitivity and specificity of four assays to detect human T-lymphotropic virus type I or type I/II antibodies.

BACKGROUND: Assays that detect human T-lymphotropic virus type I and type II antibody (HTLV-I/II) are widely used in the routine screening of blood donors. STUDY DESIGN AND METHODS: Four commercially available anti-HTLV-I (Fujirebio and Organon Teknika) or -HTLV-I/II assays (Murex and Ortho) were evaluated in various serum panels: A) HTLV-I-positive specimens (n = 41), confirmed by Western blot and polymerase chain reaction; B) a commercially available anti-HTLV-I/II panel; C) serial dilutions of sera from HTLV-I-positive individuals (n = 30), confirmed by immunofluorescence assay and Western blot: D) serial dilutions of HTLV-II-positive blood donors (n = 20), confirmed by Western blot and polymerase chain reaction, and E) sera from first-time blood donors (n = 1055). RESULTS: All four assays elicited reactions in all 82 HTLV-I-positive samples in Panels A, B, and C. Of 32 HTLV-II-positive specimens in Panels B and D, 31 (96.9%) reacted in the Organon Teknika assay and all 32 reacted in the remaining tests. Probit analysis of test results in Panels C and D indicated that the Fujirebio test was the most sensitive assay, followed by Organon Teknika, Ortho, and Murex. The specificities of Fujirebio, Murex, Organon Teknika, and Ortho tests in 1055 first-time blood donors were 99.9, 100, 99.6, and 99.9 percent, respectively. CONCLUSION: All four studied assays for detecting HTLV-I or HTLV-I/II antibodies are appropriate as screening tests.

Blood Donors↗