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Biomedical subjects

C H ten Napel

Publications and source records attributed to C H ten Napel.

At least 19 recordsLinked to original sources
PubMed1999

Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy. INCAS Study Group.

BACKGROUND: Current antiretroviral treatment can induce significant and sustained virological and immunological responses in HIV-1-infected persons over at least the short- to mid-term. OBJECTIVES: In this study, long-term immune reconstitution was investigated during highly active antiretroviral therapy. METHODS: Patients enrolled in the INCAS study in The Netherlands were treated for 102 weeks (range 52-144 weeks) with nevirapine (NVP) + zidovudine (ZDV) (n = 9), didanosine (ddl) + ZDV (n = 10), or NVP + ddl + ZDV (n = 10). Memory and naïve CD4+ and CD8+ T cells were measured using CD45RA and CD27 monoclonal antibodies (mAb), T-cell function was assayed by CD3 + CD28 mAb stimulation, and plasma HIV-1 RNA load was measured by ultra-direct assay (cut-off < 20 copies/ml). RESULTS: Compared to both double combination regimens the triple combination regimen resulted in the most sustained increase in CD4+ T cells (change in CD4+, + 253 x 10(6) cells/l; standard error, 79 x 10(6) cells/l) and reduction of plasma HIV-1 RNA. In nine patients (31%) (ddl + ZDV, n = 2; NVP + ddl + ZDV, n = 7) plasma HIV-1 RNA levels remained below cut-off for at least 2 years. On average, these long-term virological responders demonstrated a significantly higher increase of naïve and memory CD4+ T cells (P = 0.01 and 0.02, respectively) as compared with patients with a virological failure, and showed improved T-cell function and normalization of the naïve; memory CD8+ T-cell ratio. However, individual virological success or failure did not predict the degree of immunological response. T-cell patterns were independent of baseline CD4+ T-cell count, T-cell function, HIV-1 RNA load or age. Low numbers of naïve CD4+ T cells at baseline resulted in modest long-term naïve T-cell recovery. CONCLUSIONS: Patients with prolonged undetectable plasma HIV-1 RNA levels during antiretroviral therapy do not invariably show immune restoration. Naïve T-cell recovery in the setting of complete viral suppression is a gradual process, similar to that reported for immune recovery in adults after chemotherapy and bone marrow transplantation.

Adult↗
PubMed1996

Treatment of the Budd-Chiari syndrome by insertion of a wall-stent in the hepatic vein after percutaneous transluminal angioplasty: the necessity of follow-up.

Budd-Chiari syndrome is a rare disease and, with or without treatment, the prognosis is usually poor. Percutaneous transluminal angioplasty of the hepatic vein in Budd-Chiari syndrome is a safe method, although recurrent stenosis makes it necessary to repeat it several times in most cases. Insertion of a wall-stent in the hepatic vein seems to be a more long-lasting treatment. Monitoring the blood flow through the wall-stent every 6 months is important because of the apparent obliteration of the wall-stent by intimal fibrosis of the hepatic vein. Further follow-up investigations of this method are necessary.

Angioplasty, Balloon↗
PubMed1995

Treatment of poor prognosis epidemic Kaposi's sarcoma with doxorubicin, bleomycin, vindesine and recombinant human granulocyte-monocyte colony stimulating factor (rh GM-CSF).

The efficacy and toxicity of doxorubicin, bleomycin and vindesine in epidemic Kaposi's sarcoma, and the role of rh GM-CSF in chemotherapy-induced neutropenia were evaluated in this Phase II study. Patients with progressive Kaposi's sarcoma were eligible, and were staged according to ACTG criteria. Treatment consisted of 20 mg/m2 doxorubicin, and a fixed dose of 15 mg bleomycin and 4 mg vindesine every 2 weeks. All patients continued antiretroviral medication with severe myelosuppression, patients received subcutaneous 5 micrograms/kg rh GM-CSF (Leucomax) from days 2-12. Response and toxicity were measured according to ACTG and WHO criteria. 27 patients were evaluable, 25 patients classified as having a poor prognosis. The response rate was 70% (3 CR, 16 PR), the duration of response was 18 weeks (range 8-25) and the median survival 30 weeks (range 4-63+). The cause of death was mostly opportunistic infection. 4 patients died of pulmonary Kaposi's sarcoma. The toxicity of this regimen was mainly myelosuppression and 13 patients were treated with rh GM-CSF. Complete recovery of the white blood cells occurred in seven of the 27 courses of rh GM-CSF (26%). No bacterial infections were recorded, but 5 patients (19%) developed an opportunistic infection during treatment. Peripheral neuropathy occurred in 16% of patients. Combination chemotherapy is effective in poor prognosis Kaposi's sarcoma but has a shortlasting effect. The main toxicity of this treatment is severe myelosuppression which can be ameliorated by rh GM-CSF. It remains to be established whether rh GM-CSF is also able to reduce the incidence of opportunistic infections.

Adult↗
PubMed1994

Clinical, toxicological and pharmaceutical aspects of the antineoplastic drug taxol: a review.

Taxol, a diterpene alkaloid isolated from the bark of Taxus brevifolia, has a unique mechanism of action. The drug promotes the formation of microtubule polymers in a cell, by reversibly and specifically binding the beta-subunit of tubulin. Taxol is administered intravenously by a 3-24-hour infusion at 3-week intervals. Myelosuppression, especially neutropenia, appears to be the dose limiting toxicity in solid tumours at 200-250 mg/m2. Furthermore, side effects such as sensory neurotoxicity (with typical numbness, tingling and painful paraesthesiae in the extremities), diarrhoea and alopecia appear frequently. Mucositis appears to be the non-haematological dose limiting side effect at 390 mg/m2 that has been determined in patients with leukaemia. Hypersensitivity reactions, which have been fatal in individual cases, might be schedule dependent. Furthermore, antiallergic prophylaxis must be given, although this precaution might not be considered to be fully protective. Phase I studies performed with combinations of taxol and cisplatin, doxorubicin or cyclophosphamide have indicated the feasibility of these regimens and show promise for future investigations. Addition of granulocyte-colony stimulating factor (G-CSF), aimed at modulating myelosuppressive toxicity, showed in Phase I studies that the taxol dose could be increased to 250 mg/m2, with peripheral neuropathy as the dose limiting toxicity. In Phase II studies, taxol has been shown to be effective, including producing complete tumour remission, in advanced drug refractory ovarian carcinoma (19%-36% response rate), previously treated patients with metastatic breast carcinoma (27%-62% response rate), advanced non-small lung cancer (21%-24% response rate), advanced small cell lung cancer (37% response rate) and advanced head and neck cancer (34% response rate).(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Zidovudine and interferon-alpha combination therapy versus zidovudine monotherapy in subjects with symptomatic human immunodeficiency virus type 1 infection.

Forty-five subjects with symptomatic human immunodeficiency virus type 1 (HIV-1) infection, CD4+ lymphocyte counts of > or = 150 x 10(6)/L, and Karnofsky scores > or = 60 were enrolled in a multicenter, randomized, controlled trial that compared zidovudine monotherapy and combination therapy for 48 weeks with zidovudine and interferon-alpha (IFN-alpha). Zidovudine with IFN-alpha (n = 25) had a favorable effect on CD4+ cell counts compared with zidovudine alone (n = 20). At all time points analyzed, the mean change from baseline was higher, reaching significance at week 24 (+10% versus -21%; P = .029). At week 48 the difference was -12% versus -45% (P = .07). Anti-CD3 monoclonal antibody-induced T cell reactivity improved temporarily in both groups. Serum HIV p24 antigen levels decreased maximally during the first 12 weeks of treatment. At weeks 0 and 48, polymerase chain reaction analysis for mutations at codons 67 and 215 of the HIV-1 reverse transcriptase gene conferring zidovudine resistance was conducted in 10 subjects receiving zidovudine and in 8 subjects receiving combination therapy. At week 48, 1 of 8 and 4 of 6 samples from the groups receiving zidovudine only or combination therapy, respectively, contained wild type virus at codon 215. Grade 3 or 4 toxicity was uncommon. Drug-related malaise and anorexia were observed more frequently in patients receiving both zidovudine and IFN-alpha.

Adult↗
PubMed1994

Pharmacokinetic variability of zidovudine in HIV-infected individuals: subgroup analysis and drug interactions.

OBJECTIVE: To investigate determinants of inter- and intraindividual variability of zidovudine (ZDV) pharmacokinetics in HIV-infected patients. DESIGN: A prospective study in a general 525-bed hospital with special funding for treatment and research of HIV-infected patients. METHODS: Serial blood samples were collected from 68 HIV-infected individuals providing a total of 95 pharmacokinetic curves. ZDV was measured with high-performance liquid chromatography and radioimmunoassay. Pharmacokinetic parameters were calculated by non-compartmental analysis. Patient characteristics were investigated by multivariate analysis for an influence on ZDV pharmacokinetics. RESULTS: Apparent ZDV clearance was significantly lower in patients with a lower body weight, in women, and in patients with a more advanced stage of HIV disease. Co-administration of methadone with ZDV resulted in higher plasma concentrations of ZDV, while rifampin and ganciclovir increased apparent ZDV clearance. Age, the duration of ZDV use, CD4+ cell count, creatinine clearance, elevated serum liver enzyme levels, and the use of 11 other co-administered medications were not independently related to apparent ZDV clearance. CONCLUSIONS: The pharmacokinetic profile of ZDV in several subpopulations has been evaluated, as well as the observation of possible drug-drug interactions between ZDV and 14 different drugs or groups of drugs. These data suggest that patient-individualized antiretroviral therapy may be appropriate once pharmacokinetic-pharmacodynamic relationships have been established.

Adult↗
PubMed1994

Application of a radioimmunoassay for determination of levels of zalcitabine (ddC) in human plasma, urine, and cerebrospinal fluid.

A specific and sensitive radioimmunoassay for the determination of levels of zalcitabine in human plasma, urine, and cerebrospinal fluid has been developed. Commercially available radiolabel and antiserum (Sigma Chemicals) were used after dilution in assay buffer. Prior to the immunoassay, standard and patient samples were subjected to solid-phase extraction on silica columns in order to obtain purified samples. The lower limit of quantitation was determined to be 1 ng/ml. Intra- and interassay variations were less than 11% for a number of quality control samples of drug in plasma and urine. Results from parallelism studies with plasma and urine demonstrated that samples outside the standard range (1 to 30 ng/ml) could be diluted by blank plasma or assay buffer, respectively. A large number of related compounds and potentially coadministered drugs were tested for cross-reactivity. Stability tests showed that heat treatment for 30 min at 60 degrees C or storage for 1 month at -30 degrees C did not affect zalcitabine concentrations in plasma or urine. The radioimmunoassay with solid-phase extraction for sample cleanup discussed here has been successfully applied in a pharmacokinetic study of a single patient, demonstrating its applicability for clinical pharmacokinetic research with zalcitabine.

Humans↗
PubMed1993

[A man with spontaneous regression of non-Hodgkin lymphoma, hypergammaglobulinemia and infection caused by 2 herpesviruses; causality or coincidence?].

A febrile illness with atypical peripheral blood lymphocytosis (polyclonal CD8+ suppressor/cytotoxic phenotype), complement activation and IgA/G class hypergammaglobulinaemia was found in a 76-year old male with clinical stage III follicular non-Hodgkin lymphoma (NHL). There was serological evidence of active cytomegalovirus (CMV) as well as reactivated chronic Epstein-Barr virus (EBV) infection. Spontaneous regression of NHL appeared, the signs of viral infection improved but hypergammaglobulinaemia persisted. In patients with malignant lymphoma, clinical signs and abnormalities of peripheral blood lymphocytes and serum immunoglobulins should not automatically be considered a consequence of the lymphoma.

Aged↗
PubMed1992

[Doctor's delay in HIV infection caused by blood transfusion].

Transfusion-associated symptomatic HIV infection in four patients led to death in two patients and to development of serious neurological sequelae in a third patient who also transmitted HIV infection to his spouse. The tardy diagnosis of HIV-associated disease in all cases can be ascribed to ignoring the earlier blood transfusion as a possible cause of HIV infection. This was due partly to advanced age of the patients and partly to lack of familiarity of the attending physicians with HIV-associated problems. This resulted in a substantial doctor's delay.

AIDS Serodiagnosis↗
PubMed1992

Kikuchi's lymphadenitis: report of a Yersinia enterocolitica-associated case and an overview of aetiology and clinical outcome.

Kikuchi's lymphadenitis (KL; histiocytic necrotizing lymphadenitis without granulocytic infiltration) is a generally benign, febrile disorder of unknown aetiology with distinct histological features. To date, a minority of cases reported have been associated with infectious agents. A typical pathological case of KL is described where involvement of Yersinia enterocolitica was shown by an indirect immunofluorescent assay applied to lymphatic tissue. The case is discussed with emphasis on recent insight into the course and aetiology of KL.

Adult↗
PubMed1992

Common variable immunodeficiency in a family.

Common variable immunodeficiency (CVID) is mainly characterised by hypo- or agammaglobulinaemia of late onset, usually discovered in the second decade of life. In individuals CVID is associated with a variable impairment of cellular immunity and the susceptibility to microbial infection may vary as well. CVID is described in a mother and a son who suffered from serious bacterial infections. In addition, minor immunological test abnormalities of apparently healthy first degree relatives are described.

Adult↗
PubMed1989

[A patient with familial Mediterranean fever].

Familial Mediterranean fever, a genetic disorder with an autosomal recessive pattern of inheritance, occurs in patients originating from the eastern Mediterranean. Characteristic features are attacks of fever, peritonitis, pleuritis, synovitis and skin rash. The disease may be complicated by amyloidosis. Treatment with colchicine is generally successful.

Abdomen, Acute↗
PubMed1989

[Transient bone marrow inhibition caused by aminoglutethimide].

A 53-year-old woman with reversible bone marrow insufficiency caused by aminoglutethimide (AGT) treatment of metastatic breast carcinoma is described. The clinical picture included moderate thrombocytopenia and severe granulocytopenia complicated by Gram-positive septicaemia and skin infections, and by oral candidiasis. Withdrawal of AGT and antibiotic therapy resulted in clinical and haematological recovery, but the patient died suddenly, probably from a cardiac cause. Autopsy revealed widespread bone metastases, but no bone marrow infiltration of breast carcinoma. The haematological hazards caused by application of AGT are discussed.

Adenocarcinoma↗