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Biomedical subjects

D Schrijvers

Publications and source records attributed to D Schrijvers.

At least 55 records · Page 3Linked to original sources
PubMed1995

Phase I and pharmacokinetic study of a novel mitomycin C analog KW-2149.

KW-2149 is a new, semisynthetic, C-7-N-substituted, mitomycin C (MMC) analog showing equal or superior antitumor activity in both in vitro and in vivo assays. The preclinical activity profile combined with the hematological toxicity data in rodents and the water solubility of the compound compare favorably with MMC. The aim of this phase I study was to determine the toxicity profile and the optimal dosage of KW-2149. In this phase I study 37 patients received 97 courses of KW-2149 administered as an i.v. bolus injection every 21 days at sequential dose levels: 5, 10, 17, 25, 35, 47, 60, 75, 90 and 100 mg/m2. Hematological toxicity was moderate even at the 100 mg/m2 dose level. Grade IV leucopenia and thrombocytopenia were observed in one of three patients at the 100 mg/m2 dose level. There was some evidence of a delayed-type bone marrow toxicity. Pulmonary toxicity was dose limiting, with grade III toxicity occurring in all three patients treated at a dose of 100 mg/m2. The type of lung toxicity was similar to the one observed with other antitumor antibiotics. No renal or cardiac toxicity was observed. Other toxicities were generally mild. Antitumor activity was observed in four patients. Data of drug monitoring demonstrated rapid metabolism and/or distribution of KW-2149 with a short half-life and the emergence of the cytotoxic metabolites M-16 and M-18. The dose-limiting toxicity of KW-2149 is pulmonary toxicity.

Adenocarcinoma↗
PubMed1995

Docetaxel (Taxotere), a review of preclinical and clinical experience. Part II: Clinical experience.

Docetaxel, a promising inhibitor of microtubule depolymerization has shown significant anti-cancer activity during phase I and early phase II trials. The recommended dosage for phase II trials is 100 mg/m2 every 3 weeks which provides optimal activity with tolerable adverse effects. Docetaxel has shown high single agent activity including use as first- or second-line therapy and in anthracycline refractory breast cancer patients. Results have been comparable to that of established treatments for breast cancer. In addition, docetaxel has shown significant activity in non-small cell lung cancer and a range of other tumors, but no activity in renal or colo-rectal tumors. At present it is undergoing further evaluation in combination therapy. The safety profile of docetaxel is well defined. Major adverse effects include hypersensitivity reactions, fluid retention and neutropenia. Peripheral neuropathy is not a significant adverse effect. The aims of phase II trials with regard to counteracting side-effects are therefore 2-fold: firstly, to evaluate the use of premedication with corticosteroids and antihistamines as a means of counteracting hypersensitivity reactions and fluid retention; secondly, to determine whether granulocyte colony stimulating factor may be useful for attenuating neutropenia.

Antineoplastic Agents↗
PubMed1994

Demographic factors associated with HTLV-1 infection in a Gabonese community.

An epidemiological study of human T-lymphotropic virus type 1 (HTLV-1) and syphilis has been carried out in a multiethnic community of seven neighbouring villages located in eastern Gabon on 1240 subjects over 5 years old (82.7% of the population in this age range). Antibodies to HTLV-1 (anti-HTLV-1) were detected by ELISA with confirmation by Western Blot and antibodies to syphilis by Venereal Diseases Research Laboratory assay with confirmation by the Treponema pallidum haemaglutination assay. The prevalence rate of anti-HTLV-1 was 8.5% and increased from 3.7% in the 5-14 years age group to 23.8% in the over 60 years age group. Logistic regression showed that the positivity for anti-HTLV-1 was associated with age, ethnic group and sex (higher prevalence in females). The seroprevalence rate of syphilis was 8.2%. Seropositivity for syphilis and HTLV-1 were related but age was a confounding variable in this relationship. This study showing a highly heterogeneous distribution of HTLV-1 in a geographically limited area suggests the role of environmental and behavioural factors in HTLV-1 transmission.

Adolescent↗
PubMed1994

A phase II trial of dose-escalated doxorubicin and ifosfamide/mesna in patients with malignant mesothelioma.

BACKGROUND: This study investigated the feasibility and efficacy of doxorubicin dose-escalated chemotherapy in combination with ifosfamide in patients with malignant mesothelioma. PATIENTS AND METHODS: In this single institution phase II study, 24 chemotherapy-naive, eligible patients were entered. The chemotherapy regimen consisted of doxorubicin 75 mg/m2 in combination with ifosfamide 5 gr/m2 given as a continuous 24 hour infusion, every 21 days with either rhG-CSF (5 micrograms/kg) or rhGM-CSF (250 micrograms/m2) as haematopoietic support from d3 to d14. Cycles were repeated every 3 weeks. RESULTS: We treated 24 patients, of whom 22 are evaluable for tumour response. One of the two inevaluable patients died from a cerebral haemorrhage during a period of grade III thrombocytopenia after the second course. In 7 patients a partial response was observed, resulting in a response rate of 32% (95% confidence interval 13%-51%). Median response duration was 6 months (range 1-13) and median survival was 7 months (range 1-18). CONCLUSIONS: The high-dose regimen with growth factor support is feasible in this group of patients and leads to an interesting response rate. The limiting toxicity for further dose increments and more courses of treatment, was cumulative thrombocytopenia. There seems to be a subgroup of patients with malignant mesothelioma which is less susceptible to develop thrombocytopenia. However, the overall toxicity and the poor response duration limit the use of this schedule in the treatment of malignant mesothelioma.

Adult↗
PubMed1993

Coping with toxicities of docetaxel (Taxotere).

BACKGROUND: In phase II studies of the EORTC-ECTG, acute hypersensitivity reaction, edema and skin toxicity were important side effects of docetaxel (TaxotereTM). PATIENTS AND METHODS: Fifty patients with solid tumors were treated with docetaxel at the University Hospital of Antwerp. Of these, 28% developed an acute hypersensitivity reaction and 20% edema. Twelve and three hours before the next docetaxel administrations those with the acute hypersensitivity reaction were subsequently pretreated orally with 32 mg of methylprednisolone, 10 mg of cetirizine and 1 mg of ketotifen. CONCLUSIONS: The acute hypersensitivity reaction could be completely blocked in all but in 1 of 14 patients, and this pretreatment schedule had an important prophylactic effect on edema formation. Skin toxicity was successfully treated with an ointment of glycerin and chlorhexidine.

Antineoplastic Agents, Phytogenic↗
PubMed1991

In vivo decreased expression of CD25 (p55 chain of IL-2 receptor) on CD3+ T cells correlates with low in vitro responsiveness to Plasmodium falciparum antigen in subjects living in a malaria endemic area.

Significant proliferative responses of peripheral blood mononuclear cells (PBMC) to crude Plasmodium falciparum schizont antigen (M.Ag) or purified recombinant 31.1 Ag (part of gp 195) were observed only in 46 and 39%, respectively, of 50 healthy subjects 5 to 63 years old living in Gabon, a malaria-endemic area. High responses to pokeweed mitogen were observed in all the subjects except one. Interferon-gamma (IFN-gamma) production paralleled the proliferative response, but in some subjects proliferation without a IFN-gamma response was observed. The proportion of subjects responding to M.Ag and 31.1 Ag increased with age. By cytofluorometric analysis performed with PBMC from 27 subjects, a substantial proportion of CD3+ T cells was found to bear the activation marker HLA-DR. However, the CD3+ cells expressed very low levels of CD25 (p55 chain of IL-2 receptor). The expression of CD25 on T cells and their capacity to respond to M.Ag were significantly correlated. In four subjects an increase in the percentage of CD3+ cells bearing the very late activation marker VLA-1 was observed.

Adolescent↗
PubMed1991

Pulmonary aspergillosis complicated by osteomyelitis.

We report on a patient with aplastic anaemia and an invasive aspergillosis of the lung with subsequent osteomyelitis of the ribs. Diagnosis was made by puncture of the soft tissues and isolation of Aspergillus fumigatus. Treatment with amphotericin B induced renal function disturbances. It was successfully replaced by AmBisome. Healing occurred with recovery of the immunity of the patient. The literature on Aspergillus osteomyelitis is reviewed.

Adult↗
PubMed1991

Prevalence and type of infertility in Gabon.

The prevalence and type of infertility based on the WHO criteria were determined in a rural and semi-rural population in south-eastern Gabon. The prevalence rate of infertility in the rural population was 5.7% for primary infertility and 20.0% for secondary infertility. In the semi-rural area, 3.0% suffered from primary infertility and 22.4% from secondary infertility. Pregnancy wastage and home delivery were risk factors for secondary infertility. An evaluation of the WHO criteria for fertility surveys was made.

Abortion, Spontaneous↗
PubMed1991

Seroprevalence of retroviral infection in women with different fertility statuses in Gabon, western equatorial Africa.

Seroprevalence of retroviral infection (HIV-1, HTLV-1) in women with different fertility statuses was studied in Gabon (Western Equatorial Africa). The overall prevalence rate of HIV-1 was 1.4% and of HTLV-1, 6.8%. In the primary infertile women the age-adjusted prevalence rate of HIV-1 was significantly higher than in the fertile women (9.3% versus 0.7%) and in secondary infertile women (9.3% versus 2.1%). There was no difference in sero-prevalence of HTLV-1 among women with different fertility statuses, but a steady increase with age was seen. Concomitant infection with HTLV-1 and HIV-1 was observed in two women. In Gabon primary infertile women could be considered a risk group for HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Interleukin-2 reverses T cell unresponsiveness to Plasmodium falciparum-antigen in malaria immune subjects.

Peripheral blood mononuclear cells (PBMC) from a large proportion of 34 healthy adult native residents in a malaria endemic area showed null or marginal proliferative response (low-responders) to schizont-enriched Plasmodium falciparum malaria antigen (M.Ag) but good response to pokeweed mitogen. In contrast, substantial proliferative response to M.Ag was observed in 8/8 adult temporary residents with a history of one to three acute malaria episodes. Purified CD4+ T cells preferentially responded to M.Ag, however in low-responders CD4+ T cell proliferation was poor. Moreover, no inhibition of CD4+ T cell proliferation was observed when graded numbers of CD8+ T cells were added in culture. The addition of recombinant interleukin 2 (rIL-2) to M.Ag restored the proliferative response of low-responders' PBMC. This response was M.Ag-specific when CD4+ T cells grown in M.Ag plus rIL-2, but not in rIL-2 alone, were tested in secondary cultures.

Animals↗
PubMed1990

Defective in vitro production of anti-Plasmodium falciparum antibodies in some malaria-immune subjects.

The cell requirements for immunoglobulin (Ig) and Plasmodium falciparum-specific antibody production in the presence of schizont-enriched malaria antigen (M.Ag) were studied in vitro. Cell donors were healthy immune adult Africans and Europeans who had experienced single P. falciparum acute infection. In the presence of M.Ag a dose-dependent increase in polyclonal IgM and IgG levels was observed with T/B cell cultures from 4/4 European and from 4/14 African donors (high-Ig producers). In 10/14 Africans M.Ag failed to induce significant Ig production (low-Ig producers). No differences in Ig levels between high- and low-Ig producers were observed in the presence of pokeweed mitogen (PWM). The addition of CD8+T cells to CD4+T/B cell cultures significantly suppressed the Ig production in PWM- but not in M.Ag-activated cultures. High levels of P. falciparum-specific antibodies were found in M.Ag-activated cultures from high-Ig producer Africans but not in cultures from Europeans or from low-Ig producer Africans. The in vitro production reflected differences in plasma levels of specific antibodies.

Adolescent↗
PubMed1990

T lymphocyte interferon-gamma production induced by Plasmodium falciparum antigen is high in recently infected non-immune and low in immune subjects.

Interferon (IFN) alpha and gamma were measured by radio-immunoassays in supernatants from cultures of peripheral blood mononuclear cells (PBMC) or purified T cell subsets incubated with either Plasmodium falciparum schizont-enriched malaria antigen (mAg), uninfected red blood cells (RBC) or pokeweed mitogen (PWM). Cell donors were 24 clinically immune, healthy African adult native residents of a P. falciparum-endemic region, Haut-Ogooué, Gabon, and seven non-immune, European temporary residents with a history of a single to a few malaria infections during the previous 1 to 9 months. When PBMC were cultured in medium alone or with RBC antigen no or low titres of IFN-gamma were detected. PBMC proliferation and IFN-gamma production observed in the presence of mAg were dose dependent and significantly correlated. When cultured with mAg, PBMC from non-immune Europeans produced significantly higher levels of IFN-gamma than did PBMC from clinically immune Africans. No such difference was found when PBMC were cultured with PWM. The mAg-induced IFN-gamma production was due mainly to CD4+ T cells and was not enhanced by CD8+ T cell depletion. No IFN-alpha was detected in culture supernatants. Thus, P. falciparum antigens are able to induce in vitro production of IFN-gamma by CD4+ T cells; however, in this sample, individuals considered to be clinically resistant to malaria were low producers of IFN-gamma.

Animals↗
PubMed1989

Interpretation of antibodies reacting solely with human retroviral core proteins in western equatorial Africa.

Out of 4176 sera from asymptomatic adults originating from Chad, equatorial Guinea and Gabon tested for HIV-1 antibodies, 146 (3.5%) were positive by an enzyme immunoassay (EIA). By Western blot (WB), 20 (0.5%) were positive, i.e. with antibodies to the core and the envelope proteins, 96 (2.3%) were indeterminate, i.e. with antibodies to the viral core proteins only and 30 (0.7%) were negative. On testing for HIV-2 by WB, two of the 96 indeterminate sera had antibodies to the HIV-2 envelope glycoproteins. Two complementary tests were used: a radioimmunoprecipitation assay (RIPA) and a HIV EIA recombinant assay (ENVACOR) to check 53 of these indeterminate sera. Forty-one were positive for the p25 protein in RIPA, of which 34 were negative in ENVACOR; six were positive for core proteins only and one was positive for envelope and core proteins using this assay. Twelve of the 53 indeterminate sera were negative in RIPA, of which 11 were negative and one positive for core proteins in ENVACOR. Thus, 42 of these sera remained indeterminate even after the two additional tests which did not allow a distinction between retroviral infection or non-specific reactions. We were able to isolate an unusual HIV-1 virus from lymphocyte cultures of two subjects presenting antibodies directed only against the core proteins.

Africa, Western↗
PubMed1989

Transmission of syphilis between sexual partners in Gabon.

The prevalence and transmission of syphilis was studied in a semirural community in south eastern Gabon. The overall prevalence was 8% (99/1251) and there was no difference in age adjusted prevalence between men and women. The transmission of syphilis between sexual partners occurred in 18.1% (8/44).

Adolescent↗
PubMed1989

Seroepidemiological survey of HTLV-I infection among randomized populations of western central African countries.

Between 1987 and 1988, a survey to determine the distribution of HTLV-I infection was conducted in a representative population of adults, living in southern Chad, Cameroon, and Equatorial Guinea. Populations studied were selected by the cluster sampling technique. Sera were tested for IgG antibodies to HTLV-I by ELISA. ELISA-positive sera were retested by Western blot. The study comprised 2,301 adults, all apparently healthy. Crude prevalence rates range from 0.5 to 11.8%. We found three clearly different areas of HTLV-I seroprevalence rates. An area of low seropositivity in southern Chad and northern Cameroon (0.5-2.0%), an area of moderate seropositivity in the savannah region of Ngaoundere, Cameroon (4.2%) and in Bata, Equatorial Guinea (6.5%), and lastly an area of high seropositivity (8.6-11.8%) in the equatorial forest area of Equatorial Guinea and southern Cameroon. HTLV-I seroprevalence rates increased with age up to 12.6% after 40 years old in the areas of high seropositivity. There was no difference between male and female age-adjusted prevalence rates in all of the areas studied.

Adolescent↗
PubMed1989

Hepatitis B and delta infection in Gabon: a seriological survey in a representative sample of the province of Haut-Ogooue.

Hepatitis B virus markers and antibodies to delta agent were studied in adult people (15-54 years) in the province of Haut-Ogooue (Gabon), randomly selected by cluster sampling technique. Of the 384 people, 37 (9.6%) were positive for HBsAg, of which 23 (62.2%) were positive for HBeAg; 246 (65.3%) had anti-HBs and 53 (13.8%) had anti-HBc as the only marker. Chronic carriage of HBV defined as presence of HBsAg or exclusive anti-HBc was observed in 90 people (32%). At least one of the HBV markers was found in 89% of the people. Women were more frequently positive than men. No difference in relation to age was observed. Anti-delta was found in 12 (3.5%) of the 341 people with HBV markers and 7/12 of these could be considered as chronic HBV carriers.

Adolescent↗