M. Koster

Janssen (Belgium)

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P.J.J. Sauer

Erasmus MC - Sophia Children’s Hospital

R. Woestenborghs

Janssen (Belgium)

E. Chwetzoff

Janssen (France)

C. Malaspina

University of Rome Tor Vergata

J.P. Kistermann

Centre Hospitalier Universitaire Dijon Bourgogne

Anna Maria Tortorano

University of Milan

Aki Ito

Yokosuka Kyosai Hospital

K.P. Hellreigel

Malteser-Krankenhaus

J.S. Hostetler

California Institute for Medical Research

M.A. Viviani

University of Milan

Cooperative Institutions

Janssen (Belgium)

Radboud University Nijmegen

Erasmus MC - Sophia Children’s Hospital

Centre Hospitalier Universitaire Dijon Bourgogne

Erasmus University Rotterdam

Erasmus MC

Radboud University Medical Center

University Medical Center

Maastricht University Medical Centre

George Washington University

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Chemotherapy (1992)

David W. Denning J. Van Cutsem J.S. Hostetler David W. Denning D. A. Stevens

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10.1159/000239085

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116 NEW ANTIFUNGAL DRUGS IN TEH PRETERM NEONATE: PHARMACOKINETICS OF KETNAZOLE AND ITRACONAZOLE

Pediatric Research (1991)

John N. van den Anker M. Koster J Heijkants Pieter J.J. Sauer

10.1203/00006450-199112000-00146

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Riassunti

Chemotherapy (1992)

David W. Denning J. Van Cutsem J.S. Hostetler David W. Denning D. A. Stevens

10.1159/000239081

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[Consequences of diethylstilbestrol during pregnancy; 50 years later still a significant problem].

PubMed (2001)

P.E. Treffers Antonius G.J.M. Hanselaar Th.J.M. Helmerhorst M. Koster F.E. van Leeuwen

Since the 1940s, diethylstilbestrol (DES) has been administered to about three million pregnant women in the United States and in the Netherlands, between 1947 and 1975, to about 220,000. The most important consequences described are: for DES mothers an increased risk of mammary carcinomas and for DES daughters a 1 in 1000 chance of clear cell adenocarcinoma (CCAC) as well as an increased risk of (pre)malignant abnormalities of the stratified epithelium in the vagina and cervix. In addition to this, DES daughters frequently have developmental disorders of the cervix and corpus uteri. In connection with this fertilisation disorders have been described as well as unfavourable outcomes of pregnancy: more ectopic pregnancies, abortion and premature birth. DES sons exhibit an increased frequency of several benign abnormalities of the genitalia. The DES problem continues to be an important issue. The entire cohort of DES mothers is in the age group with a high risk of mammary carcinoma. The youngest DES daughters will be of childbearing age for at least another 15 years; the risk of ectopic pregnancies and pre-term labour is increased. The oldest DES daughters are now reaching postmenopausal age. The incidence of CCAC of the vagina and cervix in the population is bimodal, with a second peak at older age. It is still unknown if at this age DES daughters will have an increased incidence of these malignancies. From animal experiments it becomes clear that DES administration to pregnant mice results in an increased incidence of genital tumours not only in the second generation but also in the third. This has yet to be investigated in humans and deserves special attention. The legally imposed destruction of patient files after a period of ten years is a serious threat to patient care and scientific investigation, notably in obstetrics and child medicine.

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The Treatment of Aspergillosis and Aspergilloma with Itraconazole, Clinical Results of an Open International Study (1982 ‐ 1987)/Die Behandlung der Aspergillose und des Aspergilloms mit Itraconazol, Klinische Ergebnisse einer offenen internationalen Studie (1982 ‐ 1987)

Mycoses (1988)

K. De Beule Piet De Doncker G. Cauwenbergh M. Koster R. Legendre

Summary: A total of 137 patients with aspergillosis or aspergilloma has been treated with 50 to 400 mg itraconazole daily during 11 to 780 days. The global assessments »markedly improved« and »cured« were given to 60% of the treatments in invasive aspergillosis (n = 35) and reached 66% in chronic necrotising pulmonary aspergillosis (n = 44). These response rates are sufficiently high regarding the limited number of antifungal agents useful in aspergillosis. Sixty‐two percent of the chronic pulmonary aspergilloma cases (n = 42) showed symptomatic improvement and the radiological picture had improved in 30%. In one patient, the fungus ball disappeared during long‐term treatment. The results in five allergic bronchopulmonary aspergillosis (ABPA) patients indicate a possible role for itraconazole as complementary treatment to corticosteroids. All seven patients with cutaneous aspergillosis were mycologically and clinically cured after a maximum of 158 days of treatment. Two out of three biopsy proven cases of bone aspergillosis responded to itraconazole therapy. These long‐term treatments with itraconazole were well tolerated. The reported side effects were merely of gastro‐intestinal origin and there was no effect on the most important biochemical and haematological parameters. Itraconazole appears to be a valuable new tool in the treatment of aspergillosis. Zusammenfassung: Eine Gesamtzahl von 137 Aspergillose‐ und Aspergillom‐Patienten wurde mit 50–400 mg Itraconazol täglich über Perioden zwischen 11 und 780 Tagen behandelt. Das Globalurteil »wesentlich gebessert« oder »geheilt« erhielten 60% der Behandelten mit invasiver Aspergillose (n = 35) und 66% der Patienten mit chronisch nekrotisierender Lungenaspergillose (n = 44). Diese Ansprechquoten sind recht hoch, wenn man die beschränkte Anzahl der bei Aspergillose wirksamen Antimykotika berücksichtigt. Bei 62% der Fälle mit chronischem Lungenaspergillom (n = 42) wurde eine symptomatische Besserung erzielt, bei 30% besserte sich das radiologische Bild. Bei einem Patienten verschwand der Fungusball während Langzeitbehandlung. Die Ergebnisse von 5 Patienten mit allergischer bronchopulmonaler Aspergilose (ABPA) deuten auf die mögliche Rolle von Itraconazol bei einer Kombinationsbehandlung mit Kortikosteroiden. Alle 7 Patienten mit kutaner Aspergillose waren nach einer maximalen Behandlungsdauer von 158 Tagen mykologisch und klinisch geheilt. Zwei von 3 bioptisch nachgewiesenen Fällen mit Knochenaspergillose sprachen auf Itraconazol‐Behandlung an. Die Langzeitbehandlung mit Itraconazol war gut verträglich. Die angegebenen Nebenwirkungen waren meist gastrointestinalen Ursprunges, die wesentlichsten biochemischen und hämatologischen Parameter blieben unbeeinflußt. Damit erweist sich Itraconazol als ein wertvolles neues Medikament bei der Behandlung der Aspergillose.

Aspergilloma

Allergic bronchopulmonary aspergillosis

10.1111/j.1439-0507.1988.tb03653.x

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Citations (155)

Contents, Vol. 38, Supplement 1, 1992

Chemotherapy (1992)

David W. Denning J. Van Cutsem J.S. Hostetler David W. Denning D. A. Stevens

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10.1159/000239047

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Efficacy of Itraconazole in the Prevention of Fungal Infections Among Neutropenic Patients with Hematologic Malignancies and Intensive Chemotherapy. A Double Blind, Placebo Controlled Study

Leukemia & lymphoma/Leukemia and lymphoma (1993)

Gerard Vreugdenhil Beatrix J. Van Dijke J. Peter Donnelly I.R.O. Nováková John Raemaekers

We studied the efficacy and safety of itraconazole for the prevention of fungal infection in neutropenic patients given cytotoxic chemotherapy for hematologic malignancies. Patients were randomly allocated to receive either itraconazole (200 mg bd) or placebo in addition to oral amphotericin B until the patient either developed fungal infection or had completed antileukemic treatment. Forty six patients (83 neutropenic episodes) treated with itraconazole and 46 placebo treated patients (84 neutropenic episodes) were evaluable. No specific toxicity was noted. Nine fungal infections developed in the itraconazole group, of which four were histologically or microbiologically proven and 15 in the patients given placebo (eight proven) (p < 0.12). All these patients received IV amphotericin B. The incidence of Candida albicans infections tended to be lower in the itraconazole group, but overall, there was no measurable improvement in the prevention of fungal infections and mortality by itraconazole.

10.3109/10428199309067926

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Itraconazole Serum Levels in the Preterm Neonate

Chemotherapy (1992)

John N. van den Anker M. Koster R. Woestenborghs P.J.J. Sauer

The increasing use of invasive procedures and antibiotic treatments has caused an increase in candidal infections in preterm neonates. Antifungal drugs currently used are toxic (amphotericin B) or lead to rapid development of resistant Candida strains (flucytosine). This has led to a search for new, less toxic, drugs. The bioavailability of itraconazole, an oral antifungal agent with broad-spectrum activity and low toxicity, was therefore investigated. Trough and peak serum levels of itraconazole were measured by high performance liquid chromatography in 6 preterm neonates (gestational age, 25.6 ± 0.8 weeks; weight, 760 ± 120 g), 48 h after initiating therapy with itraconazole, 5 mg/kg/day, in hydroxypropyl-Β-cyclodextrin solution. The area under the curve could be determined in 4 neonates (gestational age, 25.7 ± 1.0 weeks; weight, 825 ± 55 g) with a dose interval of 24 h. The parameters obtained were: trough, 85 + 18 ng/ml; peak, 276 ± 41 ng/ml; AUC (0-24 h), 5,138 ± 1,188 ng·h/ml. It was concluded that itraconazole, 5 mg/kg/day, is well absorbed and recommended levels are reached in preterm neonates of less than 32 weeks gestational age. No side-effects were seen. Itraconazole may be a useful antifungal drug in preterm neonates, but further studies on efficacy and safety are needed.

10.1159/000239078

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Itraconazole versus griseofulvin. A double-blind comparison in patients with tinea corporis and tinea cruris

Journal of Dermatological Treatment (1992)

A. Notowicz M. Koster

The efficacy of two oral antifungal drugs, itraconazole and griseofulvin, in tinea corporis and tinea cruris was compared in a doubleblind trial. Patients were treated with itraconazole (n = 15, 100mg/day) or griseofulvin (n = 14, 500mg/day) for 2 weeks. The clinical outcome was in favour of itraconazole. After 2 weeks 60% of the patients treated with itraconazole were cured, and 21% of those treated with griseofulvin. Equivalent figures 2 weeks after the end of the treatment, were 67% and 29%, respectively. Both treatments were well tolerated.

Griseofulvin

Tinea Capitis

Dermatophyte

10.3109/09546639209092755

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Citations (3)

Author Index

Chemotherapy (1992)

David W. Denning J. Van Cutsem J.S. Hostetler David W. Denning D. A. Stevens

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10.1159/000239083

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