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J J Heimans

Publications and source records attributed to J J Heimans.

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

Paclitaxel-induced neuropathy.

BACKGROUND: Paclitaxel (Taxol) is a new antineoplastic agent derived from the bark of the western yew, Taxus brevifolia, with important activity against several tumors such as ovarian cancer, breast cancer, lung cancer and head and neck cancer. Because it promotes microtubule assembly, neuropathy occurs as one of its toxic side effects. Our purpose was to evaluate the incidence, severity, dose-dependency and reversibility of paclitaxel-induced neuropathy. PATIENTS AND METHODS: We prospectively studied 27 patients treated with single-agent paclitaxel at three dose levels. Paclitaxel was administered by 3-hour intravenous infusion every three weeks in all patients, and if possible, all were evaluated neurologically before paclitaxel, after every other cycle and after discontinuation of therapy. We used a standardized questionnaire and neurologic examination with emphasis on neuropathic symptoms and signs. The severity of symptoms and signs was scored. Quantitatively, vibratory perception threshold (vibrameter) and grip strength (dynamometer) were measured. RESULTS: Six, 14 and seven patients were treated with 135 mg/m2, 175 mg/m2 and 250-300 mg/m2, respectively. Neuropathic symptoms occurred in 50%, 79% and 100%, neuropathic signs in 83%, 86% and 100%, and dose-limiting neurotoxicity in 0%, 21% and 71% of patients, respectively. Neurotoxicity progressed with higher cumulative dose and was more pronounced with higher dose per course. Paclitaxel-induced neuropathy was predominantly sensory in character, though minor motor signs were present. Follow-up data of 12 patients after discontinuation of paclitaxel therapy showed that paclitaxel-induced neuropathy is at least partially reversible. CONCLUSIONS: Paclitaxel-induced neuropathy is a dose-dependent phenomenon, occurring with higher cumulative dose and higher dose per cycle. Using 3-weekly 3-hour infusions of paclitaxel, dose-limiting neurotoxicity can be expected in patients treated with 250 mg/m2 or more each cycle.

Adult↗
PubMed1995

High-dose paclitaxel with granulocyte colony-stimulating factor in patients with advanced breast cancer refractory to anthracycline therapy: a European Cancer Center trial.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is a novel cytostatic agent that has shown interesting antitumor activity in patients with advanced breast cancer. Depending on variable patient characteristics and amount and type of prior therapy, as well as the applied dose and schedule of paclitaxel, response rates have varied from 13% to 62%. However, optimal dose and schedule are still unknown. We studied a high-dose (250 to 300 mg/m2) 3-hour paclitaxel infusion schedule in a poor prognostic group of breast cancer patients who progressed or relapsed while taking anthracyclines. This regimen was given every 3 weeks. Twenty-one of the 36 patients studied had increased liver enzymes and 18 had documented liver metastases. The objective response rate was only 6%, but response rate by disease site indicated that soft tissue lesions responded in 30% of cases. For a better comparison with other reported data a uniform definition of "anthracycline refractory" is needed. Neuropathy, which was found to be dose limiting, and arthralgia/myalgia syndrome were the most frequently occurring toxicities. Both severe myelosuppression (and infections) and severe diarrhea and mucositis were reported more frequently in patients with liver dysfunction. As higher peak levels, increased areas under the concentration time curves, and longer times during which plasma concentrations were above the threshold level of 0.1 mumol/L were found in patients with elevated liver enzymes, a correlation with the observed toxicities is assumed. Further pharmacodynamic studies in such patients receiving a 3-hour infusion seem warranted.

Adult↗
PubMed1994

[2 patients with paraplegia caused by spinal cord tumor metastases].

In two women, 72 and 65 years old, medullary metastases were found of a mammary adenocarcinoma and a small cell bronchial carcinoma respectively. Radiotherapy and corticosteroids led to stabilisation and functional recovery, but the patients died shortly afterwards. Intramedullary spinal cord metastasis is an infrequent but devastating complication of cancer. The treatment options are limited and the prognosis is poor.

Adenocarcinoma↗
PubMed1994

Cognitive functions and quality of life in patients with low-grade gliomas: the impact of radiotherapy.

The role of early radiotherapy in the treatment of low-grade gliomas is controversial. For this reason the impact of radiotherapy on quality of life was studied in long-term survivors of biopsy-proved low-grade gliomas without signs of tumor recurrence. Twenty patients (age range, 18-66 years) had been treated with early radiotherapy; the other 21 patients (age range, 19-65 years) had undergone surgery or biopsy only. The interval from diagnosis to testing ranged from 1 to 12 years (mean, 3.5 years). Nineteen patients with low-grade hematological malignancies, surviving 1 to 15 years without central nervous system involvement, served as control subjects. Apart from the neurological and functional status, the patients' cognitive, affective, and psychological status was determined. None of the survivors had significant neurological impairment and the Karnofsky index for them was at least 70. However, more specific examinations of cognitive functions and the affective status (Profile of Mood States) indicated that, compared to the control subjects, the patients with low-grade gliomas had significantly more cognitive disturbances and suffered more frequently from fatigue and depressed moods. The two groups with low-grade gliomas, on the other hand, did not differ significantly on any of these measures. It is concluded that radiotherapy did not cause these disturbances and had no negative impact on quality of life in these patients.

Adolescent↗
PubMed1994

Radiotherapy response of cerebral metastases quantified by serial MR imaging.

A patient with cerebral metastases, treated with radiotherapy, underwent serial gadolinium-enhanced MR imaging. The MR images were quantified using home developed software to evaluate the changes in volumes of tumor mass and edema after radiotherapy (mean precision of the quantification technique less than 5%). The decrease in tumor volume and edema observed after radiotherapy preceded clinical improvement. The presented technique can be used to accurately assess, more directly than using clinical scales, the effect of putative therapies.

Brain Edema↗
PubMed1994

Effects of the ACTH(4-9) analogue, ORG 2766, on vincristine cytotoxicity in two human lymphoma cell lines, U937 and U715.

The use of cytotoxic drug vincristine (VCR) is limited by the occurrence of peripheral neuropathy. A neurotrophic ACTH(4-9) analogue, ORG 2766, is being studied for its protective effect. Possible modulatory effects of ORG 2766 on tumour cell growth and interference with the cytotoxic efficacy of VCR were studied in two human lymphoma cell lines, U937 and U715. The effects of ORG 2766 on cell growth and survival and on VCR-mediated cytotoxicity were investigated using two MTT-based assays to study direct cytotoxic effects and to assess residual growth after pretreatment. Treatment with ORG 2766 alone had no effect on cell growth and survival. Neither did this drug affect VCR cytotoxicity. However, after 96 h pretreatment with ORG 2766 and a culture period of 7 days, a reduction in residual growth and a potentiation of VCR-induced inhibition of growth capacity was observed in U715 cells, and to some extent also in U937 cells. It is concluded that ORG 2766 has no stimulatory effects on tumour growth and does not negatively interfere with VCR-mediated cytotoxicity. Rather it enhances the cytostatic effect of VCR. It is suggested that ORG 2766 can safely be used in clinical trials investigating the ability of ORG 2766 to counteract VCR-induced neurotoxicity.

Adrenocorticotropic Hormone↗
PubMed1994

Paclitaxel (Taxol) concentrations in brain tumor tissue.

BACKGROUND: Paclitaxel (Taxol) is a novel chemotherapeutic agent, active against a variety of tumors. It is not known whether the drug penetrates brain tumor tissue. PATIENTS AND METHODS: Three patients with a recurrent glioma received paclitaxel (175 mg/m2) in a 3-hour i.v. infusion prior to surgery. Paclitaxel concentrations were measured in the tumor tissue, cerebrospinal fluid, cyst fluid, plasma and, in one patient, normal brain tissue. RESULTS: Tumor tissue concentrations were in the therapeutic range in all three patients. Brain tissue concentration, however, was below the detection limit of the trial. CONCLUSIONS: These findings suggest that paclitaxel may have a place in brain tumor therapy. The low concentration in normal brain tissue, as observed in one patient, may suggest, however, that the drug does not cross the intact bloodbrain barrier.

Adult↗
PubMed1993

[Neurologic consultation in cancer patients].

OBJECTIVE: To inventory neurological complications in patients with cancer. DESIGN: Descriptive study. SETTING: University Hospital Vrije Universiteit, Amsterdam. METHOD: Data were collected from 718 neurological consultations with 610 admitted oncological patients from 1990 to 1992. RESULTS: In 203 cases backache, sometimes radiating to the leg, prompted the request for neurological consultation. In 142 cases a metastasis in the vertebrae could be detected; in 64 cases there were signs and/or symptoms of compression. Cerebral metastasis occurred in 133 patients in which eventuality neurological dysfunctions were the main initial manifestations. In all, 32 cases of leptomeningeal metastasis were diagnosed, mostly associated with carcinoma of the breast or haematological system. In 30 cases there was growth of a primary tumour or metastasis into a plexus or peripheral nerve. Non-metastatic complications consisted of paraneoplastic, iatrogenic and other (mostly metabolic or toxic encephalopathy) causes. A paraneoplastic complication was seen in only 6 cases. Iatrogenic complications were most frequently caused by cytotherapy. CONCLUSION: Numerous neurological complications can occur in patients with cancer. Timely treatment of metastatic complications can prevent serious disablement in a terminal stadium of the disease.

Adolescent↗
PubMed1993

Treatment of diabetic autonomic neuropathy with an aldose reductase inhibitor.

To evaluate the effects of the aldose reductase inhibitor Ponalrestat (Statil) on diabetic autonomic neuropathy, a double-blind placebo controlled trial was carried out on a group of 34 diabetic patients with documented cardiac autonomic neuropathy. After a 4-week, placebo run-in period, patients were randomised for treatment with 600 mg Statil or placebo for another 24 weeks. Moreover, the reliability of the autonomic nerve function tests was investigated by comparing the results at onset and at week 4. Fifteen patients treated with Statil and 12 with placebo completed the study. Neither symptom scores nor cardiovascular reflexes, pupil reflexes and skin vasomotor reflexes improved after Statil therapy, which led us to conclude that Statil is not effective in the treatment of diabetic autonomic neuropathy. Reliability coefficients for cardiovascular reflexes and pupil reflex showed high values, ranging from 60% to 80%. Therefore these methods are recommended in future therapy trials.

Aldehyde Reductase↗
PubMed1993

Methotrexate induced brain necrosis and severe leukoencephalopathy due to disconnection of an Ommaya device.

A 63-year old woman with breast carcinoma developed leucoencephalopathy and local brain necrosis after intraparenchymal infusion of methotrexate. This iatrogenic condition was caused by drain disconnection of the Ommaya device (bore hole type). The diagnosis of this rare complication of an Ommaya device was based on multiplanar MR-imaging. The case is discussed with regard to the complications of intraventricular chemotherapy by means of an Ommaya reservoir.

Brain↗
PubMed1993

Hypophyseal non-Hodgkin's lymphoma presenting with clinical panhypopituitarism successfully treated with chemotherapy.

A patient is described with a testicular Non-Hodgkin's Lymphoma (NHL) presenting with panhypopituitarism caused by a hypophyseal localization. A 67Gallium scintigraphy showed avid uptake in the hypophyseal region. Obviously 67Gallium could reach the tumor, by the intravenous route, which was the reason to treat the patient with intravenous chemotherapy. A complete remission was induced, which seems to be lasting (+25 months). As far as we know this is the first report of panhypopituitarism caused by a hypophyseal NHL in the hypophysis and successfully treated by intravenous chemotherapy.

Aged↗
PubMed1993

Long-term effects of vincristine on the peripheral nervous system.

Forty patients with Non-Hodgkin's Lymphoma treated with vincristine between 1984 and 1990 (cumulative dose 12 mg in 18-24 weeks) were investigated in order to evaluate the long term effects of vincristine on the peripheral nervous system. The patients were interviewed with emphasis on neuropathic symptoms. Physical and quantitative sensory examination with determination of vibratory perception and thermal discrimination thresholds were performed, four to 77 months (median 34 months) after vincristine treatment. Twenty-seven patients reported neuropathic symptoms. In 13 of these 27 patients symptoms were still present at the time of examination. In these patients sensory signs and symptoms predominated. In the other 14 patients symptoms had been present in the past. Symptoms persisted maximally 40 months since cessation of therapy. There was no age difference between patients with and without complaints at the time of examination. Normal reflexes were found in two third of patients. Neuropathic complaints were not very troublesome on the long term. It is concluded that with the above mentioned vincristine dose schedule signs and symptoms of vincristine neuropathy are reversible for a great deal and prognosis is fairly good.

Adult↗
PubMed1993

Angiotropic intravascular large-cell lymphoma with massive cerebral extension.

Angiotropic intravascular large-cell lymphoma (AILL) is a rare, generally fatal disease characterised by a multifocal proliferation of neoplastic mononuclear cells within small blood vessels. The diagnosis of a patient was made at necropsy. The malignant cells had infiltrated the periventricular areas of the brain.

Brain↗
PubMed1992

Growth inhibition of human glioma cells induced by 8-chloroadenosine, an active metabolite of 8-chloro cyclic adenosine 3':5'-monophosphate.

8-Chloroadenosine 3':5'-monophosphate (8ClcAMP) inhibits the growth of human glioma cell lines at much lower concentrations than more commonly used cyclic AMP analogues, without inducing morphological differentiation. The mechanism by which 8ClcAMP exerts this effect is not fully understood. We examined whether the growth-inhibitory effect of this compound is due to an active metabolite, using a sulforhodamine protein stain assay to determine the proliferation rate of the WF human glioma cell line. 8-Chloroadenosine, one of the metabolites, inhibited the proliferation of WF human glioma cells more potently than 8ClcAMP. In the presence of adenosine deaminase, which converts 8-chloroadenosine into 8-chloroinosine, 8-chloroadenosine no longer inhibited human glioma cell growth. Addition of adenosine deaminase also largely reduced the growth-inhibitory effect of 8ClcAMP, but not of 8-(4-chlorophenylthio)cAMP. High performance liquid chromatography analysis revealed that at least part of the 8ClcAMP in the culture medium is converted into 8-chloroadenosine. We concluded that 8ClcAMP exerts its growth-inhibitory effect through its active metabolite 8-chloroadenosine. Adenylate cyclase assays showed that 8-chloroadenosine does not affect the intracellular cAMP production through adenosine A1 or A2 receptor activation, which makes it unlikely that 8-chloroadenosine inhibits glioma cell growth by increasing the intracellular cyclic AMP concentration.

2-Chloroadenosine↗
PubMed1992

A pilot study on the influence of a corticotropin (4-9) analogue on Vinca alkaloid-induced neuropathy.

In a randomized, double-blind, placebo-controlled pilot study, we examined the effect of Org 2766--a corticotropin (4-9) analogue--on neurotoxicity in 28 patients with lymphoma who were treated with combination chemotherapy containing Vinca alkaloids (vincristine and vinblastine). The patients received a total dose of 12 mg of vincristine in the case of non-Hodgkin's lymphoma and a total dose of 16 mg of vincristine in the case of Hodgkin's disease. Moreover, the patients with Hodgkin's disease received a mean total dose of 84 mg of vinblastine. Subcutaneous injections of 2 mg of Org 2766 or placebo were administered to patients with non-Hodgkin's lymphoma on days 1 and 10 of each chemotherapy course and to patients with Hodgkin's disease on days 1 and 8 of each chemotherapy course. The first injection was always given before the administration of vincristine. Assessment of neurologic symptoms and signs and measurement of sensory thresholds (vibration sense and temperature sense) were performed on day 1 of the first, fourth, and sixth (or eighth) courses and 6 weeks after cessation of chemotherapy. Thirteen patients (mean age, 44.7 years) received Org 2766 and 15 patients (mean age, 54.7 years) received placebo. More symptoms occurred in the placebo group, but only numbness and autonomic complaints occurred significantly more often in the placebo group. Motor deficit and sensory disturbances were more severe and also occurred significantly more often in the placebo group. There was no difference with respect to reflex examination findings and sensory thresholds.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1992

Implication of glucocorticoid receptors in the stimulation of human glioma cell proliferation by dexamethasone.

Dexamethasone is frequently used in the therapy of brain tumor patients. We investigated the effect of dexamethasone on the proliferation of three short-term and four established human glioma cell lines in vitro, using a microculture tetrazolium assay to determine growth rates. In one short-term culture and in one established cell line dexamethasone consistently stimulated the proliferation in a concentration-dependent way. The proliferation was maximally enhanced at a concentration of approximately 0.1 microM. In these two cell lines a relatively high level of glucocorticoid receptors was present, whereas low levels of glucocorticoid receptors were found in the other cell lines. In addition, we demonstrated that the stimulatory effects of dexamethasone on the proliferation of the glioma cell lines can be antagonized by the antiglucocorticoid RU38486. The results demonstrate unequivocally that the glucocorticoid receptor plays a role in the growth stimulating effect of dexamethasone.

Cell Division↗
PubMed1992

8-Chloro-cyclic adenosine monophosphate, a novel cyclic AMP analog that inhibits human glioma cell growth in concentrations that do not induce differentiation.

Cyclic AMP is supposed to play a role in cell growth and differentiation via activation of protein kinase A. The cAMP signal transduction pathway may therefore be used as a target for the development of anticancer drugs. We compared the effects of 8ClcAMP, a newly developed cAMP analog, to the effects of more commonly used cAMP analogs on the morphology and the proliferation of three human glioma cell lines. 8ClcAMP was the most potent growth inhibitor, exhibiting an IC50 of approximately 10 microM and inducing growth arrest in all three glioma cell lines at a concentration of 100 microM. The cAMP analogs 8CPTcAMP, dibutyryl cAMP, and 8BrcAMP were much less potent. If used in concentrations that induce growth arrest, both 8CPTcAMP and IBMX, but not 8ClcAMP, induced morphological differentiation of the glioma cells. Apparently, the growth-inhibiting effect of 8ClcAMP is not paralleled by its ability to induce morphological differentiation. The explanation for this phenomenon may be that 8ClcAMP does not exert its growth-inhibiting effect via activation of cAMP-dependent protein kinase. Two alternative mechanisms of action are discussed. Since 100 microM 8ClcAMP retarded the growth of normal rat astrocytes only to a marginal extent, without cytotoxic effects, it is concluded that 8ClcAMP may offer interesting perspectives in the treatment of malignant glioma.

1-Methyl-3-isobutylxanthine↗