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J J Heimans

Publications and source records attributed to J J Heimans.

At least 37 records · Page 2Linked to original sources
PubMed2000

A phase II study of paclitaxel in chemonaïve patients with recurrent high-grade glioma.

BACKGROUND: The prognosis of malignant gliomas remains poor. In recurrent disease, chemotherapy can be considered. PATIENTS AND METHODS: In this phase II study we determined the anti-tumour efficacy of paclitaxel 200 mg/m2 in a three-hour intravenous infusion every three weeks in chemonaïve patients with recurrent high-grade glioma in terms of response, survival, and quality of life. RESULTS: In 17 patients (14 glioblastoma multiforme, 3 anaplastic astrocytoma) 69 paclitaxel cycles were administered. Partial or complete responses were not observed. Stable disease for four to six months was observed in five patients (29%). Median time to progression and median survival were two and 10 months, respectively. Toxicity due to paclitaxel was as to be expected and minor in most cases. Quality of life and mood estimates appeared rather stable over time. CONCLUSIONS: We conclude that three-weekly 200 mg/m2 paclitaxel chemotherapy for patients with recurrent high-grade gliomas did not lead to major complications or adverse effects on quality of life and mood. However, this therapy is of only very limited value in terms of response and survival in such patients.

Adult↗
PubMed1999

In vitro protection from cisplatin-induced neurotoxicity by amifostine and its metabolite WR1065.

Cisplatin-induced neuropathy is a major dose-limiting toxicity. Counteraction by amifostine and its metabolite WR1065 may reduce peripheral neurotoxicity in a number of patients. Using the nerve growth factor (NGF)-dependent neurite outgrowth from the PC12 pheochromocytoma cell line as an in vitro assay for neurotoxicity, the protective effects of amifostine and WR1065 against cisplatin action on neurite formation by PC12 cells were studied. Cisplatin in a concentration of 10 microg/ml significantly decreased the percentage of neurite forming cells from 84% to 40%. Amifostine in doses of 0.4 and 0.8 mM proved to protect significantly against the cisplatin-induced decrease in neurite formation, when co-incubated with cisplatin. Also the metabolite WR1065 protected significantly against cisplatin neurotoxicity in a dose of 0.12 mM. Our results show a significant protection by amifostine and its main metabolite WR1065 against cisplatin-induced neurotoxicity using an in vitro model.

Amifostine↗
PubMed1999

Peripheral neuropathy due to biweekly paclitaxel, epirubicin and cisplatin in patients with advanced ovarian cancer.

We assessed the peripheral neuropathic changes induced by biweekly combination chemotherapy including paclitaxel 100-165 mg/m2 (in a 3-h infusion), epirubicin 75 mg/m2 and cisplatin 50 mg/m2 (TEC) in patients with advanced ovarian cancer. Neurologic evaluation, including a standardized questionnaire, bed-side neurological examination, and quantitative determination of vibratory perception thresholds (VPT) and grip strength took place before therapy, after 3 and 6 cycles, and thereafter whenever possible. During chemotherapy all patients received granulocyte colony-stimulating factor from days 2 to 12. Pretreated patients received amifostine two times, before epirubicin and before cisplatin administration. Neuropathic symptoms developed in 11/13 non-pretreated patients and in 7/9 chemotherapy-pretreated patients. Neuropathic signs developed in all patients. Neuropathic symptoms and signs were predominantly sensory in character. VPT changes developed primarily in the feet. According to National Cancer Institute of Canada Common Toxicity Criteria, grade 3 peripheral neuropathy after 6 cycles developed in 1/6 and 2/4 non-pretreated patients who received TEC containing paclitaxel 150 and 165 mg/m2, respectively. We conclude that peripheral neuropathy is dose-limiting in chemonaïve patients treated with biweekly TEC combination chemotherapy, at paclitaxel dose level 165 mg/m2 in a 3-h intravenous administration.

Adult↗
PubMed1999

Comparative double blind clinical trial of phenytoin and sodium valproate as anticonvulsant prophylaxis after craniotomy: efficacy, tolerability, and cognitive effects.

OBJECTIVE: To determine the efficacy, tolerability, and impact on quality of life and cognitive functioning of anticonvulsant prophylaxis with phenytoin or sodium valproate in patients after craniotomy. METHODS: A prospective, stratified, randomised, double blind single centre clinical trial was performed, comparing two groups of 50 patients each, who underwent craniotomy for different pathological conditions and who were treated for 1 year after surgery with either 300 mg phenytoin/day or 1500 mg sodium valproate/day. During the study period patients were seen in the outpatient clinic at 1.5, 3, 6, and 12 months, when medical history, adverse events, and drug plasma concentrations were evaluated. Neuropsychological functioning and quality of life were assessed on the last three visits. In cases of a seizure an EEG was performed, drug plasma concentration assessed, and medication subsequently increased. RESULTS: Of the 100 included patients 14 (seven in each group) experienced one or more postoperative seizures. Severity of the seizures was comparable in the two groups. In all patients, drug plasma concentrations were in the low or subtherapeutic ranges at the time of the first postoperative seizure. Five patients in the phenytoin group and two in the valproate group had to stop their treatment due to drug related adverse events. Sixty patients completed the 12 month period. Analysis of neuropsychological and quality of life data showed no significant differences. CONCLUSION: For efficacy, tolerability, impact on cognitive functioning, and quality of life, no major differences were found between phenytoin and valproate prophylaxis. Valproate is an alternative for anticonvulsant prophylaxis in patients after craniotomy.

Adult↗
PubMed1998

Ten patients with refractory status epilepticus in an intensive care department.

Status epilepticus (SE) is a serious disease, associated with a high morbidity and mortality, particularly if refractory to initial therapy. We describe the clinical manifestations and outcome in ten cases with refractory SE admitted to our medical intensive care unit. Three of these selected group of cases with SE had pre-existent epilepsia. Of the seven patients with new-onset epilepsia, six had multiple underlying systemic diseases. The three patients with pre-existent epilepsia had a favourable outcome of their SE. However, in the seven patients without known structural and/or functional cerebral defects SE was also refractory to second or third line therapy. Administration of thiopental suppressed epileptic activity only temporarily. None of them survived due to coexistent pathology and the onset of secondary metabolic complications. Thus, especially cases with new-onset epilepsia debuting as refractory SE in the presence of underlying systemic diseases had a fatal outcome in our medical intensive care unit.

Adult↗
PubMed1998

Vinca-alkaloid neurotoxicity measured using an in vitro model.

Neurotoxicity forms a major limitation in many clinical applications of vincristine and other powerful vinca alkaloid anticancer drugs. Using the nerve growth factor (NGF) dependent neurite outgrowth from the PC12 pheochromocytoma cell line as an in vitro assay for neurotoxicity, the effect of different concentrations of vincristine (0.55; 1.1 and 11 nM) was compared with that of vindesine and vinblastine. Vincristine in comparatively low concentration (0.55 nM) could significantly decrease the percentage of neurite forming cells from 74% to 32% within a three day incubation period. Especially the longer neurites (> 2 x cell body) proved to be extremely sensitive for vincristine effects. Vinblastine and vindesine were also able to decrease, dose dependently and significantly, the percentage of neurite forming cells. However, the effects observed were less severe than that of vincristine. The sequentially increasing level of neurotoxicity due to vinblastine, vindesine and vincristine, as observed in the neurite outgrowth inhibition correlates well with previous findings from animal models and with data from the clinical practice. Withdrawal of vincristine resulted in a rapid restoration of neurite formation, suggesting the potential reversibility of neurotoxic effects in these cells. These results provide a validation of the PC12 neurite outgrowth assay as a suitable and reliable model for predicting neurotoxicity.

Animals↗
PubMed1998

Neurotoxicity of combination chemotherapy with procarbazine, CCNU and vincristine (PCV) for recurrent glioma.

In cerebral glioma combination chemotherapy with procabazine, CCNU and vincristine (PCV) is used as adjuvant therapy in cases of recurrence. Standard PCV is usually well tolerated, but intensive PCV (CCNU 130 mg/m2 on day 1, procarbazine 75 mg/m2 on day 8-21, vincristine 1.4 mg/m2 on day 8 and 29; 6 courses every 6 weeks) is less well tolerated. We observed central neurotoxic side effects (focal neurological deficit, cognitive disturbances, slowing of EEG background activity, atrophy on cerebral MR) in combination with hematological and hepatic toxicity in four of 26 PCV treated patients with recurrent glioma. Prolonged myelo-suppression and/or ongoing (partial reversible in two patients) neurological deficit still influence daily life in three of four patients months after discontinuation of chemotherapy. Despite the fact that all four patients used anticonvulsants and have been treated with radiotherapy in the past, we have the strong impression that central neurotoxic side effects are related to intensive PCV therapy. We advocate to use the standard PCV regimen in patients with recurrent glioma, because of this potential toxicity and the lack of evidence that intensive PCV leads to better tumor control than standard PCV in cerebral glioma.

Adult↗
PubMed1998

Thallium-201 SPECT as response parameter for PCV chemotherapy in recurrent glioma.

Combination chemotherapy with procarbazine, CCNU and vincristine (PCV) may be effective in patients with recurrent glioma. Response monitoring is mandatory, but radiological response evaluation is often difficult. We evaluated Thallium-201 (201Tl) SPECT as a response parameter in ten patients treated with intensive PCV chemotherapy for recurrent glioma. 201Tl-SPECT studies showed early changes (decreasing volume and intensity) in nine patients and these changes were more pronounced than radiological findings. 201Tl-SPECT results after completion of chemotherapy seemed to correlate with clininal findings during follow up. We conclude that 201Tl-SPECT may contribute to the assessment of response in patients treated with PCV chemotherapy for recurrent glioma.

Adult↗
PubMed1998

Pitfalls in grading severity of chemotherapy-induced peripheral neuropathy.

BACKGROUND: Reliable reporting of chemotherapy-induced neurotoxicity is important. The objectives of the current study were to evaluate the differences in the peripheral neurotoxicity sections of several widely used chemotherapy-related toxicity grading systems, and the differences in the way in which observers interpret these scales. PATIENTS AND METHODS: Two neurologists independently rated the severity of chemotherapy-induced peripheral neuropathy, according to WHO, ECOG, Ajani, and NCIC-CTC criteria in 37 patients. RESULTS: The highest percentage grade 1, grade 2 and grade 3 peripheral neurotoxicity was noted when employing the WHO, Ajani and NCIC-CTC scales, respectively. Percentage inter-observer agreement across all grades of severity ranged from 45.9 (NCIC-CTC) to 83.8 (WHO). The degree of agreement varied from 'poor to fair' to 'substantial'. Percentage inter-observer agreement for the dichotomy grade < or = 2 and grade 3 ranged from 81.1 (NCIC-CTC) to 94.6 (Ajani and WHO), however, exact agreement on grade 3 peripheral neurotoxicity ranged from 0 (Ajani and WHO) to 42% (NCIC-CTC). Percentage interscale agreement for the dichotomy grade < or = 2 and grade 3 varied from 67.6 (WHO and NCIC-CTC) to 100 (WHO and ECOG). Interobserver disagreement of severity grading was partly due to different interpretation of scale parameters. CONCLUSIONS: Our results suggest that caution should be used in interpreting results across studies using different scales for neurotoxicity grading in chemotherapy-related peripheral neuropathy. When (multicentre) trials are to be undertaken with potential neurotoxic or neuroprotective agents, consensus should be sought regarding the toxicity rating scale used, and its interpretation by participating physicians.

Adult↗
PubMed1998

Response rate and prognostic factors of recurrent oligodendroglioma treated with procarbazine, CCNU, and vincristine chemotherapy. Dutch Neuro-oncology Group.

OBJECTIVES: To determine the response rate and factors correlated with response of oligodendroglial tumors to procarbazine, lomustine (CCNU), and vincristine (PCV) chemotherapy. DESIGN: Retrospective, observational multicenter study. METHODS: Patients treated with PCV or intensified PCV chemotherapy for a recurrent oligodendroglial tumor after surgery and radiation therapy with measurable disease were retrospectively evaluated for response. A 50% reduction in cross-sectional enhancing tumor area was considered a partial response. Stabilized or responding patients received six cycles of PCV unless unacceptable toxicity occurred. RESULTS: Fifty-two patients were included; median time to progression (MTP) for the entire group was 10 months. In 17% of patients a complete response (MTP, 25 months) was obtained, and in 46% a partial response (MTP, 12 months) was obtained. Median overall survival was 20 months. Although treatment was discontinued for toxicity in seven patients, it was generally well tolerated. The intensified PCV regimen was more toxic. Patients initially presenting with seizures and patients with tumor necrosis in histologic specimens had a better response rate in contrast to patients who had their first relapse within 1 year of first treatment (surgery and radiation therapy). CONCLUSIONS: Oligodendroglial tumors are chemosensitive, but most patients will have relapsed after 12 to 16 months. New studies must aim at improving initial treatment and second-line chemotherapy.

Adolescent↗
PubMed1997

The antiproliferative effect of 8-chloro-adenosine, an active metabolite of 8-chloro-cyclic adenosine monophosphate, and disturbances in nucleic acid synthesis and cell cycle kinetics.

8-Chloro-adenosine, the dephosphorylated metabolite of the antineoplastic agent 8-chloro-cyclic AMP, has been proposed to act on the regulatory subunits of cyclic AMP-dependent protein kinase. 8-Chloro-adenosine has a growth-inhibitory effect, the mechanism of which is unclear. We investigated the effects of 8-chloro-cyclic AMP and 8-chloro-adenosine on nucleic acid synthesis and cell cycle kinetics in two human glioma cell lines. These effects were compared to those of the cyclic AMP analogue 8-(4-chlorophenyl)-thio-cyclic AMP (8-CPTcAMP), which is less susceptible to dephosphorylation. Whereas 8-CPTcAMP almost completely inhibited RNA and DNA synthesis, both 8-chloro-adenosine and 8-chloro-cyclic AMP only partly inhibited synthesis of RNA and DNA at growth-inhibitory concentrations, as demonstrated by using [5-1H] uridine and [14C]thymidine incorporation. Therefore, the growth-inhibitory effect of 8-chloro-cyclic AMP is not (or not completely) due to activation of cyclic AMP-dependent protein kinase nor to the inhibition of nucleic acid synthesis. Flow cytometric analysis revealed that 8-chloro-cyclic AMP and 8-chloro-adenosine probably block cell cycle progression at the G2M phase. The effects of 8-chloro-cyclic AMP on nucleic acid synthesis and cell cycle progression were largely prevented by adenosine deaminase, which inactivates 8-chloro-adenosine. This indicates that the effects of 8-chloro-cyclic AMP were at least in part due to its metabolite 8-chloro-adenosine. Incorporation of 8-chloro-adenosine into RNA and DNA might contribute to the disturbance of the cell cycle kinetics and growth-inhibitory effect of 8-chloro-adenosine.

2-Chloroadenosine↗
PubMed1997

Quantitative computer-assisted analysis vs. visual estimation of MR imaging response of brain metastases to radiotherapy.

Using both quantitative computer-assisted analysis and visual estimation the MR imaging response of brain metastases to whole-brain radiotherapy (WBRT) was prospectively studied in 49 patients. Compared to the computer-assisted analysis, the precision of the visual estimation (by two readers in conference) of tumor response was determined. Also the radiological response was related to the clinical response. Six weeks after WBRT follow-up MR was performed in 27 of 49 patients. Of the remaining 22 patients without follow-up MR, 9 had died or deteriorated due to neurologic decline. In four patients (15%) tumor increase was demonstrated by computer-assisted analysis; in the other 23 patients tumor remained stable (15%) or decreased (70%). In 11 of the 27 patients, a second follow-up MR was obtained 26 wk after WBRT demonstrating tumor increase in seven patients (64%). Complete discordance between both assessment methods was noticed in only 4 of 38 MR scans (27 scans 6 wk after WBRT and 11 scans 26 wk after WBRT) with small quantitative changes in tumor volume. In 26 of 38 (68%) observations 6 and 26 wk after WBRT, there was a positive correlation between change in tumor volume and change in the Neurologic Status. Visual estimation analysis seems an appropriate method of routine therapy monitoring in individual patients with brain metastases. The computer-assisted analysis should be considered if precise response monitoring becomes critical.

Adult↗
PubMed1996

In vivo modulation of vincristine-induced neurotoxicity in Lymnaea stagnalis, by the ACTH(4-9) analogue Org 2766.

The use of the cytostatic agent vincristine (VCR) is limited by the occurrence of peripheral neuropathy. This side-effect is probably caused by interference with axonal microtubules. VCR depolymerizes microtubules and reacts with tubulin to form paracrystals. The potential of a neurotrophic ACTH(4-9) analogue, Org 2766, to counteract peripheral neuropathy caused by cytostatic agents is being investigated. In the present ultrastructural study, modulatory effects of Org 2766 on VCR-induced neurotoxicity were studied in vivo in neurons of the pond snail Lymnaea stagnalis, which has been shown previously to be a suitable test system to investigate neurotoxic side-effects of cytostatic agents. 24 h after treatment with VCR (25 microM), 68.4 +/- 34.7 paracrystals were counted per cross-section of the cerebral commissure and the number of microtubules in the axons had been lowered to 46% of the control level. After a survival period of two weeks all paracrystals had disappeared. By that time, no recovery of the axonal microtubular system could be observed. However, post-treatment with Org 2766 (10(-6) M) on day 6 after VCR treatment had induced a significant increase in the number of microtubules (+55%) on day 7. This beneficial effect lasted for the rest of the experimental period (14 days). These results suggest that post-treatment with Org 2766, i.e. after VCR clearance, can induce long-lasting beneficial effects on VCR-induced neurotoxicity in vivo.

Adrenocorticotropic Hormone↗
PubMed1996

Effects of psychiatric consultation on medical consumption in medical outpatients with low back pain.

A randomized, controlled, clinical trial (N = 104) was conducted to test the hypothesis that a protocol of collaboration and communication between neurologist and general practitioner, sustained with psychiatric consultation, would reduce medical consumption (especially of diagnostic procedures and medication) in medical outpatients with low back pain. The intervention was designed at the health care provider level; the psychiatrist did not see or examine the patient. A reduction in medical consumption could not be demonstrated. As there was a great variation in adherence to the protocol in the experimental group, this might explain the lack of hypothesized effects. Full implementation of the protocol seemed to imply a lower number of major surgery operations, but this effect disappeared after excluding cases with a diagnosed hernia. The possibilities for consumption reduction for three post hoc-defined patient categories (cases with hernia and chronic and nonchronic cases) and the consequences for patient selection and treatment intensity are discussed. It is concluded that the target groups should be more narrowly defined, and that a more intensive intervention might prove to be more effective.

Ambulatory Care↗
PubMed1996

Supervised integrated screening of low-back pain patients by a neurologist. A randomized clinical trial.

In a randomized, controlled design, the effect of psychiatric consultation intervention in medical outpatients with low-back pain (N = 104) was assessed for the patients' subjective well-being and satisfaction of general practitioners (GPs) in their cooperation with the neurologists. The goal of the intervention was an integrated approach towards the patients' symptoms and the improvement of the cooperation between primary and secondary medical health services. The intervention was designed at the health care provider level; the psychiatrist did not see or examine the patient. The 104 patients were subdivided into an intervention group (N = 50) and a control group (N = 54). The major outcome measures were the psychological status of the patient and degree of the GPs' satisfaction concerning the cooperation with the medical specialists. After 6 months follow-up, there was a greater overall decline of symptoms in the patient intervention group compared with the control group. However, it was not possible to specify this effect. Contrary to the hypotheses, GPs in the control group were as satisfied about the cooperation with the neurologist as their colleagues in the intervention group. Yet, the information in the specialists' letters of the intervention group was more often in agreement with the integrated model carried out. It is concluded that great diversity of the target group of patients and the focus on the neurologists' behavior may explain the lack of hypothesized effects. It is recommended that the target group be more specifically defined, and that a more intensive intervention might prove to be more effective.

Adolescent↗
PubMed1995

Ultrastructural neuropathologic effects of Taxol on neurons of the freshwater snail Lymnaea stagnalis.

Cerebral ganglia of the freshwater snail Lymnaea stagnalis were incubated in vitro in 10 microM Taxol for 8 and 24 h. Cremophor EL (0.1%) was used as a diluant. The tissue was processed for electron microscopy. Various ultrastructural parameters were assessed quantitatively. Cremophor EL appeared to seriously affect the cell somata of the multipeptidergic caudodorsal cells. In the Cremophor-controls the mean area of Golgi zones, the percentage dense material (neuropeptides) in these zones, the number of large electron dense granules (these are involved in neuropeptide processing) and the mean nuclear heterochromatin clump size, were significantly smaller than in the Ringer-controls, whereas the number of lipid droplets was higher. All these parameters, except for the lipid droplets, were not different in the Cremophor-controls and the Taxol-treated specimens. After 24 h treatment, but not after 8 h, Cremophor EL furthermore induced an increase in the number of axonal microtubules. It is argued that the results might signify activation of the neurons by Cremophor EL. Taxol induced a significant increase in the number of microtubules in axons and cell somata. Furthermore an increase in the number of Golgi zones was observed, suggesting activated neuropeptide synthesis. In all groups immunostaining with antibodies to neuropeptides produced by the caudodorsal cells was normal. Release of neuropeptide (exocytosis) from axon endings was elevated after Taxol treatment, and exceptionally high in specimens cotreated with Taxol and Org 2766 (incubation time 22 h). The effect of Org 2766 and Taxol on the number of microtubules was cumulative.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1995

Endocrine functions in long-term survivors of low-grade supratentorial glioma treated with radiation therapy.

Endocrine functions were studied in long-term survivors of low-grade glioma treated with radiotherapy. Hypothalamic-pituitary dysfunction has recently been reported to occur more frequently than generally considered. Because endocrine dysfunction is a treatable condition, careful testing and, if necessary, supplementary treatment may enhance quality of life. Thirteen adult patients treated with radiotherapy because of supratentorial low-grade glioma at least one year before (range 1-11.5 years) were tested. Focal brain radiotherapy (45-61.2 Gy), with calculated dose to the hypothalamic-pituitary area ranging from 0 to 50 Gy (mean 36.1) had been applied to all patients. Serum levels of pituitary hormones, cortisol and thyroid hormone were determined before and after stimulation with hypothalamic hormones. In 10 out of 13 patients one or more hormonal values were out of the normal range. Most disturbances were demonstrated in the pituitary-adrenal axis (8 patients) and the GH-axis (4 patients). None of the patients had clinical symptomatology of adrenal, thyroid or gonadal dysfunction. Careful endocrine testing after cranial radiotherapy may reveal (subclinical) hypothalamic-pituitary dysfunction in long-term survivors. Follow-up testing in these patients seems warranted.

Adrenal Glands↗