PubMed Health⌕ Search

Biomedical subjects

J J Heimans

Publications and source records attributed to J J Heimans.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Assessment of quality of life in patients treated for low-grade glioma: a preliminary report.

In this pilot study quality of life was assessed in fourteen adult patients who were treated for a low-grade glioma with surgery and radiotherapy at least one year previously. Apart from widely used parameters, such as the neurological and functional status, the patients' cognitive functioning and actual affective status were determined. In addition the patients were interviewed to evaluate various aspects of quality of life. Generally no serious focal neurological deficits were found, although psychological examination showed serious cognitive and affective disturbances in most cases. Self report measures concerning cognitive functioning were not in all cases in accordance with objective test results. When the results of treatment in glioma patients are evaluated assessment of quality of life, including neuropsychological functioning, should be performed, especially as new therapeutic strategies are being developed.

Activities of Daily Living↗
PubMed1992

Suramin: rapid loading and weekly maintenance regimens for cancer patients.

PURPOSE: Suramin is an anticancer agent with a narrow therapeutic window and a terminal half-life of 45 to 55 days. These characteristics make it necessary to control accurately the serum concentrations of the drug. Therefore, the aim of the present study was to develop a rapid loading regimen, followed by weekly administration of suramin to maintain serum concentrations of between 150 and 300 micrograms/mL for 8 weeks. PATIENTS AND METHODS: Eligible patients were treated with five different loading regimens. Initially, weekly maintenance doses were estimated manually by the treating physician. Subsequently, computer-assisted dosing that used Bayesian pharmacokinetic modeling was used. RESULTS: Thirty-eight courses of suramin that were administered to 35 patients were studied. The optimal loading regimen consisted of a continuous infusion of 600 mg/m2 during a 24-hour period, which resulted in a mean serum concentration of 319 micrograms/mL. Potentially toxic concentrations that were observed with shorter infusions were avoided. Maintenance treatment, which used the weekly administration of suramin during a 6-hour period, seemed to be able to maintain mean suramin serum trough concentrations of 150 micrograms/mL, while preventing mean peak concentrations of more than 300 micrograms/mL. The use of Bayesian pharmacokinetics was superior to manual estimation in tailoring the optimal dose to the therapeutic window. CONCLUSIONS: Continuous infusion is the optimal way of delivering suramin during the loading phase. To maintain trough levels and peak levels within a narrower therapeutic window, suramin will have to be administered more frequently than once a week. Bayesian modeling based on individual serum levels and population pharmacokinetics allows accurate dosing to maintain suramin levels within the therapeutic window.

Adult↗
PubMed1992

Do metastases in vertebrae begin in the body or the pedicles? Imaging study in 45 patients.

We analyzed CT scans of the spine obtained in patients with vertebral metastases to determine what specific portion of the vertebra is initially involved by metastasis. The CT findings were then correlated with the abnormalities seen on plain films. Forty-five patients with histologically proved metastases in 95 vertebrae were included in the study. In all patients, CT scans and plain films of the spine were obtained within 1 week of each other. Analysis of the CT scans showed that the vertebral body was the portion of the vertebra that was most frequently destroyed by the metastases. Destruction of a pedicle was never identified in the absence of involvement of the body. The opposite was true on plain films, in which the most common finding was destruction of the pedicles. CT showed that the position of the metastases in the vertebra correlated with the sites of entry of the vertebral vessels. Our results show that the initial anatomic location of metastases within vertebrae is in the posterior portion of the body. Analysis of CT scans shows that the body is involved before the pedicles, although destruction of the pedicles is the most common finding on plain films. The pedicles are not the primary site of metastatic involvement. Destruction of the pedicles occurs only in combination with involvement of the vertebral body.

Adult↗
PubMed1991

The cause of increased pupillary light reflex latencies in diabetic patients: the relationship between pupillary light reflex and visual evoked potential latencies.

In 42 diabetic patients the relationship between the latency of the pupillary light reflex and the pattern reversal visual evoked potential (P100) was examined. Fifty-five percent of diabetic patients had pupillary light reflex latencies above the normal range. In 19% the visual evoked potentials were prolonged when compared to the normal range. Latencies of pupillary light reflexes and VEPs showed no correlation. There was a minimal correlation between the presence of retinopathy and prolongation of both the pupillary light reflex and the visual evoked response latency (kappa coefficients respectively: 0.31, P less than 0.01 and 0.36, P less than 0.02). The presence of an increased pupillary light reflex latency was positively correlated with a reduced respiratory sinus arrhythmia (kappa coefficient: 0.58, P less than 0.0001). Increased VEP latencies showed no correlation with signs of cardiovascular autonomic neuropathy. We conclude that the afferent optic pathway can be affected in diabetic patients. However, prolongation of pupillary light reflex latency in diabetic patients is primarily due to an efferent pupillary defect and represents parasympathetic dysfunction.

Adult↗
PubMed1991

Cardiovascular autonomic function in multiple sclerosis.

In this study blood pressure (BP) and heart rate (HR) responses to standing and HR responses to deep breathing were assessed in 34 patients with clinically definite multiple sclerosis (MS) and 63 healthy subjects. Normal ranges, which were clearly age related for both HR responses, were obtained. The BP response to standing was abnormal in 13% of the MS patients, these patients demonstrating significant postural hypotension. The HR response to standing was abnormal in 28% of the MS patients, with a normal initial increase in heart rate and a significantly reduced reflex bradycardia. On deep breathing 36% of MS patients showed abnormal HR changes. The resting HR did not differ between both groups. Abnormalities of one or more tests were found in 53% of the MS patients. No relationship was found between abnormal cardiovascular autonomic responses and the symptoms, duration, severity and progression of the disease. Based on clinical and magnetic resonance imaging findings no indications were found for localisation of the autonomic disturbances in the brainstem. It is suggested that at least a part of the cardiovascular autonomic lesions in MS is located outside the brainstem, i.e. in supramedullary reflex pathways or in the spinal cord.

Adult↗
PubMed1991

Treatment of leptomeningeal carcinomatosis with continuous intraventricular infusion of recombinant interleukin-2.

A 42-year-old man developed leptomeningeal carcinomatosis 6 years after treatment of a malignant melanoma. He was treated with two courses of recombinant interleukin-2, administered as a continuous intraventricular infusion (6 X 10E5 U/24 h) during 5 days. During the first day of the first course he also received 5 X 10E9 lymphokine-activated killer cells intraventricularly. This gave rise to a severe elevation of intracranial pressure, with headaches and meningismus. During the second course no LAK cells were administered. This course was tolerated much better. The neurological status did not change during the treatment. Recombinant interleukin-2 levels were maintained at about 300 U/mL during both courses.

Adult↗
PubMed1991

Cold and warm cutaneous sensation in diabetic patients.

The assessment of cutaneous thresholds for thermal sensation is now recognized as a valuable method to detect small nerve fibre function in diabetes. Methods commonly used do not allow separate measurements of warm and cold perception. However, there is evidence that the fibre subtypes which signal cold and warm sensation are different (A-delta-fibres and C-fibres, respectively). To investigate if diabetes affects cold and warm sensation equally, thresholds were assessed separately in 30 diabetic patients (age 47.9 +/- 15.1 (+/- SD) years; duration of diabetes, 19.1 +/- 13.3 years). Comparisons were made with 71 non-diabetic control subjects (age 59.7 +/- 22.1 years). Thermal discrimination thresholds for cold and warm sensation were determined for the left foot with a two-alternative forced choice method. In both diabetic patients and in the control group cooling thresholds were smaller than warming thresholds. In diabetic patients log thermal discrimination thresholds for warmth increased 0.1 per decade (p less than 0.001), a relationship comparable to that seen in non-diabetic patients. There was no relationship between cooling thresholds and age in diabetic patients despite a significant (p less than 0.001) deterioration with age in control subjects. This difference in the influence of age on cold sensitivity was significant (p less than 0.03). Both warm and cold sensation were not related to the duration of diabetes. We conclude that assessment of warm threshold is preferred for the detection of minor disturbances of small nerve fibre function in diabetes.

Adult↗
PubMed1991

Cyclandelate in diabetic neuropathy. A double-blind, placebo-controlled, randomized, cross-over study.

Cyclandelate has the ability to improve the rheological properties of the blood and therefore may improve blood supply of peripheral nerves. Previous studies in diabetic neuropathy have shown beneficial effects of the drug. We performed a double-blind, placebo-controlled, cross-over study in 40 diabetic patients with cyclandelate in a dose of 1600 mg daily. Motor and sensory nerve conduction velocities, late responses, thermal discrimination thresholds, vibration perception thresholds and pain scores were studied. We were not able to show any positive effect of the drug and therefore conclude that cyclandelate is not effective in the treatment of diabetic neuropathy.

Adult↗
PubMed1990

Prevention of cisplatin neurotoxicity with an ACTH(4-9) analogue in patients with ovarian cancer.

In a randomized, double-blind, placebo-controlled study, we assessed the efficacy of an ACTH(4-9) analogue, Org 2766, in the prevention of cisplatin neuropathy in 55 women with ovarian cancer. The analogue was given subcutaneously in a dose of 0.25 mg (low dose) or 1 mg (high dose) per square meter of body-surface area before and after treatment with cisplatin and cyclophosphamide (75 and 750 mg per square meter every three weeks). The threshold of vibration perception was used as the principal measure of neurotoxicity. After four cycles of chemotherapy, the mean (+/- SEM) threshold value for vibration perception in the placebo group increased from 0.67 +/- 0.12 to 1.61 +/- 0.43 microns of skin displacement (P less than 0.0001). In the high-dose treatment group, there was no increase in the threshold value after four cycles (from 0.54 +/- 0.12 to 0.50 +/- 0.06 micron). After six cycles of chemotherapy, the threshold value was 5.87 +/- 1.97 microns in the placebo group (more than an eight-fold increase from base line), as compared with 0.88 +/- 0.17 micron (less than a twofold increase) in the high-dose treatment group (P less than 0.005). In the high-dose group, fewer neurologic signs and symptoms were recorded than in the placebo group. With the lower dose of the analogue, these protective effects were less prominent. No side effects were seen after treatment with Org 2766. The rates of clinical response to chemotherapy were similar in all groups. These results suggest that Org 2766 can prevent or attenuate cisplatin neuropathy without adversely affecting the cytotoxic effect of the drug.

Adrenocorticotropic Hormone↗
PubMed1990

Accuracy and interobserver variation in the interpretation of computed tomography in solitary brain lesions.

The clinical data and computed tomographic findings of 64 patients with solitary supratentorial brain lesions were presented to two panels of six experienced clinicians. The diagnoses predicted by these clinicians were compared with each other (interobserver variation) and with the definite diagnosis, which in almost all cases was based on histologic examination of the involved tissue (validity of predicted diagnosis). The interobserver agreement was only moderate. The predicted diagnoses agreed with the definite diagnoses in only 57% of cases. A high number of errors were made in distinguishing between high-grade and low-grade glioma and between high-grade glioma and cerebral metastasis, and in the detection of primary cerebral lymphoma. Possible implications of these findings for clinical practice are discussed.

Adult↗
PubMed1990

Longterm meningeal involvement as the only clinical manifestation of low grade malignant non-Hodgkin's lymphoma.

We present the case of a 56-year-old man who developed-at the age of 46-paraesthesia and numbness in the perianal region, the feet and lower legs accompanied by the presence of B-lymphocytes in the cerebrospinal fluid (CSF). Despite intensive work-up an explanation was not found until he developed hepato-splenomegaly ten years after the initial symptoms. Haematologic evaluation at that time disclosed a low-grade malignant B-cell lymphoma. Repeated CSF examination revealed 31 leukocytes/mm3, of which were mainly lymphocytes. These proved to be B-lymphocytes of monoclonal origin. These findings suggest that a leptomeningeal localisation of a low-grade malignant lymphoma had been present for ten years before systemic manifestation of the disease.

Adult↗
PubMed1990

Assessment of pupillary light reflex latency and darkness adapted pupil size in control subjects and in diabetic patients with and without cardiovascular autonomic neuropathy.

Increased pupillary light reflex latencies were found more often than a reduced darkness pupil size in diabetic patients with and without abnormal cardiovascular reflexes. This finding suggests that parasympathetic pupillary dysfunction precedes sympathetic pupillary denervation in diabetic autonomic neuropathy.

Adolescent↗
PubMed1989

The relationship of cold and warmth cutaneous sensation to age and gender.

To evaluate cold and warmth cutaneous sensation separately, thermal discrimination thresholds (TDTs) for the foot were estimated for cold and warm stimuli in 71 normal subjects aged between 21 and 92 years. A "thermoaesthesiometer" operating on the Peltier principle was used. A rise of TDTs with age was found. Furthermore, female subjects appeared to have lower thresholds than males. Independent of age or gender, TDTs for cold stimuli were on average lower than for warm stimuli. In accordance with other studies, a large intraindividual variability was found, which emphasizes the necessity for repeated measurements.

Adult↗