Biomedical subjects

C J Vecht

Publications and source records attributed to C J Vecht.

At least 19 recordsLinked to original sources

PubMed2006

A cross-sectional study of subjective complaints in patients with epilepsy who seem to be well-controlled with anti-epileptic drugs.

OBJECTIVES: Side-effects of anti-epileptic drugs (AEDs) may be overlooked in patients with epilepsy in everyday clinical practice. The aim of this study was to assess the prevalence and severity of subjective complaints in patients who were considered to be well-controlled and to assess whether these complaints are related to medication, personality traits, or other determinants. METHODS: We included patients with epilepsy who were considered to be well-controlled in a cross-sectional study in seven hospitals in the Netherlands. Their medication had not been changed for six months and an apparent reason to change the medication was lacking at the time of enrolment. Subjective complaints were assessed with a 46-item questionnaire. Using multivariable linear regression modeling, we assessed whether patient characteristics, epilepsy characteristics, medication, quality of life (Qolie-10), and personality traits (SCL-90) explained the presence and severity of complaints. RESULTS: Of 173 included patients, 67% reported moderate to severe subjective complaints on the questionnaire. Cognitive complaints were reported most frequently. Multivariate modeling showed that 61% of the variance in reported complaints could be explained by included determinants. The prevalence and severity of complaints was associated with AED polytherapy and higher scores on psycho neuroticism. CONCLUSIONS: Patients who were considered to be well-controlled proved to report an unexpectedly high number of subjective complaints. Both medication and aspects of personality contributed to the level of complaints. Our study illustrates that subjective side-effects are easily overlooked in everyday clinical practice, possibly because in practice a generally phrased question is used to detect side-effects.

Adolescent↗

PubMed2003

Second-line chemotherapy with temozolomide in recurrent oligodendroglioma after PCV (procarbazine, lomustine and vincristine) chemotherapy: EORTC Brain Tumor Group phase II study 26972.

BACKGROUND: Oligodendroglial tumors are chemosensitive, with two-thirds of patients responding to PCV combination chemotherapy with procarbazine, lomustine (CCNU) and vincristine. Temozolomide (TMZ), a new alkylating and methylating agent has shown high response rates in recurrent anaplastic astrocytoma. We investigated this drug in recurrent oligodendroglial tumors (OD) and mixed oligoastrocytomas (OA) after prior PCV chemotherapy and radiation therapy. PATIENTS AND METHODS: In a prospective non-randomized multicenter phase II trial patients were treated with TMZ 150 mg/m(2) on days 1-5 in cycles of 28 days for 12 cycles. Eligible patients had a recurrence after prior PCV chemotherapy, with measurable and enhancing disease as shown by magnetic resonance imaging. Pathology and all responses were centrally reviewed. RESULTS: Thirty-two eligible patients were included. In four patients the pathology review did not confirm the presence of an OD or OA. Twelve of 24 patients [50%, 95% confidence interval (CI) 29% to 71%] evaluable for response to first-line PCV chemotherapy had responded to PCV. Temozolomide was in general well tolerated; the most frequent side-effects were hematological. One patient discontinued treatment due to toxicity. In seven of 28 patients (25%, 95% CI 11% to 45%) with histologically confirmed OD an objective response to TMZ was observed. Median time to progression for responding patients was 8.0 months. After 6 and 12 months from the start of treatment, 29% and 11% of patients, respectively, were still free from progression. CONCLUSIONS: TMZ may be regarded as the preferred second-line treatment in OD after failure of PCV chemotherapy. Further studies on TMZ in OD are indicated.

Adult↗

PubMed2001

Involvement of the peripheral nervous system in primary Sjögren's syndrome.

BACKGROUND: Involvement of the peripheral nervous system in patients with primary Sjögren's syndrome (SS) has been reported, but its prevalence in neurologically asymptomatic patients is not well known. OBJECTIVE: To assess clinical and neurophysiological features of the peripheral nervous system in patients with primary SS. PATIENTS AND METHODS: 39 (38 female) consecutive patients with primary SS, aged 20-81 years (mean 50), with a disease duration of 1-30 years (mean 8) were studied. The peripheral nervous system was evaluated by a questionnaire, physical examination, quantified sensory neurological examination, and neurophysiological measurements (nerve conduction studies). To assess autonomic cardiovascular function an orthostatic challenge test, a Valsalva manoeuvre, a forced respiration test, and pupillography were done. RESULTS: Abnormalities as indicated in the questionnaire were found in 8/39 (21%) patients, while an abnormal neurological examination was found in 7/39 (18%) patients. Abnormalities in quantified sensory neurological examination were found in 22/38 (58%) patients. In 9/39 (23%) patients, neurophysiological signs compatible with a sensory polyneuropathy were found. No differences were found in the autonomic test results, disease duration, serological parameters, or erythrocyte sedimentation rate between the patients with primary SS with and those without evidence of peripheral nervous involvement. CONCLUSION: Subclinical abnormalities of the peripheral nervous system may occur in patients with primary SS selected from a department of rheumatology, but clinically relevant involvement of the peripheral nervous system in this patient group is rare.

Adult↗

PubMed2000

[Treatment of posttraumatic dystrophy].

Reflex sympathetic dystrophy, posttraumatic dystrophy or complex regional pain syndrome is a particular type of chronic pain. Although the origin is unknown, some believe that wide-dynamic range neurons located in the dorsal horn of the spinal cord play an essential role. Others consider the role of psychogenic factors underestimated. Until now, controlled clinical trials mainly directed at modulation of the sympathetic system have not revealed clearly effective therapies. Tests with guanethidine, phenylephrine, phentolamine or lidocaine have essentially been negative. Use of low dose glucocorticoids, dimethylsulphoxide, biphosphonates and epidurally applied clonidine require confirmation in studies of larger size. There are indications that invasive electrical spinal cord stimulation may have some effect; randomized studies in patients with posttraumatic dystrophy are needed. So far, only application of physical therapy at an early stage has clearly shown effective pain relief and would also lead to cost reduction.

Humans↗

PubMed2000

Cancer pain: a neurological perspective.

Nerve pain in cancer is common, mainly manifested by a radiculopathy associated with vertebral metastasis, by a plexopathy caused by lymph-node involvement or, more rarely, by trigeminal involvement in cancer of the head and neck. Less frequent types of nerve pain can occur as late effects of antitumour therapy, including surgery, radiation and chemotherapy. The distinction between a nociceptive and a non-nociceptive nerve pain helps in determining the most appropriate symptomatic management.

Humans↗

PubMed2000

Increased incidence of neurological complications in patients receiving an allogenic bone marrow transplantation from alternative donors.

OBJECTIVE: To compare the frequency and type of neurological complications after bone marrow transplantation (BMT) with an HLA identical unrelated donor or a mismatched related donor (alternative donors) to the neurological complications after matched sibling BMT for standard and high risk leukaemia or myelodysplastic syndromes. METHODS: Retrospective analysis of consecutively treated patients with (a) BMT from alternative donors (n=39), (b) treated with matched sibling BMT for standard risk leukaemia, myelodysplastic syndromes, or aplastic anaemia (n=53), and (c) treated with matched sibling BMT for high risk leukaemia, myelodysplastic syndromes, or aplastic anaemia (n=49). RESULTS: A total of 72 neurological complications were found. Most of these occurred within the first 6 months after transplant. Thirty six patients developed a severe neurological complication: 17 Alternative donor patients (44%) by contrast with six standard risk patients (11%) and 13 high risk patients (27%; p<0.005). The most frequent complication was a metabolic encephalopathy occurring in 18% of patients. Most of the encephalopathies were caused by either the transplant procedure, cyclosporin, systemic infections, microangiopathic thrombopathy, or by complications induced by graft versus host disease. Infections of the CNS developed in 9% of patients, cerebrovascular lesions in 3%. CONCLUSIONS: Severe neurological complications are more frequent after BMT from alternative donors. This is mainly due to increased treatment related morbidity and to more profound immunosuppression after BMT from alternative donors.

Adolescent↗

PubMed1999

Distribution of recombinant adenovirus in the cerebrospinal fluid of nonhuman primates.

Gene therapy by administration of vectors into the cerebrospinal fluid (CSF) may be used in treatment of leptomeningeal metastases (cancer gene therapy) as well as in treatment of neurodegenerative disorders, traumatic injury, and chronic pain. Recombinant adenoviruses are attractive vectors for intra-CSF administration because they can efficiently transfer genes into the nonreplicating cells of the central nervous system (CNS). In addition, they can be produced in high titers and, because no producers cells are introduced, the risk of CSF obstruction by clustering cells is circumvented. However, successful application requires favorable distribution dynamics, high transduction efficiency, and long-lasting transgene expression. In this study we examined the distribution of a recombinant adenovirus containing the lacZ gene after administration into the CSF of nonhuman primates. After intraventricular and suboccipital administration, homogeneous distribution of the vector along the meninges covering the brain and spinal cord was obtained, as demonstrated by extensive and intense blue staining of cells, predominantly in the arachnoid and pia mater. In one animal we also found beta-galactosidase activity in the cervical paraspinal fat and in one of the deep cervical lymph nodes, indicating drainage of the vector or vector products with CSF into cervical lymph. This route of vector clearance from the CNS may result in antigenic presentation and an effective immune response and may explain the sixfold higher serum antibody titers after intrathecal injection of adenovirus as compared with intranasal application in Fischer rats. We conclude that distribution dynamics of recombinant adenovirus after intra-CSF administration are excellent. However, because of the immune response elicited by the virus, even after administration to the CNS, development of immunomodulating strategies remains a challenge.

Adenoviridae↗

PubMed1999

Depletion of GDNF from primary afferents in adult rat dorsal horn following peripheral axotomy.

Glial cell line-derived neurotrophic factor (GDNF) is produced in a subset of adult rat spinal ganglion neurons and anterogradely transported to the superficial dorsal horn. In this study the effect of sciatic nerve axotomy on the expression of GDNF protein in the dorsal horn was investigated, using immunocytochemistry. Image analysis showed a 44% decrease relative to the non-transected side after 5 days survival, progressing to more than 80% decrease after 10 days and remaining so for at least 100 days. This rapid and strong decrease suggests active down-regulation of GDNF protein after peripheral axotomy. The observed down-regulation of GDNF is compared with changes observed for other substances in primary afferents after peripheral axotomy and is discussed in light of its presumed trophic or transmitter role in nociception.

Animals↗

PubMed1999

Cyclosporine neurotoxicity: a review.

Cyclosporin A (CsA) induces neurological side effects in up to 40% of patients. A reversible posterior leukoencephalopathy syndrome is the most serious complication. Symptoms include headache, altered mental functioning, seizures, cortical blindness, and other visual disturbances, with hypertension. Neuroimaging studies show white matter changes in the posterior regions of the brain. Other neurological side effects of CsA include tremor, diffuse encephalopathy, cerebellar syndrome, extrapyramidal syndrome, pyramidal weakness, and peripheral neuropathy. Hypertension, hypomagnesemia, hypocholesteremia, and the vasoactive agent endothelin may all play a role in the pathogenesis of CsA neurotoxicty. Neurotoxicity is more frequent with high CsA blood levels, but levels may be within the therapeutic range. Dose reduction or withdrawal of CsA usually results in resolution of clinical symptoms and of neuroimaging abnormalities.

Cyclosporine↗

PubMed1999

The diagnostic accuracy of magnetic resonance imaging and cerebrospinal fluid cytology in leptomeningeal metastasis.

Diagnostic decision making in the case of patients suspected of having leptomeningeal metastasis (LM) can be very difficult. The results of cerebrospinal fluid (CSF) cytology can be repeatedly negative, and the predictive value of gadolinium-enhanced magnetic resonance imaging (MRI) is not well known. We report the results of CSF cytology and Gd MRI in 61 patients with known cancer, suspected of having LM. We combined our data with those from a similar study and calculated the sensitivity and specificity of CSF and Gd MRI, in the absence of a "gold standard diagnosis." CSF cytology was positive for LM in 35 patients and MRI in 38. With CSF cytology sensitivity 75% and specificity 100%, with Gd MRI sensitivity was 76% but specificity only 77%. We conclude that Gd MRI provides strong support in the diagnosis of LM in patients with cancer who have negative results on CSF cytology.

Adolescent↗

PubMed1999

The accumulation of topotecan in 9L glioma and in brain parenchyma with and without dexamethasone administration.

The accumulation of the topoisomerase I inhibitor topotecan in brain tumor as well as in brain around tumor (BAT) and normal brain following an intravenous bolus of topotecan of 0.5 mg/kg was investigated in rats bearing a 9L glioma. Also the influence of dexamethasone (Dex) on the uptake of topotecan was examined. Tumor, BAT and brain tissue as well as whole blood were collected at 1 h after an i.v. bolus of topotecan. Concentrations of total topotecan in tumor, BAT and brain were quantified with high-performance liquid chromatography (HPLC) and compared with concentrations in plasma of total topotecan. In brain tumor tissue the mean total topotecan concentration was 96 +/- 33 ng/g which was 20-fold higher than the accumulation of topotecan in normal brain tissue. In BAT intermediate concentrations of 13 +/- 4.9 ng/g were reached. Mean total topotecan concentration in plasma was 100 +/- 25 ng/ml. We did not find an influence of Dex on the uptake of topotecan in either tissue. We conclude that high tissue concentrations of topotecan can be reached in experimental brain tumors in rats. This observation may be useful in the design of clinical studies with topotecan.

Animals↗

PubMed1999

Phase II study of weekly dose-intensified cisplatin chemotherapy with oral etoposide in recurrent glioma.

BACKGROUND: In most patients with recurrent glioma chemotherapy is the only remaining treatment option. In general results of chemotherapy in these patients are poor, and trials on new regimens are indicated. Because relatively good results have been achieved with combinations of platin compounds and etoposide, we investigated a dose-intensified cisplatin regimen with oral etoposide. METHODS: Eligible patients, with recurrent glioma after surgery and radiation therapy were treated with two four week-cycles with cisplatin 70 mg/m2 on days 1, 8 and 15, combined with oral etoposide 50 mg daily on days 1-15. In responding or stabilized patients, treatment was continued with six four week-cycles of oral etoposide 50 mg/m2 on days 1-21. Toxicity was assessed using the NCI Common Toxicity Criteria, a 50% decrease in contrast enhancing area on MRI scan was considered a partial response. Time to progression was measured from the start of chemotherapy. RESULTS: Sixteen patients were included, 11 were progressive during or immediately after the induction cycles. Two patients achieved a partial response with a time to progression of 42 and 58 weeks. Three patients were stable for 11, 14 and 15 weeks respectively. Toxicity was modest. DISCUSSION: This dose-intensified cisplatin regimen did not result in a significant number of objective responses and even the number of 'stable disease' was small. Given the low response rate of this intensive treatment, we consider this intensive regimen inappropriate for these patients.

Adult↗

PubMed1999

Leptomeningeal metastasis after surgical resection of brain metastases.

OBJECTIVE: To determine the incidence and risk factors for leptomeningeal metastasis after surgery for brain metastasis of solid tumors. METHODS: Review of the records of all patients operated on for brain metastasis between January 1990 and August 1995. RESULTS: In this period 28 patients underwent surgery for brain metastasis, of whom 27 were available for evaluation in this study. Median survival after craniotomy was 11 months. Nine patients (33%) developed leptomeningeal metastasis 2-13 months after surgery, which included six of the nine patients operated on for posterior fossa metastasis (p=0.05). In five patients, leptomeningeal metastasis was the only site of recurrence. Three patients developed the leptomeningeal metastasis as bulky tumour along the spinal cord, which is a rare presentation. No other risk factors for the development of leptomeningeal metastasis other than surgery for posterior fossa metastasis were identified. CONCLUSIONS: There is an increased risk of leptomeningeal metastasis after surgery for posterior fossa metastasis. Future trials should consider the value of an active approach to this complication in these patients.

Adult↗

PubMed1998

Outcome and complications of epidural analgesia in patients with chronic cancer pain.

BACKGROUND: Some cancer patients require invasive techniques for control of chronic cancer pain. Many patients have benefited from local administration of opioids and anesthetics through an epidural catheter. However, epidural abscess and meningitis are side effects of epidural catheters that have serious morbidity and mortality. METHODS: In a retrospective study, the charts of all patients who received an epidural catheter for the management of chronic cancer pain in a 3-year period (1993-1996) were reviewed. Patients with nervous system infections were identified and pertinent clinical, radiologic (magnetic resonance imaging), and bacteriologic data were analyzed. RESULTS: Ninety-one patients received 137 epidural catheters for a total of 4326 catheter days. All but four patients had died at the time of the final analysis. The median survival after placement of the first epidural catheter was 38 days (range, 1 day--> 1000 days). Seventy-two patients received a percutaneous port whereas 19 patients were treated with an implanted subcutaneous port. Adequate pain relief was obtained in 76% of the 58 patients with nociceptive pain and in 73% of 33 patients with neuropathic pain. All neuropathic pain was associated with active tumor and could be classified as nociceptive nerve pain. Technical complications and superficial infections occurred in as many as 43% of patients. Deep infections occurred in 12 patients, 11 of whom had a spinal epidural abscess. CONCLUSIONS: Deep infection is a frequent complication of epidural analgesia and is associated with a high morbidity and mortality. Only cancer patients with a short life expectancy (< or =3 months) should be treated with epidural analgesia.

Adult↗

PubMed1998

Immunocytochemical localization of GDNF in primary afferents of the lumbar dorsal horn.

Immunocytochemistry was used to identify glial cell line-derived neurotrophic factor (GDNF) in rat spinal cord. Strong GDNF labeling was found in fibers and terminals in laminae I and II (outer) and to a lesser extent in the remaining laminae. A few spinal ganglion cells also contained GDNF. After dorsal root transection GDNF disappeared from the dorsal horn and after dorsal root ligation there was accumulation of GDNF only on the ganglion side of the ligation. These findings demonstrate anterograde transport of GDNF within primary afferent fibers, which constitute the only source of GDNF labeling in the dorsal horn. The strong presence of GDNF in the superficial dorsal horn may indicate that GDNF has a role in pain transmission in the adult rat spinal cord.

Animals↗

PubMed1998

[Immunology in the clinical practice. XVI. Paraneoplastic syndromes of the nervous system: pathogenesis and diagnosis].

Paraneoplastic neurological syndromes are believed to result from ectopic expression of onconeural antigens by tumours. The resulting immune response is not only directed against the tumour but also cross-reacts with the same or similar antigens in the nervous system. The immune response generates high titred autoantibodies that are associated with specific tumours and neurological syndromes. Paraneoplastic autoantibodies help diagnose neurological syndromes and help direct the search for an underlying tumour. In paraneoplastic syndromes, the course of the tumour is relatively mild. Detection of the autoantibodies might lead to early diagnosis and immunomodulation and anti-tumour treatment before irreversible neuronal cell loss and deficits set in.

Antibodies, Neoplasm↗

PubMed1998

[Immunology in medical practice. XIV. Central nervous system complications in systemic autoimmune diseases].

Complications of the central nervous system (CNS) are common in systemic autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus (SLE) and primary Sjögren's syndrome. Specific diagnostic tests are lacking and early intervention with immunosuppressive therapy is frequently necessary. Therefore knowledge of these CNS complications is essential for early diagnosis and treatment. Residual cognitive effects were observed in some but not in all tests after prolonged heavy cannabis use. The effects were mostly mild. The relationship of cannabis use, psychotic effects and schizophrenia was unclear; the cannabis conceivably gave relief, but it also appeared that cannabis caused schizophrenia in young people and (or) enhanced the symptoms, especially in young people poorly able to cope with stress or in whom the antipsychotic therapy was unsuccessful.

Arthritis, Rheumatoid↗

PubMed1998

Clinical management of brain metastasis.

Brain metastasis is a common complication occurring in about 15-20% of all cancer patients. For the initial management, distinguishing between three types of presentation is essential: de novo brain metastasis, simultaneous presentation of both brain metastasis and the primary tumour (usually lung carcinoma), and the presentation of a patient known to have systemic cancer developing a brain metastasis. For de novo brain metastasis, surgery is required, and detecting the primary tumour is of limited value. For simultaneous presentation, both a craniotomy and a thoracotomy may be indicated and may lead to cure in a number of cases. For a sequential presentation, the outcome is determined by a number of independent prognostic factors: age, performance status, and the extent of metastatic disease. In relatively young patients with a single brain metastasis, good performance status and no progression of systemic disease, treatment by either surgery or radiosurgery in combination with whole brain radiation therapy is indicated. Otherwise, as in multiple brain metastases, radiation therapy only is the main treatment. For symptomatic therapy of brain oedema or increased intracranial pressure, dexamethasone is administered. The standard doses of dexamethasone may vary between 4 and 16 mg/day, depending on the severity of symptoms.

Anticonvulsants↗