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Biomedical subjects

C J Vecht

Publications and source records attributed to C J Vecht.

At least 73 records · Page 4Linked to original sources

Effect of age on treatment decisions in low-grade glioma.

The proper treatment of low-grade glioma is unclear and major uncertainties include the timing of therapy, the need for extensive surgery, or the application of radiotherapy. Although prospective trials are in progress, it may be years before results become available, as the five-year survival of low-grade glioma is around 45% or more. Age is an important prognostic factor in malignant glioma, but its implications for decisions on treatment have not yet been addressed in guidelines. This review examines the interaction between age and the results of applied treatment, based on data from published series. The available evidence suggests that, in younger patients, whether treatment is started early or late does not seem to affect long-term survival substantially. For patients under 35 years of age, more radical surgery appears to be beneficial, while radiation does not seem to improve the outcome. For patients who are 35 years and older, surgery and radiotherapy seems to produce better survival rates. The age of the patients should therefore be considered when decisions on the treatment of supratentorial, non-pilocytic, low-grade gliomas. For patients under 35 years of age who have either epilepsy or a surgically inaccessible tumour, it is advisable to defer treatment. The tumour should be largely excised, if possible. Following any surgery, radiotherapy should be withheld in this age group. For patients over 35 years of age, early treatment, including biopsy or surgery followed by radiotherapy, should not be delayed. Because of more prolonged survival, and to prevent neurotoxicity, radiation fields should be limited to the tumour bed and not include the whole of the brain. Future trials need to establish whether age is a crucial factor in deciding the timing and extent of treatment in patients with low-grade glioma.

Adult↗

Antineuronal antibodies in patients with neurologic complications of primary Sjögren's syndrome.

Neurologic complications of both the central and peripheral nervous systems occur frequently in patients with primary Sjögren's syndrome (primary SS), but the underlying cause of these complications is unknown. We studied the presence of antineuronal antibodies in relation to neurologic complications in a consecutive series of 45 patients with primary SS. Twenty-five patients had neurologic complications: 12 patients with polyneuropathy, three with psychiatric disorders, four with carpal tunnel syndrome, seven with migraine, seven with myalgia, and four with other complications (transverse myelitis, stroke, Bell's palsy, and pyramidal signs). Ten patients had more than one neurologic complication. Eleven patients had major and 14 had minor complications according to criteria used for rating neurologic complications in patients with systemic lupus erythematosus. Antineuronal antibodies were present in six of 11 (55%) patients with major neurologic complications and in four of 34 (11%) of patients without major neurologic complications (p = 0.001). This difference could be attributed mainly to the group of patients with polyneuropathy. Three of the 10 sera of patients with positive antineuronal antibodies had antibodies reacting with a 38-kd neuronal protein on immunoblotting, identical to the anti-Hu antibody reactivity in paraneoplastic neurologic disease associated with small-cell lung cancer.

Adult↗

Types and causes of pain in cancer of the head and neck.

In a series of 25 patients with head and neck cancer who had severe pain, the type and cause of the pain were analyzed. There were two types of pain: nociceptive and non-nociceptive. Nineteen (76%) patients had nociceptive pain that could be subdivided into actual nociceptive pain (9 patients), nociceptive nerve pain (8 patients), or referred pain (2 patients). The cause of nociceptive pain was secondary to tumor recurrence in 16 patients and secondary to benign inflammation in 3 patients. Of the six (23%) cases of non-nociceptive pain, all were diagnosed as neuropathic pain secondary to the sequels of neck dissection. World Health Organization guidelines were applied for the treatment of symptomatic pain of nociceptive pain; if necessary, nerve blocks were used after this treatment. Non-nociceptive pain was usually treated with amitriptyline or carbamazepine. If tumor recurrence was the cause of the pain, antitumor-directed therapy was applied, when possible. Relief was achieved in 52% of the patients after two attempts to treat pain, in 64% after three attempts, and in up to 72% after four attempts. Pain could not be controlled in 28% of the patients. Patients with tumor recurrence had a short median survival time of 3 months, regardless of pain control. Patients with neuropathic pain had a survival time of 16 months or more (median not reached). The authors conclude that the type and cause of the pain in cancer of the head and neck can be determined; this can lead to the administration of proper symptomatic therapy or treatment directed at the underlying cause. In most cases, several successive attempts to treat pain were made before relief was achieved.

Analgesics↗

The course of neuropathy after cessation of cisplatin treatment, combined with Org 2766 or placebo.

Peripheral neuropathy is an important and disabling side-effect of cisplatin treatment. A new drug, Org 2766, has been found to prevent this neuropathy up to 1 month after treatment. A group of 18 patients with ovarian cancer, who participated in an earlier randomized study with placebo or Org 2766, together with cisplatin and cyclophophamide, were thereafter prospectively followed up to 2 years after discontinuation of treatment to monitor the development of neurological signs and symptoms and vibration perception threshold (VPT). Exploratory, descriptive data analysis shows that between 1 and 4 months after the last cycle the average sum score for neurological signs and symptoms and VPT had deteriorated compared with 1 month after treatment. Thereafter a gradual but incomplete improvement was seen between 4-12 and 12-24 months after treatment. These changes were seen in all patients regardless of previous treatment with Org 2766 or placebo, but deterioration was less pronounced in patients previously treated with Org 2766. These results suggests that treatment with Org 2766 to prevent a cisplatin-induced neuropathy should possibly be continued up to 4 months after the last cycle of cisplatin.

Adrenocorticotropic Hormone↗

ACTH/MSH like peptides in the treatment of cisplatin neuropathy.

The neurological toxicity seen in patients treated with cisplatin in most cases concerns ototoxicity and peripheral neuropathy. Thus far, the pathogenesis of cisplatin neuropathy remains obscure. Yet the fact that cisplatin affects mainly the sensory peripheral nerve fibers points towards an involvement of the dorsal root ganglia. In a rat model of cisplatin neuropathy, following a cumulative dose of approx. 12 mg/kg cisplatin the sensory nerve conduction velocity began to slow as compared to age-matched controls. Peptides derived from ACTH and MSH are known to exert neurotrophic effects. In vivo they facilitate postlesion repair mechanisms in the peripheral nervous system by enhancing the early sprouting response of the damaged nerve. Surprisingly, chronic treatment with a synthetic ACTH4-9 analog not only prevented cisplatin neurotoxicity following a low or high dose regimen, but also counteracted already existing cisplatin-induced neurotoxicity. Stimulated by these findings a randomized, double blind, placebo-controlled study was performed to assess the efficacy of the peptide in the prevention of cisplatin neuropathy in women suffering from ovarian cancer. The threshold of vibration perception (VPT) was used as the principal measure of neurotoxicity. Following 6 cycles of chemotherapy the VPT had increased more than 8-fold in women receiving placebo as co-medication. Whereas the VPT in women receiving 1 mg/m2 body surface ACTH4-9 analog before and after each cisplatin cycle only increased less than 2-fold. No side effects of the peptide treatment were observed and the clinical response to the chemotherapy was similar in all treatment groups. Collectively these preclinical and clinical data suggest that treatment based on non-endocrine fragments of ACTH/MSH may be a therapeutic option in the treatment of cisplatin neuropathy.

Adrenocorticotropic Hormone↗

The pleomorphic xanthoastrocytoma and its differential diagnosis: a study of five cases.

Five brain tumors with the histopathologic features of pleomorphic xanthoastrocytomas (PXAs) are presented. Computed tomography scans showed a remarkable homology. Two cases had atypical localizations for a PXA, while one 46-year-old patient did not conform to the normal age distribution of this tumor. Nevertheless, in these cases, the histopathology was always characteristic for PXA, a remarkable pleomorphism, in addition to simultaneous expression of glial fibrillary acidic protein and histiocytic markers in the various tumor cells. In one of the presented tumors, however, clusters of neoplastic neuronal cells were also found. In this particular case, differential diagnostic criteria to distinguish between a PXA and a desmoplastic infantile ganglioglioma are lacking.

Adolescent↗

Phase I study of DABIS maleate given once every 3 weeks.

DABIS maleate is an alkylating quaternary nitrogen. In a phase I study DABIS maleate was administered as a single intravenous infusion once every 3 weeks. 32 patients with solid tumours were studied, at least 3 per dose level (50-1400 mg/m2). Dose-limiting toxicity was severe paresthaesias in the face, around the mouth and in the tongue. Cerebellar ataxia developed at 750 mg/m2 or higher. Haematological toxicity was minimal. Nausea and vomiting were mild to moderate. No other non-haematological side-effects were noted. The recommended dose for phase II studies at once every 3 weeks is 750 mg/m2 intravenously as a 15 min infusion.

Adenocarcinoma↗

Polyneuropathy as initial manifestation of necrotizing vasculitis and gangrene in systemic lupus erythematosus.

A patient with necrotizing vasculitis and systemic lupus erythematosus is reported. The vasculitis presented as a symmetrical sensorimotor axonal neuropathy and after three months it resulted in gangrene of a toe. Sural nerve conduction was abnormal and a biopsy of this nerve was diagnostic. Serum anti-endothelial cell antibodies were elevated during activity of the vasculitic process. Treatment with prednisone and cyclophosphamide induced a remission.

Adult↗

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↗