Biomedical subjects

G Cavaletti

Publications and source records attributed to G Cavaletti.

80 records · Page 5Linked to original sources

PubMedDate not supplied

Sural nerve bioptic findings in essential cryoglobulinemic patients with and without peripheral neuropathy.

Peripheral neuropathy often occurs in cryoglobulinemia but the pathogenesis of the peripheral nerve involvement is not completely understood, so that the relation between the reported endoneural changes and neuropathy is not clear. In this study we compared the sural nerve biopsies of 6 cryoglobulinemic patients with or without signs of peripheral neuropathy and all affected by the essential mixed type II form (ECII) and, moreover, of 8 age-matched controls. We found that in all the patients with neuropathy, axonopathy occurred and it was invariably associated with endoneural vessel damage. Moreover, the fiber losses were patchily distributed within the nerve fascicles. On the contrary both nerve fibers and vessels were normal in the patients without clinical and neurophysiological evidence of neuropathy and in controls. Our results support the hypothesis that the endoneural damage observed during ECII is not simply coincidental, but is relevant in the pathogenesis of cryoglobulinemic neuropathy. They also favor the assumption that ischemic damage of the nerve fibers occurs during ECII.

Aged↗

PubMedDate not supplied

Extracorporeal photochemotherapy reduces the severity of Lewis rat experimental allergic encephalomyelitis through a modulation of the function of peripheral blood mononuclear cells.

Extra corporeal photochemotherapy (ECP) is an immunomodulating procedure used in several nonneurological diseases which, similarly to multiple sclerosis, are likely to be due to T-cell-mediated autoimmunity and it is probable that ECP can modulate the normal activity of peripheral blood mononuclear cells (PBMC). Using the Lewis rat experimental allergic encephalomyelitis (EAE) model of human multiple sclerosis (MS) we examined the effect of extracorporeal UV-A irradiation on psoralen-activated PBMC. In our experiment the comparison between the two groups of animals (ECP or sham-treatment) evidenced that the ECP treatment reduced the severity of EAE on clinical grounds and this result was confirmed by the pathological examination. The changes in the titers of anti-myelin antigen antibodies typical of EAE were also modulated by the procedure. Ex vivo examination evidenced a significant reduction in tumor-necrosis factor-alpha (TNF-alpha) released by PBMC after lipopolysaccharides (LPS) stimulation in culture. We conclude that ECP modifies the normal activity of PBMC during the course of EAE and it is possible that one of the anti-inflammatory mechanisms of action of ECP is correlated to a down-regulation of T-helper 1 lymphocytes activity.

Animals↗

PubMedDate not supplied

Intracerebral hemorrhage following intravenous administration of epinephrine.

We report a case of intracerebral hemorrhage (ICH) in a young man following intravenous self-administration of epinephrine. Arteriography evidenced normal intracranial vessels, and namely excluded the presence of vascular malformations which could have been implicated in the pathogenesis of ICH. We believe that the main pathogenetic agent in this case was the sudden rise in arterial blood pressure. This report aims at underlying the severe implications of non-medical use of sympathomimetic drugs.

Adult↗

PubMedDate not supplied

Off-treatment course of cisplatin-induced dorsal root ganglia neuronopathy in rats.

As yet little is known about the off-treatment course of cisplatin (CDDP) neurotoxicity. In this study we evaluated in the rat how the pathological changes in dorsal root ganglia (DRG) neurons and the electrophysiological alterations in peripheral nerves induced by chronic CDDP administration evolved after drug withdrawal. Twelve female Wistar rats were treated with CDDP and 3 of them were sacrificed 1, 5, 10 and 20 weeks after treatment. The results of the experiment indicated that: 1) the damage induced by sub-lethal doses of CDDP in the DRG neurons is reversible, 2) the first structures to be damaged are the DRG neurons (mostly their nucleoli) and 3) both damage and recovery in the follow-up period involve first the DRG neurons and subsequently the peripheral nerves.

Animals↗

PubMedDate not supplied

Long-term peripheral neurotoxicity of cisplatin in patients with successfully treated epithelial ovarian cancer.

We evaluated clinically and neurophysiologically the immediate and long-term involvement of the peripheral nervous system in 22 selected patients with epithelial ovarian cancer successfully treated with DDP alone or in combination with non-neurotoxic drugs. While the motor nerves were unaffected, generally the involvement of sensory nerves was more severe at the examination performed several months after DDP discontinuation than at the evaluation performed after the "induction phase". We conclude that up to now the importance of long-term DDP-induced peripheral nerve damage has probably been underestimated. DDP-induced long-term damage is at least as severe as the immediate toxicity and, moreover, it is likely that complete recovery can occur, if ever, only years after DDP discontinuation.

Adult↗

PubMedDate not supplied

Neuroprotectant drugs in cisplatin neurotoxicity.

Cisplatin (CDDP) is one among the most effective and widely used anticancer drugs. Its use is, however, often limited by its peripheral neurotoxicity, which may be severely disabling and sometimes not reversible. To prevent or reduce CDDP peripheral neurotoxicity several "neuroprotective" drugs have been proposed. This goal is of extreme importance in the treatment of cancer patients, especially in view of the better results obtained by anticancer chemotherapy in terms of longer disease-free survival which has made even more crucial than in the past the point of the quality of life of the long-surviving patients. The data of pre-clinical and clinical studies with neuroprotectant agents are often conflicting, in some cases because of inadequate methods of evaluation and/or study design used to examine their effectiveness. The aims of this review will be 1) to discuss and describe the most appropriate methods of evaluation of CDDP and neuro-protectant drugs in experimental in vitro and in vivo pre-clinical studies 2) to evaluate critically the results of the clinical trials reported so far with the combined treatment and 3) to explore the possible future strategies to achieve neuroprotection during high-dose CDDP treatment in humans.

Adrenocorticotropic Hormone↗

PubMedDate not supplied

Retinoic acid differentiated SH-SY5Y human neuroblastoma cells: an in vitro model to assess drug neurotoxicity.

PURPOSE: To evaluate whether retinoic acid (RA) differentiated human neuroblastoma (HN) SH-SY5Y cells are a suitable and reliable model to test the neurotoxicity of chemotherapic drugs without the confusing effects of the neurotrophic factors commonly used to induce neuronal differentiation. METHODS: Cultures of the SH-SY5Y cell line were exposed to RA to induce neuronal differentiation which was assessed by measuring the neurite length. The effect of increasing concentrations of cisplatin (CDDP) on neurite outgrowth was determined. Cyclophosphamide (CTX) was used as negative control. RESULTS: CDDP induced a significant reduction in the mean neurite length in a dose dependent manner. The neurotoxic effect of CDDP was reversible. Cyclophosphamide did not induce changes in RA differentiated HN cells. CONCLUSIONS: RA differentiated HN cells are sensitive to the neurotoxic effect of CDDP and the course of the changes is similar to that observed in clinical practice and in in vivo experimental models. Therefore, this model is proposed as a screening method to test the neurotoxicity of chemotherapy drugs and the possible effect of neuroprotectant molecules and drugs.

Antineoplastic Agents↗

PubMedDate not supplied

Neuro- and ototoxicity of high-dose carboplatin treatment in poor prognosis ovarian cancer patients.

BACKGROUND: Hematopoietic toxicity of high-dose carboplatin (HD-CBDCA) chemotherapy can be managed effectively with autologous blood cell support, but no conclusive data are available on its neuro- and ototoxicity. PATIENTS AND METHODS: We determined the neuro- and ototoxicity of HD-CBDCA in 10 patients affected by advanced ovarian cancer. HD-CBDCA was delivered as 24-hour continuous infusion or as 5-day schedules. Each patient underwent an extended clinical and instrumental neurological and otological evaluation before, during and after treatment. RESULTS: After HD-CBDCA only 1 patient had a clinically-evident peripheral neuropathy, while 3 additional patients had only distal paresthesias. Neurophysiological examination evidenced mild, although diffuse, sensory nerve impairment. Motor nerve impairment was also occasionally observed. All the sensory and motor pathological changes had a favorable course during the follow-up period. Ototoxicity was more severe than neurotoxicity and, in one case it was dose-limiting and audiologic impairment tended to remain constant also in the follow-up period. CONCLUSIONS: HD-CBDCA treatment can be tolerated by most of the patients, but careful monitoring of neuro- and, especially, ototoxicity should be planned.

Adult↗