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Biomedical subjects

L Durelli

Publications and source records attributed to L Durelli.

At least 55 records · Page 3Linked to original sources

Immunotherapeutics of multiple sclerosis.

Immunosuppressive therapy may act specifically by inhibiting a certain stage of the immune response, or, by contrast, by inducing an overall inhibition of the immune system. Low dosage, a specific immunosuppressive therapeutic protocols with corticosteroids or azathioprine are used routinely, although there is no evidence of their effects. There are, however, unquestionable data on the numerous (and serious) side effects. High dosage, a specific immunosuppression appears to be better tolerated (probably due to the brevity of the treatment) and to have certain immunodepressant effects within the CNS. ACTH and methylprednisolone are recommended for short-term relapse therapy. Specific immunosuppressive treatment will no doubt be part of future autoimmune disease therapy, but for the time being is no more than theoretically stimulating experimentation (anti-idiotypic monoclonal antibodies, specific T cell suppressor factor, T cell "vaccination"). Important multicentric studies on cyclosporin-A and copolymer 1 are almost complete on the numerous side effects as regard to cyclosporin-A. Clinical trials with alpha or beta-interferons are still in progress and, so far at least, these drugs appear to be characterized by the absence of important side effects.

Antibodies, Monoclonal↗

Increased thymocyte differentiation in myasthenia gravis: a dual-color immunofluorescence phenotypic analysis.

Thymocytes express multiple, different surface antigens according to their stage of maturation. Surface differentiation antigens have been studied with the technique of simultaneous dual-color, direct immunofluorescence in the thymuses of 20 patients with myasthenia gravis (MG) and 10 control subjects with cardiac diseases. Fluorescein isothiocyanate-conjugated and phycoerythrin-conjugated monoclonal antibodies were used to stain thymic cell suspensions. A significant decrease in the percentage of immature and common thymocyte phenotypes (CD1+,3+ and CD4+,8+) and a significant increase in the percentage of mature thymocyte phenotypes (CD1-,3+; CD4+,8-; and CD4-,8+) and of B cells (CD20+) were found in MG thymuses compared with controls. These data, indicating an increased availability of mature, fully immunocompetent T and B cells, indirectly suggest the occurrence of an active immune response in MG thymus.

Adult↗

High-dose intravenous methylprednisolone in the treatment of multiple sclerosis: clinical-immunologic correlations.

We conducted a double-blind trial of high-dose parenteral 6-methylprednisolone (MP) and placebo on 23 patients with acute MS. After the double-blind trial, the patients were given corticosteroids in gradually decreasing doses. The frequency of improvement was significantly higher and the bout duration significantly lower in the MP group than in the placebo group. The first signs of improvement (3 to 6 days after starting MP) were associated with a marked decrease in the rate of CNS IgG synthesis, but IgG CSF oligoclonal bands did not change. CNS IgG production slowly returned toward baseline despite progressive clinical improvement.

Adult↗

Cardiac side effects of phenytoin and carbamazepine. A dose-related phenomenon?

Three patients with dystrophia myotonica and echocardiographic signs of subclinical cardiopathy had cardiac side effects during oral treatment with phenytoin sodium or carbamazepine. These side effects were dose related: ventricular tachycardia appeared at a toxic serum phenytoin level in one patient and disappeared as the concentration fell within the therapeutic range, and atrioventricular block grade 1 developed in two patients at low serum carbamazepine levels, its severity increasing with the drug level. Given the risk of dangerous side effects, cardiac status needs to be carefully assessed before administration of phenytoin or carbamazepine in the treatment of dystrophia myotonica.

Adult↗

A syndrome resembling limbic encephalitis, associated with bronchial carcinoma, but without neuropathological abnormality: a case report.

A patient, suffering from an oat-cell bronchial carcinoma, presented with complex partial seizures, complete loss of recent memory, mild disorientation and confabulation. There was no complaint of anxiety. The rest of the neurological examination and four computed tomographic scans of the head were normal. Repeated EEG recordings were abnormal. Antiepileptic and antipsychotic treatment led to full remission within 10 days. Post-mortem examination of the brain revealed no pathological changes.

Carcinoma, Bronchogenic↗

[Hypokalemic myopathy caused by fluoroprednisolone in a nasal spray. Observations 2 cases].

Reference is made to the picture observed in two patients with flaccid tetraparesis, severe hypopotassaemia, and myoglobinuric muscle necrosis (hypokalaemic myopathy). Recent onset of hypertension was a feature of both cases. Initially, however, no reason could be assigned for this, nor for the massive loss of potassium. Numerous investigations in the first case (and relatively quick verification in the second) incriminated a steroid, 9-alpha-fluoroprednisolone acetate, in a nasal spray. This has often been reported as the cause of an iatrogenic syndrome due to excess of mineral corticoids, with hypertension, hypokalaemia and alkalosis, suppression of plasma renin activity, and reduction of blood and urinary aldosterone, all of which were observed in these two patients. Withdrawal of the drug and treatment with potassium chloride led to relatively rapid normalisation of the serum electrolytes. Recovery of muscle strength took place after about 20 days, almost at the same time as the normalisation of muscle enzymes. Hypertension, on the other hand, regressed slowly. The nexus between chronic use of the spray and the occurrence of hypokalaemic muscle necrosis is examined in detail. Stress is laid on the importance of specific investigation of the prior use of intranasal steroids in the differentiation of muscle disturbances due to potassium depletion.

Administration, Intranasal↗

The quantification of myotonia. A problem in the evaluation of new antimyotonic drugs.

The evaluation of an antimyotonic drug is often difficult since the severity of myotonia is itself hard to assess. The rise in arterial potassium level produced by the infusion of increasing concentrations of potassium chloride brought about reproducible changes in the excitability level of myotonic muscles proportional to the plasma potassium concentration. The excitability changes were assessed by three methods commonly used for evaluating antimyotonic drugs. The duration of the electromyographic relaxation time after maximal voluntary effort proved to be the only test which reliably assessed the variations of muscular excitability proportional to the increased plasma potassium. By contrast, the duration of percussion- or electrically-induced myotonic after-discharges was extremely variable and independent of plasma potassium.

Electric Stimulation↗

The current status of taurine in epilepsy.

The part played by taurine in epileptogenesis is still controversial. A cortical deficit of the amino acid has been confirmed only in certain types of human and animal epilepsy, and the effects of an artificial change of taurine cortical concentration are inconclusive. An increase is associated with a reduced susceptibility to epileptogenic agents but not with the prevention of epilepsy, while a decrease may precipitate seizure activity in genetically susceptible rats but does not bring about spontaneous epileptic activity in normal animals. The role of taurine in synaptic transmission is uncertain (specific inhibitory neurotransmitter, indirect modulator of membrane excitability), and its antiepileptic action, confirmed in several models of experimental epilepsy and in short-term clinical studies, does not seem to possess major clinical relevance since trials with a longer follow-up gave unsatisfactory results. Taurine's limited diffusibility across the blood-brain barrier may be the main factor restricting the antiepileptic effect of this compound.

Animals↗

Carbamazepine versus diphenylhydantoin in the treatment of myotonia.

A double-blind controlled trial was performed on 6 patients affected with Steinert's disease in order to evaluate the efficacy of two different dosages of diphenylhydantoin (PHT, 200 and 300 mg/day) and carbamazepine (CBZ, 600 and 800 mg/day) on the myotonic afterdischarge. Both dosages of PHT and CBZ induced a significant improvement of myotonia. For PHT a trend towards decreased efficacy is pointed out at toxic or at high dosages.

Adolescent↗

The treatment of myotonia: evaluation of chronic oral taurine therapy.

A double-blind, single crossover study of chronic oral taurine administration versus placebo was conducted on nine patients with dystrophia myotonica. The severity of myotonia was assessed by clinical and electromyographic criteria and by testing the sensitivity of myotonic muscles to the intra-arterial infusion of potassium chloride. Confirming the antimyotonic effect of acute parenteral taurine, chronic treatment induced significant improvement of myotonia and a decreased sensitivity to the arterial potassium load as well as an enhancement of electrolyte movements across the membrane of the studied muscles. No significant side effects were noted.

Administration, Oral↗

Taurine and hyperexcitable human muscle: effects of taurine on potassium-induced hyperexcitability of dystrophic myotonic and normal muscles.

Progressively increasing concentrations of potassium chloride in Evans blue saline were administered to patients affected with myotonic dystrophy and to healthy volunteers before and after parenteral treatment with taurine. Excitability changes of thenar eminence muscles were related to the venous potassium and chloride concentrations. The actual electrolyte concentrations were compared to those to be expected if no infused electrolytes had been transported into cells. The expected concentrations were calculated by means of Evans blue dilution. This method permitted quantification of changes of muscle-excitability in terms of the potassium chloride concentration capable of disturbing the electrical activity of the studied muscles. The method also provided an indirect evaluation of electrolyte movements across muscle membrane in vivo in humans. Dystrophic myotonic muscles appeared highly sensitive to extracellular potassium and, unlike normal muscles, were unable to accumulate potassium-induced muscle hyperexcitability and favored electrolyte accumulation in dystrophic myotonic muscles. The stabilizing effect of taurine is discussed in relation to its ability to increase intracellular potassium concentration, membrane conductance, or both.

Adolescent↗

The effects of the increase of arterial potassium upon the excitability of normal and dystrophic myotonic muscles in man.

Progressively increasing concentrations of potassium chloride were administered intra-arterially to patients affected with dystrophia myotonica (Steinert's disease) and to healthy volunteers before and after parenteral taurine treatment. Changes in the excitability of thenar eminence muscles were related to plasma potassium concentrations. A rise in the plasma potassium brought about a parallel increase of muscular excitability in normal individuals whilst in dystrophic myotonic patients it was associated with a two-phase phenomenon: the severity of myotonia first decreased and then, at higher plasma potassium levels, greatly worsened with the occurrence of spontaneous myotonic discharges. The administration of taurine, a membrane-stabilizing drug, considerably lowered the excitability of both normal and dystrophic myotonic muscles. The effects of potassium and taurine on muscular membrane conductance may explain the observed changes in muscular excitability.

Cell Membrane Permeability↗