Steroids in Duchenne muscular dystrophy--deflazacort trial

We conducted a double blind controlled trial in 28 Duchenne muscular dystrophy (DMD) patients with Deflazacort (DF), an oxazoline derivative of prednisolone which reduces its side-effects. Myometric muscle strength measurements, Scott Score and timed tests showed statistically significant improvement for the treated group (P less than 0.05). Side-effects after 9 months of treatment included mild cushingoid appearance in four patients (28%) and moderate in only one (7%), increased appetite in seven (50%), increased body hair in four (28%), irritability and hyperactivity in three (21%). Increased body weight was not prominent and was controlled with dietary measures. No patient had to be withdrawn from medication. More research and long-term follow-up are needed in order to establish the mechanism of improvement and the consequences of long-term steroid administration in DMD. In this regard DF appears as an alternative to prednisone preserving its benefits but with fewer side-effects.     

Motor activity and neurotransmitter release in the gastric fundus of streptozotocin-diabetic rats.

As deficiencies of the cholinergic and non-adrenergic non-cholinergic innervation of the gastrointestinal tract have been described in diabetic rats, we studied the simultaneous release of, and muscular response to, acetylcholine, vasoactive intestinal polypeptide and adenosine-5'-triphosphate in isolated preparations of gastric fundus from control and 8-week streptozotocin-treated diabetic rats. Muscular responses were measured in longitudinal muscle strips prepared from one half of the gastric fundus and release was studied in the other half. The contractile response to acetylcholine and electrical field stimulation was not different in control and diabetic rats. In the presence of atropine, and when tone was increased with prostaglandin F2 alpha, electrical field stimulation, vasoactive intestinal polypeptide and adenosine-5'-triphosphate induced relaxation with a similar response in control and diabetic rats. The basal release of acetylcholine, vasoactive intestinal polypeptide and adenosine-5'-triphosphate was not significantly different in control and diabetic rats. Electrical field stimulation significantly increased the release of the three substances and this increase was tetrodotoxin-sensitive. While the stimulation-induced increase of acetylcholine and vasoactive intestinal polypeptide was not different in control and in diabetic rats, the stimulation-induced release of adenosine-5'-triphosphate increased 3-fold in diabetic compared to control gastric fundus. Desensitization to alpha,beta-methylene adenosine-5'-triphosphate reduced the relaxant response to adenosine-5'-triphosphate and to electrical field stimulation, suggesting a role of adenosine-5'-triphosphate in non-adrenergic non-cholinergic neurotransmission of rat gastric fundus. The reduction of the non-adrenergic non-cholinergic relaxation by alpha,beta-methylene adenosine-5'-triphosphate was greater in diabetic tissues. This, with the increase in stimulation-induced adenosine-5'-triphosphate release, suggests that the purinergic component of the vagal non-adrenergic non-cholinergic response of the stomach may be increased in diabetics.     

Altered excitatory and inhibitory amino acid receptor binding in hippocampus of patients with temporal lobe epilepsy.

We examined binding to excitatory amino acid and inhibitory amino acid receptors in frozen hippocampal sections prepared from surgical specimens resected from 8 individuals with medically refractory temporal lobe epilepsy. The excitatory receptors studied included N-methyl-D-aspartate (NMDA), strychnine-insensitive glycine, phencyclidine, and quisqualate. The inhibitory receptors studied were gamma-aminobutyric acid type A (GABAA) and benzodiazepine. Excitatory and inhibitory amino acid receptor binding were differentially altered in the patients with temporal lobe epilepsy in comparison to 8 age-comparable autopsy control subjects, and changes in receptor binding were regionally selective in four areas. Binding to phencyclidine receptors associated with the NMDA channel was reduced by 35 to 70% in all regions in the hippocampi of the patients. In contrast, binding to the NMDA recognition site and its associated glycine modulatory site was elevated by 20 to 110% in the cornu ammonis (CA) 1 area and dentate gyrus of the hippocampus of the patients. Binding to these sites was unaffected in area CA4. Binding to the quisqualate-type excitatory amino acid receptor was unchanged in all regions except the stratum lacunosum moleculare CA1, where it was increased by 63%. GABAA and benzodiazepine receptor binding was reduced by 20 to 60% in CA1 and CA4, but unchanged in dentate gyrus. The data indicate that excitatory and inhibitory amino acid receptors are altered in the hippocampus of patients with temporal lobe epilepsy.     

Increased lymphocyte beta-adrenergic receptor density in progressive multiple sclerosis is specific for the CD8+, CD28- suppressor cell.

Beta-adrenergic receptor density on T cells from healthy humans is greatest on suppressor cells (CD8+, CD28-) and the effect of catecholamines, secreted by the sympathetic nervous system, predominates on this subset. The sympathetic skin response, a measure of sympathetic nervous system function, is absent in most patients with chronic progressive multiple sclerosis (MS). We measured beta-adrenergic receptor density on suppressor cells, cytotoxic cells, and monocytes from patients with chronic progressive MS and healthy control subjects. Control receptor density on suppressor cells was 2.8 +/- 0.3 fmol/10(6) cells versus a density of 5.1 +/- 0.7 fmol/10(6) cells for patients. Cytotoxic cell (CD8+, CD28+) receptor density was 1.4 +/- 0.4 fmol/10(6) cells in control subjects and 0.9 +/- 0.3 fmol/10(6) cells in the patients. Monocytes displayed beta-adrenergic receptor densities of 2.6 +/- 0.4 fmol/10(6) cells in normal individuals and 2.7 +/- 0.4 fmol/10(6) cells in the patient group. CD8 lymphocyte beta-adrenergic receptor densities in patients with relapsing-remitting and those with stable MS were not different from control values, yet were significantly less than the values for patients with chronic progressive MS. We find that mononuclear cells from healthy control subjects and patients with chronic progressive MS proliferate in response to 200 units/ml of recombinant human interleukin-2 (IL-2) similarly. However, IL-2 treatment increased beta-adrenergic receptor density on normal mononuclear cells, but failed to increase it on mononuclear cells from patients with chronic progressive MS.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pleuropulmonary disease associated with dopamine agonist therapy.

Artificial dopamine agonists are widely employed for the treatment of idiopathic parkinsonism. Pleuropulmonary disease has previously been reported to occur with the use of bromocriptine and mesulergine. We report similar adverse effects induced by the newer agonists lisuride and cabergoline. All these agents are tetracyclic ergot derivatives. This suggests a causal link between ergot-derived dopamine agonists and pleuropulmonary disease.     

Dynamics of functional interconnections between cerebral motor cortex neurons of cats under stimulation

In acute experiments on cats the activity of the motor cortex neurons was recorded. The dynamics of interneuronal connections at passive bending and electrostimulation of the limb contralateral to the place of recording was studied by methods of cross-correlation analysis of impulse trains. At passive bending a considerable decrease of the number of common inputs between neighbouring neurons (within 50-100 microns) and an increase in their number between remote (from 100 till 400 microns) cortical neurons. During electro-stimulation a certain increase in the number of direct inhibitory interactions between the neighbouring neurons was observed.     

Use of CT in epilepsy: does it matter how long you wait?

Computer tomography (CT) of the brain is of value for finding potentially correctable lesions in adult patients with new onset seizures. The value of CT is unknown, however, for finding such lesions in adult chronic epileptic patients without prior CT. We compared a group of 177 adult patients who had CT within a year from the onset of seizures to a group of 93 patients who had a history of seizures for more than a year before CT was performed. In the first group, 33 potentially correctable lesions (19%) were found including 17 tumors. The group with chronic epilepsy had 4 (4%) potentially correctable lesions: 3 arteriovenous malformations and 1 meningioma. It seems that CT is of value in discovering potentially removable lesions in chronic epileptic patients, but the likelihood is relatively small. The incidence of stable structural lesions seems to be similar in the two groups.     

Dissection of the extracranial vertebral artery: report of four cases and review of the literature.

Four cases of cervical vertebral artery (VA) dissection are reported. In three patients VA dissection was associated with neck trauma. All patients were young or middle-aged (range 27 to 49 years). In two there was a history of migraine. Pain preceded neurological symptoms from hours to six weeks. Three patients had neurological deficits including elements of the lateral medullary syndrome, and one experienced recurrent transient ischaemic attacks in the vertebrobasilar territory. Angiographic findings included irregular stenosis, occlusion and pseudoaneurysm; in two patients VA abnormalities were bilateral. All patients were treated with anticoagulants and improved. In a review of 28 cases with traumatic dissection and 29 cases with spontaneous dissection of the VA reported in the literature, distinct clinical and angiographic features emerge. Aetiology remains obscure in most cases of spontaneous dissection and management is still controversial.     

Screening recommendations for the elderly.

BACKGROUND. Studies have documented the potential contributions of preventive health care programs. Yet little is known about which screening tests should be included in public health programs for older persons. This study offers recommendations regarding these tests. METHODS. The recommendations come from synthesizing the findings of the US Preventive Services Task Force, the literature, and the consensus of experts in geriatrics, gerontology, and health policy research. The literature was evaluated to identify methodologically sound studies of the prevalence of selected disorders and benefits and availability of screening procedures for those disorders. Experts from various fields specializing in the care of the elderly formed panels to assist in evaluating the literature and providing further information from gerontological and public health perspectives. RESULTS. We recommend vision testing for refractive error; inspection of the skin surface for fungal infection and skin cancer, drug eruptions, and xerosis; a history for symptoms of xerosis; audiometric testing for presbycusis; surveys for hearing loss; otoscopic inspection for cerumen impaction; dental examination for caries; measurement of blood pressure for hypertension; and breast examination and mammography for cancer. CONCLUSIONS. Our study suggests that these screening procedures are useful for public health screening programs. More information is needed on the effects of screening services on the health and functioning of older persons.