OBJECTIVE: To determine the effectiveness and tolerability of intravenous valproate for the acute treatment of migraine headache with or without aura (International Headache Society diagnostic criteria 1.1 and 1.2) compared with intramuscular metoclopramide 10 mg followed 10 minutes later by intramuscular dihydroergotamine 1 mg. BACKGROUND: Divalproex sodium is approved for prophylaxis of migraine headache. We studied the possible effectiveness of intravenous sodium valproate for the treatment of acute migraine headache. Valproate offers a treatment option for patients with migraine who recently have used a triptan or dihydroergotamine, theoretically avoiding the risk of drug interactions or cardiovascular complications. DESIGN/METHODS: In an open-label randomization, patients with an established diagnosis of migraine with or without aura were administered either intravenous valproate or intramuscular dihydroergotamine with metoclopramide to treat moderate-to-severe migraine headache of 24 to 96 hours' duration. Forty patients alternately received either 500 mg intravenous valproate or 10 mg metoclopramide intramuscularly followed by 1 mg dihydro- ergotamine. Patients rated severity of headache and the presence or absence of nausea, photophobia, or phonophobia at baseline, and at 1, 2, 4, and 24 hours. RESULTS: With intravenous valproate, 50% of patients reported headache improvement from moderate or severe to none or mild at 1 hour following treatment, 60% reported such improvement at 2 hours, 60% at 4 hours, and 60% at 24 hours. Corresponding improvement rates for dihydroergotamine were 45% at 1 hour, 50% at 2 hours, 60% at 4 hours, and 90% at 24 hours. Intravenous valproate and intramuscular dihydroergotamine provided similar relief from associated migrainous symptoms (nausea, photophobia, and phonophobia) during the first 4 hours following treatment. While none of the patients who received intravenous valproate experienced drug-related side effects during treatment, 15% of patients who took dihydroergotamine experienced one or more episodes of nausea and diarrhea during the first 4 hours of treatment. CONCLUSIONS: Intravenous valproate is similar in effectiveness to dihydroergotamine/metoclopramide as abortive therapy for prolonged moderate-to-severe acute migraine headache. Although the results were not statistically significant (P =.3635), intravenous valproate appears to offer a safe, effective, and well-tolerated treatment for patients with acute migraine. Relative to dihydroergotamine/metoclopramide, however, headache relief was not as likely to be sustained at 24 hours as with intravenous valproate.

Acute Disease↗

PubMedDate not supplied

BRL 34915, a novel antihypertensive agent: comparison of effects on blood pressure and other haemodynamic parameters with those of nifedipine in animal models.

The effects of BRL 34915, (+/-) 6-cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidyl)-2H-b enzo [b]-pyran-3-ol, on blood pressure and other haemodynamic parameters in animals have been investigated in comparison with those of nifedipine. In conscious spontaneously hypertensive rats and renal hypertensive cats and dogs the oral doses of BRL 34915 lowering blood pressure are 10 to 30 times lower than those of nifedipine. Tachycardia evoked by BRL 34915 tends to be less than that produced by nifedipine in the cat and of similar magnitude in the dog. The antihypertensive response to BRL 34915 in these models is reproducible on repeat once daily dosing without rebound hypertension on cessation of dosing. In studies using electromagnetic flow probes to measure regional blood flow in anaesthetised cats the intravenous administration of BRL 34915, unlike that of nifedipine, markedly increases renal blood flow yet BRL 34915 lacks the marked effect of nifedipine on femoral blood flow. BRL 34915, a compound structurally unrelated to existing cardiovascular drugs, is a potent new antihypertensive agent having an interesting profile of activity that renders this compound of clinical interest.

Animals↗

PubMedDate not supplied

Nerve cell loss in the progressive encephalopathy induced by aluminum powder. A morphologic and semiquantitative study of the Purkinje cells.

The injection of aluminum powder into the cerebrospinal fluid induces a slowly progressing encephalomyelopathy with cerebellar atrophy. We have studied the changes in the cerebellar cortex in order to establish whether Purkinje cell loss takes place. The rabbits were killed by perfusion with paraformaldehyde and glutaraldehyde at intervals from 3 to 85 days after injection of aluminum. Changes were observed in all animals killed between 12 and 85 days after the injection. Neurofibrillary degeneration with 10 nm neurofilaments was observed in the perikaryon of Purkinje cells. The neurofibrillary tangles extended into the proximal part of the dendrites and of the axons. A time-related deterioration of the Purkinje cells was observed. These cells appeared atrophic with eccentric and shrunken nuclei and with dark cytoplasm. By electron microscopy debris of Purkinje cell perikarya, dendrites and axons were found. The semiquantitative analysis revealed a time-related loss of Purkinje cells. Atrophy of the molecular and granule cell layers was observed. A marked proliferation of glial cells contrasted with the severe neuronal losses. Such findings may be relevant to several human diseases in which the central nervous system is exposed to aluminum over long periods of time.

Aluminum↗

PubMedDate not supplied

Ventral root axonopathy and its relation to the neurofibrillary degeneration of lower motor neurons in aluminum-induced encephalomyelopathy.

The injection of metallic aluminum (Al) into the cerebrospinal fluid of adult rabbits induces neurofibrillary degeneration of lower motor neurons. We studied the ventral roots and the corresponding motor neurons of Al-treated animals to clarify the modality and extent of reaction of the axon in relation to the severity of perikaryonal involvement. Moreover, the involvement of dorsal root ganglion cells was compared to that of lower motor neurons. Rabbits received 0.15 ml of a 1% Al slurry intracisternally and were perfused through the heart with aldehydes at 14-62 days after injection. Spinal cords and roots were embedded in Epon and examined morphologically and by morphometric techniques. An axonopathy was observed in the ventral roots, characterized by neurofilamentous axonal swellings and myelin attenuation in several size classes of axons. Results obtained from axons traced in serial sections indicate that there may be a unifocal or a multifocal axonopathy. Dorsal root ganglion cells showed milder changes by comparison with motor neurons and their axons in the ventral roots. The most severe axonopathy was associated both with an incidence of 66-81% of motor neurons showing neurofibrillary degeneration and with a rapidly progressing motor weakness. These findings are related in the discussion section to the pathological expression of human neurological disorders in which the lower motor neurons are selective targets.

Aluminum↗

PubMedDate not supplied

Elevated plasma hydroxyproline. A possible risk factor associated with connective tissue injuries during overuse.

Basal plasma hydroxyproline was measured in 104 male Navy Seal candidates 1 week into their intense physical training program, which lasted 7 weeks, and correlated to the incidence of connective tissue injuries incurred later in the training program. Eleven subjects (10.6%) were diagnosed as having connective tissue injuries. Those subjects with connective tissue injuries had a significantly higher (P less than 0.05) mean plasma hydroxyproline value (4.02 micrograms/ml) than subjects without injury (3.10 micrograms/ml). The majority of graduates (75%) had plasma hydroxyproline values less than 3.3 micrograms/ml. These graduates represented the strongest and most enduring injury-free subjects. Of the subject pool who incurred connective tissue injuries, only 27% had plasma hydroxyproline values less than 3.3 micrograms/ml. The majority of the injured subjects (73%) had plasma hydroxyproline values greater than or equal to 3.3 micrograms/ml. In conclusion, there is a relationship between initial training basal plasma hydroxyproline levels and connective tissue injuries later incurred in an intense physical training program. These data suggest that elevated plasma hydroxyproline levels may represent a risk factor associated with connective tissue injuries.

Adolescent↗

PubMedDate not supplied

Gerontological nursing: forging new paths.

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Aged↗

PubMedDate not supplied

Industry involvement in Australian agrobiotechnology: the views of scientists.

In the October 1993 edition of Australasian Biotechnology a special feature on 'the biotechnology debate' raised issues such as public acceptance of biotechnological products, the ethical issues surrounding the new technology and commercialisation. In regard to the latter, it was suggested that Australian scientists no longer believe there are major (or negative) consequences concerning the involvement of private firms in public research. This paper reports on an Australia-wide survey of several hundred biotechnologists who were involved in agriculturally-related research. Findings indicate that while those surveyed believe that commercial linkages are necessary for the continued development of the industry, they remain concerned that such linkages are altering the trajectory of science.

Agriculture↗

PubMedDate not supplied

PGE2 in the perinatal brain: local synthesis and transfer across the blood brain barrier.

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Animals↗