Search PubMed⌕ Search

Biomedical subjects

E Hokkanen

Publications and source records attributed to E Hokkanen.

At least 19 recordsLinked to original sources

Multiple-dose pharmacokinetic study with a slow-release carbamazepine preparation.

The pharmacokinetics, clinical efficacy and side effects of carbamazepine (CBZ) in the steady-state condition were studied using a slow-release preparation (SR), Neurotol Slow, and a conventional preparation (C), Tegretol. Eighteen adult epileptic patients under CBZ therapy were evaluated in this single-blind, randomized cross-over study. The previous daily CBZ dose was kept unchanged and divided into 2 daily doses during two 2 week study periods. At the end of each period blood samples were drawn at frequent intervals for 12 h after the administration of the morning CBZ dose. Serum concentrations of unchanged CBZ and its main metabolite, carbamazepine-10,11-epoxide (CBZE), were determined by HPLC. Peak concentrations of CBZ and CBZE were significantly lower, and the time-lapse before CBZ reached its peak was significantly longer during SR treatment. The fluctuations in serum CBZ and CBZE were significantly lower during SR treatment. There was no significant difference in bioavailability between the 2 preparations. The number of epileptic seizures was 31 during SR and 57 during C treatment. Side effects were more common during C treatment. The occurrence of dizziness was significantly lower with SR treatment than with C treatment. We conclude that greater stability in serum CBZ and CBZE concentrations can be obtained by using an SR of CBZ, without reducing the bioavailability of the drug.

Adult↗

Efficacy of nimodipine in comparison with pizotifen in the prophylaxis of migraine.

The efficacy of nimodipine in comparison with that of pizotifen was assessed in the prophylaxis of migraine in a double-blind cross-over study, in which a double-dummy technique was also utilized. The study was carried out on 43 migraine patients, of whom 15 had classic and 28 had common migraine. A 4-week run-in placebo period preceded the drug treatments, the drug treatments lasted 12 weeks, and there was a washout placebo period of 4 weeks between nimodipine and pizotifen treatments. The dosages used were 40 mg three times daily for nimodipine and 0.5 mg three times daily for pizotifen. Both nimodipine and pizotifen proved to be better than placebo, the number of migraine attacks showing a significant reduction. There was no difference between nimodipine and pizotifen in antimigrainous efficacy, but there were fewer side effects during the nimodipine period. The results suggest that nimodipine is an effective drug for the prophylaxis of migraine, with few side effects and therapeutic efficacy equal to that of pizotifen.

Adolescent↗

Efficacy of nimodipine in the prophylaxis of migraine.

The efficacy of nimodipine in the prophylaxis of migraine was assessed in a double-blind, placebo-controlled, cross-over study carried out on 33 patients, 20 of whom suffered from classic and 13 from common migraine. Four patients dropped out, but not as a result of the side effects of the drug. The duration of drug treatment was 8 weeks. The dosage used was 30 mg four times daily. Nimodipine proved to be better than placebo, the number of migraine attacks and severity of headache showing a significant reduction. The drug was well tolerated and no marked side effects were noted. The results suggest that nimodipine is a useful new prophylactic drug for migraine, but further studies are needed before its final value can be evaluated.

Adult↗

Relevance of prostaglandins in migraine.

Prostaglandins (PG), particularly PGE, may be linked to the pathophysiology of migraine in several important ways. PGE1 may "simulate" a migraine attack in healthy volunteers. PGE may be elevated in patients with migraine. In animal experiments and in human infusions, PGEs cause vasodilation and hyperalgesia, both typical reactions of inflammation. The view that vascular headache is an "inflammatory reaction" allows the best concept concerning the local role of PGs and the effectiveness of PG-inhibitors in the treatment of migraine. The local role of PGs may provide a common denominator in several hormonal, neural and other influences on vessels. The common triggers of a migraine attack like menstruation, alcohol and stress influence the PG-system and even the dietary reactions, hormonal influences, sleep and reserpine have some connections with the PG-system. A local role for PGs does not diminish the importance of other pathophysiological mechanisms operating during an attack. On the contrary, PGs may fill in gaps in our understanding of how the overt pain of attacks is produced.

Animals↗

Ergotamine abuse: results of ergotamine discontinuation, with special reference to the plasma concentrations.

Twenty-three patients suffering from continuous headache linked with habitual daily use of ergotamine tartrate were studied. Their headaches were classified clinically, and possible side effects of ergotamine medication, plasma levels of ergotamine, and occurrence of withdrawal symptoms after discontinuation of drug abuse were recorded. Seventeen of the patients were clinically diagnosed as suffering from "ergotamine headache", and seven of them complained of coldness in the extremities. Plasma ergotamine levels were measured by using a radioimmunoassay. In almost half of the patients the 1 h plasma levels after the daily dose were below the detection limit of the procedure (0.12 ng/ml). The duration and severity of the withdrawal symptoms did not correlate with the doses and plasma levels of ergotamine. In only 4 of the 21 patients who were followed up for 3 to 6 months did headache symptoms not improve after ergotamine withdrawal. The results indicate that even small (0.5-1.0 mg/day) doses of ergotamine tartrate taken regularly may cause continuous headache symptoms and withdrawal symptoms after discontinuation.

Adult↗

Cerebrospinal fluid protein findings in cervical syndromes classified by myelography, and in multiple sclerosis.

Determinations of cerebrospinal fluid (CSF) albumin, IgG, albumin blood brain barrier (BBB) permeability and local IgG synthesis indexes in CNS were carried out on 85 patients with various neck, shoulder and upper extremity pain syndromes. CSF was obtained by lumbar puncture in 29, and by lateral neck puncture in 56 of the patients. The patients were classified into 3 different groups according to varying severity of degenerative changes, or cavitation verified by myelography. CSF protein patterns in these patients were compared with lumbar CSF findings in 18 patients with multiple sclerosis. CSF protein changes in patients with abnormal myelographic findings were slight. Protein values were clearly more abnormal in lumbar CSF than in cervical CSF, probably due to a retardation of the CSF flow. Only 3 of 62 patients with a narrowing of the cervical spinal canal had pathological values for IgG synthesis or BBB permeability indexes. On the other hand 14 of 18 patients with multiple sclerosis had abnormal, high values for the IgG index. Thus the present results suggest that investigation of the CSF protein pattern has value in differential diagnosis between patients with multiple sclerosis and degenerative diseases of the cervical spine.

Adolescent↗

Serial measurements of quantitative EEG and cerebral blood flow and circulation time after brain infarction.

The quantitative EEG (QEEG), regional cerebral blood flow (rCBF) and circulation time of 17 patients were examined semisimultaneously thrice during the first 3 months after a cerebral supratentorial infarction. The EEG was quantified according to normalized slope descriptor technique in nine patients and by means of a combined period and amplitude analysis in eight patients. Intravenously injected isotopes 133Xenon and 99TcmO4 were used for blood flow and circulation time measurements. The QEEG-values improved during the whole follow-up period. Cerebral blood flow stayed low for all 3 months and did not alter during this period, while initially prolonged circulation time to some extent improved within 2 weeks remaining, however, prolonged even thereafter. A tendency for a positive correlation between QEEG and rCBF values in the infarcted hemisphere could be seen.

Adult↗

Evaluation of cerebral infarctions of the carotid area by an intravenous 133Xenon and 99mTechnetium method.

Quantitative determinations of regional cerebral blood flow (rCBFf, rCBFm) and volume (rCBV), transfer time (rCTT) and fast compartmental weight (Wf) were performed in 34 patients with infarctions of the carotid area by a 133Xe and 99mTc intravenous injection method. The results were compared with clinical signs and electroencephalographic (EEG) findings. A significant difference was found between the lesion side and the control side in all the parameters except rCBV. This difference increased with the severity of the infarction and age of the patients. The difference between the two sides was especially great in the patients with totally occluded internal carotid artery. A slight diaschisis could be observed in the present infarction group. An almost significant reduction on the "normal side" was seen in Wf. In order to assess the reciprocal influence of all the different blood flow parameters, the difference index (DI): Formula: (see text) was calculated, where delta i = the difference between the two sides in one parameter expressed in percent. This proved to be abnormal in 80% of the patients. The atraumatic isotope technique employed offers a good opportunity for the quantitative evaluation of hemodynamics in cerebral infarction and serves as an aid in the diagnosis of infarction.

Adult↗

Systemic availability of ergotamine tartrate in continuous medication.

There seems to be great individual differences in the bioavailability of ergotamine in continuous use. The great tolerance to ergotamine in some patients using the drug on a daily basis, even in high doses, may be due to the low-bioavailability of ergotamine in these subjects. This may also explain the infrequency of serious complications among migraine patients.

Adult↗

Systemic availability of ergotamine tartrate in healthy subjects after single and repeated oral doses.

The studies presented indicate that ergotamine tartrate taken orally in single or repeated 2 mg doses is biologically available in most of the subjects examined. The peak plasma concentration of the drug in the ng/ml range is attained at 1-2 hours. It seems probable that there is a second rise in the plasma concentrations of the drug, possibly indicating an accumulation of ergotamine or some of its immunoreactive metabolites, and this needs further evaluation.

Administration, Oral↗

Systemic availability of ergotamine tartrate after oral, rectal and intramuscular administration.

Plasma ergotamine levels were measured in 33 volunteers (subgroups 11, 12 and 10) after a single dose of ergotamine administered by various routes. Ergotamine tartrate was given in doses normally used in the treatment of acute migraine--2.0 mg orally, 2.0 mg combined with 100 mg caffeine rectally and 0.5 mg i.m. Plasma ergotamine concentrations were determined by radioimmunoassay. The highest and longest lasting levels were found after i.m. administration, the peak concentration being 1.94 +/- 0.34 (SEM) ng/ml at 1/2 h. The corresponding maximum concentrations after oral and rectal administration were 0.36 +/- 0.08 ng/ml at 2 h and 0.42 +/- 0.09 ng/ml at 1 h. In most of the subjects the plasma ergotamine level began to rise again at 24 to 48 h. The cause of the elevation is not known but it might favour possible accumulation of the drug. Absorption from suppositories was at least as good as after oral administration and the former route may therefore be advantageous for migraine patients in whom nausea and vomiting during an attack may prevent efficient oral medication.

Administration, Oral↗

Cerebrospinal fluid protein findings in various lower back pain syndromes.

Cerebrospinal fluid (CSF) total protein, albumin and IgG concentrations were measured in 53 patients with lower back pain syndromes. In the majority of the patients (81 %) the protein values were within normal ranges, a finding contrary to previous studies. In six of 28 patients with acute lumbar disc prolapse and in two of four cases with spinal stenosis, a clearly abnormal protein pattern was observed, while patients who had been earlier operated on for disc prolapse showed normal values. The calculated permeability indexes suggest that the elevation of various proteins is linked with increased permeability across the blood-brain barrier and that the local immunoglobulin synthesis in CNS is lacking. In only one of the cases with an abnormal CSF protein pattern could no evidence of the cause of the pathological finding be observed in subsequent examinations.

Adult↗