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Biomedical subjects

J Olesen

Publications and source records attributed to J Olesen.

At least 127 records · Page 7Linked to original sources
PubMed1998

Zolmitriptan, a 5-HT1B/1D receptor agonist for the acute oral treatment of migraine: a multicentre, dose-range finding study.

Zolmitriptan is a selective 5-HT1B/1D receptor agonist for acute oral migraine therapy. This randomized, placebo-controlled, parallel-group study investigated the efficacy and tolerability of oral zolmitriptan (5, 10, 15 and 20 mg) in the treatment of single acute migraine attacks. Of 1181 patients randomized, 840 were evaluable for the primary efficacy analysis. Headache response rates (a reduction in headache intensity from severe or moderate at baseline to mild or no pain at 2 hours post-treatment) were similar across the zolmitriptan dose groups (66%, 71%, 69% and 77% for 5 mg, 10 mg, 15 mg and 20 mg, respectively) and were significantly higher than that for placebo (19%; all groups P < 0.001). A headache response was reported at 1 hour by 40-50% of zolmitriptan recipients (16% placebo). At 2 hours post dose, 39-47% of zolmitriptan-treated patients were pain-free, compared with 1% of placebo recipients. Headache recurrence occurred in 21-29% (upper 95% CI 37.1) of zolmitriptan-treated patients and in 65% (95% CI 38.3, 85.8) of placebo recipients. Zolmitriptan was well tolerated at each dose. The most commonly reported adverse events were asthenia, dizziness, paraesthesia and feelings of heaviness. Most adverse events were of mild or moderate intensity and were transient. The frequency of adverse events was dose-related. Although, zolmitriptan 5 mg exhibited the most favourable efficacy and tolerability profile, the dose response data suggest that lower doses would also offer significant efficacy. Copyright 1998 Lippincott Williams & Wilkins

Journal Article↗
PubMed1998

Activities in the Danish Year of the Brain 1997.

In this paper we report about the Danish Year of the Brain 1997 because it may serve as a model for other countries. It was possible in Denmark to organize a very large scale effort which has been well received by the general public and which has significantly improved the image of the neurological disciplines. The resources spent on nationwide initiatives in the Danish Year of the Brain are more than 2 million ECU in a country with 5 million inhabitants. In addition, however, considerable amounts were spent in each county of Denmark. Since all professionals have worked for free, innumerable hours of work have not been budgeted. In fact, the Danish Year of the Brain has been the largest privately organized health campaign ever held in Denmark and it has been so successful that the Danish Heart Association, which is old, well organized and extremely strong financially, has been worried about the shift of attention from the heart to the brain. Copyright 1998 Lippincott Williams & Wilkins

Journal Article↗
PubMed1998

Altered allelic distributions of the serotonin transporter gene in migraine without aura and migraine with aura.

Allelic variation of the human serotonin transporter gene (HSERT), a highly plausible candidate gene for susceptibility to migraine, was investigated in 266 individuals with migraine, including 173 having migraine without aura (MO), 94 having migraine with aura (MA), 18 with co-occurrence of MO and MA, plus 133 unaffected controls. The distribution of a polymorphism with different forms of a variable tandem number repeat (VNTR) in intron 2 were compared. The MO group had an over-representation of genotypes with two twelve repeat alleles (STin2.12) and a reduction of genotypes containing one ten repeat (STin2.10) compared to controls. The MA group showed a similar pattern, but also a trend towards an increase in genotypes containing the nine repeat allele of the VNTR (STin2.9). Genotypes containing this allele were found in 6.4% of the MA group compared to 2.3% of controls. The group with co-occurrence of MO and MA had a significantly different pattern of overall allele frequency distribution from controls, reflecting a reduction in genotypes containing the STin2.10 allele and a shift both to STin2.9 carriers and to STin2.12 homozygosity. These results support the view that susceptibility to MO and MA has a genetic component, that these disorders are distinct, and that genetic susceptibility may in some cases be associated with a locus at or near the serotonin transporter gene.

Adult↗
PubMed1998

Nitric oxide synthase inhibition: a new principle in the treatment of migraine attacks.

Glyceryl trinitrate, an exogenous nitric oxide (NO) donor, and histamine, which causes NO formation in vascular endothelium, have been shown to trigger migraine attacks. However, it remains uncertain whether NO is involved in the subsequent phase of migraine attacks. To answer this question we studied the effect of L-NGmethylarginine hydrochloride (546C88), a NO-synthase inhibitor, on spontaneous migraine attacks. In a double-blind study design, 18 patients with migraine without aura randomly received 546C88 (6 mg/kg) or placebo (5% dextrose) i.v. given over 15 min for a single migraine attack (546C88:placebo, 15:3). Furthermore, 11 placebo-treated patients from previous double-blind trials with almost identical design were added to the placebo group in the statistical evaluation. Two hours after the infusion, 10 of 15 L-NGmethylarginine hydrochloride-treated patients experienced headache relief compared to 2 of 14 placebo-treated patients (p = 0.01). Symptoms such as phono- and photophobia were also significantly improved. A similar trend for nausea was not significant. We conclude that NO may be involved in the pain mechanisms throughout the course of spontaneous migraine attacks.

Adolescent↗
PubMed1998

Measurement of muscle hardness: a methodological study.

The aim of the present study was to determine the intra- and interobserver variation during measurement of muscle hardness with a new instrument, a so-called hardness meter. In addition, we investigated the factors which may influence the recording of muscle hardness and whether the hardness differs within the same muscle. Hardness was measured at a standardized point on the trapezius muscle in 20 volunteers by 2 observers in random order and again by 1 of the observers after 30 min. Muscle hardness was then measured at 3 different locations on the trapezius muscle. In addition, the muscle hardness at the standard point was measured in 10 volunteers by both observers at 3 different speeds of the applied pressure. The intraobserver variation was 10% and the interobserver variation was 12% for recording of muscle hardness. There was no significant difference in hardness values from time to time within the same observer (p=0.12), while there was a significant difference in hardness measurements between observers (p=0.007). Muscle hardness differed significantly among the 3 anatomical locations (p=0.03). For both observers, there was a significant difference among hardness recordings obtained at 3 different speeds (p=0.01 and p=0.0001). In conclusion, we have shown that the hardness meter can measure muscle hardness reliably if the same observer is used throughout a study. The speed factor was a major source of variability In addition, we have demonstrated that muscle hardness differs within the same muscle. We suggest that the muscle hardness meter will be an important tool in future research of the mechanisms leading to myofascial pain.

Adult↗
PubMed1998

Muscular factors are of importance in tension-type headache.

Recent studies have indicated that muscular disorders may be of importance for the development of increased pain sensitivity in patients with chronic tension-type headache. The objective of the present study was to investigate this hypothesis by examining the pain perception in tension-type headache with and without muscular disorders defined as increased tenderness. We examined 28 patients with episodic tension-type headache, 28 patients with chronic tension-type headache, and 30 healthy controls. Pericranial myofascial tenderness was recorded with manual palpation, and pressure pain detection and tolerances in cephalic and extracephalic locations with an electronic pressure algometer. In addition, thermal pain sensitivity and electromyographic activity were recorded. The main result was significantly lower pressure pain detection thresholds and tolerances in all the examined locations in patients with chronic tension-type headache with a muscular disorder compared to those without a muscular disorder. There were no such differences in any of the examined locations when the two subgroups of patients with episodic tension-type headache were compared. Thermal pain sensitivity did not differ between patients with and without a muscular disorder, while electromyographic activity levels were significantly higher in patients with chronic tension-type headache with than in those without a muscular disorder. Our results strongly indicate that prolonged nociceptive stimuli from the pericranial myofascial tissue sensitize the central nervous system and, thereby, lead to an increased general pain sensitivity. Muscular factors may, therefore, be of major importance for the conversion of episodic into chronic tension-type headache. The present study complements the understanding of the important interactions between peripheral and central factors in tension-type headache and may lead to a better prevention and treatment of the most prevalent type of headache.

Adult↗
PubMed1998

No relation between cephalic venous dilatation and pain in migraine.

Evidence for the involvement of the cranial arterial system in migraine is plentiful, but it is unclear whether the cranial venous system may be involved in the mechanism of migraine pain. Venules are the preferentially involved vessels in the neurogenic inflammation animal model of migraine. The cranial and cerebral veins and sinuses are pain sensitive and receive sensory innervation from the trigeminal nerve. If the veins are involved in migraine pathogenesis, a venous dilatation would presumably be painful. The effect of a short lasting cranial venous dilatation, induced by applying pressure on the internal jugular veins (Queckenstedt's manoeuvre), was therefore compared with a placebo procedure, consisting of an equal pressure applied on to the lateral aspect of the neck. In each procedure pressure was applied for 10 seconds. The study used a single blind, randomised, cross over design, and 20 patients with an acute attack of migraine without aura participated. After each procedure, headache intensity was rated on a standardised five point scale. After Queckenstedt's manoeuvre 40% of the patients reported no change in headache intensity, 25% a worsening, and 35% an improvement of their headache. No significant difference between the headache intensity ratings during Queckenstedt's manoeuvre and the placebo manoeuvre was found (p=0.22). The findings make it unlikely that the cephalic venous system is of major importance in migraine pain mechanisms and, therefore, also less likely that neurogenic inflammation plays a significant part in humans during attacks of migraine without aura.

Adult↗
PubMed1998

Double-blind, randomized, placebo-controlled study of oral, high-dose methylprednisolone in attacks of MS.

OBJECTIVE: There is only limited evidence from adequately controlled clinical trials to support high-dose methylprednisolone therapy for attacks of multiple sclerosis (MS) and none supporting oral administration. We assessed the effect of oral high-dose methylprednisolone therapy in attacks of MS. METHODS: Twenty-five patients with an attack of MS lasting less than 4 weeks were randomized to placebo treatment. Twenty-six patients received oral methylprednisolone (500 mg once a day for 5 days with a 10-day tapering period). The patients received scores on the Scripps Neurological Rating Scale (NRS) and Kurtzke Expanded Disability Status Scale. The symptoms were scored on a visual analog scale (VAS) before treatment and after 1, 3, and 8 weeks of treatment. Primary efficacy measures were NRS and VAS scores in the first 3 weeks and changes in NRS score and answers to an efficacy questionnaire administered after 8 weeks of treatment. RESULTS: Changes in NRS scores among methylprednisolone- and placebo-treated patients differed significantly in the first 3 weeks and after 8 weeks (p = 0.005 and p = 0.0007). VAS scores the first 3 weeks and treatment efficacy after 8 weeks also favored a beneficial effect of methylprednisolone treatment (p = 0.02 and p = 0.05). After 1, 3, and 8 weeks, 4%, 24%, and 32% in the placebo group and 31%, 54%, and 65% in the methylprednisolone group had improved one point on the Expanded Disability Status Scale score (all p < 0.05). No serious adverse events were seen. CONCLUSION: Oral high-dose methylprednisolone is recommended for managing attacks of MS.

Administration, Oral↗
PubMed1998

Nitric oxide theory of migraine.

The molecular mechanisms of migraine pain have not yet been clarified. Neurogenic inflammation and a subsequent plasma extravasation in the dura mater have been suggested. However, monoamine and peptide neurotransmitters involved in neurogenic inflammation do not cause significant head pain. Based on our previous studies of headache induced by i.v.infusions of glyceryl trinitrate (exogenous nitric oxide donor) and histamine (which liberates nitric oxide from vascular endothelium), we suggest that nitric oxide (NO) is a more likely candidate molecule. The present review deals with the biology of this small messenger molecule and the scientific evidence suggesting a key role for this molecule in migraine headache. We hypothesise that the release of NO from either blood vessels, perivascular nerve endings, or brain tissue is a molecule trigger mechanism of spontaneous migraine pain. These novel observations dictate new approaches to the pharmacological treatment of migraine.

Brain↗
PubMed1997

Allelic variation in the serotonin 5-HT2C receptor gene and migraine.

The 5-HT2C (serotonin-2C) receptor has been implicated along with other components of the 5-HT system in the pathophysiology and pharmacotherapy of migraine. To investigate whether the 5-HT2C receptor gene contributes to the risk of migraine we performed an association study of allelic variation at codon 23 (Cys or Ser) of the gene in 242 migraineurs, including 73 with aura, and 129 controls. No differences nor trends in allele or genotype frequencies were seen in the migraineurs compared to the controls. Neither did the frequencies vary significantly in migraineurs with and without aura, or if men and women were analysed separately. In conjunction with an earlier negative linkage study, these data indicate that the 5-HT2C receptor gene does not contribute to the genetic predisposition to migraine.

Alleles↗
PubMed1997

Analysis of 31 families with an apparently autosomal-dominant transmission of migraine with aura in the nuclear family.

We analyzed 31 families selected for an apparently autosomal-dominant mode of inheritance of migraine with aura (MA) in the nuclear family. The nuclear families were expanded with first- and second-degree relatives. All interviews were made by physicians experienced in headache diagnoses. The criteria of the International Headache Society were used. The population relative risk among children in nuclear families was similar to the estimated population relative risk of MA assuming an autosomal-dominant mode of inheritance. The population relative risk tended to decrease among first-degree relatives outside nuclear families and further among second-degree relatives. Both first- and second-degree relatives outside the nuclear families had a statistically significant lower risk of MA than expected. Thus, autosomal-dominant inheritance with or without reduced penetrance was unlikely. Autosomal-recessive inheritance was unlikely because of the unequal sex distribution. Other modes of inheritance were considered as well. Mitochondrial and X-linked inheritance were excluded because of paternal transmission. The female preponderance was too low to explain sex-influenced inheritance. We conclude that MA most likely has a multifactorial inheritance even in high-risk families with MA.

Adolescent↗
PubMed1997

[Effects of nitrogen oxide donor glyceryl trinitrate on pressure pain threshold in humans].

The purpose of the present study was to examine the effect of the nitric oxide (NO) donor glyceryl trinitrate (GTN) on nociceptive thresholds in man. On two different study days twelve healthy subjects received a stair case infusion of GTN (0.015, 0.25, 1.0, 2.0 micrograms/kg/min 20 min each dose) or placebo in a randomized double-blind cross-over design. Before the infusion and after 15 min of infusion on each dose, pressure pain detection- and tolerance thresholds were determined by pressure algometry in three different anatomic regions (finger, a temporal region with interposed myofascial tissue and a temporal region without interposed myofascial tissue). Relative to placebo the three higher GTN doses induced a decrease in both detection- and tolerance-thresholds in the temporal region with interposed myofascial tissue. No such changes were observed in the two other stimulated regions. These results could reflect central facilitation of nociception by NO. However, convergence of nociceptive input from pericranial myofascial tissue and from cephalic blood vessels dilated by NO may provide a more likely explanation.

Adult↗
PubMed1997

[Decreased pain threshold and tolerance in patients with chronic tension headache].

Nociceptive processing was studied in 40 patients with chronic tension-type headache and in 40 healthy controls. We found that pericranial tenderness recorded by manual palpation was considerably higher in patients than in controls (p < or = 0.0002). Pressure pain detection and tolerance thresholds recorded in the finger, by means of a pressure algometer, were significantly lower in patients than in controls (p < or = 0.0009), and a non-significant similar trend was observed in the temple (p < or = 0.12). Detection and tolerance thresholds were decreased to a similar degree in patients compared with controls, and pain thresholds recorded in the finger and in the temple were highly correlated (r = 0.84, p < 0.0001). The electrical pain threshold at the labial commissure, by means of an electrical stimulator, was significantly decreased in patients compared with controls (p = 0.03). All of the examined pain thresholds were significantly correlated to the pericranial tenderness recorded by palpation (r = -0.35 to -0.53, p < or = 0.03). We conclude that the present finding of a general hypersensitivity to pain stimuli in chronic tension-type headache indicates that central factors play an important role in the pathogenesis of this disorder.

Adolescent↗