Biomedical subjects

J Olesen

Publications and source records attributed to J Olesen.

At least 19 recordsLinked to original sources

PubMed2000

Plasma levels of calcitonin gene-related peptide in chronic tension-type headache.

BACKGROUND: Calcitonin gene-related peptide (CGRP) is involved in the pathophysiology of migraine and cluster headache. Whether CGRP has any role in chronic tension-type headache is unknown. OBJECTIVES: To compare interictal plasma levels of CGRP between patients with chronic tension-type headache and healthy control subjects, to investigate plasma CGRP in relation to headache state, and to compare plasma CGRP between the peripheral and the cranial circulation. METHODS: Blood from the antecubital vein was drawn from 30 patients with chronic tension-type headache and 34 healthy control subjects. In addition, blood samples from the consecutive first 15 patients and from the consecutive first 20 healthy control subjects were also collected from the external jugular vein. RESULTS: CGRP levels measured in the peripheral circulation in patients on days without headache, 63+/-5 pmol/L, tended to be higher than CGRP levels in control subjects, 53+/-3 pmol/L (p = 0.06). In patients, no differences were found between CGRP levels assessed ictally and interictally in either the cranial (p = 0.91) or the peripheral (p = 0.62) circulation. Plasma CGRP level was higher in the external jugular vein than in the antecubital vein on days without headache (p = 0.03) but not on days with headache (p = 0.82). In control subjects, CGRP levels in the cranial circulation did not differ from CGRP levels in the peripheral circulation (p = 0.92). Exploratory analyses showed that 8 patients whose usual headache quality was throbbing had a higher interictal plasma CGRP level than control subjects (p = 0.002), whereas plasma CGRP level was normal in 22 patients with pressing headaches (p = 0.36). CONCLUSIONS: Plasma levels of CGRP are normal in patients with chronic tension-type headache and are unrelated to headache state. Interictal plasma CGRP was increased in patients with a pulsating pain quality. Because the authors have previously shown a similar increase of interictal CGRP levels in migraine, this study suggests that headaches with symptoms that fulfill International Headache Society criteria for tension-type headache may be pathophysiologically related to migraine, if the headache has a pulsating quality.

Adult↗

PubMed2000

Eletriptan in acute migraine: a double-blind, placebo-controlled comparison to sumatriptan. Eletriptan Steering Committee.

OBJECTIVE: To compare the efficacy, safety, and tolerability of oral eletriptan (20 mg, 40 mg, and 80 mg) with that of oral sumatriptan (100 mg) and placebo for the acute treatment of migraine. BACKGROUND: Eletriptan is a potent and selective agonist at human recombinant 5HT1B/1D receptors, with efficacy in animal models that predict antimigraine activity. In healthy volunteers, the pharmacokinetics of eletriptan are characterized by linear and rapid oral absorption. METHODS: Randomized, double-blind, parallel-group study conducted in 857 outpatients with a diagnosis of migraine according to the International Headache Society (IHS) criteria. Of these, 692 took study medication for one acute migraine attack and provided on-drug efficacy data. Subjects received either placebo, 100 mg of sumatriptan or 20 mg, 40 mg, or 80 mg of eletriptan for the treatment of an acute migraine attack. The primary endpoint was the percentage of patients with a headache response (improvement in pain intensity from moderate or severe to mild or none) at 2 hours after treatment. RESULTS: At the primary endpoint (2 hours after dosing), headache response rates were 24% (30/126) for placebo; 55% (63/115) for sumatriptan, 100 mg; 54% (70/129) for eletriptan, 20 mg; 65% (76/117) for eletriptan, 40 mg; and 77% (91/118) for eletriptan, 80 mg. There was a difference compared with placebo (p<0.001) for all doses of eletriptan, and at 2 hours there was a difference between sumatriptan, 100 mg, and eletriptan, 80 mg (p<0.001). Headache-free rates at 2 hours were superior to placebo (6%; p<0.001) for both the 80-mg dose of eletriptan (37%) and the 40-mg dose (29%), with the 80-mg dose also being superior to 100 mg of sumatriptan (23%; p<0.05). Eletriptan and sumatriptan were well tolerated, and the majority of adverse events were mild or moderate in intensity and transient. CONCLUSION: In this placebo-controlled trial, eletriptan, at selected doses, demonstrated superior efficacy, onset of action and patient acceptability in the acute treatment of migraine when compared with oral sumatriptan and placebo.

Acute Disease↗

PubMed2000

[The significance of genetic and environmental factors for migraine with aura. A genetic epidemiologic study of Danish twins].

We studied the genetic and environmental influence on migraine with aura (MA) by analysing a twin population. The twin sample consisted of 2,026 monozygotic (MZ) pairs and 3,334 same-gender dizygotic (DZ) pairs recruited from the population-based Danish Twin Register. A total of 211 pairs were identified, of whom 77 were MZ and 134 were DZ. The pairwise concordance rate was significantly higher in MZ-than in DZ-pairs, i.e. 34% and 12%, respectively, emphasizing the importance of genetic factors in MA. However, environmental factors are also important, as the pair wise concordance rate was less than 100% in MZ-pairs. Similarly, the recurrence risk of MA was 50% in MZ- and 21% in DZ-pairs which was a significant difference. In non-twin siblings, the recurrence risk of MA is 27%, which is similar to the recurrence risk in DZ-pairs. This indicates that MA is not developed due to specific environmental factors shared by the twins.

Adult↗

PubMed2000

[Inhibition of nitric oxide synthase has an analgesic effect in chronic pain].

The efficacy of the inhibitor of nitric oxide synthase, NG-monomethyl-L-arginine hydrochloride (L-NMMA), was tested in 16 patients with chronic tension-type chronic headache. The study was designed as a randomized double-blind, crossover trial. Patients were assigned intravenous infusion of 6 mg/kg L-NMMA or placebo on two days separated by at least one week in a randomized order. Headache intensity was measured on a 100 mm visual analogue scale at baseline and at 30 min, 60 min, and 120 min after start of treatment. L-NMMA reduced pain intensity significantly more than placebo: 120 min after start of treatment, the mean pain score was decreased from 49 to 33 with L-NMMA and from 44 to 40 with placebo (p = 0.01). The present study demonstrates that inhibition of NOS has an analgesic effect in chronic tension-type headache.

Adult↗

PubMed2000

Evidence for increased plasma levels of calcitonin gene-related peptide in migraine outside of attacks.

Although calcitonin gene-related peptide (CGRP) has been shown to be elevated in jugular venous blood of adult migraineurs during acute migraine attacks, it remains unknown whether CGRP is increased outside of attacks in jugular or cubital venous blood. The aim of the present study was to compare interictal plasma levels of CGRP in adult migraine patients and in healthy controls. Twenty patients with a diagnosis of migraine with or without aura and 20 healthy controls were included. In blood from the cubital vein, CGRP levels were significantly higher in patients (75+/-8 pmol/l (mean+/-SEM)) than in controls (49+/-3 pmol/l) (P=0.005). The subgroup of patients suffering exclusively from migraine without aura (n=14) also had significantly higher levels of CGRP (82+/-10 pmol/l) than controls (n=20; 49+/-3 pmol/l) (P=0.001). The findings could not be explained by confounding factors such as age, sex or use of contraceptive pills. We therefore conclude that CGRP is increased in cubital venous blood of migraineurs outside of attack. It is hypothesized that this finding may reflect a long-lasting or permanent abnormal neurogenic vascular control in patients with migraine.

Adult↗

PubMed2000

In vivo studies of peritendinous tissue in exercise.

Soft tissue injury of tendons represents a major problem within sports medicine. Although several animal and cell culture studies have addressed this, human experiments have been limited in their ability to follow changes in specific tissue directly in response to interventions. Recently, methods have allowed for in vivo determination of tissue concentrations and release rates of substances involved in metabolism, inflammation and collagen synthesis, together with the measurement of tissue blood flow and oxygenation in the peritendinous region around the Achilles tendon in humans during exercise. It can be demonstrated that this region experiences an increase in blood flow during both static and dynamic exercise, and that exercise causes increased metabolic activity, accumulation of inflammatory mediators (prostaglandins) and increased formation of collagen type I in response to acute exercise. This coincides with a surprisingly marked drop in tissue pressure during contraction. With regards to both circulation, metabolism and collagen formation, peritendinous tissue represents a dynamic, responsive region that adapts markedly to acute muscular activity.

Achilles Tendon↗

PubMed2000

Glyceryl trinitrate induced headache in migraineurs - relation to attack frequency.

Glyceryl trinitrate, a prodrug of nitric oxide, induces a mild to moderate headache in healthy subjects, whilst migraineurs develop a more severe headache, resembling spontaneous migraine attacks. In order to investigate whether this increased nitric oxide sensitivity depends upon the frequency of spontaneously occurring migraine attacks, intravenous infusion of glyceryl trinitrate (0.5 microg/kg/min) was given to 15 migraine patients with rare attacks (</=4 attacks/year) of migraine without aura. Fourteen age-matched migraine patients with frequent attacks of migraine without aura (>/=12 attacks/year) and 14 healthy subjects served as controls. No significant difference between the migraine groups for any of several parameters was detected, although the trend was always towards more headaches in frequent migraineurs. Both migraineurs with frequent and rare attacks experienced a headache that was significantly more severe, longer lasting, and fulfilled the diagnostic criteria for migraine without aura more often, compared to the healthy subjects (P = 0.0001). Conclusively, supersensitivity to glyceryl trinitrate in migraineurs seems to be related to a basic - probably genetically determined - pathophysiological mechanism involving nitric oxide, and not to the environmental influences, which to a large extent determine the expression of migraine.

Adult↗

PubMed2000

Comparison of the efficacy of zolmitriptan and sumatriptan: issues in migraine trial design.

In this international, multicentre, double-blind, placebo-controlled, single attack study, 'triptan naive' migraine patients were randomized in an 8:8:1 ratio to receive zolmitriptan 5 mg, sumatriptan 100 mg or placebo. The all-treated analysis included 1058 patients who took study medication. The primary endpoint, complete headache response, was reported by 39%, 38% and 32% of patients treated with zolmitriptan, sumatriptan and placebo, respectively, with no significant difference between treatment groups. In patients with moderate headache at baseline, complete response was significantly greater following zolmitriptan than after placebo (48% vs. 27%; P=0.01); there was no significant difference between sumatriptan and placebo groups (40% vs. 27%). In patients with severe baseline headache (where a greater reduction in headache intensity is required for a headache response), there was no significant difference between any groups in complete headache response rates. For secondary endpoints, active treatment groups were significantly superior to placebo for: 1-, 2- and 4-h headache response (e.g. 2-h headache response rates: zolmitriptan 59%; sumatriptan 61%; placebo 44%; P < 0.01 vs. placebo); pain-free response rates at 2 and 4 h; alleviation of nausea and vomiting; use of escape medication and restoration of normal activity. The incidence of adverse events was similar between zolmitriptan and sumatriptan groups but was slightly lower in the placebo group. The lack of difference between active treatments and placebo for complete response probably reflects the high placebo response obtained, which is probably a result of deficiencies in trial design. For example, the randomization ratio may result in high expectation of active treatment. Thus, while ethically patient exposure to placebo should be minimized, this must be balanced against the scientific rationale underpinning study design.

Adolescent↗

PubMed2000

Headache characteristics during the development of tolerance to nitrates: pathophysiological implications.

Recent studies suggest that nitric oxide (NO) plays an important role in nitrate-induced headache and in spontaneous migraine attacks. Organic nitrates act as prodrugs for NO and headache is a predominant adverse effect of nitrates but often disappears during continuous treatment. Insight into tolerance to headache could lead to insight into vascular headache mechanisms in general. The specific aim of the present study was therefore to characterize the headache and accompanying symptoms during continuous nitrate administration until a state of tolerance to headache had developed. 5-isosorbide-mononitrate (5-ISMN) 30 mg three times daily was administered orally for 7 days in 11 healthy subjects in a double-blind, randomized placebo controlled cross-over design. Wash-out between periods was 14 days or more. Haemodynamic data from the present study were compared to the observed changes of headache over time. Headache during 5-ISMN was longer lasting and more severe compared to placebo (P<0.004). In 10 subjects the headache fulfilled the pain sub-criteria for migraine and in five subjects all diagnostic criteria for migraine without aura were fulfilled. Conversely, 20 min of intravenous infusion of glyceryl trinitrate caused a milder headache and no migraine. The present results therefore suggest that NO may elicit a migraine attack in many healthy subjects if a high enough dose is given for several hours. A close temporal association between the disappearance of headache and the attenuation of the 5-ISMN induced dilatation of the superficial temporal artery was observed. In contrast, tolerance in the middle cerebral artery already appeared after 24 h, which was earlier than the development of tolerance to headache. If vasodilatation is the cause of headache the results point to extracerebral arteries. However, cytotoxic and pain modulating central nervous system effects of NO, the time courses of which are unknown, may also play a role, involving both intra- and extracranial arteries.

Administration, Oral↗

PubMed2000

Induction of nitrate tolerance is not a useful treatment in cluster headache.

UNLABELLED: The aims of the present study were to investigate whether induction of nitrate tolerance is a useful treatment in cluster headache and to correlate any changes in attack frequency of cluster headache and nitrate-induced headache to the vascular adaptation during continuous nitrate administration. The results were compared to results obtained from studies of nitrate tolerance in healthy subjects. MATERIALS AND METHODS: 5-isosorbide-mononitrate (5-ISMN) 30 mg was administered orally three times daily for 4 weeks in nine sufferers of chronic cluster headache in a double-blind, randomized placebo-controlled cross-over design. Blood velocity in the middle cerebral artery was measured with transcranial Doppler and the diameters of the temporal and radial arteries were measured with high frequency ultrasound. The haemodynamic data were compared to changes in the frequency of cluster headache attacks and interval headaches over time. RESULTS: Tolerance was complete within 24 h in the middle cerebral arteries and after 7 days in the symptomatic temporal artery, while tolerance of the radial artery was not observed within this period. The time profiles of tolerance were almost identical to the time profiles observed in healthy subjects. A close temporal association between the disappearance of nitrate-induced headache and tolerance of the temporal artery was observed but tolerance had no effect on cluster headache attack frequency. CONCLUSIONS: Induction of tolerance to nitrates cannot be used to treat cluster headache. If pain is related to arterial dilatation the results point to extracerebral rather than cerebral arteries as the site of nociception. However, other peripheral and central pain-modulating effects of nitric oxide, the time courses of which are unknown, should also be taken into consideration.

Adult↗

PubMed2000

Nitric oxide-induced headache in patients with chronic tension-type headache.

An experimental model of headache offers unique possibilities to study the mechanisms responsible for head pain. Using the glyceryl trinitrate [GTN; nitric oxide (NO) donor] model of experimental headache, we studied the intensity, quality and time profile of headache after infusion of GTN in 16 patients with chronic tension-type headache and in 16 healthy controls. Subjects were randomized to receive intravenous infusion of GTN (0.5 microg/kg per minute for 20 min) or placebo on two headache-free days separated by at least 1 week. Headache intensity was measured on a 10-point verbal rating scale during 2 h of observation and for the next 10 h after discharge from hospital. The primary endpoints were the difference between the area under the curve (AUC-intensities x duration) for headache recorded on the day of GTN treatment and on the day of placebo treatment in patients, and in patients and controls on the days of GTN treatment. In patients, the AUC on a GTN day [2221 (1572-3704); median with quartiles in parentheses], was significantly greater than on a placebo day [730 (60-1678), P: = 0. 008]. On the GTN day, the AUC in patients [2221 (1572-3704)] was significantly higher than in controls [43 (0-972), P: = 0.0001]. In patients, peak pain intensity occurred 8 h after infusion of GTN, whereas in controls it occurred 20 min after the start of infusion. The present study demonstrates that an NO-induced biphasic response with an immediate and a delayed headache is common to chronic tension-type headache and migraine. Furthermore, the NO-induced delayed headache has the characteristics of the primary headache disorder. This suggests that NO contributes to the mechanisms of several types of primary headaches and that NO-related central sensitization may be an important common denominator in the pain mechanisms of primary headaches.

Adult↗

PubMed2000

Dipyridamole dilates large cerebral arteries concomitant to headache induction in healthy subjects.

Dipyridamole is used for secondary prophylaxis in ischemic stroke and as a vasodilator agent in myocardial scintigraphy. An important side effect to administering dipyridamole is headache. The aim of the current study was to investigate the effects of dipyridamole on cerebral blood flow, large artery diameter, and headache induction. Twelve healthy subjects were included in this single-blind placebo-controlled study in which placebo (0.9% NaCl) and dipyridamole 0.142 mg/kg x min were administered intravenously over 4 minutes 1 hour apart. Blood flow velocity in the middle cerebral artery (Vmax) was recorded by transcranial Doppler and regional cerebral blood flow in the middle cerebral artery (rCBFmca) was measured using single photon emission computed tomography and 133Xenon-inhalation. Blood pressure, heart rate, and pCO2 were measured repeatedly. Headache response was scored every 10 minutes on a verbal scale from 0 to 10 (10 = worst). Dipyridamole caused a decrease in pCO2 (P < 0.001). pCO2 corrected rCBFmca was 41.7 +/- 6.9 mL/100 g x min after placebo versus 41.2 +/- 6.9 after dipyridamole (P > or = 0.05). pCO2 corrected Vmca decreased 8.4% +/- 11.7 (P < 0.001) after dipyridamole, indicating a mean 5.6% +/- 6.7 (P = 0.005) relative increase of the arterial diameter. After dipyridamole the median peak headache score was 2 (range 0 to 7) compared with 0 (range 0 to 3) after placebo (P = 0.02). Dilatation of the middle cerebral artery outlasted the headache response. In conclusion, dipyridamole causes a modest pCO2 independent dilatation of the MCA, which is time-linked to the onset, but not to the cessation, of headache.

Adolescent↗

PubMed2000

Tension-type headache: an update on mechanisms and treatment.

Tension-type headache represents one of the most costly diseases in modern society because of its very high prevalence. Very little research on this disease has actually been carried out, and knowledge about key pathophysiological issues such as the nature and site of the noxious stimulus is surprisingly limited. As a result of this and the lack of scientific interest from the medical field, treatment is widely non-specific, very often ineffective and consists mainly of simple analgesics. The only new strategy is the pericranial injection of botulinum toxin. If current progress in our understanding of the mechanisms of tension-type headache continues, this may lead to greater scientific interest and the development of more specific and more effective drugs in the future.

Analgesics↗

PubMed2000

Regional blood flow during exercise in humans measured by near-infrared spectroscopy and indocyanine green.

Using near-infrared spectroscopy (NIRS) and the tracer indocyanine green (ICG), we quantified blood flow in calf muscle and around the Achilles tendon during plantar flexion (1-9 W). For comparison, blood flow in calf muscle was determined by dye dilution in combination with magnetic resonance imaging measures of muscle volume, and, for the peritendon region, blood flow was measured by (133)Xe washout. From rest to a peak load of 9 W, NIRS-ICG blood flow in calf muscle increased from 2.4+/-0.2 to 74+/-5 ml x 100 ml tissue(-1) x min(-1), similar to that measured by reverse dye (77+/-6 ml x 100 ml tissue(-1) x min(-1)). Achilles peritendon blood flow measured by NIRS-ICG rose with exercise from 2.2+/-0.5 to 15.1+/-0.2 ml x 100 ml(-1) x min(-1), which was similar to that determined by (133)Xe washout (2.0+/-0.6 to 14.6+/-0.3 ml x 100 ml tissue(-1) x min(-1)). This is the first study using NIRS and ICG to quantify regional tissue blood flow during exercise in humans. Due to its high spatial and temporal resolution, the technique may be useful for determining regional blood flow distribution and regulation during exercise in humans.

Coloring Agents↗

PubMed2000

No acute antimigraine efficacy of CP-122,288, a highly potent inhibitor of neurogenic inflammation: results of two randomized, double-blind, placebo-controlled clinical trials.

CP-122,288 is a highly potent inhibitor of neurogenic plasma extravasation in animal models at doses without vasoconstrictor effect. We evaluated the acute antimigraine efficacy of intravenous and oral CP-122,288 in two double-blind studies. In a crossover design, patients randomly received 31.25 microg of CP-122,288 intravenously, placebo, or both. In the oral study, patients received placebo or one of four doses of CP-122,288 between 3.125 and 312.5 microg, using a novel "up and down" design for randomization. Both studies were stopped prematurely when target efficacy could not be achieved. Responder rates were 29% for CP-122,288 versus 30% for placebo (difference, -1%; 95% CI, -24-22%; intravenous study) and an overall rate of 25% for CP-122,288 versus 0% for placebo (difference, 25%; 95% CI; 10-40%; oral study). CP-122,288 was not clinically effective at doses and plasma concentrations in excess of those required to inhibit neurogenic plasma extravasation in animals. Neurogenic plasma extravasation is unlikely to play a crucial role in the pathophysiology of migraine headache.

Administration, Oral↗

PubMed2000

Nitric oxide mechanisms in 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 as causative factors. 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 [NO] donor) and histamine (which liberates NO from the vascular endothelium), it is suggested that NO is a more likely candidate molecule. The present review examines the biology of this small messenger molecule, and the scientific evidence suggesting that it may play a key role in migraine headache. It is hypothesized that the release of NO from blood vessels, perivascular nerve endings or from brain tissue is a molecular mechanism which triggers spontaneous migraine pain. Furthermore, it has been shown that this hypothesis is supported by the recent findings that i.v. infusion of the NO synthase (NOS) inhibitor is effective in the acute treatment of migraine attacks. These novel observations indicate possible new approaches to the pharmacological treatment of migraine.

Animals↗

PubMed1999

[Randomized controlled trial of high-dose peroral methylprednisolone in attacks of multiple sclerosis].

The efficacy of glucocorticoid treatment in multiple sclerosis (MS) is uncertain. We assessed the effect of oral high-dose methylprednisolone in attacks of MS. Twenty-five patients with an attack of MS with a duration of less than four weeks were randomized to placebo, 26 patients received oral methylprednisolone (500 mg once daily for five days with a 10 days tapering period). Scripps Neurological rating scale scores differed significantly in methylprednisolone and placebo-treated patients the first three weeks (p = 0.005) and after eight weeks (p = 0.0007). Subjective symptom assessment on a visual analogue scale the first three weeks (p = 0.02) and the answers to an efficacy questionnaire administered after eight weeks (p = 0.05) also favoured a beneficial effect of methylprednisolone treatment. The risk of a new attack of MS was not influenced by the treatment at short-term follow up. No serious adverse events were seen. Oral high-dose methylprednisolone is recommended for treatment of attacks of MS.

Adult↗

PubMed1999

The relative role of genetic and environmental factors in migraine without aura.

OBJECTIVE: To clarify the relative role of genetic and environmental factors in the etiology of migraine without aura (MO). METHODS: The study population consisted of 5,360 twins, 1,013 monozygotic (MZ) and 1,667 same-gender dizygotic (DZ) twin pairs, from the population-based Danish Twin Registry. A total of 87% completed a simple validated questionnaire screening for migraine. All twin pairs, in whom at least one twin had self-reported migraine or severe headache with accompanying symptoms, were interviewed via telephone by a physician. Ninety percent of the eligible twins were interviewed. Probandwise concordance rates and correlations in liability were calculated, and structural equation model-fitting analyses were applied to quantitate the relative role of genetic and environmental factors in the etiology of MO. RESULTS: The probandwise concordance rate was higher in MZ than DZ twin pairs (0.43 versus 0.31; 95% CI, 0.36 to 0.49 versus 0.26 to 0.36). The correlation in liability was higher in MZ than in DZ twin pairs (0.62 versus 0.41; 95% CI, 0.50 to 0.74 versus 0.29 to 0.53). Structural equation model fitting indicated a highly significant genetic component, because a model with both genetic and environmental components fitted significantly better than a model with only environmental components. The best fitting model implied that the liability to MO resulted from additive genetic effects (61%; 95% CI, 49 to 71%)) and individual-specific environmental effects (39%; 95% CI, 29 to 51%). CONCLUSION: This study indicates that genetic factors play a role in the etiology of migraine without aura. The genetic variability is additive, with a negligible contribution of nonadditive genetic effects. The genetic contributions were similar in men and women despite a higher prevalence in women. Environmental factors are equally important and these factors are individual to the migraineurs.

Adolescent↗