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Biomedical subjects

J Olesen

Publications and source records attributed to J Olesen.

At least 91 records · Page 5Linked to original sources
PubMed2000

Possible risk factors and precipitants for migraine with aura in discordant twin-pairs: a population-based study.

The aim of the present study was to detect possible risk factors in migraine with aura (MA) by analysis of discordant twin-pairs. In a recent population-based twin study we established that environmental factors account for approximately 50% of the variation in liability to MA. A cohort of 5,360 same-gender twin-pairs from the general population was screened for migraine. All twin-pairs with possible migraine were interviewed by a physician. A questionnaire provided information about living conditions and lifestyle. Of the 169 discordant twin-pairs 51 were monozygotic and 118 were dizygotic twin-pairs. Several putative risk factors-schooling, education, marital status, smoking status and alcohol consumption-showed no association with MA. The presence of migraine without aura or tension-type headache did not increase the risk of MA. Stress and mental tension, and bright light precipitated attacks of MA in, respectively, 44% and 28% of the twins.

Alcohol Drinking↗
PubMed2000

Possible mechanisms of glyceryl-trinitrate-induced immediate headache in patients with chronic tension-type headache.

Nitric oxide (NO) plays an important role in the pathophysiology of primary headaches including chronic tension-type headache (CTTH). Thus, a NO synthase inhibitor reduces headache and muscle hardness while the NO donor glyceryl trinitrate (GTN) causes more headache in patients than in healthy controls. Sensitization of myofascial pain pathways is important in CTTH, and the aim of the present study was to investigate if such mechanisms may also explain GTN-induced immediate headache in patients with CTTH. In a randomized, double-blind, crossover study 16 patients with CTTH and 16 healthy subjects received intravenous infusion of GTN (0.5 microg/kg per min for 20 min) or placebo on two headache-free days separated by at least 1 week. Muscle hardness, myofascial tenderness, mechanical and heat pain thresholds were measured at baseline and at 60 min and 120 min after start of infusion. In patients, GTN infusion resulted in a biphasic response with immediate headache and more pronounced delayed headache. A similar but less pronounced response was seen in controls. There was no difference between GTN and placebo regarding muscle hardness, myofascial tenderness or pressure and heat pain thresholds in either patients or controls (P>0.05). The unchanged sensitivity of pericranial myofascial pain pathways indicates that peripheral and central sensitization is not involved in the mechanisms of GTN-induced immediate headache.

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↗
PubMed1999

Phosphorylation regulates in vivo interaction and molecular targeting of serine/arginine-rich pre-mRNA splicing factors.

The SR superfamily of splicing factors and regulators is characterized by arginine/serine (RS)-rich domains, which are extensively modified by phosphorylation in cells. In vitro binding studies revealed that RS domain-mediated protein interactions can be differentially affected by phosphorylation. Taking advantage of the single nonessential SR protein-specific kinase Sky1p in Saccharomyces cerevisiae, we investigated RS domain interactions in vivo using the two-hybrid assay. Strikingly, all RS domain-mediated interactions were abolished by SKY1 deletion and were rescuable by yeast or mammalian SR protein-specific kinases, indicating that phosphorylation has a far greater impact on RS domain interactions in vivo than in vitro. To understand this dramatic effect, we examined the localization of SR proteins and found that SC35 was shifted to the cytoplasm in sky1Delta yeast, although this phenomenon was not obvious with ASF/SF2, indicating that nuclear import of SR proteins may be differentially regulated by phosphorylation. Using a transcriptional repression assay, we further showed that most LexA-SR fusion proteins depend on Sky1p to efficiently recognize the LexA binding site in a reporter, suggesting that molecular targeting of RS domain-containing proteins within the nucleus was also affected. Together, these results reveal multiple phosphorylation-dependent steps for SR proteins to interact with one another efficiently and specifically, which may ultimately determine the splicing activity and specificity of these factors in mammalian cells.

Animals↗
PubMed1999

A randomized, controlled trial of oral high-dose methylprednisolone in acute optic neuritis.

OBJECTIVE: To assess the efficacy of oral high-dose methylprednisolone in acute optic neuritis (ON). BACKGROUND: It has been determined that oral high-dose methylprednisolone is efficacious in attacks of MS. METHODS: A total of 60 patients with symptoms and signs of ON with a duration of less than 4 weeks and a visual acuity of 0.7 or less were randomized to treatment with placebo (n = 30) or oral methylprednisolone (n = 30; 500 mg daily for 5 days, with a 10-day tapering period). Visual function was measured and symptoms were scored on a visual analog scale (VAS) before treatment and after 1, 3, and 8 weeks. Primary efficacy measures were spatial vision and VAS scores the first 3 weeks (analysis of variance with baseline values as the covariate), and changes in spatial vision and VAS scores after 8 weeks. A significance level of p < 0.0125 was employed. RESULTS: The VAS score (p = 0.008) but not the spatial visual function (p = 0.03) differed in methylprednisolone- and placebo-treated patients during the first 3 weeks. After 8 weeks the improvement in VAS scores (p = 0.8) and spatial visual function (p = 0.5) was comparable with methylprednisolone- and placebo-treated patients. A post hoc subgroup analysis suggested that patients with more severe baseline visual deficit and patients treated early after onset of symptoms had a more pronounced response to treatment. The risk of a new demyelinating attack within 1 year was unaffected by treatment. No serious adverse events were seen. CONCLUSION: Oral high-dose methylprednisolone treatment improves recovery from ON at 1 and 3 weeks, but no effect could be demonstrated at 8 weeks or on subsequent attack frequency.

Acute Disease↗
PubMed1999

[Familial occurrence of chronic tension headache].

Chronic tension-type headache occurs in 3% of the Danish population. the aetiology remains an enigma, even though it is one of the most frequent illnesses with chronic pain. A family study indicates the importance of genetic factors. Compared with the general population, first degree relatives (parents, siblings and children) of probands with chronic tension-type headache have a three-fold significantly increased risk of chronic tension-type headache, while spouses had no increased risk. Complex segregation analysis indicates multifactorial inheritance. Thus, a combination of genetic and environmental factors causes chronic tension-type headache.

Adult↗
PubMed1999

Effect of inhibition of nitric oxide synthase on chronic tension-type headache: a randomised crossover trial.

BACKGROUND: Studies in animals have shown that nitric oxide plays an important part in central sensitisation and that inhibitors of nitric oxide synthase (NOS) decrease sensitisation in models of persistent pain. The efficacy of inhibitors of NOS has not been tested in patients with tension-type chronic headache. We aimed to show whether N(G)-monomethyl-L-arginine hydrochloride (L-NMMA), an inhibitor of NOS, is effective in relieving pain in such patients. METHODS: We undertook a randomised double-blind, crossover trial of 16 patients with chronic-tension-type headache. Patients were assigned intravenous infusion of 6 mg/kg L-NMMA or placebo on 2 days separated by at least 1 week in a randomised order. Headache intensity was measured on a 100 mm visual analogue scale, and on a verbal rating scale at baseline and at 30 min, 60 min, and 120 min after start of treatment. The primary endpoint was reduction of pain intensity on the visual analogue scale by the active treatment compared with placebo. FINDINGS: L-NMMA reduced pain intensity on the visual analogue scale 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). Pain intensity on the verbal rating scale was also significantly lower for treatment with L-NMMA than for treatment with placebo (p=0.02). INTERPRETATION: Inhibition of NOS had an analgesic effect in chronic tension-type headache. Further tests are required before clinical application.

Adult↗
PubMed1999

Evidence of a genetic factor in migraine with aura: a population-based Danish twin study.

We studied the genetic influence on cause of migraine with aura (MA) by analyzing a twin population. The twin sample consisted of 2,026 monozygotic (MZ) twins and 3,334 same-sex dizygotic (DZ) twins, born from 1953 to 1960, from the population-based New Danish Twin Register. A validated questionnaire was used to screen for migraine, the response rate being 87%, and similar among MZ and DZ twins. All twin pairs with at least 1 twin with possible MA were interviewed by a physician experienced in headache diagnoses. The answers from the questionnaire as well as the zygosity of the twins were blinded for the interviewer. A total of 211 twin pairs were identified, of whom 77 pairs were MZ and 134 pairs were DZ. The lifetime prevalence of MA was 7% and with a male-to-female ratio of 1:1.1. The pairwise concordance rates were significantly higher in MZ (34%) than in DZ twin pairs (12%), emphasizing the importance of genetic factors in MA. However, environmental factors are also important, as the pairwise concordance rate was less than 100% in MZ twin pairs. The recurrence risk of MA was 50% in MZ and 21% in DZ twin pairs. In nontwin siblings, the recurrence risk of MA is 27%, which is similar to the recurrence risk in DZ twins. This indicates that MA is not developed due to specific environmental factors shared by the twins.

Adult↗