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Biomedical subjects

P G Andersson

Publications and source records attributed to P G Andersson.

At least 19 recordsLinked to original sources

Remote dipole effects as a means to accelerate [Ru(amino alcohol)]-catalyzed transfer hydrogenation of ketones.

A new generation of 2-aza-norbornyl amino alcohol ligands for the catalytic transfer hydrogenation reaction of aromatic ketones was synthesized. Extremely active catalysts were formed by introducing a ketal functionality at the rear end of the ligand. Acetophenone was reduced in 96% ee at low catalyst loading, substrate to catalyst ratio, S/C 5000, within 90 minutes with isopropyl alcohol as the hydrogen donor. It was found that the dioxolane substituent in the ligand increased the turnover frequency, TOF50, from 1050 h(-1) to 3000 h(-1) at an S/C ratio of 1000. Introduction of a methyl group at the carbinol carbon resulted in TOF50 as high as 8500 h(-1). Transfer hydrogenation of a range of aromatic ketones was evaluated and found to reach completion within 30 minutes at room temperature, and excellent enantioselectivity, up to 99 % ee, was obtained. A possible explanation for the enhanced activity was provided by density functional calculations, which showed that the presence of a remote dipole in the ligand lowered the transition state energy.

Journal Article↗

[Familial occurrence of cluster headache].

The familial occurrence of cluster headache was assessed in 421 probands with cluster headache, diagnosed according to the diagnostic criteria of the International Headache Society. The probands were from a neurological clinic and two departments of neurology. They received a mailed questionnaire regarding the presence of cluster headache among their relatives. All possibly affected relatives were interviewed by telephone. The questionnaire response rate was 88% (370/421). Seven probands belonged to three families. Familial occurrence of cluster headache was confirmed in 7% (25/366) of the families. Compared with the general population, first degree relatives of probands with cluster headache had a 14-fold increased risk of cluster headache, after standardization for sex and age. The second degree relatives had a twofold increased risk of cluster headache. The increased familial risk of cluster headache strongly suggests that cluster headache has a genetic cause.

Adult↗

Cluster headache is an autosomal dominantly inherited disorder in some families: a complex segregation analysis.

We investigated the mode of inheritance of cluster headache in 370 families. The probands were from a neurological clinic in Jutland and two departments of neurology in Copenhagen County, Denmark. The criteria of the International Headache Society were used. The patterns of segregation of cluster headache were assessed by complex segregation analysis performed with the computer program POINTER. Of the 370 probands with cluster headache, 25 had 36 relatives with cluster headache. The segregation analysis suggests that cluster headache has an autosomal dominant gene (p < 0.10) with a penetrance of 0.30-0.34 in males and 0.17-0.21 in females. The gene is present in 3 to 4% of males and 7 to 10% of females with cluster headache. An autosomal dominant gene has a role in cluster headache in some families.

Adolescent↗

Familial occurrence of cluster headache.

The familial occurrence of cluster headache was assessed in 421 patients with cluster headache, diagnosed according to the operational diagnostic criteria of the International Headache Society. The patients were recruited from a neurological clinic and two departments of neurology, covering east central Jutland and Copenhagen County respectively. They received a mailed questionnaire regarding the presence of cluster headache among their first and second degree relatives. All possibly affected relatives were interviewed by telephone. The response rate to the questionnaire was 88% (370/421). Seven patients belonged to three families. A positive family history of cluster headache was found in 7% (25/366) of the families. Compared with the general population, the first and second degree relatives of the 370 patients with cluster headache had a 14-fold and twofold increase in the risk of having cluster headache after standardisation for sex and age. This increase in familial risk strongly suggests that cluster headache has a genetic cause.

Adult↗

Clinical characteristics of migraine and episodic tension-type headache in relation to old and new diagnostic criteria.

Eighty-one patients were diagnosed as having migraine, tension headache or both according to previously used criteria. Then we performed a standardized interview to determine the frequency and severity of headache characteristics used in the new operational diagnostic criteria of the International Headache Society (IHS). In every patient the original diagnosis fulfilled also the IHS criteria, but in 9 patients the criteria were only fulfilled in half or less of the attacks, and applying the IHS criteria they also achieved an additional diagnosis. In one patient these attacks did not fulfill the pain criteria and in 8 (4 migraine, 4 tension headache) they did not fulfill the criteria for accompanying symptoms. Overall the IHS criteria are sensitive and specific, but they may possibly be improved with regard to accompanying symptoms. The present study suggests that recording of frequency and graded severity of characteristics using a headache diary may further improve the distinction between the different types of headache.

Female↗

Double-blind study of naproxen vs placebo in the treatment of acute migraine attacks.

Naproxen was compared with placebo in a double-blind, crossover trial in classic and common migraine. The trial was terminated at a fixed date; 37 patients had entered, 5 of whom were excluded. Naproxen was given as 750 mg at the first symptom of the attack, a total of 1250 mg per 24 h was allowed. Patients were followed for six attacks or three months in each phase, whichever came first. The severity of the headache was significantly less with naproxen in the first 2 h of the attack (p = 0.047), whereas there was no difference when the whole attack was considered. Significantly more patients preferred naproxen (p = 0.042). Side effects occurred in five patients, causing withdrawal of one patient while on naproxen.

Acute Disease↗

Symptoms of classic migraine attacks: modifications brought about by metoprolol.

There is little information available concerning whether, and to what extent, migraine-prophylactic agents interfere with the symptoms of migraine attacks. The present study is a placebo-controlled, double-blind study concerning metoprolol in classic migraine. The data refer to the symptoms of single migraine attacks. During metoprolol treatment more attacks were characterized as mild (p = 0.002), and mean global rating (an integrated estimate of headache intensity and of other discomfort) was lower (4.2 versus 5.2, p = 0.003). The mean headache intensity per attack (1.97 versus 2.15) and the mean duration (5.5 versus 6.8 h) were not significantly different. Consumption of analgesics per attack was lower during metoprolol treatment (0.6 versus 1.1; p = 0.02). Attacks with associated symptoms accompanying the headache were fewer during metoprolol treatment (p = 0.014). Total visual and non-visual aura symptoms occurred with similar frequency, but scintillations and paraesthesia were more frequent during metoprolol treatment, whereas speech disturbances were less frequent. In spite of lower consumption of analgesics, the symptoms appeared milder during metoprolol than during placebo. The pattern of changes indicates that metoprolol exerts its action via the sympathetic nervous system; peripheral vasoconstriction is hardly the underlying mechanism of action.

Adolescent↗

Classic migraine: effective prophylaxis with metoprolol.

Metoprolol slow-release tablets (Durules), 200 mg, given once daily in the morning were compared with placebo in the prophylaxis of classic migraine. The trial comprised eight Scandinavian neurologic centres and was designed as a double-blind cross-over study with 4 weeks' run-in, four weeks washout, and 8 weeks of either treatment. Seventy-seven patients with two to eight migraine attacks per month were entered in the trial, and 73 completed it. A total of 1119 attacks with aura symptoms and 374 without were recorded. Metoprolol was significantly better than placebo with regard to the total frequency of attacks (1.8 versus 2.5 attacks/4 weeks), mean duration of attacks (6.0 versus 8.0 h/attack), mean global rating, and consumption of analgesics per attack. Similar differences could be shown for attacks with aura symptoms alone, except for the duration of attacks. Metoprolol is the first drug for which a prophylactic effect in classic migraine has been convincingly demonstrated.

Adolescent↗

Dihydroergotamine nasal spray in the treatment of attacks of cluster headache. A double-blind trial versus placebo.

A double-blind trial of dihydroergotamine (DHE) nasal spray compared with placebo was carried out in patients with cluster headache. Twenty-five patients were included in the trial. In three patients, all receiving DHE, the pain attacks ceased after five attacks. In the other 22 patients, 133 attacks were treated with placebo and 137 attacks with DHE nasal spray (dosage, 1 mg of DHE). The trial showed that the treatment given has no effect on the attack frequency or the duration of the single attack. However, the treatment had a significant effect on the intensity of the single attacks. It can be concluded that the trial should be repeated, using a larger dosage of DHE. This should be ethically justifiable, since none of the patients had any adverse reactions locally in the mucous membrane of the nose or systemically.

Administration, Intranasal↗

Migraine in patients with cluster headache.

One hundred and twenty seven patients with cluster headache have been compared with 122 patients with migraine. Twenty of the patients with cluster headache have had migraine attacks but only 2 still have migraine attacks after the onset of cluster headache. No migraine patients had cluster headache. Among the 127 patients with cluster headache, one of the parents suffered from cluster headache in 4.7% of the cases. Among the 122 patients with migraine, 0.8% had a parent with cluster headache. Among the 122 patients with migraine 54.9% had parents with migraine, and in the cluster headache group 23.6% of the patients had one parent with migraine. The coexistence of migraine and cluster headache is rare. The two types of headache, as far as the heredity pattern is concerned, are independent entities.

Adolescent↗

Prophylactic treatment of classical and non-classical migraine with metoprolol--a comparison with placebo.

A double-blind investigation with parallel groups was carried out in three Danish neurological clinics to evaluate the effect of metoprolol (Beloc, Betaloc, Seloken) versus placebo in migraine patients. 71 patients were included; 62 completed the study. The following parameters were used in the evaluation: frequency of headache attacks, days with migraine, severity score (days X intensity), and the consumption of pain-relieving tablets. The results of the study show that metoprolol 200 mg in Durules (a controlled release formulation) once daily is more effective regarding all evaluated parameters than placebo and that metoprolol is well tolerated.

Adolescent↗

Propranolol and femoxetine, a HT-uptake inhibitor, in migraine prophylaxis. A double-blind crossover study.

The prophylactic effect of the 5-HT uptake inhibitor femoxetine was compared with propranolol (Frekven R) in a double-blind crossover trial of 6 months duration. Forty-nine patients commenced the trial. Twelve patients withdrew because of drug failure or failure to attend checkups (6), side effects (4) or other non-drug related causes (2). In the 37 patients who completed the trial there was no significant difference between propranolol 160 mg and femoxetine 400 mg with respect to the number of headache days or the number of migraine attacks during the last 2 months of each treatment, Propranolol, however, was superior to femoxetine when the headache index was used (P less than 0.05). The study has shown that partial depletion of thrombocyte 5-HT by a 5-HT uptake inhibitor does not lead to a marked improvement in all patients contrary to what might be expected from the 5-HT hypothesis of migraine. Nevertheless, due to the infrequent subjective side effects associated with femoxetine treatment it may be a valuable prophylactic drug to a subgroup of migraine patients.

Adult↗