Hypnic headache syndrome: clinical aspects of eight patients in Brazil.
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Biomedical subjects
Publications and source records attributed to Y D Fragoso.
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We assessed the efficacy and safety of oral single doses of 0.5 and 1 g metamizol vs. 1 g acetylsalicylic acid (ASA) in 417 patients with moderate episodic tension-type headache included in a randomized, double-blind, placebo- and active-controlled, parallel, multicentre trial. Eligibility criteria included 18-65 years of age, history of at least two episodes of tension-type headache per month in the 3 months prior to enrollment, and successful previous pain relief with a non-opioid analgesic. Treatment arms were metamizol 0.5 g (n = 102), metamizol 1 g (n = 108), ASA 1 g (n = 102) and placebo (n = 105). The analgesic efficacy of 0.5 and 1 g metamizol vs. placebo was highly statistically significant (alpha: 0.025; one-sided) for sum of pain intensity differences, maximum pain intensity difference, number of patients with at least 50% pain reduction, time to 50% pain reduction, maximum pain relief and total pain relief. A trend towards an earlier onset of a more profound pain relief of 0.5 and 1 g metamizol over 1 g ASA was noticed. All medications including placebo were almost equally safe and well tolerated.
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CONTEXT: The difficult management of chronic daily headache and the lack of clinical trials for this medical condition led the authors to perform this study. Gabapentin has been successfully used for a variety of chronic pain conditions and therefore may be of use in the treatment of chronic headache. OBJECTIVE: To assess the efficacy and safety of low doses of gabapentin in cases of chronic daily headache. DESIGN: Open-label study on a series of cases of chronic daily headache. PATIENTS: Twenty-one consecutive patients with primary headache lasting 4 or more hours a day, at least 15 days per month, were invited to participate in this open trial. They were treated with low doses of gabapentin for sufficient time to lead to a headache-free period of at least 7 consecutive days. A minimum of 1 follow-up visit and 1 phone call were made in the subsequent 6-9 months. MEASUREMENTS: A simple "Patient Impression of Change" was used to evaluate the results. Patients were also invited to compare this treatment to previous ones, whenever possible. RESULTS: The efficacy of the treatment with gabapentin was rated as "excellent" by 19% of the patients, "good" by 47.6%, "fair" by 19%, and "poor" by 14.4%. CONCLUSIONS: Despite the inherent limitations of such a small open trial, the authors concluded that ratings of excellent and good by two thirds of this population of patients with chronic daily headache should encourage the setup of a large double-blind, multicentric, placebo-controlled trial of low doses of gabapentin for chronic daily headache.
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High density lipoprotein (HDL) has been implicated in the process of reverse cholesterol transport,by which surplus cholesterol is removed from peripheral tissues and transported to the liver for excretion. It has been suggested that some subfractions of HDL may have a particular role in this process, though the underlying mechanism remains unclear. The present study was aimed at investigating the role of specific subfractions of HDL in reverse cholesterol transport. The interconversion of HDL subfractions in normal and cholesterol-loaded rabbits was studied in vivo. Rabbit HDL was separated by heparin-Sepharose affinity chromatography into six subfractions (HDL(I)-HDL(VI)), which were progressively enriched with apolipoprotein E (apo E), and varied in diameter and composition. Total HDL and its subfractions were individually labelled with 14C sucrose and injected in the rabbits. When rabbits which were not acutely loaded with [3H]cholesterol were injected with 14C-HDL(I), 70% of the label remained in this fraction while less than 5% was recovered in HDL(VI), containing the largest particles and those most enriched in apo E. No label was detectable in the liver of these animals. In rabbits which had received a prior loading of cholesterol, an average of only 18.3% of the 14C label was present in HDL(I) while approx. 40% of the label was recovered in HDL(VI). On average, 5.1% of the total 14C injected in these rabbits was recovered in the liver. It is concluded that two alternative routes for reverse cholesterol transport may be operative. While a continuous cholesterol-clearance route may be provided by particles of HDL of intermediate size, another route may be operative for clearance of excess cholesterol loaded into peripheral endothelial cells.
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Apolipoprotein (apo) E plays an important role in mediating high-density lipoprotein (HDL) cholesterol transport and uptake by the liver. Evidence for and against the existence of conventional liver receptors for HDL containing apoE have been reported, although the selective uptake of the cholesterol moiety of HDL has been demonstrated. The present study investigated the hepatic uptake of subfractions of HDL separated on the basis of their apoE content. Rabbit HDL and its apoE-rich and apoE-poor subfractions, separated by heparin-Sepharose affinity chromatography, were labelled in their apoprotein moieties with [14C]sucrose and in their cholesteryl ester moiety with 3H. No binding of either subfraction to rabbit liver membranes could be detected. With cultured HepG2 cells, however, there was a high uptake of 3H but a very low uptake of 14C from both HDL subfractions, demonstrating that selective uptake was operating. Addition of unlabelled apoE-poor HDL inhibited the uptake of both labels from the two subfractions to the same extent. These studies, which differed from previously reported investigations by employing native homologous HDL subfractions of known apolipoprotein composition, demonstrated that apoE is not directly involved in the selective uptake of HDL cholesterol by the liver. In the absence of specific binding sites on liver membranes, it is suggested that an alternative mechanism might exist for the clearance of HDL cholesterol from the plasma.
An apolipoprotein (apo) E-rich and an apo E-poor fraction of high-density lipoprotein (HDL) were isolated from four healthy men by heparin-Sepharose affinity chromatography. On a cholesterol basis, the apo E-poor HDL fraction contained a third more alpha- and gamma-tocopherol and about a third less alpha- and beta-carotene than the apo E-rich HDL fraction. Plasma concentrations of HDL cholesterol were highly correlated with the contribution of the apo E-rich HDL subfraction to total HDL alpha-tocopherol (r = -0.990, P < 0.001).
The effect of dietary supplementation with evening primrose oil (containing 70% gammalinolenic acid) on the concentration of plasma lipids and lipoproteins of the New Zealand White rabbit was investigated. No significant changes were observed in the concentrations of plasma cholesterol or triglycerides during the treatment, although an increase in high density lipoprotein (HDL) cholesterol (P < 0.01) was observed at 4 weeks of evening primrose oil intake and 2 weeks after withdrawal. However, when HDL subpopulations were resolved by gradient gel electrophoresis, major alterations were observed in the distribution of HDL subfractions. These included an increase in HDL2b (P < 0.001) and HDL3c (P < 0.001) and the appearance of very large particles of HDL. These findings suggest that supplementation of diets with n-6 fatty acids may be effective in the long-term prevention of atherosclerosis.
Our group has previously reported significant changes in the incorporation of precursors into glycerophospholipids, particularly phosphatidylserine, in polymorphonuclear cells obtained from the peripheral blood of cluster headache patients, when compared with controls. The potential of these results led to further work using both the previous methodology and a modified isolation technique to obtain polymorphonuclear cells in as pure a state as possible. Neither the new results obtained using the original technique, nor the results with high purity polymorphonuclear cells from controls and cluster headache patients, confirm the marked changes in precursor uptake into glycerophospholipids originally reported.
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As recently demonstrated by our group, polymorphonuclear cells (PMNs) from cluster headache patients have an increased ability to incorporate arachidonic acid (AA) and L-serine into phosphatidylserine (PS). To evaluate whether there is an increased incorporation into PS also from fatty acids not involved in eicosanoid metabolism, PMNs from controls (n = 14) and cluster headache patients (n = 12) were incubated with (1-14C)oleic acid. After 1 h 2.7% +/- 1.1 (mean value +/- SD) of the glycerophospholipid radioactivity was found in PS in controls, whereas 4.2% +/- 1.2 was found in cluster headache patients (p less than 0.005). For phosphatidylcholine (PC) the corresponding figures were 74.2 +/- 5.4 in controls and 66.7 +/- 7.6 in cluster headache patients (p less than 0.01). The results suggest that the de novo biosynthesis of PS is increased and the biosynthesis of PC is decreased in cluster headache. The results may have an effect on the role of PS as an obligate protein kinase C activator.
Vasoactive metabolites deriving from arachidonic acid (AA) have been considered as putative mediators in the pathogenesis of various types of headache. In the present study we therefore compare the ability to synthesize AA containing precursor phospholipids in polymorphonuclear cells (PMNs) from healthy controls and cluster headache patients. 3.7% +/- 1.4 (mean +/- SD) of the (1-14C)AA incorporated into total PMN glycerophospholipids (GPLs) was recovered in the phosphatidylserine (PS) in a group of cluster headache patients (n = 12). This was almost twice the value of 1.9% +/- 0.8% found in a corresponding group of 24 healthy controls (p less than 0.001). A significant decrease in the incorporation of (1-14C)AA into phosphatidylcholine (PC) (p less than 0.01) and an increase in the incorporation of (1-14C)AA into phosphatidyletanolamine (PE) (p less than 0.05) were also found in cluster headache patients when compared to the control group. The increased incorporation of (1-14C)AA into PS in PMNs from this group of patients is interesting because PS plays an important role in the activation of protein kinase C, an enzyme involved in transmembrane signalling. The clinical implications of the present findings in cluster headache, if any, cannot yet be defined.
It has recently been demonstrated by our group that polymorphonuclear cells (PMNs) from cluster headache patients incorporate more arachidonic acid (AA) into phosphatidylserine (PS) than PMNs from controls. In the present report, the incorporation of L-(U-14C)serine into PS in PMNs from 14 healthy volunteers and 12 cluster headache patients was studied. PMNs from controls incorporated 1194 +/- 578 (mean +/- SD) cpm of L-(U-14C)serine into PS, 268 +/- 292 cpm into phosphatidylethanolamine, and 57 +/- 71 cpm into sphingomyeline. The corresponding figures in cluster headache patients were 2365 +/- 841 cpm, 291 +/- 207 cpm, and 88 +/- 66 cpm, respectively. Incorporation of L-(U-14C)serine into PS was significantly increased (p less than 0.0004) in PMNs from cluster headache patients, whereas no significant difference was seen in other lipids. The results confirm that patients with cluster headache have an increased incorporation of precursors into PS in isolated PMNs, and they indicate that this is due to an increased de novo synthesis of PS.
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A 56-year-old, previously reported woman with cluster headache-like headache with bouts of unilateral (the side of predominance changing through the years) severe headache had a familial history (three generations) of partial Hageman factor deficiency and bleeding episodes. A giant aneurysm was found to be lodged in the anterior communicating artery on the left side. Clinically, the features were atypical for cluster headache: onset at a young age (14 years), episodes of retrobulbar neuritis appearing at the side of pain, etc. Studies of forehead sweating indicated that the right side was the pathologic one, from an autonomic point of view, as did pupillometric studies. However, during attacks, which were left-sided at the time, forehead sweating was marked laterally on the left side and on the upper eyelid, but not on the right. The "signal" usually reaching the autonomically stigmatized side during attacks of cluster headache, therefore, did not seem to reach the sweat glands on that (the right) side during the attack in the present case. This headache may, therefore, be distinct from cluster headache, both from a clinical and from an autonomic function point of view.
A 51-year-old male cluster headache patient had during five bouts in the course of 11 years always had the headache attacks on the left side. Autonomic abnormalities were, however, present on the right side. Pupillometrically, there was thus a Horner-like syndrome on the right (non-symptomatic) side, with miosis and a relatively more marked dilatation of that eye subsequent to topical application of a directly working sympathomimetic agent (phenylephrine) than after an indirectly working one (hydroxyamphetamine), whereas this was not the case on the symptomatic side. The findings on evaporimetry were not as clear-cut as the pupillometric findings; however, even facial sweating was consistent with a pathologic condition on the right (non-symptomatic) side. A primary dichotomy of pain and autonomic signs (that is, not due to change of side of pain localization) thus seems to be present in this case.