Gender ratio of migraine without aura: observations over time

Abstract Migraine without aura is typically considered a female condition. The purpose of this study was to determine if there have been any changes in the female-to-male ratio of the disease over time. We included in the study all patients with migraine without aura (n=3457) referred to the Parma University Headache Centre between 1976 and 1995. They were divided into subgroups with respect to gender and year-range of onset of migraine (before 1960, in the 1960s, in the 1970s, in the 1980s, and between 1990 and 1995). Gender ratio ranged from 3.6:1 (in patients with onset before 1960) to 2.8:1 (in patients with onset in the 1980s), with no statistically significant changes during the observation period.     

Minimally invasive treatment of acute biliary pancreatitis

Background: Stones of the common bile duct are the most important factor in acute pancreatitis (AP). Endolaparoscopic surgery plays a well-recognized role in the treatment of this pathology. Methods: From January 1992 to December 1995 we observed 62 cases of acute biliary pancreatitis (ABP). In 57 cases (= 93.4%) we proposed a minimally invasive treatment, based on performance of endoscopic retrograde cholangiopancreatography (ERCP) combined with endoscopic sphincterotomy (ES) and then of laparoscopic cholecystectomy (LC). Results: ERCP was attempted in emergency in 40/57 cases and successfully done in 34 cases. An ES was performed in all but two cases. In 51 patients we performed LC. The overall morbidity was 8.9% with no mortality. Conclusions: In the case of ABP early treatment can achieve the restoration of patency of the papilla, reducing the risk of associated cholangitis and the development of pancreatic necrosis. The cholecystectomy prevents the risk of relapse of ABP.     

Differential effects of beclobrate on lipid/lipoprotein distribution in normal and hypercholesterolemic rats

Beclobrate, a new fibric acid derivative, displays remarkable lipid lowering activity in rodents. In order to evaluate changes in the distribution and liver handling of lipoproteins, beclobrate was tested in rats fed on a normal or hypercholesterolemic diet. On the normal diet, beclobrate lowered total plasma cholesterol by 22-33.4% (10-50 mg/kg); the cholesterol reduction occurred mainly in high density lipoproteins (HDL) (by 24-45% with the three tested doses). The metabolic clearance of 125I-labelled beta-very low density lipoproteins (beta-VLDL) injected into these animals almost doubled (0.20 1/h vs. 0.13 1/h in controls) after treatment with 20 mg/kg of beclobrate. In addition, beclobrate administration dramatically increased the activity of the high-affinity receptors for beta-VLDL in isolated liver membranes (Bmax: 208 +/- 17.6 vs. 146 +/- 2.6 ng/mg of protein for controls). On the hypercholesterolemic diet, beclobrate treatment (50 mg/kg) was associated with a 25% reduction in total cholesterol accompanied, however, by a 166% rise in HDL cholesterol. In these animals, the composition of VLDL, typically cholesterol-enriched, became close to normal. The increased HDL was characterized by a remarkable enrichment with particles containing apolipoprotein E (apo E), which is compatible with either an improved peripheral cholesterol removal or an enhanced direct secretion of apo E. The two models offer different opportunities for evaluating the mechanism of action of this new lipid lowering agent. Lipoprotein catabolism and receptor-mediated clearance were characteristically improved in normolipidemic rats whereas major effects on HDL metabolism could be demonstrated in hypercholesterolemic rats.     

Partial seizures and migraine

Epilepsy and migraine, despite some common features, have quite different pathophysiological mechanisms. Studies carried out on large population samples have shown that the relationships between migraine and epilepsy may be of the following type: associated attacks, with migraine and seizures occurring quite independently of one another; combined attacks, with the two types of attacks succeeding one another in time; basilar artery migraine with seizures and marked EEG abnormalities; benign epilepsies with occipital discharges, migraine and intercalated seizures. We report four cases of particular interest.     

Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.     

Abnormal dexamethasone suppression test in daily chronic headache sufferers

The dexamethasone suppression test (DST) was administered in 48 daily chronic headache (DCH) sufferers, 37 of whom also suffered from mild to severe depression. In 14 of 48 subjects (29.2%), cortisol values at 1600h were greater than 50 ng/ml, despite normal suppression at 0800h. The escapers showed basal cortisol values and (Depression scale) scores on the Minnesota Multiphasic Personality Inventory higher than suppressors. Thus, a group of DCH sufferers appeared to share a biochemical defect often seen in endogenous depression. The escape from dexamethasone suppression could be a psychobiological indicator of vulnerability to develop depressive disorder and/or chronic pain complaints.     

The patient–physician relationship in the approach to therapeutic management

Neurological Sciences - Recent epidemiological investigations have demonstrated that migraine, and more generally primary headaches, are underdiagnosed and poorly treated. To tackle and resolve...     

Metabotropic Glutamate Receptors Inhibiting Excitatory Synapses in the CA1 Area of Rat Hippocampus

In the CA1 region of hippocampal slices prepared from young adult rats, we studied the ability of several specific agonists of metabotropic glutamate receptors (mGluRs) to depress excitatory synaptic transmission at the CA3–CA1 pyramidal cell synapses. Three groups of mGluRs have been described: group 1 (mGluR1 and 5) receptors are positively coupled to phospholipase C whereas group 2 (mGluR2 and 3) and group 3 (mGluR4, 6, 7 and 8) receptors are negatively coupled to adenylate cyclase. We found that the broad-spectrum agonist (1 S ,3R)-1-aminocyclopentyl-1,3-dicarboxylate and the group 1-specific agonist ( R,S )-dihydroxyphenylglycine both reversibly inhibited evoked field excitatory postsynaptic potentials, indicating the involvement of group 1 mGluRs. ( R,S )-3,5-dihydroxyphenylglycine presumably inhibited transmission via a presynaptic mechanism, as whole-cell voltage-clamp recordings revealed that inhibition of the synaptic transmission was always accompanied with an increase in paired-pulse facilitation. Treatment with a specific blocker of mGluR1 receptors, the phenylglycine derivative ( S )-4-carboxyphenylglycine, was without effect on the (1 S ,3 R )-1-amino-cyclopentyl-1,3-dicarboxylate-induced depression of the field excitatory postsynaptic potentials, strongly suggesting that mGluR5 receptors are responsible for the (1 S ,3 R )-1-aminocyclopentyl-1,3-dicarboxylate effect. Two selective agonists of group 2 mGluRs, (2 S ,1' s ,2' s )-2-(2'-carboxycyclopropyl)glycine and 4-carboxy-3-hydroxyphenylglycine, were totally ineffective in blocking CA3-CA1-evoked synaptic transmission, excluding the involvement of mGluR2/3 subtypes at this developmental stage.     

Temporal response properties of lumbar-projecting vestibulospinal neurons to roll tilt in decerebrate cats

In decerebrate cats, rotation about the longitudinal axis of the animal, leading to sinusoidal stimulation of labyrinth receptors, produces a tonic contraction of limb extensors during side-down tilt ( responses) and of dorsal neck extensors during side-up tilt ( responses). These changes in posture are mediated, at least in part, by lateral vestibular nucleus (LVN) neurons, with response characteristics to stimulation of macular and/or canal receptors that have so far been evaluated at the level of either unidentified vestibulospinal (VS) neurons or vestibulo-collic neurons projecting to the upper cervical cord. In the present study we investigated the dynamics of the responses of VS neurons projecting to the lumbosacral segments of the spinal cord to increasing frequencies of tilt (from 0.026 to 0.32 Hz, ±10°). All the recorded units showed an average phase lead with respect to position of +25.6±5.5° (SE) at the tilt frequency of 0.026 Hz. Most of these neurons (n=32) were particularly activated during side-down tilt ( responses) and showed either a stable phase or an increase in phase lead of the responses with increasing frequency of tilt. At the tilt frequency of 0.026 Hz, the smaller the phase lead of the responses, the larger was the response gain. Moreover, the smaller the phase lead of the responses at that frequency of tilt, the smaller the increase in gain but the larger was the increase in lead of the responses obtained by increasing the stimulation frequency up to 0.32 Hz. Through this set of finely organized changes in unit response characteristics, the overall output of this population of neurons increased, while the phase angle of the responses reached the mean value of +64.9±2.6° (SE), thus becoming more related to the velocity than to the positional signal. The remaining units (n=7), which were mainly activated during side-up tilt ( responses), displayed an increase in phase lag of the responses to increasing frequency of stimulation, which reached the mean value of-118.9±14.5° (SE) at 0.32 Hz. The differences in the dynamic properties of these VS neurons projecting to the lumbosacral cord, with respect to those of previously recorded populations of VS neurons, are discussed.     

Chronic morphine treatment alters endogenous opioid control of hippocampal mossy fiber synaptic transmission

Synaptic adaptations are thought to be an important component of the consequences of drug abuse. One such adaptation is an up-regulation of adenylyl cyclase that has been shown to increase transmitter release at several inhibitory synapses. In this study the effects of chronic morphine treatment were studied on mossy fiber synapses in the guinea pig hippocampus using extracellular field potential recordings. This opioid-sensitive synapse was chosen because of the known role of the adenylyl cyclase cascade in the regulation of glutamate release. Long-term potentiation (LTP) at the mossy fiber synapse was enhanced after chronic morphine treatment. In control animals, opioid antagonists increased LTP but had no effect in morphine-treated guinea pigs. In contrast, the long-lasting depression of transmission induced by a mGluR agonist and CA1 LTP were not altered. Chronic morphine treatment neither caused tolerance to mu- and kappa-receptor-mediated inhibition at the mossy fiber synapse nor modified total hippocampal dynorphin levels. The results suggest that the phasic inhibition of glutamate transmission mediated by endogenous opioids is reduced after chronic exposure to morphine.