Adherence to Mediterranean diet and intake of antioxidants influence spontaneous conversion of atrial fibrillation.

BACKGROUND AND AIM: The Mediterranean diet (MedD) has long been associated with lower incidence of cardiovascular disease. Little information is available on association between MedD, vitamins intake and arrhythmias. We sought to investigate the relationship between adherence to MedD, antioxidants intake and spontaneous conversion of atrial fibrillation (AF). METHODS AND RESULTS: A group of 800 subjects was included in a case-control study; 400 of them had a first detected episode of AF. Nutritional parameters were assessed by a self-administered food frequency validated questionnaire and completed by an interviewer-administered 7 days diet recall. Adherence to MedD was evaluated using the Mediterranean Score and intake of antioxidants from food was calculated. Adherence to the Med Diet was lower in patients that developed AF compared to control (mean Med Score: 22.3 ± 3.1 vs 27.9 ± 5.6; p < 0.001). The median value was 23.5 (Q1-Q3 range 23-30) in patients with AF and 27.4 (Q1-Q3 range 26-33). The estimated intake of total antioxidants was lower in patients with AF (13.5 ± 8.3 vs 18.2 ± 9.4 mmol/d; p < 0.001). Patients in the highest quartile of Mediterranean Score had higher probability of spontaneous conversion of atrial fibrillation (OR1.9; 95%CI 1.58-2.81). High levels of antioxidants intake were also associated with an increasing probability of spontaneous conversion of arrhythmia (O.R. 1.8; 95%CI 1.56-2.99; P < 0.01). CONCLUSIONS: Patients with atrial fibrillation had lower adherence to MedD and lower antioxidant intake compared to control population. Moreover patients with arrhythmia showing a higher Med Score had more probability of a spontaneous conversion of atrial fibrillation.

Influence of coffee and caffeine consumption on atrial fibrillation in hypertensive patients.

BACKGROUND AND AIMS: Coffee and caffeine are widely consumed in Western countries. Little information is available on the influence of coffee and caffeine consumption on atrial fibrillation (AF) in hypertensive patients. We sought to investigate the relationship between coffee consumption and atrial fibrillation with regard to spontaneous conversion of arrhythmia. METHODS AND RESULTS: A group of 600 patients presenting with a first known episode of AF was investigated, and we identified 247 hypertensive patients. The prevalence of nutritional parameters was assessed with a food frequency questionnaire. Coffee and caffeine intake were specifically estimated. Left ventricular hypertrophy was evaluated by electrocardiogram (ECG) and echocardiogram. Coffee consumption was higher in normotensive patients. High coffee consumers were more frequent in normotensive patients compared with hypertensive patients. On the other hand, the intake of caffeine was similar in hypertensive and normotensive patients, owing to a higher intake in hypertensive patients from sources other than coffee. Within normotensive patients, we report that non-habitual and low coffee consumers showed the highest probability of spontaneous conversion (OR 1.93 95%CI 0.88-3.23; p=0.001), whereas, within hypertensive patients, moderate but not high coffee consumers had the lowest probability of spontaneous conversion (OR 1.13 95%CI 0.67-1.99; p=0.05). CONCLUSION: Coffee and caffeine consumption influence spontaneous conversion of atrial fibrillation. Normotensive non-habitual coffee consumers are more likely to convert arrhythmia within 48h from the onset of symptoms. Hypertensive patients showed a U-shaped relationship between coffee consumption and spontaneous conversion of AF, moderate coffee consumers were less likely to show spontaneous conversion of arrhythmia. Patients with left ventricular hypertrophy showed a reduced rate of spontaneous conversion of arrhythmia.

Spectrum of F8 gene mutations in haemophilia A patients from a region of Italy: identification of 23 new mutations.

SUMMARY: Haemophilia A (HA) is an X-linked recessive bleeding disorder caused by a lack or decrease of coagulation factor VIII activity. The molecular diagnosis of HA is challenging and a variety of different mutations have been identified throughout the F8 gene. Our aim was to detect the causative mutation in 266 HA patients from Emilia-Romagna region (Italy) and in all suspected carriers. Molecular analysis of F8 in 201 HA patients (152 index cases) was performed with a combination of several indirect and direct molecular approaches, such as long distance polymerase chain reaction, multiplex ligation-dependent probe amplification, denaturing high performance liquid chromatography and direct sequencing. The analysis revealed 78 different mutations, 23 of which were novel, not having been reported in national or international databases. The detection rate was 100%, 86% and 89% in patients with severe, moderate and mild HA, respectively. The information provided by this registry will be helpful for monitoring the treatment of HA patients in Emilia-Romagna and also for reliable genetic counselling of affected families in the future.

Antithrombin plasma levels decrease is associated with preeclampsia worsening.

Antithrombin plasma levels (AT) have been found decreased in women with preeclampsia (PE), but little is known about the trend of AT during the course of this disease. We prospectively investigated AT in consecutive women admitted to our hospital with a diagnosis of PE, to assess if AT fluctuations could be associated with the evolution of the disease. AT, platelet count and D-dimer levels were determined every other day. In the 73 patients studied, AT, platelet count and fibrinogen progressively reduced during the observational period, reaching a nadir on the day of delivery, whereas D-dimer progressively increased over time. Statistical analysis was restricted to the 39 women that had an AT measurement performed on each of days -1, 0 and +1, with respect to the day of delivery. These subjects showed a significant decrease in AT on the day of delivery compared to the day just before (77.8 +/- 15.1%vs. 85.4 +/- 14.2%, P = 0.027), followed by a recovery on the first day after delivery (87.6 +/- 21.3% from 77.8 +/- 15.1%, P = 0.005). Our study demonstrates that a significant drop in AT levels is associated with the clinical worsening of PE, regardless of its severity.

Intracerebral haemorrhage: an often neglected medical emergency.

Intracerebral haemorrhage (ICH) is the deadliest form of stroke, carrying a mortality rate between 30% and 55%, increasing to 67% in patients on oral anticoagulant therapy (OAT). Despite its relevant incidence, the treatment of ICH has been until recently a largely neglected item, addressed by only a few trials. Early treatment of ICH in non-anticoagulated patients with recombinant activated factor VII (rFVII) has been demonstrated to be able to limit the growth of the haematoma, but such a promising result requires further confirmations. In ICH patients receiving OAT a prompt reversal of the anticoagulant effect should be warranted in order to reduce the consequences of this dreadful adverse event. In clinical practice, however, just a small proportion of anticoagulated patients receive this treatment, probably because of the fear of thromboembolic complications. It is now time to check our way of thinking about ICH, regarding and treating it as a compelling medical emergency.

Pathophysiology of bleeding in surgery.

Bleeding is a major surgical complication. Although mortality rates of 0.1% are observed for surgical procedures, it may be 5% to 8% for elective vascular surgery, and increase to 20% in the presence of severe bleeding. In major surgery for liver diseases, as well as in cardiac surgery, excessive blood loss is associated with increased mortality, morbidity, and intensive care stay. Approximately 75% to 90% of intraoperative and early postoperative bleeding is due to technical factors. However, in some cases either acquired or congenital coagulopathies may favor, if not directly cause, surgical hemorrhage. Uncontrolled bleeding leads to a combination of hemodilution, hypothermia, consumption of clotting factors, and acidosis, which in turn worsen the clotting process, further exacerbating the problem in a vicious bloody circle. At present, the standard treatment for surgical bleeding is the rapid control of the source of bleeding by either surgical or radiological techniques. Blood-derived products as well as hemostatic agents, such as aprotinin, tranexamic acid, and DDAVP, are widely used to improve hemostatic balance in bleeding patients. Recombinant activated factor VII (rFVIIa) has been reported to be effective for the treatment of surgical or traumatic massive bleeding unresponsive to conventional therapy. Although most reports are anecdotal, and therefore exposed to a "positive" selection bias, the number of cases is impressive, strongly suggesting that in such patients rFVIIa may afford a hemostatic advantage beyond that of conventional replacement therapy.

Subunit and region-specific decreases in nicotinic acetylcholine receptor mRNA in the aged rat brain.

We have investigated possible changes in the mRNA levels for several alpha and beta subunits of the nicotinic acetylcholine receptor (nAChR) and the level of binding for nicotinic ligands in 7- to 32-month-old rats. Alpha4 and beta2, and to a lesser extent alpha6 and beta3, mRNA levels showed decreases between 20 and 30% at 29 months of age which in some areas reached 50% at 32 months of age. Alpha7 showed a small increase from 7 to 14 months and then a progressive decrease from 14 to 32 months down to the 7-month levels. 3H-epibatidine binding did not significantly change from 7 to 32 months of age in rat tel- and diencephalon. Binding in the substantia nigra was exceptional in that it showed a significant decrease starting from 23 months of age. 125I-alpha-bungarotoxin binding showed a pattern of change which roughly paralleled that of alpha7 mRNA. These findings show that an alteration in some steps of nAChR biosynthesis takes place during aging, which may be related to functional changes in nicotinic transmission.

[Recurrent subacute encephalopathy in the framework of idiopathic hypereosinophilic syndrome]. / Subakute rekurrierende Enzephalopathie im Rahmen eines idiopathischen hypereosinophilen Syndroms.

HISTORY: An 81-year-old man, previously good health, suddenly developed confusion and rapidly progressive severe tetraparesis. INVESTIGATIONS: Peripheral blood and bone marrow revealed marked eosinophilia: allergic, parasitic, neoplastic or vasculitic causes were excluded. Magnetic resonance imaging demonstrated multiple lesions in the cortical and subcortical white matter. DIAGNOSIS, TREATMENT AND COURSE: The findings indicated idiopathic hypereosinophilic syndrome involving the central nervous system and treatment with high doses of glucocorticoids was started. After a stormy course almost complete recovery occurred. CONCLUSION: Idiopathic hypereosinophilic syndrome can rarely manifest itself a an isolated severe subacute encephalopathy.

Spiral computed tomography: a novel diagnostic approach for investigation of the extracranial cerebral arteries and its complementary role in duplex ultrasonography.

BACKGROUND: For the detection of atherosclerotic lesions of the extracranial cerebral arteries, duplex ultrasonography (US) is an established operator-dependent method, whereas arteriography is associated with the not-insignificant risk of embolic complications. Spiral CT is a promising novel diagnostic tool that allows noninvasive, operator-independent diagnosis of obstruction of extracranial cerebral arteries. The aim of our prospective study was to evaluate in a clinical setting the complementary role of duplex US and spiral CT. METHODS AND RESULTS: We compared the results obtained independently by spiral CT and duplex US in 59 consecutive patients with clinical suspicion of an obstructive lesion affecting the carotid arteries. We analyzed a total of 354 segments from the extracranial carotid arteries, including the common, internal, and external carotid arteries. A total of 4 complete occlusions, 38 severe stenoses (70% to 99%), and 32 moderate stenoses (30% to 69%) were concordantly identified by means of duplex US and spiral CT. In 5 cases in which duplex US did not allow sufficient evaluation of the carotid artery because of a poor US window or severe calcification, spiral CT allowed identification and correct measurement of the stenotic lesion. The comparison of the percentage of stenosis with both methods was good (r=0.91, P=0.024). CONCLUSIONS: Our results indicate that spiral CT of the extracranial cerebral arteries is a promising noninvasive complementary and non-operator-dependent examination. Its application is particularly attractive in cases in which duplex US is not reliable (ie, severe kinking, severe calcification, short neck, and high bifurcation) and particularly when an overall view of the vascular field is required.

Hypothalamic neuropeptide Y and galanin in overweight rats fed a cafeteria diet.

We evaluated neuropeptide Y (NPY) and galanin (GAL) immunoreactivity (IR) and mRNA in the paraventricular and arcuate nucleus, respectively, in rats that became overweight (Ov) or not (NOv) when fed a cafeteria diet. After 2 months of diet, NOv rats showed a significant increase in NPY IR, whereas Ov rats showed a significant increase in GAL mRNA levels. None of these changes was present in rats overfed for 6.5 months. These differential changes in hypothalamic GAL and NPY transmissions may contribute to the different susceptibility of the two rat subpopulations to the weight-promoting effects of the hypercaloric diet.

Spermidine/spermine N1-acetyltransferase mRNA levels show marked and region-specific changes in the early phase after transient forebrain ischemia.

Considerable evidence points to an involvement of natural polyamines (putrescine, spermidine and spermine) in trophic regulation of brain tissue. Spermidine/spermine N1-acetyltransferase is the key enzyme in the interconversion pathway which leads to the formation of spermidine and putrescine from spermine and spermidine, respectively. In the present paper we have studied using in situ hybridization histochemistry the levels of spermidine/spermine N1-acetyltransferase mRNA in the rat central nervous system after transient forebrain ischemia. In the first hours after the insult, a modest increase in spermidine/spermine N1-acetyltransferase mRNA levels was observed in ependymal cells and other non-neuronal cells of all telencephalic and diencephalic regions. In addition, major increases in spermidine/spermine N1-acetyltransferase mRNA levels were observed in regions selectively vulnerable to the ischemic insult, such as striatum, hippocampus and cerebral cortex, during the first day post-reperfusion. The time course and extent of labelling increase were subregion- and cell-specific. At the cellular level, the labelling appeared markedly increased in neurons (8-10 fold in ventromedial striatum and CA1 region) and, to a lesser extent, in non-neuronal cells. The increase in SSAT mRNA levels was not directly related to cell degeneration, as it was detected in both some vulnerable and some resistant cell populations. However, the peak increase of SSAT labelling was precocious in resistant neurons (such as those of ventromedial striatum and dentate gyrus granular layer) and delayed or very limited in vulnerable neurons (such as those of CA1 pyramidal layer and dorsolateral striatum). The increase in spermidine/spermine N1-acetyltransferase may contribute to the increase in putrescine and decrease in spermidine levels observed after ischemia and gives further support to the notion that polyamine metabolism in the early phase after lesion is oriented towards putrescine production. This phenomenon could be relevant in determining the prevalence of neurotrophic vs. neurotoxic effects of polyamines.

Regional and cellular distribution of spermidine/spermine N1-acetyltransferase (SSAT) mRNA in the rat central nervous system.

Spermidine/spermine N1-acetyltransferase (SSAT) is the key enzyme responsible for polyamine interconversion. SSAT mRNA (visualized by in situ hybridization histochemistry) was shown to have a wide but heterogeneous distribution in the central nervous system (CNS) at both regional and cellular levels. The highest labelling was observed in hippocampus (pyramidal and polymorph neurons) and olfactory bulb. Present data suggest that polyamine metabolism in the CNS is not homogeneous but rather that the preferential production of a polyamine species is region- and cell type-specific.

[Myasthenia-like syndromes: current and future treatments]. / Syndromes myasthéniformes: traitements actuels et futurs.

Therapeutical aspects of disorders of the neuromuscular transmission are based on differential diagnosis between pre- or post-synaptically localized abnormalities of the neuromuscular junction, recognition of acquired and congenital forms and search for associated diseases and tumors, on prescription of drugs improving the transmission of acetylcholine and immunosuppressive agents, and on regular and quantified follow-up. In this clinical and therapeutic review, the two most common forms, myasthenia gravis and the Lambert-Eaton myasthenic syndrome, are discussed in the light of the 44 patients recently seen in our department.

[Neuritis of multiple cranial nerves in idiopathic focal pachymeningitis]. / Multinévrite crânienne dans le cadre d'une pachyméningite focale idiopathique.

A 76 years old patient suffering from insulin dependent diabetes presents a multiple, bilateral and asymmetric cranial neuropathy involving on the left side the cranial nerves VIII, IX with a participation of the efferent autonomic fibers of the nerves VII and IX (xerostomia) and the nerve XII, and involving on both sides the nerves VII and X. Like it is known from literature the nerve XI was spared, probably because of the more caudal emergence from the brainstem. The disease was preceded by a violent otalgia on the left side which was initially interpretated as a malignant external otitis. This affection was associated with an inflammatory syndrome that was easily monitored by the blood sedimentation rate. The course was favorable but marked by fluctuations of the neurological deficits. The MRI shows a pachymeningitis localised at the beginning in the medial fossa and on the cerebellar tentorium, later on the left parieto-occipital convexity. The diagnosis of a focal idiopathic pachymeningitis was confirmed by excluding different other affections like inflammatory, tumoral and infectious diseases, by using MRI examinations, CSF analysis and especially meningeal biopsy. It is a rare inflammatory disease of unknown origin with potentially persistent neurological deficits. We discuss the differential diagnosis and the therapeutical possibilities, which consist in a long term immunosuppression with corticosteroids and azathioprine.

A new missense mutation (Cys297-->Phe) of the low density lipoprotein receptor in Italian patients with familial hypercholesterolemia (FHTrieste).

During a survey of the mutations of the low density lipoprotein receptor (LDL-R) gene in Italian patients with familial hypercholesterolemia (FH), we identified a novel point mutation, that creates a new EcoRI site at the 5' end of exon 7, in a heterozygous FH subject (FH-100). The sequence of a cDNA fragment encompassing exon 7 showed the presence of a G-->T transversion in codon 297; this created a new EcoRI site and produced a missense mutation, leading to a Cys297-->Phe substitution in repeat A of the epidermal growth factor (EGF) precursor homology domain of LDL-R. Since the substitution of Cys297 disrupts the intracellular transport of the LDL-R protein, as previously demonstrated by site-directed mutagenesis, we suggest that this mutation is the cause of FH in the FH-100 proband. We screened the DNA of 303 Italian FH patients by amplification of exon 7 from genomic DNA followed by digestion with EcoRI or by Southern blotting. Two individuals (FH-64 and FH-127) were found to be carriers of the Cys297-->Phe mutation. Restriction fragment length polymorphism analysis demonstrated that, in two kindreds (FH-64 and FH-100), the haplotype in linkage with the Cys297-->Phe mutation was the same, suggesting the presence of a common ancestor. The Cys297-->Phe mutation has been designated FHTrieste after the name of the city in Northern Italy from which probands FH-100 and FH-127 originate.

Isolated complete orbital infarction: a common carotid artery occlusion syndrome.

When blood flow through the internal and external carotid arteries is completely interrupted by ipsilateral common carotid artery occlusion, the arterial orbital circulation may be more compromised than the brain supply. We studied a pure and extreme example of this situation in a patient who presented with acute orbital infarction, but no cerebral ischemia on clinical, CT and single-photon emission computerized tomography (SPECT) grounds. Ipsilateral blindness corresponded to retinal, choroidal and optic nerve infarction. The pattern of ophthalmoplegia, with relative sparing of adduction, was more compatible with a muscle than a nerve dysfunction, but a reactive dilated pupil, corneal anesthesia, and orbital pain suggested that the intraorbital branches of the ocular motor nerves and ophthalmic division of the trigeminal nerve were not spared. In addition, signs of widespread ocular ischemia were present. Sequential examinations documented the evolution pattern over 1 year. The absence of an orbital collateral supply from the contralateral external carotid and muscular cervical arteries systems, which contrasted with an adequate middle cerebral artery supply via the contralateral internal carotid artery, may explain this isolated and complete form of orbital ischemia due to common carotid artery occlusion.

[Hematoma of the head of the caudate nucleus]. / Hématomes limités à la tête du noyau caudé.

We studied five patients with cerebral hemorrhage limited to the head of the caudate nucleus. This rare localization represents 11% of central nuclei hemorrhages. This entity has various clinical expressions; some are similar to a subarachnoid hemorrhage, others show the same manifestations associated with hemiparesis and neuropsychological findings, while still in others, the neuropsychological syndrome with speech, behaviour or memory disturbances predominates. Recovery depends on the patient's previous clinical status and on the presence of associated lesions at the time of hemorrhage. Typical warning signs, like headache, are often absent in the elderly and debilitated. Meningismus is explained by the intraventricular extension of the hemorrhage. Motor deficit, usually moderate, is probably due to impairment of the anterior portion of the posterior arm of the internal capsule. Destruction of the head of the left caudate nucleus, which is part of the circuit causing "subcortical aphasias", is responsible for non specific speech disturbances, that are however remarkably rich in semantic paraphasias. These dysfunctions could be caused by a "cortical diaschisis" as suggested by SPECT analysis. Memory dysfunction as a result of caudate lesion is questioned. However confusion and behavioural disturbances, like preservations, transitory mutism and self neglect, seem characteristic. As shown by cerebral blood flow (CBF) studies, these disturbances might represent a frontal dysfunction caused by the interruption of the dorso-latero-prefrontal and orbito-frontal circuits. When the hemorrhage extends beyond the head of the caudate nucleus, behavioural changes occur due to the involvement of neighbouring structures such as the thalamus, internal capsule, temporal lobe and nucleus accumbens. Caudate hemorrhages occur mostly in the elderly, often with long-standing arterial hypertension causing lesions of the lenticulo-striate arteries. Severe stenosis or complete occlusion of the middle cerebral artery with a fragile anastomotic circuit or angiopathies in younger individuals (particularly Asiatics: moyamoya disease) are less frequent, but they should be considered and investigated by arteriography. Vascular malformations are a rare cause and a relationship with amyloid angiopathy can only be suspected.