[Smith-Magenis syndrome is an association of behavioral and sleep/wake circadian rhythm disorders]. / Le syndrome de Smith-Magenis, une association unique de troubles du comportement et du cycle veille/sommeil.

Smith-Magenis syndrome (SMS) is a genetic disorder characterized by the association of facial dysmorphism, oral speech delay, as well as behavioral and sleep/wake circadian rhythm disorders. Most SMS cases (90%) are due to a 17p11.2 deletion encompassing the RAI1 gene; other cases stem from mutations of the RAI1 gene. Behavioral issues may include frequent outbursts, attention deficit/hyperactivity disorders, self-injuries with onychotillomania and polyembolokoilamania (insertion of objects into bodily orifices), etc. It is noteworthy that the longer the speech delay and the more severe the sleep disorders, the more severe the behavioral issues are. Typical sleep/wake circadian rhythm disorders associate excessive daytime sleepiness with nocturnal agitation. They are related to an inversion of the physiological melatonin secretion cycle. Yet, with an adapted therapeutic strategy, circadian rhythm disorders can radically improve. Usually an association of beta-blockers in the morning (stops daily melatonin secretion) and melatonin in the evening (mimics the evening deficient peak) is used. Once the sleep disorders are controlled, effective treatment of the remaining psychiatric features is needed. Unfortunately, as for many orphan diseases, objective guidelines have not been drawn up. However, efforts should be focused on improving communication skills. In the same vein, attention deficit/hyperactivity disorders, aggressiveness, and anxiety should be identified and specifically treated. This whole appropriate medical management is underpinned by the diagnosis of SMS. Diagnostic strategies include fluorescent in situ hybridization (FISH) or array comparative genomic hybridization (array CGH) when a microdeletion is sought and Sanger sequencing when a point mutation is suspected. Thus, the diagnosis of SMS can be made from a simple blood sample and should be questioned in subjects of any age presenting with an association of facial dysmorphism, speech delay with behavioral and sleep/wake circadian rhythm disorders, and other anomalies including short stature and mild dysmorphic features.

Adaptive dual-comb spectroscopy in the green region.

Dual-comb spectroscopy is extended to the visible spectral range with two short-pulse frequency-doubled free-running ytterbium-doped fiber lasers. When the spectrum is shifted to other domains by nonlinear frequency conversion, tracking the relative fluctuations of the femtosecond oscillators at their fundamental wavelength automatically produces the correction signal needed for the recording of distortion-free spectra. The dense rovibronic spectrum of iodine around 19,240 cm(-1) is recorded within 12 ms at Doppler-limited resolution.

[Imaging non motor signs in Parkinson's disease]. / Imagerie des signes non moteurs dans la maladie de Parkinson.

Parkinson's disease is mainly considered as a motor disorder defined by a motor triad. However, various non-motor manifestations may be encountered in Parkinson's disease, including hyposmia, pain, fatigue, sleep disorders, cognitive and behavioral disorders. The pathophysiology of these signs is complex, not univocal and remains poorly understood. Functional imaging techniques either by positron emission tomography, single photon emission tomography or functional magnetic resonance imaging provide an invaluable opportunity to better understand the pathophysiology of these signs. In this paper, we present a review of the recent advances provided by functional imaging in this area.

History of the 'geste antagoniste' sign in cervical dystonia.

The geste antagoniste is a voluntary maneuver that temporarily reduces the severity of dystonic posture or movements. It is a classical feature of focal and particularly cervical dystonia. However, the precise historical aspects of geste antagoniste still remain obscure. The goals of this review were (1) to clarify the origin of the geste antagoniste sign; (2) to identify the factors that led to its diffusion in the international literature; (3) to follow the evolution of that term across the twentieth century. We used medical and neurological French, German and English literature of the late nineteenth and early twentieth centuries, and the PubMed database by entering the terms geste antagoniste, antagonistic gesture and sensory trick. The geste antagoniste sign is a legacy of the Paris Neurological School of the end of the nineteenth century. The term was introduced by Meige and Feindel in their 1902 book on tics, written in the vein of their master, Brissaud, who first described this sign in 1893. The almost immediate translations of this book by Giese into German and Kinnier Wilson into English contributed to the rapid spreading of the term geste antagoniste, which is still in use worldwide today. The term antagonistic gesture is the translation proposed by Kinnier Wilson, which also led to the use of the term geste antagonistique. The geste antagoniste sign has long been considered a solid argument for the psychogenic origins of dystonia until the 1980s when Marsden made strong arguments for its organic nature.

Xeroderma pigmentosum: a rare cause of chorea.

Xeroderma pigmentosum (XP) is an uncommon inherited dermatological disorder characterized by a high degree of skin photosensitivity with development of carcinomas at an early age. Neurological manifestations may be encountered in XP but few detailed descriptions have been provided. Here we describe a sister and a brother presenting chorea, dystonia, myoclonus, ataxia and polyneuropathy related to XP.

[Behavioral disorders in Parkinson's disease: from pathophysiology to the mastery of dopaminergic treatment]. / Maladie de Parkinson: de la physiopathologie des troubles psychiques à la maîtrise du traitement dopaminergique.

INTRODUCTION: Behavioral changes in Parkinson's disease are complex and their pathophysiology is not yet fully understood. The dopaminergic system seems to play a major role and most of the behavioral disorders in Parkinson's disease can be classified into either hypodopaminergic if related to the disease itself or hyperdopaminergic if related to dopaminergic treatment. STATE OF THE ART: Subthalamic stimulation, which enables withdrawal of dopaminergic medication at an advanced stage in the disease, provides a model for the study of certain nonmotor, dopamine-sensitive symptoms. Such a study has shown that apathy, which is the most frequent behavioral problem in Parkinson's disease, is part of a much broader hypodopaminergic behavioral syndrome which also includes anxiety and depression. Nonmotor fluctuations--essential fluctuations in the patient's psychological state--are an expression of mesolimbic denervation, as shown in positron emission tomography. Drug-induced sensitization of the denervated mesolimbic system accounts for hyperdopaminergic behavioral problems that encompass impulse control disorders that can be alternatively classified as behavioral addictions. The association of impulse control disorders and addiction to the dopaminergic medication has been called dopamine dysregulation syndrome. While L-dopa is the most effective treatment for motor symptoms, dopamine agonists are more effective in improving the nonmotor levodopa-sensitive symptoms. On the other hand, L-dopa induces more motor complications and dopamine agonist more behavioral side effects. There is increasing data and awareness that patients' quality of life appears to be dictated by hypo- and hyperdopaminergic psychological symptoms stemming from mesolimbic denervation and dopaminergic treatment rather than by motor symptoms and motor complications related to nigrostriatal denervation and dopaminergic treatment. PERSPECTIVES: Better management requires knowledge of the clinical syndromes of hyper- and hypodopaminergic behaviors and nonmotor fluctuations, a better understanding of their underlying mechanisms and the development of new evaluation tools for these nonmotor symptoms. CONCLUSIONS: The neurologist who strives to gain mastery of dopaminergic treatment needs to fine tune the dosage of levodopa and dopamine agonists on an individual basis, depending on the presence of motor and nonmotor signs respectively.

Haplotype-dependent HLA susceptibility to nasopharyngeal carcinoma in a Southern Chinese population.

We have conducted a comprehensive case-control study of a nasopharyngeal carcinoma (NPC) population cohort from Guangxi Province of Southern China, a region with one of the highest NPC incidences on record. A total of 1407 individuals including NPC patients, healthy controls, and their adult children were examined for the human leukocyte antigen (HLA) association, which is so far the largest NPC cohort reported for such studies. Stratified analysis performed in this study clearly demonstrated that while NPC protection is associated with independent HLA alleles, most NPC susceptibility is strictly associated with HLA haplotypes. Our study also detected for the first time that A(*)0206, a unique A2 subtype to South and Southeast Asia is also associated with a high risk for NPC. HLA-A(*)0206, HLA-B(*)3802 alleles plus the A(*)0207-B(*)4601 and A(*)3303-B(*)5801 haplotypes conferred high risk for NPC showing a combined odds ratio (OR) of 2.6 (P<0.0001). HLA alleles that associate with low risk for NPC include HLA-A(*)1101, B(*)27, and B(*)55 with a combined OR of 0.42 (P<0.0001). The overall high frequency of NPC-susceptible HLA factors in the Guangxi population is likely to have contributed to the high-NPC incidence in this region.

[Chronic cough in childhood]. / Toux chronique de l'enfant.

INTRODUCTION: Although less frequent than viral induced recurrent cough; chronic cough remains a sometimes difficult to resolve diagnostic tool. STATE OF THE ART: Most authors estimate that a cough can by considered as chronic after three weeks of duration. Few papers have been published concerning etiologic diagnosis of chronic cough in childhood but these indicate the same main causes as in adults: cough variant asthma, postnasal drip syndrome, gastro-esophageal reflux. Nevertheless, each age bracket presents specific diagnosis: malformations between zero and one year, psychogenic cough in adolescents. PERSPECTIVES: New techniques as induced sputum studies helps to refine chronic cough diagnosis in childhood (after 7 years). Eosinophilic bronchitis, associated or not to bronchial hyperresponsiveness has important therapeutic consequences because associated with a favourable response to corticosteroids. Other techniques will be developed in the future (exhaled NO for example). CONCLUSIONS: Chronic cough in childhood must be investigated from an anatomic point of view and on frequency arguments. Control and removal of the cough will only be obtained if a precise diagnosis and a suitable treatment are reached.

[Rapid acquired tolerance to cow's milk by oral route in a case of severe childhood food allergy]. / Accoutumance rapide par voie orale au lait de vache dans un cas d'allergie alimentaire sévère chez l'enfant.

An attempt to desensitize to cow's milk a 5 year-old girl who had been forced to follow a strict egg and milk-free diet with concomitant impossibility of attendance at school, posed major practical problems. In a hospital environment, under cover of treatment with Nalcron and Solemedrol, the re-introduction of milk was started with 10(-10) ml of milk. After a severe episode on the 1st day, the child was able to take 100 ml on the 10th day and thereafter. Today, the child continues with Nalcron treatment, but she no longer has a diet and she leads a normal lifestyle.

[Pulmonary localization of Kaposi's sarcoma]. / Localisation pulmonaire d'un sarcome de Kaposi.

The authors describe a case of a 61 year old man suffering from Kaposi's sarcoma with pulmonary involvement associated with a hairy cell leukaemia. The numerous associations with Kaposi's sarcoma are reviewed and the circumstances of the unexpected appearance of this disease, placing it in the group of opportunistic diseases. The prognosis is totally different according to whether it is an isolated Kaposi's sarcoma without visceral localisation or to a form with polyvisceral involvement and associated with another neoplasm or immunodepression.

Metabolism of thymoxamine. II. Studies with 14C-thymoxamine in man.

Thymoxamine is rapidly and completely absorbed in man. Rapid biotransformation is observed after intravenous and oral administration of 40 mg 14C-thymoxamine HCl. No unchanged compound is found in the body. More than 90% of plasma and urine radioactivity could be ascribed to six metabolites: the desacetyl compound (metabolite I), the monodemethylated metabolite I (metabolite II), the sulfate conjugates of I and II (metabolites III and IV) and the glucuronides of I and II (metabolites V and VI). The unconjugated metabolites are observed in plasma only after intravenous administration. Similar patterns for polar metabolites are found in plasma and urine for both routes of administration. The sulfate fraction amounts to about 50-60% and the glucuronide fraction to about 30-40% of the radioactivity, the conjugates of metabolite I being more abundant than those of metabolite II. The elimination of the metabolites is rapid, the half-life of radioactivity elimination being 1.5 h during the first 12 hours and 12 h thereafter. 80% of the radioactivity dose is recovered in the urine within 4 hours. Recovery after four days amounts to 99.8% (i.v.) and 97.7% (oral). The results are discussed with regard to the application of the drug in man, taking into account that not only the unconjugated metabolites but also the sulfate conjugates are pharmacologically active.

Metabolism of thymoxamine. I. Studies with 14C-thymoxamine in rats.

Thymoxamine is rapidly and completely absorbed in rats. It is a prodrug which does not enter the systemic circulation in its unchanged form. After either oral or intravenous administration it undergoes rapid and intense metabolism involving four biotransformation reactions: Enzymatic hydrolysis to the corresponding phenol (metabolite I), Monodemethylation to metabolite II, Sulfate conjugation of I and II (metabolites III and IV) and Conjugation of I and II with glucuronic acid (metabolites V and VI). With these 6 metabolites identified approximately 95% of the radioactivity can be accounted for in plasma, urine and bile. Whereas the systemic availability of I and II is low, III and IV show high bioavailability. Metabolites I to IV are pharmacologically active, while III and IV are less potent than I and II. The radioactivity distribution in tissues is different after oral and intravenous administration consistent with the higher portion of unconjugated metabolites in the body after administration by parenteral route. Although 60% of the labelled compounds is eliminated via bile, the radioactive compounds are almost completely excreted in the urine after both routes of administration. This demonstrates complete reabsorption of the biliary metabolites. Secondary peaks of radioactivity in plasma and organs at 4 hours are explained by the participation of the metabolites in the enterohepatic circulation.

Clinical studies with terfenadine in seasonal allergic rhinitis in France.

The results of a multicentre investigation carried out on 312 pollinic patients are presented. Efficacy of alpha-[4-(1,1-dimethylethyl)phenyl]-4-(hydroxydiphenylmethyl)-1- piperidinebutanol (terfenadine, RMI 9918, Triludan, Teldane, resp.) has been estimated from a global appreciation and the evolution of 11 symptoms, and tolerance on the frequency of diurnal sleepiness. The results showed a very good efficacy of terfenadine and the absence of a depressant effect.

[Metabolism and pharmacokinetics of piprozoline in the rat, dog and man. 1. Studies with the radioactively-labeled substance]. / Metabolismus und Pharmakokinetik von Piprozolin bei Ratte, Hund und Mensch. 1. Mitteilung: Untersuchungen mit radioaktiv markierter Substanz

The new choleretic ethyl (Z-3-ethyl-4-oxo-5-piperidino-thiazolidin-2-ylidene) acetate (piprozoline, Gö 919, Probilin) is absorbed well and rapidly in rats, dogs and humans. Maximum 14C plasma concentrations are found 1-2 h after oral administration of the labelled substance to fasting animals and human volunteers. When administered to test persons after breakfast, the absorption is delayed but the absorbed amount is unaffected. Elimination of the radioactivity from the plasma occurs in two phases; 24 h after administration the radioactivity concentration has dropped to 5-8% of the maximum levels. Piprozoline is almost completely metabolized during absorption. The primary metabolic step is the enzymatic hydrolysis of the ester bond to the corresponding acid (metabolite I). At the time of maximum plasma concentration most of the plasma radioactivity corresponds to metabolite I, which also possesses choleretic activity. Approx. 65% of the radioactive dose is eliminated renally in all three species, approx. 60% being excreted within the first 24 h. Approx. 40-60% of the urinary radioactivity can be ascribed to metabolite I, both in its free form and conjugated with glucuronic acid. No unchanged substance is found in the urine. A comparison of the pharmacokinetic and metabolic behaviour of piprozoline in rats, dogs and humans showed that it was similar in all three species.

[ On the metabolism of ethyl-DL-trans-2-dimethylamino-1-phenyl-cyclohex-3-ene-trans-1-carboxylate-hydrochloride (Tilidine-HCl). 2nd Communication: Studies with 14C-labelled substance on rats and dogs]. / Zum Metabolismus von DL-trans-2-Dimethylamino-1-phenyl-cyclohex-3-en-trans-1-carbonsäureäthylester-hydrochlorid (Tilidin-HCl). 2. Mitteilung: Untersuchungen mit der radioaktiv markierten Substanz an Ratten und Hunden

Absorption, distribution, metabolism and excretion of the potent analgesic ethyl-DL-trans-2-timethylamino-1-phenyl-chclohex-3-ene-trans-1-carboxylate-hydrochloride (tilidine-HCl, Gö 1261 C, active ingredient of Vloron) were investigated in rats and dogs, using the radioactively labelled substance. Following oral administration, tilidine-HCl is rapidly and completely absorbed from the duodenum. During absorption, tilidine undergoes a marked first-pass effect. In plasma several metabolites are found, part of them occurring in higher concentrations than the unchanged substance. The metabolites are also formed rapidly after parenteral administration, unchanged tilidine being found in higher concentrations than any of the metabolites at all times measured. Following both routes of administration, the Met. I (nortilidine), also possessing a strong analgesic activity, reaches similar plasma levels. 14C distribution studies in rats showed a relatively high concentration of the radioactivity in the excretory organs, liver and kidneys. In brain, muscle tissue and blood much lower 14C concentrations are found. The concentrations measured in the foetal organs correspond to those in the muscle tissue of the mother animals and are, therefore, much lower than in most maternal organs. The radioactivity is eliminated from the foetal organs at the same rate as from the maternal organs. Tilidine is rapidly and completely eliminated with the excrements, nearly exclusively in the form of metabolic products. Rats eliminate 50% of the given radioactivity via the kidneys. The relatively high fecal elimination is based on the biliary metabolites. Following intraduodenal and intravenous administration to rats with an interrupted enterohepatic circulation, about 80% of the dose is eliminated with bile. The biliary metabolites are partly reabsorbed. In dogs, approx. 80% of the applied radioactivity is eliminated with urine.