Connectivity measures suggest a sub-cortical generator of myoclonus in Angelman syndrome

ObjectiveThe clinical and neurophysiological characteristics of myoclonus in Angelman syndrome (AS) have been evaluated in single case or small cohorts, with contrasting results. We evaluated the features of myoclonus in a wide cohort of AS patients.MethodsWe performed polygraphic EEG-EMG recording in 24 patients with genetically confirmed AS and myoclonus. Neurophysiological investigations included jerk-locked back-averaging (JLBA), cortico-muscular coherence (CMC) and generalised partial directed coherence (GPDC). CMC and GPDC analyses were compared to those obtained from 10 healthy controls (HC).ResultsTwenty-four patients (aged 3–35 years, median 20) were evaluated. Sequences of quasi-continuous rhythmic jerks mostly occurred at alpha frequency or just below (mean 8.4 ± 1.4 Hz), without EEG correlate. JLBA did not show any clear transient preceding the jerks. CMC showed bilateral over-threshold CMC in alpha band that was prominent on the contralateral hemisphere in the patient group as compared to HC group. GPDC showed a significantly higher alpha outflow from both hemispheres toward activated muscles in the patient group, and a significantly higher beta outflow from contralateral hemisphere in the HC group.ConclusionsThese neurophysiological findings suggest a subcortical generator of myoclonus in AS.SignificanceMyoclonus in AS has not a cortical origin as previously hypothesised.     

Evaluation of vilazodone for the treatment of depressive and anxiety disorders

Introduction: Major Depressive Disorder (MDD) and General Anxiety Disorder (GAD) significantly contribute to the global burden of disease. Vilazodone, a combined serotonin reuptake inhibitor and 5-HT1A partial agonist, is an approved therapy for the treatment of MDD and which has been further investigated for GAD.

Areas covered: This article covers the pharmacokinetics and pharmacodynamics of vilazodone and provides an evaluation of the clinical usefulness of vilazodone for the treatment of MDD and anxiety disorders. A literature search was performed using PubMed/MEDLINE, Web of Science and the Cochrane Library.

Expert opinion: Studies have shown that vilazodone is significantly superior to placebo. However, vilazodone cannot as yet be recommended as a first-line treatment option for MDD as it is unclear whether the drug’s dual mechanism of action provides greater efficacy than prevailing treatment options. Moreover, more phase IV studies are needed to establish its efficacy and long-term safety in larger and more diverse populations. Although vilazodone may have an additional advantage for the treatment of anxiety symptoms in MDD, here also additional studies are required to confirm its efficacy over and above SSRI alternatives and other antidepressant treatments. Therefore, presently, vilazodone should be considered as a second- or third-line treatment option for MDD and GAD.     

Nonconvulsive Status Epilepticus: High Incidence of Complex Partial Status

Nonconvulsive status epilepticus may be subdivided into generalized (absence) status and complex partial status. The latter is regarded as a rarity, whereas the former constitutes the dominant part of the hitherto reported cases. We report 10 consecutive cases of adult patients with nonconvulsive status epilepticus, all documented by ictal electroencephalographic (EEG) recordings. Five had a complex partial status; the origin of the complex partial status appeared to be frontal in four of these patients. Three had recurrent complex partial seizures with incomplete recovery between seizures, and two had more continuous symptoms. One of the latter exhibited neither motor phenomena nor automatisms. The effect of diazepam or clonazepam was immediate in all 10 cases though transient in eight. A lasting control of the status was not achieved in six patients until i.v. phenytoin was added. The difficulties in the differentiation between complex partial status and absence status despite ictal EEG recordings are discussed, illustrated by a case with seizure discharges of a focal onset which rapidly generalized. The study indicates that complex partial status may be more common and the clinical expressions of absence status more variable than hitherto recognized.     

Influence of moderate hypothermia on cerebral oxygenation in pigs with intracranial hypertension

BACKGROUND: Moderate hypothermia is one of the effective therapeutic methods for head injury in recent years, there are many mechanisms of moderate hypothermia for brain protection, and its influence on cerebral oxygenation is also one of them. OBJECTIVE: To observe the influence of moderate hypothermia on cerebral oxygenation of animals with acute intracranial hypertension, and further investigate the protective mechanism of moderate hypothermia. DESIGN: A randomized controlled trial. SETTING: Department of Neurosurgery, Renji Hospital affiliated to the Medical College of Shanghai Jiao Tong University. MATERIALS: Twenty healthy little pigs, either male or female, weighing 4.5–5.5 kg, were used. Neurotrend-typed multiparameter monitoring system (Diametrics Company, British); CMA/100 micro-injection pump (Carnegie Company, Sweden). METHODS: The experiment was conducted in the Changzheng Hospital affiliated to the Second Military Medical University of Chinese PLA in November, 2001. The pigs were randomized into two groups: the normothermia group (control group, n =10) and moderate hypothermia group (n =10). ① Bilateral femoral arteries were separated, one was connected to pressometer for monitoring mean arterial pressure (MEP), and the other for analysis of blood gases [including peripheral blood pH value, arterial partial pressure of carbon dioxide (PaCO2), arterial partial pressure of carbon dioxide (PaCO2), HCO3–]. ② Rectal temperature was monitored with mercurial thermometer. ③ Intracranial pressure was monitored using Camino optic ICP probe placed in the subdural space. ④ Neurotrend multiparameter monitoring sensor was inserted into the white matter for about 4 cm to determine cerebral perfusion pressure (CPP, CPP=MAP(ICP), brain tissue partial oxygen pressure (PO2), partial pressure of carbon dioxide (PCO2), HCO3– and brain temperature. The rectal temperature of animals in the moderate hypothermia group was lowered to 34 ℃ using ice bags, and the body temperature was maintained at 33–35 ℃ for 2 hours. The changes of the parameters were observed continuously, and the pigs in the normothermia group were not treated with cooling. MAIN OUTCOME MEASURES: ① MAP, ICP, rectal temperature, CCP; Indexes of cerebral oxygenation detected with Neurotrend-typed multiparameter monitoring system; ② Results of blood gases analysis in the moderate hypothermia group. RESULTS: All the 20 pigs were involved in the analysis of results. ① MAP, ICP, rectal temperature, CCP and indexes of cerebral oxygenation: In the moderate hypothermia group, the ICP after cooling was obviously lower than that before cooling [(3.31±1.19), (5.33±0.95) kPa, P < 0.05], CCP was higher, brain tissue PCO2 [(12.03±1.73), (10.59±2.01) kPa, P < 0.05], and brain tissue pH value was higher [(7.03±1.63), (9.40±1.30) kPa, P < 0.05], whereas the brain temperature was decreased as compared with that before cooling [(34.9±0.3), (37.2±0.2) ℃, P < 0.05]. ② Results of blood gases analysis in the moderate hypothermia group: There were no significant differences in the parameters of peripheral arterial blood gases analysis before and after cooling in the moderate hypothermia group (P > 0.05) CONCLUSION: Moderate hypothermia will not impair the cerebral oxygenation, and it can reduce brain tissue CO2 and decrease brain tissue acidosis.     

对诊断PADAM的游离睾酮指数的评估

目的 评价诊断中老年男子部分雄激素缺乏综合征（PADAM）的游离睾酮指数（FTI）.方法 对129例45岁以上健康男性的FTI进行年龄相关分析.以推算的游离睾酮（CFT）值为依据,对FTI进行有效性检验.结果 男子在中老年期FTI与增龄呈明显的负相关.FTI敏感性97.78%,特异性58.33%.结论 计算简单的FTI可用于PADAM病人的筛选和随访,尤其对70岁以上男子是血清FT较为有效的参数.     

Development of a Device for Removing a Partial Denture in a Patient with Scleroderma

Scleroderma is a chronic disease that has been associated with immune dysfunction. One of the oral manifestations is microsomia, a result of collagen deposition in the perioral tissues. The complexity of treating these patients includes limited mouth opening ability, and difficulty inserting and removing dentures due to finger deformity. This article will describe an appliance specially designed especially for scleroderma patients, which facilitates treatment of the patient with removable partial dentures (RPD).     

Malodour in denture wearers: an ill-defined problem

Denture plaque has not been studied to the same extent as dental plaque, and although there are many similarities in microbial composition, there are some significant differences. Denture-induced stomatitis is associated with poor denture hygiene, a more acidogenic plaque and the presence of Candida albicans . Obligate Gram-negative anaerobic micro-organisms, although present in denture plaque, have rarely been specifically investigated. Opportunist pathogens including coliforms and staphylococci have been isolated from dentures. Teeth adjacent to partial dentures are more susceptible to caries and periodontal diseases, perhaps due to an increased plaque buildup at the prosthesis/tooth interface. Little work has been published on malodour associated with dentures. The inert material provides a substratum for the plaque biofilm, which encompasses a range of odour-producing species. The microbiology of the tongue in denture wearers has not been specifically studied. Thus the nature, origin and extent of malodour in denture wearers is ill-defined, but many species capable of producing malodorous compounds are present. The wide age and health range presented by denture wearers further confounds investigation. There is a need for further work in the area, both for cosmetic- and health-associated reasons in the increasing elderly population.     

Early Designs for the Occlusal Anatomy of Posterior Denture Teeth: Part III

Part III of this series of articles, like Part II, reviews the pioneering efforts in the 19th century to improve the quality of artificial teeth. The focus of this article, unlike that of Part II, is specifically modifications in the design of the occlusal anatomy of the 19th century denture teeth, along with the theories of mandibular movement that inspired those modifications. This article concludes the introductory phase of this project, which seeks to unravel the confusing history of the development of (posterior) denture teeth.     

Fluctuating PEEP (F–PEEP) versus conventional PEEP in dogs with asymmetrical lung injury

Fluctuating PEEP (F-PEEP) is a newly developed PEEP in which end-expiratory pressure (EEP) is periodically changed within a certain range. In a dog model with unilateral lung injury induced by the introduction of hydrochloric acid, F-PEEP in which the EEP was periodically changed from 0.5 to 1.5 kPa at periods of 6 min, and conventional PEEP (C-PEEP) with an optimized EEP of 1.0 kPa, were each applied for 30 min. F-PEEP produced a significantly greater improvement of PaO2 and intrapulmonary shunt (QS/QT) than C-PEEP, and at the low EEP phase, the greatest improvement accompanied by an increased dynamic compliance and a large cardiac output was obtained. These results suggest that F-PEEP provides a useful mode of artificial ventilation for the treatment of unilateral lung injury.     

Research review: DNA polymerases as molecular markers of the regenerating capacity of hepatocytes

Hepatocyte regeneration has been widely investigated, with the mitotic index and the incorporation of [³H]thymidine being used as regeneration markers. We focused on the induction of DNA replication enzymes, particularly DNA polymerases (pol) α, δ, and ε. Using rat models, we have shown that the activity of pol α in crude liver extract well represents the regenerating capacity of hepatocytes. Using pol α as an indicator, we analyzed liver regeneration in rat models under various conditions: obstructive jaundice, external or internal biliary drainage, and the obstruction of portal vein branches. It has been revealed that the ligation of the common bile duct alone induces a certain amount of hepatocyte proliferation. It was striking that external biliary drainage suppressed regeneration capacity in cholestatic rat liver after partial hepatectomy. The strong regeneration in nonligated lobes induced by portal branch ligation was similar to the liver regeneration seen after partial hepatectomy with respect to the induction of DNA polymerases. Taken together, the aspects of DNA replication, particularly the induction of DNA polymerases, may contribute to shedding new light on the regeneration of human liver. This work was supported in part by a Grant-in-Aid for General Scientific Research and for Cancer Research from the Ministry of Education, Science and Culture, Japan, and by grants from the Uehara Memorial Foundation