Deep brain stimulation of anterior nucleus thalami disrupts sleep in epilepsy patients.

In view of the regulatory function of the thalamus in the sleep-wake cycle, the impact of deep brain stimulation (DBS) of the anterior nucleus thalami (ANT) on sleep was assessed in a small consecutive cohort of epilepsy patients with standardized polysomnography (PSG). In nine patients treated with ANT-DBS (voltage 5 V, frequency 145 Hz, cyclic mode), the number of arousals during stimulation and nonstimulation periods, neuropsychiatric symptoms (npS), and seizure frequency were determined. Electroclinical arousals were triggered in 14.0 to 67.0% (mean 42.4 ± SD 16.8%) of all deep brain stimuli. Six patients reported npS. Nocturnal DBS voltages were reduced in eight patients (one patient without npS refused) and PSGs were repeated. Electroclinical arousals occurred between 1.4 and 6.7 (mean 3.3 ± 1.7) times more frequently during stimulation periods compared to nonstimulation periods; the number of arousals positively correlated with the level of DBS voltage (range 1 V to 5 V) (Spearman's rank coefficient 0.53121; p < 0.05). No patient experienced seizure deterioration and four patients reported remission of npS. This case-cohort study provides evidence that ANT-DBS interrupts sleep in a voltage-dependent manner, thus putatively resulting in an increase of npS. Reduction of nocturnal DBS voltage seems to lead to improvement of npS without hampering efficacy of ANT-DBS.

Bi-level VNS therapy with different therapy modes at night and daytime improves seizures and quality of life in a patient with drug-resistant epilepsy.

Induction or aggravation of sleep apnea is a known side effect of vagus nerve stimulation (VNS). We report the case of a 44 year old male with drug-resistant epilepsy and depression who did not experience any seizure reduction after 1 year of VNS but a worsening of depression and daytime sleepiness. After confirming VNS-associated sleep apnea we started the first bi-level VNS therapy with standard VNS settings during daytime and reduced settings during nighttime. Anti-seizure medication remained unchanged. Within 12 months his seizure frequency was reduced by 90 % and his depression improved, permitting a cessation of his antidepressant medication. The observations made in this case have contributed to the manufacturer of VNS developing new generator models that can automatically provide bi-level VNS.

Complex sexual behaviors during sleep as a manifestation of epilepsy: a case series.

STUDY OBJECTIVES: Complex sexual behavior during sleep (CSBS) is a well described clinical entity in nonrapid eye movement (NREM) sleep parasomnias (i.e. sexsomnia). We report a retrospective case series of CSBS as clinical manifestation of epileptic seizures and compare them with the semiology of sexsomnia. METHODS: Video-electroencephalopraphy (EEG)-monitoring data of patients with epileptic and nonepileptic paroxysmal events from one tertiary epilepsy center between 2013 and 2016 were retrospectively reviewed. Clinical features and presurgical, electroclinical, and follow-up data are presented and then discussed in the context of other published cases. RESULTS: From 4,629 patients, 6 patients had CSBS. EEG, single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), and histopathology confirmed an epileptic origin in four female patients, with temporal or frontal seizures. Two male patients had sexsomnia. None of the epilepsy patients had parasomnias. Clinical criteria to differentiate epileptic from parasomnic CSBS were: events also occurred out of wakefulness; current presence of additional nonsexual manifestations of epilepsy; sexual behavior only as part of a broad spectrum of emotional and motor automatisms; stereotyped behavior pattern without modulability by bystanders; unarousability during the event; no completion of sexual intercourse. The accuracy of the clinical diagnosis was improved by the development of an algorithm comparing patients' fulfillment of the criteria of epilepsy versus parasomnia. CONCLUSIONS: In our cohort, CSBS was a rare ictal phenomenon in temporal or frontal seizures. Symptomatological similiarities with sexsomnia might be explained by the same phylogenetically primitive "central pattern generator" manifesting in ictal CSBS by activation and in sexsomnia by disinhibition. Ictal CSBS should be considered in the differential diagnosis of sexsomnia.

Quality improvement opportunities for handover practices in birth centres: A case study from a process perspective.

RATIONALE, AIMS AND OBJECTIVES: Handovers within and between health care settings are known to affect quality of care. Health care organizations, struggle how to guarantee best care during handovers. The aim of this paper is to evaluate handover practices in Dutch birth centres from a process perspective, to identify obstacles and opportunities for quality improvements. METHODS: This case study in 7 Dutch birth centres was undertaken from a process perspective by conducting observations and using process mapping. This study is part of the Dutch Birth Centre Study. RESULTS: Solutions to obstacles during handovers from a birth centre to a hospital were identified in at least 1 of the 7 birth centres. Four of the centres had agreements with a hospital for client support when a caregiver in a birth centre was absent. Face-to-face communication during handover was observed in 6 of the 7 centres. An electronic health record was noted in 1 centre; joint training of acute situations was available in 2 centres with 3 centres indicating that this was not compulsory. Continuity of caregiver was present in 4 birth centres with postpartum care available in 3 centres. CONCLUSIONS: Ensuring quality during handovers requires a case-specific process approach. This study reveals distinctive aspects during handovers, concrete obstacles, and potential solutions for quality improvements in inter-organizational networks, transferrable to birth centres in other countries as well.

Is patient flow more efficient in Urgent Care Collaborations?

OBJECTIVE: Emergency Departments and out-of-hours General Practitioner services collaborate increasingly in Urgent Care Collaborations (UCCs) by sharing one combined entrance and joint triage. The aim of this study is to examine the difference between UCCs and providers who operate separately with respect to the efficiency of patient flow. METHODS: This study had a cross-sectional observational design comparing three regions with UCC with three regions with usual care. Outcome measures were efficiency of patient flow, defined as a reducing length of stay (LOS), waiting time (WT) and the mean number of handovers. Data were obtained from electronic medical records. RESULTS: LOS (median 34:00 vs. 38:52 min) and WT (median 14:00 vs. 18:43 min) were statistically significantly longer in UCCs compared with usual care. This difference is mainly explained by the prolonged LOS and WT for consulting a General Practitioner. The mean number of interunit handovers was larger in UCCs. CONCLUSION: The results indicate that, on average, UCCs do not enhance the efficiency of patient flow. The median LOS and WT are longer in UCCs and more handovers occur in UCCs compared with usual care.

Characterization of beta-adrenoceptor subtypes in rat kidney with new highly selective beta 1 blockers and their role in renin release.

Highly selective beta-adrenoceptor blocking agents with a beta 1: beta 2-selectivity ratio of 0.015 to 3400 were used to characterize the beta-adrenoceptors present in rat kidney and to identify those mediating renin release. The results obtained with ICYP binding to kidney membranes revealed the presence of both beta 1- and beta 2-adrenoceptors in a ratio of 1:1. The pKD beta 1- and pKD beta 2-values of selective beta-antagonists obtained in rat kidney membranes correlated well with those found in guinea pig left ventricle (beta 1) and lung (beta 2), indicating that kidney receptor subtypes are pharmacologically identical with those in the ventricle and lung, respectively. In the isolated perfused rat kidney, the apparent pA2 values of beta 1-selective blockers for inhibition of isoprenaline-stimulated renin release correlated well with pKD beta 1, but not with pKD beta 2 values. These results clearly show that the beta 1-adrenoceptor subtype mediates renin release in the rat kidney.

Effect of spleen exposure to ultrasound on cellular and antibody-mediated immune reactions in man.

Spleen exposure to ultrasound has been reported to influence antibody response to sheep red blood cell injection in mice (decreased hemagglutination and hemolytic titers and IgM, IgG2a and IgG2b levels and elevated IgG1 levels). In a controlled clinical trial, we investigated the possible immunosuppressive side-effect of splenic exposure (2.0 mW/m2, 3.5 MHz, 5 minutes) to ultrasound on the immune response to Rubella vaccination in 41 anti-Rubella antibody-negative volunteers. The measured parameters (blood cell count, IgA, IgM, IgG including subclasses IgG1-IgG4, isoagglutinins, anti-Rubella hemagglutinin and hemolysin titers, complement C3, skin tests to mumps and tuberculin, T, B and O lymphocytes, esterase-positive and negative T-cell subsets) suggest changes dependent on the time of vaccination, but provide no evidence of an immunosuppressive effect of ultrasound in man.

Gait variability in community-dwelling older adults.

OBJECTIVES: To describe gait variability at usual and fast walking speeds in community-dwelling older adults and to describe the effects of increasing gait speed on gait variability. DESIGN: Cross-sectional, descriptive study. SETTING: The Cardiovascular Health Study at the University of Pittsburgh. PARTICIPANTS: Ninety-five community-living older adults, 54 women and 41 men, age 65 and older (mean age +/- standard deviation 79.4 +/- 3.37). MEASUREMENTS: Gait measured at participant's usual and fast walking speed collected using an instrumented walkway. Step-length and step-width variability were determined using the coefficient of variation. RESULTS: Step-length variability was greatest in those who walked the slowest (r = -0.66, P < .001); step-width variability was smallest in those who walked the slowest (r -0.37, P < .001). Individuals who could not increase their walking speed (<0.10 m/second) on command had an increase in step-length variability and a decrease in step-width variability, whereas those who could increase their speed (>0.10 m/second) had an increase in step-width variability when walking at a faster speed. CONCLUSIONS: Step-length and step-width variability have opposite associations with gait speed in older adults. Improvement in step-length and step-width variability with attempted acceleration might be a key factor to examine in future studies of disability risk and therapeutic interventions.

(+/-)[125Iodo] cyanopindolol, a new ligand for beta-adrenoceptors: identification and quantitation of subclasses of beta-adrenoceptors in guinea pig.

(+/-)[125Iodo] cyanopindolol (ICYP) is a radioligand which binds with an extraordinarily high affinity and specificity to beta-adrenoceptors. In contrast to (+/-) [125Ido]-hydroxybenzylpindolol (IHYP), the new ligand has neither affinity to alpha-nor to 5-HT-receptors. The dissociation constants of ICYP for beta- adrenoceptors in various tissues range from 27 to 40 pM, thereby exceeding the affinity of IHYP by a factor of approximately 3. ICYP does not discriminate between beta 1- and beta 2-adrenoceptors. Therefore, the densities of the two receptor subtypes can be determined from competition curves of ICYP by drugs previously found to show in vitro selectivity for beta 1-adrenoceptors. The guinea pig left ventricle contains only beta 1-adrenoceptors, whereas in a lung tissue, the ratio of beta 1-to beta 2-adrenoceptors is 1 to 4. The calculated affinities of five beta 1-selective antagonists for beta 1-adrenoceptors were nearly identical in the ventricle and the lung. Kinetic studies of ICYP binding to guinea pig lung membranes indicated that the dissociation reaction consists of two components, a fast process (t 1/2 = 9 min) and a slower process (t 1/2 = 8.8 h). A mathematical treatment revealed two possibilities of interpretation: 1. Two forms of the receptor exist which are interconvertible. 2. The (+)- and (-)- enantiomers of ICYP dissociate with different rate constants. The low dissociation constant of ICYP in combination with its high specific radioactivity (2175 Ci mmole -1) allows binding studies to be carried out with small protein and ligand concentrations, e.g. 3 microgram protein per assay in guinea pig lung membranes.

DPI 201-106, a novel cardioactive agent. Combination of cAMP-independent positive inotropic, negative chronotropic, action potential prolonging and coronary dilatory properties.

The in vitro cardiac effects of DPI 201-106, a novel piperazinyl-indole, were investigated. DPI 201-106 produced concentration-dependent positive inotropic effects in guinea-pig and rat left atria, kitten, rabbit and guinea-pig papillary muscles and Langendorff perfused hearts of rabbits between 10(-7) and 3 X 10(-6) mol/l. During isometric twitches, contraction and relaxation phases were prolonged in guinea-pig left atria and right ventricular papillary muscles from kitten and guinea-pigs. Spontaneous sinus rate was decreased in right atria of guinea-pigs and rats. Coronary flow increased in rabbit isolated hearts. Functional refractory period was increased in left atria from guinea-pigs and rats with EC50 values of 1.7 and 0.24 mumol/l respectively. In electrophysiological measurements, DPI 201-106 prolonged the action potential duration (APD70) in guinea-pig papillary muscles up to 70% and in rabbit atria up to 120% at 3 mumol/l. Other action potential characteristics were not changed in guinea-pig papillary muscles but Vmax was decreased in rabbit left atria. The electrophysiological as well as the positive inotropic effects were stereoselective with the activity residing in the S-enantiomer. DPI 201-106 increased the Ca2+-sensitivity of skinned fibres from porcine trabecula septomarginalis with an EC50 of 0.2 nmol/l. DPI 201-106 dit not change cAMP levels in guinea-pig atria and rabbit papillary muscles. Slow action potentials were not induced by DPI 201-106 in partially depolarized guinea-pig papillary muscles. Phosphodiesterase activity of rat hearts was not inhibited by DPI 201-106 at pharmacologically relevant concentrations. The presence of propranolol did not influence the inotropic potency of DPI 201-106 in guinea-pig atria. In conclusion, DPI 201-106 represents a novel type of positive inotropic agents with a synergistic sarcolemmal and intracellular mechanism of action.

Effect of pentoxifylline on sickle cell thalassaemia: haemorheological and clinical results.

The effect of pentoxifylline on the deformability of red cells in sickle cell thalassaemia was investigated. The fluidity of the blood in sickle cell thalassaemia is disturbed and is accompanied by violent pains and irreversible tissue damage caused by capillary occlusions. After treating a 15-years-old female patient with pentoxifylline (2 g orally each day), the fluidity of the blood improved distinctly, and this correlated with a condition free of clinical symptoms. Erythrocyte filtration by Nuclepore filter increased significantly over the 6-month examination period (initial value: V rel = 0.068 +/- 0.008; after 6 months medication: 0.246 +/- 0.030). In addition, in the single-pore erythrocyte rigidometer (SER) a significantly improved passage time of individual erythrocytes could be demonstrated (initial value: 62.43 +/- 15.72 ms; after 4 weeks medication: 28.13 +/- 7.0 ms). The hitherto high number of rheological occlusions in the SER (48 +/- 30.9 from 200 individual passages) almost completely disappeared after treatment (1.7 +/- 1.2).

Cardiovascular actions of DPI 201-106, a novel cardiotonic agent.

DPI 201-106 (4-[3-(4-diphenylmethyl-1-piperazinyl)-2-hydroxypropoxy]-1H-indole -2- carbonitrile) is characterized by a marked cardiotonic activity. The compound exerted positive inotropic effects in anesthetized and conscious dogs, pithed open-chest cats, and isolated hearts of cardiomyopathic hamsters and vanadate-treated guinea-pig atria. Left ventricular dP/dtmax was increased in anesthetized dogs after i.v. injection of 0.2 and 2 mg/kg DPI 201-106 (34 +/- 6 and 104 +/- 18%, respectively) and in unanesthetized dogs after oral doses of 2-8 mg/kg (22 +/- 3 to 50 +/- 5%, respectively). In most experiments, the compound lowered blood pressure and heart rate. Stroke work and left ventricular work were almost unaffected by DPI 201-106, and oxygen consumption and cardiac efficiency remained unchanged in open-chest dogs. Studies of the mechanism of action of DPI 201-106 lead to the conclusion that its positive inotropic effect is not explainable either by beta-stimulation or by liberation of catecholamines. This was shown in anesthetized dogs and pithed open-chest cats pretreated with propranolol and reserpine.

Classic conditioning and dysfunctional cognitions in patients with panic disorder and agoraphobia treated with an implantable cardioverter/defibrillator.

OBJECTIVE: A model for the development of anxiety disorders (panic disorder with or without agoraphobia) is needed. Patients with an implantable cardioverter/defibrillator (ICD) are exposed to repeated electric shocks. If the theory of anxiety development by aversive classic conditioning processes is valid, these repeated shocks should lead to an increased risk of anxiety disorders. To study this hypothesis, we retrospectively studied 72 patients after implantation of an automatic ICD. METHODS: Patients were assessed with the semistructured Diagnostic Interview of Psychiatric Disease 1 to 6 years after implantation of an automatic ICD. Panic disorder and/or agoraphobia was diagnosed in patients who fulfilled all DSM-III-R criteria for those conditions. RESULTS: Anxiety disorder developed in 15.9% of patients after ICD implantation. This was significantly related to the frequency of repeated defibrillation (shocks) to stop malignant ventricular arrhythmias. Dysfunctional cognitions are an additional vulnerability factor. CONCLUSIONS: The data support both the conditioning hypothesis and the cognitive model of anxiety development. These findings suggest that ICD patients are an appropriate risk population for a prospective study of the development of anxiety disorders.

Effects of flecainide on electrophysiological properties of accessory pathways in the Wolff-Parkinson-White syndrome.

The effect of flecainide in 12 patients with the Wolff-Parkinson-White syndrome was analyzed with respect to the anterograde and retrograde conduction properties of the accessory pathway, the modes of initiation and termination of circus movement tachycardias, and the ventricular response during induced atrial fibrillation. The principal effect of this drug was to depress both anterograde and retrograde conduction of the accessory pathway. In 8/9 cases circus movement tachycardia was terminated by prolongation of the retrograde effective refractory period of the accessory pathway. Flecainide increased the shortest and the mean cycle length during induced atrial fibrillation. It is concluded that the drug may be of potential benefit in patients with paroxysmal supraventricular tachycardias in patients with the Wolff-Parkinson-White syndrome.