Clinical characteristics of Tourette syndrome

Abstract The aim of the present study was to examine the clinical characteristics of Tourette syndrome (TS) in terms of symptomatology, outcome and organic and genetic factors, and to compare these with results of previous studies on TS in Western countries and in Japan, on the basis of precise information taken from a large number of TS patients under psychiatric treatment in Japan. There was a total of 64 TS patients (55 males and nine females) selected from those who visited our outpatient clinic from 1974 to 1993 and were found to meet the criteria for Tourette's disorder of DSM-III-R. The mean patient age at entry to the present study was 17.4 years (SD:7.2). All data were collected through a systematic chart review of subjects, including data on tic symptoms and the course of their development; complications and developmental histories; family histories; medical and psychological examinations; treatment; severity and outcome. A check of the data showed that the mean age at onset was 6.9 years (SD:2.7). An analysis of the progression of the symptoms revealed that 'generalized tics' afflicting the entire body were found in 64.1% of subjects and coprolalia was found in 50%. The main complications were obsessive-compulsive symptoms (OCS) in 62.5% of patients and attention deficit hyperactivity disorder (ADHD) in 17.2%. Of their parents, 7.0% had tic disorders except TS and 1.6% had TS. Contrary to results from previous studies of TS, our study revealed that at least the incidence of coprolalia in TS patients in Japan is not lower than in Western countries. However, the frequency of familial cases seemed to be lower than previously reported for Western patients. Outcome was fairly related with 'generalized tics,' OCS, aggressiveness and ADHD.     

Outcomes of Ablation of Paroxysmal Atrial Fibrillation in Patients on Chronic Hemodialysis

AF Ablation in HD Patients . Introduction: It is not common for patients on chronic hemodialysis (HD) to undergo catheter ablation of atrial fibrillation (AF). We aimed to show the outcomes of AF ablation in the HD patients. Methods and Results: Thirty HD patients who underwent pulmonary vein (PV) isolation for drug refractory paroxysmal AF were retrospectively studied, and their AF recurrence free rate and frequency of periprocedural complications were compared to 60 age‐ and gender‐matched control patients not requiring HD. A nonirrigated ablation catheter was used in both patient groups. During a mean follow‐up period of 821 ± 218 days, 16 (54%) of the HD patients remained free from AF recurrence without any antiarrhythmic agents versus 47 (78%) of the control patients with an initial ablation (P = 0.013). A second ablation procedure was performed in 12 patients with an AF recurrence, and consequently 20 (67%) of the HD patients were in sinus rhythm compared to 53 (88%) of the controls during a follow‐up duration of 747 ± 221 after the last ablation (P = 0.012). Bleeding from the venipuncture site requiring a prolonged hospital stay was identified in 2 HD patients and 1 control subject, while no life‐threatening complications were observed in either patient group. Conclusion: Although the success rate of the PV isolation in HD patients was far from satisfactory, it may be considered as one of the therapeutic options for them. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1289‐1294, December 2012)     

Differences in the clinical characteristics of Pneumocystis jirovecii pneumonia in immunocompromized patients with and without HIV infection

Background and objective: The incidence of Pneumocystis jirovecii pneumonia (PCP) in patients with predisposing immunodeficiencies other than AIDS is growing. Knowing the different characteristics and outcomes of PCP according to HIV status would help physicians manage and treat patients with PCP. Methods: The medical charts of all patients with a proven first episode of PCP, diagnosed between 1997 and 2007 were retrospectively reviewed, and clinical and laboratory data abstracted. Results: Of the 35 patients with PCP, 18 were HIV‐positive and 17 were HIV‐negative with other immunosuppressive conditions. HIV‐negative patients were significantly older than HIV‐positive patients. The WCC (10 952 ± 5669 vs 9750 ± 3133/µL; P = 0.015), neutrophil counts (9631 ± 5421 vs 5680 ± 2628/µL; P = 0.01) and CD4+ lymphocyte counts (329 ± 502 vs 47 ± 50/µL; P < 0.001) were significantly higher in HIV‐negative patients. Six of the 17 HIV‐negative patients had a CD4+ lymphocyte count >300/µL. Serum IgG levels were lower in HIV‐negative patients (943 ± 379 vs 1635 ± 657 mg/dL; P = 0.017). Mortality was higher in HIV‐negative (52.9%) than in HIV‐positive patients (0%). On univariate analysis, risk factors for mortality from PCP were the presence of underlying pulmonary disease (odds ratio 4.000, 95% CI: 1.501–10.658) and HIV‐negative status (odds ratio 2.125, 95% CI: 1.283–3.518). Conclusions: The characteristics and outcomes of PCP differ significantly depending on HIV status. The existence of underlying pulmonary diseases may be associated with the prognosis of HIV‐negative patients with PCP.     

Clinical characteristics of Japanese patients with familial obstructive sleep apnoea syndrome

Background and objective: Craniofacial structure and body fat are key factors that predispose to upper airway obstruction while asleep, and these phenotypes can be genetically inherited. Neither the clinical characteristics of familial obstructive sleep apnoea syndrome (OSAS) nor the definitive morphological factors responsible for familial occurrence have been well identified. This study compared the clinical and cephalographic characteristics of Japanese patients with familial OSAS, non‐familial OSAS and healthy controls, to clarify the mechanisms underlying familial OSAS. Methods: The study recruited 28 patients with familial OSAS, comprising 14 index cases and 14 first‐degree relatives affected with OSAS, and compared these with age‐ and sex‐matched patients with non‐familial OSAS (n = 32) and healthy subjects (n = 33). Data on clinical status were collected, including the presence of hypertension, BMI and daytime sleepiness measured on the Epworth sleepiness scale. Respiratory function was evaluated by the AHI, % periods in which SpO₂ fell 90% or below and lowest value of SpO₂ on polysomnograms. Information on the first witnessed age of habitual snoring during sleep was collected via interview with patients and/or their family members. A detailed cephalometric assessment was made of each study subject. Results: Patients with familial OSAS had lower mean BMI than did patients with non‐familial OSAS. The first witnessed age of habitual snoring was younger in the familial cases than the non‐familial cases. Cephalometric variables showed that the posterior airway space and the distance between the gonion and the gnathion were significantly smaller in the familial group than in the other two groups. Conclusions: Familial OSAS occurred at a younger age than non‐familial OSAS due to minor anomalies of craniofacial morphology.     

PHARMACOKINETIC STEREOSELECTIVITY OF TROGLITAZONE,AN ANTIDIABETIC AGENT,IN THE KK MOUSE

Troglitazone, an oral antidiabetic agent, is an equal mixture of four stereoisomers involving two asymmetric centres. In the present study, the stereoselectivity of in vitro epimerization in plasma and organ homogenate and in vivo plasma disposition in the KK mouse, an animal model of non-insulin-dependent diabetes, was examined. In the incubation experiments at 37 °C, there was a fivefold to eightfold acceleration of epimerization at the 5 position of the thiazolidine ring in KK mouse plasma compared with that in buffer. However, no inversion at the 2 position of the chroman ring was observed. In addition, there was an approximately 1·3-fold difference in the epimerization rates among stereoisomers at the 2 position of the chroman ring. However, there were no differences in the values of the equilibrium constants of epimerization, and the ratio of epimerization among stereoisomers at the 5 position of thiazolidine ring was almost unity. The acceleration of epimerization is thought to be due to the high degree of protein binding because of the relationship between the initial epimerization rate and the dilution ratio of the plasma. Although acceleration of epimerization was also observed in the 20% homogenates of liver, kidney, and intestine of the KK mouse, the degree of stereoselectivity was lower than in plasma. The analysis of the plasma disposition after intravenous administration of troglitazone stereoisomers, using a kinetic model, indicated that the metabolic clearance in the liver showed a 2·5-fold maximum difference among stereoisomers and that the stereoselectivity of epimerization was low. ©1997 by John Wiley & Sons, Ltd.     

Determination of Protein Binding of Troglitazone Stereoisomers by Fluorometric Titration

Determination of the protein binding of troglitazone is difficult because of its high adsorption to filters and membranes and the instability of the stereoisomers. We attempted to assess the protein binding of four stereoisomers of troglitazone in the plasma and albumin from several species by the method using fluorescent probes. The inhibition constants (K_i) for the stereoisomers of troglitazone were obtained from the decreases in fluorescence intensity of dansylsarcosine caused by competitive inhibition. Each stereoisomer of troglitazone displaced dansylsarcosine, a typical specific fluorescent probe for the diazepam binding site on human serum albumin (HSA). The highest binding affinity for dansylsarcosine was observed with HSA (dissociation constant, K_d,1 = 0·5 μM), while it was lowest in the mouse (K_d,1 = 18 μM). The K_i values for KK and ddY mouse plasma and mouse and rat albumin were in the range 2–15 μM, and there were no large variations among stereoisomers, the maximum differences being twofold. For human plasma and albumin, the displacement could not be accounted for by a simple competitive inhibition. Comparison between unbound fraction ( f_u) values calculated from thus obtained K_i values and those of a mixture of the four stereoisomers determined by high-performance frontal analysis showed that the f_u values obtained by fluorometric titration were higher, while the relative differences among the stereoisomers in terms of animal species and strain were comparable for the two methods. Small differences in protein binding among stereoisomers of troglitazone may not be the major reason for their stereoselective pharmacokinetics. © 1997 John Wiley & Sons, Ltd.     

Japan-Russia Pediatric Society

In March 1990, medical interchange between Japan and the Soviet Union began with a letter from the local health bureau of Khabarovsk. We visited Khabarovsk three times and Kamchatka once, and saw many hospitals and patients. Russian doctors of pediatrics visited Japan. Medical information was exchanged and discussed. The Japan-Russia Pediatric Society was established to perform interchange of medical information, technology and staff such as doctors, nurses and technicians between Japan and Russia, especially the Far East district of Russia. The Society meeting has been held three times: Tokyo (1991), Khabarovsk (1992) and Niigata (1993). It is necessary to continue the interchange between the two countries.