Cholinergic balance in dementia with Lewy bodies: reversible worsening of Parkinsonism at rivastigmine dosage modulation

We describe a patient with probable dementia with Lewy bodies (DLB) whose Parkinsonism worsened after administration of rivastigmine within the therapeutic dose range. Some extrapyramidal signs (EPS) then reversed to pre-treatment level after rivastigmine dose reduction. We draw attention to the need of EPS monitoring during titration of cholinesterase inhibitors in patients with DLB. This is the first report to our knowledge of iatrogenic worsening of Parkinsonism which was successfully managed by dose reduction.

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Sommario Si descrive il caso di un paziente affetto da Demenza a corpi di Lewy (Dementia with Lewy Bodies, DLB) probabile, in cui si è assistito ad un peggioramento del parkinsonismo dopo somministrazione di rivastigmina a dosi terapeutiche. Alcuni segni extrapiramidali sono regrediti al livello pre-trattamento con una riduzione posologica di rivastigmina. Si sottolinea la necessità di un monitoraggio dei segni extrapiramidali durante la titolazione della terapia con inibitori dell’acetilcolinesterasi cerebrale in pazienti con DLB. Questo è il primo caso descritto, a nostra conoscenza, di un peggioramento iatrogeno di parkinsonismo efficacemente gestito con una riduzione posologica della terapia con rivastigmina.

     

Characterization and Management of Arrhythmic Events in Young Patients With Brugada Syndrome

Background

Information on young patients with Brugada syndrome (BrS) and arrhythmic events (AEs) is limited.

Implantable defibrillator event rates in patients with unexplained syncope and inducible sustained ventricular tachyarrhythmias: a comparison with patients known to have sustained ventricular tachycardia

OBJECTIVES

To assess the clinical significance of inducible ventricular tachyarrhythmias among patients with unexplained syncope.

BACKGROUND

Induction of sustained ventricular arrhythmias at electrophysiology study in patients with unexplained syncope and structural heart disease is usually assigned diagnostic significance. However, the true frequency of subsequent spontaneous ventricular tachyarrhythmias in the absence of antiarrhythmic medications is unknown.

METHODS

In a retrospective case-control study, the incidence of implantable cardiac defibrillator (ICD) therapies for sustained ventricular arrhythmias among patients with unexplained syncope or near syncope (syncope group, n = 22) was compared with that of a control group of patients (n = 32) with clinically documented sustained ventricular tachycardia (VT). Sustained ventricular arrhythmias were inducible in both groups and neither group received antiarrhythmic medications. All ICDs had stored electrograms or RR intervals. Clinical variables were similar between groups except that congestive cardiac failure was more common in the syncope group.

RESULTS

Kaplan-Meier analysis of the time to first appropriate ICD therapy for syncope and control groups produced overlapping curves (p = 0.9), with 57 ± 11% and 50 ± 9%, respectively, receiving ICD therapy by one year. In both groups, the induced arrhythmia was significantly faster than spontaneous arrhythmias, but the cycle lengths of induced and spontaneous arrhythmias were positively correlated (R = 0.6, p < 0.0001). During follow-up, three cardiac transplantations and seven deaths occurred in the syncope group, and two transplantations and five deaths occurred in the control group (36-month survival without transplant 52 ± 11% and 83 ± 7%, respectively, p = 0.03).

CONCLUSIONS

In patients with unexplained syncope, structural heart disease and inducible sustained ventricular arrhythmias, spontaneous sustained ventricular arrhythmias occur commonly and at a similar rate to patients with documented sustained VT. Thus, electrophysiologic testing in unexplained syncope can identify those at risk of potentially life-threatening tachyarrhythmias, and aggressive treatment of these patients is warranted.     

Differential responses to JNJ‐37822681, a specific and fast dissociating dopamine D2 receptor antagonist,in cynomolgus monkey and Sprague–Dawley rat general toxicology studies: clinical observations,prolactin levels,mammary histopathology findings and toxicokinetics

JNJ‐37822681 is a potent, specific and fast dissociating dopamine D₂ receptor antagonist intended for the treatment of schizophrenia. Its nonclinical toxicological profile was investigated in a series of general repeat dose toxicity studies in cynomolgus monkeys and Sprague–Dawley rats. The maximum duration of treatment was 9 and 6 months, respectively. Interspecies differences were noted in the response to JNJ‐37822681 in terms of extrapyramidal (EPS)‐like clinical signs and prolactin‐mediated tissue changes in the mammary gland. Monkeys showed severe EPS‐like clinical signs such as abnormal posture, abnormal eye movements and hallucination‐like behavior at relatively low exposures compared to those associated with EPS in patients with schizophrenia. The high sensitivity of the monkey to JNJ‐37822681‐induced EPS‐like signs was unexpected based on the fast dissociating properties of the compound. Rats, however, were not prone to EPS. Elevated serum prolactin levels were found in rats and monkeys. While rats showed slight to moderate prolactin‐related tissue changes upon histopathological examination in all studies, which among others affected the mammary gland, only minor mammary gland tissue changes were noted in monkeys. Prolactin levels were only slightly increased in patients with schizophrenia receiving relatively high dose levels of JNJ‐37822681. The monkey toxicology studies did not provide an exposure‐based safety margin, while in rats adverse effects were only noted at exposures considerably higher than those achieved at efficacious plasma concentrations in the clinic. Overall, the available data suggest that the cynomolgus monkey showed better predictivity towards the nature of JNJ‐37822681‐associated adverse events in humans than the Sprague–Dawley rat. Copyright © 2013 John Wiley & Sons, Ltd.     

淫羊藿多糖硫酸化修饰条件的优化

目的 优化淫羊藿多糖硫酸化修饰的最佳条件.方法 采用氯磺酸-吡啶法.以硫酸基取代度和糖的质量分数为指标,采用L9(34)正交试验对反应温度、试剂配比和反应时间进行优选.结果 反应温度对修饰的影响最大,适宜的修饰条件为反应温度80℃,氯磺酸与吡啶的体积比在1:8～1:10,反应时间2～3h.结论 采用优化的条件对淫羊藿多糖进行硫酸化修饰可以获得理想的硫酸化淫羊藿多糖.     

Risk factors for encapsulating peritoneal sclerosis in patients who have experienced peritoneal dialysis treatment

Background The present study was conducted to clarify the clinical risk factors related to the development of encapsulating peritoneal sclerosis (EPS), which is one of the most serious complications in patients undergoing peritoneal dialysis (PD).Methods The records of 78 patients with a history of PD treatment, including 18 with EPS, were retrospectively analyzed (male/female, 51:27; age, 51.8 ± 11.0 years; PD treatment, 94.1 ± 42.7 months). The inclusion criteria were: duration of PD more than 24 months; 36-month follow up after discontinuation of PD; available data for dialysate-to-plasma creatinine ratio (D/P Cr), by fast peritoneal equilibration test within 3 months before PD discontinuation; and absence of EPS at PD discontinuation. Analytical parameters included age, sex, underlying renal disease, duration of PD, membrane transport state (higher transporter or lower transporter: D/P cr ratio more than or less than 0.75), number of episodes of peritonitis during PD treatment, performance of peritoneal lavage after PD discontinuation, and reasons for PD withdrawal (ultrafiltration failure, acute peritonitis, social matters).Results Significant differences were noted regarding the PD duration, D/P cr, higher membrane transport state, and number of peritonitis episodes during PD. On receiver operating characteristic curves, the cutoff points for EPS were: D/P cr ratio, 0.74; number of peritonitis episodes, 2; and PD duration (months), 115.2. Multivariate analysis, employing the factors age, PD duration, higher membrane transport state, and number of peritonitis episodes, which were selected by stepwise analysis, identified the latter two factors as significant for the development of EPS (odds ratio [OR], 4.0; P = 0.046 and OR, 12.0; P = 0.049, respectively).Conclusions A higher transporter membrane state and the number of peritonitis episodes are factors contributing to the occurrence of EPS in patients who have experienced PD treatment.     

前列腺液IL-6、IL-8在诊断BPH合并CP的临床意义

目的探讨前列腺液(EPS)内IL-6(白细胞介素6)、IL-8浓度水平对区分单纯良性前列腺增生(BPH)和BPH合并慢性前列腺炎(CP)的意义。方法 100例前列腺手术的BPH病人,在术前行前列腺液IL-6、IL-8浓度检测。术中取前列腺组织标本,根据病理前列腺炎诊断标准确定单纯BPH患者与BPH合并CP患者。结果 BPH合并CP病人EPS中IL-6、L-8浓度较单纯BPH病人明显升高(P<0.01或P<0.05)。结论 EPS中IL-6、IL-8浓度水平与BPH患者是否伴发CP的关系密切,二者在区别单纯BPH与BPH合并CP时具有较高价值。