Rapidly progressive parkinsonism in a self-reported user of ecstasy and other drugs.

A 38-year-old man developed parkinsonism that progressed to Hoehn and Yahr stage 5 within 4 years of onset. Response to ropinirole deteriorated, levodopa was not tolerated, and subthalamic nucleus stimulation has provided only partial relief of symptoms. He reported heavy use of Ecstasy through most of his twenties and thirties. His neurological problems may be unrelated to his drug use, but it is also possible they represent an idiosyncratic reaction.     

Suggestive linkage to chromosome 19 in a large Cuban family with late‐onset Parkinson's disease

The identification of disease genes using family‐based approaches has provided important insights into the pathogenesis of Parkinson's disease (PD) demonstrating the importance of genetic studies on monogenic forms of the disease. We studied a large Cuban family with typical, late‐onset PD and probable autosomal dominant inheritance. Mean age at onset was 61.2 years (±12.53, 45–76). Other phenotypes such as essential tremor and atypical parkinsonism were observed in this family. We carried out a genome‐wide scan and linkage analyses. The genetic data were analyzed using a conservative model in which only patients with clinically definite or likely PD were considered affected, other phenotypes were regarded as “unknown.” Multipoint analyses yielded a maximum LOD of 2.26 between markers D19S221 and D19S840. Haplotype analysis showed a region on chromosome 19 shared by six of seven PD patients. The essential tremor phenotype and the atypical parkinsonism do not segregate with this haplotype, suggesting a different etiology. Our findings suggest the presence of a novel locus for PD on chromosome 19p13.3–q12. We propose that an oligogenic model with moderate contribution of two or three genes rather than a “pure” monogenic model might explain better the wide range in age at onset, the reduced penetrance and the phenotypical variability observed in PD families. © 2003 Movement Disorder Society     

Delayed sleep phase syndrome: A placebo-controlled cross-over study on the effects of melatonin administered five hours before the individual dim light melatonin onset

In a double-blind placebo-controlled cross-over study, 30 patients with Delayed Sleep Phase Syndrome (DSPS) were included, of whom 25 finished the study. Melatonin 5 mg was administered during two weeks in a double-blind setting and two weeks in an open setting successively or interrupted by two weeks of placebo. The study's impact was assessed by measurements of the 24-h curves of endogenous melatonin production and rectal temperature (n=14), polysomnography (n=22), actigraphy (n=13), sleep log (n=22), and subjective sleep quality (n=25). Mean dim light melatonin onset (DLMO) (±SD), before treatment, occurred at 23.17 hours (±138 min). Melatonin was administered five hours before the individual DLMO. After treatment, the onset of the nocturnal melatonin profile was significantly advanced by approximately 1.5 hour. Body temperature trough did not advance significantly. During melatonin use, actigraphy showed a significant advance of sleep onset and polysomnography, a significant decreased sleep latency. Sleep architecture was not influenced. During melatonin treatment patients felt significantly more refreshed in the morning. These results show that analysis of DLMO of patients suffering from DSPS is important both for diagnosis and therapy. These results are discussed in terms of the biochemistry of the pineal.     

Is monoamine oxidase inhibitor induced myoclonus serotoninergically mediated?

Summary In the present study a single case observation of myoclonus during sleep-wave transition was monitored in a depressed patient treated with the monoamine oxidase inhibitor, phenelzine. The myoclonus had a rhythm of 1 c/second and lasted for two years, the duration of phenelzine treatment. Myoclonus appeared neither during wakefulness nor during sleep, but at wake-sleep-wake transitions. This switch myoclonus was associated with phasic muscle hyperactivity during REM sleep.Methysergide a 5-HT suppressor, decreased the switch myoclonus frequency and the REM muscle hyperactivity, indicating serotoninergic involvement in the mechanism of phenelzine induced myoclonus.     

成人斯蒂尔病1例

成人斯蒂尔病起病原因及发生机制仍不清楚,临床主要表现为发热、关节痛、皮疹,且有白细胞、血清铁蛋白等指标增高,但缺乏针对该病的特定诊断指标,导致临床漏诊、误诊比率较高。通过查阅相关文献,发现本病内镜下报道资料较少。本文就1例成人斯蒂尔病病例及胃镜下表现进行报道,并结合AOSD相关诊断指标、治疗方面的最新进展进行归纳,旨在为临床诊疗本病寻求更精准的选择。     

Identification of cathepsin C mutations in ethnically diverse papillon-Lefèvre syndrome patients

INTRODUCTION—Papillon-Lefèvre syndrome (PLS) is an autosomal recessive disorder characterised by palmoplantar keratoderma and severe, early onset periodontitis, which results from deficiency of cathepsin C activity secondary to mutations in the cathepsin C gene. To date, 13 different cathepsin C mutations have been reported in PLS patients, all of which are homozygous for a given mutation, reflecting consanguinity.
AIM—To evaluate the generality of cathepsin C mutations in PLS, we studied an ethnically diverse group of 20 unrelated families.
METHODS—Mutations were identified by direct automated sequencing of genomic DNA amplified for exonic regions and associated splice site junctions of the cathepsin C gene. Long range PCR was performed to determine the genomic structure of the cathepsin C gene.
RESULTS—The cathepsin C gene spans over 46 kb, with six introns ranging in size from 1.6 to 22.4 kb. Eleven novel mutations and four previously reported mutations were identified in affected subjects from 14 families. Missense mutations were most common (9/15), followed by nonsense mutations (3/15), insertions (2/15), and deletions (1/15). Among these 14 probands, two were compound heterozygotes. Affected subjects with transgressions of the dermal lesions onto the knees or elbows or both had mutations in both the pro- and mature regions of the enzyme, although most were in the mature region.
CONCLUSION—Mutations in the mature region of cathepsin C were more likely to be associated with the transgressions of the dermatological lesions, although the results were not statistically significant. A comprehensive list of all cathepsin C mutations described to date, representing 25 mutations from 32 families with PLS and related conditions, is also presented.


Keywords: cathepsin C; genetics; severe early onset periodontitis; hyperkeratosis     

Early-onset gastric carcinomas display molecular characteristics distinct from gastric carcinomas occurring at a later age

Gastric cancer is thought to result from a combination of environmental factors and accumulation of specific genetic alterations, and consequently mainly affects older patients (>50 years of age). Fewer than 10% of patients present with the disease before 45 years of age and these young patients are thought to develop carcinomas with a different molecular genetic profile from that of sporadic carcinomas occurring at a later age. Forty early-onset gastric carcinoma resection specimens were characterized for microsatellite instability (MSI) and loss of heterozygosity status using 22 polymorphic microsatellite markers. Twenty-four biopsies were additionally evaluated for the presence of MSI. No MSI was observed in any of the cases analysed. Losses were infrequent, but were most common for the D1S234 (26.1%) and D1S1676 (17.4%) markers, flanking the RUNX3 gene; for the p53ALU (23.1%) and TP53 (15.4%) markers, near the TP53 gene; and for the D16S2624 (17.2%) marker, near the E-cadherin (CDH1) gene. All cases with loss of CDH1, as well as 6/7 cases with loss of TP53, displayed aberrant staining of the corresponding proteins, pointing to a functional role for these proteins in early-onset gastric carcinogenesis. No germline CDH1, TP53 or RUNX3 mutations were detected in any of the cases analysed. No correlation was observed between non-functional E-cadherin and the histological type of the tumours analysed. Finally, Epstein-Barr virus was not detected in any of the cases analysed. On the basis of these results, early-onset gastric carcinomas appear to have characteristics distinct from gastric carcinomas occurring at a later age.