Point mutation in the parkin gene on patients with Parkinson’s disease

Summary To investigate the distribution of possible novel mutations from parkin gene in variant subset of patients with Parkinson’s disease (PD) in China and explore whether parkin gene plays an important role in the pathogenesis of PD, 70 patients were divided into early-onset group and late-onset group; 70 healthy subjects were included as controls. Genomic DNA from 70 normal controls and from those of PD patients were extracted from peripheral blood leukocytes by using standard procedures. Mutations of parkin gene (exon 1–12) in all the subjects were screened by PCR-single strand conformation polymorphism (SSCP), and further sequencing was performed in the samples with abnormal SSCP results, in order to confirm the mutation and its location. A new missense mutation Gly284Arg in a patient and 3 abnormal bands in SSCP electrophoresis from samples of another 3 patients were found. All the DNA variants were sourced from the samples of the patients with early-onset PD. It was concluded that Parkin point mutation also partially contributes to the development of early-onset Parkinson’s disease in Chinese. WANG Tao, male, born in 1961, Associate Professor This work was supported by grants from the key program of the special scientific project of Scientific & Technologic Agency of Hubei Province (Serial No. 2001AA308B01) and the Hygienic Research Project of Hygienic Agency of Hubei province (Serial No. WJ 01529).     

Olfaction in essential tremor patients with and without isolated rest tremor.

An olfactory deficit is present in patients with essential tremor (ET), but it is often milder than that in patients with Parkinson's disease (PD). In both, the deficit occurs early in the disease. Isolated rest tremor without other signs of parkinsonism can occur in patients with ET. If the rest tremor in these patients represents a manifestation of ET rather than early PD, we hypothesized that their University of Pennsylvania Smell Identification Test (UPSIT) scores would be similar to those of ET patients without rest tremor. The mean UPSIT score in 13 ET patients with isolated rest tremor did not differ from that of 58 ET patients without rest tremor (29.3 +/- 4.3 vs. 29.4 +/- 6.4; P = 0.69). Several ET patients with rest tremor had UPSIT scores that fell outside of the range that is seen in 95% of patients with PD. These data raise the possibility that some ET patients with isolated rest tremor may not have early PD and that the pathological process that is responsible for their ET is also involving the basal ganglia.     

幼儿园824名3－6岁幼儿肝功能、乙肝表面抗原检测结果分析

为了解幼儿的肝功能和ＨＢｓＡｇ携带情况，我们于１９９１年肝炎发病高峰季节对我县四所幼儿园共８２４名幼儿进行了ＡＬＴ、ＴＴＴ、ＺｎＴＴ、ＨＢｓＡｇ检测。结果ＡＬＴ、ＴＴＴ均升高１例，有体征；ＡＬＴ单项升高６例，无症状；ＨＢｓＡｇ阳性５８例，其中９例ＡＬＴ升高，４例ＴＴＴ升高。幼儿园是幼儿集中的地方、同吃、同住、接触密切，对ＨＢｓＡｇ阴性者接种乙肝疫苗，对ＡＬＴ升高者不能忽视以免发生肝炎流行。     

Calculation of Hydrolytic Rate Constants of Poly(ortho ester)s from Molecular Weights Determined by Gel Permeation Chromatography

Purpose. To obtained rate constants from weight-averaged (M_w) or z-averaged (M_z) molecular weights for polymers of Schule-Flory distribution and undergoing random scission. These constants were compared with those obtained by parallel ¹HNMR studies. Methods. The hydrolysis of two poly(ortho ester)s were followed by ¹HNMR and gel permeation chromatography (GPC). Results. Equations to convert number-averaged (M_n), M_w and M_z into fraction of backbone remaining (f_c) were derived. First-order hydrolytic rate constants of two poly(ortho ester)s; DETOSU-HD and DETOSU-CDM were calculated using these relationships. The rate constants calculated from ¹HNMR, M_z and M_w were 0.215, 0.218 and 0.182 hr^–1, respectively, for DETOSU-CDM and 0.152, 0.086 and 0.038 hr^–l for DETOSU-HD. The large discrepancy in the rates determined by ¹HNMR and GPC in the latter case was attributed to that the detector response (refractive index) of the monomers was lower than that of the high molecular weight polymer. The difference is small in the case of DETOSU-CDM, and the rates calculated from GPC data were comparable or nearly identical to that obtained from ¹HNMR data. Conclusions. Although GPC can yield rapid and valuable kinetic data for the degradation of biodegradable polymers, the system, however, must be carefully calibrated to account for the variations in Mark-Houwink coefficients and in the response of the mass detector between the high and low MW polymers.     

Prospective study of phobic anxiety and risk of Parkinson's disease.

Anxiety disorders are common in Parkinson's disease (PD). However, the risk of PD among people with anxiety has not been examined in a prospective cohort study. We examined this relation prospectively within the Health Professionals Follow-Up Study, a cohort of US male health professionals. In 1988, anxiety was assessed using the Crown-Crisp phobic anxiety index in 35,815 men without PD, stroke, or cancer at baseline. There were 189 incident cases of PD during 12 years of follow-up. After adjusting for age, smoking, and caffeine intake, the relative risk of PD among men with the highest level of anxiety (Crown-Crisp index scores of 4 and above) was 1.5 (95% CI = 1.0-2.1; P-trend = 0.01) compared to men with the lowest level of anxiety. This positive association persisted after excluding cases of PD with onset in the first 2 years of follow-up. Use of anxiolytic medication was also associated with an elevated risk of PD (RR= 1.6; 95% CI = 0.9-3.1), but adjusting for this potential confounder did not materially affect the association between anxiety and risk of PD. Our results suggest that anxiety is a risk factor for PD. Whether this association is causal or the result of shared underlying biology remains a question.     

Visual function in Huntington's disease patients and presymptomatic gene carriers.

Disturbances of visual cognition, visuomotor performance, and visual memory have been described frequently in Huntington's disease (HD). Early stage visual abnormalities could contribute to these deficits. We evaluated visual processing in 20 control subjects who were non-gene carriers at risk for HD, nine presymptomatic gene-positive subjects, and eight subjects with a recent diagnosis of Huntington's disease. Visual perceptual tests of contrast sensitivity and motion discrimination were used to probe early stage visual processing. Extraocular movements were evaluated in a neurologic examination, and the Digit Symbol test was used to test visual motor performance. Contrast sensitivity did not differ among the three groups. Motion discrimination was impaired in HD subjects but not in the presymptomatic gene carriers when compared to gene noncarriers. Among gene carriers, impaired motion discrimination performance was associated with poorer Digit Symbol performance and extraocular abnormalities. These findings suggest that the early stages of HD are associated with disturbances of motion perception as well as disruptions of visual motor and ocular motor performance.     

Parkinsonism associated with Addison's disease.

We describe a 35-year-old woman who developed parkinsonism in association with Addison's disease. The parkinsonism disappeared following treatment for Addison's disease without the use of antiparkinsonian drugs. This association stands unique although the pathophysiology remains unclear.     

Flumazenil, a GABA antagonist, may improve features of Parkinson's disease.

Manipulation of gamma-aminobutyrate (GABA) system has been little studied in Parkinson's disease, despite the fact that GABA subserves a large part of the basal ganglia, including the outflow tracts. To test whether antagonism of GABA could improve features of PD, we administered open label intravenous flumazenil to eight practically defined off patients and assessed UPDRS scores, bilateral 1-minute hand-tapping speed, and timed gait tests. Patients demonstrated significantly greater tapping speed, which peaked 40 minutes after injection (P < 0.05). Total motor Unified Parkinson's Disease Rating Scale scores modestly improved (P < 0.05). There were no adverse events. Mechanisms by which flumazenil could improve PD are discussed.     

青年人大肠癌误诊原因探讨

目的 探讨青年人大肠癌的误诊原因，以便早期诊断治疗。方法 回顾性分析62例青年人大肠癌的诊断及其治疗效果。结果 本组直肠癌36例中被误诊为结肠炎7例，痔疮并出血5例，痢疾3例，肛周脓肿并肛瘘2例；结肠癌26例中被误诊为阑尾周围脓肿3例，结肠炎2例，缺铁性贫血1例。误诊率37．1％。结论 青年人大肠癌早期临床症状不明显，恶性程度高，预后差,其治疗水平有赖于对这些特征的认识，力争早期诊断及治疗。     

Health status measurement in Parkinson's disease: validity of the PDQ-39 and Nottingham Health Profile.

We assessed the feasibility and psychometric properties of two commonly used health status questionnaires in Parkinson's disease (PD): the generic Nottingham Health Profile (NHP) and the disease-specific 39-item Parkinson's disease Questionnaire (PDQ-39), from a cross-sectional postal survey of PD patients (N = 81), using traditional and Rasch measurement methodologies. Overall response rate was 88%. Both questionnaires were found feasible, although the NHP performed less well. The PDQ-39 had fewer floor effects and was better able to separate respondents into distinct groups than the NHP, whereas the latter exhibited less ambiguous dimensionality and better targeting of respondents with non-extreme scores. Reliability and validity indices were similar, and potential differential item functioning by age and gender groups was found for both questionnaires. PDQ-39 response alternatives indicated ambiguity. With few exceptions, questionnaire scales were unable to meet recommended standards fully. While preliminary, this study illustrates the need for thorough evaluation of outcome measures and has implications beyond the questionnaires used here. Although promising, both questionnaires warrant further developmental work and stronger support of measurement validity before they could be considered fully suitable for valid use in PD, in particular in earlier stages of the disease.