Early-onset Parkinson's disease in a Chinese population: 99mTc-TRODAT-1 SPECT, Parkin gene analysis and clinical study

Early Onset Parkinson's Disease (EOPD) is characterized by selective degeneration of nigrostriatal dopaminergic neurons and a marked response to levodopa. However, at present, few methods are available as diagnostic tools for EOPD except for 18F-DOPA PET. In addition, little is known about the correlation between clinical severity, neuroimaging grading and genetic susceptibility. In the present study, 99mTc-TRODAT-1 SPECT and brain MRI were used to identify 30 cases of non-familial EOPD from a Chinese cohort of 230. All 30 PD patients had an age of onset of less than 55 years (mean age at onset, 41.5+/-9.3 years). Each of the 30 EOPD cases was sub-classified into one of five stages based on the 99mTc-TRODAT-1 SPECT findings. In the early stages of PD (stages 1 and 2), a lower uptake of 99mTc-TRODAT-1 in the putamen was found, while uptake in the caudate nucleus was normal. In the latter stages (stages 3, 4, 5), 24 patients revealed a diffuse and uniform loss of 99mTc-TRODAT-1 uptake in the putamen and the caudate nucleus. Further, in conventional genetic studies of the 30 patients, six novel mutations were found in the Parkin gene, and these included five heterozygous point mutations (C441R, Q311H, V258M, C212G, and S193I) and one homozygous deletion (exon 10-12). Known polymorphisms (Ser167Asn, Val380Leu) were also found in a number of patients. However, gene dosage analysis did not reveal any compound heterozygous mutations in these 30 patients using quantitative duplex PCR. This is the first study to examine EOPD patients of Chinese ethnic background (not exhibiting a definite familial trait), to offer a complete genetic analysis of the Parkin gene, and to correlate clinical stages of the disease with dopamine re-uptake.     

Hyperintense putaminal rim sign is not a hallmark of multiple system atrophy at 3T

BACKGROUND AND PURPOSE: Hyperintense putaminal rim (HPR) on the T2-weighted imaging, which has been observed in our daily practice while reading 3T brain images, has been described as a finding typical of multiple system atrophy (MSA). We hypothesized that the HPR sign is not an exclusive hallmark of MSA at a high magnetic field strength, but rather may be a normal finding. METHODS: Ten consecutive clinically healthy age-matched adults who showed recognizable HPR at 3T were subsequently examined on a 1.5T imaging system within 2 hours. MR examination included axial T2-weighted fast spin-echo (FSE), fluid attenuated inversion recovery (FLAIR) on a 3T scanner, and equivalent T2-weighted FSE at 1.5T. MR images were obtained parallel to the intercommissural plane. All the images were interpreted by 2 experienced neuroradiologists. RESULTS: All 10 subjects (3 men and 7 women; aged 52 +/- 6.1 years [range, 44-61 years], expressed as mean +/- SD) with the positive HPR sign on axial T2-weighted FSE at 3T had negative findings at 1.5T. Such hyperintense rim was also vague or absent on the 3T-FLAIR images. CONCLUSION: Our data suggest that the HPR at 3T scans is a nonspecific, normal finding. FLAIR may be helpful in discriminating between normal subjects and patients with MSA in case of isolated HPR at 3T.     

Environmental barriers and mobility in Taiwan: is the Roy adaptation model applicable?

This study tested Roy's adaptation model by exploring the relationship between environmental stimuli, specifically barriers, and the mobility, and instrumental behaviors of hip-fractured elderly persons after surgery in Taiwan. A prospective study was conducted 3 months after hospital discharge with 87 elderly persons with hip fracture who had received surgery at a medical center in northern Taiwan. After controlling for prefracture conditions, subjective environmental barriers significantly diminished the walking ability, self-care ability, and role performance of hipfractured elderly persons. The findings of this study lend to suggestions for intervening with hip-fractured elderly persons after surgery.     

Cysts of the tunica albuginea

The authors report 3 cases of cysts of the tunica albuginea. Scrotal ultrasonography facilitates preoperative diagnosis and helps to avoid orchiectomy or to prevent unnecessary surgery.     

Establishment and characterization of a human gastric carcinoma cell line TMC-1

Established cancer cell lines are useful in the study of various cancers. We established a human gastric carcinoma cell line TMC-1 derived from the lymph node of a moderately differentiated adenocarcinoma of the stomach. TMC-1 cells grew in vitro as a mixture of attached and suspension cells, and exhibited spindle or ovoid morphology. They had a population doubling time of 15 h, a plating efficiency of 61%, formed colonies in semisolid agar, secreted the tumor marker CA 19-9, and were tumorigenic in athymic nude mice. The cells expressed E-cadherin and beta-catenin. The karyotypic analysis demonstrated hyperdiploid features with a modal chromosome of 53. The cell had the deletion at chromosome 18q and gains at chromosome 2p13-25, 5p15, 5q21-35, 7, 8q24, 9q, 11, 12p, 14q24-32 and 20. Analysis by fluorescence in situ hybridization showed the deletion at 7qtel and duplication at 7q11.2 at the rearranged chromosome 7. Growth of TMC-1 cells was inhibited by 27-32% by interferon-alpha (2,000 U/ml) and by interferon-gamma with an IC50 of 125 U/ml. The cell line is tumorigenic in vivo, and its growth is moderately inhibited by interferon-alpha and interferon-gamma. It can be used to develop new modalities of human gastric cancer treatment.     

A method for direct thalamic stimulation in fMRI studies using a glass-coated carbon fiber electrode

Recent fMRI studies are of interest in exploring long-range interactions between different brain structures and the functional activation of specific brain regions by known neuroanatomical pathways. One of the experimental approaches requires the invasive implantation of an intracranial electrode to excite specific brain structures. In the present report, we describe a procedure for the production of a glass-coated carbon fiber electrode and the use of this electrode for direct activation of the brain in fMRI studies. The glass-coated carbon fiber microelectrode was implanted in the medial thalamus of anaesthetized rats and T2*-weighted gradient echo images in the sagittal plane obtained on a 4.7 T system (Biospec BMT 47/40) during electrical stimulation of the medial thalamus. The image quality obtained using this electrode was acceptable without reduction of the signal-to-noise ratio and image distortion. Cross-correlation analysis showed that the signal intensities of activated areas in the ipsilateral anterior cingulate cortex were significantly increased by about 4-5% during medial thalamus stimulation. The present study shows that glass-coated carbon fiber electrodes are suitable for fMRI studies and can be used to investigate functional thalamocingulate activation.     

Intrauterine diagnosis of heterotaxy syndrome

Background Heterotaxy syndrome, including right isomerism and left isomerism, is characterized by an abnormal symmetry of the viscera and veins and is frequently associated with complex cardiac anomalies. We sought to define the feasibility of in utero diagnosis and the postnatal outcome. Methods Patients with heterotaxy syndrome were identified from 579 fetal echocardiograms performed from January 1994 to December 1998. The diagnosis was made on the basis of the fetal echocardiographic findings and was confirmed with autopsy or postnatal evaluation. Results A total of 25 fetuses with right isomerism and 4 with left isomerism constitute the study population. The pregnancies of 7 fetuses (6 right and 1 left isomerism) were terminated before the 24th gestational week and subjected to autopsy. Twelve fetuses (10 right and 2 left isomerism) were lost to follow-up. Nine with right isomerism and 1 with left isomerism were delivered and underwent palliation. Among them, 5 patients (56%) with right isomerism died and more than half of the deaths occurred during infancy. The major cardiac anomalies detected and confirmed with postnatal evaluation or autopsy in fetuses with right isomerism were total anomalous pulmonary venous connection (6/15; 40%), common atrium (15/15; 100%), complete atrioventricular canal (15/15; 100%), double outlet right ventricle (15/15; 100%), and pulmonary stenosis (11/15; 73%). The major cardiac anomalies in fetuses with left isomerism were interruption of inferior vena cava (2/2; 100%), common atrium (1/2; 50%), and complete atrioventricular canal (1/2; 50%). Undetected lesions with fetal echocardiogram were abnormal pulmonary venous return to systemic veins in 1 case (sensitivity, 83%; 5/6; and specificity, 90%; 9/10) and outflow obstruction in 1 case (sensitivity, 91%; 11/12; and specificity, 67%; 2/3). Different patterns of rhythm disturbances were identified: supraventricular tachycardia in 1 case with right isomerism and sinus bradycardia with junctional rhythm in 3 cases with left isomerism (2 of them lost to follow-up). After birth, another 2 patients with right isomerism had supraventricular tachycardia, and 1 with left isomerism had sinus bradycardia develop at age 2 years. Conclusion Heterotaxy syndrome is usually detected in fetuses with the sonographic cardiac abnormalities. Visualization of the pulmonary venous return and outflow obstruction and characterization of the rhythm disturbances are feasible. However, in spite of prenatal diagnosis, the prognosis remains poor. (Am Heart J 2002;143:1002-8.)     

Randomized prospective study comparing routine versus selective use of sonography of the complete calf in patients with suspected deep venous thrombosis

OBJECTIVE: We compared patient outcomes using two protocols: one routinely and the other selectively evaluating the calves completely during sonographic assessment of the lower extremities in patients with suspected deep venous thrombosis. SUBJECTS AND METHODS: In this randomized prospective study, patients were assigned to two groups. In one group, the deep calf veins were routinely evaluated in their entirety, and in the other group the calf was not evaluated unless the patient had symptoms or physical signs in the calf, in which case only the areas of symptoms or physical signs were evaluated. Patients were followed up for 3 months by medical record review, physician surveys, and telephone calls. An adverse outcome was a propagated deep venous thrombosis into the thigh or a pulmonary embolus. Examination times were recorded when possible. RESULTS: Of the 235 patients in the group in which the deep calf veins were routinely evaluated, we saw no adverse outcomes (0.0%; 97.5% one-sided confidence interval [CI], 0.6-1.6%). Of the 261 patients in the group in which the calf was only evaluated if there were signs or symptoms, we saw two adverse outcomes (0.8%; 95% CI, 0.1-2.7%). CONCLUSION: We found no significant difference in adverse outcomes in patients undergoing a protocol in which the deep calf veins were routinely evaluated or a protocol in which the calf was evaluated only if physical signs or symptoms were present.     

RARRES3 expression positively correlated to tumour differentiation in tissues of colorectal adenocarcinoma

RARRES3 is a retinoid-inducible class II tumour-suppressor gene. This study analysed the expression of RARRES3 protein in normal, adenoma and carcinoma tissues of the colorectum and its correlation with tumour differentiation. The expression of RARRES3 protein in 151 paraffin-embedded colorectal tissues (11 distal normal mucosa, 20 adenoma and 120 colorectal adenocarcinoma) was determined by immunohistochemistry. RARRES3 protein was expressed in all 11 distal normal, 120 adjacent normal and 20 adenoma tissues. In distal normal tissues, RARRES3 protein was expressed at the highest levels in differentiated mucosal epithelial cells. Among 120 carcinoma tissues, RARRES3 protein was detected in 97.6% (40 out of 41), 79.4% (54 out of 68) and 17.3% (three out of 11) of well-, moderately and poorly differentiated tumours, respectively. The expression of RARRES3 protein was positively correlated to tumour differentiation (test for trend, P<0.0001). Also, levels of RARRES3 protein were found to be higher in the normal tissues adjacent to 14.6% (six out of 41), 51.5% (35 out of 68), and 90.1% (10 out of 11) of well-, moderately and poorly differentiated tumours, respectively. The decreases in tumour differentiation and RARRES3 expression were significantly correlated compared to the adjacent normal tissues (test for trend, P<0.0001). The prognostic implication of RARRES3 protein expression was studied in 107 tumour, and no statistical difference in survival was observed. The expression of RARRES3 protein was positively correlated to cellular differentiation of normal and adenocarcinoma tissues of the colorectum, which supports the role of RARRES3 in normal and malignant epithelial differentiation of colorectum. RARRES3 expression was decreased only in carcinoma tissue, which suggests that altered RARRES3 expression occurs late in colorectal carcinogenesis.