No association between a presenilin 1 polymorphism and Alzheimer disease

BACKGROUND: Homozygosity of allele 1 of a presenilin 1 intron 8 polymorphism (PS1-1) has been associated with doubling of the risk of sporadic late-onset Alzheimer disease (LOAD), in some, but not all studies. OBJECTIVE: To genotype the PS1 intron 8 polymorphism in predominantly Hispanic families with LOAD to test for association and for linkage between this polymorphism and LOAD. DESIGN: A family-based, case-control, genetic-linkage study. SETTING: Predominantly Hispanic families were selected from probands who were part of a random sample of 2128 Medicare beneficiaries aged 65 years or older who were residing in the community of Washington Heights, which is located in the northern part of Manhattan, NY. PARTICIPANTS: Fifty-one families with 103 affected family members, 67 unaffected family members, and 7 family members with other diagnoses were genotyped for the PS1 polymorphism. All patients met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for either probable or possible Alzheimer disease. Age was truncated at 55 years or older. MAIN OUTCOME MEASURES: Association analyses, conditional logistic regression, and traditional linkage methods were applied to the families for the PS1 polymorphism and for the presence of the gene for apolipoprotein E (APOE). Results of the association and conditional logistic regression analyses of PS1 intron 8 polymorphism were subsequently adjusted for the effect of APOE-epsilon4, sex, age, and education of each sibling. RESULTS: No association between the PS1 intron 8 polymorphism and LOAD was observed (relative risk, 0.99; 95% confidence interval, 0.3-3.4). An association between presence of the APOE-epsilon4 allele and LOAD (relative risk 4.05; 95% confidence interval, 1.3-12.5) was observed. CONCLUSION: We could not confirm the relationship between the PS1 intron 8 polymorphism and LOAD in this collection of families.     

Interactions of galanin and morphine in the spinal antinociception in rats with mononeuropathy

The increased hind-paw withdrawal latency (HWL) to thermal stimulation and hind-paw withdrawal threshold (HWT) to mechanical stimulation induced by morphine were attenuated by intrathecal injection of 1 or 3 nmol, but not 0.3 nmol of the selective galanin antagonist galantide. The result indicated a possible interaction between galanin and opioids in the transmission of presumed nociceptive information in the spinal cord of rats with mononeuropathy.     

Chronic ophthalmoplegia with anti-GQ1b antibody

Anti-GQ1b antibodies are typically found in patients with the Miller Fisher syndrome, all of whom will have, by definition, acute ophthalmoplegia. The authors describe three patients with chronic ophthalmoplegia in the presence of persistently high titers of immunoglobulin G anti-GQ1b antibody detected in an ELISA, one of whom improved with immunotherapy. Anti-GQ1b antibodies may be associated with some cases of chronic ophthalmoplegia of unknown cause.     

Paraplegia episodes revealing tuberculous myelitis

A 38 year-old woman, without previous medical history, presented, since 1993, several paraplegic fits carrying herself progressively through to a severe paraplegia. Diagnoses successively proposed were spinal cord compressions by slipped discs, spinal cord infarct and multiple sclerosis. In November 1998, the patient presented back pain and fever. Spinal cord magnetic resonance imaging (MRI) revealed a mildly enlarged dorsal cord with signal abnormalities. The lesions were isointense on T1-weighted images, hyperintense on T2-weighted images and showed a ringlike contrast enhancement. A lumbar puncture showed a trouble cerebrospinal fluid (CSF) with leucocytes 600/mm(3) (85 p.100 polynuclear), protein 6.7 g/l, glucose 0.26 g/l, chloride 109 mmol/l. The patient was first treated with parenteral unspecific antibiotherapy. Microbiological studies of blood and CSF were negative. CSF examination with polymerase chain reaction (PCR) was positive for Mycobacterium tuberculosis. Clinical (pain and fever) symptoms and CSF abnormalities decreased after antituberculous treatment. However, paraparesis remain severe. Spinal tuberculous localizations often lead to diagnostic and therapeutic errors. Improvement of spinal cord MRI sequences and using of PCR technics in CSF would contribute to reduce these difficulties.     

Indications for early aspirin use in acute ischemic stroke : A combined analysis of 40 000 randomized patients from the chinese acute stroke trial and the international stroke trial. On behalf of the CAST and IST collaborative groups

BACKGROUND AND PURPOSE: Long-term daily aspirin is of benefit in the years after ischemic stroke, and 2 large randomized trials (the Chinese Acute Stroke Trial [CAST] and the International Stroke Trial [IST]), with 20 000 patients in each, have shown that starting daily aspirin promptly in patients with suspected acute ischemic stroke also reduces the immediate risk of further stroke or death in hospital and the overall risk of death or dependency. However, some uncertainty remains about the effects of early aspirin in particular categories of patient with acute stroke. METHODS: To assess the balance of benefits and risks of aspirin in particular categories of patient with acute stroke (eg, the elderly, those without a CT scan, or those with atrial fibrillation), a prospectively planned meta-analysis is presented of the data from 40 000 individual patients from both trials on events that occurred in the hospital during the scheduled treatment period (4 weeks in CAST, 2 weeks in IST), with 10 characteristics used to define 28 subgroups. This represents 99% of the worldwide evidence from randomized trials. RESULTS: There was a highly significant reduction of 7 per 1000 (SD 1) in recurrent ischemic stroke (320 [1.6%] aspirin versus 457 [2. 3%] control, 2P<0.000001) and a less clearly significant reduction of 4 (SD 2) per 1000 in death without further stroke (5.0% versus 5. 4%, 2P=0.05). Against these benefits, there was an increase of 2 (SD 1) per 1000 in hemorrhagic stroke or hemorrhagic transformation of the original infarct (1.0% versus 0.8%, 2P=0.07) and no apparent effect on further stroke of unknown cause (0.9% versus 0.9%). In total, therefore, there was a net decrease of 9 (SD 3) per 1000 in the overall risk of further stroke or death in hospital (8.2% versus 9.1%, 2P=0.001). For the reduction of one third in recurrent ischemic stroke, subgroup-specific analyses found no significant heterogeneity of the proportional benefit of aspirin (chi(2)(18)=20. 9, NS), even though the overall treatment effect (chi(2)(1)=24.8, 2P<0.000001) was sufficiently large for such subgroup analyses to be statistically informative. The absolute risk among control patients was similar in all 28 subgroups, so the absolute reduction of approximately 7 per 1000 in recurrent ischemic stroke does not differ substantially with respect to age, sex, level of consciousness, atrial fibrillation, CT findings, blood pressure, stroke subtype, or concomitant heparin use. There was no good evidence that the apparent decrease of approximately 4 per 1000 in death without further stroke was reversed in any subgroup or that in any subgroup the increase in hemorrhagic stroke was much larger than the overall average of approximately 2 per 1000. Finally, there was no significant heterogeneity between the reductions in the composite outcome of any further stroke or death (chi(2)(18)=16.5, NS). Among the 9000 patients (22%) randomized without a prior CT scan, aspirin appeared to be of net benefit with no unusual excess of hemorrhagic stroke; moreover, even among the 800 (2%) who had inadvertently been randomized after a hemorrhagic stroke, there was no evidence of net hazard (further stroke or death, 63 aspirin versus 67 control). CONCLUSIONS: Early aspirin is of benefit for a wide range of patients, and its prompt use should be routinely considered for all patients with suspected acute ischemic stroke, mainly to reduce the risk of early recurrence.     

Vertebral artery dissections: follow-up with magnetic resonance angiography and injection of gadolinium

Vertebral artery dissection is a frequent cause of ischemic stroke in young adults but time course of VA dissections remains poorly documented. Angiography was considered as the gold standard for the diagnosis. Recently, non-invasive methods have been developed such as helical CT and magnetic resonance angiography. The purpose of the study was to assess the reliability of a gadolinium-enhanced fast three dimensional (3D) magnetic resonance (MR) angiographic sequence to image vertebral arteries and to assess the long-term follow-up of vertebral artery (VA) dissections. Sixteen consecutive patients with 18 angiographically documented VA dissections were followed-up by gadolinium-enhanced 3D MR angiography and cervical T1-weighted MR imaging at a median delay of 22 months. Ten patients had MR imaging scan at the acute stage as well and nine had early follow-up angiography at a median delay of 3 months. MR angiography was evaluated in a consensus manner including image quality, presence of residual stenosis, luminal irregularities and occlusion. All patients clinically improved. Ten of 11 stenotic dissections returned to normality whereas one stenotic dissection progressed to occlusion. Two pseudoaneurysms detected on the initial angiography resolved spontaneously, one appeared only on a delayed MR angiographic scan and one was detected on early MR angiograms and finally resolved on a late one. Of the seven initially occluded VAs, five reopened with a hairline residual lumen in three. Contrast MR angiography is an interesting tool to assess the late course of VA dissections. Most lesions resolved spontaneously but persisting occlusion or pseudoaneurysm may be found in long term follow-up.     

Accumulation of insoluble alpha-synuclein in dementia with Lewy bodies

The alpha-synuclein (alpha SN) protein is thought to play a central role in the pathogenesis of neurodegenerative diseases where it aggregates to form intracellular inclusions. We have used Western blotting to examine the expression levels and solubility of alpha SN in brain homogenates from dementia with Lewy bodies (DLB), Parkinson's disease (PD), Alzheimer's disease (AD), and normal controls using samples from the parahippocampus/transentorhinal cortex. Compared to controls, DLB brains accumulate significantly greater amounts of sodium dodecyl sulfate (SDS)-soluble and SDS-insoluble alpha SN but levels of TBS-soluble alpha SN did not change. Levels of synaptophysin, a marker of synaptic integrity, were significantly lower in DLB cases than in normal aged controls regardless of whether concurrent changes of AD were present. This limbic synaptic dysfunction may contribute to cognitive impairment in DLB. Whether aggregated alpha SN is a cause or effect of the disease process in DLB and PD remains to be determined, but the presence of aggregated alpha SN is consistent with a pathogenesis similar to that associated with aggregates of Abeta amyloid in AD.     

Comparative study of quality of life between the Chinese and Japanese adolescent populations

Researchers from Japan, China and Singapore have initiated a collaborative project, with the aim of comparing adolescent quality of life (QOL) internationally. This study presents the primary results of the investigation conducted in Beijing, China, and Kobe, Japan. The 70-item Quality of Life Questionnaire for Adolescents (QOLQA) was developed and evaluated in Japan and China. In total, 1114 Japanese and 613 Chinese junior high school students, aged 12-15 years, completed the questionnaire. Chinese students scored significantly higher than the Japanese students in overall QOL scores and in most domains. For both groups, subjects had highest score in the independence domain and lowest in psychological domain. In terms of overall QOL score, Chinese male students ranked first, followed by Chinese girls, Japanese boys, and Japanese girls. In the Japanese group, a continuing decrease of QOL scores with age was observed without exception, but no such tendency was present in their Chinese counterparts. No parallel relationship was observed between the higher level of economic development and better quality of life. The results also suggest that mental health promotion should be a priority in improving overall quality of life of adolescents both in Japan and China.     

Evaluation of combined therapy with chemoembolization and irradiation for large hepatocellular carcinoma

The effects of combined transcatheter arterial chemoembolization (TACE) and radiotherapy in patients with large hepatocellular carcinoma (HCC) were analysed retrospectively. A total of 107 patients with large unresectable HCC was treated with TACE followed by external beam irradiation. The largest dimension of the tumours ranged from 5 cm to 18 cm. Acute effects, survival rates, toxicity and prognostic factors were analysed. Follow-up ranged from 4 months to 98 months (median 24 months). An objective response, i.e. reduction of tumour area greater than 50%, was achieved in 48.6% of cases. In 64.9% of the cases with increased alpha-feto protein (AFP) values, AFP level underwent a reduction of more than 25%. The cumulative survival rates at 1, 3 and 5 years were 59.4%, 28.4% and 15.8%, respectively (median survival 18 months). The combination therapy was generally well tolerated. Only two patients died from liver failure or variceal bleeding associated with therapy. The Cox proportional hazards model showed that the number of tumours and the irradiation dose were independent prognostic factors. The results indicate that combined TACE with radiotherapy is a promising therapeutic approach for large unresectable HCC. Prospective controlled trials to ascertain the real potential benefit of this approach are required.