Subjective Cognitive Complaints: Comparing the Relation between Self-Reported Versus Informant-Reported Subjective Cognitive Complaints and Cognitive Performances in Cognitively Unimpaired, Mild Cognitive Impairment and Populations with Dementia.

BACKGROUND: Subjective cognitive decline is proposed to be associated with future mild cognitive impairment and dementia. A better understanding of the roles of self-reported and informant-reported subjective cognitive complaints can provide a more delicate picture in dementia recognition and early diagnosis. OBJECTIVES: To evaluate the accuracy of self-reported and informant-reported subjective cognitive complaints and the relation of subjective cognitive complaints and neuropsychological function in cognitively unimpaired, mild cognitive impairment and populations with dementia. DESIGN: We conducted a cross-sectional survey and evaluate the relations between subjective cognitive complaint scores and cognitive function in the different diagnostic groups. SETTING: We recruited individuals diagnosed with cognitively unimpaired or mild cognitive impairment or dementia with Alzheimer's clinical syndrome from a memory clinic in a tertiary medical center in Taiwan. PARTICIPANTS: Participants, age greater than 50 years old, were enrolled in this study. Participants' informants were also enrolled for the cognitive questionnaire assessment. MEASUREMENTS: Participants' and informants' subjective cognitive complaint scores were collected based on a 12-item questionnaire. Neuropsychological assessments of global cognitive function, memory, language, executive function, visuospatial function and calculation were performed. The relations between subjective cognitive complaint scores and cognitive function in the different diagnostic groups were assessed by linear regression model. RESULTS: There were 1536 individuals and 1028 informants enrolled in this study. Self-reported subjective cognitive complaint scores from early and late mild cognitive impairment and dementia with Alzheimer's clinical syndrome participants showed no significant differences, but informants' subjective cognitive complaint scores showed a significant increase. Informant-reported subjective cognitive complaint scores related to neuropsychological tests in population with dementia. Neither self-reported nor informant-reported subjective cognitive complaint scores related to neuropsychological tests in cognitively unimpaired and mild cognitive impairment populations. CONCLUSIONS: Self-reported subjective cognitive complaints alone may not be sufficient to demonstrate clinical significance in different stages of cognitive impairment. Incorporating informant-reported subjective cognitive complaints, along with considering individual's anxiety and depressive status, are crucial in assessing cognitive statuses in clinical practice.

Predictive Utility of Plasma Amyloid and Tau for Cognitive Decline in Cognitively Normal Adults.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease affecting mostly elderly adults. Recent diagnostic criteria for AD recommend the use of imaging and/or cerebrospinal fluid (CSF) biomarkers together with clinical presentation for a more persuasive diagnosis. The invasiveness and expense of such examinations have led to the search for blood-based biomarkers. The plasma levels of amyloid-ß (Aß) protein and tau peptides have been found to correlate with CSF levels and imaging findings in patients with AD. This study was conducted to explore the predictive utility of plasma Aß1-42 and total tau (t-tau) levels for cognitive decline in healthy adults. METHODS: In this prospective longitudinal study, we enrolled adults aged ≥ 50 years with normal cognition at Taipei Veterans General Hospital from November 2016 to April 2019. Blood samples were collected on recruitment, and plasma Aß1-42 and t-tau levels were quantified through immunomagnetic reduction. Thorough neurophysiological assessment was performed at baseline and at the annual follow-up visit. The participants were divided into two groups according to cognitive decline. The predictive utility of Aß1-42 and t-tau levels was evaluated by receiver operating characteristic curve analysis. RESULTS: Of 60 participants recruited, seven participants progressed to mild cognitive impairment and 53 retained normal cognition on follow-up (average 1.07 ± 0.2 years). The baseline levels of plasma biomarkers (Aß1-42, t-tau, and Aß1-42 × t-tau) were significantly higher in the progressive than in the stable group (p = 0.005, p = 0.007, and p = 0.005, respectively). Higher plasma biomarker levels (Aß1-42 ≥ 16.96 pg/ml and Aß1-42 × t-tau ≥ 382 pg2/ml2) predicted more cognitive decline on annual follow-up visits. CONCLUSION: Plasma Aß1-42 and t-tau levels have predictive utility for cognitive decline, even in subjects with normal cognition. Higher baseline plasma Aß1-42 and t-tau levels may indicate a higher risk of cognitive decline in cognitively normal adults.

Probiotic Escherichia coli Nissle inhibits IL-6 and MAPK-mediated cardiac hypertrophy during STZ-induced diabetes in rats.

Escherichia coli Nissle (EcN), a probiotic bacterium protects against several disorders. Multiple reports have studied the pathways involved in cardiac hypertrophy. However, the effects of probiotic EcN against diabetes-induced cardiac hypertrophy remain to be understood. We administered five weeks old Wistar male (271±19.4 g body weight) streptozotocin-induced diabetic rats with 109 cfu of EcN via oral gavage every day for 24 days followed by subjecting the rats to echocardiography to analyse the cardiac parameters. Overexpressed interleukin (IL)-6 induced the MEK5/ERK5, JAK2/STAT3, and MAPK signalling cascades in streptozotocin-induced diabetic rats. Further, the upregulation of calcineurin, NFATc3, and p-GATA4 led to the elevation of hypertrophy markers, such as atrial and B-type natriuretic peptides. In contrast, diabetic rats supplemented with probiotic EcN exhibited significant downregulated IL-6. Moreover, the MEK5/ERK5 and JAK2/STAT3 cascades involved during eccentric hypertrophy and MAPK signalling, including phosphorylated MEK, ERK, JNK, and p-38, were significantly attenuated in diabetic rats after supplementation of EcN. Western blotting and immunofluorescence revealed the significant downregulation of NFATc3 and downstream mediators, thereby resulting in the impairment of cardiac hypertrophy. Taken together, the findings demonstrate that supplementing probiotic EcN has the potential to show cardioprotective effects by inhibiting diabetes-induced cardiomyopathies.

Decreased expression of SorCS1 in colorectal cancer: An independent predictor of poor prognosis.

Previously, we identified that sortilin related VPS10 domain containing receptor 1 (SorCS1) was hypermethylated in colorectal cancer (CRC) tissues. Here, we aimed to investigate the association between CRC and SorCS1. DNA methylation was determined by methylation-specific polymerase chain reaction (MSP) or quantitative real-time methylation analysis (MethyLight). Colorectal cancer tissue specimens from 239 patients that had undergone surgical treatment were evaluated using immunohistochemistry (IHC) analysis for the expression of SorCS1 and correlated with clinicopathological variables and prognosis. We found that SorCS1 was hypermethylated in CRC cell lines and 67.5% (27/40) CRC tumor tissues. The loss of SorCS1 mRNA (p<0.001) and protein expression (p=0.033) were highly correlated with promoter methylation. In addition, SorCS1 expression was significantly increased in younger patients (p=0.006), low CEA level (p<0.001) and pT1-2 stage (p=0.005). Survival analysis revealed that decreased expression of SorCS1 was an independent factor for predicting the increased risk of recurrence (p=0.024) and poor overall survival (p=0.006). Subgroup analysis for CEA level, pT and pN classifications showed that SorCS1 retained its stratified significance only in patients with low CEA level, pT3-4 tumors and pN1-2 lymph node status. Our findings suggest that SorCS1 is epigenetically inactivated in a substantial fraction of CRC, and its expression may be a promising prognostic factor in CRC patients.

Development and Validation of a Tool to Screen for Cognitive Frailty among Community-Dwelling Elders.

OBJECTIVES: Reciprocal age-related impairments in physical and cognitive functioning have been termed 'cognitive frailty', which is associated with adverse health outcomes and is a potential target for preventing or delaying the onset of disability in older people. However, cognitive frailty as currently defined is challenging to diagnose. To facilitate earlier diagnosis and intervention, we conducted this study to develop and validate a simple evidence-based instrument to identify community-dwelling elders at risk of cognitive frailty. DESIGN: Retrospective analyses of data from the I-Lan Longitudinal Aging Study (ILAS) to develop a prediction model, and from the Longitudinal Aging Study of Taipei (LAST) for external validation. SETTING: Community-dwelling adults from Taipei City, New Taipei City and Yilan (I-Lan) County, Taiwan. PARTICIPANTS: 1271 community residents ≥65 years old, without impaired global cognition or dependency for activities of daily living/instrumental activities of daily living. MEASUREMENTS: Demographic characteristics, anthropometric measurements, medical history, Mini-Mental State Examination, Montreal Cognitive Assessment, Functional Autonomy Measuring System, Functional Assessment Staging Test, Center for Epidemiologic Studies Depression Scale, handgrip strength, 6-metre walk speed. METHODS: Baseline characteristics of groups with/without cognitive frailty were analyzed and factors differing significantly in univariate analysis input to binary logistic regression to develop a cognitive frailty risk (CFR) score. RESULTS: The prevalence of cognitive frailty was 15.8% overall; ILAS 21.4%, LAST 8.4%. Predictors of CFR comprised: age ≥75 years; female sex; waist circumference ≥90 cm (male), ≥80 cm (female); calf circumference <33 cm (male), <32 cm (female); memory deficits; and diabetes mellitus. CFR ≥5/14 had sensitivity of 70%, specificity of 60%, and predictive accuracy of 72%. CONCLUSIONS: A CFR score based on simple history-taking and anthropometric measurements integrates age, sex, cardiometabolic risk, memory deficits, sarcopenia, and nutrition, with validated predictive accuracy, and could be performed easily in community settings to identify seniors with cognitive frailty for appropriate interventions.

Modest Overweight and Healthy Dietary Habits Reduce Risk of Dementia: A Nationwide Survey in Taiwan.

BACKGROUND: Evidence of the associations of dietary habits and body mass index with dementia is inconsistent and limited in East Asian countries. OBJECTIVE: We aim to explore the associations of dietary habits and body mass index with the odds of dementia. DESIGN: Cross-sectional observational study. SETTING: A nationwide, population-based, door-to-door, in-person survey. PARTICIPANTS: Selected by computerized random sampling from all 19 counties in Taiwan. MEASUREMENT: Diagnosis of dementia using the criteria recommended by the National Institute on Aging-Alzheimer's Association. Lifestyle factors, dietary habits and demographic data were compared between normal subjects and participants with dementia. RESULTS: A total of 10432 residents were assessed, among whom 2049 were classified as having a mild cognitive impairment (MCI), 929 were diagnosed with dementia, and 7035 were without dementia or MCI. After adjustment for age, gender, education, body mass index (BMI), dietary habits, habitual exercises and co-morbidities, including hypertension, diabetes and cerebrovascular diseases, we found inverse associations of dementia with the consumption of fish (OR 0.62, 95% CI 0.41-0.94), vegetables (OR 0.35, 95% CI 0.13-0.95), coffee (OR 0.59, 95% CI 0.35-0.97), green tea (OR 0.51, 95% CI 0.34-0.75) and other types of tea (OR 0.41, 95% CI 0.28-0.60). There was no association between dementia and fruit consumption. Compared with people who had a normal BMI (18 < BMI <= 24), older overweight people (24 < BMI <=30) had a reduced risk of dementia with an adjusted OR of 0.77 (95% CI 0.61-0.96). CONCLUSIONS: Our study provides preliminary evidence that suggests that the consumption of fish, vegetables, tea, and coffee has potential benefits against dementia in East Asian population. Being modestly overweight (nadir risk at BMI = 25) in late life was associated with decreased odds of dementia. The benefit of fruits may be offset by their high sugar content.

Intervention versus Aggressive Medical Therapy for Cognition in Severe Asymptomatic Carotid Stenosis.

BACKGROUND AND PURPOSE: Asymptomatic carotid stenosis of ≥70% increases the incidence of microembolism and/or chronic hypoperfusion, which may consequently impair neurocognition and brain connections. We sought controlled evidence for any cognitive benefit of aggressive medical therapy and combined carotid revascularization. MATERIALS AND METHODS: Patients with asymptomatic, unilateral, ≧70% stenosis of the extracranial ICA chose either aggressive medical therapy alone or in combination with carotid artery stent placement in this nonrandomized controlled study. They were examined with a battery of neuropsychological tests, structural MR imaging, DTI, and resting-state fMRI before and 3 months after treatment. RESULTS: Forty patients were included with 15 in the medical group and 25 in the stent-placement group. Among them, 13 and 21 in the respective groups completed neuroimaging follow-up. The baseline characteristics and the changes in cognitive performance during 3 months showed no differences between treatment groups. Nevertheless, compared with the medical group, the stent-placement group showed subjective dizziness alleviation (P = .045) and a small increase in fractional anisotropy at the splenium of the corpus callosum and the posterior periventricular white matter ipsilateral to carotid artery stent placement. Moreover, only the stent-placement group showed interval improvement in immediate memory and visuospatial performance, which was accompanied by an increase of functional connectivity at the insular cortex of the dorsal attention network and the medial prefrontal cortex of the default mode network. CONCLUSIONS: Both aggressive medical therapy alone and combined carotid revascularization in ≧70% asymptomatic carotid stenosis similarly preserved cognition during 3-month follow-up, though the latter had the potential for dizziness alleviation and cognitive and connectivity enhancement.

Sustainable complete remission in recurrence yolk sac tumor patient treated with tandem high-dose chemotherapy and autologous stem cell.

A 21-year-old lady diagnosed with Stage 3 ovarian yolk sac tumor (YST) underwent primary cytoreductive fertility sparing surgery, followed by conventional courses of platinum-based chemotherapy and etoposide. Recurrence at cul-da-sac was noted after a short period of remission and secondary debulking performed followed by four cycles of conventional chemotherapy. The patient's disease progressed despite courses of treatments. A joint team management including a hematologist was commenced following the failure of conventional chemotherapies. Two cycles of high-dose chemotherapy (HDCT) with ifosfamide/cisplatin/etoposide (ICE) regimen, followed by autologous stem cell transplantation (ASCT) were given. With this salvage treatment, she remained in complete remission and disease-free for more than 30 months, while maintaining her reproductive function. These approaches appear to be effective as a salvage treatment in selected cases of patients with ovarian germ cell tumor, especially those who failed primary conventional chemotherapy.

A comparison study of detecting gold nanorods in living cells with confocal reflectance microscopy and two-photon fluorescence microscopy.

Two-photon fluorescence microscopy and confocal reflectance microscopy were compared to detect intracellular gold nanorods in rat basophilic leukaemia cells. The two-photon photoluminescence images of gold nanorods were acquired by an 800 nm fs laser with the power of milliwatts. The advantages of the obtained two-photon photoluminescence images are high spatial resolution and reduced background. However, a remarkable photothermal effect on cells was seen after 30 times continuous scanning of the femto-second laser, potentially affecting the subcellular localization pattern of the nanorods. In the case of confocal reflectance microscopy the images of gold nanorods can be obtained with the power of light source as low as microwatts, thus avoiding the photothermal effect, but the resolution of such images is reduced. We have noted that confocal reflectance images of cellular gold nanorods achieved with 50 microW 800 nm fs have a relatively poor resolution, whereas the 50 microW 488 nm CW laser can acquire reasonably satisfactory 3D reflectance images with improved resolution because of its shorter wavelength. Therefore, confocal reflectance microscopy may also be a suitable means to image intracellular gold nanorods with the advantage of reduced photothermal effect.

Microscopic polyangiitis presenting with capsular warning syndrome and subsequent stroke.

A 55-year-old man developed ischemic stroke after three episodes of transient dysarthria and left hemiplegia, a typical manifestation of capsular warning syndrome. Magnetic resonance imaging of the brain showed bilateral basal ganglionic infarction. The patient had no significant risk of stroke. However, the systemic manifestations, an elevated titer of perinuclear anti-neutrophilic cytoplasmic antibody and a skin biopsy revealing leukocytoclastic venulitis confirmed the undrlying microscopic polyangiitis.

Disseminated xanthogranulomas associated with adult T-cell leukaemia/lymphoma: a case report and review the association of haematologic malignancies.

Xanthogranuloma (XG) is rarely observed in adults and has been reported to be associated with chronic myelogenous leukaemia (CML) and/or neurofibromatosis type 1 (NF1). A 68-year-old woman with adult T-cell leukaemia/lymphoma (ATLL) gradually developed disseminated XGs over the 3 years since disease onset. Histopathological examination of a skin biopsy revealed the presence of histiocytes in the dermis with a few Touton giant cells admixed with lymphoid cells. The lesions of XGs persisted despite chemotherapy with prednisolone and chlorambucil for her ATLL. This is the first report of disseminated XGs associated with ATLL. The association of disseminated XGs with haematologic malignancies was reviewed and the possible pathogenesis of this association will be discussed.

Enhancement of intracellular delivery of CdTe quantum dots (QDs) to living cells by Tat conjugation.

Quantum dots (QDs), as novel fluorescence probes, have shown a great potential for bio-molecular labeling and cellular imaging. To stain cellular targets, the sufficient intracellular delivery of QDs is required. In this work the tat, a typical membrane-permeable carrier peptide, was conjugated with thiol-capped CdTe QDs to form CdTe Tat-QDs, and the intracellular deliveries of CdTe QDs or CdTe Tat-QDs were compared in human hepatocellular carcinoma (QGY) cells and human breast cancer (MCF7) cells in vitro by means of confocal laser scanning microscopy. Added into the cell dishes, both QDs and Tat-QDs adhered to the outer leaflet of the plasma membrane of cells within a few minutes, but the binding amount of Tat-QDs was obviously higher than that of QDs. Then both QDs and Tat-QDs can penetrate into cells, and their cellular contents increased with incubation time but both saturated after 3 hours incubation. However the cellular levels of Tat-QDs were higher than those of QDs, with the ratio of 2.1 (+/-0.3) times in QGY cells and 1.5 (+/-0.2) times in MCF7 cells, demonstrating the enhancing effect of Tat conjugation on the intracellular delivery of QDs.

Refractive index measurement for biomaterial samples by total internal reflection.

The refractive index of biological tissue is a fundamental parameter in applications of optical diagnosis and laser treatments. In the present work, the refractive indices and thermo-optic coefficients of some basic biomaterials, such as blood plasma, haemoglobin solution and lipid membrane, were studied by the method of total internal reflection at the wavelengths of 532 and 632.8 nm that are the most frequently used laser wavelengths in the biomedical field. The effects of the sample concentration and the temperature on refractive index were measured, and empirical relationships were summarized, accompanied by a theoretical explanation based on molecular polarization theory. The results provide some fundamental data for the refractive indices of these biomaterials under variant conditions, and also demonstrate that the total internal reflection method is a feasible and reliable way to measure the refractive indices of biological samples.

AML patients with CEBPalpha mutations mostly retain identical mutant patterns but frequently change in allelic distribution at relapse: a comparative analysis on paired diagnosis and relapse samples.

The roles of CEBPalpha mutations and its cooperating mutations in the relapse of acute myeloid leukemia (AML) are not clear. CEBPalpha mutations were analyzed on 149 patients with de novo AML at both diagnosis and relapse. Twenty-two patients (14.8%) had the mutations at diagnosis, two patients had N-terminal nonsense mutations alone, one had homozygous inframe duplication at the bZIP domain, and 19 patients had both N-terminal and bZIP mutations. Twenty patients relapsed with identical mutant patterns, two lost CEBPalpha mutations and none acquired the mutations at relapse. Cloning analysis showed that the N-terminal and C-terminal mutations occurred on separate cloned alleles and also on the same alleles in most of the diagnosis and relapse samples. Losing one of the two or more mutations on the same allele or acquiring the other mutation on the allele original carrying single mutation were observed not infrequently in the paired samples analyzed. Seven patients with CEBPalpha mutations had cooperating mutations with FLT3/ITD, FLT3/TKD or N-ras but not K-ras mutations. Our study showed that 91% of de novo AML harboring CEBPalpha mutations at diagnosis retained the identical mutant patterns but frequently changed in the allelic distribution at relapse.

Characterization of fusion partner genes in 114 patients with de novo acute myeloid leukemia and MLL rearrangement.

The fusion transcripts of MLL rearrangement [MLL(+)] in acute myeloid leukemia (AML) and their clinicohematologic correlation have not be well characterized in the previous studies. We used Southern blot analysis to screen MLL(+) in de novo AML. Reverse transcriptase-polymerase chain reaction was used to detect the common MLL fusion transcripts. cDNA panhandle PCR was used to identify infrequent or unknown MLL partner genes. MLL(+) was identified in 114 (98 adults) of 988 AML patients. MLL fusion transcripts comprised of 63 partial tandem duplication of MLL (MLL-PTD), 14 MLL-AF9, 9 MLL-AF10, 9 MLL-ELL, 8 MLL-AF6, 4 MLL-ENL and one each of MLL-AF1, MLL-AF4, MLL-MSF, MLL-LCX, MLL-LARG, MLL-SEPT6 and MLL-CBL. The frequency of MLL-PTD was 7.1% in adults and 0.9% in children (P<0.001). 11q23 abnormalities were detected in 64% of MLL/t11q23 and in none of MLL-PTD by conventional cytogenetics. There were no differences in remission rate, event-free survival and overall survival between adult MLL-PTD and MLL/t11q23 groups. Adult patients had a significantly poorer outcome than children. The present study showed that cDNA panhandle PCR can identify all rare or novel MLL partner genes. MLL-PTD was rare in childhood AML. MLL(+) adults had a poor outcome with no difference in survival between MLL-PTD and MLL/t11q23 groups.

Prediction of Alzheimer's disease in mild cognitive impairment: a prospective study in Taiwan.

The relationship between apolipoprotein E (ApoE) and clinical manifestations of mild cognitive impairment (MCI) has not been investigated in non-Caucasian populations. This prospective study was conducted in an ethnic Chinese population to evaluate the correlations of ApoE genotype, cognitive performance, medial temporal structure volumes, and clinical outcome in amnestic MCI. Twenty normal elders, 58 MCI, and 20 mild Alzheimer's disease (AD) patients received neuropsychological, MRI, and ApoE genotype assessments at baseline. Patients with MCI had intermediate cognitive performance and hippocampal volumes between those in normal and AD groups. In each diagnostic group, epsilon4 carriers (E4+) consistently had smaller hippocampal volume than non-carriers (E4-) did. Nineteen MCI subjects (32.7%) converted to AD during the 3-year study period. Compared with MCI non-converters and E4- MCI converters, E4+ MCI converters had the smallest hippocampal volume. However, epsilon4 was not a predictor for AD. Both cognitive performance and hippocampal volume were predictive for progression to AD. However, stepwise Cox regression model integrating both neuropsychological and radiological variables showed that global cognitive performance was the only significant predictor for AD. A poor global cognitive score may be more crucial than a small hippocampal volume in the prediction of AD.

Cholinesterase inhibitor affects the amyloid precursor protein isoforms in patients with Alzheimer's disease.

An altered platelet ratio of amyloid precursor protein (APP) isoforms might be a diagnostic, predictive, or therapeutic marker for Alzheimer's disease (AD). Our purpose was to test the hypothesis that this ratio might serve as a therapeutic marker for AD patients treated with the cholinesterase inhibitor, galantamine. Thirty-nine patients (mean age 76.6 +/- 9.4 years) with AD were treated with galantamine for 12 weeks. Patients were evaluated at baseline, 4 and 12 weeks by cognitive testing along with a determination of their platelet APP isoform ratio. Western blotting was performed to calculate the APP isoform ratio. At the end of the treatment, cognitive scores significantly improved, and the ratio of the high-molecular-weight (130 kDa) isoform to the low-molecular-weight (110-106 kDa) isoforms increased. These results suggest that cholinesterase inhibition might be involved in APP processing.

Estrogen-metabolizing gene COMT polymorphism synergistic APOE epsilon4 allele increases the risk of Alzheimer disease.

Alzheimer disease (AD) is a polygenic multifactorial disorder. Several studies suggested that the neuroprotective effect of estrogen was based on an APOE-dependent mechanism. The goals of the current study were to determine if the genes involved in estrogen metabolism were linked to the risk of AD and find out if there was an interaction between estrogen-metabolizing gene polymorphisms and the APOE epsilon4 allele in the risk of prevalent AD. We investigated 66 patients with AD and 86 age- and gender-matched normal subjects. The polymorphisms of APOE and estrogen-metabolizing genes CYP17, CYP1A1 and COMT were examined. No association was found between each estrogen-metabolizing gene polymorphism and AD. However, the COMT HH genotype and APOE epsilon4 allele had a synergistic effect on the risk of AD. Taking subjects with epsilon4-epsilon4-/HH- as reference, the risk of developing AD in subjects with one epsilon4 allele (epsilon4+epsilon4-/HH-) was 2.6 (95% confidence interval, CI, 0.7- 9.1); however, the risk in subjects with both HH and one epsilon4 (epsilon4+epsilon4-/HH+) increased to 3.6 (95% CI 1.2-10.6). The subjects with homozygous epsilon4 still had the highest risk in developing AD (odds ratio 6.6, 95% CI 0.6-69.6). The p value of the linear trend test for this regression model was 0.004. It is possible that a high metabolism of estrogen by COMT may have reduced the protective effect of estrogen in AD. Further studies to clarify this interaction may improve our understanding of the generic risks for AD.

Acute leukaemia in chronic hepatitis B patients with lamivudine therapy.

Extensive clinical data have shown that lamivudine is an effective and safe drug for patients with chronic hepatitis B virus infection. No significant serious side effect has been reported. Four hundred and forty-eight patients with chronic hepatitis B, treated with lamivudine for more than 6 months, were closely monitored. Two patients developed acute myeloid leukaemia during or after lamivudine therapy. The first case developed acute myeloid leukaemia, 1 year after stopping lamivudine therapy, when A529T mutant HBV-DNA was still detectable. The second case achieved complete virological response but suffered from acute myeloid leukaemia during the ninth month of lamivudine treatment. D553N mutant hepatitis B virus was detected in granulocytes of her peripheral blood. Based on our lamivudine therapy data, the calculated incidence of acute myeloid leukaemia in patients during or after lamivudine therapy was higher in males and females than that of the general population. Whether lamivudine-selected viral mutations have enhanced activity/production of transcriptional transactivator and thereby increased the chance of leukaemic transformation of haematopoietic progenitor cells deserves further investigation.