Plasma Total Homocysteine Levels are not Associated with Medial Temporal Lobe Atrophy, but with White Matter Changes in Alzheimer's Disease

Background and purpose

Elevated plasma total homocysteine (tHcy) levels are reported to be associated with an increased risk of Alzheimer''s disease (AD). However, the mechanism by which homocysteine contributes to the pathogenesis of AD is as yet unknown. The aim of this study was to elucidate the relationship between white matter changes (WMC) and medial temporal lobe atrophy (MTA) on brain magnetic resonance imaging (MRI), and plasma levels of tHcy in AD patients.

Methods

Seventy-two patients with a clinical diagnosis of probable AD were recruited to the study. Plasma tHcy levels, vascular risk factors, and WMC and MTA on brain MRI were evaluated in all patients. The AD patients were classified into two groups: those with no or minimal WMC (69.2±8.8 years, mean±SD, n=36) and those with moderate-to-severe WMC (74.6±4.6 years, n=36) on brain MRI.

Results

In a univariate logistic regression analysis, the risk of moderate-to-severe WMC in AD was significantly associated with increasing age, female gender, lower education level, hypertension, high plasma tHcy levels, and lower Mini-Mental State Examination (MMSE) score. Multivariate logistic regression analysis revealed only high plasma tHcy as the independent and significant risk factor for moderate-to-severe WMC [odds ratio (OR; adjusted for age, gender, education level, MMSE score, and hypertension comparing the top tertile - tHcy levels ≥12.9 µmol/L - with the bottom tertile - tHcy levels ≤9.4 µmol/L)=7.35; 95% confidence interval, confidence interval=1.36-39.84; p=0.02], and age as a borderline significant risk factor (OR=1.08, 95% CI=0.99-1.19, p=0.09) in AD patients. Plasma tHcy levels were not correlated significantly with either right or left MTA.

Conclusions

Our results suggest that the vascular pathway mediates the association between elevated plasma tHcy levels and AD.     

Post-Laminectomy Kyphosis in Patients with Cervical Ossification of the Posterior Longitudinal Ligament : Does It Cause Neurological Deterioration?

Objective

Total laminectomy (TL) is an effective surgical technique for the treatment of cervical ossification of the posterior longitudinal ligament (OPLL) along multiple levels. However, kyphosis and probable neurological deterioration have been frequently reported after laminectomy. We analyzed the changes in the cervical curvature after TL and subsequent changes in neurological status.

Methods

We retrospectively reviewed the records of 14 patients who underwent TL for the treatment of cervical OPLL between Jan. 1998 and Dec. 2003. TL was selected according to the previously determined criteria. The curvature of the cervical spine was visualized on a lateral cervical spine X-ray and measured using Ishihara''s Curvature Index (CI) before the operation and at the last follow-up examination. Perioperative neurological status was estimated using the modified Japanese Orthopedic Association score and the Improvement Rate (IR) at the same time as the images were evaluated.

Results

The mean age of the patients was 57 years, the male/female ratio was 10:4, and the mean follow-up period was 41 months. The mean number of OPLL was 4.9, and the mean number of operated levels was also 4.9. The CI decreased after TL (p=0.002), which was indicative of a kyphotic change. However, this kyphotic change showed no correlation with the length of the follow-up period, number of operated levels and preoperative CI. Neurological examination at the last follow-up showed an improved neurological status in all patients (p=0.001). There was no neurological deterioration in any case during the follow-up period. Moreover, there was no correlation between IR and the degree of kyphotic change. Postoperative complications, such as C5 radiculopathy and epidural bleeding, resolved spontaneously without neurological sequelae.

Conclusion

Kyphotic change was observed in all but one patient who underwent TL for the treatment of cervical OPLL. However, we did not find any contributing factors to kyphosis or evidence of postoperative neurological deterioration.     

Evaluation of the NucliSens EasyQ HIV-1 v1.1 and RealTime HIV-1 kits for quantitation of HIV-1 RNA in plasma

Human immunodeficiency virus type-1 (HIV-1) RNA viral load is an important biomarker to evaluate the therapeutic efficacy of antiretroviral drugs and to monitor disease progression in HIV-infected individuals. We compared HIV-1 RNA quantitation between two different kits, the NucliSens EasyQ^® HIV-1 v1.1 (EasyQ, bioMérieux) and RealTime HIV-1 (RealTime, Abbott), using HIV-1 RNA quality control (QC) materials, cell-cultivated viruses, and the plasma samples of 104 patients with HIV. Correlation between the two kits for HIV RNA-1 quantitation with clinical samples was high (R = 0.91). Based on results obtained with quality control standards, the reproducibility of the RealTime kit was higher than the EasyQ kit: the viral load value and coefficient of variation of each kit was 4.11 ± 0.136 and 3.3% for EasyQ and 3.55 ± 0.042 and 1.2% for RealTime, respectively (P < 0.002).This is the first comparative analysis of the detection limit and reproducibility of two different quantitation kits using clinical plasma samples from Korean HIV-1-infected patients. It will serve a useful reference to determine correction values for each HIV-1 RNA quantitation kits and to choose an appropriate assay kit for each laboratory.     

The correlation between human adipose-derived stem cells differentiation and cell adhesion mechanism

In recent years, research in the areas of stem cells has dramatically increased, including studies of cellular adhesion to a substrate. We sought to determine the adhesive properties of human adipose-derived stem cells (hASCs) for extracellular matrix proteins. The adhesion of hASCs to collagens and laminin was completely inhibited by a monoclonal antibody, Mab 2253, which binds to the β1 integrin subunit. These data indicate that hASC adhesion to collagens and laminin was exclusively mediated by an integrin. Cell adhesion on fibronectin (Fn) was inhibited by the heparin-binding peptide (HBP) in the presence of Mab 2253, but not by either Mab 2253 or HBP alone. These results indicate that both the β1 subunit and the heparan sulfate proteoglycan participated in the cell adhesion to Fn. Microscopic views showed extensive spreading of hASCs cultured on Fn, whereas the cells maintained a round shape when cultured on a heparin-binding domain (HBD) substrate. hASCs differentiated into adipocytes, which stained positive for lipid vacuoles by Oil Red-O analysis, more readily on HBD substrate than on FN substrate. These results suggest that hASCs have an adhesion mechanism for the HBD of Fn and hASC morphology is controlled by the adhesion mechanism and strongly correlated with adipogenic differentiation.     

Structural changes in the acromioclavicular joint measured by ultrasonography during provocative tests

The acromioclavicular joint (ACJ) is a common source of pain and disability. Several provocative tests are used to diagnose ACJ lesions. The aim of this study was to evaluate anatomic changes of the ACJ using dynamic ultrasonography during provocative tests. Eighty ACJs of 40 healthy volunteers were subjected to dynamic ultrasonographic examinations. Examinations were performed in a resting position and during passive external rotation, cross body adduction, and active compression testing. Deep joint space distance and capsule displacement were measured ultrasonographically. Mean deep joint space distances during cross body adduction (6.4 ± 1.6 mm) and active compression (6.6 ± 1.8 mm) testing were significantly smaller than during passive external rotation testing (7.7 ± 1.7 mm, P < 0.01) or rest (8.1 ± 1.8 mm, P < 0.01). Mean capsule displacements during active compression (3.5 ± 0.8 mm) and cross body adduction (3.4 ± 0.7 mm) testing were significantly greater than those during passive external rotation testing (2.9 ± 0.7 mm, P < 0.01) or rest (2.5 ± 0.7 mm, P < 0.01). Dynamic ultrasonography revealed that the cross body adduction and active compression tests applied more stress to the ACJ than the passive external rotation test, which suggests that these two tests are likely to be more useful provocative tests for the diagnosis of ACJ lesions. Furthermore, the dynamic properties of ultrasonography could be used to estimate the suitability and validity of provocative tests in other musculoskeletal diseases. Clin. Anat. 22:580–585, 2009. © 2009 Wiley‐Liss, Inc.     

Is the early cyclosporine A level predictive of the outcome of immunosuppressive therapy in severe aplastic anemia?

Immunosuppressive therapy (IST) has provided an alternative treatment option for cure of aplastic anemia patients who cannot receive bone marrow transplantation. Although there have been many recent studies on the efficacy of antithymoglobulin (ATG) combined with cyclosporine A (CsA), there is no data on the correlation between the variability of CsA levels and the response to IST. Therefore, we retrospectively assessed the factors associated with IST efficacy in patients with acquired severe aplastic anemia (SAA). Sixty‐six patients were treated with ATG combined with CsA for 6 months. In the response group, the CsA levels were increased rapidly to more than 200 ng/mL within the first 2 wk after starting the IST. However, the non‐response group had a pattern of slower increase of the CsA levels. The CsA levels, during the first and second week of treatment with IST, were significantly different in the responders and non‐responders. The factors predictive of response to IST and survival were analyzed. The univariate analysis showed that a younger age at the initiation of IST, a high absolute neutrophil count prior to starting IST, a short interval between the diagnosis and initiation of IST, and high CsA levels during the first and second week of IST treatment were positively associated with the response rate and overall survival. The multivariate analysis showed that these four factors were independent factors associated with a longer patient survival. A high response rate was associated with a short interval between diagnosis and initiation of IST as well as high CsA levels during the first and second week of IST. Therefore, early intensification of CsA levels might improve patient outcome.     

Simple technique for the rescue and refixation of a partially disenclavated retropupillary iris claw intraocular lens

AIM: To describe and compare pathologic findings in eyes enucleated after superselective ophthalmic arterial chemotherapy (SOAC) or SOAC with intravenous chemotherapy (IVC) for retinoblastoma. METHODS: Medical records between January 1st, 2014 and June 31st, 2017 were retrospectively analyzed, and pathologic findings were recorded. This study included 36 eyes from 22 (61.1%) male and 14 (38.9%) female patients. Nineteen of 36 (52.8%) eyes received SOAC (mean=3, range=1-7) as primary treatment, and 17 of 36 (47.2%) eyes received SOAC (mean=3.7, range=1-10) after IVC (mean=6.1, range=2-11). Tumor extension including choroidal invasion (n=9, 25%), optic nerve invasion (n=5, 13.9%) and anterior segment invasion (n=5, 13.9%) were recorded. RESULTS: Histopathologic evidence of ischemic damage in the retina and choroid was found in 28 (77.8%) eyes. Thrombosed blood vessels were identified in 9 (25%) eyes, including orbital artery in the retrobulbar orbit (n=1), intrascleral vessels (n=4), and chorioretinal vessels (n=6). Fibrotic changes were found in extraocular muscles (n=5, 13.9%) and optic nerve (n=5, 13.9%). Varying degrees of scleral degeneration were found in all eyes. In statistical analysis, there was no significant difference in clinical and pathologic changes between SOAC group and SOAC with IVC group except for optic nerve invasion (P=0.047). CONCLUSION: SOAC for retinoblastoma can result in ocular toxicity, and SOAC with IVC did not increase the toxicity but reduced the incidence of optic nerve invasion.     

Inhibition of endotoxin-induced activation of the coagulation and fibrinolytic pathways using a recombinant endotoxin-binding protein (rBPI23)

A recombinant endotoxin-neutralizing protein, rBPI23, was shown to partially prevent endotoxin-induced activation of the fibrinolytic and coagulation systems in experimental endotoxemia in humans. In a placebo- controlled, blinded crossover study, eight volunteers were challenged twice with an intravenous bolus injection of endotoxin (40 EU/kg of body weight) and concurrently received either rBPI23 (1 mg/kg) or placebo (human serum albumin, 0.2 mg/kg). rBPI23 treatment significantly lowered the endotoxin-induced fibrinolytic response, ie, reduced the release of tissue-type plasminogen activator, urokinase- type plasminogen activator, plasminogen activator inhibitor antigen, and complex formation of plasmin alpha 2-antiplasmin (P = .0078 for each). Plasminogen activator inhibitor activity was also reduced, but not significantly according to the Hochberg method (P = .0304). The endotoxin-induced activation of the procoagulant state as reflected by increase in F1 + 2 fragments and TAT complexes was blunted by rBPI23 infusion (P = .0391 [not significant according to the Hochberg method] and .0078, respectively). These results indicate that rBPI23 is capable of reducing both the activation of the fibrinolytic and the coagulation systems after low-dose endotoxin infusion in humans.