Homocysteine,depression and cognitive function in older adults

Background

Depression and high total plasma homocysteine (tHcy) are independently associated with cognitive impairment in older adults. We designed this study to determine if high tHcy is a mediator of cognitive performance in older adults with major depression.

Methods

We recruited 358 community-dwelling older adults experiencing depressive symptoms, 236 (65.9%) of who met DSM-IV-TR criteria for major depression. Assessment included the Montgomery Asberg Depression Rating Scale (MADRS), fasting tHcy and the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery.

Results

Individuals with major depression and high tHcy had significantly worse immediate verbal and delayed visual recall. Non-depressed participants with high tHcy had lower MMSE, immediate and delayed recall scores than those with normal tHcy. The odds of cognitive inefficiency for those with high tHcy was nearly doubled for the MMSE (OR 1.9, 95%CI 1.1–3.3), immediate (OR 1.9, 95%CI 1.1–3.5) and delayed (OR 1.9, 95%CI 1.1–3.4) word recall after adjusting for age, gender, IHD and MADRS score.

Limitations

The presence of sub-syndromal depressive symptoms in our non-depressed group and exclusion of participants with established cognitive impairment may limit the generalizability of this study.

Conclusions

Elevated tHcy was associated with weaker performance in tests of immediate and delayed memory and global cognitive performance when compared to those with normal tHcy independent of the presence of major depression or the severity of depressive symptoms. Homocysteine lowering B-vitamin supplementation may offer a potential therapeutic target to try and mitigate the often-disabling impact of cognitive deficits found in this population.     

Comparative analysis of different methods used for molecular characterization of Burkholderia cepacia complex isolated from noncystic fibrosis conditions

PurposeBurkholderia is a Gram-negative opportunistic bacterium capable of causing severe nosocomial infections. The aim of this study was to characterize Burkholderia cepacia complex and to compare different molecular methods used in its characterization.MethodsIn this study, 45 isolates of Burkholderia cepacia complex (Bcc) isolated from clinical cases were subjected to RAPD (Random amplified polymorphic DNA), recA-RFLP (Restriction fragment length polymorphism), 16SrDNA-RFLP, whole-cell protein analysis, recA DNA sequencing and biofilm assay.ResultsOf the 45 isolates tested, 97.7% were sensitive to ceftazidime, 82.2% were sensitive to Cotrimoxazole, 73.3% were sensitive to meropenem, 55.5% were sensitive to minocycline and 42.2% were sensitive to levofloxacin. Majority of the isolates harbored all the tested virulence genes except bpeA and cblA. The RAPD generated 11 groups (R1-R11), recA-RFLP 10 groups (A1-A10), 16SrRNA-RFLP 5 groups (S1–S5) and SDS-PAGE (Sodium Dodecyl Sulphate-Polyacrylamide gel electrophoresis) whole cell protein analysis revealed 12 groups (C1–C12). recA sequencing revealed that most of the isolates belonging to the genomovar III Burkholderia cenocepacia. Though all the methods are found to be efficient in differentiating Burkholderia spp., recA-RFLP was highly discriminatory at 96% similarity value. The study also identified a new strain Burkholderia pseudomultivorans for the first time in the country. Further, recA sequencing could identify the strains to species level. Majority of the multidrug-resistant strains also showed moderate to strong biofilm-forming ability, which further contributes to the virulence characteristics of the pathogens.ConclusionsThe study highlights the importance of combination of molecular methods to characterize Burkholderia cepacia complex. Molecular typing of these human pathogens yields important information for the clinicians in order to initiate the most appropriate therapy in the case of severe infections and to implement preventive measures for the effective control of transmission of Burkholderia spp.     

Aspiration cytology diagnosis of a primary amyloid tumor of thoracic vertebra: a case report

Isolated primary amyloid tumor of bone is rare; however, preoperative diagnosis can be rewarding because the prognosis is excellent. There are no clinical or roentgenographic criteria that can establish this diagnosis. There are few previous reports of fine-needle aspiration (FNA) where diagnosis of amyloidoma was made retrospectively. They describe the presence of extracellular hyaline material along with plasma cells and lymphocytes. A 35-year-old female was referred to the FNA clinic with swelling in the right upper chest wall. Radiologic findings revealed a destructive lytic lesion involving the bodies of D1 and D2 vertebrae with extension into surrounding soft tissue. Repeated FNA smears were hypocellular but had abundant homogeneous flocculent material, which stained positive with Congo red. A few plasma cells and foreign-body giant cells were also seen. We conclude that preoperative FNA cytology diagnosis of amyloid tumor is possible. Hypocellular smears with flocculent material, plasma cells, and foreign-body giant cells in absence of granulation tissue should suggest the diagnosis.     

Imaging left ventricular tissue mechanics and hemodynamics during supine bicycle exercise using a combined tagging and phase‐contrast MRI pulse sequence

Imaging the left ventricular mechanical and hemodynamic response to the stress of exercise may offer early prognosis in select patients with cardiac disease. Here, we demonstrate the feasibility of obtaining simultaneous measurements of longitudinal strain and transvalvular blood velocity during supine bicycle exercise stress in a wide bore magnetic resonance scanner. Combining information from the two datasets, we observe that although the time to peak strain (33.28 ± 1.86 versus 25.7 ± 2.12 as % of R–R interval) and time to peak mitral inflow velocity (44.37 ± 5.21 versus 35.5 ± 4.19 as % of R–R interval) from R‐wave of the QRS complex occurred earlier during stress, the time from peak strain to peak mitral inflow velocity was not statistically different (16.5 ± 3.23 versus 13.4 ± 3.06). Further, the percentage of longitudinal relaxation at peak mitral inflow velocity was higher during stress (63.5 ± 7.72 versus 84.32 ± 6.24). These results suggest that although diastole is shortened, early diastolic filling efficiency is augmented during exercise stress in normal volunteers in an effort to maintain stroke volume. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Dissociative extraction and reconstitution of extracellular matrix components involved in local bone differentiation.

Subcutaneous implantation of demineralized diaphyseal bone matrix in allogeneic rats results in the local induction of endochondral bone differentiation. We have explored the potential of three dissociative extractants, 4 M guanidine hydrochloride (Gdn . HCl), 8 M urea/1 M NaCl, and 1% NaDodSO4 at pH 7.4, containing protease inhibitors to solubilize putative inductive molecules in the bone matrix. Extraction of bone matrix with any one of these extracts resulted in the loss of the bone inductive property. The solubilized extracts were then reconstituted with the residue by dialysis against water. The various reconstituted matrices were bioassayed for bone inductive potential by quantitation of alkaline phosphatase activity and 45Ca incorporation on day 12 after implantation. There was complete recovery of biological activity after reconstitution of the residues with each of the three extracts. Polyacrylamide gel electrophoresis of the extracts revealed similar protein profiles. Gel filtration of the 4 M Gdn. HCl extract on Sepharose CL-4B showed a heterogeneous broad peak. When fractions of that peak containing proteins less than 50,000 daltons were reconstituted with inactive 4 M Gdn . HCl-treated bone matrix and then implanted, new bone was induced. These observations demonstrate the dissociative extraction and successful biological reconstitution of bone inductive macromolecules in demineralized bone matrix.     

Posterior fossa subdural empyema in children��management and outcome

Aims  

The aims of this study were to analyze the clinical features, radiologic findings, bacteriologic spectrum, and management protocols and outcomes in posterior fossa subdural empyemas in children.     

Comparative efficacy and safety of topical permethrin, topical ivermectin, and oral ivermectin in patients of uncomplicated scabies

Background: Ivermectin has opened a new era in the management of scabies as orally effective drug. However, topical route has been little explored for ivermectin. Aims: To compare the efficacy and safety of topical permethrin, oral ivermectin, and topical ivermectin in the treatment of uncomplicated scabies. Methods: This was an open-label, randomized, comparative, parallel clinical trial conducted in 315 patients, randomly allocated to 3 groups. First group received permethrin 5% cream as single application, second group received tablet ivermectin 200 mcg/kg as single dose, and third group received ivermectin 1% lotion as single application. All the patients received anti-histaminic for pruritus. The patients were followed up at intervals of 1, 2, 3, and 4 weeks. If there were no signs of cure, the same intervention was repeated at each follow up. Primary efficacy variable was clinical cure of lesions. Statistical analysis was done by chi square test and one way ANOVA test using SPSS version 12. Results: At the end of first week, cure rate was 74.8% in permethrin group, 30% in oral ivermectin group, and 69.3% in topical ivermectin group (P < 0.05). At the end of second week, cure rate was 99% in permethrin group, 63% in oral ivermectin group, and 100% in topical ivermectin group (P < 0.05). At the end of third week, 100% cure rate was observed in permethrin and topical ivermectin group while 99% in oral ivermectin group (P = 0.367). No serious adverse events were observed. Conclusions: Permethrin and topical ivermectin were equally effective against scabies while oral ivermectin was significantly less effective up to 2 weeks. Topical ivermectin can be used as an alternative to permethrin.     

Dual-labeled trastuzumab-based imaging agent for the detection of human epidermal growth factor receptor 2 overexpression in breast cancer.

Overexpression of the human epidermal growth factor receptor (HER) family has been implicated in cancer because of its participation in signaling pathways regulating cellular proliferation, differentiation, motility, and survival. In this work, we exploited the extracellular binding property of trastuzumab, a clinically therapeutic monoclonal antibody to the second member of the HER family (HER2), to design a diagnostic imaging agent, ((111)In-DTPA)(n)-trastuzumab-(IRDye 800CW)(m), that is dual labeled with (111)In, a gamma-emitter, and a near-infrared (NIR) fluorescent dye, IRDye 800CW, to detect HER2 overexpression in breast cancer cells. The stoichiometric ratios "n" and "m" refer to the number of diethylenetriaminepentaacetic acid dianhydride (DTPA) and IRDye 800CW molecules bound per trastuzumab molecule, respectively. METHODS: Fluorescence microscopy and confocal microscopy were used to determine the molecular specificity of (DTPA)(n)-trastuzumab-(IRDye800)(m) in vitro in SKBr3 (HER2-positive) and MDA-MB-231 (HER2-negative) breast cancer cells. SKBr3 cells were incubated with (DTPA)(n)-trastuzumab-(IRDye800)(m) or IRDye800CW or pretreated with trastuzumab or human IgG followed by (DTPA)(n)-trastuzumab-(IRDye800)(m) and examined under a fluorescence microscope. For in vivo characterization, athymic nude mice bearing HER2-overexpressing SKBr3-luc subcutaneous xenografts were injected intravenously with ((111)In-DTPA)(n)-trastuzumab-(IRDye800)(m) and imaged with SPECT and NIR fluorescence imaging at 48 h. Tumor-bearing mice were also injected intravenously with trastuzumab 24 h before administration of ((111)In-DTPA)(n)-trastuzumab-(IRDye800)(m). Nonspecific uptake in the SKBr3-luc tumors was analyzed by injecting the mice with IRDye 800CW and ((111)In-DTPA)(p)-IgG-(IRDye800)(q), where "p" and "q" are the stoichiometric ratios of DTPA and IRDye 800CW bound per IgG antibody, respectively. RESULTS: (DTPA)(n)-trastuzumab-(IRDye800)(m) showed significantly greater binding to SKBr3 cells than to MDA-MB-231 cells. Confocal imaging revealed that this binding occurred predominantly around the cell membrane. Competitive binding studies with excess trastuzumab before incubation with (DTPA)(n)-trastuzumab-(IRDye800)(m) abolished this binding affinity, but pretreatment with nonspecific IgG did not alter binding. In vivo nuclear and optical imaging of SKBr3-luc xenografts injected with ((111)In-DTPA)(n)-trastuzumab-(IRDye800)(m) revealed significantly more uptake in the tumor region than in the contralateral muscle region. The tumor-to-muscle ratio decreased in mice pretreated with trastuzumab and in mice injected with IRDye 800CW and ((111)In-DTPA)(p)-IgG-(IRDye800)(q). Ex vivo imaging of dissected organs confirmed these results. Finally, coregistration of histologic hematoxylin-eosin stains with autoradiography signals from tumor and muscle tissue slices indicated that ((111)In-DTPA)(n)-trastuzumab-(IRDye800)(m) bound only in tumor tissue and not to muscle. CONCLUSION: Dual-labeled ((111)In-DTPA)(n)-trastuzumab-(IRDye800)(m) may be an effective diagnostic biomarker capable of tracking HER2 overexpression in breast cancer patients.     

The use of CRP within a clinical prediction algorithm for the differentiation of septic arthritis and transient synovitis in children

Clinical prediction algorithms are used to differentiate transient synovitis from septic arthritis. These algorithms typically include the erythrocyte sedimentation rate (ESR), although in clinical practice measurement of the C-reactive protein (CRP) has largely replaced the ESR. We evaluated the use of CRP in a predictive algorithm. The records of 311 children with an effusion of the hip, which was confirmed on ultrasound, were reviewed (mean age 5.3 years (0.2 to 15.1)). Of these, 269 resolved without intervention and without long-term sequelae and were considered to have had transient synovitis. The remaining 42 underwent arthrotomy because of suspicion of septic arthritis. Infection was confirmed in 29 (18 had micro-organisms isolated and 11 had a high synovial fluid white cell count). In the remaining 13 no evidence of infection was found and they were also considered to have had transient synovitis. In total 29 hips were categorised as septic arthritis and 282 as transient synovitis. The temperature, weight-bearing status, peripheral white blood cell count and CRP was reviewed in each patient. A CRP > 20 mg/l was the strongest independent risk factor for septic arthritis (odds ratio 81.9, p < 0.001). A multivariable prediction model revealed that only two determinants (weight-bearing status and CRP > 20 mg/l) were independent in differentiating septic arthritis from transient synovitis. Individuals with neither predictor had a < 1% probability of septic arthritis, but those with both had a 74% probability of septic arthritis. A two-variable algorithm can therefore quantify the risk of septic arthritis, and is an excellent negative predictor.