Quantitative Evaluation of Scintillation Camera Imaging Characteristics of Isotopes Used in Liver Radioembolization

Scintillation camera imaging is used for treatment planning and post-treatment dosimetry in liver radioembolization (RE). In yttrium-90 (90Y) RE, scintigraphic images of technetium-99m (99mTc) are used for treatment planning, while 90Y Bremsstrahlung images are used for post-treatment dosimetry. In holmium-166 (166Ho) RE, scintigraphic images of 166Ho can be used for both treatment planning and post-treatment dosimetry. The aim of this study is to quantitatively evaluate and compare the imaging characteristics of these three isotopes, in order that imaging protocols can be optimized and RE studies with varying isotopes can be compared.Phantom experiments were performed in line with NEMA guidelines to assess the spatial resolution, sensitivity, count rate linearity, and contrast recovery of 99mTc, 90Y and 166Ho. In addition, Monte Carlo simulations were performed to obtain detailed information about the history of detected photons. The results showed that the use of a broad energy window and the high-energy collimator gave optimal combination of sensitivity, spatial resolution, and primary photon fraction for 90Y Bremsstrahlung imaging, although differences with the medium-energy collimator were small. For 166Ho, the high-energy collimator also slightly outperformed the medium-energy collimator. In comparison with 99mTc, the image quality of both 90Y and 166Ho is degraded by a lower spatial resolution, a lower sensitivity, and larger scatter and collimator penetration fractions.The quantitative evaluation of the scintillation camera characteristics presented in this study helps to optimize acquisition parameters and supports future analysis of clinical comparisons between RE studies

Heat Shock Proteins and Amateur Chaperones in Amyloid-Beta Accumulation and Clearance in Alzheimer’s Disease

The pathologic lesions of Alzheimer’s disease (AD) are characterized by accumulation of protein aggregates consisting of intracellular or extracellular misfolded proteins. The amyloid-β (Aβ) protein accumulates extracellularly in senile plaques and cerebral amyloid angiopathy, whereas the hyperphosphorylated tau protein accumulates intracellularly as neurofibrillary tangles. “Professional chaperones”, such as the heat shock protein family, have a function in the prevention of protein misfolding and subsequent aggregation. “Amateur” chaperones, such as apolipoproteins and heparan sulfate proteoglycans, bind amyloidogenic proteins and may affect their aggregation process. Professional and amateur chaperones not only colocalize with the pathological lesions of AD, but may also be involved in conformational changes of Aβ, and in the clearance of Aβ from the brain via phagocytosis or active transport across the blood–brain barrier. Thus, both professional and amateur chaperones may be involved in the aggregation, accumulation, persistence, and clearance of Aβ and tau and in other Aβ-associated reactions such as inflammation associated with AD lesions, and may, therefore, serve as potential targets for therapeutic intervention

Specific detection of fungal pathogens by 18S rRNA gene PCR in microbial keratitis

<p>Abstract</p> <p>Background</p> <p>The sensitivity and specificity of 18S rRNA polymerase chain reaction (PCR) in the detection of fungal aetiology of microbial keratitis was determined in thirty patients with clinical diagnosis of microbial keratitis.</p> <p>Methods</p> <p>Corneal scrapings from patients were used for Gram stain, culture and PCR analysis. PCR was performed with primer pairs targeted to the 18S rRNA gene. The result of the PCR was compared with conventional culture and Gram staining method. The PCR positive samples were identified by DNA sequencing of the internal transcribed spacer (ITS) region of the rRNA gene. Main outcome measures were sensitivity and specificity of PCR in the detection of fungus in corneal keratitis.</p> <p>Results</p> <p>Combination of microscopy and culture gave a positive result in 11 of 30 samples of microbial keratitis. PCR detected 10 of 11 samples that were positive by conventional method. One of the 19 samples that was negative by conventional method was positive by PCR. Statistical analysis revealed that the PCR to have a sensitivity of 90.9% and specificity of 94.7% in the detection of a fungal aetiology in microbial keratitis.</p> <p>Conclusion</p> <p>PCR is a rapid, sensitive and useful method to detect fungal aetiology in microbial keratitis.</p

Sharp upturn of life expectancy in the Netherlands: effect of more health care for the elderly?

During the 1980s and 1990s life expectancy at birth has risen only slowly in the Netherlands. In 2002, however, the rise in life expectancy suddenly accelerated. We studied the possible causes of this remarkable development. Mortality data by age, gender and cause of death were analyzed using life table methods and age-period-cohort modeling. Trends in determinants of mortality (including health care delivery) were compared with trends in mortality. Two-thirds of the increase in life expectancy at birth since 2002 were due to declines in mortality among those aged 65 and over. Declines in mortality reflected a period rather than a cohort effect, and were seen for a wide range of causes of death. Favorable changes in mortality determinants coinciding with the acceleration of mortality decline were mainly seen within the health care system. Health care expenditure rose rapidly after 2001, and was accompanied by a sharp rise of specialist visits, drug prescriptions, hospital admissions and surgical procedures among the elderly. A decline of deaths following non-treatment decisions suggests a change towards more active treatment of elderly patients. Our findings are consistent with the idea that the sharp upturn of life expectancy in the Netherlands was at least partly due to a sharp increase in health care for the elderly, and has been facilitated by a relaxation of budgetary constraints in the health care system

An Important Role for Syndecan-1 in Herpes Simplex Virus Type-1 Induced Cell-to-Cell Fusion and Virus Spread

Herpes simplex virus type-1 (HSV-1) is a common human pathogen that relies heavily on cell-to-cell spread for establishing a lifelong latent infection. Molecular aspects of HSV-1 entry into host cells have been well studied; however, the molecular details of the spread of the virus from cell-to-cell remain poorly understood. In the past, the role of heparan sulfate proteoglycans (HSPG) during HSV-1 infection has focused solely on the role of HS chains as an attachment receptor for the virus, while the core protein has been assumed to perform a passive role of only carrying the HS chains. Likewise, very little is known about the involvement of any specific HSPGs in HSV-1 lifecycle. Here we demonstrate that a HSPG, syndecan-1, plays an important role in HSV-1 induced membrane fusion and cell-to-cell spread. Interestingly, the functions of syndecan-1 in fusion and spread are independent of the presence of HS on the core protein. Using a mutant CHO-K1 cell line that lacks all glycosaminoglycans (GAGs) on its surface (CHO-745) we demonstrate that the core protein of syndecan-1 possesses the ability to modulate membrane fusion and viral spread. Altogether, we identify a new role for syndecan-1 in HSV-1 pathogenesis and demonstrate HS-independent functions of its core protein in viral spread

Amyloid Oligomer Conformation in a Group of Natively Folded Proteins

Recent in vitro and in vivo studies suggest that destabilized proteins with defective folding induce aggregation and toxicity in protein-misfolding diseases. One such unstable protein state is called amyloid oligomer, a precursor of fully aggregated forms of amyloid. Detection of various amyloid oligomers with A11, an anti-amyloid oligomer conformation-specific antibody, revealed that the amyloid oligomer represents a generic conformation and suggested that toxic β-aggregation processes possess a common mechanism. By using A11 antibody as a probe in combination with mass spectrometric analysis, we identified GroEL in bacterial lysates as a protein that may potentially have an amyloid oligomer conformation. Surprisingly, A11 reacted not only with purified GroEL but also with several purified heat shock proteins, including human Hsp27, 40, 70, 90; yeast Hsp104; and bovine Hsc70. The native folds of A11-reactive proteins in purified samples were characterized by their anti-β-aggregation activity in terms of both functionality and in contrast to the β-aggregation promoting activity of misfolded pathogenic amyloid oligomers. The conformation-dependent binding of A11 with natively folded Hsp27 was supported by the concurrent loss of A11 reactivity and anti-β-aggregation activity of heat-treated Hsp27 samples. Moreover, we observed consistent anti-β-aggregation activity not only by chaperones containing an amyloid oligomer conformation but also by several A11-immunoreactive non-chaperone proteins. From these results, we suggest that the amyloid oligomer conformation is present in a group of natively folded proteins. The inhibitory effects of A11 antibody on both GroEL/ES-assisted luciferase refolding and Hsp70-mediated decelerated nucleation of Aβ aggregation suggested that the A11-binding sites on these chaperones might be functionally important. Finally, we employed a computational approach to uncover possible A11-binding sites on these targets. Since the β-sheet edge was a common structural motif having the most similar physicochemical properties in the A11-reactive proteins we analyzed, we propose that the β-sheet edge in some natively folded amyloid oligomers is designed positively to prevent β aggregation

Simplified automatic method for measuring the visual field using the perimeter ZERK 1

Background: Currently available perimeters have limited capabilities of performing measurements of the visual field in children. In addition, they do not allow for fully automatic measurement even in adults. The patient in each case (in any type of perimeter) has at his disposal a button which he uses to indicate that he has seen a light stimulus. Such restrictions have been offset in the presented new perimeter ZERK 1. Methods: The paper describes a new type of automated, computerized perimeter designed to test the visual field in children and adults. The new perimeter and proprietary software enable to carry out tests automatically (without the need to press any button). The presented full version of the perimeter has been tested on a head phantom. The next steps will involve clinical trials and a comparison with measurements obtained using other types of perimeters. Results: The perimeter ZERK 1 enables automatic measurement of the visual field in two axes (with a span of 870 mm and a depth of 525 mm) with an accuracy of not less than 1o (95 LEDs on each arm) at a typical position of the patient's head. The measurement can be carried out in two modes: default/typical (lasting about 1 min), and accurate (lasting about 10 min). Compared with available and known types of perimeters, it has an open canopy, proprietary software and cameras tracking the eye movement, automatic control of fixation points, light stimuli with automatically preset light stimulus intensity in the following ranges: 550-700 mcd (red 620-630 nm), 1100-1400 mcd (green 515-530 nm), 200-400 mcd (blue 465-475 nm). Conclusions: The paper presents a new approach to the construction of perimeters based on automatic tracking of the eye movements in response to stimuli. The unique construction of the perimeter and the software allow for its mobile use in the examination of children and bedridden patients