Reduced oligomeric and vascular amyloid-β following immunization of TgCRND8 mice with an Alzheimer's DNA vaccine

Immunization with amyloid-β (Aβ) peptide reduces amyloid load in animal studies and in humans; however clinical trials resulted in the development of a pro-inflammatory cellular response to Aβ. Apoptosis has been employed to stimulate humoral and Th2-biased cellular immune responses. Thus, we sought to investigate whether immunization using a DNA vaccine encoding Aβ in conjunction with an attenuated caspase generates therapeutically effective antibodies. Plasmids encoding Aβ and an attenuated caspase were less effective in reducing amyloid pathology than those encoding Aβ alone. Moreover, use of Aβ with an Arctic mutation (E22G) as an immunogen was less effective than wild-type Aβ in terms of improvements in pathology. Low levels of IgG and IgM were generated in response to immunization with a plasmid encoding wild-type Aβ. These antibodies decreased plaque load by as much as 36 ± 8% and insoluble Aβ42 levels by 56 ± 3%. Clearance of Aβ was most effective when antibodies were directed against N-terminal epitopes of Aβ. Moreover, immunization reduced CAA by as much as 69 ± 12% in TgCRND8 mice. Finally, high-molecular-weight oligomers and Aβ trimers were significantly reduced with immunization. Thus, immunization with a plasmid encoding Aβ alone drives an attenuated immune response that is sufficient to clear amyloid pathology in a mouse model of Alzheimer's disease.     

Assessing ethical problem solving by reasoning rather than decision making

Context The assessment of ethical problem solving in medicine has been controversial and challenging. The purposes of this study were: (i) to create a new instrument to measure doctors’ decisions on and reasoning approach towards resolving ethical problems; (ii) to evaluate the scores generated by the new instrument for their reliability and validity, and (iii) to compare doctors’ ethical reasoning abilities between countries and among medical students, residents and experts. Methods This study used 15 clinical vignettes and the think‐aloud method to identify the processes and components involved in ethical problem solving. Subjects included volunteer ethics experts, postgraduate Year 2 residents and pre‐clerkship medical students. The interview data were coded using the instruments of the decision score and Ethical Reasoning Inventory (ERI). The ERI assessed the quality of ethical reasoning for a particular case (Part I) and for an individual globally across all the vignettes (Part II). Results There were 17 Canadian and 32 Taiwanese subjects. Based on the Canadian standard, the decision scores between Taiwanese and Canadian subjects differed significantly, but made no discrimination among the three levels of expertise. Scores on the ERI Parts I and II, which reflect doctors’ reasoning quality, differed between countries and among different levels of expertise in Taiwan, providing evidence of construct validity. In addition, experts had a greater organised knowledge structure and considered more relevant variables in the process of arriving at ethical decisions than did residents or students. The reliability of ERI scores was 0.70–0.99 on Part I and 0.75–0.80 on Part II. Conclusions Expertise in solving ethical problems could not be differentiated by the decisions made, but could be differentiated according to the reasoning used to make those decisions. The difference between Taiwanese and Canadian experts suggests that cultural considerations come into play in the decisions that are made in the course of providing humane care to patients.     

Inadequate dietary calcium and vitamin D intakes in renal-transplant recipients in Ireland.

OBJECTIVE: To quantify the dietary calcium and vitamin D intake in adult renal-transplant recipients attending at a large teaching hospital in Ireland for follow-up. SETTING: Outpatient renal-transplant follow-up clinic. SUBJECTS: Fifty-nine adult renal transplant recipients (58% male) with a mean age of 46 years, a median transplant duration of 6 years, and a mean estimated glomerular filtration rate (eGFR) of 50 mL/min per 1.73 m2. Fifty-three percent were at National Kidney Foundation stage 3 chronic kidney disease, and 14% had stage 4 chronic kidney disease. INTERVENTION: This cross-sectional, observational study used a tailored food frequency questionnaire specific for calcium and vitamin D intake in Irish adults, which was completed during a face-to-face interview with each subject. MAIN OUTCOME MEASURE: The main outcome measure was the average daily dietary and supplemented calcium and vitamin D intake. RESULTS: The median interquartile range (IQR) dietary calcium intake was 820 mg/day (range, 576-1,177 mg/day), and was similar in men and women (recommended intake > or = 1,000 mg/day in adult men and nonmenopausal adult women, > or = 1,500 mg/day in menopausal women). Five participants received calcium supplementation. Overall, 59% of men and 64% of women had total calcium intakes below the recommended amounts. The median IQR estimated dietary vitamin D intake was 5.2 microg/day (range, 2.4-6.4 microg/day) in women, and 4.6 microg/day (range, 2.2-6.6 microg/day) in men (recommended intake, > or = 10 microg/day). Six subjects received vitamin D supplementation. Total vitamin D intakes were suboptimal in 91% of men and 87% of women. Dietary calcium and vitamin D intakes significantly correlated with each other, but neither was significantly related to eGFR category, and was similarly low in both presumed menopausal women and in the initial year posttransplantation. CONCLUSION: These findings suggest that dietary and total calcium and vitamin D intakes in adult renal-transplant patients are in many cases inadequate.     

Cardiac imaging in the evaluation of patients presenting to the emergency department with chest pain

Conclusions  Despite the utility and benefits that each imaging modality has to offer, it is easy to see why there is still no perfect choice for a noninvasive cardiac imaging modality to assist in the management of chest pain patients. All of the current imaging techniques have their own significant strengths and weaknesses when compared with other modalities. SPECT and echocardiography are wellestablished technologies that can directly assess the presence of myocardial ischemia and its functional consequence on RF; newer and more expensive techniques such as MDCT and CMR can directly assess coronary anatomy and have just started to be evaluated in the acute chest pain setting. There are no studies that directly compare these technologies, and more data are clearly needed before the question of whether anatomic imaging versus perfusion/function imaging is the better approach can be answered. Other comparisons such as relative safety, availability, logistics, and cost-effectiveness between the various technologies are also lacking. Of all of the imaging modalities discussed, MCE is the only portable technology. The images do not require expensive software or other technology for offline processing before interpretation, and any trained cardiologist can read the study at the bedside or, potentially, over the Internet, providing near-instantaneous results in the acute cardiac setting, where time is of the essence. MCE is also relatively cheap compared with other technologies, a potential advantage for payors but not necessarily for payees. How reimbursement rates and fee structures eventually affect clinical practice is also unknown. Despite these and other questions that need to be answered before any one technique will be used exclusively, the future of noninvasive cardiac imaging remains an exciting and ever-changing field. The adaptation of any one of these techniques into its proper role in the ED Journal of Nuclear Cardiology Wyrick and Wei 753 Volume 13, Number 6;749-55 Cardiac imaging in patients with chest pain will take considerably more time and effort in terms of research, money, and time-tested clinical experience.     

Five Percent Lidocaine Cream Applied Simultaneously to the Skin and Mucosa of the Lips Creates Excellent Anesthesia for Filler Injections

Background. Injection of filler substances into the lips is painful, and many patients also find the injection of local or regional anesthesia into the lips painful.
Objective. To develop a highly effective and painless form of anesthesia to facilitate injection of filler substances into the lips.
Methods. Five percent lidocaine cream was applied simultaneously to the skin, vermilion, and mucosa of the lips (with the use of a barrier to keep the cream in contact with the mucosa and out of the rest of the mouth) for 20 to 30 minutes.
Results. Profound anesthesia of the lips was reliably produced, with no complications.
Conclusions. This "anesthetic cream block" is easier to perform and better tolerated than injectable anesthetics. Use of this technique is likely to expand the range of physicians who perform filler injections on the lips and will probably also expand the range of patients who wish to have filler injections done on their lips and who (because they had little or no discomfort) are willing to return for additional filler injections in the future.     

Use of a violence risk assessment tool in an acute care hospital: effectiveness in identifying violent patients.

This study examined the use and effectiveness of the Alert assessment form. The form is part of the Alert system, used by one large acute care hospital to identify patients with a propensity for violence. All reported incidents of patient violence from August 1, 2003, through December 31, 2004, were included in patient charts. One hundred seventeen violent patient charts were reviewed and compared with 161 non-violent patient charts, randomly chosen from the same time period. Overall use of the Alert assessment form for violent and non-violent patients was 75.7% and 35.4%, respectively. The assessment form was found to have moderate sensitivity (71%) and high specificity (94%). It is reasonably effective in identifying potentially violent or aggressive patients when it is used according to protocol. Efforts to improve the tool are warranted, as is evaluation of its benefit in settings with low prevalence of violence. Also, greater effort must be taken to prevent violence once an aggressive patient has been identified.     

C2H2-171 : A novel human cDNA representing a developmentally regulated poz domain/zinc finger protein preferentially expressed in brain

We describe a novel human zinc finger cNDA, C2H2-171. This cDNA represents an mRNA which encodes a protein of 484 amino acids and a calculated molecular weight of 54 kD. Four zinc finger-like domains are found in the C-terminal end of the protein. At the N-terminus, C2H2-171 contains a POZ/tramtrack-like domain similar to that found in the tumor associated zinc finger proteins LAZ-3/BCL-6 and PLZ-F, as well as in non-zinc finger proteins. C2H2-171 RNA is preferentially expressed in the brain, and increases during the course of murine development, with maximal expression in the adult. C2H2-171 RNA is differentially expressed in brain regions, with the highest level of expression in the cerebellum. C2H2-171 RNA was expressed at high levels in primary cerebellar granule cell neurons compared to astrocytes. The gene encoding C2H2-171 is highly conserved in vertebrates, and maps to the terminus of human chromosome 1 (1q44-ter). This chromosomal location is associated with a number of cytogenetic aberrations including those involving brain developmental anomalies and tumorigenesis. These data suggest that C2H2-171 may play an important role in vertebrate brain development and function.     

Interpretation of noninvasive oxygen and carbon dioxide data

Canadian Journal of Anesthesia/Journal canadien d'anesthésie -     

Interpreting cerebrospinal fluid pleocytosis in HIV in the era of potent antiretroviral therapy

Background  

Cerebrospinal fluid (CSF) pleocytosis may be seen in asymptomatic HIV-infected individuals. This finding complicates interpretation of CSF abnormalities when such individuals are evaluated for other central nervous system infections. The goal of this study was to determine the relationship between CSF pleocytosis, central nervous system (CNS) antiretroviral penetration, adherence to antiretroviral medication regimens, neurological symptoms and performance on neuropsychological tests.