Accumulation of prion protein in the vagus nerve in creutzfeldt–jakob disease

Disease‐associated proteins are thought to propagate along neuronal processes in neurodegenerative diseases. To detect disease‐associated prion protein (PrP^Sc) in the vagus nerve in different forms and molecular subtypes of Creutzfeldt–Jakob disease (CJD), we applied 3 different anti‐PrP antibodies. We screened the vagus nerve in 162 sporadic and 30 genetic CJD cases. Four of 31 VV‐2 type sporadic CJD and 7 of 30 genetic CJD cases showed vagal PrP^Sc immunodeposits with distinct morphology. Thus, PrP^Sc in CJD affects the vagus nerve analogously to α‐synuclein in Parkinson disease. The morphologically diverse deposition of PrP^Sc in genetic and sporadic CJD argues against uniform mechanisms of propagation of PrP^Sc. Ann Neurol 2019;85:782–787     

The effect of magnesium sulfate on large cerebral artery blood flow in preeclampsia

Objectives.?To determine the effect of a 6 gram intravenous bolus of magnesium sulfate on maternal cerebral blood flow in women with preeclampsia.

Study Desiqn.?Velocity-encoded phase-contrast magnetic resonance imaging studies were performed on twelve preeclamptic women prior to and immediately after infusion of a 6 gram magnesium sulfate loading dose. Cerebral blood flow was determined at the bilateral proximal middle and posterior cerebral arteries. Study participants returned 6 weeks postpartum for a non-pregnant measurement of cerebral blood flow. The Wilcoxon paired-sample test was used with statistical significance defined as p<0.05.

Results.?There was no significant difference in cerebral vessel diameter nor blood flow for any of the examined arteries between the pre- and post magnesium sulfate therapy states.

Conclusions.?The absence of a significant difference in cerebral blood flow of the middle and posterior cerebral arteries before and after infusion of a 6 gram loading dose of magnesium sulfate in women with preeclampsia could suggest the absence of vasoconstriction of the large cerebral arteries in preeclampsia and question the role of magnesium sulfate as a vasodilator of these arteries.     

Comparison of dynamic MR imaging of the breast and sestamibi scintimammography for evaluation of indeterminate mammographic lesions

The aim of this study was to compare Tc-99m sestamibi scintimammography and dynamic contrast-enhanced MR imaging for the evaluation of indeterminate mammographic lesions. Forty patients with questionable mammographic findings were included in a prospective study. Thirty lesions were non-palpable. Mean lesion size was 1.6+/-0.7 cm (range 0.5-3.5 cm). Scintigraphy was considered as malignant when focal tracer accumulation was present. In MR imaging, lesions were classified according to their signal intensity time course: no enhancement or steady enhancement with low signal intensity (M0); steady enhancement with high signal intensity (M1); or rapid enhancement with plateau (M2) or washout (M3). Lesions classified as M2 or M3 were considered as suspicious for malignancy. Histopathologic evaluation was performed in 24 lesions. In 16 cases lesions were classified as benign from follow-up examinations (mean 24 months). Malignancies were proven in 14 patients (9 invasive carcinomas, 5 ductal carcinoma in situ). Sensitivity of MR imaging was 12 of 14 (86%) and sensitivity of scintimammography was 8 of 14 (57%). One of 26 benign lesions was false positive at MR imaging. Scintigraphy showed no false-positive results. In conclusion, magnetic resonance imaging provided high accuracy in evaluation of indeterminate mammographic lesions. Sensitivity of scintimammography was too low in detecting small carcinomas.     

Protheseninfektionen im aortofemoralen Bereich und ihre Vermeidung

Vascular prosthesis infections are potentially severe adverse events following vascular reconstruction. They are often associated with a high morbidity and mortality, especially in the aortofemoral region. The present article outlines the diagnosis, prevention and treatment of vascular graft infections in a clinical setting. The clinical presentation, inflammatory markers, microbiological work-up and imaging studies can contribute to diagnosing a prosthesis infection. Regarding the bacterial spectrum involved in the etiology of prosthesis infections, single organism infections (monoinfections) have become less significant over the past years, whereas infections with multiple organisms now constitute the most abundant microbiological constellation. Also, infections with resistant bacterial strains have been increasing in number over the past years and deserve special consideration. It remains unclear whether both aspects are due to a true epidemiological change or are the result of advanced molecular microbiological diagnostic methods. While during the past decades perioperative antibiotic prophylaxis was regarded as the most important measure for preventing prosthesis infections in vascular surgery, other primary preventive hygiene strategies have been increasingly explored and grouped together in the sense of preventive bundles. In most cases of deep postoperative infections involving a prosthetic device in the aortofemoral region, explantation of the prosthesis will be required. In situ and extra-anatomical reconstructions are often performed in such cases and the decision process to develop an optimal treatment plan must consider several individual factors. In select patients, palliative preservation of the prosthesis despite surrounding infection (i.e. graft salvage) and best conservative management in combination with local surgical measures, such as incision and drainage and vacuum therapy, deserve consideration as a treatment option for patients with a high surgical risk.     

The relevance of team characteristics and team directed strategies in the implementation of nursing innovations: A literature review

BackgroundImplementation of innovations is a complex and intensive procedure in which different strategies can be successful. In nursing, strategies often focus on intrinsic motivation, competencies and attitudes of individual nurses while ignoring the social context. Since nurses often work in teams, identifying relevant team characteristics and successful team directed strategies may contribute to the implementation of innovations. The literature was searched for evidence.MethodsA literature review was performed including key words related to nursing teams, innovations, team characteristics and team-directed strategies. On-line databases were searched (MEDLINE, CINAHL, PsycINFO, ERIC database and Cochrane reviews CENTRAL). The journal Quality and Safety in Healthcare (QSHC) was hand searched. Methodological quality was assessed.ResultsInitially, 323 titles were found. Screening of titles and abstracts and full texts resulted in nine articles meeting the inclusion criteria. The methodological quality of the studies was generally low. The innovations included different types of practices. Fifteen different team characteristics were labeled according to six features of successful teams.Twenty-one different team-directed strategies were identified and inductively categorized.ConclusionFew studies and little evidence were found for the relevance of team characteristics and team directed strategies in the implementation of nursing innovations. Feedback was most frequently used as a strategy. Leadership could be labeled as a team characteristic as well as a team directed strategy. Further research should be of good methodological quality and focusing on patient outcomes and time and costs invested in strategy delivery. This increases scientific knowledge on nursing implementation strategies focusing on leadership.     

Increased plasma levels of the novel vasoconstrictor peptide endothelin in severe pre-eclampsia

Plasma endothelin levels were studied in 29 pregnancies.

Levels were found to be increased in 9 pregnancies complicated by pregnancy-induced hypertensive disease and/or pre-eclampsia as compared to levels in 14 normotensive pregnancies with gestational age varying between 24–40 weeks with normal Doppler flow velocity waveforms of the uterine arcuate arteries, and 6 normotensive pregnancies with abnormal Doppler flow velocity waveforms at 24 weeks' gestation.

Two patients with severe pre-eclampsia showed a rise in plasma endothelin levels, suggesting a correlation between plasma endothelin levels and the disease process. Endothelin is produced by endothelial cells of blood vessels; it is the most potent vasoconstrictor known to date. For this reason it has been suggested that endothelin might be important in the control of systemic blood pressure and local blood flow, both disturbed in pre-eclampsia. The conclusion of this study is that the venous plasma level of endothelin would seem to be a marker for severe disease, however, without any predictive value.     

Mapping of rat brain using the Synuclein-1 monoclonal antibody reveals somatodendritic expression of alpha-synuclein in populations of neurons homologous to those vulnerable to Lewy body formation in human synucleopathies

The neuronal protein alpha-synuclein has been implicated in the pathogenesis of Parkinson disease and other neurodegenerative diseases. Although many studies report that alpha-synuclein expression is restricted to neuronal presynaptic terminals, this protein aggregates in Lewy bodies in somata that are typically distant from their axon terminals. Few studies have addressed this paradox and there has been no compelling explanation proposed for the apparent discrepancy between the locus of neuronal alpha-synuclein expression and the loci of Lewy bodies in the majority of Parkinson disease cases. We explored this issue by extensively characterizing the monoclonal antibody Synuclein-1 (Syn-1) and using this highly selective antibody to map the distribution of alpha-synuclein throughout rat brain and in human substantia nigra (SN). Additionally, alpha-synuclein expression in rat SN detected by 2 polyclonal antibodies against alpha-synuclein was compared with that detected by the Syn-1 antibody. In contrast with many previous reports, alpha-synuclein was detected by Syn-1 in neuronal somata and dendrites in restricted brain regions, as well as more ubiquitously in axons and terminals. The strongest alpha-synuclein neuronal expression in rat was found in brainstem and cortical regions that are homologous to regions prone to Lewy body formation in humans. The Syn-1 antibody labeled abundant somatodendritic alpha-synuclein in both rat and human SN, a major locus of Lewy body formation and neurodegeneration in Parkinson disease. By contrast, very few immunoreactive somata in the rat SN were labeled by the 2 polyclonal antibodies. We explore possible explanations for the differences in conflicting reports of patterns of alpha-synuclein expression in brain, including differences among antibodies.     

CD154 is expressed during treatment with calcineurin inhibitors after organ transplantation

BACKGROUND: CD154 (CD40 ligand) monoclonal antibody prevents allograft rejection in rodents and monkeys. Inasmuch as calcineurin inhibitors (CI) inhibit CD154 expression by pharmacologic agents in vitro, we investigated whether CD154 is also inhibited by CI in vivo and in vitro during allogeneic stimulation. METHODS: CD154 expression was determined by immunohistochemistry and flow cytometry in human lymph nodes and spleen sections from rhesus monkeys with or without CI treatment. The effect of CI on induction of CD154 expression was studied by stimulating lymphocytes with phorbol 12-myristate 13-acetate (PMA) and ionomycin or with allogeneic monocyte-derived mature dendritic cells. RESULTS: Lymph nodes from patients with or without CI cyclosporine (CsA) or FK506 (FK) treatment showed comparable CD154 expression, which was present on the cell surface of T cells. CD154-expressing cells were also present in spleens from monkeys treated with CsA in comparable numbers to those in the nontreated group. Moreover, in several liver transplant rejection biopsies taken during CI therapy CD154-expressing cells were observed. In vitro, CsA and FK strongly inhibited induction of CD154 expression on peripheral blood mononuclear cells by pharmacologic stimuli. Maximum inhibition was found at 50 ng/ml CsA and 20 ng/ml FK. CD154 expression induced by dendritic cells in peripheral blood mononuclear cells or spleen cells was also almost completely inhibited by CsA. CONCLUSION: Although CI strongly suppressed pharmacologic and allogeneic induction of CD154 expression on T cells in vitro at concentrations at approximately clinical trough levels, CD154 is prominently expressed during CI therapy in lymphoid tissue and (sporadically) in liver allografts. This suggests that the CD154-CD40 pathway remains functional during CI therapy, which may contribute to allograft rejections in the clinical setting.     

MR imaging of the brain in pediatric patients: diagnostic value of HASTE sequences

OBJECTIVE: The objective of this study was to determine the diagnostic value of half-Fourier single-shot turbo spin-echo (HASTE) sequences in MR imaging of the brain in pediatric patients. SUBJECTS AND METHODS: HASTE sequences were performed in 80 infants and children. Two radiologists who were unaware of the patients' medical histories independently reviewed the images for the presence of nine findings: defects of the parenchyma, hypoplasia or agenesis of the corpus callosum, edema, signs of increased intracranial pressure, myelination disorders, migration disorders, malformations, tumors, and widening of spaces of the cerebrospinal fluid. A conventional MR imaging examination that served as the reference examination was evaluated by the same two radiologists in a final consensus interpretation. The findings detected on the HASTE images were compared with the findings seen on the conventional MR images. The sensitivity and specificity of HASTE sequences were calculated, and Cohen's kappa statistic was used to determine interobserver agreement. RESULTS: Both radiologists correctly diagnosed all 20 defects of the parenchyma that were present in the patients. Radiologist 1 correctly identified 20 and radiologist 2 correctly identified 21 of the 22 patients with hypoplasia or agenesis of the corpus callosum. Both radiologists correctly diagnosed edema in eight of the nine patients in whom edema was present, and both correctly identified signs of increased intracranial pressure in eight of the nine children who had this condition. Radiologist 1 correctly diagnosed seven and radiologist 2 correctly identified nine of the 11 cases of myelination disorders. Both radiologists correctly diagnosed six of the 14 cases with migration disorders. All 13 brain malformations present in the patients were correctly identified by both reviewers. Both radiologists correctly identified all 11 patients with tumors, and both correctly identified all 35 patients with widening of spaces of the cerebrospinal fluid. CONCLUSION: HASTE images are highly sensitive for excluding the presence of brain tumor, hydrocephalus, or malformations of the brain. HASTE images are not reliable for evaluating patients with suspected myelination disorders or migration disorders.