A qualitative test of the balloon model for BOLD-based MR signal changes at 3T.

The aim of this study was to adapt the balloon model for BOLD-based MR signal changes to a magnetic field strength of 3T and to examine its validity. The simultaneous measurement of BOLD and diffusion-weighted BOLD responses was performed. The amplitude of the BOLD peak was found to be similar for all subjects when a short visual stimulus of 6 sec was used. The rise-time to the BOLD peak and the shape and depth of the poststimulus undershoot varied significantly. A fit of the experimental BOLD responses was found to be possible by use of parameters within a reasonable physiological range. The relations between these parameters and their influence on the modeled BOLD responses is discussed. A prediction of the balloon model is the occurrence of a BOLD overshoot, i.e., a lag between the changes of the blood volume and the blood flow after the start of the stimulation. Experimental evidence for the existence of a BOLD overshoot is presented.     

Hepatic perfusion index and the evolution of liver metastases

A total of 150 patients with primary carcinoma of the gastrointestinal tract had first-pass technetium colloid scintigraphy to estimate the hepatic perfusion index (HPI). Postoperative follow-up over 2-4 years shows that the HPI remains a sensitive method of detecting hepatic metastases, even in patients whose liver appeared normal at laparotomy. HPI was elevated in 94% of patients with liver metastases found at laparotomy; 87% of patients with occult metastases which became overt within 3 years of surgery had elevated HPI; and 91% of all patients who have to date developed hepatic metastases had elevated HPI at presentation. Of all patients with elevated HPI, 82% had metastases which were either apparent at surgery or became detectable by other means within 3 years.     

Cardiac arrhythmias in the critically ill

Arrhythmias are a common problem in the critically ill and they can have significant effects on patient outcome. They often require immediate and swift action and it is, therefore, essential that clinicians have a structured approach to the recognition and management of arrhythmias. Here, we provide a framework for the appropriate management of the more frequently encountered cardiac arrhythmias in critical care. We include the algorithms from the 2015 Resuscitation Council Guidelines for reference.     

Detection of Hepatitis B Virus DNA Sequences in Liver in HBsAg Seronegative Patients with Liver Disease with and without Anti-HBc Antibodies

Excluding studies from Brechot and co-workers, little supporthas been found for a role of the hepatitis B virus in the pathogenesisof HBsAg seronegative patients with predominantly chronic liverdiseases, including primary liver cancer. In this study liverDNA from 59 predominantly British patients (four cases withpaired biopsies, 6–12 months apart) with different, mostlychronic, liver diseases was analysed by molecular hybridization.All were seronegative for HBsAg and serum hepatitis B virusDNA (dot blot hybridization) and their liver diseases were believedto be unrelated to hepatitis B virus infection. Hepatitis Bvirus DNA was detected in liver of 11 (18.6 per cent) patients;nine had episomal(3.2 Kb) DNA and eight had higher molecularweight bands suggesting integrated forms. Six patients werealso seronegative for anti-HBc. Patients of UK and non-UK originwere equally represented. Hepatitis B virus DNA was detectedin serum of six of nine patients tested using the polymerasechain reaction. The detection of hepatitis B virus DNA in liverand in serum by this assay in a significant proportion of patientswith chronic liver disease, hitherto unsuspected of being hepatitisB virus-related, suggests a possible role for this virus inlow- as well as high-prevalence countries.     

Activation of Rabbit Hageman Factor by Homogenates of Cultured Rabbit Endothelial Cells

Rabbit Hageman factor was proteolytically cleaved and activated by a homogenate prepared from cultured rabbit endothelial cells. Cleavage of radiolabeled Hageman factor was monitored by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Endothelial cell-mediated cleavage of Hageman factor was demonstrated both in a purified system and in plasma, was time and concentration dependent, and was associated with formation of the characteristic 28,000 M(r) form of active Hageman factor. The rate of cleavage of Hageman factor was not affected by Triton X-100 (Rohm and Haas, Co., Philadelphia, Pa.), hexadimethrine bromide (Polybrene, Aldrich Chemical Co., Inc., Milwaukee, Wis.), hirudin, soybean trypsin inhibitor, or antisera to plasminogen or prekallikrein. However, cleavage was enhanced by kaolin, and was inhibited by diisopropyl-fluorophosphate. The enzyme responsible for cleavage of Hageman factor was localized to the 100,000-g-sedimentable, subcellular fraction of the endothelial cell homogenate and was relatively specific, because neither radiolabeled rabbit Factor XI nor rabbit prekallikrein were themselves proteolytically cleaved by the endothelial cell homogenate. However, when these molecules were incubated with the homogenate in the presence of Hageman factor, both Factor XI and prekallikrein were cleaved, demonstrating that Hageman factor had been activated by the endothelial cell homogenate. Furthermore, the kallikrein generated by endothelial cell homogenate-activated Hageman factor was capable of liberating kinin from high molecular weight kininogen as measured by bioassay. Cultured rabbit endothelial cells, therefore, possess the capacity to activate Hageman factor by proteolysis. This may be one mechanism for Hageman factor activation in vivo.     

Use of Short Intertrial Intervals in Single-Trial Experiments: A 3T fMRI-Study

We investigated the detectability of task-related changes in the fMRI-signal in an averaged single trial design under systematic variation of intertrial intervals (ITI) in the range between 4 and 12 s. Investigation of the signal timecourses showed a shortening of the baseline period and subsequently a reduction in signal amplitude with decreasing ITI. The main finding is that effect size, i.e., the ratio of task-related signal changes and error variance remained approximately constant from ITI of 12 s down to 6 s. At ITI = 4 s, the effect size was reduced by about 50%. The effects of ITI reduction were comparable in all six cortical ROI which were analyzed. In two subcortical ROI, effect size was already reduced at longer ITI. At ITI = 4 s, the rising flank of the BOLD response was delayed compared to longer ITI. When the data were corrected for the temporal overlap of successive BOLD-responses, the signal amplitudes at ITI = 4 s were comparable to the amplitudes measured at an interval of 12 s. This indicated that the amplitude reduction was mainly due to a linear superposition of the contiguous BOLD-responses.     

Variation in 24 hemostatic genes and associations with non-fatal myocardial infarction and ischemic stroke.

BACKGROUND: Arterial thrombosis involves platelet aggregation and clot formation, yet little is known about the contribution of genetic variation in fibrin-based hemostatic factors to arterial clotting risk. We hypothesized that common variation in 24 coagulation-fibrinolysis genes would contribute to risk of incident myocardial infarction (MI) or ischemic stroke (IS). METHODS: We conducted a population-based, case-control study. Subjects were hypertensive adults and postmenopausal women 30-79 years of age, who sustained a first MI (n = 856) or IS (n = 368) between 1995 and 2002, and controls matched on age, hypertension status, and calendar year (n = 2,689). We investigated the risk of MI and IS associated with (i) global variation within each gene as measured by common haplotypes and (ii) individual haplotypes and single nucleotide polymorphisms (SNPs). Significance was assessed using a 0.2 threshold of the false discovery rate q-value, which accounts for multiple testing. RESULTS: After accounting for multiple testing, global genetic variation in factor (F) VIII was associated with IS risk. Two haplotypes in FVIII and one in FXIIIa1 were significantly associated with increased IS risk (all q-values < 0.2). A plasminogen gene SNP was associated with MI risk. All are new discoveries not previously reported. Another 24 tests had P-values < 0.05 and q-values > 0.2 in MI and IS analyses, 23 of which are new and hypothesis generating. CONCLUSIONS: Apart from the association of FVIII variation with IS, we found little evidence that common variation in the 24 candidate fibrin-based hemostasis genes strongly influences arterial thrombotic risk, but our results cannot rule out small effects.