Use of two parallel oxygenators in a very large patient (2.76 m2) for an acute "A" dissecting aortic aneurysm repair

The very large patient (weight 142 kg, height 197 cm, body surface 2.76 m2) was referred to acute operation with dissecting type A ascending aortic aneurysm. The calculated blood flow was 6.63 l/min. To anticipate potential difficulties with perfusion and oxygenation two oxygenators connected in parallel were incorporated into the circuit. Bentall procedure with ACB to the RCA was performed. The perfusion was uneventful. Bypass time was 259 minutes, cross clamp time 141 minutes, circulatory arrest 7 minutes. The highest oxygenators gas flow was 2.6 l/min with maximum FiO2 0.42. The use of two in parallel connected oxygenators is a very effective, easy and safe method in such extreme perfusions, offering to the perfusionist a great reserve of oxygenator output.     

Human leukocyte antigen DR15 is associated with reduced relapse rate and improved survival after human leukocyte antigen-identical sibling hematopoietic stem cell transplantation.

Human leukocyte antigen (HLA) DR15 is associated with autoimmune cytopenia in patients with aplastic anemia, myelodysplastic syndrome, and paroxysmal nocturnal hemoglobinuria. Presence of this antigen also predicts response to immunosuppressive treatment. If DR15 expression on hematopoietic cells also favors induction of immune responses in an allogeneic setting, a lower relapse rate after hematopoietic stem cell transplantation (HSCT) might result through an enhanced graft-versus-leukemia effect. We retrospectively analyzed outcome of HLA-identical sibling HSCT in 192 consecutive patients with acute or chronic leukemia or non-Hodgkin lymphoma. Patients carrying the DR15 antigen had a higher estimated 5-year overall survival (76%) than did DR15-negative patients (55%; P = .04). Improved survival for DR15 patients was due to a significant decrease in death from relapse (5% for DR15(+) versus 24% for DR15(-); P = .02), whereas no difference was seen for rates of transplant-related mortality (19% and 21%, respectively; P = .76). Findings were confirmed by multivariate analyses. Our results show an association of DR15 with a decreased risk of disease relapse and improved survival after HSCT for leukemia or non-Hodgkin lymphoma. This adds to the growing list of links between DR15 and immune reactions in hematopoiesis.     

Dependence of adaptation of the human vertical angular vestibulo-ocular reflex on gravity

We determined the spatial dependence of adaptive gain changes of the vertical angular vestibulo-ocular reflex (aVOR) on gravity in five human subjects. The gain was decreased for 1 h by sinusoidal oscillation in pitch about a spatial vertical axis in a subject-stationary surround with the head oriented left-side down. Gains were tested by sinusoidal oscillation about a spatial vertical axis while subjects were tilted in 15° increments from left- to right-side down positions through the upright. Changes in gain of the vertical component of the induced eye movements were expressed as a percentage of the preadapted values for the final analysis. Vertical aVOR gain changes were maximal in the position in which the gain had been adapted and declined progressively as subjects were moved from this position. Gain changes were plotted as a function of head orientation and fit with a sine function. The bias level of the fitted sines, i.e., the gravity-independent gain change, was –29±10% (SD). The gains varied around this bias as a function of head position by ±18±6%, which were the gravity-dependent gain changes. The gravity-dependent gain changes induced by only 1 h of adaptation persisted, gradually declining over several days. We conclude that there is a component of the vertical aVOR gain change in humans that is dependent on the head orientation in which the gain was adapted, and that this dependence can persist for substantial periods.     

Human 3-D aVOR with and without otolith stimulation

We describe in detail the frequency response of the human three-dimensional angular vestibulo-ocular response (3-D aVOR) over a frequency range of 0.05-1 Hz. Gain and phase of the human aVOR were determined for passive head rotations in the dark, with the rotation axis either aligned with or perpendicular to the direction of gravity (earth-vertical or earth-horizontal). In the latter case, the oscillations dynamically stimulated both the otolith organs and the semi-circular canals. We conducted experiments in pitch and yaw, and compared the results with previously-published roll data. Regardless of the axis of rotation and the orientation of the subject, the gain in aVOR increased with frequency to about 0.3 Hz, and was approximately constant from 0.3 to 1 Hz. The aVOR gain during pitch and yaw rotations was larger than during roll rotations. Otolith and canal cues combined differently depending upon the axis of rotation: for torsional and pitch rotations, aVOR gain was higher with otolith input; for yaw rotations the aVOR was not affected by otolith stimulation. There was a phase lead in all three dimensions for frequencies below 0.3 Hz when only the canals were stimulated. For roll and pitch rotations this phase lead vanished with dynamic otolith stimulation. In contrast, the horizontal phase showed no improvement with additional otolith input during yaw rotations. The lack of a significant otolith contribution to the yaw aVOR was observed when subjects were supine, prone or lying on their sides. Our results confirm studies with less-natural stimuli (off-vertical axis rotation) that the otoliths contribute a head-rotation signal to the aVOR. However, the magnitude of the contribution depends on the axis of rotation, with the gain in otolith-canal cross-coupling being smallest for yaw axis rotations. This could be because, in humans, typical yaw head movements will stimulate the otoliths to a much lesser extent then typical pitch and roll head movements.     

Human X-chromosomal lineages in Europe reveal Middle Eastern and Asiatic contacts

Within Europe, classical genetic markers, nuclear autosomal and Y-chromosome DNA polymorphisms display an east-west frequency gradient. This has been taken as evidence for the westward migration of Neolithic farmers from the Middle East. In contrast, most studies of mtDNA variation in Europe and the Middle East have not revealed clinal distributions. Here we report an analysis of dys44 haplotypes, consisting of 35 polymorphisms on an 8 kb segment of the dystrophin gene on Xp21, in a sample of 1203 Eurasian chromosomes. Our results do not show a significant genetic structure in Europe, though when Middle Eastern samples are included a very low but significant genetic structure, rooted in Middle Eastern heterogeneity, is observed. This structure was not correlated to either geography or language, indicating that neither of these factors are a barrier to gene flow within Europe and/or the Middle East. Spatial autocorrelation analysis did not show clinal variation from the Middle East to Europe, though an underlying and ancient east-west cline across the Eurasian continent was detected. Clines provide a strong signal of ancient major population migration(s), and we suggest that the observed cline likely resulted from an ancient, bifurcating migration out of Africa that influenced the colonizing of Europe, Asia and the Americas. Our study reveals that, in addition to settlements from the Near East, Europe has been influenced by other major population movements, such as expansion(s) from Asia, as well as by recent gene flow from within Europe and the Middle East.     

Genetic and genetic expression analyses of clear cell sarcoma of the kidney

Clear cell sarcoma of the kidney (CCSK) represents a significant diagnostic and clinical challenge. In search of diagnostically useful or biologically significant genetic abnormalities, we screened 30 CCSKs from the National Wilms Tumor Study Group. Genetic gains and losses were analyzed using comparative genomic hybridization; loss of heterozygosity at 11p15 was studied using microsatellite analysis. Loss of imprinting (LOI) was studied using allele-specific expression or methylation analysis at the ApaI polymorphic site for IGF2, AluI and RsaI sites for H19, and Cfo I site for SNRPN. Comparative genomic hybridization analysis revealed quantitative abnormalities in only 4 of 30 CCSKs. Two showed gain of 1q, one also showed loss of 10q, and the other also showed loss of terminal 4p. The other two cases demonstrated chromosome 19 loss and chromosome 19p gain, respectively. All 22 cases informative for 11p15 showed retention of both alleles. Of 14 CCSKs informative for IGF2, six showed biallelic expression; all three CCSKs informative for H19 exhibited monoallelic expression. The normal imprint pattern was present in all six CCSKs analyzed for SNRPN methylation. These data demonstrate an absence of consistent genetic gains or losses in CCSKs using these methods. The high frequency of LOI for IGF2 in CCSKs (43%) is comparable to that reported in Wilms tumors. The retention of imprinting at the SNRPN and H19 loci confirm that LOI is not a ubiquitous epigenetic change. This suggests that IGF2, a potent growth factor, may play a role in the development or progression of CCSK.     

Identification of protein pattern in kidney cancer using ProteinChip arrays and bioinformatics

Tumor biology of renal cell carcinoma (RCC) is not very well understood, although many studies on molecular and cellular biology have been performed. It is accepted now that cancer research has to be performed also with proteomic tools, because proteins are the real actors in the genesis and progression of cancer. Therefore, we used a ProteinChip System(R) (SELDI) which is able to detect minute amounts of protein and moreover to analyze a complex protein pattern. We analyzed 37 cases of clear cell RCC as a training set including corresponding normal tissue. From all samples protein lysates were made and spotted directly on different chip surfaces (SAX2, WCX). After a washing procedure the arrays were analyzed in the ProteinChip Reader. All profiles were subjected to a bioinformatical analysis including normalization, clustering, rule extraction and rating. Defined rules (markers) were evaluated using a test set of 24 samples (13 tumor tissues and 11 normal kidney tissues). The generated rule base for the SAX2 surface showed a sensitivity of 100% and a specificity of 97.3%. For the WCX arrays the optimal rule base showed worse results. A combined rule base for SAX2 and WCX did not result in a higher sensitivity or specificity. Using the optimal rule base for the SAX2 chip in the test set, sensitivity and specificity reached 76.9% and 100%, respectively. The ProteinChip System represents a key technology for the rapid detection of cancer specific proteomic patterns. It is possible to identify clear cell renal cancer with high sensitivity and specificity from minimal amounts of cells.     

Soft tissue pseudotumor following intramuscular injection of “DPT”: a pitfall in magnetic resonance imaging

We report the time-dependent magnetic resonance imaging (MRI) changes that resulted from an intramuscular injection of a commonly-used pediatric sedation regimen (DPT). These changes at the site of injection consist of a focal abnormality characterized by a slight increase in signal intensity on T1 weighted images and markedly increased signal intensity on T2 weighted images. Alterations in signal are detectable almost immediately after the injection and progress over the first 31 hours. This abnormality, which could be mistaken for real disease, persists up to 36 days following injection.     

Postmortem Stability of SARS-CoV-2 in Nasopharyngeal Mucosa

Analyses of infection chains have demonstrated that severe acute respiratory syndrome coronavirus 2 is highly transmissive. However, data on postmortem stability and infectivity are lacking. Our finding of nasopharyngeal viral RNA stability in 79 corpses showed no time-dependent decrease. Maintained infectivity is supported by virus isolation up to 35 hours postmortem.