Numerical solution for blood flow in a centrifugal ventricular assist device

A very small centrifugal pump, fully supported by magnetic bearings, is being developed for use as a ventricular assist device to be implanted in humans. In this paper, we apply computational fluid dynamics to model the blood flow to aid in the design of the ventricular assist device. The flow of blood through the pump has been modeled using computational fluid dynamics (CFD) software that is commercially available from AEA Technology, UK. The flow regions modeled in version 3 of the Continuous Flow Ventricular Assist Device (CF3) are the fully shrouded four bladed impeller and the two clearance regions around the impeller that are bounded by the pump hub and shroud. This paper describes the geometry and computational grids developed for the flow regions, and the equations of motion for the blood flow are developed. The overall numerically-evaluated flow rates and head rise have similar trends to the flow parameters experimentally measured, indicating that future pump designs can be effectively modeled numerically before being constructed and tested. Numerical solutions are presented and compared with experimentally-obtained overall pump performance results. These solutions are used to predict shear stress levels to be experienced by the blood flowing through the pump, and it is predicted that hemolysis will be insignificant. The solutions also indicate no regions of flow stagnation that can be a source of thrombosis in pumps. The calculations provide a viable design method to achieve improved efficiency in future versions of this pump.     

The locus of enterocyte effacement (LEE)-encoded regulator controls expression of both LEE- and non-LEE-encoded virulence factors in enteropathogenic and enterohemorrhagic Escherichia coli

Regulation of virulence gene expression in enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) is incompletely understood. In EPEC, the plasmid-encoded regulator Per is required for maximal expression of proteins encoded on the locus of enterocyte effacement (LEE), and a LEE-encoded regulator (Ler) is part of the Per-mediated regulatory cascade upregulating the LEE2, LEE3, and LEE4 promoters. We now report that Ler is essential for the expression of multiple LEE-located genes in both EPEC and EHEC, including those encoding the type III secretion pathway, the secreted Esp proteins, Tir, and intimin. Ler is therefore central to the process of attaching and effacing (AE) lesion formation. Ler also regulates the expression of LEE-located genes not required for AE-lesion formation, including rorf2, orf10, rorf10, orf19, and espF, indicating that Ler regulates additional virulence properties. In addition, Ler regulates the expression of proteins encoded outside the LEE that are not essential for AE lesion formation, including TagA in EHEC and EspC in EPEC. delta ler mutants of both EPEC and EHEC show altered adherence to epithelial cells and express novel fimbriae. Ler is therefore a global regulator of virulence gene expression in EPEC and EHEC.     

Elevated catecholamines during cardiac surgery: consequences of reperfusion of the postarrested heart

This study determines whether reperfusion of the heart with elevated blood levels of epinephrine (E) and norepinephrine (NE) during cardiac surgery produces deleterious effects. The study was conducted in 60 patients undergoing coronary artery bypass surgery. Arterial catecholamine values increased significantly (p less than 0.05), from prebypass control levels of 152 +/- 29 and 327 +/- 30 pg/ml of E and NE, respectively, to 415 +/- 78 and 554 +/- 49 pg/ml, at initiation of perfusion of the heart after the aortic cross-clamp was removed. Serial measurement of arterial (A) and coronary sinus (CS) E, NE, potassium, lactate, PO2 and CK-MB revealed that during 10 minutes of reperfusion the heart extracted E (positive A-CS difference, p less than 0.05), but that the NE A-CS difference was 0. The CS effluent contained significantly (p less than 0.05) higher concentrations of potassium, lactate and CK-MB during reperfusion than before aortic occlusion. There was no significant correlation of arterial E and NE, CS E and NE or A-CS differences in E and NE with myocardial release of lactate, potassium or CK-MB. There was a weak association (r = 0.4, p less than 0.01) between coronary sinus CK-MB and aortic occlusion time. Maximal arterial E and NE values did not correlate with 10-hour postoperative (maximal) CK-MB values. These results indicate that reperfusion of the postarrested ischemic heart with high levels of endogenously released catecholamines does not worsen ischemia or contribute significantly to myocardial damage.     

Analysis of a surface protein of Streptococcus pneumoniae recognised by protective monoclonal antibodies

Using two monoclonal antibodies which protect mice from a fatal challenge with S. pneumoniae, we have identified a surface protein antigen on the pneumococcus. These antibodies recognised components of 84 and 76 kD in a cell wall extract of the nonencapsulated strain, R36A, against which they were made. Absorption experiments indicated that both of the antibodies recognised the same two proteins. The proteins detected by the antibodies in the encapsulated type 2 strain D39 and type 3 strain WU2, exhibited different molecular weights than those proteins detected from R36A. Using a colony blot procedure and a quantitative ELISA, we have shown that these antibodies react with 6 of the 21 pneumococcal strains tested. There was no association between reactivity with these anti-protein antibodies and the capsular serotype of the pneumococcal isolates tested.     

Pneumococcal surface protein A (PspA) is serologically highly variable and is expressed by all clinically important capsular serotypes of Streptococcus pneumoniae.

Pneumococcal surface protein A (PspA) has been shown previously to elicit antibodies protective against pneumococcal infection and to be necessary for full pneumococcal virulence in mice. The protein was originally defined by the two mouse monoclonal antibodies Xi64 and Xi126, which together recognized PspA on 14% of pneumococcal isolates. Some PspA molecules reacted with both antibodies, but most reacted with only one or the other. In the present study we demonstrated that PspA is produced by all pneumococci, confirming our hypothesis that there are variants of PspA which are not detected by Xi64 and Xi126. We produced a rabbit antiserum and five additional monoclonal antibodies specific for PspA for these studies. The rabbit antiserum reacted with each of 95 pneumococcal isolated tested, comprising 16 capsular serotypes. One or more of the seven monoclonal anti-PspA antibodies reacted with 95% (53 of 57) of pneumococcal isolates tested. The specificity of the monoclonal and polyclonal antibodies to PspA was confirmed in two ways: (i) by detection of molecules on wild-type pneumococci that are identical in molecular weight to those detected in Western blots (immunoblots) with Xi64 and Xi126 and (ii) by the use of mutants of Streptococcus pneumoniae that fail to produce PspA or that produce a truncated form of PspA. By using the seven monoclonal antibodies, we observed 31 PspA types among the 57 isolates. When the 53 strains reactive with the monoclonal antibodies were analyzed by capsular type as well as by serologic type and molecular weight of PspA, we observed 50 different clonotypes of pneumococci.     

MR imaging of facial nerve enhancement in Bell palsy or after temporal bone surgery

The authors evaluated magnetic resonance (MR) images obtained with intravenously administered gadolinium in ten patients who had facial paralysis and no facial nerve tumor. In patients with either Bell palsy (four patients) or facial paralysis after temporal bone surgery (six patients), intratemporal facial nerve enhancement was seen. Facial nerve enhancement on MR images proved to be a nonspecific finding.     

Effects of sex and age on bone microstructure at the ultradistal radius: a population-based noninvasive in vivo assessment.

In a population-based cross-sectional study, we examined effects of sex and age on bone microstructure at the wrist using high-resolution 3-D pQCT. Compared with women, men had thicker trabeculae in young adulthood and had less microstructural damage with aging. These findings may contribute to the virtual immunity of men to age-related increases in wrist fractures. INTRODUCTION: Although changes in bone microstructure contribute to fracture risk independently of BMD, it has not heretofore been possible to assess this noninvasively in population-based studies. MATERIALS AND METHODS: We used high-resolution 3-D pQCT imaging (voxel size, 89 mum) to define, in a random sample of women (n = 324) and men (n = 278) 21-97 years of age, sex and age effects on bone microstructure at the wrist. RESULTS: Relative to young women (age, 20-29 years), young men had greater trabecular bone volume/tissue volume (BV/TV; by 26%, p = 0.001) and trabecular thickness (TbTh; by 28%, p < 0.001) but similar values for trabecular number (TbN) and trabecular separation (TbSp). Between ages 20 and 90 years, cross-sectional decreases in BV/TV were similar in women (-27%) and in men (-26%), but whereas women had significant decreases in TbN (-13%) and increases in TbSp (+24%), these parameters had little net change over life in men (+7% and -2% for TbN and TbSp, respectively; p < 0.001 versus women). However, TbTh decreased to a greater extent in men (-24%) than in women (-18%; p = 0.010 versus men). CONCLUSIONS: Whereas decreases with age in trabecular BV/TV are similar in men and women, the structural basis for the decrease in trabecular volume is quite different between the sexes. Thus, over life, women undergo loss of trabeculae with an increase in TbSp, whereas men begin young adult life with thicker trabeculae and primarily sustain trabecular thinning with no net change in TbN or TbSp. Because decreases in TbN have been shown to have a much greater impact on bone strength compared with decreases in TbTh, these findings may help explain the lower life-long risk of fractures in men, and specifically, their virtual immunity to age-related increases in distal forearm fractures.     

Prediction of wound healing in human diabetic foot ulcers by diffuse near‐infrared spectroscopy: A pilot study

A human study was conducted in which the efficacy of in vivo diffuse near‐infrared (NIR) spectroscopy was demonstrated in predicting wound healing in diabetic foot ulcers. Sixteen chronic diabetic wounds were followed and assessed for subsurface oxy‐hemoglobin concentration using the NIR device. Weekly measurements were conducted until there was wound closure, limb amputation, or 20 completed visits without healing. Digital photography measured wound size, and the degree of wound contraction was compared with the NIR results. In the 16 patients followed, seven wounds healed, six limbs were amputated, and three wounds remained opened after 20 visits. The initial values in subsurface hemoglobin concentration in all wounds were higher than the nonwound control sites. Healed wounds showed a consistent reduction of hemoglobin concentration several weeks before closure that approached control site values. In wounds that did not heal or resulted in amputation of the limb, the hemoglobin concentration remained elevated. In some cases, these nonhealing wounds appeared to be improving clinically. A negative slope for the rate of change of hemoglobin concentration was indicative of healing across all wounds. In conclusion, evaluation of wounds using NIR may provide an effective measurement of wound healing. NIR spectroscopy can determine wound healing earlier than that visibly assessed by current clinical approaches.