Predictive factors for hematopoietic engraftment after autologous peripheral blood stem cell transplantation for AL amyloidosis

Treatment of patients with AL amyloidosis with high-dose melphalan and autologous peripheral blood stem cells (PBSC) produces hematologic remissions in approximately 40% of evaluable patients, accompanied by improvements in organ disease and quality of life. These patients, who frequently have amyloid deposits in bone marrow blood vessels and interstitium and impaired function of kidneys, liver, spleen, and heart, represent an unusual population for stem cell transplantation, with unique problems. To identify factors influencing engraftment rates after chemotherapy and autologous granulocyte colony-stimulating factor (G-CSF)-mobilized PBSC reinfusion, we studied a group of 225 patients. The median time to neutrophil engraftment was 10 days (range, 8-17 days). In a multivariate analysis, the factors positively affecting the rate of neutrophil engraftment were CD34+ stem cell dose, female gender, and minimal prior alkylator therapy. The median time to platelet engraftment was 13 days (range, 7-52 days). Factors positively affecting platelet engraftment, in addition to CD34+ cell dose, included preserved renal function and the absence of neutropenic fever. The conditioning dose of intravenous melphalan was not found to be an independent predictive factor for hematopoietic recovery. Thus, in this patient population, organ function and host and hematopoietic factors influence engraftment after PBSC rescue.     

Pathogenesis of acute renal failure following temporary renal ischemia in the rat.

In this study, we characterized the sequence of several intrarenal events and evaluated their relative importance in the pathogenesis of unilateral oliguric acute renal failure induced experimentally in rats by complete occlusion of a renal artery for 1 hour. Kidneys were studied prior to occlusion and 1-3 hours and 22-26 hours after release of the temporary occlusion. Renal blood flow measured by an electromagnetic flow transducer was reduced to 40-50% of control during both postocclusion periods. Flow of tubular fluid was markedly reduced, and the damaged kidneys were oliguric. Proximal and distal convolutions were filled with fluid and dilated 1-3 hours after occlusion; their pressures were greatly heterogeneous and were elevated, on the average, to 31 and 16 mm Hg, respectively. Glomerular capillary pressure at this time was normal or slightly increased. Histological sections showed extensive tubular obstruction. We conclude that initially the oliguria is primarily due to intraluminal obstruction in the absence of predominant increases in preglomerular vascular resistance. Observations at 22-26 hours after occlusion indicated acute tubular necrosis. Moreover, the combined involvement of preglomerular vasoconstriction, presisting tubular obstruction, and passive backflow of tubular fluid appeared to be important in the maintenance of the oliguria. Glomerular capillary, proximal intratubular, and peritubular capillary hydrostatic pressures were reduced below control values. After acute volume expansion, the reduced pressures and renal blood flow were reversed, yet the experimental kidneys remained oliguric. Thus, it is clear that tubular obstruction is a significant factor responsible for both the genesis and the maintenance of oliguria in this experimental model of ischemia-induced acute renal failure.     

P300, Disinhibited Personality, and Early-Onset Alcohol Problems

BACKGROUND: Recent research suggests that a reduced P300 amplitude of the event-related potential is associated with a vulnerability to alcoholism. This study tested the hypothesis that reductions in the P300 amplitude would be associated with specific dimensions of disinhibited personality (social deviance proneness and impulsivity) and that these personality traits would mediate the association between P300 and alcohol problems in a young adult sample that varied widely in disinhibitory traits. METHODS: Alcohol problems, personality (impulsivity, social deviance, harm avoidance, and excitement seeking), and event-related potentials were measured in a sample of 190 subjects (87 men, 103 women) with a mean age of 20.7 +/- 1.9 years. RESULTS: Social deviance, impulsivity, and alcohol problems were associated with reductions in the P300, but only in male subjects. A structural model suggested that social deviance, impulsivity, and alcohol problems were all strongly related to P300 amplitude at Fz. Further analyses indicated that for male subjects, social deviance mediated the association between P300 at Fz and alcohol problems as well as the association between impulsivity and alcohol problems. CONCLUSIONS: This study suggests that reduced P300s are strongly associated with a general tendency toward antisocial, defiant, and impulsive traits, which might, in turn, increase the risk for alcohol abuse. The lack of an association between reduced P300s and personality or alcohol problems in women was unexpected and deserves further study.     

Eating one's words,Part II: the embodied mind and reflective function in anorexia nervosa—theory

Anorexia nervosa as a psychiatric disorder presents itself through the concreteness of symptoms. Emotions are experienced as a corporeality here‐and‐now. In a companion article, Part I, different ‘body metaphors’ are described and categorised. The human body functions as metaphor, and in anorexia nervosa there is a striking closeness between emotions and different bodily experiences. This is interpreted as impaired ‘reflective function’, referring to the capacity to make mental representations, and is proposed as a central psychopathological feature. The psychodynamic concepts ‘concretised metaphors’ and ‘psychic equivalence’ are discussed as useful tools to better understand such compromised symbolic capacity. Psychotherapy in anorexia nervosa can be described as a relational process where concretised metaphors will be developed into genuine linguistic ones. Part III in this series of articles presents an outline for psychotherapy for anorexia nervosa. Copyright © 2007 John Wiley & Sons, Ltd and Eating Disorders Association.     

Septic arthritis of the C1-C2 lateral facet joint and torticollis: pseudo-Grisel's syndrome

We present the case of a 76-year-old man who experienced the sudden development of fever, rightsided neck pain and stiffness, and torticollis. A soft tissue mass was noted on the right side of his neck, but his head was tilted to the left. Computed tomography scans (with reformatted sagittal and coronal images) of the patient's cervical spine revealed destructive changes of the right lateral masses of C1 and C2 and the clivus, and a well-delineated peridontoid soft tissue mass (confirmed by magnetic resonance imaging). After the second episode of right-sided hemiparesis, he underwent transoral surgical exploration, with anterior decompression and odontoidectomy. Histologic examination of the surgical material revealed granulation tissue, fibrosis, and chronic inflammation, consistent with abscess formation with invasion and compression of the spinal cord and bone. This case suggests that nonreducible rotational head tilt to the side opposite the side of lateral mass collapse should raise the suspicion of a possible infection.     

Determinants of hypoxic contracture in isolated heart muscle preparations.

Further studies on hypoxic contracture are described, using resting and contracting isolated muscle preparations from several species. The effect of temperature, pH, substrate, calcium concentration, osmolality and inotropic interventions was explored. The 'protective' effect of acidosis was not contingent on its negative inotropic influence. No evidence was adduced that hypoxic contracture can be modulated other than by altering energy supply or demand. The study does not discriminate between rigor and rised cytosolic calcium as mechanisms causing hypoxic contracture, but demonstrates that hypoxic contracture is not directly dependent on the availability of intracellular calcium.     

Competition between T cells maintains clonal dominance during memory inflation induced by MCMV

Both human cytomegalovirus (HCMV) and murine cytomegalovirus (MCMV) establish persistent infections that induce the accumulation of virus‐specific T cells over time in a process called memory inflation. It has been proposed that T cells expressing T‐cell receptors (TCRs) with high affinity for HCMV‐derived peptides are preferentially selected after acute HCMV infection. To test this in the murine model, small numbers of OT‐I transgenic T cells, which express a TCR with high affinity for the SIINFEKL peptide, were transferred into congenic mice and recipients were challenged with recombinant MCMV expressing SIINFEKL. OT‐I T cells were selectively enriched during the first 3 weeks of infection. Similarly, in the absence of OT‐I T cells, the functional avidity of SIINFEKL‐specific T cells increased from early to late times postinfection. However, even when exceedingly small numbers of OT‐I T cells were transferred, their inflation limited the inflation of host‐derived T cells specific for SIINFEKL. Importantly, subtle minor histocompatibility differences led to late rejection of the transferred OT‐I T cells in some mice, which allowed host‐derived T cells to inflate substantially. Thus, T cells with a high functional avidity are selected shortly after MCMV infection and continuously sustain their clonal dominance in a competitive manner.     

Integrating micro CT indices,CT imaging and computational modelling to assess the mechanical performance of fluoride treated bone

In this study we evaluate the influence of low-dose fluoride treatment on 23 patient biopsies. Computational finite element (FE) models of each biopsy were subjected to a range of loads including compression, shear and torsion. The modelling framework was validated against three 3D printed models with known material properties subjected to compression till failure using an Instron machine. The primary outcomes from this study were that mechanical strength was not significantly correlated to low-dose (<10 mg/day) of fluoride levels (one-way ANOVA, P-values of 0.78, 0.69 and 0.62 for compression, shear and torsion, respectively). However, when bulk bone material properties were derived from DXA bone mineral density (BMD) from each patient's proximal femur a non-significant linear decline in mechanical strength with increase in fluoride was predicted. When the same material property was used for all bones (to evaluate bone architecture influence) then mechanical strength showed a characteristic concave upwards trend, consistent with the variation of micro CT derived percentage bone volume (BV/TV). The secondary outcomes from this study were that in compression, BV/TV was observed to be a strong surrogate measure for mechanical strength (R² = 0.83), while bone surface density (R² = 0.6), trabecular thickness (R² = 0.5) and intersection surface (R² = 0.6) also explained the variation of mechanical strength well. However, trabecular separation and trabecular number were mildly correlated with mechanical strength (R² of 0.31 and 0.35, respectively). Compression was the loading mode most strongly correlated to micro CT indices. Material properties adapted from the proximal femur reduced the CT index correlations by up to 58% indicating that bulk density from a near proximity is a poor representation of specific localised density. Substituting the 3D micro CT indices with 2D histomorphometric data decreased correlations by at least 33% indicating that structural identification on a plane is not representative of the full 3D architecture necessary for a complete bone strength analysis. The presented computational framework may be used to assess the roles that bone architecture and loading modes play in bone quality, and which micro CT indices are good surrogate measures for mechanical strength.