A review of spinal injuries in the invasive cardiologist: part 1. Biomechanics and pain generation

This review provides a perspective of spinal injuries related to invasive cardiology, an understanding of the anatomy and physiology of the spine, the etiology and pathophysiology of spinal injuries, and options for prevention and treatment. Because of the breadth of this review, it has been divided into two parts with the first describing the biomechanics and generation of back pain and the second discussing treatment options and prevention of back injury. A comprehensive overview of the biomechanics of the spine from the individual vertebral unit to the complex motions involved in everyday life is reviewed. The significant intrinsic and extrinsic factors playing a role in the mechanism of disc damage, including occupational hazards encountered by the invasive cardiologist, are discussed. We also address the mechanisms of pain generation in the spine and the role that inflammation plays, which explains the presence of symptoms with little or no detectable pathology on imaging studies.     

The Therapeutic Alliance and CBASP-Specific Skill Acquisition in the Treatment of Chronic Depression

This study examined the influences of proposed specific and common psychotherapeutic factors in a sample of chronically depressed adult outpatients. Participants (N = 324) were drawn from a multi-site clinical trial that compared the efficacies of the cognitive behavioral analysis system of psychotherapy (CBASP), nefazodone, and their combination. This report is limited to patients receiving CBASP alone or combination treatment. A series of regression analyses were performed to test whether: (1) the ability to utilize the skills taught in CBASP mediated the relationship between the early therapeutic alliance and endpoint depression, and (2) the therapeutic alliance moderated the relationship between skill utilization and endpoint depression. Neither model was supported. Instead, each of these factors contributed independently and additively to alleviation of depressive symptoms.     

Ectopic Production of the Isolated Beta Subunit of Human Chorionic Gonadotropin

A material similar to the beta subunit of human chorionic gonadotropin (hCG-β) was detected in serum (300 ng/ml) and tumor extract from a 75-yr-old man with pancreatic adenosquamous carcinoma. This material was indistinguishable from hCG-β in three different types of radioimmunoassay that displayed widely varying reactions with glycoprotein trophic hormones and their subunits. In gel chromatography there appeared to be heterogeneity of the serum beta-like immunoactivity, including one component that coeluted with standard hCG-β tracer and another immunologically indistinguishable component that displayed a slightly lower elution volume. Neither complete human chorionic gonadotropin (hCG) nor its alpha subunit was detected in radioimmunoassays of serum, before or after fractionation, or in tumor extract. The absence of complete hCG was confirmed in a gonadotropin bioassay sensitive to 15 ng of hCG, which showed no bioactivity in serum or tumor extract containing 450 and 90 ng of hCG-β, respectively. This case probably represents the first demonstration of isolated polypeptide subunit production of ectopic origin and suggests that hCG-β, as well as other subunits, may prove useful as cancer markers.     

Lactic Acidosis as a Result of Iron Deficiency

Iron-deficient rats have an impaired work performance, even when their anemia is corrected by exchange transfusion. Muscle activity is associated with a higher blood lactate concentration than is observed in iron-replete animals. The accumulation of lactate is a result of excessive production as lactate clearance from the blood was shown to be unaffected. By adjusting the work load to a lower level, it was possible to divide iron-deficient animals into two groups, one capable of continued treadmill running and another in which animals stopped before 20 min. In the former, blood lactate concentration reached a plateau at moderate levels, whereas it continued to increase in the latter until the animal stopped running. Levels of alpha-glycerophosphate oxidase in skeletal muscle mitochondria were found to be much lower in the second group (P < 0.001). Lactate infusion into normal animals was shown to interfere with work performance, and maintenance of a normal pH in iron-deficient and iron-replete animals did not prevent the impairment in work associated with high blood lactate concentrations. Additional evidence was obtained that energy substrate (blood glucose and free fatty acids, muscle glycogen) was adequate in irondeficient animals. Oxygen tension in their vena caval blood was higher than in controls. Furthermore, the in situ behavior of electrically stimulated gastroenemius and soleus muscles appeared similar to that of control animals. Because the stimulation of the single muscle in the iron-deficient animal did not result in appreciable elevation of blood lactate and did not show impaired contractility further supported the hypothesis that the elevation of blood lactate caused the decreased work performance. It is concluded that iron deficiency by a depletion in the iron-containing mitochondrial enzyme, alpha-glycerophosphate oxidase, impairs glycolysis, resulting in excess lactate formation, which at high levels leads to cessation of physical activity.     

TWEAK induces liver progenitor cell proliferation

Progenitor ("oval") cell expansion accompanies many forms of liver injury, including alcohol toxicity and submassive parenchymal necrosis as well as experimental injury models featuring blocked hepatocyte replication. Oval cells can potentially become either hepatocytes or biliary epithelial cells and may be critical to liver regeneration, particularly when hepatocyte replication is impaired. The regulation of oval cell proliferation is incompletely understood. Herein we present evidence that a TNF family member called TWEAK (TNF-like weak inducer of apoptosis) stimulates oval cell proliferation in mouse liver through its receptor Fn14. TWEAK has no effect on mature hepatocytes and thus appears to be selective for oval cells. Transgenic mice overexpressing TWEAK in hepatocytes exhibit periportal oval cell hyperplasia. A similar phenotype was obtained in adult wild-type mice, but not Fn14-null mice, by administering TWEAK-expressing adenovirus. Oval cell expansion induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) was significantly reduced in Fn14-null mice as well as in adult wild-type mice with a blocking anti-TWEAK mAb. Importantly, TWEAK stimulated the proliferation of an oval cell culture model. Finally, we show increased Fn14 expression in chronic hepatitis C and other human liver diseases relative to its expression in normal liver, which suggests a role for the TWEAK/Fn14 pathway in human liver injury. We conclude that TWEAK has a selective mitogenic effect for liver oval cells that distinguishes it from other previously described growth factors.     

Soluble and Membrane-bound Forms of Signaling Lymphocytic Activation Molecule (SLAM) Induce Proliferation and Ig Synthesis by Activated Human B Lymphocytes

In this study it is shown that both membrane-bound and soluble forms of signaling lymphocytic activation molecule (SLAM) induce proliferation and Ig synthesis by activated human B cells. Activated B cells express the membrane-bound form of SLAM (mSLAM), the soluble (s) and the cytoplasmic (c) isoforms of SLAM, and the expression levels of mSLAM on B cells are rapidly upregulated after activation in vitro. Importantly, recombinant sSLAM and L cells transfected with mSLAM efficiently enhance B cell proliferation induced by anti-μ mAbs, anti-CD40 mAbs or Staphylococcus aureus Cowan I (SAC) in the presence or absence of IL-2, IL-4, IL-10, IL-12, or IL-15. sSLAM strongly enhances proliferation of both freshly isolated B cells and B cells derived from long-term in vitro cultures, indicating that SLAM acts not only during the initial phase of B cell activation but also during the expansion of preactivated B cells. In addition, sSLAM enhances production of IgM, IgG, and IgA by B cells activated by antiCD40 mAbs. SLAM has recently been shown to be a high affinity self-ligand, and the present data suggest that signaling through homophilic SLAM–SLAM binding during B–B and B–T cell interactions enhances the expansion and differentiation of activated B cells.     

Thyroid-Stimulating Activity and Chorionic Gonadotropin

The nature of the substance with thyroid-stimulating activity (TSA) present in human chorionic gonadotropin (hCG) prepared from pregnancy urine was investigated. In the mouse thyrotropin bioassay, the characteristic maximum of blood radioactivity obtained with the TSA in hCG preparations occurred after that obtained with pituitary thyrotropin (hTSH) but before that obtained with long-acting thyroid stimulator. Antiserum to the alpha subunit of hCG produced significant neutralization of the TSA in hCG. Significant antagonism of hTSH biologic activity was achieved with certain doses of hCG, suggesting that the TSA in hCG was a partial agonist of hTSH. This antagonism was neutralized by antiserum to the beta subunit of hCG. These immunologic results suggest that the substance with TSA in hCG preparations contains antigenic determinants similar to those of both the alpha and the beta subunit of hCG. Amounts of highly purified hCG and crude commercial hCG of equal immunologic activity were biologically indistinguishable in the bioassay for TSA. Both hCG immunoreactivity and the TSA in hCG adsorbed to concanavalin A and eluted with 0.2 M methyl alpha-D-glucopyranoside. These results are consistent with the hypothesis that TSA is an intrinsic property of hCG or of a glycoprotein molecule physicochemically, biologically, and immunologically similar to hCG.     

Intramural vesicular fat--an uncommon CT finding

We present a case of a 75-year-old male who presented with lower back pain found to have an incidental finding of intramural vesicular fat on an unenhanced computed tomography of the pelvis. This relatively uncommon finding of a normal entity should not be mistaken for other causes of pathology within the urinary bladder.