Superior vena cava syndrome and syncope in an implantable cardioverter defibrillator recipient.

We describe the case of a recipient of an implantable cardioverter defibrillator with multiple syncopal episodes due both to superior vena cava obstruction and electrical instability. These complications occurred in the presence of two transvenous implantable cardioverter defibrillator leads. The patient has been managed conservatively with anticoagulants and new antiarrhythmic drugs with improvement in both his clinical problems.     

Mechanism of UV-related carcinogenesis and its contribution to nevi/melanoma

Melanoma consists 4-5 % of all skin cancers, but it contributes to 71-80 % of skin cancers deaths. UV light affects cell and tissue homeostasis due to its damaging effects on DNA integrity and modification of expression of a plethora of genes. DNA repair systems protect cells from UV-induced lesions. Several animal models of melanoma have been developed (Xiphophorus, Opossum Monodelphis domestica, mouse models and human skin engrafts into other animals). This review discusses possible links between UV and genes significantly related to melanoma but does not discuss melanoma genetics. These include oncogenes, tumor suppressor genes, genes related to melanocyte-keratinocyte and melanocyte-matrix interaction, growth factors and their receptors, CRH, ACTH, α-MSH, glucocorticoids, ID1, NF-kappaB and vitamin D3.     

Lymphocyte subpopulations in middle ear effusions: flow cytometry analysis.

OBJECTIVE: The aim of this study was to identify lymphocyte subpopulations in middle ear effusions, peripheral blood, and adenoids in children suffering from otitis media with effusion. SETTING: Tertiary referral center. PATIENTS: Thirty-three children (55 ears) undergoing myringotomy for otitis media with effusion. METHODS: CD3, CD4, CD8, CD19, and natural killer cell populations were investigated in middle ear effusion, peripheral blood, and adenoids using a three-color monoclonal antibody and flow cytometry method for quantitative estimation. RESULTS: T cells (CD3) are dominating lymphocytes in middle ear effusion. Among T lymphocytes, the majority are those of the helper type (CD4). The dominating isoform among CD4 lymphocytes are memory cells (CD4CD45RO); among CD8 lymphocytes, naive cells (CD8CD45RA). The percentage of CD4 cells, CD8 cells, and the CD4/CD8 ratio was significantly higher in middle ear effusions than in blood. The percentage of memory CD4 lymphocytes and naive CD8 lymphocytes was significantly lower in the middle ear effusion. Lymphocyte subsets were compared between 22 pairs of effusions from each patient. The percentage of each type of cell did not differ significantly. CONCLUSION: The results of this study indicate local regulation of the lymphocyte profile in middle ear effusions and the same phase of immune response in two ears of the same patient.     

Astrocytic induction of matrix metalloproteinase-9 and edema in brain hemorrhage.

We tested the hypothesis that astrocytic matrix metalloproteinase-9 (MMP-9) mediates hemorrhagic brain edema. In a clinical case of hemorrhagic stroke, MMP-9 co-localized with astrocytes and neurons in peri-hematoma areas. In a mouse model where blood was injected into striatum, MMP-9 was colocalized with astrocytes surrounding the hemorrhagic lesion. Because MMP-9 is present in blood as well as brain, we compared four groups of wild type (WT) and MMP-9 knockout (KO) mice: WT blood injected into WT brain, KO blood into KO brain, WT blood into KO brain, and KO blood into WT brain. Gel zymography showed that MMP-9 was elevated in WT hemorrhagic brain tissue but absent from KO hemorrhagic brain tissue. Edematous water content was elevated when WT blood was injected into WT brain. However, edema was ameliorated when MMP-9 was absent in either blood or brain or both. To further assess the mechanisms involved in astrocytic induction of MMP-9, we next examined primary mouse astrocyte cultures. Exposure to hemoglobin rapidly upregulated MMP-9 in conditioned media within 1 to 24 h. Hemoglobin-induced MMP-9 was reduced by the free radical scavenger U83836E. Taken together, these data suggest that although there are large amounts of MMP-9 in blood, hemoglobin-induced oxidative stress can trigger MMP-9 in astrocytes and these parenchymal sources of matrix degradation may also be an important factor in the pathogenesis of hemorrhagic brain edema.     

Mechanisms of opioid-induced tolerance and hyperalgesia.

Opioid tolerance and opioid-induced hyperalgesia are conditions that negatively affect pain management. Tolerance is defined as a state of adaptation in which exposure to a drug induces changes that result in a decrease of the drug's effects over time. Opioid-induced hyperalgesia occurs when prolonged administration of opioids results in a paradoxic increase in atypical pain that appears to be unrelated to the original nociceptive stimulus. Complex intracellular neural mechanisms, including opioid receptor desensitization and down-regulation, are believed to be major mechanisms underlying opioid tolerance. Pain facilitatory mechanisms in the central nervous system are known to contribute to opioid-induced hyperalgesia. Recent research indicates that there may be overlap in the two conditions. This article reviews known and hypothesized pathophysiologic mechanisms surrounding these phenomena and the clinical implications for pain management nurses.     

Evaluation of 188 consecutive homografts implanted in pulmonary position after 20 years.

OBJECTIVE: Homografts are considered the gold standard for right ventricular outflow tract reconstruction. Their long-term durability is limited, and alternatives became available. We evaluate their long-term hemodynamic performance to permit comparisons with alternative devices. METHODS: Between 1985 and 2004, 188 homografts were implanted in pulmonary position at our institution. Mean patient age was 24.8 years (range 2 days-75 years); 56 were female and 132 male. Total follow-up time was 1073 years. Fifty-eight percent were Ross procedures (mean age 31.5 years) and 42% were different procedures (mean age 15.6 years); main diagnoses were tetralogy of Fallot (48%), truncus arteriosus (14%), transposition of the great arteries (11%). Twenty-six percent were redo implantations. We evaluated freedom from death, explantation, insufficiency, relevant gradient, degeneration, and the interval between diagnosis of degeneration and therapeutic procedure (therapeutic gap). Results were stratified by indication, age, history, homograft size, and origin. RESULTS: Ten-year-freedom-from explantation was 82% in homografts >19 mm and 45% in smaller ones. Ten-year freedom from degeneration was 68% after Ross procedure and 25% after other operations; it was 83% in patients older than 10 years at implantation and 51% in younger ones. 'Non-Ross-procedure' and 'implantation age below 10 years' were the only independent risk factors for degeneration. The observed trend towards therapeutical gap reduction was not statistically significant. CONCLUSIONS: Homograft implantation in the pulmonary position can be performed with good long-term freedom from explantation. However, freedom from degeneration is a matter of concern. Therefore, alternative valved conduits are required especially for pediatric patients.     

The role of quinone reductase (NQO1) and quinone chemistry in quercetin cytotoxicity.

The effects of quercetin on viability and proliferation of Chinese Hamster Ovary (CHO) cells and CHO cells overexpressing human quinone reductase (CHO+NQO1) were studied to investigate the involvement of the pro-oxidant quinone chemistry of quercetin. The toxicity of menadione was significantly reduced in CHO+NQO1 cells compared to wild-type CHO cells, validating the NQO1-overexpression in the CHO+NQO1 transfectant. Quercetin inhibited the proliferation of wild-type CHO and CHO+NQO1 cells to a similar extent without affecting cell viability, indicating that NQO1 enrichment of CHO cells did not provide increased protection. On the other hand, inhibition of NQO1 in both types of cells by dicoumarol significantly potentiated the inhibitory effect of quercetin on cell proliferation, revealing the role of NQO1 in cellular protection against quercetin. Altogether, these results can be explained by the hypothesis that both wild-type CHO and CHO+NQO1 cells contain sufficient NQO1 activity for optimal protection against the pro-oxidant effect of quercetin on cell proliferation. The results also point at a cellular NQO1 threshold for optimal protection against quercetin. This NQO1 threshold seems to be in the range of NQO1 activities already present in various tissues.     

The synthesis and localization of alternatively spliced fibronectin EIIIB in resting and thrombin-treated megakaryocytes

There are several species of alternatively spliced fibronectin (FN). One of these, FN EIIIB, is primarily present in embryonic and in proliferating and migrating cells and is believed to be important for cell maturation. We have studied the synthesis, localization, and secretion of this FN isoform in isolated guinea pig megakaryocytes, nonmegakaryocytic bone marrow cells, and platelets. There was 7.5 times more general FN in megakaryocytes than in nonmegakaryocytic cells based on the analysis of equivalent amounts of protein. FN EIIIB was detected by Western blotting in megakaryocytes but not in nonmegakaryocytic cells present in bone marrow. Neither megakaryocytes nor platelets secreted FN EIIIB, while megakaryocytes secreted 25.3% +/- 4.6% general FN and platelets secreted about 61% general FN in response to thrombin. Analysis of immunostained cells by confocal microscopy revealed that FN EIIIB had been redistributed to the surface of megakaryocytes in response to thrombin. Synthesis was studied by metabolic labeling, and megakaryocytes were shown to synthesize FN and FN EIIIB. Thus, megakaryocytes and platelets are among a small number of adult cells and tissues that synthesize and contain FN EIIIB. The expression of FN EIIIB on the megakaryocyte surface may influence migration and maturation.     

Synthesis, stereochemistry and anticonvulsant action of 4-phenyltetrahydroisoquinolines

The racemic and optically active 4'- and 8-substituted tetrahydroisoquinolines 2-5 have been synthesized and their effect on the water-immersion stress ulcer in rats has been studied. All compounds prevent the formation of stress ulcer, the strongest effect being exhibited by compound 4 and its dextrarotatory isomer (R1 = Cl, R2 = NHCOOC2H5). The antiulcer activity of 4 is 30 to 50 times higher than that of the H2 receptor antagonists Cimetidin and Ranitidin used for comparison. The absolute configuration of the optically active compounds 2, 3 and 4 has been determined by means of chemical correlation. The antiulcer activity of 4 is characterized by enantioselectivity, S-(+)-4 is three times as active than R-(-)-4.