Coronary artery fistula presenting as bacterial endocarditis

Coronary artery fistula is often considered to be a benign and rare congenital anomaly. It is usually an incidental finding encountered during routine cardiac catheterization. We report a case of a patient presenting with endocarditis involving a large coronary artery fistula connecting an aneurysmal circumflex coronary artery to the coronary sinus. The diagnosis was initially made by echocardiography and confirmed by cardiac catheterization. In addition, we briefly discuss the literature on management of this coronary anomaly.     

Initiation of the extrinsic pathway of coagulation by human and rabbit alveolar macrophages: a kinetic study

We examined assembly and expression of the factor X activating complex on human and rabbit alveolar macrophages. Kinetic parameters of the factor X activating reaction were determined by functional titrations of factors VII and X with macrophage tissue factor (TF) added. We found rapid activation of factor X to Xa on alveolar macrophage surfaces. Detection of rapid factor Xa formation on macrophages required addition of exogenous factors VII and X. At plasma concentrations of the purified factors, factor Xa was formed on freshly isolated macrophages at approximately 5.4 pmol/min/10(6) cells. After macrophage maturation in culture for 20 hours with LPS (endotoxin) added, the factor X activation rate was increased two- to sixfold. The km' (apparent km) of TF-factor VII enzymatic complexes assembled on alveolar macrophages for factor X were (258 +/- 55 and 475 +/- 264 nmol/L for human and rabbit cells, respectively). The km' did not change during macrophage maturation in culture, but V'max (apparent Vmax) was consistently increased. The K1/2 of human factor VII (concentrations giving half maximal rates of factor X activation) for the interaction with human and rabbit alveolar macrophage TF were 0.191 +/- 0.096 and 1.7 +/- 0.7 etamol/L, respectively. The K1/2 were not significantly changed after maturation, whereas rates of Xa formation at saturation with factor VII were increased. The fast rates of factor X activation observed at physiologic concentrations of plasma-derived factors VII and X indicate that TF on alveolar macrophages is likely to provide sites for binding of factor VII and activation of factor X in vivo during clotting reactions associated with alveolar edema and inflammation.     

Nasal dermoids: the significance of a midline punctum

Nasal dermoids are rare and their diagnosis is often delayed until complications occur. Signs such as a midline nasal punctum may be noted at birth but the significance of this finding frequently passes unrecognised. The cases are reported of two patients which illustrate the typical presentation of these lesions and their subsequent management is discussed.     

Induction of cytokine tolerance requires internalization of Chylomicron-Bound LPS into hepatocytes

BACKGROUND: Chylomicron-bound LPS (CM-LPS) renders hepatocytes unresponsive to stimulation by proinflammatory cytokines, a process termed cytokine tolerance. We have shown that cytokine tolerance is a time- and dose-dependent process requiring functional low-density lipoprotein receptors (LDLR). Thus, we hypothesized that cytokine tolerance directly correlates with the internalization of CM-LPS complexes, and inhibition of lipoprotein binding and/or internalization inhibits the induction of cytokine tolerance in hepatocytes. MATERIALS AND METHODS: We correlated the rate of internalization of radioiodinated CM-LPS complexes with hepatocellular NO production as a measure of cytokine responsiveness. In additional studies, we used four different strategies to inhibit binding/internalization of CM-LPS via LDLR and then determined the effect of each strategy on the induction of cytokine tolerance. RESULTS: There was a strong inverse correlation between the internalization of CM-LPS and the responsiveness of hepatocytes to proinflammatory cytokines (r(2) = -0.997). Furthermore, the greater the degree of LDLR inhibition, the less susceptible hepatocytes were to the induction of cytokine tolerance by CM-bound LPS. Accordingly, cytokine tolerance induction was inhibited in hepatocytes with decreased membrane expression of LDLR as compared to control cells (69 versus 12% control; P = 0.005). Competitive inhibition of CM-LPS binding prevented internalization of CM-LPS and resulted in loss of the cytokine-tolerant phenotype. Whereas CM-LPS successfully induced cytokine tolerance in ldlr(-/-) hepatocytes, it only occurred after a prolonged pretreatment period of 8 h. CM-LPS complexes containing apolipoprotein (apo) E(2) also required a prolonged pretreatment period to induce a level of cytokine tolerance comparable to that induced by CM-LPS complexes containing either apo E(3) or E(4). CONCLUSION: Lipoprotein-bound LPS inhibits the responsiveness of hepatocytes to proinflammatory cytokines in a manner directly correlated with the internalization of LPS. Furthermore, inhibition of lipoprotein binding/internalization prevents this LPS-mediated induction of cytokine tolerance in rodent hepatocytes.     

Subcellular Phototoxicity of Photofrin-II and Lutetium Texaphyrin in Cells In Vitro

. Three cell types including bovine pulmonary artery endothelium cells (CPAE), rat kangaroo kidney cells (PTK₂), and human larynx epidermoid carcinoma cells (Hep-2) were used to study subcellular localisation and phototoxicity of Photofrin-II and lutetium texaphyrin (Lu Tex). Cells were examined for fluorescence after administration of the photosensitisers. Subcellular regions were exposed with a laser microbeam system that used an argon ion laser pumped dye laser generating a 630 nm for Photofrin-II and 730 nm for Lu Tex. Fluorescence detection suggests that the Photofrin-II is bound primarily to the mitochondria with some diffuse fluorescence in the rest of the cytoplasm. The fluorescence in Lu Tex treated cells appears to be localised to the lysosomes. The percentage of damaged cells following light exposure to the different subcellular regions after Photofrin-II or Lu Tex treatment demonstrates that the nuclear region was the most sensitive target followed by the perinuclear region and peripheral cytoplasm region. Paper received 27 January 1998; accepted after revision 21 August 1998.     

COLD PRESSOR TEST DEMONSTRATES RESIDUAL SYMPATHETIC CARDIOVASCULAR ACTIVATION IN FAMILIAL DYSAUTONOMIA

Objectives: Patients with polyneuropathy and antibodies to myelin-associated glycoprotein (MAG) and sulphated glucuronyl paragloboside (SGPG) differ from chronic inflammatory demyelinating polyneuropathy (CIDP) because of a slower, progressive course, symmetrical and predominantly sensory involvement of legs, predominantly distal slowing of motor conductions, and poorer response to therapy. We studied whether a wide set of electrophysiologic parameters may differentiate these two neuropathies. Methods: We reviewed the electrophysiological studies of 10 patients with anti-MAG/SGPG antibodies and 22 with CIDP examining: (1) motor conduction velocity and distal compound muscle action potential amplitude; (2) conduction block (CB) and temporal dispersion; (3) distal motor latency and terminal latency index (TLI); (4) F wave and proximal conduction time; and (5) sensory conduction and occurrence of abnormal median with normal sural sensory potential. Results: Anti-MAG/SGPG neuropathies showed: (1) more severe involvement of peroneal nerves; (2) more frequent disproportionate distal slowing of motor conductions (TLI less than or equal to 0.25) and absent sural potential; and (3) no CB. However 3/22 CIDP patients also had at least two nerves with TLI 0.25 and no CB. Conclusions: Electrophysiologic findings suggest in anti-MAG/SGPG neuropathy a length-dependent process with a likely centripetal evolution. A disproportionate slowing of conduction in distal segments of motor nerves suggests the diagnosis of anti-MAG/SGPG neuropathy, although it is not pathognomonic.     

Treatment of normal individuals with granulocyte-colony-stimulating factor: donor experiences and the effects on peripheral blood CD34+ cell counts and on the collection of peripheral blood stem cells

BACKGROUND: Granulocyte-colony-stimulating factor (G-CSF) has been used in patients to increase the level of circulating hematopoietic progenitors. Although G-CSF has been administered to some healthy individuals, the kinetics of mobilization of peripheral blood stem cells (PBSCs), the optimum dose schedule and the incidence and nature of adverse reactions in normal individuals are not completely defined. STUDY DESIGN AND METHODS: Normal individuals (n = 102) who received G- CSF for 5 or 10 days at doses of 2, 5, 7.5, or 10 micrograms per kg per day were studied. The subjects were observed for symptoms and physical changes, and blood samples were obtained for a variety of laboratory tests. After 5 or 10 days of G-CSF treatment, PBSCs were collected by apheresis and analyzed. RESULTS: Overall, 89 percent of the individuals completed the 5-day treatment protocol and 88 percent completed the 10- day protocol without modification of the dose of G-CSF administered. Ninety percent of donors experienced some side effect of G-CSF. The most frequent effects noted were bone pain (83%), headache (39%), body aches (23%), fatigue (14%), and nausea and/or vomiting (12%). The dose of G-CSF administered directly affected the proportion of people with bone pain (p = 0.025) or body aches (p = 0.045) or who were feeling hot or having night sweats (p = 0.02) or taking analgesics (p = 0.01). With the 5-day dose schedule, several changes in serum chemistries occurred, including increases in alkaline phosphatase (p = 0.001), alanine aminotransferase (p = 0.0013), lactate dehydrogenase (p = 0.0001), and sodium (p = 0.0001). Decreases occurred in glucose (p = 0.045), potassium (p = 0.0004), bilirubin (p = 0.001), and blood urea nitrogen (p = 0.0017). In donors who received G-CSF for 5 days, the absolute neutrophil count was increased after one G-CSF dose, and it reached a maximum on Day 6, as did the number of CD34+ cells (64.6 +/? 55.9 × 10(6) cells/L). In those same donors, the platelet count after apheresis on Day 6 was 32 +/? 13 percent lower than pretreatment values (250 +/? 42 × 10(9) cells/L). In donors receiving G-CSF for 10 days, the neutrophil count reached a maximum on Day 8, but the number of CD34+ cells peaked on Day 6 (58.3 +/? 52.1 × 10(5) cells/L) and then declined. The platelet count decreased from pretreatment values by 28 +/? 12 percent prior to apheresis on Day 11. When individuals were treated for 5 days with G-CSF, the quantity of CD34+ cells collected was directly related to the G-CSF dose. When 5 micrograms per kg per day was given, 2.80 +/? 1.81 × 10(8) cells were collected, compared with collection of 4.67 +/? 3.11 × 10(8) cells when 10 micrograms per kg per day was given (p = 0.04). More important, PBSCs collected after 10 days of G-CSF administration (5 micrograms/kg/day) had significantly fewer CD34+ cells (0.82 +/? 0.37 × 10(8) cells, p = 0.01) than did PBSCs collected after 5 days of G-CSF (5 micrograms/kg/day). CONCLUSION: Most normal donors receiving G-CSF experience side effects, but these are mild to moderate in degree. Some alterations in blood chemistries occur, but none were clinically serious. Because of the symptoms associated with G-CSF, these individuals must be monitored closely. The treatment of normal donors with G-CSF for more than 5 days significantly decreased the number of circulating CD34+ cells and the quantity collected by apheresis.