Polycythemia Vera Diagnosed after Esophageal Variceal Rupture.

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm that leads to hyperviscosity and the risk of thrombosis. We encountered the case of a young male Filipino patient diagnosed with PV after the rupture of esophageal varices. The complete blood cell count showed a slight increase in white blood cells. An abdominal computed tomography scan disclosed splenomegaly and occlusion of the portal vein and collateral vessels. A blood examination demonstrated an increase in all three blood cell lines within three months. Based on the presence of severe hypercellularity of the bone marrow and positivity for the JAK2V617F mutation, we finally diagnosed the patient with PV.

Persistent endothelial damage after intravenous immunoglobulin therapy in Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology. Although endothelial cell damage associated with vasculitis might lead to the hypercoagulability that is involved in coronary artery disease, the changes in coagulation after intravenous immunoglobulin therapy (IVIG) have not been well investigated in KD. The aims of this study were to address the changes in coagulation before and after IVIG in KD, and to further elucidate the coagulation-inflammation axis, with special attention to endothelial damage. METHODS: We retrospectively collected the laboratory data before and after IVIG in 26 pediatric KD patients treated at the Nara Prefecture Western Medical Center between May 2010 and April 2012. Prothrombin time (PT), activated partial thromboplastin time (APTT) and levels of fibrin/fibrinogen degradation products (FDP) and D-dimer were assessed as coagulation markers. Fibrinogen, ferritin, serum amyloid A, procalcitonin and urine ß2 microglobulin were assessed as inflammation markers. Thrombomodulin, antithrombin, factor VIII activity (FVIII:C), and von Willebrand factor antigen (VWF:Ag) were used to assess endothelial damage. RESULTS: Prolonged PT and APTT before IVIG were significantly shortened after IVIG, and elevated levels of FDP and D-dimer were significantly decreased. Elevated levels of inflammation markers had decreased significantly after IVIG, but levels of FVIII:C and VWF:Ag remained high, even after IVIG. CONCLUSIONS: Ameliorated inflammation by IVIG might improve the hypercoagulable state. Nevertheless, our results suggest that endothelial damage might be prolonged in IVIG-treated patients. Control of endothelial damage in KD is critical.

[Case of drug-induced pneumonitis associated with a dietary supplement containing CoQ10].

A 61-year-old woman began to take a dietary supplement contained CoQ10 and perilla leaf extract. Two months later, a dry cough appeared. The number of eosinophils in peripheral blood was elevated and chest radiograph images showed infiltrative shadows in the left middle lung. A chest CT scan showed consolidation in the left upper lobe (S3) and lower lobe (S10). The percentage of eosinophils was abnormally high in bronchoalveolar lavage fluid (BALF), and examination of a transbronchial lung biopsy (TBLB) specimen showed marked infiltration of eosinophils in the alveolar wall. Drug lymphocyte stimulation test (DLST) indicated high stimulation index for both supplement containing CoQ10 and its element of CoQ10. We diagnosed drug-induced pneumonitis, caused by CoQ10. The symptoms of the patient and pulmonary infiltrative shadows on chest radiograph improved after she stopped taking the supplements and started taking prednisolone orally. Recently various dietary supplements are coming onto the market. Since the possible adverse effects of these supplements are not investigated extensively, care should be taken for symptoms relating to food supplements.

Protective effects of a selective neutrophil elastase inhibitor (sivelestat) on lipopolysaccharide-induced acute dysfunction of the pulmonary microcirculation.

OBJECTIVE: The purpose of this study was to evaluate the effect of a neutrophil elastase inhibitor, sivelestat, on lipopolysaccharide-induced acute lung injury through analysis of hemodynamic changes in the pulmonary microcirculation. DESIGN: Randomized animal study. SETTING: Medical school laboratory. SUBJECTS: Twenty-seven Wistar rats (15 rats for microspectroscopic observations, 12 rats for measurements of neutrophil elastase activity and wet-to-dry ratio). INTERVENTIONS: Thoracosternotomy was performed on male Wistar rats under continuous anesthesia and mechanical ventilation. Rats were divided into three groups (n = 5 each groups) on the basis of the reagent used: lipopolysaccharide group (100 microg/kg lipopolysaccharide intravenously), sivelestat group (10 mg/kg sivelestat; 100 microg/kg lipopolysaccharide intravenously), and control group (saline only, intravenously). MEASUREMENTS AND MAIN RESULTS: We measured morphologic changes and hemodynamic variables, including tissue blood flow, erythrocyte velocity, erythrocyte count, thickness of interalveolar septa, and leukocyte adhesion in the pulmonary microcirculation, with a video-rate (33 msec/frame) dual-spot microspectroscopy system (DSMSS) and a laser-Doppler flowmeter. Blood-free wet-to-dry ratio and neutrophil elastase activity in bronchoalveolar lavage fluid, serum, and supernatant of lung homogenate were measured in another set of experiments (n = 4 for each group). Sixty minutes after lipopolysaccharide administration, severe thickening of the interalveolar septa was observed in the lipopolysaccharide but not the sivelestat group. In the lipopolysaccharide group, DSMSS measurements of erythrocyte velocity and hemoglobin oxygenation in single capillaries were decreased significantly (vs. control p < .05, vs. sivelestat p < .01), whereas tissue blood flow and erythrocyte velocity measurements from laser-Doppler flowmeter were increased significantly (vs. control p < .05, vs. sivelestat p < .01). The number of adherent leukocytes was increased significantly in the lipopolysaccharide group at 30, 45, and 60 mins after lipopolysaccharide administration (vs. control p < .01, vs. sivelestat p < .05). The number of adherent leukocytes did not increase in the sivelestat group. The wet-to-dry ratio was significantly higher in the lipopolysaccharide group than in control (p < .05) and sivelestat (p < .05) groups. Neutrophil elastase activities in the bronchoalveolar lavage fluid, serum, and lung tissue were all significantly lower in the sivelestat group than in the lipopolysaccharide group (p < .05). CONCLUSIONS: Lipopolysaccharide induces leukocyte adhesion in the pulmonary microcirculation, resulting in decreased tissue hemoglobin oxygen and alveolar and interstitial edema. The selective neutrophil elastase inhibitor sivelestat reduces neutrophil elastase activity and attenuates acute changes in the pulmonary microcirculation.

Serial changes in leukocyte deformability and whole blood rheology in patients with sepsis or trauma.

BACKGROUND: The objective of this study was to investigate serial changes in leukocyte deformability and rheologic properties of whole blood in patients with sepsis or trauma. METHODS: Seventeen sepsis patients and 22 trauma patients were enrolled. Leukocyte deformability and rheologic properties of whole blood were determined with the use of a microchannel array etched on a single-crystal silicon tip, simulating the microvasculature. The number of obstructed microchannels (NOM) was used as a measure of leukocyte deformability. Transit time (TT), i.e., the time taken for 100 microL of whole blood to pass through the microchannel array was also used as rheologic measure. Oxidative activity and F-actin content of neutrophils was measured in patients with sepsis. RESULTS: NOM and TT significantly increased in patients when sepsis was diagnosed. In survivors, NOM and TT decreased at the time of recovery from sepsis, but in non-survivors values remained high. Oxidative activity and F-actin content of neutrophils increased significantly as leukocyte deformability decreased. In patients with severe trauma, NOM and TT increased after injury and decreased by the time of recovery from the critical stage. CONCLUSION: We conclude that leukocyte deformability decreases in patients with sepsis or severe trauma and that this change negatively affects rheologic properties of whole blood.

Dopamine does not correct oxygen consumption/oxygen delivery relation abnormality during vasomotor shock induced by interleukin-1beta.

We previously showed that interleukin 1beta (IL-1beta) induces vasomotor shock and impairs the oxygen consumption (VO2)/oxygen delivery (DO2) relation by increasing the slope of the supply-independent line in rabbits. In the present study, we investigated the inotropic effect of dopamine on the VO2/DO2 abnormality induced by IL-1beta. Twelve rabbits were divided into two groups (n = 6, each) and were given 10 microg/kg of IL-1beta or saline (control) intravenously. After baseline measurements were obtained, dopamine was infused continuously at a rate of 20 microg/kg/min throughout the study in both groups. All rabbits were subjected to stepwise cardiac tamponade to reduce the DO2 to <5 mL/min/kg by inflation of a handmade balloon placed into the pericardial sac. The VO2/DO2 relation was then analyzed by the dual-line method. Dopamine failed to correct the IL-1beta-induced decrease in mean arterial pressure to the baseline level. Dopamine significantly increased cardiac index in both groups, resulting in significant increases in DO2 (IL-1beta, 28.5 +/- 6.0 mL/min/kg from baseline 24.1 +/- 3.5 mL/min/kg; control, 27.7 +/- 2.9 mL/min/kg from baseline 22.9 +/- 2.9 mL/min/kg), but did not affect VO2 (IL-1beta, 10.0 +/- 0.5 mL/min/kg from baseline 9.9 +/- 0.7 mL/min/kg; control, 10.2 +/- 0.4 mL/min/kg from baseline 10.2 +/- 0.2 mL/min/kg). The IL-1beta group showed a significantly greater supply-independent line slope than that of controls (IL-1beta, y = 0.14x + 6.3; control, y = 0.06x + 8.6) during stepwise decreases in DO2. These results indicate that continuous infusion of dopamine at 20 microg/kg/min increases DO2 but does not correct the vasomotor disturbance or VO2/DO2 abnormality caused by IL-1beta.

Long-term enhanced expression of heat shock proteins and decelerated apoptosis in polymorphonuclear leukocytes from major burn patients.

Heat shock proteins (HSPs), as molecular chaperones, have been reported to protect cells against a variety of environmental stresses. The objective of this study was to clarify the serial changes in expression of HSPs, oxidative activity, and apoptosis in polymorphonuclear leukocytes (PMNLs) from burn patients. Eight patients with severe burns (mean burn index 24.0 +/- 6.1) were included. Blood samples were serially obtained at five time points: days 0 to 1, days 2 to 7, days 8 to 14, days 15 to 21, and days 22 to 28. We measured expressions of HSP27, HSP60, HSP70, and HSP90 in permeabilized PMNLs by flow cytometry with the use of a monoclonal antibody against each HSP. The oxidative activity and apoptosis in PMNLs were also measured by flow cytometry. During all five time periods, expressions of HSP27, HSP60, and HSP70 in PMNLs from burn patients were significantly greater than those in PMNLs from healthy volunteers. The expression of HSP90 in PMNLs of burn patients increased between days 2 and 21. Oxidative activity in their PMNLs was significantly enhanced between days 2 and 28, and PMNL apoptosis was markedly inhibited for as long as 4 weeks after thermal injury. In conclusion, major burn causes long-term, enhanced expression of HSPs in PMNLs along with increased oxidative activity and decelerated apoptosis. The enhanced expression of HSPs may regulate the oxidative stress response and life-span of PMNLs in burn patients.

Physiologic responses to small emboli and hemodynamic effects of changes in deformability of polymorphonuclear leukocytes in isolated rabbit lung.

We hypothesized that polymorphonuclear leukocytes (PMNs) exposed to lipopolysaccharide (LPS) or chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) would alter the pulmonary hemodynamics of buffer-perfused rabbit lung. Pulmonary arterial pressure (Ppa) was measured at baseline, at peak response, and at 30 min after PMN infusion in the perfusate (Ppa x time, PT product). Infusion of peritoneal-harvested PMNs resulted in a transient increase in both pulmonary vascular resistance (PVR) and lung weight. PVR also increased when glutaraldehyde-treated rabbit PMNs (GPMNs) or beads were infused. Upstream PVR (Pao-Pdo) remained high with the infusion of GPMNs and beads and returned to baseline only when PMNs were infused 30 min thereafter. FMLP-exposed PMNs increased the peak Ppa and PT product. Pretreatment with 3-isobutyl-1-methylxanthine (IBMX) blocked this increase in pressure, suggesting the release of vasoconstrictor(s) or a direct effect of FMLP. PMNs exposed to LPS increased peak Ppa and PT product with and without the addition of IBMX. Cytochalasin D treatment of PMNs prevented the increase in PT product, suggesting that actin polymerization of PMNs is involved. The effects of these agents on PMN rigidity were verified by means of 6.5-microm polycarbonate filters. PMN suspension treated with FMLP or LPS increased filter perfusion pressure and PT product. Cytochalasin D prevented these increases. These results suggest that, initially after injection, PMNs behave like small beads embolizing primarily the small arteries in the lung and that they then move distally through the vasculature. Exposure to FMLP or LPS alters PMN deformability and the ability of PMNs to pass through the pulmonary vasculature, resulting in increased pulmonary vascular resistance.