Extracorporeal membrane oxygenation following pediatric cardiac surgery: development and outcomes from a single-center experience.

Extracorporeal membrane oxygenation (ECMO) has emerged as an effective mechanical support following cardiac surgery with respiratory and cardiac failure. However, there are no clear indications for ECMO use after pediatric cardiac surgery. We retrospectively reviewed medical records of 76 pediatric patients [mean age, 10.8 months (0-86); mean weight, 5.16 kg (1.16-16.5)] with congenital heart disease who received ECMO following cardiac surgery between January 1997 and October 2010. Forty-five patients were treated with an aggressive ECMO approach (aggressive ECMO group, April 2005-October 2010) and 31 with a delayed ECMO approach (delayed ECMO group, January 1997-March 2005). Demographics, diagnosis, operative variables, ECMO indication, and duration of survivors and non-survivors were compared. Thirty-four patients (75.5%) were successfully weaned from ECMO in the aggressive ECMO group and 26 (57.7%) were discharged. Conversely, eight patients (25.8%) were successfully weaned from ECMO in the delayed ECMO group and two (6.5%) were discharged. Forty-five patients with shunted single ventricle physiology (aggressive: 29 patients, delayed: 16 patients) received ECMO, but only 15 (33.3%) survived and were discharged. The survival rate of the aggressive ECMO group was significantly better when compared with the delayed ECMO group (p<0.01). Also, ECMO duration was significantly shorter among the aggressive ECMO group survivors (96.5 ± 62.9 h, p<0.01). Thus, the aggressive ECMO approach is a superior strategy compared to the delayed ECMO approach in pediatric cardiac patients. The aggressive ECMO approach improved our outcomes of neonatal and pediatric ECMO.

Establishment and characterization of four myeloma cell lines which are responsive to interleukin-6 for their growth.

Four human myeloma cell lines (MM-S1, MM-A1, MM-Y1 and MM-C1) were established from patients in the terminal stage of multiple myeloma. All the cell lines were PCA-1 positive and three were CD38 (OKT10) positive. The class of cytoplasmic immunoglobulin in each of these cell lines was identical to that of the monoclonal protein detected in each patient. Epstein-Barr virus nuclear antigen was negative in all cell lines. An examination of the tritiated thymidine uptake showed that all four cell lines proliferated in response to interleukin-6 (IL-6), while MM-S1 also responded to IL-5. Immunological staining with an anti-IL-6 receptor monoclonal antibody revealed the presence of receptors for IL-6 on the cells from each cell line. Three of them formed colonies dependent on IL-6 in methylcellulose semi-solid culture. All four cell lines grew better when human plasma was added as a supplement to the culture in comparison to fetal calf serum. Northern blot analysis showed that the three cell lines tested did not express IL-6 messenger RNA. These results indicate that these four cell lines are responsive to IL-6, but not by an autocrine mechanism, at least in the three lines examined.

Experimental study of tracheal allotransplantation with cryopreserved grafts.

OBJECTIVE: Tracheal reconstruction is necessary in patients with extensive tracheal stenosis caused by neoplasm, trauma, and congenital disease. We investigated the possibility of tracheal allotransplantation with cryopreserved grafts in a canine model. METHODS: A seven-ring section of thoracic trachea was removed in 19 adult mongrel dogs. In group A (n = 4), a five-ring tracheal autograft was implanted. In group B (n = 6), a five-ring allograft was implanted without immunosuppression. In group C (n = 9), a five-ring cryopreserved tracheal allograft was implanted without immunosuppression. Omentopexy wrapping around the grafts and both anastomotic sites was used in all animals. RESULTS: All grafts survived without any evidence of atrophy or stenosis in group A. All animals in group B died of severe airway obstruction within 1 month, and postmortem examination of these grafts showed epithelial defect and necrotic tracheal cartilage in the scar tissue. In group C, no animals died of asphyxia caused by severe stenosis of the grafts. The graft epithelium was no longer present 20 days after transplantation, and the graft was covered with regenerated epithelium within about 60 days after the operation. CONCLUSION: These findings show that cryopreserved tracheal allografts can be transplanted by means of omentopexy without immunosuppression and that cryopreservation may reduce tracheal allogenicity.

In vitro growth pattern of myeloma cells in liquid suspension or semi-solid culture containing interleukin-6.

We examined in vitro growth pattern of myeloma cells from 21 patients with multiple myeloma either in liquid suspension or methylcellulose semi-solid culture, both in the presence of interleukin-6 (IL-6). The survival or growth of myeloma cells in liquid culture was classified into four categories. Type 1: myeloma cells survived for only 2-3 weeks in eight patients; Type 2: survival for 1-2 months in seven patients; Type 3: survival for more than 3 months without an obvious increase in cell number in three patients; and Type 4: continuous proliferation (cell line) in three patients. As the clinical stage advanced, the survival of myeloma cells became longer. All three myeloma cell lines were obtained from patients in an advanced clinical stage. Human plasma added to the liquid culture induced the survival or growth of myeloma cells better than fetal calf serum in any survival or growth type. Myeloma colonies or clusters were generated in seven of 21 patients, though myeloma colony formation was restricted to Type 4 patients. IL-6 neither prolonged the survival of myeloma cells nor promoted their growth in vitro except for Type 4 cells. Moreover, IL-6 did not increase the success rate of generating myeloma colonies in vitro. However, IL-6 did elevate the number of myeloma clusters in Types 1, 2 and 3 patients examined. These results suggest that IL-6 has a minor proliferative effect on myeloma cells in semi-solid culture but not in liquid suspension culture except for cells from patients with aggressive myeloma.

Effect of 1,25(OH)2D3 on normal human CFU-GM: target cells of the agent in the suppression of colony formation and induction of macrophage colonies.

1,25-Dihydroxyvitamin D-3 (1,25(OH)2D3) suppresses colony formation of normal human granulocyte macrophage progenitors (CFU-GM) and induces differentiation of colonies into monocyte macrophages in vitro. We examined whether or not the target cell of 1,25(OH)2D3 is only CFU-GM in the suppression and differentiation of colonies by the agent. Reduction of colony counts was observed only when 1,25(OH)2D3 was added to CFU-GM cultures at days 0 or 3, and after day 5 the agent did not affect the colony count. However, the delayed addition of 1,25(OH)2D3 elevated the proportion of granulocyte macrophage (GM) or macrophage (M) colonies even after 5 days of culture. We confirmed transformation of day 11 colony cells into macrophages by 1,25(OH)2D3 during the following 3 days' culture period based on serial observations of single colonies. Day 11 colonies contained very few CFU-GM and their most immature cells were promyelocytes. Short-term exposure to 1,25(OH)2D3 (4 h) of bone marrow cells, which had been precultured for 24 to 72 h with a purified granulocyte-colony stimulating factor caused a reduction of colony counts but did not elevate the proportions of GM or M colonies. These results indicate that 1,25(OH)2D3 inhibits the growth of CFU-GM itself and induces differentiation into macrophages at the progeny level (probably promyelocytes) and not at the level of CFU-GM.

Modifying a venovenous extracorporeal membrane oxygenation circuit to reduce recirculation.

Lung rest is the primary goal of venovenous extracorporeal membrane oxygenation for severe acute respiratory failure. To achieve this there has to be adequate extracorporeal flow. This can be achieved by a two-cannula technique in most cases. In some cases, extra flow is either not achievable or causes excessive recirculation. We report 8 patients in whom we achieved adequate blood and oxygen delivery using a three-cannula technique. Five patients survived (62.5%).

Partial liquid ventilation for acute allograft dysfunction after canine lung transplantation.

BACKGROUND: This study was designed to investigate the efficacy of partial liquid ventilation (PLV) on acute allograft dysfunction after lung transplantation. METHODS: The canine left lung allotransplantation model was used, with the graft preserved in 4 degrees C low-potassium dextran glucose solution for 18 hours. The control group (n = 6) had conventional mechanical ventilation, and the PLV group (n = 6) had perfluorooctylbromide instilled into the airway 30 minutes after reperfusion. For 360 minutes, allograft function and hemodynamics were evaluated. After the evaluation, myeloperoxidase activity of the graft tissue was assayed. RESULTS: All dogs survived for 360 minutes. In the PLV group, PaO2, shunt fraction, and alveolar to arterial gradient for O2 were significantly better than those in the control group after 120, 180, and 120 minutes, respectively (p < 0.05). After 240 minutes, peak airway pressure became significantly lower than that in the control group (p < 0.05). The PaO2 at 360 minutes was 102 +/- 55 mm Hg in the control group and 420 +/- 78 mm Hg in the PLV group (p < 0.0001), and the peak airway pressure was 21.4 +/- 4.1 mm Hg in the control group and 14.7 +/- 5.0 mm Hg in the PLV group (p < 0.05). Myeloperoxidase activity in the PLV group was lower than that in the control group. CONCLUSIONS: The study shows that PLV alleviated acute allograft dysfunction after lung transplantation.

Pilot investigation of hypothermia in neonates receiving extracorporeal membrane oxygenation.

BACKGROUND: Infants requiring extracorporeal membrane oxygenation (ECMO) support represent a high risk group in terms of cerebral injury. Mild hypothermia both during and after cerebral hypoxic ischaemia appears to be a promising strategy for offering neuroprotection. OBJECTIVE: To investigate whether mild hypothermia was both feasible and safe in infants receiving ECMO as a prelude to any formal assessment of this approach in a randomised trial. METHODS: Twenty infants (body weight less than 5 kg) with severe cardiopulmonary insufficiency, referred for ECMO support at Glenfield Hospital, Leicester, were enrolled in this study. Twenty consecutive infants (compromising four groups of five) were studied. Baseline data were obtained from a control group who were run throughout their course at 37 degrees C. The patients in the next group were managed with a core temperature of 36 degrees C for the first 12 hours of their ECMO run, before being warmed up to 37 degrees C. After successful completion, the next group of five were cared for at 35 degrees C for the first 12 hours, and, there having been no previous complications, the final group were cared for at 34 degrees C for the first 12 hours. Patients were assessed clinically and biologically. In addition to routine laboratory tests, cytokines (interleukin 6, interleukin 8, tumour necrosis factor alpha, and C reactive protein) were measured and coagulation tests (D-dimer, thrombin-antithrombin III complex, plasmin-alpha(2)-antiplasmin complex) were performed serially for five days. RESULTS: There were no significant differences among the four groups in gestational age, birth weight, age at the time of ECMO, Apgar scores at one and five minutes, pH before cannulation, oxygenation index, duration of ECMO, and survival rate to discharge from hospital. No adverse effects of mild hypothermia were found on patient management during ECMO. Laboratory data for up to five days of ECMO also showed no difference among the four groups. CONCLUSION: Mild hypothermia (34 degrees C) for the initial 12 hours of an ECMO run is feasible.

Effect of blood flow rate on thrombogenesis in a rabbit extracorporeal circulation model.

Blood flow is believed to affect the thrombogenicity of extracorporeal circulation (ECC). The purpose of this study was to look at the relationship between blood flow and thrombogenicity in a rabbit model of ECC. Rabbits were anesthetized and systematically heparinized. Bilateral jugular cannulation was performed, and the animals were placed on venovenous ECC. The circuits were composed of 1 m of 1/4 inch size surgical grade polyvinylchloride (PVC) tubing. ECC was maintained for 4 hours. Three experimental groups were studied: a high flow group (n=7; flow rate: 30 ml/min/Kg), low flow group (n=7; flow rate: 10 ml/mg/Kg), and no ECC group (n=7). Platelet count, fibrinogen concentration, PaO2/FiO2, and postmortem findings were evaluated. Platelet consumption was higher with high flow, and fibrinogen consumption was higher with low flow.

Experimental study on veno-venous extracorporeal membrane oxygenation for respiratory failure after lung transplantation.

Extracorporeal Membrane Oxygenation (ECMO) has been adopted as a means of strong respiratory support. In lung transplantation, reimplantation response is still a serious problem. It causes severe respiratory failure which is refractory to mechanical ventilation in some cases. The purpose of this study was to evaluate the effects of veno-venous ECMO after lung transplantation using a canine autotransplantation model. The autotransplantation model was created by keeping the left lung in a warm ischemic state for 2 h. After reperfusion, the right pulmonary artery was ligated. The following two groups were studied: Group 1, Control group, (no ECMO group) (n = 6). After reperfusion, both lungs were ventilated without ECMO. Group 2, ECMO group (n = 7). After reperfusion, veno-venous ECMO support was introduced with reduction of mechanical ventilation. In the no ECMO group, four of the animals died within 210 min after reperfusion. In the ECMO group, two of the animals died of severe pulmonary edema. Data of blood gas analyses (PaO2, PaCO2, and SvO2) after reperfusion were significantly better in the ECMO group, whereas there were no significant differences in both shunt fraction and pulmonary vascular resistance index. In this model with severe pulmonary edema induced by warm ischemia, veno-venous ECMO contributed to the improvement of hypoxemia and hypercapnia, but did not improve pulmonary hemodynamics.

Experimental study of partial liquid ventilation in the setting of acute respiratory failure induced by sea water lung lavage in rabbits.

To study the effect of partial liquid ventilation (PLV) with perfluorocarbon on acute respiratory failure, 3 groups of 17 rabbits were examined to compare. After acute respiratory failure was induced by lung lavage with sea water in 12 of the 17 rabbits, 7 of the 12 rabbits were treated with conventional mechanical ventilation (AC group) and 5 of the 12 rabbits were treated with PLV using perfluorocarbon (AP group). The remaining 5 normal rabbits without acute respiratory failure were treated with PLV with perfluorocarbon as a control group (PL group). In the PL group, PaO2, PaCO2, blood pH, pulmonary compliance or pathological findings were not so changed after PLV. In the AC and AP groups, PaCO2 significantly increased, and in contrast, PaO2 and pulmonary compliance significantly decreased after lung lavage. However, these findings improved to almost the same levels as those of a control group within 2 h after the PLV treatment in the AP group, but in the AC group, these gradually deteriorated over time. As for the pathological findings, pulmonary vascular congestion, alveolar hemorrhage and inflammatory infiltration were observed in the AC group. However, these findings were not observed in the specimens of the AP group. From these results, PLV with perfluorocarbon was shown to be useful to improve gas exchange and pulmonary functions without major side effects.

[Clinical evaluation of cepharanthin for chronic idiopathic thrombocytopenic purpura].

Twenty-two patients with steroid-unresponsive idiopathic thrombocytopenic purpura (ITP) were treated with cepharanthin, biscoclaurin alkaloid. Cepharanthin was administered orally at a daily dose of 40 mg. Continuous elevation of platelet counts of 6.6-15.0 x 10(4)/microliters and 3-5 x 10(4)/microliters was attained in five and two patients, respectively, 1 to 4 months after the administration. Treatment with cepharanthin might be worth attempting in refractory ITP.

[Complete remission induced by combined treatment with all-trans retinoic acid (ATRA) and granulocyte colony-stimulating factor (G-CSF) in a patient with relapsed acute promyelocytic leukemia].

In February, 1990, a 49-year-old man was admitted with petechia and gingival bleeding. The peripheral blood showed 5,200 leukocytes/microliters including 73% abnormal promyelocytes and 24,000/microliters platelets. Bone marrow puncture revealed that nucleated cell count was 331,250/microliters including 85.4% abnormal promyelocytes with 46XY, i(17q) chromosome. Coagulation tests revealed DIC. He was diagnosed as having acute promyelocytic leukemia, and he was treated with the BHAC-DMP protocol. He achieved complete remission, and received consolidation therapy and maintenance therapy. However, he relapsed in May, 1991 with 46XY, 16q-, i (17q) chromosome. He was treated with BHAC-MV protocol and again achieved complete remission. In June, 1992, he re-relapsed and 3.6% blasts and 10% abnormal promyelocytes was found in his bone marrow. He was treated for 14 days with 15 mg Aclarubicin without any change. Then he was treated with 60 mg All-trans retinoic acid (ATRA). After administration of ATRA, his peripheral blood leukocyte count increased temporarily but bone marrow suppression continued. Then he received continuous subcutaneous infusion of 24 micrograms/day granulocyte colony-stimulating factor (rhG-CSF). After treatment with ATRA and rhG-CSF, he entered a third complete remission.

[Clinical evaluation of traditional Chinese medicine for chronic idiopathic thrombocytopenic purpura].

The efficacy of traditional Chinese medicine (Kampo medicine) was examined in 40 patients with steroid-unresponsive idiopathic thrombocytopenic purpura (ITP). All patients were, at first, given Hochuekihi-to, and when they were refractory, therapy was switched to Sairei-to, Ninjinyoei-to, and Kamikihi-to. The efficacy rate was 20.0% by Hochuekihi-to, 20.7% by Sairei-to, 5.5% by Ninjinyoei-to and 6.7% by Kamikihi-to, respectively. Thus, overall responders were 12 in 40 patients with an effective rate of 30.0%. The mechanism of action of traditional Chinese medicine is discussed in relation to the production of various kinds of cytokines.

[Myelodysplastic syndromes in two young brothers].

Myelodysplastic syndromes that occurred in two young brothers are reported. A 19-year-old man was admitted to Kobe City General Hospital in May 1990 because of fever and nasal bleeding. On admission his hemoglobin was 5.5 g/dl, platelet count 1.5 x 10(4)/microliters and white cell count 1,700/microliters with 18% neutrophils and 80% lymphocytes. Bone marrow aspirate showed dysplastic features of trilineage blood cells with 4.8% myeloblasts. A diagnosis of refractory anemia was made. His younger brother, a 17-year-old man was examined in May 1990 because of increasing fatigability of 2 years' duration. His hemoglobin was 8.7 g/dl, platelet count 2.1 x 10(4)/microliters and white cell count 2,800/microliters. Bone marrow aspirate revealed morphological abnormalities in three lineages with 5.2% myeloblasts. He was diagnosed as having refractory anemia with excess of blasts. Their parent are consanguineous. The onset at a young age, reduced CD4 lymphocytes and similarity of dyshematopoietic findings suggests the presence of common genetic disorder in the pluripotent hematopoietic stem cells.

[Therapeutic effectiveness of vitamin D3 in patients with myelodysplastic syndromes, leukemias and myeloproliferative disorders].

We tried to treat 13 patients with myelodysplastic syndromes (MDS), leukemias and myeloproliferative disorders, with alfacalcidol for their hematological improvement. Eight of them had MDS, 2 acute leukemia (M3, M4), 1 chronic myelogenous leukemia and 2 primary myelofibrosis. All patients were untreated except for 3 patients (PASA, RAEB, AML-M4) who had been treated with mepitiostane, prednisolone and BH.AC-AMP regimen, respectively, prior to alfacalcidol therapy. All patients received alfacalcidol orally for at least one month. The dosage of alfacalcidol ranged from 0.25 to 10 micrograms/day, and the medicine was administrated intermittently when the dosage exceeded 6 micrograms/day to prevent hypercalcemia. The therapeutic effectiveness of alfacalcidol was evaluated according to a criteria by Koeffler (Cancer Treat Rep 69: 1399, 1985) with minor modifications. Three patients (PASA, RAEB, CMML) showed partial response, 3 (RAEB, RAEB in T, AML-M4) minor response and rest of the patients did not respond. The hematological improvement of 6 responders was transient (from 1 to 2 months), however, one patient (PASA) is still responding to alfacalcidol therapy (0.25 microgram/day) for over 12 months. The dysplastic features of hemopoietic cells in the bone marrow showed no noticeable change during the hematological improvement in these responders, suggesting the improvement was obtained as a result of alteration in the proliferation or differentiation of neoplastic clone. None of 13 patients developed hypercalcemia. One patient (AML-M4) became excitable on high dose alfacalcidol (10 micrograms/day). In conclusion, alfacalcidol therapy is effective in some patients with MDS or leukemias and appears worthy especially in the clinical state in which chemotherapy is not indicated.