[Osmotic pressure].
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Biomedical subjects
Publications and source records attributed to M Endo.
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BACKGROUND: The limited exposure typical of new minimally invasive surgical approaches to cardiac surgery makes it difficult to utilize traditional equipment such as temporary pacing electrodes or the placement of drainage tubes into the lateral pleural space. To overcome these difficulties, we have developed specialized drainage tubes just for limited access cardiac surgery. METHODS: The first device is a drainage tube with temporary pacing function. It has three fixed electrodes and one free pacing wire incorporated into an elliptical, angled 28 Fr silicone drainage tube. This tube is placed in the space between the heart and the diaphragm. The two fixed electrodes provide epicardial contact for ventricular pacing. The third fixed electrode and one free pacing wire are for the purpose of atrial pacing (Japanese patent #2,701,135). The second device is a Y-shaped drainage tube. Frequently, the pleural space is opened during harvesting of an internal mammary graft and then insertion of a chest tube in the thoracic cavity becomes necessary. We developed a new Y-shaped tube where one segment is placed in the retrosternal space and one segment is placed in the pleural cavity. (Japanese Association of Intellectual Copyright #130,591) RESULTS: The drainage-pacing device was used in 48 coronary artery bypass grafting (CABG) patients. Drainage function and pacing function were excellent in all patients. The bifurcated drainage device was used in 34 patients achieving effective drainage of both cavities without complication during or after removal. CONCLUSIONS: Due to the limited surgical exposure provided by the newer minimally invasive procedures in cardiac surgery, specialized equipment that can be inserted through small incisions needs to be developed. We report the development of a new drainage-pacing device as well as a bifurcated drain for simultaneous drainage of the mediastinal and pleural cavities. These devices have facilitated minimally invasive cases and were free of complications.
The RGL protein, a homolog of the Ral GDP dissociation stimulator (RalGDS), has been identified as a downstream effector of Ras. In the present study, the solution structure of the Ras-binding domain of RGL (RGL-RBD) was determined by NMR spectroscopy. The overall fold of RGL-RBD consists of a five-stranded beta-sheet and two alpha-helices, which is the same topology as that of RalGDS-RBD. The backbone chemical shift perturbation of RGL-RBD upon interaction with the GTP analog-bound Ras was also examined. The solution structure of RGL-RBD, especially around some of the Ras-interacting residues, is appreciably different from that of RalGDS-RBD.
In this prospective trial, a total of 74 children who were scheduled to undergo high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) were prospectively randomized at diagnosis to evaluate the effectiveness of exogenous granulocyte colony-stimulating factor (G-CSF) treatment in accelerating hematopoietic recovery after PBSCT. The diagnosis included acute lymphoblastic leukemia (ALL) (n = 27), neuroblastoma (n = 29), and miscellaneous solid tumors (n = 18). Eligibility criteria included (1) primary PBSCT, (2) chemotherapy-responsive disease, and (3) collected cell number >1 x 10(5) colony-forming unit-granulocyte-macrophage (CFU-GM)/kg and >1 x 10(6) CD34(+) cells/kg patient's body weight. After applying the above criteria, 11 patients were excluded due to disease progression before PBSCT (n = 6) or a low number of harvested cells (n = 5), leaving 63 patients for analysis; 32 patients in the treatment group (300 microg/m2 of G-CSF intravenously over 1 hour from day 1 of PBSCT) and 31 in the control group without treatment. Two distinct disease-oriented high-dose regimens without total body irradiation consisted of the MCVAC regimen using ranimustine (MCNU, 450 mg/m2), cytosine arabinoside (16 g/m2), etoposide (1.6 g/m2), and cyclophosphamide (100 mg/kg) for patients with ALL, and the Hi-MEC regimen using melphalan (180 mg/m2), etoposide (1.6 g/m2), and carboplatinum (1.6 g/m2) for those with solid tumors. Five patients (two in the treatment group and three in the control group) were subsequently removed due to protocol violations. All patients survived PBSCT. The median numbers of transfused mononuclear cells (MNC), CD34(+) cells, and CFU-GM were, respectively, 4.5 (range, 1 to 19) x 10(8)/kg, 8.0 (1.1 to 25) x 10(6)/kg, and 3.7 (1.2 to 23) x 10(5)/kg in the treatment group (n = 30) and 2.9 (0.8 to 21) x 10(8)/kg, 6.3 (1.1 to 34) x 10(6)/kg, and 5.5 (1.3 to 37) x 10(5)/kg, respectively, in the control group (n = 28), with no significant difference. After PBSCT, the time to achieve an absolute neutrophil count (ANC) of >0.5 x 10(9)/L in the treatment group was less than that in the control group (median, 11 v 12 days; the log-rank test, P =.046), although the last day of red blood cell (RBC) transfusion (day 11 v day 10) and the duration of febrile days (>38 degrees C) after PBSCT (4 v 4 days) were identical in both groups. However, platelet recovery to >20 x 10(9)/L was significantly longer in treatment group than control group (26 v 16 days; P =.009) and >50 x 10(9)/L tended to take longer in the treatment group (29 v 26 days; P =.126), with significantly more platelet transfusion-dependent days (27 v 13 days; t-test, P =.037). When patients were divided into two different disease cohorts, ALL patients showed no difference in engraftment kinetics between the G-CSF treatment and control groups, while differences were seen in those with solid tumors. We concluded that the marginal clinical benefit of 1 day earlier recovery of granulocytes could be offset by the delayed recovery of platelets. We recommend that the routine application of costly G-CSF therapy in children undergoing PBSCT should be seriously reconsidered.
This was a phase I, multi-center study of 13 pediatric patients (median age, 11 years) to evaluate toxicity, hematopoietic recovery, and graft-versus-host disease (GVHD) after allogeneic transplantation of enriched blood CD34(+) cells obtained from genotypically haploidentical but partially HLA-mismatched related donors (8 parents and 5 siblings). With regard to rejection, donor HLA disparity was 1 (5), 2 (6), or 3 loci (2). With regard to GVHD, recipient HLA disparity was 0 (1), 1 (3), 2 (8), or 3 (1). The patients suffered from acute myelogenous leukemia (6), chronic myelogenous leukemia (4), acute lymphoblastic leukemia (2), or hemolytic anemia plus immunodeficiency disorder (1). To reduce the risk of graft failure through the infusion of a large amount of stem cells, peripheral blood cells (PBC) were mobilized by recombinant granulocyte colony-stimulating factor (G-CSF; lenograstim, 10 microgram/kg/d for 5 days) and collected by 2 to 5 aphereses. To both enhance engraftment and reduce GVHD, CD34(+) cells were enriched using immunomagnetic procedures with the Baxter ISOLEX 300 system (Baxter Healthcare Corp, Irvine, CA) and cryopreserved. After variable cytoreductive regimens, a median of 7.7 (range, 2.2 to 14) x 10(6)/kg of CD34(+) cells and 1.03 (0.05 to 2.09) x 10(5)/kg CD3(+) cells were infused. Using Center-specific posttransplant supportive care and immunosuppressive GVHD prophylaxis, two patients experienced early death; one from veno-occlusive disease at day 17 and one from sepsis at day 18. Nine of 11 patients showed signs of engraftment; however, subsequent rejection was seen in 4 patients, 2 of whom had autologous recovery. Eight patients were evaluated in the early phase of marrow recovery. The median number of days to achieve an absolute granulocyte count of 0.5 x 10(9)/L was 14 (range, 9 to 20) and that to achieve a platelet count of 20 x 10(9)/L was 17.5 (range, 12 to 23). Donor chimerism persisted in five patients until death or current survival. All of the surviving patients with functioning-donor-type hematopoiesis were given total body irradiation. De novo acute GVHD (grades II and IV) was observed in two of the eight evaluated patients. Scheduled donor lymphocyte infusion (DLI), using the CD34(-) fraction, was administered to four patients, free of de novo acute GVHD, beginning between 28 to 43 days after transplant. Three of these patients developed acute GVHD (grades I, II, and IV). Cytomegalovirus infection was a major infectious complication but was successfully managed with gamma-globulin and gancyclovir treatment with or without additional DLI. Five patients are currently surviving, free of disease, with a follow-up ranging from 476 to 937 days. Each survivor has functioning hematopoiesis, three of donor origin and two of autologous origin. In conclusion, our results show that enriched blood CD34(+) cells from a mismatched haploidentical donor are a feasible alternative source of stem cells, but do not appear to ensure engraftment. Because none of the patients who were administered DLI survived, the therapeutic efficacy and safety of periodic DLI, as an integrated part of such transplants, needs to be clarified in further studies.
The antitumor activity of a novel 4'-thionucleoside, 1-(2-deoxy-2-fluoro-4-thio-beta-D-arabinofuranosyl)cytosine (4'-thio-FAC), was evaluated. 4'-Thio-FAC inhibited the in vitro growth of various human cancer cell lines, particularly the growth of cell lines established from gastric and colorectal carcinomas, while its oxy-type congener 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)cytosine (FAC) showed little or no activity against such solid cancer cell lines. 4'-Thio-FAC showed a remarkable antitumor effect against human tumors subcutaneously implanted into nude mice and was highly effective even by oral administration. 4'-Thio-FAC was less susceptible to deamination by cytidine deaminase than FAC and 2'-deoxy-2',2'-difluorocytidine (gemcitabine) and therefore is a promising drug candidate for cancer chemotherapy.
A synchrotron light source dedicated to medical applications is required to be compact for installation in limited spaces at hospitals. The NIRS storage ring, with a circumference of 44.8 m, is designed to accelerate electrons up to 1.8 GeV and to store a beam of 400 mA. The ring is composed of superconducting bending magnets for downsizing. A beam of 300 MeV is injected into the ring from a microtron operated at an L-band RF frequency. There are two superconducting multipole wigglers with nine poles and a maximum field of 8 T, which can produce a photon flux of about 1.4 x 10(13) photons s(-1) mrad(-1) (0.1% bandwidth)(-1) at 33 keV used for coronary angiography.
Although perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) are associated with vasculitic neuropathy, their association with central nervous system (CNS) disorders has not been studied except for one report on optic-spinal type of multiple sclerosis associated with serum pANCA. We examined pANCA in sera from 98 patients with various CNS disorders, such as 58 MS, 17 myelitis, 12 HTLV-1 associated myelopathy, and 11 other CNS diseases using indirect immunofluorescence methods. The results showed serum pANCA to be positive in five patients with a peculiar type of myelitis, including two with MS and three with etiology unknown myelitis. All of these ANCA-positive patients were women and had acute or subacute myelopathy with various severities. MRI revealed segmental swelling of the spinal cord with T2 hyperintensity in the acute stage of the disease. Marked pleocytosis (227.8+/-101/mm3) and elevated protein level (128.8+/-52 mg/dl) in CSF were noted. Four of the patients had anti-nuclear antibodies and two had previous histories of symptoms suggesting autoimmune disorders. In a search for target antigens of pANCA, myeloperoxidase reactivity was found in the sera from two myelitis patients. Clinical and laboratory features of myelitis patients with pANCA in the present study are different from those of typical MS patients. Further study will be needed to delineate the role of pANCA in the pathogenesis of a specific type of myelitis.
The Smad3 gene is a member of the Smad family, vertebrate homologues of Drosophila Mad, and its gene product is a cytoplasmic element in the TGF-beta signaling pathway. Smad2 and Smad4/DPC4, other members of the Smad family, are possibly tumor suppressor genes because alterations of these genes occurred in various carcinomas. We determined the genomic structure of human Smad3 which consists of nine exons. Then we examined whether or not Smad3 gene mutations exist in sporadic and hereditary non-polyposis colorectal cancers and found no mutations in the entire coding region in 50 cancers. Loss of heterozygosity of Smad3 was observed in two of the 17 (11.8%) informative cases using a polymorphism found in intron 2. These findings suggest that the Smad3 gene may not play an important role in the tumorigenesis of colorectal cancers.
To investigate the more effective route of oral administration of glycerol to decrease the raised ICP, two different routes were employed in the clinical practice. The one was through a Naso-Gastric tube, and the other was through an Entero-Duodenal tube. Pharmacokinetics of glycerol in relation to the decrease of ICP, and the changes of other parameters which could influence the serum osmotic pressure were sequentially monitored for initial 30 minutes. In the group of Entero-Duodenal route, the time to reach to the maximum glycerol concentration (Tmax) was faster, the maximum concentration of glycerol (Cmas) was higher, and ICP reduction rate was greater than these in the group of Naso-Gastric route. Other parameters (Na, K, BUN and Glucose) showed no significant difference between the two routes. It can be concluded that the Entero-Duodenal administration of glycerol is the more effective route to decrease the raised ICP, when it is administered orally.
Due to recent advances in endoscopic surgical techniques, it has now become possible to perform endoscopic resection of most early invasive carcinomas of the colon and rectum (EIC) even if the lesions have invaded the submucosa. In the present study, we investigated the microscopic characteristics of superficial EIC compared with protruding-type EIC, focusing particular attention on histological type, the presence or absence of vascular invasion, the extent of submucosal invasion, and other adverse prognostic factors, to establish appropriate treatment strategies. Our findings led us to conclude that: (1) most cases of EIC can be cured by endoscopic resection if their gross aspects are classified as type IIc, superficial depressed, or type IIa, superficial elevated; (2) colorectal resection with lymph node dissection should be performed first for type IIa + IIc EIC because these lesions are apt to be associated with a large number of adverse prognostic factors; (3) subsequent colorectal resection should be performed after initial endoscopic treatment of EIC if there are adverse prognostic indicators of metastasis in the endoscopically resected specimen, such as moderately or poorly differentiated adenocarcinoma, lymphatic invasion, venous invasion, or extensive submucosal invasion.
We performed surgical treatment in a case of löffler's endocarditis. The patient was a 32-year-old male whose first symptom was easy fatigability. Blood count showed eosinophilia (eosinocyte count 6720/mm3). Echocardiography and vetriculography showed thickened bilateral endocardium and extension disturbance. We diagnosed this case as löffler's endocarditis and performed surgical treatment because medical treatment was unsuccessful. Removal of the thrombus the bilateral ventricles, endocardectomy and mitral valve replacement were performed. Endocardectomy required close attention because the border between thickened endocardium and normal myocardium was obscure. The patient survived surgery, but postoperative echocardiography (15 days) revealed slightly thickened endocardium of the right ventricle. He died of left heart failure 1 month after surgery. At that time, eosinocyte count was 110,000/mm3.
The technique of open distal anastomosis or application of aortic balloon occlusion catheter designed to occlude the descending thoracic aorta have been used in 33 and 19 patients, respectively, to control bleeding during the procedure of distal anastomosis for complete aortic arch replacement with a prosthetic graft. These two techniques allowed us a simple approach to the lesion and the avoidance of clamp injury to the fragile aortic tissue. Open distal anastomosis was applied for 91% patients of operated aortic dissection and all emergent cases, it's duration ranged from 10 to 110 minutes with an average of 58 minutes under 18.2 degrees C of lowest esophageal temperature. On the other hand, aortic occlusion balloon was inserted for mainly true aortic aneurysm patients without an emergency, and helped to maintain the perfusion pressure on a lower part of body around 50 mmHg by the 1550 ml/min in an average of perfusion flow femoral artery under 21.2 degrees C of temperature. The difference of postoperative renal and liver function evaluated by serum enzyme levels of total bilirubin, GOT, GPT, LDH, creatinine and BUN did not reach to statistical significance between the patients using open distal anastomosis and balloon occlusion, however, the incidence of postoperative complication including either renal, liver dysfunction, abdominal problem or paraplegia was significantly higher in the patient group with open distal technique. Either open distal anastomosis or aortic balloon occlusion technique would be appropriately selected according to the patient's characteristics or the condition of aortic disease to be operated.
The extramammary Paget's disease of anogenital area is rare, and is seen as a precancerous lesion or carcinoma in situ. In most cases, surgical treatment including dissection of regional lymph nodes, skin resection and grafting should be considered first. A 74-year-old male suffered from effort angina and underwent triple coronary artery bypass grafting (CABG) including saphenous vein graft (SVG) harvested from right lower leg. Five years previously he underwent skin grafting for extramammary Paget's disease of both inguinal areas and the perineal area. The postoperative course was uneventful and he was discharged 23 days after the CABG operation. Extramammary Paget's disease is localized in epidermis for years and there has been no report of direct invasion into vessels. Therefore, there appears to be no reason not to use an SVG if there is no luminal thrombus or occlusion.
We evaluated the coronary artery bypass grafting (CABG) for the cases which were not amenable to preoperative left ventriculograms (LVG). Between June 1970 and March 1996, we had 2045 cases of isolated CABG, and 52 cases of which were not amenable to preoperative LVG. The reasons of no preoperative LVG were during cardiopulmonary resuscitation (CPR) in 4 cases, shock state in 14, NYHA class IV or CCS class IV in 26, angina attack after coronary angiography in 3 and so on. Preoperative diagnoses were acute myocardial infarction in 28, angina after infarction in 13, unstable angina in 9 and effort angina in 2. Preoperative conditions were reoperation in 6, insertion of intra-aortic balloon pumping in 46, chronic renal failure in 15 (hemodialysis in 4) and arrhythmia (VT or Vf) in 12. Concerning the coronary lesions, left main trunk and triple vessel diseases occupied 75% of all. Surgical deaths were 5 cases (9.6%) and hospital deaths were 4 cases (7.7%). The all cases which needed preoperative CPR were died with brain injury. The result of the cases which were not amenable to preoperative LVG were worse than the cases with ischemic cardiomyopathies. In conclusion, no preoperative LVG is one of the highest risk factors of all.
The effect of hANP (atrial natriuretic peptide) was investigated clinically in 40 patients who underwent isolated valve replacement. Patients were divided into four groups: aortic regurgitation (AR), aortic stenosis (AS), mitral regurgitation (MR) and mitral stenosis (MS). Each group was divided into two subgroups: one was administered hANP after the operation until leaving ICU, and the other was not administered hANP. We measured the levels of hANP and c-GMP and blood pressure, pulmonary artery pressure, central venous pressure and levels of Na, K of urine and blood prcoperatively, immediately postoperatively and 1, 2, 4, 6 hours after operation. First, to examine the relationship between preoperative level of hANP and cardiac function, the relationship between preoperative level of hANP and history of cardiac failure and pulmonary artery wedge pressure (PAWP) were evaluated. Also, we evaluated the relationship between preoperative level of hANP and each dimension on echocardiography. There was a weak statistical relationship between hANP and PAWP (row = 0.39 (p = 0.04) Pearson correlation method) and there was no statistical relationship between hANP and duration of cardiac failure (row = 0.00445 (p = 0.98) Pearson correlation method). Preoperatively Left atrial diameter (LAD) showed a statistical relationship with level of hANP in every group using Spearman correlation method. Other dimensions such as left ventricular diastolic diameter (LVDd) and left ventricular systolic diameter (LVDs) and also fractional shortening (FS) did not show a strong correlation with preoperative level of hANP. Especially, in AS group there was a strong relationship between every dimension and preoperative level of hANP. Only in MS group LAD and the level of hANP were negatively related. This finding suggests that atrial dilatation results in reduction of secretion of hANP in cases of MS on long term follow up. Finally, hNAP therapy was shown to have a continuous diuretic effect, with stable hemodynamics.