Hemodynamic effects of bolus nicorandil compared with nitroglycerin.
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Biomedical subjects
Publications and source records attributed to T Hirata.
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A single dose of synthetic surfactant was administered prophylactically to premature neonates with birth weights between 700 and 1100 gm. The effects of this treatment on neurodevelopmental, neurologic, and ophthalmologic outcomes, impairments, and general health status were examined during a follow-up evaluation at 1-year adjusted age. The study was a multicenter, parallel, randomized, double-blind comparison of 446 infants who received either air placebo (n = 222) or synthetic surfactant (n = 224). Follow-up evaluations were completed for 82% of surviving infants in both treatment groups. Neurodevelopmental outcome and growth were equivalent in the infants treated with synthetic surfactant and in the infants given air placebo. Impairments occurred in 38% of the infants treated with air placebo compared with 31% of those given synthetic surfactant; the difference was not statistically significant (relative risk 0.809, 95% confidence interval 0.585, 1.119). The incidence of asthma was significantly higher in the group of infants given air placebo (4% vs 10% for surfactant and air placebo, respectively, relative risk 0.391, 95% confidence intervals 0.157, 0.972). Other outcomes, including retinopathy of prematurity, hospital readmissions, surgery, and evidence of chronic lung disease, were not different. Administration of a single prophylactic dose of synthetic surfactant increases survival in infants with birth weights between 700 and 110 gm without increasing the number or proportion of impaired survivors.
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We developed a new solution, ET-Kyoto (ET-K) solution, and compared its efficacy in 20 h lung preservation with that of Euro-Collins (EC) solution in a canine left lung transplantation model. The lungs were flushed with ET-K solution (ET-K group, n = 5), with EC solution plus prostaglandin E1 (PGE1) pretreatment (EC + PGE1 group, n = 6) or with EC solution (EC group, n = 6), and were stored at 4 degrees C for 20 h. The function of left lung grafts was assessed 40, 70, and 130 min after transplantation. The arterial pressure of oxygen (PaO2) in the ET-K group was significantly greater than in the EC + PGE1 group (p < 0.05 or p < 0.01) and in the EC group (p < 0.01). The peak inspiratory pressure and wet to dry weight ratio in the ET-K group were significantly lower than in the EC + PGE1 group and in the EC group (p < 0.05 or p < 0.01). Pulmonary vascular resistance in the ET-K group 130 min after reperfusion was significantly lower than in the EC group (p < 0.05). All the transplanted lungs in the EC + PGE1 group and the EC group showed histological evidence of pulmonary edema, whereas all in the ET-K group showed no signs of edema. We concluded that ET-K solution is superior to EC solution with or without PGE1 pretreatment in 20 h canine lung preservation.
Acute hyperammonemia causes cerebral edema, elevated intracranial pressure and loss of cerebral blood flow (CBF) responsivity to CO2. Inhibition of glutamine synthetase prevents these abnormalities. If the loss of CO2 responsivity is secondary to the mechanical effects of edema, one would anticipate loss of responsivity to other physiological stimuli, such as hypoxia and changes in mean arterial blood pressure (MABP). To test this possibility, pentobarbital-anesthetized rats were subjected to either hypoxic hypoxia (PaO2 approximately 30 mm Hg), hemorrhagic hypotension (MABP approximately 70 and 50 mm Hg), or phenylephrine-induced hypertension (MABP approximately 125 and 145 mm Hg). CBF was measured with radiolabeled microspheres. Experimental groups received intravenous ammonium acetate (approximately 50 mumol min-1 kg-1) for 6 h to increase plasma ammonia to 500-600 microM. Control groups received sodium acetate plus HCl to prevent metabolic alkalosis. The increase in CBF during 10 min of hypoxia after 6 h of ammonium acetate infusion (84 +/- 19 to 259 +/- 52 ml min-1 100 g-1) was similar to that after sodium acetate infusion (105 +/- 20 to 265 +/- 76 ml min-1 100 g-1). Cortical glutamine concentration was elevated equivalently in hyperammonemic rats subjected to normoxia only or to 10 min of hypoxia. With severe hypotension, CBF was unchanged in both the ammonium (80 +/- 20 to 76 +/- 24 ml min-1 100 g-1) and the sodium (80 +/- 14 to 73 +/- 16 ml min-1 100 g-1) acetate groups. With moderate hypertension, CBF was unchanged. With the most severe hypertension, significant increases in CBF occurred in both groups, but there was no difference between groups. We conclude that hypoxic and autoregulatory responses are intact during acute hyperammonemia. The previously observed loss of CO2 responsivity is not the result of a generalized vasoparalysis to all physiological stimuli.
To investigate the clinical effects of MS-551, a Class III antiarrhythmic agent, 11 patients underwent electrophysiological study. MS-551 was given intravenously as an initial dose of 0.2 or 0.3 mg/kg for 5 minutes followed by the continuous infusion at 0.2 or 0.3 mg/kg for 30 minutes, respectively, in all patients. The rate corrected QT interval increased significantly from 3 minutes after the beginning of MS-551 infusion. The sinus heart rate decreased significantly by 8% at 10 minutes after the drug administration (P < 0.025). Mean PR and QRS intervals, and blood pressure were not significantly affected by the drug. Mean PA, AH, and HV intervals during sinus rhythm were also not affected. The effective refractory periods (ERPs) of the atrium and ventricle were significantly prolonged by 13% from 202 +/- 24 ms to 231 +/- 26 ms (P < 0.0005), and by 7% from 238 +/- 11 ms to 257 +/- 13 ms (P < 0.002), respectively, by MS-551. The ERP of the atrioventricular node and sinoatrial nodal recovery time were not changed significantly by the drug. This is a report of the effects of MS-551 in humans. This agent could be useful for treatment of tachyarrhythmias by prolongation of ERPs of the atrium and ventricle without significant variations of blood pressure and intracardiac conduction times. It is noteworthy that MS-551 slightly but significantly decreased heart rate.
The in vitro and in vivo activities of a new benzoxazinorifamycin, KRM-1648 (KRM), against Mycobacterium tuberculosis were studied. The MIC at which 50% of the isolates are inhibited (MIC50) and the MIC90 of KRM for 30 fresh isolates of M. tuberculosis measured by the BACTEC 460 TB System were 0.016 and 2 micrograms/ml, respectively. These values were much lower than those for rifampin (RMP), which were 4 and >128 micrograms/ml, respectively, and considerably lower than those for rifabutin (RBT), which were 0.125 and 8 micrograms/ml, respectively. A correlational analysis of the MICs of these drugs for the clinical isolates revealed the presence of cross-resistance of the organisms to KRM and either RMP or RBT although the MICs of KRM were distributed over a much lower range than were those of the other two drugs. KRM and RMP at concentrations of 1 to 10 micrograms/ml almost completely inhibited the bacterial growth of RMP-sensitive strains (H37Rv, Kurono, and Fujii) of M. tuberculosis phagocytosed in macrophage-derived J774.1 cells. KRM was more active than RMP in inhibiting the growth of the RMP-resistant (MIC = 8 micrograms/ml) Kurata strain but failed to show such an effect against the RMP-resistant (MIC >128 micrograms/ml) Watanabe stain. When KRM was given to M. tuberculosis-infected mice at dosages of 5 to 20 mg/kg of body weight by gavage, one daily six times per week from day 1 after infection, it was much more efficacious than RMP against infections induced in mice by the RMP-sensitive Kurono strain, as measured by a reduction of rates of mortality, a reduction of the frequency and extent of gross lung lesions, histopathological changes in lung tissues, and a decrease in the bacterial loads in the lungs and spleens of infected mice. KRM also displayed significant therapeutic efficacy against infection induced by the RMP-resistant Kurata strain, while neither KRM nor RMP was efficacious against infection by the RMP-resistant Watanabe strain. In the case of infection with the Kurono strain, the efficacy of the drugs in prolonging the time of survival was in the order KRM, RBT, RMP. KRM was much more efficacious than RMP, when given at 1- to 4-week intervals. These findings suggest that KRM may be useful for the clinical treatment of tuberculosis contracted through RMP-sensitive strains, even when it is administered at long intervals.
BACKGROUND: Active oxygen species are thought to play a part in ischaemia reperfusion injury. The ability of a novel agent, human thioredoxin (hTRX), to attenuate lung damage has been examined in a rat model of ischaemia reperfusion injury. METHODS: Twenty eight animals were studied. At thoracotomy the left main bronchus and the left main pulmonary artery were clamped for 75 minutes and the lung was then reperfused for 20 minutes. Phosphate buffered saline was administered intravenously to nine control animals and hTRX (30 micrograms/g body weight) was given intravenously to another group of nine animals. Two experiments were carried out. The first (Exp 1) was a time matched pair experiment (five treated, five controls), and the second (Exp 2) was performed under controlled conditions (four treated, four controls; temperature 25 degrees C, humidity 65%). In another 10 nonischaemic rats and those in Exp 1 biochemical measurements of lipid peroxide, superoxide dismutase, and glutathione peroxide levels were performed. RESULTS: In both experiments rats perfused with hTRX survived longer than controls. In Exp 1 the arterial oxygen tension (PaO2) on air in the hTRX group was higher at 20 minutes than at one minute after reperfusion. In Exp 2 PaO2 at 20 minutes was higher in the hTRX group than in the controls. Lipid peroxide, superoxide dismutase, and glutathione peroxide levels in the control group were higher than in the hTRX group and in the non-ischaemic groups. Histological examination showed less thickening and oedema of the alveolar walls in the hTRX group than in controls. CONCLUSIONS: These results suggest that hTRX is effective as a radical scavenger and can limit the extent of ischaemia reperfusion injury of the lungs of experimental animals.
Neuropilin (previously referred to as A5) is a neuronal cell surface protein which is widely distributed in such vertebrate species as Xenopus, chicken and mouse. In these vertebrate species, neuropilin is expressed in particular neuron circuits at particular developmental stages when axonal growth is active. To test whether the expression patterns of neuropilin is associated with axonal growth, we examined expression patterns of neuropilin in developing and regenerating Xenopus optic nerves. In embryos, a neuropilin-specific monoclonal antibody A5 (MAbA5) bound strongly to the optic nerves, and in situ hybridization signals for neuropilin mRNA were prominent in the retinal ganglion cells (RGCs), indicating that developing optic nerve fibers express neuropilin. The binding of MAbA5 to the optic nerve fibers was maximal at stages 41-43, then decreased in the subsequent tadpole life. In tadpoles after stage 50, the binding of MAbA5 to the optic nerves was extremely weak or almost nil, although RGCs expressed considerable amounts of neuropilin mRNA. When the tadpole optic nerves were crushed and prompted to regenerate, however, neuropilin protein reappeared in the optic nerve fibers. The binding of MAbA5 to the regenerating optic nerve fibers was detectable as early as the 5th day and maximal at the 2nd or 3rd weeks after the optic nerve crush, and declined thereafter. These findings suggest that the expression of neuropilin in the optic nerve fibers is regulated in an axonal growth-associated manner.
We studied the role of human thioredoxin and L-cysteine in ischemia-reperfusion lung injury. Thirty adult Wistar rats were allocated to five groups, according to the drug added to the pulmonary artery flush solution before ischemia (groups 1 and 2: none; group 3: human thioredoxin; group 4: L-cysteine, and group 5: human thioredoxin and L-cysteine) and according to the ex vivo ischemic interval at 37 degrees C (group 1: no ischemia; groups 2-5: 90 min). After ischemia, the lungs were reperfused for 60 min with Krebs-Henseleit solution containing 4% bovine serum albumin. In nonischemic lungs, the pulmonary arterial pressure, airway pressure, wet to dry lung weight ratio and the albumin concentration in bronchoalveolar fluid were within normal ranges. In contrast, all parameters of ischemic untreated lungs were generally poor. Compared to the ischemic untreated lungs, treatment with the combination of human thioredoxin and L-cysteine significantly reduced the wet to dry lung weight ratio (group 2: 9.18 +/- 0.25, group 5: 7.88 +/- 0.27), and the albumin concentration in the bronchoalveolar lavage fluid (group 2: 78.3 +/- 17.1 micrograms/ml, group 5: 24.0 +/- 3.8 micrograms/ml). No significant improvement was found in pulmonary arterial pressure and airway pressure. These results suggested that treatment with human thioredoxin (adult T cell leukemia-derived factor) and L-cysteine attenuates ischemia-reperfusion injury in isolated rat lungs.
Catheter ablation was attempted in 2 patients with atrioventricular node reentry tachycardia which showed fast, intermediate and slow anterograde atrioventricular node pathways. Radiofrequency currents were applied within a restricted area of the tricuspid annulus between the His bundle and the ostium of the coronary sinus where presumed slow pathway potentials were identified. Elimination of both the intermediate and the slow pathways, with preservation of anterograde and retrograde fast pathway conduction, was achieved in both patients.
The effects of aprindine on atrial vulnerability were studied in 11 patients; 9 with paroxysmal atrial fibrillation (PAF), and 2 with Wolff-Parkinson-White syndrome, aged 19 to 69 (55.9 +/- 16.5; mean +/- SD). Before and 10 min after the intravenous injection of aprindine (1.5 mg/kg), programmed extrastimulation was performed from the right atrial appendage. Atrial vulnerability was assessed by evaluating the repetitive atrial firing zone (RAFZ), conduction delay zone (CDZ), maximum conduction delay (Max. CD) and fragmented atrial activity zone (FAAZ). After the injection, the duration of the P wave and QTc interval was significantly prolonged without any change in blood pressure or heart rate. RAF was observed in 8 patients under control conditions. However, after the injection of aprindine, the RAFZ completely disappeared in 2 patients, was narrowed in 4, and became wider in 1. AF was induced in the remaining patient. The zone significantly reduced (p < 0.01) without any change in CDZ or Max. CD. While FAA was observed in 5 patients under control conditions, it completely disappeared in 2 patients, was narrowed in 1, and did not change in the remaining 7 after the injection of aprindine. In patients whose RAFZ narrowed after administration of aprindine, the wavelength, as determined from the atrial effective refractory period and conduction velocity, was augmented. These results indicate that aprindine suppresses atrial vulnerability with an augmentation of the wavelength. However aprindine exaggerated atrial vulnerability in some patients, such that atrial fibrillation was induced.
Thioredoxin (TRX) production has been shown to be induced by a variety of stresses. In this study, we examined TRX expression in lung tissues after canine lung transplantation to determine whether it could be induced by allogenic stimulations and could be used to diagnose early rejection. Thirty-five adult mongrel dogs were used in all. In group A, 24 dogs underwent allotransplantation of the left lung with no immunosuppressant and were sacrificed at various times; 5 were sacrificed on postoperative day (POD) 1; 5 on POD 2; 7 on POD 3; and 7 on POD 5. In group B, 5 donor right lungs were used for negative control. In group C, 3 dogs underwent autotransplantation. In group D, 8 dogs underwent allotransplantation of the left lung with optimal immunosuppression and were sacrificed at POD 28. Lung tissues were stained with anti-TRX antibody, and the TRX high-producer (TRXh) cells in a randomly chosen field were counted as the index of TRX expression. In group A, the number of TRXh cells were as follows: 1.68 +/- 1.14 in grade 0; 4.87 +/- 1.07 in grade 1; 10.42 +/- 4.24 in grade 2; 27.34 +/- 17.96 in grade 3; and 50.90 +/- 17.36 in grade 4. In group B, the number of TRXh cells was 1.82 +/- 1.01. There was a significant difference between each rejection grade in group A and group B (p < 0.01), and we could observe TRXh cells in the early stage of rejection. These results suggest that analysis of TRXh cells in lung tissues may be useful in the early diagnosis of rejection.
Seventeen consecutive patients (3 men and 14 women, aged 14-75 years) with a hemorrhagic degeneration of the thyroid nodule, which was confirmed by both ultrasonography and either reddish or brown fluid evacuated by fine-needle aspiration, were classified as either acute type with an episode of abrupt painful swelling of the thyroid (n = 4), or chronic type in which a painless thyroid nodule was incidentally found (n = 13). One of the four acute type patients demonstrated subacute thyroiditis-like symptoms and laboratory findings including transient painful thyrotoxicosis associated with high serum levels of thyroid hormones and thyroglobulin (Tg), a suppressed serum TSH level, a low thyroidal radioactive iodine uptake (RAIU), and accelerated erythrocyte sedimentation rate (ESR). In the other three acute type patients the serum level of Tg increased markedly, the serum thyroid hormones level increased in one, the thyroidal RAIU was low in two, and the ESR was accelerated in one. In the thirteen chronic type patients, the serum levels of the thyroid hormones and the thyroidal RAIU were within the normal range, and few inflammatory signs were observed. These findings suggest that acute hemorrhagic degeneration of the thyroid nodule may thus cause transient subacute thyroiditis-like symptoms and laboratory findings.
A 46-year-old woman with incidentally discovered thyrotropin (TSH)-producing pituitary adenoma showed endocrine data which was consistent with TSH-producing pituitary tumor. However, she showed only slight hyperthyroidism and the oversecretion and autonomous secretion of TSH from the tumor seemed to be limited from the results of several endocrine examinations. Immunohistochemical examination revealed that not only TSH-beta and TSH-alpha but also prolactin and growth hormone synthesizing cells were present in the tumor tissue. Pituitary-transcription activator 1 (Pit-1) immunoreactivity was also detected in the adenoma cell nuclei. It was conceivable that the presented TSH-producing adenoma clinically located close to the non-functioning adenoma and Pit-1 may have played an important role in the multidirectional differentiation or development of this tumor.
Forty seven patients with hematological malignancies were treated with high doses of cytosine arabinoside (Ara C; 12 g/m2) and etoposide (VP-16), followed by recombinant human granulocyte colony-stimulating factor (rhG-CSF; 50 micrograms/m2). Peripheral blood progenitor cells (PBPC) were collected during rapid leukocyte recovery using a CS-3000 blood cell separator. A blood volume of 9 liters was processed in each apheresis, with 162 apheresis procedures performed. The mean numbers of mononuclear cells (MNC) and colony-forming unit granulocyte-macrophage (CFU-GM) harvested per apheresis were 4.4 x 10(8)/kg and 142.5 x 10(4)/kg, respectively. A sufficient number of CFU-GM for engraftment (> 30 x 10(4)/kg) could be harvested by a single apheresis in 35 of 47 patients (74%). Various factors that influence the collection of progenitor cells were analyzed by univariate and multivariate analyses. The number and duration of previous chemotherapy cycles were the most significant factors affecting CFU-GM yield. In patients with malignant lymphoma, age also had an influence in addition to these two factors. MNC harvested had an impact on CFU-GM yields by univariate analysis. These observations suggest that high-dose Ara C plus VP-16 followed by G-CSF is an effective regimen for harvesting PBPC. PBPC should be collected in the early stage of first-line chemotherapy.
A 47-year-old male was admitted because of an abnormal shadow on chest X-ray. Computed tomography showed a giant bulla in the right lung. The giant bulla was resected under thoracoscopic guidance using endoscopic GIA by three puncture technique. The thoracoscope was inserted through the 5th intercostal space in the mid-axillar line. The forceps was inserted through the 5th intercostal space below the inferior angle of the right scapula. The Endo GIA was inserted through the 3rd intercostal space in the anterior axillar line. The residual lung expansion was good enough. The chest drain was removed 5 days after operation thoracoscopic surgery with Endo GIA can be useful in treatment of patients with emphysematous giant bulla.
The relationship between oxygen delivery (DO2) and oxygen consumption (VO2) was studied in thirty patients who underwent open heart surgery. Delivery dependent consumption was observed for the first 48 hours after the surgery even DO2 was in a physiological range (> 300 ml/min/m2). VO2 decreased in proportion to a decrease in DO2 (VO2 = 0.132 x DO2 + 87.9, R = 0.616, p < 0.001). Oxygen extraction rate (ER = VO2/DO2) increased also in proportion to a decrease in DO2 (ER = -0.385 x DO2 + 51.8, R = -0.722, p < 0.001). These results suggest that tissue oxygen demand in the early postoperative period is higher than physiological conditions. Factors which directly influenced ER were cardiac index (CI) and hemoglobin (Hb) as expressed in the following formulas; ER = -6.05 x CI + 51.6 (R = -0.592, p < 0.001), ER = -2.02 x Hb + 56.7 (R = -0.414, p < 0.001). This indicates that hypoperfusion and anemia deteriorate oxygen metabolism in the early postoperative period. As a monitor of oxygen demand, oxygen saturation of mixed venous blood (SvO2) was an useful parameter to indicate the ER (ER = -0.872 x SvO2 + 91.9, R = -0.969, p < 0.001).