The effects of a neutrophil elastase inhibitor on the postoperative respiratory failure of acute aortic dissection.

BACKGROUND: Postoperative respiratory failure is often encountered in patients suffering from acute aortic dissection (AAD) and is believed to be influenced by release of neutrophil elastase after cardiopulmonary bypass. Sivelestat is a specific neutrophil elastase inhibitor, and this study aims to evaluate the effects of sivelestat on postoperative respiratory failure due to AAD. METHODS AND RESULTS: Patients who were operated for AAD from January 2000 to April 2005 and who had less than 300 mmHg initial postoperative PaO (2)/FiO (2) were investigated retrospectively and divided into two groups. Group 1 (n = 9) received intravenous administration of sivelestat immediately after the operation, while Group II (n = 9) received no sivelestat. There were no significant differences between Group I and II with respect to patients' characteristics or background (age, body weight, operating time, cardiopulmonary bypass time, amount of bleeding, preoperative WBC number and initial PaO (2)/FiO (2)). Though patients in Group I showed a subtle improvement in certain parameters such as PaO (2)/FiO (2), A-aDO (2) and respiratory index (RI) over a 3-day observation period compared to those of Group II, there were no significant differences. Neither postoperative mechanical ventilation time nor ICU stay differed between Group I and II. However, Group I showed a significantly greater improvement in the ratio of RI to initial RI on the 3POD compared to that of Group II (61.6 +/- 44.2 % vs. 111.9 +/- 40.9 %, P = 0.02). CONCLUSION: Inhibiting the activity of the neutrophil elastase may attenuate the postoperative respiratory complications of patients with AAD.

Expression of basic fibroblast growth factor and its receptor-1 in cardiac myxoma.

BACKGROUND: To clarify the significance of basic fibroblast growth factor (bFGF) in angiogenesis or proliferative activity in cardiac myxoma, the expression of bFGF and its receptor (FGFR-1) were immunohistochemically examined. METHODS: Formalin-embedded tissues of cardiac myxomas were obtained by surgical resection from 15 patients and analyzed by immunostaining of bFGF and FGFR-1. The microvessel density was measured in the 15 myxomas using platelet derived endothelial cell adhesion molecule-1. For evaluation of proliferative activity of the cardiac myxomas, proliferating cell nuclear antigen (PCNA) immunostaining was performed, and the PCNA labeling index was measured in each section. RESULTS: bFGF and FGFR-1 were observed in 73.3% and 67.7% of the myxomas, respectively. There was a close correlation between the expression of bFGF and FGFR-1. This co-expression was frequently observed in the myxoma cells around the microvessels appearing as a ring structure. Regarding possible relationships between the expression of bFGF or FGFR-1 and the clinicopathologic features, there were no parameters excluding the macroscopic type of myxoma. The microvessel density in the myxomas with bFGF or FGFR-1 expression was higher than that in myxomas without it. The PCNA labeling index in myxomas with bFGF expression was higher than that in myxomas without it, and the PCNA labeling index tended to be higher in myxomas with FGFR-1 expression than that in myxomas without it. CONCLUSIONS: bFGF and/or FGFR-1 was expressed in some of cardiac myxoma, and may be an important role for tumor angiogenesis and proliferative activity.

[Peak expiratory flow (PEF)].

Controlling drugs and relieving drugs are prescribed for many of the patients and they use their drugs when their symptoms are getting worse. It is still controversial whether that decision should be made on the basis of the patient's perception or PEF. Some studies suggest the significance of peak flow monitoring (PFM), while others are negative about introduction of PEF. Patients tend to underestimate their symptoms, since they cannot evaluate their airway obstruction correctly. It is known that patients without PEF meters are at higher risk of dying from asthma. This review attempts to infer the significance of PEF and PFM especially in the management of adult asthmaticus.

Early growth-response factor 1 and basic transcriptional element-binding protein 2 expression in cardiac allografts.

Early growth-response factor 1 (Egr-1) and basic transcriptional element-binding protein 2 (BTEB2) are transcriptional factors that regulate multiple genes involved in phenotypic changes of smooth muscle cells (SMCs), one of the outstanding pathologic features of chronic cardiac allograft rejection. In this study, we used a heterotopic abdominal heart transplant model in monkeys to evaluate the roles of these molecules in graft coronary vasculopathy. We demonstrated that Egr-1 and BTEB2 are induced in vascular SMCs of rejected cardiac allografts well before morphologic changes, such as intimal thickening. These findings suggest that expression of Egr-1 and BTEB2 is one of the initial events in allograft angiopathy.

[Clinical characteristics of asthmatics who stop peak expiratory flow monitoring (PFM)--analysis of patients who continued PFM more than eight weeks].

To estimate the effect of treatment and for patient education, we recommend 8 weeks PFM for all asthmatics when we start their treatments. To elucidate clinical characteristics of asthmatics who stop PFM, we analyzed 311 patients (145 males aged 15-76 years and 166 females aged 17-79 years) who could measure their PEFs twice daily for more than 8 consecutive weeks. The analysis of cumulative continuation rate of PEF monitoring revealed that the patients' withdrawal rate was 19% per year. The sixty asthmatics who gave up monitoring their PEFs (group A) showed significantly younger present ages (38.8 +/- 14.2, mean +/- S.D.) and younger ages of onset of their asthma (29.8 +/- 19.6) than the other 251 asthmatics who could continue to monitor their PEFs (group B). The present ages and ages of onset of asthma of group B were 46.2 +/- 16.7 and 37.6 +/- 21.2 years, respectively. Despite no significant differences in the severity of the asthma based on both clinical symptoms and PEF between groups A and B, the asthma severity based only on the clinical symptoms of group A were significantly less than those of group B. The analysis of Cox's proportional hazards model revealed that major factors which influence patients' stopping of PFM were present age and severity of their asthma which was estimated by the patients' symptoms only, without PEF assessment. These results suggest that asthmatics whose present age is young and whose ability of perception of asthma is poor will be apt to stop PFM.

Expression of membrane-type 1 matrix metalloproteinase in coronary vessels of allotransplanted primate hearts.

BACKGROUND: The mechanisms of intimal thickening in cardiac allograft vasculopathy (CAV) remain controversial after heart transplantation. Matrix metalloproteinase-2 (MMP-2) plays a crucial role in degrading extracellular matrix (ECM) during neointimal formation. Recently, it has been revealed that MMP-2 is activated by membrane-type 1 matrix metalloproteinase (MT1-MMP). This process involves tissue inhibitor of MMP-2 (TIMP-2), forming an MT1-MMP/TIMP-2/pro-MMP-2 complex. In this study, we hypothesize that these components contribute to the pathogenesis of CAV. METHODS: Heterotopic cardiac allografting was performed in randomly paired Japanese monkeys with an immunosuppressive regimen of intravenous administration of antihuman CD18 monoclonal antibody. The donor hearts were harvested at Days 22, 28, 40, 41, and 95 posttransplantation. We examined expression of MMP-2, MT1-MMP, and TIMP-2 of graft vessels using immunohistochemistry and protein level by western blot analysis. RESULTS: Pathologically, various degrees of neointimal formation were observed. In the allografts harvested at Days 22, 28, 40, and 41, MT1-MMP was expressed in the endothelial cells and smooth muscle cells (SMCs) in media of some arteries without histological change, accompanied by expression of MMP-2 and TIMP-2. In the severely thickened neointima of the allograft harvested at Day 95, MMP-2 and faint MT1-MMP were expressed in SMCs of severely thickened neointima and media; TIMP-2 expression was seen only in noncollagenous tissue of severely thickened neointima. MMP-2 protein was more intensely expressed in the allograft harvested at Day 95 than in the allograft harvest at Day 41, while TIMP-2 protein level was almost same in the 2 samples. CONCLUSION: We observed the simultaneous expression of MMP-2, MT1-MMP, and TIMP-2. Thus, ECM degradation triggered by MT1-MMP/TIMP-2/pro-MMP-2 complex could be a novel mechanism of CAV.

[Studies on surfactant replacement therapy in pediatric measles pneumonitis].

Measles pneumonitis, as well as encephalitis, is the most important complication associated with mortality in measles. Many medications including steroids and vitamin A have been applied to pediatric measles pneumonitis. However, the efficacy of such medication has not yet been established. This study is aimed at evaluating the effectiveness of surfactant replacement therapy in pediatric measles pneumonitis. Five patients (aged 1-2 years) with measles pneumonitis were transferred to our emergency center. On the transferred day, Surfactant-TA was administered by intratracheal method. After administration of surfactant, PaO2/FIO2 increased from 63.6 +/- 11.0 (mean +/- SE) to 206.2 +/- 54.1 in an hour and to 163.8 +/- 34.8 in 24. At the same time, the CO2 elimination and the dynamic compliance were improved. Because of these effects, the peak inspiratory pressure employed in mechanical ventilation could be reduced. It is concluded that surfactant replacement therapy can prevent the patients with measles pneumonitis from hypoxemia and ventilation-induced lung injury. However, further study is needed to maintain the improved oxygenation. Recently, it is reported that the effect of exogenous surfactant on oxygenation and activity of pulmonary neutrophils is regulated by the amount and/or concentration of administered surfactant. Therefore, it is an urgent issue to find out the optimum amount and concentration of exogenous surfactant used clinically.

[A case of Salmonella subdural empyema developed in chronic subdural hematoma].

A case of Salmonella subdural empyema developed in chronic subdural hematoma (Infected Subdural Hematoma; ISH) was reported. A 64-year-old man had been in a nearby hospital due to myelodysplastic syndrome with cerebral infarction for two months. His condition there had been almost uneventful. But spike fever occurred and the patient became drowsy two days before his transfer to our medical center. His consciousness level deteriorated progressively and CT scan showed a right chronic subdural hematoma. He had had no history of head trauma in the previous two months. On admission to our center, his consciousness level was semicoma with anisocoria. An emergency operation was performed via a single burr hole initially. From the burr hole, old bloody fluid accompanied by yellowish pus was obtained. Thus so-called ISH was diagnosed and the craniotomy was carried out. Gram stain of the specimen revealed gram negative rods. Although an epileptic state developed after the operation, it was controlled by barbiturate coma therapy for 3 days, followed by phenytoin administration. Fever subsided gradually with antibiotics sensitive to the bacteria and his anisocoria disappeared on the 4th postoperative day. In this case, Salmonella enteritidis was detected from bacterial culture both of the specimen and of the arterial blood. Salmonella enteritidis might have been implanted on the capsule of the chronic subdural hematoma by bacteremia derived from immunological dysfunction due to myelodysplastic syndrome. In conclusion, the possibility of ISH should be considered in chronic subdural hematoma patients with immunological dysfunction.

Blood purification for crush syndrome.

At least 372 people developed crush syndrome after they were injured by the Great Hanshin-Awaji Earthquake. Of these, 23 were transferred to Osaka City General Hospital from the disaster area. The serum creatinine kinase (CK) of each of the 23 patients exceeded 10,000 IU/L. Sixteen of these patients were treated with various methods of blood purification including hemodialysis (HD), plasma exchange (PE), and continuous hemodiafiltration (CHDF). The effectiveness on each method of blood purification was evaluated in this study based on the clearance of myoglobin and the length of time until recovery from acute renal failure (ARF). None of the patients died, and none suffered from ARF longer than 2 months. The length of time required for blood purification was significantly correlated with the serum CK and myoglobin levels on admission. The serum myoglobin levels decreased linearly regardless of the method of blood purification used. Our findings showed that the severity of ARF that occurred in association with crush injury was proportional to the amount of crushed muscle and that once ARF had developed, the clearance of myoglobin was not affected by any of the blood purification methods tested including HD, PE, and CHDF. Therefore, the method of blood purification employed for crush syndrome should be selected for its effectiveness in treating ARF, rather than the elimination of myoglobin.

[Comparison of different types of peak flow meter and reference values for peak expiratory flow (PEF) for healthy Japanese subjects].

Any observed value of PEF in a given subject must be assessed by comparing it with that achieved by a normal healthy individual of the same race, sex, age, and, height. I introduce reference values for PEF for healthy Japanese subjects (established in 1995) for this purpose. During our survey, however, we observed considerable differences in references obtained by four different types of PEF meter (mini-Wright, Assess, Personal Best, and Vitalograph). This is an important observation that warrants our further investigation.

[Cardiac injury successfully treated by emergency cardiorrhaphy--a report of 5 cases].

Five cases who were successfully treated for cardiac injuries by emergency cardiorrhaphy were reported. The range of the ages of the patients was 14 to 71 years. Four of the 5 were males with stab wounds and one was a 71-year-old female with a blunt injury by motor vehicle accident. As to the site of cardiac wounds, all of the cases suffered single chamber injury. In the cases of stab wounds, the right atrium was involved in one case and the right ventricle was involved in the three others. The site of the blunt injury was the left auricle. However there was only one case with the pre-operative diagnosis of cardiac injury. The emergency room thoracotomy was done in 2 cases. One was stab injury and the other was blunt trauma. Both of them had an uneventfull post-operative course without any infection. In conclusion, ERT is most helpful when used in the cases with PI* < or = 15. *: physiologic index (Ivatury).

[Standard range of peak expiratory flow in normal, healthy Japanese subjects].

The measurement and analysis of the standard range of peak expiratory flow (PEF) in normal, healthy Japanese is necessary at any cost to facilitate bringing the Japanese Guidelines for Bronchial Asthma smoothly into effect. In a study as part of The Bronchial Asthma Group of the Comprehensive Research Project (Terumasa Miyamoto, Chairman of the Planning and Evaluation Committee) under the auspices of the Ministry of Health and Welfare, we measured PEF in 2,785 healthy Japanese volunteers (1,407 males aged 15-84 years and 1,738 females aged 15-80 years) who had no history of smoking, respiratory and/or thoracic diseases, or wheezing with four different peak flow meters (e.g., mini-Wright, Assess, Personal Best and Vitalograph). As a result of comparing PEF measured by the four meters in the same subjects over a short interval of time, we noted significant differences on analysis of variance. Accordingly, the equation for prediction should account for variables in gender and the type of peak flow meter used. A comparison of cubic equations for prediction suggests that the PEF of both Japanese men and women is similar to that of the British but is different from that of the Chinese.

[Death due to pulmonary tuberculosis--a comparison between 1984-88 and 1989-93].

Pulmonary tuberculosis (TB) remains the single leading cause of death from any single infectious agent in the world. We reviewed the case records and chest radiographs of patients with pulmonary tuberculosis who died between 1984 and 1993. Of 2333 patients discharged from National Nishi-Niigata Hospital, 86 (3.7%) died during that period. Comparison between the data for 1984-88 and for 1989-93 showed an increase in the number of elderly patients, TB-related deaths, and complication of TB by malignancy. Thirty-nine of the 86 patients died within 2 months of admission: a spread of TB over a wide region and low performance scores were noted in these patients. Multiple-drug-resistant Mycobacterium tuberculosis was often the cause of death. These results encourage us to pursue early detection in elderly people, to improve management during initial treatment such as with steroids, and to develop new and more effective drugs to treat TB.

Increased plasma level of platelet-activating factor (PAF) and decreased serum PAF acetylhydrolase (PAFAH) activity in adults with bronchial asthma.

We evaluated the plasma level of platelet-activating factor (PAF), a chemical mediator that induces various symptoms of bronchial asthma, and the activity of serum PAF acetylhydrolase (PAFAH), an enzyme that specifically inactivates PAF, in adults with bronchial asthma. Measurements were made by radioimmunoassay of samples obtained from 137 adult asthmatic patients (137 cases examined in remission and from among these 41 cases were also measured at the time of an asthmatic attack) 59 adult patients with untreated pulmonary tuberculosis and 106 healthy adult volunteers. It was demonstrated that the plasma PAF level was markedly higher and the serum PAFAH activity markedly lower in the asthmatic patients, both in remission and at the time of asthmatic attack, than in the healthy volunteers. The plasma PAF level was more closely associated with asthma both in remission and at the time of asthmatic attack than with pulmonary tuberculosis, whereas there was no significant difference in the serum PAFAH activity between the two diseases. The low serum PAFAH activity in the asthmatic patients may have been due to saturation as a result of continuous reaction to the increased plasma PAF level in those patients.