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Because we experienced each 1 operative case of diffuse malignant mesothelioma of the pleura and pseudomesotheliomatous carcinoma of the lung discovered with pleural effusion, clinical comparison investigated both. The first case was suspected diffuse malignant mesothelioma of the pleura before operation, and we performed pleuropneumonectomy. But the pathologic diagnosis was adenocarcinoma of the lung, what is so called pseudomesotheliomatous carcinoma. The second case had inhaled asbestos and his pleural effusion revealed high concentrations of hyaluronic acid. Thoracoscopic biopsy showed malignant mesothelioma, and we performed pleuropneumonectomy. The pathologic final diagnosis was diffuse malignant mesothelioma of the pleura. In clinical differential diagnosis of diffuse malignant mesothelioma of the pleura and pseudomesotheliomatous carcinoma of the lung, history of inhalation of asbestos and concentrations of hyaluronic acid in pleural effusion are helpful. And thoracoscopic biopsy is necessary in established diagnosis.

SMON (subacute myelo-optico-neuropathy) may result from clioquinol neurotoxicity. An 81-year-old woman underwent internal fixation for left intertrochanteric fracture. She had been diagnosed as having SMON twenty years previously. Sensory examination revealed paresthesia and decreased deep sensation in the lower extremity. A recent neuropathological report shows that in long-term SMON of about fifteen years, degeneration is located from the medulla oblongata to T5-6. We performed spinal anesthesia of which the level of analgesia was below T5-6 in the present case. The level of anesthesia was determined by the pinprick test, and was recognized as below T10. Postoperatively, both the sensory level of analgesia and vital signs remained stable. There was no worsening of neurological findings after spinal anesthesia, including the postoperative period. In conclusion, spinal anesthesia which was limited to below the level of degeneration could be applied in a case of long-term SMON.

A 59-years-old male patient who had left upper lobe partial resection 30 years ago. He was seen at the family physician because of cough. A chest X-ray was showing an abnormal mass shadow measuring 3 x 4 cm in left lower lobe like honey comb. And squamous cell carcinoma (SCC) was detected in his sputum. He was diagnosed as primary lung cancer and introduced to our department to have operation. Chest CT-scan was showing lung tumor suspected SCC measuring 4.3 x 2.6 cm in segment 8 faced chest wall. At the same time, we detected thoracic aortic aneurysm and subcarinal lymph node, but could not see where the boundary is, so it was hard to distinguish between parietal thrombus with thoracic aortic aneurysm and swelling subcarinal lymph node. We decided it swelling subcarinal lymph node by three-dimensional treated CT-scan. Aortic angiography was showing proximal descending aortic aneurysm measuring diameter was 4.5 cm. Abdominal CT-scan was showing infrarenal abdominal aortic aneurysm measuring diameter was 5.5 cm. He was diagnosed as primary lung cancer (It. S8, SCC) (cT2N2M0, Stage IIIB), thoracic aortic aneurysm, abdominal aortic aneurysm, and idiopathic pulmonary fibrosis, and had completion pneumonectomy (R 2 b) for primary lung cancer and graft replacement with aneurysm dissection for thoracic aortic aneurysm without extracorporeal circulation. In this operation, we could find swelling subcarinal lymph node measuring 5 x 3 cm instead of parietal thrombus with thoracic aortic aneurysm. Pathological examination diagnosed middle differential SCC and no metastasis from dissected lymph node (PT2N0M0, Stage I A).

Solid dispersion composed of the poly(ethylene oxide) (PEO)-carboxyvinylpolymer (CP) interpolymer complex containing phenacetin (PHE) was prepared by using nine grades of PEO having different molecular weights from 2000 to 4500000. We attempted to control the medicine release from the PEO-CP solid dispersion by varying the molecular weight of PEO. The physicochemical properties of the solid dispersion were analyzed by powder X-ray diffractometry and thermal analysis. The interaction between PEO and CP was analyzed by IR spectroscopy. Transmittance of the polymer solution was measured to study the complexation between PEO and CP. The release profile of PHE varied depending on the molecular weight of PEO. The minimum release rate was observed at the PEO molecular weight of 35000. It was found that the amount of the PEO-CP complex formation by hydrogen bonding changed depending on the molecular weight of PEO. These results indicate that it is feasible to control the medicine release from the PEO-CP solid dispersion by varying the molecular weight of PEO.

Mexiletine, an antiarrhythmic agent, was preincisionally administered intravenously for the purpose of reducing postoperative pain. Twenty-eight female patients for mastectomy were studied. The patients were divided into three groups. Group 1 received no mexiletine. Group 2 received bolus administration of mexiletine 1 mg.kg-1 with additional continuous administration of 1 mg.kg-1.hr-1 for 75 minutes. Group 3 received bolus administration of mexiletine 2 mg.kg-1. The requirement of butorphanol as a postoperative analgesic within 1 hour after mastectomy in Group 3 was significantly lower than that in Group 1 (P0.05), but butorphanol requirement in Group 2 was not significantly lower than that in Group 1. Plasma mexiletine concentration was slightly higher in Group 3 (1.7 micrograms.ml-1) than that in Group 2 (1.0 microgram.ml-1) immediately after the intravenous mexiletine administration, although there was no significant difference. The results indicate that mexiletine 2 mg.kg-1 as preoperative bolus administration maintains its plasma concentration above 1.7 micrograms.ml-1, and is clinically effective for reducing the postoperative pain after mastectomy.

The purpose of this study was to evaluate the changes of blood flow of the submandibular gland in comparison with salivary secretion after gustatory stimulation through use of color Doppler sonography.High-frequency color Doppler sonography was performed on 30 healthy volunteers, aged 22 to 31 years. The prestimulation and poststimulation arterial blood flows were evaluated with color Doppler sonography and spectral analysis.The means of prestimulation maximum and minimum velocities and pulsatility index of the submandibular gland were 6.35 +/- 2.57 cm/sec, 1.79 +/- 0.93 cm/sec, and 1.53 +/- 0.42, respectively. After the stimulation, the color signals and velocities increased and the pulsatility index decreased. There was a close correlation between the increase in minimum velocity and that of salivary secretion.Color Doppler sonography is useful in analyzing changes in the blood flow of the submandibular gland caused by gustatory stimulation.

A 51-year-old man with dilated cardiomyopathy, who had been treated with medication for five years, was scheduled for abdomioperineal resection of the rectum. Preoperative echocardiography demonstrated left ventricular dilation and hypertrophy, with an ejection fraction of 0.34. Anesthesia was induced with ketamine 40 mg and fentanyl 0.5 mg intravenously. Endotracheal intubation was facilitated by administration of vecuronium 10 mg. Anesthesia was maintained with nitrous oxide-oxygen-sevoflurane and fentanyl. In order to regulate myocardial contractility and after-load, use of a phosphodiesterase III inhibitor was considered, although phosphodiesterase III inhibitors are known to induce arrhythmias, which should be avoided in dilated cardiomyopathy patients. We chose olprinone, because its inotropic action is not associated with arrhythmogenecity. Before infusing olprinone, cardiac output was 4.5 l.min-1 and systemic vascular resistance was 1306 dynes.sec.cm-5. When olprinone was continuously infused for one hour, cardiac output increased to 5.2 l.min-1 and systemic vascular resistance decreased to 958 dynes.sec.cm-5. Some premature ventricular contractions occurred, but they were easily controlled by administration of 50 mg lidocaine. These clinical data demonstrate that olprinone enhanced myocardial contractility, and decreased after-load and arrhythmogenecity in a dilated cardiomyopathy patients. In conclusion, olprinone is useful in the perioperative cardiovascular management of surgical patients with dilated cardiomyopathy.

It is generally accepted that early human prostate cancers reveal higher androgen dependency than do advanced ones. In the present study, we examined whether the animal model of prostate cancer has already lost androgen dependency at the early stages of carcinogenesis. At experimental week 46, androgen deprivation was induced in rats and the incidences of atypical hyperplasia and cancer were examined in the ventral, dorsolateral prostate, coagulating glands, and seminal vesicles. Androgen deprivation significantly lowered the incidence of atypical hyperplasia in all four organs. As for the incidence of cancer, no significant differences were observed in the coagulating glands and seminal vesicles. Regarding atypical hyperplasia, androgen deprivation significantly decreased the proliferative cell nuclear antigen labeling index in the coagulating gland and seminal vesicles. The presence of cancer was also decreased in the coagulating gland but not in the seminal vesicles. With control group specimens, more intense staining of androgen receptor was observed in atypical hyperplasias than in cancers. Compared with the atypical hyperplasias, the cancers revealed low androgen dependency at the early stages of carcinogenesis. The cancers in the seminal vesicles also revealed higher androgen independency than did those in the coagulating gland.

Although survival analysis dealing with right-censored data has enjoyed wide use, analysis of data with left-censored and interval censored cases is available only to a very limited number of clinical researchers because of the difficulty in understanding the concepts and performing the calculations. This paper applies Turnbull's self-consistency algorithm, which he applied in his paper on survival data with only left-censored cases, for nonparametric estimation of survival curve including both left and interval censored data. A difference in the estimates of survival rate among different modes of calculation was demonstrated using the data from the Hematopoietic Cell Transplantation Registry of the Japan Society for Hematopoietic Cell Transplantation, which illustrated the necessity of a correct analysis.

We assessed the clinical efficacy and determined the effective dose of erythropoietin (EPO) in 48 children scheduled for open heart surgery without blood transfusion. The children were divided into three groups: group 1 (n=21) was treated with 300 U/kg of EPO; group 2 (n=11) was treated with 150 U/kg of EPO; and group 3 (n=16) was not treated with EPO. EPO was administered on the day of hospital admission (6 to 7 days prior to surgery), on the following day, immediately after surgery, and on the following day. Immediately after surgery, the hemoglobin concentration in groups 1 and 2 was significantly higher than that in group 3. The reticulocyte count in groups 1 and 2 was significantly higher than that in group 3. Open heart surgery was completed without transfusion in all 21 patients in group 1 (100%), 10 of 11 in group 2 (90.9%), and 11 of 16 in group 3 (68.8%). EPO caused no adverse reactions. In conclusion, EPO was effective as an adjuvant therapy for open heart surgery without blood transfusion in children. Administration of a relatively high dose of EPO (300 U/kg) seems to be effective for pediatric patients.

Kinetics of cca1, cca2, cca3 and rat gas1 mRNA levels were compared with those of DNA synthesis level in regenerating rat liver cells after partial hepatectomy. A transient decrease of cca3 mRNA level and an increase of rat gas1 mRNA level were observed before initiation of DNA synthesis, followed by a rapid decrease of rat gas1 mRNA level. By molecular cloning and nucleotide sequencing, cca3 cDNA was found to consist of 4514 nucleotides with a large open reading frame of 3027 nucleotides, encoding a protein of 1009 amino acids with three copies of an ankyrin repeat-like sequence.

A case-control study of leukemia and diagnostic X-ray exposure was conducted by a multi-institution co-operative study group. The subjects were 134 patients with acute myelogenous leukemia, 57 with chronic myelogenous leukemia, 56 with acute lymphocytic leukemia and 50 with myelodysplasia syndrome, who were between 15 and 79 years old, and diagnosed at one of 27 hospitals between September 1993 and August 1995. The controls were 479 first-visit patients seen at eight of these 27 hospitals. History of diagnostic X-ray tests between 1982 and 1991 was determined by an anonymous self-administered questionnaire. The total relative dose of radiation exposure was calculated by summing the products of given weights and frequencies of each test. The relative risk was 0.83 (95% confidence interval (C.I.), 0.58-1.19) for relative dose of 10-30 (equivalent to 4-11 times of UGI series), 0.76 (0.48-1.20) for relative dose of 30 or more (more than 12 times of UGI series), when compared with relative dose of 0-10 (0-3 times of UGI series). Analysis according to type of leukemia revealed that only acute myelogenous leukemia had an estimated relative risk above unity (1.08, 95% C.I. 0.69-1.69, for relative dose 10-30). This study did not support the hypothesis that diagnostic X-ray tests increases leukemia risk.

We discussed on the treatments for T4 lung cancer with invasion to the superior vena cava, whose prognosis has been poor. However, surgical resection may improve the prognosis compared with radiation therapy. The prosthetic replacement of superior vena cava can be done safely, and its patency is good in cases of ring-enforced ePTFE graft. Although superior vena caval obstruction syndrome had been a hard issue in the advanced cases, stenting in superior vena using the interventional radiological technique is a safe and reliable method. We should consider the stenting as the first choice for superior vena cava obstruction syndrome, because it makes the QOL improve so much.

Staphylokinase obtains plasminogen activating activity by forming a complex with plasminogen. Although the enzymatic activity of staphylokinase is enhanced by fibrin, how fibrin enhances enzymatic activity has not been determined yet. The effects of fibrin, or fibrinogen fragments, on the activation of plasminogen by staphylokinase was investigated using CNBr-digested fibrinogen fragments (FCB-2 and FCB-5) and plasmin-degraded cross-linked fibrin fragments ((DD)E complex, DD fragments and E fragments). Kinetic analysis of the activity of staphylokinase revealed that its plasminogen activating activity, which was expressed as kcat/Km, was enhanced by FCB-2 (10-fold) and FCB-5 (5-fold). These fibrin fragments caused 38-, 30-, and 8.5-fold increases in activity for the DD fragment, (DD)E complex and E fragment, respectively. Although alpha2-antiplasmin inhibited the activation of plasminogen by staphylokinase, FCB-2 abolished its inhibitory effects, and the plasminogen activating activity of staphylokinase was restored. The inhibitory effects of alpha2-antiplasmin on the activation of mini-plasminogen by staphylokinase were less than for Glu- or Lys-plasminogen, and the inhibitory effect of alpha2-antiplasmin was not altered by fibrin or EACA. These findings indicate that the staphylokinase/plasmin(ogen) complex reacts with fibrin even in the presence of alpha2-antiplasmin, and efficient plasminogen activation takes place on the surface of fibrin.

The effects of grinding and tableting on the physicochemical stability of TAT-59, (E)-4-[1-[4-[2-(dimethylamino)ethoxy]phenyl]-2-(4-isopropyl) phenyl]-1-butenyl]phenyl monophosphate, were studied. The crystallinity of TAT-59 ground in a planetary ball mill for 0-120 min or compressed at 0-4500 kg/cm2 was evaluated by X-ray diffraction analysis and differential scanning calorimetry (DSC). The surface of TAT-59 was measured under a scanning electron microscope (SEM). The physicochemical stability of TAT-59, ground or compressed, was determined by measurements of water content, crystallinity and the amount of hydrolysis product, DP-TAT-59, formed. The crystallinity of ground TAT-59 decreased with increasing grinding time, and the amount of DP-TAT-59 increased with decrease in the crystallinity. Similar to ground TAT-59, the crystallinity of TAT-59 tablet gradually decreased with increasing compression pressure, and the amount of DP-TAT-59 tended to increase with decreasing crystallinity. These findings suggested that the decrease of the crystallinity of TAT-59 by mechanical force, such as grinding and tableting, raised the drug's reactivity and affected its stability.

Cerebrovascular stroke is one of the major complications in cardiovascular surgery with cardiopulmonary bypass. The purpose of this study was to evaluate the usefulness of preoperative 99mTc-ethyl cysteinate dimer (ECD) SPECT and acetazolamide (diamox) enhancement to predict neurological complications in cardiovascular surgery. Eighteen patients with coronary disease, valvular disease or aortic aneurysm were studied before the operations. Regional cerebral blood flow and perfusion reserve were evaluated using ECD SPECT before and after the intravenous administration of diamox (1 g). Three cases with moderate to severe baseline abnormalities and poor perfusion reserve had cerebral infarction postoperatively. Twelve cases with good to fair perfusion reserve had no neurological complication. Three cases having poor perfusion reserve had the operations with more intensive brain protection, in which higher perfusion pressure to the brain was maintained during cardiopulmonary bypass, and no neurological complication was observed. In conclusion, patients who have moderately or markedly abnormal baseline flow with poor perfusion reserve may have some risk of neurological complications in cardiovascular surgery. ECD SPECT with diamox enhancement may give information useful for selection of operation procedures.

A 58-year-old man fell into a trichloroethylene reservoir bath head first, during a maintenance degreasing bath and accidentally ingested the solvent. Although he showed deep coma, chemical burns and pneumonia on admission, these symptoms gradually subsided. The concentrations of trichloroethylene (TRI) and its metabolites, trichloroethanol (TCE) and trichloroacetic acid (TCA) in blood and urine were measured during hospitalization. Eight hours after the accident, the concentrations ofTRI and its metabolites in serum were 31.4 μ g/ml TRI, 16.5 μg/ ml TCE and 79.5 μg/ml TCA. The serum TRI concentration decreased to 4.3 μg/ml on the following day. Elimination of TCE and TCA from serum occurred biphasically, the estimated half-lives of each metabolites being about 52.6 and 50.4 h in an initial fast phase and 268.3 and 277.2 h in a subsequent slow phase, respectively. Urinary TRI excretion persisted for the first 2 days. The urinary TCE and TCA excretions were longer than that of TRI with a biphasic decrease and the total amount of TCE excreted during the first 2 days was about two times that of TCA. The half-life of urinary TCE excretion (t½ 25.7 h) was shorter than that of TCA (t½ 52.1 h) in the fast phase but did no difference during the slow phase, with each half-time being about 166.3 h. The kinetics of TRI metabolites in blood and urine in this case were in slight agreement with the results following inhalation exposure previously reported in the literature.

We have already reported that estrogen treatment given to immature castrated rats caused proliferative changes in both collagen and smooth muscle in the seminal vesicles of immature rats detected by light microscopy. Herein, we studied the estrogen-induced changes in estrogen receptor (ER) in the seminal vesicles of immature castrated rats by means of enzyme immunoassay, an immunohistochemical method and RT-PCR, to clarify the mechanism of estrogen induced proliferation of collagen and smooth muscle. Immature rats (3 weeks old) were castrated and left untreated for 3 weeks and then injected subcutaneously with estradiol-17 beta (E2-17 beta, 5 micrograms/day) for 7 days before they were killed. The nuclear ER content per gland, mg tissue and mg protein in the seminal vesicles of castrated rats increased markedly compared with those of non-treated rats. Castration also enhanced ERmRNA expression. The immunohistochemical analysis demonstrated the obvious tissue distribution by which the nuclear ER positive cells were densely distributed in the periglandular stroma. The nuclear ER contents per gland, mg tissue and mg protein in the seminal vesicles of estrogen-treated castrated rats were greater than those in castrated rats. Estrogen treatment further enhanced ERmRNA expression in the castrated rats. The immunohistochemical studies demonstrated that the nuclear ER positive cells appeared among the glandular epithelial cells, basal cells and the peripheral stromal cells, in addition to the periglandular stromal cells. These findings suggest that ER is related to the estrogen induced proliferation of collagen and smooth muscle in the seminal vesicles of immature castrated rats.

The monoclonal antibody against estramustine-binding protein (EMBP) was produced by immunizing a mouse with EMBP antigen purified from rat ventral prostate. On western blotting analysis this antibody recognized the EMBP C1 component, and in an absorption test it recognized the EMBP antigen. Immunohistochemically, this antibody revealed positive staining for the ventral and dorsolateral prostate. In the epithelium of the ventral prostate, intense immunostaining was observed in the intraluminal secretory product; however, in the epithelium of the dorsolateral prostate, the staining was intense in the cytoplasm of the epithelial cells. These findings suggested differences of EMBP localization in the ventral and the dorsolateral prostate. Since the intensity of immunostaining for EMBP was decreased in the prostate of castrated rats, we considered that this antibody reflected the androgen dependency of EMBP.

A 66-year-old man was revealed an abnormal shadow in the chest roentgenogram. Definitive diagnosis was not obtained by chest CT and bronchofiberscopy. Three months later, the shadow showed a rapid increase. We made a diagnosis of lung cancer by needle biopsy. Extended radical operation for the tumor was performed. The tumor with invasion to the chest wall and the mediastinum was completely resected with reconstruction of the chest wall and SVC. Postoperative pneumonia and respiratory failure were occurred, and patient died four months later.

A 41-year-old man was admitted to our hospital complaining of severe right chest pain and dyspnea. Soon after, right thoracocentesis was done and pleural free air was aspirated. Twenty minutes later he fell into a shock status. Chest roentgenogram showed massive right pleural fluid collection. Chest drainage revealed that massive bleeding continued. Therefore, emergent thoracotomy was performed. Bleeding point was a ruptured stump of pleural adhesion of the apical parietal pleura. His postoperative course was almost good, and discharged on the tenth postoperative day. Careful observation after thoracic aspiration is necessary in the treatment of spontaneous pneumothorax.

The edema of grafted lungs during the early postoperative period is one of the serious complications of single lung transplantation for primary pulmonary hypertension.The effectiveness of inhaled nitric oxide in single lung transplantation for primary pulmonary hypertension during the early postoperative period was evaluated with the use of rats with monocrotaline-induced pulmonary hypertension. In the inhaled nitric oxide group, rats were given 60 parts par million of nitric oxide for 24 hours just after left lung transplantation; in the no inhaled nitric oxide group, rats were kept without nitric oxide inhalation; in the control group, normal rats received left isografts.Three hours after transplantation, the mean pulmonary artery pressure of the no inhaled nitric oxide group (28.0 +/- 4.6) was significantly higher than that of the control group (23.3 +/- 0.9, p0.05) and the inhaled nitric oxide group (22.7 +/- 1.7, p0.05). On the first postoperative day, the mean left-to-right pulmonary blood flow ratio in the inhaled nitric oxide group was 0.34 +/- 0.03; it showed no significant difference to those of the other two groups, whereas that of the no inhaled nitric oxide group (0.42 +/- 0.14) was significantly elevated compared with that of the control group (0.14 +/- 0.03, p0.05). Histopathologically, the edema of the grafted lungs 24 hours after operation in the inhaled nitric oxide group was less severe than that in the no inhaled nitric oxide group.The postoperative use of inhaled nitric oxide is effective to reduce the pulmonary edema of the grafts in single lung transplantation for pulmonary hypertension by reducing acute pulmonary blood flow shift toward grafts after transplantation.

Chordal replacement with expanded polytetrafluorethylene suture has become a procedure of choice for repairing anterior leaflet prolapse among certain surgeons. However, most surgeons believe that the chordal replacement is too complicated and not reproducible. This report introduces a new method of chordal replacement using intraoperative epicardial and transesophageal echocardiography. Three dogs underwent the following procedures. One major marginal chorda of an anterior mitral leaflet was resected during cardiopulmonary bypass. A specially designed 3-0 polytetrafluoroethylene suture, having straight needles, was attached to the anterior leaflet by a mattress suture. Then the needles were brought from the root of the anterior papillary muscle to the outside of the left ventricle. After the bypass flow was reduced, both ends of the polytetrafluoroethylene suture were pulled under echocardiographic guidance until valve competence was achieved. At that point, the suture was temporarily tied. When cardiopulmonary bypass was discontinued, competence was again confirmed and the suture was tied permanently. When the procedures were completed, echocardiography showed trivial regurgitation and good pliability of the anterior leaflets in all animals. Left atrial pressures were sufficiently decreased. It appears that this new technique is reproducible for all surgeons because the optimal length of polytetrafluoroethylene chordae is determined with the valve functioning.

ACE inhibitors, as well as aminocephalosporins with peptide-like structures, are transported by the intestinal peptide carrier. We investigated the transport mechanism using intestinal brush-border membrane vesicles from rabbits and observed that enalapril, an angiotensin converting enzyme inhibitor and substrate of the peptide carrier, noncompetitively inhibited the uptake of cephradine, an aminocephalosporin and substrate of the peptide carrier, with an inhibition constant (Ki) of 2.6 mM when it was present on the cis side (outside) of the vesicles. By contrast, enalaprilat, cefadroxil and GlyPro competitively inhibited cephradine transport with Ki values of 5.4, 3.8 and 5.1, respectively. These results suggest the presence of an enalapril-specific inhibitory binding site on the peptide carrier. In addition, enalapril on the trans side (inside) of the vesicles inhibited the uptake of cephradine, suggesting an apparent reduction of carrier availability by a trapping mechanism. On the other hand, cefadroxil stimulated the uptake of cephradine in the trans experiment, consistent with the concept of countertransport. These findings reveal the uniqueness of enalapril regarding its mode of interaction with the peptide carrier(s) which has been of increasing interest regarding its role in the intestinal absorption of peptide-type drugs.

The inhibitory effect of NaCl coadministration on the reabsorption of Li+ in the salivary ducts and the renal tubules was investigated in beagle dogs. Following the bolus intravenous administration of LiCl (0.145 meq/kg), 50 ml of NaCl solution (100, 200 meq/l) was administered orally each hour, and parotid saliva (Pr) and mandibular-sublingual saliva (MS) were collected under the continuous stimulation of salivation with citric acid. The renal clearance of Li+ increased with the increased concentration of administered NaCl solution. This could be a result of the competitive inhibition of the tubular reabsorption of Li+ by Na+. The salivary clearance of Li+ also tended to increase by the administration of NaCl. These results suggest the existence of a reabsorption process of Li+ in the salivary glands similar to that in the renal tubule. However, when the administered NaCl was increased from 100 to 200 meq/l, the renal clearance was further increased, but the salivary clearance was not. This suggests that the transport capacity of Li+ reabsorption is relatively small in the salivary glands, compared with that in the renal tubule, and that the inhibitory effect of NaCl on Li+ reabsorption had already reached a maximum level when 100 meq/l NaCl was administered.

Acute haemodynamic change after single lung transplantation for primary pulmonary hypertension was evaluated using a rat transplantation model. Inbred Fisher 344 rats were administered with 40 mg/kg monocrotaline in order to induce pulmonary hypertension. The rats whose mean pulmonary arterial pressure (PAP) was over 30.0 mm Hg received a left lung isograft from a normal donor after right heart catheterization. In the control group, PAP increased after single lung transplantation. On the other hand, in the pulmonary hypertensive group, PAP was significantly decreased 60 min after the transplantation, but 3 and 6 h after the transplantation, the PAP significantly increased again. On the day after the operation, it again decreased significantly. Left-to-right lung blood flow ratio was significantly increased in rats with pulmonary hypertension compared to rats with normal pulmonary pressure on both the 1st and 3rd postoperative days. The oedema of the grafted lung was more severe in the pulmonary hypertensive group than in the control group in the acute phase. In conclusion, single lung transplantation for pulmonary hypertension shifted pulmonary blood perfusion to the grafted lung and this shift made pulmonary oedema of the grafts more severe in the acute phase. These oedematous changes, which were more pronounced in the grafts in the pulmonary hypertensive rats, might have contributed to the transient rise in PAP in those rats after single lung transplantation.

We have developed the protocol for selective cerebral perfusion (SCP) and pharmacological cerebral protection, and used it successfully in cases of aortic arch aneurysm. The subjects of the present study were 34 patients (28 males, 6 females) whose aortic arch aneurysm were surgically treated. Preoperative brain CT and brain scintigram showed high incidence of brain ischemia. However only 4 patients experienced a neurological episode. We conclude that our SCP technique and pharmacological cerebral protection are useful component to surgery of the aortic arch.

We investigated the hormonal responsiveness of gland and stroma in the male accessory sex organs (ventral prostate, dorsolateral prostate and seminal vesicle). Immature rats (3 weeks old) were castrated and left untreated for 4 weeks and then distributed at random into 3 groups, A, B, C. The rats in groups A, B and C were injected subcutaneously with 0.2 ml of soybean oil, 5 alpha-dihydrotestosterone (DHT, 500 micrograms/day) or estradiol-17 beta (E2-17 beta, 5 micrograms/day), respectively, for 14 days before they were killed. DHT administration in prepuberal castrates stimulated collagen synthesis and accumulation in the stroma of male accessory sex organs as well as the proliferation and differentiation of the glandular epithelium in these organs. In E2-17 beta treated rats, the glandular epithelium of ventral prostate and seminal vesicle had mostly a single layer structure, but the glandular epithelium of dorsolateral prostate had a mostly multilayer structure. On the other hand, in E2-17 beta treated rats, the EMBP content, an indicator of glandular epithelium differentiation in male accessory sex organs, did not increase even in the dorsolateral prostate which showed a multilayer gland epithelium. Collagen synthesis and accumulation in the seminal vesicle was stimulated by E2-17 beta treatment several times as much as in the ventral and dorsolateral prostate. Histological investigation demonstrated that the seminal vesicle in prepuberal castrates treated with E2-17 beta resembled that of fibromuscular type human benign prostatic hyperplasia.

We compared the influence of anesthetic regimens using urethane (U), pentobarbital (P), ether (E), and ketamine/midazolam (K) on the intestinal absorption of several probes using a single-pass perfusion technique in rats. The selected probes were D-glucose (1 mM) for the resistance of the unstirred water layer (UWL), D-glucose (100 mM) for the capacity of carrier-mediated D-glucose transport, L-glucose, and urea for membrane-limited passive transport, and tritiated water (3H2O) for blood flow at the absorption site. The absorbed fraction of D-glucose (1 mM) was the smallest for U and the largest for P, suggesting that the resistance of UWL is the largest for U and the smallest for P. The absorbed fraction of D-glucose (100 mM) was the largest for P (U = E = KP), suggesting a higher capacity of carrier-mediated D-glucose transport for P. The absorbed fraction of urea was similar for all anesthetics, while that of L-glucose was the smallest for K (U = P = EK). Although the results for these two markers of membrane-limited passive transport were inconsistent, the passive permeability of the intestinal membrane may be lower when treating with K. The intestinal absorptions of D-glucose (1 and 100 mM), L-glucose, and urea were, in general, lower with any of the anesthetics than under nonanesthesia (N), suggesting increased resistance of UWL and decreased intestinal membrane permeability by carrier-mediated and passive transport under anesthesia. The only exception was the absorption of D-glucose (100 mM) under P, which was comparable to that under N.(ABSTRACT TRUNCATED AT 250 WORDS)

The uptake kinetics of cephradine, an amino-beta-lactam antibiotic, were studied in rat and rabbit intestinal brush border membrane vesicles preparations using both the Ca2+ and the Mg2+ methods of preparation, in the presence of an inward proton gradient. The Ca2+ method demonstrated greater uptake of cephradine in intestinal brush border vesicles prepared from both rat and rabbit and was used for these studies. The transport was observed to be of Michaelis-Menten carrier-mediated type with a passive transport component. The kinetic parameters obtained were as follows: for rat and rabbit, respectively, Km, 1.6 and 1.9 mM; Jmax', 1.7 and 20.7 nmol/mg/min; Pc' (= Jmax'/Km), 1.1 and 10.9 microL/mg/min; and Pm', 0.4 and 0.8 microL/mg/min. The kinetic parameters for the rat vesicles are consistent with those from our previous perfusion study using a conversion factor of 0.71 cm2/mg protein. The rabbit vesicles exhibited a similar Michaelis constant and a 10-fold larger maximal transport velocity, suggesting a quantitative advantage for the study of carrier-mediated transport in the rabbit compared to rat vesicles from the intestine. Cephradine uptake was inhibited by phenylpropionylproline, a proline derivative, and enalapril, an ACE inhibitor, which do not have an alpha-amino group, as well as dipeptides, tripeptides, and amino-beta-lactam antibiotics in both rat and rabbit vesicles. These results support the suggestion that they share the same peptide carrier pathway for oral absorption and that the vesicles may be a useful tool in developing orally effective peptide-type drugs.

We assessed the histologic changes in donor and recipient bronchi from 15 dogs that had received a lung transplant and related these changes to the severity of acute rejection seen in the parenchyma of these same lungs. Minimal rejection was associated with no abnormal change in either the donor or the recipient bronchi. In mild lung rejection, mononuclear cell cuffings were seen around bronchial arteries in donor bronchial adventitia, although few mononuclear cell infiltrates were seen in the submucosa. Moderate lung rejection was associated with more prominent mononuclear cell cuffings in the donor bronchial adventitia and mucosal infiltrates of mononuclear cells in the membranous portion. In cases of severe lung rejection, the mononuclear cell infiltrates were also apparent in the cartilaginous portion of the donor bronchial mucosa. Moreover, submucosal edema and detachment of bronchial epithelium were seen. These histologic changes were not observed in the recipient bronchi during acute rejection, nor were they seen in the donor and the recipient bronchi during lung infection without rejection. They might, therefore, reflect acute rejection in the donor bronchus. These results might provide the histologic support for our previous observation of decreased bronchial mucosal blood flow measured by the laser Doppler flowmeter in relation with the extent of acute lung rejection.

Eleven patients underwent surgical excision for left atrial myxomas. Clinical symptoms, coronary angiographic findings and operative procedures were evaluated. Myxomas were classified into two types based on macroscopical findings, and clinical characteristics of these two types were analyzed. Seven cases (64%) classified as "lobular-type myxomas" were seen as lobulated, gelatinous and fragile. Four cases (36%) were classified as "round-type myxomas" were round and elastic soft. Primary symptoms included dyspnea on exertion in five cases (45%) and neurological disturbances in six cases (55%). Brain emboli were found in four patients by CT scan, and were classified as lobular-type myxomas. These eleven myxomas successfully removed in all cases. Four of these myxomas, which were pedunculated with fine fibrous stalks, were shaved along the base at the atrial septum or free wall. Others were excised completely along with a portion of the adjacent septum. Microscopic examination of the operative specimens revealed that two lobular-type myxomas with broad-based attachment to left atrial septum had invaded the atrial septum. All patients are doing well and have had no signs of myxoma recurrence at postoperative periods ranging from 10 months to 12 years (mean follow-up 5.3 years). Seven patients underwent selective coronary angiography due to a diagnosis of a coronary artery disease. All coronary angiograms were normal in all cases. In five (71%) of these seven, abnormally dilated atrial branches were seen as supplying the tumor. In two cases with round-type myxomas, neovascularity was evident and was made up of clusters of tortuous vessels with tumor blush.(ABSTRACT TRUNCATED AT 250 WORDS)

A 46-year-old male patient with aneurysm involving the distal arch and the descending aorta was operated on successfully. Graft replacement of aneurysm with inclusion method was performed through median sternotomy with left pleurotomy. One month after operation, CT scan showed thrombus occupied between the graft and the aneurysm, and two years postoperatively, the aneurysm shrunk almost to normal size of the aorta. Therefore, our surgical procedure was considered to be proper.

A human monoclonal antibody (MCA), CLN-IgG, showed cytotoxic effect in vitro against the cervical carcinoma cell line, ME-180, by antibody dependent cell-mediated cytotoxicity (ADCC). To determine which fractions of cells in peripheral blood lymphocyte (PBL) mediate ADCC, PBL were separated with nylon wool column and sheep red blood cells (SRBC). Both adherent cells (monocyte) and non-T, non-B cells showed cytotoxicity by ADCC. Human non-T, non-B cells showed higher cytotoxic activity against ME-180 cells than monocytes. Furthermore murine effector cells were less effective in ADCC than human effector cells with human MCA.

We analyzed the outcome for 18 patients with prosthetic valve endocarditis (PVE) treated between 1965 and 1990, 17 of whom had undergone valve replacement with mechanical prosthetic valves and one of whom had a bioprosthesis. Two patients developed infection within 60 days after surgery, and 16 thereafter. Fifteen patients received combined medical and surgical therapy and three medical therapy. In 14 patients, surgery had been performed during active infection. Mortality rate of those who had received combined medical and surgical therapy was 27%, and that of those who had received medical therapy was 67%. At operation, para-annular abscess was around the mitral prosthesis was found in three patients and around the aortic prosthesis in eight. Seven patients required reoperation for postoperative paravalvular leakage, in six, para-annular abscess had been found at the operation for PVE, and in one para-annular abscess had been noted. One patient who had undergone reoperation had developed reinfection after the first surgery and died due to multiple organ failure after the second operation (Danielson's translocation technique). In one patient who had complete loss of supporting tissue because of severe para-annular abscess, we had performed aortic valve replacement by implanting the aortic valve prosthesis into the left ventricle with Dacron felt-supported sutures placed in the mitral annulus and the muscles of the left ventricular outflow tract. This patient showed no postoperative infection or no paravalvular leakage.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of postpneumonectomy pyothorax due to bronchopleural fistula (BPF) is troublesome, especially with methicillin-resistant staphylococcus aureus (MRSA) infection. Moreover, in a bypass-grafting case, the management becomes more complicated. We reported a successful treated case of MRSA pyothorax due to BPF after grafting and pneumonectomy. In a 48-year-old woman performed grafting and pneumonectomy for traumatic aneurysm of the thoracic aorta, MRSA pyothorax due to BPF occurred. BPF was successfully closed by fibrin-glueing under bronchofiberscopy. However pyothorax was not improved by thoracic irrigation for a month. Therefore, open pleural drainage underwent. At the same time, bronchial stump and graft surface was covered with the omental pedicle flap. The open wound had become sterile in two months, and the thoracic window was closed three months after the open drainage.

A 59-year-old man was admitted to our hospital because of compression fracture of the lumbar spine and pubic bone fracture following fall from a ladder. On admission the only a little left pleural effusion in the thorax was noted. Two days later, x-ray film of the chest revealed massive left pleural effusion. Under the diagnosis of left hemothorax, left thoracotomy was performed. Then we found incidentally that the left pericardium had ruptured longitudinally over the length. Herniation of the heart was not developed. The ruptured pericardium was repaired using Teflon mesh.

Between January 1983 and June 1990, there were 48 patients who underwent surgery for mitral regurgitation due to degenerative diseases. Among these, 20 patients received mitral valve repair. Overall operative mortality was 5% for patients who underwent valve repair, and 7.1% for those who underwent valve replacement. We standardized a maneuver for valve repair in August 1988 in an attempt to expand its indications. There were 35 patients who underwent surgery prior to that date (group 1), and 13 patients after that date (group 2). There were nine patients (25.7%) in group 1 and 2 patients (84.6%) in group 2 who underwent valve repair. Among these, one patient (11%) in group 1 died within 30 days after the operation, but there were no surgical deaths for any patients in group 2. In addition, one patient (11%) in group 1 and one (9%) in group 2 required another operation for valve replacement. Doppler echocardiographic studies performed postoperatively in 18 patients who had undergone valve repair showed that 13 (72.2%) had no regurgitation, 4 (22.2%) had trivial regurgitation, and 1 (5.6%) had mild regurgitation. Postoperative valve area as determined by continuous-wave Doppler echocardiography was 3.7 +/- 1.1 cm2 (mean +/- SD) for patients who had undergone reconstruction and 3.1 +/- 0.7 cm2 for those who had undergone replacement.

Postoperative pulmonary complications cause the decrease of the flow of remaining pulmonary circulation. We examined the effects of the difference of resected lobes on the postoperative course and remaining pulmonary circulation of the lobectomized lung cancer patients using a pulmonary digital subtraction angiography. In all cases with preoperative pulmonary complications, circulatory flow of the remaining lung on the operated side significantly decreased. In the cases without preoperative pulmonary complications, only the cases performed left upper lobectomy developed the decrease of the circulatory flow on the operated side. This seemed to be chiefly caused by a postoperative continual atelectasis of the remaining lower lobe due to kinking of the bronchus. On the other hand, the postoperative decrease of the residual pulmonary circulatory flow on the operated side was not developed in the cases undergoing a segmentectomy, even with pulmonary complications. Therefore, for any case requiring a left upper lobectomy or the case with an impaired lung requiring any type of lobectomy, contralateral pulmonary function should be exactly evaluated preoperatively.

Ten cases of central airway obstruction mainly caused by extrinsic compression due to the growth of extratracheal malignant tumors or longitudinal extension of tracheal adenoid cystic carcinomas, underwent palliative intubation subsequent to endoscopic Nd-YAG laser treatment. Mean length of the severe stenosis in these cases was 4.4 cm (3-7 cm). Sole application of endoscopic Nd-YAG laser to the stenosis failed relief of the symptom and an immediate palliative intubation was recommended. Mean time of the temporary intubation was 7 days (4-11 days). Airway was maintained by this intubation and also retained enough after extubation. Therefore, it seemed that, in a palliative treatment of the central airway severe stenosis, usefulness of the combination management of Nd-YAG laser with following temporary intubation was revealed. However, in order to maintain the airway for recurrence of the obstruction, use of indwelling airway stents seemed a better application. The longest period of follow-up in the cases treated by indwelling airway stents was 6 months and one of the cases is a now in comfortable state.

Bronchial mucosal blood flow (BMBF) was measured with a laser-Doppler flowmeter in a canine model (n = 20), and the measurement was evaluated to see if it was a useful method for diagnosing allografted lung rejection. The ratio of the value of BMBF at the level of the donor second carina against that at the level of carina (the L/C ratio, an index of BMBF of donor bronchus) decreased in accordance with the extent of lung rejection, and it increased and entered the normal range with the reversal of lung rejection. Compared with the L/C ratio and the rejection grade by histologic changes in open-lung biopsy, the L/C ratio at grade 0 (latent phase) was 0.91 +/- 0.07; at grade Ia (early vascular phase), 0.86 +/- 0.05; at grade Ib (late vascular phase), 0.68 +/- 0.10; at grade II (early alveolar phase), 0.60 +/- 0.14; and at grade III (late alveolar phase), 0.50 +/- 0.15. A significant difference was noted between grades Ia and Ib (p less than 0.01) and between grades Ib and III (p less than 0.01). The sensitivity and the specificity in the detection of early rejection before grade Ib were 96% and 92%, with only one false-negative and two false-positives resulting from 51 measurements of BMBF. In three cases of serious lung infections, the L/C ratio did not fall, and the rejection could be distinguished from infection. These results suggest that measurement of the BMBF is useful for detecting the early rejection of transplanted lungs.

We investigated the relationship between the rejection of lung allografts and the bronchial mucosal blood flow with a laser flowmeter. Nineteen mongrel dogs underwent left lung allotransplantation and were given daily oral immunosuppressive therapy with azathioprine and cyclosporine. The bronchial mucosal blood flow at the carina and the bifurcation of left upper and lower bronchi were measured on days 14, 21, and 28 after left lung transplantation. The bronchial mucosal blood flow of the transplanted lungs was expressed as the ratio of bronchial mucosal blood flow at the bifurcation of left upper and lower bronchi to the bronchial mucosal blood flow at the carina (L/C ratio) instead of the absolute value because bronchial mucosal blood flow was affected by the depth of anesthesia of the dogs. We classified the histologic appearance of the transplanted lung tissue into one of five grades: 0, 1a, 1b, 2, and 3. No rejection was in grade 0, and as the rejection process progressed the higher grades were used in order. The mean L/C ratios for grades 0, 1a, 1b, 2, and 3 were 0.95 +/- 0.03, 0.82 +/- 0.05, 0.68 +/- 0.04, 0.58 +/- 0.07, and 0.30 +/- 0.07, respectively. Thus the L/C ratio decreased as the rejection process progressed. The histologic changes of the donor main bronchus in each rejection grade were investigated. Mononuclear cell infiltration and edema around the small vessels was seen in early rejection. These same histologic changes appeared in muscular arteries as rejection progressed, and the damage to the small vessels and muscular arteries was more severe in late rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

We studied surgical results of 14 cases of ischemic mitral regurgitation. There was no surgical death in 10 cases with left ventricular aneurysm, and their clinical symptoms improved except 3 with the combined operation of left ventricular aneurysmectomy, mitral annuloplasty and bypass grafting. The range of the abnormal contracting segment significantly decreased after surgery except in 3 cases in whom clinical status was not improved. Three of 4 cases which underwent bypass grafting and mitral annulo-valvuloplasty survived, but one of them died of graft-versus-host disease. In the three survived cases, severe mitral regurgitation disappeared. We have concluded as follows: In cases of left ventricular aneurysm, a sufficient aneurysmal resection is very important to control the mitral regurgitation, and the additional procedures of mitral annuloplasty and bypass grafting are essential. The mitral valve replacement is recommended in case of the complete disruption of the papillary muscle. Mitral valvuloplasty combined with annuloplasty is suitable to control the regurgitation in the regional mitral prolapse due to the torn chordae.

The hemostatic effect of nafamostat mesilate (FUT-175) was evaluated in patients undergoing cardiopulmonary bypass (CPB) surgery. Thirty patients undergoing aortocoronary bypass grafting were divided into two groups. In the control group, anticoagulation was achieved with an initial dose of heparin (3 mg/kg). In the FUT-175-treated group, in addition to the ordinary treatment with heparin, FUT-175 was infused continuously into the circuit throughout the procedure at a rate of 100 mg/hr. Thrombin-antithrombin III complex (TAT), fibrinopeptide A (FPA), and fibrin degradation products (FDP-D) dimer increased in both groups as CPB proceeded. In the FUT-175-treated group, these parameters remained lower and decreased more rapidly after the end of CPB. Alpha 2 plasmin inhibitor/plasmin complex (PIC) increased progressively during CPB in the control group; no such significant increases were seen in the FUT-175-treated group. Postoperative blood loss was significantly lower in the FUT-175-treated group than in the control group. It was concluded that FUT-175 reduces postoperative blood loss by inhibiting both coagulation and fibrinolysis during CPB.

A study was undertaken to evaluate hemolysis and subsequent renal damage in 14 patients undergoing cardiopulmonary bypass (CPB) surgery. In all patients, free haptoglobin disappeared completely 30 to 90 minutes into CPB, while free hemoglobin (Hb) levels increased progressively. The NAG index and alpha 1M index also increased progressively, indicating renal tubular injury due to hemolysis (Study 1). An additional 20 patients were monitored intraoperatively for plasma free Hb levels by a newly developed colorimetric method using a haptoglobin coated strip. Free Hb levels during CPB exceeded 30 mg/dl in 14 patients, who were immediately given haptoglobin. This treatment eliminated plasma free Hb within 30 minutes, and effectively prevented hemoglobinuria. Haptoglobin treatment brought significant decreases in the NAG index and alpha 1M index, suggesting a protective effect on renal function (Study 2).

New thermo-responsive hydrogels were synthesized by copolymerizing acryloyl-L-proline methyl ester (A-ProOMe) with minor amounts of 2-hydroxypropyl methacrylate (HPMA) or polyethylene glycol 600 dimethacrylate (14G), using gamma-rays from a 60Co source. In water, extensive swelling of the hydrogels occurred at 10 degrees C, but there was marked deswelling as the temperature was raised to 37 degrees C. The poly(A-ProOMe-co-HPMA) hydrogel was characterized by an initial rapid shrinkage at the surface in the deswollen state; this shrinkage arose because of the formation of a rigid membrane barrier devoid of micropores. The system is therefore 'surface regulated'. In contrast, no such a barrier formed in the deswollen poly(A-ProOMe-co-14G) hydrogel. The whole matrix shrunk without the disappearance of micropores, and it is therefore a 'matrix pumping' system. Testosterone was incorporated into both these types of hydrogels, and the drug-loaded hydrogels were implanted subcutaneously into the backs of castrated rats. The daily dose of testosterone released in vivo from the poly(A-ProOMe-co-HPMA) hydrogel was constant at approximately 30 micrograms/day throughout an experimental period of 54 weeks. In contrast, drug release from the poly(A-ProOME-co-14G) hydrogel reached a maximum after one week and then decreased linearly with time down to the 7th week, when it was undetectable. These conclusions were supported by the changes in weight of the ventral prostates and right-side seminal vesicles of the rats, which were restored to normal when delivery of the testosterone was sustained.