[Reoperation through right thoracotomy for mitral regurgitation after coronary artery bypass grafting; report of a case].

A 53-year-old male patient developed severe mitral regurgitation 6 years after coronary artery bypass grafting (CABG) with a left internal thoracic artery and 2 saphenous veins. The left ventriculography showed severe mitral regurgitation and slight decrease in left ventricular function. The coronary arteriography showed all grafts being patent. The median re-sternotomy was avoided because of the risk for injury of bypass grafts, and the right anterolateral thoracotomy was chosen. Mitral valve replacement was performed under moderate hypothermia and ventricular fibrillation without aortic cross clamping. The postoperative course was uneventful. Right anterolateral thoracotomy is considered to be a superior approach to the mitral valve surgery in the patients with previous CABG.

Influences of nonpulsatile pulmonary flow on pulmonary function. Evaluation in a chronic animal model.

To clarify the influences of nonpulsatile blood flow on the physiologic function of the lung, we established nonpulsatile pulmonary circulation with a centrifugal pump in a chronic animal model (adult goats, n = 6). As the initial phase, a pulsatile right ventricular assist device was implanted to bypass the whole blood supply from both the right atrium and right ventricle to the pulmonary artery. After 2 weeks of pumping, the pulsatile pump was replaced with a centrifugal pump without anesthesia, and nonpulsatile pulmonary circulation was instituted. In this experimental model, no significant change was observed in either mean pulmonary arterial pressure or pulmonary vascular resistance index during the pulsatile pumping compared with that on the fourteenth day of nonpulsatile pumping. Blood gas data, extravascular lung water content, and serum level of angiotensin-converting enzyme were maintained within normal ranges. There was also no significant change in the ventral to dorsal blood perfusion ratio of the lower lobe of the right lung. These results indicate that pulmonary functions are not affected by nonpulsatile pulmonary circulation for a period of 14 days in this animal model.

Vasitis nodosa: immunohistochemical findings--case report.

We report the immunohistochemical features of vasitis nodosa and discuss the differential diagnosis. The patient was a 42-year-old Japanese man with bilateral small indurations of the vas deferens at the site of a previous vasectomy. Microscopically, small-sized ducts proliferated within the muscular wall of the vas deferens, and focally in the surrounding connective tissue. Immunohistochemically, most proliferating glandular cells were strongly positive for cytokeratins 7, 19, and 34betaE12, and vimentin. Epithelial membrane antigen and Leu-M1 reacted against the luminal surface of the cells. Focally, glandular cells were also positive for CA125. Cytokeratin 20, carcinoembryonic antigen, and prostate-specific antigen were negative. We discuss the immunohistochemical differentiation of vasitis nodosa from prostatic adenocarcinoma, adenocarcinoma of the rete testis, and adenomatoid tumor.

Interaction between emerin and nuclear lamins.

Emerin is an inner nuclear membrane protein that is involved in X-linked recessive Emery-Dreifuss muscular dystrophy (X-EDMD). Although the function of this protein is still unknown, we revealed that C-terminus transmembrane domain-truncated emerin (amino acid 1-225) binds to lamin A with higher affinity than lamin C. Screening for the emerin binding protein and immunoprecipitation analysis showed that lamin A binds to emerin specifically. We also used the yeast two-hybrid system to clarify that this interaction requires the top half of the tail domain (amino acid 384-566) of lamin A. Lamin A and lamin C are alternative splicing products of the lamin A/C gene that is responsible for autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD). These results indicate that the emerin-lamin interaction requires the tail domains of lamin A and lamin C. The data also suggest that the lamin A-specific region (amino acids 567-664) plays some indirect role in the difference in emerin-binding capacity between lamin A and lamin C. This is the first report that refers the difference between lamin A and lamin C in the interaction with emerin. These data also suggest that lamin A is important for nuclear membrane integrity.

Prognostic factors in cirrhotic patients receiving long-term sclerotherapy for the first bleeding from oesophageal varices.

OBJECTIVE AND DESIGN: The aim of this study was to identify prognostic factors in cirrhotic patients receiving long-term sclerotherapy for their first bleeding from oesophageal varices. METHODS: Ninety-eight patients with acute bleeding from oesophageal varices receiving long-term endoscopic injection sclerotherapy were retrospectively investigated. Thirteen variables (five qualitative and eight quantitative) related to clinical, biological, and radiographic features were collected at admission. The qualitative variables were: gender, hepatocellular carcinoma, cause of cirrhosis, ascites and degree of encephalopathy. The quantitative variables were age, bilirubin, albumin, prothrombin index, number of sessions of sclerotherapy, volume of ethanolamine oleate, time taken to reach the hospital and shock index. These variables were examined with a multivariate analysis using stepwise logistic regression procedures and a prognostic index was calculated from the Cox equation. The predictive power of the final Cox model was prospectively tested in 43 patients with cirrhosis receiving long-term sclerotherapy for their first variceal bleeding. RESULTS: Of the 13 variables studied in a multivariate analysis using a logistic regression model, four had an independent prognostic value: the presence of hepatocellular carcinoma, bilirubin, albumin and time taken to reach the hospital. When the Cox model was examined in an independent set of 43 patients, there were no statistically significant differences between the observed and expected survival. CONCLUSION: Prognosis of patients with bleeding from oesophageal varices is related to residual liver function and time taken to reach the hospital. Furthermore, the presence of hepatocellular carcinoma is an additional risk factor.

Ovarian fibrothecoma with massive edema.

We report a rare case of ovarian fibrothecoma with massive edema. The patient was a 59-year-old woman with a left ovarian mass measuring 11 x 10 x 7 cm. Magnetic resonance images revealed a solid mass showing unhomogeneous content with predominantly high signal intensity on T2-weighted image. Microscopically, the ovarian mass was composed of a cellular area and an edematous hypocellular area. The latter accounted for more than 75% of the tumor. In the cellular area, spindle-shaped or plump tumor cells were randomly distributed or arranged in a fascicular fashion. These cells contained abundant intracytoplasmic lipid. There was dense collagenous connective tissue in the stroma of the cellular areas. In contrast, in the edematous areas spindle or stellate cells were scattered. Alcian blue stain revealed only a small amount of stromal mucin even in the edematous areas. The microscopic findings were consistent with that of fibrothecoma with massive edema. The present case must be differentiated from massive edema of the ovary and sclerosing stromal tumor of the ovary. Immunohistochemistry was not helpful in distinguishing them. The age of the patient and careful histologic observation are important.

Genotypic diversity of Salmonella Enteritidis isolates from sporadic patients in limited area during one year.

OBJECTIVES: Our aims were to investigate the genetic epidemiology of Salmonella enterica serovar Enteritidis (S. Enteritidis) isolates using computerized analysis of restriction enzyme cleavage patterns. METHODS: A total of 106 S. Enteritidis isolates which were collected in Hiroshima Prefecture, Japan in 2001 were tested by pulsed-field gel electrophoresis (PFGE) using BlnI and XbaI enzymes. PFGE profiles were analysed and compared by using Fingerprinting II software. RESULTS: BlnI PFGE analysis divided the isolates into 29 genotypes. At 90% similarity, BlnI cleavage grouped the isolates into 15 genotypes, while XbaI cleavage grouped them into only four. Two major clusters, each with a predominant genotype, were identified by BlnI cleavage at 42% similarity. In spite of the mixed circulation of the two predominant genotypes, one genotype for which a number of subtypes were detected was predominant during the first half of the year. In contrast, the other genotype, for which no variant subtypes were detected, followed during the latter half. The genotypes identified by computerized analysis matched well with those judged by visual inspection. CONCLUSIONS: The results confirmed the usefulness of PFGE performed with BlnI and of the Fingerprinting II software for the genotyping of S. Enteritidis. We think that the prevalent characteristics of the predominant genotypes detected here were related to the genetic variations of S. Enteritidis.

Portal vein hemodynamics in cirrhotic patients with portal hypertensive gastropathy: an echo-Doppler study.

Portal hypertensive gastropathy is a major complication of cirrhosis. The aims of this study were to characterize portal vein hemodynamics and sympathetic nervous activity in cirrhotic patients with gastropathy. Forty-seven cirrhotics (mild gastropathy in 7) and 25 controls were included in this study. Portal vein hemodynamics was assessed by echo-Doppler, and sympathetic nervous activity by plasma adrenaline and noradrenaline concentrations. Portal blood flow was similar in cirrhotics and controls. However, the congestion index of the portal vein (calculated as the ratio of cross-sectional area and blood velocity) was significantly higher in the former than in the latter. Furthermore, the congestion index of the portal vein paralleled the severity of the gastropathy (ANOVA, p < 0.05). Plasma adrenaline and noradrenaline concentrations were higher in cirrhotics than in controls. However, there was no linear relationship between plasma adrenaline (ANOVA, NS) and noradrenaline (ANOVA, NS) concentrations and the severity of gastropathy. These results suggest a relative contribution of "passive congestion" in the pathogenesis of gastropathy.

An implantable left ventricular assist system with an electrical impedance monitoring and control system.

The authors developed an implantable left ventricular assist system (LVAS) for bridge to transplant of rather small sized adults. The pump was made of segmented polyether polyurethane and was 86 mm in diameter, 50 mm in height, with a 70 ml nominal stroke volume. A percutaneous drive line was connected with an external pneumatic control drive unit (CDU). In chronic animal experiments using 11 adult goats, the pump was installed between the LV apex and the descending aorta and was placed in the abdominal wall. Five goats were killed after 4 to 14 weeks while in good physical condition, and one is ongoing. There were no prominent thromboembolic symptoms despite no anti-thrombogenic agent being used. The new electrical impedance-based monitoring and control system (Z system) was installed in the CDU. In this Z system, automatic calibration was performed periodically for several seconds while the drive condition was changed to ensure full-fill of the blood pump. The full-fill to full-empty drive was well controlled by this Z system. In conclusion, the new Z system is practical and useful for monitoring and control of an implantable pump, giving this LVAS a promising place in clinical use.

A bioartificial ventricle used as a totally implantable circulatory assist device.

The authors designed a totally implantable circulatory assist device consisting of a bioartificial ventricle composed of a skeletal muscle ventricle lined with a bioartificial endocardium. The bioartificial endocardium consists of a structural matrix made of a polyurethane porous membrane, fragmented blood vessels, and collagen gel. The authors prepared the polyurethane porous membrane by solvent cocasting with salt powder. They used collagen gel with fragmented goat carotid vein to perform in vitro construction of the bioartificial endocardium. For in vivo construction of the bioartificial endocardium, the authors used a modified version of the tissue fragment method for vascular prostheses. The authors prepared suspensions of tissue fragments using collagen gel with fragmented goat carotid artery. They used a highly porous fabric vascular prosthesis as a structural matrix; tissue fragments were entrapped on the outer surface of the prosthesis, and the prosthesis then was implanted into the carotid artery of four adult goats. In specimens 1 and 3 months postimplantation, cells from the fragmented tissue regenerated an endothelium-like monolayer sheet on the inner surface of the prostheses. Output of a prototype bioartificial ventricle reached 660 ml/min at an afterload of 60 mmHg and a preload of 20 mmHg. Based on these data, the authors conclude that the bioartificial ventricle is promising as an implantable device with excellent antithrombogenicity.

Pulmonary function in a non-pulsatile pulmonary circulation.

The authors suggested that a mammal immediately accommodates well to nonpulsatile flow in the systemic circulation. In the current study, nonpulsatile pulmonary blood flow using a centrifugal pump was established in chronic models to analyze its influence on the pulmonary circulation. A pulsatile right ventricular assist device (RVAD) was implanted to draw blood from both the right atrium and ventricle and send blood to the pulmonary artery in six goats. After 2 weeks, the pulsatile pump was quickly replaced with a centrifugal pump without anesthesia, and a 100% non-pulsatile pulmonary blood flow was obtained. Cardiac output was kept at 80-120 ml/kg/min during the experiments. No changes were observed in hemodynamic parameters, including pulmonary arterial pressure, pulmonary vascular resistance index, and blood gas data, after the immediate depulsation of the pulmonary blood flow. There was also no significant change in the ventral to dorsal tissue blood flow ratio of the lower lobe of the right lung, which was calculated by a colored microsphere method, between pulsatile and non-pulsatile pulmonary blood perfusion. These results suggest that pulmonary function, including blood flow distribution, is not affected by non-pulsatile pulmonary circulation for periods up to 14 days.

Permeation of silicone oil through a diaphragm in an electrohydraulic ventricular assist system.

This study was designed to investigate the permeation of silicone oil through a pump diaphragm made of Pellethane in the authors' electrohydraulic ventricular assist system (EHVAS) and to evaluate influences on organ function. The permeability of the diaphragm to silicone oil was investigated by in vitro experiments. Influences on organ function were evaluated in five goats with an EHVAS by monitoring serum silicon levels (SSi), blood chemical parameters, and histologic findings. Elevation of silicone oil levels in Pellethane sheets immersed in silicone oil demonstrated that the Pellethane diaphragm was, in fact, permeable to silicone oil. The permeation rate of silicone oil was calculated to be 1.75 ml/year in the authors' EHVAS from the data of a diffusion apparatus test. Serum silicon levels did not increase during the EHVAS pumping, and renal and hepatic function were not affected. No abnormality or deposit suggestive of silicone oil was observed. However, the problem of permeation of silicone oil through the pump diaphragm must be solved to allow for a circulatory assist device for long-term use.

Influence of an impeller centrifugal pump on blood components in chronic animal experiments.

A chronic animal experiment was designed to examine the changes in blood components induced by the use of a centrifugal pump (CP). In the pump, an impeller spins in a blood chamber by magnetic coupling with a rotating magnet outside the blood chamber. A pulsatile ventricular assist device was implanted between the left atrium and the descending aorta in four goats weighing from 63 to 75 kg; the CP was installed to replace the assist device, without surgery and anesthesia, more than 2 weeks later when the influences of implantation surgery were diminished. Antithrombotic therapy was performed with oral administration of an antiplatelet agent, cilostazol, a cyclic adenosine monophosphate phosphodiesterase at a dose of 30 mg/kg/day. No significant differences were observed in any of the following parameters: 1) hematocrit, 2) plasma free hemoglobin, 3) lactic acid dehydrogenase, 4) adenosine diphosphate, 5) platelet count, 6) fibrinogen, and 7) antithrombin III, between the data before and after the use of the CP, nor were deformation or pseudopods of platelets seen. The CP developed in the authors' institute and evaluated in this study did not damage blood components, and it proved to be a promising device for long-term use.

An abdominally placed, implantable left ventricular assist system for long-term use.

An implantable left ventricular assist system was developed for long-term use. The system includes an implantable blood pump, a portable control drive unit (CDU), and a monitoring system. The blood pump was designed to be positioned in the left abdominal wall and was made of segmented polyether polyurethane. A percutaneous drive line connected it to the external CDU. The CDU included a continuous pump performance monitoring system that measured electrical impedance between the two metal connectors of a blood pump. In animal experiments using six adult goats, the pump was installed between the left ventricular apex and the descending aorta, and it was placed in the abdominal wall. No antithrombogenic agents were administered during the course of the experiment. This LVAS was easy to use and provided stable hemodynamic conditions for > 8 weeks. Pump output (Op), estimated by impedance, was linearly related to Op measured with an electromagnetic flowmeter. Pump performance was effectively estimated, and the fill-empty drive was well controlled by impedance. There were no significant abnormal hematologic or blood chemistry values, no signs of infection around the pump pocket (except in one animal), and no obvious thromboembolic symptoms. Maximum flow was 6.7 L/min with use of a prototype portable CDU (dimensions, 500 x 168 x 435 mm; weight, 16 kg). In conclusion, this LVAS is promising for long-term clinical use.

[Serotypes and antibiotic sensitivity of hemolytic streptococci isolated from clinical specimens in Hiroshima Prefecture, 1987-1989].

The grouping, the typing and the drug-sensibility of hemolytic streptococci isolated from the clinical specimens taken from 4 medical centers in Hiroshima Prefecture have been examined and reviewed during the past 3 years 1987-1989. The results were summarized in this report. 1. Of 1572 strains of hemolytic streptococci, 844 strains (53.7%) were group A; 539 strains (34.3%), group B; 14 strains (0.9%), group C; 82 strains (5.2%), group G; and 93 strains (5.9%), the others. We found that group A and group B were predominant, and the incidence rate of group B was higher than it used to be. 2. The prevalent types were T-4 (37.9%), T-1 (13.6%), T-12 (12.0%), and T-28 (10.7%) in group A, while Ia (26.2%), M9 (provisional type 18.4%), and III (14.5%) in group B. 3. As far as the detection data of each month is concluded, during the summer season we could hardly detect group A which peak of occurrence during the winter season. These findings were really consistent with the occurrence pattern of those patients who suffered from streptococcal infectious disease. But this occurrence pattern couldn't be found in group B. 4. In our study, the positive frequency was throat swab greater than urine greater than sputum greater than vaginal swab greater than pus greater than ear secretion in order. Group A was mainly isolated from throat swab, while group B, from several specimens including urine. 5. We found that there was a high drug-sensibility to the beta-lactam drugs in all strains except for 3 strains of group B which were resistant to CEX.(ABSTRACT TRUNCATED AT 250 WORDS)

HLA-DR8 subtyping by polymerase chain reaction (PCR)-DNA conformation polymorphism (DCP) analysis: a simple and practical genotyping method.

Two hundred Japanese panels were serologically typed for human leukocyte antigen (HLA) - DR to assign 65 HLA-DR8 haplotypes, which were then subdivided into two genotypes, i.e., DRB1*0802 and DRB1*0803, by a polymerase chain reaction (PCR)--based, simple, and practical method. The panels possessing DR8 specificity were firstly subjected to PCR with a couple of primers specifically to amplify their DR52 associated group--DRB1 genes. PCR products were then denatured in the presence of formamide, electrophoresed in a non-denaturing polyacrylamide gel, and visualized by silver staining. The same DRB1 products of these samples were also mixed with the DRB1*1302, and simultaneously analyzed by the same procedure. Electrophoretic mobilities of the samples were compared with those of the typing standards to genotype their DR8--DRB1 alleles by using the characteristic polymorphism in the single-stranded DNAs and the heteroduplexes. This method, designated PCR--DNA conformation polymorphism (DCP) analysis, allowed for genotyping of the DR8-DRB1 alleles without using sequence-specific oligonucleotide probes (SSOP) or restriction endonucleases. The entire process after PCR was completed within a few hours. The tested panels were also genotyped for DRB1 gene by the PCR-SSOP method for comparison with results obtained by the PCR-DCP method. Satisfactory coincidence was achieved and it represented how accurately the new system genotyped DRB1*0802 and DRB1*0803. PCR-DCP analysis was thus shown to be practical and useful for subtyping of serologically defined DR8 specificities.

[Chromosomal changes in cancers].

In addition to the chromosome changes common to cancers, recent development of cytogenetics in human cancers has revealed, the site of specific chromosome changes which characterize specific cancers. Such cancer-specific aberrations are generally reciprocal translocations or deletions, and in some cases the translocations have been unequivocally demonstrated to involve cellular oncogenes (c-onc) in the new transcriptional control of other genes. Chromosome changes relatively common to cancers are amplification of specific genes by chromosome duplication or selective amplification as manifested by double minutes or homogeneously staining regions, and genome reorganization by nondisjunction, somatic recombination, polyploidization-segregation or other parasexual recombinations. The importance of such genome reorganization in cancer development was discussed in relation to the possible involvement of cellular escape mechanisms.

Effects of interferon-α-transduced tumor cell vaccines and blockade of programmed cell death-1 on the growth of established tumors.

Interferon-alpha (IFN-α) has strong antitumor effects, and IFN-α gene therapy has been used clinically against some cancers. In this study, we evaluated the efficacy of the combination of IFN-α-transduced tumor cell vaccines and programmed cell death 1 (PD-1) blockade, and investigated the mechanisms of the antitumor effects of the combined therapy. A poorly immunogenic murine colorectal cancer cell line, MC38, was transduced to overexpress IFN-α. In a therapeutic model, parental tumor-bearing mice were inoculated with MC38-IFNα cells and an anti-PD-1 antagonistic antibody. Analyses of immunohistochemistry and tumor-specific lysis were performed. The outgrowth of the established tumors was significantly reduced in mice treated with the combination of IFN-α and anti-PD-1. Immunohistochemical analyses of the therapeutic model showed marked infiltration of CD4(+) cells and CD8(+) cells in the established MC38 tumors of mice treated with both IFN-α and anti-PD-1. Significant tumor-specific cytolysis was detected when splenocytes of mice that were treated with both IFN-α and anti-PD-1 were used as effector cells. These results suggest that blockade of the PD-1 PD-ligand enhanced the Th1-type antitumor immune responses induced by IFN-α. The combination of IFN-α gene-transduced tumor cell vaccines and PD-1 blockade may be a possible candidate for a cancer vaccine for clinical trials.

A field isolate of Sendai virus: its high virulence to mice and genetic divergence form prototype strains.

A field isolate of Sendai virus, the Hamamatsu strain, was far more virulent in mice than the prototype Z strain. The Hamamatsu strain replicated more efficiently in the mouse lung than the Z strain, causing deteriorating lung lesions. Nucleotide sequence analysis of the HN, F and M genes revealed that the Hamamatsu strain was divergent from the prototype Z, Harris and Fushimi strains.

Observer agreement and variability in measuring gastric mucosal blood flow by laser Doppler flowmetry in humans.

We evaluated the reliability (i.e. reproducibility and variability) in measuring regional gastric mucosal blood flow by laser Doppler flowmetry in a total of 32 subjects (12 normal subjects and 20 patients with cirrhosis). The measurements were performed in quadruplicate within 10 min by observer A (A1, A2) and B (B1, B2) using blind techniques. The intraclass correlation coefficient (Ri) was used to assess observer agreement. Overall, the level of intra- (Ri, 0.87 for A1 vs. A2 and 0.87 for B1 vs. B2) and interobserver agreement (0.86 for A vs. B) was excellent. In contrast, there was a higher observer variability assessed by coefficient of variation. Overall, the mean value of coefficient of variation was 12% (max. 35%) for A1 vs. A2, 12% (max. 35%) for B1 vs. B2, and 13% (max. 33%) for A vs. B. These results suggest that laser Doppler flowmetry, although the reproducibility may be clinically acceptable, seems to still be a subjective method for quantitation of gastric mucosal blood flow in humans. Therefore, studies using this method can only be acceptable when the changes that investigators intend to measure are significantly higher than the variability.