OPC-8212, a quinoline derivative, counteracts the reduction in type III collagen mRNA due to lipopolysaccharides in cultured rat cardiac fibroblasts

Fibrillar collagen plays an essential role in ventricular remodeling, which is a major prognostic factor in various heart diseases. Inflammatory cytokines, including tumor necrosis factor alpha (TNFalpha), have been reported to play a role in various heart diseases and OPC-8212, a quinolinone derivative, has been demonstrated to reduce TNFalpha production. No studies have examined the effects of OPC-8212 on collagen metabolism in connection with inflammatory cytokine and growth factors. Using lipopolysaccharides as a tool to enhance TNFalpha, we examined the effects of OPC-8212 on the expression of type III collagen mRNA [alpha1(III)] in cultured neonatal rat cardiac fibroblasts. We also measured the concentration of TNFalpha and transforming growth factor beta (TGFbeta) in the cultured medium. Northern blot analysis revealed that LPS reduced the expression of alpha1(III) mRNA, and OPC-8212 counteracted this reduction (on average 25% above the reduced level by LPS stimulation). LPS enhanced the TNFalpha concentration in the medium, and OPC-8212 inhibited this enhancement. LPS increased the TGF-beta1 concentration in the cultured medium, while OPC-8212 did not affect this increase. In summary, OPC-8212 counteracted the reduction in type III collagen mRNA expression by LPS accompanied by suppression of the increase in TNFalpha.     

Host factors which influence the outcome of pneumonia in the elderly]

We examined 135 elderly patients with pneumonia to clarify the factors predicting on the outcomes of the elderly pneumonic patients. In the fatal cases respiratory symptoms such as cough and sputum, except for dyspnea were less frequent but pulmonary infiltrations on chest roentgenograms were more massive as compared with those in the survived cases. Thus, it was suggested that in the fatal cases the more advanced pneumonia had developed at the time when the diagnosis of pneumonia was made. The fatal cases showed hypoalbuminemia, hypocholesterolemia and hyponatlemia more frequently as compared with survived cases. Among these laboratory values, the decreased serum albumin concentration seemed to be most closely correlated with the fatal outcome of the elderly pneumonic patients. There were significant differences in the outcomes among three groups of the patients, those who were the prolonged bed-ridden, those with severe underlying diseases such as cancer and those treated as out-patients. The out patients showed the most favorable outcome and the prolonged bed-ridden patients the worst outcome. Approximately, 39% of the fatal cases were complicated with multiple organ failure. These results suggest that more important factors which affect the outcomes of pneumonia in the elderly may be not merely aging but the conditions of the host at onset of the disease.     

Small ileal neurofibroma causing intussusception in a non-neurofibromatosis patient

Neurofibromas in the small intestine are usually accompanied by von Recklinghausen's disease (neurofibromatosis), and usually originate in the intramuscular plexus of Auerbach. We present here a solitary neurofibroma, which caused an ileocolic intussusception, originating in the submucosal plexus of Meissner in a non-neurofibromatosis patient. To our knowledge, there is no previous report of a neurofibroma originating in the plexus of Meissner. This condition was clearly confirmed by macroscopic and microscopic evaluation.     

Gore-Tex jump graft for portal vein thrombosis following living donor liver transplantation

Portal vein thrombosis is a rare surgical complication following liver transplantation, which remains a cause of graft loss and death. We describe here the treatment of portal vein thrombosis following living donor liver transplantation using an extended left lobe graft. The patient was treated with a Gore-Tex vascular jump graft extra-anatomically interposed between the recipient superior mesenteric vein and the donor umbilical vein. This technique allowed the hepatic hilum to be left untouched and supplied suitable blood flow to the hepatic allograft. Our experience suggests that this innovative technical solution can be helpful in the effort to rescue cases of hepatic allograft with vascular complications.     

Vaccination with clumping factor A and fibronectin binding protein A to prevent Staphylococcus aureus infection of an aortic patch in mice

Staphylococcus aureus is a leading cause of ventricular assist device-related infections. This study evaluated the protective effect against S. aureus infection of active and passive immunization that targeted 3 proteins involved in bacterial attachment to a murine intra-aortic polyurethane patch. Active immunization of mice with a combination of the A domains of clumping factor A (ClfA), fibronectin-binding protein A (FnBPA) and fibronectin-binding protein B or passive immunization with monoclonal antibodies against ClfA and FnBPA resulted in a higher level of protection than that obtained by vaccination with either protein or antibody alone. The combination of antibodies or protein antigens appears to provide enhanced protection against prosthetic-device infection.     

Immunostimulatory effects of different antilymphocyte globulin preparations: a possible clue to their clinical effect

Antilymphocyte globulin (ALG) and antithymocyte globulin (ATG) have an established role in the treatment of severe aplastic anaemia. The response rate ranges from 40% to 80%. Its mode of action is believed to be complement dependent lysis of immunocompetent cells which inhibit haemopoietic maturation. This might not be the sole mechanism. We have tested four different preparations of ALG/ATG for their mitogenic effect on normal peripheral blood cells and on enriched T-cells in vitro by 3H-thymidine incorporation. We found marked differences between the four preparations. One was strongly mitogenic and able to induce profound release of haemopoietic growth factors. This mitogenic effect could be detected in the serum of patients during ALG treatment. Clinical response rates of this preparation are about 80%. Three other preparations were of lower or no stimulatory effect. Clinical response rates with these preparations vary between 40% and 60%. From our results, we postulate that the beneficial effect of ALG could be partially due to its ability to stimulate release of haemopoietic growth factors. The mitogenicity of different ALG/ATG preparations should be tested as an in vitro parameter of clinical efficacy.     

Evaluation of prognostic score based on the Japanese criteria for the severity of acute pancreatitis. Part I. Retrospective study

We used the Japanese Ministry of Health and Welfare criteria for acute pancreatitis to obtain a “prognosis score” for disease severity in 63 individuals with severe pancreatitis and we assessed the usefulness of these scores. To convert the Japanese criteria into a score, we excluded the CT grade classification, assigned a value of 1 point to the prognostic factors designated , and a value of 0.5 points to the prognostic factors designated , and added the number of points to obtain the “prognosis score”. The results showed a clear difference in prognosis between patients who had scores of 1.5 or less and those whose scores were 2.0 or more. These prognosis scores were useful both in rating the efficacy of treatment and in selecting the method of treatment in the early stage. To confirm the value of these scores, it will be necessary to accumulate more cases prospectively and to conduct additional assessments.     

Liver metastasis of rectal cancer with intraluminal growth in the extrahepatic bile duct

Metastatic liver tumors are considered to have a tendency for expansive growth and rarely invade the bile duct. We recently encountered a resected case of liver metastasis from rectal cancer with intraluminal growth in the extrahepatic bile duct with a successful left trisegmentectomy of the liver. A 54-year-old woman underwent a posterior total pelvic exenteration for advanced rectal cancer. Ultrasonography and computed tomography four months after the first operation demonstrated a solitary occupied lesion in the liver with dilation of the left hepatic duct. Endoscopic retrograde cholangiopancreatography disclosed a filling defect in the intra- to extrahepatic bile duct. Liver metastasis from rectal cancer with intraluminal growth in the bile duct was suspected despite a consideration of primary bile duct cancer. A left trisegmentectomy of the liver and resection of the extrahepatic bile duct with a right hepatojejunostomy were performed. The tumor had invaded the intrahepatic bile duct and had developed intraluminally in the extrahepatic bile duct. Tumor thrombi were microscopically found in the bile duct of the left caudal lobe. Liver metastasis arising from colorectal cancer with intraluminal growth in the bile duct is rare, however we encountered such a case with a successful resection involving a left trisegmentectomy of the liver.     

R353Q polymorphism, activated factor VII, and risk of premature myocardial infarction in Japanese men.

BACKGROUND: The association between myocardial infarction (MI) and the R353Q polymorphism of the Factor VII (FVII) gene, which reportedly influences FVII concentrations, activated Factor VII (FVIIa), or FVII antigen (FVIIag), remains controversial. METHODS AND RESULTS: The present case - control study in 127 Japanese men with their first MI at or before 45 years of age and 150 matched healthy controls was designed to clarify this association in premature MI. R353Q polymorphism was determined by polymerase chain reaction, and plasma concentrations of FVIIa and FVIIag were assayed. The distribution of the RR, RQ, and QQ genotypes with respect to R353Q polymorphism was 117, 10, and 0 in the patients, and 131, 17, and 2 in the controls. The Q allele was negatively associated with premature MI (odds ratio =0.41, p=0.038). The plasma concentration of FVIIa was slightly higher in patients (55.1+/-40.9 U/L) than in controls (44.8+/-20.2 U/L), but not significantly (p=0.078); the plasma concentration of FVIIag did not differ between patients (88.7+/-15.7%) and controls (87.0+/-9.0%) (p=0.557). Plasma FVIIa concentrations were influenced by R353Q polymorphism (p<0.001). CONCLUSIONS: The Q allele may be protective against premature MI.     

Immediate and chronic results of cutting balloon angioplasty: A matched comparison with conventional angioplasty

Background: At the initial stages of percutaneous transluminal coronary angioplasty (PTCA), several studies reported on the feasibility of coronary artery incision and dilatation leading to the extension of the PTCA technique. Hypothesis: This study was designed to determine the immediate and chronic results of cutting balloon (CB) angioplasty. Methods: This procedure was performed on 127 lesions in 110 patients (male 83%, age 61.8 ± 9.3 years). Results: The overall procedural success rates for the CB were 93.7% (119 lesions) and 92.7% (102 patients), while solitary CB without pre- and/or postdilatation was 76.4% (91 lesions). There was one major in-hospital complication (Q-wave myocardial infarction, 0.9%), but there were no deaths or emergency coronary artery bypass graftings. Significant angiographic dissections (≥ grade C) occurred in four patients, and coronary perforation occurred in one. The successfully treated CB group (95 lesions) was matched with the successful conventional angioplasty group (PTCA group) for chronic result assessment in regard to reference vessel size and lesion characteristics. In the CB group, postprocedural minimal luminal diameters were significantly larger and the percentage of stenosis at the stenotic site was significantly lower compared with the PTCA group. Restenosis occurred in 22 lesions (23.1%). This showed a significantly lower restenosis rate compared with the PTCA group (42.1%). In addition, the restenosis rate of the CB without inclusion of the pre- and/or postdilatation-treated lesions was 19.7%. Conclusions: (1) Cutting balloon angioplasty procedures can be performed with high success rates with few major in-hospital events. (2) The restenosis rate in the CB group was significantly lower compared with the PTCA group.