Does off-pump coronary artery bypass grafting really preserve renal function?

It is well known that the use of cardiopulmonary bypass (CPB) influences renal function and occasionally results in renal failure following cardiac surgery. Coronary artery bypass grafting (CABG) without CPB may avoid this and preserve the perioperative renal function. The present study enrolled 52 patients undergoing CABG without CPB (OPCAB group) and matched them for renal function and prognostic variables with 53 patients undergoing conventional CABG (CABG group). Perioperative renal function and early clinical results were assessed. The OPCAB group had significantly less increase in creatinine levels (0.16 +/- 0.05 vs 0.45 +/- 0.06 mg/dl; p = 0.01) and greater creatinine clearance (81.6 +/- 7.3 vs 56.3 +/- 4.8ml/min; p = 0.01) postoperatively. Postoperative recovery of free water clearance was more prompt in the OPCAB group. The duration of intubation and intensive care unit stay was significantly shorter, and the creatine kinase-MB release and blood transfusion requirements were significantly less in the OPCAB group. The OPCAB technique preserved glomerular filtration rate and prevented the increase in creatinine levels. The results suggest that the technique enables earlier patient recovery and gives superior renal protection compared with conventional CABG.     

Clinical evaluation of anti-aminoacyl tRNA synthetase antibodies in Japanese patients with dermatomyositis

OBJECTIVE: To investigate the distribution of anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies among patients with autoimmune diseases, and to analyze the clinical features of patients with dermatomyositis (DM) with anti-ARS antibodies. METHODS: Serum samples from 315 patients with autoimmune diseases or related disorders who had visited Kanazawa University Hospital or affiliated facilities were assessed for anti-ARS antibodies by immunoprecipitation. In particular, the association between anti-ARS antibodies and clinical features was investigated in detail in patients with DM. RESULTS: Anti-ARS antibody was positive in 16 (29%) of 55 patients with DM, 2 (22%) of 9 patients with polymyositis, and 7 (25%) of 28 patients with idiopathic pulmonary fibrosis. Although anti-ARS antibody was detected with high frequency (63%, 15/24) in DM patients with interstitital lung disease (ILD), the incidence of anti-ARS antibody was very low (3%, 1/31) in DM patients without ILD. Anti-ARS antibody-positive patients with DM had significantly higher incidences of ILD (94% vs 23%) and fever (64% vs 10%) than the antibody-negative patients. Some immunosuppressive agents, in addition to oral corticosteroids, were required more frequently in the antibody-positive patients with DM than the antibody-negative patients (88% vs 26%). Although 60% of DM patients with ILD simultaneously developed ILD and myositis, ILD preceded myositis in 33% of patients. CONCLUSION: Among patients with DM, anti-ARS antibodies are found in a subset with ILD. DM patients with anti-ARS antibodies appear to have a more persistent disease course that requires additional therapy compared to those without anti-ARS antibodies.     

Surgical treatment of prosthetic valve endocarditis with left ventricular-aortic discontinuity: reconstruction of the left ventricular outflow tract with a xenopericardial conduit

BACKGROUND AND AIM OF THE STUDY: Aortic prosthetic valve endocarditis (PVE) with annular destruction presents a challenge that requires techniques to eradicate the infection and correct the hemodynamic abnormality. METHODS: Between July 1, 1996 and March 31, 2000, six patients with native or PVE of the aortic valve and aortic annular destruction underwent surgical treatment. Of these patients, three (two men, one woman; mean age 71.0 years) had circumferential annular destruction of the aortic annulus, and formed the basis of this study. The microorganisms responsible for the infection were Streptococcus spp. in two patients and Staphylococcus aureus in one patient. In addition to aggressive debridement of the infected tissue, repair was achieved by reconstruction of the left ventricular outflow tract with a xenopericardial conduit and fixation of the new prosthetic valve to the conduit. RESULTS: One patient with ventricular septal perforation, multiple systemic embolism and sepsis died of low cardiac output syndrome soon after surgery. Two operative survivors were followed up for 9 and 51 months, with no late deaths. No patient has experienced recurrent infection, pericardial patch aneurysm, or prosthetic valve detachment. CONCLUSION: These operative procedures provide easy and secure fixation of the pericardial patch to the healthy tissue under excellent operative view, as well as a sturdy structure for the fixation of the new prosthesis, and complete exclusion of the abscess cavity from the blood stream.     

A possible role for the loss of CD27-CD70 interaction in myelomagenesis

CD27 is a marker of memory B cells and its interaction with its ligand, CD70, is very important for differentiation into plasma cells. Although CD27 is detected on normal plasma cells, its expression is significantly reduced with the progression of multiple myeloma (MM), including monoclonal gammopathy of undetermined significance (MGUS). CD27+ myeloma cells are thought to represent an early phase of myeloma, as CD27+ plasma cells from MM patients were found to be composed of normal plasma cells (CD19+/CD38++) and myeloma cells (CD19-/CD38++), and monoclonality was detected in the CD27+/CD38++ fraction. Given that the lack of CD27 on plasma cells is related to myelomagenesis and that the pro-apoptotic protein Siva is thought to bind to the cytoplasmic tail of CD27, we analysed alterations of cell growth and genes caused by co-culturing CD27-transfected myeloma cell lines (U266, KMS-5) with CD70-transfected NIH3T3 cells. CD27-CD70 interaction could not induce apoptosis in either type of myeloma transfectant, and binding between Siva and CD27 was not detected. cDNA microarray (human apoptosis CHIP) analysis showed a significant upregulation of expression of the ectodermal neural cortex 1 (ENC1) gene by CD27-CD70 interaction compared with CD27 transfection alone. These findings show that the relationship between the loss of CD27 and oncogenesis of plasma cells is not simple. It remains unclear whether the lack of CD27 leads to evasion of apoptosis.     

Ramatroban (BAY u 3405): A Novel Dual Antagonist of TXA2 Receptor and CRTh2, a Newly Identified Prostaglandin D2 Receptor

It is known that thromboxane A₂ (TXA₂) contributes to various diseases such as bronchial asthma, ischemic heart disease, cerebrovascular disorders and allergic rhinitis. A number of TXA₂ synthase inhibitors and TXA₂ receptor (TP receptor) antagonists have been developed to treat these diseases. Ramatroban (BAY u 3405) was developed as a potent TP receptor antagonist with excellent efficacy against allergic rhinitis in many animal models and patients. Recent studies also revealed that ramatroban can block the newly identified PGD₂ receptor, chemoattractant receptor‐homologous molecule expressed on Th2 cells (CRTh2). PGD₂ induces migration and degranulation of eosinophils through CRTh2 and contributes to late‐phase inflammation and cell damage. Accordingly, it was considered that ramatroban suppresses the late‐phase inflammation via TP receptor and CRTh2 blockade. In terms of the efficacy on vascular systems, it was revealed that ramatroban can suppress the expression of monocyte chemoattractant protein‐1 (MCP‐1) and adhesion molecules in endothelial cells and prevent exacerbation of inflammation by blocking these responses. According to our recent studies in hypercholesterolemic rabbits ramatroban prevents macrophage infiltration through MCP‐1 downregulation and neointimal formation after balloon injury and attenuates vascular response to acetylcholine. Therefore, ramatroban may be beneficial in the treatment of atherosclerosis.     

A very elderly case of advanced gastric cancer with disseminated carcinomatosis of bone marrow and multiple bone metastasis, diagnosed by extremely elevated serum alkaline phosphatase levels, and treated with low-dose S-1 to avoid disseminated intravascular coagulation

We report an 87-year-old woman who was admitted to our hospital due to anemia and extremely elevated serum alkaline phosphatase (ALP) levels. We diagnosed advanced gastric cancer with disseminated carcinomatosis of the bone marrow and multiple bone metastasis. She was immediately treated with low-dose S-1 (50mg/body, p.o., days 1-14) and zoledronic acid hydrate (4mg/body, i.v., day 1) to avoid disseminated intravascular coagulation (DIC). After 1 course of the treatment, she could completely avoid DIC and we found the primary lesion and the metastasis had decreased. Now she is an outpatient and continues treatment without relapse for about 6 months. We consider low-dose S-1 and zoledronic acid hydrate combination therapy to be an effective strategy against advanced gastric cancer with disseminated carcinomatosis of the bone marrow and multiple bone metastasis in very elderly cases.     

Whole-heart dipyridamole stress first-pass myocardial perfusion MRI for the detection of coronary artery disease

A whole-heart coverage MRI sequence, which employes a hybrid of fast gradient echo and echo planar acquisition imaging (FastCard EchoTrain), has recently been developed. Using this sequence, a first-pass myocardial perfusion MRI was shown to be a good noninvasive modality for detecting coronary artery disease (CAD) in a clinical setting. In addition, the clinical usefulness of delayed enhanced MRI has recently been reported. The objectives of this study were (1) to investigate the accuracy of dipyridamole stress first-pass myocardial perfusion MRI for diagnosing CAD (> 50% stenosis) and (2) to clarify whether additional delayed enhancement MRI has any clinical significance. We performed first-pass myocardial perfusion MRI in 102 consecutive patients (66 +/- 9 years old) suspected to have CAD or new lesions in patients with well-documented prior myocardial infarction (MI). Using a 1.5 T cardiac MR imager (GE CV/i), eight short axis MR images of the left ventricle were acquired by injecting gadolinium (0.1 mmol/kg) under dipyridamole infusion stress (0.56 mg/kg). Fifteen minutes later, aminophylline (250 mg) was injected and first-pass perfusion MRI was repeated in the resting state in order to evaluate both the presence of perfusion defect and delayed enhancement. The presence of perfusion defect and delayed enhancement was determined based on a visual qualitative analysis by the agreement of two separate readers who were blinded to any clinical information. Based on the stress and rest findings, no defect, reversible defect, or fixed defect with or without delayed enhancement was recorded in any patient. The MR findings revealed 76 CAD patients, including 24 MI patients with new lesions and 26 patients without CAD on coronary angiography. The presence of stress perfusion defect had a 93% sensitivity and an 85% specificity for diagnosing CAD. A fixed defect showed an 86% sensitivity and a 66% specificity for diagnosing a prior MI. Patients with a fixed defect with delayed enhancement had more significant stenosis in the infarct related artery than in those without any enhancement (11/26 vs 15/20, P < 0.05). Dipyridamole stress first-pass myocardial perfusion MRI using the FastCard EchoTrain was found to be a clinically useful and accurate modality for diagnosing CAD.     

Role for interleukin-6 and insulin-like growth factor-I via PI3-K/Akt pathway in the proliferation of CD56- and CD56+ multiple myeloma cells

OBJECTIVES: Several studies including ours have suggested that lack of CD56 in multiple myeloma (MM) defines a unique patient subset with poorer prognosis. However, the mechanism underlying this aggressive behavior of CD56(-) MM has not been well elucidated. Interleukin-6 (IL-6) or insulin-like growth factor I (IGF-I) induce proliferation of MM cells. In this study, we report about the relationship between CD56 expression and responsiveness to these cytokines. METHODS: We sorted out both CD56(-) and CD56(+) fractions from MM cell lines such as KMS-21-BM and U-266, and investigated their different responsiveness to IL-6 or IGF-I. Furthermore, we compared the effects of these cytokines on the regulation of cell-cycle distribution between CD56(-) and CD56(+) cells. RESULTS: Although CD56(-) cells in both KMS-21-BM and U-266 cells responded significantly to IL-6, CD56(+) cells did not. Ki-67(+) cells in the CD56(-) cells were significantly increased by IL-6. Western blotting showed that IL-6 phosphorylated Akt, and upregulated and downregulated the level of cyclin D1 and p27 protein in the CD56(-) KMS-21-BM cells, respectively. LY-294002 completely blocked these effects of IL-6. On the other hand, Ki-67(+) cells in the CD56(+) cells did not respond to IL-6. Anti-IGF-I mAb significantly reduced Ki-67(+) cells only in the CD56(+) cells. IGF-I phosphorylated Akt and upregulated cyclin D1 in the CD56(+) KMS-21-BM cells, which was completely blocked by LY294002. CONCLUSIONS: These results suggest that CD56(-) and CD56(+) MM cells could be stimulated by IL-6 and IGF-I, respectively, via PI3-K/Akt pathway, and provide useful information for anticytokine therapies.     

Mitral valve repair in a patient with acromegaly: case report.

A 61-year-old woman had acromegaly associated with mitral regurgitation (MR) resulting from prolapse of the posterior mitral leaflet. At the age of 51 years, the patient was diagnosed with hypertension and a cardiac murmur. She had the characteristic acromegalic appearance, but without visual disturbance. Blood chemistry revealed an elevated plasma concentration of growth hormone and glucose intolerance. Echocardiography showed remarkable dilation of the left ventricle and prolapse of the anterolateral commissure with severe MR. Magnetic resonance imaging of the brain revealed a pituitary microadenoma. MR was successfully corrected by quadrangular resection of the posterior leaflet, including the prolapsed portion, and prosthetic ring annuloplasty. The patient recovered uneventfully.