Myocardial protective effect of lidocaine during experimental off-pump coronary artery bypass grafting.

Off-pump coronary artery bypass grafting (OPCABG) has recently gained popularity. During OPCABG, patients remain vulnerable to ischemic-reperfusion injury due to a temporary coronary occlusion without any active cardioprotection. Some strategies such as ischemic preconditioning (IP) and an intracoronary shunt have been applied with a view to minimizing the effects of ischemia, but the effects of these strategies remain controversial. This study was carried out to investigate the protective effect of lidocaine against myocardial ischemic-reperfusion injury. Twenty-one pigs were assigned to three groups, each consisting of seven pigs. In the control group, using a left internal thoracic artery (LITA) bypass circuit, the left anterior descending coronary artery (LAD) was occluded for 45 min followed by two hours of reperfusion. In the IP group, five min of occlusion followed by 15 min of reperfusion was performed. In the lidocaine group, 2 mg/kg of lidocaine was administered directly into the LAD just before the LAD occlusion. Infarct size expressed as a percentage of the area at risk was significantly smaller in the lidocaine group (2.7+/-4.2%) than in the control group (79.9+/-6.0%, p<0.001) or the IP group (57.0+/-25.9%, p<0.001). Lidocaine exhibited a potent myocardial protective effect in the present OPCABG model.     

Discovery of orally active nonpeptide bradykinin B2 receptor antagonists

Orally active nonpeptide bradykinin (BK) B2 receptor antagonists have been discovered by using directed random screening and chemical modification. These compounds displaced [3H]BK binding to B2 receptors in guinea-pig ileum membranes, rat uterus membranes and human lung fibroblasts with nanomolar IC50s. They did not inhibit different specific radio-ligand bindings to other receptor sites including B2 receptors. In isolated guinea-pig ileum preparations, these compounds had no agonistic effect on smooth muscle contraction at 10(-6) M, and caused parallel rightward shifts of the concentration-response curves to BK on contraction with higher p A2 values. They also blocked human B2 receptor-mediated phosphatidylinositol hydrolysis without agonistic effect. In vivo, the oral administrations of these antagonists potently inhibited BK-induced bronchoconstriction in guinea-pigs. They also reduced carrageenin-induced paw edema and caerulein-induced pancreatitis in rats. Moreover, these compounds alleviated kaolin-induced pain in mice by oral administration. These results show that our compounds are potent, selective, and orally active BK B2 receptor antagonists and that they may have therapeutic potential against inflammatory diseases and pain.     

Clinical application of intrathecal lidocaine administration in surgery of the descending thoracic aorta

We studied the protective effects of intrathecally administered lidocaine against ischemic spinal cord injury during surgery. Seven patients (mean age 63.7 years, malefemale=61) with descending thoracic aortic aneurysms underwent reconstructive surgery. Following intrathecal lidocaine administration (10 ml), the operation was performed under femorofemoral bypass with an oxygenator. The aorta was cross-clamped at the distal end of the descending thoracic aorta and the proximal end of the lesions. The cross-clamping time was 47.1±23.3 minutes (mean ± SD). The operative procedure was total replacement of the descending thoracic aorta in five cases and patch closure in two. There were no operative deaths but paraparesis developed in two cases of total replacement. Neurological deficit was transient and disappeared in one case. In the other case, with 88 minutes of normothermic aortic cross-clamping, paraparesis gradually improved but was persistent after 7 months of follow-up. Graft anastomosis at the distal aortic arch was time consuming in this case and presumably caused prolonged spinal cord ischemia. Intrathecal administration of lidocaine was likely to reduce ischemic spinal cord injury and increase tolerance of the spinal cord to ischemia caused by prolonged aortic cross-clamping. This method was considered to provide a useful assistance to expand the safety limit of spinal cord ischemia in surgical reconstruction of the descending thoracic aorta requiring aortic occlusion. Tissue protective effects of intrathecal lidocaine administration may be further augmented by combining with deep hypothermia.     

Hemiparkinsonism associated with the unilateral striatal necrosis: a case report

We report a patient with hemiparkinsonism associated with unilateral striatal necrosis of the contralateral side. The patient was an 18-year-old woman who had a two-month-history of difficulty in executing skilled movements with her right upper extremity. Neurological examination revealed that she had cogwheel rigidity and bradykinesia in her right upper and lower extremities. MRI revealed a well-delineated low signal intensity in T1-weighted and high signal intensity in T2-weighted images in the region of the putamen on the left side. Her laboratory data were unremarkable and mitochondrial gene mutation studies revealed no abnormality. It is extremely rare to encounter a case of parkinsonism associated with unilateral striatal necrosis.     

Clinicopathologic differences between early gastric remnant cancer and early primary gastric cancer in the upper third of the stomach

BACKGROUND/AIMS: This study was designed to clarify the clinicopathologic characteristics and survival in early gastric remnant cancer and compare with early primary cancer in the upper third of the stomach. METHODOLOGY: Twenty-five patients with early gastric remnant cancer, who underwent resection at Kanagawa Cancer Center and First Department of Surgery, Yokohama City University between 1974 and 1996 were evaluated in this study. Various clinicopathologic characteristics, such as age, sex, symptoms, size of tumor, depth of invasion, lymph node metastasis, cell differentiation, and survival were investigated and early gastric remnant cancer was compared with early primary cancer in the upper third of the stomach. RESULTS: According to the macroscopic type, protruded type such as I or II type accounted for a great majority in early gastric remnant cancer, while II c depressed type was common in early primary cancer in the upper third of the stomach, comprising 64.2% of all cases. Pathological examination disclosed that well-differentiated carcinoma and mucosal carcinoma were more frequently observed in early gastric remnant cancer than in early primary cancer in the upper-third of the stomach. The 5-year survival rate was 83.5% for early primary cancer in the upper-third of the stomach. In contrast, no patients experienced recurrence after operation for early gastric remnant cancer. CONCLUSIONS: From the view point of clinicopathological evaluation, gastric remnant cancer is a special from of gastric cancer. A follow-up program is important in order to detect early gastric remnant cancer. A low incidence of lymph node metastasis suggests that endoscopic mucosal resection of the tumor or limited operation could be performed under strict indication.     

Pharmacobezoar complicating treatment with sodium alginate

We encountered a gastric bezoar that had developed in a 9-year-old girl treated with sodium alginate (Alloid G) for acute gastritis associated with systemic lupus erythematosus. A hard mass palpated in the left upper abdomen proved, upon gastric endoscopy, to be an intragastric foreign body. Sodium alginate was detected in an analysis of a sample from this bezoar. In an in vitro simulation, sodium alginate solidified when mixed with the patients other medicines. The bezoar caused no complications, and disappeared spontaneously after discontinuation of the medications. This case indicates that this sodium alginate preparation, Alloid G, can be a cause of pharmacobezoar.     

Blood pressure after treatment with sodium–glucose cotransporter 2 inhibitors influences renal composite outcome: Analysis using propensity score-matched models

Aims/IntroductionSodium–glucose cotransporter 2 inhibitors (SGLT2i) improve renal outcome in patients with type 2 diabetes mellitus, but the mechanism is not fully understood. The aim of this retrospective study was to assess the association of achieved blood pressure with renal outcomes in Japanese type 2 diabetes mellitus patients with chronic kidney disease.Materials and MethodsWe assessed 624 Japanese type 2 diabetes mellitus patients with chronic kidney disease taking SGLT2i for >1 year. The patients were classified as those with post‐treatment mean arterial pressure (MAP) of ≥92 mmHg (n = 344) and those with MAP of <92 mmHg (n = 280) for propensity score matching (1:1 nearest neighbor match with 0.04 of caliper value and no replacement). The end‐point was a composite of progression of albuminuria or a decrease in the estimated glomerular filtration rate by ≥15% per year.ResultsBy propensity score matching, a matched cohort model was constructed, including 201 patients in each group. The incidence of renal composite outcome was significantly lower among patients with MAP of <92 mmHg than among patients with MAP of ≥92 mmHg (n = 11 [6%] vs n = 26 [13%], respectively, P = 0.001). The change in estimated glomerular filtration rate was similar in the two groups; however, the change in the albumin‐to‐creatinine ratio was significantly larger in patients with MAP of <92 mmHg.ConclusionsIn Japanese type 2 diabetes mellitus patients with chronic kidney disease, blood pressure after SGLT2i administration influences the renal composite outcome. Blood pressure management is important, even during treatment with SGLT2i.     

Purification and properties of porcine polymorphonuclear cells

A method for the rapid separation of highly purified populations of porcine polymorphonuclear cells from whole blood is described. Porcine blood, anti-coagulated with EDTA, was layered over a discontinuous Percoll gradient (62.5% and 75%) and then centrifuged at 400 X g for 25 min. This results in the formation of a band of cells at the interface of the two Percoll layers which is greater than 99% granulocytes (93.8 +/- 1.8% neutrophils and 5.3 +/- 1.8% eosinophils) with a 77% recovery. The mononuclear cells remain above the 62.5% Percoll layer, and most erythrocytes pellet to the bottom of the tube. The isolated porcine granulocytes were found to respond to opsonized zymosan, phorbol myristate acetate (20 ng/ml), and the calcium ionophore A23187 (10(-5) M) in chemiluminescence assays with kinetics similar to those of human granulocytes. The porcine cells did not respond to the chemotactic peptide N-formyl-methionyl-leucyl-phenalanine (FMLP; 10(-6) M) unlike the human granulocytes which display a very rapid response to FMLP. Both porcine and human granulocytes readily changed shape by elongating and developing pseudopods when exposed to zymosan-activated serum, but only human granulocytes changed on exposure to FMLP. Thus, porcine granulocytes may be rapidly isolated on discontinuous Percoll gradients with little mononuclear cell contamination. Porcine and human PMN have similar oxidative and chemotactic responses, but porcine PMN differ from human granulocytes in the inability of porcine granulocytes to respond to FMLP.