The effect of cyclosporine on hepatic ischemia was investigated. Hepatic ischemia was produced for 90 min in mongrel dogs. Experimental dogs were divided into three groups as follows: group A (control group), group B (CsA pretreatment group), group C (CsA posttreatment group). CsA was administered at a dose of 10 mg/kg body weight/day for 3 days in the pre- or postoperative period. Survival rates were 61.5% in group A, 84.6% in group B, and 30.8% in group C. Enzymatic activity such as aspartate aminotransferase and lactate dehydrogenase was highest in group C, lowest in group B, and intermediate in group A. Opposite results were obtained for serum albumin concentrations. The mechanisms of the effect was investigated using a 60-min hepatic ischemia model. Serum levels of beta-glucosidase and beta-galactosidase in group B were lower than those in group A and group C. Electronmicroscopic specimens taken at 16 h after 60-min hepatic ischemia demonstrated that the extent of ischemic injury was mildest in group B. The present study demonstrated a beneficial effect on hepatic ischemia of CsA administered for 3 days prior to the ischemia. One of the mechanisms for this beneficial effect could be the stabilization of lysosomal membranes. These results suggest that CsA should be administered to a donor before organ harvesting for liver transplantation because of this beneficial effect.
The effects of pretreatment with cyclosporine, allopurinol, or methylprednisolone on ischemia-reperfusion injury of the liver were investigated. A total of 32 adult mongrel dogs that received one of the pretreatments were divided into four groups and were subjected to 90 min liver ischemia. Serum activities of aspartate aminotransferase (s-AST) and lactate dehydrogenase, (s-LDH) as well as animal survivals were used as indicators of liver injury. The elevation of both s-AST and s-LDH was significantly suppressed by pretreatment with cyclosporine as much as by allopurinol. However a significant improvement in animal survival was obtained only in the cyclosporine-pretreated group. Pretreatment with methylprednisolone did not affect either the activities of s-AST and s-LDH or animal survivals when compared with the control group. These data suggest that cyclosporine is a potent protector against ischemic liver injury--as effective as allopurinol or methylprednisolone. Although the precise mechanism of the effect of cyclosporine on liver ischemia still remains unknown, these observations may be of use in liver transplantation.
Abstract During the past 8 years we have treated 268 patients with primary hepatocellular carcinoma (HCC); total extirpation of the tumor was carried out in 138. Thirty-one of the patients with resectable HCCs had already been treated with transcatheter arterial embolization (TAE) of the liver before they were referred to us. The clinical values of preoperative TAE were retrospectively evaluated for those 31 patients and for the remaining 107 patients without TAE. There were no substantial differences between the two study groups in the clinical and histopathologic backgrounds. No differences were observed in the extent of liver resection, estimated blood loss during surgery, and operation time. During surgery, however, troublesome intra-abdominal complications relevant to TAE were encountered in 15 patients, and detection of tumors was impossible, even with intraoperative ultrasonography, in five patients in the group with TAE. Such findings were not present in any of the patients without TAE. Postoperative morbidity and mortality rates were similar in the two groups. There was no significant difference in the rate of recurrence of tumor in the liver, but the recurrence time was significantly shorter in the group with TAE. TAE did not improve the long-term survival rates in patients either with or without cirrhosis. Results of our study seem to indicate that preoperative TAE is meaningless in the treatment of resectable HCCs and therefore should be avoided, particularly in patients with advanced cirrhosis of the liver.
Disruption of granulocyte/macrophage colony-stimulating factor (GM-CSF) signalling causes pulmonary alveolar proteinosis (PAP). Rarely, genetic defects in neonatal or infant-onset PAP have been identified in CSF2RA. However, no report has clearly identified any function-associated genetic defect in CSF2RB.
Methods and results
The patient was diagnosed with PAP at the age of 36 and developed respiratory failure. She was negative for GM-CSF autoantibody and had no underlying disease. Signalling and genetic defects in GM-CSF receptor were screened. GM-CSF-stimulated STAT5 phosphorylation was not observed and GM-CSF-Rβc expression was defective in the patient9s blood cells. Genetic screening revealed a homozygous, single-base deletion at nt 631 in exon 6 of CSF2RB on chromosome 22, which caused reductions in GM-CSF dependent signalling and function. Both parents, who were second cousins, showed no pulmonary symptoms, and had normal GM-CSF-signalling, but had a CSF2RB allele with the identical deletion, indicating that the mutant allele may give rise to PAP in an autosomal recessive manner.
Conclusions
This is the first report identifying a genetic defect in CSF2RB that causes deficiency of GM-CSF-Rβc expression and impaired signalling downstream. These results suggested that GM-CSF signalling was compensated by other signalling pathways, leading to adult-onset PAP.
Imaging diagnosis of Alzheimer disease (AD), the leading cause of dementia, requires evaluation of the extent of hippocampal atrophy. Coronal magnetic resonance (MR) images of patients with AD often demonstrate outward rotation of the hippocampus that is altered from a long horizontal elliptical to a long vertical elliptical shape. Such rotation may be related to the disease process of AD.To determine whether hippocampal rotation is associated with AD, we investigated MR images from 11 patients with AD and 11 normal controls, measuring the hippocampal angle (HA) and the volume of the left hippocampus on coronal T(1)-weighted MR images. The HA is the angle between a horizontal line orthogonal to the falx cerebri and the uncal sulcus line between the deepest point of the uncal sulcus and the point nearest to the side of the ambient cistern in the uncal gyrus facing the uncal sulcus. The HA is measured on the most rostral slice in which the uncal sulcus can be identified and increases with hippocampal rotation.We found correlation between the HA and standardized hippocampal volume in the AD group, but not in controls.Hippocampal rotation is a new marker associated with the pathology of AD.
Primary chronic osteomyelitis (PCO) of the jaw is a rare condition of unknown etiology with severe pain and/or facial swelling. In this article, a 63-year-old man whose severe pain caused by PCO of the mandible was treated with intravenous administration of lidocaine and magnesium is described. At the first visit, paresthesia on the right lower lip and chin was noted in an extraoral examination, and the results of an intraoral examination and laboratory examination were normal. Radiographic findings showed a ground glass-like opaque image and a bone resorption image on the right mandible. The patient was clinically diagnosed as having PCO. Pain control was difficult with conventional treatment, but successful pain control was achieved with intravenous administration of lidocaine and magnesium. The results suggested that intravenous administration of lidocaine and magnesium could be a new therapy for refractory PCO of the jaw.
Objectives: The aim of this study is to discuss the pathological course of chronic osteomyelitis of the mandible by investigating a correlation between CT and histopathological findings and to argue the usefulness of CT examination in the evaluation of mandibular chronic osteomyelitis. Methods: CT images obtained between 1997 and 2004 of 62 lesions in 60 patients with chronic osteomyelitis involving the mandible were reviewed retrospectively. CT images obtained at initial examination or pre-operative evaluation were reviewed and CT findings of affected bone were classified into three patterns: bone-defect pattern, frosted-glass pattern and compact-bone pattern. In 7 of 62 lesions, CT images and histopathological specimens were selected to obtain a side-by-side comparison in order to clarify what histopathological features reflect those three patterns of CT findings. Additionally, the correlations among the three patterns in the course of mandibular chronic osteomyelitis were also assessed. Results: The areas of bone-defect pattern, frosted-glass pattern and compact-bone pattern observed on CT images were revealed to indicate fibre-rich granulation tissue, new formation of bony trabeculae and thickening of bony trabeculae on histopathological findings, respectively. Conclusions: It was considered that these three patterns are significant in the evaluation of the process of the course of chronic osteomyelitis. We advocate that CT is useful to grasp the complex pathological conditions of chronic mandibular osteomyelitis.
