Prognostic factors in the treatment of hepatocellular carcinoma with transcatheter arterial embolization and arterial infusion.

From January 1986 to December 1988, a prospective trial of transcatheter arterial treatment was carried out for hepatocellular carcinoma (HCC). Two hundred seventy-five patients were included. Okuda's staging system was employed. Patients with Stage I and II HCC were treated by transcatheter arterial embolization (TAE) with a gelatin sponge containing an anti-cancer agent (protocol 1a); a gelatin sponge and iodized oil mixed with an anti-cancer agent (protocol 1b); or iodized oil mixed with an anti-cancer agent (protocol 2). Patients with Stage III HCC were treated with iodized oil with anti-cancer agent (protocol 2). As an exception, patients with an unsuccessful superselective catheterization into the proper hepatic artery by Seldinger technique or obstruction of the main trunk of the portal vein were treated with percutaneous transcatheter arterial infusion into the common hepatic artery regardless of stage (protocol 3). Tumor type and extension, area of tumor involvement, portal vein involvement, method of treatment, and presence of ascites and icterus were found to be the significant factors for an initial response to therapy. Treatment method was the most important factor. Respective survival rates at 1 and 2 years were 70.9% and 55.3% for protocol 1a; 62.3% and 43.8% for protocol 1b; 37.8% and 18.3% for protocol 2; and 16.5% and 0% for protocol 3. Many factors proved to significantly influenced prognosis; however, tumor type had the most important prognostic significance followed by AFP value, ascites, treatment protocol, and area of tumor involvement.     

Embolic myocardial infarction and left ventricular rupture due to mitral valve endocarditis.

A left ventricular rupture due to embolic myocardial infarction is extremely rare. A 72-year-old woman developed an acute embolic myocardial infarction and mitral regurgitation due to infective endocarditis. Two days after the infarction, a left ventricular free wall rupture occurred after transesophageal echo examination. She received an epicardial patch and mitral valve replacement. Perioperatively, an intra-aortic balloon pump and long-term antibiotics were used. The postoperative course was uneventful, and she is doing well 10 months after surgery.     

Big mitogen-activated protein kinase 1 (BMK1)/extracellular signal regulated kinase 5 (ERK5) is involved in platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell migration

Big mitogen-activated protein kinase 1 (BMK1), also known as extracellular signal-regulated kinase 5 (ERK5), is a newly identified member of the mitogen-activated protein (MAP) kinase family. Recently, several studies have suggested that BMK1 plays an important role in the pathogenesis of cardiovascular disease. To clarify the pathophysiological significance of BMK1 in the process of vascular remodeling, we explored the molecular mechanisms of BMK1 activation in vascular smooth muscle cells (VSMCs). From the results of co-immunoprecipitation and immunoblotting analyses, it was found that platelet-derived growth factor (PDGF), a known potent mitogen, activated BMK1 and triggered the Gab1-SHP-2 interaction in rat aortic smooth muscle cells (RASMCs). The abrogation of SHP-2 phosphatase activity by transfection of the SHP-2-C/S mutant suppressed PDGF-stimulated BMK1 activation. Infection with an adenoviral vector expressing dominant-negative MEK5alpha, which can suppress PDGF-stimulated BMK1 activation to the control level, inhibited PDGF-induced RASMC migration. Moreover, we observed an increase of BMK1 activation in injured mouse femoral arteries. From these findings, it is suggested that BMK1 activation leads to VSMC migration induced by PDGF via Gab1-SHP-2 interaction, and that BMK1-mediated VSMC migration may play a role in the pathogenesis of vascular remodeling.     

Familial apoceruloplasmin deficiency associated with blepharospasm and retinal degeneration

A 52-year-old woman had a newly recognized disorder of familial hypoceruloplasminemia, blepharospasm, retinal degeneration, and high-density areas in CT of the basal ganglia and liver scan. Immunofixation electrophoresis disclosed apoceruloplasmin deficiency. Kinetic, x-ray analysis, and histochemical study showed accumulation of iron in liver and brain, but not of copper. Intestinal copper absorption was reduced, but liver uptake was increased. Ceruloplasmin is involved in iron metabolism, and the findings suggest that hypoceruloplasminemia due to lack of apoceruloplasmin was causally linked to the iron deposition in basal ganglia and other organs, leading to blepharospasm and retinal degeneration.     

Traumatic degeneration of transected myelinated fibers of the mouse sciatic nerve.

Traumatic degeneration of myelinated fibers was studied by electron microscopy over 5 days following transection of mouse sciatic nerve. Special attention was paid to the mechanism which separates the degenerating part, while preserving the viable part of the axon. Immediately after transection, the opened end of the proximal stump revealed extensive subcellular changes including the disorganization of neurofilaments, and disruption of mitochondria and axonal endoplasmic reticulum (SER). Subsequently, vesicles of round and tubular profiles filled up the whole area of the stump end, and proximal to it appeared a neurofilament-predominant area characterized by randomly oriented neurofilaments and normally appearing mitochondria and SER. Characteristic membranous demarcations occurred in early periods at the border between the vesicle accumulation and the neurofilament-predominant areas, and later also within these areas. The demarcation membranes formed both by invagination of the surface plasma membrane and, probably, by fusion of the large vesicles. These became prominent with time, dividing the axoplasm into compartments of varying sizes, which gradually underwent degeneration and were liberated from the parent axon. Occurrence of autophagic vacuoles was characteristic of the degenerating portions of the parent axon. Thus, by the function of demarcation membranes, the parent axon to be preserved could remain membrane-bound, while the degenerating parts were shed off.     

Veno-arterial ECLA (extracorporeal lung assist) for severe respiratory failure due to meconium aspiration

A full term newborn female, 3262g, aspirated meconium at birth and began to suffer from severe hypoxia and acidosis due to progressing pneumonitis, pneumothorax and pneumomediastinum. She also had severe hypotension and anuria. Venoarterial ECLA with a Kolobow membrane lung via the right internal jugular vein and the right common carotid artery was initiated. Blood gas parameters and blood pressure improved, and urine output increased to normal. ECLA permitted a reduction in FIO2 and airway pressure of mechanical ventilation, as well as frequent lavage of the lung. As the physical condition improved, the bypass flow was gradually decreased from 200 ml.kg-1.min-1 at the start to 130 ml.kg-1.min-1 for maintenance, then to 25 ml.kg-1.min-1 at the end. Bleeding throughout the ECLA for 69 hours could be minimized by a meticulous control of the activated coagulation time with a minimum dose of heparin and the transfusion of fresh frozen and platelet rich plasma. After ECLA, the carotid artery was simply ligated, and mechanical ventilatory support was carried out for 5 days. Her condition improved and she left the hospital without any neurological sequelae. ECLA will become an effective means of life support for a baby with severe MAS irresponsive to conventional ventilatory support.     

A case of metastatic optic nerve head and retinal carcinoma with vitreous seeds

Metastasis directly to the optic nerve head without choroidal involvement is rare. We report a case of metastatic adenocarcinoma of the optic nerve head and retina with vitreous seeds which was observed in a 45-year-old Japanese male. The primary site of the lesion was clinically the upper lobe of the left lung. Tumor emboli were observed in the central retinal vein. Vitreous seeds appeared to have arisen from a necrotic area and papillary projections of the tumor.     

Serotonin and tryptamine metabolism in the acute hepatic failure model: changes in tryptophan and its metabolites in the liver, brain and kidney

When heat-killed Propionibacterium acnes, a gram-positive anaerobe, is intravenously injected into mice followed by an intravenous injection of gram-negative lipopolysaccharide (LPS) 7 days later, most of the mice die of massive hepatic cell necrosis within 24 hours of LPS injection. Using this experimental model, acute hepatic failure was induced in mice, and the tryptophan metabolism in the liver, brain and kidney was studied. As a result, the tryptophan level was remarkably high in all three organs, and the metabolism of both the tryptamine pathway and serotonin pathway was induced. However, in the brain, the tryptamine metabolism was more induced compared to the serotonin, suggesting that the metabolites of tryptamine, may be involved in hepatic encephalopathy.