Spontaneous total necrosis of hepatocellular carcinoma: report of a case

We report on a 50-year-old man with a liver mass that, when surgically resected, was found to be a hepatocellular carcinoma that had undergone spontaneous complete necrosis without previous treatment. Histologically, no viable tumor cells were observed. The postoperative course was uneventful, and the patient is alive without evidence of recurrence about 5 years after surgery. Spontaneous total necrosis of hepatocellular carcinoma without previous treatment is rare. In particular, spontaneous total necrosis of a hepatocellular carcinoma that has been proven by histologic examination of a surgically resected liver specimen is extremely rare; only three cases of spontaneous complete necrosis of hepatocellular carcinoma have been reported previously. In this report, we present our unusual case and discuss possible causes of spontaneous total necrosis or regression of hepatocellular carcinoma.     

Conduction performance of collateral vessels induced by vascular endothelial growth factor or basic fibroblast growth factor

OBJECTIVE: In the present study, we delivered vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) gene to a rabbit model of hind limb ischemia utilizing an ex vivo method of gene transfer, and evaluated the functional performance of the developed collateral vessels. METHOD: The left femoral artery of a male Japanese White rabbit was excised to induce limb ischemia, and a section of skin was resected for culture of auto-fibroblasts. Twenty days later, the VEGF gene, bFGF gene or beta-galactosidase gene (LacZ) was adenovirally transferred to the cultured auto-fibroblasts (5x10(6) cells), and the next day, a pair of specifically infected fibroblasts (total 1x10(7) cells) was injected via the left internal iliac artery of the same rabbit. Pairs of transferred genes into the fibroblasts were as follows: LacZ/LacZ (control group), VEGF/LacZ (VEGF group), bFGF/LacZ (FGF group) and VEGF/bFGF (combination group). Twenty-eight days after cell administration, collateral development and its function were evaluated. RESULTS: Calf blood pressure ratio, resting blood flow of the left iliac artery and capillary density of ischemic muscle showed similar degrees of angiogenic effects in the VEGF and FGF groups, which were significantly greater than those in the control group. On the contrary, angiographic score, collateral conductance and smooth muscle cell (SMC)-positive vessel density in the FGF group were significantly greater than those in the VEGF group. In the combination group, collateral conductance showed synergistic effects, and in vivo blood flow and smooth muscle cell-positive vessel density revealed additive effects of VEGF and bFGF. CONCLUSION: These findings suggested that bFGF-induced collateral development exceeded VEGF-induced collateral development in the induction of arteriogenesis, and that combined gene delivery of VEGF and bFGF produced additive or synergistic effects of collateral development as compared with the effects induced by transfer of each gene alone.     

Angiotensin II plays an important role in maintaining blood pressure in postmenopausal women receiving hormone replacement therapy

BACKGROUND: We investigated the role of angiotensin (Ang) II in maintaining blood pressure (BP) by administering a small dose of candesartan, an Ang II type 1 receptor antagonist, in postmenopausal women receiving long-term hormone replacement therapy (HRT). METHODS: A single dose of 2 mg of candesartan was administered orally to 13 normotensive postmenopausal women receiving HRT (continuous combined conjugated estrogen and medroxyprogesterone acetate orally; HRT group) and 13 normotensive postmenopausal women not receiving HRT (control group). Both BP and heart rate (HR) were measured at baseline and at 1, 2, 3, 4, 5, and 6 h after administration. Plasma renin activity (PRA) and Ang I, Ang II, and bradykinin concentrations were measured at baseline and 4 h after the administration of candesartan. RESULTS: Candesartan lowered the BP and raised the HR in both groups. However, the decrease in BP was significantly greater in the HRT group than in the control group (P < .05), whereas no significant difference in the change in HR was observed between the two groups. In the HRT group, significant increases were found in PRA, Ang I, and Ang II (all P < .05) and a significant decrease in bradykinin (P < .01) with candesartan treatment. In the control group, candesartan as associated with an increase in PRA (P < .05) but not in Ang I, Ang II, or bradykinin. CONCLUSIONS: Based on our study results, Ang II plays an important role in maintaining BP in normotensive postmenopausal women receiving HRT. Maintenance of BP may be dependent on the balance between the hypertensive effect of Ang II and the hypotensive effect of bradykinin.     

Glycated high-density lipoprotein regulates reactive oxygen species and reactive nitrogen species in endothelial cells

Nonenzymatic glycosylation of plasma proteins may contribute to the excess risk of developing atherosclerosis in patients with diabetes mellitus. Although it is believed that high-density lipoprotein (HDL) is glycosylated at an increased level in diabetic individuals, little is known about a possible linkage between glycated HDL and endothelial dysfunction in diabetes. To clarify whether glucose-modified HDL affects the function of endothelial cells, we first examined herein the level of H(2)O(2) generation from cultured human aortic endothelial cells (HAECs) exposed to a glycated oxidized HDL (gly-ox-HDL) prepared in vitro. Incubation for 48 hours with 100 microg/mL of gly-ox-HDL induced significant release of H(2)O(2) from cells and gly-ox-HDL-induced H(2)O(2) formation was inhibited in the presence of diphenyleneiodonium, an inhibitor of NADPH oxidase. In addition, stimulation of HAECs with gly-ox-HDL for 48 hours elicited a marked downregulation of catalase and Cu(2+), Zn(2+)-superoxide dismutase (CuZn-SOD), suggesting H(2)O(2) formation by gly-ox-HDL to be due to a disturbance involving oxidant and antioxidant enzymes in the cells. Treatment of HAECs with gly-ox-HDL attenuated the expression of endothelial nitric oxide synthase (eNOS), but not inducible nitric oxide synthase (iNOS), and this was followed by decreased production of nitric oxide (NO) by the cells. Furthermore, in vitro experiments with glycated HDL (gly-HDL) in the presence of 2 mmol/L EDTA and Cu(2+)-oxidized HDL suggested the effect of gly-HDL on endothelial function to be possibly potentiated by additional oxidative modification. Taking all of the above findings together, gly-ox-HDL may lead to the deterioration of vascular function through altered production of reactive oxygen species and reactive nitrogen species in endothelial cells.     

A large outbreak of Legionnaires' disease due to an inadequate circulating and filtration system for bath water--epidemiologic manifestations

OBJECTIVE: To study the epidemiologic manifestations of a large outbreak of Legionnaires' disease due to an inadequate circulating and filtration system for bath water. PATIENTS: In June 2000 at Ishioka City, Ibaraki Prefecture, a large outbreak of Legionnaire's disease occurred, as a result of an inadequate circulating and filtration system for communal bath water. This outbreak was the worst ever experienced in Japan, involving a total of 34 patients (20 confirmed, 14 probable), 3 of whom died. MEASUREMENTS AND RESULTS: Legionella pneumophila serogroup 1 was isolated from sputum culture in two patients. Bacteriological culture of the public bath water subsequently yielded large numbers of Legionella species. Cleavage of genomic DNA showed that restriction fragment patterns coming from clinical and environmental isolates of L. pneumophila serogroup 1 were closely related, focusing the inquiry to a public bathhouse where a circulating filtration system was suspected as the source of infection. CONCLUSIONS: It was later concluded that the circulating filtration system adopted for bath water was marred by a serious design flaw that subsequently caused the mass outbreak. Specifically, a line of the bath water was being returned to the bath without undergoing heat exchange or sterilization by chlorine; and the Legionella species that had proliferated in the filter and the bright stone filtration unit were allowed to return to the bath, eventually culminating in a mass infection.     

Long-term follow up of esophageal varices after balloon-occluded retrograde transvenous obliteration for gastric varices.

Aim: Because the procedure of balloon-occluded retrograde transvenous obliteration (B-RTO) causes extensive thrombosis of the major shunt that connects the spleen and gastric/renal venous systems, an increase in portal pressure is unavoidable. The aim of the present study was to assess the long-term outcome of B-RTO, including changes in esophageal varices. Methods: B-RTO was conducted in 22 patients with gastric varices, who were divided according to the severity of esophageal varices at baseline; there were no esophageal varices (n = 7), F(1) varices (n = 11), and F(2) varices (n = 4). The outcome measures included the development/worsening of esophageal varices after B-RTO and survival rates. Results: The cumulative bleeding-free probability for all 22 patients at 3 years after B-RTO was 100%. The overall 3-year survival was 94.4%. Seven patients who had no esophageal varices prior to B-RTO did not develop any after the procedure. Seven (63.6%) of the 11 patients with stage F(1) esophageal varices prior to B-RTO showed no changes in the varices after B-RTO, while two patients progressed to F(2) varices and two developed F(3) varices. The cumulative treatment-free probability of the esophageal varices at 24 months after B-RTO was 100% for patients without esophageal varices at baseline, 80.8% for patients with pre-existing F(1) varices, and 75% for those with pre-existing F(2) varices. Conclusion: Although the B-RTO procedure is considered useful for the treatment of gastric varices, changes in hemodynamics due to obliteration of this major shunt must be taken into account and observed closely.     

Long-term effects of captopril on passive sodium permeability and contractility in vascular smooth muscles of spontaneously hypertensive rats

Long-term effects of captopril on passive sodium permeability and cellular sodium concentration in the aorta of spontaneously hypertensive rats were examined in terms of contractile properties of the muscle. In cold lithium solution, cellular sodium in the aorta isolated from spontaneously hypertensive rats leaked more rapidly than did that isolated from Wistar Kyoto rats (WKY), suggesting an increased sodium permeability in the aorta of spontaneously hypertensive rats. Six weeks of treatment with captopril reduced the increased sodium permeability after hydralazine had failed. Inhibition of the sodium pump by incubating the aorta in potassium-free solution produced a slowly developing contraction which was associated with accumulation of cellular sodium. Both the magnitude of contraction and the accumulation of sodium during exposure to potassium-free solution for 1 hour were significantly less in the aorta isolated from spontaneously hypertensive rats treated with captopril compared with those from control spontaneously hypertensive rats. These data suggest that after prolonged administration, captopril alters the abnormal sodium permeability of vascular smooth muscle in spontaneously hypertensive rats and that the restoration of normal permeability reduces vascular tone.     

Extended-spectrum beta-lactamase (ESBL) produced by Escherichia coli and Klebsiella pneumoniae isolated from Teikyou University Hospital--the first report

We studied the cefotaxime (CTX)-resistant (MIC > or = 32 micrograms/ml) clinical isolates of E. coli and K. pneumoniae in Teikyo University Hospital from 1990 to 1996. The incidence of CTX-resistant isolates was 0.4% (6/1,282) in E. coli and 0.6% (7/1,044) in K. pneumoniae, in 1990. In 1995, the incidence of CTX-resistance increased to 1.7% (50/2,910) in E. coli (p = 0.0013) and 7.2% (144/1,996) in K. pneumoniae (p < 0.0001). These species have been detected in the stool (86 isolates), urine (59 isolates), sputum (15 isolates), pus (15 isolates), throat (10 isolates) and others (12 isolates) in 1995. MIC50 of ampicillin (ABPC), ABPC with clavlanic acid (CVA) 5 micrograms/ml, piperacillin (PIPC), PIPC with CVA 5 micrograms/ml, ceftazidime, CTX, ceftizoxime, cefpodoxime, cefepime, aztreonam, cefmetazole, latamoxef, and imipenem used against 33 isolates (11 isolates of E. coli, 22 isolates of K. pneumoniae), which were detected in 1996-1997, was > 512 micrograms/ml, 8 micrograms/ml, > 512 micrograms/ml, 8 micrograms/ml, 4 micrograms/ml, > 512 micrograms/ml, 16 micrograms/ml, > 512 micrograms/ml, 256 micrograms/ml, 32 micrograms/ml, 2 micrograms/ml, 0.25 microgram/ml and 0.25 microgram/ml, respectively. This susceptibility pattern were very similar to the Toho-1 type beta-lactamases producing strains.