Hepatocellular carcinoma: Efficacy of transcatheter oily chemoembolization in relation to macroscopic and microscopic patterns of tumor growth among 100 patients with partial hepatectomy

Purpose: To evaluate the efficacy of transcatheter oily chemoembolization (TOCE) for hepatoceliular carcinoma (HCC) on the basis of microscopic and macroscopic findings postembolization. Methods: HCCs ranging in size from 0.5 to 13 cm (mean 3.6 cm) were obtained from partial hepatectomies of 100 consecutive patients who had undergone TOCE between 20 and 246 days (mean 59.5 days) prior to surgery. The efficacy of TOCE was assessed on the basis of the necrotic to live cell ratio of the tumors. The microscopic pattern of tumor growth was grouped into expanding type (complete capsule formation) and replacing type (incomplete or no capsule). There were five types of macroscopic groupings: single nodule, single nodule with extranodular growth (SNE), contiguous and noncontiguous multinodular, and massive growth type. Results: Among 79 cases with the expanding type, 29 (37%) had 100% HCC necrosis, but none with 100% necrosis were in the replacing type. By macroscopic grouping, the efficacy of TOCE decreased from the single nodule type (50% of patients had 100% necrosis) to the SNE type (21%), and the other types (9%).     

Effect of halothane and enflurane on hepatic blood flow and oxygen consumption in dogs

We investigated the relative effects of 0.5, 1.0, 1.5, 2.0 MAC halothane and enflurane, and concurrent noxious stimulus on hepatic blood flow and oxygen consumption in 14 mongrel dogs randomly divided into groups of seven each. Hepatic arterial and portal venous blood flow (HABF and PVBF, respectively) were measured continuously using ultrasonic transit time flow meter. Mean arterial blood pressure (MAP), cardiac index (CI), hepatic oxygen supply, and hepatic oxygen consumption (H _{O 2}) were measured. Halothane significantly deceased HABF, but not PVBF in a dose dependent manner. Enflurane did not affect HABF and PVBF significantly. MAP and CI decreased in both groups, with halothane producing more marked decreases than enflurane. H _{O 2} did not change with enflurane, but did with halothane, producing significant differences, with halothane being greater at 1.5, 2.0 MAC. A noxious stimulus only caused minor change in blood flow. The results suggest that liver blood flow and oxygen consumption are affected differently by halothane and enflurane and that halothane has a stronger tendency to cause an imbalance between liver oxygen supply and consumption than dose enflurane.(Masaki E, Yasuda N, Tanifuji Y et al.: Effect of halothane and enflurane on hepatic blood flow and oxygen consumption in dogs. J Anesth 3: 118–122, 1989)     

Effects of nitrendipine on the autoregulation of regional cerebral blood flow in the pithed rabbit

Summary Effects of the calcium-channel antagonist, nitrendipine, on the autoregulation of regional cerebral blood flow were studied by analysing the pressure-flow relationship in the cortex, subcortex and thalamus in pithed anesthetized rabbits. Arterial pressure was altered from 50 to 125 mm Hg by electrical stimulation of the spinal nerve roots. Regional blood flow was measured with the hydrogen clearance technique. Under control conditions, regional blood flow in the cortex, subcortex and thalamus did not change significantly within the range of mean arterial pressures of 50 to 100 mm Hg. Vascular resistance in each region rose significantly (P < 0.05) in a pressure-dependent manner. During the intravenous infusion of nitrendipine (0.3 and 1 g · kg^–1 · min^–1), blood flow to the three regions of the brain increased in a pressure-dependent manner when mean arterial pressure was increased from 50 to 125 mm Hg. The autoregulatory increase in regional vascular resistance was abolished. In addition, nitrendipine produced a blood pressure-dependent decrease of the vascular resistance in the subcortex and thalamus but not in the cortex. These results indicate that nitrendipine increases regional cerebral blood flows and suppresses regional autoregulations simultaneously. The autoregulatory adjustment in the cortex is more resistant to nitrendipine than that in the subcortex and thalamus. The observation that the action of nitrendipine was not the same in the three brain regions may be due to the vascular beds of these regions differing in their calciumchannel equipment.     

Association of the insertion/deletion polymorphism of the angiotensin I-converting enzyme gene in patients of migraine with aura

Recently, several angiotensin I-converting enzyme (ACE) inhibitors and an angiotensin II receptor blocker were demonstrated to have a clinically important prophylactic effect in migraine. ACE is one of the key enzymes in the rennin-angiotensin-aldosterone system, which modulates vascular tension and blood pressure. In humans, serum ACE levels are strongly genetically determined. Individuals who were homozygous for the deletion (D) allele showed increased ACE activity levels. To investigate the role of ACE polymorphism in headache, we analyzed the ACE insertion (I)/deletion (D) genotypes of 54 patients suffering from migraine with aura (MwA), 122 from migraine without aura, 78 from tension-type headache (TH), and 248 non-headache healthy controls. The ACE D allele were significantly more frequent in the MwA than controls (p<0.01). The incidence of the D/D genotype in MwA (25.9%) was significantly higher than that in controls (12.5%; p<0.01; odds ratio=5.26, 95% confidence interval: 1.69-16.34, adjusted for age and gender). No differences in the remaining groups were found. Our results support the conclusion that the D allele and the D/D genotype in the ACE gene is a genetic risk factor for Japanese MwA. There seems to be a possible relationship between ACE activity and the pathogenesis of migraine.     

Pathological analyses of long-term intracoronary Palmaz-Schatz stenting; Is its efficacy permanent?

BACKGROUND: Angiographic regression of luminal narrowing occurs 6 months to 3 years poststenting. However, after 4 years lesions progressed gradually and late restenosis was observed in 28% of 179 Palmaz-Schatz-stented lesions during the past 10 years. Elucidating its pathogenesis is pivotal to developing preventive strategies. METHODS AND RESULTS: Histopathological and immunohistochemical studies were performed in 19 stented coronary arteries obtained from 19 patients autopsied after noncardiac death 2-7 years poststenting. The quality/severity of chronic inflammatory cells (T lymphocytes, macrophages and multinucleated giant cells) infiltration around the stent struts that is observed even in the absence of restenosis depended on the time elapsed from stenting: a) 2 years postprocedure, in spite of angiographic regression during the first year and pathologically expressed as maturation of the neointimal scar, there was chronic inflammatory response evidence: neovascularization and lymphocyte infiltration, b) > or = 3 years: the neointimal smooth muscle cells were sparse with abundant proliferation of collagen fibers. Presence of slight helper/inducer T lymphocytes and mild macrophage infiltration around the stent struts was evident immunohistochemically, c) > or = 4 years: prominent infiltration by lipid-laden macrophages with strong collagen-degrading matrix metalloproteinase immunoreactivity was observed around the struts. In two of these arteries, the surface contacting the stent was focally disrupted and covered by nonocclusive mural thrombi. CONCLUSIONS: Stainless steel stents evoke a remarkable foreign-body inflammatory reaction to the metal. These persistent peri-strut chronic inflammatory cells may accelerate new indolent atherosclerotic changes and consequent plaque vulnerability.     

Usefulness of body surface mapping to differentiate patients with Brugada syndrome from patients with asymptomatic Brugada syndrome

We attempted to determine the usefulness of body surface mapping (BSM) for differentiating patients with Brugada syndrome (BS) from patients with asymptomatic Brugada syndrome (ABS). Electrocardiograms (ECG) and BSM were recorded in 7 patients with BS and 35 patients with ABS. Following the administration of Ic antiarrhythmic drugs, BSM was recorded in 5 patients with BS and 16 patients with ABS. The maximum amplitudes at J0, J20, J40 and J60 were compared between the 2 groups, as were 3-dimensional maps. The maximum amplitudes at J0, J20 and J60 under control conditions were larger in patients with BS than in patients with ABS (P < 0.05). A three-dimensional map of the ST segments under control conditions in patients with BS showed a higher peak of ST elevation in the median precordium compared to that for patients with ABS. Increases in ST elevation at J20, J40 and J60 following drug administration were greater in patients with BS than in patients with ABS (P < 0.05). Evaluation of the change in amplitude of the ST segment at E5 caused by Ic drug administration was also useful for differentiating between the 2 groups. In conclusion, BSM was useful for differentiating patients with BS from those with ABS.     

Dominant-Negative Rho, Rac, and Cdc42 Facilitate the Invasion Process of Vibrio parahaemolyticus into Caco-2 Cells

To clarify the invasive process of Vibrio parahaemolyticus, an invasion assay was performed using cells expressing dominant negative small GTPases of the Rho family. This assay showed that the dominant negative host phenotype facilitates bacterial invasion, suggesting that the mechanism of V. parahaemolyticus invasion differs from that reported for other invasive bacteria.     

Role of p27Kip1 and Cyclin-Dependent Kinase 2 in the Proliferation of Non-Small Cell Lung Cancer

The cell cycle is governed by a family of cyclin-dependent kinases (Cdks). Cdk2 forms a functional complex with cyclin E and plays a pivotal role in the regulation of G1/S transition. Cdk2 activity is negatively regulated by interactions with inhibitors. p27^Kip1, one of the most potent inhibitors of Cdk2, was recently identified as a powerful negative prognostic marker in non-small cell lung cancer as well as in colorectal and breast cancer. In the present study, the expression of p27 and Ki-67 antigen in nonneoplastic and cancerous lung tissues was determined by immunohistochemistry. After establishing that the antibody-measured p27 labeling index was a good reflection of the level of p27 expression measured by Western blotting, we show that p27 labeling index is decreased in cancerous lung tissues, compared with nonneoplastic lung tissues, and exhibits a significant inverse relation to the proliferation marker Ki-67 antigen, detected with monoclonal antibody MIB-1. Consistent with these data, all cancerous lung tissues showed enhanced degradation activity of p27 compared with nonneoplastic lung tissues and, in addition, increased levels of the phosphorylated form of Cdk2, as determined with Western blot analysis. The H1 histone kinase activity associated with Cdk2 was also increased in non-small cell lung cancers. Statistical analysis showed that proliferative activity as measured by MIB-1 labeling index was highly correlated with Cdk2 activity (r = 0.767, P < 0.0015). These results suggest that p27 and Cdk2 may play an important role in the proliferation of non-small cell cancer.