We evaluated the focal therapeutic effect of oily carcinostatic agents administered by transcatheter arterial infusion (TAI) as the initial therapy in patients with hepatocellular carcinoma in a randomized controlled clinical trial. Group A (19 patients) received 4 mg of styrene maleic acid neocarzinostatin in 4 ml of Lipiodol, and group B (18 patients) received 100 mg of epirubicin in 4 ml of Lipiodol via the tumor feeding arteries as peripherally as possible. The grade of Lipiodol accumulation and the tumor regression rate were determined 2 weeks after TAI by computerized tomography. Adverse effects within 2 weeks after TAI were evaluated by subjective signs and symptoms such as fever (maximum body temperature) and the frequency of shaking chills and abdominal pain, and by biochemical parameters such as albumin, prothrombin time, and aspartate and alanine aminotransferases. Lipiodol accumulation in the tumor was significantly greater in group A (12/19; 63.2% showing grade IV Lipiodol accumulation) than in group B (3/18; 16.7% showing grade IV) (P<0.05). The tumor regression rate was also significantly greater in group A (8/17; 47.1% showing more than 25% tumor regression) than in group B (1/13; 7.7% showing more than 25% tumor regression) (P<0.05). Although clinically significant elevations of aminotransferases and reductions of cholinesterase, and shaking chills were observed more often in group A than in group B (P<0.0001), these factors had little influence on the clinical outcome. Our results suggest that styrene maleic acid neocarzinostatin in Lipiodol exerts a more favorable focal therapeutic effect than does epirubicin in Lipiodol in the initial treatment of hepatocellular carcinoma.

Antineoplastic Agents↗

PubMed2000

Chronic pancreatitis in Japan: is alcoholic pancreatitis decreasing?

Explore the source record for details and available documents.

Chronic Disease↗

PubMed2000

Cronkhite-Canada syndrome: report of two cases.

Two cases of Cronkhite-Canada syndrome are reported. In the first case, a 56-year-old woman had an adenoma of the colon, arising within the Cronkhite-Canada polyps, which was removed by endoscopic polypectomy. This suggests possible neoplastic transformation of polyps in this syndrome. She achieved remission with corticosteroids, but the polyposis recurred (only in the stomach) 7 months after the remission. In the recurrent polyposis, corticosteroid therapy resulted again in complete remission, which has lasted for 5 years. In the second case, a 69-year-old man developed typical manifestations of the syndrome while under emotional stress. He had a past history of chronic pityriasis lichenoides, and serum antinuclear antibody was positive. These findings suggested a possible role of autoimmune response in the pathogenesis of the syndrome. Corticosteroids were also effective in this patient.

Adenoma↗

PubMed2000

Plasma nitrite/nitrate concentrations as a tumor marker for hepatocellular carcinoma.

Since plasma concentrations of nitrite/nitrate, the stable end-products of nitric oxide, increase in patients with hepatocellular carcinoma (HCC) correlatively to tumor volume, we examined the ability of plasma nitrite/nitrate to discriminate between those patients with HCC and those without and compared the diagnostic performance of the parameter with that of serum alpha-fetoprotein (AFP) concentrations. Plasma nitrite/nitrate and serum AFP concentrations were measured using a Griess reaction and a solid phase enzyme immunoassay, respectively. Eighty-nine patients with chronic liver diseases (CLD) with (n=39) or without HCC (n=50) and 50 healthy control subjects participated in the study. A receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value and accuracy. The areas under ROC curves for nitrite/nitrate and AFP were calculated to be 0.758 and 0.812, respectively, which were not significantly different. There was no correlation between the concentrations of plasma nitrite/nitrate and serum AFP. The sensitivity, the specificity, and diagnostic efficiency were 79.5, 72.0, and 75.3%, respectively, for nitrite/nitrate, and 74.4, 76.0, and 75.3%, respectively, for AFP. Based on a partial ROC curve, the clinical utility of plasma nitrite/nitrate as a tumor marker approximated that of serum AFP, but exceeded in AFP-negative patients. Indeed, nitrite/nitrate was positive in 70% of AFP-negative HCC patients. The simultaneous determinations of serum AFP and plasma nitrite/nitrate concentrations gave significant improvement in detection of HCC in CLD patients compared with that of serum AFP alone.

Adult↗

PubMed2000

Monkey pulpal response and microtensile bond strength beneath a one-application resin bonding system in vivo.

OBJECTIVES: The aim of this in vivo study was to investigate the biocompatibility and microtensile bond strength of a one-application resin bonding system. METHODS: Class V cavities were prepared on the facial surfaces of 36 intact monkey teeth, and the cavities were restored with an experimental one-application resin bonding system (TOF-1; Tokuyama Corp., Tokuyama, Japan) and a hybrid resin composite (PALFIQUE ESTELITE; Tokuyama Corp., Tokuyama, Japan). Histopathological changes of the restored teeth were evaluated at 3, 30 and 90 days after operation (N = 10). Microtensile bond tests were performed at 3 and 90 days after operation (N = 10). RESULTS: Only two of 30 pulps showed a slight inflammatory cell infiltration. There were no statistically significant differences in the incidence of slight inflammatory cell infiltration among time periods. Bacterial penetration along the cavity walls could not be detected in any specimen. The mean microtensile bond strength at 3 days after operation was 20.6 MPa, and that at 90 days was 14.9 MPa. Differences in bond strengths between the 3 day specimen and the 90 day specimen were statistically significant (p < 0.05). CONCLUSIONS: The one-application resin bonding system exhibited acceptable biologic compatibility to the monkey pulp. Although there were statistically significant differences in bond strengths between the 3 day specimen and the 90 day specimen, this material provided a hermetic seal, eliminating bacterial microleakage.

Acid Etching, Dental↗

PubMed2000

Impaired beta-cell function in the presence of reduced insulin sensitivity determines glucose tolerance status in acromegalic patients.

OBJECTIVE: Abnormal glucose tolerance is often demonstrated in acromegalic patients. Although insulin resistance is a common feature of acromegaly, it remains unclear whether the extent of insulin resistance per se determines the abnormal glucose tolerance. In order to elucidate this issue, we investigated insulin sensitivity and beta-cell function in acromegalic patients. DESIGN: Twenty-four acromegalic patients were studied in comparison with 24 healthy control subjects. To estimate insulin sensitivity and beta-cell function, we used correct homeostasis model assessment (HOMA) model, a computer-solved model. We also investigated the effects of surgical success on both parameters. RESULTS: HOMA insulin sensitivity (HOMA-%S) in the acromegalic patients was 74 +/- 51 (SD)%, significantly lower than that in 24 healthy controls (144 +/- 49%). HOMA-%S in 12 normal glucose tolerance (NGT) patients was 54 +/- 31%, not significantly different from that in impaired glucose tolerance (IGT; n = 11) or diabetes mellitus (DM; n = 1) patients (93 +/- 60%). By contrast, HOMA beta-cell function (HOMA-%beta) in the NGT acromegalic patients was 163 +/- 67%, significantly higher than the IGT/DM acromegalic patients (89 +/- 34%) and the healthy controls (72 +/- 19%). In 11 patients who achieved complete normalization of GH excess after surgery, HOMA-%S significantly increased to control ranges (from 76 +/- 26 to 159 +/- 61%) within 2 weeks after the surgical success. CONCLUSIONS: We conclude that insulin sensitivity is reduced to a similar extent in acromegalic patients with normal glucose tolerance and those with impaired glucose tolerance or diabetes. Compensatory hyperfunction of beta-cells appears to counterbalance the reduced insulin sensitivity in the acromegalic patients with normal glucose tolerance but not in those with impaired glucose tolerance or diabetes.

Acromegaly↗

PubMed2000

Pathophysiological role of cholecystokinin in humans.

Cholecystokinin (CCK) is a major gastrointestinal hormone that plays an important role in stimulation of pancreatic secretion and gall-bladder contraction, regulation of gastrointestinal motility and induction of satiety. Ingestion of fat and protein induces significant increases in plasma CCK. Intraluminal mediators of CCK secretion, luminal CCK releasing factor and diazepam-binding inhibitor, were purified from rat intestinal secretion. These CCK-releasing factors (RF) are secreted tonically by the small intestine and stimulate CCK release. Another kind of CCK-RF named 'monitor peptide' was purified from the rat pancreatic juice that stimulates CCK secretion when introduced into rat intestine. Bile exclusion from the duodenum causes an increase in basal CCK and enhances stimulated plasma CCK release, and bile salt replacement reverses these effects. Thus, the CCK-RF are spontaneously secreted into the intestinal lumen in humans, while the CCK-producing cells are under constant suppression by intraduodenal bile acids. In acute pancreatitis, plasma CCK levels are high in patients with gallstone pancreatitis, but not in patients with pancreatitis from other causes, such as alcoholic and idiopathic pancreatitis. A transient disturbance of bile flow into the duodenum by stones or oedema of the pancreas together with impairment of pancreatic exocrine function might cause the increase in plasma CCK release in gallstone pancreatitis. Patients with chronic pancreatitis with mild to moderate impairment of exocrine function and abdominal pain, had significantly higher plasma CCK concentrations, whereas patients with pancreatic insufficiency had a significantly lower plasma CCK response to a test meal than the healthy subjects. The increased CCK may further aggravate pancreatitis and worsen the prognosis of pancreatitis by stimulating the injured pancreas, resulting in the vicious circle via endogenous CCK release. The CCK-A receptor antagonist might be therapeutically useful in acute pancreatitis by stopping the vicious circle.

Acute Disease↗

PubMed2000

Troglitazone prevents fatty changes of the liver in obese diabetic rats.

BACKGROUND AND AIMS: Troglitazone is a newly developed antidiabetic drug and is indicated to be useful for the treatment of patients with type II diabetes mellitus. Recently, however, it became clear that troglitazone could cause liver dysfunction in some patients. In addition, a relationship between the activation of the peroxisome proliferator-activated receptor gamma receptor by troglitazone and colon tumorigenesis has been suggested. The present study was undertaken to examine the effects of long-term administration of troglitazone on the liver and intestine in genetically obese and diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) and control Long-Evans Tokushima Otsuka (LETO) rats. METHODS: A troglitazone-rich diet (200 mg/100 g normal chow) or a standard rat chow, free of troglitazone (control), was given to OLETF and LETO rats from 12 or 28 weeks of age until 72 weeks of age. Serum levels of glucose, insulin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined at several time points. In addition, histology of the liver and intestine and serum levels of cholesterol and triglycerides were examined at 72 weeks of age. RESULTS: Troglitazone prevented age-related increases in fasting glucose and insulin concentrations in OLETF rats, but had no significant influences on serum levels of AST and ALT in both strains of rats. The liver weights in the control OLETF rats were significantly heavier than in the LETO rats. Troglitazone significantly reduced serum cholesterol and triglyceride levels and the liver weight. However, it had no influence on the large intestine weight and the number of colonic polyps in both OLETF and LETO rats. Sections of the liver from the untreated OLETF rats showed mild fatty changes in the central zone of the hepatic lobule, whereas those from the troglitazone-treated OLETF rats appeared normal with no fat deposition in the hepatocytes. Troglitazone in LETO rats also caused no significant histopathologic changes of the liver tissue. CONCLUSION: Our present study demonstrated that long-term administration of troglitazone prevents the progress of the metabolic derangement and fatty changes of the liver in genetically determined obese diabetes.

Age Factors↗

PubMed2000

Troglitazone prevents and reverses dyslipidemia, insulin secretory defects, and histologic abnormalities in a rat model of naturally occurring obese diabetes.

Troglitazone has been shown to improve insulin sensitivity and thereby exert hypoglycemic effects in various animal models and humans with insulin resistance and diabetes. The recently established animal model of naturally occurring obese diabetes, the Otsuka Long-Evans Tokushima fatty (OLETF) rat, has many similarities with human type 2 diabetes mellitus and is characterized by a high degree of insulin resistance. In the present study, we examined the effect of pharmacologic intervention with troglitazone on metabolic and histopathologic changes in OLETF rats. Two groups of rats received a troglitazone-rich diet (200 mg/100 g normal chow) from age 12 weeks (ie, before the onset of diabetes) or 28 weeks (ie, after the onset of diabetes) to age 70 weeks, while a third group received standard rat chow. The addition of troglitazone to the diet did not alter food intake or body weight gain. Troglitazone had no influence on visceral adipose depots, but it significantly reduced fasting glucose, insulin, cholesterol, triglyceride (TG), and free fatty acid (FFA) levels. Troglitazone reduced the insulin resistance and maintained the postglycemic insulin response at a normal level, and thus inhibited the development of insulin insensitivity and frank diabetes in OLETF rats up to 70 weeks of age. The pancreatic wet weight and insulin content were significantly higher in the treated rat groups versus the control rats. The morphologic changes observed in the control rats, such as fibrosis and structural disarrangement of islets, were minimal in the troglitazone-treated rats. Our study demonstrates that troglitazone, albeit at a dosage 10 to 15 times higher than that in humans, not only prevents but also reverses the metabolic derangement and histopathologic changes in genetically determined obese diabetes.

Adipose Tissue↗

PubMed2000

Polypoid metastatic hepatocellular carcinoma of the esophagus occurring after endoscopic variceal band ligation.

This report describes a rare case of metastatic hepatocellular carcinoma (HCC) presenting as a polypoid mass in the lower esophagus after endoscopic variceal band ligation (EVL). A 56-year-old man underwent EVL for variceal bleeding in September 1993. He presented with dysphagia and tarry stool in December 1993. An endoscopic examination revealed a semipedunculated polypoid mass at the lower part of the esophagus, where EVL had been performed 3 months previously. The histologic examination at autopsy revealed that the polypoid mass consisted of metastatic HCC that had spread via the retrograde portal flow.

Biopsy↗

PubMed2000

In vitro activity of DU-6681a, an active form of the new oral carbapenem compound DZ-2640, in comparison with that of R-95867, faropenem and oral cephalosporins.

We compared the in vitro antibacterial activity of DU-6681a against Gram-positive and Gram-negative bacteria with that of R-95867, faropenem and oral cephalosporins such as cefcapene, cefotiam and cefpodoxime. DU-6681a is an active form of the new oral carbapenem compound DZ-2640, which is an ester-type prodrug, and R-95867 is an active form of the oral carbapenem CS-834. Against most Gram-positive bacteria, DU-6681a was as active as or two- to 16-fold more potent than R-95867 and faropenem in terms of MIC(90), and comparable to or two- to 64-fold more effective than the cephalosporins. Against most Gram-negative bacteria, the activity of DU-6681a was the same as or two- to 16-fold more potent than that of R-95867, and comparable to or two- to 2048-fold higher than that of faropenem and the cephalosporins.

Administration, Oral↗

PubMed2000

Beta1 integrins play an essential role in adhesion and invasion of pancreatic carcinoma cells.

To investigate the role of beta1 integrins in pancreatic carcinoma invasion, we analyzed the relationship between the activity of beta1 integrins and the invasive ability of human pancreatic carcinoma cell lines. AsPC1, BxPC3, PANC1, SU8686, KP1NL, KP2, and H48N cells had high expression of beta1 and alpha6 subunits, and various levels of alpha2, alpha3, and alpha5 expression as determined by flow cytometry. Cell adhesion assay revealed that alpha2beta1, alpha5beta1, and alpha6beta1 integrins were the predominant adhesion receptors for collagen, fibronectin, and laminin, respectively. Beta1 integrins on different cell types showed a wide range of constitutive activity. Anti-beta1 monoclonal antibody (MAB) TS2/16 rapidly activated beta1 integrins, and thus TS2/16 requirement in cell adhesion represented the levels of constitutive activity of beta1 integrins. Notably, as the result of in vitro chemoinvasion assay, the levels of constitutive activity of beta1 integrins correlated with the invasive ability of pancreatic carcinoma cells. The inhibitory anti-beta1 MAB 13 completely blocked the invasion of these cell lines. Alternatively, the stimulatory anti-beta1 MAB TS2/16 strongly inhibited the invasion. These results show an essential role of beta1 integrins in invasion of pancreatic carcinoma cells and also suggest subtle regulatory mechanisms of cell invasion.

Antibodies, Monoclonal↗

PubMed2000

[Report of questionnaire survey for methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae in the Kinki District].

An epidemiological investigation for methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae (PRSP) was performed at 22 medical institutes in Kinki area by the questionnaire from Kinki Infection Working Group in 1998. The isolation frequencies of MRSA and PRSP, including penicillin-intermediate resistant S. pneumoniae (PISP), were 61.5 and 45.8%, respectively. As compared to the previous data of MRSA in the Kinki area of 1997, the increase of MRSA was recognized. A single infection with MRSA was 49.5% and simultaneous pathogen detected with MRSA was Candida species. On the other hand, a single infection with PRSP including PISP, was 36.4% and simultaneous pathogen with PRSP was Haemophilus influenzae. Vancomycin, teicoplanin, ST and arbekacin showed good activity against MRSA. PRSP and PISP had low activity to ampicillin and erythromycin.

Humans↗

PubMed2000

Improved synthesis of paroxetine hydrochloride propan-2-ol solvate through one of metabolites in humans, and characterization of the solvate crystals.

Paroxetine, a potent and selective inhibitor of 5-hydroxytryptamine (serotonin) uptake, was prepared through a piperidine derivative, which was reported to be one of the paroxetine metabolites in humans. Thus, the piperidine derivative was converted to its N-tert-butoxycarbonyl (N-Boc) derivative, which was then converted to N-Boc paroxetine. Paroxetine hydrochloride propan-2-ol (isopropyl alcohol (IPA)) solvate crystals were directly obtained from the N-Boc paroxetine by adding hydrogen chloride to the N-Boc paroxetine IPA solution. The amount of IPA content in the crystals was reduced by drying with a continuous change of powder X-ray diffraction patterns. Other characterizations of the solvate crystals were also conducted.

Crystallography, X-Ray↗