Clinical benefits of routine examination and synchronous repair of occult inguinal hernia during laparoscopic peritoneal dialysis catheter insertion: a single-center experience.

PURPOSE: Occult inguinal hernias (IH) predispose peritoneal dialysis (PD) patients to the symptomatic IH formation after starting PD, which may cause complications. We conducted a retrospective study to assess the benefit/risk profile of routine laparoscopic examination for occult IH (RLEOH) with a synchronous repair in patients receiving PD catheter placement. METHODS: 432 patients were enrolled in this study. Patients with an internal hernia sac at all sizes were deemed to have occult IH. We retrospectively reviewed data including demographic characteristics and operative details. We also measured incidence rates of symptomatic IH, metachronous IH repair, and catheter survival over a follow-up period after starting PD. RESULTS: These patients were classified into the RLEOH group (n = 365) and the non-RLEOH group (n = 67). The RLEOH group was subdivided into occult IH with a synchronous repair (n = 17; the subgroup A), no occult IH (n = 339; the subgroup B), and occult IH without a synchronous repair (n = 9; the subgroup C). The incidence rates of symptomatic IH developed after staring PD in subgroups A, B, and C were 0, 5.6, and 22.2%, respectively, whereas that in the non-RLEOH group was 13.4%. The RLEOH group had a reduced hazard ratio for metachronous IH repair compared with the non-RLEOH group (HR = 0.426; 95% CI 0.195-0.930, p = 0.032). None of our patients suffered from herniorrhaphy-related complications. CONCLUSION: RLEOH with a synchronous repair during PD catheter insertion confers clinical benefits in reducing the risk of developing IH after starting PD and the need for a metachronous repair. This is a safe and reasonable approach.

Spleen-preserving versus spleen-sacrificing distal pancreatectomy in adults with blunt major pancreatic injury.

BACKGROUND: The aim of this study was to analyse outcomes of spleen-preserving (SPDP) and spleen-sacrificing (SSDP) distal pancreatectomy in adults with severe blunt pancreatic injuries. METHODS: This was an observational study of adult patients who underwent distal pancreatectomy for grade III or IV blunt pancreatic injury between 1991 and 2015. Outcomes of SPDP and SSDP were compared. RESULTS: Fifty-one patients were included, of whom 23 underwent SPDP and 28 SSDP. The median Injury Severity Score (ISS) was 13·0 (i.q.r. 9·0-18·0). No significant differences were observed between the groups regarding sex, trauma mechanism, shock at triage, laboratory data, location, ISS, associated injury, length of stay, mortality or morbidity. Age (27·0 versus 36·5 years; P = 0·012) and time interval from injury to distal pancreatectomy (15·0 versus 44·0 h; P = 0·022) differed significantly between SPDP and SSDP groups respectively. The mortality rate was 4 per cent (1 of 23) versus 11 per cent (3 of 28) respectively (P = 0·617). Nine patients (39 per cent) developed abdominal morbidity after SPDP, compared with 17 (61 per cent) after SSPD (P = 0·125). In the SPDP group, eight patients had grade B postoperative pancreatic fistula (POPF), two of whom required further intervention. In the SSDP group, six of ten patients with grade B POPF required CT-guided drainage, and a further five patients required reoperation for other causes. There were more reinterventions after SSDP: 11 of 28 (39 per cent) versus 3 of 23 (13 per cent) in the SPDP group (P = 0·037). CONCLUSION: SPDP was performed more often in younger patients and at a shorter interval after severe blunt pancreatic injury. SPDP was associated with fewer reinterventions.

Prognostic significance of the number of examined lymph nodes in node-negative gastric adenocarcinoma.

AIM: In this study, we investigated the prognostic significance of the number of examined lymph nodes in node-negative gastric adenocarcinoma (GC). PATIENTS AND METHODS: A total of 1194 node-positive and 1030 node-negative GC patients undergoing potentially curative gastrectomy was enrolled in this study. Patients were stratified into 3 groups according to the number of examined lymph nodes: group 1, ≤ 15; group 2, 16-25; group 3, >25. RESULTS: Patients with node-negative GC had significantly favorable survival compared with those with node-positive. Among patients with node-negative T2-T4 disease, the percentage of locoregional relapse was higher in those with <25 examined lymph nodes than in those with ≥ 25 examined lymph nodes. The number of examined lymph nodes affected the overall survival rates for patients with node-negative T2-T4 GC but not for patients with T1 lesions. Tumor size, tumor location, the number of examined lymph nodes, T status, and the presence of perineural invasion were significant prognostic factors as determined by multivariate analysis in node-negative GC. CONCLUSIONS: No survival benefit of examining ≥ 15 lymph nodes was noted for patients with node-negative T1 GC. Extensive lymphadenectomy in patients with node-negative T2-T4 lesions in whom the number of examined lymph nodes was >25 had favorable survival.

Candida parapsilosis peritonitis complicated with infected pancreatic pseudocysts in a peritoneal dialysis patient: a challenge for nephrologists.

In continuous ambulatory peritoneal dialysis (CAPD)-related cases of fungal peritonitis, Candida parapsilosis (C. parapsilosis) has become as common as Candida albicans (C. albicans) in fungal isolates. This report describes a 74-year-old male CAPD patient who received bypass surgery for coronary artery disease, followed by an episode of bacterial peritonitis. The peritonitis was successfully treated with intraperitoneal antibiotics. However, C. parapsilosis peritonitis with concomitant pancreatitis and infected pseudocysts occurred one month later. Despite surgical drainage and intravenous administration of fluconazole, fungal peritonitis persisted. Finally, he died of nosocomial pneumonia. This case demonstrates the poor outcome of C. parapsilosis peritonitis, suggesting a more aggressive treatment in peritoneal dialysis patients.

Transdermal delivery of tea catechins by electrically assisted methods.

Tea polyphenols, including (+)-catechin, (-)-epicatechin, and (-)-epigallocatechin-3-gallate (EGCG), have been shown to possess potent antioxidant and chemopreventive activities. The aim of this study was to assess the effects of electroporation, iontophoresis, and their combination on the transdermal delivery of tea catechins across porcine skin. The permeation characteristics were investigated using various analogues of catechins, pH values, and modes of electroporation and iontophoresis. The mechanisms by which these catechins were transported via the skin were elucidated by examining the electric conductivity, transepidermal water loss (TEWL), and fusion of stratum corneum lipid liposomes (SCLL). The isomers, (+)-catechin and (-)-epicatechin, showed different behaviors of skin permeation and local skin deposition with the electrically assisted methods. The results suggest evidence of selective skin absorption of (-)-epicatechin over (+)-catechin. A synergistic effect was detected for (+)-catechin but not for (-)-epicatechin after application of electroporation followed by iontophoresis. The presence of a gallic acid ester in the structure of EGCG significantly increased the skin uptake of catechins. However, a negligible amount of or no EGCG molecules permeated across the skin. The mechanisms involved in the enhancement of electroporation may be the skin reservoir effect and an increase in skin permeability. The TEWL profiles suggest that in addition to the force of electrorepulsion, the skin hydration effect and structural alterations may also have contributed to the enhancement by iontophoresis. Electroporation did not influence the skin barrier function, although the skin permeability increased according to the SCLL fusion study.

Selective cytotoxicity of azatyrosinamides against ras-transformed NIH 3T3 cells.

This study aims to develop novel azatyrosinamide compounds structurally modified from ras-specific antioncogenic azatyrosine. Analogues 4-15 were prepared and their inhibition on the growth of wild-type and ras-transformed NIH 3T3 cell lines was compared. Compound 12 was found to be the most active with IC50 16.5+/-2.2 microM which is 458-fold more potent than that of azatyrosine. The selective toxicity, defined as IC(50 wild-type)/IC(50 ras-transformed) for this compound was 138.5.

Analysis of sonographic features for the differentiation of benign and malignant breast tumors of different sizes.

OBJECTIVE: To analyze the value of various sonographic features in differentiating benign from malignant breast tumors of different sizes to improve the diagnostic accuracy in small lesions. METHODS: The sonographic features of 1203 histologically confirmed solid breast lesions were prospectively documented with respect to anteroposterior (AP) diameter/width ratio, shape, margin, echogenicity, echotexture, posterior echo and bilateral refraction sign. The sensitivity, specificity and accuracy of breast ultrasound were calculated for lesions grouped according to size (< or = 1, 1.1-2 and > 2 cm). Univariate and multiple logistic regression analyses including calculation of odds ratios for single sonographic features were used to analyze the significance of the different diagnostic features. RESULTS: The accuracy of breast sonography in differentiating between benign and malignant tumors < or = 1, 1.1-2 and > 2 cm in size was 75.6%, 86.4% and 88.4%, respectively. Univariate analysis demonstrated that all sonographic features were significant in tumors > or = 1.1 cm. Shape, margin, echogenicity and echotexture were the significant factors in those tumors < or = 1 cm. Multiple logistic regression analysis demonstrated that margin, shape, posterior echo and echogenicity were the significant factors for differential diagnosis in tumors > 2 cm. Echogenicity, margin, shape, bilateral refraction sign and echotexture were the significant factors for tumors 1.1-2 cm. On multiple regression analysis, margin was the only significant factor for tumors < or = 1 cm. CONCLUSION: Tumor margin is the most important sonographic feature in evaluating breast lesions in any size group. With the combination of significant factors and emphasis on specific features according to size of lesion, the diagnostic accuracy of ultrasound for the differential diagnosis of malignant and benign tumors may be improved.

Sonographic differentiation of invasive and intraductal carcinomas of the breast.

The purpose of this study is to evaluate the diagnostic ability of ultrasound and define the sonographic features of symptomatic intraductal and invasive breast carcinoma. To achieve this the ultrasound features of 488 invasive carcinomas and 65 non-screening detected intraductal carcinomas were compared retrospectively. The features included size, AP/W (anteroposterior diameter/width) ratio, shape, margin, internal echogenicity, internal echotexture, posterior acoustic transmission, bilateral edge shadowing sign and calcifications. The sensitivity and specificity of the detection of calcifications by ultrasound in comparison with mammography were also studied. The accuracy of ultrasound diagnosis is 92.0% for invasive carcinoma of breast and 84.8% for intraductal carcinoma. Differentiation of ultrasound features of intraductal and invasive carcinoma can be based on the internal hypoechogenicity, loss of bilateral edge shadowing, posterior acoustic transmission, irregular shape and non-uniform internal echotexture with odds ratio of 0.3, 0.3, 0.4, 0.5 and 0.5, respectively. Internal echogenicity was the only significant differentiating factor on multiple logistic regression analysis. Non-comedo type ductal carcinoma in situ can be differentiated from comedo type by irregular shape with odds ratio of 0.3. The sensitivity, specificity and accuracy rate for the detection of calcifications in invasive carcinomas by ultrasound were 65.1%, 61.9% and 63.2%; in comedo type intraductal carcinoma 62.5%, 66.7% and 63.6%, and in non-comedo type intraductal carcinoma 30.0%, 86.7% and 64.0%, respectively. The ultrasound appearance of non-screening detected intraductal carcinoma is relatively isoechoic in comparison with invasive carcinoma. More than 60% of microcalcifications in comedo type intraductal carcinoma can be accurately demonstrated by ultrasound. However, the role of ultrasound in detecting symptomatic intraductal carcinoma warrants further study.

Characterisation of oestrogen receptor, progesterone receptor, trefoil factor 1, and epidermal growth factor and its receptor in pancreatic cystic neoplasms and pancreatic ductal adenocarcinoma.

BACKGROUND AND AIMS: The pancreatic cystic neoplasms, including solid pseudopapillary tumour (SPT), mucinous cystic neoplasm (MCN), and intraductal papillary mucin producing tumour (IPMT), have their characteristic clinicopathological features. A systematic investigation of oestrogen receptor (OR), progesterone receptor (PR), trefoil factor 1(TFF1), and epidermal growth factor and its receptor (EGF and EGFR) expressed in pancreatic cystic neoplasms and pancreatic ductal adenocarcinoma was determined to elucidate their corresponding sex and age predilection, cell origin, and pathway of malignant transformation. METHODS: Surgical specimens of SPT (n=10), MCN (n=12), IPMT (n=10), and ductal adenocarcinoma (n=20) were studied. The expression of OR, PR, TFF1, EGF, and EGFR were each determined in each disease entity using monoclonal antibodies by immunohistochemical method. The results were correlated with the clinicopathological data. RESULTS: PR was expressed in all 10 SPT, whereas OR was expressed in none of 10 SPT. TFF1 was not or weakly expressed in SPT. Although EGF was strongly expressed in seven of 10 SPT, synchronous expression of EGF and its receptor was expressed in none of 10 SPT. Of the 12 MCN, six had PR expression in the stroma cells but not in the neoplastic epithelium, seven had a moderate or strong expression of TFF1, and 10 had no or weak EGFR expression, irrespective of their benigneity or malignancy. Synchronous expression of EGF and EGFR was observed in only one of 12 MCN. Among 10 IPMT, TFF1 and EGFR were moderately or strongly expressed in all six malignancies, whereas TFF1 and EGFR were not or weakly expressed in three of four benigneity. Of 20 ductal adenocarcinomas, TFF1 and EGFR were moderately or strongly expressed in 16 and 12, respectively. Synchronous expression of EGF and EGFR was observed in six of 10 IPMT and nine of 20 ductal adenocarcinoma, respectively. CONCLUSION: PR was uniquely expressed in SPT, and OR and PR were expressed in stroma of MCN, reflecting their sex and age predilection. TFF1 expression was related to EGFR such as in IPMT and ductal adenocarcinoma, not related to EGFR such as in MCN, and not related to hormonal receptors such as in SPT. EGF and its receptor might play a part in the malignant transformation of IPMT and ductal adenocarcinoma, but not of SPT and MCN.

Parenteral nutrition support after bone marrow transplantation: comparison of total and partial parenteral nutrition during the early posttransplantation period.

OBJECTIVE: Bone marrow transplantation (BMT) usually is indicated if the patient's malignant disease involves the marrow or if hazard to the normal marrow is the limiting factor in the aggressive treatment of disease. The success of BMT depends on a complete team with all the resources needed to ensure optimal results. Aggressive nutrition support after BMT is very important. Adequate parenteral nutrition, total (TPN) or partial, followed by enteral nutrition according to the patient's gastrointestinal function is the important principle. METHODS: Between 1996 and 2000, 60 patients, 46 male and 14 female, received BMT in Chang Gung Memorial Hospital. Their ages ranged from 6 to 54 y. Standard TPN was used in 40 patients after BMT, and partial parenteral nutrition was used in the remaining 20 patients. TPN was enriched with branched-chain amino acids (BCAA) when the patient's liver functions were impaired, and cyclic TPN was shifted when the patient's liver functions persistently deteriorated. RESULTS: Most patients improved their nutrition status and increased their body weights, especially those receiving TPN. The patients receiving partial parenteral nutrition decreased their visceral proteins significantly during the course of parenteral nutrition. The BCAA-TPN can maintain a patient's visceral protein better than standard TPN. Only two patients expired because of graft rejection and sepsis; their body weights and nutrition status showed deterioration despite aggressive nutrition support. CONCLUSIONS: We conclude that the nutrition support for patients with BMT is related to the success of marrow transplantation. Parenteral nutrition support, especially with TPN, is important because of frequent gastrointestinal dysfunction during the posttransplantational period, and it is better at maintaining the nutrition status and body weights of patients after BMT. An oral diet can be resumed after the patient's gastrointestinal function has improved and it can be tolerated.

Inhibition of the expression of inducible nitric oxide synthase and cyclooxygenase-2 in macrophages by 7HQ derivatives: involvement of IkappaB-alpha stabilization.

Nitric oxide is an important biological mediator associated with multiple pathophysiological phenomena, such as platelet aggregation, vasodilation, septic shock, and autoimmune diseases. Prostaglandins, derived from cyclooxygenases, play prominent roles in homeostasis and inflammation. In this study, we characterized the effects of 7HQ derivatives (7-[(4-methylene-5-oxo-2-R-2-tetrahydrofuranyl) methoxy]-3,4-dihydrocarbostyril, where R is methyl, phenyl, p-fluorophenyl and p-phenylphenyl; 7HQ-1,-2,-3 and-4, respectively) in murine RAW 264.7 cells, a macrophage-like cell line. Lipopolysaccharide, the active component of endotoxin, significantly induced the expression of inducible nitric oxide synthase and cyclooxygenase-2, leading to the accumulation of nitrite and prostaglandin E(2), respectively. These actions of lipopolysaccharide were inhibited by 7HQ derivatives; additionally, the inhibition of the expression, rather than the activity, of inducible nitric oxide synthase correlated well with that of nitric oxide formation. Western blotting and electrophoretic mobility shift assay results demonstrated that the 7HQ derivatives could effectively inhibit IkappaB-alpha degradation and nuclear factor kappaB (NF-kappaB) translocation. At higher concentrations, 7HQ derivatives also inhibited cyclooxygenase-2 enzyme activity. These results suggest that 7HQ derivatives exhibit inhibitory effects on lipopolysaccharide-induced nitric oxide production and expression of inducible nitric oxide synthase and cyclooxygenase-2 through inhibition of IkappaB-alpha degradation and NF-kappaB activation.

Human progesterone receptor shows differential sensitivity to carboxyl group modifying agents when bound to agonist and antagonist ligands.

BACKGROUND: Modulation of human uterine progesterone receptor (PR) in relation to its binding to synthetic steroids with known agonist (R5020) and antagonist (triamcinolone acetonide, T.A.) properties was studied in the presence of the specific carboxyl group modifiers, N,N'-dicyclohexylcarbodiimide (DCCD) and 1-ethyl-3-carbodiimide hydrochloride (EDC). METHODS: Uterine cytosol was treated with DCCD or EDC. The amounts of total bound were detected using the steroid binding measurements. The formation and transformation of progesterone-receptor complexes (PRc) were analyzed using sedimentation rate analysis. RESULTS: Our studies show that the modification of the COOH group differentially influences the properties of mammalian PR binding with either R5020 or T.A. DCCD and EDC affect the steroid binding of PR by decreasing the binding sites, not by the changing the affinity. CONCLUSION: Our studies indicate the importance of the carboxyl group in steroid binding by PR. This implies that both aspartic acid and glutamic acid residues, which have the carboxyl group, may play an important role when PR binds with steroid ligands.

Inhibitory effect of DCDC on lipopolysaccharide-induced nitric oxide synthesis in RAW 264.7 cells.

In the present study we have examined the effect of DCDC (2',5'-dihydroxy-4-chloro-dihydrochalcone) on lipopolysaccharide (LPS)-induced responses in murine macrophage cell line RAW 264.7. Exposure of LPS-stimulated cells to DCDC inhibited the nitrite accumulation in culture medium. DCDC also concentration-dependently inhibited LPS-stimulated increase of iNOS expression; however, it had little effect on iNOS enzyme activity, suggesting that the inhibitory action to DCDC is mainly due to the inhibition on iNOS expression rather than iNOS enzyme activity. DCDC significantly inhibited LPS-evoked degradation of IkappaB-alpha and the nuclear translocation of NF-kappaB; it also exhibited the activity of scavenging the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH). DCDC also inhibited cyclooxygenase-2 activity in RAW 264.7 cells with an IC50 of 3.0 microM; furthermore, it also significantly decreased LPS-induced mortality rate in mice. Taken together, we demonstrate that DCDC exhibits inhibitory effects on nitric oxide production through the inhibition of IkappaB-alpha degradation and NF-kappaB activation, and therefore the suppression of iNOS expression. DCDC also shows the antioxidant activity and COX-2 inhibitory action. Moreover, it improves survival in a murine model of endotoxaemia suggesting that DCDC may be potential in the therapy of septic shock.

Surgery for chronic obstructive pancreatitis: comparison of end-to-side pancreaticojejunostomy with pancreaticoduodenectomy.

BACKGROUND/AIMS: Chronic obstructive pancreatitis usually manifests with intractable pain and recurrent episodes of chronic pancreatic inflammation. The side-to-side pancreaticojejunostomy is used for those patients with a large pancreatic duct. But for the patients with small pancreatic duct, the optimal surgical procedure needs to be evaluated. A prospective study was designed to compare the different results between distal pancreatectomy plus end-to-side pancreaticojejunostomy and pancreaticoduodenectomy. METHODOLOGY: The patients were chosen prospectively and randomly to undergo either a distal pancreatectomy plus end-to-side pancreaticojejunostomy or pancreaticoduodenectomy in the last 3 years. Eighteen patients with chronic obstructive pancreatitis were randomly divided into two groups. Ten patients (group A) underwent distal pancreatectomy plus end-to-side and ductal to mucosal pancreaticojejunostomy, and the other 8 patients (group B) underwent pancreaticoduodenectomy were compared. RESULTS: The operative time was significantly shorter and operative blood loss was less in group A. The postoperative follow-up of patients in group A had better outcome with increased body weight and no steatorrhea or diabetes mellitus, and all of them had complete pain relief. CONCLUSIONS: We concluded that distal pancreatectomy with end-to-side pancreaticojejunostomy provided a better surgical treatment for the patients with chronic obstructive pancreatitis and small pancreatic duct.

Early use of cyclic TPN prevents further deterioration of liver functions for the TPN patients with impaired liver function.

BACKGROUND/AIMS: Impaired liver function is frequently found in patients who need prolonged total parenteral nutrition. Cyclic total parenteral nutrition can minimize the adverse effects of long-term total parenteral nutrition, such as hepatic complication. The adequate timing to shift to use cyclic total parenteral nutrition for patients with impaired liver function may prevent further hepatic dysfunction. METHODOLOGY: A prospective study of 65 patients who need total parenteral nutrition and have impaired liver functions was performed. Cyclic total parenteral nutrition was used in different groups of patients, when their total bilirubin levels were just over 5 mg%, 10 mg%, or 20 mg% during the course of total parenteral nutrition. The patients of control groups received straight non-cyclic total parenteral nutrition. All the patients had stable vital signs without major stress, such as sepsis or acute bleeding. Ten patients (A2) in Group A were shifted to cyclic total parenteral nutrition when their total bilirubin was just over 5 mg%; the other 10 patients (A1) continued the non-cyclic total parenteral nutrition. Eleven patients (B2) in Group B were shifted to cyclic total parenteral nutrition when their total bilirubin was just over 10 mg%; the other 11 patients (B1) continued the non-cyclic total parenteral nutrition. Ten patients (C2) in Group C were shifted to cyclic total parenteral nutrition when their total bilirubin was just over 20 mg%; the other 13 patients (C1) continued the non-cyclic total parenteral nutrition. The average energy intake among 3 groups had no difference. Their liver functions were examined each week for 2 weeks. RESULTS: The results showed that the patients with non-cyclic total parenteral nutrition had significant increase of direct-total bilirubin and alkaline phosphatase (P < 0.05) in Group A and significant decrease of albumin accompanied with increase of GOT, GPT, direct/total bilirubin (P < 0.05) in Group B. The patients either using cyclic or non-cyclic total parenteral nutrition showed significant decrease of albumin and increase of direct/total bilirubin (P < 0.05) in Group C. CONCLUSIONS: We conclude that the early use of cyclic total parenteral nutrition may prevent deterioration of liver function for the patients with jaundice and need prolonged total parenteral nutrition.

Prospective and randomized study of gabexate mesilate for the treatment of severe acute pancreatitis with organ dysfunction.

BACKGROUND/AIMS: Exaggerated production of various proteases may account for the late presence of organ dysfunction in acute pancreatitis. This study examined the effects of early administration of gabexate mesilate on the condition of patients with severe acute pancreatitis and organ dysfunctions. METHODOLOGY: Fifty-two patients with acute pancreatitis and organ dysfunction were enrolled. The treatment group included 26 patients receiving intravenous gabexate mesilate infusion at a dose of 100 mg/hr for 7 days. APACHE-II score, clinical and biochemical parameters were monitored intensively. RESULTS: Coagulopathy ileus, and abdominal pain was significantly improved with gabexate mesilate. Gabexate mesilate reduced the necessity for surgical intervention and peritoneal lavage. The 7-day-mortality and 90-day-mortality rates were also significantly reduced with gabexate mesilate therapy. CONCLUSIONS: There are strong indications from this study that early intravenous gabexate mesilate infusion results in improved survival in acute pancreatitis with organ dysfunctions.

YD-3, a novel inhibitor of protease-induced platelet activation.

1. In the present study, the antiplatelet effects and mechanisms of a new synthetic compound YD-3 [1-benzyl-3(ethoxycarbonylphenyl)-indazole] were examined. 2. YD-3 inhibited the aggregation of washed rabbit platelets caused by thrombin (IC(50)=28.3 microM), but had no or little inhibitory effect on that induced by arachidonic acid, collagen, platelet-activating factor (PAF) or U46619. YD-3 also suppressed generation of inositol phosphates caused by thrombin. On the other hand, thrombin-induced fibrin formation was not affected by YD-3, indicating YD-3 does not inhibit the proteolytic activity of thrombin. 3. In washed human platelets, however, YD-3 had only mild inhibitory effect on the low concentration (0.05 u ml(-1)) of thrombin-induced human platelet aggregation, and did not affect that induced by higher concentrations (> or =0.1 u ml(-1)) of thrombin or SFLLRN, the protease-activated receptor 1 (PAR1) agonist peptide. By contrast, YD-3 inhibited both human and rabbit platelet aggregation elicited by trypsin with IC(50) values of 38.1 microM and 5.7 microM, respectively. 4. YD-3, at 100 microM, had no effect on ristocetin-induced glycoprotein Ib (GPIb)-dependent aggregation of human platelets. In addition, platelets treated with chymotrypsin, which cleaves GPIb, enhanced rather than attenuated the inhibition of YD-3 on thrombin-induced human platelet aggregation. These data indicate that GPIb plays no role in the antiplatelet effect of YD-3. 5. In SFLLRN-desensitized human platelets, high concentration of thrombin (1 u ml(-1)) could still elicit intracellular Ca(2+) mobilization, and the rise of [Ca(2+)](i) was prevented by either leupeptin or YD-3. 6. Our results suggest that YD-3 inhibits a non-PAR1 thrombin receptor which mediates the major effect of thrombin in rabbit platelets, but in human platelets, this receptor function becomes significant only when the function of PAR1 has been blocked or attenuated.

Pharmacological characterization of EK112, a new combined angiotensin II and thromboxane A(2) receptor antagonist.

The pharmacological characterization of EK112, a new combined angiotensin II and thromboxane A(2) receptor blocking agent, was examined in this study. EK112 was found to be a angiotensin II receptor antagonist, as revealed by its competitive antagonism of angiotensin II-induced smooth muscle contraction (pA(2) value of 7. 63 +/- 0.14) in rabbit aorta. It also had an angiotensin II blocking action in guinea pig ileum (pA(2) value of 7.87 +/- 0.67). Additionally, EK112 also possessed thromboxane A(2) receptor blocking activity, since it competitively antagonized aortic contractile responses elicited by U46619 and PGF(2alpha)(pK(B) values of 6.67 +/- 0.09 and 6.24 +/- 0.09, respectively) in rat. In contrast, EK112 did not affect the contractile responses to many other receptor agonists. EK112 did not mimic that of the angiotensin-converting enzyme (ACE) inhibitor, captopril, to enhance the muscle contraction elicited by bradykinin in guinea pig ileum, suggesting that EK112 did not inhibit ACE. Neither cyclic AMP nor cyclic GMP content in rat aortic rings was changed by EK112. These data demonstrate that EK112 is a selective antagonist of angiotensin II > thromboxane A(2) thromboxane A(2) receptor.

Impact of concomitant hepatolithiasis on patients with peripheral cholangiocarcinoma.

The association of hepatolithiasis (HL) and peripheral cholangiocarcinoma (PCC) has been well recognized. However, information concerning the impact of hepatolithiasis on patients with peripheral cholangiocarcinoma is sparse and therefore difficult to assess. A total of 162 consecutive patients with histologically proven peripheral cholangiocarcinoma were treated surgically at Chang-Gung Memorial Hospital between 1977 and 1994. Among them, 106 patients (65.4%) had associated hepatolithiasis (PCC + HL group), and the remaining 56 patients (34.6%) did not (the PCC - HL group). The differences in demographics, symptomatology, laboratory data, tumor staging, histological pattern, resectability rates, and long-term survival of these two groups were compared. The male to female ratio was 0.7 in the PCC + HL group and 1.3 in the PCC - HL group (P < 0.05). Two thirds of the PCC + HL group presented with acute cholangitis, whereas two thirds of the PCC - HL group presented with hepatomegaly (P < 0.01). Those patients in the PCC + HL group were in earlier stages than those of the PCC - HL group at the time of the initial diagnosis (P < 0.05). The resectability rate for the PCC + HL group was 31.1% and for the PCC - HL group, 26.8% (P > 0.05). Surgical mortality rates were 3.8% in the PCC + HL group and 3.6% in the PCC - HL group (P > 0.05). The morbidity rate was much higher in the PCC + HL group than in the PCC - HL group (P < 0.01). The 1-, 3-, and 5-year survival rates were 35.5%, 20.5%, and 16.5% in the PCC + HL group and 27.2%, 8.8%, and 7.8% in the PCC - HL group (P > 0.05). In conclusion, the presence of hepatolithiasis hindered an exact diagnosis of underlying cholangiocarcinoma preoperatively, precipitated biliary sepsis which affected resectability, and increased postoperative morbidity. Hepatolithiasis per se, however, did not influence the long-term survival.

Contrast-enhanced dynamic computed tomography does not aggravate the clinical severity of patients with severe acute pancreatitis: reevaluation of the effect of intravenous contrast medium on the severity of acute pancreatitis.

BACKGROUND: Contrast-enhanced abdominal computed tomography (CT) is useful in demonstrating pancreatitis necrosis, but the administration of contrast medium in animal models with acute pancreatitis may worsen the severity. HYPOTHESIS: The use of contrast-enhanced CT in clinical patients with acute pancreatitis may actually aggravate the severity of the disease. DESIGN: A randomized prospective study. SETTING: Chang Gung Memorial Hospital, Taipei, Taiwan. PATIENTS: Twenty patients with severe acute pancreatitis were randomly divided into 2 groups. Those in group A (n = 10) underwent a CT examination with a contrast-enhanced medium, and those in group B (n = 10) underwent a CT examination without a contrast-enhanced medium. MAIN OUTCOME MEASURES: The patients' serum amylase, lipase, C-reactive protein, leukocyte, glutamicoxaloacetic transaminase, creatinine, calcium, and phosphate levels were serially checked before the CT examination and at 2, 4, 6, 8, 12, and 24 hours after the examination was performed. The biochemical data between the 2 groups were compared. The morbidity, length of stay, and mortality were also compared. RESULTS: There were no significant changes in the level of pancreatic enzymes, C-reactive proteins, and leukocytes and in the biochemical data of either group before or after the CT examination. The difference in the previously examined values between the 2 groups was also not significant. There was also no difference in the morbidity, length of hospital stay, and mortality between the 2 groups. CONCLUSION: Contrast-enhanced abdominal CT does not aggravate the severity of clinical patients with severe acute pancreatitis.