The use of a mini-laparotomy in total abdominal colectomy for mucosal ulcerative colitis

BACKGROUND/AIMS: Minimally invasive surgery, with its advantages of early return to normal activity and good cosmetic results, is an important goal in the treatment of patients with mucosal ulcerative colitis. The aim of this study was to compare outcomes utilizing a mini-laparotomy approach to total abdominal colectomy for mucosal ulcerative colitis with those of the conventional approach. METHODOLOGY: Eleven patients scheduled to undergo the first (total abdominal colectomy) of a 2 or 3-stage operation for mucosal ulcerative colitis via a mini-laparotomy between 1999 and 2001 were prospectively studied. The mini-laparotomy described here involves total abdominal colectomy performed through a skin incision shorter than 7 cm. Seven similar patients who underwent conventional laparotomy between 1995 and 1998 served as the control group. RESULTS: The mini-laparotomy approach was accomplished in 9 patients (81.8%). Patient characteristics between cases and controls were similar. Postoperative intervals until standing, walking, flatus, urinary catheter removal, and tolerance of solid diet were significantly shorter in the mini-laparotomy group (P = 0.031, P = 0.023, P = 0.0033, P = 0.0093, and P = 0.023, respectively). CONCLUSIONS: A mini-laparotomy approach to total abdominal colectomy appears feasible and safe in selected patient with mucosal ulcerative colitis and poses an attractive alternative to conventional laparotomy in patients similar to those presented here.     

Impact of renal insufficiency on clinical and angiographic outcomes following percutaneous coronary intervention with sirolimus-eluting stents.

BACKGROUND: Sirolimus-eluting stents (SES) have been demonstrated to reduce restenosis. However, there have been few studies evaluating the impact of renal insufficiency on the angiographic as well as clinical outcomes after SES implantation. METHODS: This study was composed of 304 consecutive patients having 361 lesions who underwent percutaneous coronary intervention with SES. The patients were divided into 3 groups according to renal function (group 1 [n = 204]; creatinine clearance (Ccr) > or = 60 ml/min, group 2 [n = 69]; Ccr < 60 ml/min, group 3 [n = 31]; hemodialysis). Clinical and angiographic follow-up were evaluated at 8 months. RESULTS: Clinical follow-up was obtained in all patients and angiographic follow-up was obtained in 283 patients (93.1%). Patients in group 3 showed a higher incidence of previous coronary artery bypass graft surgery, and there were more female gender, hypertensive, and less hyperlipidemia in this group. Late lumen loss at 8 months was significantly different among the 3 groups (group 1; 0.16 +/- 0.46 mm, group 2; 0.44 +/- 0.62 mm, group 3; 0.81 +/- 0.88 mm, P < 0.0001). Major adverse cardiac events (MACE) were documented in 22 patients (10.8%) in group 1, 13 patients (18.8%) in group 2, and 12 patients (38.7%) in group 3, respectively (P = 0.0002). CONCLUSION: Neointimal growth following SES implantation is more pronounced in patients with renal insufficiency, especially those undergoing dialysis, compared with patients with normal renal function. Regardless of the beneficial effect of SES, the increased risk of MACE mainly due to high incidence of target vessel revascularization in the subgroup of patients with renal insufficiency should be taken into account.     

A Comparison of Intravenous Sedation With Two Doses of Dexmedetomidine: 0.2?μg/kg/hr Versus 0.4?μg/kg/hr

The present study investigated the physiologic and sedative effects between two different continuous infusion doses of dexmedetomidine (DEX). Thirteen subjects were separately sedated with DEX at a continuous infusion dose of 0.2 µg/kg/hr for 25 minutes after a loading dose of 6 µg/kg/hr for 5 minutes (0.2 group) and a continuous infusion dose of 0.4 µg/kg/hr for 25 minutes after a loading dose of 6 µg/kg/hr for 5 minutes (0.4 group). The recovery process was then observed for 60 minutes post infusion. The tidal volume, mean arterial pressure, and heart rate in both groups decreased significantly during infusion, but they were within a clinically acceptable level. A Trieger dot test plot error ratio in the 0.4 group was significantly higher than that in the 0.2 group until 15 minutes post infusion. Sedation appears to be safe at the infusion doses of DEX studied. However, increasing maintenance infusion doses of DEX from 0.2 µg/kg/hr to 0.4 µg/kg/hr delays some recovery parameters.     

Helices F-G are important for the substrate specificities of CYP3A7.

CYP3A7 is a member of the human CYP3A family and a major form of P450 expressed in human fetal livers. Although CYP3A7 shares nearly 90% base sequence with CYP3A4, CYP3A7 shows striking functional differences in the catalytic preference for several substrates, such as dehydroepiandrosterone (DHEA) or dehydroepiandrosterone 3-sulfate (DHEA-3S). First, to clarify the reason for the differences between CYP3A7 and CYP3A4, a homology model of CYP3A7 was constructed using the CYP3A4 crystal structure. Because these two structures were similar, four kinds of chimeric enzymes were constructed to determine which sequences are important for exhibiting the characteristics of CYP3A7. The results of kinetic analysis of DHEA and DHEA-3S 16alpha-hydroxylations by CYP3A7, CYP3A4, and CYP3A chimeras suggested that the amino acid residues from Leu(210) to Glu(279) were important to express the specificity for substrates as CYP3A7. This region was on the F and G helices of the modeled CYP3A7. Furthermore, to assess which amino acid in this sequence is important for the substrate specificity of CYP3A7, a one-point mutation of CYP3A7 to CYP3A4 was made by site-directed mutagenesis. The mutants of K224T and K244E had lost DHEA and DHEA-3S 16alpha-hydroxylation activities. The mutants also greatly decreased the metabolism of testosterone, erythromycin, nevirapine, and triazolam relative to those activities of CYP3A7 wild-type enzyme. From these results, it is expected that CYP3A7 can recognize specific substrates using the lysines in F-G loops.     

Genetic polymorphism of aldehyde oxidase in Donryu rats.

One of major metabolic pathways of [(+/-)-4-(4-cyanoanilino)-5,6-dihydro-7-hydroxy-7H-cyclopenta[d]-pyrimidine] (RS-8359), a selective and reversible monoamine oxidase type A inhibitor, is the aldehyde oxidase-catalyzed 2-hydroxylation at the pyrimidine ring. Donryu rats showed a dimorphic pattern for the 2-oxidation activity with about 20- to 40-fold variations in the Vmax/Km values between a low and a high activity group. The rats were classified as extensive metabolizers (EM) and poor metabolizers (PM) of RS-8359, of which ratios were approximately 1:1. One rat among the EM rats of each sex showed extremely high activity, and they were referred to as ultrarapid metabolizers. There was no significant difference in the expression levels of mRNA of aldehyde oxidase between the EM and PM rats. Analysis of nucleotide sequences showed four substitutions, of which the substitutions at 377G>A and 2604C>T caused 110Gly-Ser and 852Ala-Val amino acid changes, respectively. Amino acid residue 110 is located very near the second Fe-S center of aldehyde oxidase. Its change from nonchiral Gly to chiral Ser may result in a conformational change of aldehyde oxidase protein with the shift of isoelectric point value from 5.0 in the EM rats to 6.2 in the PM rats. The 110Gly-Ser amino acid substitution (377G>A) may be primarily responsible for the variations of aldehyde oxidase activity observed in Donryu rats, in addition to the difference of expression levels of aldehyde oxidase protein. If a new drug candidate is primarily metabolized by aldehyde oxidase, attention should be given to using a rat strain with high aldehyde oxidase activity and small individual variation.     

Significant Increases in Serum CA125 and CA19-9 Following Torsion from an Adenofibroma of the Ovary: A Case Report

Significant increases in the serum levels of cancer antigen125 (CA 125) and carbohydrate antigen 19-9 (CA19-9) were observedover one month prior to the removal of an ovarian adenofibroma.The serum levels of CA125 and CA19-9 decreased rapidly aftersurgery. The surface of the tumor at surgery showed marked inflammation,probably induced by the necrosis produced by torsion. Pathologically,most of the tumor was necrotic, and histo immunochemical stainingof the viable cells was weak for CA125 but intense for CA19-9.Clinicopathological observations of the case suggested thatCA125 and CA19-9 might be stimulated in the cells by inflammationor that originally existing CAT25 and CA19-9 were released fromthe tumor cells following the cell necrosis.     

State of Adenomatous Polyposis Coli Gene and ras Oncogenes in Japanese Prostate Cancer

Genetic alterations of ras oncogenes (K-, H- and N- ras ) and adenomatous polyposis coli (APC) gene in tissues of prostate cancer from Japanese patients were examined using PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) analysis and direct sequencing. Tissues from 8 cases of untreated stage B prostate cancer surgically removed and from 10 cases of endocrine therapy-resistant metastatic disease obtained at autopsy were used in the present study. In four out of 18 cases (22%), ras point mutations were found, two in either codon 12 or 61 of K-ras and two in either 13 or 61 of H- ras . These point mutations were detected in one of the stage B cases (13%) and in three of the autopsy cases (30%). All these cases were poorly differentiated adenocarcinoma. In autopsy cases showing ras mutation in cancerous prostate, the same alteration was observed in metastatic tissues. No APC gene mutation was detected in any sample, although polymorphism was found in some cases. These results indicate that ras oncogene mutations are related to the progression of prostate cancer, whereas APC gene alteration is not involved in tumorigenesis and development of this cancer.     

Mutational Analysis of CDKN2 (CDK4I/MTS1) Gene in Tissues and Cell Lines of Human Prostate Cancer

To study mutation of the CDKN2 gene in prostate cancer, samples from 51 Japanese patients and four human prostate cancer cell lines were examined by single-strand conformation polymorphism analysis and direct sequencing. Only one out of 51 (2%) patients revealed a mutation, which was a 24 bp deletion from the 5'-untranslated region to codon 3, resulting in loss of the initiation site. One of the four cell lines revealed a missense mutation, a GAC→TAC (Asp→Tyr) at codon 84. These results indicate that mutation of the CDKN2 gene is rare in prostate cancer and thus does not contribute significantly to the pathogenesis of human prostate cancer. Prostate cancer cell lines may acquire more frequent abnormality of the CDKN2 gene than tumor tissues.     

Randomized study with mitomycin C + 5-fluorouracil + cytosine arabinoside (MFC) + 5-fluorouracil,MFC + tegafur and uracil (UFT), and MF + UFT in advanced gastric cancer: Interinstitutional differences in a multicenter study in Japan

In a phase III randomized trial of adjuvant chemotherapy for gastric cancer, interinstitutional differences were analyzed. A trial of three regimens: mitomycin C, 5-fluorouracil(5-FU) and CA (MFC) + continuous oral 5-FU (Group C); MFC + continuous oral UFT(tegafur and uracil) (Group B); and MF + UFT (Group C) after operation was conducted in 466 patients with gastric cancer (stage II and III) at four hospitals in Japan (CIH, CAD, ACC and NCC). Patients were stratified by the institution, stage, and tumor size (8 cm ><). The 5-year survival rates were in the order of Group A (79.0%) > B (70.0%) > C (61.0%) (P = 0.1228) in total, A (95.0%) > B (80.0%) > C (58.0%) (P < 0.05) at CAD (82 patients), A > C> B at CIH (215), C> A > B at ACC (95), and B > A > C at NCC (78). The survival rate of patients with S2(serosal exposure), 8 cm < and NO-1 cancer was higher at CIH than at the other institutions. The interinstitutional differences in patient characteristics and surgical technique were more powerful than the differences among the three groups. © 1995 Wiley-Liss, Inc.