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1.
Int J Clin Pract ; 62(11): 1664-74, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18811599

ABSTRACT

INTRODUCTION AND OBJECTIVE: Patient perception of overactive bladder (OAB) treatment outcomes can be a useful indicator of benefit and may help drive persistence on treatment, which is known to be poor in OAB. It remains unclear whether OAB patients dissatisfied with one antimuscarinic can achieve satisfaction with another and supporting data are limited. This study investigated patient-reported outcomes and clinical parameters during darifenacin treatment in OAB patients who expressed dissatisfaction with prior extended-release (ER) oxybutynin or tolterodine therapy (administered for >or= 1 week within the past year). METHODS: This open-label study was conducted in darifenacin-naïve OAB patients. Patients received 7.5 mg darifenacin once daily with the possibility of up-titrating to 15 mg after 2 weeks, for up to 12 weeks. Efficacy parameters included the Patient's Perception of Bladder Condition (PPBC), patient satisfaction with treatment, micturition frequency and number of urgency and urge urinary incontinence (UUI) episodes. Adverse events (AEs) were also recorded. RESULTS: In total, 497 patients were treated (84.1% women). Darifenacin treatment resulted in statistically significant improvements in PPBC scores, micturition frequency, urgency and UUI episodes from baseline at 12 weeks. The improvements were similar for patients previously treated with oxybutynin ER or tolterodine ER. More than 85% of patients expressed satisfaction with darifenacin. As noted in other studies, the most common AEs were dry mouth and constipation, but these infrequently resulted in treatment discontinuation, which was low overall. CONCLUSIONS: In this study, PPBC score and OAB symptoms were significantly improved, and satisfaction was high during treatment with darifenacin (7.5/15 mg) in patients who were dissatisfied with the previous antimuscarinic treatment.


Subject(s)
Benzofurans/therapeutic use , Muscarinic Antagonists/therapeutic use , Patient Satisfaction , Pyrrolidines/therapeutic use , Urinary Bladder, Overactive/drug therapy , Adolescent , Adult , Aged , Female , Humans , Middle Aged , Treatment Outcome , Urinary Bladder, Overactive/physiopathology , Urinary Bladder, Overactive/psychology , Urination/physiology , Young Adult
2.
Minerva Ginecol ; 58(4): 265-82, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16957671

ABSTRACT

Urinary incontinence is a prevalent problem that affects women of all ages. We reviewed the pathophysiology, evaluation, and treatment of stress urinary incontinence. We performed a comprehensive review of the literature using MEDLINE and resources cited in those peer-reviewed manuscripts. The results are presented. Stress urinary incontinence is defined as leakage of urine that occurs with a sudden increase in intra-abdominal pressure, such as that seen with physical activity, without concomitant rise in detrusor (bladder-generated) pressure. It is a prevalent and costly problem that affects women worldwide. Proper and thorough evaluation is imperative in order to provide patients with appropriate treatment options and accurate counseling regarding the risks, benefits, and alternatives to the available therapies. Numerous new techniques have been developed in the treatment of stress incontinence, and the approaches continue to evolve. With the increasing number of patients seeking treatment for stress incontinence, it is essential to stay current with the latest concepts in the mechanism of stress incontinence and the techniques available for its treatment. An overview of the latest literature and principles is presented.


Subject(s)
Urinary Incontinence, Stress , Female , Humans , Prostheses and Implants , Urinary Incontinence, Stress/diagnosis , Urinary Incontinence, Stress/therapy , Urologic Surgical Procedures/methods
3.
Urology ; 66(4): 741-5, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16230128

ABSTRACT

OBJECTIVES: To report a premarket multicenter trial to test the feasibility of a transvaginal silicone-coated polyester synthetic mesh sling in women with anatomic incontinence. METHODS: Fifty-one patients in four centers underwent transvaginal placement of a silicone-coated polyester synthetic mesh sling (American Medical Systems) during an 8-month period. Of the 51 patients, 31 were part of a prospective institutional review board-approved feasibility trial in three centers funded by American Medical Systems (group 1) and 20 underwent implantation by a single surgeon and their data were retrospectively reviewed (group 2). The studies were done concomitantly, and all slings were fixed transvaginally with bone anchors. All patients in group 1 were followed up at 4 weeks, 6 months, and 1 year (as applicable) with repeat questionnaires, physical examinations, and pad tests. RESULTS: In group 1, 20 patients completed 6 months of follow-up. Ten patients (32%) required a second surgical procedure at an average of 183 days (range 68 to 343) postoperatively. Eight patients (26%) had vaginal extrusion of the mesh, one (3%) required sling lysis, and one (3%) required sling removal because of infection. In group 2, 8 patients (40%) underwent sling removal for vaginal extrusion at a mean of 160 days (range 83 to 214). CONCLUSIONS: Transvaginally placed silicone-coated mesh slings used for the treatment of urinary incontinence demonstrated an unacceptably high vaginal extrusion rate in this study. Once identified, this study was immediately terminated, and this product was not marketed for this application in the United States.


Subject(s)
Polyesters , Prostheses and Implants/adverse effects , Surgical Mesh/adverse effects , Urinary Incontinence/surgery , Adult , Aged , Aged, 80 and over , Feasibility Studies , Female , Humans , Middle Aged , Prospective Studies , Retrospective Studies , Urologic Surgical Procedures/methods
4.
Ann Nucl Med ; 15(3): 237-45, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11545194

ABSTRACT

In order to investigate the feasibility of the assessment of renal function with 99mTc-MDP, we compared renographical images, renogram patterns and the glomerular filtration rate (GFR) obtained by means of a modified Gates' method and 200 MBq of 99mTc-MDP with those obtained by means of 99mTc-DTPA. Because 19 of 20 patients had malignant tumors in the genitourinary tract, there was no difference between the two tracers in identifying a parenchymal defect corresponding to renal cancer. Of eight patients with hydronephrosis, four had a defect or decreased uptake with a dilated pelvis, whereas the other four had marked radioisotope retention in the renal pelvis or the whole kidney on serial images. There was also no difference between the two tracers in identifying hydronephrosis. Of 38 paired renograms 35 showed the same renogram patterns with both tracers. Of three patients with different renogram patterns, two had hydronephrosis. In 20 patients including three patients with bone metastasis, total GFR and split GFR obtained with both tracers correlated with a correlation coefficient of r = 0.920 (p < 0.001) and r = 0.944 (p < 0.001), respectively. Excluding bone metastasis from the analysis, a linear-regression analysis showed excellent agreement between the two measurements with a correlation coefficient of r = 0.960 (p < 0.001) and r = 0.963 (p < 0.001), respectively. The linear regression equations were Y = 1.009X - 0.111 and Y = 1.034X - 0.714, respectively. In conclusion, 99mTc-MDP can be used as a supplement to evaluate renal function incidental to the survey of bone metastases in patients with malignant tumor.


Subject(s)
Bone Neoplasms/diagnostic imaging , Bone Neoplasms/secondary , Bone and Bones/diagnostic imaging , Kidney/diagnostic imaging , Technetium Tc 99m Medronate , Urogenital Neoplasms/diagnostic imaging , Aged , Aged, 80 and over , Blood Urea Nitrogen , Creatinine/blood , Female , Glomerular Filtration Rate , Humans , Hydronephrosis/diagnostic imaging , Kidney Neoplasms/diagnostic imaging , Male , Middle Aged , Prostatic Neoplasms/diagnostic imaging , Radioisotope Renography , Radiopharmaceuticals/pharmacokinetics , Technetium Tc 99m Medronate/pharmacokinetics , Tissue Distribution , Urinary Bladder Neoplasms/diagnostic imaging , Urogenital Neoplasms/pathology
5.
Curr Opin Urol ; 11(4): 405-10, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11429502

ABSTRACT

The pubovaginal sling, reintroduced in the late 1970s by Maguire and Blaivas, has become the gold standard for managing anatomic incontinence. Newer technology, materials, surgical techniques and even new theories on the mechanism of action are evolving to further reduce the morbidity of these procedures and improve patient satisfaction. In the following review, we will highlight some of the exciting advances we have witnessed over the last year and try to put them into perspective for the reader.


Subject(s)
Urinary Incontinence/surgery , Fascia/transplantation , Female , Humans , Pubic Bone , Surgical Mesh , Urologic Surgical Procedures/adverse effects , Urologic Surgical Procedures/methods , Vagina
6.
Gan To Kagaku Ryoho ; 28(4): 483-91, 2001 Apr.
Article in Japanese | MEDLINE | ID: mdl-11329782

ABSTRACT

An early phase II study (dose-finding study) of amrubicin hydrochloride for superficial bladder cancer was conducted. Amrubicin was dissolved in 30 ml of physiological saline and injected intravesically for 6 consecutive days. The drug solution was retained for 2 hours. Patients were randomly assigned to four groups, which were administered amrubicin at doses of 30, 60, 90, and 120 mg/day, respectively. Of 65 patients registered in this study, 63 were eligible and assessable for toxicities, and 55 assessable for efficacy. The response rate at each dose level was 50.0% (7PRs/14 patients) at 30 mg/day, 53.3% (8 PRs/15) at 60 mg/day, 61.5% (2 CRs + 6 PRs/13) at 90 mg/day, and 69.2% (2 CRs + 7 PRs/13) at 120 mg/day, respectively. These data suggests that the efficacy was related to the doses of amrubicin. The major toxicities were cystic irritabilities, such as micturition pain, pollakisuria and hematuria. These toxicities were related to the doses of amrubicin. Their incidence and the severity were not high compared with those reported about other anthracyclines such as doxorubicin and epirubicin. The optimal dose of amrubicin was estimated to be 90 to 120 mg/day in the intravesical treatment for superficial bladder cancer once a day for 6 consecutive days.


Subject(s)
Anthracyclines/administration & dosage , Antineoplastic Agents/administration & dosage , Urinary Bladder Neoplasms/drug therapy , Administration, Intravesical , Aged , Anthracyclines/adverse effects , Antineoplastic Agents/adverse effects , Drug Administration Schedule , Female , Hematuria/chemically induced , Humans , Male , Middle Aged , Pain/etiology , Urinary Bladder Neoplasms/physiopathology , Urination
8.
Curr Urol Rep ; 2(5): 392-8, 2001 Oct.
Article in English | MEDLINE | ID: mdl-12084247

ABSTRACT

Repair of cystoceles requires a complete understanding of the pelvic anatomy. While smaller defects are relatively straightforward, greater degrees of prolapse can be among the most challenging surgeries in pelvic floor reconstruction. This article reviews current transvaginal techniques used for repair of large cystoceles.


Subject(s)
Urinary Bladder Diseases/pathology , Urinary Bladder Diseases/surgery , Vagina/surgery , Female , Humans , Severity of Illness Index
9.
J Otolaryngol ; 30(3): 157-61, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11771045

ABSTRACT

OBJECTIVE: We examined cathepsin L activity, expression of cystatin A, and copper- and zinc-containing superoxide dismutase in human chronic otitis media. The relationships of our findings to clinical findings (e.g., grade of bone destruction) were also studied. DESIGN: Retrospective basic and clinical study. SETTING: Department of Otolaryngology and First Department of Biochemistry, Kinki University School of Medicine, Osaka, Japan. METHOD: The human middle ear tissues evaluated in this study were surgically obtained from seven patients with cholesteatoma epithelium, three patients with granulation tissues in cholesteatoma, three patients with granulation tissues in noncholesteatoma, and three patients with intact mucous membrane of the middle ear. MAIN OUTCOME MEASURES: Cathepsin L activities in cholesteatoma epithelium, granulation tissues in cholesteatoma, or granulation tissues in noncholesteatoma were measured using Barrett's method. Cystatin A expressions were observed by Western blot analysis. Copper- and zinc-containing superoxide dismutase in cholesteatoma was examined immunohistochemically. RESULTS: Mean cathepsin L activity was higher in diseased tissues than in intact mucous membranes of the middle ear. Granulation tissues with high cathepsin L activity resulted in extensive bone destruction in both cholesteatomas and noncholesteatomas of the middle ear. All cases with intact mucous membrane of the middle ear exhibited no expression of cystatin A. Seven of 10 cases with diseased tissues expressed cystatin A in cholesteatoma epithelium, granulation tissues in cholesteatoma, or granulation tissues in noncholesteatoma. No relationships were found between cystatin A expression and grade of cathepsin L activity. Copper- and zinc-containing superoxide dismutase was more strongly positive in cholesteatoma epithelium regions than in granulation tissues. CONCLUSION: These results suggest that copper- and zinc-containing superoxide dismutase in cholesteatoma epithelium prevents complications by suppressing cathepsin L activity.


Subject(s)
Cathepsins/metabolism , Cholesteatoma, Middle Ear/metabolism , Cholesteatoma, Middle Ear/pathology , Ear, Middle/metabolism , Ear, Middle/pathology , Otitis Media/metabolism , Otitis Media/pathology , Superoxide Dismutase/physiology , Cathepsin L , Cystatins/metabolism , Cysteine Endopeptidases , Ear Ossicles/pathology , Epithelium/metabolism , Epithelium/pathology , Granulation Tissue/metabolism , Granulation Tissue/pathology , Humans , Retrospective Studies , Superoxide Dismutase/metabolism
10.
Anticancer Res ; 21(5): 3285-93, 2001.
Article in English | MEDLINE | ID: mdl-11848485

ABSTRACT

Interleukin-18 (IL-18) is a powerful inducer of interferon-gamma (IFN-gamma), a key immunoregulatory cytokine. Cellular immune responsiveness, as measured by IL-18-induced IFN-gamma production from peripheral blood mononuclear cells (PBMCs) in ELISA assay, was evaluated in 10 patients with advanced cancer and in 10 normal controls. Supernatant levels of IFN-gamma were detected at 2 hours after PBMCs culture and markedly increased thereafter in healthy volunteers. In contrast, IFN-gamma production in cancer patients was not detected during the culture period (0-72 hours). We also measured IL-18-stimulated IL-12 production in healthy volunteers and null response was observed in cancer-bearing patients. Next, we studied mRNA expressions of IL-18 receptor (IL-18R) and IFN-gamma in PBMCs in cancer patients and healthy volunteers by RT-PCR assay. Both mRNA levels of IL-18R and IFN-gamma were significantly decreased in cancer-bearing patients compared with normal controls. These results suggested that IL-18 responsiveness for IFN-gamma production in cancer-bearing patients was impaired. Using flow cytometric analysis, we studied T-cell subsets, CD3- CD56+ (NK cell), CD3+ CD45RO+ (memory T-cell), CD3+ CD95+ (Fas+ T-cell), CD3+ CD4+ (helper T-cell), CD3+ CD8+ (cytotoxic T-cell: CTL) and CD3+ V alpha24+ (NKT-cell), in cancer patients and normal controls. The NK and cytotoxic T-cells significantly decreased and NKT-cells had decreased tendency in cancer patients compared with normal controls. In contrast, memory T cells, Fas+ T-cells and helper T-cells were all significantly increased in cancer patients compared with normal controls. These results suggested that the underlying mechanism of impaired IL-18 responsiveness in PBMCs from cancer-bearing patients was, at least in part, ascribed to a drastic decrease of NK cells and CTL which constitutively and highly express IL-18R and also attributed to null production of IL-12 which up-regulates IL-18R.


Subject(s)
Neoplasms/metabolism , Receptors, Interleukin/biosynthesis , Adult , Aged , Down-Regulation , Female , Flow Cytometry , Humans , Interferon-gamma/biosynthesis , Interferon-gamma/genetics , Interleukin-12/biosynthesis , Interleukin-18/pharmacokinetics , Interleukin-18/pharmacology , Interleukin-18 Receptor alpha Subunit , Killer Cells, Natural/cytology , Killer Cells, Natural/immunology , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Lymphocyte Subsets , Male , Middle Aged , Neoplasms/genetics , Neoplasms/immunology , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Receptors, Interleukin/genetics , Receptors, Interleukin/metabolism , Receptors, Interleukin-18 , T-Lymphocytes, Cytotoxic/cytology , T-Lymphocytes, Cytotoxic/immunology
11.
Urology ; 56(6 Suppl 1): 9-14, 2000 Dec 04.
Article in English | MEDLINE | ID: mdl-11114557

ABSTRACT

A new technique using cadaveric fascia lata for the simultaneous repair of a cystocele and placement of a pubovaginal sling by means of a transvaginal approach is described, and our early results are reported. We refer to this as the cadaveric prolapse repair with sling (CaPS). Fifty patients, ages 37 to 90 years, underwent a new technique for simultaneous cystocele repair and transvaginal pubovaginal sling using a single piece of cadaveric fascia. Maximum follow-up was 6 months (range 1 to 6). A 6 x 8 cm segment of cadaveric fascia lata is placed transvaginally to repair the defect through which the bladder herniates into the vagina and to provide sling support at the bladder neck/proximal urethra. The sling is anchored to the pubic bone with transvaginal bone anchors. The remainder of the fascia is then secured to the medial edge of the levator muscles/pubocervical fascia bilaterally and at the vaginal cuff or cervix with absorbable sutures to reduce the cystocele. Patients are being evaluated with preoperative and postoperative stress, emptying, anatomy, protection, instability (SEAPI) scores as well as with grading of the prolapse based on a 3-grade anatomic classification system. Presenting symptoms have included stress urinary incontinence (SUI) in 13 (26%), urge incontinence in 4 (8%), mixed incontinence in 6 (12%), and pelvic prolapse in 20 (40%). These symptoms are not mutually exclusive; some patients presented with a combination of symptoms. The mean SEAPI scores were 5.51 preoperatively and 0.63 postoperatively, representing a significant improvement (P <0.001). Of the 40 patients whose prolapse was quantified, 1 patient (2.5%) had a minimal cystocele, 16 (40.0%) had moderate cystoceles, and 23 (57.5%) had large cystoceles. After the CaPS, 36 (72%) were completely dry, 3 (6%) had persistent SUI, 1 (2%) had de novo urinary incontinence (UI), 3 (6%) had persistent UI, and 1 (2%) had mixed incontinence. No patient had permanent urinary retention. Transvaginal placement of cadaveric fascia for concomitant sling and cystocele repair provides material of excellent strength for the repair without relying on the inherently weak tissues in the patient with pelvic prolapse. Thus far, the early results with CaPS are extremely encouraging. Long-term follow-up is underway to evaluate the efficacy of this procedure.


Subject(s)
Fascia Lata/surgery , Urinary Bladder Diseases/surgery , Adult , Aged , Aged, 80 and over , Cadaver , Female , Follow-Up Studies , Humans , Length of Stay , Middle Aged , Reoperation , Retrospective Studies , Suture Techniques , Treatment Outcome , Urinary Bladder/surgery , Urinary Bladder Diseases/complications , Urinary Incontinence, Stress/etiology , Urinary Incontinence, Stress/surgery
12.
Acta Med Okayama ; 54(5): 201-9, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11061569

ABSTRACT

Tacrolimus (FK-506) and cyclosporin A (CsA) are calcineurin antagonists used widely as T-cell immunosuppressants; however, their relative efficacy on the production of interleukin-18 (IL-18) remains undefined. We have examined the effects of FK-506 and CsA on the cytokine generation of human peripheral blood mononuclear cells (PBMCs) in mixed lymphocyte reaction (MLR) with lipopolysaccharide (LPS). We studied the levels of interleukin-18 (IL-18), IL-12, IL-10, IL-6, IL-2 and interferon-gamma (IFN-gamma) in the supernatant in allo-MLR by ELISA assay. Supernatant levels of IFN-gamma, IL-2, IL-6, IL-10 and IL-12 were detected 12 h after MLR and markedly increased thereafter. In contrast, production of IL-18 was detected at 12 h, reached a near maximum level at 24 h and decreased at 72 h. These results suggested that IFN-gamma production depended on IL-18, IL-12 and IL-2 in the early phase of MLR and depended mainly on IL-12 and IL-2 in the late phase. Both calcineurin antagonists inhibit the generation of IL-18, which plays a large role in allogeneic cell interactions, in macrophages and they also promote an equivalent down-regulation of T helper 1 (Th1) and Th2 responses in a concentration-dependent manner. About 90% of IFN-gamma production induced by MLR was inhibited by an anti-IL-18 antibody, showing that IL-18 can trigger IFN-gamma production in MLR. These results suggest that dual signaling consisting of antigen-driven nuclear factor of activated T cells (NFAT) activation and LPS-mediated NF-kappaB activation is crucial for IL-18 production in macrophages, and that IL-18 can trigger IFN-gamma production in T-cells by MLR.


Subject(s)
Calcineurin Inhibitors , Cyclosporine/pharmacology , Immunosuppressive Agents/pharmacology , Interferon-gamma/biosynthesis , Interleukin-18/biosynthesis , Tacrolimus/pharmacology , Down-Regulation , Humans , Lymphocyte Culture Test, Mixed
13.
J Urol ; 164(6): 1879-90, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11061873

ABSTRACT

PURPOSE: Pelvic prolapse is a common problem affecting women of all ages. We reviewed the pathophysiology, presentation, evaluation and treatment of pelvic prolapse. MATERIALS AND METHODS: We comprehensively reviewed the literature using MEDLINE, resources cited in those peer reviewed articles and abstracts from recent international meetings. RESULTS: Pelvic prolapse involves the herniation of various portions of the vaginal wall. Symptoms vary according to the area of the vagina affected. Proper evaluation is imperative for providing proper treatment. Various surgical approaches to repair have been developed and techniques continue to evolve. CONCLUSIONS: With the increasing involvement of urologists in the treatment of pelvic prolapse it is essential for us to become familiar with the anatomy, and the evaluation and management options available. We provide an overview of the care of patients with pelvic prolapse.


Subject(s)
Rectocele , Urinary Bladder Diseases , Uterine Prolapse , Diagnosis, Differential , Female , Hernia/diagnosis , Herniorrhaphy , Humans , Rectocele/diagnosis , Rectocele/surgery , Urinary Bladder Diseases/diagnosis , Urinary Bladder Diseases/surgery , Uterine Prolapse/diagnosis , Uterine Prolapse/pathology , Uterine Prolapse/surgery , Uterus/pathology , Vagina/pathology
14.
J Int Med Res ; 28(3): 132-42, 2000.
Article in English | MEDLINE | ID: mdl-10983863

ABSTRACT

The expression of Fas, a cell surface receptor directly responsible for triggering cell death by apoptosis, and its ligand (FasL) was investigated on both human colonic intraepithelial T lymphocytes (IELs) and peripheral blood mononuclear lymphocytes (PBMLs). FACS analysis indicated that IELs have increased expression of Fas compared with PBMLs, together with the progress activation marker, CD45RO. A discrete fraction of freshly isolated IELs also constitutively expressed FasL, perhaps as a result of recent in vivo activation. Using monoclonal antibody APO2.7, which detects mitochondrial 7A6 antigen specifically expressed by cells undergoing apoptosis, we further investigated the apoptosis-inducing effect of anti-Fas monoclonal antibody (CH11) on both IELs and PBMLs. FACS analysis revealed that CH11 increased the percentage of apoptotic cells, in IELs but not in PBMLs. Culture with anti-FasL monoclonal antibody (4H9) significantly recovered cell viability in IELs, but not in PBMLs. These results indicate that IELs constitutively express both Fas and FasL and that Fas crosslinking generates signals resulting in apoptosis, outlining a potential mechanism involved in intestinal tolerance.


Subject(s)
Colon/metabolism , Membrane Glycoproteins/biosynthesis , T-Lymphocytes/metabolism , fas Receptor/biosynthesis , Adult , Aged , Antibodies, Monoclonal/immunology , Apoptosis , Cell Survival , Colon/pathology , Fas Ligand Protein , Humans , Immunophenotyping , Intestinal Mucosa , Leukocyte Common Antigens/biosynthesis , Middle Aged , T-Lymphocytes/cytology , T-Lymphocytes/immunology
15.
Xenobiotica ; 30(7): 707-15, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10963061

ABSTRACT

1. Deconjugation by sulphate transfer and intestinal absorption of troglitazone sulphate (M1), the major metabolite of a thiazolidinedione antidiabetic drug, troglitazone, were studied in the male F344 rat using 14C-troglitazone, 4C-M1 and 35S-M1. 2. Some part of M1, produced in the liver and excreted mostly in the bile, was deconjugated in the intestine to the parent compound, troglitazone, by arylsulphate sulphotransferase originated from intestinal flora. However, deconjugation of M1 was not catalyzed by arylsulphatases. Caecal injection of M1 led to the appearance of troglitazone and M1 in plasma. 3. Biliary excretion mostly as M1, and, following absorption, as M1 and troglitazone after deconjugation, were indicated as the basis for the enterohepatic circulation of troglitazone. 4. Enterohepatic circulation may prolong the pharmacological effects of troglitazone.


Subject(s)
Bile/metabolism , Chromans/pharmacokinetics , Hypoglycemic Agents/pharmacokinetics , Intestinal Absorption/physiology , Thiazoles/pharmacokinetics , Thiazolidinediones , Animals , Biotransformation , Cecum/metabolism , Chromans/urine , Chromatography, Thin Layer , Enterohepatic Circulation , Feces/chemistry , Hypoglycemic Agents/urine , In Vitro Techniques , Male , Rats , Rats, Inbred F344 , Sulfates/metabolism , Sulfates/urine , Thiazoles/urine , Troglitazone
16.
Anticancer Res ; 20(3B): 2223-7, 2000.
Article in English | MEDLINE | ID: mdl-10928182

ABSTRACT

A rare case of ruptured hepatocellular carcinoma (HCC) of the caudate lobe is reported. A 67-year-old man came to the hospital with complaints of abdominal pain and distension. Computed tomography (CT) showed haemoperitoneum and a mass in the caudate lobe. Angiography demonstrated a tumor stain. However, extravasation of the contrast medium was not clear. Although transcatheter arterial embolization (TAE) was performed, bleeding from the tumor could not be controlled. The caudate lobe, including the tumor, was resected. The patient died of multiple organ failure despite intensive care. This case suggests that TAE is not always effective and may not be safely or easily performed when treating ruptured HCC in the caudate lobe. This is attributed to the multiple feeding arteries of the tumor, derived from the proximal portion of the right and left hepatic arteries. If bleeding from the ruptured HCC in the caudate lobe is not controlled, immediate resection of the tumor is recommended.


Subject(s)
Carcinoma, Hepatocellular/complications , Liver Diseases/etiology , Liver Neoplasms/complications , Aged , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Embolization, Therapeutic , Fatal Outcome , Hemoperitoneum/etiology , Hepatectomy , Hepatic Artery , Humans , Liver/blood supply , Liver/pathology , Liver Diseases/diagnostic imaging , Liver Diseases/therapy , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Male , Multiple Organ Failure/etiology , Postoperative Complications , Rupture, Spontaneous , Tomography, X-Ray Computed
17.
J Immunol ; 164(12): 6640-6, 2000 Jun 15.
Article in English | MEDLINE | ID: mdl-10843724

ABSTRACT

Histamine (10-7 to 10-4 M) concentration-dependently stimulated the production of IL-18 and IFN-gamma and inhibited the production of IL-2 and IL-10 in human PBMCs. Histamine in the same concentration range did not induce the production of IL-12 at all. The stimulatory or inhibitory effects of histamine on cytokine production were all antagonized by H2 receptor antagonists ranitidine and famotidine in a concentration-dependent manner, but not by H1 and H3 receptor antagonists. Selective H2 receptor agonists, 4-methylhistamine and dimaprit, mimicked the effects of histamine on five kinds of cytokine production. The EC50 values of histamine, 4-methylhistamine, and dimaprit for the production of IL-18 were 1.5, 1.0, and 3.8 microM, respectively. These findings indicated that histamine caused cytokine responses through the stimulation of H2 receptors. All effects of histamine on cytokine responses were also abolished by the presence of either anti-IL-18 Ab or IL-1beta-converting enzyme/caspase-1 inhibitor, indicating that the histamine action is dependent on mature IL-18 secretion and that IL-18 production is located upstream of the cytokine cascade activated by histamine. The addition of recombinant human IL-18 to the culture concentration-dependently stimulated IL-12 and IFN-gamma production and inhibited the IL-2 and IL-10 production. IFN-gamma production induced by IL-18 was inhibited by anti-IL-12 Ab, showing the marked contrast of the effect of histamine. Thus histamine is a very important modulator of Th1 cytokine production in PBMCs and is quite unique in triggering IL-18-initiating cytokine cascade without inducing IL-12 production.


Subject(s)
Histamine/pharmacology , Interferon-gamma/biosynthesis , Interferon-gamma/blood , Interleukin-18/biosynthesis , Interleukin-18/blood , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/immunology , Adjuvants, Immunologic/pharmacology , Antibodies, Monoclonal/pharmacology , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Caspase Inhibitors , Cells, Cultured , Culture Media, Conditioned/metabolism , Cytokines/biosynthesis , Enzyme Inhibitors/pharmacology , Histamine/metabolism , Histamine Agonists/pharmacology , Histamine Antagonists/pharmacology , Humans , Interleukin-10/biosynthesis , Interleukin-10/blood , Interleukin-12/biosynthesis , Interleukin-12/blood , Interleukin-12/immunology , Interleukin-18/immunology , Interleukin-18/physiology , Interleukin-2/biosynthesis , Interleukin-2/blood , Leukocytes, Mononuclear/metabolism , Methylhistamines/metabolism , Monocytes/drug effects , Monocytes/immunology , Monocytes/metabolism , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
18.
J Pediatr Surg ; 35(3): 446-9, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10726686

ABSTRACT

BACKGROUND/PURPOSE: Interleukin-18 (IL-18)/interferon-gamma-inducing factor (IGIF) is a novel proinflammatory cytokine that can induce interferon gamma (IFN-gamma). In addition, IL-18 enhances intracellular adhesion molecule-1 (ICAM-1) expression as well as Fas ligand (FasL) expression, and induces apoptosis in hepatic injury. The aim of this study was to clarify the potential role of IL-18 in the pathogenesis of the progressive inflammation and fibrosis in biliary atresia (BA). METHODS: Six children with BA before hepatic portoenterostomy (HPE), 13 with BA including 7 without jaundice and 6 with persistent jaundice after HPE, and 16 healthy controls were examined. Blood samples were obtained preoperatively from 6 patients, after HPE from 13, and after liver transplantation from 4. The IL-18 level was determined by an enzyme-linked immunosorbent assay (ELISA). Immunohistochemically, liver specimens from BA patients were studied using a monoclonal antibody to macrophage-associated antigen (CD68). RESULTS: IL-18 levels were elevated in the patients before HPE compared with those of the controls (349+/-54 pg/mL v. 138+/-13 pg/mL, P<.0001). After HPE, extremely high concentrations of IL-18 were observed in patients with persistent jaundice (532+/-95 pg/mL, P<.0001), and the IL-18 levels were significantly high even in the patients without jaundice (249+/-29 pg/mL, P<0.005). The high IL-18 level lasted for a long time even in the patients without jaundice after HPE. In contrast, the IL-18 levels immediately decreased after liver transplantation. Immunohistochemically, the number of CD68-positive Kupffer cells was significantly higher, and the size was larger in the livers of the patients than in the controls. The proliferation of CD68-positive cells was much more conspicuous in the liver specimens obtained during liver transplantation than in those at the time of HPE. CONCLUSIONS: Our findings showed elevation of serum IL-18 levels and activation of Kupffer cells in BA. IL-18 released from activated Kupffer cells might play an important role in the pathophysiology of the progressive inflammation and fibrosis in BA. Furthermore, IL-18 level may be related to the prognosis in patients with BA.


Subject(s)
Biliary Atresia/etiology , Interleukin-18/blood , Kupffer Cells/physiology , Antigens, CD , Antigens, Differentiation, Myelomonocytic , Apoptosis , Biliary Atresia/blood , Biliary Atresia/immunology , Biliary Atresia/surgery , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Humans , Infant , Kupffer Cells/immunology , Liver/immunology , Liver/pathology , Liver Transplantation , Portoenterostomy, Hepatic , Prognosis
19.
J Pharm Pharmacol ; 52(12): 1563-8, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11197087

ABSTRACT

When baicalin was orally administered to conventional rats, it was detected in their plasma for 24 h after administration, but baicalein, the aglycone of baicalin, was not detected. However, when baicalin was given to germ-free rats, only a small amount of baicalin was detected in their plasma within 2 h after the administration, its AUC0-lim (the area under the concentration-time curve from 0 to last determination time) being 12.0% of that in conventional rats. Subsequently, a considerable amount (55.1 +/- 6.2%) of baicalin was recovered from the gastrointestinal tract even 4 h after administration. When baicalein was orally administered to conventional rats, however, baicalin appeared rapidly in their plasma at an AUC0-lim value similar to that obtained after oral administration of baicalin, despite the absence of baicalein in plasma. When intestinal absorption was evaluated by the rat jejunal loop method, baicalein was absorbed readily, but only traces of baicalin were absorbed. Moreover, in conventional rats a small amount (13.4 +/- 3.1%) of baicalin and an appreciable amount (21.9 +/- 3.4%) of baicalein were recovered from the gastrointestinal tract even 4 h after oral administration of baicalin, but only a small amount (3.93 +/- 1.43%) of baicalein was detected in the intestinal tract 1 h after administration of baicalein. Baicalin was transformed to baicalein readily by the rat gastric and caecal contents. When baicalin was administered orally to conventional rats, an appreciable amount of baicalein was recovered in their gastrointestinal tracts. Moreover, baicalein was efficiently conjugated to baicalin in rat intestinal and hepatic microsomes. These results indicate that baicalin itself is poorly absorbed from the rat gut, but is hydrolysed to baicalein by intestinal bacteria and then restored to its original form from the absorbed baicalein in the body.


Subject(s)
Drugs, Chinese Herbal/pharmacokinetics , Flavanones , Flavonoids/metabolism , Flavonoids/pharmacokinetics , Administration, Oral , Animals , Area Under Curve , Bacteria/metabolism , Biotransformation , Drugs, Chinese Herbal/metabolism , Flavonoids/blood , Glucuronides/pharmacokinetics , Glucuronosyltransferase/metabolism , Intestinal Absorption , Intestinal Mucosa/enzymology , Intestinal Mucosa/metabolism , Intestines/microbiology , Male , Metabolic Clearance Rate , Microsomes, Liver/enzymology , Nitrophenols/metabolism , Plants, Medicinal/chemistry , Rats , Rats, Wistar , Specific Pathogen-Free Organisms , Time Factors
20.
Urology ; 55(3): 436, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10754171

ABSTRACT

Female urinary retention is extremely rare. Two cases of female urethral carcinoma that presented as urinary retention are reviewed and discussed.


Subject(s)
Adenocarcinoma/diagnosis , Carcinoma, Transitional Cell/diagnosis , Urethral Neoplasms/diagnosis , Urinary Retention/etiology , Adenocarcinoma/complications , Aged , Biopsy , Carcinoma, Transitional Cell/complications , Female , Humans , Magnetic Resonance Imaging , Middle Aged , Tomography, X-Ray Computed , Urethral Neoplasms/complications
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