Pseudomembranous colitis caused by topical clindamycin phosphate

Pseudomembranous colitis was observed on two occasions in the same patient and was associated with the topical administration of clindamycin phosphate. Assay for Clostridium difficile toxin was positive, and the patient was ultimately cured by oral vancomycin hydrochloride and the withdrawal of clindamycin therapy.     

Pharmacokinetic comparison of two valproic acid formulations--a plain and a controlled release enteric-coated tablets.

We investigated the single- and multiple dose pharmacokinetics of a new controlled-release formulation (Orfil retard enteric coated tablet) of valproic acid in comparison with those of the plain tablet as a reference. Twelve healthy volunteers were given each formulation of 300 mg in the single-dose study. In the steady-state multiple-dose study, twelve epileptic patients received 1200 mg/day of the reference drug (300 mg 9 AM, 300 mg 3 PM, 600 mg 9 PM) and the test formulation (600 mg 9 AM, 600 mg 9 PM) with at least one week interval in cross-over manner. The AUC values of the test controlled release formulation were 91.7% (95% confidence interval: 78.4-100.4%) of the reference drug in the single-dose study and 98.2% (95% confidence interval: 86.2%-109.9%) in the steady-state study. The AUC''s of the two formulations were not significantly different by ANOVA test. The Cmax and Tmax values of the test formulation were significantly different from the values of the reference in single-(Tmax: 158.4%, Cmax: 52.5% of the reference) and multiple-dose study (Tmax: 153.5% of the reference). The MRT values of the test formulation were also significantly greater (129.4% of the reference) in the single-dose study. Regarding the controlled-release characteristics of the test formulation, fluctuation index and percentage fluctuation of the twice a day dosage regimen of the test formulation were comparable with those of the thrice a day dosage regimen of the conventional tablet. Area deviation was even smaller in the test regimen of the controlled release formulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between urinary profile of the endogenous steroids and postmenopausal women with stress urinary incontinence.

AIMS: The aims of this study were to investigate whether endogenous steroid hormones are (1) related to pathogenesis of stress urinary incontinence after menopause, (2) are related to severity of stress urinary incontinence, and (3) are related to prognostic parameters of stress urinary incontinence. METHODS: Twenty post-partum women with clinically diagnosed stress urinary incontinence and 20 age-matched postmenopausal women without stress urinary incontinence (control group) were evaluated. We compared urinary profile of the endogenous steroid hormones patients with stress urinary incontinence and controls, and between grade I and grade II of stress urinary incontinence. We also investigated the relationship between urinary profile of the endogenous steroid hormones and prognostic parameters of stress urinary incontinence (maximal urethral closure pressure, functional urethral length, Valsalva leak point pressure, cough leak point pressure, posterior urethrovesical angle, bladder neck descent, and stress urethral axis). The ages of the patients and those in the control group were 64.3 +/- 5.6 and 57.5 +/- 3.8 years old and the body mass indexes were 24.96 +/- 3.14 and 22.11 +/- 2.73 kg/m2 in patients and in normal subjects, respectively. Nine patients were grade I and 11 were grade II. Estrone and 17beta-estradiol only were detected in all subjects, regardless of control or patient group. It is noteworthy that there were no significant differences (P > 0.05) in the levels of estrone and 17beta-estradiol in the urine of postmenopausal normal subjects compared with in the urine of postmenopausal patients with urinary incontinence. E2/E1 ratio was not different between the two groups (P > 0.05). Among the objective steroids, DHEA, Delta4-dione, Delta5-diol, Te, DHT, 16alpha-DHT, 11-keto An, THDOC, and THB were not detected either in the urine of normal subjects and nor in the urine of the patients. After comparing androgen levels between normal subjects and patients, no significant differences (P>0.05) were detected, except for 5alpha-THB and 5alpha-THF. Neither 5alpha-THB or 5alpha-THF were detected in the patients' urine. Et/An (11beta-OH Et/11beta-OH An) concentration ratios were not significantly different between the two groups, either (P > 0.05). There were not significant differences of concentrations (micromol/g creatinine) of urinary steroids between grade I and grade II of stress urinary incontinence. Pregnanediol was significantly related to bladder neck descent in supine and sitting positions (R = 0.79, P = 0.01, and R = 0.73, P = 0.03, respectively), and pregnanetriol was significantly related to maximal urethral closure pressure and functional urethral length (R = 0.68, P = 0.04, and R = -0.79, P = 0.01, respectively). Androsterone was significantly related to bladder neck descent in supine and sitting positions (R = 0.68, P = 0.04, and R = 0.78, P = 0.01, respectively). 5-AT was significantly related to bladder neck descent in sitting position and stress urethral axis (R = 0.72, P = 0.03, and R = -0.71, P = 0.03). 11-keto Et was significantly related to bladder neck descent in supine and sitting positions and related to stress urethral axis (R = 0.82, P = 0.01, and R = 0.81, P = 0.01, R = -0.67, P = 0.04, respectively). THS was significantly related to bladder neck descent in supine and sitting positions and related to stress urethral axis (R = 0.76, P = 0.02, and R = 0.74, P = 0.02, R = -0.68, P = 0.04, respectively). THE was significantly related to bladder neck descent in sitting position (R = 0.67, P = 0.04).beta-Tetrahydrocortisol/alpha-tetrahydrocortisol (beta-THF/alpha-THF) and alpha-cortol were significantly related to maximal urethral closure pressure and functional urethral length (R = 0.74, P = 0.02, and R = -0.92, P = 0.01; R = 0.71, P = 0.36, and R = -0.87, P = 0.000, respectively). 17beta-estradiol (E2) was significantly related to bladder neck descent in supine position (R = -0.62, P = 0.04) and 17beta-estradiol/estrone (E2/E1) was significantly related to cough leak point pressure (R = 0.79, P = 0.01). In conclusion, the urinary concentrations of endogenous steroid metabolites in postmenopausal patients with stress urinary incontinence were not significantly different from normal patients and were not significantly different between grade I and grade II patients with stress urinary incontinence. Some endogenous steroid metabolites were positively or negatively significantly related to prognostic parameters of stress urinary incontinence.     

Bivalirudin-associated intracoronary thrombosis during gamma-brachytherapy and its experimental validation in acute swine model.

Bivalirudin is indicated for use as an anticoagulant in patients with unstable angina undergoing percutaneous transluminal coronary angioplasty. Cases of intracoronary thrombosis have been reported with beta-radiation when bivalirudin is used as an anticoagulant. We report two cases of intracoronary thrombosis with gamma-radiation when bivalirudin is used.     

Claudin-7 is highly expressed in chromophobe renal cell carcinoma and renal oncocytoma

Claudin-7 has recently been suggested to be a distal nephron marker. We tested the possibility that expression of claudin-7 could be used as a marker of renal tumors originating from the distal nephron. We examined the immunohistochemical expression of claudin-7 and parvalbumin in 239 renal tumors, including 179 clear cell renal cell carcinoma (RCC)s, 29 papillary RCCs, 20 chromophobe RCCs, and 11 renal oncocytomas. In addition, the methylation specific-PCR (MSP) of claudin-7 was performed. Claudin-7 and parvalbumin immunostains were positive in 3.4%, 7.8% of clear cell RCCs, 34.5%, 31.0% of papillary RCCs, 95.0%, 80.0% of chromophobe RCCs, and 72.7%, 81.8% of renal oncocytomas, respectively. The sensitivity and specificity of claudin-7 in diagnosing chromophobe RCC among subtypes of RCC were 95.0% and 92.3%. Those of parvalbumin were 80.0% and 88.9%. The expression pattern of claudin-7 was mostly diffuse in chromophobe RCC and was either focal or diffuse in oncocytoma. All of the cases examined in the MSP revealed the presence of unmethylated promoter of claudin-7 without regard to claudin-7 immunoreactivity. Hypermethylation of the promoter might not be the underlying mechanism for loss of its expression in RCC. Claudin-7 can be used as a useful diagnostic marker in diagnosing chromophobe RCC and oncocytoma.     

Easy diagnosis of asthma: computer-assisted, symptom-based diagnosis

Diagnosis of asthma is often challenging in primary-care physicians due to lack of tools measuring airway obstruction and variability. Symptom-based diagnosis of asthma utilizing objective diagnostic parameters and appropriate software would be useful in clinical practice. A total of 302 adult patients with respiratory symptoms responded to a questionnaire regarding asthma symptoms and provoking factors. Questions were asked and recorded by physicians into a computer program. A definite diagnosis of asthma was made based on a positive response to methacholine bronchial provocation or bronchodilator response (BDR) testing. Multivariate logistic regression analysis was used to evaluate the significance of questionnaire responses in terms of discriminating asthmatics. Asthmatic patients showed higher total symptom scores than non-asthmatics (mean 5.93 vs. 4.93; p<0.01). Multivariate logistic regression analysis identified that response to questions concerning the following significantly discriminated asthmatics; wheezing with dyspnea, which is aggravated at night, and by exercise, cold air, and upper respiratory infection. Moreover, the presence of these symptoms was found to agree significantly with definite diagnosis of asthma (by kappa statistics). Receiver-operating characteristic curve analysis revealed that the diagnostic accuracy of symptom-based diagnosis was high with an area under the curve of 0.647 +/- 0.033. Using a computer-assisted symptom-based diagnosis program, it is possible to increase the accuracy of diagnosing asthma in general practice, when the facilities required to evaluate airway hyperresponsiveness or BDR are unavailable.     

Validation of intimate correlation between visceral fat and hepatic steatosis: Quantitative measurement techniques using CT for area of fat and MR for hepatic steatosis

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Nodular regenerative hyperplasia of the liver in Budd–Chiari syndrome: CT and MR features

We report the imaging findings of spiral computed tomography (CT), magnetic resonance (MR) imaging, and MR angiography in a patient with nodular regenerative hyperplasia of the liver associated with Budd–Chiari syndrome. Spiral CT showed multiple enhancing nodules during the hepatic arterial and portal venous phases. MR images showed multiple hyperintense nodules on T1-weighted images and hypointense or isointense nodules on T2-weighted images. MR angiography showed thrombotic occlusion of three hepatic veins, suggesting Budd–Chiari syndrome. Received: 25 June 1999/Revision accepted: 22 September 1999     

Bivalirudin versus heparin as an antithrombotic agent in patients who undergo percutaneous saphenous vein graft intervention with a distal protection device

Bivalirudin (Angiomax) is increasingly used as a substitute for heparin in a variety of percutaneous coronary interventions, and data on its usage in saphenous vein graft interventions are limited. This retrospective, observational study evaluated the efficacy and safety of bivalirudin compared with heparin as an antithrombotic regimen in patients who underwent saphenous vein graft intervention with distal protection devices. We found that bivalirudin use is clinically safe and feasible, with fewer vascular and ischemic complications compared with heparin.     

Role of Toll‐like receptor 9 signaling on activation of nasal polyp–derived fibroblasts and its association with nasal polypogenesis

Background

Nasal polyposis is characterized by persistent inflammation and remodeling in sinonasal mucosa. Toll‐like receptor 9 (TLR9) is a DNA receptor of the innate immune system that plays a pivotal role in fibrosis and inflammatory responses. The aim of this study is to explore the expression, activity, and potential pathogenic role of TLR9 signaling in tissue remodeling in nasal polyp–derived fibroblasts (NPDFs).

Methods

Fibrotic and inflammatory responses elicited by type A CpG oligonucleotides were examined in the NPDFs by a combination of real‐time quantitative polymerase chain reaction, Western blot analysis, enzyme‐linked immunosorbent assay, and immunofluorescence staining. For these experiments, the NPDFs were stimulated with different TLR9 agonists (CpG A and B) and blocked with inhibitors (MyD88 inhibitor and chloroquine).

Results

TLR9 expression was significantly higher in nasal polyposis (NP) tissues compared to control or chronic rhinosinusitis (CRS) mucosa. In the NPDFs, TLR9 showed intracellular localization and expression of TLR9 was increased after treatment with CpG A. CpG A increased production of α‐smooth muscle actin (α‐SMA), fibronectin, and matrix metalloproteinases (MMPs) (MMP1, MMP2, and MMP9) in the NPDFs, while MyD88 inhibitor and chloroquine, which are known to block the TLR9 signaling pathway, inhibited their production. CpG A also produced type I interferons (IFN‐α and IFN‐β), which were inhibited by MyD88 inhibitor.

Conclusion

Our data indicates that CpG A–induced fibroblast activation and cytokine production were mediated via TLR9 stimulation in NPDFs. Disrupting this process with an inhibitor targeting TLR9 or its downstream signaling pathways could represent a novel approach to CRS with NP (CRSwNP) therapy.