The Effect of Biliary Pressure on Antibiotic Excretion into Bile

Abstract: Biliary obstruction has been recognized to inhibit excretion of antibiotics into bile. In the present study, using cefpirome sulfate (CPR), we sought to determine the effect of biliary pressure on antibiotic transfer into bile in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). Thirty-six patients with a variety of biliopancreatic diseases (free of renal disease or hypoproteinemia) received a single intravenous dose of CPR (1 g) prior to ERCP. Under fluoroscopy a diagnostic catheter with a metal ball tip was advanced into the middle portion of the extrahepatic bile duct or, in cases of common bile duct obstruction, above the obstruction. Biliary pressure was measured via the same catheter using duodenal pressure as a reference. Subsequently, bile was aspirated, and blood was withdrawn simultaneously. The mean interval between CPR administration and the bile and blood samplings was 67±12 minutes. The bile CPR concentration and the bile/serum ratio of CPR concentrations showed a significant inverse correlation with biliary pressure, but the serum CPR concentration did not. The bile CPR concentration and the bile/serum ratio of CPR concentrations differed significantly between the group with normal biliary pressures, below 10 mmHg, and that with biliary pressures exceeding 10 mmHg. The serum CPR concentrations of the two groups were similar. These results suggest that biliary pressure plays an important role in determining antibiotic transfer into bile.     

Synchronous granular cell tumor of the bladder, endometrial carcinoma and endometrial stromal sarcoma

We describe a very rare case of synchronous granular cell tumor of the bladder, endometrial carcinoma and endometrial stromal sarcoma. A 55‐year‐old woman with a 4‐month history of genital bleeding was cytologically diagnosed with endometrial carcinoma. Imaging studies suggested concomitant bladder tumor with the possibility of direct invasion from endometrial carcinoma. Total abdominal hysterectomy with bilateral salpingo‐oophorectomy and transurethral resection of bladder tumor was performed. The bladder tumor comprised polygonal cells with abundant eosinophilic, finely granular cytoplasm, separated by collagenous tissue. Neither nuclear pleomorphism nor tumor necrosis was found. Immunohistochemical expression of neural markers of neuron‐specific enolase and S‐100 allowed the diagnosis of granular cell tumor (GCT) of the bladder. Microscopic examination of endometrium revealed endometrioid adenocarcinoma with squamous differentiation (EAC). Ill‐defined nodular lesion comprising endometrial stromal sarcoma (ESS) was accidentally found in myometrium. Postoperatively, the patient underwent radiotherapy. This is the first well‐documented case of synchronous triple tumors comprising GCT of the bladder, uterine EAC and ESS.     

The female partner''s satisfaction with sildenafil citrate treatment of erectile dysfunction

BACKGROUND: Data on female partners' satisfaction are scarce, although there have been many articles on patient satisfaction after sildenafil citrate treatment. The aim of this study was to evaluate the satisfaction of female partners of patients receiving sildenafil citrate for their erectile dysfunction (ED) and to assess the female partners' sexual function. METHODS: Ninety-eight patients with ED were treated. Their female partners were asked to answer a questionnaire we have prepared to evaluate the efficacy of treatment, sexual satisfaction and changes in quality of life. It also included a question about female sexual function. From the results, the relationship between their female partner's satisfaction and efficacy of treatment, as well as female sexual function, were assessed. RESULTS: Thirty (31%) questionnaires were returned to us for analysis. Effectiveness of the treatment was acknowledged by 90% of the partners. An improvement in their partner's quality of life was noticed by 60% of the women. The majority (66.7%) of the female partners were satisfied with sildenafil citrate treatment and 20% were disappointed. Moreover, 20% of the female partners were concerned about adverse events. Regarding female sexual function, some form of sexual dysfunction affected 46.7% of the women. Furthermore, a significant number (P = 0.0230) of the female partners disappointed with the treatment had some kind of sexual dysfunction. CONCLUSIONS: The results indicated that female partners reported relatively high levels of treatment satisfaction. Female partners' sexual function and anxiety regarding adverse events should be evaluated when their satisfaction with sildenafil citrate treatment is poor despite an improvement of erectile function.     

A Structure-Relationship Study of the Uptake of Aliphatic Polyamine Compounds by Rat Intestinal Brush-border Membrane Vesicles

The effects of lipophilicity, ion-diffusion potential and membrane surface potential on the uptake of various aliphatic polyamine compounds by rat intestinal brush-border membrane vesicles (BBMV) have been investigated. A valinomycin-induced potassium-diffusion potential (inside-negative) stimulated the initial uptake of diamine compounds, and good correlation was observed between lipophilicity and the amount of diffusion-potential-dependent transport of the diamines. In contrast, because of their much lower lipophilicity, tri- and tetraamine compounds were not affected by the diffusion potential. Tetracaine, which can make the membrane surface potential more positive, inhibited the transport rate of 1,9-nonanediamine, spermidine and spermine by the BBMV. These data suggest that the transport mechanism of diamines is similar to that of monoamine compounds in respect to its dependence on ion-diffusion potential and on the membrane surface potential. The extent of the effect of ion-diffusion potential on the rate of transport of the diamines was closely related to the lipophilicity of the diamine. In contrast, only the surface potential contributed to the transport mechanism of lower lipophilic tri- and tetraamine compounds.     

Enantioselective Pharmacokinetics of Homochlorcyclizine: Disposition of (+)- and (–)-Homochlorcyclizine after Intravenous and Oral Administration of Racemic Homochlorcyclizine to Rats

Abstract— Concentrations of homochlorcyclizine enantiomers in blood, urine, and tissues of the liver, lung, kidney, brain, heart, spleen, intestine and stomach of rats after drug administration were determined by high-performance liquid chromatography on a chiral stationary phase. After intravenous administration (10 mg kg^?1), homochlorcyclizine was rapidly distributed in many tissues, with the highest concentration in lung. No differences were found between enantiomers in blood concentrations. After oral administration (50 mg kg^?1), the concentrations of the (+)-isomer in nearly all tissues were higher than those of the (–)-isomer. The AUC_0-x values of the (+)- and (–)-isomers differed significantly. The absorption of racemic homochlorcyclizine from rat small intestine was not enantioselective. These results suggested that the different concentrations between enantiomers after oral administration were not caused by enantioselective absorption or distribution but rather by preferential first-pass metabolism of the (–)-isomer in the liver. The enantioselectivity of metabolism was also demonstrated by in-vitro experiments.     

Concentration gradient of oxalate from cortex to papilla in rat kidney

BACKGROUND: The kidney eliminates the major fraction of plasma oxalate. It is well known that oxalate is freely filtered by glomeruli and secreted by the proximal tubules. However, the renal handling of oxalate in distal nephrons, which is considered as playing an important role in stone formation, remains obscure. METHODS: At 15-180 min after intravenous injection of 14C-oxalate to rats, the intrarenal localization of radioactivity was quantitatively measured by the radioluminographic method using a bioimaging analyzer. Tissue radioactivity was compared with plasma, and urinary radioactivities were measured by a liquid scintillation counter. The control study was conducted with 14C-inulin. RESULTS: The radioactivity of 14C-oxalate in the papilla was 10 times greater than in the cortex and eight times greater than in the medulla 180 min after injection when almost no radioactivity was present in the urine. In contrast, the radioactivity of 14C-inulin was nine times less in the papilla than in the cortex at the same time. CONCLUSION: Oxalate remains in the renal papilla for an extended period. This accumulation of oxalate may be attributed to calcium oxalate crystal fixation along the deep nephron which is considered to be the first step of stone formation.     

U-46619-induced Ischaemic Electrocardiographic Changes in Rats: Preventive Effects of Prostacyclin and Nitroglycerin

Abstract— The anti-anginal effect of nitroglycerin and prostacyclin was examined using, as an index, the ischaemic electrocardiogram (ECG) change (ST elevation) induced by intracoronary arterial injection of 9,11-dideoxy-11α,9α-epoxymethano-PGF_2α (U-46619), a stable thromboxane A₂ agonist, in anaesthetized rats. The ST elevation induced by U-46619 (5–20 μg kg^?1, i.c.a.) was dose-dependent and reproducible. U-46619-induced ST elevation was markedly prevented by the pretreatment of intravenous administration of prostacyclin (0·01 μg kg^?1), and to a lesser extent by nitroglycerin (0·3 mg kg^?1). Simultaneously, platelet count decreased significantly in the coronary arterial blood which indicated that platelet aggregation was enhanced by U-46619. The decrease of platelet count in coronary arterial blood at the time of ST elevation was significantly suppressed by prostacyclin (0·1 μg kg^?1, i.v.), but not by nitroglycerin (0·3 mg kg^?1, i.v.). These results suggest that the ST elevation induced by intracoronary arterial injection of U-46619 may be derived from spasm of coronary artery and platelet aggregation in the intracoronary artery in rats.     

Solitary nodular Langerhans cell histiocytosis

We report a 3-month-old girl with a solitary variant of congenital self-healing reticulohistiocytosis, one type of Langerhans cell histiocytosis.     

Long-term sequential changes of antibody to p40tax in HTLV-I carrier mothers and children

Antibody to p40^tax (anti-p40^tax) in serum specimens obtained sequentially from a human T cell lymphotropic virus type I carrier population of mothers and children were assayed. The prevalences of anti-p40^tax at the initial sampling were 88% (7/8) in children and 55% (16/29) in mothers. Two of the seven positive children lost their anti-p40^tax during the investigation period, resulting in a final prevalence of 63% (5/8) in children. However, anti-p40^tax status was constant in all the 22 mothers with multiple serum samples (15 remained positive and seven remained negative). A decline in the absorbance value of EIA for anti-p40^tax was observed in seven of the 15 anti-p40^tax positive mothers. This decline may result in the disappearance of anti-p40^tax in some of them.     

Accidental transmission of HCV and treatment with interferon

Accidental transmission of contagious pathogens, especially hepatitis C virus (HCV), by needlestick or other means as an occupational hazard for medical staff is of concern. We retrospectively analysed cases of work-related accidental injury with pathogens such as hepatitis B virus (HBV), HCV, syphilis and human immunode?ciency virus (HIV) reported to the centres for disease control at 15 hospitals (total 5776 beds) in the Gunma prefecture, Japan, from December 1990 to August 1993 (24.7 months). There were 416 such cases (16.8 cases/month), with an incidence of 0.2–3.5 accidents per month per hospital. Such accidents occurred in 297 (71.2%) nurses, 98 (23.5%) medical doctors, 13 (3%) laboratory technicians, four (1.0%) hospital maintenance workers, one (0.2%) assistant nurse, one secretary and two others. There were 323 (77.6%) injuries caused by needlestick, 42 (10.1%) from suture needles or surgical knife cuts, 17 (4.1%) from blood splatters from patients into the eyes or mouth, 10 (2.4%) from contact with injured skin and 24 (5.8%) simple skin contacts. Of the pathogens, 60.3% were HCV, 22.6% HBV, 5.8% syphilis, 0.7% HIV and 10.6% were of unknown origin. Four cases (1.6%) of HCV infection were found and treated with one or two courses of interferon therapy, and HCV was subsequently cleared. All four patients were cured with interferon therapy. None of the HBV-injured cases resulted in infection, possibly because of prophylaxis with HB immunoglobulin and HB vaccine. No HIV or syphilis infection was contracted. In summary, chronic HCV infection acquired as an occupational hazard can be cured by appropriate treatment, such as with interferon, after early detection of the infection.