Effect of hepatic cirrhosis on the pharmacokinetics of theophylline in rats

The experimental hepatic cirrhosis was induced either by bile duct ligation (BDL) or by pretreatment with dimethylnitrosamine (DMNA). The pharmacokinetics of theophylline were studied after a single intravenous or a single oral administration. Using the ultrafiltration method, protein-drug binding experiments were also carried out. The bilirubin level was several-fold increased by BDL, but not by DMNA treatment. The albumin content was decreased in both cirrhotic groups. The total clearance (Clt, ml/kg/hr) of theophylline in both hepatic cirrhosis groups significantly decreased and the terminal half-life (t_1/2) in the cirrhotic rats was increased about two-fold after intravenous and oral administration. The volume of distribution at steady state (Vdss, ml/kg) was increased slightly in the cirrhotic groups. Protein binding in BDL (8.67±4.85%) decreased about four-folds, but in DMNA (73.00±9.85%) similar result, was observed as compared with the control. Increased free fraction of theophylline did not increase the volume of distribution in BDL. Therefore decreased total body clearance of theophylline was mainly due to decreased intrinsic clearance of theophylline in the liver. The absolute bioavailability of theophylline in these experiments was between 63.8 and 72.8%(66.1% in BDL, 63.8% in Sham operated and Control, 72.8% in DMNA). These results suggest that in the experimental hepatic cirrhosis model, administration route does not affect the disposition of theophylline.     

Ginsenoside Rs3, a genuine dammarane-glycoside from Korean red ginseng

A genuine dammarane-glycoside, named as ginsenoside Rs₃, was isolated from the MeOH extracts of Korean red ginseng (Panax ginseng C.A. Meyer) through repeated silica gel column chromatographies and its chemical structure was determined as (20S)-protopanaxadiol 3-O-[6″-O-acetyl-β-D-glucopyranosyl (1→2)-β-D-glucopyranoside on the basis of several spectral and physical evidences including HMBC and FAB-MS.     

Postoperative adjuvant therapy for stage II non-small-cell lung cancer

BACKGROUND: Stage II non-small-cell lung cancer is regarded as one of the early lung cancers. Although resection, including the mediastinal lymph nodes, is currently regarded as the standard treatment, the survival rate of this disease is not encouraging. It is well known that the most common causes of death are locoregional recurrences or distant metastases, or both. However, the best adjuvant treatment to improve survival is as controversial an issue as ever. METHODS: This study was designed as a randomized, blinded, two-armed study with operation and adjuvant radiotherapy in one arm, versus operation and adjuvant mitomycin C (10 mg/m2), vinblastine (6 mg/m2), and cisplatin (100 mg/m2) (MVP) chemotherapy in the other arm. We assigned 57 resected patients with pathologic proven stage II non-small cell lung cancer to the groups according to our eligibility criteria. RESULTS: The most common pattern of recurrence was distant metastases, and nearly all the recurrences (17 of 18 patients) in both groups were found within 2 years after operation. The rates of the locoregional and distant metastases were 3.6% and 46.4% in the adjuvant radiotherapy group and 6.9% and 10.3% in the adjuvant chemotherapy group (p = 0.018). The 5-year disease-free survival rates were 52.0% in the adjuvant radiotherapy group and 74.0% in the adjuvant chemotherapy group (p = 0.16, log-rank test). The 2-year, 5-year, and 6-year survival portions were 60.3%, 56.5%, and 28.3% in the adjuvant radiotherapy group, and 82.8%, 70.1%, and 60.1% in the adjuvant chemotherapy group (p = 0.01, p = 0.17, and p = 0.03, Z-test). The difference of the actuarial survival between these two groups was somewhat significant (p = 0.09, log-rank test). CONCLUSIONS: Our results suggest that the addition of adjuvant MVP chemotherapy may reduce the distant metastasis rates and prolong the survival of the surgically resected stage II non-small-cell lung cancer patients.     

Transfer of extensor carpi radialis longus or brevis for opponensplasty

For the restoration of thumb opposition many types of tendon transfer techniques have been described. The flexor digitorum superficialis (FDS) of the ring finger is commonly selected as a motor. On occasion, however, the quality of the flexor muscles of the fingers or wrist is not good enough for tendon transfer and another available muscle must be selected. In this situation, we have preferred to use an extensor carpi radialis longus (ECRL) or brevis (ECRB) transfer to restore opposition of the thumb. Follow-up examination, at an average 5 years and 10 months after operation, showed that the results of ten of 11 transfers were excellent and the other was good.     

Nosocomial respiratory syncytial virus infection in Canadian pediatric hospitals: a Pediatric Investigators Collaborative Network on Infections in Canada Study

OBJECTIVE: To determine nosocomial transmission of respiratory syncytial virus (RSV) in Canadian pediatric hospitals, outcomes associated with nosocomial disease, and infection control practices. DESIGN: A prospective cohort study in the 1992 to 1994 winter respiratory seasons. SETTING: Nine Canadian pediatric university-affiliated hospitals. PARTICIPANTS: Hospitalized children with symptoms of lower respiratory tract infection (at least one of cough, wheezing, dyspnea, tachypnea, and apnea) and RSV antigen identified in a nasopharyngeal aspirate. RESULTS: Of 1516 children, 91 (6%) had nosocomial RSV (NRSV), defined as symptoms of lower respiratory tract infection and RSV antigen beginning >72 hours after admission. The nosocomial ratio (NRSV/[com-munity-acquired RSV {CARSV})] + NRSV) varied by site from 2.8% to 13%. The median length of stay attributable to RSV for community-acquired illness was 5 days, but 10 days for nosocomial illness. Four children with NRSV (4. 4%) died within 2 weeks of infection, compared with 6 (0.42%) with CARSV (relative risk = 10.4, 95% confidence interval: 3.0, 36.4). All sites isolated RSV-positive patients in single rooms or cohorted them. In a multivariate model, no particular isolation policy was associated with decreased nosocomial ratio, but gowning to enter the room was associated with increased risk of RSV transmission (incidence rate ratio 2.81; confidence interval: 1.65, 4.77). CONCLUSIONS: RSV transmission risk in Canadian pediatric hospitals is generally low. Although use of barrier methods varies, all sites cohort or isolate RSV-positive patients in single rooms. Children with risk factors for severe disease who acquire infection nosocomially have prolonged stays and excess mortality.