The interaction of alcoholic liver disease and hepatitis C

The following article reviews available data of the interaction of alcohol related liver disease and hepatitis C viral infection as well as special considerations for the treatment of these patients. Alcohol worsens the degree and accelerates the progression of hepatic injury, enhances the risk of developing hepatocellular carcinoma and decreases response to interferon therapy. Patients with hepatitis C should avoid alcohol ingestion.     

Stone recurrence after shockwave lithotripsy: possible enhanced crystal deposition in traumatized tissue in rabbit model

The authors present a review of the anatomy of the major bursae around the shoulder joint and discuss the use of the different imaging modalities which demonstrate their radiologic features. The calcified subacromial-subdeltoid bursa has a characteristic appearance on plain radiographs. When inflamed it can be visualized by ultrasound and magnetic resonance imaging. Calcific bursitis may involve the subcoracoid bursa. This bursa may mimic adhesive capsulitis of the shoulder or complete rotator cuff tear when injected inadvertently during shoulder arthrography. Less well known are three coracoclavicular ligament bursae. These are also subject to calcific bursitis and have a typical radiologic appearance.     

Ultrarapid drug metabolism: PCR-based detection of CYP2D6 gene duplication

The enzyme debrisoquine 4-hydroxylase (CYP2D6), which metabolizes many widely used drugs, is highly polymorphic. The activity of the enzyme ranges between subjects from ultrafast to a complete absence. Therefore, metabolic capacity varies, producing intersubject differences in therapeutic efficacy and side effects at standard recommended doses. Up to 7% of Caucasians may demonstrate ultrarapid drug metabolism (UM) because of inherited alleles with multiplicate functional CYP2D6 genes, causing an increased amount of enzyme to be expressed. Identification of UM subjects is of potential clinical importance for adjustment of doses in drug therapy, as well as to avoid misidentification of noncompliance. In our study, we tested recently designed PCR assays for the detection of the UM genotype. We found a 3.5% prevalence of UMs carrying duplicate active CYP2D6 genes in a population consisting of 202 psychiatric patients.     

Increased levels of proteoglycan fragments and stromelysin in hip joint fluid in Legg-Calvé-Perthes disease

High response rates in patients with metastatic melanoma have been achieved with combination chemoimmunotherapy. A response rate of 62% in 45 patients has been reported for treatment with dacarbazine, bleomycin, vincristine, lomustine (BOLD) plus interferon alpha (IFN-alpha). We conducted a multicentre phase II study to confirm these results. Melanoma patients with distant metastases were treated as outpatients with dacarbazine 200 mg m(-2) on days 1-5, vincristine 1 mg m(-2) on days 1 and 4, bleomycin 15 mg on days 2 and 5 i.v. and lomustine 80 mg orally on day 1, repeated every 4 weeks. IFN-alpha-2b was initiated s.c. on day 8 at 3 MU daily for 6 weeks, and 6 MU t.i.w. thereafter. Forty-three patients entered the study. The median number of metastatic sites was three (range 1-5), and 81% of patients had visceral metastases. Nine patients had brain metastases, and seven patients were systemically pretreated. Among the 41 patients that were evaluable for response, the response rate was 27% (95% CI 14-3%), with one complete and ten partial remissions. The response rate in 25 previously untreated patients without brain metastases was 40% (95% CI 21-61%). Median duration of response was 6 (range 2-14+) months; median overall survival was 5 (1-26) months. The main toxicity was malaise/fatigue. We confirm that BOLD plus IFN-alpha has activity in metastatic melanoma. The lower response rate in our study compared with the previous report is probably related to patient selection, as in the previous study 46% of patients had stage III disease, whereas all our patients had stage IV disease, which is associated with a worse prognosis.     

Brownian motion on a square Lennard-Jones lattice: Trapping, hopping, and diffusion

Previously we showed that cGMP hydrolysis in rat whole retinal homogenates exhibited a dose-dependent inhibition following developmental lead exposure and a concentration-dependent inhibition with direct Pb2+ exposure. Additionally, developmental lead exposure resulted in a dose-dependent increase in retinal cGMP and rod Ca2+ levels. To determine whether Pb2+ or Ca2+ directly inhibited the rod-specific cGMP phosphodiesterase (PDE) and to examine the kinetic mechanism of this inhibition, purified bovine rod cGMP PDE was assayed in the presence of varying concentrations of cGMP, and Mg2+, Pb2+, and/or Ca2+. Increasing concentrations of the substrate, cGMP, resulted in a shift of the Pb2+ and Ca2+ concentration-response curves to the left, indicating a decrease in the half-maximal inhibitory concentrations of Pb2+ from nanomolar to picomolar levels. Increasing concentrations of the cofactor, Mg2+, resulted in a shift of the Pb2+ and Ca2+ concentration-response curves to the right, indicating a decrease in the inhibition of PDE activity by Pb2+ or Ca2+. A plot of 1/velocity vs 1/Mg2+ as a function of Pb2+ revealed that picomolar concentrations of Pb2+ competitively inhibited PDE relative to millimolar concentrations of Mg2+. Consistent with this finding, Mg2+ reversed the Pb(2+)-induced inhibition of PDE. Our recent kinetic analysis showed that Mg2+ and cGMP bind at interacting sites on the PDE in a random order. The present results reveal that Pb2+ may bind at the same site but with 4-6 log units higher affinity than Mg2+, thus preventing the hydrolysis of cGMP. These findings provide a novel mechanism for understanding the Pb(2+)-induced inhibition of cGMP PDE. These results may have implications for other enzymes using Mg2+ as a cofactor and suggest that Mg2+ may be useful in these situations for reversing the inhibition by Pb2+.     

Evaluation of an educational program for asthma control in adults

We have developed a 6-month educational plan associated with outpatient follow-up and special clinical care for asthmatic patients in a deprived population, with serious socioeconomic problems and a very low level of education. The objective was to determine the effects of the program on clinical asthma outcomes, lung function, and quality of life. Forty patients were enrolled in the program with a regular schedule of outpatient visits, and 31 finished the 6-month intervention, which included information about asthma, instruction in appropriate use of medication, training in metered-dose inhaler technique, how to identify and control asthma triggers, how to use symptom diary cards, and how to recognize early signs of deterioration. Patients included 8 males and 23 females, 47.8 +/- 16.5 years old, with 77.4% elementary school education and 22.6% illiterate, and an average monthly income of around $450. After the 6-month program there was a significant change in asthma control with a reduction in asthma emergency visits and hospitalization, reduction of score symptoms, and improvement in quality of life. Based on the results, educational programs are recommended and should be adapted to the socioeconomic and cultural characteristics of the target population.     

A new skeleton bisditerpenoid alkaloid from Aconitum pukeense]

A novel bisditerpenoid alkaloid named pukeensine was isolated from Aconitum pukeense W. T. Wang (Ranunculaceae). Its proposed structure was suggested by spectral evidence. This bisditerpenoid alkaloid skeleton has not been found previously.