Liver transplantation for chronic hepatitis B with lamivudine-resistant YMDD mutant using add-on adefovir dipivoxil plus lamivudine.

Lamivudine treatment in patients with chronic hepatitis B virus (HBV) infection may improve clinical state and suppress viral replication before liver transplantation. Emergence of lamivudine-resistant YMDD mutant is common. We report the results of liver transplantation in 16 patients with pretransplantation YMDD mutants after receiving lamivudine treatment for a median of 738 days (range, 400-1799 days). Adefovir dipivoxil (10 mg daily) was added on to lamivudine for a median of 20 days (range, 8-271 days) before (n = 11) or at (n = 5) liver transplantation, and the combination was continued indefinitely thereafter. Eight patients received additional intravenous hepatitis B immune globulin (HBIG) for a median of 24 months. Fifteen patients with known pre-adefovir HBV DNA levels had a median titer of 14,200 x 10(3) copies/mL (2 x 10(3) to 4,690,000 x 10(3) copies/mL), and 14 had HBV DNA >10(5) copies/mL. All but 1 patient remained positive for HBV DNA (by quantitative polymerase chain reaction [qPCR]) at the time of liver transplantation, and the titer was greater than10(5) copies/mL in 8 patients. The median follow-up after liver transplantation was 21.1 (range, 4.4-68.9) months. One patient (6%) died of an unrelated cause 12.2 months after transplantation, and 15 patients (94%) were alive with the original graft. All patients cleared HBV DNA and had no detectable HBV DNA by qPCR at the latest follow-up. Fourteen patients had cleared hepatitis B surface antigen (HBsAg), but 2 patients who received only adefovir dipivoxil and lamivudine without HBIG remained HBsAg positive after 7.7 and 9.5 months. Serum HBV DNA, however, was negative, and there was no biochemical or histological evidence of recurrence. Adefovir dipivoxil was well tolerated with no significant renal toxicity. In conclusion, a combination of add-on adefovir dipivoxil plus lamivudine therapy provides effective prophylaxis in patients with pretransplantation YMDD mutant that may be actively replicating. The cost effectiveness of additional passive immunoprophylaxis remains to be defined.     

Superiority of intravesical immunotherapy with Corynebacterium parvum and Allium sativum in control of murine bladder cancer

Intravesical immunotherapy with bacillus Calmette-Guerin (BCG), Corynebacterium parvum (CP), keyhole limpet hemocyanin (KLH), and an extract of Allium sativum (AS) was studied in mice transplanted intravesically with mouse bladder tumor cells (MBT-2). Female C3H/He mice were anesthetized with sodium pentobarbital. Two X 10(5) MBT-2 cells were delivered into the bladder transurethrally using a small catheter, immediately after the posterior wall of the bladder had been electrocauterized. Bladder tumor became palpable or demonstrable microscopically in two weeks. Immunotherapy with BCG (2 X 10(6) CFU), CP (250 micrograms), KLH (50 micrograms), or AS (25 mg) was administered directly into the bladder via urethral catheter on day 1, day 6, or days 1 and 6. On day 21 the bladders and spleens were excised and weighed, and the bladders were examined macroscopically and microscopically for evidence of tumor. The results of the study showed that two treatments given one and six days after tumor transplant yielded the lowest tumor incidence and that CP and AS appeared equally effective or even slightly more effective than BCG in this model. These results suggest that clinical evaluation of CP or AS may be worthwhile.     

Allium sativum (garlic) inhibits lipid synthesis by Candida albicans.

The effect of aqueous garlic extract on the macromolecular synthesis of Candida albicans was studied. Protein and nucleic acid syntheses were inhibited to the same extent as growth, but lipid synthesis was completely arrested. Blockage of lipid synthesis is likely an important component of the anticandidal activity of garlic.     

Rate-responsive pacing with a pacemaker that detects respiratory rate (Biorate): clinical advantages and complications

The respiratory-dependent pacemaker (RDP3 or MB-1, Biorate, Biotec International, S.p.A., Bologna, Italy) detects the respiratory rate by measuring thoracic impedance using a subcutaneous auxiliary lead. The sensed respiratory rate is used to determine the pacing rate response. This pacemaker had been implanted in 9 patients with a mean age of 58 (range 42-69) years. During symptom-limited treadmill exercise, rate-modulated pacing resulted in a significant increase in pacing rate (mean +/- SD, 124 +/- 10 vs. 71 +/- 3 beats/min p less than 0.001) and exercise capacity (343 +/- 147 vs. 463 +/- 120 s, p less than 0.05) compared to those achieved with constant rate ventricular pacing. Brief treadmill exercise tests showed appropriate rate response to increased walking speed and gradient. However, rate response was modified by arm swinging-induced motion artefact which affected the measured "impedance." Complications observed on follow-up included perforation of the auxiliary lead in 2 patients and symptomatic myopotential interference in 3 patients with the RDP3 pacemaker, all of whom required unit replacement. It is concluded that although the respiratory-dependent pacemaker can confer physiological benefit in patients with bradycardia, myopotential interference (largely overcome by the new version MB-1 with programmable sensitivity) and the auxiliary lead can be problematic in some patients.     

Pre-operative parenteral nutrition in patients with oesophageal cancer: a prospective, randomised clinical trial

A prospective randomised clinical trial was conducted to examine the efficacy of 2 weeks pre-operative parenteral nutrition (PPN) for the prevention of complications following surgery for oesophageal cancer. Forty patients were studied, the diet of twenty being supplemented by pre-operative parenteral nutrition. There were no significant differences in age, nutritional status, tumour staging and histology between the two groups of patients. The use of PPN resulted in a significant gain in body weight and nitrogen but failed to produce an overall reduction in post-operative morbidity and mortality rates. However patients receiving PPN exhibited two types of changes in serum albumin levels. Those with a fall in serum albumin levels associated with an increase in body weight (indicating an expansion of extracellular volume) had a significantly higher incidence of post-operative pulmonary complications than the group exhibiting a rise in serum albumin levels concomitant with increase in body weight. These data suggested that two weeks PPN might not be adequate in certain patients and a longer period of PPN is required. They also show no clinical benefit from the routine use of pre-operative parenteral nutrition in all patients, but do not exclude benefit in selected groups.     

Presence and characterization of extraintestinal pathogenic Escherichia coli virulence genes in F165-positive E. coli strains isolated from diseased calves and pigs

The virulence genotype profile and presence of a pathogenicity island(s) (PAI) were studied in 18 strains of F165-positive Escherichia coli originally isolated from diseased calves or piglets. On the basis of their adhesion phenotypes and genotypes, these extraintestinal pathogenic strains were classified into three groups. The F165 fimbrial complex consists of at least two serologically and genetically distinct fimbriae: F165(1) and F165(2). F165(1) is encoded by the foo operon (pap-like), and F165(2) is encoded by fot (sfa related). Strains in group 1 were foo and fot positive, strains in group 2 were foo and afa positive, and strains in group 3 were foo positive only. The strains were tested for the presence of virulence genes found mainly in extraintestinal pathogenic E. coli (ExPEC) strains. Although all the strains were positive for the papA variant encoding F11 fimbriae incD, traT, and papC, the prevalence of virulence genes commonly found in PAIs associated with ExPEC strains was highly variable, with strains of group 2 harboring most of the virulence genes tested. papG allele III was detected in all strains in group 1 and in one strain in group 3. All other strains were negative for the known alleles encoding PapG adhesins. The association of virulence genes with tRNA genes was characterized in these strains by using pulsed-field gel electrophoresis and DNA hybridization. The insertion site of the foo operon was found at the pheU tRNA locus in 16 of the 18 strains and at the selC tRNA locus in the other 2 strains. Furthermore, 8 of the 18 strains harbored a high-pathogenicity island which was inserted in either the asnT or the asnV/U tRNA locus. These results suggest the presence of one or more PAIs in septicemic strains from animals and the association of the foo operon with at least one of these islands. F165-positive strains share certain virulence traits with ExPEC, and most of them are pathogenic in piglets, as tested in experimental infections.     

A chronic mouse model of Parkinson's disease has a reduced gait pattern certainty

The purpose of this investigation was to determine if a chronic Parkinson's disease mouse model will display less certainty in its gait pattern due to basal ganglia dysfunction. A chronic Parkinson's disease mouse model was induced by injecting male C57/BL mice with 10 doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (25 mg/kg) (MPTP) and probenecid (250 mg/kg) (P) over 5 weeks. This chronic model produces a severe and persistent loss of nigrostriatal neurons resulting in dopamine depletion and locomotor impairment. The control mice were treated with probenecid alone. Fifteen weeks after the last MPTP/P treatment, the mice were videotaped in the sagittal plane with a digital camera (60 Hz) as they ran on a motorized treadmill at a speed of 10 m/min. The indices of gait and gait variability were calculated. Stride length was significantly (p = 0.016) more variable in the chronic MPTP/P mice. Additionally, the chronic MPTP/P mice had a statistically less certain gait pattern when compared to the control mice (p = 0.02). These results suggest that variability in the gait pattern can be used to evaluate changes in neural function. Additionally, our results imply that disorder of the basal ganglia results in less certainty in modulating the descending motor command that controls the gait pattern.     

Biological Activity of a Partially Purified Inhibitor of Vaccinia Virus Hemagglutinin

An inhibitor acting against vaccinia virus hemagglutinin, and producing a hemagglutinin-negative virus, was separated from tumorous ascitic plasma. The finding that the partially purified inhibitor was biologically active strengthens the evidence for a specific role of the inhibitor in altering the virus.