Sofosbuvir and daclatasvir combination therapy in a liver transplant recipient with severe recurrent cholestatic hepatitis C.

Recurrent HCV infection following liver transplantation can lead to accelerated allograft injury that is difficult to treat with interferon. The aim of this study is to describe the first ever use of an interferon-free, all oral regimen in a liver transplant recipient with severe recurrent HCV. A 54-year-old male with HCV genotype 1b developed severe cholestatic HCV at 6 months posttransplant with ascites, AST 503 IU/mL, alkaline phosphatase of 298 IU/mL, HCV RNA of 12 000 000 IU/mL, and histological cholestasis with pericellular fibrosis. Sofosbuvir, an HCV polymerase inhibitor (400 mg/day), and daclatasvir, an HCV NS5A replication complex inhibitor (60 mg/day), were co-administered for 24 weeks. Within 4 weeks of initiating treatment, serum HCV RNA levels became undetectable and liver biochemistries normalized with concomitant resolution of ascites. The patient achieved a sustained virological response with undetectable HCV RNA at 9 months posttreatment. During and following treatment, the daily dose and blood level of tacrolimus remained stable and unchanged. The rapid and sustained suppression of HCV replication in this liver transplant recipient provides great promise for the use of combination oral antiviral regimens in other immunosuppressed and interferon refractory HCV patients.

Effects of low-modulus coatings on pin-bone contact stresses in external fixation.

The intent of this study was to investigate the stress distribution in cortical bone around fracture fixation pins and around pins coated with various polymeric and elastomeric materials. Since these interface stresses cannot be measured directly, a photoelastic technique was employed and stresses were measured in two-dimensional bone models fabricated from sheets of epoxy resin. Our results showed that when a fixation pin was loaded in compression, the compressive stress measured in the model was greatest at the pin-model interface. The magnitude of the compressive stress was found to diminish steeply away from the hole in a log decrement distribution which was asymptotic to the value of the average stress in the model. When polymeric and elastomeric materials were applied as pin coatings and the performance of the coated pins was compared to that of uncoated pins of the same overall diameter, a reduction of the maximum stress in the bone model was demonstrated. Among the coatings tested, we found that of the polymeric materials ultrahigh molecular weight polyethylene (UHMWPE) was most effective at reducing the peak cortical stress magnitude. The most effective coating material overall was found to be silicon elastomer. Computation of stress values in models loaded through stainless-steel pins and through pins coated with 1-mm silicon elastomer showed that the presence of the elastomer layer caused a reduction of about 50% in the maximum compressive stress in the model.

"Ratchet-type" marginal fracture of the radial head with locked anterior dislocation. A case report.

Locked anterior dislocation of the superior radioulnar joint occurred in a 26-year-old man. The configuration of the associated radial head fracture maintained the locked position and predisposed to recurrence after open reduction. Radial head excision was necessary to resolve the problem. Both medial ligament repair and a radial head prosthesis were necessary to stabilize the elbow.

Lymphocyte surface IgD and IgM in non-human primates.

IgD was detected on the surface of peripheral blood lymphocytes of five non-human primate species by direct immunofluorescence. The percentages of lymphocytes with surface IgD or IgM were comparable to the percentages reported for humans. The presence of IgD on the surface of rhesus monkey lymphocytes was confirmed by SDS-polyacrylamide gel electrophoresis of immunoprecipitated 125I cell surface protein. Reduced surface IgD was resolved into a light chain component and a heavy chain component whose mobility was identical to that of mu-chain under the condition used.

Effects of clindamycin and gentamicin and other antimicrobial combinations against enterococci in an experimental model of intra-abdominal abscess.

A model was developed to permit direct assessment of antibiotic efficacy against Enterococcus species in experimental intra-abdominal abscess. Abscesses yielded Enterococcus faecalis in pure culture. Antimicrobials were delivered by precisely controlled continuous intravenous infusion. After five days of therapy, ampicillin alone or in combination with gentamicin reduced residual bacterial titers from 7.93 +/- 1.05 (untreated) to 3.51 +/- 1.07 and 3.52 +/- 0.81 log10 colony forming units per gram, respectively. Both the clindamycin and gentamicin combination (6.49 +/- 1.33) and metronidazole and gentamicin combination (6.79 +/- 0.90) significantly suppressed the growth of enterococci (p less than 0.01). Combined clindamycin and aztreonam was ineffective, as were any of the agents used alone (except ampicillin). These results may explain, in part, the clinical efficacy of certain drug combinations against the enterococcal component of polymicrobial abscesses despite the apparent lack of in vitro activity of individual agents.

Treatment of experimental endocarditis caused by a beta-lactamase-producing strain of Enterococcus faecalis with high-level resistance to gentamicin.

Several antimicrobial regimens were evaluated in the treatment of experimental enterococcal endocarditis due to a beta-lactamase-producing, highly gentamicin-resistant strain of Enterococcus faecalis. Ampicillin alone cleared bacteremia in the majority of rats and reduced titers of bacteria within vegetations (6.84 versus 8.80 log10 CFU/g in controls) but did not sterilize valves. Ampicillin-sulbactam combinations, vancomycin, daptomycin, and imipenem each reduced residual bacterial titers within vegetations to 4.01 log10 CFU/g or less; in 26 to 43% of animals receiving 5 days of therapy, titers of bacteria were reduced to undetectable levels. In a separate experiment, rats received ampicillin-sulbactam, daptomycin, or vancomycin for 10 days and were then observed for 10 days after termination of therapy for evidence of relapse. In surviving rats, valves remained sterile in four of five rats treated with ampicillin-sulbactam, in five of seven treated with daptomycin, but in only one of eight receiving vancomycin.