Comparative study of monoclonal antibody scan in diagnosing orthopaedic infection

When clinical data are insufficient to diagnose infection of bone or joints, nuclear scanning becomes crucial in making an accurate diagnosis. The efficacy of (99m)technetium antigranulocyte monoclonal antibody Fab' fragment (LeukoScan) is prospectively compared with (111)indium white blood cell and (99m)technetium methylene diphosphonate bone scans in 74 patients with suspected musculoskeletal infections. They were grouped according to site of suspected infection: 33 long bones, 23 prosthetic joints, and 18 diabetic feet. Sixty-two of these 74 patients had surgical verification with histopathology or culture. The remaining 12 patients had clinical followup as proof of absence of infection. The overall sensitivity of LeukoScan, (111)indium white blood cell, and (99m)technetium methylene diphosphonate bone scans was 93%, 85% and 92%, respectively. Specificity was 89%, 75% and 52%, and accuracy was 90%, 79% and 74%, respectively. The conclusion from this study is that LeukoScan is more accurate in detecting osteomyelitis, with better sensitivity and specificity in prosthetic joints. Compared with (111)indium white blood cell scans, LeukoScan++ gives superior images, and results are obtained in 1 to 6 hours without biohazard risk from handling blood products.     

Consequences of the photodynamic treatment of resting and activated peripheral T lymphocytes

Silencing of the cryptic mating-type loci HMR and HML requires the recognition of DNA sequence elements called silencers by the Sir1p, one of four proteins dedicated to the assembly of silenced chromatin in Saccharomyces cerevisiae. The Sir1p is thought to recognize silencers indirectly through interactions with proteins that bind the silencer DNA directly, such as the origin recognition complex (ORC). Eight recessive alleles of SIR1 were discovered that encode mutant Sir1 proteins specifically defective in their ability to recognize the HMR-E silencer. The eight missense mutations all map within a 17-amino-acid segment of Sir1p, and this segment was also required for Sir1p's interaction with Orc1p. The mutant Sir1 proteins could function in silencing if tethered to a silencer directly through a heterologous DNA-binding domain. Thus the amino acids identified are required for Sir1 protein's recognition of the HMR-E silencer and interaction with Orc1p, but not for its ability to function in silencing per se. The approach used to find these mutations may be applicable to defining interaction surfaces on proteins involved in other processes that require the assembly of macromolecular complexes.     

Effect of multivitamins on plasma homocysteine and folate levels in patients on hemodialysis

Three new triterpene lactones, lancilactones A (1), B (2), and C (3), together with the known kadsulactone A (4), were isolated from the stems and roots of Kadsura lancilimba. Their structures and stereochemistries were determined primarily from mass and NMR spectral data. Compound 3 inhibited HIV replication with an EC50 value of 1.4 microg/mL and a therapeutic index of greater than 71.4.     

Miracidial infectivity of Hypoderaeum conoideum (Trematoda: Echinostomatidae): differential susceptibility of two lymnaeid species

A study was made of the infectivity of Hypoderaeum conoideum miracidia to a range of laboratory-reared specimens of freshwater snail species (Lymnaea peregra, L. corvus, Physella acuta, and Gyraulus chinensis) that coexist with the parasite in the same natural habitat. L. peregra and L. corvus were found to be equally susceptible to the parasite when specimens of each snail species were singly exposed to miracidia. However, when miracidia could choose either lymnaeid species, they showed a high degree of specificity toward L. peregra. The results obtained suggest that H. conoideum miracidia are capable of distinguishing among these lymnaeids in their orientation to the host. This indicates that miracidia might achieve specificity before actually contacting the snail host and suggests that during the host-snail orientation process they respond to signals different from those generated upon snail contact and invasion. The specificity toward L. peregra observed in H. conoideum miracidia seems to indicate adaptation to the snail community in their natural habitat, resulting in enhancement of their transmission.     

Control of glycogen synthesis in cultured human muscle cells

The regulation of glycogen synthesis and associated enzymes was studied in human myoblasts and myotubes maintained in culture. Both epidermal growth factor (EGF) and insulin stimulated glycogen synthesis approximately 2-fold, this stimulation being accompanied by a rapid and stable activation of the controlling enzyme glycogen synthase (GS). EGF also caused inhibition of glycogen synthase kinase 3 (GSK-3) and activation of the alpha isoform of protein kinase B (PKB) with the time-course and magnitude of its effects being similar to those induced by insulin. An inhibitor of the mitogen-activated protein (MAP) kinase pathway did not prevent stimulation of GS by EGF, suggesting that this pathway is not essential for the effect. A partial decrease in the fold activation of GS was, however, observed when p70(S6k) activation was blocked with rapamycin, suggesting a contribution of this pathway to the control of GS by either hormone. Wortmannin, a selective inhibitor of phosphatidylinositol 3'-kinase (PI-3 kinase) completely blocked the effects of both EGF and insulin in these cells. These results demonstrate that EGF, like insulin, activates glycogen synthesis in muscle, acting principally via the PKB/GSK-3 pathway but with a contribution from a rapamycin-sensitive component that lies downstream of PI-3 kinase.     

Prediction of response during interferon alfa 2b therapy in chronic hepatitis C patients using viral and biochemical characteristics: a comparison

Patients with chronic hepatitis C (n = 103) were treated for 24 weeks with interferon alfa 2b and followed up for 24 weeks after cessation of therapy (week 48). When hepatitis C virus (HCV) RNA at week 48 was used to assess interferon response, 15 (14.6%) were virological complete responders, and all have remained HCV RNA negative for a mean of 3 years. At week 48, 3 of 15 virological complete responders had elevated alanine transaminase (ALT) values. When serum ALT level was used at week 48 to determine response to interferon, 20 (19.4%) were biochemical complete responders. However, 8 of the 20 patients with normal ALT levels were HCV RNA positive at week 48, and 7 of these individuals have had a recurrence of elevated ALT levels within 3 years after cessation of treatment. These findings indicate that measurement of HCV RNA was more accurate than ALT in determining true responses to interferon therapy. Identification of nonresponders early during the course of interferon treatment showed that an elevated ALT level at week 12 was 92% predictive (odds ratio 3.7) but misidentified 33% (5 of 15) of the patients who were virological complete responders at week 48. In contrast, a positive HCV RNA at week 12 of treatment was 98% predictive (odds ratio 35.5) and misidentified only 6.7% (1 of 15) of the virological complete responders. Thus, positive HCV RNA at week 12 of therapy was more accurate in identifying eventual virological nonresponders than measurement of ALT at this time. Termination of interferon therapy in patients who were HCV RNA positive at week 12 would result in a 27% reduction in the direct medical costs and keep patients from undergoing unnecessary treatment. Therefore, testing for HCV RNA at week 12 to identify nonresponders and then discontinuing their treatment is practical, cost-efficient and beneficial both to patients and to third-party payers.