Ceftriaxone once daily for four weeks compared with ceftriaxone plus gentamicin once daily for two weeks for treatment of endocarditis due to penicillin-susceptible streptococci. Endocarditis Treatment Consortium Group

This randomized, multicenter, open-label study compared the efficacy and safety of monotherapy with 2 g of intravenous ceftriaxone once daily for 4 weeks with those of combination therapy with 2 g of intravenous ceftriaxone and 3 mg of intravenous gentamicin/kg once daily for 2 weeks as therapy for endocarditis due to penicillin-susceptible streptococci. Sixty-one patients were enrolled in the study. Clinical cure was observed for 51 evaluable patients both at termination of therapy and at the 3-month follow-up: 25 (96.2%) of 26 monotherapy recipients and 24 (96%) of 25 combination therapy recipients. Of the 23 patients in each treatment group who were microbiologically evaluable, 22 (95.7%) in each group were considered cured. No patient had evidence of relapse. Fourteen patients (27.5%) required cardiac surgery after initiation of treatment, including five monotherapy recipients and nine combination therapy recipients. Adverse effects were minimal in both treatment groups. We conclude that 2 g of ceftriaxone once daily for 4 weeks and 2 g of ceftriaxone in combination with 3 mg of gentamicin/kg once daily for 2 weeks are both effective and safe for the treatment of streptococcal endocarditis.     

Amoxicillin and clavulanic acid concentrations in gingival crevicular fluid

The beta-lactams are bactericidal antibiotics, but some of them may be inactivated by bacterial beta-lactamases which destroy the beta-lactam ring. The inactivation of amoxicillin by beta-lactamases of gram negative anaerobic bacteria can be circumvented by the addition of clavulanic acid, a beta-lactamases inhibitor. Thus, most of these bacteria are susceptible to this combination. The aim of this study was to investigate the concentrations of amoxicillin and clavulanic acid in gingival crevicular fluid (GCF). These concentrations were measured in 20 patients with rapidly progressive periodontitis 1 h after a dose of 500 mg (1 tablet Augmentin) on day 0 and 1 h after the 10th intake on day 3. For the sampling of GCF, Periopapers were introduced in 16 gingival sites per subject and time. The GCF volumes collected were estimated using the Periotron 6000. A high performance liquid chromatography method has been developed for the determination of amoxicillin and clavulanic acid in microsamples (1 to 10 microliters) of GCF. The concentrations of amoxicillin and clavulanic acid were respectively, 14.05 micrograms ml-1 and 0.40 microgram ml-1 at day 0, 13.93 micrograms ml-1 and 0.37 microgram ml-1 at day 3. Effective levels of amoxicillin and clavulanic acid, well above the minimal inhibitory concentrations of some susceptible periodontal anaerobes (P. intermedia) involved in destructive periodontal diseases, are achieved following the multiple administration of amoxicillin combined with clavulanic acid.     

Antibacterial protection of suture material by chlorhexidine-functionalized polyelectrolyte multilayer films

The formation of bacterial biofilms on the surface of implanted materials is a critical factor that may lead to chronic microbial infection and tissue necrosis. In the present study we analysed the stability of polyelectrolyte multilayer (ML) films on suture materials and the antibacterial effect obtained with chlorhexidine (CHX)-functionalized films built on different types of suture materials such as silk, polyester and copolymer of glycolide and l-lactide. The comparison of Escherichia coli culture on glass coverslips and glass coverslips with ML and CHX showed at 24 h an inhibition of the bacterial relative luminescence (40.68%, P < 0.5) and at 48 h (99.46%, P < 0.001). In another way, simple soaking of suture material overnight in CHX digluconate 20% without polyelectrolyte films did not at all protect sutures from bacterial colonization but CHX-functionalized polyelectrolyte films, made from poly-l-glutamic acid and poly-l-lysine, inhibited Escherichia coli proliferation. Youssef Haikel and Constant Vodouhê contributed in an equal way to the management of the project.     

Research in Computational Design at Stanford

With contributions from J-C. Latombe, T.O. Binford, M. Genesereth, B. Hayes-Roth, T. Gruber, L. Leifer, and R.E. Levitt.     

Involvement of human intracisternal A-type retroviral particles in autoimmunity

Prior studies have linked retroviruses to various arthropathies and autoimmune diseases. Sj?gren's syndrome (SS), a systemic autoimmune disease, is characterized by aggressive infiltration of lymphocytes into the salivary and lacrimal glands, resulting in destruction of the glands and dry mouth and eyes (sicca syndrome). The infiltrating lymphocytes in SS may become overtly malignant, and thus, the incidence of lymphoma is greatly increased in SS patients. A human intracisternal A-type retroviral particle type I (HIAP-I) has been isolated from persons with SS. HIAP-I shares a limited number of antigenic epitopes with human immunodeficiency virus (HIV), but is distinguishable from HIV by morphological, physical, and biochemical criteria. A substantial majority of patients with SS or systemic lupus erythematosus (SLE) have serum antibodies to the proteins of this human retrovirus. Fewer than 3% of the normal blood donor population have antibodies to any HIAP-associated proteins. A second type of a human intracisternal A-type retrovirus, HIAP-II, was detected in a subset of patients with idiopathic CD4 lymphocytopenia (ICL), an AIDS-like immunodeficiency disease. Most HIAP-II positive ICL patients were also antinuclear antibody positive. Reviewed here are additional studies from several laboratories suggesting that HIAP or related viruses may be involved in SLE and other autoimmune conditions. Additionally, results of comprehensive surveys of autoimmune patients to determine seroreactivity to HIAP, and other human retroviruses, including HIV and human T-lymphotropic virus type I, are reported.     

Coronary calcium measurements by double helical computed tomography. Using the average instead of peak density algorithm improves reproducibility

RATIONALE AND OBJECTIVES: Coronary calcium (CC) measured by fast computed tomography (CT) was proposed recently as a noninvasive method of monitoring the coronary atherosclerotic process. Assessment of the reproducibility of CC measurements (mainly interstudy variability) is essential for consistent interpretation of serial studies. METHODS: The authors scanned 74 patients (50 men and 24 women) twice on the same day to determine the interstudy variability of a new scoring algorithm, using the average instead of conventional peak CT density values. RESULTS: Nineteen patients had no calcium on either scan. In the remaining 55 patients, interstudy variability was decreased by 31% using the average algorithm (32%-23%; P < 0.001). CONCLUSIONS: Using the average instead of conventional peak density score provides better reproducible measurements of calcium by double helical CT.