Prospective randomized comparison of mezlocillin therapy alone with combined ampicillin and gentamicin therapy for patients with cholangitis

Forty-six patients with cholangitis were randomized to receive therapy with mezlocillin sodium (24 patients) or a combination of ampicillin sodium--gentamicin sulfate (22 patients). The biliary concentration of mezlocillin was 112 times higher than that of ampicillin and 778 times higher than that of gentamicin. The ratio of the concentration in serum or bile over the minimum inhibitory concentration against aerobic gram-negative bacilli (therapeutic index) was higher for mezlocillin than for either ampicillin or gentamicin. Twenty (83%) of 24 patients were cured following mezlocillin therapy compared with 9 (41%) of 22 patients after ampicillin-gentamicin therapy. The 3 patients with superinfection were in the ampicillin-gentamicin arm of the study. Fewer toxic or adverse effects occurred in association with mezlocillin treatment than with ampicillin-gentamicin treatment. Mezlocillin therapy was more effective, less toxic, and less expensive than treatment with ampicillin and gentamicin for patients with cholangitis.     

18F-FDG PET/CT for detecting nodal metastases in patients with oral cancer staged N0 by clinical examination and CT/MRI.

(18)F-FDG PET has a high accuracy in staging head and neck cancer, but its role in patients with clinically and radiographically negative necks (N0) is less clear. In particular, the value of combined PET/CT has not been determined in this group of patients. METHODS: In a prospective study, 31 patients with oral cancer and no evidence of lymph node metastases by clinical examination or CT/MRI underwent (18)F-FDG PET/CT before elective neck dissection. PET/CT findings were recorded by neck side (left or right) and lymph node level. PET/CT findings were compared with histopathology of dissected nodes, which was the standard of reference. RESULTS: Elective neck dissections (26 unilateral, 5 bilateral; a total of 36 neck sides), involving 142 nodal levels, were performed. Only 13 of 765 dissected lymph nodes harbored metastases. Histopathology revealed nodal metastases in 9 of 36 neck sides and 9 of 142 nodal levels. PET was TP in 6 nodal levels (6 neck sides), false-negative in 3 levels (3 neck sides), true-negative in 127 levels (23 neck sides), and false-positive in 6 levels (4 neck sides). The 3 false-negative findings occurred in metastases smaller than 3 mm or because of inability to distinguish between primary tumor and adjacent metastasis. TP and false-positive nodes exhibited similar standardized uptakes (4.8 +/- 1.1 vs. 4.2 +/- 1.0; P = not significant). Sensitivity and specificity were 67% and 85% on the basis of neck sides and 67% and 95% on the basis of number of nodal levels, respectively. If a decision regarding the need for neck dissection had been based solely on PET/CT, 3 false-negative necks would have been undertreated, and 4 false-positive necks would have been overtreated. CONCLUSION: (18)F-FDG PET/CT can identify lymph node metastases in a segment of patients with oral cancer and N0 neck. A negative test can exclude metastatic deposits with high specificity. Despite reasonably high overall accuracy, however, the clinical application of PET/CT in the N0 neck may be limited by the combination of limited sensitivity for small metastatic deposits and a relatively high number of false-positive findings. The surgical management of the N0 neck should therefore not be based on PET/CT findings alone.     

Policy Perspective on Housing and HIV/AIDS

For persons battling HIV/AIDS a stable place to live may decide the length and quality of life itself. It is nearly impossible for a person on the streets to engage in a needed continuous AIDS treatment regimen when the very basic question of where that person will rest his or her head when darkness comes in just a few hours is unresolved. When danger lurks on the streets, when cold numbs the limbs, when tiredness overwhelms the mind, when fear breaks the spirit, a place to call home would make all the difference.     

Co-operative mineralization and protein self-assembly in amelogenesis: silica mineralization and assembly of recombinant amelogenins in vitro

An amorphous silica mineralization technique was used to produce inorganic/protein composites to elucidate the structure and mechanism of formation of amelogenin assemblies, which may play an important role in regulating enamel structure during the initial stages of amelogenesis. Full-length recombinant amelogenins from mouse (rM179) and pig (rP172) were investigated along with key degradation products (rM166 and native P148) lacking the hydrophilic C terminus found in parent molecules. The resulting products were examined using transmission electron microscopy and/or small-angle X-ray scattering. Using protein concentrations of 0.1–3 mg ml⁻¹, large monodisperse spheres of remarkably similar mean diameters were observed using rM179 (124 ± 4 nm) and rP172 (126 ± 7 nm). These spheres also exhibited 'internal structure', comprising nearly spherical monodisperse particles of ≈ 20 nm in diameter. In the presence of rM166, P148, and bovine serum albumin (control), large unstructured and randomly shaped particles (250–1000 nm) were observed. Without added protein, large dense spherical particles of silica (mean ≈ 500 nm) lacking internal structure were produced. These findings demonstrate that full-length amelogenins have the ability to form higher-order structures, whereas amelogenins that lack the hydrophilic C terminus do not. The results also suggest that full-length amelogenin can guide the formation of organized mineralized structures through co-operative interactions between assembling protein and forming mineral.     

Reactive arthritis and internal derangement of the temporomandibular joint.

OBJECTIVE: The objective of this study was to determine if temporomandibular joint (TMJ) samples positive for Chlamydia trachomatis have a greater presence of tumor necrosis factor-alpha (TNFalpha) or interleukin-6 (IL-6) when compared with Chlamydia-negative samples. STUDY DESIGN: Posterior bilaminar tissue samples removed during TMJ surgery from 70 patients were evaluated. Cryosections were stained using monoclonal antibody that identifies C. trachomatis. The presence of IL-6 and TNFalpha were evaluated by immunostaining in 15 samples positive and in 25 samples negative for the presence of C. trachomatis. RESULTS: Of the 70 TMJ samples, 32 (46%) were positive for C. trachomatis. In 15 samples positive for C. trachomatis, 10 (67%) were positive for TNFalpha and 7 (47%) for IL-6. In 25 samples negative for C. trachomatis, only 4 (16%) were positive for TNFalpha and only 2 (8%) for IL-6. Differences in C. trachomatis-positive samples versus negative were significant for both TNFalpha (P < .002) and IL-6 (P < .008). CONCLUSION: The presence of C. trachomatis in the TMJ is associated with a significantly increased presence of TNFalpha and IL-6.     

Reduced virulence of Candida albicans mutants affected in multidrug resistance.

Disruption of a multidrug resistance gene (CaMDR1) in Candida albicans resulted in mutant strains that colonized mouse kidneys to very high levels but were markedly reduced in their virulence. No obvious differences in several properties related to colonization and dissemination were noted among MDR+ or mdr- strains. These results suggest that specific fungal efflux pumps play a role in fungal pathogenicity.     

Capillary gas chromatographic assay of camphor and m-cresol in dermatological creams

Camphor and m-cresol mixtures are used in antiseptic and anti-itching creams. No compendial method exists for these preparations. This paper reports a capillary gas chromatographic method using FID detection with 2,6-di-tert-butyl-4-methylphenol as internal standard on a 30 m×0.32 mm Supelcowax®-10 column (0.25 μm film) with helium as carrier gas. Ramped temperature programming was applied. The method allows simultaneous quantitation of camphor and m-cresol in the presence of o- and p-cresols, calamine and zinc oxide. Overall percent recoveries (±SD, n=9) of camphor, o-, p- and m-cresol from spiked placebo creams, at a labeled amount of 10 (w/w)% were 96.9±0.6, 98.2±0.6, 99.2±0.5 and 101.0±0.9%, respectively, and at a labeled amount of 1% were 96.7±0.6, 97.8±0.9, 97.8±0.6, and 100.3±1.0%, respectively. The recovery studies were carried out at ±30% of the labeled amounts. Linear peak area or height ratios were obtained (r>0.999) for camphor, o-, p- and m-cresol covering a concentration range of 10–200% of the labeled amount. Linearity (r>0.999) was also obtained for m-cresol when the relative concentration of o- and p-cresol was varied from 5 to 100% of the m-cresol concentration. The resolution between the ‘critical pair’ of p- and m-cresol was ≥1.1. The limit of quantitation was 23 pg for m-cresol and 9.3 pg for camphor using an injection split of 1:50. The repeatability (%RSD) for all compounds were <2% for peak area and <1.4% for peak height ratios. System suitability and robustness of the method were established. The method was successively applied to the assay of available commercial products and allows assay of camphor and the three cresol isomers.     

More-sensitive enzyme-multiplied immunoassay technique for procainamide and N-acetylprocainamide in plasma, serum, and urine

A commercially available (Syva Co.) enzyme-multiplied immunoassay technique (EMIT) for the quantitative determination of procainamide (PA) and N-acetylprocainamide (NAPA) was modified to allow automated quantitative analysis of approximately 100 samples per day, in a working range of 0.1 to 2.0 micrograms/mL. Such a test was needed to evaluate the pharmacokinetic characteristics of controlled-release dosage forms characterized by long half-lives at low plasma concentration. Analytical recovery of PA and NAPA from serum, plasma, and urine was satisfactory, but at extreme ratios for PA:NAPA the accuracy of determining the lower-concentration component became unsatisfactory. In fact, however, we found no such ratios in 5400 clinical samples assayed by this procedure.