Subcutaneous and intravenous ceftriaxone administration in patients more than 75 years of age.

OBJECTIVE: We wanted to compare the first line intravenous administration of ceftriaxone to a subcutaneous administration in patients more than 75 years of age. METHOD: We performed a retrospective monocentric study on all patients more than 75 years of age admitted to the Ales hospital between January 1 and December 31, 2011, having received at least two doses of ceftriaxone intravenously (IV) or subcutaneously (SC). RESULTS: One hundred and forty-eight patients (70 females/78 males patients) were included, 110 received ceftriaxone IV and 38 SC. They were a mean age of 84.7 years, older in the SC group (86.9 years) than in the IV group (83.9 years) (P = 0.0052). The SC group patients presented more frequently with dementia (57% vs. 25% P = 0.001), were more often bedridden (22% vs. 7% P = 0.023), had a higher mean World Health Organization status (3.13 vs. 2.76, P = 0.0181), and higher ADL score (7.79 vs. 5.76, P = 0.0056). There was no statistical difference for isolated bacteria, site of infection, death rate, and patients cured. CONCLUSION: Subcutaneous ceftriaxone administration seems to be preferred for fragile elderly patients independently of disease severity. This administration is not associated to an impaired effectiveness or to an increased death rate.

Least-squares dual characterization for ROI assessment in emission tomography.

Our aim is to describe an original method for estimating the statistical properties of regions of interest (ROIs) in emission tomography. Drawn upon the works of Louis on the approximate inverse, we propose a dual formulation of the ROI estimation problem to derive the ROI activity and variance directly from the measured data without any image reconstruction. The method requires the definition of an ROI characteristic function that can be extracted from a co-registered morphological image. This characteristic function can be smoothed to optimize the resolution-variance tradeoff. An iterative procedure is detailed for the solution of the dual problem in the least-squares sense (least-squares dual (LSD) characterization), and a linear extrapolation scheme is described to compensate for sampling partial volume effect and reduce the estimation bias (LSD-ex). LSD and LSD-ex are compared with classical ROI estimation using pixel summation after image reconstruction and with Huesman's method. For this comparison, we used Monte Carlo simulations (GATE simulation tool) of 2D PET data of a Hoffman brain phantom containing three small uniform high-contrast ROIs and a large non-uniform low-contrast ROI. Our results show that the performances of LSD characterization are at least as good as those of the classical methods in terms of root mean square (RMS) error. For the three small tumor regions, LSD-ex allows a reduction in the estimation bias by up to 14%, resulting in a reduction in the RMS error of up to 8.5%, compared with the optimal classical estimation. For the large non-specific region, LSD using appropriate smoothing could intuitively and efficiently handle the resolution-variance tradeoff.

A heuristic statistical stopping rule for iterative reconstruction in emission tomography.

OBJECTIVE: We propose a statistical stopping criterion for iterative reconstruction in emission tomography based on a heuristic statistical description of the reconstruction process. METHODS: The method was assessed for MLEM reconstruction. Based on Monte-Carlo numerical simulations and using a perfectly modeled system matrix, our method was compared with classical iterative reconstruction followed by low-pass filtering in terms of Euclidian distance to the exact object, noise, and resolution. The stopping criterion was then evaluated with realistic PET data of a Hoffman brain phantom produced using the GATE platform for different count levels. RESULTS: The numerical experiments showed that compared with the classical method, our technique yielded significant improvement of the noise-resolution tradeoff for a wide range of counting statistics compatible with routine clinical settings. When working with realistic data, the stopping rule allowed a qualitatively and quantitatively efficient determination of the optimal image. CONCLUSIONS: Our method appears to give a reliable estimation of the optimal stopping point for iterative reconstruction. It should thus be of practical interest as it produces images with similar or better quality than classical post-filtered iterative reconstruction with a mastered computation time.

Place of (18)F-FDG-PET with computed tomography in the diagnostic algorithm of patients with fever of unknown origin.

There is evidence for the interest of (18)F-fluoro-deoxyglucose positron emission tomography with computed tomography ((18)F-FDG-PET/CT) in fever of unknown origin (FUO) clinical investigation. However, little and conflicting data exist about its place in the investigation procedure. The aim of this work was to evaluate the clinical value of (18)F-FDG-PET/CT in patients with FUO and identify patients who need early (18)F-FDG-PET/CT rather than a last-resort procedure. We performed a 2-year retrospective cohort study at the Nîmes University Hospital, France. A total of 79 patients (36 men, 43 women, mean age 54.0 ± 16.2 years) with FUO underwent (18)F-FDG-PET/CT. A final diagnosis was established in 61 (77.2 %) cases. Aetiologies of FUO were determined using (18)F-FDG-PET/CT findings in 45 (73.8 % of patients with diagnosis) cases. The sensibility and specificity value were 98 % and 87 %, respectively. The presence of adenopathy, low haemoglobin and increased C-reactive protein (CRP) were predictors of high-yield (18)F-FDG-PET/CT. (18)F-FDG-PET/CT may help to detect most causes of FUO. The predictors of high-yield (18)F-FDG-PET/CT found in this study can help identify patients likely to benefit from specific and early imaging techniques.

Diabetic foot infection: a critical review of recent randomized clinical trials on antibiotic therapy.

Controlled clinical trials are essential tools for evaluating the efficacy of antibiotic treatment against infection, but the results of such trials critically depend on sensitive, reproducible, and feasible outcome measures. We reviewed randomized controlled trials on the antibiotic treatment of diabetic foot infection published between 1999 and 2009 in terms of quality and endpoints. Discrepancies in study design, inclusion criteria, statistical methodology, and the varying definitions of both clinical and microbiological endpoints between the published studies, make it difficult to compare them, as well as to determine which regimen may be the most appropriate for patients with diabetic foot infection.

Long-term outcome of chronic hepatitis C in a population-based cohort and impact of antiviral therapy: a propensity-adjusted analysis.

This population-based study aimed to assess the determinants of the outcome of chronic hepatitis C with analysis of the impact of antiviral therapy with or without sustained virological response (SVR) on cirrhosis decompensation, hepatocellular carcinoma, liver-related and non-liver-related mortality. A total of 1159 HCV-positive patients newly detected between 1994 and 2001 were included. For each outcome, the prognostic effect of patients' baseline characteristics was estimated by time-dependent Cox models using age as the time-scale and adjusting for treatment received during follow-up. The impact of antiviral therapy was assessed by using a propensity score in a sample including 184 patients treated in the first 24 months following diagnosis who were matched to 184 untreated patients. At the end of a 59-month median follow-up, 100 cases of compensated disease, 58 liver cancer and 163 deaths (55 liver related) were recorded. The 5-year rates of decompensated cirrhosis, hepatocellular carcinoma, liver-related and non-liver-related death were 4.4%, 2.7%, 5.0% and 8.9%, respectively. Multivariate analyses identified two variables with pejorative influence: alcohol consumption (RR = 4.29 for CD; RR = 5.76 for HCC; RR = 6.69 for liver-related death; P < 0.0001); HCV diagnosis unrelated to systematic screening (RR = 2.25 for CD; RR = 3.05 for HCC; RR = 4.31 for liver-related death, P < 0.03). In the matched subset, no significant benefit of antiviral therapy was observed. Nevertheless, among the 144 patients who achieved SVR, no death was observed. This population-based study showed substantial rates of decompensated cirrhosis, hepatocellular carcinoma and non-liver-related mortality. Alcohol consumption and absence of systematic screening were significant determinants of poor outcome, whereas treatment did not have significant influence.

A case of Candida haemulonii osteitis: clinical features, biochemical characteristics, and antifungal resistance profile.

We describe here the first case of osteitis caused by Candida haemulonii in a young immunocompetent patient. This patient presented a history of severe peripheral vascular disease associated with a lack of hygienic conditions as the only risk factors for such an uncommon infection. Clinical signs and histological examination allowed us to determine that it was a C. haemulonii infection and not colonization. The outcome was favourable with oral voriconazole therapy and surgical revascularization. An environmental cause of such infections is most probable, as C. haemulonii has previously been isolated from different non-human sources. Identification methods, results obtained with three in vitro antifungal susceptibility methods and clinical features are reported.

False-positive Aspergillus real-time PCR assay due to a nutritional supplement in a bone marrow transplant recipient with GVH disease.

PCR screening for circulating DNA, especially when combined with antigen testing, has shown promise for the definitive diagnosis of invasive aspergillosis. False positives for Aspergillus real-time PCR assays have been described in several reports, but no sources of fungal DNA contamination could be clearly identified. We report a false-positive case for both galactomannan (GM) antigenemia and Aspergillus PCR due to nutritional supplement intake in a bone marrow transplant recipient with digestive graft-versus-host disease. Our case report also suggests that fungal DNA can pass into the serum from the intestinal tract in the same way as fungal GM. Clinicians should be aware of this possibility, so that the administration of costly, unnecessary antifungal treatments with potential adverse side-effects can be avoided.

Personalized management of patients with inoperable alveolar echinococcosis undergoing treatment with albendazole: usefulness of positron-emission-tomography combined with serological and computed tomography follow-up.

The present study aimed to identify a sub-group of inoperable alveolar echinococcosis (AE) patients undergoing long-term treatment with benzimidazole (BZM) who presented with an evolution suggestive of a parasitocidal effect. An evolution compatible with parasite death was observed in five patients.

Evaluation of a new gridding method for fully 3D direct Fourier PET reconstruction based on a two-plane geometry.

This study investigated how the choice of fixed planes for the representation of the projection data of a cylindrical positron emission tomography (PET) scanner simplifies the frequency interpolation required by the 3D Fourier slice theorem (3D-FST). A new gridding algorithm based on a two-plane geometry and requiring only 1D interpolations in the Fourier domain was compared with the direct implementation of the 3D-FST. We show that the use of two orthogonal planes leads to signal to noise ratios similar to those achieved with the 3D-FST algorithm from projection data acquired with up to two times more count rates, while the resolution remains similar.

Control of the duration of urinary catheterization: impact on catheter-associated urinary tract infection.

Catheter-associated urinary tract infection (CAUTI) is one of the most common types of nosocomial infection. Reducing the duration of catheterization may be a key intervention in CAUTI prevention. We carried out a prospective time-sequence, non-randomized intervention study in five departments of our university hospital. We wished to determine the impact of daily reminders from nurses to physicians to remove unnecessary urinary catheters four days after insertion. The intervention significantly decreased the duration of catheterization in two out of five departments. The frequency of late CAUTI (LCAUTI) among catheterized patients in all five departments decreased from 10.6 to 1.1 per 100 patients (P = 0.003) and the incidence of LCAUTI decreased from 12.3 to 1.8 per 1000 catheter-days (P = 0.03). Logistic regression analysis showed that duration of catheterization and iterative catheter changes were associated with LCAUTI. This study demonstrates that a simple measure can reduce the frequency of LCAUTI.

Changes of volatile compounds during heating of bacuri pulp.

The formation of volatile compounds from precursors or through chemical rearrangement during heat treatment of bacuri pulp at fruit natural pH were studied using simultaneous distillation/extraction (SDE) technique. An increase of the quantities of oxygenated and hydrocarbon terpenes and, to a lesser degree, aldehydes, was observed after SDE at pH 3, relative to the other extraction methods used, SDE at neutral pH and solid phase extraction (SPE). More particularly, linalool, linalool furanoxides, alpha-terpineol, hotrienol, nerol oxide, nerol, and geraniol were isolated in more important quantities after the first treatment than after the others. These results can be partially explained by the hydrolysis of glycosidically bound compounds previously identified in bacuri. Other pathways such as polyol rearrangements were also involved. The formation of linalool and alpha-terpineol was probably the result of the rearrangement of 2,6-dimethyloct-1-ene-3,7-diol. Moreover, it was assumed that oxidation reactions occurred during SDE at pH 3; more particularly, linalool pyranoxides partially resulted from nonenzymatic oxidation of linalool. When SDE was performed at pH 3, an increase of furfural and 4-methoxy-2,5-dimethyl-3(2H)-furanone was noticed. The modifications of the concentration of aliphatic aldehydes, known as lipid oxidation compounds, and of fatty acid esters were in good agreement with the observed decrease of palmitic and linoleic acid concentrations during this treatment. Moreover, important amounts of 2-acetyl-1-pyrroline were found in the SDE extract recovered at pH 7.

Aroma compounds-proteins interaction using headspace techniques.

Interactions between volatile compounds and proteins in aqueous solution, were studied using static and dynamic headspace techniques. The decrease of aroma compounds concentration in the headspace determined in static mode indicates a retention by beta-lactoglobulin, 2.4% (w/w), pH 3.4, 25 degrees C, varying from 8 to 60% for most of the compounds tested. However 2-hexanone and isoamyl acetate are not significantly retained by the protein and a salting-out effect is noticed for limonene. On the basis of these preliminary results the intensity of interactions of methyl ketones (C7 to C9), ethyl esters (C6 to C9), limonene and mgamma rcene and beta-lactoglobulin for different pH values (2.0 to 11.0) were estimated by the determination of the infinite dilution activity coefficients (gamma i) by exponential dilution. For a constant pH value, the relative activity coefficient in the presence of beta-lactoglobulin (gamma r) of methyl ketones decreases significantly with the hydrophobicity of the volatiles whereas the relative activity coefficient value reaches a minimum for ethyl octanoate in the ester series. For limonene and myrcene an increase of gamma r is generally noticed whereas a decrease occurs in the presence of sodium caseinate and bovine serum albumin. The variations of relative activity coefficient according to the pH of the medium can be related to structural modifications of the beta-lactoglobulin.

Degenerated pIX-IVa2 adenoviral vector sequences lowers reacquisition of the E1 genes during virus amplification in 293 cells.

A critical issue for E1-deleted adenoviral vectors manufactured from 293 cells is the emergence of replication-competent adenovirus (RCA). These contaminants arise through homologous recombination between identical sequences framing the E1 locus displayed by 293 cells, and the vector backbones. Modified recombinogenic sequences (syngen) were thus introduced within the vector backbone, and virus viability and RCA emergence were assessed. Syngen#1 is a synthetic sequence displaying silent point mutations in the pIX and IVa2 coding regions. A side by side comparison of Ad5CMV/p53 (E1-deleted adenovirus expressing the p53 tumor suppressor gene) and AVdeltaE1#1CMV/p53 (with syngen#1 in place of wild-type sequences) demonstrated a normal productivity for the modified construct. The altered sequences did not impair p53-mediated apoptosis in a model tumor cell line. Most importantly, a statistically significant decrease in terms of RCA occurrence could also be demonstrated. Degenerescence of the recombinogenic sequences could be further accentuated by modifying noncoding pIX region (syngen #2), with no effect on virus productivity and stability. We concluded that these vector modifications constitute a feasible strategy to reduce RCA emergence during amplification in 293 cells. This approach could also be applied to decrease reincorporation of the E1 genes during amplification of deltaE1deltaE4 vectors in 293/E4-trans-complementing cells.

Determination of apparent binding constants for aroma compounds with beta-lactoglobulin by dynamic coupled column liquid chromatography.

Apparent binding constants of aroma compounds limonene, alpha- and beta-ionone, and terpenyl acetate, with beta-lactoglobulin (BLG), were determined, using dynamic coupled column liquid chromatography, for pH values varying from 3 to 11. K(a) values varied from 2.61 to 3.21 x 10(3) M(-1) for limonene, indicating a strong interaction with BLG. Similarly, significant and close apparent binding constants were obtained for alpha- and beta-ionone, 1.7 x 10(2) and 4.5 to 5.4 x 10(2) M(-1), respectively. These data indicated that a similar mechanism is involved for the binding of these two molecules. The weaker values obtained at low pH, for alpha-ionone relative to beta-ionone, can be explained by the existence of steric hindrance. An increase of the apparent binding constant was observed, for all the compounds studied, when the pH was increased from 3 to 9. At this pH, an apparent binding constant was obtained for terpenyl acetate (1.04 x 10(2) M(-1)), whereas this determination was not possible at pH 3 and 6. The apparent binding constant increase was in agreement with the decrease of aroma compound relative activity coefficient in the presence of BLG, previously observed at this pH. It indicated a best accessibility to the same binding site. The binding constants of all the aroma compounds studied decreased at pH 11 as a result of the important release of the BLG structure previously reported.

Osteoporotic fractures at presentation of Cushing's disease: two case reports and a literature review.

Osteoporosis is a common complication of Cushing's disease/syndrome. Fractures can be the presenting manifestation. We report two cases and review 28 others from the literature. Clinical, laboratory, and absorptiometry data are reviewed; the vertebrae and ribs were the most common fracture sites, and osteoporosis reversal after treatment varied with age, gender, and symptom duration. The pathophysiology, which remains controversial, is discussed. A search for Cushing's disease/syndrome should be part of the routine evaluation of osteoporosis in children and adults, particularly men.

Effect of pH on retention of aroma compounds by beta-lactoglobulin.

Interactions between volatile compounds and BLG in aqueous solution were studied using static and dynamic headspace techniques (exponential dilution). The intensity of interactions between methyl ketones (C7-C9), ethyl esters (C6-C9), limonene, myrcene, and beta-lactoglobulin (BLG) were estimated by determination of the relative infinite dilution activity coefficients (gamma(r)). For a constant pH value, the methyl ketones retention by BLG increased significantly with the hydrophobicity of the volatiles, whereas the retention reached a maximum for ethyl octanoate in the ester series, indicating a possible steric hindrance. For limonene and myrcene an unexpected increase in headspace concentration or "salting out" effect was noticed for acid pH. The variations of the retention according to the pH increase of the medium from pH 3 to pH 11 could be related to structural modifications of the BLG. The retention increase observed between pH 3 and pH 9 resulted from the flexibility modification of the protein, allowing better accessibility to the primary or the secondary hydrophobic sites, whereas the dramatic decrease observed at pH 11 was the consequence of the alkaline denaturation of BLG. Electrostatic interactions occurring at pH 7.5 could also explain the observed retention increase.

pCOR: a new design of plasmid vectors for nonviral gene therapy.

A totally redesigned host/vector system with improved properties in terms of safety has been developed. The pCOR plasmids are narrow-host range plasmid vectors for nonviral gene therapy. These plasmids contain a conditional origin of replication and must be propagated in a specifically engineered E. coli host strain, greatly reducing the potential for propagation in the environment or in treated patients. The pCOR backbone has several features that increase safety in terms of dissemination and selection: (1) the origin of replication requires a plasmid-specific initiator protein, pi protein, encoded by the pir gene limiting its host range to bacterial strains that produce this trans-acting protein; (2) the plasmid's selectable marker is not an antibiotic resistance gene but a gene encoding a bacterial suppressor tRNA. Optimized E. coli hosts supporting pCOR replication and selection were constructed. High yields of supercoiled pCOR monomers were obtained (100 mg/l) through fed-batch fermentation. pCOR vectors carrying the luciferase reporter gene gave high levels of luciferase activity when injected into murine skeletal muscle.

Spinal tuberculosis in adults. A study of 103 cases in a developed country, 1980-1994.

Spinal tuberculosis (TB) accounts for about 2% of all cases of TB. New methods of diagnosis such as magnetic resonance imaging (MRI) or percutaneous needle biopsy have emerged. Two distinct patterns of spinal TB can be identified, the classic form, called spondylodiscitis (SPD) in this article, and an increasingly common atypical form characterized by spondylitis without disk involvement (SPwD). We conducted a retrospective study of patients with spinal TB managed in the area of Paris, France, between 1980 and 1994 with the goal of defining the characteristics of spinal TB and comparing SPD to SPwD. The 103 consecutive patients included in our study had TB confirmed by bacteriologic and/or histologic studies of specimens from spinal or paraspinal lesions (93 patients) or from extraspinal skeletal lesions (10 patients). Sixty-eight percent of patients were foreign-born subjects from developing countries. None of our patients was HIV-positive. SPD accounted for 48% of cases and SPwD for 52%. Patients with SPwD were younger and more likely to be foreign-born and to have multiple skeletal TB lesions. Neurologic manifestations were observed in 50% of patients, with no differences between the SPD and SPwD groups. Of the 44 patients investigated by MRI, 6 had normal plain radiographs; MRI was consistently positive and demonstrated epidural involvement in 77% of cases. Bacteriologic and histologic yields were similar for surgical biopsy (n = 16) and for percutaneous needle aspiration and/or biopsy (n = 77). Cultures for Mycobacterium tuberculosis were positive in 83% of patients, and no strains were resistant to rifampin. Median duration of antituberculous chemotherapy was 14 months. Surgical treatment was performed in 24% of patients. There were 2 TB-related deaths. Our data suggest that SPwD may now be the most common pattern of spinal TB in foreign-born subjects in industrialized countries. The reasons for this remain to be elucidated.