Synthesis and biological studies of iodinated (127/125I) derivatives of rhodamine 123

Rhodamine 123, a mitochondrial stain that preferentially accumulates in certain cancer cells, has been reduced and iodinated by using NaI in the presence of N-chlorosuccinimide. The various mono-, di-, and triiodo derivatives have been isolated and characterized. These nonfluorescent compounds are taken up by mammalian cells, become fluorescent within the cytoplasm (presumably following oxidation), and show the same pattern of localization as the parent compound. Iodination with no-carrier-added Na125I yields the same mixture of compounds. All 125I derivatives accumulate preferentially in PC3 adenocarcinoma cells compared with V79 lung fibroblasts, with the differential being greatest for the monoiodo compound, followed by the di- and triiodo derivatives.     

Factors predicting ventilator-associated pneumonia recurrence

OBJECTIVE: To determine the factors associated with ventilator-associated pneumonia recurrence in patients alive after 8 days of treatment for a first episode. DESIGN: A 16-month, prospective, observational cohort study of patients diagnosed with a first ventilator-associated pneumonia episode. Predictors of recurrence were assessed by logistic regression analysis. SETTING: Two intensive care units in a university hospital. PATIENTS: Bronchoscopy was performed in 124 patients with clinically or radiologically suspected ventilator-associated pneumonia. Ventilator-associated pneumonia was confirmed by the presence of at least two of the following criteria: >/=2% of cells with intracellular bacteria found on direct examination of bronchoalveolar lavage fluid, protected specimen brush sample culture >/=103 colony-forming units/mL, or bronchoalveolar lavage culture >/=104 colony-forming units/mL. Ventilator-associated pneumonia recurrence was confirmed using the same microbiological criteria. Antibiotic treatment for ventilator-associated pneumonia lasted 14 days. MEASUREMENTS AND MAIN RESULTS: Clinical, radiologic, and biological data at intensive care unit admission, on the day of bronchoscopy (D1) and on D8, and outcome variables were prospectively recorded. Ventilator-associated pneumonia recurred in 28 patients (all of them still on mechanical ventilation on D8), 21 +/- 9 days after the first episode (82% after D14). Factors significantly associated with recurrence were: acute respiratory failure as initial reason for mechanical ventilation, D1 radiologic score >7, D8 radiologic score >8, adult respiratory distress syndrome on D8, mechanical ventilation persistence on D8, D8 temperature >38 degrees C, and D8 temperature >D1 temperature, but not disease-severity scores at inclusion and D8, or first-episode pathogen(s). Multivariate analysis identified D1 radiologic score >7 (odds ratio = 3.9; 95% confidence interval, 1.3-11.6), D8 temperature >38 degrees C (odds ratio = 4.4; 95% confidence interval, 1.4-13.4), and adult respiratory distress syndrome on D8 (odds ratio = 14.6; 95% confidence interval, 1.5-143.5) as predictors of recurrence. CONCLUSIONS: Factors of ventilator-associated pneumonia recurrence evaluated on D8 of a 14-day course of antibiotics are linked to the severity of lung injury and persistence of fever, but not to first-episode pathogen(s).     

Sulodexide in Patients with Chronic Venous Disease of the Lower Limbs: Clinical Efficacy and Impact on Quality of Life

Introduction

Chronic venous disease (CVD) of the lower limbs is a common problem. It is more prevalent in women than in men and has a significant impact on patients’ quality of life (QoL) and on the healthcare system. The aim of this study was to evaluate the efficacy of sulodexide in adult patients with CVD of the lower limbs and its effect on patients’ QoL.

Methods

Patients with CVD were treated with sulodexide [250 LSU (lipasemic units) twice daily] for 3 months in a setting of real-life clinical practice. The endpoints of this observational non-comparative, open-label prospective study were the clinical efficacy of sulodexide (evaluated by scoring objective and subjective symptoms with a Likert-type scale) and the impact of sulodexide therapy on patients’ QoL [assessed using the chronic venous insufficiency quality of life questionnaire (CIVIQ)].

Results

The study included 450 patients (mean age 46.9 ± 10.5 years, range 17–78 years). A greater percentage of patients were female (65.4%). Three months of treatment with sulodexide significantly improved all objective and subjective symptoms (p < 0.0001). Overall, patients reported a significant improvement in all QoL scores (p < 0.0001). Adverse events were spontaneously reported by two patients (one case of epigastric pain and one of gastric pain with vomiting).

Conclusion

Oral sulodexide significantly improves both objective and subjective symptoms, as well as functional and psychological aspects of QoL in patients with CVD.

Funding

No funding or sponsorship was received for this study. Sponsorship for article processing charges and open access fees was provided by Alfa Wassermann.

     

Lack of effect of sugar cane policosanol on plasma cholesterol in Golden Syrian hamsters

Policosanol is a mixture of higher aliphatic alcohols shown to have beneficial effects on plasma lipid levels in animals and humans. Over 50 studies have reported significant reductions in plasma cholesterol using policosanol obtained from Cuban sugar cane (Dalmer, La Havana, Cuba). However, other research groups using policosanol from alternative sources have failed to reproduce the efficacy of these alcohols observed in earlier studies. Therefore, the objective of the present study was to compare the cholesterol-lowering effect of the Dalmer sugar cane policosanol (SCP) product versus an alternative mixture of similar policosanol composition. Forty-eight male Golden Syrian hamsters were randomly assigned to four groups and fed experimental diets ad libitum for a period of 4 weeks: (i) non-cholesterol control, (ii) 0.1% cholesterol control, (iii) 0.1% cholesterol diet supplemented with 275 mg/kg diet of Dalmer Cuban sugar cane policosanol and (iv) 0.1% cholesterol diet supplemented with 275 mg/kg diet of alternative sugar cane policosanol. Hamsters were sacrificed and blood was collected at the end of the feeding period. Body weights and food intakes were similar across study groups. Neither of the two policosanol treatments had any significant effect on plasma lipid levels, as compared to cholesterol control. The outcome of the present study questions the clinical usefulness of policosanol mixtures as cholesterol-lowering nutraceuticals.     

Differentiating Culture Samples Representing Coagulase-Negative Staphylococcal Bacteremia from Those Representing Contamination by Use of Time-to-Positivity and Quantitative Blood Culture Methods

Differentiating true coagulase-negative staphylococcal infection from contamination has an important impact on therapeutic implications. Time to positivity reflects bacterial density and may help in the interpretation of blood cultures. We retrospectively reviewed the records of 272 patients from June 2005 to January 2008 for clinical characteristics, microbiological data, and therapeutic outcome. Four groups were identified. The first three groups, as follows, included patients with one positive quantitative blood culture: the low-colony-count group (<10 CFU/ml), the moderate-colony-count group (30 to 100 CFU/ml), and the high-colony-count group (>100 CFU/ml). The control group included patients with two positive quantitative blood cultures and definite coagulase-negative staphylococcal bloodstream infection. The high-colony-count group had shorter time to positivity (≤16 h) than did the low-colony-count group (P < 0.0001). The low-colony-count group had a significantly longer time to positivity, >20 h (P = 0.001), than did the moderate-colony-count group. Even though antibiotics were not provided in 71% of cases and central venous catheter was retained in 83%, the low-colony-count group had a favorable outcome, suggesting that <10 CFU/ml represents contamination. The high-colony-count group, similar to the positive control group, required antibiotics in 81% of cases and central venous catheter removal in 51% (P = 0.001). A time to positivity of ≤16 h reflects high-grade bacteremia with CFU of >100. Similar to the positive control group, these patients required an active therapeutic approach. A time to positivity of >20 h indicates possible contamination with a CFU of <10, and active therapy may not be required.Coagulase-negative staphylococci (CoNS) are the most commonly isolated contaminants from blood cultures, yet they are the most frequent cause of true bloodstream infections (9). This distinction has practical importance because of its therapeutic implications in terms of unnecessary use of antibiotics and emergence of resistance (6). Furthermore, failure to recognize and treat true bacteremia can lead to higher rates of morbidity and mortality, especially in the critically ill or immunocompromised cancer patients (15). Interpretation of the significance of CoNS-positive blood cultures is aided by the number of positive cultures, but this assessment is difficult when only a single culture sample is obtained before the initiation of antibiotic therapy (10). Quantitative blood cultures (QBCs) can aid interpretation but are not widely available in most laboratories. On the other hand, the time-to-positivity (TP) method has been suggested as a surrogate test for bacterial density and may also help in the interpretation of positive blood cultures, as QBCs do (1).We postulated that patients with QBCs positive for a low colony count correlate with a prolonged TP and may reflect CoNS contamination. As a consequence, those patients require no therapeutic approach, whereas patients with QBCs positive for a high colony count correlate with a shorter TP and may reflect true CoNS bacteremia. Those patients require adequate therapeutic approach to achieve clinical and microbiologic resolution.     

Direct medical mental health care costs of schizophrenia in France,Germany and the United Kingdom – Findings from the European Schizophrenia Cohort (EuroSC)

ObjectivesTo quantify and compare the resource consumption and direct costs of medical mental health care of patients suffering from schizophrenia in France, Germany and the United Kingdom.MethodsIn the European Cohort Study of Schizophrenia, a naturalistic two-year follow-up study, patients were recruited in France (N = 288), Germany (N = 618), and the United Kingdom (N = 302). Data about the use of services and medication were collected. Unit cost data were obtained and transformed into United States Dollar Purchasing Power Parities (USD-PPP). Mean service use and costs were estimated using between-effects regression models.ResultsIn the French/German/UK sample estimated means for a six-month period were respectively 5.7, 7.5 and 6.4 inpatient days, and 11.0, 1.3, and 0.7 day-clinic days. After controlling for age, sex, number of former hospitalizations and psychopathology (CGI score), mean costs were 3700/2815/3352 USD-PPP.ConclusionsService use and estimated costs varied considerably between countries. The greatest differences were related to day-clinic use. The use of services was not consistently higher in one country than in the others. Estimated costs did not necessarily reflect the quantity of service use, since unit costs for individual types of service varied considerably between countries.