Growth factor expression after supraspinatus tear: a quantitative polymerase chain reaction (PCR) study in rats.

INTRODUCTION: The objective of this study was to evaluate the temporal expression pattern of three different growth factors (VEGF, IL-1ß, and TGF-1ß) in a supraspinatus tendon lesion in an animal model. The hypothesis of this study is that there are variations in the expression of these factors in the first 8 weeks after injury. MATERIALS AND METHODS: A full thickness defect was made in the supraspinatus tendon of 40 rat shoulders. The animal were sacrificed at 0, 3, 7, 14 and 56 days after injury and three tissue samples were obtained: bone from the tendon footprint; the supraspinatus tendon stump, and a fragment of the myotendinous junction. After mRNA extraction, quantitative PCR analysis was performed, and the expression of three different growth factors were evaluated in each zone. RESULTS: There was an increased expression of IL-1ß during the first week after injury at all levels evaluated with a clear peak in the first day after injury. There was also a significant increase in TGF-1ß expression levels all along the first week in the three zones. There were no variations in VEGF expression in the three zones along the 8 weeks. CONCLUSION: IL-1ß was expressed predominantly in the initial stages after injury; TGF initiated its expression after the initial phase since day three, whereas VEGF remained basically unchanged during the entire process.

[Spanish multicentre study for the prevention of medication errors: results over four years (2007-2011)]. / Estudio Multicéntrico español para la Prevención de Errores de Medicación. Resultados de cuatro años (2007-2011).

OBJECTIVE: The primary objective of the Spanish Multicentre Study for the Prevention of Medication Errors 2007-2011 was to increase patient safety by improving drug practices in 26 participating Spanish hospitals. The secondary objective was to ascertain the medication error rate. METHOD: We used a modified Barker and McConnell observation method. RESULTS: During 2007-2008, 21 009 observations were recorded In 23 hospitals; during 2008-2009, 11 320 observations were recorded in 10 hospitals; during 2009-2010, 6819 observations were recorded in 8 hospitals, and during 2010-2011, 5876 observations were recorded in six hospitals. Error rates, including medication time errors and failure to inform patients came to 21.7%, 33.3%, 35.6% and 25.7% in each of the years respectively. Excluding time errors, the rates were 18.2%, 32.2%, 33.4% and 23.5%; excluding failure to inform patients as well, rates dropped to 12.6%, 14.8%, 12.8% and 8.6%. STRATEGIES FOR IMPROVEMENT: a normalised drug administration timetable, normalised IV drug dilutions and rates, better drug administration coordination with mealtimes, electronic prescription, improved patient identification measures, adjusting doses for kidney function, drug reconciliation programmes and patient and drug bar code scanning. CONCLUSIONS: 1. The applied measures improved patient safety through better drug practices in participating EMOPEM hospitals. 2. Drug error rates obtained for this sample of Spanish hospitals are some of the highest published. They are significantly lower, however, when we exclude time errors and failure to inform the patient.

Personality traits in early phases of panic disorder: implications on the presence of agoraphobia, clinical severity and short-term outcome.

OBJECTIVE: To explore the relations between personality traits using the Big Five model and presence of agoraphobia, clinical severity and short-term outcome in an unbiased clinical sample of never-treated panic disorder patients. METHOD: Panic disorder (PD) patients (n = 103) in the first stages of their illness were evaluated using the Neuroticism-Extraversion-Openness Five Factor Inventory of Personality (NEO-FFI) and were compared with a sample of healthy subjects. Severity was assessed by the Panic Disorder Severity Scale and the Clinical Global Impression Scales. Patients were evaluated after 8 weeks of naturalistic pharmacologic treatment with Selective Serotonin Reuptake Inhibitors. RESULTS: Panic disorder patients show more neuroticism than healthy subjects. Patients suffering from agoraphobia are more introverted than controls. Extraversion, in addition to gender and distress, during panic attacks allows to correctly classifying 72% of the cases of agoraphobia. CONCLUSION: Low scores in extraversion contribute to explain the presence of agoraphobia in panic disorder. Personality traits are neither related to clinical severity nor to short-term response to pharmacological treatment.

Stability of amphotericin B in an extemporaneously prepared i.v. fat emulsion.

The stability of amphotericin B in an extemporaneously prepared i.v. fat emulsion was studied. Admixtures of amphotericin B 0.5, 1, and 2 mg/mL were prepared by adding 10, 20, and 40 mL of amphotericin B 5 mg/mL to 90, 80, and 60 mL, respectively, of 20% fat emulsion. The admixtures were stored in glass vacuum containers at 20-25 degrees C and exposed to fluorescent light, 20-25 degrees C and protected from light, or 4-8 degrees C and protected from light. A sample was withdrawn from each container at 0, 4, 12, and 24 hours and at 2, 4, 7, and 15 days for analysis of amphotericin B concentration by high-performance liquid chromatography and for visual evaluations; these samples were immediately frozen until analyzed. A sample was withdrawn from one container of amphotericin B 1 and 2 mg/mL for each storage condition at 0, 7, and 15 days for immediate determination of particle-size distribution with a fluorescinated-antibody cell sorter. Amphotericin B 0.5 mg/mL in 20% fat emulsion was stable for one week under all the storage conditions. Amphotericin B in the 1- and 2-mg/mL admixtures was stable for up to four days at 20-25 degrees C exposed to fluorescent light, and for up to one week at 20-25 degrees C protected from light and at 4-8 degrees C protected from light. There was no visible evidence of incompatibility. There were no substantial changes in particle-size distribution for the 1-mg/mL admixtures; appreciable changes were detected for the 2-mg/mL admixtures. Amphotericin B 1 and 2 mg/mL was stable in 20% fat emulsion for four days at 20-25 degrees C exposed to fluorescent light and for seven days at 20-25 degrees C protected from light or at 4-8 degrees C; amphotericin B 0.5 mg/mL was stable in 20% fat emulsion for seven days under the three storage conditions.

Pharmacokinetics of conventional formulation versus fat emulsion formulation of amphotericin B in a group of patients with neutropenia.

The pharmacokinetics of amphotericin B administered in a conventional 5% dextrose (glucose) (5% D) solution and in a 20% fat emulsion formulation (Intralipid; 20% IL) were compared in 16 patients (mean age, 42 years [range, 18 to 70 years]) who had been hospitalized for hematological malignancies and with proven or suspected fungal infections. All of the patients received 50 mg (approximately 1 mg/kg of body weight per day) of amphotericin B daily in random order, either as a 50-ml lipid emulsion (20% IL) (group I) or in 500 ml of 5% D (group II). Five serum samples were taken during the 24 h after drug administration, and the levels of amphotericin B were measured by high-pressure liquid chromatography. Serum amphotericin B concentrations declined rapidly during the first 6 h, and subsequent measurements revealed a slow terminal elimination phase in both groups. The maximum serum amphotericin B concentration was significantly lower when the drug was administered in 20% IL (1.46 +/- 0.61 versus 2.83 +/- 1.17 micrograms/ml; P = 0.02). The area under the concentration-time curve from 0 to 24 h was also much lower in group I (17.22 +/- 11.15 versus 28.98 +/- 15.46 micrograms.h/ml). The half-life of the distribution phase was approximately three times longer in group I (2.92 +/- 2.34 h versus 0.64 +/- 0.24 h; P = 0.011). Conversely, the half-lives of the elimination phase were approximately equal in the two groups (11.44 +/- 5.18 versus 15.23 +/- 5.25 h). The mean residence times were also similar in both groups (19.41 +/- 11.13 versus 19.65 +/- 7.86 h). The clearance and the steady-state volume of distribution of amphotericin B in group I were about twice as great as those in group II (62.97 +/- 35.51 versus 33.01 +/- 14.33 ml/kg/h and 1,043.92 +/- 512.10 versus 562.32 +/- 152.05 ml/kg [P = 0.034], respectively). Finally, the volume of distribution in the central compartment was greater in group I than in group II (618.17 +/- 231.80 versus 328.19 +/- 151.71 ml/kg; P = 0.013), but there were no differences in the volume of distribution in the peripheral compartment (425.75 +/- 352.87 versus 234.14 +/- 75.92 ml/kg). These results suggest that amphotericin B has a different pharmacokinetic profile when it is administered in 20% IL than when it is administered in the standard 5% D form and that the main difference is due to a clear-cut difference in the steady-state volume of distribution, especially that in the central compartment.

Administration of lipid-emulsion versus conventional amphotericin B in patients with neutropenia.

OBJECTIVE: To evaluate the usefulness of a 20% lipid emulsion as a delivery system for amphotericin B (1 mg/mL) administered over 1 hour to patients with neutropenia with hematologic malignancies compared with amphotericin B (0.1 mg/mL) administered in dextrose 5% solution over the same time. DESIGN: A prospective, comparative, randomized, labeled study. SETTING: Hematology unit, pharmacy service, university general hospital. PARTICIPANTS: Twenty patients with neutropenia with hematologic malignancies and proven or suspected fungal infections, 10 in the fat emulsion group (group 1) and 10 in the dextrose 5% group (group 2). MAIN OUTCOME MEASURES: Clinical tolerance (i.e., fever, shaking chills, nausea, blood pressure, pulse rate) and biologic tolerance (i.e., urea, creatinine, sodium, potassium). RESULTS: Clinical tolerance was comparable in both groups although amphotericin B in fat emulsion was better tolerated. Medication for symptoms related to the administration of amphotericin B was given in 6 cases in group 1 and in 8 cases in group 2. There was a statistically significant difference in the urea concentrations between the 2 groups (p = 0.023); there was an observed increase between the initial and the final serum urea (56.8 mg/d in group 1, 79.8 mg/dL in group 2). Statistically significant differences in creatinine serum concentrations (84.9 mumol/L in group 1, 123.8 mumol/L in group 2) (p = 0.047) were found. No differences were found in the antifungal efficacy of the treatment. However, as amphotericin B was started in the majority of cases (75%) as empiric treatment for fever unresponsive to antibiotic therapy, it is difficult to compare the efficacy of both preparations. CONCLUSIONS: The clinical tolerance of lipid-emulsion infusions is similar to that of conventionally administered amphotericin B therapy. Renal toxicity appears to be decreased when the drug is administered in a fat emulsion. This type of preparation permits the reduction of the volume and the time of administration for amphotericin B therapy.

An association between clotting factor concentrates use and mortality in human immunodeficiency virus-infected hemophilic patients.

There is much evidence that clotting factor concentrates (CFC), especially the so-called intermediate-purity preparations, exert an immunomodulating effect in vitro. The impact of this effect on the outcome of human immunodeficiency virus (HIV) infection in hemophiliacs is still controversial. In this retrospective cohort study, the effects of treatment with CFC on mortality and progression to acquired immunodeficiency syndrome (AIDS) were estimated while controlling for individual risk factors. Logistic regression and survival analysis, including the Cox proportional-hazards regression model, were performed with data from a 11-year follow-up of 225 hemophilic patients seropositive for HIV type 1 (HIV-1) of two hemophilia centers. Mortality and progression to AIDS rates were strongly associated with lower administration of CFC. After adjusting for age, a statistically significant and robust association was observed. The use of CFC was negatively associated with progression to AIDS (P = .0252) and mortality (P = .0033). The adjusted relative hazards of mortality and progression to AIDS rate between the most treated patients (> 700 IU/kg/yr) versus the least treated (< or = 700 IU/kg/yr) were 0.53 (confidence limits, 0.33 to 0.86) and 0.57 (0.39 to 0.84), respectively. Although the effects of other unmeasured risk factors cannot be excluded with certainty, these results suggest that there is a negative association between treatment with CFC and progression to AIDS and mortality.