Amphiphilic Antimony(V) Complexes for Oral Treatment of Visceral Leishmaniasis

The need for daily parenteral administration is an important limitation in the clinical use of pentavalent antimonial drugs against leishmaniasis. In this study, amphiphilic antimony(V) complexes were prepared from alkylmethylglucamides (L8 and L10, with carbon chain lengths of 8 and 10, respectively), and their potential for the oral treatment of visceral leishmaniasis (VL) was evaluated. Complexes of Sb and ligand at 1:3 (SbL8 and SbL10) were obtained from the reaction of antimony(V) with L8 and L10, as evidenced by elemental and electrospray ionization-tandem mass spectrometry (ESI-MS) analyses. Fluorescence probing of hydrophobic environment and negative-staining transmission electron microscopy showed that SbL8 forms kinetically stabilized nanoassemblies in water. Pharmacokinetic studies with mice in which the compound was administered by the oral route at 200 mg of Sb/kg of body weight indicated that the SbL8 complex promoted greater and more sustained Sb levels in serum and liver than the levels obtained for the conventional antimonial drug meglumine antimoniate (Glucantime [Glu]). The efficacy of SbL8 and SbL10 administered by the oral route was evaluated in BALB/c mice infected with Leishmania infantum after a daily dose of 200 mg of Sb/kg for 20 days. Both complexes promoted significant reduction in the liver and spleen parasite burdens in relation to those in the saline-treated control group. The extent of parasite suppression (>99.96%) was similar to that achieved after Glu given intraperitoneally at 80 mg of Sb/kg/day. As expected, there was no significant reduction in the parasitic load in the group treated orally with Glu at 200 mg of Sb/(kg day). In conclusion, amphiphilic antimony(V) complexes emerge as an innovative and promising strategy for the oral treatment of VL.     

Death and the preclinical medical student ii: Attitudes toward telling the terminal patient the prognosis

Abstract

The first and second year students in the Faculty of Medicine were surveyed concerning their attitudes toward informing a person that his or her illness was likely to be terminal if the person in question were the student, a parent, or a member of the general public. Attitudes were overwhelmingly in favor of direct truth telling, especially in the second year group. The possible influence of the first year course in Behavioral Sciences is considered.     

Recovery of Renal Function in Heart Transplantation Patients After Conversion From a Calcineurin Inhibitor-Based Therapy to Sirolimus

Background

Renal failure is the most important comorbidity in patients with heart transplantation, it is associated with increased mortality. The major cause of renal dysfunction is the toxic effects of calcineurin inhibitors (CNI). Sirolimus, a proliferation signal inhibitor, is an imunossupressant recently introduced in cardiac transplantation. Its nonnephrotoxic properties make it an attractive immunosuppressive agent for patients with renal dysfunction. In this study, we evaluated the improvement in renal function after switching the CNI to sirolimus among patients with new-onset kidney dysfunction after heart transplantation.

Methods

The study included orthotopic cardiac transplant (OHT) patients who required discontinuation of CNI due to worsening renal function (creatinine clearance < 50 mL/min). We excluded subjects who had another indication for initiation of sirolimus, that is, rejection, malignancy, or allograft vasculopathy. The patients were followed for 6 months. The creatinine clearance (CrCl) was estimated according to the Cockcroft-Gault equation using the baseline weight and the serum creatinine at the time of introduction of sirolimus and 6 months there after. Nine patients were included, 7 (78%) were males and the overall mean age was 60.1 ± 12.3 years and time since transplantation 8.7 ± 6.1 years. The allograft was beyond 1 year in all patients. There was a significant improvement in the serum creatinine (2.98 ± 0.9 to 1.69 ± 0.5 mg/dL, P = .01) and CrCl (24.9 ± 6.5 to 45.7 ± 17.2 mL/min, P = .005) at 6 months follow-up.

Conclusion

The replacement of CNI by sirolimus for imunosuppressive therapy for patients with renal failure after OHT was associated with a significant improvement in renal function after 6 months.     

Effect of Prophylactic Dalteparin on Anti-factor Xa Levels in Morbidly Obese Patients After Bariatric Surgery

Background

There are limited data on appropriate dosing of low-molecular-weight heparins (LMWH) for venous thromboembolism (VTE) prophylaxis in bariatric surgery. The objective of this study was to describe the postoperative effects of LMWH dalteparin on anti-factor Xa (AFXa) level in morbidly obese patients undergoing bariatric surgery.

Methods

This was a retrospective study. Morbidly obese patients (BMI?≥?40 kg/m² or BMI?>?35 kg/m² with at least one significant co-morbidity) received subcutaneous dalteparin 7,500 IU daily during the postoperative period after biliopancreatic derivation with duodenal switch. AFXa level was measured 4 h after the fourth dalteparin administration.

Results

One hundred and thirty-five patients with a mean BMI of 53.7 kg/m² were included into this study. Only 60% of patients had targeted AFXa levels (0.2–0.5 UI/ml). There was a statistical difference in body weight between individuals with sub-target AFXa levels and those with values over target (159.4?±?35.8 vs. 134.6?±?24.2, p?=?0.0310). There were three haemorrhages documented. These events were not associated with elevated AFXa values.

Conclusion

These findings indicate that the 7,500 IU dalteparin dosage is appropriate for the majority of morbidly obese patients undergoing bariatric surgery. The present study, however, suggests that this dose might not be sufficient for patient with a very high body weight.     

Incidence of Chest Tube Malposition in the Critically Ill: A Prospective Computed Tomography Study

Background: Malposition of percutaneously inserted chest tubes is considered as a rare complication in critically ill patients. Its incidence, however, remains uncertain. The aims of the study were to assess the true incidence of chest tube malposition in critically ill patients and to identify predicting factors.

Methods: The authors prospectively studied 122 chest tubes percutaneously inserted in 75 consecutive critically ill patients. For clinical reasons independent of the study, thoracic computed tomography scanning was performed in 63 patients, allowing direct visualization of 106 chest tubes. Based on these findings, chest tube position was classified as intrapleural, intrafissural, or intraparenchymal. Factors predicting chest tube malposition were analyzed by univariate and multivariate analysis.

Results: The mean delay between chest tube placement and thoracic scan was 3.5 +/- 2.9 days. Twenty-two chest tubes were diagnosed as being intrafissural (21%), and 10 were diagnosed as being intraparenchymal (9%). The only predicting factor associated with the risk of malposition was the use of a trocar for the percutaneous insertion of the chest tube (P = 0.032).     

High prevalence of self-reported depressive mood during the winter season among Swedish senior high school students

OBJECTIVE: There are few studies regarding the prevalence of seasonal variation in mood among children and adolescents. The main objective of this study was to estimate the prevalence of self-reported depressive mood during the winter season among Swedish adolescents and to investigate gender differences. Another aim was to analyze the factor structure and internal consistency of the Kiddie SPAQ (K-SPAQ), a pediatric version of the Seasonal Pattern Questionnaire (SPAQ). METHOD: All students 17 to 18 years old, registered in the second year of senior high school in Falun, a district in central Sweden, were screened with the K-SPAQ in January 2003 (response rate 87.3%, n = 756). RESULTS: The prevalence of self-reported depressive mood during the winter season was estimated at 20.1% (n = 151/751) and was higher among girls (25.5%) than boys (13.8%). Approximately 8% reported more severe depressive symptoms. Depressive mood during the summer was rare (0.1%, n = 1/751). Factor analysis of the General Seasonal Score items in the K-SPAQ revealed a two-factor structure. A Cronbach's alpha of 0.87 demonstrated a good internal consistency. CONCLUSIONS: Depressive symptoms during autumn and winter were common among Swedish senior high school students, especially among girls. This is probably an underdiagnosed condition among adolescents that ought to receive more attention from the health and school authorities.     

Role for interferon-gamma release assays in latent tuberculosis screening before TNF-α antagonist therapy

TNF-α antagonist therapy is associated with a risk of severe, extrapulmonary, disseminated tuberculosis, which is fatal in 10% of cases. The risk of tuberculosis is increased four-fold in patients on TNF-α antagonist therapy. The main risk factors are a history of untreated or inadequately treated primary tuberculosis, recent contact with a tuberculosis patient, and residence in or travel to a high-endemicity region. Infection surveillance agencies throughout the world have issued recommendations to ensure the detection and treatment of latent tuberculosis before TNF-α antagonist initiation. These recommendations have returned the incidence of tuberculosis to the level seen before the introduction of TNF-α antagonists. Nevertheless, there is still room for improvement. Recommendations about latent tuberculosis screening include the use of tuberculin skin tests. However, these tests are positive in individuals vaccinated with the BCG vaccine, which leads to overuse of tuberculosis chemoprophylaxis and, therefore, to unnecessary patient exposure to hepatotoxic effects. Furthermore, tuberculin skin tests may be falsely negative in immunosuppressed patients, leading to underuse of tuberculosis prophylaxis. These shortcomings of tuberculin skin tests have generated interest in interferon-gamma release assays (IGRAs). In patients with overt tuberculosis, IGRAs are more sensitive and more specific than tuberculin skin tests. However, the accuracy of IGRAs for diagnosing latent tuberculosis remains unknown, because no reference standard is available. In addition, patients taking immunosuppressant agents to treat systemic disease may exhibit anergia, which complicates the interpretation of IGRAs. Until additional data become available, caution requires that IGRAs be used only when a positive or negative result, as assessed on a case-by-case basis, will help to decide whether tuberculosis chemoprophylaxis is in order.     

Single-level anterior cervical discectomy and interbody fusion using PEEK anatomical cervical cage and allograft bone

Background  

In an effort to avoid the morbidity associated with autogenous bone graft harvesting, cervical cages in combination with allograft bone are used to achieve fusion. The goal of the current study was to assess the reliability and efficacy of anterior cervical discectomy and interbody fusion (ACDF) using a PEEK anatomical cervical cage in the treatment of patients affected by single-level cervical degenerative disease.