Epidemiology and Investigations for Suspected Endometrial Cancer

ObjectiveTo review the evidence relating to the epidemiology of endometrial cancer and its diagnostic workups.OptionsWomen with possible endometrial cancer can undergo an endometrial evaluation by office biopsy, hysteroscopy, or dilatation and curettage. To assist in treatment planning, pelvic ultrasound, CT scan, or MRI may be considered.OutcomesThe identification of optimal diagnostic tests to evaluate patients with possible endometrial cancer.EvidencePublished literature was retrieved through searches of PubMed, CINAHL, and The Cochrane Library, using appropriate controlled vocabulary (e.g., endometrial neoplasms) and key words (e.g., endometrium cancer, endometrial carcinoma). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to December 31, 2011. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, national and international medical specialty societies, and recent conference abstracts.ValuesThe quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table).Benefits, harms, and costsThis document is intended to guide the development of a standardized cost-effective investigation of patients with suspected endometrial cancer.ValidationThe guideline was reviewed for accuracy by experts in pathology, radiation oncology, and medical oncology. Guideline content was also compared with relevant documents from the American Congress of Obstetricians and Gynecologists.     

Moderators of the intention-behaviour and perceived behavioural control-behaviour relationships for leisure-time physical activity

Background  

Intention is a key determinant of action. However, there is a gap between intention and behavioural performance that remains to be explained. Therefore, the aim of this study was to identify moderators of the intention-behaviour and perceived behavioural control (PBC)- behaviour relationships for leisure-time physical activity.     

The functional basis for hemophagocytic lymphohistiocytosis in a patient with co-inherited missense mutations in the perforin (PFN1) gene

About 30% of cases of the autosomal recessive immunodeficiency disorder hemophagocytic lymphohistiocytosis are believed to be caused by inactivating mutations of the perforin gene. We expressed perforin in rat basophil leukemia cells to define the basis of perforin dysfunction associated with two mutations, R225W and G429E, inherited by a compound heterozygote patient. Whereas RBL cells expressing wild-type perforin (67 kD) efficiently killed Jurkat target cells to which they were conjugated, the substitution to tryptophan at position 225 resulted in expression of a truncated ( approximately 45 kD) form of the protein, complete loss of cytotoxicity, and failure to traffic to rat basophil leukemia secretory granules. By contrast, G429E perforin was correctly processed, stored, and released, but the rat basophil leukemia cells possessed reduced cytotoxicity. The defective function of G429E perforin mapped downstream of exocytosis and was due to its reduced ability to bind lipid membranes in a calcium-dependent manner. This study elucidates the cellular basis for perforin dysfunctions in hemophagocytic lymphohistiocytosis and provides the means for studying structure-function relationships for lymphocyte perforin.     

Reliability of mini-bronchoalveolar lavage for the measurement of epithelial lining fluid concentrations of tobramycin in critically ill patients

Objective To evaluate the reliability of mini-bronchoalveolar lavage (mini-BAL) for the measurement of tobramycin concentrations in epithelial lining fluid (ELF) in comparison with conventional bronchoscopic bronchoalveolar lavage (BAL). Design Prospective, open-label study. Setting An intensive care unit and research ward in a university hospital. Patients Twelve critically ill adult patients with ventilator-associated pneumonia (VAP). Interventions All subjects received intravenous infusions of tobramycin 7–10 mg/kg once daily. After 2 days of therapy, the steady-state serum and ELF concentrations (obtained from BAL and mini-BAL) of tobramycin were determined by means of high-performance liquid chromatography. Measurements and results We observed poor penetration of tobramycin in ELF of ≈ 12% with ELF peak concentrations of ≈ 3 mg/l with both methods. Good agreement in Bland–Altman analysis (mean ± SD bias = 0.04 ± 0.38 mg/l) was observed between the two methods of sampling. Conclusion Our results suggest that tobramycin 7–10 mg/kg once daily in critically ill patients with VAP might provide insufficient lung concentrations in the case of difficult-to-treat pathogens. Besides, mini-BAL, which is simple, non-invasive and easily repeatable at the bedside, appears to be a reliable method for the measurement of antibiotic concentrations in ELF in comparison with bronchoscopic BAL in critically ill patients with VAP. This article is discussed in the editorial available at: . Support was provided only by institutional sources.     

Reproducibility of protected specimen brush and bronchoalveolar lavage conserved at 4 degrees C for 48 hours

OBJECTIVE: Protected specimen brush (PSB) and bronchoalveolar lavage (BAL) are proposed in combination to optimize antimicrobial treatment. Nevertheless, they are only validated for immediate laboratory processing. This study was therefore conducted to determine whether 48 h conservation at a mere 4 degrees C enables good culture reproducibility for both PSB and BAL. DESIGN AND SETTING: Prospective study, evaluation of a conservation procedure for PSB and BAL, from February 1994 to February 1995, in the 12 bed ICU of a general hospital (938 beds). SAMPLES: Ninety-nine PSB and 86 BAL samples, obtained from 100 bronchoscopic procedures, were analyzed. Thresholds were 10(3) and 10(4) cfu/ml for PSB and BAL, respectively. MEASUREMENTS AND RESULTS: Qualitative comparison between the immediate and 48 h procedures were, for PSB, specificity 100%, sensitivity 78%, positive predictive value 100%, negative predictive value 84% and overall accuracy 90%; and for BAL: 100%, 89%, 100%, 89% and 94%. Lowered 10(2) and 10(3) cfu/ml thresholds at the 48 h procedure for PSB and BAL reduce the false negatives from 10 to 3 and 5 to 1, respectively. Microorganism results were comparable for PSB and BAL ( r = 0.63 and 0.67), especially for the most resistant strains: Staphylococcus, Enterobacteriaceae and Pseudomonas. However, there was a decrease in the Neisseria and Haemophilus group ( p < 0.01). CONCLUSION: There is a good culture reproducibility for both PSB and BAL after 48 h conservation at 4 degrees C, especially with lowered thresholds; this technique is therefore appropriate for routine use.     

Steady-state plasma and intrapulmonary concentrations of piperacillin/tazobactam 4 g/0.5 g administered to critically ill patients with severe nosocomial pneumonia

Objective To determine the steady-state plasma and epithelial lining fluid (ELF) concentrations of piperacillin/tazobactam (P/T) administered to critically ill patients with severe bacterial pneumonia.Design Prospective, open-label study.Setting An intensive care unit and research ward in a university hospital.Patients Ten adult patients with severe nosocomial bacterial pneumonia on mechanical ventilation.Interventions All subjects received a 30-min intravenous infusion of P/T 4 g/0.5 g every 8 h. The steady-state plasma and ELF concentrations of P/T were determined by high-performance liquid chromatography.Measurements and main results The mean±SD steady-state plasma trough, peak, and intermediate concentrations were 8.5±4.6 µg/ml, 55.9±21.6 µg/ml, and 24.0±13.8 µg/ml for piperacillin, and 2.1±1.0 µg/ml, 4.8±2.1 µg/ml, and 2.4±1.2 µg/ml for tazobactam, respectively. The mean±SD steady-state intermediate ELF concentrations were 13.6±9.4 µg/ml for piperacillin and 2.1±1.1 µg/ml for tazobactam, respectively, showing a mean percentage penetration of piperacillin and tazobactam into ELF of 56.8% and 91.3 %, respectively, with a P/T ratio of 6.5:1.Conclusion Our results show that during the treatment of severe nosocomial pneumonia, a regimen of P/T 4 g/0.5 g every 8 h might provide insufficient concentrations into lung tissue to exceed the MIC of many causative pathogens. This suggests that higher doses of P/T should be administered in order to maximize the antibiotic concentration at the site of infection, or that a second antimicrobial agent should be used in association.