Prediction of moderate or severe pulmonary hypertension by main pulmonary artery diameter and main pulmonary artery diameter/ascending aorta diameter in pulmonary embolism

We investigated the accuracy of computed tomographic measurements of main pulmonary artery diameter (MPAD) and of MPAD/ascending aorta diameter (AAD) in predicting moderate or severe pulmonary hypertension in 190 patients with acute pulmonary embolism. A pulmonary artery systolic pressure of > or = 50 mm Hg measured by Doppler echocardiography was considered moderate or severe pulmonary hypertension. A MPAD of > 28.6 mm and a MPAD/AAD ratio of > or = 1.00 measured by computed tomography were considered abnormal. A MPAD of > 28.6 mm had a 75% sensitivity and specificity, a 52% positive predictive value, a 89% negative predictive value, a 3.0 likelihood ratio for a positive test, and a 0.33 likelihood ratio for a negative test in predicting moderate or severe pulmonary hypertension. A MPAD/AAD ratio of > or = 1.00 had a 59% sensitivity, a 82% specificity, a 55% positive predictive value, a 84% negative predictive value, a 3.3 likelihood ratio for a positive test, and a 0.50 likelihood ratio for a negative test.     

Antifibrotic effect of captopril and enalapril on paraquat-induced lung fibrosis in rats

Although different treatment modalities have been implemented for pulmonary fibrosis, the results have not been promising and these conditions have been considered untreatable and irreversible. Thus, a plethora of new drugs has been tried for the control of this condition in recent years. This study examined the effects of two angiotensin-converting enzyme inhibitors, captopril and enalapril, on paraquat-induced pulmonary fibrosis in rats, through biochemical and histopathological parameters. Male albino Wistar rats were divided into eight groups (n = 4-5 each), including control, paraquat, captopril alone, captopril treatment and pre-treatment, enalapril alone, enalapril treatment and pre-treatment. After 21 days of treatment, the lungs were removed and the levels of hydroxyproline, glutathione and lipid peroxidation were determined. Angiotensin-converting enzyme inhibitors showed no effect on glutathione and lipid peroxidation. The results also demonstrated that captopril and enalapril improved pulmonary fibrosis as shown by histopathology, as well as a decreased content of hydroxyproline (P < 0.001) in the lung tissue. In conclusion, the present findings suggest that the antifibrotic effect of these drugs may be related to the inhibition of angiotensin-converting enzyme.     

Pilot study for a new bipolar radiofrequency ablation/aspirator device in the management of primary and secondary liver cancers

Background: In the US, the thermal ablation workload for cancer involving the liver is predicted to more than double in the next 5 years, emphasising the need to develop and improve the current technology. Study Design: A multicentre nonrandomised prospective clinical trial (NCT00514930) was undertaken, to assess the efficacy and safety of a new bipolar radiofrequency ablation/aspirator device, in the treatment of primary and secondary cancers of the liver. Results: A total of 34 lesions in 16 patients were ablated at laparotomy and followed up at 4 weeks. The mean diameter of lesion before ablation was 3.2±2.22 (range 1–10) cm, the mean volume aspirated during ablation was 9.25±7.3 (range 0–25) ml and the mean operative time was 145.95±40.7 (range 60–215) min. There was one major complication of a pleural effusion, which required drainage. The mean length of stay was 8±3.2 (range 3–14) days. In 11 patients, the ablated tumour was resected. On histological assessment, there was no evidence of viable cancer at the tumour edge. On follow‐up computed tomography, the ablation zone fully encompassed the targeted tumour and there were no local complications related to ablation. Conclusion: Initial analysis of the data from this small cohort, with only a short‐term follow‐up, shows this device to be safe and effective.     

Arterio-venous gradients of free energy change for assessment of systemic and splanchnic perfusion in cardiac surgery patients

OBJECTIVE: Adequacy of organ perfusion depends on sufficient oxygen supply in relation to the metabolic needs. The aim of this study was to evaluate the relationship between gradients of free energy change, and the more commonly used parameter for the evaluation of the adequacy of organ perfusion, such as oxygen-extraction in patients undergoing valve replacement surgery using normothermic cardiopulmonary bypass (CPB). METHODS: In 43 cardiac patients, arterial, mixed venous, and hepato-venous blood samples were taken synchronously after induction of anaesthesia (preCPB), during CPB, and 2 and 7 h after admission to the intensive care unit (ICU+2, ICU+7). Blood gas analysis, cardiac output, and hepato-splanchnic blood flow were measured. Free energy change gradients between mixed venous and arterial (-deltadeltaG(v - a)) and hepato-venous and arterial (-deltadeltaG(hv - a)) compartments were calculated. MEASUREMENTS AND RESULTS: Cardiac index (CI) increased from 1.9 (0.7) to 2.8 (1.3) L/min/m (median, inter-quartile range) (p = 0.001), and hepato-splanchnic blood flow index (HBFI) from 0.6 (0.22) to 0.8 (0.53) L/min/m (p = 0.001). Despite increasing flow, systemic oxygen extraction increased after CPB from 24 (10)% to 35 (10)% at ICU+2 (p = 0.002), and splanchnic oxygen extraction increased during CPB from 37 (19)% to 52 (14)% (p = 0.001), and remained high thereafter. After CPB, high splanchnic and systemic gradients of free energy change gradients were associated with high splanchnic and systemic oxygen extraction, respectively (p = 0.001, 0.033, respectively). CONCLUSION: Gradients of free energy change may be helpful in characterising adequacy of perfusion in cardiac surgery patients independently from measurements or calculations of data from oxygen transport.     

Gadolinium neutron capture brachytherapy (GdNCB), a new treatment method for intravascular brachytherapy

Restenosis is a major problem after balloon angioplasty and stent implantation. The aim of this study is to introduce gadolinium neutron capture brachytherapy (GdNCB) as a suitable modality for treatment of stenosis. The utility of GdNCB in intravascular brachytherapy (IVBT) of stent stenosis is investigated by using the GEANT4 and MCNP4B Monte Carlo radiation transport codes. To study capture rate, Kerma, absorbed dose and absorbed dose rate around a Gd-containing stent activated with neutrons, a 30 mm long, 5 mm diameter gadolinium foil is chosen. The input data is a neutron spectrum used for clinical neutron capture therapy in Studsvik, Sweden. Thermal neutron capture in gadolinium yields a spectrum of high-energy gamma photons, which due to the build-up effect gives an almost flat dose delivery pattern to the first 4 mm around the stent. The absorbed dose rate is 1.33 Gy/min, 0.25 mm from the stent surface while the dose to normal tissue is in order of 0.22 Gy/min, i.e., a factor of 6 lower. To spare normal tissue further fractionation of the dose is also possible. The capture rate is relatively high at both ends of the foil. The dose distribution from gamma and charge particle radiation at the edges and inside the stent contributes to a nonuniform dose distribution. This will lead to higher doses to the surrounding tissue and may prevent stent edge and in-stent restenosis. The position of the stent can be verified and corrected by the treatment plan prior to activation. Activation of the stent by an external neutron field can be performed days after catherization when the target cells start to proliferate and can be expected to be more radiation sensitive. Another advantage of the nonradioactive gadolinium stent is the possibility to avoid radiation hazard to personnel.     

Calbindin D(9k) knockout mice are indistinguishable from wild-type mice in phenotype and serum calcium level

Since the discovery of calbindin D(9k), its role in intestinal calcium absorption has remained unsettled. Further, a wide distribution of calbindin D(9k) among tissues has argued for its biological importance. We discovered a frameshift deletion in the calbindin D(9k) gene in an ES cell line, E14.1, that originated from 129/OlaHsd mice. We produced mice with the mutant calbindin D(9k) gene by injecting the E14.1 ES cell subline into the C57BL/6 host blastocysts and proved that these mice lack calbindin D(9k) protein. Calbindin D(9k) knockout mice were indistinguishable from wild-type mice in phenotype, were able to reproduce, and had normal serum calcium levels. Thus, calbindin D(9k) is not required for viability, reproduction, or calcium homeostasis.     

Aberrant microRNA expression and its implications in the pathogenesis of leukemias

Background

MicroRNAs (miRNAs) are a class of non-coding, endogenous, small RNAs that negatively regulate gene expression by inducing degradation or translational inhibition of target mRNAs. Aberrant expression of miRNAs appears to be a common characteristic of hematological malignancies including leukemias.

Aim

Here we review the available data supporting a role of aberrant expression of miRNAs in the pathogenesis of leukemias including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL).

Conclusions

The expression signatures of miRNAs provide exciting opportunities in the diagnosis, prognosis, and therapy of leukemia. Since miRNAs can function as either oncogenes or tumor suppressor genes in leukemogenesis, the potential of using these small RNAs as therapeutic targets opens up new opportunities for leukemia therapy by either inhibiting or augmenting their activity.     

Comparison of the efficacy of three PubMed search filters in finding randomized controlled trials to answer clinical questions

Objective The aim of this study was to compare the performance of three search methods in the retrieval of relevant clinical trials from PubMed to answer specific clinical questions. Methods Included studies of a sample of 100 Cochrane reviews which recorded in PubMed were considered as the reference standard. The search queries were formulated based on the systematic review titles. Precision, recall and number of retrieved records for limiting the results to clinical trial publication type, and using sensitive and specific clinical queries filters were compared. The number of keywords, presence of specific names of intervention and syndrome in the search keywords were used in a model to predict the recalls and precisions. Results The Clinical queries‐sensitive search strategy retrieved the largest number of records (33) and had the highest recall (41.6%) and lowest precision (4.8%). The presence of specific intervention name was the only significant predictor of all recalls and precisions (P = 0.016). Conclusion The recall and precision of combination of simple clinical search queries and methodological search filters to find clinical trials in various subjects were considerably low. The limit field strategy yielded in higher precision and fewer retrieved records and approximately similar recall, compared with the clinical queries‐sensitive strategy. Presence of specific intervention name in the search keywords increased both recall and precision.     

Role of endothelin-1 in tamoxifen resistance: Mechanism for a new possible treatment strategy in breast cancer

Breast cancer is the prevalent cancer worldwide. Excessive exposure to endogenous estrogen across a woman's lifespan contributes to and may be a causal factor in breast cancer. Tamoxifen is a mixed estrogen agonist and antagonist, which is used in treatment and prevention of breast cancer as an estrogen antagonist. Many patients experience resistance to tamoxifen for which many mechanisms have been suggested. Endothelin-1 acts as a mitogen for human breast fibroblasts and it affects tumor cell proliferation, invasion, angiogenesis, neovascularization, mitogenesis, and apoptosis inhibition. Previous studies have shown that estradiol is effective in inhibiting endothelin synthesis in breast tissue and cardiovascular system. Tamoxifen as an estrogen receptor (ER) agonist in cardiovascular system has a cardioprotective effect and decreases endothelin level as a vasoconstrictor in cardiovascular system. But in breast tissue tamoxifen acts as an ER antagonist. According to the role of endothelin in breast cancer and inhibitory effect of estrogen on endothelin, we hypothesized that tamoxifen causes increasing in endothelin level or endothelin receptors probably by inhibitory effect on ER in breast tissue, leading to tamoxifen resistance. Therefore a combination of tamoxifen with endothelin antagonist seems to be a reasonable therapeutic strategy.