Phenothiazines and haloperidol block Ca-activated K channels in rat forebrain synaptosomes

Ca-dependent, K-stimulated 86Rb efflux, a measure of Ca-activated K conductance in rat brain synaptosomes, was blocked by phenothiazines and haloperidol. Micromolar concentrations of the phenothiazines, fluphenazine and trifluoperazine, and haloperidol, a non-phenothiazine antipsychotic and calmodulin antagonist, selectively inhibited the Ca-activated K channels. The IC50 values of all three agents for inhibition of the Ca-activated K channels was on the order of 0.5-1 microM. Measurements of K-stimulated 45Ca uptake indicated that the effects of these agents on Ca-activated K channels was not due to inhibition of Ca influx through voltage-gated Ca channels. Sulpiride, a potent antipsychotic with weak anti-calmodulin activity, was a relatively weak inhibitor of Ca-activated K channels. Calmidazolium (compound R-24571) and W7, two non-phenothiazine calmodulin antagonists, did not selectively inhibit Ca-activated K channels. Biphasic dose response curves for inhibition of the Ca-dependent, K-stimulated 86Rb efflux by the phenothiazines raise the possibility that there may be two kinds of Ca-activated K channels in rat brain presynaptic terminals, with different sensitivities to the phenothiazines. These results demonstrate that two phenothiazines and haloperidol are potent and relatively selective inhibitors of Ca-activated K channels in nerve endings. This inhibition does not appear to be mediated by calmodulin or by dopamine receptors.     

Anti-Xa activity after subcutaneous administration of dalteparin in ICU patients with and without subcutaneous oedema: a pilot study

Introduction  

Intensive care unit (ICU) patients often suffer from subcutaneous oedema, due to administration of large fluid volumes and the underlying pathophysiological condition. It is unknown whether the presence of subcutaneous oedema impairs the absorption of dalteparin, a low molecular weight heparin, when it is given by subcutaneous administration for venous thromboembolism prophylaxis. The objective of this study is to compare the anti-Xa activity of dalteparin after subcutaneous administration in ICU patients with and without subcutaneous oedema.     

Enteroatmospheric fistula management by endoscopic gastrostomy PEG tube

Management of small‐bowel fistulas which are in an open abdomen and have no soft tissue overlay or a fistula tract involves many complications and challenges. Controlling the local leakage of enteric contents has a central role in the success of medical treatment. There are several methods to deal with fistula discharge but unfortunately, the technical solutions only partially address such problems and a definitive management of fistula discharge still remains an insoluble challenge. We describe a simple and cheap method to control fistula leakage by using a percutaneous endoscopic gastrostomy tube.     

Trends in treatment and overall survival among patients with proximal esophageal cancer

BACKGROUND The management of proximal esophageal cancer differs from that of tumors located in the mid and lower part of the esophagus due to the close vicinity of vital structures. Non-surgical treatment options like radiotherapy and definitive chemoradiation(CRT) have been implemented. The trends in(non-)surgical treatment and its impact on overall survival(OS) in patients with proximal esophageal cancer are unclear, related to its rare disease status. To optimize treatment strategies and counseling of patients with proximal esophageal cancer,it is therefore essential to gain more insight through real-life studies.AIM To establish trends in treatment and OS in patients with proximal esophageal cancer.METHODS In this population-based study, patients with proximal esophageal cancer diagnosed between 1989 and 2014 were identified in the Netherlands Cancer Registry. The proximal esophagus consists of the cervical esophagus and the upper thoracic section, extending to 24 cm from the incisors. Trends in radiotherapy, chemotherapy, and surgery, and OS were assessed. Analyses were stratified by presence of distant metastasis. Multivariable Cox proportional hazards regression analyses was performed to assess the effect of period of diagnosis on OS, adjusted for patient, tumor, and treatment characteristics.RESULTS In total, 2783 patients were included. Over the study period, the use of radiotherapy, resection, and CRT in non-metastatic disease changed from 53%,23%, and 1% in 1989-1994 to 21%, 9%, and 49% in 2010-2014, respectively. In metastatic disease, the use of chemotherapy and radiotherapy increased over time. Median OS of the total population increased from 7.3 mo [95% confidence interval(CI): 6.4-8.1] in 1989-1994 to 9.5 mo(95%CI: 8.1-10.8) in 2010-2014(logrank P 0.001). In non-metastatic disease, 5-year OS rates improved from 5%(95%CI: 3%-7%) in 1989-1994 to 13%(95%CI: 9%-17%) in 2010-2014(logrank P 0.001). Multivariable regression analysis demonstrated a significant treatment effect over time on survival. In metastatic disease, median OS was 3.8 mo(95%CI:2.5-5.1) in 1989-1994, and 5.1 mo(95%CI: 4.3-5.9) in 2010-2014(logrank P = 0.26).CONCLUSION OS significantly improved in non-metastatic proximal esophageal cancer, likely to be associated with an increased use of CRT. Patterns in metastatic disease did not change significantly over time.     

Iron:An emerging factor in colorectal carcinogenesis

The carcinogenic potential of iron in colorectal cancer(CRC) is not fully understood.Iron is able to undergo reduction and oxidation,making it important in many physiological processes.This inherent redox property of iron,however,also renders it toxic when it is present in excess.Iron-mediated generation of reactive oxygen species via the Fenton reaction,if uncontrolled,may lead to cell damage as a result of lipid peroxidation and oxidative DNA and protein damage.This may promote carcinogenesis through incr...