Human ClCa1 modulates anionic conduction of calcium-dependent chloride currents

Proteins of the CLCA gene family including the human ClCa1 (hClCa1) have been suggested to constitute a new family of chloride channels mediating Ca²⁺-dependent Cl⁻ currents. The present study examines the relationship between the hClCa1 protein and Ca²⁺-dependent Cl⁻ currents using heterologous expression of hClCa1 in HEK293 and NCIH522 cell lines and whole cell recordings. By contrast to previous reports claiming the absence of Cl⁻ currents in HEK293 cells, we find that HEK293 and NCIH522 cell lines express constitutive Ca²⁺-dependent Cl⁻ currents and show that hClCa1 increases the amplitude of Ca²⁺-dependent Cl⁻ currents in those cells. We further show that hClCa1 does not modify the permeability sequence but increases the Cl⁻ conductance while decreasing the G _SCN−/ G _Cl− conductance ratio from ∼2–3 to ∼1. We use an Eyring rate theory (two barriers, one site channel) model and show that the effect of hClCa1 on the anionic channel can be simulated by its action on lowering the first and the second energy barriers. We conclude that hClCa1 does not form Ca²⁺-dependent Cl⁻ channels per se or enhance the trafficking/insertion of constitutive channels in the HEK293 and NCIH522 expression systems. Rather, hClCa1 elevates the single channel conductance of endogenous Ca²⁺-dependent Cl⁻ channels by lowering the energy barriers for ion translocation through the pore.     

Intra-arrest cooling with delayed reperfusion yields higher survival than earlier normothermic resuscitation in a mouse model of cardiac arrest

BACKGROUND: Therapeutic hypothermia (TH) represents an important method to attenuate post-resuscitation injury after cardiac arrest. Laboratory investigations have suggested that induction of hypothermia before return of spontaneous circulation (ROSC) may confer the greatest benefit. We hypothesized that a short delay in resuscitation to induce hypothermia before ROSC, even at the expense of more prolonged ischemia, may yield both physiological and survival advantages. METHODS: Cardiac arrest was induced in C57BL/6 mice using intravenous potassium chloride; resuscitation was attempted with CPR and fluid administration. Animals were randomized into three groups (n=15 each): a normothermic control group, in which 8 min of arrest at 37 degrees C was followed by resuscitation; an early intra-arrest hypothermia group, in which 6.5 min of 37 degrees C arrest were followed by 90s of cooling, with resuscitation attempted at 30 degrees C (8 min total ischemia); and a delayed intra-arrest hypothermia group, with 90s cooling begun after 8 min of 37 degrees C ischemia, so that animals underwent resuscitation at 9.5 min. RESULTS: Animals treated with TH demonstrated improved hemodynamic variables and survival compared to normothermic controls. This was the case even when comparing the delayed intra-arrest hypothermia group with prolonged ischemia time against normothermic controls with shorter ischemia time (7-day survival, 4/15 vs. 0/15, p<0.001). CONCLUSIONS: Short resuscitation delays to allow establishment of hypothermia before ROSC appear beneficial to both cardiac function and survival. This finding supports the concept that post-resuscitation injury processes begin immediately after ROSC, and that intra-arrest cooling may serve as a useful therapeutic approach to improve survival.     

Pre-hospital treatment of acute poisonings in Oslo

Background

Cardiac arrest is the leading cause of mortality in Canada, and the overall survival rate for out-of-hospital cardiac arrest rarely exceeds 5%. Bystander cardiopulmonary resuscitation (CPR) has been shown to increase survival for cardiac arrest victims. However, bystander CPR rates remain low in Canada, rarely exceeding 15%, despite various attempts to improve them. Dispatch-assisted CPR instructions have the potential to improve rates of bystander CPR and many Canadian urban communities now offer instructions to callers reporting a victim in cardiac arrest. Dispatch-assisted CPR instructions are recommended by the International Guidelines on Emergency Cardiovascular Care, but their ability to improve cardiac arrest survival remains unclear.

Methods/Design

The overall goal of this study is to better understand the factors leading to successful dispatch-assisted CPR instructions and to ultimately save the lives of more cardiac arrest patients. The study will utilize a before-after, prospective cohort design to specifically: 1) Determine the ability of 9-1-1 dispatchers to correctly diagnose cardiac arrest; 2) Quantify the frequency and impact of perceived agonal breathing on cardiac arrest diagnosis; 3) Measure the frequency with which dispatch-assisted CPR instructions can be successfully completed; and 4) Measure the impact of dispatch-assisted CPR instructions on bystander CPR and survival rates. The study will be conducted in 19 urban communities in Ontario, Canada. All 9-1-1 calls occurring in the study communities reporting out-of-hospital cardiac arrest in victims 16 years of age or older for which resuscitation was attempted will be eligible. Information will be obtained from 9-1-1 call recordings, paramedic patient care reports, base hospital records, fire medical records and hospital medical records. Victim, caller and system characteristics will be measured in the study communities before the introduction of dispatch-assisted CPR instructions (before group), during the introduction (run-in phase), and following the introduction (after group).

Discussion

The study will obtain information essential to the development of clinical trials that will test a variety of educational approaches and delivery methods for telephone cardiopulmonary resuscitation instructions. This will be the first study in the world to clearly quantify the impact of dispatch-assisted CPR instructions on survival to hospital discharge for out-of-hospital cardiac arrest victims.

Trial Registration

ClinicalTrials.gov NCT00664443     

Funktionelle Ergebnisse nach temporärer Dauerableitung der hypokontraktilen Blase

BACKGROUND: Impaired bladder emptying is a common problem in older people and a challenging task in treatment. Conservative and medical treatment options have shown beneficial effects on micturition; however, in a substantial number of patients the effectiveness of these therapies is disappointing. In the end the decompensated bladder needs indwelling catheterisation. To study the effects on the detrusor function, we analysed the urodynamic data of 31 patients during long-term bladder drainage retrospectively. PATIENTS AND METHODS: All 17 female and 14 male patients showed impaired detrusor contractility, enlarged bladder capacity, decreased sensitivity and a high post-void residual urine volume (PVR). After exclusion of an acute pathology, the patients were treated continously with a suprapubic catheter for an average of 13.1 weeks. By urodynamic measurements before and after the drainage period, we analysed the filling parameters, pressure-flow patterns, PVR and detrusor contractility. RESULTS: At the end of the drainage period, significant changes in the detrusor function were obvious. Compared with the pre-treatment situation, the bladder volume at first desire to void decreased from 306.92 ml to 281.7 ml and the maximum bladder capacity from 691.8 ml to 496.8 ml, respectively. The compliance of the detrusor muscle diminished in the same period of time from 65.6 ml/cmH2O to 51.8 ml/cmH(2)O. The PVR dropped by 227.2 ml in average. The maximum flow rate was 9.4 ml/s, and the maximum detrusor pressure increased slightly up to 23.6 cmH(2)O. CONCLUSION: The continuous drainage of the bladder results in significant changes in the motoric as well as sensoric detrusor function. The reduced bladder capacity and the decreased PVR might be indications of a regenerating process of the detrusor. The long-term drainage of the bladder shows beneficial and therefore therapeutic effects. It still remains to be investigated on a functional as well as structural basis to what extent age, gender and pathogenesis influences the rehabilitation of the detrusor.     

Patients' acceptance of the deltoid application of risperidone long-acting injection

Objective: Recently risperidone long-acting injection (RLAI) was approved for alternative injection into the deltoid muscle in addition to the already established injection into the gluteal muscle. For the first time two different injection locations of a long-acting antipsychotic injection can be offered to patients. Their actual acceptance is of key interest. Experimental procedures: We surveyed 60 patients stabilized on gluteal RLAI therapy in our depot outpatient clinic. Participants were offered the possibility of switching to the alternative deltoid injection in a standardized manner. Prior to switching patients scored the extent of perceived pain and experienced level of shame through the present gluteal injection therapy on a 7-point-scale. Patients choosing to switch were followed up after three months and asked to report on their individual experience. Results: Switching to the deltoid application was chosen by 34 out of 60 patients. Three months later 15 patients were still receiving deltoid injections. The main reason for their staying with the deltoid injection was improved practicability as reported by these patients and 13 out of 15 patients clearly preferred the new location over the gluteal application. The main reason for returning to the gluteal injection was the pain experienced through the injection in the deltoid. Patients' initial decision whether to switch was not correlated with either perceived pain or the experienced level of shame through the preceding gluteal injections. Conclusions: The application of RLAI in the deltoid muscle is viewed as an alternative to the injection in the gluteal muscle by a considerable number of patients. Nevertheless, some patients experience increased injection pain through this application location while others perceive the switch as beneficial in terms of practicability. Therefore offering both injection locations with their respective pros and cons should become standard in the RLAI treatment offered.