The neuroprotective effect of lactate is not due to improved glutamate uptake after controlled cortical impact in rats

Abstract For many years lactate was considered to be a waste product of glycolysis. Data are accumulating that suggest that lactate is an important energy substrate for neurons during activation. In severe traumatic brain injury (TBI) glutamate release and ischemic cerebral blood flow (CBF) are major factors for a mismatch between energy demand and supply and for neuronal cell death. Although ATP and behavior could be improved by lactate treatment after TBI, no histological correlate nor any linkage to better astrocytic glutamate uptake or CBF as possible mechanisms have been described. We subjected male rats to a controlled cortical impact (CCI; 5?m/sec, 2.5?mm). To study the effects of lactate treatment on lesion volume, glutamate release, and CBF, animals were infused with either NaCl or 100?mM lactate for up to 3?h. The role of endogenous lactate was investigated by inhibiting transport with α-cyano-4-hydroxy-cinnamic acid (4-CIN; 90?mg/kg). Lactate treatment 15?min post-CCI reduced lesion volume from 21.1±2.8?mm(3) to 12.1±1.9?mm(3) at day 2 after CCI. Contusion produced a significant three- to fourfold increase of glutamate in microdialysates, but there was no significant difference between treatments that began 30?min before CCI. In this experiment lesion volume was significantly reduced by lactate at day 7 post-CCI (23.7±4 to 9.3±1-2?mm(3)). CBF increased immediately after CCI and dropped thereafter below baseline in all animals. Lactate infusion 15?min post-CCI elevated CBF for 20?min in 7 of 10 animals, whereas 7 of 8 NaCl-treated animals showed a further CBF decline. Neuroprotection was achieved by lactate treatment following contusion injury, whereas blocking of endogenous lactate transport exerted no adverse effects. Neuroprotection was not achieved by improved glutamate uptake into astrocytes, but was supported by augmented CBF following CCI. Due to its neuroprotective property, lactate might be a beneficial pharmacological treatment for TBI patients.     

Hybrid neurofibroma/schwannoma is overrepresented among schwannomatosis and neurofibromatosis patients

We analyzed the histologic features of peripheral nerve sheath tumors occurring in 14 patients with schwannomatosis. Among a total of 31 tumors, 19 tumors (61%) showed schwannoma-like nodules within a neurofibroma-like tumor, corresponding to hybrid neurofibroma/schwannoma. At least 1 hybrid tumor occurred in 10 of 14 (71%) schwannomatosis patients. We then retrieved cases of hybrid tumors without documented relation to schwannomatosis from our database and identified 41 tumors arising in 23 patients. More than half of these patients (14/23) were reported to suffer from multiple peripheral nerve sheath tumors, favoring a tumor syndrome. Indeed, analysis of clinical records revealed the diagnosis of neurofibromatosis type 2 (NF2) in 26% (6/23), neurofibromatosis type 1 (NF1) in 9% (2/23), definite schwannomatosis in 4% (1/23), and possible schwannomatosis in 13% (3/23) of patients with multiple nerve sheath tumors. Our findings suggest that hybrid neurofibroma/schwannoma represents a common tumor type in schwannomatosis and shows a striking association with neurofibromatoses.     

A novel automated platform for quantifying the extent of skeletal tumour involvement in prostate cancer patients using the Bone Scan Index

Background

Nocturia, a common complaint in aging men and women, is frequently cited as the cause of nocturnal awakenings leading to sleep loss, daytime fatigue, and reduced quality of life (QOL).

Objective

Investigate the association of nocturia with QOL and depressive symptoms among men and women.

Design, setting, and participants

A population-based epidemiologic survey of urologic symptoms among persons aged 30-79 yr. A multistage stratified cluster sample design was used to randomly sample 5503 residents of Boston, MA, USA.

Measurements

Nocturia was defined as a self-report of two or more voiding episodes nightly or having to get up to urinate more than once nightly “fairly often,” “usually,” or “almost always.” QOL was assessed using the physical and mental health component scores of the 12-Item Short-Form Survey (SF-12). Depression was assessed using the Center for Epidemiological Studies Depression Scale. Multiple linear and logistic regression methods were used to model the nocturia and QOL association and to control for confounders.

Results and limitations

Nocturia was associated with decreased SF-12 scores for both the physical and mental health components after multivariate adjustment. Nocturia was also associated with increased odds of depressive symptoms (men: adjusted odds ratio [OR]: 2.79; 95% confidence interval [CI], 1.81-4.31; women: adjusted OR: 1.80; 95% CI, 1.29-2.51). Among women who reported sleep interference due to urologic symptoms, nocturia was associated with a threefold increase in odds of depression. In this cross-sectional analysis, the temporal sequence of causality of the nocturia and depression association could not be assessed.

Conclusions

Nocturia is associated with decreased QOL and with an increased prevalence of depressive symptoms in both men and women.     

Effects of a mandatory basic life support training programme on the no-flow fraction during in-hospital cardiac resuscitation: An observational study

Aim of the study

Many hospitals have basic life support (BLS) training programmes, but the effects on the quality of chest compressions are unclear. This study aimed to evaluate the no-flow fraction (NFF) during BLS provided by standard care nursing teams over a five-year observation period during which annual participation in the BLS training was mandatory.

Methods

All healthcare professionals working at Dresden University Hospital were instructed in BLS and automated external defibrillator (AED) use according to the current European Resuscitation Council guidelines on an annual basis. After each cardiac arrest occurring on a standard care ward, AED data were analyzed. The time without chest compressions during the period without spontaneous circulation (i.e., the no-flow fraction) was calculated using thoracic impedance data.

Results

For each year of the study period (2008–2012), a total of 1454, 1466, 1487, 1432, and 1388 health care professionals, respectively, participated in the training. The median no-flow fraction decreased significantly from 0.55 [0.42; 0.57] (median [25‰; 75‰]) in 2008 to 0.3 [0.28; 0.35] in 2012. Following revision of the BLS curriculum after publication of the 2010 guidelines, cardiac arrest was associated with a higher proportion of patients achieving ROSC (72% vs. 48%, P = 0.025) but not a higher survival rate to hospital discharge (35% vs. 19%, P = 0.073).

Conclusion

The NFF during in-hospital cardiac resuscitation decreased after establishment of a mandatory annual BLS training for healthcare professionals. Following publication of the 2010 guidelines, more patients achieved ROSC after in-hospital cardiac arrest.