What is still missing in acute-phase treatment of stroke: a prospective observational study

Early recognition of stroke symptoms and activation of emergency medical service (EMS) positively affects prognosis after a stroke. To assess stroke awareness among stroke patients and medical personnel in the catchment area of Verona Hospital and how it affects stroke care, we prospectively studied timing of acute stroke care in relation to patients’ characteristics. Patients admitted to Medical Departments of Verona University Hospital between January 1st and December 31st 2009 with a diagnosis of TIA or stroke were enrolled. Outcome measures were: time between (i) symptoms onset and hospital arrival, (ii) hospital arrival and brain CT scan, blood examination, ECG and neurological evaluation. The following patient/event characteristics were also collected: means of hospital arrival, sex, age, degree of disability, type of event (first or recurrent) and acute-phase treatment. Of 578 patients providing complete information, 60 % arrived to the emergency department with the EMS (EMS+ group), while 40 % arrived on their own (EMS?). EMS+ group was older than EMS? (mean age 76.2, SD 13.2, vs. 72.3, SD 13, respectively), displayed more severe symptoms (mRS 4 vs. 2) and shorter time interval between symptoms onset and hospital arrival, hospital arrival and CT scan, ECG, laboratory tests and neurological evaluation (p < 0.0001); 22 % of the EMS+ patients were stroke recurrences versus 29 % of the EMS? (p = 0.058); 85 % of thrombolised patients were EMS+. We conclude that there is a lack of awareness of stroke symptoms and risks of recurrence even among patients who already had a stroke and among medical personnel.     

What is the best treatment of drug-resistant trigeminal neuralgia in patients affected by multiple sclerosis? A literature analysis of surgical procedures

Objective

Drug-resistant trigeminal neuralgia (TN) can complicate the clinical course of patients affected by multiple sclerosis (MS). Various surgical procedures have been reported for the treatment of this condition, but there is no agreement on the best management of these patients. To our knowledge, there is no critical literature analysis focusing on this particular topic. The aim of this study was to evaluate the clinical outcome of different surgical procedures utilized for drug-resistant TN in MS patients.

Methods

We reviewed the literature about the studies reporting on surgical treatment of drug-resistant TN in MS patients. Case reports and case series less than 4 patients were excluded from the analysis. Nineteen studies were selected for the statistical analysis. To reduce the variability of the data, the selected studies were evaluated for the following outcome parameters: acute pain relief rate (APR), rate of recurrence (RR), pain free at follow-up rate (PF at FU) and complication rate (CR). For the statistical analysis, chi-square statistic, using the Fisher's exact test was utilized.

Results

There was no procedure statistically superior in terms of APR rate in MS patients following the surgical treatment of TN. The highest RR was observed for percutaneous balloon compression (PBC) (60.2 ± 14.4%). This result was statistically significant when compared to gamma knife surgery (GKS) (p = 0.0129) and microvascular decompression (MVD) (p = 0.0281). MVD together with percutaneous radiofrequency rhizothomy (PRR) was associated with a statistically better PF at FU rate (56.5 ± 16.8% and 73.5 ± 14.2%, respectively). However PBC and MVD showed statistical significant minor CR compared to other techniques (no complications and 18.7 ± 17.4%, respectively).

Conclusion

Our study shows no differences in the short term results among different procedures for TN in MS patients. Each technique demonstrate advantages and limits in terms of long term pain, recurrence rate and complication rate. Each patient should be accurately informed on pros and cons of each procedure in order to be involved in the most appropriate choice.     

Primary multicentric anaplastic pleomorphic xanthoastrocytoma with atypical features

Pleomorphic xanthoastrocytoma (PXA) is a rare tumor with good prognosis after surgery. Few cases of anaplastic PXA (either de novo or secondary to transformation of a recurrent low grade PXA) have been reported. Moreover, primary anaplastic PXA with dissemination at diagnosis has been described only in two patients, to our knowledge. We report the first case of primary multicentric anaplastic PXA and discuss its atypical features and the pertinent literature.     

Efficacy of tolvaptan on advanced chronic kidney disease with heart failure: a randomized controlled trial

Clinical and Experimental Nephrology - Tolvaptan (TLV) is reported to improve diuretic effects in patients with chronic kidney disease (CKD) when furosemide (FUR) is not sufficiently effective....     

Contribution of equilibrative nucleoside transporters 1 and 2 to gemcitabine uptake in pancreatic cancer cells

Hepatic arterial infusion (HAI) chemotherapy is expected to be a more effective and safer method to treat the hepatic metastasis of pancreatic cancer than intravenous (iv) administration because of higher tumor exposure and lower systemic exposure. To clarify the uptake mechanism of nucleoside anticancer drugs, including gemcitabine (GEM), in pancreatic cancer, we investigated the uptakes of radiolabeled uridine (a general substrate of nucleoside transporters) and GEM in pancreatic cancer cell lines MIA‐PaCa2 and As‐PC1. Uridine uptake was inhibited by non‐labeled GEM and also by S‐(4‐nitrobenzyl)‐6‐thioinosine (NBMPR; an inhibitor of equilibrative nucleoside transporters, ENTs) in a concentration‐dependent manner, suggesting that ENTs contribute to uridine uptake in pancreatic cancer cells. As for GEM, saturable uptake was mediated by high‐ and low‐affinity components with K_m values of micromolar and millimolar orders, respectively. Uptake was inhibited in a concentration‐dependent manner by NBMPR and was sodium ion‐independent. Moreover, the concentration dependence of uptake in the presence of 0.1 μM NBMPR showed a single low‐affinity site. These results indicated that the high‐ and low‐affinity sites correspond to hENT1 and hENT2, respectively. The results indicated that at clinically relevant hepatic concentrations of GEM in GEM‐HAI therapy, the metastatic tumor exposure of GEM is predominantly determined by hENT2 under unsaturated conditions, suggesting that hENT2 expression in metastatic tumor would be a candidate biomarker for indicating anticancer therapy with GEM‐HAI.     

The impact of surgical extent and sex on the hepatic metastasis of colon cancer

Purpose

Extensive oncological surgeries were previously suggested to increase cancer recurrence rates. We herein studied the impact of different surgical procedures and sex on colorectal cancer liver metastasis, employing several tumor inoculation approaches in BALB/c mice.

Methods

Experimental hepatic metastases of the syngeneic CT26 colorectal cancer line were induced either by intra-portal inoculation or intra-splenic inoculation, employing different tumor loads. Following intra-splenic inoculation, the entire spleen or an injected hemi-spleen was removed. Additionally, the magnitude of the surgical trauma accompanying the injection procedure was manipulated.

Results

Increasing the surgical trauma by adding laparotomy or extending the length of the surgery and hypothermia did not significantly affect the number of liver metastases or liver weight for any of the injection methods and tumor loads. The development of metastasis was significantly greater in males than in females under all conditions studied—a difference not explained by the direct effects of sex hormones on in vitro CT26 proliferation or vitality.

Conclusion

Concurring with less controlled clinical observations, the surgical extensiveness did not significantly affect CT26 hepatic metastasis, potentially due to a ceiling effect of the surgical trauma on the metastatic process. The sexual dimorphism observed for the CT26 metastasis should be investigated in the context of surgical stress and considering anti-CT26 immunoreactivity.     

Concentration Dependency in Nicotine Skin Penetration Flux from Aqueous Solutions Reflects Vehicle Induced Changes in Nicotine Stratum Corneum Retention

Purpose

This study sought to understand the mechanism by which the steady state flux of nicotine across the human skin from aqueous solutions is markedly decreased at higher nicotine concentrations.

Methods

Nicotine’s steady state flux through human epidermis and its amount in the stratum corneum for a range of aqueous nicotine solutions was determined using Franz diffusion cells, with the nicotine analysed by high performance liquid chromatography (HPLC). Nicotine’s thermodynamic activity in the various solutions was estimated from its partial vapour pressure and stratum corneum hydration was determined using a corneometer. The amount of nicotine retained in the stratum corneum was estimated from the nicotine amount found in individual stratum corneum tape strips and a D-Squame determined weight for each strip.

Results

The observed steady state flux of nicotine across human epidermis was found to show a parabolic dependence on nicotine concentration, with the flux proportional to its thermodynamic activity up to a concentration of 48% w/w. The nicotine retention in the stratum corneum showed a similar dependency on concentration whereas the diffusivity of nicotine in the stratum corneum appeared to be concentration independent. This retention, in turn, could be estimated from the extent of stratum corneum hydration and the nicotine concentration in the applied solution and volume of water in the skin.

Conclusions

Nonlinear dependency of nicotine skin flux on its concentration results from a dehydration induced decrease in its stratum corneum retention at higher concentration and not dehydration induced changes nicotine diffusivity in the stratum corneum.