Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-11C-verapamil and PET.

The multidrug efflux transporter P-glycoprotein (P-gp) is expressed in high concentrations at the blood-brain barrier (BBB) and is believed to be implicated in resistance to central nervous system drugs. We used small-animal PET and (R)-11C-verapamil together with tariquidar, a new-generation P-gp modulator, to study the functional activity of P-gp at the BBB of rats. To enable a comparison with human PET data, we performed kinetic modeling to estimate the rate constants of radiotracer transport across the rat BBB. METHODS: A group of 7 Wistar Unilever rats underwent paired (R)-11C-verapamil PET scans at an interval of 3 h: 1 baseline scan and 1 scan after intravenous injection of tariquidar (15 mg/kg, n = 5) or vehicle (n = 2). RESULTS: After tariquidar administration, the distribution volume (DV) of (R)-11C-verapamil was 12-fold higher than baseline (3.68 +/- 0.81 vs. 0.30 +/- 0.08; P = 0.0007, paired t test), whereas the DVs were essentially the same when only vehicle was administered. The increase in DV could be attributed mainly to an increased influx rate constant (K1) of (R)-11C-verapamil into the brain, which was about 8-fold higher after tariquidar. A dose-response assessment with tariquidar provided an estimated half-maximum effect dose of 8.4 +/- 9.5 mg/kg. CONCLUSION: Our data demonstrate that (R)-11C-verapamil PET combined with tariquidar administration is a promising approach to measure P-gp function at the BBB.     

Histopathologic changes in oral mucosa of Yemenis addicted to water-pipe and cigarette smoking in addition to takhzeen al-qat.

BACKGROUND: Because the clinicopathologic effects of takhzeen al-qat are similar to those induced by smoking, the aim of this paper was to study the oral effect of 3 bad oral habits: takhzeen al-qat and cigarette and water-pipe smoking. STUDY DESIGN: This study was done on 33 Yemeni chronic qat users grouped as heavy cigarette smokers (GI), nonsmokers (GII) and water-pipe smokers (GIII). In all cases (n = 33) 2 biopsies were taken (n = 66), one from the buccal mucosa at the chewing side and the other from a similar mucosa at the contralateral (nonexposed) side. Biopsies were prepared for routine H&E staining. RESULTS: Acanthosis appeared in 88% and 0%, abnormal rete ridges in 70% and 3%, hyperparakeratosis in 67% and 0%, and epithelial dysplasia in 30% and 0% of the chewing and nonchewing sides, respectively, in the 3 groups. Epithelial dysplasia appeared in 41% of GI and GIII (smokers) but in only 9% of GII (nonsmokers). CONCLUSIONS: Takhzeen al-qat causes distinct histopathologic changes in the oral mucosa at the side of chewing, such as acanthosis, abnormal rete ridges, and hyperparakeratosis. The association between takhzeen al-qat and cigarette or water-pipe smoking may increase the risk of epithelial dysplasia.     

The yield of stool testing in hospital-onset diarrhea: Has evidence changed practice?

Introduction: Aside from examination for Clostridium difficile, the yield of stool testing in hospital-onset diarrhea is poor. Clinical practice guidelines discourage overzealous stool testing in patients with diarrhea that develops after the third hospital day. However, the adoption of this recommendation into clinical practice is limited. Furthermore, the effect of microbiology laboratory improvements on hospital-onset diarrhea testing is largely unknown. Methods: A retrospective cohort study was conducted in a university-affiliated community-hospital and included all adult inpatients who developed diarrhea after hospitalization. Results: 132 adult patients (53% female) developed diarrhea after hospitalization in 2013. The cohort’s mean age was 55.6 years. 46.2% of patients developed diarrhea in the first 3 days of hospitalization. Testing for parasites was negative in all examined 67 samples. Testing for C. difficile was positive in 13 cases (10.8%) out of 120 tested samples. Testing for other pathogens was positive in 1 sample (Campylobacter) out of 129 samples. Stool samples tested in the first 3 days of hospitalization were more likely to be positive (64.3 vs 35.7%, p = 0.1). Change in management was reported in 9 out of 14 patients (64.3%) with positive stool testing compared with 31 out of 118 patients (26.3%) with negative stool testing, p = 0.01. Conclusion: Despite improvements in stool samples’ testing, the yield continues to be low, especially in hospital-onset diarrhea past the third hospital day. Physicians’ embracement of the ‘3-day rule’ continues to be poor.     

Selenium Deficiency After Bariatric Surgery,Incidence and Symptoms: a Systematic Review and Meta-Analysis

Obesity Surgery - This study review the prevalence of selenium deficiency after bariatric surgery, incidence, and symptoms. A systematic literature search and meta-analysis was performed...     

Gastric volvulus caused by paraesophageal hernia complicating mid-trimester pregnancy

A 36-year-old woman, who was 19 weeks pregnant presented with epigastric pain and a one-week history of repeated vomiting. Endoscopy revealed twisted stomach. CT scan of the chest showed figure of eight stomach consistent with gastric volvulus. Confirmation of diagnosis was made by laparatomy in which reduction of the oedematous stomach and excision of ischemic omental patch and repair of a huge paraesophageal hernia were performed. Two days after operation, abortion took place. Few days later, rapid deterioration in renal and hepatic function occurred followed by maternal death.     

Prostate cancer measurements on serial MRI during active surveillance: it’s time to be PRECISE

Objective:The PRECISE criteria for reporting multiparametric MRI in patients on active surveillance (AS) for prostate cancer (PCa) score the likelihood of clinically significant change over time using a 1–5 scale, where 4 or 5 indicates radiological progression. According to the PRECISE recommendations, the index lesion size can be reported using different definitions of volume (planimetry or ellipsoid formula) or by measuring one or two diameters. We compared different measurements using planimetry as the reference standard and stratified changes according to the PRECISE scores.Methods:We retrospectively analysed 196 patients on AS with PCa confirmed by targeted biopsy who had two MR scans (baseline and follow-up). Lesions were measured on T₂ weighted imaging (T₂WI) according to all definitions. A PRECISE score was assessed for each patient.Results:The ellipsoid formula exhibited the highest correlation with planimetry at baseline (ρ = 0.97) and follow-up (ρ = 0.98) imaging, compared to the biaxial measurement and single maximum diameter. There was a significant difference (p < 0.001) in the yearly percentage volume change between radiological regression/stability (PRECISE 2–3) and progression (PRECISE 4–5) for planimetry (39.64%) and for the ellipsoid formula (46.78%).Conclusion:The ellipsoid formula could be used to monitor tumour growth during AS. Evidence of a significant yearly percentage volume change between radiological regression/stability (PRECISE 2-3) and progression (PRECISE 4-5) has been also observed.Advances in knowledge:The ellipsoid formula is a reasonable surrogate for planimetry in capturing tumour volume changes on T₂WI in patients on imaging-led AS. This is also associated with radiological changes using the PRECISE recommendations.     

Sustained release and enhanced oral bioavailability of rivaroxaban by PLGA nanoparticles with no food effect

Journal of Thrombosis and Thrombolysis - The purpose of the currents study was to enhance bioavailability of rivaroxaban (RXB) and reduce the food effect. RXB loaded PLGA nanoparticles...     

Ptosis postcardiac surgery: a case of pituitary apoplexy

We present a patient in whom ptosis and third cranial nerve palsy developed postcoronary artery bypass grafting, and discuss the management of pituitary apoplexy postcardiac surgery.