Accumulation of Vitamin A in the Hepatic Stellate Cell of Arctic Top Predators

We performed a systematic characterization of the hepatic vitamin A storage in mammals and birds of the Svalbard archipelago and Greenland. The liver of top predators, including polar bear, arctic fox, bearded seal, and glaucous gull, contained about 10–20 times more vitamin A than the liver of all other arctic animals studied, as well as their genetically related continental top predators. The values are also high compared to normal human and experimental animals like mouse and rat. This massive amount of hepatic vitamin A was located in large autofluorescent lipid droplets in hepatic stellate cells (HSCs; also called vitamin A‐storing cells, lipocytes, interstitial cells, fat‐storing cells, or Ito cells). The droplets made up most of the cells' cytoplasm. The development of such an efficient vitamin A‐storing mechanism in HSCs may have contributed to the survival of top predators in the extreme environment of the arctic. These animals demonstrated no signs of hypervitaminosis A. We suggest that HSCs have capacity to take‐up and store large amounts of vitamin A, which may play a pivotal role in maintenance of the food web, food chain, biodiversity, and eventually ecology of the arctic. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.     

Do expert patients get better treatment than others? Agency discrimination and statistical discrimination in obstetrics

We address models that can explain why expert patients (obstetricians, midwives and doctors) are treated better than non-experts (mainly non-medical training). Models of statistical discrimination show that benevolent doctors treat expert patients better, since experts are better at communicating with the doctor. Agency theory suggests that doctors have an incentive to limit hospital costs by distorting information to non-expert patients, but not to expert patients.The hypotheses were tested on a large set of data, which contained information about the highest education of the parents, and detailed medical information about all births in Norway during the period 1967-2005 (Medical Birth Registry). The empirical analyses show that expert parents have a higher rate of Caesarean section than non-expert parents. The educational disparities were considerable 40 years ago, but have become markedly less over time. The analyses provide support for statistical discrimination theory, though agency theory cannot be totally excluded.     

Routine pelvic MRI using phased-array coil for detection of extraprostatic tumour extension: accuracy and clinical significance

Objectives

To determine the accuracy and assess the clinical significance of surface-coil 1.5-T magnetic resonance imaging (MRI) for the detection of locally advanced prostate cancer (PCa).

Methods

Between December 2007 and January 2010, we examined 209 PCa patients (mean age?=?62.5 years) who were consecutively treated with robot-assisted laparoscopic prostatectomy and prospectively staged by MRI. One hundred and thirty-five patients (64.6 %) had locally advanced disease. Conventional clinical tumour stage and MRI-assessed tumour stage were compared with histopathological tumour stage (pT). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy (OA) were calculated using pT as the “gold standard”. Overstaged and understaged cases at MRI were reviewed.

Results

Sensitivity, specificity, PPV, NPV and OA for the detection of locally advanced disease were 25.9, 95.9, 92.1, 41.2 and 50.5 % and 56.3, 82.2, 85.4, 50.4 and 65.4 % for clinical staging and MRI, respectively. Among patients understaged at MRI, the resection margins were free in 64.4 % of the cases (38/59).

Conclusions

Although the accuracy was limited, the detection of locally advanced disease improved substantially when MRI was added to routine clinical staging. The majority of the understaged patients nevertheless achieved free margins. When assessing the clinical significance of MRI staging the extent of extraprostatic extension has to be considered.

Key Points

? MRI substantially improves detection of locally advanced prostate cancer ? MRI has limited overall staging accuracy ? Most T3 cancers unrecognised at MRI still achieved free resection margins ? Assessing the true clinical contribution of MRI remains challenging     

Radiolabelling and PET brain imaging of the α1-adrenoceptor antagonist Lu AE43936

Cerebral α₁-adrenoceptors are a common target for many antipsychotic drugs. Thus, access to positron emission tomography (PET) brain imaging of α₁-adrenoceptors could make important contributions to the understanding of psychotic disorders as well as to the pharmacokinetics and occupancy of drugs targeting the α₁-adrenoceptors. However, so far no suitable PET radioligand has been developed for brain imaging of α₁-adrenoceptors. Here, we report the synthesis of both enantiomers of the desmethyl precursors of the high affinity α₁-adrenoceptor ligand Lu AE43936 (1). The two enantiomers of 1 were subsequently [¹¹C] radiolabelled and evaluated for brain uptake and binding by PET imaging in Danish Landrace pigs. (S)-[¹¹C]-1 and (R)-[¹¹C]-1 showed very limited brain uptake. Pre-treatment with cyclosporine A (CsA) resulted in a large increase in brain uptake, indicating that (R)-[¹¹C]-1 is a substrate for active efflux-transporters. This was confirmed in Madin Darby canine kidney (MDCK) cells overexpressing permeability glycoprotein (Pgp). In conclusion, the limited brain uptake of both (S)-[¹¹C]-1 and (R)-[¹¹C]-1 in the pig brain necessitates the search for alternative radioligands for in vivo PET brain imaging of α₁-adrenoceptors.     

Autotransplantation of Teeth in 215 Patients: A Follow-up Study

Objective:To evaluate the success rate of autotransplantation of teeth in consecutive patients and to analyze factors affecting the outcome.Materials and Methods:The subjects consisted of 215 consecutive patients (101 women and 114 men; aged 9.1–56.4 years, median age 15.2 years [P₁₀  =  11.4, P₉₀  =  19.7]) who had undergone transplantation of a total of 269 teeth, all by the same surgeon. In patients with multiple transplants, only the first transplant was included, to ensure that all transplanted teeth were independent units. The transplants were recorded as unsuccessful if the tooth had been extracted or was surviving but with root resorption or ankylosis. The interval between transplantation and final follow-up was a median 4.8 years (P₁₀  =  2.0, P₉₀  =  5.5) for successful transplants and a median of 2.4 years (P₁₀  =  0.4, P₉₀  =  7.7) for unsuccessful transplants.Results:One-hundred seventy-five (81%) of the transplantations were recorded as successful and 40 (19%) as unsuccessful. Twenty-five teeth had been extracted and 15 had survived but did not fulfill the criteria for success.Conclusions:The success rate of 215 consecutively transplanted teeth was 81%. The highest success rate was for transplantation of premolars to the maxillary incisor region (100%). Complications at surgery such as difficult extraction, deviant root anatomy, or damaged root periodontium affected the outcome. During growth, a successful transplant preserves alveolar bone.