Differential production of adrenal steroids by purified cells of the human adrenal cortex is relative rather than absolute

OBJECTIVES: The adrenal cortex produces aldosterone, cortisol and androgens in response to ACTH and angiotensin II. To define the differential response of morphologically distinct cells of the adrenal cortex, we examined the phenotypical and functional characteristics of human adrenocortical cells. RESULTS: Tumour growth factor-beta receptor-1 (TGFbeta-R1) and CYP-11 were found to be expressed predominantly in the zona fasciculata, whereas human leukocyte antigen (HLA-DR) and CYP-17 were localised to the zona reticularis. The angiotensin II receptor, AT-1, was found to be predominantly expressed in the zona glomerulosa. Adrenocortical cells, separated by density, yielded two distinct fractions which displayed differential growth patterns. Lipid-rich cells of fraction I expressed TGFbeta-R1 and produced significantly more cortisol relative to androstenedione than unseparated or fraction II cells, whereas lipid-poor cells of fraction II expressed HLA-DR and produced more androstenedione relative to cortisol in the presence of ACTH. Aldosterone production by fraction II was significantly greater than fraction I or unseparated cells. TGFbeta-R1-positive fasciculata-type cells separated into fraction I and HLA-DR-positive cells consistent with reticularis cells separated into fraction II. Aldosterone-producing cells indicative of glomerulosa cells separated into fraction II. CONCLUSIONS: Our findings are consistent with the concept that all adrenocortical cells are capable of producing a range of steroids, but the relative production of cortisol, androgen and aldosterone differs.     

MC4R dimerization in the paraventricular nucleus and GHSR/MC3R heterodimerization in the arcuate nucleus: is there relevance for body weight regulation?

The worldwide obesity epidemic is increasing, yet at this time, no long-acting and specific pharmaceutical therapies are available. Peripheral hormonal signals communicate metabolic status to the hypothalamus by activating their corresponding receptors in the arcuate nucleus (ARC). In this brain region, a variety of G protein-coupled receptors (GPCRs) are expressed that are potentially involved in weight regulation, but so far, the detailed function of most hypothalamic GPCRs is only partially understood. An important and underappreciated feature of GPCRs is the capacity for regulation via di- and heterodimerization. Increasing evidence implicates that heterodimerization of GPCRs results in profound functional consequences. Recently, we could demonstrate that interaction of the melanocortin 3 receptor (MC3R) and the growth hormone secretagogue receptor (GHSR)-1a results in a modulation of function in both receptors. Although the physiological role of GPCR-GPCR interaction in the hypothalamus is yet to be elucidated, this concept promises new avenues for investigation and understanding of hypothalamic functions dependent on GPCR signaling. Since GPCRs are important targets for drugs to combat many diseases, identification of heterodimers may be a prerequisite for highly specific drugs. Therefore, a detailed understanding of the mechanisms and their involvement in weight regulation is necessary. Fundamental to this understanding is the interplay of GPCR-GPCR in the hypothalamic nuclei in energy metabolism. In this review, we summarize the current knowledge on melanocortin receptors and GHSR-1a in hypothalamic weight regulation, especially as they pertain to possible drug targets. Furthermore, we include available evidence for the participation and significance of GPCR dimerization.     

Semantic contributions to immediate serial recall: Evidence from two contrasting aphasic individuals

This paper examines the effect of semantic variables on serial recall in two contrasting aphasic cases and a group of controls. Experiment 1 manipulates word imageability and Experiment 2 manipulates semantic similarity. Controls not only showed better recall of imageable/semantically grouped lists, but under some conditions they also produced proportionately fewer phonological errors. These findings suggest that increasing the effectiveness of lexical/semantic support reduces reliance on phonological support. Consistent with this proposal, case TV, whose phonological impairment should increase his reliance on lexical/semantic support, produced abnormally low rates of phonological errors under some conditions. Conversely, case NP, who had a lexical/semantic impairment, produced abnormally high rates of phonological errors under some conditions. Analysis of serial recall curves in both aphasics and controls support the hypothesis that phonological processes are particularly critical for the recall of list-final items. However, there was no evidence that semantic support is especially crucial for list-initial recall. Controls did not exhibit stronger effects of semantic variables at list-initial position. Case NP (lexical/semantic impairment) performed disproportionately poorly on these items, but only under certain conditions.     

Improved performance of SPECT-CT In-111 capromab pendetide by correlation with diffusion-weighted magnetic resonance imaging for identifying metastatic pelvic lymphadenopathy in prostate cancer

Purpose

To preliminarily evaluate the potential for an improvement in diagnostic performance by a combined interpretation of In-111 capromab pendetide single photon emission computed tomography (SPECT) including computed tomography (CT) image fusion with magnetic resonance diffusion-weighted imaging (MR-DWI) for identifying prostate cancer in pelvic lymph nodes thru correlation with histopathology.

Materials and methods

This institutional approved, retrospective study identified patients with available histopathology of lymph nodes removed at the time of radical prostatectomy and who had undergone staging with In-111 capromab pendetide SPECT-CT and/or pelvic MRI (including DWI). The performance of In-111 capromab pendetide SPECT for identifying malignant lymph nodes was assessed. Subsequently, a combined reading of In-111 capromab pendetide SPECT and prostate MRI with DWI was performed and the performance assessed.

Results

18 patients underwent In-111 capromab pendetide SPECT-CT. Of these, 12 patients had also undergone imaging with MR-DWI. In-111 capromab pendetide SPECT-CT had a sensitivity of 40.0 % and specificity of 96.7 % for identification of malignant lymph nodes. However, In-111 capromab pendetide SPECT-CT combined with MRI with DWI had a sensitivity of 88.9 % and specificity of 98.5 %.

Conclusions

The addition of MR-DWI to the interpretation of In-111 capromab pendetide SPECT-CT may increase the sensitivity for detecting malignant lymph nodes in prostate cancer. Future prospective evaluation of combined In-111 capromab pendetide SPECT-CT and MR-DWI is indicated and may improve clinical evaluation of nodal disease in prostate cancer.     

Das weltweite Medizinernetzwerk Aufklärung gegen Tabak – Ehrenamtliche Prävention made in Germany

Smoking is the leading preventable cause of premature death in Germany. The network “Education Against Tobacco” (EAT) is an initiative that was founded in Germany in 2012, in which more than 3500 medical students and physicians engage in volunteer work in about 80 medical faculties in 14 countries. In this article, the concept, activities, objectives and associated research studies oft he EAT initiative are introduced.On the school level, the initiative addresses 10- to 15-year-old secondary school students. In addition to a multimodal approach, school visits use modern media such as facemorphing apps, which are not only used by students (45,000 per year in 14 countries), but by a total of over 500,000 other people as well. The effectiveness of the school-based intervention is currently being investigated in randomised long-term studies with 20,000 adolescents in Germany. A first long-term study demonstrated evidence of a protective effect regarding the onset of smoking, especially among female students, students having a low level of education and students with a migratory background.The programme educates several hundred prospective physicians at 13 (of 28 participating) German medical faculties each year in science-based elective courses for the well-established smoking cessation counselling of patients and sensitises them to the tobacco epidemic. The approved members engage in dialogue with local members of the German house of representatives as “Ärzteverband Tabakprävention”.EAT motivates the prospective generation of physicians, initially through prevention in school settings, to face the challenge of national tobacco control at the university and federal level.     

Targeted postoperative care improves discharge outcome after hip or knee arthroplasty

OBJECTIVE: To determine whether targeted postoperative care, based on preoperative risk assessment, can increase the number of patients who are discharged home directly from acute care after elective hip or knee arthroplasty. DESIGN: Quasiexperimental with historical control. SETTING: A public university teaching hospital. PARTICIPANTS: One hundred patients who had an elective hip or knee arthroplasty. INTERVENTIONS: Between January and July 2001, 50 patients had their risk of discharge to extended inpatient rehabilitation assessed preoperatively with a newly developed Risk Assessment and Prediction Tool (RAPT). Postoperative management was targeted on the basis of the identified level of risk. Results were compared with those of a similar group of 50 patients treated between January and July 2000. MAIN OUTCOME MEASURES: Discharge destination, length of stay (LOS), and readmission rates. RESULTS: The percentage of patients discharged directly home increased significantly, from 34% during 2000 to 64% in 2001 (P=.002), with no increase in readmission rates in the 12 months postdischarge. In addition, the mean acute hospital LOS decreased by 1.1 days to 7.5 days in 2001 (P=.02). CONCLUSIONS: Use of the RAPT and targeted postoperative care resulted in more patients being discharged directly home after hip or knee arthroplasty while hospital LOS further decreased.