Glucocorticoid regulation of alkaline phosphatase in the osteoblastic osteosarcoma cell line ROS 17/2.8

Dexamethasone increased alkaline phosphatase levels up to 7-fold in the osteoblast-like rat osteosarcoma cell line ROS 17/2.8. This effect was associated with reduced cell growth and took place over several days in culture. The increase in enzyme activity was dose dependent, (half-maximum near 1 nM, with a hormone specificity suggesting glucocorticoid receptor mediation). Dexamethasone also increased enzyme activity in ROS 2/3 cells, but not in two nonosteoblastic osteosarcoma cell lines, indicating that among these cell lines, the effect is specific for osteoblast-like cells. Moreover, enzyme activity in both control and dexamethasone-treated cells correlated directly with levels of radioimmunoassayable bone-type isoenzyme. Increases in alkaline phosphatase activity in response to dexamethasone were detectable after about 5 h and were inhibited by both actinomycin D and cycloheximide. Thus glucocorticoids appear to increase de novo enzyme synthesis in ROS 17/2.8 cells. Finally, the cAMP-elevating agents PTH, isoproterenol, and 8-bromo-cAMP, which were previously shown to reduce alkaline phosphatase activity in osteoblast-like cells, antagonized the effects of dexamethasone. Moreover, in the presence of dexamethasone, lower concentrations of these agents were required for inhibitory effects on alkaline phosphatase.     

Psychological Adaptation to Serious Illness: A Qualitative Study of Culturally Diverse Patients With Advanced Chronic Kidney Disease

ContextPsychological distress is associated with adverse health outcomes in serious illness and magnified among patients of low socioeconomic status. Aspects of one's culture, such as religion and spirituality, can influence these patients' coping response to distress. Advanced chronic kidney disease (CKD) is a serious illness that disproportionately affects patients of low socioeconomic status, but a theory-based understanding of this group's lived experience of CKD is lacking.ObjectivesWe explored the cognitions, emotions, and coping behaviors of patients with CKD with emphasis on those of low socioeconomic status. We further inquired into any influences of religion or spirituality.MethodsWe interviewed 50 English-speaking or Spanish-speaking adults with advanced CKD from three medical centers in Nashville, Tennessee. Analyses occurred with isolation of themes; development of a coding system; and creation of a conceptual framework using an inductive-deductive approach.ResultsMedian age was 65 years; median annual income was $17,500 per year; and 48% of participants had not progressed beyond high school. Key beliefs (awareness of mortality and lack of control) influenced patients' emotions (existential distress in the form of death anxiety, prognostic uncertainty, and hopelessness) and coping behaviors (acceptance, avoidance, emotion regulation via spirituality, and seeking social support via a religious community).ConclusionIndividuals with advanced CKD and low socioeconomic status lack control over disease progression, experience death anxiety and existential distress, and emphasize spirituality to cope. Our study identifies novel components for a psychotherapeutic intervention for patients with advanced CKD at high risk for adverse health outcomes.     

Benchmarking Various Radiomic Toolkit Features While Applying the Image Biomarker Standardization Initiative toward Clinical Translation of Radiomic Analysis

Journal of Digital Imaging - The image biomarkers standardization initiative (IBSI) was formed to address the standardization of extraction of quantifiable imaging metrics. Despite its effort,...     

Novel CD3Z and CD3E Deficiency in Two Unrelated Females

Journal of Clinical Immunology -     

The long-term consequence of salivary contamination at various stages of adhesive application and clinically feasible remedies to decontaminate

Clinical Oral Investigations - To analyse the bond quality in dentine post-ageing after salivary contamination and decontamination at different stages of dental adhesive application. A total of...     

Recurrent hyperhemolytic transfusion reaction in myelodysplastic syndrome- A case based approach

We present here a case report of a 27 year old female, with myelodysplatic syndrome suspected to have recurrent hyperhemolytic transfusion reactions (HHTR). Patient was transfusion dependent for ten years and was transfused with leukodepleted and irradiated Packed Red Blood Cells (PRBC). She presented with signs and symptoms of acute intravascular hemolysis, deranged coagulation profile with post transfusion Hb lower than baseline. Post transfusion workup was uneventful. She was managed conservatively with fluid support and methylprednisolone initially. After few uneventful transfusions, patient developed second episode of HHTR with compatible unit.Immunophenotype favored an inflammatory response possibly induced by monocytic lineage. As transfusion dependent, the patient required methylprednisolone as premedication and all subsequent transfusions were uneventful.     

Orthopaedic Surgeons Receive the Most Industry Payments to Physicians but Large Disparities are Seen in Sunshine Act Data

Background

Industry payments made to physicians by drug and device manufacturers or group purchasing organizations are now reported to the Centers for Medicare and Medicaid Services (CMS) as a part of the Physician Payments Sunshine Act. Initial reports from the program show that orthopaedic surgeons lead all physician specialties in total and average industry payments. However, before further discussion of these payments and their implications can take place, it remains to be seen whether these figures are a true reflection of the field of orthopaedic surgery in general, rather than the result of a few outlier physicians in the field. In addition, the nature and sources of these funds should be determined to better inform the national dialogue surrounding these payments.

Questions/Purposes

We asked: (1) How do industry payments to orthopaedic surgeons compare with payments to physicians and surgeons in other fields, in terms of median payments and the Gini index of disparity? (2) How much do payments to the highest-receiving orthopaedic surgeons contribute to total payments? (3) What kind of industry payments are orthopaedic surgeons receiving? (4) How much do the highest-paying manufacturers contribute to total payments to orthopaedic surgeons?

Materials and Methods

We reviewed the most recent version of the CMS Sunshine Act Open Payments database released on December 19, 2014, containing data on payments made between August 1, 2013 and December 31, 2013. Data on total payments to individual physicians, physician specialty, the types of payments made, and the manufacturers making payments were reviewed. The Gini index of statistical dispersion was calculated for payments made to orthopaedic surgeons and compared with payments made to physicians and surgeons in all other medical specialties. A Gini index of 0 indicates complete equality of payments to everyone in the population, whereas an index of 1 indicates complete inequality, or all income going to one individual.

Results

A total of 15,376 orthopaedic surgeons receiving payments during the 5-month period were identified, accounting for USD 109,846,482. The median payment to orthopaedic surgeons receiving payments was USD 121 (interquartile range, USD 34–619). The top 10% of orthopaedic surgeons receiving payments (1538 surgeons) received at least USD 4160 and accounted for 95% of total payments. Royalties and patent licenses accounted for 69% of all industry payments to orthopaedic surgeons.

Conclusions

Even as a relatively small specialty, orthopaedic surgeons received substantial payments from industry (more than USD 110 million) during the 5-month study period. Whether there is a true return of value from these payments remains to be seen; however, future ethical and policy discussions regarding industry payments to orthopaedic surgeons should take into account the large disparities in payments that are present and also the nature of the payments being made. It is possible that patients and policymakers may view industry payments to orthopaedic surgeons more positively in light of these new findings.

Level of Evidence

Level III, Economic and Decision Analysis.