Context: Two reports suggested that vitamin D2 is less effective than vitamin D3 in maintaining vitamin D status.
Objective: Our objective was to determine whether vitamin D2 was less effective than ...vitamin D3 in maintaining serum 25-hydroxyvitamin D levels or increased the catabolism of 25-hydroxyvitamin D3.
Subjects and Design: This was a randomized, placebo-controlled, double-blinded study of healthy adults ages 18–84 yr who received placebo, 1000 IU vitamin D3, 1000 IU vitamin D2, or 500 IU vitamin D2 plus 500 IU vitamin D3 daily for 11 wk at the end of the winter.
Results: Sixty percent of the healthy adults were vitamin D deficient at the start of the study. The circulating levels of 25-hydroxyvitamin D (mean ± sd) increased to the same extent in the groups that received 1000 IU daily as vitamin D2 (baseline 16.9 ± 10.5 ng/ml; 11 wk 26.8 ± 9.6 ng/ml), vitamin D3 (baseline 19.6 ± 11.1 ng/ml; 11 wk 28.9 ± 11.0 ng/ml), or a combination of 500 IU vitamin D2 and 500 IU vitamin D3 (baseline 20.2 ± 10.4 ng/ml; 11 wk 28.4 ± 7.7 ng/ml). The 25-hydroxyvitamin D3 levels did not change in the group that received 1000 IU vitamin D2 daily. The 1000 IU dose of vitamin D2 or vitamin D3 did not raise 25-hydroxyvitamin D levels in vitamin D-deficient subjects above 30 ng/ml.
Conclusion: A 1000 IU dose of vitamin D2 daily was as effective as 1000 IU vitamin D3 in maintaining serum 25-hydroxyvitamin D levels and did not negatively influence serum 25-hydroxyvitamin D3 levels. Therefore, vitamin D2 is equally as effective as vitamin D3 in maintaining 25-hydroxyvitamin D status.
The key nuclear export protein CRM1/XPO1 may represent a promising novel therapeutic target in human multiple myeloma (MM). Here we showed that chromosome region maintenance 1 (CRM1) is highly ...expressed in patients with MM, plasma cell leukemia cells and increased in patient cells resistant to bortezomib treatment. CRM1 expression also correlates with increased lytic bone and shorter survival. Importantly, CRM1 knockdown inhibits MM cell viability. Novel, oral, irreversible selective inhibitors of nuclear export (SINEs) targeting CRM1 (KPT-185, KPT-330) induce cytotoxicity against MM cells (ED50<200 nM), alone and cocultured with bone marrow stromal cells (BMSCs) or osteoclasts (OC). SINEs trigger nuclear accumulation of multiple CRM1 cargo tumor suppressor proteins followed by growth arrest and apoptosis in MM cells. They further block c-myc, Mcl-1, and nuclear factor κB (NF-κB) activity. SINEs induce proteasome-dependent CRM1 protein degradation; concurrently, they upregulate CRM1, p53-targeted, apoptosis-related, anti-inflammatory and stress-related gene transcripts in MM cells. In SCID mice with diffuse human MM bone lesions, SINEs show strong anti-MM activity, inhibit MM-induced bone lysis and prolong survival. Moreover, SINEs directly impair osteoclastogenesis and bone resorption via blockade of RANKL-induced NF-κB and NFATc1, with minimal impact on osteoblasts and BMSCs. These results support clinical development of SINE CRM1 antagonists to improve patient outcome in MM.
Aim: To determine outcomes of bleb excision and conjunctival advancement for leaking or hypotonous eyes after glaucoma filtering surgery. Methods: In a retrospective case series the medical records ...of all patients who underwent bleb excision and conjunctival advancement surgery for bleb leaks or hypotony (defined as IOP less than 6 mm Hg, associated with reduced vision) at the Jules Stein Eye Institute and the Yale University Eye Center between January 1993 and June 2002 were reviewed. Only patients with more than 6 months of follow up were included. Complete success was defined as resolution of the pre-existing leak or hypotony, with maintenance of IOP ⩾6 and ⩽21 mm Hg, in the absence of further glaucoma surgery and without any glaucoma medication. Qualified success met the above criteria with or without the use of glaucoma medications. Success rates were analysed with Kaplan-Meier survival curves. Results: 49 eyes were included in the study; 13 eyes had overt bleb leaks, 27 eyes had hypotony. Nineteen patients underwent resuturing of sclera and/or placement of a pericardial graft in addition to bleb excision and conjunctival advancement. Mean preoperative IOP increased from 3.2 (SD 2.4) mm Hg (range 0–10 mm Hg) to 13.8 (4.8) mm Hg (range 6–29 mm Hg) at last follow up (p<0.0001). Mean preoperative visual acuity improved from 0.6 (0.3) logMAR (range 0–2) to 0.3 (0.3) logMAR (range 0–2) at final follow up (p<0.0001). 16 eyes (40%) were classified as complete success and 17 additional eyes achieved qualified success, for a total of 33 eyes (83%) achieving at least qualified success. There was no significant difference in the rate of complete success (p = 0.95) or qualified success (p = 0.88) between the group of patients who underwent bleb excision and conjunctival advancement alone versus those who also had resuturing of sclera and/or placement of a pericardial graft. Failures included three eyes that had persistent hypotony without leak, requiring additional bleb revision, and four with uncontrolled IOP, two of whom underwent additional glaucoma surgery. Conclusion: Bleb excision with conjunctival advancement is a successful procedure for bleb repair. This technique provides successful resolution of leaks and hypotony, maintains glaucoma control with or without medication, and preserves vision with minimal postoperative complications in a majority of eyes.
To validate a score based on clinical symptoms and signs for the identification of group A Streptococcus (GAS) infection in general practice patients with score throat.
A single throat swab was used ...as the gold standard for diagnosing GAS infection. Clinical information was recorded by experienced family physicians on standardized encounter forms. Score criteria were identified by means of logistic regression modelling of data from patients enrolled in the first half of the study. The score was then validated among the remaining patients.
University-affiliated family medicine centre in Toronto.
A total of 521 patients aged 3 to 76 years presenting with a new upper respiratory tract infection from December 1995 to February 1997.
Sensitivity, specificity and likelihood ratios for identification of GAS infection with the score approach compared with throat culture. Proportion of patients prescribed antibiotics, throat culture use, and sensitivity and specificity with usual physician care and with score-based recommendations were compared.
A score was developed ranging in value from 0 to 4. The sensitivity of the score for identifying GAS infection was 83.1%, compared with 69.4% for usual physician care (p = 0.06); the specificity values of the 2 approaches were similar. Among patients aged 3 to 14 years, the sensitivity of the score approach was higher than that of usual physician care (96.9% v. 70.6%) (p < 0.05). The proportion of patients receiving initial antibiotic prescriptions would have been reduced 48% by following score-based recommendations compared with observed physician prescribing (p < 0.001), without any increase in throat culture use.
An age-appropriate sore throat score identified GAS infection in children and adults with sore throat better than usual care by family physicians, with significant reductions in unnecessary prescribing of antibiotics. A randomized trial comparing the 2 approaches is recommended to determine the ability of the score approach to reduce unnecessary prescribing of antibiotics during routine clinical encounters.
Objectives/Hypothesis
Parotid gland calcifications can be incidental findings on computed tomography (CT) and have been reported to be associated with chronic inflammatory conditions. Associations ...between parotid gland calcification and other common medical conditions have not been reported.
Methods
Following institutional review board approval, 1,571 patients who underwent noncontrast head CT with 1.25‐mm slice thickness on a 64‐detector row CT between January 2011 and July 2011 were retrospectively reviewed for parotid gland calcifications. Medical records were reviewed for chronic kidney disease, alcoholism, autoimmune conditions, endocrine disorders, elevated alkaline phosphatase, and HIV (human immunodeficiency virus) status. Statistical analyses were performed using Fisher's exact test and multiple logistic regression.
Results
Sixty‐three of 1,571 (4%) patients had parotid gland calcifications. Significant associations were observed between parotid gland calcifications and HIV infection (P = 0.002), chronic kidney disease (P < 0.0001), alcoholism (P < 0.0001), elevated alkaline phosphatase (P = 0.003), and autoimmune disease (P = 0.02).
Conclusion
Parotid gland calcifications were associated with HIV, alcoholism, chronic kidney disease, autoimmune disease, and elevated alkaline phosphatase.
Level of Evidence
4. Laryngoscope, 125:1360–1365, 2015
Three studies demonstrate that morally praiseworthy behavior can signal negative information about an agent’s character. In particular, consequentialist decisions such as sacrificing one life to save ...an even greater number of lives can lead to unfavorable character evaluations, even when they are viewed as the preferred course of action. In Study 1, throwing a dying man overboard to prevent a lifeboat from sinking was perceived as the morally correct course of action, but led to negative aspersions about the motivations and personal character of individuals who carried out such an act. In Studies 2 and 3, a hospital administrator who decided not to fund an expensive operation to save a child (instead buying needed hospital equipment) was seen as making a pragmatic and morally praiseworthy decision, but also as deficient in empathy and moral character.
Public outrage is often triggered by “immaterially” harmful acts (i.e., acts with relatively negligible consequences). A well-known example involves corporate salaries and perks: they generate public ...outrage yet their financial cost is relatively minor. The present research explains this paradox by appealing to a person-centered approach to moral judgment. Strong moral reactions can occur when relatively harmless acts provide highly diagnostic information about moral character. Studies 1a and 1b first demonstrate dissociation between moral evaluations of persons and their actions—although violence toward a human was viewed as a more blameworthy act than violence toward an animal, the latter was viewed as more revealing of bad moral character. Study 2 then shows that person-centered cues directly influence moral judgments—participants preferred to hire a more expensive CEO when the alternative candidate requested a frivolous perk as part of his compensation package, an effect mediated by the informativeness of his request.
► We examined if moral evaluations of persons can be dissociated from evaluations of specific acts. ► Causing harm to a human was viewed as a worse act than causing harm to an animal. ► Causing harm to a human was viewed as less diagnostic of character than causing harm to an animal. ► Informative acts also directly influenced moral judgments and decisions. ► Participants avoided hiring a CEO who requested a frivolous compensation package.
Trochlear calcification is frequently seen on CT scans that include the orbits, but prior studies linking this finding to diabetes mellitus were based on selected populations by using relatively ...thick sections. We assessed the relationship between trochlear calcification and diabetes mellitus and other chronic medical conditions in an unrestricted population by using thin-section CT.
Noncontrast head CT studies performed consecutively on 1000 patients between January and February 2011 were retrospectively reviewed for the presence of trochlear calcifications. Axial 1.25-mm-thick images acquired by 64-detector row CT were reviewed. Medical records were reviewed for chronic medical conditions, including diabetes mellitus, chronic kidney disease, alcoholism, autoimmune conditions, endocrine disorders, serum calcium and alkaline phosphatase levels, and HIV status. Motion-limited studies and patients with limited clinical data were excluded. Statistical analyses were performed by using the Fisher exact test.
Thirty-two patients were excluded from analysis. Of the remaining 968 patients, 128 had trochlear calcification (13%). No significant association was observed between diabetes mellitus and trochlear calcifications in patients of any age (P = .40). There was no significant correlation between trochlear calcifications and chronic kidney disease, alcoholism, endocrine disorders, or HIV infection. Statistically significant associations among trochlear calcification, autoimmune conditions, and elevated alkaline phosphatase levels were observed (P < .0001 and P < .0001, respectively).
On the basis of a large unrestricted population with thin-section CT imaging of the orbit, no significant association was observed between trochlear calcifications and diabetes mellitus. A statistically significant association was observed between trochlear calcification and autoimmune disease and elevated alkaline phosphatase levels.
To assess the sagittal orientation of the cervical and thoracolumbar spine, 38 adolescents with idiopathic scoliosis were studied. The C7 plumb line and Cobb angles from C2-6, T1-12, and L1-S1 were ...measured on preoperative films. Lateral radiographs with > 1-year follow-up after surgical correction were available for the same measurements in 28 patients. The preoperative curve from C2-6 was 6 +/- 11 degrees of kyphosis. There was a significant correlation between the loss of thoracic kyphosis and the development of cervical kyphosis for the entire group preoperatively (p = 0.009). Postoperatively, cervical kyphosis increased to 11 +/- 9 degrees at 1-year follow-up (p = 0.05). There was no progression of cervical kyphosis in patients with "thoracic hypokyphosis" (kyphosis < 20 degrees). Cervical kyphosis increased in patients with "normal" thoracic kyphosis (20-40 degrees) and in patients with hyperkyphosis (kyphosis > 40 degrees) after surgery, despite preservation of thoracolumbar sagittal contour. There were no significant differences between the sagittal contour of patients treated with Cotrel-Dubousset or Harrington instrumentation.
Many tissues express thyroid hormone metabolizing deiodinases that both activate and inactivate thyroid hormones through conversion processes. Many believe that the primary role of thyroid hormone ...deiodinases is the activation of the prohormone thyroxine (T(4)) to the active hormone triiodothyronine because athyreotic humans can be treated with T(4) alone. In our hands a nonspecific deiodinase inhibitor (iopanoic acid IOP) decreased cutaneous cell proliferation in vitro, so we hypothesized that topical IOP would inhibit epidermal proliferation in vivo.
IOP was applied topically to mice. Treatments were applied daily for 1 week. Skin biopsies were either stained for 5-bromo-2-deoxyuridine or flash-frozen to assay for deiodinase activity.
Topical IOP resulted in a dose-dependent increase in epidermal proliferation. Assay revealed significant inactivating type 3 deiodinase (Dio3) activity in the epidermis but little or no activating (Dio1 or Dio2) activity. Dio3 activity was decreased 44%±21% in epidermis from mice treated with low-dose IOP and 80%±4% in epidermis from mice treated with high-dose IOP (p<0.001).
We hypothesize that keratinocytes express Dio3 in vivo to maintain cutaneous health and prevent the skin from becoming hyperproliferative. Our data support the developing recognition that the primary role of thyroid hormone deiodinases in some tissues may be the degradation of thyroid hormone to protect the tissue against thyrotoxicosis.
PDF
