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Endocrine Discovery |
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 Top Endocrine Discovery Possible New Drug for...Fertility Revealed Through VoiceEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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In a cross-sectional echocardiographic study of 102 patients receiving cabergoline for endocrine disorders (cumulative dose 18–1718 mg) and 51 controls, there was no difference in mitral valve regurgitation between groups. Mitral valve tenting area was greater in the cabergoline group (P=0.03), but no patient had aortic or tricuspid valvular restriction. (Eur J Endocrinol [July 1, 2008] 159 (1):1)
Positive associations between depressive symptoms and incident type 2 diabetes, and conversely between treated type 2 diabetes and depressive symptoms were found in a prospective cohort study of 5201 persons followed for 4 years. (JAMA [June 18, 2008] 299 (23):2751)
Human herpes virus-8 (HHV-8) antibodies were found in 71 patients (88%) with ketosis-prone type 2 diabetes vs. 16 patients (15%) with nonketotic DM-2 and 40% of control participants in a cross-sectional study of sub-Saharan African patients. (JAMA [June 18, 2008] 299 (23):2770)
Intensive therapy to achieve normal HbA1C levels for 3.5 years increased mortality without a reduction in major cardiovascular events compared to standard glucose control in a randomized prospective study of 10,251 patients with type 2 diabetes. (N Engl J Med [June 12, 2008] 358 (24):2545)
Patients with type 2 diabetes randomized to standard or intensive glucose control (HbA1C 
6.5%) demonstrated a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily due to a decrease in nephropathy in a prospective study of 11,140 patients.
(N Engl J Med [June 12, 2008] 358 (24):2560)
In 1,791 U.S. veterans with type 2 diabetes, intensive blood glucose control to an HbA1C below 7% had no significant effect on cardiovascular disease reduction. (presented at the American Diabetes Association annual meeting and ENDO 08, June 2008)
In a phase II study of the multi-kinase inhibitor sorafenib in 30 patients with metastatic differentiated thyroid cancer, 90% of which were unresponsive to radioiodine, there was a partial response in 23% and stable disease in 53% of patients who were treated for 16 or more weeks, with acceptable toxicity. (J Clin Oncol [published electronically ahead of print June 9, 2008])
A health-related quality of life study among 2,445 youths diagnosed with type 1 or 2 diabetes found that a patient’s age, social environment, financial resources, treatment type, and disease severity all affect the daily management of diabetes. Youths with type 2 diabetes reported a lower quality of life than those with type 1, and adolescent girls reported a lower quality of life than adolescent boys. (Arch Pediatr Adolesc Med [July 2008] 162 (7):649)
Among 329 patients with diabetes and comorbid major depression, those who received nurse depression intervention had a reduced 5-year mean total medical cost of -$3,907 (95% CI -$15,454 less to $7,640 more) compared to usual care patients. (Diabetes Care [June 2008] 31 (6):1155)
Childhood socioeconomic position in women was a robust predictor of incident diabetes in a study of 5,913 adults. A cumulative risk effect was seen for childhood socioeconomic position and adult BMI as well. (Am J Pub Health [published electronically ahead of print June 12, 2008])
Low serum levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were associated with increased risk in all-cause and cardiovascular mortality compared to patients with higher serum vitamin D levels. (Arch Int Med [June 23, 2008] 168 (12):1340)
Evaluation of 36 tag SNPs across the CD36 gene in a population sample of 2,020 African-Americans found 5 SNPs associated with increased odds for the metabolic syndrome (MetS) [P=0.0027–0.03, OR=1.3–1.4); one SNP conferring protection against MetS (P=0.0012, OR=0.61, 95% CI: 0.46–0.82), increased high-density lipoprotein cholesterol (HDL-C) (P=0.00018) and decreased triglycerides (P=0.0059); and 15 additional SNPs associated with HDL-C (P=0.0028–0.044). (Human Molecular Genetics [June 1, 2008] 17 (11):1695)
A prospective cohort study of 1,001,391 postmenopausal women found that use of hormone replacement therapy increases the risk of gallbladder disease, with this risk slightly lower for those who use transdermal over oral therapy (relative risk: 1.17 vs. 1.74). (BMJ [published online July 10, 2008])
Modification of Krüppel-like transcription factor 5 (KLF5) by small ubiquitin-related modifier (SUMO) proteins functions as a molecular switch for fatty acid oxidation programs involving proliferator-activated receptor-
(PPAR-) and various co-regulators. This may represent a potential therapeutic strategy against metabolic syndrome.
(Nature Medicine [June 2008] 14 (6):656)
Placenta-induced hypoxia during mice embryogenesis led to the formation of giant osteoclasts through the signaling of leukemia inhibitory factor (LIF) and its receptor by Fos-related protein Fra-2, offering potential targets for treatment of syndromes associated with increased osteoclastogenesis such as osteoporosis, Paget’s disease, and multiple myeloma. (Nature [July 10, 2008] 454:221)[CrossRef]
Leptin infused into the mediobasal hypothalamus of rats inhibited white adipose tissue lipogenesis independently of signal transducer and activator of transcription-3 (STAT) signaling and suppressed the endocannabinoid anandamide in white adipose tissue, suggesting that increased endocannabinoid tone observed in obesity is linked to a failure of central leptin signaling to restrain peripheral endocannabinoids. (Nature Medicine [June 2008] 14 (6):667)
Maintenance of reduced body weight is associated with leptin-reversible changes in neural activities in response to visual food cues in the brainstem, culmen, parahippocampal gyrus, inferior and middle frontal gyri, middle temporal gyrus, and lingual gyrus, implying that the weight-reduced state is one of relative leptin deficiency. (J Clin Invest [July 1, 2008] 118 (7):2583)
In pancreatic 
cells, a glutamate autocrine feedback loop facilitating sufficient glucagon release was demonstrated.
(Cell Metabolism [June 4, 2008] 7 (6):545)
The crystal structure of the Vibrio parahaemolyticus sodium/galactose symporter (vSGLT) was characterized, providing possible insight into the rational design of SGLT-related drugs for the treatment of diabetes. (Science [published online July 3, 2008])
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Possible New Drug for Advanced Thyroid Cancer |
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TopEndocrine DiscoveryPossible New Drug for...Fertility Revealed Through VoiceEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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In an open-label, single-group, multi-center, phase 2 study, motesanib diphosphate (AMG 706), a novel angiogenic inhibitor, was given orally to 93 patients with progressive, locally advanced or metastatic, radioiodine-resistant differentiated thyroid cancer. While no complete response was observed, a partial response was seen in 14% of the patients. Additionally, stable disease was achieved in 67% of the patients, 35% of whom maintained this state for 24 weeks or longer. Side effects were few, including hypertension, fatigue, and weight loss.
"Currently for patients with metastatic differentiated thyroid cancer there’s only one approved treatment—a form of chemotherapy called doxorubin/adriamycin—and that hasn’t changed for 25 years," said lead author Steven Sherman, M.D., chairman of the Department of Endocrine Neoplasia and Hormonal Disorders at the University of Texas M. D. Anderson Cancer Center in Houston. "We’re bringing thyroid cancer treatment up to the same level and state-of-the-art that other common forms of cancer are experiencing."
To pinpoint which patients would fare better on the drug, the group performed molecular analysis on the tumors of 33 patients. Nearly twice as many patients who responded to the treatment had B-type Raf Kinase (BRAF) mutations compared with those patients who did not have the mutation, indicating that BRAF mutant tumors appear to be more sensitive to this drug.
"This is the first effort to correlate response with tumor genotype in this type of cancer," Dr. Sherman said, adding that other cancers such as lung and breast are further ahead in this form of screening. "This sort of personalized cancer therapy is likely to be where we’ll be 5–10 years from now."
Other thyroidologists hailed the drug as a step in the right direction for the field.
"It’s really the first salvo in the war on advanced thyroid cancer," said Gil Daniels, M.D., clinical director of the endocrine genetics program at the Massachusetts General Hospital Cancer Center in Boston. "Five years ago there was not a single clinical trial. Now three successful trials have been published with a few months and more are on the way. It’s really an important advance."
"There really isn’t much we had to offer these patients other than placing them on other clinical cancer trials. If there’s one tumor, we perform surgery or irradiate; and if it’s metastatic, we consider chemotherapy which has a modest response and high toxicity," said Bryan Haugen, M.D., endocrinology professor at University of Colorado Denver Anschutz Medical Campus, in Aurora. Motesanib, he said, is "no home run, but overall, the response was good. In the future it will probably be useful in combination with other therapies. Still, it’s a really exciting time." (N Engl J Med [July 3, 2008] 359 (1):31)
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Fertility Revealed Through Voice |
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TopEndocrine DiscoveryPossible New Drug for...Fertility Revealed Through VoiceEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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"The same hormones affecting the menstrual cycle and its tissues such as the endometrium also have comparable effects on the tissues of the larynx," said Pipitone, whose paper with Gallup was published in the February issue of Evolution and Human Behavior.
Evolution also plays a role. Dr. Gallup explained that our ancestors may have been forced to rely on voice more when the sun went down and they needed to decipher subtle tonal shifts in a person’s voice.
"Voice is a medium that conveys a lot of important biological information," he said. "Say you’ve had the experience of answering the phone only to discover you don’t know who it is. As soon as they talk, you immediately know if it’s male or female and if it’s an adult or child."
Pipitone and Gallup recorded the voices of 51 female undergraduates counting from 1 to 10 at four points in their menstrual cycles. These women were either naturally cycling or were using hormonal contraceptives. The duo then played the voice samples back to 34 male and 32 female undergraduates who were asked to rate the attractiveness of the voices.
The raters judged the voices as being more attractive as the females’ risk of conception, or more fertile time in their menstrual cycles, approached, indicating that these women are subconsciously sending subtle cues about their reproductive potential. Such variation was absent in women taking hormonal contraceptives.
"It elaborates on the idea that your hormones affect your voice and that people can pick up on these changes," said Susan Hughes, Ph.D, assistant psychology professor at Albright College, Reading, Pennsylvania, whose own studies have shown that voices can indicate body symmetry and shape, such as whether a women is hour-glass-shaped or a man is V-shaped, both indicators of one’s hormonal profile, good health, and genetic fitness.
Previous studies, Dr. Hughes conversely pointed, also show that women’s preference for certain male voices change throughout their menstrual cycle. "It works both ways," she said.
Dr. Gallup wryly suggested that this information may be useful for those in the dating pool. "It would suggest a distinction between a blind date, or date sight unseen, and a deaf date, or date sound unheard," he said. "Before you agree to a blind date it would probably be a good idea to afford yourself the opportunity to at least have a phone conversation with them first. Then you would be able to make a more informed choice about whether to date this person." (Evol Hum Behav [February 2008] 29:268)[CrossRef]
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Endocrine Practice |
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TopEndocrine DiscoveryPossible New Drug for...Fertility Revealed Through VoiceEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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A free, Spanish consumer guide for adults who have type 2 diabetes and need information comparing various oral medications for their illness, "Pastillas para la diabetes tipo 2," has been released by the Agency for Healthcare Research and Quality. This guide, as well as its English-language version, can be found online at http://effectivehealthcare.ahrq.gov.
The U.S. Food and Drug Administration is encouraged clinicians prescribing propylthiouracil to write out either the full established name, provide a proprietary name, or indicate the drug’s use rather than indicating "PTU" alone. Recently a pregnant hyperthyroid woman prescribed "PTU 50 mg" was mistakenly given Purinethol (mercaptopurine), spontaneously aborted her fetus, and died. For more information, see the August 11 edition of Drug Topics.
The U.S. Food and Drug Administration granted orphan drug status to DuoCort, a hydrocortisone dual-release oral tablet totreat adrenal insufficiency. The formulation is being tested in Phase II/II clinical trials in Europe in 5–mg and 20-mg doses in comparison to conventional three-times daily hydrocortisone therapy. For more info see: http://fdanews.com/newsletter/article?issueId=11738&articleId=108248 and www.duocort.com.
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Milestones in Endocrinology |
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TopEndocrine DiscoveryPossible New Drug for...Fertility Revealed Through VoiceEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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In the Journal 25 Years Ago |
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TopEndocrine DiscoveryPossible New Drug for...Fertility Revealed Through VoiceEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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"When the necessary facilities and expertise are available, we recommend total thyroidectomy for the treatment of differentiated thyroid cancer, followed by ablative 131I, at least in those patients with follicular andmixed tumors."
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Footnotes |
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