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Biomedical subjects

Glenn D Braunstein

Publications and source records attributed to Glenn D Braunstein.

At least 19 recordsLinked to original sources
PubMed2006

Antitumor activity of suberoylanilide hydroxamic acid against thyroid cancer cell lines in vitro and in vivo.

PURPOSE: The histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), has multiple antitumor effects against a variety of human cancers. EXPERIMENTAL DESIGN: We treated several anaplastic and papillary thyroid cancer cell lines with SAHA to determine if it could inhibit the growth of these cells in vitro and in vivo. RESULTS: SAHA effectively inhibited 50% clonal growth of the anaplastic thyroid cancer cell lines, ARO and FRO, and the papillary thyroid cancer cell line, BHP 7-13, at 1.3x10(-7) to 5x10(-7) mol/L, doses that are achievable in patients. In concert with growth inhibition, SAHA down-regulated the expression of cyclin D1 and up-regulated levels of p21WAF1. Annexin V and cleavage of poly(ADP)ribose polymerase were both increased by exposure of the thyroid cancer cells to SAHA. Expression of the death receptor 5 (DR5) gene was also increased by SAHA, but the combination of the DR5 ligand, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), with SAHA had little effect compared with SAHA alone. Of note, the combination of paclitaxel, doxorubicin, or paraplatin with SAHA enhanced cell killing of the thyroid cancer cells. In addition, murine studies showed that SAHA administered daily by i.p. injection at 100 mg/kg inhibited the growth of human thyroid tumor cells. CONCLUSION: Our data indicate that SAHA is a plausible adjuvant therapy for thyroid cancers.

Animals↗
PubMed2006

Thyroiditis.

Thyroiditis is an inflammation of the thyroid gland that may be painful and tender when caused by infection, radiation, or trauma, or painless when caused by autoimmune conditions, medications, or an idiopathic fibrotic process. The most common forms are Hashimoto's disease, subacute granulomatous thyroiditis, postpartum thyroiditis, subacute lymphocytic thyroiditis, and drug-induced thyroiditis (caused by amiodarone, interferon-alfa, interleukin-2, or lithium). Patients may have euthyroidism, hyperthyroidism, or hypothyroidism, or may evolve from one condition to another over time. Diagnosis is by clinical context and findings, including the presence or absence of pain, tenderness, and autoantibodies. In addition, the degree of radioactive iodine uptake by the gland is reduced in most patients with viral, radiation-induced, traumatic, autoimmune, or drug-induced inflammation of the thyroid. Treatment primarily is directed at symptomatic relief of thyroid pain and tenderness, if present, and restoration of euthyroidism.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Androgen insufficiency in women.

Androgens are directly secreted by the ovaries and adrenals in women, and androgen precursors from these glands are converted in a variety of peripheral tissues into androgens. The major androgen in women is testosterone, and its action in target tissues can be mediated through the androgen receptor or through the estrogen receptor after aromatization to estradiol. Low sexual desire that causes personal distress (or hypoactive sexual desire disorder [HSDD]) is the most common form of female sexual dysfunction, and androgen insufficiency is one cause of this problem. In addition to a low libido, the clinical construct of the female androgen insufficiency syndrome includes the presence of persistent, unexplained fatigue and a decreased sense of well-being. Although there is conflicting information about the relationship between serum testosterone concentrations and sexual desire, multiple randomized, double-blind, placebo-controlled treatment trials have demonstrated that testosterone improves libido significantly more than placebo. Doses that provide physiologic to slightly supraphysiologic serum free or bioavailable testosterone concentrations are safe and associated with only mild androgenic side effects of acne and hirsutism. Oral, but not parenteral or transdermal, testosterone may decrease high-density lipoprotein cholesterol. At present, no testosterone preparation has been approved by the FDA for the treatment of low sexual desire (HSDD), so all such therapy is considered to be off-label use at this time.

Androgens↗
PubMed2006

Phytoestrogens and lipoproteins in women.

OBJECTIVES: We undertook a study to evaluate relationships among blood phytoestrogen levels, lipoprotein levels, estrogen levels, and angiographically defined coronary artery disease in women. BACKGROUND: Evidence for a beneficial role and the potential mechanism(s) of plant estrogens (phytoestrogens) on blood lipoproteins in humans is controversial. METHODS: We evaluated 483 women enrolled in the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation with coronary risk factors undergoing coronary angiography for evaluation for suspected ischemia for blood phytoestrogen levels (daidzein and genistein), lipoprotein levels [total cholesterol, triglycerides, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol (HDL-C)], estrogen levels (estradiol, bioavailable estradiol, estrone), and angiographic coronary artery disease using core laboratories. RESULTS: Higher blood levels of the phytoestrogen daidzein were associated with lower triglycerides (P = 0.01), higher HDL-C (P = 0.05) levels, and a beneficial total cholesterol to HDL-C ratio (P = 0.02). This beneficial association was evident among the subgroup of women with low [<184 pmol/liter (<50 pg/ml)] blood estradiol levels, regardless of age and lipoprotein levels. The phytoestrogen associations with lipoproteins were incrementally related to the magnitude of daidzein level and independent of other lipoprotein modulators. There were no detectable relationships between the phytoestrogen levels and angiographic coronary artery disease. CONCLUSIONS: Higher blood phytoestrogen daidzein levels are associated with beneficial lipoprotein levels in women with low estrogen levels, possibly by an estrogen receptor mechanism. These results suggest a potential explanation for the variable lipoprotein results observed in prior randomized controlled trials and call for investigation regarding subgroups of subjects who may preferentially benefit from dietary intake of food products, such as soy.

Adult↗
PubMed2006

Obesity distribution and reproductive hormone levels in women: a report from the NHLBI-sponsored WISE Study.

PURPOSE: Relationships between body weight and disease are not straightforward. Central obesity appears to be a relatively greater cardiovascular risk factor than generalized obesity. The purpose of this study was to evaluate body mass index (BMI) and waist circumference and the association of obesity distribution with blood estrogen levels (estradiol, bioavailable estradiol, and estrone). METHODS: The study cohort consisted of 207 postmenopausal women enrolled in the Women's Ischemia Syndrome Evaluation (WISE) undergoing angiography for evaluation of suspected ischemia. RESULTS: Both BMI and waist circumference were positively associated with all three blood estrogen levels (p < 0.01), with the highest estrogen levels found in the obese women with large waists (p < 0.01). Results from regression analyses confirmed significant associations of BMI and waist circumference with the estrogen levels. CONCLUSIONS: These results demonstrate differing relationships between blood estrogen levels and obesity distribution in a cohort of postmenopausal women with chest pain undergoing coronary angiography. The differing levels by general and central obesity may help explain in part observed epidemiological relationships between obesity and disease.

Adult↗
PubMed2005

Safety and efficacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: a randomized, placebo-controlled trial.

BACKGROUND: Oophorectomy reduces serum testosterone levels. We studied the efficacy and safety of transdermal testosterone in treating hypoactive sexual desire disorder in surgically menopausal women. METHODS: A 24-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial was conducted in women (aged 24-70 years) who developed distressful low sexual desire after bilateral salpingo-oophorectomy and hysterectomy and who were receiving oral estrogen therapy. Women were randomized to receive placebo (n = 119) or testosterone patches in dosages of 150 microg/d (n = 107), 300 microg/d (n = 110), or 450 microg/d (n = 111) twice weekly for 24 weeks. Sexual desire and frequency of satisfying sexual activity were primary efficacy outcome measures. RESULTS: Of the 447 women randomized, 318 (71%) completed the trial. Compared with placebo, women receiving the 300-microg/d testosterone patch had significantly greater increases from baseline in sexual desire (67% vs 48%; P = .05) and in frequency of satisfying sexual activity (79% vs 43%; P = .049). The 150-microg/d group showed no evidence of a treatment effect. The 450-microg/d group also was not statistically different from the 300-microg/d or placebo groups. Marginally significant linear dose-response trends were observed for total satisfying sexual activity and sexual desire at 24 weeks (P = .06 and .06, respectively). Adverse events occurred with similar frequency in both groups; no serious safety concerns were observed. CONCLUSIONS: The 300-microg/d testosterone patch increased sexual desire and frequency of satisfying sexual activity and was well tolerated in women who developed hypoactive sexual desire disorder after surgical menopause.

Administration, Cutaneous↗
PubMed2005

The use of dehydroepiandrosterone therapy in clinical practice.

Dehydroepiandrosterone (DHEA) therapy is controversial due to sensationalized reports of epidemiologic studies and the over-the-counter availability of DHEA. Human clinical trials have investigated the potential efficacy of DHEA therapy in multiple conditions with resultant inconsistencies in findings. DHEA is unique compared with other adrenal steroids because of the fluctuation in serum levels found from birth into advancing age. The lower endogenous levels of DHEA and DHEA sulfate found in advancing age have been correlated with a myriad of health conditions. Also, some studies suggest gender-specific actions of endogenous and exogenous DHEA. We reviewed only pharmacokinetic studies and human clinical trials investigating the efficacy of DHEA therapy that were placebo-controlled as these provided the most reliable scientific basis for the evaluation of DHEA therapy. Pharmacodynamic studies suggest that doses of 30-50mg of oral DHEA may produce physiologic androgen levels, especially in women. These studies report a dose-dependent effect and lack of accumulation of serum androgen levels. Pharmacologic studies also reveal a gender-specific response to DHEA therapy such that testosterone levels are increased in women but not in men. Clinical trials suggest that 50mg of oral DHEA, but not <30mg, can increase serum androgen levels to within the physiologic range for young adults with primary and secondary adrenal insufficiency, possibly improve sexual function, improve mood and self-esteem, and decrease fatigue/exhaustion. Whereas DHEA replacement therapy may be effective in treating patients with adrenal insufficiency, human clinical trials investigating its efficacy in conditions such as systemic lupus erythematosus, HIV, Alzheimer disease, advancing age, male sexual dysfunction, perimenopausal symptoms, depression, and cardiovascular disease have not provided consistent findings.

Adrenal Insufficiency↗
PubMed2004

Meta-analysis: angiotensin-receptor blockers in chronic heart failure and high-risk acute myocardial infarction.

BACKGROUND: The role of angiotensin-receptor blockers (ARBs) in treating patients with chronic heart failure and high-risk acute myocardial infarction (MI) has been controversial, and recent clinical trials provide more information on this topic. PURPOSE: To quantify the effect of ARBs when compared with placebo (with and without background angiotensin-converting enzyme [ACE] inhibitors) and ACE inhibitors on all-cause mortality and heart failure hospitalizations in patients with chronic heart failure and high-risk acute MI. DATA SOURCES: Data from original research published through 13 November 2003. STUDY SELECTION: Predefined criteria were used to identify 24 trials. DATA EXTRACTION: 2 reviewers independently collected information on study characteristics and data on all-cause mortality and heart failure hospitalization. DATA SYNTHESIS: 24 trials involving 38 080 patients were included. Analysis of chronic heart failure trials revealed that 1) ARBs were associated with reduced all-cause mortality (odds ratio [OR], 0.83 [95% CI, 0.69 to 1.00]) and heart failure hospitalizations (OR, 0.64 [CI, 0.53 to 0.78]) as compared with placebo; 2) for ARBs versus ACE inhibitors, all-cause mortality (OR, 1.06 [CI, 0.90 to 1.26]) and heart failure hospitalization (OR, 0.95 [CI, 0.80 to 1.13]) did not differ; 3) and for combinations of ARBs plus ACE inhibitors versus ACE inhibitors alone, all-cause mortality was not reduced (OR, 0.97 [CI, 0.87 to 1.08]) but heart failure hospitalizations were reduced (OR, 0.77 [CI, 0.69 to 0.87]). For patients with high-risk acute MI, 2 randomized trials compared ARBs with ACE inhibitors but did not reveal differences in all-cause mortality or heart failure hospitalization. LIMITATIONS: Comparative economic data between ARBs and ACE inhibitors are lacking. CONCLUSIONS: Because ACE inhibitors and ARBs do not differ in efficacy for reducing all-cause mortality and heart failure hospitalizations in patients with chronic heart failure and in patients with high-risk acute MI, ARBs should be regarded as suitable alternatives to ACE inhibitors.

Angiotensin Receptor Antagonists↗
PubMed2004

Androgen replacement therapy in women.

OBJECTIVE: Review of literature with regard to androgen replacement therapy in women. DESIGN: Review of the MEDLINE database and references from articles. CONCLUSIONS: Androgens affect sexual function, bone health, muscle mass, body composition, mood, energy, and the sense of well-being. Androgen insufficiency clearly has been demonstrated in patients with hypopituitarism, adrenalectomy, oophorectomy, and in some women placed on oral estrogen therapy which increases sex hormone-binding globulin (SHBG) levels and lowers the free and bioavailable forms of T. Symptoms of androgen insufficiency in women may include a diminished sense of well-being, low mood, fatigue, and hypoactive sexual desire disorder with decreased libido, or decreased sexual receptivity and pleasure that causes a great deal of personal distress. The preponderance of evidence from clinical trials supports the correlation of decreased endogenous androgen levels with these symptoms and alleviation of many of the symptoms with the administration of T or, in some cases, DHEA. There are no Food and Drug Administration-approved androgen preparations on the market for treating androgen insufficiency in women. The safety profile of androgens in doses used for the treatment of hypoactive sexual desire disorder has been excellent with only mild acne and hirsutism being noted in a minority of patients.

Androgens↗
PubMed2004

Thyroid carcinoma arising from a sacrococcygeal mass: a malignant teratoma?

A 59-year-old African American male with a remote history of Graves' disease presented with a 13-cm sacrococcygeal mass that was resected. Pathologic examination revealed this to be papillary thyroid carcinoma with large areas of hemorrhage and necrosis. No other teratomatous elements were identified. The patient underwent extensive evaluation of the thyroid gland with ultrasound, computed tomography (CT) scan, and laboratory studies without any evidence of thyroid mass or malignancy. In addition, further evaluations with chest/abdominal/pelvic CT as well as a bone scan failed to reveal any evidence of metastatic disease. At 1-year follow-up, the patient has remained euthyroid and without evidence of recurrence. We believe that our patient may represent the first reported case of malignant transformation of mature thyroid tissue in a sacrococcygeal teratoma. The impact of his diagnosis on the decision-making for performing a total thyroidectomy is discussed.

Carcinoma, Papillary↗
PubMed2004

Determination of menopausal status in women: the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) Study.

PURPOSE: Accurate classification of menopausal status is important to epidemiological research evaluating the role of reproductive hormones in disease processes. Algorithms relying on repeat hormone assays are unfeasible in large epidemiological studies. This paper summarizes the development of the Women's Ischemia Syndrome Evaluation (WISE) Hormonal menopausal status algorithm for determining premenopausal, perimenopausal, and postmenopausal status using menstrual and reproductive history and reproductive hormone levels obtained at a single clinic visit. METHODS: The authors compared the accuracy of this algorithm with two currently used self-report algorithms: Menstrual, based only on months since last menstrual period, and Historical, which adds age and surgical history. RESULTS: The study population consisted of 515 women (329 clearly postmenopausal) enrolled in the WISE study who were undergoing coronary angiography for suspected ischemia. A subgroup of 186, not clearly postmenopausal, was classified by these three algorithms. Results were evaluated against individualized expert consensus classification. The Menstrual and Historical classifications differed significantly (p < 0.0001) from expert consensus, with 32%-26% discordant classifications, respectively. For the WISE Hormonal classification, discordance was 4%. CONCLUSIONS: The authors conclude that inaccurate classifications of menopausal status occur frequently in self-report algorithms. Use of the relatively simple WISE algorithm can improve the accuracy of menopausal status classification for epidemiological research.

Adult↗
PubMed2003

Management of the clinically inapparent adrenal mass ("incidentaloma").

The National Institutes of Health Consensus Development Program convened surgeons, endocrinologists, pathologists, biostatisticians, radiologists, oncologists, and other health care professionals, as well as members of the general public, to address the causes, prevalence, and natural history of clinically inapparent adrenal masses, or "incidentalomas"; the appropriate evaluation and treatment of such masses; and directions for future research. Improvements in abdominal imaging techniques have increased detection of adrenal incidentalomas, and because the prevalence of these masses increases with age, appropriate management of adrenal tumors will be a growing challenge in our aging society. To address six predetermined questions, the 12-member nonfederal, nonadvocate state-of-the-science panel heard presentations from 21 experts in adrenal incidentalomas and consulted a systematic review of medical literature on the topic provided by the Agency for Healthcare Research and Quality and an extensive bibliography developed by the National Library of Medicine. The panel recommended a 1-mg dexamethasone suppression test and measurement of plasma-free metanephrines for all patients with an adrenal incidentaloma; additional measurement of serum potassium and plasma aldosterone concentration-plasma renin activity ratio for patients with hypertension; and surgery for patients with biochemical evidence of pheochromocytoma, patients with tumors greater than 6 cm, and patients with tumors greater than 4 cm who also meet other criteria. The panel also advocated a multidisciplinary approach to managing adrenal incidentalomas. The statement is an independent report of the panel and is not a policy statement of the National Institutes of Health or the federal government.

Adrenal Gland Neoplasms↗
PubMed2003

Hypoestrogenemia of hypothalamic origin and coronary artery disease in premenopausal women: a report from the NHLBI-sponsored WISE study.

OBJECTIVES: We sought to evaluate hypoestrogenemia of hypothalamic origin and its association with angiographic coronary artery disease (CAD) in premenopausal women. BACKGROUND: Coronary artery disease in premenopausal women appears to have a particularly poor prognosis. Primate animal data suggest that premenopausal CAD is strongly determined by psychosocial stress-induced central disruption of ovulatory cycling and resulting hypoestrogenemia. METHODS: We assessed reproductive hormone blood levels and angiographic CAD using core laboratories in 95 premenopausal women with coronary risk factors who were enrolled in the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation and were undergoing coronary angiography for evaluation for suspected ischemia. RESULTS: Premenopausal women with angiographic CAD (n = 13) had significantly lower estradiol, bioavailable estradiol, and follicle-stimulating hormone (FSH) (all p < 0.05) than women without angiographic CAD (n = 82), even after controlling for age. Hypoestrogenemia of hypothalamic origin, defined as estradiol <184 pmol/l (50 pg/ml), FSH <10 IU/l, and luteinizing hormone <10 IU/l, was significantly more prevalent among the women with CAD than those without CAD (9/13 [69%] vs. 24/82 [29%], respectively, p = 0.01). Hypoestrogenemia of hypothalamic origin was the most powerful predictor of angiographic CAD in a multivariate model (odds ratio [OR] 7.4 [confidence interval (CI) 1.7 to 33.3], p = 0.008). Anxiolytic/sedative/hypnotic and antidepressant medication use were independent predictors of hypoestrogenemia of hypothalamic origin in a multivariate model (OR 4.6 [CI 1.3 to 15.7], p = 0.02, OR 0.10 [CI 0.01 to 0.92], p = 0.04, respectively). CONCLUSIONS: Among premenopausal women undergoing coronary angiography for suspected myocardial ischemia, disruption of ovulatory cycling characterized by hypoestrogenemia of hypothalamic origin appears to be associated with angiographic CAD.

Adult↗
PubMed2003

Thyroid stunning.

Debates regarding thyroid stunning-a phenomenon whereby a diagnostic dose of radioiodine decreases uptake of a subsequent therapeutic dose by remnant thyroid tissue or by functioning metastases-have been fueled by inconsistent research findings. Quantitative studies evaluating radioiodine uptake and qualitative studies using visual observations both compare thyroid function on the diagnostic scan (DxSCAN) versus the posttreatment whole-body scan (RxWBS). The variability of findings may be the result of a lack of consensus in clinical nuclear medicine regarding many parameters of radioiodine usage including the need to obtain a pretreatment diagnostic scan, appropriate therapeutic dose, time between therapy dose administration and DxSCAN, and how successful ablation is measured. In the studies considered in this review, those that used (123)I rather than (131)I for DxSCAN, allowed less time to elapse between diagnostic and therapy dose, and more time between therapy dose and RxWBS (at least 1 week), did not observe stunning. However, groups that recognized stunning did not demonstrate any difference in outcomes (determined by successful first-time ablation). Whether stunning is a temporary phenomenon whereby stunned tissue eventually rejuvenates, or whether observed stunning actually constitutes "partial ablation," is yet to be delineated.

Dose-Response Relationship, Drug↗
PubMed2002

Cholesterol-lowering medication, cholesterol level, and reproductive hormones in women: the Women's Ischemia Syndrome Evaluation (WISE).

PURPOSE: Reproductive hormones such as estrogen, progesterone, and testosterone are synthesized from a common cholesterol precursor pathway. We hypothesized that use of statins and the resultant lower blood lipoprotein levels would be associated with lower reproductive hormone levels in women. We also sought to evaluate this association, independent of statin use, particularly among premenopausal women of childbearing age. METHODS: We enrolled 453 (114 pre-, 30 peri-, and 309 postmenopausal) women with coronary risk factors (mean [+/- SD] age, 58 +/- 13 years) who were undergoing coronary angiography for suspected ischemia at four academic medical centers. Blood lipoprotein levels (total cholesterol, triglycerides, low-density lipoprotein [LDL] cholesterol, high-density lipoprotein cholesterol) and serum reproductive hormone levels (estradiol, bioavailable estradiol, estrone, progesterone) were measured. RESULTS: Use of statins was associated with lower lipoprotein levels, but not lower reproductive hormone levels, in all women. Mean estradiol levels were not significantly lower among premenopausal women with very low LDL cholesterol levels compared with women with higher LDL cholesterol levels (estradiol: 71 +/- 52 pg/mL vs. 88 +/- 67 pg/mL, P = 0.32). CONCLUSION: Among women undergoing coronary angiography for suspected myocardial ischemia, the use of statins, or lower cholesterol levels, are not associated with significantly lower levels of reproductive hormones.

Adult↗
PubMed2002

Do subspecialists working outside of their specialty provide less efficient and lower-quality care to hospitalized patients than do primary care physicians?

BACKGROUND: Studies show that subspecialists can provide better quality care than primary care physicians when working within their subspecialty for patients with some medical conditions. However, many subspecialists care for patients outside of their chosen subspecialty. The present study compared the quality of care provided by subspecialists practicing outside of their specialty, general internists, and subspecialists practicing within their specialty. METHODS: The severity-adjusted mortality rate and the severity-adjusted length of stay were used as indexes of quality of care. Data from 5112 hospital admissions (301 different physicians) for community-acquired pneumonia, acute myocardial infarction, congestive heart failure, or upper gastrointestinal hemorrhage at 6 hospitals in the greater Cleveland, Ohio, area were used in this study. The data were severity adjusted with the CHOICE Severity of Illness System. RESULTS: Subspecialists working outside of their subspecialty cared for 25% of hospitalized patients. When comparing patients cared for by subspecialists practicing outside of their subspecialty, severity-adjusted lengths of stay were longer for patients with congestive heart failure (23% longer; 95% confidence interval [CI], 15%-32%), upper gastrointestinal hemorrhage (22% longer; 95% CI, 7%-39%), and community-acquired pneumonia (14% longer; 95% CI, 5%-24%) than for patients cared for by subspecialists practicing within their subspecialty. Patients also had a slightly higher hospital mortality rate when cared for by subspecialists practicing outside of their specialty than by subspecialists practicing within their subspecialty (mortality rate odds ratio, 1.46; P =.047). In addition, patients cared for by subspecialists practicing outside of their subspecialty had longer lengths of stay, and prolongations of stay were observed for patients with congestive heart failure (16% longer; 95% CI, 8%-26%), upper gastrointestinal hemorrhage (15% longer; 95% CI, 2%-30%), and community-acquired pneumonia (18% longer; 95% CI, 9%-28%) than patients cared for by general internists. CONCLUSIONS: Subspecialists commonly care for patients outside of their subspecialty, despite the fact that their patients may have longer lengths of stay than those cared for by subspecialists practicing within their specialty or by general internists. In addition, such patients may have slightly higher mortality rates than those cared for by subspecialists practicing within their subspecialty.

Aged↗