Adipokines as atherothrombotic risk factors in obese subjects: Associations with haemostatic markers and common carotid wall thickness.

BACKGROUND AND AIMS: Some crucial associations between obesity-related altered adipokine levels and the main factors of atherosclerotic, atherothrombotic processes are not fully known. We analysed the relationships of classic adipokines, namely leptin, resistin, adiponectin, tumour necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) with the markers of platelet activation, including mean platelet volume (MPV), platelet surface/soluble P-selectin, platelet-derived microparticles (PMPs), the parameters of coagulation abnormalities and common carotid intima-media thickness (IMT) in obese patients with or without atherosclerotic comorbidities in comparison to age- and sex-matched controls. METHODS AND RESULTS: We enrolled 154 obese individuals, including 98 suffering from atherosclerotic concomitant conditions, 56 free of atherosclerotic comorbidities and 62 healthy controls. Plasma levels of leptin, resistin, adiponectin, TNF-α, IL-6, soluble P-selectin, and plasminogen activator inhibitor-1 antigen (PAI-1 ag) were analysed by ELISA. Platelet surface P-selectin and PMPs were measured by flow cytometry. IMT was detected by ultrasonography. Adipokines were closely associated with markers of platelet hyperactivity, hypercoagulability, hypofibrinolysis and IMT. Significant independent associations were found between leptin and platelet count (p < 0.0001), MPV (p = 0.019), PMPs (p < 0.0001), fibrinogen (p = 0.001), factor VIII (FVIII) activity (p = 0.035); adiponectin and PAI-1 ag (p = 0.035); resistin and soluble P-selectin (p = 0.002); TNF-α and PAI-1 ag (p < 0.0001); and IL-6 and fibrinogen (p = 0.011). Finally, leptin (p = 0.0005), adiponectin (p = 0.019), IL-6 (p = 0.001), MPV (p = 0.0003), PMP (p = 0.008), and FVIII activity (p = 0.043) were independent predictors of IMT. CONCLUSION: Overall, we suggest that in obese subjects altered adipokine levels play a key role in common carotid atherosclerosis both directly and through haemostatic parameters.

Obesity as a risk factor for malignant melanoma and non-melanoma skin cancer.

The dramatic increases in incidence of both obesity and many cancers including skin cancer emphasize the need to better understand the pathophysiology of both conditions and their connections. Melanoma is considered the fastest growing cancer and rates of non-melanoma skin cancer have also increased over the last decade. The molecular mechanisms underlying the association between obesity and skin cancer are not clearly understood but emerging evidence points to changes in the tumor microenvironment including aberrant cell signaling and genomic instability in the chronic inflammatory state many obese individuals experience. This article reviews the literature linking obesity to melanoma and non-melanoma skin cancer.

Building a New Model of Care for Rapid Breast Radiotherapy Treatment Planning: Evaluation of the Advanced Practice Radiation Therapist in Cavity Delineation.

AIMS: Breast radiotherapy treatment is commonly managed by a multidisciplinary team to ensure optimal delivery of care. We sought a new model of care whereby a clinical specialist radiation therapist (CSRT) delineates the cavity target for whole breast radiotherapy treatment planning and the radiation oncologist validates the contour during final plan review. This study evaluated the radiation oncologist's acceptance of these contours and identified characteristics of cavities suitable for CSRT-directed contouring. MATERIALS AND METHODS: Following specialised breast oncology education and training by the radiation oncologist, the CSRT prospectively delineated cavities in 30 tangential breast radiotherapy cases and consulted the radiation oncologist in 'complex' cases but directed 'non-complex' cases for treatment planning. Changes to CSRT contours were evaluated using the conformity index. Breast density, time since surgery and cavity location, size and visualisation score [CVS: range 1 (no visible cavity) to 5 (homogenous cavity)] were captured. RESULTS: Of the 30 CSRT delineated cavities contours, the CSRT directed 20 (66.7%) cases for planning without radiation oncology review; 19 were accepted (without changes) by the radiation oncologist upon final plan review and one was changed by the radiation oncologist (conformity index = 0.93) for boost treatment and did not affect the tangential treatment plan. Ten (33.3%) cases, all CVS ≤ 3, were reviewed with the radiation oncologist before planning (conformity index = 0.88 ± 0.12). CVS was inversely correlated with breast density and cavity size (P < 0.01). CONCLUSIONS: The CSRT delineated cavities appropriate for clinical radiotherapy treatment planning in women with well-visualised cavities, whereas 'complex' cases with dense breast parenchyma, CVS ≤ 3, and/or cases needing boost radiotherapy treatment required review with the radiation oncologist before planning.

The effects of indoor and outdoor temperature on metabolic rate and adipose tissue - the Mississippi perspective on the obesity epidemic.

Global warming, primarily caused by emissions of too much carbon dioxide, and climate change is a reality. This will lead to more extreme weather events with heatwaves and flooding. Some studies propose an association between thermal exposures and the prevalence of obesity with an increasing trend towards time spent in the thermal comfort zone. Longterm exposure to the thermal comfort zone can lead to a reduction of brown adipose tissue activity with an impact on energy expenditure and thermogenesis. Reduced seasonal cold exposure in combination with reduced diet-induced thermogenesis by a highly palatable high-fat and high-sugar diet and reduced physical activity contribute to the prevalence of obesity and the metabolic syndrome.

Vitamin D deficiency and the risk of preeclampsia and eclampsia in Bangladesh.

Maternal vitamin D deficiency has been proposed as a risk factor for preeclampsia, but no significant studies have been conducted to evaluate its relationship with eclampsia. Our goal in this study was to assess the prevalence and potential risk of vitamin D deficiency for both preeclampsia and eclampsia in Bangladesh. Using a case-control design, we measured serum 25(OH)D levels in pregnant women receiving care at the Dhaka Medical College Hospital with preeclampsia (n=33), eclampsia (n=79), and normal pregnancy (controls, n=76). Odds of developing preeclampsia and eclampsia with vitamin D deficiency were calculated using logistic regression analysis. The prevalence of vitamin D insufficiency was very high with more than 3 quarters (78%) of all subjects having a serum 25(OH)D level<30 ng/ml. The mean serum 25(OH)D level was 24.86 ng/ml in controls, 23.96 ng/ml in pre-eclamptic women, and 21.56 ng/ml in eclampsia patients. Comparing to those who had a serum 25(OH)D level of ≥30 ng/ml, the odds ratio (95% CI) of developing preeclampsia and eclampsia in mothers with vitamin D insufficiency were 3.9 (95% CI=1.18-12.87) and 5.14 (95% CI=1.98-13.37), respectively (adjusting for age, BMI and duration of pregnancy). The odds of developing preeclampsia and eclampsia may increase by up to 5-fold in women with vitamin D insufficiency. Since preeclampsia and eclampsia can lead to serious complications for both mother and the offspring, vitamin D may be supplemented during pregnancy in high risk populations to decrease these adverse consequences.

Graves' disease, hypoparathyroidism, systemic lupus erythematosus, alopecia, and angioedema: autoimmune polyglandular syndrome variant or coincidence?

Data on coexisting Graves' disease (GD), hypoparathyroidism, and systemic lupus erythematosus (SLE) are limited. The thyroid and parathyroid glands may be extra sensitive to irradiation damage in an underlying autoimmune condition. A 34-year-old black woman presented with tetanic-like cramps, easy skin bruising, fatigue, weight gain, nocturia and back pain. She was previously diagnosed with GD in 2001 and underwent radioiodine therapy (RAI) in 9/01 using 6 mCi. PostRAI (November 2001) she developed hypocalcemia and hypothyroidism (2/02). In 2007, SLE was diagnosed. In October 2009, s-calcium and PTH were still low at 7.1 mg/dl and 9 pg/mL, respectively, although the patient denied symptoms on vitamin D and calcium supplementation. To identify possible autoimmune damage of the parathyroids, we evaluated the presence of activating antibodies to the CaSR and also analyzed the DNA sequence of all 6 translated exons and flanking intronic sequences of her CaSR gene for a functionally significant CaSR mutation but neither was positive. The initial autoimmune damage to her thyroid and possibly parathyroid glands followed by irradiation of them seems to have contributed to her developing both hypoparathyroidism (11/01) and hypothyroidism (2002). The patient could potentially have had parathyroid autoantibodies in 2001 that disappeared by 2009 when she was tested for them. We consider that the multiple autoimmune conditions developed over the past decade of her life with the concurrent irradiation contributing to her brittle hypoparathyroidism. Select patients with GD and perhaps parathyroid autoantibodies with a slowly developing destructive impact on the parathyroid glands may then develop overt hyoparathyroidism with rather low dose RAI ablation. This patient adds to the evolving spectrum of polyglandular syndrome variants.

11Beta-hydroxylase deficiency and other syndromes of mineralocorticoid excess as a rare cause of endocrine hypertension.

Hypertension represents a major public and global health problem, most of which likely can be improved by lifestyle changes including changing dietary habits with less consumption of processed and preserved foods, which generally contain higher amounts of salt than freshly prepared food items. Among causes for endocrine hypertension are syndromes of mineralocorticoid excess. This group of mostly monogenic and acquired disorders typically causes hypertension through activation of the mineralocorticoid receptor either directly or indirectly via hormonal mediators and from overactive amiloride-sensitive epithelial sodium channels located in the distal tubule and collecting ducts of the kidneys. Apart from primary aldosteronism, mineralocorticoid excess can be caused by congenital adrenal hyperplasia (CAH) due to mutations of the 11beta-hydroxylase and 17alpha-hydroxylase genes, by inactivating mutations of the glucocorticoid receptor gene (Chrousos syndrome), endogenous hypercortisolism (Cushing's syndrome), by mutations of the 11beta-hydroxysteroid dehydrogenase type 2 gene (apparent mineralocorticoid excess/AME) or licorice/carbenoxolone intake, mutations of the epithelial sodium channel genes (Liddle syndrome), mutations of the mineralocorticoid receptor gene (Geller syndrome), and by mutations in the WNK1, WNK4, KLHL3, CUL3 genes (pseudohypoaldosteronism type 2 or Gordon syndrome). Most of these conditions are treated by restricting dietary salt intake. However, some require special therapies including dexamethasone/hydrocortisone (CAH), spironolactone/eplerenone (AME), epithelial sodium channel inhibitors amiloride/triamterene (Liddle and Gordon syndrome), while in others spironolactone and MR antagonists may be contraindicated due to an abnormally structured MR (Geller syndrome). We here review the pathophysiology, diagnosis, and therapy of these rare conditions including the presentation of a patient with 11beta-hydroxylase deficiency.

Primary hypothyroidism associated with acute mania: case series and literature review.

In the evaluation of patients presenting with altered mental function searching for underlying medical conditions is necessary. Abnormal thyroid function has long been implicated in mood changes with the classic associations of depression occurring together with hypothyroidism and of mania along with hyperthyroidism. We here report 3 patients who presented with symptoms consistent with acute manic episode diagnosed using DSM IV-TR criteria and who were found to have primary hypothyroidism biochemically. This led to a review of the literature on this phenomenon resulting in the identification of 10 reports of mania and associated thyroid profiles consistent with primary hypothyroidism. All 3 of our patients improved clinically after use of levothyroxine and psychotropic medications, consistent with the literature reports. This illustrates that thyroid function abnormalities including primary hypothyroidism should be considered and screened for when evaluating patients with acute manic episodes.

Testosterone deficiency as a risk factor for cardiovascular disease.

Testosterone deficiency (TD) has become a frequently diagnosed condition in our current society with an obesity epidemic. Men diagnosed with TD often have co-morbidities including metabolic syndrome. Challenging aspects in diagnosing and treating patients with TD include intra-individual variation of symptoms combined with lack of its correlation with serum levels of testosterone. Apart from sexual aspects including libido and erectile function, replacement therapy with testosterone might have beneficial metabolic effects, whereas untreated TD might increase cardiometabolic risk and disease. In this article, we review the cardiovascular and metabolic risks associated with TD, as well as risks and benefits of testosterone replacement therapy. We also provide insights into potential mechanisms of the association between cardiometabolic risks with TD (treated and untreated) and propose an individual treatment algorithm.

Ectopic Cushing's syndrome caused by a well differentiated ACTH-secreting neuroendocrine carcinoma of the ileum.

Cushing's syndrome can be caused by adrenocorticotropic hormone-secreting solid tumors. We report a rare case of an ileal endocrine carcinoma that produced ACTH and induced hypercortisolism. A now 47-year-old man presented at age 41 with weight gain, tremor, perspiration, and general fatigue. Laboratory testing showed hypercortisolism and diabetes mellitus. Further examinations revealed ectopic Cushing's syndrome. The search for the primary tumor was difficult. The patient underwent subtotal thyroidectomy and surgical removal of a pituitary lesion. After resection of an ACTH-producing metastasis of the mesentery, temporary remission of Cushing's syndrome ensued. At the age 45 the primary tumor was detected in the ileum by Ga-68 DOTATOC-PET scan and explorative laparotomy. After surgical removal of this well differentiated neuroendocrine carcinoma the patient significantly improved clinically. He experienced better blood pressure and remission of his diabetes mellitus in addition to increased muscular strength. Endocrine laboratory testing at follow-up examinations confirmed remission of hypercortisolism and diabetes mellitus. A Ga-68 DOTATOC PET scan and a 1 mg dexamethasone suppression test 5 months after surgery showed normal results. Ectopic ACTH secretion within the small bowel is very rare. This case underscores the difficulty in locating the source of ectopic ACTH secretion and suggests using small bowel barium study, tubus endoscopy or video endoscopy for preoperative localization if the small bowel is suspected as tumor source.

Hypercalcemia in cancer patients: pathobiology and management.

Hypercalcemia is the most common life-threatening metabolic disorder associated with cancer, occurring in approximately 10-30% of all patients with neoplastic disease, although it occurs much less often in the pediatric setting. Hypercalcemia can emerge in hematologic malignancies, particularly multiple myeloma, as well as assorted solid tumors, primarily lung and breast cancers, and can even dominate the clinical picture in select patients. Early diagnosis and treatment with fluids and drugs that lower calcium levels in the blood can improve symptoms in a few days, ameliorate the quality of life of these patients, and avoid delays in the implementation of further anticancer treatments. Occasionally, the symptoms of hypercalcemia can appear gradually, and may be non-specific, resembling symptoms of many cancers and other comorbidities, especially in the elderly, thus resulting in an underestimated incidence of hypercalcemia in cancer patients. Of note, there is an increasing number of antineoplastic compounds that can interfere with calcium metabolism. Taking into consideration both the severity of hypercalcemia and the tumor status, health care providers should determine and apply appropriate treatment measures. We provide a comprehensive subjective synthesis of peer-reviewed evidence on the pathophysiology and treatment of hypercalcemia in cancer patients.

Vertebroplasty, first 1000 levels of a single center: evaluation of the outcomes and complications.

BACKGROUND AND PURPOSE: Percutaneous polymethylmethacrylate (PMMA) vertebroplasty has become a common procedure for treatment of pain and disability associated with vertebral compression fractures. We reviewed the experience with our first 1000 consecutively treated vertebral compression fractures in an attempt to demonstrate both the short- and long-term safety and efficacy of percutaneous vertebroplasty. MATERIALS AND METHODS: The first 1000 compression fractures treated by vertebroplasty at our institution were identified from a comprehensive prospectively acquired vertebroplasty data base. All patients treated with vertebroplasty were included, regardless of the underlying pathologic cause. Chart reviews of the procedure notes, imaging studies, clinical visits, and follow-up telephone interviews were performed for each patient. Evaluation at each follow-up time point included pain response (subjective and visual analog pain score), change in mobility, change in pain medication usage, and modified Roland-Morris Disability Questionnaire. Statistical analysis was performed on the pain response and change in the Roland-Morris score at each follow-up time point. Significant procedure-related complications that occurred from the time of the procedure were also specifically extracted from the patients' charts. RESULTS: There was a dramatic improvement in all the evaluated parameters following percutaneous vertebroplasty. The improvement in pain, mobility, medication usage, and Roland-Morris score was noticed immediately after the procedure and persisted through the 2-year follow-up. There was a low rate of complications from the procedure, the most common being rib fractures. CONCLUSION: According to our results, practitioners can quote a high success rate and low complication rate for vertebroplasty when making treatment recommendations for painful spinal compression fractures.

Outcomes of patients receiving long-term corticosteroid therapy who undergo percutaneous vertebroplasty.

BACKGROUND AND PURPOSE: The purpose of this study was to determine the efficacy and rate of complications in patients undergoing percutaneous vertebroplasty (PVP) for vertebral compression fractures as a result of secondary osteoporosis caused by long-term corticosteroid use compared with patients with primary osteoporosis treated with PVP. MATERIALS AND METHODS: A retrospective review of all patients undergoing PVP was conducted to identify patients who also received long-term corticosteroid therapy. Outcomes including pain, periprocedural complications, and frequency of new fractures in patients receiving corticosteroids were compared with control patients undergoing PVP for primary osteoporosis. RESULTS: Sixty-eight patients receiving long-term corticosteroid therapy underwent 79 PVP procedures. Patients treated with corticosteroids undergoing PVP were significantly younger and more likely to be male compared with control subjects. Patients receiving long-term corticosteroid treatment experienced significant pain relief immediately postprocedure and at 1 week, 1 month, 6 months, 1 year and 2 years postprocedure (P < .0001 at all time points). Patients receiving corticosteroids experienced similar decreases in pain from baseline compared with control subjects at all follow-up time points (P > .05). The complication rate for patients receiving corticosteroids was 4.4% compared with 3.4% for control subjects (P = .60). Patients on long-term corticosteroid treatment did not have an increased risk of new fractures after PVP compared with control subjects (P = .68). CONCLUSIONS: Percutaneous vertebroplasty performed for vertebral compression fractures as a result of long-term corticosteroid therapy is as safe and effective in relieving pain as PVP performed in patients with vertebral compression fractures as a result of primary osteoporosis.

Central diabetes insipidus in a patient with malaria tropica.

Up to 21% of severe cases of malaria tropica are associated with polyuria and are life-threatening. We describe a 39-yr-old man with malaria tropica who developed disseminated intravascular coagulation, polyuria, and a pituitary lesion. Empiric treatment with vasopressin improved the polyuria. This is the first case of malaria tropica in which central diabetes insipidus has been documented.

Citalopram therapy as a risk factor for symptomatic hyponatremia caused by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH): a case report.

We report the case of an 81-year old woman with stupor, confusion, somnolence, vomiting, and reduced food intake for 5 days. Laboratory investigations revealed low serum concentrations of sodium and potassium with a serum osmolality of 225 mOsm/kg H (2)O in the face of an inappropriately concentrated urine with an osmolality in the normal range, suggesting the syndrome of inappropriate antidiuretic hormone secretion (SIADH) in the absence of renal insufficiency, adrenal insufficiency, and hypothyroidism. Careful drug evaluation revealed amitriptyline and citalopram as possible inciters of antidiuretic hormone secretion. Subsequently, these drugs were withdrawn. Under continuous sodium substitution and fluid restriction serum sodium normalized and the patient's symptoms resolved. She was fully alert by day 15. We conclude that hyponatremia secondary to SIADH was the cause of the patient's neurologic symptoms. Clinicians should be aware of this possible side effect of central acting agents such as amitriptyline and citalopram, drugs that are often used to treat elderly patients suffering from depression or chronic pain.

Evaluation of thin films of agarose on glass for hybridization of DNA to identify plant pathogens with microarray technology.

Agarose-coated glass slides, after activation, were spotted with amine-modified oligonucleotide probes using a manual eight-pin arraying device. Two probes, designed to identify two common greenhouse fungal plant pathogens, Didymella bryoniae and Botrytis cinerea, were hybridized with polymerase chain reaction (PCR)-amplified fluorescently labeled DNA extracted from pure culture and from diseased plant tissue. The probes easily distinguished these pathogens from each other without cross reaction. Thickness of the agarose layer and length of the sample DNA were important factors affecting hybridization efficiency of immobilized probe to PCR product. These factors did not affect hybridization with short complementary oligonucleotide. Probes fixed on agarose-coated slides could differentiate samples as readily as probes on nylon but with potentially higher spot density and gave much better signal than probes on silylated slides. The use of plain glass slides, agarose, and a manual arrayer makes this technique useful for developing specialized and inexpensive DNA microarrays on a solid rigid substrate.