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1
Pu, Shuqi, Xiaojie Wu, Xiaoying Yang, Yunzhan Zhang, Yunkai Dai, Yueling Zhang, Xiaoting Wu, et al. "The Therapeutic Role of Xenobiotic Nuclear Receptors Against Metabolic Syndrome." Current Drug Metabolism 20, no. 1 (March 11, 2019): 15–22. http://dx.doi.org/10.2174/1389200219666180611083155.
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Background: Diabetes, with an increased prevalence and various progressive complications, has become a significant global health challenge. The concrete mechanisms responsible for the development of diabetes still remain incompletely unknown, although substantial researches have been conducted to search for the effective therapeutic targets. This review aims to reveal the novel roles of Xenobiotic Nuclear Receptors (XNRs), including the Peroxisome Proliferator-Activated Receptor (PPAR), the Farnesoid X Receptor (FXR), the Liver X Receptor (LXR), the Pregnane X Receptor (PXR) and the Constitutive Androstane Receptor (CAR), in the development of diabetes and provide potential strategies for research and treatment of metabolic diseases. Methods: We retrieved a large number of original data about these five XNRs and organized to focus on their recently discovered functions in diabetes and its complications. Results: Increasing evidences have suggested that PPAR, FXR, LXR ,PXR and CAR are involved in the development of diabetes and its complications through different mechanisms, including the regulation of glucose and lipid metabolism, insulin and inflammation response and related others. Conclusion: PPAR, FXR, LXR, PXR, and CAR, as the receptors for numerous natural or synthetic compounds, may be the most effective therapeutic targets in the treatment of metabolic diseases.
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Wang, Yun, Yue Zheng, Patsy M. Nishina, and Jürgen K. Naggert. "A new mouse model of metabolic syndrome and associated complications." Journal of Endocrinology 202, no. 1 (April 24, 2009): 17–28. http://dx.doi.org/10.1677/joe-09-0079.
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Metabolic syndrome (MS) encompasses a clustering of risk factors for cardiovascular disease, including obesity, insulin resistance, and dyslipidemia. We characterized a new mouse model carrying a dominant mutation, C57BL/6J-Nmf15/+ (B6-Nmf15/+), which develops additional complications of MS such as adipose tissue inflammation and cardiomyopathy. A backcross was used to genetically map the Nmf15 locus. Mice were examined in the comprehensive laboratory animal monitoring system, and dual energy X-ray absorptiometry and blood chemistry analyses were performed. Hypothalamic LEPR, SOCS1, and STAT3 phosphorylation were examined. Cardiac function was assessed by echo- and electrocardiography. Adipose tissue inflammation was characterized by in situ hybridization and measurement of Jun kinase activity. The Nmf15 locus mapped to distal mouse chromosome 5 with an LOD (logarithm of odds) score of 13.8. Nmf15 mice developed obesity by 12 weeks of age. Plasma leptin levels were significantly elevated in pre-obese Nmf15 mice at 8 weeks of age and an attenuated STAT3 phosphorylation in the hypothalamus suggests a primary leptin resistance. Adipose tissue from Nmf15 mice showed a remarkable degree of inflammation and macrophage infiltration as indicated by expression of the F4/80 marker and increased phosphorylation of JUN N-terminal kinase 1/2. Lipidosis was observed in tubular epithelial cells and glomeruli of the kidney. Nmf15 mice demonstrate both histological and pathophysiological evidence of cardiomyopathy. The Nmf15 mouse model provides a new entry point into pathways mediating leptin resistance and obesity. It is one of few models that combine many aspects of MS and can be useful for testing new therapeutic approaches for combating obesity complications, particularly cardiomyopathy.
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Correia, Marcelo L. G., and Kamal Rahmouni. "Role of leptin in the cardiovascular and endocrine complications of metabolic syndrome." Diabetes, Obesity and Metabolism 8, no. 6 (November 2006): 603–10. http://dx.doi.org/10.1111/j.1463-1326.2005.00562.x.
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Gohil, Baiju C., Leonard A. Rosenblum, Jeremy D. Coplan, and John G. Kral. "Hypothalamic-Pituitary-Adrenal Axis Function and the Metabolic Syndrome X of Obesity." CNS Spectrums 6, no. 7 (July 2001): 581–89. http://dx.doi.org/10.1017/s1092852900002121.
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AbstractObesity has negative health consequences related to fat distribution, particularly the central or visceral accumulation of fat. The major complications associated with visceral obesity, termed the “Metabolic Syndrome of Obesity,” or “Syndrome X,” are type II diabetes, hypertension, and dyslipidemia. As with certain mood disorders, the syndrome may be a consequence of neuroendocrine perturbations typically associated with chronic stress. Our work with bonnet macaque monkeys provides an animal model for the relationship between early stress, behavioral and hypothalamic-pituitary-adrenal (HPA) axis dysregulation, and Syndrome X. During their infant's first half-year, mothers face a variable foraging demand (VFD), in which ample food varies unpredictably in the difficulty of its acquisition, and the offspring show persistent abnormalities in systems known to modulate stress and affective regulation. Early work on the bonnet macaque noted the emergence of a sample of spontaneously obese subjects as they matured. Using the VFD model, the current study showed that there was a clear relationship between early cerebrospinal fluid corticotropin-releasing factor levels and subsequently measured body mass index, supporting the hypotheses regarding the interactive roles of early experience and HPA axis dysregulation in the ontogeny of both metabolic and mood disorders.
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Blaslov, Kristina, Tomislav Bulum, Jadranka Knežević-Ćuća, and Lea Duvnjak. "Relationship between autoantibodies combination, metabolic syndrome components and diabetic complications in autoimmune diabetes in adults." Endocrine 48, no. 2 (June 27, 2014): 551–56. http://dx.doi.org/10.1007/s12020-014-0331-x.
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Sahin, Cahit, Bilal Eryildirim, A. Cihangir Cetinel, Gokhan Faydaci, Fehmi Narter, Cemal Goktas, and Kemal Sarica. "Does metabolic syndrome increase the risk of infective complications after prostate biopsy? A critical evaluation." International Urology and Nephrology 47, no. 3 (January 15, 2015): 423–29. http://dx.doi.org/10.1007/s11255-014-0904-x.
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Kowalski, J., J. Błaszczyk, M. Barylski, R. Irzmański, E. Brocka, A. Lewiński, and L. Pawlicki. "PO21-636 ESTIMATION OF CARDIOVASCULAR COMPLICATIONS AND DEATH RISK IN SUBJECTS WITH METABOLIC SYNDROME (MS)." Atherosclerosis Supplements 8, no. 1 (June 2007): 172. http://dx.doi.org/10.1016/s1567-5688(07)71646-x.
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Miele, Luca, Giovanni Gasbarrini, Valentina Giorgio, Antonio Gasbarrini, and Antonio Grieco. "Nonalcoholic fatty liver disease as trigger of cardiovascular and metabolic complication in metabolic syndrome." Internal and Emergency Medicine 11, no. 1 (November 24, 2015): 3–10. http://dx.doi.org/10.1007/s11739-015-1346-x.
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Okabe, Emiko, Minoru Takemoto, Shunichiro Onishi, Takahiro Ishikawa, Ryouichi Ishibashi, Peng He, Kazuki Kobayashi, Masaki Fujimoto, Harukiyo Kawamura, and Koutaro Yokote. "Incidence and Characteristics of Metabolic Disorders and Vascular Complications in Individuals with Werner Syndrome in Japan." Journal of the American Geriatrics Society 60, no. 5 (May 2012): 997–98. http://dx.doi.org/10.1111/j.1532-5415.2012.03944.x.
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Martocchia, Antonio, Silvia Cola, Patrizia Frugoni, Ilaria Indiano, Rosaria D’Urso, and Paolo Falaschi. "The burden of comorbidity and the C-reactive protein levels in nonthyroidal illness syndrome with metabolic syndrome and atherosclerosis-related cardiovascular complications." Annals of the New York Academy of Sciences 1193, no. 1 (April 2010): 164–66. http://dx.doi.org/10.1111/j.1749-6632.2009.05291.x.
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Edriss, Hawa, and Marie Pfarr. "Acute respiratory distress syndrome, metabolic acidosis, and respiratory acidosis associated with citalopram overdose." Southwest Respiratory and Critical Care Chronicles 2, no. 5 (November 19, 2013): 24. http://dx.doi.org/10.12746/swrccc.v2i5.102.
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We report a 53-year-old man who ingested 2400 mg of citalopram and presented to the emergency department three hours post-ingestion with altered mental status, somnolence, and a blood pressure of 67/45 mmHg. He failed to respond to three boluses of normal saline (1000 ml each) and required vasopressors. The patient developed serotonin syndrome with hyper-reflexia, rigidity, and ankle myoclonus. He had a tonic-clonic seizure in the ER requiring intravenous lorazepam and phenytoin. An ECG showed QT prolongation. Chest x-ray on presentation was normal. Within 32 hours the patient developed acute respiratory distress, hypoxemia, a wide A-a gradient, PaO2/FiO2< 200, and chest x-ray changes compatible with acute respiratory distress syndrome (ARDS). He had normal central venous pressures, normal cardiac biomarkers, normal systolic and diastolic functions on echocardiography, and no acute ST/T wave changes. His ABG showed a metabolic acidosis and a respiratory acidosis. The patient required intubation and ventilation. Citalopram has been associated with seizures and ECG abnormalities after overdoses. The respiratory complications and metabolic acidosis have been reported only a few times in the literature. We are reporting the second case of ARDS and the fifth case of metabolic acidosis due to citalopram overdose and suggest that the metabolic acidemia is explained by propionic acid. The respiratory acidosis seen in this patient has not been reported previously.
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Muntz, H. G., and E. Brown. "Lactic acidosis and hypoglycemia: a metabolic complication of advanced gynecologic malignancy." International Journal of Gynecologic Cancer 2, no. 3 (1992): 163–67. http://dx.doi.org/10.1046/j.1525-1438.1992.02030163.x.
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Refractory lactic acidosis and hypoglycemia characterize a paraneoplastic syndrome observed in advanced gynecologic cancer, as illustrated by a patient with a large malignant mixed Mullerian tumor. Massive infusions of sodium bicarbonate and glucose failed to reverse her metabolic abnormalities, and the patient suffered a rapidly fatal course. The biochemical basis for this metabolic complication is reviewed, including how medical intervention can lead to iatrogenic exacerbation of the metabolic imbalance.
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Costa, L. A., L. H. Canani, H. R. K. Lisbôa, G. S. Tres, and J. L. Gross. "Aggregation of features of the metabolic syndrome is associated with increased prevalence of chronic complications in Type 2 diabetes." Diabetic Medicine 21, no. 3 (February 17, 2004): 252–55. http://dx.doi.org/10.1111/j.1464-5491.2004.01124.x.
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Debin, Régine, Benjamin Lauzier, Pierre Sicard, Stéphanie Delemasure, Sébastien Amoureux, Laurence Duvillard, Catherine Vergely, Yves Cottin, and Luc Rochette. "Are Zucker obese rats a useful model for cardiovascular complications in metabolic syndrome? Physical, biochemical and oxidative stress considerations." Fundamental & Clinical Pharmacology 23, no. 1 (February 2009): 59–67. http://dx.doi.org/10.1111/j.1472-8206.2008.00659.x.
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Li, Chao, Yunlun Li, and Zhibo Gai. "Bile Acids and Farnesoid X Receptor: Novel Target for the Treatment of Diabetic Cardiomyopathy." Current Protein & Peptide Science 20, no. 10 (September 20, 2019): 976–83. http://dx.doi.org/10.2174/1389203720666190726152847.
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Diabetes mellitus (DM) has become an increasingly common disease with high disability and mortality rates. Diabetes complications are the main cause of diabetes death and about 50% of diabetic patients died from heart disease in developed countries reported by World Health Organization. Diabetic cardiomyopathy (DCM) has been considered as a high incidence and serious complication of DM and plays a key role in the incidence and development of diabetes related heart failure. Metabolism dysregulation is regarded as an important and earlier factor occurred in the pathogenesis of DCM. Insulin resistance, oxidative stress, inflammation and mitochondrial dysfunction also contribute to the development of DCM. Farnesoid X Receptor (FXR) is a member of nuclear receptor superfamily, and plays a critical role in regulating lipid and glucose metabolism, oxidative stress and inflammation. FXR is activated by primary bile acids (BAs) such as chenodeoxycholic acid, cholic acid and synthetic agonists such as obeticholic acid. BAs are the main active ingredients of many natural products and traditional medicines, especially bile or gallstones in animals, such as calculus bovis. Due to the regulatory effect of FXR on glucose and lipid metabolism, oxidative stress and inflammation, the treatment of BAs and FXR agonists for metabolic syndrome and DCM have gained more attention. This review will focus on the pathogenesis of diabetic cardiomyopathy and the regulatory effect of BAs and FXR on DCM.
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Bonora, E., G. Targher, G. Formentini, F. Calcaterra, S. Lombardi, F. Marini, L. Zenari, et al. "The Metabolic Syndrome is an independent predictor of cardiovascular disease in Type 2 diabetic subjects. Prospective data from the Verona Diabetes Complications Study." Diabetic Medicine 21, no. 1 (January 2004): 52–58. http://dx.doi.org/10.1046/j.1464-5491.2003.01068.x.
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Gaballa, Salem, Areeka Memon, and Marigny Roberts. "Atypical Adrenocortical Incidentaloma Causing Autonomous Cortisol Secretion and Cardiovascular Complications." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A118. http://dx.doi.org/10.1210/jendso/bvab048.237.
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Abstract Introduction: Autonomous cortisol secretion (ACS) is found in approximately 10% of patients with an adrenocortical incidentaloma (AI). The majority of these cases are due to non-ACTH-dependent ACS. 2% of patients with AI have adrenocortical cancer. ACS is associated with cardiovascular morbidity, includes arterial stiffness, hypertension, coronary heart disease, and fatal or nonfatal myocardial infarction. Case presentation: A 62-year-old Caucasian male with a history of hypertension (HTN), hyperlipidemia (HLD) and poorly controlled type-2 diabetes mellitus (T2DM) and a recent myocardial infarction (MI) status post (s/p) coronary artery bypass graft (CABG) who presented to the endocrine clinic for evaluation of left adrenal mass. Family history was significant for adrenal carcinoma of his brother at the age of 60. The patient denied any facial flushing, palpitations, tremors, heat or cold intolerance, abnormal sweating, diarrhea, constipation, abdominal pain, recent weight change. Physical examination was unremarkable except midline sternal scar s/p CABG. Vital signs were remarkable for a blood pressure of 142/90. Labs were unremarkable. CT adrenal revealed a left adrenal mass 4.9 x 3.5 x 2.3 cm with HU -3 to 28 heterogeneous. HbA 1C was 8.2 %. Adrenal incidentaloma workup revealed a normal 24-hour urine cortisol level of 29 mcg, abnormal mid-night salivary cortisol of 0.13 mcg/dL and 0.31 mcg/dL, elevated cortisol after 1 mg dexamethasone suppression test (DST) of 343 mcg/dL, elevated cortisol after 8 mg DST of 90 mcg/dL, normal metanephrines of 10 pg/mL and normal normetanephrine of 49 pg/mL, normal aldosterone of 6.1 ng/dL, normal renin activity of 0.36 ng/ml/hr (Aldo/ PRA ratio 16). ACTH was 4.5 pg/ml. The endocrine surgeon was consulted for left adrenalectomy. The pathology showed atypical adrenal cortical neoplasm which does not clearly fulfill the criteria for adrenal cortical carcinoma confirmed by two pathologists. Upon six months follow-up, a 24-hour urine cortisol level was normal, 1mg overnight DST was normal, and no evidence of left adrenal on adrenal CT. Discussion: Adrenal incidentaloma (AI) is a common endocrine diagnosis affecting ~2% of the general population. Up to 10% of patients with AI have autonomous secretion of adrenal hormones. Pheochromocytoma and autonomous cortisol secretion should be excluded in every case and aldosteronism in patients with underlying hypertension and/or hypokalemia. ACS in patients AI has been associated with hypertension, insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome, coronary artery disease, and increased mortality. Adrenalectomy is recommended for patients with a functional unilateral adenoma, with clinically significant hormone excess. Metabolic improvement after adrenalectomy, including weight loss, blood pressure lowering, glucose tolerance, lower lipids have been reported.
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Brufani, Claudia, Danilo Fintini, Ugo Giordano, Alberto Enrico Tozzi, Fabrizio Barbetti, and Marco Cappa. "Metabolic Syndrome in Italian Obese Children and Adolescents: Stronger Association with Central Fat Depot than with Insulin Sensitivity and Birth Weight." International Journal of Hypertension 2011 (2011): 1–6. http://dx.doi.org/10.4061/2011/257168.
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Aim. To evaluate whether body fat distribution, birth weight, and family history for diabetes (FHD) were associated with metabolic syndrome (MetS) in children and adolescents.Methods. A total of 439 Italian obese children and adolescents (5–18 years) were enrolled. Subjects were divided into 2 groups: prepubertal and pubertal. MetS was diagnosed according to the adapted National Cholesterol Education Program criteria. Birth weight percentile, central obesity index (measured by dual-energy X-ray absorptiometry), insulin sensitivity (ISI), and disposition index were evaluated. Multivariate logistic regression models were used to determine variables associated with MetS.Results. The prevalence of MetS was 17%, with higher percentage in adolescents than in children (21 versus 12%). In the overall population, central obesity index was a stronger predictor of MetS than insulin sensitivity and low birth weight. When the two groups were considered, central fat depot remained the strongest predictor of MetS, with ISI similarly influencing the probability of MetS in the two groups and birth weight being negatively associated to MetS only in pubertal individuals. Neither FHD nor degree of fatness was a significant predictor of MetS.Conclusion. Simple clinical parameters like increased abdominal adiposity and low birth weight could be useful tools to identify European obese adolescents at risk for metabolic complications.
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Fasen, Madeline, Kent R. Wehmeier, and Poonam Kalidas Kapadia. "Dual Adenomas: Detection of Cushing’s Syndrome of Adrenal Origin During Evaluation of Pituitary Macroadenoma." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A127—A128. http://dx.doi.org/10.1210/jendso/bvab048.257.
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Abstract Cushing’s syndrome is a rare and often severe disease associated with increased mortality and major metabolic complications with cardiovascular disease as the main cause of death. Adrenal masses are most often found by radiographic studies or autopsy as incidentalomas. The prognosis of Cushing’s syndrome is mainly affected by the difficulties in timely diagnosis and treatment of the disease, which remain a challenge due to its nonspecific presentation and multitude of etiologies. Herein, we present an atypical case of adrenal Cushing’s syndrome unveiled by the workup of a nonfunctioning pituitary macroadenoma. A 62 year-old woman presented with new intermittent headaches and worsening vision changes for the past year. She was found to have a large sellar mass measuring 2.7 x 2.4 x 3.0 cm invading the right cavernous sinus with displacement of the optic chiasm on brain magnetic resonance imaging (MRI). In the interim to neurosurgical evaluation, lab work performed to assess pituitary function showed an elevated late night salivary cortisol at 0.200 UG/DL (0.010–0.090 UG/DL range). Low early morning ACTH and elevated late night salivary cortisol, dexamethasone suppression test and 24 hour urine cortisol were observed and confirmed with repeat studies. These findings warranted a computed tomography (CT) adrenal mass protocol which revealed a left adrenal lesion consistent with a lipid rich adenoma measuring 4.9 x 3.5 x 4.1 cm in size. Subsequent urine catecholamines and metanephrines were within normal limits. The patient was admitted for transphenoidal pituitary resection with perioperative stress dose corticosteroids, but was only able to achieve partial resection due to large tumor size. Post-operatively the patient did well on a quick corticosteroid taper down to hydrocortisone 15 mg in AM and 5 in afternoon with hope to wean in the near future. Post-operative workup showed ACTH 4.6 pg/mL (7.2 – 63.3 pg/mL) and 8 am cortisol 24.7 MCG/DL (6.2–19.4 MCG/DL) which suggests autonomous adrenal secretion of cortisol. Once the patient has recovered from her partial pituitary resection she will be referred to general surgery for adrenalectomy. This case provided a review of a classic pituitary macroadenoma workup with an interesting twist to Cushing’s etiology as the cause was not from the pituitary as originally thought.
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Haugen, Fred, and Christian A. Drevon. "The interplay between nutrients and the adipose tissue." Proceedings of the Nutrition Society 66, no. 2 (April 30, 2007): 171–82. http://dx.doi.org/10.1017/s0029665107005423.
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The importance of adipose tissue in health as well as disease has been demonstrated in several studies recently, and it has become appropriate to use the term ‘adipose organ’ when referring to adipose tissue as a whole. The obesity epidemic, with a marked increase in the incidence of the metabolic syndrome leading to diabetes type 2 as well as cardiovascular complications, has stimulated considerable interest in adipose tissue biology. Moreover, several studies in different species have shown that limited energy intake is associated with less inflammation, improved biomarkers of health and a marked increase in longevity. In addition, there is convincing evidence that an optimal amount of adipose tissue is essential for many body functions such as immune response, reproduction and bone quality. Some nutrients and their metabolites are important as energy sources as well as ligands for many transcription factors expressed in adipose tissue, including all energy-providing nutrients both directly and indirectly as well as cholesterol, vitamin E and vitamin D. In particular, fatty acids can be effectively taken up by adipocytes and they can interact with several transcription factors crucial for growth, development and metabolic response, e.g. PPARα, −δ and −γ, sterol regulatory element-binding proteins1 and 2 and liver X receptors α and β). Moreover, glucose is also readily taken up and stored as fatty acids via lipogenesis in adipocytes. It is known that some metabolic signals released as proteins from adipose tissue (adipokines) are important for normal as well as pathological responses to the amount of energy stored in the adipose organ. The future challenge will be to understand the function of adipose tissue in energy homeostasis and the interplay with nutrients in order to be able to give optimal advice for the prevention and treatment of obesity.
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Kalman, R., E. Ziv, E. Shafrir, H. Bar-On, and R. Perez. "Psammomys obesus and the albino rat-two different models of nutritional insulin resistance, representing two different types of human populations." Laboratory Animals 35, no. 4 (October 1, 2001): 346–52. http://dx.doi.org/10.1258/0023677011911949.
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Animal models for insulin resistance and type 2 diabetes are required for the study of the mechanism of these phenomena and for a better understanding of diabetes complications in human populations. Type 2 diabetes is a syndrome that affects 5-10% of the adult population. Hyperinsulinaemia, hypertriglyceridaemia, decreased high-density lipoprotein (HDL) cholesterol levels, obesity and hypertension, all form a cluster of risk factors that increase the risk of coronary artery disease, and are known as insulin resistance syndrome or syndrome X. The gerbil, Psammomys obesus is characterized by primary insulin resistance and is a well-defined model for dietary induced type 2 diabetes. Weanling Psammomys and Albino rats were held individually for several weeks on high energy (HE) and low energy (LE) diets in order to determine the development of metabolic changes leading to diabetes. Feeding Psammomys on HE diet resulted in hyperglycaemia (303 ± 40 mg/dl), hyperinsulinaemia (194 ± 31 µU/ml) and a moderate elevation in body weight, obesity and plasma triglycerides. Albino rats on HE diet demonstrated an elevation in plasma insulin (30 ± 4 µU/ml), hypertriglyceridaemia (170 µ 11 mg/dl), an elevation in body weight and obesity, but maintained normoglycaemia (98 µ 6 mg/dl). Psammomys represent a model that is similar to human populations, with primary insulin resistance expressed in young age, which leads to a high percentage of adult type 2 diabetes. Examples for such populations are the Pima Indians, Australian Aborigines and many other Third World populations. The results indicate that the metabolism of Psammomys is well adapted towards life in a low energy environment, where Psammomys takes advantage of its capacity for a constant accumulation of adipose tissue that will serve for maintenance and breeding in periods of scarcity. This metabolism known as 'thrifty metabolism', is compromised at a high nutrient intake.
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Dumaine, Raphaelle, C. Michael Gibson, Sabina A. Murphy, Matthew Southard, Hung Q. Ly, Carolyn H. McCabe, Robert P. Giugliano, Christopher P. Cannon, Elliott M. Antman, and Eugene Braunwald. "Association of a History of Systemic Hypertension With Mortality, Thrombotic, and Bleeding Complications Following Non-ST-Segment Elevation Acute Coronary Syndrome." Journal of Clinical Hypertension 8, no. 5 (May 2006): 315–22. http://dx.doi.org/10.1111/j.1524-6175.2006.05384.x.
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Bouchard, Luigi, Marie-Claude Vohl, Yves Deshaies, Caroline Rhéaume, Marleen Daris, and André Tchernof. "Visceral adipose tissue zinc finger protein 36 mRNA levels are correlated with insulin, insulin resistance index, and adiponectinemia in women." European Journal of Endocrinology 157, no. 4 (October 2007): 451–57. http://dx.doi.org/10.1530/eje-07-0073.
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Introduction: Adipose tissue is now recognized as an endocrine organ and secretes numerous molecules and proteins potentially involved in the physiopathology of the metabolic syndrome. Recently, we have determined the transcriptome of omental adipose tissue, leading to the identification of a new candidate gene for obesity-related metabolic complications, zinc finger protein 36 (ZFP36), which is known to down-regulate tumor necrosis factor-α TNF-α) expression. Objective: The objective of this study was to further examine the relationship between ZFP36 gene expression levels, obesity-related phenotypes, and adipokines. Methods: Abdominal subcutaneous and omental adipose tissue samples were obtained from 46 women undergoing elective gynecological surgery. Adipose tissue ZFP36 mRNA abundance was assessed by quantitative real-time PCR. Body fat accumulation and distribution were measured by dual X-ray absorptiometry and computed tomography. Fasting blood levels of glucose, insulin, and lipids, and circulating TNF-α, interleukin-6 (IL-6), resistin, and adiponectin were also measured. Results: No correlation was observed between s.c. ZFP36 mRNA levels and any of the phenotypes tested. However, although omental ZFP36 mRNA levels were not correlated with measures of body fatness and lipid profile, they were negatively correlated with fasting insulin levels (R = −0.31; P = 0.05), the insulin resistance index (HOMA-IR; R = −0.31; P = 0.05), and 2-h post-glucose insulinemia (R = −0.32; P = 0.05). Omental ZFP36 mRNA abundance was also positively correlated with adiponectinemia (R = 0.35; P = 0.03) but not with circulating TNF-α, IL-6, and resistin concentrations. Conclusion: These results suggest that ZFP36 gene expression in omental adipose tissue, but not in abdominal s.c. fat, may offer partial protection against the development of insulin resistance and diabetes.
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Dye, Alyssa M., Sandra R. Arnold, Terri H. Finkel, and Ahlee Kim. "A Case of Severe MIS-C in Pediatric Diabetes: Complications of COVID-19." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A692—A693. http://dx.doi.org/10.1210/jendso/bvab048.1410.
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Abstract Background: Multisystem inflammatory syndrome in children (MIS-C) is a serious inflammatory response to a prior coronavirus disease of 2019 (COVID-19), characterized by fever, inflammation, and multiorgan dysfunction. Current literature does not indicate a relationship between pediatric diabetes and risk of developing MIS-C. Here, we report a case of pediatric type 2 diabetes (T2D) with diabetic ketoacidosis (DKA) and severe multi-organ dysfunction with SARS-CoV-2 serology positivity. Clinical Case: A 13-year-old African American female with obesity (Body Mass Index >99th %) and poorly controlled T2D (HbA1c 12.8%) presented to the emergency department for one week of sore throat, headache, and abdominal pain. SARS-CoV-2 positivity was confirmed by PCR. The next day, she was found unconscious at home. She was diagnosed with DKA and was directly admitted to the pediatric intensive care unit. IV insulin and aggressive fluid resuscitation were initiated and her DKA resolved over the next 72 hrs. However, she exhibited continued altered mental status with slurred speech and significant respiratory distress requiring respiratory support. Due to the severe presentation and multi-organ involvement, a multi-disciplinary care team was formed. Further workup confirmed acute respiratory distress syndrome with pneumonia; severe acute kidney injury (AKI, creatinine of 4.56 mg/dL); presumed myocarditis (ST elevation on EKG, troponin 4.47 ng/mL, BNP 129.8 pg/mL); punctuate intraparenchymal hemorrhage in the splenium of the corpus callosum; transaminitis (AST 188 u/L, ALT 100 u/L); pancreatitis (amylase 651 u/L, lipase >9500 u/L); thrombocytopenia with consumptive coagulopathy (platelet 81 X 103/µL, d-dimer 5.91 mcg FEU/mL), increased inflammatory markers (ESR 53 mm/hr, ferritin 127 ng/mL), and positive SARS-CoV-2 serology. A presumed diagnosis of MIS-C was made per the Centers for Disease Control and Prevention definition and she was started on dexamethasone and intravenous immunoglobulin (IVIG). While consideration was given to the possibility of acute COVID-19 infection in combination with DKA, she was not a candidate for remdesivir due to AKI. On day 12, she developed new dysarthria, dyspraxia and behavioral changes. Encephalopathy workup was negative (CSF Encephalopathy autoimmune panel negative, NMDA receptor negative) and she was restarted on dexamethasone and IVIG. She was discharged on day 28. Conclusion: There is a paucity of literature of MIS-C associated with COVID-19 in the pediatric diabetes. Our case highlights several novel aspects of MIS-C with concurrent poorly controlled diabetes and DKA, including severe central nervous system manifestations and prolonged hospitalization. Further studies are warranted to elucidate an association between pediatric diabetes and MIS-C and to develop guidelines for management of MIS-C in poorly controlled pediatric diabetes.
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Miller, Weston P., Melisa Kay Stricherz, Cathryn Jennissen, Nicole Sando, Jennifer Danielson, Troy Lund, and Paul J. Orchard. "High-Exposure, Targeted Daily Busulfan and Fludarabine-Based Conditioning for Children Undergoing Hematopoietic Stem Cell Transplantation for Inherited Metabolic Disorders: Outcomes at a Single Center." Blood 128, no. 22 (December 2, 2016): 2191. http://dx.doi.org/10.1182/blood.v128.22.2191.2191.
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Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) has emerged as standard therapy for children suffering from various life-threatening inherited metabolic disorders (IMD). Historically, successful outcomes have been limited by high rates of both graft failure and regimen-related toxicity. Real-time busulfan pharmacokinetic monitoring, combined with once daily dosing, has allowed for more precise delivery of targeted exposures during transplant conditioning. Recently, the Utrecht group reported highly favorable outcomes following a high-dose busulfan and fludarabine-based preparative regimen in patients with a variety of diagnoses, particularly in comparison to historical regimens that employ two or more alkylating agents. We report our experience using the same regimen specifically in patients with IMD. Since July 2014, 24 children undergoing first HSCT for IMD were conditioned with once daily IV busulfan (4 days; total regimen exposure of 90 mg x h/L) and once daily IV fludarabine (40 mg/m2/day x 4 days). Busulfan pharmacokinetic monitoring was performed on each of the first 3 doses (days); subsequent doses were altered to achieve the desired total regimen exposure. Serotherapy use was donor-dependent: HLA-matched related donor (MRD, n = 5), none; unrelated UCB (n = 16), thymoglobulin (2.5 mg/kg/day, days - 8 to -5); HLA-matched unrelated donor (MUD, n = 1), thymoglobulin (2.5 mg/kg/day, days - 5 -to -2); and, related HLA haploidentical marrow (n = 2), alemtuzumab (0.5 mg/kg divided days -11 and -10), +/- rituximab (375 mg/m2, day -12). All patients received CSA for GvHD prophylaxis. Additional GvH prophylaxis depended upon the allograft source: UCB, prednisolone; MRD/MUD, MMF; related haploidentical, MMF and post-transplant cyclophosphamide. Growth factor support was administered to recipients of UCB or haploidentical grafts. IMD diagnoses were as follows: Hurler syndrome (n = 10); cerebral adrenoleukodystrophy (n = 9); metachromatic leukodystrophy (n = 1); osteopetrosis (n = 1); fucosidosis (n = 1); alpha-mannosidosis (n = 1); and, beta-mannosidosis (n = 1). At a median follow-up of 229 days (range, 15 - 743), 22 of 24 patients survive, with a Kaplan Meier estimate of survival at one year of 86%. Causes of death were pulmonary bronchiolitis obliterans (BOS, n = 1) and graft failure (n = 1). Twenty-two patients had initial donor neutrophil recovery at a median day +14 (range, +11 to +21); for these patients, the median duration of severe neutropenia (ANC < 500/μL) was 7.5 days (range, 4 to 16 days). Of 20 patients who at the time of analysis are ≥ 30 days from HSCT, 18 had platelet engraftment (≥20,000/μL, transfusion unsupported) at a median day +22.5 (range, +10 to +94). One patient developed Grade II aGvHD (haploidentical marrow graft) which was successfully treated; no patients developed Grade III-IV aGvHD. One patient developed chronic GvHD with fatal BOS (UCB). Regimen-related complications were as follows: veno-occlusive disease, n = 0; hemorrhagic cystitis, n = 1; diffuse alveolar hemorrhage n = 1; idiopathic pneumonia syndrome, n = 1; immune-mediated cytopenias, n = 2; CMV viremia, n = 3; and, adenovirus infection, n = 1. Twenty patients (83%) have demonstrated durable, complete donor myeloid engraftment following the regimen. Of these, all have demonstrated mixed donor-recipient T-cell chimerism. Four patients, (all UCB grafts), have experienced graft failure: aplastic graft failure, n = 3, and autologous hematopoietic recovery, n = 1. Three of these patients underwent second HSCT and 2 are alive and engrafted while the other died of complications following second transplant. One patient awaits second transplant. In summary, this regimen of high-exposure, targeted daily busulfan and fludarabine in children with IMD provides favorable engrafted survival with minimal toxicities. Disclosures No relevant conflicts of interest to declare.
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Wamil, Malgorzata, Ruth Andrew, Karen E. Chapman, Jonathan Street, Nicholas M. Morton, and Jonathan R. Seckl. "7-Oxysterols Modulate Glucocorticoid Activity in Adipocytes through Competition for 11β-Hydroxysteroid Dehydrogenase Type." Endocrinology 149, no. 12 (August 28, 2008): 5909–18. http://dx.doi.org/10.1210/en.2008-0420.
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Obesity is associated with an increased risk of diabetes type 2, dyslipidemia, and atherosclerosis. These cardiovascular and metabolic abnormalities are exacerbated by excessive dietary fat, particularly cholesterol and its metabolites. High adipose tissue glucocorticoid levels, generated by the intracellular enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), are also implicated in the pathogenesis of obesity, metabolic syndrome, and atherosclerosis. 11β-HSD1 also interconverts the atherogenic oxysterols 7-ketocholesterol (7KC) and 7β-hydroxycholesterol (7β-HC). Here, we report that 11β-HSD1 catalyzes the reduction of 7KC to 7β-HC in mature 3T3-L1 and 3T3-F442A adipocytes, leading to cellular accumulation of 7β-HC. Approximately 73% of added 7KC was reduced to 7β-HC within 24 h; this conversion was prevented by selective inhibition of 11β-HSD1. Oxysterol and glucocorticoid conversion by 11β-HSD1 was competitive and occurred with a physiologically relevant IC50 range of 450 nm for 7KC inhibition of glucocorticoid metabolism. Working as an inhibitor of 11β-reductase activity, 7KC decreased the regeneration of active glucocorticoid and limited the process of differentiation of 3T3-L1 preadipocytes. 7KC and 7β-HC did not activate liver X receptor in a transactivation assay, nor did they display intrinsic activation of the glucocorticoid receptor. However, when coincubated with glucocorticoid (10 nm), 7KC repressed, and 7β-HC enhanced, glucocorticoid receptor transcriptional activity. The effect of 7-oxysterols resulted from the modulation of 11β-HSD1 reaction direction, and could be ameliorated by overexpression of hexose 6-phosphate dehydrogenase, which supplies reduced nicotinamide adenine dinucleotide phosphate to 11β-HSD1. Thus, the activity and reaction direction of adipose 11β-HSD1 is altered under conditions of oxysterol excess, and could impact upon the pathophysiology of obesity and its complications.
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Markelova, Nadezhda, and Lyudmila Kochetova. "Yury Semyonovich Vinnik - Professor, Honored Worker of Science of the Russian Federation, Honorary Professor of the Federal State Educational Establishment of the Russian Federation "Krasnoyarsk State Medical University named after Professor VF Voyno-Yasenetsky", Ministry of Health of Russia (on the occasion of his 70th birthday)." Vestnik of Experimental and Clinical Surgery 11, no. 1 (April 8, 2018): 80. http://dx.doi.org/10.18499/2070-478x-2018-11-1-80.
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The main field of scientific interests Yu.S. Vinnica - hepato-pancreatic-biliary surgery: acute pancreatitis, reconstructive biliary surgery, pancreatic injury, cholelithiasis and its complications; mechanical jaundice, surgery of the stomach and duodenum, herbiology with the use of reticular endoprostheses, surgery of the large intestine (x-ray endovascular surgery), purulent surgery, diabetic foot, frostbites (questions of the pathogenesis of cold trauma and the treatment of complications), immunodeficiency, cytokinotherapy, metabolic immunotherapy of surgical diseases, peritonitis; syndrome of systemic inflammatory response, use in surgery of new biopolymers - polyhydroxyalkanoates and medical products on their basis. Yu.S. Vinnik is the founder of the scientific school of abdominal and purulent surgery. Under the direction of Vinnik Yu.S. 47 candidate dissertations, 13 doctoral dissertations were defended. He is the author of more than 800 published works, 40 copyright patents of Russia, 37 monographs.
Since 1995, he has been elected to the present time as a full member of the New York Academy of Sciences, since 1996 he has been an academician of the International Academy of Sciences on Ecology, Human and Nature Safety (MANEB), since 1999 - full member of the Russian Academy of Natural Sciences (RANS) since 2000 - Academician of the Russian Academy of Natural Sciences (RANS), Corresponding Member of the Russian Academy of Natural Sciences (RAE), Academician of the Petrovsky Academy of Sciences and Arts (PANI). Honored Doctor of the Russian Federation. Honored Worker of Science and Education of the Russian Federation. Member of the Editorial Board of the journals of the VAK "Annals of Surgical Hepatology", "Bulletin of Experimental and Clinical Surgery", "Surgery News", "Moscow Surgical Journal", "Siberian Medical Review", "Surgical Practice". Member of the Russian Society of Surgeons, the Russian Society of Surgeons-Hepatologists, the Russian Society of Surgeons-Gastroenterologists, the Russian Society of Herniologists, the Association of General Surgeons of the Russian Federation, the Russian Society of Endoscopic Surgeons.
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Rivera Nazario, Ivan Augusto, Arnaldo Nieves Ortiz, Jose Ayala Rivera, Kyomara Hernandez Moya, Arnaldo Rojas, Zahira Marie Lugo Lopez, Marina Torres Torres, et al. "An Atypical Presentation of Hyperosmolar Hyperglycemic State Induced by SARS CoV 2." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A366—A367. http://dx.doi.org/10.1210/jendso/bvab048.746.
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Abstract Hyperglycemic emergencies such as Diabetic Ketoacidosis (DKA) or Hyperosmolar Hyperglycemic State (HHS) are commonly precipitated by infectious processes. Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) is a novel infectious process prompting hyperglycemic crisis. SARS-CoV-2 at the level of the lungs affects ACE2 functioning which in turns decrease the B cells proliferation at the pancreas and hinders insulin secretion. Advanced age and comorbidities such as hypertension, cardiovascular disease and diabetes mellitus are considered to be a risk factors for severe illness and mortality between patients with SARS-CoV-2. We present the case of a 39-year-old woman with medical history of uterine fibroma, who presented with complains of general malaise, polyuria and polydipsia of one week evolution, associated with sore throat, subjective fever, dry cough, abdominal pain, nausea and vomiting. Physical examination remarkable for dry oral mucosa, decreased skin turgor, and prolonged capillary refills. Vital signs significant for hypertension, tachycardia, and tachypnea. Laboratory work up remarkable for glucose of 1321 mg/dL, HCO3- of 16 mEq/L, serum osmolality of 333 mOsm/kg, serum ketones positive and HbA1C of 15%. ABG’s showed pH of 7.33, PCO2 of 29.8 and a PAO2 of 158.5 mmHg for a high anion gap metabolic acidosis (AG of 15.3 mEq/L), non-anion gap metabolic acidosis with respiratory alkalosis. Chest X-ray revealed bilateral perihilar, peribronchial cuffing. SARS-CoV-2 PCR testing was positive. Clinical and laboratory workup met criteria for diagnosis of HHS and Diabetes Mellitus de Novo most likely secondary to SARS-CoV-2 infection. Patient was treated with aggressive IV hydration and insulin infusion with resolution of hyperglycemia, ketonemia and symptoms. SARS-CoV-2 infection can precipitate acute metabolic complications in patients with diabetes or unknown diagnosis of diabetes. The effect of the virus could be direct effect on β-cell function. To our knowledge, there are only a few cases reported of HHS precipitated by SARS-CoV-2 infection therefore medical awareness is important for early diagnosis of possible triggering factors such as COVID-19 and early management of patients presenting with new onset hyperglycemic emergencies.
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Dominguez, Hydelene Beray, Elizabeth P. Pacheco, Cecilia Jimeno, Franceslina C. Lantion-Ang, Edrome Hernandez, and Harold Henrison Chang Chiu. "Recurrent Pheochromocytoma, as Component of Multiple Endocrine Neoplasia." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A1004—A1005. http://dx.doi.org/10.1210/jendso/bvab048.2055.
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Abstract Background: Pheochromocytoma is a rare neuroendocrine tumor from the adrenal medulla’s chromaffin cells that secrete catecholamines. The mainstay of treatment is surgery. Although rare, it has a recurrence rate of 6.5-16.5% even after adequate surgical removal with a notable increase in prevalence among genetic syndromes, extra-adrenal tumors, larger tumor size, and younger age of diagnosis. Case: A 23-year-old Filipino male with no known familial disease presented with episodic headache, palpitations, diaphoresis, and resistant hypertension. Two masses in the left adrenal gland, with the larger one measuring 6.0cm x 5.0cm x 3.0cm, were surgically removed. Histologic examination revealed pheochromocytoma. Post-operatively, there was the normalization of urinary metanephrines and the resolution of the signs and symptoms. He was lost to follow-up and returned five years later with an abdominal ultrasound demonstrating a right adrenal mass. He had no accompanying signs and symptoms; the physical examination was unremarkable. On workup, biochemical testing revealed two 24-hour urinary metanephrine levels were markedly elevated, 14.49 and 19.97 (NV:0-1mg/24 hours). Calcitonin: 644 (NV:0-18pg/ml) and carcinoembryonic antigen (CEA): 23.52 (NV:<5ng/ml) were also elevated. Mild hypercalcemia was noted with elevated intact PTH 101.74 (NV:0-65pg/ml). Parathyroid scintigraphy was normal. The neck ultrasound showed multiple bilateral thyroid nodules, with the largest measuring 1.2cmx0.9cm (TIRADS IV). The abdominal CT scan showed two well-defined, homogenous right adrenal masses, with the largest measuring 6.3cm x 5.6cm x 7.4cm. He underwent right adrenalectomy, and histopathology showed pheochromocytoma with Pheochromocytoma of the Adrenal Scale Score (PASS) of 3. One month later, he underwent total thyroidectomy with neck dissection and inferior parathyroid gland resection. Histopathology confirmed medullary thyroid cancer with nodal metastasis and parathyroid adenoma. The patient recovered well without complications. Biochemical tests normalized eight weeks post-surgery. The presence of synchronous recurrent pheochromocytoma, medullary thyroid cancer (MTC), and primary hyperparathyroidism is consistent with multiple endocrine neoplasia 2A (MEN2A) syndrome. Conclusion: Lifelong follow-up is essential in patients treated for pheochromocytoma despite the complete removal of the adrenal masses due to recurrence risk. Recurrence should likewise raise the suspicion of MEN2, a genetic syndrome. In addition, the pheochromocytoma has malignant characteristics, and the MTC has metastases to the cervical lymph nodes. Early detection and prompt intervention are essential for the treatment of the disease.
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Bagriy, A. E., A. D. Zubov, M. V. Khomenko, E. S. Mikhailichenko, E. A. Pylaeva, N. A. Khaustova, and E. V. Bryukhovetskaya. "Patient Management in Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus." Russian Journal of Gastroenterology, Hepatology, Coloproctology 31, no. 2 (June 2, 2021): 14–26. http://dx.doi.org/10.22416/1382-4376-2021-31-2-14-26.
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Aim. A current overview of non-pharmacological and drug-based approaches to non-alcoholic fatty liver disease (NAFLD) combined with type 2 diabetes mellitus (T2D).Key points. NAFLD is associated with an increased cardiovascular risk (due to association with “metabolic syndrome”) and the risks of liver cirrhosis and hepatocellular carcinoma. Macro- and microvascular complications in T2D comorbidity entail a higher overall mortality. A conjunction of lifestyle change and rational medication strategies to reach the target levels of glycosylated haemoglobin, low-density lipoprotein cholesterol, systolic and diastolic blood pressure is key in management of such patients. A body weight loss by 5–7 % or more (through caloric restriction or a bariatric surgery) promotes a marked reduction in liver fat and even reversal of steatohepatitis. Metered exercise exerts this effect even at insignificant weight loss. Minimising alcohol consumption and smoking is critical. A hepatotropic drug therapy is most essential in moderate fibrotic NAFLD. It includes antidiabetic agents (metformin, thiazolidinediones, glucagon-like peptide-1 receptor agonists, sodium-glucose co-transporter-2 inhibitors), bile acid preparations (e.g., 24-nor-ursodeoxycholic acid), farnesoid X receptor agonists (obeticholic acid, tropifexor), statins, acetylsalicylic acid. Combinations are superior to individual-drug schemes.Conclusion. The management of combined NAFLD-T2D requires a close inter-specialty involvement from hepatology, gastroenterology, endocrinology and cardiology. This interdisciplinary problem can be tackled through persuasive lifestyle recommendations and choosing rational medication strategies with a proved hepatoprotective efficacy.
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Lee, Je-Hwan, Seong-Jun Choi, Jung-Hee Lee, Miee Seol, Keun Hee Kim, Jae-Hoo Park, Hawk Kim, et al. "Standard Induction Followed by Attenuated Consolidation Therapy in Elderly Patients with Acute Myeloid Leukemia." Blood 106, no. 11 (November 16, 2005): 4602. http://dx.doi.org/10.1182/blood.v106.11.4602.4602.
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Abstract Compared to younger patients with acute myeloid leukemia (AML), elderly patients are associated with poorer prognosis and only a few survive long-term. Although several randomized trials demonstrate that elderly patients benefit from full-dose application of cytarabine plus anthracyclines rather than less intensive chemotherapy for induction therapy, optimal post-remission therapy remains to be determined. We performed a prospective phase II multicenter trial of standard induction therapy (7+3 of cytarabine plus daunorubicin) followed by 2 cycles of attenuated consolidation therapy (5+1 of cytarabine plus daunorubicin) for elderly AML patients excluding M3. This study was designed to reduce fatal complications by intensive post-remission therapy, benefits of which have not been evidenced in elderly patients. Induction therapy consisted of cytarabine (200 mg/m2/d x 7) and daunorubicin (45 mg/m2/d x 3). If interim bone marrow examination, which was done at 14 days after the start of induction therapy, showed persistent leukemia, the second attempt of induction therapy was tried with the same doses of cytarabine for 5 days and daunorubicin for 2 days. The patients who attained complete remission (CR) by induction therapy received 2 cycles of attenuated dose consolidation therapy (cytarabine 200 mg/m2/d x 5 plus daunorubicin 45 mg/m2/d x 1). Forty-one patients, 25 males and 16 females, were enrolled into the study between Jan 2002 and Dec 2004. Median age was 66 years (range, 60–78 years). Thirty-seven patients received the planned dose of induction therapy and 4 did not complete it due to intolerance in 3 or tumor lysis syndrome in 1. CR was attained in 16 patients after a first attempt of induction therapy. A second attempt of induction therapy was administered to 16 patients, 8 of whom attained CR. Overall, 24 (58.5%; 95% CI, 43.5–73.6%) of 41 enrolled patients achieved CR at a median of 34 days (range, 21–86 days). In the 17 patients who did not achieve CR, the cause of treatment failure was resistant leukemia in 15, complications of aplasia in 1, and indeterminate in 1. Of 24 CR patients, 17 completed all 2 cycles of consolidation therapy, 3 received 1 cycle, and 4 did not receive consolidation therapy. During induction therapy, most common non-hematologic toxicities (≥ grade 3) were febrile neutropenia (83%) and metabolic abnormalities (44%). During consolidation therapy, non-hematologic toxicities (≥ grade 3) were infrequent except febrile neutropenia (45% for the first consolidation and 41% for the second consolidation). There were no fatal complications during consolidation therapy. After a median follow-up duration of 566 days (range, 63–1190 days) among surviving patients, 27 died and actuarial 3-year overall survival was 17.0%. No patient died in remission. Fifteen of 24 CR patients relapsed and actuarial 3-year disease-free survival was 22.5%. Our study suggests that attenuated consolidation does not compromise the outcomes of elderly AML patients, compared to the results from previous reports using more intensive consolidation therapy.
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Ricardo, Gustavo Piech, Nilza Scalissi, Cristina Bellotti Formiga Bueno, Renata Da Cunha Scalco, and Jose Viana Lima. "Non-Functioning Pheochromocytoma in a Patient With Von Hippel Lindau Syndrome (VHL): Case Report." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A1002. http://dx.doi.org/10.1210/jendso/bvab048.2050.
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Abstract Background: We report the case of a patient with VHL Syndrome with an adrenal lesion compatible with non-functioning pheochromocytoma and it’s diagnostic management. Case Report: JMN, female, 32 years old, referred for screening for VHL syndrome, after diagnosis in a sister, who has clear cell renal carcinoma (ccRCC), cerebellar hemangioblastoma and genetic analysis, by next generation sequencing (NGS), which identified the allelic variant germline pathogenic c. 256C> T in heterozygosis in exon 1 of the VHL gene. The patient is asymptomatic and her physical examination is normal. Optic fundus examination with lesion suggestive of right hemangioblastoma. Family history: mother who died at 59 with a diagnosis of ccRCC, without genetic investigation. Maternal aunt diagnosed with VHL and involvement of the cerebellum, kidney and pancreas. Two brothers with genetic and clinical diagnosis of VHL syndrome, presenting pheochromocytoma and renal carcinoma. Laboratory tests: plasma metanephrine: 0.3 nmol/L (RV <0.5nmol/L), plasma normetanephrine: 0.5 nmol/L (RV <0.9nmol/L), chromogranin A 61 ng/mL (RV <93 ng/ml). Genetic evaluation by NGS identified the pathogenic variant c. 256C> T in heterozygosity in exon 1 of the VHL gene. Topographic examinations: magnetic resonance imaging (MRI) of adrenals with nodule in the left adrenal gland, hypersignal in T2, measuring 2.9 x 2.3 cm, suggestive of pheochromocytoma and whole body scintigraphy with metaiodobenzylguanidine (MIBG) positive in the left adrenal gland. She underwent resection of the tumor in the left adrenal, without complications. Anatomopathology compatible with pheochromocytoma with immunohistochemistry for ki67 <3%. Currently, the patient is clinically stable and with periodic follow-up, as well as family members, performing screening for diseases associated with VHL. Conclusion: VHL syndrome is one of the possible causes of non-functioning pheochromocytomas and paragangliomas, and adrenal lesions with negative metanephrine levels do not exclude them; thus highlighting the importance of exams such as CT or MRI and functional topographic studies (whole body scintigraphy with MIBG and / or PETCT with Galio68DOTA) for their diagnosis.
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Mechanick, Jeffrey I., Caroline Apovian, Stacy Brethauer, W. Timothy Garvey, Aaron M. Joffe, Julie Kim, Robert F. Kushner, et al. "CLINICAL PRACTICE GUIDELINES FOR THE PERIOPERATIVE NUTRITION, METABOLIC, AND NONSURGICAL SUPPORT OF PATIENTS UNDERGOING BARIATRIC PROCEDURES – 2019 UPDATE: COSPONSORED BY AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS/AMERICAN COLLEGE OF ENDOCRINOLOGY, THE OBESITY SOCIETY, AMERICAN SOCIETY FOR METABOLIC & BARIATRIC SURGERY, OBESITY MEDICINE ASSOCIATION, AND AMERICAN SOCIETY OF ANESTHESIOLOGISTS." Endocrine Practice 25, Supplement 2 (December 2019): 1–75. http://dx.doi.org/10.4158/gl-2019-0406.
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Objective: The development of these updated clinical practice guidelines (CPGs) was commissioned by the American Association of Clinical Endocrinologists (AACE), The Obesity Society, American Society of Metabolic and Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists Boards of Directors in adherence with the AACE 2017 protocol for standardized production of CPGs, algorithms, and checklists. Methods: Each recommendation was evaluated and updated based on new evidence from 2013 to the present and subjective factors provided by experts. Results: New or updated topics in this CPG include: contextualization in an adiposity-based chronic disease complications-centric model, nuance-based and algorithm/checklist-assisted clinical decision-making about procedure selection, novel bariatric procedures, enhanced recovery after bariatric surgery protocols, and logistical concerns (including cost factors) in the current health-care arena. There are 85 numbered recommendations that have updated supporting evidence, of which 61 are revised and 12 are new. Noting that there can be multiple recommendation statements within a single numbered recommendation, there are 31 (13%) Grade A, 42 (17%) Grade B, 72 (29%) Grade C, and 101 (41%) Grade D recommendations. There are 858 citations, of which 81 (9.4%) are evidence level (EL) 1 (highest), 562 (65.5%) are EL 2, 72 (8.4%) are EL 3, and 143 (16.7%) are EL 4 (lowest). Conclusion: Bariatric procedures remain a safe and effective intervention for higher-risk patients with obesity. Clinical decision-making should be evidence based within the context of a chronic disease. A team approach to perioperative care is mandatory, with special attention to nutritional and metabolic issues. Abbreviations: A1C = hemoglobin A1c; AACE = American Association of Clinical Endocrinologists; ABCD = adiposity-based chronic disease; ACE = American College of Endocrinology; ADA = American Diabetes Association; AHI = Apnea-Hypopnea Index; ASA = American Society of Anesthesiologists; ASMBS = American Society of Metabolic and Bariatric Surgery; BMI = body mass index; BPD = biliopancreatic diversion; BPD/DS = biliopancreatic diversion with duodenal switch; CI = confidence interval; CPAP = continuous positive airway pressure; CPG = clinical practice guideline; CRP = C-reactive protein; CT = computed tomography; CVD = cardiovascular disease; DBCD = dysglycemia-based chronic disease; DS = duodenal switch; DVT = deep venous thrombosis; DXA = dual-energy X-ray absorptiometry; EFA = essential fatty acid; EL = evidence level; EN = enteral nutrition; ERABS = enhanced recovery after bariatric surgery; FDA = U.S. Food and Drug Administration; G4GAC = Guidelines for Guidelines, Algorithms, and Checklists GERD = gastroesophageal reflux disease; GI = gastrointestinal; HCP = health-care professional(s); HTN = hypertension; ICU = intensive care unit; IGB = intragastric balloon(s); IV = intravenous; LAGB = laparoscopic adjustable gastric band; LAGBP = laparoscopic adjustable gastric banded plication; LGP = laparoscopic greater curvature (gastric) plication; LRYGB = laparoscopic Roux-en-Y gastric bypass; LSG = laparoscopic sleeve gastrectomy; MetS = metabolic syndrome; NAFLD = nonalcoholic fatty liver disease; NASH = nonalcoholic steatohepatitis; NSAID = nonsteroidal anti-inflammatory drug; OA = osteoarthritis; OAGB = one-anastomosis gastric bypass; OMA = Obesity Medicine Association; OR = odds ratio; ORC = obesity-related complication(s); OSA = obstructive sleep apnea; PE = pulmonary embolism; PN = parenteral nutrition; PRM = pulmonary recruitment maneuver; RCT = randomized controlled trial; RD = registered dietician; RDA = recommended daily allowance; RYGB = Roux-en-Y gastric bypass; SG = sleeve gastrectomy; SIBO = small intestinal bacterial overgrowth; TOS = The Obesity Society; TSH = thyroid-stimulating hormone; T1D = type 1 diabetes; T2D = type 2 diabetes; VTE = venous thromboembolism; WE = Wernicke encephalopathy; WHO = World Health Organization
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Teles, Luís. "Erdheim-Chester Disease: Case Report with Aggressive Multiple Organ Manifestations." Biomedical Research and Clinical Reviews 1, no. 1 (May 6, 2020): 01–03. http://dx.doi.org/10.31579/2692-9406/002.
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Erdheim-Chester disease (ECD) is a rare non-Langerhans cell, lipid-laden histiocytosis with specific histological and radiological findings. The diagnosis sometimes is established lately in the course of the disease. We present a case of a 64-year-old female with elevated inflammatory markers for one year and symptoms related with her comorbidities, particularly bone pain and short of breath. Past medical history includes a stage III chronic kidney disease, central diabetes diagnosed when she was 38 years old, Paget Disease, metabolic syndrome and ischemic cardiopathy. Computed tomography in the near past showed a tissue densification in the thoracic vertebral column and kidneys with hairy aspect. X-ray of the arms, legs, skullcap, and demonstrated sclerotic changes. F-fluorodeoxyglucose positron emission tomography showed uptake in the skull, mediastinum, abdomen and long bones from arms and legs. Biopsy of the hairy kidney was consent after 4 years of an unknown disease in progression. Histological findings of the biopsy reported a diffuse infiltration by foamy histiocytes. On immunohistochemical staining, the histiocytes were positive for CD68 and negative for CD1 and S100. Mutation of BRAF V600E was present and ECD was established. Tocilizumab was initiated off label due to psychiatric contra indication for interferon use and no clinical conditions for BRAF inhibitors and symptoms started being controlled. The diagnosis of ECD is usually challenging due to the rarity of the disease and clinical overlapping with many other conditions. The rarity and variable presentation of this disease usually leads to delayed diagnosis and to high morbidity and mortality rates from associated complications.
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Sinenchenko, A. G., A. N. Lodyagin, B. V. Batotsyrenov, and O. L. Balabanova. "Epidemiology of acute poisonings with gammahydroxybutyric acid in Saint Petersburg (according to data of a multidisciplinary hospital)." Toxicological Review, no. 2 (May 5, 2021): 33–40. http://dx.doi.org/10.36946/0869-7922-2021-2-33-40.
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It was found that for the period from X.2017 to III.2020 among patients admitted to a multidisciplinary hospital with acute poisoning with narcotic drugs (NV) and psychoactive substances (PAS), persons in whose biological environment GHB was detected ranged from 20,1 to 40,1%. The prevalence of acute poisoning of the studied class in male patients (86%) of working age (the average age was 34,2 ± 2,9 year) was proved. The patients used 1,4-butanediol (1,4-BD) as a toxicant (GHB) in 95% of cases. The dynamics of the incidence of acute GHB poisoning over a three-year period was uneven, with peaks of maximum values in August (Me = 168), March (Me = 90), and September (Me = 103) and low rates - in June (Me = 71) and total upward trend - y = 6,6573x = 343,23, R2 = 0,053. The severity of acute GHB poisoning at the time of admission on the PSS scale was 2,2 ± 0,57 points, PSSSP – 22,7 ± 2,17 points. Acute GHB poisoning was characterized by signs of toxic-hypoxic encephalopathy, clinically manifested in the form of depression of consciousness to the level of deep stunning - coma. The duration of inpatient treatment of patients was (1,76 ± 3,7, min = 1, max = 35) days, the period of stay in the intensive care unit (ICU) was 4,2 ± 0,4 hours. The increase in hospitalization (more than a day) was due to somatic complications of acute poisoning (nasocomial pneumonia, systemic rhabdomyolysis, acute renal failure) - in 14% of cases, severe withdrawal syndrome with delirious confusion - in 3,5% of cases. The post-intoxication period was characterized by moderate withdrawal symptoms – 13,7 ± 2,1 points, according to the CIWA-Ar scale. The delirious syndrome was characterized by a protracted course (9,5 ± 1,2 days), an atypical clinical picture, and metabolic disorders. The mortality rate due to acute GHB poisoning increased from 0,09 to 0,22%, in 2019 the cause of death was pronounced degenerative changes in internal organs and varying degrees of severity of microcirculation disorders.
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Gomez-Duarte, Oscar G. "Metabolic Syndrome and General Anesthesia Complications." Colombian Journal of Anesthesiology 40, no. 2 (May 2012): 95–97. http://dx.doi.org/10.1016/s2256-2087(12)70019-6.
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VOYAKI, S., A. EFSTRATOPOULOS, A. BALTAS, L. MOURGOS, and A. STAVRIANOU. "Hypertensive complications associated with metabolic syndrome." American Journal of Hypertension 18, no. 5 (May 2005): A169—A170. http://dx.doi.org/10.1016/j.amjhyper.2005.03.470.
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Mishchenko, V. P., I. V. Shpak, I. V. Rudenko, V. V. Mishchenko, T. Y. Moskalenko, I. L. Golovatyuk-Józefpolska, M. Y. Golubenko, and A. S. Makoshyba. "Features of the postcovid period in women in labor." REPRODUCTIVE ENDOCRINOLOGY, no. 59 (July 22, 2021): 46–50. http://dx.doi.org/10.18370/2309-4117.2021.59.46-50.
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Clinical manifestations in the abdominal cavity of a woman in labor, discovered during an urgent cesarean section at 41 weeks of gestation 2 months after an acute form of COVID-19, are described. The materials of medical documentation were analyzed and the features of the course of pregnancy by trimester, urgent cesarean section, postoperative period, laboratory parameters, ultrasound data, cardiotocography, fetal condition at birth and three days later were determined.Presentation of case. 33-year-old pregnant woman (pregnant for the first time) had COVID-19 at 26 weeks of gestation. At a cesarean section for urgent indications at 41 weeks of gestation during the revision of the abdominal cavity was found that the visceral peritoneum of the uterus along the anterior and posterior surfaces, fallopian tubes, wide and round uterus ligaments, ovaries and parietal peritoneum of the pelvis, areas of the serous intestinal layer were with expressive signs of edema covered with vesicular rash, in places in the conglomerate, which were bleeding. There was no abdominal effusion.The child was born with 7–8 points Apgar score and had a negative PCR result for COVID-19. Placenta measuring 25 x 21 x 5.0 x 0.5 cm with multiple petrification, single red heart attacks. The shells are distinctly yellow-gray-green in color. The umbilical cord is 70 cm long and usual color. Amniotic fluid is clear. The early and late postoperative periods and the postpartum period proceeded without complications. At once the disorders in the blood coagulation system, immune system, positive COVID-19 IgG and IgM were identified in mother. Videin, Magniсum-antistress, preparations of acetylsalicylic acid and for the comprehensive support of the physiological state of the intestine were used in the complex treatment of the postpartum period.Conclusion. COVID-19 disease is pathology with many unknowns. Therefore, each clinical observation is important for studying of its course. Post-COVID syndrome and long-COVID syndrome have individual characteristics. Collective experience will contribute to the definition of an algorithm for the therapy of patients and personalized dispensary observation after an acute period.
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Ahmed, Qanta A. "Metabolic Complications of Obstructive Sleep Apnea Syndrome." American Journal of the Medical Sciences 335, no. 1 (January 2008): 60–64. http://dx.doi.org/10.1097/maj.0b013e31815f2c1a.
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Tesauro, Manfredi, Micaela Iantorno, and Umberto Campia. "Obesity-Related Metabolic Syndrome and Vascular Complications." International Journal of Endocrinology 2013 (2013): 1–2. http://dx.doi.org/10.1155/2013/534056.
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Panjawatanan, Panadeekarn, Samir Jha, Joseph Hughes, and Erik Riesenfeld. "A Case of Concomitant COVID-19 Infection-Induced Acute Respiratory Distress Syndrome and Diabetic Ketoacidosis: Another Challenge in Fluid Management." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A357. http://dx.doi.org/10.1210/jendso/bvab048.727.
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Abstract Background: Coronavirus Disease 2019 (COVID-19) has been announced as a pandemic worldwide. The respiratory tract is a target organ-system which can result in serious complications like acute respiratory distress syndrome (ARDS). Management of this condition is more challenging in diabetes who developed diabetic ketoacidosis (DKA). Clinical Case: We report a case of a 59-year-old male who presented with 4 days of productive cough with blood-tinged sputum, shortness of breath, and chills. Patient had decreased oral intake and had not been compliant with his medication. He had underlying disease significant for type 2 diabetes, essential hypertension, obesity (BMI 32 kg/m2), history of pancreatitis and diabetic ketoacidosis. His diabetes medications included insulin degludec 126 units with insulin lispro sliding scale, dulaglutide, metformin, and sitagliptin. On examination, the patient was lethargic. Initial vital signs included a temperature of 36.8°C, respiratory rate 24/min, heart rate 65 bpm, BP 140/67 mmHg, and oxygen saturation 91% on room air. Lung auscultation revealed bilateral widespread crackles. Laboratory was significant for glucose 387 mg/dL (70–139), pH 7.25 (7.35-7.28), anion gap 15.8 mEq/L (6–14) and concurrent normal gap acidosis, urine ketones 15 mg/dL (negative), and LDH 325 U/L (140–171). An initial chest x-ray showed bilateral peripheral pulmonary infiltrates. Workup was negative for influenza, pneumococcus, and legionella. The patient was subsequently intubated on the first day for worsening hypoxia due to severe ARDS (PaO2/FiO2 ratio of 71). He was concomitantly treated for DKA and hypotension with intravenous insulin, initially started at 12 units/hour with subsequent titration down to average of 5 units/hour, fluid resuscitation (approximate 34 ml/kg actual body weight) and, potassium repletion on the first day. On the same day, his hypoxia worsened with an increase in pulmonary infiltrates, so we stopped intravenous fluids and initiated norepinephrine for 24 hours. His mechanical ventilation settings followed ARDS guidelines. Positive COVID-19 was detected from real-time RT-PCR. After maintaining a negative fluid balance, we were able to extubate in 72 hours. Intravenous insulin was continued for 46 hours then was switched to subcutaneous basal-bolus regimen. He was discharged with insulin degludec 100 units with insulin lispro sliding scale, metformin, and sitagliptin. Dulaglutide was held. Conclusion: Type 2 diabetes are rarely affected by DKA but can be found in up to 27% of the cases. There are reports of ARDS as a serious complication in severe DKA in adults and children, yet no data for concomitant DKA and ARDS has been published. We propose that the management of DKA in COVID-19 patients with ARDS may be similar to the paradigm utilized for other volume restriction in patients with congestive heart failure and end-stage renal failure.
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Cheng, Tsung O. "The metabolic syndrome, formerly called metabolic “Syndrome X”." American Journal of Cardiology 94, no. 1 (July 2004): 148–49. http://dx.doi.org/10.1016/j.amjcard.2004.03.019.
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Khromilev, A. V. "Metabolic syndrome and pregnancy." Obesity and metabolism 11, no. 2 (June 15, 2014): 3–7. http://dx.doi.org/10.14341/omet201423-7.
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Metabolic syndrome (MS) is a major problem of public health and health care system, with rising prevalence in the world. There is evidence that obesity, as the main component of MS, is strongly associated with the presence of gestational complications: fetal growth retardation, fetal macrosomia, gestational diabetes, preeclampsia, preterm delivery, stillbirth and perinatal death. The underlying mechanisms of this association are actively investigated nowadays. The importance of MS in pregnancy is also determined by the increase of the risk of venous trombosis.
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Altieri, Pablo I., Yolanda Figueroa, Héctor L. Banchs, José Hernández-Gil de Lamadrid, Nelson Escobales, and María J. Crespo. "Metabolic syndrome in an Hispanic population–cardiovascular complications." QScience Connect, no. 2011 (November 2011): 5. http://dx.doi.org/10.5339/connect.2011.5.
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Millichap, J. Gordon. "Metabolic Complications of Antipsychotic Therapy for Tourette Syndrome." Pediatric Neurology Briefs 24, no. 7 (July 1, 2010): 54. http://dx.doi.org/10.15844/pedneurbriefs-24-7-8.
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Restivo, Ignazio, Alessandro Attanzio, Luisa Tesoriere, and Mario Allegra. "Suicidal Erythrocyte Death in Metabolic Syndrome." Antioxidants 10, no. 2 (January 21, 2021): 154. http://dx.doi.org/10.3390/antiox10020154.
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Eryptosis is a coordinated, programmed cell death culminating with the disposal of cells without disruption of the cell membrane and the release of endocellular oxidative and pro-inflammatory milieu. While providing a convenient form of death for erythrocytes, dysregulated eryptosis may result in a series of detrimental and harmful pathological consequences highly related to the endothelial dysfunction (ED). Metabolic syndrome (MetS) is described as a cluster of cardiometabolic factors (hyperglycemia, dyslipidemia, hypertension and obesity) that increases the risk of cardiovascular complications such as those related to diabetes and atherosclerosis. In the light of the crucial role exerted by the eryptotic process in the ED, the focus of the present review is to report and discuss the involvement of eryptosis within MetS, where vascular complications are utterly relevant. Current knowledge on the mechanisms leading to eryptosis in MetS-related conditions (hyperglycemia, dyslipidemia, hypertension and obesity) will be analyzed. Moreover, clinical evidence supporting or proposing a role for eryptosis in the ED, associated to MetS cardiovascular complications, will be discussed.
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Wang, Ally W., Yan Yan Sally Xie, and Khadeen C. Cheesman. "Excellent Maternal and Fetal Outcomes Associated With Early Detection and Treatment of Cushing’s Syndrome During Pregnancy." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A131. http://dx.doi.org/10.1210/jendso/bvab048.264.
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Abstract Background: Despite its relative high prevalence in women of reproductive age, pregnancy is uncommon in Cushing’s syndrome (CS) as hypercortisolism typically results in anovulation and infertility. Early diagnosis and treatment are essential to reduce maternal and fetal complications. Clinical Case: A 31-year-old woman with Type 2 diabetes mellitus and hypertension was referred for significantly elevated midnight salivary and urine cortisol levels consistent with CS. Six months after initial laboratory findings, she presented to our endocrinology clinic eight weeks pregnant with di/di twins. She reported worsening blood pressure and glucose control, mood fluctuations, and easy bruising for the past several months. Menses were regular prior to conception. Physical exam was notable for round facies, mild dorsal hump, and supraclavicular fullness. Lab tests at eight and thirteen weeks gestation respectively showed: elevated 24-hr urine free cortisol 368.5 and 597.5 ug/24hr (< 45); elevated midnight salivary cortisol 0.88 mcg/dL (<0.09) at eight weeks; ACTH <1.1 and 8.1 pg/mL (7.2 - 63.3); and elevated morning cortisol 34.2 and 36 ug/dL (6.2 - 19.4). Her hemoglobin A1C was 8.1% on metformin and Levemir. Pituitary MRI was normal. MRI of the abdomen without contrast demonstrated a 2.5 x 3.5 cm solid homogeneous mass in the right adrenal gland. The patient underwent successful right adrenalectomy at seventeen weeks gestation and was discharged on glucocorticoid replacement. Glucose control was labile due to non-compliance but otherwise the remainder of her pregnancy was uncomplicated. The patient delivered healthy twins at thirty-five weeks. At six months postpartum she is doing well on low dose hydrocortisone replacement. Most recent hemoglobin A1C was 5.7% without diabetes medication. Conclusion: There is no consensus on the management of CS during pregnancy due to the rarity of this condition. CS in pregnancy is associated with high maternal and fetal morbidity and mortality, thus early diagnosis and prompt treatment is essential. Our case demonstrates the importance of discussing contraception with Cushing’s patients of reproductive age. It also adds to prior studies and showed that when treated early in pregnancy, either surgically or medically, maternal and fetal risks such as uncontrolled diabetes and fetal loss are significantly reduced. The ideal management of these patients is an area of ongoing investigation.
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Cairo, Mitchell S., Stephen Thompson, Krishna Tangirala, and Michael T. Eaddy. "Costs and Outcomes Associated with Rasburicase Versus Allopurinol in Patients with Tumor Lysis Syndrome." Blood 120, no. 21 (November 16, 2012): 3175. http://dx.doi.org/10.1182/blood.v120.21.3175.3175.
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Abstract Abstract 3175 Background: Tumor lysis syndrome (TLS) is an oncologic emergency resulting in several metabolic abnormalities (Cairo et al, BJH, 2004). Hyperuricemia and its associated complications are the most frequent manifestations of TLS. For decades, treatment has consisted of hydration, urine alkalinization, and administration of allopurinol (Cairo et al BJH, 2011). However, recent clinical trials have shown that initiation of rasburicase, a hypouricemic agent, within four hours significantly reduces high uric acid (UA) levels in patients experiencing TLS (Goldman et al Blood, 2001). Studies demonstrate that rasburicase is safe and effective, has excellent tolerability, and is potentially cost-effective in patients at high risk for TLS. Objective: The objective of this retrospective analysis was to evaluate real-world differences in UA levels, length of stay and costs for patients initiating treatment with rasburicase compared to patients receiving allopurinol. Methods: A retrospective study, spanning January 1, 2005 to March 31, 2009, was conducted utilizing administrative data from more than 400 U.S. hospitals. Hospitalized patients with clinically confirmed TLS, who received rasburicase or allopurinol during the study period were eligible for inclusion. Patients with a diagnosis of gout, as determined by the presence of an ICD-9 diagnosis code 274.x, were excluded from the study. Patients receiving rasburicase were propensity score matched to allopurinol-treated patients in a 1:4 ratio based on time between hospital admission and treatment initiation, baseline UA level, cancer type, age, gender, race, hospital characteristics, payer type, and prior intensive-care unit (ICU) admission. Differences in length of stay (LOS), changes in UA levels and serum creatinine, days in the ICU, and costs per percent of UA reduction were assessed through various statistical models. Due to a high level of missing cancer diagnosis, comparative results of rasburicase and allopurinol were also evaluated through sensitivity analysis to test the robustness of the results. Results: A total of 130 patients were identified, matched and included in this study; 26 initiated treatment with rasburicase and 104 were treated with allopurinol. Patients were predominately male (∼61%) Caucasian (∼76%) with an average age of 55 years. There were no statistically significant differences among baseline variables between the two cohorts. Prior to initiating treatment, mean UA levels were 11.4 mg/dL for the rasburicase cohort and 11.2 mg/dL for allopurinol cohort. By the second day of treatment mean UA levels were 5.3 mg/dL (p<0.0001) lower for rasburicase (2.7mg/dL) compared to allopurinol (8.0 mg/dL). Changes in potassium, phosphorus and creatinine levels were not statistically different across the two cohorts. The LOS for patients in the rasburicase cohort averaged 11.5 days compared to 16.5 days for allopurinol patients (p=0.0212); rasburicase patients also had a lower ICU LOS, 1.4 and 3.9 days, respectively (p<0.0001). The reduction in LOS correlated with a reduction in costs, which averaged $34,065 per rasburicase patient compared to $54,103 per allopurinol patient (p=0.0205). Results of the sensitivity analyses did not change the overall findings. Conclusions: This retrospective study, using hospital administrative data, revealed that treatment with rasburicase, compared with allopurinol, was associated with a significant reduction in UA levels, ICU LOS, overall LOS and overall costs per patient. Despite the increase pharmaceutical costs of rasburicase versus allopurinol, the use of rasburicase in patients with TLS is cost effective and reduces LOS. Disclosures: Cairo: sanofi aventis: Consultancy. Thompson:sanofi aventis: Employment. Tangirala:sanofi aventis: Employment. Eaddy:Xcenda: Employment.
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Il’ina, I. Yu. "Specificities of the treatment for polycystic ovary syndrome and metabolic syndrome." Russian Journal of Woman and Child Health 3, no. 4 (2020): 254–59. http://dx.doi.org/10.32364/2618-8430-2020-3-4-254-259.
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This paper discusses polycystic ovary syndrome (PCOS), a common endocrine disorder characterized by hirsutism, anovulation, and polycystic ovaries. Insulin resistance which is considered the major causative factor for both PCOS and metabolic syndrome is emphasized. The early diagnosis of metabolic disorders which increase the risk of cardiovascular complications and the complications of pregnancy (including gestational diabetes and hypertension which may result in preeclampsia and placental abruption) is of particular importance. The presence of metabolic syndrome in PCOS is associated with poor prognosis in terms of fertility and has a negative impact on the outcomes of in vitro fertilization in infertile women with PCOS. When describing treatment approaches, the role of metformin, inositol, folates, vitamin D, and statins in treating metabolic disorders in PCOS and metabolic syndrome, reducing the risks of cardiovascular complications, and realizing fertile function is highlighted. The course of PCOS is complicated by psychic disorders (i.e., depression, anxiety, bipolar disorder, or eating disorders) which are common in these women and should be considered when prescribing medications. KEYWORDS: polycystic ovary syndrome, insulin resistance, infertility, metabolic syndrome, cardiovascular complications, inositol, folates. FOR CITATION: Il’ina I.Yu. Specificities of the treatment for polycystic ovary syndrome and metabolic syndrome. Russian Journal of Woman and Child Health. 2020;3(4):254–259. DOI: 10.32364/2618-8430-2020-3-4-254-259.
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Cheng, Tsung O. "Cardiac syndrome X versus metabolic syndrome X." International Journal of Cardiology 119, no. 2 (July 2007): 137–38. http://dx.doi.org/10.1016/j.ijcard.2006.06.062.
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