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Kraut J.A.,Veterans Administration Greater Los Angeles VHAGLA | Madias N.E.,St Elizabeths Medical Center
Nature Reviews Nephrology | Year: 2010

Metabolic acidosis is characterized by a primary reduction in serum bicarbonate (HCO3- ) concentration, a secondary decrease in the arterial partial pressure of carbon dioxide (PaCO2) of ∼ 1 mmHg for every 1 mmol/l fall in serum HCO 3 concentration, and a reduction in blood pH. Acute forms (lasting minutes to several days) and chronic forms (lasting weeks to years) of the disorder can occur, for which the underlying cause/s and resulting adverse effects may differ. Acute forms of metabolic acidosis most frequently result from the overproduction of organic acids such as ketoacids or lactic acid; by contrast, chronic metabolic acidosis often reflects bicarbonate wasting and/or impaired renal acidification. The calculation of the serum anion gap, calculated as [Na + ]- ([HCO 3- ] + [Cl - ]), aids diagnosis by classifying the disorders into categories of normal (hyperchloremic) anion gap or elevated anion gap. These categories can overlap, however. Adverse effects of acute metabolic acidosis primarily include decreased cardiac output, arterial dilatation with hypotension, altered oxygen delivery, decreased ATP production, predisposition to arrhythmias, and impairment of the immune response. The main adverse effects of chronic metabolic acidosis are increased muscle degradation and abnormal bone metabolism. Using base to treat acute metabolic acidosis is controversial because of a lack of definitive benefit and because of potential complications. By contrast, the administration of base for the treatment of chronic metabolic acidosis is associated with improved cellular function and few complications. © 20 Macmillan Publishers Limited. 10 All rights reserved.


Adrogue H.J.,Baylor College of Medicine | Adrogue H.J.,Veterans Affairs Medical Center | Madias N.E.,Tufts University | Madias N.E.,St Elizabeths Medical Center
Journal of the American Society of Nephrology | Year: 2012

Treatment of hypotonic hyponatremia often challenges clinicians on many counts. Despite similar serum sodium concentrations, clinical manifestations can range from mild to life threatening. Some patients require active management, whereas others recover without intervention. Therapeutic measures frequently yield safe correction, yet the same measures can result in osmotic demyelination. To address this challenge, we present a practical approach to managing hyponatremia that centers on two elements: a diagnostic evaluation directed at the pathogenesis and putative causes of hyponatremia, the case-specific clinical and laboratory features, and the associated clinical risk; and a management plan tailored to the diagnostic findings that incorporates quantitative projections of fluid therapy and fluid losses on the patient's serum sodium, balances potential benefits and risks, and emphasizes vigilant monitoring. These principles should enable the clinician to formulate a management plan that addresses expeditiously three critical questions: Which of the determinants of the serum sodium are deranged and what is the underlying culprit? How urgent is the need for intervention? What specific therapy should be instituted and which are the associated pitfalls? Copyright © 2012 by the American Society of Nephrology.


Chapple C.R.,Royal Hallamshire Hospital | Kaplan S.A.,Cornell University | Mitcheson D.,St Elizabeths Medical Center | Klecka J.,University Hospital Plzen | And 4 more authors.
European Urology | Year: 2013

Background: Despite several antimuscarinic treatment options for overactive bladder (OAB), there is still a need for distinct treatment approaches to manage this condition. Mirabegron, a β3-adrenoceptor agonist, has demonstrated efficacy and tolerability for up to 12 wk in phase 3 trials. Objective: To assess the 12-mo safety and efficacy of mirabegron. Design, setting, and participants: Patients ≥18 yr of age with OAB symptoms for ≥3 mo. Interventions: After a 2-wk single-blind placebo run-in, patients with eight or more micturitions per 24 h and three or more urgency episodes in a 3-d micturition diary were randomized 1:1:1 to once-daily mirabegron 50 mg, mirabegron 100 mg, or tolterodine extended release (ER) 4 mg for 12 mo. Outcome measurements and statistical analysis: Primary variable: incidence and severity of treatment-emergent AEs (TEAEs). Secondary variables: change from baseline at months 1, 3, 6, 9, and 12 in key OAB symptoms. Results and limitations: A total of 812, 820, and 812 patients received mirabegron 50 mg, mirabegron 100 mg, and tolterodine ER 4 mg, respectively. Baseline demographic and OAB characteristics were similar across groups. TEAEs were reported in 59.7%, 61.3%, and 62.6% of patients, respectively; most were mild or moderate. Serious TEAEs were reported in 5.2%, 6.2%, and 5.4% of patients, respectively. The most common TEAEs were similar across groups. Dry mouth was reported by 2.8%, 2.3%, and 8.6% of patients, respectively. Adjusted mean changes from baseline to final visit in morning systolic blood pressure were 0.2, 0.4, and -0.5 mm Hg for mirabegron 50 mg, 100 mg, and tolterodine ER 4 mg, respectively. Mirabegron and the active control, tolterodine, improved key OAB symptoms from the first measured time point of 4 wk, and efficacy was maintained throughout the 12-mo treatment period. The study was not placebo controlled, which was a limitation. Conclusions: The safety and tolerability of mirabegron was established over 1 yr, with sustained efficacy observed over this treatment period. Trial registration: ClinicalTrials.gov identifier: NCT00688688. © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.


Kraut J.A.,Medical and Research Services | Kraut J.A.,University of California at Los Angeles | Kraut J.A.,Veterans Affairs Greater Los Angeles Healthcare System | Madias N.E.,St Elizabeths Medical Center | Madias N.E.,Tufts University
New England Journal of Medicine | Year: 2014

Lactic acidosis results from the accumulation of lactate and protons in the body fluids and is often associated with poor clinical outcomes. The effect of lactic acidosis is governed by its severity and the clinical context. Mortality is increased by a factor of nearly three when lactic acidosis accompanies low-flow states or sepsis,1 and the higher the lactate level, the worse the outcome.2 Although hyperlactatemia is often attributed to tissue hypoxia, it can result from other mechanisms. Control of the triggering conditions is the only effective means of treatment. However, advances in understanding its pathophysiological features and the factors causing cellular dysfunction in the condition could lead to new therapies. This overview of lactic acidosis emphasizes its pathophysiological aspects, as well as diagnosis and management. We confine our discussion to disorders associated with accumulation of the l optical isomer of lactate, which represent the vast majority of cases of lactic acidosis encountered clinically. Copyright © 2014 Massachusetts Medical Society.


Gorson K.C.,St Elizabeths Medical Center
Therapeutic Advances in Neurological Disorders | Year: 2012

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune mediated disorder of the peripheral nervous system with clinical features that include weakness, sensory loss, imbalance, pain and impaired ambulation which may lead to substantial disability. This review highlights current treatment strategies for CIDP, how best to utilize proven therapies such as intravenous immunoglobulin, oral prednisone, pulse dexamethasone, and plasma exchange, and when and how to use alternative immunosuppressive agents when first-line therapies are ineffective or poorly tolerated. © 2012 The Author(s).


Picel A.C.,University of California at San Diego | Kansal N.,St Elizabeths Medical Center
American Journal of Roentgenology | Year: 2014

OBJECTIVE. Lifelong postprocedural imaging surveillance is necessary after endovascular abdominal aortic aneurysm repair (EVAR) to assess for complications of endograft placement, as well as device failure and continued aneurysm growth. Refinement of the surveillance CT technique and development of ultrasound and MRI protocols are important to limit radiation exposure. CONCLUSION. A comprehensive understanding of EVAR surveillance is necessary to identify life-threatening complications and to aid in secondary treatment planning. © American Roentgen Ray Society.


Skef W.,St Elizabeths Medical Center | Hamilton M.J.,Harvard University | Arayssi T.,Cornell College
World Journal of Gastroenterology | Year: 2015

Behçet's disease (BD) is an idiopathic, chronic, relapsing, multi-systemic vasculitis characterized by recurrent oral and genital aphthous ulcers, ocular disease and skin lesions. Prevalence of BD is highest in countries along the ancient silk road from the Mediterranean basin to East Asia. By comparison, the prevalence in North American and Northern European countries is low. Gastrointestinal manifestations of Behçet's disease are of particular importance as they are associated with significant morbidity and mortality. Although ileocecal involvement is most commonly described, BD may involve any segment of the intestinal tract as well as the various organs within the gastrointestinal system. Diagnosis is based on clinical criteria - there are no pathognomonic laboratory tests. Methods for monitoring disease activity on therapy are available but imperfect. Evidence-based treatment strategies are lacking. Different classes of medications have been successfully used for the treatment of intestinal BD which include 5-aminosalicylic acid, corticosteroids, immunomodulators, and anti-tumor necrosis factor alpha monoclonal antibody therapy. Like inflammatory bowel disease, surgery is reserved for those who are resistant to medical therapy. A subset of patients have a poor disease course. Accurate methods to detect these patients and the optimal strategy for their treatment are not known at this time. © 2015 Baishideng Publishing Group Inc. All rights reserved.


Li A.W.,St Elizabeths Medical Center | Goldsmith C.-A.W.,Manchester College
Alternative Medicine Review | Year: 2012

Stress and anxiety have been implicated as contributors to many chronic diseases and to decreased quality of life, even with pharmacologic treatment. Efforts are underway to find non-pharmacologic therapies to relieve stress and anxiety, and yoga is one option for which results are promising. The focus of this review is on the results of human trials assessing the role of yoga in improving the signs and symptoms of stress and anxiety. Of 35 trials addressing the effects of yoga on anxiety and stress, 25 noted a significant decrease in stress and/or anxiety symptoms when a yoga regimen was implemented; however, many of the studies were also hindered by limitations, such as small study populations, lack of randomization, and lack of a control group. Fourteen of the 35 studies reported biochemical and physiological markers of stress and anxiety, but yielded inconsistent support of yoga for relief of stress and anxiety. Evaluation of the current primary literature is suggestive of benefits of yoga in relieving stress and anxiety, but further investigation into this relationship using large, well-defined populations, adequate controls, randomization and long duration should be explored before recommending yoga as a treatment option. Copyright © 2012 Alternative Medicine Review, LLC. All Rights Reserved.


Kraut J.A.,Veterans Health Administration Greater Los Angeles Heathcare System | Madias N.E.,St Elizabeths Medical Center
Nature Reviews Nephrology | Year: 2012

Acute metabolic acidosis is associated with increased morbidity and mortality because of its depressive effects on cardiovascular function, facilitation of cardiac arrhythmias, stimulation of inflammation, suppression of the immune response, and other adverse effects. Appropriate evaluation of acute metabolic acidosis includes assessment of acid-base parameters, including pH, partial pressure of CO 2 and HCO 3 ĝ̂' concentration in arterial blood in stable patients, and also in central venous blood in patients with impaired tissue perfusion. Calculation of the serum anion gap and the change from baseline enables the physician to detect organic acidoses, a common cause of severe metabolic acidosis, and aids therapeutic decisions. A fall in extracellular and intracellular pH can affect cellular function via different mechanisms and treatment should be directed at improving both parameters. In addition to supportive measures, treatment has included administration of base, primarily in the form of sodium bicarbonate. However, in clinical studies of lactic acidosis and ketoacidosis, bicarbonate administration has not reduced morbidity or mortality, or improved cellular function. Potential explanations for this failure include exacerbation of intracellular acidosis, reduction in ionized Ca 2+, and production of hyperosmolality. Administration of tris(hydroxymethyl)aminomethane (THAM) improves acidosis without producing intracellular acidosis and its value as a form of base is worth further investigation. Selective sodium-hydrogen exchanger 1 (NHE1) inhibitors have been shown to improve haemodynamics and reduce mortality in animal studies of acute lactic acidosis and should also be examined further. Given the important effects of acute metabolic acidosis on clinical outcomes, more intensive study of the pathogenesis of the associated cellular dysfunction and novel methods of treatment is indicated. © 2012 Macmillan Publishers Limited. All rights reserved.


Picel A.C.,University of California at San Diego | Kansal N.,St Elizabeths Medical Center
American Journal of Roentgenology | Year: 2014

OBJECTIVE. To understand the abdominal aortic aneurysm imaging characteristics that must be accurately described for endovascular aortic aneurysm repair treatment planning, including evaluation of the landing zones, aneurysm morphology, and vascular access.. CONCLUSION. A comprehensive understanding of preprocedural imaging is necessary to produce detailed and clinically useful imaging reports and assist the interventionalist in planning endovascular abdominal aortic aneurysm repair. © American Roentgen Ray Society.

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