Article Discussed on December 20, 2011

  • Traube E.  Embolic Risk in Atrial Fibrillation that Arises from Hyperthyroidism.  Tex Heart Inst J 2011.

Atrial fibrillation, the most common cardiac complication of hyperthyroidism, occurs in an estimated 10% to 25% of overtly hyperthyroid patients. The prevalence of atrial fibrillation increases with age in the general population and in thyrotoxic patients. Other risk factors for atrial fibrillation in thyrotoxic patients include male sex, ischemic or valvular heart disease, and congestive heart failure. The incidence of arterial embolism or stroke in thyrotoxic atrial fibrillation is less clear. There are many reports of arterial  thromboembolism associated with hyperthyroidism, including cases of young adults  without coexisting risk factors other than thyrotoxic atrial fibrillation. The use of anticoagulative agents to prevent thromboembolic sequelae of thyrotoxic atrial fibrillation is controversial: National organizations provide conflicting  recommendations in their practice guidelines. Herein, we review the medical literature and examine the evidence behind the recommendations in order to determine the best approach to thromboembolic prophylaxis in patients who have atrial fibrillation that is associated with hyperthyroidism.  PMID: 21720457  Fulltext

Article Discussed on December 19, 2011

  • Grey A. Vitamin D Repletion in Patients with Primary Hyperparathyroidism and Coexistent Vitamin D Deficiency. J Clin Endocrinol Metabol 2006.

Vitamin D insufficiency is common in patients with primary hyperparathyroidism (PHPT) and may be associated with more severe and progressive disease. Uncertainty exists, however, as to whether repletion of vitamin D should be undertaken in patients with PHPT. Here we report the effects of vitamin D repletion on biochemical outcomes over 1 yr in a group of 21 patients with mild PHPT [serum calcium <12 mg/dl (3 mmol/liter)] and coexistent vitamin D insufficiency [serum 25 hydroxyvitamin D [25(OH)D] <20 microg/liter (50 nmol/liter)]. In response to vitamin D repletion to a serum 25(OH)D level greater than 20 microg/liter (50 nmol/liter), mean levels of serum calcium and phosphate  did not change, and serum calcium did not exceed 12 mg/dl (3 mmol/liter) in any patient. Levels of intact PTH fell by 24% at 6 months (P < 0.01) and 26% at 12 months (P < 0.01). There was an inverse relationship between the change in serum  25(OH)D and that in intact PTH (r = -0.43, P = 0.056). At 12 months, total serum  alkaline phosphatase was significantly lower, and urine N-telopeptides tended to  be lower than baseline values (P = 0.02 and 0.13, respectively). In two patients, 24-h urinary calcium excretion rose to exceed 400 mg/d, but the group mean 24-h urinary calcium excretion did not change. These preliminary data suggest that vitamin D repletion in patients with PHPT does not exacerbate hypercalcemia and may decrease levels of PTH and bone turnover. Some patients with PHPT may experience an increase in urinary calcium excretion after vitamin D repletion.  PMID: 15644400 Fulltext

Articles Discussed on December 16, 2011

  • Gabardi S. A Review of Dietary Supplement-Induced Renal Dysfunction. Clin Am J Soc Nephrol 2007.

Complementary and alternative medicine (CAM) is a multibillion-dollar industry. Almost half of the American population uses some form of CAM, with many using them in addition to prescription medications. Most patients fail to inform their health care providers of their CAM use, and physicians rarely inquire. Annually, thousands of dietary supplement-induced adverse events are reported to Poison Control Centers nationwide. CAM manufacturers are not responsible for proving safety and efficacy, because the Food and Drug Administration does not regulate them. However, concern exists surrounding the safety of CAM. A literature search using MEDLINE and EMBASE was undertaken to explore the impact of CAM on renal function. English-language studies and case reports were selected for inclusion but were limited to those that consisted of human subjects, both adult and pediatric. This review provides details on dietary supplements that have been associated with renal dysfunction and focuses on 17 dietary supplements that have been associated with direct renal injury, CAM-induced immune-mediated nephrotoxicity, nephrolithiasis, rhabdomyolysis with acute renal injury, and hepatorenal syndrome. It is concluded that it is imperative that use of dietary supplements be monitored closely in all patients. Health care practitioners must take an active role in identifying patients who are using CAM and provide appropriate patient education. PMID: 17699493 . Fulltext


  • Spiller H.  Clinical experience with and analytical confirmation of “bath salts” and “legal highs” (synthetic cathinones) in the United States.  Clinical Toxicology 2011.

Recently, there has been a worldwide rise in the popularity and abuse of synthetic cathinones. In 2009 and 2010, a significant rise in the abuse of a new  group of synthetic cathinones was reported in Western Europe. In 2010, the rapid  emergence of a new drug of abuse, referred to as bath salts or “legal high,” occurred in the USA. The growing number of cases along with the alarming severity of the effects caused by the abuse of these substances prompted significant concern from both healthcare providers and legal authorities. We report the experience of the first 8 months of two regional poison centers after the emergence of a new group of substances of abuse.  METHOD: This was a retrospective  case series of patients reported to two poison centers with exposures to bath salts. Additionally, 15 “product samples” were obtained and analyzed for drug content using GC/MS.  RESULTS: There were 236 patients of which 184 (78%) were male. Age range was 16-64 years (mean 29 years, SD 9.4). All cases were intentional abuse. There were 37 separate “brand” names identified. Clinical effects were primarily neurological and cardiovascular and included: agitation (n = 194), combative behavior (n = 134), tachycardia (n = 132), hallucinations (n = 94), paranoia (n = 86), confusion (n = 83), chest pain (n = 40), myoclonus (n = 45), hypertension (n = 41), mydriasis (n = 31), CPK elevations (n = 22), hypokalemia (n = 10), and blurred vision (n = 7). Severe medical outcomes included death (n = 1), major (n  = 8), and moderate (n = 130). Therapies included benzodiazepines (n = 125),antipsychotics (n = 47), and propofol (n = 10). Primary dispositions of patients  were: 116 (49%) treated and released from ED, 50 (21%) admitted to critical care, 29 (12%) admitted to psych, and 28 (12%) lost to follow up. Nineteen patients had blood and/or urine analyzed using GC/MS. MDPV was detected in 13 of 17 live patients (range 24-241 ng/mL, mean 58 ng/mL). The four samples with no drug detected, reported last use of bath salts >20 h prior to presentation. Three of five patients had MDPV detected in urine (range 34-1386 ng/mL, mean 856 ng/mL). No mephedrone or methylone was detected in any sample. Quantitative analysis performed on postmortem samples detected MDPV in blood at 170 ng/mL and in urine  at 1400 ng/mL. No other synthetic cathinones were detected. DISCUSSION: This is the first report of MDPV exposures with quantitative blood level confirmation. Clinical effects displayed a sympathomimetic syndrome, including psychotic episodes often requiring sedation, movement disorders, and tachycardia. Within 8 months of their appearance, 16 states had added synthetic cathinones to the controlled substances list as a Schedule I drug.CONCLUSION: We report the emergence of a new group of substances of abuse in the  USA, known as bath salts, with quantitative results in 18 patients. State and federal authorities used timely information from poison centers on the bath salt  outbreak during investigations to help track the extent of use and the effects occurring from these new drugs. Close collaboration between state authorities and poison centers enhanced a rapid response, including legislation.  PMID: 21824061  Fulltext via library


  • Coppola M.  3,4-Methylenedioxypyrovalerone (MDPV):  Chemistry, pharmacology, and toxicology of a new designer drug of abuse marked online.  Toxicology Letters.

The illicit marketplace of substances of abuse continually offers for sale legal  alternatives to controlled drugs to a large public. In recent years, a new group  of designer drugs, the synthetic cathinones, has emerged as a new trend, particularly among young people. The 3,4-methylenedioxypyrovalerone (MDPV), one of this synthetic compounds, caused an international alert for its cardiovascular and neurological toxicity. This substance, sold as bath salts, has caused many serious intoxications and some deaths in several countries. The aim of this paper is summarise the clinical, pharmacological and toxicological information about this new designer drug.   PMID: 22008731  Fulltext via library

Liquid aspiration on pneumonia incidence

  • Ann Intern Med. 2008 Apr 1;148(7):509-18. Comparison of 2 interventions for liquid aspiration on pneumonia incidence: a randomized trial. Robbins J, Gensler G, Hind J, Logemann JA, Lindblad AS, Brandt D, Baum H, Lilienfeld D, Kosek S, Lundy D, Dikeman K, Kazandjian M, Gramigna GD, McGarvey-Toler S, Miller Gardner PJ.

BACKGROUND: Aspiration pneumonia is common among frail elderly persons with dysphagia. Although interventions to prevent aspiration are routinely used in these patients, little is known about the effectiveness of those interventions.

OBJECTIVE: To compare the effectiveness of chin-down posture and 2 consistencies (nectar or honey) of thickened liquids on the 3-month cumulative incidence of  pneumonia in patients with dementia or Parkinson disease.

DESIGN: Randomized, controlled, parallel-design trial in which patients were enrolled for 3-month periods from 9 June 1998 to 19 September 2005.

SETTING: 47 hospitals and 79 subacute care facilities.

PATIENTS: 515 patients age 50 years or older with dementia or Parkinson disease who aspirated thin liquids (demonstrated videofluoroscopically). Of these, 504 were followed until death or for 3 months.

INTERVENTION: Participants were randomly assigned to drink all liquids in a chin-down posture (n = 259) or to drink nectar-thick (n = 133) or honey-thick (n = 123) liquids in a head-neutral position.

MEASUREMENTS: The primary outcome was pneumonia diagnosed by chest radiography or by the presence of 3 respiratory indicators.

RESULTS: 52 participants had pneumonia, yielding an overall estimated 3-month cumulative incidence of 11%. The 3-month cumulative incidence of pneumonia was 0.098 and 0.116 in the chin-down posture and thickened-liquid groups, respectively (hazard ratio, 0.84 [95% CI, 0.49 to 1.45]; P = 0.53). The 3-month cumulative incidence of pneumonia was 0.084 in the nectar-thick liquid group compared with 0.150 in the honey-thick liquid group (hazard ratio, 0.50 [CI, 0.23 to 1.09]; P = 0.083). More patients assigned to thickened liquids than those assigned to the chin-down posture  intervention had dehydration (6% vs. 2%), urinary tract infection (6% vs. 3%), and fever (4% vs. 2%).

LIMITATIONS: A no-treatment control group was not included. Follow-up was limited to 3 months. Care providers were not blinded, and differences in cumulative pneumonia incidence between interventions had wide CIs.

CONCLUSION: No definitive conclusions about the superiority of any of the tested interventions can be made. The 3-month cumulative incidence of pneumonia was much lower than expected in this  frail elderly population. Future investigation of chin-down posture combined with nectar-thick liquid may be warranted to determine whether this combination better prevents pneumonia than either intervention independently. PMID: 18378947, Fulltext


  • Practical approach to the patient with hypereosinophilia. Roufosse F, Weller PF. J Allergy Clin Immunol. 2010 Jul;126(1):39-44. Epub 2010 Jun 9.

Markedly increased blood eosinophilia (ie, > or =1.5 x 10(9)/L), whether discovered fortuitously or found with signs and symptoms of associated organ involvement, commands diagnostic evaluation and often therapeutic interventions. This degree of hypereosinophilia is often but not uniformly associated with eosinophilic infiltration of tissues that can potentially lead to irreversible, life-threatening organ damage. Initial approaches focus on ascertaining that eosinophilia is not secondary to other underlying disease processes, including helminthic parasite infections, varied types of  adverse reactions to medications, and other eosinophil-associated syndromes, such as eosinophilic gastroenteritides, eosinophilic pneumonias, and Churg-Strauss syndrome vasculitis. If evaluations exclude eosinophilia attributable to secondary causes or other eosinophil-related syndromes or organ-specific diseases, attention must be directed to considerations of varied other forms of the hypereosinophilic syndromes, which include myeloproliferative variants, lymphocytic variants, and many of still unknown causes. Cognizant of the capacities of eosinophils to mediate tissue damage, the varied causes for  hypereosinophilia are considered, and a contemporary stepwise practical approach to the diagnosis and treatment of patients with hypereosinophilia is presented.  PMID: 20538328.  Free Fulltext

Article from Oct 20th

  • Arch Intern Med. 2001 Jan 8;161(1):25-34.  The diagnosis of glomerular diseases: acute glomerulonephritis and the nephroticsyndrome. Madaio MP, Harrington JT.

Rapid and efficient diagnosis of diseases presenting as acute glomerulonephritis and/or nephrotic syndrome is critical for early and appropriate therapy aimed at preservation of renal function. Although there may be overlap in clinical presentation, and some patients present with clinical features of both syndromes, this analysis serves as an initial framework to proceed with serologic testing and/or pathologic confirmation en route to final diagnosis. Efficient and timely diagnosis is essential in these situations because progression to end-stage renal disease may result if the underlying disease is not promptly treated. PMID: 11146695.   Fulltext via the Library

Comment in Arch Intern Med. 2001 Nov 26;161(21):2635  PMID: 11718628.    Fulltext via Library

Article discussed on Oct 18th

  • Ann Intern Med. 2011 Oct 4;155(7):I28. Epub 2011 Aug 28.  Colchicine treatment for recurrent pericarditis. [No authors listed. No abstract] PMID: 21873706  .  Fulltext via Library

Articles discussed on Oct 13th and 14th


  • JAMA. 2005 Oct 19;294(15):1944-56. Does this dyspneic patient in the emergency department have congestive heart failure? Wang CS, FitzGerald JM, Schulzer M, Mak E, Ayas NT.  Fulltext via the library.

CONTEXT: Dyspnea is a common complaint in the emergency department where physicians must accurately make a rapid diagnosis. OBJECTIVE: To assess the usefulness of history, symptoms, and signs along with  routine diagnostic studies (chest radiograph, electrocardiogram, and serum B-type natriuretic peptide [BNP]) that differentiate heart failure from other causes of dyspnea in the mergency department.  DATA SOURCES: We searched MEDLINE (1966-July 2005) and the reference lists from retrieved articles, previous reviews, and physical examination textbooks.
STUDY SELECTION: We retained 22 studies of various findings for diagnosing heart  failure in adult patients presenting with dyspnea to the emergency department.  DATA EXTRACTION: Two authors independently abstracted data (sensitivity, specificity, and likelihood ratios [LRs]) and assessed methodological quality.  DATA SYNTHESIS: Many features increased the probability of heart failure, with the best feature for each category being the presence of (1) past history of heart failure (positive LR = 5.8; 95% confidence interval [CI], 4.1-8.0); (2) the symptom of paroxysmal nocturnal dyspnea (positive LR = 2.6; 95% CI, 1.5-4.5); (3) the sign of the third heart sound (S(3)) gallop (positive LR = 11; 95% CI, 4.9-25.0); (4) the chest radiograph showing pulmonary venous congestion (positive  LR = 12.0; 95% CI, 6.8-21.0); and (5) electrocardiogram showing atrial fibrillation (positive LR = 3.8; 95% CI, 1.7-8.8). The features that best decreased the probability of heart failure were the absence of (1) past history of heart failure (negative LR = 0.45; 95% CI, 0.38-0.53); (2) the symptom of dyspnea on exertion (negative LR = 0.48; 95% CI, 0.35-0.67); (3) rales (negative LR = 0.51; 5% CI, 0.37-0.70); (4) the chest radiograph showing cardiomegaly (negative LR = 0.33; 95% CI, 0.23-0.48); and (5) any electrocardiogram abnormality (negative LR = 0.64; 95% CI, 0.47-0.88). A low erum BNP proved to be the most useful test (serum B-type natriuretic peptide <100 pg/mL; negative LR =  0.11; 95% CI, 0.07-0.16).  CONCLUSIONS: For dyspneic adult emergency department atients, a directed   history, physical examination, chest radiograph, and electrocardiography should be performed. If the suspicion of heart failure remains, obtaining a serum BNP level may be helpful, specially for excluding heart failure. PMID: 16234501

Papers from Sep 20th, 2011

• Rich JD, Shah SJ, Swamy RS, Kamp A, Rich S. Inaccuracy of Doppler echocardiographic estimates of pulmonary artery pressures in patients with pulmonary hypertension: implications for clinical practice. Chest. 2011 May;139(5):988-93. Epub 2010 Sep 23. PubMed PMID: 20864617. Comment in Chest. 2011 May;139(5):973-5. Chest. 2011 Jul;140(1):270; author reply 270-1.
BACKGROUND: Recent studies suggest that Doppler echocardiography (DE)-based estimates of pulmonary artery systolic pressure (PASP) may not be as accurate as previously believed. We sought to determine the accuracy of PASP measurements using DE compared with right-sided heart catheterization (RHC) in patients with pulmonary hypertension (PH). METHODS: We compared DE estimates of PASP to invasively measure PASP during RHC in 160 consecutive patients with PH (part one). To account for possible changes in hemodynamics between DE and RHC, we then prospectively determined PASP in an additional 23 consecutive patients undergoing simultaneous RHC and DE (part two). Bland-Altman analyses were performed to evaluate the agreement between RHC and DE measurements of PASP. Accuracy was predefined as 95% limits of agreement within ± 10 mm Hg for PASP estimates. RESULTS: In part one, there was moderate correlation between DE and RHC measurements of PASP (r = 0.68, P < .001). However, using Bland-Altman analysis, the bias for DE estimates of PASP was 2.2 mm Hg with 95% limits of agreement ranging from -34.2 to 38.6 mm Hg. DE estimates of PASP were determined to be inaccurate in 50.6% of patients. In part two, there was moderate correlation between DE and RHC measurements of PASP (r = 0.71, P < .01). However, despite simultaneous DE and RHC measurements, the bias for DE estimates of PASP was 8.0 mm Hg with 95% limits of agreement ranging from -28.4 to 44.4 mm Hg. CONCLUSIONS: DE estimates of PASP are inaccurate in patients with PH and should not be relied on to make the diagnosis of PH or to follow the efficacy of therapy. Fulltext: [Click the Article link associated with HighWire Press. You may have to login first with your last name and 6 digit employee ID (See MyCU under University of Colorado on the left side)].

• Odier C, Nguyen DK, Panisset M. Central pontine and extrapontine myelinolysis: from epileptic and other manifestations to cognitive prognosis. J Neurol. 2010 Jul;257(7):1176-80. Epub 2010 Feb 11. PubMed PMID: 20148334. 
The objective of this study is to review the presentation, outcome and aetiology of central pontine and extrapontine myelinolysis (CPEPM) in a tertiary hospital center. The study method is a case series and included identification of patients from University of Montreal Health Centre archives database (1995-2007). All diagnoses were confirmed by neuroimaging or brain autopsy. Twelve individuals (25-66 years old) presented heterogeneous manifestations. Co-morbidities included diabetes insipidus (n = 2), haemodialysis (n = 1), cirrhosis (n = 3), gastroenteritis (n = 2) and potomania (n = 1). Aetiologies included rapid correction of severe hyponatremia (n = 6)/acute hypernatremia (n = 1); immediate (n = 2) or remote (n = 1 with recurrent cirrhosis) orthotopic liver transplantation (OLT) with tacrolimus-induced immunosuppression (n = 3); and chronic alcoholism (n = 4, two with hyponatremia). Four individuals died acutely. Two were lost to follow-up. Six had good motor or cerebellar recovery. Neuropsychological evaluations (n = 5/6) revealed a subcortical/frontal dysfunction. Cognitive impairment represented the major remaining lasting sequel (n = 4). Three salient clinical syndromes were observed: (1) predominant cerebellar presentation in individuals with alcoholism (n = 4); (2) significant alteration of consciousness at presentation (n = 4), all resulting in death (OLT, n = 3); (3) seizures persisting after natremia correction (n = 2). Clinical presentation of CPEPM is heterogeneous and can even include seizures. Cognitive impairment should be screened as it is a significant factor limiting return to normal life.  Fulltext: [Click the Article link associated with SpringerLINK. You may have to login first with your last name and 6 digit employee ID (See MyCU under University of Colorado on the left side)].

• Martin RJ. Central pontine and extrapontine myelinolysis: the osmotic demyelination syndromes. J Neurol Neurosurg Psychiatry. 2004 Sep;75 Suppl 3:iii22-8. Review. PubMed PMID: 15316041; PubMed Central PMCID: PMC1765665. Fulltext:

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Papers discussed on Sept 8, 2011: Huntington’s Disease

Paulsen JS. Critical periods of suicide risk in Huntington’s disease. Am J Psychiatry. 2005 Apr;162(4):725-31. PMID: 15800145. (fulltext here: )

Roos RAC. Huntington’s disease: a clinical review. Orphanet Journal of Rare Diseases. 2010; 5:40. (fulltext here )