23rd annual selected topics in internal medicine conference


John Bundrick, M.D. of the Department of General Internal Medicine discusses his presentation General Internal Medicine: Physical Exam Pearls, part of Mayo Clinic’s 23rd annual Selected Topics in Internal Medicine conference, January 24 – 28, 2011 in Koloa, Kauai, Hawaii.

COURSE DESCRIPTION
This postgraduate course designed to update general internists, internist-subspecialists, family medicine specialists, and other primary health care providers on selected internal medicine topics.  Expert faculty provide lectures that are clinically focused and relevant to the generalist practice.

COURSE LEARNING OBJECTIVES

• Summarize the management of pulmonary nodules based on radiographic features
• Summarize recent updates, clinical studies, and new guidelines that impact practice in general medicine
• Describe prevention and management strategies for kidney stones
• Choose appropriate duration of anticoagulation for patients with DVT
• Summarize the management for common dermatologic problems
• Review cases in women’s health
• Learn common clinical pearls in the areas of general internal medicine, gastroenterology, and infectious diseases
• Summarize new practice developments in oncology, Parkinson’s Disease, and complimentary medicine
• Describe common problems encountered in post-gastric bypass patients
• Review cases in crystalline arthropathy

Read more about the conference or register.

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By Miriam Wuensch | Posted in General Medical | Tagged , , , , , | Leave a comment

Mitochondrial dysfunction and susceptibility to atrial fibrillation in the Elderly


Dr. Arshad Jahangir of the Division of Cardiovascular Diseases at Mayo Clinic Arizona studies aging and its effect on the heart’s response to stress. Dr. Jahangir and co-investigators were recently awarded  a 4-year grant from the National Heart, Lung and Blood Institute of the National Institutes of Health to study mechanistic insights into the role of cardiac mitochondria in defining the substrate for atrial fibrillation (AF), the most common arrhythmia encountered in clinical practice.

Summary:
With a projected 6-fold increase in the prevalence and a cost exceeding $15 billion per year, AF remains a major national health problem. Despite the recognition that aging increases susceptibility of the atria to fibrillation, with a 100-fold higher prevalence in the older-elderly compared to young adults, the molecular basis for this susceptibility remains unknown.

Changes in hemodynamic, vascular, and metabolic factors that accompany aging or associated disease contribute to functional and structural atrial remodeling, promoting cardiomyocytes loss and fibrosis that increases susceptibility to fibrillation. The molecular bases for such alterations contributing to the progression of atrial dysfunction, however, are not well defined.

In preliminary studies using human atrial tissue, a distinct transcriptional downregulation of genes regulating mitochondrial energetics and signaling pathways involved in energy production and utilization, cell loss and fibrosis was demonstrated with aging and AF.

Additionally, functional defects with impaired capacity to maintain cellular energetics and ionic homeostasis under stress were demonstrated in senescent mitochondria. The defects can be ameliorated by modulating mitochondrial membrane permeability.

Based on these findings, Dr. Jahangir and his co-investigators hypothesize that susceptibility to AF in the elderly results from diminished mitochondrial functional reserves in the atria. The diminished reserves promote cardiomyocyte loss and fibrosis due to enhanced sensitivity of the myocardium to energetic failure, calcium overload and oxidative injury during stress, facilitating development and progression of the substrate for AF.

The study proposes:

  1. to identify differences in atrial structure and function, energetics and mitochondrial susceptibility to stress in patients with low or high risk for the development of AF and those with paroxysmal, persistent or permanent AF
  2. to identify mechanisms underlying atrial energetic deficits and mitochondrial dysfunction predisposing to enhanced cell loss and fibrosis
  3. to determine the protective role of mitochondrial modulation against mitochondrial and cellular injury during metabolic stress in patients at risk for or with AF

These aims will be achieved using atrial tissue obtained from patients undergoing coronary artery bypass surgery without or with risk factors for AF (heart failure, hypertension, or mitral regurgitation) or a history of paroxysmal, persistent or permanent AF. To assess those at risk of AF, those who develop AF following surgery and those with AF, investigators will use an  integrative approach that combines:

  • clinical information
  • in vivo and in vitro atrial structural and functional data obtained by imaging
  • comprehensive cellular and mitochondrial studies assessing differences in ultrastructural, functional, molecular, genetic and proteomic changes in atrial tissue

The results will provide new insights into the role of mitochondria priming the substrate for AF and identify novel targets for the development of therapeutics toward prevention of AF.

Co-investigators:
Francisco A. Arabia, M.D., Louis A. Lanza, M.D., Marek Belohlavek, M.D., Ph.D.

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By Miriam Wuensch | Posted in Cardiovascular | Tagged , , , , | Comments (3)

Research improves treatment for patients with statin-associated adverse effects


Dr. Stephen Kopecky of the Department of Cardiovascular Diseases at Mayo Clinic describes statin intolerance as a condition that can be hard to diagnose and for which more research is needed.

Statins are the most commonly used drugs in the world for the treatment of high cholesterol. Classic patient reactions to statins, however, include muscle aches, cramps and weakness. Reactions may occur within a few months or up to several years later.

To better care for these patients, Mayo Clinic established the Statin Intolerance Clinic to diagnose, risk stratify, and treat patients with statin-associated adverse effects. Related research focuses on drugs that may help patients who gave up on statins years ago and on genetic testing that will allow physicians to predict the drugs and dosages that may be most effective for each patient.

Learn more about the Mayo Clinic Statin Intolerance Clinic and Dr. Kopecky’s research.

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By Miriam Wuensch | Posted in Cardiovascular | Tagged , , , , | Comments (1)

Carotid ultrasound identifies high-risk subclinical atherosclerosis in adults with low Framingham risk scores


Dr. Robert (Todd) Hurst discusses research conducted at Mayo Clinic in Arizona that suggests that measuring the amount of artery disease an individual has may allow physicians to make more informed recommendations to patients.

Researchers  investigated whether the Carotid Intima Media Thickness (CIMT) test, a simple, safe ultrasound test to measure artery disease in the main artery in the neck, would help them better identify individuals that may be at risk. The study was published in the August 2010 issue of the  Journal of American Society of Echocardiography.

ABSTRACT
Background
Worldwide, cardiovascular (CV) disease remains the most common cause of morbidity and mortality. Although effective in predicting CV risk in select populations, the Framingham risk score (FRS) fails to identify many young individuals who experience premature CV events. Accordingly, the aim of this study was to determine the prevalence of high-risk carotid intima-media thickness (CIMT) or plaque, a marker of atherosclerosis and predictor of CV events, in young asymptomatic individuals with low and intermediate FRS (<2% annualized event rate) using the carotid ultrasound protocol recommended by the American Society of Echocardiography and the Society of Vascular Medicine.

Methods
Individuals aged < or = 65 years not taking statins and without diabetes mellitus or histories of coronary artery disease underwent CIMT and plaque examination for primary prevention. Clinical variables including lipid values, family history of premature coronary artery disease, and FRS and subsequent pharmacotherapy recommendations were retrospectively collected for statistical analysis.

Results
Of 441 subjects (mean age, 49.7 + or – 7.9 years), 184 (42%; 95% confidence interval, 37.3%-46.5%) had high-risk carotid ultrasound findings (CIMT > or = 75th percentile adjusted for age, gender, and race or presence of plaque). Of those with the lowest FRS of < or =5% (n = 336) (mean age, 48.0 + or – 7.6 years; mean FRS, 2.5 + or – 1.5%), 127 (38%; 95% confidence interval, 32.6%-43.0%) had high-risk carotid ultrasound findings. For individuals with FRS < or = 5% and high-risk carotid ultrasound findings (n = 127; mean age, 47.3 + or – 8.1 years; mean FRS, 2.5 + or – 1.5%), lipid-lowering therapy was recommended by their treating physicians in 77 (61%).

Conclusions
Thirty-eight percent of asymptomatic young to middle-aged individuals with FRS < or = 5% have abnormal carotid ultrasound findings associated with increased risk for CV events. Pharmacologic therapy for CV prevention was recommended in the majority of these individuals. The lack of radiation exposure, relatively low cost, and ability to detect early-stage atherosclerosis suggest that carotid ultrasound for CIMT and plaque detection should continue to be explored as a primary tool for CV risk stratification in young to middle-aged adults with low FRS.

Authors
Mackram Eleid, M.D.; Steven Lester, M.D.; Troy Wiedenbeck, M.D.; Sharad Patel, M.D.; Christopher Appleton, M.D.; Matthew Nelson, M.D.; J. Humphries; Robert Hurst, M.D.

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By Miriam Wuensch | Posted in Cardiovascular | Tagged , , , , , , , , | Comments (1)

Association of Aβ42, Aβ40 and Aβ42/Aβ40 with cognitive impairment not demented (CIND) and dementia in persons of Mexican ancestry (SALSA study): Different for diabetics versus non-diabetics?


Dr. Neill Graff-Radford of the Department of Neurology at Mayo Clinic in Florida discusses a recent study that used potential biomarkers predicting cognitive impairment to study persons of Mexican ancestry, in whom the incidence of type 2 diabetes is high. Researchers found that a low Aβ42/Aβ40 ratio or low Aβ42 may indicate impending dementia in non-diabetic study group participants, but that finding did not hold true for the group as a whole.

 

ABSTRACT
Background
Plasma Aβ40 and Aβ42 are potential biomarkers predicting cognitive impairment and dementia. These biomarkers have not been studied in persons of Mexican ancestry in whom type 2 diabetes is high. We evaluated the association of plasma Aβ40 and Aβ42 levels as well as their ratio with risk of CIND and Dementia.

Methods
In a nested case-control study, we matched normal controls (n=403) to incident dementia/CIND cases (n=211) by age at diagnosis (+/- 2 years). We used those with a plasma sample before or at dementia/CIND diagnosis. Using sandwich ELISAs, we measured Aβ40 with antibodies BNT77/BA27 and Aβ42 using BNT77/BC-05. Il-6, LDL-C, insulin and glucose were obtained from fasting samples at diagnosis. Diabetes was defined using ADA standards. Diabetes was present in 42% of cases and 26% of controls (p<0.0001). Insulin sensitivity was calculated using the QUICKI formula. Conditional logistic regression models including age as a classification variable APOE4 and time between sample and diagnosis (model 1) were used to assess association of each Aβ measure (after log transformation) with risk of dementia/CIND. We explored interactions with diabetic status. Model 2 adjusted for diabetic status, insulin sensitivity, LDL and Il-6.

Results
One standard deviation (SD) increase in log Aβ40 was associated with increased risk of dementia/CIND (OR=1.69, 95% confidence interval: 1.07-2.67, model 1). Adjustment for additional covariates reduced the association (OR=1.22, 0.75 – 2.05, model 2). Neither Aβ42 nor the Aβ42/Aβ40 ratio was associated with dementia/CIND. Tests for interaction of Aβ42 and Aβ42/Aβ40 with diabetes at dementia/CIND diagnosis were significant, however, for both model 1 and model 2. Among non-diabetics, a one SD increase in log Aβ42 was associated with a lower risk of dementia/CIND (OR=0.79, 0. 61-1.01, p for interaction=0.02, model 2). Also among non-diabetics, a one SD increase in Aβ42/Aβ40 (log transformed) was associated with a lower risk (OR=0.75, 0.59-0.96, p for interaction=0.02, model 2) of dementia/CIND.

Conclusion
In non-diabetic persons of Mexican ancestry, as in many Caucasians studies, a low Aβ42/Aβ40 ratio or low Aβ42 may indicate impending dementia. This outcome was not found for the whole group including diabetics. These results may help explain some of the contradictory findings in the literature. Further studies are needed in diabetics.

Learn more about Dr. Graff-Radford’s research.

Authors
Neill Graff-Radford, M.D.; Julia Crook, Ph.D.; John Lucas, Ph.D.; Linda Younkin; Greg Nah; Steven Younkin, M.D., Ph.D., senior author; Mary Haan, senior author

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By Miriam Wuensch | Posted in Neurology | Tagged , , , , , | Leave a comment

Radical prostatectomy performed without incision


Dr. Mitchell Humphreys discusses a new surgical procedure that uses natural orifices as access points for cancer treatment. Natural Orifice Transluminal Endoscopic Surgery (NOTES) was recently used to perform a radical prostatectomy at Mayo Clinic in Arizona. The patient’s prostate and cancer were successfully removed through his urethra.

ABSTRACT
Natural orifice translumenal endoscopic surgical radical prostatectomy: proof of concept

This abstract reflects preliminary work completed on cadavers.  It is not reflective the of actual surgery. The study was published in the April 2009 issue of the Journal of Endourology.

Background: Innovations in minimally invasive surgery have led to the proposal of incision-free natural orifice translumenal endoscopic surgery (NOTES). This manuscript describes the initial technique of natural orifice translumenal endoscopic surgical radical prostatectomy (NOTES-RP).

Methods: NOTES-RP was performed on four male cadavers in a surgical simulation laboratory setting. The 100 W holmium:yttrium-aluminum-garnet laser, 550 microm end-firing laser fiber, 26F resectoscope, 7F laser stabilizing catheter, and continuous irrigation were used to radically resect and deliver the prostate of each cadaver into the bladder. The neurovascular bundles were preserved bilaterally, as well as the dorsal venous complex, bladder neck, and external sphincter. The entire resection was performed with the laser, while a rigid offset 27F nephroscope was used to perform the vesicourethral anastomosis using a laparoscopic suture device and knot pusher in an interrupted fashion. The prostate tissue was removed endoscopically with a tissue morcellator. After the initial NOTES-RP, a pelvic exploration with biopsy of neurovascular bundles, bladder, and urethral margins was performed.

Results: NOTES-RP was successfully executed in the cadaveric model. Pathologic evaluation of tissue demonstrates complete removal of all prostate tissue with preservation of the neurovascular bundles bilaterally as well as the external urinary sphincter.

Conclusion: The present work demonstrates the feasibility of NOTES-RP in the cadaver model. While further testing and instrument modification are necessary before clinical application, this concept demonstrates the evolving nature of minimally invasive surgery and what could be possible for patients.

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By Miriam Wuensch | Posted in Cancer, Urology | Tagged , , , , , | Comments (1)

Coronary artery disease management update


Charanjit Rihal, M.D., chair of the Mayo Clinic Division of Cardiovascular Diseases, discusses advancements in the early detection and treatment of coronary artery disease, including medical therapy and revascularization in the form of percutaneous coronary intervention and bypass surgery. Dr. Rihal also discusses a continuing medical education course, Coronary Artery Disease: Prevention, Detection and Treatment, offered October 22-24, 2010, in Las Vegas.

Learn more about Dr. Rihal’s recent research activities.

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By Miriam Wuensch | Posted in Cardiovascular | Tagged , , , , | Leave a comment

Identification and treatment of eating disorders in the primary care setting


Dr. Leslie Sim discusses a clinical review that surveys recent literature related to the main eating disorders seen in primary care, including anorexia nervosa (AN), bulimia nervosa (BN), binge-eating disorder (BED), night-eating syndrome (NES), and eating disorder not otherwise specified (EDNOS). The review, published in the August 2010 issue of Mayo Clinic Proceedings, details the signs and symptoms of each of these eating disorders, screening tests to detect them, and pharmacological and psychosocial approaches to their treatment.

ABSTRACT
Background:
Eating disorders, which are associated with a host of adverse medical morbidities, negative psychological sequelae, and considerable reductions in quality of life, should be diagnosed and treated promptly. However, primary care physicians may find it uniquely challenging to detect eating disorders in their early stages, before obvious physical problems arise and while psychological symptoms are subtle. Although psychological symptoms may dominate the presentation, the physician is an integral member of the treatment team and is in a unique role to diagnose and treat eating disorders.

Methods: This clinical review surveys the eating disorders literature, identified by searching MEDLINE and PubMed for articles published from January 1, 1983, to September 30, 2009, using the following keywords: anorexia nervosa, bulimia nervosa, eating disorders, eating disorders NOS, binge eating, binge eating disorder, and night eating syndrome. This review also focuses on practical issues faced by primary care physicians in the management of these conditions and other issues central to the care of these complex patients with medical and psychiatric comorbid conditions.

Conclusions: Eating disorders are severe psychological illnesses associated with a host of adverse medical morbidities, negative psychological sequelae, and substantial reductions in quality of life. Given these consequences and the fact that health service utilization among people with eating disorders is relatively high, it is particularly important for physicians to adequately assess for these disorders. Although the eating disorders presented in this review vary widely in their demographic, weight, and symptom presentations, most benefit from a coordinated multidisciplinary effort, often involving specialized psychological treatment, medication management, and medical monitoring.

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By Carol Lammers | Posted in Pediatric, Psychiatry | Tagged , , , , | Comments (1)

REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century


A study of 27 patients with histories of REM sleep behavioral disorder predating onset of clinical Parkinson’s disease (PD), dementia with Lewy bodies (DLB), or multiple system atrophy (MSA) by more than 15 years illustrates that the ά-synuclein pathogenic process may start decades before the first symptoms of PD, DLB, or MSA. This study was published on July 28, 2010 in Neurology.

ABSTRACT
Background: Idiopathic REM sleep behavior disorder (RBD) may be the initial manifestation of synucleinopathies (Parkinson disease [PD], multiple system atrophy [MSA], or dementia with Lewy bodies [DLB]).

Methods: We used the Mayo medical records linkage system to identify cases presenting from 2002 to 2006 meeting the criteria of idiopathic RBD at onset, plus at least 15 years between RBD and development of other neurodegenerative symptoms. All patients underwent evaluations by specialists in sleep medicine to confirm RBD, and behavioral neurology or movement disorders to confirm the subsequent neurodegenerative syndrome.

Results: Clinical criteria were met by 27 patients who experienced isolated RBD for at least 15 years before evolving into PD, PD dementia (PDD), DLB, or MSA. The interval between RBD and subsequent neurologic syndrome ranged up to 50 years, with the median interval 25 years. At initial presentation, primary motor symptoms occurred in 13 patients: 9 with PD, 3 with PD and mild cognitive impairment (MCI), and 1 with PDD. Primary cognitive symptoms occurred in 13 patients: 10 with probable DLB and 3 with MCI. One patient presented with primary autonomic symptoms, diagnosed as MSA. At most recent follow-up, 63% of patients progressed to develop dementia (PDD or DLB). Concomitant autonomic dysfunction was confirmed in 74% of all patients.

Conclusions: These cases illustrate that the ά-synuclein pathogenic process may start decades before the first symptoms of PD, DLB, or MSA. A long-duration preclinical phase has important implications for epidemiologic studies and future interventions designed to slow or halt the neurodegenerative process.

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By Carol Lammers | Posted in Neurology | Tagged , , | Leave a comment

Stability of the diagnosis of mild cognitive impairment


Amnestic mild cognitive impairment (aMCI) is a subtype of MCI that has been associated with a likely progression to Alzheimer’s disease (AD). However, some subjects with MCI revert to “normal cognition,” and this raises the question of the stability of the diagnosis. A recent Mayo Clinic Study found that while the diagnosis of MCI was occasionally given to persons who subsequently were considered cognitively normal, such outcomes were uncommon.

Dr. Ronald Petersen presented these finding at the 2010 ICAD annual meeting.

ABSTRACT
Background: Amnestic mild cognitive impairment  is a subtype of MCI that has been associated with a likely progression to Alzheimer’s disease, and non-amnestic MCI (naMCI) likely represents the early stages of AD and non-AD dementias. However, some subjects with MCI revert to “normal cognition,” and this raises the question of the stability of the diagnosis.

Methods: The Mayo Clinic Study of Aging is a longitudinal population-based study of non-demented subjects ages 70-89 years. The subjects are evaluated every 15 months with a history from the subject and informant, neuropsychological tests covering four cognitive domains and a neurologic evaluation performed by a physician. A consensus conference is convened after each subject is evaluated, and the diagnosis of normal, aMCI, naMCI and dementia are made according to published criteria. A consensus diagnosis is obtained when two of the three evaluators agree with the diagnosis, and concordance is achieved when all three evaluators agree.

Results: For this study, 329 subjects with MCI at baseline were evaluated 15 and 30 months later. The overall incidence rate of developing dementia from MCI was 6.4% per year. For aMCI, the rate was 6.9%, and 5.2% for naMCI. In general, multi-domain aMCI had the highest rate of progression at 11.1% per year, according to consensus diagnoses. Using the concordant diagnoses, the overall rate of progression was 7.1% per year and 7.8% per year for aMCI and 5.5% per year for naMCI. The highest incidence rates were achieved for concordant diagnoses of multi-domain aMCI at 12.3% per year. The rates of reversion to normal for consensus MCI diagnoses was 8.8% per year, and for concordant diagnoses, 6.8% per year. The likelihood of remaining stable or progressing to dementia over three years of followup was quite high, 91.2% for consensus and 93.2% for concordant MCI diagnoses.

Conclusion: While the diagnosis of was MCI occasionally given to persons who subsequently were considered cognitively normal, such outcomes were uncommon. A diagnosis of MCI implies genuine cognitive impairment and represents a stable or progressive condition. Support for this study came from NIA: U01 AG006786 and P50 AG016574.

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By Carol Lammers | Posted in Neurology | Tagged , , , , | Comments (1)