Loperamide cardiotoxicity: “A Brief Review”

Loperamide is a popular antidiarrheal medication that has been used for many years. It is currently gaining more attention among healthcare professionals due to its increasing potential for side effects. At present, it is considered safe enough to be sold over the counter. In contrast with other opioid agonists, loperamide is a peripherally acting μ‐receptor agonist exerting its effects mainly on the myenteric plexus of the gastrointestinal longitudinal muscle layer. It decreases peristalsis and fluid secretion resulting in longer gastrointestinal transit time. The bioavailability of the drug is extremely low. Moreover, it is actively excluded from the central nervous system; hence, it lacks the central effects of euphoria and analgesia at the recommended dosages. Loperamide abuse has been steadily increasing in the United States. Abusers typically ingest high doses in desire to achieve a satisfactory central nervous system drug penetration. This has made it a potential over the counter substitute for self‐treating opioid withdrawal symptoms and achieving euphoric effects.     

Cardiac resynchronization therapy: “Nonresponders” and “hyperresponders”

BACKGROUND: Cardiac resynchronization therapy (CRT) is a recognized treatment modality for patients with dilated cardiomyopathy (DCM), left bundle branch block, and severe cardiac failure. However, 30% of patients are "nonresponders." Intriguingly, the opposite case has not been reported until recently: Do some patients treated with CRT have a "complete" recovery and thus can be considered "hyperresponders"? OBJECTIVE: The purpose of this study was to investigate patients treated with CRT who have a "complete" functional recovery, with normalization of left ventricular function after therapy. METHODS: Eighty-four consecutive patients with DCM, sinus rhythm, and left bundle branch block in New York Heart Association functional class III and IV who were implanted with a CRT device were prospectively followed. Patients were considered to be "hyperresponders" if they concurrently fulfilled two criteria: functional recovery and left ventricular ejection fraction > or = 50%. RESULTS: Among the 84 patients with DCM, 11 (13%) were "hyperresponders" within 6 to 24 months after CRT (left ventricular ejection fraction increased from 25% +/- 8% to 60% +/- 6.5%, P = .001). Comparison of baseline parameters between "hyperresponders" and the remaining patients showed that only etiology of the DCM was statistically discriminative. All "hyperresponders" belonged to the group of patients with nonischemic DCM (18% vs 0%, P = .05). CONCLUSION: In a subset of patients successfully implanted with a CRT device, "complete" functional recovery associated with normalization of LV function was observed, giving rise to the concept of "hyperresponders." This finding is observed exclusively in the subgroup of patients with nonischemic DCM and suggests that left bundle branch block may be the causal factor of DCM in this subgroup of patients.     

The “art” of medicine and the “smokescreen” of the randomized trial off‐label use of vascular devices

Once a device is approved for sale in the United States by the Food and Drug Administration (FDA), it can legally be used by doctors to treat any condition a physician determines is medically appropriate. Based on postmarket published data and physician procedural experience, this may even become the standard of care when an alternative device either does not exist or is inferior in performance, even before FDA approval. This right of physicians to practice medicine without FDA approval is Federal law. The off‐label use of medical devices for the treatment of peripheral vascular disease has recently become the latest target by groups with interests that have little to do with patient care. This interference has begun to negatively impact the latitude necessary for physicians to best treat their patients. © 2008 Wiley‐Liss, Inc.     

A Comparison of How Generalists and Fellowship‐Trained Geriatricians Provide “Geriatric” Care

OBJECTIVES: To determine whether outpatient care provided to older patients by fellowship‐trained geriatricians is distinguishable from that provided by generalists. DESIGN: Observational study. SETTING: Three primary care clinics of an academic medical center. PARTICIPANTS: Random sample of 140 adults aged 65 and older receiving primary care at one of the clinics. MEASUREMENTS: A medical chart review involving records of 69 patients receiving primary care from a fellowship‐trained geriatrician and 71 patients receiving primary care from a generalist (general internal medicine or family practice) was conducted; information pertaining to two practice behaviors relevant to the care of older adults—avoidance of inappropriate prescribing and proactive assessments for geriatric syndromes—was abstracted. RESULTS: Geriatricians scored 17.6 out of a possible 24 points, on average; generalists scored 14.2 (P<.001). Geriatricians scored higher than generalists on prescribing and geriatric syndrome assessments. In a linear regression model adjusting for patient age and number of comorbidities and clustering according to provider, provider specialty was strongly associated with overall score (β coefficient for specialty=6.75, P<.001; 95% confidence interval=4.57–8.94). CONCLUSION: The practice style of fellowship‐trained geriatricians caring for older adults appears to differ from that of generalists with regard to prescribing behavior and assessment for geriatric syndromes.     

Percutaneous revascularization of the “unprotected” left main during acute myocardial infarction: “Dare to struggle! Dare to Win!”

Knowing the location of the vertebral and the internal mammary artery ostia is crucial during proximal subclavian artery percutaneous intervention to prevent inadvertent injury to either artery. We report a case of severe proximal left subclavian artery stenosis in a patient with a three‐vessel disease referred to coronary artery bypass graft surgery. Retrograde angiography via left radial access allowed visualization of the left internal mammary artery and the left vertebral artery ostia and placement of a Filterwire in the left vertebral artery. The proximal left subclavian artery was successfully stented without complications. Debris was retrieved in the Filterwire. © 2009 Wiley‐Liss, Inc.     

Melatonin prevents cell death and mitochondrial dysfunction via a SIRT1‐dependent mechanism during ischemic‐stroke in mice

Silent information regulator 1 (SIRT1), a type of histone deacetylase, is a highly effective therapeutic target for protection against ischemia reperfusion (IR) injury (IRI). Previous studies showed that melatonin preserves SIRT1 expression in neuronal cells of newborn rats after hypoxia–ischemia. However, the definite role of SIRT1 in the protective effect of melatonin against cerebral IRI in adult has not been explored. In this study, the brain of adult mice was subjected to IRI. Prior to this procedure, the mice were given intraperitoneal with or without the SIRT1 inhibitor, EX527. Melatonin conferred a cerebral‐protective effect, as shown by reduced infarct volume, lowered brain edema, and increased neurological scores. The melatonin‐induced upregulation of SIRT1 was also associated with an increase in the anti‐apoptotic factor, Bcl2, and a reduction in the pro‐apoptotic factor Bax. Moreover, melatonin resulted in a well‐preserved mitochondrial membrane potential, mitochondrial Complex I activity, and mitochondrial cytochrome c level while it reduced cytosolic cytochrome c level. However, the melatonin‐elevated mitochondrial function was reversed by EX527 treatment. In summary, our results demonstrate that melatonin treatment attenuates cerebral IRI by reducing IR‐induced mitochondrial dysfunction through the activation of SIRT1 signaling.     

Feasibility of Using Real Time “Live 3D” Echocardiography to Visualize the Stenotic Aortic Valve

Background: Aortic stenosis valve area (AS AVA) using the continuity equation (CE AVA) has limitations. Thus anatomic assessment of AS AVA would be useful. Method: AS AVA was measured using “live three‐dimensional (3D)” echocardiography that is a two‐dimensional (2D) display of a three‐dimensionally acquired 2–3 cm thick pyramidal image. In 52 aortic stenosis patients with CE AVA measurements, attempts were made at measuring AS AVA using 2D echocardiography (2D AVA) and real time, Live 3D echocardiography (3D AVA). 3D AVA and 2D AVA were compared to each other and to CE AVA. Results: 2D AVA could be obtained in 30 patients (58%) and 3D AVA in 50 patients (96%). Of the 30 patients in whom 3D AVA and 2D AVA were both measured, the correlation was 0.831 (P < 0.001). 3D AVA was smaller in 19 patients. In 17 of these patients, 3D AVA was closer to CE AVA. In two patients, 2D AVA was smaller than 3D AVA and in both patients 3D AVA was closer to CE AVA. The correlations between 2D AVA and CE AVA and 3D AVA and CE AVA were 0.581 and 0.673, respectively (all P < 0.001). Conclusion: A simplified 3D technique that is a “thick slice” 2D examination, can obtain AS AVA more often than a “thin slice” 2D echocardiogram. This 3D AVA correlates well with 2D AVA but is smaller and correlates better with CE AVA suggesting that the effective AS orifice is not planar but is more of a “tunnel” than a “flat ring.” (Echocardiography 2010;27:1011‐1020)     

“Cardio‐Neuromodulation” With a Multielectrode Irrigated Catheter: A Potential New Approach for Patients With Cardio‐Inhibitory Syncope

Syncope is frequently neurally mediated and can seriously affect quality of life. Different ablation strategies have been successfully performed. These approaches have not gained wide acceptance and are quite extensive and complex, exposing patients to significant risks. This article reports the case of a 16‐year‐old girl who was severely affected by frequent and prolonged episodes of syncope and was treated by tailored ablation of the anterior right ganglionated plexus with a multielectrode irrigated catheter. She had fainted >30 times in the 5 years preceding treatment, experiencing approximately 10 severe episodes of syncope in the previous 12 months. After 3 minutes of ablation, the P‐P interval was reduced by >400 milliseconds. Syncope disappeared and the patient has remained completely asymptomatic over a follow‐up of 22 months. The “reset” basal P‐P interval has remained unchanged (follow‐up electrocardiogram at 16 months). At 6 months, there was no residual heart rate activity <50 bpm. On 24‐hour rhythm registration, P‐P intervals ≥1,000 milliseconds (corresponding to a heart rate of ≤60 bpm) were reduced by >16,000 beats. We believe that this case report is original for several reasons: the unusual clinical presentation; the unique structure targeted; the very limited ablation, implying much lower risks for the patient; the anatomical approach; and the different endpoint. This new “cardio‐neuromodulation” approach could be useful for the treatment of patients with neurally mediated syncope.