Showing papers by "Ochsner Medical Center published in 2010"

Sacral Nerve Stimulation for Fecal Incontinence: Results of a 120-Patient Prospective Multicenter Study

Abstract: Background:Sacral nerve stimulation has been approved for use in treating urinary incontinence in the United States since 1997, and in Europe for both urinary and fecal incontinence (FI) since 1994. The purpose of this study was to determine the safety and efficacy of sacral nerve stimulation in a l

Switching to once-daily liraglutide from twice-daily exenatide further improves glycemic control in patients with type 2 diabetes using oral agents.

Abstract: OBJECTIVE To evaluate efficacy and safety of switching from twice-daily exenatide to once-daily liraglutide or of 40 weeks of continuous liraglutide therapy. RESEARCH DESIGN AND METHODS When added to oral antidiabetes drugs in a 26-week randomized trial (Liraglutide Effect and Action in Diabetes [LEAD]-6), liraglutide more effectively improved A1C, fasting plasma glucose, and the homeostasis model of β-cell function (HOMA-B) than exenatide, with less persistent nausea and hypoglycemia. In this 14-week extension of LEAD-6, patients switched from 10 μg twice-daily exenatide to 1.8 mg once-daily liraglutide or continued liraglutide. RESULTS Switching from exenatide to liraglutide further and significantly reduced A1C (0.32%), fasting plasma glucose (0.9 mmol/l), body weight (0.9 kg), and systolic blood pressure (3.8 mmHg) with minimal minor hypoglycemia (1.30 episodes/patient-year) or nausea (3.2%). Among patients continuing liraglutide, further significant decreases in body weight (0.4 kg) and systolic blood pressure (2.2 mmHg) occurred with 0.74 episodes/patient-year of minor hypoglycemia and 1.5% experiencing nausea. CONCLUSIONS Conversion from exenatide to liraglutide is well tolerated and provides additional glycemic control and cardiometabolic benefits.

Cardiopulmonary exercise testing in patients with pulmonary arterial hypertension: An evidence-based review

Abstract: Background There is an increasing recognition of the potential value of cardiopulmonary exercise testing (CPX) in patients with pulmonary hypertension (PH). Key CPX characteristics in these patients include: (1) a diminished aerobic capacity; (2) an abnormally elevated minute ventilation–carbon dioxide production relationship; and (3) an abnormally diminished partial pressure of end-tidal carbon dioxide. Given the burgeoning number of original research investigations utilizing CPX in patients with PH, a summation of the presently available body of literature seems timely. Methods A literature search was conducted in pubmed using “cardiopulmonary exercise testing” and “pulmonary arterial hypertension” as key phrases. Only studies conducting exercise testing with simultaneous ventilatory expired gas analysis in subjects with a confirmed diagnosis of pulmonary arterial hypertension were included. Twenty-three investigations were included in this review. Nineteen of the investigations assessed cohorts with resting pulmonary arterial hypertension as the sole diagnosis. Two investigations assessed subjects with chronic obstructive pulmonary disease and pulmonary arterial hypertension: one assessed subjects with pulmonary fibrosis and pulmonary arterial hypertension, and another included groups with exercise-induced pulmonary arterial hypertension and resting pulmonary arterial hypertension. Results Collectively, these investigations indicate variables obtained from CPX: (1) reflect varying degrees of PH severity; (2) positively respond to several pharmacologic and surgical interventions; and (3) may provide prognostic value. Conclusions Currently, CPX is not widely utilized in patients with PH. Although more research is required in a number of areas, the present evidence-based review indicates this exercise testing technique may provide valuable information in the PH population.

Cardiopulmonary exercise testing: relevant but underused.

Abstract: Cardiopulmonary exercise testing (CPX) is a relatively old technology, but has sustained relevance for many primary care clinical scenarios in which it is, ironically, rarely considered. Advancing computer technology has made CPX easier to administer and interpret at a time when our aging population is more prone to comorbidities and higher prevalence of nonspecific symptoms of exercise intolerance and dyspnea, for which CPX is particularly useful diagnostically and prognostically. These discrepancies in application are compounded by patterns in which CPX is often administered and interpreted by cardiology, pulmonary, or exercise specialists who limit their assessments to the priorities of their own discipline, thereby missing opportunities to distinguish symptom origins. When used properly, CPX enables the physician to assess fitness and uncover cardiopulmonary issues at earlier phases of work-up, which would therefore be especially useful for primary care physicians. In this article, we provide an overview of CPX principles and testing logistics, as well as some of the clinical contexts in which it can enhance patient care.

Body composition and heart failure prevalence and prognosis: getting to the fat of the matter in the "obesity paradox".

Abstract: Obesity has been increasing in epidemic proportions in both adults and children in the United States.1,2 Overweightness and obesity are now critical problems, with the prevalence among adults increasing by nearly 50% during the past 2 decades3; currently nearly 70% of adults are classified as being either overweight or obese compared with fewer than 25% 40 years ago.2,3 Moreover, the distribution of body mass index (BMI) in the United States has drastically shifted in a skewed fashion toward higher values, such that the proportion of the population meeting criteria for morbid obesity has increased more markedly than for overweight and mild levels of obesity.1-4 If we fail to stop this ongoing obesity epidemic, we may soon witness an abrupt end to, or even worse a reversal of, the steady increase in life expectancy noted during the past century.2,5

Cystatin E/M suppresses legumain activity and invasion of human melanoma

Abstract: Background: High activity of cysteine proteases such as legumain and the cathepsins have been shown to facilitate growth and invasion of a variety of tumor types. In breast cancer, several recent studies have indicated that loss of the cysteine protease inhibitor cystatin E/M leads to increased growth and metastasis. Although cystatin E/M is normally expressed in the skin, its role in cysteine protease regulation and progression of malignant melanoma has not been studied. Methods: A panel of various non-melanoma and melanoma cell lines was used. Cystatin E/M and C were analyzed in cell media by immunoblotting and ELISA. Legumain, cathepsin B and L were analyzed in cell lysates by immunoblotting and their enzymatic activities were analyzed by peptide substrates. Two melanoma cell lines lacking detectable secretion of cystatin E/M were transfected with a cystatin E/M expression plasmid (pCST6), and migration and invasiveness were studied by a Matrigel invasion assay. Results: Cystatin E/M was undetectable in media from all established melanoma cell lines examined, whereas strong immunobands were detected in two of five primary melanoma lines and in two of six lines derived from patients with metastatic disease. Among the four melanoma lines secreting cystatin E/M, the glycosylated form (17 kD) was predominant compared to the non-glycosylated form (14 kD). Legumain, cathepsin B and L were expressed and active in most of the cell lines, although at low levels in the melanomas expressing cystatin E/M. In the melanoma lines where cystatin E/M was secreted, cystatin C was generally absent or expressed at a very low level. When melanoma cells lacking secretion of cystatin E/M were transfected with pCST6, their intracellular legumain activity was significantly inhibited. In contrast, cathepsin B activity was not affected. Furthermore, invasion was suppressed in cystatin E/M over-expressing melanoma cell lines as measured by the transwell Matrigel assay. Conclusions: These results suggest that the level of cystatin E/M regulates legumain activity and hence the invasive potential of human melanoma cells.

Identifying Patients at High Risk of a Cardiovascular Event in the Near Future: Current Status and Future Directions: Report of a National Heart, Lung, and Blood Institute Working Group

Abstract: The National Heart, Lung, and Blood Institute convened a working group to provide basic and clinical research recommendations to the National Heart, Lung, and Blood Institute on the development of an integrated approach for identifying those individuals who are at high risk for a cardiovascular event such as acute coronary syndromes (ACS) or sudden cardiac death in the “near term” The working group members defined near-term as occurring within 1 year of the time of assessment The participants reviewed current clinical cardiology practices for risk assessment and state-of-the-science techniques in several areas, including biomarkers, proteomics, genetics, psychosocial factors, imaging, coagulation, and vascular and myocardial susceptibility This report presents highlights of these reviews and a summary of suggested research directions ### Near-Term Risk The proper deployment of preventive strategies requires an accurate classification system that allows the physician to target intensive treatments to the highest-risk patients A commonly recommended approach is a multivariable assessment such as the Framingham Risk Score (FRS)1 Although the FRS is recommended in many guidelines on cardiovascular risk assessment,2 it has some limitations It does not include several factors of the metabolic syndrome (glucose intolerance, central obesity, and hypertriglyceridemia), nor does it include family history Moreover, the FRS classifies risk over a period of 10 years rather than in the near term (within 1 year) Indeed, no algorithm has been developed that accurately predicts near-term risk across diverse populations The ability to forecast near-term risk of ACS or sudden cardiac death would represent an important advance in cardiovascular medicine because it would clarify which individuals are in most urgent need of intervention It would help identify those rare asymptomatic, apparently healthy individuals who are in imminent danger of a cardiovascular event yet ordinarily would not receive therapy at all In asymptomatic individuals judged to be at intermediate or …

Unrecognized Pretransplant and Donor-Derived Cryptococcal Disease in Organ Transplant Recipients

Abstract: Background: Cryptococcosis occurring ≤30 days after transplantation is an unusual event, and its characteristics are not known. Methods: Patients included 175 solid-organ transplant (SOT) recipients with cryptococcosis in a multicenter cohort. Very early-onset and late-onset cryptococcosis were define as disease occurring ≤30 days or >30 days after transplantation, respectively. Results: Very early-onset disease developed in 9 (5%) of the 175 patients at a mean of 5.7 days after transplantation. Overall, 55.6% (5 of 9) of the patients with very early-onset disease versus 25.9% (43 of 166) of the patients with late-onset disease were liver transplant recipients (P = .05). Very early cases were more likely to present with disease at unusual locations, including transplanted allograft and surgical fossa/site infections (55.6% vs 7.2%; P < .001). Two very early cases with onset on day 1 after transplantation (in a liver transplant recipient with Cryptococcusisolated from the lung and a heart transplant recipient with fungemia) likely were the result of undetected pretransplant disease. An additional 5 cases involving the allograft or surgical sites were likely the result of donor-acquired infection. Conclusions: A subset of SOT recipients with cryptococcosis present very early after transplantation with disease that appears to occur preferentially in liver transplant recipients and involves unusual sites, such as the transplanted organ or the surgical site. These patients may have unrecognized pretransplant or donor-derived cryptococcosis. © 2010 by the Infectious Diseases Society of America. All rights reserved.

Patient-reported outcomes following treatment with the human GLP-1 analogue liraglutide or glimepiride in monotherapy: results from a randomized controlled trial in patients with type 2 diabetes

Abstract: Aim: As weight gain and hypoglycaemia associated with glimepiride therapy can negatively impact weight perceptions, psychological well-being and overall quality of life in type 2 diabetes, we investigated whether liraglutide treatment could improve these factors. Methods: Seven hundred and thirty-two patients with type 2 diabetes completed a 77-item questionnaire during a randomized, 52-week, double-blind study with liraglutide 1.2 mg (n = 245) or 1.8 mg (n = 242) compared with glimepiride 8 mg (n = 245). Results: Mean (SE) decreases in glycated haemoglobin levels were greater with liraglutide 1.2 mg [−0.84 (0.08)%] and 1.8 mg [−1.14 (0.08)%] than glimepiride [−0.51 (0.08)%; p = 0.0014 and p < 0.0001, respectively]. Patients gained weight on glimepiride [mean (SE), 1.12 (0.27) kg] but lost weight on liraglutide [1.2 mg: −2.05 (0.28) kg; 1.8 mg: −2.45 (0.28) kg; both p < 0.0001]. Patient weight assessment was more favourable with liraglutide 1.8 mg [mean (SE) score: 40.0 (2.0)] than glimepiride [48.7 (2.0); p = 0.002], and liraglutide 1.8 mg patients were 52% less likely to feel overweight [odds ratio (OR) 0.48; 95% confidence interval (CI): 0.331–0.696]. Mean (SE) weight concerns were less with liraglutide [1.2 mg: 30.0 (1.2); 1.8 mg: 32.8 (1.2)] than glimepiride [38.8 (1.2); p < 0.0001 and p < 0.001, respectively], with liraglutide groups 45% less likely to report weight concern (OR 0.55, 95% CI: 0.41–0.73). Mean (SE) mental and emotional health and general perceived health improved more with liraglutide 1.8 mg [476.1 (2.8) and 444.2 (3.2), respectively] than glimepiride [466.3 (2.8) and 434.5 (3.2), respectively; p = 0.012 and p = 0.033, respectively]. Conclusions: Improved glycaemic control and decreased weight with liraglutide 1.8 mg vs. glimepiride can improve psychological and emotional well-being and health perceptions by reducing anxiety and worry associated with weight gain.

History of right heart catheterization: 100 years of experimentation and methodology development.

Abstract: The development of right heart catheterization has provided the clinician the ability to diagnose patients with congenital and acquired right heart disease, and to monitor patients in the intensive care unit with significant cardiovascular illnesses. The development of bedside pulmonary artery catheterization has become a standard of care for the critically ill patient since its introduction into the intensive care unit almost 40 years ago. However, adoption of this procedure into the mainstream of clinical practice occurred without prior evaluation or demonstration of its clinical or cost-effectiveness. Moreover, current randomized, controlled trials provide little evidence in support of the clinical utility of pulmonary artery catheterization in the management of critically ill patients. Nevertheless, the right heart catheter is an important diagnostic tool to assist the clinician in the diagnosis of congenital heart disease and acquired right heart disease, and moreover, when catheter placement is proximal to the right auricle (atria), this catheter provides an important and safe route for administration of fluids, medications, and parenteral nutrition. The purpose of this manuscript is to review the development of right heart catheterization that led to the ability to conduct physiologic studies in cardiovascular dynamics in normal individuals and in patients with cardiovascular diseases, and to review current controversies of the extension of the right heart catheter, the pulmonary artery catheter.

Periorbital and orbital cellulitis.

Abstract: 1. Andrea Hauser, MD* 2. Simone Fogarasi, MD† 1. *Pediatric Hospitalist, New Orleans Children's Hospital, New Orleans, La. 2. †Pediatric Hospitalist, Ochsner Medical Center, New Orleans, La. After completing this article, readers should be able to: 1. Recognize the difference between periorbital and orbital cellulitis on the basis of history and physical examination findings. 2. Describe the cause, pathophysiology, and management of periorbital and orbital cellulitis. 3. Understand the importance of sinus disease in both periorbital and orbital cellulitis. 4. Know the indications for computed tomography scan and specialist consultation for eyelid swelling. 5. Recognize the complications of periorbital and orbital cellulitis. A 19-month-old boy presents with a 1-day history of left eyelid swelling. The swelling is greater in the lower lid and accompanied by local erythema, tenderness, and temperature up to 38.4°C. His parents state that he has decreased appetite and activity. For the past week, the boy has been experiencing clear, watery rhinorrhea, sneezing, and a mild cough. Today, he was given diphenhydramine without any improvement of the eyelid swelling. His parents deny any history of trauma or recent insect bites to the face. The past medical history is significant for mild intermittent asthma and allergic rhinitis. He is exposed to tobacco at home. On physical examination, the child appears ill, but not toxic. His temperature is 36.9°C, heart rate is 123 beats/min, respiratory rate is 26 breaths/min, and blood pressure is 117/82 mm Hg. Both upper and lower left eyelids appear significantly edematous, with surrounding erythema and tenderness to light touch. No chemosis or proptosis is apparent. Extraocular movements and visual acuity can be evaluated only partially due to pain. Infections of the eye occur in the pediatric population and may present with complaints of eyelid swelling and pain. Expeditious and proper diagnosis is essential because there is …

Usefulness of Precordial T-Wave Inversion to Distinguish Arrhythmogenic Right Ventricular Cardiomyopathy from Idiopathic Ventricular Tachycardia Arising from the Right Ventricular Outflow Tract

Abstract: The 2 predominant causes of ventricular tachycardia (VT) arising from the right ventricle are arrhythmogenic right ventricular cardiomyopathy (ARVC) and idiopathic VT arising from the right ventricular outflow tract (RVOT). These arrhythmias can be adrenergically mediated and may be difficult to distinguish clinically. A minor criterion for the diagnosis of ARVC is T-wave inversion (TWI) in the right precordial leads during sinus rhythm. However, there have been reports of precordial TWI identified in patients with RVOT tachycardia. The purpose of this study was to determine whether patterns of precordial TWI could differentiate between the 2 groups. A multicenter registry of 229 patients with VT of right ventricular origin was evaluated. After appropriate exclusions (n = 29), 79 patients (58% men, mean age 40 ± 14 years) had ARVC, and 121 patients (41% men, mean age 48 ± 14 years) had RVOT tachycardia. During sinus rhythm, 37 patients (47%) with ARVC and 5 patients (4%) with RVOT tachycardia had TWI in leads V 1 to V 3 . For the diagnosis of ARVC, TWI in leads V 1 to V 3 had sensitivity of 47% and specificity of 96%. In conclusion, in patients with VT of right ventricular origin, the presence of TWI in electrocardiographic leads V 1 to V 3 supports the diagnosis of ARVC.

Mitochondrial aldehyde dehydrogenase mediates vasodilator responses of glyceryl trinitrate and sodium nitrite in the pulmonary vascular bed of the rat.

Abstract: It has been reported that mitochondrial aldehyde dehydrogenase (ALDH2) catalyzes the formation of glyceryl dinitrate and inorganic nitrite from glyceryl trinitrate (GTN), leading to an increase in cGMP and vasodilation in the coronary and systemic vascular beds. However, the role of nitric oxide (NO) formed from nitrite in mediating the response to GTN in the pulmonary vascular bed is uncertain. The purpose of the present study was to determine if nitrite plays a role in mediating vasodilator responses to GTN. In this study, intravenous injections of GTN and sodium nitrite decreased pulmonary and systemic arterial pressures and increased cardiac output. The decreases in pulmonary arterial pressure under baseline and elevated tone conditions and decreases in systemic arterial pressure in response to GTN and sodium nitrite were attenuated by cyanamide, an ALDH2 inhibitor, whereas responses to the NO donor, sodium nitroprusside (SNP), were not altered. The decreases in pulmonary and systemic arterial pressure in response to GTN and SNP were not altered by allopurinol, an inhibitor of xanthine oxidoreductase, whereas responses to sodium nitrite were attenuated. GTN was ∼1,000-fold more potent than sodium nitrite in decreasing pulmonary and systemic arterial pressures. These results suggest that ALDH2 plays an important role in the bioactivation of GTN and nitrite in the pulmonary and systemic vascular beds and that the reduction of nitrite to vasoactive NO does not play an important role in mediating vasodilator responses to GTN in the intact chest rat.

Value of Weight Reduction in Patients with Cardiovascular Disease

Abstract: Obesity is an independent risk factor for cardiovascular (CV) disease and contributes markedly to individual CV risk factors, including hypertension, diabetes mellitus, dyslipidemia, and other chronic conditions, such as osteoarthritis, obstructive sleep apnea, and physical deconditioning. Obesity, defined as a body mass index ≥30 kg/m2, is associated with increased morbidity and mortality, particularly in severely obese patients with a body mass index ≥35 kg/m2. Physical activity, healthy eating and behavioral modification are three pivotal approaches to treating obesity. Some individuals may benefit from pharmacologic agents to achieve meaningful weight loss. Unfortunately, there are few such agents at present with proven efficacy and safety profiles. In this review, we discuss the obesity epidemic and its detrimental effects on the CV system, and focus on exercise training and on established pharmacologic agents as well as those on the horizon. We conclude by summarizing the surgical therapeutic options available to treat obesity and the evidence supporting the CV benefits of surgery, and discuss the potential adverse effects of both pharmacologic and surgical options.

Derivation and characterization of an extra-axial chordoma cell line (EACH-1) from a scapular tumor.

Abstract: Background: Extra-axial chordomas are rare low-grade malignant tumors thought to arise from notochordal remnants in the extra-axial skeleton. Few studies have been done on this neoplasm because of its rarity. In addition, there is a lack of a good in vitro model on which to perform more characterization. Methods: We describe a twenty-eight-year-old man with a mass in the right scapula. Cytomorphology and immunohistochemistry, including brachyury staining, were used to formulate the final diagnosis. A fragment of the tumor was placed in culture, and cells obtained were injected subcutaneously in an immunocompromised mouse. From the tumor developed in mice, a cell line has been derived and characterized by fluorescence-activated cell-sorting analysis, karyotyping, clonogenicity, and cell and tumor growth curves. Results: Cytomorphology on the tumor showed nests of round cells with vacuoles and also physaliferous-like cells with uniform nuclei. Immunochemistry revealed a tumor positive for vimentin, moderately positive for S-100 and cytokeratin AE1/AE3, weakly positive for epithelial membrane antigen, and negative for p63 and cytokeratin (CK)-7. Further analysis revealed the tumor was diffusely and strongly positive for brachyury. The cell line derived from the tumor showed rapid doubling-time, a strong expression of mesenchymal cell surface markers, a karyotype of diploid or hypotetraploid clones with numerous chromosomal aberrations, and the ability to form colonies without attachment and to form tumors in immunocompromised mice. Conclusions: The diagnosis of the extra-axial chordoma is difficult but can be resolved by the detection of a strong brachyury expression. In addition, the derivation of a human extra-axial chordoma cell line could be a useful tool for the basic research of this rare neoplasm. Clinical Relevance: We describe the importance of brachyury staining in the diagnosis of this tumor. The extra-axial chordoma cell line (EACH-1) may also provide a new research tool to establish new ways of diagnosing and treating this rare malignancy.

Pulmonary and systemic vasodilator responses to the soluble guanylyl cyclase stimulator, BAY 41-8543, are modulated by nitric oxide

Abstract: BAY 41-8543 is a nitric oxide (NO)-independent stimulator of soluble guanylyl cyclase (sGC). Responses to intravenous injections of BAY 41-8543 were investigated under baseline and elevated tone co...

Cleaned, Ready-to-Use, Reusable Electrocardiographic Lead Wires as a Source of Pathogenic Microorganisms

Abstract: Background Cleaned electrocardiographic lead wires are a potential source of microorganisms capable of causing nosocomial infection. Objectives To examine fungal and bacterial growth on cleaned reusable lead wires, determine if microbial growth is associated with hospital site or work environment, determine the prevalence of antibiotic-resistant bacteria, and learn if antibiotic-resistant bacteria are associated with hospital site and work environment. Methods Cleaned lead wires (N = 320) from critical care and telemetry units, emergency departments, and operating rooms of 4 hospitals were swabbed and the specimens cultured for microbial growth. Bacterial species were grouped by their risk for human infection: at risk (n = 9), potential risk (n = 5), and no risk (n = 10). Work environments were compared by using pairwise contrasts from a generalized estimating equation model. Results Fungi were rare (0.6%). Of 226 cultures from 201 wires (62.8%) with bacterial growth, 121 were of at- or potential-risk bacteria (37.8%). Urban hospitals had less growth (P ≤ .001) and fewer bacterial species per wire (P ≤ .001) than did community hospitals. Presence of any bacteria (P = .02) and number of bacterial species per wire (P = .002) were lowest in operating rooms; emergency departments and telemetry units had more growth than did critical care units. Among specimens of staphylococci and enterococci, 6 each were sensitive to antibiotics; of 4 resistant staphylococcal species, 1 was not a human opportunistic pathogen and 3 were potential-risk species. Conclusions Bacteria are common on reusable, cleaned lead wires and differ by hospital and clinical area.

Cutaneous manifestations of tuberous sclerosis.

Abstract: Purpose: To describe a case of periungual masses probably related to tuberous sclerosis and to review the literature regarding tuberous sclerosis, including the historical, clinical, and diagnostic aspects. Also discussed is the long-term follow-up of the disease. Methods: Report of a case of periungual masses secondary to tuberous sclerosis and review of the literature from 1999 to 2009, with the use of MEDLINE (National Library of Medicine). Results: I describe a case of periungual masses occurring as a result of tuberous sclerosis. A literature review confirms periungual masses associated with tuberous sclerosis in most cases. Also, the observance of cutaneous manifestations is most helpful in the diagnosis of this disorder. Conclusion: Tuberous sclerosis is an uncommon disorder, which has a variable clinical presentation. Tuberous sclerosis is associated with seizures and mental retardation. In the absence of these 2 signs/symptoms, physicians should still consider the diagnosis when presented with varied dermatologic conditions.

To B or not to B: is non-high-density lipoprotein cholesterol an adequate surrogate for apolipoprotein B?

Abstract: During the past 2 decades, considerable progress has been made in establishing the lipid hypothesis and the importance of lipid profiles, especially the levels of lowdensity lipoprotein cholesterol (LDL-C) but also levels of high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs), for predicting risk of coronary heart disease (CHD). Additionally, many large-scale randomized controlled studies of lipid intervention, especially with the statin family of medications, have established the role of improving lipid levels, particularly levels of LDL-C, for CHD risk reduction. However, despite the use of the highest doses of the most potent statins, many patients continue to have major cardiovascular (CV) events (or “residual risk”). In this issue of , Harper and Jacobson point out that, despite considerable evidence supporting focused efforts to reduce LDL-C in primary and secondary CHD prevention, this strategy has many limitations. Clearly, other lipid parameters, including TGs, HDL-C, total cholesterol/HDL ratio and, especially, non–HDL-C, may also be important for predicting CV outcomes in patients receiving LDL-C–lowering therapies. Harper and Jacobson’s commentary particularly emphasizes the potential role of apolipoprotein (apo) B to predict clinical risk and to serve as a target of therapy, providing suggestions for the routine measurement of apo B and using this measurement in efforts to optimize medical intervention. We do not dispute that levels of apo B are strongly related with CHD risk, which has also been argued for many To B or Not to B: Is Non–High-Density Lipoprotein Cholesterol an Adequate Surrogate for Apolipoprotein B?

Elevated Osteopontin Levels in Metastatic Melanoma Correlate with Epigenetic Silencing of Breast Cancer Metastasis Suppressor 1

Abstract: Objective: Breast cancer metastasis suppressor 1 (BRMS1) has been shown to functionally reduce the metastatic potential of melanoma. We also previously reported that BRMS1 negatively regulates the expression of the oncoprotein osteopontin (OPN). This study was carried out to assess the clinical relevance of BRMS1 and OPN in melanoma. Methods: Epigenetic regulation of BRMS1 was assessed by treating clinically derived melanoma cell lines with the demethylating agent 5-aza-2′-deoxycytidine (DAC) and the histone deacetylase inhibitor trichostatin A (TSA), followed by sodium bisulfite modification and methylation-specific PCR. Assessments of BRMS1 and OPN levels were performed using immunoblotting, quantitative real-time RT-PCR or reporter assays. RNA silencing was employed to abrogate the expression of OPN in melanoma-derived cell lines. The in vivo relevance of our findings was determined with experiments using athymic nude mice. Results: The reduced expression of BRMS1 in surgically excised melanoma specimens correlated with increased OPN expression during the progression from primary to metastatic melanoma. Treatment with DAC and TSA elevated BRMS1 levels, but caused an inconsistent change in OPN gene expression. Abrogating the expression of OPN in BRMS1-deficient metastatic melanoma-derived cell lines retarded the growth of melanoma tumor xenografts in athymic nude mice. Conclusion: While treatment with DAC and TSA may not be a universally applicable treatment alternative in melanoma, silencing the expression of OPN in metastatic melanomas that have lost expression of BRMS1 is a potential option for therapeutic intervention.

What is the appropriate extent of lateral neck dissection in the treatment of metastatic well-differentiated thyroid carcinoma?

Abstract: Diagnosis is the basis not only for the management of clinical disorders but also for defining their occurrence in the community and identifying targets for prevention. More broadly, diagnostic terms are part of the language with which we communicate our data, our ideas and our conclusions to colleagues worldwide. In the mental health and substance use disorders fields, diagnoses are made predominantly on the basis of the definitions of these disorders in two major international diagnostic and classification systems. These are the Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Classification of Diseases (ICD). These two international systems are undergoing revision at present, with projected publication dates of 2012 and 2014, respectively. This fact is of significance to those working in the area of substance use disorders, whether they be clinicians, epidemiologists, researchers or policy advisers. The present review focuses on papers published during 2005 and 2006 on the issues of diagnosis, with a particular focus on a series of papers published as part of theDSM-V research agenda-setting process [1–20].

Doing what's right for the resuscitated.

Abstract: In the current issue of Catheterization and Cardiovascular Interventions, Kern and Rahman review the available data supporting percutaneous coronary intervention (PCI) in patients resuscitated from out-of-hospital cardiac arrest (OHCA). They tabulate the results of 17 reports with a total of 930 post-cardiac arrest (PCA) patients, who underwent early cardiac catheterization along with appropriate revascularization and another four case series in which a total of 150 PCA patients were treated with therapeutic hypothermia in addition to early coronary intervention. Survival-to-discharge rates were 60% in the first group and 70% in the second with very high rates (87% and 81%, respectively) of intact neurologic function among survivors. These are remarkably high figures when applied to a population whose expected survival has been only 25%, half of whom have significant neurologic impairment. The authors further point out the unreliability of chest pain and electrocardiographic abnormalities in predicting acute coronary occlusion as the inciting event in these patients. They conclude that the induction of mild therapeutic hypothermia and early coronary angiography/PCI should be strongly considered for all comatose PCA patients regardless of their postresuscitation electrocardiographic findings, a recommendation already made by the International Liaison Committee on Resuscitation in its 2008 Post-Cardiac Arrest Syndrome Consensus Statement [1]. Mounting evidence suggests that therapeutic hypothermia combined with early cardiac catheterization should be adopted as a systematic strategy for PCA patients. Two sentinel randomized-controlled trials published in 2002 [2,3] demonstrated benefits in mortality and neurologic outcome in survivors of OHCA who were treated with therapeutic hypothermia. The publication of these studies brought renewed vigor to the field of resuscitation science, which for decades had struggled for a method to better outcomes. In recent years, the concept of the ‘‘post-cardiac arrest syndrome’’ and how we might further improve this very high-risk subgroup’s odds of survival have received great attention [1]. Many national and international medical societies, including the American Heart Association (AHA), have updated their guidelines recommendations to incorporate therapeutic hypothermia in the treatment of OHCA [4], and a Policy Statement on Regional Systems of Care for OHCA issued by the AHA in January, 2010 specifically addresses the need for early PCI in this population [5]. So what are the obstacles? One is the persistent perception by institutions and physicians that the cardiac arrest survivor has a nearhopeless prognosis [6,7] and that decisions regarding further aggressive care such as coronary intervention should be delayed until the patient has demonstrated adequate promise of neurologic recovery. In fact, available data suggest that currently employed methods of neurologic prognostication are unreliable in the early stages of post-arrest care [6,8]. This is particularly true in patients treated with therapeutic hypothermia [9]. Kern and Rahman’s review of almost 1,100 patients, 150 of whom were treated with hypothermia, suggests significantly better-than-expected outcomes are achievable if these patients are managed aggressively. The solution to this obstacle is education of healthcare providers and hospitals on a national level to change the perception of OHCA from a diagnosis with uniformly negative outcomes to one of hope, which can be positively influenced by improvements in care. Another obstacle is the current enthusiasm for ‘‘score carding’’ for quality outcomes. Hospitals and

Role of the RhoA/Rho-kinase pathway in the regulation of pulmonary vasoconstrictor function

Abstract: Calcium is the major intracellular messenger that triggers smooth muscle contraction. The study of calcium-binding proteins, such as calmodulin and its downstream effectors, reveals critical regulation of smooth muscle contraction by protein kinases and phosphatases. Moreover, the small GTP-binding protein RhoA and its downstream effector protein, Rho-kinase, have been shown to play a novel role in the regulation of smooth muscle contraction. Studies have shown that the activation of Rho-kinase is involved in the development of endothelial dysfunction, inflammation, restenosis, and increased vascular tone in a number of cardiovascular disorders. Because inhibitors of this pathway promote vasodilation independent of the mechanism that increases vasoconstrictor tone, it is our hypothesis that Rho-kinase is constitutively active in regulating vasoconstrictor tone in the pulmonary and systemic vascular beds. Studies in the literature suggest that the RhoA/Rho-kinase pathway has an important role in the pathog...

Maximal Exercise Electrocardiographic Responses and Coronary Heart Disease Mortality Among Men With Metabolic Syndrome

Abstract: OBJECTIVE To examine the association between abnormal exercise electrocardiographic (E-ECG) test results and mortality (all-cause and that resulting from coronary heart disease [CHD] or cardiovascular disease [CVD]) in a large population of asymptomatic men with metabolic syndrome (MetS). PATIENTS AND METHODS A total of 9191 men (mean age, 46.9 years) met the criteria of having MetS. All completed a maximal E-ECG treadmill test (May 14, 1979, through April 9, 2001) and were without a previous CVD event or diabetes at baseline. Main outcomes were all-cause mortality, mortality due to CHD, and mortality due to CVD. Cox regression analysis was used to quantify the mortality risk according to E-ECG responses. RESULTS During a follow-up of 14 years, 633 deaths (242 CVD and 150 CHD) were identified. Mortality rates and hazard ratios (HRs) across E-ECG responses were the following: for all-cause mortality: HR, 1.36; 95% confidence interval (CI), 1.09-1.70 for equivocal responses and HR, 1.41; 95% CI, 1.12-1.77 for abnormal responses ( P trend P trend P trend P CONCLUSION Among men with MetS, an abnormal E-ECG response was associated with higher risk of all-cause, CVD, and CHD mortality. These findings underscore the importance of E-ECG tests to identify men with MetS who are at risk of dying.