Is there a role for Chlamydia pneumoniae infection in systemic lupus erythematosus and in the associated atherosclerotic cardiovascular disease?

OBJECTIVE: To search for molecular evidence of Chlamydial infection in systemic lupus erythematosus (SLE) subjects and to assess if there is an association of this infectious agent with coronary artery calcification (CAC), a marker of total atherosclerotic burden. METHODS: 28 SLE subjects had blood samples drawn and DNA extracted from peripheral blood mononuclear cells (PBMC) and an electron beam computed tomography (EBCT) scan. Polymerase chain reaction (PCR) analysis was performed for Chlamydia trachomatis 16srRNA and major outer membrane protein (MOMP) and for C. pneumoniae 16srRNA, MOMP, as well as nested PCR for MOMP. RESULTS: Four of 28 subjects (14.2%) had evidence of C. pneumoniae nucleic acid in PBMC. The 16srRNA primers detected C. pneumoniae in one patient (3.57%) and the nested PCR MOMP primers in 3 subjects (10.71%). None were positive for Chlamydia trachomatis. Two of the 4 subjects with C. pneumoniae DNA had abnormal EBCT scans and 2/11 (18.3%) subjects with abnormal EBCT were positive for C. pneumoniae. There were significant associations of C. pneumoniae DNA with smoking (OR = 3) and corticosteroid use. The odds ratio for subjects with abnormal CAC and detectable C. pneumoniae was 1.67. CONCLUSION: This pilot study demonstrates for the first time that C. pneumoniae DNA can be identified in the PBMC of some SLE subjects and there may be an association with CAC. Smoking may be an additional risk factor for infection in this population. Determination of pathogenicity of this organism in atherosclerotic coronary vascular disease in SLE will require further study.     

SR calcium depletion following reversal of the Na+/Ca2+-exchanger in rat ventricular myocytes

We previously reported that cytosolic calcium transiently increases after reversal of the sarcolemmal Na+/Ca2+-exchanger. Calcium released from sarcoplasmic reticulum (SR) constituted the major part of this cytosolic transient. The aim of this study was to test whether reversal of the Na+/Ca2+-exchanger affects SR calcium content, and whether altered SR calcium content is associated with direct triggering of SR calcium release or calcium release secondary to SR calcium overload. To this purpose we studied the change of SR calcium content after reversal of the Na+/Ca2+-exchanger and the dependence on the magnitude of change of its free energy (delta Gexch) in isolated rat ventricular myocytes. The Na+/Ca2+-exchanger was reversed by abrupt reduction of extracellular sodium ([Na+]o). The magnitude of change of deltaGexch was varied with [Na+]o. Cytosolic free calcium ([Ca2+]i) was measured with indo-1 and SR calcium content was estimated from the increase of [Ca2+]i after rapid cooling (RC). SR function was manipulated either by blockade of the SR Ca2+-ATPase with thapsigargin or by blockade of SR calcium release channels with tetracaine. Reversal of the Na+/Ca2+-exchanger caused a transient increase of [Ca2+]i of about 180 s duration with a time to peak of about 30 s. During the first 30 s rapid small amplitude cytosolic calcium fluctuations were superimposed on this transient. The magnitude of the response of [Ca2+]i to RC, during the course of the cytosolic [Ca2+]i transient, also transiently increased from 174 in control myocytes to 480 nmol/l at the time of the peak value. After correction of [Ca2+]i data for the fraction of mitochondrially compartmentalized indo-1 and mitochondrial calcium, total calcium released from SR after RC was calculated with the use of literature data on cytosolic calcium buffer capacity. Contrary to the measured RC-dependent increase of measured [Ca2+]i, after reversal of the Na+/Ca2+-exchanger, calculated total calcium released from SR transiently decreased. The extent of SR calcium depletion after reversal of the Na+/Ca2+-exchanger increased with the magnitude of change of deltaGexch. Restitution of [Na+]o 30 s after reversal of the Na+/Ca2+-exchanger, greatly accelerated both recovery of [Ca2+]i and SR calcium content. Pretreatment of myocytes with thapsigargin caused almost entire depletion of SR and substantial reduction of the cytosolic transient of [Ca2+]i following reversal of the Na+/Ca2+-exchanger. Application of tetracaine hardly affected SR calcium content, but caused an increase of the SR calcium content following reversal of the Na+/Ca2+-exchanger, while the cytosolic transient increase of [Ca2+]i was substantially reduced. We conclude that reversal of the Na+/Ca2+-exchanger directly triggers SR calcium release and decreases SR calcium content in a deltaGexch dependent manner.     

Pathways to Colonoscopy in the South: Seeds of Health Disparities

Objectives. We aimed to highlight sociodemographic differences in how patients access colonoscopy.Methods. We invited all eligible patients (n = 2500) from 2 academy-affiliated colonoscopy centers in Alachua County, Florida (1 free standing, 1 hospital based), to participate in a precolonoscopy survey (September 2011–October 2013); patients agreeing to participate (n = 1841, response rate = 73.6%) received a $5.00 gift card.Results. We found sociodemographic differences in referral pathway, costs, and reasons associated with obtaining the procedure. Patients with the ideal pathway (referred by their regular doctor for age-appropriate screening) were more likely to be Black (compared with other minorities), male, high income, employed, and older. Having the colonoscopy because of symptoms was associated with being female, younger, and having lower income. We found significant differences for 1 previously underestimated barrier, having a spouse to accompany the patient to the procedure.Conclusions. Patients’ facilitators and barriers to colonoscopy differed by sociodemographics in our study, which implies that interventions based on a single facilitator will not be effective for all subgroups of a population.Colorectal cancer (CRC), the second leading cause of US cancer deaths in 2013 (50 830),1 is not distributed equally. Nationally, it is estimated that incidence is 25% higher, and mortality from CRC 50% higher, in Black Americans than in Whites.2,3 Most CRC diagnoses follow evaluation by colonoscopy. Although consumers have a range of CRC screening tests, from least invasive (fecal occult blood test, fecal immunochemical test) to most invasive (sigmoidoscopy, colonoscopy),4 if polyps are indicated, a colonoscopy is required as follow-up. Thus, colonoscopy is both an entry point and a pivotal event in the process of preventing, detecting, and treating CRC. CRC can be prevented through the removal of precancerous polyps or detected at an early, easily treatable stage5; findings indicate6 that colonoscopy with polypectomy reduces mortality from CRC by 53%. Although rates of CRC screening have increased,3 there is need for improvement. More than one third of Americans are not in compliance with screening guidelines,7 with rates being lower in the southern United States.8In 2008, Etzioni et al.9 presented a model of patient and provider-level factors that influence decision-making in colon cancer and that can lead to health disparities in disease recurrence and survival. The Etzioni model identifies key points of vulnerability in the treatment process where the potential to achieve high-quality, guideline-recommended care can be lost. The model captures patients after surgery, beginning with the decision to refer patients to a medical oncologist for adjuvant treatment; it is relevant because there is considerable evidence of inequities in who receives adjuvant treatment based on older age,10,11 comorbidities,12,13 low income,7 coverage with Medicaid rather than Medicare,13 Black race,14 female gender,15,16 and being unmarried.9We propose that this model starts too late in the process; health disparities originate prior to colonoscopy and can increase at each decision point along a continuum. In an elaborated model (Figure 1), we suggest that CRC health disparities research should begin with an investigation of entry into the health care system and the subsequent pathways to colonoscopy. Referral patterns, costs, and patient demographics influence patient access to care, colonoscopy compliance, and postcolonoscopy decision-making.Open in a separate windowFIGURE 1—Pathways to colonoscopy, treatment, and outcomes.     

Feasibility of Recruiting Families into a Heart Disease Prevention Program Based on Dietary Patterns

Offspring of parents with a history of cardiovascular disease (CVD) inherit a similar genetic profile and share diet and lifestyle behaviors. This study aimed to evaluate the feasibility of recruiting families at risk of CVD to a dietary prevention program, determine the changes in diet achieved, and program acceptability. Families were recruited into a pilot parallel group randomized controlled trial consisting of a three month evidence-based dietary intervention, based on the Mediterranean and Portfolio diets. Feasibility was assessed by recruitment and retention rates, change in diet by food frequency questionnaire, and program acceptability by qualitative interviews and program evaluation. Twenty one families were enrolled over 16 months, with fourteen families (n = 42 individuals) completing the study. Post-program dietary changes in the intervention group included small daily increases in vegetable serves (0.8 ± 1.3) and reduced usage of full-fat milk (−21%), cheese (−12%) and meat products (−17%). Qualitative interviews highlighted beneficial changes in food purchasing habits. Future studies need more effective methods of recruitment to engage families in the intervention. Once engaged, families made small incremental improvements in their diets. Evaluation indicated that feedback on diet and CVD risk factors, dietetic counselling and the resources provided were appropriate for a program of this type.