Chlamydia and associated arthritis

An inflammatory arthritis is known to follow urogenital infection with the intracellular bacterium Chlamydia trachomatis in some individuals, and recent research results have elucidated important aspects of the characteristics of this Chlamydia-associated joint disease. Although the several extra-articular features of Chlamydia-induced arthritis have been defined clinically, their detailed causes remain largely unexplained. Current data indicate that the clinical characteristics of joint disease associated with C. trachomatis infection and those associated with postenteric arthritis are not easily distinguishable, although the response of each to antibiotic therapy does differ. The biologic characteristics of Chlamydia and enteric organisms in the joint show profound differences, and these are probably responsible for the variable responses to drug treatment. Molecular analyses of synovial C. trachomatis have demonstrated that long-term infection of the joint occurs primarily in synovial tissue and that the organism exhibits highly unusual biologic properties in its synovial context. These unusual molecular, biochemical, and other characteristics provide explanations for the frequent culture negativity of joint materials for C. trachomatis and for several other aspects of the arthritogenic process. Much remains to be learned concerning the behavior of this organism in the joint and concerning its interaction with its synovial host cells.     

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.     

Monosodium urate crystals in the knee joints of patients with asymptomatic nontophaceous gout

We aspirated synovial fluid from the knees of 50 patients with asymptomatic, nontophaceous gout, in whom synovial fluid monosodium urate (MSU) crystals had previously been documented in the knees or other joints. Fifty-eight percent of these asymptomatic patients had MSU crystals in their knee joints. Serum uric acid levels, serum creatinine levels, volume of synovial fluid aspirated, and cell counts of the aspirated fluid did not differentiate the MSU crystal-positive group from the group without MSU crystals. Clinical factors such as alcohol abuse, coronary heart disease, hypertension, duration of gout, duration of the intercritical period, and drug therapy did not differentiate the 2 groups. Nineteen patients consented to aspiration of their other knee. Seven of these patients (37%) had MSU crystals bilaterally, and 6 patients (32%) had them unilaterally. The implications of the persistence of MSU crystals (including those in intracellular locations) in many patients, despite normalization of serum uric acid levels, should be determined. Knee joint aspiration is a sensitive method for the demonstration of MSU crystals in asymptomatic patients. The procedure might also be useful in documenting these crystals in patients who have had attacks of arthritis with features consistent with a diagnosis of gout, but in whom MSU crystals have not been documented.     

Platelet-activating factor and the release of a platelet-derived coronary artery vasodilator substance in the canine

Platelet-activating factor (acetyl-glyceryl-ether-phosphorylcholine; 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphorylcholine), which is released by stimulated neutrophils and platelets, possesses the ability to alter vascular tone and permeability and to activate various formed blood elements. We have characterized the hemodynamic effects of intracoronary injections of platelet-activating factor and the influences of pharmacological blockade and platelet depletion on its activity. Intracoronary injections of platelet-activating factor produced maximum increases in left circumflex coronary artery blood flow of 55 +/- 8, 52 +/- 8, and 52 +/- 7 ml/min at 0.5, 1.0, and 2.0 nM, respectively. Only modest changes in systemic arterial blood pressure and regional developed isometric contractile force were associated with the intracoronary artery administration of platelet-activating factor over the range of doses studied. The increase in left circumflex coronary artery blood flow in response to platelet-activating factor was attenuated (44%), but not prevented, by pretreatment with diphenhydramine, (4 mg/kg, iv), and was not affected by pretreatment with aspirin (20 mg/kg, iv) or the systemic administration of the serotonin receptor antagonist, methysergide. The coronary vasodilator response to platelet-activating factor was reduced significantly by the induction of thrombocytopenia (95 +/- 3% platelet depletion) through the administration of sheep-derived canine platelet antiserum. The intracoronary artery injection of platelet-rich plasma activated with platelet-activating factor into thrombocytopenic dogs produced a significantly greater increase in coronary artery blood flow than the injection of either non-activated platelet-rich plasma or platelet-depleted plasma to which platelet-activating factor was added. Similar changes in coronary artery blood flow could be obtained with the intracoronary artery injection of cell-free supernates from washed platelets activated with platelet-activating factor. The observed results suggest that circulating platelets, when exposed to platelet-activating factor, can release a coronary dilator substance, and that the coronary artery dilation is not prevented by pharmacological receptor antagonists for histamine, serotonin, or inhibitors of cyclooxygenase.     

Calcium apatite crystals in synovial fluid rice bodies

BACKGROUND: Rice bodies can occur in the joints in many rheumatic conditions, but they are most common in rheumatoid arthritis. They are generally believed to occur rarely in patients with osteoarthritis, but one study reported rice bodies with apatite crystals. OBJECTIVE: To report on a series of joint fluids with rice bodies containing apatite clumps and examine their clinical pictures. Methods: All synovial fluid analysis reports for 10 years were reviewed for rice bodies and eight patients were reported on. A series of patients with a variety of diseases with synovial fluid rice bodies found to contain calcific material is described. All were examined by compensated polarised light and alizarin red stain, and four were examined by electron microscopy. RESULTS: The eight patients all had alizarin red S chunks embedded throughout the rice body. Transmission electron microscopy disclosed the presence of a matrix of collagen, fibrin, and amorphous materials containing typical apatite crystals. Clinical diagnoses, radiographic findings, and leucocyte counts varied, but six of the eight patients had had previous repeated corticosteroid injections into the joints. CONCLUSION: Aggregates of apatites may be more common than previously recognised in rice bodies as they are not routinely sought. Whether they are a result of joint damage or depot steroid injections and whether that might contribute to further joint injury now needs to be investigated.