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ID PMID Title PublicationDate abstract
20641497 [(18)F]-5-(2-fluoroethyl)2,4-diethyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxyl 2004 Adenosine is an important signaling molecule that is involved in several pathophysiological conditions such as asthma, inflammation, and neurodegeneration. It is known to mediate its effects through four G-protein–coupled receptors, A(1), A(2) (with sub types A(2A) and A(2B)), and A(3) (the receptors are also designated as A1AR, A2AR, and A3AR, respectively) in the mammalian system. These receptors have been identified in several human tissues and, because they play a role in different pathologies, are targeted for the clinical development of a variety of drugs (2, 3). Much information is available regarding the function and tissue distribution of the A(1) and A(2A) receptors; however, because of a lack of proper agonists and antagonists to study the A(2B) and A(3) receptors, the exact role of the latter two receptors in mammalian physiology is not clear (4). In addition to its possible involvement in the development of rheumatoid arthritis and brain, lung, and cardiac ischemia, the A(3) receptor was shown to be overexpressed and had a proliferative effect in certain cancer tissues and cell lines (5-7). Although this receptor is known to be involved in a number of diseases, little is known about its expression and distribution in the different regions and tissue of the body (4). In an attempt to study the ligand binding properties of the A(3) receptor, investigators developed antagonistic pyridine analogs that showed high affinity and specificity for the receptor (8, 9). Among these pyridine compounds, a fluoroethyl ester derivative, 5-(2-fluoroethyl)2,4-diethyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxylate (FE@SUPPY), was determined to have a high affinity and selectivity for the A(3) receptor (9). Recently, Wadsak et al. developed a suitable precursor for the synthesis of FE@SUPPY and labeled the A(3) ligand with radioactive fluorine ((18)F) to obtain [(18)F]FE@SUPPY (4). The labeled compound was subsequently studied for its biodistribution in rats and its specificity was determined by autoradiography. The metabolic properties of [(18)F]FE@SUPPY were compared to those of its analogue, [(18)F]FE@SUPPY:2 (5-ethyl-2,4-diethyl-3-((2-[(18)F]fluoroethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxylate), in rodents by Haeusler et. al. (1). To compare the structures of [(18)F]FE@SUPPY and [(18)F]FE@SUPPY:2 see (1).
20641699 (99m)Tc-labeled anti-tumor necrosis factor-alpha monoclonal antibody. 2004 The tumor necrosis factor alpha (TNF-α) is synthesized as a 26-kDa membrane-bound protein on certain cell types, e.g., T cells. The membrane-bound protein is cleaved to release a 17-kDa soluble form that exists as a homotrimer. It has been implicated in the pathogenesis of different diseases including cancer and inflammatory diseases such as rheumatoid arthritis (RA), Crohn’s disease (CD), and ulcerative colitis (1, 2). The stimulation of TNF-α induction is known to activate several pro-inflammatory cytokines, chemokines, matrix metalloproteinases, and endothelial adhesion molecules that attract cells known to promote inflammation (3). Because of its role in the pathogenesis of different inflammatory diseases, a variety of anti–TNF-α agents have been developed and investigated for the treatment of these conditions (4). Several anti–TNF-α antibodies such as infliximab, adalimumab, and certolizumab are now available for the treatment of TNF-α–mediated inflammatory diseases (2). Infliximab is an anti–TNF-α, chimeric mouse-human IgG1 monoclonal antibody (mAb) that is commercially available and is approved by the United States Food and Drug Administration for the treatment of a variety of inflammatory diseases (2, 4). This mAb is known to bind TNF-α in the serum or on the cell membranes and to inhibit its biological activity mediated through the TNF-α receptor. To evaluate its in vivo use for the detection of TNF-α in the various inflammatory diseases, infliximab was labeled with radioactive meta-stable technetium ((99m)Tc) and used as detailed below (2, 5-7).
19096562 Clinical experiences and usefulness of cervical posterior stabilization with polyaxial scr 2007 Oct OBJECTIVE: The objective of this study is to investigate the safety, surgical efficacy, and advantages of a polyaxial screw-rod system for posterior occipitocervicothoracic arthrodesis. METHODS: Charts and radiographs of 32 patients who underwent posterior cervical fixation between October 2004 and February 2006 were retrospectively reviewed. Posterior cervical polyaxial screw-rod fixation was applied on the cervical spine and/or upper thoracic spine. The surgical indication was fracture or dislocation in 18, C1-2 ligamentous injury with trauma in 5, atlantoaxial instability by rheumatoid arthritis (RA) or diffuse idiopathic skeletal hyperostosis (DISH) in 4, cervical spondylosis with myelopathy in 4, and spinal metastatic tumor in 1. The patients were followed up and evaluated based on their clinical status and radiographs at 1, 3, 6 months and 1 year after surgery. RESULTS: A total of 189 screws were implanted in 32 patients. Fixation was carried out over an average of 3.3 spinal segment (range, 2 to 7). The mean follow-up interval was 20.2 months. This system allowed for screw placement in the occiput, C1 lateral mass, C2 pars, C3-7 lateral masses, as well as the lower cervical and upper thoracic pedicles. Satisfactory bony fusion and reduction were achieved and confirmed in postoperative flexion-extension lateral radiographs and computed tomography (CT) scans in all cases. Revision surgery was required in two cases due to deep wound infection. One case needed a skin graft due to necrotic change. There was one case of kyphotic change due to adjacent segmental degeneration. There were no other complications, such as cord or vertebral artery injury, cerebrospinal fluid leak, screw malposition or back-out, or implant failure, and there were no cases of postoperative radiculopathy due to foraminal stenosis. CONCLUSION: Posterior cervical stabilization with a polyaxial screw-rod system is a safe and reliable technique that appears to offer several advantages over existing methods. Further biomechanical testings and clinical experiences are needed in order to determine the true benefits of this procedure.
16449313 Membrane glucocorticoid receptors are down regulated by glucocorticoids in patients with s 2006 Sep BACKGROUND: Membrane-bound glucocorticoid receptors (mGCR) are up regulated on monocytes after in vitro stimulation and in patients with rheumatoid arthritis. Caveolin-1 is critical for the transport of plasma membrane oestrogen receptors to the cell surface. OBJECTIVES: To investigate the expression of mGCR in patients with systemic lupus erythematosus (SLE)-a disease with different aetiopathogenesis and treatment regimens-and to examine whether caveolin-1 is critical for the transport of mGCR to the cell surface. METHODS: Frequencies of mGCR+ peripheral blood mononuclear cells were measured using high-sensitivity immunofluorescent staining and tested for correlation with SLE disease activity and glucocorticoid treatment. Semiquantitative polymerase chain reaction, immunofluorescence, recombinant expression and confocal laser-scanning microscopy were used to search for an association of mGCR with caveolin-1. RESULTS: The frequencies of mGCR+ monocytes (CD14+) were considerably higher in patients with SLE (n = 33) than in healthy controls (n = 58), whereas B cells (CD19+) were not different in this regard. T cells (CD3+) were always mGCR-. The frequency of mGCR+ monocytes in patients with SLE did not correlate with disease activity, but did inversely correlate with glucocorticoid dosages; this inverse correlation was confirmed by corresponding in vitro experiments with stimulated monocytes. The induced up regulation of mGCR was not accompanied by an up regulation of caveolin-1, and mGCR are not colocalised with caveolin-1 in plasma membrane caveolae. CONCLUSION: mGCR are (a) up regulated in patients with SLE and by inflammatory stimuli and (b) down regulated by glucocorticoids, suggesting a negative feedback loop to control glucocorticoid action. Drugs binding selectively to mGCR may in future prove to be of therapeutic value.
18694865 Hypothalamic-pituitary-adrenal axis in patients with ankylosing spondylitis. 2008 Jul OBJECTIVE: To investigate the hypothalamic-pituitary-adrenal (HPA) axis via the insulin-tolerance test (ITT), standard-dose (250 microg) ACTH test (SDT) and low-dose (1 microg) ACTH test (LDT) in patients with ankylosing spondylitis (AS). DESIGN: The study group included 13 male patients with AS who were diagnosed according to the Modified New York criteria, and 8 healthy male subjects and was carried out at the Department of Physical Medicine and Rehabilitation, Erciyes University Medical School. ACTH stimulation tests were carried out by using 1 microg and 250 microg i.v. ACTH as a bolus injection, and blood samples were drawn at 0, 30 and 60 min. ITT was performed by using intravenous (i.v.) soluble insulin, and serum glucose and cortisol levels were measured before and after 30, 60, 90 and 120 min. All of the tests were performed consecutively with 3-day intervals, after an overnight fast. RESULTS: There were no significant differences between the patients with AS (mean age 36.9+/-6.7 years) and the healthy subjects (mean age 37.4+/-5.7 years) in terms of age. The basal cortisol levels in the AS group measured during LDT, SDT and ITT (556+/-204 nmol/l; 524+/-169 nmol/l; 418+/-232 nmol/l, respectively) were comparable to the values of the control group (572+/-199 nmol/l; 520+/-182 nmol/l; 424+/-194 nmol/l, respectively). There were also no significant differences in peak cortisol responses between the two groups using LDT (patients 1025+/-339 nmol/l; controls 844+/-236 nmol/l), SDT (patients 1082+/-243 nmol/l; controls 1120+/-131 nmol/l) and ITT (patients 834+/-256 nmol/; controls 820+/-239 nmol/). CONCLUSION: In contrast with findings in other inflammatory diseases such as rheumatoid arthritis and polymyalgia rheumatica, the present data indicate that there is no apparent abnormality of the HPA axis activity in patients with AS.
18612638 A population-based study of prevalence and hospital charges in total hip and knee replacem 2009 Aug The purpose of this study was to explore the increasing prevalence of factors affecting hospital charges for primary total hip replacement/total knee replacement (THR/TKR). This study analysed 37,918 THR and 76,727 TKR procedures performed in Taiwan from 1996 to 2004. Odds ratio (OR) and effect size (ES) were calculated to assess the relative change rate. Multiple regression models were employed to predict hospital charges. The following factors were associated with increased hospital charges: age younger than 65 years old; increased disease severity (Charlson comorbidity index [CCI] = 1 or > or = 2); absence of primary diagnoses of osteoarthritis (OA), rheumatoid arthritis (RA), avascular necrosis (AVN); treatment at a hospital or by a surgeon performing a high volume of operations; and longer average length of stay (ALOS). The Bureau of National Health Insurance (BNHI) should ensure that surgeons take precautionary measures to minimise complications and maximise quality of life after surgery. Use of joint prostheses from different manufacturers can reduce costs without compromising patient satisfaction.
18426802 Induction of cytosolic calcium flux by CD20 is dependent upon B Cell antigen receptor sign 2008 Jun 20 The anti-CD20 monoclonal antibody (mAb) rituximab is now routinely used for the treatment of non-Hodgkins lymphoma and is being examined in a wide range of other B-cell disorders, such as rheumatoid arthritis. Despite intensive study, the mechanism of action still remains uncertain. In the current study, anti-CD20 mAb-induced calcium signaling was investigated. Previously, we grouped anti-CD20 mAbs into Type I (rituximab-like) and Type II (B1-like) based upon various characteristics such as their ability to induce complement activation and redistribute CD20 into detergent-insoluble membrane domains. Here we show that only Type I mAbs are capable of inducing a calcium flux in B cells and that this is tightly correlated with the expression of the B-cell antigen receptor (BCR). Inhibitor analysis revealed that the signaling cascade employed by CD20 was strikingly similar to that utilized by the BCR, with inhibitors of Syk, Src, and PI3K, but not EGTA, p38, or ERK1/2, completely ablating calcium flux. Furthermore, binding of Type I but not Type II mAbs caused direct association of CD20 with the BCR as measured by FRET and resulted in the phosphorylation of BCR-specific adaptor proteins BLNK and SLP-76. Crucially, variant Ramos cells lacking BCR expression but with unchanged CD20 expression were completely unable to induce calcium flux following ligation of CD20. Collectively, these data indicate that CD20 induces cytosolic calcium flux through its ability to associate with and "hijack" the signaling potential of the BCR.
18292540 Abnormal NF-kappa B function characterizes human type 1 diabetes dendritic cells and monoc 2008 Mar 1 Dendritic cell (DC) differentiation is abnormal in type 1 diabetes mellitus (T1DM). However, the nature of the relationship between this abnormality and disease pathogenesis is unknown. We studied the LPS response in monocytes and monocyte-derived DCs isolated from T1DM patients and from non-T1DM controls. In T1DM patients, late LPS-mediated nuclear DNA binding by RelA, p50, c-Rel, and RelB was impaired as compared with type 2 DM, rheumatoid arthritis, and healthy subjects, associated with impaired DC CD40 and MHC class I induction but normal cytokine production. In TIDM monocytes, RelA and RelB were constitutively activated, and the src homology 2 domain-containing protein tyrosine phosphatase (SHP-1), a negative regulator of NF-kappaB, was overexpressed. Addition of sodium stibogluconate, a SHP-1 inhibitor, to DCs differentiating from monocyte precursors restored their capacity to respond to LPS in approximately 60% of patients. The monocyte and DC NF-kappaB response to LPS is thus a novel phenotypic and likely pathogenetic marker for human T1DM. SHP-1 is at least one NF-kappaB regulatory mechanism which might be induced as a result of abnormal inflammatory signaling responses in T1DM monocytes.
18289055 Matrix metalloproteinase-9/gelatinase B is a putative therapeutic target of chronic obstru 2008 Feb Matrix metalloproteinases (MMPs) are a large family of proteolytic enzymes involved in an array of physiological and pathological processes from development, morphogenesis, reproduction, wound healing, and aging to inflammation, angiogenesis, neurological disorders, and cancer cell invasion and metastasis. The imbalance between MMP activity and the inhibitory action of tissue inhibitors of metalloproteinases (TIMPs) are implicated in multiple diseases. Secreted in the body in a latent form, upon activation MMP-9 (gelatinase B) acts on many inflammatory substrates, and thus is suspected of contributing to the progression of cardiovascular disease, rheumatoid arthritis, and the subjects of this review, chronic obstructive pulmonary disease (COPD) and multiple sclerosis (MS). COPD is the fourth most common cause of death in the United States. In COPD, increased expression of MMP-9 by inflammatory cells e.g. neutrophils and macrophages is correlated with a variety of processes that cause lung damage. MMP-9 is also important in cytokine and protease modulation; it degrades the serine protease inhibitor alpha(1)-antitrypsin, which thus may lead to lung destruction. MS affects approximately 400,000 Americans and over a million people worldwide. Upregulation of MMP-9 increases the permeability of the blood brain barrier (BBB), facilitates the infiltration of leukocytes into the central nervous system, and causes myelin sheath degradation and neuronal damage. Early stage clinical trials have shown promising results when MMP-9 is inhibited in MS. These observations lead to the hypothesis that MMP-9 is a potential drug target for both COPD and MS and further development of highly potent and specific MMP-9 inhibitors is warranted.
18283522 Prevalence of disease-specific antinuclear antibodies in general population: estimates fro 2008 The aim of this study was to investigate the types and prevalence of disease-specific antinuclear antibodies (ANAs) and their relationship to rheumatic diseases in the general Japanese population. An immunofluorescence (IF) method was used for the first screening of ANA levels in serum samples obtained from 2181 residents of a small Japanese town. Individuals positive for IF-ANA were then further tested for disease-specific ANAs using eight enzyme immunoassays. Physical status and the presence of illness were determined by means of questionnaires and medical examinations. Based on the result of the IF-ANA assay, the rates of positive samples at 1:40 and 1:160 dilutions were 26.0 and 9.5%, respectively, with females have significantly higher positivity rates than males (P < 0.0001). Among 566 IF-ANA-positive individuals, 100 individuals were found to have 114 disease-specific ANAs. Anti-SSA/Ro, anti-centromere, and anti-U1RNP antibodies were detected in 58, 30, and 11 individuals, respectively, but anti-Sm, anti-Scl-70, and anti-Jo-1 antibodies were undetectable. Questionnaires and medical examinations revealed that among 60 disease-specific ANA-positive individuals that were available for testing, six had Sjögren's syndrome (SS), five were suspected of having SS, and five had rheumatoid arthritis. Surprisingly, 34 (57%) of the disease-specific ANA-positive individuals were clinically healthy. Anti-SSA/Ro, anti-centromere, and anti-U1RNP antibodies were quite frequent among clinically healthy Japanese subjects, although anti-Sm, anti-Scl-70, and anti-Jo-1 antibodies were not. Of the 60 individuals who tested positive for disease-specific ANAs, 30% (18/60) actually manifested systemic rheumatic diseases, while 50% showed no detectable signs or symptoms of rheumatic diseases.
18218304 Reversible primary hypothyroidism in Japanese patients undergoing maintenance hemodialysis 2008 Feb BACKGROUND/METHODS: The presence or absence of hypothyroidism was assessed in 152 consecutive Japanese patients with end-stage renal disease on hemodialysis. Eight patients who had undergone treatment for thyroid disease before starting hemodialysis therapy, and 3 patients with amyloidosis due to rheumatoid arthritis were excluded. RESULTS: Of the remaining 141 hemodialysis patients, 14 (9.9%) (9 males and 5 females, aged 69.1 A+/- 8.8 years with a mean duration of hemodialysis of 69 A+/- 51 months) were in a hypothyroid state, defined as a thyroid-stimulating hormone (TSH) level > 5 mU/l. Antithyroid peroxidase antibodies were positive in only 1 of the 14 patients, while antithyroglobulin antibodies were negative in all of these patients. After iodide restriction, the serum TSH level decreased in all the patients from a mean of 16.49 A+/- 22.80 to 4.44 A+/- 3.35 mU/l after 1 month, 4.25 A+/- 2.24 mU/l after 2 months and 3.97 A+/- 2.22 mU/l after 3 months. The 3 months of iodide restriction were also associated with decreases in systolic blood pressure (142 A+/- 19 to 125 A+/- 16 mmHg, p < 0.05), diastolic blood pressure (79 A+/- 13 to 72 A+/- 9 mmHg, p < 0.05) and thyroid gland volume estimated by ultrasonography (13.7 A+/- 6.3 to 11.6 A+/- 5.2 ml, p < 0.05). CONCLUSION: A high prevalence of reversible primary hypothyroidism was found in end-stage renal disease patients on hemodialysis. Retention of excess iodide may be the mechanism responsible for reversible hypothyroidism rather than immunological perturbations. It is, therefore, recommended to attempt iodide restriction before starting l-thyroxine replacement therapy.
18203315 Effects of etanercept on serum biochemical markers of cartilage metabolism in patients wit 2008 Feb OBJECTIVE: Anti-tumor necrosis factor (TNF) therapies provide symptomatic benefit in patients with spondyloarthropathy (SpA). Their effect on structural lesions has not yet been assessed. Biochemical markers of cartilage turnover revealing type II collagen degradation and synthesis are associated with joint damage in rheumatoid arthritis; their role in SpA is unknown. We describe the effects of etanercept on biochemical markers of type II collagen synthesis and degradation in patients with SpA followed for 2 years. METHODS: A total of 29 patients with SpA aged 22-68 years were included in a prospective 2-year study. Each patient received etanercept (25 mg twice a week) because of active disease despite optimal treatment. Cartilage degradation was investigated by measuring serum levels of the type II collagen fragments Helix-II and C2C, whereas the C-terminal propeptide of type II collagen (PIICP) was used as a marker of type II collagen synthesis. These markers were measured at baseline and after 1, 3, 6, 12, and 24 months of treatment. RESULTS: Over 2 years, there was a significant decrease of serum C2C (p = 0.0035 by repeated Friedman's test) and serum Helix-II (p = 0.004). Compared to baseline, the decrease of serum C2C was significant at Month 12 (-12.1%; p = 0.004), whereas the decrease of serum Helix-II was observed as early as 1 month (-18.1%; p = 0.015) after start of therapy, reaching a maximum decrease of -33.4% (p = 0.0079) at Month 12. Conversely, PIICP increased significantly by 17% (p = 0.006) at 24 months. CONCLUSION: These data suggest that etanercept may have beneficial effects on cartilage metabolism in patients with SpA.
18087008 Incidence and risk factors for psoriasis in the general population. 2007 Dec OBJECTIVES: To study the clinical spectrum of psoriasis and the incidence in the general population and to identify risk factors associated with the occurrence of psoriasis. DESIGN: Prospective cohort study with nested case-control analysis. SETTING: The data source was the United Kingdom General Practice Research Database containing computerized clinical information entered by general practitioners (GPs). PATIENTS: The study population comprised patients receiving a first-ever diagnosis of psoriasis between January 1, 1996, and December 31, 1997, and free of cancer. INTERVENTIONS: Diagnosis of psoriasis was validated in a random sample of 14% of all ascertained cases requesting confirmation by the GPs. Nested case-control analysis included 3994 cases of psoriasis and a random sample of 10 000 controls frequency matched to cases by age, sex, and calendar year. MAIN OUTCOME MEASURES: Incidence rate of psoriasis and estimates of the odds ratio (OR) and 95% confidence interval (CI) for psoriasis as associated with selected risk factors. RESULTS: The incidence rate of psoriasis was 14 per 10 000 person-years. Patients with antecedents of skin disorders and skin infection within the last year carried the highest risk of developing psoriasis (OR, 3.6 [95% CI, 3.2-4.1], and OR, 2.1 [95% CI, 1.8-2.4], respectively). Also, smoking was found to be an independent risk factors for psoriasis (OR, 1.4 [95% CI, 1.3-1.6]). We did not find an association between risk of psoriasis and antecedents of stress, diabetes, hypertension, hyperlipidemia, cardiovascular disease, or rheumatoid arthritis. CONCLUSIONS: The incidence rate in our study was higher than those published in other studies, probably owing to our case definition that considered cases recorded by the GPs independently of a specialist confirmation. Our results confirm the association between psoriasis, skin disorders, and smoking.
18061485 Development of a predictive model for estimating the probability of treatment success one 2008 May OBJECTIVE: To Estimate the probability of treatment success 1 year after a total shoulder arthroplasty by developing a model based on preoperative clinical factors. METHOD: Between June 2003 and December 2006, 140 patients undergoing shoulder operations were assessed for age, gender, current rheumatoid arthritis, Short Form (SF) 36 physical and mental sum scores, previous shoulder operations, the Disabilities of Arm, Shoulder and Hand (DASH) symptom and function scores, the Shoulder Pain and Disability Index (SPADI), and insurance status. One year after the operation a Constant score of 80 or more out of 100 indicated successful treatment. Patient variables were analyzed with a logistic regression model augmented in a stepwise manner and bootstrapped 100 times. Variables selected at least 33 times were incorporated into a final model and the Area under the Receiver Operating Characteristics Curve (aROC) was calculated. RESULTS: There were 47/140 (33.6%) successful treatments. The probability of success was reduced in patients with previous shoulder operations (Odds Ratio [O.R.] 0.17, 95% Confidence Interval (95%CI) 0.04-0.85; P=0.03) and older than 75 years (O.R. 0.21, 95%CI 0.05-0.77; P=0.02). The probability of success increased in patients with a higher SF 36 mental sum score (O.R. 1.03, 95%CI 0.96-1.09, P=0.42) and a higher DASH function score (O.R. 1.05, 95%CI 1.02-1.07, P=0.001). The aROC was 0.79 (0.70-0.88) indicating that the model has a high predictive capacity. CONCLUSION: Once validated this model based on four preoperative clinical factors offers a prediction of whether a patient will respond to treatment 1 year after total shoulder arthroplasty.
17684700 Assessment of laboratory measurements and -308 TNFalpha gene promoter polymorphisms in nor 2008 Mar The aim of this study was to identify and evaluate laboratory parameters associated with normal bone mineral density (BMD) and to test if -308 tumour necrosis factor (TNF) alpha gene promoter polymorphisms could influence BMD. We performed a comparative cross-sectional study of four main groups: young healthy individuals (20-30 years); subjects aged 50 years or over with normal BMD; osteoporotic subjects aged 50 years or over; osteoporotic women with active rheumatoid arthritis. Variables assessed included anthropometric features, diet intake, lifestyle, calcium-phosphorus balance, markers of bone turnover, sexual hormones, hormones related with body mass and growth, cytokines involved in inflammation and bone turnover, and -308 TNF alpha gene promoter polymorphisms. One hundred fifty-nine subjects were evaluated. Across the four groups, zinc serum levels were higher in men as compared to women. In addition, zinc serum levels were also higher in individuals with normal BMD as compared to osteoporotic subjects. Serum calcium levels were higher in normal BMD group. On the other hand, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were significantly higher in normal bone mass postmenopausal women and men as compared to age-matched osteoporotic groups. Finally, leptin was significantly lower in men, after correcting these results for body mass index values. The remaining variables assessed had a similar distribution among the different studied groups. In our population, low serum levels of leptin and high serum levels of zinc, calcium, FSH, and LH were associated with a higher BMD.
17563461 Risk factor paradox in wasting diseases. 2007 Jul PURPOSE OF REVIEW: Emerging data indicate that conventional cardiovascular risk factors (e.g. hypercholesterolemia and obesity) are paradoxically associated with better survival in distinct populations with wasting. We identify these populations and review survival paradoxes and common pathophysiologic mechanisms. RECENT FINDINGS: A 'reverse epidemiology' of cardiovascular risk is observed in chronic kidney disease, chronic heart failure, chronic obstructive lung disease, cancer, AIDS and rheumatoid arthritis, and in the elderly. These populations apparently have slowly progressive to full-blown wasting and significantly greater short-term mortality than the general population. The survival paradoxes may result from the time differential between the two competing risk factors [i.e. over-nutrition (long-term killer but short-term protective) versus undernutrition (short-term killer)]. Hemodynamic stability of obesity, protective adipokine profile, endotoxin-lipoprotein interaction, toxin sequestration of fat, antioxidation of muscle, reverse causation, and survival selection may also contribute. SUMMARY: The seemingly counterintuitive risk factor paradox is the hallmark of chronic disease states or conditions associated with wasting disease at the population level. Studying similarities among these populations may help reveal common pathophysiologic mechanisms of wasting disease, leading to a major shift in clinical medicine and public health beyond the conventional Framingham paradigm and to novel therapeutic approaches related to wasting and short-term mortality.
17388920 Assessment of nailfold capillaroscopy by x 30 digital epiluminescence (dermoscopy) in pati 2007 May BACKGROUND: Dermoscopy is a useful tool for dermatologists to study melanocytic lesions. Its possible usefulness in the assessment of capillary nailfold morphological changes (capillaroscopy) has recently been advocated. OBJECTIVES: To assess the practical utility of digital epiluminescence microscopy as a capillaroscopic instrument in patients with Raynaud phenomenon (RP). To compare the sensitivity and specificity rates obtained by epiluminescence microscopy with those previously reported with conventional capillaroscopic devices. METHODS: Fifty-six consecutive patients with primary RP (PRP; n = 5) or secondary RP (SRP; n = 51) (11 men and 45 women in total) were included in the study. A control group of 10 healthy subjects was also evaluated. Twenty-six patients (46%) had systemic sclerosis (SS), 12 (21%) presystemic sclerosis (pre-SS), one (2%) dermatopolymyositis-SS, one (2%) mixed connective tissue disease, two (4%) Sjögren syndrome, two (4%) an overlap syndrome, one (2%) rheumatoid arthritis and six (11%) other connective tissue diseases. Capillary nailfold changes were studied using a nonportable digital epiluminescence device (magnification x 30). Following a systematized protocol, capillary nailfold morphology, density and distribution were evaluated. Several capillaroscopic patterns were identified (normal, sclerodermic, nonspecific, nondiagnostic) as previously defined. A possible relationship between capillary nailfold changes and the intensity of RP or the presence of associated autoimmune diseases was assessed. RESULTS: The sclerodermic pattern showed a sensitivity of 76.9% and a specificity of 90.9% in SS. A typical capillaroscopic SS pattern was observed in 73% of cases of limited SS and in 82% of cases of diffuse SS. Patients with Sjögren syndrome and dermatopolymyositis-SS showed a nonspecific capillaroscopic pattern. All patients with PRP presented a normal capillaroscopic pattern. A normal capillaroscopic pattern was also observed in 11 of 12 patients with pre-SS. In one of two patients presenting severe sclerodactyly and in all patients showing hand oedema (three of 56), capillaroscopic changes could not be evaluated. Avascular areas correlated significantly with severe RP (P < 0.002), bone resorption (P < 0.007) and diffuse SS (P < 0.008). CONCLUSIONS: Digital epiluminescence seems to be a useful and reliable technique in the evaluation of capillary nailfold morphological changes. This technical variation allows the identification of specific capillaroscopic patterns associated with connective tissue diseases. It also permits us to differentiate PRP from SRP. The results obtained with this technique are similar to those previously reported using standard capillaroscopy devices.
17290723 Correlation of high sensitivity C-reactive protein and calcific aortic valve disease. 2007 Feb OBJECTIVE: To determine whether a difference exists in the levels of high sensitivity C-reactive protein (Hs-CRP) in patients with and without calcific aortic valve disease (CAVD). PATIENTS AND METHODS: This cross-sectional study consisted of 110 patients who had undergone echocardiographic examination from January 2005 to February 2006 at our institution. Information on demographic variables, coronary risk factors, and medications was obtained. More than 200 patients were excluded on the basis of any evidence of infection, active connective tissue disorder, rheumatoid arthritis, recent episodes of bleeding, acute fractures, bowel obstruction, or acute coronary syndrome or use of corticosteroids, nonsteroidal anti-inflammatory drugs, or antibiotic treatment. The values of Hs-CRP, total cholesterol, and erythrocyte sedimentation rate were included. RESULTS: Of the 110 study subjects, 38 patients had aortic sclerosis, 36 patients had aortic stenosis, and 36 were controls. The mean Hs-CRP level in the control group was significantly lower (4.84 +/- 6.9 mg/L) compared with the levels in the groups with aortic sclerosis (14.9 +/- 19.6 mg/L) and aortic stenosis (13.6 +/- 17.3 mg/L) (P = -.01). No statistically significant difference was found between the patients in the aortic sclerosis and aortic stenosis groups. Among the patients with aortic stenosis, no significant correlation existed between Hs-CRP levels and aortic stenosis severity. CONCLUSIONS: The Hs-CRP seems to have a significant association with CAVD during its early stage. The study findings did not have sufficient evidence to suggest the use of Hs-CRP as a marker of progression of calcific aortic stenosis. The Hs-CRP may have a role in identifying patients in the early stages of CAVD and in whom medical treatment may be beneficial to halt the progression to irreversible aortic valvular calcification and stenosis.
17169363 Impaired coronary microvascular and left ventricular diastolic functions in patients with 2008 Jan BACKGROUND: It has been shown that the patients with inflammatory rheumatic diseases such as systemic lupus erythematosus and rheumatoid arthritis have an increased risk of developing atherosclerosis. However, the association of ankylosing spondylitis (AS) to atherosclerosis and related diseases is still controversial. Accordingly, we investigated coronary flow reserve (CFR) and left ventricular (LV) diastolic function in patients with AS using transthoracic Doppler echocardiography. METHODS: CFR and LV diastolic function were studied in 40 patients with AS (38.9+/-10.2 years, 26 males) and 35 healthy volunteers (37.5+/-6.4 years, 23 males). Coronary diastolic peak flow velocities (DPFV) were measured at baseline and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to baseline DPFV. LV diastolic function was assessed by both standard and tissue Doppler imaging. RESULTS: Demographic features and coronary risk factors except diastolic blood pressure were similar between the groups. CFR were significantly lower in the AS group than in the control group (2.20+/-0.46 versus 3.02+/-1.50, P<0.0001). Reflecting LV diastolic function mitral A-wave and E/A ratio were borderline significant, and mitral E-wave deceleration time and isovolumic relaxation time were significantly different between the groups. Serum hsCRP and TNF-alpha levels were significantly higher in the patients with AS, and hsCRP and TNF-alpha levels independently correlated with CFR. CONCLUSION: These findings show that CFR reflecting coronary microvascular function and LV diastolic function are impaired in patients with AS, and severity of these impairments correlate well with hsCRP and TNF-alpha. These results suggest that impaired CFR may be an early manifestation of cardiac involvement in patients with AS.
16893384 Protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene R620W variant and sporadic 2006 Aug Recently, a gain of function variant C1858T of the lymphoid-specific protein tyrosine phosphatase non-receptor (LYP, PTPN22) gene has been reported to be associated with several autoimmune disorders including Graves' disease, type 1 diabetes, rheumatoid arthritis and vitiligo. The present study was carried out in 80 patients with sporadic idiopathic hypoparathyroidism (SIH) [43 males and 37 females, mean +/- SD age and duration of symptoms 32.5 +/- 14.1 years and 6.7 +/- 7.2 years (range 1 day to 35 years), respectively] and 193 healthy controls (male : female ratio 91:102, mean +/- SD age, 43.1 +/- 11.6 years) to assess association of 1858T allele with the disease. Polymerase chain reaction-restriction fragment length polymorphism analysis was performed to genotype C1858T variant. The frequency of occurrence of 1858T allele was 4/160 (2.5%) in SIH and 5/386 (1.3%) in the control alleles (odds ratio 1.95, 95% CI 0.51-7.37). Thus, the present study reveals that 1858T allele is rare (1.3%) in Asian Indians. The trend of higher prevalence of 1858T allele in patients with SIH needs to be studied further in other population with higher rate of the allele to support the autoimmune basis of the disease.