Aberrant expression of cytokine interleukin 9 along with interleukin 4 and interferon γ in connective tissue disease-associated interstitial lung disease: association with severity of pulmonary fibrosis.

INTRODUCTION: Connective tissues diseases (CTDs) are a heterogeneous group of disorders that share certain clinical characteristics and disturbed immunoregulation. Interstitial lung diseases (ILDs), also known as diffuse parenchymal lung diseases, are among the most serious pulmonary complications associated with CTDs. Interleukin 9 (IL-9), IL-4 and interferon γ (IFN-γ) - cytokines with important roles in autoimmune disease - were studied in CTD patients and CTD-ILD patients. MATERIAL AND METHODS: Sixty-one hospitalized untreated CTD patients were recruited, and 20 healthy volunteers were enrolled as controls. The 61 CTD patients were divided into a simple CTD group and a CTD-ILD group, and the plasma protein IL-9, IL-4 and IFN-γ levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The results indicate that the serum IL-9 levels were significantly higher in CTD-ILD and simple CTD patients than they were in healthy controls (each p < 0.05) and that the levels were elevated in CTD-ILD patients compared with simple CTD patients (p < 0.05). The IL-4 levels were higher in CTD-ILD patients than they were in the simple CTD patients (p < 0.05) and healthy controls (p < 0.01). In addition, the serum IL-9 levels were negatively correlated with the level of IFN-γ (r (2) = 0.34, p = 0.01), the estimated percentage of predicted forced vital capacity (FVC%) (r (2) = 0.36, p = 0.00) and the estimated percentage of predicted diffusing capacity (DLCO%) (r (2) = 0.27, p = 0.04) and were positively correlated with the IL-4 level (r (2) = 0.31, p = 0.01). CONCLUSIONS: Interleukin-9 may play an important role in the pathogenesis of CTD and may contribute to the progression of interstitial lung injury in CTD patients.

Prevalence and risk factors for pulmonary arterial hypertension in end-stage renal disease patients undergoing continuous ambulatory peritoneal dialysis.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a major complication in renal failure patients, but very little information is available on the cardiovascular parameters in these patients. The prevalence and risk factors for PAH were systematically evaluated in patients with end-stage renal diseases (ESRD) undergoing continuous ambulatory peritoneal dialysis (CAPD). METHODS: Between January 2010 and January 2014, 177 ESRD patients (85 males and 92 females) undergoing CAPD therapy were recruited. General data, biochemical parameters and echocardiographic findings were collected and PAH risk factors studied. RESULTS: Study participants consisted of 65 patients (36.52%) with PAH (PAH group) and 112 patients without PAH (non-PAH group). The interdialytic weight gain, systolic blood pressure and diastolic blood pressure (DBP), mean arterial pressure and hypertensive nephropathy incidence in the PAH group were significantly higher than the non-PAH group (all p < 0.05). There were significant differences between PAH group and non-PAH group in C-reactive protein-positive rate, N-terminal pro-brain natriuretic peptide (NT-proBNP), hemoglobin, prealbumin and serum albumin levels (all p < 0.05). Compared with non-PAH group, PAH group showed significant increases in right ventricular internal diameter (RVID), right ventricular outflow tract diameter (RVOTD), main pulmonary artery diameter, left atrial diameter (LAD), left ventricular end-diastolic diameter, interventricular septal thickness, left ventricular mass index, early diastolic mitral annulus velocity and valve calcification incidence (all p < 0.05), and decreased left ventricular ejection fraction (LVEF), tricuspid annulus plane systolic excursion (TAPSE) and early diastolic blood flow peak and mitral annulus velocity (E/E') (all p < 0.05). Logistic regression analysis revealed that DBP, NT-proBNP, LAD, RVID, RVOTD, LVEF, TAPSE and E/E' are major risk factors for PAH. CONCLUSION: We observed a high incidence of PAH in ESRD patients undergoing CAPD. Logistic regression analysis revealed that DBP, NT-proBNP, LAD, RVID, RVOTD, LVEF, TAPSE and E/E' are high-risk factors for PAH in ESRD patients undergoing CAPD.

Repetitive Transcranial Magnetic Stimulation Treatment for Chronic Tinnitus: A Randomized Clinical Trial.

IMPORTANCE: Chronic tinnitus negatively affects the quality of life for millions of people. This clinical trial assesses a potential treatment for tinnitus. OBJECTIVES: To determine if repetitive transcranial magnetic stimulation (rTMS) can reduce the perception or severity of tinnitus and to test the hypothesis that rTMS will result in a statistically significantly greater percentage of responders to treatment in an active rTMS group compared with a placebo rTMS group. DESIGN, SETTING, AND PARTICIPANTS: A randomized, participant and clinician or observer-blinded, placebo-controlled clinical trial of rTMS involving individuals who experience chronic tinnitus. Follow-up assessments were conducted at 1, 2, 4, 13, and 26 weeks after the last treatment session. The trial was conducted between April 2011 and December 2014 at Portland Veterans Affairs Medical Center among 348 individuals with chronic tinnitus who were initially screened for participation. Of those, 92 provided informed consent and underwent more detailed assessments. Seventy individuals met criteria for inclusion and were randomized to receive active or placebo rTMS. Sixty-four participants (51 men and 13 women, with a mean [SD] age of 60.6 [8.9] years) were included in the data analyses. No participants withdrew because of adverse effects of rTMS. INTERVENTIONS: Participants received 2000 pulses per session of active or placebo rTMS at a rate of 1-Hz rTMS daily on 10 consecutive workdays. MAIN OUTCOMES AND MEASURES: The Tinnitus Functional Index (TFI) was the main study outcome. Our hypothesis was tested by comparing baseline and posttreatment TFIs for each participant and group. RESULTS: Overall, 18 of 32 participants (56%) in the active rTMS group and 7 of 32 participants (22%) in the placebo rTMS group were responders to rTMS treatment. The difference in the percentage of responders to treatment in each group was statistically significant (χ(1)(2) = 7.94, P < .005). CONCLUSIONS AND RELEVANCE: Application of 1-Hz rTMS daily for 10 consecutive workdays resulted in a statistically significantly greater percentage of responders to treatment in the active rTMS group compared with the placebo rTMS group. Improvements in tinnitus severity experienced by responders were sustained during the 26-week follow-up period. Before this procedure can be implemented clinically, larger studies should be conducted to refine treatment protocols. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01104207.

The effect of renin-angiotensin system inhibitors on intact parathyroid hormone levels in peritoneal dialysis patients.

HYPOTHESIS/INTRODUCTION: The objective of this article is to investigate the effect of renin-angiotensin system inhibitors (RASIs) on intact parathyroid hormone (iPTH) levels in continuous ambulatory peritoneal dialysis (CAPD) patients. MATERIALS AND METHODS: All patients were divided into RASI-treated and non-treated groups. The relationships between the iPTH levels in CAPD patients and the clinical parameters and medication use were analyzed via linear regression. RESULTS: A total of 149 CAPD patients were included in this study. The average iPTH level of the entire group was 189.4 pg/ml (range, 102.8-373.4 pg/ml). There were 79 (53.0%) and 70 (47.0%) cases in the RASI-treated and non-treated groups, respectively, with average iPTH levels of 139.0 pg/ml (range, 91.6-258.4 pg/ml) and 253.0 pg/ml (range, 134.3-467.2 pg/ml), respectively; this difference was statistically significant (p = 0.001). Multilinear regression analysis showed that age, dialysis vintage, serum phosphatemia, ALP, Hb and RASI use were independent factors that were associated with iPTH level. CONCLUSION: RASI use may be associated with a lower iPTH level in CAPD patients, although the underlying mechanism requires further study.

Blockade of macrophage autophagy ameliorates activated lymphocytes-derived DNA induced murine lupus possibly via inhibition of proinflammatory cytokine production.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a typical inflammatory autoimmune disease for its unknown pathogenesis and potential fatality. It has been reported that autophagy has a crosstalk with autoimmunity, but its impact on the pathogenesis of SLE remains unclear. Here, we investigated the role of autophagy in inflammatory response of macrophages under SLE conditions. METHODS: First, we detected the expression of autophagy-related genes (Atg5, Atg12 and Beclin 1) in the macrophages derived from activated lymphocytes-derived DNA (ALD-DNA) induced murine lupus as well as in the PBMC from SLE patients. And then through adoptive transfer of Beclin 1 knockdown macrophages, we further investigated the potential effect of macrophage autophagy on the SLE-associated inflammatory response and disease severity by evaluating serum anti-dsDNA antibodies and proteinuria levels, immune complex deposition as well as renal pathological changes. RESULTS: We found that autophagy related genes were significantly upregulated in the splenic and renal macrophages of lupus mice and in the PBMC of SLE patients. Adoptive transfer of Beclin 1 knockdown macrophages could significantly decrease the anti-dsDNA antibodies and proteinuria levels, robustly reduce renal immune complex deposition and remit glomerulonephritis, indicating the amelioration of murine lupus. This protective effect was associated with the obviously decreased production of proinflammatory cytokines IL-6 and TNF-α. CONCLUSIONS: Our results suggested that aberrant activated autophagy in macrophages contributed to the pathogenesis of murine lupus possibly via promoting the production of proinflammatory cytokines TNF-α and IL-6, and inhibition of autophagy might represent a novel regulation strategy for excessive activation of proinflammatory macrophages and a new therapeutic regime for SLE.

Decreased interleukin 35 and CD4+EBI3+ T cells in patients with active systemic lupus erythematosus.

BACKGROUND: Interleukin 35 (IL-35) is likely to contribute to the development of autoimmune diseases, as the Epstein-Barr virus-induced gene protein 3 (EBI3) is the specificity subunit of IL-35. Nevertheless, until recently, no studies have evaluated its role in systemic lupus erythematosus (SLE) in humans. The objective of this study was to investigate the serum IL-35 level and the percentage of CD4EBI3 T cells in the peripheral blood of patients with SLE and explore the roles of double-positive T cells and IL-35 in the pathogenesis of SLE and the effects of glucocorticoid on these roles. METHODS: Fifty-five hospitalized patients with SLE were recruited, and 20 volunteers were enrolled as healthy controls. Serum IL-35 levels were measured by enzyme-linked immunosorbent assay, and the percentage of CD4EBI3 T cells was analyzed by flow cytometry. RESULTS: The serum IL-35 level and the percentage of CD4EBI3 T cells were significantly decreased in patients with active SLE compared with healthy controls and patients with inactive SLE. The serum IL-35 level and the percentage of CD4EBI3 T cells were negatively correlated with the SLE disease activity index. The percentages of CD4EBI3 T cells and serum IL-35 levels in 10 untreated patients with active SLE were increased at days l, 3, and 7 after the treatment with methylprednisolone (0.8 mg·kg·d) compared with the percentages before the treatment. CONCLUSIONS: These results demonstrate that abnormalities in IL-35 and CD4EBI3 T cells may play important roles in the pathogenesis of SLE; the percentage of double-positive T cells and the level of IL-35 are parameters for the evaluation of SLE activity and severity.

Hydrogen sulfide ameliorates high-glucose toxicity in rat peritoneal mesothelial cells by attenuating oxidative stress.

BACKGROUND/AIMS: Continuous exposure of the peritoneal membrane to high-glucose (HG) peritoneal dialysis fluids (PDFs) can produce peritoneal mesothelial cells (PMCs) injury. It has been demonstrated that hydrogen sulfide (H2S), the third endogenous gaseous mediator identified after nitric oxide and carbon monoxide, exhibits a potent protective effect on cell activity. We studied the toxic effects of HG PDFs and their reversal by H2S on cultures of rat PMCs. METHODS: Synchronized confluent rat PMCs were incubated with 2.5% glucose PDFs with or without NaHS, an H2S donor. Cell viability was assessed by methyl thiazolyl tetrazolium assay and flow cytometry. The level of phospho-p38 mitogen-activated protein kinase (MAPK) was analyzed by immunoblotting. p53, Bax and Bcl-2 mRNA expressions by rat PMCs were detected by real-time PCR. The levels of reactive oxygen species (ROS), superoxide dismutase (SOD) activity and caspase-3 activity were measured. RESULTS: Exposure of rat PMCs to 2.5% glucose PDFs for 24 h resulted in a significant induction of apoptosis, which was attenuated by NaHS. NaHS also restored the 2.5% glucose PDF-induced increase in phospho-p38 MAPK (indices of cellular toxicity). Further investigation of the apoptotic mechanisms in rat PMCs demonstrated that HG activated caspase-3 and upregulated Bax, while it downregulated Bcl-2. All the above responses were prevented by pretreatment with NaHS. Moreover, NaHS reversed the 2.5% glucose PDF-induced increase in ROS generation and decrease in SOD activity. CONCLUSIONS: These findings suggest that HG PDFs significantly inhibit rat PMC viability, leading to peritoneal injury. H2S exhibits a potent anti-apoptotic ability by attenuating oxidative stress and inhibiting caspase-3 activation, which in turn restores peritoneal injury.

Medical management of tinnitus: role of the physician.

Tinnitus is a common auditory complaint that can be caused by many auditory as well as nonauditory systems diseases. Comorbidities including insomnia, anxiety, and depression are common in severe tinnitus. Other factors such as personality characteristics and socioeconomic difficulties can also contribute to tinnitus distress. Management of tinnitus therefore requires diagnosis and treatment expertise by physicians to adequately address existing etiologies and comorbidities, as well as relevant expertise by nonphysician specialists such as audiologists and psychologists. In assessing the efficacy of tinnitus treatments, nonspecific effects such as placebo effects must be taken into consideration. Management of complex tinnitus cases often requires a multidisciplinary team approach. Physicians and nonphysician specialists need to promptly refer patients to relevant specialist colleagues for adequate evaluation and treatment when such needs are present.

Experimental, controversial, and futuristic treatments for chronic tinnitus.

BACKGROUND: Because chronic tinnitus is a condition that negatively impacts the quality of life of millions of people worldwide, a safe and effective treatment for tinnitus has been sought for millennia. However, effective treatments for tinnitus are greatly outnumbered by ineffective strategies, medications, devices, and surgeries that continue to be developed and promoted for the condition. PURPOSE: This article describes and critiques experimental, controversial, and potential treatments for chronic tinnitus. The purpose of this review is to provide information that should help patients and clinicians to select tinnitus treatment and management strategies most likely to be effective for each set of symptoms and circumstances. RESEARCH DESIGN: PubMed and MEDLINE databases (National Center for Biotechnology Information, U.S. National Library of Medicine) were searched for the term tinnitus in articles published from 1940 to 2012. Other historical documents and publications were also reviewed as needed for particular topics. STUDY SAMPLE: Studies included in this review were selected to represent a sampling of treatment methodologies that have been used for tinnitus. DATA COLLECTION AND ANALYSIS: Due to the heterogeneity of the studies reviewed, it was not appropriate to perform a meta-analysis. A selective review of the literature was conducted to summarize and critique published research results. RESULTS: Most invasive treatments for tinnitus should be avoided because (1) at best, there is scant evidence that any of these treatments is effective, and (2) the risk to patients for most invasive procedures is much greater than the risk posed by the tinnitus perception. Effective and noninvasive treatments for tinnitus include acoustic therapy (which includes hearing aids and other types of environmental sound enrichment); cognitive-behavioral therapy; psychological counseling; hypnosis; biofeedback; and relaxation training. Over-the-counter or prescription medications may be used as needed to facilitate sleep and to reduce anxiety, depression, or obsessive-compulsiveness. CONCLUSIONS: Patients and clinicians should be especially cautious when considering invasive (and potentially harmful) treatments for tinnitus, which is a non-life-threatening symptom. Unless well-designed clinical trials verify that a tinnitus therapy demonstrates effectiveness above and beyond the placebo effect, consumers should be wary of medications, devices, or procedures promoted as a "cure." Although a true cure for tinnitus has not yet been found, effective and noninvasive tinnitus management strategies are available now. If progress is made to medically (or genetically) treat sensorineural hearing loss in humans, this breakthrough should also help to simultaneously reduce the perception of tinnitus for many patients.

Leriche syndrome masquerading as chronic kidney disease.

Renal artery stenosis is causative in 2 - 5% patients with hypertension and accounts for 3 - 15% cases of chronic kidney disease (CKD). The affected renal artery is usually occluded by an atheromatous plaque in the elderly or by Takayasu arteritis in younger women. In comparison, occlusion caused by a chronic thrombus is uncommon. Leriche syndrome refers to the chronic thrombotic occlusion of the terminal abdominal aorta and the surrounding branches. This syndrome normally affects infrarenal arteries and chances of involving renal arteries are rare. We report a case of Leriche syndrome manifesting as chronic kidney disease, while its characteristic symptom-claudication is absent.

Hydrogen sulfide inhibits the renal fibrosis of obstructive nephropathy.

Hydrogen sulfide has recently been found decreased in chronic kidney disease. Here we determined the effect and underlying mechanisms of hydrogen sulfide on a rat model of unilateral ureteral obstruction. Compared with normal rats, obstructive injury decreased the plasma hydrogen sulfide level. Cystathionine-ß-synthase, a hydrogen sulfide-producing enzyme, was dramatically reduced in the ureteral obstructed kidney, but another enzyme cystathionine-γ-lyase was increased. A hydrogen sulfide donor (sodium hydrogen sulfide) inhibited renal fibrosis by attenuating the production of collagen, extracellular matrix, and the expression of α-smooth muscle actin. Meanwhile, the infiltration of macrophages and the expression of inflammatory cytokines including interleukin-1ß, tumor necrosis factor-α, and monocyte chemoattractant protein-1 in the kidney were also decreased. In cultured kidney fibroblasts, a hydrogen sulfide donor inhibited the cell proliferation by reducing DNA synthesis and downregulating the expressions of proliferation-related proteins including proliferating cell nuclear antigen and c-Myc. Further, the hydrogen sulfide donor blocked the differentiation of quiescent renal fibroblasts to myofibroblasts by inhibiting the transforming growth factor-ß1-Smad and mitogen-activated protein kinase signaling pathways. Thus, low doses of hydrogen sulfide or its releasing compounds may have therapeutic potentials in treating chronic kidney disease.

SUMOylation of PPARγ by rosiglitazone prevents LPS-induced NCoR degradation mediating down regulation of chemokines expression in renal proximal tubular cells.

Rosiglitazone (RGL), a synthetic agonist for peroxisome proliferator activated receptor γ (PPARγ), exhibits a potent anti-inflammatory activity by attenuating local infiltration of neutrophils and monocytes in the renal interstitium. To evaluate the mechanisms that account for inhibiting inflammatory cells infiltration, we investigated the effect of RGL on chemokines secretion and nuclear factor-kappa B (NF-κB) activation in human renal proximal tubular cells (PTCs). We demonstrated that RGL significantly inhibited lipopolysaccharide (LPS)-induced interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) production in a dose-dependent manner, without appreciable cytotoxicity. Chromatin immunoprecipitation (ChIP) assays clearly revealed that, RGL inhibited p65 binding to IL-8/MCP-1 gene promoters in LPS-stimulated PTCs. Interestingly, further experiments showed RGL reversed LPS-induced nuclear receptor corepressor (NCoR) degradation. In addition, knockdown of protein inhibitor of activated STAT1 (PIAS1), an indispensable small ubiquitin-like modifier (SUMO) ligase, abrogated the effects of RGL on antagonizing LPS-induced IL-8/MCP-1 overexpression and NCoR degradation. These findings suggest that, RGL activates PPARγ SUMOylation, inhibiting NCoR degradation and NF-κB activation in LPS-stimulated PTCs, which in turn decrease chemokines expression. The results unveil a new mechanism triggered by RGL for prevention of tubular inflammatory injury.

Risk factor analysis of calcification in aortic and mitral valves in maintenance peritoneal dialysis patients.

BACKGROUND/AIMS: This study aimed to investigate potential risk factors for calcification in aortic and mitral valves in maintenance peritoneal dialysis (MPD) patients. METHODS: We enrolled MPD patients who had undergone over 18 months of dialysis in our dialysis center, examined their cardiac valve calcification status by echocardiography, and recorded their biochemical data and dialysis-related indicators. These results were compared by logistic regression analyses to identify the risk factors associated with calcification in aortic and mitral valves. RESULTS: Among the 117 enrolled MPD patients, 41 exhibited calcification in aortic or mitral valves, including 38 with aortic valve calcification (AVC) and 17 with mitral valve calcification (MVC); 14 of them had calcification in both aortic and mitral valves. Multivariate logistic regression analysis revealed that age (OR=1.965, p=0.01), diabetes history (OR=4.693, p=0.029), calcium-phosphorus product (OR=2.373, p=0.001) and prealbumin (OR=0.908, p=0.012) were independently related to AVC, whereas age (OR=3.179, p=0.023), calcium-phosphorus product (OR=6.512, p=0.001), prealbumin (OR=0.885, p=0.033), high-density lipoprotein (OR=19.540, p=0.011) and diabetes history (OR=6.948, p=0.038) were independently related to MVC. CONCLUSIONS: The incidence of cardiac valve calcification in MPD patients is high, and the incidence of AVC is higher than MVC. Age, diabetes history, calcium-phosphorus product and hypo-prealbuminemia are independent risk factors for AVC, whereas age, calcium-phosphorus product and hypo-prealbuminemia are independent risk factors for MVC.

Uric acid levels and all-cause mortality in peritoneal dialysis patients.

BACKGROUND: Epidemiological studies have shown that hyperuricemia is associated with all-cause and cardiovascular mortality in chronic kidney disease (CKD) and hemodialysis patients. Our study investigated the influence of serum uric acid (UA) levels on survival in peritoneal dialysis (PD) patients. METHODS: This was a retrospective study involving 156 subjects who had undergone PD. The patient demographics, etiology of ESRD, comorbid conditions and other laboratory parameters were collected. The subjects were divided into three groups according to their serum UA concentrations (group 1, the lowest quartile; group 2, the middle quartiles; group 3, the highest quartile). The risk of death was calculated using a multivariate Cox regression model. RESULTS: There were 41 deaths during a follow-up period of 31.3±17.5 months. Compared with group 2, which had a mortality rate of 5.7 per 1000 person-months, the mortality rates were higher in group 1 (14.3 per 1000 person-months, p<0.05) and group 3 (13.3 per 1000 person-months, p<0.05). A multivariable Cox regression model revealed that age, serum albumin, diabetes mellitus (DM), hypertensive nephropathy, residual renal function and UA group were factors associated with mortality in the PD patients. Using group 2 as a reference, the hazard ratio (HR) of mortality was found to be 1.15 (95% confidence interval [CI] 0.20-2.57, p>0.05) for group 1 and 2.96 (95% CI 1.29-6.80, p=0.01) for group 3. CONCLUSIONS: In PD patients, a higher serum UA level is related to increased mortality and is an independent risk factor for all-cause mortality. Uric acid levels and all-cause mortality in peritoneal dialysis patients.

[Abnormality and significance of interleukin-9 and CD4(+)interleukin-9(+) T-cells in peripheral blood of patients with systemic lupus erythematosus].

OBJECTIVE: To examine the protein and mRNA levels of interleukin-9(IL-9) and the frequencies of CD4(+)IL-9(+)T-cells in peripheral blood of patients with systemic lupus erythematosus (SLE) and explore the roles of double positive T cells and IL-9 in the pathogenesis of SLE and the effects of glucocorticoid. METHODS: Twenty-eight hospitalized SLE patients were recruited and 12 healthy volunteers selected as normal controls. The mRNA levels of IL-9 in peripheral blood were measured by real time-polymerase chain reaction (RT-PCR), plasma protein of IL-9 by enzyme-linked immunosorbent assay (ELISA) and frequencies of CD4(+)IL-9(+)T-cells by flow cytometry. And the differences between two groups and the effects of glucocorticoid were analyzed. RESULTS: (1) The mRNA levels of IL-9 were significantly elevated in SLE patients as compared with normal controls (P < 0.01). The serum levels of IL-9 were significantly higher in active and inactive SLE patients than those in healthy individuals (68 ± 11 vs 26 ± 6 ng/L, P < 0.01; 56 ± 14 vs 26 ± 6 ng/L, P < 0.05). The percentages of CD4(+)IL-9(+)T-cells increased in active SLE patients (1.96% ± 0.31%) versus inactive SLE patients (0.89% ± 0.13%, P < 0.01) and healthy controls (0.28% ± 0.05%, P < 0.001). And it was higher in inactive SLE patients than that in controls (P < 0.05). (2) The serum levels of IL-9 and the frequencies of CD4(+)IL-9(+)T-cells were positively correlated with SLE disease activity index (SLEDAI). (3) The frequencies of CD4(+)IL-9(+)T-cells and the serum levels of IL-9 in 8 untreated active SLE patients decreased at weeks 1, 2 and 3 after the therapy of methylprednisolone (0.8 mg×kg(-1)×d(-1)) versus those at pre-treatment. CONCLUSION: The abnormalities of IL-9 and CD4(+)IL-9(+)T-cells may play an important role in the pathogenesis of SLE. And the frequencies of CD4(+)IL-9(+)T-cells and the levels of IL-9 are evaluative parameters of SLE activity and severity.

Increased interleukin­9 and CD4+IL-9+ T cells in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown origin affecting all the organ systems. Apart from genetic and environmental factors, autoantibody and immune complex deposition as well as cytokine imbalances contribute to immune dysfunction. Interleukin­9 (IL-9) is a T cell-derived factor preferentially expressed by CD4+ T cells and it has been characterized in human and murine systems. IL-9 targets cells of the lymphoid, myeloid and mast cell lineages, and is likely to contribute to the development of allergic and autoimmune diseases such as asthma, arthritis, multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Nevertheless, until recently there have been no studies on its role in SLE in humans. In the present study, the mRNA and serum IL-9 levels in the peripheral blood of SLE patients and healthy controls were assessed using real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Flow cytometry was used to analyze the percentages of CD4+IL-9+ T cells in SLE patients. Moreover, differences between the groups and the effect of glucocorticoids were analyzed. The results showed that the plasma concentration and mRNA levels of IL-9 were significantly elevated in SLE patients compared with the healthy controls. The percentages of CD4+IL-9+ T cells were also increased in SLE patients. In addition, serum IL-9 levels and the percentages of CD4+IL-9+ T cells were correlated with the SLE disease activity index (SLEDAI). Additionally, the percentages of CD4+IL-9+ T cells and serum IL-9 levels in 8 untreated active SLE patients were decreased at 1, 2 and 3 weeks after treatment with methylprednisolone. In conclusion, we provide evidence that IL-9 is increased in SLE patients. Moreover, it is described for the first time that high expression of IL-9 levels and the percentages of CD4+IL-9+ T cells correlate with disease activity and severity. This suggests an important role of IL-9 in the pathogenesis of SLE.

Four systems involved with congenital abnormalities: a new type of syndromic hearing loss - ADOC Wang's syndrome?

Syndromic hearing impairment encompasses hundreds of phenotypes. We identified a young female patient affected by the unique combination of dysplasia of the auricular system, patent ductus arteriosus (PDA), choroideremia, and enamel hypoplasia. The patient was treated with PDA ligature and left exploratory tympanotomy. Impairment in all four systems suggests a correlation with the neural crest. It is presumed that all of the features result from the same origin, probably through autosomal recessive inheritance or a novel mutation during the embryonic period. When audio-dento-oculo-cardio systems are involved, we suggest that this new syndrome can be named 'ADOC Wang's syndrome', summarizing the disorders of the four systems and indicative of the founding person (Dr Wang, the first and corresponding author of the paper).

Chronic Tinnitus following Electroconvulsive Therapy.

A 43-year-old female with a 27-year history of obsessive-compulsive disorder and major depression had previously been treated with psychotherapy, antidepressant, and antipsychotic medications. Because these treatments were minimally effective and because the frequency and duration of her depressive episodes continued to increase, the patient was scheduled to undergo a series of electroconvulsive therapy (ECT) procedures. The patient received four ECT treatments during one month. Stimulating current was delivered to the right frontotemporal region of the head. Electroencephalographic seizures occurred during each of the ECT procedures. After the patient recovered from anesthesia, she complained of headaches, muscle pain, amnesia, and, after the fourth ECT, she reported a ringing sound in her right ear. Audiometric testing the day after the fourth ECT revealed a slight increase in threshold for 8000 Hz tones in her right ear. It is likely that current delivered during the fourth ECT treatment triggered the perception of tinnitus for this patient. The unique organization of this patient's central nervous and auditory systems combined with her particular pharmacological history might have predisposed her to developing tinnitus.

Renal replacement therapy for prevention of contrast-induced acute kidney injury: a meta-analysis of randomized controlled trials.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is an important cause of acute renal injury. Several clinical trials using renal replacement therapy (RRT) for prevention of CI-AKI yielded conflicting results. We performed a meta-analysis to assess the efficacy of prophylactic RRT on CI-AKI. METHODS: Randomized controlled trials on CI-AKI using RRT were identified without language restriction in Cochrane library, Pubmed and Embase. Data extracted from literature were analyzed with Review manager and Stata software. RESULTS: Nine randomized controlled trials involving 751 patients were included. Heterogeneity was found across trials (p < 0.00001). A random effect model was used to combine the data. RRT reduced the risk of CI-AKI by 26% compared with the control group, but statistical significance was not reached (risk ratio (RR) 0.74, 95% CI 0.35-1.60, p = 0.45). Subgroup analysis of modality indicated that hemodialysis was ineffective in reducing the risk of CI-AKI (RR 1.21, 95% CI 0.63-2.32, p = 0.57), while CRRT decreased the incidence of CI-AKI (RR 0.22, 95% CI 0.07-0.64, p = 0.006). Subgroup analysis according to the CKD stage did not record heterogeneity across trials. RRT increased the odds of CI-AKI in CKD stage 3 patients (RR 1.53, 95% CI 0.07-0.64, p = 0.01), but decreased the occurrence of CI-AKI in patients with CKD stage higher than 3 (RR 0.74, 95% CI 0.35-1.60, p = 0.45). The pooled RR of the need for permanent dialysis demonstrated an insignificant trend towards benefit in patients treated with RRT (RR 0.61, 95% CI 0.26-1.40, p = 0.24). RRT reduced in-hospital mortality compared with control group (RR 0.33, 95% CI 0.14-0.77, p = 0.01). CONCLUSION: RRT fails to reduce the incidence of CI-AKI in CKD stage 3 patients, but may be beneficial in patients with more advanced renal function. CRRT is more effective than hemodialysis for prevention of CI-AKI. RRT is effective in reducing the in-hospital mortality of CI-AKI patients.

Deep brain stimulation effects in patients with tinnitus.

OBJECTIVE: To report deep brain stimulation (DBS) effects in patients with tinnitus. STUDY DESIGN: Case series with chart review. SETTING: Tertiary medical center. SUBJECTS AND METHODS: Seven patients implanted with DBS systems for movement disorders who also reported having tinnitus were interviewed about their tinnitus conditions. Four were available for testing in a specialized tinnitus clinic with their DBS systems turned off or on. Testing included matching of self-rated and psychoacoustically measured tinnitus loudness to measure the impact of DBS on tinnitus. RESULTS: Three of the seven patients reported reduced tinnitus loudness when DBS was turned on. Of the four patients tested in the clinic, results indicated that DBS of the ventralis intermedius nucleus of the thalamus caused decreases in tinnitus loudness in two patients with relatively prolonged residual inhibition. CONCLUSION: These results suggest that DBS of nonauditory thalamus structures may provide tinnitus relief for some patients.