The purpose of this work was to define the timing and magnitude of scleral contact lens settling,... more The purpose of this work was to define the timing and magnitude of scleral contact lens settling, the factors influencing settling, and to examine whether the amount of apical clearance has an impact on clinical performance or is associated with hypoxia-induced corneal changes. Eleven patients (22 eyes) with keratoconus were fitted with a mini-scleral lens (Esclera, Brazil). Three different lenses with successively greater sagittal depths were applied to achieve 3 levels of initial apical clearance: 100 to 200 μm (low), 200 to 300 μm (medium), and greater than 300 μm (high). Corneal apical clearance was measured at 15 min, 1, 2, 4, 6, and 8 hr with optical coherence tomography (OCT). Central corneal thickness was measured with OCT and Pentacam, in the morning and immediately after removal of the contact lens. Mean settling was 26.8±18.8 μm (42.7%) at 1 hr, 39.5±26.5 μm (62.9%) at 2 hr, 50.7±31.6 μm (80.8%) at 4 hr, 57.4±34.6 μm (91.4%) at 6 hr, and 62.8±38.4 μm (100%) at 8 hr. Settling rate was significantly lower in low apical clearance group (P=0.01). The smaller diameter lenses settled more (P=0.03). There was a slight statistically significant increase of 1.3% in central corneal thickness measured with OCT (P=0.03). Central corneal thickness measured with Pentacam at three locations increased slightly (P=0.001). Settling showed significant intrasubject and intersubject variations. The amount of corneal swelling and comfort scores did not differ significantly according to apical clearance. The average amount of settling was 62.8 μm after 8 hr, 80% of which occurred during the first 4 hr. Slight corneal swelling (1.3%) occurred after 8 hr of wear.
To investigate a certain set of methodological limitations in published anti-VEGF randomized cont... more To investigate a certain set of methodological limitations in published anti-VEGF randomized controlled trials (RCT). Descriptive methodological study METHODS: We did a PubMed search with the terms "bevacizumab OR ranibizumab OR pegaptanib OR aflibercept" and the limitations "humans" and "randomized controlled trials" in 15 of the highest impact factor general medicine and ophthalmology journals. We only included randomized controlled trials (RCTs) published as original articles, where an anti-vascular endothelial growth factor agent was used to treat eye disease. Two independent observers (OA, PK) read through each article and classified the articles according to a predefined set of criteria. The PubMed search yielded 209 articles, and 93 were classified as eligible. In most of the studies, the study drug was bevacizumab (52.6%, n=49), followed by ranibizumab (44.1%, n=41), pegaptanib (7.5%, n=7), and aflibercept (5.4%, n=5). Basic epidemiological data, including gender distribution (2.2%, n=2) and mean age (3.2%, n=3), were missing in 3.2% of the published RCTs. The power calculation for efficacy was mentioned in 48% (n=45) of the published work, and a power calculation for safety was considered in only one study (1.1%). Only 6 RCTs (6.5%) reported negative results. Power calculations for efficacy, an important component of an RCT, were missing in 51% of the RCTs we surveyed, while a power calculation for safety was only present in 1.1%. Around 60% of the published RCTs were labeled as an "efficacy and safety trial," while none of those studies had a power calculation for safety.
To present a rare case of bilateral peripapillary retinal leukemic infiltration associated with p... more To present a rare case of bilateral peripapillary retinal leukemic infiltration associated with papilledema without retrobulbar optic nerve involvement in a patient with acute lymphoblastic leukemia (ALL). This was a retrospective case report. A 24-year-old man with T-cell ALL and 2-month history of papilledema presented to our department with reduction of visual acuity in the left eye. Visual acuity was 20/60 in the right eye and hand movements in the left eye. Fundus examination revealed grade 3 papilledema, bilateral peripapillary leukemic infiltration, and intraretinal hemorrhages. Cranial magnetic resonance imaging did not show any sign of cranial mass or optic nerve involvement. Pulse steroid therapy and oral acetazolamide was started. At day 18, visual acuity improved to 20/40 in the right eye and 20/60 in the left eye, while papilledema improved to grade 1 and hemorrhages regressed. To our knowledge, there is no other report of peripapillary leukemic infiltration in the absence of retrobulbar optic nerve involvement. We suspect that papilledema might have facilitated peripapillary retinal infiltration due to altered vascular permeability. The reverse could also be possible: leukemic infiltration leading to increase in vascular permeability may also contribute to papilledema.
Most of the statistical tests used in significance testing are based on the assumption that each ... more Most of the statistical tests used in significance testing are based on the assumption that each data entry is independent from other entries, however, we observe that in many articles researchers include data from 2 eyes as independent variables while performing these statistical tests. The aim of this study was to formally survey the prevalence of the above-mentioned "double-organ bias" in randomized controlled trials (RCT) of glaucoma. We did a PubMed search with the terms "glaucoma" and limitations "Humans" and "Randomized Controlled Trials" in 15 highest-impact-factor ophthalmology journals between November 2002 and November 2012. We only included RCTs published as an original article, where the aim was treating glaucoma. Two independent observers (M.K. and A.S.E.) read through each article and classified the articles according to treatment modality (medical, laser, or surgical) and presence of double-organ bias. The PubMed search yielded 270 articles. A total of 130 articles qualified for the survey. Eighty-five of the RCTs were medical studies, 11 were laser studies, and 34 studies evaluated the outcome of a surgical procedure. In 17 of the 130 articles (13.1%), double-organ bias was found. Prevalence of the double-organ bias was not significantly different between medical (12.9%), laser (14.7%), and surgical (9.1%) studies. Double-organ bias was observed around 13.1% of the published RCTs, leading to inaccurate statistical testing.
ABSTRACT Background Guidelines on reporting randomized controlled trials advise against performin... more ABSTRACT Background Guidelines on reporting randomized controlled trials advise against performing baseline comparison in randomized groups (1). Such comparison is considered futile as any difference will be by chance by definition (2). In non-randomized studies, on the contrary, the baseline characteristics of the study groups should be compared because the differences may have direct implications on the results. Objectives The aim of this study was to determine the frequency of inappropriate commission or omission of baseline comparisons in randomized and non-randomized studies, respectively. Methods A PubMed search was conducted to identify clinical studies among humans, designed to test the effect of a treatment or an observation in more than one group in 3 major rheumatology journals; Annals of the Rheumatic Diseases, Arthritis and Rheumatism and Rheumatology (Oxford) from June 2010 to June 2011. Studies were grouped as either randomized or non-randomized. We evaluated each study as to how the baseline characteristics were presented. Also the frequencies of inappropriate commission or omission of statistical comparisons were tabulated. Results 205 studies were found, 107 were included. There were 60 randomized trials and 47 non-randomized studies. Among the randomized studies, 6/60 (10%) reported inappropriate baseline statistical comparisons. On the other hand among the non-randomized studies, 27/47 (57%) omitted baseline statistical comparison. In 10 of these 27 studies, there was no table presenting the characteristics of the groups subject to comparison. 17 studies on the other hand presented baseline groups in a table 1 but did no statistical comparisons although necessary. Conclusions The CONSORT statement seems to be better adhered to when reporting randomized controlled trials. On the other hand there is common and inappropriate omission of the necessary statistical comparisons at baseline in non-randomized studies. In this line there’s an obvious need to improve adherence to the TREND statement (3). Disclosure of Interest None Declared
ABSTRACT Background Takayasu's arteritis (TAK) is an inflammatory, granulomatous vasculit... more ABSTRACT Background Takayasu's arteritis (TAK) is an inflammatory, granulomatous vasculitis affecting aorta and its major branches. According to the type of vascular involvement, Takayasu's retinopathy (TR) and hypertensive retinopathy (HR) may be observed. Complications related to chronic immunosuppression and steroid therapy are also not infrequent in TAK and complications including amarosis fugax, iris neovascularization, glaucoma, cataract, uveitis and anterior ischemic optic neuropathy have been reported. Methods We screened 46 patients with TAK (43 female, 3 male, mean age 42.5±11.3 years, mean disease duration 5.7±5.1 years), followed at Marmara University Hospital Rheumatology clinics, for the presence of ocular complications. Forty patients were on low-dose (<10 mg/d prednisolone) corticosteroids, 25 were on azathioprine, 17 were on methotrexate and 2 patients were on leflunomide. Results None of the patients suffered from an ocular disease activity or complication causing permanent reduction in visual acuity. Eight patients (17%) had HR (grade 1-2) and only one patient (2%) had TR (grade 1). Seven patients (15%) had posterior subcapsular cataract, one patient (2%) was bilaterally pseudophacic and 37 (83%) had no steroid-related cataract. None of the patients had steroid-induced glaucoma or neovascular glaucoma. When comparing the patients with or without cataract, there were no statistically significant differences for the cumulative steroid dose (7608±5954mg vs. 8746±5497mg; p=0.46) or ITAS scores for disease activity (6.7±1.5 vs. 9.4±5.4; p=0.28). The patients with HR had a higher disease duration compared to the patients without HR (8.4±6.9 years vs. 4.0±2.6 years; p=0.02) Conclusions The prevalence of TR was reported to be higher (15% and 13.5%)1–2 in previous two similar decriptive studies, while prevalence of HR (16% and 30.8%)1–2 and steroid-related cataract (%23)1 was similar to our study. We did not observe any of the other above-mentioned serious complications reported in the previous studies. This is the first study to report a low prevalence of TR and related ischemic complications in TAK. This finding can be explained by: 1. our unselected study population from a rheumatology clinic, rather than an ophthalmology clinic (usually with a selection bias), 2. our study group having a milder eye disease due to a sufficient control of general disease activity, attenuating the severity of ocular disease or 3. a milder clinical course of TAK in Turkey. Further follow-up of our cohort will clarify our observations better. References Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2691
Acute ethanol intoxication has been shown to cause oxidative damage in many organ systems includi... more Acute ethanol intoxication has been shown to cause oxidative damage in many organ systems including the brain. Erythropoietin has antioxidant effects and prevents neuronal damage in the animal model of ischemic brain injury. In this study, we aimed to investigate the effects of darbepoetin alpha, an analog of erythropoietin with a longer half-life and higher in vivo activity, on ethanol-induced acute brain injury. Forty-eight Wistar albino rats were allocated to four groups. The first group received ethanol treatment (E), the second group was treated with ethanol and darbepoetin (ED), the third group received only saline treatment (S), and the fourth group received both saline and darbepoetin treatment (SD). Plasma S100-β and neuron-specific enolase (NSE) levels were measured. Histopathological evaluation of the brains was performed. The plasma S100-β and NSE levels were significantly lower in group ED compared with group E. In group E, we have observed focal red-neuron formation at...
data suggest that the use of disease control groups and proper use of power calculations were neg... more data suggest that the use of disease control groups and proper use of power calculations were neglected in published reports. We surveyed these and other methodological shortcomings in reports published within the last decade about one specific topic, Behcet's syndrome. We reason that recognizing such methodological shortcomings will lead to better quality clinical and basic science articles. articles published in the 15 highest impact factor journals on rheumatology, ophthalmology, dermatology, and general medicine between January 1999 and January 2009 were searched for original reports on Behcet's syndrome. Study designs (study types and time element), control groups, demographic data, use of power calculations, and reporting of negative results were specifically tabulated. most studies on Behcet's syndrome were cross-sectional (83%). Prospective longitudinal studies were few (7%). In a considerable proportion of papers (21%), some basic demographic data were missing. Power calculations were rare (3%) even in randomized controlled trials and were not considered at all in clinical hypothesis-testing. Disease control groups were present in slightly over half of clinical and laboratory original research, while just 13% of genetic association studies included disease controls. Only 12% of all reports concerned mainly negative outcomes. a considerable number of the published research articles have methodological weaknesses. The generalizability of what we observed in Behcet's syndrome to other research topics needs to be formally studied.
CD4(+)CD25(+) regulatory T cells (T regs) play a major role in the maintenance of self-tolerance ... more CD4(+)CD25(+) regulatory T cells (T regs) play a major role in the maintenance of self-tolerance and immune suppression, although the mechanisms controlling T reg development and suppressor function remain incompletely understood. Herein, we provide evidence that Kruppel-like factor 10 (KLF10/TIEG1) constitutes an important regulator of T regulatory cell suppressor function and CD4(+)CD25(-) T cell activation through distinct mechanisms involving transforming growth factor (TGF)-beta1 and Foxp3. KLF10 overexpressing CD4(+)CD25(-) T cells induced both TGF-beta1 and Foxp3 expression, an effect associated with reduced T-Bet (Th1 marker) and Gata3 (Th2 marker) mRNA expression. Consistently, KLF10(-/-) CD4(+)CD25(-) T cells have enhanced differentiation along both Th1 and Th2 pathways and elaborate higher levels of Th1 and Th2 cytokines. Furthermore, KLF10(-/-) CD4(+)CD25(-) T cell effectors cannot be appropriately suppressed by wild-type T regs. Surprisingly, KLF10(-/-) T reg cells have reduced suppressor function, independent of Foxp3 expression, with decreased expression and elaboration of TGF-beta1, an effect completely rescued by exogenous treatment with TGF-beta1. Mechanistic studies demonstrate that in response to TGF-beta1, KLF10 can transactivate both TGF-beta1 and Foxp3 promoters, implicating KLF10 in a positive feedback loop that may promote cell-intrinsic control of T cell activation. Finally, KLF10(-/-) CD4(+)CD25(-) T cells promoted atherosclerosis by approximately 2-fold in ApoE(-/-)/scid/scid mice with increased leukocyte accumulation and peripheral pro-inflammatory cytokines. Thus, KLF10 is a critical regulator in the transcriptional network controlling TGF-beta1 in both CD4(+)CD25(-) T cells and T regs and plays an important role in regulating atherosclerotic lesion formation in mice.
A 26-year-old female patient presented with redness, lid edema on the right eye and diplopia on l... more A 26-year-old female patient presented with redness, lid edema on the right eye and diplopia on left gaze. There was a minimal limitation of adduction of the right eye, accompanied with pain and diplopia. Orbital magnetic resonance imaging confirmed the diagnosis of orbital myositis. Anti-endomysial immunoglobulin (Ig) A, anti-endomysial IgG, anti-gliadin IgA and anti-tissue transglutaminase IgG antibodies were positive, while other tests for autoimmune diseases were unremarkable. The patient stated that her diarrhea had been relieved by a gluten-free diet. Methylprednisolone therapy (1 mg/kg) was started and on her next visit her complaints were relieved. Later, methotrexate (15 mg/week) was added to the therapy as the patient became steroid-dependent, and she has been attack-free for the last 3 months under methotrexate and low-dose methylprednisolone (4 mg/day) treatment. Associations between orbital myositis and various autoimmune diseases have previously been reported. We report here the first case of associated orbital myositis and celiac disease.
Clinical studies using bone marrow-derived proangiogenic cells (PACs) have demonstrated modest im... more Clinical studies using bone marrow-derived proangiogenic cells (PACs) have demonstrated modest improvements of function and/or perfusion of ischemic myocardium or skeletal muscle. Because the identities of these PACs and their functional ability to promote neovascularization remain poorly understood, it is possible that a subset of robust PACs exists but is obscured by the heterogeneous nature of this cell population. Herein, we found that common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs) preferentially differentiate into PACs compared with megakaryocyte-erythrocyte progenitors, hematopoietic stem cells, and common lymphoid progenitors. In vivo hindlimb ischemia studies and Matrigel plug assays verified the enhanced neovascularization properties uniquely associated with PACs derived from CMPs and GMPs. Taken together, these observations identify CMPs and GMPs as key bone marrow progenitors for optimal PAC function in vitro and in vivo and provide a foundation for novel therapeutic approaches to modulate angiogenesis.
The purpose of this work was to define the timing and magnitude of scleral contact lens settling,... more The purpose of this work was to define the timing and magnitude of scleral contact lens settling, the factors influencing settling, and to examine whether the amount of apical clearance has an impact on clinical performance or is associated with hypoxia-induced corneal changes. Eleven patients (22 eyes) with keratoconus were fitted with a mini-scleral lens (Esclera, Brazil). Three different lenses with successively greater sagittal depths were applied to achieve 3 levels of initial apical clearance: 100 to 200 μm (low), 200 to 300 μm (medium), and greater than 300 μm (high). Corneal apical clearance was measured at 15 min, 1, 2, 4, 6, and 8 hr with optical coherence tomography (OCT). Central corneal thickness was measured with OCT and Pentacam, in the morning and immediately after removal of the contact lens. Mean settling was 26.8±18.8 μm (42.7%) at 1 hr, 39.5±26.5 μm (62.9%) at 2 hr, 50.7±31.6 μm (80.8%) at 4 hr, 57.4±34.6 μm (91.4%) at 6 hr, and 62.8±38.4 μm (100%) at 8 hr. Settling rate was significantly lower in low apical clearance group (P=0.01). The smaller diameter lenses settled more (P=0.03). There was a slight statistically significant increase of 1.3% in central corneal thickness measured with OCT (P=0.03). Central corneal thickness measured with Pentacam at three locations increased slightly (P=0.001). Settling showed significant intrasubject and intersubject variations. The amount of corneal swelling and comfort scores did not differ significantly according to apical clearance. The average amount of settling was 62.8 μm after 8 hr, 80% of which occurred during the first 4 hr. Slight corneal swelling (1.3%) occurred after 8 hr of wear.
To investigate a certain set of methodological limitations in published anti-VEGF randomized cont... more To investigate a certain set of methodological limitations in published anti-VEGF randomized controlled trials (RCT). Descriptive methodological study METHODS: We did a PubMed search with the terms "bevacizumab OR ranibizumab OR pegaptanib OR aflibercept" and the limitations "humans" and "randomized controlled trials" in 15 of the highest impact factor general medicine and ophthalmology journals. We only included randomized controlled trials (RCTs) published as original articles, where an anti-vascular endothelial growth factor agent was used to treat eye disease. Two independent observers (OA, PK) read through each article and classified the articles according to a predefined set of criteria. The PubMed search yielded 209 articles, and 93 were classified as eligible. In most of the studies, the study drug was bevacizumab (52.6%, n=49), followed by ranibizumab (44.1%, n=41), pegaptanib (7.5%, n=7), and aflibercept (5.4%, n=5). Basic epidemiological data, including gender distribution (2.2%, n=2) and mean age (3.2%, n=3), were missing in 3.2% of the published RCTs. The power calculation for efficacy was mentioned in 48% (n=45) of the published work, and a power calculation for safety was considered in only one study (1.1%). Only 6 RCTs (6.5%) reported negative results. Power calculations for efficacy, an important component of an RCT, were missing in 51% of the RCTs we surveyed, while a power calculation for safety was only present in 1.1%. Around 60% of the published RCTs were labeled as an "efficacy and safety trial," while none of those studies had a power calculation for safety.
To present a rare case of bilateral peripapillary retinal leukemic infiltration associated with p... more To present a rare case of bilateral peripapillary retinal leukemic infiltration associated with papilledema without retrobulbar optic nerve involvement in a patient with acute lymphoblastic leukemia (ALL). This was a retrospective case report. A 24-year-old man with T-cell ALL and 2-month history of papilledema presented to our department with reduction of visual acuity in the left eye. Visual acuity was 20/60 in the right eye and hand movements in the left eye. Fundus examination revealed grade 3 papilledema, bilateral peripapillary leukemic infiltration, and intraretinal hemorrhages. Cranial magnetic resonance imaging did not show any sign of cranial mass or optic nerve involvement. Pulse steroid therapy and oral acetazolamide was started. At day 18, visual acuity improved to 20/40 in the right eye and 20/60 in the left eye, while papilledema improved to grade 1 and hemorrhages regressed. To our knowledge, there is no other report of peripapillary leukemic infiltration in the absence of retrobulbar optic nerve involvement. We suspect that papilledema might have facilitated peripapillary retinal infiltration due to altered vascular permeability. The reverse could also be possible: leukemic infiltration leading to increase in vascular permeability may also contribute to papilledema.
Most of the statistical tests used in significance testing are based on the assumption that each ... more Most of the statistical tests used in significance testing are based on the assumption that each data entry is independent from other entries, however, we observe that in many articles researchers include data from 2 eyes as independent variables while performing these statistical tests. The aim of this study was to formally survey the prevalence of the above-mentioned "double-organ bias" in randomized controlled trials (RCT) of glaucoma. We did a PubMed search with the terms "glaucoma" and limitations "Humans" and "Randomized Controlled Trials" in 15 highest-impact-factor ophthalmology journals between November 2002 and November 2012. We only included RCTs published as an original article, where the aim was treating glaucoma. Two independent observers (M.K. and A.S.E.) read through each article and classified the articles according to treatment modality (medical, laser, or surgical) and presence of double-organ bias. The PubMed search yielded 270 articles. A total of 130 articles qualified for the survey. Eighty-five of the RCTs were medical studies, 11 were laser studies, and 34 studies evaluated the outcome of a surgical procedure. In 17 of the 130 articles (13.1%), double-organ bias was found. Prevalence of the double-organ bias was not significantly different between medical (12.9%), laser (14.7%), and surgical (9.1%) studies. Double-organ bias was observed around 13.1% of the published RCTs, leading to inaccurate statistical testing.
ABSTRACT Background Guidelines on reporting randomized controlled trials advise against performin... more ABSTRACT Background Guidelines on reporting randomized controlled trials advise against performing baseline comparison in randomized groups (1). Such comparison is considered futile as any difference will be by chance by definition (2). In non-randomized studies, on the contrary, the baseline characteristics of the study groups should be compared because the differences may have direct implications on the results. Objectives The aim of this study was to determine the frequency of inappropriate commission or omission of baseline comparisons in randomized and non-randomized studies, respectively. Methods A PubMed search was conducted to identify clinical studies among humans, designed to test the effect of a treatment or an observation in more than one group in 3 major rheumatology journals; Annals of the Rheumatic Diseases, Arthritis and Rheumatism and Rheumatology (Oxford) from June 2010 to June 2011. Studies were grouped as either randomized or non-randomized. We evaluated each study as to how the baseline characteristics were presented. Also the frequencies of inappropriate commission or omission of statistical comparisons were tabulated. Results 205 studies were found, 107 were included. There were 60 randomized trials and 47 non-randomized studies. Among the randomized studies, 6/60 (10%) reported inappropriate baseline statistical comparisons. On the other hand among the non-randomized studies, 27/47 (57%) omitted baseline statistical comparison. In 10 of these 27 studies, there was no table presenting the characteristics of the groups subject to comparison. 17 studies on the other hand presented baseline groups in a table 1 but did no statistical comparisons although necessary. Conclusions The CONSORT statement seems to be better adhered to when reporting randomized controlled trials. On the other hand there is common and inappropriate omission of the necessary statistical comparisons at baseline in non-randomized studies. In this line there’s an obvious need to improve adherence to the TREND statement (3). Disclosure of Interest None Declared
ABSTRACT Background Takayasu's arteritis (TAK) is an inflammatory, granulomatous vasculit... more ABSTRACT Background Takayasu's arteritis (TAK) is an inflammatory, granulomatous vasculitis affecting aorta and its major branches. According to the type of vascular involvement, Takayasu's retinopathy (TR) and hypertensive retinopathy (HR) may be observed. Complications related to chronic immunosuppression and steroid therapy are also not infrequent in TAK and complications including amarosis fugax, iris neovascularization, glaucoma, cataract, uveitis and anterior ischemic optic neuropathy have been reported. Methods We screened 46 patients with TAK (43 female, 3 male, mean age 42.5±11.3 years, mean disease duration 5.7±5.1 years), followed at Marmara University Hospital Rheumatology clinics, for the presence of ocular complications. Forty patients were on low-dose (<10 mg/d prednisolone) corticosteroids, 25 were on azathioprine, 17 were on methotrexate and 2 patients were on leflunomide. Results None of the patients suffered from an ocular disease activity or complication causing permanent reduction in visual acuity. Eight patients (17%) had HR (grade 1-2) and only one patient (2%) had TR (grade 1). Seven patients (15%) had posterior subcapsular cataract, one patient (2%) was bilaterally pseudophacic and 37 (83%) had no steroid-related cataract. None of the patients had steroid-induced glaucoma or neovascular glaucoma. When comparing the patients with or without cataract, there were no statistically significant differences for the cumulative steroid dose (7608±5954mg vs. 8746±5497mg; p=0.46) or ITAS scores for disease activity (6.7±1.5 vs. 9.4±5.4; p=0.28). The patients with HR had a higher disease duration compared to the patients without HR (8.4±6.9 years vs. 4.0±2.6 years; p=0.02) Conclusions The prevalence of TR was reported to be higher (15% and 13.5%)1–2 in previous two similar decriptive studies, while prevalence of HR (16% and 30.8%)1–2 and steroid-related cataract (%23)1 was similar to our study. We did not observe any of the other above-mentioned serious complications reported in the previous studies. This is the first study to report a low prevalence of TR and related ischemic complications in TAK. This finding can be explained by: 1. our unselected study population from a rheumatology clinic, rather than an ophthalmology clinic (usually with a selection bias), 2. our study group having a milder eye disease due to a sufficient control of general disease activity, attenuating the severity of ocular disease or 3. a milder clinical course of TAK in Turkey. Further follow-up of our cohort will clarify our observations better. References Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2691
Acute ethanol intoxication has been shown to cause oxidative damage in many organ systems includi... more Acute ethanol intoxication has been shown to cause oxidative damage in many organ systems including the brain. Erythropoietin has antioxidant effects and prevents neuronal damage in the animal model of ischemic brain injury. In this study, we aimed to investigate the effects of darbepoetin alpha, an analog of erythropoietin with a longer half-life and higher in vivo activity, on ethanol-induced acute brain injury. Forty-eight Wistar albino rats were allocated to four groups. The first group received ethanol treatment (E), the second group was treated with ethanol and darbepoetin (ED), the third group received only saline treatment (S), and the fourth group received both saline and darbepoetin treatment (SD). Plasma S100-β and neuron-specific enolase (NSE) levels were measured. Histopathological evaluation of the brains was performed. The plasma S100-β and NSE levels were significantly lower in group ED compared with group E. In group E, we have observed focal red-neuron formation at...
data suggest that the use of disease control groups and proper use of power calculations were neg... more data suggest that the use of disease control groups and proper use of power calculations were neglected in published reports. We surveyed these and other methodological shortcomings in reports published within the last decade about one specific topic, Behcet's syndrome. We reason that recognizing such methodological shortcomings will lead to better quality clinical and basic science articles. articles published in the 15 highest impact factor journals on rheumatology, ophthalmology, dermatology, and general medicine between January 1999 and January 2009 were searched for original reports on Behcet's syndrome. Study designs (study types and time element), control groups, demographic data, use of power calculations, and reporting of negative results were specifically tabulated. most studies on Behcet's syndrome were cross-sectional (83%). Prospective longitudinal studies were few (7%). In a considerable proportion of papers (21%), some basic demographic data were missing. Power calculations were rare (3%) even in randomized controlled trials and were not considered at all in clinical hypothesis-testing. Disease control groups were present in slightly over half of clinical and laboratory original research, while just 13% of genetic association studies included disease controls. Only 12% of all reports concerned mainly negative outcomes. a considerable number of the published research articles have methodological weaknesses. The generalizability of what we observed in Behcet's syndrome to other research topics needs to be formally studied.
CD4(+)CD25(+) regulatory T cells (T regs) play a major role in the maintenance of self-tolerance ... more CD4(+)CD25(+) regulatory T cells (T regs) play a major role in the maintenance of self-tolerance and immune suppression, although the mechanisms controlling T reg development and suppressor function remain incompletely understood. Herein, we provide evidence that Kruppel-like factor 10 (KLF10/TIEG1) constitutes an important regulator of T regulatory cell suppressor function and CD4(+)CD25(-) T cell activation through distinct mechanisms involving transforming growth factor (TGF)-beta1 and Foxp3. KLF10 overexpressing CD4(+)CD25(-) T cells induced both TGF-beta1 and Foxp3 expression, an effect associated with reduced T-Bet (Th1 marker) and Gata3 (Th2 marker) mRNA expression. Consistently, KLF10(-/-) CD4(+)CD25(-) T cells have enhanced differentiation along both Th1 and Th2 pathways and elaborate higher levels of Th1 and Th2 cytokines. Furthermore, KLF10(-/-) CD4(+)CD25(-) T cell effectors cannot be appropriately suppressed by wild-type T regs. Surprisingly, KLF10(-/-) T reg cells have reduced suppressor function, independent of Foxp3 expression, with decreased expression and elaboration of TGF-beta1, an effect completely rescued by exogenous treatment with TGF-beta1. Mechanistic studies demonstrate that in response to TGF-beta1, KLF10 can transactivate both TGF-beta1 and Foxp3 promoters, implicating KLF10 in a positive feedback loop that may promote cell-intrinsic control of T cell activation. Finally, KLF10(-/-) CD4(+)CD25(-) T cells promoted atherosclerosis by approximately 2-fold in ApoE(-/-)/scid/scid mice with increased leukocyte accumulation and peripheral pro-inflammatory cytokines. Thus, KLF10 is a critical regulator in the transcriptional network controlling TGF-beta1 in both CD4(+)CD25(-) T cells and T regs and plays an important role in regulating atherosclerotic lesion formation in mice.
A 26-year-old female patient presented with redness, lid edema on the right eye and diplopia on l... more A 26-year-old female patient presented with redness, lid edema on the right eye and diplopia on left gaze. There was a minimal limitation of adduction of the right eye, accompanied with pain and diplopia. Orbital magnetic resonance imaging confirmed the diagnosis of orbital myositis. Anti-endomysial immunoglobulin (Ig) A, anti-endomysial IgG, anti-gliadin IgA and anti-tissue transglutaminase IgG antibodies were positive, while other tests for autoimmune diseases were unremarkable. The patient stated that her diarrhea had been relieved by a gluten-free diet. Methylprednisolone therapy (1 mg/kg) was started and on her next visit her complaints were relieved. Later, methotrexate (15 mg/week) was added to the therapy as the patient became steroid-dependent, and she has been attack-free for the last 3 months under methotrexate and low-dose methylprednisolone (4 mg/day) treatment. Associations between orbital myositis and various autoimmune diseases have previously been reported. We report here the first case of associated orbital myositis and celiac disease.
Clinical studies using bone marrow-derived proangiogenic cells (PACs) have demonstrated modest im... more Clinical studies using bone marrow-derived proangiogenic cells (PACs) have demonstrated modest improvements of function and/or perfusion of ischemic myocardium or skeletal muscle. Because the identities of these PACs and their functional ability to promote neovascularization remain poorly understood, it is possible that a subset of robust PACs exists but is obscured by the heterogeneous nature of this cell population. Herein, we found that common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs) preferentially differentiate into PACs compared with megakaryocyte-erythrocyte progenitors, hematopoietic stem cells, and common lymphoid progenitors. In vivo hindlimb ischemia studies and Matrigel plug assays verified the enhanced neovascularization properties uniquely associated with PACs derived from CMPs and GMPs. Taken together, these observations identify CMPs and GMPs as key bone marrow progenitors for optimal PAC function in vitro and in vivo and provide a foundation for novel therapeutic approaches to modulate angiogenesis.
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