OLCAY JONES - Academia.edu (original) (raw)

Papers by OLCAY JONES

Background Children with complex medical issues experience barriers to the transition of care fro... more Background Children with complex medical issues experience barriers to the transition of care from pediatric to adult providers. We sought to identify these barriers by elucidating the experiences of patients with idiopathic inflammatory muscle disorders. Methods We collected anonymous survey data using an online website. Patients and their families were solicited from the US and Canada through established clinics for children with idiopathic inflammatory muscle diseases as well as with the aid of a nonprofit organization for the benefit of such individuals. The parents of 45 older children/young adults suffering from idiopathic inflammatory muscle diseases were surveyed. As a basis of comparison, we similarly collected data from the parents of 207 younger children with inflammatory muscle diseases. The survey assessed transition of care issues confronting families of children and young adults with chronic juvenile myositis. Results Regardless of age of the patient, respondents were unlikely to have a designated health care provider assigned to aid in transition of care and were unlikely to be aware of a posted policy concerning transition of care at their pediatrician\u27s office. Additionally, regardless of age, patients and their families were unlikely to have a written plan for moving to adult care. Conclusions We identified deficiencies in the health care experiences of families as pertain to knowledge, self-advocacy, policy, and vocational readiness. Moreover, as children with complex medical issues grow up, parents attribute less self-advocacy to their children\u27s level of independence

PubMed, 1990

1. Prog Clin Biol Res. 1990;325:165-72. Effects in vitro of ethanol and acetaldehyde on natural k... more 1. Prog Clin Biol Res. 1990;325:165-72. Effects in vitro of ethanol and acetaldehyde on natural killer activity from rats. Yeralan O, Jones JM. Department of Microbiology/Immunology, University of Arkansas for Medical Sciences, Little Rock 72205. ...

Toxicology Letters, Jul 1, 1990

Rats were treated with LiCl or RbCl in drinking water for 65 days. Spleen cells from both treated... more Rats were treated with LiCl or RbCl in drinking water for 65 days. Spleen cells from both treated groups exhibited significantly greater proliferative responses to lipopolysaccharide (LPS) than those from untreated controls. Responses to concanavalin A (Con A) were not affected. Cytotoxic activities of natural killer (NK) cells from both treated groups were significantly less than those from untreated controls. In vitro, Li augmented responses of spleen cells to LPS, but the same doses of Rb suppressed the responses. Effects on responses to Con A were variable. Both Li and Rb alone had a small mitogenic effect on spleen cells.

Journal of Neurochemistry, Nov 23, 2002

Neuritic sprouting and disturbances of calcium homeostasis are well described in epilepsy. S100β ... more Neuritic sprouting and disturbances of calcium homeostasis are well described in epilepsy. S100β is an astrocyte-derived cytokine that promotes neurite growth and induces increases in levels of intracellular calcium in neurons. In sections of neocortex of surgically resected temporal lobe tissue from patients with intractable epilepsy, we found that the number of S100β-immunoreactive astrocytes was approximately threefold higher than that found in control patients (p < 0.001). These astrocytes were activated, i.e., enlarged, and had prominent processes. Temporal lobe tissue levels of S100β were shown by ELISA to be fivefold higher in 21 epileptics than in 12 controls (p < 0.001). The expression of the astrocyte intermediate filament protein, glial fibrillary acidic protein, was not significantly elevated in epileptics, suggesting a selective up-regulation of S100β expression. Our findings, together with established functions of S100β, suggest that this neurotrophic cytokine may be involved in the pathophysiology of epilepsy.

Methods in Neurosciences, 1993

Publisher Summary Cytokines—soluble factors of an information network—are produced by certain cel... more Publisher Summary Cytokines—soluble factors of an information network—are produced by certain cell types and induce specific functions in responder or target cells. Two brain-derived factors, interleukin 1 (IL-1) and S100, are considered as early contributors to a cascade of neurodegenerative events that lead to the neuropathophysiological changes that characterize Alzheimer's disease (AD), Down syndrome, and AIDS. This chapter provides an overview of the methods used to study the cellular expression of S100 and IL-1 in samples of temporal lobe of brain from individuals with those neurodegenerative diseases. It describes many functions of IL-1: namely, the macrophage-derived posttranslationally unmodified intracellular α isoform, and the initiation of number of cell-mediated immune responses by cleaved α and β isoforms of IL-1. The chapter also discusses methods to measure the levels and activities of S100 and IL-1 in human brain in health and disease. Prominent proliferation and morphogenesis of astrocytes, overgrowth of neuronal processes, paired helical filaments in neurons, and calcium-induced neuronal cell death are neuropathological changes characteristic of neurodegeneration.

Archives of pediatrics & adolescent medicine, Aug 1, 1983

Various defects in leukocyte function have been reported in Chédiak-Higashi syndrome (CHS); howev... more Various defects in leukocyte function have been reported in Chédiak-Higashi syndrome (CHS); however, to our knowledge, lymphocyte locomotor capacity has not been investigated. A 7-year-old boy with typical signs and symptoms of CHS showed impaired neutrophil, monocyte, and lymphocyte locomotion. Chemotaxis studies were performed by the micropore filter technique using modified Boyden chambers, and migration was measured by the leading front method. Treatment with ascorbic acid (vitamin C), 500 mg/day for five days, resulted in a significant increase in in vitro neutrophil and monocyte chemotaxis but failed to affect lymphocyte locomotion.

Arthritis and Rheumatism 40(9 Suppl. ), Apr 28, 1997

Methods in Neurosciences, 1993

Publisher Summary Cytokines—soluble factors of an information network—are produced by certain cel... more Publisher Summary Cytokines—soluble factors of an information network—are produced by certain cell types and induce specific functions in responder or target cells. Two brain-derived factors, interleukin 1 (IL-1) and S100, are considered as early contributors to a cascade of neurodegenerative events that lead to the neuropathophysiological changes that characterize Alzheimer's disease (AD), Down syndrome, and AIDS. This chapter provides an overview of the methods used to study the cellular expression of S100 and IL-1 in samples of temporal lobe of brain from individuals with those neurodegenerative diseases. It describes many functions of IL-1: namely, the macrophage-derived posttranslationally unmodified intracellular α isoform, and the initiation of number of cell-mediated immune responses by cleaved α and β isoforms of IL-1. The chapter also discusses methods to measure the levels and activities of S100 and IL-1 in human brain in health and disease. Prominent proliferation and morphogenesis of astrocytes, overgrowth of neuronal processes, paired helical filaments in neurons, and calcium-induced neuronal cell death are neuropathological changes characteristic of neurodegeneration.

Methods in Neurosciences, 1993

Toxicology Letters, 1990

Rats were treated with LiCl or RbCl in drinking water for 65 days. Spleen cells from both treated... more Rats were treated with LiCl or RbCl in drinking water for 65 days. Spleen cells from both treated groups exhibited significantly greater proliferative responses to lipopolysaccharide (LPS) than those from untreated controls. Responses to concanavalin A (Con A) were not affected. Cytotoxic activities of natural killer (NK) cells from both treated groups were significantly less than those from untreated controls. In vitro, Li augmented responses of spleen cells to LPS, but the same doses of Rb suppressed the responses. Effects on responses to Con A were variable. Both Li and Rb alone had a small mitogenic effect on spleen cells.

Alcoholism: Clinical and Experimental Research, 1991

The possible influences of ethanol and its metabolic product acetate on the surface expression of... more The possible influences of ethanol and its metabolic product acetate on the surface expression of HLA class I and class II antigens and CD 16 Fc receptors were examined. Fluorescent‐labeled monoclonal antibodies and flow cytometry were used to measure these antigens on leukocytes from reference controls, subjects admitted for alcohol detoxification, uremic patients undergoing hemodialysis using Cuprophan dialyzers and fluids containing 4 to 37 mm acetate, and uremic patients that were not hemodialyzed. In comparison to the controls, the mean intensity of staining for class I antigens was not changed significantly on lymphocytes or monocytes from alcoholics but was depressed on cells from eight of 12 uremic patients. Interferon‐γ above 5 units/ml was detected in less than 15% of plasma samples from controls, uremic patients or alcoholics on admission but was detected in four of eight samples from alcoholics at discharge (2‐4 days after admission). The intensity of staining for class ...

Arthritis & rheumatology, Jun 7, 2023

ObjectiveThis open‐label, 24‐week study was conducted to evaluate the safety and efficacy of abat... more ObjectiveThis open‐label, 24‐week study was conducted to evaluate the safety and efficacy of abatacept in patients with refractory juvenile dermatomyositis (DM).MethodsTen patients ≥7 years of age with moderate disease activity were enrolled in a 24‐week study to examine the safety of subcutaneous abatacept and patient responses to the treatment. The primary endpoint was the International Myositis Assessment and Clinical Studies (IMACS) group Definition Of Improvement (DOI). Secondary endpoints included safety, changes in the core set activity measures (CSMs) of the IMACS group and the Pediatric Rheumatology International Trials Organization, and improvements in disease activity based on the American College of Rheumatology (ACR)/EULAR response criteria for juvenile DM. Radiologists blinded with regard to participant data assessed magnetic resonance images (MRIs) of patient thigh muscles. Interferon (IFN)–regulated gene score was performed on whole‐blood RNA samples using a NanoString assay, and cytokines were assessed using a Luminex assay.ResultsFive patients achieved DOI at week 12, and 9 patients achieved DOI at week 24, including 2 patients with minimal, 4 patients with moderate, and 3 patients with major improvement by the 2016 ACR/EULAR response criteria for juvenile DM when patients were assessed using the CSMs of the IMACS Group. Improvements from baseline were seen in all CSMs at weeks 12 and 24, except in muscle enzymes. Daily glucocorticoid doses decreased from a mean of 16.7 mg at baseline to 10.2 mg at week 24 (P = 0.002). Average MRI muscle edema scores decreased from a mean baseline score of 5.3 to 2.3 at week 24 (P = 0.01). Six patients had down‐trending IFN‐regulated gene scores and galectin‐9 expression at week 24. Decreases in IFN‐regulated gene scores and in levels of interferon‐γ‐inducible protein 10kDa, galectin‐9, and interleukin‐2 correlated with improvements in disease activity and in muscle edema shown on MRI. Eleven grade 2 or 3 treatment‐emergent adverse events were observed.ConclusionThis open‐label study demonstrated that abatacept may be beneficial for patients with treatment‐refractory juvenile DM.image

Journal of clinical nephrology, Dec 9, 2019

Infantile cystinosis is a lysosomal storage disease leading to end stage kidney disease at early ... more Infantile cystinosis is a lysosomal storage disease leading to end stage kidney disease at early ages. There is no effective treatment and patients require long term dialysis or kidney transplant for survival. We present our experience on three affected children who received HLA matched allogeneic stem cell transplant. The protocol used was novel and designed to promote engraftment. The primary endpoint was safety for treatment related mortality or morbidity; All three children survived without serious adverse effects during extended follow up for over 4 years. Although we could not prove engraftment, all three children met secondary end point of sustained target functions over a 6 month follow-up. Further studies are warranted to further evaluate safety and effi cacy of MSC treatment for infantile cystinosis.

Annals of the Rheumatic Diseases

BackgroundThe interleukin-1 (IL-1) mediated systemic autoinflammatory diseases, including the cry... more BackgroundThe interleukin-1 (IL-1) mediated systemic autoinflammatory diseases, including the cryopyrin-associated periodic syndromes (CAPS), tumour necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD) and deficiency of the IL-1 receptor antagonist (DIRA), belong to a group of rare immunodysregulatory diseases that primarily present in early childhood with variable multiorgan involvement. When untreated, patients with severe clinical phenotypes have a poor prognosis, and diagnosis and management of these patients can be challenging. However, approved treatments targeting the proinflammatory cytokine IL-1 have been life changing and have significantly improved patient outcomes.ObjectiveTo establish evidence-based recommendations for diagnosis, treatment and monitoring of patients with IL-1 mediated autoinflammatory diseases to standardise their management.MethodsA multinational, multidisciplinary task force consisting of physician experts,...

Annals of the Rheumatic Diseases, 2020

Ultra-rare genetically defined IL-1 mediated autoinflammatory diseases (AIDs) include mevalonate ... more Ultra-rare genetically defined IL-1 mediated autoinflammatory diseases (AIDs) include mevalonate kinase deficiency (MKD), tumor necrosis factor receptor associated periodic syndrome (TRAPS), cryopyrinopathies (CAPS) and deficiency of the IL-1 receptor antagonist (DIRA). These disorders start perinatally, the clinical disease manifestations include systemic inflammation; and late diagnosis and inappropriate treatment cause irreversible organ damage. The varying skills of treating rheumatologists and paediatricians illustrate the need for management guidance, however criteria for validated methodology is geared towards common diseases with more heterogeneous pathogenesis.The focus of this systematic review includes the evaluation of the existing literature and the evaluation of existing EULAR methodology for use in the ultra-rare diseases with defined pathomechanisms, CAPS, TRAPS, MKD and DIRAEULAR standardized operating procedures were followed during the review, including a meeting ...

Pediatric ENT Infections, 2021

Proceedings of the National Academy of Sciences, 2020

Significance In this report we identify genetic susceptibility variants for periodic fever, aphth... more Significance In this report we identify genetic susceptibility variants for periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, the most common periodic fever syndrome in children. PFAPA shares risk loci at IL12A , STAT4, IL10 , and CCR1-CCR3 with Behçet’s disease and recurrent aphthous stomatitis, defining a family of Behçet’s spectrum disorders. Differential HLA associations along this spectrum may determine where individual phenotypes fall among the Behçet’s spectrum disorders.

RMD Open, 2020

ObjectivesLong-term safety and efficacy of adalimumab among patients with juvenile idiopathic art... more ObjectivesLong-term safety and efficacy of adalimumab among patients with juvenile idiopathic arthritis (JIA) was evaluated through 6 years of treatment.MethodsChildren aged 4–17 years with polyarticular JIA were enrolled in a phase III, randomised-withdrawal, double-blind, placebo-controlled trial consisting of a 16-week open-label lead-in period, 32-week randomised double-blind period and 360-week long-term extension. Patients were stratified by baseline methotrexate use. Adverse events (AEs) were monitored, and efficacy assessments included JIA American College of Rheumatology (JIA ACR) 30%, 50%, 70% or 90% responses and the proportions of patients achieving 27-joint Juvenile Arthritis Disease Activity Score (JADAS27) low disease activity (LDA, ≤3.8) and inactive disease (ID, ≤1).ResultsOf 171 patients enrolled, 62 (36%) completed the long-term extension. Twelve serious infections in 11 patients were reported through 592.8 patient-years of exposure. No cases of congestive heart f...

Annals of Hematology, Apr 17, 2023

Background Children with complex medical issues experience barriers to the transition of care fro... more Background Children with complex medical issues experience barriers to the transition of care from pediatric to adult providers. We sought to identify these barriers by elucidating the experiences of patients with idiopathic inflammatory muscle disorders. Methods We collected anonymous survey data using an online website. Patients and their families were solicited from the US and Canada through established clinics for children with idiopathic inflammatory muscle diseases as well as with the aid of a nonprofit organization for the benefit of such individuals. The parents of 45 older children/young adults suffering from idiopathic inflammatory muscle diseases were surveyed. As a basis of comparison, we similarly collected data from the parents of 207 younger children with inflammatory muscle diseases. The survey assessed transition of care issues confronting families of children and young adults with chronic juvenile myositis. Results Regardless of age of the patient, respondents were unlikely to have a designated health care provider assigned to aid in transition of care and were unlikely to be aware of a posted policy concerning transition of care at their pediatrician\u27s office. Additionally, regardless of age, patients and their families were unlikely to have a written plan for moving to adult care. Conclusions We identified deficiencies in the health care experiences of families as pertain to knowledge, self-advocacy, policy, and vocational readiness. Moreover, as children with complex medical issues grow up, parents attribute less self-advocacy to their children\u27s level of independence

PubMed, 1990

1. Prog Clin Biol Res. 1990;325:165-72. Effects in vitro of ethanol and acetaldehyde on natural k... more 1. Prog Clin Biol Res. 1990;325:165-72. Effects in vitro of ethanol and acetaldehyde on natural killer activity from rats. Yeralan O, Jones JM. Department of Microbiology/Immunology, University of Arkansas for Medical Sciences, Little Rock 72205. ...

Toxicology Letters, Jul 1, 1990

Rats were treated with LiCl or RbCl in drinking water for 65 days. Spleen cells from both treated... more Rats were treated with LiCl or RbCl in drinking water for 65 days. Spleen cells from both treated groups exhibited significantly greater proliferative responses to lipopolysaccharide (LPS) than those from untreated controls. Responses to concanavalin A (Con A) were not affected. Cytotoxic activities of natural killer (NK) cells from both treated groups were significantly less than those from untreated controls. In vitro, Li augmented responses of spleen cells to LPS, but the same doses of Rb suppressed the responses. Effects on responses to Con A were variable. Both Li and Rb alone had a small mitogenic effect on spleen cells.

Journal of Neurochemistry, Nov 23, 2002

Neuritic sprouting and disturbances of calcium homeostasis are well described in epilepsy. S100β ... more Neuritic sprouting and disturbances of calcium homeostasis are well described in epilepsy. S100β is an astrocyte-derived cytokine that promotes neurite growth and induces increases in levels of intracellular calcium in neurons. In sections of neocortex of surgically resected temporal lobe tissue from patients with intractable epilepsy, we found that the number of S100β-immunoreactive astrocytes was approximately threefold higher than that found in control patients (p < 0.001). These astrocytes were activated, i.e., enlarged, and had prominent processes. Temporal lobe tissue levels of S100β were shown by ELISA to be fivefold higher in 21 epileptics than in 12 controls (p < 0.001). The expression of the astrocyte intermediate filament protein, glial fibrillary acidic protein, was not significantly elevated in epileptics, suggesting a selective up-regulation of S100β expression. Our findings, together with established functions of S100β, suggest that this neurotrophic cytokine may be involved in the pathophysiology of epilepsy.

Methods in Neurosciences, 1993

Publisher Summary Cytokines—soluble factors of an information network—are produced by certain cel... more Publisher Summary Cytokines—soluble factors of an information network—are produced by certain cell types and induce specific functions in responder or target cells. Two brain-derived factors, interleukin 1 (IL-1) and S100, are considered as early contributors to a cascade of neurodegenerative events that lead to the neuropathophysiological changes that characterize Alzheimer's disease (AD), Down syndrome, and AIDS. This chapter provides an overview of the methods used to study the cellular expression of S100 and IL-1 in samples of temporal lobe of brain from individuals with those neurodegenerative diseases. It describes many functions of IL-1: namely, the macrophage-derived posttranslationally unmodified intracellular α isoform, and the initiation of number of cell-mediated immune responses by cleaved α and β isoforms of IL-1. The chapter also discusses methods to measure the levels and activities of S100 and IL-1 in human brain in health and disease. Prominent proliferation and morphogenesis of astrocytes, overgrowth of neuronal processes, paired helical filaments in neurons, and calcium-induced neuronal cell death are neuropathological changes characteristic of neurodegeneration.

Archives of pediatrics & adolescent medicine, Aug 1, 1983

Various defects in leukocyte function have been reported in Chédiak-Higashi syndrome (CHS); howev... more Various defects in leukocyte function have been reported in Chédiak-Higashi syndrome (CHS); however, to our knowledge, lymphocyte locomotor capacity has not been investigated. A 7-year-old boy with typical signs and symptoms of CHS showed impaired neutrophil, monocyte, and lymphocyte locomotion. Chemotaxis studies were performed by the micropore filter technique using modified Boyden chambers, and migration was measured by the leading front method. Treatment with ascorbic acid (vitamin C), 500 mg/day for five days, resulted in a significant increase in in vitro neutrophil and monocyte chemotaxis but failed to affect lymphocyte locomotion.

Arthritis and Rheumatism 40(9 Suppl. ), Apr 28, 1997

Methods in Neurosciences, 1993

Publisher Summary Cytokines—soluble factors of an information network—are produced by certain cel... more Publisher Summary Cytokines—soluble factors of an information network—are produced by certain cell types and induce specific functions in responder or target cells. Two brain-derived factors, interleukin 1 (IL-1) and S100, are considered as early contributors to a cascade of neurodegenerative events that lead to the neuropathophysiological changes that characterize Alzheimer's disease (AD), Down syndrome, and AIDS. This chapter provides an overview of the methods used to study the cellular expression of S100 and IL-1 in samples of temporal lobe of brain from individuals with those neurodegenerative diseases. It describes many functions of IL-1: namely, the macrophage-derived posttranslationally unmodified intracellular α isoform, and the initiation of number of cell-mediated immune responses by cleaved α and β isoforms of IL-1. The chapter also discusses methods to measure the levels and activities of S100 and IL-1 in human brain in health and disease. Prominent proliferation and morphogenesis of astrocytes, overgrowth of neuronal processes, paired helical filaments in neurons, and calcium-induced neuronal cell death are neuropathological changes characteristic of neurodegeneration.

Methods in Neurosciences, 1993

Toxicology Letters, 1990

Rats were treated with LiCl or RbCl in drinking water for 65 days. Spleen cells from both treated... more Rats were treated with LiCl or RbCl in drinking water for 65 days. Spleen cells from both treated groups exhibited significantly greater proliferative responses to lipopolysaccharide (LPS) than those from untreated controls. Responses to concanavalin A (Con A) were not affected. Cytotoxic activities of natural killer (NK) cells from both treated groups were significantly less than those from untreated controls. In vitro, Li augmented responses of spleen cells to LPS, but the same doses of Rb suppressed the responses. Effects on responses to Con A were variable. Both Li and Rb alone had a small mitogenic effect on spleen cells.

Alcoholism: Clinical and Experimental Research, 1991

The possible influences of ethanol and its metabolic product acetate on the surface expression of... more The possible influences of ethanol and its metabolic product acetate on the surface expression of HLA class I and class II antigens and CD 16 Fc receptors were examined. Fluorescent‐labeled monoclonal antibodies and flow cytometry were used to measure these antigens on leukocytes from reference controls, subjects admitted for alcohol detoxification, uremic patients undergoing hemodialysis using Cuprophan dialyzers and fluids containing 4 to 37 mm acetate, and uremic patients that were not hemodialyzed. In comparison to the controls, the mean intensity of staining for class I antigens was not changed significantly on lymphocytes or monocytes from alcoholics but was depressed on cells from eight of 12 uremic patients. Interferon‐γ above 5 units/ml was detected in less than 15% of plasma samples from controls, uremic patients or alcoholics on admission but was detected in four of eight samples from alcoholics at discharge (2‐4 days after admission). The intensity of staining for class ...

Arthritis & rheumatology, Jun 7, 2023

ObjectiveThis open‐label, 24‐week study was conducted to evaluate the safety and efficacy of abat... more ObjectiveThis open‐label, 24‐week study was conducted to evaluate the safety and efficacy of abatacept in patients with refractory juvenile dermatomyositis (DM).MethodsTen patients ≥7 years of age with moderate disease activity were enrolled in a 24‐week study to examine the safety of subcutaneous abatacept and patient responses to the treatment. The primary endpoint was the International Myositis Assessment and Clinical Studies (IMACS) group Definition Of Improvement (DOI). Secondary endpoints included safety, changes in the core set activity measures (CSMs) of the IMACS group and the Pediatric Rheumatology International Trials Organization, and improvements in disease activity based on the American College of Rheumatology (ACR)/EULAR response criteria for juvenile DM. Radiologists blinded with regard to participant data assessed magnetic resonance images (MRIs) of patient thigh muscles. Interferon (IFN)–regulated gene score was performed on whole‐blood RNA samples using a NanoString assay, and cytokines were assessed using a Luminex assay.ResultsFive patients achieved DOI at week 12, and 9 patients achieved DOI at week 24, including 2 patients with minimal, 4 patients with moderate, and 3 patients with major improvement by the 2016 ACR/EULAR response criteria for juvenile DM when patients were assessed using the CSMs of the IMACS Group. Improvements from baseline were seen in all CSMs at weeks 12 and 24, except in muscle enzymes. Daily glucocorticoid doses decreased from a mean of 16.7 mg at baseline to 10.2 mg at week 24 (P = 0.002). Average MRI muscle edema scores decreased from a mean baseline score of 5.3 to 2.3 at week 24 (P = 0.01). Six patients had down‐trending IFN‐regulated gene scores and galectin‐9 expression at week 24. Decreases in IFN‐regulated gene scores and in levels of interferon‐γ‐inducible protein 10kDa, galectin‐9, and interleukin‐2 correlated with improvements in disease activity and in muscle edema shown on MRI. Eleven grade 2 or 3 treatment‐emergent adverse events were observed.ConclusionThis open‐label study demonstrated that abatacept may be beneficial for patients with treatment‐refractory juvenile DM.image

Journal of clinical nephrology, Dec 9, 2019

Infantile cystinosis is a lysosomal storage disease leading to end stage kidney disease at early ... more Infantile cystinosis is a lysosomal storage disease leading to end stage kidney disease at early ages. There is no effective treatment and patients require long term dialysis or kidney transplant for survival. We present our experience on three affected children who received HLA matched allogeneic stem cell transplant. The protocol used was novel and designed to promote engraftment. The primary endpoint was safety for treatment related mortality or morbidity; All three children survived without serious adverse effects during extended follow up for over 4 years. Although we could not prove engraftment, all three children met secondary end point of sustained target functions over a 6 month follow-up. Further studies are warranted to further evaluate safety and effi cacy of MSC treatment for infantile cystinosis.

Annals of the Rheumatic Diseases

BackgroundThe interleukin-1 (IL-1) mediated systemic autoinflammatory diseases, including the cry... more BackgroundThe interleukin-1 (IL-1) mediated systemic autoinflammatory diseases, including the cryopyrin-associated periodic syndromes (CAPS), tumour necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD) and deficiency of the IL-1 receptor antagonist (DIRA), belong to a group of rare immunodysregulatory diseases that primarily present in early childhood with variable multiorgan involvement. When untreated, patients with severe clinical phenotypes have a poor prognosis, and diagnosis and management of these patients can be challenging. However, approved treatments targeting the proinflammatory cytokine IL-1 have been life changing and have significantly improved patient outcomes.ObjectiveTo establish evidence-based recommendations for diagnosis, treatment and monitoring of patients with IL-1 mediated autoinflammatory diseases to standardise their management.MethodsA multinational, multidisciplinary task force consisting of physician experts,...

Annals of the Rheumatic Diseases, 2020

Ultra-rare genetically defined IL-1 mediated autoinflammatory diseases (AIDs) include mevalonate ... more Ultra-rare genetically defined IL-1 mediated autoinflammatory diseases (AIDs) include mevalonate kinase deficiency (MKD), tumor necrosis factor receptor associated periodic syndrome (TRAPS), cryopyrinopathies (CAPS) and deficiency of the IL-1 receptor antagonist (DIRA). These disorders start perinatally, the clinical disease manifestations include systemic inflammation; and late diagnosis and inappropriate treatment cause irreversible organ damage. The varying skills of treating rheumatologists and paediatricians illustrate the need for management guidance, however criteria for validated methodology is geared towards common diseases with more heterogeneous pathogenesis.The focus of this systematic review includes the evaluation of the existing literature and the evaluation of existing EULAR methodology for use in the ultra-rare diseases with defined pathomechanisms, CAPS, TRAPS, MKD and DIRAEULAR standardized operating procedures were followed during the review, including a meeting ...

Pediatric ENT Infections, 2021

Proceedings of the National Academy of Sciences, 2020

Significance In this report we identify genetic susceptibility variants for periodic fever, aphth... more Significance In this report we identify genetic susceptibility variants for periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, the most common periodic fever syndrome in children. PFAPA shares risk loci at IL12A , STAT4, IL10 , and CCR1-CCR3 with Behçet’s disease and recurrent aphthous stomatitis, defining a family of Behçet’s spectrum disorders. Differential HLA associations along this spectrum may determine where individual phenotypes fall among the Behçet’s spectrum disorders.

RMD Open, 2020

ObjectivesLong-term safety and efficacy of adalimumab among patients with juvenile idiopathic art... more ObjectivesLong-term safety and efficacy of adalimumab among patients with juvenile idiopathic arthritis (JIA) was evaluated through 6 years of treatment.MethodsChildren aged 4–17 years with polyarticular JIA were enrolled in a phase III, randomised-withdrawal, double-blind, placebo-controlled trial consisting of a 16-week open-label lead-in period, 32-week randomised double-blind period and 360-week long-term extension. Patients were stratified by baseline methotrexate use. Adverse events (AEs) were monitored, and efficacy assessments included JIA American College of Rheumatology (JIA ACR) 30%, 50%, 70% or 90% responses and the proportions of patients achieving 27-joint Juvenile Arthritis Disease Activity Score (JADAS27) low disease activity (LDA, ≤3.8) and inactive disease (ID, ≤1).ResultsOf 171 patients enrolled, 62 (36%) completed the long-term extension. Twelve serious infections in 11 patients were reported through 592.8 patient-years of exposure. No cases of congestive heart f...

Annals of Hematology, Apr 17, 2023