61 research outputs found
Elicitation of expert prior opinion:application to the MYPAN trial in childhood polyarteritis nodosa
Objectives Definitive sample sizes for clinical trials in rare diseases are usually infeasible. Bayesian methodology can be used to maximise what is learnt from clinical trials in these circumstances. We elicited expert prior opinion for a future Bayesian randomised controlled trial for a rare inflammatory paediatric disease, polyarteritis nodosa (MYPAN, Mycophenolate mofetil for polyarteritis nodosa). Methods A Bayesian prior elicitation meeting was convened. Opinion was sought on the probability that a patient in the MYPAN trial treated with cyclophosphamide would achieve disease remission within 6-months, and on the relative efficacies of mycophenolate mofetil and cyclophosphamide. Expert opinion was combined with previously unseen data from a recently completed randomised controlled trial in ANCA associated vasculitis. Results A pan-European group of fifteen experts participated in the elicitation meeting. Consensus expert prior opinion was that the most likely rates of disease remission within 6 months on cyclophosphamide or mycophenolate mofetil were 74% and 71%, respectively. This prior opinion will now be taken forward and will be modified to formulate a Bayesian posterior opinion once the MYPAN trial data from 40 patients randomised 1:1 to either CYC or MMF become available. Conclusions We suggest that the methodological template we propose could be applied to trial design for other rare diseases
Elicitation of expert prior opinion: application to the MYPAN trial in childhood polyarteritis nodosa.
OBJECTIVES: Definitive sample sizes for clinical trials in rare diseases are usually infeasible. Bayesian methodology can be used to maximise what is learnt from clinical trials in these circumstances. We elicited expert prior opinion for a future Bayesian randomised controlled trial for a rare inflammatory paediatric disease, polyarteritis nodosa (MYPAN, Mycophenolate mofetil for polyarteritis nodosa). METHODS: A Bayesian prior elicitation meeting was convened. Opinion was sought on the probability that a patient in the MYPAN trial treated with cyclophosphamide would achieve disease remission within 6-months, and on the relative efficacies of mycophenolate mofetil and cyclophosphamide. Expert opinion was combined with previously unseen data from a recently completed randomised controlled trial in ANCA associated vasculitis. RESULTS: A pan-European group of fifteen experts participated in the elicitation meeting. Consensus expert prior opinion was that the most likely rates of disease remission within 6 months on cyclophosphamide or mycophenolate mofetil were 74% and 71%, respectively. This prior opinion will now be taken forward and will be modified to formulate a Bayesian posterior opinion once the MYPAN trial data from 40 patients randomised 1:1 to either CYC or MMF become available. CONCLUSIONS: We suggest that the methodological template we propose could be applied to trial design for other rare diseases
Deep white matter lesions with persistent diffusion restriction on MRI as a diagnostic clue: Neuroimaging of a turkish family with hereditary diffuse leukoencephalopathy with spheroids and literature review
BACKGROUND: Hereditary diffuse leukoencephalopathy with spheroids (HDLS), first described in 1984 is a rare disorder. Generally, it presents at adulthood with dementia, motor impairment, extrapyramidal abnormalities, and epilepsy. Definitive diagnosis is made by brain biopsy. Neuroimaging studies have revealed confluent white matter lesions predominantly in the frontal lobes, corpus callosum, and corticospinal tracts on conventional magnetic resonance imaging. Only a few reports showed diffusion restriction in the cerebral white matter; furthermore, rarer reports emphasized persistent foci of diffusion restriction as a diagnostic imaging marker. OBJECTIVE: Herein, we have aimed to illustrate the first biopsy-proven Turkish HDLS pedigree consisting of 18 persons in 3 generations which contained 4 affected individuals. MATERIALS AND METHODS: Four individuals in the pedigree of HDLS [two affected patients (patient III-1 and patient III-2) and two unaffected individuals (patient II-4 and patient III-5)] were investigated with conventional MRI and Diffusion-weighted imaging (DWI) using 1.5 Tesla (T) scanner. All four individuals were evaluated via neurological examinations and Mini-Mental State Examination. Brain biopsy study was performed on patient III-2. Finally, an extensive literature review involving pathology investigations and neuroimaging studies of HDLS patients was conducted. RESULTS: DWIs of two investigated patients showed deep white matter lesions with persistent diffusion restriction. Computed tomography imaging showed punctate mineralization in the lesions. Biopsy specimens of patient III-2 demonstrated axonal spheroids which were typical for HDLS. CONCLUSIONS: Via the presentation of our pedigree and literature review, we suggest HDSL as a first-line differential diagnosis in patients with undiagnosed adult-onset familial leukoencephalopathy, in particular, those with MRI lesions of frontal white matter and centrum semiovale associated with foci of diffusion restriction and mineralization. Finally, we think that the persistence of the diffusion restriction in deep white matter lesions should be kept in mind as a crucial neuroimaging sign for HDLS
Investigation of human leukocyte antigen in osteoarticular brucellosis
Background/aim: To determine the relationship between human leukocyte
antigen (HLA) antigens and osteoarticular brucellosis by evaluating HLA
Class I and II antigens in control subjects and patients developing
osteoarticular brucellosis in Turkey.
Materials and methods: The study included 28 patients with
osteoarticular involvement diagnosed with brucellosis and 100 controls.
The HLA Class I and II antigens were studied in isolated DNA samples
using sequence-specific oligonucleotide procedure.
Results: The mean age of the 28 patients and 100 controls was 42.3 +/-
20.2 years and 50.1 +/- 16.3 years, respectively. When the frequency of
HLA Class I was examined, HLA-A{*}02 and HLA-B{*}27 antigens were
detected in 50\% and 28.57\% of the patients, respectively. However,
there was no significant difference when compared to the control group.
Among the HLA Class I antigens, HLA-Cw{*}10 was determined in 35.71\% of
the patients and 17\% of the controls; the difference was significant (P
= 0.039).
Conclusion: In the development of brucellosis, the frequency of
HLA-Cw{*}10 among HLA Class I antigens was observed to be increased, and
HLA-Cw{*}10 was considered likely to cause predisposition to
brucellosis. Further studies to be performed on a higher number of
patients and controls could demonstrate that genetic factors play a role
in the diagnosis of osteoarticular brucellosis
Posterior Reversible Encephalopathy Syndrome in Henoch-Schonlein Purpura and Hemolytic Uremic Syndrome.
Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological syndrome, composed of symptoms such as headache, seizures, visual disturbances, lethargy, confusion, stupor, focal neurologic findings and radiological findings of bilateral gray and white matter abnormalities suggestive of edema in the posterior regions of the cerebral hemispheres. PRES is associated with significant morbidity and mortality if it is not expeditiously recognized. Magnetic resonance image (MRI) represents the most sensitive imaging technique for recognizing PRES. PRES has been seen in various clinical settings including renal disorders such as acute glomerulonephritis, lupus nephritis, nephrotic syndrome, and drug usage such as calcineurin inhibitors. We aimed to present two study cases for such clinical setting. In this report, we present two patients with PRES in whom the primary diagnosis was hemolytic uremic syndrome (HUS) and Henoch-Schonlein purpura (HSP). Both of them were treated with anticonvulsant and proper antihypertensive drugs. A repeated MRI scan of the head, an ophthalmologic assessment, and a follow-up electroencephalogram produced normal results with no sequelae. Early recognition of PRES as a complication during different diseases and therapies in childhood may facilitate the appropriate treatment, so that intensive treatment should be performed as soon as possible to avoid neurological sequelae
Cystatin C as biomarker of contrast-induced nephropathy in pediatric cardiac angiography
WOS: 000329790100002PubMed: 25536721Background/aim: The purpose of this study is to find the frequency of contrast-induced nephropathy (CIN) and to show the risk factors in the development of CIN and the diagnostic utility of serum cystatin C (CysC) and serum and urine neutrophil gelatinase-associated lipocalin (NGAL) during childhood following cardiac angiography. Materials and methods: In this prospective study, we studied 46 children with congenital heart disease. The levels of serum creatinine, serum CysC, and serum NGAL were measured at 4, 24, and 48 h, while levels of urine NGAL and urine creatinine were measured at 4 to 8 and 48 h following cardiac angiography. Results: According to serum creatinine levels, with a cutoff value of 4.1 mL/kg for development of CIN, sensitivity, specificity, area under the receiver-operating characteristic curve, and positive likelihood ratio were calculated as 69%, 70%, 0.67, and 2.29, respectively. The levels of serum CysC and serum creatinine significantly increased at 4, 24, and 48 h after the application of the contrast agent. Conclusion: The results of this study show that according to the definition of CIN, the incidence of CIN is significantly increased in pediatric patients with congenital heart disease. Moreover, the results support that serum CysC levels may allow the detection of CIN after cardiac angiography, like serum creatinine in present study
The effect of antidiuretic hormone on urine and serum electrolyte levels in children with primary monosymptomatic nocturnal enuresis
Background/aim: The data concerning the effects of desmopressin on
water/electrolyte disturbances of children with primary monosymptomatic
nocturnal enuresis (PMNE) are limited. In the present study we aimed to
evaluate the effect and tolerability of desmopressin on blood and urine
electrolytes and osmolality in PMNE.
Materials and methods: Thirty-five children with PMNE between the ages
of 5 and 15 participated in the study. Patients collected urine during
the daytime and acknowledged the night time fluid restriction before
starting to use the desmopressin tablets. The medication was taken
orally at least 1 h before bedtime. Blood and urine samples were
collected before the introduction of the treatment (day 0) and on the
third and seventh days of the administration of desmopressin to
determine osmolality and electrolyte levels.
Results: Thirty-five patients participated in the study. Twenty-one
patients (60\%) were male and 14 (40\%) were female. The mean age was
9.6 +/- 2.7 years. There were no significant changes in serum
osmolality, urine osmolality, and serum sodium concentration. Mean urine
calcium/creatinine ratio was 0.03 +/- 0.01 mg/mg at the beginning, 0.06
+/- 0.02 mg/mg on the third day, and 0.04 +/- 0.01 mg/mg on the seventh
day of the study. No significant changes were seen in urine
calcium/creatinine ratio before and after treatment.
Conclusion: Desmopressin appeared to be a well-tolerated drug and
provided a safe and effective treatment for children who were following
fluid intake restriction for PMNE
The Added Value of Diffusion Magnetic Resonance Imaging in the Diagnosis and Posttreatment Evaluation of Skull Base Chordomas
Objectives To determine the use of diffusion-weighted imaging (DWI) in the pre- and posttreatment evaluation of skull base chordomas. Design Retrospective study. Setting Tertiary care university hospital. Participants In total, 17 patients with histopathological diagnosis of chordoma who had magnetic resonance (MR) imaging and DWI were evaluated. Of them, 13 patients had posttreatment MR imaging including DWI. Main Outcome Measures Three apparent diffusion coefficient (ADC) values were obtained from tumor, and an ADC value was measured from pons for the purpose of normalization. ADC values of the subtypes of chordomas (typical and chondroid chordomas) were compared. Results Ten (59%) masses had increased signal on trace DWI at pretreatment evaluation. The mean ADC(entire) (tumor)/ADC(pons) was calculated as 1.55 +/- 0.44. The mean ADC(entire) (tumor) values of typical and chondroid chordomas were 1.26 +/- 0.29 x 10(-3) mm(2)/s and 0.99 +/- 0.46 x 10(-3) mm(2)/s, respectively. There was no statistically significant difference between ADC values of the subtypes (p > 0.05). For posttreatment evaluation, DWI enabled detection of residual tumor in the majority (85%) of cases. Conclusions DWI is useful in diagnosis and posttreatment evaluation of skull base chordomas. However, ADC values in our series did not distinguish the subtypes of chordomas.Wo
Neurologic involvement in atypical hemolytic uremic syndrome and successful treatment with eculizumab
WOS: 000316571400019PubMed ID: 23389237Atypical hemolytic uremic syndrome (aHUS) is associated with defective regulation of the complement pathway. Neurological involvement is the most common extrarenal complication and represents a major cause of mortality and morbidity. Two girls aged 11 and 6 years, respectively, developed aHUS and were treated immediately with plasma exchange (PE) and fresh frozen plasma infusion (PI). Although initial improvement in renal function was seen in both cases, the first patient showed progressing thrombotic microangiopathy (TMA) despite daily PE, and neurological manifestations (seizures, vision loss, loss of balance, and confusion) developed after 1 month. The second patient developed cerebral TMA (seizures, vision loss, and nystagmus) 6 days after initial presentation and remained unresponsive to PE/PI. Neurological symptoms were similar in both patients, even though they had different complement protein mutations. Treatment with eculizumab achieved complete control of neurological symptoms within 24 h and gradually normalized hematological and renal parameters in both children. Based on our two cases, we conclude that eculizumab is a rapid-acting, effective, and life-saving treatment for pediatric patients with aHUS and severe neurological involvement, which works by inhibiting complement-mediated TMA in the kidney and other organs, such as the brain.Alexion PharmaceuticalsAssistance with writing this manuscript was provided by Bioscript Stirling Ltd, UK, and funded by Alexion Pharmaceuticals. We give special thanks to Dr. Reyhan Diz Kucukkaya in the Department of Internal Medicine, Division of Hematology at Istanbul Bilim University, Istanbul, Turkey
Gliosarcoma of the Optic Nerves 15 years After Radiation Treatment For Hypophyseal Adenoma
"Gliosarcoma is a very rare mixed tumor in the central nervous system, consisting of glial and malignant mesenchymal elements. Gliosarcoma is considered a subtype of glioblastoma and termed as primary gliosarcoma. Secondary gliosarcoma is detected at subsequent surgery for previously resected and irradiated glioblastoma multiforme. We describe an unusual case with vision loss due to gliosarcoma, probably radiotheraphy-induced,15 years after radiation treatment for hypophyseal adenoma.
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