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Rezan Topaloglu

Publications and source records attributed to Rezan Topaloglu.

16 recordsLinked to original sources
PubMed2006

Is the CD14 C159T polymorphism effective in the development of secondary amyloidosis in Familial Mediterranean fever?

The most important complication of FMF is the development of amyloidosis. It is more common in the eastern Mediterranean compared to the US. The individual response to endotoxin may have a significant effect on the development of amyloidosis in FMF patients. To investigate the association between CD14 promotor C-159T polymorphism and development of amyloidosis, one hundred and forty-six patients who had FMF and had not developed amyloidosis; 26 with FMF and secondary amyloidosis and 92 controls were genotyped at the CD14-C159T locus. There was no difference between the genotype distribution of FMF patients (CC 30.0%, CT 50.0%, TT 20.0%) and controls (CC 29.2%, CT 45.8%, TT 25%); or between FMF patients with amyloidosis (CC 30.8%, CT 53.8%, TT 15.4%) or without amyloidosis (CC 29.2%, CT 45.8%, TT 25%). Our study shows that the CD14-C159T polymorphism is not associated with FMF or development of amyloidosis in the population studied. The effect of the genetic variations in the endotoxin signaling pathway under different environmental conditions such as high and low endotoxin exposure remain to be determined.

Adolescent↗
PubMed2006

A patient with hyper-IgD syndrome responding to anti-TNF treatment.

The hyperimmunoglobulinemia D periodic fever syndrome (HIDS) is caused by recessive mutations in the mevalonate kinase gene, which encodes an enzyme involved in cholesterol and nonsterol isoprenoid biosynthesis. The pathogenesis and treatment remains unclear. We describe a 6-year-old Turkish girl with severe disease. Her clinical features were accompanied with very high acute-phase reactants including a very high serum amyloid A level. The patient responded well to anti-tumor necrosis factor treatment. Our findings support the use of this anti-cytokine treatment in HIDS.

Anticholesteremic Agents↗
PubMed2006

Cyclosporine drug monitoring with C0 and C2 concentrations in children with stable renal allograft function.

Cyclosporin A (CsA) has a narrow therapeutic window and necessitates monitoring of blood concentration. We aimed to evaluate trough (C0) and second hour (C2) level after ingestion of drug monitoring in renal allograft recipients. In this retrospective study, 12 children eight boys and four girls; mean age at transplantation 14.6 +/- 3.7 yr (ranges: 7.0-19.0), mean age post-transplant 17.8 +/- 4.9 yr (ranges: 9.0-24.0) who were transplanted >6 months were enrolled in this evaluation. Ten were recipients of a living related donor and two deceased donor grafts. While six children were receiving CsA, steroids and azathioprine, the other six received CsA, steroids and mycophenolate mofetil. Clinical course, blood pressure, renal and liver function tests were recorded. Mean C0 and C2 were 96.2 +/- 59.5 and 504 +/- 305.4 ng/mL respectively. Mean serum creatinine level was 1.2 +/- 0.45 mg/dL and mean creatinine clearance (CrCl) was 89.2 +/- 36.8 mL/min/1.73 m2. There was a correlation between serum creatinine level, CsA dose and C2 levels,whereas,there was no correlation between age, blood pressure, CrCl and C2 levels. However, no correlation was found between C0 levels and any of the above parameters. In conclusion, our data suggest that C2 levels are correlated better with dose and serum creatinine level.

Adolescent↗
PubMed2005

Apoptosis and proliferation in childhood acute proliferative glomerulonephritis.

Acute proliferative glomerulonephritis is characterized by glomerular hypercellularity that can be caused by many different etiologies and pathogenetic mechanisms. A balance between cell birth by mitosis and cell death by apoptosis is crucial. In this study, apoptosis and the regenerative activity (Ki67/apoptosis index) were investigated in acute proliferative glomerulonephritis. Thirty-five children with biopsy-proven acute proliferative glomerulonephritis and five controls with MCD were studied retrospectively. According to the clinical outcome, patients were divided into 2 groups: group 1 (n =21) were patients with normal renal functions at follow-up; group 2 (n =8) were patients with end-stage renal failure or those who died. Immunohistochemical staining of proliferating cells (Ki67) was done. In situ end labeling of DNA was used to evaluate apoptosis. Glomerular cell apoptosis was 45% in the patients with acute proliferative glomerulonephritis and 3% in controls ( p <0.001). Apoptotic cells were identified in the tubulointerstitial compartment with higher and heavier immunostaining in patients than controls (p =0.001). Tubular proliferative index (= tubular proliferation/tubular apoptosis ratio) was significantly higher in group 1 patients than in group 2 patients (2.03+/-2% versus 0.32+/-0.6%, p =0.002). Tubulointerstitial regenerative ratio (=tubular proliferation/interstitial proliferation ratio) was significantly higher in controls than in patients (3.4+/-1.9 versus 1.52+/-0.8, p =0.01). In addition, it was significantly increased in group 1 patients when compared with those in group 2 patients (1.89+/-0.8 versus 0.73+/-0.2, p =0.001). Since 17 patients presented with postinfectious proliferative glomerulonephritis, which is known to exhibit better course, we also evaluated those parameters in patients with postinfectious proliferative glomerulonephritis separately. We found statistically significant differences only in the tubulointerstitial regenerative ratio, which was higher in postinfectious cases when compared with those in other cases [1.60 interquartile range (IQR) 1.54 versus 1.22 IQR 1.26, respectively, p =0.003]. In conclusion, tubular proliferative index and tubulointerstitial regenerative ratio might be useful parameters for predicting final functional outcome in acute proliferative glomerulonephritis. Further studies, however, are still needed to clarify the importance of these histopathological parameters.

Acute Disease↗
PubMed2005

An unusual presentation of classic polyarteritis nodosa in a child.

Classic polyarteritis nodosa (c-PAN) is a rare disease in adults and extremely rare in children. We report a 3-year-old girl with c-PAN who presented with disturbances of consciousness and hypertension. Cranial tomography showed a subarachnoid hemorrhage. Subsequent magnetic resonance imaging and magnetic resonance angiography demonstrated subarachnoid hemorrhage and acute ischemic lesions. Renal angiography revealed bilateral multiple aneurysms. Due to her constitutional symptoms and hypertension and radiological findings she was diagnosed as having c-PAN. She was successfully treated with hydralazine followed by angiotensin-converting enzyme inhibitor, calcium channel blocker, intravenous pulse methylprednisolone, and subsequently oral prednisolone and oral cyclophosphamide. To our knowledge this is the youngest patient with c-PAN presenting with subarachnoid hemorrhage. Malign hypertension at this young age deserves a meticulous investigation of the vascular origin. Furthermore, treatment with pulse methyl prednisolone followed by oral prednisolone and oral cyclophosphamide is a successful modality of treatment in such a life-threatening presentation of c-PAN in childhood.

Acute Disease↗
PubMed2004

The significance of IgA class of antineutrophil cytoplasmic antibodies (ANCA) in childhood Henoch-Schönlein purpura.

Antineutrophil cytoplasmic antibodies (ANCA) have been identified in a wide variety of vasculitic disorders, but it is controversial whether ANCA are present in the sera of patients with HSP. This prospective study was designed to assess the place of ANCA, particularly their IgA subclass, in HSP. Thirty-five patients (18 boys, 17 girls) aged 9.4 +/- 4 (3-16) years with a clinical diagnosis of HSP based on American College of Rheumatology (ACR) criteria were enrolled. Thirteen patients (6 boys, 7 girls) aged 8.3 +/- 5.5 (2-21) years with other vasculitides, consisting of classic polyarteritis nodosa (PAN) (n = 2); cutaneous polyarteritis nodosa (n = 1); acute infantile hemorrhagic edema (n = 2); acute urticarial vasculitis (n = 2); hypocomplementemic vasculitis (n = 1); and unclassified vasculitis (n = 5) served as disease controls and 10 healthy children served as normal controls. Twenty-five HSP patients and 7 disease controls were re-evaluated in the resolution phase that was described as 4-6 weeks after all symptoms subsided and all medications were stopped. Blood samples for ANCA and IgA rheumatoid factor (RF) were studied by indirect immunofluorescence (IIF) and ELISA, respectively. IgG ANCA was significantly lower in percentage in HSP patients (2.8%) than in disease controls (40%) (p = 0.002). In contrast, IgA ANCA in cytoplasmic pattern was detected in a significantly higher percentage of HSP patients (82.3%) in the acute phase compared to those in the disease controls (38%) (p = 0.004). In the resolution phase, IgA ANCA was negative in 88% of the patients (p = 0.001 for acute vs resolution phases). Neither IgG nor IgA ANCA were seen in normal controls. No relationship was found between disease severity of HSP and IgA ANCA. Positive IgA rheumatoid factor was present in only two patients with HSP. In conclusion, our results suggest that IgA ANCA may be useful to confirm the diagnosis of HSP in children.

Adolescent↗
PubMed2004

Monocyte chemoattractant protein-1 and interleukin-8 levels in children with acute poststreptococcal glomerulonephritis.

The infiltration of leukocytes into the glomeruli is a major factor in inflammatory glomerular damage in acute poststreptococcal glomerulonephritis (APSGN). Chemokines participate in leukocyte infiltration. The aim of the present study was to investigate the role of monocyte chemoattractant protein-1 (CCL2/MCP-1) and interleukin-8 (CXL8/IL-8) in APSGN with special emphasis on their role in the clinical course of renal disease. Twenty-one children with APSGN were studied. Serum and urinary CCL2/MCP-1 and CXL8/IL-8 levels were measured by ELISA. The relationships between urinary chemokines and the degree of proteinuria were investigated. Serum and urinary CCL2/MCP-1 levels were significantly higher in the acute phase than in the resolution phase and in controls ( P<0.05). Urinary CCL2/MCP-1 levels in the control group were significantly lower than in both the acute and resolution phases ( P=0.01 and P =0.001, respectively). In the acute phase, urinary CCL2/MCP-1 correlated with the extent of proteinuria ( r=0.58, P =0.006) but not with serum CCL2/MCP-1 levels ( r=0.21, P =0.36). Urinary and serum CXL8/IL-8 levels were significantly elevated in the acute phase compared with the resolution phase and controls ( P<0.05). A consistent increase in urinary CCL2/MCP-1 was found in the acute phase of patients with APSGN, and this correlates with the degree of proteinuria. Our results emphasize the important role of locally produced chemokines in immune-mediated glomerular injury.

Acute Disease↗
PubMed2004

Bone mineral density in children with familial Mediterranean fever.

The aim of this study was to evaluate bone mineral content (BMC), serum and urinary bone turnover parameters in patients with familial Mediterranean fever (FMF), an autosomal recessive disease characterized by recurrent episodes of inflammation of serous membranes. Demographic characteristics and MEFV mutations were defined in 48 children diagnosed with FMF (23 F, 25 M; median age 7.0 years (3.0-10.0)). We evaluated the blood counts, acute-phase proteins and serum and urinary bone turnover parameters during attack-free periods. The BMC and BA (bone area) of vertebrae L1-L4 were measured by DEXA. Thirty-eight age-, sex- and ethnicity-matched healthy children constituted the control group. Mean L1-L4 BMC in Group I (patients with two mutations) and II (patients with no or single mutations) were 15.49+/-5.99 g and 15.68+/-4.89 g, respectively, both significantly lower than the mean L1-L4 BMC of control patients, which was 19.59+/-6.7 g (p<0.05). Mean L1-L4 BMD in Group I, Group II and the control group were 0.466+/-0.066 g/cm(2), 0.487+/-0.085 g/cm(2 )and 0.513+/-0.079 g/cm(2), respectively. Mean z-scores in Group I, Group II and the control group were -1.87+/-0.74, -1.55+/-0.92 and -1.39+/-0.84, respectively. Mean L1-L4 BMD and z-score of Group I were lower than in the control group (p<0.05). ESR and SAA (serum amyloid A) levels were higher in Group I patients: 28.3+/-14.5 mm/h and 350+/-62 mg/l in Group I; and 20.5+/-11.7 mm/h and 190+/-68 mg/l in Group II, respectively. In conclusion, FMF patients had lower BMC, BMD and z-scores than a control group. We suggest that decreased BMD, BMC and z-score in FMF patients may be secondary to subclinical inflammation.

Bone Density↗
PubMed2004

An unusual pattern of arthritis in a child with Kawasaki syndrome.

Arthritis is reported in one-third of cases with Kawasaki syndrome. It may have an early or a late onset form. We present a 15-month-old-girl who had been referred with complaints of pain and swelling in her left shoulder. Physical examination revealed bulbar conjunctival injection, erythematous lips and pharynx, strawberry tongue, erythematous rash, edema and erythema of the left shoulder, left knee, right elbow and right wrist, and moderate distress in the left shoulder and left hip. She was diagnosed with Kawasaki syndrome, and intravenous immunoglobulin infusion (IVIG) 2 g/kg and aspirin (100 mg/kg/day) were instituted. The patient had two additional episodes of arthritis involving the hip joint on the 8th day, and the shoulder and metacarpophalangeal (MCP) and interphalangeal (IP) joints of her right hand on the 15th day. Turbid material was aspirated in both instances; Gram and Wright's staining of this material showed many leukocytes but no bacteria. A second dose of IVIG (1 g/kg) was given. At the end of the third week all extremities were painless, with a normal range of motion. Arthritis in our patient was the presenting sign, having a 'septic arthritis mimicking' and 'biphasic' pattern. Although the patient presented with severe and recurrent arthritis, which is significantly correlated with severe multisystem disease and the presence or development of coronary artery aneurysm, the response to IVIG was excellent.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Influence of Serum Amyloid A (SAA1) and SAA2 gene polymorphisms on renal amyloidosis, and on SAA/C-reactive protein values in patients with familial mediterranean fever in the Turkish population.

OBJECTIVE: To evaluate the effect of serum amyloid A (SAA) 1 and SAA2 gene polymorphisms on SAA levels and renal amyloidosis in Turkish patients with familial Mediterranean fever (FMF). METHODS: SAA1 and SAA2 gene polymorphisms and SAA levels were determined in 74 patients with FMF (39 female, 35 male; median age 11.5 yrs, range 1.0-23.0). All patients were on colchicine therapy. SAA1 and SAA2 gene polymorphisms were analyzed using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). SAA and C-reactive protein (CRP) values were measured and SAA/CRP values were calculated. RESULTS: The median SAA level was 75 ng/ml (range 10.2-1500). SAA1 gene polymorphisms were: a/a genotype in 23 patients (31.1%), a/beta genotype in 30 patients (40.5%), a/g genotype in one patient (1.4 %), beta/beta genotype in 14 patients (18.9%), beta/g genotype in 5 patients (6.8 %), and g/g genotype in one patient (1.4%). Of the 23 patients who had a/a genotype for the SAA1 polymorphism, 7 patients had developed renal amyloidosis (30.4%) compared to only one patient without this genotype (1/51; 2.0%); p < 0.001. SAA2 had no effect on renal amyloidosis. SAA1 and SAA2 genotypes had no significant effect on SAA levels. SAA/CRP values were significantly lower in patients with the SAA1a/a genotype, compared to other SAA1 genotypes: 0.16 (0.025-1.96) versus 0.23 (0.012-28.20), p < 0.05. CONCLUSION: SAA1a/a genotype is one genetic factor that confers a significant risk for amyloidosis in the Turkish FMF population. Neither the SAA1 nor SAA2 genotypes had a significant effect on SAA level.

Adolescent↗
PubMed2003

Urinary glycosaminoglycans in the course of familial Mediterranean fever.

UNLABELLED: Familial Mediterranean fever (FMF) is characterised by recurrent fever and serositis. The most important complication of the disease is amyloidosis. Cheap and non-invasive methods would be important in predicting or establishing the early diagnosis of amyloidosis. For this purpose, we studied the role of urinary glycosaminoglycans (GAG). The study group included 123 FMF patients without an attack and 11 patients with FMF associated amyloidosis. Ten healthy children and ten patients with primary nephrotic syndrome served as controls. In patients with amyloidosis, urinary GAG were lower than in patients with FMF, patients with nephrotic syndrome and controls (median and range: 8.54 mg hexuronic acid/g creatinine (1.87-25.5), 5.8 (1.7-17.26), 23.12 (8.74-28.06) and 19.25 (14.2-26.9) respectively, P<0.01). There was a significant negative correlation between the duration of the disease and urinary GAG ( r= -043, P=0.002). In 49 FMF patients with a low GAG, urinary GAG increased significantly after an increase in the colchicine dose (median and range: 6.64 mg hexuronic acid/g creatinine (1.77-19.39) and 9.45 mg hexuronic acid/g creatinine (2.36-28.9), P<0.01). CONCLUSION: These results suggest that urinary glycosaminoglycan levels may be a predictor of amyloidosis in patients with familial Mediterranean fever. We also suggest that effective colchicine doses may be monitored by following urinary glycosaminoglycan excretion.

Adolescent↗
PubMed2003

Mutational analysis of the xanthine dehydrogenase gene in a Turkish family with autosomal recessive classical xanthinuria.

BACKGROUND: Classical xanthinuria is classified into two categories: type I, deficient only in xanthine dehydrogenase (XDH) activity; and type II, deficient in both XDH and aldehyde oxidase. Both types present mainly with renal stones and lead to renal failure in some cases. We studied the molecular basis of xanthinuria in a Turkish family with two affected siblings. METHODS: We examined two brothers aged 1 and 14 years who presented with histories of passing several urinary stones. We measured their serum and urine levels of uric acid and oxypurine, chemically analysed their stones and performed allopurinol loading tests to diagnose the type of xanthinuria. In addition, we studied the coding regions of the XDH gene in family members. RESULTS: In the siblings, serum uric acid was undetectable and serum oxypurine was elevated. Laboratory studies showed that the stones that they passed were composed of xanthine, and both were diagnosed as having classical xanthinuria. The allopurinol loading tests indicated their xanthinuria to be type I. Within the entire coding region of the XDH gene, an A to T base change at nucleotide position 2164 was identified in the siblings, indicating a nonsense substitution from AAG (Lys) to TAG (Tyr) at codon 722. Concerning this novel nonsense mutation, restriction fragment length polymorphism (RFLP) analysis showed that the brothers were both homozygous, while the parents were heterozygous, and this confirmed the autosomal recessive inheritance of the XDH gene mutation. CONCLUSIONS: In a Turkish family, we identified a novel point mutation in the XDH gene responsible for classical type I xanthinuria. That both parents had a history of passing renal stones in spite of being heterozygous for that mutation may indicate that individuals with a heterozygous nonsense XDH mutation are more susceptible to nephrolithiasis than healthy individuals. This raises the point that individuals with a heterozygous XDH mutation may also present with renal stones.

Adolescent↗
PubMed2003

Mutations in the gene for familial Mediterranean fever: do they predispose to inflammation?

OBJECTIVE: To analyze 70 individuals who were found to have the Mediterranean fever (MEFV) gene for the presence of definite familial Mediterranean fever (FMF) and to assess if they were prone to clinical and laboratory inflammation. We also prospectively evaluated 72 patients with childhood rheumatic diseases for the presence of MEFV mutations. METHODS: Seventy patients with one MEFV gene mutation were reevaluated for the presence of a clinical FMF phenotype using a new set of criteria. They were also questioned for the presence of musculoskeletal symptoms and rheumatic diseases. They were sampled for erythrocyte sedimentation rates and C-reactive protein levels. A second group with childhood rheumatic diseases were diagnosed according to international criteria. RESULTS: Median age of the 70 heterozygous individuals was 12 years. About 1/3 (34.3%) were classified with clinical FMF phenotype according to the suggested criteria. Fifteen (21.4%) were classified as normal and 3 (4.3%) had recurrent abdominal pains but did not fulfill all criteria for clinical FMF. Overall, 28 (40.0%) had some form of rheumatic complaint and 15 (21.4%) had developed a rheumatic disease including Behçet's disease, a vasculitis, or acute rheumatic fever. The mean ESR and CRP levels were 45.47 +/- 33.05 mm/h and 4.00 +/- 6.73 mg/dl, respectively. Among the 72 patients with rheumatic diseases of childhood, 22 (30.5%) carried one or 2 mutations of the MEFV gene. The mutated allele frequency among patients with rheumatic diseases was significantly higher than those in controls (p < 0.05). Within this group, among the 59 patients with juvenile idiopathic arthritis 15 had mutations in the heterozygous or homozygous form. CONCLUSION: We confirm the acute phase response in the carriers for MEFV mutations. We suggest that these patients may have a tendency to develop certain manifestations due to an increased baseline of inflammation, and the presence of these mutations may affect their disease course when they develop rheumatic disease.

Adolescent↗
PubMed2002

Confirmation of the ATP6B1 gene as responsible for distal renal tubular acidosis.

Primary distal renal tubular acidosis (dRTA) type I is a hereditary renal tubular disorder, which is characterized by impaired renal acid secretion resulting in metabolic acidosis. Clinical symptoms are nephrocalcinosis, nephrolithiasis, osteomalacia, and growth retardation. Biochemical alterations consist of hyperchloremic metabolic acidosis, hypokalemia with muscle weakness, hypercalciuria, and inappropriately raised urinary pH. Autosomal dominant and rare forms of recessive dRTA are known to be caused by mutations in the gene for the anion exchanger AE1. In order to identify a gene responsible for recessive dRTA, we performed a total genome scan with 303 polymorphic microsatellite markers in six consanguineous families with recessive dRTA from Turkey. In four of these there was an association with sensorineural deafness. The total genome scan yielded regions of homozygosity by descent in all six families on chromosomes 1, 2, and 10 as positional candidate region. In one of these regions the gene ATP6B1for the ss1 subunit of the vacuolar H(+)-ATPase is localized, which has recently been identified as causative for recessive dRTA with sensorineural deafness. Therefore, we conducted mutational analysis in 15 families and identified potential loss-of-function mutations in ATP6B1in 8. We thus confirmed that defects in this gene are responsible for recessive dRTA with sensorineural deafness.

Acidosis, Renal Tubular↗