N Tümer

Ankara University, Ankara, Ankara, Turkey

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Publications (49)153.2 Total impact

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    ABSTRACT: The aim of the present study was to assess the correlation of immunohistochemical subtyping with clinical diagnosis in order to achieve useful epidemiological data regarding amyloidosis in Turkish patients. We carried out immunohistochemical studies on 128 biopsies from various sites of 111 patients with biopsy-proven amyloidosis and, based on the results, classified the patients. We assessed the correlation of immunohistochemical subtype with clinical diagnosis and gathered epidemiological data. The sites most biopsied were kidney and rectum, followed by the testicle, liver, small intestine and bladder. Amyloid deposits showed positive staining with a single antibody in 120 biopsies. Pure amyloid A (AA) positivity was seen in 113 biopsies; six biopsies were positive for amyloid lambda (AL) and one for beta2-microglobulin (beta2MG). The clinical diagnoses of 81 patients (98 biopsies all AA positive) were suggestive of familial Mediterranean fever (FMF). Also AA positive were eight patients with tuberculosis, seven patients with rheumatoid arthritis, four patients with bronchiectasis and one patient with Crohn's disease. The biopsies from seven patients clinically suspected to have plasma cell dyscrasias were AL positive. One patient undergoing haemodialysis was beta2MG positive. Two patients without definite diagnoses showed double or triple positivity, which could not be interpreted and classified immunohistochemically. This study demonstrates that the predominant association of AA amyloidosis is with FMF. It also suggests that the routine immunohistochemical study of patients with amyloidosis who are of certain ethnic backgrounds suffices for classifying the subtype of amyloid fibril protein and the related disease.
    Nephrology Dialysis Transplantation 09/2005; 20(8):1721-5. · 3.37 Impact Factor
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    ABSTRACT: Familial Mediterranean fever (FMF) is an autosomal recessive disorder. Although the pathogenesis of the disease is not yet completely understood, enhanced acute-phase responsiveness is considered to be one of the most important mechanisms. The presence of high levels of antistreptolysin O (ASO) antibodies and streptococcus-associated diseases, such as acute poststreptococcal glomerulonephritis (AGN) and acute rheumatic fever (ARF), has been reported in patients with FMF. In order to better understand the effect of FMF on antistreptococcal antibody response, we measured ASO and antideoxyribonuclease B (anti-DNAse B) levels in patients with FMF and compared them with those in healthy controls. The study consisted of two parts. In the first step, antistreptococcal antibody levels were analysed in 44 patients with FMF and 165 healthy children who had no history or clinical evidence of upper respiratory tract infection (URTI) for the last 4 months. In the second step, antistreptococcal antibody levels were measured in 15 patients with FMF and 22 healthy controls in response to documented group A beta-haemolytic streptococcal pharyngitis. In the first part of the study, ASO and anti-DNAse B levels in patients with FMF were found to be significantly higher than those in healthy controls (P<0.001). In the second part, ASO and anti-DNAse B titres were found to be significantly higher in patients with FMF than in controls (P<0.001 and <0.05, respectively) 4 weeks after a positive throat culture. We concluded that patients with FMF have an exaggerated response to streptococcal antigens and might be prone to poststreptococcal non-suppurative complications, such as ARF.
    Clinical Rheumatology 09/2002; 21(5):378-81. · 2.04 Impact Factor
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    ABSTRACT: Background: Cardiovascular complications are the most frequent cause of death in patients with end-stage renal failure (ESRF). We aimed to investigate systolic and diastolic functions in children with ESRF.Methods: Thirty-nine children with ESRF (17 on continuous ambulatory peritoneal dialysis (CAPD), eight on hemodialysis and 14 on predialysis) were examined to assess systolic and diastolic functions by echocardiography and ultrasound Doppler. Left ventricular systolic and diastolic functions were measured both in patients and age-matched healthy controls (n = 20) and the indices of cardiac performance were compared.Results: Increased left ventricular mass index (LVMI) and decreased volume/mass ratio with normal systolic left ventricular function was found in patients, as compared with controls. Left ventricular diastolic dysfunction was observed in dialysis patients. In most of these patients, left ventricular isovolumic relaxation time was prolonged, except in CAPD patients. The peak of late diastolic flow (A) velocities were increased with a reduction of the early diastolic flow velovity (E) – the E/A ratio. The E velocities were unchanged in all patients as compared with controls. Our data indicated an abnormality of myocardial relaxation in patients with ESRF. We found no relationship between E/A ratio and LVMI. Among three groups of patients, the LVMI and diastolic abnormalities were highest in the hemodialysis group indicative of poor control of hypervolemia and hypertension.Conclusions: The technique of CAPD has some advantages as a renal replacement therapy for preserving cardiac functions as compared with hemodialysis. However, it must be remembered that patients with hemodialysis have features that effects cardiac status, such as higher volume load and higher afterload (hypertension).
    Pediatrics International 03/2002; 44(1):18 - 23. · 0.88 Impact Factor
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    ABSTRACT: Cardiovascular complications are the most frequent cause of death in patients with end-stage renal failure (ESRF). We aimed to investigate systolic and diastolic functions in children with ESRF. Thirty-nine children with ESRF (17 on continuous ambulatory peritoneal dialysis (CAPD), eight on hemodialysis and 14 on predialysis) were examined to assess systolic and diastolic functions by echocardiography and ultrasound Doppler. Left ventricular systolic and diastolic functions were measured both in patients and age-matched healthy controls (n = 20) and the indices of cardiac performance were compared. Increased left ventricular mass index (LVMI) and decreased volume/mass ratio with normal systolic left ventricular function was found in patients, as compared with controls. Left ventricular diastolic dysfunction was observed in dialysis patients. In most of these patients, left ventricular isovolumic relaxation time was prolonged, except in CAPD patients. The peak of late diastolic flow (A) velocities were increased with a reduction of the early diastolic flow velocity (E)--the E/A ratio. The E velocities were unchanged in all patients as compared with controls. Our data indicated an abnormality of myocardial relaxation in patients with ESRF. We found no relationship between E/A ratio and LVMI. Among three groups of patients, the LVMI and diastolic abnormalities were highest in the hemodialysis group indicative of poor control of hypervolemia and hypertension. The technique of CAPD has some advantages as a renal replacement therapy for preserving cardiac functions as compared with hemodialysis. However, it must be remembered that patients with hemodialysis have features that effects cardiac status, such as higher volume load and higher afterload (hypertension).
    Pediatrics International 03/2002; 44(1):18-23. · 0.88 Impact Factor
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    ABSTRACT: Neurologic manifestations can accompany systemic diseases, and primary disease can be identified with a careful history, physical examination, and laboratory investigations. A 14-year-old girl with paraplegia and absence of deep tendon reflexes in the lower extremities after 2 days of vomiting and diarrhea was referred to our pediatric neurology department with a diagnosis of Guillain-Barré syndrome. Short stature, dehydration, motor and mental retardation, bilateral cataracts, glaucoma, and band keratopathy were detected on physical examination. Hypopotassemia and severe metabolic acidosis were found on biochemical examination. Her paraplegia improved after appropriate fluid and electrolyte replacement, but metabolic acidosis persisted after cessation of intravenous therapy, and isolated proximal renal tubular acidosis was detected. Because she had isolated proximal renal tubular acidosis and other abnormalities, she was diagnosed with Donckerwolcke-Winsnes syndrome.
    Journal of Child Neurology 11/2001; 16(10):770-1. · 1.39 Impact Factor
  • Pediatrics International 11/2001; 43(5):508-10. · 0.88 Impact Factor
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    ABSTRACT: Various immunological abnormalities leading to impaired immune status have been described in uraemic adults; however, few data are available for uraemic children. In this study, peripheral blood total lymphocyte count and lymphocyte subsets (CD3+, CD4+, CD8+, CD16+, CD20+) were evaluated, skin tests with PPD and Candida antigens were performed, and serum immunoglobulin (IgG, IgA, IgM) and complement (C3, C4) levels were measured in 30 children with end-stage renal failure (10 before dialysis, 10 on continuous ambulatory peritoneal dialysis, and 10 on haemodialysis) and the results compared with those of 15 healthy controls. The data showed significant lymphopenia in predialysis and haemodialysis groups. No significant change was observed in the CD4+/CD8+ ratio or in the percentages of lymphocyte subsets in either group studied, while the absolute values of some lymphocyte subsets were significantly lower in all groups as compared with controls. In skin test evaluation, only the patients in the predialysis group showed a significantly decreased response to Candida antigen. The serum immunoglobulin levels were significantly decreased in the continuous ambulatory peritoneal dialysis group as compared with the control group. Our results, together with those of other paediatric studies, reported in the literature, suggest that uraemic children are not immunocompromised, though the effects of uraemia may cause some variation in their immune status.
    Nephron 09/2001; 88(4):379-81. · 13.26 Impact Factor
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    ABSTRACT: A 14-year-old boy with classic polyarteritis nodosa (cPAN) and a clinical picture resembling rapidly progressive glomerulonephritis (RPGN) is described. He had severe hypertension, malaise, weight loss, fever, myalgia, and rapid deterioration of renal function. Renal biopsy revealed acute necrotizing vasculitis. Angiography showed small saccular aneurysmatic dilatations in the intrarenal branches of the right renal artery and the intrahepatic branches of the hepatic artery. cPAN was diagnosed and pulse methylprednisolone (MP), pulse cyclophosphamide (CYC) and subsequently oral prednisolone were given. Clinical and laboratory findings improved dramatically and remission was attained rapidly. The patient has remained in remission for the last 11 months. cPAN should be considered in patients who present with severe systemic symptoms and hypertension. Progressive renal insufficiency can occur during the acute course of cPAN due to renal vascular involvement without glomerulonephritis. Prompt and aggressive corticosteroid and cytotoxic therapy is essential to suppress disease activity and to maintain remission.
    Pediatric Nephrology 03/2001; 16(2):148-50. · 2.94 Impact Factor
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    ABSTRACT: We compared the frequencies of seven MEFV mutations (M694V, M680I, V726A, M694I, K695R, R761H, E148Q) and the clinical findings in 20 Turkish FMF patients who had not developed amyloidosis by the age of 40 years in the absence of colchicine therapy, with those in 27 Turkish amyloidosis patients. No mutation frequency, including that of M694V, was different between the two groups. Family history of amyloidosis and parental consanguinity were noted to be higher in the amyloidosis group. The seven mutations do not appear to be sufficient to explain the development of amyloidosis in Turkish FMF patients. Other genetic factors may be important for this association.
    QJM: monthly journal of the Association of Physicians 11/2000; 93(10):681-4. · 2.36 Impact Factor
  • Pediatric Nephrology 09/2000; 14(8-9):882-3. · 2.94 Impact Factor
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    ABSTRACT: Familial Mediterranean fever (FMF) is an autosomal recessive disease. It is characterized by recurrent febrile episodes in association with peritonitis, pleuritis, and arthritis. Progressive systemic amyloidosis is the most important complication of FMF that inevitably leads to chronic renal failure. Recently, the gene for FMF, MEFV, has been cloned and four missense mutations have been described: M694V, M680I, V726A, and M694I. Initial studies have suggested that the presence of the M694V mutation carries a significant risk for the development of amyloidosis. In this study, we present seven families, in which at least two individuals have been diagnosed with FMF and at least one with amyloidosis. Among 18 individuals, in whom molecular testing was performed for the four aforementioned mutations, ten had amyloidosis. None of these ten individuals was found to be homozygous for the M694V mutation. In three families, there were two sibs with amyloidosis. None of the sib-pairs with amyloidosis was found to have the same genotype. There were two or more sibs with the same genotype in four families. Only one sib from each family developed amyloidosis in these families. These results provide evidence that FMF patients without the M694V mutation are also at risk for the development of amyloidosis. Particular mutations themselves do not appear to be sufficient to explain the occurrence of amyloidosis in all cases with FMF.
    Clinical Genetics 07/2000; 57(6):430-4. · 3.94 Impact Factor
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    ABSTRACT: Familial Mediterranean fever (FMF) is an autosomal recessive disease. It is characterized by recurrent febrile episodes in association with peritonitis, pleuritis, and arthritis. Progressive systemic amyloidosis is the most important complication of FMF that inevitably leads to chronic renal failure. Recently, the gene for FMF, MEFV, has been cloned and four missense mutations have been described: M694V, M680I, V726A, and M694I. Initial studies have suggested that the presence of the M694V mutation carries a significant risk for the development of amyloidosis. In this study, we present seven families, in which at least two individuals have been diagnosed with FMF and at least one with amyloidosis. Among 18 individuals, in whom molecular testing was performed for the four aforementioned mutations, ten had amyloidosis. None of these ten individuals was found to be homozygous for the M694V mutation. In three families, there were two sibs with amyloidosis. None of the sib-pairs with amyloidosis was found to have the same genotype. There were two or more sibs with the same genotype in four families. Only one sib from each family developed amyloidosis in these families. These results provide evidence that FMF patients without the M694V mutation are also at risk for the development of amyloidosis. Particular mutations themselves do not appear to be sufficient to explain the occurrence of amyloidosis in all cases with FMF.
    Clinical Genetics 05/2000; 57(6):430 - 434. · 4.25 Impact Factor
  • Nephron 04/2000; 84(3):276-7. · 13.26 Impact Factor
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    ABSTRACT: Familial Mediterranean Fever (FMF) is an autosomal recessive disease characterized by recurrent self-limited attacks of fever accompanied by peritonitis, pleuritis and arthritis. Approximately 5% of individuals with FMF have been reported to have Henoch-Schönlein purpura (HSP) and about 1% have polyarteritis nodosa (PAN). Protracted febrile myalgia is another vasculitis-associated clinical entity among patients with FMF. Recently, the gene responsible for FMF, MEFV, has been cloned and four missense mutations (M680I, M694V, V726A and M694I) have been described. In this report, we present clinical and laboratory findings and mutation results of 23 children with FMF-associated vasculitis. HSP, PAN and protracted febrile attacks have been diagnosed in 11, 2 and 10 children, respectively. Mutation analysis shows that 3 children are homozygotes for the M694V mutation and 11 are compound heterozygotes for 2 of the studied mutations. M694V/V726A mutations were identified in 8, M694V/M694I in 2 and M680I/M694V in 1 of these children. In six children only one mutation was found and in three none of the studied mutations were identified. This study confirms that most children with FMF-associated vasculitis have identifiable mutations in the MEFV gene. Environmental and/or other genetic factors are possibly involved in the pathogenesis of vasculitis in FMF; elucidation of these mechanisms will help to understand pathogenesis of childhood vasculitides.
    Acta Paediatrica 03/2000; 89(2):177-82. · 1.97 Impact Factor
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    Nephrology Dialysis Transplantation 03/2000; 15(2):246-8. · 3.37 Impact Factor
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    ABSTRACT: The prevalence of different types of bone disease in chronic renal failure (CRF) has changed significantly during the last decade. The aim of the present study is to evaluate the spectrum of bone disease in children with CRF undergoing continuous ambulatory peritoneal dialysis (CAPD). Seventeen children with CRF on CAPD aged 7-20 years were evaluated. All patients had received regular vitamin D and calcium carbonate therapy during the 6 months preceding the bone biopsy. Serum calcium, phosphate, alkaline phosphatase and immunoreactive parathyroid hormone (iPTH) levels were measured and hand X-rays were performed. Transiliac bone biopsies were analyzed for histologic diagnosis. High turnover renal osteodystrophy (ROD) was the most common bone disease, present in eight patients (47%). Five patients (29%) had low turnover bone disease, and four (24%) had mixed ROD. The mean age of the high turnover ROD group was higher than that of the low turnover group (14 +/- 3 vs. 11 +/- 3 years, P < 0.05). Seven of the nine patients who had tubulo-interstitial nephritis were found to have high turnover bone disease. In contrast, none of the patients with glomerulonephritis exhibited high turnover bone lesions. Mean serum calcium levels were found to be significantly higher in the low turnover group compared with the patients with high turnover bone disease (P < 0.001). A serum iPTH level > 200 pg/mL was 100% sensitive and 66% specific in identifying patients with high turnover ROD. The spectrum of bone disease of the children with CRF undergoing CAPD seems to depend on the rate of CRF and primary disease. The risk of developing overt hyperparathyroid bone disease is high in children with slowly progressing forms of renal pathology and especially in those with tubulo-interstitial disease. In contrast, children with glomerular diseases who had a more rapidly progressive course may have a lesser risk of developing high turnover bone disease. The results of the present study indicate that even routinely prescribed regular vitamin D therapy early in the course of disease may lead to low turnover bone lesion in small children who have CRF due to rapidly progressive forms of renal pathology.
    Pediatrics International 03/2000; 42(1):53-7. · 0.88 Impact Factor
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    ABSTRACT: Differences in clinical manifestations of familial Mediterranean fever (FMF) between different ethnic groups have been documented. The FMF gene was recently cloned and four missense mutations (Met694Val, Met680Ile, Val726Ala, and Met694Ile) that account for a large percentage of the patients were identified. The results of initial mutation studies have led to the hypothesis that phenotypic variation of the disease may be attributable to the existence of some of these mutations. The purpose of this study was to evaluate whether this phenotypic variation is associated with the existence of particular mutations in Turkish FMF patients living in Turkey. Four missense mutations and genotype-phenotype correlation were investigated in 167 Turkish FMF patients. The patients were grouped according to the presence of the Met694Val and the Met680Ile mutations, and 12 clinical parameters were compared between the groups. The presence of the Met694Val mutation was not found to be associated with a severe form of the disease or the development of amyloidosis. Arthritis frequency was found to be lower in the patients with homozygous Met680Ile mutation. None of the four missense mutations is associated with a severe disease or the development of amyloidosis in Turkish FMF patients living in Turkey. The influence of unknown environmental factors and/or the presence of other genetic changes are necessary to explain the phenotypic variation of the disease and the development of amyloidosis.
    Rheumatology 02/2000; 39(1):67-72. · 4.21 Impact Factor
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    ABSTRACT: Familial Mediterranean fever (FMF) is a recessive inherited disorder affecting Sephardic Jews, Arabs, Armenians and Turks. The gene responsible for FMF was recently cloned and several disease-associated mutations have been described. We have evaluated seven MEFV mutations in 460 chromosomes of 230 unrelated patients with FMF living in Turkey, using PCR methods. The M694V allele accounted for 43.5% of the alleles studied and 19.1% of the patients were homozygous. The M680I, V726A and M694I mutations were responsible for 12.0%, 11.1% and 2.8% of the patients respectively. R761H, K695R and E148Q were rarely encountered. Two thirds of the disease alleles were attributed to three common mutations: M694V, M680V and V726A, but only 54% of the patients carried one or two of the three mutations. Adding the four rarer mutations increased these figures to 72% and 60%, respectively. Altogether, 79.6% of the patients bore at least one of the main mutations, and 84.3% carried at least one of the seven mutations studied. The 28 patients suffering also from amyloidosis carried at least one of five mutations, M694V being the most common. These results suggest that the origin of FMF in Turkey is heterogenous, all common mutations are associated with amyloidosis. Further, rapid and accurate molecular diagnosis of FMF is feasible in most cases. Hum Mutat 15:118–119, 2000. © 2000 Wiley-Liss, Inc.
    Human Mutation 12/1999; 15(1):118 - 119. · 5.21 Impact Factor
  • Pediatric Nephrology 10/1999; 13(7):637-8. · 2.94 Impact Factor
  • M Ekim, N Tümer, S Bakkaloğlu
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    ABSTRACT: The incidence of tuberculosis (TB) is increasing worldwide. Due to an impairment of cellular immunity, patients with chronic renal failure are susceptible to reactivation of TB. Seventy patients were treated by continuous ambulatory peritoneal dialysis (CAPD) in our pediatric nephrology department during the years 1989-1997. TB was diagnosed in 4 patients, representing 5.7% of all CAPD patients in our department. One patient had extrapulmonary (TB osteomyelitis) and the others had pulmonary TB. All patients were treated with antituberculous drugs. Two patients with pulmonary TB were cured. Symptoms improved in the other 2 patients but they died at home for unknown reasons. We recommend that all children in regions of high prevalence of TB should be investigated for TB, especially if they have a cough or fever of unknown etiology.
    Pediatric Nephrology 10/1999; 13(7):577-9. · 2.94 Impact Factor

Publication Stats

589 Citations
153.20 Total Impact Points

Institutions

  • 1992–2002
    • Ankara University
      • • Department of Pediatric Nephrology
      • • Department of Pediatrics
      • • Faculty of Medicine
      Ankara, Ankara, Turkey
  • 2000
    • Virginia Commonwealth University
      • Department of Pediatrics
      Richmond, VA, United States