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Biomedical subjects

A Bakkaloglu

Publications and source records attributed to A Bakkaloglu.

At least 37 records · Page 2Linked to original sources
PubMed2001

Ataxia and peripheral neuropathy: rare manifestations in Henoch-Schönlein purpura.

Henoch-Schönlein purpura (HSP) is a multisystemic vasculitis. Nervous system involvement is usually underestimated. Headaches, mental status changes and seizures are the most frequent neurologic symptoms. Ataxia and mononeuropathy are both very rare. We present an 11-year-old boy with HSP who suffered from ataxia during the initial presentation and peripheral neuropathy at the time of a relapse. Brainstem vasculitic involvement was shown by magnetic resonance imaging, while cranial tomography was normal. All the neurologic symptoms and signs resolved following bolus methylprednisolone administration. Ten months later he had a second course of HSP with skin and renal involvement. A percutaneous renal biopsy, which was performed due to persistent hematuria, revealed mesangial proliferation with IgA deposition. During that period the patient experienced pain and numbness in the right foot and leg; electromyography showed signs of mononeuritis multiplex involving the right posterior tibial nerve. The patient responded to steroid therapy.

Ataxia↗
PubMed2001

Henoch-Schönlein purpura in Wiskott-Aldrich syndrome.

Wiskott-Aldrich syndrome (WAS) is a rare immune deficiency disease. Sialophorin glycosylation is defective in WAS. Although it is not very common, renal involvement including IgA nephropathy (IgAN) was reported. Abnormal glycosylation plays a key role in the pathogenesis of IgAN. We present an 8-year-old boy with WAS who had recurrent episodes of Henoch-Schönlein purpura with renal involvement following upper respiratory tract infections. His renal function did not deteriorate. Both IgAN and WAS have glycosylation defects, but there must be some other factors (genetic and environmental) to explain their rare association.

Humans↗
PubMed2001

Survey of factor V leiden and prothrombin gene mutations in systemic lupus erythematosus.

The two most common hereditary risk factors for thrombosis are factor V Leiden mutation and a prothrombin gene mutation. There is indeed a thrombotic tendency in patients with systemic lupus erythematosis (SLE) and it is not always associated with antiphospholipid antibodies. We aimed to determine the relationship between both factor V Leiden and prothrombin gene mutations and SLE. Using polymerase chain reaction (PCR) the factor V Leiden and prothrombin gene mutations were evaluated in 55 patients (20 children and 35 adults) with SLE. Although seven patients were found to have factor V Leiden mutation in the heterozygous state, two had the heterozygous G-->A (20210) prothrombin gene mutation. Although one had these two mutations concurrently, these two patients did not have thrombosis. The factor V Leiden mutation frequency (12.7%) was higher than that of our general population (7.1%). On the other hand, seven of the patients with SLE had a thrombotic event. Although of these seven, four (57%) had factor V Leiden mutation, three (43%) had no mutation. Of 48 patients with no thrombotic history, only three had the factor V mutation (6.25%). The prevalence of the factor V Leiden mutation in SLE patients with and without thrombosis was significantly different by Fisher's exact test (p<0.05). The risk of venous thrombosis in patients with factor V Leiden increased threefold compared to that in those without factor V Leiden mutation (odds ratio 20.1; CI 2.99-133.6). Although factor V Leiden mutation seems to play a role in the development of venous thrombosis in SLE, the development of thrombosis in SLE is multifactorial.

Adolescent↗
PubMed2001

Mutation frequency of Familial Mediterranean Fever and evidence for a high carrier rate in the Turkish population.

Familial Mediterranean Fever (FMF) is a recessive disorder characterised by episodes of fever and neutrophil-mediated serozal inflammation. The FMF gene (MEFV) was recently identified and four common mutations characterised. The aim of this study was to determine the carrier rate in the Turkish population and the mutation frequency in the clinically diagnosed FMF patients. We found a high frequency of carriers in the healthy Turkish population (20%). The distribution of the five most common MEFV mutations among healthy individuals (M694V 3%, M680I 5%, V726A 2%, M694I 0% and E148Q 12%) was significantly different (P<0.005) from that found in patients (M694V 51.55%, M680I 9.22%, V726A 2.88%, M694I 0.44% and E148Q 3.55%).

Alleles↗
PubMed2001

Polyarteritis nodosa in patients with Familial Mediterranean Fever (FMF): a concomitant disease or a feature of FMF?

BACKGROUND: Familial Mediterranean Fever (FMF) is caused by mutations in the gene encoding pyrin and is characterized by self-limited, recurrent attacks of fever and serositis. Vasculitis has been increasingly reported in FMF. A study evaluating the prognosis in FMF and polyarteritis nodosa (PAN) patients has not been reported previously. OBJECTIVES: To determine the special characteristics and the prognosis of PAN in FMF patients. METHODS: A questionnaire was used for the present survey. The setting was 7 referral centers from Turkey and Israel. Seventeen patients who were diagnosed with FMF and who developed PAN were included. PAN was diagnosed in those who met the Chapel Hill consensus criteria for microscopic polyarteritis or classic PAN. The clinical features of these 17 patients and the outcomes of their vasculitis were analyzed. RESULTS: The age at diagnosis of PAN in these FMF patients ranged from 3.5 to 37 years. All patients had constitutional symptoms, elevated acute phase reactants, and myalgia at the time PAN was diagnosed. The diagnosis of PAN was confirmed by renal angiography in 8 patients, by renal biopsy in 6 patients, and by muscle and/or nodule biopsies in 6 patients. A number of patients had definite features of both classic PAN and microscopic polyarteritis. CONCLUSIONS: When compared with other PAN patients, those with FMF tended to have a younger age at PAN onset, more frequent perirenal hematomas, and an overall better prognosis. The cases with overlapping features of microscopic and classic PAN pose a problem for the current classification of vasculitis. We suggest that the clinical representation of PAN in FMF patients has certain characteristics and may be a feature of FMF per se.

Adolescent↗
PubMed2001

Association of nitric oxide production and apoptosis in a model of experimental nephropathy.

BACKGROUND: In recent studies increased amounts of nitric oxide (NO) and apoptosis have been implicated in various pathological conditions in the kidney. We have studied the role of NO and its association with apoptosis in an experimental model of nephrotic syndrome induced by a single injection of adriamycin (ADR). METHODS: The alteration in the NO pathway was assessed by measuring nitrite levels in serum/urine and by evaluating the changes in vascular reactivity of the isolated perfused rat kidney (IPRK) system. Rats were stratified into control groups and ADR-induced nephropathy groups. These two groups were then divided into: group 1, animals receiving saline; and group 2, animals receiving aminoguanidine (AG) which is a specific inhibitor of inducible-NO synthase. On day 21, rats were sacrificed after obtaining material for biochemical analysis. RESULTS: Histopathological examination of the kidneys of rats treated with ADR revealed focal areas of mesangial proliferation and mild tubulointerstitial inflammation. They also had significantly higher levels of proteinuria compared with control and treatment groups (P < 0.05). Urine nitrite levels were significantly increased in the ADR-nephropathy group (P < 0.05). In the IPRK phenylephrine and acetylcholine related responses were significantly impaired in the ADR-nephropathy group. Apoptosis was not detected in controls. However, in the ADR-nephropathy group, numerous apoptotic cells were identified in the tubulointerstitial areas. Double staining revealed numerous interstitial apoptotic cells to stain for ED1, a marker for monocytes/macrophages. Treatment with AG prevented the impairment of renal vascular bed responses and reduced both urine nitrite levels and apoptosis to control levels. CONCLUSION: We suggest that interactions between NO and apoptosis are important in the pathogenesis of the ADR-induced nephrosis.

Animals↗
PubMed2001

The significance of antineutrophil cytoplasmic antibody in microscopic polyangitis and classic polyarteritis nodosa.

AIMS: To describe the distribution and features of classic polyarteritis nodosa (PAN) and microscopic polyarteritis (MPA) and the importance of antineutrophil cytoplasmic antibody (ANCA) in childhood PAN. METHODS: Classic PAN was diagnosed in 15 patients based on the presence of aneurysms on angiography in 10 patients and of necrotising vasculitis in medium sized arteries in five. MPA was diagnosed in 10 patients, based on characteristic findings at renal biopsy in six and by the presence of small sized necrotising arteritis in four. Serum ANCA was detected initially by indirect immunofluorescence (IIF) followed by an immunoassay for myeloperoxidase (MPO) in each case. RESULTS: The median age of the patients with classic PAN and MPA was 12 (range 8-17) and 9.5 (range 5-14) respectively. None of the patients with classic PAN had renal failure. Six of the patients with MPA presented with renal failure; four progressed to chronic renal failure. Clinically evident pulmonary-renal syndrome was present in three of the 10 patients with MPA. IIF for ANCA in classic PAN was negative in nine, showed mild staining patterns in six, and in one MPO-ELISA was mildly increased. IIF for ANCA in MPA revealed very strong perinuclear ANCA staining in nine and atypical staining in one. In MPA, median MPO-ELISA level was 42.5 EU/ml (range 20-250). Treatment of childhood PAN was satisfactory with effective treatment; however relapses did occur. CONCLUSION: ANCA is useful in the diagnosis and follow up of MPA.

Adolescent↗
PubMed2001

Comparative study of cefixime alone versus intramuscular ceftizoxime followed by cefixime in the treatment of urinary tract infections in children.

Urinary tract infections (UTI) can cause acute morbidity and may result in severe problems, including hypertension and reduced renal function. Diagnosis of UTI is extremely important since prompt treatment may prevent damage. In the present study we compared the efficacy of oral cefixime to initial intramuscular ceftizoxime followed by cefixime for the treatment of UTI in children. Fifty-four children were studied. They were randomized to receive either oral cefixime 8 mg/kg/day for 10 days or initial intramuscular ceftizoxime (Cefizox) 50 mg/kg twice a day for 2 days followed by oral cefixime for 8 days. Treatment groups were comparable regarding age, sex, clinical, and laboratory findings. Escherichia coli was isolated from 80% of patients. Repeat urine cultures were sterile within 24 hours in all children. Cure rates were comparable in both groups (92% vs 86% at the end of treatment). No serious adverse effects were observed. We concluded that oral cefixime is a safe and effective alternative treatment.

Adolescent↗
PubMed2001

Vascular endothelial growth factor in Henoch-Schonlein purpura.

OBJECTIVE: To investigate the possible role of vascular endothelial growth factor (VEGF) in the pathogenesis of Henoch-Schonlein purpura (IHSP). METHODS: Plasma VEGF levels were determined in 22 children by ELISA. Ten age matched healthy children served as controls. VEGF expression was evaluated by immunohistochemistry within the cutaneous vasculitic lesion as well as the nonaffected skin and in the skin specimens during the resolution of the disease. RESULTS. Plasma VEGF levels in pg/ml (mean +/- SE) were significantly higher during the acute phase (407.8 +/- 64.92) when compared with the levels seen during the resolution phase (202.17 +/- 26.6; p < 0.002) and in healthy controls (135 +/- 22.8; p < 0.001). Analysis showed that there was a correlation with erythrocyte sedimentation rate. C-reactive protein, white blood cell and platelet count. In all skin specimens, the intensity of the staining of VEGF in the epidermis, dermis, and vascular endothelial bed were evaluated and scored from (+) to (++++). VEGF expression in the epidermis and the vascular bed was more intense in resolving lesions compared with acute vasculitic lesions (p < 0.05). CONCLUSION: Our results suggest that as a potent permeability, chemotactic, and migratory factor, VEGF may play a crucial role in the morphological and functional changes of the vascular bed and inflammatory reaction in HSP.

Acute-Phase Reaction↗
PubMed2000

Mutation analysis of the entire PKD1 gene: genetic and diagnostic implications.

Mutation screening of the major autosomal dominant polycystic kidney disease (ADPKD) locus, PKD1, has proved difficult because of the large transcript and complex reiterated gene region. We have developed methods, employing long polymerase chain reaction (PCR) and specific reverse transcription-PCR, to amplify all of the PKD1 coding area. The gene was screened for mutations in 131 unrelated patients with ADPKD, using the protein-truncation test and direct sequencing. Mutations were identified in 57 families, and, including 24 previously characterized changes from this cohort, a detection rate of 52.3% was achieved in 155 families. Mutations were found in all areas of the gene, from exons 1 to 46, with no clear hotspot identified. There was no significant difference in mutation frequency between the single-copy and duplicated areas, but mutations were more than twice as frequent in the 3' half of the gene, compared with the 5' half. The majority of changes were predicted to truncate the protein through nonsense mutations (32%), insertions or deletions (29.6%), or splicing changes (6.2%), although the figures were biased by the methods employed, and, in sequenced areas, approximately 50% of all mutations were missense or in-frame. Studies elsewhere have suggested that gene conversion may be a significant cause of mutation at PKD1, but only 3 of 69 different mutations matched PKD1-like HG sequence. A relatively high rate of new PKD1 mutation was calculated, 1.8x10-5 mutations per generation, consistent with the many different mutations identified (69 in 81 pedigrees) and suggesting significant selection against mutant alleles. The mutation detection rate, in this study, of >50% is comparable to that achieved for other large multiexon genes and shows the feasibility of genetic diagnosis in this disorder.

Alleles↗
PubMed2000

MEFV mutations in Behçet's disease.

Familial Mediterranean fever (FMF) and Behçet's disease (BD), both inflammatory diseases, are highly prevalent in the Middle Eastern and Mediterranean populations. FMF is a Mendelian autosomic recessive disease linked to MEFV, a gene of unknown function. BD in contrast is a polyfactorial disease associated with the major histocompatibility complex. Because FMF and BD have epidemiological similarities, we asked whether the FMF gene was implicated in BD. We screened for the common MEFV mutations a cohort of 114 chromosomes from definite BD patients [meeting the criteria of the International study group] and probable cases [meeting at least two of these criteria]. We screened in parallel an ethnically matched cohort of FMF and control chromosomes. The M694V, V726A and E148Q mutations tended to be more frequent in definite BD (2.6%, 2.6%, and 5.2%, respectively) than in controls (0%, 0%, and 2.2%). The P706 polymorphism was found in 10.5% of the probable BD chromosomes, but in only 1.6% of the controls (p=0.01). Because some MEFV mutations were more frequent in BD than in controls, we suggest that they may act as additional susceptibility factors in BD.

Africa, Northern↗
PubMed2000

Renal involvement in polyarteritis nodosa: evaluation of 26 Turkish children.

Renal involvement is common in childhood polyarteritis nodosa (PAN). We report a retrospective analysis of the presentation and clinical course of 26 patients with PAN and renal involvement. The mean age was 9.3 years (range 1-14 years) and there were 12 boys and 14 girls. Renal symptoms at presentation were as follows: 3 had isolated proteinuria, 9 had nephritic syndrome, 2 had nephritic and nephrotic components, and 10 had renal failure with one of the above features. Two patients with isolated hypertension were diagnosed by angiography and classified as classical PAN. Patients either received prednisone p.o. alone (n=9), or prednisone plus cyclophosphamide p.o. (n=11), or pulse steroids with prednisone p.o. and cyclophosphamide (n=2); 4 did not receive any treatment. Patients who were given cyclophosphamide had a significantly better outcome than those who did not. We suggest that oral cyclophosphamide therapy and corticosteroids are effective in the treatment of PAN. The overall 1-year and 5-year survival rates of the patients were 72.5% and 60%, respectively. In conclusion, renal disease is a serious manifestation of PAN necessitating prompt and aggressive treatment.

Adolescent↗
PubMed2000

Mutations in ATP6N1B, encoding a new kidney vacuolar proton pump 116-kD subunit, cause recessive distal renal tubular acidosis with preserved hearing.

The multi-subunit H+-ATPase pump is present at particularly high density on the apical (luminal) surface of -intercalated cells of the cortical collecting duct of the distal nephron, where vectorial proton transport is required for urinary acidification. The complete subunit composition of the apical ATPase, however, has not been fully agreed upon. Functional failure of -intercalated cells results in a group of disorders, the distal renal tubular acidoses (dRTA), whose features include metabolic acidosis accompanied by disturbances of potassium balance, urinary calcium solubility, bone physiology and growth. Mutations in the gene encoding the B-subunit of the apical pump (ATP6B1) cause dRTA accompanied by deafness. We previously localized a gene for dRTA with preserved hearing to 7q33-34 (ref. 4). We report here the identification of this gene, ATP6N1B, which encodes an 840 amino acid novel kidney-specific isoform of ATP6N1A, the 116-kD non-catalytic accessory subunit of the proton pump. Northern-blot analysis demonstrated ATP6N1B expression in kidney but not other main organs. Immunofluorescence studies in human kidney cortex revealed that ATP6N1B localizes almost exclusively to the apical surface of -intercalated cells. We screened nine dRTA kindreds with normal audiometry that linked to the ATP6N1B locus, and identified different homozygous mutations in ATP6N1B in eight. These include nonsense, deletion and splice-site changes, all of which will truncate the protein. Our findings identify a new kidney-specific proton pump 116-kD accessory subunit that is highly expressed in proton-secreting cells in the distal nephron, and illustrate its essential role in normal vectorial acid transport into the urine by the kidney.

Acidosis, Renal Tubular↗
PubMed1999

Antineutrophil cytoplasmic antibodies in juvenile chronic arthritis.

We present the results of antineutrophil cytoplasmic antibody (ANCA) staining in patients with juvenile chronic arthritis (JCA). Thirty-one patients with an age range of 1-16 years were included in the study: 13, 15 and three patients, respectively, were classified having oligoarticular, polyarticular and systemic-onset disease. Indirect immunofluorescence analysis revealed ANCA staining in 45% of the patients. All, except one, revealed atypical pANCA staining. ELISA studies for anti-myeloperoxidase were positive in only one patient with typical pANCA staining. PR-3 ANCA tested negative in all patients. There were no significant correlations between ANCA staining and the clinical parameters of the patients. We conclude that, although the specificity of ANCA in JCA remains to be elucidated, it may be effective in the pathogenesis of the disease.

Adolescent↗
PubMed1999

Implications of certain genetic polymorphisms in scarring in vesicoureteric reflux: importance of ACE polymorphism.

Polymorphisms of the renin-angiotensin system (RAS) have been shown to affect renal prognosis in a number of diseases. We examined the influence of deletion (D) and insertion (I) polymorphism in the angiotensin I-converting enzyme (ACE) gene and the other polymorphic markers of RAS, and that of plasminogen-activator inhibitor-1 (PAI-1) on renal scarring in reflux nephropathy. Ninety-four children with third- or fourth-degree reflux were the subject of the study. They were stratified into two groups according to the technetium-99m-dimercaptosuccinic acid (DMSA) findings: the first group consisted of 41 patients with no scar formation. In the second group (n = 53), there was significant scar formation in the refluxing units. ACE levels, ACE gene, angiotensin-1 receptor (AT1) A1166C, angiotensinogen (ATG) M235T, and PAI-1 4G/5G polymorphisms were studied. In the second group with scarred kidneys, 18 patients had decreased renal function. The frequency of patients homozygous for the D allele was significantly greater in the second group with scar formation in the refluxing units compared with the first group of patients (P < 0.005). On multivariate analysis, the DD genotype was the only factor that had a significant impact on renal scar formation, introducing a 4.9-fold risk (P < 0.05, 95% confidence interval). We were unable to find any correlation with the presence ofDD genotype and hypertension, decreased renal function, proteinuria, or sex of the patient. DDgenotype correlated with the serum ACE levels (P < 0.005). AT1and ATGpolymorphisms and PAI-1 polymorphism did not correlate with scar formation or any of the parameters. This study provides evidence that the DDgenotype of ACE may be a genetic susceptibility factor contributing to adverse renal prognosis in reflux nephropathy; namely, scar formation. The role of the synergism between the aforementioned genetic polymorphisms can be enlightened with larger patient groups, possibly through multicenter studies.

Angiotensinogen↗
PubMed1999

Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness.

H+-ATPases are ubiquitous in nature; V-ATPases pump protons against an electrochemical gradient, whereas F-ATPases reverse the process, synthesizing ATP. We demonstrate here that mutations in ATP6B1, encoding the B-subunit of the apical proton pump mediating distal nephron acid secretion, cause distal renal tubular acidosis, a condition characterized by impaired renal acid secretion resulting in metabolic acidosis. Patients with ATP6B1 mutations also have sensorineural hearing loss; consistent with this finding, we demonstrate expression of ATP6B1 in cochlea and endolymphatic sac. Our data, together with the known requirement for active proton secretion to maintain proper endolymph pH, implicate ATP6B1 in endolymph pH homeostasis and in normal auditory function. ATP6B1 is the first member of the H+-ATPase gene family in which mutations are shown to cause human disease.

Acidosis, Renal Tubular↗