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Thirteen carnitine-deficient children (mean age, 16.1 +/- 2.56 years) on a three-times-weekly hemodialysis program for at least 1 year, and 11 healthy age matched children were involved in the study. All the patients had stable blood pressure and hemoglobin (Hb) levels with a maintenance dose of erythropoetin and none were digitalized. The total carnitine (TC) and free carnitine (FC) plasma levels were sampled prior to hemodialysis (HD) before and after 3 months of carnitine supplementation. A free carnitine (FC) to acylcarnitine (AC) ratio less than 4 was defined as carnitine deficiency. Intravenous L-carnitine was injected at a dose of 20-40 mg/kg three times weekly at the end of each dialysis session for a 3-month period. Echocardiographic examination was performed the day following HD, before and after carnitine treatment. Systolic and diastolic functions of the left ventricle, including the ejection fraction, were measured. Almost all the parameters were significantly different in controls and hemodialyzed patients. In carnitine-deficient hemodialyzed patients, 3 months of L-carnitine supplementation resulted in a significant increase in blood carnitine levels and the FC/AC ratio, but this was not associated with any significant improvement of cardiac function. Furthermore no significant changes were observed in plasma triglycerides, total cholesterol or other lipoprotein parameters before or after carnitine supplementation. Although there was a moderate increase in mean hematocrit (Hct) and Hb levels, these also did not reach statistically significant levels. These results suggest that the 3 months of carnitine supplementation is not sufficient to ameliorate cardiac function or increase Hb levels in children.

Malnutrition is prevalent in patients with end-stage renal disease (ESRD). Elevated serum leptin levels were thought to contribute to the anorexia and poor nutrition in renal failure. However, studies of the relationship between nutritional status and leptin concentration in chronic renal failure have yielded conflicting results. Plasma insulin-like growth factor I (IGF-I) level has been used as an indicator of nutritional status in patients with renal failure. The relationship between leptin and IGF-I is controversial. The present study was conducted with the aim of assessing the relationship between nutritional status, hyperleptinemia, and serum IGF-I. Seventeen ESRD patients (8 male, 9 female), aged 8-18 years (mean 15.3+/-3.3 years) and undergoing standard hemodialysis for 58.8+/-23.1 months were enrolled. Nine age-matched healthy children served as controls. In all patients, energy and protein intakes were 40-70 kcal/kg per day and 1-1.54 g/kg per day, respectively. Predialysis serum leptin and IGF-I levels were measured by radioimmunoassay. Body mass index was decreased in 13 (76%) patients. Triceps skinfold thickness (TST) was reduced (below the 5th percentile) in 7 (41%), whereas mid arm circumference and mid arm muscle circumference were reduced in 14 (82.5%) and 13 (76.5%), respectively. The median serum leptin level was significantly higher in patients than in controls [13.7 interquartile range (IQR) 30.50 pg/ml vs. 6.50 IQR 8.65 pg/ml, P=0.01]. The median serum IGF-I level was lower in the patients (205.1 ng/ml IQR 194.4 ng/l) than controls (418.0 ng/l IQR 310.5 ng/ml) ( P=0.01). IGF-I levels were more decreased in patients with severe malnutrition, defined according to TST (145.0 ng/ml IQR 125.5 ng/l) than patients without malnutrition (301.2 ng/l IQR 218.8 ng/ml) ( P=0.03) and healthy children ( P=0.002). Although statistically not significant, IGF-I levels tended to be decreased, while leptin levels were increased. The median plasma insulin concentration was 15 microU/ml (1.63-45.80) and did not correlate with leptin and IGF-I levels. In conclusion, the results of this study confirm the presence of high circulating plasma leptin levels, which may be one of the many factors involved in the pathogenesis of the malnutrition in children on hemodialysis.

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.

Membranoproliferative glomerulonephritis (MPGN) is a distinctive form of chronic glomerulonephritis. We present the results of our 96 paediatric patients with MPGN, reporting the survival and factors affecting prognosis in these patients. There were 64 boys and 32 girls with an age range of 2-17 (mean 10.6 +/- 3.7) years. All patients initially received oral corticosteroid therapy; remission was achieved in 22.9%. The unresponsive 77.1% either received cyclophosphamide and/or pulse methylprednisolone; 25.4% and 50.0% of these patients entered complete remission, respectively. The overall 1-year renal survivals of the MPGN patients were 90.1%, 5-year and 10-year survival rates were 81.9% and 61%, respectively. At multivariate analysis the factors affecting renal prognosis were haematuria at presentation (p0.05, risk factor 3.52), urinary protein/creatinine ratio (p0.05, risk factor 1.06 per 1 unit) and low haemoglobin values (p0.05, risk factor 1.43 for each 1 g/dl decrement). We suggest that more aggressive immunosuppression therapy should be instituted in patients unresponsive to steroids and that the aforementioned risk factors are higher for the development of renal failure.

Serum levels of tumor necrosis factor (TNF) and interleukin(IL-1) were studied in 20 HSP patients, in the acute phase and after remission, by ELISA technique. Skin biopsies obtained during the acute phase both from a lesion and from unaffected skin, as well as during remission, were immunostained for TNF, IL-1, and IL-6. The mean age of the patients was 9.8 (5-13). Mean serum TNF levels during the acute phase and remission were 14.0 +/- 8.9 pg/ml, and 6.8 +/- 2.4 pg/ml, respectively (p < 0.05). Serum TNF levels in patients with renal involvement (18.8 +/- 10.2 pg/ml) were significantly higher than in those without (10.8 +/- 6.5 pg/ml) (p < 0.05). Serum levels of IL-1 in the acute phase and remission were undetectable. All specimens showed leukocytoclastic vasculitis. Immunohistochemical studies revealed TNF, and a less intense IL-1 and IL-6 staining in the nucleated epidermal layer, with a granular, intracellular pattern. Staining was significantly increased in the affected skin during the acute phase. These results suggest that TNF, IL-1, and IL-6 may play a role as a mediator of inflammation in HSP.

It is very important to treat patients with upper urinary tract infections (UTIs) promptly and effectively because of the potential sequelae. In the present study we compare the efficacy of the two cephalosporins, ceftriaxone and cefotaxime, in childhood pyelonephritis. The study protocal included 10 days of drug therapy. Both in patients receiving ceftriaxone and cefotaxime, successful eradication was achieved at the second day of therapy. The overall cure rate was significantly better in the ceftriaxone group than the cefotaxime group in terms of recurrence and reinfections (p0.05). Furthermore, in the complicated group, ceftriaxone was slightly superior to cefotaxime, approaching significance in terms of preventing recurrent infections. No serious adverse effects were observed in either of the groups. The present study has shown that ceftriaxone exhibits favorable clinical and bacteriologic efficacy in patients with complicated and uncomplicated upper UTI. Once-daily injection of ceftriaxone in children is also an attractive advantage of the drug when compared to twice-daily cefotaxime.

The pathogenesis of vasculitis is complex and is yet to be fully elucidated, although it is known that inflammatory cells play a major role. Dysregulation of apoptosis and defective clearance of inflammatory cells could lead to the persistence of inflammation and excessive tissue injury. In this study we aimed to investigate Fas (CD95) and apoptosis on peripheral blood (PB) neutrophil and lymphocytes in Henoch-Schonlein purpura, both in the acute phase and after resolution to determine the role of apoptosis in this self-limited vasculitis. Leukocytoclastic vasculitis presenting with Henoch-Schonlein purpura (HSP) was diagnosed according to ACR 1990 criteria and confirmed by skin biopsy. Thirty-seven patients (22 boys, 15 girls) aged 2.5-17 years (9 +/- 3.3) were enrolled in the study. Expression of CD95 and apoptosis were investigated by the annexin/PI method on peripheral blood neutrophils and lymphocytes in both the acute and the resolution phases of the disease. The mean neutrophil and lymphocyte CD95 expression was 65.4 +/- 37.6% and 33.3 +/- 7.3%, respectively, in the acute stage and 62.8 +/- 44.2% and 41 +/- 20%, respectively, in the resolution ( P > 0.05). The percentage of apoptotic peripheral blood neutrophils and lymphocytes as determined by annexin positivity was 13.3 +/- 11.31% and 8.6 +/- 9.5%, respectively, during the acute phase and 4.6 +/- 3.4% and 3.1 +/- 3.1%, respectively, in the resolution (P = 0.002, P = 0.008). These results suggest that increased apoptotic process in the immune effector cells in the acute phase of the disease may play an important role in the early control of inflammatory response and repair in leukocytoclastic vasculitis, thereby contributing to the self-limited nature of the disease.

This study was designed to investigate T-lymphocyte subsets interleukin-2 receptor (IL-2R) expression and IL-2 production in minimal change nephrotic syndrome (MCNS). Peripheral blood T-lymphocytes and IL-2R expression were analysed using fluorescein isothiocyanatelabelled CD3, CD4, CD8 and CD25 monoclonal antibodies with flow cytometry. IL-2 production was determined by enzyme immunoassay. Ten children with MCNS in relapse and in remission were evaluated. Thirteen healthy children served as controls. The patients in relapse demonstrated a moderate decrease in the total absolute lymphocyte counts and CD8(+) T-lymphocytes compared with controls (P

In order to analyse their role as a specific marker of vascular damage and their value in monitoring disease activity the plasma concentrations of von Willebrand factor antigen (vWFAg) and the ristocetin cofactor (RiCoF) activities were determined in 43 children with vasculitis and 20 controls. These patients were sub-divided into three groups according to diagnosis: Henoch-Schönlein purpura (n = 18), polyarteritis nodosa (n = 16), and systemic lupus erythematosus (n = 9). High concentrations of vWFAg and activities of RiCoF were found in all the patient groups. vWFAg and RiCoF returned to normal as the patients became symptom free and remained above normal in those with continuing symptoms. The amount of vWFAg did not correlate with the acute phase reactants. vWFAg acted as a specific marker of vascular damage and was useful for the monitoring of disease activity both in small vessel vasculitis and systemic necrotising arteritis.

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder. Specific diagnostic criteria for BBS have now been defined. At least four of the five cardinal signs of mental retardation, obesity, hypogenitalism in men, distal limb anomalies, and progressive tapetoretinal degeneration of the retina are required for the diagnosis. Renal involvement has been described as a sixth cardinal feature. Chronic renal failure occurs in 30%-60% of patients. Hypertension has been noted in 50%-66% of cases. Renal abnormalities reflect a defect in maturation of the kidneys. We present a patient with BBS who had bilateral microaneurysms and occlusions in renal arterioles.

We aimed to evaluate the presence of peripheral antineutrophil cytoplasmic antibodies (p-ANCA) and cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) in children with SLE and to correlate its association of laboratory findings. Twenty-one children with SLE were studied. Serum samples in patients were tested by indirect immunofluorescence (IIF) slide kit (INOVA) for c-ANCA and p-ANCA and by ELISA for myeloperoxidase (MPO-ANCA) and proteinase 3 (PR3-ANCA). All the patients but two were quiescent for lupus at the time of sampling. Sixteen of 21 patients showed positive IIF staining whereas only 5 had MPO-ANCA and 2 of nine PR3-ANCA. The data suggests that SLE may be associated p-ANCA directed against additional target antigens rather than MPO and may be implicated in the pathogenesis of SLE or may be only non-specific antibodies developed in lupus.

A 16-year-old girl, diagnosed 1 year previously as having Sydenham chorea, was found to have systemic lupus erythematosus according to the American Rheumatism Association criteria. She now presented with pulmonary emboli and renal involvement and responded to immunosuppressive and anticoagulant therapy. The high levels of anticardiolipin antibodies returned to normal along with the clinical symptoms.We suggest that anticardiolipin antibodies are relevant to the development of chorea and thrombo-embolic complications and that these auto-antibodies should be sought for in similar cases.

Apoptosis is a programmed form of cell death. Recently much attention has been devoted to the role of apoptosis in rheumatological diseases. We have aimed to analyze apoptosis in the inflammatory pathway of familial Mediterranean fever (FMF).26 FMF patients and 12 age and sex matched controls were the subject of the study. Twelve of the patients were analyzed during an FMF attack whereas samples were obtained at least a week after an attack in 14. Four of the patients had renal amyloidosis. Whole blood was treated with ammonium chloride for RBC lysis. Subsequently the cells were stained with propidium iodide and annexin. Neutrophils and lymphocytes were gated separately for analysis by flow cytometry. We have also analyzed cellular Fas and Fas-ligand expression in these cells.The mean age of the patients was 12.00 +/- 3.17, and was not different than the control subjects. Erythrocyte sedimentation rate and CRP levels were significantly elevated in the attack group as compared to the attack-free group. The mean levels of neutrophil apoptosis in the FMF patients with an attack, attack-free and controls were 12.94 +/- 11.78, 6.60 +/- 7.83 and 3.98 +/- 4.27, respectively. Lymphocyte apoptosis in the same groups were 7.84 +/- 8.63, 2.75 +/- 2.33, and 1.22 +/- 0.93, respectively. Neutrophil and monocyte apoptosis was significantly increased during the attack as compared to the controls (p0.05). However lymphocyte apoptosis was not different between the aforementioned groups. On the other hand, lymphocyte apoptosis was significantly increased in the SLE patients (p0.05), whereas neutrophil apoptosis was not. Fas staining of neutrophils were not different between the groups (p0.05). On the other hand the difference between the groups for FasL was significant (p0.05).Neutrophil and monocyte but not lymphocyte apoptosis was significantly increased during FMF attacks reminding us that FMF is an autoinflammation of certain peripheral cells. The increased apoptosis in these patients maybe regarded as a response to clear the unwanted inflammatory cells. On the other hand the increased apoptosis maybe the explanation of the self-limited nature of the FMF attacks. Future studies will enlighten us on the significance of this increased apoptosis in the process of inflammation.

To investigate the possible role of vascular endothelial growth factor (VEGF) in the pathogenesis of Henoch-Schonlein purpura (IHSP).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; p0.002) and in healthy controls (135 +/- 22.8; p0.001). 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 (p0.05).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.

The aetiology of Takayasu's arteritis is unknown, but an association with tuberculosis has been reported. We report the case of a 12-year-old-boy with Takayasu's arteritis: his blood pressure was 150/90 mmHg and fundoscopic examination showed grade I hypertensive changes. A tuberculin test was positive and acid-fast bacteria were seen in the urine. Angiography revealed involvement of the descending aorta, thoracic aorta and upper abdominal aorta, with fusiform enlargement and no filling of the left renal artery. He was started on prednisolone therapy, with cyclophosphamide being added subsequently. Despite vigorous treatment, including three courses of nitroprusside infusion, the severe hypertension persisted and his blood pressure became regulated only after left nephrectomy. Acid-fast bacteria were seen in the nephrectomy material. The exact role of Mycobacterium tuberculosis in the pathogenesis of Takayasu's arteritis is still unknown. In this patient the tuberculin test was positive and acid-fast bacteria were seen in both the urine and nephrectomy material. This finding is suggestive of the association between tuberculosis and the disease process.

Anti-myeloperoxidase (MPO) antibodies are associated with the development of anti-neutrophil cytoplasmic antibody (ANCA)-related vasculitis. The imbalance between the protease-antiprotease activity in the neutrophils has been implicated in the pathogenesis of ANCA-related vasculitis. Ceruloplasmin is an acute-phase protein that has antiproteinase and antioxidant properties and inhibits MPO activity. We attempted to study the association between serum ceruloplasmin and ANCA in childhood vasculitis. Forty-five ANCA-related diseases were included in the study. The age range was 4-16 years. Patients were divided into two groups based on indirect immunofluorescence and/or ELISA specificity (MPO). Twenty-six patients had p-ANCA- and 19 patients had c-ANCA-positive disease. Nine patients with Henoch-Schonlein purpura were studied as an ANCA-negative control group. Serum ceruloplasmin levels in p-ANCA-, c-ANCA-positive patients, and controls were 125.85+/-93.48 mg/dl, 59.79+/-17.60 mg/dl, and 64.34+/-18.77 mg/dl, respectively, and were significantly higher in patients with p-ANCA ( P

(1992). Amyloidosis of Juvenile Chronic Arthritis in Turkish Children. Scandinavian Journal of Rheumatology: Vol. 21, No. 5, pp. 257-259.

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.

To investigate the prevalence of juvenile chronic arthritis (JCA), familial Mediterranean fever (FMF), and Behçet's disease in Turkish children through a field survey.The field survey was based on cluster centering with 2 level strata. A total of 46,813 children were screened. For the diagnosis of chronic arthritis and Behçet's previously suggested criteria were used. We have developed criteria for the diagnosis of probable FMF. Children previously diagnosed to have these diseases were also defined and included.JCA was found in 6.4/10,000. 2.8/10,000 children were previously diagnosed as FMF (minimum phenotype frequency). Together with the probable diagnosis of FMF, the prevalence increased to 9.3/10,000. The findings were also compared with those of our center. None of the 46,813 children had Behçet's disease.The prevalence of chronic arthritis is similar to the other childhood populations reported. However, FMF has a very high prevalence.

BACKGROUND Protein-energy malnutrition (PEM) is associated with increased morbidity and mortality in haemodialysis (HD) patients. Insulin-like growth factor I (IGF-I) has proved to be a sensitive marker of malnutrition, while interleukin-1 (IL-1beta) and tumour necrosis factor (TNF) have been found to be raised in catabolic states. METHODS We have investigated the nutritional status of 17 chronic renal failure (CRF) paediatric patients (8 boys, 9 girls) on maintenance HD. Eight predialysis CRF children (5 boys and 3 girls; mean creatinine 5.1+/-3.2 mg/dl) and 10 healthy children served as control groups. PEM was defined according to anthropometric measurements (triceps skinfold thickness (TST), mid-arm circumference (MAC), and mid-arm muscle circumference (MAMC)). These were correlated with serum IGF-I, IL-1, TNF-alpha, transferrin, and albumin (all sampled before the HD session). RESULTS In the HD group, TST was reduced in 41.2% of the patients, whereas MAC and MAMC were reduced in 82.4 and 76.5% respectively. TST was depleted in only one of the predialysis CRF children. The degree of reduction in MAC and MAMC were 62.5 and 62.5% respectively. Median serum IGF-I level was decreased in both HD and predialysis CRF patients (205.1 interquartile range (IQR) 194.4 microg/l and 258.8 IQR 155.0 microg/l respectively) compared to the healthy children (418.0 IQR 310.5 microg/l) (P=0.0009 and P=0.01 respectively). Within the HD group, IGF-I levels were lower in patients with malnutrition defined according to TST (145.0 IQR 125.5 microg/l) compared to children with normal TST (301.2 IQR 218.8 microg/l) (P=0.05). IGF-I levels of the HD patients with malnutrition according to TST was also lower than the predialysis CRF patients and healthy children (P=0.04 and P=0.002 respectively). Serum IL-1beta was undetectable in all groups. Median serum TNF-alpha levels were higher in HD and predialysis CRF patients compared to healthy children, albeit statistically insignificant. There was no correlation between TNF-alpha, transferrin or albumin and anthropometric parameters. CONCLUSIONS Our results support the high prevalence of malnutrition in CRF children, which becomes more pronounced when treatment by HD is initiated. We suggest that determination of IGF-I levels in childhood HD patients in conjunction with anthropometric measurements is useful for identification of malnutrition. We have not been able to demonstrate the catabolic effects of cytokines on this state of protein energy malnutrition.

Familial Mediterranean fever (FMF) is a genetically transmitted disease characterized by recurrent attacks of fever and serositis. The most important complication of this disease is the development of amyloidosis. We present our analysis of 425 FMF patients without and 180 with amyloidosis (123 FMF having amyloidosis type 1 and 57 FMF having amyloidosis type II). The male female ratio was higher in the amyloidosis population (111/69) when compared to the FMF population (225 200) (P = 0.048). Consanguinity rate was the same among FMF and amyloidosis groups. However, a family history of amyloidosis was significantly more frequent in the amyloidosis group (P = 0.00001). Multivariate analysis has revealed that in FMF patients, the presence of a family history of amyloidosis plus consanguinity has a 6.04 fold increased risk of amyloidosis (P0.0001). The 5-year chronic renal failure free survival was 43.1% and 18.7% in type I and type II amyloidosis, respectively. The time interval to develop chronic renal failure after the development of amyloidosis was 4.8 in type I and 3.0 years in type II. respectively. We found ten cases of Henoch-Schönlein Purpura and nine of polyarteritis nodosa among our patients. The significance of the association between FMF and vasculitis awaits to be clarified. Among the FMF patients put on colchicine therapy (435), only 10 (2.3%) have developed amyloidosis confirming that this drug protects from amyloidosis.Since the presence of a familial history of amyloidosis has been defined as the most important risk factor in the development of amyloidosis, we suggest that additional genetic factors may be operative in the development of amyloidosis.

Familial Mediterranean fever (FMF) is an autosomal recessive condition that is almost entirely restricted to the non-Askhenazi Jews, Arabs, Armenians, and Turks. Genetic linkage study of a large group of non-Turkish families has previously mapped the FMF locus to the 16p13.3 region and shown that this locus resides 0.305 cM distal to D16S246. Furthermore, allelic association has also been shown with D16S3070 (75%) and D16S3275 (66%). However, no genetic heterogeneity has been described for any of the three major reported groups of FMF families. Here, we describe the genetic linkage relationship of the fourth major group of Turkish families and report the first evidence for genetic heterogeneity of this condition. Two point linkage analysis and haplotype inspection of 15 DNA markers from the reported region of the FMF locus identified tight linkage in a group of six Turkish FMF families. A maximum lod score of 9.115 at theta = 0.00 was observed for D16S3024. Nine other DNA markers provided similar evidence of linkage with lod score values of above 5.21. However, two other FMF families were completely unlinked to this region of chromosome 16. Haplotype construction of DNA markers in five consanguineous linked families showed that a segment of homozygosity has been conserved for D16S3070 and D16S2617. No other DNA markers showed any such conservation. Therefore, we suggested that these two markers reside in close proximity to the FMF locus. Furthermore, we observed 80% allelic association with D16S2617 but no association with D16S3070 or any other DNA markers from the FMF critical region. In summary, we conclude that our Turkish families are also linked to the reported FMF locus at 16p13.3, there is a genetic heterogeneity for this condition at least in our group of Turkish families, and D16S2617 is in linkage disequilibrium in the Turkish FMF families. Combination of this study with previously published observations suggests that the FMF locus resides between D16S246 and D16S3070/D16S2617 and within a region of about 250-300 kb.

The immunoinflammatory pathogenesis of juvenile chronic arthritis (JCA) involves the activation of many pathways including various cytokines. We have evaluated the levels of interleukin(IL)-1, IL-6 and IL-8 in 29 JCA patients. The age range was 1-16 with a mean of 10.1. A disease activity score was developed on the basis of: 1. constitutional symptoms and/or morning stiffness, 2. presence of joint swelling, 3.warmth, 4.limited range of motion, and 5.joint pain. This score correlated very significantly with laboratory disease activity markers such as erythrocyte sedimentation rate (ESR) and CRP (both p = 0.006) and also correlated with IL-1 and IL-6 levels. The levels of IL-1 decreased in four of the five patients with improved disease activity. IL-6 but not IL-1 correlated significantly with the number of inflamed joints (p = 0.013); IL-6 also strongly correlated with rheumatoid factor supporting this cytokine's role in B cell induction (p = 0). Haemoglobin values correlated negatively with the activity index, ESR, CRP, IL-1 and IL-6. IL-8 did not correlate with disease activity markers. In the systemic patients all cytokines tended to be higher. Our data suggest that interleukins 1 and 6 are effective in the pathogenesis of JCA. Whether cytokines may be used for monitoring therapy may be clarified with further studies.

Anaemia is a common manifestation of juvenile rheumatoid arthritis (JCA). We have evaluated 26 JCA patients with anaemia and compared their laboratory parameters to those without anaemia. In the patients with anaemia, activation criteria such as erythrocyte sedimentation rate (ESR) and CRP were significantly higher than in those without anaemia. Anaemia was present in all systemic JCA patients and was present in 42% and 78% of the oligoarticular and polyarticular types, respectively. Serum iron levels and transferrin saturations were low in all, whereas serum iron-binding capacities of the patients were normal. Mean ferritin level was 249pg/l (range 8.46-1000pg/l). There was a significant correlation between ferritin levels and CRP and ESR (r = 0.48 and r = 0.55 respectively) (both p0.05). Epo levels were normal. Twelve (60%) of the bone marrow aspiration specimens stained positive for iron whereas 40% stained negative; there were also changes suggestive of myelodysplasia. Sideroblasts were also decreased in number. Thus, in these patients iron is not sufficiently transferred to the erythroid series and/or cannot be used by erythroblasts, accompanied by a possible absolute iron deficiency. Thus we suggest that the iron in JCA tends to be stored in the form of ferritin, not in an accessible form and impaired metabolism along with other factors are effective in the anaemia of JCA.

Hyperoxaluria is characterized by nephrocalcinosis and nephrolithiasis on radiological examination and may also result in diffuse deposition of calcium oxalate crystals in multiple extrarenal organs (oxalosis). In two cases, the renal findings of primary hyperoxaluria were diagnosed by ultrasound and computed tomography scans. In addition to renal involvement, both patients had liver involvement, and one patient had cardiac involvement.

An 8-year-old male, who had Down syndrome associated with systemic lupus erythematosus (SLE), is described. He also had a partial complement 4 deficiency. This case is a reminder that the physician should be aware of the possibility of an immune defect in a male presenting with SLE at a young age. The question of whether the association of Down syndrome with SLE is coincidental or whether there is a predilection for autoimmune disorders in Down syndrome is discussed.

A 13-year-old boy presented with acute hemolytic anemia a few days after mumps infection. The ensuing hemoglobinuria resulted in acute renal failure in this child, which was corrected with fluid and alkali therapy. We draw attention to this uncommon complication of mumps and the need for careful evaluation.

A 15-year-old girl who developed "brown tumour" as a complication of secondary hyperparathyroidism while on maintenance haemodialysis therapy is described. Parathyroidectomy with implantation of a portion of one parathyroid gland was performed. Recovery of the lesion was noted 6 months after surgery and a ratio of about 1/12 was found when the systemic parathormone level was compared to that obtained from the vein draining the implanted parathyroid tissue. We would like to emphasize that signs and symptoms of secondary hyperparathyroidism should be sought for before complications develop; and if medical therapy is unsuccessful, this type of surgery is a justified option.

Familial Mediterranean fever is characterised by recurrent and self limited attacks of fever and polyserositis and its devastating complication is the development of renal amyloidosis. In order to detect the presence of early glomerular and tubular damage in patients with familial Mediterranean fever and to assess the possible role of beta 2-microglobulin in the inflammatory attacks of this disease, serum and urine beta 2-microglobulin concentrations and microalbuminuria were evaluated in these patients. A total of 20 patients with familial Mediterranean fever were studied on and off colchicine treatment; seven of these patients developed a familial Mediterranean fever attack when they were off treatment. During the familial Mediterranean fever attacks serum beta 2-microglobulin concentrations decreased, whereas fractional excretion of beta 2-microglobulin, urine beta 2-microglobulin creatinine, and urine albumin/creatinine ratios increased. We conclude that glomerular and tubular functions deteriorate during the attacks. Further studies are needed to discover the effector(s) causing these transient glomerular and tubular disorders.

In this study rhEPO, 70 U/kg, was subcutaneously administered two times a week for eight weeks to twelve nondialysed patients with renal anaemia and chronic renal failure. Renal function tests, blood pressure, Hb, Hct, FENa and Na-K-ATPase enzyme activity before and after administration of rhEPO have been studied. We have searched for correlations, if any, between these parameters. After the treatment period mean Hb concentration and mean Hct values increased from 7.5 +/- 0.3 to 8.6 +/- 0.5 g/dl and from 22.5 +/- 1.2 to 26.7 +/- 1.6%, respectively (p0.05), whereas no significant differences between pretreatment and posttreatment Cr and CrCl values were found (p0.05). No changes in blood pressure were found throughout the study. While mean FENa decreased from 10.2 +/- 1.6 to 6.15 +/- 1.05% (p0.05), mean Na-K-ATPase enzyme activities decreased from 0.120 +/- 0.016 to 0.095 +/- 0.025 mumol Pi/h/mg protein (p0.05) after treatment. In conclusion, subcutaneous administration of rhEPO, at doses of 70 U/kg twice a week in nondialysed patients increased Hb and Hct values. A significant decrease of FENa was observed after rhEPO treatment and there was no correlation between Na-K-ATPase enzyme activity and FENa.

A 12-year-old uraemic patient who had received a renal allograft from a donor of unknown cytomegalovirus (CMV) serology was evaluated for subfebrile fever and pericardial effusion. Viral DNA was detected with PCR. The patient responded very well to Ganciclovir therapy. This patient highlights the importance of donor serology and the need for careful evaluation of even minor signs and symptoms of CMV disease.

Plasma levels of atrial natriuretic peptide (ANP) and of endothelin (ET) were significantly elevated (87.7 +/- 13.9 pg/ml and 79.7 +/- 10.8pg/ml, respectively) during the acute phase of acute poststreptococcal glomerulonephritis (APSGN). Plasma renin levels were normal, fractional excretion of sodium (FENa) was 0.5 +/- 0.1% and creatinine clearance (CCr) averaged 82.2 +/- 18.3 ml/min per 1.73 m2. In the recovery phase of the disease (n = 12), levels of ANP (23.6 +/- 6.7 pg/ml) and ET (43.1 +/- 2.4 pg/ml) fell and were not significantly different from those measured in 11 control subjects. FENa increased to 1.3 +/- 0.1% and CCr to 113.5 +/- 12.1 ml/min per 1.73 m2 (all values mean +/- standard error). ANP did not correlate with PRA, blood pressure, CCr or FENa. There was an inverse relationship between the ET level and FENa in the acute phase of the disease (r = 0.489, P0.05), but no significant correlation between ET and blood pressure, PRA, CCr or ANP was found. We suggest that, despite the sodium retention, the increased ANP level in APSGN indicates unresponsiveness of the kidneys to ANP; the increased ET levels may contribute to this.

We have evaluated 11 patients for the presence of late potentials in an attempt to investigate whether pulse methylprednisolone exerted its arrhythmogenic effect via this mechanism. All patients received pulse steroid therapy for their glomerulopathies. One of the patients developed bradycardia, no electrocardiographic abnormalities were present in the rest of these patients. Late potentials were not detected in any of the patients. Thus, in this preliminary study we have not been able to demonstrate that pulse steroid therapy plays a role in the genesis of late potentials.

The appearance of red blood cells in the urine may be the result of disease of any segment of the urinary tract. To determine whether there might be a distinguishing characteristic of the urinary red cells which appear during glomerular disease but is absent in other urinary tract diseases, the mean corpuscular volumes (MCV) of urinary and blood erythrocytes were measured by a Coulter counter in 34 children with haematuria. Diagnosis of the underlying renal or urinary tract disease was made by clinical and laboratory findings, including radiological investigations, renal biopsy and cystoscopy. The ratio of the urinary erythrocyte MCV to that in blood (Umcv/Bmcv) was compared with the diagnosis. The Umcv/Bmcv ratio was less than 1.0 in all children with glomerular disease and was greater than 1.0 in all but 1 of the patients with non-glomerular disease. This study suggests that the Umcv/Bmcv ratio provides a simple and useful technique for distinguishing between glomerular and non-glomerular haematuria. Such determination would help in guiding appropriate diagnostic evaluation.

Four and two male sibs of two separate families who had biopsy-proven membranoproliferative glomerulonephritis (MPGN) are presented. In the first family four sibs of the first-degree consanguineous marriage showed the clinical picture of nephrotic syndrome without hypocomplementaemia at initial laboratory findings. In the second family two affected sibs showed nephrotic and nephritic syndromes on admission. Family investigations showed normal serum complement, immunoglobulins, T-cell subsets, urine analysis, and serum biochemistry. HLA typing in the two families revealed a common antigen HLA A2 in all affected sibs. Some other reports give suggestive evidence of MPGN in siblings but this is the first report that showed the occurrence of MPGN in four sibs. Our data strengthened the concept that genetic factors are involved in the development of MPGN but additional immunogenetic studies will shed light on the genetic aspects of the disease.