Colchicine treatment in children with familial Mediterranean fever.

Prophylactic colchicine therapy has been shown to be a safe and effective method of eliminating the attacks and preventing the development of amyloidosis in patients with familial Mediterranean fever (FMF). However, information about effective dosages that control FMF attacks and prevent amyloidosis in childhood is not available. The aim of this study is to determine the 'effective colchicine dose' for children in terms of body weight and surface area. Sixty-two (34 male, 28 female) children with FMF were selected and colchicine treatment was initiated by giving 0.5-1 mg/day to each patient. The dose was gradually increased up to a maximum 2 mg/day in unresponsive patients; mean duration of therapy was 45.6 +/- 35.5 months. When the 'optimal effective dosage' (i.e. the one that reduced the frequency of attacks and ESR, CRP and fibrinogen levels during the attack-free period) was achieved, the optimal effective dose was calculated according to the body weight and body surface area for each patient. Based on these values 'mean colchicine dose' was computed for the study group and values for different age groups were evaluated. Mean colchicine doses according to the body weight and surface area of the whole group were found to be 0.03 +/- 0.02 mg/kg/day and 1.16 +/- 0.45 mg/m(2)/day, respectively. It was shown that children less than 5 years of age might need colchicine doses as high as 0.07 mg/kg/day or 1.9 mg/m(2)/day. These dosages are approximately 2.5-3 times more than the 'mean colchicine dose' for children aged 16-20 years. These results clearly show that small children need higher doses of colchicine in order to control their attacks. Thus, we conclude that colchicine, when given according to body weight or body surface area, would be more effective in childhood.

Antistreptococcal response is exaggerated in children with familial Mediterranean fever.

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.

Testing apparatus and experimental procedure for position specific normalization of electromyographic measurements of distal upper extremity musculature.

OBJECTIVE: An apparatus and procedure are described to determine position specific normalization coefficients for surface EMG of upper extremity musculature. STUDY DESIGN: Thirty-nine subjects were tested three times. Repeatability of EMG measurements across test sessions was determined by computing intraclass correlation coefficients. Two-way analysis of variance was used to test upper extremity position dependent differences in EMG measurements. BACKGROUND: EMG measurements are susceptible to error from skin movement and muscle length changes, both of which may occur when upper extremity positions vary. Normalization of the EMG signal without consideration for such positional influences may lead to erroneous conclusions regarding muscle activation during functional tasks. METHOD: An apparatus was designed that allowed subjects to perform three repetitions of maximum elbow flexion, forearm pronation, wrist extension, and wrist flexion with the forearm in neutral and pronated positions. Surface EMG was sampled from eight muscles. Mean EMG on maximum voluntary contraction was computed, and resting EMG was subtracted to obtain EMG normalization coefficients. RESULTS: Upper extremity position affected the EMG normalization coefficient for biceps brachii, which was lower in the pronated position, and extensor carpi radialis, which was higher in the pronated position (P<0.00625). CONCLUSIONS: The apparatus accommodates various combined positions of the elbow, forearm and wrist. The normalization procedure is efficient for testing subjects who are being observed during functional tasks. Only two muscles were affected by upper extremity position, but group trends were not always consistent with individual behavior. This method would ensure the use of appropriate EMG normalization coefficients regardless of individual variation. RELEVANCE: This method is effective for normalizing EMG signals using task specific upper extremity positions. It may be used to test isometric exertions of distal upper extremity musculature for clinical and research purposes.

Familial Mediterranean fever (FMF)-associated amyloidosis in childhood. Clinical features, course and outcome.

OBJECTIVE: Familial Mediterranean fever (FMF) is an autosomal recessive disorder of childhood characterized by attacks of fever and serositis. Renal amyloidosis is the most important complication of the disease that determines the prognosis. METHODS: Forty-eight Turkish FMF patients with amyloidosis who have been followed at the two hospitals in Ankara were included in this study. RESULTS: All patients with amyloidosis had been symptomatic for FMF at the time of the diagnosis (Phenotype I), none had received regular colchicine therapy and all presented with proteinuria. Ten of them had asymptomatic proteinuria; 38 had nephrotic syndrome and 8 of them had renal insufficiency (CRI) as well, at the time of the diagnosis. Regular colchicine therapy was commenced to all of the patients. At the end of observation period of 4.5 +/- 2.23 years (range 2-12 yrs) on treatment, nephrotic syndrome resolved in 13 patients and proteinuria was lost in 5 of them. None but 2 of the patients who were diagnosed at proteinuric stage progressed to end stage renal failure (ESRF). Seven MEFV mutations (M694V, M680I, V726A, M694I, K695R, R761H, E148Q) were systematically investigated in 32 patients. Six of the seven studied mutations were found in these patients and clinical diagnosis was confirmed by mutation analysis in 24 patients. Eight patients were found to have mutations on one of the alleles. CONCLUSION: Amyloidosis is the most serious complication of FMF. Colchicine treatment ameliorates the progression of renal disease in the patients who presented with proteinuria and even with nephrotic syndrome. No correlation between the outcome of the patients with nephrotic syndrome and the degree of proteinuria and/or serum albumin levels at the initiation of treatment were noted. Progression to ESRF seems inevitable despite colchicine therapy after the development of CRI in patients with FMF associated amyloidosis.

Spectrum of renal osteodystrophy in children on continuous ambulatory peritoneal dialysis.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Genotype-phenotype correlation in a large group of Turkish patients with familial mediterranean fever: evidence for mutation-independent amyloidosis.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Blood pressure nomograms for children and adolescents in Turkey.

In order to obtain data on blood pressure (BP) distribution in Turkish children, a total of 5,599 Turkish children from birth to 18 years were studied. BP rises with age, and both systolic and diastolic BP showed a positive correlation with height and weight in both sexes. As the sampling was representative of Turkish children at different ages, the mean systolic and diastolic BP levels were compared for each age with the results reported in the study of the Second Task Force. The mean systolic and diastolic BP of Turkish children and the increase with growth and development were different from the Second Task Force study. Genetic, ethnic, and environmental factors were suggested to be responsible for this variation. In conclusion, normal BP curves should be applied with caution in childhood, and every population should use their own normal standards to define a measured BP level in children.

Familial Mediterranean fever--renal involvement by diseases other than amyloid.

BACKGROUND: In patients with familial Mediterranean fever (FMF) renal involvement is usually in the form of AA amyloidosis. There is increasing evidence that renal involvement may be due to diseases other than amyloid as well. METHODS: Amongst 302 children with FMF we observed and followed 28 with typical clinical and laboratory features of vasculitis. The diagnosis of FMF was established according to the Tel Hashomer criteria. RESULTS: Polyarteritis nodosa, protracted febrile attacks and Henoch-Schönlein purpura were diagnosed in 4, 13, and 11 patients, respectively. The presentation was often difficult to distinguish from FMF attacks, but protracted febrile attacks lasting several weeks, hypertension, thrombocytosis, and dramatic responses to corticosteroid therapy that were observed in many cases were different from what is observed in classical FMF. CONCLUSIONS: We suggest that FMF, perhaps as a consequence of impaired control of inflammatory responses, predisposes to vasculitis with renal involvement.

Pseudoxanthoma elasticum: a rare cause of hypertension in children.

We describe an 11-year-old girl with severe renin-dependent hypertension. She had characteristic cutaneous, ocular, and vascular signs of pseudoxanthoma elasticum (PXE), and the diagnosis was confirmed histologically. Because PXE is a heterogeneous heritable disorder, the family was evaluated for this condition. Since the patient's mother and brother showed some manifestations of PXE, autosomal dominant inheritance is the most likely inheritance pattern in this family.

Protracted arthritis of familial Mediterranean fever (an unusual complication).

An unusual case of familial Mediterranean fever and vasculitis in which the patient developed amyloidosis and had protracted arthritis persisting for years is presented. The long-standing arthritis did not respond to corticosteroid and colchicine therapy, but an excellent response to synovectomy was achieved.

Low-dose erythropoietin is effective and safe in children on continuous ambulatory peritoneal dialysis.

Hypertension is one of the most important complications of erythropoietin (rHuEPO) therapy in dialysis patients. In this study, the effect of two different dosage regiments of subcutaneous rHuEPO on blood pressure [BP] was evaluated in 20 anemic children on continuous ambulatory peritoneal dialysis (CAPD). Patients were randomized to receive rHuEPO 50 U/kg, either once a week (group 1, 50 U/kg per week) or three times a week (group 2, 150 U/kg per week). At the beginning of the study, 8 patients in group 1 and 8 patients in group 2 were on antihypertensive therapy. In group 1, the hematocrit increased gradually and significantly from 18.98% +/- 1.79% to 30.1% +/- 1.62% after 6 months, while in group 2 it rapidly increased from 19.53% +/- 1.86% to 32.4% +/- 1.11% after 3 months. A significant increase in the mean arterial BP was observed in group 2. Antihypertensive therapy had to be increased in all of the 8 previously hypertensive patients and had to be initiated in 1 of the 2 originally normotensive patients in the same group. None of the patients in group 1 required a change in antihypertensive medication. We conclude that during treatment with rHuEPO pre-existing hypertension and the dose of rHuEPO are the most important risk factors for the development or worsening of hypertension in children on CAPD, and gradual elevation of hematocrit by low-dose rHuEPO avoids the development of severe hypertension.

Whole-body vibration exposure: a comprehensive field study.

A comprehensive field study investigated whole-body vibration exposure levels experienced by the train operators of a large metropolitan subway system. The purposes of the study were to measure mechanical vibrations transmitted to the seated train operators, to calculate daily whole-body vibration exposure levels, and to compare these levels with maximum acceptable exposure levels recommended by the international standard on whole-body vibration (ISO 2631). The study also sought to identify factors that may influence mechanical vibrations transmitted to the operators and quantify their effects on the measured vibration levels. The study was carried out by dividing the subway system into subway lines, each line into southbound and northbound directions, and each direction into station-to-station observations. Triaxial measurements were made on all subway lines and for all car types used in the system. For each line, at least two round trips of data were collected. Time-weighted averages of the two sets of data were used for final presentation. A total of 48 round trips were made and more than 100 hours of vibration data was collected and analyzed. All phases of the study were carried out in accordance with the procedures outlined in ISO 2631. It was determined that 6 out of 20 subway lines had vibration levels higher than daily exposure limits recommended by ISO 2631. It was also determined that train speed was the most significant factor influencing vibration exposure levels.

Flow of particles along a deformable tube.

Slow viscous flow of rigid particles along a deformable tube of comparable diameter is considered as a possible model for some biological flows. Lubrication theory is assumed to be valid in the fluid region. The cylindrical tube is considered to be a thin elastic shell undergoing small deflections. The mean velocity of the flow is assumed to be maintained at a constant value by the application of a pressure difference over some length including the particle, or by an external force acting directly on the particle. Numerical results are obtained for the force required to maintain the motion and for the distribution of fluid pressure and thickness along the tube as a function of the diameter ratio, dimensionless velocity parameter and the shape of the particle. Effect of the bending resistance of the tube on the flow is also discussed.