Thrombin activatable fibrinolysis inhibitor : its role in slow coronary flow.

BACKGROUND: The slow coronary flow (SCF) phenomenon is characterized by slow progression of angiographic contrast medium in the coronary arteries in the absence of stenosis in the epicardial vessels. The pathophysiological mechanisms of SCF phenomenon remain uncertain. Several hypotheses, however, have been suggested for SCF phenomenon, including an early form of atherosclerosis, small vessel dysfunction, dilatation of coronary vessels, imbalance between vasoconstrictor and vasodilatory factors, platelet function disorder, and inflammation. Atherosclerosis and inflammation are the most accepted mechanisms for the pathogenesis of SCF. Thrombin activatable fibrinolysis inhibitor (TAFI) was described as a new inhibitor of fibrinolysis recently and plays an important role in coagulation and fibrinolysis. In previous studies, the role of TAFI was associated with inflammation and evolution of atherosclerosis in coronary artery disease. There are no data available about TAFI levels in patients with SCF phenomenon investigated by angiography. Our goal was to evaluate TAFI antigen (Ag) levels in patients with SCF and to determine the association of the TAFI Ag level with traditional cardiovascular risk factors in our study. METHODS: The study group constituted 41 patients with angiographically confirmed SCF and 46 patients with normal coronary flow as the control group. The TAFI Ag levels of each patient were determined. RESULTS: Between the control and study group, a statistical difference in the levels of TAFI Ag (p < 0.05) was observed. The TAFI Ag level was significantly higher in the SCF group than the control group (132.21 ± 21.14 versus 122.15 ± 21.59). CONCLUSION: We have demonstrated that TAFI might be a risk factor for the development of SCF independently of conventional cardiovascular risk factors. In addition, TAFI Ag levels were positively correlated with C-reactive protein (CRP) known as an acute phase reactant. Our findings support the reports of previous studies that increased TAFI levels may be associated with inflammation. Further large studies are required to evaluate the importance of TAFI antigen levels in relation to the development of SCF.

Prediction of outcome in isolated methylmalonic acidurias: combined use of clinical and biochemical parameters.

Objectives Isolated methylmalonic acidurias (MMAurias) are caused by deficiency of methylmalonyl-CoA mutase or by defects in the synthesis of its cofactor 5'-deoxyadenosylcobalamin. The aim of this study was to evaluate which parameters best predicted the long-term outcome. Methods Standardized questionnaires were sent to 20 European metabolic centres asking for age at diagnosis, birth decade, diagnostic work-up, cobalamin responsiveness, enzymatic subgroup (mut(0), mut(-), cblA, cblB) and different aspects of long-term outcome. Results 273 patients were included. Neonatal onset of the disease was associated with increased mortality rate, high frequency of developmental delay, and severe handicap. Cobalamin non-responsive patients with neonatal onset born in the 1970s and 1980s had a particularly poor outcome. A more favourable outcome was found in patients with late onset of symptoms, especially when cobalamin responsive or classified as mut(-). Prevention of neonatal crises in pre-symptomatically diagnosed newborns was identified as a protective factor concerning handicap. Chronic renal failure manifested earlier in mut(0) patients than in other enzymatic subgroups. Conclusion Outcome in MMAurias is best predicted by the enzymatic subgroup, cobalamin responsiveness, age at onset and birth decade. The prognosis is still unfavourable in patients with neonatal metabolic crises and non-responsiveness to cobalamin, in particular mut(0) patients.

Diagnostic work-up and management of patients with isolated methylmalonic acidurias in European metabolic centres.

The long-term outcome of patients with methylmalonic aciduria (MMA) is still uncertain due to a high frequency of complications such as chronic renal failure and metabolic stroke. The understanding of this disease is hampered by a huge variation in the management of these patients. The major aim of this study was to evaluate the current practice in different European metabolic centres. A standardized questionnaire was sent to 20 metabolic centres asking for standard procedures for confirmation of diagnosis, testing cobalamin responsiveness, dietary treatment, pharmacotherapy, and biochemical and clinical monitoring. Sixteen of 20 metabolic centres (80%) returned questionnaires on 183 patients: 89 of the patients were classified as mut(0), 36 as mut(-), 13 as cblA, 7 as cblB, and 38 as cblA/B. (1) Confirmation of diagnosis: All centres investigate enzyme activity by propionate fixation in fibroblasts; six centres also perform mutation analysis. (2) Cobalamin response: Ten centres follow standardized protocols showing large variations. A reliable exclusion of nonspecific effects has not yet been achieved by these protocols. (3) Long-term treatment: In cobalamin-responsive patients, most centres use hydroxocobalamin (1-14 mg/week i.m. or 5-20 mg/week orally), while two centres use cyanocobalamin. All cobalamin-nonresponsive patients and most cobalamin-responsive patients are supplemented with L: -carnitine (50-100 mg/kg per day). Fourteen centres use intestinal decontamination by antibiotic therapy. Most centres follow D-A-CH (n = 6) or Dewey (n = 4) recommendations for protein requirements. Fourteen centres regularly use precursor-free amino acid supplements. Standardized monitoring protocols are available in seven centres, again showing high variability.

Audiologic findings in children with biotinidase deficiency in Turkey.

OBJECTIVE: Biotinidase deficiency is an autosomal recessively inherited disorder characterized by neurological and cutaneous features, including sensorineural hearing loss. Although many features of the disorder are reversible following treatment with biotin, the hearing loss appears to be irreversible. In the present study, hearing status of patients with biotinidase deficiency is characterized in a Turkish population. METHODS: Subjective and objective audiologic tests were performed on 20 children with profound biotinidase deficiency. RESULTS: Sensorineural hearing loss occurs in approximately 55% of the children with biotinidase deficiency. The hearing loss varies in severity from mild to profound hearing loss. In children diagnosed immediately after birth because they had an older sibling with the disorder, statistically significant differences were found between ABR results and age of diagnosis (p<0.05). Greater prolongation in ABR latencies were observed in the late-diagnosed children compared to that in the early-diagnosed children (p<0.05). CONCLUSION: Early diagnosis is important to prevent peripheral and central hearing loss. Children with biotinidase deficiency who have hearing loss are likely at increased risk for having speech and language problems. If hearing aids do not provide sufficient amplification, cochlear implantation may be indicated in these children. Therefore, it is important to test the hearing thresholds of these children with hearing aids and evaluate their language development.

Antiannexin V autoantibody in thrombophilic Behçet's disease.

We propose that thrombosis in Behçet's syndrome may be due to disruption of the annexin V shield by antiphospholipid antibodies. Measurement of antiannexin V antibodies may be of value in confirming diagnosis and evaluating the risk of venous and arterial thrombosis in patients with Behçet's syndrome. To evaluate the efficiency of antiannexin V antibody in the formation of thrombosis, 53 male patients with Behçet's disease according to international study group criteria were involved in this study. The age range was 20-28 years (mean 23+/-3.4). All of these patients had been taking colchicum. Those taking medications that interfere with antiannexin V autoantibody levels were excluded, and serum samples were taken during the active period. Group I included 26 Behçet's patients with well-documented thrombosis, group II included 27 Behçet's patients without thrombosis, and group III was comprised of 27 healthy controls. There were no statistical differences between the mean concentrations of IgG and IgM antiannexin V autoantibodies in the three groups. The results indicate that these antibodies may not be associated with the pathogenesis of thrombotic events in patients with Behçet's syndrome.

Bone age in children with nocturnal enuresis.

It is widely believed that nocturnal enuresis is caused by a hereditary delay in maturation of the various organ systems. In this study, growth and bone age were investigated in enuretic children. There was a significant bone age lag in the enuretic group compared to the control subjects of similar age (8.15 +/- 1.56 years vs 9.45 +/- 2.17 years, p < 0.05). It has been suggested that skeletal maturation also are retarded in nocturnal enuresis; and, it may be caused by the delayed maturation in regulatory functions of the central nervous system

Analysis of heart rate variability in children with primary nocturnal enuresis.

Although nocturnal enuresis is probably the most common developmental disorder in children, the pathogenesis and management remain unclear. Autonomic dysfunction is one of the proposed mechanisms for nocturnal enuresis in children. The objective of current study was to evaluate autonomic nervous system functions in enuretic children. Twenty-four-hour ambulatory electrocardiographic recordings were obtained, and the time domain variables of HRV were calculated. The results of the present study suggest that sympathetic nervous system hyperactivity is present in enuretic children. This may explain why some enuretic children do not respond to anticholinergic medications. If these conflicting results are confirmed by large-scale clinical studies, Holter ECG examinations may be used for rational approaches in treatment of nocturnal enuresis.

Evaluation of DNA damage using the comet assay in children on long-term benzathine penicillin for secondary prophylaxis of rheumatic fever.

BACKGROUND: Benzathine penicillin is the most widely used antibiotic in the prophylaxis of children with rheumatic fever. The aim of the present study was to evaluate the DNA damage in children receiving one dose of 1.2 million units benzathine penicillin every 4 weeks over a long period to prevent recurrences of rheumatic fever. METHODS: Thirty-five children with confirmed rheumatic fever under benzathine penicillin prophylaxis were enrolled in the study and 35 healthy children with similar ages and socioeconomic backgrounds served as controls. To detect any DNA damage, the comet assay was performed on circulating lymphocytes from the study subjects. RESULTS: Damaged (limited and extensive migration) cells in children on prophylactic therapy were higher than those in controls (P<0.001). CONCLUSIONS: It has been suggested that differences in the comet scores were induced by the administration of benzathine penicillin over a long period of time and further investigations are needed to confirm this toxic effect.

Sister-chromatid exchange analysis on long-term benzathine penicillin for secondary prophylaxis of rheumatic fever.

A single intra-muscular injection of 1.2 millions units of benzathine penicillin every 4 weeks is the most widely used method for the antibiotic prophylaxis of rheumatic fever. The aim of this study is to evaluate the effect of long-term benzathine penicillin on DNA in patients with rheumatic fever. Thirty children with confirmed rheumatic fever who were on the benzathine penicillin prophylaxis were enrolled in the study, and 30 similar normal children served as a control group. To detect any DNA damage, SCE analysis were performed in circulating lymphocytes of the subjects. A statistically significant increased frequency of SCE was observed in children on the benzathine penicillin prophylaxis (no = 30, mean SCEs/cell +/- SD 7.54 +/- 1.81) as compared to a control group (no = 30, mean SCEs/cell +/- SD 5.82 +/- 1.40). It has been suggested that the difference in the SCE frequencies was induced by the administration of the benzathine penicillin for a long time, and further investigations are needed to confirm this toxic effect.

Thoracic ectopic kidney in a child: a case report.

Congenital thoracic ectopic kidney is a very rare developmental anomaly and the rarest form of all ectopic kidneys. It is usually asymptomatic and discovered incidentally on a routine chest radiography. We report a thoracic ectopic kidney in a 19-month-old boy, which initially presented as a well demarcated mass at the base of the right lung on chest x-ray. Intravenous pyelography (IVP) and thoraco-abdominal computed tomography (CT) demonstrated a normal functioning transdiaphragmatic thoracic ectopic right kidney, but technetium-99m DTPA and DMSA scintigraphy demonstrated pelvic stasis. We hereby discuss the features of congenital thoracic ectopic kidney and review the literature. Although it is extremely rare, thoracic ectopic kidney should be considered in differential diagnosis of a mass with a well demarcated superior margin in the lower part of the thorax, and renal scintigraphy must be performed even if CT and IVP results are normal.