[Show abstract][Hide abstract] ABSTRACT: The Cystic Fibrosis database includes amongst the 1893 gene mutations and polymorphisms a lot of missense mutations, the disease status of which still remains unproven. In populations with high rates of CFTR mutation heterogeneity, molecular diagnosis is difficult often causing counseling difficulties especially in cases of rare and/or novel mutations.
Approaches to counseling in cases of novel variants.
Thirty-seven novel variants (4 synonymous, 24 missense, 2 frameshift and 10 intronic substitutions) were identified and evaluated with the help of in silico tools.
In a diagnostic environment the answers have to be given within a specific timeframe, the in silico tools in combination with the phenotype offer some help but their diagnostic value is limited and cannot be used in isolation for the determination of the severity of the mutation.
Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 02/2012; 11(4):344-8. · 3.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background. Pulmonary hypertension (PH) is an often complication of severe cystic fibrosis (CF); however, data on the presence and impact of pulmonary vasculopathy in adult CF patients with milder disease, is very limited. Aim. To investigate, for the first time, the impact of systolic pulmonary arterial pressure (PASP) on maximal exercise capacity in adults with mild-to-moderate cystic fibrosis, without PH at rest. Methods. This is a Case Control study. Seventeen adults with mild-to-moderate CF, without PH at rest (cases) and 10 healthy, nonsmoking, age, and height matched controls were studied. All subjects underwent maximal cardiopulmonary exercise testing and echocardiography before and within 1 minute after stopping exercise. Results. Exercise ventilation parameters were similar in the two groups; however, cases, compared to controls, had higher postexercise PASP and decreased exercise capacity, established with lower peak work rate, peak O(2) uptake, anaerobic threshold, and peak O(2) pulse. Furthermore, the change in PASP values before and after exercise was strongly correlated to the parameters of exercise capacity among cases but not among controls. Conclusions. CF adults with mild-to-moderate disease should be screened for the presence of pulmonary vasculopathy, since the elevation of PASP during exercise might contribute to impaired exercise capacity.
[Show abstract][Hide abstract] ABSTRACT: Citrulline is a nonprotein amino acid synthesized in the small intestine. The aim of this study is to explore plasma citrulline levels in children with celiac disease (CD) and monitor the time-related changes of these levels after initiation of a gluten-free diet (GFD).
Fasting-plasma citrulline levels were determined by high-performance liquid chromatography in (i) 23 patients with CD before the institution of GFD, (ii) 20 patients with CD under treatment for more than 2 years responsive to a GFD, (iii) 10 children with gastrointestinal symptoms and normal small bowel biopsy, and (iv) 20 healthy controls. In group A, citrulline levels were also measured after 1, 3, 6, and 12 months on a GFD.
Mean plasma citrulline levels were lower in untreated patients with CD (24.5±4.9) than in patients on a GFD (31.2±6.7 μmol/l, P<0.001), patients with gastrointestinal symptoms and normal intestinal mucosa (30.3±4.7 μmol/l, P<0.01), and healthy controls (32.4±7.5 μmol/l, P<0.001). In untreated patients with CD,an inverse correlation was observed between citrulline concentrations and the severity of villous atrophy (r=-0.67, P<0.01). After 1 month on a GFD, patients had significantly higher levels than before diet (P<0.05) and after 3 months on diet, levels were similar to those observed in the healthy controls.
Plasma citrulline levels are lower in celiacs reflecting small bowel involvement in this disease. After a short period on GFD, citrulline levels increased rapidly, indicating that citrulline is a sensitive marker of the positive effect of GFD on intestinal repair.
European journal of gastroenterology & hepatology 03/2011; 23(3):245-9. · 1.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to evaluate adiponectin (AD) serum concentrations in 43 stable CF patients and 27 healthy subjects and to correlate them with their nutritional status. Body Composition (Bioelectrical Impedance), visceral/subcutaneous adipose tissue (VAT-SAT) in CF patients (CT-scan at L4), insulin resistance (HOMA-IR) and AD serum concentrations (ELISA) were studied. CF patients and controls had comparable weight, height, %BF, %FFM, fasting glucose, insulin and insulin resistance. CF patients had significantly lower BMI-SDS. CF males had higher %FFM and total FFM and lower %BF and total BF than females (p<0.001). Serum AD was higher in CF patients than controls (11.53+/-5.37 vs. 9.07+/-4.41 microg/ml) and comparable between females and males. AD was lowest among young malnourished patients (8.06+/-1.85 microg/ml) and highest among young patients with normal nutrition (14.56+/-7.69 microg/ml). Patients with biliary cirrhosis had higher levels than patients with normal liver (10.52+/-5.49 vs. 14.04+/-4.52 mug/ml, p<0.05). AD correlated with %BF, %FFM, FFM (kg) (p<0.05).VAT was significantly increased in malnourished patients. AD was not affected by VAT. CONCLUSIONS: Adiponectin is higher in CF patients than healthy individuals. It is decreased in malnourished young patients and increased in patients with normal nutrition and in patients with liver disease. This may be attributed to the reduced BF and to the energy deficit inherent to the disease.
Journal of Cystic Fibrosis 06/2008; 7(3):244-51. · 2.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Niemann-Pick Disease (NPD) is a heterogeneous group of autosomal recessive disorders characterized by progressive accumulation of sphingomyelin and cholesterol in lysosomes. Six types of NPD have been described based on clinical presentation and involved organs. The primary defect in NPD types A and B is a deficiency of lysosomal acid sphingomyelinase (ASM). We present a case of a 5-year-old boy with type B NPD who had severe clinical manifestations, including heart involvement. He was first admitted to the hospital at 2 months because of vomiting, refusal to feed, lethargy, hepatomegaly and mild transaminasaemia. Liver biopsy at 12 months showed lipid accumulation and fibrosis. Investigations for lysosomal storage disorders revealed increased plasma chitotriosidase (549 nmol/h per ml, normal value 0-150). At 18 months, no detectable ASM activity was observed in cultured fibroblasts (normal range 23-226 nmol/h per mg protein) confirming NPD B. Pulmonary involvement was detected with high-resolution computerized tomography which revealed reticulonodular infiltrations and thickening of the interlobular septa. At 2 years growth retardation and kyphosis were noted. At 2.5 years he manifested neurodevelopment regression, indicating CNS involvement. Cardiac involvement (grade III mitral valve insufficiency) developed at 4 years and heart failure at 5 years. Genetic analysis revealed two mutations: a H421Y mutation that is common in Saudi Arabian and Turkish patients, and a W32X mutation, which has been found in other Mediterranean patients.
[Show abstract][Hide abstract] ABSTRACT: We report Crohn's disease in an adolescent with cystic fibrosis (CF). The patient suffered from recurrent abdominal symptoms, which were attributed to distal intestinal obstruction syndrome (DIOS) until a soft tissue inflammation at the right lumbar region and iliac crest revealed an enterosubcutaneous fistula. The diagnosis of Crohn's disease was confirmed on the basis of radiological, endoscopic and histological findings.
Journal of Cystic Fibrosis 10/2007; 6(5):366-8. · 2.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ghrelin and leptin are hormones implicated in energy balance coordination and body weight regulation. There are conflicting data regarding the levels and role of leptin while ghrelin has not been studied in CF. The aim of this study was to investigate fasting serum ghrelin and leptin levels in CF adolescents as compared to healthy controls and analyze their association with body fat.
Fourteen CF adolescents having pancreatic insufficiency and twenty healthy adolescents were enrolled in the study. Diabetic patients were excluded. In all participants' height, weight, body mass index (BMI) and body fat % (BF %) were estimated. Ghrelin and leptin levels were determined after an overnight fast.
Weight, BMI and BF% were significantly lower in CF adolescents than those of controls. Fasting leptin levels in CF were significantly higher in CF patients (p=0.030), compared to controls and significantly lower in CF males as compared to CF females (p=0.01). Fasting ghrelin levels were significantly lower in CF males as compared to male controls (p<0.001) and comparable in females.
As the overall clinical outcome of CF patients is related to the nutritional status and body weight, the role of ghrelin and leptin in these patients needs to be elucidated.
Journal of Cystic Fibrosis 08/2007; 6(4):293-6. · 2.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report here a case of pica with the aim of illustrating how a common gastrointestinal problem may be masked and treated as a psychiatric condition. A 12-year-old male was referred to our hospital for anorexia, nausea, vomiting, stool discoloration and weight loss. At 2.5 years of age, he manifested persistent iron deficiency anaemia. At 4 years, he started eating paper and was referred for psychiatric evaluation and follow-up. Six months prior to admission, he underwent psychotherapy. Upon admission, his weight, height and head circumference were 33 kg (5–10th%), 147 cm (25th%), and 53 cm (75th–95th%), respectively. He had pallor, mild finger clubbing and dry skin. The liver, spleen and other organ masses were not palpable.
European Journal of Pediatrics 07/2007; 166(6):623-4. · 1.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Partial Splenic Embolization (PSE) is a non-surgical treatment for hypersplenism. It has been reported only in a limited number of patients with Cystic Fibrosis (CF). We report a case of a female cystic fibrosis patient who developed hypersplenism at the age of 14 and underwent PSE. Long term results over a period of 14 years after the procedure are presented.
Journal of Cystic Fibrosis 06/2007; 6(3):212-4. · 2.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acute recurrent/chronic pancreatitis (CP) is a complex multigenic disease. This is a case-control study consisting of 25 Greek patients with CP and a control population of 236 healthy Greek subjects. The whole coding area and neighboring intronic regions of the three genes were screened. Seventeen of 25 patients (68%) had mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: nine compound heterozygotes with either mild or severe mutations and eight heterozygotes. Four patients (16%) carried CFTR-modulating haplotypes V470-TG11-T5 and V470-TG12-T7. All were negative for PRSS1 gene mutations, while variants c.486C/T and c.738C/T were found in nine patients each, three homozygotes for the minor alleles. Two carried SPINK1 gene mutation p.N34S, one being transheterozygote with CFTR mutation p.F1052V. The promoter variant -253T>C was found in four individuals (one homozygous for the minor allele), all four being transheterozygotes with mutations in the CFTR gene as well. Finally two carried c.272C/T in the 3' untranslated region, one being a p.N34S carrier as well. In total, 80% (20/25) of patients had a molecular defect in one or both of the CFTR and SPINK1 genes, suggesting that mutations/variants in the CFTR plus or minus mutations in the SPINK1, but not the PRSS1 gene, may confer a high risk for recurrent pancreatitis.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate the concept that pancreatic dysfunction in patients having gluten sensitivity (celiac disease [CD]) or cow's milk protein enteropathy (CMPE) may result from the lack of pancreatic enzyme stimulation in the absence or decrease of cholecystokinin (CCK) secretion caused by villous atrophy.
The following parameters were measured: plasma CCK in response to a fatty meal and human pancreatic fecal elastase in 24 patients with CD while on gluten-free diet and after gluten provocation and in 12 patients with CMPE at diagnosis and after a 6-month period of cow's milk-free diet. Intestinal mucosa morphology was examined by small bowel biopsy. Sixty-three controls having no organic gastrointestinal problems were investigated once at the time of diagnostic evaluation.
Fasting CCK, obtained at a time when patients with CD or CMPE had normal intestinal mucosa, was significantly different from postprandial and comparable to that of the control group. Fasting CCK obtained from patients with villous atrophy was also statistically different, but not significantly, from the postprandial. Fasting and postprandial plasma CCK and fecal pancreatic elastase values from patients having normal intestinal mucosa were significantly higher than those obtained from patients with villous atrophy. Significant correlation of intestinal mucosa morphology and CCK with fecal elastase concentration was documented.
Exocrine pancreatic dysfunction in individuals having villous atrophy may be the consequence of decreased CCK secretion. Cholecystokinin and pancreatic secretion is restored to normal, with intestinal mucosa regeneration.
Journal of pediatric gastroenterology and nutrition 10/2006; 43(3):307-12. · 2.18 Impact Factor