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C Kattamis

Publications and source records attributed to C Kattamis.

At least 37 records · Page 2Linked to original sources
PubMed1998

Growth and management of short stature in thalassaemia major.

UNLABELLED: With modern treatment and longer survival of patients with homozygous beta-thalassaemia endocrine dysfunction assumes greater importance. Short stature, delayed puberty and hypogonadism are major problems in both adolescent and adult patients. Growth failure has been attributed to GH deficiency (hypothalamic or pituitary), hypothyroidism, delayed sexual maturation, hypogonadism, diabetes mellitus, zinc deficit, low Hb levels, bone disorders and desferrioxamine toxicity. The present report concentrates on the incidence of short stature among children aged 7-8 years (n = 50) and young adults aged 20-29 years (n = 93) with blood transfusion dependent homozygous beta-thalassaemia appropriately treated who have entered and completed puberty spontaneously (n = 45) or with treatment (n = 48) and have attained final height. It also concentrates on the role of GH in the growth retardation of 65 blood transfusion dependent thalassaemia major patients, their GH response to provocative stimulation, the effect of rhGH therapy on growth and final height in 13 patients who had GH deficiency and the effect of long acting androgens on growth and final height of 11 short boys with thalassaemia major, delayed puberty and normal GH secretion. CONCLUSION: 8% of young boys with thalassaemia major aged 7-8 years have short stature. 12% of the older boys and 15% of the older girls without endocrinopathies had height < 3rd percentile. This incidence was 29% when endocrinopathies were present. GH deficiency is rare among short blood transfusion dependent thalassaemia major patients (20%) and seems to play a limited role in the etiology of growth retardation. One year treatment with rhGH improved growth rate and predicted height without causing serious metabolic problems. Long term administration of rhGH is also safe and promising. Patients with thalassaemia major can achieve acceptable final heights but below their target heights with rhGH therapy. Low dose long acting sex steroid treatment in boys with delayed puberty, delayed bone age and without GH deficiency for a year or more is safe and can produce similar results to those obtained with rhGH therapy.

Adolescent↗
PubMed1998

Glucose disturbances and regulation with glibenclamide in thalassemia.

Specific laboratory and clinical characteristics indicate that the pathogenesis of diabetes in patients with thalassemia resembles the pathogenesis of maturity-onset diabetes (type II). Thus oral hypoglycemic agents may be used to regulate blood glucose levels by induction of insulin secretion and reduction of insulin resistance. The efficacy of glibenclamide administration in the management of glucose disturbances was evaluated in 33 patients with thalassemia, aged 12-30 years (mean 17.4 +/- 3.7), in whom diet and exercise failed to regulate hyperglycemia. The results were compared to 30 thalassemic patients (mean age 18.4 +/- 4.8 yr), who followed only diet and exercise. Improvement of OGTT was observed in 73% of the treated patients versus 43% of the control group for a mean period of 59 months. Deterioration of OGTT occurred more rapidly (33.7 +/- 26.1 vs 40.7 +/- 34.5 mos), and in more patients of the untreated group (57%) than in treated patients (27%). Among treated patients, effectiveness of oral hypoglycemic agents lasted longer in patients with diabetic (64.1 +/- 40.3 mos) than in patients with impaired curves (54.2 +/- 31 mos).

Adolescent↗
PubMed1997

Effective detection of active HCV infection: HCV RNA carrier state in a context free of hepatitis symptoms.

HCV immunological assays have limited specificity due to considerable variability of genomic coding sequences. Accordingly, PCR RNA detection also shows variable incidence of HCV in a non-A, non-B (NANB) hepatitis context. We used in-house designed nested PCR applying primers from the 5' untranslated region in 150 thalassemic patients classified in four groups according to anti-HCV screening and glutamic-pyruvate transaminase (GPT) levels. Group A: anti-HCV+/high GPT levels; group B: anti-HCV+/normal GPT levels; group C: anti-HCV(-)+high GPT levels; group D: anti-HCV(-)+normal GPT levels. Viral incidence and concentration, both high in group A, decreased towards group D. Group C RNA incidence was unexpectedly high and, moreover, one control case proved HCV-RNA+. Compared with the Amplicor kit or primers were considerably more sensitive.

Adolescent↗
PubMed1997

Corticosteroid treatment of erythema multiforme major (Stevens-Johnson syndrome) in children.

UNLABELLED: The effectiveness of systemic corticosteroids in erythema multiforme major (EMM) is controversial. We therefore evaluated the efficacy of corticosteroids in the treatment of EMM in a prospective study of 16 children with EMM admitted to our department within 3 days from the onset of rash. Ten patients (group A) received bolus infusions of methylprednisolone (4 mg/kg/day) while six had only supportive treatment (group B). The early use of corticosteroids compared to supportive treatment resulted in: (1) significant reduction of the period of fever (4.0 +/- 1.9 vs 9.5 +/- 4.2 days P = 0.01); (2) reduction of the period of acute eruption (7.0 +/- 3.3 versus 9.8 +/- 3.0 days P = 0.08); and (3) milder signs of prostration. Complications were minimal in both groups. CONCLUSION: The early and short course of corticosteroids favourably influences the course of erythema multiforme major in children.

Adolescent↗
PubMed1997

Characterization of more than 85% of cystic fibrosis alleles in the Greek population, including five novel mutations.

To completely characterize the spectrum of mutations in the cystic fibrosis transmembrane conductance regulator gene in Greek cystic fibrosis (CF) patients, we screened 500 CF chromosomes by denaturing gradient gel electrophoresis followed by direct sequencing. We identified 48 mutations, accounting for 85.6% of CF chromosomes. They included eight novel mutations, three of which we have described before and five (E822X, Y247X, 2752-26A-->G, 3152delT, and 2751 + T-->A), which are described in this report. The detection of such a high proportion of Greek CF mutations is important for improving prenatal and genetic diagnosis of CF in Greece.

Adult↗
PubMed1997

Prenatal diagnosis of the thalassaemia syndromes by rapid DNA analytical methods.

Prenatal diagnostic strategies applied today are based mainly on polymerase chain reaction (PCR) analytical protocols. In Greece a wide range of mutations underlie the thalassaemic haemoglobinopathies, and consequently a variety of PCR-based methods are required to facilitate diagnosis of all potential abnormal genotypes. PCR protocols include those which are relatively simple and others that are technically challenging, but very few have been designed for high through-put clinical diagnostics. Over a period of 18 months we carried out prenatal diagnosis of 147 pregnancies (150 fetal samples) at risk for a wide range of haemoglobinopathies. This involved the precise characterization of parental genotypes and the subsequent analysis of fetal DNA samples. In this series, 18 different mutations in the alpha- or beta-globin clusters were identified. For the characterization of these mutations, five PCR-based protocols were selected: denaturing gradient gel electrophoresis (DGGE), amplification refractory mutation system (ARMS) PCR, restriction endonuclease analysis of PCR fragments, oligonucleotide hybridization and 'gap' PCR for detection of deletions. To avoid spurious diagnosis due to contamination of fetal samples, two additional methods were used to genotype polymorphic variable nucleotide tandem repeat (VNTR) regions of the genome in parental and fetal samples. Through analysis of the results we assess the advantages and drawbacks of the selected PCR-based protocols for providing routine clinical diagnostics.

Alleles↗
PubMed1996

The interaction of alpha zero thalassaemia with Hb Icaria: three unusual cases of haemoglobinopathy H.

The clinical, haematological, biosynthetic and molecular data of three Greek haemoglobin H (HbH) disease patients with a distinctive clinical phenotype are described. During infancy all three patients had unusually severe clinical manifestations for HbH disease, with anaemia necessitating blood transfusions, signs of bone changes, growth impairment, and splenomegaly. Molecular analysis identified a rare alpha-thalassaemia genotype (--Med/ alpha Ic alpha). Splenectomy resulted in marked amelioration of the clinical signs; post splenectomy all three patients preserve adequate haemoglobin levels (9-10 g/dl) with growth restored to normal. Despite the initial severe clinical phenotype in these patients, our experience indicates that splenectomy modifies the clinical course to that of mild thalassaemia intermedia. This observation should be considered carefully when giving genetic counselling to families carrying the rare Hb Icaria mutation and an alpha zero thalassaemia mutation.

Autoradiography↗
PubMed1996

The triplicated alpha-globin gene locus in beta-thalassaemia heterozygotes: clinical, haematological, biosynthetic and molecular studies.

Excess alpha-globin chains play a major role in the pathophysiology of homozygous beta-thalassaemia. In beta-thalassaemia carriers a minor effect of alpha-globin chain excess is reflected in a minimal or mild anaemia without clinical symptoms. Factors that increase alpha-chain excess in heterozygotes are expected to accentuate the severity of the clinical and haematological phenotype. We report the clinical, haematological, biosynthetic and molecular data in three beta-thalassaemia heterozygotes with the rare interaction of homozygosity for alpha-globin gene triplication, and in 17 heterozygotes with a single additional alpha-globin gene. The three patients homozygous for the alpha-globin gene locus (anti 3.7 kb arrangement) had beta(0)-thalassaemia mutations and a diagnosis of thalassaemia intermedia, preserving haemoglobin levels around 7-8 g/dl. Of the 17 beta-thalassaemia heterozygotes (six children and 11 adults), 16 had severe beta-thalassaemia mutations interacting with an additional alpha-globin gene (13 with alpha alpha alpha anti-3.7 and four with alpha alpha alpha anti-4.2). Compared to simple beta-thalassaemia heterozygotes, they had lower haemoglobin levels and red cell indices, but higher alpha/beta biosynthesis, HbF levels and reticulocytes. Our results suggest that homozygous alpha-gene triplication interacts with a severe beta-thalassaemia mutation to cause an alpha-chain excess equivalent to that observed in homozygous beta-thalassaemia intermedia. In heterozygotes for severe beta-thalassaemia mutations with one additional alpha-globin gene, the alpha-chain excess causes a more pronounced degree of anaemia than is usually seen in simple beta-thalassaemia heterozygotes.

Adult↗
PubMed1996

The impact of neocyte transfusion in the management of thalassaemia.

Transfusional iron overload leading to cardiopathy and other severe complications continues to be a major problem in chronically transfused homozygous beta-thalassaemia patients. It is well known that young red cells (neocytes) survive longer after transfusion and therefore may contribute to the extension of the intervals between transfusions. We evaluated the impact of neocytes in the total annual blood requirements and consequently the transfusional iron load in 18 thalassaemia patients. A two-period study comparing transfusions of standard red cells versus neocytes in the same group of patients was performed. Neocytes were harvested by density separation using the Neocel System. The method of preparation was simple with relatively low costs and required no special equipment. There was a significant difference (p < 0.005) in PK and MCV values of the neocyte and older red cell (gerocyte) fractions indicating that a good separation of the two populations was achieved. All patients had a reduction in blood requirements during the neocyte period. The total annually transfused red blood cells and concomitant iron blood load were significantly reduced (p < 0.001) by 20.2 +/- 9.1%. However, the response was variable. Seven of the 18 patients had a large reduction in blood consumption (24.8-34.8%), 9 others ranged between 10.7 and 21.6%, and in 2 the reduction was less than 10%. This reduction in blood requirements and in the transfused iron may change the chelation index resulting in more efficient iron chelation therapy and perhaps reduce the cost of the haemochromatosis therapy on a long-term basis. We conclude that the use of neocyte therapy using this system can benefit the majority of chronically transfused patients by reducing transfusional iron overload and related complications and may lead to a much better quality of life.

Adolescent↗
PubMed1996

Gaucher disease: four families with previously undescribed mutations.

We describe four families with patients with type I Gaucher disease exhibiting previously undescribed mutations of the glucocerebrosidase gene. We found Cherokee Indian woman to have a G-->C substitution in cDNA nucleotide 354, predicting a lysine-->aspargine substitution in amino acid 79 of the processed protein. In a Greek family, we found an allele with a C-->T substitution in nucleotide 475 giving rise to an arginine-->tryptophan substitution at amino acid 120. In another non-Jewish European patient, we identified a C-->T substitution in nucleotide 1223, predicting a threonine-->methionine mutation in amino acid 369. We found two non-Jewish European children to have a C-->T mutation at nucleotide 1357, predicting termination at codon 414. Although siblings carry the same two glucocerebrosidase mutations, in these families as in others we noted considerable differences in severity of clinical manifestations. Finding the reason for these differences is an important goal in the study of Gaucher disease.

Adult↗
PubMed1995

Mutation analysis of ten exons of the CFTR gene in Greek cystic fibrosis patients: characterization of 74.5% of CF alleles including one novel mutation.

To initiate the complete characterization of mutations in the CFTR gene in Greek cystic fibrosis (CF) patients, we screened 184 patients for six relatively common mutations (delta F 508, G542X, G551D, 621 + 1 G-->T, N1303K, W1282X) using allele-specific hybridization and, in addition, analyzed exons 4, 5, 7, 8, 10, 11, 17b, 19, 20 and 21 using the method of denaturing gradient gel electrophoresis (DGGE). Six mutations accounted for 65.9% of the CF alleles in Greek patients, of which the delta F 508 mutation had a frequency of 52.7%. A further 15 previously described mutations accounted for another 8.3% CF alleles and one previously undescribed mutation (3272-4A-->G) was found in one chromosome. The W1282X mutation was not detected at all. Thus, so far, we have identified 21 mutations in the CFTR gene in Greek CF patients, accounting for 74.5% of the CF alleles.

Alleles↗
PubMed1995

Assessment of liver iron overload by T2-quantitative magnetic resonance imaging: correlation of T2-QMRI measurements with serum ferritin concentration and histologic grading of siderosis.

PURPOSE: To correlate hepatic 1/T2 values obtained by means of a T2-Quantitative MRI (T2-QMRI) technique with three widely applied methods for the evaluation of hemosiderosis, i.e., (a) liver iron concentrations (LFeC) (b) serum ferritin (SF), and (c) histologic grading of siderosis. The impact of coexisting hepatitis was also considered. T2-QMRI measurements were compared with signal intensity (SI) ratio measurements on conventional SE images. MATERIALS AND METHODS: Liver T2 relaxation times were calculated in 40 thalassemic patients, on a 0.5 T magnetic resonance imaging system using a multiple spin-echo sequence with parameters: TR = 2500 ms, TE = 12 ms in 20 symmetrically repeatable echoes. RESULTS: (a) 1/T2 values were well correlated (r = 0.97) with liver iron concentrations, which ranged from 2.32 to 18.0 mg/g dry weight (normal < 1.6 mg/g). (b) 1/T2 values were also correlated with serum ferritin levels (r = 0.84). At various 1/T2 values, serum ferritin levels were higher for the anti-HCV(+) patients than the anti-HCV(-) ones. (c) T2 values corresponding to successive grades of siderosis presented statistically significant differences. (d) SI ratio measurement assigned less statistically significant results, as compared to T2 values. CONCLUSION: T2-QMRI measurement of T2 relaxation time is more accurate than SI ratios in evaluating liver iron overload. It is particularly useful for hemosiderotic patients with coexisting hepatitis since, in this case, serum ferritin is not considered a reliable index of hemosiderosis.

Adult↗
PubMed1995

[Clinical evaluation of various preventive methods for non-hemolytic transfusion reactions].

A study has been carried out on the incidence of non-hemolytic transfusion reaction on a group of patients suffering from thalassemia. Of this group, the rate of reactions per patient, based on the relationship between the number of patients with non-hemolytic transfusion reactions and the total number had risen to 31.8%. 83.7% of the patients with non-hemolytic transfusion reactions did not give a positive reaction to lymphocytotoxicity. 654 patients having, or not having shown a non-hemolytic transfusion reaction received washed red cell concentrates prepared extemporaneously. This process allowed the rate of reaction per patient to drop to 3.9%. The transfusion of deleucocytated red cell concentrates by filtration, carried out on a group of 188 patients, made the rate of reaction per patient drop to 2.8%. As regards to rate reaction per patient, there is no significant difference statistically between these two groups, however, it must be pointed out that the administration of filtered red cell concentrates, by deleucocytation, notably improves the incidence of a feverish reaction, while the administration of washed red cell concentrates has an important impact on allergic reactions. Interestingly, in solution, the washed red cell concentrates have the added advantage of having only very small quantities of free iron or vasoactive proteic derivatives. The new four bag system, now allows us to collect, separate and wash in a closed circuit. Compared to the traditional method this system has the advantage of assuring greater efficiency and security. In conclusion, for the first time, the administration of washed red cell concentrates on patients who receive regular transfusions, may represent a good procedure, combined or not with deleucocytation by filtration, as to prevent the occurrence of non-hemolytic reactions.

Case-Control Studies↗