A 2-year prospective densitometric study on the influence of Fok-I gene polymorphism in young patients with thalassaemia major.

UNLABELLED: This study is to estimate the degree of genetic contribution of Fok-I gene polymorphism of Vitamin D receptor to bone mass in patients with thalassaemia. Results indicate a protective role of the f allele of the Fok-I gene polymorphism when found in homozygosity on bone mineral density of young thalassemic patients. INTRODUCTION: The purpose of this study is to estimate prospectively the degree of genetic contribution of Fok-I gene polymorphism of vitamin D receptor (VDR) to the evolution of bone mass in patients with beta-thalassemia major (b-TH). METHODS: Sixty-four children and young adults (33 males and 31 females) with mean decimal age of 23.20 ± 5.41 (range 9.25-32.41 years) were recruited in this study. All patients were genotyping for Fok-I gene polymorphism and were assessed with dual energy X-ray absorptiometry (DXA) at baseline and 2 years after. Z-scores were calculated based on normal age and sex matched Caucasian population. Metabolites of vitamin D, intact PTH, total calcium, inorganic phosphorous, and alkaline phosphatase were measured at the serum pre-transfusion. RESULTS: A moderate proportion of patients had decreased DXA Z-scores (Z-score ≤-2) predominately in total hip (31 %) and secondary in lumbar spine (15.6 %). Patients being homozygous for the f allele had apparently higher BMD Z-scores compared with those carrying the F allele in homo- or heterozygosity, however, with a difference that did not reached significance. Interestingly enough, a significant deterioration in BMD Z-scores measured at femur (FF: P = 0.004 Ff: P < 0.001, ff: P = 0.024) and total hip (FF: P = 0.022, Ff: P = 0.005) was recorded for all type of genotypes, except for ff genotype and with regard to the total hip DXA values. An increased prevalence of serum 25(OH)D3 deficiency (59.4 %) and 25(OH)D3 borderline (12.5 %) was recorded. CONCLUSION: Our study indicates a protective role of the f allele of the Fok-I gene polymorphism when found in homozygosity on bone mineral density of young patients with b-TM.

Comparative study of dual energy X-ray absorptiometry and quantitative ultrasonography with the use of biochemical markers of bone turnover in boys with haemophilia.

Our aim was to evaluate bone status in boys with haemophilia using dual energy X-ray absorptiometry (DXA) and quantitative ultraSonography (QUS), and in addition, to compare these two methods with the use of biochemical markers of bone turnover. Twenty-six boys with a mean decimal age of 12.08 ± 4.44 years were included in the study which included a DXA scan at lumbar spine and radial, as well as tibial QUS. Serum levels of soluble receptor activator of nuclear factor κB ligand (sRANK-L), osteoprotegerin (OPG) and osteocalcin (OC) were measured and joint evaluation was performed using the Hemophilia Joint Health Score (HJHS). With regard to the study results, only 2 of 26 patients (7.7%) had bone mineral density (BMD) Z-scores < -2, and 4 patients (15.4%) had BMD Z-scores between -1 and -2. Only one patient had radial and other two had tibial QUS Z-scores < -2. No agreement was recorded between QUS and DXA in identifying patients at risk for osteoporosis (k = 0.275, P = 0.063). Haemophiliacs had significantly higher serum levels of sRANK-L (21.04 ± 4.78 vs. 18.58 ± 2.28 ng mL(-1), P = 0.038) and of OC (5.35 ± 2.29 vs. 3.09 ± 0.61 ng mL(-1), P = 0.002) and significantly decreased levels of OPG (15.78 ± 2.53 vs. 23.79 ± 4.39 pg mL(-1), P < 0.001) compared with controls. QUS Z-scores at tibia significantly correlated with HJH Scores (r = -0.450, P = 0.040), whereas lumbar BMD Z-scores significantly correlated with body mass index Z-scores (r = 0.500, P = 0.009). More studies are warranted to identify the most accurate densitometric method for assessing bone status in haemophiliacs.

Gastrostomy as a Preemptive Measure after Pancreatoduodenectomy against Delayed Gastric Emptying: A Small Case Series and a Review of the Literature.

Delayed gastric emptying (DGE) is a common (20-30%) postoperative complication following pancreatoduodenectomy (PD) (Parmar et al., 2013). Various causes and preemptive measures have been suggested to decrease the occurrence of DGE. We added a simple step in the procedure of 26 consecutive pancreatic head resections, which seems to alleviate DGE and has never been highlighted before.

A patient with Lemierre syndrome.

Lemierre syndrome, also known as postanginal sepsis, is a severe complication of an acute oropharyngeal infection that results in septic thrombophlebitis of the ipsilateral internal jugular vein with subsequent septicemia, often complicated by metastatic infections (Syed et al., Laryngoscope 117:1605-1610, 2007). We present the case of a previously healthy 12-year-old boy with Lemierre syndrome, caused by streptococci (Abiotrophia defectiva), complicating a subcutaneous neck abscess. The patient had metastatic sequelae, was treated with antibiotics (clindamycin and vancomycin) and low molecular weight heparin, and had an uneventful outcome.

Growth hormone treatment in short children with beta-thalassemia major.

The effect of one year recombinant human growth hormone (rhGH) treatment on growth rate and bone age was studied in ten short prepubertal children with beta-thalassemia major (age range 7.10-12.03 yr) with normal GH response to provocative stimuli. rhGH was given subcutaneously every day in a dose of 28 IU/m2/week. In the 10 children who completed 12 months of treatment the growth velocity increased from 4.22+/-0.81 cm/yr (-1.38+/-0.80 SDS for CA) to 7.61+/-1.16 cm/yr (+2.27+/-1.64 SDS for CA). IGF-I was low before treatment, 138.3 +/-38.9 ng/ml, and rose significantly to 232.2+/-122.1, 243.2+/-98.4 and 227.5+/-86.2 at 3, 6 and 12 months post-treatment, respectively (p<0.01). Bone maturation was accelerated in proportion to the increase in chronological age. The mean pre-treatment bone age in the ten children was 8.20+/-1.97 and increased to 9.55+/-1.80 yr after one year of treatment. Our data demonstrate that GH treatment of thalassemic children with normal GH reserve and low serum IGF-I concentrations with supraphysiological doses of rhGH for one year can cause a significant increase in serum IGF-I levels and growth velocity, but it remains to be elucidated whether long-term administration will affect the final height.

Defining overweight and obesity among Greek children living in Thessaloniki: International versus local reference standards.

BACKGROUND: Body Mass Index (BMI) offers a simple and reasonable measure of obesity that, with the use of the appropriate reference, can help in the early detection of children with weight problems. Our aim was to compare the two most commonly used international BMI references and the national Greek BMI reference in identifying Greek children being overweight and obese. METHODS: A group of 1557 children (820 girls and 737 boys, mean age: 11.42 ± 3.51 years) were studied. Weight and height was measured using standard methods, and BMI was calculated. Overweight and obesity were determined using the International Obesity Task Force (IOTF) standards, the Centers for Disease Control and Prevention (CDC) BMI-forage curves and the most recent Greek BMI-for-age curves. RESULTS: RESULTS showed that the IOTF's cut-off limits identifies a significantly higher prevalence of overweight (22.4%) compared with both the CDC's (11.8%, p=0.03) and the Greek's (7.4%, p=0.002) cut-off limits. However, the prevalence of obesity was generally increased when it was determined using the CDC's cut-off limits (13.9%) compared to the prevalence calculated with both the IOTF's (6.5%, p=0.05) and the Greek's (6.9%, n.s.) cut off limits. CONCLUSIONS: The use of the national Greek reference standards for BMI underestimates the true prevalence of overweight and obesity. On the contrary, both the IOTF and the CDC standards, although independently, detect an increased number of overweight and obese children and thus they should be adopted in the clinical practice for an earlier identification and a timelier intervention.

Use of propranolol in infantile haemangiomas: report of five cases and review of the literature.

Infantile haemangiomas are common benign tumours that do not require treatment unless they cause significant functional impairment or disfigurement. We report our experience with the off-label use of propranolol in 5 children with haemangiomas and review the relevant literature.

Transfusion-related acute lung injury management in a pediatric intensive care unit.

Transfusion-related acute lung injury (TRALI) constitutes a life threatening complication of blood transfusion. In severe TRALI cases supportive care with mechanical ventilation in intensive care unit is needed. We present two severe TRALI cases caused by leukocyte depleted, ABO compatible, packed red blood cell transfusions, coming from multiparous women donors. In the first case diagnosis was based on clinical findings and established by the identification of leukocyte antibodies in donor's unit and recipient's serum and she deal with invasive mechanical ventilation. In the second case, diagnosis was based on clinical criteria and chest radiograph findings and non-invasive mechanical ventilation was used. Both cases were treated in a Pediatric Intensive Care Unit and they had a favorable outcome.

Successful treatment of a spontaneous haemothorax with recombinant factor VIIa in a haemophilic child with inhibitors.

Haemophilia A is an X-linked disorder caused by a deficiency of factor VIII. Haemorrhage in various sites may occur spontaneously or secondary to trauma depending on the severity of the deficiency. Common manifestations include haemarthrosis, epistaxis, gastrointestinal haemorrhage and haematuria. Spontaneous haemothorax has rarely been reported both in children and adults1,2. We report the case of a haemophiliac child presenting with spontaneous haemothorax due to the rarity of this clinical presentation in order to raise the awareness among clinicians.

Intragenic interspecific complementation of glucose 6-phosphate dehydrogenase in human-hamster cell hybrids.

A new variant of human glucose 6-phosphate dehydrogenase (G6PD), provisionally designated G6PD Harilaou, was observed in a Greek boy affected by severe hemolytic anemia. G6PD Harilaou was associated with very severe deficiency of enzyme activity, which measured about 1% of normal in the patient's fibroblasts. By fusion of Harilaou fibroblasts with a similarly enzyme-deficient mutant CHO cell line, we have isolated a hybrid cell line that has a G6PD activity 5-10 times higher than either of the parental cells. By electrophoretic analysis we show that most of this activity is associated with a hybrid dimeric G6PD molecule consisting of one hamster and one human subunit. We suggest that this heterologous quasi-interallelic complementation is effected by a catalytically abnormal hamster subunit stabilizing a catalytically abnormal and unstable Harilaou subunit. This approach may be useful for the study of dimer formation and stability in human G6PD.

Long term audiological evaluation of beta-thalassemic patients.

OBJECTIVE: The objective of this study was to identify the incidence and to monitor the progression of hearing loss in children and young adults with beta-thalassemia major. METHODS: One hundred and four (104) patients aged 6-35 years (mean 17,2 years) participated in the study. All patients were on a regular transfusion-chelation program maintaining a mean hemoglobin level of 9.5 gr/dl. Subjects were receiving desferrioxamine (DFO) chelation treatment with a mean daily dose of 50-60 mg/kg, 5-6 days a week during the first six years of the study, which was then reduced to 40-50 mg/kg for the following eight years. Patients were followed for 8-14 years. RESULTS: Overall, 21 out of 104 patients (20.2%) presented with high frequency sensorineural hearing loss (SNHL), either unilateral or bilateral. No ototoxic factor, other than DFO, was present in any of the patients. Patients with SNHL presented with relatively lower serum ferritin levels than those with normal hearing, however, no statistically significant difference was observed. Subjects with SNHL were submitted to DFO reduction or temporary withdrawal. Following intervention, 7 out of 21 affected patients recovered, 10 remained stable and 4 demonstrated aggravation. CONCLUSION: The findings are indicative of DFO's contributing role in the development of hearing impairment. Regular audiologic evaluation is imperative in all thalassemic patients so that early changes may be recognized and treatment may be judiciously adjusted in order to prevent or reverse hearing impairment.

Iron-related disturbances of cell-mediated immunity in multitransfused children with thalassemia major.

Immunological abnormalities have been observed in many haemophiliacs receiving clotting factor concentrates. To determine whether similar changes also occur after repeated blood transfusions we estimated T cell subsets and cutaneous delayed hypersensitivity (CDH) in 50 multitransfused children with beta-thalassemia major (beta-TM). All patients were also tested for anti-HTLV-III/LAV antibodies. A diminished percentage of T lymphocytes (E-rosettes, T3+), and T4+ cells and a low T4/T8 ratio was found in patients as compared to age and sex matched controls (P less than 0.001). Negative CDH tests to specific antigens (Multi-test) were also found in a significantly larger proportion of beta-TM children (P less than 0.01). Antibodies against HTLV-III/LAV were negative in all patients. Decreased T4/T8 ratio in beta-TM children was primarily due to a reduction of T4+ cells and was inversely correlated to the patients' age, number of units of transfused blood (P less than 0.05) and especially to ferritin serum levels and annual iron balance (P less than 0.001). These findings indicate that immunological abnormalities in beta-TM patients appear to be acquired, transfusion-associated and related to iron load which depends on the appropriate chelation therapy.

Clinical and haematological consequences of recurrent G6PD mutations and a single new mutation causing chronic nonspherocytic haemolytic anaemia.

We have determined the causative mutation in 12 cases of glucose-6-phosphate dehydrogenase deficiency associated with chronic non-spherocytic haemolytic anaemia. In 11 of them the mutation we found had been previously reported in unrelated individuals. These mutations comprise seven different missense mutations and a 24 base pair deletion. G6PD Nara, previously found in a Japanese boy. Repeated findings of the same mutations suggests that a limited number of amino acid changes can produce the CNSHA phenotype and be compatible with normal development. The one new mutation we have found, G6PD Serres, is 1082 C-->T causing a 361 Ala-->Val substitution in the dimer interface where most other severe G6PD mutations are found. Now that several patients with the same mutation have been reported we can compare the resulting clinical phenotypes. For each mutation we find a reasonably consistent clinical picture, ranging from mild (G6PD Clinic) through moderate (G6PD Nashville) to severe (G6PD Beverly Hills and G6PD Nara).