Compound Heterozygosity for Hb Adana (HBA2: c.179G>A) and the –α3.7/αα Thalassemia Deletion in Greece: Clinical Phenotype and Genetic Counseling

Hb Adana (HBA2: c.179G>A) is found worldwide but is extremely rare and carriers are asymptomatic, with red cell indices similar to α⁺-thalassemia (α⁺-thal) carriers. First line screening tests are unable to detect the unstable hemoglobin (Hb). Coinheritance with the α-thal (–α^3.7) deletion is herein presented and the challenges involving genetic counseling of couples carrying the mutations are discussed.     

TSH-secreting pituitary macroadenoma in an 11-year-old girl

Graves' disease, multinodular toxic goiter or toxic adenoma are the usual causes of hyperthyroidism in children as well as in adults. We report a case of hyperthyroidism due to TSH-secreting pituitary macroadenoma in an 11-year-old girl. The patient was admitted to the Endocrine Department for pituitary function evaluation, five months after transfrontal adenomectomy and pituitary irradiation for a macroadenoma. On admission the patient was clinically hyperthyroid and the work-up established a diagnosis of hyperthyroidism due to TSH-secreting adenoma (high levels of TSH in the face of hyperthyroidism, no TSH response to TRH stimulation, diffuse thyroid goiter without eye signs or pretibial myxedema). Of interest in this case was the fact that: (a) she is the youngest patient reported with hyperthyroidism due to a TSH-secreting macroadenoma and (b) hyperthyroidism was diagnosed after adenomectomy.     

Effect of zoledronic acid on markers of bone turnover and mineral density in osteoporotic patients with beta-thalassaemia

Osteoporosis has emerged as an important cause of morbidity in patients with thalassemia major. Studies regarding the efficacy of bisphosphonates in thalassemia-induced osteoporosis have yielded conflicting results. We performed this prospective study to evaluate the efficacy of zoledronic acid in osteoporotic patients with thalassemia major. Patients, 29, were given 1 mg zoledronic acid intravenously every 3 months for a total of four doses. Twenty age- and sex-matched healthy blood donors served as controls. Before each infusion and 3 months after the last infusion, we determined serum levels of osteoprotegerin (OPG), N-terminal cross-linking telopeptide of type I collagen (NTX), osteocalcin (OC) and insulin-like growth factor 1 (IGF-1). Bone mineral density (BMD) of the lumbar spine was measured at baseline and after the treatment’s completion. At baseline, OPG did not differ significantly between patients and controls (p=0.2), NTX were higher in patients although not significantly (p=0.139), whereas, OC levels were significantly higher and IGF-1 levels significantly lower in patients than in controls (p<0.001 and p<0.006, respectively). Zoledronic acid administration resulted in a significant decrease in NTX, OC and IGF-1 (p<0.05, p<0.001 and p<0.05, respectively) and in a significant increase in OPG and BMD (p<0.05 for both comparisons). The change in NTX, osteocalcin and IGF-1 became significant as early as 3 months after the first administration of zoledronic acid, while the change in OPG reached significance only after three infusions. Our study supports the effectiveness of bisphosphonates in the treatment of thalassemia-induced osteoporosis.     

1 alpha(OH)D3 treatment and procollagen III (PC III) studies in idiopathic myelofibrosis

Eight patients with idiopathic myelofibrosis (IMF) were treated with escalating doses (0.5 microgram/day to 4.0 micrograms/day) of 1 alpha(OH)D3 for periods up to 6 months. The treatment did not improve the disease parameters in any of the patients under study. No patient demonstrated a decrease in bone marrow fibrosis as determined by serial procollagen (PC III) serum level analysis. Although 1 alpha(OH)D3 was well tolerated at the administered doses, the therapeutic value of this treatment for IMF requires further evaluation.     

Vascular endothelial growth factor and nitric oxide serum levels in arterial hypertension

Vascular endothelial growth factor (VEGF) is a specific mitogen for endothelial cells and an inducer of the angiogenic procedure. Endothelial nitric oxide (NO) is a potent vasodilator. Because both are implicated in vascular function, it is possible that they would be significantly affected in arterial hypertension. The aim of the study was the investigation of the levels of the two substances in blood serum and their potential relation in patients with untreated essential arterial hypertension compared to healthy individuals. VEGF levels were found 129.1 +/- 135.9 pg/mL in a group of 28 untreated hypertensive patients vs. 209.0 +/- 133.3 pg/mL in a group of 28 healthy individuals (p = 0.008). Nitrites and nitrates levels (as an indirect index of calculating NO levels) were also lower in hypertensive patients than in healthy individuals (19.8 +/- 9.7 micromol/L vs. 29.6 +/- 15.9 micromol/L, p = 0.014). A positive correlation between NOx (nitrites and nitrates levels) and VEGF was found in healthy individuals (r = 0.55, p = 0.003), but there was no correlation in hypertensive patients. The significant decrease of serum VEGF and NO in arterial hypertension and the existence of a correlation between the two substances in healthy subjects that did not exist in the hypertensive patients are findings that need evaluation.     

A comparative study of three extraction protocols of DNA from nails: Potential use in the diagnosis of onychomycoses

Molecular techniques can be useful adjuncts to the diagnosis of onychomycoses. However, the nail presents difficulties in the extraction of its DNA. The comparison of three extraction protocols of DNA from nails and their ranking for possible use in the molecular diagnosis of onychomycoses are described. Extraction was performed on weighed nail clippings of equal size from positive (31) or negative (14) samples, according to the culture result. At Prot1, the extraction was performed according to Tahir and Watson, with an additional step implementing silica columns. At Prot2, the methodology proposed by the Statens Serum Institute of Copenhagen was used. At Prot3, DNA was extracted by the use of magnetic separation after homogenisation with glass beading. The evaluation parameters were DNA purity, DNA concentration, total DNA yield/g of tissue, cost and duration. The multiples of the means of medians of the first three parameters, for each protocol, were calculated. Prot3 showed the highest DNA purity. Prot2 presented the highest DNA concentration and DNA yield/g of tissue, while it was the cheapest and shortest. In total, the three protocols were graded as Prot2>Prot1>Prot3. The second method, although had a lower DNA purity, presented the higher DNA concentration and DNA yield, while its duration and cost were also favourable.     

Hemoglobin E-Saskatoon and pregnancy: report of two cases

Hemoglobin E-Saskatoon (beta22-Glu-Lys) is found worldwide but is extremely rarely. Two cases of pregnant women who carried the abnormal hemoglobin and the various problems that arise from it are reported. A discussion of the combinations with other abnormal hemoglobin is also presented.     

Detection of anti-BP180NC16a and anti-BP230 autoantibodies in blister fluid of patients with bullous pemphigoid: the first survey in Greece

Bullous pemphigoid (BP) is an acquired bullous disease with an increasing prevalence among elderly people worldwide, including in Greece. Blister formation in most patients with BP is caused by autoantibodies against structural components of the basement membrane zone of the skin, predominantly BP180NC16a and BP230 antigens on the hemidesmosome adhesion complex. Routine diagnostic methods such as histological examination and direct and indirect immunofluorescence are combined to determine diagnosis. In this study, an ELISA was used to measure levels of both anti-BP180NC16A and anti-BP230 autoantibodies in the blister fluid of 13 patients with newly diagnosed BP, before starting treatment. The aim of the study was to evaluate this method as a diagnostic tool in BP. Our results indicate that blister-fluid examination by ELISA can be a useful tool to diagnose bullous pemphigoid, especially in elderly patients who refuse biopsy or have poor venous access.