Delayed decline of gamma-globin expression in infant age associated with the presence of Ggamma-158 (C-->T) polymorphism.

Persistent production of fetal hemoglobin (HbF) in adult has ameliorative effects on hemoglobinopathies and great efforts are currently made to achieve an exhaustive understanding of the molecular mechanisms of the switching in globin gene expression. One of the factors reported to be associated with the expression of fetal globin genes is the Xmn I Ggamma-158 polymorphism, although it is still unclear if it is involved in this mechanism either by itself or in strong linkage disequilibrium with other loci. Here, we report a novel effect of the Xmn I Ggamma-158 site that was found associated with a significant delayed decline of HbF production in infant age. The prolonged decay trend was enhanced when the Ggamma-158 C-->T substitution was co-inherited with a beta-thalassemic trait. Our observations reinforce the hypothesis that this region plays an important role in the expression of the gamma-globin genes and give new insights on the intriguing and still poorly understood mechanisms of globin gene expression switching.

Lipid profile in beta-thalassemia intermedia patients: correlation with erythroid bone marrow activity.

Lipid abnormalities, including low levels of all fractions of serum lipids, have been repeatedly reported in all phenotypes of beta-thalassemia. Unexpectedly, in more recent studies, the concentration of total cholesterol (TC) and high- and/or low-density lipoprotein cholesterol (HDL-C and LDL-C) has been found in beta-thalassemia intermedia (TI) patients even lower than in thalassemia major, without a clear explanation of pathophysiology of these findings. This lack of information prompted us to evaluate the plasma lipids and lipoproteins pattern in the TI patients followed in our department; the data were compared with those found in hereditary spherocytosis patients. Furthermore, in both groups of patients, the erythroid bone marrow activity was evaluated, utilizing the level of soluble transferrin receptors (sTfR) in the plasma. Both groups of patients showed similar lipid abnormalities (low-TC, HDL-C and LDL-C) and the same increase of sTfR, with significantly lower hemoglobin levels in TI patients. Data analysis of our study shows that the lipid profile in TI patients is not influenced by age, sex, liver injury, hemoglobin or ferritin levels; the higher erythroid bone marrow activity with the enhanced cholesterol consumption could be the dominant mechanism implicated in the lipid abnormalities of TI patients.

Unchanged iron and copper and increased zinc in the blood of obese children after two hypocaloric diets.

Serum iron (sFe), and ferritin (sFert), transferrin saturation index (TSI), plasma zinc and copper (pZn, pCu), and erythrocyte zinc content (eZn) were measured in 55 obese children and adolescents (28 males and 27 females) before and after a 13-wk treatment with a hypocaloric balanced diet (HCBD, 22 subjects) or a 10-wk treatment with a protein sparing modified fast diet (PSMF, 33 subjects). The energy intake provided by the HCBD and PSMF diet was calculated to be 60 and 25%, respectively, of the recommended dietary allowances (RDAs) for age and sex. Neither diet was supplemented with trace elements or calcium. Using a visual memory system, all subjects had a 24-h dietary intake recall before starting the weight-loss program. Iron, zinc, and copper intakes from the 24-h recall were compared with those from prescribed diets. Both diets produced a significant (p < 0.001) weight reduction with a significant reduction in the arm muscle area of the PSMF group. After treatment, no significant change was observed in sFe, sFert, and TSI of either group, whereas eZn increased significantly in the HCBD and the PSMF groups (p = 0.001 and p < 0.006, respectively), with an improvement of the erythrocyte index (E.I.). A significant increase in pZn was also observed in the PSMF group (p = 0.007).

Growth retardation in non-steroid treated juvenile rheumatoid arthritis.

Growth in height was studied in 58 patients with juvenile rheumatoid arthritis (JRA) followed for 4.9 +/- (SD) 2.8 years, who had never received steroids. Height measurements were converted to Height Z Scores. Height Z scores at first and at last visit were respectively 0.7 +/- 1 and 0.7 +/- 0.9 (NS) in pauciarticular, 0 +/- 1.6 and -0.55 +/- 1.6 (p = 0.045) in systemic, 0.29 +/- 0.8 and -0.4 +/- 1 (p = 0.0001) in polyarticular JRA patients. In systemic and polyarticular patients a significant negative relation was found between the duration of disease and the delta Height Z score (p = 0.0008) as well as between the sum of the periods of active disease and the delta Height Z score (p = 0.0001). The patients with functional class = 1 lost 0.01 +/- 0.19 Height Z score per year while those with functional class > or = 2 lost 0.16 +/- 0.13 Height Z score per year (p = 0.005). The loss of Height Z score in systemic and polyarticular subjects observed during pubertal age (-0.71 +/- 0.67 Height Z score) was significantly (p = 0.02) greater than in those observed before puberty (-0.1 +/- 0.72). The longer duration of disease, the higher degree of functional joint involvement, and the age of puberty appear to be risk factors for height growth impairment in systemic and polyarticular JRA.

Prevalence of alcohol problems in general practice: an experience from southern Italy.

The Michigan Alcoholism Screening Test (MAST) and the response to a question about heavy alcohol consumption were used to assess the prevalence of alcohol problems in consecutive patients (77 males and 46 females) consulting a general practitioner in an urban area in the South of Italy (Castellammare di Stabia). Alcohol problems, which were defined by a cut-off score of 5 on the MAST and/or by heavy alcohol consumption (corresponding to at least 60 g of ethanol daily for males and 36 g of ethanol daily for females for at least 2 years), were identified in 54 patients [43.9%; 95% confidence interval (CI) 35.0-53.1%], 45 males (58.4%; 95% CI 46.6-69.6%) and nine females (19.6%; 95% CI 9.4-33.9%). The prevalence of MAST positive patients was 32.5% (95% CI 24.4-41.6%) in the total patient sample, 45.5% (95% CI 34.1-57.2%) among males and 10.9% (95% CI 3.6-23.6%) among females. The question about heavy alcohol consumption had a predictive negative value of 97.2% (95% CI 90.2-99.7%) and a predictive positive value of 73.1% (95% CI 59.0-84.4%) in relation to MAST positive patients. It is suggested that general practitioners should incorporate this question about heavy alcohol consumption as a screening question in order to detect alcohol problems and give advice regarding reduction of alcohol consumption.

Nutritional status in active juvenile chronic arthritis not treated with steroids.

Nutritional status and nutrient intake were assessed in 17 children with active juvenile chronic arthritis (JCA) who never received steroids and in 17 controls matched for age and sex. Five patients had systemic, seven polyarticular and five oligoarticular JCA. Values significantly below those of the controls were found in systemic patients for height (p<0.05), upper arm circumference (p<0.05) and arm muscle area (p<0.01), and in polyarticular subjects for arm muscle area (p<0.01). All patients had unremarkable anthropometric fat measurements. All anthropometric measurements were normal in oligoarticular patients. Twelve JCA patients had reduced serum iron (Fe), 6 reduced serum zinc (SZn), 14 reduced intra-erythrocytic zinc (EZn) and 2 reduced serum copper (SCu). SZn was inversely correlated with erythrocyte sedimentation rate (ESR) (p=0.023). EZn was inversely related to lymphocyte count (p=0.022). SCu was related to ESR (p=0.037) and to lymphocyte count (p=0.016). No significant difference in nutrient intake was found between patients and controls. Active JCA was associated with reduced muscular mass, Fe, SZn, EZn. These alterations did not depend on reduced nutrient intake.

Bone mineral content in nephrotic children on long-term, alternate-day prednisone therapy.

Bone mineral content (BMC) was measured by single-photon absorptiometry in 24 children with steroid-dependent, minimal-lesion nephrotic syndrome after 1 to 6.3 years of alternate-day prednisone therapy and in a sex- and age-matched control group. Bone mineral content was -0.002 +/- 1.2 standard deviation scores in patients and 0.3 +/- 1.4 in controls (t = 1.17; P = 0.25). No significant relation was found between BMC in patients and the amount of prednisone taken or the duration of therapy. Alternate-day prednisone therapy at doses usually needed to keep children with steroid-dependent nephrotic syndrome under control does not significantly affect BMC.

Reduced bone mineral content and normal serum osteocalcin in non-steroid-treated patients with juvenile rheumatoid arthritis.

OBJECTIVES: To distinguish the effects of juvenile rheumatoid arthritis (JRA) on bone mineralisation from those possibly caused by steroid therapy. METHODS: Bone mineral status was evaluated in 20 children (five boys and 15 girls) with active JRA who never received steroids. Seven had oligoarticular, nine had polyarticular, and four had systemic JRA. Bone mineral content (BMC) was assessed by single beam photon absorptiometry and expressed as a Z score relative to normal values in healthy children. Serum calcium, phosphate, and alkaline phosphatase were measured by colorimetric methods. Whole parathyroid hormone was assayed by Immuno Radiometric Assay. Serum osteocalcin was measured by specific radioimmunoassay. Nutrient intake was assessed by a 24 hours dietary recall. BMC and nutrient intake were also assessed in an age and sex matched control group. RESULTS: BMC was -1.5 (SEM 0.8) Z scores in patients and 0.4 (0.3) in the control group (p = 0.02). BMC averaged -4.9 (2) Z scores in the systemic JRA group, -1 (0.6) in the polyarticular group and 0.3 (0.7) in oligoarticular JRA patients. Serum calcium, phosphate and osteocalcin values were normal in all patients. No significant difference was found between JRA patients and controls in calcium, phosphate, energy, and protein intake. CONCLUSION: JRA subjects have significantly reduced BMC even in the absence of any steroid therapy. Bone demineralisation appears to depend more on disease activity and on reduced motility than on reduced nutrient intake.

Progression of chronic renal failure.

The deterioration rate of creatinine clearance (CCr) was studied in 40 children with chronic renal failure (CRF) on conservative treatment followed up for at least 1 year (range 1-12). The deterioration rate of CCr was significantly (p less than 0.01) higher in glomerulopathies (G) than in hypoplasias (H) and in vascular nephropathies (VN) and significantly (p less than 0.01) higher in hereditary nephropathies (HN) than in VN. The differences in the deterioration rate of CCr between H and HN and between H and VN were not explainable on the basis of the different age at diagnosis or of the different prevalence of hypertension. These data indicate that the primary renal disease is important in determining the progression of CRF.