Dimitris A. Papanastasiou

First urinary tract infection in neonates, infants and young children: a comparative study

In an attempt to evaluate first urinary tract infection (UTI) in neonates and infants, we estimated retrospectively in 296 patients (62 neonates and 234 infants) clinical and laboratory findings, occurrence of vesicoureteral reflux (VUR), urinary tract abnormalities and pyelonephritis. First UTI occurred more often in male than female neonates, whereas male and female infants/young children were affected at an equal rate. The pathogens isolated in urine cultures of neonates and infants did not statistically significantly differ (P>0.05); Escherichia coli predominated. Gram-negative bacteria other than E. coli affected boys more often than girls (P=0.0022). Fever was the most frequent symptom. Neonates had lower-grade fever of shorter duration than infants (P<0.05). The incidence of reflux and urinary tract abnormalities did not differ between neonates and infants, male and female neonates and infants (P>0.05). Pyelonephritis affected neonates and infants at an equal rate; it was more prevalent among female patients (P=0.038) and patients with VUR or urinary tract abnormalities other than VUR (P<0.0001). Neonates with reflux were more often affected by Gram-negative bacteria other than E. coli than were neonates without reflux (P=0.0008).

Community-associated Staphylococcus aureus infections and nasal carriage among children: molecular microbial data and clinical characteristics

An increasing number of infections caused by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) carrying the Panton-Valentine leukocidin (PVL) genes was recently identified in Greece. In the present study, 170 patients with S. aureus infections and 123 uninfected children (<15 years old) who had been tested for nasal carriage were evaluated during a 2-year period. The MecA, PVL and superantigen family genes, and MRSA clones, were investigated by molecular methods. Sites of infection and laboratory findings for patients were recorded. The results were compared and statistically analysed. Among 123 uninfected children 73 (59%) carried S. aureus, including four MRSA strains. Of these, three MRSA and three methicillin-sensitive S. aureus (MSSA) strains were PVL-positive (p <0.0001). Ninety-six patients (96/170) exhibited skin and soft-tissue infections (SSTIs), and 74 exhibited invasive infections. The incidence of staphylococcal infections increased during July to September each year. In total, 110 S. aureus isolates were PVL-positive (81 from SSTIs and 29 from invasive infections, p <0.0001). Ninety-nine out of 106 MRSA (93%) isolates from 170 patients carried the PVL genes (p <0.0001); 97 belonged to the clonal complex CC80. Leukocyte and polymorphonuclear cell counts were higher among children with MRSA infections (p <0.005). MSSA predominated among patients with invasive infections (43/74), and carried mainly genes of the superantigen family. Children <5 years of age showed a higher risk of MRSA infection. The present study demonstrates that infections due to PVL-positive CA-MRSA spread easily among children, and SSTIs can lead to invasive infections. Nasal colonization may be an additional factor contributing to the emergence of CA-MRSA.

Concentration of iron and distribution of iron and transferrin after experimental iron overload in rat tissues in vivo: study of the liver, the spleen, the central nervous system and other organs.

The purpose of this study was to estimate the iron concentration in the liver, spleen and brain of control rats and rats overloaded with iron and to determine the distribution of iron and of transferrin (TF). Iron was administered to Wistar rats by food supplemented with 3% carbonyl iron for 3 months, or intraperitoneally, or intraveneously as iron polymaltose for 4 months (total administered dose: 300 or 350 mg/rat, respectively). Iron concentration was estimated by atomic absorption spectrophotometry and iron- and TF-distribution histochemically and immunohistochemically, respectively. In control rats the organ with the highest iron content was the spleen, followed by the liver and brain. After iron loading the increase of iron in the liver was greater than that of the spleen; iron concentration in the brain did not change significantly. Distribution of iron in the liver was in Kupffer cells throughout the lobule and in hepatocytes at its periphery. No difference in the number of positive cells or staining intensity for TF was observed between control rats and iron overloaded animals in the liver or central nervous system (CNS); the spleen was negative for TF. Distribution of TF in the liver showed a centrilobular localisation in hepatocytes. TF reaction in the brain occurred in oligodendrocytes, vessel walls, choroid plexus epithelial cells and some neurons. In conclusion, experimental iron overload in rats leads to iron uptake mainly by reticuloendothelial (RE) cells and hepatocytes, indicating that hepatocytes are of particular importance for iron metabolism. Iron uptake by the brain was not significant, probably because the brain is protected against iron overload. Iron overload did not influence location and quantity of TF in the liver and CNS, whereas the visualisation of iron and TF did not coincide. This indicates that TF may have other functions beyond iron transport.

Ocular Abnormalities in Patients with β Thalassemia

We examined 29 patients with homozygous β thalassemia. The mean age of the patients was 15.6 ± 8.9 years. Twelve patients (mean age, 02.0 ± 10.4 years) had one or more ocular abnormalities. Five patients had degeneration of the retinal pigment epithelium, one had lens opacities, two had lens opacities and degeneration of the retinal pigment epithelium, one had vascular abnormalities and degeneration of the retinal pigment epithelium, one had angioid streaks, lens opacities, and degeneration of the retinal pigment epithelium, and two had angioid streaks and degeneration of the retinal pigment epithelium. These abnormalities were observed in patients with both forms of β thalassemia, major and intermedia. The frequency of the ocular abnormalities increased with age. The youngest patient with an ocular abnormality was 6 ½ years old. There was no correlation between the abnormalities observed and the serum ferritin level, the mean hematocrit value, and the dose of deferoxamine given to the patients.

Response to interferon alfa-2b therapy in multitransfused children with beta-thalassemia and chronic hepatitis C

Abstract Hepatitis C virus is responsible for the majority of cases of post-transfusion non-A non-B hepatitis in patients with thalassemia major. Interferon alfa is an effective treatment for patients with chronic hepatitis C. Response to therapy is related to the duration of treatment, the viral load in serum, and the hepatitis C virus genotype. The purpose of this study was to estimate the response of multitransfused children with β-thalassemia and chronic hepatitis C to interferon alfa-2b therapy. Thirteen patients with β-thalassemia and chronic hepatitis C, (mean age±SD, 14.1±1.7 years) participated in the study. Liver biopsy, estimation of HCV RNA, and virus genotyping were performed before onset of treatment. All patients were positive for HCV RNA in a low concentration; two patients carried the 1a genotype, four had genotype 3, and seven had genotype 4. Patients were treated with 3×106 U of subcutaneous interferon alfa-2b three times weekly. Eleven of 13 patients received therapy for 18 months; the remaining two underwent therapy for 6 months. Six of 13 patients responded completely to therapy, four responded partially, and three did not respond at all. The grade of inflammation and stage of fibrosis was lower in complete responders. Complete responders had lower ferritin values compared with the values for partial and nonresponders before starting therapy. The results suggest that interferon therapy should be recommended for children with β-thalassemia major complicated by a low viral concentration of hepatitis C.

Incidence of scoliosis in β−thalassemia and follow-up evaluation

STUDY DESIGN: One hundred fifteen of 120 patients with beta-thalassemia followed in the thalassemia unit were studied for the presence of scoliosis. Forty-nine of these patients were reevaluated 1 year later. OBJECTIVES: To determine the frequency and the course of scoliosis in beta-thalassemia and to compare the findings with those of patients with idiopathic scoliosis. SUMMARY AND BACKGROUND DATA: There is only one report indicating increased frequency of scoliosis in a limited number of patients with thalassemia. In this study, the authors assessed the frequency of scoliosis in a large sample of patients and followed the evolution of this spinal deformity. METHODS: Patients with beta-thalassemia aged 3-35 years were examined clinically and radiologically for scoliosis. Forty-nine of them were reexamined 1 year later for determination of the evolution of scoliosis. RESULTS: Lateral curves of at least 5 degrees Cobb were found in 77 patients (67%), with a male-to-female ratio of 0.9. Scoliosis of at least 10 degrees was found in 21.7% of the male and 20% of the female patients with thalassemia. The ratio was 1.18 for curves of at least 10 degrees and 0.77 for curves of a smaller magnitude. The most common curve pattern was the left lumbar (35.1%), followed by the double-curve pattern (16.9%). Forty-nine randomly selected patients (42.6%) of the 115 included in the study were reexamined 1 year later. Seven male and 7 female patients (total, 28.6%) showed a progression of at least 5 degrees. Six patients (12.2%) experienced spontaneous improvement of less than 6 degrees. The pattern and the evolution of scoliosis observed in patients with beta-thalassemia differ from those found in Greek children with idiopathic scoliosis. CONCLUSIONS: The findings of this study show that the incidence, evolution, and etiology of scoliosis in beta-thalassemia differ from those of idiopathic scoliosis, indicating that the spinal deformities in patients with beta-thalassemia represents a distinct type of scoliosis. Longer follow-up is needed to investigate the natural history of this type of scoliosis.

Prevalence of scoliosis in beta-thalassemia.

The objective of this study was to determine the prevalence and possible pathogenesis of scoliosis in beta-thalassemia in our country, and to compare its characteristics to those of patients with idiopathic scoliosis from the same geographic area. Twenty-four [13 male and 11 female thalassemic patients aged 16 +/- 7 years (range 7-32 years)] of 115 examined patients with beta-thalassemia showed scoliosis of 14 degrees +/- 11 (range 10-65 degrees) radiologically. The prevalence of scoliosis in the thalassemic population was 21% in this series, whereas the overall prevalence of scoliosis in the general Greek population was 6% (Smyrnis PN, Valavanis J, Alexopoulos A, Siderakis G, Giannestras NJ: School screening for scoliosis in Athens, J Bone Joint Surg 61B:215-217, 1979). The scoliosis prevalence in the general population was significantly higher in the females (5%) than in the males (1%), whereas no difference in prevalence was found between the two sexes in the thalassemic population. The most common curve pattern in thalassemia was the left lumbar (38%) followed by the right lumbar (21%), whereas in patients with idiopathic scoliosis the left thoracolumbar most commonly appeared (25%) followed by the left lumbar (14%). No patient with thalassemia showed radiographic signs of congenital spinal deformities and spinal fractures, whereas all patients showed a significant retardation of their skeletal maturation. The age of the thalassemic patients with scoliosis was significantly (p = 0.0003) higher than in patients without scoliosis. The hematocrit of the thalassemic patients with scoliosis was significantly (p = 0.0012) lower than in those without scoliosis, whereas the rate of transfusions was not correlated with the magnitude of the scoliosis. The level of ferritin was significantly (p = 0.025) higher in the thalassemic patients with scoliosis than in those without scoliosis. The duration of Desferal treatment was significantly (p = 0.0357) longer in thalassemic patients with scoliosis when compared with those without scoliosis. Thus, the prevalence, curve pattern, and etiology of scoliosis in beta-thalassemia differ from those of idiopathic scoliosis, indicating that the spinal deformities in thalassemia represent a distinct type of scoliosis.

Correlative analysis of the sagittal profile of the spine in patients with β-thalassemia and in healthy persons

This prospective study compares several roentgenographic parameters of the thoracic and lumbar spine in patients with beta-thalassemia and in healthy persons who served as controls. Eighty-four patients with beta-thalassemia and 84 age- and gender-matched healthy persons were examined clinically and radiologically (thoracic kyphosis, lumbar lordosis, and vertebral and sacral inclination). Although there was a significant difference in the vertebral inclination from T6 to L1, L4, and L5 between patients and controls, thoracic kyphosis and lumbar lordosis did not differ in the two groups. The apical vertebra of the thoracic kyphosis in patients and controls was T7 and T6, respectively, whereas L4 was the apical vertebra of the lumbar lordosis in both groups. There were no age- or gender-related differences in the magnitude of sacral inclination, thoracic kyphosis, or lumbar lordosis in the patients with beta-thalassemia compared with controls. Lumbar lordosis was significantly correlated with sacral inclination in both patients with beta-thalassemia and controls. Beta-thalassemia does not affect sagittal profile of the thoracic and lumbar spine but it is associated by structural changes on the frontal plane of the spine that are expressed as a high prevalence of scoliosis.

Natural history of untreated scoliosis in β-thalassemia

Study Design. A prospective study was performed. Objectives. To investigate the natural history of untreated scoliosis in &bgr;-thalassemia patients in a 10-year period. Summary of Background Data. Several previous studies have demonstrated the bone deformities, particularly the high incidence of scoliosis, that is associated with &bgr;-thalassemia. However, little is known about the evolution of scoliosis curvatures, and almost nothing is known about the natural history of this type of scoliosis and its associated lateral spinal curvatures. Methods. From a group of 115 patients with &bgr;-thalassemia who were evaluated for scoliosis 10 years ago, 43 patients (37%) were re-evaluated 10 years later to study the evolution of the untreated scoliosis and lateral spinal curvatures. Scoliosis, thoracic kyphosis, thoracolumbar kyphosis, and lumbar lordosis were measured both in the initial and last observation and were compared with each other. All changes in scoliosis curve location, direction, and rate of resolving, as well as the changes in the magnitude of the lateral spine curves, were recorded. Results. Scoliosis curves of more than 5° were present in 34 (79%) of the 43 patients who were followed. Scoliosis progressed but was not statistically significant in 12% of the patients with thalassemia in a 10-year span. Ten years ago, 12 patients (28%) showed scoliosis of 10° to 14°, whereas in the last evaluation, 15 patients (35%) had scoliosis of 10° to 19°. The S-shaped scoliosis curve pattern was the most common (29%). In 10 years, the scoliosis curve pattern remained unchanged in 38% of the patients, and it changed in 38%, whereas 24% of the minor curves (5–9°) showed spontaneous “self-resolving” character. In the last evaluation, there were seven patients (16%) with new cases of scoliosis de novo. There was no sex-related predominance in prevalence of scoliosis in this series. There was a significant skeletal mature retardation in the patients with &bgr;-thalassemia. There was a significant increase of thoracic and thoracolumbar kyphosis and a decrease of lumbar lordosis. The changes in the sagittal profile were not correlated to scoliosis in this group of patients. Conclusions. Scoliosis in &bgr;-thalassemia appeared with increased prevalence but with small curves of 5° to 19° that did not need active orthopedic treatment. However, a few cases progressed to curves less than 20°, and only one patient (2.9%) showed a severe curve that showed much progression. The behavior of scoliosis in &bgr;-thalassemia differs significantly from that in idiopathic scoliosis. The skeletal disorders that are caused by this hematologic dysfunction seem to be responsible for the spinal deformities and their evolution.

Lack of Transmission of Hepatitis C in Household Contacts of Children with Homozygous β-Thalassaemia

Forty-eight household contacts of 25 children with homozygous beta-thalassaemia and chronic hepatitis C (index cases) were evaluated for antibodies against hepatitis C virus (HCV) and increased transaminase values in the blood. The mean age +/- SD of the household contacts was 36.4 +/- 17.0 years (range 5-67) and 20 of them were males. All thalassaemic patients (age 14.3 +/- 3.0 years, range 8-19) were positive for anti-HCV antibodies by repeated determinations. HCV-RNA was detected in the blood of 22 of 23 patients tested by polymerase chain reaction. Liver biopsies were performed in 18 patients and showed chronic active hepatitis in 14 and chronic persistent hepatitis in 4. The mean duration of contact between the index cases and the household contacts while the index cases were anti-HCV positive was 45.3 +/- 10.2 months (range 17-57). None of the household contacts was found to be positive for anti-HCV antibodies nor did they have elevated transaminases in the two examinations performed within an interval of about 2 years. Among the HCV-negative household contacts are included 14 who mentioned needlestick injuries with needles used by the index cases.