Neuroimaging Features of Biotinidase Deficiency.

Biotinidase deficiency is an autosomal recessive condition caused by pathogenic variants in the BTD gene. Resultant deficiency of free biotin leads to impaired activity of the enzyme carboxylase and related neurologic, dermatologic, and ocular symptoms. Many of these are reversible on treatment, but early recognition and commencement of biotin supplementation are critical. This practice is especially important in countries where routine neonatal screening for biotinidase deficiency is not performed. In this report comprising 14 patients from multiple centers, we demonstrate the MR imaging patterns of this disorder at various age groups. Knowledge of these patterns in the appropriate clinical context will help guide early diagnosis of this treatable metabolic disorder.

Neuroradiological, neurophysiological and molecular findings in infantile Krabbe disease: two case reports.

Krabbe disease is an autosomal recessive neurodegenerative disorder due to a defect of the lysosomal enzyme ß-galactocerebrosidase (ß-GALC). Depending on the age of onset, the disease is classified into infantile and later-onset forms. We report neuroradiological, neurophysiological and molecular findings in two Greek patients with the infantile form of Krabbe disease. The index patients presented at the age of 3.5 and 6 months, respectively, due to developmental delay. Magnetic resonance imaging (MRI) of the first patient's brain demonstrated signs of leukodystrophy, while nerve conduction velocities (NCVs) were significantly decreased. The second patient's MRI at the age of 4 months was initially normal, but at 18 months demonstrated leukodystrophic alterations as well, whereas NCVs were also significantly delayed. In both patients, a severe decrease in ß-GALC, activity supported the diagnosis of Krabbe disease, while the final diagnosis was confirmed by molecular genetic testing. Two homozygous mutations of the GALC gene, the c.411_413delTAA [p.K139del] mutation in the first patient, and the c.749T>C [p.I250T] mutation in the second patient, were identified. At their last follow-up visit at the age of 4 and 6 years, respectively, both patients were bedridden and quadri-plegic, suffering from frequent respiratory tract infections and fed through a gastrostomy. Both mutations found in homozygosity in these two unrelated patients of Greek ancestry, could pinpoint a common origin. Genotyping of patients with Krabbe disease is important, in order to contribute to the creation of a European mutation database and to further study possible genotype-phenotype correlations of the disease.

Brain and spinal MR imaging findings in mucopolysaccharidoses: a review.

MPS represents a group of rare hereditary disorders characterized by multisystem involvement due to intralysosomal GAG accumulation. Among various tissues, both the central and peripheral nervous system are affected in almost all types of the disease. Thus, brain and spinal MR imaging are valuable tools for the assessment of neurologic involvement, and there is evidence that they might be reliable markers demonstrating disease severity and efficacy of treatment options currently used in patients with MPS. We aimed to review the most prominent MR imaging features of patients with MPS, paying attention to the physiopathologic mechanisms responsible for these alterations. Along with the description of neuroimaging findings, existing data in relation to their correlation with the severity of neurologic involvement is discussed, while another topic of great importance is the effect of various therapeutic regimens in the progression of brain and spinal MR imaging alterations. Finally, recent data concerning MR spectroscopy studies in MPS are also critically discussed.

Fairy tales: a compass for children's healthy development--a qualitative study in a Greek island.

BACKGROUND: Fairy tales have always been an integrated part of children's everyday life. In our days, they still represent important ways of helping the children share their desires and express their agonies and inner conflicts. The present descriptive qualitative study aims to describe parents' opinions and children's preferences regarding storytelling. METHODS: Four hundred and seventy parents took part in the study and were interviewed following a semi-structured guide with open-ended trigger questions. Data were processed via content analysis methods. RESULTS: Three main themes were constructed. The vast majority of interviewees acknowledged their strong belief in the power of fairy tales and stated that their children listen to stories at least once a week. Most of them use storytelling as an instructive tool, in order to soothe their children's anxieties or set examples for them. Concerning children's preferences, the majority of them choose classic fairy tales over modern ones with Little Red Riding Hood taking precedence over other famous stories. All participants acknowledged the fact that their children are amused and positively affected by storytelling, while young readers share their enthusiasm for fairy tales in many ways, mostly by talking about their favourite character. Finally, in relation to the villains, children seem to be satisfied or relieved when they are punished and only a small number of participants stated that the cruel punishment of bad characters creates feelings of fear to their kids. CONCLUSIONS: The findings of this study emphasize the crucial role that storytelling plays in children's life and normal development.

A "sweet" hydrothorax in a child on peritoneal dialysis.

Peritoneal dialysis (PD) is an established, effective long term renal replacement treatment modality for children with end stage renal disease (ESRD). A rarely reported complication of PD in children is the development of hydrothorax1. We report the case of an 8-year-old boy that developed a right-sided pleural effusion during automated PD (APD), in order to raise awareness amongst paediatricians; we also review the diversity of clinical presentation and the available diagnostic tools, discuss theories regarding aetiology and highlight the available treatment options.

Treatment of colorectal cancer with and without bevacizumab: a phase III study.

OBJECTIVE: The objective of this phase III trial was to compare chemotherapy combined with bevacizumab versus chemotherapy alone in the treatment of patients with advanced colorectal cancer. METHODS: From September 2004 till September 2008, 222 treatment-naive patients were enrolled and divided into 2 arms: 114 arm A patients were treated with leucovorin, 5-fluorouracil plus irinotecan in combination with bevacizumab, and 108 arm B patients were treated as above without bevacizumab. All patients were stage IV with histologically confirmed adenocarcinoma. RESULTS: The median overall survival of arm A patients was 22.0 months (95% CI: 18.1-25.9) and 25.0 months (CI: 18.1-31.9) for arm B patients. There was no statistically significant difference between the 2 arms (p = 0.1391). No statistically significant difference between the 2 arms regarding the response rate was observed: partial response, 42 patients (36.8%) and 38 patients (35.2%) for arms A and B, respectively. Hematologic toxicity did not differ in the comparison of the 2 arms. Nonhematologic toxicity in arm A involved hypertension in 23 (20.2%) of the patients and proteinuria in 7 (6.1%); 3 patients experienced hemorrhage and 1 patient intestinal perforation. None of these side effects was observed in arm B patients. CONCLUSION: No statistically significant difference in median overall survival in patients with advanced colorectal cancer treated with bevacizumab plus a combination therapy (arm A) and those treated with the combination only, without bevacizumab (arm B), was observed.

Multiple myeloma and bone disease: pathogenesis and current therapeutic approaches.

Multiple myeloma is a haematologic malignancy caused by clonal expansion of malignant plasma cells and associated with bone disease and hypercalcaemia. Myeloma cells are in close proximity to sites of active bone resorption and the interactions between those cells, osteoblasts and osteoclasts, are crucial not only for the bone distraction but for the proliferation of bone marrow cells as well. Recent studies have revealed that numerous regulating factors of osteoblast and osteoclast activity interfere with the pathogenesis of multiple myeloma's bone disease and that the understanding of the pathophysiological pathways involved is the first step towards discovering novel potential therapeutic approaches.

Angiosarcoma of the heart: case report and review of the literature.

BACKGROUND: Primary angiosarcoma of the heart is an extremely rare malignant disease. PATIENTS AND METHODS: A 32-year-old female with primary angiosarcoma of the heart at an advanced stage with lung and bone metastases is presented. The tumor showed extensive expression of c-erb-B2 and a moderate expression of c-kit. Chemotherapy (cisplatin, epirubicin and ifosfamide) was administered. Herceptin as well as glivec were added to the above combination. RESULTS: There was a good partial response and the lung deposits almost disappeared. The duration of response was 6 months. CONCLUSION: This case of angiosarcoma of the heart is presented because of the extreme rarity of this disease, and its responsiveness to chemotherapy in combination with imatinib and herceptin.

Primitive neurectodermal tumors: a case of extraosseous Ewing's sarcoma of the small intestine and review of the literature.

This is a review of extraosseous Ewing's sarcoma (ES) which includes a new, extremely rare case. The literature was examined with respect to determining the locations of extraosseous ESs, the incidence per site and in total and the criteria which confirm the similarity between extraosseous and osseous ES. ES sites were detected in several organs and tissues, mainly in the trunk, extremities and the retroperitoneal region. Studies confirmed that osseous and extraosseous ES are identical chromosomally and histologically. ES of the small intestine, described here, has not been previously documented in the literature. Along with the other different documented sites, a new location of primary extraosseous ES is also reported here.

Combination chemotherapy with carboplatin, docetaxel, and gemcitabine in advanced non-small-cell lung cancer: a phase II study.

PURPOSE: To evaluate the efficacy and toxicity of the combination of carboplatin, docetaxel, and gemcitabine in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-five chemotherapy-naive patients with NSCLC were treated on an out-patient basis with carboplatin area under the curve 5 intravenous (IV) and gemcitabine 800 mg/m(2) IV on day 1 and docetaxel 75 mg/m(2) IV and gemcitabine 800 mg/m(2) IV on day 8. Granulocyte colony-stimulating factor (150 ug/m(2) subcutaneously) was given prophylactically from day 3 to day 6 and day 10 to day 16. Chemotherapy was repeated every 4 weeks. Patients were evaluated for response every two cycles of treatment. RESULTS: The median age of the patients was 58 years (range, 24 to 75 years). The performance status was 0 for 16 patients, 1 for 17 patients, and 2 for 12 patients. Nine patients (20%) had stage IIIB disease, and 36 (80%) had stage IV; histology was mainly squamous cell carcinoma (51.2% of patients) that was poorly differentiated (37.8%). All 45 patients were assessable for toxicity, and 41 were assessable for response. On an intent-to-treat analysis, the objective response rate was 46. 5% (21 out of 45 patients; 95% confidence interval [CI], 31.7% to 62. 5%). Of the 45 patients, four (8.8%) achieved a complete response (95% CI, 2.5% to 21.2%); 17 (37.7%) achieved a partial response (95% CI, 23.8% to 53.5%); seven (15.5%) had stable disease; and 14 (31. 1%) had progressive disease. The median survival time was 13.5 months, and the actuarial 1-year survival rate was 51.11%. The median duration of response was 7.6 months, and the time to tumor progression was 8.1 months. Grade 3/4 anemia and thrombocytopenia occurred in 17.7% and 28.8% of patients, respectively. Twenty-one patients (46.6%) developed grade 3/4 neutropenia, and six patients (13.3%) were complicated with fever. Alopecia was universal. Grade 3 diarrhea occurred in four patients (8.8%); grade 3/4 neurotoxicity occurred in 10 patients (22.2%); and grade 2/3 allergic reaction occurred in three patients (16.6%). There were no treatment-related deaths. Six patients (13.3%) required a dose reduction, two of which required two reductions. CONCLUSIONS: The combination of carboplatin, docetaxel, and gemcitabine is an effective regimen for the treatment of chemotherapy-naive patients with advanced NSCLC, causing only moderate toxicity.