Serum hepcidin levels and iron metabolism in obese children with and without fatty liver: case-control study.

UNLABELLED: Hepcidin is a regulator of iron balance that is increased in obesity. It reduces the absorption of iron, reduces the transfer of iron from macrophages to the plasma and/or prevents mobilisation of stored iron. Obese patients with non-alcoholic fatty liver disease (NAFLD) demonstrate adipokine and cytokine release promoting inflammatory response. We aimed to analyse the hepcidin levels and iron metabolism in obese children with and without NAFLD and non-obese healthy controls. The study population consisted of 110 children aged 7-18 years in three groups: 50 obese patients without NAFLD, 30 obese patients with NAFLD, and 30 non-obese healthy controls. Serum hepcidin, ferritin, and iron levels, iron-binding capacity, lipid profile, and liver function tests were measured, and hepatic ultrasonography was performed in all participants. Obese patients' white blood cell counts, total cholesterol, triglyceride levels, and homeostatic model assessment of insulin resistance (HOMA-IR) were significantly higher than those of the control group. Iron-binding capacity was significantly higher in obese patients without NAFLD compared with obese patients with NAFLD (p = 0.002). Hepcidin levels were not significantly different between obese patients and the control group. However, hepcidin levels in obese patients with NAFLD were significantly higher than those in obese patients without NAFLD (p < 0.001). CONCLUSIONS: Hepcidin levels were significantly higher in obese children with NAFLD than those without NAFLD. Obese children with NAFLD should receive attention regarding iron metabolism disorders. Serum hepcidin could be a marker of iron metabolism status and NAFLD in these groups of patients.

Mutations in SLC29A3, encoding an equilibrative nucleoside transporter ENT3, cause a familial histiocytosis syndrome (Faisalabad histiocytosis) and familial Rosai-Dorfman disease.

The histiocytoses are a heterogeneous group of disorders characterised by an excessive number of histiocytes. In most cases the pathophysiology is unclear and treatment is nonspecific. Faisalabad histiocytosis (FHC) (MIM 602782) has been classed as an autosomal recessively inherited form of histiocytosis with similarities to Rosai-Dorfman disease (RDD) (also known as sinus histiocytosis with massive lymphadenopathy (SHML)). To elucidate the molecular basis of FHC, we performed autozygosity mapping studies in a large consanguineous family and identified a novel locus at chromosome 10q22.1. Mutation analysis of candidate genes within the target interval identified biallelic germline mutations in SLC29A3 in the FHC kindred and in two families reported to have familial RDD. Analysis of SLC29A3 expression during mouse embryogenesis revealed widespread expression by e14.5 with prominent expression in the central nervous system, eye, inner ear, and epithelial tissues including the gastrointestinal tract. SLC29A3 encodes an intracellular equilibrative nucleoside transporter (hENT3) with affinity for adenosine. Recently germline mutations in SLC29A3 were also described in two rare autosomal recessive disorders with overlapping phenotypes: (a) H syndrome (MIM 612391) that is characterised by cutaneous hyperpigmentation and hypertrichosis, hepatomegaly, heart anomalies, hearing loss, and hypogonadism; and (b) PHID (pigmented hypertrichosis with insulin-dependent diabetes mellitus) syndrome. Our findings suggest that a variety of clinical diagnoses (H and PHID syndromes, FHC, and familial RDD) can be included in a new diagnostic category of SLC29A3 spectrum disorder.

Pulmonary tuberculosis mimicking metastasis in a patient with osteosarcoma.

Pulmonary metastasis even at diagnosis or during treatment is an important problem in osteosarcoma treatment and treatment modality varies in patients with metastasis. Metastasectomy and aggressive induction chemotherapy are the 2 most well-known treatment options. However, reactivation of pulmonary tuberculosis can be a problem in developing countries, where the prevalence of tuberculosis is high. Here, we described a patient with osteosarcoma with pulmonary tuberculosis reactivation mimicking metastasis.

Melatonin ameliorates doxorubicin-induced skin necrosis in rats.

Doxorubicin (DXR), a highly effective chemotherapeutic agent, causes serious injury when extravasated. The injury can sometimes result in skin necrosis and ulceration, requiring surgery. The detrimental effect of DXR on the antioxidant system via free oxygen radicals is one of the mechanisms proposed in its etiology. Thus, we used melatonin, a potent antioxidant, and compared the effects with dimethylsulfoxide (DMSO), which is used in the treatment of patients with DXR-induced extravasation.Twenty-seven Wistar-albino rats were used. After intradermal injection of DXR, DMSO was injected into the extravasated area and melatonin was given intraperitoneally. On day 14 of the experiment, skin ulcers were clearly formed and samples were taken with a punch biopsy. Ulcer sizes were measured. Tissue samples were analyzed for superoxide dismutase, glutathione peroxidase, and malondialdehyde enzymes, and histopathologically evaluated.Melatonin clearly decreased MDA levels, ulcer size, and histopathologic ulcer scores in DXR extravasated tissue. DMSO also decreased MDA levels, ulcer size and histopathologic ulcer score. However, melatonin was remarkably more effective than DMSO in terms of antioxidant enzyme activity, oxidative stress, and histopathologic ulcer scores in rats. Necrosis was evident in the DXR-treated group and some slides showed necrosis involving the fascia. Histopathologic ulcer scores of the necrotic tissue decreased in the DMSO and melatonin groups. The ulcer score in the melatonin group was significantly lower than in the control group. Although the ulcer score in the DMSO group was lower than control, there was no statistically significant difference. The ulcer size in the DMSO group was significantly lower than the control group. The ulcer size in the melatonin group was significantly lower than both the DMSO and control groups.We believe that melatonin, either alone or in combination with DMSO, may be used for treating DXR extravasation. In addition, free oxygen radicals play a crucial role in the etiology of the injury, which should be considered in further studies.

Primary gastric Burkitt lymphoma: a rare cause of intraabdominal mass in childhood.

Primary gastric lymphoma in the pediatric population is rare and the role of Helicobacter Pylori (H. Pylori) in its pathogenesis is unclear. In this report, we describe a case of non-Hodgkin's lymphoma (Burkitt's type) coexisting with H. pylori and discuss the potential relationship between H. Pylori and gastric Burkitt lymphoma.

Alpha-fetoprotein producing tumor cells in children with Wilms' tumor.

Alpha fetoprotein (AFP) is generally used as a marker in diagnosis and follow-up of germ cell tumors and hepatoblastomas. However, serum AFP levels were elevated in our three patients with Wilms tumor. The elevated levels could only be decreased completely by surgery and not by chemotherapy. Histopathologically, the tumors consisted of blastemal, stromal, and epithelial cells. Chemotherapy was only effective on stromal and epithelial components of the tumors. In AFP staining, the source of AFP production was identified as blastemal tumor cells. Because the increased AFP levels were decreased after surgery, AFP levels may be used in the follow-up of the patients with Wilms tumor. Herein, we report three patients with Wilms tumor whose serum AFP levels were elevated and who had diffuse WT-1 and focal AFP expression in all tumors, immunohistochemically.

Hematopoietic stem cell transplantation in Langerhans cell histiocytosis: case report and review of the literature.

The prognosis in children with LCH who do not respond to the conventional therapies is very poor. SCT may be a new approach. However, there are limited data about the results of the transplantations. Herein we report a patient with refractory multisystem LCH who underwent allogeneic bone marrow transplantation and is disease and treatment free 54 months after transplantation. Further studies are required to establish the role of SCT in refractory LCH.

Cardioprotective roles of aged garlic extract, grape seed proanthocyanidin, and hazelnut on doxorubicin-induced cardiotoxicity.

Doxorubicin (DXR) is a chemotherapeutic agent used effectively in the treatment of several childhood malignancies. During treatment, cardiotoxicity caused by cell damage due to the free oxygen radicals that are generated is a major limiting factor. This study was undertaken to determine whether DXR-induced cardiotoxicity could be prevented by natural foods with antioxidant properties such as aged garlic extract (AGEX), grape seed proanthocyanidin (PA), and hazelnut. Wistar albino male rats were assigned randomly to 9 groups each consisting of 15 rats. AGEX, PA, and hazelnut groups received these antioxidants in addition to their standard rat diet. They were also treated with cumulative intraperitoneal (i.p.) injections according to 2 different regimens: either a high-dose of 15 mg/kg DXR (3.75 mg/kg per week for 4 weeks) or a low-dose of 7.5 mg/kg DXR (1.875 mg/kg per week for 4 weeks). The control group received i.p. 0.9% saline. AGEX, PA, or hazelnut supplements were given orally to the groups for a 6-week period starting 1 week before the DXR treatment and ending 1 week after the treatment. One week after the last DXR injection, heart tissue samples were analyzed to determine malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and xanthine oxidase (XO) levels, and serum samples were taken for creatine kinase (CK). There were no significant changes in MDA levels among the control, DXR-treated groups, or supplemented groups that received additional natural antioxidant foods. SOD enzyme levels were decreased in rats treated with DXR. PA prevented the decrease at low doses of DXR. DXR treatment decreased CAT enzyme levels, but additional PA and hazelnut consumption increased these levels at low cumulative doses. XO enzyme levels were decreased in AGEX and hazelnut groups, but PA prevented the decrease. CK levels were elevated after DXR administration, indicating myocardial injury, but PA significantly reversed this. Although there were no differences histopathologically between AGEX, PA, and hazelnut groups, the protective effects of AGEX and PA were evident in electron microscopy. In conclusion, the positive effects of natural antioxidant foods on the prevention of DXR-induced cardiac injury could not be clearly shown on the basis of antioxidant enzymes. However, the electron microscopic changes clearly demonstrated the protective effects of AGEX and PA. The supplementation of these antioxidant foods over longer periods may show more definitive results. Human studies with different doses are needed to evaluate the effects of these foods on the human heart.

Hepatoblastoma metastatic to the right atrium responding to chemotherapy alone.

An 18-month-old boy presented with abdominal pain and distension. On physical examination there was a 10 x 7-cm mass in the right upper abdominal quadrant. His alpha-fetoprotein level was 175,000 IU/mL. Abdominal magnetic resonance findings revealed hepatomegaly with multiple tumor masses involving nearly all the segments of the liver (PRETEXT IV). The tumor extended through the inferior vena cava and filled 2/3 of the right atrium. Echocardiography revealed normal cardiac function. Histopathologic findings after liver biopsy were consistent with hepatoblastoma. After 6 courses of chemotherapy including cisplatin and doxorubicin (PLADO, SIOPEL protocol), the cardiac tumor regressed completely. The patient's primary tumor was then fully resected; no cardiac surgery was performed. After surgery the AFP level was 4 IU/mL and echocardiography revealed normal cardiac function with no residual tumor. The patient has been in remission for 31 months postdiagnosis.

Transfusion-related acute lung injury in a child with neuroblastoma during a late engraftment period of autologous stem cell transplantation.

TRALI is a rare and serious complication of blood product transfusion characterized by acute respiratory distress, non-cardiogenic pulmonary edema, hypoxia, fever, and hypotension developing during or up to six h following transfusion. The disease can be life-threatening and should be considered whenever complications occur after a transfusion in stem cell transplant recipients. Caution should be exercised as the symptoms of TRALI are similar to diseases such as pulmonary hemorrhage, pulmonary edema, and engraftment syndrome. The neutrophil engraftment generally occurs after 14 days following allogeneic stem cell transplants. The diagnosis of TRALI becomes very difficult with late engraftments. Herein, we report TRALI in a pediatric recipient whose neutrophil engraftment occurred on day 67.

Nosocomial outbreak of Sphingomonas paucimobilis bacteremia in a hemato/oncology unit.

Nosocomial Sphingomonas paucimobilis infections can arise from contaminated water and the contaminated hands of hospital staff. Within a 1-month period, we isolated six S. paucimobilis strains, including four from blood cultures of four patients and two from hospital environment specimens including tap water and a bathtub in a hemato/oncology unit. We described here these strains' molecular epidemiological analyses by pulsed-field gel electrophoresis (PFGE) and antibiotic susceptibilities by E-test. Although clinical and environmental isolates yielded three different antibiotic resistances and PFGE patterns, all four clinical strains had an identical pattern by both methods. Thus, the isolated clinical strain clone could be traced neither to health care workers nor to environmental samples. It was concluded that S. paucimobilis strains can cause outbreaks in hemato/oncology units. We did not demonstrate genetic relatedness between clinical and environmental isolates by PFGE, but did find PFGE a useful identification technique for epidemiological investigation.

Stroke associated with pseudoephedrine in a child with rhabdomyosarcoma.

Pseudoephedrine is a nasal vasoconstrictor and is contained in many cough and cold medications. It is generally harmless when used in recommended doses. Hypertensive crisis, psychosis, hemorrhagic stroke, and intracranial hemorrhage have been reported as severe complications. We report a 4-year-old girl with nasopharyngeal rhabdomyosarcoma who developed stroke while on pseudoephedrine therapy for 3 days and had no hematological abnormalities.

Bone mass toxicity associated with inhalation exposure to toluene.

The inhalation of a wide range of organic solvents has become popular among young adults. Toluene is one of the most commonly used solvents in industry; it is easily available and convenient to use. Many toxicologic effects on biological systems secondary to deliberate inhalation of toluene have been reported, but investigations on adverse effects associated with bone morbidity is limited. The purpose of this study is to determine bone mineralization and investigate the adverse effects of toluene on bone. The bone mineral density and content of the femoral neck of mice exposed to toluene at 300 ppm for 8 wk were measured by dual X-ray absorptiometry and found significantly reduced compared to the control group. Chronic exposure to toluene was found to affect bone metabolism, and toluene-induced changes could contribute to bone resorption and inhibition of bone formation. Toluene seems to be the responsible component for the demineralizating effects of commonly abused substances, and medical doctors must promote their education about the health hazards in those who abuse solvents especially in areas where inhalant abuse is endemic.

Cardiac troponin I: is it a marker to detect cardiotoxicity in children treated with doxorubicin?

Doxorubicin has been used in the the treatment of malignant tumors in children. Its use is limited by cardiotoxic effects beyond a cumulative dose of 450 mg/m2. To detect cardiotoxicity at an early stage and identify patients at risk for development of cardiotoxicity are matters of concern. Recently, cardiac troponin I (cTnI) has been reported to be useful for detecting minor myocardial damage. In the present study, we investigated whether cumulative doxorubicin-related myocardial cell damage can potentially increase cTnI levels above the expected values in 22 patients treated with cumulative doxorubicin doses of 120 to 450 mg/m2. Impaired cardiac functions were found in three patients by echocardiography, but serum CTnI levels were within the ranges expected in healthy individuals both in patients with cumulative doxorubicin doses > or = 400 mg/m2 and in patients with disturbed cardiac functions. We found no relationship between serum cTnI, cumulative dose of doxorubicin, and echocardiographical findings.

An interesting case of childhood brucellosis with unusual features.

Brucellosis is a zoonotic infection, which is still a major public health concern worldwide. Common clinical findings are usually nonspecific involving fever, arthralgia, myalgia, weakness and malaise. Since none of the symptoms of brucellosis is pathognomonic, it may have a similar course with various multisystemic diseases. In terms of focal involvement, sacroiliitis is the most common musculoskeletal manifestation in adult patients, while it is quite rare in pediatric patients. Blood culture is the gold standard in the diagnosis of brucellosis. In the absence of culture facilities, the diagnosis traditionally relies on serologic testing with a variety of agglutination tests such as the Rose Bengal test and the serum agglutination test. However, these agglutination tests are accompanied by frequent false negative results such as seen in prozone phenomenon, which may lead to diagnostic delays. In this article we present a rarely encountered pediatric brucellosis patient who had sacroiliitis-spondylitis, which are rarely reported in children, and exhibited prozone phenomenon in agglutination tests.

Cardiac troponin-I, brain natriuretic peptide and endothelin-1 levels in a rat model of doxorubicin-induced cardiac injury.

BACKGROUND: Cardiotoxicity, during or after therapy, is the most serious side effect of doxorubicin (DXR). The risk of developing cardiac impairment increases concomitantly with an increase in the cumulative dose of DXR. AIM: The aim was to evaluate the levels of cardiac troponin-I (cTnI), brain natriuretic peptide (BNP) and endothelin-1 (ET-1) in DXR induced cardiac injury. MATERIALS AND METHODS: Thirty-nine Wistar albino rats were divided into three groups; a control group and two-study groups that received low-dose DXR (LDD) and high-dose DXR (HDD) in a weekly schedule for reaching a cumulative dose. RESULTS: Serum cTnI level was significantly increased in both LDD and HDD-treated groups. Although serum BNP was not significantly increased either LDD or HDD-treated groups, ET-1 levels was significantly increased in only HDD-treated groups. Histopathologic injury was more evident in HDD-treated group. CONCLUSIONS: Serum cTnI was increased even in LDD and parallel to it low cardiac injury induced by DXR. In the low-dose group, BNP and ET-1 levels were not elevated significant as cTnI despite cardiac injury. Thus, cTnI may be a predictive marker in of DXR-induced cardiotoxicity.

Blood lead levels in glue sniffers.

The aim of this study was to investigate blood levels of lead (Pb) among adolescents with glue sniffing in Turkey. Blood Pb levels were measured in 30 adolescent glue sniffers by atomic absorption spectrophotometry and compared with those of the 30 healthy adolescents. The Pb contents of various glue preparations marketed in Turkey and used by the abusers were also measured. Blood Pb levels were significantly higher in the study group when compared to the control group. Pb was detected at considerably high levels in the contents of all the various glue preparations most commonly used by the cases in the study group. The increased blood Pb levels in glue sniffers may be related to the high lead contents of glues marketed in Turkey. The blood Pb levels and signs of Pb toxicity should be investigated in examination of glue sniffers.

Bone mineral density in children with nocturnal enuresis.

In enuretic children there is a significantly higher incidence of fine and gross motor clumsiness, delayed developmental milestones, slower and poor linear growth, and these patients are shorter than normal children. Skeletal maturation of enuretic children has been determined with bone age in only two studies before, but to our knowledge bone mineral content of enuretic children has not previously been determined by bone mineral density measurement. Bone mineral density was measured by the dual-energy x-ray absorptiometry method in children with nocturnal enuresis and compared with that of a control group to detect whether there were any delay in bone development and any decrease in bone mass. Thirty enuretic children were compared with a control group of 40 healthy children with respect to body height and weight measurements, daily calcium intake, serum calcium, phosphorus and ALP levels, chronological and bone ages, and bone mineral density measurements. Of the parameters compared, bone age was significantly retarded, and bone mineral density was significantly reduced in children with enuresis (8.3 +/- 1.9 vs 9.7 +/- 2.3 years; p = 0.01, and 0.5476 +/- 0.07 vs 0.6077 +/- 0.05 g/cm2; p = 0.001, respectively). Chronological ages demonstrated a significant correlation with the bone ages in both the study and control groups (r = 0.852, p < 0.001, and r = 0.844, p < 0.001, respectively). However, the mean chronological age was significantly greater than the mean bone age in the study group (p < 0.001), whereas the mean chronological age was not significantly different from the mean bone age in the control group (p = 0.514). To clarify the exact mechanism responsible for these manifestations of skeletal maturation retardation, the relationship between the maturational delay of the central nervous system connections or the effect of any perinatal insult and the retardation in skeletal maturation remains to be determined.