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.

Evaluation of children with lympadenopathy.

AIM: To examine children who present with enlargement of lymph nodes in terms of demographic, clinical, serological and radiological aspects. MATERIAL AND METHODS: Ninety-eight patients who presented with a complaint of enlargement of lymph nodes were examined in terms of demographic, clinical, serological and radiological aspects by screening file data retrospectively. The character of lymph nodes (reactive, malign) was evaluated according to the distribution, number, sizes and blood supply determined in ultrasonographic measurements. Fisher's Exact test and Mann-Whitney U Test were used in comparison of the groups. Kappa value was used in assessment of compatibility between the two groups. RESULTS: Cervical lymphadenomegaly was found most frequently in accordance with the complaint of swelling in the neck. Erythrocyte sedimentation rate, ultrasonography, Epstein-Barr virus (EBV) and cytomegalovirus (CMV) IgM were not found to be statistically significatly different between the normal and abnormal physical examination groups (erythrocyte sedimentation rate; p=0.623, USG; p=0.753, EBV and CMV; p=1.00). Cytomegalovirus and EBV IgM were not found to be statistically significatly different between the normal and abnormal ultrasonography groups (CMV; p=0.35, EBV; p=0.36). There was no compatibility between physical examination and ultrasonography (=0.32). CONCLUSION: Lymphadenopathy is a common problem in the childhood and necessitates a careful physical examination and follow-up. Laboratory and imaging methods should be used when necessary. Although lymphadenopathy is mostly related with infections, care should be taken in terms of malignancy and malignancy should be eliminated. The important point is systemic evaluation and follow-up of the patient. It is important to note physical examination findings and clinical follow-up findings, because frequent ultrasonographic investigations may confuse physicians and families with high values of lymph node measurements despite normal physical examination. Therefore, using our fingertips with a good physical examination is still our most sensitive diagnostic tool instead of ultrasonography.

Primary vertebral lymphoma presenting with fracture.

We report a 15 year old girl admitted with back pain and multifocal osteolytic lesions without systemic symptoms at T7, L5, and S1 spinal vertebras. The child was diagnosed as having primary multifocal osseous lymphoma, in which multiple bones are involved in the absence of lymph node or visceral disease for at least 6 months following initial presentation.

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.

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.

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.

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.

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.

Proanthocyanidin prevents methotrexate-induced intestinal damage and oxidative stress.

Mucositis is an important dose-limiting side effect of methotrexate for which there is no definitive prophylaxis or treatment. This study was designed to investigate whether proanthocyanidin had a protective effect on methotrexate-induced small intestine damage. Twenty-eight albino rats were randomized into four groups. To the first group, methotrexate was applied as a single dose (20mg/kg) intraperitoneally. To the second group, proanthocyanidin (100mg/kg) was given orally every day by gavage in addition to methotrexate application until the rats were killed. To the third group, only proanthocyanidin was administered. The fourth group was the control. All animals were sacrificed 4 days after the intraperitoneal injection of methotrexate for histopathological examination and the assay for tissue malondialdehyde, superoxide dismutase and glutathione peroxidase levels. Methotrexate caused jejunal injury and increased malondialdehyde levels. Administration of proanthocyanidin decreased the jejunal damage and malondialdehyde level, which were caused by methotrexate treatment and increased superoxide dismutase and glutathione peroxidase levels. These results suggest that proanthocyanidin may protect the small intestine of rats from methotrexate-induced damage. The effects of proanthocyanidin could result from its antioxidant properties.

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.

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.

Ozone ameliorates methotrexate-induced intestinal injury in rats.

Methotrexate (Mtx) is an effective chemotherapeutic agent used in various cancer treatments. Gastrointestinal toxicity is the drug's major limiting factor, arising mainly from oxidative damage. It has been proposed that ozone (O(3)) is an activator of antioxidant enzymes. Thus, this study was designed to investigate the efficacy of ozone therapy in the prevention of Mtx-induced intestinal injury in rats. Twenty rats were allocated into three groups: sham, Mtx alone (untreated) and Mtx + O(3) (treated with ozone). Ozone was administered at a dose of 0.72 mg/kg daily via an intraperitoneal route for 15 d. On d 16, Mtx was applied via an intraperitoneal injection at a dose of 6 mg/kg for 5 d. All rats were sacrificed at d 21. Efficacy of the treatment was assessed by measuring the histopathologic injury score (HIS), and biochemically by determining tissue superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) in ileum, liver and kidney homogenates. Although two rats (25%) died in the untreated group, all rats in the sham and treatment groups survived the study. The HIS, antioxidant enzyme and MDA levels of the ileal tissue were significantly lower in the ozone treated group than the untreated group (p < 0.05). Although the antioxidant enzyme and MDA levels of liver and kidney were significantly lower in the ozone treated group (p < 0.05), there was no significant change in histopathology (p > 0.05). Thus, ozone preconditioning shows a preventative effect in the ileum by decreasing tissue damage and increasing antioxidant enzyme activity in an experimental model of Mtx-induced intestinal injury.

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.

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.

Post varicella hepatic actinomycosis in a 5-year-old girl mimicking acute abdomen.

Actinomycosis is an indolent, slowly progressive infection caused by gram-positive, anaerobic or microaerophilic bacteria. Hepatic involvement is rare and generally secondary to abdominal or thoracic actinomycosis. Hepatic actinomycosis in children may mimic a wide variety of diseases and thus make the diagnosis much more challenging. Here, we report a 5-year-old girl with apparently primary hepatic actinomycosis mimicking acute abdomen 2 weeks after varicella. The diagnosis was made by ultrasonic guided fine needle aspiration biopsy of a hypoechoic lesion of 3.5 cm diameter in the liver showing sulfur granules surrounded by neutrophils. Hepatic actinomycosis should be taken into account when evaluating acute abdomen symptoms in children.

Development of in situ melanoma after allogeneic bone marrow transplantation in Griscelli syndrome type II.

GS is an uncommon autosomal recessive disorder characterized by pigmentary dilution of the skin and hair and in most patients by abnormal regulation of the immune system. Childhood melanoma is rare in the pediatric population. The best prognosis is achieved with early diagnosis and definitive surgical excision of melanoma. We report a case of a patient with GS type II and melanoma who was successfully treated by allogeneic bone marrow transplantation and surgical excision of the melanoma.

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.