Comparison of the Ovary and Kidney as Sites for Islet Transplantation in Diabetic Rats.

BACKGROUND: Currently, the most commonly used site for clinical islet transplantation is the liver although it is far from being an ideal site. Low oxygen tension and the induction of an inflammatory response impair islet implantation and lead to significant early loss of islet. The present study aimed to investigate and compare the efficacy of islet transplantation to the ovary and kidney subcapsule in diabetic rats. METHODS: The study was performed with 3 groups of rats (control, ovary, and kidney subcapsule) including 6 Sprague female rats each. Diabetes model was created with the use of streptozotocin, and blood glucose levels of the rats were measured after 72 hours. Thirty days after the transplantation, blood samples were obtained from the rats, and then pancreas, kidney, and ovary specimens were fixed in 10% formaldehyde and the experiment completed. After staining with hematoxylin and eosin, the tissue samples were morphologically evaluated by a specialist histopathologist. RESULTS: Changes in mean blood glucose and C-peptide levels were statistically significant in the ovary and kidney subcapsule groups. Histologic examination revealed that granulosus insulin-bearing cells were detected in the islet grafts of both ovary and kidney subcapsule groups. The renal subcapsule group had inflammation signs on histologic examination. The islet cells of both ovary and renal subcapsule groups had no vacuolization. CONCLUSIONS: We showed that the ovary might be a new site for islet transplantation. Further research should be done on whether the initial results of this study can be reproduced in larger numbers of animal models and eventually in humans.

Effect of stem cell application on Asherman syndrome, an experimental rat model.

PURPOSE: We evaluate the effect of stem cells to induce endometrial proliferation and angiogenesis on Asherman Syndrome (AS). METHODS: The experimental study was performed in stemcell research laboratory. Forty Wistar-Albino rats were divided according to groups. In group1 (n = 10) to establish the model; trichloroacetic acid was injected to right uterine horn. Two weeks later, intrauterine synechia was confirmed. In group2 (n = 10), 2 weeks later, 2 × 106 mesenchymal stem cells (MSC) were injected into right uterine horn followed by three intraperitoneal injections of MSCs. In group3 (n = 10), daily oral estrogen was initiated on the second week. In group4 (n = 10), MSC injections and oral estrogen was given together. The amount of fibrosis, vascularisation, inflammation and immunohistochemical staining with vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA) and Ki-67 were evaluated in the uterine tissues. RESULTS: In all treatment groups; fibrosis decreased but vascularisation and immunhistohemical stainings increased in the experimental side. The amount of fibrosis, vascularisation, Ki-67 and PCNA scores were similar between group2 and 3. In group4, comparing to group2, less fibrosis but more Ki-67, PCNA and VEGF staining was observed. CONCLUSION: Stem cells, when added to estrogen, are a highly effective alternative to induce regeneration of endometrium in Asherman Syndrome therapy.

The utility of NT-proBNP and various echocardiographic methods in the determination of doxorubicin induced subclinical late cardiotoxicity.

BACKGROUND AND AIM: Our aims were to investigate the utility of plasma N terminal-pro B-type natriuretic peptide (NT-proBNP) level and find the most beneficial echocardiographic parameters to detect subclinical cardiotoxicity in childhood- cancer survivors treated with doxorubicin. METHODS: The study included 23 patients with a mean age of 17.1 years, who had received doxorubicin therapy with a mean cumulative dose of 241.1 mg/m2 with a median time period of 10.5 years since the last dose of doxorubicin. The control group consisted of 19 healthy volunteers matched for age, sex, and weight. RESULTS: The serum NT-proBNP levels of the patient group were higher than the control group. The measurements of myocardial performance index (MPI), tissue Doppler mitral septal annulus systolic (S's) and early diastolic (E's) velocities, ratio of early mitral flow velocity (E) to E's (E/E's), left ventricular diastolic volume (LVDV), tricuspid early diastolic velocity (TE) and percentage of left ventricular posterior wall thickness (%LVPWt) were found to be significantly different from the control group. MPI values were significantly correlated with NT-proBNP levels and cumulative doxorubicin doses. CONCLUSIONS: Elevated MPI values, associated with high NT-pro BNP levels and high cumulative doxorubicin doses, could be a useful indicator of subclinical cardiotoxicity. NT-proBNP could be an effective marker in the long-term follow up of subclinical cardiotoxicity.

Effect of osteoblast cell culture on the bone implant contact.

PURPOSE: The aim of this study is to acquire an ideal bone implant contact under the cover of osteogenic effect of osteoblasts derived from Mesenchymal Stem Cells (MSCs). MATERIALS AND METHODS: Thirty dental implants were used for this study. Implants were placed in sheep mandibles and defects were created 4 mm coronally in the dental implants. These defects were filled with Platelet Rich Plasma (PRP) in one group and with PRP + Osteoblast Cell Culture (OCC) in another group. No procedure was conducted on the control group defects (empty defect group). Eight weeks later, osseointegration was investigated with Bone Implant Contact (BIC) measurements histomorphologically. Data were checked statistically. RESULTS: The variation of BIC rates between Empty Defect Group and PRP groups was significant (p <0.05). The BIC rate of the PRP group was higher than that of the Empty Defect Group. The variation of BIC rates between Empty Defect Group and PRP + OCC groups was significant (p <0.05). The BIC rate of the PRP + OCC group was higher than that of the Empty Defect Group. The variation of BIC rates between PRP and PRP + MSC groups was significant (p<0.05). The BIC rate of the PRP + OCC group was higher than that of the PRP group. At the end of the 8-week healing period, it was observed that the percentage of BIC was highest in the PRP + OCC group. CONCLUSIONS: Implant-bone connection was better in the OCC-PRP group compared with the PRP group and the empty defect group. The use of OCC-PRP combination was effective on healing. The BIC value was increased significantly by OCC.

Serum osteopontin and CD44 levels in lymphoreticular malignancies in children.

OBJECTIVE: Osteopontin (OPN) is an adhesive glycoprotein that interacts with a variety of cell surface receptors, including several integrins and CD44. OPN is expressed and secreted by numerous human malignancies. CD44 play an important role in tumor growth and metastasis. We aimed to evaluate serum levels of osteopontin and CD44 in patients with lymphorethicular malignancies in childhood. METHODS: We studied serum levels of CD44 and OPN levels of 54 patients (26, 18 and 10 patients with non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HL) and acute lymphoblastic leukemia (ALL), respectively) at the diagnosis. RESULTS: The mean levels of OPN were significantly higher in patients (5.42±8.24 ng/ml) than in controls (3.89 ±1.96 ng/ml). The mean levels of CD44 levels were also significantly higher in patients (3.82±2.31 ng/ml) than in controls (1.96±0.62 ng/ml), and significantly higher in the advanced stages than in early stages. The mean levels of the CD44 in NHL, HL and ALL were 3.49±2.00, 3.56±1.74, and 5.15±3.50 respectively. OPN and CD44 levels were found to be increased in parallel (p=0.003). A more advanced disease and/or poor prognostic factors were seen in 9 patients who had both serum CD44 and OPN levels higher than 2SD of the control. CONCLUSION: Elevated levels of both CD44 and OPN at the diagnosis may predict an unfavorable outcome in childhood leukemias and lymphomas (Tab. 2, Fig. 3, Ref. 44).

Early diagnosis of anthracycline toxicity in asymptomatic long-term survivors: dobutamine stress echocardiography and tissue Doppler velocities in normal and abnormal myocardial wall motion.

AIMS: Asymptomatic long-term cancer survivors treated with anthracycline were investigated for late anthracycline cardiotoxicity using dobutamine stress echocardiography (DSE) and tissue Doppler (TD) velocities. METHODS AND RESULTS: The study comprised 20 asymptomatic patient and 18 healthy children as the control group. Twenty patients were divided into two groups according to the myocardial wall motion during DSE: Group 1 (normal myocardial wall motion; six girls and five boys) and Group 2 (abnormal myocardial wall motion: nine boys). Intravenous dobutamine infusion was started at a dose of 5 µg/kg/min (D5) and gradually increased to 10 (D10), 15 (D15) and 20 µg/kg/min (D20). Echocardiographic assessment was performed at rest and after each dose of dobutamine infusion. Abnormal myocardial wall motion was observed at rest in 3 patients and during DSE in six patients. There were no significant differences between the patients and control groups at rest except the end systolic wall stress and mitral deceleration time measured by conventional methods; however, both patients group showed significant differences of systolic and diastolic functions at D20. In patients groups, systolic and diastolic functions of interventricular septum (IVS) and systolic function of left ventricle (LV) and right ventricle (RV) TD velocities showed significant changes compared with control group at rest. Significant differences of diastolic functions of IVS and RV were noted during dobutamine infusion in abnormal myocardial wall motion compared with other groups. CONCLUSION: LV, RV and IVS TD velocities systolic function at rest and during DSE can provide valuable information for early detection of subclinical cardiac toxicity. TD velocities of diastolic functions during DSE are a valuable parameter for assessment of subclinical cardiac toxicity in patient with abnormal wall motion.

Tissue and flow myocardial performance index measurements taken during dobutamine stress echocardiography for early diagnosis of late anthracycline cardiotoxicity.

The purpose of this study was to define the role of tissue and flow myocardial performance index (MPI) measured during dobutamine stress and tissue Doppler echocardiography in the early diagnosis of late cardiotoxicity among patients with childhood cancer treated with anthracycline. The study included 20 patients (14 male and 6 female; mean age 18.4 +/- 3.2 years) as the study group and 18 healthy volunteers (14 female and 4 male, mean age: 19.2 +/- 4.0) as the control group. The mean cumulative dose of anthracycline treatment was 282.1 +/- 125.9 mg/m2, and the mean time period after the last dose of anthracycline was 10.2 +/- 4.0 years. Echocardiography was performed during rest and at infusions of 5, 10, 15, and 20 micro/kg/min dobutamine. Although only isovolumetric relaxation and contraction times of the patient group were prolonged at rest, dobutamine infusion showed significant differences in % left ventricle (LV) posterior wall thickening, LV end-systolic wall stress, LV diastolic and systolic diameter, mitral acceleration, and deceleration time in the patient group compared with the control group. Tissue and flow MPI of the LV, tissue MPI of the right ventricle (RV), and interventricular septum of the patient group were higher than the control group throughout the test. LV tissue MPI increased much more than LV flow MPI when stress was increased. In conclusion, LV tissue MPI value during stress is more valuable than LV flow MPI in the early diagnosis of late cardiotoxicity. RV function can be assessed by tissue Doppler MPI.

Is oxidative damage in operation in patients with hereditary spastic paraparesis?

Oxidative stress resulting from increased free radical production and/or defects in antioxidant defences may be the cause of various neurodegenerative disorders. In this study, the roles of oxygen free radicals, nitric oxide, superoxide dismutase, vitamin E and vitamin C were investigated in pure and complicated hereditary spastic paraparesis (HSP) patients. The results showed that plasma SOD, vitamin E and nitric oxide levels were significantly low in HSP patients. These findings indicate the influence of oxidative damage in the degenerative process of HSP.

Complementary/alternative medicine use in a pediatric oncology unit in Turkey.

BACKGROUND: Important in the cancer therapy is the increasingly use of complementary/alternative medicine (CAM). The current study aims to establish the extent of use, the types of therapies employed, factors influencing, the reasons for choosing and the cost of CAM used in pediatric cancer patients in our clinic in Ankara, Turkey. PROCEDURE: A detailed questionnaire regarding demographic data and information about the use of CAM was completed by 95 patients who have attended the clinic between 1999 and 2000. RESULTS: Forty-nine patients (51.6%) had used one or more than one type of CAM. The most frequent (71.4%) was herbal medicine and biologic intake (stinging nettle, plant essence, honey of Anzer). The second one was religious therapy (40.8%). No correlation could be found between the use of CAM and parents education status, the level of income, number of siblings, the prognosis of the disease, the rate of satisfaction with the level of information given by the doctor at the time of diagnosis or the belief in the information given by the doctor about the prognosis (P > 0.05). All patients used CAM in addition to conventional therapy. CONCLUSIONS: More than half of the patients used CAM, with stinging nettle being the most common agent. Our patients place a high level of trust in their physicians and the conventional therapies offered by them; however, they also believe that the complementary therapies are harmless and, therefore, worth trying.

Late effects of treatment on growth in childhood non-Hodgkin's lymphoma.

Growth impairment is one of the most important late sequelae in childhood malignancies. In the last few years, the contribution of cytotoxic agents to growth retardation has been a subject of investigation. The aim of this study was to evaluate the growth impairment in children treated for non-Hodgkin's lymphoma (NHL). The study group comprised 41 children (eight girls, 33 boys) treated for NHL with three different chemotherapy protocols. All patients were in remission at the last visit. The control group consisted of 41 healthy age- and sex-matched children. All patients' standing heights and body weights were measured regularly from the time of diagnosis. Growth parameters were measured both at the time of diagnosis and at the end of treatment (median treatment time: 6 months). Height and weight velocities were calculated at 6 month intervals after the diagnosis until the last visit. The mean height SDS of the patients was -0.66 +/- 1.42 at the diagnosis and 0.29 +/- 1.21 at the last visit. Height SDS of the patients showed a significant improvement at the end of the 2nd year after the diagnosis (p = 0.005) and at the last visit (p = 0.022) (median follow-up time: 48 months after diagnosis). The height velocity SDS increase at the end of the 2nd year was particularly remarkable in short-term protocols such as BFM-90 B-NHL. The sitting height, the sitting height/height ratio and serum insulin-like growth factor-I (IGF-I) levels were found to be lower in the patients than those of control group at the last visit. One can conclude that chemotherapy might cause a reduction in growth velocity during treatment. The cumulative dosages of anti-neoplastic agents and serum IGF-I levels could have been implied in the pathogenesis of growth retardation.

Childhood craniofacial Burkitt's lymphoma presenting as maxillary swelling: report of a case and review of literature.

Burkitt's lymphoma (BL) is an undifferentiated malignant lymphoma comprising of uniformly primitive lymphoreticular cells. The tumor was seen originally in patients in Africa. African type BL usually occurs in the jaws of young children. In American cases, abdominal involvement predominates. Strong evidence implicats Epstein-Barr virus in the development of BL. BL is found most commonly in childhood, with a peak incidence in African cases at 5 to 8 years old and in American cases at 10 to 12 years old. The disease shows a preference for males in a 2:1 to 4:1 ratio. BL is the most rapidly growing neoplasm requiring immediate diagnosis and treatment; however, it is extremely sensitive to chemotherapy. In this report, a case of BL that was initially misdiagnosed as an acute dental abscess is presented and the role of the dentist in the diagnosis and treatment of these patients is emphasized.

Electrocardiographic findings after 5-HT3 receptor antagonists and chemotherapy in children with cancer.

BACKGROUND: The antiemetic efficacy of serotonin-type 3 (5-HT3) receptor antagonists has been found to be superior to older antiemetic drugs in cancer patients. Following the administration of these agents, changes in ECG parameters and increased or decreased heart rates have been demonstrated, but there is no sufficient data in children with cancer who are treated with cytotoxic agents. The objective of this study is to evaluate the ECG changes after administration of 5-HT3 receptor antagonists and chemotherapeutic agents in children with cancer. PROCEDURE: Thirty-eight patients with an age range between 2 and 19 years receiving chemotherapy for solid tumors were included in the study. The patients received 5-HT3 receptor antagonists 30 min before antineoplastic agents in 83 chemotherapy days. Antiemetic therapy consisted of ondansetron in 43 and granisetron in 40 chemotherapy days. Twelve-leads ECGs were obtained four times at the first day of each chemotherapy: just before 30, 90 min, and 24 hr after 5-HT3 receptor antagonists were given. Rate, rhythm, PR interval, QRS duration, ST segment, the shortest (QTca) and the longest (QTcb) QTc intervals with QTc dispersion (QTcd) were all evaluated. RESULTS: We found a significant shortening of the PR interval and QRS complex durations in the granisetron group at 90th min and at 24th hr, respectively. Also, granisetron infusion caused a significant prolongation of the QTca interval at 90 min. CONCLUSION: Although we observed minor ECG changes after 5-HT3 receptor antagonists and chemotherapy, neither dangerous rhythm disturbances nor serious ECG changes were seen.

Prognostic factors and treatment outcome in childhood Hodgkin disease.

BACKGROUND: The goals of this study included: (1) Identification of factors prognostic for event-free survival (EFS) and overall survival (OS), and (2) Definition of risk groups for risk adapted therapy in children with Hodgkin disease (HD). PROCEDURE: From 1991 to 2003, 69 children with newly diagnosed, untreated biopsy-proven stage I-IV HD were treated with chemotherapy (CT) and low-dose involved field radiotherapy (LD-IFRT). The relationship of pretreatment factors to EFS and OS was analyzed by univariate and multivariate analysis. RESULTS: The 5-year EFS and OS for all patients were 90.77% and 96.22%, respectively with a median follow-up of 73 months (3-137 months). Male to female ratio was 3:1 and 21 children (32.3%) were less than 7 years of age. Mixed cellularity was the predominant histologic subtype (38.5%). Factors associated with inferior EFS by univariate analysis were extranodal disease, hemoglobin level <11 g/dl, number of involved lymph node regions and stage. By multivariate analysis only stage IV disease was significant. CONCLUSION: Our study confirms that excellent results are achievable with combined modality therapy in childhood HD. In order to use risk-adapted therapy in children with HD, clinical prognostic factors should be validated with large, multicentered prospective clinical studies.

Type II pleuropulmonary blastoma responsive to multimodal therapy.

Pleuropulmonary blastoma is a rare and aggressive primary intrathoracic neoplasm of children. T'he prognosis is extremely poor with frequent metastasis to the brain and bone. A 4-year-old boy successfully treated with multimodal therapy despite unfavorable prognostic factors is presented. The authors support the use of aggressive treatment of pleuropulmonary blastoma with surgery, chemotherapy, and radiotherapy.

Severe hypothyroidism caused by hepatic hemangioendothelioma in an infant of a diabetic mother.

Hemangioendotheliomas can express type 3 iodothyronine deiodinase and cause severe hypothyroidism. The risk of congenital malformations such as vertebral and cardiac abnormalities in infants of diabetic mothers is higher than in babies of healthy women. Here we report an infant of a diabetic mother with hypothyroidism caused by liver hemangioendothelioma. Consumptive hypothyroidism should be an indicator to search for a vascular tumor in infants. Supranormal doses of L-thyroxine might be required for normalization of thyroid function until the tumor involutes or is resected.

Late cardiac evaluation of children with solid tumors after anthracycline chemotherapy.

BACKGROUND: The therapeutic potential of anthracycline antibiotics is limited by their cardiotoxicity. Electrocardiography, exercise testing, and two-dimensional echocardiography are non-invasive techniques used in the follow-up of children for cardiotoxicity. Plasma B-type natriuretic peptide (BNP) levels are thought to be useful markers in the early detection of AC induced cardiomyopathy. PROCEDURE: We evaluated cardiac status of 34 patients with solid tumors treated with anthracycline antibiotics. All of the patients were asymptomatic and had no evidence of residual malignancy. They were evaluated by electrocardiography, exercise testing, echocardiography, and plasma BNP levels measured before and after the exercise testing. RESULTS: Electrocardiography revealed only minor abnormalities of little clinical significance. All of the patients completed the exercise testing without complication, and the duration of the exercise for each patient was between normal limits. Cardiac output (CO) and wall stress (WS) were significantly increased in patients, than in controls in echocardiographic evaluation of systolic functions (P < 0.001). Diastolic filling patterns showed various abnormalities; M-E, M-A, T-E, T-A, AT, and IVRT were significantly higher than those of controls. Mean plasma BNP levels of the patients (10.56 +/- 10.22 pg/ml) were significantly higher than BNP levels of the healthy controls (4.09 +/- 2.26 pg/ml) (P < 0.016), before exercise testing. The mean plasma BNP levels of the patients (15.70 +/- 14.06 pg/ml) were higher than resting state after exercise testing, but it was not statistically significant (P > 0.05). CONCLUSION: Our findings demonstrated that echocardiographic and biochemical abnormalities could be found even at low cumulative doses of AC antibiotics. The use of serial echocardiographic studies and plasma BNP determinations to identify high-risk patients for cardiotoxicity needs to be verified by additional studies.

Second primary myogenic sarcoma in a patient with bilateral retinoblastoma.

Retinoblastoma is the primary ocular malignancy affecting children under 6 years of age. The development of second malignant tumors in survivors of hereditary retinoblastoma is a well-known clinical entity and a major cause of morbidity and mortality. Rhabdomyosarcomas as second primary tumors have been only rarely described. The authors report a patient with bilateral retinoblastoma who developed a myogenic sarcoma of the orbit after 5.5 years of diagnosis. The short latency period may be explained by tumor histology with the contribution of radiotherapy and chemotherapy. The prognosis of second tumors is poor despite aggressive treatment.