Extremely skewed X-chromosome inactivation patterns in women with recurrent spontaneous abortion

BACKGROUND: The role of extremely skewed X-chromosome inactivation (XCI) has been questioned in the pathogenesis of recurrent spontaneous abortion (RSA) but the results obtained were conflicting. AIMS: We therefore investigated the XCI patterns in peripheral blood DNA obtained from 80 patients who had RSA and 160 age-matched controls. METHODS: Pregnancy history, age, karyotype, and disease information was collected from all subjects. The methylation status of a highly polymorphic cytosine-adenine-guanine repeat in the androgen-receptor (AR) gene was determined by use of methylation-sensitive restriction enzyme HpaII and polymerase chain reaction. RESULTS: Skewed XCI (> 85% skewing) was observed in 13 of the 62 patients informative for the AR polymorphism (20.9%), and eight of the 124 informative controls (6.4%) (P = 0.0069; chi2 test). More importantly, extremely skewed XCI, defined as > 90% inactivation of one allele, was present in 11 (17.7%) patients, and in only two controls (P = 0.0002; chi2 test). CONCLUSIONS: These results support the interpretation that disturbances in XCI mosaicism may be involved in the pathogenesis of RSA.     

Vincristine-induced peripheral neuropathy and urinary bladder paralysis in a child with rhabdomyosarcoma

Vincristine commonly induces peripheral neuropathy but rarely causes voiding dysfunction. In this report, we describe a case of neurogenic bladder and peripheral neuropathy caused by the neurotoxic effect of vincristine and documented by urodynamic testing and electromyography. Neurologic evaluation aided in monitoring and understanding this problem.     

REFRACTORINESS TO RITUXIMAB MONOTHERAPY IN A CHILD WITH RELAPSED/REFRACTORY BURKITT NON-HODGKIN LYMPHOMA

The authors describe a 6-year-old boy diagnosed with mediastinal Burkitt lymphoma with tumor invasion into bone marrow and both kidneys. After receiving chemotherapy according to NHL BFM-95 protocol for the high-risk disseminated lymphoma, the patient reached complete remission. He relapsed in the mediastinum at 5 months from the diagnosis. He underwent thoracotomy and tumor mass was removed by inferior lobectomy of right lung. Residual tumor progressed rapidly. Autologous stem cell transplantation could not be performed because of unresponsiveness to cytoreductive chemotherapy. Twenty-three days after the last chemotherapy course, he received rituximab at a dose of 375 mg/m ² by intravenous infusion weekly, for a total of 8 dose. However, multiple intra-abdominal metastatic lesions were detected at the end of the therapy. Palliative radiotherapy was applied to these sites. He died because of disease progression, 11 months after the diagnosis.     

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.     

ARM ANTHROPOMETRY IN EVALUATION OF MALNUTRITION IN CHILDREN WITH CANCER

Malnutrition in children with cancer is reported to be relatively uncommon at the time of diagnosis. However, in most studies nutritional status measurement has relied almost exclusively on weight-related indices. This can be misleading, because in children with malignancy, tumor masses can reach more than 10% of total body weight. A controlled study was performed in 62 patients using arm anthropometry to provide a more accurate evaluation of the nutritional status of children with cancer at presentation. Height, weight, midupper arm circumference (MUAC), and triceps skinfold thickness (TSFT) were measured in all patients (40 boys, 22 girls) and controls (18 boys, 13 girls). Weight for height (W FH) of each patient was compared with the national standards. MUAC and TSF T were also interpreted according to the standards developed by A. Roberto Frisancho. The mean ages were 6.5 3.7 years (range 0.08-13) and 5.7 4.7 years (range 0.25-15) in patients and control group, respectively. Results showed that although the W FH values for patients were normal, MUAC and TSF T values were significantly less than control values (P < 0.001). Moreover, 27% of patients showed malnutrition (they had MUAC and TSF T below 5th percentile). Patients with intraabdominal solid tumors had significantly lower MUAC and TSF T values than those with extraabdominal solid tumors (P < 0.05). The data strongly indicate that malnutrition is common at the time of diagnosis in children with cancer, and arm anthropometry should replace the use of weight-related indices to identify malnutrition in children.