Interactive effect of cytochrome P450 17alpha-hydroxylase and dopamine D3 receptor gene polymorphisms on abnormal involuntary movements in chronic schizophrenia.

BACKGROUND: Tardive dyskinesia is a chronic adverse effect of anti psychotic drugs, where association with a polymorphic site in the dopamine D3 receptor gene has been previously reported. Cytochrome P 450 17alpha-hydroxylase activity has been implicated with modulation of central dopamine release as well as neuroprotection. We investigated the association of a T -->C variation in the cytochrome P 450 17alpha-hydroxylase gene with tardive dyskinesia in patients with chronic schizophrenia. METHODS: Cytochrome P 450 17 allele and genotype frequencies were compared between matched schizophrenia patients with (n = 55) or without tardive dyskinesia (n = 58). Interactive effects of cytochrome P 450 17alpha-hydroxylase with the dopamine D3 Ser9Gly polymorphism on abnormal involuntary movements were examined. RESULTS: There was no difference in cytochrome P 450 17alpha-hydroxylase genotype distribution between patients with and without tardive dyskinesia; however, patients carrying the cytochrome P 450 17alpha-hydroxylase A2-A2 genotype and the dopamine D3gly allele had the highest orofacial (p <.04), distal (p <.05), and incapacitation (p <.04) scores on the Abnormal Involuntary Movements Scale. CONCLUSIONS: Schizophrenia patients who carry the dopamine D3gly allele and the cytochrome P 450 17alpha-hydroxylase A2-A2 genotype may be more likely to develop abnormal orofoacial and distal involuntary movements and to be incapacitated by these movements when chronically exposed to classical antipsychotic drugs.     

Stomach cancer occurring after the radiation and chemical therapy of a lymphosarcoma

A case of the development of gastric adenocarcinoma in a woman of 47 who for the previous 9 years had been treated for lymphoplasmocytic lymphosarcoma is described. The patient periodically received courses of polychemotherapy and twice radiotherapy on the stomach area because of the affection of the stomach detected by roentgenological examination and endoscopy with gastrobiopsy. In the past two years the patient underwent multiple endoscopic examinations demonstrating over time the changes in the gastric mucosa which initially showed superficial adenomatous outgrowths of the proliferating epithelium in the presence of marked atrophy and intestinal metaplasia. Gradually the signs of dysplasia increased in them and finally adenocarcinoma was established. Resection of the stomach revealed a highly differentiated adenocarcinoma in the form of an exophytic node 2 x 2 x 1 cm in size growing into the submucous layer.     

High-dose leucovorin reverses acute high-dose methotrexate neurotoxicity in the rat

Intravenous high-dose methotrexate (HD-MTX) reduces cerebral glucose metabolism and produces behavioral abnormalities and electroencephalographic slowing in an animal model of acute HD-MTX neurotoxicity and in cancer patients undergoing HD-MTX chemotherapy. We used our model of HD-MTX neurotoxicity in the rat to determine if leucovorin (5-formyltetrahydrofolate) reduces this neurotoxicity, and extended our characterization of this model to identify regional as well as global HD-MTX treatment effects and to investigate HD-MTX-induced alterations in regional brain pH. Intravenous high-dose leucovorin reversed the HD-MTX-induced decrease in cerebral glucose metabolism and associated behavioral and electroencephalographic abnormalities in the rat, but low-dose leucovorin was ineffective. The major effect of HD-MTX on cerebral glucose metabolism was a global reduction; however, smaller region-specific treatment effects were identified in auditory, thalamic, and white matter structures. HD-MTX did not alter regional brain pH. These findings suggest a potential clinical role for high-dose leucovorin in severe or prolonged acute HD-MTX neurotoxicity and provide an important justification for the role of positron emission tomography in the early detection of clinical HD-MTX neurotoxicity.     

Lead-contaminated house dust and urban children's blood lead levels.

OBJECTIVES: This study assessed the relationship between lead-contaminated house dust and urban children's blood lead levels. METHODS: A random-sample survey was used to identify and enroll 205 children, 12 to 31 months of age, who had resided in the same house since at least 6 months of age. Children's blood and household dust, water, soil, and paint were analyzed for lead, and interviews were conducted to ascertain risk factors for elevated blood lead (> or = 10 micrograms/dL). RESULTS: Children's mean blood lead level was 7.7 micrograms/dL. In addition to dust lead loading (micrograms of lead per square foot), independent predictors of children's blood lead were Black race, soil lead levels, ingestion of soil or dirt, lead content and condition of painted surfaces, and water lead levels. For dust lead standards of 5 micrograms/sq ft, 20 micrograms/sq ft, and 40 micrograms/sq ft on noncarpeted floors, the estimated percentages of children having blood lead levels at or above 10 micrograms/dL were 4%, 15%, and 20%, respectively, after adjusting for other significant covariates. CONCLUSIONS: Lead-contaminated house dust is a significant contributor to lead intake among urban children who have low-level elevations in blood lead. A substantial proportion of children may have blood lead levels of at least 10 micrograms/dL at dust lead levels considerably lower than current standards.     

Leukoencephalopathy following high-dose intravenous methotrexate chemotherapy: Quantitative assessment of white matter attenuation using computed tomography

Summary A clinical or subclinical leukoencephalopathy occurs in some children after treatment of acute lymphatic leukemia with prophylactic cranial radiation therapy and parenteral or intrathecal methotrexate. We have observed a similar clinical leukoencephalopathy in patients with bone tumors treated with intravenous high-dose methotrexate and citrovorum factor without cranial irradiation. CT scans of such patients may indicate decreased white matter attenuation, but visual appraisal of this phenomenon is occasionally misleading. A computerized method for analyzing white matter hypodensity by determining the mean attenuation coefficient for one or several contiguous CT slices has therefore been developed. Serial comparisons of this mean attenuation coefficient appear to be more reliable than simple visual appraisal.     

Effect of selecting a fixed dephosphorylation rate on the estimation of rate constants and rCMRGlu from dynamic [18F] fluorodeoxyglucose/PET data

Several publications have discussed the estimation and physiologic significance of regional [18F]fluorodeoxyglucose (FDG) rate constants and metabolic rates. Most of these studies analyzed dynamic data collected over 45-60 min; three rate constants (k1-k3) and blood volume (Vb) were estimated and the regional cerebral metabolic rate for glucose (rCMRGlu) was subsequently derived using the measured blood glucose value and a regionally invariant value of the lumped constant (LC). The dephosphorylation rate constant (k4) was either neglected, or a fixed value was used in the estimation procedure to obtain the remaining parameters. To compare the rate constants obtained by different authors using different values of k4 is impossible without knowledge of the effect of selecting different fixed values of k4 (including zero) on the estimated rate constants and rCMRGlu. Based on our analysis of FDG/PET data from nine normal volunteer subjects, we conclude that inclusion of a fixed value for k4, in spite of a scaling effect on the absolute values of model parameters, has no effect on the coefficient of variation (CV) of within- and between-subject parameter estimates and glucose metabolic rates.     

Squamous cell cancer of the anal canal

Squamous cell carcinoma of the anal canal is rather rare and amounts to 3.5% of all rectal neoplasms. Though it has a clear-cut clinical picture, 29.5% of patients admitted for specialized treatment suffer from stage IV due to inadequate diagnosis. Surgery is the most effective method of management of squamous cell carcinoma of the anal canal. Radiation therapy may be an adjuvant procedure.     

Angiographic diagnosis and treatment of bleeding by selective embolization following pelvic fracture in children.

Angiography has been used successfully in adults for evaluation following major trauma and to subsequently control hemorrhage associated with pelvic fracture by selective embolization. This report illustrates that the technique is applicable in the evaluation and treatment of children with similar injuries.