Changes in regional cerebral blood flow during brain maturation in children and adolescents.

Regional cerebral blood flow (rCBF) was studied by SPECT using 133Xe in 42 children, aged 2 days to 19 years, considered as neurologically normal. rCBF was measured on cortical regions and on the cerebellum and thalamus. Curves for reference values and standard deviation were defined for each region. At birth, cortical rCBFs were lower than those for adults; after birth they increased until 5 or 6 yr of age to values 50%-85% higher than those for adults and thereafter decreased, reaching adult levels between 15 and 19 yr. Neonatal values of rCBF on cerebellum and thalamus were slightly higher than adult level, but not significantly; after age 1, they followed the common pattern for cortical curves. When rCBFs were expressed in percent global CBF, they were lower at birth than adult levels in the cortex, then increased and reached a plateau corresponding to the adult value before the second year of age. The time needed to reach normal adult values differed for each cortical region. The shortest time was found on the primary cortex and the longest on the associative cortex. Cognitive development of the child seems to be related to changes in blood flow of the corresponding brain regions.     

Stimulation of tumor growthin vitro andin vivo by suramin on the VX2 model

Suramin is an antitrypanosomal compound with confirmed efficacy against several human malignancies. It is generally assumed that its mechanism of action includes the interaction with different growth factors, unlike most of the anticancer drugs. Its anticancer activity has not been testedin vivo against squamous cell carcinoma. The purpose of this study was to assess the efficacy and toxicity of suraminin vivo andin vitro on the VX2 tumor model at therapeutic monitored plasma concentrations. We determined the pharmacokinetics of suramin in rabbits, and modelized its administration in order to obtain plasma concentrations between 150 and 300 μg/ml throughout the treatment course of 3 weeks. Under these conditions, antitumor effects of suramin were evaluatedin vivo by comparing liver tumor involvement in suramin-treated and control rabbits. Liver involvement was quantified by image analysis andin vitro effects were also determined at the same concentrations.In vivo, suramin promoted liver tumor growth significantly (p<0.05), compared to untreated controls.In vitro, suramin significantly stimulated tumor cell growth at concentrations above 200 μg/ml (p<0.01). Suramin may have stimulatory effects on tumor growth in squamous cell carcinoma at relevant plasma drug concentrations. Caution should be taken in further trials in patients with squamous cell carcinomas.     

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Thymidylate synthase activity,folates, and glutathione system in head and neck carcinoma and adjacent tissues

Background. Head and neck squamous cell carcinomas (HNSCC) present variable aggressiveness and chemosensitivity. Because the glutathione (GSH) system and thymidylate synthase (TS) are involved in the resistance to the main drugs used in HNSCC (cisplatin and 5-FU), we studied these systems in tumors and normal mucosae. Methods. Tumor samples and normal adjacent mucosae were collected from 37 untreated HNSCC patients. GSH and glutathione S-transferase (GST) activity were assayed by spectrophotometry, whereas TS activity and folates were determined by radioassays. Results. Mean GSH levels were higher in tumors (15.2 ± 8.2 nmol/mg protein) than in mucosae (8.3 ± 4.1 nmol/mg protein) (p = 0.005, paired t test). GST activity was also higher in tumors (394 ± 194 nmol/min/mg protein) than in mucosae (261 ± 132 nmol/min/mg protein) (p = 0.0003). TS activity was markedly higher in tumors (9.2 ± 21.5 pmol/min/mg protein) compared to that of mucosae (0.9 ± 1.2 pmol/min/mg protein) (p = 0.0001). Folate levels in tumors and mucosae were similar (1.2 ± 1.1 and 0.8 ± 0.9 pmol/mg protein, respectively; p = 0.1, NS). In relation to clinical stage and tumor size, a statistical difference was found in GSH and GST values between tumors and mucosae for stage IV and T3/T4. The increase in tumor TS compared to that of mucosae was significant for all clinical stages, tumor sizes, and nodal involvement. Conclusions. These data enhance our understanding of the enzymatic systems involved in cisplatin and 5-fluorouracil (5-FU) resistance in HNSCC and normal mucosae and may help to elucidate tumor behavior and interpatient differences in drug sensitivity. © 1994 John Wiley & Sons, Inc.     

Combined mortality and morbidity of direct surgical treatment of abdominal aortic aneurysm

Two hundred aneurysms of the abdominal aorta were treated surgically from 1980 to 1987 by the same surgeon. There were 187 men and 13 women whose mean age was 66.1 years. Nine patients were 80-years-old or more. Eighty-seven percent of patients had preoperative risk factors, 30% of which were coronary artery disease. The operative approach was through a transverse laparotomy in 188 patients compared to 11 midline incisions and one lumbotomy. An aortoaortic tube was inserted in 87 patients, a bifurcated prosthesis in 99, and a tube bypass in 14. Five patients (2.5%) died within the 30 day perioperative period. Death was due to colonic necrosis, right heart chamber thrombosis, renal failure after repeat operation for acute lower limb ischemia, and myocardial infarction associated with renal and respiratory failure. The morbidity rate was 15.7% (31 patients) and included seven neurologic accidents, four respiratory complications, five ischemic events of the lower limbs requiring reoperation and one amputation, four cardiac complications, two renal failures, one reversible colonic ischemia, one revision for incomplete hemostasis, one phlebitis, one sliding syndrome, and five minor infections or cutaneous complications. Mean duration of hospital stay was 10.9 days. These results confirm that direct operation on aortic aneurysms can be performed in patients from all age groups and even with associated diseases. A rapid, simple technique based on a transverse approach, minimal dissection and insertion of aortoaortic tubes, whenever feasible, appears to reduce combined mortality-morbidity.Presented at the Annual Meeting of the Societé de Chirurgie Vasculaire de Langue Française, May 20–21, 1988, La Grande Motte, France.     

The 21-aminosteroid antioxidant, U74389F, prevents estradiol-induced depletion of hypothalamic β-endorphin in adult female rats

A single intramuscular injection of 2 mg estradiol valerate (EV) results in neuronal degeneration and β-endorphin depletion in the hypothalamic arcuate nucleus of adult female rats. We have hypothesized that peroxidase-positive astrocytes in this brain region oxidize estrogens and catecholestrogens to semiquinone radicals which mediate oxidative neuronal injury. In the present study, dietary administration of the potent antioxidant 21-aminosteroid, U-74389F, completely blocked EV-induced β-endorphin depletion in the hypothalami of adult female rats. Neither EV nor 21-aminosteroid treatment had any effect on hypothalamic concentrations of neuropeptide Y and Met-enkephalin, confirming that the estradiol lesion is fairly selective for the β-endorphin cell population. The present findings support the hypothesis that the toxic effect of estradiol on hypothalamic β-endorphin neurons is mediated by free radicals.     

Does exposure to infectious diseases in infancy affect old-age mortality? Evidence from a pre-industrial population

Many studies have shown that health conditions experienced in childhood play an important role on an individual's adult mortality. Recent research suggests that past reductions in early life exposure to infectious diseases have been a major contributor to the historical decline in old-age mortality. Drawing on French-Canadian data from cohorts born in the 17th and 18th centuries, we test whether a progressive deterioration in early life conditions (as revealed by an increasing infant mortality rate) translates into a decrease in survival prospects in late life. We use traditional demographic measures such as the age-specific probability of death, and a series of proportional hazard models to control for familial and environmental conditions. Results point toward little evidence of any early life effects. The trend of increasing infant mortality does not correlate with a general increase of mortality in older ages within the same cohorts. Period changes affecting survival at older ages (war, epidemics) as well as demographic and biological characteristics shared within families have a much larger role in old-age mortality than early life characteristics shared within the same cohorts.