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Data on the effect of vitamin E and selenium deficiency on lipid peroxidation in vivo have been limited. F2-isoprostanes are novel prostanoids that, free in plasma and esterified to phospholipids in tissues, are markers of lipid peroxidation in vivo. To address the importance of vitamin E and selenium in defense against lipid peroxidation in vivo, we determined F2-isoprostane concentrations in the plasma and organs of rats fed diets deficient in one or both nutrients. Weanling rats were fed a vitamin E- and selenium-deficient diet for 12 wk and then divided into four groups. One group continued to receive the doubly deficient diet, and the other three groups were fed the diet supplemented with vitamin E, selenium or both nutrients (control diet) for 4 wk. Plasma F2-isoprostanes in rats fed the doubly deficient diet were 5.2-fold higher than in animals changed to a control diet. In addition, there were significant differences in liver, lung, kidney, heart and skeletal muscle phospholipid-esterified F2-isoprostanes between these two groups. Lesser increases were noted in the group fed the vitamin E-deficient diet. Selenium deficiency alone was not associated with greater lipid peroxidation. Lipid peroxidation occurs in tissues of rats fed a vitamin E-deficient diet and is increased by concomitant selenium deficiency.
OBJECTIVE - To investigate first trimester nuchal translucency > or = 3 mm as a screening test for aneuploidy in the normal pregnant population.
DESIGN - A pilot observational study.
SETTING - University College Hospital, London.
SUBJECTS - One thousand one hundred and twenty-seven women had measurements of nuchal translucency at the time of their dating scan (8-13 weeks of gestation).
RESULTS - Seventy fetuses (6%) had a nuchal translucency > or = 3 mm. Five karyotypically abnormal fetuses were identified by standard routine techniques (three trisomy 21, two trisomy 18), all in high risk mothers (> or = 39 years). Only two had nuchal translucency > or = 3 mm (one trisomy 21, one trisomy 18).
CONCLUSIONS - Although nuchal translucency measurement is feasible and promising, there is at present insufficient data to warrant its introduction for screening of the general population, or to replace traditional second trimester screening.
It has been proposed that a defect in tocopherol transport may lead to a chronic vitamin deficiency in Duchenne muscular dystrophy (DMD). To test this hypothesis, a pilot clinical trial which involved the infusion of tocopherol-laden plasma was carried out. An increased uptake of tocopherol into erythrocyte membranes during infusions failed to produce a significant reduction in plasma enzyme levels or to arrest the dystrophic process in the two children examined. Further studies to investigate treatments with increased amounts of tocopherol, in conjunction with other antioxidants, may prove a more fruitful avenue of research.
In an effort to augment public awareness of the benefits of screening mammography and to encourage the use of screening mammograms, the Tennessee Division of the American Cancer Society initiated the Breast Cancer Detection Awareness Program in March 1988. As a result of the initiative, 3,473 women telephoned for information, and 3,123 were found to be eligible for a screening mammogram. Of the 2,248 mammograms actually obtained, 1,764 (78%) were interpreted as normal, whereas 484 (22%) were classified as abnormal. Of the 484 women with abnormal mammograms, 277 (57%) were advised to have follow-up mammograms and 57 (12%) had excisional biopsy. The 55 biopsies reported showed benign changes in 83.6% and malignancy in 16.4%. Thus, nine malignancies were discovered from 2,248 screening mammograms (four malignancies per 1,000 mammograms). No malignancies were found in women between 35 and 39 years old.
In the present study, intellectually precocious and average ability youths performed a dichotic listening task (Experiment 1) and a free-vision chimeric face task (Experiment 2). Patterns of hemispheric lateralization and the relative involvement of the left and right hemispheres during cognitive processing were assessed. In Experiment 1, the average ability youths demonstrated a right ear/left hemisphere (re/LH) superiority for identification of CV syllables, while the gifted subjects failed to show any ear/hemisphere advantage. In Experiment 2, members of both groups tended to judge the leftside smile/rightside neutral half-faces as "happier", a pattern indicative of enhanced right hemisphere (RH) arousal. Notably, the degree of RH involvement was significantly greater in the gifted as compared to average ability youths. Moreover, laterality scores of the precocious on the chimeric face task correlated with their performance on the College Board Scholastic Aptitude test (SAT), i.e. the greater the leftward bias, the higher the SAT score. These findings, taken in composite, suggest that a high level of RH involvement during cognitive processing may be related to intellectual precocity.
Preliminary studies involving small numbers of patients have suggested that interleukin-2 (IL-2) administered by continuous infusion in repetitive weekly cycles using doses of 3 x 10(6) U/M2/day is immunologically active and can induce tumor responses in patients with renal cell carcinoma. This study was designed to examine both the immunological and clinical effects of prolonged infusion IL-2 given by repetitive weekly cycles; first at moderate doses for 4 weeks as an impatient followed by lower doses of IL-2 for up to 5 months. Prolonged IL-2 treatment was investigated because previous studies revealed that patients had a return to their baseline immune status within 4 weeks after completing IL-2 treatment. Twenty-five patients (including 18 with renal cell carcinoma) were treated with one of two regimens utilizing IL-2 as sole therapy. These regimens were designed to induce augmented and prolonged immune activation based upon in vitro and in vivo data. Though patients on both arms of the study demonstrated sustained lymphocytosis, increase in numbers of natural killer cells, and induction of lymphokine-activated killer activity with prolonged IL-2 administration, only 1 out of the 18 patients with renal cell carcinoma demonstrated a sustained partial antitumor response to therapy. Furthermore, several patients demonstrated profound immune activation, without any evidence of tumor regression. The lack of clinical responses in these patients showing marked activation of LAK cytotoxicity suggests that other variables must also influence the likelihood of antitumor effects for patients receiving IL-2 therapy.
Administration of recombinant human growth hormone stimulates protein synthesis, decreases urea generation, and improves nitrogen balance in individuals with normal renal function. However, little information is available concerning the effects of growth hormone in patients with renal disease. This pilot study evaluated urea kinetics and clinical/metabolic responses to short-term growth hormone administration in five clinically stable adult patients requiring maintenance hemodialysis for end-stage renal failure. The dialysis prescription, medications, and oral calorie and protein intake of each patient remained constant during an initial control week and a subsequent 2-wk growth hormone treatment period. During treatment, growth hormone (5 or 10 mg) was administered s.c. immediately after each dialysis session. Protein and calorie intake, vital signs, body weight, and other clinical parameters remained stable throughout the 3-wk study. BUN values fell significantly (approximately 20 to 25%) during growth hormone administration compared with control week values. Similarly, urea kinetic modeling demonstrated a significant reduction in urea generation and the protein catabolic rate during each week of growth hormone treatment. Plasma insulin-like growth factor I levels rose significantly, and serum phosphorus and intact parathyroid hormone levels fell significantly during growth hormone administration. Serum glucose and other blood values remained stable. This preliminary study suggests that growth hormone administration reduces urea generation and improves the efficiency of dietary protein utilization in stable adult hemodialysis patients. Growth hormone may be a useful adjunctive therapy to diminish body protein catabolism in this patient population.
Twenty-eight patients with unresectable, metastatic non-small cell lung cancer (NSCLC) were treated with carboplatin/oral etoposide. Carboplatin was administered intravenously on day 1 at a dose of 300 mg/m2 (12 patients) or 350 mg/m2 (16 patients); oral etoposide was administered at a dose of 50 mg/m2/d for 21 consecutive days. Treatment was repeated every 28 days. Patient characteristics included male:female ratio of 23:5, median age of 60 years, median Eastern Cooperative Oncology Group performance status of 1, weight loss of 5% or more in seven patients; stage IIIB disease in two patients and stage IV in 26. Twenty-five patients were evaluable for response and seven (28%) achieved a partial response (95% confidence interval, 14% to 48%). Median duration of response was 3+ months (range, 2+ to 6+) and median survival was 4+ months (range, 1+ to 10+). Myelosuppression was the predominate toxicity; leukocyte and platelet nadirs occurred between days 22 and 29, with median counts of 2,900/microL and 172,000/microL, respectively. The median interval between the start of cycle 1 and the start of cycle 2 was 33 days (range, 26 to 42). Carboplatin/oral etoposide is a moderately active regimen against advanced NSCLC that can be administered in an outpatient setting with manageable toxicity. Its impact on survival remains to be determined.