Pharmacokinetics of 2-chlorodeoxyadenosine in a child undergoing hemofiltration and hemodialysis for acute renal failure

The clearance of 2-chlorodeoxyadenosine (2-CdA) in patients with renal insufficiency has not been characterized previously. The authors describe the clinical course and the pharmacokinetics of 2-CdA in a child with acute monoblastic leukemia who experienced acute renal failure during treatment with cytarabine and 2-CdA. 2-CdA (9 mg/m per day) was infused over 30 minutes daily for 5 days. Plasma and dialysate concentrations of 2-CdA were measured by high-performance liquid chromatography. The rate of this patient's 2-CdA clearance was lower than the rates reported for children with normal renal function. The average clearance rate, reflecting systemic clearance and clearance by continuous venovenous hemofiltration and hemodialysis, was 12.4 L/hour per m for the first 3 days of 2-CdA therapy. He did not experience untoward hematologic toxicity. Because high 2-CdA plasma concentrations were observed in this patient, clinicians are advised to exercise caution when using this drug in patients with renal dysfunction. More experience in the administration of 2-CdA to patients with renal insufficiency will be necessary to determine the need for dosage adjustment.     

Probing biotransformation relationships among pyridoacridines by focusing on oxygenated analogues

The presence of the MeO-5 in the structure 5-methoxyamphimidine (5) is unusual in the light of a recent analysis of the relationships among sponge- and tunicate-derived pyridoacridines. We explore a possible biochemical pathway, from neoamphimidine (2) to 5-methoxyamphimidine (5). The results of semiempirical and ab initio calculations are presented to help understand the relationships that favor the formation of 5 versus the formation of undiscovered bis-oxygenated pyridoacridines.     

Structures and cytotoxic properties of trichoverroids and their macrolide analogues produced by saltwater culture of Myrothecium verrucaria

Saltwater culture of Myrothecium verrucaria, separated from a Spongia sp. collected in Hawaii, was a source of three new trichothecenes, 3-hydroxyroridin E (1a), 13'-acetyltrichoverrin B (2), and miophytocen C (3) and nine known related compounds (1b, 4, 5, 6, 7a, 7b, 8, 9a, and 9b). The stereostructures of the new compounds were established on the basis of 1D and 2D NMR spectral analyses and a chemical transformation. At the same time, the stereostructures of known compounds, 1b, 4, and 5 reported previously were also elucidated. All the compounds except 3 showed significant cytotoxicity against murine and human tumor cell lines. Moreover, the structure-activity relationships (SARs) were established from the results of the bioassay data.     

Randomised controlled trial of prophylactic etamsylate: follow up at 2 years of age

AIM: To assess the role of etamsylate in reducing the risk of haemorrhagic brain damage and its consequences. DESIGN: Follow up of babies recruited into a randomised controlled trial. METHODS: A total of 334 infants born before 33 weeks gestation in France and Greece were randomly allocated within the first four hours of birth either to receive etamsylate or to act as controls. The principal outcomes in the trial were death or impairment and/or disability at the age of 2 years. RESULTS: Fifty nine children were lost to follow up. A total of 115 (34%) either died or had some impairment or disability, and 88 (26%) either died or had severe impairment or disability at 2 years of age. These outcomes did not differ significantly between the two randomised groups: relative risks and 95% confidence intervals 1.14 (0.78 to 1.4) and 1.17 (0.82 to 1.68) respectively. The findings were similar for all the prespecified subgroup analyses stratified by key prognostic factors at trial entry: country of birth, gestational age < or >or= 29 weeks, inborn or outborn, age < or >or= 1 hour, and with or without cerebral scan abnormality. CONCLUSION: These findings do not support the use of etamsylate. Other strategies need to be evaluated for the prevention of mortality and morbidity in these vulnerable infants.     

Refeeding the patient with anorexia nervosa

Successful treatment of persons with anorexia nervosa is possible when a multidisciplinary team consisting of a mental health professional, a dietician, and a medical professional with expertise in eating disorders direct treatment. One of the primary goals of treatment is the restoration of weight. Refeeding by oral, enteral, or parenteral routes is a cornerstone of treatment but must be under-taken with care in order to avoid the widespread dysfunction associated with the refeeding syndrome.     

Sex reversal effects of environmentally relevant xenobiotic concentrations on the red-eared slider turtle, a species with temperature-dependent sex determination

Xenobiotics suspected of being estrogenic-the PCB aroclor 1242 and the pesticides toxaphene, dieldrin, p,p'-DDD, cis-Nonachlor, trans-Nonachlor, p,p'-DDE, and chlordane-were examined for their ability to override a male-producing incubation temperature and result in female hatchlings in the red-eared slider, a turtle with temperature-dependent sex determination. Compounds were assayed in the environmentally relevant concentrations detected in alligator eggs from Lake Apopka, Florida, singly, in concert with one another, and with estradiol. Compounds assayed alone and resulting in significant sex reversal were trans-Nonachlor, cis-Nonachlor, aroclor 1242, p,p'-DDE, and chlordane. When administered with estradiol, only one of the compounds, chlordane, caused sex reversal at significant levels. When applied together, however, the eight compounds assayed resulted in significant sex reversal.     

Scales for the measurement of attitudes toward blood donation

Attitudes toward blood donation are frequently assumed to vary along a single dimension from unfavorable to favorable. In contrast, theories of attitude structure specify three distinct attitude components: affect, cognition, and behavior. This article describes the development of three new scales for the measurement of affective, cognitive, and behavioral components of attitudes toward blood donation. The scales were developed using the method of equal-appearing intervals and were administered to both donors of blood and nondonors. Correlations among the scales were relatively small and supported the three-component distinction. Affect was more strongly correlated with the number of prior donations than was cognition, which suggested an important role for emotional factors in blood donation. Scores on all three scales showed the attitudes of blood donors to be more favorable than those of nondonors.