Cisplatin disposition in children and adolescents with cancer

Summary The disposition of cisplatin was evaluated in 28 children and adolescents with cancer, as part of a phase II clinical trial. Patients received either 30 mg/m² (11) or 90 mg/m² (17) of cisplatin as a 6-h IV infusion. Serum samples and divided urine collections were obtained over 48 h following completion of the cisplatin infusion, and were assayed in duplicate for total platinum by atomic absorption spectrophotometry. Serum samples obtained up to 4 h after three cisplatin infusions were assayed for parent (free) cisplatin following ultrafiltration. The mean (±SE) elimination half-life of free cisplatin in serum was 1.3 (±0.4) h. Serial serum concentrations of total platinum following 90 mg/m² dosages were adequately described by a biexponential equation. The mean (±SE) serum T_1/2 of total platinum was 0.42 (±0.10) h and the mean (±SE) T_1/2 was 44.43 (±8.24) h. The intercompartment distribution rate constants of a two-compartment kinetic model indicate extensive tissue accumulation of total platinum, with a rate of transport into tissue compartments (K₁₂) that is about six times the rate of transport out of tissues (K₂₁). The mean (±SE) renal clearance of total platinum from 0–3 h was 37.36 (±11.96) ml/min/m² and 35.8 (±13.6) ml/min/m² for the 30 mg/m² and 90 mg/m² groups, respectively. This value decreased to 3.25 (±0.94) and 2.16 (±0.4) ml/min/m² for the two groups by the 6–12 h interval, and remained between 1 and 3 ml/min/m² for the duration of the observation period. The ratio of total plantinum clearance to creatinine clearance decreased significantly(P<0.05) beginning 3 h post-infusion. The change in renal clearance of total platinum is apparently a function of two independent first-order processes for renal clearance of parent drug and cisplatin metabolites.     

Comparison of thyrotropin-releasing hormone with melanocyte-stimulating-hormone-release-inhibiting factor as pentobarbital antagonists in monkeys

Thyrotropin-releasing hormone (TRH), 0.1 mg/kg, i.m., significantly counteracted pentobarbital narcosis in six monkeys, but melanocyte-stimulating-hormone-release-inhibiting factor (MIF), 0.1 mg/kg i.m., did not. Earlier dose-response studies in unanesthetized monkeys had shown that this dose of MIF stimulated motor activity; this dose of TRH had shown no stimulant effect, but a higher dose depressed activity. Thus, an MIF dose that stimulates unanesthetized monkeys does not reverse pentobarbital narcosis; a TRH dose that by itself is neither stimulant nor depressant does partially reverse pentobarbital narcosis.     

The influence of pregnancy and gender on perivascular innervation of rat posterior cerebral arteries

The authors investigated the influence of pregnancy and gender on the density of trigeminal and sympathetic perivascular nerves in posterior cerebral arteries (PCA) and the reactivity to norepinephrine and calcitonin gene-related peptide (CGRP). PCAs were isolated from nonpregnant, late-pregnant, postpartum, and male rats, mounted and pressurized on an arteriograph chamber to obtain concentration-response curves to norepinephrine and CGRP. Arteries were immunostained for CGRP-, tyrosine hydroxylase-, and protein gene product 9.5 (PGP 9.5)-containing perivascular nerves, and nerve density was determined morphologically. Pregnancy had a trophic effect on trigeminal perivascular innervation (P < .01 vs male); however, this was not accompanied by a change in reactivity to CGRP. Sympathetic and PGP 9.5 nerve densities were not altered by pregnancy or gender, and there were no differences in reactivity to norepinephrine. Together, these results suggest that the increase in trigeminal innervation during pregnancy is more related to nociception than in controlling resting cerebral blood flow.     

Efficient purification of the biosurfactant viscosin from Pseudomonas libanensis strain M9-3 and its physicochemical and biological properties

Viscosin (1), an effective surface-active cyclic lipopeptide, was efficiently recovered from Pseudomonas libanensis M9-3 with a simple purification protocol. A major pigment also obtained during this process was identified as phenazine-1-carboxylic acid. The critical micelle concentration (cmc) of viscosin was determined to be 54 mg L (-1), and the minimum surface tension between air and water at the cmc was 28 mN m (-1). Viscosin forms stable emulsions even at low concentrations (7.5 mg L (-1)), and the conditional stability constant for a cadmium-viscosin complex was determined to be 5.87. The physicochemical properties measured for viscosin are similar to other well-studied biosurfactants such as rhamnolipid and surfactin. Viscosin inhibited migration of the metastatic prostate cancer cell line, PC-3M, without visible toxicity. These properties suggest the potential of viscosin in environmental and biomedical applications.     

Physical injury from intimate partner violence: measurement strategies and challenges

Physical injury that occurs as a result of intimate partner violence needs to be treated to relieve pain, promote healing, and prevent infection. Detection of physical injury is an important component of the forensic examination because of its role in criminal justice proceedings. Better detection and measurement techniques are needed to quantify physical injuries and advance the science. This article addresses current practices of injury identification, challenges in injury measurement, and future directions for research.     

Prospective parents' intentions regarding disclosure following the removal of donor anonymity

This short survey of UK infertility counsellors was designed to determine whether the removal of donor anonymity resulted in noticeable changes in prospective parents' stated intentions regarding disclosure of their origins to any children conceived through donor conception. Members of the British Infertility Counselling Association working in Human Fertilisation and Embryology Authority (HFEA) -- licensed centres, before and after the legal changes, were sent a short questionnaire that included space for free comments (take-up: 62%). Three-quarters reported changes. Of these, two-thirds said prospective parents were more likely to say they would disclose, while less than a tenth said prospective parents were less likely do so. Where no changes were noted, this was primarily because the majority of prospective parents had stated their intention to be open even prior to the legal changes. Possible influences on intentions included: the culture within the centre, moves towards openness within the wider society, and parents' lack of confidence regarding how to go about disclosure. Follow-up studies are needed to improve understanding of whether influences on decision making carry through to patterns of actual disclosure; whether involvement in counselling affects outcomes; and whether access to professional assistance at the time of planned disclosure is helpful.     

New guidelines for maternal and neonatal resuscitation

New evidence has prompted changes in our national cardiopulmonary resuscitation guidelines for both neonates and adult patients. The purpose of this article is to provide an overview of the changes recommended by the American Heart Association, Academy of American Pediatrics, and the American College of Obstetrics and Gynecology. In addition, a strategy for implementing these guidelines into practice is suggested.     

Home parenteral nutrition: does affiliation with a national support and educational organization improve patient outcomes?

BACKGROUND: For patients receiving home parenteral nutrition (HPN), catheter-related bloodstream infection (CRBSI) and reactive depression may significantly impact quality-of-life. This study evaluated the influence of patient affiliation with a national organization promoting HPN education and peer support on these outcome variables. METHODS: Using a case-control design, we compared 2 groups of affiliated patients with nonaffiliated controls, who were matched for diagnosis, HPN duration, sex, and age. Group 1 data were obtained from patients in large HPN medical practice programs. Group 2 data were obtained from patients in small medical practices with a small number of HPN patients. All participants were evaluated by structured interviews every 6 months over 18 months. RESULTS: In both data collection groups, affiliated patients (A) had significantly higher (mean +/- SD) quality-of-life scores compared with nonaffiliated patients (NA): (Gr 1: A, 19.8 +/- 4.7 versus NA, 17.6 +/- 5.6, p = .05; Gr 2: A, 20.4 +/- 5.2 versus NA, 17.3 +/- 4.8, p = .05). Affiliated patients also had lower depression scores (Gr 1: A, 10.9 +/- 10.4 versus NA, 20.4 +/- 13.6, p = .01; Gr 2: A, 12.5 +/- 9.6 versus NA, 18.5 +/- 10.8, p = .03) and a lower incidence of catheter-related infections (Gr 1: A, 0.10 +/- 0.3 versus NA, 0.60 +/- 0.55, p = .01; Gr 2: A, 0.27 +/- 0.55 versus NA, 0.71 +/- 0.64, p = .02) than nonaffiliated patients. CONCLUSIONS: Affiliation with an organization that provides ongoing HPN education and peer support was associated with significantly better HPN outcomes. Alternative explanations are discussed in relation to limitations of the case-control design.