Early pharmacokinetics and clinical effects of oral D-amphetamine in normal subjects

Seven normal subjects received 0.25 mg/kg D-amphetamine orally, both after an overnight fast and again after a standard breakfast. Plasma levels, subjective and cardiovascular effects, and observer-rated activation were assessed hourly for 5 hr. Food did not affect amphetamine levels. Plasma levels peaked at 2-3 hr. Maximum cardiovascular effects generally occurred at 1 hr, whereas maximum behavioral and subjective effects occurred at 2 hr. Subjective and behavioral effects declined thereafter, in spite of substantial amphetamine levels. A separate group of 8 subjects received 0.5 mg/kg D-amphetamine orally. Plasma levels, subjective and cardiovascular effects, and activation ratings were assessed hourly for 4 hr. Maximum plasma levels were approximately twice those seen in the first group. In this case, plasma levels peaked at 3-4 hr; blood pressure and subjective and behavioral effects were all maximal at 2-3 hr and were declining by 4 hr, in spite of stable or rising plasma levels.     

A phase I/II study of continuous infusion suramin in patients with hormone-refractory prostate cancer : toxicity and response

 Introduction: Suramin is a synthetic polysulfonated naphthylurea which has been used for the treatment of African trypanosomiasis and onchocerciasis, but since the mid-1980s has received attention as a possible antiretroviral and antineoplastic agent. Objective: This clinical trial of suramin was undertaken as a phase I/II study in patients with hormone-refractory prostate cancer, with the hypothesis that the intensity of therapy with suramin could be increased significantly if measures were undertaken to maintain the plasma concentrations of the drug under 300 μg/ml. Methods: We report the clinical results of this trial, wherein patients were treated at three different targeted plasma suramin concentrations (275, 215 and 175 μg/ml) for varying periods of time (2, 4 or 8 weeks), with delivery of the drug by continuous intravenous infusion. Results: The major toxicity observed in this trial was neurologic, consisting of a motor and sensory peripheral neuropathy that resulted in both paresis and paralysis of the limbs. Nearly all of this severe (CTEP grade III, IV) neurologic toxicity was observed in the patients treated at a plasma suramin concentration of 275 μg/ml for 4 or more weeks. A single patient treated at 215 μg/ml for 8 weeks developed moderate (CTEP grade III) proximal lower extremity weakness, and no patient treated at 175 μg/ml developed this toxicity. The second most common toxicity observed was infection of the central venous catheter. The overall response rate for all of the evaluable patients was 17% (13 of 75 patients). In addition, prostate-specific antigen (PSA)-defined responses were observed in six patients receiving therapy at 175 μg/ml, but these responses were confounded by cessation of therapy with flutamide during suramin treatment. Conclusions: In summary, although plasma suramin concentrations were maintained below 300 μg/ml, neurologic toxicity nonetheless occurred with high frequency in patients treated at 275 μg/ml for 4 or more weeks. Therapy at 215 and 175 μg/ml was in general well tolerated, but central venous catheter-related infection, as well as the inconvenience and expense of continuous infusional therapy, make this method of drug delivery impractical. Only moderate antitumor activity was observed during this trial, but it is possible that both continuation of flutamide and flutamide withdrawal during suramin therapy confounded the assessment of suramin’s activity in hormone-refractory prostate cancer. Received: 9 June 1995/Accepted: 18 March 1996     

Ultrastructure changes associated with brain death in the human donor heart

Abstract Electromicroscopic examinations were carried out on 30 myocardial biopsies taken from 22 human donor hearts immediately after excision (prestorage) or immediately before transplantation (post-storage). All electron micrographs were independently examined by two morphologists. Eleven structures were examined in each micrograph, and each structure was scored according to the degree of injury. A good interobserver correlation was obtained in 84 % of the structures scored. In the prestorage left ventricular biopsies ( n = 11), approximately 20 %-25 % showed moderate to severe ultrastructural injury. The ultrastructural injury observed in the poststorage left ventricular biopsies ( n = 15) was no different from that in the prestorage group, particularly injury to the sarcomere and mitochondria. A similar degree and pattern of injury was seen in the right ventricle ( n = 4). There was no evidence that an ischemic storage period of less than 6 h increased the degree of injury seen. However, there was a higher incidence of moderate to severe injury in those hearts excised from donors initially dependent on high inotropic support.     

Dynamic skinfold thickness measurement in infants fed breast-milk, low- or high-sodium formula

A stratified sample of normal infants born at term at Johannesburg Hospital, who attended the hospital for a routine 6-week follow-up visit, were selected to include 43 infants who were exclusively breast-fed, 42 fed a low-sodium formula and 39 fed a high-sodium formula (greater than 10 mmol sodium/l). Dynamic skinfold thickness measurements (DSTM), designed to assess the amount of interstitial fluid, were performed on each infant by the application of a skinfold caliper for a 3-second sampling period at two sites. The curves generated by these applications were recorded and analysed by microcomputer. There were no differences between any of the feeding groups for DSTM measurements of blood pressure suggesting that the range of sodium ingested by these groups of infants had no significant effects on extracellular water content. However, using multiple linear regression, both DSTM and blood pressure were best predicted by body weight and not by age or any other anthropometric measurement. Thus the normal postnatal decrease in extracellular fluid volume and increase in blood pressure appears to be most closely related to an increase in body weight.     

Adopted Children: Core Issues and Unique Challenges

TOPIC: Psychological impact of adoption and resulting core issues for adopted children. PURPOSE: To raise awareness of the psychological impact of adoption. SOURCES: Published literature and personal observations. CONCLUSIONS: Adoption raises unique issues and challenges for the child and adoptive parents. Resolving the issues of adoption is a lifelong process. Through an awareness of the issues inherent in adoption, nurses and parents can use strategies that will enhance children's self-esteem and decrease their emotional vulnerability. Search terms: Adoption, intervention, loss, self-esteem, strategies