Late effects of treatment for Wilms' tumor. A report from the National Wilms' Tumor Study Group.

The National Wilms' Tumor Study (NWTS) was initiated in 1969. One of its objectives was to modulate treatments according to risk factors to minimize the number and severity of treatment-related short-term and long-term iatrogenic complications. The NWTS has therefore incorporated a Long Term Follow-up Study (LTFS) within its framework to monitor late effects. The LTFS is confined to relapse-free survivors alive 5 years or longer after initial surgery, and data are collected using specifically designed forms. A total of 787 patients registered on NWTS-1 or NWTS-2 (1969 to 1979) were eligible, of whom 680 (86%) were available for analysis regarding musculoskeletal, cardiovascular, and neuropsychologic status, and the presence of benign and malignant tumors. Patients with early-stage disease who were treated with radiation had scoliosis reported, along with other musculoskeletal abnormalities (32 versus 2), nearly seven times as often as did the members of the cohort population who did not undergo radiation (35 of 57 versus 5 of 53, respectively). The difference in cardiovascular problems recorded in survivors who did and did not receive Adriamycin (Adria Laboratories, Columbus, OH) (2.4 versus 1.1 per 100-person years at risk) had borderline statistical significance (P = 0.06). No excess in neuropsychologic events was reported for those given the neurotoxin vincristine. When considering patients with disease of all stages, all 5 second malignant tumors occurred in the 623 patients who underwent radiation (RT patients); benign tumors were also more frequent in RT patients than in those patients who did not undergo radiation (41 of 486 or 8% versus 4 of 194 or 2%). Continuing study of this unique body of patients is needed, especially for those given Adriamycin, because of the known long interval needed for latent cardiomyopathy to become clinically manifest in some patients.     

The effects of phorbol esters with different biological activities on protein kinase C

The sapintoxins are a series of naturally occurring fluorescent phorbol esters with a range of selective biological activities (e.g. pro-inflammatory but non-tumour promoting). Their ability to activate protein kinase C (PKC) in vitro has been studied. Both tumour promoting and non-promoting phorbol derivatives activate the enzyme in vitro at low concentrations. 12-deoxyphorbol-13-phenylacetate-20 acetate (DOPPA) acts as a partial agonist in the activation of protein kinase C. Structurally distinct phorbol esters may therefore preferentially activate different forms of protein kinase C. α-sapinine, a biologically inactive compound, binds to protein kinase C without stimulating the enzyme and prevents subsequent activation by phorbol esters such as 12-O-tetradecanoyl phorbol-13-acetate (TPA).     

Death of a classified worker probably caused by overexposure to gamma radiation.

This paper describes the case of an industrial radiographer who was seriously overexposed to gamma radiation. The exact circumstances of this exposure were not established but it was concluded that he was repeatedly irradiated probably to a total average whole body dose of at least 10 Gy over several years. Also, a much larger dose to a hand required its partial amputation. He developed myelodysplasia, which progressed to acute myeloid leukaemia from which he died. Karyotypic examination of the leukaemic blasts showed changes very similar to those associated with secondary leukaemia that may develop after radio or chemotherapy. The paper describes his medical case history, the investigation of his workplace, and the attempts to estimate his radiation dose by chromosomal analysis of blood lymphocytes and electron spin resonance of dental enamel and bone.     

Estrogen-induced transcortin increase and progesterone and cortisol interactions: implications from pregnancy studies

The concentrations of progesterone, cortisol, estradiol, and transcortin binding capacity (TBC) were measured in plasma samples of women during normal pregnancy. Between 10 weeks and 20 weeks gestation, the mean of TBC increased linearly, and the mean increase in TBC for a given estradiol increment was constant until the estradiol concentrations reached approximately 30 nmol per liter. The results were consistent with the increase in TBC having been induced by estradiol; however, there was an inherent upper limit of response. Progesterone and cortisol were each linearly related to TBC, but the ratios of progesterone:TBC and cortisol:TBC showed no systematic trend throughout the period studied, and there was no systematic relationship between TBC and the progesterone:cortisol ratio. There was, however, a linear relationship between TBC and the progesterone + cortisol sum, such that a unit increase in TBC was accompanied by an approximate unit increase in the total concentration of the two main transcortin binding steroids. Some cases of spontaneous abortion or habitual abortion might be due to aberrant metabolic influence on progesterone of binding protein; in the instances studied, no evidence was found for this.     

Effect of the method of breast feeding on breast engorgement, mastitis and infantile colic

This exploratory study compared the effect of two methods of breast feeding on breast engorgement, mastitis, infantile colic and duration of breast feeding. An opportunity sample of subjects was assigned either to the experimental group (prolonged emptying of one breast at each feed) (n = 150) or to the control group (both breasts equally drained at each feed) in = 152) and both groups were followed prospectively to 6 months after delivery. The experimental group had a lower incidence of breast engorgement in the first week (61.4% versus 74.3%; p < 0.02) and colic over the first 6 months (12% versus 23.4%; p < 0.02). There was no significant difference between the two groups in the incidence of mastitis over 6 months and the length of breast feeding (16.510.3 weeks versus 17.510 weeks experimental versus control group). The majority of mothers in the experimental group (63%) felt it necessary to offer the second breast at the end of a feed to satisfy their infant's hunger. The "perceived insufficient milk supply syndrome" was the main reason given for cessation of breast feeding in both groups. This study provides data to advise nursing mothers about these two methods of breast feeding. Breast engorgement, breast feeding methods, foremilk, hindmilk, infantile colic, mastitis
K Evans, Department of Nursing (ward 4C), Flinders Medical Centre, Bedford Park, South Australia 5042, Australia     

Automated quantification of thyrotropin by radial partition immunoassay

We describe a radial partition enzyme immunoassay in which fully automated quantification of human thyrotropin (hTSH) takes less than 11 min. This "sandwich"-type assay involves two monoclonal antibodies, both specific for the intact hTSH molecule. The solid phase consists of tabs of glass-fiber filter paper containing a pre-immobilized monoclonal anti-hTSH antibody complexed with a goat antibody specific for the Fc region of mouse IgG. The patient's sample is first applied to the central "reaction zone" of the tab, wherein hTSH binds to the immobilized antibody. Application of a buffered solution containing enzyme-labeled Fab' fragments of the second monoclonal anti-hTSH antibody initiates "sandwich" formation. A wash buffer containing a fluorogenic substrate elutes unbound conjugate to the tab periphery. The bound enzyme conjugate is quantified by measuring the rate of increase in fluorescence in the reaction zone of the tab, then converting the rate to clinical units by comparison with a stored calibration curve. The clinical utility and performance of the present assay compare favorably with those of other sensitive assays for hTSH.     

Use of animals in biomedical research. Historical role of the American Medical Association and the American physician

From the introduction of the "Gallinger-DC" bill in 1896 to the passage of the Laboratory Animal Welfare Act in 1966, organized medicine and the American physician have been active in promoting the humane and appropriate use of research animals and explaining to the public and legislators the importance of research using animals to medical progress. The role of organized medicine and science in events leading to passage of federal legislation is discussed. Past efforts of the American Medical Association and the American physician have been critical in numerous successful efforts at the local, state, and national level to prevent the passage of laws which restricted animal use for health research and impeded medical progress. This article demonstrates that current initiatives by physicians to preserve biomedical research are a reaffirmation of their traditional role.     

Mechanism of platelet effects of cardiotoxins from Naja nigricollis crawshawii (spitting cobra) snake venom

Four cardiotoxins isolated from Naja nigricollis crawshawii venom show inhibition of platelet aggregation when tested on whole blood aggregation in an electronic aggregometer. A similar inhibitory effect is observed by adding hemolyzed erythrocytes to whole blood before initiation of aggregation with collagen. Qualitatively, ADP-induced aggregation in whole blood appears to be different from collagen-induced aggregation in that the change in impedance is smaller than that induced by collagen. Thus, addition of ADP apparently "inhibits" collagen-induced aggregation as measured by the electronic aggregometer. Inclusion of apyrase in the aggregation cuvet stimulates the rate of aggregation initiated by collagen. The cardiotoxins lyse blood cells and release their cellular contents including ADP, AMP and other inhibitory substances, which reduce the impedance changes associated with collagen-induced aggregation. The cardiotoxins also lyse platelets coated onto the electrodes and reduce the impedance after aggregation is completed. Thus the lytic effects of these polypeptides cause an apparent inhibition of platelet aggregation in whole blood by both release of inhibitory components and removal of platelets from the electrodes. The lytic ability of these cardiotoxins can also explain the apparent "potentiation" and "aggregation" observed by previous workers using turbidometric aggregometers. Under these conditions, the cardiotoxins from N. nigricollis appear to both potentiate ADP-initiated aggregation and initiate aggregation themselves, but lysis is responsible, as shown by the release of cytoplasmic lactate dehydrogenase. Neurotoxin II from N. naja oxiana venom, although structurally homologous with cardiotoxins, does not lyse cells, nor did it show any effects on platelets.