Coordinated weather balloon solar radiation measurements during a solar eclipse.

Solar eclipses provide a rapidly changing solar radiation environment. These changes can be studied using simple photodiode sensors, if the radiation reaching the sensors is unaffected by cloud. Transporting the sensors aloft using standard meteorological instrument packages modified to carry extra sensors, provides one promising but hitherto unexploited possibility for making solar eclipse radiation measurements. For the 20 March 2015 solar eclipse, a coordinated campaign of balloon-carried solar radiation measurements was undertaken from Reading (51.44°N, 0.94°W), Lerwick (60.15°N, 1.13°W) and Reykjavik (64.13°N, 21.90°W), straddling the path of the eclipse. The balloons reached sufficient altitude at the eclipse time for eclipse-induced variations in solar radiation and solar limb darkening to be measured above cloud. Because the sensor platforms were free to swing, techniques have been evaluated to correct the measurements for their changing orientation. In the swing-averaged technique, the mean value across a set of swings was used to approximate the radiation falling on a horizontal surface; in the swing-maximum technique, the direct beam was estimated by assuming that the maximum solar radiation during a swing occurs when the photodiode sensing surface becomes normal to the direction of the solar beam. Both approaches, essentially independent, give values that agree with theoretical expectations for the eclipse-induced radiation changes.This article is part of the themed issue 'Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse'.

Genomancy: predicting tumour response to cancer therapy based on the oracle of genetics.

Cells are complex systems that regulate a multitude of biologic pathways involving a diverse array of molecules. Cancer can develop when these pathways become deregulated as a result of mutations in the genes coding for these proteins or of epigenetic changes that affect gene expression, or both1,2. The diversity and interconnectedness of these pathways and their molecular components implies that a variety of mutations may lead to tumorigenic cellular deregulation3-6. This variety, combined with the requirement to overcome multiple anticancer defence mechanisms7, contributes to the heterogeneous nature of cancer. Consequently, tumours with similar histology may vary in their underlying molecular circuitry8-10, with resultant differences in biologic behaviour, manifested in proliferation rate, invasiveness, metastatic potential, and unfortunately, response to cytotoxic therapy. Thus, cancer can be thought of as a family of related tumour subtypes, highlighting the need for individualized prediction both of disease progression and of treatment response, based on the molecular characteristics of the tumour.

Treatment type and symptom severity among oncology patients by self-report.

Oncology patients receiving chemotherapy (n=109) and radiation therapy RT (n=161) reported symptom concerns and severity on the 25-item therapy-related symptom checklist (TRSC). Secondary analysis of the self-reports of the two treatment groups was done using the Mann-Whitney U Test. Thirteen symptoms differed significantly between the two groups. RT patients reported significantly greater severity of five symptoms (p<0.05) during therapy. Chemotherapy patients reported significantly greater severity of eight different symptoms. The other 14 items showed a heterogeneous pattern of self-reported patient symptom concerns. The TRSC appears to be a clinically useful self-report checklist that captures the more important symptom concerns of both RT and chemotherapy patients. Earlier efforts to develop this checklist are reviewed briefly.

Immunological, physiological and pathological responses of rainbow trout (Oncorhynchus mykiss) to increasing dietary concentrations of soybean proteins.

High concentrations of dietary soya were shown to suppress salmonid growth rates and non-specific immune capacity. The immunosuppression became evident at dietary inclusion rates of 60-70% and was coincident with a reduction in weight gains and the appearance of demonstrable pathological changes in the distal intestine. Further increases in soya concentrations to 80-89% caused a progressive decline in specific growth rates and exacerbation of the intestinal pathology. There was no evidence of circulating antibody responses to dietary soybean proteins at any of the rates of inclusion. These observations confirm the findings of other authors that, at concentrations of up to 20-30% inclusion in diets, soybean proteins can provide a partial replacement for fish meal, but at higher concentrations detrimental effects become apparent, not only through reduced weight gains, but also through other physiological and immunological changes.

Nonpeptide oxytocin antagonists: potent, orally bioavailable analogs of L-371,257 containing a 1-R-(pyridyl)ethyl ether terminus.

Structure-activity studies on the oxytocin antagonist 1 (L-371,257) have identified a new series of high affinity, receptor-selective OT antagonists in which the N-acetyl-4-piperidinyl ether terminus in 1 has been replaced with a 1-(aryl)ethoxy group.

Outcomes of a nursing intervention for siblings of chronically ill children: a pilot study.

PURPOSE: To evaluate the outcomes of a structured, educational, and support group intervention (ISEE, Intervention for Siblings: Experience Enhancement) for siblings of children with chronic illness (cancer, cystic fibrosis, diabetes, and spina bifida), including a session with parents about sibling needs; and to describe sibling and parent perceptions of sibling experiences at home. DESIGN: One-group, pretest-posttest pilot study. PARTICIPANTS: A convenience sample of 22 siblings and parents. SETTING: A Midwestern university medical center. MAIN OUTCOME MEASURES: Knowledge of Illness Test, parent ratings on a global, single item, 10-point scale. RESULTS: Sibling test scores increased significantly after intervention, compared to baseline. Parents' average evaluation rating was 9 on a 10-point scale. Parents supported their positive ratings with verbatim descriptions. Sibling and parent perceptions of sibling experiences were congruent, suggesting the sources of potential adjustment problems in siblings, and were consistent with the literature. CONCLUSIONS: A randomized, clinical trial with a larger sample size is needed to evaluate the intervention further.

Mothers' intention, age, education and the duration and management of breastfeeding.

The authors examined the breastfeeding duration and management of two groups of mothers with different exposures to services of a Certified Lactation Consultant (CLC). One group of mothers, at hospital H1 (n = 46), had access to a CLC, while mothers at hospital H2 (n = 115) did not. Results showed that: (a) mothers at H1 had significantly (t = 2.33, p < .02) longer durations of breastfeeding (M = 3.1 months, SD = 1.2) than peers at H2 (M = 2.4 months, SD = 1.2); (b) a significantly greater proportion of mothers at H1 attained their intended duration of breastfeeding compared to mothers at H2 (Mann-Whitney U, one-tailed test, Z = 1.94, p < .05); and (c) in a stepwise multiple regression analysis, intended length of breastfeeding accounted for 18% of the variance in duration of breastfeeding, mothers' age 9%, and mothers' education 3%. The results support the theory of reasoned action and the theory of patient education.

PIP: The beneficial impact of certified lactation consultants on the duration of breast feeding was demonstrated in a hospital-based study conducted in the southwestern US. These consultants help new mothers to achieve their desired duration of breast feeding and to overcome technical problems through home visits and telephone contact. Compared were the breast feeding histories of 46 new mothers who delivered at a hospital that employed the services of a lactation consultant and the experiences of 115 new mothers who delivered at a hospital in the same community that lacked such a resource. In both hospitals, the majority of mothers were White and married. As hypothesized, the mean duration of breast feeding was significantly longer among mothers provided with the services of a lactation consultant (3.1 months) than among those who did not receive this service (2.4 months). In addition, 71% of the former mothers compared to only 54% of the latter mothers achieved or exceeded their originally intended breast feeding duration.

A comparison of two methods of assessing cancer therapy-related symptoms.

Patients undergoing outpatient cancer treatment experience a multitude of therapy-related symptoms. Complete assessment of these symptoms is essential for proper interventions to be provided and to enhance the quality of life of the patient. The primary purposes of the study were to compare the number of symptoms identified by a self-report instrument with those documented in the patient's medical record, and to examine the relationship between the number of self-reported symptoms and quality of life. Ninety-one oncology patients from three outpatient clinics participated in the study. The Oncology Treatment Toxicity Assessment Tool (OTTAT) and the Quality of Life Index (QLI) are self-report instruments, each with 37 items and 18 items, respectively. The mean number of symptoms reported on the OTTAT (mean = 11; range 0-37; SD 8) was significantly higher than that documented in the medical record (mean = 1.5 range 0-9; SD 1.6), (t = 8.7, p = 0.001). Higher scores on the OTTAT were significantly related to lower scores on the QLI (r = -0.67, p = 0.0001).

Vancomycin-induced release of histamine from rat peritoneal mast cells and a rat basophil cell line (RBL-1).

Rapid intravenous administration of the glycopeptide antibiotic, vancomycin, may cause a hypotensive reaction which can usually be prevented by infusing vancomycin in dilute solutions. The release of histamine from circulating cells such as basophils and tissue mast cells has been implicated in hypotensive reactions since the effects can be prevented by antihistamine pretreatment. The direct effects of vancomycin on histamine release were therefore investigated in rat peritoneal mast cells and rat leukemic basophils (RBL-1 cells). Suspension cultures of mast cells or RBL-1 cells were exposed to vancomycin for 30-60 minutes at concentrations comparable to those infused clinically (2.28 or 4.56 mg/ml). Vancomycin induced a time- and dose-dependent release of histamine into the culture media from both cell types. The reference degranulating agent, Compound 48/80 (CP 48/80), was also shown to induce histamine release from mast cells and RBL-1 cells. Mast cells were significantly more sensitive to vancomycin and CP 48/80 than RBL-1 cells and, unlike RBL-1 cells, were responsive to the inhibitory effects of cromolyn sodium on histamine release. Cromolyn sodium did not inhibit vancomycin-induced histamine release in RBL-1 or mast cells. Morphologically, mast cells exposed to either vancomycin or CP 48/80 exhibited dose-related degranulation. On the other hand, treatment-related degranulation effects of either vancomycin or CP 48/80 on RBL-1 cells could not be reliably distinguished from controls by qualitative evaluation. Based upon these findings it is concluded that mast cells may represent a more useful model to evaluate the potential of investigational agents to release histamine and to study mechanisms of histamine release than RBL-1 cells.

Relationship between in vitro relaxation of the costo-uterine smooth muscle and mesovarial leiomyoma formation in vivo by beta-receptor agonists.

The three beta-agonists, salbutamol, ritodrine, and terbutaline have been shown to possess differing potentials to induce leiomyomas in rat costo-uterine muscle following chronic exposure (salbutamol greater than terbutaline greater than ritodrine). It has been suggested that the potential to induce leiomyomas is related to the relaxant properties of these agonists in the costo-uterine muscle. In order to test this hypothesis, the potencies of salbutamol, terbutaline, and ritodrine were compared to isoproterenol and norepinephrine in vitro in the rat costo-uterine smooth muscle, a beta 2-adrenergic receptor rich tissue. All compounds produced relaxation of potassium chloride (KCl) contracted costo-uterine smooth muscle. Significant differences in potency were observed, with isoproterenol being the most potent, followed in rank order by salbutamol, terbutaline and ritodrine. The relative potency of the non-selective beta-blocker propranolol in inhibiting the agonist mediated relaxant activity was similar for all agonists examined, indicative of interactions at the same receptor site (Tallarida and Jacob 1979). When tested for beta-agonist activity in the guinea pig atria, salbutamol and ritodrine were less potent in these tissues compared to the costo-uterine muscle. In summary, the in vitro pharmacological potency of salbutamol, terbutaline and ritodrine correlated with the potential to induce leiomyoma formation in rat costo-uterine muscle following chronic exposure to the respective beta-agonists. These results indicate that the isolated rat costo-uterine muscle is a sensitive model for comparing the potency of beta-agonists, and may assist in establishing the risk of costo-uterine leiomyoma formation in chronic rat studies relative to agents such as salbutamol.

The role of pharmacological profiling in safety assessment.

The profiling of new drug candidates for general pharmacological properties requires a systematic examination of the functional effects of agents in a variety of in vitro and in vivo assays. Both the behavioral and physiological consequences of drug treatment are monitored in models of central nervous system, cardiovascular, autonomic, gastrointestinal, and renal functions. Broad functional profiling provides valuable information to the preclinical pharmacologist with respect to the selectivity of new agents and may serve to identify new and useful therapeutic indications of investigational drugs. At the same time, knowledge of the effects on these physiological systems can also play an important role in safety assessment. Pharmacological activity of a new agent that is both unintended and undesirable can be referred to as "pharmacological toxicity." In general, the spectrum of toxicities disclosed in pharmacological profiling includes a variety of acute functional or physiological effects which are not life-threatening and are readily reversible. On rare occasions, unanticipated and life-threatening pharmacological effects (e.g., convulsions, arrhythmias) are detected which can seriously detract from the usefulness of a new agent and may therefore deter the drug development process. It should also be noted that repeated exposure to acute pharmacological effects may lead to less obvious chronic findings, such as target organ effects or tumor formation in animals. The interpretation of pharmacological toxicity with respect to the safety profile of a new drug candidate is dependent not only upon the types of reactions observed and the doses at which they occur but also upon the nature of the effects elicited as to whether they represent expected extensions of the primary mechanism of action of a compound or constitute reactions unrelated to the primary pharmacological activity. The ultimate impact of pharmacological toxicity, as with all adverse findings in preclinical assessment, is dependent upon the projected therapeutic margin of safety as well as the risk-to-benefit ratio for new drug entities. In addition to supplementing the existing armamentarium of preclinical safety studies, pharmacological profiling can also play an important role in (1) the selection of new drug candidates with reduced toxic potential, (2) the design and conduct of preclinical toxicology studies, (3) the investigation of preclinical and clinical safety issues, and (4) the identification of potential functional effects to be monitored most closely in clinical trials of new drug entities.

Transepithelial acidification by cultures of rabbit proximal tubules grown on filters.

Transepithelial acidification in the proximal tubule occurs by the simultaneous actions of the Na(+)-H+ exchanger in the brush border and the basolateral Na(+)-HCO3- cotransporter. The presence of these systems has been demonstrated for cultured cells; however, their contributions to the transepithelial movement of acid equivalents has not been confirmed in monolayers. To examine transepithelial acidification by intact cells, tubules were grown on membrane filters. Confluent cultures developed a transepithelial pH gradient within 6 h by decreasing the pH of medium in the apical chamber (6.66 +/- 0.03) while raising the basolateral pH to 7.40 +/- 0.02. Cells maintained on plastic did not acidify the medium during this time. Amiloride (10-100 microM) inhibited development of the gradient only when placed in the top chamber. 4-Acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS; 10-100 microM), which inhibits basolateral Na(+)-HCO3- cotransport, decreased the gradient only when added to the bottom. These results demonstrate that cultured proximal tubule cells can develop a transepithelial pH gradient and that the polarized distribution of the transport systems is maintained in vitro.

The application of renal cells in culture in studying drug-induced nephrotoxicity.

Kidney cells in culture represent one of many in vitro approaches for studying drug-induced nephrotoxicity. Potential advantages of cell culture systems compared to more traditional in vitro models include a) the ability to examine direct effects at the cellular level, b) extended viability, c) ability for long-term storage, and d) capabilities for automation. Primary cultures of kidney tubules as well as cell lines of kidney origin are currently under evaluation as model systems for the assessment of nephrotoxicity. The application of two renal cell systems, rabbit primary proximal tubule cultures and the pig kidney cell line, LLC-PK1, in studying mechanisms of drug-induced nephrotoxicity is described in this communication. Potentially valuable insights into the renal pathogenesis associated with the antitumor agent, cis-diamminedichloroplatinum II, and the aminoglycoside antibiotic, gentamicin, have been obtained utilizing these renal cell models. Challenges in renal cell culture involve the characterization and maintenance of differentiated properties and the development of technologies to a) study bidirectional transport-toxicity of drugs, and b) provide a dynamic vs. static fluid environment as in vivo. Despite these unique challenges as well as the universal challenges involved in extrapolating any in vitro data to the in vivo situation, recent studies indicate that renal cells in culture are useful in the elucidation of mechanisms of drug-induced renal injury.

Effects of cis-diamminedichloroplatinum(II) on rabbit kidney in vivo and on rabbit renal proximal tubule cells in culture.

The nephrotoxic potential of cis-diamminedichloroplatinum(II) (CDDP) in rabbits, as well as its effect on cell viability, cellular synthetic activity, and specific enzyme activities in rabbit renal proximal tubule cells, was investigated. Male New Zealand White rabbits were given a single i.v. dose of either 2.5 or 5.0 mg/kg CDDP via the ear vein and sacrificed 5 days later. No drug-induced changes were observed in the kidneys of rabbits given 2.5 mg/kg CDDP. However, histopathological examination of kidneys from rabbits administered 5.0 mg/kg CDDP revealed marked tubular degeneration and necrosis, with the majority of lesions being situated in the outer zone of the cortex. This is in contrast to the effect of CDDP in the kidney of the rat where the necrosis is reported to be predominantly localized to the pars recta of the proximal tubule in the outer stripe of the medulla. The results from the in vitro experiments indicated that the viability of cells after a 6-h exposure to CDDP at concentrations up to 100 microM was greater than 95%. However, a dose-dependent decrease in cell viability was obtained after 24 h exposure with a TD50 (50% viability) of approximately 90 microM. In addition, the results after 24 h exposure to CDDP also indicated that Na+, K+-ATPase, a basolateral membrane marker enzyme, and alkaline phosphatase, a brush-border marker enzyme, were inhibited by 35-40% and 20%, respectively. No effect on succinic dehydrogenase, a mitochondrial marker enzyme, was obtained. Inhibition of all three marker enzymes was minimal at 6 h posttreatment. On the other hand, inhibition of DNA, RNA, and protein syntheses was evident as early as 6 h posttreatment with DNA (48-77%) and RNA (36-77%) syntheses being inhibited to a greater extent than protein synthesis (14-33%). These results demonstrate that inhibition of renal synthetic activity by CDDP, rather than its effect on enzyme activity, precedes the onset of cell lethality and may therefore be an important event in the initiation of CDDP-induced nephrotoxicity.

Effects of preparation for mastectomy/hysterectomy on women's post-operative self-care behaviors.

The research problem was: what are the effects of preparation for mastectomy/hysterectomy on women's self-care behaviors during the immediate post-operative period, and 1 month after surgery? Study subjects were 60 women, 30 mastectomy and 30 hysterectomy, equally divided into an experimental and control group. The independent variable, structured teaching, was administered by a nurse clinician before and after surgery. The dependent variable, self-care, during the immediate post-operative period, was defined as the performance of three ambulation tasks on day 1. Five additional exercises were rated for the mastectomy group on day 1 and four on day 2. Task performance was rated on three criteria: time interval, amount of prompting and amount of assistance required for the first complete performance (as demonstrated and practiced pre-operatively) of each exercise. During the clinic phase, 1 month post-surgery, self-care was the score obtained on a Self-Care Rating Scale, obtained by patient report and based on the discharge planning content. Findings showed that for the in-hospital phase, patients in the group given pre-operative instructions performed at a significantly higher level. They required neither prompting nor assistance in the initiation and completion of ambulation tasks compared to the uninstructed group. Most patients in the uninstructed group did not initiate nor complete the tasks despite prompting and physical assistance from the nurse. For the clinic phase, both the instructed post-mastectomy and post-hysterectomy groups performed self-care activities at home significantly better than and more frequently than the uninstructed groups.

Clinical significance of erythropoietin levels in renal carcinoma.

The bioassay using the polythemic mice demonstrated persistent erythropoietin (Ep) activity in 24 renal carcinoma patients. Eight patients without clinical evidence of renal carcinoma had Ep levels that were slightly higher than those of controls, suggesting the possibility of occult disease. Increased levels of Ep were noted in 5 patients with other genitourinary carcinomas. This selective study reaffirms the value of Ep as a biologic marker in some renal cell cancers, and occasionally in other genitourinary tumors.

Inhibition of renal membrane binding and nephrotoxicity of aminoglycosides.

The initial event in the renal tubular reabsorption of nephrotoxic aminoglycosides involves binding to brush border membranes. This primary event was measured in renal brush border membrane vesicles prepared from rat renal cortex utilizing [3H]gentamicin. In order to gain structure-activity information regarding this interaction the effect of substances having chemical similarities to aminoglycosides (sugars, polyamines and amino acids) on gentamicin binding to brush border membranes was determined. Polyamino acids were found to possess the greatest inhibitory potency. In addition to polymers of cationic amino acids (lysine, ornithine, arginine and histidine), polymers of neutral (asparagine) and acidic (aspartic and glutamic acid) amino acids also exhibited inhibition of the membrane binding of gentamicin. Inasmuch as inhibition of renal membrane binding has the potential to decrease aminoglycoside nephrotoxicity, several polyamino acids that inhibited membrane binding were tested in vivo for potential protective activity vs. gentamicin- and amikacin-induced nephrotoxicity. Polyasparagine90 and polyaspartic acid100 inhibited gentamicin and amikacin nephrotoxicity completely when coadministered to rats with the aminoglycosides. Polylysine20 provided complete and partial inhibition of gentamicin and amikacin nephrotoxicity, respectively. Whereas in vivo distribution studies revealed that cortical levels of [3H]amikacin were elevated slightly by the coadministration of polyaspartic acid, brush border and basolateral membranes contained significantly lower levels of the aminoglycoside (46 and 41% inhibition, respectively). These results question the role of charge per se in the binding of aminoglycosides to renal membranes and further confirm the importance of membrane binding in the pathogenesis of aminoglycoside nephrotoxicity.

Comparative nephrotoxicity of carboplatin and cisplatin in combination with tobramycin.

The nephrotoxic potentials of cisplatin and carboplatin, alone and in combination with the aminoglycoside antibiotic tobramycin, were compared in male rats. Sixty (60) male Sprague-Dawley rats were divided into six groups of ten rats each and received the following treatments: Group I, saline; group II, cisplatin (5 mg/kg); group III, cisplatin (5 mg/kg) + tobramycin (50 mg/kg); group IV, carboplatin alone (50 mg/kg); group V, carboplatin (50 mg/kg) + tobramycin (50 mg/kg); and group VI, tobramycin alone (50 mg/kg). Carboplatin and cisplatin were each administered as a single i.v. injection on day 1. Tobramycin was administered i.-m. once daily on days 1-5. All rats were euthanatized on day 6. Smaller body weight gains occurred in groups II-V than in saline controls. Serum urea nitrogen (BUN) levels recorded on day 6 were elevated in group III. BUN values of all other groups were normal. Histopathologic examination of kidneys revealed acute tubular injury in rats treated with cisplatin, whether alone or in combination with tobramycin, and in carboplatin/tobramycin-treated rats. Carboplatin and tobramycin, when administered separately, were not nephrotoxic. The combination of cisplatin and tobramycin proved to be the most nephrotoxic treatment.