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Methylene Chloride: A Two-Year Inhalation Toxicity and Oncogenicity Study in Rats and Hamsters. BUREK, J. D., NITSCHKE, K. D., BELL, T. J., WACKERLE, D. L., CHILDS, R. C., BEYER, J. E., DITTENBER, D. A., RAMPY, L. W., AND MCKENNA, M. J. (1984). . 4, 30–47. A long-term study was conducted to determine the possible chronic toxicity and oncogenicity of methylene chloride. Rats and hamsters were exposed by inhalation to 0, 500, 1500, or 3500 ppm of methylene chloride for 6 hr per day, 5 days a week, for 2 years. No exposure-related cytogenetic effects were present in male or female rats exposed to 500, 1500, or 3500 ppm. Females rats exposed to 3500 ppm had an increased mortality rate while female hamsters exposed to 1500 or 3500 ppm had decreased mortality rates. Carboxyhemoglobin values were elevated in rats and hamsters exposed to 500, 1500, or 3500 ppm with the percentage increase in hamsters greater than in rats. Minimal histopathologic effects were present in the livers of rats exposed to 500, 1500, or 3500 ppm. Decreased amyloidosis was observed in the liver and other organs in hamsters exposed to 500, 1500, or 3500 ppm. While the number of female rats with a benign tumor was not increased, the total number of benign mammary tumors was increased in female rats in an exposure-related manner. This effect was also evident in male rats in the 1500- and 3500-ppm exposure groups. Finally, male rats exposed to 1500 or 3500 ppm had an increased number of sarcomas in the ventral neck region located in or around the salivary glands. Therefore, in this 2-year study, some effects were observed in male and female rats exposed to 500, 1500, or 3500 ppm of methylene chloride. In contrast, hamsters exposed to the same exposure concentrations had less extensive spontaneous geriatric changes, decreased mortality (females), and lacked evidence of definite target organ toxicity. [ABSTRACT FROM PUBLISHER]

The reproductive strategy of most fishes is to produce a large number of tiny eggs, leading to a huge difference between egg size and asymptotic body size. The viability of this strategy is examined by calculating the life-time reproductive success R(0) as a function of the asymptotic body size. A simple criterion for the optimality of producing small eggs is found, depending on the rate of predation relative to the specific rate of consumption. Secondly it is shown that the success of the reproductive strategy is increasing with asymptotic body size. Finally the existence of both upper and lower limits on the allowed asymptotic sizes is demonstrated. A metabolic upper limit to asymptotic body size for all higher animals is derived.

The effectiveness of analgesia during sickle cell crisis was examined in this descriptive, exploratory study. Pain scores (using the African-American Oucher and the Adolescent Pediatric Pain Tool) and analgesics administered were examined during a 2-hour observation/interview in the hospital while children/adolescents with sickle cell disease (SCD) experienced a vaso-occlusive episode (VOE). A convenience sample of twenty-one 6- to 16-year olds with SCD was included. Evidence indicated that 15 of the 21 children in the sample were in moderate to severe pain during their interviews, indicating that the analgesics did not effectively control their pain. Most participants (17) had received nalbuphine as the primary analgesic by intravenous infusion drip and/or patient-controlled analgesia pump. Many reasons were identified for the inadequate analgesia. The results suggested that the pain of SCD is very complex, requiring continuous adjustment of comfort measures, especially analgesics. More research is needed to examine pain control in children with SCD.

Objective: To examine the patterns of children's and caregivers' descriptions of pain and the comfort measures used to relieve the pain of sickle cell disease (SCD) at home and in the hospital., Design: Qualitative and quantitative techniques were used to obtain data. Participants were seen twice, first with and then without a vaso-occlusive episode. Multiple simultaneous methodological triangulation was used to integrate the findings from ethnographic interviews and observations as well as limited quantitative findings about pain and comfort measures used., Setting: A Midwestern children's hospital with a regional SCD service., Participants: Twenty-one African American children and adolescents with SCD, aged 6 to 15 years, and 21 family caregivers., Results: An 8-phase chronology of pain and comfort was revealed from the data about pain and comfort in children with SCD. Although this chronology was an unexpected finding, it was consistent with the original aim of the investigation. Phase 1 (baseline) represented the usual state of the child's condition, which for most was free of pain. Phase 2 or the "pre-pain" state involved no vasoocclusive pain but the child began to show prodromal signs and symptoms of painful episodes, such as yellowing of the eyes or fatigue. Phases 2 through 7 involved increasing then decreasing levels of pain, including the pain start point (phase 3), pain acceleration (phase 4), peak pain experience (phase 5), pain decrease start point (phase 6), and steady pain decline (phase 7). A trip to the emergency department usually occurred during phase 5. In phase 8 (pain resolution), the pain had decreased to a manageable level so that the child could be discharged from the hospital. As pain increased and decreased, so did the number and variety of comfort measures., Conclusions: A chronology of the pain and comfort experiences for children and adolescents during a vasoocclusive event of SCD emerged from the descriptive data of this study. Findings need to be examined further in larger, quantitative, longitudinal studies that examine more closely the duration, intensity, and character of pain at different times during vaso-occlusive episodes as well as the comfort measures used during specific phases of the pain event.

Issues and Purpose: Pain is the most frequent and important problem for children with sickle cell disease (SCD), but it has been undertreated and understudied. A multidisciplinary group of healthcare providers, academics, and people with SCD and their families met to (1) examine the pain of vaso-occlusive events (VOE) in children and adults with SCD and (2) reach consensus about necessary improvements in care., Conclusions: Accurate assessment of pain is at the crux of effective care for children with VOE. This requires a trusting interactive relationship among patient, family, and healthcare team. Comprehensive pain assessment is a lifelong process in need of continued updating., Practice Implications: Children with SCD seek treatment from nurses in many settings. Traditional care has been frustrating to both families and care providers. Children and adolescents with SCD pain would benefit from nursing care that considers patients' perspectives about pain and comfort as key determinants for treatment. A unified approach to pain assessment may be a significant factor in improving pain control.

This study examined the construct validity of the African-American and Hispanic versions of the Oucher Scale as measures of pain in 104 children ages 3 to 12 years old. Scores on the Oucher Scale, Analogue Chromatic Continuous Scale, and Child Medical Fear Scale were obtained after being administered concurrently on one occasion, either before or after surgery. Additionally, Oucher scores were obtained before and after analgesic administration. Significant correlations were found between the two pain intensity measures, while weak, nonsignificant relationships were revealed between the pain and fear measures. Preanalgesic scores were significantly higher than postanalgesic scores. These findings support the construct validity of the two new ethnic versions of the Oucher.

This is the first article written by this group of authors/researchers who are collaborating on the development of the Oucher, an assessment tool to assist 3- to 12-year-olds describe the intensity of pain. The background and conceptual framework for its development, the research supporting the validation of the original Oucher, the research to create new ethnic versions, and the basic instructions for clinical use are described. In addition, several issues regarding the continued development and use of the Oucher are identified, including those relative to poster size and the gender and ethnicity of the photographed child. This article illustrates the precision and care needed to create clinically useful tools for obtaining information directly from young children.

A randomized, double-blind, prospective study was performed to determine the effects of perioperative administration of morphine or methadone on postoperative analgesic requirements and pain scores in 35 children aged 3 to 7 years undergoing major surgery. After a standardized induction of anesthesia, methadone or morphine, 0.2 mg/kg, was blindly administered, and supplemental doses were titrated to achieve comfort in the recovery room. Pain was assessed during the next 36 hours with a combination of validated behavioral and self-report measures. Patients in the methadone group required fewer supplemental opioid analgesic drugs during the next 36 hours, and reported lower pain scores. No patient had prolonged emergence from anesthesia, and no patient required naloxone or postoperative ventilatory assistance. No major adverse events occurred. We conclude that perioperative intravenous administration of methadone is an effective, inexpensive, and technologically simple means for providing prolonged analgesia for children after surgery.

This study examined concurrent self-reports of pain intensity and behavioral responses in 25 children aged 3-7 yr. Behavioral (Children's Hospital of Eastern Ontario Pain Scale, CHEOPS) and self-report (the Oucher and Analogue Chromatic Continuous Scale) measures of pain were obtained following major surgery. The two self-report measures were strongly and significantly correlated, and the pattern of scores over the 36-hr observation period was as expected. There was little relationship between the scores for the self-report and the behavioral measures. Many children who reported severe pain manifested few of the behavioral indicators of distress used in the CHEOPS. This behavioral response pattern may occur commonly in children experiencing pain after surgery and may limit the applicability of current behavioral scales as sole measures of pain intensity in younger children.

Using a cross-sectional mail survey and random sampling, the interpersonal aspect of the relationship among nursing faculty colleagues was examined. A sample of 222 full-time, female educators in baccalaureate schools of nursing in Texas returned their anonymous questionnaires, providing information about themselves, their work, and the communication among their faculty colleagues. Findings revealed that actual interpersonal interactions among colleagues were less supportive than was desirable and that nurse educators were dissatisfied with collegial communication. At the same time, having supportive colleagues was found to be a highly important part of their jobs. Degree of involvement in curriculum revision and perceptions of faculty effectiveness in achieving goals were found to explain the most variance in the supportiveness of actual collegial interactions. Perceptions of effectiveness and years of experience in nursing education were found to explain the most variance in satisfaction with collegial communication.

Increased interest in the topic of pain has resulted in pharmacologic advances that provide new possibilities for pain relief in children. It has also resulted in new nonpharmacologic therapies that are now being used more frequently with children. It is hoped that these advances will continue so that health care providers will have a larger repertoire of pain control methods effective with children, and so that the traumatic aspects of hospitalization and health care can be reduced greatly. The pain experienced by children has heretofore been on the backroads of scientific and scholarly development. As a result, we actually know very little about pediatric pain, its measurement, and its treatment. The literature and research cited previously are strikingly limited for providing a base of knowledge to guide clinical practice. We avoided a "cookbook" approach to the discussion on pain control, because there are many of those available. Instead, we presented a summary of the research that is currently available in the attempt to help nurses better recognize the limitations in what we know with certainty about this important topic. We hope that this knowledge will spur readers to examine their own beliefs and knowledge, question former assumptions about pediatric pain, and promote a more inquiring approach to assessment and management of children's pain. Pain is a multidisciplinary problem. Although health care providers from the various disciplines each approach the pain problem from different angles, each approach has its place in the overall picture of solving the problems of pediatric pain control. Nurses have been and will continue to be a vital part of clinical and scientific advancements to move pediatric pain out of the realm of mystery and into the realm of the known.

Groups of 10 male New Zealand white rabbits were exposed by inhalation to 0, 0.1, 1.0 or 10 ppm of 1,2-dibromo-3-chloropropane (DBCP) vapor for 6 hours/day, 5 days/week for 14 weeks, except that the 10 ppm group was exposed for only 8 weeks due to mortality. The semen of rabbits was evaluated on a weekly basis during the exposure period and at periodic intervals during a recovery period (32 weeks for all groups except the 10 ppm groups which was for 38 weeks). In order to assess the fertility of the exposed rabbits, each male was allowed to mate with an unexposed female at the 14th and 41st week of the study. Exposure of rabbits to 1 and 10 ppm of DBCP by inhalation produced adverse reproductive effects as well as decreases in sperm count, motility and viability. Rabbits treated at 1 and 10 ppm had decreased sperm counts between the 8th and 14th weeks of the study. All of the 10 ppm rabbits were infertile when mated during the 14th week. The effects of DBCP on spermatogenesis were shown to be essentially reversible in rabbits exposed to 1 ppm; however, at 10 ppm, recovery was not complete under the conditions of the test. Rabbits exposed to 10 ppm had severe testicular alterations as early as 4 weeks into the study and these progressed to severe testicular atrophy by 8 weeks. Those exposed to 1 ppm for 14 weeks developed moderate testicular atrophy (approximately 50% reduction in size). Following the recovery period, the rabbits in the 10 ppm group had evidence of partial reversibility of the testicular atrophy. Electron microscopic evaluation of testicular tissue confirmed findings by light microscopy effects and also indicated increased numbers of abnormal sperm within the seminiferous tubules of rabbits at both the 10 and 1 ppm exposure levels. Those exposed to 0.1 ppm had an equivocal increase in abnormal sperm after the 14-week exposure period but not after the recovery period. Based on these results 0.1 ppm level of DBCP is considered as a no effect level for reproductive parameters.

This article focuses on the methods of pain measurement and assessment in children. The concepts of reliability and validity and the available types of physiologic, self-report, and behavioral measures are addressed. Methods of pain assessment in infants and toddlers, preschoolers, school-aged children, and adolescents are detailed. Finally, some practical suggestions for pediatric pain assessment are provided.

The chronic toxicity and oncogenic potential of ingested vinylidene chloride (VDC) was evaluated in a 2-year study on Sprague-Dawley rats and the subchronic toxicity was evaluated in beagle dogs in a 97-day study. The vinylidene chloride was incorporated in the drinking water of the rats at nominal concentrations of 50, 100 or 200 ppm. The time weighted average mg/kg body weight/day dosages of vinylidene chloride administered to the male and female rats over the 2-year period at the various mean analyzed concentrations were 7, 10 or 20 for the males and 9, 14 or 30 for the females. Dogs were administered vinylidene chloride in peanut oil incorporated in a gelatin capsule at concentrations which provided 6.25, 12.5 or 25 mg vinylidene chloride/kg body weight/day. There were no significant differences between the groups of rats or dogs ingesting vinylidene chloride and their corresponding control groups in the following parameters: appearance and demeanor, mortality, body weight, food consumption, hematology, urinalysis, clinical chemistry determinations, organ weights and organ to body weight ratios. There were no significant differences in water consumption of the groups of rats ingesting vinylidene chloride and the controls. The sole treatment-related observation in the rats, evident only upon microscopic examination, was in the liver. The observation was characterized by a minimal amount of hepatocellular swelling with midzonal fatty change which occurred in the females at all dose levels and in the males only at the 200 ppm level. No exposure-related neoplastic changes occurred in the rats in any of the test groups. No exposure-related gross or histopathological changes were present in the tissues taken from the dogs at the termination of the 97-day study.

Groups of male and female Fischer 344 rats were administered acrylamide in their drinking water at 0, 0.05, 0.2, 1, 5, or 20 mg/kg/day for up to 93 days. Following the administration of acrylamide in the drinking water, male rats from each dose level were held for up to 144 days of recovery. The 20 mg/kg/day groups had definite treatment-related effects after 92 (males) and 93 (females) days. They were dragging the rear limbs, body weights were decreased, serum cholinesterase activity was decreased in top dose females, and packed cell volume, red blood cell, and hemoglobin values were slightly decreased in males and females. In the 20 mg/kg/day groups, the primary target tissue was the peripheral nerve with lesions consisting of severe degeneration characterized by demyelinization and axonal loss. Slight spinal cord degeneration was observed. Other effects included atrophy of skeletal muscle, testicular atrophy, and distended urinary bladders; these were probably secondary to the nerve degeneration. After 144 days of recovery, the lesions had partially or completely reversed. Parameters affected at the 5 mg/kg/day dose level after 92 (males) and 93 (females) days consisted of peripheral nerve degeneration which were of a lesser degree of severity than those seen in the 20 mg/kg/day groups and appeared to have completely reversed after 111 days of recovery. In rats given 1 mg/kg/day, a minimal treatment-related effect was observed in males after 92 days, and this was limited to very slight nerve degeneration using electron microscopy (females were not examined by electron microscopy). This observed effect appeared to have reversed after 25 days of recovery. No treatment-related effects were seen in any of the parameters monitored in the rats given 0.05 or 0.2 mg/kg/day of acrylamide.

This paper focuses on some of the major issues surrounding the measurement of children's pain, particularly as they relate to problems of definition, level of measurement, dimensionality, reliability, and validity. The authors briefly describe some of the tools used with children and point out some of the problems that have resulted from the lack of well-tested, thoroughly validated instruments for children. As a common experience of hospitalized children, pediatric pain is creating concern within the health care community. The authors recommend that more attention be paid to the measurement issues surrounding this clinical phenomenon.

This paper focuses on the knowledge base about the assessment and management of postoperative pain in children. The first section deals with the nature and characteristics of postoperative pain. A description of current pain management practices with children, focusing on analgesic administration, is derived from available research literature. These reports suggest that postoperative pediatric pain relief may be inadequate. Recent advances in pain assessment and measurement in all age groups, particularly with verbal children and the new self-report measures, are discussed. The latest developments in pharmacological and nonpharmacological techniques for the relief of children's postoperative pain are also described. Finally, the paper concludes with a few suggestions for pediatricians relative to their role in assisting in the search for better assessment and management techniques in the care of postoperative children.