Intramedullary megakaryocytes internalize released platelet factor 4 and store it in alpha granules.

BACKGROUND: Megakaryocytes express and store platelet factor 4 (PF4) in alpha granules. In vivo, PF4 is a clinically relevant, negative regulator of megakaryopoiesis and hematopoietic stem cell replication. These findings would suggest a regulated source of free intramedullary PF4. OBJECTIVES: Define the source of free intramedullary PF4 and its intramedullary life cycle. METHODS: We interrogated both murine and human bone marrow-derived cells during megakaryopoiesis in vitro by using confocal microscopy and enzyme-linked immunosorbent assay. With immunohistochemistry, we examined in vivo free PF4 in murine bone marrow before and after radiation injury and in the setting of megakaryocytopenia and thrombocytopenia. RESULTS: Exogenously added human PF4 is internalized by murine megakaryocytes. Human megakaryocytes similarly take up murine PF4 but not the related chemokine, platelet basic protein. Confocal microscopy shows that internalized PF4 colocalizes with endogenous PF4 in alpha granules and is available for release on thrombin stimulation. Immunohistochemistry shows free PF4 in the marrow, but not another alphagranule protein, von Willebrand factor. Free PF4 increases with radiation injury and decreases with megakaryocytopenia. Consistent with the known role of low-density lipoprotein receptor-related protein 1 in the negative paracrine effect of PF4 on megakaryopoiesis, PF4 internalization is at least partially low-density lipoprotein receptor-related protein 1 dependent. CONCLUSIONS: PF4 has a complex intramedullary life cycle with important implications in megakaryopoiesis and hematopoietic stem cell replication not seen with other tested alpha granule proteins.

Pmel17 initiates premelanosome morphogenesis within multivesicular bodies.

Melanosomes are tissue-specific organelles within which melanin is synthesized and stored. The melanocyte-specific glycoprotein Pmel17 is enriched in the lumen of premelanosomes, where it associates with characteristic striations of unknown composition upon which melanin is deposited. However, Pmel17 is synthesized as an integral membrane protein. To clarify its physical linkage to premelanosomes, we analyzed the posttranslational processing of human Pmel17 in pigmented and transfected nonpigmented cells. We show that Pmel17 is cleaved in a post-Golgi compartment into two disulfide-linked subunits: a large lumenal subunit, M alpha, and an integral membrane subunit, M beta. The two subunits remain associated intracellularly, indicating that detectable M alpha remains membrane bound. We have previously shown that Pmel17 accumulates on intralumenal membrane vesicles and striations of premelanosomes in pigmented cells. In transfected nonpigmented cells Pmel17 associates with the intralumenal membrane vesicles of multivesicular bodies; cells overexpressing Pmel17 also display structures resembling premelanosomal striations within these compartments. These results suggest that Pmel17 is sufficient to drive the formation of striations from within multivesicular bodies and is thus directly involved in the biogenesis of premelanosomes.

Children of the Philippines: attitudes toward visible physical impairment.

OBJECTIVE: This pilot study was designed to evaluate children's attitudes and understanding of physical disabilities with special reference to those with craniofacial anomalies in the Philippines. Children with and without craniofacial anomalies were studied. DESIGN: This was a two-group correlational design with additional statistical assessment of subgroup differences. Each group was interviewed and information obtained on a standard disability preference task, attributions for playmate choice, and frequency of contact with disabilities. Parents completed a structured interview. SETTING: Participants were 122 children recruited from Negros, Philippines. PARTICIPANTS: Fifty-four children with craniofacial anomalies (aged 7 to 12 years) were enrolled in the study, and 68 children without any disabilities were recruited from a local school in Bacolod City, Negros, Philippines. MAIN OUTCOME MEASURES: Participants completed a picture-ranking interview of specific physical disabilities and provided their reasons for their play choices and their contact with physical disabilities. RESULTS: The Kendall W correlation was significant for the children with craniofacial anomalies and for those without physical disabilities. Both groups reported lower preferences for disabilities that interfere with play and social interactions. Children depicted with facial anomalies received lower preference, compared with other physical disabilities. Children with craniofacial anomalies who have experienced surgical repair reported more positive rankings for the child depicted with a facial cleft. Sex differences in disability preference were noted. CONCLUSIONS: Children in the Philippines with and without craniofacial differences revealed similarities in preferences to children in several Western (United States) and non-Western countries. Children depicted with facial anomalies received lower preference than other visible physical differences. Children reported both positive and negative explanations for their disability play preferences. Facial differences may result in illogical and negative explanations for social avoidance among children. Similar reactions are noted in other parts of the world.

Parents as distraction coaches during i.v. insertion: a randomized study.

This study investigated the effectiveness of a brief Distraction Education intervention for parents prior to their preschool children's medical procedures. Forty-four preschool children with chronic non-life-threatening conditions were having intravenous catheters (IVs) placed for medical tests. Parent-child dyads were randomized into two groups. The experimental group received Distraction Education prior to IV insertion; the control group received standard care. Data were analyzed for two phases of the IV procedure. Phase 1 was the preparation for needle insertion; Phase 2 began with needle insertion. Experimental group parents used significantly more distraction than did control group parents during both phases (P < 0.001). There were no group differences for child behavioral distress or self-report of pain. There was a trend toward a group by phase interaction for behavioral distress (P = 0.07); more experimental group children showed decreased behavioral distress over time (from phase 1 to phase 2) than did control group children (P = 0.02).

Effects of distraction on children's pain and distress during medical procedures: a meta-analysis.

BACKGROUND: It is difficult to determine the usefulness of distraction to decrease children's distress behavior and pain during medical procedures because many studies use very small samples and report inconsistent findings. OBJECTIVES: To investigate the mean effect sizes across studies for the effects of distraction on young children's distress behavior and self-reported pain during medical procedures. METHOD: Hunter and Schmidt's (1990) procedures were used to analyze 16 studies (total n = 491) on children's distress behavior and 10 studies (total n = 535) on children's pain. RESULTS: For distress behavior, the mean effect size was 0.33 (+/-0.17), with 74% of the variance accounted for by sampling and measurement error. For pain, the mean effect size was 0.62 (+/-0.42) with 35% of the variance accounted for. Analysis of studies on pain that limited the sample to children 7 years of age or younger (total n = 286) increased the amount of explained variance to 60%. CONCLUSIONS: Distraction had a positive effect on children's distress behavior across the populations represented in this study. The effect of distraction on children's self-reported pain is influenced by moderator variables. Controlling for age and type of painful procedure significantly increased the amount of explained variance, but there are other unidentified moderators at work.

Bone up on osteoporosis. Development of the Facts on Osteoporosis Quiz.

PURPOSE: To describe the development of an instrument to measure women's knowledge of osteoporosis based on Orem's self-care theory and the latest clinical research on osteoporosis. SAMPLE: One hundred and four women from four groups including graduate and undergraduate nursing students, sociology students, and a community sample, completed the instrument. METHODS: Items for the instrument were developed from three objectives related to osteoporosis risk factors, known facts and preventive behaviors. There were 34 items on the original instrument. It was content validated by experts and subjected to item analysis. The report contains a copy of the instrument with the theoretical classification and item analysis. FINDINGS: The Facts on Osteoporosis Quiz had a content validity index of .92, a reliability of .83 and a reading level of sixth grade. Item difficulty and item discrimination were used to delete items. The final instrument contains 25 items. CONCLUSION: The quiz is a simple, inexpensive measure that can be used in various settings by nurses to assess women's knowledge of self-care in osteoporosis.

Taking aim at interdisciplinary education for continuous improvement in health care.

Over the last 30 years, nursing faculty have achieved varying levels of success in their efforts to engage in interdisciplinary education. To sharpen the focus, the Institute for Healthcare Improvement sponsored a national demonstration project in which nursing faculty from four universities participated.

Partnership for a nurse practitioner-directed student health primary care center.

Since 1991, the George Mason University Student Health Center (SHC) has been a primary health care center directed by College of Nursing and Health Science (CNHS) nurse practitioner (NP) faculty. This model was planned and implemented through a partnership between the CNHS and Student Services. From September 1991 until the present, the number of student visits has more than doubled, and the offered services have tripled without a comparable increase in budget and with minimal expansion of space. The student population now has access to comprehensive quality primary care services on-site at a relatively small investment per student. The focus of care goes beyond simply managing current health care needs by emphasizing prevention of future health problems, wellness, and quality of life. In addition, negotiations with surrounding specialists have resulted in a prompt and cost-effective referral system as needed by conditions exceeding the capabilities of the SHC providers. Responses to student surveys regarding the quality, availability, and cost of care, as well as the process involved in receiving that care, indicate the highest level of satisfaction among students using these services. The CNHS has a fertile, convenient faculty practice site as well as several clinical placements for NP as well as undergraduate students. This NP faculty-directed SHC offers a cost-effective, consumer-responsive alternative for delivering primary care services to the members of the university community.

Children's attitudes to physical differences among youth from Western and non-Western cultures.

Children with visible physical impairments (cosmetic and orthopedic) are known to experience difficulties in social interaction with peers. Some of these social difficulties are related to attitudes toward visible physical features of children. Several research studies from Western and non-Western countries are reviewed, focusing on children's attitudes toward children with facial disfigurement. Specific social preferences for particular disabilities are noted which are related to cultural and economic factors. Children's attitudes toward facial disfigurement reflect generally low preference for social interaction in the majority of cultures studied. Children's attitudes reflect both positive and negative attributions toward facial disfigurement.

Grief in adults with mental retardation: preliminary findings.

Structured direct interviews of 43 adults with mental retardation were conducted to evaluate how they express grief and deal with loss. In addition, 100 providers, social workers, and clergy were surveyed to assess their views of how adults with mental retardation cope and respond during a grief situation. Adults with moderate to severe mental retardation display grief responses similar to all adults: a mixture of sadness, anger, anxiety, confusion, and pain. Individuals continue to experience emotional turmoil 1 year beyond the initial death and personal loss. Caregivers and professionals were mixed on how long a grief reaction continues before it can be viewed as dysfunctional. Intense behaviors, such as self-injury, were noted by respondents in 10-15% of grief reactions. Ability to "feel" or display emotional behavior during grief is not contingent only on a conceptual level. Common reactions include a depressive response (crying, fatigue, sleep disruption, loss of appetite) of moderate intensity. Adults with significant mental retardation verbalized an understanding of the irreversibility of death, and their responses reflect personal beliefs as well. An unknown group of these adults may have been exhibiting a depressive disorder.

An economic paradigm for nurse practitioner program development.

In 1987 a collaborative nurse practitioner program was developed and implemented by George Mason University, a public institution, and The George Washington University, a private institution. Three economic factors affecting decisions related to the development of the collaborative program are discussed: (1) optimal use of resources, (2) consumer and institutional utility, and (3) demand for the program. Optimal use of resources was based on collaboration in the areas of faculty and administrative resources and existing curriculum, thereby reducing the cost burden at each institution. From the perspective of consumer and institutional utility, the program was structured financially to enhance the well-being of students and both institutions. Finally, the consumer demand for the program was addressed by maintaining the higher proportion of credits at the lower-cost institution, thus enabling more students to afford the program. The success of the institutions in addressing the economic factors noted above can serve as a paradigm for program development in other universities and graduate programs.

Behavioral problems and medication utilization.

Although psychotropic medications are commonly used with older adults who have mental retardation, patterns of medication use for this group are not easily determined. Our objective was to explore relations between prescribed psychoactive treatments and rated behavioral difficulties. Adults with moderate mental retardation living in congregate and group care settings were rated by care providers using a standard behavior rating instrument. Older adults demonstrated a tendency toward higher medication utilization. Results indicated higher drug utilization in the larger setting despite the fact that behavior problems and cognitive level was matched across all settings. Medication utilization appears to be related to multiple factors, not only the behavioral or cognitive characteristics of adults with mental retardation.

Improving health care communication for persons with mental retardation.

There has been little effort directed at training health care professionals in behaviors and attitudes that are effective in communicating with persons with mental retardation. Such training would be beneficial not only to assist those with congenital cognitive deficits but for those with acquired central nervous system conditions as well, for example, dementia. Persons with mental retardation are living in community settings in greater numbers and increasingly participating in vocational, residential, and health care programs. Yet, most health care professionals are not routinely offered an opportunity to gain experience interacting with people who have limited ability to express and understand health care information. An education program was focused on health care professionals' use of basic communication skills when providing health information to an adult who is mentally retarded. A self-study instructional text and a 20-minute companion video provided methods of communicating with a patient with mental retardation in medical and dental care settings. Resident physicians, medical students, nurses, and nursing assistants improved their communication skills, knew more about mental retardation, and were more proactive in health care interviews following training. Health care training needs to incorporate educational opportunities focusing on skills to assist special populations. Brief, structured, and interactive skill training in communication offered early in the health care professional's career has positive benefits for the recipient and the provider.

Paradigms for investigating rehabilitation and adaptation to childhood disability and chronic illness.

Significant research perspectives in investigating chronic illness and disability are presented. Historical research conceptualizations in childhood disability are reviewed and newer contexts for evaluating disorder are presented. Future research in childhood illness and disability is directed toward basing investigations on theoretical models and promoting prospective longitudinal programs. Pediatric psychologists are encouraged to consider more collaborative efforts to move the field forward systematically.