The effects of an anabolic agent on body composition and pulmonary function in tetraplegia: a pilot study.

STUDY DESIGN: Prospective repeated-measures longitudinal study. OBJECTIVES: To determine if an 8-week course of an oral anabolic steroid can positively effect body composition or pulmonary function in healthy individuals with chronic tetraplegia. SETTING: United States. METHODS: Oxandrolone (20 mg per day) was administered for 8 weeks to 10 men with motor complete tetraplegia. Dual X-ray absorptiometry scans, pulmonary function tests (PFTs), serum lipids and liver function tests (LFTs) were obtained at baseline, 4, 8, 12 and 20 weeks. To analyze change over time, a repeated measures General Linear Model and nonparametric tests were utilized. RESULTS: Following treatment, total lean body mass (LBM) increased 1.9% and LBM of the arms increased 5.4%. Total body fat decreased 1.5%, and increased 3.9% in the arms and, on average, combined measures of PFTs improved 2.2%. High-density lipoprotein cholesterol decreased 31.8%, low density lipoprotein cholesterol increased 41.2%, and LFTs increased 9.7-65.6% while on therapy but all trended to baseline at 20 weeks. CONCLUSION: Baseline body composition was characterized by a high proportion of fat and a body mass index that underestimated chronic disease risk. Treatment with oxandrolone was associated with modest improvements in PFTs and in arm and total body LBM. Unfavorable changes in serum lipids and LFTs indicate that reported benefits of using oxandrolone in this population must be carefully weighed against potential adverse effects.

Modafinil for treatment of fatigue in post-polio syndrome: a randomized controlled trial.

OBJECTIVE: To determine if modafinil can improve fatigue in patients with post-polio syndrome. METHODS: We used a randomized, placebo-controlled crossover trial. Intervention with modafinil (400 mg/day) and placebo occurred over 6-week periods. Primary endpoint (fatigue) was assessed using the Fatigue Severity Scale as the main outcome measure. Other measures included the Visual Analog Scale for Fatigue and the Fatigue Impact Scale. Secondary endpoint (health-related quality of life) was assessed using the 36-Item Short-Form. Analysis of variance for repeated measures was applied to assess treatment, period, and carryover effects. RESULTS: Thirty-six patients were randomized, 33 of whom (mean age: 61 years) completed required interventions. Treatment with modafinil was safe and well-tolerated. After adjusting for periods and order effects, no difference was observed between treatments. CONCLUSION: Based on the utilized measures of outcome modafinil was not superior to placebo in alleviating fatigue or improving quality of life in the studied post-polio syndrome population.

Use of a faculty investment model to attain the goals of a college of nursing.

Driven by demands for fiscal prudence, new services, and an orderly transition as aging faculty approach retirement, a new model for administrative planning and decision making was tested. In its first year of using an investment model, a private, 600+ student, College of Nursing was able to achieve a labor savings of 10 percent, an enhancement of revenue of 3 percent, and a human capital pool equal to 12 percent of total full-time faculty equivalents. The model, which includes the integration of strategic planning, benchmarking, continuous quality improvement, and management by objectives, was accomplished by taking three investment steps. The steps included goal determination, market understanding, and resource allocation. Investment activity distribution and work determination frameworks were developed as a result of the commitment to the investment process. Suggestions for the future include the need to continue to reorient administrative and faculty thinking as definitions of the educational enterprise evolve.

The John Stanley Coulter lecture. The power of compassion and caring in rehabilitation healing.

Rehabilitation of persons with catastrophic illnesses or injuries is a complex, labor-intensive interaction between patients and caregivers. Experiences of overwhelming loss and suffering evoke strong emotions that shape the behavior of both patients and staff during the rehabilitation process. In response to each patient's unique experience, compassion, caring, and other humanistic qualities of the effective caregiver help create a healing environment. Although these qualities are universally accepted as important, they have not been widely studied or critically examined. In recent years, however, there has been a growing interest in use of scientific methods to investigate the impact of "humanistic elements" (ie, complementary and alternative medicine) as therapeutic agents. A review of 7 articles from this literature provides examples of research-based interventions with potential for enhancing outcomes in traditional rehabilitation populations. In today's high-tech impersonal health care system, the use of scientific methods to show that humanistic treatments are effective may represent an important new frontier and opportunity for rehabilitation research.

Erk is essential for growth, differentiation, integrin expression, and cell function in human osteoblastic cells.

Extracellular signal-regulated kinases (Erks), members of the mitogen-activated protein kinase superfamily, play an important role in cell proliferation and differentiation. In this study we employed a dominant negative approach to determine the role of Erks in the regulation of human osteoblastic cell function. Human osteoblastic cells were transduced with a pseudotyped retrovirus encoding either a mutated Erk1 protein with a dominant negative action against both Erk1 and Erk2 (Erk1DN cells) or the LacZ protein (LacZ cells) as a control. Both basal and growth factor-stimulated MAPK activity and cell proliferation were inhibited in Erk1DN cells. Expression of Erk1DN protein suppressed both osteoblast differentiation and matrix mineralization by decreasing alkaline phosphatase activity and the deposition of bone matrix proteins. Cell adhesion to collagen, osteopontin, and vitronectin was decreased in Erk1DN cells as compared with LacZ cells. Cell spreading and migration on these matrices were also inhibited. In Erk1DN cells, expression of alphabeta(1), alpha(v)beta(3), and alpha(v)beta(5) integrins on the surface was decreased. Metabolic labeling indicated that the synthesis of these integrins was inhibited in Erk1DN cells. These data suggest that Erks are not only essential for the growth and differentiation of osteoblasts but also are important for osteoblast adhesion, spreading, migration, and integrin expression.

Nonparalytic polio and postpolio syndrome.

We describe four cases of postpolio syndrome with typical histories, physical examination results, and electrodiagnostic evidence of extensive anterior horn cell disease, as well as the putative pathophysiology of postpolio syndrome in persons with histories of nonparalytic polio and the diagnostic implications for individuals older than 40 yr of age who are experiencing unexplained new weakness, fatigue, and muscle or joint pain. Although the diagnosis of postpolio syndrome traditionally has required a remote history of paralytic polio, many persons such as the ones described here with typical symptoms of postpolio syndrome have no clear history of paralytic disease and are being misdiagnosed. With this in mind, we believe that the diagnostic criteria for postpolio syndrome should be modified to include the following: a history of remote paralytic polio or findings on history, physical examination results, and laboratory studies compatible with poliovirus damage of the central nervous system earlier in life.

Idiopathic thrombocytopenic purpura presenting as postmyringotomy hemorrhage.

Acute idiopathic thrombocytopenic purpura has an annual incidence of about 4 per 100000 children and usually presents after a viral illness with new-onset petechiae, easy bruisability, and, occasionally, mucosal bleeding. It usually follows an uneventful course en route to a spontaneous recovery. We describe a patient with chronic otitis media who developed idiopathic thrombocytopenic purpura as a postmyringotomy complication.

Gastroesophageal reflux: A critical factor in pediatric subglottic stenosis.

Gastroesophageal reflux (GER) plays a causative role in the development of subglottic stenosis (SGS) in children. This study examined the impact of aggressive antireflux therapy on the clinical outcomes of 35 children. Since 1994, 25 children were treated aggressively with omeprazole and cisapride before endoscopic surgical repair of their stenoses, which ranged from Cotton grades 1 to 3. Nine patients became asymptomatic on antireflux therapy alone. Endoscopic repair was performed in 16 patients. Endoscopic repair failed in only 1, who required tracheotomy. Before 1994, all children undergoing endoscopic repair of SGS were treated perioperatively for reflux. Endoscopic repair failed in 10 of the 57 children, and all required tracheotomy. The clinical outcome of these 10 patients after aggressive antireflux therapy is described. Five of the 10 have been decannulated. The role of double pH probe testing and the importance of the pharyngeal probe for monitoring the response to antireflux medication are described. The probe data suggest that in some instances GER may be limited to perioperative stress, but in many cases, especially in premature infants with SGS, GER can persist unabated for years and is not outgrown as the patient matures.

Role of gastroesophageal reflux in pediatric upper airway disorders.

Gastroesophageal reflux (GER) into the laryngopharynx causes or contributes significantly to a variety of upper respiratory problems in children. The pH probe, laryngeal examinations, and broncholveolar lavage results for children with subglottic stenosis, recurrent croup, apnea, chronic cough, laryngomalacia, recurrent choanal stenosis, vocal fold nodules, and chronic sinusitis/otitis/bronchitis were reviewed in an effort to quantify the role of GER in each of these disorders. This review suggests that GER plays a causative role in subglottic stenosis, recurrent croup, apnea, and chronic cough. It is an important inflammatory cofactor in laryngomalacia and possibly in true vocal cord nodules and problematic recurrent choanal stenosis. GER is also an important inflammatory cofactor in chronic sinusitis/otitis/bronchitis but may be the result of chronic illness in the older patients.

The experience of terminating an abusive relationship from an Anglo and African American perspective: a qualitative descriptive study.

A common question asked about abused women is, "Why don't they leave?" This qualitative study explored the experiences of 15 African American and 15 Anglo American women who had terminated abusive relationships. The constant comparative method of analysis of audiotaped interviews revealed a 3-phase process of leaving: being in, getting out, and going on. Participants endured abuse until they could relinquish the fantasy of a happy relationship. Differences in relationship power and public response to abuse distinguished the experiences of Anglo and African American participants. Findings support the notion of leaving as a social process with similarities across both groups. However, critical differences in responses suggest that leaving is a culture-bound experience.

Skeletal casein kinase activity defect in the HYP mouse.

The Hyp mouse, a model for human X-linked hypophosphatemia (XLH), is characterized by phosphate wasting and defective mineralization. Since osteopontin (OPN) is considered pivotal for biological mineralization, we examined the biosynthesis of OPN in osteoblasts of +/Y and Hyp/Y mice. Immunoprecipitation analyses using a specific antibody to OPN revealed that Hyp/Y and +/Y osteoblasts secrete similar levels of OPN as determined by [35S]-methionine biosynthetic labeling, but a reduced phosphorylation was noted after 32P-PO4 biosynthetic labeling. Northern blot hybridization analysis of +/Y and Hyp/Y mice osteoblast mRNAs, using a cDNA probe for mouse OPN, revealed no difference in the steady state levels of osteopontin mRNA. Analysis of casein kinase II activity in +/Y and Hyp/Y mice osteoblast, kidney, heart and liver membrane fractions revealed that casein kinase II activity in the Hyp/Y mice osteoblasts and kidney is only 35%-50%, respectively, of that of the +/Y mice tissues. The accumulated data are consistent with a post-translation defect in the Hyp/Y mouse osteoblast which results in the under-phosphorylation of osteopontin and subsequent under-mineralization of bone matrix.

An intact N terminus is required for the anabolic action of parathyroid hormone on adult female rats.

Intermittent administration of parathyroid hormone (PTH) peptides increases bone density in animal and human models of osteoporosis. In vitro studies have demonstrated that PTH analogs lacking the first two amino acids can stimulate cell proliferation in certain cell systems, whereas fragments with an intact N terminus can be antimitogenic. We have tested whether the truncated PTH(3-38) fragment may be a better "anabolic analog" than PTH(1-38) by monitoring bone density and biomechanical properties of the femur in 6-month-old ovariectomized (OVX) rats. Either PTH fragment was administered subcutaneously (8 micrograms/100 g of body weight) 5 days/week, for 4 weeks, starting 1 week after surgery. During the entire study, untreated OVX rats lost 12.1 +/- 4.4% of their initial bone density. PTH(1-38) reversed the initial bone loss, leading to complete restoration of presurgery values after 4 weeks of treatment. Conversely, administration of PTH(3-38) resulted in 13.2 +/- 5.8% bone loss, while continuous estrogen infusion (10 micrograms/kg/day) prevented bone loss but did not reverse it. Sham-operated animals also experienced significant bone loss in the vehicle and PTH(3-38)-treated groups (-4.5 +/- 6.7%, and -7.6 +/- 2.8%, respectively), whereas a significant gain in bone density (+4.4 +/- 5.6%) was observed in the rats treated with PTH(1-38). A bone quality factor (index of strain energy loss) and the impact strength (resistance to fracture) were 25% and 44% lower in femurs explanted from OVX animals treated with either vehicle or PTH(3-38), compared with sham-operated animals. On the contrary, no difference was observed between OVX and control animals after treatment with PTH(1-38), indicating a preservation of the capacity to withstand mechanical stress. Thus, PTH(1-38) counteracts estrogen-dependent loss of mineral density and bone biomechanical properties and increases bone density in estrogen-replete animals. An intact N terminus sequence is necessary for this anabolic action of PTH.

Post-polio syndrome: historical perspective, epidemiology and clinical presentation.

Paralytic poliomyelitis has plagued mankind for centuries. The incidence of acute paralytic poliomyelitis dramatically declined in 1955 only after the introduction of the inactivated polio vaccine. Post-Polio Syndrome (PPS) was described as early as the 1870s, but was not clearly recognized by the medical community until the early 1980s. This article reviews the history and epidemiology of acute paralytic poliomyelitis, as well as post-polio syndrome, from its early description by Charcot and others in 1875, to the modern roots of PPS research in 1954. Finally, we will describe the presenting features of PPS, in both clinical and population studies which represent two very different 'faces' of post-polio.

Comparison of 22-oxacalcitriol and 1,25(OH)2D3 on bone metabolism in young X-linked hypophosphatemic male mice.

Using a mouse model (Hyp) of human hypophosphatemic vitamin D-resistant rickets [X-linked hypophosphatemia (XLH)], we compared the effects of 22-oxa-1,25-dihydroxyvitamin D3 (OCT) and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on restoring defects in mineral and skeletal metabolism. Hyp/Y mice received OCT or 1,25(OH)2D3 at doses of 0.05-0.25 micron.kg-1.day-1 for 4 wk. OCT normalized serum calcium levels, whereas 1,25(OH)2D3 produced hypercalcemia in Hyp/Y. OCT and 1,25(OH)2D3 also normalized serum phosphate levels and increased urinary calcium levels. Additionally, OCT and 1,25(OH)2D3 reduced elevated urinary pyridinoline levels and suppressed urinary adenosine 3',5'-cyclic monophosphate levels to normal. Bone ash content was low in Hyp/Y, and OCT was more effective than 1,25(OH)2D3 in reversing this defect. Histomorphometric analysis of bone turnover, mineralization rate, and osteoid content demonstrated comparable responses with OCT and 1,25(OH)2D3, although the highest dose of 1,25(OH)2D3 resulted in increased osteoid content and delayed mineralization. OCT appears to be more effective and definitely less toxic than 1,25(OH)2D3 in reversing skeletal lesions in Hyp/Y mice and may prove to be the drug of choice in the treatment of childhood XLH.

Evaluation of bone resorption: a common problem during impaired mobility.

Osteoporosis, the result of an imbalance between bone resorption and bone formation, is a potential problem for the individual with a spinal cord injury because of the immobility commonly associated with this impairment. This study was performed to determine the diagnostic value of a new assay for urinary Pyridinium crosslink (UPyr). Assays were performed on 62 first morning voided and 50 24-hour urine specimens from clients in a bone health clinic. Higher than normal levels of UPyr were observed in females with osteoporosis. UPyr correlated well with urinary hydroxyproline (r = 0.429, p = 0.005; conversely, there was an inverse relationship between bone density and UPyr (r = -0.489, p = 0.01), positive correlation (r = 0.43, p = 0.011) between the 24-hour UPyr and a serum marker of bone resorption. The study confirms that UPyr has the ability to identify states of high bone resorption. This assay should be a welcome addition to the bone health assessment of individuals with risk factors such as impaired physical mobility.

National rehabilitation hospital limb classification for exercise, research, and clinical trials in post-polio patients.

A need exists for an objective classification of polio patients for clinical and research purposes that takes into account the focal, asymmetric, and frequent subclinical nature of polio lesions. In order to prescribe a safe, effective exercise program, we developed a five-level (Classes I-V) limb-specific classification system based on remote and recent history, physical examination, and a four-extremity electrodiagnostic study (EMG/NCS). Class I limbs have no history of remote or recent weakness, normal strength, and a normal EMG. Class II limbs have no history of remote or recent weakness (or if remote history of weakness, full recovery occurred), normal strength and EMG evidence of prior anterior horn cell disease (AHCD). Class III limbs have a history of remote weakness with variable recovery, no new weakness, decreased strength, and EMG evidence of prior AHCD. Class IV limbs have a history of remote weakness with variable recovery, new clinical weakness, decreased strength, and EMG evidence of AHCD. Class V limbs have a history of severe weakness with little-to-no recovery, severely decreased strength and atrophy, and few-to-no motor units on EMG. In a prospective study of 400 limbs in 100 consecutive post-polio patients attending our clinic, 94 (23%) limbs were Class I, 88 (22%) were Class II, 95 (24%) were Class III, 75 (19%) were Class IV, and 48 (12%) were Class V. Guidelines for the use of this classification in a clinical/research setting are presented along with sample case histories and class-specific exercise recommendations.

Communication and control: parent, child, and health care professional interactions during painful procedures.

Through use of a qualitative ethological approach, observations of 17 children who were undergoing 44 painful procedures during cancer diagnosis or treatment were videotaped and analyzed. The children, aged 4 to 18 years, were part of a larger study testing the effectiveness of nonpharmacologic pain management techniques. Analysis of the videotaped observations revealed that several distinct patterns of conversation between caregivers, parents, and children varied greatly among situations. Both child-centered and nonchild-centered communications were demonstrated. During periods of quiet, nonchild-centered behaviors increased. As a child's distress increased, parents actively changed behaviors to redirect verbal support back to the child and to the pain control interventions. Nurses' encouraging parents to be actively involved and physically close during painful treatments may results in less distress and discomfort for the child. In addition, health care professionals need to be aware of the various patterns of child-parent-caregiver interactions and the need to stay focused on the child during painful procedures to enhance the child's ability to cope.