A pilot feasibility study of massage to reduce pain in people with spinal cord injury during acute rehabilitation.

OBJECTIVE: To determine the feasibility of conducting a randomized controlled trial of massage therapy for patients with a new spinal cord injury (SCI) during acute inpatient rehabilitation. DESIGN: A pilot single-center, randomized, single-blind, cross-over clinical trial. SETTING: Free-standing, not-for-profit, comprehensive rehabilitation center specializing in SCI rehabilitation. PARTICIPANTS: Forty adults ages 18 years and older undergoing acute rehabilitation following an SCI reporting any type of pain. INTERVENTION: Rehabilitation nurses trained to give broad compression massage (BCM) and a control light contact touch (LCT) treatments. Participants were randomized to receive either BCM or LCT first, in six 20-min treatment sessions over 2 weeks, with a 1-week washout between the 2-week treatment periods. MAIN OUTCOME MEASURES: Primary outcomes were changes in pain intensity and in fatigue, measured daily. Secondary outcomes included depressive symptoms measured by the Patient Health Questionnaire-9 (PHQ-9) and an assessment of pain medication usage. RESULTS: Pain intensity was higher at baseline and reduced more in the LCT-first group compared with the BCM-first group in period 1 (P=0.014), although this pattern was not found in period 2 (P=0.58). LCT and BCM groups did not significantly differ on any secondary measures except PHQ-9. CONCLUSIONS: This study demonstrates the feasibility of using rehabilitation nurses to provide tactile therapy to patients with an SCI and suggests a model for controlled clinical trials examining the efficacy of massage therapies. Although efficacy was difficult to assess, BCM was safe and well tolerated.

Assessment of the in vivo immunosuppressive activity of the major cyclosporine metabolite by leukemia allograft rejection.

AM1 (M17) is the major metabolite of cyclosporine found in the blood of human transplant recipients, and trough levels of this derivative exceed those of the parent compound approximately two-fold. Studies performed in vitro indicate that AM1 retains only 10-20% of the biological activity of the parent compound, but very little is known about its in vivo immunosuppressive effects. We therefore developed a rapid and sensitive method, based on the rejection of allogeneic L1210 (H-2d) leukemia cells by C57BL/6 (H-2b) mice, to assess the immunosuppressive activity of AM1 in vivo. Rejection of the leukemia allograft was determined by analyzing the spleens from mice injected intravenously with 10(5) L1210 cells for the presence of H-2Kd-positive cells by flow cytometry using an FITC-conjugated monoclonal anti-H-2Kd antibody. Nonimmunosuppressed mice rejected the allogeneic cells and survived indefinitely. Spleens from these mice were virtually free of H-2Kd-positive cells (0.51 +/- 0.21%) by day 7. In contrast, C57BL/6 mice treated with 10 mg/kg/day s.c. of CsA all died from the L1210 challenge (mean survival time of 9 +/- 1 days). Spleens from mice treated in this manner contained 11.02 +/- 3.31% H-2Kd-positive cells on day 7. There was a direct correlation between the dose of CsA administered (7.5-50 mg/kg/day) and the percentage of H-2Kd-positive cells in the spleen. We then compared the immunosuppressive activity of AM1 and CsA in this model. AM1 was purified from the urine of CsA-treated renal allograft recipients by a combination of preparative adsorption-desorption chromatography and preparative elution high-performance liquid chromatography. AM1 at a dose of 10 mg/kg/day exhibited no demonstrable immunosuppressive effect, and trough levels of AM1 on day 7 were only 36 +/- 4 ng/ml. Increasing the dose of AM1 to 50 mg/kg/day resulted in only 1.05 +/- 0.16% H-2Kd-positive cells in the spleens (P = NS) and a mean trough level of 221 +/- 27 ng/ml. In contrast, mice treated with 50 mg/kg/day of CsA exhibited 17.7 +/- 2.9% H-2Kd-positive cells in their spleens and a mean trough CsA level of 3036 +/- 277 ng/ml. The half-life of a single subcutaneous dose of 10 mg/kg of AM1 (4.6 hr) was significantly shorter than that of CsA (9.7 hr) in mice. Compared with CsA, the lack of immunosuppressive effect of AM1 in vivo therefore appears to be due to a combination of decreased immunosuppressive activity and increased rate of clearance in mice.

The distribution of six enzymes of oxidative metabolism along the rat nephron.

Using quantitative methods, citrate synthase (CS), fumarase, beta-hydroxyacyl-coenzyme A (CoA) dehydrogenase (beta OAC), 3-keto-acid CoA transferase (KCT), malic dehydrogenase (MDH), and malic enzyme were measured in seven defined parts of the nephron and in thin limb and papilla areas dissected from freeze-dried microtome sections of rat kidney. The results not only show a wide range of activity along the nephron for each of the enzymes, but that the proportions between the enzymes vary markedly among the different parts of the nephron. This suggests the existence of major regional differences in the capacity to oxidize specific metabolites. The ratio between two citrate cycle enzymes, fumarase and CS, was 4- or 5-fold higher in proximal segments than in the glomerulus or thin limb areas. The ratio between beta OAC (an enzyme of fatty acid oxidation) and CS was 3- to 5-fold higher in the middle proximal segments than in glomeruli or thin limb and papilla areas. The key enzyme for ketone body metabolism, KCT, was essentially confined to the thick tubule segments. Malic enzyme, in contrast to the other five enzymes, was highest in the proximal straight segments. New methods, sufficiently sensitive for this histochemical study, are described for malic enzyme and 3-keto-acid CoA transferase.

IMDA/retro-Mannich approach to cis-perhydroquinoline Lycopodium alkaloids: asymmetric synthesis of (+)-luciduline.

[formula: see text] The first chiral auxiliary mediated asymmetric synthesis of the naturally occurring Lycopodium alkaloid (+)-luciduline has been accomplished. Key steps include an IMDA reaction of a chiral dihydropyridine, a subsequent retro-Mannich ring opening, and a novel cationic reductive cyclization reaction.

Investigating sun-damaged skin and actinic keratosis with optical coherence tomography: a pilot study.

Actinic Keratosis (AK) arises from sun-damaged skin and is the first clinical manifestation in the multistep process of skin carcinogenesis to invasive squamous cell carcinoma. Thus, it is an ideal target for chemopreventive efforts. Noninvasive measures of AK severity are needed to assess the efficacy of chemoprevention agents. We performed a pilot study on 20 participants to investigate the OCT appearance of sun-protected skin of the upper inner arm as well as sun-damaged skin and early AKs of the dorsal forearms, and to determine if features or quantitative measures in Optical Coherence Tomography (OCT) images could be used to reliably differentiate between these categories. OCT images of upper inner arm (normal appearing skin) showed skin layers and features (stratum corneum, epidermis, dermis, blood vessels) seen in previous studies; additionally in this participant group the subcutaneous fat layer was usually identified. Sun-damaged skin was characterized by increased signal in the epidermis and rapid attenuation of light. AKs were diverse in appearance but frequently characterized by high surface reflection, the presence of a low-signal band in the stratum corneum, and heterogeneous appearance in the epidermis/dermis. Significant differences were found between skin categories using measures of stratum corneum and epidermal/dermal depths and intensities. The presence of a dark band in the stratum corneum was 79% sensitive and 100% specific for AK. This study indicates that OCT holds promise as a useful technique for identifying and characterizing AKs and monitoring their response to chemoprevention agents.

A call to action. Violent deaths are preventable when information is available.

Collecting these variables, along with routine EMS data, will enhance analysis of the interpersonal violence problem. To assume that this information will be obtained further along in the health-care delivery chain jeopardizes its validity, since there is a likelihood that the story may change. Surveillance or ongoing data collection allow for better estimates and enhanced knowledge about the cost of violence to the health-care system. Timely data are needed to identify important shifts in injury patterns, as well as newly emerging problems. For example, a community may observe an increase in the use of baseball bats as weapons. That information could become vital to prevention. As EMS providers, you are in a unique position to augment public-health surveillance of interpersonal violence by virtue of the fact that you are often the first on scene and can collect data that may not be routinely collected. Without this type of information, planning, implementation and evaluation of successful violence prevention reduction efforts continue to present a major challenge to public health systems.

Supporting operational decision making.

The collection and processing of information is a source of power. This fact is true especially in the health care industry. The apparent lack of information related to operational decisions in the health care industry is cause for concern. Data envelopment analysis (DEA) provides information regarding efficiency of resource utilization. This article reports on the use of DEA to measure relative technical efficiency of nursing units and the level of association between efficiency scores and the presence of selected operational characteristics. We found a statistically significant association between efficiency and two of the selected characteristics. Although nursing units are used to illustrate the application of the technique, DEA can be applied to any operational unit of a health care organization. However, we conclude that information systems and a minimum data set are essential to optimizing utilization of a such techniques.

Religion in the clinic: the role of physician beliefs.

BACKGROUND: Although studies have identified physician beliefs that may cause them to avoid spiritual topics in the clinic (eg, lack of time), it is unknown to what extent these beliefs predict behavior. The purpose of the present study was to identify physician beliefs about religion and medicine that predict attention to religious issues in the clinic. METHODS: The study was cross-sectional and correlational. Seventy-eight physicians completed a self-report survey of religious behavior in the clinic and beliefs about religion and medicine. RESULTS: Most physicians do not initiate religious discussions with patients, though a majority accept a link between religion and health. Physician personal discomfort with addressing religious topics was the sole multivariate predictor of clinical religious behavior. Time, role definition, health relevance of religion, and physician religiousness were not significant predictors. CONCLUSIONS: Avoidance of religion in the clinic may be primarily belief-based. Future research is needed to examine the role of medical education in creating and/or maintaining these beliefs.

Effect of salicylhydroxamic acid on endosperm strength and embryo growth of Lactuca sativa L. cv Waldmann's Green seeds.

Salicylhydroxamic acid (SHAM) stimulated germination of photosensitive lettuce (Lactuca sativa L. cv Waldmann's Green) seeds in darkness. To determine whether SHAM acts on the embryo or the endosperm, we investigated separately effects of SHAM on growth potential of isolated embryos as well as on endosperm strength. Embryo growth potential was quantified by incubating decoated embryos in various concentrations of osmoticum and measuring subsequent radicle elongation. Growth potential of embryos isolated from seeds pretreated with 4 millimolar SHAM was equal to that of untreated controls. Rupture strength of endosperm tissue excised from seeds pretreated with SHAM was 33% less than that of controls in the micropylar region. To determine if the embryo must be in contact with the endosperm of SHAM to weaken the endosperm, some endosperms were incubated with SHAM only after dissection from seeds. Rupture strength of SHAM-treated, isolated endosperms in the micropylar region was 25% less than that of untreated controls. There was no difference in rupture strength in the cotyledonary region of endosperm isolated from seeds treated with SHAM in buffer or buffer alone. SHAM therefore stimulates germination not by enhancing embryo growth potential, but by weakening the micropylar region of the endosperm enclosing the embryo.

Preparative chromatographic purification of cyclosporine metabolites.

Polar and primary metabolites of cyclosporin A (CsA) have successfully been isolated by a novel separation protocol. An efficient, easy-to-scale-up chromatographic adsorption/desorption operation recovers polar and primary CsA metabolite pools from large volumes of urine; purified CsA metabolites are subsequently obtained by high-resolution preparative elution chromatography of the semipurified metabolite pools. Separations performed on a semipreparative scale [with a 250 x 9.4 mm (i.d.) reversed-phase HPLC column] yielded microgram quantities of CsA metabolites at > 97% purity, as determined by fast atom bombardment mass spectrometry. These separations also yielded two previously unreported CsA metabolites, similar to AM1A but with an additional hydroxylation. The yield of metabolites was increased to several milligrams by performing the separations with a preparative-scale [250 x 21.2 mm (i.d.)] reversed-phase column. The production rate of purified primary CsA metabolites was greatly increased by performing the separation with the preparative-scale column under conditions of severe mass overloading. In a single chromatographic run, we successfully isolated 11.0 and 5.0 mg of AM1 and AM1c, respectively, at a purity of > 97%. As expected, this increase in the yield of purified metabolites was accompanied by a decrease in the overall recovery. This separation scheme enables the rapid processing of large volumes of urine for isolation of the milligram quantities of CsA metabolites necessary to assess their biological activity. The procedure is applicable to small- or large-scale metabolite isolation and provides a ready source of purified metabolites for in vitro and whole-animal studies.

Salicylhydroxamic acid potentiates germination of 'Waldmann's Green' lettuce seed.

A combination of salicylhydroxamic acid (SHAM) + cyanide (CN) is known to stimulate dark germination of Lactuca sativa L. seeds. Further studies were done to characterize SHAM and CN action in stimulating dark germination of lettuce seed. Germination was stimulated slightly by either SHAM or CN, whereas when SHAM and CN were combined germination was greatly enhanced. Treatment of seeds with SHAM + CN only during the first 8 hours of hydration stimulated germination as much as did treatment for 72 hours. During the first 8 hours of incubation in SHAM + CN, potentiation (i.e. domancy-breaking) of germination occurs. SHAM alone stimulated potentiation nearly to the level of SHAM + CN but inhibited subsequent radicle elongation, thereby decreasing germination when present for 72 hours. Oxygen must be present for SHAM or SHAM + CN to potentiate dark germination. The ability of SHAM and SHAM + CN to potentiate germination is influenced by O2 concentration and the timing of chemical treatment.

The use of proxies in community integration research.

OBJECTIVE: To assess the level of agreement between persons with various disabilities and their proxies in reporting community integration outcomes using the Craig Handicap Assessment and Reporting Technique (CHART). DESIGN: Reliability study. SETTING: Participants living in the community for a minimum of 6 months after onset of disability or completion of inpatient rehabilitation. PARTICIPANTS: Persons (n = 983) with disability resulting from amputation, burn, multiple sclerosis, spinal cord injury (SCI), stroke, or traumatic brain injury and their self-selected proxies. INTERVENTIONS: Telephone interview of subjects (FIM instrument, CHART); proxies (CHART). FIM instrument assesses the degree of assistance with physical and cognitive subscales; CHART measures community integration in 6 subscales: physical, cognitive, and economic independence, and mobility, social integration, and occupation. MAIN OUTCOME MEASURES: Intraclass correlation coefficients (ICCs) were used to assess participant-proxy agreement, and stepwise multiple regressions were used to identify patterns of difference in agreement based on disability type and demographic variables. RESULTS: Thirty-seven of the 38 items examined for the entire sample yielded moderate to strong ICCs. Multiple regression analyses indicated that proxies overrated participants with severe functional cognitive disabilities on the mobility subscale (p < .001), overrated participants with less than a high school education on the total CHART score (p < .01), and underrated participants with SCIs on the occupation subscale (p < .01). Differences in all cases, however, were less than 6 points out of a possible score of 100 per subscale. CONCLUSIONS: Participant-proxy agreement across the 6 disability groups provided evidence in support of the inclusion of proxy data for persons with various types of disabilities in community integration research.

A framework for: what can and should society do?

Researchers strive to better understand the critical periods of brain development. Findings generate clearer descriptions of what the critical periods are and suggest that stress, aggression, and violent behavior affect the development process. But the question remains as to what can and should society do to nurture children through these periods and to support their continued growth and development. Operation Peace in Philadelphia, an urban community-based, violence prevention/reduction initiative using the principals of public health, represents a framework for generating fresh attitudes and innovative support systems that will nurture children through the critical periods of brain development and beyond. This framework enhances understanding of the complexities of societal issues such as violent behavior and uncovers and offers communal solutions. It is a link between research and its practical application--what society can do. Society's challenge echoes Operation Peace's challenge to use the combined strengths of scientific knowledge, multidisciplinary skills, sustained commitment, cultural vitality, community support, and political will to enable youth to achieve their potential, via full and active lives.

Cost of traumatic spinal cord injury in a population-based registry.

This prospective study examines a population based cohort of 115 Coloradans identified as having an acute traumatic spinal cord injury by the Spinal Cord Injury Early Notification System in 1989. Comprehensive medical cost and complication data were collected for the first 2 years of survival. Unlike previous cost studies, this group represents the broad spectrum of spinal cord injured persons, reflected in a truly population based sample. Nearly 22 million dollars were spent during the first 2 years post injury on behalf of these Coloradans. Care provided to the 27 persons with Frankel A, B or C tetraplegia accounted for $10.9 million (50%); $7.6 million (35%) was spent providing care for the 36 people with Frankel A, B or C paraplegia; and the remaining $3.3 million (15%) was required for services provided to the 52 persons who had resolved to either Frankel D or E at acute care discharge. Of the $6.3 million that was spent post hospital discharge, $2.5 million (39%) is directly attributable to in-home care, and another $2.0 million (32%) is directly attributable to secondary medical complications. The most expensive complications occurred in the neurological, skin, respiratory and orthopedic body systems.

Measuring participation across impairment groups using the Craig Handicap Assessment Reporting Technique.

OBJECTIVE: To assess the efficacy, across a range of disability groups, of the Craig Handicap Assessment and Reporting Technique (CHART), a measure of societal participation. DESIGN: Cross-sectional analysis survey methodology. A total of 1110 community-based, nonhospitalized Coloradans with spinal cord injury, traumatic brain injury, multiple sclerosis, stroke, burn, or amputation were interviewed twice, 2 wks apart, using the CHART and a single administration of the FIM. RESULTS: Across all impairment groups, the intraclass correlation for the total score and the subscales of CHART-R were high. In addition, the CHART-R discriminated among the impairment categories in a direction that parallels increasing disability. CONCLUSIONS: CHART may be an appropriate measure of handicap for a range of physical or cognitive impairments.

Traumatic brain injury: designing and implementing a population-based follow-up system.

Craig Hospital and the Colorado Department of Public Health and Environment began designing a population-based follow-up system for persons with traumatic brain injury (TBI) in 1994. With funding from the Centers for Disease Control and Prevention, the Colorado TBI Follow-up System addresses the issue, "What happens to persons with TBI after they are discharged from the hospital?" Two methods of data collection are used, medical record review and annual telephone surveys to gather long-term outcomes. The design calls for following all persons hospitalized with severe TBI (defined as any person with inpatient rehabilitation and/or with an Abbreviated Injury Scale [AIS] score for the head of 3 or greater) and a 20% random sample of persons hospitalized with less severe TBI. An expert panel was used to select variables for retrospective abstracting and prospective interviewing. Information obtained from medical records includes data verifying eligibility, diagnoses, radiological results, circumstances of injury, and severity of injury, as well as demographic data. The interview instrument includes questions and scales related to health status, disability, handicap, quality of life, and service utilization. Both methods of data collection have been pilot-tested and are now used routinely in the Colorado TBI Follow-up System.