"Turning up the heat": role of neurotrophic batokines in the postnatal maturation and remodeling of brown adipose tissue in deer mice.

Activation of brown adipose tissue (BAT) thermogenesis impacts energy balance and must be tightly regulated. Several neurotrophic factors, expressed in BAT of adult laboratory rodents, have been implicated in remodeling the sympathetic neural network to enhance thermogenesis [e.g., nerve growth factor (NGF), neuregulin-4 (NRG4), and S100b]. Here, we compare, to our knowledge, for the first time, the relative roles of three neurotrophic "batokines" in establishing/remodeling innervation during postnatal development and adult cold stress. We used laboratory-reared Peromyscus maniculatus, which rely heavily on BAT-based thermogenesis for survival in the wild, beginning between postnatal days (P) 8 and 10. BAT sympathetic innervation was enhanced from P6 to P10, and exogenous NGF, NRG4, and S100b stimulated neurite outgrowth from P6 sympathetic neurons. Endogenous BAT protein stores and/or gene expression of NRG4, S100b, and calsyntenin-3ß (which may regulate S100b secretion) remained high and constant during development. However, endogenous NGF was low and ngf mRNA was undetectable. Conditioned media (CM) from cultured P10 BAT slices stimulated neurite outgrowth from sympathetic neurons in vitro, which was inhibited by antibodies against all three growth factors. P10 CM had significant amounts of secreted NRG4 and S100b protein, but not NGF. By contrast, BAT slices from cold-acclimated adults released significant amounts of all three factors relative to thermoneutral controls. These data suggest that although neurotrophic batokines regulate sympathetic innervation in vivo, their relative contributions differ depending on the life stage. They also provide novel insights into the regulation of BAT remodeling and BAT's secretory role, both of which are critical to our understanding of mammalian energy homeostasis.NEW & NOTEWORTHY In altricial Peromyscus mice, the developmental shift to endothermy accompanies the establishment of the brown adipose tissue sympathetic neural network. Cultured slices of neonatal BAT secreted high quantities of two predicted neurotrophic batokines: S100b and neuregulin-4, but surprisingly low levels of the classic neurotrophic factor, NGF. Despite low NGF, neonatal BAT-conditioned media was highly neurotrophic. Cold-exposed adults use all three factors to dramatically remodel BAT, suggesting that BAT-neuron communication is life-stage dependent.

Acute Lower Extremity Fracture Management in Chronic Spinal Cord Injury: 2022 Delphi Consensus Recommendations.

Our objective was to develop a clinical practice guideline (CPG) for the treatment of acute lower extremity fractures in persons with a chronic spinal cord injury (SCI). Methods: Information from a previous systematic review that addressed lower extremity fracture care in persons with an SCI as well as information from interviews of physical and occupational therapists, searches of the literature, and expert opinion were used to develop this CPG. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system was used to determine the quality of evidence and the strength of the recommendations. An overall GRADE quality rating was applied to the evidence. Conclusions: Individuals with a chronic SCI who sustain an acute lower extremity fracture should be provided with education regarding the risks and benefits of operative and nonoperative management, and shared decision-making for acute fracture management should be used. Nonoperative management historically has been the default preference; however, with the advent of greater patient independence, improved surgical techniques, and advanced therapeutics and rehabilitation, increased use of surgical management should be considered. Physical therapists, kinesiotherapists, and/or occupational therapists should assess equipment needs, skills training, and caregiver assistance due to changes in mobility resulting from a lower extremity fracture. Therapists should be involved in fracture management as soon as possible following fracture identification. Pressure injuries, compartment syndrome, heterotopic ossification, nonunion, malunion, thromboembolism, pain, and autonomic dysreflexia are fracture-related complications that clinicians caring for patients who have an SCI and a lower extremity fracture may encounter. Strategies for their treatment are discussed. The underlying goal is to return the patient as closely as possible to their pre-fracture functional level with operative or nonoperative management.

Laboratory evaluation of secondary causes of bone loss in Veterans with spinal cord injury and disorders.

An electronic health record (eHR) review of Veterans with a spinal cord injury and disorder (SCI/D) was conducted to understand the extent to which Veterans Affairs (VA) providers pursue workups for secondary causes of osteoporosis in this population. Laboratory tests for secondary causes were ordered in only one-third of Veterans, with secondary causes identified in two-thirds of those tested, most frequently, hypogonadism and hypovitaminosis D. PURPOSE: To identify workups for secondary causes of osteoporosis in SCI/D and the extent to which subspecialty consultations are sought. METHODS: A total of 3018 prescriptions for an osteoporosis medication (bisphosphonate, calcitonin, denosumab, raloxifene, teriparatide) among 2675 Veterans were identified in fiscal years 2005-2015 from VA administrative databases. Approximately 10% of these prescriptions were selected for eHR review. RESULTS: eHR records of 187 Veterans with a SCI/D who had received pharmacological treatment for osteoporosis were reviewed. Workups for secondary causes of osteoporosis were performed in 31.5% of Veterans (n = 59) with approximately 64.4% of those tested (n = 38) having at least one abnormality. Hypogonadism (52.0% of those tested) and hypovitaminosis D (50.0% of those tested) were the most common secondary causes of osteoporosis identified in this population. Approximately 10% of primary care and SCI providers consulted subspecialists for further evaluation and treatment of osteoporosis. Endocrinologists more frequently performed a workup for secondary causes of osteoporosis compared to other provider specialties. CONCLUSIONS: Screening for secondary causes of osteoporosis, particularly for hypogonadism and hypovitaminosis D, should be considered in patients with a SCI/D.

Dual-energy X-ray absorptiometry and fracture prediction in patients with spinal cord injuries and disorders.

Low T-scores at the hip predict incident fractures in persons with a SCI. INTRODUCTION: Persons with a spinal cord injury (SCI) have substantial morbidity and mortality following osteoporotic fractures. The objective of this study was to determine whether dual-energy X-ray absorptiometry (DXA) measurements predict osteoporotic fractures in this population. METHODS: A retrospective historical analysis that includes patients (n = 552) with a SCI of at least 2 years duration who had a DXA performed and were in the VA Spinal Cord Disorders Registry from fiscal year (FY) 2002-2012 was performed. RESULTS: The majority of persons (n = 455, 82%) had a diagnosis of osteoporosis or osteopenia, with almost half having osteoporosis. BMD and T-scores at the lumbar spine were not significantly associated with osteoporotic fractures (p > 0.48) for both. In multivariable analyses, osteopenia (OR = 4.75 95% CI 1.23-17.64) or osteoporosis (OR = 4.31, 95% CI 1.15-16.23) compared with normal BMD was significantly associated with fractures and higher T-scores at the hip were inversely associated with fractures (OR 0.73 (95% CI 0.57-0.92)). There was no significant association of T-scores or World Health Organization (WHO) classification with incident fractures in those with complete SCI (p > 0.15 for both). CONCLUSION: The majority (over 80%) of individuals with a SCI have osteopenia or osteoporosis. DXA-derived measurements at the hip, but not the lumbar spine, predict fracture risk in persons with a SCI. WHO-derived bone density categories may be useful in classifying fracture risk in persons with a SCI.

Risk factors for osteoporotic fractures in persons with spinal cord injuries and disorders.

UNLABELLED: Clinical risk factors for fracture were explored among Veterans with a spinal cord injury. At the end of 11 years of follow-up, the absolute risk of fracture was approximately 20 %. Among the clinical and SCI-related factors explored, a prior history of fracture was strongly associated with incident fracture. INTRODUCTION: Few studies to date have comprehensively addressed clinical risk factors for fracture in persons with spinal cord injury (SCI). The purpose of this study was to identify risk factors for incident osteoporotic fractures in persons with a SCI that can be easily determined at the point of care. METHODS: The Veteran's Affairs Spinal Cord Dysfunction Registry, a national database of persons with a SCI, was used to examine clinical and SCI-related risk factors for fracture. Incident fractures were identified in a cohort of persons with chronic SCI, defined as SCI present for at least 2 years. Cox regression models were used to estimate the risk of incident fractures. RESULTS: There were 22,516 persons with chronic SCI included in the cohort with 3365 incident fractures. The mean observational follow-up time for the overall sample was 6.2 years (median 6.0, IQR 2.9-11.0). The mean observational follow-up time for the fracture group was 3.9 years (median 3.3, IQR 1.4-6.1) and 6.7 years (median 6.7, IQR 3.1-11.0) for the nonfracture group. By the end of the study, which included predominantly older Veterans with a SCI observed for a relatively short period of time, the absolute (i.e., cumulative hazard) for incident fractures was 0.17 (95%CI 0.14-0.21). In multivariable analysis, factors associated with an increased risk of fracture included White race, traumatic etiology of SCI, paraplegia, complete extent of SCI, longer duration of SCI, use of anticonvulsants and opioids, prevalent fractures, and higher Charlson Comorbidity Indices. Women aged 50 and older were also at higher risk of sustaining an incident fracture at any time during the 11-year follow-up period. CONCLUSIONS: There are multiple clinical and SCI-related risk factors which can be used to predict fracture in persons with a SCI. Clinicians should be particularly concerned about incident fracture risk in persons with a SCI who have had a previous fracture.

Surgical compared with nonsurgical management of fractures in male veterans with chronic spinal cord injury.

STUDY DESIGN: Retrospective review of a clinical database. OBJECTIVES: To examine treatment modalities of incident appendicular fractures in men with chronic SCI and mortality outcomes by treatment modality. SETTING: United States Veterans Health Administration Healthcare System. METHODS: This was an observational study of 1979 incident fractures that occurred over 6 years among 12 162 male veterans with traumatic SCI of at least 2 years duration from the Veterans Health Administration (VA) Spinal Cord Dysfunction Registry. Treatment modalities were classified as surgical or nonsurgical treatment. Mortality outcomes at 1 year following the incident fracture were determined by treatment modality. RESULTS: A total of 1281 male veterans with 1979 incident fractures met inclusion criteria for the study. These fractures included 345 (17.4%) upper-extremity fractures and 1634 (82.6%) lower-extremity fractures. A minority of patients (9.4%) were treated with surgery. Amputations and disarticulations accounted for 19.7% of all surgeries (1.3% of all fractures), and the majority of these were done more than 6 weeks following the incident fracture. There were no significant differences in mortality among men with fractures treated surgically compared with those treated nonsurgically. CONCLUSIONS: Currently, the majority of appendicular fractures in male patients with chronic SCI are managed nonsurgically within the VA health-care system. There is no difference in mortality by type of treatment.

Morbidity following lower extremity fractures in men with spinal cord injury.

UNLABELLED: The Veterans Affairs Spinal Cord Dysfunction Registry from 2002 to 2007 was reviewed to determine whether men with spinal cord injury (SCI) and lower extremity fractures had an increased risk of complications compared to those without fractures. We determined that fractures are associated with significant consequences, particularly during the first month postfracture. INTRODUCTION: Despite increasing longevity, patients with SCI have a substantial number of illnesses and comorbid conditions. Lower extremity fractures are frequent events in these patients. However, whether these fractures are associated with any increased risk of complications in SCI is not certain. The purpose of this report was to determine the impact of lower extremity fractures on morbidities in men with SCI. METHODS: A population-based, nested, case-control (1,027 cases and 1,027 propensity-matched controls) of men enrolled in the Veterans Affairs Spinal Cord Dysfunction Registry from fiscal years 2002 to 2007 was reviewed to determine whether lower extremity fractures were associated with an increased risk for complications. RESULTS: In propensity score models matched for demographic (age, race) and SCI-related injury factors (level/completeness of SCI), Veterans Affairs-service connection status, and comorbidities, at 1 month following the fracture, there was an increased risk for respiratory infections, pressure ulcers, urinary tract infections, thromboembolic events, depression, and delirium (p ≤ 0.03 for all). Over 12 months, the only complication more common in fracture cases was pressure ulcers (p < 0.01), with an absolute difference of less than 2 % when compared to controls. There was no significant increased risk of cardiac arrhythmias at any time examined following fracture (≥0.12). CONCLUSIONS: Lower extremity fractures are associated with significant consequences in men with SCI during the first month postfracture, but they do not persist for a long term, except for pressure ulcers. Targeted interventions to prevent complications should be considered following lower extremity fractures in SCI, particularly in the first month following fracture.

Hypertension and antihypertensive treatment in veterans with spinal cord injury and disorders.

OBJECTIVES: Hypertension (HTN) is an important risk factor for cardiovascular disease, a major cause of morbidity and mortality among people with spinal cord injury and disorders (SCI/D). Our study examined prevalence, associated factors, and pharmacological treatment of HTN in Veterans with SCI/D compared with a matched control group. METHODS: A retrospective review was conducted of Veterans with traumatic SCI/D (TSCI/D; n=6672), non-traumatic SCI/D (NTSCI/D; n=3566) and a matched, non-injured cohort. RESULTS: Over half of patients with TSCI/D (56.6%) had HTN, compared with 68.4% of matched controls (P<0.001). Paraplegic and tetraplegic Veterans with TSCI/D had significantly lower odds of having a HTN diagnosis compared with control (odds ratios (OR)=0.84 (0.77-0.91); OR=0.38 (0.35-0.42)). About 71.8% of patients with NTSCI/D had HTN compared with 72.3% of matched controls (P>0.05). Paraplegic and tetraplegic Veterans with NTSCI/D did not have significantly different odds of a HTN diagnosis compared with control (OR=0.92 (0.79-1.05); OR=0.85 (0.71-1.01)). Adjusted analysis indicates that Veterans with tetraplegia and HTN were less likely to receive antihypertensive therapy (TSCI/D, OR=0.62 (0.53-0.71); NTSCI/D, OR=0.81 (0.66-0.99)). CONCLUSION: HTN appears to be more prevalent in SCI/D Veterans than previously reported. TSCI/D Veterans have a significantly lower prevalence of HTN whereas NTSCI/D Veterans have a comparable prevalence of HTN to those without SCI/D. The level of injury (tetraplegia vs paraplegia) has a large impact on the prevalence of HTN in the traumatic cohort. Subsequent antihypertensive therapy is used less in both TSCI/D and NTSCI/D Veterans with tetraplegia and more in TSCI/D Veterans with paraplegia.

Preventive healthcare use among males with multiple sclerosis.

OBJECTIVES: To understand preventive healthcare use by males with multiple sclerosis (MS). STUDY DESIGN: Cross-sectional survey with secondary comparative data. METHODS: Primary survey data were collected from male veterans with MS (n = 1142) and compared with national surveillance data for a general veteran population (n = 31,500) and a general population (n = 68,357). Analyses compared use by group and identified variables associated with service use by male veterans with MS. RESULTS: More veterans with MS had a cholesterol check (93%) than the general veteran population (89%, P < 0.001) and the general population (78%, P < 0.001). More veterans with MS had received annual influenza vaccination (69%) than the general veteran population (58%, P < 0.001) and the general population (42%, P < 0.001). More veterans with MS (81%) had ever received pneumonia vaccination than the general veteran population (67%) and the general population (51%) (P < 0.001). Colon screening was received by 55% of veterans with MS, 49% of the general veteran population (P < 0.001), and 39% of the general population (P < 0.0001). Fewer veterans with MS (34%) had received a prostate-specific antigen (PSA) test and digital rectal examination than the general veteran population (46%, P < 0.001) and the general population (36%, not significant). In males with MS, variables independently associated with cholesterol checks were: white race [odds ratio (OR) = 3.75] and living in the south (OR = 1.95); variables independently associated with influenza vaccination were increased age (OR = 1.03) and being a non-smoker (OR = 0.55); increased age was independently associated with colon screening (OR = 1.02); variables independently associated with PSA testing were increased age (OR = 1.08) and being employed (OR = 3.31), and being unemployed was independently associated with pneumonia vaccination (OR = 0.16). CONCLUSIONS: More males with MS received several recommended preventive health services (e.g. cholesterol and colon screening, influenza and pneumonia vaccination) than males without MS. The Veterans Health Administration is meeting many prevention needs in males with MS, but there is room for improvement in areas such as reducing disparities in PSA screening and increasing respiratory vaccinations to meet national targets.

Dysfunctional sleep in persons with spinal cord injuries and disorders.

STUDY DESIGN: Cross-sectional survey of veterans with spinal cord injuries and disorders (SCI/D). OBJECTIVES: To describe sleep dysfunction (independent of sleep apnea) in persons with traumatic and non-traumatic SCI/D, and to examine characteristics and health outcomes independently associated with sleep dysfunction unrelated to sleep apnea. SETTING: Seven Veterans Affairs SCI care facilities in the United States. METHODS: Mailed cross-sectional survey with follow-up calls completed by end of 2008. Bivariate analyses to compare measures outcomes in persons with SCI/D who were dysfunctional sleepers vs those who were not. Multivariate logistic regression used to identify variables independently associated with dysfunctional sleep in veterans with SCI/D. RESULTS: Overall, 49% of the sample had sleep dysfunction unrelated to sleep apnea. In this subgroup, bivariate analyses showed that a greater proportion of dysfunctional sleepers than non-dysfunctional sleepers were current smokers, had problems with drinking alcohol, hypertension, asthma, chronic obstructive pulmonary disease (COPD) and problematic weight gain. Variables independently associated with higher odds of dysfunctional sleep included white race, being a current smoker, problems with drinking alcohol, asthma, COPD and problematic weight gain. CONCLUSION: Consistent with epidemiological evidence for the general population, we found significant associations of sleep dysfunction with weight gain, smoking, alcohol misuse and select chronic conditions (COPD, asthma). Sustained sleep dysfunction may contribute to health deterioration and mortality, highlighting the need to address the high prevalence of sleep dysfunction (independent of sleep apnea) in persons with SCI/D. In particular, efforts aimed at modifying problematic weight gain, alcohol misuse and smoking are warranted in this cohort to improve sleep.

Transarterial chemoembolization for HCC in patients with extensive liver transplantation waiting times.

The treatment of hepatocellular cancer (HCC) with transarterial chemoembolization (TACE) prior to orthotopic liver transplant (OLT) is of increasing importance due to the rise in HCC incidence and donor shortage. This single-center study examines 28 patients treated with TACE and 7 patients not treated with TACE, with HCC prior to OLT between 1999 and 2008. The overall 1- and 5-year survival of all transplanted patients with HCC was 94% (33 of 35) and 80% (28 of 35). There was no difference in survival (P = .99) between patients who underwent transplantation immediately (median 95 days) and patients who had significantly longer wait times (median 308 days) when treated with TACE. During extensive wait times for OLT, TACE can be used to keep patients with HCC on the waiting list by preventing tumor progression, with similar outcomes compared with those who underwent transplantation immediately.

Bloodstream infections and setting of onset in persons with spinal cord injury and disorder.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: Health-care-associated (HCA) bloodstream infection (BSI) has been shown to be a distinct epidemiologic category in the general adult population, but few studies have examined specific patient populations. The objective of this study was to assess characteristics associated with BSI that occurred in the hospital (hospital-acquired, HA BSI), from health-care contact outside the hospital (HCA BSI) or in the community (community-acquired, CA BSI) in veterans with spinal cord injury and disorder (SCI&D). SETTING: Two United States Department of Veterans Affairs hospitals. METHODS: All patients with SCI&D with a positive blood culture admitted to study hospitals over a 7-year period (1 October 1997 to 30 September 2004). Demographics, medical characteristics and causative organisms were collected. RESULTS: Four hundred and thirteen episodes of BSI occurred in 226 patients, with a rate of 7.2 BSI episodes per 100 admissions: 267 (64.7%) were HA BSI, 110 (26.6%) were HCA BSI and 36 (8.7%) were CA BSI. Antibiotic resistance was more common in those with HA BSI (65.5%) compared with that in those with HCA (49.1%, P=0.001) and CA BSI (22.2%, P<0.0001). Methicillin resistance in Staphylococcus aureus was highly prevalent; HA BSI (84.5%), HCA BSI (60.6%) and CA BSI (33.3%). CONCLUSION: HCA BSI comprises one-quarter of all BSIs in hospitalized patients with SCI&D. Although those with HCA and CA BSI share similarities, several differences in medical characteristics and causal microorganism are noted. Treatment and management strategies for HCA and CA infections need to vary.

Health-related quality of life for veterans with spinal cord injury.

STUDY DESIGN: Cross-sectional. OBJECTIVES: The objective of this study was to examine the association between the characteristics of individuals with spinal cord injury (SCI) and self-reported health-related quality of life (HRQoL). SETTING: The United States. METHODS: Questions from the Behavioral Risk Factor Surveillance System (BRFSS) survey were sent to veterans with SCI. The analyses included 2302 respondents. Logistic regression analysis was used to examine the association between subject characteristics and the following four measures of HRQoL: frequent physical distress (FPD), frequent mental distress (FMD), frequent depressive symptoms (FDS) and poor or fair self-reported health. RESULTS: Approximately 19% of the respondents reported FMD, 27% reported FPD, 17% reported FDS and 29% reported poor or fair health. Veterans who self-reported chronic illnesses, had higher odds of reporting FPD, FMD, FDS and poor or fair health than veterans who did not report chronic illnesses. Smoking was significantly associated with decreased HRQoL. Older veterans had higher odds of reporting poor or fair health and FPD than younger veterans. Higher levels of education were associated with lower odds of FMD, FDS and poor or fair health. CONCLUSIONS: Chronic illnesses and smoking have a substantial effect on HRQoL for persons with SCI, suggesting the importance of continued efforts to improve smoking cessation methods and to treat and prevent chronic conditions.

The receptor tyrosine kinase EphB4 is overexpressed in ovarian cancer, provides survival signals and predicts poor outcome.

EphB4 is a member of the largest family of transmembrane receptor tyrosine kinases and plays critical roles in axonal pathfinding and blood vessel maturation. We wanted to determine the biological role of EphB4 in ovarian cancer. We studied the expression of EphB4 in seven normal ovarian specimens and 85 invasive ovarian carcinomas by immunohistochemistry. EphB4 expression was largely absent in normal ovarian surface epithelium, but was expressed in 86% of ovarian cancers. EphB4 expression was significantly associated with advanced stage of disease and the presence of ascites. Overexpression of EphB4 predicted poor survival in both univariate and multivariate analyses. We also studied the biological significance of EphB4 expression in ovarian tumour cells lines in vitro and in vivo. All five malignant ovarian tumour cell lines tested expressed higher levels of EphB4 compared with the two benign cell lines. Treatment of malignant, but not benign, ovarian tumour cell lines with progesterone, but not oestrogen, led to a 90% reduction in EphB4 levels that was associated with 50% reduction in cell survival. Inhibition of EphB4 expression by specific siRNA or antisense oligonucleotides significantly inhibited tumour cell viability by inducing apoptosis via activation of caspase-8, and also inhibited tumour cell invasion and migration. Furthermore, EphB4 antisense significantly inhibited growth of ovarian tumour xenografts and tumour microvasculature in vivo. Inhibition of EphB4 may hence have prognostic and therapeutic utility in ovarian carcinoma.

EphB4 receptor tyrosine kinase is expressed in bladder cancer and provides signals for cell survival.

We sought to evaluate the biological function of the receptor tyrosine kinase EphB4 in bladder cancer. All of the nine bladder cancer cell lines examined express EphB4 and the receptor could be phosphorylated following stimulation with its cognate ligand, EphrinB2. Out of the 15 fresh bladder cancer specimens examined, 14 expressed EphB4 with a mean sevenfold higher level of expression compared to adjacent normal urothelium. EphB4 expression was regulated by several mechanisms: EPHB4 gene locus was amplified in 27% tumor specimens and 33% cell lines studied; inhibition of EGFR signaling downregulated EphB4 levels; and forced expression of wild-type p53 reduced EphB4 expression. EphB4 knockdown using specific siRNA and antisense oligodeoxynucleotides molecules led to a profound inhibition in cell viability associated with apoptosis via activation of caspase-8 pathway and downregulation of antiapoptotic factor, bcl-xl. Furthermore, EphB4 knockdown significantly inhibited tumor cell migration and invasion. EphB4 knockdown in an in vivo murine tumor xenograft model led to a nearly 80% reduction in tumor volume associated with reduced tumor proliferation, increased apoptosis and reduced tumor microvasculature. EphB4 is thus a potential candidate as a predictor of disease outcome in bladder cancer and as target for novel therapy.

Patients' perspective on the comprehensive preventive health evaluation in veterans with spinal cord injury.

STUDY DESIGN: Survey research methods. OBJECTIVES: To assess patient satisfaction with the annual comprehensive preventative health evaluation (CPHE) and to determine if the patient's needs were being met. SETTING: Department of Veterans Affairs National Survey, United States. METHODS: A total of 853 subjects with spinal cord injuries participated in a mailed survey regarding the annual CPHE. Subjects were asked about satisfaction with the examination, preferences on how the examination is conducted and whether their needs were being met with the examination. RESULTS: In all, 76% of the subjects that responded to the survey had completed a CPHE within the previous year. Subjects cited getting their medication and supplies refilled and talking to the doctor as the top two reasons for completing the evaluation. Subjects indicated that they would most like to discuss their muscle strength and weakness, bladder care, chronic pain, digestion and bowel care issues, and equipment problems during their evaluation. The majority of subjects (81%) indicated that they were satisfied with the CPHE. Subjects that were satisfied with the CPHE were also more satisfied with other aspects of care as well. CONCLUSION: The majority of respondents had completed a CPHE within the previous year. Most respondents cite health issues related to the spinal cord injury as areas they would most like to discuss during the evaluation. The majority of subjects were satisfied with the conduct of the CPHE.

Management of community-acquired pneumonia in persons with spinal cord injury.

STUDY DESIGN: Retrospective case series. OBJECTIVES: Respiratory disorders are the leading cause of death in persons with spinal cord injury (SCI), but the epidemiology and medical management of pneumonia in persons with chronic SCI is not well characterized. We describe the clinical presentation of persons with SCI with community-acquired pneumonia (CAP), characterize its management and compare practice to recommendations for CAP in the general population. SETTING: Three United States Veterans Affairs Medical Centers with specialized SCI services. METHODS: Chart abstraction was performed for all persons with chronic SCI seen at participating centers for treatment of CAP during a 2-year period. Collected data included presenting signs and symptoms, laboratory and imaging results, initial antibiotic therapy, secretion mobilization techniques, in-patient vs outpatient management, length of stay, and mortality. RESULTS: In all, 41 persons with SCI received treatment for CAP during the study period. A total of 32 (78.0%) patients were admitted for treatment; two (4.8%) required intubation and mechanical ventilation. Initial antibiotic coverage met guideline recommendations for only half of inpatients and infrequently provided adequate antipseudomonal coverage. Microbiologic testing was performed on 26 cases (63.4%) and demonstrated a specific pathogen in only five cases (12.2% of total). Three cases (7.3%) died during treatment for CAP, and 16 (42.1%) of 38 CAP survivors died within a median follow-up of 3 years. CONCLUSION: The majority of chronic SCI patients who present to specialized SCI centers with CAP are admitted for treatment. Short-term mortality is comparable to CAP in the general population.

Myosin heavy chain expression in the red, white, and ventricular muscle of juvenile stages of rainbow trout.

Juvenile stages of rainbow trout, smaller parr and older juveniles, termed smolts, show differences in red muscle contractile properties: parr red muscle has faster kinetics and a faster maximum shortening velocity than smolt red muscle. A developmental reduction in the number of MHC isoforms as detected by SDS-PAGE between parr and smolt has also been observed. To investigate whether this shift in contractile kinetics results from differential gene expression, three different MHC cDNA fragments, one each from red, white, and ventricular muscle, were identified. The red muscle and ventricular forms are novel MHCs, and the white muscle form is identical to a published MHC from adult trout white muscle. Tissue and developmental stage-specific expression patterns of these MHC isoforms were examined using isoform-specific RT-PCR. Ventricular muscle typically showed only the ventricular form; 60% parr and 80% smolts expressed the ventricular form only. Approximately half of the white muscle samples of either parr or smolts, 58% and 50%, respectively, expressed only white muscle MHC. Red muscle samples were the most heterogeneous, with red muscle MHC found in combination with either the white or ventricular form or both. Combining samples from the anterior and posterior, 8% of parr red muscle samples expressed solely the red muscle MHC form, and 30% of smolt red muscle samples expressed the red muscle form alone. Variations in the relative contribution of each MHC to the red muscle of parr and smolt may explain observed differences in protein composition and contractile properties. J. Exp. Zool. 290:751-758, 2001.

Dual cell seeding and the use of zymogen tissue plasminogen activator to improve cell retention on polytetrafluoroethylene grafts.

OBJECTIVE: The purpose of this study was to enhance the retention of seeded endothelial cells (EC) on prosthetic vascular grafts. Dual-layer EC and smooth muscle cell (SMC) seeding and gene transfer of a zymogen tissue plasminogen activator gene (tPA) into seeded EC were studied. METHODS: Polytetrafluoroethylene (PTFE) grafts were precoated with fibronectin, seeded with SMC followed by EC a day later, and then, 24 hours later, exposed to an in vitro flow system for 1 hour. Cell retention rates were determined for grafts seeded with EC only, a dual layer of EC on top of SMC, EC transduced with wild-type tPA, and EC transduced with zymogen tPA. RESULTS: Seeding efficiency of PTFE pretreated with fibronectin was 260 +/- 8 cell/mm(2). After exposure to flow, only 39% +/- 14% of the EC were retained when EC were seeded alone, whereas 73% +/- 22% of EC remained on grafts when EC were seeded on top of SMC (P <.001, n = 10). The enzyme activity of a mutant zymogen tPA in absence of fibrin was 14 +/- 1 IU/mL, which is 3.6-fold lower than that in the presence of fibrin (50 +/- 19 IU/mL), whereas fibrin has no effect on the wild-type tPA activity. EC expressing a high level of wild-type tPA had a lower retention rate (37%) when compared with normal EC (45%). EC expressing the mutant zymogen tPA had an improved retention rate (54%, P =.001, n = 10) in absence of fibrin, whereas its retention rate was reduced to 43% when the cells were exposed to fibrin. CONCLUSION: SMC seeded between EC and PTFE improves EC retention in vitro. Transduction of zymogen tPA increases thrombolytic ability of seeded cells with less adverse impact on cell retention than wild-type tPA.