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1.  Age-related prevalence of low testosterone in men with spinal cord injury 
Objective
To describe the relationship of advancing age in persons with chronic spinal cord injury (SCI) on the prevalence of low testosterone in men with SCI compared to historical normative data from able-bodied men in the general population.
Design
Retrospective, cross-sectional study. Two hundred forty-three healthy, non-ambulatory outpatient men with chronic SCI from age of 21 to 78 years were included in this retrospective analysis.
Results
Forty-six percent of men with SCI were identified as having low serum total testosterone concentrations (total testosterone <11.3 nmol/l). The age-related decline in SCI for total serum testosterone concentration was 0.6%/year compared to 0.4%/year in the Massachusetts Male Aging Study. Between the third and eighth decade of life, men with SCI had a 15, 39, 50, 53, 58, and 57% prevalence rate of low serum total testosterone, which is higher than values reported for each decade of life for able-bodied men in the Baltimore Longitudinal Study on Aging.
Conclusion
Compared with the general population, low serum total testosterone concentration occurs earlier in life in men with SCI, at a higher prevalence by decade of life, and their age-related decline in circulating total testosterone concentration is greater. Studies of T replacement therapy in men with SCI should assist in determining the possible functional and clinical benefits from reversing low serum total testosterone concentration.
doi:10.1179/2045772313Y.0000000122
PMCID: PMC4066549  PMID: 24090163
Spinal cord injuries; Testosterone replacement therapy; Paraplegia; Tetraplegia; Aging
2.  Vertical ground reaction force-based analysis of powered exoskeleton-assisted walking in persons with motor-complete paraplegia 
Objective
To use vertical ground reaction force (vGRF) to show the magnitude and pattern of mechanical loading in persons with spinal cord injury (SCI) during powered exoskeleton-assisted walking.
Research design
A cross-sectional study was performed to analyze vGRF during powered exoskeleton-assisted walking (ReWalk™: Argo Medical Technologies, Inc, Marlborough, MA, USA) compared with vGRF of able-bodied gait.
Setting
Veterans Affairs Medical Center.
Participants
Six persons with thoracic motor-complete SCI (T1–T11 AIS A/B) and three age-, height-, weight- and gender-matched able-bodied volunteers participated.
Interventions
SCI participants were trained to ambulate over ground using a ReWalk™. vGRF was recorded using the F-Scan™ system (TekScan, Boston, MA, USA).
Outcome measures
Peak stance average (PSA) was computed from vGRF and normalized across all participants by percent body weight. Peak vGRF was determined for heel strike, mid-stance, and toe-off. Relative linear impulse and harmonic analysis provided quantitative support for analysis of powered exoskeletal gait.
Results
Participants with motor-complete SCI, ambulating independently with a ReWalk™, demonstrated mechanical loading magnitudes and patterns similar to able-bodied gait. Harmonic analysis of PSA profile by Fourier transform contrasted frequency of stance phase gait components between able-bodied and powered exoskeleton-assisted walking.
Conclusion
Powered exoskeleton-assisted walking in persons with motor-complete SCI generated vGRF similar in magnitude and pattern to that of able-bodied walking. This suggests the potential for powered exoskeleton-assisted walking to provide a mechanism for mechanical loading to the lower extremities. vGRF profile can be used to examine both magnitude of loading and gait mechanics of powered exoskeleton-assisted walking among participants of different weight, gait speed, and level of assist.
doi:10.1179/2045772313Y.0000000126
PMCID: PMC3758528  PMID: 23820147
Spinal cord injury; Paraplegia; Rehabilitation; ReWalk™; Assistive technology; Robotic-assisted exoskeletal device; Vertical ground reaction force; Mechanical loading; F-scan™ tekscan; Fourier series
3.  Prediction of limb lean tissue mass from bioimpedance spectroscopy in persons with chronic spinal cord injury 
Background
Bioimpedance spectroscopy (BIS) is a non-invasive, simple, and inexpensive modality that uses 256 frequencies to determine the extracellular volume impedance (ECVRe) and intracellular volume impedance (ICVRi) in the total body and regional compartments. As such, it may have utility as a surrogate measure to assess lean tissue mass (LTM).
Objective
To compare the relationship between LTM from dual-energy X-ray absorptiometry (DXA) and BIS impedance values in spinal cord injury (SCI) and able-bodied (AB) control subjects using a cross-sectional research design.
Methods
In 60 subjects (30 AB and 30 SCI), a total body DXA scan was used to obtain total body and leg LTM. BIS was performed to measure the impedance quotient of the ECVRe and ICVRi in the total body and limbs.
Results
BIS-derived ECVRe yielded a model for LTM in paraplegia, tetraplegia, and control for the right leg (RL) (R2 = 0.75, standard errors of estimation (SEE) = 1.02 kg, P < 0.0001; R2 = 0.65, SEE = 0.91 kg, P = 0.0006; and R2 = 0.54, SEE = 1.31 kg, P < 0.0001, respectively) and left leg (LL) (R2 = 0.76, SEE = 1.06 kg, P < 0.0001; R2 = 0.64, SEE = 0.83 kg, P = 0.0006; and R2 = 0.54, SEE = 1.34 kg, P < 0.0001, respectively). The ICVRi was similarly predictive of LTM in paraplegia, tetraplegia, and AB controls for the RL (R2 = 0.85, SEE = 1.31 kg, P < 0.0001; R2 = 0.52, SEE = 0.95 kg, P = 0.003; and R2 = 0.398, SEE = 1.46 kg, P = 0.0003, respectively) and LL (R2 = 0.62, SEE = 1.32 kg, P = 0.0003; R2 = 0.57, SEE = 0.91 kg, P = 0.002; and R2 = 0.42, SEE = 1.31 kg, P = 0.0001, respectively).
Conclusion
Findings demonstrate that the BIS-derived impedance quotients for ECVRe and ICVRi may be used as surrogate markers to track changes in leg LTM in persons with SCI.
doi:10.1179/2045772313Y.0000000108
PMCID: PMC3739894  PMID: 23941792
Spinal cord injury; Bioimpedance spectroscopy; Lean tissue mass; Extracellular volume; Intracellular volume; Dual-energy X-ray absorptiometry
4.  Low-dose baclofen therapy raised plasma insulin-like growth factor-1 concentrations, but not into the normal range in a predictable and sustained manner in men with chronic spinal cord injury 
Objective
To evaluate, whether once-daily oral baclofen administration increases and/or sustains plasma insulin-like growth factor-1 (IGF-1) concentration in 11 men with chronic spinal cord injury (SCI) and IGF-1 deficiency (i.e. <250 ng/ml).
Design
Prospective, open-label, dose titration study. Baclofen was administered at 20 mg/day for 8 weeks; then increased to 40 mg/day for another 8 weeks. Plasma IGF-1 and self-reported side effects were measured at baseline and every other week for the duration of the study.
Results
The subjects were 43 ± 12 years old, had duration of injury of 20 ± 12 years; eight subjects had a complete motor injury, and eight had paraplegia. Nine of 11 subjects completed the 20 mg/day treatment and 5 subjects completed the 40 mg/day treatment. Plasma IGF-1 levels improved with each baclofen dose; however, only one subject increased from baseline and remained above the targeted physiological range of 250 ng/ml throughout treatment. A significant increase in IGF-1concentration was observed between baseline and week 2 (154 ± 63 vs. 217 ± 69 ng/ml; P < 0.05), weeks 8 and 10 (188 ± 95 vs. 228 ± 93 ng/ml; P < 0.05), and weeks 8 and 16 (188 ± 95 vs. 259 ± 92 ng/ml; P < 0.05). No serious side effects were observed at 20 mg/day; the 40 mg/day dose was less well tolerated.
Conclusion
Baclofen was not effective at sustaining plasma IGF-1 concentrations in the physiological range in men with chronic SCI.
doi:10.1179/2045772312Y.0000000061
PMCID: PMC3739897  PMID: 23941795
Baclofen; Gamma-aminobutyric acid; Insulin-like growth factor-1; Testosterone; Spinal cord injuries; Paraplegia; Tetraplegia; Spasticity
5.  Adaptation of computerized posturography to assess seated balance in persons with spinal cord injury 
Background
The ability to retain or improve seated balance function after spinal cord injury (SCI) may mean the difference between independence and requiring assistance for basic activities of daily living. Compared with assessments of standing and walking balance, seated balance assessments remain relatively underemphasized and under-utilized.
Objective
To optimize tools for assessing seated balance deficits and recovery in SCI.
Design
Cross-sectional observational study of different methods for assessing seated balance function.
Setting
Veterans Affairs Center of Excellence for the Medical Consequences of Spinal Cord Injury.
Participants
Seven able-bodied volunteers, seven participants with chronic motor-complete thoracic SCI.
Interventions
A computerized pressure-plate apparatus designed for testing standing balance was adapted into a seated balance assessment system.
Outcome measures
Seated section of Berg Balance Scale; modified functional reach test; and two posturography tests: limits of stability and clinical test of sensory integration on balance.
Results
Seated posturography demonstrated improved correlation with neurological level of lesion compared to that of routinely applied subjective clinical tests.
Conclusion
Seated posturography represents an appealing outcome measure that may be applied toward the measurement of functional changes in response to various rehabilitation interventions in individuals with paralysis.
doi:10.1179/2045772312Y.0000000053
PMCID: PMC3595960  PMID: 23809527
Spinal cord injuries; Paraplegia; Rehabilitation; Disability; Assistive technology; Berg balance scale; Limits of stability; Modified functional reach test; Posturography
6.  Increased Presence of Cognitive Impairment in Hemodialysis Patients in the Absence of Neurological Events 
American Journal of Nephrology  2011;35(2):120-126.
Background/Aims
Cognitive impairment (CI) is highly prevalent among hemodialysis (HD) patients and is associated with increased morbidity and mortality. The aim was to compare cognitive function in HD patients with no history of stroke or dementia and well-matched controls. Studies are required to determine the impact of HD and chronic kidney disease-specific risks on CI.
Methods
76 outpatients (50 receiving outpatient HD and 26 with normal kidney function matched for age and comorbidity) underwent a cross-sectional observational study. HD patients were well dialyzed and had optimal hemoglobin levels. A battery of eight neuropsychological tests was used. Outcomes included assessment scores of neurocognitive testing and prevalence and subtype of CI.
Results
Compared to controls, HD subjects had significantly lower composite scores for each tested cognitive domain. In each domain except memory, the percentage of subjects with impairment was significantly higher in HD subjects than controls. Differences between the groups were independent of vascular and dementia risk factors. 82% of HD subjects met criteria for CI versus 50% of controls. Non-amnestic subtype of CI was more prevalent in both groups.
Conclusion
Well-dialyzed HD patients with optimized hemoglobin levels and with no history of stroke or dementia performed significantly worse on multiple measures of cognition compared to controls. A higher prevalence of non-memory impairment may suggest an underlying vascular versus neurodegenerative mechanism. HD and chronic kidney disease-specific risk factors may contribute to early CI not readily detected by routine screening methods.
doi:10.1159/000334871
PMCID: PMC3711004  PMID: 22212437
Cognitive impairment; Chronic kidney disease; Hemodialysis
7.  Reproducibility and effect of posture on impulse oscillation parameters in persons with spinal cord injury 
Background
The impulse oscillation system (IOS) offers significant value in the assessment of airway dynamics in persons with spinal cord injury (SCI) because of minimal patient effort but measurement reproducibility in SCI is unknown.
Objective
To evaluate between-day reproducibility and the effect of posture on airway resistance [respiratory resistances at 5 Hz (R5) and 20 Hz (R20)] in subjects with tetraplegia, paraplegia and able-bodied controls.
Methods
Ten subjects with tetraplegia, 10 subjects with paraplegia and 11 able-bodied individuals were evaluated using IOS. Three 30 second trials were obtained in each while in the seated and supine position on Day 1, and repeated on Day 2.
Results
The within-day coefficient of variation (CV%) for R5 and R20 were comparable in the 3 study groups in the seated and supine positions. Compared to controls, the between-day CV% for the combined data was higher in subjects with tetraplegia and paraplegia for R5 seated, and was higher in subjects with tetraplegia for R5 supine.
Conclusions
IOS has applicability to the study of within-day respiratory resistance in SCI. However, performing longer-term studies in subjects with tetraplegia and paraplegia may be problematic because of the greater variability for R5 when compared to able-bodied individuals.
doi:10.1179/2045772311Y.0000000047
PMCID: PMC3240913  PMID: 22330188
Spinal cord injuries; Paraplegia; Tetraplegia; Forced oscillation technique; Airway dynamics; Respiratory resistance; Airway obstruction; Spirometry; Plethysmography
8.  An effective oral vitamin D replacement therapy in persons with spinal cord injury 
Background/objective
Vitamin D deficiency is prevalent in chronic spinal cord injury (SCI). A 3-month course of oral vitamin D3 to ‘normalize’ serum vitamin D levels was investigated.
Design
Prospective drug-intervention study.
Setting
VA Medical Center; private rehabilitation facility.
Methods
Seven individuals with chronic SCI and vitamin D deficiency completed 3 months of oral vitamin D3 (i.e. cholecalciferol) supplementation. At screening, baseline, and months 1 and 3, blood was collected for serum calcium, 25 hydroxyvitamin D [25(OH)D], intact parathyroid hormone (iPTH), and N-telopeptide (NTx); 24-hour urine for calcium, creatinine, and NTx was performed. Oral vitamin D3 (2000 IU daily) and elemental calcium (1.3 g daily) were prescribed for 90 days. The results are expressed as mean ± standard deviation (SD). Analysis of variance with a Fisher's post-hoc analysis was performed to test for differences between study visits. Subjects were classified as deficient (<20 ng/ml), relatively deficient (20–30 ng/ml), or not deficient (>30 ng/ml) in 25(OH)D.
Results
Serum 25(OH)D levels were greater at months 1 and 3 than at baseline (26 ± 6 and 48 ± 17 vs. 14 ± 2 ng/ml; P = 0.005). Six of seven subjects were no longer deficient [25(OH)D >30 ng/ml] by month 3. Serum iPTH levels were significantly decreased at month 1 and month 3; serum NTx levels were significantly lower at month 3 than at baseline. Serum and urinary calcium levels remained within the normal range.
Conclusion
A daily prescription of 2000 IU of oral vitamin D3 for 3 months safely raised serum 25(OH)D levels into the normal range in persons with chronic SCI on calcium supplementation.
doi:10.1179/2045772311Y.0000000032
PMCID: PMC3184482  PMID: 22118252
Vitamin D deficiency; Nutritional supplementation; Calcium; Vitamin D; Osteoporosis; Spinal cord injuries; Bone loss; Cholecalciferol; Paraplegia; Tetraplegia; Veterans
9.  31st G. Heiner Sell Lectureship: Secondary Medical Consequences of Spinal Cord Injury 
Persons with spinal cord injury (SCI) have secondary medical consequences of paralysis and/or the consequences of extreme inactivity. The metabolic changes that result from reduced activity include insulin resistance with carbohydrate disorders and dyslipidemia. A higher prevalence of coronary artery calcification was found in persons with SCI than that in matched able-bodied controls. A depression in anabolic hormones, circulating testosterone and growth hormone, has been described. Adverse soft tissue body composition changes of increased adiposity and reduced skeletal muscle are appreciated. Immobilization is the cause for sublesional disuse osteoporosis with an associated increased risk of fragility fracture. Bowel dysmotility affects all segments of the gastrointestinal tract, with an interest in better defining and addressing gastroesophageal reflux disease and difficulty with evacuation. Developing and testing more effective approaches to cleanse the bowel for elective colonoscopy are being evaluated. The extent of respiratory dysfunction depends on the level and completeness of SCI. Individuals with higher spinal lesions have both restrictive and obstructive airway disease. Pharmacological approaches and expiratory muscle training are being studied as interventions to improve pulmonary function and cough strength with the objective of reducing pulmonary complications. Persons with spinal lesions above the 6th thoracic level lack both cardiac and peripheral vascular mechanisms to maintain blood pressure, and they are frequently hypotensive, with even worse hypotension with upright posture. Persistent and/or orthostatic hypotension may predispose those with SCI to cognitive impairments. The safety and efficacy of anti-hypotensive agents to normalize blood pressure in persons with higher level cord lesions is being investigated.
doi:10.1310/sci1804-354
PMCID: PMC3584784  PMID: 23459498
airway disease; anabolic hormones; cardiovascular risk; constipation; hypotension; insulin resistance; osteoporosis
10.  Transmission of low-intensity vibration through the axial skeleton of persons with spinal cord injury as a potential intervention for preservation of bone quantity and quality 
Background/objective
Persons with spinal cord injury (SCI) develop marked bone loss from paralysis and immobilization. Low-intensity vibration (LIV) has shown to be associated with improvement in bone mineral density in post-menopausal women and children with cerebral palsy. We investigated the transmissibility of LIV through the axial skeleton of persons with SCI as an initial approach to determine whether LIV may be used as a clinical modality to preserve skeletal integrity.
Methods
Transmission of a plantar-based LIV signal (0.27 ± 0.11 g; 34 Hz) from the feet through the axial skeleton was evaluated as a function of tilt-table angle (15, 30, and 45°) in seven non-ambulatory subjects with SCI and ten able-bodied controls. Three SCI and five control subjects were also tested at 0.44 ± 0.18 g and 34 Hz. Transmission was measured using accelerometers affixed to a bite-bar to determine the percentage of LIV signal transmitted through the body.
Results
The SCI group transmitted 25, 34, and 43% of the LIV signal, and the control group transmitted 28, 45, and 57% to the cranium at tilt angles of 15, 30, and 45°, respectively. No significant differences were noted between groups at any of the three angles of tilt.
Conclusion
SCI and control groups demonstrated equivalent transmission of LIV, with greater signal transmission observed at steeper angles of tilt. This work supports the possibility of the utility of LIV as a means to deliver mechanical signals in a form of therapeutic intervention to prevent/reverse skeletal fragility in the SCI population.
doi:10.1179/107902610x12886261091758
PMCID: PMC3066482  PMID: 21528627
Vibration; Osteoporosis; Spinal cord injuries; Immobilization; Paralysis; Bone loss; Tetraplegia; Paraplegia
11.  Cognitive Profile of Chronic Kidney Disease and Hemodialysis Patients without Dementia 
Nephron. Clinical Practice  2010;116(3):c247-c255.
Background/Aims
The high risk and prevalence of dementia among patients with chronic kidney disease (CKD) and in those receiving hemodialysis (HD) may be preceded by mild cognitive impairment (MCI). We aimed to assess cognitive function in CKD and HD patients with no history of stroke or dementia, in order to identify and characterize early cognitive deficits.
Methods
24 CKD and 27 HD male outpatients without history of cerebrovascular or neurodegenerative disease underwent comprehensive neuropsychological testing in an observational cross-sectional study. Test results were used to categorize patients into MCI subtypes.
Results
All subjects scored ≥28 on the Mini-Mental State Examination. The prevalence of executive function was at least 25% in both groups and memory impairment occurred in 13% of the HD patients and 15% of those with CKD. MCI occurred in 76% of the group and HD patients showed a higher prevalence of MCI compared to CKD patients (89 vs. 63%) with a preponderance (>70%) of cases across both groups classified as non-amnestic MCI.
Conclusion
Predialysis CKD and HD patients have a high prevalence of MCI despite normal global cognitive function. MCI was more prevalent among the HD patients and deficits more frequently resulted in non-amnestic MCI.
doi:10.1159/000317206
PMCID: PMC2945277  PMID: 20606486
Cognition; Mild cognitive impairment; Cerebrovascular disease; Chronic kidney disease; Hemodialysis
12.  Underestimation of Bone Loss of the Spine With Posterior-Anterior Dual-Energy X-Ray Absorptiometry in Patients With Spinal Cord Injury 
Background:
Bone mineral density (BMD) of the lumbar spine (L-spine) has been reported to be normal by routine posterior-anterior (PA) bone density imaging in patients with chronic spinal cord injury (SCI).
Objective:
To determine BMD of the L-spine by PA and lateral (LAT) dual-energy radiographic absorptiometry (DXA) in patients with chronic SCI.
Design:
Prospective study.
Setting:
Veterans Affairs Medical Center and a private rehabilitation facility.
Methods:
Measurements of the PA and LAT L-spine and hip were performed in 15 patients with SCI: 9 with tetraplegia and 6 with paraplegia. The DXA (GE Lunar Advance DXA) images were obtained using standard software. Results are reported as mean ± SD.
Results:
The mean age was 35 ± 15 years (range  =  20–62 years), and the duration of injury was 57 ± 74 months (range  =  3–240 months). T- and Z-scores were lower for the LAT L-spine than those for PA L-spine (T-scores L2: −0.7 ± 1.2 vs 0.0 ± 1.4, P < 0.01; L3: −0.9 ± 1.6 vs 0.3 ± 1.3, P < 0.002; L2-L3: −0.8 ± 1.3 vs 0.2 ± 1.3, P < 0.001; Z-scores L2: −0.3 ± 1.1 vs 0.2 ± 1.2, P < 0.05; L3: −0.6 ± 1.3 vs 0.5 ± 1.3, P < 0.01; L2-L3: −0.4 ± 1.1 vs 0.4 ± 1.2, P < 0.005). The T- and Z-scores for the total hip (−1.1 ± 1.0 and −1.0 ± 1.0, respectively) and L2-L3 LAT L-spine demonstrated remarkable similarity, whereas the L2-L3 PA L-spine scores were not reduced. Bone mineral density of the LAT L-spine, but not the PA L-spine, was significantly reduced with increasing duration of injury.
Conclusions:
Individuals with SCI may have bone loss of the L-spine that is evident on LAT DXA that may be misdiagnosed by PA DXA, underestimating the potential risk of fracture.
PMCID: PMC2920114  PMID: 20737794
Spinal cord injuries; Paraplegia; Tetraplegia; Bone mineral density; Vertebral body; Dual-energy X-ray absorptiometry; Osteoporosis
13.  Effects of Acute Nitric Oxide Synthase Inhibition on Lower Leg Vascular Function in Chronic Tetraplegia 
Background/Objective:
To improve our understanding of the lower-leg vascular responses of nitric oxide synthase inhibition in persons with tetraplegia.
Participants:
Six people with chronic tetraplegia and 6 age-matched controls.
Methods:
Lower-leg relative vascular resistance and venous volume variation were obtained by venous occlusion plethysmography and blood pressure by auscultation at baseline. Postintravenous infusion of the nitric oxide synthase inhibitor NG-nitro-l-arginine-methyl-ester (1 mg·kg−1) or placebo on separate days.
Results:
At baseline in the group with tetraplegia compared with controls, mean arterial pressure and relative vascular resistance of the leg were significantly lower. After nitric oxide synthase inhibition, mean arterial pressure and lower leg vascular resistance were significantly elevated in both groups. There were no group or intervention differences in venous volume variation.
Conclusion:
These preliminary results suggest that nitric oxide synthase inhibition with 1 mg·kg−1 NG-nitro-l-arginine-methyl-ester normalizes seated blood pressure and lower leg vascular resistance to control group baseline levels.
PMCID: PMC2792459  PMID: 20025149
Spinal cord injuries; l-NAME; Nitric oxide synthase; Tetraplegia; Vascular resistance; Vasoregulation
14.  Acute Suppression of Bone Turnover With Calcium Infusion in Persons With Spinal Cord Injury 
Background:
Some people with chronic spinal cord injury (SCI) have low vitamin D levels and secondary hyperparathyroidism.
Objective:
To determine whether, and to what extent, an acute calcium infusion decreased levels of N-telopeptide (NTx), a marker of osteoclastic activity, in individuals with chronic SCI.
Study Design:
Case series.
Subjects:
Eight men with chronic SCI. A relatively low serum 25 hydroxyvitamin D concentration (25[OH]D ≤20 ng/mL) and/or a high parathyroid hormone (PTH) (>55 pg/mL) was a prerequisite for study inclusion.
Methods:
Calcium gluconate bolus 0.025 mmol elemental calcium/kg over 20 minutes followed by a constant infusion of 0.025 mmol/kg per hour for 6 hours was infused; blood samples were collected every 2 hours for measurement of serum total calcium, creatinine, NTx, and PTH.
Results:
All results are expressed as means (± SDs). Baseline serum 25-hydroxyvitamin D level was 14.5 ± 3.5 ng/mL (range: 10.2–19.6 ng/mL); PTH, 70 ± 25 pg/mL (range: 37–100 pg/mL); and NTx, 21 ± 7 nM bone collagen equivalents (BCE) (range: 14–34 nM). At 2, 4, and 6 hours after the calcium infusion, serum calcium rose from 9.3 ± 0.2 to 10.8 ± 0.9, 10.5 ± 0.8, and 10.6 ± 0.6 mg/d; PTH was suppressed from 70 ± 25 pg/mL to 18 ± 12, 16 ± 9, and 15 ± 9 pg/mL, respectively; NTx fell from 21 ± 8 nM BCE to 17 ± 5, 12 ± 4, and 12 ± 3 nM BCE, respectively.
Conclusions:
Serum NTx is a marker for bone collagen catabolism, and its reduction suggests that bone turnover was decreased. A relative deficiency of vitamin D associated with chronically elevated levels of PTH would be expected to increase bone turnover and to worsen the bone loss associated with immobilization.
PMCID: PMC2830678  PMID: 19777860
Immobilization; Tetraplegia; Paraplegia; Vitamin D; Calcium; Parathyroid hormone; N-telopeptide; Bone resorption; Osteoporosis
15.  Provocative Stimulation of Growth Hormone: A Monozygotic Twin Study Discordant for Spinal Cord Injury 
Background/Objective:
A blunted growth hormone (GH) response to provocative testing and/or low levels of plasma insulin-like growth factor-I (IGF-I) have been reported in persons with spinal cord injury (SCI). A reduction in activity of the GH–IGF-I axis may have deleterious effects on body composition and function. Provocative testing for GH stimulation was performed to determine the response in monozygotic twins that were discordant for SCI.
Methods:
GH stimulation testing was performed by the administration of intravenous arginine.
Results:
Nine SCI twins with paraplegia, a mean age of 39 ± 9 years, and duration of injury of 14 ± 9 years were studied. The twins with SCI had a significantly lower body mass index than non-SCI twins (22.5 ± 4.0 vs 25.1 ± 4.2 kg/m2; P < 0.05); percent fat mass was greater in the twins with SCI (30 ± 11% vs 22 ± 10%; P < 0.05). Baseline serum GH was correlated with percent fat only in the SCI twins. The response to GH provocative stimulation was less in the twins with SCI: peak GH response was 5.8 ± 6.6 vs 13.0 ± 7.3 ng/mL (P < 0.05), and sum GH response was 15.7 ± 15.6 vs 30.2 ± 17.3 ng/mL (P = 0.06). Although baseline serum GH was correlated with stimulated response in the SCI twins, this relationship was not found in the non-SCI twins. Adiposity was positively related to the provocative serum GH response in twins with SCI rather than negatively related, as noted in the non-SCI twins.
Conclusions:
This study confirms and extends prior work that reported a reduction in stimulated GH release in persons with SCI, which was related to baseline values.
PMCID: PMC2141728  PMID: 18092562
Spinal cord injuries; Growth hormone; Insulin-like growth factor-I; Paraplegia; Arginine stimulation test; Monozygotic twins
16.  Normalization of Supine Blood Pressure After Nitric Oxide Synthase Inhibition in Persons With Tetraplegia 
Background/Objective:
Orthostatic hypotension is a well-defined clinical consequence of spinal cord injury (SCI), particularly in those with tetraplegia. The etiology of orthostatic hypotension is thought to be loss of sympathetic vasomotor control, although other factors may play a role. There is evidence of up-regulation of nitric oxide synthase (NOS) activity after hind-limb suspension in rats, a condition of antigravity that may have similar vascular effects as shown in persons with tetraplegia caused by paralysis. The study objective was to determine the effect of a NOS inhibitor (nitro-L-arginine methyl ester [L-NAME]) on supine mean arterial pressure in persons with chronic tetraplegia compared with non-SCI controls.
Methods:
Fourteen individuals participated (7 with tetraplegia and 7 controls). Subjects visited the laboratory twice for placebo on day 1 and L-NAME (1 mg/kg) on day 2; both were infused intravenously over 60 minutes. Blood pressure was monitored for 3 hours after infusion at the brachial artery using a standard manual cuff.
Results:
Mean arterial pressure (MAP) was lower at baseline (P < 0.05) and after placebo administration (P < 0.0001) in the tetraplegia group compared with the control group. L-NAME increased MAP in both groups; however, the relative increase was greater in the tetraplegia group compared with the control group, such that group differences for MAP were eliminated. Supine MAP was normalized with L-NAME, and there was an increased sensitivity to NOS inhibition in the group with tetraplegia.
Conclusions:
These findings indicate that blood pressure dysregulation in persons with tetraplegia may reflect increased vascular NO and suggest a novel treatment of hypotension using NOS inhibition in this population.
PMCID: PMC2032001  PMID: 17385265
Spinal cord injuries; Arterial pressure; Orthostatic hypotension; Nitro-l-arginine methyl ester; Nitric oxide inhibitor; Tetraplegia
17.  Toward a VA Women's Health Research Agenda: Setting Evidence-based Priorities to Improve the Health and Health Care of Women Veterans 
Journal of General Internal Medicine  2006;21(Suppl 3):S93-S101.
The expansion of women in the military is reshaping the veteran population, with women now constituting the fastest growing segment of eligible VA health care users. In recognition of the changing demographics and special health care needs of women, the VA Office of Research & Development recently sponsored the first national VA Women's Health Research Agenda-setting conference to map research priorities to the needs of women veterans and position VA as a national leader in Women's Health Research. This paper summarizes the process and outcomes of this effort, outlining VA's research priorities for biomedical, clinical, rehabilitation, and health services research.
doi:10.1111/j.1525-1497.2006.00381.x
PMCID: PMC1513170  PMID: 16637953
women's health; research and development; research priorities; veterans; health care quality; access and evaluation

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