Testicular responses to hCG stimulation at varying doses in men with spinal cord injury.

STUDY DESIGN: Prospective. OBJECTIVES: To test whether provocative stimulation of the testes identifies men with chronic spinal cord injury (SCI), a population in which serum testosterone concentrations are often depressed, possibly due to gonadal dysfunction. To accomplish this objective, conventional and lower than the conventional doses of human chorionic gonadotropin (hCG) were administered. METHODS: Thirty men with chronic SCI (duration of injury >1 year; 18 and 65 years old; 16 eugonadal (>12.1 nmol l-1) and 14 hypogonadal (⩽12.1 nmol l-1)) or able-bodied (AB) men (11 eugonadal and 27 hypogonadal) were recruited for the study. Stimulation tests were performed to quantify testicular responses to the intramuscular administration of hCG at three dose concentrations (ithat is, 400, 2000 and 4000 IU). The hCG was administered on two consecutive days, and blood was collected for serum testosterone in the early morning prior to each of the two injections; subjects returned on day 3 for a final blood sample collection. RESULTS: The average gonadal response in the SCI and AB groups to each dose of hCG was not significantly different in the hypogonadal or eugonadal subjects, with the mean serum testosterone concentrations in all groups demonstrating an adequate response. CONCLUSIONS: This work confirmed the absence of primary testicular dysfunction without additional benefit demonstrated of provocative stimulation of the testes with lower than conventional doses of hCG. Our findings support prior work that suggested a secondary testicular dysfunction that occurs in a majority of those with SCI and depressed serum testosterone concentrations.

Bone loss at the distal femur and proximal tibia in persons with spinal cord injury: imaging approaches, risk of fracture, and potential treatment options.

Persons with spinal cord injury (SCI) undergo immediate unloading of the skeleton and, as a result, have severe bone loss below the level of lesion associated with increased risk of long-bone fractures. The pattern of bone loss in individuals with SCI differs from other forms of secondary osteoporosis because the skeleton above the level of lesion remains unaffected, while marked bone loss occurs in the regions of neurological impairment. Striking demineralization of the trabecular epiphyses of the distal femur (supracondylar) and proximal tibia occurs, with the knee region being highly vulnerable to fracture because many accidents occur while sitting in a wheelchair, making the knee region the first point of contact to any applied force. To quantify bone mineral density (BMD) at the knee, dual energy x-ray absorptiometry (DXA) and/or computed tomography (CT) bone densitometry are routinely employed in the clinical and research settings. A detailed review of imaging methods to acquire and quantify BMD at the distal femur and proximal tibia has not been performed to date but, if available, would serve as a reference for clinicians and researchers. This article will discuss the risk of fracture at the knee in persons with SCI, imaging methods to acquire and quantify BMD at the distal femur and proximal tibia, and treatment options available for prophylaxis against or reversal of osteoporosis in individuals with SCI.

Provocative stimulation of the hypothalamic-pituitary-testicular axis in men with spinal cord injury.

STUDY DESIGN: Prospective study. OBJECTIVE: To determine the integrity of the hypothalamic-pituitary-testicular axis in healthy men with spinal cord injury (SCI). METHODS: Thirty healthy men with chronic SCI (37±10 years) and thirty-eight able-bodied (AB) controls (36±10 years) participated. Gonadotropin-releasing hormone (GnRH; 100 µg IV) was administered to determine gonadotropin release, and human chorionic gonadotropin (hCG; 4000 IU IM) was administered to determine testosterone (T) secretion. Responses to stimulation were categorized as 'responder' or 'non-responder' by clinical criteria. Single factor ANOVA with repeated measures was performed to identify group differences. RESULTS: The proportion of responders to pituitary GnRH stimulation was similar in the SCI group (22 subjects (73%) for the follicular-stimulating hormone (FSH) and 23 subjects (76%) for the luteinizing hormone (LH) to that of the AB group. The SCI-responder group had an increased FSH response after stimulation compared with the AB-responder group (P<0.05). The SCI-responder group had a greater LH area under the curve to GnRH stimulation than the AB-responder group (P=0.06). The peak FSH response was at 60 min and the peak LH response at 30 min, regardless of group designation. All groups had similar increases in serum T concentration to hCG stimulation. CONCLUSIONS: The pituitary response to stimulation in healthy men with SCI revealed an augmented FSH response; LH response only trended higher. The testicular response to provocative stimulation was similar in hypogonadal and eugondal subjects and in GnRH responders and non-responders. These findings suggest a lack of hypothalamic drive of pituitary gonadotropin release in healthy people with chronic SCI.

Greatly increased prevalence of esophageal dysmotility observed in persons with spinal cord injury.

The effects of spinal cord injury (SCI) on esophageal motility are largely unknown. Furthermore, due to the complete or partial loss of sensory innervation to the upper gastrointestinal tract, a symptom-based diagnosis of esophageal dysmotility is problematic in the SCI population. To determine the prevalence and characterize the type of motility disorders observed in persons with chronic SCI compared with that of able-bodied (AB) controls based on esophageal pressure topography isometrics acquired by high-resolution manometry and categorized by application of the Chicago Classification. High-resolution manometry of the esophagus was performed in 39 individuals: 14 AB, 12 with paraplegia (level of injury between T4-T12) and 13 with tetraplegia (level of injury between C5-C7). A catheter containing multiple pressure sensors arranged at 360° was introduced into the esophagi of subjects at a distance that allowed visualization of both the upper esophageal sphincters (UES) and lower esophageal sphincters (LES). After a period to acquire pressures at baseline, subjects were asked to perform 10 wet swallows with 5-mL boluses of isotonic saline while esophageal pressure and impedance were being recorded. No significant differences were noted for gender, age, or body mass index between AB and SCI groups. Twenty-one of 25 (84%) subjects with SCI had at least one motility abnormality: 12% with Type II achalasia, 4% with Type III achalasia, 20% with esophagogastric junction outflow obstruction, 4% with the hypercontractile esophagus, and 48% with peristaltic abnormalities (weak peristalsis with small or large defects or frequent failed peristalsis). In contrast, only 7% (1 out of 14) of the AB subjects had any type of esophageal motility disorder. Despite the lack of subjective complaints and clinical awareness, esophageal dysmotility appears to be a highly prevalent condition in persons with SCI. The use of new and improved techniques, as well as a more stringent classification system, permitted the identification of the presence of nonspecific motility disorders in almost all SCI subjects, including four individuals who were previously undiagnosed with achalasia. Future work in persons with SCI is required to clarify the clinical impact of this observation and to study potential associations between esophageal dysmotility, gastroesophageal reflux disease, and pulmonary function. An increased awareness of esophageal dysfunction in the SCI population may lead to the development of new clinical guidelines for the diagnosis, prevention, and treatment of these largely unrecognized disorders.

Acute nitric oxide synthase inhibition and cardiac conduction in persons with spinal cord injury: a short report.

NG-nitro L-arginine methyl ester (L-NAME) is a potent and non-specific inhibitor of nitric oxide synthase (NOS). NOS inhibition with L-NAME has been shown to adversely prolong electrocardiogram (ECG) intervals in an animal model, an observation which has yet to be evaluated in humans. We determined the effects of several weight-based L-NAME doses on ECG intervals in persons with tetraplegia and a neurologically-intact control group. This two-part investigation determined the effects of different weight-based doses of L-NAME in the supine (Study 1) and orthostatic position (Study 2). Subjects completed an open-label trial with intravenous administration of L-NAME at specific doses [i.e., 0, 1, 2 or 4 mg.kg-1] in the supine position. The SCI group completed an orthostatic challenge with or without il-NAME [i.e., 0, 1 or 2 mg.kg-'] and controls completed only a single visit [0 mg.kg-1]. Digital ECGs were obtained at baseline (BL), after infusion (60 minutes) and 1 hour post-infusion (120 minutes) in Study 1, and at BL, 60 minutes and at two, 10 minute post-infusion time points after head up tilt (Post-Tilt 1 and 2) in Study 2. Heart rate, PQ, QT, and heart rate corrected QT (QTC) intervals were determined. The groups were matched for demographics. Seven subjects with tetraplegia and 6 controls participated in Study 1; 7 subjects with tetraplegia and 7 controls participated in Study 2. No statistical differences were noted between or within groups at baseline on each study visit for the ECG variables. L-NAME, regardless of dose, did not significantly change any ECG interval. NOS inhibition with L-NAME, at the weight-based doses tested do not induce hypertensive crises and, did not adversely affect any ECG interval in persons with SCI or neurologically intact control subjects during supine rest or orthostatic provocation.

A small-scale clinical trial to determine the safety and efficacy of testosterone replacement therapy in hypogonadal men with spinal cord injury.

Men with spinal cord injury are at an increased risk for secondary medical conditions, including metabolic disorders, accelerated musculoskeletal atrophy, and, for some, hypogonadism, a deficiency, which may further adversely affect metabolism and body composition. A prospective, open label, controlled drug intervention trial was performed to determine whether 12 months of testosterone replacement therapy increases lean tissue mass and resting energy expenditure in hypogonadal males with spinal cord injury. Healthy eugonadal (n = 11) and hypogonadal (n = 11) outpatients with chronic spinal cord injury were enrolled. Hypogonadal subjects received transdermal testosterone (5 or 10 mg) daily for 12 months. Measurements of body composition and resting energy expenditure were obtained at baseline and 12 months. The testosterone replacement therapy group increased lean tissue mass for total body (49.6 ± 7.6 vs. 53.1 ± 6.9 kg; p < 0.0005), trunk (24.1 ± 4.1 vs. 25.8 ± 3.8 kg; p < 0.005), leg (14.5 ± 2.7 vs. 15.8 ±2.6 kg; p = 0.005), and arm (7.6 ± 2.3 vs. 8.0 ± 2.2 kg; p < 0.005) from baseline to month 12. After testosterone replacement therapy, resting energy expenditure (1328 ± 262 vs. 1440 ± 262 kcal/d; p < 0.01) and percent predicted basal energy expenditure (73 ± 9 vs. 79 ± 10%; p < 0.05) were significantly increased. In conclusion, testosterone replacement therapy significantly improved lean tissue mass and energy expenditure in hypogonadal men with spinal cord injury, findings that would be expected to influence the practice of clinical care, if confirmed. Larger, randomized, controlled clinical trials should be performed to confirm and extend our preliminary findings.

Intra-inter visit reproducibility of short-term linear and nonlinear measurement of heart rate variability in tetraplegia and neurologically intact controls.

Heart rate variability (HRV) from the frequency domain and three calculations of entropy (En), approximate (ApEn), sample (SampEn) and Lempel-Ziv (LZEn), were assessed for intra- and inter-visit reproducibility from short-term recordings in persons with tetraplegia and neurologically intact controls. The intraclass correlation coefficient (ICC) was calculated for multiple comparisons to determine the reproducibility in both groups during a 4 h visit and across three visits. By ICC in both groups, ApEn, SampEn and LZEn possessed excellent intra- (>or=0.87) and inter-visit reproducibility (>or=0.90). In contrast, frequency domain measures were collectively less concise. In general on intra- and inter-visit comparisons for both groups, high frequency (HF) measures were more reliable than low frequency (LF). In control subjects relative to other units of expression, normalized units (nu) of LF had the best intra-visit reliability across all comparisons. This was not the case on inter-visit comparisons where absolute (>or=0.74) and natural log (ln) (>or=0.66) representations of LF were more reliable. In the group with tetraplegia, LFln was the most reliable for comparisons up to or including 180 min (>or=0.60) and two visits (>or=0.63). Thus, calculations of En and HF HRV appear to be more reliable than LF HRV and less confounded by small sample sizes.