RESUMO
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.
Assuntos
Fêmur/fisiopatologia , Osteoporose/etiologia , Traumatismos da Medula Espinal/complicações , Tíbia/fisiopatologia , Absorciometria de Fóton/métodos , Densidade Óssea/fisiologia , Fêmur/diagnóstico por imagem , Humanos , Osteoporose/diagnóstico por imagem , Osteoporose/fisiopatologia , Medição de Risco/métodos , Traumatismos da Medula Espinal/fisiopatologia , Tíbia/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodosRESUMO
OBJECTIVE: The objective of this study was to develop the International Spinal Cord Injury (SCI) Endocrine and Metabolic Extended Data Set (ISCIEMEDS) within the framework of the International SCI Data Sets that would facilitate consistent collection and reporting of endocrine and metabolic findings in the SCI population. SETTING: This study was conducted in an international setting. METHODS: The ISCIEMEDS was developed by a working group. The initial ISCIEMEDS was revised based on suggestions from members of the International SCI Data Sets Committee, the International Spinal Cord Society (ISCoS) Executive and Scientific Committees, American Spinal Injury Association (ASIA) Board, other interested organizations, societies and individual reviewers. The data set was posted for two months on ISCoS and ASIA websites for comments. Variable names were standardized, and a suggested database structure for the ISCIEMEDS was provided by the Common Data Elements (CDEs) project at the National Institute on Neurological Disorders and Stroke (NINDS) of the US National Institute of Health (NIH), and are available at https://commondataelements.ninds.nih.gov/SCI.aspx#tab=Data_Standards. RESULTS: The final ISCIEMEDS contains questions on the endocrine and metabolic conditions related to SCI. Because the information may be collected at any time, the date of data collection is important to determine the time after SCI. ISCIEMEDS includes information on carbohydrate metabolism (6 variables), calcium and bone metabolism (12 variables), thyroid function (9 variables), adrenal function (2 variables), gonadal function (7 variables), pituitary function (6 variables), sympathetic nervous system function (1 variable) and renin-aldosterone axis function (2 variables). CONCLUSION: The complete instructions for data collection and the data sheet itself are freely available on the website of ISCoS (http://www.iscos.org.uk/international-sci-data-sets).
Assuntos
Doenças Metabólicas/metabolismo , Traumatismos da Medula Espinal/metabolismo , Adolescente , Adulto , Idoso , Elementos de Dados Comuns , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Humanos , Cooperação Internacional , Masculino , Doenças Metabólicas/terapia , Pessoa de Meia-Idade , National Institute of Neurological Disorders and Stroke (USA) , Traumatismos da Medula Espinal/terapia , Estados Unidos , Adulto JovemRESUMO
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.
Assuntos
Gonadotropina Coriônica/administração & dosagem , Hipogonadismo/diagnóstico , Traumatismos da Medula Espinal/complicações , Testículo/efeitos dos fármacos , Adolescente , Adulto , Idoso , Relação Dose-Resposta a Droga , Humanos , Hipogonadismo/etiologia , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Traumatismos da Medula Espinal/sangue , Testosterona/sangue , Adulto JovemRESUMO
Bone loss after spinal cord injury (SCI) is rapid, severe, and refractory to interventions studied to date. Mice with sclerostin gene deletion are resistant to the severe sublesional bone loss induced by SCI, further indicating pharmacological inhibition of sclerostin may represent a promising novel approach to this challenging medical problem. INTRODUCTION: The bone loss secondary to spinal cord injury (SCI) is associated with several unique pathological features, including the permanent immobilization, neurological dysfunction, and systemic hormonal alternations. It remains unclear how these complex pathophysiological changes are linked to molecular alterations that influence bone metabolism in SCI. Sclerostin is a key negative regulator of bone formation and bone mass. We hypothesized that sclerostin could function as a major mediator of bone loss following SCI. METHODS: To test this hypothesis, 10-week-old female sclerostin knockout (SOST KO) and wild type (WT) mice underwent complete spinal cord transection or laminectomy (Sham). RESULTS: At 8 weeks after SCI, substantial loss of bone mineral density was observed at the distal femur and proximal tibia in WT mice but not in SOST KO mice. By µCT, trabecular bone volume of the distal femur was markedly decreased by 64 % in WT mice after SCI. In striking contrast, there was no significant reduction of bone volume in SOST KO/SCI mice compared with SOST KO/sham. Histomorphometric analysis of trabecular bone revealed that the significant reduction in bone formation rate following SCI was observed in WT mice but not in SOST KO mice. Moreover, SCI did not alter osteoblastogenesis of marrow stromal cells in SOST KO mice. CONCLUSION: Our findings demonstrate that SOST KO mice were protected from the major sublesional bone loss that invariably follows SCI. The evidence indicates that sclerostin is an important mediator of the marked sublesional bone loss after SCI, and that pharmacological inhibition of sclerostin may represent a promising novel approach to this challenging clinical problem.
Assuntos
Densidade Óssea , Reabsorção Óssea/etiologia , Deleção de Genes , Glicoproteínas/genética , Traumatismos da Medula Espinal/complicações , Proteínas Adaptadoras de Transdução de Sinal , Animais , Reabsorção Óssea/genética , Feminino , Peptídeos e Proteínas de Sinalização Intercelular , Camundongos , Camundongos KnockoutRESUMO
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.
Assuntos
Gonadotropina Coriônica/administração & dosagem , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Luteinizante/sangue , Traumatismos da Medula Espinal/sangue , Testosterona/sangue , Administração Intravenosa , Adulto , Análise de Variância , Relação Dose-Resposta a Droga , Humanos , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Traumatismos da Medula Espinal/fisiopatologia , Fatores de TempoRESUMO
STUDY DESIGN: Descriptive study. OBJECTIVES: The goal of this study was to determine the effects of spinal cord injury (SCI) on aspects of the focal adhesion kinase (FAK) signaling pathway 56 days post injury in rat gastrocnemius. SETTING: This study was conducted in Bronx, NY, USA. METHODS: Three-month-old male Wistar rats were exposed to either a sham surgery (n=10) or complete T4 spinal cord transection (n=10). Rats were killed 56 days following surgery and the muscle was collected. Following homogenization, proteins of the FAK pathway were analyzed by western immunoblotting or reverse transcription-qPCR. In addition, cellular markers for proteins that target the degradation of FAK were investigated. RESULTS: SCI resulted in significantly lower levels of total and phosphorylated FAK, cSrc and p70S6k, and a trend for increased FRNK protein expression. SCI did not change levels of the α7 or ß1 integrin subunits, total or phosphorylated ERK1/2, phosphorylated Akt and TSC2 or total p70S6k. SCI resulted in a greater expression of total Akt. mRNA expression of FAK and the α7 or ß1 integrins remained unchanged between sham and SCI groups. Caspase-3/7 activity and Trim72 mRNA and protein expression remained unchanged following SCI. CONCLUSION: SCI results in diminished FAK signaling and is independent of ERK1/2 and Akt. SCI has no effect on mRNA levels for genes encoding components of the focal adhesion 56 days after injury.
Assuntos
Quinase 1 de Adesão Focal/metabolismo , Músculo Esquelético/enzimologia , Transdução de Sinais/fisiologia , Traumatismos da Medula Espinal/patologia , Animais , Caspases/metabolismo , Modelos Animais de Doenças , Quinase 1 de Adesão Focal/genética , Regulação da Expressão Gênica/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Proteína Oncogênica v-akt/metabolismo , Fosforilação , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Traumatismos da Medula Espinal/metabolismoRESUMO
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.
Assuntos
Transtornos da Motilidade Esofágica/epidemiologia , Traumatismos da Medula Espinal/complicações , Idoso , Impedância Elétrica , Transtornos da Motilidade Esofágica/diagnóstico , Transtornos da Motilidade Esofágica/etiologia , Esfíncter Esofágico Inferior/fisiopatologia , Esfíncter Esofágico Superior/fisiopatologia , Humanos , Manometria/métodos , Pessoa de Meia-Idade , Peristaltismo/fisiologia , Pressão , PrevalênciaRESUMO
UNLABELLED: Spinal cord injury (SCI) causes rapid and marked bone loss. The present study demonstrates that low-intensity vibration (LIV) improves selected biomarkers of bone turnover and gene expression and reduces osteoclastogenesis, suggesting that LIV may be expected to benefit to bone mass, resorption, and formation after SCI. INTRODUCTION: Sublesional bone is rapidly and extensively lost following spinal cord injury (SCI). Low-intensity vibration (LIV) has been suggested to reduce loss of bone in children with disabilities and osteoporotic women, but its efficacy in SCI-related bone loss has not been tested. The purpose of this study was to characterize effects of LIV on bone and bone cells in an animal model of SCI. METHODS: The effects of LIV initiated 28 days after SCI and provided for 15 min twice daily 5 days each week for 35 days were examined in female rats with moderate severity contusion injury of the mid-thoracic spinal cord. RESULTS: Bone mineral density (BMD) of the distal femur and proximal tibia declined by 5 % and was not altered by LIV. Serum osteocalcin was reduced after SCI by 20 % and was increased by LIV to a level similar to that of control animals. The osteoclastogenic potential of bone marrow precursors was increased after SCI by twofold and associated with 30 % elevation in serum CTX. LIV reduced the osteoclastogenic potential of marrow precursors by 70 % but did not alter serum CTX. LIV completely reversed the twofold elevation in messenger RNA (mRNA) levels for SOST and the 40 % reduction in Runx2 mRNA in bone marrow stromal cells resulting from SCI. CONCLUSION: The findings demonstrate an ability of LIV to improve selected biomarkers of bone turnover and gene expression and to reduce osteoclastogenesis. The study indicates a possibility that LIV initiated earlier after SCI and/or continued for a longer duration would increase bone mass.
Assuntos
Osteoporose/prevenção & controle , Traumatismos da Medula Espinal/complicações , Vibração/uso terapêutico , Absorciometria de Fóton/métodos , Animais , Biomarcadores/sangue , Densidade Óssea , Proteínas Morfogenéticas Ósseas/biossíntese , Proteínas Morfogenéticas Ósseas/genética , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/biossíntese , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Modelos Animais de Doenças , Feminino , Fêmur/fisiopatologia , Regulação da Expressão Gênica/fisiologia , Marcadores Genéticos/genética , Músculo Esquelético/patologia , Tamanho do Órgão , Osteocalcina/sangue , Osteoclastos/fisiologia , Osteoporose/etiologia , Osteoporose/metabolismo , RNA Mensageiro/genética , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/metabolismo , Tíbia/fisiopatologiaRESUMO
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.
Assuntos
Sistema de Condução Cardíaco/efeitos dos fármacos , Óxido Nítrico Sintase/antagonistas & inibidores , Traumatismos da Medula Espinal/enzimologia , Idoso , Pressão Arterial/efeitos dos fármacos , Estudos de Coortes , Tontura , Relação Dose-Resposta a Droga , Eletrocardiografia/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , NG-Nitroarginina Metil Éster/farmacologia , Estudos Prospectivos , Quadriplegia/enzimologia , Quadriplegia/fisiopatologia , Decúbito Dorsal , Adulto JovemRESUMO
STUDY DESIGN: Male rats with complete transections of the spinal cord were administered vehicle or methylprednisolone (MP) for 24 h, with or without infusion, for 7 days, of testosterone at either a replacement or low pharmacological doses. Muscles were collected at 7 days after SCI. OBJECTIVE: The objective of this study is to determine, in a rat model of complete spinal cord transection, whether testosterone reduces muscle atrophy or upregulates muscle atrophy-linked genes, induced by 24 h of MP administration at doses comparable to those prescribed in man during the period immediately following acute spinal cord injury (SCI) in an attempt to preserve neurological function. RESULTS: MP significantly reduced the mass of triceps, soleus and plantaris, and significantly increased expression of genes that promote atrophy. Testosterone significantly reduced muscle atrophy induced by MP, but did not prevent it; there was no difference between low- or high-dose testosterone in reducing MP-induced muscle loss. High-dose testosterone reduced expression of muscle atrophy genes more than did low dose. Testosterone-induced declines in mRNA levels for these atrophy-associated genes did not correlate well with protection against MP-induced muscle atrophy. CONCLUSIONS: MP induces marked and lasting changes in the biology of muscle that persisted for at least 7 days, or 6 days after MP has been eliminated from the body. Testosterone partially protected against muscle atrophy and gene expression changes caused by 1 day of MP.
Assuntos
Metilprednisolona/toxicidade , Atrofia Muscular Espinal/induzido quimicamente , Atrofia Muscular Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/tratamento farmacológico , Testosterona/farmacologia , Animais , Anti-Inflamatórios/toxicidade , Modelos Animais de Doenças , Masculino , Atrofia Muscular Espinal/prevenção & controle , Ratos , Ratos WistarRESUMO
STUDY DESIGN: Spinal cord injury (SCI) results in gastrointestinal (GI) complications, including gastroesophageal reflux disease and constipation, but much of the data is based on older technology. OBJECTIVE: GI transit times were determined in subjects with SCI using a new device called a SmartPill. Our principal goal was to assess whether this new technology can be applied in persons with SCI. METHODS: SCI and age- and gender-matched able-bodied (AB) control subjects not taking proton pump inhibitors were studied. Following an 8-h overnight fast, subjects consumed 120 g EggBeaters (60 kcal), two slices of white bread (120 kcal) and 30 g strawberry jam (74 kcal). A pH calibrated SmartPill capsule was swallowed with 8 ounces of water, after which subjects fasted for an additional 6 h prior to consuming an Ensure Plus nutrition shake (350 kcal). Subjects remained fasted for an additional 2 h, after which time they resumed their regular diets. RESULTS: Twenty subjects with SCI and 10 AB control subjects were studied. Data are expressed as mean±s.d. Comparing the group with SCI to the AB control group, gastric emptying time (GET), colonic transit time (CTT) and whole gut transit time (WGTT) were prolonged (GET: 10.6±7.2 vs 3.5±1.0 h, P<0.01; CTT: 52.3±42.9 vs 14.2±7.6 h, P=0.01; WGTT: 3.3±2.5 vs 1.0±0.7 days, P<0.01). No complications or side effects were reported. CONCLUSION: Our results indicate that the SmartPill technology is a safe, non-invasive assessment technique that provides valid diagnostic information in persons with SCI.
Assuntos
Endoscopia por Cápsula/instrumentação , Endoscopia por Cápsula/métodos , Gastroenteropatias/diagnóstico , Gastroenteropatias/fisiopatologia , Motilidade Gastrointestinal/fisiologia , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/fisiopatologia , Adulto , Idoso , Feminino , Esvaziamento Gástrico/fisiologia , Gastroenteropatias/etiologia , Trânsito Gastrointestinal/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Quadriplegia/diagnóstico , Quadriplegia/etiologia , Quadriplegia/fisiopatologia , Traumatismos da Medula Espinal/etiologia , Fatores de TempoRESUMO
BACKGROUND: The 1984/86 published neurogram results showing only rare sympathetic nerve activity (SNA) to the muscles and skin in tetraplegia are still accepted. The present study by a different method attempted to confirm or deny those findings. METHODS AND RESULTS: The effect of basal SNA to the microcirculation of the feet and calf in 10 complete (AIS A) traumatic tetraplegic and 10 healthy age matched subjects were evaluated by wavelet transform of laser Doppler flowmetry (LDF) recordings. The results clearly indicated there is significant basal SNA from the decentralized spinal cord in tetraplegia. In addition, wavelet analysis allowed a study of other influences on the microcirculation besides SNA. Collectively, in tetraplegia compared with controls, the powers of the low frequency oscillations in blood flow were reduced; in that the endothelium caused less vasodilatation while the SNA and intrinsic vascular smooth muscles induced smaller degrees of vasoconstriction. However, the high frequency and especially the cardiac powers were greater. The latter presenting an obvious important factor for the preservation of blood flow in the microcirculation. CONCLUSIONS: It is suggested that basal SNA to the cutaneous microcirculation occurs in complete tetraplegia, and the significant levels of circulating noradrenaline reported by others indicate this is also true in other parts of the body. This may explain the usual absence of severe, incapacitating, autonomic deficiency in this condition.
Assuntos
Fluxometria por Laser-Doppler , Microcirculação/fisiologia , Quadriplegia/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Análise de Ondaletas , Adulto , Pressão Sanguínea/fisiologia , Pé/irrigação sanguínea , Pé/fisiopatologia , Humanos , Perna (Membro)/irrigação sanguínea , Perna (Membro)/patologia , Perna (Membro)/fisiopatologia , Masculino , Pessoa de Meia-Idade , Quadriplegia/patologia , Fluxo Sanguíneo Regional/fisiologia , Coxa da Perna/patologia , Dedos do Pé/irrigação sanguínea , Dedos do Pé/fisiopatologia , Adulto JovemRESUMO
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.
Assuntos
Terapia de Reposição Hormonal/efeitos adversos , Hipogonadismo/complicações , Hipogonadismo/tratamento farmacológico , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/tratamento farmacológico , Testosterona/efeitos adversos , Testosterona/uso terapêutico , Adolescente , Adulto , Idoso , Composição Corporal , Exame Retal Digital , Metabolismo Energético , Humanos , Hipogonadismo/patologia , Hipogonadismo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To develop the International Spinal Cord Injury (SCI) Endocrine and Metabolic Function Basic Data Set within the framework of the International SCI Data Sets that would facilitate consistent collection and reporting of basic endocrine and metabolic findings in the SCI population. SETTING: International. METHODS: The International SCI Endocrine and Metabolic Function Data Set was developed by a working group. The initial data set document was revised on the basis of suggestions from members of the Executive Committee of the International SCI Standards and Data Sets, the International Spinal Cord Society (ISCoS) Executive and Scientific Committees, American Spinal Injury Association (ASIA) Board, other interested organizations and societies, and individual reviewers. In addition, the data set was posted for 2 months on ISCoS and ASIA websites for comments. RESULTS: The final International SCI Endocrine and Metabolic Function Data Set contains questions on the endocrine and metabolic conditions diagnosed before and after spinal cord lesion. If available, information collected before injury is to be obtained only once, whereas information after injury may be collected at any time. These data include information on diabetes mellitus, lipid disorders, osteoporosis, thyroid disease, adrenal disease, gonadal disease and pituitary disease. The question of gonadal status includes stage of sexual development and that for females also includes menopausal status. Data will be collected for body mass index and for the fasting serum lipid profile. The complete instructions for data collection and the data sheet itself are freely available on the websites of ISCoS (http://www.iscos.org.uk) and ASIA (http://www.asia-spinalinjury.org).
Assuntos
Doenças do Sistema Endócrino/metabolismo , Doenças do Sistema Endócrino/fisiopatologia , Doenças Metabólicas/metabolismo , Doenças Metabólicas/fisiopatologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Comorbidade/tendências , Bases de Dados como Assunto/organização & administração , Bases de Dados como Assunto/tendências , Doenças do Sistema Endócrino/epidemiologia , Feminino , Saúde Global/tendências , Humanos , Cooperação Internacional , Masculino , Doenças Metabólicas/epidemiologia , Traumatismos da Medula Espinal/epidemiologiaRESUMO
STUDY DESIGN: Review. OBJECTIVES: In subjects with spinal cord injury (SCI), there is strong evidence for platelet hyperactivity, which may stimulate atherosclerosis and coronary heart disease (CHD). The literature was reviewed. BACKGROUND: Individuals with SCI develop premature CHD. In addition to the conventional risk factors associated with CHD, there are pathologic hematological factors involved in atherogenesis that are similar to those that have been demonstrated in individuals with diabetes, and these hematological factors might affect individuals with SCI. One such hematological factor, platelet aggregation, is essential for the development of CHD, which results from thrombus formation in the coronary vasculature. Prostacyclin (PGI(2)) is a potent inhibitor of platelet aggregation and is thought to have a beneficial role in inhibiting atherogenesis; therefore, it is possible that individuals with SCI have impaired PGI(2) receptor function. METHODS: We reviewed the literature by conducting a search using PubMed (1970-2007). RESULTS: Acute thrombosis is emerging as an important factor in the etiology of CHD and therefore could mediate the risk of CHD in persons with SCI, in addition to previously known risk factors such as hyperlipidemia, hypertension, hyperlipidemia, diabetes mellitus and hyperinsulinemia. Because PGI(2) may retard atherogenesis through its inhibitory effects on platelet function, we discuss the effects of PGI(2) on platelets in persons with SCI in this review. CONCLUSIONS: Subjects with chronic SCI develop abnormal platelet function, resulting in the production of atherogenic and thrombogenic factors for the following reasons: (1) the PGI(2) and insulin receptors on their platelets are impaired; (2) thrombin generation and platelet-derived growth factor release are elevated; (3) insulin-induced nitric oxide production by platelets is markedly impaired; and (4) a circulating antibody (immunoglobulin G (IgG)) blocks the antithrombotic effect of both insulin and PGI(2) receptors. Thus, this IgG molecule is thought to be one of the pathological mediators of the increased incidence of CHD in individuals with SCI.
Assuntos
Doença das Coronárias/epidemiologia , Doença das Coronárias/etiologia , Hemostáticos/metabolismo , Traumatismos da Medula Espinal/epidemiologia , Plaquetas/metabolismo , Epoprostenol/metabolismo , Humanos , Insulina , Óxido Nítrico/metabolismo , Fator de Crescimento Derivado de Plaquetas/metabolismo , PubMed/estatística & dados numéricos , Fatores de Risco , Trombina/metabolismo , Fatores de Tempo , Trítio/metabolismoRESUMO
OBJECTIVE: Administration after spinal cord injury (SCI) of methylprednisolone (MP) for 24-48 h has been suggested to improve functional outcome. The safety of this approach has been questioned because of the known adverse effects of glucocorticoids on skeletal muscle and the immune system. The purpose of this study was to explicitly test adverse effects of regimen of MP administration on skeletal muscle. STUDY DESIGN: Male rats underwent spinal cord transection at T9-T10, followed by an intravenous injection of MP and subsequent infusion of MP for 24 h. RESULTS: MP significantly reduced the weight of the triceps, soleus, plantaris and gastrocnemius muscles, with the greatest effect being a 63% decrease in triceps weight (for example, muscle above the level of lesion) at 7 days; below the level of lesion, gastrocnemius weight was reduced by 33% by SCI alone, and by 45% by SCI and MP. Centralized nuclei were found in myofibers of the gastrocnemius and triceps from the MP-SCI group, but not other groups. MP increased expression in the triceps, soleus and plantaris of FOXO1, MAFbx, MuRF1 and REDD1 at 1 day, and, in plantaris, at 7 days. CONCLUSIONS: Thus, 1 day of MP at a dose comparable to those routinely employed in clinical practice immediately after SCI resulted in marked atrophy of functionally intact muscle above the level of lesion, and worsened atrophy of paralyzed muscle below the level of lesion, associated with elevations in expression of four genes involved in pathways associated with muscle atrophy.
Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Metilprednisolona/administração & dosagem , Músculo Esquelético/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Traumatismos da Medula Espinal , Análise de Variância , Animais , Modelos Animais de Doenças , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Masculino , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Músculo Esquelético/patologia , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Proteínas Ligases SKP Culina F-Box/genética , Proteínas Ligases SKP Culina F-Box/metabolismo , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Fatores de Tempo , Fatores de Transcrição , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
BACKGROUND: The outcome of colonoscopy is highly dependent upon the quality of bowel cleansing prior to the procedure. Oral sodium phosphate solutions (OSPS) or preparations containing polyethylene glycol (PEG) are generally employed. However, the safety of administering OSPS prior to colonoscopy has been questioned because of the potential for renal failure. AIM: To compare rates of renal failure after OSPS and PEG in a randomized, prospective trial and to assess the quality of colonoscopy after these two bowel preparations. METHODS: Subjects with eGFR >or= 60 ml/min/1.73 m(2) and expressed willingness to adhere to hydration recommendations were randomized to OSPS or PEG solutions. Renal function was assessed 1 week prior to, immediately prior to, and 1 week after colonoscopy. RESULTS: No subject had acute kidney failure after OSPS or PEG. OSPS was associated with significant increases in the serum phosphate and sodium levels and significant decreases in the calcium and potassium levels. These values returned to normal limits in all subjects by 1 week after colonoscopy. The quality of colonic cleansing was superior after OSPS than after PEG (Ottawa score 2.5 +/- 2.2 vs. 3.5 +/- 2.3, respectively, P < 0.05). The detection of one or more adenomatous polyps was higher after OSPS than after PEG. CONCLUSIONS: Renal failure was not detected after the use of OSPS for colonoscopy preparation in subjects with recently documented normal renal function who were able to consume the required amounts of water after each dose. However, based on the number of subjects studied, the theoretical risk of this complication is still between 0 and 6.3%. Thus, it is appreciated that only a very large prospective trial would have yielded a more accurate estimate of the likelihood of renal compromise after OSPS. Despite this caveat, OSPS has advantages over PEG in terms of the adequacy of colonic visualization and the number of polyps detected.
Assuntos
Injúria Renal Aguda/diagnóstico , Catárticos/administração & dosagem , Fosfatos/administração & dosagem , Polietilenoglicóis/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Catárticos/efeitos adversos , Distribuição de Qui-Quadrado , Colonoscopia/métodos , Feminino , Seguimentos , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Fosfatos/efeitos adversos , Polietilenoglicóis/administração & dosagem , Probabilidade , Estudos Prospectivos , Medição de Risco , Gestão da Segurança , Estatísticas não Paramétricas , Resultado do TratamentoRESUMO
Patients with acute spinal cord injury (SCI) with paralysis experience rapid and marked muscle atrophy below the level of the lesion. Muscle is lost above the lesion due to enforced bed rest associated with immobilization. Presently, there is no viable method to quantify muscle loss between the time of injury to the initiation of rehabilitation and remobilization. Furthermore, to assess the efficacy of any physical or pharmacological intervention necessitates the ability to accurately determine the impact of these treatments on muscle mass and function. Our results are presented from measurements of regional potassium (K) in the legs of persons with chronic SCI. The intracellular body K, comprising approximately 97% of the total body K, is indicative of the metabolically active cell mass, of which over 50% is located in the skeletal muscle (SM). To assess regional variations in SM mass in the legs, a partial body K (PBK) system designed for this purpose was placed on a potentially mobile cart. The SM mass measured by PBK in an able-bodied control cohort (n = 17) and in patients with chronic SCI (n = 21) was 17.6 +/- 0.86 and 11.0 +/- 0.65 kg, respectively, a difference of approximately 37.5%. However, the difference in the lean tissue mass of the legs obtained by dual-energy absorptiometry (DXA) in the same cohorts was 20.5 +/- 0.86 and 15.5 +/- 0.88 kg, respectively, or a difference of approximately 24.4%. PBK offers a novel approach to obtain regional K measurements in the legs, thus allowing the potential for early and serial assessment of muscle loss in SCI subjects during the acute and subacute periods following paralysis. The basic characteristics and performance of our PBK system and our calibration procedure are described in this preliminary report.
Assuntos
Composição Corporal , Pesos e Medidas Corporais/métodos , Músculo Esquelético/química , Atrofia Muscular/etiologia , Paralisia/etiologia , Potássio/análise , Traumatismos da Medula Espinal/metabolismo , Absorciometria de Fóton , Pesos e Medidas Corporais/instrumentação , Estudos de Casos e Controles , Doença Crônica , Desenho de Equipamento , Humanos , Perna (Membro) , Atrofia Muscular/metabolismo , Paralisia/metabolismo , Imagens de Fantasmas , Projetos Piloto , Radioisótopos de Potássio/análise , Reprodutibilidade dos Testes , Espectrometria gama , Traumatismos da Medula Espinal/complicaçõesRESUMO
BACKGROUND: Bone mineral density (BMD) of the lumbar spine (L-spine) has been reported to be normal or increased in persons with chronic spinal cord injury (SCI). OBJECTIVE: To determine BMD of the L-spine by dual-energy X-ray absorptiometry (DXA) and quantitative computerized tomography (qCT) in men with chronic SCI compared with able-bodied controls. DESIGN: Cross-sectional, comparative study. SETTING: Clinical research unit, Veterans Affairs Medical Center, Bronx, NY, USA and Kessler Institute of Rehabilitation, West Orange, NJ, USA. METHODS: Measurements of the L-spine were made in 20 men with SCI and compared with 15 able-bodied controls. The DXA images were acquired on a GE Lunar DPX-IQ. The qCT images of the L-spine were acquired on a Picker Q series computerized tomographic scanner. RESULTS: The mean ages for the SCI and control groups were 44+/-13 vs 42+/-9 years, and the duration of injury of the group with SCI was 14+/-11 years. There were no significant differences between the SCI and control groups for L-spine DXA BMD (1.391+/-0.210 vs 1.315+/-0.178 g/m(2)) or for L-spine DXA T-score (1.471+/-1.794 vs 0.782+/-1.481). L-spine qCT BMD was significantly lower in the SCI compared with the control group (1.296+/-0.416 vs 1.572+/-0.382 g/m(2), P=0.05); the T-score approached significance (-1.838+/-1.366 vs -0.963+/-1.227, P=0.059). Subjects with moderate degenerative joint disease (DJD) had significantly higher T-scores by DXA than those without or with mild DJD. CONCLUSION: Individuals with SCI who have moderate to severe DJD may have bone loss of the L-spine that may be underestimated by DXA, reducing awareness of the risk of fracture.