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1.
Am J Physiol Endocrinol Metab ; 325(1): E32-E45, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37224469

RESUMO

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.


Assuntos
Tecido Adiposo Marrom , Peromyscus , Animais , Tecido Adiposo Marrom/metabolismo , Meios de Cultivo Condicionados , Termogênese/fisiologia , Homeostase
2.
Osteoporos Int ; 30(11): 2241-2248, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31410501

RESUMO

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.


Assuntos
Osteoporose/diagnóstico , Osteoporose/etiologia , Doenças da Medula Espinal/complicações , Traumatismos da Medula Espinal/complicações , Veteranos , Absorciometria de Fóton , Adulto , Idoso , Conservadores da Densidade Óssea/uso terapêutico , Técnicas de Laboratório Clínico , Registros Eletrônicos de Saúde , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/tratamento farmacológico , Encaminhamento e Consulta , Estados Unidos , United States Department of Veterans Affairs
3.
Osteoporos Int ; 28(3): 925-934, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27924381

RESUMO

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.


Assuntos
Fraturas por Osteoporose/etiologia , Traumatismos da Medula Espinal/complicações , Absorciometria de Fóton , Adulto , Idoso , Densidade Óssea/fisiologia , Feminino , Articulação do Quadril/fisiopatologia , Humanos , Vértebras Lombares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Osteoporose/etiologia , Osteoporose/fisiopatologia , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/fisiopatologia , Valor Preditivo dos Testes , Sistema de Registros , Estudos Retrospectivos , Medição de Risco/métodos , Traumatismos da Medula Espinal/epidemiologia , Traumatismos da Medula Espinal/fisiopatologia , Estados Unidos/epidemiologia , United States Department of Veterans Affairs
4.
Osteoporos Int ; 27(10): 3011-21, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27230522

RESUMO

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.


Assuntos
Fraturas por Osteoporose/epidemiologia , Traumatismos da Medula Espinal/complicações , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Paraplegia/complicações , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Veteranos
5.
Spinal Cord ; 53(5): 402-7, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25622728

RESUMO

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.


Assuntos
Gerenciamento Clínico , Fraturas Ósseas/etiologia , Fraturas Ósseas/cirurgia , Traumatismos da Medula Espinal/complicações , Idoso , Doença Crônica , Fraturas Ósseas/epidemiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Traumatismos da Medula Espinal/epidemiologia , Estatísticas não Paramétricas , Estados Unidos , United States Department of Veterans Affairs , Veteranos
6.
Osteoporos Int ; 24(8): 2261-7, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23392311

RESUMO

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.


Assuntos
Fraturas Ósseas/complicações , Extremidade Inferior/lesões , Traumatismos da Medula Espinal/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Delírio/epidemiologia , Delírio/etiologia , Depressão/epidemiologia , Depressão/etiologia , Fraturas Ósseas/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Úlcera por Pressão/epidemiologia , Úlcera por Pressão/etiologia , Sistema de Registros , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/etiologia , Traumatismos da Medula Espinal/epidemiologia , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Estados Unidos/epidemiologia , Infecções Urinárias/epidemiologia , Infecções Urinárias/etiologia , Adulto Jovem
7.
Spinal Cord ; 51(2): 109-15, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23147130

RESUMO

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.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Traumatismos da Medula Espinal/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Veteranos , Saúde dos Veteranos
9.
Spinal Cord ; 50(9): 682-5, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22508535

RESUMO

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.


Assuntos
Transtornos do Sono-Vigília/epidemiologia , Doenças da Medula Espinal/complicações , Doenças da Medula Espinal/epidemiologia , Traumatismos da Medula Espinal/complicações , Veteranos , Idoso , Comorbidade , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Transtornos do Sono-Vigília/etiologia , Traumatismos da Medula Espinal/epidemiologia
10.
Public Health ; 126(10): 896-903, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22795651

RESUMO

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.


Assuntos
Esclerose Múltipla/prevenção & controle , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Serviços Preventivos de Saúde/estatística & dados numéricos , Veteranos/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos
11.
Artigo em Inglês | MEDLINE | ID: mdl-36518619

RESUMO

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.

12.
Science ; 184(4139): 899-901, 1974 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-17782382

RESUMO

Scanning electron microscope techniques show that Eocene opaline claystones (fuller's earth and buhrstone) of the Atlantic and Gulf Coastal Plain, deposits long considered volcanic in origin, are actually highly altered diatomites formed as transgressive facies in normal marine continental shelf environmnents. These findings are in agreement with a biogenic origin for time-equivalent horizon A and A deep-sea cherts of the North Atlantic and Caribbean.

13.
Spinal Cord ; 47(8): 610-5, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19238165

RESUMO

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.


Assuntos
Bacteriemia/epidemiologia , Bacteriemia/etiologia , Traumatismos da Medula Espinal/complicações , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/etiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Neuron ; 12(3): 615-26, 1994 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8155323

RESUMO

Three different experimental approaches were used to establish that the first transmembrane segment (S1) is important for K+ channel assembly. First, hydrodynamic analyses of in vitro translated Kv1.1 N-terminal domain containing the S1 segment coassembles to form homotetrameric complexes, whereas deletion of the S1 segment abolishes coassembly. Second, coimmunoprecipitation experiments of cotranslated Kv1.1 and Kv1.5 truncated polypeptides show that the S1 segment is essential for coimmunoprecipitation. Third, dominant negative experiments in Xenopus oocytes confirm that over-expression of either the S1 segment or the N-terminal domain is sufficient for abolishing the expression of functional Kv1.1 and Kv1.5 K+ channels. These data indicate that S1 segment plays an important role in the coassembly of homo- and heterotetrameric K+ channels.


Assuntos
Ativação do Canal Iônico , Canais de Potássio/fisiologia , Transdução de Sinais , Sequência de Aminoácidos , Animais , Sequência de Bases , Eletrofisiologia , Membranas/fisiologia , Dados de Sequência Molecular , Oócitos/metabolismo , Canais de Potássio/química , Canais de Potássio/genética , Ratos , Xenopus
15.
Oncogene ; 25(5): 769-80, 2006 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-16205642

RESUMO

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.


Assuntos
Sobrevivência Celular/genética , Receptor EphB4/genética , Neoplasias da Bexiga Urinária/genética , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular/genética , Primers do DNA , Receptores ErbB/metabolismo , Humanos , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismo , Neoplasias da Bexiga Urinária/patologia
16.
J Clin Invest ; 92(2): 720-6, 1993 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8349811

RESUMO

To determine whether hemodynamic changes can modulate insulin action in vivo, we administered angiotensin II (AII) to normal men under three separate, euglycemic conditions. First, in the presence of physiological hyperinsulinemia (approximately 115 microU/ml), infusion of AII at rates of 2, 10, and 20 ng/min per kg caused significant elevations of blood pressure, whole-body glucose clearance, and plasma insulin concentrations in an AII dose-dependent manner. Second, in the presence of plasma insulin concentrations that stimulate glucose transport maximally (approximately 5,000 microU/ml), AII infusions increased whole-body glucose clearance without enhancing glucose extraction across the leg. Third, in the presence of basal insulin concentrations (approximately 13 microU/ml), AII infusions had no effect on whole-body glucose turnover or leg glucose extraction. Thus, AII enhanced whole-body glucose utilization without directly stimulating glucose transport in a major skeletal muscle bed. To evaluate a possible hemodynamic mechanism for the effects of AII on glucose utilization, we measured blood flow to two areas that differ in their sensitivity to insulin: the kidneys and the leg. We found that AII redistributed blood flow away from the predominantly insulin-independent tissues of the kidney and toward the insulin-sensitive tissues of the leg during both sham and hyperinsulinemic glucose clamps. The redistribution of flow had no effect on whole-body glucose turnover when leg glucose uptake was unstimulated (sham clamps). However, when leg glucose uptake was activated by insulin, the redistribution of flow caused a net increase in whole-body glucose utilization. Our findings indicate that hemodynamic factors can modulate insulin action in vivo. Furthermore, our results suggest that variable activity of the renin-angiotensin system may contribute to inconsistencies in the association between insulin resistance and hypertension.


Assuntos
Angiotensina II/farmacologia , Glicemia/metabolismo , Glucose/metabolismo , Hiperinsulinismo/metabolismo , Insulina/farmacologia , Adulto , Pressão Sanguínea/efeitos dos fármacos , Técnica Clamp de Glucose , Humanos , Hiperinsulinismo/sangue , Infusões Intravenosas , Insulina/administração & dosagem , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Circulação Renal/efeitos dos fármacos
17.
Arch Intern Med ; 150(6): 1274-80, 1990 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2112906

RESUMO

A randomized design was used to examine the cost-effectiveness of a Veterans Administration hospital-based home care program that case managed inpatient and outpatient care. Patients (N = 419) with two or more functional impairments or a terminal illness were randomized to hospital-based home care (n = 211) or customary care (n = 208). Functional status, satisfaction with care, and morale were measured at baseline and at 1 and 6 months after discharge from the hospital; health care utilization was tracked for 6 months. Findings included significantly higher (0.1 on a three-point scale) patient and caregiver satisfaction with care at 1 month and lower Veterans Administration and private sector hospital costs ($3000 vs $4245) for the experimental group. Net per person health care costs were also 13% lower in the experimental group. We conclude that this model of hospital-based home care is cost-effective and that its expansion to cover these two patient groups throughout the Veterans Administration system can improve patient care at no additional cost.


Assuntos
Assistência Domiciliar/economia , Hospitais de Veteranos/economia , Idoso , Comportamento do Consumidor , Análise Custo-Benefício , Custos e Análise de Custo , Humanos , Illinois , Tempo de Internação , Pessoa de Meia-Idade , Análise Multivariada , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
J Am Geriatr Soc ; 48(6): 677-81, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10855606

RESUMO

OBJECTIVES: To examine the role of physicians in the Veteran Affairs (VA) home-based primary care (HBPC) program and to identify variables that predict whether physicians make home visits and volume of home visits made. DESIGN: Descriptive and regression analyses of responses from a mail survey. PARTICIPANTS: Forty-five physicians affiliated with VA HBPC programs. MAIN SURVEY TOPICS: Self-reported work load, attitudes toward home care, reasons for home visits, administrative policies regarding physicians' role in patient care management, and time commitment to home care. RESULTS: A majority of physicians believed strongly in the importance of home care and made home visits for reasons consistent with their training. Physician attitude toward home care and preoccupation with office or hospital practice were related to whether or not physicians made home visits. Degree of preoccupation with office practice and amount of salary support from VA HBPC were significant predictors of the number of visits made (R2 = 0.44). CONCLUSIONS: These findings indicate that most physicians will make home visits if they believe that home care is valuable and if their time commitment is supported financially. Managed care plans that own and operate home care programs and have the capacity to transfer primary care management to physicians who derive financial support from the programs should find this information particularly relevant.


Assuntos
Atitude do Pessoal de Saúde , Serviços de Assistência Domiciliar , Visita Domiciliar , Padrões de Prática Médica , United States Department of Veterans Affairs , Idoso , Coleta de Dados , Humanos , Modelos Lineares , Salários e Benefícios , Estados Unidos , Carga de Trabalho
19.
Obstet Gynecol ; 97(6): 880-4, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11384689

RESUMO

OBJECTIVE: To examine the indications and surgical morbidity for women veterans who underwent hysterectomies in Department of Veterans Affairs Medical Centers (VAs). METHODS: Data on hysterectomies performed in VAs from 1991 to 1997 were abstracted from a surgical quality improvement program. RESULTS: Records of 1722 women who had hysterectomies in VAs over 6 years were examined. Women were predominately white (62%) and their average age was 42.5 years. Operations included abdominal (74%), vaginal (22%), and laparoscopic-assisted (4%) methods. The most common indications for surgery included uterine leiomyomas (31%), abnormal uterine bleeding (14%), and endometriosis (11%). Indications differed by race (P <.01); nonwhite women were most likely to have surgery for leiomyoma (51%), whereas white women had hysterectomies for leiomyomas (19%), abnormal bleeding (15%), endometriosis (13%), and genital prolapse (11%). The mean postoperative stay was significantly longer for abdominal hysterectomies (4.51 days) than either vaginal or laparoscopic-assisted hysterectomies (2.92 and 2.21 days, respectively; P <.001). The overall complication rate within 30 days was 9%, and the most frequent complication was urinary tract infection (3.3%). CONCLUSION: Women who underwent hysterectomies in VAs had low complication rates, comparable to hysterectomy complication rates in the United States generally.


Assuntos
Hospitais de Veteranos/estatística & dados numéricos , Histerectomia/métodos , Histerectomia/estatística & dados numéricos , Doenças Uterinas/cirurgia , Adulto , Idoso , Análise de Variância , Distribuição de Qui-Quadrado , Endometriose/diagnóstico , Endometriose/cirurgia , Feminino , Seguimentos , Humanos , Leiomioma/diagnóstico , Leiomioma/cirurgia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento , Estados Unidos/epidemiologia , Doenças Uterinas/diagnóstico , Hemorragia Uterina/diagnóstico , Hemorragia Uterina/cirurgia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/cirurgia
20.
Arch Surg ; 131(9): 942-7; discussion 947-8, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8790179

RESUMO

OBJECTIVE: To assess management of penetrating internal carotid artery (ICA) injuries. DESIGN: Retrospective review of institutional protocol. SETTING: Level 1 trauma center in a major urban area. PATIENTS: Sixty-one patients with penetrating ICA injuries. INTERVENTIONS: In the period 1975 to 1987 (group 1; n = 36), management was based on individual surgeons' preferences. Between 1988 and 1995 (group 2; n = 25), an algorithm was employed: (1) hemodynamically stable patients with suspected ICA injuries underwent a diagnostic angiography; (2) surgically accessible injuries were reconstructed regardless of neurologic status with 2 exceptions: (a) neurologically intact patients with ICA occlusion were treated by anticoagulation and mild pharmacological hypertension and (b) minimal nonocclusive injuries were managed nonoperatively and followed up by serial angiography or duplex ultrasonography; and (3) heparinization, shunting, and completion angiography were employed. MAIN OUTCOME MEASURES: Neurologic status at admission and discharge were compared by the Fisher exact test. RESULTS: In group 1, 24 patients (67%) presented neurologically intact, and 12 (33%) with a deficit. Sixteen injuries were managed nonoperatively, 14 were repaired, and 6 were ligated. At discharge 6 (17%) were improved, 24 (66%) were unchanged, 6 (17%) were worse. Four patients (11%) died of cerebrovascular causes. In group 2, 19 patients (76%) presented neurologically intact, and 6 (24%) with a deficit. Eleven injuries were managed nonoperatively, 12 were repaired, and 2 were ligated. A death occurred in a patient who arrested, was admitted to the hospital in a coma, and died before ICA repair. CONCLUSIONS: Neurologic outcome after ICA injury is enhanced by an algorithm predicated on the liberal use of angiography, a predefined surgical approach, and selective observation.


Assuntos
Lesões das Artérias Carótidas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Estudos Retrospectivos , Ferimentos e Lesões/complicações , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/terapia
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