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1.
Front Physiol ; 9: 716, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30034341

RESUMO

Space flight-induced physiological deconditioning resulting from decreased gravitational input, decreased plasma volume, and disruption of regulatory mechanisms is a significant problem in returning astronauts as well as in normal aging. Here we review effects of a promising countermeasure on cardiovascular systems of healthy men and women undergoing Earth-based models of space-flight. This countermeasure is produced by a centrifuge and called artificial gravity (AG). Numerous studies have determined that AG improves orthostatic tolerance (as assessed by various protocols) of healthy ambulatory men, of men deconditioned by bed rest or by immersion (both wet and dry) and, in one case, following spaceflight. Although a few studies of healthy, ambulatory women and one study of women deconditioned by furosemide, have reported improvement of orthostatic tolerance following exposure to AG, studies of bed-rested women exposed to AG have not been conducted. However, in ambulatory, normovolemic subjects, AG training was more effective in men than women and more effective in subjects who exercised during AG than in those who passively rode the centrifuge. Acute exposure to an AG protocol, individualized to provide a common stimulus to each person, also improved orthostatic tolerance of normovolemic men and women and of furosemide-deconditioned men and women. Again, men's tolerance was more improved than women's. In both men and women, exposure to AG increased stroke volume, so greater improvement in men vs. women was due in part to their different vascular responses to AG. Following AG exposure, resting blood pressure (via decreased vascular resistance) decreased in men but not women, indicating an increase in men's vascular reserve. Finally, in addition to counteracting space flight deconditioning, improved orthostatic tolerance through AG-induced improvement of stroke volume could benefit aging men and women on Earth.

2.
Aerosp Med Hum Perform ; 88(9): 827-833, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28818141

RESUMO

BACKGROUND: Intermittent artificial gravity (AG) training over days and weeks has been shown to improve the human orthostatic tolerance limit (OTL) and improve cardiovascular regulation in response to orthostatic stress. Effects of a single AG exposure are currently unknown. METHODS: We tested cardiovascular responses to orthostatic stress in 16 hypovolemic subjects (9 men and 7 women), once following a single, short (∼90 min) bout of AG and once following a similar period of head-down bed rest (HDBR). Hypovolemia was produced by intravenous furosemide infusion (20 mg) and orthostatic stress was produced by combined 70° head-up tilt (HUT) and progressively increasing lower body negative pressure until symptoms of presyncope developed. To assess reflex-induced changes in cardiovascular regulation, heart rate and blood pressure variability were analyzed by spectral analysis and baroreflex activity was evaluated by transfer function analysis. RESULTS: Compared to HDBR, a short AG exposure increased men's low frequency (0.04-0.15 Hz) power of systolic blood pressure (SBPLF), but did not change women's SBPLF responses to orthostatic stress. In response to 70° HUT, compared to supine, low frequency phase delay (PhaseLF) between systolic blood pressure and RR intervals increased by ∼20% following HDBR, but did not change following AG, reflecting improved baroreflex activity at a milder level of orthostatic stress after AG. CONCLUSIONS: These results indicate that a short bout of AG increased both sympathetic and baroreflex responsiveness to orthostatic stress in hypovolemia-induced, cardiovascular-deconditioned men and women, which may contribute to the AG-induced improvement of OTL shown in our previous reports.Zhang Q, Evans JM, Stenger MB, Moore FB, Knapp CF. Autonomic cardiovascular responses to orthostatic stress after a short artificial gravity exposure. Aerosp Med Hum Perform. 2017; 88(9):827-833.


Assuntos
Sistema Nervoso Autônomo/fisiologia , Descondicionamento Cardiovascular/fisiologia , Gravidade Alterada , Decúbito Inclinado com Rebaixamento da Cabeça/fisiologia , Adulto , Barorreflexo/fisiologia , Repouso em Cama , Pressão Sanguínea/fisiologia , Feminino , Frequência Cardíaca/fisiologia , Hemodinâmica/fisiologia , Humanos , Hipovolemia/fisiopatologia , Pressão Negativa da Região Corporal Inferior , Masculino
3.
Front Physiol ; 8: 561, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28848448

RESUMO

Key Points Summary We report how blood pressure, cardiac output and vascular resistance are related to height, weight, body surface area (BSA), and body mass index (BMI) in healthy young adults at supine rest and standing.Much inter-subject variability in young adult's blood pressure, currently attributed to health status, may actually result from inter-individual body size differences.Each cardiovascular variable is linearly related to height, weight and/or BSA (more than to BMI).When supine, cardiac output is positively related, while vascular resistance is negatively related, to body size. Upon standing, the change in vascular resistance is positively related to size.The height/weight relationships of cardiac output and vascular resistance to body size are responsible for blood pressure relationships to body size.These basic components of blood pressure could help distinguish normal from abnormal blood pressures in young adults by providing a more effective scaling mechanism. Introduction: Effects of body size on inter-subject blood pressure (BP) variability are not well established in adults. We hypothesized that relationships linking stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) with body size would account for a significant fraction of inter-subject BP variability. Methods: Thirty-four young, healthy adults (19 men, 15 women) participated in 38 stand tests during which brachial artery BP, heart rate, SV, CO, TPR, and indexes of body size were measured/calculated. Results: Steady state diastolic arterial BP was not significantly correlated with any index of body size when subjects were supine. However, upon standing, the more the subject weighed, or the taller s/he was, the greater the increase in diastolic pressure. Systolic pressure strongly correlated with body weight and height both supine and standing. Diastolic and systolic BP were more strongly related to height, weight and body surface area than to body mass index. When supine: lack of correlation between diastolic pressure and body size, resulted from the combination of positive SV correlation and negative TPR correlation with body size. The positive systolic pressure vs. body size relationship resulted from a positive SV vs. height relationship. In response to standing: the positive diastolic blood pressure vs. body size relationship resulted from the standing-induced, positive increase in TPR vs. body size relationship. The relationships between body weight or height with SV and TPR contribute new insight into mechanisms of BP regulation that may aid in the prediction of health in young adults by providing a more effective way to scale BP with body size.

4.
Am J Dermatopathol ; 38(1): 56-62, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26317389

RESUMO

Syringocystadenocarcinoma papilliferum (SCACP) is an extremely rare adnexal neoplasm, believed to arise in a preexisting nevus sebaceus of Jadassohn (NSJ) through a multistep progression process. This hypothetical process involves an NSJ giving rise to syringocystadenoma papilliferum, which then presumably undergoes malignant transformation in rare circumstances to give rise to SCACP in situ, which finally progresses to an invasive SCACP. Of the 30 SCACP cases reported so far, none have documented the process from a birthmark to the final invasive lesion, with histological evidence of each step, in a single tumor. Here, the authors report just such a case. A 74-year-old man presented with a recently enlarging birthmark on the scalp. Excisional biopsy showed an invasive SCACP, in the background of SCACP in situ, syringocystadenoma papilliferum, and NSJ. Furthermore, this tumor showed a concurrent pigmented trichoblastoma and histological evidence of lymphovascular invasion, events that have not been documented with SCACP. Interestingly, all these component lesions were present on a single histological section of this solitary tumor. Regional lymph node metastasis, a rare occurrence in SCACP, was also present in this remarkable case. The authors discuss the implications of these findings in light of the review of relevant literature.


Assuntos
Carcinoma in Situ/patologia , Cistadenocarcinoma Papilar/patologia , Neoplasias de Cabeça e Pescoço/patologia , Nevo Sebáceo de Jadassohn/patologia , Couro Cabeludo , Neoplasias Cutâneas/patologia , Siringoma/patologia , Idoso , Transformação Celular Neoplásica , Cistadenocarcinoma Papilar/secundário , Humanos , Metástase Linfática , Masculino , Invasividade Neoplásica
5.
Am J Dermatopathol ; 38(1): 66-72, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26258878

RESUMO

T lymphocytes belong to 2 distinct sublineages that express either αß or γδ T-cell receptor (TCR) complex. Although malignancy is a great instigator of lineage infidelity, as exemplified by aberrant expression of numerous lineage markers in lymphoma cells, malignant T cells rarely coexpress αß and γδ TCR complexes. Similarly, only rare cases of CD4/CD8 double-positive primary cutaneous T-cell lymphoma have been reported. In this report, we describe a remarkable case of primary cutaneous T-cell lymphoma coexpressing αß and γδ TCR complexes, strong diffuse CD8, and a very restricted coexpression of CD4 and CD8. A 66-year-old man was referred to our center for treatment of a persistent eczematoid eruption of 6 years of duration. An initial biopsy demonstrated not only marked spongiosis, but also an epidermotropic population of CD4 small mature T cells with partial expression of CD8. The process remained indolent for another year, followed by an abrupt progression with development of plaques and tumors. Repeat biopsies of these lesions demonstrated a superimposed population of large anaplastic T cells extensively involving the dermis and epidermis. The large cells showed a strong uniform expression of CD3, CD8, CD45RA, CD5, granzyme, TIA1, perforin, TCR-ß, and TCR-γ and a weaker but unambiguous expression of CD4, CD25, CD2, and CD56. TCR gene rearrangement studies showed clonal rearrangements for TCR-ß and TCR-γ with identical peaks to those seen in the biopsy from a year earlier. The patient developed lymphadenopathy, with a biopsy showing nodal involvement by a morphologically and phenotypically identical neoplastic T-cell population. The disease showed partial response to systemic chemotherapy with development of new plaques, but these new lesions have regressed with radiation therapy.


Assuntos
Antígenos CD/análise , Linfoma Cutâneo de Células T/química , Linfoma Cutâneo de Células T/patologia , Receptores de Antígenos de Linfócitos T alfa-beta/análise , Receptores de Antígenos de Linfócitos T gama-delta/análise , Idoso , Granzimas/análise , Humanos , Masculino , Perforina/análise , Proteínas de Ligação a Poli(A)/análise , Antígeno-1 Intracelular de Células T
6.
Eur J Appl Physiol ; 115(12): 2631-40, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26438067

RESUMO

PURPOSE: In addition to serious bone, vestibular, and muscle deterioration, space flight leads to cardiovascular dysfunction upon return to gravity. In seeking a countermeasure to space flight-induced orthostatic intolerance, we previously determined that exposure to artificial gravity (AG) training in a centrifuge improved orthostatic tolerance of ambulatory subjects. This protocol was more effective in men than women and more effective when subjects exercised. METHODS: We now determine the orthostatic tolerance limit (OTL) of cardiovascularly deconditioned (furosemide) men and women on one day following 90 min of AG compared to a control day (90 min of head-down bed rest, HDBR). RESULTS: There were three major findings: a short bout of artificial gravity improved orthostatic tolerance of hypovolemic men (30 %) and women (22 %). Men and women demonstrated different mechanisms of cardiovascular regulation on AG and HDBR days; women maintained systolic blood pressure the same after HDBR and AG exposure while men's systolic pressure dropped (11 ± 2.9 mmHg) after AG. Third, as presyncopal symptoms developed, men's and women's cardiac output and stroke volume dropped to the same level on both days, even though the OTL test lasted significantly longer on the AG day, indicating cardiac filling as a likely variable to trigger presyncope. CONCLUSIONS: (1) Even with gender differences, AG should be considered as a space flight countermeasure to be applied to astronauts before reentry into gravity, (2) men and women regulate blood pressure during an orthostatic stress differently following exposure to artificial gravity and (3) the trigger for presyncope may be cardiac filling.


Assuntos
Pressão Sanguínea , Hipovolemia/fisiopatologia , Intolerância Ortostática/fisiopatologia , Ausência de Peso/efeitos adversos , Adulto , Feminino , Humanos , Hipovolemia/etiologia , Masculino , Intolerância Ortostática/etiologia , Fatores Sexuais
7.
Eur J Appl Physiol ; 115(2): 417-27, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25344797

RESUMO

We investigated whether and how cardiovascular and cardiorespiratory phase synchronization would respond to changes in hydration status and orthostatic stress. Four men and six women were tested during graded head-up tilt (HUT) in both euhydration and dehydration (DEH) conditions. Continuous R-R intervals (RRI), systolic blood pressure (SBP) and respiration were investigated in low (LF 0.04-0.15 Hz) and high (HF 0.15-0.4 Hz) frequency ranges using a phase synchronization index (λ) ranging from 0 (complete lack of interaction) to 1 (perfect interaction) and a directionality index (d), where a positive value of d reflects oscillator 1 driving oscillator 2, and a negative value reflects the opposite driving direction. Surrogate data analysis was used to exclude relationships that occurred by chance. In the LF range, respiration was not synchronized with RRI or SBP, whereas RRI and SBP were phase synchronized. In the HF range, phases among all variables were synchronized. DEH reduced λ among all variables in the HF and did not affect λ between RRI and SBP in the LF region. DEH reduced d between RRI and SBP in the LF and did not affect d among all variables in the HF region. Increasing λ and decreasing d between SBP and RRI were observed in the LF range during HUT. Decreasing λ between SBP and RRI, respiration and RRI, and decreasing d between respiration and SBP were observed in the HF range during HUT. These results show that orthostatic stress disassociated interactions among RRI, SBP and respiration, and that DEH exacerbated the disconnection.


Assuntos
Pressão Sanguínea , Desidratação/fisiopatologia , Hipotensão Ortostática/fisiopatologia , Hipovolemia/fisiopatologia , Respiração , Adulto , Feminino , Humanos , Masculino , Decúbito Dorsal
8.
Eur J Appl Physiol ; 115(2): 257-68, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25272970

RESUMO

PURPOSE: Harmful effects of inhaled particulates have been established in epidemiologic studies of ambient air pollution. In particular, heart rate variability responses to high levels of environmental tobacco smoke (ETS), similar to responses observed during direct smoking, have been reported. We sought to determine whether such responses could be observed at lower particulate concentrations. METHODS: We monitored cardiovascular responses of non-smoking 21 women and 19 men to work-place-relevant levels of: ETS, cooking oil fumes (Coil), wood smoke (WS), and water vapor as sham control. Responses, tested on three consecutive days (random order of aerosol presentation), were averaged for each subject. RESULTS: Low frequency spectral powers of heart rate and blood pressure rose during recovery from exposure to particulate, but not to sham exposures. At breathing frequencies, spectral power of men's systolic pressure doubled, and baroreflex effectiveness increased, following ETS exposure. An index of sympathetic control of heart rate was more pronounced in men than women, in response to ETS and Coil, compared to WS and sham. CONCLUSIONS: When measured under controlled conditions, autonomic activities in non-smoking men and women exposed to low level, short term, particulate concentrations were similar to those observed during longer term, higher level exposures to ETS and to direct smoking. These increased indexes of sympathetic control of heart rate and peripheral vasomotion followed introduction of particulates by about 15 min. Finally, coupling of heart rate and systolic pressure indicated an increase in baroreflex activity in the response to breathing ETS that was less effective in men than women.


Assuntos
Sistema Nervoso Autônomo/efeitos dos fármacos , Fumaça/efeitos adversos , Adulto , Sistema Nervoso Autônomo/fisiologia , Barorreflexo , Pressão Sanguínea , Feminino , Frequência Cardíaca , Humanos , Masculino
9.
Aviat Space Environ Med ; 85(4): 407-13, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24754201

RESUMO

BACKGROUND: Earth-based simulations of physiologic responses to space mission activities are needed to develop prospective countermeasures. To determine whether upright lower body positive pressure (LBPP) provides a suitable space mission simulation, we investigated the cardiovascular responses of normovolemic and hypovolemic men and women to supine and orthostatic stress induced by head-up tilt (HUT) and upright LBPP, representing standing in lunar, Martian, and Earth gravities. METHODS: Six men and six women were tested in normovolemic and hypovolemic (furosemide, intravenous, 0.5 mg x kg(-1)) conditions. Continuous electrocardiogram, blood pressure, segmental bioimpedance, and stroke volume (echocardiography) were recorded supine and at lunar, Martian, and Earth gravities (10 degrees, 20 degrees, and 80 degrees HUT vs. 20%, 40%, and 100% bodyweight upright LBPP), respectively. Cardiovascular responses were assessed from mean values, spectral powers, and spontaneous baroreflex parameters. RESULTS: Hypovolemia reduced plasma volume by approximately 10% and stroke volume by approximately 25% at supine, and increasing orthostatic stress resulted in further reductions. Upright LBPP induced more plasma volume losses at simulated lunar and Martian gravities compared with HUT, while both techniques induced comparable central hypovolemia at each stress. Cardiovascular responses to orthostatic stress were comparable between HUT and upright LBPP in both normovolemic and hypovolemic conditions; however, hypovolemic blood pressure was greater during standing at 100% bodyweight compared to 80 degree HUT due to a greater increase of total peripheral resistance. CONCLUSIONS: The comparable cardiovascular response to HUT and upright LBPP support the use of upright LBPP as a potential model to simulate activity in lunar and Martian gravities.


Assuntos
Fenômenos Fisiológicos Cardiovasculares , Gravidade Alterada/efeitos adversos , Hipovolemia/fisiopatologia , Simulação de Ambiente Espacial , Estresse Fisiológico/fisiologia , Adulto , Pressão Sanguínea/fisiologia , Estudos de Casos e Controles , Planeta Terra , Eletrocardiografia , Feminino , Gravitação , Frequência Cardíaca/fisiologia , Humanos , Masculino , Marte , Lua , Postura/fisiologia , Voo Espacial , Volume Sistólico/fisiologia , Resistência Vascular/fisiologia , Adulto Jovem
10.
Aviat Space Environ Med ; 85(4): 414-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24754202

RESUMO

INTRODUCTION: In this study we compare two models [head-up tilt (HUT) vs. body unweighting using lower body positive pressure (LBPP)] to simulate Moon, Mars, and Earth gravities. A literature search did not reveal any comparisons of this type performed previously. We hypothesized that segmental fluid volume shifts (thorax, abdomen, upper and lower leg), cardiac output, and blood pressure (BP), heart rate (HR), and total peripheral resistance to standing would be similar in the LBPP and HUT models. METHODS: There were 21 subjects who were studied while supine (simulation of spaceflight) and standing at 100% (Earth), 40% (Mars), and 20% (Moon) bodyweight produced by LBPP in Alter-G and while supine and tilted at 80 degrees, 20 degrees, and 10 degrees HUT (analogues of Earth, Mars, and Moon gravities, respectively). RESULTS: Compared to supine, fluid shifts from the chest to the abdomen, increases in HR, and decreases in stroke volume were greater at 100% bodyweight than at reduced weights in response to both LBPP and HUT. Differences between the two models were found for systolic BP, diastolic BP, mean arterial BP, stroke volume, total peripheral resistance, and thorax and abdomen impedances, while HR, cardiac output, and upper and lower leg impedances were similar. CONCLUSIONS: Bodyweight unloading via both LBPP and HUT resulted in cardiovascular changes similar to those anticipated in actual reduced gravity environments. The LBPP model/Alter-G has the advantage of providing an environment that allows dynamic activity at reduced bodyweight; however, the significant increase in blood pressures in the Alter-GC may favor the HUT model.


Assuntos
Fenômenos Fisiológicos Cardiovasculares , Gravidade Alterada , Simulação de Ambiente Espacial/métodos , Adulto , Pressão Sanguínea/fisiologia , Débito Cardíaco/fisiologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Marte , Modelos Cardiovasculares , Lua , Intolerância Ortostática , Postura/fisiologia , Voo Espacial , Volume Sistólico/fisiologia , Resistência Vascular/fisiologia , Adulto Jovem
11.
J Drugs Dermatol ; 13(4): 489-91, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24719070

RESUMO

Porphyria cutanea tarda (PCT) is a blistering skin disorder that occurs most commonly in middle-aged individuals. It is caused by decreased uroporphyrinogen decarboxylase (UROD) activity, which results in elevated levels of uroporphyrinogen. Occurrence remains very rare in children with some sources quoting as few as 50 reports of childhood cases.1 The literature reports occasional cases of PCT onset with various drugs, including barbiturates, estrogens, griseofulvin, rifampicin, sulfonamides, imatinib, methotrexate, tamoxifen, and cyclophosphamide, however its incidence in childhood is uncommon.2-6 We present a case of new-onset PCT in an eight year-old following treatment of pre-B cell acute lymphoblastic leukemia with multi-agent chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Porfiria Cutânea Tardia/induzido quimicamente , Criança , Feminino , Humanos , Hipertricose/induzido quimicamente , Flebotomia , Porfiria Cutânea Tardia/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico
12.
Aviat Space Environ Med ; 84(11): 1140-6, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24279226

RESUMO

BACKGROUND: We hypothesized that human cardiovascular responses to standing in reduced gravity environments, as on the Moon or Mars, could be modeled using a lower body positive pressure (LBPP) chamber. METHODS: Heart rate, blood pressure, body segment fluid shifts, ECG, indexes of sympathetic, parasympathetic balance, and baroreflex control of the heart and periphery plus echocardiographic measures of cardiac function were recorded from seven men and seven women supine and standing at 100% (Earth), 40% (-Mars), and 20% (-Moon) bodyweights (BW). RESULTS: The fluid shifted from the chest was greater when standing at 100% BW than at 20% and 40% BW, while fluid pooled in the abdomen was similar at all BWs. Compared to moving from supine to standing at 100% BW, moving to 20% and 40% BW resulted in smaller decreases in stroke volume and pulse pressure, smaller increases in heart rate and smaller decreases in parasympathetic control of heart rate, baroreflex slope, numbers of blood pressure ramps, and much reduced indexes of sympathetic drive to the heart and periphery. However, peripheral vascular resistance, systolic pressure, and baroreflex effectiveness were elevated during 20% and 40% BW, compared to supine and standing at 100% BW. DISCUSSION: Standing at reduced bodyweight suppressed indexes of sympathetic control of heart rate and peripheral vasomotion. Regulatory responses indicated a combination of arterial and cardiopulmonary baroreflex control: mean heart rate, vasomotion, and baroreflex sensitivity appeared to be more under cardiopulmonary control while baroreflex effectiveness appeared to be driven more by the arterial baroreflex.


Assuntos
Barorreflexo/fisiologia , Pressão Sanguínea/fisiologia , Hipogravidade , Voo Espacial , Sistema Cardiovascular , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Volume Sistólico/fisiologia , Resistência Vascular/fisiologia
13.
Am J Dermatopathol ; 34(6): 592-6, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22814318

RESUMO

Merkel cell carcinoma (MCC) is a rare but highly aggressive cutaneous malignancy with a mortality rate exceeding that of melanoma. Although smaller studies of markers of progression have been performed, large-scale investigation has been difficult due to the rarity of this tumor. Investigation of 4 potential immunohistochemical progression markers using an MCC tissue microarray was performed. An immunohistochemical analysis of CXCR4, E-cadherin, Bcl-2, and Survivin was performed on a tissue microarray of two hundred twenty-seven 0.6-mm tumor cores-110 primary, 73 local/regional metastatic, and 44 distant metastatic-from 87 patients, 23 of which were sampled 2 or more times. There was a statistically significant increase in immunoreactivity to CXCR4 and Survivin in local/regional nodal MCC metastases compared with primary and distant metastatic lesions. No significant differences by disease location were found for either Bcl-2 or E-cadherin. These results suggest a potential role for CXCR4 and Survivin in MCC tumor progression. However, previous data from other studies suggesting a role for Bcl-2 and E-cadherin in MCC progression are not confirmed in this larger sample. Further discovery of additional markers are needed to better characterize this rare but deadly malignancy.


Assuntos
Biomarcadores Tumorais/metabolismo , Caderinas/metabolismo , Carcinoma de Célula de Merkel/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptores CXCR4/metabolismo , Neoplasias Cutâneas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Caderinas/genética , Carcinoma de Célula de Merkel/patologia , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Proteínas Inibidoras de Apoptose/genética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas c-bcl-2/genética , Receptores CXCR4/genética , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Survivina , Análise Serial de Tecidos
15.
Am J Dermatopathol ; 34(3): e37-9, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22356917

RESUMO

Mycosis fungoides (MF) is a primary cutaneous lymphoma characterized by atypical T-lymphocytes that usually presents as patches and plaques on photoprotected areas of the body, such as the groin and buttocks. Classically, the atypical lymphocytes in MF are CD3/CD4 positive with loss of CD7 and less often loss of CD5. In a minority of cases, the atypical infiltrate is CD8 positive. We report a case of biopsy-proven MF in an elderly woman who presented with sclerodermoid lesions on her abdomen and thigh. Immunohistochemical studies revealed coexpression of CD4 and CD8 in a subset of atypical T-lymphocytes, and this was confirmed with flow cytometry. To our knowledge, this is the first report of a CD4/CD8 dual-positive MF.


Assuntos
Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Micose Fungoide/patologia , Neoplasias Cutâneas/patologia , Idoso , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Terapia Combinada , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Imunofenotipagem , Micose Fungoide/imunologia , Micose Fungoide/terapia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/terapia , Resultado do Tratamento
16.
Eur J Appl Physiol ; 112(2): 605-16, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21626041

RESUMO

We studied 15 men (8 treatment, 7 control) before and after 21 days of 6º head-down tilt to determine whether daily, 1-h exposures to 1.0 G(z) (at the heart) artificial gravity (AG) would prevent bed rest-induced cardiovascular deconditioning. Testing included echocardiographic analysis of cardiac function, plasma volume (PV), aerobic power (VO(2)pk) and cardiovascular and neuroendocrine responses to 80º head-up tilt (HUT). Data collected during HUT were ECG, stroke volume (SV), blood pressure (BP) and blood for catecholamines and vasoactive hormones. Heart rate (HR), cardiac output (CO), total peripheral resistance, and spectral power of BP and HR were calculated. Bed rest decreased PV, supine and HUT SV, and indices of cardiac function in both groups. Although PV was decreased in control and AG after bed rest, AG attenuated the decrease in orthostatic tolerance [pre- to post-bed rest change; control: -11.8 ± 2.0, AG: -6.0 ± 2.8 min (p = 0.012)] and VO(2)pk [pre- to post-bed rest change; control: -0.39 ± 0.11, AG: -0.17 ± 0.06 L/min (p = 0.041)]. AG prevented increases in pre-tilt levels of plasma renin activity [pre- to post-bed rest change; control: 1.53 ± 0.23, AG: -0.07 ± 0.34 ng/mL/h (p = 0.001)] and angiotensin II [pre- to post-bed rest change; control: 3.00 ± 1.04, AG: -0.63 ± 0.81 pg/mL (p = 0.009)] and increased HUT aldosterone [post-bed rest; control: 107 ± 30 pg/mL, AG: 229 ± 68 pg/mL (p = 0.045)] and norepinephrine [post-bed rest; control: 453 ± 107, AG: 732 ± 131 pg/mL (p = 0.003)]. We conclude that AG can mitigate some aspects of bed rest-induced cardiovascular deconditioning, including orthostatic intolerance and aerobic power. Mechanisms of improvement were not cardiac-mediated, but likely through improved sympathetic responsiveness to orthostatic stress.


Assuntos
Repouso em Cama/efeitos adversos , Terapia por Exercício , Gravidade Alterada , Coração/fisiopatologia , Miocárdio/patologia , Esforço Físico , Aptidão Física , Adulto , Atrofia , Feminino , Humanos , Masculino
17.
Am J Physiol Regul Integr Comp Physiol ; 302(5): R541-50, 2012 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-22049233

RESUMO

Cardiac and vascular dysfunctions resulting from autonomic neuropathy (AN) are complications of diabetes, often undiagnosed. Our objectives were to: 1) determine sympathetic and parasympathetic components of compromised blood pressure (BP) regulation in patients with peripheral neuropathy and 2) rank noninvasive indexes for their sensitivity in diagnosing AN. We continuously measured electrocardiogram, arterial BP, and respiration during supine rest and 70° head-up tilt in 12 able-bodied subjects, 7 diabetics without, 7 diabetics with possible, and 8 diabetics with definite, sensory, and/or motor neuropathy (D2). During the first 3 min of tilt, systolic BP (SBP) of D2 decreased [-10.9 ± 4.5 (SE) mmHg] but increased in able-bodied (+4.8 ± 5.4 mmHg). Compared with able-bodied, D2 had smaller low-frequency (0.04-0.15 Hz) spectral power of diastolic BP, lower baroreflex effectiveness index (BEI), and more SBP ramps. Except for low-frequency power of SBP, D2 had greater SBP and smaller RR interval harmonic and nonharmonic components at rest across the 0.003- to 0.45-Hz region. In addition, our results support previous findings of smaller HF RR interval power, smaller numbers of baroreflex sequences, and lower baroreflex sensitivity in D2. We conclude that diabetic peripheral neuropathy is accompanied by diminished parasympathetic and sympathetic control of heart rate and peripheral vasomotion and diminished baroreflex regulation. A novel finding of this study lies in the sensitivity of BEI to detect AN, presumably because of its combination of parameters that measure reductions in both sympathetic control of vasomotion and parasympathetic control of heart rate.


Assuntos
Pressão Sanguínea/fisiologia , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Adulto , Barorreflexo/fisiologia , Estudos de Casos e Controles , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Sistema Nervoso Parassimpático/fisiologia , Caracteres Sexuais , Sistema Nervoso Simpático/fisiologia , Sistema Vasomotor/fisiologia
20.
Am J Physiol Regul Integr Comp Physiol ; 292(3): R1146-57, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17082357

RESUMO

We investigated autonomic control of cardiovascular function in able-bodied (AB), paraplegic (PARA), and tetraplegic (TETRA) subjects in response to head-up tilt following spinal cord injury. We evaluated spectral power of blood pressure (BP), baroreflex sensitivity (BRS), baroreflex effectiveness index (BEI), occurrence of systolic blood pressure (SBP) ramps, baroreflex sequences, and cross-correlation of SBP with heart rate (HR) in low (0.04-0.15 Hz)- and high (0.15-0.4 Hz)-frequency regions. During tilt, AB and PARA effectively regulated BP and HR, but TETRA did not. The numbers of SBP ramps and percentages of heartbeats involved in SBP ramps and baroreflex sequences increased in AB, were unchanged in PARA, and declined in TETRA. BRS was lowest in PARA and declined with tilt in all groups. BEI was greatest in AB and declined with tilt in all groups. Low-frequency power of BP and the peak of the SBP/HR cross-correlation magnitude were greatest in AB, increased during tilt in AB, remained unchanged in PARA, and declined in TETRA. The peak cross-correlation magnitude in HF decreased with tilt in all groups. Our data indicate that spinal cord injury results in decreased stimulation of arterial baroreceptors and less engagement of feedback control as demonstrated by lower 1) spectral power of BP, 2) number (and percentages) of SBP ramps and barosequences, 3) cross-correlation magnitude of SBP/HR, 4) BEI, and 5) changes in delay between SBP/HR. Diminished vasomotion and impaired baroreflex regulation may be major contributors to decreased orthostatic tolerance following injury.


Assuntos
Sistema Nervoso Autônomo/fisiologia , Barorreflexo , Pressão Sanguínea , Paraplegia/fisiopatologia , Postura , Quadriplegia/fisiopatologia , Adulto , Estudos de Casos e Controles , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Teste da Mesa Inclinada , Fatores de Tempo
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