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1.
BMC Pulm Med ; 21(1): 275, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34425811

RESUMO

BACKGROUND: How cigarette smoke (CS) and chronic obstructive pulmonary disease (COPD) affect severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection and severity is controversial. We investigated the effects of COPD and CS on the expression of SARS-CoV-2 entry receptor ACE2 in vivo in COPD patients and controls and in CS-exposed mice, and the effects of CS on SARS-CoV-2 infection in human bronchial epithelial cells in vitro. METHODS: We quantified: (1) pulmonary ACE2 protein levels by immunostaining and ELISA, and both ACE2 and/or TMPRSS2 mRNA levels by RT-qPCR in two independent human cohorts; and (2) pulmonary ACE2 protein levels by immunostaining and ELISA in C57BL/6 WT mice exposed to air or CS for up to 6 months. The effects of CS exposure on SARS-CoV-2 infection were evaluated after in vitro infection of Calu-3 cells and differentiated human bronchial epithelial cells (HBECs), respectively. RESULTS: ACE2 protein and mRNA levels were decreased in peripheral airways from COPD patients versus controls but similar in central airways. Mice exposed to CS had decreased ACE2 protein levels in their bronchial and alveolar epithelia versus air-exposed mice. CS treatment decreased viral replication in Calu-3 cells, as determined by immunofluorescence staining for replicative double-stranded RNA (dsRNA) and western blot for viral N protein. Acute CS exposure decreased in vitro SARS-CoV-2 replication in HBECs, as determined by plaque assay and RT-qPCR. CONCLUSIONS: ACE2 levels were decreased in both bronchial and alveolar epithelial cells from COPD patients versus controls, and from CS-exposed versus air-exposed mice. CS-pre-exposure potently inhibited SARS-CoV-2 replication in vitro. These findings urge to investigate further the controversial effects of CS and COPD on SARS-CoV-2 infection.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/enzimologia , Fumar Cigarros/metabolismo , Doença Pulmonar Obstrutiva Crônica/enzimologia , SARS-CoV-2/fisiologia , Fumaça , Idoso , Idoso de 80 Anos ou mais , Enzima de Conversão de Angiotensina 2/genética , Animais , Brônquios , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Gravidade do Paciente , Alvéolos Pulmonares , RNA Mensageiro/metabolismo , Mucosa Respiratória/metabolismo , Serina Endopeptidases/genética , Nicotiana , Replicação Viral
2.
bioRxiv ; 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33330864

RESUMO

INTRODUCTION: How cigarette smoke (CS) and chronic obstructive pulmonary disease (COPD) affect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severity is controversial. We investigated the protein and mRNA expression of SARS-CoV-2 entry receptor ACE2 and proteinase TMPRSS2 in lungs from COPD patients and controls, and lung tissue from mice exposed acutely and chronically to CS. Also, we investigated the effects of CS exposure on SARS-CoV-2 infection in human bronchial epithelial cells. METHODS: In Cohort 1, ACE2-positive cells were quantified by immunostaining in FFPE sections from both central and peripheral airways. In Cohort 2, we quantified pulmonary ACE2 protein levels by immunostaining and ELISA, and both ACE2 and TMPRSS2 mRNA levels by RT-qPCR. In C57BL/6 WT mice exposed to air or CS for up to 6 months, pulmonary ACE2 protein levels were quantified by triple immunofluorescence staining and ELISA. The effects of CS exposure on SARS-CoV-2 infection were evaluated after 72hr in vitro infection of Calu-3 cells. After SARS-CoV-2 infection, the cells were fixed for IF staining with dsRNA-specific J2 monoclonal Ab, and cell lysates were harvested for WB of viral nucleocapsid (N) protein. Supernatants (SN) and cytoplasmic lysates were obtained to measure ACE2 levels by ELISA. RESULTS: In both human cohorts, ACE2 protein and mRNA levels were decreased in peripheral airways from COPD patients versus both smoker and NS controls, but similar in central airways. TMPRSS2 levels were similar across groups. Mice exposed to CS had decreased ACE2 protein levels in their bronchial and alveolar epithelia versus air-exposed mice exposed to 3 and 6 months of CS. In Calu3 cells in vitro, CS-treatment abrogated infection to levels below the limit of detection. Similar results were seen with WB for viral N protein, showing peak viral protein synthesis at 72hr. CONCLUSIONS: ACE2 levels were decreased in both bronchial and alveolar epithelial cells from uninfected COPD patients versus controls, and from CS-exposed versus air-exposed mice. CS-pre-treatment did not affect ACE2 levels but potently inhibited SARS-CoV-2 replication in this in vitro model. These findings urge to further investigate the controversial effects of CS and COPD on SARS-CoV2 infection.

3.
Gene Ther ; 16(1): 127-35, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18784748

RESUMO

The development of clinically beneficial myocardial gene therapy has been slowed by reliance on the use of viral carriers and non-physiologic, constitutive gene expression. To specifically address these issues, we have developed a non-viral gene carrier, water-soluble lipopolymer (WSLP), and an ischemia-inducible plasmid construct expressing vascular endothelial growth factor (VEGF), pRTP801-VEGF, to treat myocardial ischemia and infarction. Rabbits underwent ligation of the circumflex artery followed by injection of (a) an ischemia-inducible VEGF gene construct in a WSLP carrier; (b) a constitutively expressed, or unregulated, SV-VEGF gene construct in a WSLP carrier; (c) WSLP carrier alone; or (d) no injection therapy. Following 4 weeks treatment, ligation alone resulted in infarction of 48+/-7% of the left ventricle. With injection of WSLP carrier alone, 49+/-6% of the left ventricle was infarcted (P=NS). The constitutively expressed gene construct, SV-VEGF, reduced the infarct size to 32+/-7% of the left ventricle (P=0.007). The ischemia-inducible gene construct, RTP801-VEGF, further reduced the infarct size to 13+/-4% of the left ventricle (P<0.001). The use of a non-viral carrier to deliver an ischemia-inducible VEGF construct is effective in the treatment of acutely ischemic myocardium.


Assuntos
Terapia Genética/métodos , Infarto do Miocárdio/terapia , Miocárdio/metabolismo , Transfecção/métodos , Fator A de Crescimento do Endotélio Vascular/genética , Animais , Apoptose , Linhagem Celular , Expressão Gênica , Injeções , Modelos Animais , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Miocárdio/patologia , Polímeros , Coelhos , Fator A de Crescimento do Endotélio Vascular/análise
4.
J Interferon Cytokine Res ; 21(1): 1-9, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11177575

RESUMO

Interleukin-18 (IL-18) and IL-12 have been shown to play an important role in the induction of interferon-gamma (IFN-gamma). IFN-gamma induces the proliferation of T cells and natural killer (NK) cells and augments the Th1 immune cascade. The role of IL-18 and IL-12 in the induction of IFN-gamma following allogeneic heart transplantation has not been described. We sought to characterize the IL-12 and IL-18 response to murine allogeneic heart transplantation, particularly with respect to IFN-gamma production and histologic transplant rejection. Forty-eight heterotopic heart transplants were performed in two groups of mice: syngeneic C3H/HeN to C3H/HeN mice and allogeneic BALB/C to C3H/HeN mice. Transplants were followed out to 2, 6, 10, and 14 days. Six transplants were performed in each group. Serum and splenic samples were used to evaluate the cytokine response by ELISA. Explanted heart tissue was processed for evidence of histologic rejection, and RT-PCR was performed to evaluate the IL-12, IL-18, and IFN-gamma signal qualitatively. Analysis of variance (ANOVA), Fisher's projected least significant difference (PLSD) was used for statistical analysis. Transplant rejection occurred in the allogeneic group histologically by day 6 and clinically by day 10. Serum IFN-gamma levels rose significantly by day 6 in the allogeneic group and then continued to rise in the splenocyte cultures. Serum IL-18 also rose significantly in the allogeneic group at day 6 compared with syngeneic group. RT-PCR revealed that the allogeneic tissue contained an increased signal for IL-12, IL-18, and IFN-gamma beginning at day 6 and peaking at day 10 after transplant. Beginning 6 days after transplantation, IL-12 and IL-18 appear to play a significant role in the induction of IFN-gamma in allogeneic heart transplants.


Assuntos
Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Transplante de Coração/imunologia , Transplante de Coração/patologia , Interferon gama/biossíntese , Interleucina-18/biossíntese , Animais , Complexo CD3/análise , Rejeição de Enxerto/fisiopatologia , Transplante de Coração/estatística & dados numéricos , Interferon gama/sangue , Interferon gama/genética , Interleucina-12/sangue , Interleucina-12/genética , Interleucina-18/sangue , Interleucina-18/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Baço/citologia , Baço/imunologia , Baço/metabolismo , Transplante Homólogo , Transplante Isogênico
5.
J Thorac Cardiovasc Surg ; 119(2): 242-50, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10649199

RESUMO

OBJECTIVE: Inflammatory cytokines, particularly tumor necrosis factor, contribute to myocardial dysfunction after ischemia-reperfusion injury. Aprotinin may improve outcomes in cardiac surgery through suppression of inflammatory mediators. We hypothesized that aprotinin may exert its beneficial effects through suppression of tumor necrosis factor alpha. METHODS: Adult rat hearts were precision cut into slices with a thickness of 200 microm and stored in crystalloid cardioplegic solution alone or with one of the following additions: aprotinin or tumor necrosis factor alpha, aprotinin plus tumor necrosis factor alpha, a monoclonal antibody to tumor necrosis factor alpha, or a polyclonal antibody to the tumor necrosis factor alpha receptor. Myocardial biochemical function was assessed by adenosine triphosphate content and capacity for protein synthesis immediately after slicing (0 hours) and after 2, 4, and 6 hours of storage at 4 degrees C. The content of tumor necrosis factor alpha was measured by an enzyme-linked immunosorbent assay. Six slices were assayed at each time point for each solution. The data were analyzed by analysis of variance and are expressed as the mean +/- standard deviation. RESULTS: When stored in cardioplegic solution containing aprotinin, the heart slices demonstrated (1) an increase in adenosine triphosphate content and protein synthesis (P <.0001), (2) a decrease in intramyocardial generation of tumor necrosis factor alpha (P

Assuntos
Aprotinina/farmacologia , Soluções Cardioplégicas/farmacologia , Coração/efeitos dos fármacos , Hipotermia Induzida , Miocárdio/metabolismo , Inibidores de Serina Proteinase/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Trifosfato de Adenosina/metabolismo , Animais , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Óxido Nítrico/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Fator de Necrose Tumoral alfa/metabolismo
6.
J Thorac Cardiovasc Surg ; 111(2): 423-7; discussion 427-8, 1996 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8583816

RESUMO

Advanced age has traditionally been a contraindication to cardiac transplantation. We have, however, offered cardiac transplantation to patients older than 60 years with end-stage heart failure if they were otherwise acceptable candidates. From 1985 to 1994, 527 patients underwent cardiac transplantation. Among these patients, 101 were older than 60 years at transplantation. The mean follow-up of this group is 6 years. Patients older than 60 years had significantly fewer rejection episodes per patient than those who were younger than 60 years at transplantation (1.9 +/- 1.3 vs 2.6 +/- 1.8, p = 0.009). No difference in the number of infectious complications per patient was detected between the two groups. Both short-term and long-term survival after transplantation were significantly lower for patients who were older than 60 years at transplantation than for younger patients (p < 0.05). The 6-year actuarial survival after transplantation for patients older than 60 years was 54% compared with 72% for patients younger than 60 years at transplantation (p < 0.05). Patients older than 60 years at transplantation were more likely to die of infectious complications or malignant disease after transplantation (p < 0.05). We believe caution is warranted in offering cardiac transplantation to patients older than 60 years. This group of patients should be carefully observed for the development of potentially life-threatening infectious complications or new malignant tumors after transplantation.


Assuntos
Transplante de Coração , Fatores Etários , Contraindicações , Feminino , Rejeição de Enxerto , Transplante de Coração/imunologia , Transplante de Coração/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
7.
J Heart Lung Transplant ; 14(3): 424-8, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-7654726

RESUMO

BACKGROUND: The use of potentially infected donor hearts has been advocated to extend the supply of available hearts for transplantation. METHODS: To determine whether bacterial transmission from donor to recipient can occur with heart transplantation, we reviewed our experience with the 347 patients who received 360 heart transplants in the Utah Transplant Affiliated Hospitals from 1988 to 1993. RESULTS: During this time, nineteen donors had positive blood cultures before harvest. Sixteen donors had gram-positive bacteremia: Staphylococcus epidermidis (n = 9), Staphylococcus aureus (n = 5), streptococcus (n = 2). Two donors had gram-negative bacteremia: serratia (n = 1) and acinetobacter (n = 1). One donor had blood cultures positive for both Escherichia coli and streptococcus. Infectious complications occurred in two of three recipients who received a heart from a donor with gram-negative bacteremia: Escherichia coli endocarditis, mediastinitis, sepsis and death in one, and serratia sepsis and mediastinitis in another. In each case the organisms and sensitivities were identical between donor and recipient. No infectious complications related to the donor heart occurred among the 16 recipients who received hearts from donors with gram-positive bacteremia. CONCLUSIONS: (1) Bacterial transmission from donor heart to recipient can occur, (2) bacterial transmission appears to be more common with gram-negative organisms, and (3) infection of the recipient with a gram-negative organism from the donor heart is associated with significant morbidity and mortality.


Assuntos
Bacteriemia/microbiologia , Infecções Bacterianas/transmissão , Transplante de Coração , Doadores de Tecidos , Acinetobacter/isolamento & purificação , Adulto , Escherichia coli/isolamento & purificação , Infecções por Bactérias Gram-Negativas/transmissão , Humanos , Masculino , Pessoa de Meia-Idade , Serratia/isolamento & purificação , Staphylococcus aureus/isolamento & purificação , Staphylococcus epidermidis/isolamento & purificação , Streptococcus/isolamento & purificação
8.
J Heart Lung Transplant ; 18(2): 160-5, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10194040

RESUMO

BACKGROUND: Transfusion of cellular blood products during left ventricular assist device (LVAD) implantation has been associated with HLA allosensitization, resulting in the need for a negative prospective cross-match and prolonged transplant waiting times. In order to prevent this risk, we developed a protocol to avoid transfusion of cellular blood products. METHODS: The protocol included preoperative patient stabilization, perioperative recombinant erythropoietin and blood conservation strategies, and postoperative monitoring of mixed venous oxygen saturation (SVO2) to assure adequate peripheral oxygen delivery. Panel reactive antibody (PRA) was measured in all patients pre and post LVAD placement to assess HLA sensitization. RESULTS: Seven consecutive patients underwent LVAD implantation without transfusion of blood or platelets, one of whom expired perioperatively. Mean hematocrit was 35.2% preoperatively, and 21.8% postoperatively, reaching a nadir of 20.2%. Postoperative SVO2 was >60% in all patients. In the six survivors, mean hematocrit reach 24.3%, 27.3%, and 33.0% by postoperative day seven, fourteen, and thirty, respectively. PRA in three patients was 0% preoperatively and remained 0% until transplantation after 33, 34, and 50 days of support. In two patients, preoperative PRA was 7% and 17%, dropped to 3% and 0% after thirty days, then progressively rose to 96% and 100% after 60 and 90 days, respectively. In one other patient, preoperative PRA was 0%, remained at 0% after thirty days, then rose to 96% by 60 days. CONCLUSIONS: Avoiding transfusion of cellular blood products in LVAD recipients is safe and well tolerated, but does not universally protect from HLA allosensitization. Other factors may also produce sensitization, such as immunogenic components of the LVAD, soluble antigen in fresh frozen plasma, or latent sensitization which is not initially evident in critically ill and possibly anergic patients.


Assuntos
Antígenos HLA/imunologia , Coração Auxiliar , Isoanticorpos/sangue , Reação Transfusional , Adulto , Eritropoetina/administração & dosagem , Hematócrito , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Plasma , Cuidados Pós-Operatórios , Cuidados Pré-Operatórios , Estudos Prospectivos , Proteínas Recombinantes
9.
Ann Thorac Surg ; 71(1): 170-3; discussion 173-5, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11216740

RESUMO

BACKGROUND: Cardiopulmonary bypass (CPB) may contribute to the complications and cost of coronary artery bypass grafting (CABG). Off-pump CABG (OPCAB) allows coronary revascularization without CPB. We hypothesized that OPCAB provides satisfactory graft patency while reducing complications and cost compared with CABG with CPB. METHODS: We prospectively followed 80 patients undergoing CABG: 40 patients undergoing OPCAB and 40 patients undergoing CABG with CPB. OPCAB patients underwent angiography within 48 hours of surgery to determine early graft patency. Incidence of complications, length of stay, and costs were recorded for each patient. The influence of the number of vessels bypassed was analyzed. RESULTS: OPCAB patients (n = 40) underwent grafting of 2.7 +/- 0.7 vessels per patient compared with 3.6 +/- 0.8 vessels per patient in the CABG with CPB group (n = 40) (p < 0.0001). Angiography demonstrated 105 of 108 (97%) of grafts were patent in the OPCAB group. Incidence of complications, length of stay, and costs did not differ between the OPCAB and CABG with CPB groups. Number of vessels grafted showed a positive correlation to total costs in both groups. CONCLUSIONS: While OPCAB provided satisfactory early graft patency, there was no significant difference between OPCAB and CABG with CPB with regard to cost, length of stay, or incidence of complications. In this study, eliminating CPB did not reduce morbidity or cost after CABG.


Assuntos
Ponte Cardiopulmonar , Ponte de Artéria Coronária/métodos , Ponte Cardiopulmonar/economia , Ponte de Artéria Coronária/economia , Feminino , Custos Hospitalares , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Morbidade , Estudos Prospectivos , Resultado do Tratamento , Utah , Grau de Desobstrução Vascular
10.
Am J Surg ; 164(5): 512-6, 1992 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1443379

RESUMO

The effects on graft healing of alterations in the microstructure of polytetrafluoroethylene (PTFE) grafts induced by surgical instruments have not been fully elucidated. This study evaluates changes in the structural and physical properties of PTFE grafts resulting from the intentional application of commonly used surgical instruments and the influence of these changes on cellular ingrowth. The extent of cellular ingrowth into intact (10, 30, and 60 microns unreinforced and 30 microns reinforced [R]) and structurally compromised PTFE grafts (30 reinforced and 60 microns nonreinforced) implanted subcutaneously in Sprague-Dawley (n = 14) rats was evaluated at 7 and 21 days. The thrombogenicity of 10-, 30-, 60-, and 80-microns intact graft segments was determined gravimetrically after suspension in the internal jugular vein of dogs for 90 minutes. Cellular ingrowth consisting of fibroblasts, macrophages, and microvessels was directly related to porosity and was most extensive in 60-microns uncompromised graft segments, being 7-, 17-, and 20-fold greater than was observed in 60- and 30R-microns compromised grafts and undamaged 10-microns grafts, respectively. There was a direct relationship between porosity and thrombogenicity of intact graft segments suspended in the jugular vein. The amount of thrombus adherent to 80-microns graft segments was eightfold greater compared with 10-microns grafts. Manipulation of PTFE with surgical instruments significantly impairs healing and may be a possible etiologic factor in the poor long-term performance of these grafts.


Assuntos
Prótese Vascular , Vasos Sanguíneos/patologia , Politetrafluoretileno/química , Instrumentos Cirúrgicos , Trombose/etiologia , Animais , Cães , Elasticidade , Fibroblastos/patologia , Células Gigantes/patologia , Veias Jugulares/cirurgia , Macrófagos/patologia , Microscopia Eletrônica de Varredura , Porosidade , Ratos , Ratos Sprague-Dawley , Propriedades de Superfície , Trombose/patologia , Cicatrização
11.
Am J Surg ; 181(2): 142-4, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11425055

RESUMO

BACKGROUND: In this study we examine whether conversion from a didactic lecture format to a resident self-study and presentation program can improve performance on the Thoracic Surgery In-Training Examination (TSITE). METHODS: During the first 5 years, educational conferences were didactic lectures delivered by the attending thoracic surgery staff (group 1, n = 9 residents). During the second 5 years, residents prepared and delivered reviews from major textbook sources (group 2, n = 9 residents). Scores on the American Board of Surgery In-Training Examination (ABSITE) as a chief resident in general surgery were analyzed using one-way analysis of variance to assess fund of knowledge and test-taking skills prior to thoracic surgery training for the two groups. Scores on the TSITE during the first and second years of thoracic surgery training were recorded for each resident and analyzed using a paired t test. The data are expressed as the mean +/- standard deviation. RESULTS: Eighteen thoracic surgery residents over a 10-year period were involved in the study. ABSITE scores as a chief resident in general surgery did not differ between the two groups. Residents in group 1 improved their percentile rank from the first to the second year by a mean of 11%+/-12%, whereas those in group 2 improved their scores by a mean of 31%+/-21% (P < 0.05). CONCLUSIONS: When compared with a didactic lecture format, a resident self study and presentation program improves performance on the Thoracic Surgery In-Training Examination. This improvement in performance typically manifests during the second year of thoracic surgery training.


Assuntos
Avaliação Educacional , Internato e Residência/normas , Cirurgia Torácica/educação , Competência Clínica , Humanos , Avaliação de Programas e Projetos de Saúde , Ensino/métodos
12.
Am J Surg ; 180(6): 546-50, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11182415

RESUMO

BACKGROUND: Surgical resection of the larynx, hypopharynx and cervical esophagus, or pharyngolaryngoesophagectomy (PLE), with pharyngogastric anastomosis (PGA) offers a means of controlling local and regional carcinoma of the upper aerodigestive tract (UADT). We reviewed our experience with PLE for carcinoma of the UADT to evaluate functional outcome and survival. METHODS: Patients undergoing PLE from 1986 through 1999 were reviewed. Survivors completed questionnaires which graded their level of function and voice rehabilitation. Gastric emptying studies were performed with rates compared with normal controls. Survival curves were generated using the Kaplan-Meier method. RESULTS: Thirty-one patients underwent PLE during the study period. Twenty-nine patients had squamous cell carcinoma. Operative mortality was 0%. Thirty-day mortality was 9.6%. There were 2 anastomotic leaks (6.4%). All survivors reported normal ability to complete activities of daily living. Voice rehabilitation was acceptable in 7 of 10 survivors. Positive surgical margins resulted in decreased survival (P = 0.03). No other patient demographic or management variable altered survival. One-year, 5-year, and 10-year survival rates were 67%, 40%, and 18%, respectively. CONCLUSION: PLE with PGA for carcinoma of the UADT may be performed with low morbidity and mortality. Functional patient outcomes including gastric emptying, activities of daily living, and voice rehabilitation are acceptable.


Assuntos
Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/mortalidade , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/cirurgia , Idoso , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/cirurgia , Feminino , Esvaziamento Gástrico , Humanos , Neoplasias Hipofaríngeas/mortalidade , Neoplasias Hipofaríngeas/cirurgia , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sobrevida
13.
J Cardiovasc Surg (Torino) ; 32(5): 680-9, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1939333

RESUMO

Intraarterial urokinase (IAUK) was administered to 33 patients on 40 occasions for the treatment of acute extremity ischemia and long-term patency was assessed. Lysis was successful in 39 of the 40 cases (95%). Occlusive thrombus was cleared in 12 of 13 patients with native artery occlusion (7 complete, 5 partial), 8 of 9 with autologous vein grafts (5 complete, 3 partial), and in all 18 patients with synthetic grafts (17 complete, 1 partial). The primary cumulative patency following successful IAUK was 100% for native arteries and 47% for synthetic grafts at 12 months, and 23% for autologous grafts at 9 months. The difference in rethrombosis rate between autologous vein (67%) and native artery (0%) was significant (p = 0.02) as was the difference between infrainguinal prosthetic grafts (63%) and native artery (p = 0.025). IAUK is most effective for the treatment of native artery occlusion, but is significantly less effective for thrombosed infrainguinal autologous vein or synthetic grafts due to the likelihood of reocclusion, despite the high immediate success rate. For autologous vein grafts, lysis is frequently incomplete and patency rapidly deteriorates regardless of adjunctive therapy to relieve the underlying obstruction.


Assuntos
Prótese Vascular , Oclusão de Enxerto Vascular/tratamento farmacológico , Terapia Trombolítica , Trombose/tratamento farmacológico , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico , Feminino , Oclusão de Enxerto Vascular/epidemiologia , Humanos , Infusões Intra-Arteriais , Perna (Membro)/irrigação sanguínea , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Trombose/epidemiologia , Grau de Desobstrução Vascular
14.
J Cardiovasc Surg (Torino) ; 33(2): 172-7, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1533393

RESUMO

Atherosclerotic axillary artery aneurysms are rare. We report two cases of this entity and review the literature with respect to clinical presentation, diagnosis, operative management, and long-term outcome of these lesions.


Assuntos
Aneurisma/etiologia , Arteriosclerose/complicações , Artéria Axilar , Idoso , Aneurisma/diagnóstico , Aneurisma/patologia , Aneurisma/cirurgia , Arteriosclerose/patologia , Arteriosclerose/cirurgia , Prótese Vascular , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Polietilenotereftalatos
15.
J Cardiovasc Surg (Torino) ; 33(4): 401-6, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1527143

RESUMO

Patients presenting with symptoms suggestive of amaurosis fugax, or with findings of Hollenhorst plaques on fundoscopy are frequently referred for duplex evaluation to detect possible carotid artery disease. To better determine the reliability of monocular visual loss and the presence of Hollenhorst plaques for predicting the presence or significance of carotid artery stenosis, we prospectively studied 66 patients with these ocular signs and symptoms. After evaluation, the patients were categorized as follows: 34 of 66 (52%) patients had amaurosis fugax, 23 (35%) had asymptomatic Hollenhorst plaques, 7 (11%) had retinal artery occlusion, and 2 (3%) had venous stasis retinopathy. All patients were evaluated ophthalmologically, with carotid duplex scanning and spectral analysis. A stenosis of greater than 60% was regarded as significant. The presence of risk factors including hypertension, diabetes, a history of CVA or TIA's, tobacco use and hyperlipidemia was recorded. There were no statistically significant differences (p greater than 0.05) in the incidence of atherosclerotic risk factors between the four groups. Patients with amaurosis fugax were more likely to have a significant carotid artery stenosis than those with asymptomatic Hollenhorst plaques or retinal artery occlusion (53% vs 9% vs 0% respectively) (p less than 0.006). We conclude that routine carotid duplex scanning is indicated in all patients with amaurosis fugax in view of the frequent association with significant carotid stenosis (53%). However, the presence of Hollenhorst plaques in the absence of visual symptoms appears not to have a significant association with carotid disease and may not necessarily require routine screening unless other risk factors for carotid stenosis are present.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Estenose das Carótidas/diagnóstico , Oftalmopatias/diagnóstico , Idoso , Arizona/epidemiologia , Cegueira/diagnóstico , Cegueira/epidemiologia , Cegueira/etiologia , Estenose das Carótidas/complicações , Estenose das Carótidas/epidemiologia , Distribuição de Qui-Quadrado , Oftalmopatias/epidemiologia , Oftalmopatias/etiologia , Humanos , Incidência , Masculino , Estudos Prospectivos , Oclusão da Artéria Retiniana/diagnóstico , Oclusão da Artéria Retiniana/epidemiologia , Oclusão da Artéria Retiniana/etiologia , Doenças Retinianas/diagnóstico , Doenças Retinianas/epidemiologia , Doenças Retinianas/etiologia , Vasos Retinianos , Fatores de Risco
16.
Postgrad Med ; 89(2): 123-4, 126-8, 130, 1991 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-1990385

RESUMO

Patients with gallstone pancreatitis are often seen initially by primary care physicians. Prompt diagnosis and timely intervention are crucial in reducing morbidity and mortality. Initial management should include supportive medical care and surgical consultation. The timing of surgery is then dictated by serum enzyme levels and liver function test results as well as by the patient's condition. The role of endoscopic intervention is currently evolving. Whether surgery or endoscopic sphincterotomy is preferable as primary therapy for gallstone pancreatitis remains unresolved. However, sphincterotomy with stone extraction is a viable option in selected cases, especially in patients who have severe gallstone pancreatitis.


Assuntos
Colecistite/complicações , Pancreatite/etiologia , Adulto , Idoso , Colecistite/cirurgia , Feminino , Humanos
17.
Transplant Proc ; 42(7): 2687-92, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20832570

RESUMO

BACKGROUND: Blood product transfusion has been successfully used in solid-organ transplantation to induce tolerance. Whether a similar protective effect of blood product transfusion exists in heart transplantation is controversial. OBJECTIVE: To investigate the effect of cellular blood product transfusion within 2 weeks posttransplantation on the incidence of cellular and antibody-mediated rejection. PATIENTS AND METHODS: Patients were grouped on the basis of number of blood transfusions; group 1 received no transfusions, and groups 2, 3, and 4 each received an incremental number of transfusion units. All endomyocardial biopsy samples were routinely studied using immunofluorescence in the first 12 weeks posttransplantation. RESULTS: Baseline characteristics including age, sex, body mass index, history of diabetes, donor characteristics, and pretransplantation laboratory values were similar except that group 4 had a higher rate of previous sternotomy and longer ischemic time during transplantation. Approximately 9200 endomyocardial biopsy samples composed the data. Short- and long-term freedom from the International Society for Heart & Lung Transplantation grade 3A or higher cellular rejection and from antibody-mediated rejection were comparable between groups. CONCLUSIONS: Blood transfusions within the first 2 weeks post-transplantation do not seem to confer any protective effect against posttransplantation cellular rejection or antibody- mediated rejection. Whether other unmeasured confounding factors mask their effect requires further prospective studies.


Assuntos
Transfusão de Componentes Sanguíneos/métodos , Rejeição de Enxerto/prevenção & controle , Transplante de Coração/patologia , Tolerância Imunológica/efeitos dos fármacos , Adulto , Biópsia , Feminino , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/imunologia , Transplante de Coração-Pulmão/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento
19.
Gene Ther ; 10(7): 585-93, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12646864

RESUMO

Water-soluble lipopolymer (WSLP), which consisted of polyethylenimine (PEI, 1800 Da) and cholesterol, was characterized as a gene carrier to smooth muscle cells and myocardium. Acid-base titration showed that WSLP had a proton-buffering effect. The size of WSLP/plasmid DNA (pDNA) complex was around 70 nm. WSLP/pDNA complex was transfected to A7R5 cells, a smooth muscle cell line. WSLP showed the highest transfection at a 40/1 N/P ratio. WSLP has higher transfection efficiency than PEI (1800 and 25 000 Da), SuperFect, and lipofectamine. In addition, WSLP has less cytotoxicity than PEI (25 000 Da), SuperFect, and lipofectamine. Since WSLP has cholesterol moiety, it may utilize cellular cholesterol uptake pathway, in which low-density lipoprotein (LDL) is involved. An inhibition study with free cholesterol or low-density lipoprotein (LDL) showed that transfection was inhibited by cholesterol or LDL, suggesting that WSLP/pDNA complex is transfected to the cells through the cholesterol uptake pathway. To evaluate the transfection efficiency to myocardium, WSLP/pDNA complex was injected into the rabbit myocardium. WSLP showed higher transfection than PEI and naked pDNA. WSLP expressed the transgene for more than 2 weeks. In conclusion, WSLP is an efficient carrier for local gene transfection to myocardium, and useful in in vivo gene therapy.


Assuntos
Terapia Genética/métodos , Vetores Genéticos/genética , Miocárdio/metabolismo , Transfecção/métodos , Animais , Colesterol/genética , Expressão Gênica , Lipossomos , Luciferases/genética , Músculo Liso/metabolismo , Polietilenoimina , Coelhos
20.
Ann Surg ; 212(5): 561-6, 1990 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-2241311

RESUMO

The records of 145 paraplegic or quadriplegic patients were reviewed to identify those factors useful in the correct diagnosis of the acute abdomen in this population. Twenty-one patients had 22 episodes of acute or subacute abdominal problems. Presenting complaints, physical findings, and laboratory results were useful in various ways. However appropriate radiographic studies led to the correct diagnosis in 77% of patients. Although paraplegic and quadriplegic patients are predisposed to a distinct constellation of medical problems, including urinary tract infection and calculi, they also may present with other abdominal conditions that cause significant morbidity and mortality if not promptly recognized.


Assuntos
Abdome Agudo/etiologia , Paraplegia/complicações , Quadriplegia/complicações , Traumatismos da Medula Espinal/complicações , Abdome Agudo/diagnóstico por imagem , Adulto , Colecistite/complicações , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Úlcera Péptica Perfurada/complicações , Radiografia
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