RESUMO
We have localized transforming growth factor-beta (TGF-beta) in many cells and tissues with immunohistochemical methods, using two polyclonal antisera raised to different synthetic preparations of a peptide corresponding to the amino-terminal 30 amino acids of TGF-beta 1. These two antibodies give distinct staining patterns; the staining by anti-CC(1-30) is intracellular. This differential staining pattern is consistently observed in several systems, including cultured tumor cells; mouse embryonic, neonatal, and adult tissues; bovine fibropapillomas; and human colon carcinomas. The extracellular staining by anti-CC(1-30) partially resembles that seen with an antibody to fibronectin, suggesting that extracellular TGF-beta may be bound to matrix proteins. The intracellular staining by anti-LC(1-30) is similar to that seen with two other antibodies raised to peptides corresponding to either amino acids 266-278 of the TGF-beta 1 precursor sequence or to amino acids 50-75 of mature TGF-beta 1, suggesting that anti-LC(1-30) stains sites of TGF-beta synthesis. Results from RIA and ELISAs indicate that anti-LC(1-30) and anti-CC(1-30) recognize different epitopes of this peptide and of TGF-beta 1 itself.
Assuntos
Anticorpos/imunologia , Epitopos/imunologia , Imuno-Histoquímica , Fator de Necrose Tumoral alfa/análise , Animais , Bovinos , Neoplasias do Colo/análise , Ensaio de Imunoadsorção Enzimática , Matriz Extracelular/análise , Humanos , Técnicas de Imunoadsorção , Camundongos , Camundongos Nus , Papiloma/análise , Fragmentos de Peptídeos/imunologia , Precursores de Proteínas/imunologia , Radioimunoensaio , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/imunologiaRESUMO
The high incidence of fatal septicemia associated with severe thermal injury is believed to result from a loss of immunocompetence. To detect burn-mediated immune defects, lymphocyte function in peripheral blood leukocytes from 18 individuals sustaining 20-80% full thickness thermal burns was investigated. We examined the kinetics of the mitogen responses, the development of suppressive activity, and the correlation of mononuclear cell functional abnormalities with the incidence of sepsis. Patients were divided into three groups corresponding to their clinical course. The phytohemagglutinin responses of Ficoll-Hypaque purified leukocytes from eight of these patients (group III) were normal at day 1-2 after injury, but were significantly depressed (mean 16% of normal) at days 5-10 after injury. All of these group III patients experienced multiple, severe, septic episodes, and septic mortality was 75%. The other 10 burned individuals showed either augmented (group II) or unaltered (group I) mitogen responsiveness. Concomitant with evaluation of their mitogen responses, the cells of burn patients were assessed for development of suppressive activity by addition to on-going normal mixed leukocyte reactions (MLR). Only the addition of mononuclear cells with depressed phytohemagglutinin responsiveness (group III) significantly decreased MLR proliferation (mean 80% reduction) by the previously highly responsive, normal MLR combinations. Addition of cells from group III burn patients collected immediately after injury had no suppressive effect. Addition of cells from patients in group I or II or of normal individual's cells had no suppressive effect. These experimental results strongly suggest that a suppressive mononuclear cell is at least partially responsible for the decreased immunocompetence of burn patients.
Assuntos
Queimaduras/imunologia , Linfócitos T/imunologia , Adulto , Idoso , Feminino , Humanos , Terapia de Imunossupressão , Teste de Cultura Mista de Linfócitos , Masculino , Pessoa de Meia-Idade , Fito-Hemaglutininas/farmacologia , Fatores de TempoRESUMO
A 5' splice site located in a 3' untranslated region (3'UTR) has been shown previously to inhibit gene expression. Natural examples of inhibitory 5' splice sites have been identified in the late 3'UTRs of papillomaviruses and are thought to inhibit viral late gene expression at early stages of the viral life cycle. In this study, we demonstrate that the interaction of the human immunodeficiency virus type 1 Rev protein with the Rev-responsive element (RRE) overcomes the inhibitory effects of a 5' splice site located within a 3'UTR. This was studied by using both a bovine papillomavirus type 1 L1 cDNA expression vector and a chloramphenicol acetyltransferase expression vector containing a 5' splice site in the 3'UTR. In both systems, coexpression of Rev enhanced cytoplasmic expression from vectors containing the RRE even when the RRE and the inhibitory 5' splice site were separated by up to 1,000 nucleotides. In addition, multiple copies of a 5' splice site in a 3'UTR were shown to act synergistically, and this effect could also be moderated by the interaction of Rev and the RRE. These studies provide additional evidence that at least one mechanism of Rev action is through interactions with the splicing machinery. We have previously shown that base pairing between the U1 small nuclear RNA and a 3'UTR 5' splice site is required for inhibition of gene expression. However, experiments by J. Kjems and P. A. Sharp (J. Virol. 67:4769-4776, 1993) have suggested that Rev acts on spliceosome assembly at a stage after binding of the U1 small nuclear ribonucleoprotein to the 5' splice site. This finding suggests that binding of additional small nuclear ribonucleoproteins, as well as other splicing factors, may be necessary for the inhibitory action of a 3'UTR 5' splice site. These data also suggest that expression of the papillomavirus late genes in terminally differentiated keratinocytes can be regulated by a viral or cellular Rev-like activity.
Assuntos
Produtos do Gene rev/genética , Genes env/genética , HIV-1/genética , Sequência de Bases , DNA Complementar/análise , Regulação Viral da Expressão Gênica , Produtos do Gene rev/metabolismo , HIV-1/metabolismo , Células HeLa , Humanos , Dados de Sequência Molecular , Splicing de RNA , RNA Viral/genética , RNA Viral/metabolismo , Produtos do Gene rev do Vírus da Imunodeficiência HumanaRESUMO
Expression of bovine papillomavirus type 1 (BPV-1) late genes is limited to terminally differentiated keratinocytes in an infected epithelium. We have previously shown that although the BPV-1 late polyadenylation site is functional in nonpermissive cells, a 53-nucleotide (nt) fragment of the late 3' untranslated region acts posttranscriptionally to reduce polyadenylated cytoplasmic RNA levels. This 53-nt fragment does not appear to function by destabilizing polyadenylated cytoplasmic RNA (P. A. Furth and C. C. Baker, J. Virol. 65:5806-5812, 1991). In this study, we used site-directed mutagenesis and deletion analysis to demonstrate that the sequence AAG/GUAAGU, which is identical to the consensus 5' splice site sequence, was both necessary and sufficient for the inhibitory activity of the 53-nt fragment. Furthermore, base pairing between the 5' end of the U1 small nuclear RNA and this 5' splice site-like sequence was shown to be required for the inhibitory activity in vivo. We have also further mapped the human papillomavirus type 16 late 3' inhibitory element (I. M. Kennedy, J. K. Haddow, and J. B. Clements, J. Virol. 65:2093-2097, 1991) to a 51-nt region containing four overlapping sequence motifs with partial homology to 5' splice sites. Mutation of each of these motifs demonstrated that only one of these motifs is required for the inhibitory activity. However, the presence of the other motifs may contribute to the full inhibitory activity of the element. No BPV-1 or human papillomavirus type 16 mRNAs which are spliced by using the potential 5' splice sites present in the viral late 3' untranslated regions have been identified. This suggests that the primary function of these 5' splice site-like sequences is the inhibition of late gene expression. The most likely mechanism of action of these elements is reduction of polyadenylation efficiency, perhaps through interference with 3'-terminal exon definition.
Assuntos
Papillomavirus Bovino 1/genética , Regulação Viral da Expressão Gênica , RNA Mensageiro/genética , Sequência de Bases , Sequência Consenso , Ligação de Hidrogênio , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Papillomaviridae/genética , Poli A/metabolismo , Processamento Pós-Transcricional do RNA , Splicing de RNA , RNA Nuclear Pequeno/genética , RNA Viral/genética , Sequências Reguladoras de Ácido Nucleico , Relação Estrutura-AtividadeRESUMO
Genomic imprinting is an epigenetic process that results in the preferential silencing of one of the two parental copies of a gene. Although the precise mechanisms by which genomic imprinting occurs are unknown, the tendency of imprinted genes to exist in chromosomal clusters suggests long-range regulation through shared regulatory elements. We characterize a 800-kb region on the distal end of mouse chromosome 7 that contains a cluster of four maternally expressed genes, H19, Mash2, Kvlqt1, and p57(Kip2), as well as two paternally expressed genes, Igf2 and Ins2, and assess the expression and imprinting of Mash2, Kvlqt1, and p57(Kip2) during development in embryonic and extraembryonic tissues. Unlike Igf2 and Ins2, which depend on H19 for their imprinting, Mash2, p57(Kip2), and Kvlqt1 are unaffected by a deletion of the H19 gene region, suggesting that these more telomeric genes are not regulated by the mechanism that controls H19, Igf2, and Ins2. Mutations in human p57(Kip2) have been implicated in Beckwith-Wiedemann syndrome, a disease that has also been associated with loss of imprinting of IGF2. We find, however, that a deletion of the gene has no effect on imprinting within the cluster. Surprisingly, the three maternally expressed genes are regulated very differently by DNA methylation; p57(Kip2) is activated, Kvlqt1 is silenced, and Mash2 is unaffected in mice lacking DNA methyltransferase. We conclude that H19 is not a global regulator of imprinting on distal chromosome 7 and that the telomeric genes are imprinted by a separate mechanism(s).
Assuntos
Cromossomos , Impressão Genômica , Canais de Potássio de Abertura Dependente da Tensão da Membrana , RNA não Traduzido , Fatores de Transcrição , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Mapeamento Cromossômico , Inibidor de Quinase Dependente de Ciclina p57 , Metilação de DNA , Metilases de Modificação do DNA/genética , Proteínas de Ligação a DNA/genética , Deleção de Genes , Genes Supressores de Tumor , Ligação Genética , Humanos , Fator de Crescimento Insulin-Like II/genética , Canais de Potássio KCNQ , Canal de Potássio KCNQ1 , Camundongos , Proteínas Musculares/genética , Mutagênese Sítio-Dirigida , Proteínas Nucleares/genética , Canais de Potássio/genética , Proinsulina/genética , RNA Longo não CodificanteRESUMO
A novel method combining elemental sulfur and selenium was developed, yielding crystalline sulfur-selenium compounds. The compounds were melted, and an organic comonomer added. Once the organic comonomer was consumed, the viscous compound was vitrified and allowed to cool yielding organic-inorganic hybrid polymers that are termed Organically Modified Chalcogenide (ORMOCHALC) polymers.
RESUMO
Transforming growth factor-beta 1 (TGF beta 1) has been purified from a number of different sources and has a broad species specificity. To deduce the complete amino acid sequence of bovine TGF beta 1 we have isolated cDNA clones encoding the protein from a bovine fibropapilloma library using a human cDNA probe. Sequence analysis of two independent cDNA clones revealed that the 112 amino acids corresponding to bovine TGF beta 1 are identical to those of the human and porcine proteins. This unusually high degree of conservation in the primary structure of the human and bovine proteins reflects the strong evolutionary constraints for maintenance of structure and function of the molecule. As in the human, murine, and porcine systems, the mature form of TGF beta 1 is derived by proteolytic cleavage of a larger precursor. Small differences in amino acid sequence were observed in the portion of the precursor that does not include mature TGF beta 1, although 92% of the residues are still conserved. A 2.25 kilobase (kb) mRNA was identified in total bovine wart and bone RNA, whereas no message was detected in polyadenylated spleen or brain RNA. In addition to the major 2.25 kb message, we observed a 1.9 kb transcript in poly(A+) RNA from wart tissue.
Assuntos
Fator de Crescimento Transformador beta/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Northern Blotting , Bovinos , Clonagem Molecular , DNA/genética , DNA/isolamento & purificação , Dados de Sequência Molecular , RNA Mensageiro/biossíntese , Homologia de Sequência do Ácido Nucleico , Especificidade da EspécieRESUMO
BACKGROUND: Sumatriptan nasal spray may be particularly useful for patients whose nausea and vomiting preclude them from using oral migraine medication or for patients who prefer not to use an injectable migraine medication. The objective of this study was to evaluate in two clinical studies the efficacy and tolerability of the intranasal form of sumatriptan in the acute treatment of a single migraine attack. International Headache Society-diagnosed adult migraineurs in two randomized, double-blind, parallel-group, multicenter studies (n = 409 and 436) used sumatriptan nasal spray 20 mg, 10 mg, or placebo (2:1:1) for the acute treatment of a single migraine attack at home. Predose and at predetermined postdose intervals, patients recorded headache severity (none, mild, moderate, severe); time to meaningful relief; clinical disability (none, mildly impaired, severely impaired, bed rest required); presence/absence of nausea, photophobia, and phonophobia; and the occurrence of adverse events. Two hours postdose in the two studies, moderate or severe baseline pain was reduced to mild or none in 62 to 63% of patients treated with sumatriptan 20 mg, 43 to 54% of patients treated with sumatriptan 10 mg, and 29 to 35% of placebo-treated patients (p < 0.05 20 mg versus placebo for both studies and 10 mg versus placebo for study 1). Onset of relief relative to placebo began as early as 15 minutes postdose (sumatriptan 20 mg, study 2). Clinical disability at 2 hours postdose was reported as mildly impaired or normal in 72 to 74% of patients treated with sumatriptan 20 mg, 56 to 68% of patients treated with sumatriptan 10 mg, and 47 to 58% of placebo-treated patients (p < 0.05 20 mg versus placebo for both studies). Similar efficacy rates were observed for nausea, photophobia, and phonophobia. The most common adverse event in the active treatment groups was disturbance of taste (bad, bitter, or unpleasant taste). Aside from this event, the pattern and incidence of adverse events did not differ among treatment groups. From these results we determined that sumatriptan nasal spray is a rapidly effective, well-tolerated migraine treatment. The 20-mg dose was effective in treating the entire migraine symptom complex, and the 10-mg dose was less consistently effective.
Assuntos
Transtornos de Enxaqueca/tratamento farmacológico , Agonistas do Receptor de Serotonina/administração & dosagem , Sumatriptana/administração & dosagem , Doença Aguda , Administração Intranasal , Adolescente , Adulto , Idoso , Avaliação da Deficiência , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Agonistas do Receptor de Serotonina/efeitos adversos , Sumatriptana/efeitos adversosRESUMO
Hemorrhagic shock appears to predispose patients to subsequent sepsis. This study examined the effect of different resuscitation fluids on macrophage function following hemorrhagic shock. Male Sprague-Dawley rats were bled to a blood pressure of 50 mmHg for 60 min and then resuscitated with 6% hydroxyethyl starch (HES) or Lactated Ringers (LR). Phagocytic function was assessed by clearance of IV colloidal carbon (C). Carbon clearance was not statistically different between control (154.89), shock LR (169.16), and shock HES (144.60). Computerized image analysis of C distribution in sections of liver and spleen taken 4 h after C infusion exhibits a significant decrease in C distribution after resuscitation with HES compared to control and animals resuscitated with LR (Student's t test, p < .05). Male CBA/J mice were bled to a mean blood pressure of 50 mmHg for 60 min and then resuscitated with either LR (N = 18) or HES (N = 17). In separate experiments CBA/J mice had no shock, but were given LR or HES followed by cecal ligation and puncture and later excision (CLPE). A final group had shock with either LR or HES resuscitation and then CLPE as above. Splenocytes were harvested 48 h after shock for mixed lymphocyte culture (MLC). Animals undergoing shock with subsequent septic challenge (Shock/CLPE) showed significantly increased mortality 40 vs. 0% (chi square, p < .05) and immunosuppression on MLC 2,088(LR)/3,300 (HES) vs. 18,570 (LR)/17,705 (HES) compared to CLPE alone (Student's t test, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Derivados de Hidroxietil Amido/farmacologia , Soluções Isotônicas/farmacologia , Linfócitos/imunologia , Macrófagos/fisiologia , Ressuscitação , Sepse/fisiopatologia , Choque Hemorrágico/fisiopatologia , Animais , Pressão Sanguínea , Ceco , Teste de Cultura Mista de Linfócitos , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos CBA , Ratos , Ratos Sprague-Dawley , Lactato de Ringer , Sepse/imunologia , Choque Hemorrágico/imunologiaRESUMO
This study examined effects of trauma and sepsis on Kupffer cell function. When CBA/J mice had femur fracture (FFx), no deaths occurred. After cecal ligation and puncture (CLP), 44% died. Following combined injuries (FFx + CLP), mortality increased to 60%, suggesting a deleterious effect between FFx + CLP. Kupffer cell ablation with GdCI3 decreased mortality to 13% after CLP and 5% after FFx + CLP. After FFx, CLP, and FFx + CLP, Kupffer cells isolated from Sprague-Dawley rats produced 720%, 1,100%, and 2,130% more O2. than sham, respectively. Phagocytosis increased 320%, 610%, and 150%. Kupffer cell PGE2 production also increased 300%, 510%, and 300% over sham. After FFx alone, TNF-alpha production decreased 40%. By contrast, CLP and FFx + CLP increased TNF-alpha release 25% and 100%, respectively. After FFx, NO. production decreased 44%, whereas NO increased 280% and 260% after CLP and FFx + CLP. These findings indicate that Kupffer cells mediate mortality after CLP and FFx + CLP. Increased mortality is associated with a more proinflammatory and less antimicrobial Kupffer cell phenotype.
Assuntos
Fraturas do Fêmur/fisiopatologia , Células de Kupffer/fisiologia , Sepse/fisiopatologia , Animais , Ceco/microbiologia , Células Cultivadas , Dinoprostona/metabolismo , Endotoxinas/toxicidade , Escherichia coli , Fraturas do Fêmur/complicações , Células de Kupffer/efeitos dos fármacos , Células de Kupffer/patologia , Lipopolissacarídeos/toxicidade , Camundongos , Camundongos Endogâmicos DBA , Óxido Nítrico/fisiologia , Fagocitose , Ratos , Ratos Sprague-Dawley , Sepse/etiologia , Superóxidos/metabolismo , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Alterations in intestinal permeability and immune function were investigated in a murine femur fracture (FFx) model. We postulated that soft tissue injury associated with closed FFx (crush injury) would result in greater immunosuppression that open FFx (surgical division). AKR mice were randomized to four groups (Normal, Sham, Open FFx, Closed FFx) and studied at 24 and 96 h post-injury. Immune function was assessed by splenocyte blastogenic response and class-specific immunoglobulin production. Intestinal permeability was assessed by measurement of whole blood fluorometry after gavage administration of fluorescein-dextran (FITC-dextran). Closed FFx is associated with increased splenocyte blastogenesis and increased immunoglobulin production at 24 h post-injury. This immunostimulatory response was associated with altered intestinal permeability early after injury (FITC-dextran:.185 +/- .070 Closed FFx vs. .069 +/- .011 Normal, p = .06). Immunosuppression was evident at 96 h post-injury in the closed FFx group, documented by significant reductions in splenocyte blastogenesis to all mitogens studied. The Open FFx group did not demonstrate any reduction in splenocyte blastogenesis at 96 h post-injury. These data suggest that the soft tissue injury associated with Closed FFx is associated with significant immunosuppression and altered gastrointestinal permeability, which may adversely affect the host by increasing the relative risk of post-trauma infection.
Assuntos
Fraturas do Fêmur/fisiopatologia , Tolerância Imunológica , Absorção Intestinal/fisiologia , Lesões dos Tecidos Moles/etiologia , Animais , Peso Corporal/fisiologia , Fraturas do Fêmur/complicações , Fraturas do Fêmur/imunologia , Imunoglobulinas/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos AKR , Mitógenos/farmacologia , Permeabilidade , Distribuição Aleatória , Baço/citologia , Baço/efeitos dos fármacosRESUMO
Functional changes in Kupffer cells occur after profound hemorrhagic shock. This study was performed to demonstrate if Kupffer cell changes also occur after mild hemorrhagic shock. Sprague-Dawley rats were bled to a systolic blood pressure of 60 to 70 mmHg and resuscitated with Lactated Ringers solution (twice the shed blood volume) after 30 min. Resuscitation produced immediate recovery of blood pressure and allowed long-term recovery of the animals. Sham animals received anesthesia and monitoring only. Thirty minutes after resuscitation, Kupffer cells were isolated by centrifugal elutriation and cultured for 48 h. In Kupffer cells isolated from shocked animals, phorbol ester-stimulated superoxide production increased 7-fold and lipopolysaccharide- (LPS) stimulated prostaglandin E2 (PGE2) production increased 4-fold. Tumor necrosis factor-alpha (TNFalpha) production, on the other hand, was decreased by 50%. A non-significant trend toward increased phagocytosis was also observed, whereas LPS-stimulated nitric oxide production was unchanged. In conclusion, mild hemorrhagic shock produced increases in superoxide and PGE2 production, and decreases in TNFalpha production by Kupffer cells, changes that may be appropriate to defend against the infectious challenges that often follows trauma and hemorrhage.
Assuntos
Células de Kupffer/fisiologia , Choque Hemorrágico/fisiopatologia , Animais , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
In the setting of rapidly exsanguinating hemorrhage, resuscitation with intravenous (i.v.) crystalloid solution may not sustain survival before availability of allogenic blood transfusion and surgery. This study tested the hypothesis that bovine hemoglobin-based oxygen carrier, HBOC-201, would improve resuscitation and extend early survival from exsanguinating hemorrhage. This study simulated the prehospital scenario of rapidly exsanguinating hemorrhage with prolonged prehospital time and lack of blood availability. Severe hemorrhagic shock was induced in swine by using multiple liver lacerations. At 9 min after the onset of bleeding, swine were randomized to receive approximately 10 mL/kg/min of i.v. lactated Ringer's solution (n = 10) or HBOC-201 (n = 7) to achieve a mean aortic pressure (MAP) of 60 mmHg. Thereafter, infusion rate was adjusted to maintain MAP at 60 mmHg for up to 2 h. All animals were initially successfully resuscitated. The results showed 2-h survival was 1 of 10 with lactated Ringer's and 7 of 7 with HBOC-201 (P = 0.0004). Nine lactated Ringer's swine had cardiovascular collapse at 36 +/- 10 min. Lactate at 30 min was 18 +/- 3 mmol/L with lactated Ringer's and 12 +/- 2 mmol/L with HBOC-201 (P < 0.05). Hematocrit was <1% in 9 of 10 lactated Ringer's and 6 of 7 HBOC-201 animals. These data indicate that HBOC-201 improved early survival and stabilized hemodynamic and metabolic parameters vs. lactated Ringer's in this swine model of liver injury with uncontrolled, lethal hemorrhage that simulates the prehospital care environment where allogenic blood is unavailable.
Assuntos
Substitutos Sanguíneos/administração & dosagem , Hemodinâmica/efeitos dos fármacos , Hemorragia/terapia , Fígado/lesões , Ressuscitação/métodos , Ferimentos Penetrantes/terapia , Animais , Gasometria , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Hematócrito , Hemoglobinas , Hemorragia/fisiopatologia , Infusões Intravenosas , Soluções Isotônicas/administração & dosagem , Ácido Láctico/sangue , Fígado/irrigação sanguínea , Distribuição Aleatória , Respiração/efeitos dos fármacos , Solução de Ringer , Taxa de Sobrevida , Suínos , Ferimentos Penetrantes/fisiopatologiaRESUMO
One hundred eighty-one patients with 218 acute cervicothoracic vascular injuries underwent operations for diagnosis, resuscitation, and control of hemorrhage. The patients were divided into three clinical groups depending on their clinical status. Group I consisted of 105 patients who were hemodynamically stable and able to undergo diagnostic measures: Group II consisted of 41 patients who remained unstable and required immediate operation; Group III consisted of 35 patients who were moribund and underwent emergency room thoracotomy. The mortality rates were 4% for Group I, 15% for Group II, and 80% for Group III with an overall mortality rate of 21%. Angiography was performed in 53% of the stable Group I patients. This allowed specific identification of lesions such as arteriovenous fistula in eight patients and aortic disruption in 12 patients. Thirty-five Group III patients had thoracotomy performed in the emergency room and seven survived (20%). A vigorous clinical approach is recommended to minimize morbidity. A different approach is described for each of the three clinical groups of patients.
Assuntos
Pescoço/irrigação sanguínea , Tórax/irrigação sanguínea , Ferimentos por Arma de Fogo/cirurgia , Ferimentos não Penetrantes/cirurgia , Ferimentos Perfurantes/cirurgia , Adolescente , Adulto , Idoso , Emergências , Feminino , Hemodinâmica , Humanos , Pulmão/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Cirurgia Torácica , Ferimentos por Arma de Fogo/mortalidade , Ferimentos não Penetrantes/mortalidade , Ferimentos Perfurantes/mortalidadeRESUMO
It has been suggested that interleukin 1 (IL-1) may be elevated systemically after major burn injury. Several metabolic changes commonly observed in patients with burns can be attributed in part to elevated IL-1 production; these include temperature elevation, skeletal muscle proteolysis, and alterations in the production of certain serum proteins by the hepatocyte (e.g., albumin and acute phase reactants). In this article we describe a likely source of this elevated IL-1 activity: the burn wound. Fluid taken from blisters on thermally injured skin early after burn injury contains substantial amounts of IL-1. This activity is less apparent in certain blister fluid (BF) samples, probably because of the presence of an inhibitor(s) of lymphocyte proliferation. However, after gel filtration high-performance liquid chromatography, the IL-1 actively elutes at a molecular weight of 15,000 to 20,000 daltons and can be blocked with an antibody to IL-1. We suggest that the source of this IL-1 activity is the injured keratinocyte and that release of this IL-1 systemically is inevitable. We postulate that release of IL-1 from the wound into the systemic circulation accounts in part for the metabolic changes outlined above. Furthermore, since epidermal IL-1 is a potent T cell chemoattractant, we believe that burn wound IL-1 may affect sequestration of T cells near the burn wound, resulting in T cell lymphopenia.
Assuntos
Queimaduras/metabolismo , Interleucina-1/biossíntese , Vesícula/metabolismo , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Exsudatos e Transudatos/análise , Humanos , Pele/citologia , Pele/metabolismo , Fatores de TempoRESUMO
T helper (Th) cell dysfunction occurring very early (i.e., 24 to 72 hours) after a 30% full-thickness burn in a murine model cannot be attributed to suppressor T cell activity. Th cell activity is influenced by the activity of antigen-presenting cells (APCs). These cells process antigen and present a complex of antigen and cell surface Ia to the T cell. Additionally, they elaborate interleukin-1 (Il-1), and these events lead to Th cell release of Il-2, expression of Il-2 receptors, and proliferation of Th cells. We examined the contribution of APCs to postburn Th cell dysfunction by using mitomycin C-treated spleen cells from normal and burned mice as an APC population. The Th cell population consisted of a cloned Th cell line (D10.G4.1) that recognizes conalbumin in the context of I-Ak and proliferates when approximately stimulated. We found that APCs from burned mice induced significantly less Th cell proliferation (p less than 0.05). This was true of unfractionated spleen cells (50.4% of control) as well as positively selected (44.2% of control) or negatively selected (51.9% of control) splenic APCs. When cocultured with APCs from control mice, APCs from burned mice did not suppress control values of Th cell proliferation. Finally, the addition of murine Il-1 in vitro to cultures of burn-derived APCs, antigen, and T cell clone restored Th cell proliferation to control levels (from 38.3% to 92.8%) without nonspecifically enhancing similar cultures employing normal APCs. Il-1 in vitro did not improve Th cell function in the absence of antigen. Thus splenic APCs from mice exhibit defective antigen presentation early after burn injury. This defect is not a result of suppressor factor production by burn APCs and can be restored by Il-1 in vitro. Th cell dysfunction early after burn injury is thus due, in part, to APC dysfunction.
Assuntos
Células Apresentadoras de Antígenos/imunologia , Queimaduras/imunologia , Interleucina-1/fisiologia , Macrófagos/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Células Clonais/imunologia , Modelos Animais de Doenças , Síndromes de Imunodeficiência/terapia , Ativação Linfocitária , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos CBA , Fenótipo , Baço/citologia , Baço/imunologia , Linfócitos T Auxiliares-Indutores/classificação , Linfócitos T Reguladores/imunologiaRESUMO
A murine model was used to test the effects of various therapeutic modalities on the rate of death following intra-abdominal sepsis as produced by cecal ligation and puncture (CLP). There were no deaths among sham-operated control mice after ether anesthesia, whereas CLP produced a mortality rate of 100% by 24 hours. When CLP was followed at 16 hours by excision of the cecum and saline peritoneal lavage (CLPE), the mortality rate was 20% at 24 hours and 60% at 72 hours. The therapeutic modalities consisted of gentamicin (1.5 mg/kg) alone or in combination with methylprednisolone (50 mg/kg) or tuftsin (1 mg/kg) administered before CLP and at 16 and 24 hours after CLP. Separate groups of animals also received only methylprednisolone or tuftsin, a tetrapeptide produced by the spleen. Compared with the mortality rate in the CLPE group, mortality at 24 and 72 hours was decreased for gentamicin alone (0% and 10%, respectively), tuftsin alone (10%, 40%), or the two in combination (0%, 20%). As compared with CLPE, methylprednisolone led to increased mortality rates at 24 and 72 hours (70%, 80%). The data (significant at P less than 0.01, X2 analysis) suggest that gentamicin and tuftsin may improve the rate of early survival after intra-abdominal sepsis in this Model. Steroids do not seem to be beneficial and may, in fact, be harmful.
Assuntos
Antibacterianos/administração & dosagem , Infecções Bacterianas/mortalidade , Ceco/cirurgia , Modelos Animais de Doenças , Pré-Medicação , Anestesia/mortalidade , Animais , Infecções Bacterianas/tratamento farmacológico , Quimioterapia Combinada , Éter , Estudos de Avaliação como Assunto , Feminino , Ligadura , Masculino , Camundongos , Camundongos Endogâmicos DBA , Punções , Irrigação Terapêutica , Fatores de TempoRESUMO
BACKGROUND: Accurate data are needed to evaluate outcomes, therapeutics, and quality of care. This study assesses the accuracy of administrative databases in recording information about trauma patients. METHODS: Patients with thoracic aorta injury were identified with a state trauma registry, and the medical records were reviewed. Data collected were compared to administrative data on patients with thoracic aorta injuries, at the same hospitals in the same time period. RESULTS: Fifteen patients (16.3%) with thoracic aorta injury were not recorded in the administrative database, and 23 patients (18.7%) were misdiagnosed. Ninety-one patients were found in both data sources. The administrative database significantly (P < .05) underrecorded abdominal injuries (50 vs 35), orthopedic injuries (117 vs 75), and chest injuries (77 vs 48). The number of aortograms (78 vs 8), type of operative procedures (use of graft; 70 vs 30), use of bypass (35 vs 16), and complications (77 vs 33) were underreported (P < .05). The Injury Severity Score was underestimated by the administrative database (38.65 +/- 12.41 vs 25.66 +/- 9.53; P < .05). CONCLUSIONS: Administrative data lack accuracy in the recording of associated injury, injury severity, diagnostic, and procedural data. Whether these data should be used to evaluate treatment or quality of care in trauma is questionable.
Assuntos
Aorta Torácica/lesões , Bases de Dados como Assunto , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de RegistrosRESUMO
Cystoid macular edema after cataract surgery, with or without intraocular lens implantation, has been reported to develop in more than 50% of patients as detected by fluorescein angiography. It is associated with reduced visual acuity in up to 8% of cases. Analysis of ongoing clinical trials at the Wilmer Institute indicates that clinically significant cystoid macular edema develops in a lower percentage of cases (2% total incidence and 0.3% persistent cystoid macular edema) if the intraocular lens implantation was uncomplicated. The factors associated with cystoid macular edema and the importance of considering clinically significant rather than just fluorescein-proven cystoid macular edema are discussed. Results of intraocular lens studies reported to the Federal Drug Administration are updated, and results of an ongoing study of prostaglandin inhibitors at the Wilmer Institute are reported.
Assuntos
Lentes Intraoculares/efeitos adversos , Edema Macular/etiologia , Idoso , Extração de Catarata/métodos , Avaliação de Medicamentos , Angiofluoresceinografia , Seguimentos , Humanos , Edema Macular/diagnóstico , Edema Macular/epidemiologia , Edema Macular/prevenção & controle , Pessoa de Meia-Idade , Estudos Prospectivos , Antagonistas de Prostaglandina/uso terapêutico , Suprofeno/uso terapêuticoRESUMO
Sixty-four patients with cardiac contusion documented by electrocardiographic changes and creatine kinase MB fraction assay following blunt chest injury were reviewed to assess the impact of cardiac contusion on subsequent management. Fifty-eight patients had elevated creatine kinase MB levels; 35 patients had electrocardiographic abnormalities, including ST-segment and T-wave changes (25), premature ventricular contraction (ten), right bundle-branch block (nine), atrioventricular block (three), atrial fibrillation (three), and premature atrial contraction (two). Thirty patients underwent general anesthesia. There were only four perioperative complications: ventricular ectopy, ventricular fibrillation, nodal rhythm, and pulmonary edema. There were no deaths attributable to cardiac contusion. In summary, patients with blunt trauma who have sustained a cardiac contusion can undergo elective operation with a low incidence of complication. In the emergency setting, however, hemodynamic monitoring for early detection of arrhythmias is indicated.