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1.
Zentralbl Chir ; 138(2): 144-50, 2013 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-22392262

RESUMO

BACKGROUND: According to the approval system for medical doctors, practical courses such as block practical training must be graded. The grading of the surgical block practical training at the Klinikum rechts der Isar, Technische Universität of Munich (TUM), was changed from single grades of each day to a final objective structured clinical examination (OSCE). We report about the experiences in the past 12 months with this relatively new form of examination. METHODS: An OSCE was established as a practical exam with seven stations about suture techniques, internal fixation, first-aid education, hygiene and sterility, clinical examination and perioperative management. The feasibility of a comprehensive OSCE with the necessary modifications was studied and the grades had been compared. RESULTS: In the past 12 months four surgical block placements for over three weeks had been organised with a total of 326 students. 309 students were admitted for the OSCE at the end of block practical training. The average score was 1.75. The medical student raters graded either equally or more stringently compared to the medical doctors. The transcript revealed in all OSCEs a normal distribution of grading with high validity. However, an adaptation of the evaluation forms and an extension of the stations with modified content was required to obtain the same test conditions for all students. The implementation of the OSCE on this scale is possible with adequate preparation time and sufficient financial support. The evaluation of the specimens after completion of the test were all positive. CONCLUSION: The new medical approval system calls for restructuring, not only in teaching but also in the form of examination of the courses. Through this practical test, those skills of a student will be assessed that cannot be tested by the IMPP exam. Moreover, this examination form provides an excellent preparation for the practical part of the oral state examination. This OSCE is even feasible with high numbers of students and offers with appropriate adaptation of the evaluation forms and test stations, a normal distribution of grading.


Assuntos
Educação de Pós-Graduação em Medicina/normas , Avaliação Educacional/normas , Cirurgia Geral/educação , Internato e Residência/normas , Conselhos de Especialidade Profissional/normas , Competência Clínica/normas , Currículo/normas , Estudos de Viabilidade , Alemanha , Hospitais Universitários , Humanos
2.
Transplant Proc ; 42(5): 1523-5, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20620467

RESUMO

Delayed graft function (DGF) has one of the greatest effects on short- and long-term outcomes of cadaveric renal allografts. Ischemia reperfusion injury in the context of cold ischemia time and acute calcineurin inhibitor (CNI) nephrotoxicity is a major factor predisposing to DGF. A drug regimen consisting of prostaglandin E(1) (PGE(1)) furosemide and dopamine has been used to reduce DGF after kidney transplantation. Prostaglandin E(1) has multiple anti-ischemic and tissue-protective abilities, furosemide improves diuresis, and dopamine augments renal blood flow and urinary volume. To evaluate a potential positive effect of this drug regimen on the primary function of cadaveric renal allografts, we performed a retrospective single-center study that compared 100 patients who received this regimen with a control group. The results showed no significant improvement in renal function. In contrast, plasma levels of creatinine and urea were increased in the drug regimen group. Thus, the effectiveness of PGE(1) in combination with high-dose furosemide and dopamine in diminishing DGF was not demonstrated in this trial.


Assuntos
Alprostadil/uso terapêutico , Dopamina/uso terapêutico , Furosemida/uso terapêutico , Transplante de Rim/fisiologia , Adulto , Alprostadil/administração & dosagem , Cadáver , Diuréticos/administração & dosagem , Diuréticos/uso terapêutico , Dopamina/administração & dosagem , Feminino , Furosemida/administração & dosagem , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/prevenção & controle , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Diálise Renal/estatística & dados numéricos , Estudos Retrospectivos , Doadores de Tecidos , Transplante Homólogo
3.
Zentralbl Chir ; 135(1): 18-24, 2010 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-20162500

RESUMO

The shortage of surgeons in the operative disciplines field has in recent years further increased. The training of a surgeon and the required lifestyle combined with the work-life balance of the surgeons are perceived as being less attractive, so that young doctors after finishing medical school rarely decide for surgical careers. Changes in the social environment outside of our clinics has resulted in a decline of the social prestige. The modified structural preconditions require a rethinking of the training processes for studying and working conditions in surgery. The quality of surgical education is therefore a cornerstone for the future development of our subject and is directly linked to the training and junior development. The CAQ meeting in Greifswald in February 2009, has focused on the teaching in surgery and developed together with medical students of different faculties solutions for the three major problem factors: teaching, training and junior development. The students are demanding clear guidelines regarding the required theoretical and practical knowledge in the form of catalogues or learning logs. The absence of intrinsic commitment to an excellent teaching and role model is due to the ongoing conflict between patient care and teaching. Because in teaching usually neither the quantity nor the quality will be systematically registered and no sanctions promote the lesson, so that the training is always considered as a last resort. One approach could be a scoring system for teaching that reflect the quantity and quality of teaching in points. The practical year needs to be reformed, since over 25% of the students spend their surgery part abroad, because they are afraid to be considered as cheap labour. Especially at this point, the lecturer is asked to reform the education of students during the practical year and to strengthen the role model for young academic teachers.


Assuntos
Educação de Pós-Graduação em Medicina/normas , Cirurgia Geral/educação , Assistentes Médicos/educação , Garantia da Qualidade dos Cuidados de Saúde/normas , Escolha da Profissão , Currículo/normas , Alemanha , Humanos
4.
J Bone Joint Surg Am ; 85(4): 660-6, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12672842

RESUMO

BACKGROUND: The purpose of this study of distal radial fractures was to compare the radiographic and clinical results after use of a standard four-pin external fixator with those after use of a five-pin fixator with the fifth pin stabilizing the distal radial articular fragment. METHODS: In an open prospective trial, fifty patients with an unstable distal radial fracture were randomized for treatment with closed reduction and either a standard small Association for the Study of Internal Fixation (ASIF) four-pin fixator (twenty-five patients) or a five-pin external fixator (twenty-five patients). The fixators were removed at nine weeks, and all patients were assessed radiographically and clinically at six months. RESULTS: Follow-up radiographs demonstrated significantly less loss of alignment and length with the five-pin external fixator. Pin site infections were more prevalent with the four-pin fixator. The range of motion of the wrist and forearm, the grip strength, and the Lidstrom functional ratings at six months were all significantly better after use of the five-pin fixator. CONCLUSIONS: The use of a five-pin external fixator, with the fifth pin stabilizing the distal radial articular fragment, yields better radiographic and functional results than does a four-pin fixator.


Assuntos
Pinos Ortopédicos , Fixadores Externos , Fixação de Fratura/instrumentação , Fraturas do Rádio/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia , Fraturas do Rádio/diagnóstico por imagem , Resultado do Tratamento
5.
Vasa ; 30(2): 115-21, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11417281

RESUMO

BACKGROUND: Carotid endarterectomy (CEA) is well established as the elective treatment for moderate or severe carotid stenoses with a history of neurologic symptoms. In contrast, the merits of carotid revascularisation performed in emergency in patients with acute stroke or fluctuating neurological deficit remain controversial. PATIENTS AND METHODS: A total of 445 CEAs were performed on 424 patients for 212 (48%) asymptomatic and 233 (52%) symptomatic carotid stenoses within a 5 years period between January, 1995, and December, 1999. Of the latter, CEA was performed in emergency on 16 patients (3.8%) within 4 to 24 hours after the onset of symptoms. Patients selected for urgent surgery fulfilled the following criteria: acute onset of fluctuating hemispheric neurological symptoms, significant carotid pathology, absence of cerebral hemorrhage, uncompromised vigilance and stable cardiopulmonary conditions. Selected patients presented with a crescendo-TIA (n = 7) or fluctuating neurological deficits (n = 9) corresponding to a contralateral carotid stenosis. RESULTS: Following CEA, the neurological deficits improved instantaneously to complete recovery in 9 patients. The symptoms of 4 patients improved to non-disabling deficits, remained unchanged in one and worsened in 2 patients from hemihypaesthesia to hemiparesis. 14/16 patients were discharged within 8 days after admission. The neurologic status after discharge did not deteriorate in any of the patients during follow up of 19.3 +/- 13 months, but improved in 4 of the patients. CONCLUSION: Our retrospective study suggests that rescue CEA may be beneficial for selected patients with stroke in evolution and fluctuating neurological deficits. Careful adherence to selection criteria, intraoperative shunting, intensive care post surgery surveillance and an experienced team are recommended.


Assuntos
Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas , Ataque Isquêmico Transitório/cirurgia , Infarto do Miocárdio/cirurgia , Idoso , Idoso de 80 Anos ou mais , Estenose das Carótidas/diagnóstico , Feminino , Humanos , Ataque Isquêmico Transitório/diagnóstico , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Exame Neurológico , Estudos Retrospectivos , Resultado do Tratamento
6.
J Hand Surg Am ; 25(5): 833-41, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11040298

RESUMO

Hydroxyapatite ceramic made of bovine spongiosa was used as structural support material in a prospective study to correct bone defects experienced after reduction in distal radius fractures. The study took place over a 3-year period (1992-1999) and comprised 14 patients. Osseous integration was analyzed via biopsies and magnetic resonance imaging. Long-term follow-up monitoring involving magnetic resonance imaging in 13 of the 14 patients showed fibrovascular growth within incorporated hydroxyapatite material. Osseous integration was demonstrated in magnetic resonance images by gadolinium uptake and by the presence of osteoid layers and endothelialized vessels. Hydroxyapatite ceramic offers a biologically acceptable alternative to autologous bone when augmenting distal radius fracture fixation.


Assuntos
Substitutos Ósseos , Osseointegração/fisiologia , Fraturas do Rádio/cirurgia , Traumatismos do Punho/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Bovinos , Feminino , Fixação Interna de Fraturas , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/cirurgia , Estudos Prospectivos , Rádio (Anatomia)/patologia , Rádio (Anatomia)/cirurgia , Fraturas do Rádio/patologia , Reoperação , Traumatismos do Punho/patologia
7.
Zentralbl Chir ; 125(1): 2-6, 2000.
Artigo em Alemão | MEDLINE | ID: mdl-10703160

RESUMO

Aneurysms of the subclavian artery are extremely rare and most commonly caused by arteriosclerosis, trauma or thoracic outlet syndrome. Less frequently seen causes also include syphilis, cystic media necrosis or tuberculosis or congenital anomalies. The presence of a subclavian aneurysm can give rise to various symptoms such as a pulsating supraclavicular mass, peripheral embolism or brachial plexus compression. Generally, surgical intervention is undertaken involving ligation and extirpation of the aneurysm followed by interposition of either a saphenous vein- or synthetic vascular graft. Recent diversifications in potential therapeutic strategies include the clinical application of transluminally positioned stents for the treatment of vascular lesions. In the literature review we found more than 260 published cases of surgically treated subclavian aneurysms and additional 17 subclavian aneurysms treated by endoluminal stent application. From 1992-1997 5 subclavian aneurysms were resected in our hospital. In four cases a vein graft of the vena saphena magna and in one case a PTFE graft were used. The sensory ischaemic deficit regressed in the further follow up in four of the five cases. Patency was checked postoperatively by ultrasound sonography, angiography or MR-angiography.


Assuntos
Aneurisma/cirurgia , Artéria Subclávia/cirurgia , Adulto , Idoso , Aneurisma/diagnóstico , Aneurisma/etiologia , Implante de Prótese Vascular , Diagnóstico por Imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Stents
8.
Infect Immun ; 68(3): 1626-32, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10678982

RESUMO

Several products of the activated complement system are known to modulate endothelial cell function in vitro. It has been shown that the membrane attack complex (MAC) (C5b-C9) can enhance tumor necrosis factor alpha (TNF-alpha)-induced expression of P- and E-selectin and intercellular adhesion molecule type 1 in cell cultures of human umbilical vein endothelial cells. In the present study the potential role of this synegism for lung injury during endotoxin-mediated septic shock in vivo was examined using a model of C6-deficient PVG (C-) (RT1(C)) rats and the congenic PVG (C+) (RT1(C)) strain. Following administration of a high (5 mg/kg) or low (0.5 mg/kg) dose of lipopolysaccharide (LPS) (Escherichia coli O55:B5), we determined the expression of cytokines, chemokines, and adhesion molecules as well as the recruitment of leukocytes in the lung. Challenge with intraperitoneal i.p. injections of LPS resulted in a strong induction of TNF-alpha, interleukin-1alpha/beta, cytokine-induced neutrophil chemoattractant, interferon-inducible protein 10, macrophage inflammatory proteins 1alpha and 2, macrophage chemotactic protein 1, and P-selectin. However, there were no significant differences between PVG (C-) and PVG (C+) rats. Immunoperoxidase staining showed a similar increase of lung infiltration by CD11b/c(+) leukocytes in both rat strains. We therefore conclude that the described synergism between TNF-alpha and the MAC of the complement system on the induction of endothelial adhesion molecules is dispensable for inflammatory processes during endotoxin-mediated septic shock in vivo.


Assuntos
Complemento C6/fisiologia , Complexo de Ataque à Membrana do Sistema Complemento/fisiologia , Lipopolissacarídeos/toxicidade , Pneumonia/etiologia , Animais , Quimiocinas/biossíntese , Complemento C6/deficiência , Citocinas/biossíntese , Humanos , Antígeno de Macrófago 1/fisiologia , Masculino , RNA Mensageiro/análise , Coelhos , Ratos , Fator de Necrose Tumoral alfa/fisiologia
11.
Dis Esophagus ; 10(1): 64-8, 1997 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9079278

RESUMO

Postemetic spontaneous rupture of the esophagus is an intrathoracic disaster which is generally lethal if untreated. The tragedy seems to strike more often than commonly suspected. The current literature review focuses on publications since 1980 and includes the retrospective review of 18 additional patients treated in our hospital for spontaneous rupture of the esophagus. Frequently, a wide variety of unspecific symptoms has led to the mistaken diagnosis of an acute abdomen, pancreatitis or cardiac arrest. About 40% of the patients with spontaneous rupture of the esophagus presented a history of alcoholism or heavy drinking and 41% suffered from gastroduodenal ulcer disease. Pain (83%) and vomiting (79%) often associated with dyspnea (39%) and shock (32%) are the major symptoms. This unspecific symptomatology delayed the correct diagnosis of the Boerhaave's syndrome and resulted in a significant complication rate. The mortality rate associated with Boerhaave's syndrome was 50% from the first successful surgical repair in 1947 by Barrett to 1980. After 1980, however, the mortality rate dropped to 31%, because of earlier diagnosis, surgical repair and improvement in intensive care. When surgery is delayed, the prognosis of patients with spontaneous rupture of the esophagus is in general severe.


Assuntos
Doenças do Esôfago/diagnóstico , Abdome Agudo/diagnóstico , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Alcoolismo/complicações , Causas de Morte , Cuidados Críticos , Diagnóstico Diferencial , Dispneia/fisiopatologia , Doenças do Esôfago/fisiopatologia , Doenças do Esôfago/cirurgia , Feminino , Parada Cardíaca/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Dor/fisiopatologia , Pancreatite/diagnóstico , Úlcera Péptica/complicações , Prognóstico , Estudos Retrospectivos , Ruptura Espontânea , Choque/fisiopatologia , Taxa de Sobrevida , Síndrome , Vômito/complicações
12.
Transpl Int ; 10(3): 229-33, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9163865

RESUMO

Methylenedimethoxymethamphetamine (MDMA), more commonly known as ecstasy, is a synthetic amphetamine derivative used by teenagers and young adults in the United States as well as in Western Europe as a "dance drug". Though a number of complications associated with this drug have been reported, there is little information pertaining to hepatoxity as a result of MDMA ingestion. This case report is about an 18-year-old female patient who regularly used ecstasy on weekends over a 2-month period. Within 2 days after accepting a "hit" of the substance at a party, she was admitted to the hospital because of lethargy, vomiting, abdominal pain, stool discoloration, icterus, and darkened urine. On day 7 she developed fulminant hepatic failure with reduced hepatic coagulation factors and grade IV encephalopathy. Orthotopic liver transplantation was carried out 10 days following the ingestion. The patient made a full recovery within 72 h and was released from the hospital 6 weeks later. Histopathological examination of the removed liver revealed a nutritive-toxic liver necrosis. This case demonstrates that the ingestion of ecstasy, even on an infrequent basis, can lead to acute fulminant liver necrosis, and that this life-threatening complication can be treated successfully by liver transplantation.


Assuntos
Falência Hepática Aguda/cirurgia , Transplante de Fígado , N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos , Adolescente , Adulto , Feminino , Humanos , Falência Hepática Aguda/induzido quimicamente , Masculino
13.
Unfallchirurg ; 100(10): 776-81, 1997 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-9446231

RESUMO

Scaphoid fracture is, in most cases, usually still treated conservatively. The disadvantages of long-term immobilization are stiffness of the wrist joint, loss of strength and higher costs. The osteosynthesis of the scaphoid fracture with the Herbert bone screw restores the exact form and length and the normal position of the scaphoid to the other carpal bones. It prevents non-unions, arthrosis and other late complications. The Freehand method is used as a percutaneous technique without utilization of a jig. The scaphoid fracture is treated with closed reduction and osteosynthesis is performed with the Herbert bone screw. The percutaneous technique preserves the inter- and intracarpal ligaments, the vascular supply and the articular surfaces of the scaphoid. Osteosynthesis by the Freehand method is sufficiently stable to withstand early functional moves on the first postoperative day.


Assuntos
Parafusos Ósseos , Ossos do Carpo/lesões , Fixação Interna de Fraturas/instrumentação , Traumatismos do Punho/cirurgia , Adulto , Ossos do Carpo/diagnóstico por imagem , Ossos do Carpo/cirurgia , Feminino , Consolidação da Fratura/fisiologia , Humanos , Masculino , Complicações Pós-Operatórias/diagnóstico por imagem , Radiografia , Instrumentos Cirúrgicos , Traumatismos do Punho/diagnóstico por imagem
14.
J Clin Invest ; 98(2): 503-12, 1996 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-8755663

RESUMO

The complement activation product, C5a, may play a key role in the acute inflammatory response. Polyclonal antibody to rat C5a was used to define the requirements for C5a in neutrophil-dependent inflammatory lung injury after systemic activation of complement by cobra venom factor (CVF) or after intrapulmonary deposition of IgG immune complexes. In the CVF model, intravenous infusion (but not intratracheal instillation) of anti-C5a produced a dose-dependent reduction in lung permeability and in lung content of myeloperoxidase. In C6-deficient rats, CVF infusion caused the same level of lung injury (measured by leak of 125I-albumin) as found in C6-sufficient rats. In the IgG immune complex model of lung injury, anti-C5a administered intratracheally (but not intravenously) reduced in a dose-dependent manner both the increase in lung vascular permeability as well as the buildup of lung myeloperoxidase. Treatment with anti-C5a greatly suppressed upregulation of lung vascular intercellular adhesion molecule-1 (ICAM-1). This was correlated with a substantial drop in levels of TNFalpha in bronchoalveolar fluids. These data demonstrate the requirement for C5a in the two models of injury. In the IgG immune complex model, C5a is required for the full production of TNFalpha and the corresponding upregulation of lung vascular ICAM-1.


Assuntos
Complemento C5a/fisiologia , Imunoglobulina G/farmacologia , Inflamação/fisiopatologia , Pulmão/fisiopatologia , Neutrófilos/fisiologia , Animais , Líquido da Lavagem Broncoalveolar/química , Quimiotaxia de Leucócito , Ativação do Complemento , Complemento C5a/imunologia , Venenos Elapídicos/administração & dosagem , Venenos Elapídicos/toxicidade , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina G/administração & dosagem , Inflamação/imunologia , Infusões Intravenosas , Instilação de Medicamentos , Molécula 1 de Adesão Intercelular/biossíntese , Pulmão/efeitos dos fármacos , Pulmão/patologia , Peroxidase/metabolismo , Coelhos , Ratos , Traqueia , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/biossíntese
15.
Transplantation ; 61(4): 588-94, 1996 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-8610386

RESUMO

A critical role of the complement membrane attack complex (C5b-9) in mediating hyperacute rejection has been demonstrated previously in fully C6-deficient PVG (C-)(RT1c) rats that reject guinea pig cardiac xenografts at a delayed tempo (45 +/- 9 hr; n=16) compared with C6-sufficient PVG (C+)(RT1c) hosts (0.5 +/- 2 hr; n=6). We have investigated whether selective depletion of C6 from Lewis rats by antibody therapy prevents hyperacute rejection. A polyclonal rat-antirat C6 antibody was induced in PVG (C-) recipients by orthotopic liver transplants from congenic PVG (C+) donors. These liver grafts produced high levels of C6 that reconstituted the complement function of PVG (C-) hosts by 7 days, but the recipients responded within 28 days with the synthesis of an IgG1 antibody to rat C6. The antiserum inhibited hemolytic complement activity of Lewis (RT1(1)) rats in vivo and in vitro. The effect of C6 depletion on Xg survival was investigated by injecting Lewis rats with 2 ml of rat-antirat C6 antiserum before and 1 ml after reperfusion of the guinea pig cardiac xenograft. Lewis rats rejected guinea pig cardiac xenografts after treatment with this rat-antirat C6 antiserum in 38 +/ -11 hr (n=3). Treatment with normal control sera from PVG (C-) rats did not prolong guinea pig cardiac xenograft survival in the Lewis rats (1 +/- 0.7 hr; n=3)(P<0.0043). Injection of 3 ml of the IgG fraction purified from the rat-antirat C6 antibody (33 mg/ml) prolonged xenograft survival to 13.6 +/- 4 hr (n=4) compared with the survival of 0.61 +/- 0.3 hr (n=4) after injection of control rat IgG (33 mg/ml) (P<0.005). These results demonstrate that specific depletion of C6 by antibody therapy has a significant effect on guinea pig cardiac xenograft survival in the Lewis rat. These findings further suggest that C6 depletion may be beneficial to patients undergoing hyperacute rejection of xenografts or allografts.


Assuntos
Anticorpos/fisiologia , Complemento C6/deficiência , Transplante de Fígado/imunologia , Animais , Anticorpos/sangue , Anticorpos/farmacologia , Anticorpos Monoclonais/farmacologia , Formação de Anticorpos , Western Blotting , Complemento C6/imunologia , Ensaio de Atividade Hemolítica de Complemento , Sobrevivência de Enxerto/imunologia , Cobaias , Transplante de Coração , Masculino , Ratos , Ratos Endogâmicos Lew , Transplante Heterólogo
16.
Transplantation ; 59(7): 1073-6, 1995 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-7709449

RESUMO

The liver is the major source of complement (C) components, but extrahepatic sources of C, such as macrophages and endothelial cells, have been hypothesized to contribute to inflammation. Our experiments demonstrate that extrahepatically produced C6 can contribute to hyperacute rejection. PVG (RT1c) rats with normal C activity (PVG (C+)) reject guinea pig cardiac xenografts in 0.5 +/- 0.2 hr, but fully C6-deficient PVG (RT1c) rats (PVG (C-)) reject guinea pig cardiac xenografts in 45 +/- 9 hr. PVG (C+) rats, which received liver transplants from PVG (C-) rats and retained all extrahepatic sources of C6, rejected guinea pig cardiac xenografts in 0.6 +/- 0.03 hr (n = 3). PVG (C-) rats, which received bone marrow transplants from PVG (C+) rats, had C6 levels restored to 10% of that of the donor and rejected guinea pig cardiac xenografts in 9 +/- 3.2 hr (n = 5). Thus, extrahepatic sources of C6 can contribute to xenograft rejection.


Assuntos
Complemento C6/biossíntese , Proteínas do Sistema Complemento/farmacologia , Transplante de Coração/imunologia , Transplante Heterólogo/imunologia , Transplante Heterotópico , Animais , Complemento C6/deficiência , Endotélio/citologia , Endotélio/metabolismo , Rejeição de Enxerto/fisiopatologia , Cobaias , Fígado , Macrófagos/metabolismo , Masculino , Ratos , Ratos Endogâmicos
18.
Transplantation ; 59(2): 288-93, 1995 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-7839453

RESUMO

Acute rejection and antibody-mediated hyperacute allograft rejection are affected by activation of the complement cascade. Split products of early complement components influence the localization, activation, and effector functions of platelets, granulocytes, monocytes, and lymphocytes, while the formation of membrane attack complex (C5b-C9) can lead to rapid cell destruction. Therefore, we compared acute and Ab-mediated hyperacute allograft rejection in a recently described model of C6 deficient PVG (C-) (RT1c) rats and their normal counterpart PVG (C+) (RT1c) rats. Cardiac allografts from fully MHC disparate ACI donors were heterotopically grafted into naive and skin graft sensitized PVG (C-) and PVG (C+) rats. ACI cardiac allografts were rejected acutely (8.3 +/- 2 days; n = 7) by naive PVG (C+) recipients, but survived significantly longer in PVG (C-) recipients (22 +/- 10 days; n = 10). Presensitized PVG (C+) rats rejected ACI cardiac allografts hyperacutely in 6.1 +/- 2.4 hr (n = 5). In contrast, ACI cardiac allografts transplanted into presensitized (PVG (C-) rats had markedly longer survival of 91 +/- 14 hr (n = 5). The alloantibody responses of naive PVG (C+) and PVG (C-) recipients 7 days after cardiac allografting, and of presensitized PVG (C+) and PVG (C-) recipients at time of cardiac allografting were not significantly different as measured by flow cytometry against ACI lymphocytes. Immunofluorescence demonstrated deposition of IgM, IgG and C3 in ACI allografts in PVG (C-) as well as in PVG (C+) recipients. Deposition of C6 was only found in grafts rejected by PVG (C+). The significantly longer survival of ACI cardiac allografts in C6-deficient PVG (C-) rats indicates that the membrane attack complex contributes to acute as well as antibody-mediated hyperacute allograft rejection.


Assuntos
Ativação do Complemento/imunologia , Complemento C6/deficiência , Complexo de Ataque à Membrana do Sistema Complemento/imunologia , Rejeição de Enxerto/imunologia , Doença Aguda , Animais , Anticorpos , Sobrevivência de Enxerto/imunologia , Transplante de Coração/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Hipersensibilidade/imunologia , Imunização , Masculino , Ratos , Ratos Endogâmicos ACI , Ratos Endogâmicos , Ratos Sprague-Dawley
19.
J Immunol ; 153(7): 3168-76, 1994 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-8089494

RESUMO

The relative contributions of liver and bone marrow (BM) constituents to systemic C6 production were compared in a rat model. Liver grafts were transplanted from C6-sufficient PVG (RT1c) rats (PVG (C+)) to profoundly C6-deficient PVG rats (PVG (C-)). C6 levels were restored to 32% within 24 h and reached more than 80% of that of the PVG (C+) donor within 7 days post-grafting, which indicates that the liver is a primary source of systemic C6 production. When livers were transplanted from PVG (C-) to PVG (C+) rats (n = 3), levels of C6 dropped to 42% of pretransplant levels within 24 h and remained between 30 and 40% for more than 100 days after grafting. To determine the source of extrahepatic C6 production, BM was transplanted from PVG (C+) to PVG (C-) rats after total body irradiation. Levels of C6 increased from undetectable levels to 5% of C6 levels of the donor PVG (C+) rat within 60 days. Replenishing PVG (C-) recipients with BM after treatment of recipients with busulfan, which preferentially allows reconstitution with donor myelomonocyte stem cells, resulted in restoration of C activity. Treatment with cyclophosphamide before BM transplantation, which preferentially allows reconstitution of lymphoid stem cells, did not restore hemolytic C activity in PVG (C-) rats. These results were confirmed directly by the successful restoration of C activity with BM depleted of lymphocytes by counterflow centrifugal elutriation from PVG (C+) rats. These in vivo experiments demonstrate that the liver is a primary, but not the sole, source of C6 in the rat and that extrahepatic sources, such as myelomonocytes, and not lymphoid cells in the BM produce a significant amount of systemic C6 in the rat.


Assuntos
Complemento C6/biossíntese , Fígado/metabolismo , Animais , Medula Óssea/metabolismo , Células da Medula Óssea , Complemento C3/metabolismo , Feminino , Transplante de Fígado/imunologia , Masculino , Ratos , Ratos Endogâmicos
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