RESUMO
The BK polyoma virus has, in recent years, become a significant cause of renal allograft dysfunction and failure. Among 260 adult kidney transplant recipients, those with biopsy-proven BK virus nephropathy (BKVN) were compared with those without BKVN with regard to gender, age, race, rejection episodes, time on dialysis, number of organs transplanted, HLA match, live donor versus deceased donor, cold ischemia time, delayed graft function, cytomegalovirus (CMV) serostatus of donor and recipient, induction therapy, and maintenance immunosuppression. Episodes of rejection (35.7% of patients with BKVN vs 8.5% of patients without BKVN; P = .01), transplantation of >1 organ (35.7% of patients with BKVN vs 9.0% of patients without BKVN; P = .01), positive CMV serology in both donor and recipient (71.4% of patients with BKVN vs 41.1% of patients without BKVN; P = .03), and a greater cumulative dose of daclizumab use at the time of induction (2.24 ± 0.05 mg/kg in patients with BKVN vs 2.03 ± 0.14 mg/kg in patients without BKVN; P = .04) were statistically significant risk factors for the development of BKVN. Those who developed BKVN received a higher mean cumulative dose of rabbit antithymoglobulin for induction therapy, but that difference failed to achieve statistical significance (P = .07).
Assuntos
Vírus BK , Nefropatias/virologia , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/etiologia , Infecções Tumorais por Vírus/etiologia , Adulto , Soro Antilinfocitário/uso terapêutico , Biópsia , Feminino , Humanos , Terapia de Imunossupressão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Transplantados , Transplante Homólogo/efeitos adversosRESUMO
Sarcoidosis is an unusual disorder of unknown etiology. Clinically apparent renal involvement is rare in sarcoidosis. The incidence of recurrence in transplant recipients is unknown with few cases having been reported previously. Herein we report a case of sarcoidosis involving a renal allograft that occurred 3 years after transplantation and provide a literature review.
Assuntos
Nefropatias/complicações , Transplante de Rim/efeitos adversos , Insuficiência Renal/cirurgia , Sarcoidose/complicações , Biópsia , Humanos , Imunossupressores/uso terapêutico , Nefropatias/diagnóstico , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Recidiva , Insuficiência Renal/diagnóstico , Insuficiência Renal/etiologia , Sarcoidose/diagnóstico , Fatores de Tempo , Resultado do TratamentoRESUMO
This study compares outcomes of kidney transplantation with two distinct induction protocols Basiliximab (Simulect) versus Muromonab (OTK 3) in the setting of cyclosporine (Neoral)-based immunosuppression. Postinduction protocols included either total prednisone avoidance or prednisone sparing versus standard prednisone dosing. Two hundred forty five adult patients receiving kidney transplantation between 1995 and 2000 were included in the study. Treatment in group 1 was OKT 3 + Neoral + adjunct + standard prednisone; group 2, Simulect + Neoral + adjunct + steroid sparing; group 3, Simulect + Neoral + adjunct + no prednisone. The demographics between all groups were similar. The mean (+/- SD) trough cyclosporine levels at 1 month were 276 +/- 128 versus 291 +/- 180 versus 398 +/- 365 (P=.020); at 3 months were 261 +/- 120 versus 280 +/- 152 versus 399 +/- 408 (P=.32); at 12 month were 235 +/- 144 versus 245 +/- 154 versus 234 +/- 132 (P=.96). Creatinine clearance at 1 month was 59 +/- 24 versus 58 +/- 18 versus 47 +/- 23 mL/min (P=.004); at 3 months was 66 +/- 28 versus 62 +/- 22 versus 53 +/- 25 mL/min (P=.007); at 12 months was 68 +/- 38 versus 65 +/- 22 versus 64 +/- 29 mL/min (P=.556). Serum creatinine at 1 month was 1.8 +/- 0.9 versus 1.6 +/- 1.2 versus 2.8 +/- 2.21 mg/dL (P=.005); at 3 months was 1.7 +/- 0.6 versus 1.9 +/- 1.0 versus 2.3 +/- 1.3 mg/dL (P=.007); at 12 months was 1.9 +/- 1.3 versus 2.1 +/- 1.0 versus 2.3 +/- 1.7 mg/dL (P=.179). The incidence of acute rejection within 1 year in the respective groups were 28% versus 15% versus 16%. Therefore, we conclude that using Simulect in transplant recipients results in long-term patient and graft survival similar to those achieved with OKT 3. The use of Simulect resulted in significant reduction in clinical rejection incidence within the first year regardless of steroid use. Thus, the use of Simulect allows complete steroid avoidance in Neoral-based immunosuppression regimen.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Ciclosporina/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Proteínas Recombinantes de Fusão/uso terapêutico , Anticorpos Monoclonais/administração & dosagem , Basiliximab , Creatinina/metabolismo , Ciclosporina/sangue , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Terapia de Imunossupressão/métodos , Imunossupressores/administração & dosagem , Transplante de Rim/mortalidade , Transplante de Rim/fisiologia , Masculino , Pessoa de Meia-Idade , Muromonab-CD3/uso terapêutico , Proteínas Recombinantes de Fusão/administração & dosagem , Análise de Sobrevida , Fatores de TempoAssuntos
Inibidores de Calcineurina , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/fisiologia , Imunossupressores/uso terapêutico , Transplante de Rim/fisiologia , Muromonab-CD3/uso terapêutico , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Prednisona/uso terapêutico , Negro ou Afro-Americano , Idoso , Demografia , Quimioterapia Combinada , Feminino , Seguimentos , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Transplante de Rim/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Doadores de Tecidos/estatística & dados numéricos , Estados UnidosAssuntos
Anticorpos Monoclonais/uso terapêutico , Ciclosporina/uso terapêutico , Transplante de Rim/fisiologia , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Prednisona/uso terapêutico , Proteínas Recombinantes de Fusão , Adulto , Basiliximab , Creatinina/sangue , Feminino , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto/fisiologia , Humanos , Imunossupressores , Transplante de Rim/imunologia , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
Heart transplant rejection is characterized pathologically by myocyte necrosis and apoptosis associated with interstitial mononuclear cell infiltration. Any one of these components can be targeted for noninvasive detection of transplant rejection. During apoptotic cell death, phosphatidylserine, a phospholipid that is normally confined to the inner leaflet of cell membrane bilayer, gets exteriorized. Technetium-99m-labeled annexin-V, an endogenous protein that has high affinity for binding to phosphatidylserine, has been administered intravenously for noninvasive identification of apoptotic cell death. In the present study of 18 cardiac allograft recipients, 13 patients had negative and five had positive myocardial uptake of annexin. These latter five demonstrated at least moderate transplant rejection and caspase-3 staining, suggesting apoptosis in their biopsy specimens. This study reveals the clinical feasibility and safety of annexin-V imaging for noninvasive detection of transplant rejection by targeting cell membrane phospholipid alterations that are commonly associated with the process of apoptosis.
Assuntos
Anexina A5 , Rejeição de Enxerto/diagnóstico por imagem , Transplante de Coração/diagnóstico por imagem , Transplante de Coração/imunologia , Compostos de Organotecnécio , Cintilografia/métodos , Adulto , Idoso , Apoptose , Transporte Biológico , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Miocárdio/imunologia , Miocárdio/patologiaAssuntos
Insuficiência da Valva Aórtica/etiologia , Insuficiência da Valva Aórtica/fisiopatologia , Coração Auxiliar/efeitos adversos , Disfunção Ventricular Esquerda/fisiopatologia , Ecocardiografia , Transplante de Coração , Humanos , Masculino , Pessoa de Meia-Idade , Falha de Prótese , Disfunção Ventricular Esquerda/cirurgiaAssuntos
Anticorpos Monoclonais/uso terapêutico , Ciclosporina/administração & dosagem , Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Hemissuccinato de Metilprednisolona/uso terapêutico , Muromonab-CD3/uso terapêutico , Ácido Micofenólico/uso terapêutico , Proteínas Recombinantes de Fusão , Basiliximab , Rejeição de Enxerto/prevenção & controle , Humanos , Ácido Micofenólico/análogos & derivados , Indução de RemissãoAssuntos
Hepatite C/mortalidade , Transplante de Rim/mortalidade , Doença Aguda , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Hepatite C/imunologia , Anticorpos Anti-Hepatite C/sangue , Humanos , Transplante de Rim/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
Ulcerative lesions of the penis have many possible etiologies, including infectious, neoplastic, traumatic, drug-induced, and autoimmune. Although the most frequent neoplasm presenting as an ulcerative penile lesion is squamous cell carcinoma, it may rarely be a manifestation of other malignancies, including those of hematolymphoid origin. We report a case of ulcerative balanoposthitis as a manifestation of chronic lymphocytic leukemia. Chronic lymphocytic leukemia and other hematolymphoid malignancies should be considered in the large differential diagnosis of nonhealing penile ulcers.
Assuntos
Balanite (Inflamação)/etiologia , Balanite (Inflamação)/patologia , Leucemia Linfocítica Crônica de Células B/complicações , Úlcera Cutânea/etiologia , Úlcera Cutânea/patologia , Idoso , Evolução Fatal , Humanos , Masculino , Insuficiência de Múltiplos Órgãos , Pênis/patologiaRESUMO
Tissue factor (TF), the initiator of coagulation, has been implicated as a critical mediator of arterial thrombosis. Previous studies have demonstrated that TF is rapidly induced in the normal rodent arterial wall by balloon injury, but is not associated with fibrin deposition. A second injury, however, performed 10-14 days after the first, is followed by small platelet-fibrin microthrombi. This study was undertaken to better localize active TF in balloon-injured rat arteries and to explore possible mechanisms underlying the apparent discrepancy between injury-induced TF expression and the lack of large platelet-fibrin thrombi. By immunohistochemistry, TF antigen was first detected in the media 24 h after injury to rat aortas, and subsequently accumulated in the neointima. Using an ex vivo flow chamber, no TF activity (Factor Xa generation) was found on the luminal surface of normal or injured aortas. Wiping the luminal surface with a cotton swab exposed TF activity in all vessels; levels were increased approximately 3-fold in arteries containing a neointima. The exposed TF activity was rapidly washed into the perfusate, rendering the luminal surface inactive. The loss of luminal TF into the circulation may attenuate thrombosis at sites of arterial injury.
Assuntos
Angioplastia Coronária com Balão/efeitos adversos , Tromboplastina/metabolismo , Túnica Íntima/metabolismo , Animais , Aorta Abdominal/lesões , Aorta Torácica/lesões , Arteriopatias Oclusivas/etiologia , Fibrina/metabolismo , Masculino , Microscopia Eletrônica de Varredura , Ratos , Ratos Sprague-Dawley , Recidiva , Trombose/etiologia , Túnica Íntima/lesõesRESUMO
Recent studies have demonstrated that heparin may protect against reperfusion injury through a direct effect on the microvascular endothelium that is independent of its effect on systemic coagulation. The purpose of this study was to determine whether local delivery of low-dose heparin has a role in the salvage of musculocutaneous flaps after secondary venous ischemia and revascularization. Cutaneous maximus musculocutaneous flaps were transplanted to the contralateral groin in adult Sprague-Dawley rats. All flaps were subjected to 2 hours of primary arteriovenous ischemia followed by 20 hours of reperfusion. The flaps were then subjected to a 6-hour secondary venous ischemic insult followed by anastomotic revision and reperfusion. Animals in group I received no adjunctive treatment. Those in group II were treated with low-dose heparin (5-6 U per kilogram per hour) infused systemically via the inferior epigastric vein. Those in group III received the same dose of heparin infused locally into the flap via the inferior epigastric artery. The dose of heparin used in groups II and III was insufficient to prolong the activated partial thromboplastin time above normal values. At 7 days, mean flap necrosis was 60.8% in group I and 62.1 in group II. Local heparin delivery (group III) resulted in complete survival of all flaps. Histological examination after 48 hours of reperfusion demonstrated improved microvascular patency and reduced neutrophilic infiltration in the flaps of group III animals. Thus, local infusion of low-dose heparin resulted in significantly improved flap salvage through a mechanism independent of its effect on systemic coagulation.
Assuntos
Anticoagulantes/uso terapêutico , Endotélio Vascular/efeitos dos fármacos , Heparina/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Retalhos Cirúrgicos/irrigação sanguínea , Animais , Anticoagulantes/administração & dosagem , Heparina/administração & dosagem , Masculino , Necrose , Tempo de Tromboplastina Parcial , Ratos , Ratos Sprague-Dawley , Retalhos Cirúrgicos/patologiaRESUMO
An occult intrapericardial yolk sac tumor occurred in a 3-year-old girl with a fatal outcome. At autopsy, a 5.5-cm mass surrounded the base of the heart and compressed the left atrium posteriorly. Histologically, the tumor was a pure yolk sac tumor. Postmortem chemical analyses of the blood revealed an alpha-fetoprotein level greater than 7000 microg/L. Acute myocarditis of both ventricles was also found.
Assuntos
Tumor do Seio Endodérmico/patologia , Neoplasias Cardíacas/patologia , Miocardite/complicações , Doença Aguda , Pré-Escolar , Tumor do Seio Endodérmico/complicações , Tumor do Seio Endodérmico/mortalidade , Evolução Fatal , Feminino , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/mortalidade , HumanosRESUMO
We examined 67 explanted Medtronic Freestyle (MF) valves of 0 to 1,490 days of implantation from 66 patients, including 9 full-root, 17 root inclusion, and 41 subcoronary implants derived from a multicenter trial composed of 1,100 patients at 27 centers worldwide (58 valves) and other removed specimens (9 valves). Macroscopic, radiographic and histological examination was performed to establish clinicopathological correlations in retrieved MF stentless aortic bioprostheses. Indications for 30 explants obtained at reoperation were perioperative technical (1 bleeding, 3 iatrogenic valve damage), endocarditis (11), sterile perivalvular leak (4), valve stenosis (1) regurgitation (3), fistula (2), or degeneration (2 cuspal tears, 1 cusp separation). Autopsy specimens were obtained after valve-related (9), non-valve-related (22), or perioperative death (6). Most non-valve-related deaths were cardiac. Valve-related deaths included endocarditis (4), paravalvular leak (1), thrombus (2), subannular occlusion (1), and tamponade (1). No excessive pannus was present. Macroscopic valve thrombosis was noted in two subcoronary implants of 180 and 279 days' duration. Histological analysis on all valves of more than 10 days implant duration or with macroscopic abnormality revealed variable but progressive flattening of the valve cusps; focal, plaquelike unorganized mural thrombus; cuspal fluid insudation; and generalized, nonspecific degenerative changes typical of explanted porcine valves. Aortic wall calcification was seen in two explants of 47 and 49 months' duration, the later with associated cuspal tear. Cusp mineralization was limited to infected valves. No excessive inflammation or fibrosis at the host-device interface was noted. Pathological findings were generally similar to those seen in clinically used glutaraldehyde-fixed xenografts. Potential pathology related to stentless design including pannus, aortic wall calcification, and host-tissue interaction were not clinically significant. Nevertheless, examination of many explanted valves at extended intervals and ongoing clinical data are needed to confirm the long-term efficacy, safety, and characteristic modes of failure of stentless bioprostheses.
Assuntos
Valva Aórtica/patologia , Bioprótese , Próteses Valvulares Cardíacas , Ácidos Oleicos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Aorta Torácica/patologia , Feminino , Doenças das Valvas Cardíacas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/patologia , Desenho de PróteseRESUMO
We report a case of an incidental finding of glycogenic acanthosis of the larynx on autopsy in a 79-year-old man who died of myocardial infarction. The lesion was grossly recognized as a white plaque (leukoplakia) on the subglottic compartment of the left side of the larynx. Histological sections revealed thickened squamous mucosa positive for abundant glycogen on periodic acid-Schiff staining. No epithelial dysplasia was noted. The patient had a history of smoking. This case represents the first report of glycogenic acanthosis involving the larynx. This benign condition should be added to the vast differential diagnosis of leukoplakia in this anatomical location.
Assuntos
Doenças da Laringe/patologia , Leucoplasia/patologia , Idoso , Diagnóstico Diferencial , Glicogênio/análise , Humanos , Mucosa Laríngea/química , Mucosa Laríngea/patologia , MasculinoRESUMO
Mycotic aneurysms of the coronary arteries are rare, with 15 reported cases. These frequently fatal lesions usually occur in a setting of subacute bacterial endocarditis involving native valves. The authors present the first report of mycotic aneurysm of the first diagonal coronary artery following infection of a composite aortic graft.
Assuntos
Aneurisma Infectado/etiologia , Bioprótese/efeitos adversos , Aneurisma Coronário/etiologia , Endocardite Bacteriana Subaguda/complicações , Próteses Valvulares Cardíacas/efeitos adversos , Infecções Relacionadas à Prótese/complicações , Infecções Estafilocócicas/etiologia , Adolescente , Adulto , Idoso , Aneurisma Infectado/patologia , Valva Aórtica , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/cirurgia , Bioprótese/microbiologia , Aneurisma Coronário/patologia , Endocardite Bacteriana Subaguda/patologia , Evolução Fatal , Feminino , Próteses Valvulares Cardíacas/microbiologia , Humanos , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/patologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/isolamento & purificaçãoRESUMO
Tissue factor (TF) is a transmembrane glycoprotein that initiates the coagulation cascade. Because of the potential role of TF in mediating arterial thrombosis, we have examined its expression in human aortic and coronary artery smooth muscle cells (SMC). TF mRNA and protein were induced in SMC by a variety of growth agonists. Exposure to PDGF AA or BB for 30 min provided all of the necessary signals for induction of TF mRNA and protein. This result was consistent with nuclear runoff analyses, demonstrating that PDGF-induced TF transcription occurred within 30 min. A newly developed assay involving binding of digoxigenin-labeled FVIIa (DigVIIa) and digoxigenin-labeled Factor X (DigX) was used to localize cellular TF. By light and confocal microscopy, prominent TF staining was seen in the perinuclear cytoplasm beginning 2 h after agonist treatment and persisting for 10-12 h. Surface TF activity, measured on SMC monolayers under flow conditions, increased transiently, peaking 4-6 h after agonist stimulation and returning to baseline within 16 h. Peak surface TF activity was only approximately 20% of total TF activity measured in cell lysates. Surface TF-blocking experiments demonstrated that the remaining TF was found as encrypted surface TF, and also in an intracellular pool. The relatively short-lived surface expression of TF may be critical for limiting the thrombotic potential of intact SMC exposed to growth factor stimulation. In contrast, the encrypted surface and intracellular pools may provide a rich source of TF under conditions associated with SMC damage, such as during atherosclerotic plaque rupture or balloon arterial injury.
Assuntos
Músculo Liso Vascular/metabolismo , Fator de Crescimento Derivado de Plaquetas/farmacologia , Tromboplastina/metabolismo , Aorta , Compartimento Celular , Células Cultivadas , Fator VIIa/metabolismo , Fator X/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reologia , Tromboplastina/genética , Transcrição Gênica/efeitos dos fármacosRESUMO
TF antigen and activity are found in abundance in human atherosclerotic plaques, particularly in the lipid-rich core. TF is also readily induced in the arterial wall by balloon injury and accumulates in the resulting neointima. In chronic atherosclerosis, the macrophage is likely to be the major source of TF within the plaque. TF accumulates as an early event associated with the migration of monocytes to the vessel wall in response to chemoattractants, such as MCP-1, and their differentiation into macrophages. As SMC become activated in the developing plaque, they provide a second source of TF. Macrophages and SMC accumulate lipid and become foam cells, ultimately degenerating into a necrotic core rich in TF. Spontaneous plaque rupture or acute interventions expose active TF in the core to circulating blood, triggering thrombosis. In acute arterial injury, SMC appear to be the chief source of TF. In normal vessels, the induction of TF in the medial SMC is not sufficient to generate fibrin, presumably because the TF is not readily accessible on the luminal surface. In contrast, endothelial denudation of previously injured arteries may expose intimal TF to circulating blood, resulting in rapid fibrin deposition. In advanced human atherosclerosis, it is likely that even in areas that do not contain "unstable" or "stable" plaques, the vessel wall is not normal and more closely resembles that of a previously injured artery possessing an active intima. Interventions, such as balloon angioplasty, coronary atherectomy, or stent placement may expose intimal TF, leading to fibrin deposition. As the initiator of coagulation, TF is a potential target for inhibiting the thrombotic complications of atherosclerosis. TFPI (reviewed in 52) is currently under clinical investigation as an anticoagulant and its effects on intimal hyperplasia in animal models are being studied. Direct factor Xa inhibitors, such as tick anticoagulant peptide (TAP) and leech anticoagulant peptide (ATS), are also under investigation (53-54). Finally, the recent crystallization of TF (55) and the TF:VIIa (56) should provide important new insights into the design of molecules for directly inhibiting TF.
Assuntos
Arteriosclerose/fisiopatologia , Tromboplastina/fisiologia , Animais , Artérias/lesões , Arteriosclerose/etiologia , Endotélio Vascular/citologia , Humanos , Macrófagos/citologia , Músculo Liso Vascular/citologiaRESUMO
Leukotriene B4 is a potent inflammatory mediator that is derived from the 5-lipoxygenase pathway of arachidonic acid metabolism and that has been implicated in the pathophysiology of polymorphonuclear leukocyte-dependent reperfusion injury in a variety of organ systems. The objectives of these investigations were to determine whether inhibition of leukotriene B4 attenuates postischemic polymorphonuclear leukocyte infiltration and subsequent injury in myocutaneous flaps. Anesthetized female Yorkshire pigs were randomized to receive normal saline (n = 8), the 5-lipoxygenase inhibitor diethylcarbamazine (n = 7), or the leukotriene B4 receptor antagonist SC-41930 (n = 7). All animals underwent 6 hours of rectus abdominis myocutaneous flap ischemia followed by 4 hours of reperfusion. In saline-treated controls, flap ischemia was associated with massive polymorphonuclear leukocyte infiltration at 1 and 4 hours of reperfusion (252 +/- 70 and 619 +/- 137 polymorphonuclear leukocytes per 25 high-power fields, respectively). Skeletal muscle neutrophil content was significantly attenuated by pretreatment with diethylcarbamazine (72 +/- 29 and 229 +/- 63 polymorphonuclear leukocytes per 25 high-power fields; p < 0.05) or SC-41930 (25 +/- 3 and 193 +/- 25 polymorphonuclear leukocytes per 25 high-power fields; p < 0.05). Wet-to-dry weight ratios of full-thickness flap biopsies were lower in the diethylcarbamazine and SC-41930 groups (2.98 +/- 0.15 and 2.90 +/- 0.26, respectively) than in the control group (4.13 +/- 0.23; p < 0.01), and mean muscle infarct size, as determined by nitroblue tetrazolium staining, diminished from 47.6 +/- 11.3 percent in controls to 25.1 +/- 6.5 percent in diethylcarbamazine-treated animals and 7.3 +/- 4.8 percent in SC41930-treated animals (p < 0.05). These data indicate that leukotriene B4 plays a critical role in mediating neutrophil-dependent injury in postischemic skeletal muscle flaps.