Subject(s)
Graft Rejection/epidemiology , Heart Transplantation/immunology , Immunosuppression Therapy/methods , Prednisone/adverse effects , Actuarial Analysis , Adolescent , Adult , Aged , Follow-Up Studies , Heart Transplantation/mortality , Humans , Immunosuppression Therapy/adverse effects , Incidence , Male , Middle Aged , Retrospective Studies , Risk Assessment , Survival Rate , Time FactorsABSTRACT
PURPOSE: Standard therapy of mycotic aneurysms in the descending aorta consists of thoracotomy and in situ graft placement or extraanatomic bypass. The alternative use of endovascular stent-grafts was evaluated for management of infected aneurysms of the thoracic aorta. MATERIALS AND METHODS: In a retrospective analysis during a 5-year period, 112 patients underwent stent-graft placement for thoracic aortic aneurysms. Three patients (mean age, 68.6; range, 64-70 years) had mycotic thoracic aneurysms. Stent-grafts were constructed from Z stents covered with polyester fabric and were delivered remotely through a catheter under fluoroscopic guidance. RESULTS: Complete thrombosis of the mycotic aneurysms was achieved in all patients. One patient required a second separate stent-graft placement procedure because of migration of the initial device; the second patient underwent surgical repair of a ruptured mycotic abdominal aortic aneurysm followed immediately by stent-graft placement for a chronic mycotic thoracic aneurysm; a third patient underwent repair of two infected false aneurysms secondary to complete rupture of a surgical interposition graft. There were no complications of persistent bacteremia despite placement of the stent-graft device at the site of primary infection, reinfection, delayed rupture, paraplegia, distal emboli, or surgical conversion. One patient died of cardiac arrest at 25 months; there were no perioperative deaths (< or = 30 days). The remaining two patients were alive and well at median follow-up of 24 months (range, 4-25 months). CONCLUSION: Endovascular stent-grafts combined with antibiotic therapy may be an alternative to conventional thoracotomy in managing mycotic aneurysms of the descending thoracic aorta.
Subject(s)
Aneurysm, Infected/surgery , Aortic Diseases/surgery , Blood Vessel Prosthesis Implantation , Stents , Aged , Aneurysm, Infected/diagnostic imaging , Aneurysm, Infected/drug therapy , Anti-Bacterial Agents , Antibiotic Prophylaxis , Aorta, Thoracic , Aortic Diseases/diagnostic imaging , Aortic Diseases/drug therapy , Aortography , Chronic Disease , Drug Therapy, Combination/therapeutic use , Fatal Outcome , Female , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Complications/surgery , Reoperation , Retrospective Studies , Stents/adverse effects , Tomography, X-Ray ComputedABSTRACT
OBJECTIVE: To evaluate F-18 fluorodeoxyglucose positron emission tomography (PET) in terms of its sensitivity and specificity in diagnosing malignant pulmonary nodules and staging bronchogenic carcinoma. METHODS: A retrospective review of any patient that presented to the VA Palo Alto Health Care System with a pulmonary nodule between 9/94 and 3/96 revealed 49 patients (four female, 45 male) age 37-85 (mean 63) with 54 pulmonary nodules who had: chest CT scan, PET scan; and tissue characterization of the nodule. Characterization of each nodule was achieved by histopathologic (N = 44) or cytopathologic (N = 10) analysis. Of the 49 patients, 18 had bronchogenic carcinoma which was adequately staged. Mediastinal PET and CT findings in these 18 patients were compared with the surgical pathology results. N2 disease was defined as mediastinal lymph node involvement by the American Thoracic Society's classification system. Mediastinal lymph nodes were interpreted as positive by CT if they were larger that 1.0 cm in the short-axis diameter. RESULTS: Sensitivity and specificity for the diagnosis of malignant pulmonary nodules using PET was 93 and 70%, respectively. All nodules (N = 3) that were falsely positive by PET scan were infectious in origin. All nodules (N = 4) that were falsely negative by PET were technically limited studies (outdated scanner, no attenuation correction, hyperglycemia) except for one case of metastatic adenocarcinoma. The sensitivity and specificity of PET in diagnosing N2 disease was 67 and 100%, compared with 56% and 100% for CT scan (not statistically significant). However, one more patient with N2 disease was correctly diagnosed by PET than by CT scan. CONCLUSION: PET is a valuable tool in the diagnosis and management of pulmonary nodules and may more accurately stage patients with bronchogenic carcinoma than CT scanning alone.
Subject(s)
Carcinoma, Bronchogenic/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Tomography, Emission-Computed , Adult , Aged , Aged, 80 and over , Carcinoma, Bronchogenic/pathology , Deoxyglucose/analogs & derivatives , Female , Fluorine Radioisotopes , Fluorodeoxyglucose F18 , Humans , Lung Neoplasms/pathology , Lymphatic Metastasis , Male , Mediastinum/pathology , Middle Aged , Neoplasm Staging , Retrospective Studies , Sensitivity and Specificity , Tomography, X-Ray ComputedABSTRACT
This study examined whether posttransplant anti-T cell monoclonal or polyclonal antibody therapy could provide a window of treatment to allow posttransplant total lymphoid irradiation (TLI) to induce tolerance. These experiments were conducted in a high responder strain combination of an ACI cardiac allograft into a Lewis rat. In this situation, treatment with antibody or posttransplant TLI alone is insufficient to induce tolerance, while similar treatments alone have been shown to induce tolerance in low responder strains. The affects of three anti-T cell therapies were compared: anti-CD4 mAb therapy, anti-CD3 mAb, and rabbit antithymocyte globulin (RATG). None of these antibody therapies alone prolonged graft survival indefinitely. Combining anti-CD4 therapy with posttransplant TLI markedly delayed rejection but failed to induce long-term graft survival. Tolerance could be induced by a combination of anti-pan T cell antibody (anti-CD3) and TLI, and, all grafts survived beyond 100 days. RATG failed to prevent graft rejection when used alone or in combination with TLI. However, posttransplant therapy with a combination of RATG, TLI, and single-donor blood transfusion resulted in graft survival beyond 100 days. Recipients bearing long-term donor grafts rejected third-party (PVG) grafts within 2 weeks. Low density donor bone marrow cells used instead of a blood transfusion did not facilitate tolerance. The results indicate that monoclonal or polyclonal anti-pan T cell antibodies, TLI, and a donor blood cell infusion function synergistically in facilitating tolerance to allografts in the posttransplant period.
Subject(s)
Heart Transplantation/immunology , Immunosuppression Therapy/methods , Animals , Antibodies, Monoclonal/therapeutic use , Antilymphocyte Serum/therapeutic use , Blood Transfusion , CD3 Complex , Evaluation Studies as Topic , Graft Rejection/etiology , Graft Rejection/prevention & control , Heart Transplantation/adverse effects , Immune Tolerance , Lymphoid Tissue/immunology , Lymphoid Tissue/radiation effects , Male , Rats , Rats, Inbred ACI , Rats, Inbred Lew , T-Lymphocytes/immunology , Tissue Donors , Transplantation, HomologousABSTRACT
Cyclosporin A-associated nephrotoxicity has precipitated the need to develop new immunosuppressive protocols or agents that have a higher therapeutic index than cyclosporin A. A new immunosuppressive agent, cyclosporin G or norvaline (Nva-2) cyclosporine, has been shown to be potent. The rat heterotopic transplant model (ACI to Lewis) and Lewis rats that had no operation were used to compare cyclosporin G with cyclosporin A (5 mg/kg/day per gavage) with and without azathioprine (5 to 10 mg/kg/day, intraperitoneally) in terms of immunosuppressive efficacy (graft survival), toxicity (mortality, renal histopathology, and serum creatinine and blood urea nitrogen values), and pharmacokinetics (trough whole blood cyclosporine levels as measured by radioimmunoassay on days 14 and 28 of treatment). In this model no statistically significant difference in immunosuppression was shown between the two cyclosporins both with and without azathioprine. Cyclosporin G, however, was associated with significantly less mortality when combination therapy with azathioprine was used. Both cyclosporins were associated with normal serum creatinine values and little histopathologic evidence of nephrotoxicity, except juxtaglomerular apparatus hyperplasia. Comparable cyclosporine levels were achieved when cyclosporin A or G was used as the sole immunosuppressive agent, but significantly higher cyclosporine levels were shown with cyclosporin A than with cyclosporin G when combination therapy with azathioprine was used. Further studies in humans are needed to evaluate whether cyclosporin G will be a clinically useful immunosuppressive agent either alone or combined with other immunosuppressive modalities.
Subject(s)
Azathioprine/pharmacology , Cyclosporine , Cyclosporins/pharmacology , Immunosuppressive Agents/pharmacology , Animals , Azathioprine/toxicity , Cyclosporins/pharmacokinetics , Cyclosporins/toxicity , Drug Therapy, Combination , Heart Transplantation , Hyperplasia , Immunosuppressive Agents/pharmacokinetics , Immunosuppressive Agents/toxicity , Juxtaglomerular Apparatus/drug effects , Juxtaglomerular Apparatus/pathology , Male , Rats , Rats, Inbred LewABSTRACT
Nephrotoxicity has limited the effectiveness of cyclosporine in transplantation therapy and has precipitated the need to develop a new immunosuppressive agent that lacks this nephrotoxicity or has a higher therapeutic index. Prior studies have suggested that cyclosporin G may be equally effective immunosuppressively, but less nephrotoxic than cyclosporine. To compare the immunosuppressive effects of the two agents, graft survival was analyzed in Lewis-Brown Norway rats, which received heterotopic ACl heart allografts and were treated orally with cyclosporin G or cyclosporine at 5 and 10 mg/kg/day. To compare nephrotoxicity the group of rats that had transplantations and an additional group of surgically intact Lewis-Brown Norway rats, treated orally with cyclosporin G or cyclosporine at dosages ranging from 10 to 50 mg/kg/day and for durations ranging from 50 to 180 days, were analyzed in terms of kidney morphology (fibrosis, glomerular damage, interstitial infiltrate, and tubular dilation) and kidney function (blood urea nitrogen and serum creatinine levels) in this model cyclosporin G was significantly less effective than cyclosporine in prolonging graft survival at 5 mg/kg/day but equally effective at 10 mg/kg/day. In addition, cyclosporin G was substantially less nephrotoxic both morphologically and functionally at low (10 mg/kg/day) and high (50 mg/kg/day) dosages. Further studies are indicated to determine the therapeutic index of cyclosporin G and to evaluate its use in combination with other immunosuppressive agents.
Subject(s)
Cyclosporine , Cyclosporins/toxicity , Heart Transplantation , Immunosuppressive Agents/toxicity , Kidney/drug effects , Animals , Cyclosporins/administration & dosage , Graft Survival/drug effects , Kidney/pathology , Male , Rats , Rats, Inbred Strains , Transplantation, HomologousABSTRACT
For no organ is the need more acute than for the lung or heart-lung block. The new improved "freezing" technique with simultaneous use of intravenous prostaglandin E1 will result in reliable and adequate heart-lung block preservation. The lungs are flushed with high-volume (60 ml/kg), low-pressure (less than 20 mmHg), low-flow (15 ml/kg/min), using modified Euro-Collins solution (added 12 Meq/L of MgSO4 and 65 ml/L of 50% Dextrose). Additional topical cooling has been achieved by cold Physiosol and the excised graft is then placed in a plastic bag filled with Physiosol. This static hypothermia has been successfully used with extended ischemia times of more than six hours in primates and almost four hours in man. Forty heart-lung transplantations have been done from March 1981 to September 1986 and nine of them have been performed using this "freezing" technique with prostaglandin E1. Distant graft procurement has been used twice for heart-lung transplantation. All nine most recent patients who have received the graft harvested with this new "freezing" technique are doing well.
Subject(s)
Alprostadil/administration & dosage , Heart Transplantation , Lung Transplantation , Organ Preservation/methods , Cold Temperature , Electrolytes , Heart Arrest, Induced/methods , Humans , Solutions , Tissue Survival/drug effects , Transplantation, Homologous/methodsABSTRACT
Combined heart and lung transplantation was performed in 12 cynomolgus or rhesus monkeys. The donor heart was preserved with 10 ml/kg of cold crystalloid potassium cardioplegia. The lungs were preserved by perfusing the pulmonary artery over 4 minutes with 60 ml/kg donor weight of cold Euro-Collins solution modified with 8 mEq/L of MgSO4. For six animals in group A, the heart and lungs were immediately transplanted with a mean ischemic time of 1 hour 54 minutes. For six animals in group B, the heart and lungs were stored in a cold extracellular electrolyte solution at 2 degrees to 3 degrees C and transplantation was delayed, with a mean ischemic time of 6 hours and 15 minutes. Anesthesia and mechanical volume ventilation were continued for 8 hours postoperatively with the Fio2 regulated to 40% and with 2 cm positive end-expiratory pressure. Arterial Po2 was sampled at 1, 2, 3, 4, 6, and 8 hours after removal of the aortic cross clamp. Animal survival and cause of death were recorded. All animals were successfully extubated by 10 hours after transplantation. The mean arterial Po2 for group B was initially depressed (89 mm Hg 1 hour after removal of the aortic cross clamp) but rapidly recovered. The mean Po2 for both groups A and B was 184 mm Hg 8 hours after reperfusion. There was no significant difference in the mean hourly Po2 between groups A and B except for the first hour after reperfusion. One animal in each group died of pulmonary insufficiency in the early postoperative period.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Heart Transplantation , Lung Transplantation , Organ Preservation/methods , Potassium Compounds , Animals , Cold Temperature , Electrolytes , Graft Rejection , Hypertonic Solutions , Lung/pathology , Macaca fascicularis , Macaca mulatta , Myocardium/pathology , Oxygen/blood , Potassium , Respiratory Function Tests , Time FactorsABSTRACT
Interferon treatment (3.0 x 10(6) units of human leucocyte interferon) was initiated in a 64-year-old woman with acute hepatitis B infection showing a prolonged course. A decline in serum bilirubin, HBsAg and DNA polymerase activity started during the 10-day period of interferon treatment, and 4 weeks after start of treatment the liver function tests were quite normal. It is possible that the interferon treatment had a beneficial influence on the clinical course of the illness and may be worth trying also in acute fulminant cases of viral hepatitis.