Mycobacterium avium complex activates nuclear factor kappaB via induction of inflammatory cytokines

BACKGROUND: Ultrasonography of the knee is a non-invasive, readily available and low-cost tool for demonstrating peri-articular tissues. OBJECTIVE: To correlate clinical features with US findings in the detection, quantification and follow-up of inflammatory signs of the knee in children with pauci-articular juvenile rheumatoid arthritis (JRA). MATERIALS AND METHODS: US of both knees was performed in 49 patients on the same day as the clinical examination. All joints were classified into two groups by clinical criteria: group A (active disease) or group B (quiescent disease). Thirteen patients underwent one or more follow-up examinations. US was performed with a small-parts, 7.5-MHz, electronic linear probe by using a technique previously reported. Quantitative assessment of any effusion and synovial thickening was evaluated at the level of the suprapatellar bursa. Wilcoxon and Spearman tests were employed to compare US findings between the two groups and to correlate clinical and US findings within each group, respectively. RESULTS: US demonstrated significant increase of effusion and synovial thickening in group A joints. US enabled visualisation of clinically undetected popliteal cysts in three patients. Correlation between clinical and US findings was significant in group A and positive, though not significant, in group B. CONCLUSIONS: US seems to be a sensitive and reliable method for the assessment and monitoring of knee joint involvement in pauci-articular JRA.     

Urokinase expression in transduced endothelial cells

Increased thromboresistance through the release of lytic agents by endothelial cells may improve the patency of endothelial lined prosthetic grafts. We have evaluated the expression of urokinase from cells transduced with a retrovirus containing the gene for a human preprourokinase. Endothelial cells were enzymatically harvested from canine external jugular vein in nine animals and grown to confluence in culture. One-third of these cells served as controls, and the remaining two-thirds were transduced via incubation with an LXSN-type retroviral vector carrying the urokinase gene and a neomycin resistance gene. Successfully transduced cells were selected by incubation with 400 micrograms/mL G418 and pure cultures grown to confluence. Supernatants from confluent control and experimental cell cultures after 48 hours in defined, serum-free medium were assayed for human urokinase concentration and overall enzyme activity. ELISA quantitation of concentration using mouse antihuman urokinase antibody showed 0.15 +/- 0.11 ng/mL/hr/10(6) cells in the transduced cell supernatant; no measurable concentration was found in the control cells. (P < 0.01) Overall (human plus canine) enzyme activity of urokinase was determined using an indirect spectrophotometric assay based on plasminogen activation (ploug U/mL). Transduced cells showed activities of 0.12 at 10 days and 0.45 at confluence; control cell activity was 0.0 and 0.15, respectively. (P < 0.05) These data show that endothelial cells can be transduced with a urokinase expressing gene that increases the release of this thrombolytic agent. Lining small diameter prosthetic grafts with these cells may improve their thromboresistance and long-term patency.     

Human fibroblasts downregulate plasminogen activator inhibitor type-1 in cultured human macrovascular and microvascular endothelial cells

We have previously reported that plasminogen activator inhibitor type-1 (PAI-1) expression in endothelial cells (ECs) can be modulated differently by smooth muscle cells depending on their origin. Human pulmonary artery smooth muscle cells (HPASMCs) strongly downregulated PAI-1 expression in ECs. Fibroblasts (FBs) are another cell type that could come in close contact with ECs. Therefore, it was the aim of this study to investigate whether FBs could also influence the fibrinolytic potential of ECs. As in the case of HPASMCs, PAI-1 antigen produced by human umbilical vein ECs (HUVECs) cocultured with human skin FBs (HSFBs) was significantly lower as compared with the sum of PAI-1 secreted by the respective cell types cultured separately. Not only HUVECs but also human skin microvascular ECs (HSMECs) responded in a dose-dependent way to serum-free conditioned media (CM) from HSFBs from one individual donor. Similar results were obtained when CM from HSFBs from four other individual donors were used. PAI-1 mRNA decreased in HUVECs incubated for 6 hours with HSFB-CM to 24% to 55% of control, depending on the preparation of HSFBs used. A significant PAI-1 downregulatory effect was only observed when CM from low-passage HSFBs (up to passage no. 5) was used, whereas no reduction in EC PAI-1 production was observed with CM obtained from HSFBs in passage no. 8. This PAI-1 downregulatory activity present in HSFB-CM was heat-labile and had a molecular mass of approximately 5 kD. When CM from HPASMCs was analyzed in the same way, an almost identical elution profile was found. In conclusion, our data showed that FBs can decrease the expression of PAI-1 in ECs. Such an effect could be operative during wound-healing and at other capillary sites where FBs could render ECs profibrinolytic, thereby facilitating processes requiring an increase in proteolytic activity such as EC migration and proliferation.     

Neoplasms of the nasal passages and paranasal sinuses in domesticated animals as reported by 13 veterinary colleges

Three hundred cases of primary neoplasms involving the nasal cavity or paranasal sinuses were found among the reports of 12,300 microscopically confirmed neoplasms. The multispecies data were compiled from abstracts of medical records by 13 colleges of veterinary medicine in the United States and Canada from 1964 to 1973. Significant numbers of neoplasms were observed in dogs, horses, and cats. Intranasal neoplasms were more frequent than those of the paranasal sinuses in dogs and cats. Only cats had a sex difference in the occurrence of nasal neoplasms, with a male predilection. The frequency of neoplasms of the nasal cavity and paranasal sinuses increased with age in all species examined. A clear relationship could not be established between nose length and of intranasal neoplasms. Of the tumors, 80% were malignant in dogs, 68% in horses, and 91% in cats. Detailed review of medical records in a subset of 49 dogs with neoplasms of the nasal passage and paranasal sinuses revealed major clinical signs of nasal and ocular discharge, facial deformity, and stertorous breathing. Median duration of signs prior to diagnosis was 3 months and 95% of the dogs had been given treatment prior to definitive diagnosis. All 49 tumors were malignant; 27 were classified histologically as carcinomas and 22 were sarcomas. Nineteen dogs were treated, using surgery alone or in combination with radiation therapy. Median survival duration was 5 months (mean 6.7 mo).     

Surgical treatment of combined valvular disease in 680 patients

Between 1982 and May 1993, we operated on 680 patients with combined valvular disease. Previous operations were including closed mitral commissurotomy in 87, and bioprosthetic valve replacement in mitral position in 15. The types of combined valve disease included mitral valve disease combined with functional tricuspid regurgitation (FTR) (245), with organic tricuspid disease (OTD) (10); mitral and aortic disease (258), combined with FTR (128), and with OTD (39). The early mortality was 4.7% in total 2.4% and 6.1% respectively in MVR or DVR plus tricuspid procedures. The main cause of early death was low cardiac output syndrome. The late mortality was 2.6% pt-yr, congestive heart failure and coagulant-related hemorrhage were the predominant causes of late death. We considered that FTR is the outcome of right ventricle decompensation, while tricuspid valve must be actively inspected intraoperatively, and must be corrected completely. OTD can be successfully repaired in most patients. Myocardial protection should be emphasized, and continuous perfusion of cold blood cardioplegia and controlled reperfusion of warm blood contained mannitol have marked effect.     

Enoxaparin for unstable angina and ancrod for cardiac surgery following heparin allergy

OBJECTIVE: To describe a patient who presented with heparin allergy and required alternate anticoagulation for unstable angina and coronary artery bypass surgery. To review therapeutic alternatives to porcine heparin for patients with hypersensitivity or intolerance to standard heparin anticoagulation. CASE SUMMARY: A 74-year-old man with a 15-year-old coronary artery bypass graft presented to the emergency room with unstable angina and was scheduled for urgent coronary artery revascularization. A bolus dose of porcine heparin was administered followed by a continuous infusion. Shortly afterward the patient developed a type I allergic reaction to the porcine heparin that was confirmed by rechallenge. Three alternatives to porcine heparin were tried, including bovine lung heparin, low-molecular-weight heparin (enoxaparin), and ancrod. The patient was found to be cross-sensitive to bovine lung heparin, but tolerated enoxaparin for unstable angina without cross-sensitivity. Anticoagulation for cardiopulmonary bypass was achieved with an infusion of ancrod that was later reversed with cryoprecipitate. The patient was discharged postoperatively on day 5 without the complication of excessive bleeding. DISCUSSION: Type I allergic reaction to unfractionated heparin is a rare occurrence and could be the result of a variety of factors. Possible causes for the reaction include a porcine protein, a preservative contained in the heparin solution, or a hapten formed between heparin and a plasma protein. We considered four alternatives to heparin anticoagulation: rush desensitization, bovine lung heparin, low-molecular-weight heparin, and ancrod. The patient was cross-sensitive to bovine lung heparin, but was able to tolerate low-molecular-weight heparin (enoxaparin). This was unexpected because enoxaparin is derived from unfractionated porcine heparin. Testing for cross-sensitivity had no value in this case, as two negative subcutaneous test doses were followed by dramatic reactions when the drugs were given intravenously. Although enoxaparin has been used for anticoagulation during bypass surgery, there is more experience with ancrod as an alternative to heparin. Repeat bypass surgery, which normally results in above-average blood loss, was successfully performed with a very low fibrinogen concentration (< 0.15 g/L) during ancrod anticoagulation. CONCLUSIONS: We conclude that ancrod was a safe and effective alternative to heparin for coronary artery bypass surgery in this patient in whom a heparin product had caused a hypersensitivity reaction. We discovered on two occasions that a negative subcutaneous test dose for heparin allergy did not predict a severe type I allergic reaction when the heparin was later administered intravenously. Furthermore, we found that a low-molecular-weight heparin administered subcutaneously for a short period of time did not cause cross-sensitivity in a patient with a type I allergy to unfractionated heparin.     

Rat model for a vascularized laryngeal allograft

A new rat model was developed to reexamine the potential for laryngeal transplantation. The final anatomic derivation evolved from two earlier developmental phases. The first model had only a single arterial anastomosis; the second had an end-to-end arterial anastomosis with an end-to-end arteriovenous shunt. The final product employed an end-to-side arterial shunt and an end-to-side arteriovenous shunt for revascularization. The allografts were sited in tandem with the intact recipient larynges and were not innervated. A total of 16 animals were studied in phase 3; 2 died and the remaining 14 had a 64% arterial patency at intervals of 1 to 14 days. Our purpose is to detail the relevant technical considerations of this new model and compare it with historical controls.