A series of 15 patients with extracranial carotid artery aneurysms: surgical and endovascular treatment.

OBJECTIVES: This is a retrospective review of 15 patients with primary and secondary aneurysms of extracranial carotid arteries treated surgically and endoluminally over 20 years in one centre. PATIENTS AND METHODS: Fifteen aneurysms of extracranial carotid arteries were noticed in the same number of patients: five atherosclerotic, two after previous carotid surgery, six post-traumatic, one inflammatory, one of unknown etiology. All of them were symptomatic. RESULTS: In the group treated surgically some complications occurred in the perioperative time: one haematoma, two transient neurological deficits, one fatal stroke. In the endovascular group of patients no complications occurred after the treatment. One fatal stroke occurred during operation-the patient died on the 43rd postoperative day due to respiratory insufficiency. Two other deaths occurred during the follow-up: one caused by myocardial infarction 10 years after the aneurysm resection, and the second due to a fatal stroke 3 years after aneurysmorraphy. One patient refused treatment and died 9 months after being diagnosed. CONCLUSION: Neurological deficits in patients after neck injuries should arouse the suspicion of the presence of a carotid artery aneurysm. Open repair remains the method of choice in treating carotid artery aneurysms but endovascular procedures create the possibility of treating extracranial aneurysms in selected cases when open surgery is not recommended.

Progress of local symptoms of superficial vein thrombosis vs. duplex findings.

BACKGROUND: Risk of subsequent deep vein thrombosis (DVT) following superficial vein thrombosis (SVT) is not fully appreciated. Mechanisms, time relations and risk factors for DVT arising upon earlier SVT remain unclear. The aim of this study was to analyze time relations between local symptoms of lower limb superficial vein thrombosis, duplex findings and onset of deep vein thrombosis during clinically evident course of SVT. PATIENTS AND METHODS: 46 patients with early (onset less than 72 hours prior to inclusion) clinical diagnosis of SVT, confirmed ultrasonographically were included in this prospective, multicenter study. Progress of pain, erythema and swelling in relation to subsequent ultrasound changes in size and localization of thrombus at 0, 7, 14 and 21 day of study has been recorded. RESULTS: Local symptoms subsided completely during 3 weeks. At that time thrombus disappeared completely only in 26% of cases, in remaining cases decreased in size from average 117.5 mm to 43.0 mm. Thrombus regression was similar to venous blood outflow direction--proximal to femoral area. Thrombus propagation was observed following regression of local symptoms of SVT. 4 cases of DVT (8.7%) were diagnosed at 2-11 days. CONCLUSIONS: Local, clinically detectable symptoms of SVT regress incomparably quicker than thrombus in affected veins. Risk of further thrombus propagation extends well beyond the period of intensive local symptoms of SVT. Regression of thrombus in femoral area requires significantly more time than in popliteal or calf segment. Thrombus propagation is directed with blood flow towards femoral segment.

Fas deficiency exacerbates cerulein-induced pancreatitis.

Acute pancreatitis results in many deaths each year. Our understanding of pathophysiology is limited. To better understand the impact of apoptosis versus necrosis, we compared cerulein-induced pancreatitis in Fas-deficient (MRL lpr/lpr) versus Fas-sufficient (MRL +/+) mice. Average amylase values in Fas-deficient mice were substantially greater than in Fas-sufficient mouse. Histology graded on edema, inflammation, vacuolization, and necrosis showed greater injury in the Fas-deficient mouse. This finding suggests that the Fas pathway is important in controlling cerulein-induced pancreatitis.

Long-term outcomes of renal transplantation: a result of the original endowment of the donor kidney and the inflammatory response to both alloantigens and injury.

Recent data suggest that long-term allograft survival might be affected by two factors. The first is the endowment of the allograft, which consists of two elements: the nephron mass and the ability of these nephrons to repair injuries sustained during the transplant process. The second factor is renal inflammation. Although inflammation is traditionally ascribed to alloreactivity, recent data have shown that there is also a renal inflammatory response to early injury after transplantation, to brain death in the donor, and as part of the maladaptive response to nephron loss. These two factors contribute to the detrimental effects of delayed graft function or acute rejection on the long-term survival seen in most studies, and the beneficial effects of anti-inflammatory agents on the maladaptive response to nephron loss.

Nitric oxide inhibits INFgamma-induced increases in CIITA mRNA abundance and activation of CIITA dependent genes--class II MHC, Ii and H-2M. Class II TransActivator.

BACKGROUND: Nitric oxide (NO) has been recently implicated as a powerful inhibitor of immune responses during allograft rejection, and some autoimmune and infectious diseases. We previously showed that one potential regulatory effect of NO is inhibition of IFNgamma-stimulated expression of Class II MHC on macrophages. Activation of this gene is mediated by the "Class II TransActivator" (CIITA). We now ask whether NO inhibits CIITA and thus the family of genes regulated by CIITA--Class II MHC, Ii, and H-2M. The latter two genes participate in antigen processing and formation of the cell-surface peptide-Class II MHC complex. METHODS: Murine macrophages--both peritoneal macrophages and the RAW264.7 macrophage line--were stimulated in vitro with IFNgamma. NO production was measured by the Greiss reagent. Transcription of Class II MHC was measured by nuclear run-on assay. mRNA abundance of Class II MHC, Ii, H-2M, and CIITA was measured by Northern blotting and RT-PCR. RESULTS: NO inhibits IFNgamma-induced increases in the abundance and transcription of the Class II MHC Ab gene. The increases in mRNA abundance of CIITA, Ii, and H-2M are also inhibited. As a control, we found that NO did not inhibit LPS-induce increases in TNFalpha mRNA abundance. CONCLUSIONS: NO inhibits IFNgamma-induced increases in CIITA, and thus inhibits the CIITA-regulated genes: Class II MHC, Ii, and H-2M. Early during rejection, NO production by macrophages may result after stimulation by IFNgamma produced by CD4+ T cells, and be an effector of allograft damage. High concentrations of NO may then act as a feedback inhibitor which decreases antigen presentation by macrophages and thus decreases CD4 T cell activation.

Docosahexaenoic acid decreases IRF-1 mRNA and thus inhibits activation of both the IRF-E and NFkappa d response elements of the iNOS promoter.

BACKGROUND: Nitric oxide produced by inducible nitric oxide synthase (iNOS) may be cytotoxic during cardiac, hepatic, and renal acute allograft rejection. Because the incidence of rejection is decreased by fish oils that contain docosahexaenoic acid (DHA), we investigated the effects of DHA on iNOS. Using nuclear run-on assays and iNOS-promoter constructs, we previously showed that docosahexaenoic acid (DHA) inhibits activation of the iNOS gene by murine macrophages that had been stimulated in vitro by IFNgamma plus lipopolysaccharide. METHODS: In our current investigation, our purpose has been to determine how DHA inhibits iNOS gene activation in murine macrophages, by using gel retardation and Northern blotting techniques. We studied the effects of DHA on the formation nuclear protein complexes that interact with the critical iNOS promoter's response elements for IRF-1 (IRF-E -923 to -913 bp) and NF-kappaB (NFkappa d -85 to -75 bp). RESULTS: We now show that DHA inhibited increases of IRF-1 mRNA abundance in response to IFNgamma plus lipopolysaccharide. As expected, we found that this prevented formation of the nuclear protein complex that binds to the IRF-E DNA response element. We also found that inhibition of IRF-1 inhibited formation of the nuclear protein complex that binds to the NFkappa d DNA response element. CONCLUSIONS: DHA decreases the abundance of IRF-1 mRNA in stimulated cells. That, in turn, results in the decreased nuclear protein binding to the major iNOS promoter response elements (IRF-E and NF-kappaB). We found that this occurred because IRF-1 is a component of both the nuclear protein complex that binds to IRF-E and the nuclear protein complex that binds to NFkappa d.

Transplant surgery injury recruits recipient MHC class II-positive leukocytes into the kidney.

BACKGROUND: CD4 T cells, which are stimulated by the "indirect pathway" of antigen-presentation, participate in rejection. These T cells are sensitized by recipient major histocompatibility complex (MHC) class II-positive leukocytes that migrate into the transplant. Therefore, an important early step in rejection is the immigration of these recipient MHC class II-positive leukocytes into the renal transplant. The regulation of this early step is not understood. We now test the hypothesis that such leukocytes immigrate into the renal transplant in response to ischemic injury occurring during the transplant procedure. METHODS: We transplanted Brown Norway (BN) kidneys into F1 Lewis/Brown Norway (L/BN) recipients. The F1 recipients are tolerant to the parental BN antigens, and any infiltration of recipient MHC class II-positive leukocytes results from injury occurring during transplantation surgery. In addition, ischemia/reperfusion injury was also induced by temporarily occluding the native renal arteries for 30 minutes. Transplanted kidneys and native kidneys, which suffered ischemia/reperfusion injury, were studied by immunohistochemistry on days 3, 7, 14, and 28 after surgery. Staining by the new monoclonal antibody (mAb) OX62 and antibodies to MHC class II identified dendritic cells. In addition, the following monoclonal antibodies identified: gamma/delta T cells, V65; B cells, OX33; cells that may be macrophages, dendritic cells, or dendritic cell precursors, ED1 (+) and OX62 (-); and recipient class II MHC, OX3. RESULTS: After transplantation, the serum creatinine increased to 4 mg/dl and then decreased, which was consistent with reversible injury during transplantation and the absence of rejection. We found that the injury of transplantation itself resulted in the infiltration of recipient MHC class II-positive leukocytes into the transplanted kidney. This infiltrate peaked at days 7 to 14 after surgery. The inflammation was peritubular and patchy and involved cortex and outer medulla. Double staining for OX62 and OX3 identified some of the infiltrating leukocytes as dendritic cells. Other recipient leukocytes were MHC class II positive, ED1 positive, and OX62 negative. We also found that MHC class II leukocytes, including dendritic cells, infiltrated native kidneys injured by ischemia/reperfusion injury. CONCLUSION: To our knowledge, this is the first demonstration that injury to the kidney during transplantation recruits recipient MHC class II-positive leukocytes into the kidney. Some of these leukocytes are dendritic cells.

Hypothesis: is renal allograft rejection initiated by the response to injury sustained during the transplant process?

Allograft rejection can be caused by numerous factors such as damage to the donor kidney during surgical removal or implantation, injury sustained during the transport process between the donor and recipient, and suboptimal allograft perfusion during the intra- and post-operative period. In cadaveric allografts, damage can occur during cold storage, during the transit stage between donor and recipient, and hemodynamic instability due to the initial damage that caused its removal from the donor (such as brain death or trauma). We hypothesize that rejection requires recognition of this injury in addition to recognition of alloantigens. If indeed injury proves to be one factor in acute rejection episodes, then therapeutic efforts can be made to reduce injury during the transplantation process.

Docosahexaenoic acid, a component of fish oil, inhibits nitric oxide production in vitro.

INTRODUCTION: Docosahexaenoic acid (DHA) has been shown to be immunosuppressive in the fetus, and fish oil diets are thought to be beneficial in autoimmune disease and transplantation. This effect may be mediated through nitric oxide (NO). Here, we investigate the effect of DHA on murine macrophages. METHODS: Peritoneal macrophages were subjected to stimulation with various concentrations of interferon gamma-(IFN-gamma) and tumor necrosis factor alpha (TNF-alpha). NO production was assessed by measuring nitrite (Greiss reaction). RESULTS: At all doses of IFN-gamma and TNF-alpha, DHA was found to be inhibitory to NO production. CONCLUSIONS: DHA inhibits macrophage-stimulated NO production in response to IFN-gamma and TNF-alpha. As NO is thought to be important in several disease processes, DHA may be a useful agent in the treatment of conditions such as autoimmune disease.

Syngeneic renal transplantation increases the number of renal dendritic cells in the rat.

Dendritic cells participate in the regulation of CD4 and CD8 T cells during transplant rejection. Understanding what causes increased numbers of dendritic cells to appear in the renal transplant is therefore important. We performed syngeneic renal transplants between rats. We used the monoclonal antibody OX62 to detect dendritic cells, and OX6 to detect major histocompatability complex (MHC) Class II in the renal transplant. One week after transplant, dendritic cells appeared. This indicates that the injury of transplantation itself is sufficient to increase the number of dendritic cells in the kidney in a model where there is no alloreactivity.

Docosahexaenoic acid, a constituent of fetal and neonatal serum, inhibits nitric oxide production by murine macrophages stimulated by IFN gamma plus LPS, or by IFN gamma plus Listeria monocytogenes.

Murine macrophage activation is deficient in the fetus and the neonate, and in areas of the placenta perfused by the fetal circulation. Fetal and neonatal serum concentrations of docosahexaenoic acid (DHA) are 150 microM, or approximately 50-fold higher than in the adult. We previously showed that DHA inhibits activation of the gene for inducible nitric oxide synthase (iNOS) in murine macrophages stimulated in vitro with interferon gamma (IFN gamma) plus lipopolysaccharide (LPS). We have now pursued these observations in greater depth. An assay system was developed which separated the stimulation of macrophages by IFN gamma plus LPS, and the actual production of nitric oxide (NO). It was found that macrophages do not produce NO until they have been stimulated by IFN gamma plus LPS for a period of 10 h. NO is produced during the subsequent 10 h, even though IFN gamma plus LPS are not longer present. DHA, if present, inhibited only during the initial 10 h stimulation; DHA did not inhibit the production of NO by macrophages which had previously been stimulated by IFN gamma plus LPS, and were already producing NO. It was also found that DHA was less inhibitory if given prior to the IFN gamma plus LPS stimulation. In a dose-responsive manner, DHA inhibited the increased abundance of iNOS mRNA by macrophages stimulated by IFN gamma plus LPS. NO contributes to the host defense against Listeria monocytogenes and other intracellular pathogens. We therefore investigated the ability of DHA to inhibit NO production by macrophages stimulated by IFN gamma plus Listeria monocytogenes in vitro; DHA inhibited transcription of the iNOS gene and also the listeriocidal activity of activated macrophages. Inhibition of NO production by DHA may contribute to the increased susceptibility of the fetoplacental unit and neonate to intracellular infections.

[Variability of pathogenic bacterial flora as a cause of postoperative infection]. / Zmiennosc skladu patogennej flory bakteryjnej bedacej czynnikiem etiologicznym zakazen pooperacyjnych.

The author discussed the results of investigations concerning pathogenic bacterial flora variation causing infection in a surgery ward. Data obtained in the period 1995-1996 were analysed. Covering 118 cases of postoperative infections and 72 cases of primary infections, treated surgically. To establish drug-sensitivity of the bacteria causing infections, the infected samples were taken from all these patients. It was found that different kinds of bacteria caused the postoperative and the primary infections. It was also noted that there was different progress in drug-resistance in each group. The author thing that drug-resistance monitoring in a surgery ward can make antibiotic choice easier in the case of infections, before establishing drug-sensitivity of infection-causing bacteria.

[Iatrogenic reasons for conversion after laparoscopic cholecystectomy]. / Jatrogenne przyczyny konwersji po laparoskopowej cholecystektomii.

The authors discusses causes of conversion after laparoscopic cholecystectomy (LC). 16 cases of technical and emergency conversions have been presented. The link between the experience of the surgeon and the frequency of such conditions has been emphasized. It has been established that emergency conversion is a complication in LC, while technical conversion negatively affect this technique but is likely to reduce the number of major complications.