The effect of revascularization of atherosclerotic renal artery stenosis on coronary flow reserve and peripheral endothelial function.

BACKGROUND: Patients with atherosclerotic renovascular disease (ARVD) are at increased risk of heart disease because of associated hypertension, coronary artery disease, cardiac failure and chronic kidney disease. Although suggested to be beneficial, the cardiac effects of renal artery revascularization have not been well characterized. Our aim was to analyze the effects of percutaneous dilatation of renal artery stenosis (RAS) in ARVD patients on coronary and peripheral vascular function. METHODS: Nineteen ARVD patients [11 females and 8 males, age at study entry (mean ± SD) 69 ± 10 years] were treated by dilatation of unilateral (n = 9) or bilateral (n = 10) RAS, mainly because of uncontrolled or refractory hypertension. The patients were studied before and after the procedure (103 ± 29 days). They underwent echocardiography and peripheral artery endothelial function testing using flow-mediated dilatation (FMD) of brachial artery at rest and during reactive hyperemia. Myocardial blood flow was measured using quantitative PET perfusion imaging at baseline and during dipyridamole-induced hyperemia. RESULTS: Peripheral endothelial function, tested by FMD, as well as systolic blood pressure and left ventricular mass were improved in patients with bilateral RAS. However, myocardial perfusion and coronary flow reserve (CFR) did not change after the RAS dilatation. CONCLUSION: This is the first study to analyze the stage of myocardial perfusion and CFR in ARVD patients. Although peripheral endothelial function, systolic blood pressure and left ventricular hypertrophy were improved in patients with bilateral RAS by revascularization of RAS, it did not have any effect on coronary perfusion.

Value of electron microscopy in kidney biopsy diagnosis.

Kidney biopsy reports given during 2003 were collected from the authors' pathology database. A total of 111 biopsies were performed. Five tumor samples were not studied with electron microscopy (EM). Of the remaining 106 biopsies, 85 were studied with EM. EM was not performed in 10/24 transplant biopsies, or in 11/82 cases of suspected primary kidney disease. The role of EM was evaluated by grouping the samples in 3 categories: (1) EM was essential for diagnosis, (2) EM contributed to the interpretation and cleared uncertainties, and (3) EM had no influence on the diagnostic process. In transplant biopsies EM influenced the final diagnosis in 86% of cases (category 2). In biopsies performed for primary kidney disease EM was essential for diagnosis in 18.3% clearly contributed in 53.5%, and had no influence on the final diagnosis in 28.2% of cases. The study suggests that the importance of EM has not decreased during the last few years. Because only about 25% of the EM reports did not have any influence on the diagnostic process, it is recommended that kidney biopsy protocols should include EM in all biopsy cases, or at least tissue should be reserved for EM studies of all cases. Because of the influence of EM on the diagnostic process the need for EM in pathology training should be emphasized.

Passive immunization with monoclonal antibodies specific for lipopolysaccharide (LPS) O-side chain protects mice against intravenous Yersinia enterocolitica serotype O:3 infection.

Passive immunization with monoclonal antibodies specific for the lipopolysaccharide (LPS) O-side chain protected mice against intravenously given lethal doses of Yersinia enterocolitica O:3 bacteria. On the other hand, passive immunization with monoclonal antibody specific for the LPS core oligosaccharide did not protect mice. Neither antibody was able to protect mice against orally given lethal doses of bacteria. These results indicate that the O-side chain functions as an important antigenic structure during infection, and that immunity to it probably offer protection also in the in vivo situation.

The value of magnetic resonance imaging in screening myeloma lesions of the lumbar spine.

Screening of the skeleton by plain radiography was compared to magnetic resonance imaging (MRI) of the lumbar spine in 41 patients with multiple myeloma. In the lumbar spine, myeloma lesions were detected in 15 patients with radiography and in 28 patients with MRI. Radiography of the lumbar spine was not positive in any of the 13 cases with negative MRI, but in two of them radiography was positive elsewhere in the skeleton. We suggest that plain radiography is the most suitable method for screening all bone areas in multiple myeloma, but MRI of the lumbar spine is needed to study patients with normal radiographs.

Ten-year follow up study of patients from a Yersinia pseudotuberculosis III outbreak.

A Yersinia pseudotuberculosis serotype III outbreak in 1982 was characterized by a high frequency of post-infectious complications. Ten years later 16 out of the 19 patients originally included in the outbreak were reached for a follow up evaluation. Altogether nine patients suffered from chronic joint symptoms. Four of them were HLA B27-positive. Two of these had ankylosing spondylitis; one with severe erosive polyarthritis and secondary amyloidosis which led to uremia requiring haemodialysis and eventually to death, the other with ankylosis of the lumbar spine and sacroiliitis. None of the patients any longer had detectable anti-Yersinia antibodies. The long-term prognosis of Yersinia-triggered reactive arthritis is discussed.

Adhesion protein YadA of Yersinia species mediates binding of bacteria to fibronectin.

The interaction between fibronectin and Yersinia strains was studied. Wild-type Y. enterocolitica strains expressing the virulence-plasmid-encoded adhesion protein YadA adhered strongly to fibronectin-coated coverslips, while their plasmid-cured variants expressed weaker binding. The cloned yadA gene of Y. enterocolitica or Y. pseudotuberculosis conferred fibronectin-binding ability both to Escherichia coli and to Y. psuedotuberculosis strains lacking the YadA protein. The YadA protein did not mediate binding to isolated fragments of fibronectin or to soluble fibronectin.

AB0 and Lewis blood groups in reactive arthritis.

In this study we evaluated secretor status in patients with reactive arthritis. Previous evidence indicates that non-secretion of AB0 and Lewis blood group antigens to saliva and other secretions is associated with susceptibility to certain bacterial infections and certain diseases with suspected autoimmune etiology. Secretor status can be determined based on the Lewis phenotype. We studied AB0, Lewis and Rhesus blood groups of 54 patients with previous reactive arthritis, 26 of whom had uroarthritis and 28 of whom had arthritis after enteric infection. Furthermore, 25 patients with uncomplicated yersiniosis and 57 healthy controls were studied. We did not find any correlation between secretor status and reactive arthritis or gastroenteritis due to Yersinia. AB0 blood group antigen B appeared to be protective against uroarthritis.

Clinical manifestations of Yersinia pseudotuberculosis infection in children.

The clinical manifestations of infection were analysed during an outbreak of 34 cases of Yersinia pseudotuberculosis serotype Ia infection. The diagnosis was based on the results of enzyme immunoassay and verified by stool culture in five cases. The first four patients were pupils from the same school, and information on any signs and symptoms of infection was obtained by questionnaire from pupils of the school. A blood sample was obtained from 101 children. Strong IgM and IgG antibody responses to Yersinia pseudotuberculosis Ia were found in 13 (25%) of the 52 pupils who reported signs and symptoms of infection and in 9 (18%) of the 49 with no manifestations of infection. The vigorous immune response also resulted in effective opsonization of the causative microorganism. The most common symptoms were fever and abdominal pain. Three children operated on because of suspected appendicitis were found to have mesenteric lymphadenitis. Only one patient developed reactive arthritis. Analysis showed that a remarkable proportion of Yersinia pseudotuberculosis infections may be subclinical, and that individual Yersinia pseudotuberculosis strains may have different capacities to cause postinfection complications.

Serum opsonic capacity against Yersinia enterocolitica O:3 in yersiniosis patients with or without reactive arthritis.

The opsonic capacity of 45 sera from patients with reactive arthritis after Yersinia enterocolitica O:3 infection and of 45 matched sera from yersiniosis patients without post-infection complications was studied at 1-3 months, 5-8 months and 12-20 months after the onset of the infection. Antibody-mediated opsonization of virulence-plasmid-containing Y. enterocolitica O:3 was studied by measuring complement-fixation on opsonized bacteria and opsonophagocytic function of the polymorphonuclear leucocytes (PMN). The PMN response against bacteria pre-opsonized by heat-inactivated sera was measured by using a chemiluminescence (CL) assay. The fixation of complement Clq and C3 on bacteria was determined by flow cytometry using fluorescein-conjugated Clq- and C3c-antisera. All the sera were strongly opsonic at the onset of the infection, and this capacity persisted in most of the patients still at the end of the follow-up. No difference was observed in complement-fixing capacity between the sera of the two groups, but the sera from arthritic patients showed stronger augmentation of PMN CL response at the early phase of the infection (P = 0.005 in the presence of complement, P = 0.04 in the absence of complement). These results suggest that enhanced opsonic capacity may play a role in the development of Yersinia-triggered reactive arthritis by leading to strong activation of the PMN and, consequently, to release of inflammatory mediators.

Polymorphonuclear leukocyte chemiluminescence response in HLA-B27 positive and negative arthritic patients.

The polymorphonuclear leukocyte (PMN) chemiluminescence (CL) response to opsonized zymosan reflecting the C3b/C3bi-receptor-mediated PMN respiratory burst activation was studied in 99 arthritic patients typed for the HLA-B27 antigen. The results indicate that the B27 antigen per se is not associated with disturbances in PMN CL response. However, the erythrocyte sedimentation rate showed a correlation with CL, suggesting that the activity of arthritic disease may affect the PMN CL response.

Role of antibodies in the opsonization of Yersinia spp.

We have determined the opsonic capacity of specific antibodies in patient sera obtained after Yersinia infection. The results indicate that Yersinia antibodies lead to complement activation through the classical pathway, thus overcoming the inhibition of complement-mediated opsonization in the absence of specific antibodies provided by the virulence plasmid in Yersinia enterocolitica and Yersinia pseudotuberculosis. Further, antibodies against plasmid-encoded structures, the Yersinia outer membrane proteins (YOPs), are not necessary in this effect. This is indicated by two facts. (i) Monoclonal antibodies directed against the O polysaccharide of Y. enterocolitica O:3 are capable of opsonizing the plasmid-containing bacteria through C1q binding. (ii) Rabbit antisera show opsonic activity when obtained by immunization both with plasmid-containing Y. enterocolitica expressing the YOPs and a plasmid-cured variant not expressing these proteins.

Factors associated with the development of reactive arthritis.

The role of the causative microorganism in the generation of reactive arthritis is decisive, but host factors are also of major importance. Patients who develop reactive arthritis after Yersinia enteritis show several interesting features in the immunological defence against Yersinia when compared to those who recover uneventfully. When all these peculiarities are taken together, they strongly indicate that in the patients developing reactive arthritis the causative microorganism enters host tissues to persist within the body for prolonged periods of time.

Virulence-plasmid is associated with the inhibition of opsonization in Yersinia enterocolitica and Yersinia pseudotuberculosis.

Plasmid-cured variants of virulent strains of Yersinia enterocolitica and Y. pseudotuberculosis were obtained by selection after growth in calcium-deficient medium. To obtain antigen preparations consisting of whole bacteria the original plasmid-containing strains and the plasmid-cured variants were grown in conditions favouring expression of the temperature-inducible outer membrane proteins of Yersinia (YOP) (37 degrees C, calcium-deficient culture medium). The presence or absence of the YOP on the bacteria was verified by immunoblotting. Opsonophagocytosis of YOP-negative Yersinia preparations (YOP-) was compared to that of YOP-containing ones (YOP+) in human polymorphonuclear leukocyte (PMN) chemiluminescence (CL) assay. The attachment of complement C3b on the surface of the bacteria after opsonization with normal human serum was determined by using a fluorescent anti-C3c-antibody and flow cytometry. YOP+ bacteria resisted opsonization in the absence of specific antibodies, as indicated by diminished C3b-fixation on bacteria and weaker CL response. This implies that virulence-plasmid-coded structures provide Y. enterocolitica and Y. pseudotuberculosis with an ability to avoid complement-mediated opsonization and phagocytosis.

Effects of coronary bypass surgery under high-dose fentanyl anaesthesia on granulocyte chemiluminescence.

Phagocytosis provides one of the body's first-line defences against invading bacteria. The present study evaluated granulocyte microbicidal-related oxidative mechanisms by measurement of chemiluminescence responses in the phagocytosis of zymosan, S. aureus, E. coli and N-formyl-methionyl-leucylphenylalanine (FMLP) in 12 patients undergoing coronary bypass surgery under high-dose fentanyl anaesthesia. With preoperative values as a baseline, a significant depression of in vitro responses to zymosan was seen on days 1, 3-4 after operation and to S. aureus and E. coli on days 3-4 after operation, with recovery by days 6-7. Responses to FMLP were unaffected.

An outbreak of Yersinia pseudotuberculosis infection.

Nineteen patients were involved in an outbreak of infection caused by Yersinia pseudotuberculosis serotype 3. No epidemics attributable to this microorganism have been previously reported; the most extensive known cluster of cases involved four children in one family and their pet dog. The key finding in the outbreak described in the present study was the bacteriologic identification of serotype 3 in stool specimens from patients with clinically typical yersiniosis. Twelve cases were identified by isolation of Y pseudotuberculosis from stool specimens. An ELISA permitted serological diagnosis of the remaining seven cases. The antibody response was unusually slow in some patients. A noteworthy feature of the outbreak was the high incidence of postinfection complications, which developed in 10 of 19 patients. In spite of active screening of the respective families and environments of the patients, no transmitting factor was found, and the precise source of the infection remains unknown.