The Sauve-Kapandji procedure for post-traumatic disorders of the distal radio-ulnar joint.

We present the results of a retrospective series of 41 Sauve-Kapandji procedures carried out for complications of fractures of the distal radius. All the operations were undertaken by one surgeon with a mean follow-up of 32 months. A total of 37 patients was available for clinical review. The indications for surgery were pain on the ulnar side of the wrist and decreased rotation of the forearm. Intraperiosteal and extraperiosteal techniques were used for resection of the ulna, with no difference in outcome. Patients were assessed for pain, rotation of the forearm and complications. A Mayo Modified Wrist Score was used. Pain was improved in 25 of the 37 patients, and unchanged in ten. Rotation of the forearm returned to within 7 degrees of the uninjured side. The results are discussed in relation to the presence of preoperative malunion of the distal radius, age and the functional outcome. Age is not a contraindication for this procedure.

The mucosal phase of Listeria infection.

Listeria monocytogenes is an enteroinvasive bacterial pathogen of man and animals. Listeriae have been shown capable of infecting the host by translocating from the intestinal lumen through Peyer's Patches (PP), however, results of experiments now indicate that these facultative intracellular parasites may also translocate through PP-independent routes. With regards to this, on occasion we observed that listeriae were absent from the PP of mice inoculated intragastrically with L. monocytogenes, but were present in the mesenteric lymph nodes of these same mice. These observations suggested that PP were not necessary for listerial translocation from the intestinal lumen. Two experimental approaches were used to determine whether luminal listeriae could indeed infect the host through PP-independent routes. First, since it is known that: 1) following the intragastric inoculation of L. monocytogenes, listeriae rapidly transit the length of the gastrointestinal tract and reside in the colonic lumen for up to a week, 2) the colon lacks PP, and 3) the descending colon and rectum are drained exclusively by the caudal lymph node (CLN), it was determined whether colonic listeriae could access the CLN. Inoculation of listeriae into the rectum of mice resulted in the infection of the CLN which indicated that PP were not required for listerial translocation. Second, since germfree SCID mice lack PP, it was determined whether listeriae could translocate from the intestinal lumen and infect these immunoincompetent mice. Shortly after the intragastric inoculation of L. monocytogenes into germfree SCID mice, listeriae were found in the mesenteries, livers and spleens. These results also indicate that PP are not required for listerial translocation from the intestinal lumen. One possible route of translocation from the intestinal lumen might occur by listeriae entering enterocytes. Results were obtained showing that listeriae were capable of entering cultured mouse small intestine enterocytes. Internalized listeriae were observed to multiply and spread intracellularly between enterocytes.

Roles for tumor necrosis factor and gamma interferon in resistance to enteric listeriosis.

Listeria monocytogenes normally infects the host by translocating from the intestinal lumen. Experiments were carried out to determine if, when, and where tumor necrosis factor (TNF) and gamma interferon (IFN-gamma) function in antibacterial resistance during enteric listeriosis. Groups of normal mice and severe combined immunodeficient (SCID) mice were injected with neutralizing monoclonal antibodies (MAb) specific for each cytokine and then inoculated intragastrically with L. monocytogenes. The course of infection was monitored by enumerating listeriae in gut-associated lymphoid tissues, livers, and spleens. By the third day of infection, bacterial numbers in infected tissues and organs were greatly exacerbated in all mice treated with anti-TNF MAb, whereas bacterial numbers in the organs of mice treated with anti-IFN-gamma MAb did not differ from those present in the respective organs of control mice. However, by the fifth day of infection, bacterial numbers in the organs of anti-IFN-gamma MAb-treated normal mice and SCID mice were much greater than in the corresponding organs of control mice. Experiments with Listeria-immune mice revealed that TNF and IFN-gamma are involved in the expression of anti-Listeria memory immunity; however, it was also found that the anti-IFN-gamma MAb was relatively ineffective in inhibiting the expression of anti-Listeria immunity, whereas a polyclonal anti-IFN-gamma was quite effective.

Insulinoma: a review of current management.

Insulinomas are a relatively rare tumour which occur predominantly in the pancreas. The majority of the tumours are benign, but have profound effects upon the patient. The diagnosis of insulinoma is often elusive, and the management may involve demanding surgery with a significant morbidity. In this review article, all clinical aspects of insulinomas are examined. Particular emphasis is placed on the myriad modes of presentation, and the methods used to localise the tumour pre-operatively. Medical, as well as surgical treatments are discussed and their role in the management of both malignant and benign tumours. Despite potential difficulties encountered in managing patients with this tumour, a large majority may be either cured or achieve useful palliation.

Regulation of mucosal and systemic antibody responses by T helper cell subsets, macrophages, and derived cytokines following oral immunization with live recombinant Salmonella.

We have assessed regulatory Th cell and cytokine responses in mice after oral immunization with recombinant Salmonella (BRD 847) expressing fragment C of tetanus toxoid, since little information is available to explain how these vectors induce mucosal IgA responses. A single dose of BRD 847 elicited serum IgG2a and mucosal IgA anti-tetanus toxoid Ab responses. To assess Th1-and Th2-type responses, CD4+ T cells from Peyer's patches and spleen were restimulated in vitro, and cytokine-specific ELISPOT, ELISA, and reverse transcriptase-PCR assays were used to assess cytokine patterns. CD4+ T cells produced IFN-gamma and IL-2 as well as IL-10, but not IL-4 or IL-5. Although IL-6 was elevated, further purification of cells from in vitro cultures into CD4+ Mac-1- T cells and Mac-1+ CD4- cells revealed that only the latter cell population had consistently elevated IL-6 gene expression, whereas both sorted populations exhibited increased IFN-gamma and IL-10 gene expression. Thus, orally administered recombinant Salmonella expressing fragment C of tetanus toxoid elicited dominant Ag-specific Th1-type responses together with Th2-type cells producing IL-10 in both mucosal and systemic tissues. Macrophages producing IL-6 were also evident. Our results are consistent with the suggestion that Ag-specific Th1 cells and their derived cytokines, IFN-gamma and IL-2, and Th2-derived IL-10 together with IL-6 produced by macrophages provide important signals for the development of mucosal IgA and serum IgG subclass responses in the absence of preferential expression of Th2 cytokines IL-4 and IL-5.

Identification of canine T-lymphocyte subsets with monoclonal antibodies.

A panel of five murine monoclonal antibodies to canine T-lymphocytes were produced. Antibodies 4.78, 12.125 and 8.358 reacted with approximately 18%, 39% and 60% peripheral blood lymphocytes, respectively. Two color flow cytometric analysis showed that lymphocytes expressing 1.140, 4.78, 8.53 and 12.125 were subsets of lymphocytes expressing 8.358. The lymphocytes expressing 8.358 were negative for surface immunoglobulin. The subsets defined by 1.140, 4.78 or 8.53, 12.125 were mutually exclusive and together account for most cells expressing 8.358 in the peripheral blood, spleen, and lymph node. In the thymus, approximately 47% cells were positive for both 1.140/4.78 and 8.53/12.125. SDS-PAGE analysis of radiolabelled thymus cell lysates demonstrated that antibodies 1.140 and 4.78 immunoprecipitated a 32,35 kd heterodimer under reducing conditions and 12.125 immunoprecipitated a single 56 kd chain under reducing and non-reducing conditions. Antibodies 8.53/12.125 and 1.140/4.78 react with canine lymphocyte populations that occur in proportions similar to lymphocytes expressing CD4 and CD8 like molecules in several primate and non-primate species. The molecules recognized by 12.125 and 1.140/4.78 were similar in size and subunit composition to human CD4 and CD8.

Lipopolysaccharide induces recurrence of arthritis in rat joints previously injured by peptidoglycan-polysaccharide.

Rat ankle joints injected intraarticularly with 5 micrograms of group A streptococcal peptidoglycan-polysaccharide (PG-APS) developed an acute course of arthritis. Recurrence of arthritis was induced in 100% of these joints by intravenous injection of as little as 10 micrograms of Salmonella typhimurium lipopolysaccharide (LPS) 3 wk after intraarticular injection. This reaction was similar in athymic and euthymic rats. Buffalo rats were less susceptible than Lewis or Sprague-Dawley rats. Neisseria gonorrhoeae, Yersinia enterocolitica, and Escherichia coli LPS, and S. typhimurium Re mutant LPS, were also active. Re mutant LPS activity was greatly reduced by mixing with polymyxin B. E. coli lipid A was weakly active. An acute synovitis of much less incidence, severity, and duration was seen in contralateral joints injected initially with saline, and in ankle joints of naive, previously uninjected rats after intravenous LPS injection. The intravenous injection of the muramidase mutanolysin on day 0 or 7 after intraarticular PG-APS injection prevented LPS-induced recurrence of arthritis. These studies suggest that the phlogistic activities of lipid A and peptidoglycan might interact in an inflammatory disease process, and that LPS may play a role in recurrent episodes of rheumatoid arthritis or reactive arthritis.

Monoclonal antibodies. Clinical uses and potential.

An overview of monoclonal antibody technology and some examples of its relevance to veterinary medicine are presented in this article. A technical description of the generation of immune spleen cells and hybridization is included. Feline leukemia, canine parvovirus, and their respective diseases are included as examples of cases in which monoclonal antibodies can be applied in the diagnosis and characterization of these diseases and their etiologic agent.

Comparison of tissue reactions produced by Haemophilus pleuropneumoniae vaccines made with six different adjuvants in swine.

Tissue damage caused by six different adjuvants incorporated in a Haemophilus pleuropneumoniae vaccine was compared in swine. The adjuvants compared were four mineral oil compounds, one peanut oil compound and aluminum hydroxide. Inoculations were given in the neck, quadriceps and semitendinosus muscles. The mineral oil adjuvants were highly irritant and caused extensive areas of granulomatous inflammation that were present at eight weeks after injection. The aluminum hydroxide produced smaller lesions that also persisted for eight weeks. Only the peanut oil adjuvant did not produce significant lesions at the site of injection. At two and four weeks, but not at eight weeks postinoculation, lesions in the quadriceps and semitendinosus muscles were approximately twice as extensive as those in the muscles of the neck.

Calcium requirement and virulence of Yersinia enterocolitica.

At an optimal concentration of magnesium, highly virulent wild strains of Yersinia enterocolitica serotype O:8, with an LD50, for mice, of less than 10(3) cell intravenously, had an in-vitro requirement for calcium at 37 degrees C but not at 26 degrees C. Avirulent wild strains of Y. enterocolitica (LD50 greater than 10(7) cells intravenously) did not have this calcium dependence. When grown on calcium-depleted media at 37 degrees C, eight highly virulent strains yielded 0.5--6% large calcium non-requiring, avirulent colonies; the remaining colonies were slow growing, calcium dependent and highly virulent. Like wild avirulent strains, these calcium non-requiring mutants were quickly destroyed in organs within 48 h, even after large intravenous challenge. In contrast the slow-growing calcium-dependent colonies were highly virulent on intravenous inoculation, growing rapidly in the liver, spleen and lungs to produce multiple abscesses. Homogenates of heavily infected organs produced the original proportion of calcium non-requiring colonies when plated on media without calcium. Results of a fluctuation test suggested that the emergence of calcium non-requiring mutants is the result of induction rather than spontaneous mutation.

Nonspecific resistance to infection expressed within the Peyer's patches of the small intestine.

Intraperitoneal or intraduodenal pretreatment of mice with dead Corynebacterium parvum failed to produce significant nonspecific resistance to Salmonella enteritidis infection in the Peyer's patches of the small intestine. However, mice pretreated with a single oral infection of live Listeria monocytogenes were capable of restricting the growth of S. enteritidis in the Peyer's patches. The ability of L. monocytogenes to induce nonspecific resistance was associated with the ability of this organism to cause an increase in the number of macrophages in the Peyer's patches.

Isolation and functional characteristics of adherent phagocytic cells from mouse Peyer's patches.

Attempts were made to isolate adherent phagocytic cells (macrophages) from mouse Peyer's patch cell suspensions. Cell suspensions prepared by teasing apart the Peyer's patches contained no adherent phagocytic cells. However, if Peyer's patch fragments were treated with collagenase to disrupt the tissue matrix, cells prepared in this way contained a subpopulation of adherent phagocytic cells. These cells comprised only 0.1-0.2% of the total nucleated cell population of the Peyer's patch. Similar cells could also be isolated from the Peyer's patches of germ-free mice, but as judged by their ability to ingest opsonized erythrocytes, these cells were less activated than cells from the Peyer's patches of normal mice. Adherent cells from the Peyer's patches of normal mice could present antigen (ovalbumin) to T cells, and Peyer's patches cell suspensions containing adherent cells could be stimulated in vitro to produce an anti-sheep red blood cell plaque-forming cell response in the absence of 2-mercaptoethanol. These studies show that although the frequency of phagocytic adherent cells is extremely low in Peyer's patches, these cells have functions consistent with that of adherent cells in other lymphoid tissues.

A functional relationship between delayed hypersensitivity and antibacterial immunity.

The injection of living Listeria Monocytogenes into the site of a delayed hypersensitivity reaction in the footpads of mice resulted in inactivation of the organism. No such inactivation occurred when L. monocytogenes was injected into normal footpads. A correlation was observed between the magnitude of the delayed hypersensitivity reaction and the level of antibacterial resistance expressed within the delayed hypersensitivity site.

Host defenses in murine malaria: failure of vaccination with formolized blood parasites to protect athymic mice from Plasmodium berghei.

The thymus dependency of immunity to erythrocytic Plasmodium berghei (NYU-2) infection generated in response to injections of Formalin-killed mixed blood parasites was shown by the demonstration that the vaccine protected immunologically intact nu/+ mice, but not their athymic nu/nu littermates.

Two subsets of rat T lymphocytes defined with monoclonal antibodies.

A new monoclonal mouse antibody that recognizes a subset of rat peripheral T cells has been prepared by immunizing mice with rat thymocyte glycoprotein. This antibody, designated MRC OX 8, labels all peripheral T cells that are unlabeled by the previously described W3/25 monoclonal antibody. No peripheral T cells were found that bound both antibodies, but, in contrast, 90% of thymocytes were doubly labeled. Thoracic duct lymphocytes of congenitally athymic nude rats were not labeled by either antibody, but the spleens of such animals contained both W3/25+ cells and MRC OX 8+ cells. These splenocyte subpopulations did not overlap. Using the fluorescence-activated cell sorter to isolate cells binding MRC OX 8 antibody, the phenotype of T cells mediating various T cell functions was established. Combining the present results with those published previously, it is shown that the cells providing help for antibody responses and those mediating graft-vs.-host reactions are phenotypically W3/25+ MRC OX 8-. On the other hand, parental T cells that suppress antibody formation in F1 hosts were identified as W3/25- MRC OX 8+. The relationship between the rat T cell subsets defined by these antibodies and those in the mouse identified by the Ly series of alloantibodies is discussed and a comparison made between teh rat W3/25+ subset and a recently identified human T cell subset.

Plague virulence antigens from Yersinia enterocolitica.

The virulence of Yersinia enterocolitica, biotype 2, serotype O:8, in mice is related to its ability to produce plague V and W antigens. V and W antigens in Y. enterocolitica are shown to be immunologically identical to the previously described V and W antigens of Yersinia pestis and Yersinia pseudotuberculosis.

Cell-mediated immunity to intestinal infection.

Specified pathogen-free B6D2F1 mice were orally infected with various doses of Listeria monocytogenes. Oral inocula containing more than 2.5 X 10(8) live organisms consistently initiated infection in the Peyer's patches (PP) of the small intestine. At lower doses the infection was sporadic, with many mice showing no apparent infection in the PP. The PP appeared to be the only site of tissue invasion and L. monocytogenes survival in the intestinal tissues, as no organisms were recovered from mucosa dissected free of all visible PP. Within the PP, the bacteria multiplied and the infection then disseminated to the mesenteric lymph node (MLN), liver, and spleen. However, bacteria were almost completely eliminated from all tissues, both systemic and gut-associated by 6 days postinfection. Mice given a primary L. monocytogenes infection by the oral route were highly resistant to subsequent intravenous or oral challenge. Likewise, sublethal intravenous infection rendered mice highly resistant to subsequent oral infection. In addition, lymphocytes from the PP, MLN, and spleens of mice recovering from a primary oral infection were able to adoptively transfer immunity to normal recipients. Finally, after oral infection, mice did not display peripheral delayed hypersensitivity to L. monocytogenes antigens until the organisms had penetrated to the spleen.

Development of delayed hypersensitivity in gnotobiotic mice.

Germ-free mice develop low levels of delayed hypersensitivity following exposure to sensitizing doses of sheep erythrocytes, compared to that seen in conventionally raised mice. Infection of the germ-free animal with either Salmonella gallinarum or Salmonella pullorum was followed by extensive growth of the organisms within the intestine and the gut-associated lymphoid organs. As many as 5,000 viable Salmonellae were recovered from the cecal and ileal Peyer's patches as well as the mesenteric lymph nodes. However, neither strain spread significantly beyond the lymph nodes to the blood stream or to the liver and spleen. The gnotobiotic mice developed significant levels of delayed hypersensitivity to the Salmonella protein antigen and could be more readily sensitized to sheep erythrocytes than the germ-free host, despite the fact that Salmonellae were only able to infect the gut-associated lymphoid tissues.

Biochemical identification of rat ART-1 and Ly-1 alloantigens.

The results of this study indicate that the ART-1 and Ly-1 rat alloantigens are synonymous with each other and also with the leukocyte-common (L-C) antigen which has been previously identified as a major glycoprotein of rat thymocytes and T and B lymphocytes. This conclusion is supported by the following observations: (i) when labeling of rat lymphoid cells was studied with a fluorescence-activated cell sorter, the profiles obtained were similar for labeling with ART-1 and Ly-1 alloantibodies and a monoclonal antibody to L-C antigen: (ii) this labeling was almost completely inhibited by purified L-C antigen: (iii) preincubation with L-C antigen completely inhibited binding of the alloantibodies in a cellular radioimmunoassay; (iv) the cytotoxic effect of the alloantibodies was completely abolished by preincubation with purified L-C antigen; (v) the strain distribution of the ART-1 and Ly-1 alloantigens was identical for 11 rat strains and in linkage analysis the ART-1 and Ly-1 alloantigens were found to cosegregate. Genetic linkage studies have shown that the L-C antigen locus is unlinked to the major histocompatibility antigen (RT1), the immunoglobulin light chain (1k) and to the coat color gene (C) loci.