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A role for alphabeta T cells in the resistant phase of the Brown Norway rat model of vasculitis.

Administration of mercuric chloride (HgCl(2)) to Brown Norway rats causes Th2 dominated autoimmunity including a caecal vasculitis. Disease peaks 14 days after starting HgCl(2) after which animals immunoregulate spontaneously. In a third phase, if animals are rechallenged with HgCl(2) 6 weeks later they appear resistant, developing only attenuated disease. Previous studies suggested a role for CD8(+) cells as partial mediators of resistance but no groups had studied the role of alphabeta T cells, gammadelta T cells or natural killer (NK) cells in resistance. We used adoptive transfer and in vitro cell depletion to show that alphabeta T cells are also partially responsible for resistance. Donor animals were treated with HgCl(2) or saline and killed 21 days later. Cells from donor spleens were transferred into recipient animals which were challenged with HgCl(2) and killed 14 days later. Test recipients received spleen cells from HgCl(2)-treated donors after in vitro depletion of one subset of cells. Recipients receiving spleen cells from saline-treated donors remained susceptible to HgCl(2)-induced vasculitis; those receiving spleen cells from HgCl(2)-treated donors were resistant. Animals receiving alphabeta T-cell-depleted spleen cells from HgCl(2)-treated donors showed partial reversal of resistance. Our results suggest a role for alphabeta T cells in the resistant phase of the Brown Norway rat model of vasculitis.

Adoptive Transfer↗

Causes of colic and types requiring surgical intervention.

The migration of strongyle larvae is the most common or basic underlying cause of colic in the horse. Disease conditions producing symptoms of colic occur in all sections of the intestinal tract and consist of impactions, torsions, herniations and foreign bodies. Colic also occurs as a result of pre- and post-partum diseases such as torsion of the uterus, haemorrhage, rupture and inversion of the uterus. In general, lesions resulting in circulatory obstruction are the types requiring surgical intervention. There are six general types of small intestine obstruction that lend themselves to surgical treatment; namely, volvulus, herniations, intussusceptions, stenosis of the lumen of the bowel by external bands or by foreign bodies and chronic inflammatory lesions. The large intestine is not subject to the variety of obstructive lesions found in the small intestine. Impactions count for a large percentage of the obstructions seen. A standing laparotomy for diagnostic purposes may be indicated. Small colon impactions are readily treated by standing laparotomy. Enteroliths are of very common occurrence in some areas of the country; they often result in rupture of the colon. Torsions of the colon produce septic shock very rapidly. The left dorsal colon moving medially or laterally and ventrally initiates the torsion. Clockwise rotation is most common. Massive intravenous therapy is needed to maintain hydration. Ventral midline laparotomy gives best access. Surgery must be performed very early to avoid massive tissue necrosis. Survival rate is 30 percent or less. The small colon is also capable of rotation and volvulus, and of strangulation in the umbilical or inguinal ring.

Animals↗

Mucocele of the appendix: an unusual cause of lower abdominal pain in a patient with ulcerative colitis. A case report and review of literature.

The authors report the case of a 60-year-old male patient. In November 2001 he developed intestinal symptoms of bloody diarrhea and abdominal pain. Colononoscopy and biopsy established the diagnosis of ulcerative colitis (proctosigmoiditis). The disease activity was moderate at the beginning. No significant laboratory alterations were found (including CEA, CA19-9), and mesalazine was started orally. He was in remission until November 2003, when he was admitted to our Outpatient Clinic for upper and right lower abdominal pain and bloody diarrhea. Colonoscopy found proctosigmoiditis with a moderate activity, gastroscopy revealed chronic gastritis, laboratory data was normal. Treatment was amended with mesalazine clysma and methylprednisolone (16 mg) orally. Symptoms ameliorated; however, right lower abdominal pain persisted. US and CT examination demonstrated a pericecal cystic mass (11 cm x 3.5 cm). At first pericecal abscess was suspected, as the previous US examination (6 mo earlier) had revealed normal findings. Fine needle aspiration was performed. Cytology confirmed the diagnosis of mucocele. The patient underwent partial cecum resection and extirpation of the mucocele. He recovered well and the final histology revealed a cystadenoma of the appendix. Follow up was started. The patient is now free of symptoms. Although primary adenocarcinoma of the appendix is uncommon, the authors emphasize that preoperative diagnosis of an underlying malignancy in a mucocele is important for patient management; however, it is difficult on imaging studies.

Abdominal Pain↗

Anti-CD8 treatment reduces the severity of inflammatory arthritis, but not vasculitis, in mercuric chloride-induced autoimmunity.

Mercuric chloride (HgCl2) induces a T cell-dependent autoimmune syndrome in Brown-Norway (BN) rats characterized by a humoral response, tissue injury with an accumulation of CD8+ and CD4+ T cells, and an increase in tissue IL-4 mRNA and serum IgE suggesting Th2 cell activation. In other models of autoimmune disease, CD8+ cells act in both anti- and pro-inflammatory capacities, suggesting that functionally distinct CD8+ populations exist in vivo. The effect of treatment with OX8, a depleting anti-CD8 MoAb, on the initiation of HgCl2-induced autoimmunity was assessed in two experiments in a total of 20 BN rats, and compared with 20 animals treated with a control MoAb or PBS. OX8 significantly depleted peripheral blood CD8+ lymphocytes, had no effect on HgCl2-induced anti-collagen or myeloperoxidase antibodies, nor on the incidence or severity of caecal vasculitis. The severity of HgCl2-induced arthritis was significantly reduced in OX8-treated animals; median peak score reduced from 7.5 to 3.0 (experiment 1) and from 7.0 to 4 (experiment 2) (P = 0.009, Mann-Whitney U-test). OX8 treatment also exacerbated the early rise in HgCl2-induced IgE and induced a significant rise in plasma interferon-gamma (IFN-gamma), suggesting that CD8+ cells may have a regulatory influence on Th cell populations. These data provide direct evidence that CD8+ cells may act in a proinflammatory capacity in both this model of autoimmunity and the pathogenesis of inflammatory arthritis.

Animals↗

[Debatable questions of surgical tactics in appendiceal infiltrates and periappendiceal abscess].

The disease course in 68 patients with appendicular infiltrate (AI) and periappendicular abscess (PAA) is analysed. There were 42 men and 26 women at the age of 15-76 years. AI was detected in 12 patients, PAA-in 56 patients. In 39 patients diagnosis was made on the basis of clinical examination, laboratory tests and X-ray examination. Ultrasound examination was used in 19 cases. Conservative treatment appeared to be effective in 7 patients. The abscess developed in 4 patients. In 5 patients the diagnosis of AI was confirmed at the surgery. Opening and draining of the abscess was performed in 35 patients. The transabdominal opening of the abscess in combination with appendectomy was used in 19 patients. The median laparotomy, appendectomy and abdominal drainage were conducted in 2 patients with the break of the abscess into the abdominal cavity that led to the development of disseminated purulent peritonitis. The long-term results after the resolution of the infiltrate and opening of the abscess were analysed in 38 patients. The postoperative complications have developed in 29 patients, reoperation was performed in 7 of them. 2 of the 68 patients died after surgery. The total mortality rate was 2.9%, postoperative mortality-3.4%. Acute liver insufficiency (1) and intoxication (1) were the causes of death.

Abscess↗

Immunopathologic characterization of typhlitis and colitis in juvenile HLA-B27 transgenic rats.

Adult HLA-B27 transgenic rats carrying high copy numbers of human HLA-B27 and beta 2-microglobulin genes spontaneously develop spondyloarthropathy and enterocolitis comparable to human HLA-B27-associated disease. In this investigation, juvenile HLA-27 transgenic rats were utilized to study incipient immunopathologic events in HLA-B27-associated gastrointestinal inflammation. Flow cytometric analysis of peripheral lymphocytes demonstrated distinctive differences in HLA-B27 protein expression and prompted the division of these transgenic rodents into 2 groups: HLA-B27hi and HLA-B27lo. The HLA-B27hi group, which represented 60% of the rats (aged 8-12 weeks) had inflammation in the colon, anorectal junction and cecum but spared the small intestine. Inflammation coexisted with high levels of surface HLA-B27 expression by hematopoietically derived cells as determined by immunofluorescence staining and flow cytometric analysis of intestinal lymphocytes. Inflammation, which was most intense in the cecum and anorectal junction, was characterized by mixed cellular infiltrate, crypt hyperplasia, transepithelial migration of neutrophils and a reduction in goblet cells. T lymphocytes, particularly CD4+ T cells, predominated over other lymphocytes in the inflammatory infiltrate of the lamina propria. Conversely, no inflammation was evident at any level of the gastrointestinal tract in the HLA-B27lo group (8 weeks of age) which constituted 40% of the juvenile transgenic rats. These animals all expressed low level of HLA-B27 protein. Collectively, these data indicate that HLA-B27 protein expression increases dramatically from 8 to 12 weeks of age and that the level of protein expression and intestinal inflammation are interrelated. These associated gastrointestinal events occur during puberty and thus we speculate that the high level of protein expression may be hormonally mediated.

Animals↗

[Post-appendectomy fistulas of the cecum. Apropos of 22 cases].

Appendicitis, usually a benign disease, can have its prognosis worsened in case of postoperative fistula. The latter occurs rarely after open appendectomy (0.133%), but accounts for 10% of the morbidity rate. The authors reviewed 22 cases of these fistulas, treated during a 24-year period (January 1970 to December 1993). The aim of these retrospective study was to precise their clinical features, to evaluate paraclinical examinations in diagnosing these complications and to give guidelines for their treatment. Fistulas occurred at day 14 in the postoperative course. In 21 case, appendicitis was severe (suppurative, gangrenous or perforated) or appendectomy quoted as technically difficult. Location of the appendix was atypical in 7 cases. Drainage of the site was performed in 17 cases at the time of appendectomy. Diagnosis was made on the aspect of the drainage fluid in 14 cases. Diagnosis workup of the fistula associated plain abdominal radiograph and abdominal ultrasonography (n = 22). Fistulography (n = 6) confirmed the clinical diagnosis of fistula, showing the leaking in all cases. Medical treatment was attempted first in 14 cases and was successful in 11 cases with a healing time from 13 to 72 days. Surgical treatment (open drainage of the site) was attempted first in 11 cases, and was mandatory in 3 other cases because of medical treatment failure: one patient died and 5 patients underwent re-operation (right colectomy in 3 cases, bypass in 1 case and re-drainage in 1 case). Fistulography in our experience, is highly reliable and is considered to be a great assistance in management of these fistulas. Medical treatment remains the best initial treatment modality. Surgery must be contemplated in case of established external fistulas, and of purulent or faecal fistulas. Nevertheless, prognosis remains poor (50% re-operation rate).

Adolescent↗