[Preliminary results of dynamic gracilloplasty in the treatment of fecal incontinence]. / Wstepne wyniki zastosowania dynamicznej graciloplastyki w leczeniu nietrzymania stolca.

UNLABELLED: Transposition of the gracilis muscle and its continuous electrical stimulation became a widely accepted method for treatment of patients with severe fecal incontinence. This method introduced to clinical practice by Baeten, Williams and Cavina has also been applied in total anorectal reconstruction following abdominoperineal rectum resection due to rectal cancer. This paper describes our (limited so far) experience with dynamic gracilloplasty procedure in the treatment of fecal incontinence in six patients with injury of anal sphincters. Complete preoperative work up was based on the clinical symptoms of fecal incontinence evaluated in detail according to Jorge and Wexner Incontinence Scoring System and the clinicomanometric continence criteria according to Holscheider scale. Anorectal manometry, transanal endosono-graphy, defecography and barostat study were performed in each patient before and following surgery. Dynamic gracilloplasty procedure was performed according to the modified Baeten procedure--as a one stage procedure. Medtronic equipment (IPG Pulse Generator 3023) was applied for gracilis stimulation. Short term program of fast-to-slow muscle conversion was applied starting from the second week following surgery. Patients were prospectively evaluated after surgery in terms of clinical symptoms and anorectal physiology. Complete fecal continence was achieved in all patients during the first month following surgery. There were no serious postoperative complications. It was shown during anorectal manometry that dynamic gracilloplsty could increase the anal sphincter pressure up to the range of healthy subjects, thus to prevent fecal leakage. The overall clinical and manometic results confirm the feasibility of anal dynamic gracilloplasty to restore fecal continence in patients with complete lost of sphincter function due to its traumatic injury or atresia. This technique deserves wider application also in Poland, since our initial results are encouraging. CONCLUSION: According to our limited experience dynamic gracilloplasty proved safe and effective procedure for the treatment end-stage fecal incontinence. Complete preoperative diagnostic work-up is essential for proper patients selection and surgical procedure should be performed in a specialised surgical center.

[Chronic inflammation of the colon: a diagnostic problem]. / Przewlekle odczyny zapalne jelita grubego--problem diagnostyczny.

Chronic inflammation of the colon and rectum with associated diarrhea has become more difficult to diagnose recently. Many etiological factors and different therapeutic outlines need to be carefully discussed and summarized. Based on most recent literature, authors present current data on etiology and specific (case-depended) diagnostic procedures in colitis and proctocolitis.

Experimental inflammatory bowel disease--role of T cells.

BACKGROUND: Our experiments were aimed to test: 1. which lymphocyte subpopulations participate in mouse colitis, produced by intrarectal (i.r.) deposition of trinitrobenzene sulphonic acid (TNBSA, TNP hapten); 2. the expression of cell adhesion molecules on lymphocytes draining the site of reaction; 3. the influence of mouse haplotype on the development of colitis. METHODS: CBA/J, BALB/c and C57BI/6 inbred and outbred Swiss Webster strains were used. Mesentheric lymph node (MLN) cells of immunized animals, unseparated or separated into CD4+, CD8+ or gammadelta+ and alphabeta+ T cell subpopulations or depleted of B lymphocytes, were transferred into recipients which were challenged i.r. with TNBSA. Inflammatory reaction in the colon was confirmed macro- and microscopically and by myeloperoxidase (MPO) level. MLN lymphocyte surface markers were tested cytofluorimetrically using appropriate antibodies. RESULTS: Sensitization with TNP results in chronic colitis (hapten dose-dependent colon weight gain and cellular infiltrate, significant increase of MPO level) only in CBA/J and BALB/c strains and can be adoptively transferred in a cell-dose dependent manner into syngeneic recipients by T alphabeta+ cells of both CD4+ and CD8+ subpopulations. T gammadelta+ cells were ineffective and B lymphocytes do not participate in the passive transfer reaction. In MLN the number of T lymphocytes positive for cell adhesion molecules particularly LPAM-1 (V-CAM1) and LPAM-2 increases significantly. CONCLUSIONS: Both CD4+ and CD8+ lymphocytes participate in the development of TNP-induced colitis. High MPO level may suggests that both Th1 and Th2 cells are involved. Colitis is accompanied by a significant accumulation in MLN of T lymphocytes positive for several cell surface adhesion molecules characteristic for memory T cells. Significant differences in susceptibility to develop colitis were found between different strains of mice.

Cross-reactivity of TNP immune effector T cells that mediate contact hypersensitivity and inflammatory bowel disease in the mouse.

BACKGROUND: Experiments were aimed to test the cross-reactivity of immune Th1 cells that mediate contact hypersensitivity (CHS) or inflammatory bowel disease (IBD) to TNP in the mouse. METHODS: CBA/J mice were immunized either epicutaneously or intrarectally with TNP and after appropriate time intervals were challenged with antigen in a crossed manner. The CHS reaction was measured by the ear swelling test. IBD was quantified by increase of colon weight and myeloperoxidase level. Both reactions were confirmed histologically. In passive-transfer experiments, mesenteric lymph node cells of animals sensitized intrarectally and peripheral lymph node and spleen cells of mice immunized epicutaneously were used. In some experiments, before being immunized mice were made either unresponsive to the TNP hapten by induction of suppressor T cells, or resistant to suppression after induction of upregulatory T cells. RESULTS: Irrespective of the mode of sensitization upon appropriate challenge with antigen all mice developed a good CHS reaction as well as significant IBD. This cross-reactivity could be passively transferred by immune cells. In mice in which antigen-specific down- or upregulatory cells were induced before sensitization both CHS and IBD to TNP were modulated accordingly. CONCLUSION: TNP hapten deposited on skin or on mucosal surfaces induces effector cells that recognize antigen independent of its tissue localization, and produce a local inflammatory reaction. TNP-specific up- and downregulatory cells, shown before to regulate the CHS reaction, similarly modulate the generation and development of hapten-induced IBD.

[Defense mechanisms in the peritoneum]. / Mechanizmy odpornosciowe otrzewnej.

There are many specialised defence mechanisms connected with immunity of peritoneal cavity. These are absorbtion of bacteria and their toxins from peritoneum, phagocytosis, opsonization, activation of the complement and separation of infection in the peritoneal cavity. A very important role in defence mechanisms of peritoneal cavity play GALT and PALT. Among many cells of the immune system mastocytes and gamma delta T cells have important role in induction and regulation of immune mechanisms in the peritoneal cavity. Lymphocytes T gamma delta release many cytokines and chemokines what allows them to play their protecting role during peritonitis. Released cytokines (especially IFN-gamma) activate macrophages to produce and secret many proinflammatory cytokines and factors. On the other hand mast cells play their role in defence of peritoneal cavity via TNF-alpha and histamine release and inhibition of fibrynolysis.

A topographic analysis of atrophic gastritis and stomach cancer risk. A clinicoepidemiological study in Poland.

The purpose of this cross-sectional study was to assess the relation between intestinal and diffuse stomach cancer at its various locations with topography of atrophic gastritis. The study population consisted of 3435 patients who reported over the period of 1991-1994 for the first time to gastroenterological outpatient clinics of 7 university medical centers in Poland. Among these subjects there were 131 histologically proved consecutive cases of gastric carcinoma. The reference group consisted of 1540 patients among whom endoscopic examination did not reveal peptic ulcers, polyps, deformations of antrum or bulbus duodenum and mucosa erosions. Gastroscopy on gastric cancer patients and the reference group was performed and biopsy specimens were obtained from the tumour and from the antrum and stomach corpus distant from the tumour. Among the gastric cancer cases there was a higher prevalence of atrophic gastritis in the intestinal than in the diffuse type. The highest prevalence of atrophic gastritis irrespective of its degree and stomach area was observed in the tumour-area of intestinal cancer located distally (78.9%), and the lowest in the tumour-free area in diffuse proximal cancer (18.5%). Prevalence of atrophic pangastritis (atrophic gastritis present both in the corpus and antrum) was also highest in intestinal distal cancer (69.2%) and lowest in diffuse proximal cancer (21.7%). The age-adjusted correlation coefficients between gastritis score in the tumour-area and tumour-free area were highly significant. It was shown that only atrophic pangastritis was significantly associated with gastric cancer irrespective of its histology and location (OR = 3.8, 95% CI:2.4-6.0), however, it was much stronger related to the intestinal gastric cancer (OR = 5.9, 95% CI: 3.1-11.0), than to the diffuse carcinoma (OR = 2.2, 95% CI: 1.1-4.3).

A clinico-epidemiological study on gastritis in gastric carcinoma and in non-cancerous gastric pathology in Poland.

To investigate the risk of gastric cancer development in subjects with atrophic and nonatrophic gastritis, we studied 221 consecutive gastric cancer patients and 7647 non-cancer subjects for whom endoscopic biopsy of the gastric mucosa was available. In gastritis patients, the relative risk (RR) estimates of gastric cancer were as follows: corpus atrophic gastritis RR = 8.7 (95% CI = 5.4-14.1), antral atrophic gastritis RR = 4.5 (2.4-8.1), chronic atrophic pangastritis RR = 7.6 (3.8-15.3), corpus nonatrophic gastritis RR = 1.6 (0.9-2.7), antral non-atrophic gastritis RR = 1.2 (0.7-2.3), and pangastritis RR = 1.3 (0.6-2.8). The latter was of borderline significance (p = 0.07). In peptic ulcer, a significant excess risk was calculated for subjects with either corpus atrophic gastritis (RR = 3.1 [2.5-3.9] or antral atrophic gastritis (RR = 3.5 [2.6-4.8]). For stomach polyps, the risk was significantly increased only in subjects with corpus atrophic gastritis (RR = 2.1 [1.3-3.5]). The risks for both peptic ulcer and polyps, however, were significantly increased in chronic atrophic pangastritis. A substantial excess risk of gastric cancer was found for atrophy in the corpus (RR = 20.9 [9.0-48.9]) and in the antrum (RR = 14.9 [5.3-41.9]). An increased risk of peptic ulcer was also confirmed in subjects with atrophy in the corpus (RR = 3.0 [1.3-6.9]) and in the antrum (RR = 4.9 [2.0-12.1]).

[Colitis in laboratory experimentation]. / Zapalenie jelita grubego w eksperymencie laboratoryjnym.

Immunological concept of pathogenesis of inflammatory bowel disease (ulcerative colitis and Crohn's disease) is presently most common but it's specific etiology is still unknown. Spontaneous manifestations of these disease in animal are very rare and ad adequate laboratory animal model is needed for research. In this review different animal models of colitis are present in chronological order, displaying the search for the highest similarity to the clinical colitis.

Different patterns of gamma delta and alpha beta T cell redistribution in the mouse after partial gastrectomy.

BACKGROUND: Stress, including surgical trauma, results in different dysfunctions of the body. In our former experiments on posttraumatic modification of immune response of gastrectomized mice we observed a significant suppression of contact sensitivity. This could be transferred by lymph nodes and spleen T lymphocytes of mice which underwent surgery. MATERIALS AND METHODS: We studied changes in gammadelta and alphabeta T cell numbers in peripheral blood, Peyer's patches, and mesenteric lymph nodes after partial gastrectomy (major operation) and after sham gastrectomy (laparotomy-minor operation) in mice. The number of gammadelta and alphabeta T cells was counted on the FACSTAR cell sorter before and 1, 2, 3, 7, and 14 days after surgery. RESULTS: In our observations there was a significant increase of percentage of gammadelta T cells both in Peyer's patches (1.9 +/- 0.5 to 10.5 +/- 0.3) and in mesenteric lymph nodes (2.7 +/- 0.7 to 8.8 +/- 3.5) on the third day after partial gastrectomy (546 and 322% of control values, respectively). In contrast in gastrectomized mice the number of alphabeta T cells in Peyer's patches (38.4 +/- 6.8 to 21.2 +/- 6.2) and lymph nodes (56.7 +/- 15 to 40.4 +/- 17) was decreased on day 3 (55 and 71% of control values, respectively). There was a decline in both alphabeta (18.1 +/- 8 to 8.2 +/- 1.7) and gammadelta (6.7 +/- 2.8 to 3.9 +/- 2) T cell numbers in peripheral blood on days 1, 3, and 7 (45 and 58% of normal values, respectively). Sham operation had no significant influence on alphabeta and gammadelta T cell numbers. We observed that after leg amputation the number of gammadelta T cells in mesenteric lymph nodes was significantly increased on day 3 (0.8 +/- 0.2 to 7.7 +/- 0.3), 770% of normal. In contrast to this, leg amputation had a negligible effect on T cell counts in Peyer's patches during all periods of observation. CONCLUSIONS: We suggest that the major surgical stress (partial gastrectomy) may disturb the normal cell traffic selectively with increased gammadelta T cell homing in intestinal Peyer's patches and lymph nodes (GALT) and with the cell displacement from peripheral blood to lymphatic organs. The severity and localization of stress may be crucial.

[Controlled clinical studies for topographic analysis of atrophic gastritis and stomach cancer]. / Badania kliniczno-kontrolne nad topografia zanikowego zapalenia blony sluzowej i rakiem zoladka.

The purpose of this cross-sectional study was to assess the relation between intestinal and diffuse stomach cancer at its various locations with topography of atrophic gastritis. The study population consisted of 3435 patients who reported over the period of 1991-94 for the first time to gastroenterological outpatient clinics of 7 university medical centers in Poland. Among these subjects there were 131 histologically proved consecutive cases of gastric carcinoma. The reference group consisted of 1540 patients among whom endoscopic examination did not reveal peptic ulcers, polyps, deformations of antrum or bulbus duodenum and mucosa erosions. Among the gastric cancer cases there was a higher prevalence of atrophic gastritis in the intestinal than in the diffuse type. The highest prevalence of atrophic gastritis irrespective of its degree and stomach area was observed in the tumour-area of intestinal cancer located distally (78.9%), and the lowest in the tumour-free area in diffuse proximal cancer (18.5%). Prevalence of atrophic pangastritis (atrophic gastritis present both in the corpus and antrum) was also highest in intestinal distal cancer (69.2%) and lowest in diffuse proximal cancer (21.7%). For other types of cancer the prevalence rates of atrophic pangastritis was 50.0% in intestinal proximal cancer and 37.5% in diffuse distal carcinoma. The age-adjusted correlation coefficients between gastritis score in the tumour-area and tumour-free area were highly significant. It was shown that only atrophic pangastritis was significantly associated with gastric cancer irrespective of its histology and location (OR = 3.8, 95% CI:2.4-6.0), however, it was much stronger related to the intestinal gastric cancer panga (OR = 5.9, 95% CI: 3.1-11.0), than to the diffuse carcinoma (OR = 2.2, 95% CI: 1.1-4.3).

[Clinical significance of heat shock proteins. Influence of heat shock proteins on the pathomechanism of selected diseases]. / Kliniczne znaczenie bialek szoku cieplnego. Udzial bialek szoku cieplnego w patomechanizmie rozwoju wybranych jednostek chorobowych.

The presentation shows the survey of diseases the pathogenesis of which might be connected with the existence of Heat Shock Proteins (HSPs). We discuss the data referring to the influence of the HSPs upon the occurrence and progression of the following diseases: systemic lupus erythematosus, reactive arthritis, rheumatoid arthritis, insulin dependent diabetes mellitus, schizophrenia and Alzheimer's disease. There is also indicated a possible activity of HSPs in the pathogenesis of neoplasia, organ ischaemia and inflammation or degeneration.

Sex differences in regulation of contact sensitivity reaction in mice. 1. Influence of sex on the generation of contrasuppressor and afferent suppressor cells.

It is well known that humoral and cell-mediated immune responses are better in females than in males. Females also develop autoimmunity more easily than males. Contact sensitivity, one of the forms of cell-mediated immunity, is controlled at the afferent and efferent phases by complex interactions of regulatory T cells. Our present experiments indicate that T suppressor afferent (Ts-aff) and T contrasuppressor cells (Tcs) are generated in the mouse in a sex-dependent fashion. These two types of regulatory cells are induced by antigen-antibody complexes containing various immunoglobulin isotypes. Females require fewer antigen (Ag)-IgG1 complexes to produce Tcs cells, but more Tcs cells after antigenic stimulation in females tips the balance toward better immune responsiveness. It remains to be established whether the peculiarities in generation of regulatory cells in female mice are relevant to the pathogenesis of autoimmune diseases which predominantly affect females.

Preferential induction of antigen-specific contrasuppressor T lymphocytes by trinitrophenyl (TNP)-substituted Langerhans cells.

We have tested the ability of trinitrophenyl (TNP)-labelled antigen-presenting cells (Langerhans cells (LC) and peritoneal macrophages (M phi)) administered intravenously to induce cells that mediate and regulate contact sensitivity. TNP-M phi fail to induce contrasuppressor cells (Tcs) but activate efferent T suppressor (Ts) cells. However, the activity of immune cells can be recovered after removal of Ly 2 Ts cells. In sharp contrast, TNP-substituted purified LC produced a significant contact sensitivity reaction, which is roughly equivalent to that achieved by skin sensitization with picryl chloride. Immune cells from these animals were relatively resistant to suppression by antigen-specific Ts cells, and we have found that their resistance is due to the presence of Ly 1, Vicia villosa lectin adherent, I-J+ cells. The Tcs cell induced by TNP-LC is indistinguishable by surface markers and function from Tcs cell found in mice injected with antigen-antibody complexes. Both these Tcs cells are capable of protecting immune cells from the effects of suppression by antigen-specific Ts cells if added in the proper sequence. Although they have identical surface phenotypes, it is not known at present whether or not Tcs cells induced by two different antigen presentations are identical. The possible reasons why LC are such potent inducers of contrasuppression are discussed.

Differential effect of experimental diabetes on the early and late phase of contact sensitivity reaction in mice.

Contact sensitization induces two different kinds of T cells (both Ly 1) that act in sequence to produce upon challenge with antigen a classical 24-hour local skin swelling reaction. One of these cells produces an antigen-specific factor. It has been suggested that it sensitizes mast cells, similar to IgE antibody, and causes them to release vasoactive amines in the presence of antigen. This results in an early (2-hour) swelling reaction. Increased vascular permeability facilitates the entry of the second, lymphokine-producing Ly 1 cell into the site of reaction to elicit the classical 24-hour delayed-type hypersensitivity reaction. In alloxan diabetic mice, contact sensitivity reactions are reduced significantly, and our experiments show that insulin deficiency affects only the activity of the late acting, lymphokine-producing cell and leaves the factor-producing cell responsible for the early swelling reaction unaffected. Our experiments demonstrate that insulin deficiency has different effects on distinct subpopulations of T lymphocytes.

Deficiency of contrasuppressor lymphocytes in alloxan-diabetic mice.

Ly 1 immune cells of alloxan diabetic mice are inferior to cells of normoglycemic PCl sensitized animals in transferring adoptive responses into recipients. A new regulatory activity, contrasuppression, that prevents suppressor cells from influencing activity of immune cells, has been recently described. Two types of Ly 1 contrasuppressor (Tcs) cells modulate contact sensitivity reactions in mice. A non-specific Tcs cell, which by itself has no immune activity, helps Ly 1 immune effector cells in adoptive transfer to bypass, in the recipient, the suppressor cell barrier. The antigen-specific Tcs cell induced by immune complexes makes Ly 1 effector cells resistant to specific suppression. Both Tcs cell, in contrast to Ly 1 effector cells, adhere to Vicia villosa lectin and can easily be separated (VV+ and VV-, respectively). Our experiments show that diabetic mice are deficient in nonspecific Tcs cells. The most important finding was that when immune Ly 1 cells of diabetic mice, which otherwise transfer little immunity, were injected together with Ly 1 VV+ cells of normoglycemic animals (these cells have no ability to transfer immunity whatsoever), the adoptive transfer was significantly augmented. We also demonstrate that diabetic mice are unable, upon appropriate immunization, to produce antigen-specific Tcs cells. Since a hypoinsulinemic environment abolishes the function of promiscuous Tcs cells and prevents the development of antigen-specific Tcs cells, this may suggest that contrasuppressor cells have insulin receptors which make them particularly sensitive to insulin deficiency.

Effect of surgical trauma (gastrectomy) on cell-mediated and humoral responses in mice.

Gastrectomy in mice affects the cell-mediated (CMI) and humoral immunity in a diverse fashion, such as CMI (contact sensitivity reaction) is severely impaired and antibody response is enhanced. Both effects are transient and disappear several days after surgery. While suppression of contact sensitivity is mediated by non-specific Ly 1-2+, L-J+ suppressor T cells generated by surgical stress, the mechanisms of enhancement of antibody response is unknown. We assume that the split unresponsiveness induced by surgical trauma has a clear survival advantage. Increased antibody production is the major defence mechanism against bacterial infections, while decrease of CMI prevents autoimmune response against altered (damaged) self structures.

Influence of anatomic localization and extent of surgical trauma on immune responses in mice.

The humoral immune response to SRBC and contact sensitivity (CS) reaction to picryl chloride and oxazolone was studied in traumatized mice (laparotomy, gastrectomy, leg amputation). While depression of CS was observed after leg amputation and gastrectomy, laparotomy had no effect. On the other hand, laparotomy and gastrectomy evoked stimulation of anti-SRBC antibody production, whereas leg amputation significantly reduced the humoral response. Results are discussed in relation to postulated role of trauma in the modulation of immune response regarding the anatomic localization and extent of surgical procedure.