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Rabbit appendix: a site of development and selection of the B cell repertoire.

As early as 1963, it was proposed that the rabbit appendix was a homologue of the chicken bursa of Fabricius (ARCHER et al. 1963). The finding that the young rabbit appendix was thymus independent contributed to the concept of central primary lymphoid tissue. Today we know that appendix is a site that generates the high copy number primary repertoire through diversification of rearranged VH genes by gene conversion-like and somatic hypermutation mechanisms. Thus the appendix of young rabbits functions as a mammalian bursal equivalent. In the appendix, newly generated B cells also undergo selection processes involving self and foreign antigens and superantigens. Preferential expansion and survival of B cells in normal and mutant ali rabbits based on FR1 and FR3 expression may involve "superantigen"-like interactions with endogenous and exogenous ligands. One endogenous ligand appears to be CD5. Additional ligands may be produced by gut flora. Further studies in the rabbit model are needed to determine the fates of emigrants from primary GALT, their sites of postulated self-renewal in the periphery, and the nature of secondary diversification in secondary germinal centers where populations of B lymphocyte memory cells may develop. These data may also be helpful in understanding how the repertoire of human B cells is formed and how this repertoire might be manipulated for clinical benefit.

Animals↗

Germinal centres and the B cell system. IV. Functional characteristics of rabbit appendix germinal centre (-derived) cells.

Functional capacities of rabbit appendix germinal centre cells were tested in appendectomized, 450 rads X-irradiated rabbits, reconstituted with autologous appendix germinal centre cells, which are obtained by mechanical separation--"stripping"--of the appendix. For comparison, functional capacities of appendix germinal centre derived cells were tested in rabbits, 450 rads X-irradiated with the appendix shielded. In both types of experimental systems, slow restoration of primary IgM responsiveness to Salmonella Java paratyphi-B (PAR) was observed; in contrast, the capacity for memory cell production (of both mu and gamma-type) to PAR was restored very early in both systems. These results suggest germinal centres to be antigen dependent microenvironments for selective as well as non-selective amplification of immature B cells, which after subsequent maturation become part of the pool of either memory or virgin mature B cells respectively.

Animals↗

Adenocarcinoid of the appendix presenting as a disseminated ovarian carcinoma: report of a case.

The occurrence of disseminated tumors of the appendix is a rare event. Usually appendix tumors are very small, located on the inside of the appendix, and can be pathologically diagnosed. Adenocarcinoid is an uncommon variant of carcinoid tumors that usually arises in the appendix. This report describes a case of a primary adenocarcinoid of the appendix in a patient who was preoperatively diagnosed to have uterus myomatosus but was intraoperatively found to instead have disseminated ovarian carcinoma. This case demonstrates that the clinical picture can be misleading, and that surgeons therefore always have to wait for the final pathological report before making a final diagnosis.

Adult↗

MR imaging of the normal appendix in children.

Our objective was to assess the ability of MR imaging in the detection of the normal appendix, and to describe the MR appearance of the normal appendix. There were 15 healthy volunteers (11 girls, 4 boys; mean age 12.3 years) who underwent MR imaging on a 1.0-T unit. The imaging protocol included axial and coronal T2-weighted ultra turbo spin-echo (UTSE)-weighted images, axial T1-weighted turbo spin-echo (TSE) and coronal short tau inversion recovery (STIR)/TSE sequences. Confidence regarding the detection was scored from 1 (high confidence) to 3 (low confidence). Thickness was measured and MR appearance described. Clinical control after 2 weeks revealed no signs or symptoms of acute appendicitis. The normal appendix was seen in 86% on T2/UTSE-weighted images and in 73% on T1/TSE-weighted images and in none on STIR/TSE images. On axial T2/UTSE-weighted images, normal appendix had a hyperintense center and a hypointense wall, and was mostly hypointense on T1/TSE-weighted images, with a mean thickness of 4.5 mm. Magnetic resonance imaging seems to be an accurate method for the assessment of the normal appendix in children; thus, MR imaging might be an alternative to CT if US examinations are inconclusive.

Appendix↗

Noradrenergic sympathetic innervation of lymphoid tissue in the rabbit appendix: further evidence for a link between the nervous and immune systems.

The rabbit appendix, a region of gut with well organized zones of lymphoid tissue, was examined with the glyoxylic acid histofluorescence technique for the localization of noradrenergic fibers, with high performance liquid chromatography with electrochemical detection (LCEC) for the quantitation of norepinephrine and serotonin, with Bielshowski and Giemsa stains for additional information about neural supply, and with acetylcholinesterase histochemistry for the localization of this hydrolytic enzyme. Fluorescent plexuses entered the serosal surface of the appendix associated with blood vessels, traveled longitudinally inside the muscularis interna, mainly in association with blood vessels but adjacent to enteric smooth muscle, and branched into long, linear, varicose plexuses that ran inward in a radial orientation towards the lumen in the internodular septa. As these fibers approached the interdomal regions near the epithelial surface, they passed through thymus-dependent cell zones, and arborized extensively throughout the interdomal region. A high density of varicosities was found in the subepithelial region where immunoglobulin-secreting plasma cells are found. These varicosities were sparse at 21 days of age, but were increased in number at 42 days of age. They were even further increased in number and density in adults. These fibers were further identified with a Bielshowski silver stain, and also demonstrated acetylcholinesterase activity. The noradrenergic varicosities in the interdomal regions of the adult rabbit appendix were closely associated with numerous yellow fluorescent cells of 25-40 microns diameter, which sometimes demonstrated fine varicose processes. The adult rabbit appendix contained a moderate concentration of norepinephrine (163.0 +/- 22.9 ng/g wet weight) and a very high concentration of serotonin (3981 +/- 283 ng/g wet weight). Levels in neonates were considerably lower, suggesting that the yellow fluorescent cells may contain serotonin. Acetylcholinesterase was associated with neural fibers and with non-neural regions of the lymph nodules and the domes, perhaps playing a protective role for these regions of the cellular immune system. The rabbit appendix is a well organized region of lymphoid tissue with specific zones of noradrenergic innervation and possible "paraneuronal" activity, with a readily accessible lumen for the isolation and collections of secretions. We propose this model as an excellent structure for further exploration of interactions between the nervous and immune systems.

Acetylcholinesterase↗

Location of the appendix in the gravid patient: a re-evaluation of the established concept.

OBJECTIVES: To determine the anatomical location of the appendix, as it may change during pregnancy. METHODS: In this prospective study conducted from October 1995 to March 1999, 291 women of reproductive age were evaluated for appendix location. They were divided into three groups: group A, 165 women between 37 and 40 weeks of pregnancy who underwent elective cesarean delivery; group B, 26 women between 19 and 39 weeks of gestation with acute appendicitis who underwent appendectomy; and group C (the control group), 100 non-pregnant women with acute appendicitis who underwent appendectomy. Appendix location was considered normal within 2 cm of the McBurney point; otherwise, it was considered to be a position change. RESULTS: In group A, 2 (15%) of 165 women and in group B, 6 (23%) of 26 women had a change in the position of the appendix. In the control group, 17% had change in position. There were no significant differences between group A and B compared with group C. In group B, no relation between height of fundus and point of tenderness was seen. CONCLUSION: Our study did not show that pregnancy changes the location of the appendix.

Adolescent↗

Atresia of the appendix.

A 4-day-old black male underwent laparotomy for intestinal obstruction. At surgery, multiple jejunal atresias (type IV) of the jejunum were detected. As an incidental finding, atresia of the appendix was also present. The jejunal atresia was repaired, and resection of the tip of the cecal pole and atretic appendix was performed. Gross and histological examination confirmed the presence of a type IV atresia of the jejunum and a cordlike (type II) atresia of the appendix with inflammatory changes in the tip of the appendix. The boy made an uneventful recovery. Examination of all organ systems did not show any associated findings, and the family history was unremarkable. To our best knowledge, this case represents the first case of atresia of the appendix described in the literature.

Appendix↗

Continent vesicostomy in the absence of the appendix: three methods in 16 children.

OBJECTIVES: To review our experience with three methods of continent vesicostomy and to examine the morbidity and long-term outcome of each method. In the absence of an appendix, the surgical options for constructing continent vesicostomies include the use of the ureter, retubularized ileum, or stomach, a Benchekroun valve, or creation of a continent stoma from the reservoir itself. METHODS: Between 1984 and 1999, 16 children, 14 with neurogenic bladder, 1 with cloacal malformation, and 1 with valve bladder, required access to their continent reservoir other than the urethra. The appendix was unavailable in all, either because it had been removed surgically at an earlier date or it had been used for an antegrade continent enema procedure. Eighteen continent vesicostomies were performed in 16 children. In 5 children, a Benchekroun valve was constructed. Two were subsequently replaced by tapered small bowel. In 7 children, a segment of small bowel was harvested, retubularized, and reimplanted in the reservoir in a submucosal or seromuscular tunnel. In 6 children, a flap of bowel forming the reservoir was raised, tubularized, and then a Nissen valve was constructed. RESULTS: The early results of the Benchekroun valve were satisfactory; however, the results with long-term follow-up were disappointing because 4 of 5 children developed stomal stenoses and one subsequent valve perforation. One of the 5 children continued to do well 6 years postoperatively. The 7 children in whom a segment of small bowel was retubularized (Monti procedure) continued to do well and to catheterize their stomas without difficulty. At last follow-up, 1 child was awaiting collagen implant of her bladder neck for urinary incontinence. Five of the 6 children with a Nissen valve were doing well 1 to 8 years postoperatively. One child did well initially, but was lost to follow-up 1 year later. CONCLUSIONS: The appendix is the preferred conduit for a catheterizable stoma. In its absence, our experience with the Benchekroun valve was disappointing. The retubularized ileum provided an excellent and reliable alternative to the appendix and is preferable if the bladder capacity is marginal. The Nissen valve constructed out of the reservoir has the advantage of avoiding intraperitoneal dissection and the use of additional small bowel. The two latter methods appear to be reliable in the long-term and are viable options when the appendix is not available.

Adolescent↗

Ureteral substitution using the isolated interposed vermiform appendix in a patient with a single kidney and transitional cell carcinoma of the ureter.

A patient with a single kidney presented with ureteral obstruction caused by a combination of primary transitional cell carcinoma of the ureter and extrinsic involvement of the ureter by a second primary malignant retroperitoneal lymphadenopathy. Due to the complexity of the case, we chose to perform a partial ureterectomy and used a method of ureteral substitution using the interposed vermiform appendix in combination with a psoas hitch. Application of the psoas hitch may allow the use of the appendix in most cases in which ureteral substitution becomes necessary. Antireflux mechanism is easily achieved with the appendix using the split cuff nipple technique. Finally, the use of the appendix allows complete retroperitonealization of the anastomoses to both ureter and bladder. We anticipate that the appendix will be used more commonly in the future as a ureteral substitute as more urologists become more comfortable with it through its use in various reconstructive procedures.

Aged↗

A morphological and immunohistological study of the human and rabbit appendix for comparison with the avian bursa.

Diversification of the primary antibody repertoire occurs in young rabbit appendix. As a prelude to molecular investigation of whether human appendix has a similar role, we compared the lymphoid morphology and distribution of common B- and T-cell subsets in frozen and/or paraffin-embedded normal appendix specimens at various ages. IgA, IgM and IgG staining patterns were similar in frozen human and rabbit appendices. The elongated follicles of the young human and rabbit appendices regressed with age to resemble Peyer's patches. Although similar in morphology to the bursa, human and rabbit appendix follicles differ in that they do not involute completely with age and contain significant numbers of germinal center (GC) T cells although the number is low early in life. If the human appendix functions as a primary lymphoid organ, it may occur during the first few months of age when the GC T-cell density is low.

ADP-ribosyl Cyclase↗

[Diverticula of the appendix and their complications: value of sonography (review of 21 cases)].

PURPOSE: Diverticulosis is defined by the presence of diverticula along any segment of the GI tract. Diverticulosis and its associated complications may involve the appendix. The imaging and histological findings of 21 cases of diverticulitis of the appendix are reviewed. MATERIALS AND METHODS: Sonography, because of its high spatial resolution, is an ideal imaging technique to diagnose diverticulitis of the appendix. RESULTS: Similar to diverticulosis of the large bowel, diverticula of the appendix correspond to pseudo-diverticula composed of mucosa and sub mucosa herniating through the muscular layer. Chronic inflammatory changes affect the surrounding appendicular wall, as confirmed by histological examination. Clinical symptoms range from chronic right lower quadrant abdominal pain to acute appendicitis and even peritonitis. CONCLUSION: Based on this retrospective analysis of 21 cases, it is possible to describe the specific and sensitive imaging findings for diagnosis of simple and complicated forms of diverticulitis of the appendix. Surgery is the treatment of choice because of the high risk of perforation.

Appendix↗

Histological and immunological features of appendix in patients with ulcerative colitis.

Patients with ulcerative colitis (UC) have a less frequent prior history of appendectomy than the general population. The aim of the present investigation was to elucidate histological and immunological characteristics of the appendix in UC and to assess the effect of appendectomy on the disease. Nine subjects with mildly active UC were treated by surgical appendectomy. In four subjects, the histological findings of the appendix were compatible with ulcerative appendicitis. CD3+CD4+CD25+, CD3+CD4+CD45RO+, and CD3+CD8+CD45RO+ appendiceal mononuclear cells were significantly higher in UC than in acute appendicitis and in normal appendix. There was a trend towards higher mRNA transcripts of IFN-gamma in the appendix of UC than those in other two groups. Clinical activity index decreased significantly four weeks after the appendectomy, although the effect was transient. The appendix is a site of involvement in UC, where mononuclear cells are presumed to be at a state of basal activation.

Adult↗

Conservative management of appendix mass in children.

BACKGROUND: The management of an appendix mass in children is controversial. An experience of conservative management of appendix masses in a paediatric population over the last 19 years is reviewed. METHODS: The medical records of all children who presented with an appendix mass to one of three children's hospitals between 1982 and 2000 were reviewed. In that interval 427 children with a mean age of 7.3 years (range from 2 months to 18 years) presented with an appendix mass. Sixteen children had an immediate appendicectomy. The remaining 411 children were treated conservatively by close observation and antibiotics, with intravenous fluids and nasogastric suction if required. Once the child was well enough for discharge home, elective appendicectomy was booked for 4-6 weeks later. RESULTS: Three hundred and forty-six (84.2 per cent) of the children responded to initial conservative management and were discharged after a median stay of 6 (range 3-24) days. The children returned 4-6 weeks later for elective appendicectomy. The complication rate for elective appendicectomy was 2.3 per cent (eight patients). Those who had an uncomplicated elective appendicectomy had a median hospital stay of 3 (range 1-6) days. Histological examination demonstrated acute or subacute inflammation in 50.8 per cent of appendices removed at elective appendicectomy. CONCLUSION: Non-operative management of an appendix mass followed by elective appendicectomy is a safe and effective method of management.

Adolescent↗

Primary T-cell non-Hodgkin's malignant lymphoma of the appendix.

A case of primary T-cell lymphoma of the appendix in an 84-year-old female was reported. Appendectomy was performed as a result of the clinical diagnosis of acute appendicitis, due to the rebound tenderness of McBurney's point and thickness of the appendix wall as determined from ultra echo sonograph. Grossly, the surgical resected appendix did not have a dominant inflammatory appearance, therefore a tumor was suspected. Microscopic examination showed diffused proliferation of large and medium size lymphoma cells. Immunohistochemical examination further revealed that the lymphoma cells were positive for T-cell markers. To ensure this was a T-cell lymphoma, molecular examination was performed using paraffin-embedded tissue sections, since T-cell lymphoma of the appendix is extremely rare. Polymerase chain reaction (PCR) single-strand conformation polymorphism (SSCP) analysis demonstrated monoclonal T-cell receptor gene rearrangement. T-cell-rich B-cell lymphoma was excluded. To our knowledge, this is the first reported case of primary T-cell lymphoma of the appendix. PCR-SSCP analysis in paraffin-embedded tissue section was very useful in the diagnosis of lymphoma cell monoclonality.

Aged↗

Neutrophil count in the normal appendix and early appendicitis: diagnostic index of real acute inflammation.

It is generally accepted that the uninflammed appendix does not contain neutrophils. In view of that, we searched for the presence of neutrophils in 60 uninflammed appendectomies and compared the findings with the neutrophil count in 20 cases of early appendicitis. In the uninflammed appendix, the upper third of the mucosa showed a mean of 0.75 neutrophils (N) per 5 high power fields (HPF), 4.71 N/5 HPF in the middle third, and 2.70 N/5 HPF in the deep third. At the suberosa, a mean of 3.41 and 3.32 N per 10 post-capillary venules in respectively longitudinal and transverse sections of the organ were present. The number of neutrophils in the mucosa showed a positive correlation with the number in the subserosa. In the early appendicitis we observed a mean of 12.53 N/5 HPF in the upper third, 11.33 N/5 HPF in the middle third, and 13.0 N/5 HPF in the deep third; at the subserosa, a mean of 4.95 N/10 post-capillary venules in transverse sections and 4.45 N/10 post-capillary venules in longitudinal sections was observed. No positive correlation between N in the mucosa and subserosa was observed. The count of N in the mucosa of normal appendix and early appendicitis showed a significant difference (P <.005). We conclude that, although present, not more than 10 neutrophils/5 HPF are found in the mucosa of uninflammed appendixes. Neutrophil count in the lamina propria should support the diagnosis of "normal" appendix and could be an indicator for suspecting early appendicitis, preventing underdiagnosis.

Adolescent↗

Unusual duplication of appendix and cecum: extension of the Cave-Wallbridge classification.

Duplicated appendix has, to date, been classified into 3 types. The authors present a type of duplicated appendix not previously described. Surgical exploration was done in a 14-year-old girl who had an acute abdomen. Surgical exploration showed a duplicated appendix that arose from the normal appendix and ended in a thick-walled, inflamed, perforated muscular pouch. Duplicated appendix is a treatable condition that rarely occurs with colonic duplication and which should be considered in the differential diagnosis of lower abdominal pain.

Abdomen, Acute↗

Preferential expansion and survival of B lymphocytes based on VH framework 1 and framework 3 expression: "positive" selection in appendix of normal and VH-mutant rabbits.

B cells with a rearranged heavy-chain variable region VHa allotype-encoding VH1 gene segment predominate throughout the life of normal rabbits and appear to be the source of the majority of serum immunoglobulins, which thus bear VHa allotypes. The functional role(s) of these VH framework region (FR) allotypic structures has not been defined. We show here that B cells expressing surface immunoglobulin with VHa2 allotypic specificities are preferentially expanded and positively selected in the appendix of young rabbits. By flow cytometry, a higher proportion of a2+ B cells were progressing through the cell cycle (S/G2/M) compared to a2- B cells, most of which were in the G1/G0 phase of the cell cycle. The majority of appendix B cells in dark zones of germinal centers of normal 6-week-old rabbits were proliferating and very little apoptosis were observed. In contrast, in 6-week-old VH-mutant ali/ali rabbits, little cell proliferation and extensive apoptosis were observed. Nonetheless even in the absence of VH1, B cells with a2-like surface immunoglobulin had developed and expanded in the appendix of 11-week-old mutants. The numbers and tissue localization of B cells undergoing apoptosis then appeared similar to those found in 6-week-old normal appendix. Thus, B cells with immunoglobulin receptors lacking the VHa2 allotypic structures were less likely to undergo clonal expansion and maturation. These data suggest that "positive" selection of B lymphocytes through FR1 and FR3 VHa allotypic structures occurs during their development in the appendix.

Animals↗

Prediction of inflammation of the appendix at open and laparoscopic appendicectomy: findings and consequences.

OBJECTIVE: To evaluate the accuracy of operative assessment of the condition of the appendix during laparoscopic and open appendicectomy, and to assess whether a normal-looking appendix should be excised routinely during a laparoscopic operation. DESIGN: Prospective study. SETTING: District general hospital, UK. SUBJECTS: 387 patients who presented with signs and symptoms of appendicitis and underwent appendicectomy. INTERVENTION: 63 patients (16%) were operated on laparoscopically, of whom 48 were female. MAIN OUTCOME MEASURES: Correlation of operative with histological findings. RESULTS: The positive predictive value of operative assessment was increased during the laparoscopic procedure in both male (94.4% to 100%) and female (78% to 88%) patients. Of 21 female patients whose appendixes looked normal at laparoscopy, 5 had other conditions (appendixes normal on histological examination) and 4 were inflamed. CONCLUSION: In women of childbearing age a normal-looking appendix should be resected during laparoscopic appendicectomy unless another condition is obviously the cause of the signs and symptoms.

Adult↗