Bacterial translocation has been consistently demonstrated in experimental models of obstructive jaundice. An important factor which promotes this phenomenon is physical injury of the intestinal mucosa. Some previous studies have presented suggestive evidence of this, following bile duct ligation. The aims of this study were to analyse objectively intestinal mucosal morphometric characteristics, to examine for evidence of bacterial translocation, and to assess enterocytes for ultrastructural abnormalities. Adult female Wistar rats were assigned to one of three groups: control (n=8), bile duct ligation (BDL; n=11), or sham operation (n=10). One week later, portal blood, mesenteric lymph nodes, liver, and spleen were harvested and cultured aerobically and anaerobically for evidence of bacterial translocation. Segments of jejunum, ileum, caecum, and large bowel were examined histologically, using light microscopy and morphometrically, using an image analysis system. Electron microscopy was performed on regions of the gastrointestinal tract where significant morphometric alterations had been identified. Significant bacterial translocation was identified following BDL (63. 6% BDL vs. 0% sham vs. 0% control, p<0.01, Fisher's exact test). There was a significant reduction in total mucosal thickness (standard error) [650 microm (23) BDL vs. 731 microm (27) sham vs. 744 microm (95) control] and villous height [451 microm (20) BDL vs. 515 microm (18) sham vs. 559 microm (79) control] in jaundiced animals, compared with sham-operated and control animals (p<0.02, Mann-Whitney U-test). Electron microscopy revealed oedematous change associated with mild inflammation, disruption of desmosomes, and the formation of lateral spaces between enterocytes. In addition, enterocytes showed vacuolation of their cytoplasm and mitochondrial swelling. Increased numbers of bacteria appeared to be attached to the mucosa. These data provide evidence of physical disruption of intestinal mucosa in jaundiced animals, most marked in the distal ileum. Significant bacterial translocation occurs following bile duct ligation and this supports the hypothesis of gut barrier dysfunction with obstructive jaundice.

SUMMARY Jejunal mucosal crypts were examined in jejunal biopsies from eight children with acute lvmphoblastic leukaemia who had recently received methotrexate treatment. By comparison with biopsies from children under investigation for suspected malabsorption crypt mitosis was significantly reduced and showed a negative correlation with the dose of methotrexate given prior to biopsy. The three major cell types were studied under light and transmission electron microscopy. Gut endocrine cells were unaffected by therapy and immature crypt enterocytes showed only patchy degenerative abnormalities. By contrast a number of Paneth cells showed striking structural alterations with vacuolar dilatation of the cytoplasm. The extent of this correlated with the time since methotrexate treatment rather than its dose and may have been a functional response rather than of a toxic nature.

Background-This report concerns a female patient now aged 24 years, diagnosed at the age of 7 years as suffering from chronic granulomatous disease. At age 20 she developed diarrhoea accompanied by rectal bleeding. Endoscopy showed extensive colitis. She failed to respond to medical treatment and underwent total colectomy two years later. Aims-To discuss the histological changes in the colon in chronic granulomatous disease.Results-There was extensive mucosal inflammation throughout colon and rectum resembling ulcerative colitis. In addition characteristic large pigmented macrophages were distributed in the basal mucosa and superficial submucosa. Similar cells accompanied by granulomata were present in mesenteric lymph nodes. Conclusions-Colitis is an unusual clinical manifestation of chronic granulomatous disease but the presence and characteristic distribution of such pigmented macrophages in colonic biopsy in children and young adults may suggest the diagnosis.

We report an unusual familial myopathy characterized morphologically by the presence of large tubular aggregates in all fibre types. Two patients, a father and daughter, presented with slowly progressive proximal weakness, limitation of eye movement, and Achilles tendon contractures. Serum creatine kinase was 5-10 times normal. Light microscopy revealed type I fibre predominance. Basophilic accumulations, which stained intensely with the NADH-TR reaction, were present in both fibre types. Electron microscopy revealed that these consisted of tightly packed parallel tubular arrays. These varied somewhat in their ultrastructural appearance and were classified accordingly as type I, II, and III tubular structures. The tubular aggregates appear to be derived from the sarcoplasmic reticulum. This report further supports the evidence of a distinct clinico-pathological entity of genetic origin.

The ultrastructural features of a case of disseminated malakoplakia are described and compared with available published cases. Generally macrophages were involved (although characteristic inclusions were seen in association with some plasma cells) and contained three types of cellular inclusions. These were (1) the phagolysosomes (2) and intermediate structure sharing features of the phagolysosome and the Michaelis-Gutmann (MG) body and (3) the MG body. All inclusions were delineated by unit membranes and their matrices (except those of large MG bodies) composed of membranous whorls and loops. It is suggested that these inclusions represent stages in the development of the MG body. Septate junctional complexes were observed between phagolysosomes and small MG bodies. These complexes may represent either a mechanism of organelle fusion or an abnormality of molecular organisation of the limiting unit membrane.