Evidence for unique distribution of Kimmelstiel-Wilson nodules in glomeruli.

Different distributions of segmental lesions within glomeruli correspond to different pathogenetic mechanisms. A graphic method of analysis of the position of segmental lesions was applied to 106 Kimmelstiel-Wilson nodules in 10 renal biopsies from patients with diabetic glomerulonephropathy, 4 with IDDM and 6 with NIDDM. The nodules were randomly distributed in a horseshoe-shaped area corresponding to the peripheral or intralobular mesangium. This distribution was different from that of segmental lesions studied previously in the glomerular tip lesion, in vasculitic-type glomerulonephritis, and in hyperfiltration associated with reduced renal mass. Our finding is consistent with ideas that Kimmelstiel-Wilson nodules have a distinct pathogenesis not related to hyperfiltration or any other process previously investigated as a cause of characteristic distribution of segmental lesions.

Campylobacter-like organisms and heterotopic gastric mucosa in Meckel's diverticula.

To assess the possibility that Campylobacter pylori might colonise heterotopic gastric mucosa a detailed histological review of 69 cases of Meckel's diverticula resected over 17 years was undertaken. Twenty three were resected incidentally while 46 were excised as the suspected cause of symptoms. Gastric mucosa was found in 13 diverticula (19%), 10 from the symptomatic group and three from the incidental cases, of which eight showed active gastritis affecting the heterotopic mucosa. Specific staining showed spiral bacteria with the typical morphology of C pylori adherent to gastric mucosa in four of the diverticula showing active gastritis. Campylobacter-like organisms were not seen on normal heterotopic gastric mucosa or on adjacent intestinal epithelium. The findings show that Campylobacter-like organisms, identical in appearance, staining, and distribution with C pylori, colonise and possibly inflame heterotopic gastric mucosa in Meckel's diverticulum.

Expression of proliferating cell nuclear antigen (PCNA) in gastric carcinoma: no evidence for prognostic value.

It has been proposed that immunostaining with PC10, a monoclonal antibody against proliferating cell nuclear antigen (PCNA), is of prognostic value in gastric carcinoma. Gastric carcinomas from a series of 90 patients in whom survival data were known have been studied. There was no relation between the degree of PC10 immunostaining assessed semiquantitatively and survival.

Induction of cholangiocarcinoma in the Golden Syrian hamster using methylazoxymethyl acetate.

The Golden Syrian hamster, which has a bile acid profile similar to that of humans, is often used as an experimental model for cholangiocarcinoma. Unfortunately, most chemical carcinogens result in other tumour types also being induced which can be disadvantageous. In the present study, we describe the development of cholangiocarcinoma associated with precursor lesions of bile duct proliferation and dysplasia which occurred following a single i.v. dose of methylazoxymethyl acetate (10, 20 or 40 mg/kg body weight). Moreover, no other tumours were induced. This model may, therefore, prove useful in investigating the steps involved in the carcinogenesis of cholangiocarcinoma.

Use of the OM-11-906 monoclonal antibody for determining p62 c-myc expression by flow cytometry in relation to prognosis in colorectal cancer.

The expression of the c-myc protein product (p62 c-myc) and deoxyribonucleic acid (DNA) ploidy status was determined by a flow cytometric technique in 83 patients with colorectal cancer followed up for a median of 30 months (range 6-60 months). The OM-11-906 antibody, used to detect p62 c-myc, revealed a 62 kDa and 45 kDa band on Western blots in tumours. Correlation of quantitative dot blotting of tumour mRNA to flow cytometric p62 c-myc expression was good (r = 0.87, P less than 0.01). Levels of p62 c-myc varied in colorectal cancer and low levels (less than 20 fluorescein units) correlated with improved survival (log rank chi 2 = 4.69, df = 1, P = 0.03), and this was a better prognostic index than DNA ploidy (log rank analysis chi 2 = 2.38, df = 1, P less than 0.1). Although expression of the c-myc gene was found, using the OM-11-906 antibody, to be a prognostic feature in colorectal cancer, these and other results need to be interpreted with caution given the presence of two protein bands by Western blotting.

Comparability of hamster with human faecal unconjugated bile acids in a model of colorectal cancer.

The relationship between experimental colorectal carcinogenesis and bile acids has usually been investigated in the rat, a species with a markedly different bile acid profile from man. In this study, we show that the hamster faecal bile acid profile is similar to that in man. Rectal cancer was induced in hamsters using twice weekly instillations of N-methyl-N-nitro-N-nitrosoguanidine (MNNG) for 4 weeks at doses of 1-8 mg kg-1. The medcian (range) faecal bile acid concentrations of tumour-bearing hamsters (0.52, 0.46-0.84 mumoles g-1 faeces) was reduced compared to controls (1.08, 0.95-1.65, mumoles g-1) and non-tumour bearing MNNG treated hamsters (1.18, 0.64-1.42 mumoles g-1), largely due to a decrease in cholic acid derivatives (all p less than 0.05) at least). This model may be more suitable for studying the relationship between colorectal cancer and bile acids.

Vasculitis of the gall bladder in rheumatoid arthritis and systemic lupus erythematosus.

Three cases of acute cholecystitis due to vasculitis of the gall bladder are described; one in a patient with rheumatoid arthritis, and two in association with systemic lupus erythematosus.

Intestinal-type gastric carcinoma and colonic carcinoma: a common pathogenesis?

Intestinal-type gastric carcinoma and colorectal carcinoma have similar histological appearances. In the early stages of both disorders, undifferentiated cells capable of division are found on mucosal surfaces. These undifferentiated surface cells may be important in the pathogenesis of both neoplasms.

Mucosal mast cells in reflux gastritis and chronic (type B) gastritis.

The histological features that characterize alkaline reflux gastritis are typical of the histamine-mediated response to tissue injury. We have investigated this in nine patients with symptomatic reflux gastritis following partial gastrectomy for duodenal ulcer by determining the gastric mucosal mast cell count before and after Roux-en-Y biliary diversion. Following diversion, the histological picture changed from that of reflux gastritis to type B chronic gastritis in all cases. The mean mucosal mast cell count in all patients was 47.57/mm2 before diversion and 123.33/mm2 after diversion (P less than 0.05). Analysis of the paired data, in which eight out of nine patients showed a rise in mucosal mast cell numbers following bile diversion, also showed a significant difference before and after surgery (P less than 0.01). The gastric mucosal mast cell count is significantly less in reflux gastritis than in type B chronic gastritis. This is most likely to be due to increased degranulation, which would explain why striking vascular changes occur in the absence of inflammatory cell infiltration in reflux gastritis.

Analysis of the position of segmental lesions in glomeruli in vasculitic-type glomerulonephritis and other disorders.

A method was developed of plotting the position of segmental lesions in glomeruli on histological sections of kidney. Using a Leitz Imagan semi-automatic image analyser, the outline of lesions was traced, as was the outline of Bowman's capsule. The centre of gravity of a lesion, computed by the image analyser, was plotted with reference to the line through the hilum and the centre of gravity of the glomerulus, by taking its angle to that line and its proportional distance between that line and Bowman's capsule. Points representing all lesions were transferred onto a circle graphically representing a glomerulus. Lesions in 11 renal biopsies with the glomerular tip lesion were clustered at the tubular origin. Lesions in four necropsy kidneys from patients with one kidney were clustered at both the vascular pole and the tubular origin. Lesions in 13 renal biopsies with acute vasculitic-type glomerulonephritis were shown to be randomly scattered by nearest-neighbour analysis, after allowance had been made for an edge effect due to the method of plotting lesions and for an area where the arterioles passed through Bowman's capsule. Scientific analysis of the position of segmental lesions is possible and has confirmed previous suggestions that there are at least three general sites in which these lesions can be distributed in glomeruli: at the tip, at the vascular pole, and randomly.

Determinants of glomerular cross-sectional area.

A method of measurement of glomerular cross-sectional area was applied to 267 renal biopsies from 19 groups of patients with well-defined pathological and clinical conditions. There was a correlation between the mean glomerular area for each group and the percentage of global sclerosis in each group. A few groups had glomeruli that were larger than would be expected from their percentage of global sclerosis, probably due to cellular proliferation and/or infiltration. A few groups had glomeruli that were smaller than would be expected from their percentage of global sclerosis, probably due to ischaemic shrinkage. These observations indicate that as well as the known influence of body size on the glomerular area, the number of functioning glomeruli in the body has an important effect on the glomerular area.

Comparison of size of juxtamedullary and outer cortical glomeruli in normal adult kidney.

Abnormally large glomeruli are susceptible to hyperfiltration-associated sclerosis. We used an established morphometric method to test the general belief that juxtamedullary glomeruli are larger than those in the outer cortex, in a population with no clinical or pathological evidence of renal disease. Overall, juxtamedullary glomeruli were significantly larger, but this varied according to the amount of global glomerulosclerosis present. Global sclerosis increased with age, particularly in the outer cortex, and the ratio of juxtamedullary to outer cortical glomerular size showed a positive correlation with overall, and outer cortical, global sclerosis. Thus in the truly normal adult kidney, juxtamedullary glomeruli are not significantly larger than outer cortical glomeruli. However, global sclerosis increases with age and is most marked in the outer cortex, and this leads to compensatory enlargement of predominantly the juxtamedullary glomeruli. These findings suggest that in single kidneys, or in conditions characterised by ischaemic glomerulosclerosis such as hypertension, morphological changes related to hyperfiltration may appear first, and therefore become most severe, in juxtamedullary glomeruli.

Undifferentiated columnar cells in colorectal adenomas and familial adenomatous polyposis.

We have observed and defined morphometrically and histochemically groups of undifferentiated columnar cells within the surface epithelium in colorectal mucosa. They were present within both non-polypoid and polypoid mucosa in familial adenomatous polyposis, and within non-hereditary adenomatous polyps of the colon and rectum. The cells show some evidence of proliferative activity and appear similar to cells previously described in the stomach which were proposed as precursors to type 3 sulphomucin-secreting intestinal metaplasia in atrophic gastritis. To our knowledge, these observations have not been previously described. It is possible that the cells represent the cellular basis of the shift in the proliferative zone from the normal site at the crypt base to the colorectal mucosal surface, which is known to precede adenomatous polyp formation. The cells may therefore be involved in the early stages of colorectal adenoma formation.

Undifferentiated columnar cells on the gastric interfoveolar crest: a previously undescribed observation.

We have observed and defined morphometrically and histochemically an entity composed of groups of undifferentiated columnar cells on the interfoveolar crest of gastric mucosa. These cells are clearly distinct from either normal foveolar cells or regenerative epithelial cells associated with ulcer healing. They show a close association with atrophic gastritis, particularly in the presence of type 3 sulphomucin-secreting intestinal metaplasia. We have termed this the gastric tip lesion since it is observed only on the tips of the mucosal folds. This has not been described previously. We propose that these cells are the precursors of type 3 intestinal metaplasia and may also provide a link between this type of intestinal metaplasia and the intestinal variant of gastric adenocarcinoma.

The effect of routine endoscopy on the detection rate of T1 gastric cancer (early gastric cancer) in Birmingham.

The introduction of routine endoscopy facilities at the General Hospital, Birmingham has made no significant impact on the proportion of stage T1 or 'early' gastric cancers detected. Prior to this, T1 cancers comprised 2.8% of all tumors diagnosed, or 4.2% of resected cases. Following establishment of the service in 1974, 3.2% of all cases and 6.3% of those resected were stage T1 lesions. The clinical presentation reflected the high proportion of tumors associated with ulceration (67%). The accuracy rate for pre-operative diagnosis of a malignant lesion was barium meal 67%, cytology alone 73%, biopsy alone 80%, and cytology and biopsy in combination, repeated if suspicious, 100%. The crude survival rate at 5 years was 83.3% (age-adjusted 96%), and at 10 years 53.8%).

Assessment of glomerular size in renal biopsies including minimal change nephropathy and single kidneys.

A method of assessing glomerular size on sections of post-mortem kidney was adapted for use on needle biopsies of kidney. A semi-automatic image analyser was used to measure the cross-sectional area of the outline of Bowman's capsule on all glomeruli in renal biopsies. The mean of approximately the largest 25 per cent of areas was calculated. The method was used to compare glomeruli in 13 control patients without obvious structural abnormalities with those in 10 patients with a single kidney, 22 with minimal change nephropathy, and 20 with membranous nephropathy. Patients were at least 14 years old. Glomeruli in minimal change nephropathy were significantly smaller than those in all other groups. Glomeruli in single kidneys were significantly larger than those in all other groups. Glomeruli in membranous nephropathy were the same size as controls. Any differences between groups could not be explained by differences in body build. It is possible that in adults glomeruli in minimal change nephropathy are abnormally small. The method of assessing glomerular size can be used on renal biopsies as well as on sections of whole kidney.