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Summary. This study has examined the response of a rabbit model of inflammatory bowel disease to methylprednisolone. Colitis was induced in the colon of rabbits with 40 mg trinitrobenzenesulphonic acid in 25% ethanol (TNBS). The effect of methylprednisolone (0.5 mg/kg/day) on the development of colitis was determined at one week, by examining the colon’s macroscopic and microscopic appearance, the distribution of matrix metalloproteinases (MMPs) and by measuring eicosanoid production. Although there was no difference in the area of ulcerated colonic tissue in the treated and untreated TNBS animals, the increase in polymorphonuclear leucocytes was significantly reduced in TNBS rabbits given methylprednisolone. The only difference in the distribution of MMPs was a reduction in the number of polymorphonuclear leucocytes containing gelatinase B. The release of immunoreactive PGE2 and LTB4, but not 6-keto PGF1a, was increased in the TNBS animals and was unchanged by methylprednisolone. These results show that methylprednisolone does not modify the injury produced by TNBS in this model despite reducing the infiltration of polymorphonuclear leucocytes. Hence it suggests that these cells do not contribute to the injury observed, are not the source of the eicosanoids and that gelatinase B is not required in the healing process in this model.

Background Nearly 7 per cent of patients who undergo resection for colorectal cancer develop metachronous cancers several years later. A molecular marker that could identify patients susceptible to metachronous cancers would be of clinical importance. Methods Twenty-four colorectal cancers from 15 individuals with metachronous colorectal cancer were investigated for microsatellite instability at five loci by single stranded conformational polymorphism analysis. A control group of 14 colorectal cancers from individuals who had only developed one sporadic colorectal cancer each was analysed similarly. Results Microsatellite instability was demonstrated in 17 of 24 cancers from individuals with metachronous cancer compared with one of 14 cancers from individuals with a single colorectal cancer. Conclusion These results suggest that testing for microsatellite instability may be useful in recognizing patients at high risk of developing metachronous colorectal cancers.

SummaryAim - To correlate the magnetic resonance imaging signal changes observed during interstitial laser photocoagulation (ILP) therapy with histopatho-logical analysis of tissue necrosis. A 1.5T MR system was used. Lesions were produced with a diode laser (805 nm) in the liver of normal Wistar rats at laparotomy under general anaesthesia and imaged during treatment. Seventeen lesions were monitored with a T1-weighted spin echo (T1WSE) sequence, and 15 with a FLASH sequence. Treated tissue was removed and stained for NADPH-diaphorase to determine the extent of devitalization. Per-procedural T1WSE showed an expanding area of low signal which developed a high signal rim as ILP progressed. FLASH imaging showed an expanding area of low intensity which was replaced by a complex region of signal change as treatment progressed. Good imaging-histopathological correlation was shown: for T1WSE, r2=0.88 (P < 0.001) and for FLASH, r2=0.95 (P < 0.001). MR imaging during hepatic ILP accurately shows the extent of tis...

SummaryInterstitial laser photocoagulation (ILP) is currently limited by deficient per-procedural monitoring. The purpose of this study was to evaluate MR control of ILP of hepatic metastases. Twenty-two laser activations were used to treat eight metastases in seven patients under local anaesthesia and sedation. Laser energy was delivered via optical fibres positioned in the tumour under ultrasound guidance. T1-weighted FLASH and spin-echo sequences were used to monitor the procedure. Enhanced CT was performed at 24 h to assess thermal necrosis. FLASH imaging showed an enlarging area of signal change during ILP. The final extent of this correlated closely with the extent of tissue necrosis on CT. Spin-echo imaging was disappointing because of poor contrast between the treated tissue and normal liver/untreated tumour. Per-procedural MR imaging accurately and reliably depicts ILP-induced necrosis. MR control may permit more widespread application of ILP to the treatment of hepatic tumours.

FNA continues to play an important role in the management of patients with breast lesions. However, the reliability and efficiency of the FNA service depends heavily on the quality of the specimens. We have audited the rate of "inadequate FNAs' at intervals over the last 5 years and related our findings to the clinical expertise of the aspirator. We have also correlated the rate of inadequate FNAs with the percentage of patients who had an FNA preceding a definitive diagnosis of cancer. We report trends in the rate of inadequate samples, and subsequent diagnosis of cancer, over a 5-year period. The percentage of breast FNA samples reported as inadequate was 46.8% in 1988-89, falling to 20% in 1991-92 with the introduction of an FNA clinic, and rising to 30.6% in 1993. The rates of cancer following inadequate FNA were 15.7%, 16.1% and 4.2%, respectively, and the percentage of patients with cancer having a preceding inadequate FNA were 37.5%, 13.2% and 7.1%. Possible explanations for the apparent paradox between increasing numbers of inadequate FNA specimens and a falling breast cancer rate are discussed.

Objective To determine whether the use of gemeprost is associated with histological changes in the second trimester fetus. Setting Histopathology department of a university hospital. Design Retrospective comparison of histological features in fetuses aborted following maternal administration of gemeprost, with those in fetuses after spontaneous miscarriage. Outcome measures Degree of tissue fragmentation; other histological abnormalities. Results Significantly greater fragmentation of the liver was found in fetuses exposed to gemeprost (P= 0–046). Nonsignificant effects were found for brain (P= 0.082) and heart (P= 0.183), and no effect was seen on the kidney, adrenal and lung. No other significant histological differences were found between the two groups. Conclusions This study is the first to document an effect of gemeprost on the fetus, but confirmation is required in further studies. Other implications are discussed.

Lactase activity is present at high levels in the small intestine of some human adults and not others. This is due to a genetically determined polymorphism which affects the developmental regulation of the expression of the lactase gene. This polymorphism is of considerable interest in relation to cultural differences in nutrition but despite exhaustive studies, the molecular basis has not yet been found. It has not even been shown whether the sequence differences reside within or adjacent to the lactase gene itself or in a trans-acting factor. We have therefore exploited known DNA 'marker' polymorphisms within the exons of the lactase gene to examine the expression of the individual lactase mRNA transcripts from persistent and non-persistent individuals in order to determine whether the regulation is in cis or trans. Our results show that in certain lactase persistent individuals one allele of the lactase gene is expressed at much lower levels than the other and these individuals tend to have intermediate lactase activities. It is proposed that these people are heterozygous for the lactase persistence and non-persistence alleles and that this means that the nucleotide substitutions responsible for the lactase persistence/non-persistence polymorphism are cis-acting. This narrows down considerably the area of the genome that needs to be searched for the relevant sequence differences.

It is important to establish the cause of fetal and perinatal deaths, and it seems plausible that postmortem examinations that are less invasive than a full autopsy might overcome reluctance on the part of clinicians and parents. Reports from the 1990s suggest that postmortem magnetic resonance imaging (MRI) compares well with autopsy, and recent studies indicate that postmortem MRI is especially helpful in diagnosing central nervous system disorders. This study compared postmortem MRI of the renal tract with conventional autopsy findings in 37 cases. A standard head coil was used to record T2-weighted spin echo images in the coronal and sagittal planes. Autopsies were then performed by a perinatal pathologist who did not know the MRI findings. Renal tract abnormalities were detected in 5 of the 37 cases. There was a single false-positive MRI report. The MRI findings provided information that was considered to be as diagnostically useful as the autopsy findings. The cases presented a spectrum of congenital renal tract abnormalities. Postmortem MRI does not, of course, provide histological data, but imaging may be combined with needle biopsy. In 1 case, an image-directed needle biopsy confirmed the diagnosis of autosomal recessive polycystic kidney disease. Postmortem MRI is expected to become an important clinical resource, as limits of normality are defined at different gestational ages. It may prove helpful to combine MRI with image-guided biopsies and umbilical cord blood sampling to detect genetic and metabolic abnormalities.

Acute cerebral hypoxia-ischaemia, often due to birth asphyxia, is the major cause of perinatal brain injury. Phosphorus (31P) magnetic resonance spectroscopy (MRS) enables non-invasive monitoring of cerebral high-energy metabolites such as phosphocreatine (PCr) and nucleotide triphosphates (NTP; mainly adenosine triphosphate) and can evaluate hypoxic-ischaemic cerebral damage in the newbom.1,2 Following severe birth asphyxia, 31P spectra often appear normal for up to 24 h presumably due to apparent recovery of energy generation soon after the acute intrapartum insult. However, subsequent spectra often show reduced [ PCr] / [ inorganic phosphate (Pi)] : a measure of phosphorylation potential. In very severe cases, [NTP] eventually falls indicating impaired cerebral energy generation. This sequence of events has been termed “secondary energy failure” (SEF) .’ Proton (‘H) MRS has also been applied to studies of newborn brain enabling observation of choline-containing compounds (Cho) , total creatine (Cr) , N-acetylaspartate (Naa) and lactate (Lac) .3-5 Both 31P and ‘H spectra can be local&d to specific brain regions4s6 and metabolite concentrations can be quantitated.4~5~7*8 This report describes the early application of quantitative, local&d, ‘H and 31P MRS in severe perinatal hypoxic-ischaemic encephalopathy.

Summary Background At present necropsy is done in less than 60% of cases of perinatal death in the UK, despite the value of the procedure to the bereaved parents and their doctors. This low rate reflects the difficulty in discussing the examination during the acute distress after the death of a baby, and the personal and religious objections of many parents to necropsy. We compared post-mortem magnetic resonance imaging (MRI) of the fetus with internal perinatal necropsy to assess whether MRI examination is a feasible option for the 40% of cases where consent for necropsy is not given or requested. Methods We examined 20 stillborn, miscarried, or aborted fetuses by MRI and necropsy. Scanning was done in a 1·5 T system, in accordance with our protocol, immediately before necropsy. The MRI and necropsy findings were compared to assess how much diagnostic information was obtained by each technique. Findings In eight of the 20 cases the two examinations were in total agreement about the abnormalities present. In eight cases the necropsy provided more detailed information than MRI examination, but in four cases the MRI information was more extensive than that obtained at necropsy. In two of the latter cases, abnormalities of the central nervous system were seen only on MRI. Thus, in 12 (60%) of the 20 cases studied, MRI had equivalent or better diagnostic sensitivity than internal necropsy examination; in 18 (90%) of the 20 cases the two examinations were of similar clinical significance. Interpretation MRI of the stillborn or aborted fetus provides non-invasive access to information previously available only from necropsy.

Human dysplastic kidneys are developmental aberrations which are responsible for many of the very young children with chronic renal failure. They contain poorly differentiated metanephric cells in addition to metaplastic elements. We recently demonstrated that apoptosis was prominent in undifferentiated cells around dysplastic tubules (Winyard, P.J.D., J. Nauta, D.S. Lirenman, P. Hardman, V.R. Sams, R.A. Risdon, and A.S. Woolf. 1996. Kidney Int. 49:135-146), perhaps explaining the tendency of some of these organs to regress. In contrast, apoptosis was rare in dysplastic epithelia which are thought to be ureteric bud malformations. On occasion, these tubules form cysts which distend the abdominal cavity (the multicystic dysplastic kidney) and dysplastic kidneys may rarely become malignant. We now demonstrate that dysplastic tubules maintain a high rate of proliferation postnatally and that PAX2, a potentially oncogenic transcription factor, is expressed in these epithelia. In contrast, both cell proliferation and PAX2 are downregulated during normal maturation of human collecting ducts. We demonstrate that BCL2, a protein which prevents apoptosis in renal mesenchymal to epithelia] conversion, is expressed ectopically in dysplastic kidney epithelia. We propose that dysplastic cyst formation may be understood in terms of aberrant temporal and spatial expression of master genes which are tightly regulated in the normal program of human nephrogenesis.

Sixty one duodenal biopsy specimens were examined for the expression of lactase at the level of enzyme activity, protein, and messenger RNA. Of the 51 samples with normal villous architecture, 39 were lactase persistent, 11 were nonpersistent (adult type hypolactasia), and one was of indeterminate status. All the lactase persistent individuals showed high mRNA and a high level of the lactase protein as detected by sodium dodecyl sulphate polyacrylamide gel electrophoresis. All the 11 non-persistent individuals tested showed a low level of lactase protein. Nine of the 10 samples tested showed low mRNA and one high mRNA. These results suggest that the lactase persistence polymorphism is controlled at the level of the expression of the lactase gene, though there may be some heterogeneity of the lactase non-persistence phenotype.

A patient with a history of ovarian adenocarcinoma underwent further surgery because malignant cells were reported in peritoneal washings on two separate occasions. Subsequent laparotomy revealed an ectopic pancreas on the jejunum. Review of the peritoneal cytologies confirmed that the cells previously thought to be malignant were in fact consistent with cells detached from the ectopic pancreas.

Sir, King et al.’ reported in this journal transfusion of blood from one twin to the other in a dichorionic pregnancy without the oligohydramnios-polyhydramnios sequence. We have now seen a dichorionic twin pregnancy with the oligohydramnios-polyhydramnios sequence. A 34 year old woman with a previous obstetric history of six uneventful term pregnancies was referred at 18 weeks of gestation with a twin pregnancy because of oligohydramnios in one sac. On detailed ultrasound examination, oligohydramnios in the sac of fetus 1 with polyhydramnios in the sac of fetus 2 were noted. Biometry agreed with her menstrual dates and fetal anatomy and umbilical artery pulsatility index were normal in both babies. Twin

The heterogeneous nature of tumour antigen expression may require selection of monoclonal antibodies on an individual patient or tumour basis to allow adequate tumour localisation. Carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA) expression has not previously been compared in colorectal cancer patients. Sections of cancer (n = 52), adjacent normal colon (n = 45), synchronous adenomas (n = 11) and nodal metastases (n = 49) were examined by indirect immunoperoxidase staining in 51 consecutive patients with colorectal cancer using monoclonal antibodies to CEA and EMA. The percentage of cells with positive staining in the primary tumours was graded 1: less than 25%, 2: 25-49%, 3: 50-75%, 4 greater than 75%. All primary colorectal cancers expressed CEA and 43 of 52 expressed EMA (83%). Grading showed CEA greater than EMA in 39, equal in 11 and less in two. Well differentiated cancers were more frequently graded three or four for CEA staining (23 of 27) than moderately differentiated cancers (11 of 22) (p less than 0.01). Equivalent figures for EMA were four of 27 and three of 22 (not significant) (NS) although the majority (86%) were graded 1 and 2. Grade 1 CEA expression was found in six of 15 proximal and only two of 37 distal lesions (p less than 0.01, chi 2 test) while for EMA equivalent figures were three of 15 and six of 37 (NS). Nodal deposits all expressed CEA and 45 of 49 expressed EMA (92%); 29 of 45 normal colon sections showed CEA expression (64%) as did all adenomas. EMA was not expressed by normal colon or adenomas. These results suggest that EMA expression is more specific but less sensitive than CEA for colonic cancer and is independent of tumour differentiation and site. Thus selecting monoclonal antibodies to CEA or EMA based on tumour biopsies may allow improved tumour localisation for imaging or therapy in patents with colorectal cancer.