Search

RESUME La medecine francaise du XXI e siecle est legitimement satisfaite de ses etonnantes possibilites inconnues jusqu’alors, en matiere de diagnostic, traitement et communication internet. Mais paradoxalement, ces progres, qui auraient du favoriser une relation medecin-malade de qualite, ont souvent amene a delaisser la pratique clinique (ecoute, dialogue, examen clinique, etc.), pour privilegier la technologie et ses resultats. Dans l’interet des malades, l’Academie nationale de medecine tient a rappeler, c’est l’une de ses missions, qu’aujourd’hui comme hier, l’humanisme est consubstantiel a la medecine et que la pratique clinique ne peut etre opposee a la technologie, car elle en est indissociable.

RESUME L’inegale repartition de l’offre de soins sur le territoire national entraine des difficultes d’importance croissante. Se limitant a la Medecine generale qui est a la base du systeme sanitaire francais, la commission XVI de l’Academie nationale de medecine a tenu a completer les rapports qu’elle a deja consacres a ce sujet au cours des dernieres annees. Elle recommande d’abord une estimation plus precise de la demographie medicale et, surtout, la realisation reguliere d’etudes prospectives tenant compte, notamment, de la feminisation croissante du corps medical. Pour permettre un ajustement efficace du numerus clausus, ces enquetes prospectives doivent apporter des previsions au moins dix ans a l’avance. Par ailleurs, doivent etre formellement ecartees les diverses mesures contraignantes qui ont ete successivement envisagees. En revanche, plusieurs mesures incitatives pourraient apporter chacune une solution partielle. Il s’agit, par exemple, de la dissociation de la notion d’installation et de l’exercice professionnel et de l’obligation faite aux internes en Medecine generale d’effectuer leurs deux dernieres annees d’internat dans des regions sous dotees medicalement, ce qui ne peut que favoriser leur installation ulterieure dans ces regions.

Pinaverium bromide, a calcium channel blocker, is often used in the treatment of the irritable bowel syndrome. Colonie transit time (CTT) was evaluated by a simplified method using radiopaque markers in 19 healthy volunteers during 2 weeks of treatment with pinaverium bromide (50 mg three times a day) or placebo according to a double-blind crossover design. Pinaverium bromide significantly (p < .05) accelerated total CTT (30.2 ± 4.6 h, mean ± SE) compared with the placebo (38.2 ± 3.7 h). The decrease in CTT was related to accelerated transit in the descending and rectosigmoid areas of the colon (21 ± 4.5 vs. 30 ± 3.9 h, p < .05). CTT in the ascending colon was not significantly modified (9.2 ± 2.7 as compared with 9.5 ± 2.3 h). Stool frequency was not significantly increased by pinaverium bromide. These results suggest that pinaverium bromide might be effective in idiopathic constipation with slow CTT in the descending or rectosigmoid areas of the large bowel. The measurement of CTT is an easy and useful method for investigating the effects of drugs on colonie motility.

Are we going to change the way we practice medicine? There are two kinds of medical knowledge: one is impersonal and results from research based on scientific methodology and scientific reasoning; the other is personal and results from learning and apprenticeship with seniors and from individual experience. Evidence-based medicine (EBM) is a new approach to teaching the practice of medicine. Instead of using personal knowledge, intuition, unsystematic clinical experience, and pathophysiological reasoning, it stresses evidence from clinical research. With this new paradigm in mind, clinicians should regularly consult the original literature, critically appraise the methods and the results, and then apply to the patient the optimal knowledge they have at their disposal. This new approach to medicine is gaining worldwide adoption, even if it more or less strictly interpreted. In France, even the translation of the English word "evidence " is controversial. There are two different translations for EBM. The most common is "Medecine fondee sur les preuves", and the other is "Medecine factuelle". The French word "Preuves" is the literal translation of "evidence" Some people argue against this term because its meaning is ambiguous for two reasons: --it does not express the full meaning of the English word "evidence", --there is a fear that the epistemological significance of "preuves" could be misinterpreted, giving birth to legal quibbles. Some people prefer the term "meilleures donnees acquises de la science". Other problems are linguistic and organizational. How can a busy French-speaking practitioner locate, retrieve and critically appraisal original articles, most of which are in English, unless he/she has a library containing the combined international medical literature? French meta-analyses, systematic reviews and books dedicated to evidence-based subjects are alternative options. Even when these practical problems can be solved, the proper place of research-based evidence must be clarified. When evidence is lacking, practitioners have to rely on other forms of medical reasoning for their decisions. Moreover, decision-making is not automatic: in addition to taking scientific knowledge into consideration, each medical decision is the result of a series of judgments based on human and environmental factors.

Intracoronary brachytherapy aims at a reduction of in-stent restenosis by lessening neo-intimal proliferation. To assess its clinical potential, a systematic review of the literature indexed in the standard biomedical bibliographic databases selected eight prospective randomized clinical trials; seven of them, comparing coronary brachytherapy and non-treatment or placebo, have been included in the present meta-analysis. This analysis confirms the angiographic benefit of this procedure, as reported in the individual studies; it also shows, however an excess of clinical adverse effects not exhibited by any individual trial. Therefore, intracoronary brachytherapy cannot be recommended as routine practice, while one cannot rule out its interest in special situations.

Background Patients with ulcerative colitis are at risk of low bone mineral density (BMD). Proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis diminishes the risk of bone disease. The aims of this study were to assess the mechanism of low BMD and to measure bone density changes after IPAA. Methods Twenty patients with IPAA for ulcerative colitis, of mean(s.d.) age 38(9) (range 21-58) years, had measurements of lumbar spine and femoral neck BMD by dual energy X-ray absorptiometry, a mean(s.d.) 28(23) (range 3-84) months after proctocolectomy. Serum levels of calcium, phosphate, parathyroid hormone, osteocalcin and 25-hydroxy vitamin D were determined. Fifteen patients were followed for 28(12) (range 8-50) months. Results At baseline, six patients had spine BMD more than two standard deviations below the normal value, and three had vertebral crush fractures. Mean vitamin D values were normal and no patient had osteomalacia. BMD increased with time elapsed since IPAA (spine: r = 0.71, P = 0.005). During follow-up, mean(s.d.) changes in bone density were + 2.3(3.8) and + 2.1(5.6) per cent per year at the spine and femoral neck respectively. Conclusion These results suggest that in patients with IPAA for ulcerative colitis, low BMD is not associated with vitamin D malabsorption and may be reversible after surgery.

To assess the rate of bone loss in patients with inflammatory bowel disease, we prospectively studied 35 patients (17 women) aged 36 +/- 13 (range 17-60) years, 14 of whom had Crohn's disease and 21 with ulcerative colitis (including 12 with ileoanal anastomosis). Bone mineral density was measured by dual-energy X-ray absorptiometry at the lumbar spine and femoral neck. The follow-up was 19 +/- 8 months. During this period, 14 patients received oral steroids. Lumbar bone density changes expressed as a percentage per year were -3.1 +/- 4.9%, -6.4 +/- 7.5% and +2.0 +/- 4.0% in Crohn's disease and ulcerative colitis without and with ileoanal anastomosis respectively (p = 0.007). The same pattern was observed at the femoral neck. Mean annual lumbar bone density changes were -6.2 +/- 7.0% and +0.9 +/- 3.9% in patients with and without steroids during follow-up (p = 0.002). We conclude that patients with inflammatory bowel disease are at risk of lumbar and femoral bone loss. However, bone loss is not observed in patients with ileoanal anastomosis.

Endoscopic ultrasonography (EUS) and endoscopy were prospectively performed and compared to the histopathologic findings of the resection specimens in 24 patients with primary gastric lymphoma (PGL). On EUS, three types of PGL could be differentiated, a superficial type (n = 10), an infiltrating type (n = 12) and a tumorous type (n = 2). In the correct assessment of surface extension of the tumors, endoscopy and EUS agreed in 37.5% of cases and EUS showed more extensive disease than endoscopy in 58% of cases. However, in comparison to the resection specimens, EUS still underestimated the tumor surface extension in 37.5% of cases; this was mainly in low grade malignant PGL. The depth of tumor infiltration was correctly determined on EUS compared to the resection specimens in 91.5% of cases. Sensitivity, specificity and accuracy of diagnosing lymph node metastases were 100%, 80% and 83%, respectively. We conclude that EUS is a useful pre-therapeutic staging tool for primary gastric lymphoma but there remain some problems in determining the longitudinal and circular tumor spread in order to accurately guide the extent of gastric resection.

PAF-acether (PAF) is a phospholipid mediator with potent biological effects on the digestive tract. We report the presence of PAF in stool of patients with active Crohn's disease (39.1 +/- 13.5 ng/g of stool, mean +/- SEM, N = 19) and its absence in patients with irritable bowel syndrome with diarrhea and diarrhea with malabsorption. Fecal PAF acetylhydrolase activity was higher (P less than 0.04) in patients with Crohn's disease as compared to patients with irritable bowel syndrome with diarrhea and diarrhea with malabsorption. We also report a solid-phase extraction of fecal PAF using silica minicolumns, which yielded results highly correlated with those obtained with a high-performance liquid chromatography method (r = 0.86, P less than 0.001, N = 16). These findings may allow us to implicate PAF in the onset and perpetuation of digestive tract inflammatory symptoms observed during Crohn's disease. They would warrant to investigate the influence of various therapeutic agents, including PAF antagonists, on fecal PAF levels during inflammatory digestive ailments.

Recent studies have suggested that esophageal HPV infection could be a risk factor for esophageal squamous-cell carcinoma. The aims of our study were to assess the presence of HPV esophageal infection among French patients with esophageal squamous-cell carcinoma and to compare the prevalence of this infection among control patients exposed to similar known risk factors (alcohol and tobacco) and among non-exposed control patients. All patients had the following investigations: serum immunoglobulin level, T-lymphocyte subsets, cutaneous anergy test and endoscopy with biopsies from tumoral and normal areas. Three different methods were used for HPV-infection diagnosis: histological score, in situ hybridization intended for detection of HPV types 6, 11, 16, 18, 31 and 33, and dot blot intended for detection of HPV types 6/11 and 16/18. Five out of 12 patients with esophageal carcinoma had HPV esophageal infection. This infection did not result from impaired immune status. The most frequently observed types are HPV 16/18. None out of 17 exposed controls and only 1 out of 7 nonexposed controls had HPV esophageal infection (p less than 0.01). HPV infection may be implicated in the development of esophageal squamous-cell carcinoma in association with known risk factors.

Intracoronary brachytherapy aims at a reduction of in-stent restenosis by lessening neo-intimal proliferation. To assess its clinical potential, a systematic review of the literature indexed in the standard biomedical bibliographic databases selected eight prospective randomized clinical trials; seven of them, comparing coronary brachytherapy and non-treatment or placebo, have been included in the present meta-analysis. This analysis confirms the angiographic benefit of this procedure, as reported in the individual studies; it also shows, however an excess of clinical adverse effects not exhibited by any individual trial. Therefore, intracoronary brachytherapy cannot be recommended as routine practice, while one cannot rule out its interest in special situations.

Deep pelvic endometriosis may lead to severe pain, the treatment of which may require complete surgical resection of lesions. Digestive infiltration is a difficult therapeutic problem. Preoperative diagnosis is difficult and digestive infiltration may remain unknown with incomplete resection and sometimes repeated surgery. Both magnetic resonance imaging (MRI) and endoscopic ultrasonography are able to detect rectosigmoid infiltration but their usefulness in the preoperative staging is still to be evaluated. The aim of this work was to evaluate and compare both techniques in the preoperative detection of deep pelvic endometriosis, particularly digestive infiltration.From 1996 to 1998, 48 women with painful deep pelvic endometriosis had preoperative imaging exploration with endoscopic ultrasonography and MRI, and were operated on in order to attempt complete endometriosis resection. Patients were proposed for laparoscopic resection if endoscopic ultrasonography and/or MRI did not reveal digestive infiltration or for open resection if endoscopic ultrasonography and/or MRI were positive for digestive infiltration.Endoscopic ultrasonography and/or MRI led to suspicion of digestive endometriosis in 16 patients. Surgical resection was performed in 12 and digestive wall invasion was histologically demonstrated. At final follow-up, all patients had a dramatic decrease of their symptoms. The remaining 4 patients refused digestive resection and had only laparoscopic gynecologic resection. Infiltration although not histologically proven was very likely both on operative findings and clinical evolution. Digestive infiltration was preoperatively excluded in the 32 other patients. All had a laparoscopic treatment without digestive resection and pain diminished in all patients. In the 12 patients group who had digestive resection, digestive infiltration was correctly diagnosed by endoscopic ultrasonography in all cases (no false negative) whereas MRI, even with the use of endocoil antenna, led to correct diagnosis in 8 out of 12 cases. When endoscopic ultrasonography was negative for digestive infiltration, laparoscopic resection of lesions at surgery appeared complete in all cases. For the 16 patients with presumed digestive infiltration, sensitivity of endoscopic ultrasonography and MRI was 100 and 75% respectively, with a 100% specificity in both cases. MRI appeared very accurate for the detection of ovarian endometriotic locations. MRI was more sensitive but less specific than endoscopic ultrasonography for the diagnosis of isolated endometriotic recto-vaginal septum and utero-sacral ligaments lesions.Endoscopic ultrasonography was the best technique for the diagnosis of digestive endometriotic infiltration, which complicates the therapeutic strategy. MRI, however, allows more complete staging of other pelvic endometriotic lesions.

Cytogenetics studies have suggested that short arm deletion in chromosome 1 is involved in triggering colorectal tumor development. To elucidate the role of 1p under-representation in the tumoral process, we investigated by fluorescence in situ hybridization interphase cytogenetics, using simultaneously centromeric and p36 telomeric probes for chromosome 1, 27 primary adenocarcinomas, 5 metastases, 5 adenomas and as control 4 normal mucous membranes. The 1p under-representation in paradiploid tumoral cells, interpreted as a 1p deletion, was observed in 8/27 adenocarcinomas, 2/5 metastases and 3/5 adenomas. Thus, in diploid cells 1p deletion was observed in some tumors independently of the stage of the process. The 1p under-representation in total number of examined cells, i.e., diploid and aneuploid, was observed in 14/16 grade B1-B2 tumors, in 5/8 grade C1-C2 tumors, and all grade D tumors (3/3) and all metastases (5/5). There were no correlations with location or histological characteristics of cancers, gender or age of patients. These results show high frequency of 1p under-representation in intestinal tumors, and lead to separate the under-representation of 1p in diploid cells, which correspond to a 1p deletion probably implicated in the initiation of the process, from the under-representation in aneuploid cells, which mainly may be the consequence of complex rearrangements in relation to extension of the malignant process.

Nitric oxide synthase (NOS) activities are responsible for the enzymatic conversion of L-arginine into NO and L-citrulline. Relatively low amounts of NO are produced in intestinal epithelial cells or are released from nerve endings. The effects of NO production are related to the maintenance of epithelial integrity and permeability. A pathological role of an increased NO production has been suggested to play a role in models of experimental colitis. In humans, NOS activity in colon mucosa from patients with ulcerative colitis is clearly increased when compared with the activity of the control group. In contrast, an increase of NOS activity in the colon mucosa from patients with Crohn's disease remains controversial. In the present work, we have measured NOS activity in colon biopsies originating from the control group (n = 16), from patients with ulcerative colitis (n = 23) and Crohn's disease (n = 17) using the radiochemical method of the conversion of L-[guanido-14C] arginine into radioactive L-citrulline. In the control group, NOS activity was mainly of the inducible type (88% of total NOS activity) since it was characterised by its insensibility to the absence of calcium in the assay medium. In colon biopsies originating from patients with ulcerative colitis, inducible NOS activity was increased 3 fold (p < 0.005) and in patients with Crohn's disease, inducible NOS activity was increased 5 fold (p < 0.005). Correlations between NOS activity in colon biopsies and the intensity parameters of the disease i.e. Truelove index, endoscopic score and histological parameters were evidenced in patients with ulcerative colitis. In contrast, in patients with Crohn's disease, the high inducible NOS activity was not correlated with any intensity parameters of the disease. From these data, we concluded that although inducible NOS activity was increased several fold in colon biopsies originating from patients with both ulcerative colitis and Crohn's disease, a correlation between this activity and the severity of bowel inflammation was not found in either cases.

C 12 H 9 NO cristallise dans P1 avec a=8,837, b=7,910, c=6,903 A, α=108,2, β=77,7, γ=101,4°, Z=2; affinement jusqu'a R=0,054. L'analyse elementaire, le spectre de masse du compose et les spectres RMN a une et a deux dimensions sont en bon accord avec les resultats de l'analyse structurale, dans laquelle la molecule est consideree comme etant rigoureusement plane

This study was aimed at elucidating the relation between the cytogenetic characteristics and the invasive ability of two human colonic adenocarcinoma cells lines, HT29 and CaCO2. These two cell lines have very different tumorigenic and metastatic capacities after intrasplenic injection into nude mice: high for HT29 and relatively weak for CaCO2. At the time of injection, cytogenetic studies of the two cell lines revealed shared abnormalities: paratriploidy with seven common extra chromosomes or chromosome regions and specific particularities. In HT29 cells, we observed a large marker of unknown origin, an isochromosome i(11)(q10) and 5, 12, 13, 15, 19, and (19q+) supernumerary chromosomes, and, finally, the absence of one chromosome 16. In CaCO2 cells, we observed a chromosome 1-derived marker with q24-31 duplication, 12q and 16 supernumerary chromosomes, and a der(16) marker. The most striking difference between the karyotypes of these two cell lines concerned chromosome 16 (under- and overexpressed in HT29 and CaCO2 cells, respectively), overexpression of chromosomes 13, 15, and 19 in HT29 cells, and the relative loss of 12p in CaCO2 cells. Although some differences may be due to the intrinsic characteristics of the stem line, the establishment of specific cytogenetic abnormalities points out the role of many regions of the genome in tumorigenic and metastatic capacities of malignant cells.

Esophageal involvement is frequent in Down syndrome. We report a case of dysphagia in a 21-year-old patient with Down syndrome and repaired esophageal atresia. Radiology, endoscopy, and manometry showed typical features of achalasia. The patient was treated first by botulinum toxin injection and afterwards by Heller myotomy with good result. The role of motor disorders associated with esophageal atresia or with primary achalasia in this patient is discussed.

Peliosis hepatis is an uncommon liver condition characterized by blood-filled cavities. We report the CT, angiographic and MR features of a case of peliosis hepatis with no obvious etiology and spontaneously regressing hemorrhagic necrosis. Helical CT showed multiple peripheral low-density regions with foci of spontaneous high density suggesting the presence of blood component. On MR imaging, the multiple peripheral lesions were hypointense on T1-weighted and hyperdense on T2-weighted images, with bright foci on all sequences suggesting subacute blood. Angiography showed no evidence of tumor or vascular malformation; multiple nodular vascular lesions filling in the parenchymal phase and persisting in the venous phase suggested blood-filled cavities. Pathological examination showed blood-filled spaces with no endothelial lining, characteristic of the parenchymal type of peliosis. Knowledge of the imaging features of hemorrhagic necrosis due to peliosis hepatis is important since it can be responsive to antibiotic therapy. Furthermore, differentiating hemorrhagic necrosis from hepatic abscess avoids dangerous and sometimes fatal percutaneous drainage.

The pleiotropic cytokine leukemia inhibitory factor (LIF) possesses proinflammatory properties in common with tumor necrosis factor (TNF-alpha), interleukine (IL) -1 and -6, such as the induction of acute phase protein synthesis. LIF may have chemotactic activity through the induction of IL-8 production. LIF is produced by normal and tumoral cells and appears to facilitate in vivo rat colon carcinoma cells growth. Inflammatory bowel diseases, ulcerative colitis (UC) in particular, are histologically characterized by the infiltration of the colonic mucosa with activated neutrophils, macrophages and lymphocytes. Cytokines with their inflammatory as well as their regulatory activities may play a role in the perpetuation and possibly the initiation of inflammation in this disease and its local and/or systemic complications. Moreover, colorectal cancer is a late well identified complication in patients with long standing inflammatory bowel disease, UC in particular. Taken together, these results suggest that LIF could be involved in tumorigenic and/or metastatic processes of colorectal cells in UC patients. The aims of the present study was to quantify and to compare the colonic and systemic productions of LIF in UC patients. We showed for the first time in patients with UC, a high local production of LIF well correlated with IL-8 production. We also analyzed the effect of LIF on a human colon carcinoma cell line HT29. We demonstrated that LIF stimulated HT29 cell growth in a dose dependent-manner. These results suggest that LIF may play a critical role in the susceptibility of colonic host cells to tumor growth in patients with UC.

A radiological examination of the small bowel is often performed in case of gastrointestinal bleeding of obscure origin. More recently, push-type enteroscopy has been reported as a valuable tool in this indication. The purpose of this study was to compare the diagnosis efficiency of these two procedures.From February 1994 to February 1996, 40 patients (mean age: 52 years) with obscure gastrointestinal bleeding (iron-deficiency anemia without obvious cause of blood loss or malabsorption: n = 17; macroscopic gastrointestinal bleeding: n = 23) were examined by small bowel follow-through and push-type enteroscopy (jejunoscopy n = 19; double way examination n = 21). Each patient had negative upper and lower gastrointestinal tract endoscopies prior to small bowel examinations.Small bowel follow-through revealed only one lesion potentially responsible for blood loss (2.5%), corresponding to a jejunal leiomyoma. Push-type enteroscopy detected small bowel lesions potentially responsible for blood loss in 6 patients (15%). The lesions were located in the jejunum in 5 cases (arteriovenous malformations: n = 3; metastasis: n = 1; leiomyoma: n = 1), in the ileum in 1 case (leiomyoma). The efficiency of push-type enteroscopy for the detection of a small bowel lesion was of 22% in case of macroscopic bleeding and of 6% in case of iron-deficiency anemia. Push-type enteroscopy also revealed lesions previously undetected by gastroscopy or colonoscopy in 8 patients (20%).Push-type enteroscopy was more effective than small bowel follow-through to detect the origin of obscure gastrointestinal bleeding. Push-type enteroscopy revealed a cause of bleeding in 35% of patients, located in the small bowel in only 15% of the patients.

1. The toxic effects of nonsteroidal anti-inflammatory drugs for the lower gastrointestinal tract share certain features with inflammatory processes, suggesting that the release of inflammation cytokines such as TNF-alpha may damage the intestine. 2. Rats received a s.c. injection of indomethacin. Then, jejunum-ileum was taken up for the quantification of ulcerations, production of TNF-alpha, nitrites and PGE2 ex vivo and activity of calcium-independent NO synthase and myeloperoxydase. Activation of NO metabolism and myeloperoxydase were measured as potential effectors of TNF-alpha. 3. Jejunum-ileum from rats having received indomethacin (10 mg kg(-1)) produced TNF-alpha ex vivo. Cytokine production was associated with the onset of macroscopic ulcerations of the small intestine, and preceded nitrite production and tissue activity of myeloperoxidase. 4. Similar intestinal ulcerations and upregulation of TNF-alpha were obtained with flurbiprofen (30 mg kg(-1)), chemically unrelated to indomethacin. 5. TNF-alpha production was proportional to the indomethacin dose (from 3-20 mg kg(-1)) and correlated with the surface area of ulcerations and nitrite production, 24 h after indomethacin administration. 6. Pretreatment of rats with RO 20-1724, a type-IV phosphodiesterase inhibitor which inhibits TNF-alpha synthesis, substantially reduced jejunum-ileum ulcerations, TNF-alpha and nitrite production and tissue enzyme activities. 7. These findings provide evidence that TNF-alpha is increased in indomethacin-induced intestinal ulcerations and support suggestions that TNF-alpha is involved at an early stage of nonsteroidal anti-inflammatory drug toxicity for the small intestine.

Rats transgenic for HLA-B27 and human beta 2-microglobulin develop a spontaneous, multisystem, inflammatory disease that resembles human B27-associated disease and that involves the gut mucosa. This model predominantly affects the colon and is characterized by an extensive infiltration of the mucosa by inflammatory cells, largely composed of mononuclear cells. In addition, an increased plasma level of nitric oxide (NO)-derived metabolites was described in this model. Deficiency in the anti-inflammatory cytokine, interleukin-10 (IL-10), leads to the development of colitis in IL-10 knockout mice, suggesting that IL-10 plays a major role in the control of gut inflammation. The objectives of this work were to study the mechanisms of the inflammatory bowel disease (IBD) in HLA-B27 rats and to determine the effects of treatment with IL-10. The 33-3 line of HLA-B27 recombinant rats with established disease was treated in two consecutive experiments with murine recombinant IL-10 for five weeks. Assessment of the effect of this treatment was performed, based on clinical, histological and biological (myeloperoxidase and inducible NO synthase activities; tumor necrosis factor-alpha, interferon-delta, CD3, iNOS and beta-actin mRNA expression. In 33-3 rats with established disease, mesenteric lymph nodes were hyperplastic, and colonic cellularity and MPO and iNOS activities in the colonic mucosa were increased without any detectable effects of IL-10 administration. IFN-gamma and iNOS mRNA were only detected in the colon of transgenic rats. Despite a lack of effect on disease expression, IL-10 strikingly reduced the level of IFN-gamma mRNA in gut mucosa. Up-regulation of IFN-gamma mRNA suggests that the IBD of HLA-B27 rats is mediated by T-helper 1 lymphocytes. Sustained administration of IL-10, in HLA-B27 rats with established disease, efficiently inhibited IFN-gamma mRNA expression but did not influence disease expression: these results indicate that IFN-gamma may exert a critical role at an earlier stage of the disease rather in the maintenance of the lesions.

Cytogenetic anomalies described in colo-rectal tumors are numerous. Despite the complexity and the number of the anomalies observed, a combined study of their frequency and of the stage of prognosis of the tumors suggests that the evolution from colonic adenoma to carcinoma often follows a sequence of events comprising a 5q15-22 deletion (DCC), and a 17p deletion (P53). It even seems likely that in many cases, these events are not constant and that others might lead to the same phenotypic transformation. Chromosome 1 involvement in structural rearrangements has been demonstrated in numerous forms of cancers, malignant blood disorders and in solid tumors. In colorectal adenocarcinoma anomalies have been described on short and/or long arms. In a case of adenoma with mild dysplasia a deletion of the distal part of the short arm of chromosome 1 was observed as an isolated cytogenetic anomaly, suggesting it would be an early, perhaps triggering, event for the tumour development. A cytogenetic study in a series of colo-rectal tumours, researches on loss of heterozygosity and microsatellite instability lead to consider deletions at chromosome 1p as an early event in human colorectal tumourigenesis.

Patients with ulcerative colitis are at risk of low bone mineral density (BMD). Proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis diminishes the risk of bone disease. The aims of this study were to assess the mechanism of low BMD and to measure bone density changes after IPAA.Twenty patients with IPAA for ulcerative colitis, of mean(s.d.) age 38(9) (range 21-58) years, had measurements of lumbar spine and femoral neck BMD by dual energy X-ray absorptiometry, a mean(s.d.) 28(23) (range 3-84) months after proctocolectomy. Serum levels of calcium, phosphate, parathyroid hormone, osteocalcin and 25-hydroxy vitamin D were determined. Fifteen patients were followed for 28(12) (range 8-50) months.At baseline, six patients had spine BMD more than two standard deviations below the normal value, and three had vertebral crush fractures. Mean vitamin D values were normal and no patient had osteomalacia. BMD increased with time elapsed since IPAA (spine: r = 0.71, P = 0.005). During follow-up, mean(s.d.) changes in bone density were +2.3(3.8) and +2.1(5.6) per cent per year at the spine and femoral neck respectively.These results suggest that in patients with IPAA for ulcerative colitis, low BMD is not associated with vitamin D malabsorption and may be reversible after surgery.