bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of endoscopic biopsy surveillance of Barrett’s oesophagus on pathological stage and clinical outcome of Barrett’s carcinoma
Authors: van Sandick J W , van Lanschot J J B , Kuiken B W , Tytgat G N J , Offerhaus G J A , Obertop H 
Published: June 2010

Background—The efficacy of endoscopic biopsy surveillance of Barrett’s oesophagus in reducing mortality from oesophageal cancer has not been confirmed.Aims—To investigate the impact of endoscopic biopsy surveillance on pathological stage and clinical outcome of Barrett’s carcinoma.Methods—A clinicopathological comparison was made between patients who initially presented with oesophageal adenocarcinoma (n=54), and those in whom the cancer had been detected during surveillance of Barrett’s oesophagus (n=16).Results—The surveyed patients were known to have Barrett’s oesophagus for a median period of 42 months (range 6–144 months). Prior to the detection of adenocarcinoma or high grade dysplasia, 13 of 16 patients (81%) were previously found to have low grade dysplasia. Surgical pathology showed that surveyed patients had significantly earlier stages than non-surveyed patients (p=0.0001). Only one surveyed patient (6%) versus 34 non-surveyed patients (63%) had nodal involvement (p=0.0001). Two year survival was 85.9% for surveyed patients and 43.3% for non-surveyed patients (p=0.0029).Conclusions—The temporal course of histological progression in our surveyed patients supports the theory that adenocarcinoma in Barrett’s oesophagus develops through stages of increasing severity of dysplasia. Endoscopic biopsy surveillance of Barrett’s oesophagus permits detection of malignancy at an early and curable stage, thereby potentially reducing mortality from oesophageal adenocarcinoma.
Intraluminal capsaicin does not affect fluid and electrolyte absorption in the human jejunum but does cause pain
Authors: Hammer J , Hammer H F , Eherer A J , Petritsch W , Holzer P , Krejs G J 
Published: June 2010

Background—Stimulation of sensory nerves with capsaicin regulates ion transport in the small intestine in animal experiments.Aim—To investigate whether sensory nerves that are stimulated by capsaicin administration influence fluid and electrolyte absorption in the human jejunum in vivo.Method—Intestinal perfusion studies were performed in 12 healthy subjects using a four lumen tube with a proximal occlusion balloon and a plasma-like electrolyte solution. After an initial control period, 5 (n = 3), 10 (n = 8), or 50 (n = 1) μg/ml capsaicin was added to the perfusate, and this was followed by a final control period. Rates of absorption of water, sodium, potassium, chloride, and bicarbonate were determined in a 30 cm segment of jejunum using a non-absorbable volume marker.Results—At all three concentrations of capsaicin there were no significant changes in water and electrolyte absorption as compared with control periods. Two subjects who received 10 μg/ml and the subject receiving 50 μg/ml experienced crampy abdominal pain.Conclusion—The results do not support the hypothesis that capsaicin sensitive afferent nerves are involved in the physiological regulation of net absorption or secretion across the human jejunal mucosa. Chemical stimulation of these nerves, however, gives rise to abdominal pain.
HIV enteropathy: comparative morphometry of the jejunal mucosa of HIV infected patients resident in the United Kingdom and Uganda
Authors: Batman P A , Kapembwa M S , Miller A R O , Sedgwick P M , Lucas S , Sewankambo N K , Serwadda D , Pudney J , Moody A , Harris J R W , Griffin G E 
Published: June 2010

Aims—To compare jejunal mucosal morphometry in HIV infected patients resident in London and Uganda.Patients—Twenty HIV positive patients from London and 16 from Uganda were studied, and compared with HIV negative control subjects from both sites.Methods—Stools and biopsy specimens were examined for enteropathogens. Surface area to volume (S:V) ratio was estimated morphometrically, mean crypt length of jejunal biopsy specimens was measured, and HIV infected cells detected immunohistochemically were quantified.Results—Enteric pathogens were detected in none of the London patients, and in three Ugandan patients. S:V ratio was lower, and mean crypt length higher, in the specimens of London patients than in normal subjects, but there was no difference in S:V ratio or mean crypt length between Ugandan patients and controls. A negative correlation was present between S:V ratio and mean crypt length in all biopsy specimens analysed. HIV infected cells were detected only in lamina propria.Conclusion—Infection of cells in the lamina propria of the jejunum with HIV stimulates crypt cell proliferation, and a fall in villous surface area. The mucosal response to HIV is masked by other pathogens in the African environment.
Factors affecting splanchnic haemodynamics in Crohn’s disease: a prospective controlled study using Doppler ultrasound
Authors: Maconi G , Parente F , Bollani S , Imbesi V , Ardizzone S , Russo A , Porro G Bianchi 
Published: June 2010

Background—Current knowledge on splanchnic haemodynamics in Crohn’s disease is limited.Aims—To investigate which features of Crohn’s disease affect splanchnic haemodynamics, and to establish whether portal vein (PV) and superior mesenteric artery (SMA) blood supply reflects clinical or biochemical activity of Crohn’s disease.Methods—Seventy nine patients with Crohn’s disease and 40 controls were evaluated by Doppler ultrasound (US). The mean velocity of PV and SMA flow, the volume of blood flow of the PV and SMA, and the resistance index of SMA were studied. A series of clinical, biochemical, and US variables including Crohn’s disease activity index, serum C reactive protein concentrations, disease duration and its anatomical location, smoking habits, abdominal complications, and current medical therapy, as well as the maximum bowel wall thickness as measured by US, were determined. The relation between PV and SMA blood flow and these variables was assessed by univariate and multivariate analysis.Results—Patients with Crohn’s disease had significantly higher PV and SMA flow and a lower SMA resistance index than controls. Stepwise multiple regression analysis identified bowel wall thickness and location of the disease as the main predictive variables of both PV and SMA blood flow variation, accounting for 36% and 45% of their variability, respectively. No relation was found between splanchnic haemodynamics and disease activity.Conclusion—A hyperdynamic mesenteric circulation does exist in Crohn’s disease; however splanchnic blood flow does not reflect the clinical or biochemical activity of the disease, but seems to be linked more to other Crohn’s disease characteristics, such as maximum bowel thickness and anatomical location.
Are relatives of patients with multiple HNPCC spectrum tumours at increased risk of cancer?
Authors: Brown S R , Finan P J , Bishop D T 
Published: June 2010

Background—Relatives of patients with early onset colorectal cancer, a feature of hereditary non-polyposis colorectal cancer (HNPCC), are at increased risk of colorectal cancer.Aims—To investigate risk in relatives of patients with multiple primary cancers, another feature of HNPCC.Methods—Details were obtained on patients from one region who had developed colorectal cancer and a separate primary from the HNPCC tumour spectrum (colorectal, stomach, urinary, ovary, endometrial). Overall, 157 patients had second primaries occurring between 1990 and 1995 and 128 completed family histories were obtained by structured interview (study group). A comparison group of 444 patients with a single colorectal cancer were similarly interviewed.Results—Fifteen families (13%) from the study group were suggestive of HNPCC compared with three (0.7%, p<0.0001) from the comparison group. Overall risk of colorectal cancer in close relatives of the study group was 3.4 times the general population rate compared with 1.8 times for the comparison group. Bowel cancer risk was even higher for relatives of bowel/ovary and bowel/endometrial subgroups, but was similar to the comparison group for the bowel/bowel subgroup. Finally, extracolonic HNPCC associated cancers were seen twice as frequently as expected in the general population in relatives of the study group.Conclusion—This study highlights the importance of taking a family history in patients with multiple primary cancers and indicates the risk of malignancy in their relatives.
A UK training programme for nurse practitioner flexible sigmoidoscopy and a prospective evaluation of the practice of the first UK trained nurse flexible sigmoidoscopist
Authors: Duthie G S , Drew P J , Hughes M A P , Farouk R , Hodson R , Wedgwood K R , Monson J R T 
Published: June 2010

Background—Flexible sigmoidoscopy is a technical skill that has been successfully performed by suitably trained colorectal nurse practitioners in the USA. However, no recognised training course exists for nurse practitioners in the UK.Aims—To design and evaluate a training programme for nurse endoscopists.Methods—A multidisciplinary committee of nurses and clinicians developed a structured programme of study and practice. This involved a staged process of observations, withdrawals, and ultimately, full procedures. Once training had been completed the nurse practitioner was permitted to practice independently. Patients with colorectal symptoms referred for flexible sigmoidoscopy were examined for the final stages of training and independent practice. A prospective evaluation of the training and practice of the first trained nurse flexible sigmoidoscopist was performed. Barium enema, video, clinical follow up, and histology were used to validate the results of the flexible sigmoidoscopies.Results—The training programme required that 35 observations, 35 withdrawals, and 35 supervised full procedures were performed prior to the development of independent practice. Subsequent to the completion of this programme 215 patients have been examined independently by the nurse practitioner. Ninety three per cent of the examinations were judged successful and pathology was identified in 51%. The nurse endoscopist successfully identified all “significant” pathology whereas barium enema failed to identify pathology in 12.5%. There were no complications.Conclusion—With suitable training nurse endosocopists are able to perform flexible sigmoidoscopy safely and effectively.
5-Aminosalicylic acid prevents oxidant mediated damage of glyceraldehyde-3-phosphate dehydrogenase in colon epithelial cells
Authors: McKenzie S M , Doe W F , Buffinton G D 
Published: June 2010

BackgroundReactive oxygen and nitrogen derived species produced by activated neutrophils have been implicated in the damage of mucosal proteins including the inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the active inflammatory lesion in patients with inflammatory bowel disease (IBD). This study investigated the efficacy of currently used IBD therapeutics to prevent injury mediated by reactive oxygen and nitrogen derived species.MethodsGAPDH activity of human colon epithelial cells was used as a sensitive indicator of injury produced by reactive oxygen and nitrogen derived species. HCT116 cells (106/ml phosphate buffered saline; 37°C) were incubated in the presence of 5-aminosalicylic acid (5-ASA), 6-mercaptopurine, methylprednisolone, or metronidazole before exposure to H2O2, HOCl, or NO in vitro. HCT116 cell GAPDH enzyme activity was determined by standard procedures. Cell free reactions between 5-ASA and HOCl were analysed by spectrophotometry and fluorimetry to characterise the mechanism of oxidant scavenging.ResultsGAPDH activity of HCT116 cells was inhibited by the oxidants tested: the concentration that produced 50% inhibition (IC50) was 44.5 (2.1) μM for HOCl, 379.8 (21.3) μM for H2O2, and 685.8 (103.8) μM for NO (means (SEM)). 5-ASA was the only therapeutic compound tested to show efficacy (p<0.05) against HOCl mediated inhibition of enzyme activity; however, it was ineffective against H2O2 and NO mediated inhibition of GAPDH. Methylprednisolone, metronidazole, and the thiol-containing 6-mercaptopurine were ineffective against all oxidants. Studies at ratios of HOCl:5-ASA achievable in the mucosa showed direct scavenging to be the mechanism of protection of GAPDH activity. Mixing 5-ASA and HOCl before addition to the cells resulted in significantly greater protection of GAPDH activity than when HOCl was added to cells preincubated with 5-ASA. The addition of 5-ASA after HOCl exposure did not restore GAPDH activity.ConclusionsTherapies based on 5-ASA may play a direct role in scavenging the potent neutrophil oxidant HOCl, thereby protecting mucosal GAPDH from oxidative inhibition. These findings suggest that strategies for the further development of new HOCl scavenging compounds may be useful in the treatment of IBD.
Macromolecular transport across the rabbit proximal and distal colon
Authors: Hardin J A , Kimm M H , Wirasinghe M , Gall D G 
Published: June 2010

BackgroundAlthough many studies have investigated macromolecular uptake in the stomach and small intestine, little is known about macromolecular uptake in the colon.AimsTo investigate the mechanisms involved in the transport of large antigenically intact macromolecules across the proximal and distal colonic epithelium in the rabbit.MethodsThe mucosal to serosal movement of bovine serum albumin (BSA) was examined in modified Ussing chambers under short circuited conditions. The mucosal surface was exposed to varying concentrations of BSA, and after a 50 minute equilibration period, the mucosal to serosal flux of immunologically intact BSA was determined by ELISA. Total BSA flux was determined by the transport of radiolabelled 125I-BSA.ResultsIntact BSA transport in proximal and distal colonic tissue showed saturable kinetics. Intact BSA transport in the proximal and distal segment was 7% and 2% of the total 125I-BSA flux respectively. Immunologically intact BSA transport in the distal segment was significantly less than that in the proximal segment. Intact BSA transport in the proximal colon was significantly reduced following treatment with sodium fluoride, colchicine, and tetrodotoxin. Cholinergic blockade had no effect on the uptake of intact BSA.ConclusionThe findings indicate that the transport of intact macromolecules across the proximal and distal large intestine is a saturable process. Further, intact BSA transport in the proximal colon is an energy dependent process that utilises microtubules and is regulated by the enteric nervous system.
A blind comparison of the effectiveness of endoscopic ultrasonography and endoscopy in staging early gastric cancer
Authors: Yanai H , Noguchi T , Mizumachi S , Tokiyama H , Nakamura H , Tada M , Okita K 
Published: June 2010

BACKGROUND/AIMSEndoscopic ultrasonography is expected to be useful for invasion depth staging of early gastric cancer. A prospective blind study of the staging characteristics of endoscopy and endoscopic ultrasonography for early gastric cancer was performed.METHODSFindings of endoscopy and endoscopic ultrasonography using a 20 MHz thin ultrasound probe were independently reviewed and the results of 52 early gastric cancer lesions analysed.RESULTSThe overall accuracy rates in invasion depth staging of early gastric cancer were 63% for endoscopy and 71% for endoscopic ultrasonography. No statistically significant differences were observed in overall accuracy. Endoscopic ultrasonography tended to overstage, and lesions that were classified as mucosal cancer by endoscopic ultrasonography were very likely (95%) to be limited to the mucosa on histological examination. All 16 lesions staged as mucosal cancer independently but coincidentally by both methods were histologically limited to the mucosa.CONCLUSIONSEndoscopic ultrasonography is expected to compensate for the understaging of lesions with submucosal invasion that are endoscopically staged as mucosal cancer.
Vicia faba agglutinin, the lectin present in broad beans, stimulates differentiation of undifferentiated colon cancer cells
Authors: Jordinson M , El-Hariry I , Calnan D , Calam J , Pignatelli M 
Published: June 2010

BACKGROUNDDietary lectins can alter the proliferation of colonic cells. Differentiation is regulated by adhesion molecules which, being glycosylated, are targets for lectin binding.AIMSTo examine the effects of dietary lectins on differentiation, adhesion, and proliferation of colorectal cancer cells. METHODSDifferentiation was assessed in three dimensional gels, adhesion by aggregation assay, and proliferation by 3H thymidine incorporation. The role of the epithelial cell adhesion molecule (epCAM) was studied using a specific monoclonal antibody in blocking studies and Western blots. The human colon cancer cell lines LS174T, SW1222, and HT29 were studied.RESULTSThe cell line LS174T differentiated in the presence of Vicia fabaagglutinin (VFA) into gland like structures. This was inhibited by anti-epCAM monoclonal antibody. Expression of epCAM itself was unaffected. VFA as well as wheat germ agglutinin (WGA) and the edible mushroom lectin (Agaricus bisporus lectin, ABL) significantly aggregated LS174T cells but peanut agglutinin (PNA) and soybean agglutinin (SBA) did not. All lectins aggregated SW1222 and HT29 cells. Aggregation was blocked by the corresponding sugars. Aggregation of cells by VFA was also inhibited by anti-epCAM. VFA, ABL, and WGL inhibited proliferation of all the cell lines; PNA stimulated proliferation of HT29 and SW1222 cells. In competition studies all sugars blocked aggregation and proliferation of all cell lines, except that the addition of mannose alone inhibited proliferation.CONCLUSIONVFA stimulated an undifferentiated colon cancer cell line to differentiate into gland like structures. The adhesion molecule epCAM is involved in this. Dietary or therapeutic VFA may slow progression of colon cancer.
Genetic epidemiology of mutated K-rasproto-oncogene, altered suppressor genes, and microsatellite instability in colorectal adenomas
Authors: Rashid A , Zahurak M , Goodman S N , Hamilton S R 
Published: June 2010

BACKGROUNDThe genetic epidemiology of colorectal adenomas has not been studied prospectively in colonoscopy patients without cancer.AIMSTo study genetic alterations in colorectal adenomas and correlate these with patient demographics and adenoma characteristics.METHODSMutations and allelic deletions in 201 adenomas from 60 patients were compared with demographic features, adenoma characteristics, and family history.RESULTSThe most common alteration was K-ras proto-oncogene mutation, present in 35% of adenomas and 65% of patients. Patients 65 years of age and older had a decreased probability of K-ras mutations (26% versus 45%). Overexpression of p53 gene product was present in only 6% of adenomas but was more frequent in villous or tubulovillous adenomas (19% versus 3%). Allelic loss of chromosome 18q was present in only 2% of adenomas and was significantly less frequent than p53 overexpression. DNA replication errors (RER) were present in 7% of adenomas and 15% of patients, including multiple adenomas in four patients (two with hereditary non-polyposis colorectal cancer syndrome). Only 36% of RER positive adenomas had alteration of BAT-26 alleles, none had alteration of BAT-25, and only one (8%) had mutation in the transforming growth factor β type II receptor gene. RER positive adenomas were more likely to have a K-ras mutation. In patients with multiple adenomas, there was concordance of p53 overexpression and RER but not of K-ras mutations.CONCLUSIONSGenetic progression in colorectal adenomas is heterogeneous, involving factors related to patient age and the presence of RER for the occurrence of ras mutations, but different intraindividual characteristics for the occurrence of p53 alterations and RER.
High mobility group (HMG) non-histone chromosomal proteins HMG1 and HMG2 are significant target antigens of perinuclear anti-neutrophil cytoplasmic antibodies in autoimmune hepatitis
Authors: Sobajima J , Ozaki S , Uesugi H , Osakada F , Inoue M , Fukuda Y , Shirakawa H , Yoshida M , Rokuhara A , Imai H , Kiyosawa K , Nakao K 
Published: June 2010

BACKGROUNDHigh mobility group (HMG) non-histone chromosomal proteins HMG1 and HMG2 have been identified as novel antigens of perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCAs), and the existence of anti-HMG1 and anti-HMG2 antibodies in a population of patients with ulcerative colitis has been reported.AIMSTo investigate whether HMG1 and HMG2 are target antigens for p-ANCAs in autoimmune hepatitis (AIH).PATIENTSSerum samples from 28 patients with AIH, 44 patients with primary biliary cirrhosis (PBC), 27 patients with chronic hepatitis C, and 23 patients with chronic hepatitis B were tested.METHODSANCAs were detected by routine indirect immunofluorescence (IIF). Anti-HMG1 and anti-HMG2 antibodies were assayed by enzyme linked immunosorbent assay.RESULTSp-ANCAs were detected in 89% (25/28) of patients with AIH, 36% (16/44) of patients with PBC, 11% (3/27) of patients with chronic hepatitis C, and 13% (3/23) of patients with chronic hepatitis B. Anti-HMG1 and/or anti-HMG2 antibodies were detected in 89% (25/28) of patients with AIH, 70% (31/44) with PBC, 26% (7/27) with chronic hepatitis C, and 9% (2/23) with chronic hepatitis B. In AIH, anti-HMG1 and/or anti-HMG2 antibodies were detected in 96% (24/25) of p-ANCA positive patients. The p-ANCA staining pattern detected by IIF using sera from patients with AIH disappeared or decreased in titre after preincubation with a mixture of HMG1/HMG2. The presence and titres of those antibodies in AIH correlated significantly with those of p-ANCA, but not with those of anti-nuclear antibody or anti-smooth muscle antibody.CONCLUSIONSHMG1 and HMG2 are significant target antigens of p-ANCA in AIH.
Application of a novel and low cost technique to construct paraffin tissue microarrays out of paraffinised needle biopsy specimens from patients with breast cancer
Authors: Vogel Ulrich Felix , Bültmann Burkhard 
Published: June 2010

BackgroundParaffin tissue microarrays (TMAs) are a well accepted tool in pathology for high throughput molecular profiling, quality control and clinicopathological trials. No reports on TMAs constructed from paraffinised needle biopsy specimens (PNBSs) derived from patients with breast cancer can be found in the literature. PNBSs are sometimes the only source for tumour characterisation important for treatment.AimTo develop a novel and low cost technique to construct TMAs from PNBSs (PNBSs–TMAs) in order to close this gap in TMA technology.MethodsUsing a skin biopsy punch, tumour-bearing parts of 84 PNBSs were punched out of the donor blocks, freed from the surrounding paraffin by melting and manually transferred into the preformed holes in the recipient block. After filling the holes, the PNBSs–TMA was fixed to a double sided adhesive tape and completely melted. Quality assessment of this new technique was performed comparing the HER2 status (synonym: cerbB2) of the PNBSs–TMA with the results of the original PNBSs and a TMA harbouring the tumour in corresponding resection and mastectomy specimens (RM–TMA).ResultsA 187-hole PNBSs–TMA with 84 PNBSs was successfully constructed. About 1% of the included PNBSs displayed signs of rolling and folding or of floating off the slide during the staining procedure. The results of immunohistochemistry, fluorescence in situ hybridisation and automated brightfield double in situ hybridisation showed high quality standard of the PNBSs–TMA, suitable for precise tumour profiling.ConclusionsPNBSs–TMAs are suitable for clinicopathological trials, especially those in which PNBSs are the only tumour source.