bluuebunny/crossref_metadata_2025_split huggingface dataset:
The natural history of histologically proved drug induced liver disease
Authors: Aithal P G , Day C P 
Published: June 2010

BACKGROUNDThe long term outcome of drug related liver disease is unknown.AIMSTo study the natural history of histologically proved drug induced hepatotoxicity.METHODS110 patients with liver biopsies coded either as drug induced liver disease or hepatitis/cholestasis of unknown aetiology were identified from hospital records 1978–1996. Review of case notes and histology identified 44 patients with definite drug induced hepatotoxicity. Forty surviving patients were invited to attend a follow up clinic. History, examination, full liver screen, and isotope and ultrasound liver scans were repeated in all patients. Repeat liver biopsies were offered to patients with abnormal liver tests.RESULTSPresentation at index biopsy was jaundice in 24 patients, abnormal liver tests in 17, and hepatic failure in three. Antibiotics (n=13) and non-steroidal anti-inflammatory drugs (n=11) were the most common drugs implicated. Initial histology showed acute hepatitis in six, chronic hepatitis in 20, and cholestasis in 18. At 1–19 years (median 5 years) follow up, 13/33 (39%) patients had persistent significant abnormalities in their liver blood tests and/or scans. Three of the five repeat liver biopsies performed showed significant abnormalities. Factors predicting persistence or development of chronic liver disease were fibrosis and continued exposure to the drug.CONCLUSIONSDrugs should be considered in the differential diagnosis of abnormal liver function and/or histology, as failure to withdraw the offending drug is associated with a high risk of persistent liver damage.
Molecular screening of patients with long standing extensive ulcerative colitis: detection of p53 and Ki-ras mutations by single strand conformation polymorphism analysis and differential hybridisation in colonic lavage fluid
Authors: Lang S M , Stratakis D F , Heinzlmann M , Heldwein W , Wiebecke B , Loeschke K 
Published: June 2010

BACKGROUNDIn patients with long standing ulcerative colitis at risk of developing malignancy, mutations of the p53 and Ki-ras gene were investigated in lavage solution obtained at surveillance colonoscopy.METHODSDNA was isolated from 31 consecutive patients with total or subtotal ulcerative colitis and a disease duration of between seven and 26 years. Twenty seven control patients showed no macroscopic or microscopic inflammation on colonoscopy. Exons 5–8 of the p53 gene and exon 1 of the Ki-ras gene were amplified by polymerase chain reaction. Mutations of the p53 gene were detected by single strand conformation polymorphism analysis. Point mutations of the Ki-ras gene were hybridised on dot blots with oligonucleotides marked with digoxigenin.RESULTSIn all cases of ulcerative colitis and in all of the 27 control patients, wild type p53 and wild type Ki-ras could be detected. In four patients with ulcerative colitis, a mutation in exon 5 to 7 of the p53 gene was found, and two patients had a mutation of the Ki-ras gene (Gly to Asp-12, Gly to Val-12). None of these patients had dysplasia in serial biopsy specimens, and all but one had had the disease for more than 10 years. One control patient had a mutation.CONCLUSIONSMutations were more frequent in patients with long standing ulcerative colitis (19%) than in control patients (3%, p = 0.07). The technique may be useful for screening for early malignancy in ulcerative colitis.
Clinical course and risk factors of hepatitis C virus related liver disease in the general population: report from the Dionysos study
Authors: Bellentani S , Pozzato G , Saccoccio G , Crovatto M , Crocè L S , Mazzoran L , Masutti F , Cristianini G , Tiribelli C 
Published: June 2010

BACKGROUNDThe severity, clinical course, and risk of hepatitis C virus (HCV) related chronic liver disease are still rather poorly defined.AIMSTo investigate the prevalence, risk factors, and severity of HCV related liver disease in the general population, and investigate whether infection with a specific genotype is associated with an increased risk of cirrhosis or hepatocellular carcinoma.METHODSHCV RNA determination by polymerase chain reaction (PCR) and HCV genotyping were performed in all anti-HCV positive subjects belonging to the Dionysos study (6917 subjects). Diagnosis of cirrhosis and hepatocellular carcinoma was established by liver biopsy in all cases. All the data were analysed by univariate and multivariate statistics in all the cohort. To investigate the natural history of HCV infection, anti-HCV positive subjects were followed up every six months for three years with liver function tests and ultrasonograms.RESULTSThe overall prevalence of HCV RNA positivity was 2.3%. Positivity increased progressively with age, and was higher in women (ratio of men to women = 0.7). Genotypes 1b and 2a were the most frequent (42 and 24% of HCV RNA positive patients), with a prevalence of 1 and 0.6% respectively. Intravenous drug use, blood transfusions received before 1990, history of previous hepatitis among the cohabiting, and history of animal (mainly dogs) bites were significantly (p<0.05) associated with HCV infection, independently of age and sex. Multivariate analysis showed that, independently of age, sex, and alcohol intake, genotype 1b infection, with or without coinfection with other genotypes, is the major risk factor associated with the presence of cirrhosis and/or hepatocellular carcinoma. During the three years of follow up, 57 (35%) of the HCV RNA positive subjects had consistently normal alanine aminotransferase and γ-glutamyltransferase values. Two of the 22 HCV RNA positive cirrhotic patients, all drinking more than 90 g of alcohol a day, developed hepatocellular carcinoma (incidence rate = 3.0% per year).CONCLUSIONSIn the general population of Northern Italy, HCV infection is widespread, but only less than 50% of the anti-HCV positive subjects, particularly those infected with genotype 1b, are associated with a more severe liver disease. Alcohol consumption greater that 30 g a day significantly aggravates the natural course of the disease.
Predicting therapeutic outcome in severe ulcerative colitis by measuring in vitro steroid sensitivity of proliferating peripheral blood lymphocytes
Authors: Hearing S D , Norman M , Probert C S J , Haslam N , Dayan C M 
Published: June 2010

BACKGROUNDUp to 29% of patients with severe ulcerative colitis (UC) fail to respond to steroid treatment and require surgery. Previous studies have failed to show a clear correlation between failure of steroid treatment in severe UC and measures of disease severity. The reasons for treatment failure therefore remain unknown.AIMTo investigate the hypothesis that patients with severe UC who fail to respond to steroid treatment have steroid resistant T lymphocytes.METHODSEighteen patients with severe UC were studied. After seven days’ treatment with high dose intravenous steroids they were classified as complete responders (CR), incomplete responders (IR), or treatment failures (TF). Within 48 hours of admission blood was taken and the antiproliferative effect of dexamethasone on phytohaemagglutinin stimulated peripheral blood T lymphocytes was measured. Maximum dexamethasone induced inhibition of proliferation (Imax) was measured.RESULTSIn vitro T lymphocyte steroid sensitivity of TF and IR patients was significantly less than that of CR patients. Both TF and 3/5 IR patients had an Imax of less than 60%; all CR patients had an Imax of greater than 60%. No significant correlation was seen between response to treatment and disease severity on admission. When in vitro T lymphocyte steroid sensitivity was remeasured three months later, there was no difference between the groups.CONCLUSIONSResults suggest that T lymphocyte steroid resistance is an important factor in determining response to steroid treatment in patients with severe UC and may be more predictive of outcome than disease severity.
Increased prevalence of methylenetetrahydrofolate reductase C677T variant in patients with inflammatory bowel disease, and its clinical implications
Authors: Mahmud N , Molloy A , McPartlin J , Corbally R , Whitehead A S , Scott J M , Weir D G 
Published: June 2010

BACKGROUNDInflammatory bowel disease (IBD) is associated with an increased incidence of thromboembolic disease. Hyperhomocysteinaemia (hyper-tHcy), a condition associated with the C677T variant of 5,10-methylenetetrahydrofolate reductase (MTHFR), is linked with an increased incidence of thromboembolic disease. Hyper-tHcy has been reported in patients with IBD.AIMSTo assess the prevalence of the C677T MTHFR genotype and the contribution of this genotype to hyper-tHcy in patients with IBD.METHODSPatients with established IBD (n=174) and healthy controls (n=273) were studied. DNA samples were genotyped for the MTHFR (C677T) mutation. Subjects were categorised as homozygous for the thermolabile variant (TT), heterozygous for wild type and variant (CT), or homozygous for the wild type (CC).RESULTSPlasma homocysteine concentrations were significantly higher in patients with IBD than in healthy controls. A total of 17.5% of ulcerative colitis and 16.8% of Crohn’s disease patients were homozygous for the C677T variant compared with 7.3% of controls. Homozygosity (TT) for the variant was associated with higher plasma tHcy levels in patients with IBD and in healthy controls. When all subjects who were TT for the variant were excluded, median plasma tHcy was still significantly higher in IBD than controls. Plasma vitamin B12 levels were lower in patients with IBD irrespective of MTHFR genotype.CONCLUSIONSThere is an association between the thermolabile MTHFR C677T variant and IBD. This accounts in part for the raised plasma tHcy found in patients with IBD and may contribute to the increased incidence of thromboembolic complications. All patients with IBD should receive low dose folic acid and vitamin B12 therapy to protect against the thromboembolic complications of raised tHcy.
Choice of management strategy for colorectal cancer based on a diagnostic immunohistochemical test for defective mismatch repair
Authors: Cawkwell L , Gray S , Murgatroyd H , Sutherland F , Haine L , Longfellow M , O’Loughlin S , Cross D , Kronborg O , Fenger C , Mapstone N , Dixon M , Quirke P 
Published: June 2010

BACKGROUNDDespite intensive research into the molecular abnormalities associated with colorectal cancer (CRC), no diagnostic tests have emerged which usefully complement standard histopathological assessments.AIMSTo assess the feasibility of using immunohistochemistry to detect replication error (RER) positive CRCs and determine the incidence of RER positivity within distinct patient subgroups.METHODS502 CRCs were analysed for RER positivity (at least two markers affected) and/or expression of hMSH2 and hMLH1.RESULTSThere were 15/30 (50%) patients with metachronous CRCs, 16/51 (31%) with synchronous CRCs, 14/45 (31%) with a proximal colon carcinoma, and 4/23 (17%) who developed a CRC under the age of 50 showed RER positivity. However, 0/54 patients who developed a solitary carcinoma of the rectum/left colon over the age of 50 showed RER positivity. Immunohistochemical analysis revealed that 66/66 (100%) RER positive carcinomas were associated with complete lack of expression of either hMSH2 or hMLH1. This correlation was confirmed using a further 101 proximal colon carcinomas. Patients with a mismatch repair defective carcinoma showed improved survival but a 5.54 times relative risk of developing a metachronous CRC. A prospective immunohistochemical study revealed 13/117 (11%) patients had a mismatch repair defective carcinoma. A fivefold excess of hMLH1 defective cases was noted.CONCLUSIONSAll RER positive carcinomas were identified by the immunohistochemical test. This is the first simple laboratory test which can be performed routinely on all CRCs. It will provide a method for selecting patients who should be investigated for HNPCC, offered long term follow up, and who may not respond to standard chemotherapy regimens.
Hepatic manifestations of familial patent ductus venosus in adults
Authors: Jacob S , Farr G , De Vun D , Takiff H , Mason A 
Published: June 2010

BACKGROUNDThe ductus venosus connects the umbilical vein to the inferior vena cava during fetal life and subsequently closes rapidly after birth. It is known as patent ductus venosus when it remains patent in adulthood.PATIENTSA 43 year old man with a history of panhypopituitarism presented with recurrent bouts of pedal oedema associated with fatigue, hypoalbuminaemia, and elevated prothrombin time. An ultrasound examination of his abdomen with Doppler revealed notable attenuation of the main portal vein with diminished intrahepatic branches; a computed tomography scan with angiography revealed a large collateral vein within the liver consistent with a patent ductus venosus. Sequential liver biopsies showed a considerable reduction in the calibre and number of the portal veins. His younger brother, who was diagnosed with alcohol related cirrhosis, suffered from intermittent bouts of encephalopathy and was found to have the same vascular lesion. A third brother was found to have a patent ductus venosus as well as two large hepatic masses consistent with focal nodular hyperplasia.CONCLUSIONThe syndrome of familial patent ductus venosus has only previously been described in three infant brothers who presented with hepatic encephalopathy and fatty degeneration of the liver. This report documents three brothers with a patent ductus venosus presenting in adulthood with different manifestations of liver disease. The presence of the same vascular anomaly in three brothers is highly suggestive of a recessive genetic trait with an anatomical manifestation of patent ductus venosus.
The effects of short term lipid infusion on plasma and hepatic bile lipids in humans
Authors: Pakula R , Konikoff F M , Moser A M , Greif F , Tietz A , Gilat T , Rubin M 
Published: June 2010

BACKGROUNDPatients on parenteral nutrition have an increased incidence of gall bladder sludge and gallstone disease, thought to be related to bile stasis. Intravenous lipid emulsions, especially those containing medium chain triglycerides, have also been shown to have a lithogenic effect on the composition of bile in the gall bladder.AIMSTo determine whether lipid infusion influences hepatic bile composition in patients with an indwelling T tube following cholecystectomy and choledochotomy.METHODSIn eight patients undergoing the above surgical procedure, the time at which effects of the interrupted enterohepatic circulation were minimal was determined. Twenty two cholesterol gallstone patients with bile fistula were then randomised to receive an infusion of a lipid emulsion containing either long chain triglycerides or a mixture of long and medium chain triglycerides.RESULTSLipid infusion resulted in a significant increase in plasma levels of triglycerides and phospholipids. Both lipid emulsions caused an increase in hepatic biliary cholesterol level and cholesterol saturation index, but this effect was more pronounced with medium chain triglycerides. The fatty acid composition of biliary phospholipids showed a significant enrichment of linoleic acid by both lipid infusions.CONCLUSIONSInfusion of triglycerides causes lithogenic changes in hepatic bile composition in humans, the lithogenic effect of infusion of medium chain triglycerides being more pronounced than that of long chain triglycerides. This effect, coupled with gall bladder stasis, may be responsible for the increased risk of biliary sludge and gallstone formation in patients on long term lipid infusion.
Firearms regulation and declining rates of male suicide in Quebec
Authors: Gagné Mathieu , Robitaille Yvonne , Hamel Denis , St-Laurent Danielle 
Published: June 2010

ObjectivesTo examine whether significant changes in method-specific male suicide rates occurred in the province of Quebec after stronger firearms regulations were introduced in Canada in 1991; to ascertain whether more stringent firearms regulations influence firearms and total suicide trends among men and to determine whether different results are obtained according to the statistical methods used.Study designDescriptive analyses of time trends in method-specific suicide rates for men from 1981 to 2006 using Joinpoint regression models and pre–post firearms regulation analyses.SettingQuebec (Canada).Patients or SubjectsMen who have commited suicide aged 15–34, 35–64 and 65 years and over, based on the Quebec mortality database, 1981–2006.InterventionsA national firearms control initiative enacted in 1991.ResultsThe Joinpoint regression models suggest that firearm suicide rates declined towards the end of the 1990s. Since 1996, the pace of decline was twice as great in men aged 15–34 years (annual percentage change (APC) −11.1%) compared with men aged 35–64 years (APC −5.6%). Total suicide rates also declined among men aged 15–34 and 35–64 years during this period. Pre–post firearms regulation Poisson regression analyses failed to detect the specific point in time when significant changes in the trend occurred.ConclusionsMale firearm suicide rates declined following the introduction of restrictive firearms regulations in Canada. Whether this represents a causal relationship requires further study.
Is length of stay in hospital a stable proxy for injury severity?
Authors: Cryer C , Gulliver P , Langley J D , Davie G 
Published: June 2010

Research questionIs length of stay (LoS) in hospital a stable proxy for severity of injury when monitoring time trends in serious injury incidence?ObjectiveTo investigate whether LoS metrics (mean, median and proportion exceeding several LoS thresholds) have changed over time for injury diagnoses with known severity.DesignTime series investigation.Subjects and settingNew Zealand population admitted to hospital for injury and discharged during the period 1989 to 1998.Main outcome measuresInterpolated median and geometric mean lengths of stay, as well as the proportion of cases that have an LoS greater than or equal to 3, 4, 7 and 14 days in hospital.MethodsICD-9-CM diagnoses that are approximately homogeneous in regard to severity of injury (ICD-HS diagnoses) were identified. Trends were investigated in the LoS statistics for: injury and non-injury diagnoses combined; all injury diagnoses; major body sites of injury; severity strata; and ICD-HS diagnoses.ResultsAlmost without exception, there was a decline in the LoS statistics over time for all diagnoses, all injury diagnoses, each body site of injury investigated, severity strata, and the ICD-HS diagnoses.ConclusionsReductions in median and geometric mean LoS over time, as well as reductions in the proportion exceeding selected LoS thresholds, were due to factors other than reductions in the incidence of serious injury; for example, changes in service delivery over time. An LoS threshold shouldnotbe used as a proxy for severity of injury if the goal is to monitor time trends in injury incidence.
Oral squamous cell carcinoma: status of tight junction claudins in the different histopathological patterns and relationship with clinical parameters. A tissue-microarray-based study of 136 cases
Authors: Lourenço Silvia V , Coutinho-Camillo Cláudia M , Buim Marcilei E C , Pereira Cláudia M , Carvalho André L , Kowalski Luiz P , Soares Fernando A 
Published: June 2010

AimsClaudins are integral transmembrane proteins of the tight junctions, critical for maintaining cell adhesion and polarity. Alterations in the expression of individual claudins have been detected in carcinomas and appear to correlate with tumour progression.MethodsIn this study, a panel of anti-claudin antibodies (anti-claudins 1, 2, 3, 4, 5 and 7) was employed to map claudin expression in 136 cases of oral squamous cell carcinoma (OSCC) organised in a tissue microarray.ResultsClaudins were expressed in a reticular pattern up to the prickle layer in normal mucosal epithelium. In OSCC, claudins were strongly present in well-differentiated tumours, they presented mild and low expression in moderately differentiated OSCC, and were negative in poorly differentiated OSCC; the absences of claudin 1 (p=0.002) and claudin 4 (p<0.001) were associated with moderately/poorly differentiated tumours. Strong expression of claudin 4 was associated with decreased perineural infiltration (p=0.024). Claudins 5 and 7 were mostly negative or weakly expressed in all cases studied. Expression of claudin 7 was associated with the early clinical stages of the disease, whereas loss of claudin 7 tended to be more frequent in advanced stages of OSCC (p=0.054). Absence of claudin 7 was also associated with absent vascular infiltration (p=0.045) and with presence of recurrence (p=0.052).ConclusionsClaudin expression patterns showed a strong correlation with histological type of OSCC; claudin expression was decreased in areas of invasion, and negative in poorly differentiated tumours. This pattern may be related to evolution and prognosis of these tumours, especially in the case of claudin 7, which seems to be associated with a poor prognosis in OSCC.
E-cadherin immunoexpression patterns in the characterisation of gastric carcinoma histotypes
Authors: Almeida P R , Ferreira V A , Santos C C , Rocha-Filho F D , Feitosa R R , Falcão E A A , Cavada B K , Ribeiro R A 
Published: June 2010

AimsE-cadherin, the main epithelial intercellular adhesion molecule, is abnormally expressed in many cancer types, including gastric carcinoma, which is the second leading cause of cancer death worldwide. The aim of this study was to contribute to the characterisation of gastric carcinoma histotypes based on a new approach to E-cadherin immunoexpression.Methods97 gastric tumour samples obtained from the files of the Hospital of Cancer/Cancer Institute of Ceará, Brazil, were histologically analysed and classified as intestinal (n=40), diffuse (n=34), mixed (n=16) or unclassified (n=7) carcinomas. Immunohistochemistry was performed on the tissue microarray sections. Scores were applied according to the system of Jawhari: 0, no staining; 1, cytoplasmic staining; 2, cytoplasmic and membranous staining in the same case; 3, normal membranous immunoexpression; abnormal patterns: scores 0, 1 and 2; normal pattern: score 3. Jawhari scores were then evaluated utilising another approach: the absence of membranous expression scores (0 and 1) versus the presence of membranous expression (scores 2 and 3).ResultsA significant association between membranous expression of E-cadherin and the intestinal histotype (36/40 (90%), and 28/41 (68%) for other histotypes) was found, while diffuse carcinomas were related to the absence of membranous expression. A very strong and peculiar relationship was observed between cytoplasm-exclusive E-cadherin expression (score 1) and the diffuse component of mixed tumours (11/16 (69%)).ConclusionsE-cadherin immunoexpression patterns help us to characterise gastric carcinoma histotypes. The presence or absence of membranous staining is the most valuable criterion in evaluating E-cadherin expression. Mixed tumours show a characteristic E-cadherin cytoplasmic expression in gastric carcinomas.