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AbstractZebra mussels ( Dreissena polymorpha ), first reported in Texas during 2009, have infested 28 Texas reservoirs over 11 years. This species has not previously invaded water bodies as warm as those in Texas, where temperatures approach or exceed its previously accepted incipient upper thermal limit of 30 °C, raising the question of how such temperatures impact its population dynamics. Over 3-5 years, monthly collections of mussels, sampling for planktonic mussel veligers, juvenile settlement data, and water quality parameters, were undertaken at Texas lakes Texoma, Ray Roberts, and Belton to estimate mussel shell length growth rates, life spans, reproductive periods, and settlement patterns. Biannual spawning periods occurred at water temperatures of 18 to 28 °C, resulting in distinct spring and fall juvenile settlement cohorts. Growth rates were rapid, with both cohorts attaining mean maximum shell lengths of 20-25 mm within 8-15 months of settlement, compared to European and northeastern US populations that attained similar sizes after 2-4 years. Shortened life spans were demarcated by adult mussel die-offs during summer months of elevated water temperature the year after initial settlement, leading to short-term cyclical fluctuations in population densities. Large-scale mussel die-offs were caused by flooding and hypoxia events. Elevated temperatures appeared to facilitate mussel invasiveness by increasing spawning frequency and elevating growth rates, thus reducing time to maturity and allowing population recovery within 1-2 years after environmentally induced severe population declines.

Objectives: The histopathological mechanisms underlying portal hypertension in primary biliary cholangitis (PBC) are poorly understood, as is its natural history. We have therefore determined the prevalence, severity and progression of portal hypertension in PBC and investigated whether its presence is related to specific histological lesions., Methods: Hepatic venous pressure gradient (HVPG) was measured in 86 patients, with 186 assessments over up to 7 years of follow-up and the results correlated with a semiquantitative grading of 8 histological features and nodular regenerative hyperplasia (NRH)., Results: Portal hypertension (HVPG >5 mmHg) was present in 88% of all assessments (86% at baseline), and in 45% of patients at baseline was >12 mmHg (high-risk portal hypertension). The rise in portal pressure occurs early in the disease, since 45% of patients with normal serum bilirubin had a raised HVPG, as did 72% of patients with early (Ludwig stages 1 and 2) disease. After baseline, there was a small increase in HVPG over the next 5 years in most patients. In patients with precirrhotic PBC, 82% had portal hypertension and in 34% this was >12 mmHg. Portal pressure correlated significantly with a semiquantitative grading of cholestasis, interface hepatitis and portal tract and sinusoidal fibrosis. NRH was present in only 20% of wedge biopsies., Conclusions: Portal hypertension commences in the early stages of PBC, long preceding both rises in serum bilirubin and the development of cirrhosis. Around 34% of precirrhotic PBC patients have 'high-risk' portal hypertension, which is associated with lesions in the portal tracts and sinusoids rather than with NRH., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Hereditary causes of ovarian cancer include Lynch syndrome, which is due to inherited pathogenic variants affecting one of the four mismatch repair genes involved in DNA repair. The aim of this study was to evaluate tumour mismatch repair deficiency and prevalence of Lynch syndrome in high-risk women referred to the Manchester Centre for Genomic Medicine with ovarian cancer over the past 20 years., Methods: Women with ovarian cancer diagnosed before the age of 35 years and/or with a suggestive personal or family history of Lynch syndrome cancers underwent tumour testing with immunohistochemistry for mismatch repair deficiency and, where indicated, MLH1 promoter methylation testing followed by constitutional testing for Lynch syndrome., Results: In total, 261 ovarian cancers were tested and 27 (10.3%; 95% CI 6.9% to 14.7%) showed mismatch repair deficiency by immunohistochemistry. Three of 7 with MLH1 loss showed MLH1 promoter hypermethylation, and 18 of the remaining 24 underwent constitutional testing for Lynch syndrome. A further 15 women with mismatch repair proficient tumours underwent constitutional testing because of a strong family history of Lynch syndrome cancers. Pathogenic variants were identified in 9/33 (27%) women who underwent constitutional testing, aged 33-59 years (median 48 years), including one whose tumour was mismatch repair proficient. Most Lynch syndrome tumours were of endometrioid histological subtype., Conclusions: Tumour mismatch repair deficiency identified by immunohistochemistry is a useful prescreen for constitutional testing in women with ovarian cancer with personal or family histories suggestive of Lynch syndrome., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Key Content: Lynch syndrome is an autosomal dominant condition closely associated with colorectal, endometrial and ovarian cancer.Women with Lynch syndrome are at increased risk of both endometrial and ovarian cancer and should be offered personalised counselling regarding family planning, red flag symptoms and risk-reducing strategies.Surveillance for gynaecological cancer in women with Lynch syndrome remains controversial; more robust data are needed to determine its effectiveness.Universal testing for Lynch syndrome in endometrial cancer is being adopted by centres across Europe and is now recommended by the National Institute for Health and Care Excellence; thus, gynaecologists must become familiar with testing strategies and their results.Testing strategies involve risk stratification of cancers based on phenotypical features and definitive germline testing., Learning Objectives: To define the pathogenesis of Lynch syndrome and its associated gynaecological cancers.To understand the testing strategies for Lynch syndrome in women with gynaecological cancer.To learn how best to counsel women with Lynch syndrome regarding gynaecological cancer and risk-reducing strategies to enable informed decision-making., Ethical Issues: Offering gynaecological surveillance despite a lack of robust evidence for its clinical effectiveness may falsely reassure women and delay risk-reducing hysterectomy.Genetic testing may yield variants of unknown significance with ill-defined clinical implications, which can lead to confusion and anxiety.Genetic testing has implications not only for the individual, but also for the whole family, so expert counselling is crucial., (© 2021 The Authors. The Obstetrician & Gynaecologist published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.)

Aims: The role of liver biopsy in primary biliary cholangitis (PBC) is controversial, as is the optimal method of histological assessment. We compared the Ludwig and Ishak systems and three components of the Japanese (Nakanuma) staging system to evaluate their clinical and biochemical correlations and prognostic value., Methods: We reviewed biopsies from 106 patients with PBC, derived from a previous trial of colchicine therapy with 24-34 years' follow-up, following which five clinical outcomes were evaluated: hepatic decompensation, cholestatic PBC death/liver transplant, portal hypertensive PBC death, all PBC deaths and overall survival., Results: Ludwig and Ishak stages correlated well with prognostically significant parameters, including serum bilirubin, and both Mayo and Child Scores. Serum aspartate aminotransferase correlated with interface hepatitis (IFH), and alkaline phosphatase with orcein deposition, bile duct (BD) loss and cholestasis. Ludwig correlated with all five clinical outcomes, while Ishak stage was only significantly correlated with two. While sinusoidal fibrosis, orcein deposition, BD loss and cholestasis all predicted hepatic death/transplant, after correction for Mayo Score, the only histological parameters predictive of clinical outcomes were IFH (associated with two) and sinusoidal fibrosis (associated with all five)., Conclusion: Liver biopsy is required in the diagnosis of around 20% of patients with PBC. The Ludwig system is of more prognostic value than both Ishak and any of the three individual components of the Nakanuma staging system, but the major histological parameter providing independent prognostic value beyond the Mayo Score is sinusoidal fibrosis., Competing Interests: Competing interests: None., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The study sought to establish the feasibility and acceptability of anal screening among men MSM., Design: Prospective cohort study., Setting: Sexual health clinics in tertiary care., Patients: Known HIV-positive and negative MSM who have anoreceptive intercourse., Intervention: Anal screening with human papilloma virus (HPV) testing, liquid-based cytology and high-resolution anoscopy with biopsy of anoscopic abnormalities. Participants completed questionnaires at baseline and at 6 months., Results: Anal HPV was highly prevalent in MSM (HIV-positive, 88% and HIV-negative, 78%). Despite the high prevalence of cytological abnormality in both HIV-positive (46.2%) and negative (35.0%) MSM, almost half of anal intraepithelial neoplasia (AIN) of all grades were associated with negative cytology. Anoscopically directed biopsies detected AIN3 or worse (AIN3+) in 14 of 203 (6.9%) of HIV-positive MSM and three of 81 (3.7%) HIV-negative MSM. The corresponding prevalence of AIN2+ was 26.6 and 20.9%, respectively. One case of AIN3 was detected at the second visit. Screening was considered to be highly acceptable by participants., Conclusion: The high prevalence of high-risk-HPV and frequency of false negative cytology in this study suggest that high-resolution anoscopy would have most clinical utility, as a primary screening tool for anal cancer in a high-risk group. The prevalence of AIN3+ in HIV-positive MSM lends support for a policy of screening this group, but the high prevalence of lower grade lesions which do not warrant immediate treatment and the limitations of treating high-grade lesions requires careful consideration in terms of a screening policy.

Background and Aims: Lynch syndrome (LS) patients have DNA mismatch repair deficiency and up to 80% lifetime risk of colorectal cancer (CRC). Screening of mutation carriers reduces CRC incidence and mortality. Selection for constitutional mutation testing relies on family history (Amsterdam and Bethesda Guidelines) and tumour-derived biomarkers. Initial biomarker analysis uses mismatch repair protein immunohistochemistry and microsatellite instability. Abnormalities in either identify mismatch repair deficiency but do not differentiate sporadic epigenetic defects, due to MLH1 promoter region methylation (13% of CRCs) from LS (4% of CRCs). A diagnostic biomarker capable of making this distinction would be valuable. This study compared two biomarkers in tumours with mismatch repair deficiency; quantification of methylation of the MLH1 promoter region using a novel assay and BRAF c.1799T>A, p.(Val600Glu) mutation status in the identification of constitutional mutations., Methods: Tumour DNA was extracted (formalin fixed, paraffin embedded, FFPE tissue) and pyrosequencing used to test for MLH1 promoter methylation and presence of the BRAF c.1799T>A, p.(Val600Glu) mutation 71 CRCs from individuals with pathogenic MLH1 mutations and 73 CRCs with sporadic MLH1 loss. Specificity and sensitivity was compared., Findingss: Unmethylated MLH1 promoter: sensitivity 94.4% (95% CI 86.2% to 98.4%), specificity 87.7% (95% CI 77.9% to 94.2%), Wild-type BRAF (codon 600): sensitivity 65.8% (95% CI 53.7% to 76.5%), specificity 98.6% (95% CI 92.4% to 100.0%) for the identification of those with pathogenic MLH1 mutations., Conclusions: Quantitative MLH1 promoter region methylation using pyrosequencing is superior to BRAF codon 600 mutation status in identifying constitutional mutations in mismatch repair deficient tumours., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The c-Jun N-terminal protein kinase (JNK) and its two direct activators, namely the mitogen-activated protein kinase (MAPK) kinase 4 (MKK4) and MKK7, constitute a signaling node frequently mutated in human pancreatic ductal adenocarcinoma (PDAC). Here we demonstrate the cooperative interaction of endogenous expression of Kras(G12D) with loss-of-function mutations in mkk4 or both, mkk4 and mkk7 genes in the pancreas. More specifically, impaired JNK signaling in a subpopulation of Pdx1-expressing cells dramatically accelerated the appearance of Kras(G12D)-induced acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasias, which rapidly progressed to invasive PDAC within 10 weeks of age. Furthermore, inactivation of mkk4/mkk7 compromised acinar regeneration following acute inflammatory stress by locking damaged exocrine cells in a permanently de-differentiated state. Therefore, we propose that JNK signaling exerts its tumor suppressive function in the pancreas by antagonizing the metaplastic conversion of acinar cells toward a ductal fate capable of responding to oncogenic stimulation., (©2014 American Association for Cancer Research.)

Context: Microvascular thrombosis is a critical event in severe acute pancreatitis. Human recombinant activated protein C (Xigris®, Eli Lilly, Indianapolis, IN, USA) modulates the interplay between pro-inflammatory and pro-coagulant pathways and maintains microvascular patency. However, the anticoagulant properties of Xigris® may precipitate bleeding from the inflamed pancreas., Objective: This study tests the hypothesis that Xigris® can ameliorate experimental acute pancreatitis without causing pancreatic haemorrhage., Methods: Sprague Dawley rats were allocated as follows: Group 1: control (n=7); Group 2: acute pancreatitis (n=6); Group 3: administration of Xigris® 500 µg/kg body weight before induction of acute pancreatitis (n=6); and Group 4: Administration of Xigris® 500 µg/kg body weight 30 minutes after induction of acute pancreatitis (n=6). Acute pancreatitis was induced by intraperitoneal administration of L-arginine 300 mg/100 g body weight. Animals were sacrificed at 48 hours and biochemical, haematological, and histological markers of pancreatic haemorrhage and inflammation assessed., Results: Median lipase in animals with acute pancreatitis was 10 U/mL (range: 7-16 U/mL) compared to 5.5 (range: 3-8 U/mL) in controls (P=0.028). Lipase was also elevated in animals given Xigris® both before (12 U/mL, range: 8-22 U/mL; P=0.031 vs. control group) and after (46 U/mL, range: 9-71 U/mL; P=0.015 vs. control group) induction of acute pancreatitis). Haemoglobin levels were similar among all groups (P=0.323). There was no histological evidence of pancreatic haemorrhage in animals treated with Xigris®. Pre-treatment with Xigris® was associated with a significant reduction in pancreatic injury. This effect was absent when Xigris® was administered after induction of acute pancreatitis., Conclusion: Xigris® did not lead to pancreatic haemorrhage in experimental acute pancreatitis. Administration of Xigris® prior to induction of acute pancreatitis was associated with amelioration of injury. This effect was not seen with administration of Xigris® after induction of acute pancreatitis.

Aims. To compare methylation profiles, protein expression, and microsatellite instability (MSI) of sporadic, HNPCC, and familial hyperplastic polyps (HPs). Methods. Methylation-specific PCR (MSP) and pyrosequencing assessed p16, MGMT, hMLH-1, MINT 1, and MINT 31 methylation. IHC (Immunohistochemistry) assessed Ki67, CK20, hMLH-1, hMSH-2, and hMSH-6 protein expression. MSI analysis was performed on those polyps with adequate DNA remaining. Results. 124 HPs were identified 78 sporadic, 21 HNPCC, 25 familial, and the HNPCC group demonstrated no significant differences in overall methylation (P = .186 Chi(2)). The familial group demonstrated significantly less over all methylation levels (P = .004 Chi(2)). Conclusions. HPs that occur in HNPCC have no more worrying features at a molecular level than those patients with HPs in a sporadic setting.

Macrofouling by zebra mussels (Dreissena polymorpha) has serious environmental, economic and legal consequences for freshwater shipping and raw water facilities. Current antifouling technologies, such as organometallics or aggressive oxidisers, have negative environmental impacts limiting their application. As part of an effort to discover antifoulants with a reduced environmental footprint, the endocannabinoid, anandamide and nine other compounds sharing structural or functional features were tested for their ability to inhibit zebra mussel byssal attachment. A byssal attachment bioassay identified six efficacious compounds; four compounds also had no negative impact on mussels at concentrations maximally inhibiting byssal attachment and three of them had no significant cumulative toxicity towards a non-target organism, Daphnia magna. This discovery demonstrates that both naturally occurring and synthetic cannabinoids can serve as non-toxic efficacious zebra mussel antifoulants. Applications with this technology may lead to a new genre of cleaner antifoulants, because the strategy is to prevent attachment rather than to poison mussels.

Objective: To determine follow-up requirements following transanal endoscopic microsurgery (TEM) for rectal tumours based on clinical and histopathological assessment of resection specimens., Method: A consecutive series of 117 patients undergoing TEM between 1997 and 2005 was studied. The excised specimens were classified as intact with clear surgical resection margins, macroscopically intact specimens with microscopically involved resection margins or piecemeal. Recurrence rates were determined for the three groups., Results: Of the 117 procedures performed, 80 were for benign disease and 37 for malignancy. Within the benign group 39 (49%) resections were intact with clear surgical resection margins and yielded zero recurrences; 22 (27%) resections were macroscopically intact with microscopically involved surgical resection margin and yielded two recurrences; and 19 (24%) resections were piecemeal and yielded eight recurrences. Within the malignant group all 37 patients had resection specimens which were intact with clear surgical resection margins. Two patients had immediate salvage surgery. Of the 35 who went on to long-term follow-up post-TEM (0.6-8.1 years, median 4) four developed recurrent cancer (two local with submucosal disease and two liver metastases)., Conclusion: For benign rectal neoplasms, resection of an intact specimen with histologically clear surgical resection margins was associated with no observed mucosal recurrence. Local recurrence after TEM is significantly more frequent when histological examination reveals involved margins or when resection is piecemeal. Early endoscopic follow up is required for the latter two groups. Local recurrence for malignant cases was submucosal and detected by palpation.

Macrofouling of aquatic man-made structures by zebra mussels (Dreissena polymorpha) poses significant economic burdens on commercial freshwater shipping and facilities utilising raw water. The negative environmental impact of some current antifouling technologies has limited their use and prompted investigation of non-organometallic and non-oxidising antifoulants as possible environment-friendly alternatives. The plant-derived natural product capsaicin and 18 other compounds with one or more capsaicin-like structural features were tested for their potential to inhibit zebra mussel byssal attachment at a single high concentration of 30 microM. Of these, three compounds displaying the highest levels of attachment inhibition where selected for further concentration-response testing. This testing revealed that capsaicin (8-methyl-N-vanillyl-trans-6-nonenamide), N-vanillylnonanamide, and N-benzoylmonoethanolamine benzoate all inhibited byssal attachment with potency values (EC(50)) in the micromolar range. None of these compounds were lethal to adult specimens of the water flea, Daphnia magna, at concentrations that inhibited mussel byssal attachment.

Objectives: This study aims to identify plaque neovascularisation using antibodies to CD31, CD105 and TGFbeta1, and to compare their patterns of expression., Methods: Tissue expression of CD31, CD105 and TGFbeta1 was examined immunohistologically in atherosclerotic plaques from 53 patients who had undergone carotid endarterectomy and in 10 controls., Results: CD31 was observed in a proportion of the microvessels within atheroma. The expression of CD105 was barely visible in normal arteries, but was markedly enhanced in atherosclerotic plaques. The vast majority of the microvessels in atheroma were positive for CD105 with pronounced expression around the periphery of the lipid core. In consecutive sections, microvessels showing negative staining for CD31 were positive for CD105. Although TGFbeta1 was seen in the thickened intima, it was more strongly expressed in well-formed fibrous plaques. Consecutive sections showed that some microvessels were stained by both CD105 and TGFbeta1, but in certain areas microvessels were exclusively CD105 positive., Conclusions: These observations highlight the distinctive expression patterns of CD31, CD105 and TGFbeta1, suggesting their specific roles in the development of atherosclerotic plaques. CD105 is almost universally expressed in microvessels within the atheroma and is therefore a better vascular marker than CD31 and TGFbeta1for assessing neovascularisation in atherosclerotic plaques.

Context: Radiofrequency ablation of pancreatic tumours carries a risk of injury to important structures such as the bile duct and duodenum. We have recently developed an ex-vivo model of radiofrequency ablation of the porcine pancreas., Objective: This study evaluates the effect of variations in probe temperature, duration of ablation and simulated portal venous flow on radiofrequency-induced injury. SPECIMEN RETRIEVAL: Pancreata of 30 6-month-old healthy pigs undergoing sacrifice in a commercial abattoir were used., Interventions: Radiofrequency energy was applied to a pre-marked area of the pancreatic head. Pancreatic head biopsies were taken after ablation to incorporate duodenum, portal vein and bile duct respectively and frozen in liquid nitrogen. For each experiment a portion of the tail of the pancreas was studied as non-ablated control. Paired slides using haematoxylin and eosin (H&E) and nicotinamide adenine dinucleotide (NADH) stains were prepared., Main Outcome Measures: The effects of variation in target temperature (100 degrees C to 80 degrees C), duration of ablation and of simulated portal perfusion were studied., Results: Optimal thermal kinetic characteristics were produced by a target temperature of 90 degrees C applied for 5 minutes. At this temperature there was ablation of pancreas without injury to adjacent viscera. Higher temperatures resulted in injury to the bile duct and portal vein. Simulated portal circulation had no effect on ablation., Conclusions: In this ex-vivo study radiofrequency produced a temperature and duration dependent ablation with the optimal characteristics being 90 degrees C for 5 minutes.

Objectives: The aim of this study was to develop and validate an ex vivo model for the assessment of radiofrequency (RF) ablation of the pancreas., Methods: Porcine pancreata were used within 1 hour of sacrifice. RF was delivered to a premarked area in the center of the pancreatic head using a thermocouple-tipped multiprobe array. Four temperature presets were evaluated: 70 degrees-100 degrees C in 10 degrees increments. Immediately after ablation serial sections of the pancreatic head were cut to incorporate duodenum, portal vein, and bile duct. For each experiment, a portion of pancreatic tail was sampled as nonablated control. Hematoxylin and eosin (H&E) slides together with nicotinamide adenine dinucleotide (NADH) stained preparations were made. The NADH staining was quantified using computerized digital image recognition techniques., Results: Control sections (n = 20) demonstrated normal pancreatic architecture on H&E and strong NADH staining indicating preserved tissue oxidative metabolism. RF produced a temperature-dependent destruction of parenchymal architecture (H&E) with a corresponding loss of NADH activity. There was no evidence of thermal injury to the duodenum. Quantification of NADH staining demonstrated a median positive staining of 69.26% (55.87-97.28) for control tissue compared with 1.40% (0-7.77) for ablated pancreas (P < 0.001; Mann-Whitney U test)., Conclusion: This study describes the development of a relatively simple, reliable, and reproducible model for evaluation of RF ablation of pancreatic parenchyma.

Autoimmune hepatitis (AIH) is a chronic liver disease of unknown aetiology characterized by circulating autoantibodies, hyperglobulinaemia and interface hepatitis. The mechanisms of progression from initial autoimmune attack to fibrosis and cirrhosis are unclear but oxidant stress may be involved. Markers of lipid peroxidation, antioxidant status, hepatic fibrogenesis and liver function were measured in blood and urine in 35 controls and in 33 patients with type-1 AIH; histology was assessed in 18 patients. In AIH, markers of lipid peroxidation were significantly elevated (8-isoprostane in both plasma and urine P < 0.001; plasma malondialdehyde P = 0.017). Total antioxidant capacity in protein-free serum and total glutathione in both whole blood and plasma were significantly reduced (P = 0.007, P = 0.037, P < 0.001, respectively). The antioxidants selenium, vitamin A and vitamin E were significantly decreased (P = 0.007, P < 0.001, P = 0.025, respectively); vitamin C was unchanged. Urinary 8-isoprostane correlated positively with interface hepatitis and necroinflammatory score and with hepatic fibrogenesis (type III procollagen peptide). Interface hepatitis correlated negatively with vitamin A and whole blood total glutathione. Oxidant stress, as reflected in blood and urine by a wide range of pro- and antioxidant markers, is a significant feature of AIH and provides a probable mechanism linking hepatic necroinflammation to fibrogenesis and disease progression.

Aims: Prostaglandins produced by the action of cyclooxygenases (COX) are important mediators of systemic vasodilatation and inflammation in liver cirrhosis. The aim of this study was to investigate the distribution of COX-1 and COX-2 in postviral cirrhosis., Methods: The immunohistochemical expression of the constitutive (COX-1) and the inducible (COX-2) isoenzymes was investigated in 15 patients with cirrhosis after hepatitis B and C infection; three normal control livers were also analysed., Results: COX-2 was absent from normal liver but was highly expressed in cirrhosis, mainly in the inflammatory, sinusoidal, vascular endothelial, and biliary epithelial cells. Low amounts of COX-1 were expressed in both normal and cirrhotic livers, exclusively in sinusoidal and vascular endothelial cells, with no differences seen between normal and cirrhotic livers., Conclusions: COX-2 is overexpressed in liver cirrhosis, and possibly contributes to prostaglandin overproduction, which may be a major component of the inflammation and hyperdynamic circulation associated with cirrhosis. Because COX-2 is thought to contribute to tumour development, high COX-2 production could be a contributor to hepatocellular carcinoma development in cirrhosis. The finding of COX-2 and not COX-1 upregulation in cirrhosis could provide a possible new role for selective COX-2 inhibitors in reducing inflammation and minimising the occurrence of hepatocellular carcinoma in patients with cirrhosis.

Allocation of organic carbon (OC) to primary energetic pathways was estimated under seasonal and artificially elevated ambient temperatures for a field population of a freshwater pulmonate snail, Physella virgata. Allocation to respiration increased with temperature. Snails allocated most assimilated OC to reproduction within their natural temperature range (15 degrees -35 degrees C), where assimilation efficiencies remained relatively stable at 25%-35%. However, in artificially heated waters exceeding 35 degrees C, declining assimilation rates and increasing respiratory demands inhibited allocation to reproduction and growth. At the species' 40 degrees C upper thermal limit, assimilation efficiencies fell below 10%, while average consumption levels more than doubled relative to snails unaffected by the thermal effluent. Ambient temperature substantially influenced OC allocation over P. virgata's natural temperature range and negatively affected growth and reproduction at temperatures approaching or exceeding maximum natural levels.

The effects of temperature acclimation, acute temperature variation and progressive hypoxia on oxygen consumption rates (VO2) were determined for the zebra mussel Dreissena polymorpha. In the first experiment, after acclimation to 5, 15 or 25 degrees C for at least 2 weeks, VO2 was determined at 5 degrees C increments from 5 to 45 degrees C. VO2 increased in all three acclimation groups from 5 to 30 degrees C, corresponding to the normal ambient temperature range for this species. Mussels displayed imperfect temperature compensation at temperatures above 15 degrees C, but exhibited little acclimatory ability below 15 degrees C. In the hypoxia experiment, VO2 was determined over the course of progressive hypoxia, from full saturation (oxygen tension [PO2]=160 Torr [21.3 kPa]) to a PO2 at which oxygen uptake ceased (<10 Torr [1.3 kPa]). Mussels were acclimated to either 5, 15 or 25 degrees C for at least 2 weeks and their respiratory response to progressive hypoxia was measured at three test temperatures (5, 15 and 25 degrees C). The degree of oxygen regulation increased with increasing test temperature, particularly from 5 to 15 degrees C, but decreased with increasing acclimation temperature. The decreased metabolic rate observed for warm-acclimated animals, particularly in the upper portion of the temperature range of the zebra mussel, may allow for conservation of organic energy stores during warm summer months. Compared to other freshwater bivalves, D. polymorpha is a relatively poor oxygen regulator, corresponding with its preference for well-oxygenated aquatic habitats. In addition, a new quantitative method for determining the degree of oxygen regulation is presented.

Divalent metal transporter1 (DMT1; also known as DCT1 or NRAMP2) is an important component of the cellular machinery responsible for dietary iron absorption in the duodenum. DMT1 is also highly expressed in the kidney where it has been suggested to play a role in urinary iron handling. In this study, we determined the effect on renal DMT1 expression of feeding an iron-restricted diet (50 mg/kg) or an iron-enriched diet (5 g/kg) for 4 wk and measured urinary and fecal iron excretion rates. Feeding the low-iron diet caused a reduction in serum iron concentration and fecal iron output rate with an increase in renal DMT1 expression. Feeding an iron-enriched diet had the converse effect. Therefore, DMT1 expression in the kidney is sensitive to dietary iron intake, and the level of expression is inversely related to the dietary iron content. Changes in DMT1 expression occurred intracellularly in the proximal tubule and in the apical membrane and subapical region of the distal convoluted tubule. Increased DMT1 expression was accompanied by a decrease in urinary iron excretion rate and vice versa when DMT1 expression was reduced. Together, these findings suggest that modulation of renal DMT1 expression may influence renal iron excretion rate.

Background: We have previously shown that the rat kidney reabsorbs metabolically significant amounts of iron and that it expresses the divalent metal transporter 1, DMT1. The Belgrade (b) rat carries a mutation in DMT1 gene, which causes hypochromic, microcytic anemia due to impaired intestinal iron absorption and transport of iron out of the transferrin cycle endosome. In the duodenum of b/b rats, expression of DMT1 mRNA and protein is increased, suggesting a feedback regulation by iron stores. The aim of this study was to investigate iron handling and DMT1 expression in the kidneys of Belgrade rats., Methods: Animals were maintained for 3 weeks on a synthetic diet containing 185 mg/kg iron (FeSO4), after which functional and molecular parameters were analyzed in male heterozygous (+/b) and homozygous (b/b) rats (N = 4 to 6 for each group)., Results: Serum iron concentration was significantly higher in b/b compared to +/b rats while urinary iron excretion rates were unchanged in b/b compared to +/b rats. Northern analysis using a rat DMT1 probe showed comparable mRNA levels between +/b and b/b animals. Western analysis and immunofluorescence microscopy performed using a polyclonal antibody against rat DMT1 showed that DMT1-specific immunoreactivity was almost absent in the kidneys of b/b rats compared to that seen in +/b animals., Conclusion: Our results indicate that the G185R mutation of DMT1 causes protein instability in the kidneys of b/b rats. Given that +/b and b/b rats excrete comparable amounts of iron, the lack of DMT1 protein is compensated by an alternative, yet to be identified, mechanism.

Several mediators of systemic vasodilatation in liver cirrhosis have been reported. Among these is nitric oxide (NO), which has been proposed as one of the main mediators. In this study, sera and liver biopsies were analysed from 15 patients with clinically and pathologically diagnosed liver cirrhosis. In addition, sera from seven and liver biopsies from three healthy controls were used. Serum levels of nitrite (the end product of NO) were measured using the Griess reaction and the expression of the inducible nitric oxide synthase (iNOS) and constitutive nitric oxide synthase (ecNOS) proteins was investigated using immunohistochemistry. This study shows that serum nitrite levels (94 +/- 9.8 micro mol/l) in cirrhotic patients were significantly (p < 0.05) increased in comparison with the controls (36.6 +/- 11.03 micro mol/l). iNOS was completely absent from the control group but was highly expressed in the livers from the cirrhotic group. iNOS was seen mainly in the inflammatory cells infiltrating the portal tracts, blood monocyte-like cells, hepatocytes, sinusoidal cells, and endothelial cells. However, expression of ecNOS was only seen in the vascular endothelial cells of both the control and the cirrhotic groups, but was much higher in the latter. It is therefore clear that NO is augmented in cirrhotic patients and it is mainly produced by induction of iNOS. Moreover, NO up-regulation is dependent on the inflammatory stage of liver cirrhosis. ecNOS production could be a normal chronic adaptation mechanism of the endothelium to the chronically increased splanchnic blood flow secondary to portal hypertension. In the near future, the appropriate inhibition of NO activity by using NOS-active agents may provide a novel strategy for the treatment of patients with liver cirrhosis., (Copyright 2003 John Wiley & Sons, Ltd.)

Primary biliary cirrhosis (PBC) is a chronic cholestatic disorder characterised by an immunological, and often granulomatous, attack on bile ducts leading to fibrosis, cirrhosis, liver failure and death. Animal and human studies suggest that oxidant stress plays a key role in progression of other liver diseases, but no comprehensive investigation has been performed previously in PBC. A wide range of lipid peroxidation and antioxidant markers were measured in the blood and urine of 41 patients with histologically confirmed PBC. Lipid peroxidation markers were significantly elevated [plasma and urinary 8-isoprostane, P<0.001; plasma malondialdehyde (MDA), P=0.007] compared to age- and sex-matched controls. The most striking antioxidant depletion occurred with plasma total glutathione where levels were significantly reduced (30% of controls). Total serum antioxidant levels were decreased (P=0.013) and serum selenium and vitamin A were also lower (both P<0.001); vitamins C and E were normal. Most patients had early disease biochemically and were Child-Pugh grade A. Urinary 8-isoprostane correlated positively with Ludwig stage and markers of hepatic injury and cholestasis. This study clearly demonstrates that oxidant stress, as reflected in a comprehensive spectrum of lipid peroxidation and antioxidant markers, is a significant feature of early-stage PBC.

Aims: To study the expression of Ki-67 and cytokeratin 20 (CK20) in a group of hyperplastic polyps (including a group with "atypical" features) with the aim of determining whether upper crypt Ki-67 staining and lower crypt CK20 staining correlated with these atypical features, as assessed by light microscopy., Methods: Fifty seven formalin fixed, paraffin wax embedded hyperplastic colorectal polyps from 53 patients were selected on histological grounds; these comprised 26 typical polyps and 31 with atypical features, which included nuclear hyperchromatism, basal crowding, and increased mitotic activity. These polyps were examined using a standard immunohistochemical method with antibodies against CK20 and Ki-67. Comparisons were made with normal mucosa, adenomatous polyps, and carcinomas., Results: Of the 26 typical polyps, 17 showed the usual pattern of lower crypt Ki-67 and upper crypt CK20 staining; one with upper crypt Ki-67 staining but normal surface CK20 staining; seven with Ki-67 confined to the lower half of crypts but with scattered lower crypt CK20; and one with both upper crypt Ki-67 staining, together with scattered CK20 basal staining. Of the 31 polyps with atypical features, 11 showed the usual staining pattern of lower crypt Ki-67 staining and surface staining with CK20; two showed Ki-67 staining extending into the upper half of crypts, but with a normal surface staining with CK20; 14 showed Ki-67 confined to the lower half of crypts, but scattered lower crypt staining with CK20; and four showed upper crypt Ki-67 staining together with scattered CK20 lower crypt staining., Conclusions: The normal pattern of lower crypt Ki-67 and upper crypt CK20 was seen in 28 of the 57 hyperplastic polyps and, in general, this corresponded with standard light microscopic appearances. Twenty one of the 57 polyps showed lower crypt mosaic CK20 staining, which in general corresponded with basal abnormalities on light microscopy, although seven specimens had normal appearances. Two smaller subsets emerged, one showing upper crypt Ki-67 staining in the presence of normal CK20 expression (three cases) and another in which a combination of lower crypt CK20 and upper crypt Ki-67 expression was seen (five cases). This last pattern was similar to that of neoplastic polyps and raises the possibility that a subgroup of hyperplastic polyps exists that may be a variant with malignant potential. Further studies with markers of mismatch repair genes and K-ras mutations may help to clarify this issue.

Background: Recent evidence suggests that the brain weight of individuals over the age of 60 who commit suicide is significantly higher than in those who die of natural causes., Aims: To ascertain whether brain weight is different in people of a younger age who commit suicide than in those who die accidentally., Method: A retrospective review of post-mortem reports collecting height, weight and brain weight in 100 suicide victims (87 males, mean age 38.5 years) and 100 age/gender-matched controls who died accidentally or of natural causes (87 males, mean age 38.7 years). Comparison by t-test was made of brain weight in isolation as well as brain weight corrected for height, weight and body mass index., Results: These results reveal no significant difference in brain weight in suicide cases compared to the general population (P > 0.05). The brain weight of those who died by hanging was significantly higher than of those who died by overdose., Conclusions: Whatever the significant neuropsychiatric elements are that influence suicidal behaviour, they do not consistently affect brain weight in the population studied.

Background/aims: Chronic hepatitis C infection is a major world-wide problem, frequently progressing to cirrhosis, liver failure or hepatoma. The pathological mechanisms of disease progression are unclear but oxidant stress may play a role., Methods: Markers of lipid peroxidation, antioxidant status, hepatic fibrogenesis and liver function were measured in blood or urine from 42 chronic hepatitis C patients. Fibrosis was graded histologically in a subgroup of 33 patients., Results: The lipid peroxidation marker 8-isoprostane and the ratio of oxidized to reduced glutathione were significantly elevated (P<0.001, P=0.006). The antioxidants glutathione, selenium and vitamins A, C and E were significantly decreased (all P<0.001) compared to age and sex matched controls. Abnormal values were more marked in cirrhotics, but significant changes were also observed in the non-cirrhotic group. The fibrosis score correlated positively with urinary 8-isoprostane and type III procollagen peptide and negatively with vitamin A., Conclusions: Oxidant stress, as reflected in blood and urine by a wide range of pro- and antioxidant markers, is a significant feature of hepatitis C infection. Although more severe in the cirrhotic group, there was clear evidence of oxidant stress in non-cirrhotic patients. Antioxidant therapy may therefore have a role in slowing disease progression to cirrhosis.

Hepatitis C virus (HCV) is a major cause of chronic hepatitis with liver-related death occurring in 20-25% of patients who develop cirrhosis. Detection of the virus RNA in liver is difficult since viral expression is very low. In situ polymerase chain reaction (PCR) in situ hybridisation (ISH) was developed for detection and localisation of viral RNA in formalin-fixed, paraffin-embedded liver tissue. Nested PCR technology was adapted for in situ use employing primers derived from the 5' end of the HCV genome. Seventeen liver blocks from known HCV-infected patients were examined. Viral RNA was detected in liver from eleven patients using solution phase reverse transcriptase-PCR. Of these positive samples, ten were positive by the in situ method. Positive signal was detected in the cytoplasm of hepatocytes and mononuclear cells. No Kupffer cell or bile duct epithelial positivity was observed. No positive signal was evident in any of the negative controls. A reliable method is described to demonstrate the presence and localisation of HCV RNA in liver tissue using an in situ PCR-ISH assay and it is believed that this will be a valuable tool for the understanding of HCV replication and pathogenesis.

Purpose: Colonic ischemia after aortic surgery is associated with increased mortality and morbidity rates. This study was conducted as a single-center side arm to a multicenter, randomized, placebo-controlled study to evaluate the effect of dopexamine hydrochloride on its incidence., Methods: Thirty patients, mean age 65.1 years (range, 46-84), undergoing elective infrarenal aortic surgery were entered. Preoperative hemodynamic and respiratory parameters were optimized. Patients were then randomly assigned to receive a perioperative infusion of dopexamine at 2 microg/kg per minute (n = 12) or 0.9% saline placebo (n = 18). All patients underwent colonoscopy and biopsy preoperatively and 1 week postoperatively. Specimens were assessed for evidence of mucosal ischemia, presence of mast cell tryptase, myeloperoxidase activity, and both the inducible and endothelial isoforms of nitric oxide synthase., Results: There was no significant difference in perioperative fluid and blood requirements or hemodynamic and respiratory parameters between the two groups. However, there was significantly less evidence of mucosal ischemic changes in dopexamine-treated patients (n = 1) compared with placebo (n = 8) (P =.049). Furthermore, when preoperative biopsies were compared with those performed 1 week postoperatively, nine (50%) patients in the placebo group and two (16.7%) in the dopexamine group scored worse. Although there was no significant difference in inflammatory markers between the two groups, both mast cell tryptase and myeloperoxidase expression were increased in patients with histologic evidence of ischemia (P <.05). Furthermore, inducible nitric oxide synthase staining within the vascular (P =.001) and lamina propria (P <.05) components of the mucosa was also significantly greater., Conclusion: A perioperative dopexamine infusion affords significant histologic protection to colonic mucosa after aortic surgery.

Antioxidant and antifibrotic properties of colchicine were investigated in the carbon tetrachloride (CCl(4)) rat model. (1) The protective effect of colchicine pretreatment on CCl(4) induced oxidant stress was examined in rats subsequently receiving a single lethal dose of CCl(4). Urinary 8-isoprostane, kidney and liver malondialdehyde and kidney glutathione levels increased following CCl(4) treatment, but only the rise in kidney malondialdehyde was significantly inhibited by colchicine pretreatment. Serum total antioxidant levels were significantly higher in the colchicine pretreatment group. (2) The long term effects of colchicine treatment on CCl(4) induced liver damage were investigated using liver histology and biochemical markers (hydroxyproline and type III procollagen peptide). Co-administration of colchicine with sub-lethal doses of CCl(4) over 10 weeks did not prevent progression to cirrhosis. However, rats made cirrhotic with repeated CCl(4) challenge and subsequently treated with colchicine for 12 months, all showed histological regression of cirrhosis. (3) The antioxidant effect of colchicine in vitro was evident only at very high concentrations compared to other plasma antioxidants. In summary, colchicine has only weak antioxidant properties, but does afford some protection against oxidative stress; more importantly, long term treatment with this drug may be of value in producing regression of established cirrhosis.

The synchronous presentation of a primary renal adenocarcinoma and contralateral uretic metastasis is discussed. The pattern of immunohistochemical staining confirmed that the contralateral ureteric obstruction was the result of a metastasis from the primary renal adenocarcinoma.

Objective: To evaluate the effect of dopexamine on the incidence of acute inflammation in the stomach/duodenum in patients undergoing abdominal surgery > or =1.5 hrs with a minimum of one high-risk criterion., Design: Prospective, randomized, double-blind, placebo-controlled study. This study was conducted as a side arm to a multicenter, multinational study., Setting: University hospital in an adult intensive care unit., Patients: Thirty-eight patients., Interventions: Patients were stabilized with fluid, blood products, and supplementary oxygen to achieve predetermined goals: cardiac index > 2.5 L/min/m2, mean arterial blood pressure of 70 mm Hg, pulmonary arterial occlusion pressure of 10 mm Hg, hemoglobin of 100 g/L, and arterial saturation of 94%. After stabilization, the study drug (either placebo [group A], dopexamine 0.5 microg/kg/min [group B], or dopexamine 2.0 microg/kg/min [group C]) was commenced. The study drug infusion was started 2 to 12 hrs before surgery and infused for 24 hrs after surgery. Estimation of upper gut blood flow was assessed using a gastric tonometer, and gastroscopy with biopsy was performed before surgery (after induction of anesthesia) and 72 hrs after surgery. Comparisons were made between endoscopic findings and histologic proof of acute inflammatory changes. In addition, biopsies were assessed for the presence in the mucosa of mast cells, myeloperoxidase activity, and inducible nitric oxide synthase., Measurements and Main Results: Intramucosal pH decreased significantly with time in all three groups (p < .001), reaching the lowest point at the end of surgery. There was no difference among the groups. Endoscopy visualized acute inflammatory changes in 58.3% of group A patients, 46.2% of group B patients, and 53.90% of group C patients after hemodynamic optimization. At 72 hrs, dopexamine-treated patients compared with placebo-treated patients had a significantly lower incidence of gastric and duodenal acute inflammatory changes, as defined by myeloperoxidase activity (37.5% in groups B and C vs. 86% in group A; p < .05)., Conclusion: Dopexamine in doses of 0.5 and 2.0 microg/kg/min affords significant histologic protection to the upper gastrointestinal tract mucosa 72 hrs after operation in high-risk surgical patients undergoing abdominal surgery.

BACKGROUND: Mechanisms involved in the development of colon- ic ischaemia are not fully understood and there are conflicting reports regarding predisposing factors. The aim of this study was to evaluate the effect of dopexamine hydrochloride on the incidence of colonic ischaemia following aortic surgery and to correlate immunohistochemical markers of inflammatory activation in its pathogenesis. METHODS: Thirty patients, of mean age 65 (range 46-84) years, undergoing elective infrarenal aortic surgery were randomized to receive a perioperative infusion of either dopexamine 2 &mgr;g kg-1 min-1 (n = 12) or 0.9 per cent saline placebo (n = 18). All patients underwent colonoscopy and biopsy following induction of anaesthesia and at 1 week after operation. Sections were stained with haematoxylin and eosin, and for mast cell tryptase (MCT), myeloperoxidase (MPO) and both the inducible (iNOS) and endothelial (eNOS) isoforms of nitric oxide synthase. Sections were analysed blindly and independently by two histopathologists. Patient and operative data were collected and stored separately. RESULTS: Colonic ischaemia was noted in nine patients based on microscopic findings. Endoscopy alone had a sensitivity of 56 per cent. There was a significantly lower incidence of colonic ischaemia in patients receiving dopexamine compared with placebo (P < 0.05). One death resulted from colonic infarction in the placebo group 11 days after operation. There was increased MPO and MCT expression in patients with histological evidence of ischaemia (P < 0.05); iNOS staining within the vascular (P = 0.001) and lamina propria (P < 0.05) components of the mucosa was also significantly greater. No association was found with eNOS. CONCLUSION: Perioperative dopexamine infusion confers a degree of protection to colonic mucosa following aortic surgery, possibly through an anti-inflammatory effect.

Background: Chronic liver disease is characterised by excessive deposition of collagen and other extracellular matrix proteins, produced mainly, but not exclusively, by activated hepatic stellate cells in the perisinusoidal space. In primary biliary cirrhosis (PBC) fibrosis is concentrated mainly around the portal tracts., Aims: To examine the hypothesis that, in addition to hepatic stellate cells, portal tract fibroblasts might play a significant role in the deposition of collagen in PBC., Methods: Fifty liver biopsy specimens from patients with PBC were studied. An in situ hybridisation technique was adapted to localise and measure semiquantitatively type I procollagen mRNA in formalin fixed, paraffin wax embedded sections, using an 35S labelled cRNA probe specific for the alpha 1 chain of rat type I procollagen. Hepatic fibrogenic activity was also assessed using serum type III procollagen peptide (PIIINP)., Results: In PBC, type I procollagen gene expression was significantly increased. Signal was localised mainly in and around inflamed portal tracts, to cells which had the appearances of portal fibroblasts. Signal activity in these cells correlated with the degree of portal fibrosis and inflammation and also with serum PIIINP concentrations., Conclusions: Results are consistent with the hypothesis that the excessive extracellular matrix, deposited within the liver in PBC, is synthesised not only by hepatic stellate cells but also by portal tract fibroblasts. The semiquantitative assessment of procollagen mRNA in liver biopsy specimens may provide a useful method of evaluating the rate of synthesis of collagen and therefore disease activity in patients with PBC.

Background: Colonic ischaemia is a well documented complication of abdominal aortic reconstruction. In this prospective study patients had routine preoperative and postoperative colonoscopy and biopsy, in order to determine the true incidence and implications., Methods: Fifty-six patients undergoing elective infrarenal aortic surgery, 28 for aneurysm and 28 for occlusive disease, had colonoscopy and biopsy before and 1 week after operation., Results: Colonic ischaemia was identified histologically in biopsies from 16 (30 per cent) of 53 patients. Almost half the patients had normal macroscopic appearances. Two factors exhibited a statistically significant association with the development of ischaemia: prolonged cross-clamp time (P < 0.05) and postoperative diarrhoea (P< 0.001). Co-morbidity was much higher in patients with colonic ischaemia (P< 0.005). Overall morbidity was significantly greater in the aneurysm group (P < 0.05)., Conclusion: Colonic ischaemia is common after aortic reconstruction. When suspected, colonoscopy with biopsy is diagnostic.

Adenocarcinomas of the urinary bladder are rare (1-5% of bladder tumours) and of notoriously poor prognosis. About one third of such tumours arise in urachal remnants related to the bladder. This is believed to be the first report of in situ change in the urachal remnant. The patient presented with mucusuria and computed tomography showed a typical urachal cyst. After excision the cyst was found to contain mucinous adenomatous epithelium but without invasion of the basal lamina. Pathological stage is the best prognostic indicator in urachal tumours. Prompt investigation and management of mucusuria may allow the diagnosis of urachal tumours in this preinvasive stage.

Ulcerative colitis is associated with abnormalities of mucin synthesis and secretion, features that may also be associated with malignant change. It has been shown that South Asians in Britain have a high incidence of ulcerative colitis but a low incidence of colorectal carcinoma compared with their European counterparts. Previous studies have demonstrated changes in colonic mucin sialylation and sulphation in both South Asian and European cases with ulcerative colitis. This was related to disease severity, but changes were also found in quiescent disease. The aim of the present study was to determine glycoconjugate expression in the colon from South Asian cases and to compare results with those from a group of affected Europeans. Glycans were identified in formalin-fixed, paraffin-embedded tissue from 17 South Asian patients with ulcerative colitis and from 11 European patients with a similar degree of colitis, by the application of 10 biotinylated lectins. These were directed against a range of sialyl, fucosyl and 2-deoxy, 2-acetamido-galactosyl sequences, using an avidin-peroxidase revealing system and semiquantitative assessment. The South Asian group showed a reduction in the binding of agglutinins from Sambucus nigra in the apical-membranous region of enterocytes, and a decrease in apical Maackia amurensis agglutinin binding. These results suggest that South Asians with ulcerative colitis show a different distribution of terminal N-acetyl neuraminyl residues, either in their alpha-2,6 or alpha-2,3 linkage, compared with their European counterparts. The changes in sialylation observed in European cases compared with normal disease-free control subjects were present in quiescent disease, but were also related to disease activity. Their absence in Asians with ulcerative colitis may imply an inherent, genetically determined variation in this group, which may also play a part in their reduced risk of subsequent malignancy.

The effect of variations in PO2 and agitation rate on byssogenesis, motility, and survival of the zebra mussel (Driessena polymorpha) was investigated. Mussels exposed to a PO2 {le} 15.4 torr exhibited increased mortality, reduced motility, and significant suppression of byssogenesis. At 7.7 and 15.4 torr, mean survival times were 5.2 and 5.8 days, maximum survival times being 15 and 16 days, respectively. After 21 days at a PO2 of 23.1 torr, sample mortality was 33.3% and declined to 18.2% at 30.9 torr. There was no mortality at full air O2 saturation (~ 154.3 torr). Adult zebra mussels exhibited the highest rate of byssogenesis in still water (0 cycles per minute [CPM]). Rate of byssogenesis progressively decreased as agitation rate increased. At 30 and 40 CPM, rate of byssal thread production was significantly lower than at 0 CPM. After 21 days, means of 58.6 and 44.8 byssal threads/mussel were found in the byssal mass of specimens exposed to 30 and 40 CPM, respectively, significantly fewer than the mean of 92.7 threads/mussel recorded in still water. Suppression of byssogenesis in D. polymorpha under hypoxic conditions is a response similar to that reported for the marine mytilid Mytilis edulis; however, suppression of byssogenesis with elevated agitation rate is the opposite response to that reported for M. edulis.

Giant hepatocytes are commonly found in several neonatal and infantile liver diseases, but are rarely found in adult liver disease. A 42 year old white woman presented with a five month history of paraesthesia and numbness of both the upper and lower limbs and with vague abdominal pain. Abnormal liver function was noted on routine screening. Ultrasound scan of the abdomen showed gallstones; barium enema, ERCP and computed tomography scan were all normal. IgG antibodies to double stranded DNA were present at a titre of 40 units. Anti-cardiolipin antibodies, anti-mitochondrial antibodies and rheumatoid factor were not detected. Serology for hepatitis A, B, C, and paramyxoviruses was negative, as was the Paul Bunnell test. A clinical diagnosis of systemic lupus erythematosus (SLE) with an axonal sensory polyneuropathy was made, the latter confirmed on biopsy of the sural nerve. Giant cells were noted on liver biopsy. The patient was treated with corticosteroids; liver function had improved after two years of follow up. When extensive giant cell transformation is noted on liver biopsy, particularly when neuropathy is also a feature, the possibility of an association with SLE should be considered.

A case of amyloid tumour of the colon and the first in association with a carcinoma is reported. A previously healthy 65 year old man presented with non-specific symptoms of lower abdominal pain and flatulence without rectal bleeding. A clinical diagnosis of diverticular disease was made and colonoscopy performed. Two lesions (one at 15 cm and the other at 30 cm from the anal margin) were found on endoscopy and removed. On histology, the lesion at 15 cm was a moderately differentiated adenocarcinoma and that at 30 cm contained amyloid. Further tests (standard tinctorial methods and immunohistochemistry) revealed the 30 cm lesion to be an amyloid tumour of the colon of AL (lambda) type. When biopsy of an atypical, large, solitary colorectal lesion reveals amyloid deposition, the possibility of an amyloid tumour should be considered and the lesion resected.

In the first 19 months of screening, the North Western Regional Transfusion Centre (RTC) tested 224,000 consecutive blood donors for antibody to hepatitis C virus (anti-HCV) by second generation enzyme immunoassay (EIA). Of these, 366 repeatedly reactive samples were referred for confirmatory testing at Manchester Public Health Laboratory (PHL). There, the initial EIA was repeated, together with two further EIAs. All the referred samples were subjected to a confirmatory line immunoblot (RIBA-II). Reverse transcription followed by the polymerase chain reaction (RT-PCR), in order to detect viral RNA, was performed on selected samples. Among the donors, 61 accepted offers for medical review and were assessed for risk factors, clinical findings and results of standard liver function tests. Of these donors, 53 proceeded to liver biopsy. The overall prevalence of confirmed positive donors was 0.04%. Main risk factors identified included intravenous drug abuse in 31 (51%) donors and prior blood transfusion in 12 (20%) but a risk factor was not apparent in 11 (18%). Viraemia, detected by RT-PCR, could be predicted with a high degree of accuracy by means of the readily available and simpler screening and confirmatory tests (EIA and RIBA-II). Established chronic hepatitis was demonstrated in 90% of the liver biopsies. A trend towards worsening histological findings accompanied increasing concentrations of serum transaminase. Even so, many donors with normal transaminase values had abnormal biopsies including those showing chronic active hepatitis (CAH). These findings indicate that a substantial proportion of previously unrecognised asymptomatic persons with established chronic liver disease exists among North Western blood donors.(ABSTRACT TRUNCATED AT 250 WORDS)

Objectives: To assess histopathologists' ability to accurately diagnose bronchopneumonia, both on naked eye and microscopic examination; to extrapolate from the error rate to determine whether the role of the necropsy in monitoring the epidemiology of clinical error might be compromised., Methods: Review of archival histological sections and necropsy reports from two teaching hospitals in Manchester. The main outcome measures identified were the proportions of macroscopic diagnoses of bronchopneumonia which were confirmed by the original pathologist on histological examination, and which could be confirmed on histological review by independent pathologists, together with the proportion of discrepant diagnoses remedied in the final report by the original pathologist., Results: Of 279 cases where a macroscopic diagnosis of bronchopneumonia had been noted in the original provisional necropsy report, the original histopathologist described bronchopneumonia in only 206 (73.8%) in the subsequent final report, which took histology into account. Bronchopneumonia could be confirmed on independent histological review in only 193 (69.2%) of these cases. The original histopathologist diagnosed 74 cases of bronchopneumonia on histological grounds only, of which only 57 (77.0%) could be confirmed on review. Of a total of 160 discrepancies between the original naked eye diagnoses and the final reviewed diagnoses, only 130 (81.3%) had been remedied by the original pathologist., Conclusions: There is a considerable discrepancy rate between naked eye diagnoses of bronchopneumonia at necropsy and diagnoses confirmed on microscopy. If this discrepancy rate is extrapolated to other common lesions, then the role of the necropsy in clinical audit may be compromised. Pathologists need to take steps to monitor and improve their own diagnostic standards.