Gastrointestinal complications after kidney transplantation

The aim of the study was to evaluate gastrointestinal (GI) complications after kidney transplantation in the Finnish population. The adult patients included underwent kidney transplantation at Helsinki University Central Hospital in 1990-2000. Data on GI complications were collected from the Finnish Kidney Transplantation Registry, patient records and from questionnaires sent to patients. Helicobacter pylori IgG and IgA antibodies were measured from 500 patients before kidney transplantation and after a median 6.8-year follow up. Oesophagogastroduodenoscopy with biopsies was performed on 46 kidney transplantation patients suffering from gastroduodenal symptoms and 43 dyspeptic controls for studies of gastroduodenal cytomegalovirus (CMV) infection. Gallbladder ultrasound was performed on 304 patients after a median of 7.4 years post transplantation. Data from these 304 patients were also collected on serum lipids, body mass index and the use of statin medication. Severe GI complications occurred in 147 (10%) of 1515 kidney transplantations, 6% of them fatal after a median of 0.93 years. 51% of the complications occurred during the first post transplantation year, with highest incidence in gastroduodenal ulcers and complications of the colon. Patients with GI complications were older and had more delayed graft function and patients with polycystic kidney disease had more GI complications than the other patients. H.pylori seropositivity rate was 31% and this had no influence on graft or patient survival. 29% of the H.pylori seropositive patients seroreverted without eradication therapy. 74% of kidney transplantation patients had CMV specific matrix protein pp65 or delayed early protein p52 positive findings in the gastroduodenal mucosa, and 53% of the pp65 or p52 positive patients had gastroduodenal erosions without H.pylori findings. After the transplantation 165 (11%) patients developed gallstones. A biliary complication including 1 fatal cholecystitis developed in 15% of the patients with gallstones. 13 (0.9%) patients had pancreatitis. Colon perforations, 31% of them fatal, occurred in 16 (1%) patients. 13 (0.9%) developed a GI malignancy during the follow up. 2 H.pylori seropositive patients developed gastroduodenal malignancies during the follow up. In conclusion, severe GI complications usually occur early after kidney transplantation. Colon perforations are especially serious in kidney transplantation patients and colon diverticulosis and gallstones should be screened and treated before transplantation. When found, H.pylori infection should also be treated in these patients.

Cow’s milk related gastrointestinal symptoms in adults

The purpose of this study was to evaluate subjective food-related gastrointestinal symptoms and their relation to cow’s milk by determining the genotype of adult-type hypolactasia, measuring antibodies against milk protein, and screening the most common cause for secondary hypolactasia, namely coeliac disease. The whole study group comprised 1900 adults who gave a blood sample for the study when they attended a health care centre laboratory for various reasons. Of these 1885 (99%) completed a questionnaire on food-related gastrointestinal symptoms. Study No. I evaluated the prevalence of adult-type hypolactasia and its correlation to self-reported milk induced gastrointestinal symptoms. The testing for hypolactasia was done by determination of the C/T-13910 genotypes of the study subjects. The results show that patients with the C/C-13910 genotype associated with adult type hypolactasia consume less milk than those with C/T-13910 and T/T-13910 genotypes. Study No. II evaluated the prevalence and clinical characteristics of undiagnosed coeliac disease in the whole study population with transglutaminase and endomysium antibodies and their correlation with gastrointestinal symptoms. The prevalence of coeliac disease was 2 %, which is surprisingly high. Serum transglutaminase and endomysium antibodies are valuable tools for recognising an undiagnosed coeliac disease in outpatient clinics. In the study No. III the evaluation of milk protein IgE related hypersensitivity was carried out by stratifying all 756 study subjects with milk related problems and randomly choosing 100 age and sex matched controls with no such symptoms from the rest of the original study group. In the study No. IV 400 serum samples were randomly selected for analyzing milk protein related IgA and IgG antibodies and their correlation to milk related GI-symptoms. The measurement of milk protein IgA, IgE or IgG (studies No. III and IV) did not correlate clearly to milk induced symptoms and gave no clinically significant information; hence their measurement is not encouraged in outpatient clinics. In conclusion, adult type hypolactasia is often considered the reason for gastrointestinal symptoms in adults and determination of the C/T-13910 genotypes is a practical way of diagnosing adult type hypolactasia in an outpatient setting. Undiagnosed coeliac disease, should be actively screened and diagnosed in order to apply a gluten free diet and avoid the GI-symptoms and nutritional deficiencies. Cow’s milk hypersensitivity in the adult population is difficult to diagnose since the mechanism in which it is mediated is still unclear. Measuring of cow’s milk protein specific antibodies IgE, IgA or IgG do not correlate with subjective milk-related GI-symptoms.

Lower Gastrointestinal Microbiota in Health and Irritable Bowel Syndrome : Characterisation and Effect of Probiotic Intervention

The human gastrointestinal (GI) microbiota is a complex ecosystem that lives in symbiosis with its host. The growing awareness of the importance of the microbiota to the host as well as the development of culture-free laboratory techniques and computational methods has enormously expanded our knowledge of this microbial community. Irritable bowel syndrome (IBS) is a common functional bowel disorder affecting up to a fifth of the Western population. To date, IBS diagnosis has been based on GI symptoms and the exclusion of organic diseases. The GI microbiota has been found to be altered in this syndrome and probiotics can alleviate the symptoms, although clear links between the symptoms and the microbiota have not been demonstrated. The aim of the present work was to characterise IBS related alterations in the intestinal microbiota, their relation to IBS symptoms and their responsiveness to probiotic theraphy. In this thesis research, the healthy human microbiota was characterised by cloning and sequencing 16S rRNA genes from a faecal microbial community DNA pool that was first profiled and fractionated according to its guanine and cytosine content (%G+C). The most noticeable finding was that the high G+C Gram-positive bacteria (the phylum Actinobacteria) were more abundant compared to a corresponding library constructed from the unfractionated DNA pool sample. Previous molecular analyses of the gut microbiota have also shown comparatively low amounts of high G+C bacteria. Furthermore, the %G+C profiling approach was applied to a sample constructed of faecal DNA from diarrhea-predominant IBS (IBS-D) subjects. The phylogenetic microbial community comparison performed for healthy and IBS-D sequence libraries revealed that the IBS-D sample was rich in representatives of the phyla Firmicutes and Proteobacteria whereas Actinobacteria and Bacteroidetes were abundant in the healthy subjects. The family Lachnospiraceae within the Firmicutes was especially prevalent in the IBS-D sample. Moreover, associations of the GI microbiota with intestinal symptoms and the quality of life (QOL) were investigated, as well as the effect of probiotics on these factors. The microbial targets that were analysed with the quantitative real-time polymerase chain reaction (qPCR) in this study were phylotypes (species definition according to 16S rRNA gene sequence similarity) previously associated with either health or IBS. With a set of samples, the presence or abundance of a phylotype that had 94% 16S rRNA gene sequence similarity to Ruminococcus torques (R. torques 94%) was shown to be associated with the severity of IBS symptoms. The qPCR analyses for selected phylotypes were also applied to samples from a six-month probiotic intervention with a mixture of Lactobacillus rhamnosus GG, L. rhamnosus Lc705, Propionibacterium freudenreichii ssp. shermanii JS and Bifidobacterium breve Bb99. The intervention had been previously reported to alleviate IBS symptoms, but no associations with the analysed microbiota representatives were shown. However, with the phylotype-specific assays applied here, the abundance of the R. torques 94% -phylotype was shown to be lowered in the probiotic-receiving group during the probiotic supplementation, whereas a Clostridium thermosuccinogenes 85% phylotype, previously associated with a healthy microbiota, was found to be increased compared to the placebo group. To conclude, with the combination of methods applied, higher abundance of Actinobacteria was detected in the healthy gut than found in previous studies, and significant phylum-level microbiota alterations could be shown in IBS-D. Thus, the results of this study provide a detailed overview of the human GI microbiota in healthy subjects and in subjects with IBS. Furthermore, the IBS symptoms were linked to a particular clostridial phylotype, and probiotic supplementation was demonstrated to alter the GI microbiota towards a healthier state with regard to this and an additional bacterial phylotype. For the first time, distinct phylotype-level alterations in the microbiota were linked to IBS symptoms and shown to respond to probiotic therapy.

Collision tumour involving a rectal gastrointestinal stromal tumour with invasion of the prostate and a prostatic adenocarcinoma

Background: Gastrointestinal stromal tumours (GISTs) are the most common primary mesenchymal neoplasia in the gastrointestinal tract, although they represent only a small fraction of total gastrointestinal malignancies in adults (<2%). GISTs can be located at any level of the gastrointestinal tract; the stomach is the most common location (60-70%), in contrast to the rectum, which is most rare (4%). When a GIST invades into the adjacent prostate tissue, it can simulate prostate cancer. In this study, we report on a case comprising the unexpected collision between a rectal GIST tumour and a prostatic adenocarcinoma. Findings: We describe the complexity of the clinical, endoscopic and radiological diagnosis, of the differential diagnosis based on tumour biopsy, and of the role of neoadjuvant therapy using imatinib prior to surgical treatment. Conclusions: Although isolated cases of coexisting GISTs and prostatic adenocarcinomas have reviously been described, this is the first reported case in the medical literature of a collision tumour involving a rectal GIST and prostatic adenocarcinoma components.

Ciguatera Fish Poisoning: treatment, prevention and management

Ciguatera Fish Poisoning (CFP) is the most frequently reported seafood-toxin illness in the world, and it causes substantial physical and functional impact. It produces a myriad of gastrointestinal, neurologic and/or cardiovascular symptoms which last days to weeks, or even months. Although there are reports of symptom amelioration with some interventions (e.g. IV mannitol), the appropriate treatment for CFP remains unclear to many physicians. We review the literature on the treatments for CFP, including randomized controlled studies and anecdotal reports. The article is intended to clarify treatment options, and provide information about management and prevention of CFP, for emergency room physicians, poison control information providers, other health care providers, and patients.

Scientific assessment of marine harmful algal blooms

Algae are the most abundant photosynthetic organisms in marine ecosystems and are essential components of marine food webs. Harmful algal bloom or “HAB” species are a small subset of algal species that negatively impact humans or the environment. HABs can pose health hazards for humans or animals through the production of toxins or bioactive compounds. They also can cause deterioration of water quality through the buildup of high biomass, which degrades aesthetic, ecological, and recreational values. Humans and animals can be exposed to marine algal toxins through their food, the water in which they swim, or sea spray. Symptoms from toxin exposure range from neurological impairment to gastrointestinal upset to respiratory irritation, in some cases resulting in severe illness and even death. HABs can also result in lost revenue for coastal economies dependent on seafood harvest or tourism, disruption of subsistence activities, loss of community identity tied to coastal resource use, and disruption of social and cultural practices. Although economic impact assessments to date have been limited in scope, it has been estimated that the economic effects of marine HABs in U.S. communities amount to at least $82 million per year including lost income for fisheries, lost recreational opportunities, decreased business in tourism industries, public health costs of illness, and expenses for monitoring and management. As reviewed in the report, Harmful Algal Research and Response: A Human Dimensions Strategy1, the sociocultural impacts of HABs may be significant, but remain mostly undocumented.

The nature of the aerobic gastrointestinal bacteria of cichlid fish Sarotherodon mossambicus (Peters) and Tilapia nilotica (Linnaeus) grown under captivity

Bacteriological examination of the gastrointestinal microflora of 2 freshwater cichlid fish species (Sarotherodon mossambicus and Tilapia nilotica ) was performed, resulting in the bacteria enumeration of total viable counts of 1.06x10⁷/g and 7.75x10⁷/g of gastro-bacteria intestinal tract plus contents (wet weight) respectively, by aerobic incubation at 30+1°C. The majority (78%) of the total gut isolates from both fish species was Gram positive mesophilic which is characteristic of the higher ambient temperature in the tropics. These isolates were fastidious in their nutritional requirements and together with the rest are isogenous to bacteria autochthonous to soil and water. The occurrence of such organisms is attributed to the feeding habits of these fish. The gastrointestinal bacteria isolated in this study are transient residents but not "indigenous" in these cichlid fish.

SECRETORY MONOCLONAL IGA ANTIBODY TO HUMAN SPERM PRODUCED BY GASTROINTESTINAL IMMUNIZATION INHIBITS HUMAN SPERM ACTIVITY AND MOUSE INVITRO FERTILIZATION

BALB/c mice were immunized intragastrically with human sperm. Cells from the Peyer's patches and spleens of the immunized mice were for the preparation of hybridomas secreting antisperm monoclonal IgA (mcIgA). The specific ratio of IgA-secreting cells in Peyer's patches was much higher than that in spleen. The binding site on human sperm of 9 of 19 mcIgA was in the post-acrosomal region using an immunofluorescent assay. Two of eight selected mcIgA caused strong human sperm agglutination and three of them produced significant inhibition of mouse in vitro fertilization. No mcIgA tested caused obvious human sperm immobilization or inhibited mouse in vivo fertilization. In vitro assembly of selected mcIgA in ascites with mouse secretory component (SC) caused no significant changes in effects on sperm function and in vitro fertilization. By use of Western blotting, dimer or higher polymers were demonstrated in all selected mcIgAs and corresponding protein antigens in 6 of 8 selected mcIgAs. These results suggest that human sperm function may be inhibited and fertilization rate reduced by specific secretory IgA to human sperm and that secretory immunity to protein antigens of human sperm could be induced by intragastrointestinal immunization.

Communities of gastrointestinal helminths of fish in historically connected habitats: habitat fragmentation effect in a carnivorous catfish Pelteobagrus fulvidraco from seven lakes in flood plain of the Yangtze River, China

Background: Habitat fragmentation may result in the reduction of diversity of parasite communities by affecting population size and dispersal pattern of species. In the flood plain of the Yangtze River in China, many lakes, which were once connected with the river, have become isolated since the 1950s from the river by the construction of dams and sluices, with many larger lakes subdivided into smaller ones by road embankments. These artificial barriers have inevitably obstructed the migration of fish between the river and lakes and also among lakes. In this study, the gastrointestinal helminth communities were investigated in a carnivorous fish, the yellowhead catfish Pelteobagrus fulvidraco, from two connected and five isolated lakes in the flood plain in order to detect the effect of lake fragmentation on the parasite communities. Results: A total of 11 species of helminths were recorded in the stomach and intestine of P. fulvidraco from seven lakes, including two lakes connected with the Yangtze River, i.e. Poyang and Dongting lakes, and five isolated lakes, i.e. Honghu, Liangzi, Tangxun, Niushan and Baoan lakes. Mean helminth individuals and diversity of helminth communities in Honghu and Dongting lakes was lower than in the other five lakes. The nematode Procamallanus fulvidraconis was the dominant species of communities in all the seven lakes. No significant difference in the Shannon-Wiener index was detected between connected lakes (0.48) and isolated lakes (0.50). The similarity of helminth communities between Niushan and Baoan lakes was the highest (0.6708), and the lowest was between Tangxun and Dongting lakes (0.1807). The similarity was low between Dongting and the other lakes, and the similarity decreased with the geographic distance among these lakes. The helminth community in one connected lake, Poyang Lake was clustered with isolated lakes, but the community in Dongting Lake was separated in the tree. Conclusion: The similarity in the helminth communities of this fish in the flood-plain lakes may be attributed to the historical connection of these habitats and to the completion of the life-cycles of this fish as well as the helminth species within the investigated habitats. The diversity and the digenean majority in the helminth communities can be related to the diet of this fish, and to the lacustrine and macrophytic characters of the habitats. The lake isolation from the river had little detectable effect on the helminth communities of the catfish in flood-plain lakes of the Yangtze River. The low similarities in helminth communities between the Dongting Lake and others may just be a reflection of its unique water environment and anthropogenic alterations or fragmentation in this lake.

Effect of graded levels of rapeseed oil in isonitrogenous diets on the development of the gastrointestinal tract, and utilisation of protein, fat and energy in broiler chickens

The effect of feeding 0, 4, 8 and 16% rapeseed oil from 12-42 days of age was studied in broiler chickens on performance, digestibility of nutrients, and development of gastrointestinal tract, protein and energy metabolism. Thirty six female chickens (Ross 208) with initial body weight average 246 g were allocated to the four groups and kept pair-wise in metabolism cages. The chickens were fed similar amounts of metabolisable energy (ME) per day and similar amounts of essential amino acids relative to ME by adjusting with crystalline amino acids. The chickens were subjected to four balance periods each of five days with two 24 h measurements of gas exchange in two open-air-circuit respiration chambers inserted on the second and third day of each period. The addition of rapeseed oil increased the amount of gutfill indicating a reduced rate of passage and causing a hypertrophy of the gastrointestinal tract. There was a positive effect on feed utilisation as well as on digestibility especially of dietary fat together with higher utilisation of protein with addition of rapeseed oil. The partial fat digestibility of rapeseed oil estimated by regression was 91.1% and the partial metabolisability (ME/GE) of the rapeseed oil was estimated to 85% yielding an apparent metabolisable energy value of 34.30 MJ/kg.

Illness and elevated Human Mortality in Europe Coincident with the Laki Fissure eruption

Grattan, J. Durand, M. Taylor, S., Illness and elevated Human Mortality in Europe Coincident with the Laki fissure eruption. In: 'Volcanic Degassing: Geological Society, Special Publication 213', Oppenheimer, C., Pyle, D.M. and Barclay, J. (eds). Geological Society, London, Special Publications, 410-414, 2003.

Identification of novel innate immune mechanisms regulating inflammation in the gastrointestinal tract

The Gastro-Intestinal (GI) tract is a unique region in the body. Our innate immune system retains a fine homeostatic balance between avoiding inappropriate inflammatory responses against the myriad commensal microbes residing in the gut while also remaining active enough to prevent invasive pathogenic attack. The intestinal epithelium represents the frontline of this interface. It has long been known to act as a physical barrier preventing the lumenal bacteria of the gastro-intestinal tract from activating an inflammatory immune response in the immune cells of the underlying mucosa. However, in recent years, an appreciation has grown surrounding the role played by the intestinal epithelium in regulating innate immune responses, both in the prevention of infection and in maintaining a homeostatic environment through modulation of innate immune signalling systems. The aim of this thesis was to identify novel innate immune mechanisms regulating inflammation in the GI tract. To achieve this aim, we chose several aspects of regulatory mechanisms utilised in this region by the innate immune system. We identified several commensal strains of bacteria expressing proteins containing signalling domains used by Pattern Recognition Receptors (PRRs) of the innate immune system. Three such bacterial proteins were studied for their potentially subversive roles in host innate immune signalling as a means of regulating homeostasis in the GI tract. We also examined differential responses to PRR activation depending on their sub-cellular localisation. This was investigated based on reports that apical Toll-Like Receptor (TLR) 9 activation resulted in abrogation of inflammatory responses mediated by other TLRs in Intestinal Epithelial Cells (IECs) such as basolateral TLR4 activation. Using the well-studied invasive intra-cellular pathogen Listeria monocytogenes as a model for infection, we also used a PRR siRNA library screening technique to identify novel PRRs used by IECs in both inhibition and activation of inflammatory responses. Many of the PRRs identified in this screen were previously believed not to be expressed in IECs. Furthermore, the same study has led to the identification of the previously uncharacterised TLR10 as a functional inflammatory receptor of IECs. Further analysis revealed a similar role in macrophages where it was shown to respond to intracellular and motile pathogens such as Gram-positive L.monocytogenes and Gram negative Salmonella typhimurium. TLR10 expression in IECs was predominantly intracellular. This is likely in order to avoid inappropriate inflammatory activation through the recognition of commensal microbial antigens on the apical cell surface of IECs. Moreover, these results have revealed a more complex network of innate immune signalling mechanisms involved in both activating and inhibiting inflammatory responses in IECs than was previously believed. This contribution to our understanding of innate immune regulation in this region has several direct and indirect benefits. The identification of several novel PRRs involved in activating and inhibiting inflammation in the GI tract may be used as novel therapeutic targets in the treatment of disease; both for inducing tolerance and reducing inflammation, or indeed, as targets for adjuvant activation in the development of oral vaccines against pathogenic attack.

Novel insights into the inflammatory basis of gastrointestinal disease

It has become clear that inflammation is beneficial to man, there are situations though that the inflammatory response causes damage to the host that is harmful to health. When the inflammatory response fails or is too strong, the health of the host is damaged and disease can occur. The implication of intestinal disease caused by an ineffective immune response is of great social and economic burden to society. The overarching purpose of this thesis is to assess inflammatory signalling targets associated with immune mediated disorders such as IBD, IBS and inflammatory liver disease. By assessing these targets and modifying their function I hope to contribute and expand further the pre-existing information on these disorders and improve the therapeutic interventions available in these debilitating conditions. I will assess the role of inflammation in disorders of the GI tract and liver IBD, IBS, hepatic inflammatory injury and furthermore, I will use pharmaceutical agents to activate and suppress components of the immune system. I will examine the inflammatory response in experimental models of disease for IBD and liver injury, I will attempt to alter these pathways using pharmaceutical intervention to delineate the disease causing mechanism that may lead to clinically relevant therapeutic interventions. In regards to IBS, I will attempt to improve the existing knowledge that exists in relation to the pathogenesis of this functional bowel disorder. I will attempt to define a mechanism by which the low grade mucosal inflammation that has been demonstrated by others arises and what this inflammation is induced by. The overall aim of this thesis is to attempt to further understand the mechanisms behind GI and liver disease. Looking at the inflammatory response in these specific conditions and how they can be altered may lead to exciting new therapies for inflammatory conditions in the gastrointestinal tract.