Background Long-term side effects associated with the treatment of Hodgkin’s lymphoma (HL) have frequently been reported during the last decades. Studies have shown increased mortality in HL survivors. Following Hodgkin’s lymphoma, second malignancies (SM) and cardiovascular disease (CVD) are the most common causes of death in individuals treated for HL. This study investigates the incidence of side effects such as SM, CVD and infections in a cohort diagnosed with HL in Sweden between 1965 and 1995. In addition, this study identifies covariate risk factors for late side effects in order to develop strategies that prevent morbidity and mortality in HL survivors. Methods Using the Swedish Cancer Registry (SCR) at the National Board of Health and Welfare and the Multi-Generation Registry at Statistics (MGR) Sweden, we identified 6946 individuals diagnosed with HL between the years 1965 and 1995, and their first degree relatives (FDR) (n=17 858). In addition we identified the malignancies and inpatient care for CVD and infections for the HL cohort and their FDR. The standard incidence ratio (SIR) was calculated for the risk of SM, CVD and infections. For SM and CVD the risk also was stratified and calculated for family history of disease. The Swedish Hodgkin Intervention and Prevention study (SHIP), a prospective study, invited 702 individuals treated for HL at the age of 45 years or younger and who were treated in the region of Skåne, Uppsala or Umeå. The participants completed a questionnaire and were invited to an out-patient visit to an oncologist with clinical examination and blood tests. Any pathological findings were referred for further investigation. Results An increased risk for SM in HL long-term survivors was observed and seems to increase with the number of FDRs with cancer. There was also an increased risk for inpatient care due to congestive heart failure (CHF) and coronary artery disease (CAD). A family history of CHF and CAD further increased the risk for these diseases. The risk for inpatient care due to infections was increased and remained increased after 20 years or longer. The risk for infections was associated with splenectomy and hypothyroidism. Radiotherapy was an independent risk factor for cardiovascular disease in the cohort of the prospective study. ConclusionLong-term survivors from HL have an increased risk for developing late side effects such as SM, CVD and infections. Since many HL patients are young and the cure rate from the disease is high, it is of great importance to offer focused surveillance programs to selected individuals who are at high risk, e.g. individuals who received radiotherapy as part of their treatment and who have other known risk factors for cardiovascular disease such as hypertension, hypercholesterolemia, family history and smoking.

Introduction: Although drug-related problems (DRPs) are known to be prevalent in elderly patients, there are not many studies that have been performed in geriatric outpatients at public health facilities in South Africa. Thus, the prevalence of DRPs in elderly outpatients attending Addington Hospital was investigated and suitable preventive intervention strategies to overcome or minimise these DRPs were developed. Research Methodology: The study was conducted in two phases. Phase 1 was conducted in March and April 1998, during which 281 elderly patients on chronic medical treatment were chosen for the study by systematic random sampling, according to specific inclusion criteria. Data collection was via a retrospective review of the elderly patient's medical notes and by personally interviewing the patient. Two research instruments were used in this phase. The customised Patient Profile (PF) form helped to delineate DRPs in the elderly patients. A Prescription Intervention Form (PIF) was used to inform the prescriber of the DRP and to make recommendations to change the drug therapy in order to overcome the DRP. In phase 2 of the study, intervention strategies were devised to address some of the major DRPs identified in phase 1 of the study. A patient counselling leaflet, prescribing guidelines for geriatric patients and a protocol for counselling of in-patients were developed. In addition, two DRP reporting systems were developed for surveillance of adverse drug reactions and medication errors during dispensing. Results and Discussions: Most geriatric subjects suffered from multiple, chronic conditions, these being hypertension (64.8%) followed by ischaemic heart disease (43.8%), musculoskeletal disorders (arthritis or gout) (42.7%), diabetes (29.2%), chronic obstructive airways disease (13.2%), hypercholesteremia (11.7%) and arrythmias (atrial fibrillation) (11.0%). The 281 patients were taking 1730 prescribed drugs, with a mean of 6.2 (range 3 to 15) prescribed drugs per patient. An astounding 45.6% of the total geriatric patients were taking or using between 7 to 9 medicines and 10.3% were taking or using between 10 to 15 medicines. The antihypertensives (15.9%) were the most widely prescribed drugs followed by medicines acting on CNS (10.9%), coronary vasodilators (9.1%), diuretics (9.1%) and medicines acting on the musculoskeletal system (8.7%). A total of 856 actual DRPs experienced by 262 geriatric patients (93.2%) ranged from 1 to 11 DRPs. The greater the number of prescribed drugs the greater the actual DRPs experienced by geriatric patients (p = 0.000). The most common DRPs were those involved in drug safety (56.6%); effectiveness of the drug therapy (20.8%); compliance (7.8%) and indication of drug therapy (7.6%). 159 elderly patients (56.6%) experienced 223 adverse effects either with their current or past prescribed medicines. The most common ADRs were as follows: gastro-intestinal ulceration (11.0%), cough (9.3%), diuretic side effects (dehydration, fatigue, hypotension, etc) (7.1%), constipation (6.8%), equilibrium problems (6.4%) and headaches (6.4%). For those DRPs warranting interventions, the mean number of prescription interventions in the entire sample population of 281 elderly patients was 0.65 ± 1.16. 87 elderly patients (30.1 %) had from 1 to 4 interventions on their current prescription. The most common prescription interventions were on problems involving drug therapy monitoring (26.9%), safety of drug therapy (26.5%), indication of drug therapy (17.5%), prescribing errors (15.3%) and prescription information omission (11.1 %). The three intervention strategies and DRPs surveillance reporting systems were successfully devised and developed. Conclusions: A profile related to the elderly patient's medical history and pharmacotherapy was completed for each of the 281 patients. General trends of prescribing pattern prevalence of DRPs and the prescribed inappropriate medication was established. The interventions of problem prescriptions were based on a newly developed PIF. The development and implementation of suitable intervention strategies to minimise DRPs were as follows: a compliance information leaflet, prescribing guidelines and the protocol for counselling in-patients. A medication error form as well as an adverse drug reaction reporting forms was developed for surveillance of DRPs. The recommendations for clinical practice and directions for future research that are presented should help to make drug therapy in the elderly safer and more effective. / Thesis (M.Pharm.)-University of Durban-Westville, 2000.

Atypical antipsychotics (AAPs) are associated with metabolic sequelae including risk of type 2 diabetes. Evidence points to a weight-gain independent and direct drug effect on glucose homeostasis. While the exact mechanisms remain elusive, the heterogeneous binding profiles of AAPs likely include receptors involved in glucose metabolism. We aimed to clarify weight-gain independent mechanisms of AAP-induced alterations in insulin secretion. Deconstruction of the receptor binding profiles of these agents was done using representative antagonists and the hyperglycemic clamp. We assessed the acute effects of several selective receptor antagonists on glucose metabolism, namely prazosin, idazoxan, MDL100907, SB242084 and WAY100635. Prazosin and MDL100907, selective α1 and 5HT2A antagonists, respectively, caused significant decreases in both insulin and C-peptide secretion. A decreased glucose infusion rate and disposition index was also found in the prazosin group. Antagonism of the α1 and 5HT2A receptors may be involved in AAP-induced glucose dysregulation, however, the responsible mechanisms remain unknown.

Atypical antipsychotics (AAPs) are associated with metabolic sequelae including risk of type 2 diabetes. Evidence points to a weight-gain independent and direct drug effect on glucose homeostasis. While the exact mechanisms remain elusive, the heterogeneous binding profiles of AAPs likely include receptors involved in glucose metabolism. We aimed to clarify weight-gain independent mechanisms of AAP-induced alterations in insulin secretion. Deconstruction of the receptor binding profiles of these agents was done using representative antagonists and the hyperglycemic clamp. We assessed the acute effects of several selective receptor antagonists on glucose metabolism, namely prazosin, idazoxan, MDL100907, SB242084 and WAY100635. Prazosin and MDL100907, selective α1 and 5HT2A antagonists, respectively, caused significant decreases in both insulin and C-peptide secretion. A decreased glucose infusion rate and disposition index was also found in the prazosin group. Antagonism of the α1 and 5HT2A receptors may be involved in AAP-induced glucose dysregulation, however, the responsible mechanisms remain unknown.

Background: During the past 5 decades, hormone replacement therapy (HRT) has been used, and appreciated for its beneficial effects, by millions of women in their menopause. As treatment for climacteric symptoms, estrogen is outstanding, and effects on hot flushes, vaginal dryness, and insomnia have been widely documented. The increased risks of venous thrombosis and breast cancer, however, restrict the use of estrogen. Estrogen treatment in women with a remaining uterus includes a progestin, added to protect the endometrium from hyperplasia and malignancies. The long-standing clinical impression, that progestin addition negatively influences mood, has been discussed in previous studies. Mood deterioration is, however, not mortal, although mood is important to the wellbeing and daily functioning of women treated with hormones. Studies of the mental side effects of HRT add to our understanding of steroid effects in the brain. Aims and methods: In our studies, we aimed to establish to what extent negative side effects cause women to discontinue HRT, and find out which drug compounds lead to mood deterioration. The questions asked were whether the type and dose of progestin and the estrogen dose during the progestin addition influence the mood and physical symptoms during sequential HRT. Compliance with HRT and reasons for discontinuing the therapy were evaluated in a retrospective longitudinal follow-up study. Treatment effects were studied in three randomized, double-blind, cross-over trials. During continuous estrogen treatment, effects of sequential addition of a progestin were studied by comparing two different progestins, medroxyprogesterone acetate (MPA) andnorethisterone acetate (NETA), comparing different doses of the same progestin, MPA, and comparing two doses of estrogen during addition of the same dose of MPA. The main outcome measure was the daily rating on mood and physical symptoms kept by the participants throughout the studies. The clinical trials were carried out at three gynecological centers in northern Sweden. Results and conclusions: Besides fear of cancer and a wish to determine whether climacteric symptoms had meanwhile disappeared, negative side effects was the most common reason or discontinuing HRT. Tension in the breasts, weight gain, a depressed mood, abdominal bloating, and irritability were the most important side effects seen both in women who continued HRT and in women who had discontinued the therapy. In our clinical trials, we showed that addition of a progestin to estrogen treatment induces cyclic mood swings characterized by tension, irritability, and depression, as well as increased breast tension, bloatedness, and hot flushes. Women with a history of premenstrual syndrome (PMS) appeared to be more sensitive to the progestin addition and responded with lower mood scores compared with women without previous PMS. In our studies, MPA provoked depressed mood to a lesser extent than did NETA. Surprisingly, the higher dose of MPA (20 mg) enhanced the mood, compared with 10 mg, when added to estrogen treatment. In women continuously treated with 3 mg estradiol, mood and physical symptoms worsened during the progestin addition, as compared with treatment with 2 mg estradiol. The negative side effects seen during sequential HRT have much in common with symptoms seen in the premenstrual dysphoric disorder (PMDD), which is a psychoneuroendocrine disorder with psychiatric expression. Explanations for treatment effects on mood are likely to be found in drug interactions with neurotransmitter systems of the brain. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 2003</p> / digitalisering@umu

Access to abstract restricted until 12/14/2014. / Access to thesis restricted until 12/14/2014. / Department of Biology

We did not know the patterns of using antihypertensive drugs in outpatient settings in Israel that is why we raised a research aim to analyze the pattern of use of HBP in outpoint setting. In order to meet this aim we raised several research objectives:. 1) Does lifestyle modification is important for the patient for blood pressure control? 2) Do the patients need to change their medication at set of time until BP goals reached? 3) Does the use of more than one drug would help achieving better HBP results? Does the use of single doses combination would have better affect then using fixed dose combination? 4) How often noncompliance take in HBP control? 5) How many patients suffer from side effects? Methods: a questionnaire composed of 36 questions and qualitative statistical analysis. / Mes nežinojome, kad naudojant antihipertenzinių vaistinių preparatų ir ambulatorinėmis Izraelyje, kuris yra, kodėl mes iškėlė Tyrimo tikslas išanalizuoti naudojimo HBP Išėjo taško nustatymo modelį modelius. Siekiant įgyvendinti šį tikslą, mes iškėlė kelis mokslinių tyrimų tikslams:. 1) Ar gyvenimo būdo pakeitimas yra svarbus kraujospūdžio kontrolės pacientui? 2) Ar pacientai turi pakeisti savo vaistą esant rinkinį, kol pasiekė BP tikslai? 3) Ar iš daugiau nei vieno narkotiko naudojimas padėtų pasiekti geresnių HBP rezultatus? Ar vienos dozės deriniu būtų geriau veikia tada naudojant fiksuotų dozių derinys? 4) Kaip dažnai nesilaikymo imtis HBP kontrolės? 5) Kiek pacientų kenčia nuo šalutinio poveikio? Metodai: Klausimynas sudarytas iš 36 klausimų ir kokybinio statistinę analizę.

Mucositis manifesting as diarrhoea is a common side effect of chemotherapy which remains poorly understood. It is one of a number of manifestations of alimentary mucositis, which affects the entire gastrointestinal tract. The exact number of patients that are affected by diarrhoea as a result of treatment is uncertain, although it is believed that approximately 10% of patients with advanced cancer will be afflicted. Despite advances in the understanding of oral and small intestinal mucositis over recent years, large intestinal mucositis, including diarrhoea, has not been well defined and the underlying mechanisms of the condition are yet to be established. The majority of the literature available concerning diarrhoea is based on clinical observations, with very little basic research existing. However, from the research conducted, it is likely that the intestinal microflora and mucins play a role in the development of chemotherapy-induced diarrhoea. This thesis will examine in detail what is known about the mechanisms of chemotherapy-induced diarrhoea (CID). Furthermore it will explore the potentially important relationship between intestinal microflora, the luminal environment and the subsequent development of chemotherapy-induced mucositis and diarrhoea. 5-Fluorouracil (5-FU) is a commonly used chemotherapy agent in clinical oncology practice. Two of its major side effects are mucositis and diarrhoea. The structure of mucins offers mucosal protection, and allows maintenance of intestinal flora by providing attachment sites and preventing bacterial overgrowth and/or penetration. Following treatment with 5-FU, we showed decreases in Clostridium spp., Lactobacillus spp. and Streptococcus spp., and an increase in Escherichia spp. in the jejunum. In the colon, 5-FU caused decreases in Enterococcus spp., Lactobacillus spp. and Streptococcus spp. Real time PCR of faecal samples showed decreasing trends in Lactobacillus spp. and Bacteroides spp., and an increasing trend in E. coli. Significant increases (p<0.05) were seen in Clostridium spp. and Staphylococcus spp. at 24 h. Goblet cell numbers decreased significantly in the jejunum from 24-72 h, with a significant increase in the percentage of cavitated goblet cells, suggesting 5-FU treatment causes significant changes in intestinal flora and mucin secretion in rats. These changes could result in systemic effects, and in particular may contribute to the development of chemotherapy-induced mucositis. Irinotecan causes cholinergic and delayed onset diarrhoea in patients, in which β-glucuronidase produced by gut bacteria is thought to be involved. Diarrhoea was observed in treated rats, as expected, following irinotecan treatment. β-glucuronidase expression increased in the jejunum and colon. Faecal flora changed quantitatively after treatment also, with increases in E. coli, Staphylococcus spp., and Clostridium spp. (all β-glucuronidase producing), and decreases in Lactobacillus spp., Bifidobacterium spp. (both beneficial bacteria), and Bacteroides spp. (β-glucuronidase producing, major component of intestinal flora), suggesting that irinotecan-induced diarrhoea may be caused by an increase in β-glucuronidase producing bacteria. However, the increase in bacteria may also be caused by irinotecan, further exaggerating the toxicity of the drug, and emphasising the need for these specific bacteria to be therapeutically targeted for successful treatment regimens to be accomplished. Mucus production appears to be increased after irinotecan treatment, which may contribute to the development of diarrhoea. Goblet cells were demonstrated to decrease significantly after irinotecan treatment. However, mucin secretion increased. Mucin expression changed significantly after treatment. Muc2 and Muc4 decreased significantly in the villi of the jejunum after treatment, Muc2 and Muc4 decreased significantly in the crypts. Muc2 decreased significantly in the colon. This indicates that irinotecan causes an increase in mucin secretion and a net decrease in mucin-producing goblet cells, and the expression of Muc2 and Muc4 in the gastrointestinal tract is altered following treatment. Increased mucin secretion is likely to be related to altered mucin expression, and may contribute to chemotherapy-induced diarrhoea. To determine if the changes to the intestinal microflora caused by chemotherapy could be translated to the clinic, a pilot clinical study was carried out. Sixteen patients experiencing CID were recruited to the study with two control subjects. A large proportion of patients (75%) demonstrated a reduced anaerobic component of their faecal microflora. A reduced diversity of species was also observed in patients. The majority of patients exhibited decreases in Clostridium spp., Lactobacillus spp. and Bifidobacterium spp., whilst all patients exhibited decreases in Bacteroides spp. and Enterococcus spp. Patients receiving antibiotics did not exhibit any marked differences to patients not receiving antibiotics. This indicates that the results observed in the animal studies are clinically relevant, and further research into this area should be undertaken. CID is associated with marked changes in the intestinal microflora. These changes may result in diminished bacterial functions within the gut, altering gut function and initiating intestinal damage, resulting in the onset of diarrhoea. In conclusion, there is clear evidence demonstrating chemotherapy treatment results in changes to the intestinal microflora and mucin secretion, which may be responsible in part for the development of severe mucositis and diarrhoea. Irinotecan toxicity may be compounded by the increase in β-glucuronidase producing bacteria. The intestinal flora of cancer patients experiencing CID is also noticeably different to that of healthy subjects. Irinotecan causes changes to mucin secretion, and the specific expression of Muc2, Muc4 and Klf4, suggesting that secretory control by the enteric nervous system may also be affected by chemotherapy. This research has extended the understanding of chemotherapy-induced mucositis and diarrhoea, complex side effects of chemotherapy. However, new areas for future research have also been identified. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1352119 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, 2009

Injury and illness associated with drugs are major problems in Australia and around the world, despite significant developments in the area of adverse drug reaction (ADR) decision support technology. The aims of this thesis are: to investigate the ADR decision domain; to determine factors that may assist in the prevention, detection and management of ADRs; and, to inform the pre-requirements analysis phase of the development of decision support systems. An approach has been taken that permits open and grounded study of the decision environment. This approach can then be used to frame and inform the design of an ADR decision support system. Fifteen case studies that comprise self selected consumers, the treating medical practitioner/s and expert perspectives of a single instance of an ADR (fifteen in-depth consumer interviews, eight in-depth medical practitioner interviews and 30 expert written questionnaires), have been collected and analysed using a grounded theory approach, a symbolic interactionist theoretical framework and a social constructionist epistemology. The analysis was performed from three perspectives: individual case study analysis (all interviews for an instance of an ADR); group analysis (consumer, medical practitioner and expert views) and analysis combining the individual case studies and groups of data. Concepts, themes and theory have emerged from these data in the following areas: • the contribution of the differences in understanding of the core concepts within this domain, to misunderstandings between decision-makers; • the consumer as a diagnostic decision-maker in the ADR decision domain; • differential diagnostic strategies used by the consumers and medical practitioners; • complexities in the ADR decision domain that make diagnosis difficult; • the role of ADR information in consumer and medical practitioner decision-making; • decision types used by consumers and medical practitioners in the ADR decision domain; • resources used by consumers, medical practitioners and experts to inform their ADR decisions; • decision-making with partial knowledge of the consumer case history, drug behaviour and diseases; • the impact of suspected ADRs on consumers and on future decision-making; • medical practitioner/consumer decision-making models; and, • reasons for low ADR reporting and the impact on the development of new ADR knowledge. The results above suggest the following: • The ADR decision domain is more complex than the current ADR decision support focus and that broadening this focus may assist in providing a more complete and useful decision support solution. • Improving the prevention, detection and management of ADRs requires more than providing prescribers with up to date ADR information. Other important factors are sharing of information, awareness of the role of the consumer, a collaborative approach between the consumers and medical practitioners, and generation of new ADR knowledge. • A grounded theory analysis of case study data using the theoretical perspectives of social constructionism and symbolic interactionism provided insight into this domain from the perspectives of multiple decision-makers. This may be an approach that can be used by systems analysts to inform the requirements analysis phases of decision support within other domains. The results of this qualitative work are preliminary. Future work is required to confirm and expand these results. / Doctor of Philosophy

Mucositis manifesting as diarrhoea is a common side effect of chemotherapy which remains poorly understood. It is one of a number of manifestations of alimentary mucositis, which affects the entire gastrointestinal tract. The exact number of patients that are affected by diarrhoea as a result of treatment is uncertain, although it is believed that approximately 10% of patients with advanced cancer will be afflicted. Despite advances in the understanding of oral and small intestinal mucositis over recent years, large intestinal mucositis, including diarrhoea, has not been well defined and the underlying mechanisms of the condition are yet to be established. The majority of the literature available concerning diarrhoea is based on clinical observations, with very little basic research existing. However, from the research conducted, it is likely that the intestinal microflora and mucins play a role in the development of chemotherapy-induced diarrhoea. This thesis will examine in detail what is known about the mechanisms of chemotherapy-induced diarrhoea (CID). Furthermore it will explore the potentially important relationship between intestinal microflora, the luminal environment and the subsequent development of chemotherapy-induced mucositis and diarrhoea. 5-Fluorouracil (5-FU) is a commonly used chemotherapy agent in clinical oncology practice. Two of its major side effects are mucositis and diarrhoea. The structure of mucins offers mucosal protection, and allows maintenance of intestinal flora by providing attachment sites and preventing bacterial overgrowth and/or penetration. Following treatment with 5-FU, we showed decreases in Clostridium spp., Lactobacillus spp. and Streptococcus spp., and an increase in Escherichia spp. in the jejunum. In the colon, 5-FU caused decreases in Enterococcus spp., Lactobacillus spp. and Streptococcus spp. Real time PCR of faecal samples showed decreasing trends in Lactobacillus spp. and Bacteroides spp., and an increasing trend in E. coli. Significant increases (p<0.05) were seen in Clostridium spp. and Staphylococcus spp. at 24 h. Goblet cell numbers decreased significantly in the jejunum from 24-72 h, with a significant increase in the percentage of cavitated goblet cells, suggesting 5-FU treatment causes significant changes in intestinal flora and mucin secretion in rats. These changes could result in systemic effects, and in particular may contribute to the development of chemotherapy-induced mucositis. Irinotecan causes cholinergic and delayed onset diarrhoea in patients, in which β-glucuronidase produced by gut bacteria is thought to be involved. Diarrhoea was observed in treated rats, as expected, following irinotecan treatment. β-glucuronidase expression increased in the jejunum and colon. Faecal flora changed quantitatively after treatment also, with increases in E. coli, Staphylococcus spp., and Clostridium spp. (all β-glucuronidase producing), and decreases in Lactobacillus spp., Bifidobacterium spp. (both beneficial bacteria), and Bacteroides spp. (β-glucuronidase producing, major component of intestinal flora), suggesting that irinotecan-induced diarrhoea may be caused by an increase in β-glucuronidase producing bacteria. However, the increase in bacteria may also be caused by irinotecan, further exaggerating the toxicity of the drug, and emphasising the need for these specific bacteria to be therapeutically targeted for successful treatment regimens to be accomplished. Mucus production appears to be increased after irinotecan treatment, which may contribute to the development of diarrhoea. Goblet cells were demonstrated to decrease significantly after irinotecan treatment. However, mucin secretion increased. Mucin expression changed significantly after treatment. Muc2 and Muc4 decreased significantly in the villi of the jejunum after treatment, Muc2 and Muc4 decreased significantly in the crypts. Muc2 decreased significantly in the colon. This indicates that irinotecan causes an increase in mucin secretion and a net decrease in mucin-producing goblet cells, and the expression of Muc2 and Muc4 in the gastrointestinal tract is altered following treatment. Increased mucin secretion is likely to be related to altered mucin expression, and may contribute to chemotherapy-induced diarrhoea. To determine if the changes to the intestinal microflora caused by chemotherapy could be translated to the clinic, a pilot clinical study was carried out. Sixteen patients experiencing CID were recruited to the study with two control subjects. A large proportion of patients (75%) demonstrated a reduced anaerobic component of their faecal microflora. A reduced diversity of species was also observed in patients. The majority of patients exhibited decreases in Clostridium spp., Lactobacillus spp. and Bifidobacterium spp., whilst all patients exhibited decreases in Bacteroides spp. and Enterococcus spp. Patients receiving antibiotics did not exhibit any marked differences to patients not receiving antibiotics. This indicates that the results observed in the animal studies are clinically relevant, and further research into this area should be undertaken. CID is associated with marked changes in the intestinal microflora. These changes may result in diminished bacterial functions within the gut, altering gut function and initiating intestinal damage, resulting in the onset of diarrhoea. In conclusion, there is clear evidence demonstrating chemotherapy treatment results in changes to the intestinal microflora and mucin secretion, which may be responsible in part for the development of severe mucositis and diarrhoea. Irinotecan toxicity may be compounded by the increase in β-glucuronidase producing bacteria. The intestinal flora of cancer patients experiencing CID is also noticeably different to that of healthy subjects. Irinotecan causes changes to mucin secretion, and the specific expression of Muc2, Muc4 and Klf4, suggesting that secretory control by the enteric nervous system may also be affected by chemotherapy. This research has extended the understanding of chemotherapy-induced mucositis and diarrhoea, complex side effects of chemotherapy. However, new areas for future research have also been identified. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1352119 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, 2009