<b>Pressemelding:</b> Behandling av type 2 diabetes har trolig best effekt i en tidlig fase av sykdommen. Dette skriver assistentlege Elisabeth Qvigstad (36) fra Grimstad i doktoravhandlingen sin ved Norges teknisk-naturvitenskapelige universitet NTNU. Arbeidet kan bidra til at det utvikles nye medisiner mot diabetes. Avhandlingen tar utgangspunkt i type 2 diabetes, som rammer 105-120 000 nordmenn. Tidligere forskning i form av celle- og dyreforsøk har vist at vedvarende høye nivåer av fettsyrer i blodet og langvarig stimulering av insulinfrigjøring kan svekke funksjonen til de insulinproduserende beta-cellene i bukspyttkjertelen. Avhandlingen ville teste om lignende forhold er til stede hos mennesker og om korrigerende tiltak ville bedre insulinfrigjøringen ved type 2 diabetes. Nivået av frie fettsyrer hos personer med type 2 diabetes er oftest forhøyet. Langvarig faste hos friske gir også forhøyet fettsyrenivå og kan ses på som en modellsituasjon for type 2 diabetes. Qvigstad fant redusert insulinfrigjøring hos friske forsøkspersoner etter 58 timer faste. Fettsyrenivået i blod under testing ble senket ved hjelp av et nikotinsyrederivat hos friske personer og personer med type 2 diabetes. Hos friske påvirket ikke medikamentet insulinfrigjøring eller -følsomhet. Imidlertid virket behandlingen positivt på insulinfrigjøring hos de diabetikerne som hadde best blodsukker-kontroll. Derimot, når type 2 diabetikere reduserte fett i kosten, ga dette ingen utslag på insulinfrigjøringen, men noe nedsatt insulinfølsomhet. Nivået av fettvevshormoner (leptin, adiponectin) ble redusert. Den egne insulinfrigjøringen ble hemmet med medikamentet diazoxid, og insulininjeksjoner ble brukt som erstatning. Insulinfrigjøringen økte uten å endre insulinbehov eller blodsukkerkontroll sammenliknet med placebo. Disse resultatene tyder på at "betacelle-hvile" er gunstig ved type-2 diabetes. Qvigstads doktorgradsarbeid bidrar til økt forståelse av betydningen av fettsyrer for insulinfrigjøring og insulinfølsomhet hos friske og ved type 2 diabetes. I tillegg støtter funnene betydningen av "betacelle-hvile», som kan bidra til utvikling av nye medisiner mot diabetes. http://www.ntnu.no/doktorgrader/dr.med/02.03/qvigstad.htm

Diabetic nephropathy (DN) is associated with morbidity and mortality due to cardiovascular disease and renal failure. This study focused on the impact of glycemic control on the development of DN and the metabolic consequences of DN. The euglycemic hyperinsulinemic clamp technique was used to assess insulin sensitivity and insulin clearance. Two different registries, the Diabetes Incidence Study in Sweden (DISS) and the Swedish Childhood Diabetes Registry, as well as questionnaires and data from medical records were used to study diabetic complications in population-based cohorts. Microalbuminuria is an early marker of DN and may also be associated with impaired insulin sensitiv-ity in diabetic and non-diabetic subjects. We studied the relationship between insulin sensitivity and the degree of albuminuria in patients with type 1 diabetes and micro- or macroalbuminuria but normal glomerular filtration rate (GFR). We did not find a direct quantitative association between the degree of albuminuria and insulin resistance, arguing against a cause-effect relationship. With progression of DN, a decline in GFR is seen. Patients with severe renal failure have both im-paired insulin sensitivity and insulin clearance. We studied insulin sensitivity and insulin clearance in type 1 diabetes patients with three different degrees of renal involvement (none, only albuminuria, and slightly reduced GFR, ~40-70 ml/min/1.73 m2, respectively). A clear reduction in insulin sensitivity in vivo, but not in insulin clearance, was seen in the group with reduced GFR, and concomitant changes in the levels of PTH, IGF-1, IL-6 and TNF-α were found. In parallel, cellular insulin sensitivity and insulin degradation were examined in vitro, in subcutaneous fat cells but no differences were found between the three groups of patients. To study the occurrence of renal involvement in patients with modern diabetes treatment we moni-tored a cohort of young adults from the DISS-registry with onset of diabetes in 1987-88 at age 15-34 years. We found that ~7% of the patients had signs of renal involvement, i.e. incipient nephropathy (5%) and overt nephropathy (2%), after a median follow-up of ~9 years and the strongest risk markers were poor glycemic control (HbA1c) and high blood pressure. Patients with type 2 diabetes were most prone to have renal involvement in this age group. Retrospectively, we studied 94 patients diagnosed with type 1 diabetes in 1981-1992 at age 0-14 years at the Umeå University Hospital. Incipient nephropathy and background retinopathy occurred in 18 and 45%, respectively, of the patients, during ~12 years of follow-up. Glycemic control, also during the first five years of diabetes, was a strong risk marker. Young age at onset of diabetes prolonged the time to development of microvascular complications. Conclusion: Despite modern diabetes treatment some patients with diabetes develop renal involvement within the first ten years. Inadequate glycemic control, also early in the disease, is a risk marker as well as type 2 diabetes and high blood pressure. In patients with type 1 diabetes and diabetic neph-ropathy a slightly reduced GFR, but not albuminuria, is associated with insulin resistance. Concomi-tant changes in insulin-antagonistic hormones and cytokines may be involved.

The studies in the present thesis sought to define virus and host factors that can influence on the susceptibility to murine retrovirus infection. In addition, we wanted to study possible correlations between events of early infection and subsequent disease progression. For an extensive discussion of the major findings, the reader is referred to papers I-IV. The following section will give a general discussion concerning 1) some methodological aspects; 2) the course of FIS-2 infection; 3) determinants responsible for erythroleukaemia; 4) determinants responsible for immunosuppression; and, 5) does sex matter?

The purpose of the study was to: • Study the effect of vascular gas bubbles on the brain and lung • Study changes in the endothelial function caused by gas bubbles • Study the preventive effects of monoclonal anti-C5a antibody on functional changes caused by gas bubbles It is important to reveal any changes in the function of the endothelium caused by gas bubbles, as the endothelium probably plays an important role in the development of decompression sickness (DCS). Furthermore, we followed up previous studies using monoclonal anti-C5a antibody trying to prevent damages caused by gas bubbles. In order to prevent damages causes by gas bubbles and maybe prevent DCS, the mechanisms behind have to be revealed. This thesis is part of an ongoing project that for several years has tried to bring to light the “secrets” of DCS.

No description available.

The main purpose of the present work was to evaluate the efforts taken by the Norwegian surgical community in order to promote and enhance the standards of rectal cancer treatment on a national level, in particular: - to examine the outcome of rectal cancer surgery following implementation of total mesorectal excision as the standard rectal resection technique - to explore the prognostic impact of the circumferential resection margin on local recurrence, distant metastases and overall survival following mesorectal excision - to evaluate the oncological outcomes following mesorectal excision of cancer of the lower rectum, particularly the rates of local recurrence and overall survival for patients with tumours in this areas - to illustrate the influence of a rectal cancer registry as a quality control instrument on outcome of rectal treatment, and furthermore, to investigate the rates of postoperative mortality, anastomic leakage, local recurrence (LR) and overall survival related to hospital caseload among Norwegian hospitals during implementation of mesorectal excision.

The aim of this thesis is to explore why parents bring their children to homeopaths and to investigate the effect of homeopathic treatment for prevention of upper respiratory tract infections (URTI) in children. The reason for doing studies on this is that there has been a nearly threefold increase in the proportion of children among patients visiting Norwegian homeopaths. This raised the question of why it is so. Furthermore, recurrent respiratory complaints are a main reason why child patients consult homeopaths. This raised the question of the effect of homeopathic treatment in this patient group, because there is very little research on this. The thesis builds on four different studies conducted between August 2002 and June 2004. Parents of nine children that recently had been to a homeopath for the first time were interviewed to explore why parents take their children to homeopaths. All parents had been to a medical doctor before consulting the homeopath. It was the experiences with conventional medical treatment that led the parents to look for alternatives. The reasons were that 1) the parents did not want to give the medication prescribed by the doctor, 2) they wanted treatment while waiting for a problem to be assessed, 3) they did not want to continue to use the prescribed medication, 4) they stopped taking conventional medication due to side effects or 5) they were not offered any treatment by the medical doctor. The parents would consult a medical doctor if they felt insecure about the health conditions of the child and would visit a homeopath when they felt that the situation was clarified. There are parents who take their child to homeopaths despite not understanding or having belief in whether ultramolecular homeopathic medicines can have effects. One hundred and sixty-one children who had been diagnosed with an URTI by a medical doctor were recruited to participate in a trial on the effect of treatment by homeopaths for prevention of URTI in children. The children were randomly allocated to two groups. One group received an appointment immediately with one of five homeopaths who treated the patients as they do in their everyday practice. The other group (control) got such treatment after three months. The occurrence of URTI judged by the parents were significantly lower among those treated immediately by homeopaths (median 8 days in three months) compared to the control group who used self-selected conventional health care (median 13 days) (p=0.006). Homeopathic medicines are frequently used for self-treatment (over the counter-OTC). It is not known if the choice of the patient is the same, as a homeopath would have prescribed. A study was therefore conducted to explore if there can be developed indications for homeopathic medicines that facilitate that parents can chose the same medicine as a homeopath would prescribe for children with URTI. Firstly, data from a survey was used to find three medicines Calcarea carb, Pulsatilla and Sulphur that accounted for 60% of all prescription made by Norwegian homeopaths for children with URTI. Simplified constitutional indications for these medicines were developed and tested by comparing the choices of 70 parents with the prescription of eleven homeopaths. The parents were able to choose the same homeopathic medicine as homeopaths prescribed for 55% of the children. Two hundred and fifty-nine children who had been diagnosed with an URTI by a medical doctor were recruited to participate in a trial on the effect of one of three self-selected ultramolecular homeopathic medicines for prevention of URTI in children. The indications developed were used. The children was randomly allocated to receive either ultramolecular homeopathic medicine (C-30) or placebo. There was no difference in the occurrence of URTI judged by the parents among getting ultramolecular homeopathic medicine compared to those getting placebo (median 9 days in three months for both groups) (p=0.531). / Hensikten med denne avhandlingen er å undersøke hvorfor foreldre tar sine barn med til homøopat og å undersøke effekten av homøopatisk behandling i forebygging av øvre luftveisinfeksjoner (ØLI) hos barn. Bakgrunnen for de undersøkelsene som er gjort, er at det nesten er en tredobling i andelen barn blant pasienter hos homøopat. Dette utløste spørsmål om hvorfor det er slik. Videre er gjentatte luftveisplager en hovedårsak til at barn oppsøker homøopat. Fordi det er lite forskning på dette temaet ble spørsmålet om effekten av homøopatisk behandling i denne pasientgruppen også utløst. Avhandlingen bygger på fire ulike undersøkelser som er gjennomført mellom august 2002 og juni 2004. Foreldre til ni barn som nylig hadde vært hos homøopat for første gang ble intervjuet for å undersøke hvorfor foreldre tar sine barn med til homøopat. Alle foreldrene hadde vært hos lege før de kontaktet homøopaten, og det var erfaringer med legebehandlingen som fikk foreldrene til å søke alternativer. Årsakene var at foreldrene 1) ikke ønsket å gi den behandlingen lege foreskrev til barnet, 2) ønsket behandling mens barnet ventet på å bli ferdig utredet, 3) ønsket å avslutte bruken av de medisinene legen hadde foreskrevet for barnet, 4) opplevde at barnet fikk bivirkninger av behandlingen legen hadde gitt og 5) ikke ble tilbudt noen behandling hos legen. Foreldre oppsøker først lege når de er usikre eller bekymret for barnets helsetilstand. De oppsøker homøopat for behandling når dette er avklart. Det er foreldre som oppsøker homøopat med sine barn selv om de ikke forstår eller tror på effekten av homøopatiske medisiner (som kan være svært fortynnet). Ett hundre og sekstini barn som hadde vært til lege på grunn av en øvre luftveisinfeksjon ble rekruttert til å være med på en undersøkelse av effekten av behandling hos homøopat i forebyggingen av ØLI hos barn. Barna ble tilfeldig fordelt i to grupper. Barna i den ene gruppen fikk time med en gang hos en av fem homøopater som foreskrev homøopatisk behandling på vanlig måte. Den andre gruppen fikk slik behandling etter 3 måneder. Forekomsten av ØLI Hensikten med denne avhandlingen er å undersøke hvorfor foreldre tar sine barn med til homøopat og å undersøke effekten av homøopatisk behandling i forebygging av øvre luftveisinfeksjoner (ØLI) hos barn. Bakgrunnen for de undersøkelsene som er gjort, er at det nesten er en tredobling i andelen barn blant pasienter hos homøopat. Dette utløste spørsmål om hvorfor det er slik. Videre er gjentatte luftveisplager en hovedårsak til at barn oppsøker homøopat. Fordi det er lite forskning på dette temaet ble spørsmålet om effekten av homøopatisk behandling i denne pasientgruppen også utløst. Avhandlingen bygger på fire ulike undersøkelser som er gjennomført mellom august 2002 og juni 2004. Foreldre til ni barn som nylig hadde vært hos homøopat for første gang ble intervjuet for å undersøke hvorfor foreldre tar sine barn med til homøopat. Alle foreldrene hadde vært hos lege før de kontaktet homøopaten, og det var erfaringer med legebehandlingen som fikk foreldrene til å søke alternativer. Årsakene var at foreldrene 1) ikke ønsket å gi den behandlingen lege foreskrev til barnet, 2) ønsket behandling mens barnet ventet på å bli ferdig utredet, 3) ønsket å avslutte bruken av de medisinene legen hadde foreskrevet for barnet, 4) opplevde at barnet fikk bivirkninger av behandlingen legen hadde gitt og 5) ikke ble tilbudt noen behandling hos legen. Foreldre oppsøker først lege når de er usikre eller bekymret for barnets helsetilstand. De oppsøker homøopat for behandling når dette er avklart. Det er foreldre som oppsøker homøopat med sine barn selv om de ikke forstår eller tror på effekten av homøopatiske medisiner (som kan være svært fortynnet). Ett hundre og sekstini barn som hadde vært til lege på grunn av en øvre luftveisinfeksjon ble rekruttert til å være med på en undersøkelse av effekten av behandling hos homøopat i forebyggingen av ØLI hos barn. Barna ble tilfeldig fordelt i to grupper. Barna i den ene gruppen fikk time med en gang hos en av fem homøopater som foreskrev homøopatisk behandling på vanlig måte. Den andre gruppen fikk slik behandling etter 3 måneder. Forekomsten av ØLI var signifikant lavere hos de som fikk behandling hos homøopat med én gang (median 8 dager på tre måneder) sammenlignet med den andre gruppen som brukte standard behandling ved behov mens de ventet (median 13 dager) (p=0,006). Homøopatisk medisin brukes internasjonalt i stor grad til selvbehandling. Man vet ikke om pasientens eget valg av homøopatisk medisin er lik det en homøopat ville foreskrevet. Det ble derfor gjennomført en undersøkelse av om det kan utvikles beskrivelser for indikasjoner for homøopatiske medisiner som gjør at foreldre kan velge samme medisin som en homøopat foreskriver for barn med ØLI. Først ble det funnet fram til tre medisiner, Calcarea carb, Pulsatilla og Sulphur som homøopater i Norge foreskriver til 60% av barn med ØLI. Så ble det utviklet indikasjoner for disse tre medisinene som ble testet ut ved at valgene til 70 foreldre ble sammenlignet med foreskrivingen til 11 homøopater. Foreldrene valgte samme medisin som homøopaten for 55% av barna. To hundre og femtien barn som hadde vært til lege på grunn av en øvre luftveisinfeksjon ble rekruttert til å være med på en undersøkelse av effekten av en av tre selvvalgte homøopatiske medisiner i forebyggingen av ØLI hos barn. Indikasjonene som ble utviklet ble brukt. Barna ble tilfeldig fordelt til enten å få homøopatisk medisin eller placebo. Det var ingen signifikant forskjell i forekomsten av ØLI mellom de som fikk homøopatisk medisin sammenlignet med de som fikk placebo (median 9 dager på tre måneder i begge grupper) (p=0,531).

Retinoic Acid Metabolism Blocking Agents (RAMBAs) increase the endogenous levels of all-trans retinoic acid (RA) by inhibiting CYP26 enzymes. Thus they are believed to mimic the effects of retinoid treatment. Their mechanism of action and effects on vitamin A metabolism in keratinocytes are however uncertain. To explore this and the function of CYP26 in human skin was the main purpose of the project. The effects of two RAMBAs (talarozole and liarozole) on the expression of retinoid biomarkers in epidermis were studied in vivo and in vitro. Normal human skin (n=16) exposed to topical talarozole for 9 days showed similar response as previously reported for topical RA, even though no skin inflammation occurred. Lamellar ichthyosis patients (n=11) treated systemically with liarozole showed variable clinical improvement after 4 weeks with only mild effects on the retinoid biomarkers and the expression did not always correlate at the protein and mRNA levels. In these studies the proinflammatory transcripts IL-1α and TNFα were down-regulated by RAMBAs. In vitro, using an organotypic epidermis model we first studied how the RA metabolism was affected by adding RA and/or RAMBAs. We next examined the effects of the same agents on the expression of vitamin A metabolising enzymes in monolayer cultures of proliferating and differentiating keratinocytes. The results show among other things that CYP26 A1 and B1 are both involved in the catabolism of RA, and that talarozole potently increases the level of endogenous RA, primarily by inhibiting CYP26B1. However the drug´s biological effects cannot be solely attributed to increased RA levels. In conclusion, RAMBAs are promising new drugs for treatment of skin disorders, but further studies on their mechanism of action are needed.

Introduction. The outermost layer of the epidermis, the stratum corneum (SC), plays a fundamental role in our defense against microorganisms, chemicals, and dehydration. The SC is composed of tightly packed keratinized skin cells, corneocytes. For a functioning skin it is essential that corneocytes are constantly shed (desquamated). Kallikrein-related peptidase (KLK) 5 and KLK7 may be important in the desquamation process through degradation of desmosomal proteins. Severe hereditary diseases, where inhibition of KLK5 and/or KLK7 is missing, points to the importance of regulation of protease activity. KLKs may be regulated in various ways: tissue expression, activation of proforms, specific inhibitors, and physico-chemical properties like pH. Besides their involvement in desquamation, KLKs may also be important in immune defense and inflammation by processing of mediators and via activation of proteinase-activated receptors (PARs). Aims. 1. To identify and characterize previously unknown proteases in the SC. 2. To further characterize KLK5 and KLK7 with special focus on activation mechanisms. 3. To identify new inhibitors of KLKs in human SC. 4. To further characterize KLKs regarding effects of various inhibitors and substrates. 5. To study possible functions of KLKs in inflammation, in particular via activation of PAR-2. Methods. Plantar SC was used as a source for purification of proteins. Recombinant proteins were produced in different expression systems (insect cells, yeast cells, and bacteria). Different activity assays and kinetic studies were performed. Tissue expression was studied by immunohistochemistry, immunoblot and PCR. PAR-2 activation was studied by measurement of intracellular [Ca2+] and immunofluorescense in KNRK-PAR2 cells. Results. Active KLK14 was purified from extracts of plantar SC. KLK14 showed a superior catalytic efficiency as compared to KLK5 when measuring trypsin-like activity. This indicated that KLK14, despite being present in low amounts in skin, may have great relevance for skin physiology. Among enzymes tested only KLK5 showed autocatalytic activity and is so far the only enzyme found in SC that can activate proKLK7. KLK5 could also activate proKLK14. This together with studies of pH dependence on activation placed KLK5 as a possible key activating enzyme in a proposed proteolytic cascade in the SC. In plantar SC extracts we have also identified the novel Kazal-type serine protease inhibitor 9 (SPINK9). Our results indicate that SPINK9 is preferentially expressed in palmo-plantar skin and specific for KLK5. Differences found regarding substrate specificity and inhibition profile can be useful in evaluating the contribution of individual KLKs to the proteolytic activity in crude SC extracts. One interesting finding was that KLK8, present at high protein levels in the epidermis, could not be inhibited by any protease inhibitor found in the extracts. PAR-2 activation studies showed that KLK5 and 14 but neither KLK7 nor 8 can activate PAR-2. Immunohistochemistry preferentially detected KLK14 in intraepidermal parts of the sweat ducts and in dermal sweat glands but we could also show coexpression of KLK14 and PAR-2 in the SC and stratum granulosum of the epidermis in inflammatory skin disorders. To summarize, KLK involvement in desquamation may be dependent on a proteolytic activation cascade regulated by an intrinsic pH gradient and specific inhibitors present in SC. Another possible function of KLKs is as mediators of inflammation through activation of PAR-2.

<p><b>Purpose.</b> The main aim of the present study was to evaluate the effect of a low fat, low lactose diet on acute and late gastrointestinal side effects of pelvic radiotherapy. We also wanted to evaluate if such a treatment would influence the patients health related quality of life (HRQOL) in any way.</p><p><b>Background</b>. Cancer therapies and their side effects may cause nutritional problems and malnutrition. Pelvic radiotherapy, a common treatment modality for patients with carcinoma of the endometrium or cervix, is associated with both acute and late side effects that may affect nutritional status. Acute injury may lead to impaired absorption of nutrients and fluid. The patients experience diarrhoea, weight loss, nausea and vomiting. Bile salt malabsorption may be a factor in the pathogenesis of the diarrhoea. In cases of bile salt malabsorption a low fat diet will cause decreased bile salt excretion and thereby relief of symptoms. This assumption was evaluated in a small, non-randomised study in 1985. The results indicated that a low fat diet may reduce the frequency of diarrhoea and use of anti-diarrhoeal agents during radiotherapy. These findings were regarded as promising and since nutrition management guidelines for radiation enteritis were lacking in the literature, a clinical trial was planned.</p><p><b>Methods</b>. The study was designed as an open randomised clinical trial and conducted at the Norwegian Radium Hospital (NRH). The intervention diet (low fat, low lactose) was to be followed during and six weeks after radiotherapy. Measurements were performed at basement, the 3rd and last week of radiotherapy, six week after and then every 8th week. The entire period was one year. In November 1993 the surviving patients were approached again and asked to complete a questionnaire package similar to the one completed during the clinical trial. The study population was recruited from the department of gynaecology at NRH. The main selection criteria were pelvic radiotherapy (dose above 40 Gy) age = 75 years and a WHO functional status = 2. Patients were consecutive included from May 1988 through May 1990 and 143 women were included. Seventy-one were assigned to the intervention diet and 72 to the control group. In November 1993, 94 women were alive without any known relapse and 79 (84%) accepted participation. The women registered use of Loperamid and the daily number and consistency of bowel movements. The data on bowel movements was categorised and used to evaluate if diarrhoea was present or not. Nutritional status was evaluated by the means of weight development, arm muscle circumference (AMC), serum transferring (STF) and serum albumin (s-Alb). Dietary intake was assessed by 48-hour recall prior to radiotherapy, 4-days unweighed dietary record during radiotherapy and 7-days weighed dietary records during follow-up. 24-hour urinary nitrogen was used to validate the food records. HRQOL was defined as the patients' self-reported subjective physical and psychosocial situation as a consequence of disease and treatment. It was measured with the EORTC Core Quality of Life Questionnaire 36-item version (EORTC QLQ-C36).</p><p><b>Results</b>. During the last week of radiotherapy 14 patients (23%) in the intervention group and 32 (48%) in the control group reported diarrhoea (p< 0.01). The intervention group also used less anti-diarrhoea medication than the control group, 0.6 tablets per day versus 1.1 (p<0.01). Six weeks after end of radiotherapy, no group differences were found with regard to bowel movements or medication. The intervention group had a lower energy intake than the control group during radiotherapy, 5.7 MJ versus 6.5 MJ (p<0.05). The mean daily fat intake was respectively 34.3 g and 60.1 g (p<0.001). The intervention group received a significant lower part of the energy from milk products, meats, fats and sugar than the control group, and consumed more energy from vegetables and fruits, cereals and fish. Weight loss was more pronounced in the intervention group (mean reduction of 2.6 kg versus 1.7 kg) than in the control group (ns) during treatment. Mean values of AMC, s-Alb and STF were within the reference range in both groups during the entire observation period. During the last week of radiotherapy six patients (9%) in the intervention group and 4 (6%) in the control group were mildly depleted (ns). At 12 weeks and after one year none of the patients could be categorised as malnourished. No major differences in HRQOL were found between the two groups during radiotherapy and one-year follow up. Within the control group an association between diarrhoea and deteriorated role functioning, physical functioning and fatigue was found during the last week of radiotherapy that was not found in the intervention group. Regarding late effects of radiotherapy (3-4 years after radiotherapy) both groups had more diarrhoea than in the general population, 23.8 versus 9.5 (p<0.01). There was however a tendency to more pronounced diarrhoea in the control group (29.6 (SD=27.3)) than in the intervention group (19.4 (SD=25.4)) though not statistical significant. Substantial diarrhoea was associated deteriorated SF and fatigue. </p><p><b>Conclusions</b>. The intervention group had less diarrhoea and used less Loperamide during radiotherapy than the control group. This finding did not affect nutritional status since no differences in nutritional status were found between the two groups. Both groups had a reduced energy intake and weight loss during radiotherapy. In the control group diarrhoea increased fatigue and had negative effects on physical functioning and role functioning. The intervention did not lead to differences in late radiation injury and chronic diarrhoea 3-4 years after treatment but diarrhoea was most prominent in the control group. Diarrhoea as a late effect increased fatigue and had a negative influence on social well being.</p>