Search

The article discusses the potential for lyprinol (LYP), a stabilised lipid extract of New Zealand Green Lipped Mussel, to serve as preventive treatment for inflammatory bowel disease (IBD) based on a study in South Australia. The effect of LYP and fish oil (FO) pre-treatments in mice with IBD was compared. The mice were treated with fish oil, olive oil (OO) and LYP and their body weight and disease activity index (DAI) scores were recorded daily. The results indicated that FO treatment had not been considered beneficial in treating IBD compared with OO.

Staphylococcus aureus (S. aureus) is one of the most common wound pathogens with increased resistance towards currently available antimicrobials. S. aureus biofilms lead to increase wound chronicity and delayed healing. Chitosan-dextran hydrogel (Chitogel) loaded with the hydroxypyridinone-derived iron chelator Deferiprone (Def) and the heme analogue Gallium-Protoporphyrin (GaPP) have previously been shown to have antimicrobial effects in clinical sinusitis. In this study, the efficacy of Chitogel loaded with Def, GaPP and a combination of Def and GaPP, were investigated in an S. aureus biofilm infected wound murine model over 10 days of treatment. Bacterial wound burden was monitored daily showing a significant decrease in bacterial bioburden on days 6 and 8 when treated with Def-GaPP Chitogel (log 10 1.0 and 1.2 reduction vs control, respectively). The current study demonstrates that the combination of Def-GaPP delivered in a Chitogel in vivo is not only effective in reducing S. aureus biofilm infection, but also improves cutaneous healing via effects on reduced inflammation, promotion of anti-inflammatory macrophage phenotype and marked early collagen deposition in the wound bed. This delivery platform presents a promising alternative non-toxic, antibacterial, wound-promoting treatment as a novel approach for the management of S. aureus wound infections that warrants further clinical investigation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Peter J Wormald reports equipment, drugs, or supplies were provided by Chitogel Pty Ltd. Peter J Wormald reports a relationship with Chitogel Pty Ltd that includes: equity or stocks. Peter J Wormald and Sarah Vreudge have patent pending to University of Adelaide., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Neurodegenerative diseases (NDDs) are incapacitating disorders that result in progressive motor and cognitive impairment. These diseases include Alzheimer's disease, the most common cause of dementia, frontotemporal dementia, amyotrophic lateral sclerosis, dementia with Lewy bodies, Parkinson's, Huntington's, Friedreich's ataxia, and prion disease. Dementia causing NDDs impose a high social and economic burden on communities around the world. Rapid growth in knowledge regarding the pathogenic mechanisms and disease-associated biomarkers of these diseases in the past few decades have accelerated the development of new diagnostic methods and therapeutic opportunities. Continuous effort is being applied to the development of more advanced, easy-to-apply and reliable methods of diagnosis, that are able to identify disease manifestation at its earliest stages and before clinical symptoms become apparent. Development of these diagnostic tools are essential in aiding effective disease management through accurate monitoring of disease progression, timely application of therapeutics and evaluation of treatment efficacy. Recently, several studies have identified novel biomarkers based on compounds in exhaled breath associated with specific NDDs. The use of breath testing, as a means of monitoring neurodegenerative disease onset and progression, has the potential to have a significant impact on augmenting the diagnosis of NDDs as the approach is non-invasive, relatively cost effective and straight forward to implement. This review highlights key features of current diagnostic methods utilised to identify NDDs, and describes the potential application and limitations associated with the use of breath analysis for disease diagnosis and progression monitoring., (Copyright © 2018. Published by Elsevier B.V.)

Metabolic cages are a type of housing used in biomedical research. Metabolic cage housing has been demonstrated to elicit behavioural and physiological changes in rodents housed within them. The nature of this effect has been characterized as anxiogenic. However, few studies have evaluated positive affect in response to metabolic cage housing and the interaction between this, sex and traditional physiological measures of stress. Cognitive biasing, as measured through a judgment bias paradigm has proven a reliable measure of animal affective state, particularly through its ability to measure positive affect. The current study investigated differences in cognitive biasing between male and female rats when transferred from open-top, grouped housing to a metabolic cage. Rats (Rattus norvegicus) (n=60) were trained in a judgment bias paradigm previously validated for use in the rat model. Upon exposure to an intermediate, ambiguous probe rats responded with either an optimistic or pessimistic decision. The animals were also subjected to the sucrose preference test to identify the presence of anhedonia. Faecal corticosterone and changes in adrenal tyrosine hydroxylase were also measured to establish whether a stress-like state was experienced. There was a significant interaction between sex and metabolic cage housing on the number of optimistic decisions made F (1, 56)=7.461, p=0.008. Female rats that remained in control housing responded with a reduced number of days featuring an optimistic decision compared to males in control housing (p=0.036). However, both males and females responded with significantly fewer optimistic decisions in the metabolic cage compared to control (p<0.001). There was a significant negative correlation between treatment and sucrose consumption (r pb =-0.654, n=195, p<0.001). There was also a significant sex effect for faecal corticosterone concentrations F (1, 30)=6.305, p=0.018) with female rats (4.050±1.285), displaying greater corticosterone concentrations than males (2.291±0.495). No differences between treatment were observed for either corticosterone or tyrosine hydroxylase levels. This data demonstrates that movement into a metabolic cage resulted in rats displaying significantly greater pessimistic cognitive biases as determined through the judgment bias test. Interestingly, male rats that remained in control housing demonstrated cognitive biases that were not equivalent to female rats. Furthermore, despite a behavioural change being evident, a physiological change in corticosterone or tyrosine hydroxylase levels was not observed., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)

Blood tests are a seemingly basic investigation, but are often a vital part of directing patient management. Despite the importance of this everyday process, we indentified the potential for improvement of the current phlebotomy service in our hospital, as both junior doctors and phlebotomists reported a lack of communication and standardised practice across the wards. Resulting delays in obtaining blood test results can impact detrimentally on patient safety and management. We designed a survey which highlighted inefficient handovers and discrepancies between wards as driving factors behind this. We therefore aimed to improve communication between phlebotomists and doctors, as well as the overall organisation of the service. This took the form of the "Phlebotomy Box," a box file system offering a set location for blood stickers to be situated. The box concept was optimised on a series of medical and surgical wards, incorporating multidisciplinary feedback from relevant teams. We measured how many untaken bloods were handed over to medical staff continuously, both pre- and post implementation of the phlebotomy box. Our baseline ward demonstrated poor handover rates of untaken bloods, ranging from 0% to 40%. This increased to a consistent 100% following introduction of the Phlebotomy Box and ongoing staff education. Once optimised, the box was trialled on a further two medical wards and one surgical ward, achieving 100% handover from an initial 0% to 67%. Quantitative improvement was also reflected qualitatively in widespread staff surveys, with overwhelmingly positive support and acceptance. In summary, the Phlebotomy Box innovation has led to 100% of untaken bloods being effectively handed over. We have demonstrated a significant improvement in communication and efficiency within the phlebotomy service, with tangible benefits to patient care, as minimising time lags can prevent delays in clinical decisions. The phlebotomy box represents a simplistic, sustainable intervention that could be easily replicated in other Trusts.

The current systems of care for dying persons, the people caring for them, and the bereaved operate in ways that frequently lack sufficient sensitivity to their needs. We describe a new model for dying, death, and loss that adopts a public health approach. Specifically, we describe a deliberative process that resulted in a charter for a public health approach to dying, death, and loss. Modeled after the World Health Organization's 1986 Ottawa Charter, our charter includes a call to action. It has the potential to bring about significant change on local, societal, and global levels as exemplified by four projects from three countries. Public health and end-of-life services and organizations need to form partnerships with the community to develop a public health approach to dying, death, and loss. Learning from each other, they will affirm and enhance community beliefs and practices that make death part of life.

Conducting research in the deployed environment is challenging but if the various obstacles are overcome then the data captured can be vital in developing future treatment strategies. Perhaps the most important aspect is having an enthusiastic individual who is dedicated to research and can thus concentrate on maximising the potential of this unique environment.

Background: Fatty acids are classified as short-chain (SCFA), medium-chain (MCFA) or long-chain and hold promise as adjunctive chemotherapeutic agents for the treatment of colorectal cancer. The antineoplastic potential of MCFA remains underexplored; accordingly, we compared the MCFA lauric acid (C12:0) to the SCFA butyrate (C4:0) in terms of their capacity to induce apoptosis, modify glutathione (GSH) levels, generate reactive oxygen species (ROS), and modify phases of the cell cycle in Caco-2 and IEC-6 intestinal cell lines., Methods: Caco-2 and IEC-6 cells were treated with lauric acid, butyrate, or vehicle controls. Apoptosis, ROS, and cell cycle analysis were determined by flow cytometry. GSH availability was assessed by enzymology., Results: Lauric acid induced apoptosis in Caco-2 (p < 0.05) and IEC-6 cells (p < 0.05) compared to butyrate. In Caco-2 cells, lauric acid reduced GSH availability and generated ROS compared to butyrate (p < 0.05). Lauric acid reduced Caco-2 and IEC-6 cells in G0/G1and arrested cells in the S and G2/M phases. Lauric acid induced apoptosis in IEC-6 cells compared to butyrate (p < 0.05). Butyrate protected IEC-6 cells from ROS-induced damage, whereas lauric acid induced high levels of ROS compared to butyrate., Conclusion: Compared to butyrate, lauric acid displayed preferential antineoplastic properties, including induction of apoptosis in a CRC cell line.

Reasons for Performing the Study: Prior to the start of endogenous production of immunoglobulins (Igs), absorption of maternal Igs is important to protect against pathogens in the early neonatal period. It is possible that mare- or foal-associated factors may influence neonatal IgA concentrations., Objectives: The temporal relationships among serum and milk IgA concentrations in Thoroughbred mare-foal pairs were explored to determine if periparturient mare- and foal-associated factors contribute to the prediction of foal serum IgA concentrations., Methods: Blood and milk samples as well as complete veterinary records, were collected for 84 Thoroughbred mare-foal pairs from one month before to 2 months after parturition. Samples were tested using enzyme-linked immunosorbent assay (ELISA) for concentrations of IgA. Pairwise correlation coefficients were estimated (P < 0.01) and simple linear regression used to investigate unconditional associations between mare IgA levels, mare and foal risk factors and foal serum IgA concentration at 12 h. Backwards, stepwise elimination of nonsignificant factors was used to create a final model., Results: There were significant temporal relationships among mare serum IgA and among colostrum and milk IgA concentrations within mares (P < 0.01). Mare serum IgA concentrations up to one month before parturition were associated with foal serum IgA concentrations at all time points and with colostrum and milk IgA concentrations. Mare serum IgA at -28 days and parity were associated with foal serum IgA concentration at 12 h (P < 0.001)., Conclusions: Mare serum IgA concentrations up to 28 days before parturition, together with mare parity, are indicative of neonatal foal serum IgA concentrations., Potential Relevance: Mare serum and colostrum IgA concentrations may be useful peripartum predictors of neonatal mucosal immune status, enabling earlier intervention to prevent the consequences of mucosal infections.

Background: The aim of this study was to explore the current status of end-of-life care and dying of people with intellectual disability based on the experiences of staff in community living services., Materials and Methods: Focus groups and individual interviews were conducted, guided by grounded theory methodology., Results: The current status of end-of-life care and dying comprised five key 'issues': knowledge of dying, ethical values, the where of caring, the how of caring and post-death caring. These issues occurred in relationship with 'partners', including the dying person, other clients, fellow staff, family, external health services and the coroner., Conclusions: End-of-life care represents a complex interaction between the care issues and the partners involved in care. Despite this complexity, staff were committed to the provision of end-of-life care., (© 2012 Blackwell Publishing Ltd.)

Complaints of sexual impropriety against healthcare practitioners are escalating. Professionalism in the practitioner-patient relationship and the role-based trust in health care do not allow crossing of sexual boundaries. Communication with patients is key to prevent erroneous allegations of sexual misconduct. The intimate examination is difficult to define. A chaperone present during an intimate examination protects the patient and practitioner and should be considered a risk reduction strategy in practice.

Purpose: In order to determine the sensitivity and specificity of the test and to optimize experimental conditions utilizing the SBT in a rat model of chemotherapy-induced small intestinal damage., Methods: Initially, a 13C-sucrose dose-response study was performed in rats to determine an optimal sucrose concentration for the SBT; then applied to assess chemotherapy-induced intestinal damage. A further study was conducted to establish a SBT time-course of methotrexate-induced small intestinal damage and repair. Animals were killed at 96 or 144 h., Results: A sucrose concentration of 0.25 g/ml was optimal (20% CV) for reproducibility and detection of intestinal damage. Maximal damage occurred at 72 h, small intestinal repair was initiated by 96 h and continued at 144 h post-MTX, as determined by the SBT and confirmed by biochemical analyses. Levels of sensitivity and specificity for the SBT were 98 and 94%, respectively., Conclusions: The SBT is a reliable non-invasive marker of small intestinal health and damage with a high degree of sensitivity and specificity.

Inflammatory bowel disease (IBD) is a chronic relapsing disorder that is increasing in prevalence in Western society and has been linked to the development of colorectal cancer. There remains no definitive treatment for IBD, hence recent investigations have focused on the development of new therapeutics, including probiotics, which can reduce intestinal inflammation and restore balance to the gastrointestinal microbiota. Probiotics are currently being studied in greater detail, albeit predominantly in animal models of IBD. Clinical studies have yielded promising findings and justify further investigation. Furthermore, the use of inactivated probiotics as well as the soluble products produced by these bacteria has demonstrated therapeutic potential, and may in fact be more suitable, as there is no risk of sepsis associated with their administration and they can be manufactured with greater quality control. Further research is essential to define the mechanism and source of probiotic action, and to identify more efficacious strains, while future clinical trials must focus on determining whether the bacterial and genetic profiles of IBD patients influence the effectiveness of treatment., (Copyright © 2009 Crohn's & Colitis Foundation of America, Inc.)

A unique model of formula feeding in the neonatal rat was utilized to investigate the effects of an enterally delivered artificial milk formula on clinically relevant immunological and biological characteristics in the gut, compared to naturally reared pups. Hooded Wistar rat pups were randomly allocated to two treatment groups: formula-fed (FF) or naturally suckled (NS). A flexible silastic intra-gastric cannula was surgically implanted into the FF pups, through which an artificial rat milk supplement was continuously delivered from day 4 to day 10 of life. Rat pups were sacrificed at 10 days of age. Body weight, small intestinal weight, mucosal CD8(+) cell numbers, and ileal lactase activity in FF animals were significantly decreased compared to their NS counterparts (P < 0.05). Numbers of eosinophils, mucosal mast cells, CD4(+) T-cells, ileal villus height and gastric emptying times were significantly increased in FF pups (P < 0.05). We have developed a new rat model of artificial feeding which possesses important immunological and biological similarities to the premature human infant.

Small intestinal permeability was employed to assess the efficacy of commercially available yoghurts containing probiotics in a rat model of methotrexate (MTX)-induced mucositis. Male Sprague-Dawley rats were allocated to four groups (n = 8): MTX + water, MTX + cow's milk yoghurt (CY; fermented with Lactobacillus johnsonii), MTX + sheep's milk yoghurt (SY; containing Lactobacillus bulgaricus and Streptococcus thermophilus), and saline. Treatment gavage occurred twice daily for 7 days pre-MTX and 5 days post-MTX. Intestinal permeability was assessed on days -7, -1, 2, and 5 of the trial. Intestinal sections were collected at sacrifice for histological and biochemical analyses. Histology revealed that rats receiving CY and SY did not have a significantly damaged duodenum compared to controls. However, an improved small intestinal barrier function was evident, determined by a decreased lactulose/mannitol ratio. Probiotics containing SY and CY may be useful in preventing disruption to intestinal barrier function in MTX-induced mucositis.

Mucins possess potential binding sites for both commensal and pathogenic organisms and may perform a defensive role during establishment of the intestinal barrier. To observe the effects of bacteria on intestinal goblet cell mucin production during posthatch development, differences in the small intestine of conventionally reared (CR) and low bacterial load (LBL) broiler chicks were examined. Jejunal and ileal goblet cells were stained with either periodic acid-Schiff stain or high iron diaminealcian blue pH 2.5 to discriminate among neutral, sulfated, and sialylated acidic mucins. Total goblet cell numbers and morphology of goblet cells containing neutral and acidic mucins did not differ significantly between CR and LBL birds. However, significant differences in acidic mucin composition from primarily sulfated to an increase in sialylated sugars at d 4 posthatch were observed in CR chicks, with greater numbers of jejunal and ileal goblet cells displaying this mucin type (CR, 0.5 +/- 0.1 x 10(3) cells/mm(2); LBL, 0.04 +/- 0.02 x10(3) cells/mm(2)). This change in mucin profile in response to bacterial colonization suggests a potential role as a protective mechanism against pathogenic invasion of the intestinal mucosa during early development.

Zinc (Zn) and its binding protein metallothionein (MT) have been proposed to suppress the disease activity in ulcerative colitis. To determine the role of Zn and MT in the dextran sulfate sodium (DSS)-induced model of colitis in mice, a DSS dose-response study was conducted in male C57BL/6 wild-type (MT+/+) and MT-null (MT-/-) mice by supplementing 2%, 3%, and 4% DSS in the drinking water for 6 days. In the intervention study, colitis was induced with 2% DSS, Zn (24 mg/ml as ZnO) was gavaged (0.1 ml) daily, concurrent with DSS administration, and the disease activity index (DAI) was scored daily. Histology, MT levels, and myeloperoxidase (MPO) activity were determined. DAI was increased (P<0.05) by 16% and 21% with 3% and 4% concentrations of DSS, respectively, compared to 2%, evident after 5 days of DSS administration. MPO activity was increased in MT+/+ compared to MT-/- mice and those receiving DSS. Zn administration had a 50% (P<0.05) lower DAI compared to DSS alone. Zn partially prevented the distal colon of MT+/+ by 47% from DSS-induced damage compared to MT-/- mice. MT did not prevent DSS-induced colitis and Zn was partially effective in amelioration of DSS-induced colitis.

With the intensified use of chemotherapy and improved survival rates for childhood malignancies, it has become increasingly apparent that some children or adult survivors show poor bone growth and develop osteoporosis. As a step to investigate underlying mechanisms, this project examined short-term effects in rats of chemotherapy agent 5-fluorouracil (5-FU) on cell proliferation, apoptosis, and bone formation at tibial growth plate cartilage and its adjacent bone-forming region metaphysis. In addition, since insulin-like growth factor (IGF-I) is important for bone growth, we examined whether IGF-I pretreatment would potentially protect growth plate cartilage and bone cells from chemotherapy damage. Two days after a single high dose of 5-FU injection, proliferation of growth plate chondrocytes and metaphyseal osteoblasts/preosteoblasts was dramatically suppressed, and apoptosis was induced among osteoblasts and preosteoblasts. As a result, there was a reduction in the chondrocyte number and zonal height at the proliferative zone and a decline in the number of osteoblasts and preosteoblasts on the metaphyseal trabecular bone surface. At day 2, no obvious deleterious effects were observed on the height of the growth plate hypertrophic zone and the bone volume fraction of the metaphyseal primary spongiosa trabeculae. At day 10, while cell proliferation and growth plate structure returned to normal, there were slight decreases in trabecular bone volume, body length increase, and tibial length. While pretreatment with 1-week IGF-I systemic infusion did not attenuate the suppressive effect of 5-FU on proliferation in both growth plate and metaphysis, it significantly diminished apoptotic induction in metaphysis. These results indicate that growth plate cartilage chondrocytes and metaphyseal bone cells are sensitive to chemotherapy drug 5-FU and that IGF-I pretreatment has some anti-apoptotic protective effects on metaphyseal bone osteoblasts and preosteoblasts.

Background: Ussing chambers are commonly utilized for in vitro investigations into gastrointestinal permeability. However, their sensitivity and applicability to the small intestine have not been well characterized., Methods: In order to investigate the effects of experimentally induced damage and the relative contribution of the mucosa and muscularis externa layers to transmural permeability in the small intestine, stomach and colon, normal rat intestinal tissues were mounted in Ussing chambers with or without removal of the muscularis externa or mucosal layers. Gastric tissues were damaged in vivo by exposure to indomethacin (100 mg kg(-1)), while ileal tissues were damaged in vitro by 0.4 M NaCl. Tissue damage was assessed histologically, while permeability parameters included conductance (G), potential difference (PD) and mucosal to serosal flux of horseradish peroxidase (HRP)., Results: Damage localized to the tissue edges (edge damage) accounted for 25%-50% of the exposed epithelial length in the ileum, while less than 20% of stomach and colon epithelium was affected by edge damage. In the damaged stomach, a 20% reduction in epithelialization was accompanied by increases in G (P < 0.001) and HRP (P < 0.01) flux. Removal of the muscularis externa did not affect mucosal viability in the undamaged ileum or colon although HRP flux in the colon, but not ileum, was increased (P < 0.01). Removal of the ileal mucosa produced increases in G and HRP flux, while PD was maintained., Conclusion: We conclude that the Ussing chamber technique is suitable for application to studies of gastric and colonic permeability in rats. However, owing to the prevalence and extent of edge damage in the small intestine, we would caution against the use of this technique for permeability studies in this region of the gastrointestinal tract in the rat.

Objective: To compare labour outcomes using aggressive or expectant management protocols., Design: Randomised trial., Setting: Pretoria Academic Complex, South Africa. It serves an indigent urban population., Population: Healthy nulliparous women in active labour, at term, with a health singleton pregnancy and cephalic presentation., Methods: The women were randomised to either aggressive (n = 344) or expectant (n = 350) management protocols. Aggressive management entailed using a single line partogram, a vaginal examination every two hours and use of an oxytocin infusion if the line was crossed. Expectant management entailed using a two line partogram, with the alert line and a parallel action line four hours to the right, with a vaginal examination every four hours. If the action line was reached, oxytocin was started. The women were reassessed every two hours thereafter. Analgesia was prescribed on request., Main Outcome Measures: Mode of birth, use of oxytocin and analgesia and neonatal outcome., Results: The groups were similar with respect to maternal age, cervical dilation at trial entry, number crossing the alert line and birthweight of the infants. Significantly fewer women managed aggressively had caesarean sections (16.0%) than those managed expectantly (23.4%) (relative risk [RR] 0.68, 95% confidence intervals [CI] 0.50, 0.93). Significantly more oxytocin was used in the aggressive management group, but there was no difference with respect to the use of analgesia or episiotomy or in neonatal outcome with respect to the Apgar score at 1 or 10 minutes. There were three perinatal deaths. One woman was found to have an intrauterine death before trial entry and the other two were in the aggressive management group but did not receive oxytocin. Compliance by staff was poor in the aggressive management group., Conclusions: Aggressive management of labour reduces the caesarean section rate in nulliparous women but requires more intensive nursing.

A biologically active extract containing bovine whey proteins, whey growth factor extract-A (WGFE-A) was administered topically to the oral mucosa of hamsters and its ability to prevent and treat chemotherapy-induced oral mucositis investigated. Oral mucositis was induced in Syrian golden hamsters through a combination treatment of the antimetabolite chemotherapy drug 5-fluorouracil (5-FU), and mild abrasion of the cheek pouch. WGFE-A administered to the oral mucosa via hydrogel and liquid treatments, pre and concurrent to 5-FU therapy, resulted in significantly reduced mucosal ulceration. The protective effect was dose dependent with greatest benefit from WGFE-A doses applied at 4.2 mg/ml gel and 14 mg/ml mouthwash (P<0.01). The protective activity of WGFE-A also appeared related to mode of delivery. Administration of WGFE-A from an alternate vehicle Orabase(R) did not alleviate mucositis compared to WGFE-A applied in hydrogel. When administered continuously after the chemotherapy schedule, WGFE-A failed to reduce ulcer area when applied over a 12-day period. In a separate study, cell cycle staining indicated that cheek pouch mucosal epithelial cells pre-exposed to WGFE-A in-vivo showed a reduced rate of proliferation, measured as a 21% reduction in the bromodeoxyuridine (BrdU) cell labelling index (P<0.04). This was consistent with a protective mode of WGFE-A action against anti-metabolites such as 5-FU which target rapidly dividing cells. The results were also consistent with recent in vitro data showing protective properties from WGFE-A administered to epithelial cells given pre/concurrent to chemotherapy exposure. WGFE-A is known to contain mitogens which stimulate cells of mesenchymal origin and inhibit epithelial cell growth in culture. Several WGFE-A constituents are likely to confer protective effects on the cheek mucosa, including anti-proliferative, anti-apoptotic and anti-microbial factors. WGFE-A provides a potentially valuable source of topically delivered proteins for clinical application in preventing severe oral mucositis caused by chemotherapy.

Objectives: Inflammatory bowel disease (IBD) is usually diagnosed as a result of symptoms but occasionally is found during investigation for other conditions. An earlier report from Nottingham had found a high prevalence of previously undetected "asymptomatic" IBD detected as a result of colorectal cancer screening, and the aim of this study was to reassess the prevalence, symptoms, and outcome in these patients., Methods: We investigated subjects found to be fecal occult blood (FOB) positive in a randomized trial of FOB screening for colorectal cancer. All FOB-positive subjects were investigated by colonoscopy or flexible sigmoidoscopy and barium enema. Subjects with IBD were referred back to their general practitioner for any further investigation and treatment., Results: Seventy-five thousand two hundred fifty-three subjects (aged 45-74) were sent FOB tests and 44,838 (60%) completed a series of tests on one or more occasions. Of 133,000 test series, 1.5% were positive. During investigation 53 cases of previously undetected IBD (52 of ulcerative colitis) were found; 52% (27/52) had proctosigmoiditis only, whereas 25% (13/52) had pancolitis. Only 17% (9/52) were completely asymptomatic, with a half or more reporting some rectal bleeding (54%) or diarrhea (50%). The overall prevalence of undetected ulcerative colitis was 69/10(5) (95% CI = 50-88/10(5)) in people offered screening and 116/10(5) (95% CI = 85-147/10(5)) in people accepting screening and was higher in men. Of 32 subjects followed up 2-12 yr after diagnosis, 91% (29) continued to have few or no symptoms, with only 12 currently receiving any treatment for their colitis., Conclusions: In comparison with detected disease, undetected ulcerative colitis is relatively common but does usually cause some symptoms. It generally appears to follow a benign course, but a significant proportion have extensive colitis and may therefore be at an increased risk of colorectal cancer.

Background and Aim: T-cell activation, mediated by the interaction with major histocompatibility complex (MHC)-peptide complexes and B7 costimulatory molecules on antigen-presenting cells, is an essential event in the pathogenesis of inflammatory bowel disease (IBD). We investigated the expression of B7 costimulatory molecules on cells in the colon in an experimental mouse model of IBD to determine whether the B7/ligand interaction could provide a target for therapeutic intervention in IBD., Methods: Experimental colitis was induced in mice by oral consumption of water substituted with 5% dextran sulfate sodium (DSS). Mice (n=4) were killed 1, 2, 3, 4 and 7 days after commencing DSS consumption, and colonic tissue was collected and examined immunohistochemically for T cells, B cells, macrophages and cells expressing B7-1 or B7-2., Results: Compared to control mice drinking water, macrophage numbers in the colonic epithelium were elevated sevenfold by day 1 and T cells were elevated threefold by day 3 following commencement of DSS consumption. Numbers of infiltrating B7-positive (B7+) cells were not significantly elevated until day 7 when B7-1+, B7-2+ cells and macrophages were increased 20-fold compared to normal mice., Conclusion: These results demonstrate that an initial and rapid infiltration of the colonic epithelium by B7-negative macrophages is followed by an infiltration of T cells and subsequent upregulation of the B7 costimulatory molecules potentiating the inflammatory reaction in this disease model. These results suggest an intervention strategy based on the blockade of the B7-costimulatory axis could find application in the treatment of inflammatory bowel disease.

Background: Induction of labour is a common obstetric intervention. Amniotomy alone for induction of labour is reviewed separately and oxytocin alone for induction of labour is being prepared for inclusion in The Cochrane Library. This review will address the use of the combination of these two methods for induction of labour in the third trimester. This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology., Objectives: To determine, from the best available evidence, the efficacy and safety of amniotomy and intravenous oxytocin for third trimester induction of labour., Search Strategy: The Cochrane Pregnancy and Childbirth Group Trials Register, the Cochrane Controlled Trials Register and reference lists of articles were searched. Date of last search: May 2001., Selection Criteria: The criteria for inclusion included the following: (1) clinical trials comparing amniotomy plus intravenous oxytocin used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods; (2) random allocation to the treatment or control group; (3) adequate allocation concealment; (4) violations of allocated management not sufficient to materially affect conclusions; (5) clinically meaningful outcome measures reported; (6) data available for analysis according to the random allocation; (7) missing data insufficient to materially affect the conclusions., Data Collection and Analysis: Trial quality assessment and data extraction were done by both reviewers. A strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. The initial data extraction was done centrally, and incorporated into a series of primary reviews arranged by methods of induction of labour, following a standardised methodology. The data is to be extracted from the primary reviews into a series of secondary reviews, arranged by category of woman., Main Results: Seventeen trials involving 2566 women were included. Amniotomy and intravenous oxytocin were found to result in fewer women being undelivered vaginally at 24 hours than amniotomy alone (relative risk (RR) 0.03, 95% confidence intervals (CI) 0.001-0.49). This finding was based on the results of a single study of 100 women. As regards secondary results amniotomy and intravenous oxytocin resulted in significantly fewer instrumental vaginal deliveries than placebo (RR 0.18, CI 0.05-0.58). Amniotomy and intravenous oxytocin resulted in more postpartum haemorrhage than vaginal prostaglandins (RR 5.5, CI 1.26-24.07). Significantly more women were also dissatisfied with amniotomy and intravenous oxytocin when compared with vaginal prostaglandins, RR 53, CI 3.32-846.51., Reviewer's Conclusions: Data on the effectiveness and safety of amniotomy and intravenous oxytocin are lacking. No recommendations for clinical practice can be made on the basis of this review. Amniotomy and intravenous oxytocin is a combination of two methods of induction of labour and both methods are utilised in clinical practice. If their use is to be continued it is important to compare the effectiveness and safety of these methods, and to define under which clinical circumstances one may be preferable to another.

Background and Aims: In addition to its beneficial effects on small intestinal mucosal development and repair, insulin-like growth factor (IGF)-I has also been reported to improve neural function in toxic neuropathies. It has recently been recognized that enteric neural abnormalities contribute to the small intestinal dysmotility observed during and after abdominal radiotherapy for gynecological and pelvic malignancy. The aim of the present study was to evaluate the effects of IGF-I (5 mg/kg per day) and the more potent analog LR3IGF-I (5 mg/kg per day) on neurally mediated ileal dysmotility following irradiation., Methods: Intestinal motor activity was recorded from 6-8 cm segments of explanted rat ileum using a miniaturized manometric technique during arterial perfusion with oxygenated fluorocarbon solution. Studies were performed 4 days after treatment with 10 Gy abdominal irradiation. At the time of irradiation, all rats underwent implantation of an osmotic mini-pump that contained 100 mmol/L acetic acid vehicle (n = 8), IGF-I (n = 8) or LR3IGF-I (n = 7). For each experiment, the total number of pressure waves, high-amplitude long-duration (defined as > 20 mmHg, > 6 s; HALD) pressure waves and long bursts (> 20) of pressure waves were determined. Ileal segments from 12 non-irradiated rats were used as controls for manometric studies. In radiotherapy treated animals, the degree of mucosal damage was determined using a standardized histologic scoring system., Results: The HALD pressure waves were infrequent in non-irradiated rats but occurred in all irradiated animals. Insulin-like growth factor-I and LR3IGF-I had no effect on the frequency, amplitude or migration characteristics of HALD pressure waves compared with vehicle. Histologic damage was reduced in animals that received IGF-I and LR3IGF-I compared with vehicle-treated animals., Conclusions: In radiation enteritis, IGF-I has no effect on neurally mediated small intestinal dysmotility while improving mucosal histology. The disparity between these results suggests that parallel but separate pathologic processes underlie mucosal and motor abnormalities in radiation enteritis.

Background: Misoprostol is a synthetic prostaglandin which has been used to induce labour. Oral use of the drug misoprostol may be convenient, but an overdose could cause uterine hyperstimulation and precipitate labour which may be life-threatening for both mother and fetus., Objectives: The objective of this review was to assess the effects of oral misoprostol used for labour induction in women with a viable fetus., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register., Selection Criteria: Randomised trials of oral misoprostol versus any other method, placebo or no treatment given to women with a viable fetus for induction of labour., Data Collection and Analysis: The selection of trials and data extraction were undertaken by one reviewer and independently checked by two other reviewers., Main Results: Five trials were included. In one placebo trial, oral misoprostol reduced the need for oxytocin infusion and shortened delivery time in women with prelabour rupture of membranes at term. In another trial, compared to vaginal prostaglandins, oral misoprostol reduced the need for oxytocin (relative risk 0.62, 95% confidence interval 0.47 to 0.82). Based on two trials, the caesarean section rate with oral misoprostol was 20. 2% (55/272) compared with 15.5% (42/270) for vaginal prostaglandins (relative risk 1.29, 95% confidence interval 0.90 to 1.86). Different doses (100 micrograms three hourly and 200 micrograms six hourly) were used in the two trials that compared oral with vaginal misoprostol. The caesarean section rate was 21.8% in the oral misoprostol group compared with 13.5% for vaginal misoprostol (relative risk 1.62, 95% confidence interval 0.85 to 3.09). The uterine hyperstimulation rate with oral misoprostol was 37.5% (36/96) compared with 28% (25/89) for vaginal misoprostol (relative risk 1.32, 95% confidence interval 0.86 to 2.04). There was significant heterogeneity between these two trials., Reviewer's Conclusions: Oral misoprostol may be an effective method for labour induction. However clinically effective oral regimens may have an unacceptably high incidence of uterine hyperstimulation and possibly uterine rupture.

Background: Insulin-like growth factor-I (IGF-I) is currently under evaluation for the treatment of a variety of chronic disease conditions. We investigated the safety of long-term IGF-I administration in a rat model of inflammatory bowel disease which predisposes to the development of dysplasia., Methods: Chronic consumption of dextran sulphate sodium (DSS) by rats manifests a colitis with dysplastic features. Rats consumed 2% DSS for 4 weeks when pumps were implanted to deliver either vehicle or IGF-I for 15 or 20 weeks while rats continued to consume DSS. Features of colitis and dysplasia were assessed at kill., Results: Compared to vehicle, 20 weeks IGF-I significantly increased body weight by 19% and total gut weight by 43%. Colonic crypt depth, proliferative compartment, labelling index, dysplasia, neoplasia and other indices of colitis were not significantly affected., Conclusions: Twenty weeks administration of IGF-I to rats induced growth of the intestine but did not affect the severity of experimentally-induced colitis or the incidence or progression of colonic dysplasia.

Trefoil factor TFF3 has been implicated in intestinal protection and repair. This study investigated the spatiotemporal relationship between TFF3 expression and morphological changes during intestinal damage and repair in a rat model of methotrexate-induced small intestinal mucositis. Intestinal tissues from rats with mucositis were collected daily for 10 days. Mucosal damage was characterized by an initial decrease in cell proliferation resulting in crypt loss, villus atrophy, and depletion of goblet cells, followed by hyperproliferation that lead to crypt and villus regeneration and mucous cell repopulation. TFF3 mRNA levels increased marginally during histological damage, and the cell population expressing TFF3 mRNA expanded from the usual goblet cells to include some nongoblet epithelial cells before goblet cell repopulation. TFF3 peptide, however, was depleted during histological damage and normalized during repair, mirroring the disappearance and repopulation of goblet cells. Although there is no temporal relationship between TFF3 levels and crypt hyperproliferation, confirming the nonmitogenic nature of TFF3, the coincidental normalization of TFF3 peptide with repopulation of goblet cells and mucin production after proliferative overshoot suggests that TFF3 may play a role in the remodeling phase of repair.

Background: Transforming growth factors (TGF-alpha and -beta1) play important roles in intestinal growth and repair. To further understand their roles in the pathophysiology of inflammatory bowel disease (IBD), this study examined changes in their expression in colonic mucosa of adolescents with IBD., Methods: TGF-alpha and -beta1 expression was examined by immunohistochemistry and in situ hybridization., Results: TGF-gamma immunostaining and mRNA labelling appeared unchanged in the epithelium of specimens with active IBD. Similarly, expression of epithelial TGF-beta1 remained unaltered in IBD. However, the numbers of TGF-beta1-positive cells, including T cells, neutrophils, and monocytes/macrophages, in the lamina propria increased during disease activity., Conclusions: Adolescent IBD is characterized by a normal expression of TGF-alpha and -beta1 peptide and mRNA in the colonic epithelium but by an increased density of TGF-beta1-positive immune cells in the lamina propria during disease activity, suggesting a role in inflammatory modulation in IBD.

Abdominal symptoms such as diarrhoea, abdominal cramps and vomiting are common during and after abdominal radiotherapy for gynaecological and pelvic malignancy. It has recently been recognized that small intestinal dysmotility may contribute to these symptoms but the underlying mechanisms are unclear in part because of the technical difficulties inherent in performing studies in irradiated small intestine. The aim of the current study was to evaluate small intestinal motor activity using perfused micromanometric techniques in 6-8-cm segments of ileum during arterial perfusion with isotonic oxygenated fluorocarbon solution. Intestinal segments from six rats were studied 4 days after treatment with 10 Gy abdominal irradiation. Ileal segments from nine nonirradiated animals acted as controls. For each experiment the total number of pressure waves, high-amplitude (> 20 mmHg, long-duration > 6 sec) pressure waves, and long (> 20 associated) bursts of pressure waves were determined. Irradiation had no effect on the overall number of pressure waves, but increased high-amplitude long-duration (HALD) pressure waves (248 vs 7, P < 0.01). In control animals HALD waves were localized to a single recording site but after radiotherapy 74% of HALD waves were temporally associated with similar pressure waves in other manometric channels. Forty-seven per cent of associated HALD waves migrated aborally. Retrograde migration of HALD waves was seen in five segments following irradiation. Irradiation abolished bursts of > 20 pressure waves.

Gut Zn homeostatic responses to low, replete, and excess dietary Zn (10, 150, and 400 mg Zn/kg, respectively) were compared in mice with (MT+/+) and without (MT-/-) metallothionein (MT) expression. MT concentrations decreased progressively from stomach (12.9 nmol Cd bound/g) to colon (4.6 nmol Cd bound/g). Small intestinal MT was increased in mice fed the 400-mg Zn/kg diet (+130%, duodenum; +56%, jejunum; +29%, terminal ileum), but not in the stomach, cecum and colon. Zn concentrations were much higher in the distal gut at increasing Zn intakes in MT+/+ mice but to a lesser extent in MT-/- mice. On the 10-mg Zn/kg diet, MT-/- mice had 45% more Zn in the jejunum/ileum than MT+/+ mice. In fasted (20 h) mice, Zn concentrations in all gut regions were similar to those of MT+/+ mice fed the 10-mg Zn/kg diet, irrespective of prior Zn intake or genotype. Liver MT quadrupled in mice fasted after the 10-mg Zn/kg diet but only doubled after the 400-mg Zn/kg diet, a trend also present in gut MT. Glucagon administration stimulated gut as well as liver MT, implicating it as a major component of the MT response to fasting. MT-/- mice had five times more variation than MT+/+ mice in plasma Zn over all dietary groups. Together, these findings demonstrate that without MT, there is little modification of regional gut Zn concentrations in response to extremes of dietary Zn and poorer regulation of Zn homeostasis.

Objective: To evaluate transcervical amnioinfusion for meconium stained amniotic fluid during labout., Design: Multicentre randomised controlled trial., Setting: Four urban academic hospitals in South Africa. Obstetric surveillance included the use of electronic fetal heart rate monitoring in most cases., Participants: Women in labour at term with moderate or thick meconium staining of the amniotic fluid., Interventions: Transcervical amnioinfusion of 800 mL saline at 15 mL per minute, followed by a maintenance infusion at 3 mL per minute. The control group received routine care. Blinding of the intervention was not possible., Main Outcome Measures: Caesarean section, meconium aspiration syndrome and perinatal mortality., Results: Caesarean section rates were similar (amnioinfusion group 70/167 vs control group 68/159; RR 0.98, 95% CI 0.76-1.26). The incidence of meconium aspiration syndrome was lower than expected on the basis of previous studies (4/162 vs 6/163; RR 0.67, 95% CI 0.19-2.33). There were no perinatal deaths. There were no significant differences between any of the subsidiary outcomes., Conclusions: This study concurred with three previous trials which found no effect of amnioinfusion for meconium-stained amniotic fluid on caesarean section rate, though the pooled data from all identified trials to date show a significant reduction. The findings with respect to meconium aspiration syndrome were inconclusive in this study alone because of the small number of babies affected, but the point estimate of the relative risk was consistent with the finding of a significant reduction in previous studies and with the Zimbabwe arm (CRAMP 2) of this study. Pooled data clearly support the use of amnioinfusion for meconium stained amniotic fluid to reduce the incidence of meconium aspiration syndrome.

Background: We tested the ability of insulin-like growth factor-I (IGF-I) to reduce damage to the intestinal mucosa (mucositis) in rats injected with methotrexate. IGF-I was infused concurrent with methotrexate administration and compared to IGF-I administered following the withdrawal of methotrexate., Methods: Rats were injected with methotrexate at the start of days 1, 2 and 3. IGF-I was infused for 5 days, commencing at the start of day 1 [concurrent administration] or at the start of day 4 [post-methotrexate administration]., Results: IGF-I administered coincident with methotrexate failed to restore mucosal integrity to the damaged small intestine. IGF-I administered post methotrexate stimulated regrowth of the damaged intestine, particularly the ileum, with 22%, 32% and 29% increases in small intestinal weight, ileal villus height and ileal crypt depth respectively., Conclusions: Following intestinal damage of methotrexate, IGF-I primarily induced growth of the distal small intestine. The ineffectiveness of concurrently administered IGF-I may have represented an IGF-I induced recruitment of proliferating epithelial cells to the anti-proliferative effects of methotrexate.