Cytokine mRNA quantification in histologically normal canine duodenal mucosa by real-time RT-PCR.

CD4(+) T helper cells are important for the regulation of immune responses in the intestinal mucosa and they exert their effects through the secretion of pro-inflammatory and immunomodulatory cytokines. Human patients with inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis have alterations in the normal intestinal cytokine profile. These cytokine abnormalities have been shown at both the protein and messenger RNA (mRNA) level. The role that mucosal cytokines play in the pathogenesis of canine IBD has only been investigated using semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis of gut tissue, as cytokine antisera are not available for this species. Real-time RT-PCR has been recognised to be a more accurate and sensitive method of quantifying mRNA transcripts, so in this study TaqMan real-time RT-PCR assays for the quantification of mRNA encoding IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-18, IFN-gamma, TNF-alpha and TGF-beta in canine intestinal mucosa were developed. The amount of these templates was quantified in normal canine duodenal mucosa (n = 8). IL-18, TGF-beta and TNF-alpha were found to be the most abundant transcripts, with IL-10 and IFN-gamma present at levels approximately 10-fold less. IL-2, IL-4, IL-5, IL-6 and IL-12 were the least abundant templates, with some RNA samples having no detectable mRNA copies. The methods developed in this study will form the basis of further work investigating the expression of mRNA encoding cytokines in mucosa from dogs with chronic enteropathies. In addition, these real-time PCR assays can also be used for the quantification of canine cytokine mRNA in other diseases.

Measurement of immunoglobulin concentrations in the feces of healthy dogs.

Selective immunoglobulin A (IgA) deficiency is the most common primary immunodeficiency in humans and may be associated with chronic gastrointestinal disease. This observation has led to the suggestion that the high susceptibility of German shepherd dogs (GSD) to chronic enteropathies is related to a deficiency in mucosal IgA production. Relative deficiencies of IgA has been reported in the serum, saliva, tears, and feces of GSD both with and without alimentary disease; however, the findings of different studies are not consistent. The aim of this study was to confirm whether a relative deficiency of IgA exists in the feces of GSD. Feces were collected from healthy GSD (n = 209), Labrador retrievers (n = 96), beagles (n = 19), and miniature schnauzers (n = 32). Fecal IgA, IgM, and IgG were measured by capture enzyme-linked immunosorbent assays. Fecal IgG concentrations in the four breed groups were not significantly different. IgA concentrations were significantly greater in miniature schnauzers than in GSD (P = 0.0003) and Labradors (P = 0.0004) but not significantly different from those in beagles. IgM concentrations were significantly greater in miniature schnauzers than in GSD (P < 0.0001), Labradors (P < 0.0001), and beagles (P = 0.0098). These findings do not support the hypothesis that GSD have a relative deficiency in fecal IgA. The differences in immunoglobulin concentrations measured from a single defecation, between individuals of the same breed and between breeds, as well as the lack of an internal control molecule, make the determination of a normal reference range for all dogs impossible. Therefore, the usefulness of fecal immunoglobulin quantification for the assessment of intestinal immunoglobulin secretion in dogs is limited.

Inter-digestive and post-prandial antro-pyloro-duodenal motor activity in humans: effect of 5-hydroxytryptamine 1 receptor agonism.

BACKGROUND: Little is known about the effect of 5-hydroxytryptamine 1 (5-HT(1)) receptor agonism on the co-ordinated motor activity of the gastric antrum, pylorus and duodenum under fasting and fed conditions. AIM: To evaluate the effect of sumatriptan, a 5-HT(1) agonist, on fasting and fed antro-pyloro-duodenal motility. METHODS: In study 1, antro-pyloro-duodenal motility was recorded for two phase IIIs of the migrating motor complex and then, following either a subcutaneous injection of sumatriptan 6 mg or saline control, for at least one additional phase III in 11 healthy volunteers (21-36 years). In study 2, the post-prandial motility was recorded for 3 h after either a subcutaneous injection of sumatriptan 6 mg or saline control in 10 healthy volunteers (18-36 years). RESULTS: Sumatriptan prolonged the migrating motor complex cycle (P = 0.009) by increasing the duration of phase II (P = 0.02) but not phases I and III. Post-prandially, sumatriptan reduced the activity index (P = 0.017) by reducing the frequency of co-ordinated motor activity involving the antrum and/or the duodenum (P < 0.05). CONCLUSION: 5-HT(1) receptor agonism increases the periodicity of the migrating motor complex and reduces the occurrence of post-prandial co-ordinated motor activity involving the gastric antrum, pylorus and duodenum.

Gut-focused hypnotherapy normalizes disordered rectal sensitivity in patients with irritable bowel syndrome.

BACKGROUND: We have previously shown that hypnotherapy alters rectal sensitivity in some patients with irritable bowel syndrome. However, this previous study used incremental volume distension of a latex balloon, which might be susceptible to subject response bias and might compromise the assessment of compliance. In addition, the study group was symptomatically rather than physiologically defined. AIM: To assess the effect of hypnotherapy on rectal sensitivity in hypersensitive, hyposensitive and normally sensitive irritable bowel syndrome patients using a distension technique (barostat) that addresses these technical issues. METHODS: Twenty-three irritable bowel syndrome (Rome I) patients (aged 24-72 years) were assessed before and after 12 weeks of hypnotherapy in terms of rectal sensitivity, symptomatology, anxiety and depression. Normal values for sensitivity were established in 17 healthy volunteers (aged 20-55 years). RESULTS: Compared with controls, 10 patients were hypersensitive, seven hyposensitive and six normally sensitive before treatment. Following hypnotherapy, the mean pain sensory threshold increased in the hypersensitive group (P = 0.04) and decreased in the hyposensitive group, although the latter failed to reach statistical significance (P = 0.19). Normal sensory perception was unchanged. Sensory improvement in the hypersensitive patients tended to correlate with a reduction in abdominal pain (r = 0.714, P = 0.07). CONCLUSION: Hypnotherapy improves abnormal sensory perception in irritable bowel syndrome, leaving normal sensation unchanged.

Visceral sensation and emotion: a study using hypnosis.

BACKGROUND AND OBJECTIVES: We have previously shown that hypnosis can be used to study the effect of different emotions on the motility of the gastrointestinal tract. These studies demonstrated that both anger and excitement increased colonic motility while happiness led to a reduction. The purpose of this study was to investigate the effect of hypnotically induced emotion on the visceral sensitivity of the gut. METHODS: Sensory responses to balloon distension of the rectum and compliance were assessed in 20 patients with irritable bowel syndrome (IBS) (aged 17-64 years; 17 female) diagnosed by the Rome I criteria. Patients were studied on four separate occasions in random order either awake (control) or in hypnosis, during which anger, happiness, or relaxation (neutral emotion) were induced. RESULTS: Hypnotic relaxation increased the distension volume required to induce discomfort (p=0.05) while anger reduced this threshold compared with relaxation (p<0.05), happiness (p<0.01), and awake conditions (p<0.001). Happiness did not further alter sensitivity from that observed during relaxation. There were no associated changes in rectal compliance or wall tension. CONCLUSIONS: Further to our previous observations on motility, this study shows that emotion can also affect an IBS patient's perception of rectal distension and demonstrates the critical role of the mind in modulating gastrointestinal physiology. These results emphasise how awareness of the emotional state of the patient is important when either measuring visceral sensitivity or treating IBS.

Water-soluble luminal contents of the gut of the earthworm Lumbricus terrestris L. and their physiological significance.

In the post-gizzard gut of the earthworm Lumbricus terrestris, distinguishing the functions of the luminal epithelium from those of the chloragogenous tissue has been hindered by the close apposition of these two tissues. Moreover, both tissues may have different functions from the anterior to the posterior of the animal. We analyzed the gut luminal contents of L. terrestris so as to gain a better understanding of the function of the luminal epithelium. The intestine was divided into four regions from anterior to posterior, and the water-soluble portion of the luminal contents of these four regions was analyzed for protease and amylase activity, calcium and ammonium ions, and protein. The same four regions of the gut wall were analyzed for glutamate dehydrogenase (GDH) and serine dehydratase (SDH) to determine their location with reference to the site of ammonia production. We observed high levels of proteases, amylase, protein and calcium ions in the gut luminal contents of the first two regions, and a significant decline of all four variables in region III. Conversely, ammonia was low in the gut contents of regions I and II but rose sharply in region III, which was also the region to which the tissue enzymes GDH and SDH were localized. The ammonia content of earthworm casts was observed to be much higher than that of the surrounding soil. These data are presented as partial evidence for the proposal that the excretory ammonia produced by feeding earthworms is a product of the luminal epithelium of region III of the gut. It is also proposed that ammonia and calcium may function as ion-exchangers in the absorptive function of the earthworm gut.

Illness Identity and the Self-regulatory Model in Recovery from Early Stage Gynaecological Cancer.

Women in recovery from early stage gynaecological cancer have extremely good survival and low recurrence rates. Despite this, women continue to feel vulnerable to cancer recurrence for years after treatment. Semi-structured interviews were utilized to explore the factors involved in recovery from gynaecological cancer. This article argues that the illness identity of gynaecological cancer perpetuates a vulnerability to cancer recurrence. The absence of self-diagnosis prior to medical diagnosis is important in the formation of gynaecological cancer illness identity. A lack of self-diagnosis may be due to the 'normalization' of initial symptomatology. It is suggested that illness identity is responsible for maintaining fears of symptom-free cancer recurrence. The self-regulatory model is employed to explore this process, looking in particular at the reinforcement of reassurance needs.

What are the factors associated with the follow-up preferences of women in long-term remission from gynaecological cancer?

We set out to examine factors associated with follow up preferences of women attending routine hospital follow up after treatment for early stage gynaecological cancer. This was a retrospective cohort study, using hospital records and questionnaire data, and was based in North Staffordshire, UK. Fifty-four women, who had undergone successful treatment for early stage gynaecological cancer and currently attending routine hospital follow up appointments, were studied. Follow-up preferences were established using a specially designed questionnaire. A questionnaire package containing psychological and demographic measures was used. Clinical details including site and stage of disease, treatment and follow-up type were obtained from medical records. There were no significant demographic or clinical differences between the women with preference for hospital follow-up and those women with a preference for discharge. Women with a preference for follow-up were found to have significantly higher anxiety (as measured by the MAC anxiety scale). These results were not found for the other anxiety scales (STAI and HADS). Three predictor variables (MAC anxiety, Education and Car ownership) were found to predict significantly group membership. It is not possible to predict follow-up needs using demographic, clinical or psychological factors. Follow-up needs are achieved through effective medical communication. The role of the specialist nurse is implicated. A larger scale study is necessary to elaborate this preliminary research.

Is the provision of information leaflets before colposcopy beneficial? A prospective randomised study.

OBJECTIVE: To assess the usefulness of a leaflet distributed to women before colposcopy designed to reduce their anxiety and psychosexual morbidity by providing information. DESIGN: Prospective randomised study. SETTING: Colposcopy clinic of a large district general hospital. SAMPLE: Two hundred consecutive women undergoing colposcopy for the first time for a cervical cytological abnormality of severity no greater than moderate dyskaryosis. METHODS: Women were randomised into one of two groups (leaflet or control). Those in the leaflet group were sent an information leaflet prior to attending the clinic. In the colposcopy clinic all the women completed a State/Trait Anxiety Inventory (StAI/TrAI) and a modified psychosexual questionnaire before undergoing colposcopy. This was repeated at the six-month follow up visit. Women in the leaflet group also completed a further questionnaire on the leaflet. MAIN OUTCOME MEASURES: Differences of anxiety and psychosexual scores between leaflet and control groups. RESULTS: The leaflet was well received. There were no statistical differences in StAI and TrAI scores between the study group and the control group at either visit, although in the whole study population StAI and TrAI scores were reduced at the second visit. The leaflet group had significantly more psychosexual problems but by the second visit, the scores had improved and the two groups were similar. When the mean differences in anxiety and psychosexual scores at the initial and second visits were compared between the groups, the reduction in negative sexual feelings and deterioration of TrAI scores experienced by the leaflet group was significant. CONCLUSIONS: This study suggests that the provision of sending an information leaflet prior to colposcopy is not beneficial in isolation. Other approaches need to be considered.

The experience of long-term hospital follow-up for women who have suffered early stage gynecological cancer: a qualitative interview study.

Bradley EJ, Pitts MK, Redman CWE, Calvert E. The experience of long term hospital follow-up for women who have suffered early stage gynecological cancer: a qualitative interview study. The objective of this paper is to investigate the factors involved in the wish for continuing long-term follow-up for early stage gynecological cancer in the absence of obvious clinical benefit. This qualitative study is comprised of semistructured, individual interviews. Twelve women who had been treated for early stage (I-II) gynecological cancer (cervical, vulval, ovarian, endometrial) and had been attending regular follow-up appointments at the hospital clinic for a minimum of six months were interviewed for this study. The primary outcome measures were women's views on their follow-up needs. Women who continue to express a need for follow-up appointments years after the treatment of active disease are seeking to alleviate anxiety regarding possible recurrent illness. The main element of follow-up that alleviates this recurrence anxiety is medical reassurance, this is only judged to be worthwhile when given by a gynecological consultant. There is a difficulty with regarding the period of remission as a healthy state, both cultural "lay" beliefs and family support exacerbate this difficulty. Although family support is deemed important initially, it may actually serve to maintain "sickness" identity, perpetuating views of cancer remission as another stage of illness. We conclude that the processes involved in follow-up for cancers with a very low recurrence risk are complex. Follow-up information is perhaps medical, but women who have a continued need for follow-up in the absence of any clinical disease are attending for psychological purposes. Further research is needed to study possible interventions that could be introduced to help alleviate anxiety during the period of cancer recovery.

Audit of the views of gynaecological cancer patients regarding follow-up.

The purpose of this study was to audit patients opinions on routine follow-up and discharge from the gynaecology clinic. The setting was the gynaecology clinic of a large district general hospital and the design was a cross-sectional audit analysis using a written questionnaire. The subjects were 103 women attending the gynaecological out patients for review following previous treatment for various gynaecological cancers. Ninety patients took part in the study, of these 36 (40%) wished for 'free access', 29 (32%) wished for routine hospital follow-up, and 25 (28%) wished for discharge but with follow-up by their general practitioner. There were no statistically significant differences in choices between cancer groups. The choice of 'free access'seemed to be an important choice for women. We conclude that routine hospital follow-up of women treated for gynaecological cancer is not the desire of the majority and it appears the women may have different inherent psychological characteristics.

Information, compliance and side-effects: a study of patients on antidepressant medication.

A study was carried out to elucidate whether the improved compliance associated with the provision of verbal and written information about a prescribed drug is due to the specific information or to a non-specific attention-placebo effect. 120 depressed outpatients were prescribed dothiepin and randomly allocated to one of three groups: Group A were given verbal and written information about side-effects; Group B were given verbal and written information about beneficial effects; Group C were told only that the drug was being given to treat their depression and received no written information. Compliance with medication was assessed at 3 weeks and 6 weeks by interrogation and by pill count. At the same time, side-effects were enquired for and their occurrence or non-occurrence noted. No significant differences were found between the groups in the rates of compliance at either 3 weeks or 6 weeks. When Groups A and B were combined to give a total 'information' group and compared with Group C--the 'no-information' group--the rate of compliance at 3 weeks was significantly higher (P less than 0.05) in the 'information' group. No significant differences were found between the groups in the rates of reported side-effects at either 3 weeks or 6 weeks. When Groups A and C were combined and compared with Group B (information about beneficial effects), side-effects were found to be reported significantly less frequently (P less than 0.05) in the latter at 6 weeks. Of 175 compliance estimates, 97.7% gave concordant results for estimation by interrogation and by pill count.(ABSTRACT TRUNCATED AT 250 WORDS)

Patterns of attendance at developmental assessment clinics.

A random sample of 489 children was collected at birth. There were clinic records for only 356 (73 per cent) of these children, and from this number 30 left the district or died. The parents of those with record cards were invited to bring their children to clinic when they reached the age of four years. Only 152 children (47 per cent) attended. Of the non-attenders, 129 were traced to schools in the borough when they reached the age of five years, as were 67 (51 per cent) of the 133 children without record cards. The children seen only at school were compared with the children seen at a Local Authority developmental assessment clinic. The clinic group were judged to come from the higher social classes and to have higher IQs than the school group, which suggests that clinics may be catering for those whose need is least.

An analysis of verbal-performance intelligence quotient discrepancies in the Wechsler Adult Intelligence Scale results of mentally subnormal hospital patients.

Verbal-Performance IQ discrepancies on the WAIS have been of much interest to clinical psychologists. They have been related, amongst other things, to different types of brain damage and in studies of the mentally subnormal, to successful adjustment to the outside world. This paper looks more closely at such discrepancies obtained by patients in a hospital for the mentally subnormal. These discrepancies are found to be both frequent related to Full Scale IQ. The pattern that emerges remains constant if scaled scores are considered or if the subtests are re-arranged according to Cohen's A and B factors. It is argued that these findings imply caution in the use of the discrepancy measure as a diagnostic or predictive indicator in this population.

The effect of forewarning on the occurrence of side-effects and discontinuance of medication in patients on dothiepin.

Dothiepin was prescribed for 100 depressed out-patients alternately allocated to one of two groups. Patients in Group A were forewarned about side-effects and patients in Group B were not forewarned. None of the patients had previously received dothiepin. After two weeks the patients were questioned regarding side-effects and continuance with medication. Eighty-nine patients were included in the final analysis. The results failed to confirm the hypotheses that forewarning patients of side-effects causes a greater number of patients to complain of such effects, or that where patients experience side-effects, forewarning is associated with any less frequent discontinuance of therapy. Compared with a previous study with amitriptyline, the results of this study are much closer to statistical significance. This may be due to the lower overall incidence of side-effects with dothiepin and calls for further work with a larger sample of patients.