Variable alterations of the microbiota, without metabolic or immunological change, following faecal microbiota transplantation in patients with chronic pouchitis.

Faecal microbiota transplantation (FMT) is effective in the treatment of Clostridium difficile infection, where efficacy correlates with changes in microbiota diversity and composition. The effects of FMT on recipient microbiota in inflammatory bowel diseases (IBD) remain unclear. We assessed the effects of FMT on microbiota composition and function, mucosal immune response, and clinical outcome in patients with chronic pouchitis. Eight patients with chronic pouchitis (current PDAI ≥7) were treated with FMT via nasogastric administration. Clinical activity was assessed before and four weeks following FMT. Faecal coliform antibiotic sensitivities were analysed, and changes in pouch faecal and mucosal microbiota assessed by 16S rRNA gene pyrosequencing and (1)H NMR spectroscopy. Lamina propria dendritic cell phenotype and cytokine profiles were assessed by flow cytometric analysis and multiplex assay. Following FMT, there were variable shifts in faecal and mucosal microbiota composition and, in some patients, changes in proportional abundance of species suggestive of a "healthier" pouch microbiota. However, there were no significant FMT-induced metabolic or immunological changes, or beneficial clinical response. Given the lack of clinical response following FMT via a single nasogastric administration our results suggest that FMT/bacteriotherapy for pouchitis patients requires further optimisation.

Exclusive elemental diet impacts on the gastrointestinal microbiota and improves symptoms in patients with chronic pouchitis.

BACKGROUND: Treatment resistant chronic pouchitis causes significant morbidity. Elemental diet is effective treatment for Crohn's disease. Since pouchitis shares some similarities to Crohn's disease we hypothesised that elemental diet may be an effective treatment. METHOD: Seven pouchitis patients (with ulcerative colitis) were studied. All had active pouchitis with a pouch disease activity index (PDAI) ≥7. Exclusion criteria were recent NSAIDs, antibiotics or probiotics. Sufficient elemental diet to achieve energy requirements was provided. Flexible-pouchoscopy was performed, and the Cleveland Global Quality of Life score (CGQoL), Pouch Disease Activity Index (PDAI) and BMI were recorded at baseline and following 28 days of elemental diet. Faecal samples were also collected at these time points and analysed for major bacterial groups using culture independent fluorescence in situ hybridisation. Data were analysed using Wilcoxon's signed-rank test. RESULTS: Following 28 days of exclusive elemental diet, median stool frequency decreased from 12 to 6 per day (p=0.028), median clinical PDAI decreased from 4 to 1 (p=0.039). There was no significant difference in quality of life scores or PDAI before and following treatment. There was a trend towards an increase in the concentration of Clostridium coccoides-Eubacterium rectale (median 7.9 to 8.5 log10/g, p=0.08) following exclusive elemental diet. CONCLUSION: Treatment with four weeks elemental diet appeared to improve the symptoms of chronic pouchitis in some patients but is not an effective strategy for inducing remission. Although a potential symptom modifier, elemental diet cannot be recommended for the routine treatment of active pouchitis.

Etiology of pouchitis.

Restorative proctocolectomy with ileal-pouch anal anastomosis (RPC) is the operation of choice for ulcerative colitis (UC) patients requiring surgery. It is also used for patients with familial adenomatous polyposis (FAP). Pouchitis accounts for 10% of pouch failures. It is an idiopathic inflammatory condition that may occur in up to 50% of patients after RPC for UC. It is rarely seen in FAP patients after RPC. The etiology of pouchitis remains unclear. An overlap with UC is suggested by the frequency with which pouchitis affects patients with UC compared with FAP patients. There is significant clinical evidence implicating bacteria in the pathogenesis of pouchitis. Studies using culture and molecular methods demonstrate a dysbiosis of the pouch microbiota in pouchitis. Risk factors, genetic associations, and serological markers of pouchitis suggest that the interactions between the host immune responses and the pouch microbiota underlie the etiology of this idiopathic inflammatory condition. Here we present a detailed review of the data focusing on the pouch microbiota and the immune responses that support this hypothesis. We also discuss the contribution of luminal metabolic factors and the epithelial membrane in the etiology of this inflammatory process. The ileoanal pouch offers a unique opportunity to study the inter-relationships between the gut microbiota and host immune responses from before the onset of disease. For this reason the study of pouchitis could serve as a human model that significantly enhances our understanding of inflammatory bowel diseases in general.

Review article: faecal transplantation therapy for gastrointestinal disease.

BACKGROUND: Evidence is emerging regarding the relationship between a dysbiosis of the human gut microbiota and a number of gastrointestinal diseases as well as diseases beyond the gut. Probiotics have been investigated in many gastrointestinal disease states, with variable and often modest outcomes. Faecal transplantation is an alternative approach to manipulate the gut microbiota. AIM: To review the use of faecal transplantation therapy for the management of gastrointestinal disorders. METHODS: Available articles on faecal transplantation in the management of gastrointestinal disorders were identified using a Pubmed search and bibliographies of review articles on the subject were collated. RESULTS: A total of 239 patients who had undergone faecal transplantation were reported. Seventeen of 22 studies of faecal transplantation were in fulminant or refractory Clostridium difficile. Studies of faecal transplantation are heterogeneous regarding the patients, donors, screening, methods of administration and definition of response. Faecal transplantation for C. difficile has been demonstrated to be effective in 145/166 (87%) patients. Small numbers of patients are reported to have undergone successful faecal transplantation for irritable bowel syndrome and inflammatory bowel disease. CONCLUSIONS: Faecal transplantation has been reported with good outcomes for fulminant and refractory C. difficile. No adverse effects of faecal transplantation have been reported. However, there are no level 1 data of faecal transplantation and reports to date may suffer from reporting bias of positive outcomes and under-reporting of adverse effects. This therapy holds great promise, where a dysbiosis of the gut microbiota is responsible for disease and further studies are necessary to explore this potential.

An open study of maintenance antibiotic therapy for chronic antibiotic-dependent pouchitis: efficacy, complications and outcome.

AIM: About 5% of restorative proctocolectomy (RPC) patients develop chronic antibiotic-dependent pouchitis. These require antibiotic maintenance therapy. We report our experience in managing this patient group. METHOD: Patients with RPC that was treated with antibiotic maintenance therapy were identified from the hospital pouch database. Data including faecal antibiotic sensitivity, functional outcome, side effects and Cleveland Global Quality of Life (CGQOL) score were recorded. RESULTS: Twenty-five patients were identified. The median length of treatment was 15.8 (range 3-62) months. Ten (40%) patients had pouchitis with co-existing prepouch ileitis. The median frequency of defecation was 7 (range 4-11)/24 h, the median clinical Pouch Disease Activity Index (PDAI) was 0 (range 0-1) and the CQGOL score was 0.7 (range 0.5-1.0). Of those who relapsed, three (50%) patients had achieved mucosal healing following the induction of remission. Failure of mucosal healing did not predict a reduced time to relapse (P = 0.18). Prepouch ileitis was associated with an increased risk of developing antibiotic resistance (P = 0.023). Treatment of this with alternating antibiotic combination therapy was successful in all cases. CONCLUSION: Antibiotic maintenance therapy appears safe, well-tolerated and effective for the treatment of chronic antibiotic-dependent pouchitis. It results in an improved quality of life and function. Prepouch ileitis, but not failure of mucosal healing, is associated with an increased risk of developing antibiotic resistance.

The bacterial pathogenesis and treatment of pouchitis.

Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis is the operation of choice for patients with ulcerative colitis. Pouchitis is the most common cause of pouch dysfunction. Although the pathogenesis of this disease is not well understood, bacteria have been implicated in the disease process. Numerous bacterial studies have been reported over the last 25 years with few unifying findings. In addition, many different treatments for pouchitis have been reported with varying results. Antibiotic treatment remains the most studied and is the mainstay of treatment. In this article we review the aetiology of pouchitis and the evidenced-based treatment options.

Extended spectrum beta-lactamase-producing bacteria and Clostridium difficile in patients with pouchitis.

BACKGROUND: Treatment with fluoroquinolones is associated with the development of Clostridium difficile and extended spectrum beta-lactamase-producing bacteria (ESBL). Clostridium difficile and ESBL are resistant to many antibiotics and each may cause pouchitis after restorative proctocolectomy (RPC) refractory to empirical antibiotic therapy. AIM: To assess the prevalence and establish risk factors for the development of ESBL and Clostridium difficile toxins (CDT) in RPC patients with recurrent or refractory pouchitis under follow-up at our institution over a 1-year period. METHOD: An enzyme-linked immunosorbent assay was used to detect CDT and a culture technique was used to identity ESBL in faecal samples. All patients had previously received fluoroquinolone treatment. RESULTS: Forty-eight patients (35 (74%) men; median age 42 years) underwent testing at a median interval from RPC of 8 (range 1-25) years. No patient had a positive CDT result, but ESBL bacteria were identified in 16 (33%) samples. ESBL positivity was significantly related to prepouch ileitis (P = 0.035) and maintenance antibiotic therapy (P = 0.039). CONCLUSIONS: Extended spectrum beta-lactamase, but not CDT, is a common finding in faecal samples from patients with recurrent or refractory pouchitis. Treatment with maintenance antibiotics and prepouch ileitis are risk factors for developing ESBL-producing bacteria.

A blinded pilot comparison of capsule endoscopy and small bowel histology in unresponsive celiac disease.

This study compares video capsule endoscopy (VCE) with histological specimens of proximal small bowel in patients with celiac disease who have failed to respond to a gluten-free diet. Patients with nonresponsive celiac disease underwent capsule endoscopy, and concordance between endoscopy and histology was then calculated using the kappa statistic. In 19 patients, endoscopy videos were reported as normal in ten (53%) case, as having mild changes in three (16%) cases, and as having moderate-severe changes in six (31%) cases. Two (11%) had acute ulcers. No small bowel tumors were seen. Endoscopy demonstrated concordance with histological changes in 14 of the 18 patients with histology available (78% concordance). The kappa statistic suggested a substantial degree of concordance between histology and endoscopic findings. Endoscopy with distal duodenal biopsies is superior to VCE in detecting proximal, nonresponsive celiac disease, but more distal lesions may be missed such that the strength of VCE lies in its ability to visualize the entire small bowel.

An open study of antibiotics for the treatment of pre-pouch ileitis following restorative proctocolectomy with ileal pouch-anal anastomosis.

BACKGROUND: Pre-pouch ileitis is a recently described condition which may occur following restorative proctocolectomy. Its aetiology remains unknown and only one study has reported the effect of treatment. We report a series of fourteen patients treated and followed up with repeat pouchoscopy. AIM: To study the effectiveness of antibiotics for the treatment of pre-pouch ileitis following restorative proctocolectomy with ileal pouch-anal anastomosis. METHODS: Fourteen consecutive patients with symptomatic pre-pouch ileitis were treated with ciprofloxacin 500 mg b.d. and metronidazole 400 mg b.d. for 28 days. All had concurrent pouchitis. Symptomatic, endoscopic and histological assessment was performed before and following treatment using the pouchitis disease activity index (PDAI). Symptomatic remission was defined as a score of 0 in the clinical component of the PDAI. RESULTS: Twelve (86%) patients experienced symptomatic remission. Stool frequency fell from a median of 12 (range 8-20) to 6 (4-17) (P = 0.002). There was a significant reduction in the anatomical length of pre-pouch ileitis with nine (64%) patients having either a resolution or a reduction in length of pre-pouch ileitis from a median of 10 cm (range 3-20 cm) to a median of 1 cm (range 0-10 cm) (P = 0.007). CONCLUSION: Combination antibiotic therapy in this uncontrolled study appears effective in reducing the length of pre-pouch ileitis and in inducing symptomatic remission in most patients whether or not its extent is reduced.

Review article: restorative proctocolectomy, indications, management of complications and follow-up--a guide for gastroenterologists.

BACKGROUND: Restorative proctocolectomy with ileal pouch-anal anastomosis is the procedure of choice for the majority of patients with ulcerative colitis who require surgery. Over 2500 patients in the UK have undergone restorative proctocolectomy. It is now increasingly being performed in district general hospitals as well as in specialist inflammatory bowel disease units. Gastroenterologists are increasingly involved in the management of patients following restorative proctocolectomy. AIM: To provide gastroenterologists with a clear understanding of the investigation and evidence-based management of complications and the aftercare required in patients who have undergone restorative proctocolectomy. RESULTS: Following restorative proctocolectomy, most patients have an excellent long-term functional outcome. Pouchitis, pelvic sepsis and poor function are the most common causes of failure. The development of cancer is rare; nevertheless, long-term follow-up is required. CONCLUSIONS: The investigation and management of patients who develop complications require a multidisciplinary team approach to optimize the outcome. Protocols are suggested for investigation and management of patients with complications and for long-term cancer surveillance.

Gender-related differences in the characteristics of problem gamblers using a gambling helpline.

OBJECTIVE: The characteristics of male and female gamblers utilizing a gambling helpline were examined to identify gender-related differences. METHOD: The authors performed logistic regression analyses on data obtained in 1998-1999 from callers to a gambling helpline serving southern New England. RESULTS: Of the 562 phone calls used in the analyses, 349 (62.1%) were from male callers and 213 (37.9%) from female callers. Gender-related differences were observed in reported patterns of gambling, gambling-related problems, borrowing and indebtedness, legal problems, suicidality, and treatment for mental health and gambling problems. Male gamblers were more likely than female gamblers to report problems with strategic or "face-to-face" forms of gambling, e.g., blackjack or poker. Female gamblers were more likely to report problems with nonstrategic, less interpersonally interactive forms of gambling, e.g., slot machines or bingo. Female gamblers were more likely to report receiving nongambling-related mental health treatment. Male gamblers were more likely to report a drug problem or an arrest related to gambling. High rates of debt and psychiatric symptoms related to gambling, including anxiety and depression, were observed in both groups. CONCLUSIONS: Individuals with gambling disorders have gender-related differences in underlying motivations to gamble and in problems generated by excessive gambling. Different strategies may be necessary to maximize treatment efficacy for men and for women with gambling problems.

Illegal behaviors in problem gambling: analysis of data from a gambling helpline.

Problem gambling behaviors, particularly the most severe form, which is pathological gambling (PG), represent an emerging public health problem. Compared with the general population, individuals with problem gambling are more likely to have reports of legal issues, including commission of crimes, arrest, and incarceration. The goal of the present study is to examine the characteristics of individuals seeking help for gambling problems with regard to reports of illegal behavior secondary to gambling. Individuals with gambling problems were identified through use of a 24-hour gambling helpline, and information regarding the identified problem gambler was investigated with respect to reported presence or absence of gambling-related illegal behaviors. Identified gamblers with reported gambling-related illegal behaviors compared with those without such behaviors appeared to experience more severe gambling-related problems. Despite being on average younger, gamblers with acknowledged gambling-related illegal behaviors were more likely to have reports of having problems with multiple forms of gambling, debts to acquaintances, been suicidal secondary to gambling, used alcohol or drugs excessively, and received mental health treatment. Secondary analyses of the subgroup of gamblers with gambling-related illegal behaviors revealed that those with reports of arrest or incarceration secondary to gambling compared with those with gambling-related illegal behaviors but without arrest or incarceration secondary to gambling were more likely to have features similar to those described for individuals with antisocial personality disorder (ASPD). That is, the gambler with reported arrest or incarceration secondary to gambling was more likely to be male, unemployed, single, and have reports of problems with excessive drug or alcohol use. In contrast, the gamblers acknowledging gambling-related illegal behaviors but not arrest or incarceration secondary to gambling were predominantly female and more likely to have reports of problems with non-strategic forms of gambling (e.g., slot machine), owing money to legitimate sources of borrowing, having filed for bankruptcy, and having family problems related to gambling. The findings indicate: (1) individuals with reported legal problems secondary to gambling represent a more ill subpopulation of problem gamblers; and (2) there exist separate subgroups of gamblers with gambling-related illegal behaviors (i.e., those with or without reported arrest or incarceration secondary to gambling) with strikingly different characteristics and possibly different treatment needs. The results of the present study highlight the importance of the identification and treatment of individuals with gambling problems with respect to legal issues.

Studies of whole blood associated acetaldehyde as a marker for alcohol intake: effect of gender in mice.

A study was undertaken in C57BL mice to evaluate the effect of gender on whole blood associated acetaldehyde following exposure to ethanol in the drinking water (10% v/v). Whole blood associated acetaldehyde (WBAA) was measured from capillary blood samples using a fluorigenic high performance chromatographic assay on days 0, 7, 15 and 27. Ethanol consumption did not impair growth of either male or female mice when compared to controls. Following administration of ethanol, WBAA increased in both male and female mice but marked gender differences were apparent. Female mice consumed more fluid relative to body weight than males (155 +/- 27 S.D. vs. 124 +/- 19 ml/kg/day, p less than 0.001), but had lower mean WBAA levels during the four weeks of ethanol administration (137 +/- 37 vs. 318 +/- 66 nmol/g hemoglobin, p less than 0.001). WBAA levels in male mice were stable over the course of the experiment. Female mice were found to have peak WBAA levels on day seven after which time levels decreased significantly. These experiments emphasize gender differences in ethanol metabolism as well as the need to establish norms based on gender for assays of ethanol consumption which use acetaldehyde adducts with blood proteins.

The effect of cigarette smoking on breath and whole blood-associated acetaldehyde.

Six pairs (1 habitual smoker and 1 nonsmoking control) of volunteers were studied to determine the effect of smoking tobacco on breath and whole blood acetaldehyde levels. On a given study day, samples of blood and breath were obtained from both participants at -0.25, 0, 0.25, 0.50, 0.75, 1.5, 2.5, and 3.5 hour time points. The smoking volunteer was told to smoke 1-3 cigarettes between the 0 and 0.25 hour time points. Acetaldehyde levels in breath and whole blood were quantified with a fluorigenic high performance liquid chromatographic assay. Acetaldehyde in breath rose six-fold in smokers at the 0.25 hour time point and returned to levels not significantly different from baseline values found in smokers or nonsmokers by 0.50 hr. Whole blood-associated acetaldehyde measurements remained unchanged in smokers throughout the experiment and were not different from nonsmokers. In conclusion, while smoking produces appreciable levels of acetaldehyde in expired air, the partitioning of acetaldehyde associated with smoking to blood or blood proteins appears to be below the level of detection of the assay employed (picomolar). Smoking of tobacco products may not interfere with assays designed to quantify ethanol intake by measuring acetaldehyde adducts with blood proteins.

Recent changes in mortality and labor force behavior among older Americans: consequences for nonworking life expectancy.

Increment-decrement working life tables for 1972 and 1980 are used to assess the relative impact of recent changes in mortality and labor force behavior on the number of years older men and women can expect to spend out of the labor force (nonworking life expectancy). The life tables are based on data from the Current Population Surveys and pertain to the population aged 55 and older for the two observation points. The results indicate that nonworking life expectancy increased dramatically between 1972 and 1980 for both men and women. Although labor force behavior changed markedly for both population groups during the observation period, the results clearly identify that changes in mortality were responsible for the increases in nonworking life expectancy. Implications of the findings for social policy are briefly discussed.

Changes in the retirement process among older men in the United States: 1972-1980.

Recent changes in older men's retirement patterns are investigated for the United States. The results show that labor force incumbents, particularly those in secondary occupations, experienced increases in the volume of both retirement and reentry to the labor force. In addition, although working life expectancy remained relatively stable across occupations, men in secondary occupations spent increasingly greater portions of their work lives in postretirement jobs. Finally, large increases in nonworking life expectancy occurred because of substantial increases in life expectancy. In several occupations, however, declines in working life expectancy were major contributors to increases in nonworking life expectancy.

Do adolescents who relinquish their children fare better or worse than those who raise them?

When background and other characteristics are controlled for, older adolescents who rear their children are as likely as those who place them for adoption to complete high school. However, relinquishers are more likely to complete vocational training and have higher educational aspirations. Further, relinquishers are more likely to delay marriage, to be employed six and 12 months after the birth and to live in higher income households than are child rearers. Child rearers are more likely to become pregnant again sooner and to resolve subsequent pregnancies by abortion. Adolescents who relinquish their children do not suffer more negative psychological consequences than do those who raise their children. Overall, both groups indicated very high levels of satisfaction with their decision to relinquish or to rear, although relinquishers were slightly less satisfied with their decision than were child rearers. The study sample consisted of 123 child rearers and 146 relinquishers who had attended a pregnancy-counseling program affiliated with a large adoption agency that practices open adoption. Hence, the findings are limited to a select sample and should not be generalized beyond adolescents who participate in a similar program.

The effect of marital status at first birth on marital dissolution among adolescent mothers.

The sequencing of marriage and first birth was expected to play an important role in the stability of marriage among adolescent mothers. We hypothesized that adolescent women who married prior to conception would have the lowest rates of marital disruption, followed by those who married between conception and birth. Adolescent women who gave birth prior to marriage were expected to suffer the highest rates of marital dissolution. The results provide partial support for our hypotheses. There is little difference in the probability of separation between adolescent mothers who had a postmarital conception and those who had a premarital conception but married before the birth. Having a premarital birth, however, significantly increases the probability of marital dissolution. We also hypothesized that marital status at first birth would have less effect on the probability of marital dissolution for blacks than for whites. This, too, is generally supported by our findings. Among black females, those with a premarital birth are the first to suffer a marital disruption, but by the end of ten years there is little difference in the probability of separation among the three marital status groups. In contrast, among white females, those with a premarital birth are the first to experience a disruption, and this differential persists over all subsequent marriage duration intervals. Thus, the sequencing of marriage relative to birth has similar short term effects for whites and blacks, but the effect for blacks is evident only in the short term. Ten years after the marriage, black adolescent mothers have similar rates of marital stability regardless of the sequencing of marriage. This is consistent with the findings of previous research and with our hypothesis; with the black family pattern of lower rates of marriage, higher rates of illegitimacy and higher divorce rates, the sequencing of marriage has no long lasting consequences on marital stability. Finally, our predicted decline in the effect of marital status at first birth over historical time also finds partial support. For white females there has been a change in the effect of marriage-first birth sequencing on separation over time. In the period encompassed by the women in our study, white adolescent mothers who married subsequent to the birth have been the most likely to experience a separation at all marriage duration intervals, but this differential narrows as age at interview declines. Among black females there has been no change in the effect of a premarital birth over time.(ABSTRACT TRUNCATED AT 400 WORDS)