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Crohns disease and ulcerative colitis are the two principal forms of inflammatory bowel disease (IBD). The root causes of these chronic and acute immunological disorders are unclear, but intestinal microorganisms are known to play a key role in the initiation and maintenance of disease. However, at present, there is no clear evidence for a single transmissible agent being involved in IBD aetiology. Although marked alterations occur in faecal and mucosal bacterial communities in IBD, it is unclear whether they are responsible for causing disease, or are due to changes in the gut environment that result from inflammatory reactions and extensive tissue destruction. Despite the involvement of microorganisms in inflammatory processes, antibiotic therapy has generally been unsuccessful in IBD. However, recent studies involving the use of probiotics, prebiotics and synbiotics suggest that there is potential for controlling these diseases through manipulation of the composition of the gut microbiota, and direct interactions with the gut immune system.

The article quantifies the effects of the impact of the bottom proximity on the heave added mass and hydrodynamic damping of a 6-meter diameter suction can. The study conducted decay tests at several heave frequencies while determining heave added mass and damping. It also investigated clearances of the model from the sea floor at various can heights. Results demonstrated that heave added mass and damping increase as the suction cans approaches the sea floor while hydrodynamic damping also increased moderately as the under bottom clearance reduced.

AbstractThis paper reports on an investigation into the influence of a pre-existing wave environment on ship motion experiments. A method is presented that enables appropriate wave thresholds to be set to ensure consistent, accurate and repeatable results, while minimising waiting time between runs. In addition, the optimal use of a wave dissipation device (or side beach) has been examined to maximise the productivity of the tank by minimising the time between runs. A system has been developed to continuously monitor the water stilling in the towing tank during the time period between runs. The software, written in LabVIEW, provides the towing tank operator with a signal when it is appropriate to commence the next test run. The use of the proposed method and analysis system was examined through a series of monohull head sea tests. It was found that total waiting times between runs may be reduced from the current practice of 10 to 20 minutes to an optimum of approximately 5 minutes without compromising accuracy.

OBJECTIVE: To establish the aetiological influences of persistent neck pain following a motor vehicle collision and to construct a model for use in the emergency department for identifying patients at high risk of persistent symptoms. DESIGN: Prospective cohort study. Patients recruited from hospital emergency departments were sent a questionnaire to gather information on various exposures. They were followed up at 1, 3, and 12 months to identify those with persistent symptoms. MAIN OUTCOME MEASURE: Persistent neck pain (pain at 1, 3, and 12 months after collision). RESULTS: The baseline survey included 765 patients. Subsequently, 480 completed a questionnaire at each follow up time point, of whom 128 (27%) reported neck pain on each occasion. Few collision specific factors predicted persistent neck pain. In contrast, a high level of general psychological distress, pre-collision history of widespread body pain, type of vehicle, whiplash associated symptoms, and initial neck disability best predicted the persistence of symptoms. Furthermore, these factors, in combination, accounted for more than a fivefold increase in the risk of persistent neck pain. CONCLUSION: The greatest predictors of persistent neck pain following a motor vehicle collision relate to psychological distress and aspects of pre-collision health rather than to various attributes of the collision itself. With these factors, and those relating to initial injury severity, it is possible to identify a subgroup of patients presenting with neck pain with the highest risk of persistent symptoms. Thus, it is possible to identify whiplash patients with a poor prognosis and to provide closer follow up and specific attention to management in these individuals.

Objective. To test the hypothesis that the prevalence of specific musculoskeletal pain symptoms has increased over time in the northwest region of England. To meet this objective we have examined the difference in the prevalence of low back, shoulder and widespread pain between the 1950s and today using historical data collected by the Arthritis Research Campaign (arc).Methods. Two cross-sectional surveys conducted over 40 yr apart in the northwest region of England. The status of two regional pain sites and widespread pain was determined using interview and questionnaire responses, for the earlier and later studies respectively. Subjects were classified positively if they reported low back pain, shoulder pain or widespread pain on the day of the survey. Rates were standardized to the Greater Manchester population.Results. There were large differences in the prevalence of musculoskeletal pain between the two surveys. For all three symptoms examined prevalence increased from 2- to 4-fold between the two surveys. In both surveys low back pain was more common in women. Shoulder and widespread pain was less prevalent in women than in men in the earlier survey but by the time of the later survey women reported more pain at these sites.Conclusions. The prevalence of musculoskeletal pain is much higher than that reported over 40 yr ago. The change in prevalence is unlikely to be entirely due to the study design; other possible explanations such as the increased reporting or awareness of these symptoms is discussed.

This article summarizes the work of the Arthritis Research Campaign Epidemiology Unit in the field of pain and soft tissue rheumatism during the 50 years 1954–2004. It reviews the information gathered on the occurrence of symptoms and its causes, which began with Kellgren and Lawrence's pioneering work during the 1950s in the coalfields and general population of Leigh, Greater Manchester. They studied the roles of posture, mechanical load and the physical environment (dampness) on back pain. This was followed by the Calderdale study in the 1980s examining the prevalence of disability and its causes in the population, which demonstrated the important role of regional pain in causing disability. More recent studies in the 1990s and at the beginning of the 21st century have allowed us to define the relative roles of mechanical (load) factors, individual (psychological) factors and the social environment, and the biological mechanisms by which they may result in symptoms. The further challenge over the coming decade is to use our knowledge of the aetiology and influences on outcome to design management strategies which demonstrate improved outcomes for patients.

Objectives. The relationship between hip pain and radiographic change in the population is unclear due to lack of agreed definition for hip pain and difficulties in obtaining radiographs from asymptomatic random samples. Our objective was to assess the relationship between hip pain and radiographic change in osteoarthritis (OA) in a population sample aged over 45.Methods. One thousand and seventy-one responders to a postal questionnaire using a recently validated approach to defining hip pain were stratified into hip pain-positive and -negative groups and samples of each were X-rayed and scored for OA using both minimum joint space and the Croft score. The association between pain and X-ray score was estimated, weighting back to the age and gender distribution of the original population.Results. Hip pain prevalence was 7% in males and 10% in females. Severe OA was present in 16% of those with and 3% of those without pain. Adjusting for age and gender, there was a very strong association of pain with severe OA [odds ratio (OR) 17.4, 95% confidence interval (CI) 3.0–102], but no association with mild/moderate OA (OR 1.4, 95% CI 0.4–4.7). By contrast, only 22% of men aged 45–54 with severe OA had current pain, though in older age groups the proportions with pain were higher (54–70%).Conclusions. Hip pain is relatively infrequent in the general population compared with the published reports of other regional pain syndromes. Mild/moderate radiographic change is very frequent and not related to pain, whereas severe change is rare but strongly related. In younger males, severe radiographic change is much less likely to be associated with pain.

Background. We have recently demonstrated that individual psychosocial factors are important predictors of the onset of chronic widespread pain. It has been hypothesized that excessive mechanical exposure may also be associated with symptom onset, although this has not been formally examined. We therefore determined the relative contributions of individual psychosocial and work-related mechanical, posture and environment factors in symptom onset.
Methods. We conducted a population-based prospective survey and identified 1658 adults aged 18-65 yr who were symptom-free. At baseline, detailed information was obtained on work-related mechanical and environment factors using validated instruments. Individual psychosocial features were also measured. Subjects free of chronic widespread pain at baseline were followed up at 12 and 36 months to identify those reporting the onset of new symptoms.
Results. In all, 1445 (91%) returned the questionnaire at 12 months and 978 (89%) at 36 months. Of these, 81 and 92 respectively reported new chronic widespread pain. Symptom onset was predicted by workplace factors {pushing/pulling heavy weights [relative risk (RR) = 1.8, 95% confidence interval (CI) 1.1, 3.0]; repetitive movements of the wrists (RR = 1.8, 95% CI 1.2, 2.7); kneeling (RR = 2.2, 95% CI 1.2, 4.1)} and individual factors [aspects of illness behaviour (RR = 2.9, 95% CI 1.6, 5.3); somatic symptoms (RR = 1.9 95% CI 1.1, 3.3); fatigue (RR = 1.9, 95% CI 1.2, 3.1); baseline pain symptoms (RR = 2.5, 95% CI 1.6, 3.9)]. In multivariate analysis, pushing/pulling heavy weights, repetitive wrist movements, kneeling and other pain at baseline were associated with new-onset chronic widespread pain. However, the strongest predictor was a high score on the illness behaviour scale.
Conclusion. This study provides only limited support for the hypothesis that low-level mechanical injury may be a risk factor for developing chronic widespread pain. The onset of chronic widespread pain appears to be multifactorial and is strongly predicted by individual psychosocial factors.

OBJECTIVE: Clinic based studies suggest that adverse events in childhood may predispose to chronic pain in adult life. These have been conducted on highly selected groups, and it is unknown whether these relationships hold in the general population and to what extent the increased rate of adverse childhood events in persons with pain is an artefact of differential reporting. We examined the hypothesis that chronic widespread pain was associated with reports of adverse experiences in childhood and whether any observed relationships could be explained by differential recall. METHODS: A cross sectional population based screening survey was conducted. Subjects completed a questionnaire that included assessments of pain and psychological state. In total, 296 subjects who had demonstrated psychological distress were randomly selected and had a detailed interview, which included an assessment of 14 adverse childhood experiences. Medical records relating to childhood were also examined for those subjects. RESULTS: The prevalence of self-reported adverse childhood experiences was greatest in adult subjects with current chronic widespread pain. Exposure to illness in family members, parental loss, operations, and abuse were all associated with increased, but nonsignificant, odds of having chronic widespread pain versus those without such exposures. However the only statistically significant association was with childhood hospitalizations. From medical record information the associations of hospitalizations (OR 5.1, 95% CI 2.0-13.0) and operations (OR 3.0, 95% CI 1.2-7.2) with pain previously noted were partly explained by differential recall between subjects with and without pain: hospitalizations, OR 2.2, 95% CI 0.9-5.5; operations, OR 1.2, 95% CI 0.5-3.4. CONCLUSION: Although several reported adverse events in childhood were observed to be associated with chronic widespread pain in adulthood, only reports of hospitalizations were significantly associated. Validation of self-reported exposures suggests that there was differential recall of past events among those with and without pain, and this differential recall explained the association between hospitalizations and current chronic pain. Such differential recall may explain other observations of an association between reports of adverse childhood events and chronic pain in adulthood.

OBJECTIVE: To determine the influence of short term work related psychosocial factors (work demands, job control, and social support) and psychological distress on regional pain syndromes. METHODS: Newly employed workers were recruited from 12 occupational groups and information collected by questionnaire. Subjects indicated on a blank body manikin any low back, shoulder, wrist/forearm, or knee pain that had occurred during the past month and lasted more than one day. Data were also collected on work related psychosocial factors and on levels of psychological distress [using the General Health Questionnaire (GHQ)]. The relationships between psychosocial factors and psychological distress and each area of pain were calculated as odds ratios with 95% confidence intervals. Adjustment was made for age, sex, and occupational group. RESULTS: 1081 subjects (median age 23; interquartile range 20-27) were recruited to the study shortly after commencing employment: 261 (24%) reported low back pain, 221 (20%) reported shoulder pain, 93 (9%) reported wrist/forearm pain, and 222 (21%) reported knee pain. High levels of psychological distress were associated with increased likelihood of pain, with a trend observed between scores on the GHQ and the odds of pain in each of the 4 sites. Those who perceived their work as stressful most of the time were more likely to report back (OR 1.8, 95% CI 1.01-3.1) or shoulder pain (OR 1.9, 95% CI 1.02-3.4) than those who considered their work seldom stressful. Pace of work or job autonomy was less markedly related to pain at individual sites. Strong relationships were observed between psychological distress, job demands (stressful work, hectic work), low job control, and pain at multiple sites. CONCLUSION: The study has shown that adverse work related psychosocial factors, in particular aspects of job demand and control, influence the reporting of regional musculoskeletal pain. This occurs even after only short term exposure. The odds of reporting these adverse exposures are increased when pain is reported at multiple sites.

Objectives. The primary objective was to test the hypothesis that new attenders in primary care with hip pain and radiographic osteoarthritis (OA) have a decreased range of movement compared with those without OA. The secondary objective was to define the planes of movement and thresholds that were the most discriminatory for OA.
Methods. Men and women aged 40 yr and over presenting with a new episode of hip pain were recruited from 36 general practices across the UK. A standardized radiographic and clinical examination was performed. The discriminating ability of the range of movement for each plane to identify those with radiographic OA was assessed using receiver operating characteristic curves.
Results. New hip pain attenders with radiographic OA had restricted movement at the hip compared with those without radiographic change. Restriction in internal rotation was the most predictive and flexion the least predictive of radiographic OA. At this cut-off, restriction in any single plane had a sensitivity of 86% for moderate and 100% for severe OA (specificity was 54 and 42% respectively). Restriction in all three planes had greater discrimination (sensitivity was 33% for mild to moderate OA and 54% for severe OA; specificity was 93 and 88% respectively).
Conclusions. Restriction in range of movement was predictive of the presence of OA in these new presenters to primary care with hip pain, and the results of this examination could be used to inform decisions regarding radiography.

BACKGROUND: The normal intestinal microflora plays an important role in host metabolism and provides a natural defence mechanism against invading pathogens. Although the microbiota in adults has been extensively studied, little is known of the changes that occur in the microflora with aging. These may have important consequences in elderly people, many of whom are receiving antibiotic therapy and who are most susceptible to intestinal dysbiosis. AIMS: To characterise the major groups of faecal bacteria in subjects of different ages using a combination of cultural, molecular, and chemotaxonomic approaches. METHODS: Comparative microbiological studies were made on four different subject groups: children (16 months to seven years, n=10), adults (21-34 years, n=7), healthy elderly subjects (67-88 years, n=5), and geriatric patients (68-73 years, n=4) diagnosed with Clostridium difficile diarrhoea. Selected faecal bacteria were investigated using viable counting procedures, 16S ribosomal RNA (rRNA) abundance measurements, and the occurrence of specific signature fatty acids in whole community fatty acid methyl ester profiles. RESULTS: The principal microbiological difference between adults and children was the occurrence of higher numbers of enterobacteria in the latter group, as determined by viable counts (p<0.05) and 16S rRNA (p<0.01) measurements. Moreover, a greater proportion of children's faecal rRNA was hybridised by the three probes (bifidobacteria, enterobacteria, bacteroides-porphyromonas-prevotella) used in the study, indicating a less developed gut microbiota. Species diversity was also markedly lower in the Clostridium difficile associated diarrhoea group, which was characterised by high numbers of facultative anaerobes and low levels of bifidobacteria and bacteroides. Although it was a considerably less sensitive diagnostic tool, cellular fatty acid analysis correlated with viable bacterial counts and 16S rRNA measurements in a number of bacteria, including bacteroides. CONCLUSIONS: Polyphasic analysis of faecal bacteria showed that significant structural changes occur in the microbiota with aging, and this was especially evident with respect to putatively protective bifidobacteria. Reductions in these organisms in the large bowel may be related to increased disease risk in elderly people.

This article describes a new, noninvasive method of assessing the severity of hallux valgus deformity by means of a set of standardized photographs. Six podiatrists were independently asked to grade the level of deformity of 13 subjects (26 feet) on a scale of 1 (no deformity) to 4 (severe deformity). The reliability of the four-point scale for the severity of hallux valgus was investigated by means of kappa-type statistics for more than two raters. The results showed that the grading method had excellent interobserver repeatability with a combined kappa-type statistic of 0.86, making it a suitable instrument for clinical and research purposes.

Background. Chronic widespread pain is the cardinal clinical feature of the fibromyalgia syndrome, which, in the majority of clinic patients, is persistent. By contrast, in community‐derived patients, pain is persistent in only half of the affected individuals, particularly those with psychological distress. Whether such distress is a consequence of the pain or a manifestation of a wider process of somatization which is associated with the persistence of pain is unclear.Objectives. We tested in a large, prospective, population‐based study the hypothesis that features of somatization predict the persistence of chronic widespread pain.Methods. In all, 252 (13%) of 1953 adult subjects selected from a population register were classified as having chronic widespread pain based on a detailed questionnaire which included a pain drawing. The patients also completed a number of psychosocial instruments which measure features known to be associated with somatization. Two hundred and twenty‐five (91%) of the patients were successfully followed up after 12 months and provided data on pain status using the same instruments.Results. In all, 126 (56%) patients reported chronic widespread pain at follow‐up, 74 (33%) reported other pain and 25 (11%) reported no pain. Persistent chronic widespread pain was strongly associated with baseline test scores for high psychological distress and fatigue. In addition, these subjects were more likely to display a pattern of illness behaviour characterized by frequent visits to medical practitioners for symptoms which disrupt daily activities. The prevalence of persistent pain increased with the number of risk factors the subjects were exposed to.Conclusions. Although almost half of the cases of chronic widespread pain resolved within 1 yr, this study has demonstrated for the first time that those subjects who display features of somatization are more likely to have widespread pain which persists. These findings have implications for the identification and treatment of persons with persistent chronic widespread pain.

OBJECTIVE: To determine the aetiology of forearm pain. In particular to determine the relative contribution of (a) psychological factors, features of somatisation, and health anxiety and behaviour, (b) work related mechanical factors, and (c) work related psychosocial factors in the onset of forearm pain. DESIGN: 2 year prospective population based cohort study, with retrospective assessment of exposures at work. SETTING: Altrincham, Greater Manchester. PARTICIPANTS: 1953 individuals aged 18-65 years. OUTCOME MEASURES: Forearm pain of new onset. RESULTS: At follow up, 105 (8.3%) participants reported forearm pain of new onset lasting at least one day in the past month. Among these, 67% also reported shoulder pain, 65% back pain, and 45% chronic widespread pain. Increased risks of onset were associated with high levels of psychological distress (relative risk 2.4, 95% confidence interval 1.5 to 3.8), reporting at least two other somatic symptoms (1.7, 0.95 to 3.0), and high scores on the illness behaviour subscale of the illness attitude scales. The two work related mechanical exposures associated with the highest risk of forearm pain in the future were repetitive movements of the arm (4.1, 1.7 to 10) or wrists (3.4, 1.3 to 8.7), whereas the strongest work related psychosocial risk was dissatisfaction with support from colleagues or supervisors (4.7, 2. 2 to 10). CONCLUSIONS: Psychological distress, aspects of illness behaviour, and other somatic symptoms are important predictors of onset of forearm pain in addition to work related psychosocial and mechanical factors. Misleading terms such as "cumulative trauma disorder" or "repetitive strain injury," implying a single uniform aetiology, should be avoided.

Objective. To determine the prevalence of radiographic osteoarthritis in subjects with hip pain newly presenting to primary care.
Methods. The study was cross-sectional in design, set in 35 general practices across the UK. It included 195 men and women aged 40 yr and over (median 63 yr) presenting with a new episode of hip pain. Hip radiographs were scored for minimum joint space (MJS) and overall--Croft's modification of the Kellgren and Lawrence (Croft)--grade of osteoarthritis.
Results. In all, definite evidence of radiographic change in the painful joint was common: Croft grade ≥ 2 in 44%, ≥ 3 in 34%. MJS of 2.5 mm or less was seen in 30% of whom half were below 1.5 mm. There were no significant gender differences in radiographic severity.
Conclusions. Radiographic change is common in patients newly presenting with hip pain and many already have advanced disease.

OBJECTIVES: To quantify the relative contribution of premorbid and episode specific factors in determining the long term persistence of disabling symptoms of low back pain. DESIGN: Prospective cohort study. SETTING: Two general practices in the south Manchester area. PARTICIPANTS: 180 patients, who previously participated in a cross sectional population survey, who consulted because of low back pain during the study period. They were followed at 1 week and 3 and 12 months after consultation. MAIN OUTCOME MEASURE: Persistent disabling low back pain in the 12 months after the consultation. RESULTS: Disabling low back pain persisted in one third of participants after consultation and was more common with increasing age, among those with a history of low back pain, and in women. Persistence of symptoms was associated with "premorbid" factors (high levels of psychological distress (odds ratio 3.3; 95% confidence interval 1.5 to 7.2), poor self rated health (3.6; 1.9 to 6.8), low levels of physical activity (2.8; 1.4 to 5.6), smoking (2. 1; 1.0 to 4.3), dissatisfaction with employment (2.4; 1.3 to 4.5)) and factors related to the episode of low back pain (duration of symptoms, pain radiating to the leg (2.6; 1.3 to 5.1), widespread pain (6.4; 2.7 to 15), and restriction in spinal mobility). A multivariate model based on six factors identified groups whose likelihood of persistent symptoms ranged from 6% to 70%. CONCLUSIONS: The presence of persistent low back pain is determined not only by clinical factors associated with pain but also by the premorbid state.

Clostridium septicumNCTC 282 was cytotoxic for CACO-2 and HEp-2 cells. However, HEp-2 cells were more resistant than CACO-2 cells toC. septicumcytotoxin. Short motile rod forms were considerably more cytotoxic than swarming bacteria. Bacterial adhesion only occurred with HEp-2, and short motile rod forms adhered in significantly greater numbers than swarming bacteria. Removal of bacterial flagella by mechanical shearing had little effect on adherence, demonstrating that these surface structures did not act as adhesins. Addition of a variety of monosaccharides (sucrose,D-fucose,L-fucose, mannose) to HEp-2 cell monolayers had little effect on bacterial adhesion, although maltose effected a 50% reduction. Invasion of HEp-2 cells byC. septicumoccurred with short motile rods, but not with swarming bacteria, suggesting that the initial stages of infection by this organism may be affected by the abilities of different cell forms to adhere to and invade epithelial cells. Since cytotoxicity, adherence and epithelial cell invasion byC. septicumis dependent on bacterial form, differentiation of the organism into swarm cells in response to environmental factors will influence the pathogenesis of infection.

Background:Several different types of in vitro fermentation systems are currently employed to investigate pro- and prebiotic activities in the human large intestinal microbiota, ranging from simple batch cultures, with or without stirring and pH control, to more complex models involving pH controlled single and multiple-component continuous culture systems. Methods:In this investigation, we used a three-stage continuous culture model to study the activities of colonic bacteria. This fermentation system reproduces several of the nutritional and environmental characteristics of the proximal large intestine (vessel 1) and the distal colon (vessels 2 and 3), and was validated using bacteriological, metabolic and chemical measurements made with intestinal material obtained from different regions of the large bowel. In this paper, we report studies on prospective probiotic effects of Bifidobacterium longumNCFB 2259 in relation to other bacterial populations, production of tyrosine and phenylalanine metabolites, and bacterial synthesis of enzymes involved in the formation of putatively genotoxic metabolites, including ß glucosidase (GS), arylsulphatase (AS), ß-glucuronidase (GN), nitroreductase (NR) and azoreductase (AR). Results:Bacterial activities at two different retention times were studied (31.1 and 68.4 h), which correspond to large intestinal transit times. At R = 31.4 h, significant probiotic effects were observed with respect to reductions in GS and GN, upon adding B. longum.However, despite the fact that this organism does not ferment aromatic amino acids or produce significant amounts of genotoxic enzymes, dysbiotic manifestations occurred in that both NR synthesis and dissimilatory tyrosine metabolism were stimulated. In contrast, at R = 68.4 h, GS formation increased between five and 20-fold, while GN and NR activities increased by a factor of two after adding the bifidobacterium. These data are reviewed in relation to potential health hazards that may be encountered with long-term probiotic administration. In the prebiotic experiments, the three-stage fermentation system was operated at R = 65 h. Oligofructose was added to VI to give an initial concentration of 30 grams per litre, when the system was in steady state, to study its effects on a number of experimental parameters including bifidogenicity, bacterial growth, fermentation product formation and mutagenicity. After addition of the oligosaccharide, a multiplicity of effects were observed in VI, where synthesis of NR and AR, bifidobacterial populations and overall fermentation processes were stimulated, although these influences progressively diminished in V2 and V3. Conclusions:These studies indicate that bacterial metabolism and putative beneficial consequences associated with the breakdown of readily fermentable prebiotics in the large intestine may in some circumstances be spatially and temporally limited to the proximal bowel.

In both health and disease, the colonic microbiota plays an important role in several areas of human physiology. This complex assemblage of microorganisms endows great metabolic potential on the large intestine, primarily through its degradative abilities. Many hundreds of different types of bacteria, varying widely in physiology and biochemistry, exist in a multitude of different microhabitats in the lumen of the large gut, the mucin layer and on mucosal surfaces. Both microbiota and host obtain clear benefits from association. For example, growth substrates from diet and body tissues, together with a relatively stable environment for bacteria to proliferate are provided by the host, which in turn has evolved to use butyrate, a bacterial fermentation product, as its principal source of energy for epithelial cells in the distal bowel. The main sources of carbon and energy for intestinal bacteria are complex carbohydrates (starches, non- starch polysaccharides). Carbohydrate metabolism is of great importance in the large intestine, since genetically, and in terms of absolute numbers, the vast majority of culturable microorganisms are saccharolytic. The amounts and types of fermentation products formed by colonic bacteria depend on the relative amounts of each substrate available, their chemical structures and compositions, as well as the fermentation strategies (biochemical characteristics and catabolite regulatory mechanisms) of bacteria participating in depolymerization and fermentation of the substrates. Protein breakdown and dissimilatory amino acid metabolism result in the formation of a number of putatively toxic metabolites, including phenols, indoles and amines. Production of these substances is inhibited or repressed in many intestinal microorganisms by a fermentable source of carbohydrate. Owing to the anatomy and physiology of the colon, putrefactive processes become quantitatively more important in the distal bowel, where carbohydrate is more limiting.

To assess current trends in male mortality from cancers of the oral cavity/pharynx, oesophagus, and larynx (upper aerodigestive tract cancers), and relate these to past national consumption of alcohol and smoking of cigarettes. To assess the impact of current trends in alcohol consumption and tobacco smoking on likely future rates of these cancers.

There have been recent reports of substantial increases occurring in the incidence of and/or mortality from tongue and mouth cancers in several countries. In this paper using data from Scotland (1960–89) we report on time trends in pharyngeal cancer. Similar increases in rates are evident for cancers of the oropharynx and hypopharynx while there has been little change in the occurrence of nasopharyngeal cancer (which has distinct aetiological factors). It therefore seems that reported changes in the incidence of and mortality from oral cancer may be real, and in Scotland, this is most probably due to changes in alcohol consumption.

This article reviews the epidemiology of cancer of the pancreas, both descriptive and analytical, at all times cognizant of the problems of misdiagnosis, particularly underdiagnosis, of this lethal disease that continue to hinder epidemiological studies. Pancreas cancer is consistently reported to occur more frequently in men than in women, in blacks than in whites, and in urban rather than rural population groups. In some countries, the mortality rates continue to rise, whereas in others, declining levels of disease can be seen among members of younger birth cohorts. Although some of these patterns can be explained by variation in pancreas cancer risk factors, many cannot. Analytical studies consistently demonstrate that cigaret smoking increases the risk of cancer of the pancreas, and this appears, at the present time, to be the only clearly demonstrated risk factor for pancreatic cancer. Although the association with disease risk and coffee consumption, alcohol consumption, occupational exposures, diabetes, pancreatitis, and other factors requires clarification, it appears likely that the most fruitful research area in the coming years may involve exploration of pancreatic cancer risk and nutritional practices.

Studies showed that the plant cell wall polysaccharide arabinogalactan supported growth of Bifidobacterium longum in batch culture. Galactose was also utilized, but not arabinose, the other major constituent sugar of the polymer. Enzymes required for hydrolysis of arabinogalactan ('arabinogalactanase', α-arabinopyranosidase, β-galactosidase) were inducible and cell-associated in B. longum, and their expression was repressed by glucose. Considerable amounts of α-arabinopyranosidase and β-galactosidase were synthesized during growth on arabinogalactan, but only low levels of arabinogalactanase were detected. B. longum only grew on arabinogalactan in continuous culture under putative carbon-excess conditions. In C-limited chemostats, the bifidobacterium could not establish unless Bacteroides thetaiotaomicron was present in co-culture. The relationship between the two organisms was not simply commensal; at low specific growth rates, bacteroides cell population densities were approximately 30% lower than those recorded in axenic culture, indicating the existence of competitive interactions with the bifidobacterium. In contrast, at high specific growth rates, a mutualistic association was observed, in that Bact. thetaiotaomicron was maintained in the chemostats at high dilution rates if bifidobacteria were also present. Measurements of residual carbohydrate in spent culture fluid from C-limited chemostats indicated that a large part of the arabinogalactan molecule could not be broken down by either B. longum or Bact. thetaiotaomicron alone, or in co-culture. Formate and acetate were the major fermentation products of B. longum cultured in the presence of high concentrations of arabinogalactan, confirming that these bacteria were growing under energy-limited conditions. Copyright 1995, 1999 Academic Press

The prevalence of urinary symptoms associated with benign prostatic hyperplasia was studied in a community-based, nationwide, representative sample of 2,011 French men 50 to 80 years old. Symptoms were assessed by the American Urological Association symptom index. After exclusion of patients with prostate cancer, 6.9% of the subjects reported having undergone prostate surgery. Among the surgery-free subjects, nocturia and repeat voiding within 2hours were the most prevalent symptoms. Based on the American Urological Association symptom index, 18.8% of the men were considered free of urinary symptoms, and 67%, 13% and 1.2%, respectively, ranked between 1 ánd 7, 8 and 19, and 20 or more. The proportion of men scoring greater than 7 approximately doubled with each decade of age. Our estimation indicated that in 1992 approximately 1.14 million French men had moderate to severe urinary symptoms that were likely to be associated with benign prostatic hyperplasia. Previous studies had yielded higher prevalence estimates, probably due to differences in sampling design and diagnostic criteria.

Using Cox's Proportional Hazard Model, we have demonstrated the influence of age, sex, microscopic tumour type, extent of primary tumour, nodal status and the presence of metastases on prognosis, in our population of 441 patients with thyroid carcinoma. The TNM classification contributes significantly to survival, but does not include other contributory prognostic variables, whereas the prognostic index developed by the EORTC thyroid study group, which takes account of age and histology, proved a reliable predictor of survival for our patient group.

Nitrate dissimilation in chemostat grown cultures ofClostridium butyricum SS6 has been investigated. Sucrose limited cultures grown on nitrate produced nitrite as the principal end-product of nitrate reduction whilst under nitrate-limiting conditions ammonia accumulated in the spent media. Nitrate reduction was accompanied by the synthesis of a soluble nitrate reductase (123 nmol·NADH oxidised · min-1 · mg protein-1) and in addition, under N-limiting conditions, a soluble nitrite reductase (56 nmol NADH oxidised min-1 · mg protein-1). Corresponding ammonia grown cultures synthesised neither enzyme. Concurrent with the dissimilation of nitrate to nitrite and ammonia cell population densities increased by 18% (C-limitation) and 32% (N-limitation). Spent media analyses of the fermentation products from ammonia and nitrate grown cells showed the accumulation of acetate in nitrate dissimilating cultures. Molar ratios of acetate/butyrate increased by a factor of 5 (C-limitation) to 12 (N-limitation) upon adding nitrate to the growth medium. In C-limited cultures, grown on nitrate, hydrogenase activity was 340 nmol · min-1 · mg protein-1 and under N-limitation this increased to 906 nmol · min-1 · mg protein-1. Since N-limited cultures are electron acceptor limited, the increase in hydrogenase activity enables excess electrons to be spilled by this route.

Certain strains of Streptococcus sanguis adhere (Adh+) selectively to human platelets and, in plasma, induce them to aggregate (Agg+) into in vitro thrombi. In this study, we examined 18 recent endocarditis and dental plaque isolates of microorganisms that were biotyped as S. sanguis for coexpression of platelet interactivity phenotypes with another possible virulence factor in bacterial endocarditis, dextran synthesis. Detectable production of extracellular glucosyltransferase ranged from 0.2 to 66 mU/mg of culture fluid for 10 representative strains tested. Production of extracellular or cell-associated glucosyltransferase, fructosyltransferase, and soluble or insoluble dextrans was not necessarily coexpressed with platelet interactivity phenotypes, since the levels of production of soluble and insoluble dextrans varied among representative Adh+ Agg+ and Adh- Agg- strains. Analysis of a second panel of 38 fresh dental plaque isolates showed that S. sanguis distributes in a reproducible manner into the possible phenotype groups. Strains with different platelet interactivity phenotypes were distinguished with a panel of four murine monoclonal antibodies (MAbs) raised against Adh+ Agg+ strain 133-79 and screened to rule out artifactual reactions with antigenic components in culture media. The MAbs reacted selectively with Adh+ Agg+ strains in a direct-binding, whole-cell, enzyme-linked immunosorbent assay and also inhibited their interactions with platelets. Analysis of minimal tryptic digests of many strains, including variants that failed to bind the MAbs, suggested that some noninteractivity phenotypes possess cryptic surface determinants. Since the ability to adhere to platelets and induce them to aggregate is relatively stable, these traits may be useful in a phenotyping scheme for these Lancefield nontypeable streptococci.

A strain of Streptococcus sanguis that induced rabbit platelets to aggregate in vitro (Agg+ phenotype) was hypothesized to be a more virulent pathogen than an Agg- strain in experimental endocarditis in rabbits. A left ventricular catheter was implanted, and then an Agg+ or Agg- strain was inoculated intravenously. Vegetations formed on the aortic semilunar valves but were unaffected by the duration of implantation of the catheter. Vegetations enlarged by accumulating platelets and their mass increased directly with the duration of endocarditis. Inoculation of the Agg+ strain consistently caused endocarditis with significantly larger vegetations, a more severe clinical course (including febrile episodes, hematological changes, and signs of myocardial ischemia), more gross lesions in major organs, and greater mortality than inoculation with the Agg- strain, saline, or the Agg+ strain pretreated with monospecific rabbit immunoglobulin G or Fab fragments against its platelet aggregation-associated protein (PAAP; class II). In experimental endocarditis, PAAP expressed by Agg+ S. sanguis appeared to be an important virulence factor.

Rhodopseudomonas acidophila strain 7050 achieved balanced growth when provided with either asparagine or glutamine as nitrogen source. Under these growth conditions R. acidophila synthesized a mixed amidase which exhibited similar activity (223–422 nmol/min·mg protein) against either nitrogen source. Determination of the free intracellular amino acid pools show that deamidation of asparagine and glutamine resulted in elevated levels of both aspartate and glutamate. Cell-free extracts of R. acidophila showed significant aminotransferase activity, particulary glutamine-oxaloacetate aminotransferase (89.7–209.3 nmol/min·mg protein), glycine oxaloacetate aminotransferase (135–227 nmol/min ·mg protein), alanine glyoxylate aminotransferase (66.3–163.2 nmol/min·mg protein) and serineglyoxylate aminotransferase (57.1–68.4 nmol/min ·mg protein). Short term labelling experiments using 14C-glyoxylate show that glycine plays an important role in amino nitrogen transfer in R. acidophila and that the enzymes for the metabolism of glyoxylate via glycine, serine and hydroxypyruvate were present in cell-free extracts. These data confirm that R. acidophila can satisfy all its' nitrogen requirements by transamination.

Glucose was required for the transport of arabinose into Bifidobacterium breve. The non-metabolisable glucose analogue 2-deoxy-d-glucose (2-DG) did not facilitate assimilation of arabinose. Studies using d-[U-14C]-labelled arabinose showed that it was fermented to pyruvate, formate, lactate and acetate, whereas the principal metabolic products of d-[U-14C]-labelled glucose were acetate and formate. In contrast to glucose, arabinose was not incorporated into cellular macromolecules. A variety of metabolic inhibitors and inhibitors of sugar transport (proton ionophores, metal ionophores, compounds associated with electron transport) were used to investigate the mechanisms of sugar uptake. Only NaF, an inhibitor of substrate level phosphorylation, and 2-DG inhibited glucose assimilation. 2-DG had no effect on arabinose uptake, but NaF was stimulatory. High levels of phosphorylation of glucose and 2-DG by PEP and to a lesser degree, ATP were seen in phosphoenolpyruvate: phosphotransferase (PEP:PTS) assays. These data together with strong inhibition of glucose uptake by NaF suggest a role for phosphorylation in the transport process. Arabinose uptake in B. breve was not directly dependent on phosphorylation or any other energy-linked form of transport but may be assimilated by glucose-dependent facilitated diffusion.

High levels of amines were present in large intestinal material taken from five persons who had died suddenly. Mean total concentrations of simple aliphatic amines were approximately 22 mmol/kg in the proximal colon and 16 mmol/kg in the distal bowel, with propylamine, piperidine and methylamine predominating in all regions. Amine concentrations in faeces from six healthy donors ranged from 1·8 to 41·5 mmol/kg (mean 13·3, S.E.M. 5·9). A wide range of these metabolites was found in intestinal contents, of which trimethylamine and propylamine were quantitatively most important. Although considerable inter-individual variation was seen in faecal amine excretion, methylamine and dimethylamine were never detected in fresh faeces, indicating these substances were rapidly absorbed from the rectum. Net production rates of different amines in faecal material incubatedin vitrovaried from approximately 0·01 μmol/h/g for methylamine, cadaverine, histamine and tryptamine, to 1·26 μmol/h/g in the case of propylamine. Amines were further metabolised by colonic bacteria, especially in the presence of a fermentable carbohydrate source. Amine formation by faecal bacteria was maximal at near neutral pH, while culture in the presence of a fermentable carbohydrate source reduced net amine production by 80%.Confirmatory evidence for the importance of pH and carbohydrate availability on amine production was obtained in experiments with 16 pure cultures of intestinal bacteria. Most probable number (MPN) counts of amine producing bacteria in faeces from four healthy donors showed that high numbers of methylamine, dimethylamine and propylamine forming bacteria were present in every sample. However, considerable variability was seen in carriage rates of bacteria forming other amines, especially with respect to histamine, butylamine and phenylethylamine. Measurements of individual amine concentrations in MPN tubes showed that propylamine constituted about 70% of total amine production at all sample dilutions, and that while high populations of histamine forming bacteria were present in faecal samples, very small amounts of this product were formed.

We examined the direct effects of nicotine on a variety of neutrophil functions at concentrations achievable in lung and oral tissues from cigarette smoking. The results show dose-dependent suppression of chemotaxis and phagocytosis, and enhancement of degranulation and eicosanoid generation, but not superoxide production. Cell viability was not affected by the concentrations of nicotine used in these experiments, as shown by trypan blue dye exclusion and MTT assays. These results implicate nicotine as the ingredient in cigarette smoke responsible for inflammatory damage to lungs and oral tissues observed in cigarette smokers.

OBJECTIVES: To investigate the claim that 90% of episodes of low back pain that present to general practice have resolved within one month. DESIGN: Prospective study of all adults consulting in general practice because of low back pain over 12 months with follow up at 1 week, 3 months, and 12 months after consultation. SETTING: Two general practices in south Manchester. 490 subjects (203 men, 287 women) aged 18-75 years. MAIN OUTCOME MEASURES: Proportion of patients who have ceased to consult with low back pain after 3 months; proportion of patients who are free of pain and back related disability at 3 and 12 months. RESULTS: Annual cumulative consultation rate among adults in the practices was 6.4%. Of the 463 patients who consulted with a new episode of low back pain, 275 (59%) had only a single consultation, and 150 (32%) had repeat consultations confined to the 3 months after initial consultation. However, of those interviewed at 3 and 12 months follow up, only 39/188 (21%) and 42/170 (25%) respectively had completely recovered in terms of pain and disability. CONCLUSIONS: The results are consistent with the interpretation that 90% of patients with low back pain in primary care will have stopped consulting with symptoms within three months. However most will still be experiencing low back pain and related disability one year after consultation.

We demonstrate a novel technique for converting a continuous-wave laser beam into a stable train of short pulses with a high repetition rate. The system, which is generally applicable, is based on a purely passive coupled-cavity optical frequency comb generator, which ensures a high overall efficiency. The repetition rate of the device is determined by the drive frequency of an electro-optic modulator and the pulse width by the rf power applied to the modulator. We have observed pulses down to 3.3 ps long at a 5.34-GHz repetition rate and an overall efficiency of 11%. The experimental results for pulse shape and width show excellent quantitative agreement with the results of a simple model.