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S Macfarlane

Publications and source records attributed to S Macfarlane.

At least 19 recordsLinked to original sources
PubMed2006

Review article: prebiotics in the gastrointestinal tract.

BACKGROUND: Prebiotics are short-chain carbohydrates that alter the composition, or metabolism, of the gut microbiota in a beneficial manner. It is therefore expected that prebiotics will improve health in a way similar to probiotics, whilst at the same time being cheaper, and carrying less risk and being easier to incorporate into the diet than probiotics. AIM: To review published evidence for prebiotic effects on gut function and human health. METHODS: We searched the Science Citation Index with the terms prebiotic, microbiota, gut bacteria, large intestine, mucosa, bowel habit, constipation, diarrhoea, inflammatory bowel disease, Crohn's disease, ulcerative colitis, pouchitis, calcium and cancer, focussing principally on studies in humans and reports in the English language. Search of the Cochrane Library did not identify any clinical study or meta-analysis on this topic. RESULTS: Three prebiotics, oligofructose, galacto-oligosaccharides and lactulose, clearly alter the balance of the large bowel microbiota by increasing bifidobacteria and Lactobacillus numbers. These carbohydrates are fermented and give rise to short-chain fatty acid and intestinal gas; however, effects on bowel habit are relatively small. Randomized-controlled trials of their effect in a clinical context are few, although animal studies show anti-inflammatory effects in inflammatory bowel disease, while calcium absorption is increased. CONCLUSIONS: It is still early days for prebiotics, but they offer the potential to modify the gut microbial balance in such a way as to bring direct health benefits cheaply and safely.

Bone and Bones↗
PubMed2006

The semi-permeability of silicone: a saline-filled breast implant with intraluminal and pericapsular Aspergillus flavus.

Fungal infection of breast implants is a rare complication. Growth of fungi within the lumen of saline-filled implants has previously been demonstrated in laboratory studies, however, clinical infections are rare. We report a case of Aspergillus flavus growth within and around a saline-filled breast implant that was inserted 18 months previously. This was successfully treated with implant removal and wound irrigation. Possible routes of microbial contamination as well as survival mechanisms of organisms within saline-filled implants are discussed. This case re-iterates that the silicone envelope of a saline-filled implant is selectively permeable and we believe this is instrumental in facilitating intraluminal microbial growth. This also emphasises the importance of stringent asepsis when dealing with saline-filled breast implants including avoiding contamination of the saline filling fluid.

Adult↗
PubMed2005

Imaginem oblivionis: the prospects of neuroimaging for early detection of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by the gradual onset of dementia. The pathological hallmarks of the disease are A beta amyloid plaques, neurofibrillary tangles, and reactive gliosis. Current diagnosis of AD is made by clinical, neuropsychologic, and neuroimaging assessments. Routine structural neuroimaging evaluation is based on non-specific features such as atrophy, a late feature in the progression of the disease, hence the crucial importance of developing new approaches for early and specific recognition at the prodromal stages of AD. Functional neuroimaging techniques such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) could prove to be valuable in the differential diagnosis of AD, as well as in assessing prognosis. With the advent of new therapeutic strategies aimed at reducing the A beta amyloid burden in the brain, there is increasing interest in the development of PET and SPECT radioligands that will permit the assessment of A beta amyloid burden in vivo. From this, the prospect of specific preclinical diagnosis arises, possibly in conjunction with other related A beta biomarkers in plasma and CSF.

Alzheimer Disease↗
PubMed2005

Mucosal bacteria in ulcerative colitis.

Ulcerative colitis (UC) is an acute and chronic inflammatory bowel disease of unknown aetiology, although bacterial species belonging to the normal colonic microbiota are known to be involved in its initiation and maintenance. Several organisms have been linked to the disease; however, mucosa-associated bacteria are more likely to be involved than their luminal counterparts, due to their close proximity to the host epithelium. Comparative bacteriological analyses were done on rectal biopsies to investigate differences in mucosal bacteria in patients with UC and healthy controls. Complex bacterial communities were found in both groups, with significant reductions in bifidobacterial numbers in UC, which suggested that they might have a protective role in the disease. Accordingly, a therapy for treating UC was designed, with the aim of modifying the mucosal microbiota to increase bifidobacterial colonisation and reduce inflammation. Ranges of mucosal and faecal bifidobacteria were tested for their substrate preferences and their abilities to survive under a variety of environmental conditions. A synbiotic comprising a probiotic (Bifidobacterium longum) isolated from healthy rectal mucosa combined with a prebiotic (oligofructose-enriched inulin - Synergy 1) was developed. The treatment was used in a randomised controlled trial involving eighteen patients with active UC, for a period of 1 month. Rectal biopsies were collected at the beginning and end of the study. Bacteriological analysis and transcription levels of epithelium-related immune markers were assessed. Results demonstrated that short-term synbiotic treatment resulted in increased bifidobacterial colonisation of the rectal mucosa and induced significant reductions in the expression of molecules that control inflammation in active UC.

Adult↗
PubMed2005

Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial.

BACKGROUND AND AIMS: Ulcerative colitis (UC) is an acute and chronic inflammatory disease of the large bowel with unknown aetiology. The immune response against normal commensal microorganisms is believed to drive inflammatory processes associated with UC. Therefore, modulation of bacterial communities on the gut mucosa, through the use of probiotics and prebiotics, may be used to modify the disease state. METHODS: A synbiotic was developed for use in UC patients combining a probiotic, Bifidobacterium longum, isolated from healthy rectal epithelium, and a prebiotic (Synergy 1), a preferential inulin-oligofructose growth substrate for the probiotic strain. Treatment was employed in a double blinded randomised controlled trial using 18 patients with active UC for a period of one month. Clinical status was scored and rectal biopsies were collected before and after treatment, and transcription levels of epithelium related immune markers were measured. RESULTS: Sigmoidoscopy scores (scale 0-6) were reduced in the test group (start 4.5 (1.4), end 3.1 (2.5)) compared with placebo (start 2.6 (2.1), end 3.2 (2.2)) (p=0.06). mRNA levels for human beta defensins 2, 3, and 4, which are strongly upregulated in active UC, were significantly reduced in the test group after treatment (p=0.016, 0.038, and 0.008, respectively). Tumour necrosis factor alpha and interleukin 1alpha, which are inflammatory cytokines that drive inflammation and induce defensin expression, were also significantly reduced after treatment (p=0.018 and 0.023, respectively). Biopsies in the test group had reduced inflammation and regeneration of epithelial tissue. CONCLUSIONS: Short term synbiotic treatment of active UC resulted in improvement of the full clinical appearance of chronic inflammation in patients receiving this therapy.

Adult↗
PubMed2004

Bacterial milieu and mucosal bacteria in ulcerative colitis.

The aetiology of ulcerative colitis (UC) is unknown, but there is evidence that bacteria are needed for initiation and maintenance of the disease. A number of organisms have been associated with UC, but evidence for a specific transmissible agent is weak. Despite this, there is a good case for mucosal bacterial involvement, either through pathogens colonizing the epithelial surface, by non-pathogenic commensal species occupying adhesion sites on the mucosa and preventing invasion by harmful bacteria, or by inappropriate host immune responses to members of the normal microflora. Since mucosal bacteria exist in close juxtaposition to host tissues, it might be expected that they interact to a greater extent with the immune and neuroendocrine systems than their luminal counterparts. For this reason, comparative bacteriological analyses were done on rectal biopsies from patients with active colitis, and individuals who had no inflammatory bowel disease. Complex bacterial communities colonized the rectal mucosa in all subjects and great interindividual variabilities in mucosal bacterial populations were observed in both groups. These organisms often occurred in microcolonies, which may have implications for UC, since it would result in higher localized concentrations of bacterial antigens, or toxins, than would be the case if the organisms were diffusely spread across the mucosa.

Bacterial Adhesion↗
PubMed2004

Identification and quantitation of mucosal and faecal desulfovibrios using real time polymerase chain reaction.

BACKGROUND: Desulfovibrios produce sulphide, which is toxic to colonic epithelial cells. These bacteria have previously been linked to ulcerative colitis. Traditional methods of culturing these organisms are slow, and often unreliable, while molecular approaches are either non-quantitative or lack sensitivity. AIMS: To develop a sensitive method for quantitating desulfovibrios in stools and biopsy tissue, and to investigate the effects of age and disease on these bacteria. METHODS: Rectal biopsies were taken from 10 colitis patients and 10 healthy controls. Stool samples were obtained from 10 healthy infants (mean age 1.01 (0.18) years), 10 healthy young adults (26.7 (1.2) years), and 10 healthy elderly people (71.7 (1.2) years). Primers were designed and developed for analysing Desulfovibrio populations in the bowel using real time polymerase chain reaction (PCR). RESULTS: The PCR primers were highly specific for desulfovibrios. Large numbers (approximately 10(6)-10(7)/g) occurred in biopsies in colitis patients and healthy subjects, and no disease related differences were observed. Measurements of mucosal desulfovibrios over 12 months showed marked changes in some patients. Infants (10(6)-10(7)/g) and elderly people (10(7)-10(8)/g) had significantly higher numbers of desulfovibrios in stools compared with young adults (10(5)/g). CONCLUSIONS: Real time PCR analysis of desulfovibrios was an efficient and accurate method for studying these potentially harmful microorganisms. Desulfovibrios were ubiquitous in the bowel, irrespective of age. As rectal mucosae were heavily colonised in health and disease, if these bacteria play a role in colitis, some host defect, possibly in sulphide detoxication pathways or in bacterial antigen handling, is required for manifestations of pathogenicity.

Adult↗
PubMed2004

Systemic antibodies towards mucosal bacteria in ulcerative colitis and Crohn's disease differentially activate the innate immune response.

BACKGROUND AND AIMS: The mucosa in ulcerative colitis (UC) is replete with antibody producing plasma B cells and polymorphonuclear leucocytes (PMN). This combination of effector cells requires a crosslinking antigen to evoke an antibody driven PMN inflammatory response via their Fc receptors. The stimulus for activation is thought to be commensal bacteria colonising the gut mucosa. The aim of this investigation was to compare the principal culturable bacterial populations on the rectal mucosa of UC patients, and to determine whether specific antibodies towards these bacteria can activate infiltrating PMN through opsonisation. This would provide an explanation for this chronic inflammatory condition. METHODS: Bacteria colonising rectal tissue were characterised using chemotaxonomic techniques. Systemic antibody responses were measured against total antigens and surface antigens of these organisms in UC and Crohn's disease (CD) patients, together with healthy controls. Antibody enhancement of the respiratory burst in PMN was also investigated, against a range of mucosal isolates. RESULTS: Distinct differences were observed in some bacterial populations in UC biopsies, which were generally reflected in antibody responses towards these organisms. UC patients had higher IgG responses to surface antigens, primarily IgG1, whereas the response in CD was mainly IgG2. Antibodies from UC patients greatly enhanced the respiratory burst in PMN, in response to individual bacterial species. CONCLUSIONS: Changes in mucosal bacteria, and a switch from internal to surface antigen/antibody reactivity of a predominantly IgG1 type, leads to greater opsonisation of the respiratory burst in PMN, providing a mechanism for maintaining the inflammatory state in UC.

Aged↗
PubMed2003

The impact upon extra-pyramidal side effects, clinical symptoms and quality of life of a switch from conventional to atypical antipsychotics (risperidone or olanzapine) in elderly patients with schizophrenia.

BACKGROUND: Atypical antipsychotics are commonly used in the management of schizophrenia in late life with evidence suggesting they induce lower rates of motor disturbance, but have similar efficacy to conventional antipsychotics. Trials in the elderly have been either retrospective, small, of short duration or of a single-arm design. AIMS: To demonstrate the effects upon motor side-effects, efficacy, safety and quality of life (QOL) of switching elderly patients with schizophrenia from conventional antipsychotics to olanzapine or risperidone. METHODS: Elderly patients with schizophrenia were randomly allocated to olanzapine or risperidone and followed through an open-label crossover period. Between and within group intention to treat analyses were conducted. RESULTS: 66 patients were randomised (mean age 69.6 [SD +/- 6.2]). Four (11.8%) patients on olanzapine and 8 (26.7%) patients on risperidone failed to complete the crossover because of treatment failure [Odds Ratio (OR) = 2.73[0.73-10.2] p = 0.14]. The mean doses upon completion of switching in each arm were 9.9 mg (SD = 4.2) and 1.7 mg (SD = 1.2) for olanzapine and risperidone respectively. In both arms there was improvement in Parkinsonism, though only olanzapine was associated with a reduction in dyskinetic symptoms. The Brief Psychiatric Rating Scale, Scale for the assessment of Negative Symptoms and Montgomery and Asberg Depression Rating Scale scores all improved through the crossover period in both arms with no between group differences. Treatment with olanzapine was associated with a better response over risperidone on the psychological domain of the World Health Organisation-Quality Of Life [Brief] (WHO-QOL-BREF) scale ( p = 0.02). Patients in the olanzapine arm also demonstrated improvement from baseline in the WHO-QOL-BREF physical, psychological and health satisfaction domains, but risperidone had no effect on any Quality of Life (QOL) measure. CONCLUSIONS: After switching from a conventional antipsychotic, olanzapine and risperidone were associated with improvement in core symptoms of schizophrenia and motor side effects. Subjects switched to olanzapine were more likely to complete the switching process and show an improvement in psychological QOL.

Aged↗
PubMed2003

Intestinal bacteria and ulcerative colitis.

Convincing evidence from both animal models and the study of patients with ulcerative colitis (UC) implicates the intestinal microflora in the initiation and maintenance of the inflammatory processes in this condition. Despite this, no specific pathogen has been identified as causal and the disease is widely believed to occur as the result of a genetically determined, but abnormal immune response to commensal bacteria. When compared with healthy people, UC patients have increased levels of mucosal IgG directed against the normal microflora. Studies of mucosal bacterial populations in UC indicate that there may be increased numbers of organisms, but reduced counts of "protective" bacteria such as lactobacilli and bifidobacteria. In animal models of colitis, antibiotics, particularly metronidazole, clindamycin, ciprofloxacin and the combination of vancomycin/impinemem protect against UC, especially if given before the onset of inflammation. These antibiotics target anaerobes and some Gram-positive organisms such as enterococci. However, antibiotic use in more than a dozen randomised control trials has been very disappointing, probably because we do not know which species to target, when to give the antibiotics, for how long and in what combinations. Surprisingly, therefore, there is a consistent benefit in the small number of studies reported of probiotics to manage UC and pouchitis. There is scope for more work in this area focussing on the mucosal microflora, its interactions with the gut immune system, its metabolic properties and the potential ways of modifying it.

Animals↗
PubMed2001

Toxin synthesis and mucin breakdown are related to swarming phenomenon in Clostridium septicum.

Clostridium septicum is responsible for several diseases in humans and animals. The bacterium is capable of a simple kind of multicellular behavior known as swarming. In this investigation, environmental and physiologic factors affecting growth and swarm cell formation in C. septicum were studied over a range of dilution rates (D = 0.02 to 0.65 h(-1)) in glucose-limited, glucose-excess, and mucin-limited chemostats. Cellular differentiation was observed at low specific growth rates, irrespective of the carbon and energy source, showing that swarming occurred in response to nutrient depletion. Differential expression of virulence determinants was detected in swarm cells. Hemolysin was secreted by short motile rods but not swarm cells, whereas in cultures grown with glucose, only swarm cells formed DNase, hyaluronidase, and neuraminidase. However, neuraminidase and, to a lesser degree, hyaluronidase were induced in short motile rods in mucin-limited cultures. Both swarm cells and short rods were cytotoxic to Vero cells. Mucin was chemotaxic to C. septicum, and large amounts of mucin-degrading enzymes (beta-galactosidase, N-acetyl beta-glucosaminidase, glycosulfatase, and neuraminidase) were produced. Synthesis of these enzymes was catabolite regulated. In chemostat experiments, glycosulfatase secretion occurred only in swarm cells at low dilution rates in mucin-limited cultures. Determinations of oligosaccharide utilization demonstrated that N-acetylglucosamine, galactose, and N-acetylgalactosamine were the main carbon sources for C. septicum in mucin. Neuraminic acid was not assimilated, showing that neuraminidase does not have a direct nutritional function in this pathogen.

Bacterial Toxins↗
PubMed2000

Public health in developing countries.

Poverty not only excludes people from the benefits of health-care systems but also restricts them from participating in decisions that affect their health. The resulting health inequalities are well documented, and the search for greater equity attracts many concerned players and initiatives. Fundamental to the success of these efforts, however, is the need for people to be able to negotiate their own inclusion into health systems and demand adequate health care. This calls for a restatement of the centrality of people in public health and its practice. New forms of communication and cooperation are required at all levels of society, nationally, and internationally, to ensure equitable exchange of views and knowledge to formulate appropriate action to redress inequalities and improve people's health and wellbeing.

Developing Countries↗
PubMed1999

High incidence of treatment failure with vincristine, etoposide, epirubicin, and prednisolone chemotherapy with successful salvage in childhood Hodgkin disease.

BACKGROUND AND PROCEDURE: In an attempt to further reduce the long-term toxicity of chemotherapy for childhood Hodgkin disease (HD), the Australian and New Zealand Children's Cancer Study Group between 1990 and 1996 enrolled 53 children with biopsy-proven and imaging-staged HD into a chemotherapy-only treatment regimen using 5-6 courses of vincristine, etoposide, epirubicin, and prednisolone (VEEP). RESULTS: There were 23 events in these children with 3 progressive disease (PD), 8 partial remissions (PR), and 12 relapses. In the stage I patients, there were 8 events (35%). There was no association between the number of events and the stage of HD. Massive mediastinal disease at diagnosis was present in 16 patients, 11 of whom had an event with 3 PD, 3 PR, and 5 relapses. For all patients with an event at 6-24-month follow-up, all but two patients were salvaged with either alkylating agent-based chemotherapy alone or with irradiation and chemotherapy. The event-free survival for the whole group with median follow-up of 33 months was 59%, but only 31% for massive mediastinal disease. Disease-free survival was 78% and overall survival at 60 months was 92%, with one death due to drug-induced aplasia and another from acute myeloid leukemia. CONCLUSIONS: We conclude that VEEP chemotherapy in childhood HD used as the only treatment modality has an unacceptably high treatment failure rate in patients with massive mediastinal disease and 35% incidence of treatment failure in stage I disease.

Adolescent↗
PubMed1998

Growth of a human intestinal Desulfovibrio desulfuricans in continuous cultures containing defined populations of saccharolytic and amino acid fermenting bacteria.

Ecological and physiological effects of the sulphate-reducing bacterium (SRB) Desulfovibrio desulfuricans on other intestinal organisms were investigated in anaerobic chemostats (dilution rate approximately 0.2 h-1). Reproducible defined bacterial communities were used in these experiments, comprising 14 different saccharolytic and amino acid fermenting species: Bifidobacterium longum, Bif. adolescentis, Bif. pseudolongum, Bif. infantis, Bacteroides thetaiotaomicron, Bact. vulgatus, Lactobacillus acidophilus, Enterococcus faecalis, Ent. faecium, Escherichia coli, Clostridium perfringens, Cl. butyricum, Cl. innocuum, Cl. bifermentans. Lactobacillus and Cl. bifermentans populations never rose above minimum detection limits (log10 2.0 and 4.0, respectively) under the experimental conditions employed in these studies. Inclusion of Des. desulfuricans in bacterial cultures (c. log10 8.4 viable cells ml-1) resulted in marked reductions (i.e. greater than 1 log) in planktonic cell population densities of several species, particularly Bif. longum, Cl. perfringens and Bif. pseudolongum. The two bacteroides species were unaffected by Des. desulfuricans, while numbers of Cl. butyricum increased. Extensive wall growth developed in the SRB culture, consisting mainly of Des. desulfuricans (log10 9.2 viable cells ml-1), Bact. thetaiotaomicron and Bact. vulgatus, with lesser numbers of facultative anaerobes, Cl. perfringens and Bif. longum. Wall growth was associated with a reduction in planktonic cell mass and increased acid production by the cultures. Chemotaxonomic study of chemostat microbiotas, on the basis of cellular fatty acid methyl ester (FAME) analyses, showed the existence of characteristic bacteroides (C15) and bifidobacterial (C18) markers, but desulfovibrio markers (i-C15:0, C16:0, i-C17:1) could be identified. The metabolic activities of saccharolytic organisms were altered in the SRB chemostat, including synthesis of a number of hydrolytic enzymes involved in carbohydrate breakdown, such as alpha-galactosidase, alpha-glucosidase and beta-galactosidase, together with several mucinolytic enzymes. High concentrations of sulphide (8.2 mmol 1-1) were detected in the SRB chemostat, suggesting that this metabolite may have been inhibitory to some species. Saccharolytic organisms growing in the SRB fermenter utilized more starch, but less galactose-containing polymers, which correlated with the observed glycosidase activities. Profound differences were also recorded with respect to fermentation product formation in the chemostats, where a major switch to acetate production occurred in the SRB culture, with concomitant reductions in propionate, butyrate and lactate, which is an important electron donor for desulfovibrios.

Amino Acids↗
PubMed1998

A case of verbal auditory agnosia: missing the word ... missing the sound....

The neuropsychological nature of verbal auditory agnosia is not fully understood. This study aims to describe the language deficits and the remediation strategies used in a person with verbal auditory agnosia. In addition, it will address the theoretical issues concerning the nature of the phenomenon and the clinical implications in the management of people with this disorder.

Aged↗