M J Farthing

St George's, University of London, Londinium, England, United Kingdom

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Publications (134)1309.4 Total impact

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    ABSTRACT: Adults with acquired immune deficiency syndrome and persistent diarrhoea in Zambia have intestinal infection, predominantly protozoa. To search for treatment which can be offered with minimal investigation, we carried out a double-blind, randomized-controlled trial of nitazoxanide (a drug with a range of activity against parasites and bacteria). Patients with diarrhoea of 1 month duration or longer were randomized to receive nitazoxanide (1000 mg twice daily) or placebo for 2 weeks. End-points were clinical response, parasitological clearance and mortality. Two hundred and seven adults were randomized; 42 died during the study. The primary assessment of efficacy was made after 17 days. Clinical response was observed in 56 (75%) of 75 patients receiving nitazoxanide and 45 (58%) of 77 patients receiving placebo (P = 0.03). The rate of improvement was markedly higher in patients with CD4 counts under 50 cells/microL receiving nitazoxanide (P = 0.007). The benefit was largely restricted to the period when the drug was being administered. No difference was seen in parasitological clearance between the two groups. Mortality was 19% by 4 weeks of follow-up and did not differ with treatment allocation. Nitazoxanide given orally for 14 days was associated with clinical improvement in Zambian acquired immune deficiency syndrome patients with diarrhoea, especially those with very low CD4 counts.
    Alimentary Pharmacology & Therapeutics 04/2005; 21(6):757-63. DOI:10.1111/j.1365-2036.2005.02394.x · 5.48 Impact Factor
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    ABSTRACT: To determine the response of the small intestinal mucosa to environmental conditions, we studied changes in mucosal architecture and function in a longitudinal cohort study in African adults. Over three consecutive years, 238 adults submitted monthly stool samples for parasitologic and bacteriologic analysis and underwent an annual endoscopic jejunal biopsy for mucosal morphometry. Absorption and permeability assays were performed on the same day as the enteroscopy. Variation in mucosal architecture and function was correlated with environmental factors and stool microbiology. The whole cohort had structural and functional evidence of tropical enteropathy, but structure and function were only weakly correlated. There were marked changes over time, and seasonal variation was observed in villous height (16%), xylose recovery (16%), and permeability (28%). Asymptomatic intestinal infections were common. Enteropathy was more severe in participants with Citrobacter rodentium or hookworm ova in the stool sample taken one month before the investigations were performed.
    The American journal of tropical medicine and hygiene 05/2004; 70(4):412-9. · 2.74 Impact Factor
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    ABSTRACT: Identification of patients likely to experience high levels of discomfort during unsedated gastroscopy would be useful as these patients could be prospectively targeted for sedation. We prospectively assessed patient and endoscopic variables in subjects attending for endoscopy in order to identify factors associated with patients' experience of the unsedated examination. We studied 508 patients attending for routine diagnostic gastroscopy. Clinical and endoscopic data were collected and patients completed a two-part questionnaire assessing their anxiety with, and experience of, the procedure. Thirty-nine subjects failed to complete the initial unsedated endoscopy. Failure to tolerate endoscopy was associated with younger age (P = 0.002) and examination with a standard-bore (> or = 9.0 mm) endoscope (P = 0.004). High levels of patient discomfort during the procedure were associated with younger age (P < 0.001), high levels of pre-endoscopic anxiety (P < 0.001), high levels of pre-endoscopic discomfort due to throat spray (P = 0.02) and examination with a standard-bore endoscope (P < 0.001). Preference for sedation during future examinations was related to female gender (P = 0.02), young age (P = 0.02), high levels of apprehension (P < 0.001), the examining doctor (P = 0.002) and use of a standard-bore endoscope (P < 0.001). Discrete clinical characteristics and endoscopic variables are associated with patients' experience of unsedated endoscopy. Further work might result in an algorithm for identifying patients who would benefit from sedation prior to gastroscopy.
    Scandinavian Journal of Gastroenterology 01/2002; 36(12):1352-7. · 2.33 Impact Factor
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    ABSTRACT: Delayed puberty is a frequent complication of inflammatory bowel disease. The precise etiological mechanisms are not known. In this study, we wanted to determine the relative contribution of undernutrition and inflammation to delayed puberty and the effect of inflammation on the reproductive axis. Puberty was assessed in rats with 2,4,6-trinitrobenzenesulfonic acid induced-colitis, healthy controls, and animals pair fed to match the food intake of the colitic group. The response to testosterone administration was assessed in colitic rats. We found that induction of colitis was associated with hypophagia and reduced weight gain, and undernutrition in healthy females (i.e., pair fed) resulted in a delay in the onset (by 4.8 days, P < 0.001) and progression of puberty (normal estrous cycles in 42%, P = 0.04) compared with controls. However, puberty was further delayed in the colitic group (1.4 days after pair fed) with the absence of normal estrous cycling in all rats. In males, the onset of puberty was also delayed, and weights of accessory sex organs were reduced compared with pair-fed controls. Plasma testosterone concentrations were low, and gonadotropin concentrations were normal in colitic rats. Testosterone treatment normalized puberty in male rats with colitis. In conclusion, in rats with experimental colitis, inflammation appears to potentiate the effect of undernutrition on puberty. The weights of secondary sex organs and the onset of puberty were normalized by testosterone treatment.
    AJP Regulatory Integrative and Comparative Physiology 11/2001; 281(5):R1483-91. · 3.53 Impact Factor
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    ABSTRACT: The role of mucosal T-cell activation in HIV-associated enteropathy is uncertain. Twenty Zambian patients with AIDS and chronic diarrhea were studied, as were nine controls. Distal duodenal biopsies were taken at endoscopy. Morphometric analysis and dual color immunofluorescence staining were performed. Villous height was reduced [177 (118-228) vs 305 (244-358) microm P = 0.002] and crypt depth increased [220 (164-202) vs 194 (164-202) microm P = 0.008] in AIDS patients compared to controls. CD3+CD4+ T cells were reduced in AIDS patients compared to controls [12.9 (5.7-25.2) vs 47.6 (33.4-65.5)% P = 0.04]. There was no significant difference in expression of CD8, CD25, CD69, HML-1, or HLA-DR on T cells between the AIDS patients and controls, with the exception of CD3+HML-1+ cells, which were increased in AIDS patients (P = 0.05). Small intestinal T-cell activation was similar between AIDS patients and controls. We conclude, therefore, that this mechanism is not likely to be important in the pathogenesis of HIV-associated enteropathy.
    Digestive Diseases and Sciences 06/2001; 46(5):1133-8. DOI:10.1023/A:1010738818127 · 2.55 Impact Factor
  • Gastroenterology 04/2001; 120(5). DOI:10.1016/S0016-5085(01)82198-3 · 12.82 Impact Factor
  • Gastroenterology 04/2001; 120(5). DOI:10.1016/S0016-5085(08)81045-1 · 12.82 Impact Factor
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    ABSTRACT: Upper gastrointestinal endoscopy is performed without sedation in many countries. Unsedated patients experience more discomfort during endoscopy than sedated patients, but few studies have examined factors which could be modified to minimize discomfort during the procedure. We assessed the effect of endoscope diameter on patient discomfort during unsedated transoral gastroscopy. A total of 322 patients attending for unsedated endoscopy were examined using an endoscope of diameter either 6.0 mm or 9.8 mm. Patients completed a two-part questionnaire assessing tolerance of the procedure and discomfort during it. There was failure to complete the initial unsedated endoscopy in three of 163 patients in the 6.0 mm group and 14 of 159 in the 9.8 mm group (P = 0.009). Patients in the 6.0 mm group reported less discomfort both during endoscope insertion (P < 0.0001) and during the remainder of the procedure (P < 0.0001). 14% of patients in the 6.0 mm group indicated that they would request sedation if a further endoscopy were necessary, compared with 31% in the 9.8 mm group (P = 0.0005). Ultrathin endoscopes may have a role in clinical practice if randomized comparative studies with standard-bore instruments confirm that they do not compromise diagnostic quality.
    Endoscopy 04/2001; 33(4):311-6. DOI:10.1055/s-2001-13692 · 5.20 Impact Factor
  • Gastroenterology 04/2001; 120(5). DOI:10.1016/S0016-5085(01)82061-8 · 12.82 Impact Factor
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    ABSTRACT: Nonimmune mechanisms of mucosal defense seem to be biologically important and might explain the observed variability in the course of enteric infection in immunodeficiency. Mannose-binding lectin (MBL) deficiency is associated with persistent diarrhea in children. We found that genetic determinants of MBL deficiency appear to predispose to cryptosporidiosis in patients with the acquired immunodeficiency syndrome (AIDS), and went on to study interactions of MBL and complement on Cryptosporidium parvum sporozoites. This study involved cross-sectional study of MBL genotype and enteric infection in 72 Zambian AIDS patients with diarrhea, immunofluorescence analysis of MBL and C4 binding to C. parvum, and immunoblotting for MBL and complement in small intestinal fluid. Individuals homozygous for MBL structural gene mutations were at increased risk of cryptosporidiosis (odds ratio, 8.2; 95% confidence interval, 1. 5-42; P = 0.02). Lectin-mediated and concentration-dependent binding of purified MBL was detected on sporozoites but not oocysts, and MBL activated C4 on sporozoites. MBL, C3, C4, and albumin were detected in small intestinal fluid in half the patients tested, suggesting transudation of serum components into the enteropathic gut. The increased risk of cryptosporidiosis in MBL deficiency appears to include patients with AIDS. It may operate through MBL-mediated complement activation on sporozoites.
    Gastroenterology 12/2000; 119(5):1236-42. DOI:10.1053/gast.2000.19573 · 13.93 Impact Factor
  • R R Greaves, L J O'Donnell, M J Farthing
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    ABSTRACT: Nonsteroidal antiinflammatory drugs, inhibitors of prostaglandin synthesis, have different effects on gallbladder contractility in normal and diseased human gallbladders in vivo. We investigated this differential effect by comparing the effects of prostaglandins PGE2 and PGF2alpha, the thromboxane A2 mimetic U46619, and PGI2 on in vitro contractility in gallstone-free and gallstone-containing human gallbladders. Isometric tension was measured in gallbladder muscle strips mounted in organ baths. EC50 was calculated for each agonist. The rank order of potency in gallstone-free gallbladders was PGE2 > CCK > U46619 > PGF2alpha and in gallstone-containing gallbladders was U46619 > PGE2 > CCK > PGF2alpha. PGI2 produced contraction of gallstone-free gallbladder and relaxation of gallstone-containing gallbladder in the basal state. Further, PGI2 produced no relaxation in gallstone-free muscle strips precontracted with CCK, but significant relaxation in CCK precontracted gallstone-containing strips. PGE2, PGF2alpha, and U46619 are potent contractors of gallstone-free and gallstone-containing gallbladders, whereas PGI2 relaxes only gallstone-containing gallbladders. Since gallbladders containing cholesterol-supersaturated bile produce increased PGI2, this PGI2-induced relaxation may be a determinant of the impaired gallbladder motility of gallstone disease.
    Digestive Diseases and Sciences 12/2000; 45(12):2376-81. DOI:10.1023/A:1005624016268 · 2.55 Impact Factor
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    ABSTRACT: We report two cases of factitious diarrhoea caused by stool dilution. In the first report stools from a patient with chronic diarrhoea were found to have been diluted with urine, and the diarrhoea further compounded by surreptitious laxative misuse. In the second report, after prolonged investigation of high output ileostomy, the patient's ileal effluent was found to have been diluted with water. We conclude that factitious diarrhoea, in particular dilutional diarrhoea, is over-investigated and underdiagnosed. Stool weights, complete input/output measurement, analysis of stool osmolality and electrolytes, and laxative screening are essential in the investigation of chronic watery diarrhoea.
    European Journal of Gastroenterology & Hepatology 07/2000; 12(6):609-11. DOI:10.1097/00042737-200012060-00005 · 2.15 Impact Factor
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    ABSTRACT: Gum arabic (GA), a soluble fiber with emulsifying properties, enhances intestinal water and electrolyte absorption in normal and secreting rats. Our aim was to assess the effect of GA, 2.5 and 5.0 g/liter, on cholera toxin-induced water and electrolyte secretion in rat jejunum in vivo. After a 2-hr exposure to cholera toxin, jejunal segments of adult rats were perfused in vivo with at plasma electrolyte solution containing GA, 0, 2.5 or 5.0 g/liter. 24Na was used as a marker of sodium influx. Cholera toxin-induced secretion was reduced by GA, 2.5 and 5.0 g/liter. 24Na secretion into the lumen was reduced by GA. GA caused a morphological expansion of intercellular spaces in the villi but not crypts. In conclusion, GA promotes lumen to blood intestinal transport of water and sodium despite cholera toxin activation. These observations support a potential role for GA in enhancing the efficacy of ORS.
    Digestive Diseases and Sciences 06/2000; 45(5):946-51. DOI:10.1023/A:1005529209427 · 2.55 Impact Factor
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    ABSTRACT: The effects of Helicobacter pylori infection and its associated gastric histology on alpha-tocopherol and beta-carotene concentrations in serum, gastric juice and antral mucosa were investigated in patients undergoing routine gastroscopy for investigation of dyspepsia. Eighty-six patients were studied. High-performance liquid chromatography was used to measure alpha-tocopherol and beta-carotene concentrations. H. pylori infection was assessed by histology, bacterial culture, rapid urease test and serology. No obvious association was found between age, sex, smoking or endoscopic diagnosis and alpha-tocopherol or beta-carotene concentrations in serum, gastric juice and antral mucosa. However, alcohol drinkers had significantly lower antral mucosal and gastric juice beta-carotene concentrations compared to non-drinkers. Gastric juice beta-carotene concentration was markedly lower in patients infected with H. pylori than uninfected controls (2.9 nmol/l (interquartile range 0.3-4.3) versus 4.6 nmol/l (interquartile range 3.5-7.6), P = 0.01), but there was no significant difference in serum or gastric mucosal beta-carotene concentrations between the two patient groups. The presence of gastric atrophy and intestinal metaplasia was significantly associated with reduced mucosal alpha-tocopherol and beta-carotene concentrations. Furthermore, antral mucosal alpha-tocopherol concentrations decreased progressively as antral mucosal histology changed from normal to chronic gastritis alone and finally to atrophy and intestinal metaplasia. Gastric alpha-tocopherol and beta-carotene concentrations are affected by H. pylori-associated gastric histological changes, and these findings suggest that H. pylori infection may not only impair the protective role of vitamin C, but also of alpha-tocopherol and beta-carotene in the stomach.
    European Journal of Gastroenterology & Hepatology 06/2000; 12(5):497-503. · 2.15 Impact Factor
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    ABSTRACT: Linear growth retardation is a frequent complication of inflammatory bowel disease in children. The precise mechanisms causing growth failure are not known. To determine the relative contribution of reduced calorie intake and inflammation to linear growth delay and to determine the effect of inflammation on the hypothalamic-pituitary-growth axis. Linear growth was assessed in prepubertal rats with trinitrobenzenesulphonic acid (TNBS) induced colitis, in healthy free feeding controls, and in a pair-fed group (i.e. healthy animals whose daily food intake was matched to the colitic group thereby distinguishing between the effects of undernutrition and inflammation). Changes in length over five days in the TNBS colitis and pair-fed groups were 30% and 56%, respectively, of healthy free feeding controls. Linear growth was significantly reduced in the colitic group compared with the pair-fed group. Nutritional supplementation in the colitic group increased weight gain to control values but did not completely reverse the growth deficit. Plasma interleukin 6 (IL-6) concentrations were sixfold higher in the colitic group compared with controls. Plasma concentrations of insulin-like growth factor 1 (IGF-1) but not growth hormone (GH) were significantly lower in the colitic compared with the pair-fed group. Administration of IGF-1 to the colitic group increased plasma IGF-1 concentrations and linear growth by approximately 44-60%. It seems likely that approximately 30-40% of linear growth impairment in experimental colitis occurs as a direct result of the inflammatory process which is independent of undernutrition. Inflammation acts principally at the hepatocyte/IGF-1 level to impair linear growth. Optimal growth in intestinal inflammation may only be achieved by a combination of nutritional intervention and anticytokine treatment.
    Gut 06/2000; 46(5):694-700. · 13.32 Impact Factor
  • Gastroenterology 04/2000; 118(4). DOI:10.1016/S0016-5085(00)81534-6 · 12.82 Impact Factor
  • Gastroenterology 04/2000; 118(4). DOI:10.1016/S0016-5085(00)82297-0 · 12.82 Impact Factor
  • R C Pollok, M J Farthing
    Tropical Doctor 11/1999; 29(4):238-41. · 0.53 Impact Factor
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    ABSTRACT: Recent reports have suggested that intrasphincteric injection of botulinum toxin is effective and long-lasting in the treatment of achalasia. To report our experience of botulinum toxin injection in a prospective series of consecutive patients with achalasia. Eleven consecutive patients with achalasia (eight male, mean age 55 years, range 20-87) were treated with 60 units of botulinum toxin (Dysport; Speywood Pharmaceuticals Ltd, UK) into each of four quadrants at the lower oesophageal sphincter. Patients were assessed pre-treatment and 1 month after treatment using a symptom score and oesophageal manometry. Median follow-up was 12 months (range 6-28). The injection procedure was simple to perform and free of adverse effects. Although treatment had a beneficial effect on dysphagia (median pre-treatment score 3 [interquartile range 3-3]; post-treatment score 2 [0-3]: P=0.03) 1 month following therapy, there was no significant improvement in chest pain or regurgitation scores. Similarly, no significant reduction in median lower oesophageal sphincter pressure was observed (29.5 mmHg [21-42] pre-treatment, 28.5 [17.5-55.5] post-treatment P=0.67). Four patients (36%) required further therapy within 3 months and the overall relapse rate was 73% (eight of 11) within 2 years. Although botulinum toxin injection was well tolerated, these results using Dysport at a dose of 240 mouse units question its efficacy as a treatment for achalasia.
    Alimentary Pharmacology & Therapeutics 10/1999; 13(9):1221-5. DOI:10.1046/j.1365-2036.1999.00609.x · 5.48 Impact Factor
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    ABSTRACT: Much recent effort has been made to produce selective inhibitors of cyclo-oxygenase-2 (COX-2) in the belief that these will lack the gastrointestinal damaging effects of traditional non-steroidal anti-inflammatory drugs (NSAIDs). Inflammatory bowel disease is associated with increased local production of prostanoids. These prostanoids, particularly PGE2 and PGI2, may well be protective as inflammatory bowel disease is aggravated by NSAID use. To examine the effects of a traditional NSAID and a highly selective COX-2 inhibitor on the production of these prostanoids in human inflammatory bowel disease. Colonic mucosal biopsies were obtained from patients undergoing routine colonoscopy and biopsy for diagnostic or surveillance purposes. Biopsies were incubated in culture medium containing 10% foetal calf serum and antibiotics, plus test drugs or vehicle for 24 h, after which time the medium was removed and the content of PGE2, PGI2 (measured as 6 keto-PGF1alpha) and thromboxane (Tx) A2 (measured as TxB2) determined. Biopsies obtained from diseased colonic mucosa produced significantly more PGE2, PGI2 and thromboxane A2 than did controls (for example, PGE2: ulcerative colitis, 4.17+/-1.06; Crohn's disease, 3.97+/-1.66; control, 0.12 +/-0.13 ng/mL, n = 8-12). These increases were inhibited to a similar extent by either a highly selective COX-2 inhibitor (L-745,337) or a traditional non-selective NSAID (indomethacin). Until selective COX-2 inhibitors have been assessed adequately in human inflammatory bowel disease, these compounds should not be assumed to be safe for the gastrointestinal tract in inflammatory bowel disease.
    Alimentary Pharmacology & Therapeutics 09/1999; 13(8):1115-7. DOI:10.1046/j.1365-2036.1999.00585.x · 5.48 Impact Factor

Publication Stats

3k Citations
1,309.40 Total Impact Points

Institutions

  • 2005
    • St George's, University of London
      Londinium, England, United Kingdom
  • 1996–2004
    • University of Lusaka
      Lusaka, Lusaka, Zambia
    • Medical Research Council (UK)
      Londinium, England, United Kingdom
  • 2000
    • University College London
      • Institute of Child Health
      Londinium, England, United Kingdom
  • 1989–1999
    • St. Mark's Hospital
      Harrow, England, United Kingdom
  • 1998
    • Chris Hani Baragwanath Hospital
      Johannesburg, Gauteng, South Africa
  • 1997
    • University of Geneva
      • Department of Botany and Plant Biology
      Genève, GE, Switzerland
  • 1991
    • University of Cambridge
      Cambridge, England, United Kingdom
  • 1988
    • University of London
      Londinium, England, United Kingdom
  • 1986
    • Tufts Medical Center
      • Department of Medicine
      Boston, Massachusetts, United States
  • 1985
    • Harvard Medical School
      Boston, Massachusetts, United States