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R C Pollok

Publications and source records attributed to R C Pollok.

10 recordsLinked to original sources

Viruses causing diarrhoea in AIDS.

Opportunistic viral enteritis is an important gastrointestinal manifestation of HIV related disease. Cytomegalovirus (CMV) is a well established aetiological agent of disease in the gastrointestinal tract in this group. CMV enteritis may affect any region of the bowel, most commonly the colon. Diagnosis and management of these infections may be difficult. The role of other viruses in so-called 'pathogen-negative' diarrhoea remains controversial. The clinical importance of HIV-specific enteropathy is probably limited. Several viruses including astrovirus, picobirnavirus, small round structured virus and rotavirus have been implicated HIV-related diarrhoea. In addition, adenovirus has been linked to persistent diarrhoea in patients with a characteristic adenovirus colitis. The spectrum of disease morbidity and mortality amongst HIV patients has altered dramatically since the wide spread use of highly active antiretroviral therapy (HAART). Opportunistic infections, including CMV infection of the gastrointestinal tract in patients with AIDS, have diminished greatly. AIDS patients with CMV are able successfully to discontinue anti-CMV treatment without disease reactivation and with a parallel reduction in CMV viraemia following the initiation of HAART.

AIDS-Related Opportunistic Infections↗

Interferon gamma induces enterocyte resistance against infection by the intracellular pathogen Cryptosporidium parvum.

BACKGROUND & AIMS: Interferon (IFN)-gamma plays an important role in the immunologic control of infection by the protozoan enteropathogen Cryptosporidium parvum. We tested the hypothesis that IFN-gamma may directly inhibit infection of enterocytes by this pathogen. METHODS: HT-29, Caco-2, and H4 human enterocyte cell lines were grown in monolayers and incubated with IFN-gamma before exposure with C. parvum. IFN-gamma receptor expression in the cell lines was determined by Western blot analysis. RESULTS: IFN-gamma inhibited C. parvum infection of both HT-29 and Caco-2 cells but not H4 cells. Response to IFN-gamma was related to the expression of the IFN-gamma receptor in the respective cell lines. The effect of IFN-gamma was partially reversed by inhibition of the JAK/STAT signaling pathway. IFN-gamma mediated its action by at least 2 mechanisms: (1) inhibition of parasite invasion and (2) by modification of intracellular Fe(2+) concentration. No role for tryptophan starvation or nitric oxide synthase activity was found. TNF-alpha and IL-1beta also had anti-C. parvum activity but had no synergistic effect with IFN-gamma. CONCLUSIONS: IFN-gamma directly induces enterocyte resistance against C. parvum infection; this observation may have important consequences for our understanding of the mucosal immune response to invasive pathogens.

Animals↗

Enteric viruses in HIV-related diarrhoea.

HIV-related diarrhoea is an important cause of morbidity and mortality in HIV infection. Cytomegalovirus is a well-established cause of diarrhoea, but the role of other enteric viruses is less clear and will be discussed here. The clinical manifestations, disease mechanisms, diagnostic techniques and current treatments for the management of these infections are reviewed.

AIDS-Related Opportunistic Infections↗

Mannose-binding lectin is a component of innate mucosal defense against Cryptosporidium parvum in AIDS.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The increased risk of cryptosporidiosis in MBL deficiency appears to include patients with AIDS. It may operate through MBL-mediated complement activation on sporozoites.

Acquired Immunodeficiency Syndrome↗

Dilutional diarrhoea: under-diagnosed and over-investigated.

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.

Cathartics↗

Enteric viral infections as a cause of diarrhoea in the acquired immunodeficiency syndrome.

BACKGROUND AND AIMS: The role of non-cytomegalovirus (CMV) enteric viral infection in causing diarrhoea in patients with human immunodeficiency virus (HIV) is poorly understood. We aimed to investigate the prevalence of these infections in acute and chronic diarrhoea. METHODS: Stool specimens from 377 HIV-infected patients presenting with diarrhoea were studied prospectively for evidence of non-CMV enteric viral infection. Patients with diarrhoea underwent investigation for gastrointestinal pathogens, including electron microscopic examination of stool for enteric viruses. We collected data on patients in whom enteric virus was identified and examined the association of enteric virus infection with diarrhoeal symptomatology. RESULTS: Eighty-nine (10.3%) stool specimens from 60 (15.9%) HIV+ individuals were positive for coronavirus (n = 13, 22%), rotavirus (n = 11, 18%), adenovirus (n = 30, 50%) and small round structured viruses (n = 5, 8%) or dual infection (n = 2, 3%). Thirty-four of 52 (65%) patients available for analysis had acute diarrhoea, and 18/52 (35%) had chronic diarrhoea. Twenty-three of 52 (44%) patients had a concurrent gut pathogen. After exclusion of concurrent pathogens enteric viral infections were found to be significantly associated with acute as opposed to chronic diarrhoea (P = 0.004). The presence of adenovirus colitis was significantly more likely to be associated with chronic diarrhoea (15/21 cases) than adenovirus isolated from stool alone (9/23 cases) (P = 0.03). There was a trend towards an association between adenovirus colitis and colonic cytomegalovirus infection (P = 0.06). CONCLUSION: Enteric viral infection is strongly associated with acute diarrhoea in patients with HIV. Light microscopic examination of large bowel biopsies can identify adenovirus colitis which is significantly associated with chronic diarrhoea, and in addition may facilitate gastrointestinal co-infection with CMV.

AIDS-Related Opportunistic Infections↗