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1.  Comparison of simple screening tests for fat malabsorption. 
Three tests were evaluated as screening procedures for fat malabsorption--namely, measurement of serum optical density, serum triglyceride concentration, and 14CO2 breath excretion after the administration of a 60 g fat meal containing 10 muCi glycerol tri[1-14C]oleate. The results of these tests were compared with fat excreted in a three-day faecal collection after adjustment for completeness of collection as assessed by using non-absorbable radio-opaque markers. Fifty-two patients with various symptoms and eight normal subjects were studied. The maximum increase in serum optical density or triglyceride concentration above the fasting value discriminated poorly between subjects with normal and increased adjusted faecal fat excretion. In contrast, seven- or eight-hour cumulative 14CO2 breath excretion provided good discrimination with only four (7%) false-positive and no false-negative results. The simplicity and convenience of breath analysis make it an attractive alternative to analysis of faecal fat excretion in screening for fat malabsorption.
PMCID: PMC1505440  PMID: 6786533
2.  Ability of SPI2 mutant of S. typhi to effectively induce antibody responses to the mucosal antigen enterotoxigenic E. coli heat labile toxin B subunit after oral delivery to humans 
Vaccine  2007;25(21):4175-4182.
We have evaluated an oral vaccine based on an Salmonella enteric serovar typhi (S. typhi) Ty2 derivative TSB7 harboring deletion mutations in ssaV (SPI-2) and aroC together with a chromosomally integrated copy of eltB encoding the B subunit of enterotoxigenic Escherichia coli heat labile toxin (LT-B) in volunteers. Two oral doses of 108 or 109 CFU were administered to two groups of volunteers and both doses were well tolerated, with no vaccinemia, and only transient stool shedding. Immune responses to LT-B and S. typhi lipopolysaccharide were demonstrated in 67 and 97% of subjects, respectively, without evidence of anti-carrier immunity preventing boosting of LT-B responses in many cases. Further development of this salmonella-based (spi-VEC) system for oral delivery of heterologous antigens appears warranted.
doi:10.1016/j.vaccine.2007.03.007
PMCID: PMC2652036  PMID: 17412462
Typhoid; Salmonella; Oral vaccine; ETEC; Enterotoxigenic E. coli
3.  Ability of SPI2 mutant of S. typhi to effectively induce antibody responses to the mucosal antigen enterotoxigenic E. coli heat labile toxin B subunit after oral delivery to humans 
Vaccine  2007;25(21-5):4175-4182.
We have evaluated an oral vaccine based on an Salmonella enteric serovar typhi (S. typhi) Ty2 derivative TSB7 harboring deletion mutations in ssaV (SPI-2) and aroC together with a chromosomally integrated copy of eltB encoding the B subunit of enterotoxigenic Escherichia coli heat labile toxin (LT-B) in volunteers. Two oral doses of 108 or 109 CFU were administered to two groups of volunteers and both doses were well tolerated, with no vaccinemia, and only transient stool shedding. Immune responses to LT-B and S. typhi lipopolysaccharide were demonstrated in 67 and 97% of subjects, respectively, without evidence of anti-carrier immunity preventing boosting of LT-B responses in many cases. Further development of this salmonella-based (spi-VEC) system for oral delivery of heterologous antigens appears warranted.
doi:10.1016/j.vaccine.2007.03.007
PMCID: PMC2652036  PMID: 17412462
Typhoid; Salmonella; Oral vaccine; ETEC; Enterotoxigenic E. coli
4.  Depletion of neuroendocrine cells in rectal biopsy specimens from HIV positive patients. 
Journal of Clinical Pathology  1992;45(6):524-527.
AIMS: To compare the density of neuroendocrine cells in rectal biopsy specimens from human immunodeficiency virus (HIV) infected individuals with that of a control group. METHODS: Neuroendocrine cells in rectal biopsies were identified using an immunohistochemical stain for chromogranin and subsequently quantified using a method of linear intercept. RESULTS: Neuroendocrine cells were found to be significantly decreased in the HIV positive group. CONCLUSIONS: Loss of neuroendocrine cells may contribute to apoptotic bodies seen in this condition. This could be related to infection of these cells with HIV and could contribute to diarrhoeal disease in HIV infection.
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PMCID: PMC495229  PMID: 1624601
5.  Ultrasonographic assessment of the extent of hepatic steatosis in severe malnutrition. 
Archives of Disease in Childhood  1992;67(11):1348-1352.
Ultrasonographic, blinded assessment was made of the extent of hepatic steatosis in 55 children with severe malnutrition: undernutrition (n = 6), marasmus (n = 18), marasmickwashiorkor (n = 17), and kwashiorkor (n = 14). The children were examined on admission, in early recovery (considered as baseline), and again at discharge. Eleven healthy control children and eight of the previously malnourished children were studied as comparison groups. Both oedematous and non-oedematous malnourished children had significantly more steatosis than the comparison groups at each time. Children with oedematous malnutrition had significantly greater steatosis than non-oedematous children at admission. Half of the non-oedematous malnourished children had appreciable hepatic steatosis at both admission and at baseline. Hepatic fat was only slowly mobilised. The rate constant was 1.4 +/- 0.3%/day. One quarter of the children did not change steatosis grades during the period they were in hospital. There was no overall correlation between the extent of steatosis and liver size. Hepatic steatosis in childhood malnutrition is not confined to oedematous children: it is frequently present in marasmic and undernourished children. Its extent is not necessarily related to the degree of hepatomegaly and accumulated lipid is only slowly mobilised.
PMCID: PMC1793750  PMID: 1471885
6.  Jejunal enteropathy associated with human immunodeficiency virus infection: quantitative histology. 
Journal of Clinical Pathology  1989;42(3):275-281.
Jejunal biopsy specimens from 20 human immunodeficiency virus (HIV) positive male homosexual patients were analysed and compared with those of a control group to determine whether the abnormalities were caused by the virus or by opportunistic infection. The degree of villous atrophy was estimated with a Weibel eyepiece graticule, and this correlated strongly with the degree of crypt hyperplasia, which was assessed by deriving the mean number of enterocytes in the crypts. The density of villous intraepithelial lymphocytes fell largely within the normal range, either when expressed in relation to the number of villous enterocytes or in relation to the length of muscularis mucosae. Villous enterocytes showed mild non-specific abnormalities. Pathogens were sought in biopsy sections and in faeces. Crypt hyperplastic villous atrophy occurred at all clinical stages of HIV disease and in the absence of detectable enteropathogens. An analogy was drawn between HIV enteropathy and the small bowel changes seen in experimental graft-versus-host disease. It is suggested that the pathogenesis of villous atrophy is similar in the two states, the damage to the jejunal mucosa in HIV enteropathy being inflicted by an immune reaction mounted in the lamina propria against cells infected with HIV.
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PMCID: PMC1141868  PMID: 2703544
7.  Hydrolysis of pyridoxal-5'-phosphate in plasma in conditions with raised alkaline phosphate. 
Gut  1980;21(3):192-194.
Hydrolysis of pyridoxal phosphate in plasma was demonstrated in patients with liver disease and other conditions with raised alkaline phosphatase, and this usually closely paralleled the alkaline phosphatase level, whether of liver or bone origin. The endogenous plasma pyridoxal phosphate was inversely related to the alkaline phosphatase, and plasma hydrolysis of pyridoxal phosphate may at least in part be responsible. Very large doses of vitamin B6 may be necessary to compensate for this hydrolysis.
PMCID: PMC1420355  PMID: 7399318
8.  AIDS in Africans living in London. 
Genitourinary Medicine  1995;71(6):358-362.
OBJECTIVES--To investigate the presentation of HIV infection and AIDS amongst Africans diagnosed with AIDS living in London. METHODS--Identification of all AIDS cases of African origin attending four HIV specialist centres in South London--Guy's, King's, St George's and St Thomas' Hospitals--up to March 1994, by retrospective review of case notes of all HIV positive patients. RESULTS--Of 86 patients (53 women, 33 men) studied, 59 (69%) were from Uganda. The most frequent AIDS-defining diagnoses were: Pneumocystis carinii pneumonia (PCP) 21%, tuberculosis (TB) 20% (extrapulmonary TB 14%, pulmonary TB 6%), cerebral toxoplasmosis 14%, oesophageal candida 13%, cryptococcal meningitis 11%, wasting 6%, herpes simplex infection > 1 month 5%, Kaposi's sarcoma 5%, other 6%. Cytomegalovirus retinitis was diagnosed in one case. Late presentation was common; 70% were diagnosed HIV positive when admitted to hospital. The diagnosis of AIDS was coincident with a first positive HIV test result in 61%. The mean CD4 counts at both HIV and AIDS diagnoses were similar in both men and women: 87 x 10(6)/l and 74 x 10(6)/l in men and 99 x 10(6)/l and 93 x 10(6)/l in women respectively. Overall, TB 21 (24%) (extrapulmonary TB 12, pulmonary TB 9) was either the AIDS-defining diagnosis or was detected within three months of this event. Sixty-two per cent of TB cases were diagnosed within twelve months of entry to the UK compared to 34% of all other AIDS cases. The prevalence of STD was very low; genital herpes was the commonest STD: 17% of the women, 9% men; 28% of the men and 11% of the women tested had a positive TPHA test. In cases known to be HIV-positive prior to an AIDS diagnosis, 41% took prophylaxis for PCP and 45% had taken zidovudine (ZDV). Forty two of the study participants had 89 children: 59 of these children had mothers in the study. Overall, 37 (42%) of the children had lost at least one parent at the time of data assessment. CONCLUSIONS--PCP and TB were the most common initial AIDS-defining diagnoses. The majority of TB cases were diagnosed within 12 months of entry to the UK. An AIDS-defining diagnosis was the first manifestation of HIV-related illness in the majority of patients. Because of late presentation to medical services, access to treatments for HIV infection and prophylaxis against opportunistic infections was limited. Extending the role of clinics and staff into the community might facilitate both earlier presentation and access to services. Future provision of local services will need to be sensitive to the requirements of individuals from different cultures and backgrounds.
PMCID: PMC1196104  PMID: 8566973
9.  Release of human immunodeficiency virus by THP-1 cells and human macrophages is regulated by cellular adherence and activation. 
Journal of Virology  1993;67(6):3569-3575.
Macrophage adherence, an important regulatory signal, has the potential to affect human immunodeficiency virus (HIV) production either directly or by priming monocytes to respond to other activating signals. We have investigated the role of adherence as an activator of HIV-1 transcription and release. The effects of adherence on HIV-1 transcription were examined by using THP-1 cells, a human monocytic cell line, transfected with HIV long terminal repeat (LTR)-chloramphenicol acetyltransferase (CAT) constructs. The effects of adherence on release of HIV-1 were investigated in both HIV-1-infected THP-1 cells and human peripheral blood monocyte-derived macrophages (MDM). Adherence of lipopolysaccharide (LPS)-stimulated THP-1 cells to either tissue culture plastic or endothelial cells was crucial for enhanced HIV-1 transcription as measured by LTR-CAT expression. Such increased LTR-CAT expression did not occur with an HIV LTR construct containing mutated NF-kappa B binding sites. In contrast, release of whole HIV, measured by reverse transcriptase (RT) activity in tissue culture medium, was reduced upon adherence of stimulated HIV-1-infected THP-1 cells without suppression of HIV LTR-CAT transcription or p24 release. This finding suggested that activation of adherent monocytic cells interfered with HIV assembly and release. Although the reduction of RT activity following activation of HIV-1-infected MDM was independent of adhesion, adherence alone of nonstimulated HIV-infected MDM to endothelial cells was sufficient to induce a reduction in RT release. This study demonstrates that LPS stimulation of monocytic cells enhances HIV LTR transcription under adherent conditions. In contrast, activation of adherent monocytic cells infected with HIV reduced viral release.
PMCID: PMC237704  PMID: 7684470
10.  Prolonged elevation of interleukin-8 and interleukin-6 concentrations in plasma and of leukocyte interleukin-8 mRNA levels during septicemic and localized Pseudomonas pseudomallei infection. 
Infection and Immunity  1992;60(6):2402-2408.
Patients suffering from serious bacterial infection present to the hospital after early inflammatory events, such as release of tumor necrosis factor (TNF), have been initiated. The role of other cytokines, such as interleukin-8 (IL-8), a neutrophil chemoattractant and activator, in the pathophysiology of human sepsis is not well characterized, and there are only limited data on IL-6. We studied serial concentrations of TNF, IL-6 (involved in the acute-phase response), and IL-8 in plasma and leukocyte levels of mRNA for these cytokines in patients with localized and septicemic Pseudomonas pseudomallei infection on admission to the hospital and during a prolonged recovery phase (up to 30 days). Of 18 patients, 8 had detectable plasma IL-8 and all had raised plasma IL-6 concentrations. In patients who died median initial concentration of IL-8 (167 pg/ml; range, 97 to 362 pg/ml) and IL-6 (4,800 pg/ml; range, 60 to 9,245 pg/ml) in plasma were higher than those in survivors (P less than 0.008 and P = 0.007, respectively). Septic patients who survived and patients with localized disease had similar cytokine levels. Plasma IL-8 and IL-6 concentrations were elevated throughout the inpatient period of recovery. Circulating leukocytes contained mRNA for IL-8 but not for IL-6 and TNF, and they may secrete IL-8. An elevated plasma IL-6 concentration (greater than 1,000 pg/ml) had 75% mortality) was the best predictor of mortality in P. pseudomallei sepsis. Fifty percent of patients with detectable plasma IL-8 concentrations died. In contrast, plasma TNF bioactivity did not relate to outcome; 75% of patients who did never had detectable plasma TNF activity.
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PMCID: PMC257173  PMID: 1375198
11.  Enteropathy associated with HIV. 
Gut  1990;31(8):960.
PMCID: PMC1378641  PMID: 2387528

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