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Biomedical subjects

J Holton

Publications and source records attributed to J Holton.

At least 19 recordsLinked to original sources

Spread of Neisseria meningitidis group A clone III-I meningitis epidemic into Zambia.

The epidemic of Neisseria meningitidis group A clone III-I strain began with the 1987 outbreak in Mecca, Saudi Arabia. Intense epidemics in African countries occurred the following year. Clone III-I was first isolated from Africa in 1988 in Chad, followed by epidemics in Ethiopia (1989), Kenya and Tanzania (1989), and The Central African Republic (1992). We report an epidemic of Neisseria meningitidis group A clone III-I afflicting Zambia during a 2-year period (April 1992-May 1994). This extension of the 'meningitis belt' southwards into Central Africa is cause for concern. Active surveillance for this disease should be carried out by all African countries, even those outside the well described sub-Saharan 'meningitis belt'.

Bacterial Typing Techniques

Clinical significance of Helicobacter pylori seropositivity and seronegativity in asymptomatic blood donors.

To determine the clinical significance of Helicobacter pylori seropositivity and seronegativity in healthy blood donors, we carried out a serological evaluation of Helicobacter pylori status and endoscopy in a healthy blood donors population. In all, 1010 donors were screened for Helicobacter pylori by IgG ELISA and assessed for pepsinogen I and gastrin levels by RIA; 298 IgG seropositive and 61 seronegative subjects underwent endoscopy with biopsies. Of 359, 165 were also tested for CagA by western blotting. Of the 298 IgG seropositives, 274 were shown to be infected on biopsy testing. Endoscopy revealed 70 peptic ulcers, 41 cases of erosive duodenitis, and two gastric cancers. In all 105 seropositive donors were tested for CagA and 69 were CagA positive [34/58 gastritis (58.6%), 24/35 duodenal ulcer (68.6%) and 11/12 gastric ulcer (91.6%)]. Histologically active/chronic gastritis was associated with CagA: 88.4% vs 50% (CagA seropositive vs seronegative). Of the 61 IgG seronegatives, 59 were negative on biopsy testing. At endoscopy three had duodenitis. Of the 60/61 IgG seronegatives tested for CagA, one had a moderate reaction. Duodenal ulcer donors showed higher pepsinogen I levels than donors without duodenal ulcers (97.7 microg/ml vs 80.9 microg/ml respectively). Screening for Helicobacter pylori and anti-CagA seropositivity and pepsinogen I can identify individuals likely to have gastroduodenal pathology even in the absence of symptoms.

Adolescent

Oral colonization is unlikely to play an important role in Helicobacter pylori infection.

BACKGROUND: This clinical and microbiological study investigated whether Helicobacter pylori colonizes the mouth en route to the pyloric antrum. It has been suggested that oral colonies are a source of reinfection after eradication of gastric infection. METHODS: Some 208 patients attending for routine diagnostic endoscopy for dyspepsia were recruited. Before endoscopy, samples were collected of saliva, supragingival and infragingival plaque, and swabs were taken from the tongue, mouth and pharynx. At endoscopy, gastric antral biopsies were taken for the rapid urease test, culture and histological examination. Gastric and duodenal juice samples were aspirated. Restriction nuclease digestion with HaeIII was employed on all specimens from patients in whom there was evidence of the organism in the mouth. RESULTS: H. pylori was observed in dental plaque in only 15 patients, all from the 116 who had evidence of the organism in the stomach. Restriction endonuclease digestion demonstrated that in 13 of the 15 patients the strains were identical in mouth and stomach. CONCLUSION: Oral colonization is a rare event, but does occur. Its rarity suggests that it is not an important factor in reinfection.

Dyspepsia

Blood tests in the management of Helicobacter pylori infection. Italian Helicobacter pylori Study Group.

There are three main types of blood test available for the management of Helicobacter pylori infection: those that detect an antibody response; tests of the pathophysiological state of the stomach; and those that indicate an active infection. Enzyme linked immunosorbent assay (ELISA) based kits are the most numerous of the commercially available tests. Originally the kits used crude antigen preparations but many of the newer kits use a more purified antigen preparation giving increased specificity but a lower sensitivity. The sensitivity, specificity, and predictive values of the tests can also be affected by the population under test and coexistent disease in the patients. Near patient test kits are based on either latex agglutination or immunochromatography. Generally, they have low sensitivities compared with laboratory tests. Commercial western blotting kits have also been developed and are used to detect the presence of specific virulence markers. The exact role of serology in the management of Helicobacter infection has still to be defined, although there is evidence that, used as a screening procedure, it can reduce endoscopy cost and workload. Gastrin and pepsinogen blood concentrations may provide valuable information on the pathophysiological state of the stomach--for example, the presence of inflammation or gastric atrophy. A combination of serology and serum concentrations of gastrin and pepsinogen may be used effectively to detect serious gastroduodenal disease in patients.

Antibodies, Bacterial

Helicobacter pylori: the mouth, stomach, and gut axis.

The aim of this study was to identify the natural reservoir and route of transmission of Helicobacter pylori infection. Two hundred eight (208) dyspeptic patients (114 males, 94 females; peak age of cohort, 50-59.9) were recruited. Specimens were collected from saliva, supra- and subgingival dental plaque, tongue scrapings, and oropharyngeal swabs. At subsequent endoscopy, gastric antral biopsy was performed for the rapid urease test (RUT), microbiological culture, and, in some patients, histology. Gastric juice samples were aspirated, and in 50 patients duodenal aspirate was collected. Polymerase chain reaction (PCR) with primers targeted to the 16S rRNA sequence of H. pylori was also employed for each of the specimens. In those patients where H. pylori was detected from multiple sites (dental plaque, gastric juice, gastric biopsy, and duodenal aspirate), restriction endonuclease digestion with Hae III was performed to determine if they were epidemiologically linked. The results indicated that 15/208 patients (7%) tested positively for H. pylori by PCR in dental plaque; only 2 samples were positive by culture. In none of the other oral sites sampled was H. pylori detected by any test used in the study. Gastric juice and gastric biopsy specimens from 36/ 208 patients (17%) and 114/208 patients (55%), respectively, were positive by PCR. Duodenal aspirate from 6/50 patients (12%) also tested positively by PCR. All specimens tested by restriction endonuclease digestion with Hae III (15/15 patients) were positive in both antral biopsy and gastric juice specimens, as well as 5 specimens from the duodenal aspirate. Four of the dental plaque strains had restriction patterns similar to those of the stomach and duodenal sites, providing evidence that these sites were infected with the same strain of H. pylori. In conclusion, the results suggest that H. pylori selects the gastric mucosa as its preferred site. The detection in dental plaque could indicate that the oral cavity may act as a reservoir or sanctuary for the organism. Whether H. pylori is a resident or transient oral microorganism is still unclear, although it is more likely to be transient in nature.

Bacterial Typing Techniques

Helicobacter pylori and diminished growth in children: is it simply a marker of deprivation?

Helicobacter pylori is an accepted gastroduodenal pathogen and has recently been investigated for possible implications in non gastroenterological diseases such as growth impairment coronary heart disease and diabetes. Infection by cytotoxic, i.e., CagA or VacA positive strains seems more likely to lead to more serious gastroduodenal diseases compared to infection by non cytotoxic strains, but the possible role of CagA or VacA positive strains in non gastroenterological diseases has not been investigated. Aim of the present study was to evaluate the prevalence of Helicobacter pylori infection as well as CagA and VacA positivity in three paediatric populations auxologically normal, hyposomic and diabetic children. Sera from a total of 522 children (auxologically normal: 246, hyposomic: 164, diabetic: 112) were analyzed by a novel Recombinant ImmunoBlot Assay-Strip Immunoblot Assay--RIBA SIA--which contain individual band for whole Helicobacter pylori lysate and recombinant CagA and VacA. The overall seroprevalence of reactivities against Helicobacter pylori lysate, CagA and VacA were: 7.3%, 9.3%, 6.9% vs 11.6%, 7.9%, 8.5% vs 14.3%, 13.4%, 8% (p = NS) in auxologically normal, hyposomic and diabetic children, respectively. Summarizing, we found a similar prevalence of reactivity against both whole Helicobacter pylori lysate as well as recombinant CagA and VacA between auxologically normal, hyposomic and diabetic children. Our data do not support a possible role of Helicobacter pylori in diminished growth in children.

Adolescent

Clinical relevance of culture: why, how, and when.

BACKGROUND: Culture for Helicobacter pylori is undertaken for research and industrial and diagnostic purposes, including antibiotic sensitivity testing of the isolate. The objective of this review is to evaluate the clinical relevance of culture for H. pylori. METHODS: The clinical relevance of culture for H. pylori is explored by a critical review of the literature. RESULTS: Primary isolation of the organism from specimens has direct clinical relevance in terms both of detecting colonization and of determining the antibiotic sensitivity of the isolate, which information is used for patient management and for local, national, or international prevalence rates and trends. It is suggested that when endoscopy is undertaken as part of a management algorithm, a biopsy should always be obtained for culture and sensitivity testing. H. pylori can be cultured from specimens on a variety of selective media, which are selected on the basis of the growth requirement of the organism. Standardization of culture media, culturing methods, and interpretive values for sensitivity testing of isolated strains is lacking. Culture of H. pylori on an industrial scale requires fermenter technology and media that maximize the production of bacterial products that can be easily purified and used as diagnostic or therapeutic agents. CONCLUSIONS: Culture of laboratory strains of H. pylori for investigation of the organism's metabolism and virulence factors has only indirect clinical relevance but has led to the identification of targets for therapeutic intervention.

Bacteriological Techniques

Serological response to Helicobacter pylori in gastric and non-gastric cancer.

1. We aimed to evaluate the seroprevalence of Helicobacter pylori (H. pylori) in gastric cancer, non-gastric cancer and outpatients by ELISA and iso-electric focusing, and to compare histology and serology for H. pylori in gastric cancer and outpatients. 2. In 124 patients with gastric cancer, 78 patients with non-gastric cancer and 110 outpatients, H. pylori seroprevalence was assessed by ELISA and isoelectric focusing. Gastric cancer and outpatients underwent endoscopy with biopsies. 3. Seroprevalence by ELISA was significantly higher in gastric cancer compared with non-gastric cancer (84% versus 56%, P < 0.001) but not with outpatients (84% versus 74%). Iso-electric focusing detection of H. pylori was comparable to ELISA: 85, 51 and 75% in gastric cancer, non-gastric cancer and outpatients respectively. Oligoclonal iso-electric focusing was significantly more frequent in gastric cancer compared with non-gastric cancer and outpatients: 69% versus 45 and 46% respectively, P < 0.01. The reliability of H. pylori detection by antral biopsy was significantly lower in gastric cancer compared with outpatients: 36% versus 74% (P < 0.001). In gastric cancer, ELISA and iso-electric focusing were significantly more reliable than histology in H. pylori detection (84 and 85% versus 36% respectively) (P < 0.001). 4. Serological immune response to H. pylori in gastric cancer, non-gastric cancer and outpatients seems different both quantitatively and qualitatively; serology was more reliable than histology in detection of H. pylori in gastric cancer.

Adult

The performance of a variable-flow indirect calorimeter.

Indirect calorimetry estimates energy expenditure from measurement of respiratory gas exchange volumes. This paper considers the design and evaluation of an indirect calorimeter, the Europa GEM, suitable for use in nutritional research. The calorimeter is of the ventilated hood, flow-through type and is intended for use with spontaneously breathing patients. Our aim was to develop an accurate, flexible instrument with a high level of automation. Performance was assessed in a laboratory simulation using reference gas injections (n = 24) producing a mean error of 0.3 +/- 2% in oxygen consumption (VO2), 1.8 +/- 1% in carbon dioxide production (VCO2) and 1.4 +/- 1.5% in respiratory quotient (RQ). In order to investigate the effect of FeCO2 on error multiplication a further subdivision (n = 8) of tests at FeCO2 = 0.5%, 0.75% and 1% was made by modulating the air flow through the hood. However, the predicted increase in system accuracy with increasing FeCO2 was not apparent in practice.

Calorimetry, Indirect

Community-based respiratory viral infections in HIV positive patients with lower respiratory tract disease: a prospective bronchoscopic study.

OBJECTIVES: To evaluate the contribution of community-based respiratory virus infections to lower respiratory tract disease in HIV-1 infected individuals. DESIGN: Prospective clinical cohort study. SETTING: Specialist in-patient unit for HIV and AIDS, University College London Hospitals, London. SUBJECTS: 44 consecutive HIV-1 antibody positive patients who underwent 47 diagnostic bronchoscopies for evaluation of the symptoms and signs of lower respiratory tract disease. TIME: Winter months of 1994/95. MAIN OUTCOME MEASURES: Detection, in bronchoscopic alveolar lavage fluid, of infection with influenza A and B, respiratory syncytial virus (RSV), parainfluenza 1, 2 and 3 (by immunofluorescence and cell culture) and adenovirus and enteroviruses (by cell culture). RESULTS: No evidence of influenza, RSV, parainfluenza, adenovirus, or enterovirus infection was detected. CONCLUSIONS: Despite a marked increase in RSV and influenza B infection in the general population over the winter of 1994-95, respiratory virus infections were not detected in this cohort of HIV infected patients. As the organisms causing lower respiratory tract disease were related to immunosuppression, this study questions the value of routine identification of community-based respiratory viruses in this patient group.

AIDS-Related Opportunistic Infections

Crusted ("Norwegian") scabies in a specialist HIV unit: successful use of ivermectin and failure to prevent nosocomial transmission.

A nosocomial outbreak of scabies in a specialist inpatient HIV unit resulted from a patient admitted with crusted scabies. Treatment of his infestation with topical scabicides alone failed and he remained infectious for several weeks. His infestation was then eradicated with combined topical treatment and oral ivermectin. In total, 14 (88%) out of 19 ward staff became symptomatic, and 4 (21%) had evidence of scabies on potassium hydroxide examination of skin scrapings. The ward infection control policy was changed to distinguish patients with crusted scabies from those with ordinary scabies. A second patient with crusted scabies was treated with combined oral and topical therapy early in his admission and nursed with more stringent isolation procedures. No nosocomial transmission occurred and his infestation responded rapidly to treatment. Patients with crusted scabies require strict barrier nursing if nosocomial transmission is to be avoided. Ivermectin combined with topical scabicides may be a more efficacious treatment than topical scabicides alone in such patients.

Adult

Gastric juice epidermal growth factor concentration and Helicobacter pylori in patients with duodenal ulcer.

The level of epidermal growth factor (EGF) was measured in the basal and maximally stimulated gastric juice of 20 control subjects and 20 patients each with duodenal ulcer and non-ulcer dyspepsia. Basal gastric juice was analysed for ammonia and urea concentrations, and the [ammonia]3/[urea] ratio was used to show Helicobacter pylori status, as was the [13C]urea breath test in nine controls. There was complete concordance in the nine controls between the two methods for determining H. pylori status. Twenty-five subjects were H. pylori positive (seven with duodenal ulcer, nine with non-ulcer dyspepsia, nine controls) and 35 H. pylori negative (13, 11 and 11 respectively). In H. pylori-positive subjects, the median EGF concentrations in the stimulated secretion of patients with duodenal ulcer and without (non-ulcer dyspepsia and controls combined) were 46.7 and 18.0 ng/ml (P < 0.001), and in H. pylori-negative subjects were 40.0 and 26.5 ng/ml respectively (P < 0.01). There was no difference in EGF concentration between controls and subjects with non-ulcer dyspepsia irrespective of H. pylori status. Lack of EGF is unlikely to be a cause of duodenal ulcer. The increased EGF concentration in patients with ulcer bore no relationship to the H. pylori status of the individual. If this bacterium causes duodenal ulcer, it is not via a reduction in EGF concentration.

Breath Tests

Helicobacter pylori status, endoscopic findings, and serology in HIV-1-positive patients.

We have carried out a large prospective study of the frequency of H. pylori infection and HIV-1 status in a community of ex-drug abusers including subjects with (N = 210) and without (N = 259) upper gastrointestinal symptoms, endoscopy and serology. Control groups were patients with upper gastrointestinal symptoms not at high risk of HIV-1 infection (N = 219) and asymptomatic blood donors (n = 322). H. pylori was present in 52% of symptomatic community residents having endoscopy and 55% of the control patients with symptoms but not at high risk of HIV-1 infection. H. pylori was less common in HIV-1-positive patients (40%) than those who were negative (66%; P < 0.001). In patients with AIDS (33%), the frequency of H. pylori infection was reduced compared to HIV-1-positive patients without AIDS (53%; P = 0.05). All the residents with AIDS had upper gastrointestinal symptoms. In community residents, peptic ulcer was always associated with H. pylori infection. By H. pylori serology, there was no difference in the frequency of infection in asymptomatic residents (56%) whether HIV-1 positive (55%) or HIV-1 negative (58%) compared with those residents with symptoms. Overall, H. pylori was less common in HIV-1-positive residents (49%) than those who were HIV-1 negative (61%; p < 0.05). This difference was due mainly to the low frequency of infection in residents with AIDS (33%). H. pylori infection is common in HIV-1 positive patients, and only slightly reduced when compared with at-risk HIV-1-negative subjects. Peptic ulcer is associated with H. pylori in HIV-1 infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome