Ammonium metabolism and protection from urease mediated destruction in Helicobacter pylori infection.

AIM: To investigate further the intracellular ammonium metabolism of Helicobacter pylori and the mechanism of its urease mediated destruction. METHODS: The mechanism of the in vitro destruction of H pylori was investigated by incubating it in buffer solutions, at pH 6.0, containing isocitrate or alpha ketoglutarate in addition to urea concentrations which had previously been shown to destroy H pylori. RESULTS: The median (range) 5 minute survival of H pylori in 0.2 mol/l citrate buffer (pH 6.0) in the absence of urea was 88% (18-184%) and was similar to its survival in 0.2 mol/l isocitrate buffer in the absence of urea, median 88% (15-274%). In the presence of 50 mmol/l urea the survival of H pylori in the citrate buffer was reduced, 9.9% (0-146%), compared with its survival in isocitrate buffer with the same concentration of urea 37% (0-274%) (p < 0.01). A 72 hour preincubation of the organism with 10 mmol/l alpha ketoglutarate also increased the 5 minute survival of the organism in 0.2 mol/l citrate buffer containing 50 mmol/l urea to 36% (9-145%) compared with its survival in the same buffer but without preincubation with alpha ketoglutarate 0% (0-62%). CONCLUSION: The protection of H pylori from rapid destruction by the supply of compounds used in the intracellular metabolism of the ammonium shows that the urease mediated destruction of H pylori can be explained by intracellular depletion of alpha ketoglutarate as a result of over production of ammonium by uncontrolled urease activity

The Urease Activity of Helicobacter pylori and Duodenal Ulcer Disease

Helicobacter pylori, a spiral shaped bacterium has recently been identified as one of the most important acquired factors in the development of duodenal ulcer disease. This organism colonises the gastric antral mucosa, the body of the stomach and areas of gastric metaplasia in the duodenum. Infection of the gastric mucosa by H pylori is associated with the development of type B gastritis, but also with the development of gastric ulcers, and more strongly with the development of duodenal ulcers. Almost 100% of individuals who have a duodenal ulcer have infection with H pylori. Eradication of H pylori infection of the antral mucosa is associated with a fall in basal plasma gastrin concentration, the meal stimulated gastrin response and gastric acid output suggesting that infection with H pylori could lead to increased gastric acidity and cause the development of duodenal ulcer disease. H pylori possesses unusually high urease enzyme activity. It has been suggested that the organism's urease activity could enable it to survive at low gastric pH by producing a cloud of ammonium which markedly raises the pH of the organism's environment and of the antral mucosal surface. The production of an alkaline microenvironment above the antral gastrin producing G cells could block the normal inhibition of gastrin release by gastric acid. An increased antral pH could also promote the uptake of amines which promote gastrin release. To examine the effects of infection on gastric ammonium concentration, plasma gastrin concentration and the creation of an alkaline microenvironment a series of studies were undertaken. The effect of infection by H pylori on the concentrations of ammonium and urea in gastric juice was investigated. The effect of stimulating and inhibiting urease activity on gastrin release was investigated. The effect of the alkalinisation of the gastric antrum on gastrin release was also investigated. The effect of urease activity on the survival of H pylori was also studied in a series of in vitro environments. Characteristic changes in the concentrations of ammonium and urea in gastric juice samples were demonstrated. In 27 subjects with duodenal ulcer disease the median (range) ammonium concentration was 3.4 mmol/L (1.0-13.0 mmol/L) when H pylori was present compared with 0.64 mmol/L (0.02-1.4 mmol/L) following eradication. In 16 subjects with chronic renal failure the median gastric juice ammonium concentration when infection was present was 20.0 mmol/L (13.9-43.1 mmol/L) compared with 4.8 mmol/L (0.5-12.3 mmol/L) when infection was absent. Gastric juice urea concentrations were lower when infection with the organism was present, median 0.8 mmol/L (0.5-2.9 mmol/L) compared with 2.1 mmol/L (1.0-3.7 mmol/L) after it had been eradicated. In subjects with chronic renal failure with infection the median gastric juice urea concentration was 2.2 mmol/L (0.5-8.7 mmol/L) compared with 13.8 mmol/L (5.4-20.8 mmol/L) when the organism was not present. The concentrations of urea and ammonium in the gastric juice samples did not clearly distinguish between the presence or absence of infection. When the urea/ammonium ratio was calculated all subjects with H pylori had a ratio of less than 0.8 while those free of infection had a ratio greater than 0.9. The urea/ammonium ratio could therefore be used to detect the presence of infection. The effect of stimulating and inhibiting urease activity, on the plasma gastrin concentration was studied. Urease activity was stimulated by the intragastric infusion of dextrose solution containing urea. Subjects with duodenal ulcer disease who had proven infection with H pylori were studied. The same subjects acted as their own controls following eradication of H pylori. The intragastric infusion of 50 mmol/L urea in a dextrose solution increased the median gastric juice ammonium concentration from 2.3 mmol/L (1.3-5.9 mmol/L) to 6.1 mmol/L (4.2-11.9 mmol/L). There was no change in plasma gastrin concentration observed during infusion of urea either before or after eradication of the organism. Inhibition of H pylori urease activity was also attempted. The specific urease inhibitor, acetohydroxamic acid was administered as a single 750 mg oral dose to 6 subjects who had duodenal ulcer disease. Inhibition of enzyme activity was demonstrated by the suppression of a 14C-urea breath test administered shortly after the dose of acetohydroxamic acid and reversion of the urea/ammonium ratio to that of non-infected subjects. No change in the basal plasma gastrin concentration or meal stimulated gastrin response occurred following inhibition of urease activity. Some investigators have failed to observe a rise in plasma gastrin concentration in response to alkalinisation of the gastric antrum. This could explain why stimulating and inhibiting urease activity failed to alter plasma gastrin concentrations. (Abstract shortened by ProQuest.)

Detroit's East Side Village Health Worker Partnership: Community-Based Lay Health Advisor Intervention in an Urban Area

In recent years, there have been few reports in the literature of interventions using a lay health advisor approach in an urban area. Consequently, little is known about how implementation of this type of community health worker model, which has been used extensively in rural areas, may differ in an urban area. This article describes the implementation of the East Side Village Health Worker Partnership, a lay health advisor intervention, in Detroit, Michigan, and notes how participatory action research methods and principles for community-based partnership research are being used to guide the intervention. Findings are presented on how the urban context is affecting the design and implementation of this intervention. Implications of the findings for health educators are also presented and include the utility of a participatory action research approach, the importance of considering the context and history of a community in designing a health education intervention, and the importance of recognizing and considering the differences between rural and urban settings when designing a health education intervention.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67390/2/10.1177_109019819802500104.pd

The white pine industry and the transformation of nineteenth-century Michigan

The white pine industry dominated the initial settlement and subsequent development of the northern two-thirds of the State of Michigan's Lower Peninsula. Between 1860 and 1910 northern Lower Michigan was transformed from forest to cutover; during this same period industrial technology was utilized increasingly to cut, transport, and mill white pine. This study is a historical geography of a nineteenth—century primary resource region. It investigates the geography of the Michigan white pine industry, and analyzes the geographical implications of industrialization. The evolving pattern of resource exploitation is examined, with detailed attention given to (1) environmental impact, (2) spatial organization, (3) patterns of land ownership, (4) scale of production, and (5) transportation of logs from stump to sawmill and of lumber from mill to market. Personal letters and diaries, newspapers, annual reports of government agencies, and account books and correspondence of lumber firms are used as primary data sources. The widespread adoption of technological innovations was found to have dramatically transformed the lumber industry during the late 19th century. In 1860 lumbering was a small—scale, seasonal industry based on human labor and water, wind, and animal power. By 1880 the scale of production had grown significantly, logging was less dependent upon seasonal rhythms, and steam power had increased the dependability of log transportation. A mechanized, rationalized, capital-intensive industry had emerged. Industrialization was found to have greatly enhanced the impact of lumbering on the landscape. Large contiguous tracts of timberland remained unbroken due to the growing scale of forest production and the frequent re—cutting of tracts. Logging became increasingly less selective as improved milling machines utilized smaller logs and woods other than pine. The use of railroads to haul logs and to supply camps extended the lumber economy throughout the region and facilitated the concentration of milling and wood manufacturing in lakeshore mill towns.Arts, Faculty ofGeography, Department ofGraduat

Nosocomial dysnatremia.

Abstract Patients who exhibited both hyponatremia and hypernatremia during a single admission were identified by a review of their biochemistry data. The mortality of patients who developed either hypernatremia or hyponatremia, followed by the opposite abnormality within less than or equal to 10 days, was 42%. This was greater than the 8.2% mortality for an age-, sex-, and admission-matched normonatremic control group (P less than 0.01, chi 2). Eight of the 10 patients who died had had a change in the sodium concentration in serum greater than 20 mmol/L. The interval (days) between the maximum and minimum sodium concentrations in the survivors and those who died was not statistically different. We found no specific clinical features that could be used to predict the development of this biochemical abnormality.</jats:p

Medical Training in Clinical Biochemistry (Chemical Pathology) in Scotland 1985–1989

A questionnaire was sent to 35 doctors who were believed to have trained in clinical biochemistry in Scotland between 1 January 1985 and 31 December 1989. Thirty replies were received from 23 individuals who were still employed in the speciality (including seven consultants and nine senior registrars) and from seven individuals who had left. Twenty considered that training within the laboratories in which they were employed had not been satisfactory. The main emphasis of training was directed towards reporting duties, clinical liaison, research, teaching and outpatient clinics. Little training was provided for the development of analytical experience, personnel selection and laboratory management. Those surveyed identified poor training in laboratory management as the main aspect of training which required improvement. </jats:p