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Biomedical subjects

C L Walters

Publications and source records attributed to C L Walters.

At least 55 records · Page 3Linked to original sources
PubMed1982

Association of bacteriuria and urinary nitrosamine formation with Schistosoma haematobium infection in the Qalyub area of Egypt.

In Egypt, bladder cancer incidence is high in areas where the prevalence and intensity of Schistosoma haematobium infection is also high. Experimental evidence shows bladder carcinogenesis to be a multi-stage process which can be accelerated by many factors. N-nitroso compounds, some of which are known bladder carcinogens, can be formed from amine precursors and nitrate in urine during some bacterial infections. In experimental animals the growth of nitrosamine-induced urothelial cancers is accelerated by damage to the urothelium caused by S. haematobium infections, and by analogy in man this could account for the lower peak age of incidence of this cancer in Egypt by comparison with Europe. The present study was designed to investigate whether bacterial infection of the urinary tract was common in areas of endemic schistosomiasis and whether N-nitrosamines were regularly found to be associated with bacteriuria. Urine samples from young men in the Qalyub area of Egypt and from an adjacent Delta region were analysed for S. haematobium ova, the nature and intensity of any bacterial infection, nitrate and nitrite, and total N-nitroso compounds plus volatile N-nitrosamines. A relatively high prevalence of bacteriuria was found in young men with schistosomiasis and low levels of N-nitroso compounds were present in all specimens. When the groups were sub-divided on the basis of the ability of their bacterial flora to reduce nitrate to nitrite (the latter is required for the nitrosation of amine precursors to N-nitroso compounds), significantly higher levels of N-nitroso compounds were found in S. haematobium-infected individuals also infected with nitrate-reducing bacteria by comparison either with uninfected controls (p less than 0.0005) or with those infected with non-nitrate-reducing bacteria (p less than 0.001). The results show N-nitroso compounds to be present in the urines of young men in areas of endemic S. haematobium infection in Egypt, and elevated levels of urinary N-nitroso compounds to be associated with infection of the urinary tract by various species of nitrate-reducing bacteria.

Adolescent↗
PubMed1982

Intragastric nitrites, nitrosamines, and bacterial overgrowth during cimetidine treatment.

A six week course of cimetidine (1 g/day) healed peptic ulcers in 20 of 23 patients (14 with duodenal ulcer, nine with gastric ulcer). Reduction of basal acid output by 73% and peak acid output by 36% led to a rise in concentrations of intragastric aerobic bacteria and nitrate-reducing bacteria. While the mean intragastric concentration of nitrate was unchanged by treatment, there were statistically significant rises in nitrite and N-nitrosamine concentrations. The conversion from nitrates to nitrites was closely related to the occurrence of nitrate-reducing bacteria. In three patients the intragastric milieu had returned to normal two months after cimetidine treatment had been discontinued. Mean nitrite and N-nitrosamine concentrations did not return to pre-treatment levels in the group of eight patients who remained on maintenance cimetidine (0.4 g at night-time) for three months after the full dose treatment. This study shows that cimetidine treatment can create an intragastric milieu resembling that of atrophic gastritis. Large scale and long-term studies are necessary to establish whether these findings have any clinical significance.

Adult↗
PubMed1982

N-nitroso compounds in gastric juice and their relationship to gastroduodenal disease.

Of the N-nitroso compounds derived from precursors in gastric juice, only a very small proportion are in the form of volatile N-nitrosamines. However, about 40% of the remainder can be converted by methylation into a form(s) suitable for gas chromatography. In this way, at least 20 individual peaks were detected with the Thermal Energy Analyzer as detector. N-Nitroso compounds have been determined as a group in the fasting gastric juice of normal individuals and patients with conditions including duodenal ulcer, gastric ulcer, atrophic gastritis, pernicious anaemia, gastric carcinoma, dyspepsia with normal endoscopy or subjected to operative procedures, such as vagotomy or partial gastrectomy. Both the levels of N-nitroso compounds and pH values increased significantly with age in normal subjects and in those with pathological conditions. Sex and cigarette smoking had no significant influence. In particular, a positive correlation was found between pH and the level of N-nitroso compounds, with a p value of less than or equal to 10(-6). Their concentration rose from a geometric mean of 0.11 mumol.1(-1) at pH 1.0-1.5, to a value of 1.3 mumol.1(-1) within the pH range 6.5-9.0. Whilst quantitative bacteriology was not carried out, a highly significant relationship was also observed between the concentration of N-nitroso compounds and the availability of nitrate-reducing bacteria. Thus, conditions conducive to gastric cancer are associated with higher levels of compounds responding to group analysis as N-nitrosamines and/or N-nitrosamides.

Adolescent↗
PubMed1981

Gastric juice N-nitrosamines in health and gastroduodenal disease.

The concentrations of total extractable N-nitroso compounds, pH, and nitrite levels were measured in fasting gastric juice, which was also cultured for bacteria, from 50 healthy volunteers and 217 patients with common upper gastrointestinal complaints. The concentrations of N-nitroso compounds and pH levels rose significantly with age. Sex and cigarette smoking had no significant effect. There was a positive correlation between pH and N-nitroso concentration, and between pH and an increase in the concentration of nitrites. A significant relation was demonstrated between raised N-nitroso and nitrite levels and growth of nitrate reductase-positive microorganisms. These results demonstrate for the first time in man the interrelations of N-nitrosamine concentration, pH, gastric juice nitrite, and nitrate-reducing bacteria. The findings are considered in relation to the risks of development of gastric cancer in man.

Adolescent↗
PubMed1981

Effect of cimetidine on gastric juice N-nitrosamine concentration.

Total extractable N-nitroso compounds, pH, and nitrite levels were measured in, and microorganisms were cultured from, the fasting gastric juice of 140 patients taking the H2-receptor antagonist cimetidine and from 267 subjects, including 50 healthy volunteers, not taking cimetidine. Significantly higher mean N-nitrosamine concentrations and pH levels were demonstrated in the cimetidine-treated patients; N-nitrosamine concentration increased with pH. In 30 patients studied, cimetidine treatment significantly increased gastric pH and N-nitrosamine concentrations, while in 23 patients withdrawal of cimetidine treatment resulted in a significant reduction of pH but not of N-nitrosamine concentrations. The gastric juice nitrite level was often raised and nitrate-reducing bacteria cultured were similar to those associated with other causes of hypochlorhydria. These results demonstrate for the first time a relation between gastric juice N-nitrosamine concentration, pH, and cimetidine treatment, and the findings are discussed in relation to gastric cancer induction.

Achlorhydria↗
PubMed1980

The exposure to humans to nitrite.

Although nitrate is more abundant than nitrite in food and the environment in general, it requires reduction by, for instance, bacterial or plant enzymes before it is involved in the nitrosation of amines or amides. Part of the exposure of humans to nitrite arises from its use as a food additive where it performs a very useful function in protecting the consumer from pathogenic micro-organisms such as Clostridium botulinum. Some untreated foodstuffs, such as potatoes, tomatoes and beets, also contain low levels of nitrite. Nevertheless, the main source of human contact is that produced in vivo from nitrate ingested in foods in general and in vegetables in particular. Nitrate also occurs widely in drinking water supplies and this source can also contribute in some measure to human exposure. As yet, it is not possible to compute with accuracy the contribution from any endogenous synthesis within the gastrointestinal tract. Since the rate of nitrosation of an amine is dependent on the nitrite concentration to a power of greater than unity, it is probable that nitrite ingested in one application over a short period will be more active in the synthesis of N-nitroso compounds than a continuous supply at lower concentrations over long periods.

Drinking↗
PubMed1980

The sequential determination of nitrite, N-nitroso compounds and nitrate and its application.

The selective determination of nitrite, N-nitroso compounds as a group and nitrate can be accomplished directly on most food or other matrices by quantifying the nitric oxide released following the additions in sequence of acetic acid, hydrogen bromide and titanous chloride under an atmosphere of nitrogen. Most of the many other compounds potentially formed from nitrite in a biological system are either decomposed to nitric oxide in the refluxing solvent system alone or else do not yield nitric oxide at any stage throughout the determinations of nitrite and N-nitroso compounds. Only nitrolic acids and S-nitrothiols, like nitrosamines and nitrosamides, require the use of hydrogen bromide for breakdown to nitric oxide. The application of the present procedure to the determination of nitrite and N-nitroso compounds (as a group) in a series of animal diets has shown the presence of levels of nitrite below the limit of detection of more conventional methods, even in those diets not deliberately treated with nitrite. Evidence was also obtained for the presence of non-volatile, non-extractable N-nitroso compounds in diets both treated and untreated with high levels of nitrite. Confirmation was provided in the case of one diet not treated with nitrite, in that it was found to convert morpholine into its N-nitroso derivative, which was detected by gas chromatography with a Thermal Energy Analyzer detector.

Animals↗
PubMed1980

Gastric bacteria, nitrate, nitrite and nitrosamines in patients with pernicious anaemia and in patients treated with cimetidine.

Patients with pernicious anaemia have a high risk of gastric cancer and we are investigating the role of N-nitroso compounds in their gastric carcinogenesis. We have carried out bacteriological studies and analyses of nitrite and N-nitroso compounds. Patients with duodenal or gastric ulcer are often treated with H2-receptor inhibitors such as cimetidine. This treatment induces hypochlorhydria similar to that in pernicious anaemia patients and it has been suggested that this might put these patients at risk of developing gastric cancer later. Analyses similar to those for p.a. patients have therefore been carried out in patients treated with cimetidine. We have set up an animal model of achlorhydria, using piglets, that will allow us to test in vivo the efficacy of compounds known to inhibit N-nitrosation in vitro. This is clearly necessary, in view of the growing size of the population now thought to be at risk.

Anemia, Pernicious↗
PubMed1980

Ultrasound detection of changing ventricular size in posthemorrhagic hydrocephalus.

Real time ultrasonography has been used to follow sequentially the changing size of the cerebral ventricles in an infant with posthemorrhagic hydrocephalus. A method for quantitating ventricular size is presented and the rapidity with which ventricular size decreases following removal of cerebrospinal fluid is demonstrated.

Cerebral Hemorrhage↗
PubMed1978

Determination of nitrite at low level without prior extraction.

A method has been devised for the determination of nitrite at low level that is directly applicable to food or other dried matrices without prior extraction. Nitric oxide released from nitrite through the action of acetic acid is determined using a chemiluminescence analyser. The limit of detection is approximately 0.02 microgram, the coefficients of variation being 5.7 and 8.2% using 0.1 and 0.05 microgram of sodium nitrite, respectively. The chemiluminescence analyser response is diminished when water in excess of 0.5 ml is present in the assay system unless hydrogen bromide in acetic acid is used instead of acetic acid alone. The application of the method to the direct determination of nitrite in freeze-dried cod fish has indicated a content of 0.25 mg NaNO2 per kg, equivalent to 0.050 mg per kg of the original undried material.

Animals↗
PubMed1978

Pathogenesis of gastric cancer in pernicious anaemia.

A pathogenetic mechanism to explain the increased incidence of gastric cancer in patients with pernicious anaemia (P.A.) is proposed. Mean nitrite concentration in gastric juice from thirteen fasting patients with P.A. was nearly fiftyfold greater than that of age-matched controls. The number of bacteria in the gastric juice of P.A. patients was also greatly increased. Small amounts of volatile nitrosamines were detected in simulated P.A. gastric juice in vitro, after addition of nitrite to achieve a concentration approximating to that found in vivo. If similar nitrosation occurs in vivo, the intragastric production of carcinogenic N-nitroso compounds could explain the high incidence of gastric cancer in patients with P.A.

Achlorhydria↗