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S Leach

Publications and source records attributed to S Leach.

26 records · Page 2Linked to original sources

Nitrate and N-nitrosoproline excretion in two Italian regions with contrasting rates of gastric cancer: the role of nitrate and other factors in endogenous nitrosation.

Exposure to nitrate and propensity for endogenous nitrosation were examined in 80 healthy males, aged 25-40 years, residing in areas of Italy with long-standing high (Florence) and low (Cagliari) rates of gastric cancer. Nitrate exposure was assessed by measurement of urinary nitrate excretion over 12 hr, and endogenous nitrosation was assessed using the N-nitrosoproline test (NPRO-test). Our hypothesis was whether the geographic variation in cancer rate correlated with nitrate exposure or nitrosating ability. Exposure to background sources of NPRO was significantly higher in the high-risk subjects (phi = 0.04) whereas no differences were found in exposure to nitrate or in urinary NPRO levels after L-proline loading (test NPRO levels). The regional difference in test NPRO was almost completely accounted for by background NPRO exposure. Examination of individual rather than grouped data revealed that exposure to nitrate was a major factor in NPRO formation. No other factors studied (age, dietary-questionnaire-assessed intake of anti-oxidant vitamins) had a significant effect. Geographical variation in gastric cancer risk did not, therefore, correlate with either nitrate exposure or propensity for endogenous nitrosation of L-proline.

Adult↗

N-nitrosoproline excretion in the presence and absence of gastric disease.

N-nitrosoproline (NPRO) excretion, an indicator of endogenous nitrosation, was measured in a group of hospital inpatients who were identified by endoscopy and gastric biopsy as either having gastric lesions or having healthy stomachs. NPRO was assayed in background 24-hour urine samples and samples collected after loading doses of nitrate and L-proline. The presence of gastric lesions was associated with altered gastric pH and concomitant changes in gastric juice nitrate and nitrite concentration. Gastric juice pH increased with increasing severity of gastric disease (P = 0.031) and patients with normal stomachs had a lower gastric pH than those with chronic atrophic gastritis (CAG) (3.0 vs. 6.5, P = 0.017). The changes in gastric juice nitrate concentration were in the reverse direction (P = 0.002 for trend) with normal patients having higher mean levels than CAG patients (12.7 vs. 5.5 micrograms/ml, P less than 0.0001). Nitrite concentration increased with severity of gastric disease but the results were not significant (normal, 82.9 vs. CAG, 223.4 ng/ml, P = 0.069). No association was found between the presence of gastric lesions and increased urinary NPRO excretion. Mutagenic activity was not detected in any of the gastric juice samples.

Adult↗

Use of a modified N-nitrosoproline test to show intragastric nitrosation in patients at risk of gastric cancer.

Intragastric nitrosation has been implicated in the pathogenesis of gastric cancer and in precancerous conditions such as pernicious anaemia and the post-gastrectomy state. Intragastric nitrosation was assessed in at-risk patients by N-nitrosoproline (NPRO) excretion using both a conventional and a modified test. Twenty-four hour urinary excretion of NPRO was measured after oral administration of sodium nitrate (300 mg) and L-proline (500 mg) as an indirect indicator of intragastric nitrosation. In the conventional test no differences in intragastric nitrosation were found between at-risk patients and controls. In the modified test the loading dose of sodium nitrate was omitted and urinary NPRO levels were found to be significantly increased in Polya partial gastrectomy patients (P = 0.003) and post-vagotomy patients (P = 0.03) compared to controls. In pernicious anaemia patients NPRO levels were also higher than in controls but just failed to reach statistical significance. This study has confirmed that hypochlorhydria results in increased intragastric nitrosation, thus facilitating the formation of potentially carcinogenic N-nitroso compounds.

Adult↗

N-nitrosoproline excretion in patients with gastric lesions and in a control population.

N-Nitrosoproline (NPRO) excretion was measured in a group of hospital in-patients who were identified as either bearing gastric lesions or having apparently healthy stomachs. NPRO was assayed in background 24-h urine samples and then in urines collected after loading doses of nitrate and proline. The presence of gastric lesions was associated with altered gastric juice pH and nitrite concentration, but not with NPRO excretion. The significance of NPRO excretion as a marker of endogenous nitrosation is dependent on the interpretation of this result.

Adult↗

Adverse drug reactions: an investigation on an acute geriatric ward.

A total of 521 patients consecutively admitted to an acute geriatric unit were kept under surveillance by one observer during their stay. All drugs given to them and the occurrence of adverse events were recorded. One hundred and seventeen adverse drug reactions occurred in 94 patients representing 18.8% of the 500 patients receiving drugs. Thirteen of these reactions were considered severe. Each patient received an average of 6.1 drugs, not necessarily simultaneously. Altogether 212 different drug preparations were used. Diamorphine and insulin had the highest adverse reaction rates, diamorphine having the highest risk of a severe adverse reaction. Antibiotics and diuretics caused the most adverse reactions, and were by far the most commonly prescribed drugs (26.5% of the sample). Of the patients receiving eight or more drugs, 41% suffered an adverse drug reaction.

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Significant endogenous synthesis of nitrate does not appear to be a feature of influenza A virus infection.

There is much concern about the role of nitrate in the formation of carcinogenic N-nitroso compounds. There has been renewed interest in the endogenous formation of nitrate arising as a host response to infection. This study was designed to investigate whether the large increases in nitrate excretion rate reported (6-15-fold) for certain infectious diseases is also a feature of systemic influenza infections. Volunteers were challenged either with an attenuated strain of influenza A virus or with saline; and excreted nitrate was measured in subsequent 24-h urine samples. Both with and without adjustment for potential confounding by dietary and other factors, it was clear that neither mild nor moderate influenza A virus infection resulted in substantial endogenous nitrate biosynthesis since all the variation in urinary nitrate excretion observed was within the range of normal daily fluctuations. It remains possible that a stronger and more consistent nitrate excretion response might be observed in other infectious illnesses with greater systemic disturbance.

Adult↗