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Biomedical subjects

C L Walters

Publications and source records attributed to C L Walters.

At least 37 records · Page 2Linked to original sources
PubMed1987

Nitrosation of drugs under in-vivo conditions.

Application of the WHO Nitrosation Assay Procedure (NAP test) to a range of potentially nitrosatable drugs has given rise to considerable variations in the formation of volatile N-nitrosamines and N-nitroso compounds as a group. No nitrosation whatsoever was observed with 40 mM nitrite in some instances. In simulating more closely the conditions likely to be encountered in the human stomach, however, the order of susceptibility of the drugs to N-nitrosation has proved to be very different. At a constant nitrite concentration of 25 microM, which is considered to represent the upper limit of those likely to be encountered in the acidic human stomach, the drugs giving rise to the greatest yields of products reacting as N-nitroso compounds from a maximum adult dose were the penicillins, G, V, cloxacillin and ampicillin.

Chemical Phenomena↗
PubMed1986

The microflora of the gastric juice after Billroth I and Billroth II partial gastrectomy.

Detailed analyses of biochemical and microbiological variables such as pH, nitrite concentration, total viable counts (TVC), nitrate reductase-positive bacterial counts (NRPBC), and identification of microorganisms were carried out on 76 fasting gastric juice samples obtained at endoscopy from 64 patients previously submitted to partial gastrectomy (22 end-to-end Billroth I, 42 Billroth II/Reichel-Polya) and from 12 normal controls. Samples from normal controls were sterile, but bacteria were detected in the juice from all the operated patients. Significantly higher mean pH values and nitrite levels (p less than 0.001) were found in partial gastrectomies than in normal controls. In relation to surgical methods, higher mean pH values (p less than 0.005), nitrite levels (p less than 0.01), TVC (p less than 0.01), and NRPBC (p less than 0.005) were observed in the juice of patients with Billroth II as compared with Billroth I gastrectomies. Anaerobic bacteria, typical of faecal flora, and particularly Escherichia coli (p less than 0.05) characterized Billroth II samples. All these data suggest that the presence of bacteria in the gastric juice of gastroresected patients can be considered a risk factor of gastric neoplasia and that the type of operation used for the reconstruction of digestive continuity may influence the magnitude of this risk.

Adult↗
PubMed1985

Susceptibilities of drugs to nitrosation under simulated gastric conditions.

Drugs of differing structures and pharmacological actions have been incubated at 37 degrees C and pH 2.0 under conditions simulating those within the normal fasting stomach. The nitrite concentration (25 microM) was kept as constant as possible for 3 hr in an attempt to mimic its in vivo replenishment from the saliva. The extents of N-nitrosation varied widely, but were less than those observed by Gillatt et al. (Fd Chem. Toxic. 1984, 22, 269) using the WHO Nitrosation Assay Procedure, in which the initial nitrite concentration is 40 mM, 1600 times greater, and the pH (3.0) is close to the optimum for the N-nitrosation of secondary amines. The highest yield of N-nitroso compound was obtained with the benzathine salt of penicillin G whereas some drugs, including hydrochlorothiazide and chlorthalidone, produced no detectable N-nitroso derivative. The degree of N-nitrosation was consistently reduced when the initial nitrite concentration of 25 microM was not replenished during the incubations, underlining the importance of simulating the continuous supply of nitrite from the saliva. In all instances, the reactions of the drugs with nitrous acid were inhibited and, in most cases, completely prevented by the presence of ascorbic acid (125 mg).

Chemical Phenomena↗
PubMed1984

Intragastric bacterial activity and nitrosation before, during, and after treatment with omeprazole.

Ten healthy volunteers were studied before, during, and after treatment with omeprazole 30 mg daily for two weeks. On the 14th night mean nocturnal (2100-0700) intragastric acidity was significantly decreased by 75% (p less than 0.001). At 0700, 22 hours after the last dose of omeprazole, there were significant increases in the bacterial count and the nitrite and N-nitrosamine concentrations in the gastric juice (p less than 0.001). Three days later these changes had resolved. Short term treatment of healthy volunteers with omeprazole is associated with a short lived increase in the gastric bacterial flora, with endogenous production of N-nitroso compounds.

Adult↗
PubMed1984

Susceptibilities of drugs to nitrosation under standardized chemical conditions.

Of 22 drugs with either a N,N-dimethylamino, N,N-diethylamino or N-morpholino group in the molecule, eight were converted to volatile N-nitrosamines by nitrosative cleavage in reactions of nitrite and drug in a molar ratio of 4:1 at pH 3. Under standardized conditions yields were greatest with aminopyrine and minocycline which contains two N,N-dimethylamino groups in the molecule. Oxytetracycline, chlortetracycline, tetracycline, promethazine, chlorpromazine, imipramine and disulfiram gave much lower yields and amitriptyline, clomiphene, clomipramine, dextropropoxyphene, diphenhydramine, disopyramide, erythromycin, mepyramine, methapyrilene, penicillin G procaine salt, procaine, tamoxifen, trimeprazine and tripelennamine yielded no detectable levels of volatile N-nitrosamines. Nitrosation products of 57 drugs were also examined by a group selective procedure estimating both volatile and non-volatile N-nitroso compounds. Virtually all of the yield obtained from aminopyrine or minocycline could be accounted for by N-nitrosodimethylamine (NDMA). However, compounds yielding excess N-nitrosamines compared to NDMA were obtained from the other three tetracyclines, presumably as a result of the cleavage of a methyl group from the N,N-dimethylamino substituent to form desmethyl-N-nitroso compounds. In general, the drugs giving the highest yields of N-nitroso compounds were those containing secondary rather than tertiary amino groups. A considerable range of susceptibilities towards nitrous acid was observed overall; ten drugs containing a secondary or tertiary amino- or amido- or hydrazido - group did not react with nitrous acid to form N-nitroso compounds.

Chemical Phenomena↗
PubMed1984

Effect of H2 blockers on intragastric nitrosation as measured by 24-hour urinary secretion of N-nitrosoproline.

Intragastric nitrosation of proline (500 mg daily) was studied in eight volunteers and three duodenal ulcer patients. Daily urine outputs of N-nitrosoproline (NPRO) and N-nitrosothiazolidine-4-carboxylic acid (NTCA) were measured for two days before, two days during and two days after ingestion of H2 blocker (ranitidine). No increase in NPRO output was found with ranitidine, the trend being clearly towards decreased intragastric nitrosation of this amine. A significant (p less than 0.05) increase in NTCA occurred during H2 blockade, due to increased concentration of NTCA in urine. The biological significance of the presence of NTCA in urine is uncertain.

Adult↗
PubMed1984

The influence of enterogastric reflux on gastric juice bacterial growth, nitrite, and N-nitroso compound concentrations following gastric surgery.

Detailed analyses were carried out in 207 fasting gastric juice samples obtained at endoscopy or with a nasogastric tube from 50 patients with partial gastrectomy, 43 with vagotomy, 20 with gastric carcinoma and 50 controls. Significantly higher mean pH, nitrite and N-nitroso compound (N-NO) concentrations and nitrate-reducing bacterial cultures were noted following partial gastrectomy compared with normal controls and comparable to findings in gastric cancer. A highly significant relationship (p less than 10(-6)) was also demonstrated between pH and N-NO concentrations, highest levels of which were seen following Billroth II gastrectomy, significantly higher (p = 0.02) than Billroth I, whereas the only change observed following proximal gastric vagotomy was a nearly threefold rise in N-NO compared with normal controls. However, vagotomy and pyloroplasty produced gastric juice changes comparable to those seen with gastrectomy and gastric carcinoma. Thus, the most marked changes were observed following surgical procedures involving increased enterogastric reflux and these findings lend further support to the possible involvement of N-nitroso compounds in the development of gastric cancer following both Billroth I and II gastrectomy and vagotomy with pyloroplasty.

Carcinoma↗
PubMed1984

Pernicious anaemia, intragastric bacterial overgrowth, and possible consequences.

Intragastric bacterial colonization is well known in pernicious anaemia (PA), but its consequences have rarely been investigated. We have studied the clinical history, blood samples, and endoscopic biopsies from the stomach and duodenum of 80 patients with PA. In a random subgroup of 22 patients gastric juice was collected for aerobic culture and for estimation of nitrate, nitrate-reducing bacteria, nitrite, and N-nitrosamines; duodenal juice was studied in parallel in eight of these subjects. Gastric and duodenal juice had high bacterial counts; faecal organisms were found in 14 patients. The mean count of nitrate-reducing bacteria was significantly higher than in a control group of patients with peptic ulcer disease (p less than 0.001), as was the nitrite concentration (p less than 0.001). Thirty-three of the 80 patients had gastric dysplasias; 1 early gastric carcinoma was also found. Duodenitis was present in 39 out of 80 cases, in 6 associated with partial villous atrophy. A history of malabsorption and/or chronic intermittent diarrhoea was obtained significantly more often from patients with duodenitis. Four patients developed acute gastroenteritis shortly before or during the time of the study, two having a salmonella infection. Bacterial overgrowth in PA may be facilitated by altered immunological conditions, since low serum levels of IgA and IgG were found in this patient group.

Aged↗
PubMed1983

Intrathecal vincristine. Report of a fatal case despite CNS washout.

The clinical course of a two-year-old girl with acute lymphocytic leukemia (ALL) who inadvertently received intrathecal vincristine is presented. Despite aggressive treatment with parenteral folinic acid and extensive central nervous system washout, the outcome was fatal. The pharmacologic aspects of vincristine and folinic acid that may explain why treatment was unsuccessful, are reviewed.

Central Nervous System↗
PubMed1983

The formation of nitrite and N-nitroso compounds in salivas in vitro and in vivo.

The considerable differences in salivary nitrite levels observed previously in subjects who had abstained overnight from dietary nitrate as completely as possible were again found in tests on ten separate days. A 25-fold variation was observed in the rate of production of nitrite in vitro during the incubation of salivas from different subjects with 16 mM-nitrate under standardized conditions. N-Nitroso compounds were detected as a group on 11/100 and 14/100 occasions after incubations in vitro without and with added nitrate, respectively. No significant changes in salivary nitrite level were found 1 hr after the volunteers had ingested water-borne nitrate at approximately the World Health Organization recommended limit for continuous use (50 mg NO-3/litre), but increases in nitrite concentration were consistently found after volunteers ingested nitrate in water at four times this concentration. Although the nitrite concentrations were markedly increased following the intake of nitrate at the higher level, the occurrence of N-nitroso compounds in the salivas of the volunteers was greater immediately prior to the ingestion of water-borne nitrate than 1 hr afterwards.

Female↗