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Biomedical subjects

A Walan

Publications and source records attributed to A Walan.

At least 55 records · Page 3Linked to original sources

High gastric bile acid concentration in prepyloric ulcer patients.

The intragastric concentrations of bile acid (BAC) and pH were measured over 24 h in 13 patients with duodenal (DU), in 11 with prepyloric (PU) ulcer disease, and in 12 healthy controls. Large fluctuations in bile acid concentration occurred for individuals from all three groups. PU patients had BACs higher than DU patients and controls both during the day (p less than 0.01 and p less than 0.001) and at night (p less than 0.001 and p less than 0.05). Controls had a significantly higher BAC during the night than the day (p less than 0.001). The acidity was significantly higher in DU patients than in controls both during the day and night (p less than 0.05). Compared with PU patients, the DU patients had higher acidity at night (p less than 0.01).

Adult↗

Metabolic consequences of reduced gastric acidity.

A review of the effect on metabolism of antacids, anticholinergics and histamine H2-antagonists is given. It is stated that long-term treatment with antacids by a variety of mechanisms can cause severe metabolic complications such as the milk-alkali syndrome and phosphorus depletion. The interaction with other drugs can also be marked. There is very little known of the effect of anticholinergics on metabolism. Clinical experience has not indicated that any serious consequences will occur. The authors have investigated the effect continuous treatment with cimetidine 400 mg at night or twice daily for three years on weight, haemoglobin, plasma iron, plasma folate, plasma vitamin B12, albumin and plasma calcium. The only significant difference that occurred was a slight decrease of plasma calcium within the reference values. In conclusion it is stated that there is very little indication that the moderate and inconstant reduction of acidity over 24 hours which can be achieved by anticholinergics or twice daily administration of presently available H2-antagonists will result in metabolic consequences arising from reduced acidity. Higher doses given more frequently might give a risk for bacterial overgrowth with metabolic consequences.

Antacids↗

Prevention of ulcer recurrence--medical vs surgical treatment. The physician's view.

What factors should be considered in the choice between medical and surgical treatment of peptic ulcer disease? We would suggest the factors included in Table I. It is our opinion that we have concentrated too much on the recurrence rate, that is on how many of the patients who have a recurrence and not so much on the severity of recurrences in terms of symptoms, duration and influence on ability to work. It is also our firm belief that with regard to costs too much attention has been paid to one small part of the total cost, namely the cost for drugs. The strategy in the choice of the treatment for patients with a peptic ulcer depends on many factors as shown in Table II. At our department, the pharmacological part of the treatment of the first episode of an active duodenal ulcer as well as the first recurrences will usually consist of cimetidine 800 mg as a single nocturnal dose or in divided doses, for 4-6 weeks. Antacids are often given for relief of pain. The treatment will be continued for another 2 weeks if the patient is not symptomless after 4 weeks. The patient is then instructed to make further contact in the event of new symptoms suggesting a recurrence. Personally, we usually perform another endoscopy at that time as a guidance for the decision whether to give maintenance treatment or not. If we find an ulcer or signs of duodenitis, we give another 4-6 weeks course of cimetidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Cimetidine↗

Cimetidine or parietal-cell vagotomy in patients with juxtapyloric ulcers.

83 patients with severe juxtapyloric ulcers were randomly allocated to either long-term cimetidine treatment (400-800 mg/day) or to parietal-cell vagotomy (PCV). All were followed up for more than 3 years. The endoscopically proven relapse-rate with a dose of 400 mg at bed time was 54%; it fell to 32% when the dose was increased to 400 mg twice a day. In the PCV group the relapse-rate was 33%. Patients with prepyloric ulcers alone or in combination with duodenal ulcers relapsed at a higher rate (57% and 82%, respectively) than did patients with "pure" duodenal ulcer disease (17% and 14%, respectively). No patient, not even those with a history of bleeding or perforated ulcers, experienced any bleeding or perforation during relapses, either when on long-term cimetidine treatment or after operation. Previous haemorrhage or perforation per se is thus not an indication for surgery in favour of maintenance treatment with cimetidine.

Adult↗

Antacids and anticholinergics in the treatment of duodenal ulcer.

Anticholinergic agents are most often divided into tertiary and quaternary ammonium compounds. Tertiary ammonium agents are fully and rapidly absorbed. Quaternary ammonium agents are slowly and incompletely absorbed, but do not cross the blood-brain barrier, or do so to a very limited degree, and have a very low rate of central nervous system side-effects. There are probably subclasses of cholinergic receptors, and anticholinergic agents have different affinities for these. Anticholinergics can decrease the basal acid secretion as well as secretion stimulated by histamine, pentagastrin, insulin or food. Combined therapy with antacids and anticholinergics will give a more long-lasting decrease in acidity than with either drug alone. The reported controlled studies with anticholinergic agents suggest that they can induce healing of duodenal ulcer to the same degree as cimetidine but at the cost of more frequent side-effects. Except for the studies on pirenzepine there are, however, too few studies in which anticholinergics have been compared with histamine H2-receptor antagonists; thus the place of anticholinergics in the treatment of an active duodenal ulcer is not clear. In doses of not less than 100 mg daily, pirenzepine is a candidate-drug for the short-term treatment of duodenal ulcer. At these doses, side-effects of dry mouth and visual disturbance are, however, rather frequent, and more serious side-effects such as urinary retention do also occur. More studies with both the conventional anticholinergics and pirenzepine, with emphasis not only on the desired effects but also on side-effects, are needed before anticholinergics can be taken into consideration as alternatives to histamine H2-receptor antagonists for healing and maintenance treatment. There is some evidence that long-term treatment with anticholinergic agents can decrease recurrences and complications of peptic ulcer disease. Even if there are some encouraging reports on the combination of anticholinergics and antacids, we need more such studies with lower doses of antacids and lower doses of anticholinergics before this combination therapy can be regarded as an equally good alternative to histamine H2-receptor antagonists for ulcer healing and symptom relief.

Aluminum Hydroxide↗

Repeated pentagastrin-stimulated gastric acid secretory tests carried out in the evaluation of the pharmacodynamics of a new histamine H2-receptor antagonist, SK&F 93479.

Single doses of 10 mg or 20 mg intravenously or 25 mg or 40 mg orally of a new histamine H2-receptor antagonist, SK&F 93479, have been administered to 31 patients with peptic ulcer disease. BAO and MAO were measured before and repeated during a 26-h period after drug administration. In a separate group of 17 patients the mean coefficients of variation of BAO and MAO measured in this manner were 53% and 20%, respectively. If this variation in the placebo group is taken into account, BAO was significantly inhibited at all dose levels during the 3rd h after dosing, and a significant effect was still seen during the 25th h after 40 mg orally with a mean reduction of 77%. Mean inhibitions of MAO during the 4th h after dosing of SK&F 93479 were significant at all dose levels, and a significant effect could still be seen during the 26th h for the two oral doses. The mean inhibitions of MAO measured during the 4th and 10th h after dosing were after 10 mg intravenously 44% and 11%, after 20 mg intravenously 59% and 11%, after 25 mg orally 57% and 21%, and after 40 mg orally 75% and 46%. The percentage inhibition of MAO during the 10th h correlated with plasma concentrations (r = 0.64, p less than 0.01). SK&F 93479 is a potent inhibitor of acid secretion with a long duration of action.

Administration, Oral↗

Effect of omeprazole, a substituted benzimidazole, on 24-h intragastric acidity in patients with peptic ulcer disease.

Intragastric pH was measured during physiological conditions over 24-h periods in patients with peptic ulcer disease. After single oral doses of 20, 40, and 80 mg omeprazole we found a dose-dependent reduction in mean intragastric acidity ranging from 38% to 99%. After treatment for 1 week with omeprazole, 40 mg daily, with or without an initial loading dose of 80 mg, intragastric acidity was decreased by more than 99%. This is a more pronounced decrease in acidity than can be achieved even with very high doses of histamine H2-receptor antagonists.

Adult↗

Pharmacokinetics of oxmetidine, a new histamine H2-receptor antagonist, after single oral and intravenous doses.

The plasma concentration curves and urinary excretion of oxmetidine after administration of single i.v. (100 mg) and oral (200 mg) doses have been studied in 11 patients with peptic ulcer disease. The mean bioavailability of the drug was 70% (range 53-91%). After intravenous administration, the mean plasma t 1/2 beta was 3.0 h, the mean apparent volume of distribution 0.7 l/kg, the mean total plasma clearance 12.3 l/h and the mean plasma renal clearance was 0.7 l/h. Following intravenous and oral administration an average of 6% and 3%, respectively, of unchanged drug was found in the urine. The plasma concentration curve after oral administration in most patients exhibited two maxima, with peak concentrations appearing between 45 and 210 min after dosing.

Administration, Oral↗

Similar prevalence of coeliac disease in children and middle-aged adults in a district of Sweden.

Coeliac disease in children and adults is considered to be a variety of the same disorder. This gains epidemiological support in the present study, which reports on the observed prevalence of coeliac disease in an area of Sweden (population, 140 500). On 1 July 1981, the prevalence rate was found to be 104/100 000 (1:960) among children, and the same figure, 106/00 000 (1:950), was found for coeliac disease unaccompanied by dermatitis herpetiformis in the middle-aged population. The figures were obtained in patients seeking medical are and thus represent minimum rates, and it is likely that the actual prevalence of coeliac disease in Sweden will prove still higher.

Adolescent↗

Reversal of psychopathology in adult coeliac disease with the aid of pyridoxine (vitamin B6).

Signs of mental depression are typical in adults presenting with coeliac disease. The response to treatment was evaluated in 12 consecutive patients by means of the Minnesota Multiphasic Personality Inventory (MMPI), with surgical patients serving as controls. The coeliacs reported no change in depressive symptoms after 1 year's gluten withdrawal despite evidence of improvement in the small intestine. When retested after 3 years, however, after 6 months of 80 mg/day of oral pyridoxine (vitamin B6) therapy, they showed a fall in the score of scale 2 ('depression') from 70 to 56 (p less than 0.01), which became normalized like other pretreatment abnormalities in the MMPI. Cholecystectomy in the control subjects produced no alterations in the MMPI profile. The results indicate a causal relationship between adult coeliac disease and concomitant depressive symptoms which seems to implicate metabolic effects from pyridoxine deficiency influencing central mechanisms regulating mood.

Adult↗

Effect of cimetidine and oxmetidine on 24-h gastric acid and pepsin in patients.

The 24-h intragastric pH, titrated hydrogen ion concentration, and pepsin concentration were studied in nine peptic ulcer patients during administration of placebo and of 800 mg cimetidine given as two or four equal doses. Cimetidine, 400 mg twice daily, was more effective in reducing acidity during morning (p less than 0.05) and overnight (p less than 0.01) than cimetidine, 200 mg four times daily, which, however, was the most effective regimen during the afternoon (p less than 0.05-0.01). During the 24-h period pH values equal to or above 5 were observed for less than 1 h with placebo treatment, for 1.8 h with cimetidine, 200 mg four times daily, and for 4.7 h with cimetidine, 400 mg twice daily. A new histamine H2-receptor antagonist, oxmetidine, was studied in six other patients, also during a 24-h period. Both 400 mg twice daily and 200 mg four times daily of oxmetidine were superior to placebo (p less than 0.05) in reducing intragastric acidity during the entire 24-h period.

Adult↗

The pharmacokinetics of cimetidine and its sulphoxide metabolite in patients with normal and impaired renal function.

1 The pharmacokinetics of cimetidine and its sulphoxide metabolite was studied after a single intravenous dose of 200 mg cimetidine in nine patients with normal renal function and ten patients with severe renal failure on regular haemodialysis and during continuous oral cimetidine treatment in ten patients with normal renal function and 31 patients with different degrees of renal failure. 2 In normal renal function a mean of 47.3% of the single intravenous dose was excreted as unchanged drug and 12.8% as cimetidine sulphoxide. The mean plasma elimination half-life (T1/2) of cimetidine was 2.0 h and of cimetidine sulphoxide 1.7 h. 3 In severe renal failure a mean of 2.2% of the single intravenous dose was excreted as unchanged drug and 0.5% as cimetidine sulphoxide. The mean plasma T1/2 of cimetidine was 3.9 h. The plasma concentrations of the sulphoxide metabolite increased successively with time after dosing and no elimination phase was observed still 9 h after dose. The mean non-renal clearance of cimetidine was 210 ml/min and lower than in normal renal function, suggesting decreased metabolism of cimetidine in uraemia. 4 During continuous oral cimetidine treatment in patients with normal renal function and in patients g and no elimination phase was observed still 9 h after dose. The mean non-renal clearance of cimetidine was 210 ml/min and lower than in normal renal function, suggesting decreased metabolism of cimetidine in uraemia. 4 During continuous oral cimetidine treatment in patients with normal renal function and in patients g and no elimination phase was observed still 9 h after dose. The mean non-renal clearance of cimetidine was 210 ml/min and lower than in normal renal function, suggesting decreased metabolism of cimetidine in uraemia. 4 During continuous oral cimetidine treatment in patients with normal renal function and in patients with different degrees of renal failure given reduced doses of cimetidine the plasma concentrations of the sulphoxide metabolite were higher with decreasing renal function. The mean plasma T1/2 of cimetidine was 3.1 h in mild renal dysfunction (creatinine clearance 50-75 ml/min) and 4.5 h in severe renal failure (creatinine clearance 5-15 ml/min) and of cimetidine sulphoxide 5.3 and 14.4 h respectively. 5 Toxicity studies of cimetidine sulphoxide may be needed to assess if high plasma concentrations of the sulphoxide metabolite in severe renal failure are of clinical significance.

Administration, Oral↗

Cimetidine, but not oxmetidine, penetrates into the cerebrospinal fluid after a single intravenous dose.

1 Thirty-six patients with various neurological diseases or symptoms received single intravenous doses of either cimetidine 400 mg (n = 19) or oxmetidine 200 mg (n = 17), 15 or 60 min before a diagnostic lumbar puncture. 2 In the 15 min CSF samples concentrations of cimetidine were detectable but not measurable in 5 and non-detectable in 3 patients. 3 In the 60 min CSF samples the concentrations of cimetidine were detectable in all 11 patients and were measurable in 8 of these patients with a mean +/- s.e. mean of 0.12 +/- 0.01 microgram/ml. These CSF concentrations were correlated to simultaneously measured plasma concentrations (P less than 0.01). The mean ratio CSF/plasma concentration was 0.03. 4 No detectable concentrations of oxmetidine were found either in the 15 min (n = 9) or in the 60 min (n = 8) liquor samples. 5 Cimetidine penetrates the blood-drain barrier slowly and not freely after a single dose. Our data suggest that the new histamine H2-receptor antagonist oxmetidine does not cross this barrier.

Adult↗