- Email: [email protected]
CIMETIDINE ONCE DAILY
1354
weight, smoking and drinking habits, duration of disease,
and
antacid
consumption. 33 patients have been treated for 4 weeks (17 on twice daily cimetidine and 16 once daily) and 58 patients have been treated for 6 weeks (30 twice daily and 28 once daily). The healing rates for 4 weeks of treatment were 71% for the twice daily regimen and 75% for the once daily regimen. For 6 weeks the rates were 80% and 78%, respectively. There were no differences between the two groups in respect of numbers of days and nights with pain. We agree that cimetidine once a day (800 mg) can be as effective as cimetidine twice a day in healing the duodenal ulcer and in relieving pain.
Ospedale Valduce, 22100 Como, Italy
G. V. A. A. A. A. F. H.
MINOLI TERRUZZI FERRARA CASIRAGHI PRADA PORRO ROCCA RAINER
URTICARIA ASSOCIATED WITH CAMPYLOBACTER ENTERITIS Free thiol levels in
mixing experiments.
toxicity the drug has injection after cyclophosphamide or ifosphamide. Ifosphamide is also given by continuous infusion over 24 h (as three 8 h infusions); here mesna has to be infused at the same time, to maintain urinary levels of free thiol and so prevent haemorrhagic cystitis. Simply adding mesna to the ifosphamide infusion bag would be acceptable provided the two drugs do not react together. Several clinicians and pharmacists have telephoned us worried about the possibility of such a reaction, so we decided to investigate. The thiol group in mesna reacts with toxic oxazaphosphorine have to be maintained to prevent bladder to be given by frequent intravenous
mesna
metabolites, such
as
acrolein, chloroacetaldehyde, and
4-hydroxy-to oxazaphosphorines, that are present in the urine in the bladder, form stable thioethers of low toxicity. Reactions between other parts of the mesna molecule (eg, the sulphonate group) and oxazaphosphorine metabolites have not been reported and are unlikely on chemical grounds. If acrolein is added to mesna in vitro the free thiol groups decrease as the two molecules react to form a stable thioether (S03 Na CH2.CH2.SCH2.CHO). A similar reaction occurs between mesna and chloroacetaldehyde and between mesna and 4-hydroxycyclophosphamide (see figure). We have measured free thioethers after addition -of ifosphamide to mesna to see if reaction between ifosphamide and mesna in the coinfusion bag might reduce the availability of mesna and/or
ifosphamide. Mesna (1 .6 g/l) and ifosphamide (2 -6g/1) were added to dextrose saline in a polyethylene infusion bag; the solution was allowed to stand for 8 h at room temperature and samples were taken every hour and analysed for free thiols.2 Free thiol levels did not change in 7 h (see figure), suggesting that mesna and ifosphamide do not react in the infusion bag. Department of Clinical Pharmacology, University College London, London WC1
I. C. SHAW
J. W.P.ROSE
CIMETIDINE ONCE DAILY
SiR,-We can confirm the results of the multicentre trial described by Dr Delattre and Dr Dickson (March 17, p 625). In a double-blind trial coordinated at Valduce Hospital, Como, 91 patients with endoscopically proven duodenal ulcer seen at the Valduce, Legnano, Rho, Busto A, and Tradate hospitals were allocated to cimetidine (one 400 mg tablet plus one placebo tablet in the morning and another 400 mg cimetidine tablet at bedtime); 44 received one placebo tablet in the morning and two cimetidine tablets at bedtime. The groups were comparable for sex, age, body 1 Brock N Konzeption und wirkmechanisums von Uromitexan. Beitr Onkol 1980; 5: 1-11 2 Ellman GL. Tissue sulphydryl groups Arch Biochem Biophys 1959, 82: 70-7.
SIR,—We were interested to read the report by Dr Bretag and his p 954) of urticaria associated with enteritis. Besides the incident at the Sussex school referred to, there is the case, reported by M. J. Bradshaw and colleagues (Postgrad Med J 1980; 56: 80), of urticaria in a series of 109 patients with campylobacter enteritis studied in Chelmsford. We would like to report a further case. On Nov 9, 1983, a 2-year-old girl had fever (39 ° C), diarrhoea, and vomiting. 2 days later she was admitted to hospital with severe diarrhoea. Campylobacter jejuni biotype 1 was isolated from her stools. Her gastrointestinal symptoms subsided spontaneously during the next two days. On Nov 15 generalised urticaria suddenly developed (on the face, chest, arms, and legs) with oedema of her right eye. The rash could not be attributed to any specific antigenic stimulus such as a drug or food. She was given dexamethasone 2 mg and her rash disappeared within 4 h. She has since remained well. The link between campylobacter enteritis and urticaria is obscure. The urticaria is likely to be an idiosyncratic response; some strains of Cjejuni may be more likely to cause it than others. Since urticaria is often transient and mild, many cases may go unreported.
colleagues (April 28,
campylobacter
Department of Microbiology, Gran Hospital del Estado, Madrid 6; Spain and National Hospital for Infectious Diseases, Madrid
M. LOPEZ-BREA P. MARTIN FONTELOS M. BAQUERO L. ARAGON
51Cr-EDTA TEST FOR COELIAC DISEASE SIR,—Various techniques, based on probe markers of differing molecular weights, demonstrate an intestinal permeability defect in coeliac disease.The technology, time, and equipment for assay of most of these probes is available in research units only. A simple method, with chromium-51 labelled edetic acid (51 Cr-EDTA) as the probe, is described by Dr Bjarnason and colleagues.2 Advantages of this method over previous tests include patient acceptability, low cost, and rapid analysis on standard laboratory equipment. This technique was reported to show a high degree of sensitivity in defining the increased permeability in coeliac disease, both treated and untreated. Data (see figure) from two independent studies on Irish populations using the 51Cr-EDTA test as described by Bjarnason et al failed to distinguish controls from coeliac patients. Repeat testing showed poor reproducibility in some controls, none of whom were exposed to factors known to influence intestinal permeability, 1. Cobden
I, Rothwell J, Axon ATR Intestinal permeability and screening tests for coeliac disease. Gut 1980; 21: 512-18. 2. Bjarnason I, Peters TJ, Veall N. A persistent defect in intestinal permeability in coeliac disease demonstrated by a 51Cr-labelled EDTA absorption test Lancet 1983; i: 323-25.
weight, smoking and drinking habits, duration of disease,
and
antacid
consumption. 33 patients have been treated for 4 weeks (17 on twice daily cimetidine and 16 once daily) and 58 patients have been treated for 6 weeks (30 twice daily and 28 once daily). The healing rates for 4 weeks of treatment were 71% for the twice daily regimen and 75% for the once daily regimen. For 6 weeks the rates were 80% and 78%, respectively. There were no differences between the two groups in respect of numbers of days and nights with pain. We agree that cimetidine once a day (800 mg) can be as effective as cimetidine twice a day in healing the duodenal ulcer and in relieving pain.
Ospedale Valduce, 22100 Como, Italy
G. V. A. A. A. A. F. H.
MINOLI TERRUZZI FERRARA CASIRAGHI PRADA PORRO ROCCA RAINER
URTICARIA ASSOCIATED WITH CAMPYLOBACTER ENTERITIS Free thiol levels in
mixing experiments.
toxicity the drug has injection after cyclophosphamide or ifosphamide. Ifosphamide is also given by continuous infusion over 24 h (as three 8 h infusions); here mesna has to be infused at the same time, to maintain urinary levels of free thiol and so prevent haemorrhagic cystitis. Simply adding mesna to the ifosphamide infusion bag would be acceptable provided the two drugs do not react together. Several clinicians and pharmacists have telephoned us worried about the possibility of such a reaction, so we decided to investigate. The thiol group in mesna reacts with toxic oxazaphosphorine have to be maintained to prevent bladder to be given by frequent intravenous
mesna
metabolites, such
as
acrolein, chloroacetaldehyde, and
4-hydroxy-to oxazaphosphorines, that are present in the urine in the bladder, form stable thioethers of low toxicity. Reactions between other parts of the mesna molecule (eg, the sulphonate group) and oxazaphosphorine metabolites have not been reported and are unlikely on chemical grounds. If acrolein is added to mesna in vitro the free thiol groups decrease as the two molecules react to form a stable thioether (S03 Na CH2.CH2.SCH2.CHO). A similar reaction occurs between mesna and chloroacetaldehyde and between mesna and 4-hydroxycyclophosphamide (see figure). We have measured free thioethers after addition -of ifosphamide to mesna to see if reaction between ifosphamide and mesna in the coinfusion bag might reduce the availability of mesna and/or
ifosphamide. Mesna (1 .6 g/l) and ifosphamide (2 -6g/1) were added to dextrose saline in a polyethylene infusion bag; the solution was allowed to stand for 8 h at room temperature and samples were taken every hour and analysed for free thiols.2 Free thiol levels did not change in 7 h (see figure), suggesting that mesna and ifosphamide do not react in the infusion bag. Department of Clinical Pharmacology, University College London, London WC1
I. C. SHAW
J. W.P.ROSE
CIMETIDINE ONCE DAILY
SiR,-We can confirm the results of the multicentre trial described by Dr Delattre and Dr Dickson (March 17, p 625). In a double-blind trial coordinated at Valduce Hospital, Como, 91 patients with endoscopically proven duodenal ulcer seen at the Valduce, Legnano, Rho, Busto A, and Tradate hospitals were allocated to cimetidine (one 400 mg tablet plus one placebo tablet in the morning and another 400 mg cimetidine tablet at bedtime); 44 received one placebo tablet in the morning and two cimetidine tablets at bedtime. The groups were comparable for sex, age, body 1 Brock N Konzeption und wirkmechanisums von Uromitexan. Beitr Onkol 1980; 5: 1-11 2 Ellman GL. Tissue sulphydryl groups Arch Biochem Biophys 1959, 82: 70-7.
SIR,—We were interested to read the report by Dr Bretag and his p 954) of urticaria associated with enteritis. Besides the incident at the Sussex school referred to, there is the case, reported by M. J. Bradshaw and colleagues (Postgrad Med J 1980; 56: 80), of urticaria in a series of 109 patients with campylobacter enteritis studied in Chelmsford. We would like to report a further case. On Nov 9, 1983, a 2-year-old girl had fever (39 ° C), diarrhoea, and vomiting. 2 days later she was admitted to hospital with severe diarrhoea. Campylobacter jejuni biotype 1 was isolated from her stools. Her gastrointestinal symptoms subsided spontaneously during the next two days. On Nov 15 generalised urticaria suddenly developed (on the face, chest, arms, and legs) with oedema of her right eye. The rash could not be attributed to any specific antigenic stimulus such as a drug or food. She was given dexamethasone 2 mg and her rash disappeared within 4 h. She has since remained well. The link between campylobacter enteritis and urticaria is obscure. The urticaria is likely to be an idiosyncratic response; some strains of Cjejuni may be more likely to cause it than others. Since urticaria is often transient and mild, many cases may go unreported.
colleagues (April 28,
campylobacter
Department of Microbiology, Gran Hospital del Estado, Madrid 6; Spain and National Hospital for Infectious Diseases, Madrid
M. LOPEZ-BREA P. MARTIN FONTELOS M. BAQUERO L. ARAGON
51Cr-EDTA TEST FOR COELIAC DISEASE SIR,—Various techniques, based on probe markers of differing molecular weights, demonstrate an intestinal permeability defect in coeliac disease.The technology, time, and equipment for assay of most of these probes is available in research units only. A simple method, with chromium-51 labelled edetic acid (51 Cr-EDTA) as the probe, is described by Dr Bjarnason and colleagues.2 Advantages of this method over previous tests include patient acceptability, low cost, and rapid analysis on standard laboratory equipment. This technique was reported to show a high degree of sensitivity in defining the increased permeability in coeliac disease, both treated and untreated. Data (see figure) from two independent studies on Irish populations using the 51Cr-EDTA test as described by Bjarnason et al failed to distinguish controls from coeliac patients. Repeat testing showed poor reproducibility in some controls, none of whom were exposed to factors known to influence intestinal permeability, 1. Cobden
I, Rothwell J, Axon ATR Intestinal permeability and screening tests for coeliac disease. Gut 1980; 21: 512-18. 2. Bjarnason I, Peters TJ, Veall N. A persistent defect in intestinal permeability in coeliac disease demonstrated by a 51Cr-labelled EDTA absorption test Lancet 1983; i: 323-25.