- Email: [email protected]
AMINOGLYCOSIDE RESISTANCE DUE TO MUTATION
856 has drawn attention to the study by Currie all which suggested that spironolactone, an aldosterone antagonist, prevents acute mountain sickness A.M.S.. The hypothesis upon which the use of spironolactone was based now seems vulnerable. Singh et al.3 suggested that people who got A.M.S. had fluid retention and, conversely, that a "Hohendiurese" on exposure to altitude augured well. I have suggested’ that aldosterone secretion increases at altitude in those who get A.M.S. and that this is causally related to the A.M.S. It seemed logical, therefore, to use an aldosterone antagonist to prevent A.M.s.’ There are difficulties with this hypothesis, however, because only one study has convincingly demonstrated an increase in aldosterone secretion at altitude." At least six others have demonstrated decreased aldosterone secretion.7-u In one study, when the severity of A.M.S. was assessed,13 plasma-aldosterone was significantly reduced, 12 and it was from this same location that the increased aldosterone secretion had previously been reported.6 Thus on balance it seems that aldosterone secretion decreases at altitude and that the hypothesis has been refuted. It would, therefore, seem unlikely that an aldosterone antagonist would be of use where plasma-aldosterone is already reduced. However, the study by Currie et al./ though largely anecdotal, does suggest that spironolactone can prevent A.M.S. If this effect is confirmed the mechanism might be by extrarenal mechanisms reducing cerebral acdema 14 and/or by spironolactone decreasing cerebrospinal-fluid secretion" via mechanisms unrelated to its aldosterone antagonism. Whatever new drugs become available to help the impatient climber to "bag his peak", they should always be combined with slow acclimatisa-
SIR,-Ramsay’
et
tion. University Medical Centre, Hamilton, Ontario, Canada L8S 4J9 McMaster
JOHN R. SUTTON
’
in this area, and this may well be true of man. The bronchi are, therefore, potential sites for hyperreactivity to stimuli and could produce excessive mucus and bronchoconstriction through the nervous mechanism. Such stimuli could, for example be air pollution, cigarette smoke, infections, cold air, or fog. Indeed, Widdicombe has lately discussed the1 hypothesis that allergic asthma might be nervously mediated.’ The investigation of apparently normal people to see if some of them have parasympathetic hyperreactivity and, if they have, the study of the relation of this to the subsequent incidence of disease might shed new light on chronic bronchitis. The Surgery, 18 Compton Avenue,
T. W. ASTIN
Luton, Bedfordshire LU4 9AZ
MULTIPURPOSE NEEDLE FOR GYNAECOLOGICAL SURGERY is not made easier by the wide variety of materials which the surgeon may use in a single operation. Trainees and theatre sisters are often confused about what has to be used to suture the various tissue
SIR,-Surgery
needles and
suture
layers. We have designed, in conjunction with a suture manufacturer, a multipurpose needle that can be used throughout most routine gynaecological operations. It has a 4 gauge U.S.P. halfcircle atraumatic needle with a diamond pointed clip attached to 0 ’Dexon’. The suture material is coloured green to make it easier to see. The simplification of having a single needle and suture material allows the operation to proceed more smoothly. Several gynaecologists at this hospital have found it satisfactory, and this approach may be of interest to general surgeons. The needle is available from Davis &
Geck Ltd., Fareham Road,
Gosport, Hampshire. BRONCHIAL HYPERREACTIVITY IN CHRONIC
Samaritan Hospital for Women, London NW1
R. W. BEARD
BRONCHITIS
SiR,—Iwould like to discuss one point arising from your excellent editorial on chronic bronchitis (Feb. 19, p. 403). I agree that the Dutch concept of bronchial hyperreactivity of an allergic type does not seem to be a factor in the causation of chronic bronchitis, but there is a danger that the concept of hyperreactivity might be lost altogether. There may well be a bronchial hyperreactivity of a non-allergic type. The bronchial tree is very sensitive, innervated by the parasympathetic system through the vagus nerve. Physiologists have shown that animals have many parasympathetic reflexes 1. 2. 3.
Ramsay, L. E. Lancet, 1977, i, 540 Currie, T. T., and others, Med. J. Aust. 1976, ii, 168. Singh, I., Khanna, P. K., Srivastava, M. C., Lal, M., Roy, S. B., Subramanyam, C. S. V. New Engl.
J. Med. 1969, 280,
175.
Sutton, J. R. Med. J. Aust. 1971, ii, 243. 5. Sutton, J. R., Lazarus, L. ibid. 1973, i, 545. 6. Frayser, R., Rennie, D. I., Gray, G. W., Houston, C. S. J. appl. Physiol. 1975, 38, 635. 7. Ayres, P. J., Hurter, R. C., Williams, E. S. Nature, 1961, 191, 78. 8. Slater, J. D. H., Williams, E. S., Edwards, R. H. T., Ekins, R. P., Sönksen, P. H., Beresford, C. A., McLaughlin, M. Clin. Sci. 1969, 37, 311. 9. Slater, J. D. H., Tuffley, R. E., Williams, E. S., Beresford, C. H., Sönksen, P. H., Edwards, R. H. T., Ekins, R. P., McLaughlin, M. ibid. p. 327. 10. Hogan, R. P., Kotchen, T. A., Boyd, A. E., Hartley, L. M.J. appl. Physiol. 1973, 35, 385. 11. Sutton, J. R., Viol, G. W., Gray, G. W., McFadden, M., Keane, P. M. ibid. (in the press). 12. Sutton, J. R., Rennie, D. I., Viol, G. W., Gray, G. W., Keane, P. M., Hous4.
ton, C. S. Unpublished. 13. Sutton, J. R., Bryan, A. C.,
Gray, G. W., Horton, E. S., Rebuck, A. S., Woodley, W., Rennie, D., Houston, C. S. Aviat. Space envir. Med. 1976, 47, 1032. 14. Schmiedek, P., Baethmann, A., Schneider, E., Brendel, W., Enzenbach, R., Marguth, F. Extrarenal Activity of Aldosterone and its Antagonists; p. 234. Amsterdam, 1972. 15. Davson, H., Segal, M. B.J. Physiol, Lond. 1970, 209, 131.
AMINOGLYCOSIDE RESISTANCE DUE TO MUTATION
SiR,-Dr Mawer and Dr Greenwood (April 2, p. 749) report isolates of a Providence strain and Pseudomonas ceruginosa. Although they did not test their isolates for the production of aminoglycoside-inactivating enzymes, we suggest that the development of resistance to gentamicin and other aminoglycosides was due to mutation. We agree with them that the Ps. aeruginosa isolated by Mr Amirak and his colleagues (March 5, p. 537) showed similar crossresistance to aminoglycosides (gentamicin, tobramycin, and amikacin); this resistance was probably due to mutation. Kanamycin acetyl-transferase is the only enzyme so far reported to inactivate amikacin, and it modifies, but does not significantly inactivate, gentamicin and tobramycin.2 The finding by Dr Mawer and Dr Greenwood of the development of resistance to gentamicin, tobramycin, and amikacin in a Providence strain exposed to gentamicin corresponds with our own. We colonised an in-vitro model ulcer with a sensitive strain of Ps. ceruginosa and then applied gentamicin cream to it; subsequent isolates showed resistance to gentamicin, tobramycin, and amikacin, in the absence of gentamicin acetylating or adenylating enzymes. Both tl.se experimental systems have selected mutants. We have studied3 gentamicin-resistant isolates of Ps. ceruginosa (13 from leg ulcers and 5 from ears affected by otius
aminoglycoside-resistant
1. 2. 3.
Widdicombe, J. G. Jl R. Coll. Physns, 1977, 11, 141. Benveniste, R., Davies, J. A. Rev. Biochem. 1973, 42, 471. Seal, D. V., Strangeways, J. E. M. Unpublished.
857
externa) and have found cross-resistance
to
tobramycin
and
amikacin in the absence of inactivating enzymes. Although these pseudomonads showed either a general growth defect or temperature sensitivity,’ they were isolated from patients considered to be infected. We are now studying 52 gentamicinresistant bacteria isolated from patients with septicaemia, meningitis, urinary-tract infection, and so on; 24 show resistance to
gentamicin, tobramycin, amikacin, neomycin,
paromomy-
kanamycin, and are considered to be mutants, whilst the remaining 28 show resistance to some but not all of these ammoglycosides, and fall into eleven different sensitivity patterns, eight of which are associated with known plasmidmediated inactivating enzymes. Aminoglycoside-resistance due to mutation is more common than is generally realised. Some of the mutants isolated after gentamicin therapy show highlevel gentamicin-resistance (highest minimum inhibitory concm,
and
The emergence of aminoglycoside resiscan be due to the selection either of mutants or of bacteria producing aminoglycoside-inactivating enzymes.’ We have isolated aminoglycoside-resistant mutants after gentamicin therapy lasting as little as 2 days (Ps. ceruginosa after intramuscular gentamicin 80 mg three times a day) and as long as 19 days (Klebsiella atlantce after daily intrathecal gentamicin). We have also isolated mutants from patients who have not been treated with gentamicin and must therefore have acquired their infecting organisms from the environment. Although we agree with others that mutants isolated in vitro are unstable, about 90% of our clinically isolated mutants are stable, when stored in Robertson’s cooked meat broth, for at least 6 months; one mutant, from a Ps. ceruginosa urinarytract infection treated with gentamicin, retained its resistance after storage on a nutrient agar slope for 8tyears. Aminoglycosides should be prescribed more rationally, and topical therapy should be discouraged; amikacin should be kept as a reserve antibiotic, but will have no effect on bacteria that have become aminoglycoside-resistant by mutation. centration tance
75[ig/ml).
during therapy
Public Health Laboratory, St George’s Hospital, London SW17
0.0625, spectinomycin 8, sulphamethoxazole and trimethoprim in the combination 19/1 3.8 and 0-2, and cefuroxime 0.03125. This is the first report of a &bgr;-Iactamase-producing gonococcus isolated in Belgium. The African origin of the strain is without doubt. The question remains whether &bgr;-Iactamaseproducing N. gonorrhcuce spontaneously emerged in Africa or has been imported there, and whether the plasmids of strains of geographically different origin are the same. Comparison with a strain from London (assumed to be imported from Ghanal) would be very interesting. There is an urgent need for investigating thoroughly the incidence of these strains in Africa, where very few data about antibiotic susceptibility of gonococci are available. Screening of N. gonorrhaeae isolates with the chromogenic cephalosporin 87/312 is a simple, economical, rapid and sensitive way to detect &bgr;-lactamase-producing gonococci in the clinical laboratory.
Laboratory of Bacteriology, Institute for Tropical Medicine, 2000
P. PIOT
Antwerp, Belgium
CIMETIDINE SUPPOSITORIES: ACID-SECRETION STUDIES IN DOGS
SIR,--Cimetidine, a histamine H2 receptor antagonist,3 has lately become available for treatment of peptic ulcer. Oral and intravenous cimetidine lowers gastric acid secretion in animals3 and man.45 However, patients with peptic ulcer often vomit or feel nauseated, and orally administered drugs may be tolerated. Since cimetidine has a similar action on gastric acid secretion in man and the dog3 we have measured the effect of rectally administered cimetidine on acid secretion in the canine stomach. not
D. V. SEAL J. E. M. STRANGEWAYS
RESISTANT GONOCOCCUS FROM THE IVORY COAST
S;R,—Ihave isolated
a
p-lactamase-producing
strain of
NeISseria gonorrhaeae from the urethral pus of a 28-year-old White heterosexual male. The day before the specimen was taken the patient had arrived from Yamoussoukro (Ivory Coast), where he had been infected by a local prostitute. He denied any sexual contact after his arrival in Belgium and until a negative urethral culture was obtained. He has been treated successfully with a single oral dose of rifampicin 900
mg by a private physician. The strain was isolated on
saponin-lysed blood agar with vancomycin-colistin-nystatin-trimethoprim inhibitor and proved to be a typical gonococcus (on colonial and gram stain morphology, oxidase positive, -galactosidase negative, and fermentation of glucose only). On screening for jj-lactamase production with the chromogenic cephalosporin 87/312,’ the test was positive, a result not previously recorded with nearly 200 strains of N. gonorrhocce. Minimum inhibitory concentrations mined with a plate dilution technique
(M.LC.S) were deterDST-agar (Oxoid
on
CM 261) containing 5% saponin-lysed horse blood and with an moculum of approximately 104 colony-forming units. The followmg M.i.c.s were found (in p.glml): benzylpenicillin 64,
ampicillin 64, tetracycline hydrochloride 1, erythromycin 4 Seal, D. V., Strangeways, J. E. M. Lancet, 1975, ii, 500. 5 Seal, D. V., Strangeways, J. E M. ibid. 1975, i, 48.
1 O’Callaghan, C. H., Morris, A., Kirby, S., Shingler, A. Chemother.
1972, 1, 283.
H. Antimicrob.
Ag.
in pH and transmucosal P.D. in Heidenhain after administration of cimetidine (C) rectally.
Changes
Mean :tS.E.M. for 8 experiments. There is and transmucosal P.D. (p<0-01).
a
significant
pouch
rise in
pH
(P<0-001)
8 experiments were done on two dogs. Cimetidine 400 mg in 15 ml of stock solution was administered rectally via a soft plastic cannula to anaathetised dogs with Heidenhain pouches which had been fasted overnight. Transmucosal potential difference (P.D.) and intraluminal pH in the pouch were monitored by methods described elsewhere." In both dogs the pH 2. Wkly epidem. Rec. 1976, 51, 385. 3. Brimblecombe, R. W., Doncoer, W. A. M., Durrant, G. S., Emmet, J. C., Gonellin, C. R., Parsons, M. E.J. int. med. Res. 1975, 3, 86. 4. Ivey, K. J., Geoffrey, G., Gaskin, W. Lancet, 1975, ii, 1072. 5. Pounder, R. E., William, J. G., Milton-Thompson, G. V., Misiewicz, J. J. Gut, 1976, 17, 133. 6. Khamis, B., Finucane, J., Doyle, J. S. Irish J. med. Sci. (in the press).
SIR,-Ramsay’
et
tion. University Medical Centre, Hamilton, Ontario, Canada L8S 4J9 McMaster
JOHN R. SUTTON
’
in this area, and this may well be true of man. The bronchi are, therefore, potential sites for hyperreactivity to stimuli and could produce excessive mucus and bronchoconstriction through the nervous mechanism. Such stimuli could, for example be air pollution, cigarette smoke, infections, cold air, or fog. Indeed, Widdicombe has lately discussed the1 hypothesis that allergic asthma might be nervously mediated.’ The investigation of apparently normal people to see if some of them have parasympathetic hyperreactivity and, if they have, the study of the relation of this to the subsequent incidence of disease might shed new light on chronic bronchitis. The Surgery, 18 Compton Avenue,
T. W. ASTIN
Luton, Bedfordshire LU4 9AZ
MULTIPURPOSE NEEDLE FOR GYNAECOLOGICAL SURGERY is not made easier by the wide variety of materials which the surgeon may use in a single operation. Trainees and theatre sisters are often confused about what has to be used to suture the various tissue
SIR,-Surgery
needles and
suture
layers. We have designed, in conjunction with a suture manufacturer, a multipurpose needle that can be used throughout most routine gynaecological operations. It has a 4 gauge U.S.P. halfcircle atraumatic needle with a diamond pointed clip attached to 0 ’Dexon’. The suture material is coloured green to make it easier to see. The simplification of having a single needle and suture material allows the operation to proceed more smoothly. Several gynaecologists at this hospital have found it satisfactory, and this approach may be of interest to general surgeons. The needle is available from Davis &
Geck Ltd., Fareham Road,
Gosport, Hampshire. BRONCHIAL HYPERREACTIVITY IN CHRONIC
Samaritan Hospital for Women, London NW1
R. W. BEARD
BRONCHITIS
SiR,—Iwould like to discuss one point arising from your excellent editorial on chronic bronchitis (Feb. 19, p. 403). I agree that the Dutch concept of bronchial hyperreactivity of an allergic type does not seem to be a factor in the causation of chronic bronchitis, but there is a danger that the concept of hyperreactivity might be lost altogether. There may well be a bronchial hyperreactivity of a non-allergic type. The bronchial tree is very sensitive, innervated by the parasympathetic system through the vagus nerve. Physiologists have shown that animals have many parasympathetic reflexes 1. 2. 3.
Ramsay, L. E. Lancet, 1977, i, 540 Currie, T. T., and others, Med. J. Aust. 1976, ii, 168. Singh, I., Khanna, P. K., Srivastava, M. C., Lal, M., Roy, S. B., Subramanyam, C. S. V. New Engl.
J. Med. 1969, 280,
175.
Sutton, J. R. Med. J. Aust. 1971, ii, 243. 5. Sutton, J. R., Lazarus, L. ibid. 1973, i, 545. 6. Frayser, R., Rennie, D. I., Gray, G. W., Houston, C. S. J. appl. Physiol. 1975, 38, 635. 7. Ayres, P. J., Hurter, R. C., Williams, E. S. Nature, 1961, 191, 78. 8. Slater, J. D. H., Williams, E. S., Edwards, R. H. T., Ekins, R. P., Sönksen, P. H., Beresford, C. A., McLaughlin, M. Clin. Sci. 1969, 37, 311. 9. Slater, J. D. H., Tuffley, R. E., Williams, E. S., Beresford, C. H., Sönksen, P. H., Edwards, R. H. T., Ekins, R. P., McLaughlin, M. ibid. p. 327. 10. Hogan, R. P., Kotchen, T. A., Boyd, A. E., Hartley, L. M.J. appl. Physiol. 1973, 35, 385. 11. Sutton, J. R., Viol, G. W., Gray, G. W., McFadden, M., Keane, P. M. ibid. (in the press). 12. Sutton, J. R., Rennie, D. I., Viol, G. W., Gray, G. W., Keane, P. M., Hous4.
ton, C. S. Unpublished. 13. Sutton, J. R., Bryan, A. C.,
Gray, G. W., Horton, E. S., Rebuck, A. S., Woodley, W., Rennie, D., Houston, C. S. Aviat. Space envir. Med. 1976, 47, 1032. 14. Schmiedek, P., Baethmann, A., Schneider, E., Brendel, W., Enzenbach, R., Marguth, F. Extrarenal Activity of Aldosterone and its Antagonists; p. 234. Amsterdam, 1972. 15. Davson, H., Segal, M. B.J. Physiol, Lond. 1970, 209, 131.
AMINOGLYCOSIDE RESISTANCE DUE TO MUTATION
SiR,-Dr Mawer and Dr Greenwood (April 2, p. 749) report isolates of a Providence strain and Pseudomonas ceruginosa. Although they did not test their isolates for the production of aminoglycoside-inactivating enzymes, we suggest that the development of resistance to gentamicin and other aminoglycosides was due to mutation. We agree with them that the Ps. aeruginosa isolated by Mr Amirak and his colleagues (March 5, p. 537) showed similar crossresistance to aminoglycosides (gentamicin, tobramycin, and amikacin); this resistance was probably due to mutation. Kanamycin acetyl-transferase is the only enzyme so far reported to inactivate amikacin, and it modifies, but does not significantly inactivate, gentamicin and tobramycin.2 The finding by Dr Mawer and Dr Greenwood of the development of resistance to gentamicin, tobramycin, and amikacin in a Providence strain exposed to gentamicin corresponds with our own. We colonised an in-vitro model ulcer with a sensitive strain of Ps. ceruginosa and then applied gentamicin cream to it; subsequent isolates showed resistance to gentamicin, tobramycin, and amikacin, in the absence of gentamicin acetylating or adenylating enzymes. Both tl.se experimental systems have selected mutants. We have studied3 gentamicin-resistant isolates of Ps. ceruginosa (13 from leg ulcers and 5 from ears affected by otius
aminoglycoside-resistant
1. 2. 3.
Widdicombe, J. G. Jl R. Coll. Physns, 1977, 11, 141. Benveniste, R., Davies, J. A. Rev. Biochem. 1973, 42, 471. Seal, D. V., Strangeways, J. E. M. Unpublished.
857
externa) and have found cross-resistance
to
tobramycin
and
amikacin in the absence of inactivating enzymes. Although these pseudomonads showed either a general growth defect or temperature sensitivity,’ they were isolated from patients considered to be infected. We are now studying 52 gentamicinresistant bacteria isolated from patients with septicaemia, meningitis, urinary-tract infection, and so on; 24 show resistance to
gentamicin, tobramycin, amikacin, neomycin,
paromomy-
kanamycin, and are considered to be mutants, whilst the remaining 28 show resistance to some but not all of these ammoglycosides, and fall into eleven different sensitivity patterns, eight of which are associated with known plasmidmediated inactivating enzymes. Aminoglycoside-resistance due to mutation is more common than is generally realised. Some of the mutants isolated after gentamicin therapy show highlevel gentamicin-resistance (highest minimum inhibitory concm,
and
The emergence of aminoglycoside resiscan be due to the selection either of mutants or of bacteria producing aminoglycoside-inactivating enzymes.’ We have isolated aminoglycoside-resistant mutants after gentamicin therapy lasting as little as 2 days (Ps. ceruginosa after intramuscular gentamicin 80 mg three times a day) and as long as 19 days (Klebsiella atlantce after daily intrathecal gentamicin). We have also isolated mutants from patients who have not been treated with gentamicin and must therefore have acquired their infecting organisms from the environment. Although we agree with others that mutants isolated in vitro are unstable, about 90% of our clinically isolated mutants are stable, when stored in Robertson’s cooked meat broth, for at least 6 months; one mutant, from a Ps. ceruginosa urinarytract infection treated with gentamicin, retained its resistance after storage on a nutrient agar slope for 8tyears. Aminoglycosides should be prescribed more rationally, and topical therapy should be discouraged; amikacin should be kept as a reserve antibiotic, but will have no effect on bacteria that have become aminoglycoside-resistant by mutation. centration tance
75[ig/ml).
during therapy
Public Health Laboratory, St George’s Hospital, London SW17
0.0625, spectinomycin 8, sulphamethoxazole and trimethoprim in the combination 19/1 3.8 and 0-2, and cefuroxime 0.03125. This is the first report of a &bgr;-Iactamase-producing gonococcus isolated in Belgium. The African origin of the strain is without doubt. The question remains whether &bgr;-Iactamaseproducing N. gonorrhcuce spontaneously emerged in Africa or has been imported there, and whether the plasmids of strains of geographically different origin are the same. Comparison with a strain from London (assumed to be imported from Ghanal) would be very interesting. There is an urgent need for investigating thoroughly the incidence of these strains in Africa, where very few data about antibiotic susceptibility of gonococci are available. Screening of N. gonorrhaeae isolates with the chromogenic cephalosporin 87/312 is a simple, economical, rapid and sensitive way to detect &bgr;-lactamase-producing gonococci in the clinical laboratory.
Laboratory of Bacteriology, Institute for Tropical Medicine, 2000
P. PIOT
Antwerp, Belgium
CIMETIDINE SUPPOSITORIES: ACID-SECRETION STUDIES IN DOGS
SIR,--Cimetidine, a histamine H2 receptor antagonist,3 has lately become available for treatment of peptic ulcer. Oral and intravenous cimetidine lowers gastric acid secretion in animals3 and man.45 However, patients with peptic ulcer often vomit or feel nauseated, and orally administered drugs may be tolerated. Since cimetidine has a similar action on gastric acid secretion in man and the dog3 we have measured the effect of rectally administered cimetidine on acid secretion in the canine stomach. not
D. V. SEAL J. E. M. STRANGEWAYS
RESISTANT GONOCOCCUS FROM THE IVORY COAST
S;R,—Ihave isolated
a
p-lactamase-producing
strain of
NeISseria gonorrhaeae from the urethral pus of a 28-year-old White heterosexual male. The day before the specimen was taken the patient had arrived from Yamoussoukro (Ivory Coast), where he had been infected by a local prostitute. He denied any sexual contact after his arrival in Belgium and until a negative urethral culture was obtained. He has been treated successfully with a single oral dose of rifampicin 900
mg by a private physician. The strain was isolated on
saponin-lysed blood agar with vancomycin-colistin-nystatin-trimethoprim inhibitor and proved to be a typical gonococcus (on colonial and gram stain morphology, oxidase positive, -galactosidase negative, and fermentation of glucose only). On screening for jj-lactamase production with the chromogenic cephalosporin 87/312,’ the test was positive, a result not previously recorded with nearly 200 strains of N. gonorrhocce. Minimum inhibitory concentrations mined with a plate dilution technique
(M.LC.S) were deterDST-agar (Oxoid
on
CM 261) containing 5% saponin-lysed horse blood and with an moculum of approximately 104 colony-forming units. The followmg M.i.c.s were found (in p.glml): benzylpenicillin 64,
ampicillin 64, tetracycline hydrochloride 1, erythromycin 4 Seal, D. V., Strangeways, J. E. M. Lancet, 1975, ii, 500. 5 Seal, D. V., Strangeways, J. E M. ibid. 1975, i, 48.
1 O’Callaghan, C. H., Morris, A., Kirby, S., Shingler, A. Chemother.
1972, 1, 283.
H. Antimicrob.
Ag.
in pH and transmucosal P.D. in Heidenhain after administration of cimetidine (C) rectally.
Changes
Mean :tS.E.M. for 8 experiments. There is and transmucosal P.D. (p<0-01).
a
significant
pouch
rise in
pH
(P<0-001)
8 experiments were done on two dogs. Cimetidine 400 mg in 15 ml of stock solution was administered rectally via a soft plastic cannula to anaathetised dogs with Heidenhain pouches which had been fasted overnight. Transmucosal potential difference (P.D.) and intraluminal pH in the pouch were monitored by methods described elsewhere." In both dogs the pH 2. Wkly epidem. Rec. 1976, 51, 385. 3. Brimblecombe, R. W., Doncoer, W. A. M., Durrant, G. S., Emmet, J. C., Gonellin, C. R., Parsons, M. E.J. int. med. Res. 1975, 3, 86. 4. Ivey, K. J., Geoffrey, G., Gaskin, W. Lancet, 1975, ii, 1072. 5. Pounder, R. E., William, J. G., Milton-Thompson, G. V., Misiewicz, J. J. Gut, 1976, 17, 133. 6. Khamis, B., Finucane, J., Doyle, J. S. Irish J. med. Sci. (in the press).