- Email: [email protected]
R FACTORS AND ANTIBIOTIC USAGE
961
bradykinin in the gut wall, and 5-H.T., gastrin, cholecystokinin, secretin, and angiotensin in the blood. High blood-levels of 5-H.T. in the carcinoid syndrome probably cause the diarrhoea of that disease, and cholecystokinin can reproduce, in patients with irritable bowel, the contractions and pain of the syndrome 1; but for the other substances the evidence that they are involved in disorderly gut movement is scanty. And if they are, it might be indirectly-for example, by affecting smooth muscle in blood-vessels rather than in gut wall, or by affecting ganglionic relays. Disorderly motility at any level means one of four things: increased propulsion (diarrhoea); diminished propulsion (achalasia of the cardia, delayed gastric emptying, ileus, constipation); retropulsion (vomiting and duodenogastric reflux); or excessive contraction (colic, diverticular disease, irritable-bowel syndrome). Of all of these the irritable-bowel syndrome is probably the most troublesome diagnosis to make, since it can only be reached by lengthy and comprehensive exclusion of structural gut troubles. The pain is usually in the left iliac fossa, but it may be anywhere in the belly, and there is usually increased frequency of bowel opening and painful postprandial distension. Like other recurrent abdominal complaints it is often associated with psychiatric troubles. A source of bulk in the diet and an anticholinergic drug or mebeverine are helpful. In support of Burkitt’s dietary-fibre hypothesis, Hodgson2 has found high intracolonic
stance
P and
pressures in rabbits fed on a low-residue diet. Such pressures are seen in irritable-bowel syndrome and may eventually lead to diverticular disease. Amitrip-
tyline and other tricyclic antidepressants possibly have a direct action on the bowel. There is need for a specific test for the irritable-bowel syndrome; it would save much time and money. The mouthto-anus transit-time and the 24-hour faecal weight are easily measured but are not very helpful. Only specialised centres can mount tests such as gastricemptying time, small-intestinal transit, colonic propulsive mass movements, or non-propulsive
segmentation. A great deal has been learned from intraluminal Under experimental conpressure measurements. ditions, gut contractions have been recorded so fierce that intraluminal pressures exceeded arterial bloodpressure. Yet they were completely painless. This suggests that the painful colic in smooth-muscle spasm is not due to gut-wall ischoemia. Diarrhoea, of course, is usually a symptom of structural disease of the gut, but in a proportion of patients it is explicable only as a disorder of function. Most treatments are symptomatic-little is known about how they act. Paradoxically, rational treatment is available for the rare patient with carcinoid syndrome, where diarrhoea due to excess circulating 5-H.T. is often controllable by the
specific antagonist methysergide. Constipation is the other main disorder of colonic motility, but here, too, simple questions remain unanswered. What is the consistency of a normal human stool ? In this should we more resemble cows or rabbits ? What, indeed, is constipation ? 1. 2.
Harvey, R. F., Read, A. E. Gut, 13, 837 (abstr.). Hodgson, J. ibid. p. 838 (abstr.).
Regular laxative-taking increases with age, from about 10% in the 20-30 year age-group, to over 50% in those over 60. A moral tone is often wrapped up in laxative habituation, users speaking about a good clearout or a brisk purge, as though the artificial production of diarrhoea had some innate puritanical virtue. Some patients are started on the laxative habit in hospital, and the resultant loss of normal bowelopening rhythm can be a serious matter for disabled people, who become afraid to leave home if they are subject to urgent calls to stool. Of the various classes of laxatives most, such as bulk additives, osmotic expanders, and stool lubricants, are harmless. But the anthroquinone group, which includes the popular senna, are strong cell poisons when given parenterally. They are effective in small oral doses, but there is good reason to believe that they damage the gut wall if taken habitually. In the laxative-abuse syndrome, ever-increasing amounts are taken by the addict, whose colon is eventually converted into a passive tube incapable of peristalsis. The only treatment may be colectomy. Yet there is very little supervision of laxative-prescribing in hospitals. Nurses, who them be much more should aware of most, prescribe their serious side-effects and addictive properties.
R FACTORS AND ANTIBIOTIC USAGE THE problems of controlling resistant gram-nega-
tive infections in hospital have proved even more complex and elusive than the control of resistant
staphylococci. Several factors are responsible for this, including the intrinsic resistance of many gramnegative bacilli, and the role of transferable resistance by which a sensitive pathogen in a mixed flora of gramnegative bacilli may at one step acquire a high degree of resistance to several useful antibiotics. The practice of combined therapy with two or more unrelated antimicrobial agents, which has proved so valuable in preventing the emergence of resistant mutants of tubercle bacilli, obviously has no place in the control of resistance due to R factors; but methods aimed against the selection of resistant variants, in particular limitation of use and careful selection of antibiotics, are more likely to succeed. 1,2 The emergence several years ago in a burns unit of Pseudomonas aeruginosa highly resistant to carbenicillin was shown to be due to transfer of an R factor probably acquired in the first instance from a gram-negative bacillus belonging to the unrelated group of EnteroThis R factor transferred linked bacteriaceae.3-5 resistance to five antibiotics (tetracycline, kanamycin, carbenicillin, ampicillin, and cephaloridine), the full range of which was apparent when the recipient was a strain of Escherichia coli sensitive to all five of these antibiotics, though not when the recipient was P. aruginosa, against which carbenicillin is usually the only effective antibiotic of this set.6 An excepPrice, D. J., Sleigh, J. D. Lancet, 1970, ii, 1213. Bulger, R. J., Sherris, J. C. Ann. intern. Med. 1968, 69, 1099. Lowbury, E. J. L., Kidson, A., Lilly, H. A., Ayliffe, G. A. J., Jones, R. J. Lancet, 1969, ii, 448. 4. Sykes, R. B., Richmond, M. H. Nature, 1970, 226, 952. 5. Fullbrook, P. D., Elson, J. W., Slocombe, B. ibid. p. 1055. 6. Roe, E., Jones, R. J., Lowbury, E. J. L. Lancet, 1971, i, 149.
1. 2. 3.
962
tionally large proportion of kanamycin-resistant strains of Proteus mirabilis, Klebsiella aerogenes, and E. coli found in the burns unit and associated with the 7 presence of this R factor. When the use of carbenicillin in the unit was stopped, carbenicillin-resistant P. aeruginosa disappeared, but it rapidly re-emerged in the infected burns of a patient treated with carbenicillin, probably because of the transfer of an R factor from another organism in the mixed flora of the burn. 8 The ban on carbenicillin had-not surprisingly-been ineffective in eliminating R-factorcarrying strains of other bacteria having a wider range of antibiotic sensitivity. In this issue (p. 941) Dr. Lowbury and his colleagues describe the elimination of bacteria carrying the R factor from the same burns unit. A survey made while such strains were still common in burns showed their virtual absence from the hospital environment, and no human carriers of these strains were found among members of the staff. This information and the rarity of a similar R factor in other hospitals 8 suggested that the task of clearing the unit of the R factor was not insuperable, and might perhaps be achieved by regulation of the use of antibiotics. The ban on antibiotics, previously limited to carbenicillin, was therefore extended to cover all five of the antibiotics against which the R factor was known to determine resistance; gram-negative bacilli, including P. aruginosa showing characteristics of the R factor, disappeared and have remained absent for three months. At the same time the frequency of kanamycinresistant P. mirabilis, K. aerogenes, and E. coli has fallen to levels commonly found in hospitals. Though it would be premature to claim a decisive victory over the R factor, this investigation illustrates the potential usefulness of an antibiotic policy based on current resistance patterns. By such means the doom envisaged in an earlier editorial9 may well be were
averted.
FROM RAT TO MAN
THE Association for Advancement of Behavior
Therapy lately had its sixth annual meeting in New York to take stock of the new discipline. A lot has happened since Skinner’s black box and Miller’s white rat first suggested that man’s behaviour might be shaped or conditioned like that of animals. As with many new movements, behaviour therapy began with an aggressive assault on an established treatment. The new treatment’s good grounding in learning theory, close adherence to scientific method, and quick results in previously untreatable patients assured its rapid growth. In America, particularly, behaviour therapy opened the clinic to psychologists as well as psychiatrists, but, as this meeting showed, the applications have spread into almost every corner of behavioural science, including schools, prisons, State hospitals, clinics, and finally the home. Every developing science spawns its own jargon, so that the neophyte 7. Roe, E.,
Lowbury, E. J. L. J. clin. Path. 1972, 25, 176.
Ayliffe, G. A. J., Lowbury, E. J. L., Roe, E. Nature New Biol. 1972, 235, 141. 9. Lancet, 1971, i, 173. 8.
soon
learns
cope with contingencies, shaping, extinction, response cost, and the like.
to
reinforcement,
Proliferation of approaches is also a feature of developing disciplines. The science of behaviour therapy now embraces techniques that include aversion, desensitisation, flooding, covert conditioning, token economics,
contingency contracting, response prevention, autogenic training, biofeedback procedures, and a host of less defined interventions in a variety of marital, sexual, and social situations. This multiplicity of techniques only reflects the fact that, like psychoanalysis, behaviour modification is founded on theories that can be applied to all forms of behaviour. Despite this global utility one speaker expressed concern that therapists had not addressed themselves to real clinical
problems and that the last four issues of their journal had contributed mainly to the treatment of snake phobia on college campuses. This unkind stricture was incompatible with a wide variety of applications discussed at the meeting, which ranged from teaching patients to abort their own headaches control their own heart-rates, to the use of a computer to correct the family communication patterns of a bickering couple. Such a variety of approaches raised some concern over competing schools. A discernible rift exists between those who have adopted an eclectic approach to anything that works, and the hard-line experimentalists who deplore an absence of scientific rigor in some of these attempts to help. The inevitable discovery that humans are not white rats, and that not all contingencies are under control, has certainly resulted in recognition that individual motivation and social factors operate on the patient. Even Wolpe conceded that agoraphobia was often untreatable until marital discord was resolved. Confronted with these less tangible events some behaviourists have tended to abandon measurement, and already a school of " humanistic " behaviourism has appeared. Another effect has been to extend therapeutic efforts beyond the immediate behaviour. One expert finds that six sessions no longer suffice and has abandoned such " patchwork " in favour of weekly sessions lasting a year, during which he attempts to shift his wealthy patients’ value system from extrinsic goals (money, ambition) to intrinsic ideals (" being happy "). Some of these philosophical excursions are uncomfortably reminiscent of psychoanalytic dogma. Apart from its own growing pains, behaviour therapy has had to contend with the social backlash of a public concerned about being controlled. Just as " Clockwork Orange " voiced these fears, so a school bulletin lately carried an article entitled " Behavior Modification In The Classroom-The Road To Hell Paved With Good Intentions ?". At the meeting itself, there were angry recriminations by the gay liberation movement, who felt that teaching a male homosexual to respond to female imagery with electric shocks was more a sadistic social act than a concerned attempt to assist the individual. Despite all these difficulties, inherent in an expanding discipline, the meeting conveyed an impression of a force that will become an increasingly strong influence in psychiatry and society as a whole. or
bradykinin in the gut wall, and 5-H.T., gastrin, cholecystokinin, secretin, and angiotensin in the blood. High blood-levels of 5-H.T. in the carcinoid syndrome probably cause the diarrhoea of that disease, and cholecystokinin can reproduce, in patients with irritable bowel, the contractions and pain of the syndrome 1; but for the other substances the evidence that they are involved in disorderly gut movement is scanty. And if they are, it might be indirectly-for example, by affecting smooth muscle in blood-vessels rather than in gut wall, or by affecting ganglionic relays. Disorderly motility at any level means one of four things: increased propulsion (diarrhoea); diminished propulsion (achalasia of the cardia, delayed gastric emptying, ileus, constipation); retropulsion (vomiting and duodenogastric reflux); or excessive contraction (colic, diverticular disease, irritable-bowel syndrome). Of all of these the irritable-bowel syndrome is probably the most troublesome diagnosis to make, since it can only be reached by lengthy and comprehensive exclusion of structural gut troubles. The pain is usually in the left iliac fossa, but it may be anywhere in the belly, and there is usually increased frequency of bowel opening and painful postprandial distension. Like other recurrent abdominal complaints it is often associated with psychiatric troubles. A source of bulk in the diet and an anticholinergic drug or mebeverine are helpful. In support of Burkitt’s dietary-fibre hypothesis, Hodgson2 has found high intracolonic
stance
P and
pressures in rabbits fed on a low-residue diet. Such pressures are seen in irritable-bowel syndrome and may eventually lead to diverticular disease. Amitrip-
tyline and other tricyclic antidepressants possibly have a direct action on the bowel. There is need for a specific test for the irritable-bowel syndrome; it would save much time and money. The mouthto-anus transit-time and the 24-hour faecal weight are easily measured but are not very helpful. Only specialised centres can mount tests such as gastricemptying time, small-intestinal transit, colonic propulsive mass movements, or non-propulsive
segmentation. A great deal has been learned from intraluminal Under experimental conpressure measurements. ditions, gut contractions have been recorded so fierce that intraluminal pressures exceeded arterial bloodpressure. Yet they were completely painless. This suggests that the painful colic in smooth-muscle spasm is not due to gut-wall ischoemia. Diarrhoea, of course, is usually a symptom of structural disease of the gut, but in a proportion of patients it is explicable only as a disorder of function. Most treatments are symptomatic-little is known about how they act. Paradoxically, rational treatment is available for the rare patient with carcinoid syndrome, where diarrhoea due to excess circulating 5-H.T. is often controllable by the
specific antagonist methysergide. Constipation is the other main disorder of colonic motility, but here, too, simple questions remain unanswered. What is the consistency of a normal human stool ? In this should we more resemble cows or rabbits ? What, indeed, is constipation ? 1. 2.
Harvey, R. F., Read, A. E. Gut, 13, 837 (abstr.). Hodgson, J. ibid. p. 838 (abstr.).
Regular laxative-taking increases with age, from about 10% in the 20-30 year age-group, to over 50% in those over 60. A moral tone is often wrapped up in laxative habituation, users speaking about a good clearout or a brisk purge, as though the artificial production of diarrhoea had some innate puritanical virtue. Some patients are started on the laxative habit in hospital, and the resultant loss of normal bowelopening rhythm can be a serious matter for disabled people, who become afraid to leave home if they are subject to urgent calls to stool. Of the various classes of laxatives most, such as bulk additives, osmotic expanders, and stool lubricants, are harmless. But the anthroquinone group, which includes the popular senna, are strong cell poisons when given parenterally. They are effective in small oral doses, but there is good reason to believe that they damage the gut wall if taken habitually. In the laxative-abuse syndrome, ever-increasing amounts are taken by the addict, whose colon is eventually converted into a passive tube incapable of peristalsis. The only treatment may be colectomy. Yet there is very little supervision of laxative-prescribing in hospitals. Nurses, who them be much more should aware of most, prescribe their serious side-effects and addictive properties.
R FACTORS AND ANTIBIOTIC USAGE THE problems of controlling resistant gram-nega-
tive infections in hospital have proved even more complex and elusive than the control of resistant
staphylococci. Several factors are responsible for this, including the intrinsic resistance of many gramnegative bacilli, and the role of transferable resistance by which a sensitive pathogen in a mixed flora of gramnegative bacilli may at one step acquire a high degree of resistance to several useful antibiotics. The practice of combined therapy with two or more unrelated antimicrobial agents, which has proved so valuable in preventing the emergence of resistant mutants of tubercle bacilli, obviously has no place in the control of resistance due to R factors; but methods aimed against the selection of resistant variants, in particular limitation of use and careful selection of antibiotics, are more likely to succeed. 1,2 The emergence several years ago in a burns unit of Pseudomonas aeruginosa highly resistant to carbenicillin was shown to be due to transfer of an R factor probably acquired in the first instance from a gram-negative bacillus belonging to the unrelated group of EnteroThis R factor transferred linked bacteriaceae.3-5 resistance to five antibiotics (tetracycline, kanamycin, carbenicillin, ampicillin, and cephaloridine), the full range of which was apparent when the recipient was a strain of Escherichia coli sensitive to all five of these antibiotics, though not when the recipient was P. aruginosa, against which carbenicillin is usually the only effective antibiotic of this set.6 An excepPrice, D. J., Sleigh, J. D. Lancet, 1970, ii, 1213. Bulger, R. J., Sherris, J. C. Ann. intern. Med. 1968, 69, 1099. Lowbury, E. J. L., Kidson, A., Lilly, H. A., Ayliffe, G. A. J., Jones, R. J. Lancet, 1969, ii, 448. 4. Sykes, R. B., Richmond, M. H. Nature, 1970, 226, 952. 5. Fullbrook, P. D., Elson, J. W., Slocombe, B. ibid. p. 1055. 6. Roe, E., Jones, R. J., Lowbury, E. J. L. Lancet, 1971, i, 149.
1. 2. 3.
962
tionally large proportion of kanamycin-resistant strains of Proteus mirabilis, Klebsiella aerogenes, and E. coli found in the burns unit and associated with the 7 presence of this R factor. When the use of carbenicillin in the unit was stopped, carbenicillin-resistant P. aeruginosa disappeared, but it rapidly re-emerged in the infected burns of a patient treated with carbenicillin, probably because of the transfer of an R factor from another organism in the mixed flora of the burn. 8 The ban on carbenicillin had-not surprisingly-been ineffective in eliminating R-factorcarrying strains of other bacteria having a wider range of antibiotic sensitivity. In this issue (p. 941) Dr. Lowbury and his colleagues describe the elimination of bacteria carrying the R factor from the same burns unit. A survey made while such strains were still common in burns showed their virtual absence from the hospital environment, and no human carriers of these strains were found among members of the staff. This information and the rarity of a similar R factor in other hospitals 8 suggested that the task of clearing the unit of the R factor was not insuperable, and might perhaps be achieved by regulation of the use of antibiotics. The ban on antibiotics, previously limited to carbenicillin, was therefore extended to cover all five of the antibiotics against which the R factor was known to determine resistance; gram-negative bacilli, including P. aruginosa showing characteristics of the R factor, disappeared and have remained absent for three months. At the same time the frequency of kanamycinresistant P. mirabilis, K. aerogenes, and E. coli has fallen to levels commonly found in hospitals. Though it would be premature to claim a decisive victory over the R factor, this investigation illustrates the potential usefulness of an antibiotic policy based on current resistance patterns. By such means the doom envisaged in an earlier editorial9 may well be were
averted.
FROM RAT TO MAN
THE Association for Advancement of Behavior
Therapy lately had its sixth annual meeting in New York to take stock of the new discipline. A lot has happened since Skinner’s black box and Miller’s white rat first suggested that man’s behaviour might be shaped or conditioned like that of animals. As with many new movements, behaviour therapy began with an aggressive assault on an established treatment. The new treatment’s good grounding in learning theory, close adherence to scientific method, and quick results in previously untreatable patients assured its rapid growth. In America, particularly, behaviour therapy opened the clinic to psychologists as well as psychiatrists, but, as this meeting showed, the applications have spread into almost every corner of behavioural science, including schools, prisons, State hospitals, clinics, and finally the home. Every developing science spawns its own jargon, so that the neophyte 7. Roe, E.,
Lowbury, E. J. L. J. clin. Path. 1972, 25, 176.
Ayliffe, G. A. J., Lowbury, E. J. L., Roe, E. Nature New Biol. 1972, 235, 141. 9. Lancet, 1971, i, 173. 8.
soon
learns
cope with contingencies, shaping, extinction, response cost, and the like.
to
reinforcement,
Proliferation of approaches is also a feature of developing disciplines. The science of behaviour therapy now embraces techniques that include aversion, desensitisation, flooding, covert conditioning, token economics,
contingency contracting, response prevention, autogenic training, biofeedback procedures, and a host of less defined interventions in a variety of marital, sexual, and social situations. This multiplicity of techniques only reflects the fact that, like psychoanalysis, behaviour modification is founded on theories that can be applied to all forms of behaviour. Despite this global utility one speaker expressed concern that therapists had not addressed themselves to real clinical
problems and that the last four issues of their journal had contributed mainly to the treatment of snake phobia on college campuses. This unkind stricture was incompatible with a wide variety of applications discussed at the meeting, which ranged from teaching patients to abort their own headaches control their own heart-rates, to the use of a computer to correct the family communication patterns of a bickering couple. Such a variety of approaches raised some concern over competing schools. A discernible rift exists between those who have adopted an eclectic approach to anything that works, and the hard-line experimentalists who deplore an absence of scientific rigor in some of these attempts to help. The inevitable discovery that humans are not white rats, and that not all contingencies are under control, has certainly resulted in recognition that individual motivation and social factors operate on the patient. Even Wolpe conceded that agoraphobia was often untreatable until marital discord was resolved. Confronted with these less tangible events some behaviourists have tended to abandon measurement, and already a school of " humanistic " behaviourism has appeared. Another effect has been to extend therapeutic efforts beyond the immediate behaviour. One expert finds that six sessions no longer suffice and has abandoned such " patchwork " in favour of weekly sessions lasting a year, during which he attempts to shift his wealthy patients’ value system from extrinsic goals (money, ambition) to intrinsic ideals (" being happy "). Some of these philosophical excursions are uncomfortably reminiscent of psychoanalytic dogma. Apart from its own growing pains, behaviour therapy has had to contend with the social backlash of a public concerned about being controlled. Just as " Clockwork Orange " voiced these fears, so a school bulletin lately carried an article entitled " Behavior Modification In The Classroom-The Road To Hell Paved With Good Intentions ?". At the meeting itself, there were angry recriminations by the gay liberation movement, who felt that teaching a male homosexual to respond to female imagery with electric shocks was more a sadistic social act than a concerned attempt to assist the individual. Despite all these difficulties, inherent in an expanding discipline, the meeting conveyed an impression of a force that will become an increasingly strong influence in psychiatry and society as a whole. or