1265 remain largely unsolved for cholecystokinin where there is little or no international agreement on circulating concentrations. There is considerable interaction among the gut hormones. Thus, for example, control of pancreatic function involves several hormones and gastric acid output is the result of a delicate balance between agonists and antagonists. It is therefore important to try to gain an overall picture of the hormonal milieu by the measurement of several hormones simultaneously. Only then can we understand the subtle disturbances in balance which may result in disease. Gut-hormone responses form a rapidly expanding new area of investigation, one that must be pursued. Department of Medicine,
Royal Postgraduate Medical School, Hammersmith Hospital, London W12 0HS
S. R. BLOOM H. S. BESTERMAN
CIMETIDINE AND RENAL-ALLOGRAFT
REJECTION
SIR,-Reports published in The Lancet have warned that histamine Hz-receptor antagonist may be associated with increased delayed hypersensitivity (March 25, p. 624) and untoward effects on kidney transplants. Dr Primack (April 15, p. 824) reported two cases of unusual kidney allograft rejections in patients on short-term treatment with cimetidine. On the other hand Dr Doherty and Dr McGeown (May 13, p. 1048) found no evidence of increased susceptibility to rejection in transplant patients, and Mr Rudge and his colleagues (May
after the first month. No gastric complications were encountered in group B. Cimeudine had no effect on rejection episodes or graft function (see table) even though incompatible grafts and untransfused patients were more frequent in the cimetidinetreated group.
given
Service de
Nephrologie, Hôpital P. Brousse,
94800
B. CHARPENTIER D. FRIES
Villejuif, France
ORLOV
Sm,—You criticise (May 27, p. 1139) the U.S. National Academy of Sciences for cancelling its trip to Moscow, on the grounds that personal contacts can only suffer from such action. But do you seriously believe that Russian scientists do not know what is going on in their country, and that if they did they could in some way influence their Government’s policies in the slightest respect? I am not aware that, brave though he is, Professor Sakharov has met with any success. And how many others would be prepared to put their jobs and safety at risk? No doubt people who sup with the devil like to kid themselves and others that they are really fighting the good fight. But they are not. For the Soviet Government will simply interpret their continued visits as business as usual. Which is why, with respect, your criticism is understandable but wrong. 50 Hampstead London NW11
Way,
LIONEL BLUMENTHAL
27, p. 1134) agreed. At this centre 63 patients were given cadaveric allografts between January, 1974, and September, 1977, and 46 patients (group A) were included in this study. The other 17 lost their allograft in the first 3 months for non-immunological reasons
REJECTION
*Received at least 5 units of whole blood.
t2 or more matches. :j:Serum-creatmine 2 mg/dl. 14 patients were transplanted between October, 1977, and February, 1978, and 12 of these patients formed group B; the other 2 had lost their allograft for non-immunological reasons. All patients were given azathioprine 2-5 mg/kg and prednisone 2 mg/kg/day tapered down to 40 mg/day and then 20 mg/day. Rejection episodes were treated with increased doses of prednisone (3 mg/kg for 3 days) and anti-lymphocyte globulins (Behring) for 10 days. To avoid gastroduodenal bleeding, all patients in group A received routinely an anticholinergic drug (diphemanil-methylsulphate 200 mg/day) and antacid (aluminium gel). 1 fatal case of gastroduodenal bleeding and 3 cases of gastroduodenal ulcerations proven by endoscopy were encountered in group A, I a frequency similar to that reported by others.’ In group B the 12 patients received cimetidine 800 mg/day routinely after the postoperative day for a month, together with antacid. Diphemanil methylsulphate (200 mg/day) was 1. Moore, T C., Hume, D. M. Ann. Surg 1969, 170, 1.
SiR,—Dr Sillence and Dr Rimoin (May 13, p. 1041) have a useful classification of osteogenesis imperfecta (0.1.) into five clinical genetic types. Allocation to one or other group depends upon genetic pattern and clinical features such as deafness, degree of bone deformity, scleral colour, and survival in infancy. Since these differences are not biochemical it is surprising that they should criticise as premature Dr Levin and colleagues’ (Feb. 11, p. 332) division of o.i. type i into those with and without dentinogenesis imperfecta because of the absence of definitive biochemical changes. Probably both groups are correct and clinical genetic and biochemical differences occur within these five groups, as Sillence and Rimoin hint. The biochemistry of 0.1. is well advanced and supports this possibility. Abnormalities of collagen chemistry have been conclusively shown in 0.1. type n (lethal broad-boned type) and strongly suggested in 0.1. type I. Pentinnen et al.’ and Muller et al. independently showed that cultured skin fibroblasts from 0.1. type n produce much reduced amounts of type i collagen (although the clinical details of Muller’s case were sparse). Type I collagen is the only type occurring in bone. If 0.1. type u is autosomal recessive as Sillence and Rimoin suggest identification of carrier parents should now be possible. Perhaps, however, this type is itself heterogeneous; Trelstad et al.,3 examining tissues from a lethal variety of 0.1., found no significant differences in skin type i/m ratios. Furthermore the pattern of collagens produced by cultured fibroblasts differed from that of Pentinnen et al.’ and Muller et al. as no apparent increase of type m collagen could be seen. Trelstad et al.3 did show that lysyl hydroxylation was increased in collagens from their patient. Sykes et awl.’ have shown that skin from various
proposed
(wound infections, urinary fistulas). EFFECT OF CIMETIDINE UPON ALLOGRAFT
HETEROGENEITY OF OSTEOGENESIS IMPERFECTA
Pentinnen, R. P., Lichtenstein, J. R., Marlin, G. R., McKusick, V. A. Proc natn. Acad. Sci. U.S.A. 1975, 75, 586. 2. Muller, P. K., Lemmen, C., Gay, S., Meigel, W. N. Eur. J. Biochem. 1975, 59, 97. 3. Trelstad, R. L., Rubin, D., Gross, J. Lab. Invest. 1977, 36, 501. 4. Sykes, B., Francis, M. J. O., Smith, R. New Engl J. Med. 1977, 296, 1200. 1.
1266 ii contain reduced ratios of i/m collagen with controls and suggest heterogeneity varying with the amount of reduction. Recent advances in collagen chemistry (reviewed in your editorial of May 20) should now allow other molecular defects to be identified. Studies of biopsy and necropsy material (frozen and unfixed) together with cultured fibroblasts are essential to this. Clinicians caring for 0.1. patients now hold the key to a more complete understanding of this disease.
AGGLUTININS TO CAUSATIVE ORGANISM OF CONTAGIOUS EQUINE METRITIS 1977 IN HUMAN SERUM
types of 0.1. typeand
compared
Division of Cell Pathology, Clinical Research Centre, Harrow, Middlesex HA1 3UJ
F. M. POPE A. C. NICHOLLS
SEQUELÆ OF COVERT BACTERIURIA IN SCHOOLGIRLS
SIR,-The Cardiff/Oxford Bacteriuria Study Group agrees with Professor Arneil (May 20, p. 1093) that the contrast between our treated and control groups was not as sharp as we would have wished. This matter was fully discussed in the paper, and
the difficulty the results were also anathe duration of bacteriuria. We decided treatment because many girls would have received antimicrobials unnecessarily, because there is a sizeable spontaneous cure-rate, and because a large proportion of the girls do respond to the initial short course(s) of treatment.’I Even if continuous treatment had been given from the start, the contrast between treated and control groups might not have been greater. Daschner and MargetZ showed that only a third of a group of 105 children with recurrent symptomatic urinary-tract infection who were put on continuous treatment took their medication regularly. This lack of compliance was mainly due to parental forgetfulness and negligence. It seems unlikely that the parents of symptomless girls, who would be to overcome
lysed according to against continuous
less motivated, would do better. Our conclusion that screening schoolgirls for bacteriuria cannot be recommended at present was based on the observation that new kidney damage in previously normal kidneys was not seen over the 4-year follow-up. It is possible, but not proven, that progression of pre-existing kidney damage can be slowed or prevented by treatment, but we do not as yet know what factors produce progression of kidney damage. They may include rise of blood-pressure, the effects of back pressure from associated vesico-ureteric reflux, the development of glomerular lesions, and the possible effect of continuing or recurrent infection. We are continuing the follow-up of our schoolgirls into adult life in an attempt to establish the relative importance of these factors. Our results and those obtained in Dundee3 and Goteborg4 show that infection does not appear to be an important factor in the progression of kidney damage. Until these problems have been solved we do not share Arneil’s enthusiasm for bacteriuria screening in schoolgirls other than for research purposes. The criteria of a successful screening technique were laid down by Wilson and Jungner5 and have not so far been satisfied for bacteriuria screening of schoolgirls. Arneil objects to the use of the term "covert bacteriuria". This refers to significant bacteriuria detected during screening of apparently healthy populations. Had we used "latent urinarytract infection", as he advises, we would have accorded the status of a disease to an abnormal laboratory finding and prejudged the outcome of our study. K.R.U.F. Institute of Renal
Royal Infirmary, Cardiff CF2 1SZ
Disease, A. W. ASSCHER
1. Verrier-Jones, E. R. Kidney Int. 1975, 8, Suppl. 4, 85. 2. Daschner, F., Marget, W. Acta pœdiat. scand. 1975, 64, 105. 3. Savage, D. C. L., and others Lancet, 1975, i, 358. 4. Lindberg, V., and others J. Pediat. 1978, 92, 194. 5. Wilson, J. M. G., Jungner, G. Principles and Practice of Screening for Disease. W.H.O., Geneva, 1968.
SIR,-Dr Tayldr and Mr Rosenthal (May 13,
p. 1038) intriguing finding, that sera from patients attending genitomedical clinic showed low titre agglutination of the Gram-negative rod-shaped bacterium of contagious equine metritis (C.E.M.) more frequently than did sera from healthy
report
an
adult persons. The taxonomic position of this apparently new animal pathogen is still uncertain. We have some preliminary evidence, based on agglutinin-absorption studies, of partial crossreactions between the oxidase-positive c.E.M. bacterium and Moraxella liquefaciens and also strains of Mima polymorpha (Acinetobacter calcoaceticus); we have not yet examined serological relationships with Moraxella urethralis by this tech-
nique. Gram-negative, oxidase-positive, rod-shaped bacteria are well known occasional isolates from gonorrhoea-like infections in man.I,2 They can be looked for only from patients whose condition obliges them to attend a clinic; the incidence of these bacteria in low-grade, transient genital inflammations (which are probably frequent unreported occurrences in the venerealclinic recidivist) cannot be estimated. However, such nongonococcal infections, whether clinical or subclinical, could well lead to the formation of antibodies non-reacting at low agent, and we suggest that this is a more acceptable interpretation of the findings of Taylor and Rosenthal than their alternative, which postulates some kind of direct cross-infection from horse to man. titre with the
c.E.M.
Department of Microbiology, University of Surrey, Guildford, Surrey GU2 5XH
J. E. SMITH C. R. YOUNG
INDICATIONS FOR ADENOTONSILLECTOMY
SIR,-In response to your editorial of April 1 (p. 700) I would point out that objective criteria for chronic tonsillitis in adults were identified in a controlled study reported to the American Academy of Ophthalmology and Otolaryngology in 1977.3 Recent data statistically identify a form of chronic bacterial tonsillitis in patients aged 18-35 who have more than seven episodes of sore throat and malaise per year, palpable jugular-digastric nodes, smaller than average tonsils, and relative absence of visible tonsil crypts. The presence of chronic infection is established by quantitative bacteriological methods, comparing tonsils of patients with symptoms with tonsils of controls who have undergone tonsillectomy for a variety of unrelated reasons including relief of airway obstruction and removal of second brachial cleft cysts. Mean counts of bacteria/g tonsil tissue were 2-1x 106 in 20 patients with symptoms and 7-8 x 103 in 9 controls (P
Royal Postgraduate Medical School, Hammersmith Hospital, London W12 0HS
S. R. BLOOM H. S. BESTERMAN
CIMETIDINE AND RENAL-ALLOGRAFT
REJECTION
SIR,-Reports published in The Lancet have warned that histamine Hz-receptor antagonist may be associated with increased delayed hypersensitivity (March 25, p. 624) and untoward effects on kidney transplants. Dr Primack (April 15, p. 824) reported two cases of unusual kidney allograft rejections in patients on short-term treatment with cimetidine. On the other hand Dr Doherty and Dr McGeown (May 13, p. 1048) found no evidence of increased susceptibility to rejection in transplant patients, and Mr Rudge and his colleagues (May
after the first month. No gastric complications were encountered in group B. Cimeudine had no effect on rejection episodes or graft function (see table) even though incompatible grafts and untransfused patients were more frequent in the cimetidinetreated group.
given
Service de
Nephrologie, Hôpital P. Brousse,
94800
B. CHARPENTIER D. FRIES
Villejuif, France
ORLOV
Sm,—You criticise (May 27, p. 1139) the U.S. National Academy of Sciences for cancelling its trip to Moscow, on the grounds that personal contacts can only suffer from such action. But do you seriously believe that Russian scientists do not know what is going on in their country, and that if they did they could in some way influence their Government’s policies in the slightest respect? I am not aware that, brave though he is, Professor Sakharov has met with any success. And how many others would be prepared to put their jobs and safety at risk? No doubt people who sup with the devil like to kid themselves and others that they are really fighting the good fight. But they are not. For the Soviet Government will simply interpret their continued visits as business as usual. Which is why, with respect, your criticism is understandable but wrong. 50 Hampstead London NW11
Way,
LIONEL BLUMENTHAL
27, p. 1134) agreed. At this centre 63 patients were given cadaveric allografts between January, 1974, and September, 1977, and 46 patients (group A) were included in this study. The other 17 lost their allograft in the first 3 months for non-immunological reasons
REJECTION
*Received at least 5 units of whole blood.
t2 or more matches. :j:Serum-creatmine 2 mg/dl. 14 patients were transplanted between October, 1977, and February, 1978, and 12 of these patients formed group B; the other 2 had lost their allograft for non-immunological reasons. All patients were given azathioprine 2-5 mg/kg and prednisone 2 mg/kg/day tapered down to 40 mg/day and then 20 mg/day. Rejection episodes were treated with increased doses of prednisone (3 mg/kg for 3 days) and anti-lymphocyte globulins (Behring) for 10 days. To avoid gastroduodenal bleeding, all patients in group A received routinely an anticholinergic drug (diphemanil-methylsulphate 200 mg/day) and antacid (aluminium gel). 1 fatal case of gastroduodenal bleeding and 3 cases of gastroduodenal ulcerations proven by endoscopy were encountered in group A, I a frequency similar to that reported by others.’ In group B the 12 patients received cimetidine 800 mg/day routinely after the postoperative day for a month, together with antacid. Diphemanil methylsulphate (200 mg/day) was 1. Moore, T C., Hume, D. M. Ann. Surg 1969, 170, 1.
SiR,—Dr Sillence and Dr Rimoin (May 13, p. 1041) have a useful classification of osteogenesis imperfecta (0.1.) into five clinical genetic types. Allocation to one or other group depends upon genetic pattern and clinical features such as deafness, degree of bone deformity, scleral colour, and survival in infancy. Since these differences are not biochemical it is surprising that they should criticise as premature Dr Levin and colleagues’ (Feb. 11, p. 332) division of o.i. type i into those with and without dentinogenesis imperfecta because of the absence of definitive biochemical changes. Probably both groups are correct and clinical genetic and biochemical differences occur within these five groups, as Sillence and Rimoin hint. The biochemistry of 0.1. is well advanced and supports this possibility. Abnormalities of collagen chemistry have been conclusively shown in 0.1. type n (lethal broad-boned type) and strongly suggested in 0.1. type I. Pentinnen et al.’ and Muller et al. independently showed that cultured skin fibroblasts from 0.1. type n produce much reduced amounts of type i collagen (although the clinical details of Muller’s case were sparse). Type I collagen is the only type occurring in bone. If 0.1. type u is autosomal recessive as Sillence and Rimoin suggest identification of carrier parents should now be possible. Perhaps, however, this type is itself heterogeneous; Trelstad et al.,3 examining tissues from a lethal variety of 0.1., found no significant differences in skin type i/m ratios. Furthermore the pattern of collagens produced by cultured fibroblasts differed from that of Pentinnen et al.’ and Muller et al. as no apparent increase of type m collagen could be seen. Trelstad et al.3 did show that lysyl hydroxylation was increased in collagens from their patient. Sykes et awl.’ have shown that skin from various
proposed
(wound infections, urinary fistulas). EFFECT OF CIMETIDINE UPON ALLOGRAFT
HETEROGENEITY OF OSTEOGENESIS IMPERFECTA
Pentinnen, R. P., Lichtenstein, J. R., Marlin, G. R., McKusick, V. A. Proc natn. Acad. Sci. U.S.A. 1975, 75, 586. 2. Muller, P. K., Lemmen, C., Gay, S., Meigel, W. N. Eur. J. Biochem. 1975, 59, 97. 3. Trelstad, R. L., Rubin, D., Gross, J. Lab. Invest. 1977, 36, 501. 4. Sykes, B., Francis, M. J. O., Smith, R. New Engl J. Med. 1977, 296, 1200. 1.
1266 ii contain reduced ratios of i/m collagen with controls and suggest heterogeneity varying with the amount of reduction. Recent advances in collagen chemistry (reviewed in your editorial of May 20) should now allow other molecular defects to be identified. Studies of biopsy and necropsy material (frozen and unfixed) together with cultured fibroblasts are essential to this. Clinicians caring for 0.1. patients now hold the key to a more complete understanding of this disease.
AGGLUTININS TO CAUSATIVE ORGANISM OF CONTAGIOUS EQUINE METRITIS 1977 IN HUMAN SERUM
types of 0.1. typeand
compared
Division of Cell Pathology, Clinical Research Centre, Harrow, Middlesex HA1 3UJ
F. M. POPE A. C. NICHOLLS
SEQUELÆ OF COVERT BACTERIURIA IN SCHOOLGIRLS
SIR,-The Cardiff/Oxford Bacteriuria Study Group agrees with Professor Arneil (May 20, p. 1093) that the contrast between our treated and control groups was not as sharp as we would have wished. This matter was fully discussed in the paper, and
the difficulty the results were also anathe duration of bacteriuria. We decided treatment because many girls would have received antimicrobials unnecessarily, because there is a sizeable spontaneous cure-rate, and because a large proportion of the girls do respond to the initial short course(s) of treatment.’I Even if continuous treatment had been given from the start, the contrast between treated and control groups might not have been greater. Daschner and MargetZ showed that only a third of a group of 105 children with recurrent symptomatic urinary-tract infection who were put on continuous treatment took their medication regularly. This lack of compliance was mainly due to parental forgetfulness and negligence. It seems unlikely that the parents of symptomless girls, who would be to overcome
lysed according to against continuous
less motivated, would do better. Our conclusion that screening schoolgirls for bacteriuria cannot be recommended at present was based on the observation that new kidney damage in previously normal kidneys was not seen over the 4-year follow-up. It is possible, but not proven, that progression of pre-existing kidney damage can be slowed or prevented by treatment, but we do not as yet know what factors produce progression of kidney damage. They may include rise of blood-pressure, the effects of back pressure from associated vesico-ureteric reflux, the development of glomerular lesions, and the possible effect of continuing or recurrent infection. We are continuing the follow-up of our schoolgirls into adult life in an attempt to establish the relative importance of these factors. Our results and those obtained in Dundee3 and Goteborg4 show that infection does not appear to be an important factor in the progression of kidney damage. Until these problems have been solved we do not share Arneil’s enthusiasm for bacteriuria screening in schoolgirls other than for research purposes. The criteria of a successful screening technique were laid down by Wilson and Jungner5 and have not so far been satisfied for bacteriuria screening of schoolgirls. Arneil objects to the use of the term "covert bacteriuria". This refers to significant bacteriuria detected during screening of apparently healthy populations. Had we used "latent urinarytract infection", as he advises, we would have accorded the status of a disease to an abnormal laboratory finding and prejudged the outcome of our study. K.R.U.F. Institute of Renal
Royal Infirmary, Cardiff CF2 1SZ
Disease, A. W. ASSCHER
1. Verrier-Jones, E. R. Kidney Int. 1975, 8, Suppl. 4, 85. 2. Daschner, F., Marget, W. Acta pœdiat. scand. 1975, 64, 105. 3. Savage, D. C. L., and others Lancet, 1975, i, 358. 4. Lindberg, V., and others J. Pediat. 1978, 92, 194. 5. Wilson, J. M. G., Jungner, G. Principles and Practice of Screening for Disease. W.H.O., Geneva, 1968.
SIR,-Dr Tayldr and Mr Rosenthal (May 13,
p. 1038) intriguing finding, that sera from patients attending genitomedical clinic showed low titre agglutination of the Gram-negative rod-shaped bacterium of contagious equine metritis (C.E.M.) more frequently than did sera from healthy
report
an
adult persons. The taxonomic position of this apparently new animal pathogen is still uncertain. We have some preliminary evidence, based on agglutinin-absorption studies, of partial crossreactions between the oxidase-positive c.E.M. bacterium and Moraxella liquefaciens and also strains of Mima polymorpha (Acinetobacter calcoaceticus); we have not yet examined serological relationships with Moraxella urethralis by this tech-
nique. Gram-negative, oxidase-positive, rod-shaped bacteria are well known occasional isolates from gonorrhoea-like infections in man.I,2 They can be looked for only from patients whose condition obliges them to attend a clinic; the incidence of these bacteria in low-grade, transient genital inflammations (which are probably frequent unreported occurrences in the venerealclinic recidivist) cannot be estimated. However, such nongonococcal infections, whether clinical or subclinical, could well lead to the formation of antibodies non-reacting at low agent, and we suggest that this is a more acceptable interpretation of the findings of Taylor and Rosenthal than their alternative, which postulates some kind of direct cross-infection from horse to man. titre with the
c.E.M.
Department of Microbiology, University of Surrey, Guildford, Surrey GU2 5XH
J. E. SMITH C. R. YOUNG
INDICATIONS FOR ADENOTONSILLECTOMY
SIR,-In response to your editorial of April 1 (p. 700) I would point out that objective criteria for chronic tonsillitis in adults were identified in a controlled study reported to the American Academy of Ophthalmology and Otolaryngology in 1977.3 Recent data statistically identify a form of chronic bacterial tonsillitis in patients aged 18-35 who have more than seven episodes of sore throat and malaise per year, palpable jugular-digastric nodes, smaller than average tonsils, and relative absence of visible tonsil crypts. The presence of chronic infection is established by quantitative bacteriological methods, comparing tonsils of patients with symptoms with tonsils of controls who have undergone tonsillectomy for a variety of unrelated reasons including relief of airway obstruction and removal of second brachial cleft cysts. Mean counts of bacteria/g tonsil tissue were 2-1x 106 in 20 patients with symptoms and 7-8 x 103 in 9 controls (P
