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.
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.
