180 normal ranges.6,7There is, in the living animal, competition between aminoacids that share common transport systems but the effect is only severe when the blood concentration of the inhibitor is above normal.4,5,8 over

Our results in laboratory animals suggest that the entry tryptophan into the brain is likely to be increased in acute hepatic failure partly as a result of the direct action of insulin upon the system which transports it into the brain, and partly because there is a raised level of free tryptophan 9 in the blood in this condition. We therefore support the view of Curzon et a1. that the level of free tryptophan in the plasma is an important factor in determining the entry of this aminoacid into the brain. In acute hepatic failure not only are the concentrations of the branched-chain aminoacids in the blood reduced, but the concentrations of various other aminoacids-e.g. methionine and phenylalanine 10—are increased considerably. Because of these disturbances in the bloodaminoacid pattern, competition 4,5,8 between these and other aminoacids may play some part in cerebral dysfunction by altering the pattern of essential aminoacids which are being supplied to the brain from the blood. P. M. DANIEL Department of Neuropathology, E. R. LOVE Institute of Psychiatry, S. R. MOORHOUSE De Crespigny Park, O. E. PRATT. London SE5 8AF. of

TRANSPOSONS AND ANTIBIOTIC RESISTANCE editorial SIR,—In your (June 28, p. 1411), you comment at length on a review article of mine. 11 The overall impression is sufficiently at variance with what I actually wrote that I suggest that interested readers should refer to the original article. In this article I attempted to examine objectively the possible interpretation of sets of data (the reliability of the actual data was not questioned). I discussed the arguments for and against transfer. Surely such objective analysis is the essence of review articles ? Your editorial contains a very subjective view of antibiotic resistance. The following statements are either incorrect or should have had factual

backing: (1) The use of phage-typing and serotyping as epidemiological tools were not " cast aside ". After giving detailed examples of the instability of phage typing, I wrote " Thus phage typing has severe limitations in identifying specific strains of S. aureus over several years. This shortcoming of phage-typing possibly applies also to Salmonella typhimurium." Where is the evidence for the stability of phage type in this organism ? (2) " His [mine] explanations of observed facts seem less probable than those of the original observers." Since in most instances, a variety of explanations were offered, it is not surprising that some are more likely than others. I stated this clearly. The essential point I was trying to make was that transfer experiments in the laboratory may or may not apply in nature. More data from clinical sources are needed. Your editorial merely restates the traditional opinion; it does not strengthen it. (3) " Lacey suggests that the unnecessary use of antibiotics may, in some cases, actually be beneficial, because R+ bacteria may (by virtue of having to support the plasmid) be less virulent." 6. 7. 8. 9. 10. 11.

Baños, G., Daniel, P. M., Moorhouse, S. R., Pratt, O. E. Proc. R. Soc. B. 1973, 183, 59. Baños, G., Daniel, P. M., Moorhouse, S. R., Pratt, O. E. J. Physiol. 1975, 246, 539. Baños, G., Daniel, P. M., Pratt, O. E. ibid. 1974, 236, 29. Knell, A. J., Davidson, A. R., Williams, R., Kantamaneni, B. D., Curzon, G. Br. med. J. 1974, i, 549. Knell, A. J., Pratt, O. E., Curzon, G., Williams, R. 8th Symposium of Advanced Medicine; p. 156. London, 1972. Lacey, R. W. J. antimicrob. Chemother. 1975, 1, 25.

I did not mean or say anything like that. What I said was: " The overall impression is, therefore, that apart from the rare instance of the plasmids that determine specific ’virulence factors ’, R-factor and plasmid carriage is associated with loss I did not of virulence, although sometimes very slight." advocate the unnecessary use of antibiotics. (4) A worldwide increase in the frequency of chloramphenicol resistance in the typhoid bacillus is attributed by Prof. E. S. Anderson to the indiscriminate use of antibiotics and few would disagree with him. This was not disputed. In fact I said " R-factor carriage amongst dangerous pathogens, such as Salmonella typhi, is of grave significance." My point was that if R-factor transfer did occur at all frequently in nature, it is surprising that it took so long for any R-factor determining chloramphenicol resistance to appear in this organism.

Department of Bacteriology, North Cambridgeshire Hospital, Wisbech.

R. W. LACEY.

SPRUE AGAIN editorial1 you cite epidemiological observations conducted by our unit in Puerto Rico which document a concomitant peak seasonal incidence of both the onset of symptoms of overt tropical sprue and the occurrence of subclinical malabsorption among the general population of this island.Contrary to what is stated in the editorial, we noted a correlation between this seasonal incidence of intestinal disease, contamination of the small bowel by enterotoxigenic coliform bacterial and an increased dietary intake of long-chain unsaturated fatty acids (especially of linoleic acid) associated with qualitative changes in the dietary pattern of this population that occur during the Christmas season. We did not consider rainfall a significant factor. We should also like to point out that, as presented in the editorial, the hypothesised role of dietary lipids does not make sense. The editorial states: " When these fatty acids are displaced from the diet, bacteria may come in and induce and perpetuate the mucosal lesion." What we suggested is quite the opposite-namely, that the presence of increased quantities of long-chain unsaturated fatty acids in the diet may alter the intestinal bacterial ecosystem by virtue of the well-recognised effect of these lipids in suppressing the growth of gram-positive bacteria, which are the principal flora of the small bowel under normal circumstances, so that there is a decreased resistance to overgrowth by alien organisms such as enterotoxigenic coliform bacteria. Whether this indeed happens within the intestinal tract of man is untested, but we have been able to show that such is the case under laboratory conditions when the effect of linoleic acid on Lactobacillus-Klebsiella interrelationships is examined using a continuous culture system.4 Tropical Malabsorption Unit of the Universities of Rochester and FREDERICK A. KLIPSTEIN Puerto Rico, San Juan, Puerto Rico 00935. JOSÉ J. CORCINO.

SIR,-In

an

HUMAN PLACENTAL LACTOGEN AND DIABETIC PREGNANCY

SIR,—There could be an important aside to the study (July 12, p. 54) of human placental lactogen levels in diabetic pregnancy, which shows higher levels than in normal pregnant women. Since I have published evidence5 that lactogen is probably the cause of the physiological inhibition Lancet, 1975, i, 1019. Klipstein, F. A., Corcino, J. J. Am. J. trop. Med. Hyg. 1974, 23, 1189. Klipstein, F. A., Holdeman, L. V., Corcino, J. J., Moore, W. E. C. Ann. intern. Med. 1971, 75, 41. 4. Mickelson, M. J., Klipstein, F. A. Clin. Res. 1975, 23, 308A. 5. Wardle, E. N. Int. Res. Commun. Syst. 1973 (73-12) 15-14-21. 1. 2. 3

181 of fibrinolysis of normal pregnancy, and there is much evidence that many of the vascular complications of diabetes represent a low-grade consumptive coagulopathy, so pregnancy for the diabetic woman could represent a calculated pathological as well as a clinical risk. In the first instance it would be of interest to know whether there is evidence of deterioration in the retinal circulation of pregnant diabetics. Secondly, an attempted correlative study between lactogen levels and fibrinolytic activity in pregnancy has yet to be done.

the test could not be carried out because of postural hypotension. His retinopathy, assessed photographically, did not alter significantly during the 8 weeks of treatment.

We report this

case to

draw attention

Department of Medicine, Hammersmith Hospital, London W12 0HS.

E. N. WARDLE.

NE3 3DE.

BROMOCRIPTINE AND SERUM-GROWTHHORMONE LEVELS IN DIABETES MELLITUS

dopamine-receptor stimulant,! SIR,-Bromocriptine, growth-hormone secretion in some acromegalics.2-4 Since growth-hormone secretion may play a role in the evolution of diabetic retinopathy,ó,6 we tried to suppress growth-hormone secretion with bromocriptine in a male juvenile diabetic with severe proliferative retinopathy. a

suppresses

The patient, a man aged 31, presented in diabetic ketoacidosis the age of 4 years, and he has been treated with insulin ever since. Currently he is well controlled on two injections of soluble and isophane daily and a 180 g. carbohydrate diet. He was referred to this hospital for management of severe proliferative retinopathy. His blood-pressure was 145/60 mm. Hg and he had no postural hypotension. It was decided to start treatment with bromocriptine in February of this year because of deteriorating retinopathy despite extensive treatment with photocoagulation, and to assess growth-hormone levels monthly at rest and during an exercise test consisting of 20 minutes on a bicycle ergometer at 45% of working capacity.7 Bromocriptine was worked up to a dose of 5 mg. thrice daily over a period of a month. The serum-growthhormone levels in this patient before and 4 weeks after the start of the treatment are shown in the accompanying table. For comparison, the levels in four normal males and four insulintreated male juvenile diabetics are shown. Bromocriptine did not suppress the serum-growth-hormone levels at rest or during exercise. Blood-glucose levels were similar during the two tests. The patient felt generally unwell and complained of some nausea and dizziness while on bromocriptine. He also felt slightly faint after the second exercise test, and a month later at

Corrodi, H., Fuxe, K., Hökfelt, T., Lidbrink, P., Ungerstedt, U. J. Pharm. Pharmac. 1973, 25, 409. 2. Liuzzi, A., Chiodini, P. G., Botalla, L., Cremascoli, G., Müller, E. E., Silvestrini, F. J. clin. Endocr. Metab. 1974, 38, 910. 3. Liuzzi, A., Chiodini, P. G., Botalla, L., Silvestrini, F., Müller, E. E. ibid. 1974, 39, 871. 4. Thorner, M. O., Chait, A., Aitken, M., Benker, G., Bloom, S. R., Mortimer, C. H., Sanders, P., Stuart Mason, A., Besser, G. M. Br. med. J. 1975, i, 299. 5. Lundbæk, K. in Blood Vessel Disease in Diabetes Mellitus (edited by K. Lundbæk and H. Keen). Acta diabet. lat. 1971, 8, suppl. 1, 1.

the fact that

renorted.8e

33 Hawthorn

Gardens, Kenton, Newcastle upon Tyne

to

bromocriptine increased growth-hormone secretion’ in a diabetic and that side-effects were significant. Bromocriptine has been found to increase growth-hormone secretion in normal subjects but no side-effects were J. CASSAR R. EDWARDS K. MASHITER EVA M. KOHNER.

HYPOTENSION DURING ANGIOTENSIN BLOCKADE WITH SARALASIN Sirwas interested to read Dr Pettinger and Dr Keeton’s account (June 21, p. 1387) of hypotension during saralasin (sarl-ala8-angiotensin n) infusion in a patient with resistant hypertension on multiple drug therapy. It was not clear why Dr Pettinger and Dr Keeton started their infusion at a rate of 1 {g. per kg. per min. and increased the infusion-rate from 1 to 3 {j!.g. per kg. per min. when the lying blood-pressure was less than 100/70 mm. Hg. They themselves state that similar patients’ blood-pressures were in some instances controlled with an infusionrate of 0-15 (Jt.g. per kg. per min. Whilst I agree with their conclusion that angiotensin-n blockade with saralasin may lead to hypotension in patients on multiple hypotensive drugs, I think this can be avoided by careful adjustment of the infusion-rate, which should be started at a maximum of 0.100 g. per kg. per min., and by measuring the standing

blood-pressure. The standing blood-pressure appears to be a more sensitive index of angiotensin-n dependency in these relatively volume-depleted patients. The other advantage of measuring standing blood-pressure is that, if hypotension occurs on standing, the patient only needs to lie down to restore a reasonable blood-pressure. In 3 of our patients similar to the one that they describethat is, uncontrolled hypertension on multiple hypotensive therapy-standing blood-pressure fell at a lower rate of infusion and to a greater extent than lying blood-pressure. In all 3 patients, the blood-pressure was lowered to less than 160/100 mm. Hg lying at a maximum infusion-rate of 1 g. per kg. per min. This is illustrated by the following case.

A 46-year-old man with severe hypertension, uncontrolled by combination of propranolol, frusemide, hydrallazine, and methyldopa, was infused with saralasin, starting at a rate of 0-100 jj.g. per kg. per min. The standing blood-pressure started to fall at this rate, and fell progressively as the infusion-rate was a

p. 344. 6. 7.

Luft, R., Guillemin, R. Diabetes, 1974, 23, 783. Hansen, A. P. J. clin. Invest. 1970, 49, 1467.

8.

Camanni, F., Massara, F., Belforte, L., Molinatti, G. M. J. clin. Endocr. Metab. 1975, 40, 363.

SERUM-GROWTH-HORMONE LEVELS AT REST AND DURING EXERCISE

Letter: Human placental lactogen and diabetic pregnancy.

180 normal ranges.6,7There is, in the living animal, competition between aminoacids that share common transport systems but the effect is only severe...
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