INSTABILITY OF PANCREATIC ENDOCRINE CELL POPULATIONS THROUGHOUT LIFE

615 ASCORBIC ACID

SIR,-Your editorial (Feb. 10, p. 308) seems biased. The sentence reads "Vitamin C, contrary to the suggestion of

first

Pauling, does not seem to decrease the incidence of colds or winter illness." This sentence is followed by others about positive effects-reduction in the severity of the symptoms of the common cold and the interaction of ascorbate in various ways with the immune systems. I suggest that you should have started with this discussion, rather than with the negative statement about the incidence of colds. Moreover, that statement may be misleading. Cowan et al.,’ in the first doubleblind study of ascorbic acid in the common cold, reported a 15% decrease in incidence and a 21% decrease in severity. In several other studies (reviewed elsewhere2) the investigators have reported decreases in both incidence and severity; for example, RitzeP reported a 45% decrease in incidence and 29-36% decrease in severity. I have preferred to discuss the integrated morbidity (the number of days of illness per subject) because it is difficult to assess the incidence since a very mild cold, with symptoms on only one day, may or may not be considered to be a cold.2 Your reference to my book2 ("Pauling, L., San Francisco, 1970") is incomplete. Linus Pauling Institute of Science and Medicine, Menlo Park, California 94025, U.S.A.

LINUS PAULING

SIR,-Your editorial on the possible hazards and benefits of ascorbic acid, together with the persistent interest in this subject (e.g., the study in elderly inpatients by Dr Schorah and colleagues in your issue of Feb. 24) might suggest that vitamin C is a potent drug when administered orally. Even in scurvy, where the vitamin is undetectable in plasma or leucocytes, ascorbic acid may still be found in the urine,4 indicating a zero renal threshhold. Even with gram doses of the vitamin less than 30% of the dose is recovered in the urine while there is no permanent change in the plasma level to account for the discrepancy.5 Some endogenous degradation occurs;6 but oxalate concentrations are not usually high enough to account for the difference either. We must conclude that the vitamin has not entered the blood. In support of this is the fact that increasing the single dose from 1 g by steps to 10 g alters neither the peak plasma level (1.4:tO. mg/dl) nor the time taken for plasina changes to occur after dosage, which is about an hour (unpublished). These findings suggest that transport from the gut is saturable, that the loss from the blood is rapid, and that, if single doses are given, the bulk of the dose may pass out with the faeces. Our published5 and unpublished studies suggest that doses of a daily total of 170 mg in four intakes, as with a particularly good diet, maintain the maximum plasma level. That single large doses have any effect other than those the maximum plasma level achieves is only to be explained in terms of the potency of the vitamin, since, as I have explained, the greater part of the single supplement given orally is never presented to the tissues, while it takes a mere one and a half days for urine and plasma levels to revert to previous values irrespective of the size of an oral dose.s Future research may have to proceed, tentatively it appears, by intravenous injection, which will still mean a reversion within one and a half days, or more potently, by avoiding the 1. Cowan, D. W., Diehl, H. S., Baker, A. B. J. Am. med. Ass. 1942, 120, 1268. 2. Pauling, L. Vitamin C and the Common Cold. W. H. Freeman, San Francisco, 1970. 3. Ritzel, G.Helv. med.Acta, 1961, 28, 63. 4. Vilter, R. W. in The Vitamins (edited by W. H. Sebrell, Jr and R. S. Harris); p. 501.New York. 1967. 5. Harris, A. B., Pillay, M., Moor, A . Chem.-biol. Interact. 1976, 14, 371. 6 Hellman, L. Burns, J. J. J. biol. Chem. 1958, 230, 923.

low renal threshold and rapid elimination from ing the vitamin intramuscularly. 16 Tait House, Ward Road, London N19

blood, and giv-

ANTHONY HARRIS

CHLORPROMAZINE AND FLUID-LOSS IN CHOLERA p.

SiR,—The article by Dr Rabbani and colleagues (Feb. 24, 410) is most interesting, but there may be properties of

chlorpromazine other than inhibition of toxin-stimulated adenyl-cyclase activity that could account for the changes reported. We have for nearly two decades used chlorpromazine to prepostoperative ileus in abdominal cases. We used it at first impression that the more anxious patients had been helped to move about and behave normally if given this drug, and that they would thereby have less tendency to a variety of postoperative complications, but we noticed that the improvevent

under the

disproportionate to this effect alone and then began it on patients of all types. The effect of chlorpromazine on the bowel appears to be similar to that of morphia. Peristalsis becomes more balanced and there is less tendency to dilatation. Peristalsis also does not seem to have the intermittent form, which so often appears, causing a localised ileus and tympanism. The effect is so pronounced that we now regularly use the drug in patients showing signs of postoperative tympanism. Some of the changes observed by Rabbini et al. might well be explained by this effect on bowel tone and mobility.

ment was

to use

General

Hospital, Birmingham B4 6NH

GEORGE T. WATTS

INSTABILITY OF PANCREATIC ENDOCRINE CELL POPULATIONS THROUGHOUT LIFE

SIR,-We have recently reported in these columns that pancreatic polypeptide (PP) containing cells are not equally distributed in all regions of the human pancreas. They are scarce or absent in the body and tail of the organ but always numerous in lobules of the posterior part of the pancreatic head.’ Such observations prompted us to assess this non-homogeneous population with respect to the three other types of islet endocrine cell, and we report here data on all four types in PP-rich and PP-poor lobules of the normal human pancreas in infancy and adulthood. Islet-cell populations were quantitatively assessed by immunofluorescence in light microscopy using specific antisera. Four infant (from 0 to 6 months) and three adult (29, 66, and 80 years) necropsy pancreases were studied, and the following are the average percentages of endocrine cells found:

These data confirm the non-homogeneous distribution of PP-cells, and point to a striking instability of the endocrine-cell populations throughout life; somatostatin-containing cells are particularly affected in this respect since they are nearly 8 times more numerous in infants than in adults in all regions of the pancreas. 1.

Orci, L., Malaisse-Lagae, F., Baetens, D., Perrelet, A. Lancet, 1978, ii, 1200.

616 We thank Dr P. H. Wright, Dr R. H. Unger, Dr R. E. Chance, Dr R. A. Donald, and Dr S. Ito for supplying antibodies; Dr J. Cox and his from the department of pathology, Hopital Cantonal, Geneva, for their help; and 1. Fuglister, A. M. Lucini, and D. Mottier for technical assistance. These studies were supported in part by N.I.H. Contract NOI-AM-7-2213 and the Swiss National Science Foundation, grant no. 3.120.77.

colleagues

Institute of Histology and Embryology, University of Geneva Medical School, 1211 Geneva 4, Switzerland

LELIO ORCI YOLANDE STEFAN FRANCINE MALAISSE-LAGAE ALAIN PERRELET

COPPER LEVELS AFTER ORAL ZINC

influence of oral zinc sulphate on copper metabolism in a patient with Wilson’s disease. We found that plasma-zinc levels reached a peak of 28 mol/1 during 12-weeks’ oral zinc intake of 2.07 mmol (135 mg) in seven healthy adults.2 In a second study, another group of seven healthy adults were given oral zinc in a lower dose (0.69 mmol/day) for 12 weeks. Blood-samples were collected regularly and plasma zinc, plasma copper, and whole blood zinc were analysed by atomic-absorption spectro-

SIR,-Dr Hoogenraad and colleagues’ reported

NIGHT COUGH IN CHILDREN

SIR,-Dr Wind states (Feb. 17, p. 382) that "Ear, nose and throat surgeons and general practitioners know well that most children referred for adenoidectomy (in my patients 70-80%) have a dry night cough which disappears after surgery". A recent survey of consultant E.N.T. surgeons in the U.K. did not reveal one who felt that a patient referred for adenoidectomy suffered from a dry night cough.’ It does appear to be true, however, that the symptoms attributed to "adenoids" will disappear after surgery, but this happens irrespective of whether the adenoids are removed or not.2 University Department of Otorhino-laryngology, Royal Liverpool Hospital, Liverpool L7 8XP

P. M. STELL

an

photometry (see table). ZINC AND COPPER LEVELS

SiR,—Iwas interested

to read the correspondence 3,4 arising of the editorial on complications of oesophageal reflux.s I do agree with Dr Wind4that the cough reflex can be initiated by stimuli from various sites other than the larynx and trachea, and Amberson’s report6 did not state that postnasal secretions do not enter the larynx of children at night. Oesophageal reflux is known to cause cricopharyngeal muscle spasm and thus the postnasal secretion would find it difficult to "pass down the oesophagus". I also agree with the observation of Wind that we see many children with dry cough at night due to a postnasal

out

discharge. E.N.T.

Department, Dudley Road and Hallam Hospitals, Birmingham

AHMES L. PAHOR

DIURNAL VARIATION IN SYSTOLIC TIME INTERVAL

SiR,—Dr Fromer and colleagues (Feb. 20, p. 390) raise the

For Zn 1 mol/t-6.54

important question of spontaneous baseline variation of systolic time intervals (S.T.I.) with reference to long-term cardiotoxicity studies during drug therapy. Unfortunately, in this

;jLg/dt; for Cu 1 mo)/t=6- 35 ug/dl.

The increase in plasma-zinc was much less than in the first study in which the intake of zinc was three times higher. After 12 weeks, the zinc levels reached a peak of 19 umol/1. The striking thing, however, was that the plasma-copper decreased throughout the study, and the Cu:Zn ratio became significantly low towards the end of the investigation. During prolonged zinc therapy, copper absorption and transport seems to be affected considerably. Even during the initial stages of subclinical zinc deficiency, there is a reciprocal increase’of copper in plasma.3,4 Normally, the Cu:Zn ratio in plasma is 0-9-1.2and it increases in several clinical conditions (malignant diseases, acute and chronic infections) and with prolonged treatment with drugs, especially corticosteroids. The ratio rarely falls below 0.8. I think it is important to observe that copper levels in plasma are affected significantly during excess zinc intake other than from dietary sources. Dietary intake of copper form prepared foods in Sweden and other industrialised countries is much lower than the R.D.A. values.5 This factor may influence further the absorption and transport of copper during zinc therapy, especially in growing children and pregnant women. Department 2, University Hospital, S-221 85 Lund, Research

Sweden.

1.

M. ABDULLA

day. a detailed study on one healthy male volunteer, aged 30, found that, on 3 successive days, under a strict dietary and behavioural regimen, there was a distinct diurnal fluctuation

In

we

SUMMARY OF DIURNAL VARIATION

*Systolic time intervals were averaged over 3 days for each hour between 9 A.M. and 5 p.M.The difference between the maximum and minimum values for this "average" diurnal variation were then divided by their arithmetic mean to give the above values. in corrected pre-ejection period (P.E.P.c), corrected left-ventricular ejection-time (L.V.E.T.c)’ and true isovolumetric contraction time (T.LC.T.). If we use the same definition of A% as Fromer et al. used, and correct for heart-rate, but compare measurements taken at the same time of day, the variation (S.D.2R%) of 2R%P.E.P., is + S-43. It is encouraging to note that the value of A% was close to zero (-0-16). Corresponding values for 3.%L.V.E.T.c and 2K%T.I.C.T. were —0-78 ± 1.49 and

Hoogenraad, T. U., Vanden Hamer, C. J. A., Koevoct, R., de Ruyter Korver,

E.G.W.M. Lancet, 1978, ii, 1262. Abdulla, M., Svensson, S. Scand. J. Clin. Lab. Invest. (in the press). 3. Abdulla, M., Björklund, A., Mathur, A., Wallenius, K. J. surg Onc. (in the

2.

press). 4. 5.

short communication Fromer et al. did not state whether their "successive measurements" were made at the same time of

Mathur, A., Wallenius, K., Abdulla, M. Archs oral Biol. (in the press). Abdulla, M., Svensson, S. Scand. J. Gastroent. (in the press).

1. Hibbert, J. Clin. Otolar. 1978, 2, 239. 2. Hibbert, J., Stell, P. M. Lancet, 1978, i, 489. 3. Phelan, P. D. Lancet, 1978, ii, 1309. 4. Wind, J. ibid. 1979, i,382. 5. Lancet, 1978,ii,773. 6. Amberson, J. B. Bull. Johns Hopkins Hosp. 1954,

94, 227.