- Email: [email protected]
MACROCYTOSIS OF CHRONIC ALCOHOLISM
1297
with infusion of 0-16 N HCl in 5% dextrose (598 mosmol. per litre.) via a central venous catheter. Of course there is one basic difference between Dr Whelton’s research observations and the results of therapy referred to in the editorial. The infusion of HCl in the former situation is to purposely induce an acidosis in dogs which start off with a normal pH, whilst in the editorial reference is made to HCl being infused therapeutically to restore an alkalosis in patients back to a normal pH. Increased haemolysis has been described in the presence of acidosis, but not alkalosis due to red-cell-enzyme inhibition.2,3 We would disagree with Dr Whelton concerning the safety of NH4Cl solutions in patients with gross metabolic alkalosis plus hepatic insufficiency (such as referred to in the editorial) or of NaCl solutions in patients with metabolic alkalosis plus sodium-retaining states. In both these situations we believe that HCl would be contrariwise safe. Division of Clinical Chemistry, Institute of Medical and
Veterinary Science, Adelaide, South Australia. Intensive Care Unit, Anaesthetics Department, Royal Adelaide Hospital, Adelaide, South Australia.
ROY W. PAIN.
L. WORTHLEY.
PATHOGENS IN THE URINARY TRACT SIR,—May I comment on Dr Maskell’s Occasional Survey (June 8, p. 1155) ? First, she rightly draws attention to the importance of quantitative colony-counts in determining if organisms cultured after catheterisation or suprapubic aspiration (S.P.A.) are contaminants. But of the three references cited for S.P.A., one 4 mentions colony-counts and S.P.A. but does not mention the use of one with the other. A second 5 mentions the use of colonycounts on urine obtained from S.P.A. but gives no results. Indeed these authors state later that " because the urine was obtained by S.P.A. colony-counts are unnecessary". The possibility of contamination of urine cultures obtained by S.P.A. with common skin commensals, such as coagulasenegative staphylococci, remains very real. Second, in ideal conditions when so-called midstream urines (M.S.U.) are obtained from women, cultures yielding a pure growth of more than 100,000 organisms per ml. will give about 5% false-positive results. In her survey, the specimens were obtained in the less than ideal conditions of domiciliary practice and she chose to select as " positive " or " showing definite infection " those specimens which gave pure growths of greater than 10,000 organisms per ml. The two factors together will undoubtedly increase the proportion of false positives to an extent that cannot be quantified, but must, I submit, seriously detract from the validity of her conclusions. Third, most of the 10,065 M.s.u. specimens will have come from women who might have been menstruating. With the average menstrual cycle there is a 1-in-5 (20%) chance that microscopic hasmaturia (which she does not define) will occur by simple contamination without any red cells being derived from the urinary tract. Unless it is possible to exclude all specimens obtained from women during or for 2-3 days after menstruation, it is not justifiable to conclude that microscopic hasmaturia and " gross " pyuria indicate acute inflammation of the urinary tract. North Ormesby Hospital, North Ormesby,
Middlesbrough, Teesside TS3 6HJ. 2. 3. 4.
** * This letter
was
shown
to
Dr
Maskell, whose reply
follows.—ED. L.
SIR,—In considering the significance of organisms cultured after catheterisation, my purpose was to point out that the method of inoculation of catheter specimens into liquid media and subsequent culture gave misleading results. So far as I know this method is never used now. My own experience of suprapubic aspiration specimens, which have been principally from babies and young children, is that contamination with skin commensals is extremely rare; having cultured several hundred of such specimens I cannot remember ever seeing it. I agree with Dove et al. that colony-counts are unnecessary in suprapubic aspiration specimens; the possibility of contamination will be revealed by a mixed growth provided that a suitable culture medium which grows commensals is used. The usual numerical criteria of significance should not be applied because, especially in adults, a diuresis must be induced in order to make suprapubic aspiration technically possible, and the count of organisms may thereby be considerably reduced. I think Mr Hole’s second point is answered by the figures given in my table 11. We are fortunate in this laboratory to serve an area in which the general practitioners are interested in urinary infection, and very conscientious about ensuring that midstream urines are carefully collected. We are also able to provide good specimen collection and refrigeration facilities. Since only 25% of the total number of specimens were classified as positive, and since nearly 60% were sterile on culture, I do not think that the false-positive rate is very high. Lastly, although I agree with Mr Hole that M.S.U. specimens from women who are menstruating may be contaminated with red and white cells, the culture will invariably show a mixed growth of contaminant and commensal organisms provided that a medium such as CLED is used. These specimens will all have been placed in the " doubtful " category and therefore not included in the figures for comparison of pyuria and hsematuria. Public Health Laboratory, St. Mary’s General Hospital, East Wing, Milton Road, R. M. MASKELL. Portsmouth P03 6AQ. MACROCYTOSIS OF CHRONIC ALCOHOLISM SIR,—Dr Wu and his colleagues (May 4, p. 829) report the direct effect of alcohol in producing macrocytosis unrelated to low folate or megaloblastic hsemopoiesis. A third of their cases, however, showed megaloblastic change associated with low folate. The reasons for low folate in alcoholics are not entirely clear, but they could be due to dietary insufficiency, an effect of alcohol on folate absorption, a direct anti-folate effect of alcohol, enhanced utilisation of folate as a co-factor in liver-enzyme activity or a combination of these reasons. Alcohol is a known inducer of liver enzymes1 and has a direct folate-lowering effect.2 A similar acute effect is seen with phenytoin and has been thought to be due to liverenzyme induction.3 In treated epileptics, low folate has been shown to correlate with hepatic microsomal enzyme induction as assessed by the urinary excretion of D-glucaric acid4 which acts as a marker of such enhancement. It would have been of interest to know whether there was any such correlation in the group of patients with low folate.
ROGER HOLE.
Murphy, J. R., J. Lab. clin. Med. 1967, 69, 758. Nathan, D. G., Segel, G. B. Postgrad. Med. 1971, 47, 179. Bailey, R. R., Roberts, A. P., Gower, P. E., de Wardener, H. E. Lancet, 1971, ii, 1112. 5. Dove, G. A., Bailey, A. J., Gower, P. E., Roberts, A. P., de Wardener, H. E. ibid. 1972, ii, 1281.
General Hospital, Steelhouse Lane,
Birmingham, B4 6NH.
J. SCOTT.
1. Lieber, C. S., De Carli, L. M. Science, N. Y. 1968, 162, 919. 2. Eichner, E. R., Hillman, R. S. J. clin. Invest. 1973, 53, 584. 3. Richens, A., Waters, A. H. Br. J. Pharmac. 1971, 41, 414. 4. Maxwell, J. D., Hunter, J., Stewart, D. A., Ardeman, S., Williams, R. Br. med. J. 1972, i, 297.
with infusion of 0-16 N HCl in 5% dextrose (598 mosmol. per litre.) via a central venous catheter. Of course there is one basic difference between Dr Whelton’s research observations and the results of therapy referred to in the editorial. The infusion of HCl in the former situation is to purposely induce an acidosis in dogs which start off with a normal pH, whilst in the editorial reference is made to HCl being infused therapeutically to restore an alkalosis in patients back to a normal pH. Increased haemolysis has been described in the presence of acidosis, but not alkalosis due to red-cell-enzyme inhibition.2,3 We would disagree with Dr Whelton concerning the safety of NH4Cl solutions in patients with gross metabolic alkalosis plus hepatic insufficiency (such as referred to in the editorial) or of NaCl solutions in patients with metabolic alkalosis plus sodium-retaining states. In both these situations we believe that HCl would be contrariwise safe. Division of Clinical Chemistry, Institute of Medical and
Veterinary Science, Adelaide, South Australia. Intensive Care Unit, Anaesthetics Department, Royal Adelaide Hospital, Adelaide, South Australia.
ROY W. PAIN.
L. WORTHLEY.
PATHOGENS IN THE URINARY TRACT SIR,—May I comment on Dr Maskell’s Occasional Survey (June 8, p. 1155) ? First, she rightly draws attention to the importance of quantitative colony-counts in determining if organisms cultured after catheterisation or suprapubic aspiration (S.P.A.) are contaminants. But of the three references cited for S.P.A., one 4 mentions colony-counts and S.P.A. but does not mention the use of one with the other. A second 5 mentions the use of colonycounts on urine obtained from S.P.A. but gives no results. Indeed these authors state later that " because the urine was obtained by S.P.A. colony-counts are unnecessary". The possibility of contamination of urine cultures obtained by S.P.A. with common skin commensals, such as coagulasenegative staphylococci, remains very real. Second, in ideal conditions when so-called midstream urines (M.S.U.) are obtained from women, cultures yielding a pure growth of more than 100,000 organisms per ml. will give about 5% false-positive results. In her survey, the specimens were obtained in the less than ideal conditions of domiciliary practice and she chose to select as " positive " or " showing definite infection " those specimens which gave pure growths of greater than 10,000 organisms per ml. The two factors together will undoubtedly increase the proportion of false positives to an extent that cannot be quantified, but must, I submit, seriously detract from the validity of her conclusions. Third, most of the 10,065 M.s.u. specimens will have come from women who might have been menstruating. With the average menstrual cycle there is a 1-in-5 (20%) chance that microscopic hasmaturia (which she does not define) will occur by simple contamination without any red cells being derived from the urinary tract. Unless it is possible to exclude all specimens obtained from women during or for 2-3 days after menstruation, it is not justifiable to conclude that microscopic hasmaturia and " gross " pyuria indicate acute inflammation of the urinary tract. North Ormesby Hospital, North Ormesby,
Middlesbrough, Teesside TS3 6HJ. 2. 3. 4.
** * This letter
was
shown
to
Dr
Maskell, whose reply
follows.—ED. L.
SIR,—In considering the significance of organisms cultured after catheterisation, my purpose was to point out that the method of inoculation of catheter specimens into liquid media and subsequent culture gave misleading results. So far as I know this method is never used now. My own experience of suprapubic aspiration specimens, which have been principally from babies and young children, is that contamination with skin commensals is extremely rare; having cultured several hundred of such specimens I cannot remember ever seeing it. I agree with Dove et al. that colony-counts are unnecessary in suprapubic aspiration specimens; the possibility of contamination will be revealed by a mixed growth provided that a suitable culture medium which grows commensals is used. The usual numerical criteria of significance should not be applied because, especially in adults, a diuresis must be induced in order to make suprapubic aspiration technically possible, and the count of organisms may thereby be considerably reduced. I think Mr Hole’s second point is answered by the figures given in my table 11. We are fortunate in this laboratory to serve an area in which the general practitioners are interested in urinary infection, and very conscientious about ensuring that midstream urines are carefully collected. We are also able to provide good specimen collection and refrigeration facilities. Since only 25% of the total number of specimens were classified as positive, and since nearly 60% were sterile on culture, I do not think that the false-positive rate is very high. Lastly, although I agree with Mr Hole that M.S.U. specimens from women who are menstruating may be contaminated with red and white cells, the culture will invariably show a mixed growth of contaminant and commensal organisms provided that a medium such as CLED is used. These specimens will all have been placed in the " doubtful " category and therefore not included in the figures for comparison of pyuria and hsematuria. Public Health Laboratory, St. Mary’s General Hospital, East Wing, Milton Road, R. M. MASKELL. Portsmouth P03 6AQ. MACROCYTOSIS OF CHRONIC ALCOHOLISM SIR,—Dr Wu and his colleagues (May 4, p. 829) report the direct effect of alcohol in producing macrocytosis unrelated to low folate or megaloblastic hsemopoiesis. A third of their cases, however, showed megaloblastic change associated with low folate. The reasons for low folate in alcoholics are not entirely clear, but they could be due to dietary insufficiency, an effect of alcohol on folate absorption, a direct anti-folate effect of alcohol, enhanced utilisation of folate as a co-factor in liver-enzyme activity or a combination of these reasons. Alcohol is a known inducer of liver enzymes1 and has a direct folate-lowering effect.2 A similar acute effect is seen with phenytoin and has been thought to be due to liverenzyme induction.3 In treated epileptics, low folate has been shown to correlate with hepatic microsomal enzyme induction as assessed by the urinary excretion of D-glucaric acid4 which acts as a marker of such enhancement. It would have been of interest to know whether there was any such correlation in the group of patients with low folate.
ROGER HOLE.
Murphy, J. R., J. Lab. clin. Med. 1967, 69, 758. Nathan, D. G., Segel, G. B. Postgrad. Med. 1971, 47, 179. Bailey, R. R., Roberts, A. P., Gower, P. E., de Wardener, H. E. Lancet, 1971, ii, 1112. 5. Dove, G. A., Bailey, A. J., Gower, P. E., Roberts, A. P., de Wardener, H. E. ibid. 1972, ii, 1281.
General Hospital, Steelhouse Lane,
Birmingham, B4 6NH.
J. SCOTT.
1. Lieber, C. S., De Carli, L. M. Science, N. Y. 1968, 162, 919. 2. Eichner, E. R., Hillman, R. S. J. clin. Invest. 1973, 53, 584. 3. Richens, A., Waters, A. H. Br. J. Pharmac. 1971, 41, 414. 4. Maxwell, J. D., Hunter, J., Stewart, D. A., Ardeman, S., Williams, R. Br. med. J. 1972, i, 297.