- Email: [email protected]
CLINICAL AND BIOCHEMICAL ABNORMALITIES IN COPPERSMITHS EXPOSED TO CADMIUM
396 this finding was the lack of Of V.L.D.L. triglycerides.
change
in the concentration
CLINICAL AND BIOCHEMICAL ABNORMALITIES IN COPPERSMITHS EXPOSED TO CADMIUM
Several workers, on the basis of epidemiological evidence, have suggested that the higher serum-lipids of in part attributable to a Possible mechanisms for such diet. fibre-depleted an effect are that fibre has a specific lipid-lowering action,15 16 18 or that fibre-rich unrefined foods are promoters of satiety and an obstacle to excessive calorie intake.19-22 Certainly, as shown in the present study, pectin added to the British diet in a dose of 12 g daily will modestly lower serum-cholesterol. However, in order to ingest 12 g of unrefined pectin daily, fruit equivalent to 1’2 kg of apples would have to be eaten.23 Many populations have serum-cholesterol concentrations much more than 7.9% less than those of the British population and their dietary intake of fruit would thus have to be enormous for their low serum-cholesterol to be explained by the cholesterol-lowering property of pectin. The same appears to be true of other dietary fibres so far investigated, which either like wheat bran do not reduce serum-cholesterol24-26 or like guar gum,3 10 lignin,27 cellulose,2s or psyllium seed (’Metamucil’)l9 may do so, but as with pectin only when given in apparently unphysiologically large amounts. Further study of vegetable fibres taken in pharmacological amounts may yield agents of value in the treatment of individual patients with hyperlipidaemia, but it would be premature to conclude that they have any specific lipid-lowering effect in amounts encountered in natural diets. In the case of pectin, whilst it is possible that it might be more potent in patients with hypercholesterolaemia, any therapeutic value would be severely limited by its distastefulness, which is even greater than that of currently available more
affluent
populations 13-18
P. J. PATERSON A. MCKIRDY G. S. FELL J. M. OTTOWAY O. P. FITZGERALD-FINCH F. E. R. HUSAIN A. LAMONT A. J. YATES S. ROXBURGH R. SCOTT E. A. MILLS
are
Royal Infirmary; Strathclyde University; and Employment Medical Advisory Service (Scotland), Glasgow
5(18.5%) of a group of 27 coppersmiths exposed to cadmium fume had stone disease. When compared with a control group of assembly workers in the same factory they had evidence of renal impairment as shown by blood biochemistry and proteinuria. A greater tendency to liver damage was found in the coppersmiths. There was evidence that restrictive airways disease was more common in the coppersmiths Summary
than in the control group. Blood-cadmium concentrations were significantly higher in the coppersmiths and in the assembly workers than in a reference population. Introduction THE results of clinical and biochemical investigations in 27 coppersmiths (group i) who were exposed to cadmium fumes during brazing operations (average length of employment 17.8years) were compared with those in 19 assembly workers (group II) who were similarly inves-
lipid-lowering agents. 1.
The lack of correlation between changes in stool weight and whole-gut transit-time and changes in lipids and lipoproteins suggest that these effects of pectin are not interrelated. The effect on serum-cholesterol may be related to bile-salt sequestration and to increased stoolfat content, as has been shown in rats.12 The effect of pectin on wet stool weight may result from an increase in stool water, as is the case for wheat bran, either as a consequence of unchanged pectin in the stool or of the presence of volatile acids formed by its bacterial decomposition." With regard to the latter possibility Werch and Ivy31 did not find a significant increase in the excretion of acetic or formic acid in normal subjects taking 30 g of pectin daily. However, they expressed their results in terms of wet stool weight, which as the present study has shown is increased by pectin. There was no significant change in whole-gut transittime when pectin was administered, and a similar finding has been reported for wheat bran.32 However, more recently consistent reductions in gut-transit time with wheat bran have been shown by a continuous marker method.33 Whether this will prove to be the case for pectin remains to be seen. We thank Mrs M.
Armstrong for technical assistance. This work partly supported by the South West Regional Health Authority. Requests for reprints should be addressed to P. N. D.
was
References at foot of next column
Keys, A., Grande, F., Anderson, J. T. Proc. Soc. exp. Biol. Med. 1961, 106, 555.
2. 3. 4.
Truswell, A. S., Kay, R. M. Lancet, 1975, i, 922. Jenkins, D. J. A., Leeds, A. R., Newton, C., Cummings, J. H. ibid. p 1116 Hinton, J. M., Lennard-Jones, J. E., Young, A. C. Gut, 1969, 10, 842 5. Robertson, G., Cramp, D. G. J. clin. Path. 1970, 23, 243. 6. Kessler, G., Lederer, H. in Automation in Analytical Chemistry 1, edited
by L. T. Skeggs). p. 341. 1965. Havel, R. J., Eder, H. A., Bragdon, J. H. J. clin. Invest. 1955, 34, 1345 Durrington, P. N., Whicher, J. T., Warren, C., Bolton, C. H., Hartog, M Clinica chim. Acta, (in the press). 9. Alaupovic, P., Lee, D. M., McConathy, W. J. Biochim. biophys. Acta, 1972 260, 689. 10. Fahrenbach, M. J., Riccardi, B. A., Saunders, J. C., Lourie, I. M, Heider J. G. Circulation, 1963, 31/32, suppl. II, 11. 11. Ershoff, B. H., Wells, A. F. Exp. Med. Surg. 1962, 20, 272. 12. Mokady, S. Nutr. Metab. 1973, 15, 290. 13. Walker, A. R. P., Arvidsson, U. B. J. clin. Invest. 1954, 33, 1358. 14. Bersohn, I., Walker, A. R. P., Higginson, J. S Afr. med. J 1956, 30, 411 15. Trowell, H. Am. J. clin. Nutr. 1972, 25, 926. 16. Trowell, H. Atherosclerosis, 1973, 16, 138. 17. Burkitt, D. P. Br. med. J. 1973, i, 274. 18. Burkitt, D. P., Walker, A. R. P., Painter, N. S. J. Am. med Ass 1974, 229. 7. 8.
1068. 19 Heaton, K. W. Lancet, 1973, ii, 1418. 20. Cleave, T. L. ibid. 1974, i, 137. 21. Cleave, T. L. in The Saccharine Disease. Bristol, 1974. 22. James, W. P. T., Cummings, J. H. Lancet, 1974, i, 61. 23. Buckle, F. J. Personal communication. 24. Durrington, P., Wicks, A. C. B., Heaton, K. W. Lancet, 1975, ii, 133 25. Lancet, 1975, ii, 353. 26. Truswell, A. S., Kay, R. M. Lancet, 1976, i, 367 27. Thiffault, C , Belanger, M., Pouliot, M. Can. med. Ass. J 1970, 103, 1 28. Shurpalekar, K. S., Doraiswamy, T. R., Sundaravalli, O. E., Narayana R
Nature, 1971, 232. 554. 29. Forman, D. T., Garvin, J. E., Forestner, J. E., Taylor, C. B. Proc. Soc e Biol. Med. 1968, 127, 1060. 30. Cummings, J. H. Gut, 1972, 14, 69. 31. Werch, S. C., Ivy, A. C. Am. J. Dis. Child. 1941, 62, 499. 32. Eastwood, M. A., Kirkpatrick, J. R., Bone, A., Hamilton, T Br 1973, iv, 392. 33. Cummings, J. H., Jenkins, D. J. A., Wiggins, H. S Gut, 1976, 17, 216
397
:,3ted, Men in group ii (average length of employment Q years) worked near to the coppersmiths and were .Simitar age and social background. Methods Each man was interviewed and his social, medical, and industrial history was recorded. A careful investigation of the MM target organs of cadmium toxicity was made by biochemical, vitalograph, and radiological means, including fullchest and abdominal radiographs. Each man collected a urine specimen (24 h), which was anahsed for protein content (quantitative and qualitative) and alcum, creatinine, and cadmium output. All cadmium determinations were made by a recently developed atomic fluorescence spectrophotometric technique.’ The procedure for blood collection was shown to be free from serious cadmium contamination. Blood-cadmium reference values were obtained from 98 blood-samples submitted for other routine analyses. L’rnary cadmium reference values were obtained by analysis of urine from 42 student volunteers. All other biochemical methods were standard procedures, and reference values were those routinely used in the biochemical laboratory.
Results Renal Abnormalities There was biochemical evidence of kidney involvement in group1 (27 men)-20 had increased plasma-urea and 13 had increased plasma-creatinine. 13 had possible renal acid/base imbalance as shown by raised plasma-chloride concentrations. Plasma-creatinine values in group II workers were significantly lower (P<0-03) than in group J. SIGNIFICANT STATISTICAL DIFFERENCES BETWEEN COPPERSMITHS
1,,CO.B’TROL WORKERS
(GROUP II), AND REFERENCE
(GROUP
pyelogram with tomography verify suspected stones. This showed, together with inspection of the men’s previous hospital records, that in group I, 5 out of 27 (18.5%) had or had had confirmed renal stones. In group ii only 1 out of 19 (5.4%) had renal stones. graphs, was
an
used
on
intravenous
doubtful
cases to
Liver Function
Only 5 sets of aminotransferase activities were increased in the plasma of the group-t workers, although increases in alanine aminotransferase (5 out of 27) did indicate a degree of hepatocellular damage. However, liver abnormalities were probably not widespread. Cardiopulmonary Function Blood-pressure.-Systolic and diastolic blood-presraised in 8 of the group-i men, and in 1 man systolic blood-pressure was increased Only 3 of the 19 men in group II had raised systolic pressure, and of these only 1 had a concomitant increase in diastolic pressure. Lung function.-Vitalographs were obtained by two observers, and included appropriate corrections for age and weight. In group i, 18 had forced expiratory volume/forced vital capacity ratios of less than 75%, and of these, 9 had evidence of restrictive airways disease and 4 had evidence of obstructive airways disease. 1 man had evidence of both respiratory problems. 11 of the coppersmiths were smokers, but no correlation was evident between smoking-habits, vitalograph results, and blood-cadmium concentrations. In the assembly workers, (group II), only 2 men had evidence of disordered lung function as revealed by vitalograph studies. sures were
VALUES FOR CERTAIN
Radiology
BIOCHEMICAL ESTIMATIONSS
In group i there was radiological evidence of chronic obstructive airways disease in 7 men and another 6 had pleural thickening. In group n, 4 men had evidence of obstructive disease and 4 had pleural thickening.
Calcium and Phosphorus Abnormalities
mmoVlin groupI andO.93:tO.36 mmol/l in group n, indicated possible tubular damage in the coppersmiths (see accompanying table).
Total serum-calcium concentration was normal in both groups. In group I, 13 out of 27 had lowered inorganic phosphate concentrations in blood plasma, and 3 of these had raised alkaline-phosphatase values. In one of these men an accompanying increase in alanine aminotransferase activity suggested that hepatic damage rather than an osteogenic cause was responsible for the abnormal alkaline-phosphatase concentration. An important result of these abnormalities was that 22 of the 27 men in group i had increased urinary calcium excretion.
l’rinary Protein
Cadmium Results
Similarly, plasma-phosphate, which
11 of the 27
was
0-78±0-18
in group t had significant proteinuria (110-1140 mg/24 h). None of the men in group ii had a positive reaction to the salicylphonic acid test for urine protein. Electrophoretic analysis of the protein :xcreted by the coppersmiths indicated that 7 had a nonselective glomerular proteinuria and 1 a mainly tubular eak of high molecular weight protein. In the remaining : cases the results were technically unsatisfactory. men
Stone Disease After separate checks
by two consultants of the radio-
Blood-cadmium concentrations in group i ranged from 7to25[jLg Cd/1 (mean IS.8±s.D. 5.4 }ig Cd/1), which was statistically significantly higher than the reference population (range 3-7 p.g Cd/1, mean 4.0+_1.0 p.g Cd/1). Workers in group it also had increased blood-cadmium values (mean 14.5±7.2 p.g Cd/1) compared to the reference population but there was no significant difference in blood-cadmium concentration between the two groups of workers studied. The urinary cadmium excretion in group I (37-1±19-2 g/1) was higher than that of the reference population (10·5±4·2 g Cd/1),
.
398
but the possibility of contamination of the urine samples by dust from the workers’ factory environment cannot be excluded, since other metals such as zinc and copper were also increased in samples from group II.
THE INFRASOUND BLOOD-PRESSURE RECORDER A CLINICAL EVALUATION R. C. EDWARDS R. BANNISTER
Discussion Cadmium toxicity manifests itself by the impairment of renal and pulmonary function, and liver and bone damage.2-9 Cadmium is probably a greater hazard than is generally realised because apart from its use in the alkaline battery industry, it is used in steel preservation. 10-14 Some household objects contain cadmium and these have been the source of overt poisoning. 11-17 Cigarette smoke is a source of cadmium,18 19 and will add to the body burden of cadmium in workers who may already be at risk industrially from the inhalation of cadmium fumes. In industrial premises death from cadmium poisoning is very rare but is much more likely to occur when ventilation is inadequate.2o Previous surveys have shown considerable abnormality in workers chronically exposed to cadmium, and one group suggested that prostatic carcinoma is more likely to occur in cadmium-exposed workers.21 22 This has not been substantiated, although there is some evidence that cadmium can induce carcinomatous change in laboratory animals.23 The men in the present study have undergone a simple clinical and biochemical screening process which it is hoped will be supplemented by more extensive inpatient analyses. There is quite clearly, however, a considerable amount of disease in the coppersmiths and if other causes for the biochemical abnormalities can fairly be excluded it may be deduced that cadmium poisoning had occurred and was manifest to some degree in a high proportion of the men involved. 18-5% of the coppersmiths had renal stone disease, a frequency similar to that reported by Friberg24 whc found renal stone disease in 20% of workers exposed to cadmium industrially. The increased concentrations of cadmium in the blood of the assembly workers in group ii also confirms their recent exposure to cadmium. Both groups of workers had on average spent the same time in the factory but there was less overt disease in group n, suggesting that the accumulation of cadmium is less in these workers. The difference between the groups could be explained by the fact that the coppersmiths art much closer to the cadmium fume while brazing. We thank Miss Hawthorne, Mrs Wilson, and Mr Ballantine fo) their help in this work and Dr Eric Blackadder of E.M.A.S. (Scotland: for helpful advice and criticism. Requests for reprints should be addressed to R.S., Urologica Department, Royal Infirmary, Glasgow G4 OSF.
Northwick Park
Hospital and Clinical Research Centre,
Harrow, Middlesex, and National Hospital for Nervous Diseases, Queen Square, London
Comparisons with direct recordings show that the Physiometrics automatic blood-pressure recorder does not accurately reflect intraarterial pressure and tends to over-read both systolic and diastolic pressures.
Summary
Introduction THE Physiometrics SR2 automatic blood-pressure recorder is said to be particularly useful where the blood-pressure is so low that Korotkoff sounds are difficult to detect. Many automatic instruments of this kmd have been marketed but few evaluations have been performed. We have compared the performance of this instrument with direct intra-arterial recordings.
Materials and Methods
.
The Physiometrics machine (fig. 1) employs a transducer built into an inflatable cuff, which is positioned over the brachial artery. Two cuffs are available: a rigid tube into which the arm is inserted, and a soft cuff which is wrapped around the arm in the usual fashion. Cuff inflation is automatic and the rate of deflation can be varied. In this study we followed the operating instructions marked on the machine and-used a cuff deflation-rate of 3 mm Hg per beat. A sensitivity control is also provided and this was set at 5. The transducer is sensitive to very-low-frequency vibrations (infrasound) which are amphfied and reproduced as an audio tone. The theory is that the collapsed vessel flutters when a pulse passes into it from the segment under the deflating cuff and this flutter gives rise to low-frequency vibrations in the arm tissues. When the cuff pressure falls below diastolic pressure the fluttering motion of the arterial wall ceases, as do the low-frequency vibrations.’1 For recording purposes, the audio tones are represented as movements of an ink stylus which writes on a flat rotating disc, Systolic pressure is ordinarily taken as the first of the pen movements and diastolic pressure as the last (fig. 2a). Occasionally the pen movement increases progressively to a maximum at the systolic end and decreases progressively to a minimum at the diastolic end. In these circumstances the manufacturers recommend that the first regular deflection be
10. 11. REFERENCES 1. Fell, C. S., Ottaway, J. M. Hussein, F. E. R. Unpublished. 2. Kazantsis, G., Flynn, F. V., Spoage, J. S., Trott, D. G. Q.
M. Br. med. bull. 1975, 31, 246. Kobayashi, K. 5th International Water Pollution Research Conference, Sec tion 1, p. 2511. San Francisco, 1970.
Webb,
12. Lancet, 1973, ii, 1134. 13. Harvey, T. C., McLellan,
Jl Med. 1963,
3. 4. 5.
32, 365. Perry, N. M. A. Lancet, 1959, ii, 463. Adams, R. G., Harrison, J. P., Scott, P. Q. Jl Med. 1969, 38, 425. Nordberg, G. F., Piscator, M., Nordberg, M. Acta Pharmac. tox. 1971, 30,
6.
Lauwerys,
289. R. R., Buchat, J. P., Roals, H. A., Brouers, J., Stanescu, D. Archs Environ. Hlth, 1976, 28, 145. 7. British Medical Journal, 1967, ii, 392. 8. Kobayashi, J. 5th Annual Conference on Trace Elements m the Environment; p. 117. Columbia, Missouri, 1971. 9. Itonawa, Y. A., Tabie, R., Tawaka, S. Archs environ. Hlth, 1974, 28, 149.
A. D. GOLDBERG E. B. RAFTERY
J. S., Thomas, B. J. Fremlin, J. S. ibid 197
i, 1269. 14. 15 16. 17. 18.
Friberg, L. J. indust. Hyg. 1948, 30, 32. Kennedy, C., Roe, F. J. C. Lancet, 1969, i, 1206. Frant, S., Kleeman, I. J. Am. med. Ass. 1941, 117, 86. Jenner, C. C., Cunningham, J. A. K. New Z. med. J. 1944, 43, 288 Nandi, M., Jick, H., Stone, D., Shapiro, S., Lewis, G. P. Lancet, 1972. 1329.
Lewis, G. P , Jusko, W. J., Couchlin, L. L., Harte, S. ibid. 1972, i, 291 Winston, R. N., Br. med. J. 1971, ii, 401. Potts, C. L. Ann. occup. Hyg. 1965, 8, 55. Kipling, M. D., Waterhouse, J. A. H. Lancet, 1967, i, 730. Scott, R , Aughey, E., McLaughlan, I. Trace Element Metabolism in mals; p. 690. Madison, Wisconsin, 1974. 24. Friberg, L. Acta med. scand. 1950, 238, suppl. 240.
19. 20. 21. 22. 23.
change
in the concentration
CLINICAL AND BIOCHEMICAL ABNORMALITIES IN COPPERSMITHS EXPOSED TO CADMIUM
Several workers, on the basis of epidemiological evidence, have suggested that the higher serum-lipids of in part attributable to a Possible mechanisms for such diet. fibre-depleted an effect are that fibre has a specific lipid-lowering action,15 16 18 or that fibre-rich unrefined foods are promoters of satiety and an obstacle to excessive calorie intake.19-22 Certainly, as shown in the present study, pectin added to the British diet in a dose of 12 g daily will modestly lower serum-cholesterol. However, in order to ingest 12 g of unrefined pectin daily, fruit equivalent to 1’2 kg of apples would have to be eaten.23 Many populations have serum-cholesterol concentrations much more than 7.9% less than those of the British population and their dietary intake of fruit would thus have to be enormous for their low serum-cholesterol to be explained by the cholesterol-lowering property of pectin. The same appears to be true of other dietary fibres so far investigated, which either like wheat bran do not reduce serum-cholesterol24-26 or like guar gum,3 10 lignin,27 cellulose,2s or psyllium seed (’Metamucil’)l9 may do so, but as with pectin only when given in apparently unphysiologically large amounts. Further study of vegetable fibres taken in pharmacological amounts may yield agents of value in the treatment of individual patients with hyperlipidaemia, but it would be premature to conclude that they have any specific lipid-lowering effect in amounts encountered in natural diets. In the case of pectin, whilst it is possible that it might be more potent in patients with hypercholesterolaemia, any therapeutic value would be severely limited by its distastefulness, which is even greater than that of currently available more
affluent
populations 13-18
P. J. PATERSON A. MCKIRDY G. S. FELL J. M. OTTOWAY O. P. FITZGERALD-FINCH F. E. R. HUSAIN A. LAMONT A. J. YATES S. ROXBURGH R. SCOTT E. A. MILLS
are
Royal Infirmary; Strathclyde University; and Employment Medical Advisory Service (Scotland), Glasgow
5(18.5%) of a group of 27 coppersmiths exposed to cadmium fume had stone disease. When compared with a control group of assembly workers in the same factory they had evidence of renal impairment as shown by blood biochemistry and proteinuria. A greater tendency to liver damage was found in the coppersmiths. There was evidence that restrictive airways disease was more common in the coppersmiths Summary
than in the control group. Blood-cadmium concentrations were significantly higher in the coppersmiths and in the assembly workers than in a reference population. Introduction THE results of clinical and biochemical investigations in 27 coppersmiths (group i) who were exposed to cadmium fumes during brazing operations (average length of employment 17.8years) were compared with those in 19 assembly workers (group II) who were similarly inves-
lipid-lowering agents. 1.
The lack of correlation between changes in stool weight and whole-gut transit-time and changes in lipids and lipoproteins suggest that these effects of pectin are not interrelated. The effect on serum-cholesterol may be related to bile-salt sequestration and to increased stoolfat content, as has been shown in rats.12 The effect of pectin on wet stool weight may result from an increase in stool water, as is the case for wheat bran, either as a consequence of unchanged pectin in the stool or of the presence of volatile acids formed by its bacterial decomposition." With regard to the latter possibility Werch and Ivy31 did not find a significant increase in the excretion of acetic or formic acid in normal subjects taking 30 g of pectin daily. However, they expressed their results in terms of wet stool weight, which as the present study has shown is increased by pectin. There was no significant change in whole-gut transittime when pectin was administered, and a similar finding has been reported for wheat bran.32 However, more recently consistent reductions in gut-transit time with wheat bran have been shown by a continuous marker method.33 Whether this will prove to be the case for pectin remains to be seen. We thank Mrs M.
Armstrong for technical assistance. This work partly supported by the South West Regional Health Authority. Requests for reprints should be addressed to P. N. D.
was
References at foot of next column
Keys, A., Grande, F., Anderson, J. T. Proc. Soc. exp. Biol. Med. 1961, 106, 555.
2. 3. 4.
Truswell, A. S., Kay, R. M. Lancet, 1975, i, 922. Jenkins, D. J. A., Leeds, A. R., Newton, C., Cummings, J. H. ibid. p 1116 Hinton, J. M., Lennard-Jones, J. E., Young, A. C. Gut, 1969, 10, 842 5. Robertson, G., Cramp, D. G. J. clin. Path. 1970, 23, 243. 6. Kessler, G., Lederer, H. in Automation in Analytical Chemistry 1, edited
by L. T. Skeggs). p. 341. 1965. Havel, R. J., Eder, H. A., Bragdon, J. H. J. clin. Invest. 1955, 34, 1345 Durrington, P. N., Whicher, J. T., Warren, C., Bolton, C. H., Hartog, M Clinica chim. Acta, (in the press). 9. Alaupovic, P., Lee, D. M., McConathy, W. J. Biochim. biophys. Acta, 1972 260, 689. 10. Fahrenbach, M. J., Riccardi, B. A., Saunders, J. C., Lourie, I. M, Heider J. G. Circulation, 1963, 31/32, suppl. II, 11. 11. Ershoff, B. H., Wells, A. F. Exp. Med. Surg. 1962, 20, 272. 12. Mokady, S. Nutr. Metab. 1973, 15, 290. 13. Walker, A. R. P., Arvidsson, U. B. J. clin. Invest. 1954, 33, 1358. 14. Bersohn, I., Walker, A. R. P., Higginson, J. S Afr. med. J 1956, 30, 411 15. Trowell, H. Am. J. clin. Nutr. 1972, 25, 926. 16. Trowell, H. Atherosclerosis, 1973, 16, 138. 17. Burkitt, D. P. Br. med. J. 1973, i, 274. 18. Burkitt, D. P., Walker, A. R. P., Painter, N. S. J. Am. med Ass 1974, 229. 7. 8.
1068. 19 Heaton, K. W. Lancet, 1973, ii, 1418. 20. Cleave, T. L. ibid. 1974, i, 137. 21. Cleave, T. L. in The Saccharine Disease. Bristol, 1974. 22. James, W. P. T., Cummings, J. H. Lancet, 1974, i, 61. 23. Buckle, F. J. Personal communication. 24. Durrington, P., Wicks, A. C. B., Heaton, K. W. Lancet, 1975, ii, 133 25. Lancet, 1975, ii, 353. 26. Truswell, A. S., Kay, R. M. Lancet, 1976, i, 367 27. Thiffault, C , Belanger, M., Pouliot, M. Can. med. Ass. J 1970, 103, 1 28. Shurpalekar, K. S., Doraiswamy, T. R., Sundaravalli, O. E., Narayana R
Nature, 1971, 232. 554. 29. Forman, D. T., Garvin, J. E., Forestner, J. E., Taylor, C. B. Proc. Soc e Biol. Med. 1968, 127, 1060. 30. Cummings, J. H. Gut, 1972, 14, 69. 31. Werch, S. C., Ivy, A. C. Am. J. Dis. Child. 1941, 62, 499. 32. Eastwood, M. A., Kirkpatrick, J. R., Bone, A., Hamilton, T Br 1973, iv, 392. 33. Cummings, J. H., Jenkins, D. J. A., Wiggins, H. S Gut, 1976, 17, 216
397
:,3ted, Men in group ii (average length of employment Q years) worked near to the coppersmiths and were .Simitar age and social background. Methods Each man was interviewed and his social, medical, and industrial history was recorded. A careful investigation of the MM target organs of cadmium toxicity was made by biochemical, vitalograph, and radiological means, including fullchest and abdominal radiographs. Each man collected a urine specimen (24 h), which was anahsed for protein content (quantitative and qualitative) and alcum, creatinine, and cadmium output. All cadmium determinations were made by a recently developed atomic fluorescence spectrophotometric technique.’ The procedure for blood collection was shown to be free from serious cadmium contamination. Blood-cadmium reference values were obtained from 98 blood-samples submitted for other routine analyses. L’rnary cadmium reference values were obtained by analysis of urine from 42 student volunteers. All other biochemical methods were standard procedures, and reference values were those routinely used in the biochemical laboratory.
Results Renal Abnormalities There was biochemical evidence of kidney involvement in group1 (27 men)-20 had increased plasma-urea and 13 had increased plasma-creatinine. 13 had possible renal acid/base imbalance as shown by raised plasma-chloride concentrations. Plasma-creatinine values in group II workers were significantly lower (P<0-03) than in group J. SIGNIFICANT STATISTICAL DIFFERENCES BETWEEN COPPERSMITHS
1,,CO.B’TROL WORKERS
(GROUP II), AND REFERENCE
(GROUP
pyelogram with tomography verify suspected stones. This showed, together with inspection of the men’s previous hospital records, that in group I, 5 out of 27 (18.5%) had or had had confirmed renal stones. In group ii only 1 out of 19 (5.4%) had renal stones. graphs, was
an
used
on
intravenous
doubtful
cases to
Liver Function
Only 5 sets of aminotransferase activities were increased in the plasma of the group-t workers, although increases in alanine aminotransferase (5 out of 27) did indicate a degree of hepatocellular damage. However, liver abnormalities were probably not widespread. Cardiopulmonary Function Blood-pressure.-Systolic and diastolic blood-presraised in 8 of the group-i men, and in 1 man systolic blood-pressure was increased Only 3 of the 19 men in group II had raised systolic pressure, and of these only 1 had a concomitant increase in diastolic pressure. Lung function.-Vitalographs were obtained by two observers, and included appropriate corrections for age and weight. In group i, 18 had forced expiratory volume/forced vital capacity ratios of less than 75%, and of these, 9 had evidence of restrictive airways disease and 4 had evidence of obstructive airways disease. 1 man had evidence of both respiratory problems. 11 of the coppersmiths were smokers, but no correlation was evident between smoking-habits, vitalograph results, and blood-cadmium concentrations. In the assembly workers, (group II), only 2 men had evidence of disordered lung function as revealed by vitalograph studies. sures were
VALUES FOR CERTAIN
Radiology
BIOCHEMICAL ESTIMATIONSS
In group i there was radiological evidence of chronic obstructive airways disease in 7 men and another 6 had pleural thickening. In group n, 4 men had evidence of obstructive disease and 4 had pleural thickening.
Calcium and Phosphorus Abnormalities
mmoVlin groupI andO.93:tO.36 mmol/l in group n, indicated possible tubular damage in the coppersmiths (see accompanying table).
Total serum-calcium concentration was normal in both groups. In group I, 13 out of 27 had lowered inorganic phosphate concentrations in blood plasma, and 3 of these had raised alkaline-phosphatase values. In one of these men an accompanying increase in alanine aminotransferase activity suggested that hepatic damage rather than an osteogenic cause was responsible for the abnormal alkaline-phosphatase concentration. An important result of these abnormalities was that 22 of the 27 men in group i had increased urinary calcium excretion.
l’rinary Protein
Cadmium Results
Similarly, plasma-phosphate, which
11 of the 27
was
0-78±0-18
in group t had significant proteinuria (110-1140 mg/24 h). None of the men in group ii had a positive reaction to the salicylphonic acid test for urine protein. Electrophoretic analysis of the protein :xcreted by the coppersmiths indicated that 7 had a nonselective glomerular proteinuria and 1 a mainly tubular eak of high molecular weight protein. In the remaining : cases the results were technically unsatisfactory. men
Stone Disease After separate checks
by two consultants of the radio-
Blood-cadmium concentrations in group i ranged from 7to25[jLg Cd/1 (mean IS.8±s.D. 5.4 }ig Cd/1), which was statistically significantly higher than the reference population (range 3-7 p.g Cd/1, mean 4.0+_1.0 p.g Cd/1). Workers in group it also had increased blood-cadmium values (mean 14.5±7.2 p.g Cd/1) compared to the reference population but there was no significant difference in blood-cadmium concentration between the two groups of workers studied. The urinary cadmium excretion in group I (37-1±19-2 g/1) was higher than that of the reference population (10·5±4·2 g Cd/1),
.
398
but the possibility of contamination of the urine samples by dust from the workers’ factory environment cannot be excluded, since other metals such as zinc and copper were also increased in samples from group II.
THE INFRASOUND BLOOD-PRESSURE RECORDER A CLINICAL EVALUATION R. C. EDWARDS R. BANNISTER
Discussion Cadmium toxicity manifests itself by the impairment of renal and pulmonary function, and liver and bone damage.2-9 Cadmium is probably a greater hazard than is generally realised because apart from its use in the alkaline battery industry, it is used in steel preservation. 10-14 Some household objects contain cadmium and these have been the source of overt poisoning. 11-17 Cigarette smoke is a source of cadmium,18 19 and will add to the body burden of cadmium in workers who may already be at risk industrially from the inhalation of cadmium fumes. In industrial premises death from cadmium poisoning is very rare but is much more likely to occur when ventilation is inadequate.2o Previous surveys have shown considerable abnormality in workers chronically exposed to cadmium, and one group suggested that prostatic carcinoma is more likely to occur in cadmium-exposed workers.21 22 This has not been substantiated, although there is some evidence that cadmium can induce carcinomatous change in laboratory animals.23 The men in the present study have undergone a simple clinical and biochemical screening process which it is hoped will be supplemented by more extensive inpatient analyses. There is quite clearly, however, a considerable amount of disease in the coppersmiths and if other causes for the biochemical abnormalities can fairly be excluded it may be deduced that cadmium poisoning had occurred and was manifest to some degree in a high proportion of the men involved. 18-5% of the coppersmiths had renal stone disease, a frequency similar to that reported by Friberg24 whc found renal stone disease in 20% of workers exposed to cadmium industrially. The increased concentrations of cadmium in the blood of the assembly workers in group ii also confirms their recent exposure to cadmium. Both groups of workers had on average spent the same time in the factory but there was less overt disease in group n, suggesting that the accumulation of cadmium is less in these workers. The difference between the groups could be explained by the fact that the coppersmiths art much closer to the cadmium fume while brazing. We thank Miss Hawthorne, Mrs Wilson, and Mr Ballantine fo) their help in this work and Dr Eric Blackadder of E.M.A.S. (Scotland: for helpful advice and criticism. Requests for reprints should be addressed to R.S., Urologica Department, Royal Infirmary, Glasgow G4 OSF.
Northwick Park
Hospital and Clinical Research Centre,
Harrow, Middlesex, and National Hospital for Nervous Diseases, Queen Square, London
Comparisons with direct recordings show that the Physiometrics automatic blood-pressure recorder does not accurately reflect intraarterial pressure and tends to over-read both systolic and diastolic pressures.
Summary
Introduction THE Physiometrics SR2 automatic blood-pressure recorder is said to be particularly useful where the blood-pressure is so low that Korotkoff sounds are difficult to detect. Many automatic instruments of this kmd have been marketed but few evaluations have been performed. We have compared the performance of this instrument with direct intra-arterial recordings.
Materials and Methods
.
The Physiometrics machine (fig. 1) employs a transducer built into an inflatable cuff, which is positioned over the brachial artery. Two cuffs are available: a rigid tube into which the arm is inserted, and a soft cuff which is wrapped around the arm in the usual fashion. Cuff inflation is automatic and the rate of deflation can be varied. In this study we followed the operating instructions marked on the machine and-used a cuff deflation-rate of 3 mm Hg per beat. A sensitivity control is also provided and this was set at 5. The transducer is sensitive to very-low-frequency vibrations (infrasound) which are amphfied and reproduced as an audio tone. The theory is that the collapsed vessel flutters when a pulse passes into it from the segment under the deflating cuff and this flutter gives rise to low-frequency vibrations in the arm tissues. When the cuff pressure falls below diastolic pressure the fluttering motion of the arterial wall ceases, as do the low-frequency vibrations.’1 For recording purposes, the audio tones are represented as movements of an ink stylus which writes on a flat rotating disc, Systolic pressure is ordinarily taken as the first of the pen movements and diastolic pressure as the last (fig. 2a). Occasionally the pen movement increases progressively to a maximum at the systolic end and decreases progressively to a minimum at the diastolic end. In these circumstances the manufacturers recommend that the first regular deflection be
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