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LEAD ABSORPTION AND LEAD POISONING
811 this action of sulphapyridine can be inhibited by low concentrations of p-aminobenzoic acid or by larger amounts of nicotinic acid and its derivatives, or by an unknown substance in liver extracts. It is not yet clear which stage in the utilisation of nicotinamide is upset by sulphapyridine, but Teply and his colleagues consider that sulphapyridine does not act by preventing the synthesis of nicotinamide into its more complex derivatives, the coenzymes. The interference with p-aminobenzoic acid accounts for a large part of the therapeutic effect of sulphonamides, but it is not the whole story. LEAD
ABSORPTION
AND
LEAD
POISONING
BEFORE the war there were more than 1500 workers in the lead industries of this country, and 150,000 painters. Today there are probably many more, and it is important that they should be safeguarded against poisoning. Absorption and poisoning are not synonymous, for many workers absorb a considerable amount of lead without developing symptoms. In the early stages the commonest symptoms are weakness, loss of weight, constipation and colic, and the most useful sign is the contrast between apparent muscular development and actual physical power. In the absence of later signs such as wrist drop, blue line on the gums and stippling of the red cells, the diagnosis of poisoning is a matter of clinical judgment not subject to proof. Buxellstates that the threshold limit for long exposure to lead and its compounds in the air is 1-5 mg. of lead per 10 cubic metres of air ; and work by Dreesen2 in 13 storage-battery plants east of the Mississippi River confirms this. He showed that among 776 workmen albuminuria and symptoms of early plumbism were most common in those exposed to the highest atmospheric lead concentration. Generally speaking, the urinary and blood lead estimations, reticulocyte, stipple-cell and polychromatophilia values also varied with the atmospheric lead concentrations. Employees who had an average lead exposure of more than 3 mg. per 10 cm. were smelters, pasters, oxide mixers, group assemblers, plate driers, finishers, and repairers. The prevalence of arterial hypertension among these employees was not significantly different from that observed in other industrial workers. Cholak and Bambach 3 found that in 1052 normal persons with no occupational lead hazard the mean lead concentrations were 0-030 mg. per 100 g. of blood, 0-027 mg. per litre of urine and 0.28 mg. per 24 hours" sample of faeces. Exposure to lead in industry raises these values, and the corresponding figures for 86 men engaged in making white lead were 0-086, 0.241 and 3-76. Data from representative groups of workmen may therefore be used to find out the character of exposure in a plant, to measure the uniformity and efficacy of the means employed to control the exposure and to establish whether it is uniform in severity ; and this exposure may be correlated with the atmospheric lead concentration. Working with Kehoe and others, the same observers 4 have shown that, excretion is much slower than accumulation, and that risk of poisoning can be reduced by alternating a period of exposure with a longer period of non-exposure. More absorbed lead is excreted in the urine than in the faeces, and since adequate urinary excretion depends on adequate intake of fluid, a supply of palatable water is important in an industrial plant. Constipation, since it is said to increase the absorption of lead from the gut, should also be avoided. Between 1900 and 1933 the mortality-rate from lead poisoning in the United States fell from 3-1 per million to 0-7, thanks mainly to improved methods of control and good personal.hygiene. The estimations, now 1. Buxell, J. J. industr. Hyg. 1943, 25, 35. 2. Dreesen, W. C. Ibid, p. 60. 3. Cholak, J. and Bambach, K. Ibid, p. 47. 4. Kehoe, R. A. Ibid ; Cholak, J., Hubbard, D. M., and McNary, R. R. Ibid, p. 71.
Bambach, K.
used in conjunction with stipple-cell counts, mark another advance in the control of this hazard; and there is good reason to hope that the condition will soon be obsolete and curative treatment no lounger necessary. Hunter and Aub5 showed that repeated injections of parathyroid extract in 6 patients with chronic lead poisoning rapidly and effectively mobilised some of the stored lead from the bones, and they confirmed a striking parallelism between the storage and excretion of lead and calcium. Kehoe and his colleagues,44 judging from one case examined over short periods, doubt whether elimination of lead from the body can be much accelerated by artificial means ; but this opinion is not acceptable without much more evidence.
suggested,
RENAL FUNCTION AFTER CRUSHING INJURY IN Britain at present opportunities for clinical investigation of crush syndrome are fortunately rare, but experimental work may shed some light on the mechanism of the renal injury or perhaps suggest methods of investigating such cases in man. In an ingenious series of experiments,6 a group of workers at University College have analysed in detail the depression of renal function they were able to produce in the anaesthetised animal-by crushing and hammering the tightly bound limb and then keeping it bloodless for 5 hours. Their main criterion was creatinine clearance, which was found to fall considerablv within a few minutes of release of the compressing tubing. This fall was followed by a period of anuria and low blood-pressure ; if urinary flow was then stimulated and blood-pressure raised by intravenous fluids of various kinds, the creatinine clearance rose, but only to half normal. At the same time the urine became acid and contained pigment and casts. The mechanism
of this damage was investigated by partial obstruction of the ureter on one side. This procedure,. by cutting down urine now, might be expected to concentrate any filtered toxin in the tubules ; but in four experiments there was no significantly increased damage. In the fifth experiment the measure even seemed to protect the kidney, for the creatinine clearance was higher after the obstruction was removed than on the control side. The damage was not due to anuria since it was still produced when diuretics maintained a flow throughout : it was not due to low arterial tension, since after histamine injection (with resultant hypotension and anuria), there was no such damage. The kidneys showed no ’structural lesion in any way comparable to the changes in man ; even the mitochondria were intact except in one animal which developed irreversible anuria. In particular, there was no histological evidence for blockage ; nor were the kidneys tense as they should have been if either blockage or poisoning of tubular epithelium alone had been responsible. It would be interesting to know if the hammering, either alone or combined with isch2emia for one hour only, would produce this picture. Bywaters and Popjakhave recently shown that ischgemia of rabbit limbs due to tight binding if maintained for one hour produces only slight changes. If it is maintained for three hours or-more, irreversible muscle necrosis leads to limb swelling and hsemoconcentration, but to no permanent renal damage, judged by urea. and creatinine output or by histological criteria. A rise in blood-urea was obtained, due largely it was thought to increased katabolism, since the urea output was greater than in the control period. It is hard to compare these two sets of results, since in the rabbit experiments the criteria were rather more clinical "-than in the dog experiments. gross-more The dogs were killed without recovery from anesthesia ; -
’
"
5. Hunter, D. and Aub, J. C. Quart. J. Med. 1926, 20, 123. 6. Eggleton, M. G., Richardson, K. C., Schild, H. O. and Winton, F. R. Quart. J. exp. Physiol. 1943, 32, 89. 7. Bywaters, E. G. L. and Popjak, G. Surg. Gynec. Obstet. 1942, 75, 612.
ABSORPTION
AND
LEAD
POISONING
BEFORE the war there were more than 1500 workers in the lead industries of this country, and 150,000 painters. Today there are probably many more, and it is important that they should be safeguarded against poisoning. Absorption and poisoning are not synonymous, for many workers absorb a considerable amount of lead without developing symptoms. In the early stages the commonest symptoms are weakness, loss of weight, constipation and colic, and the most useful sign is the contrast between apparent muscular development and actual physical power. In the absence of later signs such as wrist drop, blue line on the gums and stippling of the red cells, the diagnosis of poisoning is a matter of clinical judgment not subject to proof. Buxellstates that the threshold limit for long exposure to lead and its compounds in the air is 1-5 mg. of lead per 10 cubic metres of air ; and work by Dreesen2 in 13 storage-battery plants east of the Mississippi River confirms this. He showed that among 776 workmen albuminuria and symptoms of early plumbism were most common in those exposed to the highest atmospheric lead concentration. Generally speaking, the urinary and blood lead estimations, reticulocyte, stipple-cell and polychromatophilia values also varied with the atmospheric lead concentrations. Employees who had an average lead exposure of more than 3 mg. per 10 cm. were smelters, pasters, oxide mixers, group assemblers, plate driers, finishers, and repairers. The prevalence of arterial hypertension among these employees was not significantly different from that observed in other industrial workers. Cholak and Bambach 3 found that in 1052 normal persons with no occupational lead hazard the mean lead concentrations were 0-030 mg. per 100 g. of blood, 0-027 mg. per litre of urine and 0.28 mg. per 24 hours" sample of faeces. Exposure to lead in industry raises these values, and the corresponding figures for 86 men engaged in making white lead were 0-086, 0.241 and 3-76. Data from representative groups of workmen may therefore be used to find out the character of exposure in a plant, to measure the uniformity and efficacy of the means employed to control the exposure and to establish whether it is uniform in severity ; and this exposure may be correlated with the atmospheric lead concentration. Working with Kehoe and others, the same observers 4 have shown that, excretion is much slower than accumulation, and that risk of poisoning can be reduced by alternating a period of exposure with a longer period of non-exposure. More absorbed lead is excreted in the urine than in the faeces, and since adequate urinary excretion depends on adequate intake of fluid, a supply of palatable water is important in an industrial plant. Constipation, since it is said to increase the absorption of lead from the gut, should also be avoided. Between 1900 and 1933 the mortality-rate from lead poisoning in the United States fell from 3-1 per million to 0-7, thanks mainly to improved methods of control and good personal.hygiene. The estimations, now 1. Buxell, J. J. industr. Hyg. 1943, 25, 35. 2. Dreesen, W. C. Ibid, p. 60. 3. Cholak, J. and Bambach, K. Ibid, p. 47. 4. Kehoe, R. A. Ibid ; Cholak, J., Hubbard, D. M., and McNary, R. R. Ibid, p. 71.
Bambach, K.
used in conjunction with stipple-cell counts, mark another advance in the control of this hazard; and there is good reason to hope that the condition will soon be obsolete and curative treatment no lounger necessary. Hunter and Aub5 showed that repeated injections of parathyroid extract in 6 patients with chronic lead poisoning rapidly and effectively mobilised some of the stored lead from the bones, and they confirmed a striking parallelism between the storage and excretion of lead and calcium. Kehoe and his colleagues,44 judging from one case examined over short periods, doubt whether elimination of lead from the body can be much accelerated by artificial means ; but this opinion is not acceptable without much more evidence.
suggested,
RENAL FUNCTION AFTER CRUSHING INJURY IN Britain at present opportunities for clinical investigation of crush syndrome are fortunately rare, but experimental work may shed some light on the mechanism of the renal injury or perhaps suggest methods of investigating such cases in man. In an ingenious series of experiments,6 a group of workers at University College have analysed in detail the depression of renal function they were able to produce in the anaesthetised animal-by crushing and hammering the tightly bound limb and then keeping it bloodless for 5 hours. Their main criterion was creatinine clearance, which was found to fall considerablv within a few minutes of release of the compressing tubing. This fall was followed by a period of anuria and low blood-pressure ; if urinary flow was then stimulated and blood-pressure raised by intravenous fluids of various kinds, the creatinine clearance rose, but only to half normal. At the same time the urine became acid and contained pigment and casts. The mechanism
of this damage was investigated by partial obstruction of the ureter on one side. This procedure,. by cutting down urine now, might be expected to concentrate any filtered toxin in the tubules ; but in four experiments there was no significantly increased damage. In the fifth experiment the measure even seemed to protect the kidney, for the creatinine clearance was higher after the obstruction was removed than on the control side. The damage was not due to anuria since it was still produced when diuretics maintained a flow throughout : it was not due to low arterial tension, since after histamine injection (with resultant hypotension and anuria), there was no such damage. The kidneys showed no ’structural lesion in any way comparable to the changes in man ; even the mitochondria were intact except in one animal which developed irreversible anuria. In particular, there was no histological evidence for blockage ; nor were the kidneys tense as they should have been if either blockage or poisoning of tubular epithelium alone had been responsible. It would be interesting to know if the hammering, either alone or combined with isch2emia for one hour only, would produce this picture. Bywaters and Popjakhave recently shown that ischgemia of rabbit limbs due to tight binding if maintained for one hour produces only slight changes. If it is maintained for three hours or-more, irreversible muscle necrosis leads to limb swelling and hsemoconcentration, but to no permanent renal damage, judged by urea. and creatinine output or by histological criteria. A rise in blood-urea was obtained, due largely it was thought to increased katabolism, since the urea output was greater than in the control period. It is hard to compare these two sets of results, since in the rabbit experiments the criteria were rather more clinical "-than in the dog experiments. gross-more The dogs were killed without recovery from anesthesia ; -
’
"
5. Hunter, D. and Aub, J. C. Quart. J. Med. 1926, 20, 123. 6. Eggleton, M. G., Richardson, K. C., Schild, H. O. and Winton, F. R. Quart. J. exp. Physiol. 1943, 32, 89. 7. Bywaters, E. G. L. and Popjak, G. Surg. Gynec. Obstet. 1942, 75, 612.