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ALUMINIUM TOXICITY
47 per 100 ml.). A large amount of tyrosyl compounds was found in the urine. Kidney and liver function tests were normal.
Radiological examination
was
unremarkable except for
a
peculiar streaked appearance of both femora (see figure). The patient was placed on a diet with limited phenylalanine and tyrosine.22 A nearly normal blood-tyrosine level was maintained for over a year, with the unexpected result of complete remission of the skin lesions for the first time in her life. Radiographs of the femora after a year of dietary remained unchanged. A skeletal examination of patient’s mother and grandmother showed no abnormal findings. This is a rare case of tyrosinosis (tyrosinaemia and tyrosyluria) without hepatorenal failure. We have been treatment
the
unable to find any reports of the peculiar streakiness of the femora, and we are unable to explain this finding, which may possibly be unrelated to the biochemical lesions. Alvin Buckwold Centre, Department of Pediatrics, and
Department of Radiology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
WITOLD A. ZALESKI C. STUART HOUSTON ALAN HILL.
ALUMINIUM TOXICITY
SIR,-May we be permitted to answer some of the relevant points in the letters from Dr. Thurston and Dr. Swales and from Dr. Sherrard (June 3, p. 1241) ? 1. The route and salt used in aluminium administration are, as we stated, not directly applicable to man; the point of our article was to show that with blood-levels in rats similar to those found in man with renal failure taking aluminium salts, toxicity was demonstrated. It is dimcult to extrapolate from rat to man, but Dr. Sherrard might find it worth recalling that in mice in which cigarette tar was painted on the skin, neoplasms developed, and this was regarded as evidence implicating cigarette smoking in the setiology of carcinoma of the lung in man. 2. Dr. Thurston is correct: the decimal point was inadvertently moved; the mean aluminium level in nonnephrectomised rat femur was 182.7 mg. per kg. dryweight (range 23-1-266 mg. per kg.). 3. Plasma to determine aluminium levels can be readily obtained in man, and if aluminium is given parenterally or the rats are starved overnight before blood is removed, then we can compare plasma-aluminium levels in man and rat. Levels of other toxic agents are determined on plasma samples routinely in the assessment of intoxication. 4. The risk in the use of aluminium in regular dialysis patients is probably slight, because aluminium is dialysed out. In non-dialysed patients with advanced chronic renal failure, the situation is different, however, and aluminium 3 may build up to high plasma levels.3 5. Dr. Sherrard has an alternative to aluminium hydroxide to control plasma-phosphate levels. Giovannetti has recently introduced a palatable coated anion-exchange resin in the acetate form which binds phosphate and corrects acidosis in ura:mia. It does not liberate cations such as aluminium. The anion-exchange resin is marketed by Farmitalia of Milan. We hope that Dr. Sherrard will find it helpful in his patients in controlling their phosphate levels. Moreover, Fearing’s investigation of aluminiumhydroxide ingestion in dialysis patients can be recommended for study by all nephrologists.4 She points out that all 26 dialysis patients investigated had gastrointestinal symptoms as a result of aluminium-hydroxide ingestion, and con2.
Hill, A., Nordin, P. M., Zaleski, W. A. J. Am. Diet. Ass. 1970,
56, 308. Berlyne, G. M., Ben-Ari, J., Pest, D., Weinberger, J., Stern, M., Gillmore, G. R., Levine, R. Lancet, 1970, ii, 494. 4. Fearing, M. Vinculum, 1972, 5, 4. 3.
sequently only 8 patients hydroxide.
out
of 26 took all the prescribed
aluminium
Negev Central Hospital, P.O. Box 151, Beer-Sheba, Israel.
G. M. BERLYNE R. YAGIL.
PRACTOLOL AND ISOPRENALINE IN STATUS ASTHMATICUS SIR,-We wish to report the successful use of a combination of practolol and isoprenaline given intravenously in a case of status asthmaticus where other forms of therapy had failed. The patient was a man of 53 with a 15-year history of intermittent asthma whose exercise tolerance was normal between attacks. His last hospital admission was 5 years ago, and he had been treated since with intermittent courses of prednisolone and Franol’ (ephedrine, phenobarbitone, and theophylline). On April 23, 1972, he presented with a 24-hour history of severe dyspnoea and was treated initially with intravenous fluid replacement (8 litres in 24 hours), intravenous aminophylline 500 mg. 6-hourly, intravenous hydrocortisone 300 mg. 3-hourly, intramuscular ampicillin 500 mg. 6-hourly, oral salbutamol 2 mg. 6-hourly, and humidification of inspired air buyMistogen 143’ nebuliser. 3 hours after admission blood-gas tensions were recorded at Pao2 77 mm. Hg and PC02 58 mm. Hg. He showed no improvement and 44 hours later was exhausted, with Pao2 58 mm. Hg and Pco2 70 mm. Hg. He was intubated and ventilated on a Cape Waine machine (rate 17 per minute, tidal volume 700 ml., pressure 40 cm. water), initially under sedation with phenoperidine, later relaxed with pancuronium. Ventilator pressures remained high after 4 hours on intermittent positivepressure ventilation, and the patient was cyanosed with intense bronchospasm (tidal volume 700 ml., pressure 60 cm. water), necessitating manual ventilation with oxygen-halothane mixture 1-4% via a Boyle’s machine. At this time there was no clinical or radiological evidence of pneumothorax or gross collapse. Bronchial lavage1 with 1500 ml. physiological saline over 90 minutes produced only a few bronchial plugs but no reduction in ventilator pressures. At this point practolol 5 mg. was given intravenously followed by isoprenaline 5 mg., with immediate improvement in the patient’s condition and in compliance (tidal volume 1000 ml., pressure 25 cm. water). There was insignificant increase in cardiac rate, with flushing of the skin. The bronchodilator effect lasted for 3 hours, and the same regimen was repeated four times. 12 hours after the initial dose the Pao2 was 82 mm. Hg and PC02 43 mm. Hg. After 56 hours the patient was extubated, and the steroids were tailed off. He has since been discharged home. In this patient an immediate and striking improvement followed intravenous administration of isoprenaline and practolol. The use of aerosol inhalations of isoprenaline in the treatment of asthma is well established but is limited in severely ill patients by the fall in arterial oxygen tension due to its beta-1 action. Salbutamol has a greater beta-2 Streeton and Morgan2 action than beta-1 activity. obtained good results in a series of patients with refractory status asthmaticus by administering salbutamol solution via a Bird mark 8 ventilator nebuliser. In 1969 Palmer et a1.3 showed that the beta-1 effect of 1 mg. isoprenaline aerosol inhalation could be eliminated by pretreatment with practolol; the resultant bronchodilatation was not 1. 2. 3.
Williams, N. E., Crook, J. W. Lancet, 1968, i, 1081. Streeton, J. A., Morgan, E. B. Postgrad. med. J. 1971, 47, suppl. 125. Palmer, K. N. V., Legge, J. S., Hamilton, W. F. B., Diament, M. L. Lancet, 1969, ii, 1092.
Radiological examination
was
unremarkable except for
a
peculiar streaked appearance of both femora (see figure). The patient was placed on a diet with limited phenylalanine and tyrosine.22 A nearly normal blood-tyrosine level was maintained for over a year, with the unexpected result of complete remission of the skin lesions for the first time in her life. Radiographs of the femora after a year of dietary remained unchanged. A skeletal examination of patient’s mother and grandmother showed no abnormal findings. This is a rare case of tyrosinosis (tyrosinaemia and tyrosyluria) without hepatorenal failure. We have been treatment
the
unable to find any reports of the peculiar streakiness of the femora, and we are unable to explain this finding, which may possibly be unrelated to the biochemical lesions. Alvin Buckwold Centre, Department of Pediatrics, and
Department of Radiology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
WITOLD A. ZALESKI C. STUART HOUSTON ALAN HILL.
ALUMINIUM TOXICITY
SIR,-May we be permitted to answer some of the relevant points in the letters from Dr. Thurston and Dr. Swales and from Dr. Sherrard (June 3, p. 1241) ? 1. The route and salt used in aluminium administration are, as we stated, not directly applicable to man; the point of our article was to show that with blood-levels in rats similar to those found in man with renal failure taking aluminium salts, toxicity was demonstrated. It is dimcult to extrapolate from rat to man, but Dr. Sherrard might find it worth recalling that in mice in which cigarette tar was painted on the skin, neoplasms developed, and this was regarded as evidence implicating cigarette smoking in the setiology of carcinoma of the lung in man. 2. Dr. Thurston is correct: the decimal point was inadvertently moved; the mean aluminium level in nonnephrectomised rat femur was 182.7 mg. per kg. dryweight (range 23-1-266 mg. per kg.). 3. Plasma to determine aluminium levels can be readily obtained in man, and if aluminium is given parenterally or the rats are starved overnight before blood is removed, then we can compare plasma-aluminium levels in man and rat. Levels of other toxic agents are determined on plasma samples routinely in the assessment of intoxication. 4. The risk in the use of aluminium in regular dialysis patients is probably slight, because aluminium is dialysed out. In non-dialysed patients with advanced chronic renal failure, the situation is different, however, and aluminium 3 may build up to high plasma levels.3 5. Dr. Sherrard has an alternative to aluminium hydroxide to control plasma-phosphate levels. Giovannetti has recently introduced a palatable coated anion-exchange resin in the acetate form which binds phosphate and corrects acidosis in ura:mia. It does not liberate cations such as aluminium. The anion-exchange resin is marketed by Farmitalia of Milan. We hope that Dr. Sherrard will find it helpful in his patients in controlling their phosphate levels. Moreover, Fearing’s investigation of aluminiumhydroxide ingestion in dialysis patients can be recommended for study by all nephrologists.4 She points out that all 26 dialysis patients investigated had gastrointestinal symptoms as a result of aluminium-hydroxide ingestion, and con2.
Hill, A., Nordin, P. M., Zaleski, W. A. J. Am. Diet. Ass. 1970,
56, 308. Berlyne, G. M., Ben-Ari, J., Pest, D., Weinberger, J., Stern, M., Gillmore, G. R., Levine, R. Lancet, 1970, ii, 494. 4. Fearing, M. Vinculum, 1972, 5, 4. 3.
sequently only 8 patients hydroxide.
out
of 26 took all the prescribed
aluminium
Negev Central Hospital, P.O. Box 151, Beer-Sheba, Israel.
G. M. BERLYNE R. YAGIL.
PRACTOLOL AND ISOPRENALINE IN STATUS ASTHMATICUS SIR,-We wish to report the successful use of a combination of practolol and isoprenaline given intravenously in a case of status asthmaticus where other forms of therapy had failed. The patient was a man of 53 with a 15-year history of intermittent asthma whose exercise tolerance was normal between attacks. His last hospital admission was 5 years ago, and he had been treated since with intermittent courses of prednisolone and Franol’ (ephedrine, phenobarbitone, and theophylline). On April 23, 1972, he presented with a 24-hour history of severe dyspnoea and was treated initially with intravenous fluid replacement (8 litres in 24 hours), intravenous aminophylline 500 mg. 6-hourly, intravenous hydrocortisone 300 mg. 3-hourly, intramuscular ampicillin 500 mg. 6-hourly, oral salbutamol 2 mg. 6-hourly, and humidification of inspired air buyMistogen 143’ nebuliser. 3 hours after admission blood-gas tensions were recorded at Pao2 77 mm. Hg and PC02 58 mm. Hg. He showed no improvement and 44 hours later was exhausted, with Pao2 58 mm. Hg and Pco2 70 mm. Hg. He was intubated and ventilated on a Cape Waine machine (rate 17 per minute, tidal volume 700 ml., pressure 40 cm. water), initially under sedation with phenoperidine, later relaxed with pancuronium. Ventilator pressures remained high after 4 hours on intermittent positivepressure ventilation, and the patient was cyanosed with intense bronchospasm (tidal volume 700 ml., pressure 60 cm. water), necessitating manual ventilation with oxygen-halothane mixture 1-4% via a Boyle’s machine. At this time there was no clinical or radiological evidence of pneumothorax or gross collapse. Bronchial lavage1 with 1500 ml. physiological saline over 90 minutes produced only a few bronchial plugs but no reduction in ventilator pressures. At this point practolol 5 mg. was given intravenously followed by isoprenaline 5 mg., with immediate improvement in the patient’s condition and in compliance (tidal volume 1000 ml., pressure 25 cm. water). There was insignificant increase in cardiac rate, with flushing of the skin. The bronchodilator effect lasted for 3 hours, and the same regimen was repeated four times. 12 hours after the initial dose the Pao2 was 82 mm. Hg and PC02 43 mm. Hg. After 56 hours the patient was extubated, and the steroids were tailed off. He has since been discharged home. In this patient an immediate and striking improvement followed intravenous administration of isoprenaline and practolol. The use of aerosol inhalations of isoprenaline in the treatment of asthma is well established but is limited in severely ill patients by the fall in arterial oxygen tension due to its beta-1 action. Salbutamol has a greater beta-2 Streeton and Morgan2 action than beta-1 activity. obtained good results in a series of patients with refractory status asthmaticus by administering salbutamol solution via a Bird mark 8 ventilator nebuliser. In 1969 Palmer et a1.3 showed that the beta-1 effect of 1 mg. isoprenaline aerosol inhalation could be eliminated by pretreatment with practolol; the resultant bronchodilatation was not 1. 2. 3.
Williams, N. E., Crook, J. W. Lancet, 1968, i, 1081. Streeton, J. A., Morgan, E. B. Postgrad. med. J. 1971, 47, suppl. 125. Palmer, K. N. V., Legge, J. S., Hamilton, W. F. B., Diament, M. L. Lancet, 1969, ii, 1092.