888
antibodies following steroid therapy was seen. Measurement of the density of antibody binding on spermatozoa is better than the usual estimation of the percentage of antibody-positive spermatozoa :2 the latter technique is dependent on the method of collection of spermatozoa for analysis-eg, in the usual "swim-up" technique the number of dead spermatozoa included in the sample is variable, and since dead spermatozoa take up antibody non-specifically the percentage of positive spermatozoa obtained depends on the proportion of dead spermatozoa in the sample. We estimated the proportion of dead spermatozoa in the ejaculate of 28 patients attending the infertility clinic. PI labelling showed that the mean percentage of dead spermatozoa in the ejaculate was 32%. Thus, measurement of the amount of antibody binding when combined with a simultaneous estimation of antibody-positive live cells should offer the most definitive answer in the evaluation of various treatments. The method we report is objective and precise, but provides an approximation of the number of antibody molecules per spermatozoa. If more accuracy is needed the standards themselves should be calibrated by isoparametric analysis.3
Departments of Anatomy and Clinical Chemistry, University of Kuopio, 70211 Kuopio, Finland 1.
MARITA RÄSÄNEN MARKKU SAARANEN ILKKA PENTTILÄ YASH PAL AGRAWAL
Hendry WF, Hughes L, Scammell G, Pryor JP, Hargreave TB. Comparison of prednisolone and placebo in subfertile men with antibodies to spermatozoa Lancet 1990; 335: 85-88
2. Haas GG, D’Cruz JD, DeBault LE. Assessment by fluorescence-activated cell sorting of whether sperm-associated immunoglobulin (Ig)G and IgA occur on the same sperm population. Fertil Steril 1990; 54: 127-32. 3. Chatelier RC. Ashcroft RG. Calibration of flow cytometric fluorescence standards using the isoparametnc analysis of ligand binding. Cytometry 1987; 8: 632-36.
Aluminium deposition in bone after contamination of drinking water supply SIR,-Dr Eastwood and colleagues’ report (Aug 25, p 462) of aluminium deposition in bone after contamination of the drinking water supply demonstrates two important points: they show that even patients with normal renal function can accumulate aluminium and that some people may be unexpectedly at risk of aluminium toxicity. Although both the quantity and form of aluminium ingested were atypical, the results emphasise the need to consider more carefully long-term exposure to the level of aluminium in the diet. Aluminium has only this century been released from ubiquitous but stable aluminosilicate minerals, and so now is present in our diet as a potential toxin. The gastrointestinal absorption of aluminium is usually poor, and why this is so and how an increased load is absorbed are not understood. The concomitant ingestion of acid and aluminium would not, as suggested by Eastwood et al, promote aluminium absorption. The increase in systemic aluminium when given with citric acid results from the formation of a better absorbed aluminium citrate complex, and is not merely a function of acid. There is no evidence that the uptake of aluminium involves to any great extent the ionised form, as wrongly suggested in the Lowermoor Incident Health Advisory Group report.! The stomach is probably a poor site for aluminium absorption. We have been investigating the fate of aluminium in the lumen of the small bowel and find that precipitation, which is often said to occur in this neutral environment, does not happen. Formation of an insoluble aluminium hydroxide or phosphate is often given as a reason for the poor absorption of aluminium, but at 20 mg/1 aluminium, precipitation or even interaction between aluminium and solids is negligible, except when there is an especially high affinity between two phases—eg, when solid-phase silicon is present. Even then, adsorption of aluminium to such silicon is slow compared with small intestinal transit. The reason for the increased metastability (ie, non-precipitation) of aluminium during intestinal transit is unclear, but endogenous ligands may be responsible. We have demonstrated that these ligands are present in, for example, bile and pancreatic juice. Our work also suggests that there are factors in the mucosa or mucus that limit intestinal aluminium absorption.
Thus the fate of aluminium in the gastrointestinal tract is unknown and difficult to predict. There is, as shown by Eastwood et al, increasing evidence that even some healthy individuals may not excrete all the absorbed aluminium which, in this study, was demonstrable in bone. The long-term effects of absorption and distribution of dietary aluminium should therefore be elucidated. Gastrointestinal Laboratory,
Rayne Institute,
J. J. POWELL
St Thomas’ Hospital, London SE1 7EH, UK
R. P. H. THOMPSON
1 Water Pollution at Lowermoor, North Cornwall. Report of the Lowermoor Incident Health Advisory Group (Chairman. Professor Dame Barbara Clayton), July, 1989
Sleep apnoea and myocardial infarction SiR,—Dr Hung and his colleagues (Aug 4, p 261) provide useful and important additional information about the potential impact of sleep disordered breathing. However, the hypothesis that ischaemic heart disease or myocardial infarction causes sleep apnoea is not as implausible as Hung et al would have us believe. Contrary to their statement there is indeed evidence that cardiovascular drugs, in particular antihypertensive agents, might worsen or even precipitate sleep apnoea. a-methyldopa has been shown to reduce alae nasi activity selectively.’ In doing so, resistance to airflow through the upper airway is increased, leading to a greater luminal suction pressure and possible collapse of the pharyngeal airway. In addition there are reports of deterioration of sleep apnoea during treatment with propranolol,2 and a comparison of 175 hypertensive men and 100 normotensive men showed that the group with raised blood pressure, persistent even with antihypertensive drug therapy, had the most sleep apnoea.3 Information about the drugs being taken at the time of infarction or of investigation would be very
important. To conclude, as did Hung et al, that sleep apnoea can precipitate myocardial ischaemia is plausible, but to ignore the possible aetiological role of concomitant drugs in its development is to miss a potentially very simple and useful therapeutic intervention. West Los Angeles VA Medical Center, Los Angeles California 90073, USA, and Sleep Disorders Center, UCLA
ADRIAN WILLIAMS
KC, Weiss JW. Wemberger SE Alpha-methyldopa selectivity reduces alae nasi activity. Clin Sci 1988; 74: 547-51 2. Boudoulas H, Schmidt H, Gelens P, Clark RW, Lewis RP. Case reports on deterioration of sleep apnea during therapy with propranolol: preliminary studies Res Commun Chem Pathol Pharmacol 1983; 39: 3-10 3. Hirschkowitz M, Karacan I, Gurakar A, Williams RL. Hypertension, erectile dysfunction and occult sleep apnea. Sleep 1989; 12: 223-32. 1. Lahive
Cardiac
biopsy in myocarditis
SIR,7-Your Aug 4 editorial on cardiac biopsy in myocarditis dealt with only one aspect of the diagnostic dilemma-the false negatives. The false positives are equally important in diagnosis of myocarditis. Whereas sampling errors account for most falsenegative diagnoses, false-positive diagnoses may result from misinterpretation of non-inflammatory cells as lymphocytes and from clinical bias.1 At least 30 studies have used cardiac biopsy to determine the frequency of myocarditis in patients with unexplained heart failure or dilated cardiomyopathy.2 The fact that frequencies varied widely, from 0 to 67 %, has been used to suggest that cardiac biopsy has no practical use in evaluation of myocarditisThus, Edwards’ emphasises three guidelines for evaluation of myocarditis by cardiac biopsy. Firstly, like all clinical tests, cardiac biopsy has certain limitations, of which sampling error is the most important. Secondly, within the myocardial interstitium, a small number of itinerant leucocytes are to be expected, and some non-inflammatory cells (when cut in cross-section) resemble lymphocytes and macrophages. Thirdly, only positive findings
are
regarded
as
antibodies following steroid therapy was seen. Measurement of the density of antibody binding on spermatozoa is better than the usual estimation of the percentage of antibody-positive spermatozoa :2 the latter technique is dependent on the method of collection of spermatozoa for analysis-eg, in the usual "swim-up" technique the number of dead spermatozoa included in the sample is variable, and since dead spermatozoa take up antibody non-specifically the percentage of positive spermatozoa obtained depends on the proportion of dead spermatozoa in the sample. We estimated the proportion of dead spermatozoa in the ejaculate of 28 patients attending the infertility clinic. PI labelling showed that the mean percentage of dead spermatozoa in the ejaculate was 32%. Thus, measurement of the amount of antibody binding when combined with a simultaneous estimation of antibody-positive live cells should offer the most definitive answer in the evaluation of various treatments. The method we report is objective and precise, but provides an approximation of the number of antibody molecules per spermatozoa. If more accuracy is needed the standards themselves should be calibrated by isoparametric analysis.3
Departments of Anatomy and Clinical Chemistry, University of Kuopio, 70211 Kuopio, Finland 1.
MARITA RÄSÄNEN MARKKU SAARANEN ILKKA PENTTILÄ YASH PAL AGRAWAL
Hendry WF, Hughes L, Scammell G, Pryor JP, Hargreave TB. Comparison of prednisolone and placebo in subfertile men with antibodies to spermatozoa Lancet 1990; 335: 85-88
2. Haas GG, D’Cruz JD, DeBault LE. Assessment by fluorescence-activated cell sorting of whether sperm-associated immunoglobulin (Ig)G and IgA occur on the same sperm population. Fertil Steril 1990; 54: 127-32. 3. Chatelier RC. Ashcroft RG. Calibration of flow cytometric fluorescence standards using the isoparametnc analysis of ligand binding. Cytometry 1987; 8: 632-36.
Aluminium deposition in bone after contamination of drinking water supply SIR,-Dr Eastwood and colleagues’ report (Aug 25, p 462) of aluminium deposition in bone after contamination of the drinking water supply demonstrates two important points: they show that even patients with normal renal function can accumulate aluminium and that some people may be unexpectedly at risk of aluminium toxicity. Although both the quantity and form of aluminium ingested were atypical, the results emphasise the need to consider more carefully long-term exposure to the level of aluminium in the diet. Aluminium has only this century been released from ubiquitous but stable aluminosilicate minerals, and so now is present in our diet as a potential toxin. The gastrointestinal absorption of aluminium is usually poor, and why this is so and how an increased load is absorbed are not understood. The concomitant ingestion of acid and aluminium would not, as suggested by Eastwood et al, promote aluminium absorption. The increase in systemic aluminium when given with citric acid results from the formation of a better absorbed aluminium citrate complex, and is not merely a function of acid. There is no evidence that the uptake of aluminium involves to any great extent the ionised form, as wrongly suggested in the Lowermoor Incident Health Advisory Group report.! The stomach is probably a poor site for aluminium absorption. We have been investigating the fate of aluminium in the lumen of the small bowel and find that precipitation, which is often said to occur in this neutral environment, does not happen. Formation of an insoluble aluminium hydroxide or phosphate is often given as a reason for the poor absorption of aluminium, but at 20 mg/1 aluminium, precipitation or even interaction between aluminium and solids is negligible, except when there is an especially high affinity between two phases—eg, when solid-phase silicon is present. Even then, adsorption of aluminium to such silicon is slow compared with small intestinal transit. The reason for the increased metastability (ie, non-precipitation) of aluminium during intestinal transit is unclear, but endogenous ligands may be responsible. We have demonstrated that these ligands are present in, for example, bile and pancreatic juice. Our work also suggests that there are factors in the mucosa or mucus that limit intestinal aluminium absorption.
Thus the fate of aluminium in the gastrointestinal tract is unknown and difficult to predict. There is, as shown by Eastwood et al, increasing evidence that even some healthy individuals may not excrete all the absorbed aluminium which, in this study, was demonstrable in bone. The long-term effects of absorption and distribution of dietary aluminium should therefore be elucidated. Gastrointestinal Laboratory,
Rayne Institute,
J. J. POWELL
St Thomas’ Hospital, London SE1 7EH, UK
R. P. H. THOMPSON
1 Water Pollution at Lowermoor, North Cornwall. Report of the Lowermoor Incident Health Advisory Group (Chairman. Professor Dame Barbara Clayton), July, 1989
Sleep apnoea and myocardial infarction SiR,—Dr Hung and his colleagues (Aug 4, p 261) provide useful and important additional information about the potential impact of sleep disordered breathing. However, the hypothesis that ischaemic heart disease or myocardial infarction causes sleep apnoea is not as implausible as Hung et al would have us believe. Contrary to their statement there is indeed evidence that cardiovascular drugs, in particular antihypertensive agents, might worsen or even precipitate sleep apnoea. a-methyldopa has been shown to reduce alae nasi activity selectively.’ In doing so, resistance to airflow through the upper airway is increased, leading to a greater luminal suction pressure and possible collapse of the pharyngeal airway. In addition there are reports of deterioration of sleep apnoea during treatment with propranolol,2 and a comparison of 175 hypertensive men and 100 normotensive men showed that the group with raised blood pressure, persistent even with antihypertensive drug therapy, had the most sleep apnoea.3 Information about the drugs being taken at the time of infarction or of investigation would be very
important. To conclude, as did Hung et al, that sleep apnoea can precipitate myocardial ischaemia is plausible, but to ignore the possible aetiological role of concomitant drugs in its development is to miss a potentially very simple and useful therapeutic intervention. West Los Angeles VA Medical Center, Los Angeles California 90073, USA, and Sleep Disorders Center, UCLA
ADRIAN WILLIAMS
KC, Weiss JW. Wemberger SE Alpha-methyldopa selectivity reduces alae nasi activity. Clin Sci 1988; 74: 547-51 2. Boudoulas H, Schmidt H, Gelens P, Clark RW, Lewis RP. Case reports on deterioration of sleep apnea during therapy with propranolol: preliminary studies Res Commun Chem Pathol Pharmacol 1983; 39: 3-10 3. Hirschkowitz M, Karacan I, Gurakar A, Williams RL. Hypertension, erectile dysfunction and occult sleep apnea. Sleep 1989; 12: 223-32. 1. Lahive
Cardiac
biopsy in myocarditis
SIR,7-Your Aug 4 editorial on cardiac biopsy in myocarditis dealt with only one aspect of the diagnostic dilemma-the false negatives. The false positives are equally important in diagnosis of myocarditis. Whereas sampling errors account for most falsenegative diagnoses, false-positive diagnoses may result from misinterpretation of non-inflammatory cells as lymphocytes and from clinical bias.1 At least 30 studies have used cardiac biopsy to determine the frequency of myocarditis in patients with unexplained heart failure or dilated cardiomyopathy.2 The fact that frequencies varied widely, from 0 to 67 %, has been used to suggest that cardiac biopsy has no practical use in evaluation of myocarditisThus, Edwards’ emphasises three guidelines for evaluation of myocarditis by cardiac biopsy. Firstly, like all clinical tests, cardiac biopsy has certain limitations, of which sampling error is the most important. Secondly, within the myocardial interstitium, a small number of itinerant leucocytes are to be expected, and some non-inflammatory cells (when cut in cross-section) resemble lymphocytes and macrophages. Thirdly, only positive findings
are
regarded
as
