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MAGNESIUM IN HEART MUSCLE
644 SOMATOSTATIN AND DIABETIC KETOACIDOSIS
SIR,-In their first experiment Professor Lundbaek and his colleagues (Jan. 31, p. 215) infused somatostatin into 5 insulin-dependent diabetics for 4 h, 60-72 h after insulin withdrawal, during a period of progressively increasing ketosis. The ketone-body concentration rose in all patients during the 60 min control period. When somatostatin was added, the ketone-body concentration fell in 4 patients and increased further in the other. These results must be
interpreted cautiously. First,
conclusions about the effect of somatostatin infusion on ketosis without having performed appropriate control studies, since the ketone-body levels were still rising during the control period. Secondly, the statement that "ketone-body production was unaffected by changes in plasma-glucagon in patients with established ketoacidosis" cannot be supported since ketone-body production was not measured. Ketone-body production from blood-ketone concentration cannot be measured during an unsteady state since ketone-body uptake might be affected as well as production. This is particularly true for diabetic ketoacidosis where there is little correlation between hepatic ketone production rates and peripheral blood-ketone concentration.’ There may have been a marked suppression of ketone-body production during somatostatin infusion and the relatively slow fall in the blood-ketone levels may merely have reflected a low clearance-rate. The clearance of ketone-bodies is decreased during insulin deficiency2 and increased in response to insulin,3which might explain the faster fall of ketone concentrations in the patients during the second experiment. There was probably a distinct suppression of ketone-body production by somatostatin with only slight changes in blood-ketone concentrations. As noted, Gerich et al. have suggested that suppression of endogenous glucagon may cause the inhibiting effect of somatostatin on the development of diabetic ketosis. We have demonstrated that basal levels of glucagon are required for the accelerated hepatic ketogenesis observed during acute insulin deficiency in dogs.5 The data presented by Professor Lundbaek and his colleagues show that, as soon as there is sufficient insulin available, acute suppression of glucagon and growth-hormone has little effect on the correction of diabetic ketoacidosis. This emphasises the importance of early and adequate treatment with insulin.
Diabetes-Endocrinology Center, Vanderbilt University, ULRICH KELLER
PROPHYLAXIS OF BACTERIAL ENDOCARDITIS
SIR,—Iread with complete approval your editorial (March p. 519) which accords with my own conclusions arrived at after several years of study. My paper on this subject (referred to elsewhere6) has long been delayed largely due to editorial objection to its content. It is, therefore, gratifying to see that you conclude, as I have, that the proof is lacking and always
6,
will be for the relationship of infective endocarditis to dental work and for the efficiency of prophylaxis. Nevertheless, prophylaxis must continue to be offered. This should be as harmless as possible and as effective as possible. The importance of the experimental model gives the strongest support we have that this is good practice and gives us the best possible guidance to effective regimens. The antibiotic should not be given for long before dental extractions in case resistant 1. 2. 3. 4.
empty stomach one hour before dental treatment. Addenbrooke’s Hospital,
Owen, O. E., Reichard, G. A., Jr. Israel J. med. Sci. 1975, 11, 560. Ruderman, N. B., Goodman, M. N. Am. J. Physiol. 1974, 226, 136. Balasse, E. O., Havel, E. O. J. clin. Invest. 1971, 50, 801. Gerich, J. E., Lorenzi, M., Bier, D. M., Schneider, V., Tsalikian, E., Karam, O. H., Forsham, P. H. New Engl. J. Med. 1975, 292, 985. 5. Keller, U., Liljenquist, J. E., Chiasson, J. L., Cherrington, A. D. Crofford, O. B. Clin. Res. 1976, 24, 52A. 6. Fleming, H. A. Br. med. J. 1975, iii, 541.
H. A. FLEMING
Cambridge CB2 2QQ
MAGNESIUM IN HEART MUSCLE
it is im-
possible to draw definite
Nashville, Tennessee 37232, U.S.A.
organisms emerge. I recommend that the initial dose of phenoxymethylpenicillin should be given by mouth on an
SIR,—Dr Chipperfield and her colleagues (Jan. 17, p. 121) found residents of Burnley, a soft-water town, to have a mean myocardial magnesium of approximately 216 µg/g wet weight, This was close to the figure of 207 µg/g found among residents of soft-water towns in Ontario.’ However in Hull, a hardwater town, the mean myocardial magnesium was only 17S p.g/g (19% below the Burnley figure), a very different finding to that in Ontario, where the mean concentration was 8% higher (222 µg/g) among residents of hard-water towns. These workers’ suspicion that the unexpectedly low magnesium concentration in Hull was not the result of geographical variation but was due to procedural differences was strengthened by their finding that the myocardial potassium concentration was also much less in Hull than in Burnley; however, although they were unable to identify any procedural (ffferences, we think it premature to assume that such differences did not exist. We would welcome information on the interval between death and necropsy in each town, and the conditions under which the bodies were stored. Could it be that the differences in the apparent deficiencies of potassium (-37%), magnesium (-19%), and zinc (-9%) in the Hull samples are largely a reflection of the rates at which these elements leak out of the myocardial cells after death? Which part of which ventricle was sampled in each town, were any other elements measured, and is there any obvious explanation for the much highe! mean myocardial magnesium (205 µg/g) found in Hull in a previous study?2 We would also be grateful for information or the concentration of magnesium and other elements in the tw( water supplies, since although magnesium and hardness all usually well correlated, it does not necessarily follow that tht hardest water has the highest magnesium content. By relying on data from only two sources in order to characterise soft and hard water areas in general the authors havi considerably increased the risk of confounding due to other locally variable factors. We therefore hope that samples fron some other towns will be examined before these results an accepted as being typical of myocardial electrolytes in soft an( hard water areas of England. May we also suggest that the number of possible confounding variables be reduced by giving results in terms of dry tissue weight (thus avoiding variation due to tissue oedema), and by restricting comparisons to! single type of death, since we found that persons who had beet chronically ill tended to have lower myocardial magnesiun concentrations than persons who died suddenly from acciden or suicide.3 Department of Preventive Medicine Biostatistics, University of Toronto,
and
Canada
T. W. ANDERSON
Bureau of Epidemiology Health and Welfare, Ottawa
L. C. NERI
Department of Preventive Medicine and Biostatistics, University of Toronto Health Protection Branch, Health and Welfare, Ottawa National Research Council, Ottawa
1.
D. HEWITT
G. SCHREIBER J. R. MARIER
Anderson, T. W., Hewitt, D., Neri, L. C., Schreiber, G., Talbot, F. Lancet , 1973, ii, 1390. 2. Chipperfield, B., Chipperfield, J. R. ibid. 1973, ii, 293. 3. Anderson, T. W., Neri, L. C., Schreiber, G., Talbot, F., Zdrojewski, A. Can. med. Ass. J. 1975, 113, 199.
SIR,-In their first experiment Professor Lundbaek and his colleagues (Jan. 31, p. 215) infused somatostatin into 5 insulin-dependent diabetics for 4 h, 60-72 h after insulin withdrawal, during a period of progressively increasing ketosis. The ketone-body concentration rose in all patients during the 60 min control period. When somatostatin was added, the ketone-body concentration fell in 4 patients and increased further in the other. These results must be
interpreted cautiously. First,
conclusions about the effect of somatostatin infusion on ketosis without having performed appropriate control studies, since the ketone-body levels were still rising during the control period. Secondly, the statement that "ketone-body production was unaffected by changes in plasma-glucagon in patients with established ketoacidosis" cannot be supported since ketone-body production was not measured. Ketone-body production from blood-ketone concentration cannot be measured during an unsteady state since ketone-body uptake might be affected as well as production. This is particularly true for diabetic ketoacidosis where there is little correlation between hepatic ketone production rates and peripheral blood-ketone concentration.’ There may have been a marked suppression of ketone-body production during somatostatin infusion and the relatively slow fall in the blood-ketone levels may merely have reflected a low clearance-rate. The clearance of ketone-bodies is decreased during insulin deficiency2 and increased in response to insulin,3which might explain the faster fall of ketone concentrations in the patients during the second experiment. There was probably a distinct suppression of ketone-body production by somatostatin with only slight changes in blood-ketone concentrations. As noted, Gerich et al. have suggested that suppression of endogenous glucagon may cause the inhibiting effect of somatostatin on the development of diabetic ketosis. We have demonstrated that basal levels of glucagon are required for the accelerated hepatic ketogenesis observed during acute insulin deficiency in dogs.5 The data presented by Professor Lundbaek and his colleagues show that, as soon as there is sufficient insulin available, acute suppression of glucagon and growth-hormone has little effect on the correction of diabetic ketoacidosis. This emphasises the importance of early and adequate treatment with insulin.
Diabetes-Endocrinology Center, Vanderbilt University, ULRICH KELLER
PROPHYLAXIS OF BACTERIAL ENDOCARDITIS
SIR,—Iread with complete approval your editorial (March p. 519) which accords with my own conclusions arrived at after several years of study. My paper on this subject (referred to elsewhere6) has long been delayed largely due to editorial objection to its content. It is, therefore, gratifying to see that you conclude, as I have, that the proof is lacking and always
6,
will be for the relationship of infective endocarditis to dental work and for the efficiency of prophylaxis. Nevertheless, prophylaxis must continue to be offered. This should be as harmless as possible and as effective as possible. The importance of the experimental model gives the strongest support we have that this is good practice and gives us the best possible guidance to effective regimens. The antibiotic should not be given for long before dental extractions in case resistant 1. 2. 3. 4.
empty stomach one hour before dental treatment. Addenbrooke’s Hospital,
Owen, O. E., Reichard, G. A., Jr. Israel J. med. Sci. 1975, 11, 560. Ruderman, N. B., Goodman, M. N. Am. J. Physiol. 1974, 226, 136. Balasse, E. O., Havel, E. O. J. clin. Invest. 1971, 50, 801. Gerich, J. E., Lorenzi, M., Bier, D. M., Schneider, V., Tsalikian, E., Karam, O. H., Forsham, P. H. New Engl. J. Med. 1975, 292, 985. 5. Keller, U., Liljenquist, J. E., Chiasson, J. L., Cherrington, A. D. Crofford, O. B. Clin. Res. 1976, 24, 52A. 6. Fleming, H. A. Br. med. J. 1975, iii, 541.
H. A. FLEMING
Cambridge CB2 2QQ
MAGNESIUM IN HEART MUSCLE
it is im-
possible to draw definite
Nashville, Tennessee 37232, U.S.A.
organisms emerge. I recommend that the initial dose of phenoxymethylpenicillin should be given by mouth on an
SIR,—Dr Chipperfield and her colleagues (Jan. 17, p. 121) found residents of Burnley, a soft-water town, to have a mean myocardial magnesium of approximately 216 µg/g wet weight, This was close to the figure of 207 µg/g found among residents of soft-water towns in Ontario.’ However in Hull, a hardwater town, the mean myocardial magnesium was only 17S p.g/g (19% below the Burnley figure), a very different finding to that in Ontario, where the mean concentration was 8% higher (222 µg/g) among residents of hard-water towns. These workers’ suspicion that the unexpectedly low magnesium concentration in Hull was not the result of geographical variation but was due to procedural differences was strengthened by their finding that the myocardial potassium concentration was also much less in Hull than in Burnley; however, although they were unable to identify any procedural (ffferences, we think it premature to assume that such differences did not exist. We would welcome information on the interval between death and necropsy in each town, and the conditions under which the bodies were stored. Could it be that the differences in the apparent deficiencies of potassium (-37%), magnesium (-19%), and zinc (-9%) in the Hull samples are largely a reflection of the rates at which these elements leak out of the myocardial cells after death? Which part of which ventricle was sampled in each town, were any other elements measured, and is there any obvious explanation for the much highe! mean myocardial magnesium (205 µg/g) found in Hull in a previous study?2 We would also be grateful for information or the concentration of magnesium and other elements in the tw( water supplies, since although magnesium and hardness all usually well correlated, it does not necessarily follow that tht hardest water has the highest magnesium content. By relying on data from only two sources in order to characterise soft and hard water areas in general the authors havi considerably increased the risk of confounding due to other locally variable factors. We therefore hope that samples fron some other towns will be examined before these results an accepted as being typical of myocardial electrolytes in soft an( hard water areas of England. May we also suggest that the number of possible confounding variables be reduced by giving results in terms of dry tissue weight (thus avoiding variation due to tissue oedema), and by restricting comparisons to! single type of death, since we found that persons who had beet chronically ill tended to have lower myocardial magnesiun concentrations than persons who died suddenly from acciden or suicide.3 Department of Preventive Medicine Biostatistics, University of Toronto,
and
Canada
T. W. ANDERSON
Bureau of Epidemiology Health and Welfare, Ottawa
L. C. NERI
Department of Preventive Medicine and Biostatistics, University of Toronto Health Protection Branch, Health and Welfare, Ottawa National Research Council, Ottawa
1.
D. HEWITT
G. SCHREIBER J. R. MARIER
Anderson, T. W., Hewitt, D., Neri, L. C., Schreiber, G., Talbot, F. Lancet , 1973, ii, 1390. 2. Chipperfield, B., Chipperfield, J. R. ibid. 1973, ii, 293. 3. Anderson, T. W., Neri, L. C., Schreiber, G., Talbot, F., Zdrojewski, A. Can. med. Ass. J. 1975, 113, 199.