1034
OBESITY, DIET,
AND TYPE-II
HYPERLIPIDÆMIA SIR,-Leelarthaepin et al.1 demonstrated a significant correlation between weight-reduction and lowering of plasma-cholesterol. It was perhaps unfortunate that they chose to discuss their results in terms of hyperlipidaemic types and ischaemic heart-disease. While the occurrence of premature ischaemic heartdisease in familial hyperlipidaemias such as homozygous type-IIa hyperlipoproteinaemia2 (better described as homozygous familial hypercholesterolaemia 3) is well
recognised, there is no evidence that lipoprotein estimation and typing provide a better correlation with ischaemic _heart-disease than
measurements
of cholesterol
and
triglycerides alone.4 Typing of hyperlipidaemias, as previously noted,5 represents an artificial compartmentalisation of data which cannot thus be categorised. This is indeed brought out by the observations of Leelarthaepin et al., who demonstrated a change from type-ii to type-iv hyperlipidaemia with weight-reduction. If typing has to be used at all, its use should be restricted to the familial disorders. Typing of the non-familial or exogenous disturbances in lipid metabolism merely compounds the confusion that already exists in this field. We suggest that the common varieties of non-familial hyperlipidaemias, which include hypercholesterolaemia, hypertriglyceridsemia, and variable combinations of both, should be termed idiopathic. The World Health Organisation classification 6 would thus read:
(1) Secondary hyperlipidaemias;
disorders associated with, and certain drugs
Alcohol e.g., diabetes, hypothyroidism, &c. may also be listed as secondary causes.
(2) Primary hyperlipidaemias, (a) genetic idiopathic.
or
familial, (b)
Idiopathic primary hyperlipidaemias are the variety seen commonly in people exposed to the western life style, with overnutrition, obesity, lack of exercise, and stress all acting as aetiological agents, and they are detected in most epidemiological surveys of ischaemic heart-disease. The term idiopathic is not meant to imply that a single homogenous entity is described; doubtless it will be discarded as further studies clarify the picture of the aetiology and pathogenesis of the hyperlipidasmias.
most
A. C. ASMAL W. P. LEARY.
BLOOD-CHOLESTEROL
SIR,—Professor Whyte’s attempt (April 19, a
p.
906)
to
clinical message from the Framingham study fundamental misunderstanding. He relates the
developing
coronary
J. C. BIGNALL.
DANTROLENE INEFFECTIVE IN MYOTONIC DYSTROPHY
SIR,—We should like to report a clinical trial of dantrolene sodium in a patient with myotonic dystrophy. A 50-year-old White male, as a young man had had difficulty with agility and fine hand movements. He worked as a cook in the Armed Forces and was able to function normally. He was admitted to the hospital for evaluation of slowly progressive abnormalities of gait and grip strength as well as anterior thigh pain. Examination revealed distal muscle wasting, frontal baldness, and percussion myotonia, which was confirmed by electromyographic examination. Quadriceps tenderness was also noted. There was no family history of muscle weakness, but both his father and paternal grandfather became bald early. The patient has no siblings. The quadriceps pain was thought to be secondary to repetitive muscle activity. Procainamide, phenytoin (’ Dilantin’), and quinidine were tried to no avail. Oral dantrolene sodium (100 mg. four times daily) was given for three weeks with no change in symptoms. There was no change in the myotonia either clinically or electromyographically. There was an increased number of potentials recorded from the opponens pollicis while he was exerting a 3-lb. force on a dynamometer.
deficit
CORONARY HEART-DISEASE AND
fails on risk of
The Surgery, Newport, Pembs. SA42 0TS.
Myotonia is probably due to a muscle-fibre membrane producing repetitive discharges. Although the exact nature of this defect is unknown the resting membrane potential is lower than normaland the membrane
Department of Clinical and
Experimental Pharmacology, Faculty of Medicine, University of Natal, Durban, South Africa.
extract a
benefit from wearing a wig. If he wishes to show that lowering the serum-cholesterol is beneficial then he must contrast the risk of C.H.D. between a group of men with a high cholesterol who have had it lowered and a group with a high cholesterol which is allowed to remain high. The epidemiologist may be interested to observe characteristics associated with a high risk, the clinician wants to know what evidence there is that altering the characteristic will improve the risk. Professor Whyte’s analysis is no help in answering that question. Apart from this logical lapse one cannot help but feel suspicious about his" numerical conclusions. One accepts that data have to be smoothed " before computer digestion and multivariate analysis, but to subject the results of that to the further indignity of extrapolating and 8-year follow-up to 20 years and making no estimate of the inaccuracies involved is stretching armchair epidemiology too far.
heart-disease (C.H.D.)
plasma-cholesterol and finds it greater in
to
with a high cholesterol. From this observation he deduces that the risk can be reduced by lowering the plasma-cholesterol. This is as illogical as observing that the incidence is greater in men who are bald and deducing that they would men
resistance is increased.2 There is evidence that Ca++ permeability and concentrating ability are abnormal in the sarcoplasmic reticulum (s.R.) of rats treated with 20, 25 diazacholesterol.3 Dantrolene inhibits Ca++ movement across muscle-fibre membranes. This decreases the actin-troponin-tropomyosin interaction and this decreases power.4The rationale for the trial of dantrolene was that decreased muscle power would decrease the force of the myotonia, perhaps by stabilising Ca++ permeability of the S.R. The lack of effect on myotonia does not support this hypothesis. It does reinforce the hypothesis of repetitive muscle-fibre membrane depolarisation rather than abnormal excitation-contraction coupling as the significant abnorma-
lity producing myotonia. Department of Internal Medicine, College of Medicine, University of South Florida, Tampa, St. Petersburg, U.S.A.
1.
Leelarthaepin, B., Woodhill, J. M., Palmer, A. J., Blackett, R. B. Lancet, 1974, ii, 1217. 2. Starzl, T. E., Chase, H. P., Putnam, C. W., Nora, J. J., Fennel, R. H., Jr., Porter, K. A. ibid. p. 1263. 3. Mitchell, S., Levy, R. J. ibid. p. 1263. 4. Kannel, W. J. Am. J. clin. Nutr. 1971, 24, 1074. 5. Asmal, A. C., Leary, W. P. Lancet, 1973, i, 609. 6. Beaumont, J. L., Carlson, L. A., Cooper, G. R., Fejfar, L., Fredrickson, D. S., Strasser, T. Bull. Wld Hlth Org. 1970, 43, 891.
PETER B. DUNNE PHILIP A. SINGER.
McComas, A. J., Mrozek, K. J. Neurol. Neurosurg. Psychiat. 1968, 31, 441. 2. Bryant, S. H. J. Physiol. 1969, 204, 539. 3. Seiler, D., Kuhn, E., Fiehn, W., Hasselbach, W. Eur. J. Biochem. 1970, 12, 375. 4. Putney, J. W., Jr., Bianchi, P. Fedn Proc. 1973, 32, 772. 1.
OBESITY, DIET,
AND TYPE-II
HYPERLIPIDÆMIA SIR,-Leelarthaepin et al.1 demonstrated a significant correlation between weight-reduction and lowering of plasma-cholesterol. It was perhaps unfortunate that they chose to discuss their results in terms of hyperlipidaemic types and ischaemic heart-disease. While the occurrence of premature ischaemic heartdisease in familial hyperlipidaemias such as homozygous type-IIa hyperlipoproteinaemia2 (better described as homozygous familial hypercholesterolaemia 3) is well
recognised, there is no evidence that lipoprotein estimation and typing provide a better correlation with ischaemic _heart-disease than
measurements
of cholesterol
and
triglycerides alone.4 Typing of hyperlipidaemias, as previously noted,5 represents an artificial compartmentalisation of data which cannot thus be categorised. This is indeed brought out by the observations of Leelarthaepin et al., who demonstrated a change from type-ii to type-iv hyperlipidaemia with weight-reduction. If typing has to be used at all, its use should be restricted to the familial disorders. Typing of the non-familial or exogenous disturbances in lipid metabolism merely compounds the confusion that already exists in this field. We suggest that the common varieties of non-familial hyperlipidaemias, which include hypercholesterolaemia, hypertriglyceridsemia, and variable combinations of both, should be termed idiopathic. The World Health Organisation classification 6 would thus read:
(1) Secondary hyperlipidaemias;
disorders associated with, and certain drugs
Alcohol e.g., diabetes, hypothyroidism, &c. may also be listed as secondary causes.
(2) Primary hyperlipidaemias, (a) genetic idiopathic.
or
familial, (b)
Idiopathic primary hyperlipidaemias are the variety seen commonly in people exposed to the western life style, with overnutrition, obesity, lack of exercise, and stress all acting as aetiological agents, and they are detected in most epidemiological surveys of ischaemic heart-disease. The term idiopathic is not meant to imply that a single homogenous entity is described; doubtless it will be discarded as further studies clarify the picture of the aetiology and pathogenesis of the hyperlipidasmias.
most
A. C. ASMAL W. P. LEARY.
BLOOD-CHOLESTEROL
SIR,—Professor Whyte’s attempt (April 19, a
p.
906)
to
clinical message from the Framingham study fundamental misunderstanding. He relates the
developing
coronary
J. C. BIGNALL.
DANTROLENE INEFFECTIVE IN MYOTONIC DYSTROPHY
SIR,—We should like to report a clinical trial of dantrolene sodium in a patient with myotonic dystrophy. A 50-year-old White male, as a young man had had difficulty with agility and fine hand movements. He worked as a cook in the Armed Forces and was able to function normally. He was admitted to the hospital for evaluation of slowly progressive abnormalities of gait and grip strength as well as anterior thigh pain. Examination revealed distal muscle wasting, frontal baldness, and percussion myotonia, which was confirmed by electromyographic examination. Quadriceps tenderness was also noted. There was no family history of muscle weakness, but both his father and paternal grandfather became bald early. The patient has no siblings. The quadriceps pain was thought to be secondary to repetitive muscle activity. Procainamide, phenytoin (’ Dilantin’), and quinidine were tried to no avail. Oral dantrolene sodium (100 mg. four times daily) was given for three weeks with no change in symptoms. There was no change in the myotonia either clinically or electromyographically. There was an increased number of potentials recorded from the opponens pollicis while he was exerting a 3-lb. force on a dynamometer.
deficit
CORONARY HEART-DISEASE AND
fails on risk of
The Surgery, Newport, Pembs. SA42 0TS.
Myotonia is probably due to a muscle-fibre membrane producing repetitive discharges. Although the exact nature of this defect is unknown the resting membrane potential is lower than normaland the membrane
Department of Clinical and
Experimental Pharmacology, Faculty of Medicine, University of Natal, Durban, South Africa.
extract a
benefit from wearing a wig. If he wishes to show that lowering the serum-cholesterol is beneficial then he must contrast the risk of C.H.D. between a group of men with a high cholesterol who have had it lowered and a group with a high cholesterol which is allowed to remain high. The epidemiologist may be interested to observe characteristics associated with a high risk, the clinician wants to know what evidence there is that altering the characteristic will improve the risk. Professor Whyte’s analysis is no help in answering that question. Apart from this logical lapse one cannot help but feel suspicious about his" numerical conclusions. One accepts that data have to be smoothed " before computer digestion and multivariate analysis, but to subject the results of that to the further indignity of extrapolating and 8-year follow-up to 20 years and making no estimate of the inaccuracies involved is stretching armchair epidemiology too far.
heart-disease (C.H.D.)
plasma-cholesterol and finds it greater in
to
with a high cholesterol. From this observation he deduces that the risk can be reduced by lowering the plasma-cholesterol. This is as illogical as observing that the incidence is greater in men who are bald and deducing that they would men
resistance is increased.2 There is evidence that Ca++ permeability and concentrating ability are abnormal in the sarcoplasmic reticulum (s.R.) of rats treated with 20, 25 diazacholesterol.3 Dantrolene inhibits Ca++ movement across muscle-fibre membranes. This decreases the actin-troponin-tropomyosin interaction and this decreases power.4The rationale for the trial of dantrolene was that decreased muscle power would decrease the force of the myotonia, perhaps by stabilising Ca++ permeability of the S.R. The lack of effect on myotonia does not support this hypothesis. It does reinforce the hypothesis of repetitive muscle-fibre membrane depolarisation rather than abnormal excitation-contraction coupling as the significant abnorma-
lity producing myotonia. Department of Internal Medicine, College of Medicine, University of South Florida, Tampa, St. Petersburg, U.S.A.
1.
Leelarthaepin, B., Woodhill, J. M., Palmer, A. J., Blackett, R. B. Lancet, 1974, ii, 1217. 2. Starzl, T. E., Chase, H. P., Putnam, C. W., Nora, J. J., Fennel, R. H., Jr., Porter, K. A. ibid. p. 1263. 3. Mitchell, S., Levy, R. J. ibid. p. 1263. 4. Kannel, W. J. Am. J. clin. Nutr. 1971, 24, 1074. 5. Asmal, A. C., Leary, W. P. Lancet, 1973, i, 609. 6. Beaumont, J. L., Carlson, L. A., Cooper, G. R., Fejfar, L., Fredrickson, D. S., Strasser, T. Bull. Wld Hlth Org. 1970, 43, 891.
PETER B. DUNNE PHILIP A. SINGER.
McComas, A. J., Mrozek, K. J. Neurol. Neurosurg. Psychiat. 1968, 31, 441. 2. Bryant, S. H. J. Physiol. 1969, 204, 539. 3. Seiler, D., Kuhn, E., Fiehn, W., Hasselbach, W. Eur. J. Biochem. 1970, 12, 375. 4. Putney, J. W., Jr., Bianchi, P. Fedn Proc. 1973, 32, 772. 1.
