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MYALGIA AND AN ORAL CONTRACEPTIVE
1187 I-COMPARISON
OF A.M.P.S. IN RHEUMATIC AND VALVULAR DISEASE AND NORMAL HEART-VALVE
TABLE
BACTERIAL
pain recurred in exactly the same places as before. After again discontinuing the drug the pain subsided gradually within 2 weeks. The association may have been fortuitous, but, if so, it is remarkable that it occurred on two separate occasions. Shotley Bridge General Hospital, D. M. DAVIES Annfield Plain, co. Durham. J. F. LUND.
*
Average of 14 normal valves of
same
t !-tg. of uronic acid in
A.M.P.S. per
t Ratio of carbazole
orcinol.
to
age-group. 100 mg. dry tissue.
of 14 cases). The content of A.M.P.S. was notably less in both aortic and mitral valves than in controls in this age-group, and changes in the carbazole/orcinol ratio of uronic acid in A.M.P.S. of the diseased tissues were noted. Indeed, the fractionation of A.M.P.S. in the mitral valve indicated that this decrease of A.M.P.S. is due entirely to the loss of hyaluronic acid (H.A.) (table 11). Human heart-valves were shown to have a high H.A. value, compared with pig and bovine heart-valves, and this remained unchanged from the age of 20 to over 60 years.3 TABLE II-A.M.P.S. COMPOSITIONS IN RHEUMATIC AND BACTERIAL VALVE
DISEASE AND NORMAL MITRAL VALVES
connective tissues, the changes of A.M.P.S. in pathoconditions resemble those found in the ageing process; such a finding was seen in the herniated disc reported by Davidson and Woodhall.4 In contrast, the change in A.M.P.S. in the heart-valve of rheumatic valvular disease was substantially different from that in the ageing valve, where the relative proportion of H.A. remained high.3 These findings suggest that the change in A.M.P.S. in rheumatic and bacterial valvular disease may not be the result of the pathological processes, but may yet be related to it, if not causally. These findings are so far unexplained. Department of Pathology, SHINICHIRO TORII Albert Einstein College of Medicine, KOMEI NAKAO Bronx, N.Y. 10461, ALFRED A. ANGRIST. U.S.A. In
some
logical
MYALGIA AND AN ORAL CONTRACEPTIVE SIR,-We report here a myalgic syndrome, possibly induced by the oral contraceptive, ’Ovulen ’. Neither we nor the manufacturers are aware of any previously reported case of this kind. A woman of 27 years took the oral contraceptiveConovid-E’, a mixture of norethynodrel and mestranol (ethinyloestradiol 3methyl ether), from April, 1963, to November, 1964. She then gave up the preparation because of break-through bleeding, and began to take instead another oral contraceptive, Ovulen ’, a mixture of ethynodiol diacetate and mestranol. On Jan. 13, 1965, aching pain developed in the lateral side of the upper third of both legs, and, a week later, similar aching pain over the upper part of the extensor muscles of both forearms. The pain in the limbs was aggravated by muscular movement, and she likened it to the muscular discomfort which follows unaccustomed exercise. She was afebrile. There was localised muscle tenderness in the areas mentioned, but no other abnormal signs-in particular no oedema of the limbs or evidence of superficial or deep venous thrombosis. After she stopped taking the oral contraceptive, the patient’s pain gradually subsided over a period of 2 weeks. In March, 1965, she decided to try ovulen again, but after 2 weeks the 4. Davidson, E. A., Woodhall, B. J. biol. Chem. 1959, 234, 2951. "
"
TREATMENT OF DIPHTHERIA SIR,-Diphtheria varies greatly in its clinical forms from place to place and from time to time. Dr. Gandhi (Nov. 20) found in Bombay that doses of antitoxin not exceeding 20,000 units in his group-B cases gave as good results as up to 1,000,000 units in his group-A cases. I am not familiar with this classification, but would guess that neither his group-A nor his cases included malignant or hypertoxic clinical forms, characterised inter alia by extensive faucial and pharyngeal membrane, thin and filmy at the rapidly spreading edges, covering the uvula and parts of the soft and hard palates and
group-B
pharyngeal wall, and accompanied by gross painless periadenitis (" bull neck "). This is the type of case for which at least 100,000 units of antitoxin intravenously was recommended in my book to which Dr. Gandhi refers.l If he ever meets this form he will find that myocarditis is invariably present and that the mortality of cases treated with small doses-e.g., 20,000 units of antitoxin intramuscularly-will approximate to 100%. A malignant form of this kind invaded parts of Great Britain such as Leeds and Leicester, and Central Europe, for one or more years at a time, before general immunisation against the disease was practised; there was a coincidental large increase of strains of the gravis or intermedius types of Corynebacterium diphtheriae in the community. Although these strains persisted for a time, there was later a pronounced decrease in clinical hypertoxic forms. A fair proportion of these hypertoxic patients will recover after a stormy course if treated with large doses of antitoxin intravenously on or before the third day of the disease. H. STANLEY BANKS. Leatherhead, Surrey. not taken into account the of the membrane and the grade of toxicity, and I do not think his study is conclusive. My five years’ experience with the treatment of diphtheria cases (1959-64), all the year round, shows that there is a definite relation between the dosage and these two factors. We also have to remember that the administration of antidiphtheritic serum is preventive rather than curative. Doha, Quatar, r. SYED ABDUL
SIR,-Dr. Gandhi (Nov. 20) has
extent
ArabianGulf.
A
QAWI.
HYPERTHYROIDISM AND PREDNISONE SiR,—The article by Professor Werner and Dr. Platman (Oct. 16) adds to our increasing knowledge of the metabolic relation between the thyroid and adrenal glands. My co-workers and I reported2 that cortisone reduced the hypercalcxmia accompanying thyrotoxicosis: similar results have now been observed in two other cases. Brown and Lowman3 have noted that thyrotoxicosis develops not infrequently in patients on corticosteroids for other (autoimmune) diseases. In retrospect, we recalled that our patient,2 too, had previously been on long-term steroid therapy for rheumatoid arthritis, and that his thyrotoxic hypercalcxmia was first noted when his steroid dosage was reduced; we wondered4 whether immune responses might be involved in such cases. Professor Werner and Dr. Platman’s work demonstrating that long-acting thyroid stimulator (L.A.T.S.) may be an antibody having an xtiological role in the production of Graves’ disease, 1.
Banks, H. S. Modern Practice in Infectious Fevers; vol. I. London, 1951.
Sataline, L. R., Powell, C. P., Hamwi, G. New Engl. J. Med. 1962, 267, 646. 3. Brown, D. M., Lowman, J. T. ibid. 1964, 270, 278. 4. Sataline, L. R. ibid. p. 691. 2.
OF A.M.P.S. IN RHEUMATIC AND VALVULAR DISEASE AND NORMAL HEART-VALVE
TABLE
BACTERIAL
pain recurred in exactly the same places as before. After again discontinuing the drug the pain subsided gradually within 2 weeks. The association may have been fortuitous, but, if so, it is remarkable that it occurred on two separate occasions. Shotley Bridge General Hospital, D. M. DAVIES Annfield Plain, co. Durham. J. F. LUND.
*
Average of 14 normal valves of
same
t !-tg. of uronic acid in
A.M.P.S. per
t Ratio of carbazole
orcinol.
to
age-group. 100 mg. dry tissue.
of 14 cases). The content of A.M.P.S. was notably less in both aortic and mitral valves than in controls in this age-group, and changes in the carbazole/orcinol ratio of uronic acid in A.M.P.S. of the diseased tissues were noted. Indeed, the fractionation of A.M.P.S. in the mitral valve indicated that this decrease of A.M.P.S. is due entirely to the loss of hyaluronic acid (H.A.) (table 11). Human heart-valves were shown to have a high H.A. value, compared with pig and bovine heart-valves, and this remained unchanged from the age of 20 to over 60 years.3 TABLE II-A.M.P.S. COMPOSITIONS IN RHEUMATIC AND BACTERIAL VALVE
DISEASE AND NORMAL MITRAL VALVES
connective tissues, the changes of A.M.P.S. in pathoconditions resemble those found in the ageing process; such a finding was seen in the herniated disc reported by Davidson and Woodhall.4 In contrast, the change in A.M.P.S. in the heart-valve of rheumatic valvular disease was substantially different from that in the ageing valve, where the relative proportion of H.A. remained high.3 These findings suggest that the change in A.M.P.S. in rheumatic and bacterial valvular disease may not be the result of the pathological processes, but may yet be related to it, if not causally. These findings are so far unexplained. Department of Pathology, SHINICHIRO TORII Albert Einstein College of Medicine, KOMEI NAKAO Bronx, N.Y. 10461, ALFRED A. ANGRIST. U.S.A. In
some
logical
MYALGIA AND AN ORAL CONTRACEPTIVE SIR,-We report here a myalgic syndrome, possibly induced by the oral contraceptive, ’Ovulen ’. Neither we nor the manufacturers are aware of any previously reported case of this kind. A woman of 27 years took the oral contraceptiveConovid-E’, a mixture of norethynodrel and mestranol (ethinyloestradiol 3methyl ether), from April, 1963, to November, 1964. She then gave up the preparation because of break-through bleeding, and began to take instead another oral contraceptive, Ovulen ’, a mixture of ethynodiol diacetate and mestranol. On Jan. 13, 1965, aching pain developed in the lateral side of the upper third of both legs, and, a week later, similar aching pain over the upper part of the extensor muscles of both forearms. The pain in the limbs was aggravated by muscular movement, and she likened it to the muscular discomfort which follows unaccustomed exercise. She was afebrile. There was localised muscle tenderness in the areas mentioned, but no other abnormal signs-in particular no oedema of the limbs or evidence of superficial or deep venous thrombosis. After she stopped taking the oral contraceptive, the patient’s pain gradually subsided over a period of 2 weeks. In March, 1965, she decided to try ovulen again, but after 2 weeks the 4. Davidson, E. A., Woodhall, B. J. biol. Chem. 1959, 234, 2951. "
"
TREATMENT OF DIPHTHERIA SIR,-Diphtheria varies greatly in its clinical forms from place to place and from time to time. Dr. Gandhi (Nov. 20) found in Bombay that doses of antitoxin not exceeding 20,000 units in his group-B cases gave as good results as up to 1,000,000 units in his group-A cases. I am not familiar with this classification, but would guess that neither his group-A nor his cases included malignant or hypertoxic clinical forms, characterised inter alia by extensive faucial and pharyngeal membrane, thin and filmy at the rapidly spreading edges, covering the uvula and parts of the soft and hard palates and
group-B
pharyngeal wall, and accompanied by gross painless periadenitis (" bull neck "). This is the type of case for which at least 100,000 units of antitoxin intravenously was recommended in my book to which Dr. Gandhi refers.l If he ever meets this form he will find that myocarditis is invariably present and that the mortality of cases treated with small doses-e.g., 20,000 units of antitoxin intramuscularly-will approximate to 100%. A malignant form of this kind invaded parts of Great Britain such as Leeds and Leicester, and Central Europe, for one or more years at a time, before general immunisation against the disease was practised; there was a coincidental large increase of strains of the gravis or intermedius types of Corynebacterium diphtheriae in the community. Although these strains persisted for a time, there was later a pronounced decrease in clinical hypertoxic forms. A fair proportion of these hypertoxic patients will recover after a stormy course if treated with large doses of antitoxin intravenously on or before the third day of the disease. H. STANLEY BANKS. Leatherhead, Surrey. not taken into account the of the membrane and the grade of toxicity, and I do not think his study is conclusive. My five years’ experience with the treatment of diphtheria cases (1959-64), all the year round, shows that there is a definite relation between the dosage and these two factors. We also have to remember that the administration of antidiphtheritic serum is preventive rather than curative. Doha, Quatar, r. SYED ABDUL
SIR,-Dr. Gandhi (Nov. 20) has
extent
ArabianGulf.
A
QAWI.
HYPERTHYROIDISM AND PREDNISONE SiR,—The article by Professor Werner and Dr. Platman (Oct. 16) adds to our increasing knowledge of the metabolic relation between the thyroid and adrenal glands. My co-workers and I reported2 that cortisone reduced the hypercalcxmia accompanying thyrotoxicosis: similar results have now been observed in two other cases. Brown and Lowman3 have noted that thyrotoxicosis develops not infrequently in patients on corticosteroids for other (autoimmune) diseases. In retrospect, we recalled that our patient,2 too, had previously been on long-term steroid therapy for rheumatoid arthritis, and that his thyrotoxic hypercalcxmia was first noted when his steroid dosage was reduced; we wondered4 whether immune responses might be involved in such cases. Professor Werner and Dr. Platman’s work demonstrating that long-acting thyroid stimulator (L.A.T.S.) may be an antibody having an xtiological role in the production of Graves’ disease, 1.
Banks, H. S. Modern Practice in Infectious Fevers; vol. I. London, 1951.
Sataline, L. R., Powell, C. P., Hamwi, G. New Engl. J. Med. 1962, 267, 646. 3. Brown, D. M., Lowman, J. T. ibid. 1964, 270, 278. 4. Sataline, L. R. ibid. p. 691. 2.