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PREVENTION OF THROMBOSIS
695
cooperation of the Dublin health authorities, mass screening with the Guthrie test of all newborns in Dublin is planned. In the U.S.A., screening programmes have become mandatory in some States. With the
Children’s Hospital, Dublin.
S. F. CAHALANE DOREEN MURPHY.
PREVENTION OF THROMBOSIS SIR,-In your leading article (Sept. 12) you suggest
that,
since the agent in serum which produces thrombosis in experimental animals is not reduced by phenindione,l this type of anticoagulant is unsuitable for prophylaxis.
reasoning could apply to other coagulant activities anti-heparin action of serum2 and the vasculokinase activity of arterial walls,3 since neither of these is reduced by oral anticoagulants.3 But there is no firm evidence that any of these coagulant The
meprazine or of 10-15 mg. ’Frenolon ’ (N-3-/3-chlorphenothiazinil-propyl-piperazine-N-aahylium 3,4,5-trimethoxybento normal for 2-3 hours. In normal subjects and cases of hyperthyroidism, the neuroleptics did not affect the reflex-time significantly. Where the shortening of the reflex-time was due to physical work or fatigue, the effect of neuroleptics appeared to be long-continued.
zoate) the reflex-time returned
Our observations may help to avoid diagnostic errors and may open up a way for estimating circulating adrenaline. Experimental work in this direction is being
continued. National Institute for Nervous and Mental Diseases,
Budapest, Hungary.
same
-e.g., the
activities initiates thrombosis in man-which would suggest that the value of oral anticoagulants was, in fact, doubtful. It is not proved that serum thrombotic accelerator activity normally plays a part in the production of thrombosis in man. Many careful clinical trials, such as those of Sevitt and Gallagher,4have convincingly shown the success of oral anticoagulants in preventing thrombosis in clinical states
predisposed thereto. Withington Hospital, Manchester 20.
HYPOCHONDRIASIS SIR,-In your editorial (Sept. 12) you say that " hypochondriasis was coined at the end of the 18th century. "
I think it goes back much further than that. Riverius’s of Physick, published in 1661, devotes a whole chapter to Hypochondriack Melancholly " under diseases of the spleen. He aptly calls it the disgrace of physicians, because they never cure it, and the scourge of physicians, because the patients daily complain to their doctors and often change them! Apparently, for at least 300 years, some connection has been noted between hypochondriasis and the affective disorders.
Practice "
Ibstock, Leicester.
L. POLLER.
C. A. H. WATTS.
PITUITARY
THE ACHILLES REFLEX .
SIR,-After reading the stimulating article by Dr. Sherman and his colleagues,5 we applied the method they described to 50 patients with thyroid dysfunction and to 417 controls. In general our results tallied with those of Sherman et al. But our observations prompt us to make the following comments: Although the speed of the Achilles reflex depends chiefly on peripheral effect of thyroid hormone on muscular tissue, extrathyroidal factors must be considered if errors are to be the
avoided. We found that the half-relaxation time is shortened by 50-100 msec. in euthyroid persons during spontaneous hypoglycxmia, during insulin-coma treatment, in anxiety states, and during episodes of stress. The same occurs after hard physical work, and even moderate physical exercise has a significant effect: for example, in a group of 20 healthy young factory workers the half-relaxation time decreased by an average of 40 msec. after 61/2 hours’ light physical work in a sitting position. Since in all these circumstances adrenaline is mobilised in the body, we administered to 10 physically healthy subjects 1 mg. adrenaline intramuscularly and noted the changes in the speed of the Achilles reflex. In all cases the contraction-time and the half-relaxation time diminished significantly-the latter by 50-80 msec. The mean half-relaxation time, which before administration was 311 msec., fell to 247 msec. 45 minutes after administration. The adrenaline effect began after 10 minutes, in most cases reached its peak in 45 minutes, and disappeared in 2 hours. 3 hours after administration there appeared another, but lower, peak and the values returned to normal again 4 hours after administration. We believe that this second peak is due to adrenaline metabolites such as adrenochrome. Corticotrophin, cortisone, prednisolone, or noradrenaline, administered once, had no significant effect. Adrenaline administered intravenously (20 g.) decreased the reflex-time only briefly. Subsequently we studied the effect of adrenolytic neuroleptics in cases where extrathyroid factors such as anxiety and stress shortened the reflex-time. We found that 30-45 minutes after intramuscular administration of 25 mg. methotri1. Wessler, S., Reimer, S. M., Bloede, M., Nickles, M., Szalai, B. J. clin. Invest. 1960, 39, 262. 2. Poller, L. J. clin. Path. 1960, 13, 226. 3. Murray, M. Amer. J. clin. Path. 1960, 36, 500. 4. Sevitt, S., Gallagher, N. G. Lancet, 1959, ii, 981. 5. Sherman, L., Goldberg, M., Larson, F. C. ibid. 1963, i, 243.
A. GY. FEJÉR M. KUN.
GONADOTROPHIN AND DIZYGOTIC TWINNING Milham SIR,-Dr. (Sept. 12) cites the work of Gemzell, who treated 50 infertile women with gonadotrophin from human pituitary glands; half of them became pregnant and half of their pregnancies produced twins or quadruplets. Dr. Milham then musters the epidemiological and anatomical evidence in support of the view that dizygotic twinning in man may be a visible indicator of excessive maternal pituitary gonadotrophin activity. In my view the best support is given by the shape and magnitude of the pattern of excretion of oestrogen and pregnanediol induced by treatment with gonadotrophins. Ovulation of a single ovum is characterised by a sharp midcycle rise in excretion of oestriol followed by a sharp fall. This fall coincides with the rise of pregnanediol, which persists during the luteal phase of the cycle. With multiple ovulation there is a secondary rise in the excretion of oestriol which follows the pattern of excretion of pregnanediol. The height of the rise of pregnanediol is directly proportional to the amount of corpusluteum tissue, and therefore acts as a measure of the number of corpora lutea and a rough measure of the number of ova released. The height of the secondary rise of cestriol may be out of proportion with the rise of pregnanediol, indicating that more follicles have developed than have ruptured. In an extreme case there may be a massive rise in the excretion of oestriol starting at midcycle, extending uninterruptedly throughout the second half of the cycle, and unassociated with more than a flickering rise in the excretion of pregnanediol. This indicates
development of multiple follicles, none of which ruptured.l Investigation of the variables in the treatment of infertile amenorrhoeic women with human gonadotrophins has shown that not only the total dosage of follicle-stimulating hormone but also the dosage and timing of treatment with luteinising substance is important in producing these different patterns of excretion. As a result of this experience, multiple ovulation with dizygotic twins occurred in our lst patient only. 6 others had single babies, and 2 miscarried out of a total of 13 who have been treated with human gonadotrophins.23 the
These
J.
findings
suggest that the size, the
quality, and
Crooke, A. C. Proc. R. Soc. Med. 1964, 57, 111. Crooke, A. C., Butt, W. R., Palmer, R. F., Morris, R., Logan Edwards, R., Anson, C. J. J. Obstet. Gynæc. Brit. Commonw. 1963, 70, 604. 3. Crooke, A. C., Butt, W. R., Palmer, R. F., Bertrand, P. V., Carrington, S. P., Logan Edwards, R., Anson, C. J. ibid. 1964, 71, 571. 1. 2.
cooperation of the Dublin health authorities, mass screening with the Guthrie test of all newborns in Dublin is planned. In the U.S.A., screening programmes have become mandatory in some States. With the
Children’s Hospital, Dublin.
S. F. CAHALANE DOREEN MURPHY.
PREVENTION OF THROMBOSIS SIR,-In your leading article (Sept. 12) you suggest
that,
since the agent in serum which produces thrombosis in experimental animals is not reduced by phenindione,l this type of anticoagulant is unsuitable for prophylaxis.
reasoning could apply to other coagulant activities anti-heparin action of serum2 and the vasculokinase activity of arterial walls,3 since neither of these is reduced by oral anticoagulants.3 But there is no firm evidence that any of these coagulant The
meprazine or of 10-15 mg. ’Frenolon ’ (N-3-/3-chlorphenothiazinil-propyl-piperazine-N-aahylium 3,4,5-trimethoxybento normal for 2-3 hours. In normal subjects and cases of hyperthyroidism, the neuroleptics did not affect the reflex-time significantly. Where the shortening of the reflex-time was due to physical work or fatigue, the effect of neuroleptics appeared to be long-continued.
zoate) the reflex-time returned
Our observations may help to avoid diagnostic errors and may open up a way for estimating circulating adrenaline. Experimental work in this direction is being
continued. National Institute for Nervous and Mental Diseases,
Budapest, Hungary.
same
-e.g., the
activities initiates thrombosis in man-which would suggest that the value of oral anticoagulants was, in fact, doubtful. It is not proved that serum thrombotic accelerator activity normally plays a part in the production of thrombosis in man. Many careful clinical trials, such as those of Sevitt and Gallagher,4have convincingly shown the success of oral anticoagulants in preventing thrombosis in clinical states
predisposed thereto. Withington Hospital, Manchester 20.
HYPOCHONDRIASIS SIR,-In your editorial (Sept. 12) you say that " hypochondriasis was coined at the end of the 18th century. "
I think it goes back much further than that. Riverius’s of Physick, published in 1661, devotes a whole chapter to Hypochondriack Melancholly " under diseases of the spleen. He aptly calls it the disgrace of physicians, because they never cure it, and the scourge of physicians, because the patients daily complain to their doctors and often change them! Apparently, for at least 300 years, some connection has been noted between hypochondriasis and the affective disorders.
Practice "
Ibstock, Leicester.
L. POLLER.
C. A. H. WATTS.
PITUITARY
THE ACHILLES REFLEX .
SIR,-After reading the stimulating article by Dr. Sherman and his colleagues,5 we applied the method they described to 50 patients with thyroid dysfunction and to 417 controls. In general our results tallied with those of Sherman et al. But our observations prompt us to make the following comments: Although the speed of the Achilles reflex depends chiefly on peripheral effect of thyroid hormone on muscular tissue, extrathyroidal factors must be considered if errors are to be the
avoided. We found that the half-relaxation time is shortened by 50-100 msec. in euthyroid persons during spontaneous hypoglycxmia, during insulin-coma treatment, in anxiety states, and during episodes of stress. The same occurs after hard physical work, and even moderate physical exercise has a significant effect: for example, in a group of 20 healthy young factory workers the half-relaxation time decreased by an average of 40 msec. after 61/2 hours’ light physical work in a sitting position. Since in all these circumstances adrenaline is mobilised in the body, we administered to 10 physically healthy subjects 1 mg. adrenaline intramuscularly and noted the changes in the speed of the Achilles reflex. In all cases the contraction-time and the half-relaxation time diminished significantly-the latter by 50-80 msec. The mean half-relaxation time, which before administration was 311 msec., fell to 247 msec. 45 minutes after administration. The adrenaline effect began after 10 minutes, in most cases reached its peak in 45 minutes, and disappeared in 2 hours. 3 hours after administration there appeared another, but lower, peak and the values returned to normal again 4 hours after administration. We believe that this second peak is due to adrenaline metabolites such as adrenochrome. Corticotrophin, cortisone, prednisolone, or noradrenaline, administered once, had no significant effect. Adrenaline administered intravenously (20 g.) decreased the reflex-time only briefly. Subsequently we studied the effect of adrenolytic neuroleptics in cases where extrathyroid factors such as anxiety and stress shortened the reflex-time. We found that 30-45 minutes after intramuscular administration of 25 mg. methotri1. Wessler, S., Reimer, S. M., Bloede, M., Nickles, M., Szalai, B. J. clin. Invest. 1960, 39, 262. 2. Poller, L. J. clin. Path. 1960, 13, 226. 3. Murray, M. Amer. J. clin. Path. 1960, 36, 500. 4. Sevitt, S., Gallagher, N. G. Lancet, 1959, ii, 981. 5. Sherman, L., Goldberg, M., Larson, F. C. ibid. 1963, i, 243.
A. GY. FEJÉR M. KUN.
GONADOTROPHIN AND DIZYGOTIC TWINNING Milham SIR,-Dr. (Sept. 12) cites the work of Gemzell, who treated 50 infertile women with gonadotrophin from human pituitary glands; half of them became pregnant and half of their pregnancies produced twins or quadruplets. Dr. Milham then musters the epidemiological and anatomical evidence in support of the view that dizygotic twinning in man may be a visible indicator of excessive maternal pituitary gonadotrophin activity. In my view the best support is given by the shape and magnitude of the pattern of excretion of oestrogen and pregnanediol induced by treatment with gonadotrophins. Ovulation of a single ovum is characterised by a sharp midcycle rise in excretion of oestriol followed by a sharp fall. This fall coincides with the rise of pregnanediol, which persists during the luteal phase of the cycle. With multiple ovulation there is a secondary rise in the excretion of oestriol which follows the pattern of excretion of pregnanediol. The height of the rise of pregnanediol is directly proportional to the amount of corpusluteum tissue, and therefore acts as a measure of the number of corpora lutea and a rough measure of the number of ova released. The height of the secondary rise of cestriol may be out of proportion with the rise of pregnanediol, indicating that more follicles have developed than have ruptured. In an extreme case there may be a massive rise in the excretion of oestriol starting at midcycle, extending uninterruptedly throughout the second half of the cycle, and unassociated with more than a flickering rise in the excretion of pregnanediol. This indicates
development of multiple follicles, none of which ruptured.l Investigation of the variables in the treatment of infertile amenorrhoeic women with human gonadotrophins has shown that not only the total dosage of follicle-stimulating hormone but also the dosage and timing of treatment with luteinising substance is important in producing these different patterns of excretion. As a result of this experience, multiple ovulation with dizygotic twins occurred in our lst patient only. 6 others had single babies, and 2 miscarried out of a total of 13 who have been treated with human gonadotrophins.23 the
These
J.
findings
suggest that the size, the
quality, and
Crooke, A. C. Proc. R. Soc. Med. 1964, 57, 111. Crooke, A. C., Butt, W. R., Palmer, R. F., Morris, R., Logan Edwards, R., Anson, C. J. J. Obstet. Gynæc. Brit. Commonw. 1963, 70, 604. 3. Crooke, A. C., Butt, W. R., Palmer, R. F., Bertrand, P. V., Carrington, S. P., Logan Edwards, R., Anson, C. J. ibid. 1964, 71, 571. 1. 2.