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MALARIA IN NORTHERN CLIMES
728 are not segregated from the rest of the but share the same mess-rooms and sittingrooms. Their leisure is more controlled : they may attend dances, but tennis is forbidden, and they must be in by 10.30 P.M. unless they have the medical superintendent’s permission to stay out later. Moreover, they It must be recogare a much-valued section of the staff. nised, however, that the aim in the two schemes was rather different : Dr. Kissen set out with the deliberate intention of reabling convalescent patients, whereas Dr. Watt employs only patients who are thoroughly fit. Dr. Kissen’s experiment has been useful in drawing attention to the special difficulties encountered when a reablement scheme is attempted in a sanatorium mainly staffed by full-time healthy nurses.
work ; they nurses
CASTRATION AND ŒSTROGEN
IN
PROSTATIC
CANCER
No-ONE now doubts that in prostatic cancer temporary relief can be obtained from either castration or the administration of oestrogen. Yet the rationale of these procedures remains in part unknown. Either of them, though in different ways, will check the supply of androgen on which the development, maintenance, and of the normal prostate depend: oestrogens will reduce the supply of pituitary gonadotrophin and so inhibit the capacity of the testicles to supply androgen, whereas castration will cut off the supply of androgen directly. And any condition in which the concentration of androgen in the blood is greatly diminished will be accompanied by ischaemia and atrophy of the prostate gland and other accessory male genital organs. It seems reasonable to assume that the consequent shrinkage of these organs would at once lower the tension in the affected parts and so alleviate pain, and that the local ischaemia would retard the growth of a tumour. An inquiring man, however, will wonder whether such a simple explanation He may ask if a malignant covers the whole problem. in the is ever, growth prostate apart from the bloodsupply, to some degree dependent on androgen for its vigour. Cancer cells are usually regarded as uncontrolled by the tissues of the host ; but this may not be a universal rule. Malignancy varies in degree, and it is conceivable that some cancer cells are not so entirely undifferentiated as to be irresponsive to the normal hormones. Some clinicians regard the giving of oestrogen to patients with prostatic cancer as a more potent remedy than castration, though castration is the readier way to stop the main supply of androgen. If this view is correct, oestrogen must exert some beneficial effect which removal of the testicles does not afford. Possibly oestrogen curtails the output of androgen by the adrenals as well as by the testicles, whereas castration would not have this effect. Meanwhile it has to be remembered that no general anticarcinogenic property has been demonstrated in oestrogen, the reactions to which are mainly confined to those tissues which it regulates in health-namely, the organs concerned with reproduction. Elsewhere in this issue Dr. Ludford and Dr. Dmochowski report that stilbcestrol had no specific inhibitory effect on growth of the mouse tumours used in their experiments. (Estrogens, however, possess the capacity of increasing the connective-tissue stroma, with an excessive deposition of collagen, in many organs of the body, including the prostate. This reaction has been recorded by numerous observers and has been discussed with abundant histological detail by Mosinger1 in a comprehensive monograph based on the results of giving large doses of oestrogen weekly to guineapigs. The practical importance of this reaction needs further experiment in connexion with the treatment of cancer ; for it has been thought on reasonable grounds that the speed of neoplasia may
activity
1.
Mosinger, M.
Le Problème du Cancer, Paris, 1946.
occasionally be restricted by the local development of fibrous tissue-in fact, deposits of collagen have seemed to represent a definite, if ineffectual, curative attempt. Until this point has been quite elucidated, these considerations suggest that a combination of castration with the administration of oestrogen may be more beneficial in prostatic cancer than either remedy used alone. MALARIA
IN
NORTHERN CLIMES
THE spread of malaria as an endemic disease is limited by temperature, the northern limit for benign tertian and for quartan malaria in Europe being the summer isotherm of 60°F, and that for malignant tertian 70OF.l Temperature also governs the development of the sexual form of the plasmodium in the mosquito. This development takes 10-14 days at a temperature of 77°F and 14-18 days at a somewhat lower temperature, and does not take place at all if the temperature is permanently below 59°F.2 Moreover, in temperate climates malaria tends to have peaks in spring and autumn. Swellengrebel and De Buck3 showed that, in the Netherlands, the spring peak was due to infection which had been acquired the previous autumn and had remained latent during the winter. An even longer incubation has been fully proved by Hernberg’s account2 of the outbreaks of tertian malaria in Finland, which lies north of the summer isotherm of 60°F-i.e., beyond the bounds of endemic malaria. Finland had been almost entirely free from malaria for about twenty years when the infection was reintroduced there during the late war by Finns who had been fighting the Russians. By the end of the summer of 1941, 57 isolated cases had been reported ; there were 583 cases in 1942, 262 in 1943, and 892 in 1944. These were nearly all in soldiers. The civilian cases numbered none in 1941, 75 in 1942, 53 in 1943, and 17 in 1944 ; and some of these patients were probably demobilised soldiers. After general demobilisation in 1945, however, there was a great spread of malaria among civilians, the total for 1945 being estimated as 1252 cases, excluding relapses. Hernberg investigated 856 of these cases. In spite of the high susceptibility of children to malaria there were no cases in children under 15 years of age, and there were not many in youngsters of 15-20. The seasonal incidence is illuminating. Between February and April, 1945, the mosquito-free period, there were 142 cases, and the peak of incidence was in May (440 cases) and June (352 cases), whereas in July and August, while mosquitoes were most abundant, the number of cases fell off rapidly. Hernberg says :
days must be assigned in Finland to full of a complete picture of disease in transmission of infection from man to man via the mosquito, half the number of cases would have been infected already before the middle of April-i.e., before there were any mosquitoes at all-providing the infection had occurred in that year." "As 24-36
development
The seasonal incidence and the great preponderance of cases show that most of the patients must have been infected the previous year while in military service elsewhere. Further, the geographical incidence in many cases was too disconnected for infection to have arisen where the malaria developed ; and in some districts the summer temperature was too low to permit infection by mosquito bites that year. The view that infection came from hibernating mosquitoes is put out of court by the appearance of malaria in districts which had been free the year before. A questionary sent to 868 patients showed that all but 13 of the 596 who replied had been in military service the previous year in the
military
Christophers, S. R. British Encyclopædia of Medical Practice, London, 1938, vol. VIII, p. 304. 2. Hernberg, C. A. Acta med. scand. 1947, 127, 342. 3. Swellengrebel. N. H., De Buck, A. Malaria in the Netherlands, London, 1938 ; see also Lancet, 1938, ii, 894. 1.
729 Karelian Isthmus, where there had then been much malaria,. The possibility of an epidemic of benign tertian malaria in England owing to the return of soldiers treated with mepacrine has already been discussed in these columns. In the Finnish cases the incubationperiod must have been 6-14 months, unless the cases A long winter incubation in man is not were relapses. likely to arise in cases of malaria developing in England, where the temperature lies well within the thermal boundaries of endemic malaria. CARE OF THE AGED IN DENMARK
DENMARK was the first country to introduce the of free provision for the old. In his address to the International Conference of Physicians on Sept. 9 Dr. Johs. Frandsen noted that the Danish Old Age Relief Act of 1891 differentiated clearly between support in old age and help to the poor, though the extent of relief to the old was left to the discretion of local authorities. In 1922, however, the last flavour of poorlaw was removed from the Act, and " old-age relief became the old-age pension. It is paid to men over 65 and women over 60 whose income is below a prescribed level, provided they have a clean police record for the previous five years and have not lived lives offensive to public morals ; presumably those whofail in these respects are relieved in other ways. The amount of the pension is a basic sum calculated on the cost of living in the capital, the provincial towns, and the country districts. Thus a married couple receive about f1l5 a year in Copenhagen, JE98 in provincial towns, and f83 in country areas ; this amounts to about 46% of the average net income of an unskilled worker. The sum varies with the cost of living, and there are various supplements-for example, a children’s allowance for those who are responsible for children under the age of 17, fuel and clothing supplements, and a personal supplement for those with special difficulties. Of Denmark’s 4 million inhabitants some 200,000 are at present drawing the pension. As in England, there are both voluntary and municipal homes for the old. The council homes are exclusively for pensioners, the pensions being paid to the homes with the proviso that the old people are to live under conditions as good as they could buy with their pensions elsewhere. Entrance to the homes is voluntary, and the old people usually take their own furniture in with them ; they can prepare meals in a common kitchen, and suitable interests and occupations are provided. Most of the voluntary homes were founded before legislation for the old was introduced. Though small properly equipped flats are the most suitable homes for old people living alone, they are expensive to provide, and the Danish housing problem is as acute as our own. There are, however, some blocks of flats for old people, built by the local authorities before the war. A woman inspector lives in each block to help and look after the old people, and in many of the blocks there are assembly rooms for concerts and celebrations. In 1942 there was accommodation, in voluntary and municipal homes and in flats, for some 25,000 old-age pensioners throughout the country. In Copenhagen most of them are housed in flats ; but it is estimated that 285 "places" per 1000 pensioners are needed in Copenhagen ; while in other towns the figure is put at 250, and in rural areas at 200 per 1000. Most of the homes have a sick-bay, and the largest of them has a hospital with a full-time medical officer. In other homes the old people can choose their own doctor, but if they have no preference they are attended by one appointed by the local authority.
principle
4. Lancet,
1945, ii, 49.
"THEY ORDER THIS MATTER FRANCE"
BETTER IN
THE tendency in France to elevate therapeutics into art in its own right has led at times to a finical refinement ill suited to crowded evening surgeries. Perhaps we in this country have erred in a contrary sense in guiding our treatment by its apparent effect on the patient, without much theoretical consideration of the modus operandi of the remedy. In the case of penicillin the charge of pragmatism will not lie against us ; but it is interesting to note the methods of our French colleagues in handling a drug of which our experience is somewhat longer than theirs. A paper by Mollaret1 on guiding principles in the use of antibiotics makes three major suggestions. The first is that, so far from decreasing as treatment proceeds, the dose should be maintained at its original high level; by this means he hopes to discourage the organism from becoming penicillin-resistant. (We doubt if, in this country, penicillin dosage is often arranged on a decreasing scale, since it is recognised by most users that a drug so rapidly excreted can be kept at optimum levels only by continuous or repeated dosage-in contrast to sulphonamide therapy, for example, where a large initial dose allows a high concentration to be built up which may be maintained by subsequent smaller doses.) His second suggestion is that the final dose should be double that administered previously, so that it shall give the coup-degrace to any organism that still resists. Since the concentration in the tissues is usually in excess of that required to deal with the organisms, the advantage of this procedure is questionable ; but certainly nothing is lost by it beyond a few hundred thousand units of penicillin. Thirdly, and most ingeniously, he suggests that by giving penicillinase after the last dose of penicillin it may be possible to avoid creating a residue of drugfast organisms at the end of treatment. This, however, seems to be a case of pursuing logic altogether too far. That strains of organisms exposed in vitro for many generations to sublethal concentrations of penicillin may become resistant to penicillin nobody doubts ; but that this resistance will develop in the few hours while the last remnants of a therapeutic dose are being excreted from the body seems most unlikely. In fact resistance to penicillin seems to develop only rarely under therapeutic conditions, and may best be avoided by attention to Mollaret’s first suggestion. Though the last words on the administration of penicillin have yet to be said, we do not yet see reason to echo here the dictum of the Rev. L. Sterne. an
DEATH ON THE ROAD METHODS of reducing road accidents still need much study. Mr. J. S. Dean, in a recent book,2 makes some interesting and meritorious suggestions for reducing these accidents. The installation of governors on vehicles subjected to a general speed-limit would doubtless be beneficial, though the manufacture of any mechanical device presents difficulties at the present moment. Footpaths beside all roads are also desirable, but the arrears of road maintenance which piled up during the war years will use up most of the money available for the improvement of highways for a considerable time to Mr. Dean notes that in 1937 private cars were come. involved in 33-2% of the total road accidents, public conveyances in 6-8%, and commercial vehicles in 14-3% ; and he concludes that private cars have the worst accident record. This hardly tallies, however, with the car-mileages he gives for these different types of vehicles, which have the ratios of 14-40 : 3-04 : 7-18. Private 1. Mollaret, P. Bull. Soc. méd. Hôp. Paris, 1947, 63, 643. 2. Murder Most Foul. A study of the road deaths problem. London : Published for the Public Affairs News Service by George Allen & Unwin. 1947. Pp. 114. 3s. 6d.
work ; they nurses
CASTRATION AND ŒSTROGEN
IN
PROSTATIC
CANCER
No-ONE now doubts that in prostatic cancer temporary relief can be obtained from either castration or the administration of oestrogen. Yet the rationale of these procedures remains in part unknown. Either of them, though in different ways, will check the supply of androgen on which the development, maintenance, and of the normal prostate depend: oestrogens will reduce the supply of pituitary gonadotrophin and so inhibit the capacity of the testicles to supply androgen, whereas castration will cut off the supply of androgen directly. And any condition in which the concentration of androgen in the blood is greatly diminished will be accompanied by ischaemia and atrophy of the prostate gland and other accessory male genital organs. It seems reasonable to assume that the consequent shrinkage of these organs would at once lower the tension in the affected parts and so alleviate pain, and that the local ischaemia would retard the growth of a tumour. An inquiring man, however, will wonder whether such a simple explanation He may ask if a malignant covers the whole problem. in the is ever, growth prostate apart from the bloodsupply, to some degree dependent on androgen for its vigour. Cancer cells are usually regarded as uncontrolled by the tissues of the host ; but this may not be a universal rule. Malignancy varies in degree, and it is conceivable that some cancer cells are not so entirely undifferentiated as to be irresponsive to the normal hormones. Some clinicians regard the giving of oestrogen to patients with prostatic cancer as a more potent remedy than castration, though castration is the readier way to stop the main supply of androgen. If this view is correct, oestrogen must exert some beneficial effect which removal of the testicles does not afford. Possibly oestrogen curtails the output of androgen by the adrenals as well as by the testicles, whereas castration would not have this effect. Meanwhile it has to be remembered that no general anticarcinogenic property has been demonstrated in oestrogen, the reactions to which are mainly confined to those tissues which it regulates in health-namely, the organs concerned with reproduction. Elsewhere in this issue Dr. Ludford and Dr. Dmochowski report that stilbcestrol had no specific inhibitory effect on growth of the mouse tumours used in their experiments. (Estrogens, however, possess the capacity of increasing the connective-tissue stroma, with an excessive deposition of collagen, in many organs of the body, including the prostate. This reaction has been recorded by numerous observers and has been discussed with abundant histological detail by Mosinger1 in a comprehensive monograph based on the results of giving large doses of oestrogen weekly to guineapigs. The practical importance of this reaction needs further experiment in connexion with the treatment of cancer ; for it has been thought on reasonable grounds that the speed of neoplasia may
activity
1.
Mosinger, M.
Le Problème du Cancer, Paris, 1946.
occasionally be restricted by the local development of fibrous tissue-in fact, deposits of collagen have seemed to represent a definite, if ineffectual, curative attempt. Until this point has been quite elucidated, these considerations suggest that a combination of castration with the administration of oestrogen may be more beneficial in prostatic cancer than either remedy used alone. MALARIA
IN
NORTHERN CLIMES
THE spread of malaria as an endemic disease is limited by temperature, the northern limit for benign tertian and for quartan malaria in Europe being the summer isotherm of 60°F, and that for malignant tertian 70OF.l Temperature also governs the development of the sexual form of the plasmodium in the mosquito. This development takes 10-14 days at a temperature of 77°F and 14-18 days at a somewhat lower temperature, and does not take place at all if the temperature is permanently below 59°F.2 Moreover, in temperate climates malaria tends to have peaks in spring and autumn. Swellengrebel and De Buck3 showed that, in the Netherlands, the spring peak was due to infection which had been acquired the previous autumn and had remained latent during the winter. An even longer incubation has been fully proved by Hernberg’s account2 of the outbreaks of tertian malaria in Finland, which lies north of the summer isotherm of 60°F-i.e., beyond the bounds of endemic malaria. Finland had been almost entirely free from malaria for about twenty years when the infection was reintroduced there during the late war by Finns who had been fighting the Russians. By the end of the summer of 1941, 57 isolated cases had been reported ; there were 583 cases in 1942, 262 in 1943, and 892 in 1944. These were nearly all in soldiers. The civilian cases numbered none in 1941, 75 in 1942, 53 in 1943, and 17 in 1944 ; and some of these patients were probably demobilised soldiers. After general demobilisation in 1945, however, there was a great spread of malaria among civilians, the total for 1945 being estimated as 1252 cases, excluding relapses. Hernberg investigated 856 of these cases. In spite of the high susceptibility of children to malaria there were no cases in children under 15 years of age, and there were not many in youngsters of 15-20. The seasonal incidence is illuminating. Between February and April, 1945, the mosquito-free period, there were 142 cases, and the peak of incidence was in May (440 cases) and June (352 cases), whereas in July and August, while mosquitoes were most abundant, the number of cases fell off rapidly. Hernberg says :
days must be assigned in Finland to full of a complete picture of disease in transmission of infection from man to man via the mosquito, half the number of cases would have been infected already before the middle of April-i.e., before there were any mosquitoes at all-providing the infection had occurred in that year." "As 24-36
development
The seasonal incidence and the great preponderance of cases show that most of the patients must have been infected the previous year while in military service elsewhere. Further, the geographical incidence in many cases was too disconnected for infection to have arisen where the malaria developed ; and in some districts the summer temperature was too low to permit infection by mosquito bites that year. The view that infection came from hibernating mosquitoes is put out of court by the appearance of malaria in districts which had been free the year before. A questionary sent to 868 patients showed that all but 13 of the 596 who replied had been in military service the previous year in the
military
Christophers, S. R. British Encyclopædia of Medical Practice, London, 1938, vol. VIII, p. 304. 2. Hernberg, C. A. Acta med. scand. 1947, 127, 342. 3. Swellengrebel. N. H., De Buck, A. Malaria in the Netherlands, London, 1938 ; see also Lancet, 1938, ii, 894. 1.
729 Karelian Isthmus, where there had then been much malaria,. The possibility of an epidemic of benign tertian malaria in England owing to the return of soldiers treated with mepacrine has already been discussed in these columns. In the Finnish cases the incubationperiod must have been 6-14 months, unless the cases A long winter incubation in man is not were relapses. likely to arise in cases of malaria developing in England, where the temperature lies well within the thermal boundaries of endemic malaria. CARE OF THE AGED IN DENMARK
DENMARK was the first country to introduce the of free provision for the old. In his address to the International Conference of Physicians on Sept. 9 Dr. Johs. Frandsen noted that the Danish Old Age Relief Act of 1891 differentiated clearly between support in old age and help to the poor, though the extent of relief to the old was left to the discretion of local authorities. In 1922, however, the last flavour of poorlaw was removed from the Act, and " old-age relief became the old-age pension. It is paid to men over 65 and women over 60 whose income is below a prescribed level, provided they have a clean police record for the previous five years and have not lived lives offensive to public morals ; presumably those whofail in these respects are relieved in other ways. The amount of the pension is a basic sum calculated on the cost of living in the capital, the provincial towns, and the country districts. Thus a married couple receive about f1l5 a year in Copenhagen, JE98 in provincial towns, and f83 in country areas ; this amounts to about 46% of the average net income of an unskilled worker. The sum varies with the cost of living, and there are various supplements-for example, a children’s allowance for those who are responsible for children under the age of 17, fuel and clothing supplements, and a personal supplement for those with special difficulties. Of Denmark’s 4 million inhabitants some 200,000 are at present drawing the pension. As in England, there are both voluntary and municipal homes for the old. The council homes are exclusively for pensioners, the pensions being paid to the homes with the proviso that the old people are to live under conditions as good as they could buy with their pensions elsewhere. Entrance to the homes is voluntary, and the old people usually take their own furniture in with them ; they can prepare meals in a common kitchen, and suitable interests and occupations are provided. Most of the voluntary homes were founded before legislation for the old was introduced. Though small properly equipped flats are the most suitable homes for old people living alone, they are expensive to provide, and the Danish housing problem is as acute as our own. There are, however, some blocks of flats for old people, built by the local authorities before the war. A woman inspector lives in each block to help and look after the old people, and in many of the blocks there are assembly rooms for concerts and celebrations. In 1942 there was accommodation, in voluntary and municipal homes and in flats, for some 25,000 old-age pensioners throughout the country. In Copenhagen most of them are housed in flats ; but it is estimated that 285 "places" per 1000 pensioners are needed in Copenhagen ; while in other towns the figure is put at 250, and in rural areas at 200 per 1000. Most of the homes have a sick-bay, and the largest of them has a hospital with a full-time medical officer. In other homes the old people can choose their own doctor, but if they have no preference they are attended by one appointed by the local authority.
principle
4. Lancet,
1945, ii, 49.
"THEY ORDER THIS MATTER FRANCE"
BETTER IN
THE tendency in France to elevate therapeutics into art in its own right has led at times to a finical refinement ill suited to crowded evening surgeries. Perhaps we in this country have erred in a contrary sense in guiding our treatment by its apparent effect on the patient, without much theoretical consideration of the modus operandi of the remedy. In the case of penicillin the charge of pragmatism will not lie against us ; but it is interesting to note the methods of our French colleagues in handling a drug of which our experience is somewhat longer than theirs. A paper by Mollaret1 on guiding principles in the use of antibiotics makes three major suggestions. The first is that, so far from decreasing as treatment proceeds, the dose should be maintained at its original high level; by this means he hopes to discourage the organism from becoming penicillin-resistant. (We doubt if, in this country, penicillin dosage is often arranged on a decreasing scale, since it is recognised by most users that a drug so rapidly excreted can be kept at optimum levels only by continuous or repeated dosage-in contrast to sulphonamide therapy, for example, where a large initial dose allows a high concentration to be built up which may be maintained by subsequent smaller doses.) His second suggestion is that the final dose should be double that administered previously, so that it shall give the coup-degrace to any organism that still resists. Since the concentration in the tissues is usually in excess of that required to deal with the organisms, the advantage of this procedure is questionable ; but certainly nothing is lost by it beyond a few hundred thousand units of penicillin. Thirdly, and most ingeniously, he suggests that by giving penicillinase after the last dose of penicillin it may be possible to avoid creating a residue of drugfast organisms at the end of treatment. This, however, seems to be a case of pursuing logic altogether too far. That strains of organisms exposed in vitro for many generations to sublethal concentrations of penicillin may become resistant to penicillin nobody doubts ; but that this resistance will develop in the few hours while the last remnants of a therapeutic dose are being excreted from the body seems most unlikely. In fact resistance to penicillin seems to develop only rarely under therapeutic conditions, and may best be avoided by attention to Mollaret’s first suggestion. Though the last words on the administration of penicillin have yet to be said, we do not yet see reason to echo here the dictum of the Rev. L. Sterne. an
DEATH ON THE ROAD METHODS of reducing road accidents still need much study. Mr. J. S. Dean, in a recent book,2 makes some interesting and meritorious suggestions for reducing these accidents. The installation of governors on vehicles subjected to a general speed-limit would doubtless be beneficial, though the manufacture of any mechanical device presents difficulties at the present moment. Footpaths beside all roads are also desirable, but the arrears of road maintenance which piled up during the war years will use up most of the money available for the improvement of highways for a considerable time to Mr. Dean notes that in 1937 private cars were come. involved in 33-2% of the total road accidents, public conveyances in 6-8%, and commercial vehicles in 14-3% ; and he concludes that private cars have the worst accident record. This hardly tallies, however, with the car-mileages he gives for these different types of vehicles, which have the ratios of 14-40 : 3-04 : 7-18. Private 1. Mollaret, P. Bull. Soc. méd. Hôp. Paris, 1947, 63, 643. 2. Murder Most Foul. A study of the road deaths problem. London : Published for the Public Affairs News Service by George Allen & Unwin. 1947. Pp. 114. 3s. 6d.