A Medical Research Council report by DIXON and a study of 450 cases, the great who had served in India. These soldiers majority being workers have tried to estimate the frequency of the disease in such patients; and, on the basis of the number of patients apparently infected between 1921 and 1937 and of the figures for British soldiers and airmen serving in India during this period, they conclude that clinical evidence of the disease occurred in between 1-2 and 2-0 per 1000. They note that of the troops who served in or passed through India in the late war, only 45 are known to have contracted cysticercosis. Of the proved cases 21-6% had a history of an intestinal tapeworm, which is approximately eight times the frequency in the population from which the patients were drawn. DIXON and LIPSCOMB found considerable difficulty in estimating the time between infection and the inset of symptoms except in a few cases; but when they arbitrarily selected the midpoint of a man’s service in India as the time of infection they found that symptoms might start one to thirty years after infection, the average being about four and a half years. In 83% of patients symptoms started within seven years of infection-which is distinctly encouraging for those who served in India during the war, as it seems unlikely that they will now develop the disease. As was to be expected, the commonest neurological manifestation proved to be epilepsy, which occurred in 92% and was the only symptom in 31%; the epilepsy may be of any type, and indeed it is rather characteristic for more than one type to occur in a single patient. Other neurological disorders may arise, often in combination with epilepsy; of the 450 patients, 13 had focal neurological signs, most commonly hemiparesis, and 1 had progressive tetraparesis and at operation was found to have cysticercosis in the cervical enlargement of the spinal cord. In 29% intracranial hypertension developed. This fell into three distinct clinical groups. In the first it developed fairly soon after infection and was associated with fever. In the second it occurred later in the course of the disease, in association with epilepsy. Of 14 patients in this group 2 recovered without operation and 6 recovered after operation; postmortem examination in the fatal cases apparently showed multiple intracerebral cysticercosis but no evidence of obstruction of the cerebrospinalfluid pathways, and the reason for the intracranial hypertension seems uncertain. In the third group there was obstructive hydrocephalus due to a racemose cysticercus or a single cyst or arachnoid adhesions associated with a cyst. In this group the prognosis seems to be very poor even after operation, for, of the 9 patients, 8 died within three years; the 9th improved for a time but then relapsed and was finally killed in an accident. Mental symptoms occurred in 39 patients. In 19 of these there was organic mental deterioration;
LIPSCOMB 11 describes
5 had progressive dementia, while 11 had a severe affective disorder, but in these patients the relation between the cysticercosis and the psychiatric disorder was
21. Dixon, H. B. F., Lipscomb, F. M. Spec. Lond. 1961, no. 299. Pp. 58. 6s. 8d.
Rep. Ser. med. Res. Coun.,
DIXON and LIPSCOMB consider in detail the subcuticular nodules which are so characteristic of the disease and which, by providing material for biopsy, are most important for diagnosis. These nodules are primarily in the muscles and appear when the larvar die and the fluid content of the cysts increases. They commonly vary in size from time to time, and thorough inspection and palpation of the whole body may be needed to find them. They were detected in 54% of the series. They are often the first sign, or they may appear at about the same time as epilepsy develops. New ones may continue to appear for months or years after their first appearance. In only occasional cases is muscle pain complained of; but in extremely uncommon cases where the muscles are massively invaded, there may be pain with swelling and weakness of the muscles re-
sembling a myopathy or myositis.22 23 The most certain method of diagnosis is by biopsy and histological examination of a nodule, but many cases have been diagnosed by radiographic examination of the muscles. The cysts in the muscles usually become calcified within about five years of infection; but there are many exceptions, and in 3 patients cysts were only seen after nineteen years. Calcification of the intracranial cysts is much more rare, and, when it does take place, the cysts appear as small rounded opacities and do not have the elliptical shape so characteristic of the muscle cysts. Of the 256 cases where X-rays of skull and muscles were available, there was only 1 where calcification in cysts could be seen in the brain and not in the muscles. The 450 patients were followed up till the end of 1958, when 42 had died of the disease, 5 had died partly from the disease, and 47 had died from other disorders. The commonest causes of death from cysticercosis were status epilepticus and intracranial hypertension. DIXON and LiPSCOMB found that in many cases fits could be controlled by anticonvulsant drugs, and that the prognosis for those with epilepsy was less unfavourable than had previously been supposed. Surgical removal of cysts for the relief of focal epilepsy was seldom of value. In the treatment of intracranial hypertension without obstructive hydrocephalus, decompression might be helpful; but the results of operative treatment of obstructive hydrocephalus had been disappointing.
Drug Addiction THE interdepartmental committee appointed, under Sir RussELL BRAIN’S chairmanship, to review drug addiction in this country has now reported.24 Since 1926 when the Rolleston committee reported on morphine and heroin addiction many new drugs liable to produce addiction or to be habit-forming have been introduced. After careful examination the committee concluded that the prevalence of addiction to dangerous drugs-both the older ones such as morphine and heroin and the newer synthetic agents such as pethidine and methodone 22. 23. 24.
McRobert, G. R. Indian med. Gaz. 1944, 79, 399. McGill, R. G. Indian J. Med. Surg. 1947, 1, 109. Ministry of Health, Department of Health for Scotland. Drug Addiction. Report of the Interdepartmental Committee. H.M. Stationery Office: 1961.
still very small. While there is no official register of addicts, the arrangements of the Government Departments concerned ensure that nearly all addicts are known. There is no evidence that any definite increase is taking place. Doctors and nurses still form a disproportionately high fraction of all addicts. Successful treatment of drug addiction is possible only in a suitable institution-preferably the psychiatric ward of a general hospital. Addiction being so rare in this country, few doctors here have had any experience of it; and the report includes a useful appendix on treatment, based on advice from America. Gradual withdrawal of the drug is advocated. The main problem is the longterm management of the patient after discharge from hospital, when careful supervision and guidance are essential. Detailed information about the ultimate prognosis is lacking, but the impression is that final results are disappointing. The committee makes some " interesting comments on stabilised addicts ". Whether such people exist has been doubted, but the committee found that there were a few taking small, regular doses of dangerous drugs and leading reasonably satisfactory lives, though they were unable to abandon the habit. Such cases have in the past given rise to some misunderstanding. There is no official allowance of dangerous drugs for them, and they are treated solely as patients under the care of their own doctor. This arrangement has worked well, but clearly there is a possible loophole for abuse. Fortunately no new statutory tribunals or other powers are regarded as necessary, but the committee recommends strongly that every doctor should obtain a second medical opinion in writing before embarking on the regular prescribing of a dangerous drug either to a patient, to a relative,-or to himself for a lengthy periodsay, in excess of three months. This should not of course interfere with the management of painful terminal illness. The committee endorses the important advice that, in the absence of a letter from the patient’s own doctor, a doctor should give only a limited supply of a dangerous drug to a patient temporarily under his care. The committee’s comments on the numerous new drugs affecting the central nervous system are of great interest. It points out that all potent analgesics are likely to be addictive. It does not insist on official clinical trials of new analgesic drugs before they are marketed; but it declares that no drug likely to be addictive should be released by the manufacturers until it has been carefully tested for this possibility (the committee does not suggest how this should be done). There has undoubtedly been a large increase in the use of drugs which depress the central nervous system. Between 1951 and 1959 the quantity of barbiturates prescribed annually almost doubled. An analysis showed that barbiturates, other hypnotics and sedatives, and analgesics and antipyretics (excluding dangerous drugs) accounted for about 19% of all prescriptions issued in the National Health Service. No figures for tranquillisers were available, but there can be little doubt that they have been increasingly widely prescribed. It has also become more generally appreciated that addiction and habituation to stimulant drugs such as amphetamine and phenmetrazine
definite information is available about this happens. In 1959 there were some commonly 5,600,000 N.H.S. prescriptions-about 2-5% of the total-for preparations of the amphetamines and phenmetrazine. This amount of prescribing may possibly be regarded as excessive; but the general impression is that, though serious cases of addiction may arise, such abuse is can
widespread. drugs affecting the central nervous system are potentially habit-forming, but they are undeniably potent therapeutic agents and of great value in psychiatry. The position certainly needs careful watching; and there is need for operational research into their prescription throughout this country. It is important to ensure that in future new drugs acting on the central nervous system and regarded as liable to produce addiction or habituation are restricted to supply on prescription. No further statutory control is at present thought advisable. not
Annotations CONTRACTS FOR PATENTED DRUGS
under the Patent Acts gives an exclusive of manufacture to the patent holder and to such other persons as he may choose to license on such terms as he thinks fit. The Courts will, if called on to do so, grant an injunction to restrain any person within the United Kingdom from infringing the rights of the patent holder. The patentee’s rights are enforceable against the Crown except that under section 46 of the Patents Act, 1949, a Minister can sanction the use of a patented invention by any person provided it is required for the services of the Crown and proper compensation is paid to the patentee. It is section 46 that the Government (see p. 1176) has invoked in connection with certain drugs for the hospital service. The Ministry of Health explains that certain patented drugs from what are believed to be unlicensed sources abroad have been offered to hospitals at prices much below those ruling in this country. Hospital authorities are now instructed not to buy patented drugs from unlicensed sources. Instead, the Government will invite tenders by advertisement for the supply of drugs under central contracts, and both British manufacturers and importers will be able to tender. Compensation to patentees will be negotiated by the Ministry, and if agreement cannot be reached the terms will be settled by the High Court under section 48 of the Act of 1949. The new procedure will not apply to the supply of A
patented drugs to the general pharmaceutical services, which are not regarded as Crown services for this purpose. Nor will it apply to all patented drugs used by the hospital service; for the moment it will apply, in the words of the Ministry statement, to certain widely used drugs such as the tetracyclines, choloramphenicol, and chlorothiazides ". In selecting drugs for action under section 46, the Ministry says that it will take into account such matters as the length of time a drug has been on the market, the quantities and sums involved, and the potential scope for saving. " The importance of patent protection for the development of the British Pharmaceutical Industry and for the encouragement of research is fully "