751 Treatment of Malaria. No essential change has been introduced in antimalarial treatment. The opinions expressed and the different methods proposed are summarised below. Quinine treatment.-In the treatment of malaria the points to be considered are the method of administration of quinine, the time of administration, and the dosage. As to the method of administration, quinine may be given intravenously, intramuscularly, and by the mouth. The method of int’l’aven0168 injection is generally regarded Its dangers as a procedure only for exceptional cases. appear to have been exaggerated, and the technique recommended by Jeanselme and Manaud,15 consisting in the slow injection by a serum syringe of 1 g. of quinine bichlorhydrate dissolved in 100 g. of saline, appears capable of completely removing such dangers. Carnot and de Kerdrel have shown that the intravenous method is the method of choice in dangerous malignant attacks. On the other hand, this method is not superior to the others in its sterilising power, doubtless on account of the rapidity of elimination of quinine introduced directly into the circulation. The indications for its use are, therefore, special and precise. The general use of int’1’amusmÛa;r injections has brought to light a certain number of difficulties. Even when it does not produce abscesses, which have, in fact, been fairly frequent and often severe, the caustic action of the quinine is painful. Although, however, this method should not be employed as a routine, nevertheless it is indicated as the only one practicable for patients with gastric irritability who are the subjects of malignant attacks. Many writers give preference to administration by the mouta. Reference must be made to the opinion held by Marchoux as to the value of giving the least soluble forms of quinine, their efficiency being the greater because they are eliminated more slowly; the sulphate, and, above all, the alkaloid itself, being more active than the other salts. According to Marchoux, chronic malaria must be treated by oral administration. The effective dose of quinine was generally fixed at 1 g. per day for constant treatment. A majority, however, of the medical officers (Soulie, Gutman1G) advise a dose of 2 g., especially in infections due to the parasite of malignant tertian fever; some even advocate a dose of 3 g. for two or three days. The time of administration of quinine appears to have lost much of the importance imputed to it at a period when it was sought to make the absorption of the drug coincide with the presence in the peripheral circulation of the young parasites This end cannot be which are alone susceptible to it. attained in those cases in which the fever is continuous from the onset, as the successive generations of parasites The same is true at the stage when the are too numerous. paroxysms become so irregular that it is difficult in practice to administer the drug at the proper moment. The methods employed vary according as the case is one of primary fever, or of attacks at the so-called secondary stage of malaria. At the onset, when the aim is to sterilise the patients by preventing the appearance of the resistant forms, the gametes, it has been usual to adopt the classic method of administering quinine in large and continued doses. Mention should, however, be made of the technique employed by Abrami, who prefers to administer the quinine in very large doses at the febrile periods only, in order to destroy in succession the generations of parasites passing into the circulation. In secondary malaria comparatively little use appears to have been made of the method of discontinuous dosage, based on the weekly periodicity of the recurrences. The method chiefly adopted has been that advocated by Ravaut by which two days’ treatment with 1 or 2 g. of quinine a day is alternated with two days of injections with strong doses of cacodylate. Castaigne and Paillard give 2 g. of quinine a day for three days each week. These methods of treatment have the disadvantage of working in the dark. For this reason the method advocated by Marchoux 17 is of the greatest interest. It is based on the observation that the parasites pass into the blood15 Jeanselme and Manaud: Injections Intraveineuses de Quinine, Presse Médicale, March 31st, 1917 ; and Carnot and de Kerdrel: Paris
Médical, 1917, No.
1. 16 Gutman: Presse Médicale, March 10th, 1917. Marchoux : Le Paludisme de Salonique, Bull. Acad. de Médecine, August 3rd, 1917. 17
stream two or three days before the rigor, the delay being due to the need for their multiplication to an extent sufficient to provoke the rigor. With regular examination of the blood at intervals of three or four days it is possible to administer the quinine at the right moment and to destroy the generations of parasites in succession as they appear in the circulation. Not only can the recurrence of rigors be anticipated, but the patients can also be rendered sterile with a minimal expenditure of quinine. Marchoux considers that the destruction of four generations of parasites would suffice to sterilise the system. Accessory treatment.-In association with quinine, iron and arsenic are the standard drugs for the treatment of malaria. Medication with arsenic has been specially studied, and many writers recommend its systematic use. In France the combined arsenic-quinine treatment advocated by Ravaut, Reniac, and de Kerdrel18 is specially popular. On two successive days 0 20 to 0’30 g. of arrhenal are injected, followed on the next two days by 2 g. of quinine chlorhydrate by the mouth. This treatment gives excellent results, and has in all cases a remarkable effect on the general health. Carnot 19 has made a general study of arsenical medication in malaria. He avoids the use of atoxyl and gives preference to injections of arsenobenzol. The lesions of the suprarenal glands noted in malaria justify the use of adrenalin intravenously or subcutaneously, particularly during the rigors and in weak and unstrung subjects, and especially at the commencement of infection. Ravaut, who finds frequent evidence of suprarenal insufficiency in secondary malaria, agrees with Perrin and Edelmann 2° in advising the use of adrenalin at this stage. From the aggregate of the studies published on the therapeutics of malaria there emerges the conclusion that no method of treatment is capable of producing within a short period permanent sterilisation of the patient. Three methods of treatment deserve mention by reason of their originality or of the results obtained :1. Abrami 21 treats the complications of primary malaria by quinine in very large doses-3 g. of quinine daily, preferably by injection and in two doses, until the temperature no longer exceeds 100-4° F. ; the daily dose is then diminished to 2 g. by injection, and is continued until the second day after the temperature has reached the normal. The originality of the method consists in the fact that the quinine is not given during the period of apyrexia, but that the sterilisation is effected by successive doses at the onset of a paroxysm. 2. Ravaut and Carnot have recommended treatment with arsenic. Ravaut alternates the injection of 2 g. of quinine a day for two days with the injection of 0-20 to 030g. of arrhenal for a further two days. This course is followed for one month, and if necessary renewed for three weeks longer after an interval of ten days. Carnot gives six injections of arsenobenzol in a month at the rate of one dose of 0 ’30 to 0 ’45 g. every five days, and then gives a protective dose of 0’45 g. once a fortnight, then once a month. 3. Marchoux makes a practice of examining thick bloodfilms twice a week ; in the case of malignant tertian fever and during active stages on alternate days. If the result is positive 1 g. of the alkaloid is given at once. It is extremely rare for an attack to develop between two examinations. These examinations are carried out in a dispensary at which the patients attend regularly. By this method it is possible to employ them on active work during the whole course of treatment. .
DISTRIBUTION OF SOLDIERS, TEMPORARILY UNFIT THROUGH MALARIA, IN AGRICULTURAL COLONIES. BY PROFESSOR E. JEANSELME. THE malaria of the East is a most obstinate disease which resists the most energetic treatment for many months. If the convalescent is returned too quickly to his unit he has a relapse which makes it necessary to readmit him to hospital,
18 Ravaut, Réniac, de Kerdrel: Le Paludisme d’Orient Marseille, Presse Médicale, August 16th, 1917. 21
ou
de
19 Carnot: Paris Médical. Nov. 3rd, 1917. 20 Perrin and Edelmann: Paris Médical., Sept 21st, 1918. Abrami: Le paludisme primaire en Macédoine, Presse Médicale,
March 22nd, 1917.
.
752 substance which should be easily recoverable in the urine. We chose methylene-blue. Other authors have made use of other substances. The red colouration of phenol-phthalein, which presents certain advantages, has recently been much used in America. The substance may change ; the principle and the significance of the test remain unaltered. In place of foreign substances certain authors have proposed to make use of the normal contents of the urine for their
But so that he passes from one hospital system to another. this semi-invalid, immured between the four walls of a hospital ward, droops before one’s eyes under the spell of depression and of lack of occupation. If an attempt is made to vary the treatment by allowing him frequent leave from hospital, another difficulty appears. When once he has crossed the threshold of the hospital he does not know where to go or what to do. Then he is assailed by unhealthy temptations ; there are numerous public houses to visit, or worse still. He uses every possible means of getting leave again, for a moral disease, idleness, now aggravates the physical malady. To master this is to give him back his gaiety and his confidence in the future. To get this result it is sufficient to put the malarial patient back to the land, as is shown most con-
investigation.
clusively by actual experience. My method is as follows for the malarial patients in the Hopital du Pantheon, of whom I am in special charge. All the convalescents who show some aptitude for agricultural work are handed over to contractors who are developing groups of abandoned farms. Naturally the results depend on the care taken in the choice of men. It is only by personal inspection that the doctor can ascertain the demands which will be made on his
I
patients. The distribution of malarial patients in agricultural centres differs entirely from leave given for agricultural work. The latter is an individual measure which disperses men haphazard and leaves them to themselves, so that they escape military and medical observation. The measure here suggested is, on the contrary, collective ; the malarial soldiers, formed into units, work under the supervision of officers. It is possible for the doctor to superintend their health and to ascertain, before establishing a centre, that there are in the district no nests of anopheles to spread the disease. To summarise : The distribution in agricultural colonies of malarial soldiers temporarily unfit for military service is the surest means of hastening their return to health and of giving to the soil the labour which it so urgently needs.1 The same principles have been applied by Dr. Gavin, the medical officer in command of the hospital for malarial patients at Modane (height, 1050 metres). As the mountainous country of the Haute-Maurienne does not lend itself to extensive cultivation the patients are divided by twos and threes among the inhabitants. They come down twice a week for medical examination. While they share meals with the farmer and are lodged comfortably in chalets, they work on an average from five to six hours a day and receive a daily wage of 3, 4, and even 5 francs. The results have been exceedingly satisfactory-all the pastures of the upper valleys (at an altitude of 1500 to 2000 metres), which it had not been possible to reap during the previous years, were dealt with successfully this year.2 M. Justin Godart, Under Secretary of State for the Ministry of Health, as a result of his experience of these results, has referred as follows, in Circular No. 626/7 of Nov. 25th, 1917, to the work of temporarily unfit malarial soldiers :’ In the course of his hospital treatment the patient, in cases and at stages decided always by his medical officer,
may be allotted moderate work, either in the hospital or in the gardens or grounds belonging to the unit; or he may be placed at the disposal of neighbouring farmers for a wagethe ideal method-or may even work in industrial establishments or factories, on the strict understanding that the work is subject to certain general provisions as to general hygiene and hours of labour, carefully adjusted to the stage of convalescence of the patient. In every case these various activities must always be compatible with medical supervision and with the needs of controlled treatment."
REVIEW. CHARLES ACHARD. Professor By Thesis by on Renal -Function in Chronie Nephritis. PASTEUR-VALLERY-RADOT. Paris : Masson et Cie. 1918. Pp. 256. Fr.10. THE investigation of renal activity by clinical methods is a comparatively new proceeding. It was in 1897 that, with Castaigne, I proposed’a method which consisted in the introduction into the organism of measured doses of a foreign
Studies
1 Extract from
July 10th, 1917.
.
a
communication to the
2 Extract from the Progrès de Lyon, letter from Dr Gravin, Dec. 15th, 1917.
Academy of Medicine,
Sept. 30th, 1917,
and from
With Paisseau I introduced, in 1904, the induced azoturia we added 20 g. of urea to the fixed diet of our subjects. By this means we discovered that the elimination of methylene-blue and urea was nearly parallel. We showed also that in the case of renal impermeability the quantity of urea in the blood rises, and that this quantity may be decreased by a diet which is poor in nitrogen. Professor Widal and his pupils have carefully studied this urea retention ; they have shown the clinical interest of the percentage of urea in the blood and its value in the prognosis of uraemia. Afterwards, Ambard discovered the mathematical formula governing the physiological secretion of the and deduced from it the method of calculating that kidney " constant"which enables us to estimate the functional efficiency of the kidney from the secretion of urea. As for the elimination of sodium chloride, that also, according to Ambard, is subject to a law and a formula. It is possible, moreover, to discover whether the sodium chloride is being well eliminated by an induced chlorinuria test. But I do not believe that the retention of sodium chloride in the organism depends solely on renal imperfection ; I think that extra-renal causes often intervene. The retention of this salt in the organism is never accompanied by an increase of sodium chloride in the blood, for, when it is not eliminated it is diffused in the tissues and fluids of the organism and attracts to itself water, with the result that its dilution reaches much the same percentage as in the normal state. Widal has laid great stress on the effect of this retention in the production of dropsy. In his thesis Pasteur Vallery-Radot recalls the work which I have just mentioned and the different methods of renal exploration. He classifies the symptomatology of the nephritides, in accordance with the ideas developed by Widal, into several syndromes: the hydrochloric retention syndrome, the urea retention syndrome, the arterial hypertension syndrome, the urinary syndrome (albuminuria, cylindruria, leucocyturia). He criticises, in the course of his exposition, certain new methods of renal exploration suggested in Germany by Schlayer, the object of which is to distinguish the activity of the glomeruli from that of the convoluted tubules by comparing the rate of elimination of potassium iodide and lactose. Pasteur Vallery-Radot has tried these methods and has only obtained inaccurate results. The study on the elimination of sodium chloride is one of the most personal chapters in this work. In order accurately to determine chlorine elimination in the nephritides it is necessary, according to the author, to put the patient at first upon a salt-free diet, then to give him 15 g. of sodium chloride daily and to estimate the chlorine excreted in the urine. In the normal subject it takes three days to establish chlorine equilibrium (elimination equal to ingestion). But when there is chlorine retention a longer time is necessary; during this period the patient’s weight increases and oedema, may become apparent. (This succession of events occurs similarly with other substances when they are retained. I have shown, with Clerc in 1900, that it is true of methyleneblue in the case of renal sclerosis, in which there is impermeability to the blue.) In a chapter devoted to urea retention the author examines the value of urasmia in prognosis. He indicates also the influence of the chlorination of the organism, which may reduce temporarily the percentage of urea in the blood. For the investigation of the secretion of urea he favours Ambard’s constant and the phenol-phthalein procedure. Permanent arterial hypertension is always, according to him, caused by a nephritis that may be revealed by an examination of thkidney function. The last part of this work is devoted to experiments made on rabbits which had been fed with milk povader. This diet, as has been already shown by Martin and Pettit, produces nephritis in the rabbit. Pasteur Vallery-Radot has studied this nephritis and has induced retention of urea in these animals.
test, in which
a,