In the typical cases of Tomaselli, Murri, Vincenzi, and others the idiosyncrasy against quinin was preserved for a very long time, even months and years, and could be demonstrated at any moment. Tomaselli observed only isolated cases in which the idiosyncrasy disappeared, and then only a long time after the last malarial infection and after the patients had removed to a region free from malaria . And in these cases it recurred with a new infection.

Murri's case was able to stand, after a year's interval, doses of quinin from 0.10 to 0.50. After its administration there occurred fever, associated with albumin, peptone, and propeptone in the urine, but no hemoglobinuria. Grocco brought his case so far that it could eventually stand large doses (even to 1.5 gm.) subcutaneously, yet on counting the red blood corpuscles, he always found a cythemolysis, and Vincenzi saw this same case one and one half years later, when 0.10 quinin would again produce paroxysms.

The paroxysms take place from one to six hours after administration of the quinin. Tomaselli described them as follows: "While rejoicing in perfect health, the patient is suddenly seized by nausea, restlessness, and convulsive twitchings. The skin becomes cool; the pulse small, rapid, and scarcely palpable; the face blanched and accompanied by an expression of suffering. The patient is possessed by a deadly anxiety and not rarely a repugnance to quinin. He complains of pain in the lumbar region, sometimes associated with an internal burning. Thirty minutes to two hours after this stage the temperature rapidly rises to 39° to 41°, according to the severity of the paroxysm. Profuse bilious vomiting sets in; sometimes a serous bilious diarrhea. Urination becomes imperative, and with frequent intermissions a large quantity of blood stained urine is passed. Salivation, dyspnea, jaundice, severe depression, lipothymia quickly follow. These phenomena usually occur so suddenly that the paroxysm might be termed fulminating, though sometimes this condition is ushered in by a feeling of restlessness, lasting from a few minutes to an hour, which the patient is unable to explain.

"The duration of the fever is variable, depending somewhat on its height. In the majority of cases, after twelve to twenty four hours, seldom longer, a sudden or gradual fall of temperature takes place, and with it disappear all the symptoms with the exception of the jaundice, which often persists for a short time."

Deviations from this course in one or another direction may occur, yet, taken altogether, the syndrome is pretty constant.

The 'condition of the blood and the urine is the same as that in hemorrhagic pernicious fever. Grocco found the blood serum in his case stained red, though shadow corpuscles were wanting. The iso tonicity of the blood was normal. In the urine he found hemoglobin, methemoglobin, large amounts of urobilin, peptone, and propeptone, but a diminution in the phosphates. In mild cases the hemoglobin and albumin were wanting, urobilin only being present.

The duration of the quinin paroxysm is usually shorter than that of true blackwater fever. As soon as the organism gets rid of the quinin the paroxysm ceases (Tomaselli). Paroxysms may be produced by all the preparations of quinin, even when applied locally. The doses which are sufficient are often astonishingly small. Tomaselli saw a case in which 5 centigrams produced the effect.

The hemoglobinuria occurs whether or not a malarial infection exists at the time. Grocco's conjecture, therefore, that we have to do in these cases with a poison excreted by the malarial parasites under the irritation of quinin, is scarcely likely, since to support it we would have to assume that in a number of cases the parasites were concealed in the parenchymatous organs.

It is worthy of remark that quinin, when exhibited in a case of acute malaria , sometimes produces its therapeutic effect, with, simultaneously, a paroxysm of hemoglobinuria. In these cases, therefore, quinin is at the same time beneficial and injurious.

Moreover, the noxious effect may predominate. Tomaselli observed several cases in which complete anuria occurred, followed several days later by uremic symptoms and death. (For the treatment of quinin hemoglobinuria see section on Therapy.)

From what has been stated, therefore, a diagnosis of quinin hemoglobinuria may be made if a paroxysm of hemoglobinuria can be produced every time by the exhibition of quinin (at least, for a period of several months), whether or not malarial parasites happen to be present.

The diagnosis is aided by the patient's history of previous infections and the effect of quinin, to which his attention may have been attracted. The differential diagnosis between quinin poisoning and blackwater fever depends on the principles enunciated on page 322. Still, we may say that no conclusion is to be drawn from a paroxysm occurring after one administration, but only when this effect is repeatedly produced by the smallest doses, both during and apart from an infection.

Amyloid Degeneration

The occurrence of amyloid degeneration after malaria was demonstrated by Rokitansky. Later experience has shown, however, that it is among the rarities. Budd asserts that he never encountered it, and Frerichs reports only two cases. In Fehr's statistics of 145 cases of amyloid degeneration 4 figure as malarial. In Rosenstein's

43 cases, 4 were after malaria . Axel Key found it repeatedly in the renal vessels. According to Kjelt, it is not rare in Finland after malaria.

Laveran mentions, among his own observations, two cases of amyloid, though both of these were complicated with chronic bronchitis and bronchiectasis. Kelsch and Kiener saw no case. In their work they give only an observation of Grasset's.