NONSPECIFIC PROTEIN THERAPY
The treatment by nonspecific methods in a series of cases of influenzal pneumonia has been the subject of two recent papers.[295] These methods are a development of the work of Ichikawa, Kraus, Lüdke, Jobling and Petersen, and others on the treatment of typhoid fever and of Miller and Lusk’s work on arthritis. In the original work in this field it was recognized that there were certain inherent dangers in the method and that wide application would be permissible only with the greatest caution and under careful control.
When vaccines and other toxic protein substances are injected intravenously a train of reactions takes place that includes: (a) a primary leukopenia, followed by a leukocytosis; (b) a primary lessening of the coagulability of the blood, followed after some interval by a reduction of the coagulation time; (c) a pronounced lymphagogue effect, the flow of lymph from the thoracic duct being increased threefold; (d) a hyperperistalsis of the intestinal tract, and (e) a marked splanchnic engorgement with a resulting lowering of the systemic blood pressure. The alteration of the coagulability of the blood, together with the vascular engorgement of the splanchnic area and the coincident increase in motility of the intestinal tract that follow the therapeutic injection, all tend to increase the possibility of intestinal hemorrhage. Protein therapy is therefore not a safe procedure in this particular disease. That we are able to terminate a certain number of cases of typhoid fever by crisis by means of such injections is of very great interest from a theoretical point of view.
In the treatment of arthritis, the results seem much more satisfactory. The work of Miller and Lusk[296] has been confirmed by a number of observers, among them Culver, Cecil, Snyder, Cowie and Calhoun; and there seems little doubt that we may be able to give prompt relief and even permanent freedom from symptoms in a considerable percentage of cases of acute and subacute arthritis, especially those classed as of rheumatic origin—and this with practically no risk to the patient.
As with other new therapeutic measures, there is still some uncertainty as to the proper dosage, which is a matter of considerable importance, in order to arrive at a just estimate of the relative advantage or danger in the treatment. Typhoid vaccines have been extensively used because they are readily procured and give a prompt and sharp reaction. However, they have the disadvantage of inexactitude in the bacterial count, as well as being of varying degrees of toxicity, the latter factor depending not only on the use of different strains of bacteria in their preparation but on the age of the vaccine. Synder,[297] as well as other workers, is of the opinion that the primary dose should be small—from five to ten million organisms—and that the dose of typhoid bacilli injected should never exceed two hundred and fifty million. While a sharp reaction on the part of the patient is apparently a desideratum, a sufficient response can usually be elicited with a relatively small dose. There is no object in subjecting the patient to the risk of the profound depression that follows occasionally in the wake of large doses. Indeed, the only serious results so far ascribed as due to this form of therapy have followed very large doses or the use of relatively large doses in moribund patients; or such unreasonable procedures as the intravenous injection of milk. It is true that milk injections were recommended by some of the German investigators, but they were always used intramuscularly.
In the treatment of pneumonia, Roberts and Cary[298] have employed a vaccine made up of 100 million of each of the following organisms per cubic centimeter: influenza bacilli, pneumococci, staphylococci and streptococci. Of this vaccine they injected, intravenously, first 0.5 c.c., later 1 c.c. In the series of 200 patients so treated there was no evidence of injury to the patients in any way. The mortality in this series was 9.5 per cent.; in a series of eighty-six patients not treated with vaccine, the mortality was 31.2 per cent. In the untreated series, 20 per cent. recovered by crisis; in the treated, 36 per cent. so recovered. Before any reliance is placed on such statistics they should be analyzed and compared carefully according to age periods, as the death rate may vary at different ages. Cowie and Beaven[298] used typhoid vaccine in the treatment of their patients, and they consider the vaccine shock as indicated only in the early stages of pneumonia.
Before applying the treatment to such diseases as pneumonia it would seem that prudence would demand a thorough familiarity with the range of the reaction and the degree of toxicity of the preparation it is intended to use by first employing it in some arthritic cases. In pneumonia we must ever keep before us the vital factor of cardiac impairment; and certainly we must not undertake any measure that may depress the function of the heart. In arthritis this danger is largely a negligible one; and, with proper precaution, nonspecific therapy is not only without risk but indeed frequently followed by gratifying clinical improvement. Only in the light of experience gained in the manner indicated would it seem permissible for us to attempt to extend this form of therapy to more acute infections.—(Editorial from The Journal A. M. A., May 17, 1919.)