are borne out, viz., brain weights with psychoses are lower than normal weights and brains with organic focal lesions may be considerably lighter than the lowest normal brain weight. But in all estimations and comparisons of brain weights a very important factor must be taken into consideration, namely, the ratio of brain weight to skull capacity. A brain might be quite small for one subject, and yet a similar weight would be large enough for At Westborough, skull capacity is now also estimated, but the cases are as yet too few from which to draw definite conclusions as to the diminution of brain weights in persons dying insane. In most of the cases, especially senile atrophic brains, where the brain did not fall far below the average normal weight, there is sufficient disparity between the skull capacity and brain weight to suggest the importance of the relation of skull capacity to brain weights. REFERENCES. Bolton: Amentia and Dementia. Jour. of Mental Science, July, 1905. Babcock: Progressive Loss of Brain Weight. Philadelphia Med. Jour. I. No. 25. 1898. Entres: Hirngewichtsverhältnisse bei progressiver Paralyse. Inaug.-Diss. Wurzburg 1907. Handmann: Hirngewichte des Menschen. Arch. f. Anat. u. Physiol. Anat. Abt. 4. S. I. Ilberg: Gewicht von Paralytikerhirnen. Allgem. Zeitschr. f. Psych. Bd. 60 Marchand: Ueber das Hirngewicht des Menschen. 27 Bd. Abt. d. math.-phys. Mittenzweig Hirngewicht u. Geisteskrankheit. Zeitschr. f. Psych. Bd. 62. 1905. Scharpff: Hirngewicht und Psychose. Arch. f. Psych. Bd. 49. Heft I. S. 242. 1912. Southard: Am. Jour. Insan., Vol. 66, p. 673. 1910. Tigges: Gewicht des Gehirns und seiner Teile bei Geisteskrankheiten. Allg. Zeitschr. f. Psych. 1889. Bd. 45. X A REPORT ON THE THERAPEUTIC USE OF BACTERIAL VACCINES AND ON ANTI-TYPHOID VACCINATION AT WESTBOROUGH STATE HOSPITAL. BY CLARENCE C. BURLINGAME, M.D. For a short time, and that not a long while ago, bacterial vaccines held first place in the medical journals, but they have been already forgotten or abandoned by many. There are those, however, who still believe that bacterial vaccinations deserve a place among the established practices of medicine, even though they have failed as a panacea for all of the bacterial diseases. Those who have employed the vaccines most extensively have come to believe that they are reliable agents in combating certain infections, and that in them is found a valuable adjuvant in the handling of many surgical conditions. To one working among the insane, the vaccines come as a great boon, for it is not only difficult, but at times impossible to carry out usual surgical treatments successfully. A simple method of raising the body resistance against bacterial invasions and thus materially shortening the course of the infection or preventing its recurrence-such as has been demonstrated in many of the cases on which this report is basedshould, therefore, be welcomed, and more extended study given the subject to determine the conditions under which vaccine therapy may be employed to the best advantage. The period covered by this report extends from May, 1909, to April, 1912. During this time vaccine therapy has become more and more a part of the routine practice of the hospital in dealing with bacterial infections. The cases treated with vaccines include not only patients of this hospital, but also employees and a group of cases from the Lyman School for Boys, a State reform school in the town of Westborough. Most of the vaccines used were prepared at the hospital laboratory. In the beginning of the work stock vaccines were secured elsewhere. In many instances autogenous preparations were used exclusively, but more frequently Westborough Hospital stock vaccines preserved from preceding cases were employed. The results of our stock vaccines were usually good, particularly where a stapylococcus was the offending organism. While in most instances with infections of this character the stock vaccines were entirely satisfactory, cases did occur which, though responding to the stock, showed a tendency to relapse, remaining well only after administration of an autogenous vaccine. Method of Preparation.-Cultures were taken in the usual manner and the vaccine prepared from the growth resulting from the second implantation when the delay in treatment warranted, otherwise the vaccine was prepared from the first culture. The cultures were made on plain agar slants, except as stated otherwise later on in this paper. After 18 to 24 hours incubation, and the morphology of the organisms determined, 5 cc. of sterile normal saline solution were added and then by means of a finely pointed pipette the growth was washed from the slant without breaking the surface of the medium. The 5 cc. of bacterial emulsion thus obtained was transferred to a 30 cc. sterile test tube, the number per cc. of the emulsion estimated in one of two ways. The procedure with one of the methods was to mix thoroughly equal parts of the bacterial emulsion, human blood and a solution of sodium citrate and spread evenly on slides. After the slides were dried and stained, a comparative count of bacteria and erythrocytes in several fields was made. Good counting was facilitated by marking the eye piece of the microscope in quadrants. The number of red blood cells in a cmm. being an approximately known quantity, the ratio of erythrocytes and bacteria was used to compute the number of bacteria per cmm. of the emulsion. The other method made use of a Zeiss counting apparatus, proceeding as in the counting of blood cells. After determination of the density of the emulsion sufficient sterile normal saline solution was added to bring about the desired number of bacteria per cc., the whole thoroughly emulsified in the 30 cc. tube by means of a finely pointed pipette with a rubber bulb on one end. One of the workers in the laboratory rightfully considered the standardization of vaccines as only approximately correct at best, and so abandoned the more laborious methods just described and adopted a simpler method which was time saving. Experience had taught him that a certain degree of opalescence in his vaccine represented approximately 500,000 bacteria with a certain organism. Having obtained this opalescence by adding to sterile normal saline solution portions of the original bacterial emulsion, the vaccine could be further diluted to any desired strength by the addition of proper amounts of sterile salt solution. All things considered, this method of standardization does not seem entirely without merit, and it probably comes as near telling us what the strength of our vaccine is as do any of the others in common use. After all, it must be admitted that the number of bacteria in a given quantity of emulsion does not always determine the therapeutic activity of the vaccine. The individual strains of an organism may vary widely, and it is by clinical tests alone that we are able to gauge with any degree of accuracy the activity of a vaccine. Moreover, the same vaccine used for two persons often may result in reactions of very different intensity. A conservative therapeutic procedure, then, would be to make the initial dose small enough to be within the bounds of safety, and grade subsequent injections in proportion to the intensity of the reaction. Three methods of sterilization have been used in our work: heat alone, chemicals alone and heat and chemicals in combination. We have had no unfortunate clinical results with vaccines sterilized in any one of these ways. The combined method of sterilization has been equally active and produced just as good results as the other two methods of sterilization. The combined. method renders the vaccine doubly safe, and, since it does not seem to affect the activity of the vaccine, is to be recommended. Vaccines sterilized by heat alone may subsequently become inoculated, as happened several times in our work, even though the clinician using the product had used reasonable care in withdrawing from the container sufficient amounts for injection. The combined method of sterilization was produced as follows: after the desired dilution of the original emulsion had been obtained, a sufficient amount was drawn off to bring the remainder down to the 15 cc. mark on the test tube. One drop of pure lysol or carbolic acid was added and thoroughly mixed by means of a pipette. The open end of the tube was then closed with a sterile rubber cap which was punctured with a fine needle in order to permit the escape of expanded air when the tube was heated. The sealed tube was then suspended in a water bath maintained at a temperature from 58 to 60 C. for one hour. This was always. found to be sufficient to kill all bacteria. The sterility of the product was always insured by puncturing the rubber diaphragm with a sterile needle and withdrawing 1-2 cc. of the newly made. vaccine, a part of this planted on agar and the remainder in bouillon. If after 18 to 24 hours of incubation no growth occurred the product was considered safe for administration. The vaccine was either kept in the large tube or transferred to small amber colored bottles, previously sterilized with rubber caps over the mouth, the vaccine injected through the rubber caps. Slight departure from the methods of preparation just outlined was made with some of the streptococcus vaccines, especially where it seemed necessary to prepare the product speedily. The original culture was made in bouillon and incubated for twelve hours. The bouillon was then centrifugalized in sterile tubes. for five minutes at high speed. Following this the supernatant fluid was drawn off with a finely pointed pipette. The residue was emulsified with distilled water and again centrifugalized for five minutes and the supernatant fluid drawn off, leaving a residue of washed streptococci which were then emulsified with sterile normal saline solution and standardized by one of the methods already mentioned. A vaccine obtained in this manner was almost exclusively streptococcic, even when the culture was from an infection contaminated with a staphylococcus. In clinical use it proved quite as effective as streptococcus or mixed streptococcus and staphylococcus vaccines prepared by the usual methods. Staphylococcus.-The staphylococcus vaccine has so far proved to be the most reliable, and was the most extensively used. In the cases here reported, doses of from 100,000,000 to 400,000,000 were employed in general furunculosis, simple furuncles, septic infection, carbuncle, acne and abscesses. Of the cases of furunculosis, a large number came from the Lyman School for Boys, among which were not a few refractory cases which had resisted other forms of therapy for a long period. With one exception, these boys received no other treatment, nor was the diet or mode of life readjusted. This gave an exceptional opportunity for estimating the value of the treatment, since any benefit following could reasonably be considered as due to the vaccine and not merely coincident. Twenty-one of these boys treated for furunculosis showed improvement after the administration of vaccines. Forty-nine cases of furunculosis were treated, a total of 174 injections given with an average of 3.55 treatments required to effect a cure. No case failed to be relieved entirely, although in one case it was not until after the third autogenous vaccine had been made, the dose carried to 400,000,000 and repeated every third day did the very severe furunculosis yield. This case was also com plicated by pustular acne. A very severe case was No. 7768, a very poorly nourished, untidy, resistive, suicidal and violent case of dementia præcox. For six weeks he had suffered from crops of boils, and for fully five months had had single furuncles one after another. After opening these boils, efforts to keep dressings in place were flat failures, even when in mechanical restraint, because of his dexterity in freeing himself and his continual restlessness. After the third injection of a stock staphylococcus vaccine no new lesions appeared, and in three weeks there was complete recovery. Only persons who have to handle cases of this character in an excited katatonic can fully appreciate the comfort this brought to patient and physician. This man continued his untidy habits, but up to the time he was transferred to another hospital did not develop any further boils. Where time is a consideration in the preparation of an autogenous vaccine, and the staphylococcus determined it is good |