Eines der Haupthindernisse auf dem Wege erfolgreicher chemotherapeutischer Be-kampfung der Allgemein-infektion war stets die Toxizitat der im Reagenzglas-Versuch wirksamen Agentien bei Anwendung im lebenden Organismus. Daran scheiterte zum Beispiel die oft versuchte Einfuhrung der Edelmetalle in die praktische Therapie. Fruh ruckte das Gold meist in semen anorganischen, organischen and Kolloid-Verbindungen in den Vordergrund des Interesses. Aber leider schwanden mit der Einfuhrung vieler neuer Goldpraparate nicht die schon bei den alteren Praparaten beobachteten Nebenwirkungen. Feldt berichtete uber emn neues, von der chemischen Fabrik Schering hergestelltes, Solganal benanntes intravenos, Solganal-B benanntes intramuskular anzuwendendes Goldpraparat. Da bei Solganal and Solganal-B der therapeutische Index eenen bis dahin noch nie erreichten Wert auf weist, so wurde das Mittel mehreren Kliniken zur Pruf ung auf seinen therapeutischen Wert beim Menschen ubergeben. Ueber die Resultate der Behandlung der Lepra durch Solganal wurde schon von mehreren Autoren, Paldrock, Hoffmann, Feldt u. a. berichtet.
Es soil im folgenden uber die an der Dermatologischen Klinik der Kaiserlichen Universitat zu Fukuoka mit dem Solganal-B gesammelten Erfahrungen bei Leprosen berichtet werden. Ton 23 Lepra-Fallen, bei denen das Solganal-B injiziert wurde, mussten 3 Falle ausgeschlossen werden. Es blieben immerhin noch 20 durchbeobachtete Falle. Resultate finden sich in folgender Tabelle.
Die rnaculose Lepra zeigte eine objektive Besserung, die Resorption der Knoten war deutlich, besonders bei der lokalen Injektion. Neuralgie and Augensyrnptome wurden gebessert. Bei einem Fall von maculoser Lepra wurden Nebenwirkungen z. B. Fieber und allemeine Mattigkeit gesehen, aber bei anderen Fallen wahrend der ziemlich langen Injektionsreihen bis heute kaum. Bei der Lepra kann das Solganal-B als emn ziemlich wirksames Mittel begrusst werden.

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The following is the results of a study on lepra bacillus found in 105 leper patients examined:
1) In the tear of 105 patients acid proof bacilli are found in 11 patients (10%), the bacilli also in 13 out of 210 eyes examined. Comparing this number with that of the nasal discharges, in which the bacillil are found much frequently (66.6%) by myself, it is far less in number.
2) The bacilli in the tear are very scarce (1 or 2 in a smear).
3) The bacilli in the tear are set free, none being found in leucocytes or epitherial cells of the conjunctiva.
4) There could be stated no relationship between the existance of the bacilli in the tear and leprous changes of the eyes or other parts of the body.
5) From the experimental results above mentioned, it should be very rare incident to discharge bacilli in the tear. Moreover, the number of the bacilli in the tear is far less than that in the nasal discharg. It, therefor, can not be agreed unconditionally with the opinion, in which numerous lepra bacilli are discharged in the tear and thus eye will be one of portals for the leprous infection

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In the study on diseases of the eyes in cases of rat leprosy (1 report) the author found out that morbid changes of the eyes of 277 rats suffered from leprosy spontaneously are far milder than that of human leprosy and especially lepra bacilli in the cornea and internal tissues of the eye are very few in number. This fact stimulated the author to make an ex-primental study as to whether the bacilli of rat leprosy were difficult to invade the cornea and the internal tissues of the eye. In this experiment an injection of 0, 01cc. of an emulsion of rat leprcma (diluted in one twentyth) was made under the ocular conjunctiva of the left eye of 7 white young rats and observed these rats during 10-14 months. And then these rats which were killed or naturally died were examined to demonstrate the distribution of lepra bacilli in the whole body histologically, especially in the dominion of the eye, and the f ollwing results were obtained.
1). Bacilli of rat leprosy which were inoculated under the ocular conjunctiva produced intensive morbid changes in the eyelid and the orbit surrounding the inoculated part after 10-14 months, but encroached rarely in the internal tissues of the eye.
2). Even morbid changes were severe in late stage clinically, swelling of the eyelid, increase of exsudation, reduction of the slipt of the eye and other symptoms were merely demontrable, but without obvious turbidity of the cornea itself.
In other previous papers the occurance of leprous keratitis in rat leprosy was reported. But the author could not accept this fact, stating that it should be non-leprous changes as seen in leprous rat infected spontaneously (1 Report). By this experimental study it was believed to give an another proof.
3). The changes in the tissues round the eye-ball, the eyelid and glandullar tissues were very intensive and in severe cases the interior of granulated leproma-like part changed into gangrene.
4). Only few lepra cells were found in the cornea intruding into its parenchymal layers. Merely in two eases of intensive morbid changes a deep intrusion of the bacilli toward the center of the cornea was perceived. The bacilli were observed like as lepra cells, but none of isolated bacilli. Resemblings findings were noticed in rats infected spontaneously and not observed in the cornea of human leprosy. An infiltration was often in the upper layer of the cornea, but a healthy zone remained at the place between the former and the under part of epithelium, which corresponded to the Bowmann's membrane.
5). As for morbid changes of the sclera a part under the inoculated place was intensely invaded, and a slightly deeper invasion of the bacilli was found in some cases. But in a majority the bacilli were found in the vicinity of Schlemm's canal of deeper layer, and between it and the infiltrated part of the upper sclera only a few lepra cells were seen scatterd. Remaining part was comparatively healthy.
The bacilli were seen in the ciliary body in 5 cases, among which only one case had the bacilli in the vicinity of its Schlemm's canal and others the bacilli in the canal. The bacilli, therefore, might be considered to encroach on the ciliary body from this part continuously.
The superficial layer of the sclera which was closely surrounded by leprous infiltration was invaded by lepra bacilli in a certain degree, but the affection did not reach in the deep layer. In the posterior half behind the equator a penetration of lepra bacilli was seen along the surrounding tissuses of ciliary nerve and bond vessels and the bacilli reached the chorioid, which also seemed to be the way of penetration of lepra bacilli to the internal tissues of the eye. Two ways to the internal tissues of the eyeball in front and back were found for spreed of morbid changes of leprous rats inoculated artificially under the conjunctiva.

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The results of our statistical investigations on lepers, who visited the dermato-urologic clinic of the Osaka Imperial University in the past twenty-four years from 1909 to 1932, were as follows:
1). The total number of out patients in the past 24 years was 104350, of which 2665 (2.55%) were lepers. As regards the sex, 2039 patients were male and 626 were female.
2). Number and percentage of lepers in every one year: From 1909 to 1924, the number in every one year approximatcd 100, but in 1925 it suddenly went up to 154, showing thereafter a small variation in every years. As for percentage, in 1923 there was seen the minimal percentage (1.66%), and in 1912 the maximal propotion (4.57), others pending 2 and 4 per cent.
From the above mentioned statistic, leprous out-patients in our clinic had no remarkable tendency to decrease in number, showing only a small variation.
3). The age of patients when they first visited the clinic: Patients in 21-30 years of age were largest in number (34.71%), then those 31-40 years old (20.99%), in 11-20 years old (19.06%), and followed by 51-50 years old (11.67%).
4). The age of a provable onset of the disease: In the puverty the onset of the disease was seen most frequently, namely, 21-30 years old (34.52%), 12-20 years old (23.45%), ane 31-40 years old (18.35%).
5). Clinical types: L. maculosa 1607 (60.30%), L. nervorum 692 (25.98%), L, tuberosum 177 (6.650), L. mixta 172 (6.45%), L. mutilans (0.49%), unknown 5(0.19%).
6). Localisation of leprous changes: The frequency of appearance of changes on different parts were as follows; upper extremity (30.35%), face (25.59%), lower extremity (25.34%), dorsum, breast and belly (8.76%), neck (5.31%), nates (2.45%), head (2.23%).
7). First leprous change was said to be found in the following parts; upper extremity (33.94%), lower extremity (27.09), face (27.24%), dorsum, breast and belly (6.67%), neck (2.22%), head (2.07%), nates (1.51%).
8). Incipient symptom noticed by patient themselves or by others: Anaesthesia and Hypaesthesia were found in nearly one half or all cases as an incipient symptom. Macula also appeared in a high rate, but other symptoms in a far less percentage.
9). The number of patients who visited the clinic in the following four seasons: The disease was seen in the largest number in spring (35.93%), then in summer (25.62%), in winter (19.83%) and finally in autumn (18.62%).
10). The distribution of the cases of lepers. More than a half of the cases who visited our clinic lived in the vicinity of Osaka. This fact seemed to depend upon the convenient site of the clinic for the visit of the patients.
11). Occupation of patients: Farmers (32.69%), tradesmen (21.33%), workers (21.35%), without difinite occupations (11.81%), etc.
In the statistics one third of the lepers were found in farmers. As in Japan, however, more than one half of the population were engaged in agriculture, so the opinion that farmers might be specially exposed to the danger of leprous infection, should not be correct.
12). According to the blood relation, fathers or mothers were said to be leprous in 13 cases of the patients, grandparents and uncles or aunts in 9, and brothers or sisters in 7

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In the first report of the studies on eye-diseases of rat leprosy, the author, after a histological investigation on the dominion of the eye of leprous rats spontaneously infected described that its morbid change continuously came from the surrounding part and espe-cially was accompanied by severe cases which had lepra bacilli in the hypoderma and viscera and asserted that the source of infection was chiefly in the inside of the body. Thus the author was greatly interested in giving experimental verification of this fact by certain methods as those in the various experiments of tuberculous eye-diseases and wished to give an experimental proof about the path of infection of eye-diseases in cases of human leprosy which was a vexed question.
1) Through white rats which were treated by a subcutaneous injection of an emulsion rat leproma in the abdominal wall showed considerable morbid changes in the whole body, there were only a few animals which have morbid changes in the dominion of the eye. But some of rats, which demonstrated an elevated ulcer in the inoculated site and have an extremely enfeebled general condition showed morbid changes in the eye-dominion. These changes did not seem to be producted continuously from the surrounding tissues, but it was confirmed by many observation that they were caused by an infection meta-statically through the blood stream.
2) When the hypoderma of brow was selected as an inoculated site, the transition of morbid changes took a long time gradually and continuously toward the eyeball and finally came to encroach in the vicinity of the cornea and the Schlemm's canal. No ulcer in the inoculated part was found in this experiment and the changes of eye-dominion were transmitted chiefly continuously from the brow, but not metastatically through the blood.
3) The author examined whether or not the infection was possible from the outside of the body by means of dropping an emulsion of leproma into the conjunctival sac. In this experiment bacilli of rat leprosy were found in their submaxillary glands, penetrating the conjunctiva like tubercle bacilli in young or slighly grown-up rats, whose nasolacrymal ducts were closed. But simultaneously the bacilli were left very scarcely in the eye-dominion and developed rarely morbid changes like the tubercle bacilli. In this experiment among white matured rats those with closed nasolacrymal ducts were often invaded by the bacilli, but those with opend ducts were not so. This results indicated the difference between this and experiments with tubercle bacilli, and that the infectious power of the bacilli of rat leprosy was not so strong.
According to the experimental result bacilli of rat leprosy could enter through the conjunctiva into the body like tubercle bacilli by means of dropping an emulsion of leproma. But as little morbid changes developed directly in the site of dropping the bacilli, leprous changes of the eye should be considered to be caused by the transmission of the bacilli from other partsnamely infection from the inside, but not from the outside of the body.
4) As eye-diseases of leprous rat might be caused by the secondary infection from the outside, the author tried to test the secondary infection in different time by means of dropping an emulsion of the bacilli in conjunctival sac. But in rats which died relative early no morbid change in the eye was found. This fact seemed to show that the immunity existed in a weak grade as in case of tuberculosis. In rats which survived for a long time the inoculated part in the abdominal wall changed into an ulcer and in various places of the eye morbid changes were perceived. Most of these changes were in deep part of the eye and it seemed to suggest the infection by the blood stream. But some of them were rather superficial, and the author could not distinguish where the changes came from-inside or outside.

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A part of the work had been reported in No. 3, Vol. II of this journal. In this paper the results of the further continued experiment, in which 0, 003, 0, 001, 0, 0003 and 0, 000375 gram of the Burg (1/10, 1/30, 1/50 and 1/80 of the lethal dosis) was injected in rabbits intravenously or intraperitoneally. The general condition (appetite, body weight and urine) of the animals was carefully observed. After a certain times of injection the animals were killed and histological examinations were carried out with some of the internal organs. Injections were carried on nearly ten times once day or every two days or every week. For the purpose of comparing the toxicity of the drug with that of triphal an experiment with the latter (0, 005, 0, 001, and 0, 005) was made in the same manner.
With 0, 001 gram of both the drug and triphal showed a slight deleterious action upon the liver and kidney in the same degree. But with a smaller dosis than 0, 001 triphal seemed to have slightly strong deleterious action. Through 0, 006 of the drug (10 injections) showed no changes of the internal organs, triphal (6 injections) gave some desturbances even in a slight degree.
From these experimental results the drug could be stated to have a slightly weaker toxic action than triphal. Further, as the drug contained a larger amount of gold (53%) than triphal (44%), the curative action of the drug should be stronger than that of triphal

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