Granuloma venereum (inguinale)

GRANULOMA

VENEREUM

(INGUINALE) *

SAMUEL A. WOLFE, M.D., F.A.C.S. AND EUGENE J. TORTORA, M.D. BROOKLYN, NEW YORK

G

RANULOMA inguinale is a chronic inflammatory disease of disputed venereal origin, clinicalIy characterized by ulcerosclerosing lesion of the skin and mucous membranes of the genitoinguina1 regions, and histologically by the presence of Donovan bodies in the monocytic cells of the exudate. In medical literature it has been variously designated as “granuloma pudenda tropicum,” “ granuloma genito-inguinale,” “ulcerating granuloma,” “granuloma venereum,” etc. The term IymphogranuIoma inguinaIe which applies to a different disease entity has led to considerable confusion. The etiology of granuloma inguinale still remains unsettled. From 1882 to 1905, the lesion was frequently considered tuberculous.8-11 Claims for spirochetal etiology were frequently made12-15 until 1905, when Donovan reported intracellular organisms supposedly protozoa. l6 Now recorded in the literature as Donovan bodies, these structures are constantly associated with the disease and, though diagnostic, have not as yet fulfilled Koch’s postulates. In this country, Symmers and Frost in 1920 were the first to recognize Donovan bodies in this lesion.r7 Other interpretations, however, have also been placed upon the nature of these incIusions. SiebertlB and Martinilg in 1907 interpreted them as diplococci. After cultural studies Aragao and ViannaZO interpreted them as schizomycetes. In 1917, WaIker21 and later Randall, Small and Belk”2 and others viewed them as Bacillus mucosus capsulatus. Castellani and MendeIsohnt3 in rg2g cuItured Gramnegative organisms possessing morphoIogic characteristics of Donovan bodies, but did

not consider them as the true cause of the disease, for inoculation produced only purulent lesions. MacIntosh25 transmitted the lesion in the human by tissue graft and from such sites Donovan bodies were found on smear and culture. He believes the Donovan body to be the cause of the disease and excIudes a fiItrabIe virus. Clinically, the disease is characterized by extreme chronicity and the absence of any tendency towards spontaneous healing. Although rectum, vagina, urethra, mouth and pharynx have been attacked, the disease shows a predilection for the external genital organs and perianal regions. In the female it often invades the vagina but only rarely has the cervix been affected. Pund and GreenbIatt”j very recentIy recorded two patients with involvement of the cervix uteri, one erroneously treated as carcinoma until pathologic study was made. Pund and Gotcher26 have reported cases involving uterus, tubes and ovaries. The period of incubation is varied. Cases with only two days’ interval from the time of sexual contact are on record, others extend to three months. There are rarely any constitutional symptoms in this interval or after the appearance of the lesion. Locally, there is Iittle pain though disturbances vary according to the organ involved, e.g., rectum, vagina, etc. Chafing, a burning sensation and itching are generaIIg described. Though most common in tropical countries, granuloma inguinale is not rare in the United States.“” It occurs as a rule during adult life, but cases are recorded in children of 2 and 6 years. 3,4 A rare case reported by Scott” was found in a 67 year oId maIe. RaciaIly negroes predominate, probably

* From the Gynecological Department, Brooklyn Cancer Institute. Read before the Brooklyn GynecoIogicaI Society, December 2, 1938.

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the resuIt of Iack of sex hygiene rather than any specia1 predisposition. SexuaI congress is beIieved to be the underIying cause.

FIG. 1. Case I. Gross appearance of the hypertrophic form of granuIoma inguinaIe. Both Iabia are the seat of firm papillary and buIbous eIevations. Superficia1 uIcers are present. Note the posterior butterfly extention onto the buttocks.

D’Aunoy and von Hamm,27 whom we freeIy quote beIow, exceIIentIy describe the gross features and divide them into three groups. Group I Iesions, caused primariIy by the infectious agent, comprise noduIar eIevations and serpiginous uIcers. The noduIes are usuaIIy onIy the beginning stage of infection and undergo further changes which Iead to deveIopment of the serpiginous uIcer, the most common and most typica manifestation of the disease. The Iesion is characterized by a soft, easiIy bIeeding granuIation tissue which breaks through the epitheIia1 Iining of the skin and mucous membrane and shows a remarkabIe tendency towards superficia1 spread aIong the moist foIds of the inguina1 and pudenda1 regions (Manson). These Iesions are onIy a few miIIimeters deep and usuaIIy show very IittIe suppuration. The exudate is serosanguineous, contains the infectious agent and spreads the disease by autoinocuIation. The rapidity with which the infection spreads varies considerabIy and heaIing may be observed in some portions of the Iesion whiIe other parts show continuous encroachment upon sound tissue.

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During the course of the disease considerabIe areas of the skin and mucous membranes are usuaIIy covered with these uIcerative Iesions, with resuItant severe anatomic mutiIation of the genitaIia and the perineum. The heaIing process is sIow and the scars produced are atrophic with partia1 depigmentation of the skin and permanent loss of hair. The second group of pathoIogic manifestations is the resuIt of a pecuIiar host reaction to the infectious agent, leading to hypertrophic and keIoid-like Iesions. The surface of the hypertrophic Iesions may be compared to the reIief map of mountainous country, with depressions between areas of piIed up tissue. In consistency the Iesions are firm and rather eIastic, the overIying skin usuaIIy showing scars of previous uIcerations. There is often very IittIe difference between this type of Iesion and the true cicatricia1 or keIoid-Iike Iesion. In the Iatter there is an apparent over-production of firm, indoIent tissue which repIaces the ulcerations. This is not a heaIed stage of the disease, but a progressive Iesion, as confirmed by the fact that the histoIogic examination shows the presence of Donovan bodies in the smaI1 nests of inffammatory ceIIs embedded in the dense coIagenous fibrous tissue obtained from such scars. The third group of pathoIogic manifestations of granuIoma inguinaIe consists of the Iesions that occur as compIications of the primary infection. The most frequent is secondary infection with aerobic or anaerobic pyogenic or saprophytic organisms. The onset of a viruIent secondary infection is usuaIIy characterized by the appearance of toxic constitutiona symptoms which are compIeteIy absent in the uncompIicated forms of granuloma venereum and by progression of the uIcerative process with the production of deep severe necrosis of soft tissues and even bone. MicroscopicaIIy, granuIoma inguinaIe reveaIs in the pure or unmixed cases a uniform histoIogic picture. The essentia1 features are: (a) hyperkeratosis which may be adjacent to areas in which the surface

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epithefium is becoming ulcerated; (b) acanthosis; (c) eIongation of the rete pegs; td) dyskeratosis of the acceIerated type

FIG. 2. Case I. HistoIogy of granuIoma inguinaIe (X 120). The surface epithelium shows hyperkeratosis. EIongation of the rete pegs with parakeratosis and suggested pear1 formation are dominant characters. The underIying connective tissue contains the inflammatory exudate.

which in some areas is such as to suggest pearl formation; (e) a nonspecific inffammatory infiItrate in the corium, in which pIasma ceIIs abound though neutrophiles and smaI1 round ceIIs may be present; (f) varying amounts of fibrous tissue deep in the Iesion; and (g) the pathognomonic ceI1 with incIusion Donovan bodies. The pathognomonic ceI1 is most distinctive. It is a reIativeIy Iarge monocyte varying from 25 to 90 microns in diameter. The many intracystoplasmic cysts are fiIled with deepIy stained bodies varying from .5 to 2 microns. These bodies as seen with hematoxyIin-eosin are round or rodlike and are grouped peripheraIIy within the cysts. They show strong affinity for this dye. In smears stained by Wright’s technique the Donovan bodies show an unstained or feebly stained body with a centraIIy pIaced baciIIus-shaped or minute coccoid chromatin body and a distinct we11 stained capsuIe. The centra1 body may aIso appear as dipIococcoid or diphtheroid in

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structure. AtypicaI forms, such as non-encapsulated bacillary or diplococcoid forms surrounded by a zone of rarefaction and

FIG. 3. Case I. The inflammatory exudate in granuloma inguinaie is predominantIy of the plasma cell type. h4onocytes, lymphocytes and occasional neutrophilcs art‘ also vncountered. (X I 20.1

zoogIear forms, are frequentIy seen. The varied interpretations of the organism’s nature may be easiIy expIained bv this The siIver stain in “tissue pIeomorphism. simpIifies identification of the organisms. The diagnosis in spite of the characteristic gross appearance is not simpIe. Chancroid, however, is easiIy differentiated. This is an acute disease, painfu1 and associated with buboes. The ulcers are phagedenic and frequently yieId to IocaI treatment. Ducrey’s baciIIus may be found on smear. TubercuIosis is excIuded only on microscopic appearance. The finding of tubercle formation and demonstration of tubercle baciIIi are concIusive. The coexistence of syphiIis and granuloma inguinale may be misIeading. The presence of treponemata in the chancre or the cIassica1 microscopic appearance of gumma easiIy estabhsh Iues. In doubtfui cases response to arsenical therapy is diagnostic. In the external genitaIia, granuIoma inguinale is frequently diagnosed as carcinoma. The two cases reported here were seen in a cancer hos-

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pitaI. VuIvar carcinoma as we11 as cancer of the skin in general, however, is rare in negroes who are so frequently subject to

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antigen obtained from suppurating Iymph nodes or from the virus-infected mouse brain (Frei test) is specific for Iympho-

FIG. 4. Case I. A group of intraceIIuIar Donovan bodies her&y impregnated with sitver. Their ova1 form and neripheral accentuation of stain are characteristic. (X 2200.)

granuIoma inguinaIe. In carcinoma there are often vestiges of IeucopIakia. Absence of Iymph node enIargement in granuIoma inguinaIe is especiaIIy striking when considering the wide extent of the IocaI Iesion. The microscopic picture is of course distinctive but hyperpIastic and acanthotic changes in granuIoma inguinaIe may sometimes Iead to confusion. LymphogranuIoma inguinaIe or Iymphopathia venereum is most frequentIy confused. CIinicaIIy, IymphogranuIoma inguinaIe is a disease of the Iymph nodes and lymphatic channels while granuIoma inguinaIe is a disease of the skin and subcutaneous tissues. The primary Iesion in IymphogranuIoma inguinaIe is rareIy encountered on the externa1 genitaIia. The vagina or cervix are the primary seat. The initia1 Iesion heals quickIy so that it is seIdom found. EnIargement and suppuration of the inguina1 Iymph nodes is frequentIy the first finding. In Iate cases a stricture of the rectum is encountered. The positive cutaneous response to injected

granuIoma inguinaIe. Even in cases where uIceration of the skin or genitaIia appears, IymphogranuIoma inguinaIe is identified by its microscopic appearance and the Frei test. Donovan bodies are Iacking. The specific response to antimoniaIs in granuIoma inguinaIe may aIso be used as further diagnostic evidence. We again emphasize the use of siIver stain for identification of Donovan bodies in biopsy specimens. Treatment in the earIy days of the disease consisted of radica1 surgica1 extirpation of the Iesion. LocaI recurrences, however, were the ruIe. CoaguIation,28 x-ray therapy,20 vaccines,30 have a11 been empIoyed. Antimony, which is a specific cure for granuIoma inguinaIe, was first empIoyed by Aragao and Vianna of BraziI. Tartar is advised, emetic given intravenousIy beginning with z C.C. of a I per cent soIution in distiIIed water, sIowIy increasing the dose unti1 IO C.C. is reached. Injections are given every second to third day and continued weekIy for two to three months after heaIing has occurred to prevent IocaI

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recurrences. It is beIieved that not more than twenty to thirty injections shouId be given in a course. Nausea, dizziness, bone

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itching and a Heeding sore in the region of the externa1 genitals. Symptoms had begun six months prior to her visit and had hecomc

FIG. 5. Case I. A monocytic ceI1, Iarge and containing a deepIy staining oval nucleus. The celI cytopIasm contains many vacuoles. At the periphery of the cel1 are classic Donovan bodies. They present a we11 stained capsule with central coccoid, diplococcoid and baciI1ar.y structures. (X r&w.)

pain or diarrhea may necessitate a temporary haIt. More recentIy a newer antimony compound has become avaiIabIe which can be used intramuscuIarIy.31 This drug, caIIed fuadin, was first introduced by KhaIiI of the University of Cairo for the treatment of biIharziasis. It was first empIoyed for granuIoma inguinaIe by T. V. WiIIiamson in this country in Ig33.32 Fourteen cases were reported in his series with exceIIent resuIts. Treatment begins with I C.C. of the drug administered intramuscuIarIy, increasing the dose unti1 5 C.C. is empIoyed. Injections are given two to three times a week unti1 heaIing occurs. In rare cases where antimony is contraindicated or produces no results, surgery, x-ray or coaguIation must be resorted to. CASE

REPORTS

CASE I. Mrs. J. J., age 55, muIatto, was first seen in the gynecoIogica1 department in October, 1935 when she compIained of vuIvar

progressiveIy worse. The itching was so severe that rubbing and scratching for relief were aImost constant. Later, white pimples appeared which broke down, bled, became red and increased in size. A discharge was aIso present and both symptoms were aggravated by waIking. She had had sexual intercourse with a West Indian six weeks before the appearance of her compIaints. There was no other exposure and the family and past persona1 history were otherwise negative. She denied Iues and gonorrhea. Examination reveaIed a granular elevated lesion which invoIved the labia majora and minora on each side, extending from the cIitoris to the fourchette. (Fig. I.) There was aIso butterfly extension toward the anus and on the posterior vagina1 wall for I inch. The surface of the Iesion presented fine granular excrescences and also round or ovoid noduIes. FocaIIy there were zones of superficia1 necrosis from which a fetid serosanguineous fluid exuded. In the posterior extension the external surface of the Iesion was smoother but its demarcation from heaIthy skin was sharply indicated by a raised indurated margin. The inguinal nodes were not enIarged.

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Several biopsies were taken which were variously reported as dyskeratosis, with marked inflammation and prickIe ceil carcinoma. The

FIG. 6. Case 11. The Iabium minus partially destroyed by a granuIomatous ulcer with a thickened serpiginous margin. Two smaIIer ulcers just anterior to the anus are aIso shown.

Frei test and Wassermann examinations were negative. The bIood count was normal. Smears studied for Donovan bodies at this time were erroneousIy reported as negative. A diagnosis of granuIoma inguinaIe was made but since severa observers believed the Iesion to be carcinoma of the vuIva, the patient was admitted for operation on December 3, 1935. The vuIva was first treated with antiseptic dressings of acriffavine for disinfection of the wound for a period of tweIve days. On January 15, 1936, vuIvectomy was performed under ether anesthesia. The postoperative course was uneventfu1 until the fourth day when beginning necrosis required remova of the sutures. Acriffavine dressings were reapplied and heaIthy granulations became apparent on the tenth day. On the twenty-first day postoperative, due to tardy healing, 5 C.C. of fuadin were given intramuscuIarly and continued twice weekly. HcaIing then progressed more satisfactoriIy and upon discharge from the hospital on March 6, epitheIization was we11advanced, but edema of the right Iabium was present. Fuadin was continued every fourth to seventh day, for a

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tota of tifteen injections. AIthough heaIing was compIete, the Iymphedema of the right Iabium persisted and was treated by x-ray therapy from June 15 to June 29, 1936. One hundred fifty radiation units were given every second day, until 750 R. units were administered. The factors were: 40 cm. S.T.D., 200 Kv., 5 M.A.; f$ mm. copper and I mm. AIuminum fiIters. On September 15, 1937, twenty-one months after operation, a recurrent uIcer 2.5 cm. in diameter appeared on the right buttock just a IittIe beIow the anus. Nine injections of fuadin were given, starting with a dose of 1.5 C.C. and increasing the quantity unti1 5 C.C. were administered. Six weeks Iater the Iesion was entireIy heaIed. The patient seen earIy in 1938 was cIinicaIIy weI1. The pathologic report of the operative specimen showed that the epitheIia1 Iayer was the seat of areas of hyperkeratosis and dyskeratosis, the Iatter resuIting in marked hypertrophy of the rete pegs with extension deep into the dermis. (Fig. 2.) There was no evidence of maIignant change of the ceIIs of the epidermis. The cutis and the subcutaneous structures were invoIved in a marked and extensive exudate. The pIasma ceI1 predominated but Iymphocytes and monocytes were encountered. (Fig. 3.) There was a superimposed acute inflammation accompanied by ulceration of the epidermis, at which sites the acute inffammatory exudate repIaced the superficia1 Iayers of the epidermis. The concIusion was that the case was one of granuIoma, with superimposed acute inflammation and uJceration. ReExaminations of the excised operative specimen and the biopsy tissues were made with the DieterIe siIver method (Fig. 4) and typica Donovan were easiIy discIosed. Smears from the recurrent Iesion in 1937, stained by the Wright method, aIso showed the organisms. (Fig. 5.) The Iesion in this case was of the noduIar type. Despite widespread invoIvement of the vuIva and inguina1 zones, the Iymph nodes were not involved. SurgicaI excision was not entirely satisfactory, but there was prompt heaIing of the operative site after the use of fuadin. A recurrence twenty-one months after operation aIso responded quickIy to the use of this agent. The diagnosis of granuIoma inguinaIe was easiIy made in the operative and earIier biopsy specimens during their restudy. The siIver stain was especiaIIy heIpfu1 in find-

Nt\r

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ing the tissl les. C ASE

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Donovan

Mrs.

Wolfe, bodies

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in excised

M. H., age 54, coIored,

was

An~crican

Jwrnal

~ISurgc~y

43’

z or 3 mm. and covered with a scant, t;erofou1 discharge. The edge of the sanguinous, and lesion was sharpIy defined, thickened

FIG. 7. Case II. The Iarge deeply stained

nucleus of a monocyte is clearIy shown. The ceI1 cytopIasm is hardIy visible. Mature Donovan bodies, irregularIN distributed, show a wet1 defined capsule with central diplococcoid, bacillary and diphtheroid formations. (X 2100.)

first seen in May 1937. She complained of itching and a sore on her vuIva and groins present since 1935. Coitus in the past six years was denied. The sore started as a pimpIe near the vuIva and graduaIIy increased in size. There was no pain. The Iesion was interpreted as luetic in origin because of a positive Wassermann and a series of saIvarsan injections was given but without resuIt. The patient was accordingIy referred by the Health Department to the BrookIyn Cancer Institute in 1936 for a biopsy. A pathologic diagnosis of pyogenic granuIoma was made and the patient returned to the Board of HeaIth for continued observation and Iuetic treatment. No improvement was exobtained. In May 1937, the gynecoIogic amination showed the foIIowing: the right Iabium minus was partIy destroyed by a granuIomatous ulcer which extended from a point just below the cIitoris downward for about 4 cm. (Fig. 6.) It was irregular in outIine and measured 4 X 3 cm. LateraIIy it reached the Iabium majus and mediaIIy encroached upon the introitus and vagina. The floor of the ulcer was somewhat granuIar, eIevated about

roIIed. It was distinctIy serpiginous. On the fourchette, just anterior to the anus, were two additiona smaI1 lesions about I .5 cm. in diameter, having similar characteristics. In the right groin, there was an oval lesion 3 x 2.5 cm. whose center was more elevated. The edge of the Iesion had the same characteristics, but was not serpiginous. Below this area, there was a heaIed depigmented scar. In the Ieft groin there was a cord-Iike thickening but distinct nodes couId not be paIpated in either groin. The vagina and cervix were normaI. Except for two externa1 hemorrhoids, recta1 examination was negative. The Wassermann and gonococcus fixation tests were negative. Injection with Frei antigen produced a positive noduIe 12 mm. in diameter. The blood count was negative except for moderate eosinophilia. Urine examination was negative. The sedimentation time was 25 minutes. Smears from the uIcer stained by Wright’s method were positive for Donovan bodies. (Fig. 7.1 The first biopsy, taken in 1936, showed tissue covered by a thickened, stratified squamous

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Iining epitheIium infiItrated by poIymorphonucIear celIs. Beneath this there was a rich Ieucocytic infiItrate containing numerous neu-

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In this case there was a coexistence positive Wassermann, positive Frei and

positive

smear

for

Donovan

of a test,

bodies.

FIG. 8. Case II. A Iarge monocyte Iies in the center of the fieId. The deeply staining nucleus is eccentricaIIy pIaced. The ceil cytoplasm presents characteristic muItipIe cysts. Donovan bodies are present though poorIy reproduced in the photograph. (X 2000.)

trophiIes and pIasma ceIIs. Areas of necrosis and pycnotic nucIear d&bris were intermingIed. CoIIections of young connective tissue ceIIs were frequent. In our restudy with hematoxylin and eosin and DieterIe techniques, Donovan bodies were found in the monocytic celIs of the exudate. (Fig. 8.) Fuadin therapy was administered by intramuscuIar injections. On May 8, 1937, 1.5 C.C. was given, foIIowed by 5 C.C. on May I I, 14 and 15. On May 18, the margins of the vuIvar uIcers were noted to have flattened out, and the edges were Iess distinct. The bases soon appeared as smooth paIe pink areas covered with a thin secretion. The groin Iesion was aIso smaIIer but did not show such prompt regression. The patient Ieft the hospita1 and was referred to a private physician for observation. In November, 1937, the Iesions were entireIy healed with the formation of depigmented scars. Repetition of the Frei test in November, 1938 showed a Iarge papule, indicating the coincidence of IymphogranuIoma inguinaIe with granuIoma inguinaIe or a repeated faIse positive reaction for IymphogranuIoma.

SaIvarsan therapy produced no effect on the cIassica1 uIcerative type of lesion. Absence of enIarged Iymph nodes and prompt response to fuadin excIuded IymphogranuIoma as the cause of the vuIvar Iesion. EarIy pathoIogic study faiIed to show the etioIogy of the Iesion, but reExamination of the tissue two years Iater by the siIver technique showed numerous Donovan bodies which were aIso present on smear examination. The rapid response to the smaI1 amount of fuadin was striking. CONCLUSIONS I.

GranuIoma inguinaIe is a chronic inflammatory Iesion of the skin and sub&taneous tissues. It occurs most frequentIy in the coIored race. The genito-inguina1 region is the site of prediIection. It appears in hypertrophic and uIcerative forms which are often mistaken for carcinoma. 2. Extensive vuIvar Iesions with absence of enIarged regiona Iymph nodes is clinicaIIy characteristic.

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3. PathoIogic reports on such Iesions are often erroneous or incompIete, yet the microscopic picture is distinctive. The tinding of Donovan bodies is conclusive. 4. A search for these bodies shouId be made in al1 genito-inguina1 Iesions presenting the clinica and pathoIogic features described. Smears and tissue sections show the organisms. 5. The Dieterle siIver stain is a great aid in the microscopic diagnosis of Donovan bodies in excised tissues. The Wright technique is simiIarIy satisfactory for examination of smears. 6. The use of antimony is specific and fuadin is the ideal drug. REFERENCES

American Journal or Sur~cry

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JEANSELME. Cours de dermatologie exotique. Paris,

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*904. WISE. Brit. M. J., I: 1274, Igo6.

13. BOSANQUET. ParasitoIogq, 2-4, 344. 14. MACLENON, A. Brit. M-J., 2: 995. 1906. 15. CLELAND. J.. and HUKKNBOTHAN. J. Troo. 12fed. (‘7 Hyg., 1’0: ;42-151, ‘gag. 16. DONOVAN, C. Indian M. Guz., 40: 411-4r4, 1905. 17. SyMMERs and FROST.J. A. ,%f. A., 74: 1304-1306, 1920.

18. SIEBERT, W. Arch. j. Scbi&y. u. Tropenhug.,

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med. Wcbnscbr., p. 2378, 1912. ARAGAO, H. DEB. New Orleans, M. @Y S. J., 70: 369-374, 19x7. Men. D. Inst. Oswaldo Crux, II: 211, ‘913. 21. WALKER, E. L. J. M. Research, 37: 427 (Jan.) 1918. 22. RANDALL, A., SMALL, J. C., and BELK, W’. I’. J. Ural., 5: 534 (June) Ig2I. ‘9.

20.

23. CASTELLANI. ALDO and MENDELSOHN. R.

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Trop. Hyg. ti Med., June 1929. 1926; 24. MCINTOSH, J. A. Tennessee M. J., Nov. J. A. M. A., 87: ggkoor, 1926. I 224-220 . , 25. PCND and GREENBLATT.Arch. Path.. 23:

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DANTEC. Prtcis 1900.

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IO. L E

26. PUND and GOTCHER.Surgery, 3: 34 (Jan.) 1938. 27. D’AUNOY, R., and VON HAAM, E. Am. J. Patb., 14: 1 (Jan.) 1938. 28. GREENWOOD,F. G. Brit. J. Radial., 4: 488 (Oct.)

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31, KAHLIL, M., NAMZI, M., PETER, F. M., SALAMI~1. DIN. M., and BELASH, M. H. Deutscbe med. Wcbnscbr., 55: I 125 (July) Ig2g. 32. WIXIAMSON, T. V., ANDERSON,J. W., KIMBKOLGII, R., and DODSON.J. A. M. A., loo: 1671, 1933. 33. RAJAM, R. V. Indian M. Gaz., 69: 372-375 iJu1~) 1934.