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Cystitis Emphysematosa: With a Report of the Twelfth Human Case Diagnosed at Cystoscopy
THE JOURNAL OF UROLOGY
Vol. 60, No. 5, November 1948 Printed in U.S.A.
CYSTITIS EMPHYSEMATOSA: WITH A REPORT OF THE TWELFTH HUMAN CASE DIAGNOSED AT CYSTOSCOPY MARIE ORTMAYER
Cystitis emphysematosa has been described rarely in humans. Olt, in 1921, carried its description in animals, together with emphysematosis intestinalis, back to 1915. In humans pneumatosis intestinalis has been noted at abdominal operations. Colpitis emphysematosa in women is less rare than cystitis emphysematosa. In all three of these conditions gas is found in the vesicles. It is questionable if the three represent an entity in pathology or etiology. About fifty cases of human cystitis emphysematosa are found in the literature. Of these nearly four-fifths are autopsy reports. Hueper (1926) is usually accredited with the first 11 cases. However, Eisenlohr (in 1888), Camargo (1891), Kedrowski (1898), Ruppaner (1908), Schonberg (1913: three cases), and Nowicki (1914), all antedated him. Typical gas vesicles are shown in a fairly good colored drawing in N owicki's article. Mills, in 1930, with 12 autopsied, photographed and histologically studied cases brought this entity forcefully to the attention of American physicians. Its antemortem diagnosis began in 1932 with Ravich and Katzen, who found it at cystotomy in a patient, in whom marked hematuria prevented cystoscopy. Lautenschlager's case (1911), which also came to autopsy, is sometimes given precedence as the first seen at cystoscopy, but there seems to be some doubt as to the authenticity. Since then 9 other cases discovered at cystoscopy have been reported in the following order: Antoine (1934), Redewill (2 cases 1934), Burrell (1936), Levin (1938), Lund, Zingale and O'Dowd (1939), Wilhelm (1939), Marquardt (1940), Burns (1943). Mills has added most to our understanding of the microscopic and gross pathologic picture and readers are referred to his articles, as well as to N owicki's much earlier excellent description, for details. The problem of the etiology of cystitis emphysematosa, as well as of pneumatosis intestinalis and colpitis emphysematosa has received much attention, but is not yet thoroughly settled. Eisenlohr (1888) wrote an exhaustive, if not exhausting, dissertation on the microscopic pictures of these three conditions. He regarded them as essentially similar entities and described bacteriological studies in his case of cystitis emphysematosa; certainly the first human case reported. He believed that in tissues especially vulnerable through passive congestion (as in the colpitis emphysematosa of the pregnant woman) bacteria can produce gas if tissue fluids (pH) are favorable. He noted that the bacteria from his autopsied specimen grew with gas formation on media of certain acidity, whereas on media of higher or lower acidities no gas was formed. Investigators have been varyingly successful in growing bacteria from the tissues and gas spaces and in demonstrating them in sections. Many of the autopsies have been performed so many hours after death, that bacteria found may questionably have been postmortem invaders. It would seem more conclusive to implicate bacteria found in the recovered human cases, or found antemortem in them. These 757
758
MARIE ORTMAYER
occasionally have been anaerobes such as Welchii. In general, however, they fall into the bacillus coli communis group with some minor differences of growth cultures. In 1913 S. Schonberg studied bacteria from an autopsied case which he classed in the above group and showed that some can form gas in sugar-free media and in animal tissues. Antoine (1934) has discussed this property of certain colon bacilli. Redewill has contributed some interesting ideas. He divided the etiology into four classes: 1. Anaerobe gas-formers producing generalized virulent infections, terminating fatally and associated with fulminating bladder emphysema. 2. A gas-forming colon bacillus producing cystitis and invading especially the mucosa and submucosa. 3. Abacterial cystitis emphysematosa, in diabetics with hyperglycemia of 200 mg. per cent or more, the gas supposedly being formed by enzymic action in the mucosa and submucosa of the bladder.
FIG. 1. Showing bladder with multiple negative shadows, representing collections of gas blebs seen at first cystoscopy over entire bladder wall.
4. Induced by abrasions (catheters, cystoscopes, other instrumentation), air or gas-producing bacteria being introduced thereby under the epithelium. Mills called attention to the linear, radial arrangement and localization of the gas cysts on the posterior bladder wall, in some of his cases. Cystitis emphysematosa has been produced in experimental animals. Burrell, among others, after damaging a rabbit's bladder with silver nitrate solution, injected glucose into the rabbit and reproduced cystitis emphysematosa with the colon bacillus recovered from a patient of his with a similar condition. The analysis of the gas contained in the vesicles is a further interesting problem. Carbon dioxide has been recovered from these gas cysts (Lind, Zingale and O'Dowd). It has been shown to be non-inflammable (Rosedale). Redewill designed an ingenious device for collecting the gas content from the cysts through catheters and the cystoscope. It is established, in the 11 cases diagnosed by means of cystoscopy, that a colon bacillus hemorrhagic cystitis was the usual cause for the investigation. Bloody and frequent urination were common symptoms. Quite rarely pneuma-
CYSTITIS EMPHYSEMA'l'OSA
759
turia was present, or some crepitation over the bladder was felt, or a ring of air outlining the circumference of the bladder was seen on a preliminary x-ray film. Usually the shining silvery vesicles, resembling air bubbles in their high reflectibility, were unexpectedly discovered at cystoscopy. The rapid disappearance of the gas cysts has been noted by several observers including the author (Lund, Zingale and O'Dowd; Burrell; Zanes and Doroshaw; Marquardt). Often the cases were found in untreated diabetics -with high blood sugars, but by no means always. Several patients with normal blood sugars have been reported. Attention has been called to the use of intravenous glucose transfusions in certain instances before the cystitis emphysematosa was discovered. Earlier it was thought that the condition was confined to women, but Mills and subsequently others have reported male cases. Our own patient was a diabetic -woman, 69 years old, -who had had a benign polyp of the cervix uteri removed on February 4, 1947. She had complained of
Frn. 2. Artist's drawing of author's view at first cystoscopy. Highlighting is perhaps depressed in desire to bring out purplish edges. These latter are actually seen best on closer views, whereas high reflectibility is most striking in smaller magnifications.
"gallbladder attacks" periodically for 9 years and of frequent and bloody urination for 7 days before being referred for cystoscopy on Feb. 14. Prior to that date her temperature had been 100 degrees at its highest, pulse averaged 100 and respirations 20 per minute. Fasting blood sugars, when diabetic care was instituted on Feb. 6, were 365 mg. per cent; on Feb. 7,295, on Feb. 15, 144 and Feb. 24 and thereafter, 117 mg. per cent. Urinary sugars recorded from 4 plus to traces and after Feb. 15 negative reductions were obtained. The physical examination was noncontributory except for a right tender kidney, indistinctly felt. On the day of cystoscopy the temperature was 99 F. and pulse rate 90. At cystoscopy the external genitalia and urethra appeared normal. Dirty pink urine, 270 cc, was obtained, and developed a heavy sediment on standing. The bladder presented a striking and most unusual appearance as if covered everywhere by groups of air bubbles. Many were hemorrhagic in their circumference.
760
MARIE ORTMAYER
All gave a high light reflex and appeared to contain gas within them. The collections of blebs were seen everywhere on an inflamed mucosa, which was hemorrhagic in patches. In places the collections stood out almost tumor-like, containing 4 to 6 large gas cysts of from 4 to 10 mm. diameter each. Under the observer's eye, during cystoscopic manipulation, some of the cysts burst, collapsing suddenly while bubbles rose in the fluid medium of the bladder, leaving hemorrhagic craters of approximately 3-4 mm. across. These gas cysts were more marked in the fundus but were present on all walls and on the trigone, especially at each ureteral orifice. The latter were difficult to see, swollen, inactive and slitlike. No. 6 F. catheters were passed on each side to 20 cm. without meeting obstruction. Deep pink, very cloudy urine was obtained from the right kidney and clear white to amber urine from the left. The urine recovered from the bladder on cystoscopic examination was cloudy, red, specific gravity 1.007, albumin 4 plus, sugar 0; 350 red blood cells and 160 white blood cells per cubic millimeter. Smears showed a few gram negative bacilli. Cultures yielded B. coli.
Frn. 3. Composite close-up views, seen by author and artist at second cystoscopy. Coursing of blood vessels is shown, significant of fairly deep-lying gas in submucosa.
Urine from the right kidney contained 380 red blood cells and 190 white blood cells per cubic millimeter. Smears showed many gram negative rods, and cultures yielded B. coli. Urine from the left kidney contained 2 red blood cells and 3 white blood cells per cubic millimeter. Smears showed a rare gram negative rod, and cultures yielded B. coli. Inoculation of specimens into Petragnani medium and guinea pigs was negative for acid fast bacteria. Phenolsulphonphthalein injected intravenously appeared from the right kidney in ? minutes, and from the left 1 minute, 5 seconds. The output the first 10 minutes from the right kidney was 0.2 per cent and 15 per cent from the left; the second 10 minutes, 0.1 per cent from the right kidney and 7 per cent from the left; the third 10 minutes, 0.1 per cent from the right kidney and 4 per cent from the left. Bilateral retrograde pyelograms showed nonvisualization of the right renal pelvis and calyces, and marked dilatation, redundancy and kinking of the right ureter. There was probably slight increase in the size of the left kidney, which otherwise was normal. The bladder was small and of moth eaten appearance
CYSTITIS EMPHYSEMATOSA .
761
(fig. 1). Cystoscopy was repeated Feb. 18. Cloudy, milky urine (150 cc) was obtained. The bladder picture had markedly changed. The striking grapelike clusters of gas blebs and hemorrhagic infiltration over the entire bladder mucosa seen 4 days earlier were mostly gone. A residuum of a few collections of from one to three gaseous blebs was seen chiefly in the deep fundus. A few tiny ones remained on the anterior and side walls; pricking them released gas bubbles. Numerous shallow hemorrhagic 2 mm sized depressions, or ulcerations, were situated one to two cm. apart on a very shaggy thickened mucosa. On close inspection the gas blebs showed narrow purplish rims at their peripheries with
Fm. 4. Huge hydroureter and hydronephrosis on right are seen. Bladder not shown hereon
small blood vessels coursing over some of the blebs (figs. 2 and 3). Catheterization of the right ureter yielded cloudy urine. A right retrograde pyelogram (fig. 4) showed marked hydronephrosis of the right kidney, marked dilatation of the entire right ureter, but distal few centimeters were not outlined. There was a marked change in the appearance of the bladder. It was now considered to be normal. This diabetic patient had a completely hydronephrotic right kidney and ureter removed at operation on March 6, 1947. She made an uneventful recovery and was discharged on March 22 with a fasting blood sugar of 128 mg. per cent. Her urinary sugars were controlled on a measured diet and morning dose of 25 units of P.Z.I., U. 40.
762
MARIE ORTMAYER
The pathologist's report on the specimen was: "Right inflammatory pyelonephrosis; chronic proliferative ureteritis." SUMMARY
This paper combines a short discussion of previously reported cases of human cystitis emphysematosa and records the twelfth case found at cystoscopy and reobserved subsequently in a recovered diabetic woman.
Women & Childrens Hospital, Chicago, Ill. REFERENCES ANTOINE, T.: Zentralbl. f. Gynak., 68: 2230-2235, 1934. BuRNs, R. A.: J. Ural., 49: 808-814, 1943. BURRELL, N. L.: J. Ural., 36: 690-693, 1936. DECAMARGO, A. C.: Recherches Anatomique sur L'Emphyseme Spontane des Sous-Muqueuses. These Inaugurale Univ. de Geneve. Geneve: P. Dubois, 1891, 65 pp. ErsENLOHR, W.: Beitr. z. path. Anat. u. z. allg. Path., 3: 103-156, 1888. HALL, E. R.: Canad. M.A. J., 43: 585-587, 1940. HuEPER, W.: Am. J. Path., 2: 159-166, 1926. . KEDROWSKI, W. J.: Ceptralbl. f. allg. Path. u. path. Anat., 9: 817-826, 1898. LAUTENSCHLAGER, E. L.: Inaugural Thesis. Heidelberg: Stuttgart, 1911. LEVIN, H. A.: J. Ural., 39:45, 1938. LINDENTHAL, 0.: Ztschr. f. Geburt. u. Gynak., 40: 375-389, 1899. LuND, H. G., ZINGALE, F. G. AND O'DowD, J. A.: J. Ural., 42: 684-688, 1939. MARQUARDT, C. R.: Ural. & Cutan. Rev., 44: 295-296, 1940. MILLS, R.: J. Ural., 23: 289-306, 1930. - - : J. Ural., 24: 217, 1930. : J. A. M.A., 94: 321-326, 1930. - - : Surg., Gynec. & Obst., 61: 545--551, 1930. - - : Am. J. Obst. & Gynec., 20: 688-698, 1930. NowrcKI, W.: Virchow's Arch. f. path. Anat. u. Physiol., 216: 126-141, 1914. OLT, - - : Beitr. z. path. Anat. u. allg. Path., 69: 549-557, 1921. RAVICH, A. AND KATZEN, P.: J. A. M.A., 98: 1256-1259, 1932. REDEWILL, F. H.: Ural. & Cutan. Rev., 38: 537-543, 1934. RosEDALE, R. S.: Am. J. Obst. & Gynslc., 31: 123-127, 1936. RuPPANER, E.: Frank. Ztschr. f. Path., 2: 343-355, 1908. SANES, S. AND DoROSHAW, G.D.: J. Ural., 32: 278, 1934. SCHONBERG, S.: Frank. Ztschr. f. Path., 12: 289-310, 1913. SMELISCIKOV, K.: Abstracted in Ztschr. f. ural. Chir., 29: 390, 1930. STURMER, K.: Frank. Ztschr. f. Path., 61: 376-390, 1938. WELLS, H. G.: J. Ural., 39: 391-397,.1938. WrLHELM, S. F.: N. Y. State J. Med., 39: 2054-2056, 1939.
Vol. 60, No. 5, November 1948 Printed in U.S.A.
CYSTITIS EMPHYSEMATOSA: WITH A REPORT OF THE TWELFTH HUMAN CASE DIAGNOSED AT CYSTOSCOPY MARIE ORTMAYER
Cystitis emphysematosa has been described rarely in humans. Olt, in 1921, carried its description in animals, together with emphysematosis intestinalis, back to 1915. In humans pneumatosis intestinalis has been noted at abdominal operations. Colpitis emphysematosa in women is less rare than cystitis emphysematosa. In all three of these conditions gas is found in the vesicles. It is questionable if the three represent an entity in pathology or etiology. About fifty cases of human cystitis emphysematosa are found in the literature. Of these nearly four-fifths are autopsy reports. Hueper (1926) is usually accredited with the first 11 cases. However, Eisenlohr (in 1888), Camargo (1891), Kedrowski (1898), Ruppaner (1908), Schonberg (1913: three cases), and Nowicki (1914), all antedated him. Typical gas vesicles are shown in a fairly good colored drawing in N owicki's article. Mills, in 1930, with 12 autopsied, photographed and histologically studied cases brought this entity forcefully to the attention of American physicians. Its antemortem diagnosis began in 1932 with Ravich and Katzen, who found it at cystotomy in a patient, in whom marked hematuria prevented cystoscopy. Lautenschlager's case (1911), which also came to autopsy, is sometimes given precedence as the first seen at cystoscopy, but there seems to be some doubt as to the authenticity. Since then 9 other cases discovered at cystoscopy have been reported in the following order: Antoine (1934), Redewill (2 cases 1934), Burrell (1936), Levin (1938), Lund, Zingale and O'Dowd (1939), Wilhelm (1939), Marquardt (1940), Burns (1943). Mills has added most to our understanding of the microscopic and gross pathologic picture and readers are referred to his articles, as well as to N owicki's much earlier excellent description, for details. The problem of the etiology of cystitis emphysematosa, as well as of pneumatosis intestinalis and colpitis emphysematosa has received much attention, but is not yet thoroughly settled. Eisenlohr (1888) wrote an exhaustive, if not exhausting, dissertation on the microscopic pictures of these three conditions. He regarded them as essentially similar entities and described bacteriological studies in his case of cystitis emphysematosa; certainly the first human case reported. He believed that in tissues especially vulnerable through passive congestion (as in the colpitis emphysematosa of the pregnant woman) bacteria can produce gas if tissue fluids (pH) are favorable. He noted that the bacteria from his autopsied specimen grew with gas formation on media of certain acidity, whereas on media of higher or lower acidities no gas was formed. Investigators have been varyingly successful in growing bacteria from the tissues and gas spaces and in demonstrating them in sections. Many of the autopsies have been performed so many hours after death, that bacteria found may questionably have been postmortem invaders. It would seem more conclusive to implicate bacteria found in the recovered human cases, or found antemortem in them. These 757
758
MARIE ORTMAYER
occasionally have been anaerobes such as Welchii. In general, however, they fall into the bacillus coli communis group with some minor differences of growth cultures. In 1913 S. Schonberg studied bacteria from an autopsied case which he classed in the above group and showed that some can form gas in sugar-free media and in animal tissues. Antoine (1934) has discussed this property of certain colon bacilli. Redewill has contributed some interesting ideas. He divided the etiology into four classes: 1. Anaerobe gas-formers producing generalized virulent infections, terminating fatally and associated with fulminating bladder emphysema. 2. A gas-forming colon bacillus producing cystitis and invading especially the mucosa and submucosa. 3. Abacterial cystitis emphysematosa, in diabetics with hyperglycemia of 200 mg. per cent or more, the gas supposedly being formed by enzymic action in the mucosa and submucosa of the bladder.
FIG. 1. Showing bladder with multiple negative shadows, representing collections of gas blebs seen at first cystoscopy over entire bladder wall.
4. Induced by abrasions (catheters, cystoscopes, other instrumentation), air or gas-producing bacteria being introduced thereby under the epithelium. Mills called attention to the linear, radial arrangement and localization of the gas cysts on the posterior bladder wall, in some of his cases. Cystitis emphysematosa has been produced in experimental animals. Burrell, among others, after damaging a rabbit's bladder with silver nitrate solution, injected glucose into the rabbit and reproduced cystitis emphysematosa with the colon bacillus recovered from a patient of his with a similar condition. The analysis of the gas contained in the vesicles is a further interesting problem. Carbon dioxide has been recovered from these gas cysts (Lind, Zingale and O'Dowd). It has been shown to be non-inflammable (Rosedale). Redewill designed an ingenious device for collecting the gas content from the cysts through catheters and the cystoscope. It is established, in the 11 cases diagnosed by means of cystoscopy, that a colon bacillus hemorrhagic cystitis was the usual cause for the investigation. Bloody and frequent urination were common symptoms. Quite rarely pneuma-
CYSTITIS EMPHYSEMA'l'OSA
759
turia was present, or some crepitation over the bladder was felt, or a ring of air outlining the circumference of the bladder was seen on a preliminary x-ray film. Usually the shining silvery vesicles, resembling air bubbles in their high reflectibility, were unexpectedly discovered at cystoscopy. The rapid disappearance of the gas cysts has been noted by several observers including the author (Lund, Zingale and O'Dowd; Burrell; Zanes and Doroshaw; Marquardt). Often the cases were found in untreated diabetics -with high blood sugars, but by no means always. Several patients with normal blood sugars have been reported. Attention has been called to the use of intravenous glucose transfusions in certain instances before the cystitis emphysematosa was discovered. Earlier it was thought that the condition was confined to women, but Mills and subsequently others have reported male cases. Our own patient was a diabetic -woman, 69 years old, -who had had a benign polyp of the cervix uteri removed on February 4, 1947. She had complained of
Frn. 2. Artist's drawing of author's view at first cystoscopy. Highlighting is perhaps depressed in desire to bring out purplish edges. These latter are actually seen best on closer views, whereas high reflectibility is most striking in smaller magnifications.
"gallbladder attacks" periodically for 9 years and of frequent and bloody urination for 7 days before being referred for cystoscopy on Feb. 14. Prior to that date her temperature had been 100 degrees at its highest, pulse averaged 100 and respirations 20 per minute. Fasting blood sugars, when diabetic care was instituted on Feb. 6, were 365 mg. per cent; on Feb. 7,295, on Feb. 15, 144 and Feb. 24 and thereafter, 117 mg. per cent. Urinary sugars recorded from 4 plus to traces and after Feb. 15 negative reductions were obtained. The physical examination was noncontributory except for a right tender kidney, indistinctly felt. On the day of cystoscopy the temperature was 99 F. and pulse rate 90. At cystoscopy the external genitalia and urethra appeared normal. Dirty pink urine, 270 cc, was obtained, and developed a heavy sediment on standing. The bladder presented a striking and most unusual appearance as if covered everywhere by groups of air bubbles. Many were hemorrhagic in their circumference.
760
MARIE ORTMAYER
All gave a high light reflex and appeared to contain gas within them. The collections of blebs were seen everywhere on an inflamed mucosa, which was hemorrhagic in patches. In places the collections stood out almost tumor-like, containing 4 to 6 large gas cysts of from 4 to 10 mm. diameter each. Under the observer's eye, during cystoscopic manipulation, some of the cysts burst, collapsing suddenly while bubbles rose in the fluid medium of the bladder, leaving hemorrhagic craters of approximately 3-4 mm. across. These gas cysts were more marked in the fundus but were present on all walls and on the trigone, especially at each ureteral orifice. The latter were difficult to see, swollen, inactive and slitlike. No. 6 F. catheters were passed on each side to 20 cm. without meeting obstruction. Deep pink, very cloudy urine was obtained from the right kidney and clear white to amber urine from the left. The urine recovered from the bladder on cystoscopic examination was cloudy, red, specific gravity 1.007, albumin 4 plus, sugar 0; 350 red blood cells and 160 white blood cells per cubic millimeter. Smears showed a few gram negative bacilli. Cultures yielded B. coli.
Frn. 3. Composite close-up views, seen by author and artist at second cystoscopy. Coursing of blood vessels is shown, significant of fairly deep-lying gas in submucosa.
Urine from the right kidney contained 380 red blood cells and 190 white blood cells per cubic millimeter. Smears showed many gram negative rods, and cultures yielded B. coli. Urine from the left kidney contained 2 red blood cells and 3 white blood cells per cubic millimeter. Smears showed a rare gram negative rod, and cultures yielded B. coli. Inoculation of specimens into Petragnani medium and guinea pigs was negative for acid fast bacteria. Phenolsulphonphthalein injected intravenously appeared from the right kidney in ? minutes, and from the left 1 minute, 5 seconds. The output the first 10 minutes from the right kidney was 0.2 per cent and 15 per cent from the left; the second 10 minutes, 0.1 per cent from the right kidney and 7 per cent from the left; the third 10 minutes, 0.1 per cent from the right kidney and 4 per cent from the left. Bilateral retrograde pyelograms showed nonvisualization of the right renal pelvis and calyces, and marked dilatation, redundancy and kinking of the right ureter. There was probably slight increase in the size of the left kidney, which otherwise was normal. The bladder was small and of moth eaten appearance
CYSTITIS EMPHYSEMATOSA .
761
(fig. 1). Cystoscopy was repeated Feb. 18. Cloudy, milky urine (150 cc) was obtained. The bladder picture had markedly changed. The striking grapelike clusters of gas blebs and hemorrhagic infiltration over the entire bladder mucosa seen 4 days earlier were mostly gone. A residuum of a few collections of from one to three gaseous blebs was seen chiefly in the deep fundus. A few tiny ones remained on the anterior and side walls; pricking them released gas bubbles. Numerous shallow hemorrhagic 2 mm sized depressions, or ulcerations, were situated one to two cm. apart on a very shaggy thickened mucosa. On close inspection the gas blebs showed narrow purplish rims at their peripheries with
Fm. 4. Huge hydroureter and hydronephrosis on right are seen. Bladder not shown hereon
small blood vessels coursing over some of the blebs (figs. 2 and 3). Catheterization of the right ureter yielded cloudy urine. A right retrograde pyelogram (fig. 4) showed marked hydronephrosis of the right kidney, marked dilatation of the entire right ureter, but distal few centimeters were not outlined. There was a marked change in the appearance of the bladder. It was now considered to be normal. This diabetic patient had a completely hydronephrotic right kidney and ureter removed at operation on March 6, 1947. She made an uneventful recovery and was discharged on March 22 with a fasting blood sugar of 128 mg. per cent. Her urinary sugars were controlled on a measured diet and morning dose of 25 units of P.Z.I., U. 40.
762
MARIE ORTMAYER
The pathologist's report on the specimen was: "Right inflammatory pyelonephrosis; chronic proliferative ureteritis." SUMMARY
This paper combines a short discussion of previously reported cases of human cystitis emphysematosa and records the twelfth case found at cystoscopy and reobserved subsequently in a recovered diabetic woman.
Women & Childrens Hospital, Chicago, Ill. REFERENCES ANTOINE, T.: Zentralbl. f. Gynak., 68: 2230-2235, 1934. BuRNs, R. A.: J. Ural., 49: 808-814, 1943. BURRELL, N. L.: J. Ural., 36: 690-693, 1936. DECAMARGO, A. C.: Recherches Anatomique sur L'Emphyseme Spontane des Sous-Muqueuses. These Inaugurale Univ. de Geneve. Geneve: P. Dubois, 1891, 65 pp. ErsENLOHR, W.: Beitr. z. path. Anat. u. z. allg. Path., 3: 103-156, 1888. HALL, E. R.: Canad. M.A. J., 43: 585-587, 1940. HuEPER, W.: Am. J. Path., 2: 159-166, 1926. . KEDROWSKI, W. J.: Ceptralbl. f. allg. Path. u. path. Anat., 9: 817-826, 1898. LAUTENSCHLAGER, E. L.: Inaugural Thesis. Heidelberg: Stuttgart, 1911. LEVIN, H. A.: J. Ural., 39:45, 1938. LINDENTHAL, 0.: Ztschr. f. Geburt. u. Gynak., 40: 375-389, 1899. LuND, H. G., ZINGALE, F. G. AND O'DowD, J. A.: J. Ural., 42: 684-688, 1939. MARQUARDT, C. R.: Ural. & Cutan. Rev., 44: 295-296, 1940. MILLS, R.: J. Ural., 23: 289-306, 1930. - - : J. Ural., 24: 217, 1930. : J. A. M.A., 94: 321-326, 1930. - - : Surg., Gynec. & Obst., 61: 545--551, 1930. - - : Am. J. Obst. & Gynec., 20: 688-698, 1930. NowrcKI, W.: Virchow's Arch. f. path. Anat. u. Physiol., 216: 126-141, 1914. OLT, - - : Beitr. z. path. Anat. u. allg. Path., 69: 549-557, 1921. RAVICH, A. AND KATZEN, P.: J. A. M.A., 98: 1256-1259, 1932. REDEWILL, F. H.: Ural. & Cutan. Rev., 38: 537-543, 1934. RosEDALE, R. S.: Am. J. Obst. & Gynslc., 31: 123-127, 1936. RuPPANER, E.: Frank. Ztschr. f. Path., 2: 343-355, 1908. SANES, S. AND DoROSHAW, G.D.: J. Ural., 32: 278, 1934. SCHONBERG, S.: Frank. Ztschr. f. Path., 12: 289-310, 1913. SMELISCIKOV, K.: Abstracted in Ztschr. f. ural. Chir., 29: 390, 1930. STURMER, K.: Frank. Ztschr. f. Path., 61: 376-390, 1938. WELLS, H. G.: J. Ural., 39: 391-397,.1938. WrLHELM, S. F.: N. Y. State J. Med., 39: 2054-2056, 1939.