- Email: [email protected]
The Ketogenic Diet in the Treatment of Bacilluria of Females1
THE KETOGENIC DIET IN THE TREATMENT OF BACILLURIA OF FEMALES 1 EDWARD N. COOK The Mayo Clinic, Rochester, Minnesota
Chronic infection of the urinary tract of females has been and still is common and stubborn. The number of so-called urinary antiseptics has been enough to convince physicians of their lack of value. Helmholz and Clark, working independently, have suggested a new and promising treatment by means of the ketogenic diet for bacilluria of the urinary tract. Their work was prompted by the observation that the urine of epileptic patients who were on a ketogenic diet remained sterile when allowed to stand in the open for a period of days. The work of Shohl and Janney revealed that the growth of Escherichia coli was inhibited in urine at a pH of 4.6 to 5.0. Since the diet alone, in many cases, is unable to produce a pH approaching 5.0, certain acidifying drugs, such as ammonium nitrate and ammonium chloride were given in sufficient doses to enhance the acidity of the urine. As experience in the use of this form of treatment was gained, Clark and Helmholz noted that in certain cases in which the acidity of the urine reached as low a pH as 4.6 to 4.9, the simple, ferric chloride test for diacetic acid failed to reveal the presence of' ketone bodies in the urine, and the offending organism was not completely eradicated. It was then felt that some product of the ketogenic diet was as necessary to the bactericidal effect as was the low acidity. A. T. Fuller has investigated this question, and has definitely shown that this product is the levorotatory form of B-oxybutyric acid, one of the ketone bodies found in the urine of patients on the ketogenic diet. Further study by Helmholz and Osterberg has made clear also that, with an increase in the urinary acidity, a lower concentration of Boxybutyric acid is necessary to bring about the desired results. The converse of this is also true; with a lessened urinary acidity, a greater concentration of the bactericidal agent is required. They have found 1
Submitted for publication April 16, 1934. 153
THE JOURNAL OF UROLOGY, VOL. XXXII, NO. 2
154
EDWARD N. COOK
that most patients can excrete the B-oxybutyric acid in the urine, in a concentration of 0.5 per cent or more. This being so, they were able to show that with this minimal concentration, a pH of 5.5 was sufficient to bring about death of the organisms. With this brief resume of the working of this form of treatment, I shall now consider its practical application. It can be said, almost, that chronic infection of the urinary tract of females is always recurrent. In the following group of 54 cases, 4 patients gave histories of illness for only two weeks, and 1 patient had a history of recurrent attacks of burning and frequency of urination, with urgency, chills, fever and pyuria for thirty-three years. The average duration of symptoms was three and one-half years, and except for the 4 patients seen within two weeks of the beginning of their illness, and 1 patient who was seen within three weeks, the other patients all gave histories of two or more recurrent attacks. The symptoms of this condition are so well known that they bear only brief repetition. Burning and frequency of urination were present in almost all cases at some time or other. Pyuria was variable, particularly as to degree, for many of the patients were seen during a period of rem1ss10n. Cabot has mentioned that the hematuria of elderly women is caused many times by a chronic infection with colon bacilli. In 35 cases pure colon bacilluria was present, and in 8 cases this organism was found in combination with another. In this group of 43 cases gross hematuria was noted in 10 (23.3 per cent), whereas in 11 cases in which infection was caused by some other organism, hematuria was not present. Visual examination of the urine, both macroscopically and microscopically, is usually all that is necessary to arrive at a working diagnosis. A catheterized specimen of urine should be taken if the patients are females. This should be taken with a sterile catheter, after the external urethral meatus has been washed with soap and water and bathed with a mild antiseptic solution. The catheterized specimen of urine should be collected in a clean container, and while it is passing, 10 cc. of the urine should be taken for culture in a sterile tube fitted with a cotton plug. After the gross characteristics of the specimen have been noted, a sample should be centrifuged and a drop of the sediment placed on a clean glass slide and covered by an ordinary, thin coverslip. This is then examined under the high dry objective of the microscope. The various crystalline elements, erythrocytes and leukocytes, shreds of mucus, and occasionally bacteria are clearly visible if present. A count should be made of the
KETOGENIC DIET IN TREATMENT OF BACILLURIA
erythrocytes and leukocytes per high power :field. In order to rule out earthy phosphates as causes of existing cloudiness, a few cubic centimeters of acetic acid should be added to a separate sample of the urine, This will cause the cloudiness to disappear rapidly. The coverslip is then removed, and what remains of the secretion is thinly smeared over the entire slide, After drying and fixing, it should be stained by Gram's method. The stained smear is then examined under the oil immersion lens. Any existing organisms can readily be distinguished, and can be classified as to whether they are Gram-positive or Gram-negative, and TABLE 1 Results of treatment in 54 cases* OCCURRENCE ALONE
ORGANISM
Instances
Organism eradicated
Instances Per cent
OCCURRENCE WITH OTHER ORGANISM
Instances
Organism named at left eradicated
Instances Per cent
--- --- --- --- --- --Escherichia coli ..... , ..... .......... 71.4 35 25 8 7 87.5 Aerobacter aerogenes ..... ... . . ' . . . . . . 7 4 58.4 2 1 66.6 Proteus ..... , . . . . . . . . . . .. .......... l 100.0 1 2 1 66.6 Shigella .... , .. . . . . . . . . . . . . . . . . . . . . . . 0 1 1 100.0 0 0 Pseudomonas. . . . . . . . . . . . . . .......... 0 0 0 3 2 66.6 --- --- --- --- --- --Total ..... ,,., . . . . . . . . 44 31 70.4 15 11 73.3 0
••••
"
••••••
* Concerning each case (patient), the organisms which were present were recorded. In some cases more than one organism was present. For this reason the total number of "instances" is greater than the total number of cases. whether they are bacilli or cocci. Cultural methods arc necessary to identify the individual species. In the group of cases represented in table 1, the relative incidence of occurrence of the various bacilli occurring alone or in combination with other organisms may be noted. Further procedures, such as cystoscopy and pyelography were carried out when indicated, and after arriving at the complete diagnosis, the following outline of treatment was suggested for each case: A quantitative ketogenic diet was prescribed, as determined by the height and weight of the patients, who were fully instructed to adhere strictly to it. The patients were also given ammonium nitrate or ammonium chloride in doses of 6 grams daily, further to aid in acidifying the urme. They reported daily for examination, and those who had marked
156
EDWARD N. COOK
vesical irritability had the bladder lavaged with a mild solution of acetic acid. This was used to avoid offsetting the pH within the bladder.· After three days the urine was examined to determine the presence of ketone bodies; this was done by taking a few cubic centimeters and adding a similar quantity of 10 per cent ferric chloride. A deep Burgundy red color denotes the presence of diacetic acid and assures the physician that the desired end products are appearing in the urine. Osterberg recently devised a more exact test, and this is now being used to the exclusion of the one described in the foregoing. The ketone bodies should be present in three to five days, and if they are not, a check-up should be instituted. Each patient differs somewhat in his or her ability to put through these end products in the urine, and as a result a close daily scrutiny of each individual case is necessary to insure good results. Clark, in a recent publication, has gone into great detail regarding the care of these patients. In reviewing the cases of bacilluria among females seen at the clinic in the past year, the shortest time required to eradicate the infection by means of the ketogenic diet was three days. With this as a minimal time requirement for treatment, even though the average patient needed a regimen of nine and seven-tenths days, 54 patients were closely observed and were treated for at least three days. These cases form the substance of this report. The results of treatment in this group of cases are summarized briefly in table 1. There has been no selection as regards the site of the existing lesion. Cystitis and pyelonephritis were all considered together. Involvement of the upper part of the urinary tract seemed to respond equally well in the 18 cases in which only one organism was found and one or both kidneys were involved (as determined by the finding of pus and a positive culture from that side). In 14 cases the cultures were negative when the patients were dismissed. The cases in which results were not satisfactory, were studied in detail. There were 13 such cases in this group in which only one organism was found on culture, and these may be found in table 2. Case 2 is of interest because the urine from each kidney became sterile under treatment, but it was not possible to eradicate Aerobacter aerogenes from the bladder in the period allowed for treatment. The patient could not remain for further study. Cases 3, 5, 6 and 13 experienced definite relief of symptoms, but it was not possible to obtain a sufficient concentration of ketone bodies in the urine of all of them to produce a bac-
TABLE 2 Thirteen cases in which results were unsatisfactory
DURATION
DIAGNOSIS
f;)
I
ORGANISM
i:i'" "z0
"' pH ~ ---
"
m·
~
.,~ ''"" -~"r',
"' -" - ~
COMMENT
0
C'.l
0
H
-
>-1
trJ
~
years
(J
1 54
2 weeks
Cystitis
2 54
1 year
Cystitis; pyelonephritis Aerobacter aerogenes
3 27
4 59 5 63
11 years 7 months 4 years
6 55
16 years
7 53 8 63 9 64
6 years 2 years
10 30
8 years
11 57
12 27 13 58
M >-l
~
0
""< - " -<
i'-1
.MEDICATION
5 years 33 years
Ulcer of bladder Cystitis; cystocele Cystitis
Cystitis; pyelonephritis Interstitial cystitis Cystitis; pyelonephritis Cystitis; left pyonephrosis with calculus Cystitis Cystitis
Escherichia coli
Aerobacter aerogenes Escherichia coli Escherichia coli
Escherichia coli Escherichia coli Aerobacter aerogenes Escherichia coli
10
3 6.3 5 .4
9 3
NH,NO,
5.2
NH4NO,
16 2 6.7 5.4 5 3 6.4 5.3 10 2 5.5 5.0
NH.Cl NH.NO, NH,NO,
30 5 18 13
0 6.1 5.1 2 5.4 4 6. 7 5.0 4 6. 7 5.3
4
5.4 5.4
NH4Cl NH,Cl
8 3 5.9 5.2 9 2 5.9 5.5
NH1CI NH,Cl
NH,Cl NH,Cl NH4N03 NH,NO,
Patient not cooperative; did not take entire diet Negative culture from kidneys but organism still in bladder Symptoms 90 per cent improved Could not stay for further treatment Pus reduced from grade 4 to grade 1. Ketone bodies never excreted adequately, but symptoms entirely gone Never passed ketone bodies in urine Could not stay for further treatment pH could not be sufficiently depressed One negative postoperative culture
t1 >-1
t'1
>-l
.....
z
;:J t,j
::i-
~
t_zj
zH f;l tJ:j
>
() H
Escherichia coli Escherichia colia
Interstitial cystitis Escherichia coli Cystitis, pyelonephritis Escherichia coli
8 4
Could not stay for further treatment Could not stay for further treatment; symptoms 90 per cent improved Called home because of personal affairs Ketone bodies never excreted and pH not less than 5.5
r r
q !;,:j ,....
>
158
EDWARD N. COOK
tericidal effect. In cases 4, 7, 10, 11 and 12 the treatment was insufficient, as the patients were unable to stay for further treatment. Inability to lower the pH sufficiently was noted in cases 8 and 13 as a possible cause for failure. In case 9 the treatment was carried out after the operation on the kidney. One negative culture was obtained, but subsequent cultures revealed the presence of a few organisms in spite of a low pH and good ketosis. The pus content was reduced from grade 3 to only an occasional cell with complete relief of symptoms. In case 1 results were unsuccessful, as the patient would not cooperate in eating the food required. If those patients who were unable to stay for an adequate trial of treatment are disregarded, the remaining failures were due to inability to obtain satisfactory ketosis or to attain a sufficiently low pH of the unne. Helmholz has long since maintained that these two factors are necessary. Wilson, when considering failures, has called attention to the same factors and offered a helpful suggestion in an attempt to enhance the ketosis. Many of his patients had sufficient ketosis in the late afternoon and up to midnight, but from then until noon there were few if any ketone products in the urine. By giving these patients cream at regular intervals throughout the night, more uniform ketosis was obtained. He also stressed the fact that these patients should not discontinue the diet until one week following the first negative culture of urine. Helmholz has had exceptionally good results with dietary treatment of children who had chronic infection of the urinary tract associated with some urologic deformity such as hydronephrosis, hydro-ureter, or atonic bladder. However, this does not hold in our experience at the clinic with adult patients. Underwood has called attention to conditions that are liable to predispose or aggravate infection of the urinary tract ; he stated that the cases may be divided conveniently into a dynamic or neuromuscular group in which there is congenital or acquired muscular atony, and a static or mechanical group in which calculi, obstructions, diverticula, and so forth, may be responsible for continuance or aggravation of an existing infection. It has been my experience that such changes in the urinary tract, when coexistent with bacilluria, are definite hindrances to successful treatment, and the failure in case 9 was no doubt because of these changes. Further studies are now being carried out in regard to the differential renal excretion of ketone bodies in cases in which there is unilateral neuromuscular or mechanical abnormality. It is hoped
KETOGENIC DIET IN TREATMENT OF BACILLURIA
159
from this work that data may be gained that will be helpful in explaining some of the failures of treatment with the ketogenic diet. In conclusion, of the 54 cases in which various infections of the urinary tract with known microorganisms were present, satisfactory results were obtained in 31 of 44 cases in which only one organism was found, or 70.4 per cent. In the remaining 11 cases, in which more than one organism was present, :five different bacilli were found :fifteen times, and they were eradicated eleven times. From table 1 it may be noted that, contrary to earlier beliefs of Clark and Crance, each organism seems to respond equally as well to the lowered pH and bactericidal properties of the diet. REFERENCES (1) CABOT, HUGH: Personal communication to author. (2) CLARK, A. L.: Escherichia coli bacilluria under ketogenic treatment. Proc. Staff Meetings of Mayo Clinic, October 14, 1931, vi, 605-608. (3) CLARK, A. L.: The ketogenic diet in the treatment of urinary infections. Jour. Urol., February, 1934, xxxi, 193-204. (4) CRANCE, A. M.: The treatment and cure of B. coli infection of the kidney and bladder. Urol. and Cutan. Rev., August, 1928, xxxii, 495-498. (5) CRANCE, A. M.: Results in treatment of Bacillus coli infections of urinary tract, including clinical significance of ketogenic diet. Urol. and Cutan. Rev., August, 1933, xxxvii, 528-535. (6) FULLER, A. T.: The ketogenic diet; nature of bactericidal agent. Lancet, April 22, 1933, i, 855-856. (7) HELMHOLZ, H. F.: The ketogenic diet in the treatment of pyuria of children with anomalies of the urinary tract. Proc. Staff Meetings of Mayo Clinic, October 14, 1931, vi, 609-613. (8) HELMHOLZ, H.F.: The ketogenic diet in the treatment of urinary infections of childhood. Jour. Amer. Med. Assoc., October 15, 1932, xcix, 1305-1309. (9) OSTERBERG, A. E., AND HELMHOLZ, H.F.: A simple technic for clinical use in determining whether or not bactericidal action is present in ketonurine. Proc. Staff Meetings of Mayo Clinic, February 21, 1934, ix, 122. (10) SHOHL, A. T., AND JANNEY, J. H.: The growth of Bacillus coli in urine at varying hydrogen ion concentrations. Jour. Urol., April, 1917, i, 211-229. (11) UNDERWOOD, W. E.: Some aspects of the ketogenic diet in relation to urinary infection. St. Barth. Hosp. Rep., January, 1933, xi, 71-73. (12) WILSON, C. M.: Treatment of chronic B. coli infections of urinary tract by ketogenic diet. Post-Graduate Med. Jour., March, 1933, ix, 96-99.
Chronic infection of the urinary tract of females has been and still is common and stubborn. The number of so-called urinary antiseptics has been enough to convince physicians of their lack of value. Helmholz and Clark, working independently, have suggested a new and promising treatment by means of the ketogenic diet for bacilluria of the urinary tract. Their work was prompted by the observation that the urine of epileptic patients who were on a ketogenic diet remained sterile when allowed to stand in the open for a period of days. The work of Shohl and Janney revealed that the growth of Escherichia coli was inhibited in urine at a pH of 4.6 to 5.0. Since the diet alone, in many cases, is unable to produce a pH approaching 5.0, certain acidifying drugs, such as ammonium nitrate and ammonium chloride were given in sufficient doses to enhance the acidity of the urine. As experience in the use of this form of treatment was gained, Clark and Helmholz noted that in certain cases in which the acidity of the urine reached as low a pH as 4.6 to 4.9, the simple, ferric chloride test for diacetic acid failed to reveal the presence of' ketone bodies in the urine, and the offending organism was not completely eradicated. It was then felt that some product of the ketogenic diet was as necessary to the bactericidal effect as was the low acidity. A. T. Fuller has investigated this question, and has definitely shown that this product is the levorotatory form of B-oxybutyric acid, one of the ketone bodies found in the urine of patients on the ketogenic diet. Further study by Helmholz and Osterberg has made clear also that, with an increase in the urinary acidity, a lower concentration of Boxybutyric acid is necessary to bring about the desired results. The converse of this is also true; with a lessened urinary acidity, a greater concentration of the bactericidal agent is required. They have found 1
Submitted for publication April 16, 1934. 153
THE JOURNAL OF UROLOGY, VOL. XXXII, NO. 2
154
EDWARD N. COOK
that most patients can excrete the B-oxybutyric acid in the urine, in a concentration of 0.5 per cent or more. This being so, they were able to show that with this minimal concentration, a pH of 5.5 was sufficient to bring about death of the organisms. With this brief resume of the working of this form of treatment, I shall now consider its practical application. It can be said, almost, that chronic infection of the urinary tract of females is always recurrent. In the following group of 54 cases, 4 patients gave histories of illness for only two weeks, and 1 patient had a history of recurrent attacks of burning and frequency of urination, with urgency, chills, fever and pyuria for thirty-three years. The average duration of symptoms was three and one-half years, and except for the 4 patients seen within two weeks of the beginning of their illness, and 1 patient who was seen within three weeks, the other patients all gave histories of two or more recurrent attacks. The symptoms of this condition are so well known that they bear only brief repetition. Burning and frequency of urination were present in almost all cases at some time or other. Pyuria was variable, particularly as to degree, for many of the patients were seen during a period of rem1ss10n. Cabot has mentioned that the hematuria of elderly women is caused many times by a chronic infection with colon bacilli. In 35 cases pure colon bacilluria was present, and in 8 cases this organism was found in combination with another. In this group of 43 cases gross hematuria was noted in 10 (23.3 per cent), whereas in 11 cases in which infection was caused by some other organism, hematuria was not present. Visual examination of the urine, both macroscopically and microscopically, is usually all that is necessary to arrive at a working diagnosis. A catheterized specimen of urine should be taken if the patients are females. This should be taken with a sterile catheter, after the external urethral meatus has been washed with soap and water and bathed with a mild antiseptic solution. The catheterized specimen of urine should be collected in a clean container, and while it is passing, 10 cc. of the urine should be taken for culture in a sterile tube fitted with a cotton plug. After the gross characteristics of the specimen have been noted, a sample should be centrifuged and a drop of the sediment placed on a clean glass slide and covered by an ordinary, thin coverslip. This is then examined under the high dry objective of the microscope. The various crystalline elements, erythrocytes and leukocytes, shreds of mucus, and occasionally bacteria are clearly visible if present. A count should be made of the
KETOGENIC DIET IN TREATMENT OF BACILLURIA
erythrocytes and leukocytes per high power :field. In order to rule out earthy phosphates as causes of existing cloudiness, a few cubic centimeters of acetic acid should be added to a separate sample of the urine, This will cause the cloudiness to disappear rapidly. The coverslip is then removed, and what remains of the secretion is thinly smeared over the entire slide, After drying and fixing, it should be stained by Gram's method. The stained smear is then examined under the oil immersion lens. Any existing organisms can readily be distinguished, and can be classified as to whether they are Gram-positive or Gram-negative, and TABLE 1 Results of treatment in 54 cases* OCCURRENCE ALONE
ORGANISM
Instances
Organism eradicated
Instances Per cent
OCCURRENCE WITH OTHER ORGANISM
Instances
Organism named at left eradicated
Instances Per cent
--- --- --- --- --- --Escherichia coli ..... , ..... .......... 71.4 35 25 8 7 87.5 Aerobacter aerogenes ..... ... . . ' . . . . . . 7 4 58.4 2 1 66.6 Proteus ..... , . . . . . . . . . . .. .......... l 100.0 1 2 1 66.6 Shigella .... , .. . . . . . . . . . . . . . . . . . . . . . . 0 1 1 100.0 0 0 Pseudomonas. . . . . . . . . . . . . . .......... 0 0 0 3 2 66.6 --- --- --- --- --- --Total ..... ,,., . . . . . . . . 44 31 70.4 15 11 73.3 0
••••
"
••••••
* Concerning each case (patient), the organisms which were present were recorded. In some cases more than one organism was present. For this reason the total number of "instances" is greater than the total number of cases. whether they are bacilli or cocci. Cultural methods arc necessary to identify the individual species. In the group of cases represented in table 1, the relative incidence of occurrence of the various bacilli occurring alone or in combination with other organisms may be noted. Further procedures, such as cystoscopy and pyelography were carried out when indicated, and after arriving at the complete diagnosis, the following outline of treatment was suggested for each case: A quantitative ketogenic diet was prescribed, as determined by the height and weight of the patients, who were fully instructed to adhere strictly to it. The patients were also given ammonium nitrate or ammonium chloride in doses of 6 grams daily, further to aid in acidifying the urme. They reported daily for examination, and those who had marked
156
EDWARD N. COOK
vesical irritability had the bladder lavaged with a mild solution of acetic acid. This was used to avoid offsetting the pH within the bladder.· After three days the urine was examined to determine the presence of ketone bodies; this was done by taking a few cubic centimeters and adding a similar quantity of 10 per cent ferric chloride. A deep Burgundy red color denotes the presence of diacetic acid and assures the physician that the desired end products are appearing in the urine. Osterberg recently devised a more exact test, and this is now being used to the exclusion of the one described in the foregoing. The ketone bodies should be present in three to five days, and if they are not, a check-up should be instituted. Each patient differs somewhat in his or her ability to put through these end products in the urine, and as a result a close daily scrutiny of each individual case is necessary to insure good results. Clark, in a recent publication, has gone into great detail regarding the care of these patients. In reviewing the cases of bacilluria among females seen at the clinic in the past year, the shortest time required to eradicate the infection by means of the ketogenic diet was three days. With this as a minimal time requirement for treatment, even though the average patient needed a regimen of nine and seven-tenths days, 54 patients were closely observed and were treated for at least three days. These cases form the substance of this report. The results of treatment in this group of cases are summarized briefly in table 1. There has been no selection as regards the site of the existing lesion. Cystitis and pyelonephritis were all considered together. Involvement of the upper part of the urinary tract seemed to respond equally well in the 18 cases in which only one organism was found and one or both kidneys were involved (as determined by the finding of pus and a positive culture from that side). In 14 cases the cultures were negative when the patients were dismissed. The cases in which results were not satisfactory, were studied in detail. There were 13 such cases in this group in which only one organism was found on culture, and these may be found in table 2. Case 2 is of interest because the urine from each kidney became sterile under treatment, but it was not possible to eradicate Aerobacter aerogenes from the bladder in the period allowed for treatment. The patient could not remain for further study. Cases 3, 5, 6 and 13 experienced definite relief of symptoms, but it was not possible to obtain a sufficient concentration of ketone bodies in the urine of all of them to produce a bac-
TABLE 2 Thirteen cases in which results were unsatisfactory
DURATION
DIAGNOSIS
f;)
I
ORGANISM
i:i'" "z0
"' pH ~ ---
"
m·
~
.,~ ''"" -~"r',
"' -" - ~
COMMENT
0
C'.l
0
H
-
>-1
trJ
~
years
(J
1 54
2 weeks
Cystitis
2 54
1 year
Cystitis; pyelonephritis Aerobacter aerogenes
3 27
4 59 5 63
11 years 7 months 4 years
6 55
16 years
7 53 8 63 9 64
6 years 2 years
10 30
8 years
11 57
12 27 13 58
M >-l
~
0
""< - " -<
i'-1
.MEDICATION
5 years 33 years
Ulcer of bladder Cystitis; cystocele Cystitis
Cystitis; pyelonephritis Interstitial cystitis Cystitis; pyelonephritis Cystitis; left pyonephrosis with calculus Cystitis Cystitis
Escherichia coli
Aerobacter aerogenes Escherichia coli Escherichia coli
Escherichia coli Escherichia coli Aerobacter aerogenes Escherichia coli
10
3 6.3 5 .4
9 3
NH,NO,
5.2
NH4NO,
16 2 6.7 5.4 5 3 6.4 5.3 10 2 5.5 5.0
NH.Cl NH.NO, NH,NO,
30 5 18 13
0 6.1 5.1 2 5.4 4 6. 7 5.0 4 6. 7 5.3
4
5.4 5.4
NH4Cl NH,Cl
8 3 5.9 5.2 9 2 5.9 5.5
NH1CI NH,Cl
NH,Cl NH,Cl NH4N03 NH,NO,
Patient not cooperative; did not take entire diet Negative culture from kidneys but organism still in bladder Symptoms 90 per cent improved Could not stay for further treatment Pus reduced from grade 4 to grade 1. Ketone bodies never excreted adequately, but symptoms entirely gone Never passed ketone bodies in urine Could not stay for further treatment pH could not be sufficiently depressed One negative postoperative culture
t1 >-1
t'1
>-l
.....
z
;:J t,j
::i-
~
t_zj
zH f;l tJ:j
>
() H
Escherichia coli Escherichia colia
Interstitial cystitis Escherichia coli Cystitis, pyelonephritis Escherichia coli
8 4
Could not stay for further treatment Could not stay for further treatment; symptoms 90 per cent improved Called home because of personal affairs Ketone bodies never excreted and pH not less than 5.5
r r
q !;,:j ,....
>
158
EDWARD N. COOK
tericidal effect. In cases 4, 7, 10, 11 and 12 the treatment was insufficient, as the patients were unable to stay for further treatment. Inability to lower the pH sufficiently was noted in cases 8 and 13 as a possible cause for failure. In case 9 the treatment was carried out after the operation on the kidney. One negative culture was obtained, but subsequent cultures revealed the presence of a few organisms in spite of a low pH and good ketosis. The pus content was reduced from grade 3 to only an occasional cell with complete relief of symptoms. In case 1 results were unsuccessful, as the patient would not cooperate in eating the food required. If those patients who were unable to stay for an adequate trial of treatment are disregarded, the remaining failures were due to inability to obtain satisfactory ketosis or to attain a sufficiently low pH of the unne. Helmholz has long since maintained that these two factors are necessary. Wilson, when considering failures, has called attention to the same factors and offered a helpful suggestion in an attempt to enhance the ketosis. Many of his patients had sufficient ketosis in the late afternoon and up to midnight, but from then until noon there were few if any ketone products in the urine. By giving these patients cream at regular intervals throughout the night, more uniform ketosis was obtained. He also stressed the fact that these patients should not discontinue the diet until one week following the first negative culture of urine. Helmholz has had exceptionally good results with dietary treatment of children who had chronic infection of the urinary tract associated with some urologic deformity such as hydronephrosis, hydro-ureter, or atonic bladder. However, this does not hold in our experience at the clinic with adult patients. Underwood has called attention to conditions that are liable to predispose or aggravate infection of the urinary tract ; he stated that the cases may be divided conveniently into a dynamic or neuromuscular group in which there is congenital or acquired muscular atony, and a static or mechanical group in which calculi, obstructions, diverticula, and so forth, may be responsible for continuance or aggravation of an existing infection. It has been my experience that such changes in the urinary tract, when coexistent with bacilluria, are definite hindrances to successful treatment, and the failure in case 9 was no doubt because of these changes. Further studies are now being carried out in regard to the differential renal excretion of ketone bodies in cases in which there is unilateral neuromuscular or mechanical abnormality. It is hoped
KETOGENIC DIET IN TREATMENT OF BACILLURIA
159
from this work that data may be gained that will be helpful in explaining some of the failures of treatment with the ketogenic diet. In conclusion, of the 54 cases in which various infections of the urinary tract with known microorganisms were present, satisfactory results were obtained in 31 of 44 cases in which only one organism was found, or 70.4 per cent. In the remaining 11 cases, in which more than one organism was present, :five different bacilli were found :fifteen times, and they were eradicated eleven times. From table 1 it may be noted that, contrary to earlier beliefs of Clark and Crance, each organism seems to respond equally as well to the lowered pH and bactericidal properties of the diet. REFERENCES (1) CABOT, HUGH: Personal communication to author. (2) CLARK, A. L.: Escherichia coli bacilluria under ketogenic treatment. Proc. Staff Meetings of Mayo Clinic, October 14, 1931, vi, 605-608. (3) CLARK, A. L.: The ketogenic diet in the treatment of urinary infections. Jour. Urol., February, 1934, xxxi, 193-204. (4) CRANCE, A. M.: The treatment and cure of B. coli infection of the kidney and bladder. Urol. and Cutan. Rev., August, 1928, xxxii, 495-498. (5) CRANCE, A. M.: Results in treatment of Bacillus coli infections of urinary tract, including clinical significance of ketogenic diet. Urol. and Cutan. Rev., August, 1933, xxxvii, 528-535. (6) FULLER, A. T.: The ketogenic diet; nature of bactericidal agent. Lancet, April 22, 1933, i, 855-856. (7) HELMHOLZ, H. F.: The ketogenic diet in the treatment of pyuria of children with anomalies of the urinary tract. Proc. Staff Meetings of Mayo Clinic, October 14, 1931, vi, 609-613. (8) HELMHOLZ, H.F.: The ketogenic diet in the treatment of urinary infections of childhood. Jour. Amer. Med. Assoc., October 15, 1932, xcix, 1305-1309. (9) OSTERBERG, A. E., AND HELMHOLZ, H.F.: A simple technic for clinical use in determining whether or not bactericidal action is present in ketonurine. Proc. Staff Meetings of Mayo Clinic, February 21, 1934, ix, 122. (10) SHOHL, A. T., AND JANNEY, J. H.: The growth of Bacillus coli in urine at varying hydrogen ion concentrations. Jour. Urol., April, 1917, i, 211-229. (11) UNDERWOOD, W. E.: Some aspects of the ketogenic diet in relation to urinary infection. St. Barth. Hosp. Rep., January, 1933, xi, 71-73. (12) WILSON, C. M.: Treatment of chronic B. coli infections of urinary tract by ketogenic diet. Post-Graduate Med. Jour., March, 1933, ix, 96-99.