Volume 89 Number 5
existence of a diffusible eosinophilic factor released by lymphocytes which stimulates bone marrow production of eosinophils? The case presented here, although not demonstrating thymic-derived lymphoblasts, is consistent with the hypothesis that the hypereosinophilia is a respons e to a specific antigen of a neoplasm. CONCLUSION
Acute lymphoblastic leukemia must be considered among the causes of the HES. The severe clinical manifestations of this syndrome may occur early in the course of the leukemic process rendering the diagnosis of malignancy difficult. A role for the lymphocyte in the mechanism of eosinophilia is postulated. REFERENCES 1. RicklesFR, and Miller DR: Eosinophilic leukemoid reaction, J PEmA'rR80:418, 1972. 2. Hardy WR, and Anderson RE: The hypereosinophilic syndromes, Ann Intern Med 68:1120, 1968.
Countercurrent imm u noe le c trop h o resis of urine as well as of C S F and blood for diagnosis o f bacterial meningitis Ralph D. Feigin, M.D.,* Michael Wong, M.D., Penelope G. Shackelford, M.D., Barbara W. Stechenberg, M.D., Lisa M. Dunkle, M.D., and Sheldon Kaplan, M.D., St. Louis, Mo. COUNTERCURRENT IMMUN OELECTROPHORESIS has been utilized for the detection of bacterial antigens in From the Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, and the Division qf Infectious Diseases at St. Louis Children's Hospital. Supported by Grant No. 1RO1NSAI12284 from the National Institutes of Neurological Diseases and Stroke. *Reprint address: Department of Pediatrics, St, Louis Children's Hospital, 500 S. KingshighwaF, St. Louis, ?do. 63110.
Brief clinical and laboratory observations
773
3. Lukens JN: Eosinophilia in children, Pediatr Chin North Am 19:969, 1972. 4. BenevistiDS, and Ultmann JE: Eosinophiiic leukemia, Ann Intern Med 71:731, 1969. 5. Chusid MJ, Dale DC, West BC, and Wolff SM: The hypereosinophilic syndrome, Medicine 54:1, 1975. 6. SpitzerG, and @arson OM: Lymphoblastic leukemia with marked eosinophitia: A report of two cases, Blood 42:377, 1973. 7. Blatt PM, Rothstein G, Miller HL, and Cathey X~VJ:Loeftiers endomyocardial fibrosis with eosinophilia in association with acute lymphoblastic leukemia, Blood 44:489, 1974. 8. Basten A, Boyer MH, and Beeson PB: Mechanism of eosinophilia: I. Factors affecting the eosinophil response of rats to trichinella spiralis, J Exp Med 131:1271, 1970. 9. BastenA, and Beeson PB: Mechanism of eosinophilia. I1. Role of the lymphocyte, J Exp Med 131:1288, .1970. 10. Boyer MH, Basten A, and Beeson PB: Mechanism of eosinophilia. IIl. Suppression of eosinophilia by agents known to modify immune responses, Blood 36:458, 1970.
various body fluids. It has proved to be ofparticula r value in the diagnosis of bacterial meningitis,1-'~ and bacterial pneumonia.4'5 Evaluation of blood and cerebrospinal fluid by CIE can be performed without concentration o f these body fluids. Hence, detection of bacterial antigen, which may be present in. these fluids, can be accomplished within one hour. It has been emphasized previously that the diagnosis of bacterial meningitis by CIE may be enhanced by eValuation of urine concentrated by ethanol precipitation and that this may be of particular importance in pretreated patients? Generally, an ethanol precipitation technique requiring considerable technical attentmn over a period of several hours has been utilized, 1'5 Thus, detection of bacterial antigen in urine could not be broadly practiced in the usual community hospital laboratory. 9
.
.
)
.
.
,
Abbreviations used CIE: countercurrent immunoelectrophor-esis CSF: cerebrospinat fluid
We report the results of a prospective trial in which a rapid and simple technique has been utilized for concentrating urine. The results'document the efficacy of this system when compared to ethanol precipitation and support the contention that screening Of urine in addition to CSF and blood enhances the value of CIE as. a diagnostic test.
774
Brief clinical and laboratory observations
MATERIALS
AND METHODS
In our laboratory ethanol precipitation produces a 20-fold concentration of urine; these findings are in agreement with those noted previously? One-hundred thirty-five randomly obtained urine specimens containing bacterial antigen (Hemophilus influenzae, Streptococcus pneumoniae, or Neisseria meningittdis) were subjected to concentration by ethanol precipitation and teste d by CIE for the presence and concentration of bacterial antigen. Aliquots of the same urine specimens were concurrently concentrated using a disposable Ultrafilter system (Minicon-Bl5 concentrator; Amicon, Lexington, Mass.), A filter which has a molecular weight cut-off of 15,000 is already incorporated into the base unit. A minimum of 5 ml of urine is required for testing against each antibody. Thus, i(testing for three possible antigens is desired, three separate 5 ml aiiquots are concentrated; the Minicon-B15 system permits concentration of 10 aliquots concurrently. Urine can be concentrated five- to i00-fold, but for the purpose of this study, urine was Concentrated routinely to the line indicating a concentration of 50-fold. Following concentration by the Minicon-B15 system, urines were tested for the presence and concentration of bacterial antigens by CIE and the results compared to those achieved with ethanol precipitin techniques. Countercurrent immunoelectrophoresis also was performed upon CSF-, blood, and random urine specimens obiained at the time of admission from children enrolled after July, 1975, in our on-going prospective study of bacterial meningitis. ~ Countercurrent immunoelectrophoresis was performed, utilizing techniques and antisera reported previously. 1 Countercurrent immunoelectrophoresis also was performed upon urine obtained daily following admission in patients receiving intravenous antibiotic therapy. RESULTS A 20-fold concentration of urine by ethanol precipita. tion contained more antigen than that found following concentration tO the 20-fold line utilizing the MiniconB15 system. Concentration of urine to the 50-fold line by the Minicon-B15 system provided concentrations of antigen in urine which were identical to those achieved by the ethanol precipitin technique in 110 of the 138 specimens tested. Antigen was detected by ethanol precipitation but not by the Minicon-B15 system in 6% of specimens, whereas in 14%, antigen was detected by the Minicon but not by the ethanol precipitin technique. On this basis, a 50-fold concentration of urine was utilized for evaluation of clinical specimens. The results achieved by CIE are shown in Table I. Only patients who were positive on CSF culture and in whom
The ,lournal of Pediatrics November 1976
CSF, blood, and urine were evaluated concurrently have been included. It is apparent that definitive diagnosis coulcl be made by CIE of urine in 100% of patients with H. influenzae or N. meningitidis meningitis who were evaluated and in almost 80% of those with meningitis due to S. pneumoniae. In four patients with H. influenzae meningitis, CIE in blood and CSF were negative but urine CIE was positive. In five patients with meningitis due to S. pneumoniae who had been pretreated with antibiotics cultures of blood and CSF were negative but urine CIE was uniformly positive. The antibiotic therapy provided was associated with prompt clinical improvement in all of the patients. Blood obtained each day following admission generally was CIE negative by Day 3. CSF obtained on Day 12 was Uniformly culture and CiE negative. In contrast, urine remained positive for bacterial antigen for a minimum of two and for as long as 168 days (median duration of CIE positive urine was seven days). DISCUSSION Michaels and Poziviak ~'previously screened the urine of children with pneumococcal pneumonia utilizing an Amicon system in which urine was concentrated approximately 10-f01d. No comparison of this technique to the ethanol precipitin procedure was described. The present report documents the efficacy of the Amicon (MiniconB15) syitem for concentration of urine prior to CIE and suggests the degree of concentration required to achieve results which may be comparable to those obtained by precipiiation with ethanol. The Minicon-B15 is commercially available, effective, and the time required for concentration to the 50-fold line is about one hour. The value of testing urine in addition to CSF and blood by CIE iia children With bacterial meningitis documented subsequently by culture also has been demonstrated (Table I). The use of urine, CSF, and blood permitted a rapid etiologic diagnosis in all patients with either H. influenzae or meningococcal meningitis and in the majority of patients with pneumococcal meningitis, thus improving upon results reported previously. 1:' In our ongoing prospective study of bacterial meningitis in children, a diagnosis has been made by CIE in 12 patients who were pretreated with antibiotics and who were CSF and blood culture negative (total patient s enrolled to date-140). Use of urine in addition to CSF and blood as a body fluid for routine testing by CIE adds to the overall value of this tool for the rapid diagnosis of bacterial infection, w e would not anticipate, however, a continued success rate of 100% in documenting H. influenzae and meningococal meningitis by CIE. We sincerely appreciate the technical assistance of Mrs. Judy Wilson. We thank Ms. Judy Rogers for help in the preparation and Dr. Philip R. Dodge for review and Critical appraisal of the
Volume 89 Number 5
Brief clinical and laboratory observations
775
Table 1. Results o f screening of b o d y fluids by c o u n t e r c u r r e n t i m m u n o e l e c t r o p h o r e s i s *
No. of patients tested CIE positive (%) CSF Blood Urine~ Diagnosis possible by CIE at admission (CSF, blood, or urine positive)
H. influenzae type B
Streptococcus pneumoniae
Neisseria meningitidis
64
14
6
57 38 61 64
(89.1) (59.4) (96.9) (100.0)
11 6 7 11
(78.5) (42.9) (50.0) (78.5)
4 4 5 6
(66.7) (66.7) (83.3) (100.0)
*Only patients who proved subsequently to be positive by culture are included in this table. Antisera utilized for screening: H. influenzae, type b (Hyland Laboratories); N. meningitidis, A, C, andD (Burroughs-WellcomeCo.); N. meningitidis group B (National Institutes of Health equine meningococcal group B antiserum); S. pneumoniae, Omniserum, and individual pools (State Serum Institut, Copenhagen, Denmark). tUrine concentrated 50 fold by Minicon-B15 concentrator. manuscript. We thank Dr. George McCracken for his interest and for providing us with the group 13 meningococcal antiserum.
REFERENCES 1. Shackelford PG, Campbell J, and Feigin RD: Countercurrent immunoelectrophoresis in the evaluation of childhood infections, J PEDIATR 85:478, 1974. 2. Ingrain DL, O'Reilly RJ, Peter G, Anderson P, and Smith PH: Systemic capsular antigen, clinical course and antibody response in Hemophilus influenzae b meningitis, Pediatr Res 7:369, 1973.
Hyperuricemia and renal failure-presenting manifestations of occult hematologic malignancies Robert H. Yolken, M.D.,* and Denis R. Miller, M.D., N e w York, N. Y.
H Y P E R U R I C E M I A with s u b s e q u e n t renal failure is a well-known complication of the t r e a t m e n t o f l e u k e m i a a n d l y m p h o m a . 1 It is also true, however, t h a t hyperuricemia was k n o w n to occur before c h e m o t h e r a p e u t i c drugs From the Division of Pediatric Hematology-Oncology, New York Hospital-Cornell Medical Center. Supported in part by The Children's Blood Foundation and by grant CA 14557, National Cancer Institute. *Reprint address: Department of Pediatrics, Division of Pediatric Hematology-Oncology, New York Hospital, 525 East 68th St., New York, N.Y. 10021.
3. Feigin RD, Stechenberg BW, Chang M J, Dunkle LM, Wong ML, Palkes H, Dodge PR, and Davis H: Prospective evaluation of treatment of Hemophilus influenzae meningitis, J PEDIATR 88:542, 1976. 4. Michaels RH, and Poziviak CS: Countercurrent immunoelectrophoresis for the diagnosis of pneumococcal pneumonia in children, J PEDIATR 88:72, 1976. 5. Coonrod JD, and Rytel MW: Detection of type-specific pneumococcal antigens by counterimmunoelectrophoresis. I. Methodology and immunologic properties of pneumococcal antigens, J Lab Clin Med 81:770, 1973.
were available a n d t h a t h y p e r u r i c e m i a occurs in u n t r e a t e d patients with hematologic malignancies. 2 ~ We recently h a d three patients w h o presented with h y p e r u r i c e m i a a n d renal failure, initial hematologic evaluations did n o t d e m o n s t r a t e any evidence of malignancy, b u t subsequently it b e c a m e evident that a m a l i g n a n t hematologic condition was the cause of the hyperuricemia.
CASE R E P O R T S Case 1. Patient J. M. was a 12-year-old boy who presented with lethargy, vomiting, and headache. Initial physical examination revealed a listless boy with a blood pressure of 178/120 mm Hg. He had no adenopathy or organomegaly. Joints and extremities were normal. His father had had a renal stone of indeterminate etiology removed six months previousiy. The patient had worked with toluene-containing airplane glue in a small room for a twoweek period one month prior to his illness. He denied glue sniffing or other abuse 0f toxic substances. Initial laboratory data are presented in Table I. Twemy-four-hour excretion of uric acid with a low purine diet ranged from 1,220 mg/1.73 m 2 to 1,840 mg/l.73 m s (normal range: 270-460 mg)? drip-infusion pyelogram revealed faint visualization of normal-sized kidneys. The following laboratory determinations were normal or negative: anti-nuclear antibody, serum complement concentration, anti-streptococcal antibodies, measurements of liver function, clotting factors, retrograde pyelogram, and upper gastrointestinal roentgenograms. Serum concentrations of
existence of a diffusible eosinophilic factor released by lymphocytes which stimulates bone marrow production of eosinophils? The case presented here, although not demonstrating thymic-derived lymphoblasts, is consistent with the hypothesis that the hypereosinophilia is a respons e to a specific antigen of a neoplasm. CONCLUSION
Acute lymphoblastic leukemia must be considered among the causes of the HES. The severe clinical manifestations of this syndrome may occur early in the course of the leukemic process rendering the diagnosis of malignancy difficult. A role for the lymphocyte in the mechanism of eosinophilia is postulated. REFERENCES 1. RicklesFR, and Miller DR: Eosinophilic leukemoid reaction, J PEmA'rR80:418, 1972. 2. Hardy WR, and Anderson RE: The hypereosinophilic syndromes, Ann Intern Med 68:1120, 1968.
Countercurrent imm u noe le c trop h o resis of urine as well as of C S F and blood for diagnosis o f bacterial meningitis Ralph D. Feigin, M.D.,* Michael Wong, M.D., Penelope G. Shackelford, M.D., Barbara W. Stechenberg, M.D., Lisa M. Dunkle, M.D., and Sheldon Kaplan, M.D., St. Louis, Mo. COUNTERCURRENT IMMUN OELECTROPHORESIS has been utilized for the detection of bacterial antigens in From the Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, and the Division qf Infectious Diseases at St. Louis Children's Hospital. Supported by Grant No. 1RO1NSAI12284 from the National Institutes of Neurological Diseases and Stroke. *Reprint address: Department of Pediatrics, St, Louis Children's Hospital, 500 S. KingshighwaF, St. Louis, ?do. 63110.
Brief clinical and laboratory observations
773
3. Lukens JN: Eosinophilia in children, Pediatr Chin North Am 19:969, 1972. 4. BenevistiDS, and Ultmann JE: Eosinophiiic leukemia, Ann Intern Med 71:731, 1969. 5. Chusid MJ, Dale DC, West BC, and Wolff SM: The hypereosinophilic syndrome, Medicine 54:1, 1975. 6. SpitzerG, and @arson OM: Lymphoblastic leukemia with marked eosinophitia: A report of two cases, Blood 42:377, 1973. 7. Blatt PM, Rothstein G, Miller HL, and Cathey X~VJ:Loeftiers endomyocardial fibrosis with eosinophilia in association with acute lymphoblastic leukemia, Blood 44:489, 1974. 8. Basten A, Boyer MH, and Beeson PB: Mechanism of eosinophilia: I. Factors affecting the eosinophil response of rats to trichinella spiralis, J Exp Med 131:1271, 1970. 9. BastenA, and Beeson PB: Mechanism of eosinophilia. I1. Role of the lymphocyte, J Exp Med 131:1288, .1970. 10. Boyer MH, Basten A, and Beeson PB: Mechanism of eosinophilia. IIl. Suppression of eosinophilia by agents known to modify immune responses, Blood 36:458, 1970.
various body fluids. It has proved to be ofparticula r value in the diagnosis of bacterial meningitis,1-'~ and bacterial pneumonia.4'5 Evaluation of blood and cerebrospinal fluid by CIE can be performed without concentration o f these body fluids. Hence, detection of bacterial antigen, which may be present in. these fluids, can be accomplished within one hour. It has been emphasized previously that the diagnosis of bacterial meningitis by CIE may be enhanced by eValuation of urine concentrated by ethanol precipitation and that this may be of particular importance in pretreated patients? Generally, an ethanol precipitation technique requiring considerable technical attentmn over a period of several hours has been utilized, 1'5 Thus, detection of bacterial antigen in urine could not be broadly practiced in the usual community hospital laboratory. 9
.
.
)
.
.
,
Abbreviations used CIE: countercurrent immunoelectrophor-esis CSF: cerebrospinat fluid
We report the results of a prospective trial in which a rapid and simple technique has been utilized for concentrating urine. The results'document the efficacy of this system when compared to ethanol precipitation and support the contention that screening Of urine in addition to CSF and blood enhances the value of CIE as. a diagnostic test.
774
Brief clinical and laboratory observations
MATERIALS
AND METHODS
In our laboratory ethanol precipitation produces a 20-fold concentration of urine; these findings are in agreement with those noted previously? One-hundred thirty-five randomly obtained urine specimens containing bacterial antigen (Hemophilus influenzae, Streptococcus pneumoniae, or Neisseria meningittdis) were subjected to concentration by ethanol precipitation and teste d by CIE for the presence and concentration of bacterial antigen. Aliquots of the same urine specimens were concurrently concentrated using a disposable Ultrafilter system (Minicon-Bl5 concentrator; Amicon, Lexington, Mass.), A filter which has a molecular weight cut-off of 15,000 is already incorporated into the base unit. A minimum of 5 ml of urine is required for testing against each antibody. Thus, i(testing for three possible antigens is desired, three separate 5 ml aiiquots are concentrated; the Minicon-B15 system permits concentration of 10 aliquots concurrently. Urine can be concentrated five- to i00-fold, but for the purpose of this study, urine was Concentrated routinely to the line indicating a concentration of 50-fold. Following concentration by the Minicon-B15 system, urines were tested for the presence and concentration of bacterial antigens by CIE and the results compared to those achieved with ethanol precipitin techniques. Countercurrent immunoelectrophoresis also was performed upon CSF-, blood, and random urine specimens obiained at the time of admission from children enrolled after July, 1975, in our on-going prospective study of bacterial meningitis. ~ Countercurrent immunoelectrophoresis was performed, utilizing techniques and antisera reported previously. 1 Countercurrent immunoelectrophoresis also was performed upon urine obtained daily following admission in patients receiving intravenous antibiotic therapy. RESULTS A 20-fold concentration of urine by ethanol precipita. tion contained more antigen than that found following concentration tO the 20-fold line utilizing the MiniconB15 system. Concentration of urine to the 50-fold line by the Minicon-B15 system provided concentrations of antigen in urine which were identical to those achieved by the ethanol precipitin technique in 110 of the 138 specimens tested. Antigen was detected by ethanol precipitation but not by the Minicon-B15 system in 6% of specimens, whereas in 14%, antigen was detected by the Minicon but not by the ethanol precipitin technique. On this basis, a 50-fold concentration of urine was utilized for evaluation of clinical specimens. The results achieved by CIE are shown in Table I. Only patients who were positive on CSF culture and in whom
The ,lournal of Pediatrics November 1976
CSF, blood, and urine were evaluated concurrently have been included. It is apparent that definitive diagnosis coulcl be made by CIE of urine in 100% of patients with H. influenzae or N. meningitidis meningitis who were evaluated and in almost 80% of those with meningitis due to S. pneumoniae. In four patients with H. influenzae meningitis, CIE in blood and CSF were negative but urine CIE was positive. In five patients with meningitis due to S. pneumoniae who had been pretreated with antibiotics cultures of blood and CSF were negative but urine CIE was uniformly positive. The antibiotic therapy provided was associated with prompt clinical improvement in all of the patients. Blood obtained each day following admission generally was CIE negative by Day 3. CSF obtained on Day 12 was Uniformly culture and CiE negative. In contrast, urine remained positive for bacterial antigen for a minimum of two and for as long as 168 days (median duration of CIE positive urine was seven days). DISCUSSION Michaels and Poziviak ~'previously screened the urine of children with pneumococcal pneumonia utilizing an Amicon system in which urine was concentrated approximately 10-f01d. No comparison of this technique to the ethanol precipitin procedure was described. The present report documents the efficacy of the Amicon (MiniconB15) syitem for concentration of urine prior to CIE and suggests the degree of concentration required to achieve results which may be comparable to those obtained by precipiiation with ethanol. The Minicon-B15 is commercially available, effective, and the time required for concentration to the 50-fold line is about one hour. The value of testing urine in addition to CSF and blood by CIE iia children With bacterial meningitis documented subsequently by culture also has been demonstrated (Table I). The use of urine, CSF, and blood permitted a rapid etiologic diagnosis in all patients with either H. influenzae or meningococcal meningitis and in the majority of patients with pneumococcal meningitis, thus improving upon results reported previously. 1:' In our ongoing prospective study of bacterial meningitis in children, a diagnosis has been made by CIE in 12 patients who were pretreated with antibiotics and who were CSF and blood culture negative (total patient s enrolled to date-140). Use of urine in addition to CSF and blood as a body fluid for routine testing by CIE adds to the overall value of this tool for the rapid diagnosis of bacterial infection, w e would not anticipate, however, a continued success rate of 100% in documenting H. influenzae and meningococal meningitis by CIE. We sincerely appreciate the technical assistance of Mrs. Judy Wilson. We thank Ms. Judy Rogers for help in the preparation and Dr. Philip R. Dodge for review and Critical appraisal of the
Volume 89 Number 5
Brief clinical and laboratory observations
775
Table 1. Results o f screening of b o d y fluids by c o u n t e r c u r r e n t i m m u n o e l e c t r o p h o r e s i s *
No. of patients tested CIE positive (%) CSF Blood Urine~ Diagnosis possible by CIE at admission (CSF, blood, or urine positive)
H. influenzae type B
Streptococcus pneumoniae
Neisseria meningitidis
64
14
6
57 38 61 64
(89.1) (59.4) (96.9) (100.0)
11 6 7 11
(78.5) (42.9) (50.0) (78.5)
4 4 5 6
(66.7) (66.7) (83.3) (100.0)
*Only patients who proved subsequently to be positive by culture are included in this table. Antisera utilized for screening: H. influenzae, type b (Hyland Laboratories); N. meningitidis, A, C, andD (Burroughs-WellcomeCo.); N. meningitidis group B (National Institutes of Health equine meningococcal group B antiserum); S. pneumoniae, Omniserum, and individual pools (State Serum Institut, Copenhagen, Denmark). tUrine concentrated 50 fold by Minicon-B15 concentrator. manuscript. We thank Dr. George McCracken for his interest and for providing us with the group 13 meningococcal antiserum.
REFERENCES 1. Shackelford PG, Campbell J, and Feigin RD: Countercurrent immunoelectrophoresis in the evaluation of childhood infections, J PEDIATR 85:478, 1974. 2. Ingrain DL, O'Reilly RJ, Peter G, Anderson P, and Smith PH: Systemic capsular antigen, clinical course and antibody response in Hemophilus influenzae b meningitis, Pediatr Res 7:369, 1973.
Hyperuricemia and renal failure-presenting manifestations of occult hematologic malignancies Robert H. Yolken, M.D.,* and Denis R. Miller, M.D., N e w York, N. Y.
H Y P E R U R I C E M I A with s u b s e q u e n t renal failure is a well-known complication of the t r e a t m e n t o f l e u k e m i a a n d l y m p h o m a . 1 It is also true, however, t h a t hyperuricemia was k n o w n to occur before c h e m o t h e r a p e u t i c drugs From the Division of Pediatric Hematology-Oncology, New York Hospital-Cornell Medical Center. Supported in part by The Children's Blood Foundation and by grant CA 14557, National Cancer Institute. *Reprint address: Department of Pediatrics, Division of Pediatric Hematology-Oncology, New York Hospital, 525 East 68th St., New York, N.Y. 10021.
3. Feigin RD, Stechenberg BW, Chang M J, Dunkle LM, Wong ML, Palkes H, Dodge PR, and Davis H: Prospective evaluation of treatment of Hemophilus influenzae meningitis, J PEDIATR 88:542, 1976. 4. Michaels RH, and Poziviak CS: Countercurrent immunoelectrophoresis for the diagnosis of pneumococcal pneumonia in children, J PEDIATR 88:72, 1976. 5. Coonrod JD, and Rytel MW: Detection of type-specific pneumococcal antigens by counterimmunoelectrophoresis. I. Methodology and immunologic properties of pneumococcal antigens, J Lab Clin Med 81:770, 1973.
were available a n d t h a t h y p e r u r i c e m i a occurs in u n t r e a t e d patients with hematologic malignancies. 2 ~ We recently h a d three patients w h o presented with h y p e r u r i c e m i a a n d renal failure, initial hematologic evaluations did n o t d e m o n s t r a t e any evidence of malignancy, b u t subsequently it b e c a m e evident that a m a l i g n a n t hematologic condition was the cause of the hyperuricemia.
CASE R E P O R T S Case 1. Patient J. M. was a 12-year-old boy who presented with lethargy, vomiting, and headache. Initial physical examination revealed a listless boy with a blood pressure of 178/120 mm Hg. He had no adenopathy or organomegaly. Joints and extremities were normal. His father had had a renal stone of indeterminate etiology removed six months previousiy. The patient had worked with toluene-containing airplane glue in a small room for a twoweek period one month prior to his illness. He denied glue sniffing or other abuse 0f toxic substances. Initial laboratory data are presented in Table I. Twemy-four-hour excretion of uric acid with a low purine diet ranged from 1,220 mg/1.73 m 2 to 1,840 mg/l.73 m s (normal range: 270-460 mg)? drip-infusion pyelogram revealed faint visualization of normal-sized kidneys. The following laboratory determinations were normal or negative: anti-nuclear antibody, serum complement concentration, anti-streptococcal antibodies, measurements of liver function, clotting factors, retrograde pyelogram, and upper gastrointestinal roentgenograms. Serum concentrations of
