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Effects of Total Body Irradiation Followed by Bone Marrow Transplantation on the Disposition Kinetics of Mitomycin-C in the Rat
546
ONCOLOGY AND CHEMOTHERAPY
ONCOLOGY AND CHEMOTHERAPY Effects of Total Body Irradiation Followed by Bone Marrow Transplantation on the Disposition Kinetics of Mitomycin-C in the Rat
R. G.
BUICE,
B. C.
VEIT,
s. E.
MCALPIN,
B. J.
GURLEY AND
P. SIDHU, Department of Pharmaceutics, University of Ten-
nessee Center for the Health Sciences, and Division of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee Res. Comm. Chem. Path. Pharm., 44: 401-410 (June) 1984 Certain forms of childhood and adult leukemia have been treated successfully with a regimen that consists of 1) total body irradiation produced in a single exposure of 5 to 8 rad per minute culminating in doses as high as 1,000 rad, 2) bone marrow transplantation and 3) continued immunosuppressive drug therapy. This study addresses the issue of irradiation-induced pharmacokinetic alterations of the drug mitomycin C. The experimental group consisted of 5 male Wistar-Furth rats that had received 1,000 rad total body irradiation followed 2 hours later by intravenous administration of 3 X 108 bone marrow cells per kg. body weight. Then, 24 hours following bone marrow transplantation each animal received 10 mg./kg. mitomycin C by rapid intravenous injection. The control group consisted of an equal number of animals that underwent sham irradiation and the injection of an equivalent volume of a blank suspension medium. The disposition kinetics of mitomycin C was followed in each group by analyzing its concentration as determined by high performance liquid chromatography in serial blood samples. Computer-assisted data analysis revealed that the total body clearances and volumes of distribution in the test animals were significantly smaller than those of the control group. Radiation-induced inhibition of microsomal enzyme activity has been reported consistently. Since hepatic metabolism is one of the primary routes of mitomycin C elimination, the authors postulate that this mechanism may be responsible for the significantly smaller total body clearances observed in the test animals. They state that radiation-induced pharmacokinetic alterations may mandate changes in the dosage regimen of drugs used after total body irradiation and bone marrow transplantation. J. M. K. 1 figure, 2 tables, 13 references
Pure Primary Hyperaldosteronism Due to Adrenal Cortical Carcinoma D. J. GREATHOUSE, M. T. McDERMOTT, G. S. KIDD AND D. HOFELD, Endocrine/Metabolic Service, Department
F. of Medicine, Fitzsimmons Army Medical Center, Aurora, Colorado
Amer. J. Med., 76: 1132-1136 (June) 1984 The authors report a rare case of pure, primary hyperaldosteronism due to an adrenocortical carcinoma. Less than 35 cases of primary aldosteronism due to adrenocortical carcinoma have been reported in the literature, and only one of these cases had no evidence of concomitant increase in secretion of glucocorticoids, sex steroids and their metabolites. A 47-year-old white woman presented with hypertension that was refractory to various antihypertensive medications, including diuretics, prazosin and hydralazine. She also had persistent hypokalemia despite oral supplementation with sufficient
amounts of potassium chloride. The supine aldosterone levels as well as the levels after 3 hours of ambulation were elevated when the patient was on a normal diet with 80 mEq. per day of potassium chloride supplementation. The plasma aldosterone level was not suppressed after a diet containing 400 mEq. sodium and 140 mEq. potassium for 3 days, after intravenous infusion of normal saline for 2 hours and after administration of 9-a-fluorohydrocortisone every 12 hours for 3 doses. Urinary excretion of aldosterone was elevated. Plasma renin activity was below normal. Serum levels of cortisol, progesterone, 17hydroxyprogesterone, dehydroepiandrosterone sulfate, androstenedione, estradiol and testosterone were within normal limits, as were urinary excretions of 17-hydroxycorticoid and 17-ketosteroid, and vanillyl mandelic acid, metanephrine and catecholamines. A right adrenal mass was revealed by computerized tomography, 131 iodine-iodomethylnorcholesterol scan and adrenal angiography. The patient became normotensive and normokalemic after 3 weeks of spironolactone therapy. The right adrenal mass was excised and there was no evidence of local or distant metastasis. Histopathological examination revealed a well differentiated adrenocortical carcinoma with foci of hematopoietic activity and cells resembling pancreatic islets within the neoplasm. After 24 months of followup the patient was normotensive and normokalemic without any medication, and had no evidence of metastatic disease. This is the second reported case of pure, primary hyperaldosteronism due to an adrenocortical carcinoma that showed no evidence of increased secretion of glucocorticoids or sex steroids. N. S. D. 2 figures, 42 references
Multilocular Cyst of the Kidney: A Case Report
S.
EISENKRAFT, L. ENGLANDER, R. AND J. E. PONTES, Departments
M. WOLF, R. P. HUBEN of Urologic Oncology and Pathology, Roswell Park Memorial Institute, Buffalo, New York
J. Surg. OncoL, 27: 45-47 (Sept.) 1984
A 69-year-old woman with a right upper quadrant abdominal mass underwent ultrasonography and computerized tomography scanning, which revealed a complex cystic mass of the right kidney. Fine needle aspiration was positive for renal cell carcinoma and radical nephrectomy was done. The final pathological report demonstrated a multilocular cyst consistent with the 8 criteria of Powell: the mass was 1) unilateral, 2) solitary and 3) multilocular, while the locules 4) were not communicating and 5) had an epithelial lining, and 6) the cyst did not communicate with the renal pelvis, 7) the contralateral kidney was normal and 8) no fully developed nephrons were identified in the area of the lesion. Multilocular renal cysts usually are considered as a variant of neoplasm. Usual presentations include a mass, hematuria and, less commonly, hypertension. The conventional treatment is nephrectomy but some cysts can be removed by simple enucleation, thus, sparing the remainder of the kidney. J.D. S. 3 figures, 13 references
Renal Cell Carcinoma Presenting as Skeletal Muscle Mass G.
ALEXIOU, M. PAPADOPOULOU-ALEXIOU AND C. P. KARAKOUSIS, Department of Surgical Oncology, New York
ONCOLOGY AND CHEMOTHERAPY
ONCOLOGY AND CHEMOTHERAPY Effects of Total Body Irradiation Followed by Bone Marrow Transplantation on the Disposition Kinetics of Mitomycin-C in the Rat
R. G.
BUICE,
B. C.
VEIT,
s. E.
MCALPIN,
B. J.
GURLEY AND
P. SIDHU, Department of Pharmaceutics, University of Ten-
nessee Center for the Health Sciences, and Division of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee Res. Comm. Chem. Path. Pharm., 44: 401-410 (June) 1984 Certain forms of childhood and adult leukemia have been treated successfully with a regimen that consists of 1) total body irradiation produced in a single exposure of 5 to 8 rad per minute culminating in doses as high as 1,000 rad, 2) bone marrow transplantation and 3) continued immunosuppressive drug therapy. This study addresses the issue of irradiation-induced pharmacokinetic alterations of the drug mitomycin C. The experimental group consisted of 5 male Wistar-Furth rats that had received 1,000 rad total body irradiation followed 2 hours later by intravenous administration of 3 X 108 bone marrow cells per kg. body weight. Then, 24 hours following bone marrow transplantation each animal received 10 mg./kg. mitomycin C by rapid intravenous injection. The control group consisted of an equal number of animals that underwent sham irradiation and the injection of an equivalent volume of a blank suspension medium. The disposition kinetics of mitomycin C was followed in each group by analyzing its concentration as determined by high performance liquid chromatography in serial blood samples. Computer-assisted data analysis revealed that the total body clearances and volumes of distribution in the test animals were significantly smaller than those of the control group. Radiation-induced inhibition of microsomal enzyme activity has been reported consistently. Since hepatic metabolism is one of the primary routes of mitomycin C elimination, the authors postulate that this mechanism may be responsible for the significantly smaller total body clearances observed in the test animals. They state that radiation-induced pharmacokinetic alterations may mandate changes in the dosage regimen of drugs used after total body irradiation and bone marrow transplantation. J. M. K. 1 figure, 2 tables, 13 references
Pure Primary Hyperaldosteronism Due to Adrenal Cortical Carcinoma D. J. GREATHOUSE, M. T. McDERMOTT, G. S. KIDD AND D. HOFELD, Endocrine/Metabolic Service, Department
F. of Medicine, Fitzsimmons Army Medical Center, Aurora, Colorado
Amer. J. Med., 76: 1132-1136 (June) 1984 The authors report a rare case of pure, primary hyperaldosteronism due to an adrenocortical carcinoma. Less than 35 cases of primary aldosteronism due to adrenocortical carcinoma have been reported in the literature, and only one of these cases had no evidence of concomitant increase in secretion of glucocorticoids, sex steroids and their metabolites. A 47-year-old white woman presented with hypertension that was refractory to various antihypertensive medications, including diuretics, prazosin and hydralazine. She also had persistent hypokalemia despite oral supplementation with sufficient
amounts of potassium chloride. The supine aldosterone levels as well as the levels after 3 hours of ambulation were elevated when the patient was on a normal diet with 80 mEq. per day of potassium chloride supplementation. The plasma aldosterone level was not suppressed after a diet containing 400 mEq. sodium and 140 mEq. potassium for 3 days, after intravenous infusion of normal saline for 2 hours and after administration of 9-a-fluorohydrocortisone every 12 hours for 3 doses. Urinary excretion of aldosterone was elevated. Plasma renin activity was below normal. Serum levels of cortisol, progesterone, 17hydroxyprogesterone, dehydroepiandrosterone sulfate, androstenedione, estradiol and testosterone were within normal limits, as were urinary excretions of 17-hydroxycorticoid and 17-ketosteroid, and vanillyl mandelic acid, metanephrine and catecholamines. A right adrenal mass was revealed by computerized tomography, 131 iodine-iodomethylnorcholesterol scan and adrenal angiography. The patient became normotensive and normokalemic after 3 weeks of spironolactone therapy. The right adrenal mass was excised and there was no evidence of local or distant metastasis. Histopathological examination revealed a well differentiated adrenocortical carcinoma with foci of hematopoietic activity and cells resembling pancreatic islets within the neoplasm. After 24 months of followup the patient was normotensive and normokalemic without any medication, and had no evidence of metastatic disease. This is the second reported case of pure, primary hyperaldosteronism due to an adrenocortical carcinoma that showed no evidence of increased secretion of glucocorticoids or sex steroids. N. S. D. 2 figures, 42 references
Multilocular Cyst of the Kidney: A Case Report
S.
EISENKRAFT, L. ENGLANDER, R. AND J. E. PONTES, Departments
M. WOLF, R. P. HUBEN of Urologic Oncology and Pathology, Roswell Park Memorial Institute, Buffalo, New York
J. Surg. OncoL, 27: 45-47 (Sept.) 1984
A 69-year-old woman with a right upper quadrant abdominal mass underwent ultrasonography and computerized tomography scanning, which revealed a complex cystic mass of the right kidney. Fine needle aspiration was positive for renal cell carcinoma and radical nephrectomy was done. The final pathological report demonstrated a multilocular cyst consistent with the 8 criteria of Powell: the mass was 1) unilateral, 2) solitary and 3) multilocular, while the locules 4) were not communicating and 5) had an epithelial lining, and 6) the cyst did not communicate with the renal pelvis, 7) the contralateral kidney was normal and 8) no fully developed nephrons were identified in the area of the lesion. Multilocular renal cysts usually are considered as a variant of neoplasm. Usual presentations include a mass, hematuria and, less commonly, hypertension. The conventional treatment is nephrectomy but some cysts can be removed by simple enucleation, thus, sparing the remainder of the kidney. J.D. S. 3 figures, 13 references
Renal Cell Carcinoma Presenting as Skeletal Muscle Mass G.
ALEXIOU, M. PAPADOPOULOU-ALEXIOU AND C. P. KARAKOUSIS, Department of Surgical Oncology, New York