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Drug Treatment of Primary Hyperparathyroidism: Use of Clodronate Disodium
840
MISCELLANEOUS
The concentrations of metals in the diets are far higher than those of the control meal. Gross organ changes at necropsy on day 81 were not unusual among the present series, at least as compared to the control group. P.R.R. 1 table, 11 references
High-Performance Size-Exclusion Chromatography of 63 Ni-Co:nstituen.ts in Renal Cytosol and Mic.rosomes From 63 NiCb-Treated Rats F.
w.
SUNDERMAN, JR., B. L. K. MANGOLD, S. H. Y. WONG, K. SHEN, M. C. REID AND I. JANSSON, Departments of Laboratory Medicine and Pharmacology, University of Connecticut School of Medicine, Farmington, Connecticut S.
Res. Comm. Chem. Path. Pharm., 39: 477-492 (Mar.) 1983 Workers in nickel refineries have increased risks of cancers of the nose, lung, larynx and, possibly, kidney. They also may suffer nonmalignant respiratory, cutaneous and renal disturbances. Efforts are essential to elucidate the cellular uptake, transport and elimination of nickel (Ni) (11), and the mechanisms of toxicity and carcinogenicity of nickel compounds. This investigation provides the first demonstration of 63 Nicomponents in renal microsomes of 63 Ni-treated rats. Highperformance size-exclusion chromatography on silicone gel bonded macromolecules showed that solubilized, washed microsomes contain 63 Ni in 5 fractions with the same elution profiles as fractions A, B, D, E and F of renal cytosol. In addition, the solubilized microsomes contain a 63 Ni component with high molecular weight (fraction M, >700,000 daltons), which may represent 63 Ni binding to incompletely dissociated aggregates of microsomal proteins and ribonucleic acid. This study provides a rapid, convenient and reproducible technique to fractionate 63 Ni components in tissue extracts, and it demonstrates in vivo binding of 63 Ni to several constituents of renal cytosol and microsomes from 63 Ni Cb-treated rats. P.R.R. 4 figures, 2 tables, 32 references
Drug Treatment of Primary Hypelt'parathy:roidi§m: Use of Clodronate Di§odium
D. L. E.
DOUGLAS, J. A. KANIS, A. D. PATERSON, D. J. BEARD, C. CAMERON, M. E. WATSON, S. WOODHEAD, J. WILLIAMS AND R. G. G. RUSSEL, Department of Human
Metabolism and Clinical Biochemistry, University of Sheffield Medical School, Sheffield, England; Department of Urology, Royal Hallamshire Hospital, Sheffield, England; and Department of Medical Biochemistry, Welsh National School of Medicine, Cardiff, Wales Brit. Med. J., 285: 587-590 (Feb. 19) 1983 The authors studied the effects of clodronate disodium, a specific inhibitor of bone resorption, in 9 patients with primary hyperparathyroidism. Patient age ranged from 61 to 72 years. All patients had normal renal function and had biochemical evidence of hyperparathyroidism. Clodronate was given as a daily single 1 to 3.2 gm. dose before breakfast. In 2 of 3 patients with skeletal pain the pain decreased during treatment. One hypercalcemic patient remained so after 2 weeks of treatment but serum calcium concentration decreased to normal or near normal in the remaining patients. In all patients bone resorption was reduced considerably. The 24-hour urinary calcium
excretion was measured in 4 patients and decreased during treatment. There was a consistent decrease in hydroxyproline excretion in patients studied. The response of serum alkaline phosphatase to the medication varied. There were no consistent changes noted in serum phosphate concentration or renal tubular reabsorption of phosphate. The only side effect noted was mild gastrointestinal disturbance in 1 patient. After treatment with clodronate was discontinued hypercalcemia recurred in all patients. In 3 patients treated for ;;;;19 weeks serum and urinary calcium levels began to return toward pre-treatment values despite treatment. The results suggest that clodronate may be of use in the medical management of hyperparathyroidism, especially in high risk patients or those in whom extensive bone disease suggests the need for preparation before treatment. G.W.K. 2 figures, 2 tables, 23 references
MISCELLANEOUS Low F.ractional Excretion of U :rine Sodium in Acute Renal Failure Due to Sepsis
A. J.
VAZ,
Jacksonville, Florida
Arch. Intern. Med., 143: 738-739 (Apr.) 1983 The fractional excretion of sodium, which is calculated by the formula (urine sodium/plasma sodium) "7" (urine creatinine/plasma creatinine) X 100, has been used to establish the diagnosis of acute renal failure. A value of <1 per cent is considered consistent with pre-renal azotemia or acute glomerulonephritis, while a value of >l per cent is believed to be consistent with acute tubular necrosis or obstructive uropathy. The author reported 2 cases of oliguric acute renal failure owing to sepsis, in which the fractional excretion of sodium was
Nondilated Obstructive Nephropathy J.
H. RASCOFF, C. CHARYTAN,
R. A. GOLDEN, B. S. SPINOWITZ AND Renal Section, Department of Medicine, Booth Memorial Medical Center, Flushing, New York, and Albert Einstein College of Medicine, Bronx, New York
Arch. Intern. Med., 143: 696-698 (Apr.) 1983 The authors report 3 convincing cases of obstructive uropathy in which conventional imaging studies failed to demonstrate dilation of the upper urinary tract. Two patients had known c~rcinoma of the prostate and the ureter al orifices could not be identified at cystoscopy. Sonography and arteriography were used in 1 patient without demonstrating hydronephrosis. Nonetheless, exploration and placement of a nephrostomy resulted in a marked diuresis and return of renal function to virtually normal. In the second patient the ureteral orifices again could not be identified. Sonography and computerized tomography failed to demonstrate evidence of hydronephrosis. Again, in this instance nephrostomy resulted in marked post-
MISCELLANEOUS
The concentrations of metals in the diets are far higher than those of the control meal. Gross organ changes at necropsy on day 81 were not unusual among the present series, at least as compared to the control group. P.R.R. 1 table, 11 references
High-Performance Size-Exclusion Chromatography of 63 Ni-Co:nstituen.ts in Renal Cytosol and Mic.rosomes From 63 NiCb-Treated Rats F.
w.
SUNDERMAN, JR., B. L. K. MANGOLD, S. H. Y. WONG, K. SHEN, M. C. REID AND I. JANSSON, Departments of Laboratory Medicine and Pharmacology, University of Connecticut School of Medicine, Farmington, Connecticut S.
Res. Comm. Chem. Path. Pharm., 39: 477-492 (Mar.) 1983 Workers in nickel refineries have increased risks of cancers of the nose, lung, larynx and, possibly, kidney. They also may suffer nonmalignant respiratory, cutaneous and renal disturbances. Efforts are essential to elucidate the cellular uptake, transport and elimination of nickel (Ni) (11), and the mechanisms of toxicity and carcinogenicity of nickel compounds. This investigation provides the first demonstration of 63 Nicomponents in renal microsomes of 63 Ni-treated rats. Highperformance size-exclusion chromatography on silicone gel bonded macromolecules showed that solubilized, washed microsomes contain 63 Ni in 5 fractions with the same elution profiles as fractions A, B, D, E and F of renal cytosol. In addition, the solubilized microsomes contain a 63 Ni component with high molecular weight (fraction M, >700,000 daltons), which may represent 63 Ni binding to incompletely dissociated aggregates of microsomal proteins and ribonucleic acid. This study provides a rapid, convenient and reproducible technique to fractionate 63 Ni components in tissue extracts, and it demonstrates in vivo binding of 63 Ni to several constituents of renal cytosol and microsomes from 63 Ni Cb-treated rats. P.R.R. 4 figures, 2 tables, 32 references
Drug Treatment of Primary Hypelt'parathy:roidi§m: Use of Clodronate Di§odium
D. L. E.
DOUGLAS, J. A. KANIS, A. D. PATERSON, D. J. BEARD, C. CAMERON, M. E. WATSON, S. WOODHEAD, J. WILLIAMS AND R. G. G. RUSSEL, Department of Human
Metabolism and Clinical Biochemistry, University of Sheffield Medical School, Sheffield, England; Department of Urology, Royal Hallamshire Hospital, Sheffield, England; and Department of Medical Biochemistry, Welsh National School of Medicine, Cardiff, Wales Brit. Med. J., 285: 587-590 (Feb. 19) 1983 The authors studied the effects of clodronate disodium, a specific inhibitor of bone resorption, in 9 patients with primary hyperparathyroidism. Patient age ranged from 61 to 72 years. All patients had normal renal function and had biochemical evidence of hyperparathyroidism. Clodronate was given as a daily single 1 to 3.2 gm. dose before breakfast. In 2 of 3 patients with skeletal pain the pain decreased during treatment. One hypercalcemic patient remained so after 2 weeks of treatment but serum calcium concentration decreased to normal or near normal in the remaining patients. In all patients bone resorption was reduced considerably. The 24-hour urinary calcium
excretion was measured in 4 patients and decreased during treatment. There was a consistent decrease in hydroxyproline excretion in patients studied. The response of serum alkaline phosphatase to the medication varied. There were no consistent changes noted in serum phosphate concentration or renal tubular reabsorption of phosphate. The only side effect noted was mild gastrointestinal disturbance in 1 patient. After treatment with clodronate was discontinued hypercalcemia recurred in all patients. In 3 patients treated for ;;;;19 weeks serum and urinary calcium levels began to return toward pre-treatment values despite treatment. The results suggest that clodronate may be of use in the medical management of hyperparathyroidism, especially in high risk patients or those in whom extensive bone disease suggests the need for preparation before treatment. G.W.K. 2 figures, 2 tables, 23 references
MISCELLANEOUS Low F.ractional Excretion of U :rine Sodium in Acute Renal Failure Due to Sepsis
A. J.
VAZ,
Jacksonville, Florida
Arch. Intern. Med., 143: 738-739 (Apr.) 1983 The fractional excretion of sodium, which is calculated by the formula (urine sodium/plasma sodium) "7" (urine creatinine/plasma creatinine) X 100, has been used to establish the diagnosis of acute renal failure. A value of <1 per cent is considered consistent with pre-renal azotemia or acute glomerulonephritis, while a value of >l per cent is believed to be consistent with acute tubular necrosis or obstructive uropathy. The author reported 2 cases of oliguric acute renal failure owing to sepsis, in which the fractional excretion of sodium was
Nondilated Obstructive Nephropathy J.
H. RASCOFF, C. CHARYTAN,
R. A. GOLDEN, B. S. SPINOWITZ AND Renal Section, Department of Medicine, Booth Memorial Medical Center, Flushing, New York, and Albert Einstein College of Medicine, Bronx, New York
Arch. Intern. Med., 143: 696-698 (Apr.) 1983 The authors report 3 convincing cases of obstructive uropathy in which conventional imaging studies failed to demonstrate dilation of the upper urinary tract. Two patients had known c~rcinoma of the prostate and the ureter al orifices could not be identified at cystoscopy. Sonography and arteriography were used in 1 patient without demonstrating hydronephrosis. Nonetheless, exploration and placement of a nephrostomy resulted in a marked diuresis and return of renal function to virtually normal. In the second patient the ureteral orifices again could not be identified. Sonography and computerized tomography failed to demonstrate evidence of hydronephrosis. Again, in this instance nephrostomy resulted in marked post-