CORRESPONDENCE
Facult6 Xavier Bichat Universit& Paris VII Paris, France
CALCIUM ANTAGONISTS AND AMINOGLYCOSIDE NEPHROTOXICITY To the Editor: Russell and Churchill (Am J Med 1989; 87: 306-315) report on calcium antagonists and ischemic acute renal failure (ARF). We would like to emphasize that calcium antagonists could also be beneficial in the prevention of aminoglycoside-induced ARF. In our laboratory, we have studied the prevention of netilmicin nephrotoxicity by diltiazem in men and in an animal model. Diltiazem (60 mg three times a day for 7 days) in human volunteers could prevent the increase in urinary N-acetylglutamate and the loss of dilution ability induced by netilmicin (4.5 mglkg every day for 7 days) [l]. In a rabbit model of moderate ARF (glomerular filtration rate [GFR] lowered by 50%) induced by netilmicin, we have shown that animals receiving diltiazem in a therapeutic dosage (1 mg/kg three times a day), concurrent with netilmicin (20 mg/kg three times a day) for 5 days, had a GFR similar to that in controls. Diltiazem was protective without altering arterial blood pressure, renal plasma flow, and cortical accumulation or tubular uptake of netilmicin. Netilmicin pharmacokinetics (maximum concentration, area under the curve, distribution volume) were unchanged by diltiazem. Diltiazem might prevent netilmicin toxicity through mechanisms involving glomerular mesangium rather than a selective reduction in afferent and preglomerular resistance [2]. In summary, calcium antagonists appear to prevent aminoglycoside-induced ARF, probably by pathways different from those involved in the prevention of ischemic ARF. Calcium antagonists could be useful in patients undergoing renal transplantation, cardiopulmonary bypass, or resection of aortic aneurysm in whom gram-negative infections, potentially requiring aminoglycoside therapy, are frequently associated with hemodynamically mediated transient reduction in GFR. 0. LORTHOLARY, V. MAHE, F. BLANCHET. C. CARBON,
M.D. M.D. Ph.D. M.D.
INSERM
1. Mahe V, Blanchet F. Sera N. et a/: Drlbazem, a calcrum entry blocker, protects human volunteers agarnst netrlmrcrn nephrotoxrcity (abstr 295). 28th InterscIence Conference on Antimrcrobral Agents and Chemotherapy. Los Angeles, California, 1988. 2. Lortholary 0. Blanchet F, Seta N, Amrrault P. Carbon C. Tubular oarameters bv diltrazem at theraoeuttc dosage agarnst chronic nettlmrctn renal toxicity In rabbits (abstr 294). 29th Interscience Conference on AntImIcrobial Agents and Chemotherapy. Houston, Texas, 1989. Submitted October
10, 1989, and accepted November 14. 1989
PROSPECTIVE TESTING OF FALL RISK INDEX To the Editor: The fall risk index presented by Tinetti et al (Am J Med 1986; 80: 429-434) was prospectively evaluated under the direction of Dr. Charles Beauchamp at the Sioux Falls Veterans Administration Medical Center to test this clinical prediction rule on new patients in a different clinical setting [l]. The incidence and consequences of falls among the elderly continue to be a major concern for all health-care providers, as evidenced by the large number of related articles in medical, nursing, and quality-assurance journals. Accurately predicting patients’ risk of falling from systematic clinical observations should help physicians and other providers identify which patients require interventions to reduce their potential for falls [1,2]. Direct observation by a multidisciplinary team of a sample of 26 male patients was used to collect baseline data as identified in the Tinetti study. Patients were then assigned to one of three risk groups: yes, predicted to fall; 30% chance of falling; not predicted to fall. Reports of falls were reviewed during the following 4 months and data were analyzed by frequency tables and discriminant analysis. Actual occurrences were demonstrated to be consistent with predicted occurrences in the frequency tabulation, and 23 of 26 participants were classified correctly by discriminant analysis. One value of this index is in predicting or identifying patients very likely or unlikely to fall (12 patients in this study). However, the April
1990
The American
majority of patients (14) were grouped in the middle area, in which falls could not be predicted. Another, perhaps more significant, value of the index is in providing reproducible, quantified data sets with which to report falls and intrinsic factors among groups of patients. Although the number of articles related to falls in the elderly continues to grow, there is no standardized method for reporting on patient variables and the effects of various interventions, making comparisons an “apples and oranges” approach. The Tinetti index could fill this void. MARCELLINE
HARRIS,
R.N.,
M.S.
College of Nursing South Dakota State University Brookings, South Dakota 1. Wasson JH, Sox H, Neff R, Goldman L, Clinrcal predtctton rules: applications and methodological standards N Engl J Med 1985. 313: 793-799. 2. Pinhold E. Kroenke K, Hanley J. Kussman M. Twyman P. Carpenter J: Funcbonal assessment of the elderly. a comparison of standard Instruments with clintcal judgment. Arch Intern Med 1987; 147: 48448a. Submitted October 25, 1989, and accepted November 14. 1989
DIAGNOSIS AND TREATMENT OF HIGH-GRADE MYELOMA To the Editor: I read with great interest the recent clinicopathologic conference in which the differential diagnosis of multiple myeloma with transformation versus immunoblastic lymphoma was raised in a patient who developed high-grade malignancy 1.5 years after detection of a monoclonal gammopathy (Am J Med 1989; 87: 577-582). We have recently described “high-grade myeloma” defined by high serum levels of lactic dehydrogenase (LDH) with high-grade lymphoma features including extraosseous disease, renal failure, high µglobulin levels, hypercalcemia, and, most important, a rapidly fatal disease course [l]. Although this syndrome is more prevalent among patients with refractory multiple myeloma, elevated serum LDH levels were also found to confer a poor prognosis among newly diagnosed patients receiving VAD (vincristine-AdriamycinTM-dexamethasone) chemotherapy. We recommended that LDH analysis should become part of the standard myJournal
of Medicine
Volume
88
445
Facult6 Xavier Bichat Universit& Paris VII Paris, France
CALCIUM ANTAGONISTS AND AMINOGLYCOSIDE NEPHROTOXICITY To the Editor: Russell and Churchill (Am J Med 1989; 87: 306-315) report on calcium antagonists and ischemic acute renal failure (ARF). We would like to emphasize that calcium antagonists could also be beneficial in the prevention of aminoglycoside-induced ARF. In our laboratory, we have studied the prevention of netilmicin nephrotoxicity by diltiazem in men and in an animal model. Diltiazem (60 mg three times a day for 7 days) in human volunteers could prevent the increase in urinary N-acetylglutamate and the loss of dilution ability induced by netilmicin (4.5 mglkg every day for 7 days) [l]. In a rabbit model of moderate ARF (glomerular filtration rate [GFR] lowered by 50%) induced by netilmicin, we have shown that animals receiving diltiazem in a therapeutic dosage (1 mg/kg three times a day), concurrent with netilmicin (20 mg/kg three times a day) for 5 days, had a GFR similar to that in controls. Diltiazem was protective without altering arterial blood pressure, renal plasma flow, and cortical accumulation or tubular uptake of netilmicin. Netilmicin pharmacokinetics (maximum concentration, area under the curve, distribution volume) were unchanged by diltiazem. Diltiazem might prevent netilmicin toxicity through mechanisms involving glomerular mesangium rather than a selective reduction in afferent and preglomerular resistance [2]. In summary, calcium antagonists appear to prevent aminoglycoside-induced ARF, probably by pathways different from those involved in the prevention of ischemic ARF. Calcium antagonists could be useful in patients undergoing renal transplantation, cardiopulmonary bypass, or resection of aortic aneurysm in whom gram-negative infections, potentially requiring aminoglycoside therapy, are frequently associated with hemodynamically mediated transient reduction in GFR. 0. LORTHOLARY, V. MAHE, F. BLANCHET. C. CARBON,
M.D. M.D. Ph.D. M.D.
INSERM
1. Mahe V, Blanchet F. Sera N. et a/: Drlbazem, a calcrum entry blocker, protects human volunteers agarnst netrlmrcrn nephrotoxrcity (abstr 295). 28th InterscIence Conference on Antimrcrobral Agents and Chemotherapy. Los Angeles, California, 1988. 2. Lortholary 0. Blanchet F, Seta N, Amrrault P. Carbon C. Tubular oarameters bv diltrazem at theraoeuttc dosage agarnst chronic nettlmrctn renal toxicity In rabbits (abstr 294). 29th Interscience Conference on AntImIcrobial Agents and Chemotherapy. Houston, Texas, 1989. Submitted October
10, 1989, and accepted November 14. 1989
PROSPECTIVE TESTING OF FALL RISK INDEX To the Editor: The fall risk index presented by Tinetti et al (Am J Med 1986; 80: 429-434) was prospectively evaluated under the direction of Dr. Charles Beauchamp at the Sioux Falls Veterans Administration Medical Center to test this clinical prediction rule on new patients in a different clinical setting [l]. The incidence and consequences of falls among the elderly continue to be a major concern for all health-care providers, as evidenced by the large number of related articles in medical, nursing, and quality-assurance journals. Accurately predicting patients’ risk of falling from systematic clinical observations should help physicians and other providers identify which patients require interventions to reduce their potential for falls [1,2]. Direct observation by a multidisciplinary team of a sample of 26 male patients was used to collect baseline data as identified in the Tinetti study. Patients were then assigned to one of three risk groups: yes, predicted to fall; 30% chance of falling; not predicted to fall. Reports of falls were reviewed during the following 4 months and data were analyzed by frequency tables and discriminant analysis. Actual occurrences were demonstrated to be consistent with predicted occurrences in the frequency tabulation, and 23 of 26 participants were classified correctly by discriminant analysis. One value of this index is in predicting or identifying patients very likely or unlikely to fall (12 patients in this study). However, the April
1990
The American
majority of patients (14) were grouped in the middle area, in which falls could not be predicted. Another, perhaps more significant, value of the index is in providing reproducible, quantified data sets with which to report falls and intrinsic factors among groups of patients. Although the number of articles related to falls in the elderly continues to grow, there is no standardized method for reporting on patient variables and the effects of various interventions, making comparisons an “apples and oranges” approach. The Tinetti index could fill this void. MARCELLINE
HARRIS,
R.N.,
M.S.
College of Nursing South Dakota State University Brookings, South Dakota 1. Wasson JH, Sox H, Neff R, Goldman L, Clinrcal predtctton rules: applications and methodological standards N Engl J Med 1985. 313: 793-799. 2. Pinhold E. Kroenke K, Hanley J. Kussman M. Twyman P. Carpenter J: Funcbonal assessment of the elderly. a comparison of standard Instruments with clintcal judgment. Arch Intern Med 1987; 147: 48448a. Submitted October 25, 1989, and accepted November 14. 1989
DIAGNOSIS AND TREATMENT OF HIGH-GRADE MYELOMA To the Editor: I read with great interest the recent clinicopathologic conference in which the differential diagnosis of multiple myeloma with transformation versus immunoblastic lymphoma was raised in a patient who developed high-grade malignancy 1.5 years after detection of a monoclonal gammopathy (Am J Med 1989; 87: 577-582). We have recently described “high-grade myeloma” defined by high serum levels of lactic dehydrogenase (LDH) with high-grade lymphoma features including extraosseous disease, renal failure, high µglobulin levels, hypercalcemia, and, most important, a rapidly fatal disease course [l]. Although this syndrome is more prevalent among patients with refractory multiple myeloma, elevated serum LDH levels were also found to confer a poor prognosis among newly diagnosed patients receiving VAD (vincristine-AdriamycinTM-dexamethasone) chemotherapy. We recommended that LDH analysis should become part of the standard myJournal
of Medicine
Volume
88
445
