Biomedical subjects
Publications and source records attributed to R D Adelman.
Hypertension in the neonate usually is associated with renal vascular and parenchymal disease or with chronic lung disease. Antihypertensive medications effectively lower blood pressure and often over time may be discontinued; however, significant structural or functional renal abnormalities may persist.
The nephrotoxicity of the aminoglycoside amikacin sulfate was evaluated in an open, controlled study of newborns with presumed neonatal sepsis. One hundred twelve neonates were randomly allocated to receive either amikacin-ampicillin or mezlocillin, a semisynthetic penicillin. Neonates receiving amikacin, in contrast to those receiving mezlocillin, showed significant nephrotoxicity as evidenced by a delayed postnatal fall in mean serum creatinine level (82 to 80 mumol/L [0.93 to 0.90 mg/dL] vs 84 to 72 mumol/L [0.95 to 0.82 mg/dL]) and a delayed postnatal rise in mean creatinine clearance per kilogram of body weight (12% vs 38%). Furthermore, 40% of neonates receiving amikacin-ampicillin compared with 19% of neonates receiving mezlocillin had a decline in creatinine clearance (greater than 25%). There was no relationship between amikacin nephrotoxicity and either peak or trough amikacin levels. In summary, in a controlled study of the use of amikacin and mezlocillin in neonates, the combination of amikacin and ampicillin proved more nephrotoxic to the newborn kidney.
Twelve neonates with hypertension have been followed for a mean of 5.75 years. At onset of hypertension, mean peak blood pressure was 159/99 mm Hg. Ten infants had umbilical artery catheters, 9 placed above the origin of the renal arteries. Radionuclide renal scan and/or angiography demonstrated renovascular disease, primarily renal artery thrombosis, in 11 infants. One-third of infants were asymptomatic, one-third had normal urinalyses and two-thirds had elevated peripheral plasma renin activities. Blood pressure normalized with medical therapy in all infants and remained normal when therapy was discontinued. Ten infants have normal creatinine clearances on follow-up but 5/11 have unilateral renal atrophy. Radionuclide scans have remained abnormal, even in infants without renal atrophy. In summary, neonatal renovascular hypertension is frequently secondary to renal artery thrombosis, associated with umbilical artery catheterization. Blood pressure usually normalizes with conservative medical management and remains normal off medications. Persistent abnormalities in renal size and function are common.
The nephrotoxicity of the aminoglycoside gentamicin was evaluated in an open, controlled study of newborn infants randomly allocated to receive either combination drug therapy with gentamicin and ampicillin or single drug therapy with mezlocillin for treatment of presumed neonatal sepsis. There were no significant differences in initial clinical characteristics between the groups. Neonates receiving gentamicin, in contrast to those receiving mezlocillin, had significant nephrotoxicity manifested by a smaller postnatal fall in mean serum creatinine concentration (-9%, P NS vs -21%, P less than 0.005, respectively) and a diminished postnatal rise in mean creatinine clearance (+ 21%, P NS vs + 51%, P less than 0.01, respectively). In neonates with a fall in creatinine clearance, the mean decline was significantly greater in those receiving gentamicin (44% vs 20%, P less than 0.01). There was no relationship between the incidence of gentamicin nephrotoxicity and either peak or trough gentamicin levels. For treatment of presumed neonatal sepsis, gentamicin proved more nephrotoxic than mezlocillin.
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We describe seven infants who developed renal calcification and bone demineralization following furosemide therapy with average daily doses of as little as 0.75 mg/kg per day. Renal calcifications were present in all seven cases and were more readily detected with ultrasonography than with plain films. Renal calculi were seen in four patients, sonographically demonstrated as echogenic foci in the dependent portion of the collecting system, usually accompanied by acoustic shadowing. One patient developed nephrocalcinosis, sonographically observed as echogenic medullary pyramids plus punctate, shadowing parenchymal calcifications. In two patients the location of the calcification could not be determined.
Systolic blood pressure and heart rate were measured in beagle puppies from 1 week to 6 months of age. A significant increase in blood pressure and decrease in heart rate occurred with growth. These changes are qualitatively similar to those observed in young infants and children. The beagle puppy may be a useful animal model for the study of normal and abnormal maturational changes in blood pressure and heart rate and for the evaluation of pharmacologic agents currently used in the treatment of cardiovascular disease in the growing and developing infant.
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To evaluate whether abnormal body composition in uremia is a consequence of undernutrition from poor food intake, body fluid compartments and individual organs were measured in moderately uremic (5/6th nephrectomy) and pair fed control rats and in a second group of moderately uremic and control rats on two levels of dietary protein: 43% (HP) and 18.5% (LP). Uremic rats in both groups had significantly increased total body water (TBW) and extracellular water (ECW) and decreased total body solids (TBS). Heart weight in uremic rats was significantly increased, whereas weight of muscle, brain, adrenal, and fat free liver, as a percent of body weight, did not differ from control rats. There were no differences between uremic rats on HP and LP diets in TBW, ECW, TBS or in heart weight and muscle weight. Uremic rats on HP had increased kidney and liver weights. These data demonstrate abnormal body composition in a rat model of moderate uremia. Changes observed appear to be primarily a consequence of uremia per se rather than of undernutrition or level of dietary protein.
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