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Biomedical subjects

D J Chew

Publications and source records attributed to D J Chew.

At least 19 recordsLinked to original sources

Effects of mithramycin on calcium metabolism and bone in dogs.

Mithramycin (0.1 mg/kg) was administered intravenously to eight Beagle dogs on days 0 and 7 to determine its effects on calcium and phosphorus metabolism, serum parathyroid hormone concentration, osteoclastic bone resorption, and serum biochemical and hematologic parameters. Ionized calcium concentration was paradoxically increased on day 1 and decreased on day 8 in association with an increased serum parathyroid hormone concentration. Serum phosphorus concentration was decreased on days 1 and 2. Osteoclastic bone resorption in iliac cancellous bone was significantly decreased on day 8. There were mild increases in serum alkaline phosphatase (days 1, 2, 4, 8, 9), aspartate aminotransferase (day 9), and gammaglutamyl transpeptidase (days 7, 9) activities. Platelet numbers were increased on days 7 through 13, and packed red blood cell volumes were mildly decreased. This investigation demonstrates that two doses of mithramycin can be administered safely to dogs and may inhibit bone resorption in diseases associated with increased osteoclastic bone resorption, such as humoral hypercalcemia of malignancy.

Animals

Parathyroid hormone (PTH)-related protein, PTH, and 1,25-dihydroxyvitamin D in dogs with cancer-associated hypercalcemia.

Circulating N-terminal PTH-related protein (PTHrP), N-terminal PTH, and 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations were measured in normal dogs and dogs with cancer-associated hypercalcemia (CAH), parathyroid adenomas, and miscellaneous tumors. PTHrP was undetectable (less than 1.8 pM) in normal dogs and increased in dogs with CAH due to adenocarcinomas derived from apocrine glands of the anal sac (44.9 +/- 27 pM), lymphoma (8.3 +/- 4.4 pM), and miscellaneous carcinomas (13.3 +/- 11.4 pM). The PTHrP concentration decreased in dogs with lymphoma and anal sac adenocarcinomas after successful treatment of CAH. The PTHrP concentration had a significant linear correlation with total serum calcium in dogs with anal sac adenocarcinomas and hypercalcemia, but not in dogs with lymphoma and hypercalcemia. Serum N-terminal PTH concentrations were usually in the normal range (12-34 pg/ml) for all groups of dogs except dogs with parathyroid adenomas (83 +/- 38 pg/ml). The serum PTH concentration increased after successful treatment of CAH. Serum 1,25-(OH)2D concentrations were decreased, normal, or increased in dogs with CAH, and 1,25-(OH)2D levels decreased after treatment of CAH. In summary, circulating concentrations of PTHrP are consistently increased in dogs with CAH, and PTHrP appears to play an important role in the induction of hypercalcemia.

Adenoma

Nephrocalcinosis caused by hyperparathyroidism in progression of renal failure: treatment with calcitriol.

Nephrocalcinosis is accepted to contribute to the progression of renal failure. We have reviewed evidence that nephrocalcinosis is caused directly by the excess parathyroid hormone produced in renal disease. Evidence that hyperparathyroidism in uremic patients results from calcitriol deficiency and the mechanisms by which this comes about have been discussed. We have shown that renal secondary hyperparathyroidism can be eliminated or substantially reduced without increasing blood calcium using a low-dosage regimen of calcitriol. Decreasing PTH concentrations to or near normal alleviates this hormone's toxicity to many organs, including the kidneys. Potential benefits for the uremic patient include an increase in the quality and length of life. Calcitriol treatment provides a powerful means to reduce PTH concentration in uremic patients that may not be achieved with other methods. Further prospective clinical studies of uremic dogs and cats are warranted to document preservation of renal function and histology during calcitriol treatments.

Animals

Clinical and metabolic findings in dogs with chronic renal failure fed two diets.

Exogenous creatinine clearance, urinary electrolyte excretions, calcium and phosphorus balance, serum cholesterol concentration, arterial blood pressure, and body weight were evaluated in dogs with chronic renal failure that were fed 2 commercial diets. Nine dogs ranging in age from 1 to 15 years were identified as having mild to moderate chronic renal failure (CRF, exogenous creatinine clearance = 0.5 to 2.13 ml/kg of body weight/min). These dogs and a group of 10 clinically normal controls were fed a diet containing 31% protein for 8 weeks at which time hematologic and biochemical evaluations and clearance studies were performed. All dogs then were fed a phosphorus-restricted diet containing 16% protein and then reevaluated after 8 weeks. The dogs in this study had hematologic and biochemical abnormalities typical of CRF. Urine absolute and fractional excretion of electrolytes was higher in dogs with CRF than in controls and was affected by diet. Serum cholesterol concentration was higher in dogs with CRF and increased in those dogs after feeding the low protein diet. Changes in dietary sodium intake did not affect arterial blood pressure. The phosphorus-restricted diet did not affect serum amino terminal parathyroid hormone concentration in either group. Control dogs lost body weight, whereas dogs with CRF gained weight when fed the low protein diet. We concluded that dogs with mild to moderately severe CRF have the same biochemical abnormalities and response to dietary restriction of protein and phosphorus as has been previously reported in dogs with experimentally induced CRF. Restriction of dietary sodium may not decrease arterial blood pressure in some dogs with CRF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed

Amino acid profiles in dogs with chronic renal failure fed two diets.

Amino acid profiles and serum albumin and serum total protein concentrations were evaluated in dogs with renal disease. Nine dogs ranging in age from 1 to 15 years were identified as having mild to moderate chronic renal failure (CRF; exogenous creatinine clearance, 0.5 to 2.13 ml/kg of body weight/min). These dogs and a group of 10 clinically normal control dogs were fed a diet containing 31% protein for 8 weeks, at which time serum and urine amino acid assays and clearance studies were performed. All dogs then were fed a diet containing 16% protein for 8 weeks and then reevaluated. Chronic renal failure was associated with mild abnormalities in serum concentrations of amino acids. When fed the higher protein diet, dogs with CRF had lower serum concentrations of glutamine, leucine, proline, and serine and higher serum concentrations of cystathionine and 3-methylhistidine than clinically normal control dogs. When fed the low protein diet, dogs with CRF had lower serum serine concentrations and higher serum concentrations of cystathionine, phenylalanine, and 3-methylhistidine. Urine excretion of amino acids in all dogs on both diets was low, and dogs with CRF had lower renal clearances of 3-methylhistidine than control dogs. There were no significant differences in concentrations of serum albumin and total solids between either group, regardless of diet. We concluded that dogs with mild to moderately severe CRF have mild abnormalities of serum free amino acid concentrations, but renal conservation of essential amino acids is not impaired.

Amino Acids

Cystinuria in a cat.

A 10-month-old male Siamese cat with dysuria was determined to have cystine crystalluria. Many small calculi composed entirely of cystine were found in the urinary bladder. Measurement of serum and urine amino acids and calculation of fractional reabsorption of amino acids indicated reabsorption defects for cystine, ornithine, lysine, and arginine. Urinary acidification, fractional reabsorption of glucose, and fractional reabsorption of electrolytes were normal. Diagnoses of cystinuria and cystine urolithiasis were made on the basis of low fractional reabsorption of cystine and dibasic amino acids and the detection of cystine calculi in the urinary bladder.

Absorption

Effect of sodium bicarbonate infusion on serum osmolality, electrolyte concentrations, and blood gas tensions in cats.

The effects of single IV injections of sodium bicarbonate (0.5 mEq/kg of body weight, 1 mEq/kg, 2 mEq/kg, and 4 mEq/kg) on serum osmolality, serum sodium, chloride, and potassium concentrations, and venous blood gas tensions in 6 healthy cats were monitored for 180 minutes. Serum osmolality increased and remained significantly (P less than 0.05) increased for 120 minutes in cats given 4 mEq of sodium bicarbonate/kg. Serum sodium was increased significantly (P less than 0.05) for 30 minutes in cats given 4 mEq of sodium bicarbonate/kg. Serum sodium decreased and remained significantly (P less than 0.05) decreased for 120 minutes in cats given 1 g of 20% mannitol/kg, and serum osmolality was significantly (P less than 0.05) decreased at 30 and 60 minutes. Serum chloride decreased significantly (P less than 0.05) for 10 minutes in cats given 1 mEq of sodium bicarbonate/kg, and was significantly decreased for 30 minutes in cats given 2 mEq and 4 mEq of sodium bicarbonate/kg. Serum chloride decreased and remained significantly (P less than 0.05) decreased for 30 minutes in cats given 1 g of 20% mannitol/kg. Serum sodium and serum osmolality did not change significantly (P less than 0.05) in cats given 4 ml of 0.9% sodium chloride/kg. Serum potassium decreased significantly (P less than 0.05) for 10 minutes in cats given 1 mEq of sodium bicarbonate/kg, and for 120 minutes in cats given 2 mEq/kg or 4 mEq/kg. There was a significantly (P less than 0.05) greater decrease in serum potassium that lasted for 30 minutes after given sodium bicarbonate at the dosage of 4 mEq/kg, compared with other dosages given.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Polycystic kidney disease in a family of Persian cats.

A 6-year-old Persian cat was determined to have polycystic kidney disease (PKD). Because of 3 previous clinical reports of PKD in Persian cats, the offspring were examined by use of ultrasonography, which provided evidence of PKD in 3 of the 4 offspring. Because of the genetic transmission of this disease, breeders should be advised not to breed PKD-positive Persian cats.

Animals

Renal excretion of creatinine, electrolytes, protein, and enzymes in healthy sheep.

Urinary indices of renal function and damage were measured in 6 healthy, mature ewes over a 48-hour period. Endogenous creatinine clearance, total and fractional electrolyte excretion rates, protein excretion, urine volume, and urine gamma-glutamyltransferase and beta-glucuronidase activities were measured. Significant variations in the excretion rates of creatinine, electrolytes, and protein were not found between intervals within the 48-hour urine collection period. Total urinary electrolyte excretion rates were significantly (P less than 0.001) correlated with fractional electrolyte excretion rates normalized for creatinine concentration; however, coefficient of determination was low.

Animals

Enzymuria as an index of renal damage in sheep with induced aminoglycoside nephrotoxicosis.

Acute nephrotoxicosis was induced in ewes by daily SC administration of gentamicin. Activity of 3 urine enzymes, gamma-glutamyltransferase (GGT), beta-N-acetylglucosaminidase (AGS), and beta-glucuronidase (GRS), were measured during the development of aminoglycoside nephrotoxicosis. Measurements from timed, volume-measured urine samples were performed on days 0, 7, and 8. Measurements from urine samples obtained without volume measurement (spot samples) were performed daily. Urine GGT and AGS activities were high 3 days prior to detection of high serum creatinine concentration and 1.5 days before the appearance of casts in the urine sediment; values consistently remained in the abnormal range until termination of the study. High urine GRS activity was inconsistent and transient; serum GGT activity did not change during the course of the study. Urine GGT and AGS activities expressed as total excretion per unit time and body weight, enzyme activity per unit volume, and as ratio of urine enzyme activity to urine creatinine concentration were strongly correlated. Urine GGT and AGS, but not GRS activities, are suitable indicators of renal tubular cell damage in sheep with aminoglycoside nephrotoxicosis. Urine GGT and AGS activities indicate cellular changes occurring several days prior to the first indications of renal functional change.

Acetylglucosaminidase

Early effects of ethylene glycol on the ultrastructure of the renal cortex in dogs.

A sublethal dose of ethylene glycol was administered orally to 3 groups of dogs; dogs of a control group were given distilled water instead. Renal cortical biopsy samples were obtained from dogs of experimental and control groups at various times after treatment. Tissue was examined by use of light microscopy and transmission electron microscopy. In dogs of the control group, the light and electron microscopic appearances of tissue were within normal limits at all sample collection hours. In dogs of the experimental groups, renal corpuscular structure remained within normal limits by use of light and electron microscopy throughout the study, though morphologic change was seen in other structures of the cortex. Light microscopic lesions first appeared at 12 hours, and were similar to those reported in the literature. Ultrastructural lesions were first observed in the 5-hour samples, and similar to the light microscopic lesions, were most common in the proximal convoluted tubules (PCT). Initial PCT cellular changes included vacuolization of cells and distention of the parabasal extracellular spaces; PCT cellular lesions seen in later-hour samples included formation of apical buds and cellular rupture. Internalization or sloughing of the PCT brush border was not observed. Distal convoluted tubules (DCT) were frequently dilated and/or packed with cellular debris. A few DCT cells had degenerative or necrotic changes. In PCT and DCT, abnormal cells were frequently flanked by normal or nearly normal cells. During later hours, a few cells with types of changes first observed in early hours continued to be observed, implying ongoing response of cells to the toxin.

Animals

Urinary indices of renal function in sheep with induced aminoglycoside nephrotoxicosis.

Aminoglycoside nephrotoxicosis (AGNT) was induced in ewes by daily SC administration of gentamicin. Changes in urinary indices of renal function during the development of AGNT are reported. Measurements from timed, volume-measured urine samples were made on days 0, 7, and 8 and included creatinine clearance, total excretion (TE) rates of electrolytes (Na, K, Cl, P) and urine volume. Measurements from free-catch urine samples (without volume measurement) were made daily and included fractional excretion (FE) rate of electrolytes, urine osmolality, and urine-to-serum osmolality and urine-to-serum creatinine ratios. With the onset of AGNT, FE rates of Na, K, Cl, and P- increased many fold above baseline values (200x, 4 to 5x, 6 to 9x, and 70 to 95x, respectively, on days 7 and 8), indicating decreased tubular reabsorption or increased tubular secretion. The increased FE rates were not representative of increases in total electrolyte excretion rates. The total excretion of Na (TENa) was mildly increased, TEK was decreased, TECl was unchanged, and TEP was significantly increased on days 7 and 8. Abnormal urinalysis results, glucosuria, and increased FEP preceded appreciable increase in serum creatinine concentration. Other abnormal urinary indices of renal function coincided with or followed the increase in serum creatinine concentration. Urinary indices may help characterize renal function associated with the disease state, but did not provide early indication of AGNT.

Acute Kidney Injury

Peritoneal dialysis in dogs and cats: 27 cases (1976-1987).

The records of 25 dogs and 2 cats treated with peritoneal dialysis during an 11-year period were evaluated. The indications for peritoneal dialysis were acute renal failure in 21 animals, chronic renal failure in 5 animals, and azotemia of undetermined cause in 1 animal. Peritoneal dialysis resulted in a significant (P less than 0.05) decrease in serum urea nitrogen concentration in 19 of the dogs and a significant (P less than 0.05) decrease in serum creatinine in 20 dogs. The most common complication of peritoneal dialysis was hypoalbuminemia (11 animals affected). Other common complications were dialysate retention/catheter obstruction (8 animals), peritonitis (6 animals), hypochloremia (6 animals), and subcutaneous leakage of dialysate (6 animals). Twelve dogs and 2 cats died during treatment, 6 dogs were euthanatized, and 1 dog was lost to follow-up evaluation. The remaining 6 dogs survived and were discharged from the hospital after successful peritoneal dialysis. On the basis of the results of this study, the authors concluded that peritoneal dialysis, although associated with a high complication rate, was a successful technique for reducing azotemia in dogs with acute and chronic renal failure. Survival rates were poor because of the severity of the underlying renal diseases.

Acute Kidney Injury

Hypercalcemia.

Elevated serum calcium occurs relatively uncommonly in dogs and rarely in cats. Hypercalcemia can serve as a marker of disease that enables diagnosis but may also contribute to development of lesions and the clinical signs of disease. Specific clinical signs do not necessarily accompany hypercalcemia, and its presence will frequently be unsuspected. Fortuitous hypercalcemia is often discovered after a review of serum biochemical profile results. This article emphasizes malignancy-associated hypercalcemia and the emergence of cholecalciferol rodenticide toxicity as an important cause of hypercalcemia, as well as its treatment.

Animals

Effect of sodium bicarbonate infusions on ionized calcium and total calcium concentrations in serum of clinically normal cats.

The effects of sodium bicarbonate (0.5 mEq/kg of body weight, 1.0 mEq/kg, 2.0 mEq/kg, and 4.0 mEq/kg) on ionized and total calcium concentrations were determined in clinically normal cats. Also, serum pH, whole blood pH, and serum albumin, serum total protein, and serum phosphorus concentrations were measured. Intravenous administration of sodium bicarbonate to awake cats decreased serum ionized calcium and serum total calcium concentrations. All dosages of sodium bicarbonate were associated with significant decreases of serum ionized calcium concentration. This effect lasted for greater than 180 minutes when cats were given 2.0 mEq/kg or 4.0 mEq/kg. When cats were given 4 mEq of sodium bicarbonate/kg, serum ionized calcium concentration was significantly decreased, compared with that when cats were given lower doses, but only at 10 minutes after infusion. After sodium bicarbonate infusion, serum total calcium concentration, measured by ion-specific electrode and colorimetry, was lower than baseline values at most of the times evaluated. Decreases in serum ionized calcium and serum total calcium concentrations can be attributed only in part to an increase in serum or whole blood pH and to a decrease in serum protein concentration. Serum total calcium concentrations measured by ion-specific electrode and by colorimetry were positively correlated, but the variability was high. Only 44% of the variability in serum ionized calcium concentration could be predicted when serum total calcium, albumin, total protein, phosphorus, and bicarbonate concentrations and pH were considered.

Animals

Acute hypocalcemia associated with infarction of parathyroid gland adenomas in two dogs.

Two dogs were examined because of anorexia, lethargy, muscle tremors, weakness, and seizures that were associated with an acute onset of hypocalcemia. Both dogs had histories of chronic hypercalcemia. Examination of the parathyroid glands revealed infarction of focal parathyroid adenomas, with atrophy of the remaining parathyroid glands. It was concluded that the acute onset of hypocalcemia was caused by infarction of functional parathyroid adenomas that were previously responsible for the cause of persistent hypercalcemia. Infarction of a parathyroid adenoma should be included in a list of differential diagnoses of acute hypocalcemia in the dog, especially if hypercalcemia has been diagnosed previously.

Adenoma