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Biomedical subjects

W A Crowell

Publications and source records attributed to W A Crowell.

At least 37 records · Page 2Linked to original sources

Dietary protein intake and the glomerular adaptations to partial nephrectomy in dogs.

After partial nephrectomy (Nx) in rats, a temporal pattern of progressively declining renal function often develops. This pattern has been attributed to the development of glomerular hyperfiltration, hypertension and hypertrophy in remnant nephrons. In rats, dietary protein restriction prevents these adaptive changes in remnant nephrons, thereby preserving renal structure and function. However, long-term studies of the temporal pattern of renal function have failed to identify a consistently progressive deterioration of renal function in partially Nx dogs, and a protective effect of protein restriction has not been apparent in this species. To address these issues in dogs, we evaluated the single nephron adaptations to partial Nx in dogs and the effect of dietary protein restriction on these adaptations. Results of our micropuncture studies in partially Nx dogs indicate that remnant nephrons of dogs exhibit glomerular hyperfiltration (single nephron glomerular filtration rate of 144 +/- 8 vs. 71 +/- 4 nL/min in controls, P less than 0.05), hypertension (glomerular capillary pressure of 75.1 +/- 1.6 vs. 63.2 +/- 1.9 mmHg in controls) and hypertrophy (glomerular volume of 3.54 +/- 0.24 x 10(6) vs. 2.04 +/- 0.05 x 10(6) microns3 in controls, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Beneficial effects of dietary mineral restriction in dogs with marked reduction of functional renal mass.

Although studies in partially nephrectomized rats have identified a progressive nephropathy that is altered by dietary restriction of phosphorus intake, the response of dogs to similar perturbations has not been established. Functional renal mass was reduced by 15/16 in dogs to determine its long-term effects on renal function and to evaluate the effects of two levels of dietary mineral (calcium and phosphorus) intake (0.44% phosphorus/0.57% calcium versus 1.50% phosphorus/1.91% calcium). Following a 3-month stabilization period, dogs were fed either the lower mineral diet (group 1, N = 12) or the higher mineral diet (group 2, N = 12) for 24 months. Loss of renal function with the passage of time was observed in 10 of 12 dogs maintained on the higher mineral diet, with an average decrease in exogenous creatinine clearance of 11.1 +/- 6.3%/month, leading to a survival rate of 33% in this group. Restriction of dietary mineral intake slowed (P less than 0.05) the rate of decline of exogenous creatinine clearance in group 1 to 2.6 +/- 1.1%/month and improved 24-month survival to 75% (P less than 0.01). Deterioration of renal function was associated with renal calcium accumulation and histologic evidence of nephrocalcinosis, tubular atrophy and dilatation, and interstitial fibrosis. These events were more readily apparent in female than in male dogs. A role for glomerulosclerosis was not apparent, and neither glomerular pathology nor glomerular volume was related to the observed decrements in renal function.

Animals↗

Exogenous creatinine clearance as a measure of glomerular filtration rate in dogs with reduced renal mass.

Renal mass was surgically reduced in 78 dogs by uninephrectomy or by combined renal infarction and uninephrectomy. Renal clearance of inulin and renal clearance of exogenous creatinine were determined simultaneously, and the creatinine to inulin clearance (C/I) ratio was calculated. Clearance procedures were performed 2 to 3 months after reduction of renal mass, and were repeated at intervals thereafter. Overall, the C/I ratio was 1.008 +/- 0.007 for 192 determinations, with a highly significant correlation (R2 = 0.994, P less than 0.0001) between creatinine clearance and inulin clearance. There was no significant effect of gender of dogs, time after partial renal ablation, or dietary protein intake on C/I ratios. Degree of renal ablation did not affect C/I ratios. The results indicated that exogenous creatinine clearance is a valid measure of glomerular filtration rate in both male and female dogs with reduced renal mass.

Animals↗

Culture and morphologic features of small intestinal mucosal explants from weaned pigs.

Small intestinal explants from weaned pigs were cultured under a variety of conditions. Explants maintained villus-to-crypt ratio between 1:1 and 1.5:1 for 48 hours. The mucosal epithelium remained well preserved and retained good cellular morphologic features, as determined by light and electron microscopy. Between 48 and 72 hours, considerable mucosal degeneration was evident. Best results were obtained when the explants were cultured on a rocking platform placed in an atmosphere of 95% O2 and 5% CO2, using supplemented RPMI 1640 cell culture medium.

Animals↗

Effect of dietary protein on functional, morphologic, and histologic changes of the kidney during compensatory renal growth in dogs.

Two diets similar in caloric density and mineral content, but markedly different in protein content, were used to study the effects of dietary protein on renal function and morphologic and histopathologic changes in dogs that had functional renal tissue reduced by seven-eights nephrectomy. The effects of moderate protein intake (MPrI = 15% protein; dry-matter basis) and high-protein intake (HPrI = 31% protein; dry-matter basis) were studied for the initial 7 months (period 1 [P1]) after renal mass reduction. Diets were then switched between groups during the following 7 months (period 2 [P2]) to evaluate the effects of increased or decreased protein intake. The HPrI caused significantly (P less than 0.05) greater glomerular filtration rate (GFR) and renal growth than did MPrI during P1. Dogs that maintained HPrI during P1 and MPrI during P2 (group 1) had significant (P less than 0.05) reduction in GFR during P2. Dogs that maintained MPrI during P1 and HPrI during P2 (group 2) had significant (P less than 0.05) improvement in GFR and renal growth during P2. At the end of the study, renal reserve was evaluated in both groups of dogs before and after group 1 was returned to HPrI for 2 weeks. During this 2-week feeding trial, group-1 dogs had marked improvement in renal reserve, relative to group 2, and GFR increased to the terminal P1 values. Results indicate a possible residual benefit from HPrI during the early phase of compensatory renal growth in the form of functional compensatory memory to HPrI. The severity of renal lesions was indistinguishable between dogs of dietary groups during both study phases.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

Suspected familial renal disease in chow chows.

Renal disease was diagnosed in 6 young Chow Chows. Clinical abnormalities included vomiting, polyuria, polydipsia, and weight loss. Common abnormal laboratory findings were azotemia, hyperphosphatemia, hypocalcemia, nonregenerative anemia, and low urine specific gravity. All 6 dogs had similar microscopic renal lesions. characterized by interstitial fibrosis, a population of small glomeruli, and lack of inflammatory cells. A familial basis for the renal disease is suggested because of its development in 4 closely related dogs.

Animals↗

Single-nephron adaptations to partial renal ablation in the dog.

Micropuncture and histological studies were performed in dogs to characterize single-nephron adaptations to partial renal ablation. Dogs underwent sham surgery (group 1, n = 6), three-fourths nephrectomy (group 2, n = 10), or seven-eighths nephrectomy (group 3, n = 6). Single-nephron glomerular filtration rate (SNGFR) was 71.0 +/- 4.2 nl/min in group 1, 132.5 +/- 9.6 nl/min in group 2, and 161.8 +/- 12.4 nl/min in group 3 (P less than 0.05). There were parallel increases in single-nephron glomerular plasma flow rate (GPF), with a mean value of 235.3 +/- 20.1 nl/min in group 1, 442.4 +/- 34.4 nl/min in group 2, and 569.6 +/- 73.7 nl/min in group 3 (P less than 0.05, group 1 vs. groups 2 and 3). Glomerular capillary pressure, estimated from the sum of proximal tubule stop-flow pressure and arterial oncotic pressure, was 63.2 +/- 1.9 mmHg in group 1, 73.5 +/- 2.0 mmHg in group 2, and 77.9 +/- 2.2 mmHg in group 3 (P less than 0.05, group 1 vs. groups 2 and 3). The mean glomerular transcapillary hydraulic pressure gradient (delta P) in group 2 was not different from group 1 (46.8 +/- 1.3 vs. 43.9 +/- 1.8 mmHg, NS); however, it was significantly increased in group 3 (50.0 +/- 1.4 mmHg; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

Influence of copper nutrition on gentamicin nephrotoxicity in rats.

Lipid peroxidation may play a role in the acute nephrotoxicity of gentamicin (GM). Copper (Cu) depletion is associated with reduced activity of certain antioxidant enzymes in tissues, and with kidney lesions and impaired renal function. This study, therefore, investigated the effect of Cu nutrition on GM nephrotoxicity. Weanling male Sprague-Dawley rats were fed Cu adequate or Cu depleted diets for 16 days, then injected intraperitoneally with GM (0-100 mg.kg body weight-1.day-1) for 8 days. GM, but not mild Cu depletion, induced lesions in the kidney and increased plasma urea and urinary excretion of n-acetyl-beta-glucosaminidase. Lower iron in Cu-depleted kidneys and normal Cu, Zn-superoxide dismutase may have prevented additional GM damage during mild Cu depletion.

Animals↗

Pathologic changes and tissue gentamicin concentrations after intravenous gentamicin administration in clinically normal and endotoxemic cats.

Hematologic and serum biochemical values, tissue gentamicin concentrations, and renal pathologic changes were determined in clinically normal and endotoxemic cats given 3 mg of gentamicin/kg of body weight, IV. Endotoxemia was induced by IV administration of 0.5 microgram of Escherichia coli endotoxin/kg of body weight. In experiment 1, 6 cats were given endotoxin. After rectal temperature increased at least 1 degree C, cats were given gentamicin. Blood samples were collected before and at 1 and 3 hours after administration of gentamicin. With the exception of severe leukopenia, other hematologic changes or changes in serum biochemical values were not observed. In experiment 2, 24 cats were allotted to 4 groups and were given gentamicin, endotoxin, gentamicin plus endotoxin, or neither substance. Three hours later, cats were euthanatized, and tissue and body fluid specimens were obtained and were assayed for gentamicin concentration. Kidney specimens were examined microscopically. Endotoxemic cats had more gentamicin in the renal medulla than did control cats, but none of the cats had detectable renal lesions. The possible nephrotoxic synergism between gentamicin and severe endotoxemia and the lack of major differences in gentamicin concentration in extrarenal tissues indicated that the dosage of gentamicin in endotoxemic cats does not have to exceed the dosage recommended for clinically normal cats. A single dose of gentamicin administered IV did not cause renal damage in mildly endotoxemic cats, but nephrotoxicity ascribed to multiple doses of gentamicin in more severely endotoxemic cats needs to be evaluated.

Animals↗

Pharmacokinetic and pathological evaluation of gentamicin in cats given a small intravenous dose repeatedly for five days.

Gentamicin was administered to six cats at a dosage of 3 mg/kg of body weight intravenously every 8 h for five days. Peak and trough serum gentamicin concentrations were measured after each injection. Gentamicin elimination rate and serum half-life were calculated. Serum urea nitrogen, creatinine, biochemistry profile, electrolyte, glucose, total protein, and albumin concentrations were measured daily. Urinalyses were performed before and after the five-day experimental period. The mean +/- SD peak serum gentamicin concentration was 7.19 +/- 1.10 micrograms/mL, and the trough concentration was 0.59 +/- 0.09 microgram/mL. These concentrations are known to be effective against most gentamicin-sensitive bacteria. The mean +/- SD gentamicin elimination rate was 0.0065 +/- 0.0004 min-1. The harmonic mean +/- pseudo standard deviation serum half-life of gentamicin was 107.21 +/- 12.79 min. There were no significant increases (P greater than 0.05) in clinicopathological variables. Microscopic examination of renal sections did not disclose pathological lesions. Signs of vestibular impairment were not observed. A dosage of 3 mg gentamicin/kg given intravenously every 8 h for five days was determined to be safe and to produce therapeutic blood levels in cats.

Animals↗

Acute renal failure in six horses resulting from haemodynamic causes.

Six horses had been admitted to the hospital because of illness other than renal failure; diarrhoea, myositis, abdominal pain and/or suspected bacterial sepsis. Hypotension and disseminated intravascular coagulopathy were frequent findings in the horses. Abnormally high serum creatinine concentration and urine specific gravity of less than 1.022 were found in the horses with acute renal failure. Hyponatraemia and hypochloraemia were the most common abnormal electrolyte findings. Pronounced hyperkalaemia was not found. Variable degrees of tubular necrosis were seen in three of the four horses that had kidney sections submitted for microscopic examination. Renal cortical necrosis occurred in one horse. Intravenous fluid and electrolyte replacement was the most important therapy in those cases that were non-oliguric. Furosemide, mannitol and dopamine were used in horses with oliguria. The prognosis was generally good if the predisposing cause could be corrected and the acute renal failure was not oliguric.

Acute Kidney Injury↗

Lesions in dogs following renal transplantation and immunosuppression.

Renal allografts were transplanted into 20 dogs (12 beagles, eight mongrels) following a prescribed protocol for pre-transplantation blood transfusions and kidney exchange. Immunosuppressive therapy (azathioprine and prednisone) was modified as needed for each dog. Seven of the beagle dogs survived for 1 year and were then euthanized; all other dogs died or were euthanized prior to 1 year post-transplantation. Graft rejection and renal failure were the greatest causes of mortality. Renal lesions which contributed to the death of some animals included renal vein thrombosis, nephrosis, and pyelonephritis. Inflammation of the lower respiratory tract (bronchitis, pneumonia, and pleuritis) was a contributory cause of death in some dogs. Cystitis and ureteritis occurred in almost half of the dogs. Prostatitis was seen in six of the 16 male dogs. Adrenal cortical atrophy, parathyroid gland hyperplasia, and bone marrow hypocellularity were seen in a majority of the dogs which survived 1 year.

Animals↗

Distal renal tubular acidosis and hepatic lipidosis in a cat.

Clinical and laboratory evidence of hepatic failure was found in a chronically anorectic cat. Simultaneous blood and urine pH determinations established a diagnosis of distal renal tubular acidosis. The cat did not respond to treatment. Necropsy revealed distal tubular nephrosis and hepatic lipidosis. The finding of distal renal tubular acidosis in a cat with hepatic lipidosis emphasizes the importance of complete evaluation of acid-base disorders in patients.

Acidosis, Renal Tubular↗

A nephrotic-like syndrome with an associated mesangio-proliferative glomerulopathy in a cow.

A 3-year-old Limousin cow was admitted to the University of Georgia Teaching Hospital with a history of chronic weight loss and diarrhea of more than 1 year's duration. Clinical laboratory findings included proteinuria and hypoproteinemia and were suggestive of a nephrotic-like syndrome. Necropsy findings included generalized edema of the visceral organs and diffuse red glistening foci on the capsular and cut surfaces of the cortex of both kidneys. Microscopically, the kidney had hypercellular and hypersegmented glomeruli, focal glomerulosclerosis, periglomerular fibrosis, and tubular nephrosis. The glomerular hypercellularity was confirmed by electron microscopy to be due to increased mesangial cells.

Animals↗

Effect of induced prostatic infection on semen quality in the dog.

Chronic Escherichia coli prostatitis was induced in 6 dogs, with 5 sham-operated dogs serving as controls. Semen volume and sperm motility, concentration, and appearance were measured 3 times (every other day) before surgery and 3 times during the 3rd and 5th week after surgery. When values for these collections were compared, using a 2-factor analysis of variance, no significant differences (P greater than 0.05) were found. However, the percentage of normal sperm decreased markedly (from 92% to 61% to 64%) in 2 infected dogs because of an increase in primary (from 6% to 32%) or secondary (from 2% to 28%) sperm abnormalities. Testes from both of these dogs were histologically normal.

Analysis of Variance↗

Food and water intake and urine composition in cats: influence of continuous versus periodic feeding.

Twenty healthy, noncastrated, adult male cats had periodic (11 am to 12 am) or continuous (24 hours daily) access to food. With periodic feeding, cats ate less food, drank less water, and produced less urine than when food was available continuously. The composition of urine obtained by cystocentesis at 7:30 am, 3:30 pm, and 10 pm was influenced somewhat by feeding pattern. With periodic feeding, urine pH was lower at 7:30 am and higher at 3:30 pm than it was with continuous feeding. Most mineral concentrations and urine osmolality-specific gravity did not differ with the different feeding schedules. However, when periodic feeding was used, concentrations of magnesium and phosphorus in urine were as high or higher preprandially (7:30 am) than postprandially (3:30 pm). Frequency of urination per 24 hours was not influenced by the feeding schedule, but the time that urination occurred during the 24-hour period was somewhat different. An experimental, high magnesium diet fed to the cats for 200 days caused urethral obstruction in 7 of 10 cats fed periodically and in 7 of 10 cats fed continuously. Cats with obstruction had urinary mineral concentrations similar to concentrations in cats without obstruction, indicating that urinary mineral concentration may not be the only factor relevant to the process of obstruction. Necropsy findings and histologic evaluation of tissues from the cats indicated incidental lesions or abnormalities caused by urethral obstruction, but did not indicate anatomic abnormalities that would have predisposed the cats to obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Gentamicin-associated acute renal failure in the dog.

Gentamicin-associated acute renal failure was diagnosed in 10 dogs. The disease was characterized by a poor prognosis and lengthy hospitalization. Hypoalbuminemia, disorders of potassium homeostasis, proteinuria, hematuria, and cylindruria were common during therapy for renal failure. Fever and dehydration were the most commonly identified potential predisposing factors.

Acute Kidney Injury↗

Kidney graft survival in transfused and nontransfused sibling beagle dogs.

In 6 pairs of sibling Beagle dogs, 1 kidney was exchanged between pairs, and contralateral nephrectomy was done. Previously, one dog of each pair was given blood transfusions from the donor of its allograft. All dogs were given azathioprine and prednisone postoperatively for immunosuppression. Four of 6 dogs given pretransplantation transfusions were healthy 1 year after surgical manipulation was done, and 2 died for reasons other than graft rejection. Of the 6 dogs that were not given pretransplantation transfusions, 3 were healthy after 1 years, but 2 were euthanatized because of graft rejection, and the last was euthanatized because of both graft rejection and intussusception. Other complications in these dogs were leukopenia (7 dogs), interdigital abscesses (2 dogs), urinary infection (3 dogs), and renal vein thrombosis (1 dog). Considering the lack of alternative methods for effective therapy for chronic renal failure in dogs, results of this study seem encouraging for selective use of renal transplantation, clinically. This study supports previous reports which indicated that pretransplantation transfusion enhanced graft survival in dogs.

Animals↗