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Biomedical subjects

R L Chevalier

Publications and source records attributed to R L Chevalier.

At least 109 records · Page 6Linked to original sources

Fetal expression of the angiotensinogen gene.

To determine whether the angiotensinogen (Ao) gene is expressed in multiple organs of the fetal rat and the changes associated with maturation, fetal (15-20 days of gestation), newborn (1-10 days old), and adult (90 days old) rat tissues were subjected to Northern analysis and hybridization with a full length Ao complementary DNA (cDNA). Whereas Ao messenger RNA (mRNA) was undetectable in fetal livers, Ao sequences were readily detectable 1 h after birth and reached a peak at 24 h of birth. Levels remained elevated at 5 and 10 days after birth to decrease slightly at 90 days of postnatal life. Poly A+ enriched liver RNA was subjected to a similar analysis demonstrating that fetal liver Ao mRNA levels were 50-fold less than the corresponding adult levels. In contrast to the finding in the fetal liver, Ao mRNA was found in fetal brown fat, brains, and kidneys. We conclude that 1) Expression of the Ao gene is developmentally regulated in a tissue-specific manner; 2) Unlike the adult animal, the liver may not be the primary source of Ao in the fetus; 3) Alternate sources of Ao synthesis include fetal brown fat, brain, and kidneys.

Adipose Tissue, Brown↗

Intrarenal dopamine-1 receptors control renal function.

Dopamine receptors are classified to DA-1 and DA-2 and are characterized in renal tissue by radioligand binding and by the response of renal adenylate cyclase to dopaminergic agonists and antagonists. DA-1 receptors are localized in the renal tubules, the medial layer of renal microvessels, and the juxtaglomerular apparatus. DA-1 receptor stimulation causes dilation of renal, mesenteric, coronary, and cerebral vessels. In the present study, we tested the hypothesis that dopamine is a paracrine substance in the control of renal function. We employed a potent specific DA-1 receptor antagonist, SCH, to evaluate the role of intrarenal DA-1 receptor in the maintenance of renal function. Intrarenal DA-1 receptor blockade with SCH caused a highly significant dose-dependent antidiuresis and antinatriuresis, and decreased FENa. A rebound diuresis and natriuresis above control values were observed after cessation of DA-1 receptor blockade. There were no changes in renal hemodynamic function during DA-1 receptor blockade. These results strongly suggest that the antinatriuresis and antidiuresis induced by DA-1 receptor blockade are mediated by an action at the renal tubule. The infusion rate of SCH administered intrarenally was sufficiently low to produce no measurable systemic effects including PRA, PAC, and MAP. Thus, these results can be interpreted as due to intrarenal DA-1 blockade. In summary, we have demonstrated that renal excretory function is highly sensitive to DA-1 receptor blockade within the kidney and appears to be mediated by renal tubular events. This study provides strong evidence that DA-1 receptors play a physiological role in the control of renal function.

Animals↗

Pathologic significance of nephromegaly in pediatric disease.

Ultrasonic renal volume and length measurements are easily performed in pediatric patients. Increases in volume over the normal level provide a potentially attractive method of assessing the severity and progression or regression of renal diseases. However, an analysis of data on 59 children with clinical renal disease and nephromegaly did not demonstrate any correlation with severity of the disease. We conclude that increases in renal length and volume in pediatric patients may indicate the presence of disease but not its severity.

Adolescent↗

Fetal expression of muscle-specific isoactins in multiple organs of the Wistar-Kyoto rat.

Actin, a cytoskeletal and contractile protein, is expressed in six different isoforms that exhibit striking specificity. No studies have considered the muscle-specific actin expression in multiple organ systems in the intact fetus. Using a monoclonal antibody (B4) which reacts specifically with the isoactins of the smooth and skeletal muscle our immunohistochemical study examined whole fetal body sections to follow the development of actin expression throughout the last third of gestation in the Wistar-Kyoto rat. B4 staining was exclusively localized to muscle, confirming its high specificity and its usefulness for studying the ontogeny of muscle-specific isoactins. At 15 days of gestation, B4 staining was detected in the heart, the thoracic aorta and the skeletal muscle of the chest wall. The distribution and intensity of staining in the heart were initially higher than in the aorta or skeletal muscle and remained unchanged throughout the remainder of gestation, suggesting that the maturation of cardiac actin expression is well developed, although not fully completed before birth. Expression of muscle-specific actins in skeletal muscle was age-dependent and correlated with the maturational changes of muscle cell precursors. B4 staining in the fetal kidney was not apparent until day 20 of gestation and was localized to the inner cortical vessels. in association with the most mature nephrons, suggesting a centrifugal maturation of the intrarenal vasculature. The intensity of B4 staining in most tissues including bronchi, bowel, diaphragm, chest wall muscle and peripheral and pulmonary arteries increased by the end of gestation.

Actins↗

Rapid correction of acute salt poisoning by peritoneal dialysis.

A 12-month-old girl with end-stage renal disease secondary to primary oxalosis was erroneously given an overdose of sodium chloride (400 mEq NaCl over 12 h) to treat hyponatremia. She became lethargic and hypotonic with signs of intracellular dehydration, and laboratory values revealed severe hypernatremia and hyperchloremia. Since hypernatremia was acute and development of intracellular idiogenic osmoles was presumably minimal, serum sodium was lowered rapidly over 14 h by hourly peritoneal dialysis using a commercial dialysate. This method of treatment proved to be safe and the patient survived without any short or long-term neurological sequelae.

Female↗

Percutaneous transluminal angioplasty for renovascular hypertension in children.

Percutaneous transluminal angioplasty (PTA) has been developed over the past 8 years as an alternative to reconstructive surgery for renovascular hypertension. We report three cases and review the use of PTA in children with renal artery stenosis. At least 37 cases of PTA have been reported in patients whose ages ranged from 1.3 to 17 years (mean 10 years). Of these, 10 had fibromuscular dysplasia; 13 unspecified unilateral renal artery stenosis; 4 bilateral stenosis; 4 neurofibromatosis; 4 renal transplant; 1 atherosclerosis; and 1 postsurgical stenosis. Nine of 10 patients with fibromuscular dysplasia were cured and 3 of 4 with renal transplant arterial stenosis were cured or improved. There were 11 failures of PTA, including all 4 patients with neurofibromatosis and 1 with transplant arterial stenosis. We conclude that PTA is the treatment of choice for children with hypertension due to fibromuscular dysplasia and should be attempted for stenosis of the transplanted renal artery. Other lesions resulting in renal artery stenosis may not be as amenable to dilation and should be considered on an individual basis.

Adolescent↗

Endogenous prostaglandins modulate autoregulation of renal blood flow in young rats.

After uninephrectomy in the young rat, renal blood flow (RBF) increases at normal renal perfusion pressure (RPP) but not at reduced RPP. To evaluate the role of endogenous prostaglandins on these effects, RBF was measured during reduction in RPP in rats that were uninephrectomized within 1 wk of age and studied at 33-41 days of age. After acute cyclooxygenase inhibition, autoregulation improved; RBF was unchanged at normal RPP but increased at lower pressures with concomitant decrease in renal venous plasma renin activity (PRA). Prostaglandin inhibition also improved autoregulatory efficiency in acutely uninephrectomized and sham-operated young rats. Infusion of a thromboxane synthesis inhibitor had no effect on the pressure-flow relationship or on PRA, whereas angiotensin converting enzyme inhibition increased RBF at all measured RPP without affecting autoregulation. We conclude that increased RBF at normal RPP in the uninephrectomized young rat is not maintained by increased prostaglandin synthesis or decreased thromboxane- or angiotensin-dependent vasoconstriction. However, by maintaining increased vasoconstriction at reduced RPP, prostaglandin-dependent renin release reduces autoregulatory efficiency in the young rat.

Animals↗

Morphologic correlates of renal growth arrest in neonatal partial ureteral obstruction.

To investigate the morphologic correlates of decreased renal blood flow and growth arrest resulting from chronic partial ureteral obstruction in the neonate, guinea pigs were subjected to unilateral ureteral constriction within the first 2 days of life and were studied at 3 and 8 wk of age. Severity of histologic changes in the obstructed and intact contralateral kidney was assessed by light microscopy. Morphometric glomerular measurements were made using a computerized tracing device. Since contralateral nephrectomy or administration of angiotensin converting enzyme inhibitor (enalapril) result in increased blood flow to the obstructed kidney, morphologic changes were also examined in separate groups of animals subjected to these maneuvers, and were compared to appropriate controls. Ipsilateral chronic partial ureteral obstruction resulted in decreased glomerular volume (p less than 0.0001) and increased glomerular crowding associated with tubular dilatation and progressive glomerular sclerosis, tubular atrophy, and interstitial fibrosis. The intact contralateral kidney underwent hypertrophy with increase in glomerular volume (p less than 0.0001) and decreased glomerular density. Contralateral nephrectomy prevented the decrease in glomerular volume in the obstructed kidney and resulted in decreased glomerular density and reduced tubular atrophy at 3 wk of age. Enalapril prevented the decrease in glomerular volume at 3 wk of age, but glomerular and tubular changes progressed and were unaffected by enalapril at 8 wk. Left kidney glomerular volume was directly related to renal blood flow (r = 0.71, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Increased renal cortical echogenicity in pediatric renal disease: histopathologic correlations.

Retrospective comparisons between sonographic renal cortical echogenicity and the results of renal biopsies were made for 65 pediatric patients ranging in age from neonate to 18 years. There was a positive correlation between an increase in renal cortical echoes and interstitial infiltration as well as with glomerular obsolescence, tubular atrophy, and vascular changes. Since the sonographic changes were heterogeneous in origin, they are not specific. The sonographic findings also correlated positively with the clinical severity of disease. However, the heterogeneous origins of the sonographic finding and the absence of strong correlations indicate that gray-scale sonography cannot act as a prognostic index of the type or severity of disease in pediatric patients.

Adolescent↗

Contribution of endogenous vasoactive compounds to renal vascular resistance in neonatal chronic partial ureteral obstruction.

To evaluate the relative contribution of endogenous vasoactive compounds to maintenance of increased renal vascular resistance in neonatal obstructive nephropathy, cardiac output and renal blood flow were measured using radioactive microspheres in 25 +/- 3 day-old guinea pigs subjected to unilateral partial ureteral constriction within the first two days of life. Mass and renal blood flow of the obstructed kidney were significantly lower than those of the contralateral kidney. Following a control period, thromboxane synthesis was blocked by infusion of OKY-046, after which prostaglandin synthesis was inhibited by indomethacin. In a separate group of animals, angiotensin converting enzyme inhibitor, MK-422, was infused before or after administration of OKY-046. While neither OKY-046 nor indomethacin had a consistent effect on vascular resistance, infusion of MK-422 resulted in selective reduction of renal vascular resistance of the obstructed kidney compared to resistance in the intact kidney and other vascular beds. Removal of the contralateral kidney at the time of ureteral constriction in an additional group of animals resulted in hypertrophy and vasodilation of the obstructed kidney which was not altered by thromboxane or cyclooxygenase inhibition. We conclude that in the neonatal kidney subjected to ipsilateral chronic partial ureteral obstruction, vasoconstriction is mediated at least in part by angiotensin II, but not by thromboxane. Furthermore, vasodilation of the obstructed kidney resulting from contralateral nephrectomy is not dependent on prostaglandin synthesis. Renal vascular resistance of the kidney with prolonged partial ureteral constriction in early development thus appears to be inversely related to renal growth and is not significantly mediated by endogenous prostanoids.

Angiotensin II↗

Acute amoxicillin nephrotoxicity following an overdose.

A 3 year old boy developed acute renal failure following an ingestion of 574 mg/kg of amoxicillin. Accidental ingestions of oral penicillins occur commonly, and are usually considered completely nontoxic. Based on this case, however, the possibility of adverse effects following large oral doses of penicillin-type antibiotics, mediated by allergic hypersensitivity or direct toxicity, should be considered.

Acute Kidney Injury↗

Hemodynamic effects of enalapril on neonatal chronic partial ureteral obstruction.

To evaluate the role of angiotensin II (ANG II) in renal vasoconstriction due to ipsilateral CPUO, guinea pigs were subjected to incomplete left ureteral stenosis within the first 48 hr of life, and were given enalapril from the 14th day of life until study at 23 +/- 3 days or 8 weeks of age. Renal blood flow (RBF) was measured using radioactive microspheres, and glomerular filtration rate (GFR) was derived from inulin extraction. The number of perfused glomeruli per kidney was determined following in vivo India ink perfusion. Enalapril treatment resulted in an 83% rise in RBF of the obstructed kidney, from 2.58 +/- 0.26 to 4.73 +/- 0.48 ml/min (P less than 0.001), which was associated with a 26% increase in number of perfused glomeruli (P less than 0.01). Mean GFR of the hydronephrotic kidney increased from 0.13 +/- 0.02 to 0.37 +/- 0.10 ml/min (P less than 0.05). Enalapril had no effect on intraureteral pressure of the obstructed left kidney after 7 to 13 days of administration, and did not affect renal mass or ureteral diameter after 6 weeks of treatment. It is concluded that hemodynamic consequences of CPUO in the neonate may be attenuated by ANG converting enzyme inhibition. The primary effect of enalapril is most likely inhibition of intrarenal ANG II formation.

Angiotensin II↗

Effects of acute uninephrectomy and age on renal blood flow autoregulation in the rat.

We previously showed that renal autoregulatory behavior is modified by both normal and compensatory renal growth. To determine whether the hemodynamic changes precede an increase in renal mass, the relationship of renal blood flow (RBF) to renal perfusion pressure (RPP) was examined in the remaining kidney of anesthetized young and adult rats 30 min following contralateral nephrectomy. In young control animals 32-41 days old, an autoregulation factor (AF) of 0.37 +/- 0.10 (SE) over RPP 70-100 mmHg indicates efficient autoregulation and did not change during the experiment. Acute uninephrectomy in young hydropenic rats resulted in a 16% increase in RBF at normal RPP, and AF increased to 1.22 +/- 0.34 for RPP 70-100 mmHg, reflecting marked impairment of autoregulation. In young animals in which saline infusion was not reduced at the time of uninephrectomy, RBF increased 22% at normal RPP, and autoregulation was similarly impaired (AF 0.92 +/- 0.12 for RPP 70-100 mmHg). Acute uninephrectomy in adult rats resulted in a 13% increase in RBF, with better preservation of AF (0.48 +/- 0.09) over the adult autoregulatory range (RPP 100-130 mmHg). These findings indicate that profound hemodynamic changes take place in the remaining kidney within 30 min of acute uninephrectomy and that they are qualitatively similar to those observed after compensatory hypertrophy has developed.

Aging↗

Modification of a disposable needle for renal biopsy in children and transplant recipients.

While use of a disposable biopsy needle (Tru-Cut) has been shown to result in less distortion of glomerular architecture than the reusable Franklin-Vim-Silverman needle, the long specimen notch (20 mm) makes it less desirable for use in small children or renal allograft biopsy. A simple modification of the cannula handle permits selection of any desired specimen length. Four percutaneous renal biopsies of nephrotics under 4 years of age and an additional four renal allograft biopsies were performed using this technique, resulting in adequate specimens and no complications. It is concluded that the described modification of the Tru-Cut needle may increase the safety of renal biopsy in patients at higher risk for hemorrhagic complications.

Biopsy, Needle↗

Bladder polyp and heavy proteinuria in a patient with Hodgkin's disease in remission.

A 21-year-old man who developed heavy proteinuria 8 years after remission of Hodgkin's disease treated with MOPP chemotherapy and radiation therapy is reported. Evidence of Hodgkin's disease could not be documented, and minimal changes were revealed by renal biopsy. Proteinuria persisted for 20 months and was followed by dysuria and the discovery of an inflammatory polyp of the bladder. The proteinuria decreased 1 month after excision of the polyp, and disappeared during the following year. Rather than indicating relapse of lymphoma, proteinuria in this patient resulted from a lesion not previously associated with Hodgkin's disease, but possibly resulting from long-term effects of therapy.

Adult↗

Nephrosonography and renal scintigraphy in evaluation of newborn with renomegaly.

Prompt diagnosis of renomegaly in the newborn is necessary for appropriate medical or surgical management to insure maximal recovery of renal function. To investigate both renal structure and function without iodinated contrast infusion, combined ultrasonography and nuclear scintigraphy were evaluated in 17 newborns with renomegaly and 6 infants with cystic renal abnormalities detected in utero. In 18 patients, intravenous pyelography (IVP) and/or voiding cystourethrography (VCUG) were performed subsequently. While ultrasonography or scintigraphy alone provided the major diagnosis in 48 per cent and 30 per cent of cases, respectively, the combination of both studies yielded the major diagnosis in 87 per cent. Subsequent IVP was less informative than combined sonography and scintigraphy in 5 of 15 patients, and VCUG confirmed the final diagnosis in 4 of 13 patients. We conclude that initial evaluation of the newborn with renomegaly should comprise ultrasonography followed by nuclear scintigraphy. This combination of studies provides adequate information to determine subsequent management in nearly 90 per cent of cases without subjecting infants to the risks of contrast infusion or higher doses of diagnostic levels of radiation.

Female↗

Chronic partial ureteral obstruction in the neonatal guinea pig. I. Influence of uninephrectomy on growth and hemodynamics.

Although obstructive nephropathy is a frequent cause of renal insufficiency in infancy, factors influencing adaptation to chronic partial ureteral obstruction (CPUO) are poorly understood. Guinea pigs were subjected to unilateral CPUO within the first 2 days of life (Group I) and microsphere studies were performed at 23 +/- 3 days of age. To also investigate the role of functional renal mass on growth and hemodynamics, contralateral nephrectomy was performed in Group II at the time of ureteral constriction. Compared to sham-operated controls (ureteral diameter = 1 mm) CPUO caused impaired somatic growth in both groups. Resulting hydroureteronephrosis was variable and most severe (ureteral diameter greater than 3 mm) in azotemic animals of Group II, which demonstrated reduced compensatory renal hypertrophy and poorest somatic growth. Mean arterial blood pressure was not affected by CPUO or uninephrectomy. Renal blood flow (RBF) was higher in Group II than Group I, and did not fall significantly with severity of CPUO in Group II, in which number of perfused glomeruli was similar to controls. In contrast, renal vascular resistance (RVR) increased by 172% in animals of Group I with severe CPUO, and was associated with 34% fewer perfused glomeruli than in the hypertrophied contralateral kidney. With increasing severity of CPUO, RBF tended to be distributed to outer cortical regions in the obstructed kidney of Group I, while the shift in RBF distribution was from outer to inner cortex in the remaining kidney of Group II. Filtration fraction fell as a result of CPUO in both groups, such that reduction in the glomerular filtration rate was due in large part to factors other than RBF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗