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Biomedical subjects

B H Brouhard

Publications and source records attributed to B H Brouhard.

At least 73 records · Page 4Linked to original sources

Short-term protein loading in diabetics with a ten-year duration of disease.

The concept of renal functional reserve has recently been introduced. To test this ability of the kidneys to increase the glomerular filtration rate (GFR) above the baseline level, the GFR response to short-term protein load was measured. Recent studies have provided conflicting data concerning the GFR response to a protein load in insulin-dependent diabetics who are known to have increased baseline GFRs. Thus, we studied nine insulin-dependent diabetics with a disease of at least a ten-year duration (none were hypertensive or proteinuric) and compared their data with those of five nondiabetic controls with normal renal function. All the diabetics, except one, showed a significant increase in GFR (mean +/- SEM, 60 +/- 9 to 74 +/- 14 mL/min/sq m); the controls also had increased GFRs (mean +/- SEM, 53 +/- 6 to 69 +/- 6 mL/min/sq m). The one patient who demonstrated no rise in the GFR had the lowest GFR measured, 33 mL/min/sq m. To explore the mechanism of this response, we measured the plasma levels of putative mediators glucagon and human growth hormone. Although glucagon showed the expected rise after the protein meal, the variability was so large that no statistically significant relationship could be identified. Human growth hormone remained constant and low in the controls and showed more variability and was higher in the diabetics; again, no relationship to the GFR could be demonstrated. Thus, our data demonstrated a normal response to a short-term protein load by a group of well-defined diabetic subjects who would be at risk to show subtle renal abnormalities.

Adolescent↗

The role of dietary protein in progressive renal disease.

Recently, a renewed interest in the role of dietary protein intake in the treatment of progressive renal disease has occurred. Early investigators suggested that high protein intake had a deleterious effect on renal function. Animals fed a high protein intake had more proteinuria and more-extensive glomerular sclerosis compared with animals fed a normal protein intake. More recent investigations have revealed that not only will a high protein intake exacerbate renal disease but a low protein intake will slow and/or prevent decline in renal function and the severity of renal histologic changes. These studies have provided the stimulus for investigations involving humans. Such studies suggest that patients with progressive renal disease of various causes, when placed on low-protein diets (0.6 g/kg/d), exhibit a slowing of the decline in renal function. The mechanism of the halting of such progression has been suggested to be a reduction in the hyperfiltration that occurs in the remaining nephrons after renal injury is established. Micropuncture studies have indicated that after the kidney has suffered injury, either through disease process or surgical removal, the unaffected nephrons try to maintain overall function, with individual nephrons increasing their filtration. This increase in single-nephron glomerular filtration rate (GFR) is accompanied by increases in single-nephron blood flow and an increase in transcapillary pressure, with altered membrane permeability, resulting in increased proteinuria. This increase in filtered albumin is taken up by the mesangium, with resulting mesangial expansion and glomerular sclerosis, with impingement on the glomerular filtering surface area, ultimately resulting in further decreases in GFR. Lowering protein intake will prevent this hyperfiltration, albuminuria, and the histologic changes. Furthermore, whether reduced protein intake is needed during times of physiologic increases in GFR (pregnancy, unilateral nephrectomy) is not clear. The processes that occur from the time after ingestion of protein to changes in GFR are not known but are probably mediated by systemic or intrarenal hormones. When adjusting protein intake, the minimum recommended dietary allowance for daily protein requirements must be considered. In adults, this level is 0.5 g/kg/d, with lower intakes requiring supplementation with essential amino acids. Requirements for children vary according to age--the younger the child, the higher the requirement. Minimum requirements for children with renal insufficiency have not been established.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Percutaneous renal biopsy in infants and young children.

Records of 55 percutaneous renal biopsies performed in 53 children aged 5 days to two years were reviewed. Radiographic or ultrasound imaging techniques were not utilized during the biopsy procedure. Forty-nine of 55 biopsy attempts yielded sufficient tissue for histologic evaluation (89.1%). Transient gross hematuria not requiring intervention was the sole complication and was noted in 6 of 55 biopsy attempts (10.9%). Percutaneous renal biopsy can be performed safely in very young children and the success of the procedure is comparable to that in older children.

Age Factors↗

Concentrations of prostaglandins in plasma, seminal vesicles, and ovaries of aging C57BL/6NNia mice.

Concentrations of prostaglandin E1 (PGE1), and prostaglandin E2 (PGE2) (combined in the same radioimmunoassay) and prostaglandin F2 alpha (PGF2 alpha) were analyzed in circulating plasma and seminal vesicles of 3- and 26 to 27-month-old males and in circulating plasma and ovaries of 3-, 6-, 14 to 18- and 26 to 30-month-old female C57BL/6NNia mice. The amount of PGE declined in the plasma (P less than 0.05) and seminal vesicles (P less than 0.02) of aged male mice, whereas PGF2 alpha concentrations remained unchanged. There were no statistical differences in plasma or ovarian concentrations of PGE or PGF2 alpha when comparing the various age groups of female mice. It does not appear as if age-related changes in prostaglandins play a significant role in reproductive senescence.

Aging↗

Acute response of urinary N-acetyl-beta-D-glucosaminidase to mannitol infusion in the dog.

Urinary activity of N-acetyl-beta-D-glucosaminidase (NAG) has been used as an indicator of subtle renal injury in a variety of conditions. Such enzyme activity has been shown to be increased in human and other animals with diabetes mellitus. The mechanism of this increase in urinary NAG activity is not known. To determine if the osmotic diuretic effect of the glycosuria could stimulate urinary NAG activity, mannitol was infused into the left renal artery of six dogs to cause a unilateral osmotic diuresis and compared to the right side. During three control periods of 20 minutes, each urinary NAG excretion (expressed in units as the ratio of NAG activity to urinary creatinine, NAG/Cr) was equal from both left and right kidneys, 5.0 +/- 1.5 vs 6.0 +/- 3.6 units, respectively. During the 11 mannitol infusion periods urine volume and sodium excretion rose significantly from the left kidney, .50 +/- 2 to 1.5 +/- .3 ml/min and 21 + 5 to 99 +/- 16 u Eq/min, respectively. However urinary NAG/Cr did not change, 5.0 +/- 1.5 to 5.1 +/- 1.0 units. In six control dogs not infused with mannitol, urinary NAG/Cr tended to rise with time from control to experimental collection periods, 4.7 +/- 2.0 to 8.1 +/- 3.0 respectively; however these are not significantly different. In all dogs urine volume and sodium excretion tended to rise throughout the course of the study due to hydration with normal saline; thus it is possible that the tendency for urinary NAG activity to rise may have been due to the increase in sodium excretion. However, these studies demonstrate that the osmotic diuresis induced by mannitol produced no significant change in urinary NAG activity. Thus it may be that the hyperglycemia itself, and not the glycosuria, produces the increase in urinary NAG activity seen in the diabetic.

Acetylglucosaminidase↗

Differential response of urinary N-acetyl-beta-D-glucosaminidase to two osmotic diuretics in the dog.

Urinary N-acetyl-beta-D-glucosaminidase (NAG), a lysosomal hydrolase located the proximal tubule of the kidney, has been used as a marker for subtle renal injury. In humans and other animals with diabetes mellitus, urinary NAG activity has been shown to increase within 12 hours of the onset of hyperglycemia and glycosuria. Whether the rise in urinary NAG activity is in response to the hyperglycemia or to the osmotic diuresis associated with glycosuria is not known, nor has the time course of the rise in enzyme activity been determined. A study was designed using four groups of dogs to examine these possibilities: group 1 (n = 5), control dogs; group 2 (n = 5), mannitol-infused dogs; group 3 (n = 5), low-glucose dogs; and group 4 (n = 5), high-glucose dogs. In groups 2 and 4, mannitol and glucose, respectively, were infused at a rate to double urine flow from the left ureter without altering the contralateral urine volume. In group 3, sufficient glucose was infused to elevate left renal vein glucose level without producing glycosuria. In the control dogs infused with normal saline solution at a constant rate throughout the control and study periods, no differences were found in urinary NAG excretion when data from individual clearance periods were compared for the right and left kidneys. In the low-glucose dogs, urinary NAG/creatinine ratios were significantly increased (P less than 0.01) when the left and right kidneys were compared for the duration of the infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗

Response of urinary N-acetyl-beta-D-glucosaminidase to rapid decreases in blood glucose.

Urinary N-acetyl-beta-D-glucosaminidase (NAG) has been shown to be a sensitive indicator of blood sugar control. Twelve insulin-dependent diabetics whose blood glucoses were being controlled with the artificial pancreas had concurrent urinary NAG activity measured. Blood glucose dropped markedly from 198 +/- 22 mg/dl (x +/- SEM) to 121 +/- 7 mg/dl during the 25 h on the artificial pancreas. For the entire group UNAG: UCr dropped from 14.9 +/- 4.4 to 7.25 +/- 1.68 units. In order to determine if larger decreases in blood glucoses over the course of the study resulted in larger decreases in UNAG: UCr, an arbitrary division at 180 mg/dl was made. Six patients with blood glucoses at or above this level at the start of the study showed a drop in both blood glucoses and UNAG: UCr (261 +/- 24 to 134 +/- 12 mg/dl and 21.1 +/- 6.1 to 7.29 +/- 1.53 U, respectively). Even though the other six patients had blood glucoses below the renal threshold, both blood glucoses and UNAG: UCr declined (136 +/- 4 to 110 +/- 4 mg/dl; 8.89 +/- 2.4 to 6.2 +/- 1.64 U, respectively). Thus not only may urinary NAG activity reflect long-term control and renal complications of diabetes, but this enzyme is also responsive to acute changes in blood glucose.

Acetylglucosaminidase↗

Urinary N-acetyl-beta-D-glucosaminidase in streptozotocin-induced diabetic rats.

Excretion of urinary N-acetyl-beta-D-glucosaminidase has been found to be elevated in diabetic humans and rats. This urinary glycosidase may reflect blood sugar control over time, since it has been significantly and positively correlated with hemoglobin A1 in children with insulin-dependent diabetes. Other studies have suggested that urinary NAG may predict diabetic nephropathy. In order to more carefully define the relationship between urinary NAG excretion and blood and urine sugars, hemoglobin A1, and microalbuminuria, 48 rats were made diabetic by the use of streptozotocin. All rats were uninephrectomized at 3 weeks. Of these, 23 were treated with daily insulin injections, 25 were untreated, and both groups were compared to 13 control, nondiabetic rats. Urine volume, glucose, albumin, and blood sugar were all significantly (P less than 0.05) elevated in the untreated rats compared to the treated and control groups. Urinary NAG:UCr was significantly (P less than 0.01) elevated in the untreated group with lower but still elevated levels (P less than 0.05) in the treated rats. To further define the time course of the increase in UNAG:UCr 12 rats were followed serially at 12-hr intervals for 92 hr after streptozotocin. Urinary NAG increased significantly (P less than 0.05) at 12 hr after streptozotocin injection and reached a plateau at 36 hr while hemoglobin A1 did not rise until 2 weeks after onset of hyperglycemia. Urinary NAG increases more rapidly than hemoglobin A1 after onset of hyperglycemia and glycosuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗

Renal function in children undergoing cardiac operations.

Because we sometimes observed large amounts of uric acid crystals in the urine of infants and children after open-heart operations and since renal insufficiency from any cause can be a serious complication of cardiac procedures, 8 acyanotic and 5 cyanotic children were studied prospectively by comparing several preoperative and postoperative measures of renal function. There were no significant differences between the acyanotic and cyanotic groups in terms of age, time on cardiopulmonary bypass, or other preoperative variables. Postoperatively, children in both groups had a wide range of free water clearances (CH2O), with some values in the range reported to be diagnostic of renal insufficiency in adults. Since none of these children had renal insufficiency by other criteria, CH2O may not be as reliable an indicator of renal insufficiency in children. The major difference between the cyanotic and acyanotic groups was seen in postoperative serum uric acid levels (SUA); the mean SUA levels in the acyanotic and cyanotic groups were 5.3 +/- 0.5 mg/dl (+/- standard error of the mean) and 10.4 +/- 1.7 mg/dl (range, 8.0 to 15.5 mg/dl), respectively. Since the hyperuricemia in the cyanotic children could not be related to increased exogenous administration or decreased renal excretion, it is probably caused by increased endogenous production and may be related to the resolution of the cyanotic state.

Acute Kidney Injury↗

Sodium reabsorption during intrarenal diazoxide infusion in the dog.

Infusion of diazoxide, a potent benzothiazide antihypertensive, into the renal artery results in diuresis and natriuresis. The site within the nephron of decreased reabsorption has been controversial. Thus free flow recollection micropuncture studies of the superficial proximal tubule of the dog were undertaken to determine if diazoxide decreased sodium reabsorption from this part of the nephron. Renal blood flow, monitored by an electromagnetic flow meter, was increased by about 15% with the diazoxide infusion. Systemic blood pressure and hematocrit remained unchanged. Glomerular filtration rate increased significantly from 26 +/- 2 to 34 +/- 3 ml/min, urine flow and sodium excretion also increased (0.13 +/- 0.01 to 0.33 +/- 0.06 ml/min and 5.5 +/- 0.90 to 35.5 +/- 11.0 microEq/min, respectively). Decreased sodium reabsorption from the proximal tubule was demonstrated by a decrease in the tubular fluid to plasma inulin ratio (1.62 +/- 0.1 1.47 +/- 0.1) thus giving a reduction in fractional sodium reabsorption to the site of micropuncture (36.1 +/- 4.3 to 29.5 +/- 5.1%, p less than 0.05). To examine peritubular effects of diazoxide infusion, capillary protein concentration and pressure were measured; the former increasing significantly (9.17 +/- 0.32 to 9.80 +/- 0.35, p less than 0.05) and the latter did not change (13.1 +/- 1.0 vs. 15.2 +/- 1.4 mm Hg). Thus intrarenal diazoxide causes whole kidney vasodilatation with diuresis, natriuresis and decreased sodium reabsorption from the superficial proximal tubule. Additional studies provided no data to indicate that changes in peritubular physical factors account for the changes in sodium handling.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Effective use of captopril in postoperative paradoxical hypertension of coarctation of the aorta.

Severe systemic hypertension may complicate the postoperative course of patients undergoing surgical repair for coarctation of the aorta. The sympathetic and the renin-angiotensin systems have been demonstrated as underlying mechanisms for this paradoxical phenomenon (Farrell et al., 1979; Rocchini et al., 1979). We recently utilized captopril, a competitive inhibitor of angiotensin converting enzyme, with success in the management of severe hypertension that developed in a 15-year-old male after successful surgical repair for coarctation of the aorta. To our knowledge, this is the first report on the use of captopril for the treatment of this paradoxical phenomenon.

Adolescent↗