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Biomedical subjects

H J Gundersen

Publications and source records attributed to H J Gundersen.

At least 91 records · Page 5Linked to original sources

Calcifications, narrowing and rugosities of the leg arteries in diabetic patients.

The large arteries in the leg were examined at angiography in 47 insulin dependent diabetics. Arterial lumen size and the short- and long-range variation as well as intima and linear media calcifications were evaluated quantitatively. Significant correlations were obtained between the duration of diabetes on the one hand and media calcification and uniform narrowing of femoral, crural and foot arteries, as well as increased short-range lumen variation on the other hand. Statistically, the narrowing of the femoral artery and the increased short-range, small-scale variation of its lumen were closely related, whereas media calcifications per se appeared unrelated to the lumen size, locally as well as globally. A high degree of concordance was found among the femoral, crural and foot arteries with respect to both the presence of linear media calcifications and their severity. Spotty intima calcifications were clearly associated with irregular arterial narrowing, but were dependent on age and not on the duration of diabetes. It is suggested that the uniform media calcification, narrowing of the arteries and short-range, small-scale variations of the lumina are expressions of a specific diabetic macroangiopathy.

Adult↗

Diabetic glomerulopathy. Structural characteristics of the early and advanced stages.

Studies of the glomerular structure in diabetes mellitus have helped to elucidate the basis for some functional abnormalities. The decline in glomerular filtration occurring in many long-term diabetics is a functional disorder of great clinical importance. Quantitative structural studies of the glomeruli in diabetics at different stages of disease are necessary to learn about the development of structural changes leading to the end-stage kidney disease. Preliminary results of a study of glomeruli from long-term diabetics with clinical nephropathy are compared with those obtained in control subjects and in diabetics within the first 5 yr of disease. In the long-term diabetics the peripheral basement membrane thickness was doubled. On the average, mesangial regions occupied nearly 60% of the total tuft volume as compared with 33% in the early stages. A marked accumulation of basement membrane material in the mesengial regions had taken place so that 85% of the total basement membrane material of the tufts (i.e., peripheral basement membrane in the capillary walls plus mesangial basement membrane-like material) was localized within the mesangial regions. In the early stages equal amounts were found at these two different sites. The distribution of the lesions within the kidney is under investigation in a light microscopic study of autopsy material from long-term diabetics with varying degrees of glomerulopathy. The severity of the diabetic glomerulopathy was quantitated separately within the superficial and the deep cortical zones. The results showed that there was no tendency toward increased severity in the deep glomeruli.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Estimation of the three-dimensional wall thickness of completed remodeling sites in iliac trabecular bone.

The wall thickness of completed remodeling sites in trabecular bone was estimated in 25 normal individuals and 5 patients with arthrosis of the knee, using 7 micron sections of undecalcified iliac crest bone. A systematic sampling procedure which gives a surface referent estimate of the thickness was applied. The efficiency of the sampling design was optimized by means of a cost-variance analysis. The proposed method of sampling which eliminates a common bias in bone histomorphometry is recommended for determinations of wall thickness, osteoid thickness, lamellar thickness, and distance between fluorochrome markers in trabecular bone. The intraindividual distributions of three-dimensional wall thickness were reconstructed from the measurements of apparent width by an unfolding procedure based on the geometric probability density function pertaining to randomly sectioned plates. Distributions of true wall thickness for the young normal individuals were unimodal and resembled normal distributions. The three-dimensional mean wall thickness was 61.4 +/- 4.4 micron (+/- SD). It was demonstrated that the conventionally applied stereological transformation, which calculates the three-dimensional mean wall thickness from the mean apparent width by multiplying the latter by pi/4, underestimates the three-dimensional mean wall thickness. An improved transformation is illustrated and is recommended for estimating three-dimensional mean thickness of plates from two-dimensional measurements in trabecular bone.

Adult↗

Development of glomerular lesions in experimental long-term diabetes in the rat.

Exact parameters for relevant glomerular structures in the course of streptozotocin diabetes in rats with 1 to 18 months' duration were obtained with stereological methods. Renal cortical tissue from diabetic (D) and control animals (C) was processed for light- and electron microscopy and measurements were performed on systematically sampled glomeruli. The thickness of the basement membrane (BM) increased with age in both groups, but the rate of increase was 50% higher in D: 19 +/- 1.2 nm/month (mean +/- SD) vs. 13 +/- 0.9 nm/month, P = 0.0003. The time course of other structural quantities was characterized by the acute changes constituting the glomerular hypertrophy, earlier shown to develop within the first few days of diabetes. All these changes were confirmed in the present study: In the earliest phase the diabetic rats showed an increased total volume of glomeruli, mesangium, and mesangial BM material, as well as an increased surface of the capillary walls. However, none of these differences between the groups showed progression with increasing duration. Mesangial changes corresponding to those of the glomerulopathy in long-term diabetes were not demonstrable within the experimental period. The streptozotocin diabetic rat, therefore, is not useful as a model of advanced diabetic glomerulopathy. But the BM thickness follows the same predictable time course as in human diabetes insofar as moderately advanced cases are concerned. BM thickness is the parameter of choice when a potential effect of different variables on the development of diabetic glomerulopathy is under study.

Animals↗

Acute renal hypertrophy in experimental diabetes: lack of effect of short-term growth hormone administration.

Normal and diabetic rats were given daily injections of human growth hormone for four days (5 mg per rat per day). Injected rats showed no differences from uninjected controls with respect to kidney weight or renal content of protein, RNA or DNA. Kidney weight increased by 7% after two days of diabetes and by 20% after four days, but growth hormone caused no augmentation of the hypertrophy. It is concluded that growth hormone plays no role in the initiation of diabetic renal hypertrophy.

Animals↗

Optimizing sampling efficiency of stereological studies in biology: or 'do more less well!'.

The aim of the sampling design for stereology is to obtain the maximal amount of quantitative structural information at a given total cost or effort. Principles of such optimal designs are discussed and methods for generating them are illustrated by a biological example. In general, the variation between different individuals--the biological variation--is the major determinant of overall efficiency, whereas the variation between single microscopic features is unimportant. It follows that the expenditure of time and/or money in order to increase the precision of the individual measurements is irrational in almost all studies where the emphasis is on the biological results.

Animals↗

Irreversibility of glomerular basement membrane accumulation despite reversibility of renal hypertrophy with islet transplantation in early experimental diabetes.

A quantitative morphologic study of the glomeruli in rats after 4 wk of streptozotocin-induced diabetes showed a number of glomerular changes, as previously described. Of particular interest was the increase in the total amount of glomerular basement membrane material [from 0.94 +/- 0.13 (SD) mm3 to 1.26 +/- 0.14 mm3 per kidney]. This parameter did not change after 4 wk of normoglycemia following islet cell transplantation (1.19 +/- 0.17 mm3), nor was the total glomerular volume normalized. The contralateral kidney was weighed and used for estimating the total amounts of protein, RNA, and DNA. Four weeks of diabetes expectedly resulted in a 50% increase in kidney weight, and islet cell transplantation diminished this to 15% in excess of normal. The average cell size (protein/DNA ratio) paralleled the kidney size after diabetes and following transplantation. The average amount of RNA per cell (RNA/DNA) increased significantly after induction of diabetes and was totally normalized after transplantation. Kidney protein concentration (mg protein/mg kidney) remained constant throughout the experiment. Considering that a few weeks of diabetes provokes a large increase in basement membrane material, it is especially noteworthy that 1 mo of normoglycemia is quite insufficient to reverse the accumulation.

Animals↗

Quantitative relationship between glomerular foot process width and proteinuria in glomerulonephritis.

The relationship between foot process fusion (retraction) and proteinuria in glomerular diseases has been known for many years, but only a few quantitative studies have been performed. The quantitative morphometrical method used here makes it possible to estimate the distribution of true foot process width from the observed apparent width on electron micrographs. The true foot process width was analyzed in a consecutive material of patients with glomerulonephritis and related to the diurnal urinary protein excretion. Only a weak correlation was found between these two parameters. Albeit an abnormal foot process width was invariably associated with proteinuria, a rather large fraction of patients with gross proteinuria had normal foot process width compared to control subjects. Thus, if foot process fusion causes proteinuria, this can not be the only mechanism leading to this permeability alteration. On the other hand, our results show that foot process fusion is not a necessary consequence of proteinuria. In addition, a methodologic study was performed, analyzing the relationship between the quantitative and a semiquantitative method for estimating foot process fusion. It is concluded that the latter method is fast and sufficiently precise for most evaluations of foot process width in human kidney biopsies.

Biopsy↗

Glomerular epithelial foot processes in normal man and rats. Distribution of true width and its intra- and inter-individual variation.

The width of individual glomerular epithelial foot processes appears very different on electron micrographs. A method for obtainining distributions of the true width of foot processes from that of their apparent width on electron micrographs has been developed based on geometric probability theory pertaining to a specific geometric model. Analyses of foot process width in humans and rats show a remarkable interindividual invariance implying rigid control and therefore great biological significance of foot process width or a derivative thereof. The very low inter-individual variation of the true width, shown in the present paper, makes it possible to demonstrate slight changes in rather small groups of patients or experimental animals.

Adolescent↗

Intravenous insulin decreases urinary albumin excretion in long-term diabetics with nephropathy.

The effect of intravenous injection of insulin on heart rate, plasma noradrenaline and urinary excretion rates of albumin and beta-2-microglobulin was examined in 10 long-term diabetics, 5 of whom had albuminuria. --In patients without albuminuria intravenous injection of insulin resulted in changes similar to but less pronounced than those previously observed in short-term diabetics: albumin excretion, plasma noradrenaline and heart rate increased, creatinine excretion decreased significantly. --Intravenous injection of insulin increased heart rate but not plasma noradrenaline in long-term diabetics with albuminuria. Arterial blood pressure did not change after insulin. Contrary to expectation insulin decreased urinary albumin excretion (from 418 to 312 micrograms/min, 27 per cent) in these patients. There was a marked decrease in urinary excretion rates of beta-2-microglobulin and creatinine (55 and 17 per cent, respectively) after insulin. --The decrease in albumin excretion after insulin in diabetics with albuminuria is most likely due to renal vasoconstriction. The absence of a rise in albumin excretion after insulin may be due to severe morphological changes in glomeruli in these patients.

Adult↗

The acute effect of insulin on heart rate, blood pressure, plasma noradrenaline and urinary albumin excretion. The role of changes in blood glucose.

The effect of intravenous insulin (7-8 U as a bolus injection) on renal haemodynamics and urinary excretion of albumin and beta-2-microglobulin was examined in five recent onset juvenile diabetics. Blood glucose concentration was maintained after insulin at unchanged or slightly increased levels by continuous intravenous glucose infusion (50 g/100 ml, 1.2 ml/min). Mean arterial blood pressure increased slightly but significantly from 94 +/- 8 mmHg to 99 +/- 10 (mean +/- SD) after insulin. The rise in heart rate (16 versus 29 beats/min) and in plasma noradrenaline (from 0.16 to 0.32 ng/ml versus 0.20 to 0.49 ng/ml) was significantly greater in the tilted position after insulin. There was no decrease in glomerular filtration rate or renal plasma flow after insulin, in contrast to the findings after intravenous injection of insulin without maintenance of plasma glucose. Urinary albumin excretion was approximately doubled after insulin, from 6.8 to 12.5 microgram/min. Beta-2-microglobulin excretion decreased but this difference was not significant. -- It is concluded that the rise in heart rate and plasma noradrenaline, and the increase in urinary albumin excretion, after insulin, are unrelated to changes in blood glucose concentration. It is suggested that increased albumin excretion after insulin is due to a direct effect of insulin on glomerular endothelial or epithelial cells.

Adult↗

Fast accumulation of basement membrane material and the rate of morphological changes in acute experimental diabetic glomerular hypertrophy.

Renal glomerular structures have been studied during the initial phases of renal and glomerular hypertrophy in streptozotocin diabetic rats. -- After four days of diabetes significant increases were found in the following absolute structural quantities: the tuft volume (25%), the surface area (42%) and volume (46%) of peripheral basement membrane, and capillary luminal volume (29%). No further changes in these quantities took place over the succeeding 47 days. The geometry of the capillaries, however, changed over this period: at 4 days the total capillary length had increased significantly (32%) with an unchanged average cross sectional area, whereas at 47 days the length had reverted to normal, but average cross sectional area had increased (30%). The increased surface of filtering area may be the morphological counterpart of increased glomerular filtraton rate. The changes in glomerular volume were thus accompanied by changes in glomerular structural composition which after a few weeks returned to normal, in balance with the increased volume.

Aging↗

Renal hypertrophy in experimental diabetes. A morphometric study.

Renal hypertrophy in rats with streptozotocin diabetes or after unilateal nephrectomy was studied by sterological techniques. -- After 4 days of diabetes total glomerular volume had increased by 30%, and after 47 days by 43%. Glomerular growth was more pronounced than whole kidney growth during the first 4 days, but subsequently whole kidney growth exceeded glomerular growth. In control rats glomerular volume was 4.9% of total kidney volume; after 4 days of diabetes it was 5.4% and after 47 days 4.1%. -- Proximal tubule length increased from 366 m/kidney in control rats to 447 m/kidney after 47 days of diabetes; tubular luminal diameter increased from 26.8 micrometer to 31.4 micrometer in the same rats. Tubular length and luminal diameter were, however, not increased after 4 days of diabetes. -- In unilaterally nephrectomised rats there was no early rapid glomerular growth. Glomerular fractional volume was 4.9% in controls, 4.4% at four days, and 4.2% at 24 days after nephrectomy. -- The results indicate a disturbed glomerulo-tubular balance in the early phases of diabetic renal hypertrophy.

Animals↗