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S Christensen

Publications and source records attributed to S Christensen.

At least 145 records · Page 8Linked to original sources
PubMed1989

Atubular glomeruli in lithium-induced chronic nephropathy in rats.

Chronic renal failure was induced by administering lithium orally to 14 newborn rats. Seven rats were treated for 8 weeks followed by 8 weeks without lithium (group Li/C) and seven for 16 weeks (group Li/Li). Plasma urea and renal concentrating ability were measured, and one kidney fixed by vascular perfusion. Mean glomerular volume as well as volumes of individual glomeruli were estimated. In addition, the structural integrity between the glomerulus and the proximal tubule was investigated on serial sections. No sclerotic glomeruli were present. Only 37.6 and 27.9% of the glomeruli in the Li/C and Li/Li groups, respectively, were connected to a normal proximal tubule, and most remaining glomeruli were atubular. The mean glomerular volume was unchanged in the Li/C group and reduced by 40% in the Li/Li group. The intraindividual variation in glomerular volume was about 10-fold larger in the lithium-treated groups than in controls. The glomeruli connected to normal proximal tubules had the largest volumes, and hypertrophied glomeruli were encountered more frequently in the Li/C group than in the Li/Li group. There was a significant positive correlation between the plasma urea and the fraction of glomeruli that were not connected to normal proximal tubules. We previously demonstrated in this lithium model that there is a significant correlation between the tubulointerstitial lesion and the impairment of renal function. However, with the demonstration of atubular glomeruli we have a new explanation for the reduction in renal function in this model.

Animals↗
PubMed1988

Lithium-induced structural changes in the cortical distal nephron localized by computer-assisted three-dimensional reconstruction.

Lithium treatment is known to cause tubule dilation in distal nephron segments both in rat and in man. However, due to the heterogeneous cell composition of the distal nephron and the cellular changes following lithium treatment, it has been difficult to identify the structurally changed segments. In this study we have therefore applied computer-assisted reconstruction of cortical distal nephron segments. Tubule dilation was demonstrated in connecting and initial collecting tubules and in the first part of cortical collecting ducts (CCD) whereas it was absent from distal straight and distal convoluted tubules. Principal cells (P cells) in the CCD showed swelling of the cytoplasm, accumulation of actin-like microfilaments, and abnormal arrangements of basolateral membranes. Connecting tubule cells (CNT cells) showed similar but less pronounced changes. Intercalated cells (I cells) showed an accumulation of vesicles in the apical cytoplasm and a reduced luminal surface area. Lesions in P and CNT cells may, at least in part, explain the diabetes insipidus and sodium loss found during lithium treatment. Proton secretion in I cells is probably mediated by an ATPase present in the luminal membrane. The reduction in area of this membrane may explain why lithium-treated animals have a lowered ability to excrete an acid load.

Animals↗
PubMed1988

Atrial content and plasma levels of atrial natriuretic peptides in rats with chronic renal failure.

The possible role of atrial natriuretic peptides (ANP) for the adaptive changes in renal Na excretion during chronic renal failure was studied in 5/6 nephrectomized (NX) rats maintained on a normal (100 mmol/kg) and a high (800 mmol/kg) Na diet. Atrial content of natriuretic substances was determined by bioassay and plasma ANP by radioimmunoassay. Nephrectomized rats showed a twofold increase in plasma ANP irrespective of their Na intake. Atrial ANP content was increased by high Na diet but unchanged by NX. Nephrectomized rats maintained on high Na diet showed partial depletion of atrial ANP stores. There were no significant changes in the volume fraction of atrial granules determined. The results suggest that ANP is involved in the regulation of renal Na excretion during chronic renal failure and acute Na loading; other mechanisms are probably involved in the adaption to chronic Na loading.

Animals↗
PubMed1988

Effects of furosemide on renal haemodynamics and proximal tubular sodium reabsorption in conscious rats.

1. The effects of furosemide given as constant i.v. infusion (7.5 mg kg-1 h-1) or bolus injections (0.5, 7.5 and 120 mg kg-1) on renal haemodynamics and proximal tubular Na reabsorption were studied in conscious water diuretic rats. The clearance of Li (CLi) was used as marker for Na delivery from the proximal tubules, and clearance of [14C]-tetraethylammonium (CTEA) and [3H]-inulin (CIn) as markers for renal plasma flow (RPF) and glomerular filtration rate (GFR), respectively. 2. Furosemide caused a transient increase of RPF and GFR followed by a secondary decrease below baseline levels; the latter could in part be counteracted by volume replacement. The filtration fraction (FF = GFR/RPF) was not significantly changed by furosemide. Fractional proximal Na excretion (CLi/CIn) was significantly increased by all doses of furosemide independent of changes in RPF, GFR and FF. 3. The peak diuretic/natriuretic effect of furosemide was markedly potentiated by volume replacement, probably due to prevention of antinatriuretic mechanisms triggered by volume depletion. 4. It is concluded that following i.v. furosemide administration there is a biphasic change in renal haemodynamics in conscious, restrained rats, and that the inhibition of proximal Na reabsorption, as manifested by changes in fractional Li excretion, is not likely to be due to changes in total renal haemodynamics.

Animals↗
PubMed1988

Lithium-induced morphological changes in the rat kidney at different levels of urine flow.

Lithium treated rats become polyuric and at the same time develop pronounced dilatations of distal tubular segments and characteristics enzyme histochemical changes. In the present study we have compared lithium-polyuric Wistar rats with lithium treated rats in which the polyuria was prevented either by administration of a vasopressin analogue or by water restriction. The kidneys were studied using enzyme histochemistry and light microscope morphometry. The characteristic lithium induced changes were present in all groups irrespective of the presence or absence of polyuria. It is concluded therefore, that the morphological and enzyme histochemical changes are induced by the lithium ion per se and not by the accompanying polyuria.

Animals↗
PubMed1988

Sub-Parts-Per-Billion Nitrate Method: Use of an N(2)O-Producing Denitrifier to Convert NO(3) or NO(3) to N(2)O.

A more sensitive analytical method for NO(3) was developed based on the conversion of NO(3) to N(2)O by a denitrifier that could not reduce N(2)O further. The improved detectability resulted from the high sensitivity of the Ni electron capture gas chromatographic detector for N(2)O and the purification of the nitrogen afforded by the transformation of the N to a gaseous product with a low atmospheric background. The selected denitrifier quantitatively converted NO(3) to N(2)O within 10 min. The optimum measurement range was from 0.5 to 50 ppb (50 mug/liter) of NO(3) N, and the detection limit was 0.2 ppb of N. The values measured by the denitrifier method compared well with those measured by the high-pressure liquid chromatographic UV method above 2 ppb of N, which is the detection limit of the latter method. It should be possible to analyze all types of samples for nitrate, except those with inhibiting substances, by this method. To illustrate the use of the denitrifier method, NO(3) concentrations of <2 ppb of NO(3) N were measured in distilled and deionized purified water samples and in anaerobic lake water samples, but were not detected at the surface of the sediment. The denitrifier method was also used to measure the atom% of N in NO(3). This method avoids the incomplete reduction and contamination of the NO(3) -N by the NH(4) and N(2) pools which can occur by the conventional method of NO(3) analysis. N(2)O-producing denitrifier strains were also used to measure the apparent K(m) values for NO(3) use by these organisms. Analysis of N(2)O production by use of a progress curve yielded K(m) values of 1.7 and 1.8 muM NO(3) for the two denitrifier strains studied.

Journal Article↗
PubMed1988

Early renal changes in lithium-treated normal and vasopressin-deficient rats.

The effects of lithium (Li) on the kidney were studied in normal Long Evans (LE) rats and in rats of the Brattleboro strain (DI rats) which have a congenital (hypothalamic) diabetes insipidus. The rats received a moderate daily oral dose of Li for 4 weeks. The renal cortex of untreated DI rats showed no changes compared with LE rats, but in their medullary collecting ducts (CD) the cells appeared more voluminous, and by light microscope morphometry (outer medulla) their volume fraction was increased. Furthermore, there was an increase in the enzyme histochemical activities of succinate and alpha-glycerophosphate dehydrogenases, most pronounced in the inner medullary zone. Li-treated LE rats and DI rats both showed the same degree of cortical and medullary changes. In the cortex, the light microscope and enzyme histochemical changes were confined to the connecting tubules (CNT) and CD. In the outer and inner medullary zones the increase in CD volume fraction and enzyme activity was much more pronounced than in untreated DI rats. Morphometry of the inner stripe of the outer medullary zone showed the same decrease in the volume fraction of the distal straight tubules (DST) in DI rats with and without Li treatment, as well as in Li-treated LE rats compared with normal LE rats. This decrease may be due to the lack of vasopressin-mediated cyclic AMP generation in the DST of these three groups of animals. It is concluded that the changes induced by Li in the DST are likely to be due to impairment of the vasopressin response known to be present in this segment. However, in the CNT and in the cortical and medullary CD there are changes which are effects of Li not related to the cellular actions of vasopressin.

Animals↗
PubMed1988

Lithium clearance as an indicator of proximal tubular sodium handling during furosemide diuresis.

To evaluate the use of the renal Li clearance as an indicator of proximal tubular Na handling during furosemide diuresis, clearance experiments were performed in conscious catheterized rats. Maximal depression of proximal Na reabsorption was induced by isotonic saline expansion (40 ml/hr) and under these conditions furosemide (7.5 mg/kg/hr) did not increase absolute or fractional clearance of Li. These results provide indirect evidence against the existence of a furosemide-sensitive Li reabsorption in the ascending limb of Henle. The increase of absolute and fractional Li clearance observed in nonexpanded animals given furosemide therefore most likely reflects inhibition of electrolyte reabsorption in the proximal tubules. Using Li clearance as a measure for Na output from the proximal tubules, the study provided information about the contribution of proximal and distal nephron segments to saline expansion natriuresis. The results indicate that the natriuresis is caused by enhanced delivery of Na from the proximal tubules, which is only partially compensated for by a load-dependent increase of absolute distal Na reabsorption, most likely occurring in the thick ascending limb of Henle.

Animals↗
PubMed1987

A morphometric and ultrastructural study of lithium-induced changes in the medullary collecting ducts of the rat kidney.

Rats were given a lithium-containing diet (40 mmol/kg) to study the effect of lithium on the structure of collecting ducts from the inner stripe of the outer medulla. The results show that there is a significant increase in the volume density of collecting ducts already after one week on this diet. The volume density of both intercalated and principal cells increases, whereas the volume density of mitochondria in the cytoplasm increases in the intercalated cells only. The increased volume of both principal and intercalated cells seems to be part of a general hyperplasia and hyperactivity of the collecting duct, which may in some way be related to the effects of lithium on vasopressin-mediated mediated water transport. The specific changes in the intercalated cells may be a consequence of the effects of lithium on distal nephron potassium and hydrogen ion transport in the distal nephron.

Animals↗
PubMed1987

Superiority of tetraethylammonium to p-aminohippurate as a marker for renal plasma flow during furosemide diuresis.

The renal clearances (C) of p-aminohippurate (PAH) and tetraethylammonium (TEA) as markers for renal plasma flow (RPF) were compared in rats under different experimental conditions. CTEA and CPAH were of the same magnitude and varied synchronously during volume expansion and anesthesia. The renal extractions of the two substances were closely correlated and averaged 85.9% for PAH and 88.7% for TEA (p less than 0.01). High doses of furosemide (120 mg/kg as intravenous bolus) reversibly decreased the CPAH/CTEA ratio, suggesting that furosemide may compete for PAH secretion in the proximal tubule. A similar effect was observed after administration of probenecid. The results indicate that TEA is a more reliable indicator of RPF than PAH in studies involving accumulation of endogenous or exogenous organic anions.

Aminohippuric Acids↗
PubMed1987

Effects of selected fee schedule options on physicians' Medicare receipts.

The Congress has indicated interest in modifying the system by which Medicare pays for physicians' services, and implementation of a Medicare fee schedule may be the most feasible change in the near term. In this article, the effects on physicians' Medicare receipts of a variety of fee schedules are simulated using 1984 Medicare claims data for a nationally representative sample of physician practices. The results show that reasonable choices concerning specialty and geographic differentials would shift payments away from surgical specialists and urban areas toward generalists (general practitioners, family practitioners, and internists) and less urban areas.

Data Collection↗
PubMed1987

Acute health care costs for the aged Medicare population: overview and policy options.

Despite its seeming largesse, Medicare has always been a cost-sharing program. The potential costs borne by beneficiaries can be substantial, leading to more than 70 percent seeking protection through supplementary private insurance. Others risk payment out of pocket, and fewer rely on Medicaid. Actual costs incurred by each group of Medicare beneficiaries are examined and seen to have significant and inequitable impacts. Current Medicare policies are often poorly designed or irrelevant. Future responses will have to address both taxation and copayment while weighing concerns for individual financial hardship against possible overuse of services.

Acute Disease↗
PubMed1987

Dose dependence of proximal and distal tubular effects of furosemide in conscious rats.

The dose-response relationship for the diuretic effect of furosemide, given as i.v. bolus injections (0.1-480 mg/kg) was investigated by clearance technique in conscious rats. By measuring the renal Li clearance, the effects on proximal and distal nephron segments were separated, and peak responses were correlated to the maximal excretion rate of furosemide in the urine. At the highest dose of furosemide, fractional Na excretion was increased from 1 to 19%, due to inhibition of fractional proximal Na reabsorption from 65 to 40% and fractional distal Na reabsorption from 97 to 57%. Furosemide inhibition of fractional proximal Na reabsorption showed a maximum at intermediate doses (7.5 mg/kg), whereas there was no maximum for the inhibition of distal fractional Na reabsorption. The natriuretic response was shorter than expected from the decline in furosemide excretion due to an abrupt fall in glomerular filtration rate and a rapid normalization of proximal fractional Na reabsorption. It is suggested that the maintenance of a normal delivery of tubular fluid to the distal nephron during furosemide-induced volume contraction may be due to inhibition of proximal tubular reabsorption.

Animals↗