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N Marcussen

Publications and source records attributed to N Marcussen.

At least 37 records · Page 2Linked to original sources
PubMed1997

Effects of perindopril and hydrochlorothiazide on the long-term progression of lithium-induced chronic renal failure in rats.

Administration of lithium in the diet to new-born rats induces chronic renal failure associated with hypertension, proteinuria and irreversible tubulo-interstitial morphological changes. In the present study we induced chronic renal failure by administration of lithium for 16 weeks to new-born rats, and examined the spontaneous course of this nephropathy and the effects of antihypertensive treatment with either perindopril (12 mg/kg diet) or hydrochlorothiazide (500-1000 mg/kg diet) during a 24 weeks follow up period without lithium. In the placebo group, progression to terminal uraemia occurred in all rats with severe renal failure (initial Purea > 15 mM) (10 of 18). Rats with mild-moderate renal failure (Purea 9-15 mM) showed no deterioration in renal function despite persistent systolic hypertension and irreversible structural renal changes. Perindopril normalized the blood pressure in all rats but did not prevent the progression to terminal uraemia (8 to 18). Hydrochlorothiazide partially controlled the hypertension and accellerated the progression of uraemia without increasing the mortality (7 of 17). Irrespective of treatments, the predominant quantitative structural changes (e.g. decreased volume of proximal tubular cells) showed significant correlations with the degree of renal dysfunction, but not with systolic blood pressure in the surviving rats. It is concluded that progression of lithium-induced nephropathy to terminal uraemia occurs when the nephrotoxic insult results in a more than 50% reduction of the glomerular filtration rate, judged from Purea levels. The failure of effective antihypertensive treatment with an angiotension-converting enzyme inhibitor to modify the progression suggests that in this model, systemic or glomerular hypertension may not be an important pathophysiological factor. The structural and functional deterioration observed in Li-uraemic rats during treatment with hydrochlorothiazide remains unexplained.

Animals↗
PubMed1997

Functional and structural changes in the thick ascending limb of Henle's loop in rats with liver cirrhosis.

Five weeks after common bile duct ligation (CBL), Wistar rats had histologically verified liver cirrhosis with sodium retention but without ascites. Plasma concentrations of vasopressin and aldosterone were normal. Glomerular filtration rate was unchanged, although renal plasma flow was increased. A test dose of furosemide (7.5 mg/kg body wt iv) produced significantly greater diuretic (+59%) and natriuretic (+66%) responses in Wistar CBL rats than in sham-operated controls. Stereological examination of kidneys demonstrated a 47% increase in the volume of the inner stripe of the outer medulla, with a 55% increase in the volume of thick ascending limb of Henle's loop (TALH) epithelium in cirrhotic Wistar rats relative to controls. CBL produced a similar degree of liver cirrhosis in vasopressin-deficient Brattleboro rats. However, both functional and structural renal changes observed in cirrhotic Wistar rats were absent in vasopressin-deficient cirrhotic Brattleboro rats. These results suggest a permissive action of vasopressin for the adaptive changes in TALH in rats with experimental liver cirrhosis. Our results are consistent with the hypothesis that increased sodium chloride reabsorption in the TALH may contribute to the early sodium retention that precedes ascites formation in rats with secondary biliary liver cirrhosis.

Animals↗
PubMed1997

Effects of renal papillary-medullary lesion on the antihypertensive effect of furosemide and development of salt-sensitive hypertension in Dahl-S rats.

To test the hypothesis that the long-term antihypertensive action of furosemide is mediated by a renomedullary vasodepressor substance, we measured mean arterial pressure (MAP) by radiotelemetry in Dahl-S rats with either intact or bromoethylamine-induced (BEA, 100 mg/kg i.p.) lesion of the renal papilla and medulla. Seven days of recovery after BEA administration, the rats diet was changed from 1 to 4% NaCl, and during days 8 to 31, rats were randomized to daily treatment with placebo or furosemide (50 mg/kg p.o.). Then furosemide treatment was stopped and the rat food was changed to 1% NaCl diet. After a 10-day wash-out period, renal function was measured. BEA produced a rapid (within min) and sustained increase in MAP which was accelerated during 4% NaCl diet. Furosemide prevented 4% NaCl-induced hypertension in both rats with intact kidneys and in rats with BEA-induced renal papillary-medullary lesion. A significant decrease in renal plasma flow (-34%) and glomerular filtration rate (-40%) was observed in all BEA-treated rats independent of previous furosemide treatment. In response to an i.v. load of isotonic saline (10% body weight), rats with renal papillary-medullary lesion had an impaired ability to excrete sodium. Histological examination showed that BEA-treated rats had severe lesions of the renal papilla and medulla, with light-to-moderate changes in the renal cortex. It is concluded that the antihypertensive effect of furosemide is not mediated by a renomedullary vasodepressor substance. The accelerated NaCI-sensitive hypertension in rats with BEA-induced renal papillary-medullary lesion is related to an impaired ability to excrete excess NaCl.

Animals↗
PubMed1997

Renal biopsy findings in long-term cyclosporin treatment of psoriasis.

Renal biopsies were performed in 30 psoriatics during long-term low-dose cyclosporin (CsA) therapy (range 2.5-6 mg/kg per day) of from 6 months to 8 years. The study included pretreatment biopsies in 25 of the patients. After 2 years all biopsies shared features consistent with CsA nephropathy despite completely normal pretreatment morphology in 17 of the 25 patients. The severity of the findings which consisted of arteriolar hyalinosis, focal interstitial fibrosis and sclerotic glomeruli increased with length of therapy. Mild renal lesions were seen during the first 2 years. After 4 years all but one had arteriolar hyalinosis, with interstitial fibrosis pronounced in five and moderate in six of 11 patients. At the same time glomerular sclerosis had become significant. A decrease in glomerular filtration rate (GFR) correlated with severity of structural lesions. The data from our study together with experiences from cardiac-transplanted patients treated with CsA indicate that patients with psoriasis after 2 years therapy with CsA should be rotated to other treatments or be followed carefully by GFR and sequential renal biopsies.

Adult↗
PubMed1995

Reproducibility of the Banff classification of renal allograft pathology. Inter- and intraobserver variation.

The present study was undertaken to investigate the inter- and intraobserver variation in use of the scoring system for glomerulitis, vasculitis, interstitial inflammation, tubulitis and arteriolar hyalinosis that is an essential part of the recently proposed Banff classification of renal allograft biopsies. Seventy-seven biopsies done less than 90 days after transplantation were included. The scoring was done blindly by five pathologists on biopsies stained with H&E and PAS. The volume fraction of interstitial inflammation was estimated. Spearman rank correlation coefficient and kappa values were used for the evaluation of reproducibility. The results of both inter- and intraobserver variability showed a good correlation and reasonable kappa values for vasculitis, interstitial inflammatory infiltration, and tubulitis. Less-good correlation was found for glomerulitis and arteriolar hyalinosis. The interobserver kappa score for grading of the rejection severity was 0.40 overall but 0.56 when only presence or absence of acute rejection was considered and 0.66 for presence or absence of vasculitis. Weighted kappa values for interobserver vasculitis score and rejection grading were 0.58 and 0.55, respectively. A strong association existed between the volume fraction of interstitial inflammation and the semiquantitative scoring for interstitial inflammation. In conclusion, the good correlations for the key elements in the grading of the allograft biopsies in the present classification system, confirmed the utility of the defined criteria for grading rejection. More precisely defined criteria or simplification of the scoring system are needed for glomerulitis and arteriolar hyalinosis--parameters not used in the diagnosis of rejection.

Biopsy↗
PubMed1995

Endocapillary glomerulitis in the renal allograft.

Endocapillary glomerulitis is characterized by an increase in number of mononuclear cells in the glomerular capillary lumina. This lesion has been described in the early posttransplant period, but its pathogenesis, relation to conventional rejection, and prognostic impact is not well known. Using the definitions, scorings, and gradings of the Banff system for classification and grading of histopathologic changes in the renal allograft, we have analyzed 444 consecutive renal allograft biopsies from the first 90 days posttransplant. Moderate or severe glomerulitis occurred in 13.5% of the biopsies. There was a strong tendency toward clustering of glomerulitis: if one biopsy from a patient had glomerulitis, there was a high probability that it occurred in other biopsies from the same patient. There was some correlation with conventional acute rejection, but 40% of all biopsies with glomerulitis had no rejection and 53% of all biopsies with rejection had no glomerulitis. Graft function at biopsy was nil or decreased in many patients, but this could largely be explained by the independent presence of primary graft dysfunction or conventional rejection, these conditions being a frequent indication for performing a graft biopsy. Moderate or even severe glomerulitis was, however, compatible with a functioning graft. No correlation between glomerulitis and active CMV infection was found. The one-year graft survival of grafts with early posttransplant glomerulitis was 66%. If early conventional acute rejection is taken into consideration, graft survival does not seem to be influenced by the presence of glomerulitis. Early posttransplant endocapillary glomerulitis may be a peculiar pattern of rejection with a pathogenesis different from that of conventional rejection, but the present investigation does not demonstrate any adverse effects on graft function or graft prognosis.

Adolescent↗
PubMed1995

Atubular glomeruli in chronic renal disease.

The pathological changes in chronic renal failure are heterogeneous and may depend on the primary disease process. Renal function is better correlated with tubular and interstitial changes than with glomerular changes detectable in simple two-dimensional sections. Atubular glomeruli have been demonstrated in many tubulointerstitial disorders. They constitute a significant portion of the glomerular population in some chronic renal diseases. The atubular glomeruli are generally small, but they have open capillaries and minor ultrastructural changes. The number of capillaries is decreased. Glomeruli connected to normal proximal tubules have volumes at the normal level or above. They have not been shown to be eliminated. The presence of atubular glomeruli may explain the correlation between the volume of proximal tubules and the volume of interstitium, on the one hand, and altered renal function on the other. The presence of atubular glomeruli could explain the irreversibility of chronic renal diseases. It is likely that interstitial fibrosis and tubular atrophy in themselves contribute to the decrease in renal function of both glomerular and nonglomerular renal diseases. In glomerular diseases, the glomerular lesion and hyperfiltration may play the major part in the pathogenesis of the deterioration of renal function. The available evidence points toward glomerulo-tubular disconnection as an important and common cause of progression and irreversibility of chronic renal diseases. It provides a simple explanation for the common observation of severely reduced kidney function and mostly normal-looking glomeruli--at least in two dimensions.

Capillaries↗
PubMed1995

Tubulitis in primary vascular and glomerular renal disease.

A semiquantitative light microscopic study of 274 renal biopsy and 12 nephrectomy specimens was carried out to assess the frequency and severity of tubulitis (mononuclear leukocytes in the renal tubular wall) in all common glomerular diseases, diabetic nephropathy, renal amyloidosis and renal artery stenosis. The extent of interstitial inflammatory infiltrates and severity of interstitial fibrosis were also graded. Tubulitis was 1) frequent in crescentic glomerulonephritis (GN) with pauci-immune, linear and granular immune deposits, renal artery stenosis, diabetic nephropathy, lupus GN of WHO type IV, and IgA GN; 2) rare in minimal change and idiopathic membranous nephropathy; 3) usually severe in crescentic GN and renal artery stenosis; and 4) predominantly located in atrophic tubules in renal artery stenosis, diabetic nephropathy and IgA GN. The most important parameter for the grading of tubulitis was interstitial infiltration. However, no correlation was found between the grades of tubulitis, interstitial infiltrates and interstitial fibrosis in crescentic and lupus GN. It is suggested that renal ischemic injury, by eliciting expression of proinflammatory cytokines and neo-antigens in the tubulointerstitial space, might play a role in the development of tubulitis in vascular and glomerular renal diseases.

Diabetic Nephropathies↗
PubMed1995

Cytodiagnostic urinalysis is very useful in the differential diagnosis of acute renal failure and can predict the severity.

Cytodiagnostic urinalysis was tested to determine its utility in the differential diagnosis of acute renal failure (ARF). Fifty-one patients with acute renal failure were included and evaluated clinically with regard to the etiology of the renal failure, whether underlying chronic renal failure was present, and if dialysis was required. Urine specimens were macroscopically examined and subjected to a multiparameter reagent-strip analysis. Papanicolaou stain was done on cytocentrifuge preparations and the number of blood cells, renal cells, and casts examined in a standardized fashion. The results showed that the 34 patients with acute tubular necrosis (ATN) of either ischemic or toxic origin had a higher number of collecting duct cells, and a higher total number of casts than the 17 non-ATN patients. Twelve patients requiring dialysis had a higher number of different types of casts (granular, waxy, leukocytic, broad casts) as well as more renal cells (mainly necrotic) than the 39 patients who did not require dialysis. A significant positive correlation was found between the magnitude of rise of serum creatinine and a number of cytodiagnostic parameters. We conclude that cytodiagnostic urinalysis may be valuable in addition to other tests in the evaluation of patients with acute renal failure.

Acute Kidney Injury↗
PubMed1995

Reproducibility of the WHO classification of glomerulonephritis.

The inter-observer variation of the WHO classification of glomerulonephritis (GN) was studied using Kappa statistics. One hundred renal biopsies were selected with almost equal representation of the following types of GN: minimal change nephropathy, membranous GN, focal proliferative GN, diffuse mesangial proliferative GN, endocapillary GN, membranoproliferative GN, and crescentic GN. Slides stained with silver-methenamine and PAS-hematoxylin were circulated among the members of the panel, who made their diagnoses without knowing those of the other participants and without knowledge of the clinical conditions. There was a very good overall diagnostic agreement of 0.67 with a Kappa value of 0.61, figures which compete very well with other diagnostic systems analysed with Kappa statistics. Analysing the single types of GN, we found that the highest Kappa values were obtained for crescentic GN (0.81), endocapillary GN (0.79) and membranous GN (0.74) and the lowest Kappa values for membranoproliferative GN (0.40) and diffuse mesangial proliferative GN (0.44). Basically, the international classification of GN is founded upon light microscopy. Our results demonstrate that this system works generally well. The diagnostic reproducibility of the types with less satisfactory Kappa values can be expected to be improved by including immunopathology and electron microscopy.

Biopsy↗
PubMed1995

Urethral condylomata, due to human papilloma virus (HPV) type 6/11., associated with transitional cell tumors in the bladder and ureter. A case report.

Condylomata in the urethra usually occur as a complication to genital warts on the external genitals and are most often situated in the distal part of the urethra. This is a report of a male patient with recurring papillomatous transitional cell tumors, stage Ta and T1, grade 2 and 3 in the bladder and the right ureter, who presented with extensive condylomatosis in the urethra from the meatus to the verumontanum, without simultaneous presence of condylomata at the external genitals. Condylomatous fragments were also present in the TUR specimen from the bladder, but may have been displaced from the urethra during cystoscopy. Using PCR technique and in situ hybridisation, HPV types 6/11 were detected in the condylomata, but no virus was present in the transitional cell tumors.

Adult↗
PubMed1994

Compensatory growth of glomeruli is accomplished by an increased number of glomerular capillaries.

BACKGROUND: The number of glomerular capillaries were unbiasedly estimated in the very heterogeneous population of glomeruli found in rats with lithium-induced nephropathy. The glomeruli are atubular, connected to atrophic tubules, or connected to normal proximal tubules. In rats with lithium nephropathy, hypertrophy is found in glomeruli with normal tubular connection. This hypertrophy may take place by an increase in the number, length, or diameter of the capillaries. EXPERIMENTAL DESIGN: In serial sections, the glomeruli were sampled at random and followed to detect whether they were connected to an atrophic tubule, a normal proximal tubule, or no tubule at all. On 1-micron-thick serial sections, the number of capillaries was estimated using a method based on a topologic definition of the capillary. The number was estimated for three categories of glomeruli: normal glomeruli from control animals, hypertrophic glomeruli connected to normal proximal tubules from lithium-treated animals, and atrophic glomeruli being either atubular or connected to atrophic tubules from lithium-treated animals. On the same sections, stereologic methods were used to estimate the cross-sectional area and the length density of the glomerular capillaries. RESULTS: The mean number of capillaries in normal, hypertrophic, and atrophic glomeruli was 188 +/- 26 (+/- SD), 271 +/- 32 (+44%), and 65 +/- 12 (-65%), respectively. Whereas the total length of the capillaries per glomerulus was increased in hypertrophic glomeruli and decreased in atrophic glomeruli compared to normal glomeruli, the mean capillary length of 48.3 +/- 3.7 microns, and 53.0 +/- 11.3 microns in the hypertrophic and atrophic glomeruli, respectively, was significantly higher than the 41.0 +/- 4.6 microns in the controls. CONCLUSIONS: We conclude that in lithium-induced nephropathy, glomerular hypertrophy is mainly due to the increased numbers of capillaries, whereas the increase in the individual capillary length is of lesser importance.

Aging↗
PubMed1993

Morphology of ischemic acute renal failure, normal function, and cyclosporine toxicity in cyclosporine-treated renal allograft recipients.

To characterize morphologic changes in the early post-transplant period in cyclosporine-treated renal allograft recipients, we examined biopsies from three groups of cyclosporine-treated patients: normal function (N = 9), ischemic acute renal failure or "acute tubular necrosis" (N = 12), and cyclosporine toxicity (N = 7). Groups were compared with each other and with previously studied groups of azathioprine-treated patients and native kidney patients. The interstitial infiltrate commonly observed in normally functioning azathioprine-treated grafts was not observed in normally functioning cyclosporine-treated grafts, but two of nine such grafts had a significant venulitis, a change also seen in three of the patients with cyclosporine nephrotoxicity. "Acute tubular necrosis" (ATN) in cyclosporine-treated graft recipients was characterized by focal necrosis of complete tubular cross sections, a finding normally rare in other types of ATN, and by shedding into the tubular lumen of tubular cells with non-pyknotic nuclei, a finding supporting our previous observation of detachment of viable tubular cells in ATN but not in the normal kidney. Hyaline arteriolar thickening was the only morphologic finding on biopsy which distinguished patients with cyclosporine nephrotoxicity from other groups. In summary, the morphologic changes observed in cyclosporine-treated renal allograft recipients with ATN or normal function are quite different from those observed in azathioprine-treated patients. Cyclosporine appears to enhance the tubular injury observed in ATN. Hyaline arteriolar thickening is the main distinguishing feature of cyclosporine nephrotoxicity.

Adult↗