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N Marcussen

Publications and source records attributed to N Marcussen.

At least 55 records · Page 3Linked to original sources
PubMed1993

The number of glomerular capillaries estimated by an unbiased and efficient stereological method.

A method for unbiased capillary number estimation based on the estimation of the Euler-Poincaré characteristic or Euler number with the disector is evaluated. The generation of a new capillary creates a new loop in the capillary network corresponding to a change of exactly one unit in the Euler number of the network. In this way the Euler number has a one-to-one relationship to the number of capillaries in a network. In this report rat glomerular capillaries are counted. Three tissue blocks from each of 14 perfusion-fixed rat kidneys, aged between 5 days and 18 months, were uniformly sampled and embedded in Epon. Two complete glomerular profiles were sampled per block. Three consecutive sections were studied per glomerulus using the middle one to evaluate the topological events of the capillaries in the sampled glomerulus. The use of complete glomerular profiles eliminated problems with the edges, whereas the disector ensured unbiased sampling in the third dimension. Estimates per animal were weighted averages over blocks, the weights being half the number of glomerular profiles in a section from a block. The number of capillaries in a glomerulus is the mean Euler number per disector volume multiplied by the mean volume of glomeruli obtained by the fractionator. The observed coefficient of variation between animals was 18.3% for the estimated number of capillaries per glomerulus, and the observed coefficient of error at the level of blocks within animals was 14.7%. The exact capillary number from the node-branch network of two reconstructed glomeruli equalled the capillary number obtained by the total Euler number from the same glomeruli. This shows in an applied example, as would be expected, that the estimation of capillary number using the Euler number is unbiased and independent of the direction of sectioning.

Aging↗
PubMed1992

The distal nephron is preferentially infiltrated by inflammatory cells in acute interstitial nephritis.

In acute interstitial nephritis (AIN), mononuclear cells invade the tubules (tubulitis). The segmental localization of tubulitis is not precisely known. To clarify this question, formalin-fixed kidney biopsy specimens from 13 patients with AIN were studied stereologically by identifying cortical tubules with segment-specific markers. The periodic acid-Schiff reaction, peanut lectin, and antibodies against Tamm-Horsfall protein and epidermal cytokeratins all applied to the same section were used to identify the proximal tubules (PTs), distal convoluted tubules, distal straight tubules, and the cortical collecting system (connecting tubules and cortical collecting ducts), respectively. Morphometrically, an estimate of the relative volume of the inflammatory cell infiltrates within each category of tubular segments was obtained. Inflammatory cells were infrequently found in PTs (1.2%) but were frequently localized in distal tubules and the cortical collecting system (7.6%). There was no difference in the amount of the inflammatory cell infiltrate within these segments. Re-examination of an electron microscopic study of AIN carried out in this laboratory revealed that mononuclear cells were rarely seen in convoluted PTs but were frequently observed in straight PTs and all segments distal to them. The observations indicate that it is the distal nephron which is primarily affected by inflammatory cell infiltration in AIN.

Acute Disease↗
PubMed1992

Analysis of cytodiagnostic urinalysis findings in 77 patients with concurrent renal biopsies.

We investigated the value of cytodiagnostic urinalysis in detecting and scoring the severity of the four types of renal lesions (glomerular, interstitial, tubular, and vascular). Both cytodiagnostic urinalysis and concurrent renal biopsy were performed in 77 patients (47 from native kidneys and 30 from transplants) and the scoring and findings assessed in a double-blinded fashion. Evaluation of the reproducibility for the counting of renal cells showed a low intraobserver and interobserver variation. Cytodiagnostic urinalysis correlated with the renal biopsy with respect to primary lesions in 42 (89%) of the native kidney cases, and in 23 (77%) of the transplant kidney cases. The accuracy of diagnosis of glomerular lesions in both native and transplanted kidneys was 0.91, and for acute rejection in transplanted kidneys, the accuracy of diagnosis was 0.73. Severity scores showed good correlation between cytodiagnostic urinalysis and renal biopsy in both transplanted and in native kidneys and cytodiagnostic urinalysis correlated well with the increase in creatinine levels. The most important components of cytodiagnostic urinalysis for the diagnosis of glomerular lesions were dysmorphic erythrocytes and proteinuria. The specificity and sensitivity of dysmorphic erythrocytes for a glomerular lesion were 0.89 and 0.88, respectively. In cases with biopsy-proven glomerular lesions, more severe changes were found by cytodiagnostic urinalysis when the biopsy showed proliferative lesions in the glomeruli than when normal glomeruli were found by light microscopy. Cytodiagnostic urinalysis has the advantage over renal biopsy that it can be repeated as often as necessary and thus allows observation of the development or regression of the renal lesion over time. We conclude that cytodiagnostic urinalysis is well correlated with the renal biopsy and that it provides valuable and quantitative information regarding the disease process in the kidney.

Adult↗
PubMed1992

The double disector: unbiased stereological estimation of the number of particles inside other particles.

A double-disector method for obtaining estimates of the number of particles inside other particles, illustrated by an estimation of the average cell number in a glomerulus, has been developed. The method is suitable for paraffin-embedded tissue because it does not require knowledge about the section thickness. Most importantly, the estimate is absolutely unaffected by tissue shrinkage. The average number of cells in a human glomerulus is 2850 whereas in rats it is 580.

Animals↗
PubMed1992

The progression of cisplatin-induced tubulointerstitial nephropathy in rats.

We have previously shown that administration of cisplatin to rats leads to chronic nephropathy with many atubular glomeruli. Using unbiased stereological and histochemical methods our purpose was to investigate the progression of renal structural changes, specifically the events preceding and following the formation of atubular glomeruli in rats after increasing total doses of cisplatin. After administration of cisplatin (2 mg/kg body weight i.p. once weekly) the animals were sacrificed 10 days, three, six, 10 and 20 weeks later. After 4 mg/kg the distal part of most proximal S3 segments appeared necrotic with a negative reaction for enzymes characteristic of brush border and mitochondria. After larger doses, atrophy (and possibly necrosis) was observed in clusters of cortical proximal and distal nephron segments corresponding to an increasing amount of non-functioning nephrons. Hypertrophy/hyperplasia of remaining uninjured nephrons and collecting ducts was observed. The stereological investigations showed an increasing number of atubular glomeruli with open capillaries or glomeruli connected to atrophic tubules with the total dose of cisplatin (30% and 40%, respectively, after 20 mg/kg). The percentage of glomeruli with damaged tubules was significantly higher in the juxtamedullary cortex compared with the superficial cortex. Sclerotic glomeruli were not observed. The findings suggest that a toxic destruction of most S3 segments leads to atrophy or disappearance of the corresponding nephrons with formation of atubular glomeruli, and that the remaining hypertrophic nephrons are connected to the few surviving or regenerated S3 segments.

Animals↗
PubMed1992

Atubular glomeruli and the structural basis for chronic renal failure.

The pathologic changes in chronic renal failure are heterogeneous and depend to some extent on the primary disease process. However, end-stage kidneys have many common features, and other factors than the primary disease may be operative in the progression. Hyperfiltration of still functioning glomeruli has (especially in rat studies) been shown to be followed by glomerular injury. This progressive glomerulosclerosis has been proposed as a mechanism for the continuous deterioration of renal function that is found in most chronically diseased kidneys. Increased glomerular capillary pressure and glomerular hypertrophy, and dietary factors have been invoked in the pathogenesis of the glomerulosclerosis. In several chronic renal diseases, including tubulointerstitial diseases, but also some primary glomerular diseases such as glomerulonephritis, the renal function correlated better with the changes in the tubules and interstitium than with glomerular changes detectable in simple 2-dimensional sections. The correlation between tubulointerstitial changes and renal insufficiency has been explained by obliteration of the postglomerular capillaries supposed to lead to a decreased glomerular blood flow or by reduced reabsorption of sodium chloride in atrophic or damaged proximal tubules with subsequent reduction of glomerular filtration via the tubuloglomerular feedback mechanism. Atubular glomeruli have been found in several, mainly tubulointerstitial disorders. Unbiased morphometrical methods have provided valuable quantitative data about the atubular glomeruli and about the structural renal changes in general. The atubular glomeruli constitute a significant and sometimes even a major part of the glomerular population in various chronic renal diseases. The atubular glomeruli are generally small, whereas glomeruli connected to normal proximal tubules have volumes at the normal level or above. Atubular glomeruli have open capillaries and minor ultrastructural changes and function as a pathway for blood that is delivered without prior filtration to the intertubular capillaries. This lack of filtration may explain the decreased filtration fraction seen in some renal diseases. Their fate in the chronically diseased kidney is not known but they have not been shown to be eliminated. They can only be identified using serial sections or microdissection. Correlation between the decrease in renal function and the decrease in percentage of glomeruli connected to normal proximal tubules have been found in experimental lithium and cisplatin nephropathy. The presence of atubular glomeruli explains the correlation between the volume of proximal tubules (and interstitium) on the one hand and the altered renal function on the other. The presence of atubular glomeruli also explains the irreversibility of chronic renal diseases.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Atubular glomeruli, renal function and hypertrophic response in rats with chronic lithium nephropathy.

Experimental lithium nephropathy was induced by administering lithium orally to newborn rats for 8 weeks; thereafter the rats were randomized into four groups which were studied after 8 weeks of further treatment. One group was left untreated, one group was given a high (40%) protein diet, one group was unilaterally nephrectomized and one group was unilaterally nephrectomized and received high protein diet after nephrectomy. Comparable control groups (not lithium-treated) were also studied. Stereological methods were used to estimate the total volume of different parts of the nephron, interstitial fibrosis, and the distribution of the volume of individual glomeruli. The structural integrity between the glomerulus and the proximal tubule was investigated on serial sections. No sclerotic glomeruli were present. The most extensive degree of hypertrophy with almost a doubling of the total volume of proximal and distal tubule cells was seen in the groups that were both nephrectomized and fed a high protein diet. In both controls and lithium-treated animals, high protein and nephrectomy induced enlargement of the glomerular tufts to volumes from 4 to 5 times the normal size. A pronounced heterogeneity of the glomerular population was found in the lithium-treated groups with 36-54% atubular glomeruli with small volumes, and 34-48% enlarged glomeruli connected to qualitatively normal proximal tubules. Only glomeruli connected to proximal tubules had a potential for hypertrophy. In multiple regression analysis the percentage of glomeruli connected to normal proximal tubules was correlated with the reciprocal of plasma creatinine, but the volume of fibrosis also contributed to the decreased renal function.

Animals↗
PubMed1991

Immunohistological demonstration of intermediate trophoblast in the diagnosis of uterine versus ectopic pregnancy: a retrospective survey and results of a prospective trial.

Immunohistological demonstration of human placental lactogen (hPL) in non-villous, mononuclear intermediate trophoblastic cells may be of routine diagnostic value, when chorionic villi are absent in endometrial curettings from patients suspected of miscarriage of an intrauterine pregnancy. The histological presence and distribution of hPL was investigated in endometrial curettings from 90 patients studied retrospectively (47 had ectopic pregnancies, 14 miscarriages, and 29 legal abortions), and a consecutive, prospective series of 50 patients (40 had miscarriages and 10 had ectopic pregnancies) without chorionic villi in their endometrial curettings. Non-specific background staining was not a problem. The retrospective survey disclosed that hPL was a highly sensitive marker of intrauterine pregnancy (sensitivity = 0.98). In the prospective series, the predictive value of positive staining for hPL for intrauterine pregnancy was 1.00, and the sensitivity of hPL, as an indicator of uterine gestation, was 0.62. In absence of specific hPL-staining, the risk of ectopic pregnancy was about 50%. The immunohistochemical demonstration of hPL is a useful tool for identifying patients who are suspected of having had a miscarriage, but for whom evidence in the form of chorionic villi in endometrial curettings is lacking.

Abortion, Spontaneous↗
PubMed1991

Atubular glomeruli in renal artery stenosis.

The aim of the present study was to investigate and quantitate the structural renal changes developing after stenosis of the renal artery. Twelve kidneys removed at operation from patients with elevated blood pressure due to stenosis of the renal artery were investigated together with three kidneys with renal artery stenosis but no clinical evidence of renovascular hypertension. Eight age-matched autopsy kidneys served as controls. Stereologic methods were used to estimate the volume fractions of different structural parameters, the volume of individual glomeruli, and the structural integrity between the glomerulus and the proximal tubule. In six of the kidneys with renal artery stenosis and in the controls, the total number of nonoccluded glomeruli was estimated. Immunohistochemical staining for epithelial membrane antigen, Tamm-Horsfall protein and lectin Arachis hypogaea was performed in order to determine whether the atrophic tubules in renal artery stenosis were of proximal or distal origin. The results showed that the volume fractions of both proximal and distal tubules had decreased in renal artery stenosis, whereas the volume fractions of the glomerular tufts and interstitium increased. Immunohistochemical staining indicated, however, that more distal than proximal tubules were preserved, although atrophic. In the kidneys with artery stenosis, very few glomeruli were seen connected to a normal proximal tubule; in 52% of the glomeruli Bowman's capsule did not open toward a tubule and 40% were connected to an atrophic tubule. The mean glomerular volume (uncorrected for shrinkage) of 1.5.10(6) microns3 in the kidneys with artery stenosis was significantly decreased compared with the 2.9.10(6) microns3 in the controls. The mean glomerular number was normal in the kidneys with artery stenosis. The study shows that despite the absence or severe atrophy of the tubules, the glomeruli are not destroyed but only smaller. More proximal than distal tubules are destroyed by the ischemic process.

Female↗
PubMed1990

Ultrastructural quantitation of atubular and hypertrophic glomeruli in rats with lithium-induced chronic nephropathy.

The very heterogeneous population of glomeruli in rats with lithium-induced chronic nephropathy which includes small glomeruli without connection to a proximal tubule (atubular glomeruli) and large hypertropic glomeruli with connection to a normal proximal tubule, was studied at the ultrastructural level, using stereological methods. After 8 weeks of lithium treatment followed by 8 weeks without lithium the hypertrophic glomeruli showed no changes in their relative ultrastructural composition, including normal mesangium, basement membrane-like material and peripheral basement membrane. The absolute quantities of each component were, however, increased due to the increased volume of the glomeruli. The atubular glomeruli had increased volume fractions of mesangium, peripheral basement membrane, basement membrane-like material and epithelium, whereas the absolute quantities were decreased due to the decreased volume. The thickness of the basement membrane was within normal limits in the group of hypertrophic glomeruli but increased by 31% above controls in the group of atubular glomeruli. Both groups of glomeruli in lithium-treated animals showed normal mean foot process width, but with a slightly abnormal distribution. The atubular glomeruli showed a disproportionate large decrease in peripheral filtration surface and capillary length, compared with the reduction in glomerular volume, whereas the hypertrophic glomeruli showed changes in proportion with the increased volume.

Animals↗
PubMed1990

Atubular glomeruli in cisplatin-induced chronic interstitial nephropathy. An experimental stereological investigation.

In two previous studies on chronic renal failure in humans as well as in experimental animals a large number of glomeruli were found not to be connected to proximal tubules (atubular). Using unbiased stereological methods the purpose of the present study was to investigate and quantitate various renal structures, including the presence or absence of atubular glomeruli, in chronic renal failure induced by cisplatin. After administration of cisplatin to rats for ten weeks, the left kidney was perfusion-fixed 3 weeks later. The cisplatin-treated rats were uremic with an average plasma urea of 32.6 mmol/l compared with 10.8 mmol/l in controls. The stereological investigations showed that 31% of the glomeruli in the cisplatin-treated group were atubular, 37% were connected to a normal proximal tubule and 32% to an atrophic tubule. Sclerotic glomeruli were not observed and the total number of glomeruli did not differ between the two groups. The mean glomerular volume was significantly decreased in the cisplatin group, and the mean volume of atubular glomeruli was lower than the mean volume of glomeruli connected to a normal proximal tubule. Significant negative correlation was found between the plasma urea on the one hand and the percentage of glomeruli connected to normal proximal tubules, as well as the length of normal proximal tubules, on the other hand. A significant positive correlation was found between plasma urea and the volume of interstitial fibrotic tissue. The presence of atubular glomeruli and the absence of compensatory hypertrophy of the remaining nephrons might be responsible for the reduction in kidney function in several chronic interstitial renal diseases.

Animals↗
PubMed1990

Atubular glomeruli in patients with chronic pyelonephritis.

In an animal model of chronic nephropathy a large proportion of the apparently normal glomeruli have been shown to be small and without connection to a proximal tubule. The present study examines the degree to which atubular glomeruli are also present in human renal disease. Eleven patients with chronic pyelonephritis (CP) and seven controls were investigated. The number of glomeruli connected to a normal proximal tubule was determined in serial sections and the volumes of individual glomeruli estimated with stereological methods. Only glomeruli with little or no sclerosis were investigated. The volume fractions of proximal tubules and interstitial tissue were estimated using point counting. The results showed that 50% of glomeruli in the CP group were connected to a normal proximal tubule, whereas 35% of the glomeruli were without any recognizable connection to a proximal tubule (atubular glomeruli). The remaining 15% were connected to an atrophic tubule. The mean volume of the glomeruli without a connection to a normal proximal tubule was only half that of glomeruli with a normal proximal tubule. No significant difference was found between the mean glomerular volume in the two groups, but the intraindividual variation of glomerular volumes was larger in the CP group. A significant negative correlation was found in the CP group between the percentage of glomeruli without connection to a normal proximal tubule and the volume fraction of proximal tubules. A significant positive correlation was found between the percentage of glomeruli that were not connected to a normal proximal tubule and the volume fraction of the interstitial tissue. This study shows that atubular glomeruli, which only can be identified in serial sections, constitute a large proportion of glomeruli in chronic pyelonephritis. Their existence could be a major reason for the irreversibility of nonglomerular chronic renal diseases.

Adolescent↗
PubMed1989

[Acute tonsillectomy in infectious mononucleosis].

Enlargement of the pharyngeal tonsils in infectious mononucleosis (MI) is frequently an important component of the clinical picture but pronounced obstruction of the upper respiratory passages is rare. An analysis of 11 cases of infectious mononucleosis with varying degrees of pharyngeal obstruction is presented. During the acute phase of the disease, tonsillectomy was performed and also adenoidectomy in four of the cases. The patients improved rapidly after the operation and were discharged after an average of four days. No noteworthy complications of the operation occurred. An unexpectedly great number of cases of abscess formation were found at operation. Histological examination of the tonsils revealed changes in the lymphoid tissue which were characteristic but not specific for infectious mononucleosis together with extensive necrosis of the tonsillar surface. On the basis of this investigation, the authors consider that acute tonsillectomy is indicated in infectious mononucleosis with threatening occlusion of the upper airway and in cases of suspected peritonsillar abscess. In cases of slight or moderate respiratory obstruction, acute tonsillectomy may be considered in the therapeutic deliberations if the course of the condition is protracted and steroid treatment does not have the desired effect.

Adenoidectomy↗
PubMed1989

[Non-specific granulomatous prostatitis].

Non-specific granulomatous prostatitis (NGP) is histologically defined and reported with an incidence below 3.4% in unselected series of patients. A survey of the literature concerning NGP is given on the basis of a retrospective investigation of 14 case-histories. Microscopically, NGP is characterized by focal or diffuse occurrence of granulomas in the prostate. The etiological significance has been attributed to acute non-specific prostatitis and local hypersensitivity and/or simple foreign-body reactions are considered to be pathogenetic factors. The mean age of patients suffering from NGP is stated to be 54-65 years. Clinically, NGP is poorly defined. Complaints of cystitis/urethritis within the last month and subsequently rapid development or aggravation of urinary obstruction are frequently reported on admission. On digital rectal examination the gland is enlarged, and carcinoma is often suspected. Fine-needle aspiration biopsy may be of some guidance. However, the diagnosis is settled postoperatively by histologic investigation, where prostatic cancer, iatrogenic granulomas and specific granulomatous inflammations must be considered as differential diagnoses. Irrespective the choice of treatment, conservative or surgery, the prognosis of NGP is excellent.

Aged↗
PubMed1989

Combined sarcoidosis and disseminated visceral giant cell vasculitis.

A middle-aged man with only slight symptoms of disease of short duration died suddenly. On autopsy he was found to have not only disseminated visceral giant cell vasculitis with involvement of large and medium-sized arteries and veins, but also sarcoid granulomas in many organs, especially in enlarged mediastinal lymph nodes as well as in several vessel walls. Death was caused by myocardial infarction due to granulomatous vasculitis. This combination of diseases has not previously been described, and the question is whether it represents giant cell arteritis and sarcoidosis, separately, or whether it is a manifestation of a broad spectrum of the same disease.

Arteritis↗
PubMed1989

Interstitial nephritis and glomerulonephritis in visceral leishmaniasis in a dog. A case report.

Renal involvement characterized by interstitial nephritis and glomerulonephritis is reported in a case of visceral leishmaniasis in a dog. Focal interstitial inflammatory infiltrates including lymphocytes and plasma cells together with collections of histiocytes containing Leishmania donovani organisms were found in the renal cortex. The glomeruli showed diffuse mesangial cell proliferation, thickening of the capillary wall and focal, segmental glomerulosclerosis. By electron microscopy, finely granular electron dense deposits were shown in subendothelial, intramembranous as well as subepithelial locations. It is suggested that the interstitial nephritis was caused by the presence of parasitic elements in the renal interstitium, whereas the glomerular involvement may have been due to deposition of antigen-antibody complexes.

Animals↗
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↗