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S Olsen

Publications and source records attributed to S Olsen.

At least 73 records · Page 4Linked to original sources
PubMed1994

Cyclosporin A nephropathy: standardization of the evaluation of kidney biopsies.

An advisory board of nephropathologists with personal experience in the evaluation of biopsies from patients treated with cyclosporin A (CyA) was set up to address the following problems: 1. Definition of CyA nephropathy as seen in patients with autoimmune diseases; 2. Evaluation of the reliability and reproducibility of the diagnostic criteria for the different morphological lesions seen in CyA nephropathy; 3. Classification of the morphological lesions according to their clinical relevance; 4. Estimation of the possible progression of CyA nephropathy with continuous CyA therapy. The most frequent lesions attributable to CyA therapy in patients with autoimmune diseases are tubular atrophy, interstitial fibrosis, and arteriolar hyalinosis. All other lesions are rare. The reproducibility and diagnostic reliability is high for tubular atrophy and interstitial fibrosis, but low for arteriolar lesions even among experienced nephropathologists. The biopsies may be classified according to the severity of tubular atrophy, interstitial fibrosis and arteriolar hyalinosis with regard to their clinical relevance: In group I (within normal limits), CyA therapy can be continued; in group III (moderate-to-severe CyA-related lesions), CyA should be stopped if possible. Among group II biopsies (slight CyA-related abnormalities), no recommendation can be made in the absence of a second biopsy after a further year of CyA therapy. No clear-cut answer can be given concerning the progression of CyA-induced lesions. However, no significant progression has been found in the cases studied to date.

Adolescent↗
PubMed1994

Qualitative and quantitative histopathology in transitional cell carcinomas of the urinary bladder. An international investigation of intra- and interobserver reproducibility.

BACKGROUND: Histopathologic, prognosis-related grading of malignancy by means of morphologic examination in transitional cell carcinomas of the urinary bladder (TCC) may be subject to observer variation, resulting in a reduced level of reproducibility. This may confound comparisons of treatment results. Using objective, unbiased stereologic techniques and ordinary histomorphometry, such problems may be solved. EXPERIMENTAL DESIGN: A study of 110 patients with papillary or solid transitional cell carcinomas of the urinary bladder in stage Ta through T4 was carried out, addressing reproducibility of both qualitative and quantitative grading methods. Grading of malignancy was performed by one observer in Japan (using the World Health Organization scheme), and by two observers in Denmark (using the Bergkvist system). A "translation" between the systems, grade for grade, and kappa statistics were used in evaluating the reproducibility. Unbiased estimates of nuclear mean volume, nuclear mean profile area, nuclear volume fraction, nuclear profile density index, and mitotic profile density index were obtained twice in 55 of the studied cases by one observer in Japan and one in Denmark, using a random, systematic sampling scheme. RESULTS: The results were compared by bivariate correlation analyses and Kendall's tau. The international interobserver reproducibility of qualitative gradings was rather poor (kappa = 0.51), especially for grade 2 tumors (kappa = 0.28). Likewise, the interobserver agreement on the Bergkvist scheme was poor (kappa = 0.43). On the other hand was the interobserver agreement on invasion high (kappa = 0.75). The intraobserver reproducibility of the quantitative histopathologic variables was excellent in both Japan and Denmark for estimates of nuclear mean volume (r = 0.93), for nuclear mean profile area (0.78 < r < 0.83), and for nuclear profile density index (0.85 < r < 0.89), whereas the reproducibility for nuclear volume fraction was somewhat poorer (0.68 < r < 0.64). The slopes of the correlation lines were not significantly different from unity. Estimates of mitotic profile density index also showed acceptable intraobserver reproducibility (Kendall's tau > 0.53). CONCLUSIONS: The international, interobserver reproducibility of the quantitative estimators yielded similar results for all histopathologic variables investigated, except for nuclear volume fraction (r = 0.54). This can probably be related to the manual design of the sampling scheme and may be solved by introducing a motorized object stage in the systematic selection of fields of vision for quantitative measurements. However, the nuclear mean size estimators are unaffected by such sampling variability. The results obtained in this study stress the need for objective, quantitative histopathologic techniques substituting qualitative, subjective methods in prognosis-related grading of malignancy.

Adult↗
PubMed1993

Quantitative histopathology in the prognostic evaluation of patients with transitional cell carcinoma of the urinary bladder.

BACKGROUND: Morphologic grading of malignancy is considered to be of prognostic value in patients with transitional cell carcinomas of the urinary bladder (TCC). This qualitative approach is, however, associated with low reproducibility. Grading of malignancy can be carried out on a reproducible, quantitative scale. METHODS: A retrospective, prognostic study of 110 patients treated for TCC in clinical Stages Ta-T4 (median follow-up time, 6 years) was performed, evaluating various grading techniques. Unbiased estimates of the volume-weighted mean nuclear volume (nuclear vV), nuclear volume fraction, estimates of nuclear mean profile area (aH(nuc)), nuclear profile density index (NI), and mitotic profile density index (MI) were obtained by stereologic and morphometric techniques. RESULTS: The T-stage and morphologic grade of malignancy were closely cross-correlated (+0.63 < Kendall tau < +0.71, 2P < 6.7 x 10(-16)). The estimation of nuclear vV was highly efficient, with more than 85% of the associated variation attributable to differences between tumors. A positive significant correlation between estimates of nuclear vV and aH(nuc) was detected (r = +0.79), whereas an inverse correlation was documented between nuclear vV and NI (r = -0.63). Estimates of nuclear volume fraction showed no correlation with nuclear vV. Comparisons between categorical and quantitative data revealed the following: a decrease in averaged estimates of NI for tumors in advanced T-stage and malignancy grade (2P < 0.0008); and nuclear vV and aH(nuc) increased on average, in tumors of high T-stage and malignancy grade. Estimates of MI were also positively correlated with the T-stage and the malignancy grade (+0.42 < Kendall tau < +0.49). Single-factor analyses showed prognostic effect of T-stage, grade of malignancy, and, apart from nuclear volume fraction, all quantitative histopathologic variables with regard to overall survival (2P < 0.03). None of the morphometric and stereologic parameters were of prognostic values with regard to recurrence-free survival (2P > 0.26). Multiple hazards regression analysis (Cox models) revealed that clinical stage of disease was the sole independent prognostic variable. Only estimates of nuclear vV added significant independent prognostic prediction with regard to recurrence-free survival in the 48 patients with Ta tumors (2P = 0.03). CONCLUSIONS: The results suggested that estimates of nuclear vV are prognostically superior to morphologic grading of malignancy in noninvasive TCC, whereas both morphologically and quantitatively based malignancy grading are without prognostic value in invasive TCC.

Adult↗
PubMed1993

Pituitary as a target organ for toxic effects of P4501A1 inducing chemicals.

We report here that cytochrome P4501A1 in the male rainbow trout pituitary is highly inducible by beta-naphthoflavone. Pituitary cells containing inducible P4501A1 were identified by double immunostaining as gonadotrophs containing gonadotropin II. Thus, the pituitary gonadotrophs may be target cells for polyaromatic hydrocarbons. Elevated plasma levels of gonadotropin II (GTH II) and testosterone in the induced fish indicated that the functioning of the pituitary was disturbed. Because GTH II regulate the final stage of sexual maturation the results implies that exposure to P4501A1 inducing compounds may disturb this development stage.

Animals↗
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↗
PubMed1993

Segmental localization and quantitative characteristics of tubulitis in kidney biopsies from patients undergoing acute rejection.

The term tubulitis denotes infiltration of the renal tubular epithelium by mononuclear cells. Tubulitis is one of the most reliable signs of acute renal allograft rejection. However, its segmental localization and quantitative characteristics are not precisely known. To investigate this question, formalin-fixed kidney biopsy specimens from 15 patients with transplanted allografts undergoing acute rejection 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 profiles of proximal tubules (PTs), distal convoluted tubules (DCTs), distal straight tubules (DSTs), and the cortical collecting system (CCS, connecting tubules and cortical collecting ducts), respectively. Two parameters, the relative intrasegmental length and the average intensity of tubular damage, were determined to describe the degree of tubulitis quantitatively. Tubulitis was most prominent in the DCTs, followed by the CCS. The average intensity of tubulitis was lowest in the DSTs. The results indicate that the PTs are not the main site of tubulitis, despite the fact that they are regarded primary targets of the rejection response.

Adolescent↗
PubMed1993

Classification of tubulo-papillary renal cortical tumours using estimates of nuclear volume.

The classification of renal cortical tumours is problematic, with no clear division of benign from malignant tumours. Unbiased stereological estimates of volume-weighted nuclear volume (nuclear vv) were obtained by point sampling of nuclear intercepts in a retrospective study of 36 variably sized tubulo-papillary basophilic cell renal cortical tumours. There was no clear pattern of evolution of nuclear vv with increasing macroscopic tumour diameter. Estimates of nuclear vv could not distinguish between 21 tumours classified as renal adenomas with macroscopic diameters < 3 cm (average nuclear vv = 241 microns 3) and 15 tumours classified as renal cell carcinomas with diameters > 3 cm, or aggressive histological pattern (average nuclear vv = 229 microns 3) (2p = 0.68). In this subtype of renal cortical tumours, estimates of nuclear vv do not support the historical convention of using a 3 cm tumour diameter as the dividing line between adenomas and carcinomas, but support the theory of a single group of tumours. As most of the truly incidental renal cortical tumours are less than 1 cm in diameter, this limit could be considered. Such small benign cortical nodules have never been reported to metastasize, and would thus be excluded from being diagnosed and registered as malignant. Although this dividing line is again arbitrary, and cannot be justified by the stereological measurements, it is a practical solution to a clinical problem. There were too few examples of disease progression to assess the prognostic significance of nuclear vv in these tumours.

Adenoma↗
PubMed1992

Morphologic renal changes during cyclosporine treatment of psoriasis. Studies on pretreatment and posttreatment kidney biopsy specimens.

BACKGROUND: Because of concern about long-term renal toxicity from low-dose cyclosporine therapy, we studied kidney biopsy specimens in psoriasis patients treated with this drug. OBJECTIVE: The purpose of the study was to investigate whether any morphologic changes appear after approximately 1 year of treatment. METHODS: Pretreatment and posttreatment renal biopsy specimens were performed in 12 psoriasis patients treated with cyclosporine in dosages from 1.8 to 6 mg/kg/day for 6 to 18 months. RESULTS: The study disclosed a slight but significant increase in interstitial fibrous tissue, which negatively correlated with creatinine clearance. The findings were similar to those described in patients receiving higher dosages of cyclosporine. CONCLUSION: The clinical relevance of these so-far minor changes is unknown and does not exclude the use of cyclosporine in severe psoriasis; however, they should be taken into consideration in so-called low-dose therapy.

Adult↗
PubMed1992

Oral bioavailability and anti-simian varicella virus efficacy of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) in monkeys.

BV-araU (1-beta-D-arabinofuranosyl-E-5-[2-bromovinyl]uracil) has potent antiviral activity against varicella zoster virus in cell culture and is undergoing clinical evaluation. In the present study, pharmacokinetic parameters and the efficacy of BV-araU against infection with simian varicella virus (SVV) were evaluated in African green monkeys. Pharmacokinetic parameters were determined by analysis of the BV-araU content of sera obtained after oral and intravenous administration to normal monkeys. Peak serum concentrations showed dose proportionality, with the 0.1 mg/kg dose resulting in a peak serum concentration of 0.05 micrograms/ml, the approximately ED50 value for the SVV inoculum in cell culture. BV-araU administered orally twice daily at 0.1 mg/kg for 10 days starting 48 h after intratracheal SVV infection prevented vesicular rash development and suppressed viremia. Effective therapy could be initiated 96 h after infection. Taken together, these results indicate that BV-araU is effective oral therapy at doses that achieve peak serum levels equivalent to the ED50 for SVV in cell culture.

Administration, Oral↗
PubMed1992

Binding of a cementum attachment protein to extracellular matrix components and to dental surfaces.

Cementum proteins (CP) have been shown to mediate cell attachment. Among these, a 55 kDa protein was isolated. The purpose of the present study was to assess the capacity of CP to bind to non-demineralized and demineralized root surfaces and to support cell attachment to dentin. CP were prepared by sequential extraction of bovine cementum with 25 mM EDTA, 0.5 M acetic acid followed by 4 M guanidine HCl. The latter was subjected to ion exchange chromatography on a DEAE-3SW column and eluted stepwise with a 0-0.5 M NaCl gradient. CP were labelled with 125I and the capacity of 125I-CP to bind to mineralized and partially demineralized dentin, synthetic hydroxyapatite, collagen, fibronectin and fibrillar collagen-fibronectin complex was assessed. It was found that CP bind specifically to mineralized dentin and synthetic hydroxyapatite but not to demineralized dentin. The specific binding was 60% of the total binding. SDS-PAGE analysis of the proteins bound to dentin indicated that the main bound protein had a molecular weight of 55 kDa. CP exhibited high affinity for fibronectin (kD = 1.56 x 10(-10) M) and fibronectin-collagen complex, but their binding to either molecular or fibrillar collagen was negligible. It is suggested that CP may play an important role in the attachment of cells of the periodontium to cementum extracellular matrix during homeostasis and regeneration.

Animals↗
PubMed1991

Influence of an anticalculus mouthrinse treatment on the dentition and periodontium in beagle dogs.

This research evaluated the effect of an anticalculus mouthrinse, containing 3.3% pyrophosphate anion and 1.0% of a copolymer of vinylmethyl ether and maleic acid (Gantrez), on calculus formation, gingivitis, gingival recession, and epithelial attachment in beagle dogs over a one-year period of time, compared to a distilled water rinse. Each was applied twice a day for the one-year period. Compared to the control, the anticalculus mouthrinse resulted in significant reductions in the formation of calculus and gingivitis, as well as a prevention of loss of epithelial attachment in the beagle dogs. The results from this investigation suggest that it is possible to mitigate both probing epithelial attachment loss and increases in probing pocket depth at the calculus prone sites through the use of an anticalculus mouthrinse.

Analysis of Variance↗
PubMed1990

Histological evaluation of prostatic cancer. (II): Reproducibility of a histological grading system.

The aim of this study was to evaluate the reproducibility, expressed by kappa coefficients, of the histological grading system of prostatic cancer as proposed by Schroeder, Hop, Blom and Mostofi in 1985. This grading system has five prognostic groups based on combinations of growth pattern, mitoses and nuclear anaplasia. All histological slides from 85 cases of prostatic carcinoma were blindly evaluated on two independent occasions by each of four pathologists. The overall INTER-observer agreement and mean INTRA-observer agreement regarding "prognostic group" were 0.55 and 0.69 respectively, whereas the kappa coefficients were 0.38 and 0.57 respectively. An acceptable level of INTER-observer reproducibility of prognostic group I (kappa = 0.70), of the parameter "growth pattern" (kappa = 0.60) and of "slight nuclear anaplasia" (kappa = 0.62) was found. A low overall kappa coefficient of "mitoses" and "nuclear anaplasia" was found. Based on the well reproducible parameters a simplified grading system is proposed.

Anaplasia↗