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Biomedical subjects

S Olsen

Publications and source records attributed to S Olsen.

At least 19 recordsLinked to original sources

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

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

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

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

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

Histological evaluation of prostatic cancer. (III): Reproducibility of assessment of tumour volume and its possible significance for prognosis.

The aim of this study was to evaluate the INTER- and INTRA-observer reproducibility of prostatic cancer volume defined as the percentage of chips with carcinoma in transurethrally resected tissue. All histological slides from 80 consecutive cases of prostatic cancer were blindly evaluated on two independent occasions by each of four pathologists. The correlation was expressed by Spearman's rank correlation coefficient (R). Both the overall INTER- and mean INTRA-observer correlation of tumour volume were high with R being respectively 0.905 and 0.918. With reference to stage A1 and A2, data were transformed to an ordinal scale with 2 categories (less than = 5%, greater than 5%). The overall INTER- and mean INTRA-observer agreement of this classification were 0.926 and 0.943 respectively--the corresponding kappa coefficients being 0.68 and 0.74. It is concluded that in transurethrally resected tissue a highly reproducible index of the resected prostatic cancer volume can be given by the percentage of chips with tumour. The prognostic significance of this parameter is discussed.

Humans

In vitro antiplaque effects of a triclosan/copolymer mouthrinse.

The influence of a mouthrinse containing 0.03% triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether) and 0.25% copolymer (polyvinylmethylether maleic acid copolymer), compared to a matching placebo rinse, on in vitro plaque formation was assessed in two dynamic plaque model systems. In the controlled saliva flow cell system, the triclosan-containing rinses significantly reduced total plaque compared to the placebo rinse, with no significant differences when copolymer was removed from the active rinse formula. In the continuous culture system (chemostat flow cell model), the mean plaque was significantly reduced when compared with placebo. The results of these studies indicate that a triclosan mouthrinse, in the presence or absence of copolymer, is effective in reducing plaque in vitro.

Bacteria

Antiplaque effects of dentifrices containing triclosan/copolymer/NaF system versus triclosan dentifrices without the copolymer.

A dentifrice containing triclosan/PVM/MA, Colgate Gum Protection Formula Toothpaste (GPF), was found to be highly effective against oral bacteria with minimal inhibitory concentration ranging from 0.3 to 5.35 micrograms/ml. A variety of in vitro model systems simulating oral environment were used to compare dentifrices containing triclosan/PVM/MA versus the dentifrices containing triclosan without PVM/MA, such as Crest Gum Health Toothpaste (CGH) and Neo-Mentadent P Toothpaste (N-MP). The uptake of triclosan on saliva-coated hydroxyapatite (HA) disks and buccal epithelial cells was significantly higher from the GPF versus the other dentifrices. Uptake on HA disks was 132 micrograms/disk versus 11 micrograms/disk from CGH; on buccal epithelial cells the uptake was 59 micrograms/2 x 10(5) cells with GPF versus 30.0 micrograms with CGH per same number of cells. The retained triclosan on the surfaces provided a sustained and higher antibacterial effect up to 4 hours post-treatment with GPF, but not with N-MP and CGH. In dynamic plaque model systems such as the chemostat or the controlled saliva flow system, GPF was significantly (P = 0.05) more effective than N-MP or CGH in reducing plaque thickness, protein and carbohydrate contents of plaque films. Collectively, the results of these microbiological and biochemical investigations indicate that the GPF has the potential to provide superior clinical efficacy versus the dentifrices without the copolymer.

Dental Plaque

Primary acute renal failure ("acute tubular necrosis") in the transplanted kidney: morphology and pathogenesis.

"Acute tubular necrosis" (ATN) in the transplanted kidney, when properly differentiated from other causes of acute renal failure, appears to be a relatively benign condition. It has been widely assumed to be pathologically identical to ATN in the native kidney, but its histopathologic features have not been studied in detail. Because immunosuppressive therapy with cyclosporine adds an additional layer of complexity to the morphologic changes observed, in the present study we have confined our observations to patients immunosuppressed with steroids and azathioprine. Thirteen renal allograft biopsies from patients with ATN and 5 biopsies from patients with normal allograft function were compared with the previously obtained series of 57 native kidney ATN biopsies and 20 control biopsies. Both qualitative and quantitative differences between transplant and native kidney ATN were found. Compared with native kidney ATN, transplant ATN showed significantly less thinning and absence of proximal tubular brush border and less variation in size and shape of cells in individual tubular cross-sections. There were also significantly fewer casts and less dilatation of Bowman's space and a significantly greater number of polarizable crystals presumed to be oxalate in transplant ATN. In native kidney ATN the tubular injury sites were mostly characterized by desquamation of individual epithelial cells leaving areas of bare basement membrane (the "non-replacement" phenomenon). In transplant ATN, sites of tubular injury, although rare and affecting only short tubular segments, were characterized by the actual presence of identifiable necrotic tubular cells, a finding seldom seen in native kidney ATN. There also was a greater interstitial infiltrate of mononuclear inflammatory cells in transplant ATN compared to native kidney ATN. Electron microscopic studies of 9 transplant ATN biopsies showed a mild reduction in proximal tubular brush border compared with controls but this alteration was significantly less than that observed in native kidney ATN. There was no significant alteration in proximal or distal basolateral infoldings and this contrasted sharply with the marked reduction in basolateral infoldings of the plasma membrane observed in native kidney ATN. Disintegrated necrotic cells were found by electron microscopy in transplant ATN whereas these were not observed in native kidney ATN. There were significantly more cells with apoptosis (shrinkage necrosis) in transplant ATN than in native kidney ATN. There were significantly more cells with apoptosis (shrinkage necrosis) in transplant ATN than in native kidney ATN. On the other hand, there were significantly greater numbers of "non-replacement" sites in the distal tubules in native kidney ATN compared to transplant ATN.(ABSTRACT TRUNCATED AT 400 WORDS)

Actins

Reproducibility of histomorphologic diagnoses with special reference to the kappa statistic.

Systems for classification and grading used in pathology should ideally be biologically meaningful and at least be reproducible from one pathologist to another. A statistical method to evaluate reproducibility (non-chance agreement) for several observers using nominal or ordinal categories has been developed and refined over the past few decades--the kappa statistic. A high level of observed agreement among different pathologists can either signify a high level of reproducibility, if agreement by chance is low, or express a low level of reproducibility, if agreement by chance is almost as high as the observed agreement. Therefore, the observed agreement says nothing in itself, unless it is low. The kappa value, however, indicates how much better the observers are compared to a throw of the dice, and therefore gives the real credit to the agreement which was found. We have developed a user-friendly computer program for calculating inter- and intra-observer agreement of 2 or more observers. By calculating associations between different categories and different observers, the statistic furthermore obtains a function close to the parameter of accuracy. We recommend the use of the above method before a set of nominal or rank scale parameters are used for deciding prognosis and treatment of patients. By submitting a diskette the computer program will be available at no cost.

Histological Techniques

Histological evaluation of prostatic cancer. 1. Reproducibility of tumour type.

It has been claimed that the histological type of prostatic carcinoma bears influence on the prognosis of the patient, and that different treatments have to be considered for different types of tumours. The primary aim of this study was to evaluate the reproducibility of the histological criteria for the ordinary acinic adenocarcinoma and ductal adenocarcinoma. From 85 prospective and consecutive cases of prostatic carcinoma all histological slides were examined on two independent occasions by each of 4 pathologists. The overall inter observer agreement and mean intra observer agreement were 0.69 and 0.74, respectively. The kappa coefficients of these inter and mean intra observer agreements were 0.39 (S.E. = 0.02) and 0.48 (S.E. = 0.08), respectively. Considering a dichotomous classification of pure acinic versus all other types of prostatic carcinoma, an overall inter observer agreement of 0.78 and mean intra observer agreement of 0.84 were found. The kappa coefficients of this dichotomous classification were 0.51 (S.E. = 0.03, inter) and 0.61 (S.E. = 0.11, intra), respectively. It is concluded that the criteria for differentiation between different histological types of prostatic carcinoma need to be improved.

Carcinoma

[Clinical pathology of the glomerulus--from phenomenon to entity. The nodular-lobular lesion].

The nodular lesion in renal glomeruli develops as a localized accentuation of mesangial volume augmentation. First described by Kimmelstiel and Wilson in 1936, it was soon accepted as the characteristic form of glomerular sclerosis in patients with long-term diabetes mellitus. It has for a long time been recognized that lesions very similar to nodular glomerulosclerosis may rarely occur in patients without diabetes. Clinical and pathological investigations of such cases have shown that glomerular nodules can also develop, 1. as a sequal to light chain deposit disease associated with plasma cell dyscrasia (e.g. myelomatosis), 2. in mesangioproliferative and membranoproliferative glomerulonephritis ("lobular" GN) and 3. in some cases of glomerular amyloid deposition. A survey is given of the characteristic light microscopy, ultrastructure and immunopathology of the glomerular nodules in these diseases. The differential diagnosis and pathogenesis is discussed.

Amyloidosis

Evaluation of a procedure for systematic semiquantitative analysis of glomerular ultrastructure in human renal biopsies.

A method is described for systematic semiquantitative investigation of glomerular ultrastructure in renal biopsies from patients with glomerulonephritis. Three glomeruli per biopsy were studied by electron microscopy. Ten systematically recorded micrographs at x12,000 and a montage covering the whole glomerular cross-section at x3,000 were analyzed from each glomerulus. The severity of each of 34 different ultrastructural lesions was semiquantitatively evaluated on a 4-degree scale, 0 to +++. The usefulness of the method was evaluated by calculating different parameters for the reproducibility of semiquantitative scoring, representativeness of micrographs, and representativeness of glomeruli. The reliability of the method was considered good or acceptable with respect to 17 of the lesions. Ten lesions obtained a high reproducibility of scoring but the usefulness of the scores was limited due to a segmental and/or focal distribution of these lesions. The evaluation of these lesions can be improved by analyzing a larger number of micrographs, or glomeruli, or both. Seven lesions were so rare in the present biopsies that no statistical evaluation was possible. When applied to a large number of biopsies, this practical and useful method allows a reproducible comparison of the patterns of ultrastructural lesions in various types of glomerulonephritis.

Basement Membrane