Andrej Cör

Extensive metallosis and necrosis in failed prostheses with cemented titanium-alloy stems and ceramic heads

We describe three prostheses with cemented titanium-alloy stems and Al2O3 ceramic femoral heads which had to be revised after a mean period of implantation of 78 months. In each case, the neck of the prosthesis had been so severely worn that the profile was elliptical rather than circular. There was severe metallosis of the periprosthetic tissues. Metal particles isolated from the tissues were approximately one nanometre in size and the ratios of titanium, aluminium and vanadium in the particles were the same as in the original alloy. Histologically, the high concentration of metal particles masked the presence of high-density polyethylene (HDP) debris, but again particles about one nanometre in size were isolated from the tissues. The severe necrobiosis and necrosis noted were consistent with other reports of the presence of extensive wear particles in periprosthetic tissues. Wear is presumed to have occurred as a result of mismatch between the shape or size of the taper cone and the femoral head, or to changes in the geometry of loading due to migration of the cup. To facilitate early intervention, patients with this design of prosthesis should be monitored radiologically.

Expression of Ki-67 antigen and proliferative cell nuclear antigen in benign and malignant epithelial lesions of the larynx

In an attempt to analyse the proliferative activity in benign and malignant laryngeal epithelial lesions, and to determine the relationship to their histologic grade, we studied the expression of proliferative cell nuclear antigen (PCNA) and Ki-67 antigen on 20 squamous carcinomas, and on 30 biopsies of epithelial hyperplasia categorized according to the Kambic-Lenart classification into simple, abnormal, and atypical hyperplasias. In simple hyperplasia, both antibodies stained the nuclei of the occasional cells in the basal layer. In abnormal hyperplasia (mild dyplasia), positive cells occupied up to a third, and in atypical hyperplasia (moderate and severe dysplasia) they occupied from two-thirds to the entire epithelial thickness. In squamous carcinoma, we have found a statistically significant correlation between its grade and the percentage of Ki-67-(p < 0.01) and PCNA-(p < 0.00001) positive cells. Our results suggest that the proliferative fraction progressively increases with the degree of epithelial hyperplasia and the grade of carcinoma. We conclude that the patterns of immunoreactivity to PCNA and Ki-67 antigen correspond to the histologic grade of both benign and malignant epithelial lesions of the larynx. This method should be regarded as a useful adjunct to traditional histological techniques allowing more objective grading of benign and malignant epithelial lesions.

Isolation of polyacetal wear particles from periprosthetic tissue of isoelastic femoral stems

We analysed revised Mathys isoelastic polyacetal femoral stems with stainless-steel heads and polyethylene acetabular cups from eight patients in order to differentiate various types of particle of wear debris. Loosening of isoelastic femoral stems is associated with the formation of polyacetal wear particles as well as those of polyethylene and metal. All three types of particle were isolated simultaneously by tissue digestion followed by sucrose gradient centrifugation. Polyacetal particles were either elongated, ranging from 10 to 150 microm in size, or shred-like and up to 100 microm in size. Polyethylene particles were elongated or granules, and were typically submicron or micron-sized. Polyacetal and polyethylene polymer particles were differentiated by the presence of BaSO4, which is added as a radiopaque agent to polyacetal but not to polyethylene. This was easily detectable by back-scattered SEM analysis and verified by energy dispersive x-ray analysis. Two types of foreign-body giant cell (FBGC) were recognised in the histological specimens. Extremely large FBGCs with irregular polygonal particles showing an uneven, spotty birefringence in polarised light were ascribed to polyacetal debris. Smaller FBGCs with slender elongated particles shining uniformly brightly in polarisation were related to polyethylene. Mononucleated histiocytes containing both types of particle were also present. Our findings offer a better understanding of the processes involved in the loosening of polyacetal stems and indicate why the idea of isoelasticity proved to be unsuccessful in clinical practice.

The endothelin system mediates bone modeling in the late stage of orthodontic tooth movement in rats

The endothelin system is involved in orthodontic tooth movement (OTM). The aim of the study was to examine the role of ET-1, ET(A) and ET(B) in bone modeling during OTM in rats. Male Wistar rats (n=62) were divided into three groups: control animals (n=10; control group) without appliance, and two groups of experimental animals, which were applied a super-elastic closed-coil spring between the first left maxillary molar and the incisors and were treated daily with either TBC3214 (n=10; TBC3214 group) or with saline (n=42; appliance only group). TBC3214 is a highly selective antagonist on ET(A) receptors. The distance between teeth was measured on days 0 and 42. On days 0, 14, 28 and 42 animals of the appliance only group (n=8) were sacrificed and tissue samples were taken. Total RNA and protein contents were isolated. Gene expression levels of ET-1, ET(A) and ET(B) were assessed by means of relative RT-PCR. Protein levels of ET(A) and ET(B) were examined by immunoblotting. Ten animals of each group were sacrificed on day 42 and tissue samples were prepared for histological analysis. Alveolar bone volume, osteoblast and osteoclast volume were determined histomorphometrically. Gene expression levels of ET-1, ET(A) and ET(B) varied throughout the experiment and were significantly up-regulated on day 42 (p<0.001). The immunoreactivity of ET(A) and ET(B) significantly decreased on day 14 (p<0.001) and increased on day 28 (p<0.001). Alveolar bone volume was significantly higher in the TBC3214 group compared to the appliance only group (p<0.001). Osteoclast volume was significantly lower in the TBC3214 group compared to the appliance only group (p<0.05). Gene and protein expression levels of ET-1, ET(A) and ET(B) varied significantly during OTM, suggesting their different roles in the various stages of OTM. TBC3214 significantly increased alveolar bone volume and significantly decreased osteoclast volume, indicating that it decreased bone resorption in stage three of OTM. These data suggest that ET-1 increases osteoclastic bone resorption via ET(A) in the late stage of OTM.

Quantitative Pathology of Laryngeal Epithelial Hyperplastic Lesions

We studied 40 laryngeal biopsies samples in order to ascertain the reliability of light microscopical criteria for subdividing laryngeal epithelial hyperplastic lesions (EHL) and carcinoma in situ as well as to determine the relationship between proliferative activity of their epithelial cells and the histological grade. The biopsies were divided into four groups in accordance with the Kambic-Lenart classification: simple, abnormal and atypical hyperplasia and carcinoma in situ. 10 cases in each group were included. The morphometrical analysis was carried out by a semiautomatic image analysis system. The proliferative activity was determined by the high percentage of cell nuclear antigen (PCNA) and Ki-67 positive epithelial cells and with counting nucleolar organizer regions (Ag-NORs) per nucleus. Our results suggest that measuring the nuclear area of the basal cells. augmented with basaloid cells and carcinomatous cells, is the most useful morphometrical method of differentiating three types of laryngeal EHL and carcinoma in situ, while the proliferative activity progressively increased with the degree of epithelial hyperplasia. Morphometrical methods and proliferative activity should be regarded as useful in conjunction with the traditional histopathological methods allowing more of objective grading of EHL.

Is There an Association between Glomerular Density and Birth Weight in Healthy Humans

Accessible online at: http://BioMedNet.com/karger Dear Sir, It has been estimated that the total number of nephrons in the normal human population ranges from 300,000 to 1,200,000 or more per kidney [1–3]. Brenner et al. [2] and Brenner and Chertow [3] have hypothesized that individuals with fewer nephrons at birth are at higher risk of developing essential hypertension in later life and at enhanced risk of expression of renal disease. They further suggested that a congenital deficit of nephrons might be caused by intrauterine growth retardation, as it occurs in infants with low birth weight. Some studies have already confirmed this hypothesis by demonstrating that a low birth weight is associated with a reduction in the total number of nephrons [4], with more frequent development of arterial hypertension [5], and with a poor prognosis of some renal diseases [6–8]. The significance of nephron number is, therefore, now well appreciated. However, little is known about the glomerular density in the normal human kidney. It is not clear to what extent the glomerular density varies in healthy individuals and which factors influence the glomerular density in the normal human kidney. We, therefore, analyzed the glomerular density in autopsy kidney samples of presumably healthy individuals who died accidentally. We further wished to find out whether there is an association between birth weight and glomerular density in the normal human kidney. Our study included kidney autopsy samples of 20 presumably healthy individuals (7 women and 13 men, aged 18–25 years, mean age 21.5 years) who died accidentally and Fig. 1. Linear correlation and 95% confidence limits between birth weight and glomerular density in 20 healthy young individuals.

Epidermal Growth Factor Receptor, c-erbB-2 and p53 Overexpressions in Epithelial Hyperplastic Lesions of the Larynx

An immunohistochemical analysis of overexpression of epidermal growth factor receptor (EGFR), c-erbB-2, and p53 proteins was performed on 43 biopsies of laryngeal epithelial hyperplastic lesions (EHLL), classified according to the Kambic-Lenart classification, and in 11 cases of laryngeal carcinoma (SCCL). The aim of the present study was to determine whether there is a correlation between the staining patterns of these proteins and different grades of EHLL, and to reveal their possible prognostic value. We compared the staining patterns of atypical hyperplasia adjacent to cancer with the same type of lesions which have not turned malignant. p53 and EGFR overexpressions were detected in 28/54 (52%) and 33/54 cases (61%), respectively, and tend to increase with the degree of epithelial changes. The intensity of staining in various grades of EHLL adjacent to cancer was more pronounced than the same type of lesions which have not progressed to cancer. c-erbB-2 was weakly positive in the majority of cases, and changed from predominantly membranous in simple hyperplasia to cytoplasmic staining in abnormal and atypical hyperplasias. There was no significant statistic correlation between the amount of positive cells for all proteins and the grade of epithelial abnormalities. We conclude that the overexpression of each biomarker itself adds little predictive value over routine histomorphology, and cannot be regarded as a reliable prognostic factor for EHLL. However, the histologic characteristics of atypical hyperplasia together with the immunostaining patterns of EGFR and p53 up to two-thirds or more of the epithelial thickness could be considered a reliable pattern which correlates with the progression to cancer.

Chromosomes 7,17 polysomies and overexpression of epidermal growth factor receptor and p53 protein in epithelial hyperplastic laryngeal lesions

Purpose: To visualize directly a sequence of genetic changes underlying the entire spectrum of epithelial hyperplastic laryngeal lesions (EHLL) and laryngeal cancer by the use of non-isotopic in situ hybridization (ISH) for chromosomes 7 and 17 in correlation with overexpression of p53 protein and epidermal growth factor receptor (EGFR). The specific aim was to compare the results and prognostic significance between the two types of EHLL: isolated, mainly atypical hyperplasia or risky epithelium, and EHLL associated with squamous cell carcinoma (SCC). Patients and Methods: 59 tissue specimens of EHLL obtained from 34 patients, graded according to the Ljubljana classification into simple (SH), abnormal (AbH) and atypical hyperplasia (AtH), and carcinoma in situ (CIS) were included in the study. Non-fluorescent ISH for chromosomes 7 and 17 was performed by biotinylated α-satellite DNA probes. Immunohistochemical staining for EGFR and p53 protein was analyzed on the same tissue samples. Results: Polysomy for both chromosomes increased in correlation with progressive grades of EHLL. The most important finding was the statistically significant difference in chromosome copy numbers between the isolated AtH and AtH associated with SCC. Overexpression of EGFR and p53 protein was found in 61 (36/59) and 52% (31/59) of cases, respectively. The immunoreactivity for both markers increased with the grade of lesions, but the staining pattern was not so uniform in isolated EHLL. On the other hand, the immunoreactivity was expressed more constantly in EHLL adjacent to SCC. Conclusions: Numerical changes in chromosomes 7 and 17 might be associated with an upregulation of EGFR and p53 genes, and could contribute to critical events in laryngeal carcinogenesis. For daily practice, the cytogenetic and immunohistochemical analyses could be of assistance in distinguishing between low- and high-risk groups of AtH. However, the isolated forms of atypical hyperplasia need considerable further study by evaluating genetic changes with the described methods regarding their ultimate transformation to carcinoma.

Effect of cetirizine, a histamine (H1) receptor antagonist, on bone modeling during orthodontic tooth movement in rats

INTRODUCTIONnHistamine (H(1)) receptor antagonists are widely used drugs for treatment of allergic conditions. Although histamine was shown to be involved in bone remodeling, the aim of this study was to determine the effects of cetirizine, an H(1) receptor antagonist, on bone modeling processes during orthodontic tooth movement.nnnMETHODSnWe used 3 groups of Wistar rats: control group (nxa0= 16), appliance-only group (nxa0= 16) and cetirizine group (nxa0= 16). Each animal of the last 2 groups was fitted with a superelastic closed-coil spring appliance and treated daily with saline solution or cetirizine. Tooth movement was measured weekly from day 0 to day 42. Gene expression levels for bone turnover markers cathepsin K and osteocalcin were determined by means of real-time polymerase chain reaction. Histologic samples were analyzed by using histomorphometry.nnnRESULTSnCetirizine decreased the amount of tooth movement from day 28 onward (Pxa0<0.01), and it also decreased osteoclast volume density (Pxa0<0.001). An increase in alveolar bone volume density was observed in the cetirizine group (Pxa0<0.01) compared with the appliance-only group. No statistically significant differences were observed in osteoclast activity, osteoblast volume density, and osteoblast activity between the cetirizine and the appliance-only groups.nnnCONCLUSIONSnCetirizine influences bone modeling, mainly by inhibiting bone resorption. Therefore, H(1) receptor antagonists could interfere with orthodontic treatment.

Unilateral ligature-induced periodontitis influences the expression of neuropeptides in the ipsilateral and contralateral trigeminal ganglion in rats

OBJECTIVESnExpression of neuronal neuropeptides in inflammatory conditions is altered. The changes in expression of substance P (SP) and calcitonin gene-related peptide (CGRP) in ipsilateral and contralateral trigeminal ganglion (TG) neurons were investigated by immunohistochemistry one week after unilateral ligature-induced periodontitis in rats.nnnDESIGNnA retrograde nerve tracer Fluorogold (FG) was applied into the gingival sulcus of the second maxillary molar to identify the neurons in TG that specifically innervate the inflamed gingivomucosa. In addition, neurons from the corresponding maxillary and the adjacent mandibular-ophthalmic regions in TG were analysed.nnnRESULTSnStatistically significantly higher frequencies of CGRP-positive neurons, regardless of their size, were found in TG ipsilateral to the periodontitis (83% and 73% in FG-labelled and maxillary regions, respectively) than in the control group without periodontitis (52% and 42% in FG-labelled and maxillary regions, respectively). The frequency of small FG-labelled SP-positive neurons in the ipsilateral TG (60%) was significantly higher than in the control TG (25%). In the contralateral TG the frequency of CGRP-positive neurons in maxillary region (66%) was significantly higher than in the control group. Surprisingly, the number of SP-positive neurons in all regions of contralateral TG decreased when compared to control and ipsilateral TGs.nnnCONCLUSIONSnTaken together, these results implicate a role of neurogenic component in the pathogenesis of periodontitis. The contralateral response in the TG could be mediated through the transmedian neurological pathways crossing in the trigeminal nuclear complex or through the systemic inflammatory reaction and the activation of the so called neuro-immune axis.