Hydroxylapatite-coated total prosthesis of the hip

Since 1987, 80 hydroxyapatite-coated (HA) cementless total hip prostheses have been implanted. Thirty patients were examined 21 months postoperatively and the results compared with data for uncoated prosthesis. Earlier mobilization and freedom from pain, together with evidence of bone ingrowth without connective tissue membrane formation, confirmed the benefits of HA-coated prostheses.     

Ultrastructural determinants of murine achilles tendon strength during healing

The mechanisms by which tendon strength is established during growth and development and restored following injury are not completely understood and are likely to be complex, multifactorial processes. Several studies examining the relationship between mechanical behavior and ultrastructural characteristics of tendons and ligaments during growth and maturation suggest that collagen fibril diameter is strongly correlated with tendon strength. Because of the similarities between development and repair processes of musculoskeletal tissues, increases in tendon strength during healing may be related to increases in fibril ultrastructural parameters such as fibril size, numerical density, and area fraction. In this study, we compared murine Achilles tendons at various time points after tenotomy with sham-operated controls in tensile tests to failure and examined tendons using electron microscopy to assess collagen fibril ultrastructure. We found that in the 6-week period following Achilles tenotomy, fibril mean diameter remained significantly smaller than sham-side diameter by a factor of 2-3. Despite the persistently small fibril size, increasing numerical density resulted in a gradual increase in fibril area fraction. Biomechanical strength did not reach that of intact tendons until some time between 5 and 7 weeks, approximately the same time period when fibril area fraction began to approach sham values. These data suggest that parameters other than collagen fibril size are most responsible for increased tendon strength during healing.     

CD105 expression as a measure of microvessel density in supraglottic laryngeal squamous cell carcinoma

The purpose of the present study was to examine the expression of CD105 among patients with supraglottic laryngeal cancer and to assess the clinical relevance of CD105-assessed MVD. A total of 40 patients with supraglottic squamous cell carcinomas (SCCs) were included in the present study. Surgical specimens were immunostained for CD105 and MVD was calculated at 400× magnification. The rounded mean value of the vessel count in four fields for each case was used as the final MVD value. The mean MVD value assessed by CD105 in considered supraglottic SCCs was 13.5 (SD = 3.97). High MVD was significantly correlated with advanced (III and IV) clinical stage (Mann–Whitney U test P = 0.01) and malignancy recurrence presence/absence (Mann–Whitney U test P = 0.023). Spearman’s rank correlation test showed significant correlation between high CD105-assessed MVD and pN+ category (rho = 0.337, P = 0.033), advanced Stage (III and IV) (rho = 0.402, P = 0.01) and developed locoregional recurrence (rho = 0.395, P = 0.012). The logistic regression showed that a high CD105+ MVD was the only independent marker of tumor recurrence (P = 0.029; odds ratio, 6.64; 95% CI, 1.218–36.152). The average MVD was significantly higher in patients with advanced TNM stage and in patients with locoregional recurrence of disease, suggesting that angiogenesis is closely related with clinical aggressiveness of tumor. CD105-assessed MVD in supraglottic laryngeal SSCs may identify patients at risk of recurrence of disease.     

Statistics of assay validation in high throughput cell imaging of nuclear factor kappaB nuclear translocation

This report describes statistical validation methods implemented on assay data for inhibition of subcellular redistribution of nuclear factor kappaB (NF kappaB) in HeLa cells. We quantified cellular inhibition of cytoplasmic-nuclear translocation of NF kappaB in response to a range of concentrations of interleukin-1 (IL-1) receptor antagonist in the presence of IL-1alpha using eight replicate rows in each four 96-well plates scanned five times on each of 2 days. Translocation was measured as the fractional localized intensity of the nucleus (FLIN), an implementation of our more general fractional localized intensity of the compartments (FLIC), which analyzes whole compartments in the context of the entire cell. The NF kappaB antagonist assay (inhibition of IL-1- induced NF kappaB translocation) data were collected on a Q3DM (San Diego, CA) EIDAQtrade mark 100 high throughput microscopy system. [In 2003, Q3DM was purchased by Beckman Coulter Inc. (Fullerton, CA), which released the IC 100 successor to the EIDAQ 100.] The generalized FLIC method is described along with two-point (minimum-maximum) and multiple point titration statistical methods. As a ratio of compartment intensities that tend to change proportionally, FLIN was resistant to photobleaching errors. Two-point minimum-maximum statistical analyses yielded the following: a Z' of 0.174 with the data as n = 320 independent well samples; Z' by row data in a range of 0.393-0.933, with a mean of 0.766; by-plate Z' data of 0.310, 0.443, 0.545, and 0.794; and by-plate means of columns Z' data of 0.879, 0.927, 0.945, and 0.963. The mean 50% inhibitory concentration (IC50) for IL-1 receptor antagonist over all experiments was 213 ng/ml. The combined IC50 coefficients of variation (CVs) were 0.74%, 0.85%, 2.09%, and 2.52% for the four plates. Repeatability IC50 CVs were as follows: day to day 3.0%, row to row 8.0%, plate to plate 2.8%, and day to day 0.6%. The number of cells required for statistically resolvable differences in dose concentrations, plotted in a family of FLIN sigma/deltamicro (SD/range) curves and tabulated, demonstrated cell-by-cell assay precision with our combined sigma/deltamicro = 0.32 that required approximately 10-fold fewer cells than in a previously reported NF kappaB assay with sigma/deltamicro = 1.52. To better understand the relationship between cell-by-cell measurements and IC50 precision, 500 Monte Carlo simulations with varying cell-measurement SDs were used to explore three-, five-, seven-, and 11-point model titrations. The reductions in deltaIC50 90% confidence intervals from 11- to three-point titrations were 10-fold with the previously reported sigma/deltamicro = 1.52 and twofold with our sigma/deltamicro = 0.32. With these normalized parameters, this report provides a common statistical foundation, independent of the assay details, for evaluating the performance of imaging data on any instrument.     

High-concentration contrast media in multiphasic abdominal multidetector-row computed tomography: effect of increased iodine flow rate on parenchymal and vascular enhancement

OBJECTIVE: The purpose of this study was to assess the influence of the iodine flow rate on parenchymal and vascular enhancement during multiphasic abdominal multidetector-row computed tomography (MDCT). METHODS: Fifteen patients underwent MDCT at an iodine flow rate of 1.2 g/s as well as 1.6 g/s (group A, protocols 1 and 2), and 90 patients underwent MDCT at an iodine flow rate of 1.2 g/s (group B) or 1.6 g/s (group C). Measurements were performed for all groups in the liver, spleen, pancreas, portal vein, inferior vena cava, and abdominal aorta. RESULTS: Aortal and pancreatic enhancement during the arterial phase was significantly higher with the higher iodine flow rate. The mean difference in aortal enhancement was 60 Hounsfield units (HU) between protocols 1 and 2 of group A, and the mean difference was 70 HU between groups B and C. The mean difference in pancreatic enhancement was 10 HU between protocols 1 and 2 of group A and 17 HU between groups B and C. During the portal and hepatic venous phases, no significant difference in enhancement was observed. CONCLUSION: A high iodine flow rate in multiphasic abdominal MDCT improves enhancement of the aorta and the pancreas during the arterial phase but does not influence later phases.     

The analysis of clinical characteristics of the chronic rhinosinusitis: complicated and uncomplicated form

The objective of our study was to analyze the intensity of subjective symptoms and objective findings of endoscopy and CT scanning in chronic rhinosinusitis, in the groups with and without nasal polyps. To evaluate the intensity of subjective symptoms visual analogue scale (VAS) was used, while scores were obtained by adding grades. Endoscopic finding was given in scores recommended by Lanza and Kennedy and CT results were presented by Lund-Mackay scoring system. The study included 90 consecutive adult patients, 47 males (52%) and 43 females (48%), mean age 45 years. The group with chronic rhinosinusitis without nasal polyps (uncomplicated form) consisted of 30 patients, while the group with polyps (complicated form) included 60 patients. Comparing mean intensity values of all subjective symptoms between these two groups we found out that nasal obstruction, nasal secretion and hyposmia were significantly more manifested in the polyp group (P < 0.01). Facial congestion was also more manifested in the polyp group (P < 0.05). Mean score value of major symptoms was 35.55 in the polyp group, and 23.13 in the group without polyps (P < 0.01). Mean value of total symptom scores was 48.68 in the polyp group, and 35.00 in the group without polyps (P < 0.01). Endoscopic score was approximately 9.03 in the polyp group, and 2.43 in the group without polyps (P < 0.01). CT score was 16.05 on an average in the polyp group, and 4.37 in the group without polyps (P < 0.01). Chronic rhinosinusitis complicated by nasal polyposis is characterized by higher degree of nasal obstruction, nasal secretion, hyposmia and facial congestion, which results in higher score of major and total score of symptoms, respectively. This form is also characterized by worse objective findings, which is reflected in higher endoscopic and CT scores.     

Differential effects of embryonic immobilization on the development of fibrocartilaginous skeletal elements

The importance of mechanical influences during skeletal development has been well established in both experimental studies and computer models. Under conditions of embryonic immobilization, it has been observed that the early stages of joint formation proceed normally (up to and including interzone formation), but the later stages of joint cavitation and maintenance are impaired, resulting in fusion of the cartilaginous elements across the presumptive joint line. Two structures in particular are noticeably absent from late-stage synovial joints in immobilized chick embryos: the menisci of the tibiofemoral joint and the plantar tarsal sesamoid of the tibiotarsal joint. Both of these fibrocartilaginous structures are known to serve mechanical functions in postnatal animals, helping to distribute loads within the joint and, in the case of sesamoid structures, to provide a mechanical advantage to muscles acting across the joint. We demonstrate in this study that embryonic immobilization differentially affects the developmental fate of these two distinct fibrocartilages. The absence of the plantar tarsal sesamoid in late-stage immobilized embryos is due to a failure in the initial formation of this structure. In contrast, the early stages of meniscus formation proceed normally. Without the normal mechanical stimuli of skeletal muscle contractions, however, the meniscus fails to mature and ultimately degenerates.     

Spinal muscular atrophy among the Roma (Gypsies) in Bulgaria and Hungary

Spinal muscular atrophy is one of the most common autosomal recessive disorders, classified into three major clinical forms. It is caused mainly by deletions or gene conversions of the telomeric survival motor neuron gene (SMN1) on human chromosome 5. We have conducted molecular studies of the disorder in genetically isolated Romani (Gypsy) communities in Bulgaria and Hungary, where spinal muscular atrophy appears to have different prevalence and both mild and severe spinal muscular atrophy phenotypes have been diagnosed. We have observed three distinct genetic defects which, in different combinations, lead to different forms of the disease. The similar chromosomal background on which the different mutations occur suggests a common origin and founder effect, with rearrangements of a single ancestral chromosome resulting in a diversity of molecular defects.