The Effect of Surgeon Volume on Revision for Periprosthetic Joint Infection: An Analysis of 602,919 Primary Total Knee Arthroplasties.

BACKGROUND: Periprosthetic joint infection (PJI) is a devastating complication of total knee arthroplasty (TKA). An association between low surgeon volume and higher rates of infection following primary TKA has been suggested. The purpose of the present study was to determine if there was a relationship between surgeon volume and the rate of revision for infection after primary TKA. METHODS: We searched the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) to identify all primary TKA procedures that were performed for the treatment of osteoarthritis from September 1, 1999, to December 31, 2020, and were subsequently revised because of infection. Surgeon volume was defined as the annual volume of procedures performed by a surgeon during the same year in which the primary TKA (which was subsequently revised for infection) was performed. Surgeon volume was defined as <25, 25 to 49, 50 to 74, 75 to 99, or ≥100 primary TKA procedures/year. The cumulative percent revision (CPR) for infection was determined with use of Kaplan-Meier estimates. Cox proportional hazards methods were used to compare rates of revision for infection by surgeon volume, with subanalyses for patellar resurfacing and polyethylene use. Further analyses for patients <65 years of age and male patients were undertaken. RESULTS: Overall, 602,919 primary TKA procedures were performed for the treatment of osteoarthritis, of which 5,295 were revised because of infection. High-volume surgeons (≥100 TKAs/year) had a significantly lower rate of revision for infection, with a CPR at 1 and 19 years of 0.4% (95% confidence interval [CI], 0.3 to 0.4) and 1.5% (95% CI, 1.2 to 2.0), respectively, compared with 0.6% (95% CI, 0.5 to 0.7) and 2.1% (95% CI, 1.8 to 2.3), respectively, for low-volume surgeons (<25 TKAs/year). Hazard ratios (HRs), adjusted for age and sex, comparing these 2 groups varied, depending on the time point, between 3.07 (95% CI, 2.02 to 4.68) and 1.44 (95% CI, 1.26 to 1.63) but remained significant (p < 0.001). When the analysis was adjusted for age, sex, American Society of Anesthesiologists (ASA) classification, and body mass index (BMI), there remained an increased risk of revision for PJI for all lower surgeon volume levels in comparison with the high- surgeon-volume group (≥100 TKAs/year). The results were similar when stratified by patellar resurfacing and cross-linked polyethylene (XLPE) and adjusted for age and sex. CONCLUSIONS: High-volume surgeons had lower rates of revision for infection. A better understanding of how surgical volume contributes to decreasing this complication is important and requires in-depth study. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Oxygen dynamics in shelf seas sediments incorporating seasonal variability.

Shelf sediments play a vital role in global biogeochemical cycling and are particularly important areas of oxygen consumption and carbon mineralisation. Total benthic oxygen uptake, the sum of diffusive and faunal mediated uptake, is a robust proxy to quantify carbon mineralisation. However, oxygen uptake rates are dynamic, due to the diagenetic processes within the sediment, and can be spatially and temporally variable. Four benthic sites in the Celtic Sea, encompassing gradients of cohesive to permeable sediments, were sampled over four cruises to capture seasonal and spatial changes in oxygen dynamics. Total oxygen uptake (TOU) rates were measured through a suite of incubation experiments and oxygen microelectrode profiles were taken across all four benthic sites to provide the oxygen penetration depth and diffusive oxygen uptake (DOU) rates. The difference between TOU and DOU allowed for quantification of the fauna mediated oxygen uptake and diffusive uptake. High resolution measurements showed clear seasonal and spatial trends, with higher oxygen uptake rates measured in cohesive sediments compared to the permeable sediment. The significant differences in oxygen dynamics between the sediment types were consistent between seasons, with increasing oxygen consumption during and after the phytoplankton bloom. Carbon mineralisation in shelf sediments is strongly influenced by sediment type and seasonality.

Prevalence, incidence, and risk factors for shoulder and neck dysfunction after neck dissection: A systematic review.

INTRODUCTION: Shoulder pain and dysfunction may occur following neck dissection among people being treated for head and neck cancer. This systematic review aims to examine the prevalence and incidence of shoulder and neck dysfunction after neck dissection and identify risk factors for these post-operative complications. METHODS: Electronic databases (Pubmed, CINAHL, EMBASE, Cochrane) were searched for articles including adults undergoing neck dissection for head and neck cancer. Studies that reported prevalence, incidence or risk factors for an outcome of the shoulder or neck were eligible and assessed using the Critical Review Form - Quantitative Studies. RESULTS: Seventy-five articles were included in the final review. Prevalence rates for shoulder pain were slightly higher after RND (range, 10-100%) compared with MRND (range, 0-100%) and SND (range, 9-25%). The incidence of reduced shoulder active range of motion depended on surgery type (range, 5-20%). The prevalence of reduced neck active range of motion after neck dissection was 1-13%. Type of neck dissection was a risk factor for shoulder pain, reduced function and health-related quality of life. CONCLUSIONS: The prevalence and incidence of shoulder and neck dysfunction after neck dissection varies by type of surgery performed and measure of dysfunction used. Pre-operative education for patients undergoing neck dissection should acknowledge the potential for post-operative shoulder and neck problems to occur and inform patients that accessory nerve preservation lowers, but does not eliminate, the risk of developing musculoskeletal complications.

Effect of textured insoles on balance and gait in people with multiple sclerosis: an exploratory trial.

OBJECTIVES: To investigate the immediate effects of textured insoles on balance and gait in people with multiple sclerosis (MS), and to explore any effects after 2 weeks of wear. STUDY DESIGN: Within-session repeated-measures design with an exploratory follow-up period. SETTING: Hospital gait laboratory. PARTICIPANTS: Forty-six individuals with MS (34 females, 12 males), with a mean (SD) age of 49 (7) years, who could walk 100m unassisted or using one stick/crutch. INTERVENTION: Participants were tested wearing three types of insoles in a random order: control (smooth), Texture 1 (Algeos) or Texture 2 (Crocs™). Participants were allocated at random to wear one type of textured insoles for 2 weeks, after which they were retested. MAIN OUTCOME MEASURES: Standing balance (centre of pressure excursions and velocity) was measured with eyes open and eyes closed on a Kistler force platform. Spatio-temporal parameters of gait were measured using a GAITRite system. RESULTS: The textured insoles had no significant immediate effects on balance or gait, apart from an increase in anteroposterior sway range with eyes open for Texture 2 insoles [mean difference 4.5 (95% confidence interval 0.6 to 8.4)mm]. After 2 weeks, balance was not significantly different, but both types of textured insoles showed significant effects on spatio-temporal parameters of gait, with mean stride length increases of 3.5cm (Texture 1) and 5.3cm (Texture 2) when wearing the insoles. CONCLUSIONS: After 2 weeks of wear, there were improvements in spatio-temporal parameters of gait. However, it is unclear whether this was a placebo effect or a learning effect.

Effects of clinically relevant alumina ceramic wear particles on TNF-alpha production by human peripheral blood mononuclear phagocytes.

The recent introduction of microseparation of the components of ceramic-on-ceramic hip prostheses during hip simulations has produced clinically relevant wear rates, wear patterns and wear particles. This provided an opportunity to determine the response of primary human peripheral blood mononuclear cells to clinically relevant alumina ceramic wear particles in vitro. Alumina ceramic wear particles were generated in a hip joint simulator under microseparation conditions. The particles showed a bi-modal size distribution with nanometer sized (5-20nm) and larger particles (0.2->10 micrometer). The particles were cultured with human peripheral blood mononuclear cells obtained from six different donors at particle volume to cell number ratios of 1, 10, 100 and 500 micrometer(3). After 24h incubation the viability of the cells and the levels of TNF-alpha were determined. The response to the microseparation wear particles was compared to that of commercially available alumina powder with a uniform morphology and mean size of 0.5 micrometer. All six Donors PBMNC produced significantly elevated levels of TNF-alpha when stimulated with 100 micrometer(3) of the alumina powder per cell. Volumetric concentrations of 10 and 1.0 micrometer(3) per cell failed to stimulate a significant response by the cells from any of the six donors. Three of the six Donors PBMNC secreted significantly elevated levels of TNF-alpha when stimulated with 100 micrometer(3) of the microseparation wear particles, whereas the other three failed to respond to the wear debris at this concentration. All of the Donors PBMNC produced significantly elevated levels of TNF-alpha when stimulated with 500 micrometer(3) of the microseparation wear particles per cell. Thus, a greater volume of the microseparation wear particles was required to activate the PBMNC than the alumina powder. This was probably due to the microseparation wear particles having fewer particles in the critical size range (0.1-1 micrometer) for macrophage activation compared to the alumina powder. It can be concluded that alumina ceramic wear particles generated under microseparation conditions are capable of inducing osteolytic cytokine production by human mononuclear phagocytes. However, the volumetric concentration of the particles needed to generate this response is extremely high and given the low wear rates (<4mm(3) per million cycles) of ceramic-on-ceramic bearings, even under severe microseparation conditions, it is unlikely that this concentration threshold will be achieved in vivo.

Comparison of the cytotoxicity of clinically relevant cobalt-chromium and alumina ceramic wear particles in vitro.

Concern over polyethylene wear particle induced aseptic loosening of metal-on-polyethylene hip prostheses has led to renewed interest in alternative materials such as metal-on-metal and alumina ceramic-on-alumina ceramic for total hip replacement. This study compared the effects of clinically relevant cobalt-chromium and alumina ceramic wear particles on the viability of U937 histiocytes and L929 fibroblasts in vitro. Clinically relevant cobalt-chromium wear particles were generated using a flat pin-on-plate tribometer. The mean size of the clinically relevant metal particles was 29.5+/-6.3 nm (range 5-200 nm). Clinically relevant alumina ceramic particles were generated in the Leeds MkII anatomical hip simulator from a Mittelmieier prosthesis using micro-separation motion. This produced particles with a bimodal size distribution. The majority (98%) of the clinically relevant alumina ceramic wear debris was 5-20 nm in size. The cytotoxicity of the clinically relevant wear particles was compared to commercially available cobalt-chromium (9.87 microm+/-5.67) and alumina ceramic (0.503+/-0.19 microm) particles. The effects of the particles on the cells over a 5 day period at different particle volume (microm(3)) to cell number ratios were tested and viability determined using ATP-Lite(TM). Clinically relevant cobalt-chromium particles 50 and 5 microm(3) per cell reduced the viability of U937 cells by 97% and 42% and reduced the viability of L929 cells by 95% and 73%, respectively. At 50 microm(3) per cell, the clinically relevant ceramic particles reduced U937 cell viability by 18%. None of the other concentrations of the clinically relevant particles were toxic. The commercial cobalt-chromium and alumina particles did not affect the viability of either the U937 histiocytes or the L929 fibroblasts.Thus at equivalent particle volumes the clinically relevant cobalt-chromium particles were more toxic then the alumina ceramic particles. This study has emphasised the fact that the nature, size and volume of particles are important in assessing biological effects of wear debris on cells in vitro.

Alumina-alumina artificial hip joints. Part I: a histological analysis and characterisation of wear debris by laser capture microdissection of tissues retrieved at revision.

The aims of this study were to investigate the tissues from uncemented Mittelmeier alumina ceramic-on-ceramic total hip replacements using histological methods and to isolate and characterise the ceramic wear debris using laser capture microdissection and electron microscopy. Tissues from around 10 non-cemented Mittelmeier alumina ceramic on ceramic THRs were obtained from patients undergoing revision surgery. Tissues were also obtained from six patients who were undergoing revisions for aseptic loosening of Charnley, metal-on-polyethylene prostheses. Tissue sections were analysed using light microscopy to determine histological reactions and also the location and content of alumina ceramic wear debris. Tissue samples were extracted from sections using laser capture microdissection and the characteristics of the particles subsequently analysed by TEM and SEM. The tissues from around the ceramic-on-ceramic prostheses all demonstrated the presence of particles, which could be seen as agglomerates inside cells or in distinct channels in the tissues. The tissues from the ceramic-on-ceramic retrievals had a mixed pathology with areas that had no obvious pathology, areas that were relatively rich in macrophages and over half of the tissues had in the region of 60% necrosis/necrobiosis. In comparison, the Charnley tissues showed a granulomatous cellular reaction involving a dense macrophage infiltrate and the presence of giant cells and < 30% necrosis/necrobiosis. The tissues from the ceramic prostheses also showed the presence of neutrophils and lymphocytes, which were not evident in the tissues from the Charnley retrievals. There were significantly more macrophages (p < 0.05), and giant cells (p < 0.01) in the Charnley tissues and significantly more neutrophils (p < 0.01) in the ceramic-on-ceramic tissues. TEM of the laser captured tissue revealed the presence of very small alumina wear debris in the size range 5-90 nm, mean size + SD of 24 +/- 19nm whereas SEM (lower resolution) revealed particles in the 0.05-3.2 microm size range. This is the first description of nanometre sized ceramic wear particles in retrieval tissues. The bi-modal size range of alumina ceramic wear debris overlapped with the size ranges commonly observed with metal particles (10-30 nm) and particles of ultra-high molecular weight polyethylene (0.1-1,000 microm). It is possible that the two size ranges of contributed to the mixed tissue pathology observed. It is speculated that the two types of ceramic wear debris are generated by two different wear mechanisms in vivo, under normal articulating conditions, relief polishing wear and very small wear debris is produced. while under conditions of microseparation of the head and cup and rim contact, intergranular and intragranular fracture and larger wear particles are generated.

Alumina-alumina artificial hip joints. Part II: characterisation of the wear debris from in vitro hip joint simulations.

Until recently it was not possible to reproduce clinically relevant wear rates and wear patterns in in vitro hip joint simulators for alumina ceramic-on-ceramic hip prostheses. The introduction of microseparation of the prosthesis components into in vitro wear simulations produced clinically relevant wear rates and wear patterns for the first time. The aim of this study was to characterise the wear particles generated from standard simulator testing and microseparation simulator testing of hot isostatically pressed (HIPed) and non-HIPed alumina ceramic-on-ceramic hip prostheses, and compare these particles to those generated in vivo. Standard simulation conditions produced wear rates of approximately 0.1 mm3 per million cycles for both material types. No change in surface roughness was detected and very few wear features were observed. In contrast, when microseparation was introduced into the wear simulation, wear rates of between 1.24 (HIPed) and 1.74 mm3 per million cycles (non-HIPed) were produced. Surface roughness increased and a wear stripe often observed clinically on retrieved femoral heads was also reproduced. Under standard simulation conditions only nanometre-sized wear particles (2-27.5 nm) were observed by TEM, and it was thought likely that these particles resulted from relief polishing of the alumina ceramic. However, when microseparation of the prosthesis components was introduced into the simulation, a bi-modal distribution of particle sizes was observed. The nanometre-sized particles produced by relief polishing were present (1-35nm). however, larger micrometre-sized particles were also observed by both transmission electron microscopy (TEM) (0.021 microm) and scanning electron microscopy (SEM) (0.05-->10 microm). These larger particles were thought to originate from the wear stripe and were produced by trans-granular fracture of the alumina ceramic. In Part I of this study, alumina ceramic wear particles were isolated from the periprosthetic tissues from around Mittelmeier ceramic-on-ceramic hip prostheses. Characterisation of the particles by TEM and SEM revealed a bi-modal size distribution. SEM analysis revealed particles in the 0.05-3.2 microm size range. and TEM revealed particles in the 5-90 nm size range, indicating that microseparation of the prosthesis components may be a common event in vivo. This study (Part II) has revealed that the introduction of microseparation of the prosthesis components during the swing phase of the wear simulation reproduced clinically relevant wear rates, wear patterns and wear particles in in vitro hip joint simulators.

A technique for the determination of trimethylamine-N-oxide in natural waters and biological media.

Trimethylamine-N-oxide (TMAO) is a nitrogenous osmolyte widely distributed in marine organisms. The reduction of TMAO to TMA has long been implicated as characteristic reaction associated with fish and seafood spoilage. However, it is now apparent that, in the marine environment, TMAO can act as precursor to a range of reduced nitrogenous biogases that can play a significant role in the biogeochemical cycle of nitrogen and in the regulation of atmospheric pH. Although methods exist for the analysis of TMAO in some biological samples, they lack the sensitivity required for measurement of TMAO in natural waters. Here we present a new, safe and sensitive method for the determination of TMAO in aqueous and biological media, where TMAO is enzymatically reduced to TMA and subsequently quantified using Flow Injection Gas Diffusion-Ion Chromatography (Gibb et al. J. Autom. Chem. 1995, 17 (6), 205-212). The limit of detection was calculated to be 1.35 nmol dm-3 TMAO, and the response was linear for both fresh and seawater (R2 = 0.996 and 0.993, respectively). Precision (RSD) for standards in the range 40-600 nmol dm-3 was within 3%. The specificity and competitive inhibition of the enzyme are addressed and the applicability of the technique demonstrated through analysis of a number of natural water and biological samples.

Mental health services in the county jail: a critical partnership?

This study was designed to provide a description of individuals incarcerated in a county jail and referred for mental health services. A standardized intake form was completed for 598 inmates who had contact with the mental health counselor. Analysis of the mental health status of inmates suggests that the presence of a counselor in the jail may serve an important function. Specifically, inmates referred to the counselor were not in acute distress. This suggests they may be better served by an on-site counselor rather than through the traditional method of being transported to the hospital emergency room or community mental health center for evaluation.

Trans-acting factors required for inclusion of regulated exons in the Ultrabithorax mRNAs of Drosophila melanogaster.

Alternatively spliced Ultrabithorax mRNAs differ by the presence of internal exons mI and mII. Two approaches were used to identify trans-acting factors required for inclusion of these cassette exons. First, mutations in a set of genes implicated in the control of other alternative splicing decisions were tested for dominant effects on the Ubx alternative splicing pattern. To identify additional genes involved in regulation of Ubx splicing, a large collection of deficiencies was tested first for dominant enhancement of the haploinsufficient Ubx haltere phenotype and second for effects on the splicing pattern. Inclusion of the cassette exons in Ubx mRNAs was reduced strongly in heterozygotes for hypomorphic alleles of hrp48, which encodes a member of the hnRNP A/B family and is implicated in control of P-element splicing. Significant reductions of mI and mII inclusion were also observed in heterozygotes for loss-of-function alleles of virilizer, fl(2)d, and crooked neck. The products of virilizer and fl(2)d are also required for Sxl autoregulation at the level of splicing; crooked neck encodes a protein with structural similarities to yeast-splicing factors Prp39p and Prp42p. Deletion of at least five other loci caused significant reductions in the inclusion of mI and/or mII. Possible roles of identified factors are discussed in the context of the resplicing strategy for generation of alternative Ubx mRNAs.

Generation of alternative Ultrabithorax isoforms and stepwise removal of a large intron by resplicing at exon-exon junctions.

Little is known about mechanisms that regulate and ensure accurate processing of complex transcription units with long introns. We investigate this in the Ultrabithorax gene of Drosophila. A consensus 5' splice site is regenerated at the junction between the first exon and a small internal exon (mI); this splice site is used in a developmentally regulated manner to remove mI during subsequent processing of the downstream intron. Conserved elements within mI and an interaction with exon mII modulate use of the regenerated splice site. Structural similarities predict the same process for mII. This resplicing mechanism avoids competition between distant splice sites for control of exon inclusion and allows removal of a 74 kb intron as a series of smaller fragments.

Comparison of anticoagulation regimens after Carpentier-Edwards aortic or mitral valve replacement.

BACKGROUND: To identify the optimal use of anticoagulants after Carpentier-Edwards valve replacement, a retrospective study of all patients undergoing Carpentier-Edwards aortic (N = 378) or mitral (N = 370) valve replacement was done. METHODS AND RESULTS: At the time of hospital discharge, 103 patients were managed with warfarin, 509 with aspirin alone, and 136 with no anticoagulation or antiplatelet therapy. Over the first 90 days after aortic or mitral valve replacement, the linearized rate of hemorrhage was greater for warfarin than for aspirin or no therapy (16.7 +/- 7.6%, 3.4 +/- 1.7%, and 3.1 +/- 3.1% per patient-year, respectively; P = .03). After aortic valve replacement, aspirin provided a low rate of thromboembolism (0.8 +/- 0.2% per patient-year), not significantly different from warfarin or no treatment (2.9 +/- 1.6% and 1.5 +/- 0.6% per patient-year) (P = .07). After mitral valve replacement, no single treatment was most advantageous because the rate of hemorrhage over the first 90 days for warfarin was equivalent to the 90-day rate of thromboembolism with aspirin or no therapy. CONCLUSIONS: Anticoagulation after Carpentier-Edwards mitral valve replacement may be best guided by individual patient characteristics. Within the limits of a retrospective analysis, these data support the routine use of aspirin alone after Carpentier-Edwards aortic valve replacement, both in the first 90 days and long-term.

Determinants of reoperation after 960 valve replacements with Carpentier-Edwards prostheses.

During the period of 1977 to 1990, 960 Carpentier-Edwards standard prostheses (Baxter Healthcare Corp., Santa Ana, Calif.) were placed in 875 operations. Freedom from reoperation at 10 years was 57% +/- 4%, 76% +/- 3%, and 95% +/- 5% for mitral, aortic, and tricuspid valve replacement, respectively. Age was the only independent determinant of reoperation for both aortic and mitral valves. Likelihood of reoperation decreased with age, with freedom from reoperation after 10 years in patients aged less than 60 years versus 60 or more years being 65% +/- 5% versus 90% +/- 4% after aortic valve replacement and 48% +/- 5% versus 75% +/- 6% after mitral valve replacement. For mitral valve replacement, larger valve size made reoperation more likely, with freedom from reoperation at 10 years being 71% +/- 6% for sizes median less than 31 mm and 57% +/- 5% for sizes 31 mm or larger. For aortic valve replacement, prior median sternotomy reduced freedom from reoperation at 10 years from 80% +/- 3% to 25% +/- 5%. The low prevalence of reoperation affirms the suitability of the Carpentier-Edwards prosthesis for selected elderly patients and for tricuspid valve replacement. Because of their influence on the probability of reoperation, valve size and prior cardiac procedures also merit consideration in the choice of valvular prosthesis.

Interactions between estrogens, androgens, progestins, and glucocorticoids in ZR-75-1 human breast cancer cells.

The human breast cancer cell line ZR-75-1 possesses androgen, estrogen, progesterone, and glucocorticoid receptors, thus offering a good model to study the specific role of each class of steroids in the control of breast cancer growth. Although the stimulatory action of classical estrogens (E2 and estrone) is well known, we have found a potent mitogenic effect of the adrenal estrogen androst-5-ene-3 beta,17 beta-diol (delta 5-diol) at concentrations within the range of those found in the serum of adult women, thus suggesting that delta 5-diol might be the most important estrogen in women. Androgens, on the other hand, exert a potent inhibitory effect on basal ZR-75-1 cell growth and completely reverse the stimulatory effect of estrogens on the same parameter. The antiproliferative effect of androgens was completely prevented by the antiandrogen OH-FLU, thus suggesting an action mediated by the androgen receptor. Part of the effect of androgens can be explained by the marked inhibition of estrogen receptor binding and mRNA levels by androgens. The antiproliferative effect of androgens is additive to that exerted by antiestrogens. Progestins, on the other hand, exert a specific antiproliferative effect in the presence of estrogens, the effect of progestins being antagonized by the stimulatory action of insulin on cell growth. Medroxyprogesterone acetate (MPA), a compound frequently used in the treatment of breast cancer in women, exerts its main inhibitory action through an androgen receptor-mediated action, whereas its glucocorticoid-like activity could play an additional role at high concentrations. All four classes of steroids are present, to various extents, as lipophilic esters of long-chain fatty acids. It is of interest to mention that all steroids that inhibit ZR-75-1 breast cancer cell growth (androgens, progestins, and glucocorticoids) stimulate the secretion and mRNA levels of gross cystic disease fluid protein-15 (GCDFP-15), whereas estrogens have the opposite effects, thus suggesting that GCDFP-15 could well be a good marker for monitoring the response to androgens, progestins, and antiestrogens during the course of breast cancer therapy.

Inhibitory effect of estrogens on GCDFP-15 mRNA levels and secretion in ZR-75-1 human breast cancer cells.

In order to better understand the mechanisms responsible for the antagonism between steroids in human breast cancer cells, we have studied the effect of 17 beta-estradiol (E2), dihydrotestosterone (DHT), and dexamethasone (DEX) alone or in combination on the expression of the breast gross cystic disease fluid protein-15 (GCDFP-15) in ZR-75-1 cells. Incubation with E2 markedly decreased basal GCDFP-15 mRNA levels accompanied by a parallel inhibition of the secretion of this tumor marker, the estrogenic effect being exerted at a half-maximal concentration of about 44 pM E2. The inhibitory effect of E2 on GCDFP-15 expression was competitively reversed by the antiestrogen LY156758. In addition, 1 nM E2 inhibited the marked stimulation induced by 1 nM DHT or 300 nM DEX on GCDFP-15 mRNA accumulation and on the secretion of the glycoprotein. However, at the concentration used, E2 reversed by only 65% the stimulation achieved by the combination of DHT and DEX on GCDFP-15 mRNA levels. It is of interest to mention that the effect of DHT, DEX, and E2 on GCDFP-15 expression is opposite to the respective effect of each steroid on ZR-75-1 cell proliferation. The present data on the regulation of GCDFP-15 mRNA demonstrate an estrogen-induced inhibition of mRNA levels under physiological conditions, thus offering a unique opportunity to study the mechanisms involved in the down-regulation of gene expression by estrogens and to achieve a better understanding of the antagonism between estrogens, androgens, glucocorticoids, and progestins in breast cancer cells. Furthermore, GCDFP-15 could well be a good marker for monitoring the response to androgens and antiestrogens during the course of breast cancer therapy.

The role of contact resistance in skin burns.

Analytical predictions of temperature-time histories of skin contacts with a number of materials are presented. Comparison with available experimental results show that correlations are much improved if a contact resistance is included in the analysis. Some simple experiments are also presented which indicate that the contact resistance between skin and a hard surface for a moderate contact pressure is of the order of 1000 W/m2K.