Projected increase in total knee arthroplasty in the United States - an alternative projection model.

OBJECTIVE: The purpose of our study was to estimate the future incidence rate (IR) and volume of primary total knee arthroplasty (TKA) in the United States from 2015 to 2050 using a conservative projection model that assumes a maximum IR of procedures. Furthermore, our study compared these projections to a model assuming exponential growth, as done in previous studies, for illustrative purposes. METHODS: A population based epidemiological study was conducted using data from US National Inpatient Sample (NIS) and Census Bureau. Primary TKA procedures performed between 1993 and 2012 were identified. The IR, 95% confidence intervals (CI), or prediction intervals (PI) of TKA per 100,000 US citizens over the age of 40 years were calculated. The estimated IR was used as the outcome of a regression modelling with a logistic regression (i.e., conservative model) and Poisson regression equation (i.e., exponential growth model). RESULTS: Logistic regression modelling suggests the IR of TKA is expected to increase 69% by 2050 compared to 2012, from 429 (95%CI 374-453) procedures/100,000 in 2012 to 725 (95%PI 121-1041) in 2050. This translates into a 143% projected increase in TKA volume. Using the Poisson model, the IR in 2050 was projected to increase 565%, to 2854 (95%CI 2278-4004) procedures/100,000 IR, which is an 855% projected increase in volume compared to 2012. CONCLUSIONS: Even after using a conservative projection approach, the number of TKAs in the US, which already has the highest IR of knee arthroplasty in the world, is expected to increase 143% by 2050.

Increased risk of revision for high flexion total knee replacement with thicker tibial liners.

The outcome of total knee replacement (TKR) using components designed to increase the range of flexion is not fully understood. The short- to mid-term risk of aseptic revision in high flexion TKR was evaluated. The endpoint of the study was aseptic revision and the following variables were investigated: implant design (high flexion vs non-high flexion), the thickness of the tibial insert (≤ 14 mm vs > 14 mm), cruciate ligament (posterior stabilised (PS) vs cruciate retaining), mobility (fixed vs rotating), and the manufacturer (Zimmer, Smith & Nephew and DePuy). Covariates included patient, implant, surgeon and hospital factors. Marginal Cox proportional hazard models were used. In a cohort of 64 000 TKRs, high flexion components were used in 8035 (12.5%). The high flexion knees with tibial liners of thickness > 14 mm had a density of revision of 1.45/100 years of observation, compared with 0.37/100 in non-high flexion TKR with liners ≤ 14 mm thick. Relative to a standard fixed PS TKR, the NexGen (Zimmer, Warsaw, Indiana) Gender Specific Female high flexion fixed PS TKR had an increased risk of revision (hazard ratio (HR) 2.27 (95% confidence interval (CI) 1.48 to 3.50)), an effect that was magnified when a thicker tibial insert was used (HR 8.10 (95% CI 4.41 to 14.89)). Surgeons should be cautious when choosing high flexion TKRs, particularly when thicker tibial liners might be required.

Risk factors associated with surgical site infection in 30,491 primary total hip replacements.

We examined patient and surgical factors associated with deep surgical site infection (SSI) following total hip replacement (THR) in a large integrated healthcare system. A retrospective review of a cohort of primary THRs performed between 2001 and 2009 was conducted. Patient characteristics, surgical details, surgeon and hospital volumes, and SSIs were identified using the Kaiser Permanente Total Joint Replacement Registry (TJRR). Proportional-hazard regression models were used to assess risk factors for SSI. The study cohort consisted of 30,491 THRs, of which 17,474 (57%) were performed on women. The mean age of the patients in the whole series was 65.5 years (13 to 97; SD 11.8) and the mean body mass index was 29.3 kg/m(2) (15 to 67; SD 5.9). The incidence of SSI was 0.51% (155 of 30,491). Patient factors associated with SSI included female gender, obesity, and American Society of Anesthesiologists (ASA) score ≥ 3. Age, diagnosis, diabetes and race were not associated with SSI. The only surgical factor associated with SSI was a bilateral procedure. Surgeon and hospital volumes, use of antibiotic-laden cement, fixation method, laminar flow, body exhaust suits, surgical approach and fellowship training were not associated with risk of SSI. A comprehensive infection surveillance system, combined with a TJRR, identified patient and surgical factors associated with SSI. Obesity and chronic medical conditions should be addressed prior to THR. The finding of increased SSI risk with bilateral THR requires further investigation.

Development of porous PEG hydrogels that enable efficient, uniform cell-seeding and permit early neural process extension.

Three-dimensional polymer scaffolds are useful culture systems for neural cell growth and can provide permissive substrates that support neural processes as they extend across lesions in the brain and spinal cord. Degradable poly(ethylene) glycol (PEG) gels have been identified as a particularly promising scaffold material for this purpose; however, process extension within PEG gels is limited to late stages of hydrogel degradation. Here we demonstrate that earlier process extension can be achieved from primary neural cells encapsulated within PEG gels by creating a network of interconnected pores throughout the gel. Our method of incorporating these pores involves co-encapsulating a cell solution and a fibrin network within a PEG gel. The fibrin is subsequently enzymatically degraded under cytocompatible conditions, leaving behind a network of interconnected pores within the PEG gel. The primary neural cell population encapsulated in the gel is of mixed composition, containing differentiated neurons, and multipotent neuronal and glial precursor cells. We demonstrate that the initial presence of fibrin does not influence the cell-fate decisions of the encapsulated precursor cells. We also demonstrate that this fabrication approach enables simple, efficient and uniform seeding of viable cells throughout the entire porous scaffold.

Homozygosity and linkage disequilibrium mapping of autosomal recessive distal myopathy (Nonaka distal myopathy).

Autosomal recessive distal myopathy or Nonaka distal myopathy (NM) is characterized by its unique distribution of muscular weakness and wasting. The patients present with spared quadriceps muscles even in a late stage of the disease. The hamstring and tibialis anterior muscles are affected severely in early adulthood. We have localized the NM gene to the region between markers D9S319 and D9S276 on chromosome 9 by linkage analysis. To further refine the localization of the NM gene, we conducted homozygosity and linkage disequilibrium analysis for 14 patients from 11 NM families using 18 polymorphic markers. All of the patients from consanguineous NM families were found to be homozygous for six markers located within the region between markers D9S2178 and D9S1859. We also provided evidence for significant allelic associations between the NM region and five marker loci. Examination of the haplotype analysis identified a predominant ancestral haplotype comprising the associated alleles 199-160-154-109 (marker order: D9S2179-D9S2180-D9S2181-D9S1804), present in 60% of NM chromosomes and in 0% of parent chromosomes. On the basis of the data obtained in this study, the majority of NM chromosomes were derived from a single ancestral founder, and the NM gene is probably located within the 1.5-Mb region between markers D9S2178 and D9S1791.

Familial amyotrophic lateral sclerosis with a novel Leu126Ser mutation in the copper/zinc superoxide dismutase gene showing mild clinical features and lewy body-like hyaline inclusions.

BACKGROUND: Mutations in the SOD1 gene are responsible for approximately 25% of all familial amyotrophic lateral sclerosis (ALS) cases. However, the correlation between the clinical and pathological features and the various SOD1 gene mutations has not been well characterized. OBJECTIVES: To screen the SOD1 gene in search of potential mutations and to obtain clinical and pathological data for 2 Japanese families with ALS. DESIGN: Clinical histories and neurological findings, gross and microscopic pathological features, and DNA analysis of the SOD1 gene. RESULTS: The 2 families with ALS showed a novel missense mutation in the SOD1 gene, which was heterozygous for point mutation TTG to TCG, causing substitution of leucine for serine at codon 126 (Leu126Ser) in exon 5. Clinically, patients showed slower disease progression and lack of upper motor neuron signs. Neuropathologically, the autopsied patient showed the form of familial ALS with posterior column involvement, and the pontocerebellar tract and the dentate nuclei of the cerebellum were also involved. Furthermore, abundant Lewy body-like hyaline inclusions were observed in the affected motor and nonmotor neurons. CONCLUSIONS: Familial ALS with a novel Leu126Ser mutation in the SOD1 gene showed mild clinical features and lack of upper motor neuron signs. We believe that Leu126Ser might be associated with the clinical features and that the mutation site in the SOD1 gene and disease duration might be associated with the formation of Lewy body-like hyaline inclusions.

Photoactivated gene expression for cell fate mapping and cell manipulation.

A long-standing goal of developmental biologists is to create developmental fate maps by tracking individual cells through development. Another objective is to perturb the behavior of selected cells and follow the ensuing effects. To this end, we have developed a technique that allows for spatial and temporal control of gene expression in single cells or patches of cells using light to induce gene expression. This technique relies on "caging" the activity of the potent transcriptional activator GAL4VP16 with a photolabile compound, which can be removed with a brief exposure to long-wavelength ultraviolet (UV) light. The caged GAL4VP16 is injected into early-stage embryos, which are aged to the desired point in development, and the cell(s) of interest are irradiated with a brief pulse of long-wavelength UV light. This method has been used extensively in Drosophila, Xenopus, and Zebrafish embryos. The methods for purifying, caging, injection, and photoactivation of the GAL4VP16 protein, and methods for the visualization of marked cells are described in detail.

Mutations in the alpha-tubulin 67C gene specifically impair achiasmate segregation in Drosophila melanogaster.

Drosophila melanogaster oocytes heterozygous for mutations in the alpha-tubulin 67C gene (alphatub67C) display defects in centromere positioning during prometaphase of meiosis I. The centromeres do not migrate to the poleward edges of the chromatin mass, and the chromatin fails to stretch during spindle lengthening. These results suggest that the poleward forces acting at the kinetochore are compromised in the alphatub67C mutants. Genetic studies demonstrate that these mutations also strongly and specifically decrease the fidelity of achiasmate chromosome segregation. Proper centromere orientation, chromatin elongation, and faithful segregation can all be restored by a decrease in the amount of the Nod chromokinesin. These results suggest that the accurate segregation of achiasmate chromosomes requires the proper balancing of forces acting on the chromosomes during prometaphase.

Esophageal varices before and after endoscopic variceal ligation: evaluation using helical CT.

The purpose of this study was to demonstrate the utility of helical CT in assessing the therapeutic effects of endoscopic variceal ligation (EVL). Twenty-four patients with esophageal varices were examined. Helical scanning was initiated 60 s after intravenous injection (Iopamidol 300 mgI/ml, total 120 ml, 3 ml/s) was started. Esophageal varices were clearly depicted as high-density areas. Multiplanar reformation and 3D images demonstrated collateral circulation three-dimensionally. After EVL, mucosal high-density areas had diminished markedly, but collateral veins around the esophagus, and gastro- and/or spleno-renal shunts, were unchanged in all patients. Of 21 patients with collateral circulation, esophageal varices recurred endoscopically in 6 patients within 12 months. In 3 patients without collateral circulation, esophageal varices did not recur within 12 months. From these findings, we conclude that helical CT is a useful method for assessing the therapeutic effects of EVL.

Direct determination of bisphenol A and nonylphenol in river water by column-switching semi-microcolumn liquid chromatography/electrospray mass spectrometry

A rapid and sensitive analytical method based on column-switching semi-microcolumn high-performance liquid chromatography (HPLC) with electrospray mass spectrometry was developed for determining trace levels of bisphenol A (2,2-bis(4-hydroxyphenyl)propane) and nonylphenol (4-nonylphenol) in river water. An aliquot of sample solution was directly injected into the precolumn packed with Capcellpak MF-Ph for sample cleanup and enrichment. The compounds of interest were then transferred to a C-18 analytical column for main separation through a change in flow path by a programmed switching valve. Bisphenol A, nonylphenol, and interfering substances were satisfactorily separated with a simple gradient elution complete within 35 min. Detection of their deprotonated molecules was conducted in negative ion mode. A reduced flow rate (100 &mgr;L/min) optimized for the narrow bore column was found advantageous in obtaining a high degree of sensitivity during electrospray detection. The influence of carrier additives on sensitivity was also examined. This method produced detection limits of 0.5 ng/mL for bisphenol A and 10 ng/mL for nonylphenol (signal-to-noise ratio 3). Calibration curves were observed in the range of 2.5-50 ng/mL (r(2) = 0.999) for bisphenol A and 50-500 ng/mL (r(2) = 0.998) for nonylphenol. Recoveries of the compounds from spiked distilled water and river water were 99.7-138.5% with a relative standard deviation (RSD) ranging from 2.2-9.7%. Copyright 1999 John Wiley & Sons, Ltd.

Fate mapping of Drosophila embryonic mitotic domain 20 reveals that the larval visual system is derived from a subdomain of a few cells.

In an attempt to study the fates of cells in the dorsal head region of Drosophila embryos at gastrulation, we used the photoactivated gene expression system to mark small numbers of cells in selected mitotic domains. We found that mitotic domain 20, which is a cluster of approximately 30 cells on the dorsal posterior surface, gives rise to various ectodermal cell types in the head, including dorsal pouch epithelium, the optic lobe, and head sensory organs, including Bolwig's organ, the larval photoreceptor organ. We found that the optic lobe and larval photoreceptors share the same origin of a few adjacent cells near the center of mitotic domain 20, suggesting that within the mitotic domain, there is a subdomain from which the larval visual system is specified. In addition to the components of the larval visual system, this central region of mitotic domain 20 also generates a part of the eye-antennal disc placode; cells that gives rise to the adult visual system. We also observed that a significant amount of cell death occurred within this domain and used cell ablation experiments to determine the ability of the embryo to compensate for cell loss.

Accumulation of milky fluid: a late complication of cataract surgery.

We describe 3 patients who presented with an accumulation of homogeneous milky fluid in the capsular bag several years after continuous curvilinear capsulorhexis, phacoemulsification, and posterior chamber intraocular lens (IOL) implantation. In each case, the entire edge of the anterior capsule opening was tightly attached to the peripheral IOL optic. The milky fluid was present in the closed chamber between the IOL optic and the posterior capsule. The fluid was sampled in 2 patients, and its concentration of sodium hyaluronate was determined by high-performance liquid chromatography. The concentration of sodium hyaluronate resembled that in normal aqueous humor. In 1 case, the protein concentration was measured and found to be elevated. Electrophoresis showed that human serum albumin was the main protein constituent. While the outcome was favorable in all 3 patients, this delayed complication of cataract surgery merits further study to clarify its etiology and pathogenesis.

Localization of hyaluronan in pseudocapsule from total hip arthroplasty.

Hyaluronan is a large glycosaminoglycan present in normal synovial fluid imparting important viscoelastic properties for joint lubrication. In normal and noninflammatory conditions, hyaluronan has been localized to the lining layer of the synovial membrane, specifically synovial fibroblasts. Prosthetic joint fluid contains large amounts of hyaluronan, the source of which has not been determined. Pseudocapsules from patients who had total hip arthroplasty and were having revision surgery for nonloosened and nonseptic conditions were fixed in 10% acid formalin with 70% alcohol and stained for hyaluronic acid with biotinylated hyaluronic acid binding protein as a probe. Hyaluronan was localized strongly to the lining layer of the pseudocapsule, as in normal and osteoarthritic synovial membranes. The fibroblasts in the pseudocapsule of total hip arthroplasty may be responsible for the persistent production of hyaluronan in prosthetic joint fluid.

Migration of polyethylene particles around stable implants in an animal model.

The aim of this study was to test the hypothesis that a tight seal between bone and implant will eliminate the avenue of particle migration around stable implants. Three types of implants were used in rabbits (polished press-fit Ti-6Al-4V or plasma-sprayed hydroxyapatite [HA]-coated Ti-6Al-4V) or doughy stage polymethyl methacrylate (PMMA). Implants were placed in the condylar notch. Each animal received an intra-articular injection of high density polyethylene (PE) particles (10(8) in 0.4 mL; mean size 4.7 microns) at 4 and 6 weeks postoperatively. Eight weeks postoperatively, peri-implant tissues were examined for PE particles and osteolysis. In all cases, intracellular PE particles were seen at the bone-implant interface and within marrow. No osteolysis was observed. Bone apposition was determined by computerized image analysis. There was no significant difference in the percentage of bone apposition (+/- SD) among the three groups of implants: Ti-6Al-4V (68% +/- 19%), HA-coated Ti-6Al-4V (70% +/- 10%), and PMMA (59% +/- 12%). These results indicate that a polished Ti-6Al-4V surface is as effective as PMMA or HA coating in limiting migration of PE particles around stable osseointegrated implants in rabbits.

In vitro uptake and release of TI-201 and Tc-99m MIBI in cultured tumor cells and effect of anticancer drug.

201Tl is useful in the diagnosis of tumor malignancy determined by the grade of washout rate to normal tissue, especially in lung tumors and thyroid tumors. 99mTc-MIBI, a tracer of myocardial blood flow, is also a tumor tracer. We examined whether the growth of tumor cells is related to the uptake and release of these tracers in cultured tumor cells. Cultured tumor cells (HeLa cells and squamous cell carcinomas derived from human lung cancer) were incubated for 60 min with 10 kBq of either tracer for the kinetic study of cellular uptake. They were additionally incubated for 90 min with cold medium for the kinetic study of cellular release. These cells cultured with various concentrations of actinomycin D (ACD) or CDDP were used to examine the correlation between the cellular growth and kinetics of these tracers. The cellular release of 201Tl increased relative to the concentration of added ACD or CDDP in both cell types. In contrast, the cellular release of 99mTc-MIBI was not changed by the addition of ACD in HeLa cells. In conclusion, 201Tl showed a slower washout rate in high-growth tumor cells than in low-growth tumor cells; thus, it could act as an indicator of tumor malignancy by assessing its washout rate.

Cementless implant composition and femoral stress. A finite element analysis.

Proximal atrophy and thigh pain are recognized problems with some cementless femoral stems in total hip arthroplasty. It is thought that reduced femoral stress from alterations in load transfer caused by an intramedullary stem contributes to proximal femoral atrophy. An increase in flexural rigidity and bone stress near the stem tip is thought to contribute to thigh pain. A three-dimensional finite element analysis study was performed to calculate stresses in the proximal femur and bone near the stem tip before and after implantation of a collared, proximally coated, cementless femoral prosthesis. The influence of prosthetic material was examined by changing implant composition from cobalt chrome to titanium alloy and leaving all other parameters constant. Femoral stress was increased twofold immediately below the collar with the titanium implant compared with the cobalt chrome. However, the proximal femoral stress in the titanium implanted model was still 1/10 that in the corresponding region of the unimplanted femur model. At the stem tip, as much as a 30% reduction in femoral stress was seen with the titanium stem compared with the cobalt chrome. These findings suggest biomechanical evidence of an advantage for titanium as an implant material compared with cobalt chrome for cementless femoral stems.

Spontaneous repair of superficial defects in articular cartilage in a fetal lamb model.

A fetal lamb model was developed to investigate the capacity of fetal articular cartilage for repair after the creation of a superficial defect. Superficial defects, 100 micrometers deep, were made in the articular cartilage of the trochlear groove in the distal aspect of the femur in eighteen fetal lambs that were halfway through the 145-day gestational period; the contralateral limb was used as a sham control. The wounds were allowed to heal in utero for three, seven, fourteen, twenty-one, or twenty-eight days. Seven days after the injury, the defects were filled with a hypocellular matrix, which stained lightly with safranin O. At twenty-eight days, the staining of the matrix was similar to that of the sham controls and the chondrocyte density and the architectural arrangement of the cell layers had been restored. An inflammatory response was not elicited, and no fibrous scar tissue was observed.

Revision total hip arthroplasty with correctional femoral osteotomy in Paget's disease.

Varus alignment of the femoral component is associated with femoral component loosening in total hip arthroplasty performed for Paget's disease. Irregular and hemorrhagic bone, along with angular femoral deformity, was encountered during revision total hip arthroplasty in three pagetic patients. A diaphyseal femoral osteotomy facilitated cement removal and provided an opportunity for correction of the deformity. The step-cut configuration of the osteotomy provided intrinsic rotational stability of the femoral segments around a modular, long-stem cementless implant. Excellent clinical and radiographic results were achieved, but moderate blood loss and delayed healing of the osteotomy site were observed.