Analysis of an early intervention tibial component for medial osteoarthritis.

Tibial component loosening is an important failure mode in unicompartmental knee arthroplasty (UKA) which may be due to the 6-8 mm of bone resection required. To address component loosening and fixation, a new early intervention (EI) design is proposed which reverses the traditional material scheme between femoral and tibial components. The EI design consists of a plastic inlay for the distal femur and a thin metal plate for the proximal tibia. With this reversed materials scheme, the EI design requires minimal tibial bone resection compared with traditional UKA. This study investigated, by means of finite element (FE) simulations, the advantages of a thin metal tibial component compared with traditional UKA tibial components, such as an all-plastic inlay or a metal-backed onlay. We hypothesized that an EI tibial component would produce comparable stress, strain, and strain energy density (SED) characteristics to an intact knee and more favorable values than UKA components, due primarily to the preservation of dense cancellous bone near the surface. Indeed, FE results showed that stresses in the supporting bone for an EI design were close to intact, while stresses, strains, and strain energy densities were reduced compared with an all-plastic UKA component. Analyzed parameters were similar for an EI and a metal-backed onlay, but the EI component had the advantage of minimal resection of the stiffest bone.

Cytokine gene expression in epidermis with biological effects following injection of naked DNA.

The epidermis is readily accessible for genetic manipulation and is easily monitored. Using pig skin because it is very similar to human skin morphologically, we have developed a method to transiently express biologically active factors in epidermis. Following direct injection of naked plasmid DNA into skin, DNA is taken up and transiently expressed at high levels by epidermal keratinocytes. Injection of interleukin-8 plasmid DNA into skin results in the appropriate biological response of neutrophil recruitment, demonstrating functional utility. In addition to this model's therapeutic uses, the biological effects of structural gene products on the epidermis could also be studied in vivo.

The Gerbich blood group system: a review.

Antigens in the Gebrich blood group system are expressed on glycophorin C (GPC) and glycophorin D (GPD), which are both encoded by a single gene, GYPC. The GYPC gene is located on the long arm of chromosome 2, and Gebrich antigens are inherited as autosomal dominant traits. There are 11 antigens in the Gebrich blood group system, six of high prevalence (Ge2, Ge3, Ge4, GEPL [Ge10*], GEAT [Ge11*], GETI [Ge12*]) and five of low prevalence (Wb [Ge5], Ls(a) [Ge6], An(a) [Ge7], Dh(a) [Ge8], GEIS [Ge9]). GPC and GPD interact with protein 4.1R, contributing stability to RBC membrane. Reduced levels of GPC and GPD are associated with hereditary elliptocytosis, and Gebrich antigens act as receptors for the malarial parasite Plasmodium falciparum. Anti-Ge2 and anti-Ge3 have caused hemolytic transfusion reactions, and anti-Ge3 has produced hemolytic disease of the fetus and newborn (HDFN).

Future directions in knee replacement.

The use of artificial joints for the treatment of osteoarthritis is expected to expand considerably over the next decade. While newer technologies can offer yet further improvements in total knee systems, implementation will be strongly affected by the need to satisfy apparently competing requirements. Patients expect quicker rehabilitation, improved performance, and lifelong durability; on the other hand, economic constraints require a reduction in cost for each procedure, as well as early intervention and preventative measures, while there is increased pressure from health care systems to use evidence-based medicine as the standard of choice for implants and techniques. The success of a knee replacement depends on the design itself, the surgical technique, the rehabilitation, and, not least, the patient. The major goal of the implant design can be redefined as a restoration of normal knee mechanics, whether by maximum preservation of tissues, or by guiding surfaces that replace their function. Surgical technique needs to be less invasive but achieve optimal patient-specific alignment and soft tissue balancing. Rehabilitation procedures must achieve the expectations of realistic patients. Testing and evaluation methods need to be upgraded for enhanced predictability. This paper discusses current trends and future possibilities to address this expansive scope of design criteria.

Alloanti-c in a c-positive, JAL-positive patient.

BACKGROUND AND OBJECTIVES: In the Rh blood group system, partial D, C, and e antigens are well-known, but a partial c antigen resulting in the production of alloanti-c in a c+ individual is rare. One example of an alloanti-c in a c+ person was an anti-Rh26, which can appear as anti-c, and another was an alloanti-c in a c+ person with a presumed R(1)r phenotype. The finding of an apparent alloanti-c in a transfused c+ patient initiated this investigation. MATERIALS AND METHODS: Haemagglutination tests, DNA extraction, polymerase chain reaction (PCR)-based assays (PCR-restriction fragment length polymorphism, allele-specific PCR), reticulocyte mRNA extraction, reverse transcriptase (RT)-PCR and sequencing were performed by standard procedures. RESULTS: Plasma from a 64-year-old African American woman with a wound infection following a mastectomy contained anti-E, anti-S, anti-K, anti-Fy(a) and anti-Jk(b), reacting by the indirect antiglobulin test. In addition, the patient's plasma gave reactions that were consistent with an anti-c, while her pre-transfusion red blood cells typed c+ with some anti-c reagents. These results are consistent with a partial c antigen. The patient's red blood cells also typed V+(W)VS- and JAL+. Analyses of DNA and Rh-transcripts from this patient showed the presence of the following genes: RHD*D, RHD*DAU0, RHCE*Ce and RHCE*ce(S)(340). CONCLUSION: The nucleotide 340C>T change in RHCE exon 3 (predicted to encode 114Trp) of the RHCE*ce(S)(340) allele is associated with a JAL+ phenotype and the altered expression of the c, V and VS antigens. This alteration in the c antigen allowed the patient to make an alloanti-c. This case reveals that the RHCE*ce(S)(340) allele encodes a partial c antigen.

Feasibility of single-use 3D-printed instruments for total knee arthroplasty.

AIMS: This aim of this study was to assess the feasibility of designing and introducing generic 3D-printed instrumentation for routine use in total knee arthroplasty. MATERIALS AND METHODS: Instruments were designed to take advantage of 3D-printing technology, particularly ensuring that all parts were pre-assembled, to theoretically reduce the time and skill required during surgery. Concerning functionality, ranges of resection angle and distance were restricted within a safe zone, while accommodating either mechanical or anatomical alignment goals. To identify the most suitable biocompatible materials, typical instrument shapes and mating parts, such as dovetails and screws, were designed and produced. RESULTS: Before and after steam sterilization, dimensional analysis showed that acrylonitrile butadiene styrene could not withstand the temperatures without dimensional changes. Oscillating saw tests with slotted cutting blocks produced debris, fractures, or further dimensional changes in the shape of Nylon-12 and polymethylmethacrylate (MED610), but polyetherimide ULTEM 1010 was least affected. CONCLUSION: The study showed that 3D-printed instrumentation was technically feasible and had some advantages. However, other factors, such as whether all procedural steps can be accomplished with a set of 3D-printed instruments, the logistics of delivery, and the economic aspects, require further study. Cite this article: Bone Joint J 2019;101-B(7 Supple C):115-120.

Expression of naked DNA in human, pig, and mouse skin.

The insertion and expression of genes in the epidermis may have a variety of therapeutic uses, including the treatment of skin diseases. Here we show that when both human skin organ cultures and human skin grafts on immunocompromised mice are injected with naked DNA, the DNA is taken-up and genes are expressed in the epidermis in a manner similar to both pig skin injected in vivo and injected pig skin organ cultures. In contrast, DNA injected into mouse skin is expressed not just in the epidermis, but also in the dermis and underlying fat and muscle tissue, and is expressed at lower levels. These findings suggest that genes can be expressed in human skin, after injection of naked DNA, and indicate that pig skin is an appropriate model for the study of DNA uptake and gene expression in human skin. The organ cultures of human and pig skin may be useful in understanding how naked DNA is internalized and expressed after in vivo injections. Additionally, skin obtained from patients with skin disease may be studied as skin grafts and organ cultures to help optimize genetic approaches for the treatment of skin diseases prior to clinical trials, by determining if the injected gene can provide a therapeutic benefit.

A confusion in antibody identification: anti-D production after anti-hrB.

It is well known that certain combinations of alloantibodies are frequently found together. Patients with sickle cell disease (SCD) are mostly ofAfrican ancestry,and they may make anti-hrB. A transfusion of hrB- blood is often achieved by using e- (R2R2) RBCs; it is generally believed that hrB- patients readily make anti-E or a"broad-spectrum" anti-Rh34 (-HrB). We describe two multiply transfused D+ patients with SCD and a history of anti-hrB who subsequently produced anti- D. This raises the question whether anti-hrB together with anti-D is a more common antibody combination than anti-hrB with anti-E or anti-Rh34.

The use of hydroxyapatite-coated CAD-CAM femoral components in adolescents and young adults with inflammatory polyarthropathy: ten-year results.

Between June 1991 and January 1995, 42 hydroxyapatite-coated CAD-CAM femoral components were inserted in 25 patients with inflammatory polyarthropathy, 21 of whom had juvenile idiopathic arthritis. Their mean age was 21 years (11 to 35). All the patients were reviewed clinically and radiologically at one, three and five years. At the final review at a mean of 11.2 years (8 to 13) 37 hips in 23 patients were available for assessment. A total of four femoral components (9.5%) had failed, of which two were radiologically loose and two were revised. The four failed components were in patients aged 16 years or less at the time of surgery. Hydroxyapatite-coated customized femoral components give excellent medium- to long-term results in skeletally-mature young adults with inflammatory polyarthropathy. Patients aged less than 16 years at the time of surgery have a risk of 28.5% of failure of the femoral component at approximately ten years.

Measurements of constraint of total knee replacement.

Measurement of the constraint of total knee components in a test machine provides an objective method of describing the laxity and stability characteristics of the implant itself, independent of the knee joint into which it would be implanted. A special fixture was designed and fitted to a Bionix multi-channel loading machine. The test consisted of applying a compressive load, applying a cyclic AP force or internal-external torque, and measuring all of the displacements and rotations. Three different commonly-used TKR's showed widely different constraint characteristics. In the cyclic AP test, along with the cyclic AP displacement, displacements and rotations occurred in the other directions. This indicated that all degrees of freedom should be free to move, otherwise anomalous results would be obtained. The paper concludes with recommendations for standardized constraint tests.

Viral interference during simultaneous transduction with two independent helper-free retroviral vectors.

The ability to stably transduce a single cell with two independent retroviral vectors would have distinct advantages for gene therapy. We determined that cells can be transduced with two distinct retroviral vectors and have quantitated transduction efficiencies in cells infected sequentially and simultaneously. Two amphotropic, helper virus-free, retroviral vectors, a murine Moloney sarcoma virus-based vector containing the nuclear beta-galactosidase and neomycin resistance genes (MMSVn beta-gal/neoR) and a Harvey virus-derived vector containing the human multidrug resistance gene (HaMDR) were introduced into NIH-3T3 cells, pig keratinocytes, and primary pig fibroblasts simultaneously and sequentially. Analytical flow cytometry was utilized to determine retroviral transduction efficiency by assessing the percentage of cells transduced by either one or both retroviruses, in the absence of selection. Simultaneous retroviral transductions were infrequent events. In addition, transduction of previously infected cells (sequential transductions) occurred at lower than expected frequencies. Our data suggest that there is quantifiable viral interference in sequential retroviral transductions. This interference occurs by a mechanism that appears to be independent of the amphotropic retroviral receptor. Thus, such dual transductions will likely require in vitro selection or the use of a single retrovirus which contains both desired genes on the same genome.

Genetic immunization with glycoprotein 63 cDNA results in a helper T cell type 1 immune response and protection in a murine model of leishmaniasis.

Genetic immunization is a promising gene therapy approach for the prevention and treatment of infectious disease. Plasmid DNA expressing genes of pathogens is directly introduced into host cells and specific cell-mediated and/or humoral immune responses are elicited against the encoded protein. Leishmaniasis is a significant world-wide health problem for which no vaccine exists. In susceptible animals, such as BALB/c mice, protection from leishmaniasis requires induction of a Thl immune response. In this study, cell-mediated immunity to Leishmania major (L. major) was induced by injecting BALB/c mice intradermally with plasmid DNA expressing the conserved L. major cell surface glycoprotein gp63 (gp63-pcDNA-3). CD4 T lymphocytes from gp63-pcDNA-3-immunized mice proliferated and produced IFN-gamma (but not IL-4) when stimulated in vitro with freeze-thawed parasites, consistent with a Th1 immune response. In contrast, lymphocyte proliferation in animals immunized with freeze-thawed parasites was associated with IL-4 (but not IFN-gamma) production, suggesting a nonprotective Th2 response. Challenge studies revealed that gp63-pcDNA-3 vaccination protected 30% of susceptible mice (21 of 70) from Leishmania infection while neither gp63 protein (0 of 20) nor freeze-thawed parasite vaccines (0 of 50) were efficacious. Dendritic cells derived from skin of gp63-pcDNA-3-injected mice also immunized naive recipients and protected them from leishmaniasis. We conclude that gp63-pcDNA-3 genetic vaccination results in a CD4-dependent Th1 immune response that correlates with protection from disease, and suggest that skin-derived dendritic cells are involved in priming this response.

Regulation of the glucose transporter in developing rat brain.

We have found a complex alteration in the expression of the glucose transporter protein and mRNA in developing rat brain tissue. Before birth (gestational days 19-20), the rat brain glucose transporter was comprised of a diffuse protein doublet of approximately 43,000 and 50,000 mol wt (Mr) by Western blot analysis. Immediately after birth (1-2 days), the total amount of immunoreactive glucose transporter decreased approximately 5-fold, primarily due to a loss of the higher (50,000) Mr component with a relatively smaller decrease in the 43,000 Mr band. Subsequently, the amount of the 43,000 Mr band progressively increased from days 5 to 60 and the 50,000 Mr band increased from days 15 to 60. By 60 days postdelivery, the relative amounts of the glucose transporter protein were similar to those on the 19th gestational day. N-Glycanase treatment of the developing rat brain membranes demonstrated that the regulation of the two different Mr weight glucose transporter species occurred as a result of differential glycosylation. In contrast to the Western blot analysis, [3H] cytochalasin-B binding studies demonstrated no significant developmental alteration in the total amount of glucose transporter protein in rat brain tissue. However, consistent with the Western blots, Northern blot analysis using rat brain transporter cDNA revealed a dramatic decrease in the content of the glucose transporter mRNA immediately subsequent to birth, followed by a gradual increase back to the prenatal levels. These data suggest that the rat brain-type glucose transporter is developmentally regulated, but may be associated with the compensatory expression of another unidentified glucose transporter protein in newborn rats.

Functional differences in insulin receptors in rat adipocyte and human placenta membranes.

Incubation of human placenta membranes with low concentrations (0.1-0.2 mM) of dithiothreitol (DTT) increased insulin binding approximately 1.4-fold, while 10 mM DTT completely inhibited insulin binding. In contrast, treatment of rat adipocyte membranes with 0.5-2.0 mM DTT increased tracer insulin binding 3- to 6-fold, while higher levels of DTT (10 mM) also fully inhibited insulin binding. Scatchard analysis of insulin binding revealed that DTT treatment of adipocyte membranes resulted in an increase in both the high and low affinity dissociation constants. Purification of adipocyte insulin receptors by wheat germ agglutinin-Sepharose chromatography, followed by insulin-agarose affinity chromatography, resulted in loss of DTT stimulation of insulin binding. Comparison of insulin receptors purified from rat adipocytes or human placenta membranes revealed no significant differences in the DTT sensitivities of insulin binding or protein kinase activities. These data suggest that the functional properties of the rat adipocyte insulin receptor are modified by its membrane environment compared to those of insulin receptors in placenta membranes or purified insulin receptors in detergent solution.

Attachment and proliferation of osteoblasts and fibroblasts on biomaterials for orthopaedic use.

Using a variety of cell types, cell attachment and growth was studied on prospective (polyethersulphone (PES) and polyetheretherketone) and currently used (titanium 318 alloy, cobalt chrome molybdenum alloy and ultra-high molecular weight polyethylene (UHMWPE)) orthopaedic biomaterials. Proliferation of fibroblasts and osteoblasts was measured using incorporation of tritiated thymidine into total DNA. Attachment of cells was assessed by indirect immunofluorescent labelling of vinculin, a component of the cell's focal adhesion plaque. The degree of cell attachment was quantified on the materials by determining the mean number of adhesion plaques and using an image analysis system to determine the mean total area of plaques per cell. Fibroblasts and osteoblasts responded differently to the materials tested. When grown on PES surfaces, rat tail fibroblasts synthesized significantly greater amounts of DNA than cells on all other surfaces, whilst fibroblasts on UHMWPE synthesized significantly less DNA than cells on all other materials. Interestingly, there was no significant difference between the amounts of DNA synthesized by osteoblasts grown on the various materials. Determination of the number of vinculin adhesion plaques per cell and the mean total area of the plaques per cell showed that the attachment of fibroblasts to UHMWPE was significantly reduced compared with other materials. In contrast there was no significant difference in the adhesion of osteoblasts to different materials. Scanning electron microscope (SEM) observations of cells on the materials correlated with the morphometric data. Cells with the greatest number and area of adhesion plaques were well spread and flattened whilst those with the least number of adhesion plaques were more rounded and less spread.

Osseo-mechanical induction of extra-cortical plates with reference to their surface properties and geometric designs.

The purpose of this investigation was to determine which geometric and surface properties encouraged optimal ingrowth and bonding of bone to an extra-cortical plate. Forty-eight titanium extra-cortical plates were attached onto the left and right femora of adult rabbits. The plates were of six different designs and the osseoconductive effects of four surfaces were examined. A roughened titanium surface, a plasma sprayed HA coating of low crystallinity (57%) and a solution precipitated calcium phosphate coating were compared with a plasma sprayed crystalline hydroxyapatite coating (crystallinity 85%). Thin sections were prepared by grinding and polishing. Bone formation and the interface around the plates were investigated histologically and computer and morphometric analyses were used to quantify new bone formation, bone apposition onto the plate, bone porosity and the condition of the HA coating. The study found that a hydroxyapatite coating (with the exception of the solution precipitated coating) had significantly greater interfacial contact with bone when compared to a roughened titanium surface, and that significantly more bone attached to a crystalline HA coating compared with the HA coating of lower crystallinity although significantly more bone formed in the vicinity of the lower crystalline HA coating. Differences in the bony reaction induced by the various geometric designs were evident and the optimal plate design requires either holes or slots along its length as this encouraged bone ingrowth into the plate.

The current status of total knee replacement.

Total knee replacement has come of age, and long-term results are much better than those for total hip replacement. The designs of the late 1980s have addressed function, mobility, wear, and long-term survival for the young and active. Conventional, cemented knee arthroplasty is highly successful and well represented by the state of the art in the Kinemax total knee replacement prosthesis. This design also has the capability of treating the postseptic knee, the knee that requires extensive bone grafting, and, experimentally, the young, the active, or the overweight patient.

Rudimentary meningocele presenting with a scalp hair tuft. Report of two cases.

BACKGROUND: Rudimentary meningoceles represent a developmental anomaly in which meningothelial elements are found in the skin. The majority of rudimentary meningoceles occur on the scalp over the occiput or along cranial suture lines. They are usually recognized at birth and present as a pink papule or nodule or an area of alopecia. OBSERVATIONS: We present two patients who presented with a scalp hair tuft at birth over a rudimentary meningocele. This finding has not been previously reported. CONCLUSIONS: Rudimentary meningoceles are uncommon developmental anomalies that are of clinical importance due to the occasional presence of connection to the central nervous system. Due to this potential for central nervous system connection, any midline lesion in an infant, including midline hair tufts, deserves careful preoperative evaluation including imaging studies.

Tazarotene cream for the treatment of facial photodamage: a multicenter, investigator-masked, randomized, vehicle-controlled, parallel comparison of 0.01%, 0.025%, 0.05%, and 0.1% tazarotene creams with 0.05% tretinoin emollient cream applied once daily for 24 weeks.

OBJECTIVE: To assess the safety and efficacy of 4 concentrations of tazarotene cream in the treatment of facial photodamage. DESIGN: Prospective weekly multicenter, investigator-masked, randomized, parallel-group study. SETTING: University hospitals and clinical research centers. PATIENTS: Three hundred forty-nine subjects with facial photodamage. INTERVENTION: Daily topical application of tazarotene cream (0.01%, 0.025%, 0.05%, and 0.1%) compared with its vehicle and with 0.05% tretinoin emollient cream. RESULTS: Tazarotene cream and tretinoin cream significantly improved mottled hyperpigmentation and fine wrinkles. At week 24, treatment success rates based on global responses were 67% (39 of 58 subjects) with 0.1% tazarotene, 52% (30 of 58 subjects) with 0.05% tazarotene, 36% (21 of 58 subjects) with 0.025% tazarotene, 41% (24 of 59 subjects) with 0.01% tazarotene, 55% (32 of 58 subjects) with 0.05% tretinoin, and 22% (13 of 58 subjects) with vehicle. Local adverse events, although more frequent with tazarotene at higher concentrations, were generally mild to moderate. CONCLUSIONS: Tazarotene in a cream formulation is safe and is associated with positive changes in the treatment of photodamaged facial skin.

A comparison of cortical strain after cemented and press-fit proximal and distal femoral replacement.

Proximal and distal femoral replacements with intramedullary stems are usually cemented in place but frequently show severe bone remodeling changes in the long term, which can contribute to a loosening process. The remodeling is likely to be associated with stress and strain distribution. This study compared the strain patterns, particularly the maximum principal strains, between cemented and press-fit components in five cadaveric femurs by using a photoelastic coating technique. The specimens were loaded with 2,000 N in the sequences of intact femur and press-fit and cemented stems. On the medial side of the bone for proximal femoral replacements, the strain values for the press-fit stems on the proximal, middle, and distal regions were 73 +/- 11%, 78 +/- 15%, and 80 +/- 15% of normal, respectively, but for the cemented stems they were 53 +/- 15%, 57 +/- 19%, and 60 +/- 20%. The differences were statistically significant (p less than 0.05). On the lateral side, the overall strain values for the press-fit stem were higher than those for the cemented stem, but the differences were not statistically significant (p greater than 0.05). On the medial side of the distal femoral replacement, the strain values for the press-fit stems in the proximal and middle regions were significantly closer to normal than for the cemented stems. Because the press-fit femoral stems (both the proximal and distal replacement) transferred closer to normal strains than the cemented stems, less adverse bone remodeling may be expected, which could be reflected in increased longevity.