Modeling electrochromic poly-dioxythiophene-containing materials through TDDFT.

A DFT/TDDFT model was developed to predict the chemical properties for three colored to nearly transmissive electrochromic polymers synthesized by the John Reynolds's group. Using a functional-basis set pairing of mPW1PBE/cc-PVDZ along with the conductor polarizable calculation model (CPCM), simulated neutral spectra showed a strong correlation to the experimental UV-Vis data where the largest absolute peak maximum difference was 14 nm. Frontier molecular orbitals, electronic transitions, and ground-state geometries of these systems were evaluated to provide further information about the oxidative process the polymers undergo. Here we report the first colorimetric model using this level of theory.

Verticillium dahliae Infects, Alters Plant Biomass, and Produces Inoculum on Rotation Crops.

Verticillium wilt, caused by Verticillium dahliae, reduces yields of potato and mint. Crop rotation is a potential management tactic for Verticillium wilt; however, the wide host range of V. dahliae may limit the effectiveness of this tactic. The hypothesis that rotation crops are infected by V. dahliae inoculum originating from potato and mint was tested by inoculation of mustards, grasses, and Austrian winter pea with eight isolates of V. dahliae. Inoculum density was estimated from plants and soil. Typical wilt symptoms were not observed in any rotation crop but plant biomass of some crops was reduced, not affected, or increased by infection of specific isolates. Each isolate was host-specific and infected a subset of the rotation crops tested but microsclerotia from at least one isolate were observed on each rotation crop. Some isolates were host-adapted and differentially altered plant biomass or produced differential amounts of inoculum on rotation crops like arugula and Austrian winter pea, which supported more inoculum of specific isolates than potato. Evidence of asymptomatic and symptomatic infection and differential inoculum formation of V. dahliae on rotation crops presented here will be useful in designing rotations for management of Verticillium wilt.

Targeting AKT/PKB to improve treatment outcomes for solid tumors.

The serine/threonine kinase AKT, also known as protein kinase B (PKB), is the major substrate to phosphoinositide 3-kinase (PI3K) and consists of three paralogs: AKT1 (PKBα), AKT2 (PKBß) and AKT3 (PKBγ). The PI3K/AKT pathway is normally activated by binding of ligands to membrane-bound receptor tyrosine kinases (RTKs) as well as downstream to G-protein coupled receptors and integrin-linked kinase. Through multiple downstream substrates, activated AKT controls a wide variety of cellular functions including cell proliferation, survival, metabolism, and angiogenesis in both normal and malignant cells. In human cancers, the PI3K/AKT pathway is most frequently hyperactivated due to mutations and/or overexpression of upstream components. Aberrant expression of RTKs, gain of function mutations in PIK3CA, RAS, PDPK1, and AKT itself, as well as loss of function mutation in AKT phosphatases are genetic lesions that confer hyperactivation of AKT. Activated AKT stimulates DNA repair, e.g. double strand break repair after radiotherapy. Likewise, AKT attenuates chemotherapy-induced apoptosis. These observations suggest that a crucial link exists between AKT and DNA damage. Thus, AKT could be a major predictive marker of conventional cancer therapy, molecularly targeted therapy, and immunotherapy for solid tumors. In this review, we summarize the current understanding by which activated AKT mediates resistance to cancer treatment modalities, i.e. radiotherapy, chemotherapy, and RTK targeted therapy. Next, the effect of AKT on response of tumor cells to RTK targeted strategies will be discussed. Finally, we will provide a brief summary on the clinical trials of AKT inhibitors in combination with radiochemotherapy, RTK targeted therapy, and immunotherapy.

Correction: Yes and Lyn play a role in nuclear translocation of the epidermal growth factor receptor.

In Figure 4C, it was identified that the Histone H3 and α-Tubulin purification control blots for YES and LYN overexpressing cells were duplicated. The original Histone H3 control blot was found and confirmed the published results, however, the α-Tubulin control blot was not found. This error was determined to not impact the scientific findings of this figure. The authors regret this error.

A comparison of two biomaterial carriers for osteogenic protein-1 (BMP-7) in an ovine critical defect model.

Critical size defects in ovine tibiae, stabilised with intramedullary interlocking nails, were used to assess whether the addition of carboxymethylcellulose to the standard osteogenic protein-1 (OP-1/BMP-7) implant would affect the implant's efficacy for bone regeneration. The biomaterial carriers were a 'putty' carrier of carboxymethylcellulose and bovine-derived type-I collagen (OPP) or the standard with collagen alone (OPC). These two treatments were also compared to "ungrafted" negative controls. Efficacy of regeneration was determined using radiological, biomechanical and histological evaluations after four months of healing. The defects, filled with OPP and OPC, demonstrated radiodense material spanning the defect after one month of healing, with radiographic evidence of recorticalisation and remodelling by two months. The OPP and OPC treatment groups had equivalent structural and material properties that were significantly greater than those in the ungrafted controls. The structural properties of the OPP- and OPC-treated limbs were equivalent to those of the contralateral untreated limb (p > 0.05), yet material properties were inferior (p < 0.05). Histopathology revealed no residual inflammatory response to the biomaterial carriers or OP-1. The OPP- and OPC-treated animals had 60% to 85% lamellar bone within the defect, and less than 25% of the regenerate was composed of fibrous tissue. The defects in the untreated control animals contained less than 40% lamellar bone and more than 60% was fibrous tissue, creating full cortical thickness defects. In our studies carboxymethylcellulose did not adversely affect the capacity of the standard OP-1 implant for regenerating bone.

Database resources of the National Center for Biotechnology Information.

In addition to maintaining the GenBank nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides data analysis and retrieval resources that operate on the data in GenBank and a variety of other biological data made available through NCBI's Web site. NCBI data retrieval resources include Entrez, PubMed, LocusLink and the Taxonomy Browser. Data analysis resources include BLAST, Electronic PCR, OrfFinder, RefSeq, UniGene, HomoloGene, Database of Single Nucleotide Polymorphisms (dbSNP), Human Genome Sequencing, Human MapViewer, GeneMap'99, Human-Mouse Homology Map, Cancer Chromosome Aberration Project (CCAP), Entrez Genomes, Clusters of Orthologous Groups (COGs) database, Retroviral Genotyping Tools, Cancer Genome Anatomy Project (CGAP), SAGEmap, Gene Expression Omnibus (GEO), Online Mendelian Inheri-tance in Man (OMIM), the Molecular Modeling Database (MMDB) and the Conserved Domain Database (CDD). Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of the resources can be accessed through the NCBI home page at: http://www.ncbi.nlm.nih. gov.

Protein kinase C-epsilon transgenic mice: a unique model for metastatic squamous cell carcinoma.

Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are the most common forms of human skin cancer. BCC is slow growing and mostly localized, whereas SCC metastasizes to the regional lymph nodes and subsequently to distal organs. In murine skin carcinogenesis models for SCC, the incidence of metastasis is very low. We report here that FVB/N transgenic mice, which overexpress (approximately 18-fold) epitope-tagged protein kinase C-epsilon (T7-PKCepsilon) protein in the epidermis provide a unique murine model system for highly malignant/metastatic SCC. Skin tumors were developed by the initiation-promotion protocol (initiation with 100 nmol 7,12-dimethyl-benz[a]anthracene; promotion with 5 nmol 12-O-tetradecanoylphorbol-13-acetate twice weekly). T7-PKCepsilon transgenic mice showed 92% suppression of papilloma development compared with wild-type littermates after 23 weeks of tumor promotion. However, within 15-20 weeks of 12-O-tetradecanoylphorbol-13-acetate promotion, 40% of T7-PKCepsilon mice developed at least one carcinoma compared with 7% of the wild-type mice. All carcinomas from T7-PKCepsilon mice appeared without prior papilloma formation. Interestingly, 7,12-dimethyl-benz[a]anthracene alone resulted in the development of squamous cell carcinomas in 22% of T7-PKCepsilon mice, whereas wild-type littermates developed no tumors. Histopathological analysis of tumors from multiple T7-PKCepsilon mice revealed moderately differentiated SCC invading the dermal region with neoplasia appearing to originate and invade from the hair follicle. Carcinomas of T7-PKCepsilon mice rapidly metastasized to regional lymph nodes within 3 weeks of appearance. In wild-type mice, the grade of the invading tumors, originating from interfollicular epidermis, was pathologically categorized as well-differentiated SCC and remained localized to the dermis. The T7-PKCepsilon transgenic mice may provide a rapid and unique in vivo model to investigate metastatic SCC.

Protein kinase C epsilon signals ultraviolet light-induced cutaneous damage and development of squamous cell carcinoma possibly through Induction of specific cytokines in a paracrine mechanism.

Protein kinase C (PKC), a family of phospholipid-dependent serine/threonine kinases, is not only the major intracellular receptor for the mouse skin tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) but also is activated by a variety of stress factors including ultraviolet radiation (UVR). PKCepsilon is among six isoforms (alpha, delta, epsilon, eta, mu and zeta) expressed in the mouse skin. To determine the in vivo functional specificity of PKCepsilon in mouse skin carcinogenesis, we generated PKCepsilon transgenic mouse (FVB/N) lines 224 and 215 that overexpress PKCepsilon protein approximately 8- and 18-fold, respectively, over endogenous levels in the basal epidermal cells and cells of the hair follicle. PKCepsilon transgenic mice were observed to be highly sensitive to the development of papilloma-independent metastatic squamous cell carcinoma (mSCC) elicited either by repeated exposure to UVR or by the 7,12-Dimethylbenzanthracene-TPA tumor promotion protocol. The development of squamous cell carcinoma (SCC) appears to be linked to the PKCepsilon-mediated induction of cytokine tumor necrosis factor-alpha(TNFalpha). Immunohistochemical analysis for the expression of PKCepsilon in the SCC of PKCepsilon transgenic mice revealed that PKCepsilon was not expressed in the tumor itself; however, the uninvolved tissue surrounding the SCC exhibited intense PKCepsilon expression. Also, human SCC, similar to mouse SCC, did not express PKCepsilon in the tumor, whereas the surrounding uninvolved epidermis revealed strong PKCepsilon expression. These findings in both the PKCepsilon mouse model and human SCC indicate that overexpression of PKCepsilon in epidermis may lead to a microenvironment, which is suitable for enhancing the development of mSCC by a paracrine mechanism involving specific cytokines including TNFalpha.

The short- and long-term effects of methotrexate on the rat skeleton.

Both clinical and laboratory studies have shown that the chemotherapy drug, Methotrexate (MTX), has adverse short-term effects on bone. There are no studies that demonstrate the long-term response of bone to MTX. The purpose of this study was to determine the short- and long-term effects of MTX on bone volume, turnover, mineralization and strength. Three-month-old Sprague-Dawley rats were randomly assigned to a control (CTL) or MTX group and were given either daily MTX or saline injections for two separate 5-day courses (5 on/9 off/5 on). Fluorochrome compounds were injected prior to killing to label actively mineralizing bone surfaces. One CTL and MTX group were killed at 30, 80 and 170 days after treatment. Both femurs and tibiae were harvested for cancellous and cortical bone histomorphometry and biomechanical testing (torsion). Standard cancellous and cortical histomorphometric parameters were measured from undecalcified, methyl-methacrylate-embedded sections from the right proximal tibia and tibial and femoral diaphyses. The contralateral femur and tibia were torsionally loaded to failure and standard mechanical parameters were measured. All bone responses were statistically analyzed using a two-way ANOVA followed by Duncan's multiple comparison procedure (significance: p = 0.05). Cancellous bone volume was significantly lower in the MTX-treated group at 80 and 170 days. Cancellous mineralizing surface and longitudinal bone growth were significantly depressed at all time points yet mineral apposition rate was only depressed at the 170-day point. Cancellous osteoclast surface was increased at all time points for the MTX-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging and photoperiod regulate glutamic acid decarboxylase(67) messenger RNA expression.

Aging and short photoperiod exposure both induce similar long-term changes in circadian rhythms, including alterations in the timing and the amplitude of rhythms. Furthermore, these chronic conditions affect the function of the circadian pacemaker in the suprachiasmatic nuclei (SCN) by altering rhythmic expression of neuropeptide messenger RNAs (mRNAs). Because GABA modulates SCN neuronal activity, and GABAergic neurons innervate peptidergic neurons in the SCN, the present study investigated whether photoperiod or aging affect the expression of mRNA for GAD(67), the enzyme responsible for regulating the tonic levels of GABA. As a control for regional specificity, the reticular thalamic nucleus (RTN) was also examined. In situ hybridization for GAD(67) mRNA was performed on brain sections derived from Siberian hamsters exposed to a long day or a short day photoperiod for 15 days, and on brain sections from young (3-4 months old) and old (12-17 months old) Syrian hamsters exposed to a long photoperiod. The results showed that photoperiod and aging have different effects on GAD(67) mRNA expression. Exposure to short day photoperiod significantly increased GAD(67) mRNA expression in both the SCN and RTN of Siberian hamsters, while aging significantly decreased GAD(67) mRNA expression in the RTN of Syrian hamsters but had no effect on GAD(67) mRNA expression in the SCN. These findings suggest that modulation of GAD(67) mRNA expression in the SCN is associated with photoperiodic regulation of neuropeptide mRNA expression, but is not a common mechanism for chronic regulation of circadian rhythms. Also, GAD(67) mRNA expression in the RTN is differentially affected by photoperiod and aging.

Comparison of the effects of aging on 5-HT7 and 5-HT1A receptors in discrete regions of the circadian timing system in hamsters.

The circadian timekeeping system exhibits many functional changes with aging, including a loss of sensitivity to time cues such as systemic injections of the serotonergic agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). In order to elucidate the neurochemical mechanisms responsible for this age-related loss of sensitivity of the circadian pacemaker to serotonin agonists, the present study used quantitative autoradiography to determine whether aging decreases serotonin receptor populations in male Syrian hamsters. Four neuroanatomical regions that regulate circadian timekeeping were studied (the suprachiasmatic nuclei [SCN], the lateral geniculate nuclei [LGN], and the median raphe nucleus [MRN] and dorsal raphe nucleus [DRN]). The specific binding of [3H]8-OH-DPAT to serotonin7 (5-HT7) and serotonin1A (5-HT1A) receptors was investigated by competitive inhibition with ritanserin and pindolol, respectively. The results showed that the SCN, IGL, MRN, and DRN of the male Syrian hamster exhibited specific binding of [3H]8-OH-DPAT to both the 5-HT7 and 5-HT1A receptors, and that the latter receptor subtype is more abundant in all of these regions. At 17-19 months of age, a 50% decrease in 5-HT7 receptors was found in the DRN but not in any other regions. No significant age-related changes in 5-HT1A receptors were observed in any regions examined. The finding that a marked decrease in 5-HT7 receptors occurs in the DRN at the age previously characterized by loss of sensitivity to 8-OH-DPAT suggests that this region and this receptor subtype play important roles in 8-OH-DPAT induction of circadian phase shifts in vivo and that they constitute an important locus of aging in the circadian timing system.

Aging regulates 5-HT(1B) receptors and serotonin reuptake sites in the SCN.

Middle age is associated with changes in circadian rhythms (e.g., alterations in the timing of the circadian wheel running rhythm) which resemble changes induced by selective destruction of the serotonergic input to the suprachiasmatic nucleus (SCN), the principal mammalian circadian pacemaker. We hypothesized that serotonergic neurotransmission in the SCN is decreased in middle-aged hamsters, as compared to young adults. This hypothesis was tested indirectly by investigating the effect of aging on two markers of serotonin neurotransmission, 5-HT(1B) receptors and serotonin reuptake sites, which are regulated by serotonin. Previous studies have shown that experimentally induced decreases in serotonergic neurotransmission increase 5-HT(1B) receptors but decrease serotonin reuptake sites. Quantitative autoradiography was conducted using [125I]iodocyanopindolol ([125I]ICYP) and [3H]paroxetine, selective radioligands for the 5-HT(1B) receptors and the serotonin reuptake sites, respectively. Consistent with the hypothesis, specific ([125I]ICYP binding was significantly elevated in the SCN of middle-aged hamsters, as compared to young hamsters. The results also showed that serotonin reuptake sites in the SCN were significantly increased in both middle-aged and old hamsters, as compared to young controls. This result could not have been caused by decreased serotonin release. Alternatively, increased serotonin reuptake, which would reduce serotonin levels in the synaptic cleft, may cause or contribute to the increase in 5-HT(1B) receptor binding in the SCN in middle aged animals. These results show that the SCN exhibits changes in serotonergic function during middle age, which has been characterized by changes in the expression of circadian rhythms. Because these changes occur during middle age, they probably reflect the aging process, rather than senescence or disease.

Assessment of resorbable bioactive material for grafting of critical-size cancellous defects.

Bioactive glasses form a surface apatite layer in vivo that enhances the formation and attachment of bone. Sol-gel Bioglass graft material provides greater nanoscale porosity than bioactive glass (on the order of 50-200 A), greater particle surface area, and improved resorbability, while maintaining bioactivity. This study histologically and biomechanically evaluated, in a rabbit model, bone formed within critical-sized distal femoral cancellous bone defects filled with 45S5 Bioglass particulates, 77S sol-gel Bioglass, or 58S sol-gel Bioglass and compared the bone in these defects with normal, intact, untreated cancellous bone and with unfilled defects at 4, 8, and 12 weeks. All grafted defects had more bone within the area than did unfilled controls (p < 0.05). The percentage of bone within the defect was significantly greater for the 45S5 material than for the 58S or 77S material at 4 and 8 weeks (p < 0.05), yet by 12 weeks equivalent amounts of bone were observed for all materials. By 12 weeks, all grafted defects were equivalent to the normal untreated bone. The resorption of 77S and 58S particles was significantly greater than that of 45S5 particles (p < 0.05). Mechanically, the grafted defects had compressive stiffness equivalent to that of normal bone at 4 and 8 weeks. At 12 weeks, 45S5-grafted defects had significantly greater stiffness (p < 0.05). At 8 and 12 weeks, all grafted defects had significantly greater stiffness than unfilled control defects (p < 0.05). In general, the 45S5-filled defects exhibited greater early bone ingrowth than did those filled with 58S or 77S. However, by 12 weeks, the bone ingrowth in each defect was equivalent to each other and to normal bone. The 58S and 77S materials resorbed faster than the 45S5 materials. Mechanically, the compressive characteristics of all grafted defects were equivalent or greater than those of normal bone at all time points.

Effects of running on the torsional strength, morphometry, and bone mass of the rat skeleton.

Intensity and duration effects of weight-bearing exercise on the rat skeleton were investigated. Eighty-four 3-month-old female Sprague-Dawley rats were assigned to control and nine exercise groups. Exercised rats were run on a treadmill for either 30, 60, or 90 min.d-1 at low (Vo2max approximately 55%), medium (VO2max approximately 65%), or high (VO2max approximately 75%) intensity 4 d.wk-1 for 10 wk. Rat femurs, tibias, and vertebrae were harvested for torsional mechanical tests, bone density assessment, and morphometry. Our results indicate exercise has a significant effect (P < 0.05) on the femoral mechanical response (energy absorbed and twist angle), tibial morphometry (cortical bone area and thickness), and tibial and vertebral bone density measurements but had no effect (P > 0.05) on bone strength when compared with control values. Higher intensity exercise decreased tibial and femoral torque (P < 0.05). Long duration exercise increased tibial and femoral stiffness and decreased twist angle and energy absorbed (P < 0.05). These results indicate bone adapts to its loading environment by increasing bone mineral density, increasing cortical bone area, increasing stiffness, decreasing energy absorbed, and decreasing twist angle. High-intensity exercise decreased the maximum force the bone could withstand, whereas long duration exercise made the bone more brittle.

Functional assessment for prediction of lifting capacity.

OBJECTIVE: This study investigated the ability to predict maximal functional lifting capacity from peak isometric lumbar extension torque and submaximal lifting mechanics. METHODS: Peak isometric lumbar extension torques were measured on 26 healthy men and women, ages 18 to 39 years. In addition, their lifting mechanics were evaluated while they lifted a submaximal load. Each subject's maximal lifting capacity (kg) then was predicted from the peak torque and submaximal kinetic analysis using a linear regression model. RESULTS: Mean values for the predicted and actual maximum weight the subjects lifted were not significantly different (50.3 +/- 15.6 kg and 48.5 +/- 17.0 kg, respectively, P > or = 0.05). The correlation between predicted and criterion values was high (r = 0.96), and the total error of the prediction was 5.1 kg, which represented 10.5% of the actual maximum value. CONCLUSIONS: This multi-faceted functional assessment model involving biomechanical analysis of a submaximal lift and maximal isometric lumbar extension strength accurately predicted a subject's maximum functional lifting capacity.

Stress fractures of the femoral shaft in athletes--more common than expected. A new clinical test.

Athletes from 20 Division I AA collegiate varsity sports and 1 club sport were followed carefully for the development of stress fractures during the 1990 to 1991 and the 1991 to 1992 academic years. During this period, among 914 athletes, 34 stress fractures were sustained. Seven of these, or 20.6%, were of the femoral shaft. This represents a much higher incidence than previously observed in athletes. A new clinical test is described that significantly aids in the early diagnosis and follow-up treatment of femoral shaft stress fractures.

Stress fractures of the sacrum. An atypical cause of low back pain in the female athlete.

Low back pain is a common finding in an athletically active premenopausal female population. We describe an unusual cause of persistent low back/sacroiliac pain: a fatigue-type sacral stress fracture. Plain radiographs, bone scans, computed tomography, and magnetic resonance imaging studies were obtained in the female athletes to determine the nature of the pathologic abnormality. The most significant risk factor for fatigue-type sacral stress fractures was an increase in impact activity due to a more vigorous exercise program. Potential risk factors such as abnormal menstrual history, dietary deficiencies, and low bone mineral density were examined. The clinical course was protracted, with an average 6.6 months of prolonged low back pain before resolution of symptoms. Sacral fatigue-type stress fractures did not preclude the athletes from returning to their previous level of participation once healing had occurred.

Reliability of passive wrist flexion and extension goniometric measurements: a multicenter study.

BACKGROUND AND PURPOSE: The purpose of this study was twofold: (1) to determine whether passive wrist flexion and extension goniometric measurements using ulnar alignment, radial alignment, and volar/dorsal alignment were similar or dissimilar and (2) to examine which of these three techniques had the greatest intratester and intertester reliability. SUBJECTS: One hundred forty patients (141 wrists) were measured. The testers were 32 therapists from eight different hand/upper-extremity clinical sites around the United States. METHODS: Randomly paired testers measured passive wrist flexion and extension. The intraclass correlation coefficient (ICC) was used as an estimate of agreement for both intratherapist (model 3.1) and intertherapist (model 2.1) reliability. RESULTS: Six of the eight clinics showed significant differences among the various goniometric techniques. Flexion intratherapist mean ICCs for the radial, ulnar, and dorsal alignment techniques were .86, .87, and .92, respectively. Extension intratherapist mean ICCs were .80, .80, and .84 for the three techniques. Intertherapist flexion mean ICCs were .88, .89, and .93 for the radial, ulnar, and volar alignment techniques, respectively. Extension intertherapist mean ICCs were .80, .80, and .84 for the three techniques. The standard error of measurement was also used to quantify reliability, with the volar/dorsal alignment technique consistently producing less error than the ulnar and radial alignment techniques. The generalizability theory statistical model was utilized to identify the sources of error. The patient contributed to variance the most, although inherent error within the study, diagnostic category, therapeutic approach, and goniometric technique also contributed. CONCLUSION AND DISCUSSION: The overall results indicated there were differences among the three goniometric techniques. The volar/dorsal alignment technique is the goniometric technique of choice, as it consistently had the greatest reliability.

Biomechanical comparison of intramedullary and percutaneous pin fixation for proximal humeral fracture fixation.

OBJECTIVES: The purpose of this study was to investigate the mechanical strength and durability of intramedullary nailing (IM) and percutaneous pinning (PP) for fixation of three-part proximal humeral fractures using a cadaveric model. DESIGN: Three-part surgical neck fractures were created in paired embalmed cadaveric humeri. Fractures were fixed with IM and PP fixation. The fixation stiffness and durability was assessed under cyclic rotational loading (infraspinatus) ramping from 0.1 to 1.25 Newton-meters for 10,000 cycles. The specimen were then torsionally loaded to failure. SETTING: Mechanical testing was performed using a servohydraulic test system (MTS, Minneapolis, MN, U.S.A.). INTERVENTION: PP fixations were accomplished using standard multiplane techniques. IM fixation was attained using an 11.0-millimeter-diameter curved rod interlocked proximally with three splayed 5.0-millimeter cancellous screws and distally with three 3.5-millimeter cortical screws. MAIN OUTCOME MEASUREMENTS: During cyclic loading the reconstruction stiffness, angular migration, and angular displacement per cycle were measured and compared between fixation methods. The ultimate torque at failure, absolute angular migration, and reconstruction stiffness during failure were recorded and compared between fixation methods during destructive testing. RESULTS: The intramedullary device had greater stiffness and less angular displacement of fragments during cyclic loading. When loading the reconstructions to failure, the intramedullary device proved to have greater failure torques, stiffness, energy absorbed, and angular displacement before failure. CONCLUSIONS: This biomechanical study showed that the IM device provided a stronger, more stable, and durable fixation option than did PP fixation for large-fragment multipart proximal humeral fractures with minimal comminution.

Biomechanical evaluation of the dynamic hip screw with two- and four-hole side plates.

OBJECTIVES: To determine the biomechanical strength and stiffness of a dynamic hip screw (DHS; Synthes USA, Paoli, PA, U.S.A.) with a two-hole side-plate as compared with a four-hole side-plate design for the reconstruction of unstable three-part intertrochanteric fractures. DESIGN: Eight matched pairs of embalmed human femurs were tested in two modes: (a) 2,000 cycles of simulated physiologic loading; (b) test to failure. SETTING: Laboratory. Simulated single leg stance using a simulated pelvic loading mechanism with abductor loading. Strain and displacement sensors were used to measure fragment shear and distraction and surface strain in the proximal side plate. SPECIMENS: Eight pairs of skeletonized embalmed cadaveric specimens were selected on the basis of femoral neck angle and absence of old fracture, anatomic anomaly, or pathology. INTERVENTION: The specimens were divided into two groups: (a) left femurs received the two-hole side-plate design; (b) right femurs received the four-hole side-plate design. All fractures were reconstructed by the same surgeon using the manufacturer's instructions. MAIN OUTCOME MEASUREMENTS: Implant placement was verified by radiographic measurement of tip-to-apex distance. In cyclic testing, the amount of femoral neck fragment migration in both distraction and shear was quantified. Strain magnitude in the side plate was measured in both cyclic and failure testing. The peak load withstood by the reconstruction was quantified in the failure test. RESULTS AND CONCLUSIONS: Peak load in the failure test was not found to be statistically different between the two-hole and four-hole designs. In cyclic testing, the two-hole configuration exhibited statistically smaller fragment migration in both shear and distraction than the four-hole design (p < 0.05). The strain magnitude in the side plate was not statistically different in the cyclic or failure tests. The femurs with a greater neck angle failed by crushing of the bone in the neck. The femurs with a lesser neck angle failed due to bending of the hardware. The results of this investigation revealed that the two-hole DHS is biomechanically as stable as the four-hole DHS in cyclic and failure loads under the conditions tested. These results, in concert with clinical experience, can be used to support the use of the two-hole DHS for the reconstruction of intertrochanteric fractures without a diaphyseal extension.