Unstable intertrochanteric versus displaced femoral neck fractures treated with cementless bipolar hemiarthroplasty in elderly patients; a comparison of 80 matched patients.

BACKGROUND: While hemiarthroplasty (HA) is considered the treatment of choice for displaced femoral neck (FN) fractures in elderly patients, HA has been partly performed as an alternative treatment option for unstable intertrochanteric (IT) fractures. However, there is a paucity of data regarding the risk and availability of HA for unstable IT fractures compared to HA for displaced FN fractures in elderly patients. Therefore, we performed this case-control study to determine whether HA for unstable IT fractures provides clinical results and survival comparable to HA for displaced FN fractures in elderly patients. HYPOTHESIS: HA for unstable IT fractures in elderly patients provides clinical results and 1-year survival comparable to HA for displaced FN fractures in the same aging group. MATERIALS AND METHODS: We identified 80 patients aged 75years or older, who underwent cementless bipolar HA for unstable IT fracture (AO/OTA type 31-A2.2/3 and A3.3). Their clinical results and 1-year survival were compared to the matched control group of 80 patients with displaced FN fractures (Garden type 3 and 4) treated with the same procedure. Perioperative results, postoperative complications, and 1-year survival were investigated between the two groups. Functional outcome was assessed by walking status and Harris hip score (HHS) 6months after surgery. RESULTS: Operating time was significantly longer in the IT group than the FN group (97.3min [50 to 255] vs. 79.3min [40 to 175], P=0.016). However, the two groups did not significantly differ regarding perioperative results, such as total blood loss, transfusion, intraoperative fracture, length of hospital stay, and postoperative complication. No statistically significant differences in walking status and HHS were observed between the groups. No significant difference in cumulative survival was observed between the two groups (P=0.836), with a 1-year survival rate of 80% (95% confidence interval [CI], 71.8 to 87.5) in the IT group and 82% (95% CI, 73.1 to 89.4) in the FN group. CONCLUSION: HA for unstable IT fractures in elderly patients showed clinical results and 1-year survival comparable to HA as the treatment of choice for displaced FN fractures in the same aging group. LEVEL OF EVIDENCE: Level III, case-control study.

Management of traumatic labral tear in acetabular fractures with posterior wall component.

BACKGROUND: Posterior labral tear is frequently encountered in acetabular fractures with posterior wall component (AFPWC). However, there has been very little information in the literature on the type and management of traumatic labral tears in AFPWC. HYPOTHESIS: Traumatic labral tear is a constant intracapsular injury in AFPWC and can be repaired using adequate methods according to its type and size. MATERIALS AND METHODS: A retrospective study of 14 patients (mean age 38 years [16-58]) who underwent open surgery for AFPWC was conducted using prospectively collected data. The types of posterior labral tear were investigated at intraoperative examination through the ruptured joint capsule or its extension, and were concomitantly managed. Surgical outcomes were clinically assessed using Merle d'Aubigné (PMA) score and Visual Analog Scale (VAS), and radiologically evaluated at final follow-up. RESULTS: Posterior labral tears were present in all 14 patients. The types of labral tear were osseous avulsion and posterior root avulsion tear (n=9), longitudinal peripheral tear and posterior root avulsion tear (n=2), longitudinal peripheral tear (n=2), and osseous avulsion tear (n=1). All unstable labra in 12 patients (86%) were repaired. All avulsion tears of the posterior root were repaired using a suture anchor, longitudinal peripheral tears using suture fixation or/and suture anchors, and osseous avulsion tears using a spring plate. The mean PMA score and VAS were 16.4 (14-18) and 1.7 (0-3) at final follow-up, respectively. The radiologic grades at last follow-up were good or excellent in all patients. DISCUSSION: All AFPWC in this study consistently revealed posterior labral tear. Posterior root avulsion tears accompanied with osseous avulsion was the most common type. Torn labra should be repaired as much as possible if unstable, considering the important functions of a normal labrum; fixation using a suture anchor may be useful for an avulsion tear of the posterior root. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Tribological property of the cobalt-chromium femoral head with different regions of wear in total hip arthroplasty.

The tribological properties of engineering and biological materials have been investigated at microscale levels through the calculation of the surface roughness and frictional coefficient using atomic force microscopy (AFM). Although a number of previous studies have reported the frictional coefficients of diverse bearing materials in total hip arthroplasty (THA), the relationship between the surface roughness and frictional coefficient of bearing materials of THA have not been reported, and furthermore, the tribological properties for different wear regions of a cobalt-chromium (Co-Cr) femoral head have not been well identified. Therefore, the objective of this study is to investigate the relationships between the surface roughness, frictional coefficient, and hardness for both the main-wear and the least-wear regions of a Co-Cr femoral head 10 years after THA. The average Vickers hardness of the Co-Cr femoral head was 380.7 +/- 11.3 HV. With the scanned area of 25 microm x 25 microm through AFM, the frictional coefficients of the main-wear and the least-wear regions were 0.229 +/- 0.054 and 0.243 +/- 0.059, respectively, and showed no statistical differences between these two regions (p = 0.449). However, differences in the surface roughness (Rq) between the main-wear region (Rq = 96.5 +/- 26.2 nm) and the least-wear region (Rq = 17.7 +/- 4.2 nm) were statistically significant (p < 0.0001). The results of the current study suggest that the frictional property of the Co-Cr femoral head is not significantly correlated with its surface roughness, and also provide guidelines for improving the surface characteristics of metallic implant materials.

Impregnation of vancomycin, gentamicin, and cefotaxime in a cement spacer for two-stage cementless reconstruction in infected total hip arthroplasty.

Twenty-two patients with infected total hip arthroplasty were treated with 2-stage arthroplasty, using a cement spacer impregnated with a combination of 3 thermostable antibiotics (vancomycin, gentamicin, and cefotaxime). Initially, implants were removed, and a spacer was inserted. Six to 12 weeks later, the spacer was removed, and the patients underwent reconstruction using cementless components. The patients were followed for an average of 41 months. One patient had a recurrence of infection and was treated with resection arthroplasty. The remaining 21 patients (95%) had no evidence of infection at the final follow-up. We recommend using the combination of these 3 antibiotics in the cement spacer for 2-stage reconstruction in infected hip arthroplasty when the causative organism is not identified in the culture of preoperative aspiration.

Roles of phosphatidylinositol 3-kinase and Rac in the nuclear signaling by tumor necrosis factor-alpha in rat-2 fibroblasts.

We investigated the extent to which phosphatidylinositol 3-kinase (PI 3-kinase) and Rac, a member of the Rho family of small GTPases, are involved in the signaling cascade triggered by tumor necrosis factor (TNF)-alpha leading to activation of c-fos serum response element (SRE) and c-Jun amino-terminal kinase (JNK) in Rat-2 fibroblasts. Inhibition of PI 3-kinase by LY294002 or wortmannin, two specific PI 3-kinase antagonists, or co-transfection with a dominant negative mutant of PI 3-kinase dose-dependently blocked stimulation of c-fos SRE by TNF-alpha. Similarly, LY294002 significantly diminished TNF-alpha-induced activation of JNK, suggesting that nuclear signaling triggered by TNF-alpha is dependent on PI 3-kinase-mediated activation of both c-fos SRE and JNK. We also found nuclear signaling by TNF-alpha to be Rac-dependent, as demonstrated by the inhibitory effect of transient co-transfection with a dominant negative Rac mutant, RacN17. Our findings suggest that Rac is situated downstream of PI 3-kinase in the TNF-alpha signaling pathway to the nucleus, and we conclude that PI 3-kinase and Rac each plays a pivotal role in the nuclear signaling cascade triggered by TNF-alpha.

The polycystic kidney disease 1 gene product mediates protein kinase C alpha-dependent and c-Jun N-terminal kinase-dependent activation of the transcription factor AP-1.

Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disorder that accounts for 8-10% of end stage renal disease. PKD1, one of two recently isolated ADPKD gene products, has been implicated in cell-cell and cell-matrix interactions. However, the signaling pathway of PKD1 remains undefined. We found that the C-terminal 226 amino acids of PKD1 transactivate an AP-1 promoter construct in human embryonic kidney cells (293T). PKD1-induced transcription is specific for AP-1; promoter constructs containing cAMP response element-binding protein, c-Fos, c-Myc, or NFkappaB-binding sites are unaffected by PKD1. In vitro kinase assays revealed that PKD1 triggers the activation of c-Jun N-terminal kinase (JNK), but not of mitogen-activated protein kinases p38 or p44. Dominant-negative Rac-1 and Cdc42 mutations abrogated PKD1-mediated JNK and AP-1 activation, suggesting a critical role for small GTP-binding proteins in PKD1-mediated signaling. Several protein kinase C (PKC) inhibitors decreased PKD1-mediated AP-1 activation. Conversely, expression of the C-terminal domain of PKD1 increased PKC activity in 293T cells. A dominant-negative PKC alpha, but not a dominant-negative PKC beta or delta, abrogated PKD1-mediated AP-1 activation. These findings indicate that small GTP-binding proteins and PKC alpha mediate PKD1-induced JNK/AP-1 activation, together comprising a signaling cascade that may regulate renal tubulogenesis.

L-alpha-aminoadipate inhibits kynurenate synthesis in rat brain hippocampus and tissue culture.

Intracerebral administration of L-alpha-aminoadipic acid (L-AAA) at 500 mg/kg body weight to rats caused a complex behavioral change with sporadic wet-dog shakes. Animals developed severe limbic seizures between 1 and 6 h after L-AAA injection, characterized by generalized convulsions. Twenty days after L-AAA injection kynurenine aminotransferase (KAT) activity measured in hippocampal brain tissue slices prepared with a McIlwain chopper at 30 microns showed a significant 43% decrease. Subcutaneous injection of kynurenine at 500 mg/kg showed a 63% increase in KAT activity twenty days later. This increase was offset by a concomitant administration of 500 mg/kg L-AAA stereotaxically on day one. In astrocyte culture kynurenic acid synthesis is inhibited by L-AAA and L-pipecolic acid. The possible involvement of kynurenic acid in the modulation of neuronal degeneration is discussed.

Association of HLA-DPB1*0301 with IDDM in Mexican-Americans.

Susceptibility to IDDM has been associated with specific alleles at the HLA class II loci in a variety of human populations. Previous studies among Mexican-Americans, a group ancestrally derived from Native Americans and Hispanic whites, showed that the DR4 haplotypes (DRB1*0405-DQB1*0302 and DRB1*0402-DQB1*0302) and the DR3 haplotype (DRB1*0301-DQB1*0201) were increased among patients and suggested a role for both DR and DQ alleles in susceptibility and resistance. Based on the analysis of 42 Mexican-American IDDM families and ethnically matched control subjects by polymerase chain reaction/sequence-specific oligonucleotide probe typing, we report an association of IDDM with the DPB1 allele, *0301 (relative risk = 6.6; P = 0.0012) in this population. The analysis of linkage disequilibrium patterns in this population indicates that the observed increased frequency in DPB1*0301 among patients cannot be attributed simply to linkage disequilibrium with high-risk DR-DQ haplotypes. These data suggest that in addition to alleles at the DRB1 and DQB1 loci, polymorphism at the DPB1 locus may also influence IDDM risk.

Nonconsolidated polyethylene particles and oxidation in Charnley acetabular cups.

Nonconsolidated particles of ultra high molecular weight polyethylene are believed to be defects that adversely can affect the wear performance of total joint prostheses. The present study was done to determine the number, size, and distribution of these particles and to determine if their presence correlated with wear performance, as well as with other clinical and implant parameters. Forty retrieved and 7 new, never-implanted acetabular components were examined using light microscopy on thin cross sections. Particles were found in 92% of retrieved components and in all the new components. Particles in the retrieved components were either randomly distributed (32 components) or banded (with particles localized in regions approximately 1 mm below the outer surface of the component). No correlations were found between the number or area of particles and the wear performance or any of the clinical or implant variables. The presence of particles in the new implants was found to correlate with the length of time since the components had been radiation sterilized. For retrieved components, the density (and, therefore, the level of oxidative degradation) was high in the areas of banded particles. For new components, the density was higher the longer the time since sterilization. Nonconsolidated polyethylene particles are prevalent in total replacements but their source and cause are unknown. The results of this study show that they do not appear to affect or correlate with the length of implantation of acetabular cups. However, they still may be expected to adversely affect performance in cases where large numbers of particles are banded together near articulating surfaces of high stress environments such as found in the knee.

Requirement for protein kinase C activation in basic fibroblast growth factor-induced human endothelial cell proliferation.

The intracellular signaling mechanisms that mediate basic fibroblast growth factor (bFGF)-induced angiogenesis have not been fully identified. In particular, whether activation of the intracellular enzyme protein kinase C (PKC) is necessary or sufficient for bFGF-induced mitogenesis of human endothelial cells is not clear. Accordingly, the effect of bFGF stimulation on the Ca2+ increase and PKC activity of normal human endothelial cells (HEC) was studied, as was the effect of inhibition of PKC and the distribution of PKC isoenzymes in these cells. The addition of bFGF to cultured HEC increased overall PKC activity in the absence of an increase in intracellular Ca2+ and markedly stimulated their proliferation, as did the addition of PKC-activating phorbol esters. bFGF-induced proliferation was prevented by the PKC inhibitors chelerythrine and H-7 and by downregulation of PKC after prolonged incubation with phorbol esters. In contrast, these inhibitors did not prevent HEC proliferation induced by epidermal growth factor. Because of the failure of bFGF to increase Ca2+, we determined whether bFGF-induced proliferation could be mediated by novel or atypical PKC isoenzymes (which are not regulated by Ca2+). Investigation of the isoenzyme distribution of confluent and subconfluent HEC by immunoblotting, Northern transfer analysis, and polymerase chain reaction of reverse-transcribed RNA revealed the presence of several novel and atypical isoenzymes (PKC-delta, -eta, -theta, and -zeta) as well as small amounts of the conventional (Ca(2+)-regulated) isoenzymes PKC-alpha and -beta. Activation of PKC by bFGF, in the absence of an increase in intracellular Ca2+, suggests that one or more of these Ca(2+)-independent PKC isoenzymes are both necessary and sufficient for HEC proliferation after bFGF.

PCR/oligonucleotide probe typing of HLA class II alleles in a Filipino population reveals an unusual distribution of HLA haplotypes.

We have analyzed the distribution of HLA class II alleles and haplotypes in a Filipino population by PCR amplification of the DRB1, DQB1, and DPB1 second-exon sequences from buccal swabs obtained from 124 family members and 53 unrelated individuals. The amplified DNA was typed by using nonradioactive sequence-specific oligonucleotide probes. Twenty-two different DRB1 alleles, including the novel Filipino *1105, and 46 different DRB1/DQB1 haplotypes, including the unusual DRB1*0405-DQB1*0503, were identified. An unusually high frequency (f = .383) of DPB1*0101, a rare allele in other Asian populations, was also observed. In addition, an unusual distribution of DRB1 alleles and haplotypes was seen in this population, with DR2 (f = .415) and DRB1*1502-DQB1*0502 (f = .233) present at high frequencies. This distribution of DRB1 alleles differs from the typical HLA population distribution, in which the allele frequencies are more evenly balanced. The distribution of HLA class II alleles and haplotypes in this Filipino population is different from that of other Asian and Pacific groups: of those populations studied to date; the Indonesian population is the most similar. DRB1*1502-DQB1*0502 was in strong linkage disequilibrium (D' = .41) with DPB1*0101 (f = .126, for the extended haplotype), which is consistent with selection for this DR, DQ, DP haplotype being responsible for the high frequency of these three class II alleles in this population.

Molecular cloning and expression of a cDNA encoding a novel isoenzyme of protein kinase C (nPKC). A new member of the nPKC family expressed in skeletal muscle, megakaryoblastic cells, and platelets.

At least seven bacteriophage lambda clones encoding structurally related but unique polypeptides with PKC activity have been isolated from mammalian brain, epidermis, and lung cDNA libraries. The possibility that additional isoenzymes are expressed in human blood platelets or megakaryoblastoid human erythroleukemia cells was examined by polymerase chain reaction amplification of reverse transcribed RNA employing oligonucleotide primers corresponding to conserved peptide sequences. cDNAs encoding a novel PKC-related sequence, designated PKC-theta, and four (alpha, beta, delta, and eta) previously identified isoenzymes were isolated from reverse transcribed total RNA of human erythroleukemia cells and platelets. PKC-theta lacks a conserved region (C2) that is present in the calcium-dependent isoenzymes and therefore belongs to the group of novel, or nPKC, isoenzymes. Significantly increased [3H] phorbol 12,13-dibutyrate binding and cytoskeleton-associated calcium-independent PKC activity were found in COS cells expressing the transfected cDNA. Northern transfer analysis of mRNA from various human tissues revealed high level expression of PKC-theta in skeletal muscle, lung, and brain, and minimal expression in cardiac muscle, placenta, and liver. These findings extend the PKC family and suggest a novel approach to the study of diversity within this pathway of intracellular signal transduction.

Effects of protease inhibitors on c-myc expression in normal and transformed C3H 10T1/2 cell lines.

In the present study, the effect of protease inhibitors on c-myc expression in normal and transformed C3H 10T1/2 cells was examined. Steady-state c-myc RNA levels were reduced in normal proliferating C3H 10T1/2 cells grown in medium containing antipain, leupeptin, and Bowman Birk inhibitor (BBI). These protease inhibitors have been shown previously to suppress transformation yields in carcinogen-exposed cells. A lesser reduction in c-myc RNA levels was observed when cells were grown in the presence of protease inhibitors that do not suppress carcinogenesis and when transformed C3H 10T1/2 cell populations were grown in the presence of the anticarcinogenic protease inhibitors. Studies to determine the effects of antipain on the stability of the c-myc message and on c-myc transcription rates were also performed. The half-life of the c-myc message increased from 10 to 40 min when cells were grown in antipain; cycloheximide further stabilized the c-myc message. Interestingly, nuclear run-off experiments showed that antipain had no effect on c-myc transcription rates. These data suggest that proteases may be involved in the regulation of c-myc RNA expression in normal C3H 10T1/2 cells, possibly by a posttranscriptional mechanism.

Cell cycle progression of C3H 10T1/2 and 3T3 cells in the absence of an increase in c-myc RNA levels.

Normally, when confluent cells are stimulated to divide, they show a transient increase in c-myc RNA levels (1-5). This has led many investigators to believe that the rise in c-myc RNA is causally related to the control and regulation of cell proliferation. However, we report here that the rise in c-myc RNA levels is not observed in stimulated cycling C3H 10T1/2 and 3T3 cells that have been grown to confluence in the presence of the protease inhibitor antipain. Cells continue to progress from the G0/G1 phase to S phase of the cell cycle in the absence of an increase in c-myc RNA; the kinetics of [3H]thymidine incorporation after serum stimulation are comparable to those observed in cells in which c-myc RNA levels rise after serum stimulation. Our observations are of significance because they suggest a dissociation between the transient rise of c-myc RNA which occurs before DNA synthesis and the events that initiate DNA synthesis in quiescent fibroblasts; c-myc may not play as central a role in stimulating noncycling, quiescent cells to progress through the cell cycle, as has been generally assumed.

Cytotoxic, cell cycle, and chromosomal effects of methylxanthines in human tumor cells treated with alkylating agents.

Human tumor cells, like rodent cells, are sensitive to effects of methylxanthines (MEX) on lethality, cell cycle delays, and chromosome aberrations after DNA damage by anticancer drugs. Enhanced cytotoxicity of alkylating agents was observed when T24 human bladder tumor cells in culture were exposed to nontoxic concentrations of MEX such as caffeine or pentoxifylline. Tumor cell lethality was increased up to 10-fold by either caffeine or pentoxifylline (1 mM) present during the first cell cycle (16-24 h) after exposure to nitrogen mustard (HN2) or thiotepa. Cycloheximide, a protein synthesis inhibitor, abolished the enhanced lethality produced by MEX. In these synchronized human tumor cells further kinetic studies revealed that HN2 (0.5 microM X 1 h) delayed transit through S phase by about 1-2 h, and this delay was prevented by MEX. After completion of S phase, HN2-treated cells were delayed 3-6 h in G2, and MEX also prevented this delay, leading to mitoses at the rate of controls. Chromosome analysis of these mitotic cells revealed dramatic increases in aberrations induced by alkylator + MEX combinations. The greatest number of aberrations was seen in HN2-treated cells exposed briefly to MEX in late S-G2. In contrast, no increased chromosome damage was seen in cells exposed to MEX in mid-S phase. Taken together, our results are consistent with the model that MEX enhance lethality of alkylator-treated human tumor cells by preventing delays in cell cycle transit through G2, leading to chromosome aberrations which are lethal. G2 delays in human tumor cells may provide time for repair processes that are critical for survival after sublethal DNA damage by HN2 or other anticancer alkylating agents.