Systematic Review of Literature of Cemented Femoral Components: What Is the Durability at Minimum 20 Years Followup?

Background

Cemented femoral total hip arthroplasty may be one of the most successful surgical interventions of all time. However, although results are very encouraging over the early to mid-term followup, relatively few studies have analyzed the durability of these implants beyond 20 years followup. To evaluate the performance of contemporary implants, it is important to understand how previous implants perform at 20 or more years of followup; one way to do this is to aggregate the available data in the form of a systematic review.

Questions/purposes

(1) How durable is cemented femoral fixation in the long term (minimum 20-year followup) with respect to aseptic loosening? (2) Is the durability of cemented femoral fixation dependent on age of the patient? (3) Are the long-term results of the cemented femoral fixation dependent on any identifiable characteristics of the prosthesis such as surface finish?

Methods

A systematic review was performed to identify long-term studies of cemented femoral components. After application of inclusion and exclusion criteria to 1228 articles found with a search in PubMed and EMBASE, 17 studies with a minimum of 20-year followup on cemented femoral components were thoroughly analyzed in an attempt to answer the questions of this review. The quality of the studies reviewed was assessed with the Methodological Index for Nonrandomized Studies (MINORS) instrument. All studies were case series and cohort sizes ranged from 110 to 2000 hips for patients older than 50 years of age and 41 to 93 hips for patients younger than 50 years at the time of surgery.

Results

Among the six case series performed in patients older than 50 years of age, survivorship for aseptic loosening of the femoral component ranged from 86% to 98% at 20 years followup. There were no obvious differences for younger patients when analyzing the five studies in patients younger than age 50 years in which survivorship free from aseptic loosening for these studies ranged from 77% at 20 years in one study and 68% to 94% at 25 years in the other studies. Although data pooling could not be performed because of heterogeneity of the studies included here, it appeared that stems with a rougher surface finish did not perform as well as polished stems; survivorship of stems with rougher surface finishes varied between 86% and 87%, whereas those with smoother finishes ranged between 93.5% and 98% at 20 years.

Conclusions

Excellent long-term fixation in both older and younger patients can be obtained with cemented, polished femoral stems. These results provide material for comparison with procedures performed with newer cementing techniques and newer designs, both cemented and cementless, at this extended duration of followup.     

Contribution of permeability and sensitivity to inhibition of DNA synthesis in determining susceptibilities of Escherichia coli, Pseudomonas aeruginosa, and Alcaligenes faecalis to ciprofloxacin.

To examine the correlation between bacterial cell susceptibility to ciprofloxacin and the magnitude of uptake and cell target sensitivity, the relative contribution of ciprofloxacin accumulation in intact cells and its ability to inhibit DNA synthesis were investigated among strains of Escherichia coli, Pseudomonas aeruginosa, and Alcaligenes faecalis. Uptake studies of [14C]ciprofloxacin demonstrated diffusion kinetics for P. aeruginosa and E. coli. Ciprofloxacin was more readily removed from E. coli J53 and A. faecalis ATCC 19018 by washing than from P. aeruginosa PAO503. These results indicate that the process of cell accumulation is different for P. aeruginosa in that the drug is firmly bound at an extracellular site. Whatever the washing conditions, A. faecalis accumulated less drug than either of the other two bacteria. Magnesium chloride (10 mM) caused a substantial decrease of ciprofloxacin accumulated and an increase in the MIC, depending upon the nature of the medium. The addition of carbonyl cyanide m-chlorophenylhydrazone caused a variable increase in drug accumulated, depending on the medium and the bacterial strain. The concentration of ciprofloxacin required to obtain 50% inhibition (ID50) of DNA synthesis for P. aeruginosa PAO503 and A. faecalis ATCC 19018 did not correlate with their corresponding MICs but did for E. coli J53. Treatment with EDTA decreased the ID50 of ciprofloxacin for P. aeruginosa PAO503 and its gyrA derivative by 5- and 2-fold, respectively, and decreased the ID50 for E. coli JB5R, a strain with a known decrease in OmpF, by 1.4-fold but did not decrease the ID50 for the normally susceptible E. coli J53. The ID(50) for P. aeruginosa obtained after EDTA treatment or in ether-permeabilized cells was higher than that obtained for the other two strains. The protonophore carbonyl cyanide m-chlorophenylhydrazone prevented killing by low ciprofloxacin concentrtaions, but sodium azide did not. The latter compound did not enhance killing in association with inhibition of a previously described energy-dependent efflux of ciprofloxacin susceptibility being the susceptibility to inhibition of DNA synthesis in E. coli, poor premeability associated with the small pore size of A. faecalis, and a combination of low permeability and reduced susceptibility of DNA synthesis to inhibition for P. aeruginosa.     

Rejection sensitivity and multiple group memberships: The moderating role of an oxytocin receptor gene polymorphism

Rejection sensitivity is a cognitive-affective processing disposition that has been linked to interpersonal difficulties. In this regard, the neuropeptide hormone, oxytocin, is thought to underlie social cognitions and behaviors that promote social affiliation. A single nucleotide polymorphism (SNP) on the oxytocin receptor gene (OXTR), in which guanine (G) is substituted for adenine (A), has been associated with less support-seeking behaviors. In the current study, among 376 undergraduate students, it was shown that the relationship between rejection sensitivity and depressive symptoms was mediated by multiple group memberships. Furthermore, the relation between rejection sensitivity and group memberships was only evident among individuals possessing the A allele on the OXTR gene. These findings further support the psychosocial deficits characteristic of individuals possessing the OXTR polymorphism, which in turn is linked to poor mood.     

Action of 5-Hydroxytryptamine,Substance P,Thyrotropin Releasing Hormone and Clonidine on Spinal Neuron Excitability

Abstract

We investigated the influence of four substances on the excitability of lumbar motoneurons. These substances, three of which coexist in the same bulbospinal descending pathways that end, for the most part, around motoneurons (MNS), are: 5-hydroxytryptamine (5-HT), substance P (SP) and thyrotropin-releasing hormone (TRH). We also studied the effects of Clonidine, an alpha 2 noradrenergic (NA) agonist. This study was carried out in rats spinalized at T5 and treated three weeks earlier with 5–7 dihydroxytryptamine (5–7 DHT). Under these conditions, the following responses were observed: 5-HTP (5-HT precursor) intraperitoneally (I.P.), 5-HT intrathecally (I.T.), TRH (I.P. or I.T.) and substance P (I.T.) all elicited strong excitation of MNS as measured by integrated EMG of the hindlimb muscles; substance P reduced by almost half the response to 5-HTP given one hour and 24 hours later; TRH given acutely did not modify the response to 5-HTP, but given chronically for 21 days markedly increased the response to this substance. Clonidine by itself decreased the excitability of MNS and antagonized the excitatory effects of 5-HTP and TRH. In two separate pilot trials, cyproheptadine, a 5-HTP antagonist, decreased the manifestations of spasticity in a patient with a partial spinal lesion. It would appear that Clonidine may have potential use in the management of spasticity. (J Spinal Cord Med; 18:42–46)     

Newly generated neurons in the amygdala and adjoining cortex of adult primates

The subventricular zone remains mitotically active throughout life in rodents. Studies with tritiated thymidine, which is incorporated into the DNA of mitotic cells, have revealed that the rodent subventricular zone produces neuroblasts that migrate toward the olfactory bulb along the rostral migratory stream. A similar migratory stream has been documented in monkeys by using the thymidine analogue BrdUrd. The same approach showed that neurogenesis occurred in the dentate gyrus of adult primates, including humans. In the present study, experiments combining injections of BrdUrd and the dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindo-carbocyanine, with the immunostaining for molecular markers of neurogenesis (polysialylated neural cell adhesion molecule, beta-tubulin-III, collapsin response mediator protein-4, neuronal nuclear protein) in New World (Saimiri sciureus) and Old World (Macaca fascicularis) monkeys have revealed that new neurons are produced in the amygdala, piriform cortex, and adjoining inferior temporal cortex in adult primates. These newborn neurons expressed the antiapoptotic protein Bcl-2 and formed a more-or-less continuous pathway that extended from the tip of the temporal ventricular horn to the deep portion of the temporal lobe. The production of newborn neurons in the amygdala, piriform cortex, and inferior temporal cortex seems to parallel the continuing addition of neurons in the olfactory bulb. These two concomitant phenomena may ensure structural stability and functional plasticity to the primate olfactory system and temporal lobe.     

Stemming Resistance to HER-2 Targeted Therapy

Although the development of trastuzumab and lapatinib has improved the outlook for women with HER-2 positive breast cancer, resistance to HER-2 targeted therapy is a growing clinical dilemma. Recent evidence indicates that the HER-2 pathway may play an important role in the maintenance of cancer stem cells (CSCs). The success of HER-2 targeted therapies may, in part, be explained by their direct activity against HER-2 positive CSCs. Our understanding of the mechanisms involved in resistance to trastuzumab, including loss or blockade of the trastuzumab binding site, activation of alternative signaling pathways, and induction of epithelial–mesenchymal transition (EMT), suggests that CSCs may be at the root of resistance of HER-2 targeted therapy. A variety of novel HER-2 targeted approaches have demonstrated promising preliminary clinical activity. Future clinical trials should involve the integration of technologies to assess the impact of novel HER-2 targeted therapies on HER-2 positive CSCs.