A systematic review and meta-analysis of complications following the posterior and lateral surgical approaches to total hip arthroplasty

IntroductionTotal hip arthroplasty is one of the most commonly performed orthopaedic procedures. Despite this, medical evidence to inform the choice of surgical approach is lacking. Currently in the UK, the two most frequently performed approaches to the hip are the posterior and the direct lateral.MethodsThis systematic review was performed according to Cochrane guidelines following an extensive search for prospective controlled trials published in any language before January 2014. Of the 728 records identified from searches, 6 prospective studies (including 3 randomised controlled trials) involving 517 participants provided data towards this review.FindingsCompared with the lateral approach, the posterior approach conferred a significant reduction in the risk of Trendelenburg gait (odds ratio [OR]: 0.31, p=0.0002) and stem malposition (OR: 0.24, p=0.02), and a non-significant reduction in dislocation (OR: 0.37, p=0.16) and heterotopic ossification (OR: 0.41, p=0.13). Neither approach conferred a functional advantage. We draw attention to the paucity of evidence and the need for a further randomised trial.     

Characterization and quantification of dynamic eccentric regurgitation of the left atrioventricular valve after atrioventricular septal defect correction with 4D Flow cardiovascular magnetic resonance and retrospective valve tracking

Background

To characterize and directly quantify regurgitant jets of left atrioventricular valve (LAVV) in patients with corrected atrioventricular septal defect (AVSD) by four-dimensional (4D)Flow Cardiovascular Magnetic Resonance (CMR), streamline visualization and retrospective valve tracking.

Methods

Medical ethical committee approval and informed consent from all patients or their parents were obtained. In 32 corrected AVSD patients (age 26 ± 12 years), echocardiography and whole-heart 4DFlow CMR were performed. Using streamline visualization on 2- and 4-chamber views, the angle between regurgitation and annulus was followed throughout systole. On through-plane velocity-encoded images reformatted perpendicular to the regurgitation jet the cross-sectional jet circularity index was assessed and regurgitant volume and fraction were calculated. Correlation and agreement between different techniques was performed with Pearson’s r and Spearman’s rho correlation and Bland-Altman analysis.

Results

In 8 patients, multiple regurgitant jets over the LAVV were identified. Median variation in regurgitant jet angle within patients was 36°(IQR 18–64°) on the 2-chamber and 30°(IQR 20–40°) on the 4-chamber. Regurgitant jets had a circularity index of 0.61 ± 0.16. Quantification of the regurgitation volume was feasible with 4DFlow CMR with excellent correlation between LAVV effective forward flow and aortic flow (r = 0.97, p < 0.001) for internal validation and moderate correlation with planimetry derived regurgitant volume (r = 0.65, p < 0.001) and echocardiographic grading (rho = 0.51, p = 0.003).

Conclusions

4DFlow CMR with streamline visualization revealed multiple, dynamic and eccentric regurgitant jets with non-circular cross-sectional shape in patients after AVSD correction. 4DFlow with retrospective valve tracking allows direct and accurate quantification of the regurgitation of these complex jets.     

Use of a sensitive bioimmunoabsorbent assay to isolate and characterize monoclonal antibodies to biologically active human erythropoietin

At present, one of the most sensitive assays for human erythropoietin (Ep) is a bioassay that measures the Ep-dependent proliferation of spleen cells from phenylhydrazine-treated mice after 24 hours in culture. We describe how this assay can be used as the basis of a very sensitive method for detecting mouse antibodies to biologically active human Ep. In this procedure, microtiter wells are first coated with goat anti-mouse Ig antibody, then treated with mouse antibodies (serum or hybridoma culture supernatants), and finally incubated with a fixed amount of pure human Ep. Specific binding of anti-Ep antibodies is detected by adding spleen cells from phenylhydrazine-treated mice to the wells and measuring the ability of the cells to incorporate 3H- thymidine 24 hours later. This bioimmunosorbent assay (BISA) revealed the presence of anti-EP antibodies in sera from mice immunized with either pure human urinary Ep or a synthetic dodecapeptide corresponding to the aminoterminal region of Ep and in the culture supernatants from three of eight stable anti-Ep antibody-producing hybridoma cell lines that we have isolated. The three monoclonal antibodies showed similar reactivities in the BISA, but showed different affinities for Ep, with Kd values of approximately 0.7, 8, and 240 nmol/L, respectively. Further studies showed that all antibodies were capable of neutralizing Ep bioactivity and of binding 125I-labeled Ep in a radioimmunosorbent assay (RIA) but were virtually unreactive to Ep adsorbed to the bottom of enzyme-linked immunosorbent assay (ELISA) wells. Our results suggest that the BISA strategy may be an important complement to conventional RIA and ELISA techniques for identification of monoclonal antibodies specific for biologically active growth factors.     

Purification and properties of bacterially synthesized human granulocyte-macrophage colony stimulating factor

Human granulocyte-macrophage colony stimulating factor (GM-CSF) has been synthesized in high yield using a temperature inducible plasmid in Escherichia coli. The human GM-CSF is readily isolated from the bacterial proteins because of its differential solubility and chromatographic properties. The bacterially synthesized form of the human GM-CSF contains an extra methionine residue at position 1, but otherwise it is identical to the polypeptide predicted from the cDNA sequence. The specific activity of 2.9 X 10(7) units/mg of protein for purified bacterially synthesized human GM-CSF indicates that despite the lack of glycosylation, the molecule is substantially in its native conformation. This molecule stimulated the same number and type of both seven- and 14-day human bone marrow colonies as the CSF alpha preparation from human placental conditioned medium. Human GM-CSF had no activity on murine bone marrow or murine leukemic cells. There was no detectable, direct stimulation of adult human erythroid burst forming units (BFU-E) by the bacterially synthesized human GM-CSF. Although impure preparations containing native human GM-CSF (eg, human placental conditioned medium) stimulated the formation of mixed colonies, even in the presence of erythropoietin, the bacterially synthesized human GM-CSF failed to stimulate the formation of mixed colonies from adult human bone marrow cells. The bacterially synthesized human GM-CSF increased N-formyl-methionyl-leucyl- phenylalanine (FMLP)-induced superoxide production and lysozyme secretion. Antibody-dependent cytotoxicity and phagocytosis by human neutrophils was stimulated by the bacterially synthesized human GM-CSF and eosinophils were also activated in the antibody-dependent cytotoxicity assay.     

The phytoconstituents and the comparative effects of aqueous extract of Irvingia gabonensis seeds and proviron on the biochemical parameters of male guinea pigs

ObjectiveTo investigate the phytochemical screening and the effects of the aqueous extracts of the seeds of Irvingia gabonensis on the biochemical parameters of male guinea pigs.MethodsThe biochemical parameters were assayed using Randox Diagnostic kits, Phenolphthalein method and colorimetric method. The phytochemical screening was carried out using standard procedures.ResultsPhytochemical investigations revealed the presence of flavonoids, tannins, carbohydrate, alkaloids, terpenoids, steroids, volatile oils, saponins and cardiac glycosides. The aqueous extract of Irvingia gabonensis seeds (50–400 mg/kg) caused a statistically significant (P<0.05 ANOVA) decrease in the levels of total cholesterol, urea, uric acid, total protein, prostatic, alkaline, and acid phosphatases. The highest reduction effect was obtained with uric acid at 400 mg/kg of Irvingia gabonensis extract while the least effect was observed in total cholesterol. These effects were dose-and time-dependent.ConclusionsThis shows that the seeds of Irvingia gabonensis have hepatoprotective, nephroprotective and cardio protective properties. The study therefore, supports the claims on the use of the seeds of this plant by traditional medicine practitioners as a hepatoprotective and nephroprotective agent. Although further studies need to be done to isolate, identify and characterize the active principles in the seeds of this plant.     

Eliminating Health Disparities Through Transdisciplinary Research, Cross-Agency Collaboration, and Public Participation

Despite efforts to the contrary, disparities in health and health care persist in the United States. To solve this problem, federal agencies representing different disciplines and perspectives are collaborating on a variety of transdisciplinary research initiatives. The most recent of these initiatives was launched in 2006 when the Centers for Disease Control and Prevention''s Office of Public Health Research and the Department of Health and Human Services’ Office of Minority Health brought together federal partners representing a variety of disciplines to form the Federal Collaboration on Health Disparities Research (FCHDR).FCHDR collaborates with a wide variety of federal and nonfederal partners to support and disseminate research that aims to reduce or eliminate disparities in health and health care. Given the complexity involved in eliminating health disparities, there is a need for more transdisciplinary, collaborative research, and facilitating that research is FCHDR''s mission.

“The greatest single challenge facing our globalized world is to combat and eradicate its disparities.”—Nelson Mandela¹

OVER THE LAST FEW DECADES, there has been a dramatic decline in disease mortality for many Americans.^2–5 However, some groups of Americans have not fully benefited from this progress, as evidenced by their continued higher disease incidence, morbidity, and mortality.^6–9 Racial and ethnic minorities, persons with disabilities, women, the medically underserved, and the economically disadvantaged, among others, face many obstacles to accessing and receiving effective health services, such as health promotion, disease prevention, early detection, and high-quality medical treatment.^10–12 As a result, many experience suboptimal health outcomes. Barriers to optimum health include inadequate purchasing power; being uninsured and underinsured; geographic, cultural, and language barriers; racial bias; and stereotyping. These factors are key determinants of health disparities.^10–13To better address these determinants, in 2000 the federal government established the elimination of health disparities as a goal of the Healthy People 2010 initiative; as part of this effort, the government made a large investment in research into health disparities and health equity.^14–16 Although this work yielded important knowledge about the complex interplay of factors that contribute to health disparities, a midcourse review of Healthy People 2010 showed limited success in reducing health disparities in communities across our nation.¹⁷ In recognition of the need for greater success, the absence of a broad collaborative approach across the federal government, and the potential benefits of multiagency collaboration, the Federal Collaboration on Health Disparities Research (FCHDR) was launched in 2006. Given the complexity involved in eliminating health disparities, there is a need for more innovative approaches derived from transdisciplinary research and involving multiple federal agencies from different disciplines.     

Cyclic AMP-mediated chloride secretion is induced by prostaglandin F2α in human isolated colon

Background and purpose:

Prostaglandin F_2α (PGF_2α) is implicated in the pathogenesis of inflammatory bowel disease and colorectal cancer. This study investigates the effects of PGF_2α on electrophysiological parameters in isolated human colonic mucosa.

Experimental approach:

Ion transport was measured as changes in short-circuit current across human colonic epithelia mounted in Ussing chambers. Colonic crypts were isolated by calcium chelation and cyclic adenosine monophosphate (cAMP) was measured by ELISA.

Key Results:

PGF_2α stimulated chloride secretion in a concentration-dependent manner with an EC₅₀ of 130 nM. The PGF_2α induced increase in chloride secretion was inhibited by AL8810 (10 µM), a specific PGF_2α receptor antagonist. In addition, PGF_2α (1 µM) significantly increased levels of cAMP in isolated colonic crypts.

Conclusions and implications:

PGF_2α stimulated chloride secretion in samples of human colon in vitro through a previously unrecognizd cAMP-mediated mechanism. These findings have implications for inflammatory states.     

BGC20-1531, a novel,potent and selective prostanoid EP4 receptor antagonist: a putative new treatment for migraine headache

Background and purpose:

Prostanoid EP₄ receptor antagonists may have therapeutic utility in the treatment of migraine since EP₄ receptors have been shown to be involved in prostaglandin (PG)E₂-induced cerebral vascular dilatation, which may be an important contributor to migraine pain. This study reports the pharmacological characterization of BGC20-1531, a novel EP₄ receptor antagonist.

Experimental approach:

BGC20-1531 was characterized in radioligand binding and in vitro functional assays employing recombinant and native EP₄ receptors. Changes in canine carotid haemodynamics were used to assess the pharmacodynamic profile of BGC20-1531 in vivo.

Key results:

BGC20-1531 exhibited high affinity at recombinant human EP₄ receptors expressed in cell lines (pK_B 7.6) and native EP₄ receptors in human cerebral and meningeal artery (pK_B 7.6–7.8) but showed no appreciable affinity at a wide range of other receptors (including other prostanoid receptors), channels, transporters and enzymes (pKi < 5). BGC20-1531 competitively antagonized PGE₂-induced vasodilatation of human middle cerebral (pK_B 7.8) and meningeal (pK_B 7.6) arteries in vitro, but had no effect on responses induced by PGE₂ on coronary, pulmonary or renal arteries in vitro. BGC20-1531 (1–10 mg·kg⁻¹ i.v.) caused a dose-dependent antagonism of the PGE₂-induced increase in canine carotid blood flow in vivo.

Conclusions and implications:

BGC20-1531 is a potent and selective antagonist at EP₄ receptors in vitro and in vivo, with the potential to alleviate the symptoms of migraine that result from cerebral vasodilatation. BGC20-1531 is currently in clinical development for the treatment of migraine headache.