Patient and implant survival following 4323 total hip replacements for acute femoral neck fracture: a retrospective cohort study using National Joint Registry data.

United Kingdom National Institute for Health and Clinical Excellence guidelines recommend the use of total hip replacement (THR) for displaced intracapsular fractures of the femoral neck in cognitively intact patients, who were independently mobile prior to the injury. This study aimed to analyse the risk factors associated with revision of the implant and mortality following THR, and to quantify risk. National Joint Registry data recording a THR performed for acute fracture of the femoral neck between 2003 and 2010 were analysed. Cox proportional hazards models were used to investigate the extent to which risk of revision was related to specific covariates. Multivariable logistic regression was used to analyse factors affecting peri-operative mortality (< 90 days). A total of 4323 procedures were studied. There were 80 patients who had undergone revision surgery at the time of censoring (five-year revision rate 3.25%, 95% confidence interval 2.44 to 4.07) and 137 patients (3.2%) patients died within 90 days. After adjusting for patient and surgeon characteristics, an increased risk of revision was associated with the use of cementless prostheses compared with cemented (hazard ratio (HR) 1.33, p = 0.021). Revision was independent of bearing surface and head size. The risk of mortality within 90 days was significantly increased with higher American Society of Anesthesiologists (ASA) grade (grade 3: odds ratio (OR) 4.04, p < 0.001; grade 4/5: OR 20.26, p < 0.001; both compared with grades 1/2) and older age (≥ 75 years: OR 1.65, p = 0.025), but reduced over the study period (9% relative risk reduction per year). THR is a good option in patients aged < 75 years and with ASA 1/2. Cementation of the femoral component does not adversely affect peri-operative mortality but improves survival of the implant in the mid-term when compared with cementless femoral components. There are no benefits of using head sizes > 28 mm or bearings other than metal-on-polyethylene. More research is required to determine the benefits of THR over hemiarthroplasty in older patients and those with ASA grades > 2.

THA with the ABG I prosthesis at 15 years. Excellent survival with minimal osteolysis.

UNLABELLED: Following recent reports of poor results with the hydroxyapatite-coated ABG I prosthesis, we report the survival of a series of 63 patients (69 hips) at a mean of 15 years (range, 13-17 years). In total, eight patients had revision procedures. The reason for revision was acetabular loosening in all cases. In only one case was there associated clinical and radiographic loosening of the femoral stem. The 15-year survival of the acetabular component was 86.9% (95% confidence interval, 71.7%-96.0%) and the 15-year survival of the femoral component was 98.6% (95% confidence interval, 88.8%-100.0%). Periacetabular osteolysis was seen in 10 of 59 (17%) surviving hips. In these hips the components remained well fixed owing to the remaining bone-component contact. There was no difference in the Oxford hip score between patients with well-fixed hips and evidence of osteolysis and patients with hips without evidence of osteolysis. Multivariate analysis failed to reveal any factors associated with the presence of osteolysis (gender, age at primary surgery, Oxford hip score, cup abduction, and acetabular polyethylene wear rates). The ABG I prosthesis continues to show excellent long-term results. Ongoing radiographic review is recommended to detect progressive osteolysis that otherwise remains clinically silent until failure. LEVEL OF EVIDENCE: Level IV, Case series. See Guidelines for Authors for a complete description of levels of evidence.

Therapeutic potential of RhoA/Rho kinase inhibitors in pulmonary hypertension.

A burgeoning body of evidence suggests that RhoA/Rho kinase (ROCK) signalling plays an important role in the pathogenesis of various experimental models of pulmonary hypertension (PH), including chronic hypoxia-, monocrotaline-, bleomycin-, shunt- and vascular endothelial growth factor receptor inhibition plus chronic hypoxia-induced PH. ROCK has been incriminated in pathophysiologic events ranging from mediation of sustained abnormal vasoconstriction to promotion of vascular inflammation and remodelling. In addition, the 3-hydroxy-3-methylglutaryl CoA reductase inhibitors, statins, which inhibit activation of RhoA by preventing post-translational isoprenylation of the protein and its translocation to the plasma membrane ameliorate PH in several different rat models, and may also be effective in PH patients. Also, phosphorylation of RhoA and prevention of its translocation to the plasma membrane are involved in the protective effect of the type 5-PDE inhibitor, sildenafil, against hypoxia- and bleomycin-induced PH. Collectively, these and other observations indicate that independent of the cause of PH, activation of the RhoA/ROCK pathway serves as a point of convergence of various signalling cascades in the pathogenesis of the disease. We propose that ROCK inhibitors and other drugs that inhibit this pathway might be useful in the treatment of various forms of PH.

Role of computerised tomography in management of intra-articular fractures of the os calcis.

This study aimed to look at the role played by the CT scan in decision making in the management of intra-articular fractures of the calcaneum. Twenty-four patients with intra-articular fractures of the calcaneum were included. Their initial radiographs and CT films were blinded and assessed by three independent observers. Based on this they were selected for operative or non-operative management. The actual management was also recorded. The data were then subjected to statistical analysis to look at the association between the decision from radiograph, that from the CT scan and the actual management undertaken. Non-parametric tests for related samples were performed to look at the association between the actual management and the decisions made by assessing the radiographs and the CT scans. For all three observers, there was no significant difference between the actual management and decisions made by assessing the plain radiographs or the CT scan. There was also no significant difference between the radiograph-based and the CT-based decisions. However, the Cochran Q test showed that there was significant variation among the three observers for the CT-based assessment. Our results, show that the CT scan should only be done when a definite decision is made to operate on a patient, based on plain radiographs. Calcaneal fractures which are selected for non-operative management, based on X rays, should not have a CT scan as a routine as it provides no valuable additional information affecting the management decision.

Osteotomy for congenital elevation of the scapula (Sprengel's deformity).

We report 12 consecutive cases of vertical scapular osteotomy to correct Sprengel's deformity, performed during a 16-year period, with a mean follow-up of 10.4 years. The mean increase in abduction of the shoulder was 53 degrees . The cosmetic appearance improved by a mean of 1.5 levels on the Cavendish scale. Neither function nor cosmesis deteriorated with time. We recommend the procedure for correction of moderate deformities with a functional deficit.

Role of endothelin-1 in lung disease.

Endothelin-1 (ET-1) is a 21 amino acid peptide with diverse biological activity that has been implicated in numerous diseases. ET-1 is a potent mitogen regulator of smooth muscle tone, and inflammatory mediator that may play a key role in diseases of the airways, pulmonary circulation, and inflammatory lung diseases, both acute and chronic. This review will focus on the biology of ET-1 and its role in lung disease.

Upregulation of nitric oxide synthase in mice with severe hypoxia-induced pulmonary hypertension.

BACKGROUND: The importance of nitric oxide (NO) in hypoxic pulmonary hypertension has been demonstrated using nitric oxide synthase (NOS) knockout mice. In that model NO from endothelial NOS (eNOS) plays a central role in modulating pulmonary vascular tone and attenuating hypoxic pulmonary hypertension. However, the normal regulation of NOS expression in mice following hypoxia is uncertain. Because genetically engineered mice are often utilized in studies of NO, we conducted the present study to determine how hypoxia alters NOS expression in wild-type mice. METHOD: Mice were exposed to sea level, ambient conditions (5280 feet) or severe altitude (17,000 feet) for 6 weeks from birth, and hemodynamics and lung NOS expression were assessed. RESULTS: Hypoxic mice developed severe pulmonary hypertension (right ventricular systolic pressure [RVsP] 60 mmHg) as compared with normoxic mice (27 mmHg). Using quantitative reverse-transcription PCR, it was found that expressions of eNOS and inducible NOS (iNOS) increased 1.5-fold and 3.5-fold, respectively, in the lung. In addition, the level of lung eNOS protein was increased, neuronal NOS (nNOS) protein was unchanged, and iNOS was below the limit of detection. Immunohistochemistry demonstrated no change in lung iNOS or nNOS staining in either central or peripheral areas, but suggested increased eNOS in the periphery following hypoxia. CONCLUSION: In mice, hypoxia is associated with increases in lung eNOS, possibly in iNOS, but not in nNOS; this suggests that the pattern of lung NOS expression following hypoxia must be considered in studies using genetically engineered mice.

Mild hypoxia causes severe pulmonary hypertension in fawn-hooded but not in Tester Moriyama rats.

The purpose of this study was to test whether the Tester Moriyama rat (TMR), a strain that has a serotonin platelet storage-pool deficiency similar to that of the fawn-hooded rat (FHR), develops severe pulmonary hypertension (PH) upon exposure to mild hypoxia. We compared hemodynamic parameters in catheterized 10-week-old FHR, TMR, and control Wistar rats that had been raised from birth to 10 weeks of age under normoxia (PI(O(2)) approximately 150 mmHg) or mild hypobaric hypoxia (PI(O(2)) approximately 120 mmHg). Mean pulmonary artery pressure and right ventricle to left ventricle plus septum weight ratio were much higher in the mildly hypoxic FHR compared with the normoxic FHR. These parameters were only increased slightly by exposure to mild hypoxia in the TMR and Wistar rats. Mild hypoxia did not affect mean systemic artery pressure in any of the rat strains. Exposure of FHR to mild hypoxia from 4 to 10 weeks of age did not lead to development of PH. Endothelin-1 (ET-1) mRNA and peptide levels were increased in the hypertensive lungs of mildly hypoxic FHR compared with the normotensive lungs of normoxic FHR, and of normoxic and mildly hypoxic TMR and Wistar rats. These results suggest that mild hypoxia causes severe PH and upregulation of lung ET-1 expression in neonatal FHR but not in neonatal TMR, and that the period from birth to 4 weeks of age is critical for the development of the severe PH in the FHR. A serotonin PSPD does not predispose rats to hypoxia-induced PH.

Endothelin B receptor deficiency potentiates ET-1 and hypoxic pulmonary vasoconstriction.

Endothelin (ET)-1 contributes to the regulation of pulmonary vascular tone by stimulation of the ET(A) and ET(B) receptors. Although activation of the ET(A) receptor causes vasoconstriction, stimulation of the ET(B) receptors can elicit either vasodilation or vasoconstriction. To examine the physiological role of the ET(B) receptor in the pulmonary circulation, we studied a genetic rat model of ET(B) receptor deficiency [transgenic(sl/sl)]. We hypothesized that deficiency of the ET(B) receptor would predispose the transgenic(sl/sl) rat lung circulation to enhanced pulmonary vasoconstriction. We found that the lungs of transgenic(sl/sl) rats are ET(B) deficient because they lack ET(B) mRNA in the pulmonary vasculature, have minimal ET(B) receptors as determined with an ET-1 radioligand binding assay, and lack ET-1-mediated pulmonary vasodilation. The transgenic(sl/sl) rats have higher basal pulmonary arterial pressure and vasopressor responses to brief hypoxia or ET-1 infusion. Plasma ET-1 levels are elevated and endothelial nitric oxide synthase protein content and nitric oxide production are diminished in the transgenic(sl/sl) rat lung. These findings suggest that the ET(B) receptor plays a major physiological role in modulating resting pulmonary vascular tone and reactivity to acute hypoxia. We speculate that impaired ET(B) receptor activity can contribute to the pathogenesis of pulmonary hypertension.

Nitric oxide production in the hypoxic lung.

Nitric oxide (NO) is a potent vasodilator and inhibitor of vascular remodeling. Reduced NO production has been implicated in the pathophysiology of pulmonary hypertension, with endothelial NO synthase (NOS) knockout mice showing an increased risk for pulmonary hypertension. Because molecular oxygen (O2) is an essential substrate for NO synthesis by the NOSs and biochemical studies using purified NOS isoforms have estimated the Michaelis-Menten constant values for O2 to be in the physiological range, it has been suggested that O2 substrate limitation may limit NO production in various pathophysiological conditions including hypoxia. This review summarizes numerous studies of the effects of acute and chronic hypoxia on NO production in the lungs of humans and animals as well as in cultured vascular cells. In addition, the effects of hypoxia on NOS expression and posttranslational regulation of NOS activity by other proteins are also discussed. Most studies found that hypoxia limits NO synthesis even when NOS expression is increased.

Closed reduction of the traumatically dislocated hip: a new technique.

Traumatic dislocation of the hip joint without associated fracture is not common. It is the result of high energy transfer usually a RTA or fall from a height. It is a true emergency, and the joint should be relocated within 6h. Failure to do so increases the risk of avascular necrosis of the femoral head with resultant early degenerative joint disease often in an otherwise fit young patient.

Inhibition of K(Ca) channels restores blunted hypoxic pulmonary vasoconstriction in rats with cirrhosis.

Rats with liver cirrhosis exhibit the hepatopulmonary syndrome composed of blunted hypoxic pulmonary vasoconstriction and arterial hypoxemia. The purpose of this study was to investigate the roles of nitric oxide (NO) and endothelin-1 (ET-1) in the blunted hypoxic pressor response (HPR) in rats with common bile duct ligation (CBDL). Lungs from CBDL rats exhibited markedly blunted HPR, increased endothelial NO synthase (NOS) protein expression, and decreased ET-1 mRNA and peptide expression. The blunted HPR was not reversed by sequential NOS and soluble guanylyl cyclase inhibition by nitro-L-arginine and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), respectively, or by NOS inhibition combined with ET-1 addition. The blunted HPR was not due to a generalized inability to vasoconstrict because perfusion pressure was equally elevated by increased perfusate KCl in CBDL and sham lungs. After KCl vasoconstriction, HPR was potentiated and did not differ between CBDL and sham lungs. Blunted HPR was also completely restored in CBDL lungs treated with nitro-L-arginine, ODQ, and the Ca(2+)-activated K(+) channel blockers apamin and charybdotoxin. These results indicate that although CBDL-induced liver cirrhosis is associated with increased NO and decreased ET-1 in the lung, the blunted HPR is a result of additional factors and appears to involve Ca(2+)-activated K(+) channel activation.

Neonatal dexamethasone treatment increases the risk for pulmonary hypertension in adult rats.

Dexamethasone (Dex) treatment during a critical period of lung development causes lung hypoplasia in infant rats. However, the effects of Dex on the pulmonary circulation are unknown. To determine whether Dex increases the risk for development of pulmonary hypertension, we treated newborn Sprague-Dawley rats with Dex (0.25 microg/day, days 3-13). Litters were divided equally between Dex-treated and vehicle control (ethanol) rats. Rats were raised in either room air until 10 wk of age (normoxic groups) or room air until 7 wk of age and then in a hypoxia chamber (inspired O(2) fraction = 0.10; hypoxic groups) for 3 wk to induce pulmonary hypertension. Compared with vehicle control rats, Dex treatment of neonatal rats reduced alveolarization (by 42%; P < 0.05) and barium-filled pulmonary artery counts (by 37%; P < 0.05) in 10-wk-old adults. Pulmonary arterial pressure and the ratio of right ventricle to left ventricle plus septum weights (RV/LV+S) were higher in 10-wk-old Dex-treated normoxic rats compared with those in normoxic control rats (by 16 and 16% respectively; P < 0.05). Small pulmonary arteries of adult normoxic Dex-treated rats showed increased vessel wall thickness compared with that in control rats (by 15%; P < 0.05). After 3 wk of hypoxia, RV/LV+S values were 36% higher in rats treated with Dex in the neonatal period compared with those in hypoxic control rats (P < 0.05). RV/LV+S was 42% higher in hypoxic control rats compared with those in normoxic control rats (P < 0.05). We conclude that Dex treatment of neonatal rats caused sustained lung hypoplasia and increased pulmonary arterial pressures and augmented the severity of hypoxia-induced pulmonary hypertension in adult rats.

Mechanism of hypoxic pulmonary vasoconstriction involves ET(A) receptor-mediated inhibition of K(ATP) channel.

There is controversy on the role of endothelin (ET)-1 in the mechanism of hypoxic pulmonary vasoconstriction (HPV). Although HPV is inhibited by ET-1 subtype A (ET(A))-receptor antagonists in animals, it has been reported that ET(A)-receptor blockade does not affect HPV in isolated lungs. Thus we reassessed the role of ET-1 in HPV in both rats and isolated blood- and physiological salt solution (PSS)-perfused rat lungs. In rats, the ET(A)-receptor antagonist BQ-123 and the nonselective ET(A)- and ET(B)-receptor antagonist PD-145065, but not the ET(B)-receptor antagonist BQ-788, inhibited HPV. Similarly, BQ-123, but not BQ-788, attenuated HPV in blood-perfused lungs. In PSS-perfused lungs, either BQ-123, BQ-788, or the combination of both attenuated HPV equally. Inhibition of HPV by combined BQ-123 and BQ-788 in PSS-perfused lungs was prevented by costimulation with angiotensin II. The ATP-sensitive K(+) (K(ATP))-channel blocker glibenclamide also prevented inhibition of HPV by BQ-123 in both lungs and rats. These results suggest that ET-1 contributes to HPV in both isolated lungs and intact animals through ET(A) receptor-mediated suppression of K(ATP)-channel activity.

Occult elbow dislocation: a rare cause of upper limb arterial insufficiency.

We present a case of vascular injury resulting from occult dislocation of the elbow joint. At last review 46 cases of brachial artery injury with concomitant dislocation have been reported (10), all in small series and case reports. In all the dislocation was clinically or radiologically evident.

Nitric oxide synthase in pulmonary hypertension: lessons from knockout mice.

Nitric oxide (NO) is implicated in a wide variety of biological roles. NO is generated from three nitric oxide synthase (NOS) isoforms: neuronal (nNOS), inducible (iNOS), and endothelial (eNOS) all of which are found in the lung. While there are no isoform-specific inhibitors of NOS, the recent development and characterization of mice deficient in each of the NOS isoforms has allowed for more comprehensive study of the importance of NO in the lung circulation. Studies in the mouse have identified the role of NO from eNOS in modulating pulmonary vascular tone and in attenuating the development of chronic hypoxic pulmonary hypertension.

Relative contributions of endothelial, inducible, and neuronal NOS to tone in the murine pulmonary circulation.

Nitric oxide plays an important role in modulating pulmonary vascular tone. All three isoforms of nitric oxide synthase (NOS), neuronal (nNOS, NOS I), inducible (iNOS, NOS II), and endothelial (eNOS, NOS III), are expressed in the lung. Recent reports have suggested an important role for eNOS in the modulation of pulmonary vascular tone chronically; however, the relative contribution of the three isoforms to acute modulation of pulmonary vascular tone is uncertain. We therefore tested the effect of targeted disruption of each isoform on pulmonary vascular reactivity in transgenic mice. Isolated perfused mouse lungs were used to evaluate the effect of selective loss of pulmonary nNOS, iNOS, and eNOS with respect to hypoxic pulmonary vasoconstriction (HPV) and endothelium-dependent and -independent vasodilation. eNOS null mice had augmented HPV (225 +/- 65% control, P < 0.02, mean +/- SE) and absent endothelium-dependent vasodilation, whereas endothelium-independent vasodilation was preserved. HPV was minimally elevated in iNOS null mice and normal in nNOS null mice. Both nNOS and iNOS null mice had normal endothelium-dependent vasodilation. In wild-type lungs, nonselective NOS inhibition doubled HPV, whereas selective iNOS inhibition had no detectable effect. In intact, lightly sedated mice, right ventricular systolic pressure was elevated in eNOS-deficient (42.3 +/- 1.2 mmHg, P < 0.001) and, to a lesser extent, in iNOS-deficient (37.2 +/- 0.8 mmHg, P < 0.001) mice, whereas it was normal in nNOS-deficient mice (30.9 +/- 0.7 mmHg, P = not significant) compared with wild-type controls (31.3 +/- 0.7 mmHg). We conclude that in the normal murine pulmonary circulation 1) nNOS does not modulate tone, 2) eNOS-derived nitric oxide is the principle mediator of endothelium-dependent vasodilation in the pulmonary circulation, and 3) both eNOS and iNOS play a role in modulating basal tone chronically.

Enhanced ET(A)-receptor-mediated inhibition of K(v) channels in hypoxic hypertensive rat pulmonary artery myocytes.

Endothelin (ET)-1 has been implicated as a critical mediator in the pathogenesis of hypoxic pulmonary hypertension. We questioned whether, during exposure to chronic hypobaric hypoxia, rat pulmonary artery smooth muscle cells (PASMC) became sensitized to ET-1. Two effects of ET-1, inhibition of voltage-gated K(+) (K(v)) channels and release of intracellular Ca(2+), were studied using whole cell patch clamp and single cell indo 1 fluorescence, respectively. In both normotensive and chronically hypoxic-hypertensive PASMC, ET-1 caused concentration-dependent inhibition of voltage-gated K(+) current [I(K(v))], with maximum inhibition of 12-18% seen at a concentration of 0.1-1 nM. Although the chronically hypoxic-hypertensive PASMC was no more susceptible to ET-1-mediated I(K(v)) inhibition, a switch in coupling between ET-1 and I(K(v)) from ET(B) to ET(A) receptors occurred. This switch in receptor coupling, combined with reduced I(K(v)) density and increased ET-1 production in the hypoxic rat lung, may help explain the ability of ET(A)-receptor blockers to attenuate the development of hypoxic pulmonary hypertension in vivo.

Hypoxia inhibits increased ETB receptor-mediated NO synthesis in hypertensive rat lungs.

Although hypertensive lungs of chronically hypoxic rats express increased levels of nitric oxide (NO) synthases (NOSs) and produce increased amounts of NO-containing compounds (NOx) during normoxic ventilation, the level of NO production during hypoxic exposure is unclear. Because hypoxia inhibits NO synthesis in normotensive lungs, we investigated whether hypoxic ventilation inhibited NO synthesis in isolated hypertensive lungs and chronically hypoxic rats. Measurement of perfusate NOx concentration in hypertensive lungs from male rats exposed to 4 wk of hypobaric hypoxia showed that basal NOx production was reduced during hypoxic (0% O2) vs. normoxic (21% O2) ventilation. Similarly, plasma NOx concentration was lower in chronically hypoxic rats breathing 10% O2 than in those breathing 21% O2. Hypoxic inhibition of lung NOx production was not prevented by supplementary L-arginine or tetrahydrobiopterin and was not mimicked by inhibition of Ca2+ influx. However, it was mimicked by inhibition of constitutive NOS with NG-monomethyl-L-arginine and chelation of intracellular Ca2+. The endothelin type B-receptor antagonist BQ-788 prevented the increases in NOx production associated with normoxic ventilation in both isolated hypertensive lungs and intact chronically hypoxic rats. These results suggest that a reduced supply of the cosubstrate molecular O2 to NOS counteracts an endothelin type B receptor-mediated stimulation of NO synthesis in hypertensive rat lungs. Thus, despite increased NOS protein in the lungs and pulmonary arteries of chronically hypoxic rats, direct hypoxic inhibition of NO production may contribute to the development of pulmonary hypertension.