Gas exchange and breathing pattern in women with postmenopausal bone fragility.

BACKGROUND: Little is known about the relationship between bone fragility and respiratory function. We hypothesized that women with osteoporosis or osteopenia, without cardio-pulmonary disease, have perturbations in the pattern of breathing and gas exchange. METHODS: In 44 women with bone fragility (BF, T score: < -1), and 20 anthropomorphically-matched control women (T score > -1) we compared pulmonary function tests, central respiratory drive (mouth occlusion pressure or P 0.1), pattern of breathing using optoelectronic plethysmograph and arterial blood gases at rest. RESULTS: Static pulmonary function was similar in BF subjects and controls. However, the arterial blood gas measurements differed significantly. The arterial pH was significantly higher in BF subjects than in controls (P < 0.001). The partial pressure of carbon dioxide (PaCO2) and oxygen (PaO2) in arterial blood were significantly lower in BF subjects than controls (P < 0.001 and P = 0.009, respectively). The BF subjects had a shorter inspiratory fraction compared with controls (P = 0.036). Moreover, T-scores were significantly inversely correlated with the alveolar-arterial gradient of oxygen (r = -0.5; P = 0.0003) and the arterial pH (r = -0.4; P = 0.002), and positively correlated with arterial PaO2 (r = 0.3; P = 0.01) and PaCO2 (r = 0.4; P = 0.002) among all subjects. CONCLUSION: In the absence of known cardio-pulmonary disease, BF is associated with statistically significant perturbations in gas exchange and alterations in the pattern of breathing including shortening of the inspiratory time.

Clinical outcomes of bilateral single-stage unicompartmental knee arthroplasty.

BACKGROUND: Deciding whether to treat patients with bilateral arthritis with two-stage or bilateral single-stage arthroplasties is a cause of considerable debate in orthopaedic surgery. METHODS: A total of 394 cemented Unicompartmental Knee Arthroplasties (UKA) were performed in this unit between 2006 and 2010. A retrospective review identified 38 patients (76 knees) who underwent bilateral Single-Stage Sequential UKA, performed by a single surgeon. RESULTS: The mean BMI was 29.8 and the majority of patients were ASA grade 2. The mean duration of follow-up was 30 months. The mean total tourniquet time was 83 min. The mean post-operative haemoglobin was 11.8 and no patient required blood transfusion. The mean time to mobilisation was 18 h and the average length of stay was 3.5 days. This compares favourably with an institutional average length of stay of two days for a single UKA. There was a significant improvement in the mean pre- to post-operative OKS (from 14 to 34, p<0.0001). One patient required operative fixation of a tibial plateau fracture after sustaining a mechanical fall two months following surgery. There were no other major complications, including thrombo-embolic events or deep infections. Two patients required excision of a superficial suture granuloma. CONCLUSIONS: Bilateral Single-Stage Sequential UKAs provide significant improvement in patient function and can be performed safely with a low complication rate. Patients can benefit from a single hospital admission and anaesthetic whilst the shorter total in-patient stay reduces costs incurred by the hospital. LEVEL OF EVIDENCE: IV.

Are current thrombo-embolic prophylaxis guidelines applicable to unicompartmental knee replacement?

Symptomatic and asymptomatic deep-vein thrombosis (DVT) is a common complication of knee replacement, with an incidence of up to 85% in the absence of prophylaxis. National guidelines for thromboprophylaxis in knee replacement are derived from total knee replacement (TKR) data. No guidelines exist specific to unicompartmental knee replacement (UKR). We investigated whether the type of knee arthroplasty (TKR or UKR) was related to the incidence of DVT and discuss the applicability of existing national guidelines for prophylaxis following UKR. Data were collected prospectively on 3449 knee replacements, including procedure type, tourniquet time, surgeon, patient age, use of drains and gender. These variables were related to the incidence of symptomatic DVT. The overall DVT rate was 1.6%. The only variable that had an association with DVT was operation type, with TKR having a higher incidence than UKR (2.2% versus 0.3%, p < 0.001). These data show that the incidence of DVT after UKR is both clinically and statistically significantly lower than that after TKR. TKR and UKR patients have different risk profiles for symptomatic DVT. The risk-benefit ratio for TKR that has been used to produce national guidelines may not be applicable to UKR. Further research is required to establish the most appropriate form of prophylaxis for UKR.

Orthopaedic surgeons: as strong as an ox and almost twice as clever? Multicentre prospective comparative study.

OBJECTIVE: To compare the intelligence and grip strength of orthopaedic surgeons and anaesthetists. DESIGN: Multicentre prospective comparative study. SETTING: Three UK district general hospitals in 2011. PARTICIPANTS: 36 male orthopaedic surgeons and 40 male anaesthetists at consultant or specialist registrar grade. MAIN OUTCOME MEASURES: Intelligence test score and dominant hand grip strength. RESULTS: Orthopaedic surgeons had a statistically significantly greater mean grip strength (47.25 (SD 6.95) kg) than anaesthetists (43.83 (7.57) kg). The mean intelligence test score of orthopaedic surgeons was also statistically significantly greater at 105.19 (10.85) compared with 98.38 (14.45) for anaesthetists. CONCLUSIONS: Male orthopaedic surgeons have greater intelligence and grip strength than their male anaesthetic colleagues, who should find new ways to make fun of their orthopaedic friends.

Early metallosis-related failure after total knee replacement: a report of 15 cases.

Metallosis is a rare cause of failure after total knee replacement and has only previously been reported when there has been abnormal metal-on-metal contact. We describe 14 patients (15 knees) whose total knee replacement required revision for a new type of early failure caused by extensive metallosis. A modification of a cementless rotating platform implant, which had previously had excellent long-term survival, had been used in each case. The change was in the form of a new porous-beaded surface on the femoral component to induce cementless fixation, which had been used successfully in the fixation of acetabular and tibial components. This modification appeared to have resulted in metallosis due to abrasive two-body wear. The component has subsequently been recalled and is no longer in use. The presentation, investigation, and findings at revision are described and a possible aetiology and its implications are discussed.

Factors affecting the incidence of infection in hip and knee replacement: an analysis of 5277 cases.

Infection remains a significant and common complication after joint replacement and there is debate about which contributing factors are important. Few studies have investigated the effect of the operating time on infection. We collected data prospectively from 5277 hip and knee replacements which included the type of procedure, the operating time, the use of drains, the operating theatre, surgeon, age and gender. In a subgroup of 3449 knee replacements further analysis was carried out using the tourniquet time in place of the operating time. These variables were assessed by the use of generalised linear modelling against superficial, deep or joint-space post-operative infection as defined by the Australian Surgical-Site Infection criteria. The overall infection rate was 0.98%. In the replacement data set both male gender (z = 3.097, p = 0.00195) and prolonged operating time (z = 4.325, p < 0.001) were predictive of infection. In the knee subgroup male gender (z = 2.250, p = 0.02447), a longer tourniquet time (z = 2.867, p = 0.00414) and total knee replacement (versus unicompartmental knee replacement) (z = -2.052, p = 0.0420) were predictive of infection. These findings support the view that a prolonged operating time and male gender are associated with an increased incidence of infection. Steps to minimise intra-operative delay should be instigated, and care should be exercised when introducing measures which prolong the duration of joint replacement.

Effects of 'bare below the elbows' policy on hand contamination of 92 hospital doctors in a district general hospital.

Despite a lack of evidence the UK's Department of Health introduced a policy of 'bare below the elbows' attire in order to try to reduce the incidence of nosocomial infection. This study investigates the link between this state of dress and hand contamination. A prospective observational study of doctors working in a district general hospital was carried out. The fingertips of each hand were imprinted onto culture medium, and resultant growth assessed for number of colony-forming units and presence of clinically significant pathogens or multiply resistant organisms. These findings were correlated with attire, grade, sex and specialty. Ninety-two doctors were recruited of whom 49 were 'bare below the elbows' compliant and 43 were not. There was no statistically significant difference between those doctors who were 'bare below the elbows' and those that were not, either for the number of colony-forming units or for the presence of clinically significant organisms. No multiply resistant organisms were cultured from doctors' hands. 'Bare below the elbows' attire is not related to the degree of contamination on doctors' fingertips or the presence of clinically significant pathogens. Further studies are required to establish whether investment in doctors' uniforms and patient education campaigns are worthwhile.

Survival following an acute coronary syndrome: a pet theory put to the test.

OBJECTIVE: The aim of this study was to revisit findings from previous studies reporting that pet ownership improves outcome following an admission for acute coronary syndrome (ACS). METHOD: Four hundred and twenty-four patients admitted to a cardiac unit with an ACS completed questions regarding pet ownership in hospital. Rates of cardiac death and readmission were assessed 1 year following hospitalization. RESULTS: Pet owners were more likely to experience a death or readmission following their hospitalization, after controlling for key psychosocial and medical covariates. When dog and cat owners were considered separately, cat ownership was significantly associated with increased risk of death or readmission. CONCLUSION: In this independent study, pet ownership at baseline, and cat ownership in particular, was associated with increased cardiac morbidity and mortality in the year following an admission for an acute coronary syndrome, a finding contrary to previous reports.

Total hip arthroplasty in Klippel-Trenaunay syndrome.

Klippel-Trenaunay syndrome patients often suffer degenerative joint disease at an early age. Performing arthroplasty in these patients is particularly difficult for a number of reasons. In this case report, we describe the second reported case of total hip replacement in Klippel-Trenaunay syndrome, using novel techniques to surmount the problems faced in this challenging condition.

Bioactive proteinase 3 on the cell surface of human neutrophils: quantification, catalytic activity, and susceptibility to inhibition.

Although proteinase 3 (PR3) is known to have the potential to promote inflammation and injure tissues, the biologic forms and function of PR3 in polymorphonuclear neutrophils (PMN) from healthy donors have received little attention. In this paper, we show that PMN contain 3.24 +/- SD 0.24 pg of PR3 per cell, and that the mean concentration of PR3 in azurophil granules of PMN is 13.4 mM. Low levels of PR3 are detectable on the cell surface of unstimulated PMN. Exposure of PMN to cytokines or chemoattractants alone induces modest (1.5- to 2.5-fold) increases in cell surface-bound PR3. In contrast, brief priming of PMN with cytokines, followed by activation with a chemoattractant, induces rapid and persistent, 5- to 6-fold increases in cell surface expression of PR3, while causing minimal free release of PR3. Membrane-bound PR3 on PMN is catalytically active against Boc-Alanine-Alanine-Norvaline-thiobenzyl ester and fibronectin, but in marked contrast to soluble PR3, membrane-bound PR3 is resistant to inhibition by physiologic proteinase inhibitors. PR3 appears to bind to the cell surface of PMN via a charge-dependent mechanism because exposure of fixed, activated PMN to solutions having increasing ionic strength results in elution of PR3, HLE, and CG, and there is a direct relationship between their order of elution and their isoelectric points. These data indicate that rapidly inducible PR3 expressed on the cell surface of PMN is an important bioactive form of the proteinase. If PR3 expression on the cell surface of PMN is dysregulated, it is well equipped to amplify tissue injury directly, and also indirectly via the generation of autoantibodies.

Quantum proteolysis by neutrophils: implications for pulmonary emphysema in alpha 1-antitrypsin deficiency.

Traditional enzyme kinetics provide a poor explanation for the increased risk of lung injury in alpha 1-antitrypsin (AAT) deficiency. Millimolar concentrations of leukocyte elastase, when released from single azurophil granules of activated neutrophils, lead to evanescent quantum bursts of proteolytic activity before catalysis is quenched by pericellular inhibitors. Herein, we tested the possibility that quantum proteolytic events are abnormal in AAT deficiency. We incubated neutrophils on opsonized fluoresceinated fibronectin in serum from individuals with various AAT phenotypes, and then measured and modeled quantum proteolytic events. The mean areas of the events in serum from heterozygous individuals (Pi MZ and Pi SZ) were slightly, but significantly, larger than those in serum from normal patients (Pi M). In marked contrast, mean areas of events in serum from AAT-deficient individuals were 10-fold larger than those in serum from normal patients. Diffusion modeling predicted that local elastase concentrations exceed AAT concentrations for less than 20 milliseconds and for more than 80 milliseconds in Pi M and Pi Z individuals, respectively. Thus, quantum proteolytic events are abnormally large and prolonged in AAT deficiency, leading directly to an increased risk of tissue injury in the immediate vicinity of activated neutrophils. These results have potentially important implications for the pathogenesis and prevention of lung disease in AAT deficiency.

Chromosomal organisation of a gene family encoding rhoptry proteins in Plasmodium yoelii.

The genomic organisation of the genes coding for a group of high molecular mass rhoptry proteins of the rodent malaria parasite Plasmodium yoelii YM was investigated using blotting, two dimensional gel electrophoresis and restriction fragment length analysis. The genes were found on chromosomes 1, 5, 6 and 10, with the possibility that related genes were also present on chromosomes 3 and 4. On chromosome 1 the genes were located close to one end, whereas they were present at both ends of chromosome 5, 6 and 10. Two genes, e3 and e8, that had been partially characterised previously were present on chromosomes 5 and 1, respectively. Based on an analysis of the 3' end of the genes, three subfamilies present on chromosomes 1, 5 and 6, and 10, respectively, were identified.

The cell biology of leukocyte-mediated proteolysis.

Leukocyte-derived proteinases have the capacity to degrade every component of the extracellular matrix, and thereby play fundamental roles in physiological processes. However, if the activity of these proteinases is uncontrolled or dysregulated, they have the capacity to contribute to tissue injury that potentially affects every organ in the body. Although there is a substantial literature on structure and activity of these proteinases when they are free in solution, until recently there has been little information about the cell biology of proteinases and their inhibitors. Recent studies, however, have identified several mechanisms by which inflammatory cells can degrade extracellular proteins in a milieu that contains high-affinity proteinase inhibitors.

Interaction between leukocyte elastase and elastin: quantitative and catalytic analyses.

Solubilization of elastin by human leukocyte elastase (HLE) cannot be analyzed by conventional kinetic methods because the biologically relevant substrate is insoluble and the concentration of enzyme-substrate complex has no physical meaning. We now report quantitative measurements of the binding and catalytic interaction between HLE and elastin permitted by analogy to receptor-ligand systems. Our results indicated that a limited and relatively constant number of enzyme binding sites were available on elastin, and that new sites became accessible as catalysis proceeded. The activation energies and solvent deuterium isotope effects were similar for catalysis of elastin and a soluble peptide substrate by HLE, yet the turnover number for HLE digestion of elastin was 200-2000-fold lower than that of HLE acting on soluble peptide substrates. Analysis of the binding of HLE to elastin at 0 degrees C, in the absence of significant catalytic activity, demonstrated two classes of binding sites (Kd=9.3x10(-9) M and 2.5x10(-7) M). The higher affinity sites accounted for only 6% of the total HLE binding capacity, but essentially all of the catalytic activity, and dissociation of HLE from these sites was minimal. Our studies suggest that interaction of HLE with elastin in vivo may be very persistent and permit progressive solubilization of this structurally important extracellular matrix component.

Leukocyte proteinases in wound healing: roles in physiologic and pathologic processes.

Leukocytes express a number of proteinases which play critical roles in physiologic processes during wound healing. However, if the activity of these proteinases is uncontrolled, they can contribute to devastating tissue injury that can affect most organ systems. Until recently, little was known about the mechanisms by which leukocytes retain the activity of their proteinases within the extracellular space which contains highly effective proteinase inhibitors. Studies of the cell biology of leukocyte proteinases have begun to identify the mechanisms by which proteinases can circumvent the effects of physiologic proteinase inhibitors. Herein, we will review the cell biology of leukocyte proteinases, and we will discuss the mechanisms by which leukocyte proteinases can contribute to physiologic processes occurring during wound healing, as well as their roles in pathologic processes.

Angiotensin II generation at the cell surface of activated neutrophils: novel cathepsin G-mediated catalytic activity that is resistant to inhibition.

Human neutrophils express inducible, catalytically active cathepsin G on their cell surface. Herein, we report that membrane-bound cathepsin G on intact neutrophils has potent angiotensin II-generating activity. Membrane-bound cathepsin G on activated neutrophils 1) converts both human angiotensin I and angiotensinogen to angiotensin II; 2) expresses angiotensin II-generating activity equivalent to 8.6 +/- 2.3 (+/-SD) x 10(-18) mol of free cathepsin G (5.2 +/- 1.4 x 10(6) molecules)/cell; and 3) has similar high affinity for angiotensin I compared with free cathepsin G (Km = 5.9 x 10(-4) and 4.6 x 10(-4) M; k(cat) = 4.0 and 2.0/s, respectively). In marked contrast to soluble cathepsin G, membrane-bound enzyme was substantially resistant to inhibition by plasma proteinase inhibitors and converted angiotensin I to angiotensin II even in undiluted plasma. There was a striking inverse relationship between inhibitor size and its effectiveness against membrane-bound cathepsin G activity. Alpha1-antichymotrypsin was a markedly ineffective inhibitor of membrane-bound enzyme (IC50 = 2.18 microM and 1.38 nM when tested against 1 nM membrane-bound and free cathepsin G, respectively). These data indicate that membrane-bound cathepsin G expressed on neutrophils is an inducible and mobile angiotensin II-generating system that may exert potent local vasoactive and chemoattractant properties at sites of inflammation.