Inflammation and post-operative recovery in patients undergoing total knee arthroplasty-secondary analysis of a randomized controlled trial.

OBJECTIVE: Reduced function persists for many patients after total knee arthroplasty (TKA). Inflammation is part of osteoarthritis' pathophysiology, and surgery induces a marked inflammatory response. We therefore wanted to explore the role of inflammation in long-term recovery after TKA, and thus conducted this secondary analysis of our randomized controlled trial (RCT) of physical rehabilitation ± progressive strength training (PST). We aimed to investigate whether (1) inflammation is associated with functional performance, knee-extension strength, and knee pain before TKA; (2) PST affects inflammation, and the inflammatory state over time; (3) baseline or surgery-induced inflammation modifies the effect of rehabilitation ± PST on change in 6-min walk test (Δ6MWT); and (4) baseline or surgery-induced inflammation is associated with Δ6MWT following TKA. DESIGN: In the primary trial report's per-protocol analysis, 72/82 patients were included. Sixty had ≥1 blood sample before and after TKA, and were included in this secondary analysis. Inflammation was measured by interferon γ-inducible protein (IP)-10, soluble urokinase plasminogen activator receptor (suPAR), interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α at baseline; day 1, week 4, 8, and 26 after TKA. RESULTS: At baseline, suPAR (P = 006) was negatively associated with 6MWT. Neither baseline nor surgery-induced inflammation modified the response to rehabilitation ± PST. Only surgery-induced IL-10 was associated with Δ6MWT26 weeks-baseline (P = 0.001), also adjusted for 6MWTbaseline, age, sex and body mass index (BMI). CONCLUSION: In this secondary analysis, only increased surgery-induced IL-10 response was associated with decreased long-term functional performance after TKA. The importance of controlling the surgery-induced immune response remains to be investigated further. TRIAL IDENTIFICATION: NCT01351831.

High Re-Operation Rates Using Conserve Metal-On-Metal Total Hip Articulations.

INTRODUCTION: Metal-on-metal hip articulations have been intensely debated after reports of adverse reactions and high failure rates. The aim of this study was to retrospectively evaluate the implant of a metal-on.metal total hip articulation (MOM THA) from a single manufacture in a two-center study. MATERIALS AND METHODS: 108 CONSERVE(®) MOM THA were implanted in 92 patients between November 2005 and December 2010. Patients had at time of retrospective evaluation their journals reviewed for re-operations and adverse reactions. RESULTS: 20 hips were re-operated (18.4%) at a mean follow up of 53 months. 4 pseudotumors were diagnosed at time of follow up but no substantiated link was made between adverse reactions and re-operations. CONCLUSION: The high re-operation rates found in this study raised concern about the usage of the MOM THA and subsequently lead to the termination of implantation of this MOM THA at the two orthopaedic departments.

Routine noninvasive prenatal screening for fetal RHD in plasma of RhD-negative pregnant women-2 years of screening experience from Denmark.

OBJECTIVE: Prenatal and postnatal RhD prophylaxis reduces the risk of RhD immunization in pregnancies of RhD-negative women. Based on the result from prenatal screening for the fetal RHD gene, prenatal RhD prophylaxis in Denmark is targeted to RhD-negative women who carry an RhD-positive fetus. Here, we present a 2-year evaluation of a nationwide prenatal RHD screening. METHODS: Blood samples were drawn from RhD-negative women in gestational week 25. DNA was extracted from maternal plasma and analyzed for the RHD gene. The prenatal RHD results were compared with the serological typing of newborns in 12,668 pregnancies. Early compliance was assessed for 690 pregnancies. RESULTS: The sensitivity for the detection of fetal RHD was 99.9% (95% CI: 99.7-99.9%). Unnecessary recommendation of prenatal RhD prophylaxis was avoided in 97.3% of the women carrying an RhD-negative fetus. Fetuses that were seropositive for RhD were not detected in 11 pregnancies (0.087%). The sample uptake percentage was 84.2%, and the compliance for prenatal anti-D administration was 93.2%. CONCLUSION: The high sensitivity, maintained over 2 years, underlines the reliability of routine prenatal fetal RHD screening in RhD-negative pregnant women, specifically at 25 weeks of gestation. The remaining challenges are logistical and are related to program compliance.

No positive effect of Acid etching or plasma cleaning on osseointegration of titanium implants in a canine femoral condyle press-fit model.

PURPOSE: Implant surface treatments that improve early osseointegration may prove useful in long-term survival of uncemented implants. We investigated Acid Etching and Plasma Cleaning on titanium implants. METHODS: In a randomized, paired animal study, four porous coated Ti implants were inserted into the femurs of each of ten dogs. PC (Porous Coating; control)PC+PSHA (Plasma Sprayed Hydroxyapatite; positive control)PC+ET (Acid Etch)PC+ET+PLCN (Plasma Cleaning) After four weeks mechanical fixation was evaluated by push-out test and osseointegration by histomorphometry. RESULTS: The PSHA-coated implants were better osseointegrated than the three other groups on outer surface implant porosity (p<0.05) while there was no statistical difference in deep surface implant porosity when compared with nontreated implant. Within the deep surface implant porosity, there was more newly formed bone in the control group compared to the ET and ET+PCLN groups (p<0.05). In all compared groups, there was no statistical difference in any biomechanical parameter. CONCLUSIONS: In terms of osseointegration on outer surface implant porosity PC+PSHA was superior to the other three groups. Neither the acid etching nor the plasma cleaning offered any advantage in terms of implant osseointegration. There was no statistical difference in any of the biomechanical parameters among all groups in the press-fit model at 4 weeks of evaluation time.

Heavy metals, PAHs and toxicity in stormwater wet detention ponds.

Concentrations of 6 different heavy metals and total polycyclic aromatic hydrocarbons (PAHs) were determined in stormwater runoff and in the pond water of two Danish wet detention ponds. The pond water samples were analyzed for toxic effects, using the algae Selenastrum capricornutum as a test organism. Stormwater and pond water from a catchment with light industry showed high levels of heavy metals, especially zinc and copper. The pond water showed high toxic effects and copper were found to be the main toxicant. Additionally, a large part of the copper was suspected to be complex bound, reducing the potential toxicity of the metal. Another catchment (residential) produced stormwater and pond water with moderate concentration of heavy metals. The pond water occasionally showed toxic effects but no correlation between heavy metals and toxicity was identified. PAHs concentrations were for both catchments low and no correlations between PAH concentrations in the pond and toxicity were found.

Reduced midbrain-pons serotonin transporter binding in patients with obsessive-compulsive disorder.

OBJECTIVE: To evaluate current hypothesis regarding the pathophysiology of obsessive-compulsive disorder (OCD) by studying the serotonin receptor binding in patients with OCD using single photon emission computerized tomography (SPECT). METHOD: We studied nine patients (four men and five women, age range 21-56 years) fulfilling the DMS-III-R criteria for OCD using SPECT and the serotonin transporter (SERT) tracer (123)I-beta-CIT. SERT binding potential (BP2) was determined by Logan plot derived from seven scans obtained during 10-400 min. RESULTS: The binding of (123)I-beta-CIT in midbrain-pons was reduced in OCD patients when compared with controls (BP2 0.97 +/- 0.07 vs. 0.84 +/- 0.12, P = 0.011). There was no correlation between BP2 and any of the clinical variables (age at onset, disease duration, and Yale-Brown Obsessive-Compulsive Scale score). CONCLUSION: This study suggests a reduced serotonergic input into the fronto-subcortical circuits in OCD, thereby diminishing the inhibitory regulation of serotonin on these circuits.

Use of optical scatter sensors for measurement of visibility.

A study on the measurement of visibility by the use of light scattering has been carried out. The basis for the research was the optical forward-scatter sensor, Mira visibility sensor, developed and produced by Aanderaa Instruments. The focus of the study was on how to measure correct visibility at different weather situations (e.g. fog, rain, haze and snow) and how a sensor can provide information on the type of particles/drops which are causing reduced visibility. Optical scatter measurement of airborne dust was also investigated. The work includes theoretical calculations and experimental work. The correlations between scatter measurements and both visibility and the concentration of airborne dust are studied. A short introduction to the subject of visibility measurement is also included.

The ADP ribosyltransferase domain of Pseudomonas aeruginosa ExoT contributes to its biological activities.

ExoT is a type III secreted effector protein found in almost all strains of Pseudomonas aeruginosa and is required for full virulence in an animal model of acute pneumonia. It is comprised of an N-terminal domain with GTPase activating protein (GAP) activity towards Rho family GTPases and a C-terminal ADP ribosyltransferase (ADPRT) domain with minimal activity towards a synthetic substrate in vitro. Consistent with its activity as a Rho family GTPase, ExoT has been shown to inhibit P. aeruginosa internalization into epithelial cells and macrophages, disrupt the actin cytoskeleton through a Rho-dependent pathway, and inhibit wound repair in a scrape model of injured epithelium. We have previously shown that mutation of the invariant arginine of the GAP domain to lysine (R149K) results in complete loss of GAP activity in vitro but only partially inhibits ExoT anti-internalization and cell rounding activity. We have constructed in-frame deletions and point mutations within the ADPRT domain in order to test whether this domain might account for the residual activity observed in ExoT GAP mutants. Deletion of a majority of the ADPRT domain (residues 234 to 438) or point mutations of the ADPRT catalytic site (residues 383 to 385) led to distinct changes in host cell morphology and substantially reduced the ability of ExoT to inhibit in vitro epithelial wound healing over a 24-h period. In contrast, only subtle effects on the efficiency of ExoT-induced bacterial internalization were observed in the ADPRT mutant forms. Expression of each domain individually in Saccharomyces cerevisiae was toxic, whereas expression of each of the catalytically inactive mutant domains was not. Collectively, these data demonstrate that the ADPRT domain of ExoT is active in vivo and contributes to the pathogenesis of P. aeruginosa infections.

[Therapeutic changes beyond the symptoms - effects of inpatient treatment according to the Heidelberg Structural Change Scale]. / Therapeutische Veränderungen jenseits der Symptomatik - Wirkungen stationärer Psychotherapie im Licht der Heidelberger Umstrukturierungsskala.

The question is discussed how changes concerning the patient's ability to recognize and obtain insight into dysfunctional relationship patterns, life-determining conflicts, and structural vulnerability as well as the readiness to take on the responsibility for the negative effects caused by these may be conceptualized. A model has been developed based on Operationalized Psychodynamic Diagnosis (OPD) in which individual problem areas for each patient may be chosen from a list of foci. Changes in these foci are evaluated using the Heidelberg Structural Change Scale which is presented and discussed in detail. This concept is applied to a sample of patients who had been treated in an in-patient setting. It is demonstrated that this method of measuring changes can be used reliably. Furthermore, the changes registered with the structural change scale correlate on an absolute level quite high to the global assessment of outcome through the therapeutic team; this correlation is even higher than the correlation between symptomatic changes and the global assessments. How this concept may be applied in planning, evaluating, and ensuring the quality of psychotherapy is presented in conclusion.

Enhanced cleavage of RNA mediated by an interaction between substrates and the arginine-rich domain of E. coli ribonuclease E.

Endonucleolytic cutting by the essential Escherichia coli ribonuclease RNaseE has a central role in both the processing and decay of RNA. Previously, it has been shown that an oligoribonucleotide corresponding in sequence to the single-stranded region at the 5' end of RNAI, the antisense regulator of ColE1-type plasmid replication, is efficiently cut by RNaseE. Combined with the knowledge that alteration of the structure of stem-loops within complex RNaseE substrates can either increase or decrease the rate of cleavage, this result has led to the notion that stem-loops do not serve as essential recognition motifs for RNaseE, but can affect the rate of cleavage indirectly by, for example, determining the single-strandedness of the site or its accessibility. We report here, however, that not all oligoribonucleotides corresponding to RNaseE-cleaved segments of complex substrates are sufficient to direct efficient RNaseE cleavage. We provide evidence using 9 S RNA, a precursor of 5 S rRNA, that binding of structured regions by the arginine-rich RNA- binding domain (ARRBD) of RNaseE can be required for efficient cleavage. Binding by the ARRBD appears to counteract the inhibitory effects of sub-optimal cleavage site sequence and overall substrate conformation. Furthermore, combined with the results from recent analyses of E. coli mutants in which the ARRBD of RNase E is deleted, our findings suggest that substrate binding by RNaseE is essential for the normal rapid decay of E. coli mRNA. The simplest interpretation of our results is that the ARRBD recruits RNaseE to structured RNAs, thereby increasing the localised concentration of the N-terminal catalytic domain, which in turn leads to an increase in the rate of cleavage.

[Prevalence of left ventricular hypertrophy in Danish patients with hypertension]. / Forekomsten af venstresidig hjertehypertrofi hos danske personer med hypertension.

The aim of this investigation was to study the prevalence of left ventricular hypertrophy (LVH) in a hypertensive population with reference to a normotensive control group. From the general population, 3498 men and women aged 35, 45, 55 and 65 years old were invited to a health examination. Participants with blood pressure above 160 mmHg systolic and/or 95 mmHg diastolic or participants currently taking antihypertensive medication or having done so during the previous six months were asked to undergo an echocardiographic examination. Controls were randomly selected from the same population. Of 552 participants in the final study population, 194 were normotensive controls and 358 were in the hypertensive group. Echocardiographic measurements were made according to the "Penn" conventions and indexed for body surface. Cutoff values for LVH were 134 grams per m2 for males and 102 grams per m2 for women. Overall, we found that the prevalence of 1 VH was 14%/20% (men/women) in normotensives and 25%/26% in hypertensives (p < 0.01). By subdivision in age and sex groups we found that the relation between normotensives and hypertensives was significant in the age group of 65 years (p < 0.02 for males and p < 0.05 for females). The association between blood pressure and 1 VH in the general population is weak. 1 VH is only significantly more frequent among hypertensives as compared to normotensives in older people.

Prevalence of left ventricular hypertrophy in a hypertensive population.

AIMS: This investigation was set up to study the prevalence of left ventricular hypertrophy in a hypertensive population with reference to a normotensive control group. From the general population 3498 men and women aged 35, 45, 55 and 65 years old were invited to a health examination. Participants with blood pressure above 160 mmHg systolic or 95 mmHg diastolic or those taking antihypertensive medication or having done so during the previous 6 months were asked to undergo an echocardiographic examination. Normotensive controls were randomly selected from the same population. Of 552 participants in the final study population, 194 were normotensive controls and 358 were in the hypertensive group. Echocardiographic measurements were made according to the Penn conventions and indexed for body surface. Cut-off values for left ventricular hypertrophy were 134 g.m-2 for males and 102 g.m-2 for women. RESULTS: Overall, the prevalence of left ventricular hypertrophy was 14%/20% (men/women) in normotensives and 25%/26% in hypertensives (P < 0.01). After subdivision by age and sex, there was a significant difference in the prevalence of left ventricular hypertrophy between normotensives and hypertensives only in the 65-year-old group (P < 0.02 for males and P < 0.05 for females). CONCLUSIONS: The association between blood pressure and left ventricular hypertrophy in the general population is weak. Left ventricular hypertrophy is only significantly more frequent among hypertensives as compared to normotensives in older people.

Effect of dietary coenzyme Q10 as an antioxidant in human plasma.

A human study including 22 volunteers was conducted to investigate the antioxidative effect in blood of dietary coenzyme Q10 supplementation. The levels of alpha-tocopherol, ascorbic acid, lipid peroxidation (measured as TBARS) and the redox status of CoQ10 (reduced CoQ10/total CoQ10) were measured in plasma as markers for the antioxidative status once a week during the study period. To introduce an increased oxidative stress, a fish oil supplementation was given. The levels of alpha-tocopherol and ascorbic acid and the redox status did not change upon CoQ10 supplementation, while the level of TBARS decreased. The decrease in TBARS might be ascribed to an antioxidative effect of the supplied CoQ10. The constant redox level of CoQ10 during the CoQ10 supplementation shows that the exogenous CoQ10 is reduced during absorption and subsequent incorporation into lipoproteins, which is a prerequisite for its antioxidative function. The fish oil supplementation resulted in a higher TBARS level and a lower alpha-tocopherol level, but the redox level of CoQ10 was unchanged. In conclusion, the CoQ10 supplementation resulted in a higher plasma level of reduced CoQ10 and a lower TBARS level, but sparing of other plasma antioxidants (i.e. ascorbic acid and alpha-tocopherol) was not observed.

Antioxidative effect of dietary coenzyme Q10 in human blood plasma.

The effect of an oral dose of 90 mg/day coenzyme Q10 on the antioxidative status in 22 healthy young subjects (9 men and 13 women) was investigated before and after induction of an oxidative stress by fish oil supplementation. The levels of oxidised and reduced coenzyme Q10, alpha-tocopherol, ascorbate, TBARS and the fatty acid composition of phospholipids were determined in plasma. The total amount of plasma coenzyme Q10 increased significantly from 0.7 +/- 0.1 mumol/l before supplementation to 1.7 +/- 0.3 mumol/l after one week of supplementation while the redox status (reduced CoQ10/total CoQ10) remained constant, even during a following fish oil supplementation. The level of TBARS decreased during the first 2 weeks of CoQ10 ingestion while the content of alpha-tocopherol increased in the second week and ascorbate did not change. The decrease of TBARS and the presence of the majority of the orally supplemented CoQ10 in the reduced form in plasma seem to indicate an antioxidative role of CoQ10 in blood plasma.

[Colchicine treatment of recurrent steroid-dependent pericarditis in a patient with post-myocardial-infarction syndrome (Dressler's syndrome)]. / Kolkicinbehandling af recidiverende "steroidafhaengig" pericarditis hos en patient med postmyokardieinfarktsyndrom (Dressler's syndrom).

The usual treatment of pericarditis consists of non-steroid anti-inflammatory agents. In cases where the symptoms and/or the pericardial effusion persist or progress, the disease can be arrested in the majority of cases by employing steroids. In some patients, it may prove difficult to conclude steroid treatment as gradual withdrawal results in recurrence and it may, therefore, be necessary to continue with large doses of steroid for prolonged periods. There is, however, a possibility for another form of treatment. The present authors present the case history of a patient with pericarditis on the basis of the post-myocardial-infarction syndrome and in whom the symptoms recurred several times during attempts at gradual withdrawal of prednisolone. Treatment with colchicine was commenced. The patient rapidly became symptom free and has now been symptom free for 45 weeks without prednisolone. Colchicine was withdrawn after 33 weeks without recurrence. It is considered that trial of colchicine treatment can be recommended in cases of recurring pericarditis particularly when there are problems (recurrence) on attempted withdrawal of steroid treatment. Naturally, it is important to exclude specific causes requiring other forms of treatment as the cause of the pericarditis (e.g. malignant disease, tuberculosis, systemic disease etc.).

[Should athletic injuries be treated with non-steroidal anti-rheumatic agents (NSAID)? Tenoxicam, piroxicam and placebo in the treatment of acute stress-induced injuries]. / Skal sportsskader behandles med ikke-steroide antireumatika (NSAID)? Tenoxicam, piroxicam og placebo ved behandling af akutte belastningsinducerede skader.

A total of 212 patients with acute sports injuries were allotted at random to treatment with 20 mg tenoxicam daily, 20 piroxicam daily or a placebo for ten days. The injuries could be subdivided into six groups: Tendinitis, periostitis, sprains, tendovaginitis, epicondylitis and muscular ruptures. Treatment was well tolerated and analysis of the total material showed a slight but significantly better effect in the group treated with the active drugs. More detailed analysis revealed that this increased effect was produced by a definitely better therapeutic result in the group of patients with tendinitis treated with non-steroid anti-inflammatory drugs (NSAID) while, in the other types of injury, no definite effect could be observed. On the basis of these observations, the authors conclude that acute tendinitis may be treated with NSAID (tenoxicam) while the question is not yet solved where other acute stress-induced injuries are concerned.

[Fatal septicemia caused by Salmonella dublin]. / Septikaemi forårsaget af Salmonella dublin med letalt forløb.

A case of Salmonella Dublin infection which ran a lethal course in a woman aged 49 years is described. Salmonella Dublin was first isolated in Denmark in recent years and appears to be associated with more serious clinical pictures than the other zoonotic Salmonella serotypes. The incidence of S. Dublin is increasing particularly in France and Belgium. It was first isolated from human cases in Denmark in recent years. In the clinical microbiological department in the County of Copenhagen, S. Dublin constitutes approximately 1% of the zoonotic Salmonella serotypes which are isolated from faeces while it is one of the commonest Salmonella serotypes isolated from blood.