Adaptation of the Banff Patellofemoral Instability Instrument (BPII) 2.0 into Swedish.

BACKGROUND AND PURPOSE: The Banff Patellofemoral Instability Instrument (BPII) 2.0 is a patient-reported outcome measure (PROM) designed specifically for patellofemoral instability. We translated and adapted the BPII 2.0 into Swedish and assessed its psychometric properties. PATIENTS AND METHODS: The BPII 2.0 was forward- and back-translated. Children aged 10-16 years with patellar dislocation and instability or recurrent dislocation were recruited. Children completed the Swedish BPII 2.0 and KOOS-Child during their initial visit (t0) and 1 week later (t1). Internal consistency and test-retest reliability were evaluated using intraclass correlation coefficients (ICCs) for the BPII 2.0 and KOOS-Child scores comparison. Pearson correlation coefficients examined concurrent validity of the Swedish BPII 2.0 subscales with KOOS-Child subscales. RESULTS: 64 children (46 females), mean age 13.8 (10.0-16.3) years, participated. Time after patellar dislocation or surgery was 3-24 months. 55 patients (86%) returned the second BPII 2.0 and KOOS-Child after an average of 9 (5-22) days. There were no ceiling or floor effects for the total score of the new Swedish BPII 2.0 or for its subscales. BPII 2.0 demonstrated excellent internal consistency at t0 (ICC 0.96, 95% confidence interval [CI] 0.95-0.97) and at t1 (ICC 0.97, CI 0.95-0.98), as well as excellent test-retest reliability (ICC 0.97, CI 0.96-0.98). Concurrent validity of the BPII 2.0 subscales with KOOS-Child subscales was moderate to strong (rho 0.40-0.88). CONCLUSION: The Swedish BPII 2.0 showed excellent internal consistency as well as excellent test-retest reliability and is a reliable and valid questionnaire.

Operative Repair of Medial Patellofemoral Ligament Injury Versus Knee Brace in Children With an Acute First-Time Traumatic Patellar Dislocation: A Randomized Controlled Trial.

BACKGROUND: A lateral patellar dislocation (LPD) is the most common traumatic knee injury with hemarthrosis in children. The redislocation rate is high. Varying operative and nonoperative treatments have been advocated with no consensus on the best treatment. PURPOSE: (1) To evaluate if arthroscopic-assisted repair of the medial patellofemoral ligament (MPFL) in patients with an acute first-time traumatic LPD would reduce the recurrence rate and offer better objective/subjective knee function compared with a knee brace without repair. (2) To study the presence of anatomic patellar instability risk factors (APIFs) and their association with a redislocation. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: This was a prospective series of 74 skeletally immature patients aged 9 to 14 years (38 girls and 36 boys; mean age, 13.1 years) with a first-time traumatic LPD, with clinical examinations, radiographs, magnetic resonance imaging, and diagnostic arthroscopic surgery performed within 2 weeks of the index injury. The child was randomized to either (1) a knee brace (KB group) for 4 weeks and physical therapy or (2) arthroscopic-assisted repair (R group) of the MPFL with anchors, 4 weeks with a soft cast splint, and physical therapy. The follow-up time was 2 years. RESULTS: The redislocation rate was significantly lower in the R group than in the KB group at final follow-up: 8 patients (22%) versus 16 patients (43%), respectively ( P = .047). The Knee injury and Osteoarthritis Outcome Score for children sport/play and quality of life subscales had lower scores in the R group compared with the KB group; the significant differences were among those with redislocations. The mean Kujala score was excellent in the KB group (95.9) and good in the R group (90.9). An impaired Limb Symmetry Index (median, 83%) for concentric quadriceps torque at 90 deg/s was found only in the R group. Eighty-one percent of the study patients had ≥2 APIFs. Trochlear dysplasia (trochlear depth <3 mm) had the highest odds ratio for redislocations (2.35 [95% CI, 0.69-8.03]), with no significant association between APIFs and a redislocation. CONCLUSION: Operative repair of an MPFL injury in the acute phase in skeletally immature children with a primary traumatic LPD significantly reduced the redislocation rate but did not improve subjective or objective knee function compared with a knee brace without repair. The majority of the patients in both groups were satisfied with their knee function. There was a high representation of APIFs, which needs to be considered when evaluating the risk of redislocations. Registration: ISRCTN 39959729 (Current Controlled Trials).

eNOS involved in colitis-induced mucosal blood flow increase.

The role of NO in inflammatory bowel disease is controversial. Studies indicate that endothelial nitric oxide synthase (eNOS) might be involved in protecting the mucosa against colonic inflammation. The aim of this study was to investigate the involvement of nitric oxide (NO) in regulating colonic mucosal blood flow in two different colitis models in rats. In anesthetized control and colitic rats, the distal colon was exteriorized and the mucosa visualized. Blood flow (laser-Doppler flowmetry) and arterial blood pressure were continuously monitored throughout the experiments, and vascular resistance was calculated. Trinitrobenzene sulfonic acid (TNBS) or dextran sulfate sodium (DSS) was used to induce colitis. All groups were given the NOS inhibitor N(omega)-nitro-l-arginine (l-NNA) or the inducible NOS (iNOS) inhibitor l-N(6)-(1-iminoethyl)-lysine (l-NIL). iNOS, eNOS, and neuronal NOS (nNOS) mRNA in colonic samples were investigated with real-time RT-PCR. Before NOS inhibition, colonic mucosal blood flow, expressed as perfusion units, was higher in both colitis models compared with the controls. The blood flow was reduced in the TNBS- and DSS-treated rats during l-NNA administration but was not altered in the control group. Vascular resistance increased more in the TNBS- and DSS-treated rats than in the control rats, indicating a higher level of vasodilating NO in the colitis models. l-NIL did not alter blood pressure or blood flow in any of the groups. iNOS and eNOS mRNA increased in both colitis models, whereas nNOS remained at the control level. TNBS- and DSS-induced colitis results in increased colonic mucosal blood flow, most probably due to increased eNOS activity.

Preoperative interleukin-6 production by mononuclear blood cells predicts survival after radical surgery for colorectal carcinoma.

BACKGROUND: Colorectal cancer is one of the most common forms of cancer in the Western world. Staging based on histopathology is currently the most accurate predictor of outcome after surgery. Colorectal cancer is curable if treated at an early stage (stage I-III). However, for tumors in stages II and III there is a great need for tests giving more accurate prognostic information defining the patient population in need of closer follow-up and/or adjuvant therapy. Furthermore, tests that provide prognostic information preoperatively could provide a guide both for preoperative oncologic treatment and the surgical procedure. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated preoperatively, within a week before primary surgery, from 39 patients undergoing surgery for colorectal cancer. The PBMCs were cultured in vitro for 24 hours in the presence of autologous serum and lipopolysaccharide (LPS). Interleukin-6 (IL-6) production was measured with enzyme-linked immunosorbent assay (ELISA). Staging based on histopathology was performed in all patients. Patients were followed for at least 54 months. RESULTS: A production of >5000 pg/mL of IL-6 identified colorectal cancer patients with a poor prognosis. Eight out of 13 patients with >5000 pg/mL IL-6 died from cancer within the follow-up period, whereas no cancer-related deaths were recorded among 21 patients with 5000 pg/mL IL-6 or less. A multivariate Cox regression analysis, stratified for T- and N-stage, identified IL-6 production as an independent prognostic factor. CONCLUSIONS: IL-6 production in vitro by PBMC can predict survival after radical surgery for colorectal cancer.

Cytocidal effects of atheromatous plaque components: the death zone revisited.

OBJECTIVE: Earlier we suggested that atheroma lesions constitute a "death zone" containing toxic materials that may cause dysfunction and demise of invading macrophages to prevent the removal of plaque materials. Here we have assessed the cytotoxic effects of nonfractionated gruel and insoluble (ceroid-like) material derived from advanced human atheroma. METHODS AND RESULTS: The insoluble material within advanced atherosclerotic plaque was isolated following protease K digestion and extensive extraction with aqueous and organic solvents. FTIR, Raman, and atomic absorption spectroscopy suggested that, despite its fluorescent nature, this material closely resembled hydroxyapatite and dentin, but also contained a significant amount of iron and calcium. When added to J774 cells and human macrophages in culture, this insoluble substance was phagocytosed, and progressive cell death followed. However, an even more cytotoxic activity was found in the atheromatous "gruel" that contains abundant carbonyls/aldehydes. Cell death caused by both crude gruel and ceroid could be blocked by preincubating cells with the lipophilic iron chelator salicylaldehyde isonicotinoyl hydrazone, apoferritin, BAPTA/AM, or sodium borohydride, indicating that cellular iron, calcium, and reactive aldehyde(s) are responsible for the observed cytotoxicity. CONCLUSIONS: Toxic materials within atheromatous lesions include both ceroid and even more cytotoxic lipidaceous materials. The cytotoxic effects of these plaque components may help explain the persistence of atherosclerotic lesions.

Foam cell death induced by 7beta-hydroxycholesterol is mediated by labile iron-driven oxidative injury: mechanisms underlying induction of ferritin in human atheroma.

Human atherosclerotic lesions typically contain large amounts of ferritin associated with apoptotic macrophages and foam cells, although the reasons are unknown. In the present investigation, we studied the relationship between ferritin induction and occurrence of apoptosis in 7beta-hydroxycholesterol (7beta-OH)-treated monocytic cells and macrophages. We found that 7beta-OH enlarges the intracellular labile iron pool, increases formation of reactive oxygen species (ROS), and induces ferritin and cytosolic accumulation of lipid droplets, lysosomal destabilization, and apoptototic macrophage death. Since ferritin is a phase II-type protective protein, our findings suggest that ferritin upregulation here worked as an inefficient defense mechanism. Addition to the culture medium of both a membrane-permeable iron chelator 10-phenanthroline and the non-membrane-permeable iron chelators apoferritin and desferrioxamine afforded significant protection against the 7beta-OH-induced effects. Consequently, endocytosed iron compounds dramatically augmented 7beta-OH-induced cytotoxicity. We conclude that oxidized lipid 7beta-OH causes not only foam cell formation but also oxidative damage with abnormal metabolism of cellular iron. The findings suggest that modulation of iron metabolism in human atheroma may be a potential therapeutic strategy against atherosclerosis.

Alpha-tocopherol and astaxanthin decrease macrophage infiltration, apoptosis and vulnerability in atheroma of hyperlipidaemic rabbits.

The composition of atherosclerotic plaques, not just macroscopical lesion size, has been implicated in their susceptibility to rupture and the risk of thrombus formation. By focusing on the quality of lipids, macrophages, apoptosis, collagen, metalloproteinase expression and plaque integrity, we evaluated the possible anti-atherosclerotic effect of the antioxidants alpha-tocopherol and astaxanthin in Watanabe heritable hyperlipidemic (WHHL) rabbits. Thirty-one WHHL rabbits were divided into three groups and were fed a standard diet, as controls (N =10), or a standard diet with the addition of 500 mg alpha-tocopherol per kg feed (N =11) or 100 mg astaxanthin per kg feed (N =10) for 24 weeks. We found that both antioxidants, particularly astaxanthin, significantly decreased macrophage infiltration in the plaques although they did not affect lipid accumulation. All lesions in the astaxanthin-treated rabbits were classified as early plaques according to the distribution of collagen and smooth muscle cells. Both antioxidants also improved plaque stability and significantly diminished apoptosis, which mainly occurred in macrophages, matrix metalloproteinase three expressions and plaque ruptures. Although neither antioxidant altered the positive correlations between the lesion size and lipid accumulation, the lesion size and apoptosis were only positively correlated in the control group. Astaxanthin and alpha-tocopherol may improve plaque stability by decreasing macrophage infiltration and apoptosis in this atherosclerotic setting. Apoptosis reduction by alpha-tocopherol and astaxanthin may be a new anti-atherogenic property of these antioxidants.

Enhanced expression of natural resistance-associated macrophage protein 1 in atherosclerotic lesions may be associated with oxidized lipid-induced apoptosis.

The natural resistance-associated macrophage proteins (Nramps) can modulate inflammatory reactions. Nramps are not only responsible for intracellular divalent metal transport but also determine the macrophage functions in inflammatory processes. In the present study we tested whether Nramp1 is involved in macrophage apoptosis induced by oxidized lipids in atherogenesis. Arterial segments of Watanabe heritable hyperlipidemic rabbits were used for an examination of Nramp1 mRNA by in situ RT-PCR and macrophage immunohistochemistry. Annexin V/PI staining and terminal dUTP nick-end labeling (TUNEL) techniques were used for apoptosis detection. We found that, in macrophage-rich areas (positive to RMA-11) of the rabbit atherosclerotic aorta, there were lesion-dependent increases in Nramp1 mRNA, which are mainly apoptotic foamy macrophages that are positive to TUNEL staining. U937 cells were treated with 7beta-hydroxycholesterol (7beta-OH) in the presence or absence of the redox-active iron chelator desferrioxamine (DFO) or 1,10-phenanthroline. The cellular iron chelators considerably reduced, whereas iron compounds enhanced, 7beta-OH-induced apoptosis and necrosis. DFO also decreased mRNA levels of Nramp1, whereas both iron compounds and 7beta-OH dramatically enhanced the expression of Nramp1 mRNA, particularly among 7beta-OH-induced apoptotic cells. We conclude that the enhanced expression of Nramp1 in macrophage regions of atherosclerotic lesions may be associated with ferrous iron-enhanced, oxidized lipid-induced apoptosis. This finding reveals a novel function of Nramp1 in atherogenesis.