Feedforward contraction of transversus abdominis is not influenced by the direction of arm movement

Because the structure of the spine is inherently unstable, muscle activation is essential for the maintenance of trunk posture and intervertebral control when the limbs are moved. To investigate how the central nervous system deals with this situation the temporal components of the response of the muscles of the trunk were evaluated during rapid limb movement performed in response to a visual stimulus. Fine-wire electromyography (EMG) electrodes were inserted into transversus abdominis (TrA), obliquus internus abdominis (OI) and obliquus externus abdominis (OE) of 15 subjects under the guidance of real-time ultrasound imaging. Surface electrodes were placed over rectus abdominis (RA), lumbar multifidus (MF) and the three parts of deltoid. In a standing position, ten repetitions of shoulder flexion, abduction and extension were performed by the subjects as fast as possible in response to a visual stimulus. The onset of TrA EMG occurred in advance of deltoid irrespective of the movement direction. The time to onset of EMC activity of OI, OE, RA and MF varied with the movement direction, being activated earliest when the prime action of the muscle opposed the reactive forces associated with the specific limb movement. It is postulated that the non-direction-specific contraction of TrA may be related to the control of trunk. stability independent of the requirement for direction-specific control of the centre of gravity in relation to the base of support.

Depression: a predictor of smoking relapse in a 6-month follow-up after hospitalization for acute coronary syndrome

Objective The objective of the study was to investigate whether depression is a predictor of postdischarge smoking relapse among patients hospitalized for myocardial infarction (MI) or unstable angina (ILIA), in a smoke-free hospital. Methods Current smokers with MI or UA were interviewed while hospitalized; patients classified with major depression (MD) or no humor disorder were reinterviewed 6 months post discharge to ascertain smoking status. Potential predictors of relapse (depression; stress; anxiety; heart disease risk perception; coffee and alcohol consumption; sociodemographic, clinical, and smoking habit characteristics) were compared between those with MD (n = 268) and no humor disorder (n = 135). Results Relapsers (40.4%) were more frequently and more severely depressed, had higher anxiety and lower self-efficacy scale scores, diagnosis of UA, shorter hospitalizations, started smoking younger, made fewer attempts to quit, had a consort less often, and were more frequently at the `precontemplation` stage of change. Multivariate analysis showed relapse-positive predictors to be MD [odds ratio (OR): 2.549; 95% confidence interval (CI): 1.519-4.275] (P<0.001); `precontemplation` stage of change (OR: 7.798; 95% CI: 2.442-24.898) (P<0.001); previous coronary bypass graft surgery (OR: 4.062; 95% CI: 1.356-12.169) (P=0.012); and previous anxiolytic use (OR: 2.365; 95% CI: 1.095-5.107) (P=0.028). Negative predictors were diagnosis of MI (OR: 0.575; 95% CI: 0.361-0.916) (P=0.019); duration of hospitalization (OR: 0.935; 95% CI: 0.898-0.973) (P=0.001); smoking onset age (OR: 0.952; 95% CI: 0.910-0.994) (P=0.028); number of attempts to quit smoking (OR: 0.808; 95% CI: 0.678-0.964) (P=0.018); and `action` stage of change (OR: 0.065; 95% CI: 0.008-0.532) (P= 0.010). Conclusion Depression, no motivation, shorter hospitalization, and severity of illness contributed to postdischarge resumption of smoking by patients with acute coronary syndrome, who underwent hospital-initiated smoking cessation.

Pentoxifylline reduces pro-inflammatory and increases anti-inflammatory activity in patients with coronary artery disease - A randomized placebo-controlled study

The balance between different immunological stimuli is essential in the progression and stabilization of atherosclerotic plaques. Immune regulation has been suggested as potential target for the treatment of atherosclerotic disease. We sought to determine whether treatment with pentoxifylline, a phosphodiesterase inhibitor with immunomodulating properties, could reduce the pro-inflammatory response observed in patients with acute coronary syndromes (ACS) and increase anti-inflammatory activity. In a double-blind, prospective, placebo-controlled study, 64 patients with ACS were randomized to receive pentoxifylline 400 mg TID or placebo for 6 months. Analysis of the pro-inflammatory markers, Greactive protein (CRP), interleukin (IL)-6, IL-12, interferon-gamma and tumor necrosis factor (TNF)-alpha and the anti-inflammatory cytokines, transforming growth factor (TGF)-beta 1 and IL-10 were done at baseline, 1 and 6 months. Pentoxifylline treatment significantly reduced the adjusted levels of CRP and TNF-alpha compared to placebo after 6 months (P=0.04 and P < 0.01, respectively). IL-12 increase was significantly less pronounced with pentoxifylline (P=0.04). The levels of the anti-inflammatory cytokine, IL-10, also declined significantly less in the pentoxifylline group compared to placebo (P < 0.01) with a trend towards a higher increase of TGF-beta 1 in the former group (P=0.16). Pentoxifylline reduces pro-inflammatory and increases anti-inflammatory response in patients with ACS and may have beneficial clinical effects on cardiovascular events. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

Effect of the Novel Thienopyridine Prasugrel Compared With Clopidogrel on Spontaneous and Procedural Myocardial Infarction in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38 An Application of the Classification System From the Universal Definition of Myocardial Infarction

Background-Prasugrel is a novel thienopyridine that reduces new or recurrent myocardial infarctions (MIs) compared with clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention. This effect must be balanced against an increased bleeding risk. We aimed to characterize the effect of prasugrel with respect to the type, size, and timing of MI using the universal classification of MI. Methods and Results-We studied 13 608 patients with acute coronary syndrome undergoing percutaneous coronary intervention randomized to prasugrel or clopidogrel and treated for 6 to 15 months in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction (TRITON-TIMI 38). Each MI underwent supplemental classification as spontaneous, secondary, or sudden cardiac death (types 1, 2, and 3) or procedure related (Types 4 and 5) and examined events occurring early and after 30 days. Prasugrel significantly reduced the overall risk of MI (7.4% versus 9.7%; hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.67 to 0.85; P < 0.0001). This benefit was present for procedure-related MIs (4.9% versus 6.4%; HR, 0.76; 95% CI, 0.66 to 0.88; P = 0.0002) and nonprocedural (type 1, 2, or 3) MIs (2.8% versus 3.7%; HR, 0.72; 95% CI, 0.59 to 0.88; P = 0.0013) and consistently across MI size, including MIs with a biomarker peak >= 5 times the reference limit (HR. 0.74; 95% CI, 0.64 to 0.86; P = 0.0001). In landmark analyses starting at 30 days, patients treated with prasugrel had a lower risk of any MI (2.9% versus 3.7%; HR, 0.77; P = 0.014), including nonprocedural MI (2.3% versus 3.1%; HR, 0.74; 95% CI, 0.60 to 0.92; P = 0.0069). Conclusion-Treatment with prasugrel compared with clopidogrel for up to 15 months in patients with acute coronary syndrome undergoing percutaneous coronary intervention significantly reduces the risk of MIs that are procedure related and spontaneous and those that are small and large, including new MIs occurring during maintenance therapy. (Circulation. 2009; 119: 2758-2764.)

Continuous positive airway pressure increases inspiratory capacity of COPD patients

Background and objective: Hyperinflation with a decrease in inspiratory capacity (IC) is a common presentation for both unstable and stable COPD patients. As CPAP can reduce inspiratory load, possibly secondary to a reduction in hyperinflation, this study examined whether CPAP would increase IC in stable COPD patients. Methods: Twenty-one stable COPD patients (nine emphysema, 12 chronic bronchitis) received a trial of CPAP for 5 min at 4, 7 and 11 cmH(2)O. Fast and slow VC (SVC) were measured before and after each CPAP trial. In patients in whom all three CPAP levels resulted in a decreased IC, an additional trial of CPAP at 2 cmH(2)O was conducted. For each patient, a `best CPAP` level was defined as the one associated with the greatest IC. This pressure was then applied for an additional 10 min followed by spirometry. Results: Following application of the `best CPAP`, the IC and SVC increased in 15 patients (nine emphysema, six chronic bronchitis). The mean change in IC was 159 mL (95% CI: 80-237 mL) and the mean change in SVC was 240 mL (95% CI: 97-386 mL). Among these patients, those with emphysema demonstrated a mean increase in IC of 216 mL (95% CI: 94-337 mL). Six patients (all with chronic bronchitis) did not demonstrate any improvement in IC. Conclusions: The best individualized CPAP can increase inspiratory capacity in patients with stable COPD, especially in those with emphysema.

Endostatin- and interleukin-2-expressing retroviral bicistronic vector for gene therapy of metastatic renal cell carcinoma

Background Metastatic renal cell carcinoma (mRCC) is one of the most treatment-resistant malignancies. Despite all new therapeutic advances, almost all patients develop resistance to treatment and cure is rarely seen. In the present study, we evaluated the antitumor effect of a bicistronic retrovirus vector encoding both endostatin (ES) and interleukin (IL)-2 using an orthotopic metastatic RCC mouse model. Methods Balb/C-bearing Renca cells were treated with NIH/3T3-LendIRES-IL-2-SN cells. In the survival studies, mice were monitored daily until they died. At the end of the in vivo experiment, serum levels of IL-2 and ES were measured, the lung was weighed, and the number of metastatic nodules, nodule area, tumor vessels and proliferation of tumor-infiltrating Renca cells were determined. Results Inoculation of NIH/3T3-LendIRES-IL-2-SN cells resulted in an increase in ES and IL-2 levels in the treated group (p < 0.05). There was a significant decrease in lung wet weight, lung nodule area and tumor vessels in the treated group compared to the control group (p < 0.001). The proliferation of Renca cells in the bicistronic-treated group was significantly reduced compared to the control group (p < 0.05). Kaplan-Meier survival curves showed that the probability of survival was significantly higher for mice submitted to bicistronic therapy (log-rank test, p = 0.0016). Bicistronic therapy caused an increase in the infiltration of CD4, CD4 interferon (IFN)gamma-producing, CD8, CD8 IFN gamma-producing and natural killer (CD49b) cells. Conclusions Retroviral bicistronic gene transfer led to the secretion of functional ES and IL-2 that was sufficiently active to: (i) inhibit tumor angiogenesis and tumor cell proliferation and (ii) increase the infiltration of immune cells (C) Copyright. 2011 John Wiley & Sons, Ltd.

Endostatin gene therapy enhances the efficacy of IL-2 in suppressing metastatic renal cell carcinoma in mice

We investigated whether the administration of IL-2 combined with endostatin gene therapy was able to produce additive or even synergistic immunomodulatory activity in a mouse model of metastatic renal carcinoma. Renca cells were injected into the tail vein of BALB/c mice. After 24 h, the animals were randomly divided into four groups (5 mice/group). One group of mice was the control, the second group received treatment with 100,000 UI of Recombinant IL-2 (Proleukin, Chiron) twice a day, 1 day per week during 2 weeks (IL-2), the third group received treatment with a subcutaneous inoculation of 3.6 x 10(6) endostatin-producing cells, and the fourth group received both therapies (IL-2 + ES). Mice were treated for 2 weeks. In the survival studies, 10 mice/group daily, mice were monitored daily until they died. The presence of metastases led to a twofold increase in endostatin levels. Subcutaneous inoculation of NIH/3T3-LendSN cells resulted in a 2.75 and 2.78-fold increase in endostatin levels in the ES and IL-2 + ES group, respectively. At the end of the study, there was a significant decrease in lung wet weight, lung nodules area, and microvascular area (MVA) in all treated groups compared with the control group (P < 0.001). The significant difference in lung wet weight and lung nodules area between groups IL-2 and IL-2 + ES revealed a synergistic antitumor effect of the combined treatment (P < 0.05). The IL-2 + ES therapy Kaplan-Meier survival curves showed that the probability of survival was significantly higher for mice treated with the combined therapy (log-rank test, P = 0.0028). Conjugated therapy caused an increase in the infiltration of CD4, CD8 and CD49b lymphocytes. An increase in the amount of CD8 cells (P < 0.01) was observed when animals received both ES and IL-2, suggesting an additive effect of ES over IL-2 treatment. A synergistic effect of ES on the infiltration of CD4 (P < 0.001) and CD49b cells (P < 0.01) was also observed over the effect of IL-2. Here, we show that ES led to an increase in CD4 T helper cells as well as cytotoxic lymphocytes, such as NK cells and CD8 cells, within tumors of IL-2 treated mice. This means that ES plays a role in supporting the actions of T cells.

The subcycled Newmark algorithm

The popular Newmark algorithm, used for implicit direct integration of structural dynamics, is extended by means of a nodal partition to permit use of different timesteps in different regions of a structural model. The algorithm developed has as a special case an explicit-explicit subcycling algorithm previously reported by Belytschko, Yen and Mullen. That algorithm has been shown, in the absence of damping or other energy dissipation, to exhibit instability over narrow timestep ranges that become narrower as the number of degrees of freedom increases, making them unlikely to be encountered in practice. The present algorithm avoids such instabilities in the case of a one to two timestep ratio (two subcycles), achieving unconditional stability in an exponential sense for a linear problem. However, with three or more subcycles, the trapezoidal rule exhibits stability that becomes conditional, falling towards that of the central difference method as the number of subcycles increases. Instabilities over narrow timestep ranges, that become narrower as the model size increases, also appear with three or more subcycles. However by moving the partition between timesteps one row of elements into the region suitable for integration with the larger timestep these the unstable timestep ranges become extremely narrow, even in simple systems with a few degrees of freedom. As well, accuracy is improved. Use of a version of the Newmark algorithm that dissipates high frequencies minimises or eliminates these narrow bands of instability. Viscous damping is also shown to remove these instabilities, at the expense of having more effect on the low frequency response.

Xerostomia in Sjogren`s syndrome and lupus erythematosus: a comparative histological and immunofluorescence study of minor salivary glands alterations

Background: Xerostomia is a symptom that can be triggered by chronic diseases such as Sjogren`s syndrome (SS) and lupus erythematosus (LE). Many authors regard most cases of salivary hypofunction in LE to secondary SS. Others believe that salivary changes in patients with LE might reflect a multisystem presentation of the disease. The present study compared histopathological and direct immunofluorescence (DIF) alterations in salivary glands of patients with xerostomia and diagnosis of LE or SS. Methods: Twenty-eight salivary gland biopsies from patients with xerostomia and diagnosed with LE or SS were submitted to histopathological and DIF exams. Results: From the 28 patients, 16 had SS and 12 had LE. In SS, a moderate to intense sialadenitis was detected, with infiltration and destruction of excretory salivary ducts. In LE, mild/moderate sialadenitis with thickening and hyalinization of the ductal basement membrane was observed. DIF revealed that 50% of SS patients presented intercellular ductal IgA deposits, whereas 58% of LE patients showed deposits of IgG in the ductal basement membrane. Conclusions: Alterations in salivary glands of LE patients may be a specific manifestation of the disease (lupus sialadenitis), reflecting its multisystemic presentation, instead of an association of secondary SS and LE.

Influence of ankle functional instability on the ankle electromyography during landing after volleyball blocking

The purpose of this study was to describe, interpret and compare the EMG activation patterns of ankle muscles - tibialis anterior (TA), peroneus longus (PL) and gastrocnemius lateralis (GL) - in volleyball players with and without ankle functional instability (FI) during landing after the blocking movement. Twenty-one players with FI (IG) and 19 controls (CG) were studied. The cycle of movement analyzed was the time period between 200 ms before and 200 ms after the time of impact determined by ground reaction forces. The variables were analyzed for two different phases: pre-landing (200 ms before impact) and post-landing (200 ms after impact). The RMS values and the timing of onset activity were calculated for the three studied muscles, in both periods and for both groups. The co-activation index for TA and PL, TA and GL were also calculated. Individuals with FI presented a lower RMS value pre-landing for PL (CG = 43.0 perpendicular to 22.0; IG = 26.2 perpendicular to 8.4, p < 0.05) and higher RMS value post-landing (CG = 47.5 perpendicular to 13.3; IG = 55.8 perpendicular to 21.6, p < 0.10). Besides that, in control group PL and GL activated first and simultaneously, and TA presented a later activation, while in subjects with FI all the three muscles activated simultaneously. There were no significant differences between groups for co-activation index. Thus, the rate of contraction between agonist and antagonist muscles is similar for subjects with and without FI but the activation individually was different. Volleyball players with functional instability of the ankle showed altered patterns of the muscles that play an important role in the stabilization of the foot-ankle complex during the performance of the blocking movement, to the detriment of the ligament complex, and this fact could explain the usual complaints in these subjects. (C) 2007 Elsevier Ltd. All rights reserved.

Photodegradation of irinotecan (CPT-11) in aqueous solutions: Identification of fluorescent products and influence of solution composition

The photodegradation of irinotecan (CPT-11), the semisynthetic derivative of the antitumor alkaloid 20(S)-camptothecin, has been investigated. The drug was exposed to laboratory light for up to 5 days in 0.9% saline solution (pH 8.5). Five significant photodegradation products were observed and a high-performance liquid chromatography (HPLC) assay was employed to isolate them from CPT-11 using gradient conditions. The structures were elucidated by nuclear magnetic resonance spectroscopy and tandem mass spectrometry and shown to be the result of extensive modifications of the lactone ring of CPT-11. Three of the compounds were found to belong to the mappicine group of alkaloids. In addition, the effect of light on the stability of CPT-11 in aqueous solutions and biological fluids was also assessed, Potassium phosphate buffers (0.05 M, pH 5.0-8.2) and saline, plasma, urine, and bile solutions containing 20 mu M CPT-11 were equilibrated in the dark for 24 h before being exposed to laboratory light for up to 171 h at ambient temperature. Four of the five identified photodegradation products were observed and quantitated by isocratic HPLC, using a different detection mode (fluorescence) than the one used for gradient elution, In general, CPT-11 was found to be unstable under neutral and alkaline conditions for all solutions investigated, with the exception of bile. We conclude that CPT-11 is photolabile and that care should be taken to protect samples, particularly those intended for the isolation and identification of novel metabolites of CPT-11.

Vascular endothelial growth factor and beta-human chorionic gonadotropin are associated with trophoblastic invasion into the tubal wall in ectopic pregnancy

Objective: To assess the association between the depth of trophoblastic penetration into the tubal wall with serum concentrations of vascular endothelial growth factor (VEGF) and beta-hCG and to assess its predictive value. Design: Prospective study. Setting: Tertiary care university hospital. Patient(s): Thirty patients with ampullary pregnancy undergoing salpingectomy were analyzed. Intervention(s): Trophoblastic invasion was histologically classified as stage I when limited to the tubal mucosa, stage II when extending to the muscle layer, and stage III in the case of complete tubal wall infiltration. Main Outcome Measure(s): The relation between depth of trophoblastic infiltration into the tubal wall with VEGF and beta-hCG serum concentrations on the day of surgery. Result(s): An association between the depth of trophoblastic invasion and maternal serum concentrations of VEGF and beta-hCG was observed. VEGF levels of 297.2 pg/mL showed 100.0% sensitivity and 90.0% specificity for stage I, and levels of 440.1 pg/mL showed 81.8% sensitivity and 88.8% specificity for stage III. Beta-hCG levels of 2590.0 mIU/mL showed 88.9% sensitivity and 80.0% specificity for stage I, and levels of 10,827.0 mUI/mL showed 72.7% sensitivity and 88.9% specificity for stage III. Conclusion(s): Maternal serum VEGF and beta-hCG concentrations are associated with depth of trophoblastic penetration into the tubal wall. (Fertil Steril (R) 2010;94:1595-600. (C) 2010 by American Society for Reproductive Medicine.)

Transvaginal ultrasonography with bowel preparation is able to predict the number of lesions and rectosigmoid layers affected in cases of deep endometriosis, defining surgical strategy

Successful surgical treatment of deep bowel endometriosis depends on obtaining detailed information about the lesions, prior to the procedure. The objective of this study was to determine the capability of transvaginal ultrasonography with bowel preparation (TVUS-BP) to predict the presence of one or more rectosigmoid nodules and the deepest bowel layer affected by the disease. A prospective study of 194 patients with clinical and TVUS-BP suspected deep endometriosis submitted to videolaparoscopy. Image data were compared with surgical and histological results. With respect to bowel nodule detection and presence of at least two rectosigmoid lesions, TVUS-BP had a sensitivity of 97 and 81%, specificity 100 and 99%, positive predictive value (PPV) 100 and 93% and negative predictive value (NPV) 98 and 96%, respectively. Regarding diagnosis of infiltration of the submucosal/mucosal layer, TVUS-BP had a sensitivity of 83%, specificity 94%, PPV 77%, NPV 96%. These findings show that TVUS-BP is an adequate exam for evaluating the presence of one or more rectosigmoid nodules and the deepest layer affected in deep infiltrating bowel endometriosis, confirming the importance of this technique for defining the most appropriate surgical strategy to be implemented.

Alterations in Cytokine Profile and Dendritic Cells Subsets in Peripheral Blood of Rheumatoid Arthritis Patients before and after Biologic Therapy

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic joint inflammation and continuous immune cell infiltration in the synovium. These changes are linked to inflammatory cytokine release, leading to eventual destruction of cartilage and bone. During the last decade new therapeutic modalities have improved the prognosis, with the introduction of novel biological response modifiers including anti-TNF alpha CTLA4Ig and, more recently, anti-IL6. In the present study we looked at the immunological effects of these three forms of therapy. Serum, obtained from patients with RA was analyzed for TNF alpha, IL6, IL10, IFN gamma, and VEGF, and in parallel, circulating plasmacytoid and myeloid dendritic cells (DC) were enumerated before and after three infusions of the respective biological treatments. After treatment with anti-IL6, we found a significant reduction of IL6 and TNF alpha levels and the percentage of both DC subsets decreased. Although the results did not reach statistical significance for anti-TNF alpha treatment, similar trends were observed. Meanwhile, CTLA4Ig therapy led to the reduction IFN gamma levels only. None of the treatments modified significantly VEGF or IL10 levels. These findings may explain why patients with RA improve more rapidly on IL-6 therapy than with the other two modalities.

Early short-term versus prolonged low-dose methylprednisolone therapy in acute lung injury

The present study compared the effects of early short-term with prolonged low-dose corticosteroid therapy in acute lung injury (ALI). In total, 120 BALB/c mice were randomly divided into five groups. In the control group, saline was intratracheally (i.t.) instilled. In the ALI group, mice received Escherichia coli lipopolysaccharide (10 mu g i.t.). ALI animals were further randomised into four subgroups to receive saline (0.1 mL i.v.) or methylprednisolone (2 mg center dot kg(-1) i.v.) at 6 h, 24 h or daily (for 7 days, beginning at day 1). At 1, 3 and 8 weeks, in vivo and in vitro lung mechanics and histology (light and electron microscopy), collagen and elastic fibre content, cytokines in bronchoalveolar lavage fluid and the expression of matrix metalloproteinase (MMP)-9 and -2 were measured. In vivo (static elastance and viscoelastic pressure) and in vitro (tissue elastance and resistance) lung mechanics, alveolar collapse, cell infiltration, collagen and elastic fibre content and the expression of MMP-9 and MMP-2 were increased in ALI at 1 week. Methylprednisolone led to a complete resolution of lung mechanics, avoided fibroelastogenesis and the increase in the expression of MMP-9 and MMP-2 independent of steroid treatment design. Thus, early short-term, low-dose methylprednisolone is as effective as prolonged therapy in acute lung injury.