Do preoperative cytokine levels offer a prognostic factor for polypropylene mesh erosion after suburethral sling surgery for stress urinary incontinence?

When polypropylene meshes are used in reconstructive urogynecological surgery, the erosion rates vary from 3.3% to 14% and causative factors for such erosions are still unknown in many cases. Therefore, the aim of our study was to establish the role of immunologic factors in the process of polypropylene tapes erosions after suburethral sling procedures. Serum concentrations of tumor necrosis factor α, interleukin (IL)-2, IL-4, IL-5, IL-10, and interferon (IFN)-γ were estimated in 123 patients suffering from stress urinary incontinence preoperatively and during 12 months follow-up using Human Th1/Th2 Cytokine Cytometric Bead Array I kit. The same immunological assessment was performed in each case of detected tape erosion. Statistical calculation was performed using UNIVARIATE, CORR, and NPAR1WAY procedures from Statistical Analysis System. The unpaired Student’s t test, nonparametric Mann–Whitney U test, and Wilcoxon tests were used. Preoperative IFN-γ concentration was significantly higher in women with subsequent polypropylene mesh erosion when compared to women with successful outcome (p < 0.05). Th1 cytokine profile may be related to the risk of the vaginal erosions following placement of polypropylene meshes. The way to lower erosion rate may involve exclusion of the patients immunologically prone to synthetic material erosion. The factor which can help to select such patients could be preoperative level of IFN-γ.     

Usefulness of perfusion weighted magnetic resonance imaging with signal-intensity curves analysis in the differential diagnosis of sellar and parasellar tumors: Preliminary report

Purpose

The most common pituitary tumors are adenomas, which however may be mimicked by other tumors that can show a very similar appearance in plain MRI. The aim of our study was to evaluate the usefulness of perfusion weighted MR imaging (PWI), including signal-intensity curves analysis in the differential diagnosis of sellar/parasellar tumors.

Methods

Forty-one patients with sellar/parasellar tumors (23 macroadenomas, 10 meningiomas, 5 craniopharyngiomas, 1 intrasellar hemangioblastoma, 1 intrasellar prostate cancer metastasis, 1 suprasellar glioma), underwent plain MRI followed by PWI using a 1.5T unit. In each tumor, the mean and maximum values of relative cerebral blood volume (rCBV), as well as the relative peak height (rPH) and the relative percentage of signal intensity recovery (rPSR) were calculated.

Results

The high perfusion tumors were: macroadenomas, meningiomas, squamous-papillary type of craniopharyngiomas, hemangioblastoma, glioma and metastasis. The low perfusion neoplasms included adamantinomatous type of craniopharyngiomas. By comparing adenomas and meningiomas, we found statistically significant differences in the mean and maximum rCBV values (p = 0.026 and p = 0.019, respectively), but not in rPH and rPSR. The maximum rCBV values >7.14 and the mean rCBV values >5.74 with the typical perfusion curve were very suggestive of the diagnosis of meningioma. There were differences between adenomas and other high perfusion tumors in rPH and rPSR values.

Conclusions

PWI can provide additional information helpful in differential diagnosis of sellar/parasellar tumors. In our opinion PWI, as an easy to perform and fast technique should be incorporated into the MR protocol of all intracranial neoplasms including sellar/parasellar tumors.     

Bromodeoxyuridine Labeling Index as an Indicator of Early Tumor Response to Preoperative Radiotherapy in Patients with Rectal Cancer

Purpose Assessment of tumor proliferation rate using Bromodeoxyuridine labeling index (BrdUrdLI) as a possible predictor of rectal cancer response to preoperative radiotherapy (RT). Methods and material Ninety-two patients were qualified either to short RT (5 Gy/fraction/5 days) and surgery about 1 week after RT (schedule I), or to short RT and 4–5 weeks interval before surgery (schedule II). Tumor samples were taken twice from each patient: before RT and at the time of surgery. The samples were incubated with BrdUrd for 1 h at 37°C, and the BrdUrdLI was calculated as a percentage of BrdUrd-labeled cells. Results Thirty-eight patients were treated according to schedule I and 54 patients according to schedule II. Mean BrdUrdLI before RT was 8.5% and its value did not differ between the patients in the two compared groups. After RT tumors showed statistically significant growth inhibition (reduction of BrdUrdLI). As the pretreatment BrdUrd LI was not predictive for early clinical and pathologic tumor response, prognostic role of the ratio of BrdUrdLI after to BrdUrdLI before RT was considered. The ratios were calculated separately for fast (BrdUrd LI > 8.5%) and slowly (BrdUrd LI ≤ 8.5%) proliferating tumors and correlated with overall treatment time (OTT, i.e., time from the first day of RT to surgery). One month after RT, accelerated proliferation was observed only in slowly proliferating tumors. Conclusions Pretreatment BrdUrdLI was not predictive for early clinical and pathologic tumor response. The ratio after/before RT BrdUrdLI was correlated to inhibition of proliferation in responsive tumors. The paper was presented at ECCO 13, October 30 to November 03, 2005 in Paris, France     

EphB4 enhances the process of endochondral ossification and inhibits remodeling during bone fracture repair

Previous reports have identified a role for the tyrosine kinase receptor EphB4 and its ligand, ephrinB2, as potential mediators of both bone formation by osteoblasts and bone resorption by osteoclasts. In the present study, we examined the role of EphB4 during bone repair after traumatic injury. We performed femoral fractures with internal fixation in transgenic mice that overexpress EphB4 under the collagen type 1 promoter (Col1‐EphB4) and investigated the bone repair process up to 12 weeks postfracture. The data indicated that Col1‐EphB4 mice exhibited stiffer and stronger bones after fracture compared with wild‐type mice. The fractured bones of Col1‐EphB4 transgenic mice displayed significantly greater tissue and bone volume 2 weeks postfracture compared with that of wild‐type mice. These findings correlated with increased chondrogenesis and mineral formation within the callus site at 2 weeks postfracture, as demonstrated by increased safranin O and von Kossa staining, respectively. Interestingly, Col1‐EphB4 mice were found to possess significantly greater numbers of clonogenic mesenchymal stromal progenitor cells (CFU‐F), with an increased capacity to form mineralized nodules in vitro under osteogenic conditions, when compared with those of the wild‐type control mice. Furthermore, Col1‐EphB4 mice had significantly lower numbers of TRAP‐positive multinucleated osteoclasts within the callus site. Taken together, these observations suggest that EphB4 promotes endochondral ossification while inhibiting osteoclast development during callus formation and may represent a novel drug target for the repair of fractured bones. © 2013 American Society for Bone and Mineral Research.     

Transpupillary thermotherapy in exudative age-related macular degeneration

PURPOSE: Assessment of TTT results in patients with exudative age-related macular degeneration. MATERIAL AND METHODS: The study comprised of 65 patients (73 eyes), in age 50-84 years (average age-75 yrs). The diagnosis of exudative AMD was established on the basis of fundus examination and fluorescein angiography (FA) and in some cases on indocyanine green angiography. The baseline visual acuity (VA) ranged from counting fingers at 50 cm to 0.8. In 31 (42.5%) eyes occult CNV, in 11 (15%) minimally classic CNV and in 31 (42.5%) eyes predominantly classic CNV were observed. Subfoveal CNV was present in 70 (95.9%) eyes and perifoveal in 3 (4.1%). TTT was delivered using a diode laser at 810 nm wavelength, a spot size of 1.2 to 4.5 mm and a duration of 60 seconds for each spot with power settings between 320-800 mW. Follow-up examinations were carried out every 10-12 weeks. In cases with persistent leakage from CNV in late frames of FA a retreatment was performed. The follow-up period ranged from 6 to 28 months (average - 9.8 months). RESULTS: Visual acuity improved in 22 (30.1%) eyes, stabilized in 34 (46.6%) and deteriorated in 17 (23.3%). Fluorescein angiography showed no CNV leakage in 58 (79.5%) eyes. In 56 (71.8%) with regression of leakage in fluorescein angiography improvement or stabilization of visual acuity was detected. Subretinal haemorrhages after TTT were observed in 4 eyes (5.5%). At the end of the follow-up period fibrosis of CNV was detected in 12 eyes (16.4%). CONCLUSIONS: TTT is effective and safe method of treatment of occult and classic CNV in a course of wet AMD. In a majority of cases TTT results in total or partial regression of CNV and stabilization of visual acuity.     

Inhibition of NF-κB-dependent cytokine and inducible nitric oxide synthesis by the macrocyclic ellagitannin oenothein B in TLR-stimulated RAW 264.7 macrophages

Immunomodulatory effects of oenothein B (1), a macrocyclic ellagitannin from various Onagraceae species, have been described previously. However, the mechanisms underlying the anti-inflammatory activity of 1 have not been fully clarified. The effects of 1 were investigated on inducible nitric oxide synthase, TLR-dependent and TLR-independent signal transduction cascades, and cytokine expression using murine macrophages (RAW 264.7). Compound 1 (10-60 μg/mL) reduced NO production, iNOS mRNA, and iNOS protein levels in a dose-dependent manner, without inhibition of iNOS enzymatic activity. It reduced the binding of the NF-κB p50 subunit to the biotinylated-consensus sequence and decreased nuclear p65 translocation. Gallic acid as a subunit of the macrocyclic ellagitannin 1 showed a far lower inhibitory activity. Nitric oxide production was reduced by 1 after stimulation using TLR2 (Pam2CSK4) and TLR4 (Kdo2) agonists, but this compound did not inhibit inducible nitric oxide synthesis after stimulation using interferon-gamma. IL-1beta, IL-6, and TNF-alpha mRNA synthesis was clearly reduced by the addition of 1. Oenothein B (1) inhibits iNOS after stimulation with LPS, TLR2, and TLR4 agonists via inhibition of TLR/NF-κB-dependent inducible nitric oxide and cytokine synthesis independent from IFN-gamma/JAK/STAT pathways. The full molecular structure of this macrocyclic ellagitannin seems to be required for its immunomodulatory actions.     

Pharmacological versus invasive treatment in patients with atrial fibrillation

Aim of this prospective study was to assess quality of life (QoL), left ventricular (LV) function and exercise performance in two groups of patients (pts) with atrial fibrillation (Af) treated with: radiofrequency catheter ablation (RFA) and antiarrhythmic drugs (AA). Between 1996 and 2000 - 74 patients, 28 women, with drug refractory Af were enrolled by clinical indications for two modes of therapy: RFA and AA. RFA group consisted of 38 pts, 63.7 +/- 11.5 years old: 28 pts with RF AV Node ablation and pacemaker implantation (PI) and 10 pts with AV Node modification or right atrial isthmus RF ablation due to Af conversion to atrial flutter (Aflu) during medical therapy. AA group consisted of 36 pts, aged 59.7 +/- 13.8 years. Patients from RFA group suffered significantly more serious diseases than pts from AA group. No significant (sign.) differences between two groups were found in age, gender, arrhythmia history and number of AA taken. Pts were analyzed before entry, after 3 and 12 months of follow-up (3 mo. FU, 12 mo. FU) with following indices: LV function (Echo: EF & FS), exercise performance (treadmill test), QoL questionnaires, number of hospital admissions connected to arrhythmia or procedures (RFA & PI), number of AA drugs taken in RFA group. RFA group: Two deaths occurred due to end stage respiratory insufficiency (COPD), one pt required reposition of pacemaker lead. AA group: 3 pts required RFA due to uncontrolled Af/Aflu (AV Node ablation with PI - 1 pt, right atrial isthmus ablation - 2 pts). Analysis of two patients groups: LV function: Sign. improvement (EF & FS) in both groups in 12 mo. FU; Exercise performance: no sign. changes in 3 and 12 mo. FU. QoL: Arrhythmia scale: 3 mo. FU sign. reduction in both groups; 12 mo. FU reduction in RFA group only; Anxiety scale: 3 and 12 mo. FU sign. reduction of anxiety level in RFA group; Exercise and activity scales: 3 and 12 mo. FU sign. improvement in RFA group. During 3 and 12 mo. FU sign. less pts from RFA group required hospital admission versus pts from AA group. Sign. reduction in AA was noted in RFA group. Patients with symptomatic Af treated with RFA benefit from this kind of therapy more than patients treated with AA. Quality of life improvement visible in short term observation in patients from RFA group is still present after one year observation. Improvement in LV function is observed after one year in both groups of pts with Af.     

Towards potent but less toxic nanopharmaceuticals – lipoic acid bioconjugates of ultrasmall gold nanoparticles with an anticancer drug and addressing unit

Modification of ultrasmall gold nanoparticles (AuNPs) with the lipoic acid derivative of folic acid was found to enhance their accumulation in the cancer cell, as compared to AuNPs without addressing units. The application of lipoic acid enabled the control of the gold nanoparticle functionalities leading to enhanced solubility and allowing for attachment of both the folic acid and the cytotoxic drug, doxorubicin. More robust attachment of doxorubicin to the nanoparticle through the amide bond resulted in toxicity comparable with that of the drug alone, opening a new perspective for designing more potent, but less toxic nanopharmaceuticals. The increased uptake was accompanied by pronounced nuclear accumulation and observable cytotoxicity. Doxorubicin binding via covalent amide bonds enhanced stability of the whole drug vehicle and provided much better control over doxorubicin release in the cell environment, as compared to physical adsorption or pH sensitive bonding commonly used for anthracycline carriers. Confocal microscopy revealed that the bond was stable in the cytoplasm for 22 h. The ability to slow down the rate of drug release may be crucial for the application in sustained anticancer drug delivery. Biological analyses performed using MTT assay and confocal microscopy confirmed that the ultrasmall AuNPs with the lipoic acid derivative of folic acid exhibit relatively low cytotoxicity, however when loaded with a chemotherapeutic, they cause a significant reduction in the cell viability.

Modification of ultrasmall gold nanoparticles (AuNPs) with the lipoic acid derivative of folic acid was found to enhance their accumulation in the cancer cell, as compared to AuNPs without addressing units.     

Late recovery of awareness in prolonged disorders of consciousness –a cross-sectional cohort study

Purpose: To detect any improvement of awareness in prolonged disorders of consciousness in the long term.

Methods: A total of 34 patients with prolonged disorders of consciousness (27 vegetative state and seven minimally conscious state; 16 males; aged 21–73) were included in the study. All patients were initially diagnosed with vegetative/minimally conscious state on admission to our specialist neurological rehabilitation unit. Re-assessment was performed 2–16?years later using Coma Recovery Scale-Revised.

Results: Although remaining severely disabled, 32% of the patients showed late improvement of awareness evidenced with development of non-reflexive responses such as reproducible command following and localization behaviors. Most of the late recoveries occurred in patients with subarachnoid hemorrhage (5/11, 45.5%). The ages of patients within the late recovery group (Mean?=?45, SD?=?11.4) and non-recovery group (Mean?=?43, SD?=?15.5) were not statistically different (p?=?0.76).

Conclusions: This study shows that late improvements in awareness are not exceptional in non-traumatic prolonged disorders of consciousness cases. It highlights the importance of long-term follow up of patients with prolonged disorders of consciousness, regardless of the etiology, age, and time passed since the brain injury. Long-term follow up will help clinicians to identify patients who may benefit from further assessment and rehabilitation. Although only one patient achieved recovery of function, recovery of awareness may have important ethical implications especially where withdrawal of artificial nutrition and hydration is considered.

• Implications for rehabilitation

• Long-term regular follow-up of people with prolonged disorders of consciousness is important.

• Albeit with poor functional outcomes late recovery of awareness is possible in both traumatic and non-traumatic prolonged disorders of consciousness cases.

• Recovery of awareness has significant clinical and ethical implications especially where withdrawal of artificial nutrition and hydration is considered.