The role of histone demethylases in cancer therapy

Reversible histone methylation has emerged in the last few years as an important mechanism of epigenetic regulation. Histone methyltransferases and demethylases have been identified as contributing factors in the development of several diseases, especially cancer. Therefore, they have been postulated to be new drug targets with high therapeutic potential. Here, we review histone demethylases with a special focus on their potential role in oncology drug discovery. We present an overview over the different classes of enzymes, their biochemistry, selected data on their role in physiology and already available inhibitors.     

Promoting positive well‐being in employed mothers: A pilot study

In this quasi‐experimental pilot study, women who were returning to work within 6 months after the birth of a first baby were assigned to participate in a control group (n = 13) or a six‐session small group intervention (n = 18). The content of the group intervention was developed based on a stress and coping framework (Lazarus & Folkman, 1984).”; The experimental and control groups were surveyed at 2 months after their return to employment and on their baby's first birthday on measures of well‐being in marriage, work, and parenting. Repeated measures analysis of covariance was used to examine differences over time between the experimental and control group with length of maternity leave and number of hours worked as covariates. Participants in the intervention reported increasing levels of marital satisfaction over time, whereas the control group experienced a decline in marital satisfaction over time (p = .04). Implications for practice and research are presented.     

Call for Papers/Directions for A.E.H. Contributors

The effects of industrial noise on resting heart rate and blood pressure were studied in 3 105 blue-collar workers. Heart rate and blood pressure were measured in different workers at various times during the workday. After controlling for several possible confounders, we found that resting heart rate in females was associated positively with noise intensity (p = .036) and with time of day (p = .054). In males, resting heart rate was associated with noise intensity; however, such association was related to time of day (p = .046). No such associations were found for blood pressure in either sex. We plotted the mean resting heart rate by time of day for workers exposed to high [≥ 80 db(A)] and low noise, and no difference was evident with respect to morning heart rate in either sex. After 4 h of noise exposure for males (and less time for females), individuals who were exposed to high noise had higher heart rates; however, in females this was not observed at the end of the workday. Thus, recurrent daily exposure to high noise at work has an acute, though not residual, effect on resting heart rate.     

美学区软组织水平和骨水平植体周围骨丧失和牙龈生物型的分析

目的: 植体周围一定程度的骨丧失可能会给牙种植治疗的美观效果带来不利影响。这种情况可能更容易影响软组织水平（Tissue-Level, TL）设计,因此,当强调形态的美观自然性时,骨组织水平（Bone-Level, BL）设计可能更有优势。除了植体的设计,牙龈生物型也被认为是维持牙槽骨稳定的重要因素。本研究拟针对具有不同牙龈生物型的患者,在其美学区域行软组织水平和骨水平牙种植治疗,探究其骨丧失的程度。材料和方法: 对41位患者行20个TL和22个BL种植治疗,术后即刻、术后随访对这42个位点行口内影像学检查;运用计算机技术行牙槽骨高度测量分析;运用TRAN法鉴定患者的牙龈生物型。结果: TL组平均4.9年的存留期里,厚龈型的12颗植体周围平均骨丧失0.21mm（SD：0.43mm）;薄龈型的8颗植体周围平均骨丧失0.05mm（SD：0.47mm;P=0.31）。BL组平均1.9年的存留期里,厚龈型的14颗植体周围骨丧失为-0.03mm（SD：0.38mm）,薄龈型的8颗植体周围骨丧失为+0.09mm（SD：0.32mm;P=0.84）。结论: 分析得到的数据发现,牙槽骨高度的变化与种植设计或是牙龈生物型并无直接相关性。然而在选择种植设计之前,评价软组织的厚度是有利的,其中BL种植设计更能获得自然的外形。为实现以上评价目的,TRAN法是最快速、简易的方法。     

Inhibition of neointimal formation after stent placement with adenovirus-mediated gene transfer of I kappa B alpha in the hypercholesterolemic rabbit model: initial results

PURPOSE: To evaluate the feasibility and efficacy of the local application of a replication-defective adenovirus construct for the expression of the antiinflammatory protein I kappa B alpha, inhibitor of nuclear factor kappa B (NF-kappa B), to reduce neointimal formation after stent placement. MATERIALS AND METHODS: Nitinol stents were implanted in the iliac arteries of hypercholesterolemic rabbits, followed by balloon dilation (30 seconds at 6 atm). Local adenovirus-mediated transfer of I kappa B alpha (3 mL of 10(9) plaque-forming units per milliliter at 6 atm) was performed and compared with three control groups: stent alone, stent plus local delivery of phosphate-buffered saline (PBS) (3 mL at 6 atm), and stent plus local delivery of control adenovirus coding for green fluorescent protein (GFP) (3 mL of 10(9) plaque-forming units per milliliter at 6 atm). A multichannel balloon was used for local drug delivery and balloon dilation. Animals were sacrificed 1 or 4 weeks after treatment. Effective transfection was demonstrated with immunofluorescence staining. Angiographic patency and luminal diameter were evaluated at quantitative angiography. Luminal and neointimal areas were measured on surface-stained ground sections with methylmethacrylate embedding and the cutting-grinding technique. RESULTS: All vessels with stents were patent at angiography. Neointimal area was negligible in all groups 1 week after stent placement (range, 0.42-0.52 mm(2); P =.44; analysis of variance). Neointimal formation was demonstrated in all groups 4 weeks after implantation but was significantly reduced with I kappa B alpha treatment compared with treatment with stent alone (by 22%, from 2.80 mm(2) +/- 0.20 to 2.28 mm(2) +/- 0.14, P =.05), stent plus PBS (by 43%, from 3.26 mm(2) +/- 0.25 to 2.28 mm(2) +/- 0.14, P =.005), and stent plus GFP (by 53%, from 2.32 mm(2) +/- 0.19 to 1.51 mm(2) +/- 0.08, P <.005). CONCLUSION: Local adenovirus-mediated I kappa B alpha gene transfer has the potential to reduce intimal hyperplasia after stent placement.     

Tumor staging of laryngeal and hypopharyngeal carcinomas with functional spiral CT: comparison with nonfunctional CT, histopathology, and microlaryngoscopy

PURPOSE: The purpose of this work was to compare nonfunctional and functional spiral CT in the tumor (T) staging of laryngeal and hypopharyngeal tumors and to correlate the CT results with microlaryngoscopy and postoperative pathology. METHOD: Twenty-six patients (3 women, 23 men) with clinically suspected laryngeal and hypopharyngeal tumors underwent both nonfunctional CT during quiet breathing and functional spiral CT during either a modified Valsalva (n = 19) or E phonation (n = 7) maneuver. CT slice thickness was 3 mm, table feed was 3 mm, and 40-80 ml of intravenous contrast material was administered at a flow of 1.5 ml/s. T stages as determined by nonfunctional and functional CT were compared and correlated with postoperative pathology or microlaryngoscopy. RESULTS: The T stages determined with functional CT were better correlated with postoperative pathology (rS = 0.88, p = 0.001) and microlaryngoscopy (rS = 0.77, p = 0.008) than T stages determined with nonfunctional CT (rS = 0.80, p = 0.001; and rS = 0.51, p = 0.13, respectively). Twelve of 26 patients (46%) had a lower T stage on functional than on nonfunctional CT. In 14 of 26 patients (54%), the T stage was identical with both modalities. In no patients was the T stage increased by functional CT. CONCLUSION: Functional CT appears to be more accurate than nonfunctional CT in the T staging of laryngeal and hypopharyngeal carcinomas. Functional CT also results in lower T stages than nonfunctional CT in a substantial number of patients.     

Korean hand acupressure for motion sickness in prehospital trauma care: a prospective, randomized, double-blinded trial in a geriatric population

Patients with trauma or medical illnesses transported to the hospital by ambulance have a frequent incidence of motion sickness. Because the administration of drugs in the ambulance is prohibited by law in Austria, the noninvasive Korean hand acupressure point at K-K9 may be an alternative against nausea and vomiting. We enrolled 100 geriatric patients with minor trauma, randomizing them into a K-K9 group and a sham acupressure group. We recorded visual analog scores (VAS) for nausea and for the patient's overall satisfaction with the treatment, hemodynamic variables, and peripheral vasoconstriction. In the K-K9 group, a significant (P < 0.01) increase in nausea was recorded in all cases: from VAS of 0 mm to 25 +/- 6 mm. A similarly significant (P < 0.01) increase was registered in the sham group: from VAS of 0 mm to 83 +/- 8 mm. However, at the time of arrival in the hospital, nausea scores were significantly different between the K-K9 group and the sham group (P < 0.01). Although all patients had been vasoconstricted at the emergency site before treatment, there was a significant difference (P < 0.01) between groups with regard to the number of vasoconstricted patients at the hospital (4 and 46 constricted and dilated, respectively, in the K-K9 group versus 48 and 2 constricted and dilated, respectively, in the sham group). On arrival in the hospital, a significant difference (P < 0.01) in heart rate was noted between the K-K9 group and the sham group (65 +/- 6 bpm versus 98 +/- 8 bpm). The patients' overall satisfaction with the provided care was significantly higher (P < 0.01) in the K-K9 group (19 +/- 9 mm VAS) than in the sham group (48 +/- 12 mm VAS). Neither group experienced a significant change in blood pressure. K-K9 stimulation was an effective and simple treatment for nausea during emergency care and significantly improved patient satisfaction. IMPLICATIONS: Korean hand acupressure at the K-K9 point was effective in reducing nausea and subjective symptoms of motion sickness in emergency trauma transport of patients at high risk of motion sickness.     

Prospective randomized trial comparing flutamide as adjuvant treatment versus observation after radical prostatectomy for locally advanced, lymph node-negative prostate cancer

OBJECTIVE: To assess the efficacy and the tolerability of flutamide as adjuvant treatment after radical prostatectomy for locally advanced, lymph node-negative prostate cancer. METHODS: Men with locally advanced, lymph node-negative prostate cancer were randomized after radical prostatectomy to receive either flutamide 750mg daily or no adjuvant treatment. Recurrence-free and overall survival were the study end points. Recurrence was defined as a PSA value greater than 5ng/ml or two values greater than 2ng/ml more than three months apart with increasing tendency or three values greater than 1ng/ml more than three months apart with increasing tendency or any clinical recurrence. RESULTS: 309 patients (157 in the control arm and 152 in the flutamide arm) were eligible for efficacy analysis. The median follow-up was 6.1 years. Recurrence-free survival was better in the flutamide group ( P=0.0041), there was, however, no detectable difference in overall survival ( p=0.92 ). Moreover, there was a considerable toxicity reported in the flutamide group. CONCLUSION: Although having some effect on disease recurrence, adjuvant flutamide treatment does not improve median-term overall survival after radical prostatectomy for locally advanced, lymph node-negative prostate cancer.