Correction to: Influence of oral anticoagulation on success rates and risk of bleeding events after iStent inject implantation combined with phacoemulsification

Graefe's Archive for Clinical and Experimental Ophthalmology - The published online version contains mistake as the author's first name and last name have been interchanged as "Hild...     

Ligand-dependent activation of ER{beta} lowers blood pressure and attenuates cardiac hypertrophy in ovariectomized spontaneously hypertensive rats

AIMS: The biological effects of oestrogens are mediated by two different oestrogen receptor (ER) subtypes, ERalpha and ERbeta, which might play different, redundant, or opposing roles in cardiovascular disease. Previously, we have shown that the selective ERalpha agonist 16alpha-LE2 improves vascular relaxation, attenuates cardiac hypertrophy, and increases cardiac output without lowering elevated blood pressure in spontaneously hypertensive rats (SHR). Because ERbeta-deficient mice exhibit elevated blood pressure and since the ERbeta agonist 8beta-VE2 attenuated hypertension in aldosterone-salt-treated rats, we have now tested the hypothesis that the isotype-selective ERbeta agonist 8beta-VE2 might be capable of lowering elevated blood pressure in ovariectomized SHR. METHODS AND RESULTS: Treatment of ovariectomized SHR with 8beta-VE2 for 12 weeks conferred no uterotrophic effects but lowered elevated systolic blood pressure (-38 +/- 5 mmHg, n = 31, P < 0.001 vs. placebo) as well as peripheral vascular resistance (-31.3 +/- 4.6%, P < 0.001 vs. placebo). 8beta-VE2 enhanced aortic ERbeta expression (+75.7 +/- 7.1%, P < 0.01 vs. placebo), improved NO-dependent vasorelaxation, augmented phosphorylation of the vasodilator-stimulated phosphoprotein in isolated aortic rings (P < 0.05 vs. placebo), increased cardiac output (+20.4 +/- 2.5%, P < 0.01 vs. placebo), and attenuated cardiac hypertrophy (-22.2 +/- 3.2%, p < 0.01 vs. placebo). 8beta-VE2, in contrast to oestradiol, did not enhance cardiac alpha-myosin heavy chain expression. CONCLUSION: Ligand-dependent activation of ERbeta confers blood pressure lowering effects in SHR that are superior to those of 17beta-estradiol or the ERalpha agonist 16alpha-LE2 and attenuates cardiac hypertrophy primarily by a reduction of cardiac afterload without promoting uterine growth.     

ATLS adherence in the transfer of rural trauma patients to a level I facility

Background

Injury sustained in rural areas has been shown to carry higher mortality rates than trauma in urban settings. This disparity is partially attributed to increased distance from definitive care and underscores the importance of proper primary trauma management prior to transfer to a trauma facility. The purpose of this study was to assess Advanced Trauma Life Support (ATLS) guideline adherence in the management of adult trauma patients transferred from rural hospitals to a level I facility.

Methods

We performed a retrospective analysis of all adult major trauma patients transferred ≥50 km from an outlying hospital to a level I trauma centre from 2007 through 2009. Transfer practices were evaluated using ATLS guidelines.

Results

646 patients were analyzed. Mean age was 40.5 years and 94% sustained blunt injuries with a median Injury Severity Score (ISS) of 22. Median transport distance was 253 km. Among all patients, there were notable deficiencies (<80% adherence) in 8 of 11 ATLS recommended interventions, including patient rewarming (8% adherence), chest tube insertion (53%), adequate IV access (53%), and motor/sensory exam (72%). Patients with higher ISS scores, and those transferred by air were more likely to receive ATLS recommended interventions.

Conclusions

Key aspects of ATLS resuscitation guidelines are frequently missed during transfer of trauma patients from the periphery to level I trauma centres. Comprehensive quality improvement initiatives, including targeted education, telemedicine and trauma team training programmes could improve quality of care.     

F-FLT-PET for detection of rectal cancer

Purpose: This pilot study was undertaken to examine the ability of ¹⁸F-3′-fluoro-3′-deoxy-l-thymidine positron emission tomography (¹⁸F-FLT-PET)to detect rectal cancer, to identify pathologic lymph nodes and to determine the accuracy of tumour length estimation in comparison with computer tomography (CT). Methods: Nine patients with biopsy proven rectal cancer underwent CT and ¹⁸F-FLT-PET scanning prior to short-term pre-operative radiotherapy (5 × 5 Gy). Within 10 days after the start of radiotherapy a surgical resection was performed. Tumour lengths and regional lymph node visualisation on both imaging modalities were compared with pathology findings. Results: All tumours were visible on CT. ¹⁸F-FLT-PET visualised 7 out of 9 tumours (78%). The pathology-based tumours lengths correlated better with CT as compared to FLT-PET(r = 0.91, p < 0.01). ¹⁸F-FLT-PET was not able to visualise pathologic lymph nodes. However, CT identified all patients with pathologic lymph nodes. Conclusion: Primary rectal cancer can be visualised by ¹⁸F-FLT-PET in the majority of cases but not in all. However, ¹⁸F-FLT-PET was not able to identify pathologic lymph nodes. Therefore, we conclude that ¹⁸F-FLT-PET has limited value for the detection of pathologic lymph nodes and tumour delineation in rectal cancer.     

Intensified Adjuvant IFADIC Chemotherapy for Adult Soft Tissue Sarcoma: A Prospective Randomized Feasibility Trial

Purpose. The present prospective randomized adjuvant trial was carried out to compare the toxicity, feasibility and efficacy of augmented chemotherapy added to hyperfractionated accelerated radiotherapy after wide or marginal resection of grade 2 and grade 3 soft tissue sarcoma (STS).Patients and methods. Fifty-nine patients underwent primary surgery by wide or marginal excision and were subsequently randomized to receive radiotherapy alone or under the addition of six courses of ifosfamide (1500 mg/m(2) , days 1-4), dacarbazine (DTIC) (200 mg/m(2) , days 1-4) and doxorubicin (25 mg/m(2) , days 1-2) administered in 14-day-intervals supported by granulocyte-colony stimulating factor (30 x 10(6) IU/day, s.c.) on days 5-13. According to the randomization protocol, 28 patients received radiotherapy only, whereas 31 patients were treated with additional chemotherapy.Results. The relative ifosfamide-doxorubicin-DTIC (IFADIC) dose intensity achieved was 93%. After a mean observation period of 41+/-19.7 months (range, 8.1-84 months), 16 patients (57%) in the control group versus 24 patients (77%) in the chemotherapy group were free of disease (p>0.05).Within the control group, tumor relapses occurred in 12 patients (43%;six patients with distant metastases, two with local relapse, four with both) versus seven patients (23%; five patients with distant metastases, one with local recurrence, one with both) from the chemotherapy group. Relapse-free survival (RFS) (p=0.1), time to local failure (TLF) (p=0.09), time to distant failure (TDF) (p=0.17) as well as overall survival (OS) (p=0.4) did not differ significantly between the two treatment groups. Treatment-related toxicity was generally mild in both treatment arms.Conclusion. We conclude that the safety profile of intensified IFADIC added to radiotherapy was manageable and tolerable in the current setting. Inclusion of intensified IFADIC was not translated into a significant benefit concerning OS, RFS, TLF andTDF as compared with radiotherapy only, although a potential benefit of chemotherapy for grade 3 STS patients needs to be validated in prospective randomized trials including larger patient numbers.     

Reduced basal nitric oxide bioavailability and platelet activation in young spontaneously hypertensive rats

OBJECTIVE: To investigate the role of basal nitric oxide (NO) bioavailability for platelet activation in young spontaneously hypertensive rats before onset of hypertension. Phosphorylation of the vasodilator-stimulated phosphoprotein (VASP) in platelets was used as a sensitive monitor of in vivo NO bioavailability. METHODS AND RESULTS: Whole blood samples were taken from 10-week-old Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). In vivo surface-expression of P-selectin and platelet-binding of fibrinogen were assessed by flow cytometry. Platelet VASP-phosphorylation at its serine 239 (Ser239) and serine 157 (Ser157) residues was assessed using specific antibodies to determine NO bioavailability in vivo, and compared with endothelial vasomotor function. The increment in vascular tone following inhibition of NO-synthase in slightly preconstricted aortic rings was reduced indicating less NO formation under physiological stimulation (WKY 71.1+/-4.1%; SHR 57.8+/-2.4%, P<0.05). In vivo platelet VASP-phosphorylation was significantly reduced at both phosphorylation sites in SHR (mean fluorescence for Ser239: WKY: 15.2+/-0.6; SHR: 11.7+/-0.5, P<0.01; Ser157: WKY: 53.0+/-3.0; SHR: 35.0+/-3.5, P<0.05). Surface-expression of P-selectin and membrane-bound fibrinogen were significantly enhanced in SHR compared with WKY (P-selectin: WKY: 23.2+/-3.4; SHR 58.3+/-7.9, P<0.001; platelet-bound fibrinogen: WKY: 8.6+/-0.5; SHR: 13.5+/-1.1, P<0.001). In vitro preincubation of platelets with the NO donor sodium nitroprusside normalized platelet surface-expression of P-selectin in SHR. CONCLUSION: Using VASP-phosphorylation as a sensitive monitor of in vivo NO bioavailability, these data provide evidence that reduced vascular NO formation in vivo contributes to increased platelet activation in young SHR.     

Increased platelet activation in young Zucker rats with impaired glucose tolerance is improved by acarbose

Patients with diabetes display increased platelet activation. Recent data show a markedly increased risk for cardiovascular events already in pre-diabetic individuals with impaired glucose tolerance (IGT). We investigated whether IGT is associated with platelet activation. Blood samples were collected from young lean (control) and obese Zucker rats, an established model of IGT, after single oral application of sucrose (4 g.kg-1). Platelet-bound fibrinogen and platelet surface-expression of P-selectin were assessed as indices of platelet activation using flow cytometry. In lean Zucker rats, acute sucrose application induced fibrinogen-binding and P-selectin surface-expression, which was prevented by co-administration of acarbose (10 mg.kg-1). In obese Zucker rats, platelet activation was already maximally increased under baseline conditions with no significant increase after sucrose application. Chronic treatment with acarbose (15 mg.kg-1.day-1) significantly reduced platelet activation in these animals. Acute ingestion of sucrose induces platelet activation which is prevented by acarbose. IGT is associated with marked platelet activation that can be reduced by chronic administration of acarbose. The positive modulation of platelet activation by acarbose may contribute to the reduction of cardiovascular events in patients with IGT.