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1.
Clin Res Cardiol ; 108(10): 1147-1162, 2019 Oct.
Article in English | MEDLINE | ID: mdl-30868222

ABSTRACT

OBJECTIVES: As underlying heart diseases of right ventricular tachyarrhythmias, ARVC causes wall-motion abnormalities based on fibrofatty myocardial degeneration, while RVOT-VT and BrS are thought to lack phenotypic MR characteristics. To examine whether cardiac magnetic resonance (CMR) feature tracking (FT) in addition to ARVC objectively facilitates detection of myocardial functional impairments in RVOT-VT and BrS. METHODS: Cine MR datasets of four retrospectively enrolled, age-matched study groups [n = 65; 16 ARVC, 26 RVOT-VT, 9 BrS, 14 healthy volunteers (HV)] were independently assessed by two distinctly experienced investigators regarding myocardial function using CMR-FT. Global strain (%) and strainrate (s-1) in radial and longitudinal orientation were assessed at RVOT as well as for left (LV) and right (RV) ventricle at a basal, medial and apical section with the addition of a biventricular circumferential orientation. RESULTS: RV longitudinal and radial basal strain (%) in ARVC (- 12.9 ± 4.2; 11.4 ± 5.1) were significantly impaired compared to RVOT-VT (- 18.0 ± 2.5, p ≤ 0.005; 16.4 ± 5.2, p ≤ 0.05). Synergistically, RVOT endocardial radial strain (%) in ARVC (33.8 ± 22.7) was significantly lower (p ≤ 0.05) than in RVOT-VT (54.3 ± 14.5). For differentiation against BrS, RV basal and medial radial strain values (%) (13.3 ± 6.1; 11.8 ± 2.9) were significantly reduced when compared to HV (21.0 ± 6.9, p ≤ 0.05; 20.1 ± 6.6, p ≤ 0.005), even in case of a normal RV ejection fraction (EF) (> 45%; n = 6) (12.0 ± 2.7 vs. 20.1 ± 6.6, p ≤ 0.05). CONCLUSIONS: CMR-FT facilitates relevant differentiation in patients with right ventricular tachyarrhythmias: between ARVC against RVOT-VT and HV as well as between BrS with even a preserved EF against HV.


Subject(s)
Arrhythmogenic Right Ventricular Dysplasia/diagnosis , Brugada Syndrome/diagnosis , Electrocardiography/methods , Heart Ventricles/diagnostic imaging , Magnetic Resonance Imaging, Cine/methods , Myocardial Contraction/physiology , Ventricular Dysfunction, Right/diagnosis , Arrhythmogenic Right Ventricular Dysplasia/physiopathology , Brugada Syndrome/physiopathology , Diagnosis, Differential , Female , Follow-Up Studies , Heart Ventricles/physiopathology , Humans , Male , Middle Aged , Myocardium/pathology , Reproducibility of Results , Retrospective Studies , Ventricular Dysfunction, Right/physiopathology
2.
Clin Otolaryngol ; 40(3): 240-7, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25514878

ABSTRACT

OBJECTIVES/HYPOTHESIS: Squamous cell carcinoma of the nasal vestibule (SCCNV) is a rare tumour entity. Treatment modality, particularly indication of neck dissection, is still a controversial subject of debate. We sought to evaluate the occurrence of lymph node metastases, the prognosis and the immunohistochemical characteristics of SCCNV. STUDY DESIGN: Retrospective cohort study. METHODS: This study included 30 consecutive patients with SCCNV treated with primary tumour resection and neck dissection in cases of suspicious lymph nodes between 2003 and 2013. According to therapeutical standard adjuvant radiotherapy or chemotherapy were applied in some cases. Clinicopathological data and immunohistochemical expression of CK5/6, EGFR, Ki-67, MMP-2, MMP-9, p53 and VEGFR were analysed. RESULTS: The median follow-up period was 47.1 months. Five-year disease-free (5-year DFS) and 5-year overall survival (5-year OS) were 91.7% and 92.3%. Five-year OS in low-grade tumours (G1, G2) was 100.0%, in high-grade tumours (G3) 75.0% (P = 0.028), respectively. We did not detect any lymph node metastases in the neck dissections. Overexpression of p53 showed a trend for better 5-year OS (p53-positive 100% versus p53-negative 77.8%, n.s.). We found a positive correlation between p53 and EGFR (P = 0.0001). There was no significant relationship between the expression rates of the markers and tumour stage and grading. CONCLUSIONS: We propose no prophylactic neck dissection in small-sized SCCNV. Subtile endoscopic follow-up and periodic ultrasound examination of the cervical lymph nodes after surgical treatment are recommended. Further evaluation of the p53- and EGFR-pathways might pave the way to identify possible molecular targets in an attempt to tailor tumour management.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/surgery , Neck Dissection/methods , Nose Neoplasms/surgery , Otorhinolaryngologic Surgical Procedures/methods , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/secondary , Female , Follow-Up Studies , Humans , Immunohistochemistry , Lymphatic Metastasis , Male , Middle Aged , Nose Neoplasms/metabolism , Nose Neoplasms/pathology , Prognosis , Retrospective Studies
4.
Br J Pharmacol ; 166(2): 557-68, 2012 May.
Article in English | MEDLINE | ID: mdl-22013922

ABSTRACT

BACKGROUND AND PURPOSE Chronic heart failure (CHF) is associated with action potential prolongation and Ca(2+) overload, increasing risk of ventricular tachyarrhythmias (VT). We therefore investigated whether I(Ca) blockade was anti-arrhythmic in an intact perfused heart model of CHF. EXPERIMENTAL APPROACH CHF was induced in rabbits after 4 weeks of rapid ventricular pacing. Hearts from CHF and sham-operated rabbits were isolated and perfused (Langendorff preparation), with ablation of the AV node. VT was induced by erythromycin and low [K(+) ] (1.5mM). Electrophysiology of cardiac myocytes, with block of cation currents, was simulated by a mathematical model. KEY RESULTS Repolarization was prolonged in CHF hearts compared with sham-operated hearts. Action potential duration (APD) and overall dispersion of repolarization were further increased by erythromycin (300 µM) to block I(Kr) in CHF hearts. After lowering [K(+) ] to 1.5mM, CHF and sham hearts showed spontaneous episodes of polymorphic non-sustained VT. Additional infusion of verapamil (0.75 µM) suppressed early afterdepolarizations (EAD) and VT in 75% of sham and CHF hearts. Verapamil shortened APD and dispersion of repolarization, mainly by reducing transmural dispersion of repolarization via shortening of endocardial action potentials. Mathematical simulations showed that EADs were more effectively reduced by verapamil assuming a state-dependent block than a simple block of I(Ca) . CONCLUSIONS AND IMPLICATIONS Blockade of I(Ca) was highly effective in suppressing VT via reduction of transmural dispersion of repolarization and suppression of EAD. Such blockade might represent a novel therapeutic option to reduce risk of VT in structurally normal hearts and also in heart failure. LINKED ARTICLE This article is commented on by Stams et al., pp. 554-556 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2011.01818.x.


Subject(s)
Calcium Channel Blockers/therapeutic use , Heart Failure/drug therapy , Tachycardia, Ventricular/drug therapy , Verapamil/therapeutic use , Action Potentials/drug effects , Animals , Calcium/physiology , Calcium Channel Blockers/pharmacology , Erythromycin/pharmacology , Female , Heart/drug effects , Heart/physiology , Heart Failure/physiopathology , Models, Biological , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/physiology , Potassium Channel Blockers/pharmacology , Rabbits , Tachycardia, Ventricular/physiopathology , Verapamil/pharmacology
5.
Neurology ; 74(15): 1203-7, 2010 Apr 13.
Article in English | MEDLINE | ID: mdl-20385892

ABSTRACT

BACKGROUND: Sialorrhea affects approximately 75% of patients with Parkinson disease (PD). Sialorrhea is often treated with anticholinergics, but central side effects limit their usefulness. Glycopyrrolate (glycopyrronium bromide) is an anticholinergic drug with a quaternary ammonium structure not able to cross the blood-brain barrier in considerable amounts. Therefore, glycopyrrolate exhibits minimal central side effects, which may be an advantage in patients with PD, of whom a significant portion already experience cognitive deficits. OBJECTIVE: To determine the efficacy and safety of glycopyrrolate in the treatment of sialorrhea in patients with PD. METHODS: We conducted a 4-week, randomized, double-blind, placebo-controlled, crossover trial with oral glycopyrrolate 1 mg 3 times daily in 23 patients with PD. The severity of the sialorrhea was scored on a daily basis by the patients or a caregiver with a sialorrhea scoring scale ranging from 1 (no sialorrhea) to 9 (profuse sialorrhea). RESULTS: The mean (SD) sialorrhea score improved from 4.6 (1.7) with placebo to 3.8 (1.6) with glycopyrrolate (p = 0.011). Nine patients (39.1%) with glycopyrrolate had a clinically relevant improvement of at least 30% vs 1 patient (4.3%) with placebo (p = 0.021). There were no significant differences in adverse events between glycopyrrolate and placebo treatment. CONCLUSIONS: Oral glycopyrrolate 1 mg 3 times daily is an effective and safe therapy for sialorrhea in Parkinson disease. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that glycopyrrolate 1 mg 3 times daily is more effective than placebo in reducing sialorrhea in patients with Parkinson disease during a 4-week study.


Subject(s)
Glycopyrrolate/administration & dosage , Parkinson Disease/complications , Sialorrhea/drug therapy , Sialorrhea/etiology , Aged , Double-Blind Method , Drug Administration Schedule , Female , Humans , Intention to Treat Analysis , Male , Middle Aged , Muscarinic Antagonists/administration & dosage , Surveys and Questionnaires , Treatment Outcome
6.
Surgery ; 142(4): 546-53; discussion 553-5, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17950347

ABSTRACT

BACKGROUND: Cost analysis after laparoscopic colectomy has been examined, although reports evaluating the effects of laparoscopy on hospital operating margin are lacking. We compared several cost/revenue measures, including hospital operating margin, between open and laparoscopic colectomies at an academic center. METHODS: Our cost-accounting database was queried for laparoscopic partial (LPC) and total colectomies (LTC), and open partial (OPC) and total colectomies (OTC) to analyze net revenue, total costs, and total hospital operating margin over a 4-year period. Laparoscopic and open colectomy cases were compared, with mean operating margin as the primary outcome. RESULTS: From July, 2002 through May, 2006, 842 patients were included for analysis with 138 undergoing laparoscopic colectomy. Net revenue was higher in the LTC group compared with open (US dollars 30,300 vs US dollars 26,800 [P = .02]), and lower in the LPC group (US dollars 15,300 vs US dollars 21,300 open [P < .0001]). Total costs were reduced in both the LPC and LTC groups compared with open [US dollars 11,700 vs US dollars 17,600 [P < .0001] and US dollars 18,000 vs US dollars 19,400 [P = .0019], respectively). LPC resulted in a similar HOM (US dollars 3,602) compared with OPC (US dollars 3,647; P = .35). LTC resulted in a higher HOM (US dollars 12,300) compared with OTC (US dollars 7,400; P = .02). CONCLUSIONS: LTC generates a significantly higher hospital operating margin than an OTC, although the margins are similar for LPC and OPC.


Subject(s)
Academic Medical Centers/economics , Colectomy/economics , Digestive System Surgical Procedures/economics , Laparoscopy/economics , Surgery Department, Hospital/economics , Adolescent , Adult , Aged , Aged, 80 and over , Cost-Benefit Analysis , Costs and Cost Analysis , Female , Hospital Costs , Humans , Length of Stay/economics , Male , Middle Aged
7.
Article in English | MEDLINE | ID: mdl-10913225

ABSTRACT

We investigated whether supplementation with arachidonic acid (20:4 omega 6; AA), or a combination of AA and docosahexaenoic acid (22:6 omega 3; DHA) would affect human milk polyunsaturated fatty acid (PUFA) composition. Ten women were daily supplemented with 300 mg AA, eight with 300 mg AA, 110 mg eicosapentaenoic acid (20:5 omega 3; EPA) and 400 mg DHA, for one week and eight women served as unsupplemented controls. Milk samples were collected on days 0, 1 and 7. The fatty acid composition of the milk was analyzed by capillary gas chromatography with flame ionisation detection. Supplementation with AA alone had no effect on breastmilk AA, but tended to reduce EPA and DHA levels. Administration of a combination of AA, EPA and DHA tended to increase both milk AA and long chain PUFA (LCPUFA)omega 3 content. A larger simultaneous increase of milk AA, DHA and EPA than observed in the present study can probably be accomplished by the use of a combination of a lower LCPUFA omega 6/LCPUFA omega 3 ratio and higher AA, EPA and DHA dosages.


Subject(s)
Arachidonic Acid/administration & dosage , Docosahexaenoic Acids/administration & dosage , Eicosapentaenoic Acid/administration & dosage , Fatty Acids, Unsaturated/analysis , Milk, Human/chemistry , Adult , Arachidonic Acid/analysis , Dietary Fats, Unsaturated/administration & dosage , Dietary Fats, Unsaturated/analysis , Dietary Supplements , Docosahexaenoic Acids/analysis , Eicosapentaenoic Acid/analysis , Female , Humans , Statistics, Nonparametric
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