Genotoxicity of hormonal steroids Joosten, H.F.P; van Acker, F.A.A; van den Dobbelsteen, D.J ...
Toxicology letters,
06/2004, Letnik:
151, Številka:
1
Journal Article
Recenzirano
Hormonal steroids have a widespread use in medicine and their side effects are continuously debated. The possible genotoxic activity of steroids has been the subject of many investigations.
The ...natural estrogens estradiol, estrone and estriol are generally negative in the ICH core battery of tests, but several positive results have been obtained when using additional endpoints of genotoxicity. The genotoxic activity of the 4-hydroxy metabolites of estradiol and estrone is well established. The synthetic steroidal estrogens have a comparable profile of negative and positive test results. Cyproterone acetate and some of its analogues have a special position within the group of progestins. Their genotoxic potential has been established. Other progestins are generally negative in the routine tests. Anti-glucocorticoids, anti-progestins, corticosteroids, androgens, anabolics and anti-androgens appear to be devoid of genotoxic activities.
The genotoxic potential of estradiol, estrone and cyproterone acetate with its analogues may play no role under normal physiological and therapeutic conditions. The metabolic conditions that are needed for the formation of DNA-reactive metabolites and oxygen radicals may not be present in humans. Epidemiological cancer data seem to support this view.
The importance of thresholds in the dose–effect-relationship of genotoxicity data and their use in risk assessment is discussed.
Classic anatomical dissection of 150 hearts from adults aged 18–80 years was performed. The sinoatrial (SA) node artery was most frequently a large atrial branch of the right coronary artery (63%), ...arising at a mean distance of 1.2 cm (range 0.2–2.2 cm) from its beginning, with a mean external diameter of 1.7 mm (range 1–3 mm). In 37% of cases the SA node artery was a branch of the left coronary artery or one of its branches, with an initial mean external diameter of 2.2 mm (range 2–3 mm). The origin of the SA node artery was not related to coronary arterial dominance. The atrioventricular (AV) node artery was the first and longest inferior septal perforating branch of the right (90%) or left (10%) coronary artery, arising from the U- or V-shaped segment of the corresponding artery at the level of the crux cordis. Mean external diameter was 2 mm (range 1–3.5 mm). The origin of the AV node artery was dependent on coronary arterial dominance. Identification of the anatomical variants of the arterial blood supply to the SA and AV nodes may help in overcoming potential difficulties in treating arrhythmias and in mitral valve surgery.
This study investigated whether the type of surgical procedure used to treat breast cancer (mastectomy versus breast-conserving lumpectomy) had any effect on the quality of life and social status of ...women. The prospective analysis included 382 women newly diagnosed with non-metastatic breast cancer who had undergone a surgical intervention for breast carcinoma at our institution: 198 patients had undergone mastectomy with axillary lymphadenectomy and 184 patients had undergone breast-conserving lumpectomy with local axillary lymphadenectomy. The post-mastectomy women reported significantly more financial problems, a lowered social status and more physical symptoms compared with the breast-conserving post-lumpectomy patients. The patients that underwent lumpectomy were more satisfied with their body image and their sexual life. Since the adverse financial effects of wage loss can significantly decrease a patient's quality of life, this study indicates that postmastectomy patients in particular need to be protected more effectively against a decline in their social status.
This study evaluated the occurrence and frequency of the anatomical variations of the origin and course of the posterior intercostal arteries (PIA) in 44 human cadavers. During a classical anatomical ...dissection of each cadaver an anomalous course of the PIA, defined as a thoracic vertebral artery, was found in six (14%) individuals. Every dorsally coursing PIA was taken into account, regardless of its origin, and their different origins and course were described. A specific dorsal course for the PIA was found in nine cases, which was bilateral in two cases. The variations that were found and that have been schematically presented will provide new information about the anatomical variations of the PIA. Consideration of the potential for anatomical variation of the PIA is important in vascular and thoracic surgery and in diagnostic and interventional radiology such as spinal angiography.
Collection of toxicokinetic data has become a routine practice during the last 15 years in most general toxicity studies on pharma. It enables the correlation of pathological changes with the plasma ...concentration of drugs and/or their metabolites. This overview summarizes the use of the toxicokinetic data from the perspective of the toxicologic pathologist.
During operative treatment for ovarian tumours assistance is frequently required to make decisions regarding malignancy status and the extent of the ensuing procedure. Intra-operative frozen section ...analysis may be useful, provided there is adequate acquaintance with the correlation between using frozen sections and permanent histopathological sections for diagnosis at the institution where the operation is being undertaken. This retrospective study aimed to determine this correlation. Findings from 131 intraoperative frozen sections were compared with the subsequent diagnosis from permanent histopathological sections for women with benign, borderline and malignant ovarian tumours at the Maribor Teaching Hospital (now the University Clinical Centre Maribor) between 1 January 1993 and 31 December 2001. Frozen-section findings corresponded to histopathological findings in 84.7% of cases, with 15.3% false-negative and no false-positive results. For benign, borderline and malignant ovarian tumours, sensitivity was 100.0%, 76.1% and 89.0%, respectively, and specificity was 90.6%, 90.6% and 100.0%, respectively. The majority of errors occurred in diagnosing mucinous borderline tumours. Precise preoperative diagnosis is extremely important in the treatment of ovarian tumours.
Classic anatomical dissection of 150 heart specimens from adults aged 18 − 80 years was performed. Anatomical variations were studied in: (i) the position of the ostium of the left coronary artery; ...(ii) the angle between the proximal segment of the left coronary artery and the longitudinal axis of the aorta and between the circumflex and the anterior descending branches; (iii) the angle between the anterior descending artery and the diagonal branches, and between the diagonal and circumflex branches in trifurcation of the left coronary artery; (iv) the position of the ostium of the right coronary artery in the right coronary sinus of Valsalva; (v) the angle between the initial part of the right coronary artery and the logitudinal axis of the aorta; and (vi) the position of the initial part of the left coronary artery relative to the coronary groove. Knowledge of and the ability to recognize and identify the variety of sites of origin of coronary arteries, aortocoronary angles and angles of division of the left coronary artery of the human heart may help to overcome potential difficulties in cardiosurgical procedures, such as aortic valve replacement and reinsertion of coronary arteries.
Classic anatomical dissection of 150 heart specimens from adults aged 18–80 years was performed. The Thebesian valve was absent in 20% of cases and, in these, 4% had a large ostial valve of the ...middle cardiac vein in front of the coronary sinus ostium. Fibres of Chiari were found in 10% of cases. Ostia of the middle cardiac vein, posterior veins of the left ventricle, small cardiac vein and deep cardiac veins were present in the distal 10 mm of the coronary sinus. Some samples had ostial and/or parietal valves or antivalves that sometimes contained muscular fibres. Distal accessory parietal valves (2%) and antivalves (1%) of the coronary sinus wall were found at a distance of 4–7 mm from its ostium. The frequency and variability of anatomical structures in the area of the coronary sinus ostium probably influence the haemodynamics of this area. Knowledge of and being able to identify these anatomical variations may help in identifying and overcoming potential difficulties in treating arrythmias and in cardiosurgery.
Abstract
Background
Myocardial infarction (MI) remains the most common cause of heart failure (HF). Data on sex-related critical state in patients with MI who underwent PCI and their long-term ...outcome, are missing.
Purpose
We evaluated whether there is a sex difference in critical state and if sex is associated with long-term survival in these patients.
Methods
We defined critical state as cardiogenic shock and/or mechanical ventilation and/or intra-aortic balloon pump and/or ejection fraction≤30%. We analyzed data on 5669 patients with MI treated with percutaneous interventions (PCI). The criteria for critical state were fulfilled by 539 (9.5%) patients, of whom 172 (31.9%) were women. Long-term mortality was observed. The median follow-up time was 5.0 (25th, 75th percentile: 3,8) years. Data were analyzed using descriptive statistics.
Results
The incidence of critical state was similar in both sexes 172 (9.8%) women compared to 367 (9.4%) men. The women were older, suffered more diabetes and renal dysfunction, presented more often in cardiogenic shock, and had a higher maximal troponin/body surface area level. After adjustment, female sex was associated with critical state (adjusted OR 1.38; 95% CI 1.07 to 1.77; p=0.013). However, similar unadjusted long-term mortality was observed 111 (64.5%) of women died compared to 244 (66.5%) men, p=0.70. Furthermore, after adjustment for potential confounders, female sex was associated with a 24% lower risk of dying in the long term (adjusted HR 0.76; 95% CI 0.58 to 0.98; p=0.037) compared to men (Figure 1). Other predictors of long-term mortality in patients with critical state were age, hyperlipidemia, renal dysfunction, and dual antiplatelet therapy.
Figure 1
Conclusion
Female sex was associated with critical state. However, the unadjusted long-term mortality was similar in both sexes. In addition, female sex was associated with better long-term survival in patients with critical state. Further investigation is required to answer these associations.
Aims
To evaluate how recommendations of European guidelines regarding pharmacological and non‐pharmacological treatments for heart failure (HF) are adopted in clinical practice.
Methods and results
...The ESC‐HF Long‐Term Registry is a prospective, observational study conducted in 211 Cardiology Centres of 21 European and Mediterranean countries, members of the European Society of Cardiology (ESC). From May 2011 to April 2013, a total of 12 440 patients were enrolled, 40.5% with acute HF and 59.5% with chronic HF. Intravenous treatments for acute HF were heterogeneously administered, irrespective of guideline recommendations. In chronic HF, with reduced EF, renin–angiotensin system (RAS) blockers, beta‐blockers, and mineralocorticoid antagonists (MRAs) were used in 92.2, 92.7, and 67.0% of patients, respectively. When reasons for non‐adherence were considered, the real rate of undertreatment accounted for 3.2, 2.3, and 5.4% of the cases, respectively. About 30% of patients received the target dosage of these drugs, but a documented reason for not achieving the target dosage was reported in almost two‐thirds of them. The more relevant reasons for non‐implantation of a device, when clinically indicated, were related to doctor uncertainties on the indication, patient refusal, or logistical/cost issues.
Conclusion
This pan‐European registry shows that, while in patients with acute HF, a large heterogeneity of treatments exists, drug treatment of chronic HF can be considered largely adherent to recommendations of current guidelines, when the reasons for non‐adherence are taken into account. Observations regarding the real possibility to adhere fully to current guidelines in daily clinical practice should be seriously considered when clinical practice guidelines have to be written.
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