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1.
S Afr J Surg ; 60(4): 319-320, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36477068

ABSTRACT

SUMMARY: This report describes acute gallbladder torsion in a previously healthy 16-year-old male. The patient presented with acute right-sided abdominal pain in keeping with acute appendicitis and was taken for a diagnostic laparoscopy where an intraoperative diagnosis of gallbladder torsion was made. This case highlights a very rare surgical presentation in an uncommon patient profile. It highlights the benefit of diagnostic laparoscopy in a resource-constrained facility.


Subject(s)
Gallbladder , Humans , Adolescent , Gallbladder/diagnostic imaging , Gallbladder/surgery
2.
J Eur Acad Dermatol Venereol ; 36(10): 1751-1757, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35470483

ABSTRACT

BACKGROUND: Chlormethine gel is a skin-directed therapy used for patients with mycosis fungoides (MF) that showed a favourable risk/benefit profile in a randomized clinical trial. Currently, data on chlormethine gel use in real-world settings are limited. OBJECTIVES: The aim of this study was to assess safety and efficacy of chlormethine gel treatment in patients treated during daily clinical practice and investigate associations between response and disease stage, lesion type, mono- or combination therapy, and occurrence of dermatitis. METHODS: Clinical data from patients using chlormethine gel from three sites in Greece were analysed. Efficacy was assessed through modified Severity-Weighted Assessment Tool (mSWAT) scores. Safety assessments included analysis of the occurrence and severity of dermatitis. The Skindex-29 questionnaire was used for quality-of-life assessments. RESULTS: Fifty-eight patients were included. The overall response rate (ORR) increased from 37.9% at month 1 to 80.8% at month 9. For 64.2% of patients, response was maintained for at least 4 months (ORR4). At month 3, a higher ORR was seen for patients with patches (69.7%) than patients with plaques/tumours (both 15.2%). A higher ORR4 was observed for patients with early- vs late-stage disease (71.4% vs. 36.4%) and patients on mono- vs combination therapy (75% vs. 47.6%). Dermatitis was observed in the majority of patients (72.4%), but the presence or severity of dermatitis was not directly correlated with treatment response. Both mSWAT and Skindex-29 scores decreased significantly during treatment, and changes in these scores from baseline to month 6 showed a positive correlation (r = 0.55, P = 0.026). CONCLUSIONS: Chlormethine gel was effective for the treatment of skin lesions in patients with early- and late-stage MF in clinical practice. Response rates increased over time, indicating that continued treatment with the gel is important. Dermatitis may be managed by reducing the treatment frequency; the occurrence of dermatitis did not affect the response to treatment.


Subject(s)
Mycosis Fungoides , Skin Diseases , Skin Neoplasms , Combined Modality Therapy , Humans , Mechlorethamine/adverse effects , Mycosis Fungoides/pathology , Skin Diseases/drug therapy , Skin Neoplasms/pathology
4.
Br J Dermatol ; 184(4): 722-730, 2021 04.
Article in English | MEDLINE | ID: mdl-32479678

ABSTRACT

BACKGROUND: The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is a prospective analysis of an international database. Here we examine front-line treatments and quality of life (QoL) in patients with newly diagnosed mycosis fungoides (MF). OBJECTIVES: To identify (i) differences in first-line approaches according to tumour-nodes-metastasis-blood (TNMB) staging; (ii) parameters related to a first-line systemic approach and (iii) response rates and QoL measures. METHODS: In total, 395 newly diagnosed patients with early-stage MF (stage IA-IIA) were recruited from 41 centres in 17 countries between 1 January 2015 and 31 December 2018 following central clinicopathological review. RESULTS: The most common first-line therapy was skin-directed therapy (SDT) (322 cases, 81·5%), while a smaller percentage (44 cases, 11·1%) received systemic therapy. Expectant observation was used in 7·3%. In univariate analysis, the use of systemic therapy was significantly associated with higher clinical stage (IA, 6%; IB, 14%; IIA, 20%; IA-IB vs. IIA, P < 0·001), presence of plaques (T1a/T2a, 5%; T1b/T2b, 17%; P < 0·001), higher modified Severity Weighted Assessment Tool (> 10, 15%; ≤ 10, 7%; P = 0·01) and folliculotropic MF (FMF) (24% vs. 12%, P = 0·001). Multivariate analysis demonstrated significant associations with the presence of plaques (T1b/T2b vs. T1a/T2a, odds ratio 3·07) and FMF (odds ratio 2·83). The overall response rate (ORR) to first-line SDT was 73%, while the ORR to first-line systemic treatments was lower (57%) (P = 0·027). Health-related QoL improved significantly both in patients with responsive disease and in those with stable disease. CONCLUSIONS: Disease characteristics such as presence of plaques and FMF influence physician treatment choices, and SDT was superior to systemic therapy even in patients with such disease characteristics. Consequently, future treatment guidelines for early-stage MF need to address these issues.


Subject(s)
Mycosis Fungoides , Skin Neoplasms , Humans , Mycosis Fungoides/pathology , Mycosis Fungoides/therapy , Neoplasm Staging , Prognosis , Prospective Studies , Quality of Life , Skin Neoplasms/pathology , Skin Neoplasms/therapy
5.
J Eur Acad Dermatol Venereol ; 34(11): 2534-2540, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32364303

ABSTRACT

BACKGROUND: Retinoids have long been used in the treatment of cutaneous T-cell lymphomas. However, data on acitretin use for mycosis fungoides (MF) are very limited. OBJECTIVES: To evaluate treatment outcomes of acitretin in patients with MF attending three academic referral centres in different regions of Greece. METHODS: Data on effectiveness, safety and drug survival of acitretin as monotherapy or as adjuvant regimen were collected in a multicentre, register-based, retrospective study. RESULTS: Overall, 128 patients (64.8% male; mean age at MF diagnosis 59.7 years) were included. Folliculotropic MF was present in 24 (18.8%) cases. Most patients (n = 118; 92.2%) had early-stage disease (≤IIA) at acitretin initiation. In all, 28 (21.9%) patients received acitretin monotherapy, while 100 (78.1%) subjects on acitretin concomitantly received phototherapy (n = 65; 50.8%) or topical steroids (n = 27; 21.1%). Acitretin was given as a first-line agent in 73 (57%) cases. A 77.3% overall response rate was noted: 44.5% and 32.8% for complete and partial responses, respectively. Acitretin was more effective as first-line than as a subsequent agent (P = 0.008). A trend towards better response was observed in the combination arm compared to patients receiving acitretin alone (P = 0.056). Median time to best response was 6.9 months (IQR 4.4-9.4); median duration of response was 23.7 months (IQR 11.9-35.4). Overall, the mean length of all treatment patterns was 569 days (SD 718.8). Therapy was discontinued in 5 (3.9%) cases due to drug intolerance. Adverse effects were recorded in 62 (48.4%) cases with dyslipidaemia (n = 31; 24.2%), xerosis (n = 24; 18.6%) and hair loss (n = 10; 7.8%) being the most commonly recorded. CONCLUSIONS: Acitretin, either alone or as adjuvant, showed a stable long-term effectiveness in this cohort, especially when used in the first-line setting. This RAR-selective agonist may serve as an attractive option for treatment of MF and should be further evaluated.


Subject(s)
Mycosis Fungoides , Skin Neoplasms , Acitretin/therapeutic use , Female , Greece , Humans , Male , Mycosis Fungoides/drug therapy , Retrospective Studies , Skin Neoplasms/drug therapy , Treatment Outcome
6.
Physiol Res ; 68(5): 867-871, 2019 10 25.
Article in English | MEDLINE | ID: mdl-31424250

ABSTRACT

Endothelin alters central sympathetic responses, but the resultant effects on arrhythmogenesis are unknown. We examined ventricular tachyarrhythmias after endothelin receptor-A blockade in the brain of Wistar rats with acute myocardial infarction. For this aim, BQ-123 (n=6) or phosphate-buffered saline (n=6) were injected intracerebroventricularly. After 10 min, the left coronary artery was ligated, followed by implantation of telemetry transmitters. Electrocardiography and voluntary activity (as a surrogate of acute left ventricular failure) were continuously monitored for 24 h. Infarct-size was similar in the two groups. There were fewer episodes of ventricular tachyarrhythmias of shorter average duration in treated rats, leading to markedly shorter total duration (12.3+/-8.9 s), when compared to controls (546.2+/-130.3 s). Voluntary activity increased in treated rats during the last hours of recording, but bradyarrhythmic episodes were comparable between the two groups. Endothelin receptor-A blockade in the brain of rats decreases the incidence of ventricular tachyarrhythmias post-ligation, without affecting bradyarrhythmic episodes. These findings call for further research on the pathophysiologic role of endothelin during acute myocardial infarction.


Subject(s)
Cerebral Ventricles/drug effects , Endothelin A Receptor Antagonists/administration & dosage , Myocardial Infarction/drug therapy , Peptides, Cyclic/administration & dosage , Receptor, Endothelin A/drug effects , Tachycardia, Ventricular/prevention & control , Ventricular Premature Complexes/prevention & control , Animals , Cerebral Ventricles/metabolism , Cerebral Ventricles/physiopathology , Disease Models, Animal , Injections, Intraventricular , Myocardial Infarction/complications , Myocardial Infarction/metabolism , Myocardial Infarction/physiopathology , Rats, Wistar , Receptor, Endothelin A/metabolism , Tachycardia, Ventricular/etiology , Tachycardia, Ventricular/metabolism , Tachycardia, Ventricular/physiopathology , Ventricular Premature Complexes/etiology , Ventricular Premature Complexes/metabolism , Ventricular Premature Complexes/physiopathology
7.
BJOG ; 126(4): 493-499, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30223309

ABSTRACT

OBJECTIVE: To analyse the outcome of referrals for external cephalic version (ECV). DESIGN: Retrospective cohort study of prospectively collected data. SETTING: Major university hospital, UK. SAMPLE: Women with non-cephalic presentation at term and no prior caesarean, referred to a specialist clinic. METHODS: Details of referrals, ECV attempts, and perinatal outcomes were prospectively collected and analysed. Multivariate binary logistic regression models were created to determine independent predictors of ECV success, reversion, and spontaneous version. MAIN OUTCOME MEASURES: External cephalic version success rates, predictors of success and cephalic presentation at birth, and perinatal outcomes. RESULTS: Three thousand eight had confirmed breech presentation; 2614 women underwent ECV. Ineligibility for ECV occurred in 117 breech presentations (3.9%), and 297 eligible women (10.2%) declined it. ECV was successful in 1280 (49.0%, 95% CI 47.0-50.9%) (40% in nulliparous women; 64% in others); 1234 (97.3%) were cephalic at birth. Spontaneous version after failure occurred in 4.3% and was more common in multiparas (aOR 2.47, 95% CI 1.43-4.26) and those with a posterior fetal back (aOR 6.09, 95% CI 1.90-19.53). Reversion after successful ECV occurred in 2.2%. In women with a successful ECV whose fetus remained cephalic at birth, 85.7% delivered vaginally. The corrected perinatal mortality of the ECV cohort was 0.12%. CONCLUSION: External cephalic version has a low complication rate and is effective for most breech presentations, enabling vaginal birth and avoiding caesarean section. TWEETABLE ABSTRACT: External cephalic version can safely be performed with most breech presentations.


Subject(s)
Breech Presentation/therapy , Delivery, Obstetric/statistics & numerical data , Version, Fetal/statistics & numerical data , Adult , Delivery, Obstetric/methods , Female , Humans , Logistic Models , Pregnancy , Retrospective Studies , Term Birth , Treatment Outcome , United Kingdom , Vagina
8.
S Afr J Surg ; 55(2): 14-17, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28876618

ABSTRACT

BACKGROUND: Complex (perforated or gangrenous) appendicitis has a high rate of morbidity in South Africa. METHOD: The study retrospectively reviewed results from January 2013 to December 2015 at Paarl Hospital in the Western Cape province. All patients who had their appendices surgically removed due to suspected appendicitis and who had preoperative results for CRP and WCC were included. Using the area under the Receiver Operated Characteristics curve we compared the inflammatory markers of 2 groups with histologically proven appendicitis: those with complex (perforated or gangrenous appendix) and those with uncomplicated appendicitis (inflamed appendix). Youden's J statistic was used to determine the optimal cut-off value above which complex appendicitis would be the most likely diagnosis. RESULTS: A total of 591 patients were identified, 385 had results for both WCC and CRP. CRP (AUC 72%) proved to be a fair and WCC (AUC 58%) a poor predictor of complex appendicitis. Cut-off values for CRP and WCC were found to be 215 mg/l and 16.80 109 cells/l respectively. At these threshold values CRP (sensitivity 51.4%, specificity 85.7%, p-value < 0.001, positive predictive value 80.2%, negative predictive value 61%, positive likelihood ratio 3.6 and diagnostic odds ratio 6.35) proved to be much better than WCC (sensitivity 43%, specificity 73.8%, p-value = 0.022, positive predictive value 64.9%, negative predictive value 53.4%, positive likelihood ratio 1.64 and diagnostic odds ratio 2.11) in predicting complex appendicitis. CONCLUSION: CRP is superior to WCC in the differentiation between uncomplicated and complex appendicitis. Using a cut-off value of CRP 215 mg/l is statistically significant in diagnosing complex appendicitis. This value should be used cautiously as many more studies are needed to confirm these findings.


Subject(s)
Appendicitis/diagnosis , C-Reactive Protein/metabolism , Severity of Illness Index , Adolescent , Adult , Aged , Appendicitis/blood , Appendicitis/complications , Appendicitis/pathology , Biomarkers/blood , Child , Child, Preschool , Female , Humans , Leukocyte Count , Male , Middle Aged , ROC Curve , Retrospective Studies , Sensitivity and Specificity , Young Adult
9.
Phys Med Biol ; 62(18): 7532-7555, 2017 Sep 05.
Article in English | MEDLINE | ID: mdl-28796643

ABSTRACT

Detector-, field size- and machine-specific correction factors are required for precise dosimetry measurements in small and non-standard photon fields. In this work, Monte Carlo (MC) simulation techniques were used to calculate the [Formula: see text] and [Formula: see text] correction factors for a series of ionization chambers, a synthetic microDiamond and diode dosimeters, used for reference and/or output factor (OF) measurements in the Gamma Knife Perfexion photon fields. Calculations were performed for the solid water (SW) and ABS plastic phantoms, as well as for a water phantom of the same geometry. MC calculations for the [Formula: see text] correction factors in SW were compared against corresponding experimental results for a subset of ionization chambers and diode detectors. Reference experimental OF data were obtained through the weighted average of corresponding measurements using TLDs, EBT-2 films and alanine pellets. [Formula: see text] values close to unity (within 1%) were calculated for most of ionization chambers in water. Greater corrections of up to 6.0% were observed for chambers with relatively large air-cavity dimensions and steel central electrode. A phantom correction of 1.006 and 1.024 (breaking down to 1.014 from the ABS sphere and 1.010 from the accompanying ABS phantom adapter) were calculated for the SW and ABS phantoms, respectively, adding up to [Formula: see text] corrections in water. Both measurements and MC calculations for the diode and microDiamond detectors resulted in lower than unit [Formula: see text] correction factors, due to their denser sensitive volume and encapsulation materials. In comparison, higher than unit [Formula: see text] results for the ionization chambers suggested field size depended dose underestimations (being significant for the 4 mm field), with magnitude depending on the combination of contradicting phenomena associated with volume averaging and electron fluence perturbations. Finally, the presence of 0.5 mm air-gap between the diodes' frontal surface and their phantom-inserts may considerably influence OF measurements, reaching 4.6% for the Razor diode.


Subject(s)
Monte Carlo Method , Phantoms, Imaging , Photons/therapeutic use , Radiosurgery/methods , Electrons , Humans , Radiometry/methods , Water
10.
Br J Dermatol ; 176(5): 1321-1330, 2017 May.
Article in English | MEDLINE | ID: mdl-27552962

ABSTRACT

BACKGROUND: Mycosis fungoides (MF) is an indolent cutaneous lymphoma with excellent prognosis at early stages and much poorer outcome during disease progression. Old age, male sex and folliculotropism have been proposed as relevant prognostic factors; however, their exact effect remains debatable. OBJECTIVES: To evaluate MF prognostic indicators and survival rates in a Greek population. METHODS: Prognostic variables affecting survival rates were studied in 473 patients with MF diagnosed and treated by two academic referral centres in Greece. Kaplan-Meier estimates were used to determine survival rates and progression. The Cox proportional hazards regression model was used to assess prognostic factors. RESULTS: The mean age of diagnosis was 61·7 years (SD 16·33). Five-year disease-specific survival was 96% in patients with stage IA disease and 52% in patients with stage IIB disease. Univariate analysis certified that large-cell transformation, clonal rearrangements of the TCR gene, severe pruritus and presence of plaques were the most important prognostic factors. Folliculotropism altered disease progression only in patients with early-stage disease. The application of the Cutaneous Lymphoma International Prognostic Index (CLIPI) on our late-stage group failed to provide reliable evidence. The current Cutaneous Lymphoma International Consortium (CLIC) prognostic index can efficiently distinguish a low-risk from a high-risk group of patients. Tumour-Node-Metastasis-Blood (TNMB) staging was the most important prognostic factor for survival rates in multivariate analysis. CONCLUSIONS: In our study we validated the current prognostic indicators for MF in a Greek population and identified new potential prognostic factors for survival outcome. Our findings contribute to the ongoing investigation of prognostic indicators of MF, further validation of which is highly needed through prospective studies and among different populations.


Subject(s)
Mycosis Fungoides/mortality , Skin Neoplasms/mortality , Disease Progression , Female , Greece/epidemiology , Humans , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Middle Aged , Prognosis , Sex Distribution , Sexism , Survival Rate
11.
Phys Med Biol ; 61(19): 6993-7011, 2016 10 07.
Article in English | MEDLINE | ID: mdl-27648985

ABSTRACT

This work provides characterization of system-related geometric distortions present in MRIs used in Gamma Knife (GK) stereotactic radiosurgery (SRS) treatment planning. A custom-made phantom, compatible with the Leksell stereotactic frame model G and encompassing 947 control points (CPs), was utilized. MR images were obtained with and without the frame, thus allowing discrimination of frame-induced distortions. In the absence of the frame and following compensation for field inhomogeneities, measured average CP disposition owing to gradient nonlinearities was 0.53 mm. In presence of the frame, contrarily, detected distortion was greatly increased (up to about 5 mm) in the vicinity of the frame base due to eddy currents induced in the closed loop of its aluminum material. Frame-related distortion was obliterated at approximately 90 mm from the frame base. Although the region with the maximum observed distortion may not lie within the GK treatable volume, the presence of the frame results in distortion of the order of 1.5 mm at a 7 cm distance from the center of the Leksell space. Additionally, severe distortions observed outside the treatable volume could possibly impinge on the delivery accuracy mainly by adversely affecting the registration process (e.g. the position of the lower part of the N-shaped fiducials used to define the stereotactic space may be miss-registered). Images acquired with a modified version of the frame developed by replacing its front side with an acrylic bar, thus interrupting the closed aluminum loop and reducing the induced eddy currents, were shown to benefit from relatively reduced distortion. System-related distortion was also identified in patient MR images. Using corresponding CT angiography images as a reference, an offset of 1.1 mm was detected for two vessels lying in close proximity to the frame base, while excellent spatial agreement was observed for a vessel far apart from the frame base.


Subject(s)
Image Processing, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Magnetic Resonance Imaging/methods , Models, Theoretical , Phantoms, Imaging , Radiosurgery/instrumentation , Radiotherapy Planning, Computer-Assisted/methods , Humans , Polymethyl Methacrylate , Radiosurgery/methods
12.
Mol Hum Reprod ; 22(8): 877-89, 2016 08.
Article in English | MEDLINE | ID: mdl-27235325

ABSTRACT

STUDY HYPOTHESIS: Myometrial explants represent a superior model compared with cell culture models for the study of human myometrial progesterone (P4) signalling in parturition. STUDY FINDING: Gene expression analysis showed myometrial explants closely resemble the in vivo condition and the anti-inflammatory action of P4 is not lost with labour onset. WHAT IS KNOWN ALREADY: Circulating P4 levels decline before the onset of parturition in most animals, but not in humans. This has led to the suggestion that there is a functional withdrawal of P4 action at the myometrial level prior to labour onset. However, to date, no evidence of a loss of P4 function has been provided, with studies hampered by a lack of a physiologically relevant model. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Myometrial biopsies obtained at Caesarean section were dissected into explants after a portion was immediately snap frozen (t = 0). Microarray analysis was used to compare gene expression of t = 0 with paired (i) explants, (ii) passage 4 myometrial cell cultures or (iii) the hTERT myometrial cell line. Western blotting and chemokine/cytokine assays were used to study P4 signalling in myometrial explants. MAIN RESULTS AND THE ROLE OF CHANCE: Gene expression comparison of t = 0 to the three models demonstrated that explants more closely resemble the in vivo status. At the protein level, explants maintain both P4 receptor (PR) and glucocorticoid receptor (GR) levels versus t = 0 whereas cells only maintain GR levels. Additionally, treatment with 1 µM P4 led to a reduction in interleukin-1 (IL-1) ß-driven cyclooxygenase-2 in explants but not in cells. P4 signalling in explants was PR-mediated and associated with a repression of p65 and c-Jun phosphorylation. Furthermore, the anti-inflammatory action of P4 was maintained after labour onset. LIMITATIONS/REASONS FOR CAUTION: There is evidence of basal inflammation in the myometrial explant model. WIDER IMPLICATIONS OF THE FINDINGS: Myometrial explants constitute a novel model to study P4 signalling in the myometrium and can be used to further elucidate the mechanisms of P4 action in human labour. LARGE SCALE DATA: Data deposited at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=gvmpggkurbgxfqf&acc=GSE77830. STUDY FUNDING AND COMPETING INTEREST: This work was supported by grants from the Joint Research Committee of the Westminster Medical School Research Trust, Borne (No. 1067412-7; a sub-charity of the Chelsea and Westminster Health Charity) and the Imperial NIHR Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS or the Department of Health. The authors have no conflict of interest.


Subject(s)
Myometrium/metabolism , Progesterone/metabolism , Cell Line , Cyclooxygenase 2/metabolism , Female , Humans , In Vitro Techniques , Receptors, Glucocorticoid/metabolism , Receptors, Progesterone/metabolism , Reverse Transcriptase Polymerase Chain Reaction
13.
Phys Med Biol ; 61(3): 1182-203, 2016 Feb 07.
Article in English | MEDLINE | ID: mdl-26788618

ABSTRACT

This work presents a comprehensive Monte Carlo (MC) simulation model for the Gamma Knife Perfexion (PFX) radiosurgery unit. Model-based dosimetry calculations were benchmarked in terms of relative dose profiles (RDPs) and output factors (OFs), against corresponding EBT2 measurements. To reduce the rather prolonged computational time associated with the comprehensive PFX model MC simulations, two approximations were explored and evaluated on the grounds of dosimetric accuracy. The first consists in directional biasing of the (60)Co photon emission while the second refers to the implementation of simplified source geometric models. The effect of the dose scoring volume dimensions in OF calculations accuracy was also explored. RDP calculations for the comprehensive PFX model were found to be in agreement with corresponding EBT2 measurements. Output factors of 0.819 ± 0.004 and 0.8941 ± 0.0013 were calculated for the 4 mm and 8 mm collimator, respectively, which agree, within uncertainties, with corresponding EBT2 measurements and published experimental data. Volume averaging was found to affect OF results by more than 0.3% for scoring volume radii greater than 0.5 mm and 1.4 mm for the 4 mm and 8 mm collimators, respectively. Directional biasing of photon emission resulted in a time efficiency gain factor of up to 210 with respect to the isotropic photon emission. Although no considerable effect on relative dose profiles was detected, directional biasing led to OF overestimations which were more pronounced for the 4 mm collimator and increased with decreasing emission cone half-angle, reaching up to 6% for a 5° angle. Implementation of simplified source models revealed that omitting the sources' stainless steel capsule significantly affects both OF results and relative dose profiles, while the aluminum-based bushing did not exhibit considerable dosimetric effect. In conclusion, the results of this work suggest that any PFX simulation model should be benchmarked in terms of both RDP and OF results.


Subject(s)
Radiosurgery/methods , Radiotherapy Planning, Computer-Assisted/methods , Monte Carlo Method , Radiometry/methods
14.
Radiat Prot Dosimetry ; 172(4): 409-415, 2016 Dec.
Article in English | MEDLINE | ID: mdl-26656074

ABSTRACT

The aim of the present study is the estimation of radiation burden during liver chemoembolisation procedures. Organ dose and effective dose conversion factors, normalised to dose-area product (DAP), were estimated for chemoembolisation procedures using a Monte Carlo transport code in conjunction with an adult mathematical phantom. Exposure data from 32 patients were used to determine the exposure projections for the simulations. Equivalent organ (HT) and effective (E) doses were estimated using individual DAP values. The organs receiving the highest amount of doses during these exams were lumbar spine, liver and kidneys. The mean effective dose conversion factor was 1.4 Sv Gy-1 m-2 Dose conversion factors can be useful for patient-specific radiation burden during chemoembolisation procedures.


Subject(s)
Chemoembolization, Therapeutic , Liver Neoplasms/therapy , Monte Carlo Method , Phantoms, Imaging , Radiotherapy Planning, Computer-Assisted/methods , Adult , Humans , Prognosis , Radiotherapy Dosage
15.
Mol Endocrinol ; 29(10): 1454-67, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26280733

ABSTRACT

Progesterone (P4) maintains uterine quiescence during pregnancy and its functional withdrawal is associated with increased prostaglandin synthesis and the onset of labor. In primary human myometrial cells, the glucocorticoid receptor (GR) rather than the P4 receptor mediates P4 antagonism of IL-1ß-induced cyclooxygenase-2 (COX-2) expression, the rate-limiting enzyme in prostaglandin synthesis. We now report that P4 also acts via GR to induce MAPK phosphatase (MKP)-1 and knockdown of MKP-1 impairs the ability of P4 to repress IL-1ß-dependent COX-2 induction. Microarray analysis revealed that P4 repressed preferentially activator protein-1-responsive genes in response to IL-1ß. Consistent with these observations, we found that the ability of P4 to reduce c-Jun activation was lost upon GR as well as MKP-1 knockdown. Interestingly, c-Jun levels in human myometrial cells declined upon GR and MKP-1 knockdown, which suggests the presence of an activator protein-1 feedback loop. This is supported by our observation that c-Jun levels declined after an initial rise in primary myometrial cells treated with phorbol 12-myrisatate 13-acetate, a potent activator of c-Jun N-terminal kinase. Finally, we show that MKP-1 is an intermediate in P4-mediated repression of some but not all IL-1ß-responsive genes. For example, P4 repression of IL11 and IRAK3 was maintained upon MKP-1 knockdown. Taken together, the data show that P4 acts via GR to drive MKP-1 expression, which in turn inhibits IL-1ß-dependent c-Jun activation and COX-2 expression.


Subject(s)
Dual Specificity Phosphatase 1/metabolism , Inflammation/pathology , Myometrium/pathology , Progesterone/pharmacology , Transcription Factor AP-1/metabolism , Cyclooxygenase 2/metabolism , Feedback, Physiological/drug effects , Female , Gene Knockdown Techniques , Humans , Interleukin-1beta/pharmacology , Models, Biological , Myometrium/drug effects , Myometrium/metabolism , RNA, Small Interfering/metabolism , Receptors, Glucocorticoid/metabolism
16.
Science ; 349(6248): 638-43, 2015 Aug 07.
Article in English | MEDLINE | ID: mdl-26250684

ABSTRACT

Deltas are highly sensitive to increasing risks arising from local human activities, land subsidence, regional water management, global sea-level rise, and climate extremes. We quantified changing flood risk due to extreme events using an integrated set of global environmental, geophysical, and social indicators. Although risks are distributed across all levels of economic development, wealthy countries effectively limit their present-day threat by gross domestic product-enabled infrastructure and coastal defense investments. In an energy-constrained future, such protections will probably prove to be unsustainable, raising relative risks by four to eight times in the Mississippi and Rhine deltas and by one-and-a-half to four times in the Chao Phraya and Yangtze deltas. The current emphasis on short-term solutions for the world's deltas will greatly constrain options for designing sustainable solutions in the long term.


Subject(s)
Floods/economics , Floods/statistics & numerical data , Rivers , Forecasting , Humans , Investments , Risk
17.
Phys Med ; 31(7): 785-91, 2015 Nov.
Article in English | MEDLINE | ID: mdl-25900891

ABSTRACT

PURPOSE: To estimate the mean glandular dose of contrast enhanced digital mammography, using the EGSnrc Monte Carlo code and female adult voxel phantom. METHODS: Automatic exposure control of full field digital mammography system was used for the selection of the X-ray spectrum and the exposure settings for dual energy imaging. Measurements of the air-kerma and of the half value layers were performed and a Monte Carlo simulation of the digital mammography system was used to compute the mean glandular dose, for breast phantoms of various thicknesses, glandularities and for different X-ray spectra (low and high energy). RESULTS: For breast phantoms of 2.0-8.0 cm thick and 0.1-100% glandular fraction, CC view acquisition, from AEC settings, can result in a mean glandular dose of 0.450 ± 0.022 mGy -2.575 ± 0.033 mGy for low energy images and 0.061 ± 0.021 mGy - 0.232 ± 0.033 mGy for high energy images. In MLO view acquisition mean glandular dose values ranged between 0.488 ± 0.007 mGy - 2.080 ± 0.021 mGy for low energy images and 0.065 ± 0.012 mGy - 0.215 ± 0.010 mGy for high energy images. CONCLUSION: The low kV part of contrast enhanced digital mammography is the main contributor to total mean glandular breast dose. The results of this study can be used to provide an estimated mean glandular dose for individual cases.


Subject(s)
Contrast Media , Mammography/instrumentation , Monte Carlo Method , Phantoms, Imaging , Radiation Dosage , Radiographic Image Enhancement/instrumentation , Adult , Female , Humans , Radiometry
18.
Radiat Prot Dosimetry ; 165(1-4): 369-72, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25836682

ABSTRACT

Mammography is a standard procedure that facilitates breast cancer detection. Initial results of contrast-enhanced digital mammography (CEDM) are promising. The purpose of this study is to assess the CEDM radiation dose using a Monte Carlo code. EGSnrc MC code was used to simulate the interaction of photons with matter and estimate the glandular dose (Dg). A voxel female human phantom with a 2-8-cm breast thickness range and a breast glandular composition of 50 % was applied. Dg values ranged between 0.96 and 1.45 mGy (low and high energy). Dg values for a breast thickness of 5.0 cm and a glandular fraction of 50 % for craniocaudal and mediolateral oblique view were 1.12 (low energy image contribution is 0.98 mGy) and 1.07 (low energy image contribution is 0.95 mGy), respectively. The low kV part of CEDM is the main contributor to total glandular breast dose.


Subject(s)
Absorptiometry, Photon/methods , Contrast Media , Mammography/methods , Phantoms, Imaging , Radiographic Image Enhancement/methods , Adult , Air , Breast/pathology , Computer Simulation , Female , Humans , Monte Carlo Method , Neovascularization, Pathologic , Radiation Dosage , Radiometry
19.
Radiat Prot Dosimetry ; 163(2): 202-9, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24876338

ABSTRACT

Radiation protection and estimation of the radiological risk in paediatric radiology is essential due to children's significant radiosensitivity and their greater overall health risk. The purpose of this study was to estimate the organ and effective doses of paediatric patients undergoing barium meal (BM) examinations and also to evaluate the assessment of radiation Risk of Exposure Induced cancer Death (REID) to paediatric patients undergoing BM examinations. During the BM studies, fluoroscopy and multiple radiographs are involved. Since direct measurements of the dose in each organ are very difficult if possible at all, clinical measurements of dose-area products (DAPs) and the PCXMC 2.0 Monte Carlo code were involved. In clinical measurements, DAPs were assessed during examination of 51 patients undergoing BM examinations, separated almost equally in three age categories, neonatal, 1- and 5-y old. Organs receiving the highest amounts of radiation during BM examinations were as follows: the stomach (10.4, 10.2 and 11.1 mGy), the gall bladder (7.1, 5.8 and 5.2 mGy) and the spleen (7.5, 8.2 and 4.3 mGy). The three values in the brackets correspond to neonatal, 1- and 5-y-old patients, respectively. For all ages, the main contributors to the total organ and effective doses are the fluoroscopy projections. The average DAP values and absorbed doses to patient were higher for the left lateral projections. The REID was calculated for boys (4.8 × 10(-2), 3.0 × 10(-2) and 2.0 × 10(-2) %) for neonatal, 1- and 5-y old patients, respectively. The corresponding values for girl patients were calculated (12.1 × 10(-2), 5.5 × 10(-2) and 3.4 × 10(-2) %).


Subject(s)
Aging/physiology , Fluoroscopy , Models, Statistical , Radiation Dosage , Viscera/physiology , Whole-Body Counting/methods , Absorption, Radiation , Administration, Oral , Barium/administration & dosage , Child, Preschool , Computer Simulation , Contrast Media/administration & dosage , Humans , Infant , Infant, Newborn , Male , Monte Carlo Method , Organ Specificity/physiology , Software
20.
Epidemiol Infect ; 142(11): 2406-11, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24476750

ABSTRACT

This study reports the epidemiology of respiratory syncytial virus (RSV) in hospitalized children in Cyprus over three successive seasons (2010-2013) and the association between prevalent genotypes and disease severity. RSV infections had a circulation pattern from December to March. Most RSV-positive children (83%) were aged <2 years. Genotyping of RSV isolates showed that during the first winter season of the study (2010-2011), the only RSV genotype circulating was GA2 (RSV-A), followed by genotype BA (RSV-B) in the next winter season with only few sporadic cases of GA2. During the last winter season of the study (2012-2013) the newly emerged RSV genotype ON1 (RSV-A) was virtually the only circulating genotype. Children infected with genotype ON1 suffered a significantly milder illness compared to infections with genotypes GA2 and BA with a higher percentage of BA-infected children requiring oxygen. Our findings are in contrast to the majority of published reports that suggest RSV-A causes more severe illness than RSV-B. Therefore, further investigation of the association between RSV genotypes and disease severity is required, as it might affect treatment strategies in the future.


Subject(s)
Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Virus Infections/genetics , Respiratory Syncytial Viruses/genetics , Seasons , Age Distribution , Child , Child, Preschool , Cold Temperature , Cyprus/epidemiology , Female , Genotype , Hospitalization/statistics & numerical data , Humans , Male , Molecular Epidemiology , Polymerase Chain Reaction/methods , Prevalence , Respiratory Syncytial Viruses/isolation & purification , Retrospective Studies , Risk Factors , Severity of Illness Index
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