• Title/Summary/Keyword: Organs at risk

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Dexamethasone, but Not Vitamin D or A, Dampens the Inflammatory Neutrophil Response to Protect At-risk COVID-19 Patients

  • Florianne M.J. Hafkamp;Sanne Mol;Iris Waque;Esther C. De Jong
    • IMMUNE NETWORK
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    • v.22 no.4
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    • pp.36.1-36.12
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    • 2022
  • Dexamethasone (DEX) was the first drug shown to save lives of critically ill coronavirus disease 2019 (COVID-19) patients suffering from respiratory distress. A hyperactivated state of neutrophils was found in COVID-19 patients compared to non-COVID pneumonia cases. Given the beneficial effects of DEX in COVID-19 patients, we investigated the effects of DEX and of other immunomodulatory drugs vitamin D3 (VD3) and retinoic acid (RA) on neutrophil function. DEX, but not VD3 or RA, significantly inhibited all tested aspects of neutrophil function, e.g., degranulation, intracellular ROS production, CXCL8 release and NETosis. Interestingly, RA displayed the opposite effect by significantly increasing both CXCL8 and NET release by neutrophils. Taken together, these data suggest that the lower COVID-19 mortality in DEX-treated patients may in part be due to the dampening effect of DEX on the inflammatory neutrophil response, which could prevent neutrophil plugs with NETS in the lungs and other inflamed organs of patients.

Permitted Daily Exposure for Diisopropyl Ether as a Residual Solvent in Pharmaceuticals

  • Romanelli, Luca;Evandri, Maria Grazia
    • Toxicological Research
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    • v.34 no.2
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    • pp.111-125
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    • 2018
  • Solvents can be used in the manufacture of medicinal products provided their residual levels in the final product comply with the acceptable limits based on safety data. At worldwide level, these limits are set by the "Guideline Q3C (R6) on impurities: guideline for residual solvents" issued by the ICH. Diisopropyl ether (DIPE) is a widely used solvent but the possibility of using it in the pharmaceutical manufacture is uncertain because the ICH Q3C guideline includes it in the group of solvents for which "no adequate toxicological data on which to base a Permitted Daily Exposure (PDE) was found". We performed a risk assessment of DIPE based on available toxicological data, after carefully assessing their reliability using the Klimisch score approach. We found sufficiently reliable studies investigating subchronic, developmental, neurological toxicity and carcinogenicity in rats and genotoxicity in vitro. Recent studies also investigated a wide array of toxic effects of gasoline/DIPE mixtures as compared to gasoline alone, thus allowing identifying the effects of DIPE itself. These data allowed a comprehensive toxicological evaluation of DIPE. The main target organs of DIPE toxicity were liver and kidney. DIPE was not teratogen and had no genotoxic effects, either in vitro or in vivo. However, it appeared to increase the number of malignant tumors in rats. Therefore, DIPE could be considered as a non-genotoxic animal carcinogen and a PDE of 0.98 mg/day was calculated based on the lowest No Observed Effect Level (NOEL) value of $356mg/m^3$ (corresponding to 49 mg/kg/day) for maternal toxicity in developmental rat toxicity study. In a worst-case scenario, using an exceedingly high daily dose of 10 g/day, allowed DIPE concentration in pharmaceutical substances would be 98 ppm, which is in the range of concentration limits for ICH Q3C guideline class 2 solvents. This result might be considered for regulatory decisions.

The Role of Bloodletting and Cupping in Severe Acute Urticaria and Angioedema as Skin Emergencies in Persian Medicine

  • Shirazi, Maryam Taghavi;Kenari, Hoorieh Mohammadi;Eghbalian, Fatemeh
    • Journal of Pharmacopuncture
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    • v.25 no.1
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    • pp.7-14
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    • 2022
  • Objectives: Some dermatological diseases can be life-threatening. Urticaria and angioedema are common reasons for patients to seek treatment at an emergency department. Severe, generalized urticaria and angioedema can endanger patients' lives by involving the airways and causing anaphylactic shock. The humor-based Persian Medicine (PM) concepts of Shara and Mashara, referring to two kinds of skin lesions, have similarities to urticaria and angioedema, respectively. This article aims to provide scientific evidence regarding the application of PM as an early intervention strategy in the emergency management of urticaria and angioedema. Methods: This was a narrative review of PM studies identified by searching medical databases using search terms related to these diseases, as well as risk-associated keywords such as "fatal", "death", "life-threatening", "emergency", "cupping", and "bloodletting". Data were then compared, interpreted, and analyzed. Results: PM scholars consider the human body as a unified whole and believe in an inner power (Nature) which stems from the body. When the presence of excessive hot substances cause an imbalance of bodily humors, Nature directs their heated vapors sharply toward the skin, thus causing Shara and Mashara. If there is a high risk of inflammation spreading to vital organs under severe conditions, urgent manual interventions are crucial. Conclusion: In serious conditions of urticaria and angioedema, Fasd or bloodletting and Hijama can be effective in speeding up the control of lesions and reducing morbidity and mortality. Consequently, the development of integrated Persian and conventional medicines may provide new therapeutic pathways for skin emergencies.

Evaluation of Treatment Plan Quality between Magnetic Resonance-Guided Radiotherapy and Volumetric Modulated Arc Therapy for Prostate Cancer

  • Chang Heon Choi;Jin Ho Kim;Jaeman Son;Jong Min Park;Jung-in Kim
    • Progress in Medical Physics
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    • v.33 no.4
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    • pp.121-128
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    • 2022
  • Purpose: This study evaluated the quality of plans based on magnetic resonance-guided radiotherapy (MRgRT) tri-Co-60, linac, and conventional linac-based volumetric modulated arc therapy (linac-VMAT) for prostate cancer. Methods: Twenty patients suffering from prostate cancer with intermediate risk who were treated by MAT were selected. Additional treatment plans (primary and boost plans) were generated based on MRgRT-tri-Co-60 and MRgRT-linac. The planning target volume (PTV) of MRgRT-based plans was created by adding a 3 mm margin from the clinical target volume (CTV) due to high soft-tissue contrast and real-time motion imaging. On the other hand, the PTV of conventional linac was generated based on a 1 cm margin from CTV. The targets of primary and boost plans were prostate plus seminal vesicle and prostate only, respectively. All plans were normalized to cover 95% of the target volume by 100% of the prescribed dose. Dosimetric characteristics were evaluated for each of the primary, boost, and sum plans. Results: For target coverage and conformity, the three plans showed similar results. In the sum plans, the average value of V65Gy of the rectum of MRgRT-linac (2.62%±2.21%) was smaller than those of MRgRT tri-Co-60 (9.04%±3.01%) and linac-VMAT (9.73%±7.14%) (P<0.001). In the case of bladder, the average value of V65Gy of MRgRT-linac was also smaller. Conclusions: In terms of organs at risk sparing, MRgRT-linac shows the best value while maintaining comparable target coverage among the three plans.

Comparison of 2D and 3D Brachytherapy Planning for Cervical Cancer (자궁경부암 근접방사선치료 시 2차원, 3차원 치료계획 비교평가)

  • Kim, Jung Hoon
    • Journal of radiological science and technology
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    • v.40 no.2
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    • pp.303-309
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    • 2017
  • To evaluate the usefulness of 3-dimensional brachytherapy(BT) planning technique based on CT in cervical cancer. Patients with cervical cancer underwent 2-D BT treatment planning and then CT scan with HDR intracavitary applicators in place with same positions. Dose was prescribed to Point A with 5Gy per fraction on 2-D BT planning. For 3-D BT planning, and dose was prescribed to the High risk CTV for BT (HR CTV) with 5Gy. The 3-D BT planning goal was to cover at least 90% of the HR CTV with target 5Gy isodose surface while limiting the dose to $2cm^3$ of bladder to less than 7.5 Gy, and $2cm^3$ of rectum to less than 5Gy. In one patient of 10 patients, $D_{2cm3}$ of rectal dose was over 5Gy and 6patients at $D_{2cm3}$ of bladder dose on 2-D BT planning. There was a tendency to underestimate ICRU bladder dose than ICRU rectal dose. CT based 3-D BT planning for cervical cancer will enable evaluation of dose distributions for tumor and critical organs at risk. So, rectal and bladder morbidity as well as geographic miss will be reduced in case of the bulky disease or uterine malposition.

Evaluation of Beam-Matching Accuracy for 8 MV Photon Beam between the Same Model Linear Accelerator (동일 기종 선형가속기간 8 MV 광자선에 대한 빔 매칭 정확도 평가)

  • Kim, Yon-Lae;Chung, Jin-Beom;Kang, Seong-Hee
    • Journal of radiological science and technology
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    • v.43 no.2
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    • pp.105-114
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    • 2020
  • This study aimed to assess of beam-matching accuracy for an 8 MV beam between the same model linear accelerators(Linac) commissioned over two years. Two models were got the customer acceptance procedure(CAP) criteria. For commissioning data for beam-matched linacs, the percentage depth doses(PDDs), beam profiles, output factors, multi-leaf collimator(MLC) leaf transmission factors, and the dosimetric leaf gap(DLG) were compared. In addition, the accuracy of beam matching was verified at phantom and patient levels. At phantom level, the point doses specified in TG-53 and TG-119 were compared to evaluate the accuracy of beam modelling. At patient level, the dose volume histogram(DVH) parameters and the delivery accuracy are evaluated on volumetric modulated arc therapy(VMAT) plan for 40 patients that included 20 lung and 20 brain cases. Ionization depth curve and dose profiles obtained in CAP showed a good level for beam matching between both Linacs. The variations in commissioning beam data, such as PDDs, beam profiles, output factors, TF, and DLG were all less than 1%. For the treatment plans of brain tumor and lung cancer, the average and maximum differences in evaluated DVH parameters for the planning target volume(PTV) and the organs at risk(OARs) were within 0.30% and 1.30%. Furthermore, all gamma passing rates for both beam-matched Linacs were higher than 98% for the 2%/2 mm criteria and 99% for the 2%/3 mm criteria. The overall variations in the beam data, as well as tests at phantom and patient levels remains all within the tolerance (1% difference) of clinical acceptability between beam-matched Linacs. Thus, we found an excellent dosimetric agreement to 8 MV beam characteristics for the same model Linacs.

Correlation between the time elapsed after liposuction and the risk of fat embolism: An animal model

  • Lim, Kwang-Ryeol;Cho, Jeong-Min;Yoon, Chung-Min;Lee, Keun-Cheol;Lee, Sang-Yun;Ju, Mi-Ha
    • Archives of Plastic Surgery
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    • v.45 no.1
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    • pp.14-22
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    • 2018
  • Background Liposuction has become one of the most frequently performed procedures in the field of aesthetic surgery. Fat embolism syndrome after liposuction can easily be overlooked or underestimated; however, occasionally, fulminating fat embolism syndrome can develop and lead to a critical situation within 2-3 days after lipoplasty. Changes over time in the amount of circulating fat particles and the histology of major organs have not yet been studied. Methods This study was conducted using 18 male Sprague-Dawley rats aged 12 weeks and weighing 500-628 g (average, 562 g). Fifteen rats were used as the experimental group and 3 as the control group. Under general anesthesia, tumescent-technique liposuction was performed at the lateral flank areas and abdomen for 1 hour. Blood, lung, and brain tissue specimens were obtained at 1 hour, 1 day, and 2 days after the liposuction procedure. Results The average number of fat particles in the blood samples was 25,960/dL at 1 hour, 111,100/dL at 24 hours, and 21,780/dL at 48 hours. The differences between study groups were statistically significant. Both intravascular and extravascular fat particles with inflammation were seen in all 15 rats, as were inflammatory cell infiltration, hemorrhage, and consolidation with shrinkage of the lung alveoli. Conclusions These results imply that there is a strong possibility of fat embolism syndrome after liposuction in real clinical practice, and the first 24-48 hours after the operation were found to be the most important period for preventing pulmonary embolism and progression to fulminating fat embolism syndrome.

CT Based 3-Dimensional Treatment Planning of Intracavitary Brachytherapy for Cancer of the Cervix : Comparison between Dose-Volume Histograms and ICRU Point Doses to the Rectum and Bladder

  • Hashim, Natasha;Jamalludin, Zulaikha;Ung, Ngie Min;Ho, Gwo Fuang;Malik, Rozita Abdul;Ee Phua, Vincent Chee
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.13
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    • pp.5259-5264
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    • 2014
  • Background: CT based brachytherapy allows 3-dimensional (3D) assessment of organs at risk (OAR) doses with dose volume histograms (DVHs). The purpose of this study was to compare computed tomography (CT) based volumetric calculations and International Commission on Radiation Units and Measurements (ICRU) reference-point estimates of radiation doses to the bladder and rectum in patients with carcinoma of the cervix treated with high-dose-rate (HDR) intracavitary brachytherapy (ICBT). Materials and Methods: Between March 2011 and May 2012, 20 patients were treated with 55 fractions of brachytherapy using tandem and ovoids and underwent post-implant CT scans. The external beam radiotherapy (EBRT) dose was 48.6Gy in 27 fractions. HDR brachytherapy was delivered to a dose of 21 Gy in three fractions. The ICRU bladder and rectum point doses along with 4 additional rectal points were recorded. The maximum dose ($D_{Max}$) to rectum was the highest recorded dose at one of these five points. Using the HDRplus 2.6 brachyhtherapy treatment planning system, the bladder and rectum were retrospectively contoured on the 55 CT datasets. The DVHs for rectum and bladder were calculated and the minimum doses to the highest irradiated 2cc area of rectum and bladder were recorded ($D_{2cc}$) for all individual fractions. The mean $D_{2cc}$ of rectum was compared to the means of ICRU rectal point and rectal $D_{Max}$ using the Student's t-test. The mean $D_{2cc}$ of bladder was compared with the mean ICRU bladder point using the same statistical test. The total dose, combining EBRT and HDR brachytherapy, were biologically normalized to the conventional 2 Gy/fraction using the linear-quadratic model. (${\alpha}/{\beta}$ value of 10 Gy for target, 3 Gy for organs at risk). Results: The total prescribed dose was $77.5Gy{\alpha}/{\beta}10$. The mean dose to the rectum was $4.58{\pm}1.22Gy$ for $D_{2cc}$, $3.76{\pm}0.65Gy$ at $D_{ICRU}$ and $4.75{\pm}1.01Gy$ at $D_{Max}$. The mean rectal $D_{2cc}$ dose differed significantly from the mean dose calculated at the ICRU reference point (p<0.005); the mean difference was 0.82 Gy (0.48-1.19Gy). The mean EQD2 was $68.52{\pm}7.24Gy_{{\alpha}/{\beta}3}$ for $D_{2cc}$, $61.71{\pm}2.77Gy_{{\alpha}/{\beta}3}$ at $D_{ICRU}$ and $69.24{\pm}6.02Gy_{{\alpha}/{\beta}3}$ at $D_{Max}$. The mean ratio of $D_{2cc}$ rectum to $D_{ICRU}$ rectum was 1.25 and the mean ratio of $D_{2cc}$ rectum to $D_{Max}$ rectum was 0.98 for all individual fractions. The mean dose to the bladder was $6.00{\pm}1.90Gy$ for $D_{2cc}$ and $5.10{\pm}2.03Gy$ at $D_{ICRU}$. However, the mean $D_{2cc}$ dose did not differ significantly from the mean dose calculated at the ICRU reference point (p=0.307); the mean difference was 0.90 Gy (0.49-1.25Gy). The mean EQD2 was $81.85{\pm}13.03Gy_{{\alpha}/{\beta}3}$ for $D_{2cc}$ and $74.11{\pm}19.39Gy_{{\alpha}/{\beta}3}$ at $D_{ICRU}$. The mean ratio of $D_{2cc}$ bladder to $D_{ICRU}$ bladder was 1.24. In the majority of applications, the maximum dose point was not the ICRU point. On average, the rectum received 77% and bladder received 92% of the prescribed dose. Conclusions: OARs doses assessed by DVH criteria were higher than ICRU point doses. Our data suggest that the estimated dose to the ICRU bladder point may be a reasonable surrogate for the $D_{2cc}$ and rectal $D_{Max}$ for $D_{2cc}$. However, the dose to the ICRU rectal point does not appear to be a reasonable surrogate for the $D_{2cc}$.

Analysis of the Risk Factors Influencing the Severity of Injury in Pediatric Multiple Trauma Patients (소아 다발성 외상 환자의 중증도에 영향을 미치는 위험인자에 관한 분석)

  • Lee, Gang-Wook;Kim, Sun-Pyo;Kim, Seong-Jung;Cho, Soo-Hyung;Cho, Nam-Soo
    • Journal of Trauma and Injury
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    • v.23 no.2
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    • pp.68-74
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    • 2010
  • Purpose: The purpose of this study is, first, to analyze the risk factors that influence the severity of injury in pediatric multiple trauma patients and, second, to present solutions for the problems related to the treatment of such patients. Our living situations are so complicated that the danger of accidents is truly open to children who are not prepared. We need to draw attention to the increased numbers of various accidents involving children. Methods: We studied patients who visited the Emergency Medical Center at Chosun University Hospital from January 1, 2006, to December 31, 2008. Using medical records, we evaluated the general characteristics: the mechanism of injury, the vital signs, the revised trauma score (RTS), the injury severity score (ISS), and the hemoglibin value, which was checked at the time of visit, and the presence or the absence of emergent on regular surgery. We divided the level of injury as follows: light level (1-8 points), mid level (9-15 points), and serious level (above 16 points). We analyzed the medical data by using SPSS 17.0 for windows. Results: The average age of the patients examined was 8.6 years. The number of 6- to 11-year-old patients was 96, which was the largest, but the degree of injury severity was the highest among infant (0-2 years), according to ISS 7.95(${\pm}6.85$). The frequency of accidents was highest on sunny days, and most accidents occurred from 16:00 to 20:00. The cause of multiple trauma for children was the greatest in the traffic accident, (95 patients, 49.0%). In addition, the trauma caused by traffic accidents showed the highest ISS value ($9.02{\pm}6.42$) and the most serious degree (P=0.004). The ISS level of injury ($8.40{\pm}6.64$) for patients moved from a secondary hospital was higher than that ($6.49{\pm}5.57$) for patients who visited the medical center directly. The severity of injury was highest for patients who used a 119 ambulance ($8.84{\pm}5.80$). According to the injured parts of body, Injuries to the arms and the feet most frequent (79 patients, 40.7%), but the level of injury was the highest for internal organs and chest, $16.42{\pm}8.56$ and $11.23{\pm}6.97$, respectively. Conclusion: We used Abbreviated Injury Scale (AIS) in order to examine the characteristics by injured body part for pediatric multiple trauma patients. Because the degree of injury was the highest for internal organs or the chest, we need to more seriously examine and provide for patients who are suspected of having injuries to the internal organs or the chest. We need to quickly determine the need for surgery in patients with serious injuries to the arms and the feet, which is the greatest in frequency. In particular, we need to consider the surgical care of patients who are not very high in the severity of injury to their brains.

The Relationship between Food Habit, Nutrient Intakes and Bone Mineral Density and Bone Mineral Content in Adult Women (성인여성의 식습관과 영양섭취상태와 골밀도 및 골무기질함량과의 관계)

  • 최미자;정윤정
    • Journal of Nutrition and Health
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    • v.31 no.9
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    • pp.1446-1456
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    • 1998
  • Bones are important parts in sustaining the shape of the body, but they are also metabolic organs which undergo bone remodeling by constant bone resorption and formation. Osteoporosis, the typical metabolic bone disease, is characterized by a reduction in bone mineral density (BMD). Women more than men are at risk fir osteoporosis-related fractures, especially in the lumbar spine, wrist, and hip region. Risk of fracture depends on one's BMD, which open determined by the peak bone mass value achieved at skeletal maturity and followed by subsequent age-and menopause-related bone loss. Genetic and environmental factors are known to play a key role in bone metabolism and diet is considered as one of the important environmental factors. The purpose of the present study was to assess the status of BMD and bone mineral content(BMC) to clarify the relationships between dietary intakes and the risk of osteoporosis in adult women in Taegu. Subjects were 130 healthy females in between 20 and 69 years of age. BMD and BMC of the lumbar spine(venebrae L2-4) of the subjects were measured by dual energy X-ray absorptiometry. The average age of the subjects was 47.4${\pm}$11.7 years old, the average weight was 57.2${\pm}$8.4kg, the average age of menarche was 16.6${\pm}$1.9 years old and the average age of menopause was 48.4${\pm}$5.3 years old. The nutrient intakes of the subjects measured by the convenient method were generally lower than the level of RDA. The result of nutrient intake assessed has shown that the average energy intake was 1701${\pm}$316kca1 which is 85.1% of the RDA and the average calcium intake was 485.4${\pm}$172.3mg which is 69.3% of the RDA. The intakes of protein, vitamin A, vitamin B$_1$, niacin were greater than the RDA, whereas the remaining nutrient intakes were lower than the RDA. The average BMD of the subjects was shown to be 1.06${\pm}$1.09g/$\textrm{cm}^2$. The highest BMD of 1.24${\pm}$0.14g/$\textrm{cm}^2$ was noticed in the subjects of 30s compared to 20s, 40s, 50s, 60s. The BMD values were compared by the relative body weight(R3W) of the menopause subjects, and it was found that the underweight group had significant lower BMB while the rest of the groups did not have any differences in BMD. The most strongly correlated nutrient with BMD among the menopause subjects appeared to be calcium. The women whose Ca intakes were higher than 500mg showed the significantly higher BMD than those with Ca intakes lower than 500mg. This study suggests that the most effective way to prevent osteoporosis and to reduce the incidences of fractures seems to be minimizing bone loss through the adequate intake of calcium as well as avoiding underweight, especially in menopausal women. (Korean J Nutrition 31(9) . 1446-1456, 1998)

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