scholarly journals Link between personality and response to THC exposure

2019 ◽  
Author(s):  
Tetiana Kardash ◽  
Dmitry Rodin ◽  
Michael Kirby ◽  
Noa Davis ◽  
Igor Koman ◽  
...  
Keyword(s):  
Forced Swim Test ◽  
Behavioral Pattern ◽  
Place Preference ◽  
High Dose ◽  
Repeated Treatment ◽  
Corticosterone Concentration ◽  
Stress Vulnerability ◽  
Increased Risk ◽  
Conditioned Place Preference Paradigm ◽  
Different Doses

ABSTRACTThe effects of cannabis reported by users range from experiences of euphoria and anxiolytic effects to paranoia, anxiety, and increased risk of depression. Attempts to reconcile the apparent contradictions in user response have not been conclusive. Here, we utilized selectively-bred stress-resilient socially dominant (Dom) and stress-sensitive socially submissive (Sub) mice to elucidate this contradiction. Following short-term, repeated treatment with delta-9-tetrahydrocannabinol (THC) at two different doses (1.5 mg/kg and 15 mg/kg), Sub mice presented significant place-aversion in a Conditioned Place Preference paradigm at a high dose, whereas Dom mice displayed no place preference or aversion. Forced Swim test conducted after 6-week of washout period, revealed differential impact of the two THC doses depending upon behavioral pattern. Specifically, the low dose alleviated depressive-like behavior in Sub mice, while the high dose produced the opposite effect in Dom mice. Interestingly, corticosterone concentration in serum was elevated at the high dose regardless of the mice-population tested. We conclude here that differences in dominance behavior and stress vulnerability are involved in the regulation of cannabis response among users and should be considered when prescribing THC-containing medications to patients.

scholarly journals Albizia chinensis bark extract ameliorates the genotoxic effect of cyclophosphamide

2020 ◽  
Vol 44 (1) ◽  
Author(s):  
Marian Nabil ◽  
Entesar E. Hassan ◽  
Neven S. Ghaly ◽  
Fawzia A. Aly ◽  
Farouk R. Melek ◽  
...  
Keyword(s):  
Folk Medicine ◽  
Inhibitory Effect ◽  
Protective Role ◽  
Bark Extract ◽  
Repeated Treatment ◽  
Mouse Bone Marrow ◽  
Sperm Abnormalities ◽  
Wide Range ◽  
Different Doses

Abstract Background The genus Albizia (Leguminoseae) is used in folk medicine for the treatment of a wide range of ailments. Recently, saponins from plant origin have attracted much attention. Saponins are recorded to have a broad range of biological and pharmacological activities. This study was performed to evaluate the protective role of Albizia chinensis bark methanolic extract (MEAC) against the genotoxicity induced by cyclophosphamide (CP) using different mutagenic parameters. Results The results showed that MEAC induced an inhibitory effect against chromosomal aberrations of CP in mouse bone marrow and spermatocytes. Such effect was found to be significant (p < 0.01) with a dose of 100 mg/kg treated once for 24 h and also after repeated treatment at a dose of 25 mg/kg for 7 days. In sperm abnormalities, the protective effect of Albizia extract showed a dose-related relationship. Different doses of MEAC (25, 50, and 100 mg/kg) significantly (p < 0.01) ameliorated sperm abnormalities induced by CP dose-dependently. The percentage of sperm abnormalities was decreased to 5.14 ± 0.72 in the group of animals treated with CP plus MEAC (100 mg/kg) indicating an inhibitory effect of about 50%. Conclusion MEAC at the doses examined was non-genotoxic compared to control (negative) and exhibited a protective role against CP genotoxicity.

scholarly journals Adjuvant brachytherapy for FIGO stage I serous or clear cell endometrial cancer

2021 ◽  
pp. ijgc-2020-002217
Author(s):  
Elizabeth B Jeans ◽  
William G Breen ◽  
Trey C Mullikin ◽  
Brittany A Looker ◽  
Andrea Mariani ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Clear Cell ◽  
Early Stage ◽  
Figo Stage ◽  
Stage I ◽  
High Dose ◽  
Vaginal Cuff ◽  
Locoregional Failure ◽  
Platinum Based Chemotherapy ◽  
Increased Risk

ObjectivesOptimal adjuvant treatment for early-stage clear cell and serous endometrial cancer remains unclear. We report outcomes for women with surgically staged International Federation of Gynecology and Obstetrics (FIGO) stage I clear cell, serous, and mixed endometrial cancers following adjuvant vaginal cuff brachytherapy with or without chemotherapy.MethodsFrom April 1998 to January 2020, women with FIGO stage IA–IB clear cell, serous, and mixed endometrial cancer underwent surgery and adjuvant vaginal cuff brachytherapy. Seventy-six patients received chemotherapy. High-dose rate vaginal cuff brachytherapy was planned to a total dose of 21 gray in three fractions using a multichannel vaginal cylinder. The primary objective was to determine the effectiveness of adjuvant vaginal cuff brachytherapy and to identify surgicopathological risk factors that could portend towards worse oncological outcomes.ResultsA total of 182 patients were included in the analysis. Median follow-up was 5.3 years (2.3–12.2). Ten-year survival was 73.3%. Five-year cumulative incidence (CI) of vaginal, pelvic, and para-aortic relapse was 1.4%, 2.1%, and 0.9%, respectively. Five-year locoregional failure, any recurrence, peritoneal relapse, and other distant recurrence was 4.4%, 11.6%, 5.3%, and 6.7%, respectively. On univariate analysis, locoregional failure was worse for larger tumors (per 1 cm) (HR 1.9, 95% CI 1.2 to 3.0, p≤0.01). Any recurrence was worse for tumors of at least 3.5 cm (HR 3.8, 95% CI 1.3 to 11.7, p=0.02) and patients with positive/suspicious cytology (HR 4.4, 95% CI 1.5 to 12.4, p≤0.01). Ten-year survival for tumors of at least 3.5 cm was 56.9% versus 86.6% for those with smaller tumors (HR 2.9, 95% CI 1.4 to 5.8, p≤0.01). Ten-year survival for positive/suspicious cytology was 50.9% versus 77.4% (HR 2.2, 95% CI 0.9 to 5.4, p=0.09). Multivariate modeling demonstrated worse locoregional failure, any recurrence, and survival with larger tumors, as well as any recurrence with positive/suspicious cytology. Subgroup analysis demonstrated improved outcomes with the use of adjuvant chemotherapy in patients with large tumors or positive/suspicious cytology.ConclusionAdjuvant vaginal cuff brachytherapy alone without chemotherapy is an appropriate treatment for women with negative peritoneal cytology and small, early-stage clear cell, serous, and mixed endometrial cancer. Larger tumors or positive/suspicious cytology are at increased risk for relapse and worse survival, and should be considered for additional upfront adjuvant treatments, such as platinum-based chemotherapy.

scholarly journals Impact of Mantle Cell Lymphoma Contamination of Autologous Stem Cell Grafts on Outcome After High-Dose Chemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2558
Author(s):  
Malte Roerden ◽  
Stefan Wirths ◽  
Martin Sökler ◽  
Wolfgang A. Bethge ◽  
Wichard Vogel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mantle Cell Lymphoma ◽  
Clinical Decision Making ◽  
Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Mantle Cell ◽  
Autologous Grafts

Novel predictive factors are needed to identify mantle cell lymphoma (MCL) patients at increased risk for relapse after high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HDCT/Auto-HSCT). Although bone marrow and peripheral blood involvement is commonly observed in MCL and lymphoma cell contamination of autologous stem cell grafts might facilitate relapse after Auto-HSCT, prevalence and prognostic significance of residual MCL cells in autologous grafts are unknown. We therefore performed a multiparameter flow cytometry (MFC)-based measurable residual disease (MRD) assessment in autologous stem cell grafts and analyzed its association with clinical outcome in an unselected retrospective cohort of 36 MCL patients. MRD was detectable in four (11%) autologous grafts, with MRD levels ranging from 0.002% to 0.2%. Positive graft-MRD was associated with a significantly shorter progression-free and overall survival when compared to graft-MRD negative patients (median 9 vs. 56 months and 25 vs. 132 months, respectively) and predicted early relapse after Auto-HSCT (median time to relapse 9 vs. 44 months). As a predictor of outcome after HDCT/Auto-HSCT, MFC-based assessment of graft-MRD might improve risk stratification and support clinical decision making for risk-oriented treatment strategies in MCL.

scholarly journals ATRT-04. INHERITED RHABDOID PREDISPOSITION SYNDROME: A CASE OF CHOROID PLEXUS CARCINOMA AND ATYPICAL TERATOID RHABDOID TUMOR IN SIBLINGS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii276-iii276
Author(s):  
Alexis Judd ◽  
Erin Wright ◽  
Sarah Rush
Keyword(s):  
Overall Survival ◽  
Choroid Plexus ◽  
Disease Recurrence ◽  
Genetic Alterations ◽  
Rhabdoid Tumor ◽  
Choroid Plexus Carcinoma ◽  
High Dose ◽  
Atypical Teratoid Rhabdoid Tumor ◽  
Increased Risk ◽  
Atypical Teratoid

Abstract Choroid plexus carcinoma (CPC) and Atypical teratoid/rhabdoid tumor (ATRT) are aggressive, malignant brain cancers most commonly arising in children less than 3 years of age. These tumors often have genetic alterations in the tumor suppressor gene SMARCB1/INI1. Rhabdoid predisposition syndrome (RTPS) categorizes patients with germline mutations in SMARCB1 or SMARCA4, leading to a markedly increased risk of developing rhabdoid tumors. Both CPC and ATRT have been demonstrated in patients with these rhabdoid predisposition syndromes. In general, these tumors tend to have a poor prognosis. However, with the presence of a SMARCB1 mutation they may have improved overall survival. We present two interesting cases of siblings with maternally inherited SMARCB1 mutations: one a 21-month-old male who presented with an ATRT and another a 10 month old female who presented with a CPC. The ATRT was treated as per the Children’s Oncology Group study ACNS0333 with high dose chemotherapy and stem cell rescue as well as cranial radiation. The CPC was treated as per CPT-SIOP 2009 with etoposide, cyclophosphamide and vincristine. Unlike other patients with these aggressive tumors, both of these patients are alive without evidence of disease recurrence 8 and 7 years post therapy, respectively. Additional genomic testing on both tumors is currently pending in order to potentially identify other mutations that may impact survival. These cases further illustrate the similar profile of two very different tumors with improved overall survival that may be secondary to mutations in SMARCB1 in RTPS.

scholarly journals The interaction between 5-HTTLPR genotype and ruminative thinking on BMI

2017 ◽  
Vol 118 (8) ◽  
pp. 629-637 ◽  
Author(s):  
Robbie Schepers ◽  
C. Robert Markus
Keyword(s):  
Weight Gain ◽  
Cognitive Vulnerability ◽  
Young Male ◽  
Brain Serotonin ◽  
Hierarchical Regression ◽  
Allele Polymorphism ◽  
Stress Vulnerability ◽  
Increased Risk ◽  
Increase Energy Intake ◽  
S Allele

AbstractNegative affect or stress is often found to increase energy intake for high palatable energy-rich foods and hence weight gain. Reduced brain serotonin (5-HT) function is known to increase stress vulnerability and the risk for eating-related disturbances. A short (S) allele polymorphism in the serotonin transporter gene (5-HTTLPR) is associated with a less efficient functioning brain serotonin system and therefore higher stress vulnerability. It has been suggested that this genotype may be directly linked to an increased risk for weight gain and/or obesity. However, a high amount of variability has been apparent in replicating such a direct gene on weight gain relationship. A most recent suggestion is that this gene by weight relationship might be moderated by an additional (cognitive) vulnerability factor involving repetitive negative thinking (rumination). Our objective was to investigate whether the S-allele of 5-HTTLPR contributes to weight gain particularly in high cognitive ruminating individuals. A total of 827 healthy young male and female college students (aged 21·3 (sd 3·0) years; BMI 16–41·7 kg/m2) were genotyped for the 5-HTTLPR polymorphism and assessed for rumination (Event Related Ruminative Index) and body weight. In line with the hypothesis, a hierarchical regression model showed that higher BMI scores were observed in specifically high ruminating S'-carriers (P=0·031, f²=0·022). These results suggest that cognitive rumination may be a critical moderator of the association between 5-HTTLPR and body mass.

Mania with Bupropion: A Dose-Related Phenomenon?

2000 ◽  
Vol 34 (5) ◽  
pp. 619-621 ◽  
Author(s):  
Jessica L Goren ◽  
Gary M Levin
Keyword(s):  
Affective Disorder ◽  
Bipolar Depression ◽  
Bipolar Affective Disorder ◽  
Antidepressant Drug ◽  
Manic Episode ◽  
Total Daily Dose ◽  
High Dose ◽  
Related Phenomenon ◽  
Increased Risk ◽  
Daily Dose

OBJECTIVE: To report a case in which bipolar depression was resistant to usual therapies, requiring dosages of bupropion >450 mg/d and to review the literature on mania associated with bupropion and propose a potential theory of a dose-related threshold associated with bupropion and mania. CASE SUMMARY: A 44-year-old white man with a 25-year history of bipolar affective disorder presented with depression resistant to usual therapies. Bupropion therapy was initiated and the dosage was titrated to 600 mg/d. After exceeding the maximum recommended daily dose (450 mg/d), he experienced a manic episode attrib uted to high-dose bupropion. DISCUSSION: Due to increased risk of seizures, current prescribing guidelines state that the total daily dose of bupropion is not to exceed 450 mg/d. Since bupropion is the agent least likely to cause a manic switch in bipolar disorder, this agent seemed a logical choice to treat the patient's depression. Due to a lack of response, the bupropion dosage was titrated to a maximum of 600 mg/d. Since the patient did not switch into mania until the dosage exceeded 450 mg/d, we speculate that this adverse reaction is a dose-related phenomenon. Scientific literature supports this theory. CONCLUSIONS: A switch into mania is a potential risk associated with antidepressant drug use in bipolar affective disorder. Bupropion is believed to be associated with a decreased risk compared with other antidepressant therapies. However, our case report as well as others support the theory that this decreased risk may be due to dosages not exceeding the recommended daily dose (450 mg/d). Doses of bupropion >450 mg/d should be used with caution in depressed patients with bipolar affective disorder.

Influence of tranexamic acid use on venous thromboembolism risk in patients undergoing surgery for spine tumors

2021 ◽  
pp. 1-11
Author(s):  
Zach Pennington ◽  
Jeff Ehresman ◽  
Andrew Schilling ◽  
James Feghali ◽  
Andrew M. Hersh ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Tranexamic Acid ◽  
Vertebral Column ◽  
Comprehensive Cancer Center ◽  
Primary Study ◽  
High Dose ◽  
Data Set ◽  
Web Based ◽  
Spine Tumors ◽  
Increased Risk

OBJECTIVE Patients with spine tumors are at increased risk for both hemorrhage and venous thromboembolism (VTE). Tranexamic acid (TXA) has been advanced as a potential intervention to reduce intraoperative blood loss in this surgical population, but many fear it is associated with increased VTE risk due to the hypercoagulability noted in malignancy. In this study, the authors aimed to 1) develop a clinical calculator for postoperative VTE risk in the population with spine tumors, and 2) investigate the association of intraoperative TXA use and postoperative VTE. METHODS A retrospective data set from a comprehensive cancer center was reviewed for adult patients treated for vertebral column tumors. Data were collected on surgery performed, patient demographics and medical comorbidities, VTE prophylaxis measures, and TXA use. TXA use was classified as high-dose (≥ 20 mg/kg) or low-dose (< 20 mg/kg). The primary study outcome was VTE occurrence prior to discharge. Secondary outcomes were deep venous thrombosis (DVT) or pulmonary embolism (PE). Multivariable logistic regression was used to identify independent risk factors for VTE and the resultant model was deployed as a web-based calculator. RESULTS Three hundred fifty patients were included. The mean patient age was 57 years, 53% of patients were male, and 67% of surgeries were performed for spinal metastases. TXA use was not associated with increased VTE (14.3% vs 10.1%, p = 0.37). After multivariable analysis, VTE was independently predicted by lower serum albumin (odds ratio [OR] 0.42 per g/dl, 95% confidence interval [CI] 0.23–0.79, p = 0.007), larger mean corpuscular volume (OR 0.91 per fl, 95% CI 0.84–0.99, p = 0.035), and history of prior VTE (OR 2.60, 95% CI 1.53–4.40, p < 0.001). Longer surgery duration approached significance and was included in the final model. Although TXA was not independently associated with the primary outcome of VTE, high-dose TXA use was associated with increased odds of both DVT and PE. The VTE model showed a fair fit of the data with an area under the curve of 0.77. CONCLUSIONS In the present cohort of patients treated for vertebral column tumors, TXA was not associated with increased VTE risk, although high-dose TXA (≥ 20 mg/kg) was associated with increased odds of DVT or PE. Additionally, the web-based clinical calculator of VTE risk presented here may prove useful in counseling patients preoperatively about their individualized VTE risk.

Effect of Different Doses of Propofol and Nerve block Combined with General Anesthesia on The Intraoperative Anesthesia and Postoperative Awakening and Cognitive Function in Elderly Patients with Knee Osteoarthritis

2021 ◽  
Vol 7 (4) ◽  
pp. 697-705
Author(s):  
Jianhui Ma ◽  
Meimei Pang ◽  
Xin Ding ◽  
Shirong Fang ◽  
Lichao Chu
Keyword(s):  
Cognitive Function ◽  
Elderly Patients ◽  
General Anesthesia ◽  
Nerve Block ◽  
Dose Group ◽  
Low Dose ◽  
High Dose Group ◽  
High Dose ◽  
Knee Oa ◽  
Different Doses

Objective. To explore the effect of different doses of propofol and nerve block combined with general anesthesia on the intraoperative anesthesia and postoperative awakening and cognitive function in elder patients with knee osteoarthritis (OA). Methods. According to the inclusion criteria for research object, we selected 98 elderly patients with knee OA who needed surgery and were admitted to our hospital from January 2019 to January 2021 for the study. Patients were divided into the low dose group (given 2 mg/kg propofol by pumping under constant speed during surgery) and the high dose group (given 4 mg/kg propofol by pumping during surgery) by the number table method to compare their indicators including the intraoperative anesthesia effect, with 49 cases in each group. Results. No between-group difference was shown in the anesthesia time and postoperative VAS scores, but the awakening time of the low dose group was significantly shorter than that of the high dose group (P<0.05); the differences in heart rate (HR) values at various time points between the two groups were not obvious, but the high dose group obtained significantly higher HR values at T4 than the low dose group; the mean arterial pressure (MAP) values of both groups were significantly reduced at Ti and then returned to the level before anesthesia (P>0.05); the bispectral index scores (BIS) of both groups experienced a marked drop at Ti and then recovered gradually, but failed to return to the level at T0 till the end, and a between-group difference in BIS indexes presented at Ti; the plasma corticosterone (CORT) concentration at Ti of both groups were significantly lowered and then returned to the level at T0, with no between-group difference; and compared with the low dose group, the high dose group achieved slightly lower mini-mental state examination (MMSE) scores at 24-72 h after surgery, with no significant difference between them (P>0.05). Conclusion. The therapy of different doses of propofol and nerve block combined with general anesthesia has no significant effect on the cognitive function in elderly knee OA patients after surgery. With the nerve block improving the analgesic effect, a low dose of propofol is good for the postoperative awakening of patients. Different doses of propofol inhibited the stress response to a different degree and produced good anesthesia outcomes in elderly patients, but comparatively speaking, a low-dose propofol ensures more smooth indexes and less effect on the intraoperative hemodynamics.

A major health problem facing immigrant children: nutritional rickets

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Erdal Kurnaz ◽  
Semra Çetinkaya ◽  
Selin Elmaoğulları ◽  
Aslıhan Araslı Yılmaz ◽  
Nursel Muratoğlu Şahin ◽  
...  
Keyword(s):  
Vitamin D ◽  
Immigrant Children ◽  
High Dose ◽  
Pediatric Endocrinology ◽  
Major Health Problem ◽  
Nutritional Rickets ◽  
Increased Risk ◽  
Long Term Follow Up

Abstract Objectives Nutritional rickets (NR) is still an important problem and one which increasing influxes of immigrants are further exacerbating. This study evaluated cases of mostly immigrant children followed up with diagnoses of NR in our pediatric endocrinology clinic. Methods Details of 20 cases diagnosed with NR between 2017 and 2020 were retrieved from file records. Results Twenty (11 male) cases were included in the study. Three (15%) were Turkish nationals and the others (85%) were immigrants. Hypocalcemia and hypophosphatemia were detected in 17 and 13, respectively. Alkaline phosphatase (ALP) values were normal in two cases, while ALP and parathyroid hormone (PTH) values were elevated in all other cases, and PTH levels were very high (473.64 ± 197.05 pg/mL). 25-hydroxyvitamin D levels were below 20 ng/mL in all cases. Patients with NR received high-dose long-term vitamin D or stoss therapy. Six patients failed to attend long-term follow-up, while PTH and ALP levels and clinical findings improved at long-term follow-up in the other 14 cases. Conclusions The elevated PTH levels suggest only the most severe cases of NR presented to our clinic. Clinically evident NR is therefore only the tip of the iceberg, and the true burden of subclinical rickets and osteomalacia remains unidentified. Public health policies should therefore focus on universal vitamin D supplementation and adequate dietary calcium provision, their integration into child surveillance programs, adequate advice and support to ensure normal nutrition, exposure to sunlight, and informing families of the increased risk not only for resident populations but also for refugee and immigrant children.

Sign in / Sign up

Export Citation Format

Share Document