scholarly journals Induction of colorectal carcinogenesis in the C57BL/6J and A/J mouse strains with a reduced DSS dose in the AOM/DSS model

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Henriette Arnesen ◽  
Mette Helen Bjørge Müller ◽  
Mona Aleksandersen ◽  
Gunn Charlotte Østby ◽  
Harald Carlsen ◽  
...  
Keyword(s):  
Outcome Measures ◽  
Low Dose ◽  
Dextran Sulfate ◽  
Clinical Symptoms ◽  
Colorectal Carcinogenesis ◽  
Mouse Strains ◽  
Chemical Induction ◽  
Preneoplastic Lesions ◽  
Future Studies ◽  
Treatment Regimens

Abstract Background Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide and thus mouse models of CRC are of significant value to study the pathogenesis. The Azoxymethane/Dextran sulfate sodium (AOM/DSS) model is a widely used, robust initiation-promotion model for chemical induction of colitis-associated CRC in rodents. However, the dosage of chemicals, treatment regimens and outcome measures vary greatly among studies employing this model. Thus, the aim of this study was to examine an AOM/DSS model involving a reduced (1%) dose of DSS for induction of carcinogenesis in A/J and C57BL/6J (B6) mice. Results We show that colonic preneoplastic lesions can be reliably detected in A/J and B6 mice by use of a AOM/DSS model involving a single injection of 10 mg/kg AOM followed by three 7-day cycles of a low-dose (1%) DSS administration. Supporting existing evidence of A/J mice exhibiting higher susceptibility to AOM than B6 mice, our AOM/DSS-treated A/J mice developed the highest number of large colonic lesions. Clinical symptoms in both strains subjected to the AOM/DSS treatment did not persist in-between treatment cycles, demonstrating that the animals tolerated the treatment well. Conclusions Our findings suggest that a reduced dose of DSS in the AOM/DSS model can be considered in future studies of early phase colorectal carcinogenesis in the A/J and B6 mouse strains using preneoplastic lesions as an outcome measure, and that such regimen may reduce the risk of early trial terminations to accommodate human endpoints. Overall, our data emphasize the importance of devoting attention towards choice of protocol, outcome measures and mouse strain in studies of CRC in mice according to the study purpose.

Planning and approach to allergen-specific immunotherapy in polyallergic patients

Immunotherapy ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 577-585
Author(s):  
Nerin N Bahceciler ◽  
Ozel Yuruker
Keyword(s):  
Clinical Management ◽  
Respiratory Diseases ◽  
Specific Immunotherapy ◽  
Clinical Symptoms ◽  
Allergen Specific Immunotherapy ◽  
Stepwise Approach ◽  
Future Studies ◽  
Disease Modifying ◽  
Management Recommendations ◽  
Disease Modifying Treatment

Allergy immunotherapy (AIT) is currently the only disease-modifying treatment for allergic-respiratory diseases. Polysensitization may increase the severity of current disease resulting in subsequent asthma development in patients with allergic rhinitis. Due to the absence of general recommendations for the practical approach to polysensitized patients, clinical management is not standardized. The correlation between sensitizations and clinical symptoms, elimination of possible pollen cross-reactivities and principles of homologous allergen groups will guide the allergists to deduce the most relevant allergens for AIT. In the highlight of the previously proposed approach strategies to polyallergic patients, hereby we propose a revised practical stepwise approach based on the current European Medicine Agency (EMA) guidelines. However, more supporting data from well-designed, controlled, future studies are needed to improve clinical management recommendations for AIT in polyallergic patients.

scholarly journals Low Dose Ketamine Infusion for Comorbid Posttraumatic Stress Disorder and Chronic Pain: A Randomized Double-Blind Clinical Trial

2020 ◽  
Vol 4 ◽  
pp. 247054702098167
Author(s):  
Alisher R. Dadabayev ◽  
Sonalee A. Joshi ◽  
Mariam H. Reda ◽  
Tamar Lake ◽  
Mark S. Hausman ◽  
...  
Keyword(s):  
Posttraumatic Stress Disorder ◽  
Chronic Pain ◽  
Posttraumatic Stress ◽  
Outcome Measures ◽  
Low Dose ◽  
Stress Disorder ◽  
Double Blind ◽  
Impact Of Event Scale ◽  
Event Scale ◽  
Ketamine Infusion

Objective To date, treatment options (i.e. psychotherapy, antidepressant medications) for patients with posttraumatic stress disorder (PTSD), are relatively few, and considering their limited efficacy, novel therapies have gained interest among researchers and treatment providers alike. Among patients with chronic pain (CP) about one third experience comorbid PTSD, which further complicates their already challenging pharmacological regimens. Low dose ketamine infusion has shown promise in PTSD, and in treatment of CP, however they have not been studied in comorbid population and under rigorous control conditions. Methods We compared the effects of a single dose of either ketamine (0.5 mg/kg) or ketorolac (15 mg) over a 40-minute of IV infusion in CP patients with and without PTSD, in double blind, randomized study. Measures were collected before, during, one day and seven days after the infusion. A planned sample size of 40 patients randomly assigned to treatment order was estimated to provide 80% power to detect a hypothesized treatment difference after the infusion. Main Outcome and Measures: The primary outcome measures were change in PTSD symptom severity assessed with the Impact of Event Scale–Revised (IES-R) and Visual Analogue Scale (VAS) for pain administered by a study clinician 24 hours post infusion. Secondary outcome measures included Impact of Event Scale–Revised (IES-R), VAS and Brief Pain Inventory (Short Form) for pain 1 week after the infusion. Results Both treatments offered comparable improvement of PTSD and CP symptoms that persisted for 7 days after the infusion. Patients with comorbid PTSD and CP experienced less dissociative side effects compared to the CP group. Surprisingly, ketorolac infusion resulted in dissociative symptoms in CP patients only. Conclusions This first prospective study comparing effects of subanesthetic ketamine versus ketorolac infusions for comorbid PTSD and CP, suggests that both ketamine and ketorolac might offer meaningful and durable response for both PTSD and CP symptoms.

scholarly journals Analgesic effects of intravenous ketamine after spinal anaesthesia for non-elective caesarean delivery: a randomised controlled trial

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e044168
Author(s):  
Prahlad Adhikari ◽  
Asish Subedi ◽  
Birendra Prasad Sah ◽  
Krishna Pokharel
Keyword(s):  
Postoperative Pain ◽  
Adverse Effects ◽  
Outcome Measures ◽  
Caesarean Delivery ◽  
Low Dose ◽  
Saline Group ◽  
Secondary Outcome ◽  
Pain Scores ◽  
Intravenous Ketamine ◽  
Elective Caesarean Delivery

ObjectivesThis study aimed to determine if low dose intravenous ketamine is effective in reducing opioid use and pain after non-elective caesarean delivery.DesignProspective, randomised, double-blind.SettingTertiary hospital, Bisheshwar Prasad Koirala Institute of Health Sciences, Dharan, NepalParticipants80 patients undergoing non-elective caesarean section with spinal anaesthesia.InterventionsPatients were allocated in 1:1 ratio to receive either intravenous ketamine 0.25 mg/kg or normal saline before the skin incision.Primary and secondary outcome measuresThe primary outcome was the total amount of morphine equivalents needed up to postoperative 24 hours. Secondary outcome measures were postoperative pain scores, time to the first perception of pain, maternal adverse effects (nausea, vomiting, hypotension, shivering, diplopia, nystagmus, hallucination) and neonatal Apgar score at 1 and 5 min, neonatal respiratory depression and neonatal intensive-care referral.ResultsThe median (range) cumulative morphine consumption during the first 24 hours of surgery was 0 (0–4.67) mg in ketamine group and 1 (0–6) mg in saline group (p=0.003). The median (range) time to the first perception of pain was 6 (1–12) hours and 2 (0.5–6) hours in ketamine and saline group, respectively (p<0.001). A significant reduction in postoperative pain scores was observed only at 2 hours and 6 hours in the ketamine group compared with placebo group (p<0.05). Maternal adverse effects and neonatal outcomes were comparable between the two groups.ConclusionsIntravenous administration of low dose ketamine before surgical incision significantly reduced the opioid requirement in the first 24 hours in patients undergoing non-elective caesarean delivery.Trial registration numberNCT03450499.

Ingestion of Low Dose Pyroglutamyl Leucine Improves Dextran Sulfate Sodium-Induced Colitis and Intestinal Microbiota in Mice

2013 ◽  
Vol 61 (37) ◽  
pp. 8807-8813 ◽  
Author(s):  
Sayori Wada ◽  
Kenji Sato ◽  
Ryoko Ohta ◽  
Eri Wada ◽  
Yukiho Bou ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Low Dose ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium

scholarly journals COVID-19 and Mental Health: Predicted Mental Health Status is Associated with Clinical Symptoms and Pandemic-Related Psychological and Behavioral Responses

2021 ◽  
Author(s):  
Joyce Y Chung ◽  
Alison Gibbons ◽  
Lauren Atlas ◽  
Elizabeth Ballard ◽  
Monique Ernst ◽  
...  
Keyword(s):  
Mental Health ◽  
Health Status ◽  
Outcome Measures ◽  
Social Life ◽  
Clinical Symptoms ◽  
Behavioral Responses ◽  
Mental Health Status ◽  
Convenience Sample ◽  
Social Distancing ◽  
The Relationship

Abstract Background: The COVID 19 pandemic led to dramatic threats to health and social life. Study objectives are to develop a prediction model leveraging subsample of known Patient/Controls and evaluate the relationship of predicted mental health status to clinical outcome measures and pandemic-related psychological and behavioral responses during lockdown (spring/summer 2020). Methods: Online cohort study conducted by National Institute of Mental Health Intramural Research Program. Convenience sample of English speaking adults (enrolled 4/4 to 5/16/20; n=1,992). Enrollment measures: demographics, clinical history, functional status, psychiatric and family history, alcohol/drug use. Outcome measures (enrollment and q2 weeks/6 months): distress, loneliness, mental health symptoms, and COVID 19 survey. NIMH IRP Patient/Controls survey responses informed assignment of Patient Probability Scores (PPS) for all participants. Regression models analyzed the relationship between PPS and outcome measures. Outcomes: Mean age 46.0, female (82.4%), white (88.9 %). PPS correlated with distress, loneliness, depression, and mental health factors. PPS associated with negative psychological responses to COVID 19. Worry about mental health (OR 1.46) exceeded worry about physical health (OR 1.13). PPS not associated with adherence to social distancing guidelines but was with stress related to social distancing and worries about infection of self/others. Interpretation: Mental health status (PPS) was associated with concurrent clinical ratings and COVID 19 specific negative responses. A focus on mental health during the pandemic is warranted, especially among those with mental health vulnerabilities. We will include PPS when conducting longitudinal analyses of mental health trajectories and risk and resilience factors that may account for differing clinical outcomes. Funding: NIMH (ZIAMH002922); NCCIH (ZIAAT000030)

scholarly journals Therapy of bronchial asthma in children: age-related aspects

2021 ◽  
pp. 113-122
Author(s):  
Natalia A. Geppe ◽  
Elena G. Kondiurina ◽  
Vera A. Reviakina ◽  
Aleksandr B. Malakhov ◽  
Natalia G. Kolosova
Keyword(s):  
Bronchial Asthma ◽  
Low Dose ◽  
Clinical Symptoms ◽  
Bronchial Obstruction ◽  
Shortness Of Breath ◽  
Treatment And Prevention ◽  
Age Related ◽  
Asthma In Children ◽  
Global Initiative ◽  
Effective Drugs

Bronchial asthma (BA) is a disease that is one of the most frequent chronic diseases of childhood. Characteristic clinical symptoms of BA are wheezing, cough, difficulty in breathing, shortness of breath and, of course, recurrent episodes of bronchial obstruction. They require mandatory clarification of family and individual allergoanamnesis, assessment of symptoms, differential diagnosis with other diseases that may occur with BA. The Global Initiative for the Treatment and Prevention of Bronchial Asthma (GINA 20202021) preserves and develops the ageappropriate approach to verification of diagnosis and therapy selection, which is supported in the Russian National Program "Bronchial Asthma in Children" and in the Russian clinical guidelines "Bronchial Asthma 2021 When the diagnosis of BA is made, therapy should be started as early as possible. Administration of low-dose inhaled glucocorticosteroids (IGCS) immediately after the diagnosis allows not only to control the inflammatory process, which is the basis of BA, but also to reduce the severity of exacerbations. IGCS are the most effective drugs for children of any age, they ensure control of the disease and reduce the risk of AD exacerbations.

scholarly journals Quantitative trait loci associated with susceptibility to therapy-related acute murine promyelocytic leukemia in hCG-PML/RARA transgenic mice

Blood ◽  
2008 ◽  
Vol 112 (4) ◽  
pp. 1434-1442 ◽  
Author(s):  
Ryan K. Funk ◽  
Taylor J. Maxwell ◽  
Masayo Izumi ◽  
Deepa Edwin ◽  
Friederike Kreisel ◽  
...  
Keyword(s):  
Quantitative Trait ◽  
Complex Trait ◽  
Myelogenous Leukemia ◽  
Mouse Strains ◽  
Spleen Weight ◽  
Nucleotide Polymorphisms ◽  
Treatment Regimens ◽  
Multiple Loci ◽  
Acute Myelogenous ◽  
Trait Locus

Abstract Therapy-related acute myelogenous leukemia (t-AML) is an important late adverse effect of alkylator chemotherapy. Susceptibility to t-AML has a genetic component, yet specific genetic variants that influence susceptibility are poorly understood. We analyzed an F2 intercross (n = 282 mice) between mouse strains resistant or susceptible to t-AML induced by the alkylator ethyl-N-nitrosourea (ENU) to identify genes that regulate t-AML susceptibility. Each mouse carried the hCG-PML/RARA transgene, a well-characterized initiator of myeloid leukemia. In the absence of ENU treatment, transgenic F2 mice developed leukemia with higher incidence (79.4% vs 12.5%) and at earlier time points (108 days vs 234 days) than mice in the resistant background. ENU treatment of F2 mice further increased incidence (90.4%) and shortened median survival (171 vs 254 days). We genotyped F2 mice at 384 informative single nucleotide polymorphisms across the genome and performed quantitative trait locus (QTL) analysis. Thirteen QTLs significantly associated with leukemia-free survival, spleen weight, or white blood cell count were identified on 8 chromosomes. These results suggest that susceptibility to ENU-induced leukemia in mice is a complex trait governed by genes at multiple loci. Improved understanding of genetic risk factors should lead to tailored treatment regimens that reduce risk for patients predisposed to t-AML.

Cyclophosphamide-Induced Facial Discomfort

1994 ◽  
Vol 28 (2) ◽  
pp. 197-199 ◽  
Author(s):  
Jane L. Kosirog-Glowacki ◽  
Linda R. Bressler
Keyword(s):  
Outcome Measures ◽  
Teaching Hospital ◽  
Ipratropium Bromide ◽  
Clinical Symptoms ◽  
Nasal Congestion ◽  
University Teaching ◽  
Anticholinergic Medication ◽  
Mucous Membranes ◽  
Cyclophosphamide Administration ◽  
Infusion Duration

OBJECTIVE: To report the occurrence of cyclophosphamide-induced facial discomfort in patients at our institution, to review previous literature reports, and to discuss possible methods of prevention. SETTING: An oncology clinic in a university teaching hospital. PATIENTS: From January 1990 to March 1993, 14 patients experienced uncomfortable sensations of the skin or mucous membranes associated with cyclophosphamide administration. Details pertaining to each patient are described. INTERVENTIONS: Initial interventions included changing the duration of infusion or concentration of cyclophosphamide. We postulated that an anticholinergic medication such as ipratropium bromide may prevent cyclophosphamide-induced facial discomfort. MAIN OUTCOME MEASURES: Changing the infusion duration or cyclophosphamide concentration or administering ipratropium bromide intranasally resulted in variable degrees of improvement. CONCLUSIONS: The number of cyclophosphamide reactions seen at our institution indicates that facial or scalp burning, oropharyngeal tingling, nasal congestion, rhinorrhea, sneezing, and/or lacrimation may occur more frequently than previously noted. Thus, careful questioning is necessary to determine whether these clinical symptoms are present and bothersome in patients treated with cyclophosphamide. Intranasal ipratropium bromide, as well as other measures to prevent or decrease the intensity of cyclophosphamide-induced facial discomfort should be investigated.

Cellular basis for genetically determined enhanced resistance of certain mouse strains to listeriosis

1980 ◽  
Vol 28 (2) ◽  
pp. 381-386
Author(s):  
C Sadarangani ◽  
E Skamene ◽  
P A Kongshavn
Keyword(s):  
Bacterial Growth ◽  
Resistant Strain ◽  
Early Phase ◽  
Dextran Sulfate ◽  
Cellular Mechanism ◽  
Mononuclear Phagocytes ◽  
Susceptible Strain ◽  
Mouse Strains ◽  
Wide Range ◽  
Genetically Determined

The characteristics of the mononuclear phagocytes mediating resistance to infection with Listeria during the early phase (0 to 48 h) of the response have been investigated in genetically determined susceptible (A/J) and resistant (C57BL/6, B10.A/SgSn) strains of mice. Irradiation immediately before infection profoundly enhanced the bacterial growth in the resistant strain, while having no effect in the susceptible strain, over a wide range (3 x 10(3) to 10(5)) of infective doses. This effect of irradiation is demonstrable at low-dose radiation (200 roentgens) and can be reversed by repopulation with 20 x 10(6) syngeneic nucleated bone marrow cells. Administration of dextran sulfate 500 24 h before infection profoundly enhanced the bacterial growth in the susceptible strain, while having much less effect in the resistant strain. Thus, the genetic advantage of the resistant mouse strains to listerial infection, at least during the early phase of the response, appears to be due to a cellular mechanism that is highly radiosensitive and relatively insensitive to dextran sulfate 500. In the susceptible strain, the early protective cellular mechanism is radioresistant and highly dextran sulfate 500 sensitive.

AN OBSERVATIONAL STUDY OF THE CLINICAL PROFILE AND OUTCOMES OF PATIENTS WITH MILIARY TUBERCULOSIS (TB).

2021 ◽  
pp. 11-14
Author(s):  
Rajeev Tandon ◽  
Prabhat Kumar ◽  
Pradeep Nirala ◽  
Ansha Sinha
Keyword(s):  
Mortality Rate ◽  
Observational Study ◽  
Clinical Symptoms ◽  
Treatment Success ◽  
Miliary Tuberculosis ◽  
Time Duration ◽  
Drug Induced ◽  
Treatment Regimens ◽  
Standardized Treatment ◽  
Almost All

Objectives: This study aimed to evaluate the clinical prole and outcome of the patients with miliary tuberculosis (TB). Methods: This was a retrospective observational study which involved evaluation of medical records of 44 patients with miliary TB in the department of respiratory medicine and internal medicine from 2016-2019. Miliary TB in these patients had been diagnosed on the basis of clinical symptoms, radiology and microbiology. The clinical prole of the patients in terms of age, gender, clinical presentations were recorded. Time duration for resolution of symptoms was noted. Radiological outcome was also studied. Final outcome was treatment success and mortality. Results: The mean age of the patients were 37.07 years with 27 males. Most common complaints were fever (86.36%), cough (72.73%), expectoration (65.91%) and anorexia (45.45%). Laboratory ndings showed hypertransaminasemia, anemia, and hyponatremia in 75.00%, 70.45%, and 43.18% patients, respectively. Standardized treatment (RHEZ) was given in 70.45% patients, and non-standardized treatment in 29.55% patients. Median duration of fever was relieved in 15 days. Mortality rate was 11.36% and drug induced liver injury (DILI) was seen in 4(9.09%) patients. Radiological resolution was seen in almost all of the patients except in 3 and in majority of patients clearing was seen within the rst two months of initiation of treatment. Among all variables, hyperbilirubinemia showed signicant association with mortality (OR=14.6, 95% CI 1.86 to 114.615, P=0.013). Conclusion: In conclusion, in our series miliary TB presents most commonly in the third decade of life and is predominant among males. The clinical features were similar to pulmonary tuberculosis. There was frequent association with derangements in liver function, electrolyte, and hemoglobin. Hyperbilirubinemia was associated with signicantly increased the odds of mortality. Non-standardized treatment regimens were associated with poorer outcome. Mortality rate in miliary TB was as high as 11.3% in our series.

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