Effect of magnesium on arrhythmia incidence in patients undergoing coronary artery bypass grafting

Background

Cardiac arrhythmia after coronary artery bypass grafting (CABG) surgery is a common complication of cardiac surgery. The effect of serum magnesium, hypomagnesaemia treatment and prophylactic administration of magnesium in the development and prevention of arrhythmias is controversial and there are many different ideas. This study evaluates the therapeutic effects of magnesium in cardiac arrhythmia after CABG surgery.

Methods

The clinical trial enrolled 250 patients who underwent CABG. Based on the initial serum levels of magnesium, patients were divided into two groups: hypomagnesium and normomagnesium. Based on bioethics committee requirements, patients in the hypo-magnesium group received magnesium treatments until they attained normal magnesium blood levels. Both groups underwent CABG with normal blood levels of magnesium. After surgery, each group was randomly divided into two subgroups: one subgroup received a bolus dose of magnesium sulphate (30 mg/kg in 5 min) and the other subgroup received a placebo. Subgroups were under observation in the intensive care unit for 3 days and arrhythmias were recorded. Data from all four subgroups were analysed statistically and interpreted.

Results

The results of this study showed that the occurrence of arrhythmia was not significantly different among subgroups (P > 0.05). There was no significant relationship between blood levels of magnesium and arrhythmia during the 3 days post-surgery (P > 0.05).

Conclusion

The results of this study showed that magnesium sulphate administration did not significantly improve the incidence of arrhythmias in hypo- and normo-magnesium patients after CABG. There was no significant correlation between post-operative serum levels of magnesium and arrhythmia during 3 days.

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Evolution of bacterial virulence

Abstract

Bacterial virulence is highly dynamic and context-dependent. For this reason, it is challenging to predict how molecular changes affect the growth of a pathogen in a host and its spread in host population. Two schools of thought have taken quite different directions to decipher the underlying principles of bacterial virulence. While molecular infection biology is focusing on the basic mechanisms of the pathogen–host interaction, evolution biology takes virulence as one of several parameters affecting pathogen spread in a host population. We review both approaches and discuss how they can complement each other in order to obtain a comprehensive understanding of bacterial virulence, its emergence, maintenance and evolution.

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The Future of Basic Science in Academic Surgery: Identifying Barriers to Success for Surgeon-scientists

Objective: The aim of this study was to examine the challenges confronting surgeons performing basic science research in today's academic surgery environment. Summary of Background Data: Multiple studies have identified challenges confronting surgeon-scientists and impacting their ability to be successful. Although these threats have been known for decades, the downward trend in the number of successful surgeon-scientists continues. Clinical demands, funding challenges, and other factors play important roles, but a rigorous analysis of academic surgeons and their experiences regarding these issues has not previously been performed. Methods: An online survey was distributed to 2504 members of the Association for Academic Surgery and Society of University Surgeons to determine factors impacting success. Survey results were subjected to statistical analyses. We also reviewed publicly available data regarding funding from the National Institutes of Health (NIH). Results: NIH data revealed a 27% decline in the proportion of NIH funding to surgical departments relative to total NIH funding from 2007 to 2014. A total of 1033 (41%) members responded to our survey, making this the largest survey of academic surgeons to date. Surgeons most often cited the following factors as major impediments to pursuing basic investigation: pressure to be clinically productive, excessive administrative responsibilities, difficulty obtaining extramural funding, and desire for work-life balance. Surprisingly, a majority (68%) did not believe surgeons can be successful basic scientists in today's environment, including departmental leadership. Conclusions: We have identified important barriers that confront academic surgeons pursuing basic research and a perception that success in basic science may no longer be achievable. These barriers need to be addressed to ensure the continued development of future surgeon-scientists.

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Why are patients with blood cancers more likely to die without hospice?

BACKGROUND

Although patients with blood cancers have significantly lower rates of hospice use than those with solid malignancies, data explaining this gap in end-of-life care are sparse.

METHODS

In 2015, we conducted a mailed survey of a randomly selected sample of hematologic oncologists in the United States to characterize their perspectives regarding the utility and adequacy of hospice for blood cancer patients, as well as factors that might impact referral patterns. Simultaneous provision of care for patients with solid malignancies was permitted.

RESULTS

We received 349 surveys (response rate, 57.3%). The majority of respondents (68.1%) strongly agreed that hospice care is helpful for patients with hematologic cancers; those with practices including greater numbers of solid tumor patients (at least 25%) were more likely to strongly agree (odds ratio, 2.10; 95% confidence interval, 1.26-3.52). Despite high levels of support for hospice in general, 46.0% felt that home hospice is inadequate for their patients' needs (as compared to inpatient hospice with round-the-clock care). Although more than half of the respondents reported that they would be more likely to refer patients to hospice if red cell and/or platelet transfusions were available, those who considered home hospice inadequate were even more likely to report that they would (67.3% vs 55.3% for red cells [P = .03] and 52.9% vs 39.7% for platelets [P = .02]).

CONCLUSIONS

These data suggest that although hematologic oncologists value hospice, concerns about the adequacy of services for blood cancer patients limit hospice referrals. To increase hospice enrollment for blood cancer patients, interventions tailoring hospice services to their specific needs are warranted. Cancer 2017. © 2017 American Cancer Society.

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Multidisciplinary management of metastatic melanoma to the inter-atrial septum

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Comparison of 5-year oncological outcomes of breast cancer based on surgery type

Background

A standardized classification system for breast surgery that incorporates oncoplastic techniques is needed. We classified the surgical techniques for breast cancer treatment into five groups according to the extent of surgery and reconstructive methods, i.e. conventional breast-conserving surgery, partial mastectomy with volume displacement, partial mastectomy with volume replacement, simple mastectomy and total mastectomy with immediate reconstruction. We then evaluated the oncological outcomes for each of the five groups.

Methods

We analysed clinical data and 5-year oncological results from patients with breast cancer who underwent breast surgery with reconstruction between 2008 and 2013. Local recurrence, distant metastasis and overall survival were investigated.

Results

In total, 1469 patients had 1504 breast surgeries performed with a mean follow-up of 72.40 ± 16.76 months. There were 35 cases (2.3%) of locoregional recurrence and 85 cases (5.7%) of distant metastasis, and the 5-year overall survival rate was 98.6%. No statistically significant differences were observed in local recurrence, distant metastasis or death among the five surgical technique groups (P = 0.218, 0.518 and 0.450, respectively).

Conclusion

Oncological outcomes among all patients and within each surgical technique group were excellent during the 5-year follow-up period. No significant differences in oncological results were observed among the five surgical technique groups.

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A novel K+ competitive acid blocker, YH4808, sustains inhibition of gastric acid secretion with a faster onset than esomeprazole: randomised clinical study in healthy volunteers

Summary

Background

YH4808, a K⁺-competitive acid blocker, is under clinical development for the treatment of acid-related disorders, such as gastroesophageal reflux disease.

Aims

We aimed to determine the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of YH4808, compared to placebo and esomeprazole.

Methods

This double-blind, randomised, placebo- and active comparator (esomeprazole)-controlled study was conducted with 123 healthy male volunteers. We evaluated YH4808 (30-800 mg) properties, administered in single (N=55) and multiple (N=24) oral doses, and recorded the effects on 24-hour intragastric acidity. Results were compared to placebo (N=20) and esomeprazole 40 mg (N=24).

Results

Plasma YH4808 exposure increased dose-proportionally and declined in a multi-phasic manner. YH4808 ≥200 mg/d maintained intragastric acidity at pH >4 for longer times than esomeprazole during both day and night (%Time at pH >4: >70% vs 58% of a 24-hour period, respectively; and >50% vs 33% of a 9-hour night respectively). A twice-daily regimen of YH4808 more effectively controlled intragastric pH at night than a once-daily regimen. In evaluating the mean areas under the intragastric pH-time curves in 15-minute intervals for 2 hours after dosing, we found that YH4808 had a faster onset than esomeprazole. Moreover, unlike esomeprazole, YH4808 PK and PD were not significantly affected by the CYP2C19 genotype of the subjects. YH4808 was well-tolerated at all doses administered.

Conclusion

This study showed that YH4808 produced a rapid, sustained suppression of gastric secretion with good tolerability. The results at YH4808 ≥200 mg/d provide a rationale for further clinical investigations in populations with acid-related diseases.

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Review article: recent insights into clinical decision-making in severe alcoholic hepatitis

Summary

Background

Alcoholic hepatitis is a severe acute manifestation of alcoholic liver disease with a high mortality. Management of patients with this condition has been a matter of controversy for many years; however, recent clinical studies have sought to improve the clinical approach to these patients.

Aim

To use these recent studies in order to guide clinical management.

Methods

A MeSH search of Medline was performed to specifically identify recent studies which influenced clinical diagnosis, assessment and management of alcoholic hepatitis.

Results

Fulfilment of clear clinical criteria including a minimum threshold of bilirubin, defined periods of jaundice and alcohol ingestion negates the need for liver biopsy in most patients. Corticosteroids improve short-term mortality only (28 day) with other factors such as abstinence likely to be significant in long-term outcome. Pentoxifylline is not an effective treatment. The Glasgow Alcoholic Hepatitis Score (GAHS) score can identify those patients likely to benefit from corticosteroids, but scores that include the evolution of bilirubin over 1 week of such treatment (such as the Lille Score) define "response". Underlying infection may contribute towards corticosteroid nonresponse and needs to be actively sought out and treated. Liver transplant remains controversial; however, it has been shown to be feasible in alcoholic hepatitis.

Conclusions

Recent studies have helped to define patients who may benefit from corticosteroid treatment. However, there remains a need for more accurate scores of prognosis and treatment response, and a clear need for alternative treatments for those patients not responding to corticosteroid therapy.

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Sleep convulsive seizures predict lack of remission in genetic generalized epilepsies: A retrospective study from a single epilepsy center in Egypt

Background

Genetic generalized epilepsies (GGEs) represent 15-20% of all epilepsies. There are no studies on the outcome of GGEs in the Middle East.

Aims

To investigate the long-term prognosis of GGEs and identify prognostic predictors in Egypt.

Material & Methods

This is a retrospective cohort study of consecutive children and adults with GGEs seen in an epilepsy clinic in Cairo, Egypt, followed for 10+ years. Follow-up visits were scheduled every 3-6 months or earlier. Demographic and clinical prognostic predictors were collected. Presence and number of seizure types were noted along with the number and doses of drugs. The outcome was defined as 5-year remission (5yrR), relapse, or no remission. The probability of 5yrR was calculated using Kaplan-Meier curves. Prognostic predictors were assessed with Cox proportional models.

Results

Included were 120 patients (males, 41.7%), mean age at onset 13.6 years, followed for a mean of 12.5 years (range 10-20). Generalized tonic-clonic seizures were present in 93.3% of cases, followed by myoclonic (65%) and absence seizures (37.5%). 85 cases (70.8%) attained 5yrR (18 of them off-medications) and 59.1% had a relapse. The cumulative probability of starting 5yrR was 6.7%, 30.8%, and 50% at onset, 5 and 10 years. Only absence of sleep seizures was an independent predictor of 5yrR (Hazard ratio, 2.08; 95% CI 1.01-4.33).

Discussion

Our findings are in keeping with others. The negative effects of sleep seizures are not unexpected because further unrecognized seizures might be expected.

Conclusions

Prolonged remission of GGEs is high and compatible with treatment discontinuation. Sleep seizures are negative prognostic predictors.

http://ift.tt/2rGyQRG

A Novel Approach for Early Evaluation of Orthodontic Process by a Numerical Thermo-Mechanical Analysis

Summary

The main objective of this paper is to propose a novel method that provides an opportunity to evaluate an orthodontic process at early phase of the treatment. This was accomplished by finding out a correlation between the applied orthodontic force and thermal variations in the tooth structure. To this end, geometry of the human tooth surrounded by the connective soft tissue called the periodontal ligament and the bone was constructed by employing dental CT scan images of a specific case. The periodontal ligament was modeled by finite strain viscoelastic model through a nonlinear stress-strain relation (hyperelasticity) and nonlinear stress-time relation (viscoelasticity). The tooth structure was loaded by a lateral force with fifteen different quantities applied to twenty different locations, along the mid-edge of the tooth crown. The resultant compressive stress in the periodontal ligament was considered as the cause of elevated cell activity that was modeled by a transient heat flux in the thermal analysis. The heat flux value was estimated by conducting an experiment on a pair of rats. The numerical results showed that by applying an orthodontic force to the tooth structure, a significant temperature rise was observed. By measuring the temperature rise, the orthodontic process can be evaluated.

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MicroRNA-29b Contributes to Collagens Imbalance in Human Osteoarthritic and Dedifferentiated Articular Chondrocytes

Objective. Decreased expression of collagen type II in favour of collagen type I or X is one hallmark of chondrocyte phenotype changes in osteoarthritic (OA) cartilage. MicroRNA- (miR-) 29b was previously shown to target collagens in several tissues. We studied whether it could contribute to collagen imbalance in chondrocytes with an impaired phenotype. Methods. After preliminary microarrays screening, miR-29b levels were measured by RT- quantitative PCR in in vitro models of chondrocyte phenotype changes (IL-1β challenge or serial subculturing) and in chondrocytes from OA and non-OA patients. Potential miR-29b targets identified in silico in 3′-UTRs of collagens mRNAs were tested with luciferase reporter assays. The impact of premiR-29b overexpression in ATDC5 cells was studied on collagen mRNA levels and synthesis (Sirius red staining) during chondrogenesis. Results. MiR-29b level increased significantly in IL-1β-stimulated and weakly in subcultured chondrocytes. A 5.8-fold increase was observed in chondrocytes from OA versus non-OA patients. Reporter assays showed that miR-29b targeted COL2A1 and COL1A2 3′-UTRs although with a variable recovery upon mutation. In ATDC5 cells overexpressing premiR-29b, collagen production was reduced while mRNA levels increased. Conclusions. By acting probably as a posttranscriptional regulator with a different efficacy on COL2A1 and COL1A2 expression, miR-29b can contribute to the collagens imbalance associated with an abnormal chondrocyte phenotype.

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Alzheimer’s disease: the state of the art in resting-state magnetoencephalography

Worldwide, approximately 35.6 million people are estimated to have dementia (WHO, 2012). Dementia prevalence ranges between 1.6% and 6.4% in subjects over age 60 and increases disproportionally with advancing age (Ferri et al., 2005). Alzheimer's disease (AD) is the most common form of dementia and is known to be accompanied by abnormal neuronal activity that has been linked to amyloid beta depositions between neurons (Bero et al 2011; Walker and Jucker, 2011). Although studies have indicated several potentially modifiable risk factors for AD (Norton et al., 2014), at this moment, no curative interventions are available.

http://ift.tt/2qadw57

Complications of Temporomandibular Joint Surgery

Gary F. Bouloux Description This book provides detailed guidance on the recognition and treatment of the complications most frequently encountered in patients who undergo temporomandibular joint surgery. Evidence-based guidelines are... Read more »

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Physiologic Anchorage Control 2017 : A New Orthodontic Concept and its Clinical Application

Tian Min Xu Description This book provides a comprehensive introduction to physiologic anchorage control, explains the implications for clinical practice, and presents an anchorage technique applicable for the treatment of... Read more »

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Salivary Gland Development and Regeneration : Advances in Research and Clinical Approaches to Functional Restoration

Seunghee Cha Description This book provides a comprehensive update on the latest information and knowledge which emerged from translational and basic science research endeavors, targeting the regeneration of salivary glands.... Read more »

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Clinical Guide to Accelerated Orthodontics : With a Focus on Micro-Osteoperforations

Mani Alikhani Description This book is a complete reference for all clinicians who are interested in incorporating into their daily practice the techniques available to reduce the duration of orthodontic... Read more »

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Dental Fear and Anxiety in Pediatric Patients 2017 : Practical Strategies to Help Children Cope

Caroline Campbell Description This book is a comprehensive guide to pediatric dental fear/anxiety (DFA) and phobia that will provide practitioners with a full understanding of the etiology, prevalence, assessment, and... Read more »

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Sport and Oral Health : A Concise Guide

Jean-christophe Egea Description This book aims to explore the intricate interrelationship between oral health and sport, with the focus on highly popular team games, endurance sports, and explosive events. In... Read more »

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Time to Treatment and Mortality during Mandated Emergency Care for Sepsis

More than 1.5 million cases of sepsis occur in the United States annually, and many patients with sepsis present to the emergency department. International clinical practice guidelines and the Centers for Medicare and Medicaid Services (CMS) recommend the prompt identification of sepsis and…

http://ift.tt/2qIxg3M

State Sepsis Mandates — A New Era for Regulation of Hospital Quality

Sepsis is a major cause of illness and death in the United States, affecting more than 1.5 million Americans each year at an annual cost of over $20 billion. To improve outcomes of sepsis, policymakers are increasingly using regulatory mechanisms intended to provide incentives to clinicians and…

http://ift.tt/2rGOXht

State Sepsis Mandates — A New Era for Regulation of Hospital Quality

Sepsis is a major cause of illness and death in the United States, affecting more than 1.5 million Americans each year at an annual cost of over $20 billion. To improve outcomes of sepsis, policymakers are increasingly using regulatory mechanisms intended to provide incentives to clinicians and…

http://ift.tt/2rGOXht

Time to Treatment and Mortality during Mandated Emergency Care for Sepsis

More than 1.5 million cases of sepsis occur in the United States annually, and many patients with sepsis present to the emergency department. International clinical practice guidelines and the Centers for Medicare and Medicaid Services (CMS) recommend the prompt identification of sepsis and…

http://ift.tt/2qIxg3M

State Sepsis Mandates — A New Era for Regulation of Hospital Quality

Sepsis is a major cause of illness and death in the United States, affecting more than 1.5 million Americans each year at an annual cost of over $20 billion. To improve outcomes of sepsis, policymakers are increasingly using regulatory mechanisms intended to provide incentives to clinicians and…

http://ift.tt/2rGOXht

Angiotensin II for the Treatment of Vasodilatory Shock

Shock is a life-threatening syndrome characterized by decreased organ perfusion that can progress to irreversible organ failure. Vasodilatory shock is the most common type of shock and is characterized by peripheral vasodilation and reduced blood pressure despite preserved cardiac output.…

http://ift.tt/2rGAAtC

MET overexpression and gene amplification: prevalence, clinico-pathological characteristics and prognostic significance in a large cohort of patients with surgically resected NSCLC

Abstract

The prevalence of overexpression and amplification of the proto-oncogene mesenchymal epithelial transition (MET) in non-small cell lung cancer (NSCLC) varies greatly in the literature. Since MET is a potential treatment target, knowledge of its prevalence and prognostic importance is crucial. We investigated MET expression and gene status in 735 NSCLC cases using tissue microarrays. Prognostic significance as well as correlations with various clinico-pathological parameters were evaluated. The prevalence of MET overexpression was 17% and MET amplification was present in 2.4% of cases. MET overexpression was found more frequently in adenocarcinomas (and TTF1-positive tumors) and female patients and was also associated with expression of members of the epidermal growth factor receptor (EGFR) signaling cascade. MET amplified tumors tended to express MET more frequently and more intensively. MET expression or gene status did not prove to be relevant prognostic factors. MET may not be an unequivocal prognostic parameter; however, its expression is associated with certain clinico-pathological characteristics and with EGFR and downstream EGFR effectors. This could be an important point for future studies addressing targeted MET therapy and should be considered as a possible means of optimizing the benefit and minimizing undesirable effects.

http://ift.tt/2qEIC8s

Full-root Aortic Valve Replacement by Stentless Aortic Xenografts in Patients with Small Aortic Roots

Full-root aortic valve replacement by stentless aortic xenograft is a viable option in patients with small aortic roots. We describe, a technique for the full-root implantation of stentless aortic xenografts, with emphasis on the management of the proximal suture line and coronary anastomoses, and discuss its limitations and alternative options.

http://ift.tt/2pZM4vN

Uncontrolled Hemorrhagic Shock Modeled via Liver Laceration in Mice with Real Time Hemodynamic Monitoring

Uncontrolled hemorrhage, an important cause of mortality among trauma patients, can be modeled using a standard liver laceration in a murine model. This model results in consistent blood loss, survival, and allows for testing hemostatic agents. This article provides the step-by-step process to perform this valuable model.

http://ift.tt/2qLLcIx

Hashimoto’s Encephalopathy Presenting with Unusual Behavioural Disturbances in an Adolescent Girl

Hashimoto's encephalopathy (HE) is a rare autoimmune disorder with neurological and neuropsychiatric manifestations and elevated titres of anti-thyroid antibodies. Here we are reporting a case of HE in a 19-year-old girl who presented with seizure-like episodes, confusion, and behavioural disturbances with catatonic symptoms such as posturing, echopraxia, echolalia, and ambivalence. Patient did not respond to antipsychotics and anticonvulsants. On further investigation, patient was found to have high serum anti-TPO antibodies of about 1261 U/mL with euthyroid status, which supported a suspicion of HE. Our consultant neurologist confirmed the diagnosis and she was started on injection of methylprednisolone 750 mg OD. Since patient started showing clinical improvement, her antipsychotic medications were tapered off. On follow-up, patient has recovered and is functioning well. Since HE is a diagnosis of exclusion, very high anti-TPO antibodies and good response to steroids supported the diagnosis of HE in this patient after excluding other etiological possibilities. This case has been reported because the clinical presentation was predominantly neurobehavioural manifestations which is uncommon with HE.

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A Constellation of Rare Findings in a Case of Goldenhar Syndrome

An 18-month-old child presented with right macrostomia, bilateral preauricular skin tags, bilateral CTEV, squint in bilateral eyes, thoracic vertebral anomalies, right sided aortic arch, and associated left pulmonary agenesis. The patient did not have any associated respiratory symptoms. Ipsilateral pulmonary agenesis is considered as a rare association with Goldenhar syndrome and a case of contralateral pulmonary aplasia has been described as an even rarer association.

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Effects of Radix Astragali and Its Split Components on Gene Expression Profiles Related to Water Metabolism in Rats with the Dampness Stagnancy due to Spleen Deficiency Syndrome

Radix Astragali (RA) with slight sweet and warm property is a significant "qi tonifying" herb; it is indicated for the syndrome of dampness stagnancy due to spleen deficiency (DSSD). The purpose of this research was to explore effects of RA and its split components on gene expression profiles related to water metabolism in rats with the DSSD syndrome for identifying components representing property and flavor of RA. The results indicated that RA and its split components, especially polysaccharides component, significantly increased the body weight and the urine volume and decreased the water load index of model rats. Our data also indicated differentially expressed genes (DEGs) related to water metabolism involved secretion, ion transport, water homeostasis, regulation of body fluid levels, and water channel activity; the expression of AQP1, AQP3, AQP4, AQP5, AQP6, and AQP8 was improved; calcium, cAMP, MAPK, PPAR, AMPK, and PI3K-Akt signaling pathway may be related to water metabolism. In general, results indicate that RA and its split components could promote water metabolism in rats with the DSSD syndrome via regulating the expression of AQPs, which reflected sweet-warm properties of RA. Effects of the polysaccharides component are better than others.

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Gastrodia elata Blume Rhizome Aqueous Extract Improves Arterial Thrombosis, Dyslipidemia, and Insulin Response in Testosterone-Deficient Rats

Testosterone deficiency deteriorates glucose and lipid metabolism with reducing muscle mass. We investigated whether the consumption of water extracts of Gastrodia elata Blume rhizome (GEB) rich in gastrodin would reduce the symptoms of testosterone deficiency and improve blood flow in orchidectomized (ORX) rats. ORX rats were given high-fat diets supplemented with either 1% cellulose (ORX-control), 0.3% GEB (GEB-L), or 1% GEB (GEB-H) for 8 weeks. Sham-operated rats were fed the same diet as OVX-control rats (normal-control). ORX-control rats had reduced serum testosterone levels by one-fifth, compared to normal-control rats. ORX-control rats exhibited decreased lean body mass, attenuated blood flow, and impaired cholesterol metabolism and glucose control due to decreased insulin secretory response. GEB increased serum insulin levels dose-dependently and GEB-H mostly enhanced dyslipidemia in ORX rats. GEB completely normalized arterial thrombosis time and blood flow in ORX rats. Interestingly, ORX-control rats showed attenuated hepatic insulin signaling but greater AMPK and CREB activities, which reduced triglyceride accumulation, compared to normal-control. GEB-H improved hepatic insulin signaling but maintained the AMPK and CREB activities in ORX rats. In conclusions, GEB ameliorated the impairment of cholesterol and glucose metabolism and blood flow in ORX rats. GEB may be a potential preventive measure for reducing the risk of cardiovascular diseases associated with testosterone deficiency.

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Treatment of Cervical Artery Dissection: Antithrombotics, Thrombolysis, and Endovascular Therapy

Cervical artery dissection (CAD) is an important cause of stroke for young patients, accounting for 5–22% of strokes in patients

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The Protective Effect of N-Acetylcysteine on Ionizing Radiation Induced Ovarian Failure and Loss of Ovarian Reserve in Female Mouse

Ionizing radiation may cause irreversible ovarian failure, which, therefore, calls for an effective radioprotective reagent. The aim of the present study was to evaluate the potential radioprotective effect of N-acetylcysteine (NAC) on ionizing radiation induced ovarian failure and loss of ovarian reserve in mice. Kun-Ming mice were either exposed to X-irradiation (4 Gy), once, and/or treated with NAC (300 mg/kg), once daily for 7 days before X-irradiation. We examined the serum circulating hormone levels and the development of ovarian follicles as well as apoptosis, cell proliferation, and oxidative stress 24 hours after X-irradiation. In addition, morphological observations on the endometrial luminal epithelium and the fertility assessment were performed. We found that NAC successfully restored the ovarian and uterine function, enhanced the embryo implantation, improved the follicle development, and altered the abnormal hormone levels through reducing the oxidative stress and apoptosis level in granulosa cells while promoting the proliferation of granulosa cells. In conclusion, the radioprotective effect of NAC on mice ovary from X-irradiation was assessed, and our results suggested that NAC can be a potential radioprotector which is capable of preventing the ovarian failure occurrence and restoring the ovarian reserve.

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Prostate cancer-related anxiety in long-term survivors after radical prostatectomy

Abstract

Purpose

Knowledge of the psychological distress of long- and very long-term (>10 years) prostate cancer (PC) survivors is limited. This study intended to examine the parameters influencing anxiety related to prostate-specific antigen (PSA) and PC in long-term survivors after radical prostatectomy.

Methods

We surveyed 4719 PC survivors from the German multicenter prospective database "Familial Prostate Cancer." We evaluated the association of PC-related anxiety (MAX-PC) with sociodemographic characteristics, family history of PC, global health status/quality of life (EORTC QLQ-C30), depression and anxiety (PHQ-2; GAD-2), latest PSA level, time since radical prostatectomy, and current therapy.

Results

The survey participants' mean age was 75.2 years (SD = 6.5). Median follow-up was 11.5 years, and 19.5% of participants had survived more than 15 years since the initial treatment. The final regression analysis found that younger age, lower global health status/quality of life, higher depression and anxiety scores, higher latest PSA level, and shorter time since radical prostatectomy predicted increased PSA-related anxiety and PC anxiety. Familial PC was predictive only of PSA anxiety (all p < 0.05). The final model explained 12% of the variance for PSA anxiety and 24% for PC anxiety.

Conclusions

PC-related anxiety remained relevant many years after prostatectomy and was influenced by younger age, psychological status, rising PSA level, and shorter time since initial treatment.

Implications for Cancer Survivors

Survivors with these characteristics are at increased risk of PC-related anxieties, which should be considered by the treating physician during follow-up.

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Are you smarter than the average paramedic? Test your EMS smarts!

Take our 10-question quiz to test your knowledge, then share your results and challenge your colleagues to prove their expertise

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Hemodialysis does not impact axitinib exposure: clinical case of a patient with metastatic renal cell carcinoma

Abstract

Axitinib is approved with indication in patients with advanced renal cell carcinoma (RCC). Due to the localization of this cancer, physicians sometimes have to deal with hemodialyzed patients. Data exploring hemodialysis (HD) impact on axitinib pharmacokinetic (PK) or safety are lacking. To date, no data have been published on that problematic. This is the first publication discussing the assessment of axitinib PK for a patient undergoing HD. Our results suggest that there is no influence of HD on axitinib blood concentration. Interestingly, the membranes used are common and represent around 90% of the membranes used in routine for HD. Our data are also reassuring both from activity and from safety perspectives. In that case, axitinib administered at a dose of 6 mg twice a day was well tolerated and allowed 12 months of disease control. These results are in line with previous publications discussing other anti-angiogenic tyrosine kinase inhibitors pharmacokinetics, safety and activity among patients with metastatic RCC undergoing hemodialysis.

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The incidence and risk factors of febrile neutropenia in chemotherapy-naïve lung cancer patients receiving etoposide plus platinum

Abstract

Purpose

This study was to determine the incidence and risk factors of febrile neutropenia in chemotherapy-naïve Japanese patients treated systemically with etoposide plus platinum for lung cancer.

Methods

The study was a retrospective analysis of 244 patients who were monitored for febrile neutropenia through multiple cycles of the combination of etoposide with platinum, and the associations between incidence of febrile neutropenia and patient characteristics were evaluated.

Results

Eighty-eight patients were treated with etoposide plus cisplatin and 156 were treated with etoposide plus carboplatin. Of the 244 patients treated, 198 (81.1%) completed 4 cycles for chemotherapy. Febrile neutropenia was observed in 48 of 244 patients (19.7%), including 18 of 88 (20.5%) patients who received etoposide plus cisplatin and 30 of 156 (19.2%) patients who received etoposide plus carboplatin. Grade 3 or 4 of neutropenia was experienced by a total of 208 patients (85.2%); 79 of 88 (89.8%) receiving etoposide plus cisplatin and 129 of 156 (82.7%) receiving etoposide plus carboplatin. Male gender and previous radiotherapy were identified by multivariate analysis as independent risk factors for febrile neutropenia.

Conclusions

These results contrast with findings in Western patients and suggest that ethnic differences exist in the incidence of febrile neutropenia in patients receiving etoposide plus platinum chemotherapy. In addition, our results suggest that primary prophylaxis with granulocyte colony-stimulating factor should be considered for patients with these risk factors for febrile neutropenia prior to treatment with etoposide plus platinum.

http://ift.tt/2q898nd

Enhancing the therapeutic range of a targeted small-molecule tubulysin conjugate for folate receptor-based cancer therapy

Abstract

Purpose

EC0305 represents a folate-tubulysin B construct capable of specifically eradicating folate receptor (FR)-positive subcutaneous tumors from mice (Leamon et al., Cancer Res 68:9839–9844, 8). Herein we report on the use of multiple polar carbohydrate segments (e.g. 1-amino-1-deoxy-glucitolyl-γ-glutamate) placed in-between the folate and tubulysin B moieties of EC0305 creating a new conjugate, herein referred to as EC0531, with more desirable biological properties.

Methods

The synthesis of EC0531 and its tritium-labeled counterpart are described. EC0531's affinity for FR binding and specific cytotoxic activity was assessed using standard in vitro assays. Human tumor xenografts were used to directly compare EC0305 and EC0531's antitumor activity. Finally, bile duct cannulated, female Sprague–Dawley rats were used to compare hepatobiliary clearance of these two targeted chemotherapeutic agents.

Results

EC0531 tightly binds to the FR with an affinity about half that of folic acid. It was found to specifically inhibit the growth of FR⁺ cells (IC₅₀ of ~2 nM) in a dose-dependent manner. Using ³H-labeled compounds, more than a 12-fold higher amount of tubulysin was measured in a FR + human tumor xenograft compared to the unconjugated drug, a finding that explains, in part, why EC0531 displays curative activity, whereas the unconjugated tubulysin agent is essentially inactive. EC0531 was found to produce greater FR-specific anti-tumor activity at lower dose levels than EC0305; furthermore, EC0531's maximum tolerated dose level was significantly higher than that of EC0305, likely because EC0531's saccharopeptidic-based spacer allows for ~sixfold reduction in hepatic clearance.

Conclusions

These data provide additional evidence that the therapeutic range of targeted small-molecule drug conjugates can be favorably increased using molecular spacers constructed with 1-amino-1-deoxy-glucitolyl-γ-glutamate residues.

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Paclitaxel-induced sensory peripheral neuropathy is associated with an ABCB1 single nucleotide polymorphism and older age in Japanese

Abstract

Purpose

Whether age and inter-individual variability of pharmacogenetics are risk factors for paclitaxel-induced peripheral neuropathy (PIPN) is inconclusive. This study was conducted to evaluate the influence of previously investigated single nucleotide polymorphisms (SNPs) and age, using genotype data from a prospective study of paclitaxel-related toxicity in Japanese patients with breast cancer.

Methods

Peripheral blood mononuclear cells from 127 Japanese women with breast cancer who received weekly adjuvant paclitaxel were used to genotypes SLCO1B3 T334G (rs4149117), CYP2C8 A1196G (rs10509681), ABCB1 C1236T (rs1128503), ABCB1 G2677T/A (rs2032582), and ABCB1 C3435T (rs1045642). Genotypic and clinical factors were investigated for associations with PIPN.

Results

Of the five SNPs evaluated, no SNPs were significantly associated with grade 2 or higher PIPN. However, ABCB1 1236 TT showed a trend to associate with grade 2 or higher PIPN compared to ABCB1 CT/CC (odds ratio 2.1, 95% CI 0.991–4.548, p = 0.051). In subgroup analysis, patients ≥60 years old with an ABCB1 1236 TT had a higher incidence of ≥grade 2 PIPN compared to patients with CT or CC genotype (p = 0.027). On multivariable analysis, age ≥60 years and the ABCB1 1236 TT showed a significant association with ≥grade 2 PIPN (p = 0.005 and p = 0.034, respectively).

Conclusions

ABCB1 1236 TT genotype and older age might be a predictor of PIPN, which diminishes quality of life of cancer survivors.

http://ift.tt/2q83VvP

Neurotoxicity after high-dose methotrexate (MTX) is adequately explained by insufficient folinic acid rescue

Abstract

Purpose

To challenge the view that the dose of folinic acid rescue after high-dose methotrexate (MTX) has no significance in the prevention of neurotoxicity and to present the minority view that neurotoxicity can be prevented by an adequate dose of folinic acid, without compromising treatment results. Several fallacies that led to the misunderstanding of post MTX neurotoxicity are presented.

Methods

Data mining using search engines was used to find relevant publications, and an e-mail survey of more than 60 authors of articles in this field was performed. All relevant articles identified were read in their entirety.

Results

Examples of clinical studies with neurotoxicity following inadequate rescue are given. Some studies demonstrated no neurotoxicity when adequate doses of folinic acid rescue were started 24–36 h after the start of HDMTX rescue even after mega doses of MTX. Rescue started after 42 h was associated with neurotoxicity except in patients with low serum MTX levels after 24 and 36 h. ALL protocols with neurotoxicity, especially BFM-like protocols, are presented. Protocol is reported in which single protocol changes prevented neurotoxicity.

Conclusions

From the published data, when folinic acid rescue is given in a sufficiently high enough dose and is started 24–36 h after the beginning of the methotrexate exposure, and virtually all forms of post MTX neurotoxicity can be prevented without compromising therapeutic results.

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Phase II study of S-1 plus bevacizumab combination therapy for patients previously treated for non-squamous non-small cell lung cancer

Abstract

Purpose

To assess the efficacy and toxicity of S-1 and bevacizumab combination therapy for patients previously treated for advanced non-squamous non-small cell lung cancer (NSCLC).

Methods

This was a prospective, multi-center, single-arm phase II study. Patients with non-squamous NSCLC who had experienced progression after cytotoxic chemotherapy were enrolled. Oral S-1 was administered on days 1–14 of a 21-day cycle, and bevacizumab (15 mg/kg) was given intravenously on day 1. Patients received S-1 adjusted on the basis of their creatinine clearance and body surface area. The primary endpoint was response rate (RR); secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety.

Results

We enrolled 30 patients. One patient had never received platinum-based therapy. Five patients had activating mutations of the epidermal growth factor receptor gene, of whom four had received tyrosine kinase inhibitors before this study. The RR was 6.7% [95% confidence interval (CI) 1.8–21.3%], and the disease control rate (DCR) was 80% (95% CI 62.7–90.5%). Median PFS was 4.8 months (95% CI 2.7–6.4 months], and median OS was 13.8 months (95% CI 8.4 months–not applicable). Patients did not experience any Grade 4 toxicity or treatment-related death. Grade 3 hematologic toxicity (anemia) occurred in one patient (3.3%). The main Grade 3 non-hematologic toxicities were anorexia (10%), infection (10%), and diarrhea (6.7%).

Conclusion

The addition of bevacizumab to S-1 was tolerable, but not beneficial for patients with previously treated non-squamous NSCLC. We do not recommend further study of this regimen.

http://ift.tt/2q80uFd

MITF suppression by CH5552074 inhibits cell growth in melanoma cells

Abstract

Purpose

Although treatment of melanoma with BRAF inhibitors and immune checkpoint inhibitors achieves a high response rate, a subset of melanoma patients with intrinsic and acquired resistance are insensitive to these therapeutics, so to improve melanoma therapy other target molecules need to be found. Here, we screened our chemical library to identify an anti-melanoma agent and examined its action mechanisms to show cell growth inhibition activity.

Methods

We screened a chemical library against multiple skin cancer cell lines and conducted ingenuity pathway analysis (IPA) to investigate the mechanisms of CH5552074 activity. Suppression of microphthalmia-associated transcription factor (MITF) expression levels was determined in melanoma cells treated with CH5552074. Cell growth inhibition activity of CH5552074 was evaluated in MITF-dependent melanoma cell lines.

Results

We identified an anti-melanoma compound, CH5552074, which showed remarkable cell growth inhibition activity in melanoma cell lines. The IPA results suggested that CH5552074-sensitive cell lines had activated MITF. In further in vitro studies in the melanoma cell lines, a knockdown of MITF with siRNA resulted in cell growth inhibition, which showed that CH5552074 inhibited cell growth by reducing the expression level of MITF protein.

Conclusions

These results suggest that CH5552074 can inhibit cell growth in melanoma cells by reducing the protein level of MITF. MITF inhibition by CH5552074 would be an attractive option for melanoma treatment.

http://ift.tt/2qDfTBd

In vitro and in vivo assessments of two novel hydrazide compounds against breast cancer as well as mammary tumor cells

Abstract

Purpose

The hydrazide backbone is a well-known structural core system found in a broad range of biologically activated compounds. Among which, the compounds with anticancer activity have been cited in a number of studies. With this object in mind, we focused on the in vitro and in vivo anticancer potential of two novel hydrazide derivatives bearing furan or thiophen substituents (compounds 1 and 2).

Methods

The cytotoxic property was evaluated using MTT assay against MCF-7 human breast adenocarcinoma cell line, while the in vivo antitumor activity was investigated in BALB/c mice bearing 4T1 mammary carcinoma cells. Flow cytometry was used for cell cycle analysis, and detection of apoptosis was examined by Annexin-V-FLUOS/PI assay. Protein expression of Bax, Bcl-2 and procaspase-3 was estimated by Western blotting.

Results

Compounds 1 and 2 were found to be cytotoxic towards breast cancer cells presenting IC₅₀ values of 0.7 and 0.18 µM, respectively, and selectivity over normal fibroblast cells. Our findings further indicated that 2 × IC₅₀ concentrations of both compounds induce early stage apoptosis and increase percentage of sub-G1 population in MCF-7 cells at 48 h. An elevation in Bax/Bcl-2 ratio and caspase-3 cleavage suggested that apoptosis induced by the two compounds is through a caspase- and mitochondrial-dependent pathway. In the in vivo study, compounds 1 and 2 at doses of 10 and 1 mg/Kg/day, respectively, significantly hindered the growth of tumor after 3 weeks of i.p. administration, when compared to vehicle-treated mice.

Conclusion

Collectively, the great potential exhibited by compound 2 could make it a promising chemotherapeutic candidate for human cancers, especially for breast cancer.

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Adjuvant concurrent chemoradiotherapy with low-dose daily cisplatin for extrahepatic bile duct cancer

Abstract

Purpose

We aimed to present the clinical outcomes of adjuvant concurrent chemoradiotherapy (CCRT) with low-dose daily cisplatin regimen compared to the conventional 5-fluorouracil (5-FU)-based regimen for extrahepatic bile duct cancer (EHBDC).

Methods

From October 1994 to April 2013, 41 patients received adjuvant CCRT with low-dose daily regimen or 5-FU-based regimens. Nineteen patients received low-dose of cisplatin just before every delivery of radiation therapy, and 21 patients received two cycles of 5-FU-based regimen during radiotherapy. We compared the clinical outcomes between two adjuvant CCRT regimens.

Results

Adjuvant CCRT with low-dose daily cisplatin showed comparable toxicity profiles compared with that of a 5-FU-based regimen. The median follow-up time was 33 months (range, 5–205), and the 5-year overall survival (OS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) were 34.2, 50.8, and 49.7%, respectively. Univariable analyses showed no significant differences in OS, LRRFS, and DMFS between the groups with two regimens. In multivariable analyses, chemotherapeutic regimen was a significant prognostic factor for OS, favoring the low-dose daily cisplatin regimen (HR = 2.491, p = 0.036) over 5-FU-based regimen, though not for LRRFS (p = 0.642) and DMFS (p = 0.756).

Conclusions

Adjuvant CCRT with low-dose daily cisplatin regimen showed acceptable toxicities and survivals compared to those of the 5-FU-based regimen. Low-dose daily cisplatin can be one of the feasible regimens for adjuvant CCRT for EHBDC.

http://ift.tt/2q84Wns

Massage Therapy in Children with Asthma: A Systematic Review and Meta-Analysis

Objective. To systematically evaluate the efficacy of massage, a traditional treatment method of traditional Chinese medicine on children with asthma. Methods. Literatures from 5 databases using the date ranging from 1 January, 1990, to 13 December, 2016, were reviewed, which were all randomized controlled trials evaluating the efficacy on children with asthma and effect on lung function mainly by massage therapy. Results. 14 researches with 1299 patients were included in the meta-analysis. Compared with control group, a better efficacy was found in treatment group, which focused on massage therapy. Compared with control group, there was remarkable increase on FEV1 as well as PEF in treatment group. Conclusion. All studies have shown that massage therapy has a significantly positive effect on children with asthma, improves the pulmonary function parameters of large airway, reduces the plasma concentrations of PAF and prostaglandin, and increases the levels of PAF-AH and DP1; therefore, it greatly improves pulmonary function. However, the limited research designs of included studies lead to high risk of bias. More randomized controlled trials with better methodological quality are needed to further confirm the effectiveness of massage.

http://ift.tt/2rpZOQk

Optimal Branching Structure of Fluidic Networks with Permeable Walls

Biological and engineering studies of Hess-Murray's law are focused on assemblies of tubes with impermeable walls. Blood vessels and airways have permeable walls to allow the exchange of fluid and other dissolved substances with tissues. Should Hess-Murray's law hold for bifurcating systems in which the walls of the vessels are permeable to fluid? This paper investigates the fluid flow in a porous-walled T-shaped assembly of vessels. Fluid flow in this branching flow structure is studied numerically to predict the configuration that provides greater access to the flow. Our findings indicate, among other results, that an asymmetric flow (i.e., breaking the symmetry of the flow distribution) may occur in this symmetrical dichotomous system. To derive expressions for the optimum branching sizes, the hydraulic resistance of the branched system is computed. Here we show the T-shaped assembly of vessels is only conforming to Hess-Murray's law optimum as long as they have impervious walls. Findings also indicate that the optimum relationship between the sizes of parent and daughter tubes depends on the wall permeability of the assembled tubes. Our results agree with analytical results obtained from a variety of sources and provide new insights into the dynamics within the assembly of vessels.

http://ift.tt/2q5R1PG

Extremely Low-Frequency Electromagnetic Fields Affect Myogenic Processes in C2C12 Myoblasts: Role of Gap-Junction-Mediated Intercellular Communication

Extremely low-frequency electromagnetic fields (ELF-EMFs) can interact with biological systems. Although they are successfully used as therapeutic agents in physiatrics and rehabilitative practice, they might represent environmental pollutants and pose a risk to human health. Due to the lack of evidence of their mechanism of action, the effects of ELF-EMFs on differentiation processes in skeletal muscle were investigated. C2C12 myoblasts were exposed to ELF-EMFs generated by a solenoid. The effects of ELF-EMFs on cell viability and on growth and differentiation rates were studied using colorimetric and vital dye assays, cytomorphology, and molecular analysis of MyoD and myogenin expression, respectively. The establishment of functional gap junctions was investigated analyzing connexin 43 expression levels and measuring cell permeability, using microinjection/dye-transfer assays. The ELF-EMFs did not affect C2C12 myoblast viability or proliferation rate. Conversely, at ELF-EMF intensity in the mT range, the myogenic process was accelerated, through increased expression of MyoD, myogenin, and connexin 43. The increase in gap-junction function suggests promoting cell fusion and myotube differentiation. These data provide the first evidence of the mechanism through which ELF-EMFs may provide therapeutic benefits and can resolve, at least in part, some conditions of muscle dysfunction.

http://ift.tt/2q5JkJd

HIPK2 Overexpression and Its Prognostic Role in Human Papillomavirus-Positive Tonsillar Squamous Cell Carcinoma

Tonsillar squamous cell carcinomas (TSCCs) are the most common human papillomavirus- (HPV-) associated oropharyngeal cancers with poor prognosis. Homeodomain-interacting protein kinase 2 (HIPK2) is a central regulator of p53, which participates in apoptosis during the DNA damage response. HIPK2 is involved in HPV-associated uterine cervical and cutaneous carcinogenesis through its binding of HPV E6, thereby preventing apoptosis and contributing to tumor progression. However, its clinical and prognostic significance in TSCC remains unclear. HIPK2 mRNA levels were analyzed in 20 normal tonsils and 20 TSCC specimens using real-time reverse transcription polymerase chain reaction. Immunohistochemistry of HIPK2 was performed in 79 resected specimens. HIPK2 was expressed in 57% of the TSCCs, and HIPK2 protein expression and HIPK2 mRNA levels were higher in TSCCs than in normal tonsils. HIPK2 overexpression was associated with poorly differentiated carcinoma and low alcohol consumption and was an independent prognostic factor for overall survival and disease-free survival (DFS) in TSCC and a negative independent prognostic factor for DFS in patients receiving postoperative radiotherapy. HIPK2 overexpression had a significant association with poorer DFS in HPV-positive TSCCs, but not in HPV-negative tumors. HIPK2 overexpression may be a potential prognostic marker for predicting prognoses and a high risk of recurrence, particularly in patients with HPV-positive TSCC.

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Editorial Board/Publication information

Publication date: June 2017
Source:Injury, Volume 48, Supplement 1





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Comparing the Vitex-castus extract and cabergoline effects on estrous induction in female dogs

Abstract

Cabergoline is used to induce estrus, stop lactation, and induce abortion in small animals. The specific doses of Vitagnus extract have almost identical properties of cabergoline that reduce prolactin and increase the concentration of FSH hormone. The aim of this study was to compare the effect of Vitex agnus-castus extract and cabergoline on prolactin concentration and hormonal changes associated with the onset of estrous cycle in dogs. Twelve healthy adult cyclic female-mix breed dogs were selected and randomly aligned in treatment (6 dogs, Vitagnus extract 1.5 ml daily for 5 weeks, 80–90 mg/ml, PO) and control groups (6 dogs, cabergoline, daily for 5 weeks, 5 μg/kg, PO). Blood sampling and vaginal smears were taken weekly. Serum samples were stored at −20 °C until prolactin, estradiol, and progesterone were measured by ELISA method. Based on vaginal cytology results, four (cabergoline) and three (Vitagnus) dogs were in the estrous phase after 5 weeks of treatment. The average concentration of the prolactin was not changed during 5 weeks and between two groups. There was no significant difference in progesterone and estradiol levels between groups. The changes of estradiol concentration were significant during the 5 weeks (p < 0.01). The mean concentration of this hormone changed significantly between weeks 2 and 3 (p < 0.01), 2 and 5 (p < 0.05), and 3 and 4 (p < 0.05). In conclusion, Vitagnus extract had hormonal effects similar to those of cabergoline for induction of estrus in bitches.

http://ift.tt/2qH4ZL0