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Serotonin and sympathomimetic toxicity (SST) after ingestion of amphetamine-based drugs can lead to severe morbidity and death. There have been evaluations of the safety and efficacy of on-site treatment protocols for SST at music festivals.
The study aimed to examine the safety and efficacy of treating patients with SST on-site at a music festival using a protocol adapted from hospital-based treatment of SST.
The study is an audit of presentations with SST over a one-year period. The primary outcome was need for ambulance transport to hospital. The threshold for safety was prospectively defined as less than 10% of patients requiring ambulance transport to hospital.
The protocol suggested patients be treated with a combination of benzodiazepines; cold intravenous (IV) fluid; specific therapies (cyproheptadine, chlorpromazine, and clonidine); rapid sequence intubation; and cooling with ice, misted water, and convection techniques.
One patient of 13 (7.7%) patients with mild or moderate SST required ambulance transport to hospital. Two of seven further patients with severe SST required transport to hospital.
On-site treatment may be a safe, efficacious, and efficient alternative to urgent transport to hospital for patients with mild and moderate SST. The keys to success of the protocol tested included inclusive and clear education of staff at all levels of the organization, robust referral pathways to senior clinical staff, and the rapid delivery of therapies aimed at rapidly lowering body temperature. Further collaborative research is required to define the optimal approach to patients with SST at music festivals.
Stereotactic body radiation therapy for lung tumours can expose patients to radiation pneumonitis (RP) (<6 months after irradiation) and lung fibrosis (beyond 6 months). The aim of this study was to describe post-irradiation radiographics appearances.
Materials and methods:
This retrospective study of 90 patients with a stage I non-small cell lung carcinoma reports a detailed description of the computed tomography (CT) or positron emission tomography/CT changes that can be observed after treatment, according to modified Kimura score for RP and Koenig’s classification for fibrosis. This evaluation was realised at 1 month and then every 3–4 months, with a median follow-up of 35 months.
The most common radiological RP pattern was diffuse consolidation. It appears in a mean time of 4 months and reaches its maximum at 9 months after radiotherapy. Seventy-three per cent of the RP evolved to fibrosis. Most of these findings were encompassed in the 35 Gy isodose.
Radiological parenchymal changes are frequent in the treatment region, which renders the tumour response monitoring by tumour size, particularly by response evaluation criteria in solid tumours, unsuitable.
Paraquat) was the most successful non-selective herbicide in Korea due to its rapid herbicidal activity. However, its high mammalian toxicity, frequent self-poisoning incidents and lack of effective antidotes have led to a paraquat ban in Korea in 2012. Therefore, this review was conducted to revisit the toxicological profile of paraquat and to investigate the impacts of the paraquat ban on human health and agriculture in Korea. A review on toxicological information reconfirmed that paraquat is highly acute toxic to human, while ingestion, inhalation or dermal administration of the herbicide can cause severe clinical signs, and inevitably leads to death by respiratory failure. In Korea, the paraquat ban immediately decreased the suicide rate due to pesticides (mainly paraquat) by 46.1%, resulting in a 10% decrease of total suicide rate. However, this also led to an increase in suicide attempts with other poisonings such as carbon monoxide, suggesting that suicide attempts and rates with poisoning depend not only on the toxicity of poisoning but also the accessibility to the poisoning agents. In agriculture, paraquat was quickly replaced by other non-selective herbicides such as glufosinate and glyphosate. Thus, the paraquat ban did not give a significant impact on agricultural practices but influenced the non-selective herbicide market, the use of glufosinate was higher than glyphosate due to its rapid herbicidal activity, similar to paraquat. Though the paraquat ban can be considered as a national strategy to lower suicide rates, the increase in suicide attempts with other poisonings suggests that multilateral efforts are required for not only keeping suicidal agents away from people but also minimizing motives for suicide.
The current drugs for Chagas disease treatment present several limitations
The sesquiterpene lactone goyazensolide (GZL) was evaluated regarding to cytotoxicity and trypanocidal activity against amastigotes, selectivity index (SI) in vitro, acute toxicity and anti-Trypanosoma cruzi activity in vivo.
The in vitro cytotoxicity in H9c2 cells was observed at doses >250 ng mL−1 of GZL and the SI were of 52.82 and 4.85 (24 h) and of 915.00 and 41.00 (48 h) for GZL and BZ, respectively. Nephrotoxicity and hepatotoxicity were not verified. Treatment with GZL of mice infected with CL strain led to a significant decrease of parasitaemia and total survival at doses of 1 and 3 mg kg−1 day−1 by oral and IV, respectively. This last group cured 12.5% of the animals (negativation of HC, PCR, qPCR and ELISA). Animals infected with Y strain showed significant decrease of parasitaemia and higher negativation in all parasitological tests in comparison to BZ and control groups, but were ELISA reactive, as well as the BZ group, but mice treated with 5.0 mg kg−1 day−1 by oral were negative in parasitological tests and survived.
GZL was more active against T. cruzi than benznidazole in vitro and presented important therapeutic activity in vivo in both T. cruzi strains.
Arsenic (As) is highly toxic element, even at very low concentrations in feed and drinking water. Its physiological role in poultry is well established, as it is essential for the synthesis of methionine metabolites including cysteine, even though it is a teratogenic and carcinogenic element. Paradoxically, recent studies have uncovered its nutritional value. The recommended amounts of As in poultry feed are between 0.012 and 0.050 mg/kg. Water is the primary route for the transfer of As and exposure of animals to its toxic effects. The available data on the impact of water contamination on the deposition of As in broiler tissues are rather scarce. The amount of As was 0.006-0.015 mg/kg in breast meat, 0.007-0.017 mg/kg in drumstick meat, 0.001-0.014 mg/kg in liver and 0.008-0.016 mg/kg in testicles of broilers at the end of a 42 day experiment after exposure to naturally contaminated drinking water. The toxic dose of As for poultry is between 40 and 50 mg/kg of poultry feed whereas the amount of 40 mg/kg leads to decreased egg production and the amount of 50 mg/kg leads to decreased feed consumption. Symptoms of chronic As exposure differ among individuals, populations and geographic regions, which suggests that there is no universal definition of symptoms associated with chronic As poisoning. Moreover, some individuals can tolerate high As, that is, levels that can be fatal for others. In wild birds, the content of As was the highest in meat of march hens (0.063 mg/kg), seagull muscle tissue (0.058 mg/kg), in meat from swans (0.022 mg/kg) and the white-tailed eagle (0.022 mg/kg). In this review, the essential role and toxicity of As in poultry nutrition is addressed with particular emphasis on its importance as a contaminant of poultry feed and products.
The incidence of breast cancer has surpassed cervical cancer in India and it has now become the most common cancer in women. Multiple randomised studies have reported low α/β value in the range of 3–4 for breast cancer, which predict a potential radiobiological advantage for hypofractionated radiotherapy resulting in such schedules becoming standard in many centers with reduction in overall treatment time. Volumetric modulated arc therapy (VMAT) is a novel technique of delivering radiotherapy that reduces treatment delivery time, requires less monitor units (MU) and offers good conformity. The mean dose to normal tissue may be minimised using this technique although there will be inferior sparing if we consider the low-dose volume such as V5, the effect of which is not quantifiable yet.
Reporting acute toxicity, cosmetic effects, and quality of life in patients of early breast cancer treated with adjuvant hypofractionated VMAT with SIB.
Material and Methods:
The records of 44 patients registered at the hospital between August 2014 and December 2015 were included in this analysis. Acute toxicities were analysed using CTCAE v4.03. Cosmetic outcomes were assessed using Harvard scale, while quality of life outcomes were assessed using EORTC scales and Health Related quality of life (HRQOL) questionnaires (QLQ-C30 and QLQ-BR23).
No grade ≥2 skin toxicities were recorded. Breast pain was recorded as Grade 1 in 13·8% patients and Grade 1 fatigue in 18·2%. The maximum haematological abnormality grade recorded was Grade 1. Cosmesis was assessed at the baseline, 6 months, 1 year and 2 years. A total of 88·6% of the patients had an Excellent or good cosmesis at the baseline, which was similar even at 6 months, at 88·7%, improved further at 1 year to 90·9%. At 6 months post radiotherapy, high functional scale QOL scores were noted.
The technique is associated with minimum acute toxicity, good to excellent cosmesis and acceptable quality of life.
To determine associations between household food security status and risk of Cu toxicity.
A population-level cross-sectional study to determine adult household food security status and its relationship with serum total Cu concentration (serum Cu) using multivariable regression models.
Adult participants in the US National Health and Nutrition Examination Survey (NHANES) 2011–2014.
The NHANES phlebotomy data, a nationally representative sample (n 2780; 1360 men and 1420 women), were analysed.
A significantly greater proportion of food-insecure persons had serum Cu that was above the upper value of the normal range (clinical cut-off) compared with their food-secure counterparts. In men, food insecurity (OR = 2·24, P < 0·001) and marginal food security (OR = 1·79, P < 0·001), and in women, marginal food security (OR = 1·82, P = 0·016), associated with greater likelihood to have serum Cu that was above the upper value of the normal range. Food insecurity was significantly associated with greater likelihood (OR = 1·65, P = 0·020) to have serum Cu that was within the upper quartile (≥75th centile).
Food-insecure persons associate with higher serum Cu concentration and are at greater risk of Cu toxicity. There is need to study the sources of Cu in general, and specifically in food-insecure persons, to facilitate reduction of Cu exposure. Examining Cu contents of the food and water supplies could explicate any relationships to food insecurity and Cu intake.
Studies have shown that daily exposure to different products, whether chemical or natural, can cause irreversible damage to women’s reproductive health. Therefore it is necessary to use tests that evaluate the safety and efficacy of these products. Most reproductive toxicology tests are performed in vivo. However, in recent years, various cell culture methods, including embryonic stem cells and tissues have been developed with the aim of reducing the use of animals in toxicological tests. This is a major advance in the area of toxicology, as these systems have the potential to become a widely used tool compared with in vivo tests routinely used in reproductive biology and toxicology. The present review describes and highlights data on in vitro culture processes used to evaluate reproductive toxicity as an alternative to traditional methods using in vivo tests.
The purpose of this study was to investigate variations in surface dose, with and without the use of a Klarity® Mask (Orfit Industries America, Wijnegem, Belgium), using intensity-modulated radiotherapy (IMRT) and 3-D conventional radiotherapy (3D-CRT).
Materials and methods
Thermoluminescent dosimeters (TLDs) together with a phantom were used to examine acute skin toxicity during nasopharyngeal cancer treatment. These plans were sequentially delivered to the perspex phantom. Dosimeters were placed in five fixed regions over the skin. A Klarity mask for immobilization was used for covering the head, neck, and shoulder. The phantom was irradiated with and without a Klarity Mask, using IMRT and 3D-CRT, respectively.
The Klarity mask increased the skin doses for IMRT and 3D-CRT approximately 18·6% and 8·6%, respectively, from the prescribed maximum skin dose using treatment planning system (TPS). Additionally, the average percentage dose between IMRT and 3D-CRT received on the surface region was 30·9%, 24·9% with and without Klarity mask respectively. The average percentage dose received on surfaces from the total therapeutic dose 70 Gy, without using the mask was 7·7% and 5·7%, for IMRT and 3D-CRT, respectively. The TPS overestimated the skin dose for IMRT planning by 20%, and for 3D-CRT by 16·6%, compared with TLD measurements.
The results of this study revealed that IMRT significantly increases acute skin toxicity, compared with CRT. Although it is recommended to use Klarity mask as a sparing tool of normal tissue, it increases the risk of skin toxicity. In conclusion, skin dose is an important issue of focus during radiotherapy.
To evaluate the survival outcomes and toxicities experienced by non-metastatic head and neck cancer (HNC) patients receiving modulated radiotherapy (RT).
Materials and methods
A total of 608 HNC patients treated consecutively from March 2010 to December 2014 with common subsites (oral cavity, oropharynx, hypopharynx, larynx and nasopharynx) of HNCs formed the study group. Eligible patients included those treated with radical or postoperative RT between March 2010 and December 2014. More than 90% patients received modulated RT [intensity-modulated radiotherapy (IMRT) or volumetric-modulated arc therapy (VMAT)] with concurrent chemotherapy as per stage guidelines. Demographic parameters and disease-related factors were analysed. Disease-free survival (DFS) was calculated from end date of RT till last follow-up or last date of disease control. Overall survival (OS) was calculated from date of registration to last follow-up date if alive. The primary endpoint was survival. The statistical analyses were performed using SPSS version 20.0 and Kaplan–Meier method was used for calculation survival.
Among the evaluable patients, the median age was 60 years (range: 16–93) with male preponderance (male:female – 513:95). Majority were squamous cell carcinoma 93·4% (568/608). The subsites treated were oral cavity 36·8% (224). oropharynx 26·4% (161), larynx 19·7% (120), hypopharynx 10% (62) and nasopharynx 6·4% (41). RT intent was radical in 63·5% (386) and postoperative in 36·5% (222), with 59·5% (362) receiving concurrent chemotherapy. At last follow-up, 348 (57·2%) patients were alive, 169 (27·7%) patients had succumbed to disease and 120 (24·6%) patients had recurrent disease. Out of 120 recurrent cases loco-regional recurrence, nodal recurrence and distant metastases were seen in 62 (51·7%), 25 (20·8%), 33 (27·5%), respectively. In the entire study cohort at 2 year OS and DFS was 80 and 79% whereas 3 years OS and DFS was 70 and 75%, respectively.
In our study, 2 years and 3 years OS and DFS rates are found comparable to the international data with acceptable toxicity profile with the use of modulated RT. It seems to be possible because of stringent departmental protocols and good medical physics support. Our data re-validates need and benefit of advanced RT techniques like IG-IMRT and VMAT for both postoperative and radical HNC treatment at the cost of minimal long-term side effects. Future stringent follow-up and quality of life issues are being considered in a prospective manner.
Efficacious therapeutic strategies against lymphatic filariasis are always sought after. However, natural products are a promising resource for developing effective antifilarial agents. Azadirachtin, a significant tetranortriterpenoid phytocompound found in Azadirachta indica, was evaluated in vitro for antifilarial potential against the filarial parasite Setaria cervi. Dye exclusion and MTT assay confirmed the antifilarial potential of azadirachtin against S. cervi with a median lethal dose (LC50) of 6.28 μg/ml for microfilariae (mf), and 9.55 μg/ml for adult parasites. Morphological aberrations were prominent in the histological sections of the azadirachtin-exposed parasites. Moreover, alterations in the reactive oxygen species (ROS) parameters in treated parasites were evident. Induction of apoptosis in treated parasites was confirmed by DNA laddering, acridine orange (AO)/ethidium bromide (EtBr) double staining and in situ DNA fragmentation. The downregulation of anti-apoptotic CED-9 and upregulation of proapoptotic EGL-1, CED-4 and CED-3 at both the transcription and translation levels confirmed apoptosis execution at the molecular level. Changes in the gene expressions of nuc-1, cps-6 and crn-1 further clarified the molecular cause of DNA degradation. Furthermore, azadirachtin was found to be non-toxic in both in vitro and in vivo toxicity analyses. Therefore, the experimental evidence detailed the pharmacological effectiveness of azadirachtin as a possible therapeutic agent against filariasis.
Attempts have been made in recent years to reduce the use of synthetic pesticides and seek alternative and innovative methods for pest control. We conducted a study on the chemical composition of Eucalyptus occidentalis essential oil and investigated the fumigant, contact and repellent effects against Tribolium castaneum (Herbst) (Col: Tenebrionidae) and Rhyzopertha dominica (F.) (Col: Bostrichidae). The major components were τ-cadinol (17.20), 1,8-cineol (15.5%), α-cadinol (14%) and α-pinene (9.21%). The contact toxicity experiment showed that the oil was more toxic to R. dominica (LD50 value 0.82 μL/cm) than to T. castaneum (LD50 value 0.99 μL/cm) and showed the same fumigant toxicity for both insects according to the 95% confidence limit of LC50. The repellency against T. castaneum was more than for R. dominica and increased from 14 to 75% for R. dominica and 22 to 78% for T. castaneum after 2 h. These results suggest that E. occidentalis essential oil is a potential candidate for use as a natural repellent and insecticide for stored-product insect pests.
High BMI is associated with an increased risk of breast cancer in post-menopausal women but poorer outcomes in all age groups. The underlying mechanism is likely to be multi-factorial. Patients with a high BMI may present later due to body habitus. Some studies have also indicated an increased incidence of biologically adverse features, including a higher frequency of oestrogen receptor (ER negative) tumours, in obese patients. Obese patients have a higher frequency of surgical complications, potentially delaying systemic therapies, and reports suggest that chemotherapy and endocrine therapy are less effective in patients with BMI ≥30 kg/m2.
High BMI is generally interpreted as excess adiposity and a World Cancer Research Fund report judged that the associations between BMI and incidence of breast cancer were due to body fatness. However, BMI cannot distinguish lean mass from fat mass, or characterise body fat distribution. Most chemotherapy drugs are dosed according to calculated body surface area (BSA). Patients with a similar BSA or BMI may have wide variations in their distribution of adipose tissue and skeletal muscle (body composition); however, few studies have looked at the effect of this on chemotherapy tolerance or effectiveness. Finally, adjuvant treatments for breast cancer can themselves result in body composition changes.
Research is required to fully understand the biological mechanisms by which obesity influences cancer behaviour and the impact of obesity on treatment effectiveness and tolerance so that specific management strategies can be developed to improve the prognosis of this patient group.
This study assessed the anthelmintic activity of plant-derived compounds against gastrointestinal nematodes of goats using the egg hatch and larval motility assays. The compounds tested were saponins (digitonin and aescin) and their respective sapogenins (aglycones), hecogenin acetate and flavonoids (catechin, hesperidin, isocordoin and a mixture of isocordoin and cordoin). Additionally, cytotoxicity of active substances was analysed on Vero cell through 3-4,5-dimethylthiazol-2-yl,2,5diphenyltetrazolium bromide (MTT) and propidium iodide (PI) tests. Significant reduction on the egg hatching (P < 0.05) was seen only in the treatments with aescin (99%/EC50 = 0.67 mg mL−1) and digitonin (45%). The compounds that reduced the larval motility (P < 0.05) were digitonin (EC50 = 0.03 mg mL−1 and EC90 = 0.49 mg mL−1) and the hecogenin acetate (75%). The other sapogenins showed low anthelmintic activity. All the flavonoids showed low ovicidal (4–12%) and larvicidal (10–19%) effects. The aescin and digitonin showed low toxicity in PI test (viable cells >90%). Nevertheless, higher cytotoxicity was observed in the MTT assay, with IC50 of 0.20 mg mL−1 (aescin) and 0.0074 mg mL−1 (digitonin). Aescin and digitonin have a pronounced in vitro anthelmintic effect and the glycone portion of these saponins plays an important role in this activity.
To increase the corrosion prevention of stainless steel implant and fast recovery due to new bone-cell formation at the orthopedic implant site, in the present investigation, a trilayered (with bioceramic interlayer sandwiched between innermost passivated surface and outermost polymer coating) 316L stainless steel (SS) implant was designed and investigated. It was inferred that this new designed implant invokes faster and more bone-cell formation than uncoated commercially available 316L SS implants. Faster bone-cell formation at the coated implant site reduces the initial threat of implant corrosion. The electrochemical corrosion study proved that this model of coated implants is able to prevent corrosion up to 90% better than uncoated commercially available 316L SS. Subsequently, preclinical studies in the rabbit bone defect model (which included histology, radiology, fluorochrome labeling, push-out test, and scanning electron microscopy taken after 45 and 90 days) proved higher rate of new bone tissue formation and better push-out strength between tissue in contact and the coated implant. The toxicological study of vital organs like liver, kidney, and heart also exhibited no abnormality. The outcome of the experimentations indicates suitability of this trilayered 316L SS implant for bone repair and healing.
Advancements in image-based technologies and body composition research over the past decade has led to increased understanding of the importance of muscle abnormalities, such as low muscle mass (sarcopenia), and more recently low muscle attenuation (MA), as important prognostic indicators of unfavourable outcomes in patients with cancer. Muscle abnormalities can be highly prevalent in patients with cancer (ranging between 10 and 90 %), depending on the cohort under investigation and diagnostic criteria used. Importantly, both low muscle mass and low MA have been associated with poorer tolerance to chemotherapy, increased risk of post-operative infectious and non-infectious complications, increased length of hospital stay and poorer survival in patients with cancer. Studies have shown that systemic antineoplastic treatment can exacerbate losses in muscle mass and MA, with reported loss of skeletal muscle between 3 and 5 % per 100 d, which are increased exponentially with progressive disease and proximity to death. At present, no effective medical intervention to improve muscle mass and MA exists. Most research to date has focused on treating muscle depletion as part of the cachexia syndrome using nutritional, exercise and pharmacological interventions; however, these single-agent therapies have not provided promising results. Rehabilitation care to modify body composition, either increasing muscle mass and/or MA should be conducted, and its respective impact on oncology outcomes explored. Although the optimal timing and treatment strategy for preventing or delaying the development of muscle abnormalities are yet to be determined, multimodal interventions initiated early in the disease trajectory appear to hold the most promise.
Radiotherapy-induced damage to non-cancerous gastrointestinal mucosa has effects on secretory and absorptive functions and can interfere with normal gastrointestinal physiology. Nutrient absorption and digestion may be compromised. Dietary manipulation is an attractive option with sound rationale for intervention. The aim of this review was to synthesise published evidence for the use of elemental formulae, low or modified fat diets, fibre, lactose restriction and probiotics, prebiotics and synbiotics to protect the bowel from gastrointestinal side effects during long-course, radical pelvic radiotherapy. Thirty original studies (recruiting n 3197 patients) were identified comprising twenty-four randomised controlled trials, four cohort studies and two comparator trials. Endpoints varied and included symptom scales (Inflammatory Bowel Disease Questionnaire, Common Technology Criteria for Adverse Events, Radiation Therapy Oncology Group) and Bristol Stool Scale. Dietary and supplement interventions were employed with many studies using a combination of interventions. Evidence from RCT was weak for elemental, low or modified fat and low-lactose interventions and modestly positive for the manipulation of fibre during radiotherapy. Evidence for probiotics as prophylactic interventional agents was more promising with a number of trials reporting positive results but strength and strains of interventions vary, as do methodologies and endpoints making it difficult to arrive at firm conclusions with several studies lacking statistical power. This consolidated review concludes that there is insufficient high-grade evidence to recommend nutritional intervention during pelvic radiotherapy. Total replacement of diet with elemental formula could be effective in severe toxicity but this is unproven. Probiotics offer promise but cannot be introduced into clinical practice without rigorous safety analysis, not least in immunocompromised patients.
To evaluate the Klarity® Mask with respect to skin doses and toxicity secondary to head and neck cancer radiation treatment.
Materials and methods
This prospective study included five nasopharyngeal cancer patients who underwent intensity-modulated radiation therapy and monitored for skin toxicity. An anatomical Perspex head and neck phantom was designed and used. All patients’ treatment plans were separately transferred to the phantom. Dosimetric measurements were performed using chip-shaped thermoluminescent dosimeters (LiF:Mg,Ti TLDs) which were distributed at certain target points on the phantom. Phantom was irradiated twicely with and without a Klarity® Mask. Three fractions for each patient plan were obtained and compared with treatment planning system (TPS) doses as guided by computed tomography.
The Klarity mask used for patient immobilisation increased the surface dose by 10·83% more than that without the mask. The average variations between skin dose measurements with and without the Klarity mask for all patients’ plans ranged from 10·26 to 11·83%. TPS overestimated the surface dose by 19·13% when compared with thermoluminescent dosimeters that measured the direct skin dose.
Klarity immobilisation mask increases skin doses, as a consequence, surface dose measurements should be monitored and must be taken into account.