A prospective study to analyse the concentration of octenidine in hand wounds after disinfection by LC-MS/MS.

Toxic reactions can appear after pressurised flushing of soft tissue with octenidine (OCT) containing disinfectants. Their use for surgical disinfection could complicate the diagnosis of possible contamination. In patients with open lacerations of their hand's subcutaneous tissue samples were taken before and after surgical disinfection with Octenisept® and analysed by ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). In 16 out of 20 tissue samples, OCT was detected after disinfection (lower limit of quantification (LLOQ)=10 pg/mL/mg). The concentration of OCT was below the LLOQ, estimation of mean of 0.6 pg/mL/mg (0.22-0.98 pg/mL/mg, 95%-CI) before disinfection and mean of 179.4 pg/mL/mg (13.35-432.0 pg/mL/mg, 95%-CI) after disinfection. This study shows that the disinfection of open wounds with Octenisept® leads to a quantifiable concentration of OCT in open wounds. In cases of suspected OCT-mediated toxic reaction, the use of antiseptics containing OCT should be avoided.

Relationship between methylenetetrahydrofolate reductase gene polymorphisms and methotrexate drug metabolism and toxicity.

Background: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, and methotrexate (MTX) is the key drug for ALL. Studies on the relationship between High-Dose methotrexate (HD-MTX) toxicity and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C genes have drawn different conclusions. This study aimed to investigate the relationship between the polymorphism of MTHFR C677T and A1298C genes and the toxicity responses of MTX. Methods: The MTHFR C677T and A1298C genotypes of 271 children with ALL who received HD-MTX chemotherapy in southern China from September 2017 to June 2021 were analyzed, and the toxicity of HD-MTX was evaluated and analyzed according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0. Results: The MTHFR C677T and A1298C gene polymorphisms were not correlated with the 48-hour MTX blood concentrations (P>0.05). Unconditional logistic regression model analysis also revealed that the risk of liver function impairment [odds ratio (OR) =1.656, 95% confidence interval (CI): 1.179-2.324, P<0.05] and mucosal damage (OR =1.508, 95% CI: 1.042-2.183, P<0.05) were 1.656 and 1.508 times higher for the heterozygous mutant (CT), and homozygous mutant (TT) mutant type than for the wild-type (CC), wild-type, respectively. The risk of neutropenia and liver function impairment were 0.498 (OR =0.498, 95% CI: 0.251-0.989, P<0.05) and 6.067 (OR =6.067, 95% CI: 1.183-31.102, P<0.05) times higher in low-risk children with CT+TT mutant genotypes than in those with CC wild genotypes, respectively. Furthermore, the risk of mucosal damage was 1.906 times higher in high-risk children with the CT+TT genotype than in those with the CC genotype (OR =1.906, 95% CI: 1.033-3.518, P<0.05). The MTHFR A1298C genotypes differed in the incidence of liver function damage and gastrointestinal toxic reactions in children with ALL. Nonetheless, no increased risk of liver function impairment nor gastrointestinal reactions in children with the heterozygous mutant (AC)+CC mutation was observed. Conclusions: Advancements in MTHFR genotype testing in children with ALL and the introduction of personalised treatments based on genotype results during HD-MTX chemotherapy will help to predict, prevent, and reduce the occurrence of adverse MTX-related toxic reactions.

Systemic toxic effects of Mesocain® in routine surgical practice upon iatrogenic overdose requiring cardiopulmonary resuscitation - case report.

This case report of a patient with a traumatic head injury provides an example of a systemic toxic reaction to a local anesthetic. Clinical signs of a systemic toxic reaction and hemorrhagic shock may initially be similar: tachycardia, hypotension and unconsciousness. The purpose is thus to remind that even the treatment of a minor injury can develop into a life-threatening condition. When a skin wound is treated using suture under local or regional anesthesia, the annual incidence rate of systemic toxic reactions is 1:3,000 and that of death is 1:30,000.

Biocompatibility of bioprosthetic heart valve materials with a non-glutaraldehyde-based chemical treatment / 中国胸心血管外科临床杂志

@#Objective    To study the biocompatibility of bioprosthetic heart valve material with a non-glutaraldehyde-based treatment, and to provide the safety data for the clinical application. Methods    All the tests were conducted according to GB/T16886 standards. The in vitro cytotoxicity was determined by methyl thiazolyl tetrazolium assay. Fifteen guinea pigs were divided into a test group (n=10) and a control group (n=5) in the skin sensitization test. Three New Zealand white rabbits were used in the intradermal reactivity test. Five sites on both sides of the rabbit back were set as test sites and control sites, respectively. In the acute systemic toxicity test, a total of 20 ICR mice were randomly assigned to 4 groups: a test group (polar medium), a control group (polar medium), a test group (non-polar medium) and a control group (non-polar medium), 5 in each group. Forty SD rats were divided into a test group (n=20) and a control group (n=20) in the subchronic systemic toxicity test. Results    The viability of the 100% extracts of the bioprosthetic heart valve material with a non-glutaraldehyde-based treatment was 75.2%. The rate of positive reaction was 0.0%. The total intradermal reactivity test score was 0. There was no statistical difference in the body weight between the test group and control group in the acute systemic toxicity test. There was no statistical difference in the body weight, organ weight, organ weight/body weight ratio, blood routine test or blood biochemistry between the test group and control group in the subchronic systemic toxicity test. Conclusion    The bioprosthetic heart valve material with a non-glutaraldehyde-based treatment has satisfying biocompatibility, which conforms to relevant national standards. The material might be a promising material for application in valve replacement.

Effect of pemetrexed on the efficacy, toxic reaction, and survival rate of patients with EGFR-TKI resistant moderate and advanced lung cancer.

OBJECTIVE: To explore the effect of pemetrexed on the efficacy, toxic reaction, and survival rate of patients with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistant moderate to advanced lung cancer. METHODS: A total of 86 patients with EGFR-TKI resistant moderate and advanced lung cancer in our hospital were divided by therapeutic drugs into a control group (39 patients) and pemetrexed group (47 patients). Differences in general data, clinical efficacy, immunoglobulin expression, tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels, tumor markers, toxic reaction, and survival rate between the two groups were analyzed. RESULTS: Similar expression levels of carcinoembryonic antigen, IL-6, carbohydrate antigen 125, TNF-α, carbohydrate antigen 153 and immunoglobulin were found in the control group and pemetrexed group before treatment (all P>0.05). Expression levels of the above indicators in all patients decreased one month after the end of treatment, and levels of immunoglobulin, inflammatory factors, and tumor markers in the control group were higher than those in the pemetrexed group (all P<0.05). Similar incidence rates of toxic reactions were shown in the two groups (P>0.05). Twelve months after the end of treatment, one-year survival rate was significantly higher in the pemetrexed group than in the control group (χ2=3.332, P=0.042). CONCLUSION: Pemetrexed can significantly improve the clinical efficacy in patients with EGFR-TKI resistant lung cancer, decrease the expression of inflammatory factors, tumor markers, and immunoglobulin in serum, has few side effects on the body, and prolongs the long-term survival rate.

Sorafenib-associated hand-foot skin reaction: practical advice on diagnosis, mechanism, prevention, and management.

Introduction: Sorafenib is a multitargeted tyrosine kinase inhibitor, which has been mainly used in the treatment of advanced hepatocellular carcinoma and renal cancer. However, hand-foot skin reaction (HFSR), as one of the most common adverse reactions, have hindered its long-term clinical application. At present, the mechanism of its occurrence has not been clearly studied and it leads to the lack of effective means of intervention. This article reviews known mechanism and management methods of HFSR caused by sorafenib.Areas covered: The author reviews HFSR caused by the treatment of sorafenib including the mechanism and management. English language reports located through PubMed are reviewed.Expert opinion: There are some conjectures about the mechanism of HFSR. However, the mechanism of HFSR induced by sorafenib is still unclear at present. In the absence of understanding the mechanism of HFSR, the most common method for clinical treatment of sorafenib-induced HFSR is dose down-regulation or discontinuation of treatment, which affects efficacy and even survival. Future research should focus on the mechanism of HFSR to find out new ways for prevention. Precautionary measures before the occurrence of HFSR can also be studied in the future.

[Discussion on safety of Xanthii Fructus and consideration on its rational use].

Xanthii Fructus is a traditional Chinese medicine for the treatment of sinusitis and headache,rich in medicinal materials and is widely used for more than 1 800 years. Modern pharmacological studies have showed that Xanthii Fructus has anti-inflammatory,analgesic,anti-tumor,anti-bacterial,hypoglycemic,anti-allergic,immunomodulatory and other pharmacological effects,which can be commonly used in the treatment of diseases relating to immune abnormalities,such as rheumatoid arthritis,acute and chronic rhinitis,allergic rhinitis,and skin diseases,with a high medicinal value. Toxicological studies have shown that Xanthii Fructus poisoning can cause substantial damage to organs,such as the liver,kidney,and gastrointestinal tract,especially to liver. Because of the coexisting of its efficacy and toxicity,Xanthii Fructus often leads to a series of safety problems in the clinical application process. This study attempts to summarize its characteristics of adverse reactions,analyze the root cause of the toxicity of Xanthii Fructus from such aspects as processing,dose,course of treatment and eating by mistake,discuss the substance of its efficacy/toxicity from chemical compositions,and put forward exploratory thinking about how to promote its clinical rational application from the aspects such as strict processing,reasonable compatibility,medication information,contraindication,strict control of the dose,and course of treatment,so as to promote the safe and reasonable application of Xanthii Fructus.

Discussion on safety of Xanthii Fructus and consideration on its rational use / 中国中药杂志

Xanthii Fructus is a traditional Chinese medicine for the treatment of sinusitis and headache,rich in medicinal materials and is widely used for more than 1 800 years. Modern pharmacological studies have showed that Xanthii Fructus has anti-inflammatory,analgesic,anti-tumor,anti-bacterial,hypoglycemic,anti-allergic,immunomodulatory and other pharmacological effects,which can be commonly used in the treatment of diseases relating to immune abnormalities,such as rheumatoid arthritis,acute and chronic rhinitis,allergic rhinitis,and skin diseases,with a high medicinal value. Toxicological studies have shown that Xanthii Fructus poisoning can cause substantial damage to organs,such as the liver,kidney,and gastrointestinal tract,especially to liver. Because of the coexisting of its efficacy and toxicity,Xanthii Fructus often leads to a series of safety problems in the clinical application process. This study attempts to summarize its characteristics of adverse reactions,analyze the root cause of the toxicity of Xanthii Fructus from such aspects as processing,dose,course of treatment and eating by mistake,discuss the substance of its efficacy/toxicity from chemical compositions,and put forward exploratory thinking about how to promote its clinical rational application from the aspects such as strict processing,reasonable compatibility,medication information,contraindication,strict control of the dose,and course of treatment,so as to promote the safe and reasonable application of Xanthii Fructus.

Discussion and consideration on safety of Sophorae Tonkinensis Radix et Rhizoma and its rational use / 中草药

Sophorae Tonkinensis Radix et Rhizoma is known as the important drug for treating sore throat and is widely used in clinic. Because of the coexisting of its efficacy and poison, Sophorae Tonkinensis Radix et Rhizoma often leads to a series of safety problems in the clinical application process. In this study, we attempt to analyze the ultimate cause of the toxicity of Sophorae Tonkinensis Radix et Rhizoma by reviewing nearly 20 years of literature, discuss the substance of its efficacy/toxicity from the point of view of chemical composition, and put forward exploratory thinking on its clinical rational application.

Observation of Fluorouracil Implants on the Intraperitoneal Chemotherapy Safety of Advanced Gastric Cancer Patients / 中国药房

OBJECTIVE:To investigate the effects of Fluorouracil implants on intraperitoneal chemotherapy safety of advanced gastric cancer patients. METHODS:The information of 264 patients with advanced gastric cancer were analyzed retrospectively. All patients were given Fluorouracil implants 800 mg,scattered into the mesenteric and surgical area,dose of each implantation site less than 200 mg,the distance of implantation range from incision and anastomosis more than 3 cm. All patients were given second generation cephalosporin 30 min before operation,at 3rd h during operation,1-3 d after operation. The occurrence of complications and ADR during hospitalization were observed after operation. RESULTS:After operation,6 patients suffered from complications, with incidence of 2.28%,including 3 cases of gastrointestinal reaction,2 cases of anastomotic bleeding and 1 case of anastomotic leakage. Routine blood test and liver and kidney function were rechecked 3 d after operation,mainly thrombocytopenia and liver function injury,with the incidence of 2.65%. CONCLUSIONS:Fluorouracil implants can be used for intraperitoneal chemotherapy of advanced gastric cancer patients. However,attention should be paid to thrombocytopenia and liver function injury.

Genetic polymorphisms of Wnt/ß-catenin pathway genes are associated with the efficacy and toxicities of radiotherapy in patients with nasopharyngeal carcinoma.

Radiotherapy (RT) is the normative therapeutic treatment for primary nasopharyngeal carcinoma (NPC). Single nucleotide polymorphisms (SNPs) of genes in Wnt/ß-catenin pathway are correlated to the development, prognosis, and treatment benefit of various cancers. However, it has not been established whether SNPs of Wnt/ß-catenin pathway are associated with nasopharyngeal tumorigenesis and the efficacy of RT in NPC patients. Therefore, in this study, we aimed to investigate the nine potentially functional SNPs of four genes in the Wnt/ß-catenin pathway and genotyped these in 188 NPC patients treated with RT. To achieve this goal, associations between these SNPs and the RT's curative efficacy, as well as acute radiation-induced toxic reaction were determined by multifactorial logistic regression. We observed that catenin beta 1 gene (CTNNB1) rs1880481 and rs3864004, and glycogen synthase kinase 3 beta gene (GSK3ß) rs3755557 polymorphisms were significantly associated with poorer efficacy of RT in NPC patients. Moreover, GSK3ß rs375557 and adenomatous polyposis coli gene (APC) rs454886 polymorphisms were correlated with acute grade 3-4 radiation-induced dermatitis and oral mucositis, respectively. In conclusion, this study suggests that gene polymorphisms of Wnt/ß-catenin may be novel prognostic factors for NPC patients treated with RT.

Clinical Observation of Tegafur Gimeracil Oteracil Potassium Combined with 3D-CRT and Microwave Hy-perthermia in the Treatment of Elderly Patients with Local Advance Esophageal Cancer / 中国药房

OBJECTIVE:To observe clinical efficacy and safety of tegafur gimeracil oteracil potassium combined with 3D-CRT and microwave hyperthermia in the treatment of elderly patients with local advance esophageal cancer. METHODS:48 cases of local advance esophageal cancer were divided into group A,B and C according to random number table method,with 16 cases in each group according to random number table method. Group A was given 3D-CRT with total dose of 60-66 Gy totnlly for 6-7 weeks;group B was additionally given tegafur gimeracil oteracil potassium 60 mg/(m2·d),bid,on the basis of group A 3 weeks for a course of treatment,until the end of radvotherapy;group C was additionally given thermotherapy on the basis of group B 3 weeks for a course of treatment,until the end of radvotherapy. Clinical efficacy,1-year survival rate,dysphagia,weight and KPS score were compared among 3 groups,and the occurrence of toxic reactions(radioactive esophagitis,radioactive pneumonia, bone marrow suppression and gastrointestinal reaction) were observed in 3 groups. RESULTS:Total effective rate,1-year survival rate and the remission rate of dysphagia of group C were 93.75%,87.50% and 93.75%,which were significantly higher than those of group A(50.00%,50.00% and 56.25%)and B(68.75%,68.75% and 68.75%),with statistical significance(P0.05). The incidence of radioactive esophagitis and radioactive pneumonia in group C were significantly lower than in group A and B,with statistical significance(P0.05). CONCLUSIONS:Tegafur gimeracil oteracil potassium combined with 3D-CRT and microwave hyperthermia in the treat-ment of elderly patients with local advance esophageal cancer further improves clinical efficacy and survival rate,but shows low inci-dence of toxic reaction.

Impact of the dual defence system of Plantago lanceolata (Plantaginaceae) on performance, nutrient utilisation and feeding choice behaviour of Amata mogadorensis larvae (Lepidoptera, Erebidae).

Iridoid glycosides are plant defence compounds with potentially detrimental effects on non-adapted herbivores. Some plant species possess ß-glucosidases that hydrolyse iridoid glycosides and thereby release protein-denaturing aglycones. To test the hypothesis that iridoid glycosides and plant ß-glucosidases form a dual defence system, we used Plantago lanceolata and a polyphagous caterpillar species. To analyse the impact of leaf-age dependent differences in iridoid glycoside concentrations and ß-glucosidase activities on insect performance, old or young leaves were freeze-dried and incorporated into artificial diets or were provided freshly to the larvae. We determined larval consumption rates and the amounts of assimilated nitrogen. Furthermore, we quantified ß-glucosidase activities in artificial diets and fresh leaves and the amount of iridoid glycosides that larvae feeding on fresh leaves ingested and excreted. Compared to fresh leaves, caterpillars grew faster on artificial diets, on which larval weight gain correlated positively to the absorbed amount of nitrogen. When feeding fresh young leaves, larvae even lost weight and excreted only minute proportions of the ingested iridoid glycosides intact with the faeces, indicating that the hydrolysis of these compounds might have interfered with nitrogen assimilation and impaired larval growth. To disentangle physiological effects from deterrent effects of iridoid glycosides, we performed dual choice feeding assays. Young leaves, their methanolic extracts and pure catalpol reduced larval feeding in comparison to the respective controls, while aucubin had no effect on larval consumption. We conclude that the dual defence system of P. lanceolata consisting of iridoid glycosides and ß-glucosidases interferes with the nutrient utilisation via the hydrolysis of iridoid glycosides and also mediates larval feeding behaviour in a concentration- and substance-specific manner.

Accidental contamination of a German town's drinking water with sodium hydroxide.

Case report of a very serious drinking water incident putting up to 50,000 inhabitants of a town near Bonn in North Rhine-Westphalia, Germany at risk. A concentrated solution of highly alkaline water by sodium hydroxide was accidentally washed into the town's drinking water at a pumping station and increased the pH-value of the water to 12. Residents who came into contact with the contaminated water immediately had a toxic reaction. The incident was detected by complaints from customers and after that was stopped within several hours. The pipes were flushed and the customers were warned not to use the water till the all clear. After this immediate management there was an investigation and the cause of the incident was detected as an accidental release of accumulated sodium hydroxide (NaOH) solution. The lack of a network alarm system and the automatic cut-off mechanisms as deficiencies in the design of the station were rectified by the water company immediately after the incident.

Relationship Between Serum Concentration at 48 h and Pharmacokinetic Characteristics and Toxic Reactions at Terminal Elimination Phase After Starting High Dose Methotrexate Infusion / 医药导报

Objective To recheck the reliability of methotrexate ( MTX) serum concentration at 48 h ( C48 h ) in predicting the pharmacokinetic characteristics and toxic reactions at terminal elimination phase after high dose MTX infusion and to provide a reference for determination of rational rescue regimen in clinic practice. Methods In total,114 cases of children with acute lymphoblastic leukemia (ALL) received 176 courses of high dose MTX chemotherapy treatment. The regimen was continuous infusion of MTX[3 -5 g·( m2 ) -1 ] in 24 h. Plasma samples were treated with solid phase extraction and serum concentrations of MTX were determined by HPLC at 24,48 and 72 h (C24 h ,C48 h and C72 h ) after starting MTX infusion. All data were divided into C48 h≥1 μmol·L-1 group and C48 h<1 μmol·L-1 group. The pharmacokinetic parameters of the two groups at elimination phase were estimated by residual method and the toxic reactions after MTX infusion of two groups were compared by Ridit analysis. Results The C72 h and AUC48-∞ were significantly higher in C48 h ≥1 μmol · L-1 group than in C48 h <1 μmol·L-1 group (P<0. 01). The MTX toxicities to the blood,digestive and hepatic systems were significantly higher in C48 h≥1 μmol·L-1 group than in C48 h < 1 μmol · L-1 group ( P < 0. 05). Conclusion C48 h can predict the pharmacokinetic characteristics and toxic reactions at ther terminal elimination phase. Therefore,C48 h≥1 μmol·L-1 can be used as a marker of MTX elimination delay event to guide later rescue regimen.

Pneumococcal Vaccination-Induced Localized Cutaneous Toxic Reaction Mimicking Fixed Drug Eruption on a Nearby Vaccination Injection Site in an Infant / 대한피부과학회지

Pneumococcus is a very important pathogen for children and elderly people, and causes considerable morbidity and mortality in these groups. Pneumococcal vaccination is relatively safe, and is being increasingly used for the prevention of pneumococcal disease, such as meningitis, pneumonia, otitis media, and bacteremia. Mild adverse reactions of pneumococcal vaccination are relatively common, and include erythema, pain, fever, myalgia, and headaches. However, adverse skin reactions are very rare. Here, we present a case of pneumococcal vaccination-induced localized toxic reaction mimicking fixed drug eruption on a nearby vaccination injection site in an infant, which has not previously been documented in Korea.

Clinical Observation of Shen-fu Injection on Toxic Reaction Relief in the Chemotherapy for Moderate to Advanced NSCLC / 中国药房

OBJECTIVE:To investigate the effect of shen-fu injection on toxic reaction relief in the chemotherapy for moderate to advanced non-small cell lung cancer(NSCLC).METHODS:130 patients of NSCLC were randomly divided into treatment group and control group,2 groups both received the second-generation regimen for chemotherapy,the major chemotherapeutic agents included vinorelbine,gemcitabine and paclitaxel,the treatment group was given intravenous shen-fu injection 60ml/d for continuous2weeks plus chemotherapy.RESULTS:The toxic reactions in treatment group significantly decreased compared to that in the control group(P

The toxic reactions of all-trans retinoic acid occuring in the treatment of acute promyelocytic leukemia / 中国癌症杂志

Purpose:To observe the toxic reactions of all trans retinoic acid in the treatment of acute promyelocytic leukemia. Methods:Analysis of toxic reaction was done for 38 patients who suffered from acute promyelocytic leukemia treated with all trans retinoic acid. Results:In the treatment of acute promyelocytic leukemia with all trans retinoic acid, the common toxic reactios are dry mouth, skin desiccation, desquamation, rhagadia (100%). 19 patients had gastro intestinal symptoms with higher ALT(50%),18 patients had hyperleukocytosis syndrome (47.5%), 16 patients had headache and dizziness (42.4%),8 patients had pain in muscle and joint (21.2%). The rare toxic reactions included 4/38 who had intracranial hypertension syndrome, 2/38 had hyperglycemia, 1/38 and hyperhistaminemia syndrome. Conclusions:The toxic reactions of all trans retinoic acid in the treatment of acute promyelocytic leukemia usually have dry mouth ,skin desiccation, desquamation, rhagadia, gastro intestine symptom with higher ALT, and hyperleukocytosis syndrome ets. THe treatment with lower dose of all trans retinoic acid(20～30 mg/d)for acute promyelocytic leukemia could decrease the toxic reactions without influencing its effectiveness.