Retinoic acid inhibits histone methyltransferase Whsc1 during palatogenesis.

Cleft lip with or without palate (CL/P) is a common congenital anomaly in humans and is thought to be caused by genetic and environmental factors. However, the epigenetic mechanisms underlying orofacial clefts are not fully understood. Here, we investigate how the overdose of retinoic acid (RA), which can induce cleft palate in mice and humans, regulates histone methyltransferase, Wolf-Hirschhorn syndrome candidate 1 (WHSC1) during palatal development in mice. We treated mouse embryonic fibroblasts (MEFs) with 1 µM all-trans RA and discovered that the global level of H3K36me3 was downregulated and that expression of the H3K36 methyltransferase gene, Whsc1, was reduced. The expression level of WHSC1 in embryonic palatal shelves was reduced during palatogenesis, following maternal administration of 100 mg/kg body weight of RA by gastric intubation. Furthermore, the expression of WHSC1 in palatal shelves was observed in epithelial and mesenchymal cells at all stages, suggesting an important role for palatal development. Our results suggest that the pathogenesis of cleft palate observed after excessive RA exposure is likely to be associated with a reduction in the histone methyltransferase, WHSC1.

[Myocardial infarction in the course of ethylene glycol poisoning--a case report]. / Zawal serca w przebiegu zatrucia glikolem etylenowym--opis przypadku.

The following paper describes the case of the 59-year-old patient moved from Clinical Cardiology to the Centre of Clinical Toxicology because of severe ethylene glycol poisoning, which occurred in the course of myocardial infarction of inferior wall. Ethylene glycol concentration was 85 mg/dl, the blood pH - 6.9, troponin >50 ng/ml, CK-MB 297.1 U/L. ECG current of injury was found at the bottom of the wall cuts reflective reductions in section ST in leads I, aVL and the precordial leads. In the coronarography was RCA occlusion, OM critical stenosis and suspected mouth of LAD stenosis. RCA urgent angioplasty was performed with implantation of bare metal stents 5. In addition, toxicological treatment consisted of mechanical ventilation, hemodialysis, ethanol, and intensive medical care. On 19 day of hospitalization the patient in good general condition was discharged home.

Unusual Presentation of Kratom Overdose With Rhabdomyolysis, Transient Hearing Loss, and Heart Failure.

Kratom mainly grows in Southeast Asia. It is widely used for pain management and opioid withdrawal, which is available online for cheaper prices. Alkaloids extracted from kratom such as mitragynine and 7-hydroxy mitragynine exhibit analgesic properties by acting through µ receptors. Commonly reported side effects of kratom include hypertension, tachycardia, agitation, dry mouth, hallucinations, cognitive and behavioral impairment, cardiotoxicity, renal failure, cholestasis, seizures, respiratory depression, coma, and sudden cardiac death from cardiac arrest. Rhabdomyolysis is a less commonly reported lethal effect of kratom. Limited information is available in the literature. In this article, we present a case of a 45-year-old female who is overdosed with kratom and presented with lethargy, confusion, transient hearing loss, and right lower extremity swelling and pain associated with weakness who was found to have elevated creatinine phosphokinase. She was diagnosed with rhabdomyolysis, compartment syndrome, multiorgan dysfunction including acute kidney injury, liver dysfunction, and cardiomyopathy. She underwent emergent fasciotomy and required hemodialysis. Her renal and liver function subsequently improved. We described the case and discussed pharmacology and adverse effects of kratom toxicity with a proposed mechanism and management. We conclude that it is essential for emergency physicians, internists, intensivists, cardiologists, and nephrologists to be aware of these rare manifestations of kratom and consider a multidisciplinary approach.

Acute fluvoxamine poisoning.

A total of 221 cases of deliberate acute overdose with fluvoxamine reported to the Paris Poison Centre, and 78 cases collected by the International Drug Safety Department of Duphar BV were analysed. Other agents, mainly benzodiazepines, neuroleptics, other antidepressants and alcohol, were also taken in 77% of the cases. The acute toxicity that could be attributed to fluvoxamine alone was rarely severe. The symptoms observed were always benign when the dose of fluvoxamine was below 1000 mg and included drowsiness, tremor, nausea, vomiting, abdominal pain, bradycardia and/or anticholinergic effects (dry mouth, mydriasis, sinus tachycardia, urinary retention). Seizures occurred in a few cases after high doses (generally > 1500 mg). Cardiotoxicity was not a serious problem; sinus bradycardia was noted with doses of less than 1000 mg, but was always moderate and required no treatment. Conduction abnormalities were rare.

Oral mucositis in patients receiving low-dose methotrexate therapy for rheumatoid arthritis: report of 2 cases and literature review.

BACKGROUND: The differential diagnosis of ulcerative oral lesions is diverse. This report discusses the rare causes of oral mucosal ulceration and suggests approaches for diagnosis and treatment. METHODS: Two cases of methotrexate-induced stomatitis in patients receiving low dose methotrexate for rheumatoid arthritis are presented with a review of the current literature. In case 1, mucositis was caused by an unintended methotrexate overdose. In case 2, oral lesions were the result of chronic methotrexate toxicity. The treatment for methotrexate-induced mucositis required hospitalization in case 1, methotrexate discontinuation in both cases and oral folic acid supplementation in case 2. RESULTS: In both cases, the mucositis healed and no relapse was observed. CONCLUSION: Mucositis may be an early sign of systemic conditions, and dental providers are often the first doctors involved in the assessment of oral mucosal diseases. Meticulous questioning of the patient's history and the physical examination is important for elucidating the underlying cause.

Adverse sedation events in pediatrics: analysis of medications used for sedation.

OBJECTIVES: To perform a systematic investigation of medications associated with adverse sedation events in pediatric patients using critical incident analysis of case reports. METHODS: One hundred eighteen case reports from the adverse drug reporting system of the Food and Drug Administration, the US Pharmacopoeia, and the results of a survey of pediatric specialists were used. Outcome measures were death, permanent neurologic injury, prolonged hospitalization without injury, and no harm. The overall results of the critical incident analysis are reported elsewhere. The current investigation specifically examined the relationship between outcome and medications: individual and classes of drugs, routes of administration, drug combinations and interactions, medication errors and overdoses, patterns of drug use, practitioners, and venues of sedation. RESULTS: Ninety-five incidents fulfilled study criteria and all 4 reviewers agreed on causation; 60 resulted in death or permanent neurologic injury. Review of adverse sedation events indicated that there was no relationship between outcome and drug class (opioids; benzodiazepines; barbiturates; sedatives; antihistamines; and local, intravenous, or inhalation anesthetics) or route of administration (oral, rectal, nasal, intramuscular, intravenous, local infiltration, and inhalation). Negative outcomes (death and permanent neurologic injury) were often associated with drug overdose (n = 28). Some drug overdoses were attributable to prescription/transcription errors, although none of 39 overdoses in 34 patients seemed to be a decimal point error. Negative outcomes were also associated with drug combinations and interactions. The use of 3 or more sedating medications compared with 1 or 2 medications was strongly associated with adverse outcomes (18/20 vs 7/70). Nitrous oxide in combination with any other class of sedating medication was frequently associated with adverse outcomes (9/10). Dental specialists had the greatest frequency of negative outcomes associated with the use of 3 or more sedating medications. Adverse events occurred despite drugs being administered within acceptable dosing limits. Negative outcomes were also associated with drugs administered by nonmedically trained personnel and drugs administered at home. Some injuries occurred on the way to a facility after administration of sedatives at home; some took place in automobiles or at home after discharge from medical supervision. Deaths and injuries after discharge from medical supervision were associated with the use of medications with long half-lives (chloral hydrate, pentobarbital, promazine, promethazine, and chlorpromazine). CONCLUSIONS: Adverse sedation events were frequently associated with drug overdoses and drug interactions, particularly when 3 or more drugs were used. Adverse outcome was associated with all routes of drug administration and all classes of medication, even those (such as chloral hydrate) thought to have minimal effect on respiration. Patients receiving medications with long plasma half-lives may benefit from a prolonged period of postsedation observation. Adverse events occurred when sedative medications were administered outside the safety net of medical supervision. Uniform monitoring and training standards should be instituted regardless of the subspecialty or venue of practice. Standards of care, scope of practice, resource management, and reimbursement for sedation should be based on the depth of sedation achieved (ie, the degree of vigilance and resuscitation skills required) rather than on the drug class, route of drug administration, practitioner, or venue.

Hemodiafiltration for vancomycin overdose in a patient with end-stage renal failure.

A 17-year-old anuric female patient with end-stage renal failure received a massive overdose of vancomycin and was treated with high-flux hemodiafiltration, as described in this report. The hemodiafiltration procedure with a polysulfone membrane was performed 3 times. The vancomycin concentration was decreased from 101 mg/l to 16.59 mg/l at the end of the procedure. No adverse effects were noted from either vancomycin or hemodiafiltration. Hemodiafiltration with a high-flux polysulfone membrane is a novel and safe treatment modality for vancomycin overdose in pediatric patients.