Causes of Death during the Intravenous Infusion of Dimethylsulphoxide and Hydrogen Peroxide in the Course of Alternative Medicine Therapy.

Unconventional (alternative, natural) medicine in Poland and worldwide includes hundreds of non-scientifically verified "treatment" modalities. Among the most popular are biological therapies using chemical or natural compounds administered with injection or drip infusion. The latter has found the most excellent use in treating rheumatological and dermatological diseases and certain types of cancer. Vitamin infusions, curcumin, glutathione, perhydrol and dimethylsulphoxide (DMSO) have gained popularity among clients of natural medicine clinics. The present study aims to analyse the case of a 37-year-old woman who was administered infusions containing perhydrol and DMSO (0.5 mL 0.04% hydrogen peroxide/0.5 mL p.d.a DMSO in saline) due to a MTHFR A1298C mutation. After having the next infusion, the woman complained of nausea and then became unconscious. Subsequently, she suffered respiratory and cardiac arrest. Adequate resuscitation was undertaken. After being taken to the hospital, the patient was in critical condition and died due to increasing multiple-organ failure. Initially, there was suspected DMSO poisoning as it was the only compound to have been administered as an intravenous infusion. However, it was not until the analysis of the secured evidence that it became clear that the patient had also been given an intravenous solution of hydrogen peroxide, H2O2, and that there had been a mistake in preparing the intravenous perhydrol solution. The autopsy concluded that the immediate cause of death was an acute cardiopulmonary failure due to the toxic effects of intravenously administered hydrogen peroxide. This conclusion was established after the toxicological testing of the evidence and biological material secured during the patient's treatment and autopsy. Products containing DMSO and perhydrol are not included in the lists of medicinal/therapeutical forms and preparations and thus are not authorised for marketing in Poland. In the case of perhydrol, apart from the topical use of diluted preparations for washing and cleansing wounds, no data on therapeutic use exist in the available scientific literature. Furthermore, "DMSO and perhydrol therapy" cannot even be considered a placebo effect, as both are toxic compounds which could, at most, cause poisoning symptoms rather than improve health.

Characteristics of E-Scooter-Related Maxillofacial Injuries over 2019-2022-Retrospective Study from Poznan, Poland.

Recently, there has been a considerable rise in the popularity and use of electric scooters. Because of this, the number of accidents involving them has also risen. Head and neck injuries are the most common. The aim of the study was to determine the most frequent craniofacial injuries resulting from accidents involving electric scooters, and to identify the risk factors directly related to their placement and severity. The study carried out a retrospective analysis of the medical records of patients of the Clinic of Maxillofacial Surgery over 2019-2022, in terms of craniofacial injuries suffered as a result of e-scooter-related accidents. In the study population (31 cases), of which 61.3% were men, the median age was 27 years. At the time of the accident, 32.3% patients were under the influence of alcohol. Accidents were most common in the 21-30 age group; more often than not, they occurred during warm months and on weekends. The study identified a total of 40 fractures in the patients. The most common craniofacial injuries were mandibular fractures (37.5%), zygomatic-orbital fractures (20%) and frontal bone fractures (10%). A multidimensional correspondence analysis was also performed, which showed that at an age of under 30, alcohol consumption and female gender were associated with a higher likelihood of mandibular fracture. Proper education on the risks associated with the use of e-scooters is essential, with particular emphasis on the impact of alcohol on the driver. It is important to develop diagnostic and therapeutic algorithms for doctors, both in ED and in specialised departments.

PELP1 and SRC kinase as important molecules in the estrogen-mediated pathway in human testis and epididymis.

BACKGROUND: Estrogens have pleiotropic mechanisms of action, and their cellular transduction pathways can modulate various proteins with differential tissue expression. Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is one such protein whose role seems important, although little is known about this protein. However, very little is known about the expression of modulators involved in the estrogen-mediated pathways in the tissues of the male reproductive tract. METHODS: In this study, we obtained autopsy specimens of testis and epididymis from 13 men of Caucasian descent. Expression levels were analyzed for both estrogen receptors (ESR1 and ESR2) and their co-regulators, including PELP1 and kinase c-Src (SRC). RESULTS: Protein expression was confirmed with western blot and immunocytochemistry techniques. The expression of both SRC and PELP1 was significantly higher in the testis compared to the epididymis (p=0.040 and p=0.002, respectively). Furthermore, a significant, positive correlation was observed between SRC and PELP1, regardless of tissue type p<0.0001, R=0.78). In the testis, PELP1 expression positively correlated with ESR1 expression (p=0.367, R=0.6). CONCLUSIONS: Our study suggests a possible relationship between PELP1, SRC, and ESR1 in the human testis and epididymis. This study makes a valuable contribution to the field of estrogen-mediated pathways in the male reproductive tract and describes trends of analyzed genes' expression and presence. We think our results may open some new research directions of the estrogen signaling in the male reproductive system.

[Diagnostic difficulties and legal analysis of potential claims to occupational medicine specialists based on a case of unrecognizable cardiac angiosarcoma]. / Trudnosci diagnostyczne i analiza prawna potencjalnych roszczen wobec lekarza medycyny pracy na przykladzie nierozpoznanego naczyniakomiesaka serca.

The article presents a case of sudden death of a 56-year-old woman at the workplace, caused by a very rare primary cardiac tumor. The patient's family reported a crime to the prosecutor's office suggesting participation of third parties in causing the death or malpractice in physical examinations before the death. A review of clinical data concerning cardiac angiosarcoma, available in electronic databases (e.g., Web of Science, PubMed), was presented, which could be useful in the practice of occupational medicine specialists. A legal analysis of potential claims to occupational medicine specialist in the case of failure to recognize primary cardiac tumors was also included in the article. Med Pr. 2020;71(6):757-64.

Determination of prodrug treosulfan and its biologically active monoepoxide in rat plasma, liver, lungs, kidneys, muscle, and brain by HPLC-ESI-MS/MS method.

A prodrug treosulfan (TREO) is currently investigated in clinical trials for conditioning prior to hematopoietic stem cell transplantation. Bioanalysis of TREO and its active derivatives, monoepoxide (S,S-EBDM) and diepoxide, in plasma and urine underlay the pharmacokinetic studies of these compounds but cannot explain an organ pharmacological action or toxicity. Recently, distribution of TREO and S,S-EBDM into brain, cerebrospinal fluid, and aqueous humor of the eye has been investigated in animal models and the obtained results presented clinical relevance. In this paper, a selective and rapid HPLC-ESI-MS/MS method was elaborated and validated for the studies of disposition of TREO and S,S-EBDM in rat plasma, liver, lungs, kidneys, muscle, and brain. The two analytes and codeine, internal standard (IS), were isolated from 50µL of plasma and 100µL of supernatants of the tissues homogenates using ultrafiltration Amicon vials. Chromatographic resolution was accomplished on C18 column with isocratic elution. The limits of quantitation of TREO and S,S-EBDM in the studied matrices ranged from 0.11 to 0.93µM. The HPLC-MS/MS method was adequately precise and accurate within and between runs. The IS-normalized matrix effect differed among the tissues and was the most pronounced in a liver homogenate supernatant (approximately 0.55 for TREO and 0.35 for S,S-EBDM). Stability of the analytes in experimental samples was also established. The validated method for the first time enabled determination of TREO and S,S-EBDM in the six life-important tissues in rats following administration of the prodrug.

Pharmacokinetics of treosulfan and its active monoepoxide in pediatric patients after intravenous infusion of high-dose treosulfan prior to HSCT.

Pro-drug treosulfan (TREO) is currently evaluated in randomized phase III clinical trials as a conditioning agent prior to HSCT. In the present paper pharmacokinetics of both TREO and its biologically active monoepoxide (S,S-EBDM) was investigated in pediatric patients for the first time. The studies were carried out in 16 children (median age 7.5 years) undergoing TREO-based preparative regimen prior to HSCT, who received 10, 12 or 14 g/m(2) of the drug as a 1h or 2h intravenous infusion. Plasma concentrations of TREO as well as S,S-EBDM were determined using the validated HPLC-MS/MS method. The changes in S,S-EBDM concentration over time followed TREO levels. The area under the curve (AUC) of TREO was 100-fold higher than AUC of S,S-EBDM. No statistically significant dependency of the dose-normalized AUC of either TREO or S,S-EBDM on the patients' age and body surface area was stated. Moreover, plasma C(max) as well as AUC of S,S-EBDM demonstrated linear correlation with the C(max) and AUC of TREO, respectively. The biological half-lives of TREO and S,S-EBDM were similar. This indicates that S,S-EBDM was completely eliminated from the patients' blood within relatively short time, comparable to TREO.

Direct high-performance liquid chromatography method with refractometric detection designed for stability studies of treosulfan and its biologically active epoxy-transformers.

Treosulfan (TREO) is an alkylating agent registered for treatment of advanced platin-resistant ovarian carcinoma. Nowadays, TREO is increasingly applied iv in high doses as a promising myeloablative agent with low organ toxicity in children. Under physiological conditions it undergoes pH-dependent transformation into epoxy-transformers (S,S-EBDM and S,S-DEB). The mechanism of this reaction is generally known, but not its kinetic details. In order to investigate kinetics of TREO transformation, HPLC method with refractometric detection for simultaneous determination of the three analytes in one analytical run has been developed for the first time. The samples containing TREO, S,S-EBDM, S,S-DEB and acetaminophen (internal standard) were directly injected onto the reversed phase column. To assure stability of the analytes and obtain their complete resolution, mobile phase composed of acetate buffer pH 4.5 and acetonitrile was applied. The linear range of the calibration curves of TREO, S,S-EBDM and S,S-DEB spanned concentrations of 20-6000, 34-8600 and 50-6000 µM, respectively. Intra- and interday precision and accuracy of the developed method fulfilled analytical criteria. The stability of the analytes in experimental samples was also established. The validated HPLC method was successfully applied to the investigation of the kinetics of TREO activation to S,S-EBDM and S,S-DEB. At pH 7.4 and 37 °C the transformation of TREO followed first-order kinetics with a half-life 1.5h.

HPLC method for determination of biologically active epoxy-transformers of treosulfan in human plasma: pharmacokinetic application.

Clinical trials demonstrated treosulfan (TREO) as a promising myeloablative agent prior to hematopoietic stem cell transplantation (HSCT). TREO is a specific pro-drug from which biologically active mono- (S,S-EBDM) and diepoxybutane (S,S-DEB) derivatives are formed in vitro or in vivo by a non-enzymatic pH and temperature-dependent intramolecular nucleophilic substitution. Following extraction of the plasma samples with a mixture of dichloromethane and acetonitrile, S,S-EBDM and S,S-DEB were derivatized with 3-nitrobenzenesulfonic acid (3-NBS) to UV-absorbing esters. Optimal temperature and time of derivatization as well as extraction method and also the effect of pH on TREO stability in plasma were established. Identity of the synthesized derivatives was confirmed by mass spectrometry. The post-derivatization mixture was purified from the excess of unreacted 3-NBS by extraction with water. The derivatization products and 2,2'-dinitrobiphenyl (internal standard) were separated on Nucleosil 100 C18 column using a mobile phase consisted of acetonitrile and water. The developed method was validated and demonstrated adequate accuracy and precision. Limit of quantification for both S,S-EBDM and S,S-DEB amounted to 2.5 µM. The method was applied in clinical conditions to quantify the levels of TREO activation products in plasma of children undergoing HSCT. The methodology for simultaneous determination of TREO epoxy-transformers in human plasma is described for the first time.

Acute collective gas poisoning at work in a manure storage tank.

Cases of deaths in manure or septic tanks are rare in legal-medical practice, more frequently as unfortunate occupational accidents. Poisoning with toxic gases, especially with hydrogen sulfide, is reported as the cause of death, while the exhaustion of oxygen in the air is omitted with the simultaneous excess of carbon dioxide. In such cases, determination of the direct cause of death constitutes a big problem because post-mortem examination does not reveal the specific changes. A case of acute collective poisoning by gases in a manure storage tank is presented of 5 agricultural workers, 2 of whom died. While explaining the cause of poisoning and deaths, toxicological blood tests were performed in the victims of the accident, as well as gases inside the manure storage tank. The post-mortem examinations and toxicological blood tests performed did not allow determination of the direct cause of death. Toxicological tests of gases from inside the manure tank showed a very low concentration of oxygen, with a simultaneous very high concentration of carbon dioxide, and a considerable level of hydrogen sulfide. The cause of fainting of three and deaths of two workers was not the poisoning with hydrogen sulfide, but oxygen deficiency in the air of the tank.

Fournier's gangrene: historical survey, current status, and case description.

BACKGROUND: The first-documented clinical picture of the disease was made by Fournier in 1883. Its epidemiology has changed and is much different from the original. It is infectious in its etiology, affecting mostly men between 50 and 60 years of age. Predisposing factors include diabetes, neoplasms, chronic glucocorticoid therapy, immune-compromise, chemo- and radiotherapy, immunosuppression, Crohn's disease, and alcohol abuse. High mortality results from the rapid progress of the disease, leading to quick development of septic shock and multi-organ failure. Most important in the treatment of Fournier's gangrene are surgical debridement of the wound, fascia incision and drainage of necrotic lesion, and intravenous antibiotic therapy. The typical picture of the disease might be hidden by concomitant disease. CASE REPORT: A case of Fournier's gangrene in an 81-year-old woman with concomitant neurologic complications, hypertension, cardiomyopathy, and chronic obstructed pulmonary disease is described. Three days after the suspected diagnosis, the decision was made to fully remove the necrotic tissue surgically. Despite all the efforts of the medical team, the patient died 14 days after being diagnosed with Fournier gangrene. The immediate cause of death was septic shock. CONCLUSIONS: In the early stages of the disease, before necrotic lesions occur, a final diagnosis might be difficult. In the present case, death was caused by the patient's advanced age, simultaneously appearing symptoms, and late surgical intervention, but mostly by lung failure.

[Medico-legal problems of providing first aid]. / Prawno-medyczne problemy udzielania pierwszej pomocy.

The paper presents medico-legal problems associated with providing assistance to victims of traffic accidents. Legal acts have been analyzed in the aspect of help provision. Inconsistencies, and even divergences between individual regulations of the legal acts have been demonstrated. Particular attention has been paid to circumstances of providing emergency assistance, its scope, and situations when the obligation of providing first aid is no longer binding. The problem of provision or refusal to provide help seems--according to the authors--to be valid, since not all relevant legal regulations are generally known.