Determination of drug levels in larvae of Lucilia sericata (Diptera: Calliphoridae) reared on rabbit carcasses containing morphine

This study concerns the determination of morphine concentrations in fly larvae reared on rabbits administered different concentrations of morphine and a correlation between concentrations of the drug in larvae and tissues. Three rabbits (R1, R2 and R3) were given dosages of 12.5, 25.0 and 50.0 mg/h of morphine over a 3 h period via continuous ear artery perfusion. These dosages and time of perfusion were calculated to create tissue concentrations of morphine similar to those encountered in human death due to overdose. Morphine blood level plateau was attained after 1 h of perfusion. A fourth rabbit was used as a control. To evaluate drug concentrations, tissues were sampled using a coelioscopic technique. Approximately 400 eggs of Lucilia sericata, all of the same age category, were placed in eyes, nostrils and mouth of each rabbit carcass. Larvae and puparia were regularly collected from each rabbit for toxicological analysis. The concentrations of the drug in the tissues sampled were determined to be similar to those normally encountered in human overdoses and were correlated with the dosage of morphine that had been administered. Morphine was detected in all larvae and pupae fed on tissues from carcasses administered morphine, except for puparia from the colony fed on the R1 animal which received 12.5 mg/h dosage of morphine. All samples from the control rabbit were negative for morphine. Concentrations of morphine in larvae reared on rabbit carcasses containing morphine were 30 to 100 times lower than the concentrations found in the tissues. A correlation between the tissue concentrations and larval concentrations was found in only 3rd instar larvae (80 to 140 h following hatching). No correlations were found between administered dosages, tissue concentrations and younger larvae, prepuparial larvae or puparia.     

氯胺酮致小鼠产生类精神分裂症与NRG1、ErbB4 mRNA表达的相关性

目的探讨氯胺酮连续给药致小鼠产生的类似精神分裂症症状,与精神分裂症易感基因神经调节蛋白1（neuregulin-1,NRG1）及其受体ErbB4 mRNA表达的相关性,为研究精神分裂症的可能发病机制提供参考依据。方法50只雄性昆明种小鼠,随机分为生理盐水组、氯胺酮小剂量（25 mg/kg）、中剂量（50 mg/kg）、大剂量（100 mg/kg）组和氯氮平治疗组,腹腔注射给药,1次/d,连续7 d。氯氮平组在连续腹腔注射7d氯胺酮（1次/d,每次100mg/kg）后,再用氯氮平灌胃7d（1次/d,每次20mg/kg）。HE染色观察海马神经元的变化;采用逆转录-聚合酶链反应（RT-PCR）检测海马中NRG1及ErbB4 mRNA的表达。结果注射7d氯胺酮后,大剂量组海马区NRG1及ErbB4 mRNA的表达显著减少。结论氯胺酮诱导小鼠产生类似精神分裂症的症状,可能与海马区NRG1及ErbB4 mRNA的表达减少相关联。     

Determination of drug levels in larvae of Protophormia terraenovae and Calliphora vicina (Diptera: Calliphoridae) reared on rabbit carcasses containing morphine

Two species of blow flies (Diptera: Calliphoridae) were reared on tissues from rabbits administered different dosages of morphine. These species, Protophormia terraenovae and Calliphora vicina are among the first wave of insects colonizing a dead body. Two series of 3 rabbits were given dosages of 10, 20, and 40 mg/h of morphine over a 3 h period via ear artery perfusion. A morphine blood level plateau was attained after 1 h of perfusion. Two other rabbits were used as controls. Samples of tissues collected from rabbits using a coelioscopic technique were determined to have morphine concentrations similar to those encountered in human overdoses and were correlated with dosages of morphine administered. All samples from control rabbits were negative for morphine. Larvae and puparia of both species were regularly collected from each rabbit for toxicological analysis. Concentrations of morphine in larvae reared on rabbit carcasses containing morphine were significantly lower than concentrations found in the tissues. There was a decrease in concentration in morphine observed in transition from feeding 3rd instar larva to puparium. A correlation between larval concentration and tissue concentration was found only in feeding 3rd instar larvae.     

Quality management program and misadministrations--Nuclear Regulatory Commission. Final rule

The Nuclear Regulatory Commission (NRC) is amending regulations governing therapeutic administrations of byproduct material and certain uses of radioactive sodium iodide to require implementation of a quality management program to provide high confidence that the byproduct material or radiation from byproduct material will be administered as directed by an authorized user physician. The Commission believes this performance-based amendment will result in enhanced patient safety in a cost-effective manner while allowing the flexibility necessary to minimize intrusion into medical judgments. This amendment also modifies the notification, reporting, and recordkeeping requirements related to the quality management program and misadministrations.     

Tissue distribution of lidocaine after fatal accidental injection

The accidental death of a 64-year-old heart patient as a result of the injection of an incorrect dose of lidocaine is presented. The attending nurse inadvertently administered an intravenous bolus of 10 mL of 20% lidocaine (2g). The patient should have received 5 mL of 2% lidocaine (0.1 g). Such iatrogenic overdoses of lidocaine arise from confusion between prepackaged dosage forms. Lidocaine concentrations (mg/L or mg/kg were: blood, 30; brain, 135; heart, 106; kidney, 204; lung, 89; spleen, 115; skeletal muscle, 20; and adipose, 1.3. The results indicate that even during cardiopulmonary resuscitation as much as 38% of the administered dose of lidocaine may be found in poorly perfused tissue such as skeletal muscle and adipose.     

A critique of Callahan's utilitarian approach to resource allocation in health care

The rationale of this article is grounded in the liberal tradition. It places the individual at the center of concern, and attempts to fortify the individual's basic right to health care. Attention is focused on the writings of Daniel Callahan, arguing that his approach is too cold and detached, and that age should not serve as the decisive criterion. The criticism of his views on older patients and on patients in post-coma unawareness (PCU) stems from two different lines of reasoning: the medical and the moral-contractual. From the medical perspective, while age is an important variable in determining a patient's medical condition, there are other--no less important--factors that influence one's health. From the moral-contractual line of reasoning, liberal society should not desert its citizens at the time they need its help most. The age criterion is too simple, too general, too sweeping. It provides too convenient an answer to a tough and troubling question. Similarly, the argument with regard to PCU patients should be qualified, taking into account the age of the patient, the cause of the condition, and the length of time in state of unawareness.     

A cost comparison study of using global positioning system technology (electronic monitoring) in a medium secure forensic psychiatric service

‘Electronic Monitoring’ (EM) uses devices to monitor individuals’ whereabouts. In 2010, South London and Maudsley medium secure unit introduced EM to monitor individuals on leave. Analysis after two years revealed EM was associated with increased unescorted leave and reduced leave violation; however, comparative costs were not established. This study aims to compare costs of EM for patients on leave by comparing average total cost per patient with and without EM. Costs were compared before and after implementation of EM. Total cost of leave for each group was divided by number of patients to generate average total cost per patient. The average total cost per patient without EM was £1702; £1617 with EM. Although cost decreased, this was not statistically significant. The results showed no significant difference between average total costs per patient before and after EM. The finding of EM being cost-neutral is cautiously optimistic. Further trials are recommended.     

Plasma versus bone marrow desipramine: a comparative study

Correlation between plasma and bone marrow tricyclic antidepressants has not been studied before. Two groups of rabbits were given 10 and 20 mg of desipramine/kg body weight, respectively. Desipramine was administered to the animals once daily by mouth for 5 days. On the fifth day the animals were sacrificed and blood and bone marrow samples were collected and analyzed using a high performance liquid chromatographic (HPLC) method. Data showed that a correlation exists between bone marrow and blood desipramine. The bone marrow desipramine concentration increased as its blood levels increased. The average ratio of bone marrow to blood desipramine +/- S.D. (standard deviation) in both dosage groups was 37.2 +/- 4.46 with a range of 30.99-44.82. This investigation is promising and shows that bone marrow could be used as an alternative tissue in the absence of a suitable blood sample.     

Extracorporeal membrane oxygenation in the forensic setting: A series of 19 forensic cases

Extracorporeal membrane oxygenation (ECMO) employs vascular cannulation and a gas exchange circuit to provide support to patients with severely compromised cardiopulmonary function. ECMO is often the last intervention taken before death and thus presents a unique challenge to medical examiners. This study describes the characteristics of decedents on ECMO at the time of death, including clinical indications, types of circuit configurations, causes and manners of death, gross findings at autopsy, and therapeutic complications. Files of a regional medical examiner office within an academic medical center were searched for the period between 2013 and 2019. Nineteen cases were identified with a median age of 36 years. The circumstances surrounding the initial presentation included: sudden death, trauma, substance abuse, homicide, therapeutic complication, work-related injury, drowning, and hypothermia. The underlying causes of death included injury-related, as well as respiratory and cardiac-related natural diseases. The time spent on ECMO varied from less than 1 h to 10 months. Complications encountered due to ECMO included cannulation site bleeding, pneumohemopericardium, retroperitoneal hematoma, limb ischemia, clotting, and cannula dislodgement. The patient population likely to receive ECMO has significant overlap with death circumstances likely to be reported to the medical examiner. As ECMO therapy has become increasingly available, it is of importance for medical examiners and death investigators to be familiar with the procedure as well as its limitations. Familiarity with ECMO and its sequelae allows for the proper documentation of postmortem findings and fosters an informed determination of the cause and manner of death.     

Peculiarities of organization and performance of forensic medical expertise of the corpses of persons died of acute radiation injury

This paper is concerned with the topical problems of forensic medical diagnostics of acute radiation injury. The general and specific problems pertaining to the organization and performance of forensic medical expertise of the corpses of persons deceased by reason of acute radiation sickness are considered. The special emphasis is laid on the selection of autopsy materials and their referring to specialized laboratories for the additional investigation. The methods of anti-radiation protection of the medical personnel are considered.     

Would responsible medical lawyers lose their patients?

This essay presents an analytic approach to understanding patients' responsibilities. Prompted by arguments in Margaret Brazier's article 'Do No Harm--Do Patients Have Responsibilities Too?', the paper demonstrates how medical lawyers can attempt to answer the questions Brazier raises, particularly regarding the translation of ethical responsibilities into legal ones. It suggests that the expansive nature of medical law as a discipline renders increasingly unhelpful the paradigm 'autonomous patients' found in a narrowly understood medical ethics. The great variety of contexts in which analysis takes place--some more, and some less 'medical'--implies a need in each case to presume that there might be radical variation in the responsibilities (legal and ethical) of different patients. It is therefore argued that instead of a one-size-fits-all paradigm of 'patients', always possessive of the same rights and freedoms, medical lawyers must be prepared to conduct analysis around more particular, nuanced concepts of the patient, and ultimately in a frame of legal and political rather than moral theory.     

Draft guidance for industry on developing medical imaging drugs and biologics; availability--FDA. Availability of guidance

The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled "Developing Medical Imaging Drugs and Biologics." This draft guidance is intended to assist developers of drug and biological products used for medical imaging, as well as radiopharmaceutical drugs used in disease diagnosis, in planning and coordinating the clinical investigations of, and submitting various types of applications for, such products. The draft guidance also provides information on how the agency will interpret and apply provisions in the proposed regulations for in vivo radiopharmaceuticals used for diagnosis and monitoring, which published in the Federal Register of May 22, 1998 (63 FR 28301).     

Exemption from import/export requirements for personal medical use. Final rule

The Drug Enforcement Administration (DEA) is amending its regulations to expressly incorporate the restrictions on personal use importation imposed by Congress in 1998 and to expand upon those restrictions to curtail the diversion that has continued even after the 1998 congressional amendment. Specifically, DEA is limiting to 50 dosage units the total amount of controlled substances that a United States resident may bring into the United States for legitimate personal medical use when returning from travel abroad at any location and by any means. This regulation will help prevent importation of controlled substances for unlawful use while still accommodating travelers who have a legitimate medical need for controlled substances during their journey.     

Criteria for the release of individuals administered radioactive materials--NRC. Final rule

The Nuclear Regulatory Commission (NRC) is amending its regulations concerning the criteria for the release of patients administered radioactive material. The new criteria for patient release are based on the potential dose to other individuals exposed to the patient. The new criteria are consistent with the recommendations of the National Council on Radiation Protection and Measurements (NCRP) and the International Commission on Radiological Protection (ICRP). This final rule required the license to provide written instructions to patients on how to maintain the doses to others as low as is reasonably achievable if the total effective dose equivalent to any other individual exposed to the released patient is likely to exceed 1 milisievert (0.1 rem). This final rule responds to three petitions for rulemaking regarding the criteria for release of patients administered radioactive material.     

Diethyl phosphates accumulation in rabbits' hair as an indicator of long term exposure to diazinon and chlorpyrifos

Long term exposure to organophosphate pesticides can be evaluated by quantitative analysis of their non-specific metabolites in hair matrix. The aim of this study was to determine whether these metabolites can be internally incorporated into the hair of rabbits exposed to diazinon and chlorpyrifos. The influence of dose and dose duration of each pesticide dosage were investigated. Three groups of rabbits were exposed to different dosages of diazinon (3.0 and 6.0mg/kg/day) and chlorpyrifos (18.0mg/kg/day) via drinking water. Hair samples were collected every month and analyzed for diethyl phosphate (DEP) and diethyl thiophosphate (DETP) by gas chromatography-mass spectrometry (GC-MS). The mean concentrations of the low-dose treated group, ranged from 112 to 257pg/mg for DEP and from 295 to 515pg/mg for DETP in hair. The high-dose treated group demonstrated a range of mean concentrations from 142 to 585pg/mg for DEP and from 406 to 988pg/mg for DETP in hair. For the chlorpyrifos treated group, the concentrations ranged from 138 to 1070 for DEP and from 554 to 886pg/mg for DETP. Analysis revealed the incorporation of these metabolites into the rabbit hair in a dosage and dose duration-dependent manner. These data confirms the ability of using hair analysis for diethyl phosphates to assess long-term OP exposure.     

Labor condition applications and requirements for employers using aliens on H-1B visas in specialty occupations--Department of Labor. Interinal final rule; request for comments

The Employment and Training Administration (ETA) and the Employment Standards Administration (ESA) of the Department of Labor (DOL or Department) are promulgating regulations governing the filing and enforcement of labor condition applications filed by employers seeking to use aliens in specialty occupations on H-1B visas. Under the Immigration and Nationality Act (INA), as amended by the Immigration Act of 1990 (Act), an employer seeking to employ an alien in a specialty occupation on an H-1B visa is required to file a labor condition application with, and receive the approval of, DOL before the Immigration and Naturalization Service (INS) may approve an H-1B visa petition. The labor condition application process will be administered by ETA; complaints and investigations regarding labor condition applications will be the responsibility of ESA.     

Comparative studies on tissue distributions of organophosphorus, carbamate and organochlorine pesticides in decedents intoxicated with these chemicals

This paper describes the tissue distributions of dichlorvos, an organophosphate, chlorpyrifos-methyl, an organophosphorothioate, methomyl, a carbamate, and endrin, an organochlorine, in three individuals (Cases 1-3) who died after ingesting insecticidal preparations containing these chemicals. In Case 1 involving dichlorvos and chlorpyrifos-methyl, no dichlorvos was detected in most of the blood and tissue samples. Tiny amounts of dichlorvos (0.067 mg/L and 0.027 mg/L) were detected in the vitreous humor and cerebrospinal fluid, respectively. The chlorpyrifos-methyl concentrations in the blood samples were very site-dependent with a range of 0.615-2.24 mg/L. The tissue concentrations of chlorpyrifos-methyl were within the range 0.379-8.60 mg/kg. The total amounts of dichlorvos and chlorpyrifos-methyl in the stomach were 879 and 612 mg, respectively. The serum cholinesterase activity was 3 IU/L/37 degrees C. In Case 2 involving methomyl, the methomyl concentrations in the blood samples were very site-dependent with a range of 0.56-4.75 mg/L. The tissue concentrations of methomyl were 2.61 mg/kg or less, no methomyl being detected in the spleen, liver and kidney. The methomyl concentrations in the cerebrospinal fluid and vitreous humor were 5.37 and 4.75 mg/L, respectively. The stomach contained 85 mg methomyl. The serum cholinesterase activity was 73 IU/L/37 degrees C. In Case 3 involving endrin, the victim underwent medical treatment for 7 h after ingesting an endrin preparation. The differences in the endrin concentrations among the blood samples were small, with a range of 0.353-0.615 mg/L. The tissue concentrations of endrin were within the range 0.467-13.3 mg/kg. The endrin in the stomach (66 mg) was adsorbed almost completely on the activated charcoal that was administered for medical treatment.     

从刑法理论看医疗行为的正当性根据

医疗行为从表面看似乎给人体造成一定伤害 ,但其主观目的在于治病救人 ,客观上有利于患者和社会 ,因此具有正当性。但医疗行为的正当性具有严格的条件限制。本文根据允许的危险、受害人承诺、义务冲突等刑法理论 ,对医疗行为的正当性根据作了进一步探讨。     

Medicolegal causation: a source of professional misunderstanding

The authors of this Comment--a lawyer and a physician--suggest that most physicians who are called upon to testify concerning medical issues in personal injury litigation do not understand that judges and attorneys view "causation" quite differently than do members of the medical community. For example, medical practitioners tend to be concerned with all possible causes of the patient's current medical condition, whereas legal practitioners in personal injury cases generally focus on a particular event as possibly precipitating, hastening, or aggravating a particular aspect of the patient's condition to the extent that the event in question is, in legal language, the "proximate cause" of an injurious result. The authors summarize and analyze the differences--and the occasional similarities--between the medical and the legal approaches to causation, in the hope that they will thereby (1) contribute to greater understanding by the two professions of each other's theory and practice, and (2) help the expert medical witness to be more comfortable and more effective in his courtroom role.