Testing for midazolam and oxycodone in blood after formalin‐embalmment: About a complex medico‐legal case

The stability of compounds in formalin solution is an important factor for drug analysis in a toxicological investigation. In this article, the authors report a complex medico‐legal case involving midazolam and oxycodone. The complexity of this case comes from the fact that the body was embalmed with formalin solution before the autopsy. This technique, called thanatopraxy, allows the preservation of corpses from decomposition, the destruction of a maximal number of micro‐organisms, and the presentation of the body with a natural appearance to the family. Unfortunately, when thanatopraxy is performed before the collection of biological specimens, the toxicological results are not representative of the time of the death. In addition, the interpretation of the results is difficult, because formalin can cause oxidation of xenobiotics present in the body at the time of the death, alter the pH of the tissues and dilute the compounds. To document the chemical stability of midazolam and oxycodone in formalin solution and interpret the results, a stability study was conducted for 21 days. Blood containing midazolam and oxycodone was spiked with formalin, kept at 4°C and regularly tested for both drugs. This study showed a rapid degradation of midazolam and oxycodone (85% during the first 24 hours for oxycodone). In the peripheral blood of the victim, methanol (1.31 g/L), midazolam (74ng/mL) and oxycodone (152 ng/mL) were identified. According to the stability study, the measured concentrations in formalin fixed‐tissues are to be interpreted very carefully, knowing that significant degradation has occurred.     

Clinical and histopathological correlations of fecal calprotectin release in colorectal carcinoma

AIM:To determine calprotectin release before and after colorectal cancer operation and compare it to tumor and histopathological parameters.METHODS:The study was performed on patients with diagnosed colorectal cancer admitted for operation.Calprotectin was measured in a single stool sample before and three months after the operation using an enzymelinked immunosorbent assay(ELISA).Calprotectin levels greater than or equal to 50μg/g were considered positive.The compliance for collecting stool samples was assessed and the value of calprotectin was correlated to tumor and histopathological parameters of intra-and peri-tumoral inflammation.Surgical specimens were fixed in neutral buffered formalin and stained with hematoxylin and eosin.Staging was performed according to the Dukes classification system and the 7th edition tumor node metastasis classification system.Intra-and peri-tumoral inflammation was graded according to the Klintrup criteria.Immunohistochemical quantification was performed for MPO,CD45R0,TIA-1,CD3,CD4,CD8,CD57,and granzyme B.Statistical significance was measured using Wilcoxon signed rank test,Kruskal Wallis test and Spearman’s rank correlation coefficient as appropriate.RESULTS:Between March 2009 and May 2011,80 patients with colorectal cancer(46 men and 34 women,with mean age of 71±11.7 years old)were enrolled in the study.Twenty-six patients had rectal carcinoma,29 had left-side tumors,23 had right-side tumors,and2 had bilateral carcinoma.In total,71.2%of the patients had increased levels of calprotectin before the operation(median 205μg/g,range 50-2405μg/g)and experienced a significant decrease three months after the operation(46μg/g,range 10-384μg/g,P<0001).The compliance for collecting stool samples was 89.5%.Patients with T3 and T4 tumors had significantly higher values than those with T1 and T2 cancers(P=0.022).For all other tumor parameters(N,M,G,L,V,Pn)and location,no significant difference in calprotectin concentration was found.Furthermore,the calprotectin levels and histological grading of both peri-and intra-tumoral inflammation was not correlated.Additional testing with specific markers for lymphocytes and neutrophils also revealed no statistically significant correlation.CONCLUSION:Fecal calprotectin decreases significantly after colorectal cancer operation.Its value depends exclusively on the individual T-stage,but not on other tumor or histopathological parameters.     

Prevalence and risk factors of cataract after chemotherapy with or without central nervous system irradiation for childhood acute lymphoblastic leukaemia: an LEA study

Corticosteroid and central nervous system (CNS) irradiation can induce cataract in childhood lymphoblastic leukaemia survivors. Few prospective studies with systematic ophthalmological evaluation have been published. Cataract was prospectively assessed by serial slip lamp tests in 517 patients. All had acute lymphoblastic leukaemia, all had been treated by chemotherapy with or without CNS irradiation, and none had received haematopoietic stem cell transplantation. Median ages at last evaluation and follow‐up duration from leukaemia diagnosis were 16·8 and 10·9 years, respectively. Cataract was observed in 21/517 patients (4·1%). Cumulative incidence was 4·5 ± 1·2% at 15 years and reached 26 ± 8·1% at 25 years. CNS irradiation was the only risk factor: prevalence was 11·1% in patients who had received irradiation and 2·8% in those who did not. We did not detect any steroid dose effect: cumulative dose was 5133 and 5190 mg/m² in patients with and without cataract, respectively. Cataract occurrence did not significantly impact quality of life. We conclude that, in the range of steroid dose reported here, the cataract risk proves very low 15 years after treatment without CNS irradiation but an even more prolonged follow‐up is required because of potential very late occurrence.     

Acute promyelocytic leukaemia is characterized by stable incidence and improved survival that is restricted to patients managed in leukaemia referral centres: a pan‐Canadian epidemiological study

Timely diagnosis and care are major determinants of the outcome in acute promyelocytic leukaemia (APL), a malignancy whose incidence may be increasing. The Canadian Cancer Registry (CCR) and health system represent valuable settings to study APL epidemiology. We analysed the CCR, which contains data on all Canadians with APL. To provide clinical information lacking in the CCR, we obtained data from five leukaemia referral centres during a similar time period. Between 1993 and 2007, there were 399 APL in Canada. Age‐standardized incidence was 0·083/100 000 and was stable over time. The early death (ED) rate was 21·8% (10·6% in patients <50 years old and 35·5% for those aged >50 years), with no improvement over time. Five‐year overall survival (OS) was 54·6% (73·3% in patients <50 years; 29·1% older patients). In the referral cohort, 131 patients were diagnosed between 1999 and 2010. ED was 14·6% and 2‐year OS was 76·5%. Within this cohort, ED and OS improved over time, although advanced patient age remained an adverse determinant of OS. In Canada, APL incidence is unexpectedly low and temporally stable. ED was higher than reported in clinical trials, but similar to reports from other registries. In contrast, ED was lower in referral centres and improved with time.     

Architecture,théorie du soin en psychiatrie et politique. De la forme au sens

When evoking the insane asylum, Esquirol wrote in 1822 : “In the hands of a skillful physician it is the most powerful agent against mental illnesses”, he did not refer only to the architectural space arrangement of the asylum but to its global conception of the care environment, and this notion of care environment is more complex than it seems. The significant link he introduced could lead to confuse that which belongs to care and that which depends on the environment in which it is given. Moreover, history shows this subtle exchange between psychiatry and architecture. Within the research of the therapeutic impact that an ideal society could have on mental illness, the link between moral treatment and the architecture of the classical asylum is well known as is that between the village hospital with institutional psychotherapy. But, on the other hand, who remembers that the debate between Marxism and psychoanalysis within psychiatry had important repercussions on the architectural and environmental modalities provided to care for the mentally ill ?     

Ventricular allorhythmia during infarct-related ventricular tachycardia

Ventricular allorhythmia is an electrocardiogram feature leading to a pattern of "regularly irregular" arrhythmia mainly reported during non-life-threatening organized atrial tachycardia. We report the infrequent case of a patient presenting with ventricular allorhythmia during infarct-related ventricular tachycardia. The potential mechanisms of this tachycardia are discussed.