An unusual case of death probably triggered by the association of buprenorphine at therapeutic dose with ethanol and benzodiazepines and with very low norbuprenorphine level.

Buprenorphine is largely prescribed for maintenance treatment in opioid dependence due to its safety profile. Nevertheless, fatalities at therapeutic dose have been described when associated with other central nervous system depressants, such as ethanol or benzodiazepines. Here, we report a case of death due to association of buprenorphine at therapeutic dose with benzodiazepines and ethanol. Although toxicity has been often attributed to its metabolite norbuprenorphine rather than to buprenorphine itself, in our case, norbuprenorphine was not detected in urine and bile and only in traces in blood. Moreover, the presence in blood of free buprenorphine but not of glucuronide metabolites argues for an unusual early death, at the beginning of buprenorphine metabolism. We propose that in the context of prior toxic impregnation, buprenorphine directly (and not via its metabolite norbuprenorphine) acted as a triggering factor by blocking the ventilatory response, rapidly leading to fatal respiratory depression.

Assessment of abdominal branch vessel patency after bare-metal stenting of the thoracoabdominal aorta in a human ex vivo model of acute type B aortic dissection.

OBJECTIVE: The purpose of this study was to assess the efficiency of bare-metal stenting of the thoracoabdominal aorta in a human ex vivo model of acute type B aortic dissection and the impact of this approach on the patency of the visceral and renal arteries. METHODS: Fifteen human cadaveric aortas were harvested. Type B aortic dissections were surgically initiated 2 cm below the left subclavian artery. Aortas were thereafter connected to a bench top pulsatile flow to induce propagation of the dissection. A 5-mm 30° lens (Richard Wolf, Vernon Hills, Ill) was introduced successively into the false lumen and the true lumen to monitor the propagation of the dissection. Bare-metal stents were deployed into the true lumen from the primary entry tear to the infrarenal aorta. Measurement of systolic pressure was taken within the abdominal branch vessels before and after stenting. A pressure gradient drop of 15 mm Hg or more after bare-metal stenting was considered hemodynamically relevant. RESULTS: Dissection was propagated at least to the renal aorta in 11 cases (73%) and to the infrarenal aorta in 3 cases (20%). Of the 60 abdominal branch vessels studied, 22 (36.7%) were supplied by the false lumen. After extensive aortic bare-metal stenting, complete reattachment of the dissection flap was observed in all cases. Regarding visceral and renal artery patency after bare-metal stenting, a significant pressure gradient drop was reported in 54.5% (n = 12) when these arteries were supplied by the false lumen, whereas those originating from the true lumen had a significantly less common pressure gradient drop (7.9% [n = 3]; P < .0001). CONCLUSIONS: Bare-metal stenting in this model of acute type B aortic dissection was effective in true lumen reexpansion but induced a high (54.5%) rate of significant pressure drop in the visceral and renal arteries when they were supplied by the false lumen.

Human ex-vivo model of Stanford type B aortic dissection.

OBJECTIVE: To report a new human ex vivo model of type B aortic dissection (TBAD) and to assess if the locations of the primary entry tear determine the patterns of dissection propagation. METHODS: Twenty fresh human aortas were harvested. TBADs were surgically initiated 2 cm below the left subclavian artery at four different locations (lateral, n = 5; medial, n = 5; anterior, n = 5; posterior, n = 5). Aortas were thereafter connected to a bench-top pulsatile flow model to induce antegrade propagation of the dissection. RESULTS: Antegrade propagation of the dissection was achieved and reached at least the celiac trunk (CT) in all the cases. Dissection was propagated to the renal aorta in 16 (80%) and infrarenal aorta in seven cases (35%). Left renal artery with or without the CT originated more often from the false channel when primary entry tear was lateral. Right renal artery and the CT most often originated from the false channel when primary entry tear was medial. When the CT was the only one originating from the false channel, primary entry tear was more often anterior, whereas when it originated from the true channel, it was more often posterior. CONCLUSIONS: This human ex vivo model of TBAD is reproducible, since, in all the aortas, extended dissection was achieved and provides the first model of human aortic dissection with infrarenal aorta extension allowing future assessment of endovascular devices developed for human use. Furthermore, it allows clarification of the patterns of aortic dissection propagation and visceral and renal artery involvement according to the site of the primary entry tear.

Toxicity and death following recreational use of 2-pyrrolidino valerophenone.

BACKGROUND: Consumption of substituted cathinones, frequently called 'legal highs' or 'designer drugs', is increasing in the European Union. In July 2012, the French Medicine Agency listed the substituted cathinone's chemical family as narcotic and psychotropic substances, to restrict their use and distribution. We present, here, the first documented cases of recreational use of 2-pyrrolidino valerophenone (PVP) associated with death for one patient, with post-mortem toxicological analysis. CASE REPORTS: Two men purchased the legal high Energy-3 (NRG-3). It can be sold as laboratory reagent and is available from Internet. The oldest died of sudden cardiac arrest. The other experienced visual hallucinations and psychotic symptoms for 24 h. He also presented bilateral mydriasis, sinus tachycardia and rhabdomyolysis. He reported an occasional intranasal use of NRG-3. Analysis of the powder and blood and urine from both men revealed the presence of PVP. DISCUSSION AND CONCLUSION: PVP belongs to the substituted cathinones chemical family. These cases highlight the need for emergency physicians, toxicologists and networks of toxicovigilance to control the use of these substances and their dangers, quickly identify cases of severe poisoning associated with the use of new drugs and to develop detection methods.

A case of drug-facilitated sexual assault involving 3,4-methylenedioxy-methylamphetamine.

Typical scenarios of drug-facilitated sexual assaults usually involve victims having ingested a drink after which they had little, partial or no recollection of events for a period of time. We were surprised by the case of a woman who was sexually assaulted and described a state of amazement, leading to an incapacity to resist physically or verbally to her aggressor, and who remembered everything. Alcohol was first suspected but toxicological analysis revealed the presence of 3,4-methylene-dioxy-methylamphetamine (MDMA, Ecstasy). In the literature review, a few cases of sexual assault involving involuntarily MDMA intake are described.

Methadone-related deaths in Montpellier and Region, from 2000 to 2010.

PURPOSE: The objectives of this analysis were to assess the role of methadone and related substances in death occurring, discussing methadone blood concentrations and the contribution of the autopsy to the accountability of methadone in the death process. METHOD: We retrospectively analyzed all forensic cases positive for methadone from January 2000 to December 2010, in Montpellier and the region served by our laboratory. RESULTS: During the study period, 64 cases of deaths (11 women, 53 men) with methadone detection were recorded. A progressive increase between 2001 (2 cases) and 2010 (8 cases) was observed. The median age was 33 years old. An autopsy was available in 56.3% of cases. The most frequent finding at the autopsy was non-specific asphyxia death signs (67.6%). Tolerance to opioids was documented in 21 cases. The methadone blood concentrations ranged from 1 to 2 800 ng/mL (59 cases, median value 330 ng/mL). Most of the cases (88%) were polydrug intoxications. The most commonly associated drugs were benzodiazepines (61%), cannabinoids (28%), opioids (19%) and cocaine (12.5%). CONCLUSION: During a 11-year period, toxicological analyses related to 1991 death cases were performed at the Toxicology Laboratory of Montpellier University Hospital. Of these patients, 64 deaths were possibly related to methadone. Several relevant elements (biological analysis and autopsy) were used to attribute the deaths to the sole methadone (12 cases) or to methadone and associated substances (8 cases).

Rapid detection of the deltaF508 mutation in single cells using DHPLC: implications for preimplantation genetic diagnosis.

PURPOSE: Practice of preimplantation genetic diagnosis (PGD) requires efficient amplification and analysis techniques. We have tested Denaturing High Performance Liquid Chromatography (DHPLC) to screen the deltaF508 mutation in heterozygous single cells in order to assess its usefulness for PGD of cystic fibrosis. METHODS: One hundred and two single lymphocytes--including N/N and N/deltaF508--were studied. F508 locus was amplified by nested PCR followed by the analysis of PCR products by DHPLC in non-denaturing conditions. RESULTS: On the basis of PCR-amplified product analysis, total efficiency of amplification was 98.78% (101/102), and allele dropout (ADO) rate was 3.7% (3/81). For each sample, results were obtained in less than 4 min with high resolution. CONCLUSIONS: DHPLC is a rapid and efficient technique to detect the deltaF508 mutation in single cells and is therefore appropriate for clinical application of preimplantation genetic diagnosis of cystic fibrosis.