Identification of a novel HLA allele, HLA-B*41:50, in a French individual.

The novel HLA-B*41:50 allele differs from HLA-B*41:01:01 by a single nucleotide substitution at codon 116.

Identification of a novel HLA allele, HLA-B*15:416, in a bone marrow hematopoietic stem cell donor.

The novel HLA-B*15:416 allele differs from HLA-B*15:01:01:01 by a single nucleotide substitution at codon 114.

Identification of a novel HLA allele, HLA-B*08:163, in a platelet donor.

The novel HLA-B*08:163 allele differs from HLA-B*08:01:01:01 by a single nucleotide substitution at codon 105.

Conjugal violence: a comparison of violence against men by women and women by men.

Because few studies demonstrated the types of violence performed by women, the aim of our study was to access violence men against women as well as women against men. A retrospective study was performed based on all the medical certificates for victims who consulted our centre specialized in assault victims. Eleven percent of the victims were men (81 men, 626 women). Episodes of violence were most often repeated against women than men (p < 0.05). Injuring, in most cases mild, were more frequently found in men than women (p < 0.01). They were primarily cutaneous in 66% of cases (85% men, 64% women) and severe in 5% of cases i.e. fractures, with no difference in gender. Three cases of sexual assault and one case of chemical submission was observed in women. Insults were made more often by men than by women (p < 0.002). A psychological impact was more frequently found in women than in men (p < 0.01). The duration of the total incapacity (incapacité totale de travail = ITT) was less than 0-3 days in most cases, and this occurred more often in 91% men than in 65% women (p < 0.01). Consultations for domestic violence occur less frequently in men than in women. Men present more often with injuries that are less severe compared to those observed in women. In contrast, the psychological impact is less frequent in men. Also episodes of violence were most often repeated when the aggressor was a man.

Identification of a novel HLA allele, HLA-B*53:39, in a Guadaloupean individual.

The novel HLA-B*53:39 allele differs from HLA-B*53:01 by a single nucleotide substitution at codon 45 (ACG>AAG).

HLA-B*51:79 is a novel allele associated with a conserved haplotype.

The B*51:79 allele displays a conserved haplotype association with HLA-A*68:01, C*01:02, DRB1*14:01 and DQB1*05:03.

A murine model of cow's milk protein-induced allergic reaction: use for safety assessment of hidden milk allergens.

BACKGROUND: Masked allergens in processed food products can lead to severe allergic reactions following unintentional ingestion. We sought to develop a murine model for the detection of hidden cow's milk proteins (CMP). This study aimed to induce cow's milk allergy in mice, to characterize the anaphylaxis induced by CMP in this model, and to validate its reliability using three margarines manufactured with (A) or without (B, C) milk, sharing the same production line. MATERIALS AND METHODS: Three-week-old BALB/c mice were sensitized intragastrically with CMP plus cholera toxin and boosted 6 times at weekly intervals. CMP-sensitization status was monitored by skin tests, and measurement of CMP-specific IgE and IgG1 levels. On day 44, the minimal threshold of clinical reactivity to CMP in terms of anaphylaxis was determined by performing a dose response of intraperitoneal CMP challenge. Under the same conditions, anaphylaxis was evaluated in CMP-sensitized mice after challenge with protein extracts of margarines A, B or C. RESULTS: Sensitization to CMP was demonstrated by positive skin tests and increased CMP-specific IgE and IgG1. The minimal clinical reactivity threshold corresponding to 0.1 mg CMP elicited detectable anaphylaxis evidenced by clinical symptoms, a decrease in breathing frequency, and increased plasma histamine upon challenge. Similarly, challenges with margarine A containing CMP demonstrated anaphylaxis, whereas those with B or C did not elicit any detectable allergic reaction. CONCLUSION: This study shows that our murine model of CMP-induced anaphylaxis is useful for investigating the allergenic activity and the assessment of margarines with respect to milk.

HLA-B*0749N: the first HLA-B*07 null allele.

In the present article, we report the identification of the first HLA-B*07 null allele found in a Polish patient awaiting a kidney allograft. A discrepant result obtained between serological typing (HLA-B "blank") and high-resolution molecular typing using PCR-SSP method (HLA-B*070201 allele) suggested the presence of a null allele. Genomic DNA sequencing of the HLA-B*07 allele revealed a single nucleotide substitution at the 3' end of the exon 4 leading to a premature stop codon.

Arteriocolic fistulae due to a stab wound: a rare cause of lethal lower gastrointestinal bleeding.

The authors describe the first reported case of lethal lower gastrointestinal bleeding due to an iliocolic fistulae following a single stab wound. They also discuss the pathophysiology of the enterovacscular fistulae, as well as a review of the literature and assess forensic characteristics. This unusual case underlines the importance of being aware of the victim's history in arteriocolic fistulae due to a stab wound.

Sudden death from a "broken heart" in a young woman.

A case of ruptured myocardial infarct in a young woman with no previous medical history is presented, as well as a review of the literature and forensic aspects are discussed.

Lethal paradoxical cerebral vein thrombosis due to suspicious anticoagulant rodenticide intoxication with chlorophacinone.

Superwarfarin exposure is a growing health problem, described in many countries. The authors report a case of suspicious chlorophacinone poisoning with a problematic diagnosis. They review the literature and discuss particularities of anticoagulant rodenticide intoxication, as well as the apparent contradiction between anticoagulant intoxication and lethal thrombosis.

Fatal and non-fatal bilateral delayed carotid artery dissection after manual strangulation.

Carotid artery (CA) dissection and/or thrombosis may occur in a number of medical and forensic relevant situations. However, post traumatic carotid artery dissection is considered rare, and often underestimated due to possible delayed presentation. We describe two cases of carotid artery dissection following strangulation with delayed symptoms as well as discuss medical diagnostic problems and their forensic implications.

[Inductively coupled plasma and clinical biology. Toxicological applications]. / Intérêt de la torche à plasma en biologie clinique. Quelles applications en toxicologie?

The multi-elementary quantitation method using inductively coupled plasma mass spectrometry has been widely developed for use with biological fluids. Many elements can be quantified simultaneously in biological fluids, including: Li, Be, B, Al, Mn, Co, Ni, Cu, Zn, Ga, Ge, As, Se, Rb, Sr, Mo, Pd, Cd, Sn, Sb, Te, Ba, W, Pt, Hg, Tl, Pb, Bi, U. The validation procedure is described by the French Society of Clinical Biology. Results for urine are corrected after creatinine determination. We report applications in clinical toxicology and forensic toxicology. Advances in inductively coupled plasma mass spectrometry in the field of clinical biology are particularly important for toxicological analysis. This powerful tool is helpful for better patient care and for the search for cause of death.

Fatal overdoses of tramadol: is benzodiazepine a risk factor of lethality?

Tramadol is a centrally acting analgesic agent used in the treatment of mild to moderate pain. It has a low affinity to opioid receptors and inhibits the reuptake of norepinephrin and serotonin producing an analgesic action by blocking nociceptive impulses in the spine. Although 21 drug-combined fatalities including tramadol have been reported, only two fatal overdoses in adults with tramadol alone have been reported to date. We report four additional lethal intoxications, assess the toxicity of tramadol, the detection method and the possible interaction with other central nervous system (CNS) depressants, particularly benzodiazepines. Similarities between tramadol and buprenorphine are discussed, and a possible cytochrome P450-based interaction between tramadol and benzodiazepine is considered. To our knowledge, this relationship has never been reported in the literature.

Elicitation of the allergic reaction in beta-lactoglobulin-sensitized Balb/c mice: biochemical and clinical manifestations differ according to the structure of the allergen used for challenge.

BACKGROUND: Mouse models of allergy are used to study the mechanisms of induction and perpetuation of bronchopulmonary hyper-reactivity (BHR) as related to eosinophils and specific IgE. OBJECTIVE: Our aim was to adapt the current model for the study of bovine beta-lactoglobulin (BLG), a major cow's milk allergen, and to further analyse the mechanisms of the acute and late allergic reaction. METHODS: Female Balb/c mice were sensitized intraperitoneally with BLG and the influence of the adjuvant and of the BLG dose on the IgE response was analysed, IgE and IgG1 epitopes being characterized. Once optimized, this model was applied to the study of the active phase of allergy in the respiratory tract after a single airway challenge using native or denatured BLG, which contains only linear epitopes. RESULTS: An immediate allergic reaction was characterized by the rapid release of histamine into the bronchoalveolar lavage fluids. Prostaglandin (PG)D2 was only present when the standard histamine-releasing agent compound 48/80 or denatured BLG were used as triggers, whereas native BLG induced leukotriene release. Twenty-four hours after challenge, BHR, eosinophil influx, IL-4 and IL-5 production, plasma exudation and mucus production were very much increased, differently depending on the allergen structure, and indicated the occurrence of the late allergic reaction. Our results show that the murine model can be used to study the mechanisms of allergy to clinically relevant antigens, such as those contained in cow's milk. The acute allergic reaction, which depends on the structural feature of the allergen, is composed of two distinct pathways characterized by peptido-leukotrienes or PGD2 production, which may result from distinct activation intensities of mast cells, leading to distinct late reactions. CONCLUSION: This study thus demonstrates a clear link between the structural feature of a protein, and the physiopathology of the experimental asthmatic reaction.

Persistence of bronchopulmonary hyper-reactivity and eosinophilic lung inflammation after anti-IL-5 or -IL-13 treatment in allergic BALB/c and IL-4Ralpha knockout mice.

BACKGROUND: Antigen-induced bronchopulmonary hyper-reactivity (BHR) is generally associated with eosinophilia. It involves cytokines produced by Th2 lymphocytes, including IL-4, IL-5 and IL-13, which are implicated in IgE production, eosinophil differentiation and attraction, and related events relevant to allergic inflammation, whose mechanisms remain unclear. OBJECTIVE: To investigate the mechanisms by which Th2 cytokines mediate eosinophilia and subsequent BHR using ovalbumin (OVA)-immunized and OVA-challenged IL-4Ralpha-/- and IL-4-/- mice, which fail to transduce and/or to produce IL-4 and IgE as compared with wild type (WT) mice, and specific neutralizing antibodies. METHODS: On days 0 and 7, mice were immunized subcutaneously (s.c.) with OVA. At day 14, anti-IL-5 or anti-IL-13 antibodies were administered intranasally and/or intravenously before allergenic challenge. Different functional and cellular parameters were studied in vivo and cytokine production was followed with a newly described ex vivo procedure using lung explants. RESULTS: IL-4Ralpha-/- and IL-4-/- mice developed BHR and pulmonary eosinophilia, even though eosinophil recruitment to the bronchoalveolar liquid lavage (BALF) was reduced. In vivo, IL-4-/- and IL-4Ralpha-/- mice produced, respectively, no or reduced amounts of IL-5 in the BALF/serum as compared with WT mice, whereas no IL-13 in the BALF was detected. By contrast, ex vivo, surviving lung explants from WT and IL-4-/- or IL-4Ralpha-/- mice produced IL-13 and large amounts of IL-5. The neutralization of IL-5 in vivo (BALF and serum) and ex vivo (from lung explant) in IL-4Ralpha-/- and WT mice failed to suppress BHR and lung eosinophilia, and to modify IL-13 production ex vivo. In addition, neutralization of IL-13 in vivo from lung explant also failed to abrogate BHR and lung eosinophilia, whereas IL-5 was unchanged. CONCLUSION: Antigen-induced BHR can develop independently from IL-4, IL-5 or IL-13 and from the IL-4alpha receptor chain, suggesting a possible novel IL-4, IL-5 and IL-13-independent pathway for the development of BHR in allergic BALB/c mice. The failure of IL-5 or IL-13 antibodies to prevent BHR in IL-4Ralpha-/- mice suggests that neither is indispensable for BHR but does not exclude a role for lung tissue eosinophilia.

Two successive hepatitis C virus infections in an intravenous drug user.

We report the case of an occasional intravenous drug user who developed two successive hepatitis C virus (HCV) infections. The first infection led to seroconversion (anti-HCV antibodies detected) and the detection of HCV RNA in serum. After a spontaneous recovery (normalization of alanine aminotransferase levels and HCV RNA clearance), a second HCV infection was observed, with the recurrence of HCV viremia. Antibody directed against HCV serotype 1 was detected throughout the follow-up monitoring, but two different HCV strains were identified during the two infectious episodes: genotype 1a for the first and genotype 3a for the second. This observation shows that primary HCV infection does not confer protective immunity against subsequent infection with viruses of other genotypes. This may hamper the development of a vaccine. Conflicting results were obtained in genotyping and serotyping assays, suggesting that the serotyping method cannot be used to identify the HCV type in patients, such as intravenous drug users, who are exposed to successive HCV infections.

Giant cervical epidural veins after lumbar puncture in a case of intracranial hypotension.

A 29-year-old woman presented with dilated epidural veins and incapacitating headache after undergoing a lumbar puncture. Two months later, the results of follow-up MR imaging were normal. These findings suggest that temporary dilation of the epidural vein may occur in association with post-lumbar puncture intracranial hypotension syndrome. In these cases, it seems useful to confirm whether the patient has recently undergone a lumbar puncture.

Fatal case of dichloromethane poisoning.

A 47-year-old man was found dead in a factory where dichloromethane (DCM) tanks were stocked. He was making an inventory of the annual stock of DCM contained in several tanks (5- to 8000-L capacity) by transferring the solvent into an additional tank with the help of compressed air. During this operation, one of the tanks overflowed and the man, who was not wearing any protection, was intoxicated. Autopsy showed digestive, suprarenal, and liver bleeding. Blood was also found in the trachea. DCM was identified by headspace gas chromatography-mass spectrometry (GC-MS). A headspace gas chromatography-flame ionization detection technique (GC-HS-FID) optimized for quantitation in biological fluids, organs and viscera was established at autopsy. The following concentrations of DCM were found: blood (150 mg/L), urine (2.0 mg/L), gastric content (5.6 mg/L), brain (122 mg/kg), fat (99 mg/kg), liver (44 mg/kg), lung (20 mg/kg), and kidney (15 mg/kg). A study of the storage stability of DCM was carried out on these samples. Ethanol production was measured in some organs. The results are discussed in light of the rarity of existing literature.