Spontaneous resurgence of conditioned fear weeks after successful extinction in brain injured mice.

Mild traumatic brain injury (TBI) is a major risk factor for post-traumatic stress disorder (PTSD), and both disorders share common symptoms and neurobiological defects. Relapse after successful treatment, known as long-term fear resurgence, is common in PTSD patients and a major therapeutic hurdle. We induced a mild focal TBI by controlled cortical impact (CCI) in male C57BL/6 J mice and used fear conditioning to assess PTSD-like behaviors and concomitant alterations in the fear circuitry. We found for the first time that mild TBI, and to a lesser extent sham (craniotomy), mice displayed a spontaneous resurgence of conditioned fear when tested for fear extinction memory recall, despite having effectively acquired and extinguished conditioned fear 6 weeks earlier in the same context. Other characteristic symptoms of PTSD are risk-taking behaviors and cognitive deficits. CCI mice displayed risk-taking behaviors, behavioral inflexibility and reductions in processing speed compared to naïve mice. In conjunction with these changes there were alterations in amygdala morphology 3 months post-trauma, and decreased myelin basic protein density at the primary lesion site and in distant secondary sites such as the hippocampus, thalamus, and amygdala, compared to sham mice. Furthermore, activity-dependent brain-derived neurotrophic factor (BDNF) transcripts were decreased in the prefrontal cortex, a key region for fear extinction consolidation, following fear extinction training in both TBI and, to a lesser extent, sham mice. This study shows for the first time that a mild brain injury can generate a spontaneous resurgence of conditioned fear associated with defective BDNF signalling in the prefrontal cortex, PTSD-like behaviors, and have enduring effects on the brain.

[Infantile bullous pemphigoid]. / Pemphigoïde bulleuse du nourrisson.

BACKGROUND: Bullous pemphigoid (BP) is a form of autoimmune bullous disease commonly seen in adults but rare amongst children. Only a few cases have been described in children after vaccination. This article reports a new case of BP that occurred in an infant after a first vaccination. PATIENTS AND METHODS: A 3-month-old girl presented a bullous eruption 2 weeks after a first injection of Infanrix Quinta(®) and Prevenar(®). The eruption began on her palms and soles. It was associated with urticaria-like lesions on her thighs, chest and abdomen. A histological skin examination and direct immunofluorescence showed dermal-epidermal cleavage and IgG and C3 deposits in the epidermal basement membrane zone, which are typical features of BP. No antibodies against basement membrane were seen. Clinical remission was observed after 5 weeks of treatment with dermal-corticosteroids. Resumption of the vaccination schedule did not induce any recurrence of the disease. DISCUSSION: The clinical presentation of BP amongst children differs from that seen in adults, notably in terms of the predominance of palmoplantar lesions in children aged less than 1 year. In addition, lesions on mucous membrane are more frequently reported amongst older children. Histological findings are similar in all age groups. The outbreak of BP due to a vaccinal antigen appears hypothetical. However, continuation of the vaccination schedule did not induce any recurrence. Moreover, it is a rare disease amongst children despite the frequency of vaccinations in this population. CONCLUSION: Childhood BP is a diagnosis that should be considered in any case of bullous eruption, in particular if the palms and soles are affected. It is a benign disease that resolves in less than a year under treatment. The current data do not incriminate vaccines in the outbreak of childhood BP and suggest that continuation of vaccination is not contraindicated.

[CRP in the management of bacterial infections in emergency]. / Utilité du dosage de la CRP pour la prise en charge des infections bactériennes aux urgences.

OBJECTIVES: To assess the interest of measuring CRP in emergency for diagnosing bacterial infections and making decisions about antibiotics and to compare its practical usefulness with clinicians' conclusions. METHODS: Systematic CRP measurements in 80 consecutive patients admitted to emergency ward with possible bacterial infection. RESULTS: were not transmitted to the physician in charge. Patients' files were analyzed retrospectively in two phases. In phase 1, two senior physicians assessed the diagnosis and need for antibiotics on the basis of the admission (emergency unit) files. In phase 2, a panel of experts examined the complete files (including discharge notes) to determine the likelihood of infection (obvious or probable, unlikely or excluded) and appropriateness of emergency antibiotics. Their recommendations were used as the standard, against which the usefulness of the laboratory indicators (including CRP) and decisions of the emergency physicians were assessed. ROC curves were used to determine threshold values for CRP and body temperature. We then calculated the sensitivity, positive predictive value and negative predictive value of these cutoffs and compared them with those for the phase 1 clinician recommendations. RESULTS: The study included 76 patients (mean age: 74 years): 28 presented obvious or possible infections and 21 required emergency antibiotic therapy. Mean leukocyte values did not differ between groups. For diagnosis, the threshold value of CRP was 85 mg/L and of body temperature 37.8 degrees C; for prescribing antibiotics, the values were 130 mg/L and 38 degrees C, respectively. The sensitivity, specificity, negative and positive predictive values of CRP were, respectively, 79, 81, 76, and 83% for diagnosis of bacterial infection and 71, 71, 48 and 87% for prescription of an emergency antibiotic. These values were lower than those of clinician's conclusions. CONCLUSION: Because of the variability in the thresholds used in its interpretation, the lack of specificity, and its poor predictive value for treatment decisions, CRP is of little interest in the diagnosis and treatment of patients with bacterial infections in intensive care. The cost generated by this examination is therefore not justified.

Association between chronic urticaria and thyroid autoimmunity: a prospective study involving 99 patients.

BACKGROUND: The association between chronic urticaria and thyroid autoimmunity has been a subject of debate. However, this link was suggested in studies searching thyroid microsomal antibodies (TMA), which are less sensitive and less specific than anti-thyroperoxidase antibodies, moreover these studies did not measure anti-TSH receptor antibodies, nor did they use a control group. As a consequence, the results of these studies are difficult to interpret. OBJECTIVE: The aim of this study was to determine whether chronic urticaria is statistically associated with thyroid autoimmunity. METHODS: In a prospective case-control study, we compared the frequency of thyroid autoantibodies in 45 patients with chronic urticaria and in 30 healthy adult volunteers; we also compared the frequency of chronic urticaria in 32 patients with thyroid diseases with thyroid autoantibodies and in 22 patients with thyroid diseases without thyroid autoantibodies. Thyroid autoantibodies and thyroid hormones were measured in all the subjects; antinuclear antibodies, rheumatoid factors, complement, IgE were assessed and routine laboratory tests were done in patients with chronic urticaria. Fisher's exact statistics were used to test our hypothesis. RESULTS: The frequency of thyroid autoantibodies was significantly higher in patients with chronic urticaria than in healthy controls (26.7%/3.3%; p < 0.01). All the patients with thyroid autoantibodies had thyroid hormone concentrations within the normal limits. The frequency of chronic urticaria was not significantly different (12.5%/9.1%; p = 0.7) in patients with thyroid diseases with or without thyroid antibodies. The rest of the biological investigations revealed only 1 patient with connective tissue disease. CONCLUSION: This study shows a significant association between chronic urticaria and thyroid autoimmunity, and that tests to detect thyroid autoantibodies are relevant in patients with chronic urticaria, whereas extensive laboratory tests are not.

Assessment of qualitative functional parameters of stored red blood cells from donors with sickle cell trait (AS) or with heterozygote (AC) status.

We have compared the storage quality of three groups of 10 red blood cell concentrates of the AA, AS and AC haemoglobin phenotype. The 30 samples were drawn on CPD on day 0, and were centrifuged 6 hours later. Leukocytes were removed on D1 and the samples were kept at +4 degrees C for 42 days in SAG-mannitol. Viability tests were performed using a series of in vitro tests, including: ATP, 2,3-DPG, K+, glucose, lactic acid, pH, osmotic fragility tests and erythrocytic morphology determination. Results demonstrated a good functional quality for AS and AC haemoglobin RBCs. Higher 2,3-DPG levels were found in Hb AS and Hb AC. A lower osmotic fragility in Hb AC and AS RBCs versus Hb AA was observed; no significant difference was found in terms of ATP levels and other parameters. In addition no variation in S and C haemoglobin levels and no sickling were observed. In conclusion, these results indicate an overall good quality for haemoglobin AS and AC RBCs. Further in vivo studies must now be performed in order to confirm the transfusional quality of haemoglobin AS and AC RBCs.

Apparent cooperativity for carbamoylphosphate in Escherichia coli aspartate transcarbamoylase only reflects cooperativity for aspartate.

The reaction catalyzed by Escherichia coli aspartate transcarbamoylase (ATCase) proceeds through an ordered mechanism, in which carbamoylphosphate binds first, followed by aspartate; upon binding of this second substrate, the enzyme undergoes a concerted transition from a low-affinity T state to a high-affinity R state. In various studies, conflicting results were obtained concerning the existence of positive cooperativity for the first substrate, carbamoylphosphate. It is shown here that cooperativity for this substrate is only apparent. Indeed, saturation curves for carbamoylphosphate display sigmoidicity only if the aspartate concentration used is high enough to shift ATCase into the R state. Furthermore, it is shown that succinate, an unreactive aspartate analogue which is able to promote the T-->R conformational transition, also induces the appearance of cooperativity for carbamoylphosphate. Similar results were obtained in the course of continuous-flow-dialysis experiments, which show that the binding of carbamoylphosphate is apparently cooperative only in the presence of a concentration of succinate high enough to shift the enzyme into the R state. Taken together, these data show that the apparent cooperativity for carbamoylphosphate is not an intrinsic property of ATCase, as it only reflects the cooperativity for the second substrate, aspartate, as a consequence of the process of ordered substrate binding.