Majority of BBS can be successfully managed with 1-2 consecutive FCSEMS with stent dwell time of 6 months.
Previously, we demonstrated that mice in which the gene for the L-type voltage-gated calcium channel CaV1.3 is deleted (CaV1.3 knockout mice) exhibit an impaired ability to consolidate contextually-conditioned fear. Given that this form of Pavlovian fear conditioning is critically dependent on the basolateral complex of the amygdala (BLA), we were interested in the mechanisms by which CaV1.3 contributes to BLA neurophysiology. In the present study, we used in vitro amygdala slices prepared from CaV1.3 knockout mice and wild-type littermates to explore the role of CaV1.3 in long-term potentiation (LTP) and intrinsic neuronal excitability in the BLA. We found that LTP in the lateral nucleus (LA) of the BLA, induced by high-frequency stimulation of the external capsule, was significantly reduced in CaV1.3 knockout mice. Additionally, we found that BLA principal neurons from CaV1.3 knockout mice were hyperexcitable, exhibiting significant increases in firing rates and decreased interspike intervals in response to prolonged somatic depolarization. This aberrant increase in neuronal excitability appears to be at least in part due to a concomitant reduction in the slow component of the post-burst afterhyperpolarization. Together, these results demonstrate altered neuronal function in the BLA of CaV1.3 knockout mice which may account for the impaired ability of these mice to consolidate contextually-conditioned fear.
Using pharmacological approaches, others have suggested that L-type voltage-gated calcium channels (L-VGCCs) mediate both consolidation and extinction of conditioned fear. In the absence of L-VGCC isoform-specific antagonists, we have begun to investigate the subtype-specific role of LVGCCs in consolidation and extinction of conditioned fear using a molecular genetics approach. Previously, we used this approach to demonstrate that the Ca v 1.3 isoform mediates consolidation, but not extinction, of contextually conditioned fear. Here, we used mice in which the gene for the L-VGCC pore-forming subunit Ca v 1.2 was conditionally deleted in forebrain excitatory neurons (Ca v 1.2 cKO mice) to address the role of Ca v 1.2 in consolidation and extinction of conditioned fear. We demonstrate that Ca v 1.2 cKO mice consolidate and extinguish conditioned fear as well as control littermates. These data suggest that Ca v 1.2 is not critical for these processes and together with our previous data argue against a role for either of the brain-expressed L-VGCCs (Ca v 1.2 or Ca v 1.3) in extinction of conditioned fear. Additionally, we present data demonstrating that the L-VGCC antagonist nifedipine, which has been used in previous conditioned fear extinction studies, impairs locomotion, and induces an aversive state. We further demonstrate that this aversive state can enter into associations with conditioned stimuli that are present at the time that it is experienced, suggesting that previous studies using nifedipine were likely confounded by drug toxicity. Taken together, our genetic and pharmacological data argue against a role for Ca v 1.2 in consolidation of conditioned fear as well as a role for L-VGCCs in extinction of conditioned fear.Pavlovian fear conditioning is a popular paradigm for both the study of associative learning (Fanselow and Poulos 2005) and modeling anxiety disorders (Delgado et al. 2006;Hofmann 2007). In this paradigm, an association between a conditional stimulus (CS) and an aversive unconditional stimulus (US) is acquired through pairing the CS with the US. Learning of this association is identified by the emergence of new responses to the CS, termed conditioned fear responses. The process by which this learning is transformed into a stable long-term memory with the
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, also known as drug-induced hypersensitivity syndrome, is a serious, sometimes lethal, immunological reaction to drug metabolites involving multiple organ systems. Some of the common causative agents of DRESS include allopurinol, minocycline, sulfasalazine, azathioprine, antiepileptic drugs, and hydroxychloroquine. DRESS is often misdiagnosed and challenging to clinically manage due to the disease’s myriad presentations, acute complications, and long-term sequela after initial resolution. We present the case of a 39-year-old female patient that developed type 1 diabetes as a sequela of DRESS. The patient originally presented to the emergency department with three days of fevers and a pruritic erythematous maculopapular rash that began two weeks prior. She had recently started an antibiotic course and had also been on a long-term antiepileptic drug regimen. Following a thorough clinical examination, the patient was diagnosed with DRESS and treated accordingly. Over the next four months, she went on to have multiple hospitalizations with several admissions to the medical intensive care unit. She had numerous complications including significant facial edema, seizures, bacterial pneumonia, sepsis, hypovolemic shock, acute respiratory distress syndrome, diabetic ketoacidosis, nonalcoholic steatohepatitis, liver failure, and recurring DRESS rashes despite treatment with high-dose intravenous steroids and immunosuppressants. During this time, the patient developed a rare form of uncontrolled type 1 diabetes mellitus not explained by autoantibody production or continued high-dose steroid use. Fulminant type 1 diabetes mellitus is a sequela of DRESS that is poorly understood and rarely reported. When it occurs, it significantly and negatively affects patient prognosis and requires careful monitoring to assure proper glycemic control.
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