Fatal hepatitis B reactivation in a patient receiving chemoradiation for cervical cancer.

INTRODUCTION: Hepatitis B virus (HBV) infection remains a global public health threat, with approximately 257 million people suffering from chronic HBV infection worldwide in 2015. HBV reactivation is a known complication of immunosuppressive therapy in people suffering with chronic HBV. Medications commonly associated with HBV reactivation include B-cell depleting agents and anthracycline derivatives. There have been very few documented cases of chemoradiation inducing HBV reactivation among scientific literature. CASE REPORT: A 44-year-old woman with chronic HBV infection and [FIGO] stage IIIB cervical cancer developed marked transaminitis and increased HBV viral load after receiving treatment with three doses of cisplatin and one dose of carboplatin with concurrent radiation for cervical cancer.Management and outcome: The patient was admitted for acute liver failure and quickly developed encephalopathy, with treatment complicated by coagulopathy, hypoglycemia, and metabolic acidosis. The patient remained unresponsive to maximal therapeutic efforts and was mechanically ventilated for airway protection. She subsequently died after experiencing ventricular tachycardia followed by asystole. DISCUSSION: There are currently no standardized guidelines for the screening of HBV infection or prophylaxis treatment algorithm for patients undergoing chemoradiation. When initiating treatment with immunosuppressive therapy, it is important to screen all patients for chronic HBV infection and to work with an interdisciplinary team of oncologists, hepatologists, and pharmacists to initiate prophylactic antiviral therapy and closely monitor to minimize the risk of HBV reactivation.

Howell-Jolly bodies on peripheral smear leading to the diagnosis of congenital hyposplenism in a patient with septic shock.

We present a case of isolated congenital hyposplenism that was discovered after the peripheral smear revealed Howell-Jolly bodies. This case serves as the basis for a review of hyposplenism for the general practitioner.

Bone marrow infiltration as the initial presentation of gastric signet ring cell adenocarcinoma.

This case report describes a 52-year-old African American man who initially presented with worsening back pain. The patient was found to have lytic lucencies in the T5 and T9 vertebral bodies and a subsequent bone marrow biopsy revealed an extensive infiltrate of signet ring cells. These findings prompted a workup for a gastrointestinal malignancy, and upper endoscopy revealed a mass in the gastric pylorus. A biopsy of this mass was positive for signet ring cell adenocarcinoma. This case is significant for two reasons. First, it highlights the importance of a broad differential diagnosis when approaching a patient with lytic bone lesions. Second, bone marrow involvement is more common in patients with diffuse type gastric cancer and occurs in particularly young patients. The increasing incidence of diffuse type gastric adenocarcinoma means bone marrow metastases will likely play a greater role in the presentation and management of gastric cancer.

Protein kinase C acts as a molecular detector of firing patterns to mediate sensory gating in Aplysia.

Habituation of a behavioral response to a repetitive stimulus enables animals to ignore irrelevant stimuli and focus on behaviorally important events. In Aplysia, habituation is mediated by rapid depression of sensory synapses, which could leave an animal unresponsive to important repetitive stimuli, making it vulnerable to injury. We identified a form of plasticity that prevents synaptic depression depending on the precise stimulus strength. Burst-dependent protection from depression is initiated by trains of 2-4 action potentials and is distinct from previously described forms of synaptic enhancement. The blockade of depression is mediated by presynaptic Ca2+ influx and protein kinase C (PKC) and requires localization of PKC via a PDZ domain interaction with Aplysia PICK1. During protection from depression, PKC acts as a highly sensitive detector of the precise pattern of sensory neuron firing. Behaviorally, burst-dependent protection reduces habituation, enabling animals to maintain responsiveness to stimuli that are functionally important.

Serotonin receptor antagonists discriminate between PKA- and PKC-mediated plasticity in aplysia sensory neurons.

Highly selective serotonin (5-hydroxytryptamine, 5-HT) receptor antagonists developed for mammals are ineffective in Aplysia due to the evolutionary divergence of neurotransmitter receptors and because the higher ionic strength of physiological saline for marine invertebrates reduces antagonist affinity. It has therefore been difficult to identify antagonists that specifically block individual signaling cascades initiated by 5-HT. We studied two broad-spectrum 5-HT receptor antagonists that have been characterized biochemically in Aplysia CNS: methiothepin and spiperone. Methiothepin is highly effective in inhibiting adenylyl cyclase (AC)-coupled 5-HT receptors in Aplysia. Spiperone, which blocks phospholipase C (PLC)-coupled 5-HT receptors in mammals, does not block AC-coupled 5-HT receptors in Aplysia. In electrophysiological studies, we explored whether methiothepin and spiperone can be used in parallel to distinguish between the AC-cAMP and PLC-protein kinase C (PKC) modulatory cascades that are initiated by 5-HT. 5-HT-induced broadening of the sensory neuron action potential in the presence of tetraethylammonium/nifedipine, which is mediated by modulation of the S-K+ currents, was used an assay for the AC-cAMP cascade. Spike broadening initiated by 5 microM 5-HT was unaffected by 100 microM spiperone, whereas it was effectively blocked by 100 microM methiothepin. Facilitation of highly depressed sensory neuron-to-motor neuron synapses by 5-HT was used as an assay for the PLC-PKC cascade. Spiperone completely blocked facilitation of highly depressed synapses by 5 microM 5-HT. In contrast, methiothepin produced a modest, nonsignificant, reduction in the facilitation of depressed synapses. Interestingly, these experiments revealed that the PLC-PKC cascade undergoes desensitization during exposure to 5-HT.