Subtle case of dapsone-induced methaemoglobinaemia.

Methaemoglobinaemia is a rare disease that is typically caused by a medication or other exogenous agent, with dapsone being the most common. It occurs when the concentration of methaemoglobin rises via ferrous haeme irons becoming oxidised to the ferric state, which shifts the oxygen dissociation curve to the left. The net result of an elevated methaemoglobin concentration is functional anaemia and impaired oxygen delivery to tissues. At lower blood levels, this can cause symptoms such as cyanosis, lethargy, headache and fatigue, whereas at higher levels it can be fatal. Here we discuss a subtle case of dapsone-induced methaemoglobinaemia presenting as subacute mental status changes and apparent hypoxia, thus highlighting the association between methaemoglobinaemia and dapsone. This case demonstrates the importance of thorough medication reconciliation and maintaining a broad differential diagnosis, while also recognising the significance of conflicting data and their implications for the workup.

Lupus-associated protein losing enteropathy (LUPLE) complicated by a hypercoagulable state and successfully treated with belimumab.

Protein-losing enteropathy (PLE) is a condition characterized by gut mucosal injury that typically manifests with edema and hypoalbuminemia due to protein loss in the GI tract. We present a rare case of lupus-associated PLE (LUPLE) manifested by profound edema, diarrhea, and thrombotic complications. Through our case report, we discuss the typical clinical presentation, diagnostic studies available, and treatment options for these patients. Our patient's clinical picture and laboratory markers improved with the initiation of corticosteroids and belimumab, which is a novel treatment regimen for LUPLE. Moreover, our patient was found to have a clinically significant hypercoagulable state that was ultimately attributed to PLE in the setting of systemic lupus erythematosus (SLE). We highlight the increased thrombotic risk in these patients and the subsequent management implications with regard to anticoagulation. Gastroenterologists are likely to be involved in the care of these patients, and may be the first to recognize the constellation of findings in PLE, leading to potentially very effective treatment.

Esophageal Adenocarcinoma in Patients Younger than 40 Years: A Two-Decade Experience at a Public and Private Hospital.

Esophageal adenocarcinoma is typically observed in the older non-Hispanic white population. Changing demographics are altering the epidemiology of the disease. The aim of this study is to review the presentation and outcomes of esophageal adenocarcinoma patients <40 years old at our institution. A retrospective review was performed of patients diagnosed with esophageal adenocarcinoma between 1990 and 2013. Demographics, presentation, and outcomes were compared in those <40 years old and those ≥40 years old. There were 772 total cases with 42 (5%) <40 years old consisting of 37 (88.1%) males, five females and median age of diagnosis of 35 (interquartile range: 31-38). The two most common ethnicities were White non-Hispanic/Latino in 19 (45.2%), Hispanic /Latino in 18 (42.9%). Compared with patients 40 years and older, the younger group had more Hispanic/Latinos than the older group (43% vs 17%, P < 0.001), more frequently presented with stage IV disease (50% vs 29%) and had a shorter median survival. In conclusion, younger patients tend to present at a much later stage than the older counterparts, which may be due to a delay in diagnosis as well as more aggressive biology. Esophageal adenocarcinoma seems to be increasing in the Hispanic/Latino population.

Overinhibition of corticostriatal activity following prenatal cocaine exposure.

OBJECTIVE: Prenatal cocaine exposure (PCE) can cause persistent neuropsychological and motor abnormalities in affected children, but the physiological consequences of PCE remain unclear. Conclusions drawn from clinical studies can sometimes be confounded by polysubstance abuse and nutritional deprivation. However, existing observations suggest that cocaine exposure in utero, as in adults, increases synaptic dopamine and promotes enduring dopamine-dependent plasticity at striatal synapses, altering behaviors and basal ganglia function. METHODS: We used a combination of behavioral measures, electrophysiology, optical imaging, and biochemical and electrochemical recordings to examine corticostriatal activity in adolescent mice exposed to cocaine in utero. RESULTS: We show that PCE caused abnormal dopamine-dependent behaviors, including heightened excitation following stress and blunted locomotor augmentation after repeated treatment with amphetamine. These abnormal behaviors were consistent with abnormal γ-aminobutyric acid (GABA) interneuron function, which promoted a reversible depression in corticostriatal activity. PCE hyperpolarized and reduced tonic GABA currents in both fast-spiking and persistent low-threshold spiking type GABA interneurons to increase tonic inhibition at GABAB receptors on presynaptic corticostriatal terminals. Although D2 receptors paradoxically increased glutamate release following PCE, normal corticostriatal modulation by dopamine was reestablished with a GABAA receptor antagonist. INTERPRETATION: The dynamic alterations at corticostriatal synapses that occur in response to PCE parallel the reported effects of repeated psychostimulants in mature animals, but differ in being specifically generated through GABAergic mechanisms. Our results indicate approaches that normalize GABA and D2 receptor-dependent synaptic plasticity may be useful for treating the behavioral effects of PCE and other developmental disorders that are generated through abnormal GABAergic signaling.