Hemophagocytic Lymphohistiocytosis Caused by a Severe Epstein-Barr Virus Infection in a Young Patient Presenting With Hiccups.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome characterized by a pathologic immune response in the setting of infection, malignancy, acute illness, or any immunological stimulus. Infection is the most common etiology of HLH. HLH involves aberrant activation of lymphocytes and macrophages with resultant hypercytokinemia due to an inappropriately stimulated and ineffective immune response. Here, we present the case of a previously healthy 19-year-old male presenting with hiccups and scleral icterus, who was found to have HLH due to a severe Epstein-Barr virus infection. Despite a morphologically normal bone marrow biopsy, the patient met the diagnostic criteria for HLH, including a low natural killer cell count and elevated soluble interleukin-2 receptor. Notably, ferritin was severely elevated at 85,810 ng/mL. The patient was treated with an induction course of dexamethasone intravenously for eight weeks. Since HLH can progress into multi-organ failure, timely diagnosis and prompt initiation of treatment are critical. Novel disease-modifying therapies and further clinical trials are warranted to treat this potentially fatal immunological disease with multisystem ramifications.

Incidental Moyamoya Disease in an Elderly Patient Presenting With Acute Ischemic Pontine Stroke.

Moyamoya disease (MMD) is a rare occlusive cerebrovascular disease that is characterized by progressive stenosis of the terminal portion of the internal carotid artery and its main branches with compensatory development of dilated and fragile collateral vasculature at the base of the brain. MMD has a bimodal age distribution commonly affecting children and adults, whereas onset in the elderly population is a rare occurrence. Here, we present a case of a 78-year-old patient of Indonesian descent who was incidentally found to have moyamoya arteriopathy after presenting with acute ischemic stroke in the left pons. The patient underwent diagnostic cerebral angiogram that showed right middle cerebral artery stenosis with pathognomonic collateral moyamoya vessels. The patient was discharged on antiplatelet therapy. We report a rare case of an elderly patient with MMD. The role of medical or surgical management in asymptomatic MMD in elderly patients remains largely unknown.

Incidental Splenic Marginal Zone Lymphoma With Extreme Macrocytosis After Hydroxyurea Use: A Case Report.

Splenic marginal zone lymphoma (SMZL) is a low-grade mature B-cell lymphoma that typically presents in the form of splenomegaly and lymphocytosis. The diagnosis is traditionally made through splenic histology, the presence of circulating villous lymphocytes, or bone marrow biopsy. Its treatment can be in the form of chemotherapy, such as rituximab, or active surveillance. This case presentation discusses a 76-year-old female with a long history of hydroxyurea use for an unknown reason presenting with atypical symptoms requiring bone marrow biopsy to diagnose SMZL. This unique case demonstrates the importance of further research and studies into atypical SMZL presentations and hydroxyurea's potential in precipitating secondary malignancies.

Central Diabetes Insipidus in the Background of Lithium Use: Consider Central Causes Despite Nephrogenic as the Most Common.

BACKGROUND Nephrogenic diabetes insipidus is a well-known adverse effect of lithium use. Albeit rare, there have also been documented cases of central diabetes insipidus (CDI) associated with lithium use. CASE REPORT A 31-year-old woman with a past medical history of bipolar disorder, managed with lithium 300 mg by mouth every day for 3 years, was assessed for a 1-year history of polyuria with accompanying polydipsia. During her initial hospital stay, her estimated urine output was more than 4 L per day. Initial labs showed elevated serum sodium (149 mmol/L; reference range 135-145), elevated serum osmolality (304 mOsm/kg; reference range 275-295), urine osmolality of 99 mOsm/kg (reference range 50-1200), and urine specific gravity (1.005; reference range 1.005-1.030). Lithium was at a subtherapeutic level of 0.05 mEq/L (reference range 0.6-1.2). Magnetic resonance imaging of the brain revealed no abnormalities of the pituitary gland. Two different occasions of desmopressin administration resulted in >50% increase in urine osmolality, confirming the diagnosis of CDI. Common causes of CDI, including trauma, tumors, and familial CDI, were ruled out and chronic lithium use was determined as the most probable cause for the patient's CDI. CONCLUSIONS CDI in the background of chronic lithium use is rarely reported. We present this case to consider CDI as a differential diagnosis when evaluating polyuria and hypernatremia in patients with long-term lithium use. These presentations warrant the consideration of both types of diabetes insipidus in the differential diagnoses.

Pantoprazole-Associated Thrombocytopenia: A Literature Review and Case Report.

Proton-pump inhibitors (PPIs) are commonly utilized in the treatment of upper gastrointestinal bleeds (UGIBs) due to their ability to stabilize blood clot formation. PPIs have been shown to reduce rebleeding after endoscopic hemostasis and reduce signs of bleeding at index endoscopy. While PPIs are well-tolerated and commonly administered to patients suffering from acute UGIBs, significant adverse effects may occur. Patients have reported various mild systemic symptoms during short-term PPI use, including headache, rash, dizziness, nausea, abdominal pain, flatulence, constipation, and diarrhea. In general, serious side effects of PPIs tend to be mild during treatment periods under two weeks; however, as the treatment duration increases, side effects have been observed to increase in frequency and severity. PPI-induced thrombocytopenia is an exceedingly rarely reported adverse reaction that remains largely unstudied due to the dearth of patient cases. This adverse effect continues to be a diagnosis of exclusion, and there are no current evidence-based recommendations to approach this complication. Thrombocytopenia increases the risk of rebleeding and hemodynamic instability, which may be devastating to patients suffering from UGIBs. Here, we present a case of thrombocytopenia that began after the introduction of pantoprazole in the setting of a UGIB. The thrombocytopenia resolved promptly after cessation of the medication. We highlight this case to increase awareness of this rare finding given the lack of recommendations for short-term PPI-induced thrombocytopenia.

Fatal outcome in a Hispanic woman with moyamoya syndrome and Graves' disease.

We describe the case of a young Hispanic female who presented with thyrotoxicosis with seizures and ischemic stroke. She was diagnosed with a rare vasculopathy - moyamoya syndrome. After starting antithyroid therapy, her neurologic symptoms did not improve. Acute neurosurgical intervention had relieved her symptoms in the immediate post-operative period after re-anastomosis surgery. However, 2 post-operative days later, she was found to be in status epilepticus and in hyperthyroid state. She quickly deteriorated clinically and had expired a few days afterward. This is the second case in literature of a fatality in a patient with moyamoya syndrome and Graves' disease. However, unlike the other case report, our patient had undergone successful revascularization surgery. We believe her underlying non-euthyroid state had potentiated her clinical deterioration. Case studies have shown positive correlation between uncontrolled hyperthyroidism and stroke-like symptoms in moyamoya syndrome. Mostly all patients with these two disease processes become symptomatic in marked hyperthyroid states. Thus, it may be either fluctuations in baseline thyroid function or thyrotoxicosis that potentiate otherwise asymptomatic moyamoya vasculopathy. LEARNING POINTS: Awareness of the association between Graves' disease and moyamoya syndrome in younger patients presenting with stroke-like symptoms.Obtaining euthyroid states before undergoing revascularization surgery may protect the patient from perioperative mortality and morbidity.Although moyamoya disease is usually thought to be genetically associated, there are reports that thyroid antibodies may play a role in its pathogenesis and have an autoimmune link.Fluctuations in baseline thyroid function for patients with known Graves' disease may be a potentiating factor in exacerbating moyamoya vasculopathy.

Amelioration of nephropathy with apoA-1 mimetic peptide in apoE-deficient mice.

BACKGROUND: There is mounting evidence that dyslipidaemia may contribute to development and progression of renal disease. For instance, hyperlipidaemia in apolipoprotein E-deficient (apoE(-/-)) mice is associated with glomerular inflammation, mesangial expansion and foam cell formation. ApoA-1 mimetic peptides are potent antioxidant and anti-inflammatory compounds which are highly effective in ameliorating atherosclerosis and inflammation in experimental animals. Given the central role of oxidative stress and inflammation in progression of renal disease, we hypothesized that apoA-1 mimetic peptide, D-4F, may attenuate renal lesions in apoE(-/-) mice. METHODS: Twenty-five-month-old female apoE(-/-) mice were treated with D-4F (300 µg/mL in drinking water) or placebo for 6 weeks. Kidneys were harvested and examined for histological and biochemical characteristics. RESULTS: Compared with the control mice, apoE(-/-) mice showed significant proteinuria, tubulo-interstitial inflammation, mesangial expansion, foam cell formation and up-regulation of oxidative [NAD(P)H oxidase subunits] and inflammatory [NF-κB, MCP-1, PAI-1 and COX-2] pathways. D-4F administration lowered proteinuria, improved renal histology and reversed up-regulation of inflammatory and oxidative pathways with only minimal changes in plasma lipid levels. CONCLUSIONS: The apoE(-/-) mice develop proteinuria and glomerular and tubulo-interstitial injury which are associated with up-regulation of oxidative and inflammatory mediators in the kidney and are ameliorated by the administration of apoA-1 mimetic peptide. These observations point to the role of oxidative stress and inflammation in the pathogenesis of renal disease in hyperlipidaemic animals and perhaps humans.

Differential regulation of hepatic cytochrome P450 monooxygenases in streptozotocin-induced diabetic rats.

The present investigation was carried out to study the expression of major cytochrome P450 (CYP) isozymes in streptozotocin-induced diabetes with concomitant insulin therapy. Male Sprague-Dawley rats were randomly assigned to untreated control, streptozotocin-induced diabetic, insulin-treated groups and monitored for 4 weeks. Uncontrolled hyperglycemia in the early phase of diabetes resulted in differential regulation of cytochrome P450 isozymes. CYP1B1, CYP1A2, heme oxygenase (HO)-2 proteins and CYP1A2-dependent 7-ethoxyresorufin O-deethylase (EROD) activity were upregulated in the hepatic microsomes of diabetic rats. Insulin therapy ameliorated EROD activity and the expression of CYP1A2, CYP1B1 and HO-2 proteins. In addition, CYP2B1 and 2E1 proteins were markedly induced in the diabetic group. Insulin therapy resulted in complete amelioration of CYP2E1 whereas CYP2B1 protein was partially ameliorated. By contrast, CYP2C11 protein was decreased over 99% in the diabetic group and was partially ameliorated by insulin therapy. These results demonstrate widespread alterations in the expression of CYP isozymes in diabetic rats that are ameliorated by insulin therapy.

Expression of catalase and glutathione peroxidase in renal insufficiency.

Chronic renal failure (CRF) is associated with oxidative stress, the precise mechanism of which is yet to be elucidated. The present study was undertaken to investigate in renal insufficiency the expression of catalase and glutathione peroxidase, which play a critical role in antioxidant defense system by catalyzing detoxification of hydrogen peroxide (H2O2) and organic hydroperoxides. Rats were randomly assigned to the CRF (5/6 nephrectomized) and sham-operated control groups and observed for 6 weeks. Renal and thoracic aortic catalase and glutathione peroxidase protein abundance was measured by Western blotting. The enzyme activities in the renal and aortic extracts, hepatic glutathione levels, blood pressure and urinary nitric oxide metabolites (NO(x)) excretion were also measured. Blood pressure and urinary nitric oxide metabolite (NO(x)) excretion were also measured. The CRF group showed a significant down-regulation of both immunodetectable catalase and glutathione peroxidase proteins in the remnant kidney. Catalase activity was also significantly decreased in the remnant kidney whereas glutathione peroxidase activity was not significantly affected. Furthermore, the protein abundance of catalase was unchanged whereas the enzyme activity was significantly decreased in the thoracic aorta of CRF animals compared to the sham-operated controls. By contrast, both the protein abundance and the enzyme activity of glutathione peroxidase were not significantly affected in the aorta of CRF animals compared to the sham-operated controls. This was coupled with marked arterial hypertension, significant reduction of hepatic glutathione levels and urinary NO(x) excretion pointing to increased inactivation and sequestration of NO by superoxide. These events point to the role of impaired antioxidant defense system in the pathogenesis of oxidative stress in CRF.

Lead-induced dysregulation of superoxide dismutases, catalase, glutathione peroxidase, and guanylate cyclase.

Previous studies from this laboratory have demonstrated the presence of oxidative stress and its role in the pathogenesis of lead-induced hypertension. This study was designed to determine whether oxidative stress in animals with lead-induced hypertension is associated with dysregulation of the activities of the main antioxidant enzymes, namely superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). In addition, we aimed to determine the effect of lead on the regulation of guanylate cyclase (GC) expression. Male Sprague-Dawley rats were randomly assigned to control and lead-exposed groups, and immunodetectable Cu/Zn SOD, Mn SOD, CAT, and GPX were determined by immunoblotting in the thoracic aorta. Additionally, the activities of these enzymes were measured in the renal cortex, medulla, and thoracic aorta. Furthermore, immunodetectable GC was determined in the thoracic aorta. In the thoracic aorta, lead exposure resulted in significant upregulation of aortic Cu/Zn SOD activity, while CAT and GPX activity and CuZn SOD, Mn SOD, and CAT protein abundance were unchanged. Conversely, GC protein abundance was decreased in thoracic aorta. In renal cortex and medulla, CAT and Cu/Zn SOD activities were increased, while GPX activity was unchanged. Lead-exposed animals exhibited upregulation of some antioxidant enzyme activities, most likely as a compensatory response to lead exposure. However, other enzymes did not compensate in the face of oxidative stress, suggestive of an antioxidant/oxidant imbalance. These findings, combined with decrease in aortic GC protein abundance, provide further evidence for dysregulation of antioxidant/oxidant balance and hypertension in this model.

Superoxide dismutase, catalase, glutathione peroxidase and NADPH oxidase in lead-induced hypertension.

BACKGROUND: Earlier studies from this laboratory have revealed the presence of oxidative stress and its role in the pathogenesis of lead-induced hypertension (HTN). We have further shown evidence of increased hydroxyl radical (.OH) and superoxide production in lead-treated rats and cultured endothelial cells. This study was designed to determine whether oxidative stress in animals with lead-induced HTN is associated with dysregulation of the main antioxidant enzymes namely superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) or increased superoxide producing enzyme nicotinamide adenine dinucleotide (phosphate) oxidase [NAD(P)H]. METHODS: Male Sprague-Dawley rats were randomly assigned to lead-exposed and control groups. Animals in the lead-exposed group were provided with drinking water containing 100 ppm lead acetate for 12 weeks. The control group was provided with regular drinking water. At the conclusion of the experiment, immunodetectable Cu Zn SOD, Mn SOD, CAT, GPX and gp91 phox subunit of NAD(P)H oxidase were determined by Western analysis in the kidney, brain and left ventricle of control and lead-exposed rats. Subgroups of the study animals were treated with IV infusion (180 micromol/kg/h) of the superoxide trapping agent, tempol, and arterial pressure and urinary nitric oxide (NO) metabolite (NOx) excretion were determined. RESULTS: Lead exposure for 12 weeks resulted in a marked rise in systolic blood pressure, a significant reduction in urinary NOx excretion, a significant increase in kidney and brain Cu, Zn SOD, a significant increase in brain and insignificant increase in kidney and heart gp91 phox. In contrast, Mn SOD, CAT and GPX in the kidney, brain and left ventricle were unchanged. Incubation with lead acetate did not alter SOD activity in vitro. Infusion of tempol significantly lowered arterial pressure and raised urinary NOx excretion in the lead-exposed group (but had no effect in the control group) pointing to increased superoxide production in the lead-exposed animals. CONCLUSION: Animals with lead-induced hypertension exhibited oxidative stress which was associated with mild up-regulation of superoxide-generating enzyme, NAD(P)H oxidase, with no evidence of quantitative SOD, CAT or GPX deficiencies.