Detection of Cross-Correlation between Gravitational Lensing and γ Rays.

In recent years, many γ-ray sources have been identified, yet the unresolved component hosts valuable information on the faintest emission. In order to extract it, a cross-correlation with gravitational tracers of matter in the Universe has been shown to be a promising tool. We report here the first identification of a cross-correlation signal between γ rays and the distribution of mass in the Universe probed by weak gravitational lensing. We use data from the Dark Energy Survey Y1 weak lensing data and the Fermi Large Area Telescope 9-yr γ-ray data, obtaining a signal-to-noise ratio of 5.3. The signal is mostly localized at small angular scales and high γ-ray energies, with a hint of correlation at extended separation. Blazar emission is likely the origin of the small-scale effect. We investigate implications of the large-scale component in terms of astrophysical sources and particle dark matter emission.

Modified irinotecan and infusional 5-fluorouracil (mFOLFIRI) in patients with refractory advanced pancreas cancer (APC): a single-institution experience.

Pancreatic adenocarcinoma is the fourth leading cause of cancer death. Recently, MM-398 (nanoliposomal irinotecan) was shown to be associated with significant improvement in outcome measures with acceptable toxicities when combined with 5-fluorouracil (5-FU)/leucovorin (LV) compared to 5-FU/LV alone in patients failing one line of gemcitabine-based therapy. There is a paucity of data evaluating the role of irinotecan in combination with 5FU in advanced pancreas cancer (APC). We performed a retrospective analysis of all patients who received mFOLFIRI (minus bolus 5FU and LV). All patients with metastatic disease who had failed at least one line of gemcitabine-based therapy prior to receiving mFOLFIRI were included in this study. Descriptive statistics were used to assess the continuous variables and adverse events (AEs), and Kaplan-Meier methods were used to calculate the median progression-free survival (PFS) and overall survival (OS). Forty patients were included in this analysis. Patients received 1-5 lines of prior therapy (25 % with more than 3 lines of prior therapy). The mean age at diagnosis was 60, and 98 % had ECOG of 1. The mean CA 19-9 at the start of therapy was 33,169 U/ml. The median PFS was 2.59 months [95 % confidence interval (CI) (1.90, 3.54)], and OS was 4.75 months [95 % CI (3.14, 8.98)]. The most common AEs included fatigue (98 %), neuropathy (83 %), anorexia (68 %), nausea (60 %) and constipation (55 %). Grade 3 toxicities included fatigue (13 %) and rash (3 %). There were no observed grade 4 toxicities. In this single-institution retrospective analysis, mFOLFIRI was found to be both tolerable and relatively effective in a heavily pretreated patient population with APC. Future prospective studies should consider evaluating the role of mFOLFIRI in refractory APC.

Hemodialysis clearance of glyphosate following a life-threatening ingestion of glyphosate-surfactant herbicide.

CONTEXT: Ingestion of glyphosate-surfactant herbicides (GlySH) can result in acute kidney injury, electrolyte abnormalities, acidosis, cardiovascular collapse, and death. In severe toxicity, the use of hemodialysis is reported, but largely unsupported by kinetic analysis. We report the dialysis clearance of glyphosate following a suicidal ingestion of a glyphosate-containing herbicide. CASE DETAILS: A 62-year-old man was brought to the emergency department (ED) 8.5 h after drinking a bottle of commercial herbicide containing a 41% solution of glyphosate isopropylamine, in polyoxyethyleneamine (POEA) surfactant and water. He was bradycardic and obtunded with respiratory depression necessitating intubation and mechanical ventilation. Initial laboratory results were significant for the following: pH, 7.11; PCO2, 64 mmHg; PO2, 48 mmHg; potassium, 7.8 mEq/L; Cr 3.3, mg/dL; bicarbonate, 22 mEq/L; anion gap, 18 mEq/L; and lactate, 7.5 mmol/L. Acidosis and hyperkalemia persisted despite ventilation and fluid resuscitation. The patient underwent hemodialysis 16 h post ingestion, after which he demonstrated resolution of acidosis and hyperkalemia, and improvement in clinical status. Serum glyphosate concentrations were drawn prior to, during, and after hemodialysis. The extraction ratio and hemodialysis clearance were calculated to be 91.8% and 97.5 mL/min, respectively. DISCUSSION: We demonstrate the successful clearance of glyphosate using hemodialysis, with corresponding clinical improvement in a patient with several poor prognostic factors (advanced age, large volume ingested, and impaired consciousness). The effects of hemodialysis on the surfactant compound are unknown. Hemodialysis can be considered when severe acidosis and acute kidney injury complicate ingestion of glyphosate-containing products.

Effects of duration of treatment and dosage of eicosapentaenoic acid and stearidonic acid on red blood cell eicosapentaenoic acid content.

OBJECTIVE: The purpose of this randomized, controlled, parallel group study was to characterize the relationships between dosages of stearidonic acid (SDA) and eicosapentaenoic acid (EPA), and incorporation of EPA into red blood cell (RBC) membranes over time. METHODS: Healthy subjects (n=131) received capsules with placebo (safflower oil), SDA (0.43, 1.3, 2.6, or 5.2 g/d) or EPA (0.44, 1.3, or 2.7 g/d) for 12 weeks. RBC fatty acids were analyzed biweekly. RESULTS: RBC %EPA increased in all EPA and SDA groups (p<0.02 vs. control) except the 0.43 g/d SDA group (p=0.187). For theoretical intakes of EPA of 0.25, 0.5, and 0.89 g/d, the amounts of SDA needed to achieve equivalent RBC EPA enrichment were 0.61, 1.89, and 5.32 g/d (conversion efficiencies of 41%, 26%, and 17%), respectively. CONCLUSIONS: SDA increased RBC %EPA in a dosage and time-dependent manner at intakes as low as 1.3 g/d.

Biopharmaceuticals derived from genetically modified plants.

Modern biotechnology has resulted in a resurgence of interest in the production of new therapeutic agents using botanical sources. With nearly 500 biotechnology products approved or in development globally, and with production capacity limited, the need for efficient means of therapeutic protein production is apparent. Through genetic engineering, plants can now be used to produce pharmacologically active proteins, including mammalian antibodies, blood product substitutes, vaccines, hormones, cytokines, and a variety of other therapeutic agents. Efficient biopharmaceutical production in plants involves the proper selection of host plant and gene expression system, including a decision as to whether a food crop or a non-food crop is more appropriate. Product safety issues relevant to patients, pharmaceutical workers, and the general public must be addressed, and proper regulation and regulatory oversight must be in place prior to commercial plant-based biopharmaceutical production. Plant production of pharmaceuticals holds great potential, and may become an important production system for a variety of new biopharmaceutical products.

Acute endogenous endophthalmitis due to Bartonella henselae.

A 45-year-old man presented with progressively worsening vitreitis of 1 week's duration. Treatment for cat-scratch disease 3 years prior to presentation and persistent vitreitis led to vitrectomy, and analysis of the vitrectomy specimen revealed inflammatory cells and necrotic debris; polymerase-chain-reaction analysis of the vitreous fluid sample, done by use of a novel heminested protocol, demonstrated the presence of Bartonella henselae DNA. Treatment with doxycycline led to improvement in the intraocular inflammation but resulted in a poor visual outcome.

Tissue plasminogen activator to treat impending pupillary block glaucoma in patients with acute fibrinous HLA-B27 positive iridocyclitis.

PURPOSE: To report the use of intracameral tissue plasminogen activator to dissolve fibrinous membranes and break posterior synechiae in patients with acute HLA-B27-positive iridocyclitis with impending pupillary block. METHODS: Two patients with severe acute fibrinous iridocyclitis and seclusio pupillae were identified. Because of the concern of impending pupillary block, intracameral tissue plasminogen activator (12.5 microg in 0.1 ml, Activase; Genentech, Inc, South San Francisco, California) was injected with a 25-gauge needle through the corneal limbus. RESULTS: Both patients showed complete dissolution of fibrin with disruption of posterior synechiae. There were no adverse events after injection. Neither patient required further invasive intervention, and both fully recovered with medical management. CONCLUSIONS: Intracameral tissue plasminogen activator is a safe and effective agent for patients with severe acute iridocyclitis and pupillary seclusion. Patients with clinical signs suggestive of impending pupillary block glaucoma may be considered for tissue plasminogen activator injection to avoid the possible need for emergency surgical iridectomy and synechiolysis.

Ocular complications of topical, peri-ocular, and systemic corticosteroids.

Topical ophthalmic, oral, and intravenous corticosteroids have long been associated with ocular side effects. Recent data suggest that inhaled corticosteroids are also associated with the development of cataract and increased intraocular pressure. Thus far, nasally administered steroids have not been associated with the same effects. Local injection of steroids, even at sites far from the eye, have been associated with the development of cataract, glaucoma, and even retinal and choroidal emboli. Any physician prescribing corticosteroids should be aware of these potential ocular side effects and should advise patients accordingly.

Ciliary body melanocytoma with anterior segment pigment dispersion and elevated intraocular pressure.

PURPOSE: To discuss a case in which melanocytoma of the ciliary body presented with widespread pigment dispersion and elevated intraocular pressure (IOP). METHODS: A 64-year old woman presented with increased IOP and persistent anterior segment inflammation in her right eye. She had undergone a trabeculectomy for uncontrolled IOP before presentation. Slit-lamp examination, gonioscopy, and ultrasound biomicroscopy revealed a ciliary body mass with extension into the subconjunctiva in addition to widespread pigmentary dispersion in the anterior segment. Enucleation of the right eye was performed for histopathologic evaluation, as a diagnosis of ciliary body melanoma was made on clinical examination. RESULTS: Histopathologic findings were diagnostic of a melanocytoma of the ciliary body with necrosis and focal malignant transformation with extension of melanocytoma cells and melanophages into the subconjunctival space, trabecular meshwork, and anterior chamber angle. CONCLUSION: Melanocytoma of the ciliary body is a rare intraocular tumor that may present with pigment dispersion and secondary elevated IOP. Careful examination of the anterior segment is imperative in such cases.

Ocular manifestations of Whipple disease: an atypical presentation.

A 62-year-old man developed bilateral granulomatous iridocyclitis after uncomplicated cataract surgery. On ophthalmic examination, we found moderate inflammation in the anterior chamber and vitreous, with granular crystalline deposits on the iris, intraocular lens, and capsular bag. Biopsy of the lens capsule and vitreous revealed periodic acid-Schiff-positive, diastase-resistant bacilli consistent with Tropheryma whippelii. Electron microscopy and polymerase chain reaction confirmed the diagnosis of Whipple disease. A jejunal biopsy specimen also revealed T whippelii. Treatment with trimethoprim-sulfamethoxazole, cefixime, rifampin, and doxycycline resulted in improvement of systemic symptoms, but intraocular inflammation persisted. Intraocular inflammation was eventually reduced with the intravenous administration of ceftriaxone sodium.