Topical anaesthesia and decongestion in rhinology.

Topical anaesthesia and decongestion of the sinonasal mucosa are used commonly in rhinology practice to facilitate nasal endoscopy, as well as debridement and biopsies. Topical agents used for sinonasal anaesthesia include lignocaine, tetracaine and cocaine. Unlike lignocaine and tetracaine, cocaine also has a decongestant effect. Phenylephrine, oxymetazoline, xylometazoline or adrenaline are usually added to lignocaine and tetracaine to provide decongestion. Several studies have been performed seeking to identify the optimal nasal preparation for nasal endoscopy in the clinic setting. However, there remains no clear consensus in the literature resulting in ongoing wide variation between anaesthetic-decongestant preparations used in clinical practice. Indeed, some authors have argued that no anaesthetic is required at all for flexible nasendoscopy despite the apparent consensus that nasal instrumentation is generally uncomfortable, inferred by the persistence of ongoing research in this area. This review provides a practical summary of local anaesthetic and decongestant pharmacology as it relates to rhinologic practice and summarises the literature to date, with the goal of identifying current gaps in the literature and guiding future research efforts.

Fatal COVID-19 in a neonate after probable late intrauterine transmission.

We report the case of a 35-week gestation infant girl born by emergent cesarean section for fetal distress in a woman with recent coronavirus disease 2019 (COVID-19). Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using polymerase chain reaction (PCR) on the infant at 24 and 48 hours of life were negative. However, at 72 hours of life, the infant's respiratory status worsened, and a repeat SARS-CoV-2 PCR was positive. The infant developed leukopenia, thrombocytopenia, and progressive respiratory failure, and died on the ninth day of life. Pathologic examination of the placenta revealed findings consistent with COVID-19 placentitis, and SARS-CoV-2 RNA staining was positive, suggesting intrauterine transmission of the infection.

Ensemble asteroseismology of solar-type stars with the NASA Kepler mission.

In addition to its search for extrasolar planets, the NASA Kepler mission provides exquisite data on stellar oscillations. We report the detections of oscillations in 500 solar-type stars in the Kepler field of view, an ensemble that is large enough to allow statistical studies of intrinsic stellar properties (such as mass, radius, and age) and to test theories of stellar evolution. We find that the distribution of observed masses of these stars shows intriguing differences to predictions from models of synthetic stellar populations in the Galaxy.

Incorporation of a laminin-derived peptide (SIKVAV) on polymer-modified adenovirus permits tumor-specific targeting via alpha6-integrins.

Effective gene therapy for disseminated metastatic cancer is currently impossible because of poor delivery of vector to target sites. Modification of viral vectors to target advanced cancer has long been a challenge. In this study, we aimed to redirect adenovirus tropism to infect prostate cancer cells via alpha6beta1 integrins, whose expression is upregulated during prostate cancer progression. To ablate normal mechanisms of infection and provide a framework for attachment of targeting ligands, viruses were non-genetically modified with pHPMA-ONp polymer. Addition of polymer-coated virus to prostate cells showed significantly reduced transgene expression compared with unmodified virus. To restore infectivity, an alpha6-integrin binding peptide (-SIKVAV-) derived from laminin was incorporated onto the surface of the polymer-coated viruses. Photon correlation spectroscopic analysis revealed a small increase in the mean diameter of the particles following retargeting. Addition of -SIKVAV- peptide restored virus infectivity of PC-3 cells in a ligand concentration-dependent manner that was significantly improved following removal of unincorporated polymer and peptide. Competition assays using cells preincubated with Ad5 fiber protein or free -SIKVAV- peptide confirmed that entry of retargeted viruses was mediated via the incorporated ligand. Application of retargeted viruses to a panel of human cell lines revealed varying levels of transduction efficiency. Flow cytometric analysis of cells using anti-alpha6 integrin and anti-beta1 integrin antibodies demonstrated that for prostate cells, greater transduction efficiency correlated with higher levels of expression of both integrin subunits. Furthermore with the exception of LNCaP cells, increased alpha6beta1 integrin expression correlated with advanced disease. Intravenous administration of retargeted viruses to tumor-bearing mice resulted in slower plasma clearance and greatly reduced liver tropism, and hence toxicity compared with unmodified virus, while maintaining reporter gene expression in the tumor. The data suggest that YESIKVAVS-retargeted viruses have potential for systemic delivery for the treatment of metastatic disease.

Extended plasma circulation time and decreased toxicity of polymer-coated adenovirus.

Systemic delivery of adenoviral vectors is a major goal in cancer gene therapy, but is currently prohibited by rapid hepatic uptake of virus following intravenous injection with levels of viable virus in the murine plasma typically falling to less than 0.1% after 30 min. We have used a surface-masking technique based on multivalent copolymers of poly(N-(2-hydroxypropyl)methacrylamide) to ablate all pathways of receptor-mediated infection, combined with dose modulation to achieve partial saturation of nonspecific uptake pathways. Polymer coating gave at least 100-fold decreased hepatic transgene expression at all doses and even high doses of coated virus (pc-virus) showed no weight loss or stimulation of serum transaminases. Low doses of virus and pc-virus (10(9) viral particles (vp)/mouse) were mainly captured by the liver (assessed by quantitative PCR), although higher doses led to greater fractional persistence in the plasma (measured after 30 min). Coated virus at a dose of 6 x 10(11) vp/mouse showed nearly 50% plasma circulation, representing a 3.5-fold greater area under the concentration-time curve (0-30 min) compared to unmodified virus. Such an increase in the bioavailability of adenovirus, coupled with substantial decreases in toxicity and unwanted transgene expression is an important step towards producing systemically available tumour-targeted viruses.

Arterio-esophageal communication from a ruptured aberrant right subclavian artery aneurysm. CT diagnosis.

We report the computed tomography (CT) findings of an arterio-esophageal communication from an aberrant right subclavian artery aneurysm which had eroded into the esophagus. Pathologic correlation is provided. To our knowledge, this is the first CT demonstration of an aberrant right subclavian aneurysm causing a communication to the esophagus reported in the literature. Previously, one CT case of a left aberrant subclavian artery aneurysm that had ruptured into the esophagus, had been described. The characteristic location of the aberrant vessel with aneurysmal dilation and the presence of abnormal air identified within the wall of the aneurysm on CT, helped establish the diagnosis antemortem.

Use of In-111 pentetreotide scintigraphy in the diagnosis of a midgut carcinoid causing Cushing's syndrome.

A 57-year-old man presented with clinical features of hypercortisolism and was diagnosed with ACTH-dependent Cushing's syndrome. Biochemical testing showed partial suppression of urinary free cortisol with high dose dexamethasone. Initial computed tomography (CT) of the chest and abdomen, and magnetic resonance imaging of the pituitary were negative. In-111 pentetreotide scintigraphy with single photon emission computerized tomography revealed two 'hot' lesions in the abdomen which were then confirmed by subsequent directed thin-slice abdominal CT and small bowel barium study. At surgery, two segments of ileum, adjoining mesentery and lymph nodes were resected. Histopathology was consistent with a malignant carcinoid tumor of the ileum which stained intensely for ACTH. Plasma ACTH, and serum and urinary cortisol normalized postoperatively. To our knowledge, this is the first reported case of ileal carcinoid tumor causing Cushing's syndrome with premortem diagnosis. Another unique feature of this case is that In-111 pentetreotide scan provided the decisive clue to localization of the tumor.

Hantavirus pulmonary syndrome in Wisconsin.

In the spring of 1993 an outbreak of a new illness caused by a new pathogen was identified in the southwestern United States. This infection struck relatively young, healthy individuals, was characterized by fever, myalgias, respiratory failure, and a high mortality rate. This illness was caused by a new hantavirus and has been termed hantavirus pulmonary syndrome (HPS). The virus is carried by rodents, shed in saliva, urine, and feces. Human infection occurs through inhalation of aerosolized virus. The clinical syndrome has many non-specific signs and symptoms, but does follow a typical course with characteristic laboratory and radiographic findings. Early recognition of this infection is important so maximal supportive care can be initiated. We report the first documented case of hantavirus pulmonary syndrome in Wisconsin and Illinois.