The study of co-morbid conditions in adults with allergic rhinitis, from Mumbai, Maharashtra, India and their comparison with children

Allergic rhinitis (AR) is an allergen-induced inflammation of the nasal mucosa. Several studies have shown a link not only between AR and asthma but also with other co-morbid conditions. It is important to recognize the onset and existence of these co-morbid conditions, for adequate treatment, prevention of the development of new allergen sensitizations and air-way hypersensitivities. This is a prospective study of co-morbid conditions in adults with AR, from Mumbai, Maharashtra, India and compares them with those in children 23 consecutive children below 6 years (Group 1), 42 children between age of 6 years and 14 years in Group 2 and 57 adults in Group 3 were selected for the symptoms of AR (sneezing, watering and blocked nose), which were currently sufficiently troublesome to require medication. A high association of co-morbid conditions with AR was found. More than 80% suffered from one to three co-morbid conditions each. The most common co-morbid condition was asthma in all the groups. Often asthma and sinusitis was asymptomatic and a high degree of suspicion was needed for diagnosis. Adults had the highest prevalence of sinusitis and allergic conjunctivitis. Prevalence of urticaria was similar in children as well as adults. Studies with larger data samples are needed to confirm these associations.     

Cholangiocarcinoma presenting with severe gastroparesis and pseudoachalasia.

Tumor-associated gastroparesis, though reported in association with various malignancies, is rare in patients with cholangiocarcinoma. We report a 55-year-old woman who presented with dysphagia and recurrent vomiting. Esophagogastroduodenoscopy revealed dilated stomach and excess residue without organic obstruction. 99mTc sulfur colloid solid gastric emptying study, radio-opaque marker gut transit study, and esophageal manometry showed features suggestive of gastroparesis and achalasia cardia; electrogastrography revealed bradygastria. Cholangiocarcinoma was detected on CT scan performed after the patient developed jaundice two months later. The lesion was deemed surgically unresectable. She died four months later.     

Patient‐reported outcomes from SYNERGY,a randomized,double‐blind,multicenter study evaluating combinations of mirabegron and solifenacin compared with monotherapy and placebo in OAB patients

Aims

To evaluate patient‐reported outcomes (PROs) of combinations of solifenacin and mirabegron compared with solifenacin and mirabegron monotherapy and with placebo in patients with overactive bladder (OAB) from the SYNERGY trial.

Methods

Following a 4‐week placebo run‐in, period patients (≥18 years) with OAB were randomized 2:2:1:1:1:1 to receive solifenacin 5 mg + mirabegron 25 mg (combination 5 + 25 mg), solifenacin 5 mg + mirabegron 50 mg, (combination 5 + 50 mg), solifenacin 5 mg, mirabegron 25 mg, mirabegron 50 mg or placebo for 12 weeks, followed by a 2‐week washout period. At each visit, PROs related to quality of life, symptom bother, and treatment satisfaction were assessed, including OAB‐q Symptom Bother score, health‐related quality of life (HRQOL) Total score, treatment satisfaction‐visual analogue scale (TS‐VAS), and patient perception of bladder condition (PPBC) questionnaires.

Results

Overall, 3527 patients were randomized into the study, with 3494 receiving double‐blind treatment. At end of treatment (EoT), both combination groups showed greater improvements in OAB‐q Symptom Bother score compared with the monotherapy groups (nominal P < 0.001). Statistically significant improvements in HRQOL Total scores were observed in the combination groups versus monotherapy groups (P ≤ 0.002). For both combination groups, the OAB‐q Symptom Bother score responder rates at EoT were statistically significantly higher versus mirabegron monotherapy (P < 0.05). The mean adjusted changes from baseline to EoT for PPBC were greater in the combination groups compared with monotherapy groups.

Conclusions

PROs showed that combination therapy provided clear improvements and an additive effect for many HRQOL parameters, including OAB‐q Symptom Bother score, HRQOL Total score, and PPBC.     

Inhibition of Japanese encephalitis virus infection by diethyldithiocarbamate is independent of its antioxidant potential

Diethyldithiocarbamate (DDTC), a low molecular weight dithiol, has been described as an immunomodulator and modifier of diverse biological actions in human and animal models, and has also been shown to be effective in several disease conditions. Therefore, we studied the therapeutic aspect of DDTC in providing inhibition of Japanese encephalitis virus (JEV) infection. DDTC tested at various doses (10-100 micromol/kg) revealed that administration at low concentration (10 micromol/kg; i.p.) on alternate days prolonged the average survival time (AST) of mice infected with lethal dose of JEV (102 LD50, i.c.) and delayed progression of the disease. The low dose also provided > 80% survival in sub-clinical (10(5) LD50, i.c.) JEV infection. Administration of DDTC to JEV-infected mice enhanced the inducible nitric oxide synthase (iNOS) activity in brain and level of serum tumour necrosis factor-alpha (TNF-alpha). We have recently demonstrated the production of nitric oxide (NO) via induction of iNOS activity is meditated by circulating macrophage-derived factor (MDF), which may be responsible for the delayed progression of the disease. DDTC-mediated inhibition of JEV is believed to involve the augmentation of protective role of MDF as evidenced by the observation that pretreatment with anti-MDF antibody significantly decreased the AST of mice and together with the inhibition of iNOS activity. Interestingly, DDTC alone did not stimulate iNOS and TNF-alpha in mock-infected normal mice. These results show that DDTC may have a possible therapeutic role during JEV infection.     

Use of Tunneled-Cuffed Central Catheters in Patients with Cancer: A Single-Center Experience

Background

Effective and reliable venous access is among the cornerstones of modern medical therapy in oncology.

Integrative executive function training in chronic stroke—A case example

Cognitive and functional impairments are common sequelae following stroke, often resulting in significant disabilities that persist years post‐stroke. While the degree of impairments varies with pathology and location of stroke, it is widely understood that executive dysfunction including disturbances of attention, complex information processing, inhibition, reasoning, and flexible thinking underlie a majority of the impairments. Existing rehabilitation approaches predominantly focus on mitigating targeted cognitive deficits (e.g., language disturbance, neglect of one side of the body, memory). Remediation approaches to address executive dysfunction in chronic stages of recovery post‐stroke are limited. The Strategic Memory Advanced Reasoning Training (SMART) that teaches strategies to improve higher order reasoning skills has proven to enhance executive functions, strengthen brain networks and improve participation in daily life activities in adults with traumatic brain injury. The current case example, part of an ongoing larger study, discusses post‐SMART performance of a 57‐year‐old female stroke survivor, who sustained a left middle cerebral artery infarct in July 2015. The participant showed gains in executive functions and participation in leisure pursuits following 10 SMART sessions. These preliminary findings prove feasibility of the training approach and offer promise of neuroplasticity during chronic stages of recovery.     

Utility of flexion–extension radiography for the detection of ligamentous cervical spine injury and its current role in the clearance of the cervical spine

Detecting the presence of injuries to the cervical spine is an important component of the initial assessment of patients sustaining blunt trauma. A small proportion of cervical spine injuries consists of ligamentous disruption. Accurate detection of ligamentous injury is essential as it may result in sequelae including radiculopathy, quadriplegia and death. Flexion–extension (FE) radiography has traditionally been utilised for the detection of ligamentous injury in patients who have been cleared of bony injury. There are controversies surrounding the use of FE for alert patients with neck pain. There are studies that call into question the diagnostic accuracy of FE, the high proportion of inadequate FE images due to muscle spasm and the adverse effects of prolonged cervical collar immobilisation while awaiting FE. Other literature indicates that FE provides no additional diagnostic information following a multi‐detector helical computed tomography. This review evaluates the literature on the utility of FE for the detection of ligamentous injury and explores alternate strategies for clearing the cervical spine of ligamentous injury.     

Hyperbranched PEGmethacrylate linear pDMAEMA block copolymer as an efficient non-viral gene delivery vector

A unique hyperbranched polymeric system with a linear poly-2-dimethylaminoethyl methacrylate (pDMAEMA) block and a hyperbranched polyethylene glycol methyl ether methacrylate (PEGMEMA) and ethylene dimethacrylate (EGDMA) block was designed and synthesized via deactivation enhanced atom transfer radical polymerisation (DE-ATRP) for efficient gene delivery. Using this unique structure, with a linear pDMAEMA block, which efficiently binds to plasmid DNA (pDNA) and hyperbranched polyethylene glycol (PEG) based block as a protective shell, we were able to maintain high transfection levels without sacrificing cellular viability even at high doses. The transfection capability and cytotoxicity of the polymers over a range of pDNA concentration were analysed and the results were compared to commercially available transfection vectors such as polyethylene imine (branched PEI, 25 kDa), partially degraded poly(amido amine)dendrimer (dPAMAM; commercial name: SuperFect(?)) in fibroblasts and adipose tissue derived stem cells (ADSCs).     

Molecular profiling of the “plexinome” in melanoma and pancreatic cancer

Plexins are transmembrane high‐affinity receptors for semaphorins, regulating cell guidance, motility, and invasion. Functional evidences implicate semaphorin signals in cancer progression and metastasis. Yet, it is largely unknown whether plexin genes are genetically altered in human tumors. We performed a comprehensive gene copy analysis and mutational profiling of all nine members of the plexin gene family (plexinome), in melanomas and pancreatic ductal adenocarcinomas (PDACs), which are characterized by high metastatic potential and poor prognosis. Gene copy analysis detected amplification of PLXNA4 in melanomas, whereas copy number losses of multiple plexin genes were seen in PDACs. Somatic mutations were detected in PLXNA4, PLXNB3, and PLXNC1; providing the first evidence that these plexins are mutated in human cancer. Functional assays in cellular models revealed that some of these missense mutations result in loss of plexin function. For instance, c.1613G>A, p.R538H mutation in the extracellular domain of PLXNB3 prevented binding of the ligand Sema5A. Moreover, although PLXNA4 signaling can inhibit tumor cell migration, the mutated c.5206C>T, p.H1736Y allele had lost this activity. Our study is the first systematic analysis of the “plexinome” in human tumors, and indicates that multiple mutated plexins may be involved in cancer progression. Hum Mutat 30,1–8, 2009. © 2009 Wiley‐Liss, Inc.