Adenocarcinoma of the Esophagus in the Young

Introduction

Practitioners have noted a striking increase in the number of young patients under the age of 40 years old who develop esophageal adenocarcinoma. The aim of this study was to characterize the presentation, pathology and therapeutic outcome of these young patients.

Methods

The records of patients who presented to the Foregut Surgical Service at the University of Southern California with esophageal adenocarcinoma between 2000 and 2007 were retrospectively reviewed. The presentation, tumor stage and histology, therapy and outcome of the patients under the age of 40 were compared to those ≥40.

Results

Of the 374 patients reviewed, 20 (5 %) were under the age of 40. There were two patients in their second and 18 in their third decade of life. The youngest patient was 25 years old. A history of gastroesophageal reflux disease or Barrett’s esophagus was less common in patients <40 than in those ≥40; 15 and 5 % compared to 61 and 46 %. Similarly, patients <40 had a significantly longer time interval between the onset of symptoms and the diagnosis of their cancer than those ≥40; 4.5 vs. 2 months, p?=?0.04. They also had a higher prevalence of stage IV disease (30 vs. 6 %, p?=?0.0003), a shorter time to recurrence (9.5 vs.19 month, p?=?0.002), and a poorer median survival (17 vs. 43 month, p?=?0.04).

Conclusion

Esophageal adenocarcinoma in patients <40 years old commonly presents with an advanced stage of the disease and an associated poor survival. This is likely due to a low index of suspicion that dysphagia seen in younger patients is due to a malignancy.     

Listeria meningitis complicating a patient with ulcerative colitis on concomitant infliximab and hydrocortisone

Infliximab, a monoclonal antibody directed against tumour necrosis factor, is an effective therapy for moderate-to-severe ulcerative colitis and Crohn’s disease. Uncommonly, serious opportunistic infections have occurred in patients after infliximab administration. Here, we describe meningitis caused by Listeria monocytogenes developing in a 37-year-old man with ulcerative colitis refractory to intravenous corticosteroids 10 days after receiving his first infusion of infliximab. With the increasing use of tumour necrosis factor-α-neutralizing agents, clinicians should be aware of the risk of opportunistic infections caused by L. monocytogenes in patients with inflammatory bowel disease following infliximab treatment. The half-life of infliximab is 9.5 days; therefore, patients tend to be more susceptible in the immediate period following infusion. Patients receiving anti-TNF therapy should be advised to avoid foods such as soft cheeses and unpasteurized dairy products.     

Cleavage-stage embryo micromanipulation in the clinical setting

Embryo micromanipulation was developed after introduction of microinjection to overcome infertility. Embryo micromanipulation may be performed at any embryo stage from pronuclear to blastocyst. The technique started out as basic and turned out to be increasingly more complex. Embryo micromanipulation at the cleavage-stage includes a wide range of techniques, from opening the zona pellucida in order to improve the chance of implantation, to removing detrimental components from the embryo to enhance embryo development or blastomeres for preimplantation genetic diagnosis and embryo splitting. Evaluating the impact(s) of different micromanipulation techniques on epigenetics of the embryo and considering quality control during these techniques are important issues in this regard. This review aims to discuss the micromanipulation of cleavage-stage embryos in clinical assisted reproductive technology (ART).

Abbreviations: ART: assisted reproductive technology; ICSI: intracytoplasmic sperm injection; IVF: in vitro fertilization; PGD: preimplantation genetic diagnosis; PZD: partial zona dissection; ZP: zona pellucida; SUZI: subzonal insemination; PVS: perivitelline space; AH: assisted hatching; LAH: laserassisted hatching; ZT: zona thinning; UV: ultraviolet; IR: infrared; PCR: polymerase chain reaction; FISH: fluorescent in situ hybridization; NGS: next generation sequencing; QC: quality control; QA: quality assurance     

Preparation and in vivo evaluation of anti-plasmodial properties of artemisinin-loaded PCL–PEG–PCL nanoparticles

Abstract

Purpose: Artemisinin (ART) has anti-inflammatory, antimicrobial, antioxidant, anti-amyloid, and anti-malarial effects, but its application is limited due to its low water solubility and poor oral bioavailability. In this study, the bioavailability, water solubility, and anti-plasmodial property of ART were improved by PCL–PEG–PCL tri-block copolymers.

Methods: The structure of the copolymers was characterized by ¹H NMR, FT-IR, DSC, and GPC techniques. ART was encapsulated within micelles by a single-step nano-precipitation method, leading to the formation of ART-loaded PCL–PEG–PCL micelles. The obtained micelles were characterized by dynamic light scattering (DLS) and atomic force microscopy (AFM). The in vivo anti-plasmodial activity of ART-loaded micelles was measured against Plasmodium berghei infected Swiss albino mice.

Results: The results showed that the zeta potential of ART-loaded micelles was about ?8.37?mV and the average size was 91.87?nm. ART was encapsulated into PCL–PEG–PCL micelles with a loading capacity of 19.33?±?0.015% and encapsulation efficacy of 87.21?±?3.32%. In vivo anti-plasmodial results against P. berghei showed that multiple injections of ART-loaded micelles could prolong the circulation time and increase the therapeutic efficacy of ART.

Conclusion: These results suggested that PCL–PEG–PCL micelles would be a potential carrier for ART for the treatment of malaria.     

Renal protective effect of N-acetylcysteine with stepwise ramping voltage against extracorporeal shock wave lithotripsy-induced renal injury: a prospective randomized trial

International Urology and Nephrology - To evaluate the role of combination of N-acetylcysteine with stepwise ramping voltage in renal protection against the ischemic, vascular and oxidative effects...     

Raloxifene adjunctive therapy for postmenopausal women suffering from chronic schizophrenia: a randomized double-blind and placebo controlled trial

Background

Cumulative evidence from epidemiological, preclinical and clinical studies suggests estrogens may have psychoprotective effects in schizophrenic patients. Selective Estrogen Receptor Modulators could have therapeutic benefits in schizophrenia for both sexes without being hazardous to gynecological tissues or having feminizing effects. Few studies have been conducted regarding the effects of raloxifene on postmenopausal women suffering from schizophrenia. We conducted this placebo-controlled trial to compare the add-on effect of raloxifene to risperidone versus risperidone with placebo.

Methods

This was an 8-week, parallel-group, placebo-controlled trial undertaken at two universities affiliated psychiatric Hospitals in Iran. Forty-six postmenopausal women with the definite diagnosis of schizophrenia were enrolled in the study. Patients received risperidone (6 mg/day in 3 divided doses) combined with either placebo (N = 23) or 120 mg/day of raloxifene (N = 23) for 8 weeks. Patients were assessed by a psychiatrist at baseline and at 2 and 8 weeks after the start of medical therapy. Efficacy was defined as the change from baseline to endpoint in score on Positive and Negative Syndrome Scale (PANSS).

Results

For PANSS scores, the main effect comparing two types of intervention was not significant [F (1, 48) = 1.77, p = 0.18]. For positive subscale scores, there was marginal significant interaction between intervention type and time [F (2, 47) = 2.93, p = 0.06] and there was substantial main effect for time [F (2, 47) = 24.39, p = 0.001] within both groups showing reduction in positive subscale scores across the three time periods. In addition, the main effect comparing two types of intervention was significant [F (1, 48) = 3.78, p = 0.02]. On the other hand, for negative subscale scores, the main effect comparing two types of intervention was not significant [F (1, 48) = 1.43, p = 0.23]. For general subscale scores, the main effect comparing two types of intervention was not significant [F (1, 48) = 0.03, p = 0.86].

Conclusions

According to our findings, raloxifene as an adjunctive treatment to risperidone was only superior in improvement of positive symptoms and it was not effective in treating negative and general psychopathology symptoms.

Trial registration

The trial was registered at the Iranian registry of clinical trials: IRCT201205131556N42     

A double-blind, placebo controlled, randomized trial of riluzole as an adjunct to risperidone for treatment of negative symptoms in patients with chronic schizophrenia

Rationale

Several recent studies have focused on glutamate modulating agents for symptoms relief in schizophrenia, especially negative symptoms which are resistant to conventional therapies.

Objectives

We aimed to assess the efficacy and tolerability of riluzole, an anti-glutamate agent with neuroprotective properties, as an adjunct to risperidone in improving negative symptoms of schizophrenia.

Methods

In this randomized double-blind placebo-controlled parallel-group study, 50 patients with chronic schizophrenia and a score of ≥20 on the negative subscale of positive and negative syndrome scale (PANSS) were enrolled in the active phase of their illness. Participants were equally randomized to receive riluzole (100 mg/day) or placebo in addition to risperidone (up to 6 mg/day) for 8 weeks. Participants were rated by PANSS every 2 weeks. The primary outcome of this study was the difference in the decrease of PANSS negative subscale score from baseline to the study endpoint between the two groups.

Results

By the study endpoint, riluzole-treated patients showed significantly greater improvement in the negative symptoms (P?<?0.001) as well as the PANSS total and general psychopathology subscale scores (P?=?0.001 and P?<?0.001; respectively) compared to the placebo group. Treatment group was the only significant predictor of changes in negative symptom in this trial (β?=??0.56, P?<?0.001). No significant difference was observed between two groups in the frequency of side effects.

Conclusion

These preliminary findings suggest that riluzole may be a safe and effective medication for the treatment of negative symptoms in patients with chronic schizophrenia. Further research and replication of study findings is warranted.

Clinical trial registry name and registration number

Iranian registry of clinical trials www.irct.ir, IRCT201107281556N26