Epidermal growth factor regulation of DNA synthesis in human colonic lamina propria lymphocytes

Epidermal growth factor (EGF) is a potent growth factor for many tissues including the gastrointestinal tract. EGF is present in the gut lumen and is absorbed through the mucosa in the developing animals. In addition, EGF has been found to alter the immune system. In this study, we investigated thein vitro effect of EGF on normal colonic lamina propria lymphocyte DNA synthesis and ornithine decarboxylase activity. Human colonic lamina propria lymphocytes were isolated by collagenase-EDTA digestion. The effect of EGF on Con A-stimulated lymphocyte thymidine incorporation was tested. We observed that EGF suppressed DNA synthesis and ornithine decarboxylase (ODC) activity in lamina propria lymphocytes. EGF did not alter the time course of thymidine incorporation into LPL stimulated by the combination of phorbol 12,13-dibutyrate (PDB) and ionomycin. Our data suggest that (1) EGF suppresses DNA synthesis in human colonic lamina propria lymphocytes as well as ODC activity and (2) this inhibition may be mediated through protein kinase C or calcium flux. We postulate that EGF may have a role in modulating the human gut immune system.This work was supported in part by grant CA43280 from the National Institutes of Health.     

Angiotensin-converting enzyme gene polymorphisms and hypertension in occupational noise exposure in Egypt

Background:

The gene–environment interaction in the pathogenesis of hypertension has not been extensively studied in occupational noise.

Objectives:

The aim of this study was to determine the relationship between noise and hypertension in Egyptian workers, the interaction of angiotensin-converting enzyme (ACE) gene polymorphisms as modifiers, and the possible relationship between noise hearing impairment and hypertension.

Methods:

Study subjects were divided into two groups depending on noise exposure level. The control group (n = 161) was exposed to noise intensity <85 dB and the exposed group (n = 217) was exposed to noise intensity ≧85 dB. A polymerase chain reaction was used to differentiate the various genotypes of ACE insertion/deletion (I/D) and ACE G2350A.

Results:

Noise significantly increased the likelihood of hypertension. Carriers of the genotypes AG, GG, and DD were vulnerable to hypertension on noise exposure. No association between hypertension and hearing impairment or noise-induced hearing loss (NIHL) was found.

Conclusion:

Our results support the association between ACE gene polymorphisms and occurrence of hypertension in noise-exposed workers.     

Minimal invasive para-rectus approach for limited open reduction and percutaneous fixation of displaced acetabular fractures

Introduction

Minimal invasive fixation has been reported as an alternative option for treatment of acetabular fractures to avoid blood loss and complications of extensive approaches. Closed reduction and percutaneous lag screw fixation can be done in minimally displaced acetabular fractures. Open reduction is indicated, if there is wide displacement. In this study, we report the use of a mini-open anterior approach to manipulate and reduce anteriorly displaced transverse acetabular fractures combined with percutaneous lag screw fixation.

Methods

This report included eight patients. All had anterior displaced simple transverse acetabular fractures. An oblique mini-incision was made above and medial to the mid-inguinal point, and lateral to the lateral border of rectus abdominis muscle. The external abdominal oblique aponeurosis was incised along its fibres. The arched fibres of internal abdominal oblique were displaced medially above the inguinal ligament to expose and incise the fascia transversalis. Care was taken to avoid injury of ilioinguinal nerve, inferior epigastric vessels, and spermatic cord. The external iliac vessels were palpated and protected laterally. A blunt long bone impactor was introduced through this small incision to manipulate and reduce the fracture under fluoroscopic control. Fluoroscopic guided percutaneous lag screw fixation was done in all patients.

Results

The average time to operation was 4 days. Average blood loss was 110 mL. Operative time averaged 95 min. Maximum fracture displacement averaged 10 mm preoperatively and 1.3 mm postoperatively. According to Matta score, anatomical reduction of the fracture was achieved in five patients and imperfect in three. Follow up averaged 27 months. Wound healing occurred without complications and fracture union was achieved without secondary displacement in all patients. Average time to fracture healing was 14 weeks. According to the modified Merle d’Aubigné score, functional outcome was good to excellent in all patients.

Discussion and conclusion

Limited open reduction can solve the problem of fracture reduction, which is the main concern in minimal invasive fixation of acetabular fractures. It may help the inclusion of displaced acetabular fractures for percutaneous lag screw fixation. This mini-para-rectus approach has the advantages of minimal soft tissue dissection with the possible anatomical reduction of simple transverse displaced acetabular fractures.     

Utilizing mixer torque rheometer in the prediction of optimal wet massing parameters for pellet formulation by extrusion/spheronization

In this study, we aimed to optimize theophylline pellet formulations using a two-factor three-level full-factorial design (3²) by monitoring the concentration of two pellet excipients, polyvinyl pyrrolidone K30 (PVP) binder solution (X1) and the hydrophilic excipient mannitol (X2). Their impact on pellet characteristics (responses) were evaluated. Increasing PVP concentration in the binder solution resulted in an increase in the wet mass torque value. The effect of mannitol, however, was antagonistic. Moreover, the pellet particle size was significantly influenced by the level of mannitol, PVP solution, and quadratic effect of mannitol. Mannitol significantly antagonized the pellet particle size. Furthermore, increased mannitol concentrations significantly enhanced drug dissolution rate from the pellets, whereas PVP concentration in the binder solution significantly reduced the drug dissolution rate. In conclusion, wet granulations can be controlled by monitoring the composition of the binder solution and pellet composition.     

Clinical outcome of HCV-positive patients with diffuse large B-cell lymphoma treated with rituximab-based chemotherapy

The influence of rituximab therapy on prognosis and hepatic toxicity (HT) in patients with hepatitis C virus (HCV)-positive diffuse large B-cell lymphoma (DLBCL) is unclear. Thus, we assessed HT and clinical outcome in patients with DLBCL and HCV infection who received rituximab-containing immunochemotherapy. We carried out a prospective analysis on a total of 280 HCV-positive patients with DLBCL, 200 of whom received chemotherapy plus rituximab (R-CHT), 80 received chemotherapy (CHT)-only. Survival outcomes and HT were compared according to rituximab administration. The median follow-up was 41 months. Addition of rituximab did not significantly affect prognosis (median progression-free survival, 40 vs 35 months, P?=?0.26; median overall survival, 51 vs 43 months P?=?0.09). Of 200 patients who received rituximab, 53 (26.5 %) had severe HT (grade 3–4), compared with 11 of 80 (13.75 %) patients who received rituximab-free regimens (P?=?0.033). Among patients treated with rituximab, 50 patients (25 %) did not complete planned course of therapy, 14 patients because of hepatic toxicity and 36 patients because of progressive disease. Pretreatment liver function impairment was predictive of severe HT. These results raise concerns regarding the routine use of rituximab with chemotherapy in individuals with HCV-positive DLBCL. However, more studies are warranted before a definitive conclusion can be made.     

Management of high-energy tibial plateau fractures by Ilizarov external fixator

Background

Despite the evolution of surgical techniques and implants, high energy tibial plateau fractures remain a challenging problem. The goals of treatment are to obtain a well-aligned stable joint with a painless functional range of motion and prevention of posttraumatic arthritis. Indirect reduction techniques and other soft tissue preservation methods safeguard the vascularity and emphasize restoring both joint congruity and the mechanical axis of the limb. The aim of this study was to evaluate the clinical outcome of using Ilizarov external fixator in the treatment of Schatzker type V–VI tibial plateau fracture.

Methods

This study was done during the period 2009–2011 for the treatment of 30 patients with high energy tibial plateau fractures (Schatzker type V in 17 and type VI in 13 patients) by Ilizarov external fixator. The mean age was 36 years .There were 23 males. The right limb was affected in 17 patients. There were 10 open fractures and other associated injuries in 9 patients.

Results

The mean of follow up period was 18 months. All the fractures were united in an average time of 15 weeks. There were pin track infection in 20 patients and other few complications in 8 patients. According to knee society score, there was an excellent result in 16.7 %, good in 60 %, fair in 20 %, and poor in 3.3 %.

Conclusion

Ilizarov external fixation is a safe and effective treatment option for high energy tibial plateau fractures with good functional results.     

When the brain expects pain: common neural responses to pain anticipation are related to clinical pain and distress in fibromyalgia and osteoarthritis

Supraspinal processes in humans can have a top‐down enhancing effect on nociceptive processing in the brain and spinal cord. Studies have begun to suggest that such influences occur in conditions such as fibromyalgia (FM), but it is not clear whether this is unique to FM pain or common to other forms of chronic pain, such as that associated with osteoarthritis (OA). We assessed top‐down processes by measuring anticipation‐evoked potentials and their estimated sources, just prior (< 500 ms) to laser heat pain stimulation, in 16 patients with FM, 16 patients with OA and 15 healthy participants, by using whole‐brain statistical parametric mapping. Clinical pain and psychological coping factors (pain catastrophizing, anxiety, and depression) were well matched between the patient groups, such that these did not confound our comparisons between FM and OA patients. For the same level of heat pain, insula activity was significantly higher in FM patients than in the other two groups during anticipation, and correlated with the intensity and extent of reported clinical pain. However, the same anticipatory insula activity also correlated with OA pain, and with the number of tender points across the two patient groups, suggesting common central mechanisms of tenderness. Activation in the dorsolateral prefrontal cortex was reduced during anticipation in both patient groups, and was related to less effective psychological coping. Our findings suggest common neural correlates of pain and tenderness in FM and OA that are enhanced in FM but not unique to this condition.     

Preoperative Prediction of Failure Following Two-Stage Revision for Knee Prosthetic Joint Infections

While two-stage revision is the gold standard for treatment of knee prosthetic joint infection (PJI), it is not without risk. The purpose of this study was to develop a tool to preoperatively predict the probability that a two-stage revision would fail to eradicate knee PJI. 3,809 surgical cases were retrospectively reviewed and data were collected from 314 charts. Overall, 105 (33.4%) cases failed to eradicate PJI using this procedure. Univariate analysis identified multiple variables independently associated with reinfection. Logistic regression was used to generate a model (bootstrap-corrected concordance index of 0.773) predicting failure of infection eradication. Preoperative knowledge of a high probability of failure may improve risk assessment, lead to more aggressive management, and allow for time to consider alternative therapies.     

The influence of physiological matrix conditions on permanent culture of induced pluripotent stem cell-derived cardiomyocytes

Cardiomyocytes (CMs) from induced pluripotent stem (iPS) cells mark an important achievement in the development of in vitro pharmacological, toxicological and developmental assays and in the establishment of protocols for cardiac cell replacement therapy. Using CMs generated from murine embryonic stem cells and iPS cells we found increased cell–matrix interaction and more matured embryoid body (EB) structures in iPS cell-derived EBs. However, neither suspension-culture in form of purified cardiac clusters nor adherence-culture on traditional cell culture plastic allowed for extended culture of CMs. CMs grown for five weeks on polystyrene exhibit signs of massive mechanical stress as indicated by α-smooth muscle actin expression and loss of sarcomere integrity. Hydrogels from polyacrylamide allow adapting of the matrix stiffness to that of cardiac tissue. We were able to eliminate the bottleneck of low cell adhesion using 2,5-Dioxopyrrolidin-1-yl-6-acrylamidohexanoate as a crosslinker to immobilize matrix proteins on the gels surface. Finally we present an easy method to generate polyacrylamide gels with a physiological Young's modulus of 55 kPa and defined surface ligand, facilitating the culture of murine and human iPS-CMs, removing excess mechanical stresses and reducing the risk of tissue culture artifacts exerted by stiff substrates.