Calmodulin antagonists inhibit and phorbol esters enhance transferrin endocytosis and iron uptake by immature erythroid cells

Seven antagonists of the calcium-binding protein calmodulin were found to inhibit iron and transferrin uptake by reticulocytes. This inhibition could be completely accounted for by inhibition of the endocytosis and exocytosis of transferrin. When four of the antagonists were tested with the nucleated erythroid cells from the liver of the fetal rat, inhibition of iron uptake was also observed but at higher concentrations than required for the same degree of inhibition with reticulocytes. The tumor promoters phorbol 12-myristate 13-acetate (PMA) and phorbol 12,13-dibutyrate (PDB) were shown to increase the rates of iron and transferrin uptake by reticulocytes and fetal liver erythroid cells by accelerating the rates of transferrin endocytosis and exocytosis. Since these substances are known to stimulate the calcium-activated enzyme protein kinase C while calmodulin antagonists are inhibitory, it is concluded that this enzyme plays an important role in the endocytosis and intracellular cycling of transferrin, and iron uptake by immature erythroid cells. However, the possibilities that calmodulin is also involved or that the inhibitory effects of the calmodulin antagonists are due to nonspecific actions on the cell membrane cannot be excluded.     

Neuronavigation by intraoperative three-dimensional ultrasound: initial experience during brain tumor resection

OBJECTIVE: Three-dimensional (3-D) ultrasound is an intraoperative imaging modality used in neuronavigation as an alternative to magnetic resonance imaging (MRI). This article summarizes 4 years of clinical experience in the use of intraoperative 3-D ultrasound integrated into neuronavigation for guidance in brain tumor resection. METHODS: Patients were selected for inclusion in the study on the basis of the size and location of their lesion. Preoperative 3-D MRI data were registered and used for planning as in other conventional neuronavigation systems. Intraoperative 3-D ultrasound images were acquired three to six times, and tumor resection was guided on the basis of these updated 3-D images. RESULTS: Intraoperative 3-D ultrasound represents a good solution to the problem of brain shift in neuronavigation because it easily provides an updated, and hence more accurate, map of the patient's true anatomy in all phases of the operation. Ultrasound makes it possible to follow the progression of the operation, and it improves the radicality of tumor resection by detecting tumor tissue that would remain if the imaging technology had not been used (in 53% of the cases). Integration of 3-D ultrasound with navigation technology solves the orientation problem experienced previously with two-dimensional ultrasound in neurosurgery. The technology makes it possible to directly compare intraoperative ultrasound and MRI data regarding visualization of the lesion. Ultrasound image quality is useful for guiding surgical procedures. CONCLUSION: Intraoperative 3-D ultrasound seems to provide a time- and cost-effective way to update high-quality 3-D maps used in neuronavigation.     

Systematic review of enhanced recovery after gastro-oesophageal cancer surgery

Introduction

Fast track methodology or enhanced recovery schemes have gained increasing popularity in perioperative care. While evidence is strong for colorectal surgery, its importance in gastric and oesophageal surgery has yet to be established. This article reviews the evidence of enhanced recovery schemes on outcome for this type of surgery.

Methods

A systematic literature search was conducted up to March 2014. Studies were retrieved and analysed using predetermined criteria.

Results

From 34 articles reviewed, 18 eligible studies were identified: 7 on gastric and 11 on oesophageal resection. Three randomised controlled trials, five case-controlled studies and ten case series were identified. The reported protocols included changes to each stage of the patient journey from pre to postoperative care. The specific focus following oesophageal resections was on early mobilisation, a reduction in intensive care unit stay, early drain removal and early (or no) contrast swallow studies. Following gastric resections, the emphasis was on reducing epidural anaesthesia along with re-establishing oral intake in the first three postoperative days and early removal of nasogastric tubes.In the papers reviewed, mortality rates following fast track surgery were 0.8% (9/1,075) for oesophageal resection and 0% (0/329) for gastric resection. The reported morbidity rate was 16.5% (54/329) following gastric resection and 38.6% (396/1,075) following oesophageal resection. Length of stay was reduced in both groups compared with conventional recovery groups in comparative studies.

Conclusions

The evidence for enhanced recovery schemes following gastric and oesophageal resection is weak, with only three (low volume) published randomised controlled trials. However, the enhanced recovery approach appears safe and may be associated with a reduction in length of stay.     

Tissue Motion and Strain in the Human Brain Assessed by Intraoperative Ultrasound in Glioma Patients

The objective of the study was to investigate tissue motion and strain imposed by cardiovascular pulsation in pathologic and normal brain parenchyma, as quantified from in vivo ultrasound data. Ultrasound acquired during surgery of 16 patients with glial tumors was retrospectively processed and analyzed. The tissue velocity was quantified at depths of 1 cm, 2 cm and 3 cm from brain cortex to investigate spatial dependency with depth. Comparison of strain and velocity in tumor and adjacent normal parenchyma was performed by selecting two regions-of-interest in the hyperechoic tumor and two regions in the low-echogenic areas interpreted as mainly normal tissue with some degree of tumor cell infiltration. The absolute maximum tissue velocity is seen to increase with increasing depths in 14 of 16 cases (87.5%). The maximum tissue velocities in the four regions close to the ultrasound visible tumor border are not statistically different (p = 0.163 to p = 0.975). The strain magnitudes are significantly higher in the regions with expected normal brain parenchyma than in regions with expected glial tumor tissue, both for the two regions being closest to the tumor border (p = 0.0004) and for the two regions further away from the tumor border (p = 0.0009). We conclude that the velocity of the brain parenchyma imposed by arterial pulsation during a cardiac cycle is generally increasing with increasing depth from cortex. The maximum velocity appears to be similar in regions with expected normal brain and tumor tissue, thus, does not seem to be affected by pathology. Strain magnitude is, however, a suitable parameter for discrimination of glial tumor and normal brain parenchyma. (E-mail: Tormod.Selbekk@sintef.no)     

No impact of early real-time PCR screening for respiratory viruses on length of stay and use of antibiotics in elderly patients hospitalized with symptoms of a respiratory tract infection in a single center in Norway

We tested the hypothesis that the results of real-time polymerase chain reaction (PCR) analyses for respiratory viruses would reduce antibiotic treatment and length of stay in elderly patients hospitalized with respiratory infections. Within 24 h of hospital admission, a total of 922 patients aged ≥60 years were interviewed for symptoms of ongoing respiratory tract infection. Symptomatic patients were swabbed for oropharyngeal/nasopharyngeal presence of viral pathogens immediately by members of the study group. During a 2-month period, non-symptomatic volunteers among interviewed patients were swabbed as well (controls). Oropharyngeal/nasopharyngeal swabs were analyzed with real-time PCR for nine common respiratory viruses. A total of 147 out of 173 symptomatic patients and 56 non-symptomatic patients (controls) agreed to participate in the study. The patients were allocated to three cohorts: (1) symptomatic and PCR-positive (S/PCR+), (2) symptomatic and PCR-negative (S/PCR?), or (3) non-symptomatic and PCR-negative (control). There were no non-symptomatic patients with a positive PCR result. A non-significant difference in the frequency of empiric antibiotic administration was found when comparing the S/PCR+ to the S/PCR? cohort; 16/19 (84 %) vs. 99/128 (77 %) (χ²?=?0.49). Antibiotic treatment was withdrawn in only two patients in the S/PCR+ cohort after receiving a positive viral diagnosis. The length of stay did not significantly differ between the S/PCR+ and the S/PCR? groups. We conclude that, at least in our general hospital setting, access to early viral diagnosis by real-time PCR had little impact on the antimicrobial treatment or length of hospitalization of elderly patients.