Detection of first- and second-order coherent motion in blindsight

Blindsight patients can detect fast moving stimuli presented within their blind field even when they deny any phenomenal visual experience. Although mounting evidence suggests the presence of different mechanisms and separate neural substrates underlying the processing of first-order (luminance-defined) and second-order (contrast-defined) motion, the perception of second-order motion in blindsight has scarcely been explored. In the present study, we investigated whether two blindsighted patients (GY and MS) can detect a variety of first- and second-order moving stimuli, and by using repetitive transcranial magnetic stimulation (rTMS), we assessed the role of V5/MT⁺ and V3⁺ in coherent motion processing. The hemianopes and four control subjects performed a two-interval forced-choice task in which they judged whether a pattern of coherently moving first-order or second-order textured squares moved in the first or second interval. They were not asked to report the direction of motion because neither of them could do so better than expected by chance. The results showed that MS, who has extensive destruction of the ventral cortical visual pathway as well as his V1 lesion, could not process second-order motion at all, whereas GY could perform second-order tasks but only at high-contrast modulation. This may have introduced first-order components in second-order moving stimuli and provided artifactual cues to motion. Moreover, rTMS delivered over area V5/MT⁺ impaired detection of both first- and second-order motion in undamaged control subjects, whereas rTMS over V3⁺ did not impair their performance in any of the stimuli employed. On the other hand, rTMS over V3⁺ did impair GY’s detection of first-order motion and high-contrast second-order moving textured squares that are likely to contain artifactual luminance cues. rTMS over V5/MT⁺ impaired first-order motion detection in MS. Overall, the results suggest that neither of the blindsight patients can detect artifact-free second-order motion.     

Spinal p38 mitogen-activated protein kinase mediates allodynia induced by first-degree burn in the rat

Activation of p38 mitogen-activated protein kinase (MAPK) in the spinal cord has been implicated in the development and maintenance of pain states. In this study, we tested whether p38 MAPK is involved in the response to first-degree burn of the hind paw. This injury induces central sensitization leading to tactile allodynia and is mediated by activation of Ca(2+) permeable AMPA/kainate receptors through PKC and PKA. We demonstrate that p38 MAPK is rapidly and robustly activated in the superficial spinal dorsal horn after mild thermal injury to the hind paw. Activated p38 MAPK was localized primarily to microglia and to a lesser extent in oligodendrocytes and lamina II neurons. Astrocytes were not involved in the p38 MAPK response. Intrathecal pretreatment of pharmacological inhibitors of p38 MAPK (SB203580, SD-282) dose-dependently blocked development of tactile allodynia, a characteristic of the first-degree burn model. The effects of the inhibitors on tactile allodynia were lost when they were administered after injury. These studies identify p38 MAPK as a major mediator of tactile allodynia, most likely activated downstream of AMPA/kainate receptors.     

Presynaptic M1, M2, and A1 receptors play roles in tetanic fade induced by pancuronium or cisatracurium

Purpose

We investigated whether presynaptic facilitatory M1 and/or inhibitory M2 muscarinic receptors contributed to pancuronium- and cisatracurium-induced tetanic fade.

Methods

Phrenic nerve-diaphragm muscle preparations of rats were indirectly stimulated with tetanic frequency (75 ± 3.3 Hz; mean ± SD). Doses of pancuronium, cisatracurium, hexamethonium, and d-tubocurarine for producing approximately 25% fade were determined. The effects of pirenzepine and methoctramine, blockers of presynaptic M1 and M2 receptors, respectively, on the tetanic fade were investigated.

Results

The concentrations required for approximately 25% fade were 413 µM for hexamethonium (26.8 ± 2.4% 4% fade), 55 nM for d-tubocurarine (28.7 ± 2.55% fade), 0.32 µM for pancuronium (25.4 ± 2.2% fade), and 0.32 µM for cisatracurium (24.7 ± 0.8% fade). Pirenzepine or methoctramine alone did not produce the fade. Methoctramine, 1 µM, attenuated the fade induced by hexamethonium (to 16.0 ± 2.5% fade), d-tubocurarine (to 6.0 ± 1.6 fade), pancuronium (to 8.0 ± 4.0% fade), and cisatracurium (to 11.0 ± 3.3% fade). 10 nM pirenzepine attenuated only the fades produced by pancuronium (to 5.0 ± 0.11% fade) and cisatracurium (to 13.3 ± 5.3% fade). Cisatracurium (0.32 µM) showed antiacetylcholinesterase activity (in plasma, 14.2 ± 1.6%; 6%; in erythrocyt 17.2 ± 2.66%) similar to that of pancuronium (0.32 µM). The selective A1 receptor blocker, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 2.5 nM), also attenuated the fades induced by pancuronium and cisatracurium.

Conclusion

The tetanic fades produced by pancuronium and cisatracurium depend on the activation of presynaptic inhibitory M2 receptors; these agents also have anticholinesterase activities. The fades induced by these agents also depend on the activation of presynaptic inhibitory A1 receptors through the activation of stimulatory M1 receptors by acetylcholine.     

Plasma acylated ghrelin levels are higher in patients with chronic atrophic gastritis

OBJECTIVES: Ghrelin is mainly produced by the endocrine cells of the gastric oxyntic mucosa. For this reason we decided to investigate the modification of the circulating levels not only of total but also of acylated ghrelin in a series of patients with chronic atrophic gastritis. DESIGN: Twenty-five patients with chronic atrophic gastritis and 25 healthy subjects were studied. In all 50 subjects gastrin and total and acylated ghrelin levels were evaluated. All patients underwent endoscopy with multiple biopsies, and the possibility of Helicobacter pylori infection was investigated. RESULTS: Significantly higher acylated ghrelin levels (82.8 +/- 61.3 vs. 35.1 +/- 17.1 pmol/l), acylated/total ghrelin ratio (0.422 +/- 0.202 vs. 0.152 +/- 0.085) and gastrin levels (1071 +/- 816 vs. 66 +/- 22 ng/l) were observed in the 25 patients with chronic atrophy than in the healthy subjects. Otherwise, no significant relationships were found when total ghrelin was correlated with the presence of atrophy, or with gastrin levels. In the healthy subjects, but not in the patients, acylated and total ghrelin levels were significantly higher in female than in male patients. CONCLUSIONS: The increase in acylated ghrelin levels and in the acylated/total ghrelin ratio in patients with atrophy of the body and fundus can be explained by hypothesizing an increase in the acylating process in the presence of gastric atrophy. It suggests that there may be a compensatory increase in plasma active ghrelin concentration in response to gastric atrophy, a condition which causes a loss of ghrelin-producing cells and an increase in gastric pH.     

Patient risk of contact with respiratory pathogens from inanimate surfaces in a cystic fibrosis outpatient clinic. A prospective study over a four-year period

Acquisition of respiratory pathogens such as Pseudomonas aeruginosa (PA) is associated with increased morbidity and mortality in cystic fibrosis (CF). Research on the prevalence of these pathogens on environmental surfaces of a CF Center is scanty, and so far no study has determined what risk CF patients have of coming in contact with them during their visits to the CF Center. This study is aimed at assessing the prevalence of some respiratory pathogens in samples taken systematically during a 4-year period from inanimate surfaces and sinks in a CF Outpatient Clinic, and to estimate the risk that a non-PA colonized CF patient has of contact with PA when visiting the CF Center. Microbiological samples were taken and cultured from the inanimate surfaces and sinks of the Outpatient clinic of a CF Center once a month from 2001 to 2005. Four hundred and sixty environmental specimens were collected: 36.3% were positive for respiratory pathogens (23% of rooms' inert surfaces, 49.5% of sinks). Achromobacter xylosoxidans was found in 0.8% of surface samples. PA was isolated in 22.8% samples. The estimated risk for each non-colonized patient of coming in contact with PA on the surfaces in the Clinic at each visit was 5.4 per thousand (CI95% 0.9-30.1). Genotyping of a sample of environmental PA strains revealed a genetic relation between environmental and clinical isolates in most cases. Micro-organisms relevant for CF patients can be found on inanimate surfaces of a CF Center, although the risk for patients of coming in contact with PA during their visits to the CF center seems low.     

Cigarette smoke facilitates allergen penetration across respiratory epithelium

Background:  The association between cigarette smoke exposure and allergic airway disease is a matter for debate. We sought to investigate in an in vitro system whether active smoking reduces the integrity and barrier function of the respiratory epithelium and thus facilitates allergen penetration.
Methods:  We cultured the human bronchial epithelial cell line 16HBE14o− in a transwell culture system as a surrogate for the intact respiratory epithelium. The cell monolayer was exposed to standardized cigarette smoke extract (CSE). The extent and effects of trans-epithelial allergen penetration were measured using ¹²⁵I-labelled purified major respiratory allergens (rBet v 1, rPhl p 5 and rDer p 2) and histamine release experiments.
Results:  Exposure of cells to concentrations of CSE similar to those found in smokers induced the development of para-cellular gaps and a decrease in trans-epithelial resistance. CSE exposure induced a more than threefold increase in allergen penetration. Increased subepithelial allergen concentrations provoked a substantial augmentation of histamine release from sensitized basophils.
Conclusions:  Our results indicate that cigarette smoke is a potent factor capable of reducing the barrier function of the respiratory epithelium for allergens and may contribute to increased allergic inflammation, exacerbation of allergic disease and boosting of IgE memory.     

Severe road traffic injuries in Kenya, quality of care and access

Background

Road traffic injuries (RTI) are on increase in developing countries. Health care facilities are poorly equipped to provide the needed services.

Objective

Determine access and quality of care for RTI casualties in Kenya.

Design

Cross-sectional survey

Setting

53 large and medium size private, faith-based and public hospitals.

Participants

In-patient road traffic crash casualties and health personnel in the selected hospitals were interviewed on availability of emergency care and resources. Onsite verification of status was undertaken.

Results

Out of 310 RTI casualties interviewed, 72.3%, 15.6% and 12.2% were in public, faith-based and private hospitals, respectively. Peak age of the injured was 15–49 years. First aid was availed to 16.0% of casualties. Unknown persons transported 76.5% of the injured. Police and ambulance vehicles transported 6.1% and 1.4%, respectively. 51.9% reached health facilities within 30 minutes of crash and medical care provided to 66.2% within one hour. 40.8% of recipient facilities were adequately prepared for RTI emergencies.

Conclusions

Most RTI casualties were young and from poor backgrounds. Training of motorists and general public in first aid should be considered in RTI control initiatives. Availability of basic trauma care medical supplies in public health facilities was highly deficient.     

The acute skin and heart toxicity of a concurrent association of trastuzumab and locoregional breast radiotherapy including internal mammary chain: A single-institution study

Background

To evaluate the skin and heart toxicity of a concurrent adjuvant trastuzumab-radiotherapy for breast cancer (BC), especially in the case of internal mammary chain (IMC) irradiation.

Material and methods

Prospective study of 106 patients treated between 06/2003 and 03/2007 by concurrent trastuzumab-radiotherapy for non-metastatic BC. Left ventricular ejection fractions (LVEF) was assessed at baseline, before and after radiotherapy and then every 4-6 months. All toxicities were evaluated using CTCAEV3.

Results

Median age was 52 years (25-76). Chemotherapy with anthracycline was administered in 92% of patients. All patients received trastuzumab every three weeks (8 mg/kg followed by 6 mg/kg) for a median duration of 12 months (3-40). The IMC was irradiated in 83% of patients. There were: 87 grade 1, 14 grade 2 and 2 grade 3 skin reactions. There were 13 oesophagitis: 9 grade 1; 3 grade 2, and 1 grade 3. Out of 101 patients with assessments after 6 months, late telangiectasia grade 1 occurred in 5 patients, local pain grade 1 in 19 patients and grade 2 in 3 patients, fibrosis grade 1 in 16 patients. A reversible grade ?2 left ventricular systolic dysfunction occurred in 6 patients.

Conclusion

In this prospective study of breast cancer patients treated with trastuzumab-radiotherapy with, in most cases, anthracycline-based chemotherapy and IMC irradiation, both the rate of abnormal LVEF after concurrent trastuzumab-radiotherapy and the skin toxicity were deemed acceptable. Further follow-up is needed.     

203 Hypoxic Leukemic Microenvironment and its Targeting by the Hypoxia-Activated Prodrug PR-104

We investigated whether hypoxia was a contributing factor in the protective role of the BM microenvironment. We observed a marked expansion of hypoxic BM areas in several leukemia models. This observation was exploited via the use of the hypoxia activated drug PR-104.

Full Abstract

It has recently became clear that a physiological oxygen gradient exists within the bone marrow (BM) with hematopoietic stem cells (HSCs) residing in the more anoxic regions. Interactions between leukemia cells and bone marrow (BM) microenvironment are known to promote leukemia cell survival and confer resistance to drugs commonly used in the management of this disease. We investigated whether hypoxia was a contributing factor in the protective role of the BM microenvironment. We observed a