Aberrant expression of collapsin response mediator proteins-1, -2 and -5 in the brain of intrauterine growth restricted rats

Intrauterine growth restriction (IUGR) has been associated with increased perinatal morbidity, higher incidence of neurodevelopmental defects and increased risk for adult metabolic syndrome manifestations. Altered protein expression profiles associated with IUGR may be informative on the pathological mechanisms of this condition and might reveal potential markers for postnatal complications. We hypothesized that nutrient manipulation of the pregnant rat might influence the expression of important neurodevelopmental proteins in the resultant IUGR offspring. Therefore, we aimed to determine in newborn rat brain tissue the expression of collapsin response mediator proteins (CRMPs)-1, -2 and -5, commonly referred to as dihydropyrimidinase-related proteins (DPYLs) – playing a role in axon guidance, invasive growth and cell migration – and compare it to the corresponding expression in control rats. Two-dimensional electrophoresis and mass spectrometry, as well as Western blot analysis were employed in brain tissue from 24 IUGR newborn rats and 24 controls. With both methods, CRMP-1, CRMP-2 and CRMP-5 were decreased in the brains of the IUGR group as compared to the control group at the time of delivery. In conclusion, IUGR rat offspring are born with a decreased expression of CRMPs, suggesting that these proteins may be implicated in fetal stress-induced programming.     

Imaging Modalities for Renal Artery Stenosis in Suspected Renovascular Hypertension: Prospective Intraindividual Comparison of Color Doppler US,CT Angiography,GD-Enhanced MR Angiography,and Digital Substraction Angiography

The aim of the study was to evaluate the diagnostic accuracy of Color Doppler US, CT Angiography (CTA), and GD-enhanced MR Angiography (MRA) compared with digital subtraction angiography (DSA) for the detection of renal artery stenosis in patients with clinically suspected renovascular hypertension. Fifty-eight patients with suspected renovascular hypertension were enrolled in the study. All patients underwent Color Doppler US, CTA and GD-enhanced MRA. DSA was the gold standard method for the number of renal arteries, existence and degree of stenosis, or evidence of fibromuscular dysplasia. DSA depicted 132 renal arteries, 16 stenoses, and 4 arteries with fibromuscular dysplasia. Color Doppler US failed to detect 1 main and 14 polar arteries. CTA depicted all main renal arteries and 7/16 polar arteries, but failed to detect stenosis in two accessory vessels. Likewise, MRA did not detect stenotic accessory renal arteries, depicted 9/16 polar renal arteries, but missed two main renal arteries. All methods depicted the four main renal arteries with fibromuscular dysplasia. The overall sensitivity, specificity, and positive and negative predictive accuracy were 75%, 89.6%, 60% and 94.6%, respectively, for color Doppler US; 94%, 93%, 71%, and 99%, respectively, for CTA; and 90%, 94.1%, 75%, and 98%, respectively, for GD-enhanced MRA. CTA and GD-enhanced MRA have comparable and satisfactory results with respect to the negative predictive accuracy of the suspected renal artery stenosis. The concept of an imaging algorithm including US as screening test when appropriate and CTA or MRA as the second step-procedure is suggested. Therefore, DSA may be reserved for cases with major discrepancies or therapeutic interventions.     

The role of intraoperative micro-Doppler ultrasound in verifying proper clip placement in intracranial aneurysm surgery

Introduction

Aneurysmal subarachnoid hemorrhage constitutes a clinical entity associated with high mortality and morbidity. It is widely accepted that improper clip placement may have as a result of incomplete aneurysm occlusion and/or partial or complete obstruction of an adjacent vessel. Various modalities, including intraoperative or postoperative digital subtracting angiography, near-infrared indocyanine green angiography, micro-Doppler ultrasonography (MDU), and neurophysiological studies, have been utilized for verifying proper clip placement. The aim of our study was to review the role of MDU during aneurysmal surgery.

Methods

A literature search was performed using any possible combination of the following terms: “aneurysm,” “brain,” “cerebral,” “clip,” “clipping,” “clip malpositioning,” “clip repositioning,” “clip suboptimal positioning,” “Doppler,” “intracranial,” “microsurgery,” “micro-Doppler,” “residual neck,” “ultrasonography,” “ultrasound,” and “vessel occlusion”. Additionally, reference lists from the retrieved articles were reviewed for identifying any additional articles. Case reports and miniseries were excluded.

Results

A total of 19 series employing intraoperative MDU during aneurysmal microsurgery were retrieved. All studies demonstrated that MDU accuracy is extremely high. The highest reported false-positive rate of MDU was 2?%, while the false-negative rate was reported as high as 1.6?%. It has been demonstrated that the presence of subarachnoid hemorrhage, specific anatomic locations, and large size may predispose to improper clip placement. Intraoperative MDU’s technical limitations and weaknesses are adequately identified, in order to minimize the possibility of any misinterpretations.

Conclusion

Intraoperative MDU constitutes a safe, accurate, and low cost imaging modality for evaluating blood flow and for verifying proper clip placement during microsurgical clipping.     

Comparative study of quality of life and psychosocial characteristics in patients with psoriasis and leg ulcers

Psoriasis and leg ulcers have a marked impact on the patient's quality of life and represent a life‐long burden for affected patients. The aim of this study is to compare the quality of life, anxiety and depression, self‐esteem, and loneliness in patients with psoriasis and leg‐ulcer patients. Eighty patients with leg ulcers, eighty patients with psoriasis, and eighty healthy controls were included in this study. The quality of life, depression and anxiety, loneliness of the patient, and self‐esteem were assessed using the Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS), the UCLA loneliness Scale (UCLA‐Version 3), and the Rosenberg's Self‐esteem Scale (RSES), respectively. The DLQI score among patients with psoriasis was 12.74 ± 4.89 and leg ulcer patients was 13.28 ± 2.57. The patients with psoriasis presented statistically significant higher anxiety (9.87 ± 4.56) than both leg ulcer patients (8.26 ± 2.82) and controls (6.45 ± 1.89), while leg ulcer patients also presented higher anxiety than controls. Regarding self‐esteem, although there were no significant differences between the patients with psoriasis (15.25 ± 3.20) and the ones with leg ulcers (15.89 ± 2.93), they both presented statistically significant lower self‐esteem scores than control group (18.53 ± 3.04). The patients with psoriasis presented statistically significant higher levels of loneliness and social isolation (46.18 ± 6.63) compared to leg ulcer patients (43.73 ± 5.68) than controls (42.49 ± 3.41). Psoriasis and leg ulcers are long‐term skin diseases associated with significant impairment of the patient's quality of life, anxiety, and self‐esteem, which are frequently under‐recognized.     

Lung and 'end organ' injury due to mechanical ventilation in animals: comparison between the prone and supine positions

Introduction

Use of the prone position in patients with acute lung injury improves their oxygenation. Most of these patients die from multisystem organ failure and not from hypoxia, however. Moreover, there is some evidence that the organ failure is caused by increased cell apoptosis. In the present study we therefore examined whether the position of the patients affects histological changes and apoptosis in the lung and 'end organs', including the brain, heart, diaphragm, liver, kidneys and small intestine.

Methods

Ten mechanically ventilated sheep with a tidal volume of 15 ml/kg body weight were studied for 90 minutes. Five sheep were placed in the supine position and five sheep were placed in the prone position during the experiment. Lung changes were analyzed histologically using a semiquantitative scoring system and the extent of apoptosis was investigated with the TUNEL method.

Results

In the supine position intra-alaveolar hemorrhage appeared predominantly in the dorsal areas, while the other histopathologic lesions were homogeneously distributed throughout the lungs. In the prone position, all histological changes were homogeneously distributed. A significantly higher score of lung injury was found in the supine position than in the prone position (4.63 ± 0.58 and 2.17 ± 0.19, respectively) (P < 0.0001). The histopathologic changes were accompanied by increased apoptosis (TUNEL method). In the supine position, the apoptotic index in the lung and in most of the 'end organs' was significantly higher compared with the prone position (all P < 0.005). Interestingly, the apoptotic index was higher in dorsal areas compared with ventral areas in both the prone and supine positions (P < 0.003 and P < 0.02, respectively).

Conclusion

Our results suggest that the prone position appears to reduce the severity and the extent of lung injury, and is associated with decreased apoptosis in the lung and 'end organs'.     

Diffusion tensor imaging (DTI) in the detection of white matter lesions in patients with mild cognitive impairment (MCI)

Mild cognitive impairment (MCI) is recognized as a precursor to dementia. The amnestic MCI progresses usually to Alzheimer disease. Amnestic MCI multiple domain (md-MCI) seems to progress more rapidly than amnestic MCI single domain (a-MCI). In an attempt to identify patients at risk, we examined white matter changes in MCI subtypes using diffusion tensor imaging (DTI). We also tried to correlate DTI findings to neuropsychological tests. Forty-four amnestic single domain (a-MCI) patients, 19 amnestic multi domain (md-MCI), and 25 cognitively normal (NC) controls were included in the present study. All participants were assessed clinically using a battery of cognitive tests. DTI was performed to measure fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Areas studied were corpus callosum, posterior cingulum (PC), anterior cingulum (AC), and superior longitudinal fasciculus (SLF). ADC and FA of the above areas were related to the scores of certain neuropsychological tests that evaluate visual and verbal memory. No difference in DTI measurements was found between the two MCI subtypes. ADC in MCI cases was increased in comparison with NC in the genu, PC, right SLF, and left AC. FA was spared. Verbal memory was related to ADC of the genu, PC, right AC and right SLF, and to FA of the left SLF. Visual memory was related to ADC of the genu, PC, right AC, and SLF. The strongest correlation found was between the visual memory and the ADC of the right PC (Spearman ρ = 0.45, p < 0.001). DTI revealed that ADC was increased in certain brain areas in MCI patients. No difference in DTI measurements was found between the two MCI subtypes. DTI indices correlate with cognitive performance.     

Adjuvant chemotherapy and acute toxicity in hypofractionated radiotherapy for early breast cancer

AIM: To evaluate the effect of chemotherapy to the acute toxicity of a hypofractionated radiotherapy(HFRT) schedule for breast cancer. METHODS: We retrospectively analyzed 116 breast cancer patients with T1, 2N0 Mx. The patients received3-D conformal radiotherapy with a total physical dose of 50.54 Gy or 53.2 Gy in 19 or 20 fractions according to stage, over 23-24 d. The last three to four fractions were delivered as a sequential tumor boost. All patients were monitored for acute skin toxicity according to the European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group criteria. The maximum monitored value was taken as the final grading score. Multivariate analysis was performed for the contribution of age, chemotherapy and 19 vs 20 fractions to the radiation acute skin toxicity.RESULTS: The acute radiation induced skin toxicity was as following: grade Ⅰ 27.6%, grade Ⅱ 7.8% and grade Ⅲ 2.6%. No significant correlation was noted between toxicity grading and chemotherapy(P = 0.154, χ2 test). The mean values of acute toxicity score in terms of chemotherapy or not, were 0.64 and 0.46 respectively(P = 0.109, Mann Whitney test). No significant correlation was also noted between acute skin toxicity and radiotherapy fractions(P = 0.47, χ2test). According to univariate analysis, only chemotherapy contributed significantly to the development of acute skin toxicity but with a critical value of P = 0.05. However, in multivariate analysis, chemotherapy lost its statistical significance. None of the patients during the 2-years of follow-up presented any locoregional relapse.CONCLUSION: There is no clear evidence that chemotherapy has an impact to acute skin toxicity after an HFRT schedule. A randomized trial is needed for definite conclusions.