Quantitative evaluation of bronchoalveolar lavage for the treatment of severe Mycoplasma pneumoniae pneumonia in children-A new complementary index: Bronchial Insufflation Sign Score.

OBJECTIVE: The aim of this study was to investigate the value of Broncoplasma Insufflation Sign in lung ultrasound signs in assessing the efficacy of bronchoalveolar lavage in severe Mycoplasma pneumoniae pneumonia in children. METHODS: Forty-seven children with severe Mycoplasma pneumoniae pneumonia were treated with medication and bronchial lavage. Laboratory and imaging results were collected, and lung ultrasonography was performed before bronchoalveolar lavage and 1, 3, and 7 days after lavage to record changes in Bronchial Insufflation Sign and changes in the extent of solid lung lesions. Factors affecting the effectiveness of bronchoalveolar lavage were analyzed using logistic regression and other factors. RESULTS: Bronchial Insufflation Sign Score and the extent of lung solid lesions were the factors affecting the effectiveness of bronchoalveolar lavage treatment. The smaller the area of lung solid lesions and the higher the Bronchial Insufflation Sign Score, the more effective the results of bronchoalveolar lavage treatment were, and the difference was statistically significant, with a difference of p < 0.05. The Bronchial Insufflation Sign Score had the highest sensitivity and specificity for the prediction of the efficacy of bronchoalveolar lavage treatment in the first 7 days after the treatment. CONCLUSION: Bronchial Insufflation Sign Score combined with the extent of solid lung lesions can assess the efficacy of bronchoalveolar lavage in the treatment of severe Mycoplasma pneumoniae pneumonia in children; lung ultrasound is a timely and effective means of assessing the efficacy of bronchoalveolar lavage.

Association of the LRRK2 genetic polymorphisms with leprosy in Han Chinese from Southwest China.

Leprosy is a chronic infectious and neurological disease that is caused by infection of Mycobacterium leprae (M. leprae). A recent genome-wide association study indicated a suggestive association of LRRK2 genetic variant rs1873613 with leprosy in Chinese population. To validate this association and further identify potential causal variants of LRRK2 with leprosy, we genotyped 13 LRRK2 variants in 548 leprosy patients and 1078 healthy individuals from Yunnan Province and (re-)analyzed 3225 Han Chinese across China. Variants rs1427267, rs3761863, rs1873613, rs732374 and rs7298930 were significantly associated with leprosy per se and/or paucibacillary leprosy (PB). Haplotype A-G-A-C-A was significantly associated with leprosy per se (P=0.018) and PB (P=0.020). Overexpression of the protective allele (Thr2397) of rs3761863 in HEK293 cells led to a significantly increased nuclear factor of activated T-cells' activity compared with allele Met2397 after lipopolysaccharides stimulation. Allele Thr2397 could attenuate 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced autophagic activity in U251 cells. These data suggest that the protective effect of LRRK2 variant p.M2397T on leprosy might be mediated by increasing immune response and decreasing neurotoxicity after M. leprae loading. Our findings confirm that LRRK2 is a susceptible gene to leprosy in Han Chinese population.

Ultra-early electroacupuncture rehabilitation for intravenous thrombolysis-induced cerebral infarction.

OBJECTIVE: The purpose of this research was to investigate whether it is possible to perform ultra-early interventional electroacupuncture on individuals who had experienced intravenous thrombolysis prior to receiving therapy for acute cerebral infarction. PATIENTS AND METHODS: Patients who have undergone intravenous thrombolysis between July 2019 and March 2021 were eligible for participation in this study. The participants were divided into two groups; one group received electroacupuncture therapy 24 hours after their condition became stable, while the other group received treatment 48 hours after their condition became stable. Both groups received the same therapy for their respective forms of rehabilitation. The Fugl-Meyer Motion Assessment Scale (FMA) was used to assess the patients' motor function before and after therapy, as well as two weeks and one month after treatment. The scores of the FMA were recorded before and after treatment. RESULTS: After therapy, the FMI scores were higher in both groups (p<0.05), and the researchers found that the ultra-early electroacupuncture intervention was related to higher FMI ratings 2 weeks and 1 month after treatment (p<0.05). In neither of the two study groups was there any sign of a major adverse response or consequence (p>0.05). CONCLUSIONS: This research offers evidence that ultra-early interventional electroacupuncture rehabilitation therapy may be an effective and safe method of treatment for individuals who have had a cerebral infarction after receiving intravenous thrombolysis. The results lend credence to the notion that this kind of therapy should be taken into consideration as an adjunctive model for rehabilitation in patients of this type.

Correlation between miR-1207-5p expression with steroid-induced necrosis of femoral head and VEGF expression.

OBJECTIVE: The aim of this study was to investigate the expression level of micro-ribonucleic acid-1207-5p (miR-1207-5p) in steroid-induced necrosis of femoral head (SNFH) and its correlation with SNFH. Meanwhile, we also aimed to analyze the relationship between miR-1207-5p expression and vascular endothelial growth factor (VEGF) in the femoral head. PATIENTS AND METHODS: From May 2016 to December 2017, 60 patients aged (55.4±8.7) were selected in our hospital. All patients were diagnosed and confirmed as SNFH. Total RNA was extracted from the necrotic femoral head tissues and peripheral blood. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was used to detect the expression level of miR-1207-5p in tissues. At the same time, immunohistochemistry and Western blotting were adopted to detect VEGF expression in the bone tissue of patients with high or low expression of miR-1207-5p. 7 patients with femoral neck fracture aged (45.6±4.51) were enrolled in the control group. In the animal experiment, the rat SNFH model was established by intraperitoneal injection of lipopolysaccharide and methylprednisolone. Subsequently, the expression levels of miR-1207-5p and VEGF in necrotic femoral tissues were detected. Meanwhile, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was applied to detect cell apoptosis in bone lacunae of miR-1207-5p high expression group and miR-1207-5p low expression group, respectively. RESULTS: The expression level of miR-1207-5p in the necrotic bone tissue of the SNFH group was significantly higher than that of the control group. The expression level of miR-1207-5p was inversely proportional to Harris Hip score (p<0.05). A higher expression of miR-1207-5p indicated a lower expression level of VEGF (p<0.05). The animal experimental results revealed that miR-1207-5p expression in the necrotic femoral head tissue of SNFH group was significantly higher than that of the control group. Furthermore, the number of apoptotic cells in bone lacunae was remarkably higher in miR-1207-5p high expression group (p<0.05). CONCLUSIONS: MiR-1207-5p is significantly up-regulated in necrotic femoral head tissue and serum of SNFH patients. Meanwhile, its expression level is inversely proportional to Harris Hip score of patients. The possible underlying mechanism may be related to the inhibitory effect of miR-1207-5p on VEGF.

[To reconstruct facial defects after removing skin lesions by using local flap].

Objective:The aim of this study is to investigate the method and effect of reconstruction of facial skin defects after removing the lesions by applying local flap. Method:Fifty-three patients （30 males and 23 females） with facial skin lesions. Complete surgical resection of the lesion; malignant tumor resection should be strictly non-tumor principle; intraoperative frozen section pathological examination confirmed negative margin; benign lesions can be cut off the lesion. According to the defect site, the appropriate local flap was used to repair the defect: 13 cases of modified VY propulsion flap, 8 cases of nasolabial flap, 8 cases of A/O-T shaped flap, 6 cases of rotating flap, 5 cases of direct sliding flap, multi-type There were 6 cases with flap, 2 cases with double leaf, 2 cases with prismatic flap and 3 cases with free flap. Result:Patients with malignant tumor were followed for 12-36 months postoperatively while followed for 10-12 months in the benign. Two patients with malignant tumor developed local recurrence and removed again. At half a year after first resection. Distal partial necrosis occurred in 5 cases while the wound dehiscence in1case, others were well developed. No others major complications occurred. Conclusion:There are various types of local skin flap for repairing facial skin defects. It is very important to excise the primary lesion radically before reconstruction,the satisfactory curative effect can be obtained through reasonable design of the flap.

Serial T2-Weighted Magnetic Resonance Images Acquired on a 1.5 Tesla Magnetic Resonance Linear Accelerator Reveal Radiomic Feature Variation in Organs at Risk: An Exploratory Analysis of Novel Metrics of Tissue Response in Prostate Cancer.

"Delta-radiomics" investigates variations in quantitative image metrics over time and can yield important clinical information. We hypothesized that in patients undergoing active radiation therapy (RT) for prostate cancer (PCa), there would exist observable variation in the quantitative metrics that describe the T2-weighted (T2W) intensity histogram in the prostate and surrounding organs at risk (OAR) over time. We investigated the feasibility of acquisition and subsequent analysis of the delta-radiomic profiles of these regions of interest (ROI) in serial T2W magnetic resonance (MR) images obtained on a 1.5 Tesla (T) Magnetic Resonance Linear Accelerator (MRL). Principally, we sought to illustrate the significance of longitudinal radiomic data acquisition for tissue response monitoring and provide a framework for future hypothesis driven research. Patients with PCa undergoing treatment with RT were compiled from an ongoing prospective observational imaging trial using a 1.5 T MRL (NCT30500081). Contiguous axial slices of prostate parenchyma were contoured and temporally normalized to sections of Sartorius muscle which served as a control. Similarly, contiguous sections of rectal and bladder wall adjacent to the prostate were contoured and temporally normalized to regions of these organs further removed from the planning target volume (PTV). First order statistical descriptors of the T2W intensity histogram were extracted and evaluated for changes over time using linear mixed effects regression modeling and post-hoc contrasts. Benjamini-Hochberg corrections were employed to reduce the effects of multiple testing and control for the false discovery rate (FDR). Four patients with a median age of 69 comprised this exploratory cohort. One patient had low-risk disease, two had intermediate (one favorable, one unfavorable), and one had high risk disease. Three out of four patients underwent definitive radiation to 75.6 Gray (Gy) in 42 fractions and one received hypofractionated therapy to a total dose of 70 Gy over 28 fractions, and all received treatment on a conventional linear accelerator. The most significant acute toxicity event was grade 2 GU dysfunction observed in two patients. Follow up ranged from 1 month to 10 months post treatment, and no long-term complications were reported in patients who completed treatment at least one month prior. Bladder wall adjacent to the prostate demonstrated significant variation in the mean and median metric values after the first week of treatment. In addition, rectal wall adjacent to the prostate exhibited significant variation in the mean, median, and standard deviation metric values by the second week of treatment. No significant variation in any radiomic feature was observed in the Sartorius control. This exploratory study is one of the earliest examining the delta-radiomic characteristics of the T2W intensity histogram in OAR extracted from images acquired on a 1.5 T MRL in patients actively being treated with RT for PCa. We demonstrated a feasible approach to longitudinal radiomic data acquisition providing limitless opportunity for future research. Analysis of the delta-radiomic profiles in OAR revealed significant variation in metrics after only one week of RT in bladder and rectal wall adjacent to the prostate. These findings must be further investigated and validated with expanded data sets with long-term follow up and correlation to clinical outcomes including toxicity and tumor control.

Lyman-Kutcher-Burman NTCP model parameters for radiation pneumonitis and xerostomia based on combined analysis of published clinical data.

Knowledge of accurate parameter estimates is essential for incorporating normal tissue complication probability (NTCP) models into biologically based treatment planning. The purpose of this work is to derive parameter estimates for the Lyman-Kutcher-Burman (LKB) NTCP model using a combined analysis of multi-institutional toxicity data for the lung (radiation pneumonitis) and parotid gland (xerostomia). A series of published clinical datasets describing dose response for radiation pneumonitis (RP) and xerostomia were identified for this analysis. The data support the notion of large volume effect for the lung and parotid gland with the estimates of the n parameter being close to unity. Assuming that n = 1, the m and TD(50) parameters of the LKB model were estimated by the maximum likelihood method from plots of complication rate as a function of mean organ dose. Ninety five percent confidence intervals for parameter estimates were obtained by the profile likelihood method. If daily fractions other than 2 Gy had been used in a published report, mean organ doses were converted to 2 Gy/fraction-equivalent doses using the linear-quadratic (LQ) formula with alpha/beta = 3 Gy. The following parameter estimates were obtained for the endpoint of symptomatic RP when the lung is considered a paired organ: m = 0.41 (95% CI 0.38, 0.45) and TD(50) = 29.9 Gy (95% CI 28.2, 31.8). When RP incidence was evaluated as a function of dose to the ipsilateral lung rather than total lung, estimates were m = 0.35 (95% CI 0.29, 0.43) and TD(50) = 37.6 Gy (95% CI 34.6, 41.4). For xerostomia expressed as reduction in stimulated salivary flow below 25% within six months after radiotherapy, the following values were obtained: m = 0.53 (95% CI 0.45, 0.65) and TD(50) = 31.4 Gy (95% CI 29.1, 34.0). Although a large number of parameter estimates for different NTCP models and critical structures exist and continue to appear in the literature, it is hard to justify the use of any single parameter set obtained at a selected institution for the purposes of biologically based treatment planning. Our expectation is that the proposed model parameters based on cumulative experience at various institutions are more representative of the overall practice of radiation therapy than any single-institution data, and could be more readily incorporated into clinical use.

Competitive inhibition of a set of endoplasmic reticulum protein genes (GRP78, GRP94, and ERp72) retards cell growth and lowers viability after ionophore treatment.

GRP78, a 78-kDa protein localized in the endoplasmic reticulum (ER), has been implicated in protein processing and stress protection. Its promoter contains a 36-bp region which is conserved among GRP genes across species and has the ability to compete for trans-acting factors mediating GRP gene expression. Integration of about 800 tandem copies of this sequence into the genome of a Chinese hamster ovary cell line (DG44) results in transfectants with the following phenotypes: (i) the induction level of GRP78 by the calcium ionophore A23187 and tunicamycin is reduced 4- and 2-fold, respectively, (ii) the induction levels of two other ER luminal protein genes, GRP94 and ERp72, are simultaneously down-regulated, (iii) the growth rate of these cells is half that of transfectants without the amplified sequence, and (iv) cell viability is decreased by 25-fold after A23187 treatment. These results provide new evidence that ERp72 shares common trans-acting regulatory factors with the GRP genes and that a reduction of this set of ER proteins correlates with lower viability after ionophore treatment.

Recommendations for MRI-based contouring of gross tumor volume and organs at risk for radiation therapy of pancreatic cancer.

PURPOSE: Local recurrence is a common and morbid event in patients with unresectable pancreatic adenocarcinoma. A more conformal and targeted radiation dose to the macroscopic tumor in nonmetastatic pancreatic cancer is likely to reduce acute toxicity and improve local control. Optimal soft tissue contrast is required to facilitate delineation of a target and creation of a planning target volume with margin reduction and motion management. Magnetic resonance imaging (MRI) offers considerable advantages in optimizing soft tissue delineation and is an ideal modality for imaging and delineating a gross tumor volume (GTV) within the pancreas, particularly as it relates to conformal radiation planning. Currently, no guidelines have been defined for the delineation of pancreatic tumors for radiation therapy treatment planning. Moreover, abdominal MRI sequences are complex and the anatomy relevant to the radiation oncologist can be challenging. The purpose of this study is to provide recommendations for delineation of GTV and organs at risk (OARs) using MRI and incorporating multiple MRI sequences. METHODS AND MATERIALS: Five patients with pancreatic cancer and 1 healthy subject were imaged with MRI scans either on 1.5T or on 3T magnets in 2 separate institutes. The GTV and OARs were contoured for all patients in a consensus meeting. RESULTS: An overview of MRI-based anatomy of the GTV and OARs is provided. Practical contouring instructions for the GTV and the OARs with the aid of MRI were developed and included in these recommendations. In addition, practical suggestions for implementation of MRI in pancreatic radiation treatment planning are provided. CONCLUSIONS: With this report, we attempt to provide recommendations for MRI-based contouring of pancreatic tumors and OARs. This could lead to better uniformity in defining the GTV and OARs for clinical trials and in radiation therapy treatment planning, with the ultimate goal of improving local control while minimizing morbidity.

An online replanning method using warm start optimization and aperture morphing for flattening-filter-free beams.

PURPOSE: In a situation where a couch shift for patient positioning is not preferred or prohibited (e.g., MR-linac), segment aperture morphing (SAM) can address target dislocation and deformation. For IMRT/VMAT with flattening-filter-free (FFF) beams, however, SAM method would lead to an adverse translational dose effect due to the beam unflattening. Here the authors propose a new two-step process to address both the translational effect of FFF beams and the target deformation. METHODS: The replanning method consists of an offline and an online step. The offline step is to create a series of preshifted-plans (PSPs) obtained by a so-called "warm start" optimization (starting optimization from the original plan, rather than from scratch) at a series of isocenter shifts. The PSPs all have the same number of segments with very similar shapes, since the warm start optimization only adjusts the MLC positions instead of regenerating them. In the online step, a new plan is obtained by picking the closest PSP or linearly interpolating the MLC positions and the monitor units of the closest PSPs for the shift determined from the image of the day. This two-step process is completely automated and almost instantaneous (no optimization or dose calculation needed). The previously developed SAM algorithm is then applied for daily deformation. The authors tested the method on sample prostate and pancreas cases. RESULTS: The two-step interpolation method can account for the adverse dose effects from FFF beams, while SAM corrects for the target deformation. Plan interpolation method is effective in diminishing the unflat beam effect and may allow reducing the required number of PSPs. The whole process takes the same time as the previously reported SAM process (5-10 min). CONCLUSIONS: The new two-step method plus SAM can address both the translation effects of FFF beams and target deformation, and can be executed in full automation except the delineation of target contour required by the SAM process.

MRI-guided prostate adaptive radiotherapy - A systematic review.

Dose escalated radiotherapy improves outcomes for men with prostate cancer. A plateau for benefit from dose escalation using EBRT may not have been reached for some patients with higher risk disease. The use of increasingly conformal techniques, such as step and shoot IMRT or more recently VMAT, has allowed treatment intensification to be achieved whilst minimising associated increases in toxicity to surrounding normal structures. To support further safe dose escalation, the uncertainties in the treatment target position will need be minimised using optimal planning and image-guided radiotherapy (IGRT). In particular the increasing usage of profoundly hypo-fractionated stereotactic therapy is predicated on the ability to confidently direct treatment precisely to the intended target for the duration of each treatment. This article reviews published studies on the influences of varies types of motion on daily prostate position and how these may be mitigated to improve IGRT in future. In particular the role that MRI has played in the generation of data is discussed and the potential role of the MR-Linac in next-generation IGRT is discussed.

Binding of serum amyloid P component to heparin in human serum.

It has been proposed that the function of serum amyloid P component (SAP) may closely relate with its binding to polysaccharides, especially glycosaminoglycans. We employed a quantitative immunoelectrophoresis (QIE) method and a native polyacrylamide gel electrophoresis (PAGE) method to characterize the SAP-heparin binding in soluble state. The SAP-heparin binding showed positive cooperativity. The apparent numbers of heparin molecules bound to SAP varied with the calcium concentration with a ratio of 1:1 (SAP/heparin), a Kd of 2.06 x 10(-7) M at 0.1 mM CaCl2 and a ratio of 1:1.6 (SAP/heparin), a Kd of 3.91 x 10(-7) M at 2 mM CaCl2, when estimated by the QIE method. No binding between SAP and heparin was observed in the absence of calcium. Magnesium and barium failed to induce the formation of SAP-heparin complex. Furthermore, they showed inhibitory effects on the calcium-mediated complex formation. We propose that heparin might be a regulator to modulate the anticoagulant activity of SAP and a useful drug to prevent SAP deposition on amyloid deposits.

Cloning and characterization of a novel human gene encoding a zinc finger protein with 25 fingers.

This study reports cloning and characterization of a human cDNA encoding a novel human zinc finger protein, ZFD25. ZFD25 cDNA is 6118 bp long and has an open reading frame of 2352 bp that encodes a 783 amino acid protein with 25 C2H2-type zinc fingers. The ZFD25 cDNA also contains a region with high sequence similarity to the Krüppel-associated box A and B domain in the 5'-untranslated region, suggesting that ZFD25 belongs to the Krüppel-associated box zinc finger protein family. The ZFD25 gene was localized to chromosome 7q11.2. Northern blot analysis showed that ZFD25 was expressed in a wide range of human organs. In cultured endothelial cells, the mRNA level was decreased upon serum starvation.

The rat 78,000 dalton glucose-regulated protein (GRP78) as a precursor for the rat steroidogenesis-activator polypeptide (SAP): the SAP coding sequence is homologous with the terminal end of GRP78.

Based on the striking sequence identity between the amino acid sequence of rat steroidogenesis-activator polypeptide (SAP) and the carboxyl terminus of the 78,000 dalton glucose-regulated protein (GRP78), the precursor-product relationship between GRP78 and SAP was investigated in Leydig cells. Immunoblot analysis with peptide antibodies specific for GRP78 and SAP showed that the putative SAP precursor is also immunoreactive with the anti-GRP78 antibody. Genomic blot hybridizations further revealed that GRP78 is neither rearranged nor amplified in the H-540 Leydig cell tumor, the original source for SAP. Further, there appears to be a single copy of the SAP coding sequence within the rat genome. This sequence resides within the last exon of GRP78. Our observations support the hypothesis that, in steroidogenic cells, SAP is likely to be derived from posttranslational processing of a very minor fraction of GRP78.

Dose effects of guide wires for catheter-based intravascular brachytherapy.

PURPOSE: Guide wires with high torquability and steerability are commonly used to navigate through a tortuous and/or branching arterial tree in a catheter-based intravascular brachytherapy procedure. The dosimetric effects due to the presence of metallic guide wires have not been addressed. This work investigates these dose effects for the three most commonly used beta and gamma sources (90Sr, 32P, and 192Ir). METHODS AND MATERIALS: The EGS4 Monte Carlo codes were used to calculate the dose distributions for the 90Sr(NOVOSTE), 32P (Guidant), and 192Ir (BEST Ind.) with and without a guide wire in place. Energy spectra for particles exiting the sources were calculated from the full phase-space data obtained from the Monte Carlo simulations of the source constructions. Guide wires of various thicknesses and compositions were studied. RESULTS: The dose perturbations due to the presence of guide wires were found to be far more significant for the 90Sr/90Y and 32P beta sources than those for the 192Ir gamma source. Because of the attenuation by the guide wires, a dose reduction of up to 60% behind a guide wire was observed for the beta sources, whereas the dose perturbation was found to be negligible for the gamma source. For a beta source, the dose perturbations depend on the thickness and the material of the guide wire. When the region behind a guide wire is part of an intravascular brachytherapy target, the presence of the guide wire results in a significant underdosing for beta sources. The underdosed region can extend a few mm behind the guide wire and up to 1 mm in other directions. CONCLUSION: Significant dose perturbations by the presence of a metallic guide wire have been found in catheter-based intravascular brachytherapy using beta sources. The dose effects should be considered in the dose prescription and/or in analyzing the treatment outcome for beta sources. Such precautions are not necessary if using a gamma source.

Beta versus gamma for catheter-based intravascular brachytherapy: dosimetric perspectives in the presence of metallic stents and calcified plaques.

PURPOSE: Both beta and gamma emitters are currently used in the catheter-based intravascular brachytherapy. The dosimetric effects due to the presence of metallic stents and calcified plaques have not been fully addressed. This work compares these effects for two most commonly used beta and gamma sources ( (90)Sr and (192)Ir). MATERIALS AND METHODS: An EGS4 Monte Carlo package was used to calculate dose in water for a (90)Sr (supplied by NOVOSTE) and an (192)Ir (Supplied by BEST) source, with or without the presence of a calcified plaque or a metallic stent. Plaques of different shape (shell and disk), size and density, and two types of stainless-steel stents (ring or mesh stent) were studied. The ring stent consists of identical rings stacked along the long axis of the sources. The gap between two rings is 0.3 mm. The mesh stents are made of identical square (0.1 x 0.1 or 0.2 x 0.2 mm(2)) holes separated from each other by stainless-steel wire. The cross section of wire for both ring and mesh stents is 0.1 x 0.1 mm(2). A dose perturbation factor (DPF), defined as the ratio of the doses with and without the presence of a plaque or a stent, was introduced to quantify the effects. A carefully chosen set of EGS4 transport parameters for the small geometry in question was used in the calculation. RESULTS: The radial and axial dose distributions calculated in water were found to agree with the published measurements to within 3%. The dose perturbations due to the presence of calcified plaques or metallic stents were found far more significant for the (90)Sr source than those for the (192)Ir source. Up to 30% dose reduction behind a plaque were observed for the (90)Sr source, while the dose reduction for the (192)Ir source was found to be negligible. The dose enhancement inside a plaque was as high as 10% for the beta source or 6% for the gamma source. In the presence of a stent, the DPF was in the range of 1.15-0.75 for the beta source, while it was almost equal to 1.0 for the gamma source. CONCLUSION: The dose perturbation due to the presence of a calcified plaque or a metallic stent is significant for the beta source. The dose reduction in the region beyond a plaque or a stent could be more than 20%. For the gamma source, the dose effect behind a plaque or a stent is practically negligible. These dosimetric differences between the beta and gamma sources in the presence of a calcified plaque or metallic stent should be considered in the dose prescription of intravascular brachytherapy.

Inactivation of the MEK/ERK pathway in the myocardium during cardiopulmonary bypass.

OBJECTIVES: A general pro-inflammatory response after cardiopulmonary bypass (CPB) may involve changes in signal transduction and in part be responsible for arrhythmias and myocardial dysfunction after cardiac surgery. The MEK/ERK (mitogen-activated protein kinase kinase/extracellular regulated kinase) pathway is common to many stimuli and may play a pivotal role in morbidity associated with CPB. We investigated the changes in MEK/ERK pathway and related enzymes after CPB in pigs. METHODS: We examined ventricular and atrial tissue from pigs before 90 minutes of normothermic CPB and after 90 minutes of post-CPB perfusion. The activities and protein levels of kinases MEK1/2, ERK1/2, a cellular tyrosine kinase (c-Src), protein kinase B (Akt), and the protein levels of mitogen-activated protein kinase phosphatase (MKP-1) were studied by immunoblotting ventricular and atrial myocardium lysates and labeling sections with antibodies that recognize the activated forms of the kinases and the phosphatase. Control pigs were subjected to sternotomy and heparinization but not CPB. RESULTS: We found a consistent inactivation of MEK/ERK pathway in both ventricular and atrial myocardium with an increase in MKP-1, a negative regulator of ERK1/2. The activities and protein levels of c-Src and Akt were not significantly modified before or after CPB, suggesting a certain degree of specificity for the MEK/ERK pathway. Such changes were not observed in controls. The decrease of ERK1/2 and MEK1/2 phosphorylation 90 minutes after termination of CPB (as well as the increase of nuclear MKP-1 protein levels) was also apparent by confocal microscopy. CONCLUSIONS: These results collectively reveal a prevalence of inhibitory mechanisms in the MEK/ERK signal transduction machinery in myocardium subjected to CPB.

A case report of deficiency in an inhibitor of calcium-dependent association of protein S with C4B-binding protein suggested by a modified crossed immunoelectrophoresis.

We have experienced a coagulation factor VIII-deficient patient whose plasma has normal protein S (PS) activity and masses of free PS and its bound form in complex with C4b-binding protein (C4BP). Although the patient's plasma showed a normal ratio of free PS to PS-C4BP complex in the presence of 5 mM EDTA, the plasma gave an abnormally retarding major C4BP peak together with a major PS peak in the crossed immunoelectrophoresis (CIE) in the presence of 2 mM CaCl2. It was revealed that the major peak was formed by a mixture of PS-C4BP complex and free form. The addition of normal human plasma (NHP) to the patient's plasma inhibited the retardation of the major PS-C4BP complex. These suggest that the patient's plasma lacks some component(s) to inhibit Ca(2+)-dependent association of PS with C4BP.

Dosimetric effects of contrast media for catheter-based intravascular brachytherapy.

The purpose of this work is to calculate the dose perturbations due to the presence of iodine contrast media in catheter-based intravascular brachytherapy (IVBT). The EGSnrc Monte Carlo system was used to perform the calculation for the two most commonly used beta and gamma sources (90Sr and 192Ir as well as for a variety of monoenergetic photon and electron sources. Various contrast media with cylindrical-shell shapes were considered. The dose perturbations due to the presence of iodine contrast media were found to be significant for IVBT. In the region outside of the contrast media (usually the treatment target region for IVBT), the dose is generally increased for the gamma source, while it is decreased for the beta source. In the presence of a 1.0-mm-thick common clinical contrast medium, the dose enhancement can be as high as 30% for the 192Ir source, while the dose can be reduced by up to 25% for the 90Sr source. The dose enhancement region for the gamma source extends approximately 1.0 mm away from the contrast medium, while the dose reduction for the beta source affects the entire target region. The dose perturbation depends on (1) the volume (thickness) of the contrast medium, (2) the iodine concentration in contrast media, and (3) the type and energy of radioactive source. The dose effects due to the contrast medium as well as the differences between beta and gamma sources, revealed in this study, should be recognized and may be considered in the dose prescription for intravascular brachytherapy. These effects should also be taken into account in analyzing the treatment outcome for those IVBT clinical trials involving a contrast medium.