Beyond C4d: Other Complement-Related Diagnostic Approaches to Antibody-Mediated Rejection

Complement is a multifunctional system of receptors and regulators as well as effector molecules. Both the pathogenic and diagnostic power of complement is based on the capacity of the complement system to amplify innate and adaptive immunity. This amplification is accomplished through two strategies: (1) enzymatic reactions in the complement cascade, and (2) stimulation of leukocytes, platelets and parenchymal cells through specific receptors or receptor-independent pore formation. The mechanisms by which complement mediates and modifies nonspecific inflammation, antibody-mediated injury and T-cell responses are of particular significance to the pathogenesis of transplant rejection. Understanding the mechanisms by which complement integrates the interactions of leukocytes, platelets and parenchymal cells offers opportunities to further refine the diagnosis of rejection.     

Ventilation imaging of the lung: Comparison of hyperpolarized helium-3 MR imaging with Xe-133 scintigraphy

RATIONALE AND OBJECTIVES: To compare hyperpolarized helium-3 (HHe) magnetic resonance imaging (MRI) of the lung with standard Xe-133 lung ventilation scintigraphy. MATERIALS AND METHODS: We performed a retrospective review of 15 subjects who underwent HHe MRI and Xe-133 lung ventilation imaging. Coronal MRI sections were acquired after a single inhalation of HHe gas, and standard posterior planar lung ventilation scintigraphy was performed during continuous breathing of Xe-133 gas. The first breath scintigram of each patient was compared with a composite MR image composed of the sum of the individual MR images and with the individual helium-3 MR images. Ventilation defects on the two imaging modalities were compared for size, conspicuity, and concordance in presence and location. Assessment was done separately for each of four lung quadrants. RESULTS: Comparing the composite HHe MR images with Xe-133 scintigraphy, ventilation defect size, conspicuity and concordance were the same in 67% (40/60), 63% (38/60), and 62% (37/60) quadrants, respectively. Comparing the individual HHe MR image sections with the Xe-133 ventilation scan, there was concordance between the ventilation defects in 27% (16/60) of quadrants. More defects were identified on the individual HHe MR images in 62% (37/60) of quadrants. CONCLUSION: There was good agreement between composite HHe MR image and first breath Xe-133 scintigraphic images, supporting the widely held assumption that HHe MRI likely depicts first breath lung ventilation.     

Sonography as a training tool for screening of dubious midfacial fractures]

BACKGROUND: In uncertain midfacial fractures, sonography is an alternative first-line imaging modality to conventional radiographs. Patients with sonographically confirmed fractures can then be directly admitted to three-dimensional imaging, resulting in decreased radiation exposure since the conventional radiographs are omitted. MATERIAL AND METHODS: Using a high-frequency linear and curved array scanner in a healthy proband, images of the zygomatic arch, anterior maxillary sinus wall, infraorbital rim, and lateral orbital wall were obtained. For identification and anatomical allocation corresponding navigated ultrasound images of a reference skull were generated and fused with a segmented CT data set. Navigated sonography was reproduced in a patient with orbitozygomatical fracture of the left side. Therefore, the CT data set, performed during preoperative diagnostics, was fused with the ultrasound images. RESULTS: Because of different coupling shapes, the high-frequency linear array scanner was subjectively found to be more suitable for sonography in the field of the zygomatic arch, anterior maxillary sinus wall, and infraorbital rim, and the curved array scanner was better suited for transbulbar sonography of the orbital walls. After coupling sonography with the navigation system and referencing the scanner, it was possible to verify ultrasound findings objectively by navigation of the scanner and fusion with the CT data set. Using the reference skull, ultrasound images corresponding to normal findings were obtained and with the fused CT data, providing colored segmentation of the facial bones, an anatomically correct identification was possible. Clinical application of this tool is described in a patient with left-sided orbitozygomatical fracture. CONCLUSION: By fusion of ultrasound images and corresponding CT data with the help of a navigation system, a sonographic training tool for preliminary evaluation of midfacial fractures is available.     

Endometrial stromal neoplasms are immunoreactive with WT-1 antibody.

WT-1 positivity has previously been noted in nonneoplastic endometrial stroma. In this study we examined WT-1 expression in endometrial stromal neoplasms to ascertain whether these tumors are immunoreactive and whether this antibody might be of value in the diagnosis of these lesions. We also stained cases of cellular and highly cellular leiomyomas to investigate whether WT-1 might be of value in distinguishing these from an endometrial stromal neoplasm. We compared WT-1 staining with CD10, desmin, alpha smooth muscle actin, h-caldesmon, and AE1/3, many of these antibodies being commonly used to distinguish between an endometrial stromal and a smooth muscle phenotype. Cases of ESN (n = 5), low grade ESS (n = 14), and cellular or highly cellular leiomyoma (n = 14) were stained with the aforementioned antibodies. Cases were scored on a scale of 0 to 4+, with 4+ cases exhibiting positivity of >50% of cells. Sixteen of 19 endometrial stromal neoplasms were positive with WT-1, most (14 of 16) with 4+ positivity. Staining was nuclear (5 cases), cytoplasmic (5 cases), or combined nuclear and cytoplasmic (6 cases). All endometrial stromal neoplasms exhibited 4+ staining with CD10. Staining for alpha smooth muscle actin was present in most cases (14 of 19) and desmin and h-caldesmon were positive in a smaller number of cases (8 and 2 respectively). There was 4+ positivity with desmin in only 1 case. The 2 cases that were h-caldesmon positive both exhibited 1+ staining (<5% cells positive). Six cases were positive with AE1/3, 1 with 4+ staining. Leiomyomatous neoplasms always exhibited 4+ staining with desmin and alpha smooth muscle actin and in most cases (12 of 14) with h-caldesmon. The other 2 cases exhibited 2+ positivity. Most cases (12 of 14) were positive with WT-1 (7 of 14 with 4+ staining) and CD10 (5 of 14 with 4+ positivity). One case was positive with AE1/3. We conclude that diffuse WT-1 positivity is characteristic of endometrial stromal neoplasms and that this may be of value in diagnosis. However, WT-1 is of limited use in the distinction between an endometrial stromal and a cellular leiomyomatous neoplasm because many of the latter are also positive. This study confirms the value of h-caldesmon in the distinction between an endometrial stromal neoplasm (almost always h-caldesmon negative) and a cellular leiomyomatous neoplasm (h-caldesmon positive). Although CD10 is positive in endometrial stromal neoplasms, the commonly observed immunoreactivity of cellular and highly cellular leiomyomas with this antibody limits its diagnostic usefulness. Desmin is useful as all leiomyomatous neoplasms exhibited diffuse positivity, whereas only a small number of endometrial stromal neoplasms were focally positive and only 1 case exhibited 4+ positivity. Smooth muscle actin is of limited value since most neoplasms studied were positive. The overlapping immunophenotype of endometrial stromal and leiomyomatous neoplasms may reflect the origin of both cell types from a common progenitor within the uterus.     

Effects of periodic weight support in a simulated weightless environment in preventing bone demineralisation.

Anti Orthostatic Hypokinetic posture in rats by tail suspension for 15 days (d) simulates the deconditioning effects of weightlessness on the weight bearing bones. The present study evaluates the effects of daily 4 hour (h) weight support (WS) during simulated weightlessness (S-W) in preventing these changes. Adult male albino rats were divided into three groups as (i) Control (CON, n = 12), (ii) Hind limb unweighing by tail suspension for 15 d (HU, n = 18), (iii) HU with daily 4 h WS (4 HRWS, n = 11). After 15 d tibia from all the animals were removed and subsequently dried, ashed and then calcium content of the bones were determined. HU showed reductions in the water content by 35.8%, organic matrix by 12.2% and calcium content by 33.4% of tibia. 4 h WS during S-W resulted in complete prevention of water loss and organic matrix loss and partial prevention of the loss of calcium content. Calcium content of tibia in 4 HRWS remained 15.2% less as compared to CON. These findings indicate that 4 h WS is partially successful in preventing the demineralisation effects of S-W on weight bearing bone tibia.     

Preparation of bupivacaine-loaded poly(epsilon-caprolactone) microspheres by spray drying: drug release studies and biocompatibility.

Poly(epsilon-caprolactone) microspheres containing bupivacaine were prepared by the spray-drying process. The average size of drug loaded microspheres was less than 3 microm in diameter, and the percentage of entrapment efficiency was 91 +/- 3%. In vitro drug release kinetic in phosphate buffer at 37 degrees C showed a hyperbolic profile, with a burst-effect during the first hour. Subcutaneous injection of bupivacaine-loaded microspheres in the back of rats caused an increase in drug concentration in plasma. Maximum bupivacaine concentration in plasma was 237 +/- 58 ng/ml at 105 h, and drug was detected in plasma for 16 days. The half-life time of the drug was increased by more than 125 times with regard to that of the drug administered in a solution by intraperitoneal injection. After 30 days of injection, a mass formed by microspheres surrounded by a thin fibrous capsule was observed. Small blood vessels and multinucleate foreign body giant cells with macrophagic function around microspheres were detected. After 60 days of injection a subcutaneous mass was also observed, which was formed of more degraded dispersed microspheres in conjunctive tissue, which had a normal structure. Thus, bupivacaine-loaded poly(epsilon-caprolactone) microspheres could be considered as a device to be used in the treatment of severe pain that is not responsive to opioids for example in cancer-related syndromes or in intractable herpetic neuralgia.