TGF-β1 Null Mutation Leads to CD154 Upregulated Expression in Affected Tissues

The TGF-1(–/–) mouse is a murine model for systemic autoimmune disease. The aim of this study is to elucidate the immunological mechanism that leads to multifocal tissue inflammation and autoantibody production in TGF-1(–/–) mice. Heart, lung, liver, and salivary gland from TGF-1(–/–) were assessed for CD154 expression by RT-PCR and immunohistochemistry. Compared to wild-type littermates, CD154 expression was elevated in all tissues studied. Furthermore, IL-12 mRNA was expressed in the salivary gland and heart of TGF-1(–/–) mice and not in wild-type littermates. This suggests that the CD154 pathway is activated in these tissues. This shows that TGF-1 regulates CD154 expression leading to spontaneous IL-12 production and autoimmunity.     

Diagnostic accuracy of multislice computed tomography coronary angiography is improved at low heart rates

Purpose: Assess the effect of heart rate on diagnostic accuracy for the detection of significant coronary artery stenosis using 16-row multislice computed tomography (MSCT). Material and methods: About 120 patients (105 males; 59±11 years) with suspected coronary artery disease who underwent conventional coronary angiography (CA) and MSCT-CA were retrospectively enrolled for the study. Patients underwent a MSCT-CA (Sensation 16, Siemens, Germany), with the following protocol: collimation 16×0.75 mm, gantry rotation time 420 ms, feed/rotation 3.0 mm, kV 120, mAs 400–500. The protocol for contrast material administration was 100 ml of Iodixanol (Visipaque 320 mg l/ml, Amersham, UK) at 4 ml/s and the delay was defined with a bolus tracking technique. In all patients the mean heart rate (HR) during the scan was used as a criteria to divide the population in two groups of 60 patients each. In one group (Low HR) the 60 patients with lower heart rates, and in the other group (High HR) the patients with higher heart rates. In the two groups diagnostic accuracy (per coronary segment) for the detection of significant stenosis (≥50% lumen reduction) was evaluated in vessels ≥2 mm of diameter using quantitative CA as reference standard. The difference in diagnostic accuracy were compared with a Chi² test and a p<0.05 was considered significant. Results: There was no significant difference between the two groups regarding age, gender, weight, mean intravascular attenuation, and calcium score. Overall 1310 (652 for Low HR and 658 for High HR) segments with 219 (105 for Low HR and 114 for High HR) significant lesions were available for the analysis. The average heart rate was 52±4HU and 63±5HU for Low HR and High HR, respectively (p<0.001). The sensitivity and specificity were 92 and 96% for Low HR and 90 and 92% for High HR (p<0.05). There were 22 vs. 44 false positives, and 8 vs. 12 false negatives in the Low HR and High HR, respectively. Conclusion: Increasing HR significantly deteriorates diagnostic accuracy in MSCT-CA.     

Brain conditioning is instrumental for successful microglia reconstitution following hematopoietic stem cell transplantation

The recent hypothesis that postnatal microglia are maintained independently of circulating monocytes by local precursors that colonize the brain before birth has relevant implications for the treatment of various neurological diseases, including lysosomal storage disorders (LSDs), for which hematopoietic cell transplantation (HCT) is applied to repopulate the recipient myeloid compartment, including microglia, with cells expressing the defective functional hydrolase. By studying wild-type and LSD mice at diverse time-points after HCT, we showed the occurrence of a short-term wave of brain infiltration by a fraction of the transplanted hematopoietic progenitors, independently from the administration of a preparatory regimen and from the presence of a disease state in the brain. However, only the use of a conditioning regimen capable of ablating functionally defined brain-resident myeloid precursors allowed turnover of microglia with the donor, mediated by local proliferation of early immigrants rather than entrance of mature cells from the circulation.     

Level of HER2/neu amplification in primary tumours and metastases in HER2-positive breast cancer and survival after trastuzumab therapy

BackgroundThe level of HER2/neu amplification may vary widely in breast cancers with HER2/neu alteration. The clinical significance of this phenomenon is still unclear. This study was aimed to explore the level of HER2/neu amplification in primary tumours and metastases in HER2-positive metastatic breast cancer (MBC) and its potential impact on survival after a trastuzumab-containing therapy.MethodsWe retrospectively identified MBC patients treated with a trastuzumab-containing therapy and performed dual-colour FISH on tumour samples from either primary tumour and/or metastasis in a central laboratory.ResultsWe retrieved 110 tumour samples from 91 patients and included 79 tumour samples (primary = 56; metastasis = 23) from 63 patients in the final analysis. We found higher level of HER2/neu amplification in the metastases than in the primary tumours (median HER2/CEP17 ratio: 10.5 vs 7.0, respectively). In 69% of patients (n = 16) with two tumour samples, the level of HER2/neu amplification was higher in the metastasis than in the paired primary tumour (median HER2/CEP17 ratio: 10.9 vs 8.3, respectively, p = 0.004). The incremental gain in level of HER2/neu amplification was associated with significantly shorter OS after trastuzumab-containing therapy (p = 0.023, HR 1.014, CI95%: 1.002–1.025).ConclusionsThe level of HER2/neu amplification tends to increase from the primary tumour to the paired metastases in a significant proportion of patients with HER2-positive MBC. This phenomenon, although still not completely understood, could lead to a shorter OS after trastuzumab therapy.     

Image assessment with multislice CT coronary angiography

AIM: To investigate the diagnostic accuracy of two different protocols for image evaluation used in multislice computed tomography coronary angiography (MSCT-CA). MATERIALS AND METHODS: Sixty patients with suspected coronary artery disease undergoing conventional coronary angiography (CA) were enrolled for MSCT-CA. All patients underwent 16-row MSCT (Sensation 16, Siemens, Germany) with the following parameters: detector rows 16, collimation 0.75 mm, gantry rotation time 375 ms. Two independent observers assessed the images for significant stenosis using a a protocol with standard projections and a three-dimensional protocol. The diagnostic accuracy for both methods was calculated using quantitative CA as a reference standard. RESULTS: The sensitivity, specificity, negative predictive value and positive predictive value obtained with the conventional projection protocol and with three-dimensional protocol were: 54% and 93%, 97% and 97%, 76% and 86%, 92% and 99%, respectively. CONCLUSIONS: Conventional projections in the assessment of MSCT-CA provide insufficient diagnostic accuracy compared with three-dimensional processing.     

End-to-End Ureteral Anastomosis: A Simple Alternative to Cutaneous Ureterostomy in Selected Patients

End-to-end of terminal ureteral segments seems to be a good alternative to terminal cutaneous ureterostomy in very selected cases (patients with short life-expectancy or when it is impossible to utilize the bowel for urinary diversion). Background: An end-to-end ureteral anastomosis (UA) drained by a single percutaneous nephrostomy is proposed as an alternative to permanent cutaneous ureterostomy. Methods: In eight patients who underwent radical cystectomy, an end-to-end UA was realized. All patients had an advanced pelvic neoplasm and/or severe comorbidities with a short life-expectancy. Results: End-to-end UA is a very simple intervention, well tolerated by the patient that requires only the periodic substitution of the nephrostomy. Conclusions: In very selected cases (patients with short life-expectancy, advanced disease) end-to-end UA is a quick and easy way to divert the urine after bladder removal.     

Technical analysis of volume-rendering algorithms: application in low-contrast structures using liver vascularisation as a model

AIM: To assess the influence of pre-set volume-rendering opacity curves (OC) on image quality and to identify which absolute parameters (density of aorta, hepatic parenchyma and portal vein) affect visualization of portal vascular structures (low-contrast structures). MATERIALS AND METHODS: Twenty-two patients underwent a dual-phase spiral CT with the following parameters: collimation 3 mm, pitch 2, increment 1 mm. Three scans were performed: one without contrast medium and the latter two after the injection of contrast material (conventionally identified as 'arterial' and 'portal'). The images were sent to a workstation running on an NT platform equipped with post-processing software allowing three-dimensional (3D) reconstructions to generate volume-rendered images of the vascular supply to the liver. Correlation between the absolute values of aorta, liver and portal vein density, OC parameters, and image quality were assessed. RESULTS: 3D images generated using pre-set OC obtained a much lower overall quality score than those produced with OC set by the operator. High contrast between the liver and the portal vein, for example during the portal vascular phase, allows wider windows, thus improving image quality. Conversely, the OC in the parenchymal phase scans must have a high gradient in order to better differentiate between the vascular structures and the surrounding hepatic parenchyma. CONCLUSIONS: Image features considered to be of interest by the operator cannot be simplified by the mean of pre-set OC. Due to their strong individual variability automatic 3D algorithms cannot be universally applied: they should be adapted to both image and patient characteristics.