Low dose CTPA using a low kV technique combined with high IR: A clinical study.

INTRODUCTION: To investigate optimising a computerised tomography pulmonary angiogram (CTPA) scan protocol in terms of radiation dose and image quality using a low kV technique combined with high iterative reconstruction (IR) parameters (>50%) and apply the optimised protocol in clinical practice on patients irrespective of their body weight. METHODS: CTPA examinations were performed on 64 patients equally divided into control and experimental groups. Patients in the control group were scanned using the current protocol (100 kV with 50% IR) while patients in the experimental group were scanned using an optimised protocol (80 kV with 60%IR). The radiation dose indices volume computerised tomography dose index (CTDIvol), dose length product (DLP), size specific dose estimates (SSDE) and effective dose (ED) were recorded. Subjective image quality was evaluated by 3 radiologists through absolute visual grading analysis (VGA) using an image quality scoring tool. The resultant image quality scores were analysed using Visual Grading Characteristics (VGC). Objective image quality was recorded in terms of contrast-to-noise-ratio (CNR) and signal-to-noise-ratio (SNR). RESULTS: The application of the optimised protocol resulted in a statistically significant (p < 0.05) reduction in mean CTDIvol (-49%), DLP (-48%), SSDE (-52%) and ED (-49%). Objective image quality was significantly (p < 0.05) improved both in CNR (32%) and SNR (13%). Subjective image quality scores were higher for the current protocol but variation between the two protocols was not significant (p = 0.650). CONCLUSIONS: When applying the low kV technique combined with high IR parameters, a significant dose reduction may be achieved while still maintaining diagnostic image quality. IMPLICATIONS FOR PRACTICE: The low kV technique combined with high IR parameters is an effective optimisation technique which can be easily implemented for the CTPA protocol.

Optimisation of the CT pulmonary angiogram (CTPA) protocol using a low kV technique combined with high iterative reconstruction (IR): A phantom study.

INTRODUCTION: This study aims to optimise the current CTPA protocol at a public general hospital in Malta using lower kV combined with high Iterative Reconstruction (IR) (>50%). METHODS: The research consisted of a 2-phase anthropomorphic phantom study. Phase 1: radiation dose evaluation of 6 experimental protocols consisting of the low kV technique and high IR values and comparison with the current protocol. Phase 2: image evaluation. Objective image quality was evaluated in terms of contrast to noise ratio (CNR) and signal to noise ratio (SNR). Subjective image quality evaluation was performed by 3 radiologists undertaking Absolute Visual Grading Analysis (VGA). Resultant image quality scores were analysed using Visual Grading Characteristics (VGC). RESULTS: All experimental protocols achieved significant (p < 0.05) dose reductions. SNR and CNR improved in almost all protocols, however, differences were not significant (p > 0.05). In subjective image quality analysis, the current protocol provided significant superior image quality (AUC > 0.5; p < 0.05) when compared to the experimental protocols consisting of 80 kV with 70%, 80%, 90% and 100% IR. The only two experimental protocols yielding comparable image quality to the current protocol were 80 kV with 50% IR (AUC: 0.195; p: 0.137) and 80 kV with 60% IR (AUC: 0.554; p: 0.624). The protocol yielding the greatest decrease in radiation dose being 80 kV with 60% IR. CONCLUSIONS: The optimal IR value was 60%. When applying the optimal experimental protocol (80 kV combined with 60% IR), a significant dose reduction was achieved while maintaining diagnostic image quality. IMPLICATIONS FOR PRACTICE: The low kV technique combined with high IR parameter is easily implemented and involves no additional cost and equipment.

Human polyomavirus JC reactivation and pathogenetic mechanisms of progressive multifocal leukoencephalopathy and cancer in the era of monoclonal antibody therapies.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the neurotropic human polyomavirus JC (JCV) lytic infection of oligodendrocytes. PML was first described as a complication of lymphoproliferative disorders more than 50 years ago and emerged as a major complication of human immunodeficiency virus (HIV) infection in the 1980s. Despite the ubiquity of this virus, PML is rare and always seen in association with underlying immunosuppressive condition, such as HIV infection, autoimmune diseases, cancer, and organ transplantation. JCV remains quiescent in the kidneys, where it displays a stable archetypal non-coding control region (NCCR). Conversely, rearranged JCV NCCR, including tandem repeat patterns found in the brain of PML patients, have been associated with neurovirulence. The specific site and mechanism of JCV NCCR transformation is unknown. According to one model, during the course of immunosuppression, JCV departs from its latent state and after entering the brain, productively infects and destroys oligodendrocytes. Although the majority of PML cases occur in severely immunesuppressed individuals, PML has been increasingly diagnosed in patients treated with biological therapies such as monoclonal antibodies (mAbs) that modulate immune system functions: in fact, CD4+ and CD8+ T lymphopenia, resulting from this immunomodulatory therapy, are the primary risk factor. Furthermore, JCV reactivation in nonpermissive cells after treatment with mAbs, such as intestinal epithelial cells in Crohn's disease patients, in association with other host tumor-inducing factors, could provide valid information on the role of JCV in several malignancies, such as colorectal cancer.

Antibacterial activity of methyl aminolevulinate photodynamic therapy in the treatment of a cutaneous ulcer.

We describe a 79-year-old female with a chronic venous ulceration infected by Staphylococcus aureus and Enterococcus faecalis and not responsive to conventional treatments. The patient was treated with Methyl-Aminolaevulinate Photodynamic Therapy (MAL-PDT). After four weeks the cutaneous swabs become negative and we observed a significant clinical improvement. Therefore we suppose that MALPDT could represent a valid therapeutic option in the treatment of infected chronic ulcers.

JC Viral reactivation in a pediatric patient with Crohn's disease.

This is a report concerning human polyomavirus JC (JCV) reactivation in a pediatric patient with Crohn's disease (CD) during the treatment with 5-aminosalicylic acid (5-ASA), a non-steroidal anti-inflammatory drug (NSAID). We examined 9 bioptic samples from three different bowel districts (ileum, cecum, rectum) of this child. These samples were analyzed by Quantitative PCR (Q-PCR) to investigate the presence of JCV DNA. JCV DNA was detected in one rectum biopsy taken two months after 5-ASA treatment. Although our result must be validated in a larger group of subjects and with a longer follow-up period, it underlines the importance of JVC monitoring in CD patients.

Optimisation of the lateral lumbar spine projection using an air-gap technique.

INTRODUCTION: Lumbar spine radiography is considered as having a high radiation dose compared to other planar radiography examinations. The aim of this study was to investigate the feasibility of replacing an antiscatter grid with an air gap technique to achieve dose reduction for lateral lumbar spine radiography while maintaining image quality on a direct digital radiography (DDR) system. METHODS: In phase 1, an experimental study using an anthropomorphic phantom identified the optimal airgap technique. In phase 2, lateral projections of the lumbar spine were performed on 50 patients randomly assigned equally into a control group (using the antiscatter grid) and an experimental group (using the airgap technique). The dose area product (DAP) was recorded, keeping other variables constant. Image quality evaluation was performed by 5 radiologists performing Absolute Visual Grading Analysis (VGA) using an image quality score tool, with resultant scores analysed using Visual Grading Characteristics (VGC). RESULTS: A 10 cm airgap in conjunction with a source to image distance (SID) of 121 cm was found as the optimal airgap technique. The clinical application of this technique resulted in a statistically significant (p < 0.05) reduction in DAP of 72%. Image quality scores were higher for the antiscatter grid but variation between the two techniques was not significant (p > 0.05). CONCLUSION: Replacing the antiscatter grid with an airgap technique in lateral lumbar spine digital radiography, provides a significant dose reduction whilst still maintaining diagnostic image quality. IMPLICATIONS FOR PRACTICE: The airgap technique is a simple and easy technique to implement and radiographers should find no difficulties in applying it, as It involves no additional cost and no additional equipment.

A case of human polyomavirus Bk infection in a patient affected by late stage prostate cancer: could viral infection be correlated with cancer progression?

The basic molecular mechanisms regulating prostate cancer (PCA) development and progression are very poorly understood. Different tumor suppressor genes are implicated in PCA. In particular, since the mutation rate of the p53 gene is also low, researchers have speculated that an infectious agent might play an important role in PCA. Polyomaviruses are candidates for this agent. We selected a patient with a diagnosis of PCA and underwent radical prostatectomy, to investigate the presence of polyomavirus BK (BKV) sequences (urine and neoplastic tissues) and the mutation pattern of p53 gene. The results obtained showed the presence of BKV DNA and of p53 gene mutations in exons 6, 8 and 9. We speculate that BKV might contribute to cellular transformation process, triggered possibly by p53 gene mutations.

TGF-beta1 and IGF-1 expression are differently regulated by serum in metastatic and non-metastatic human breast cancer cells.

Transforming growth factor-beta (TGF-beta) exerts an inhibitory effect on epithelial cell proliferation while insulin-like growth factor-1 (IGF-1) is a positive regulator of proliferation and together they may participate in driving neoplastic progression. The regulation of TGF-beta1 and IGF-1 gene expression was analyzed in an in vitro model of an estrogen receptor positive (ER+), non-metastatic (MCF-7) and an (ER-), metastatic (MDA-MB-435) breast cancer cell line, respectively. Our results indicate a loss of the regulation of TGF-beta1 and the gain of the expression and upregulation of IGF-1 pathways during malignant progression. These data demonstrate that two factors, convergent on cell growth, can have divergent roles in the regulation of the expression of TGF-beta1.

[CEA in the follow-up of breast carcinoma]. / Il CEA nel follow-up del carcinoma mammario.

One of the dominant aspects of cancer research over the past 10-15 years has been the search for a specific, sensitive marker for the various cancer types and one with a high predictive value. The importance and frequency of breast cancer, the demanding follow-up required in mastectomised patients and the fact that mammary carcinoma responds quite well to therapy with a fairly good survival rate as long as metastases and recurrences are promptly identified and treated encouraged this investigation into the value of CEA as a tumour marker in the follow-up of breast cancer. The problem was to discover whether. CEA would prove prompter than traditional investigations in identifying the appearance of recurrences or metastases or the increase of existing metastases and whether it provided a reliable indicator of the course of the disease and its response to treatment. Analysis of the results obtained in a personal series provided a negative answer to the first question and a positive one to the second. It is therefore concluded that only a well-planned and comprehensive follow-up, making use of all radiological, instrumental, laboratory and clinical aids will prove of any real benefit to mastectomised patients.

[Short- and long-term evaluation of treatment of critical ischemia of the lower lim with PGE1 (alprostadyl alpha-cyclodestrine)]. / Valutazione a breve e lungo termine del trattamento con PGE1 (alprostadil alpha-ciclodestrina) nell'ischemia critica degli arti inferiori.

Twenty-five patients affected by chronic lower limb obliterating arteriopathy with critical ischemia in one limb were treated with PGE1 for 4 weeks and then followed-up for one year. On day 14 of treatment three groups of patients were selected on the basis of clinical symptoms and instrumental tests; patients were subdivided into Responders, Partial Responders and Non-Responders. The results obtained were satisfactory in view of the fact that the selection into three groups enabled Partial Responders to be reclassified, in some cases by repeating the treatment cycle.

Polyomavirus BK infection in end-stage renal disease: analysis of viral replication in patients on hemodialysis or peritoneal dialysis.

Patients in end-stage renal disease undergoing renal replacement treatment (ESRD-RRT) are considered immunocompromised. The hemodialysis (HD) or peritoneal dialysis (PD) procedures seem to produce alterations of the immune status. Interest in immunosuppression has increased due to the poliomavirus BK (BKV) infection. Our study evaluated the prevalence of BKV infection in ESRD-RRT patients and viral replication on HD or PD. From 2006 to 2011 we selected 58 patients (34 males) in ESRD-RRT for inclusion in our study. BKV replication was evaluated by qualitative real-time polymerase chain reaction. In ESRD-RRT patients, the prevalence of BKV replication on plasma was 21%. We identified two groups of patients according to the dialysis procedure: 36 patients on HD (HD group) and 22 on PD (PD group). BKV replication in the HD group was 33% (12 of 36) versus 0% (0 of 22) in the PD group. Different age, number of months on RRT, and preserved diuresis was observed in the HD versus PD groups. With our results we can speculate that BKV infection in ESRD-RRT patients is linked to factors involved in the uremia-related immune dysfunction but also to specific mechanisms related to the different RRTs. PD is an option that could be associated with a better transplant outcome for patients undergoing kidney transplantation.

Polyomavirus BK infection before liver transplantation in patients with chronic kidney disease.

End-stage liver disease (ESLD) and chronic kidney disease (CKD) patients are both immunocompromised populations but polyomavirus BK (BKV) replication before liver transplantation is rare. We evaluated BKV prevalence among liver transplant recipients with renal dysfunction and the possible role of CKD as a risk factor for BKV replication in ESLD. From 2010 to 2011 we selected 31 ESLD patients awaiting liver transplantation to identify, the presence of CKD: No CKD (n = 22; 18 males) and CKD group (n = 9; 5 males). BKV infection was defined on the basis of viremia evaluated using quantitative real-time polymerase chain reactions. The prevalence of viremia among the No CKD group was 14% versus 56% in the CKD group (Fisher test; P = .027). We hypothesized that the presence of CKD may represent an additional condition of immunologic dysfunction regarding antiviral surveillances other than the antibacterial one that characterizes ESLD immunodysfunction, which could have promoted BKV replication. The specific immunologic mechanisms involved in pretransplantation diseases may have a role in BKV reactivation that could become responsible for nephropathy after transplantation.

Additive protection against lung ischemia-reperfusion injury by adenosine A2A receptor activation before procurement and during reperfusion.

OBJECTIVE: Adenosine A2A receptor activation during reperfusion improves lung ischemia-reperfusion injury. In this study we sought to determine whether pretreatment of rabbits with a potent and selective adenosine A2A receptor agonist, ATL-313, before transplantation or whether adding ATL-313 to the preservation solution results in equivalent or additional protection compared with ATL-313 added during reperfusion. METHODS: An isolated, ventilated, ex vivo blood-perfused rabbit lung model was used. All groups underwent 2 hours of reperfusion after 18 hours of cold ischemia (4 degrees C). ATL-313 was administered 1 hour before ischemia intravenously, with the preservation solution, and/or during reperfusion. RESULTS: Both pretreatment of donor animals with ATL-313 or adding ATL-313 just during reperfusion improved pulmonary function, but significantly greater improvement was observed when pretreatment and treatment during reperfusion were combined (all P < .05). Myeloperoxidase levels, bronchoalveolar lavage tumor necrosis factor alpha levels, and pulmonary edema were all maximally decreased in the combined treatment group. The administration of an equimolar amount of the potent and highly selective adenosine 2A receptor antagonist, ZM 241385, along with ATL-313, resulted in the loss of protection conferred by ATL-313. CONCLUSIONS: Adenosine A2A receptor activation with ATL-313 results in the greatest protection against lung ischemia-reperfusion injury when given before ischemia and during reperfusion. Improved pulmonary function observed with adenosine A2A receptor activation was correlated with decreased bronchoalveolar lavage tumor necrosis factor alpha and decreased lung myeloperoxidase. The loss of protection observed with the concurrent administration of the adenosine A2A receptor antagonist, ZM 241385, supports that the mechanism of ATL-313 protection is specifically mediated via adenosine A2A receptor activation.

An unusual clinical and biochemical presentation of ornithine transcarbamylase deficiency in a male patient.

We report a male patient with a history of recurrent idiopathic vomiting, normal plasma ammonia and glutamine concentrations in acute phase, who died at 3 years of age. Ornithine transcarbamylase deficiency was diagnosed after detecting elevated urinary orotate concentrations in a sample collected just before death, and the diagnosis was confirmed by DNA analysis.

Phosphoinositide 3-kinase is involved in the tumor-specific activation of human breast cancer cell Na(+)/H(+) exchange, motility, and invasion induced by serum deprivation.

Whereas the tumor acidic extracellular pH plays a crucial role in the invasive process, the mechanism(s) behind this acidification, especially in low nutrient conditions, are unclear. The regulation of the Na(+)/H(+) exchanger (NHE) and invasion by serum deprivation were studied in a series of breast epithelial cell lines representing progression from non-tumor to highly metastatic cells. Whereas serum deprivation reduced lactate production in all three cells lines, it inhibited NHE activity in the non-tumor cells and stimulated it in the tumor cells with a larger stimulation in the metastatic cells. The stimulation of NHE in the tumor cell lines was the result of an increased affinity of the internal H(+) regulatory site of the NHE without changes in sodium kinetics or expression. Serum deprivation conferred increased cell motility and invasive ability that were abrogated by specific inhibition of the NHE. Inhibition of phosphoinositide 3-kinase by overexpression of a dominant-negative mutant or wortmannin incubation inhibited NHE activity and invasion in serum replete conditions while potentiating the serum deprivation-dependent activation of the NHE and invasion. These results indicate that the up-regulation of the NHE by a phosphoinositide 3-kinase-dependent mechanism plays an essential role in increased tumor cell invasion induced by serum deprivation.

Na+/H+ exchanger-dependent intracellular alkalinization is an early event in malignant transformation and plays an essential role in the development of subsequent transformation-associated phenotypes.

In this study we investigate the mechanism of intracellular pH change and its role in malignant transformation using the E7 oncogene of human papillomavirus type 16 (HPV16). Infecting NIH3T3 cells with recombinant retroviruses expressing the HPV16 E7 or a transformation deficient mutant we show that alkalinization is transformation specific. In NIH3T3 cells in which transformation can be turned on and followed by induction of the HPV16 E7 oncogene expression, we demonstrate that cytoplasmic alkalinization is an early event and was driven by stimulation of Na+/H+ exchanger activity via an increase in the affinity of the intracellular NHE-1 proton regulatory site. Annulment of the E7-induced cytoplasmic alkalinization by specific inhibition of the NHE-1, acidification of culture medium, or clamping the pHi to nontransformed levels prevented the development of later transformed phenotypes such as increased growth rate, serum-independent growth, anchorage-independent growth, and glycolytic metabolism. These findings were verified in human keratinocytes (HPKIA), the natural host of HPV. Results from both NIH3T3 and HPKIA cells show that alkalinization acts on pathways that are independent of the E2F-mediated transcriptional activation of cell cycle regulator genes. Moreover, we show that the transformation-dependent increase in proliferation is independent of the concomitant stimulation of glycolysis. Finally, treatment of nude mice with the specific inhibitor of NHE-1, DMA, delayed the development of HPV16-keratinocyte tumors. Our data confirm that activation of the NHE-1 and resulting cellular alkalinization is a key mechanism in oncogenic transformation and is necessary for the development and maintenance of the transformed phenotype.