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Biomedical subjects

C Nicolau

Publications and source records attributed to C Nicolau.

At least 19 recordsLinked to original sources
PubMed2006

Characterization of focal liver lesions: comparative study of contrast-enhanced ultrasound versus spiral computed tomography.

The purpose of this study was to compare the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) with spiral computed tomography (SCT) for the characterization of focal liver lesions (FLL) and to determine the degree of correlation between the two techniques. Seventy-seven FLL (45 hepatocellular carcinomas; 12 metastases; ten hemangiomas; two regenerating/dysplastic nodules; eight focal nodular hyperplasias) detected with ultrasound (US) were prospectively evaluated by CEUS using a second-generation contrast agent and SCT (with an interval of no more than one month between the two techniques). Independent observers made the most probable diagnosis and the results were compared with the final diagnoses (histology n = 59; MRI n = 18). Statistical analysis was performed by the Chi-square and Kappa tests. CEUS provided a correct, specific diagnosis in 69/77 (90%) of the FLL, while SCT did so in 67/77 (87%). The sensitivity, specificity, and diagnostic accuracy for malignancy were 91%, 90%, and 91%, respectively, for CEUS and 88%, 89%, and 88%, respectively, for SCT. No statistically significant difference was found between CEUS and SCT in the characterization of FLL (p > 0.05). In addition, agreement between the two imaging techniques was good (k = 0.75). We conclude that CEUS and SCT provide a similar diagnostic accuracy in the characterization of FLL, with a good degree of correlation between the two techniques.

Contrast Media↗
PubMed2006

Is microbubble-enhanced ultrasonography sufficient for assessment of response to percutaneous treatment in patients with early hepatocellular carcinoma?

The objective of this study was to assess the efficacy of contrast-enhanced ultrasonography (CEUS) with SonoVue to evaluate the response to percutaneous treatment (ethanol injection/radiofrequency) of hepatocellular carcinoma in comparison with spiral computed tomography (CT) immediately and 1 month after treatment. Forty-one consecutive cirrhotic patients with early stage tumor (not suitable for resection) were included. Spiral CT and CEUS were performed in all patients before treatment, in the following 24 h, and 1 month later. The results of each examination were compared with the 1-month spiral CT, considered the gold standard technique. The 24-h CEUS and the 24-h spiral CT sensitivity to detect residual disease were 27% and 20%, respectively. The 24-h CEUS and the 24-h spiral CT positive predictive value of persistent vascularization detection were 75% and 66%, respectively. The 1-month CEUS detected partial responses in ten out of 11 cases (91% sensitivity, 97% specificity, 95% accuracy). Spiral CT and CEUS performed in the 24 h following treatment are slightly useful to evaluate therapeutic efficacy. The 1-month CEUS has a high diagnostic accuracy compared with spiral-CT in the usual assessment of percutaneous treatment response.

Administration, Cutaneous↗
PubMed2006

[Living donor kidney transplantation: helical CT evaluation of candidates].

OBJECTIVES: Computed tomography (CT) is a diagnostic tool that has won acceptance in the past years for the vascular evaluation of living renal donor (LRD) candidates. We show the findings observed in a series of 102 candidates consecutively evaluated in our centre and present the correlation with the surgical data obtained in those individuals finally operated. METHODS: From May 1995 to June 2005, 102 LRD candidates were evaluated with CT. Eighteen were also studied with digital subtraction angiography (DSA). Fifty-eight donors underwent nephrectomy. Prevalence of arterial and venous variants found on CT exams were analyzed, as well as the correlation with surgical and DSA data when they were obtained. RESULTS: Forty-four percent candidates showed multiple renal arteries at least in one kidney. Seventy-one percent of right kidneys and 76% of left kidneys had a single arterial pedicle. Early branching was observed in 7.8% and 15.7% in right and left kidneys respectively. Venous variants were present in 17.5% and the 13.7% in right and left sides respectively. Sensitivity, specificity and accuracy of CT to detect accessory arteries were 89%, 100% and 97% respectively when it was compared to DSA. Correlation with surgical data raised 93% for the presence of arterial variants. CONCLUSIONS: Vascular variants in renal pedicle showed a high prevalence. Helical CT can effectively achieve all the information required prior to surgery as a sole imaging procedure in LRD candidates.

Humans↗
PubMed2004

The use of contrast-enhanced ultrasound in the management of the cirrhotic patient and for detection of HCC.

Hepatocellular carcinoma (HCC) is the leading cause of death in liver cirrhosis. Ultrasound (US) is widely accepted as the screening imaging modality of choice for HCC in patients with a history of chronic liver disease. However, the US characteristics of HCCs are non-specific and thus, other imaging techniques or biopsy are usually necessary to characterize focal liver lesions (FLL) and confirm malignancy. Blood flow to HCC is mainly arterial, making dynamic CT and MRI the most commonly used techniques to detect the characteristic arterial hypervascularization. Recently, the development of second-generation US contrast agents and microbubble-specific software has changed the role of US in real-time evaluation of the macro and microvascularization of FLLs. With this technology, the accuracy of US in the diagnosis of HCC and its differentiation from other FLLs such as regenerating nodules has improved dramatically. In addition, contrast-enhanced ultrasound may also be a useful tool in the staging of HCC and in the evaluation of percutaneous treatment.

Aged↗
PubMed2004

Inhibition of multidrug resistance by immunisation with synthetic P-glycoprotein-derived peptides.

Overexpression of the membrane glycoprotein (P170) represents the most common multidrug resistance (MDR) mechanism in cancer therapy. Specific auto-antibodies to extracellular loops 1, 2 and 4 of murine P170 were elicited in mice using palmitoylated synthetic peptides reconstituted in liposomes, with or without Lipid A, and resuspended in alum. IgM antibodies were detected 14 days following the first injection and IgG1 became predominant after the third challenge. Animals did not show any auto-immune symptoms or induced toxicity up to 18 months after the immunisation. Previous immunisations of mice using liposomes with MDR1 peptides increases the efficacy of chemotherapy treatments with doxorubicin and vinblastine against P388 R cells with increase of 77% in the survival half time in the immunised group. Sera from the immunised mice were also effective in reducing cellular resistance to vinblastine and doxorubicin in vitro. Taken together, these data suggest that this immunisation approach might have potential clinical applications.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2001

Intradermal delivery of interleukin-12 plasmid DNA by in vivo electroporation.

Gene therapy depends on safe and efficient gene delivery. The skin is an attractive target for gene delivery because of its accessibility. Recently, in vivo electroporation has been shown to enhance expression after injection of plasmid DNA. In this study, we examined the use of electroporation to deliver plasmid DNA to cells of the skin in order to demonstrate that localized delivery can result in increased serum concentrations of a specific protein. Intradermal injection of a plasmid encoding luciferase resulted in low levels of expression. However, when injection was combined with electroporation, expression was significantly increased. When performing this procedure with a plasmid encoding interleukin-12, the induced serum concentrations of gamma-interferon were as much as 10 fold higher when electroporation was used. The results presented here demonstrate that electroporation can be used to augment the efficiency of direct injection of plasmid DNA to skin.

Animals↗
PubMed2001

Early detection of hepatic artery thrombosis after liver transplantation by Doppler ultrasonography: prognostic implications.

We assessed the usefulness of routine Doppler ultrasonography for early detection of hepatic artery thrombosis after orthotopic liver transplantation and repercussions in patient prognosis. Seventeen confirmed cases of early hepatic artery thrombosis initially diagnosed by Doppler ultrasonography (10 of them before clinical indication) were reviewed. All patients underwent Doppler ultrasonographic studies in the first 3 days after orthotopic liver transplantation. Twelve cases of hepatic artery thrombosis (70.6%) were detected by this early Doppler ultrasonography. All 10 unsuspected cases of hepatic artery thrombosis and 5 of the 7 cases diagnosed after clinical indication were treated by revascularization. Grafts were salvaged in 80% of asymptomatic patients and in 42.8% of symptomatic patients. Furthermore, biliary complications were less serious in the first group. In conclusion, Doppler ultrasonography performed routinely in the first 3 days after orthotopic liver transplantation may permit early detection of hepatic artery thrombosis, even before clinical indications. This allows hepatic artery repermeabilization before liver function damage, improving graft rescue and patient prognosis.

Adolescent↗
PubMed2001

Effect of internal carotid artery occlusion on vertebral artery blood flow: a duplex ultrasonographic evaluation.

The aim of this study was to evaluate the effect of unilateral internal carotid artery occlusion on blood flow volume and blood flow velocities in both vertebral arteries using duplex Doppler ultrasonography in the cervical segment. Forty patients with unilateral extracranial internal carotid artery occlusion confirmed by angiography were studied, and the results were compared with those obtained in 57 age-matched patients in whom cervical duplex ultrasonography showed no abnormalities. We measured the diameter, flow velocities, and blood flow volume in both vertebral arteries, and the side-to-side differences were also calculated. Eleven patients (27.5%) with an occluded internal carotid artery had increased peak systolic velocity in the ipsilateral vertebral artery, and 6 (15%) had increased peak systolic velocity in the contralateral vertebral artery. The mean peak systolic velocity and the mean blood flow volume were statistically greater in the ipsilateral vertebral arteries than in the same-side vertebral arteries of the control group (P < .05). We also detected a mean increase of 14.29% of the net blood flow volume in the vertebral arteries compared with the control group. Patients with extracranial unilateral internal carotid artery occlusion may have a compensatory increase in both the peak systolic velocity and the blood flow volume in both vertebral arteries.

Aged↗
PubMed2000

Increased prevalence of polycystic kidney disease type 2 among elderly polycystic patients.

Autosomal dominant polycystic kidney disease (ADPKD) is genetically heterogeneous, with at least three chromosomal loci (PKD1, PKD2, and PKD3) accounting for the disease. Mutations in the PKD2 gene, on the long arm of chromosome 4, are estimated to be responsible for 15% of the cases of ADPKD, based on linkage studies. PKD2 is a milder form of the disease, with a mean age of end-stage renal disease (ESRD) approximately 20 years later than PKD1. The object of this study is to determine the proportion of elderly patients with ADPKD with ESRD who harbor mutations in the PKD2 gene. We analyzed all exons and intron-exon boundaries of the PKD2 gene by single-strand conformation polymorphism analysis and silver staining technique in 46 patients with ADPKD who reached ESRD after the age of 63 years or were not yet undergoing renal replacement therapy (RRT) by that age. We performed exactly the same studies in a control group of 40 patients with ADPKD with unknown gene status aged younger than 63 years. In 22 patients, a mutation in the PKD2 gene was defined: 18 of 46 patients from the elderly group and 4 of 40 patients from the control group. We identified 14 different mutations: 4 nonsense mutations, 1 missense mutation, 5 small deletions, 2 insertions, 1 deletion of the whole PKD2 gene, and 1 splicing mutation. Five of these mutations previously were described by our group. Three of the mutations reported in the present study are recurrent. The prevalence of PKD2 disease among elderly patients with ADPKD undergoing RRT is 39.1%, almost three times the prevalence of the disease in the general ADPKD population.

Adult↗
PubMed2000

Sonographic pattern of recessive polycystic kidney disease in young adults. Differences from the dominant form.

BACKGROUND: To study the sonographic pattern of autosomal recessive polycystic kidney disease (ARPKD) in early adulthood in order to identify imaging criteria to diagnose this disease and to distinguish between recessive and autosomal dominant polycystic kidney disease (ADPKD) in that age group. METHODS: An abdominal ultrasound was performed on four ARPKD subjects (with a mean age of 20.2) and on 33 ADPKD subjects in early adulthood (29 without renal failure with a mean age of 20.5, and four with renal failure with a mean age of 26.5). Linkage studies with ADPKD and ARPKD markers were compatible with the clinical diagnosis in all cases. RESULTS: The renal sonographic features in ARPKD subjects included multiple small cysts in a normal-sized kidney, increased cortical echogenicity and loss of corticomedullary differentiation. In ADPKD subjects without renal failure, sonographic features included few or multiple cysts of different sizes, in normal-sized kidneys in 22 out of 29 patients (75.8%), normal cortical echogenicity and conserved corticomedullary differentiation, except in patients with nephromegaly. All ADPKD subjects with renal failure had nephromegaly and loss of corticomedullary differentiation. The hepatic sonographic features in ARPKD patients included portal fibrosis and in some cases Caroli's disease, while in ADPKD patients a normal hepatic echostructure was detected in all but one case, in addition to simple hepatic cysts in a few cases. CONCLUSIONS: The evaluation of the sonographic features of the kidneys and those of the liver may help in the differential diagnosis between ARPKD and ADPKD in early adulthood.

Adult↗
PubMed2000

Doppler sonography of the intertransverse segment of the vertebral artery.

We assessed the utility of a Doppler ultrasonographic examination of the vertebral artery, limited to the intertransverse segment, in diagnosis of disease at any level of vertebrobasilar circulation. The vertebral artery was identified in all the patients, with a successful evaluation of the presence of disease in 112 of 116 (96.5%) vertebral arteries. All of the occlusions and subclavian steal syndromes were diagnosed. All of the vertebral arteries with abnormal Doppler findings had a pathologic angiographic study. In conclusion, Doppler ultrasonography of the intertransverse segment of the vertebral artery is useful owing to its applicability and accuracy.

Aged↗
PubMed1999

In vivo gene delivery by electroporation.

The physical phenomenon of electroporation has been successfully exploited in vitro for the delivery of genes, drugs, and other molecules with increasing frequency over the past two decades. This type of electrically mediated delivery has been translated into an in vivo setting in more recent years with a focus on therapeutic molecules. One promising area is the delivery of genes as a therapy.Advances in molecular medicine have produced a very large amount of information about genes that translate to therapeutic molecules when expressed in living cells. Current standard methods for transferring genes utilize viruses to deliver DNA into cells. These viral methods have not yielded optimal results in most cases. Therefore, there is an increasing interest in nonviral methods for gene delivery. In vivo electrically mediated gene delivery is an attractive alternative because of the site specific nature of delivery as well as the universal applicability of electroporation. A review of the studies performed to investigate and develop this new gene delivery technology is presented.

Journal Article↗
PubMed1999

Autosomal dominant polycystic kidney disease types 1 and 2: assessment of US sensitivity for diagnosis.

PURPOSE: To estimate the sensitivity and specificity of ultrasonography (US) in the diagnosis of autosomal dominant polycystic kidney disease (ADPKD) types 1 and 2, as compared with those of genetic linkage analysis. MATERIALS AND METHODS: A renal US and DNA analysis for ADPKD was performed in 319 patients who were at risk, 161 of whom were younger than 30 years, from 54 families with ADPKD. The sensitivity of US for diagnosis was estimated by comparing the US results with genotypes inferred from linkage studies. RESULTS: The sensitivity of US in individuals younger than 30 years who were at risk was 95% for ADPKD type 1 but only 67% for ADPKD type 2. The sensitivity of US for either ADPKD type 1 or ADPKD type 2 in individuals aged 30 years or older who were at risk was 100%. The overall sensitivity in individuals younger than 30 years was 93%. For both ADPKD types 1 and 2 in all patients, US demonstrated a sensitivity of 97%, a specificity of 100%, and an accuracy of 98%. CONCLUSION: US is the first-line imaging technique that should be used in the diagnosis of ADPKD. The sensitivity in individuals aged 30 years or older is 100%, but if there is a clinical suspicion of ADPKD type 2 in individuals younger than 30 years, linkage analysis should also be considered.

Adolescent↗
PubMed1998

[Clinical, genetic and molecular studies on autosomal dominant polycystic kidney disease].

BACKGROUND: Two genes causing autosomal dominant polycystic kidney disease (ADPKD), PKD1 and PKD2, have been described. In the present work we study, by means of linkage analysis, the genetic heterogeneity in our population as well as the clinical differences between PKD1 and PKD2. SUBJECTS AND METHODS: 316 subjects belonging to 49 unrelated ADPKD families have been studied by means of 3 microsatellites for PKD1 and 3 for PKD2 to differentiate if they have ADPKD type 1 or 2. The techniques used to analyze the microsatellites have been the chemiluminescence and the silver satining techniques. All the subjects underwent a complete physical examination and a sonographic scan. Clinical and molecular results have been correlated. RESULTS: Genetic heterogeneity has been proved, with 85% of families linked to PKD1 and 15% to PKD2. The disease is more severe in PKD1, with an earlier age at diagnosis (27.4 vs. 41.4 years; p = 0.0002), a younger age at the onset of end stage renal disease (53.4 vs. 72.7 years, p < 0.00001), and earlier age at diagnosis of hypertension (34.8 vs. 49.7 years; p = 0.001) and a higher prevalence of hypertension for all groups of age. In both forms of ADPKD there were families showing anticipation (8/44 for PKD1 and 2/5 for PKD2) but this was not a widespread phenomenon. Our data do not support the phenomenon of genetic imprinting for this disease. CONCLUSION: In the population of Catalonia, Spain, PKD1 accounts for 85% of families with autosomal dominant polycystic kidney disease and PKD2 accounts for the remaining 15%. PKD1 form is more severe than PKD2.

Adult↗
PubMed1997

Immunotargeting of liposomes to activated vascular endothelial cells: a strategy for site-selective delivery in the cardiovascular system.

Endothelial-selective delivery of therapeutic agents, such as drugs or genes, would provide a useful tool for modifying vascular function in various disease states. A potential molecular target for such delivery is E-selectin, an endothelial-specific cell surface molecule expressed at sites of activation in vivo and inducible in cultured human umbilical vein endothelial cells (HUVEC) by treatment with cytokines such as recombinant human interleukin 1beta (IL-1beta). Liposomes of various types (classical, sterically stabilized, cationic, pH-sensitive), each conjugated with mAb H18/7, a murine monoclonal antibody that recognizes the extracellular domain of E-selectin, bound selectively and specifically to IL-1beta-activated HUVEC at levels up to 275-fold higher than to unactivated HUVEC. E-selectin-targeted immunoliposomes appeared in acidic, perinuclear vesicles 2-4 hr after binding to the cell surface, consistent with internalization via the endosome/lysosome pathway. Activated HUVEC incubated with E-selectin-targeted immunoliposomes, loaded with the cytotoxic agent doxorubicin, exhibited significantly decreased cell survival, whereas unactivated HUVEC were unaffected by such treatment. These results demonstrate the feasibility of exploiting cell surface activation markers for the endothelial-selective delivery of biologically active agents via immunoliposomes. Application of this targeting approach in vivo may lead to novel therapeutic strategies in the treatment of cardiovascular disease.

Cardiovascular Diseases↗
PubMed1997

Immunological approach to hepatocellular carcinoma.

A library of monoclonal antibodies (MoAbs) has been produced against a human hepatocellular carcinoma (HCC) cell line designated FOCUS in order to study the antigenic properties of transformed hepatocytes. Several monoclonal antibodies (MoAbs) were initially selected for study since they bound to antigens which were overexpressed in HCC tissues compared with the adjacent uninvolved normal liver counterpart; in addition, these MoAbs revealed low level antigen expression on other normal human tissues. Subsequently, HCC cell lines were metabolically labelled and the antigens further characterized by immunoprecipitation and Western blot analysis. If the MoAb recognized a primary linear epitope on a protein, cloning was performed using a lambda GT11 cDNA expression library prepared from the FOCUS HCC cell line. These studies characterized the HCC associated antigen(s) at the molecular level. This review illustrates the value of such an experimental approach to search for and identify HCC associated antigens and emphasizes the biological properties of novel proteins may be defined and characterized by these techniques. More important, our investigations have described unique proteins that may not only be important in the pathogenesis of HCC but also demonstrates how such antigen-antibody systems may be used to develop strategies for immunotargetting and gene therapy of HCC.

Animals↗