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The gene expression profile of metastasizing serotonin-producing neuroendocrine carcinomas, which arise from enterochromaffin cells in the jejunum and ileum, is still largely unknown. The aim of this study was to identify genes and proteins, which are preferentially expressed by neuroendocrine carcinoma and enterochromaffin cells and therefore potential novel biomarkers and/or therapeutic targets. Six carcinoma specimens and six normal ileal mucosas were profiled by Affymetrix microarrays. Advanced bioinformatics identified differentially and specifically expressed genes, which were validated by quantitative real-time-PCR on tumor cells extracted by laser capture microdissection and normal enterochromaffin cells extracted by immunolaser capture microdissection. We identified six novel marker genes for neuroendocrine carcinoma cells: paraneoplastic antigen Ma2 (PNMA2), testican-1 precursor (SPOCK1), serpin A10 (SERPINA10), glutamate receptor ionotropic AMPA 2 (GRIA2), G protein-coupled receptor 112 (GPR112) and olfactory receptor family 51 subfamily E member 1 (OR51E1). GRIA2 is specifically expressed by neuroendocrine carcinoma cells whereas the others are also expressed by normal enterochromaffin cells. GPR112 and OR51E1 encode proteins associated with the plasma membrane and may therefore become targets for antibody-based diagnosis and therapy. Hierarchical clustering shows high similarity between primary lesions and liver metastases. However, chemokine C-X-C motif ligand 14 (CXCL14) and NK2 transcription factor related locus 3 Drosophila (NKX2-3) are expressed to a lower level in liver metastases than in primary tumors and normal enterochromaffin cells, which implies a role in neuroendocrine carcinoma differentiation. In conclusion, this study provides a list of genes, which possess relatively specific expression to enterochromaffin and neuroendocrine carcinoma cells and genes with differential expression between primary tumors and metastases. We verified six novel marker genes that may be developed as biomarkers and/or therapeutic targets.

Introduction: Our aim was to investigate the immune status of midgut carcinoid patients. Cancer patients generally display suppressed Th1-type immunity that disables mounting of an efficient anti-tumor response. However, little is known about patients with neuroendocrine midgut carcinoids., Material and Methods: Circulating regulatory T cells were determined in patient blood by staining for CD4, CD25 and FoxP3 in flow cytometric analysis. T cell proliferation was measured by Alamar Blue in response to polyclonal activation and the regulatory phenotype of patient CD25+ cells was validated by allogeneic stimulation of CFSE labelled responders. Cytokine levels in patient peripheral blood were measured by ELISA and CBA. Tumor infiltrating T cells were analyzed by immunohistochemistry and immunofluorescence., Results: The results demonstrate that midgut carcinoid patients exhibit increased frequencies of circulating Tregs and patient T cells have a decreased proliferative capacity compared to healthy donors. Systemic Th1-promoting cytokines are reduced. Midgut carcinoid tumors display CD4+ and CD8+ T cell infiltration, always in the presence of regulatory CD4+FoxP3+ cells., Discussion: Midgut carcinoid patients display elevated T regulatory cell numbers and T cell dysfunction. Therapeutic strategies to overcome tumor-induced Th1 immunosuppression are required in combination with anti-tumor vaccinations.

Purpose: The aim of the study was to identify immunogenic HLA-A*0201-binding epitopes derived from a number of classical midgut carcinoid-associated proteins. CD8(+) T cells recognizing tumor-associated antigen (TAA) epitopes are of great interest for the establishment of immunotherapy as a novel treatment for this type of malignancy., Experimental Design: Midgut carcinoid tumor specimens were microdissected and expression levels of potential TAAs were investigated by quantitative real time PCR. HLA-A*0201-binding motifs were selected using HLA peptide binding prediction algorithms and stabilization of HLA-A*0201 was verified using TAP-deficient T2 cells. Peripheral blood of midgut carcinoid patients was analyzed for peptide epitope recognition and the feasibility of generating peptide-reactive CD8(+) T cells in healthy blood donors was examined by an in vitro stimulation protocol using mature DCs. Activation of patient and healthy donor CD8(+) T cells was analyzed by intracellular flow cytometry staining of interferon gamma., Results: Chromogranin A (CGA), tryptophan hydroxylase 1 (TPH-1), vesicular monoamine transporter 1 (VMAT-1), caudal type homeobox transcription factor 2 (CDX-2), and islet autoantigen 2 (IA-2) are properly expressed by midgut carcinoid tumor cells, with CGA mRNA expressed to greatest level. Midgut carcinoid patients have increased frequencies of peripheral blood CD8(+) T cells recognizing a pool of HLA-A*0201 peptides derived from these proteins compared to healthy age-matched individuals. Activated peptide-specific CD8(+) T cells could also be generated in healthy blood donors by in vitro stimulation., Conclusion: We have identified a number of immunogenic midgut carcinoid-associated peptide epitopes recognized by CD8(+) T cells. We show that midgut carcinoid patients display immune recognition of their tumors. Memory CD8(+) T cells in patient blood are of great interest when pursuing an immunotherapeutic treatment strategy.

Purpose: The use of replication-selective oncolytic adenoviruses is an emerging therapeutic approach for cancer, which thus far has not been employed for carcinoids. We therefore constructed Ad[CgA-E1A], a novel replication-selective oncolytic adenovirus, where the chromogranin A (CgA) promoter controls expression of the adenoviral E1A gene., Experimental Design: The Ad[CgA-E1A] virus was evaluated for E1A protein expression, replication ability, and cytolytic activity in various cell lines. It was also evaluated for treatment of xenografted human carcinoid tumors in nude mice. To use Ad[CgA-E1A] for the treatment of carcinoid liver metastases, it is important that normal hepatocytes do not support virus replication to minimize hepatotoxicity. We therefore evaluated CgA protein expression in normal hepatocytes. We also evaluated CgA gene expression in normal hepatocytes and microdissected tumor cells from carcinoid metastases., Results: We found that Ad[CgA-E1A] replicates similarly to wild-type virus in tumor cells with neuroendocrine features, including the BON carcinoid cell line and the SH-SY-5Y neuroblastoma cell lines, whereas it is attenuated in other cell types. Thus, cells where the CgA promoter is active are selectively killed. We also found that Ad[CgA-E1A] is able to suppress fast-growing human BON carcinoid tumors in nude mice. Furthermore, CgA is highly expressed in microdissected cells from carcinoid metastases, whereas it is not expressed in normal hepatocytes., Conclusion: Ad[CgA-E1A] is an interesting agent for the treatment of carcinoid liver metastases in conjunction with standard therapy for these malignancies.

Classical midgut carcinoids are serotonin-secreting tumors derived from enterochromaffin cells in the gut. Metastatic disease represents a therapeutic challenge and immunotherapy implies a novel approach for treatment. In order to define antigens suitable for T-cell therapy with a preferential expression in midgut carcinoid tissue a broad screening of genes with preferential neuroendocrine restriction, genes described as over-expressed in various malignancies, and genes encoding cancer-testis associated antigens was performed. The expression of 32 genes was analyzed by reverse transcription polymerase chain reaction (RT-PCR) in 28 midgut carcinoid specimens, in the cell line BON and in normal tissues. Immunohistochemistry (IHC) was used to evaluate protein expression. Expression is shown of genes that have previously not been observed in midgut carcinoid tumors, such as Survivin and GAGEs. Also the expression is confirmed of genes that encode pivotal proteins in enterochromaffin cells, such as TPH1 and VMAT1, and their tissue-restricted expression is indicated. In addition, gene expression of IA-2 and CDX-2 in normal gastrointestinal (GI) tract and in tumor is shown. Protein expression of TPH, VMAT1, and Survivin was detected in tumor tissue. This study elucidates that TPH1, VMAT1, and Survivin should be further investigated as potential target antigens for T cell-mediated immunotherapy of midgut carcinoids.

TARP (T cell receptor gamma-chain alternate reading frame protein) is uniquely expressed in males in prostate epithelial cells and prostate cancer cells. Here we demonstrate that TARP expression is regulated by testosterone at the transcriptional level through specific binding of androgen receptor to an androgen response element in the proximal TARP promoter. We further demonstrate that the promoter specifically initiates reporter gene expression in TARP-positive prostate cancer cell lines. To develop a regulatory sequence for prostate-specific gene expression, we constructed a chimeric sequence consisting of the TARP promoter and the prostate-specific antigen (PSA) enhancer. We found that in the prostatic adenocarcinoma cell line LNCaP, the transcriptional activity of the regulatory sequence consisting of a TARP promoter and PSA enhancer is 20 times higher than the activity of a regulatory sequence consisting of the PSA promoter and PSA enhancer. Thus, our studies define a regulatory sequence that may be used to restrict expression of therapeutic genes to prostate cancer cells and may therefore play a role in prostate cancer gene therapy.

Members of the SREBP family of transcription factors control cholesterol and lipid homeostasis and play important roles during adipocyte differentiation. The transcriptional activity of SREBPs is dependent on the coactivators p300 and CBP. We now present evidence that SREBPs are acetylated by the intrinsic acetyltransferase activity of p300 and CBP. In SREBP1a, the acetylated lysine residue resides in the DNA-binding domain of the protein. Coexpression with p300 dramatically increases the expression of both SREBP1a and SREBP2, and this effect is dependent on the acetyltransferase activity of p300, indicating that acetylation of SREBPs regulates their stability. Indeed, acetylation or mutation of the acetylated lysine residue in SREBP1a stabilizes the protein. We demonstrate that the acetylated residue in SREBP1a is also targeted by ubiquitination and that acetylation inhibits this process. Thus, our studies define acetylation-dependent stabilization of transcription factors as a novel mechanism for coactivators to regulate gene expression.

Retinyl ester concentration is regulated by retinoic acid (RA) through an autoregulatory loop, which acts on lecithin:retinol acyltransferase (LRAT). We tested whether retinol esterification activity is downregulated in human mammary carcinoma cells and whether LRAT expression is RAR-regulated. Normal human mammary epithelial (HMEC) cells expressed a retinoid-upregulated 5-kb LRAT transcript and synthesized retinyl esters from 3H-retinol. Human carcinoma MCF-7 cells failed to express the 5-kb LRAT transcript and to synthesize retinyl esters. Instead, they expressed a 2.7-kb LRAT transcript. Both transcripts were upregulated by RA. Stable expression of the dominant-negative RARalpha403 blunted the up-regulation of LRAT mRNA by RA. We conclude that retinol esterification is decreased in MCF-7 vs normal mammary cells; that these cancer cells express a shorter (2.7 kb) LRAT transcript, and that retinoid receptors are involved in the regulation of LRAT-mediated retinyl ester synthesis by RA.

Interferon regulatory factor 1 (IRF-1) transcription factor binds to DNA sequence elements found in the promoters of type I IFN and IFN-inducible genes. Transient up-regulation of the IRF-1 gene by virus and IFN treatment causes the consequent induction of many IFN-inducible genes involved in cell growth control and apoptosis. We reported recently that IFN-alpha and all-trans retinoic Acid (RA) inhibit the cell proliferation of squamous carcinoma cell line ME-180 by inducing apoptotic cell death. IRF-1 expression correlates with the IFN-alpha-induced apoptosis phenomenon and, surprisingly, with the RA-induced apoptosis phenomenon. To study how these two different ligands cross-talk in the regulation of cellular antitumor responses, the signalling pathways involved in IRF-1 induction were analyzed in RA and/or IFN-alpha-treated ME-180 cells. We provide evidence indicating that RA-induced IRF-1 gene expression is independent of the STAT-1 activation pathway, despite the presence of the IFN-gamma activated sequence element in the gene promoter, but involves nuclear factor-kappaB activation. Thus, here we first describe the activation of nuclear factor-kappaB by both IFN-alpha and RA in the ME-180 cell line. The induced IRF-1 protein is successively able to bind the IFN-stimulated responsive element in the promoter of the target gene 2',5'-oligoadenylate synthetase.

Retinoic acid (RA)-resistant cell lines are highly malignant. To inhibit the growth of the RA-resistant cells we used 4-HPR, a synthetic retinoid, which may act through alternative signal transduction pathways. 4-HPR induced cell growth inhibition and apoptosis in all RA-sensitive as well as -resistant cells, demonstrating a wider spectrum of potency over RA. 4-HPR induced tissue TGase activity. A tight correlation between the induction of tissue TGase, the inhibition of cell growth, and apoptosis was evident in all eight RA-sensitive cell lines. However, basal TGase differed in the different cells, suggesting inducibility rather than basal levels as the relevant parameter. In sharp contrast to the RA-sensitive cells, RA-resistant cells showed sporadic response to 4-HPR for tissue TGase. The wider spectrum of activity of 4-HPR in inhibiting cell growth and inducing apoptosis makes it a good candidate for the treatment of RA-resistant cancer cells.

Recent studies have revealed promising leads on the potential of interferons (IFNs) in combination with retinoids in solid tumor therapy. The role of IFN-alpha and retinoic acid (RA) in cervical cancer is currently under active study. Because preclinical and clinical data on IFN-beta in combination with retinoids show promising results against breast carcinoma, we analysed the anti-proliferative effect of human recombinant IFN-beta alone or in combination with all-trans RA on two human squamous cervical carcinoma cell (SCC) lines (ME180 and SiHa). The two cell lines differ in their sensitivity to the anti-proliferative effects of the different agents and their combination: i) both cell lines were more responsive to IFN-beta than to IFN-alpha2b; ii) combined treatment with RA increases the growth inhibitory effect of the single agents in ME180, but not in SiHa; iii) the antiproliferative effect correlates with the induction of apoptosis. We suggest as a possible mechanisms of action that interferon regulatory factor-1 (IRF-1), a transcription factor which belongs to the IFN machinery, and the cyclin-dependent kinase inhibitor (CDKi) p21 can be involved in cellular growth inhibition and in the induction of apoptosis. These results support the use of IFN-beta in further clinical investigation possibly in combination with retinoids.

Several lines of evidence have demonstrated that IFNs could be relevant in the treatment of certain neoplastic diseases such as carcinomas. In particular, IFN-alpha, in addition to the anti-proliferative and cytostatic effects, was demonstrated to be capable of inducing cell death by apoptosis both in vivo and in vitro. Numerous protocols have also been proposed which consider the association of IFN-alpha with other drugs. Among these are retinoids, a class of compounds capable of inducing inhibition of cell growth and differentiation. We address the question here by analyzing the role of cell adhesion in susceptibility to IFN-alpha, RA and their combination of a human cell line derived from a squamous carcinoma of the cervix, the Bcl-2-negative SiHa cell line. In this context, cytoskeleton components and several surface molecules playing a role in cell substrate and cell-to-cell relationships have been evaluated. We found that RA treatment is capable of improving stress fiber formation, decreasing cell detachment and increasing cell-adhesion capability. However, no variations in the ability to adhere to specific extracellular-matrix molecules were found in RA-treated cells. No quantitative changes were detected in integrins involved as receptors for extracellular matrix molecules (VLAI-VLA5) or in other cell-adhesion-associated molecules (e.g., CD44). By contrast, 2 important molecules involved in cell-adhesion processes appeared to be up-regulated by RA exposure: focal adhesion kinase and E-cadherin, involved in adhesion plaque formation and cell-to-cell contacts, respectively. Keeping in mind the importance of adhesion properties in the cell-growth pathway, our findings could be of interest in the study of carcinoma-cell proliferation and metastatic potential.

Both retinoids and IFNs are known to inhibit proliferation of many normal and transformed cells and to have an in vivo antitumor effect against a variety of cancers, including squamous cell carcinoma. Because the combination of IFNs and all-trans retinoic acid (RA) could improve their antitumor effectiveness (depending on the histological origin and state of differentiation of the cells), we compared the activity of RA and/or IFN-alpha 2b with regard to the mechanism of growth inhibition of ME180 and SiHa cell lines, derived from squamous cervix carcinoma at different stages of differentiation. We reported previously that, in the ME180 cell line, the combined treatment significantly increased the growth inhibitory effect of the single agents. Here, we show that the SiHa cell line appears more sensitive to IFN-alpha 2b than the ME180 cell line, and resistant to RA, which does not significantly inhibit SiHa cell growth. Induction of apoptotic cell death clearly occurs and correlates with the inhibition of cell proliferation in both cell lines. It is interesting that the induction of the transcription factor IFN regulatory factor 1 correlates with the subsequent induction of apoptosis, whereas TGase I and II expression does not. In particular, TGase I and II appear differentially expressed in the ME180 and SiHa cell lines; i.e., TGase I is expressed in ME180 and specifically inhibited by RA, whereas TGase II is expressed in SiHa. It is interesting that both IFN-alpha and RA are able to increase TGase II expression and activity in this cell line.

The in vivo and in vitro antitumor effectiveness of IFNs is well documented. Their combination with differentiating agents, such as retinoic acid, has been demonstrated to be a promising therapy for patients with advanced squamous cell cancer of the skin and the cervix. However, the mechanisms that mediate these antitumor responses are not yet known. We studied the epidermoid cell line ME 180 derived from human cervical carcinoma to test its responsiveness to IFN-alpha-2b (INTRON A) and all-trans-retinoic acid (RA). Both agents have demonstrated ability to inhibit the growth of ME 180 cells in a dose- and time-dependent manner. The antiproliferative effect was further increased by the treatment with IFN-alpha-2b and RA combined. In accordance with this result, we found that the combination of the two agents has the effect of increasing the expression of the 2-5A synthetase gene, which is thought to play a key role in antigrowth responses to IFNs. At increased levels of 2-5A synthetase mRNA corresponds a significant increase in 2-5A synthetase activity. Although RA per se has no effect on the 2-5A synthetase expression, when it is combined with IFN-alpha-2b it appears to be able to potentiate the IFN-induced 2-5A synthetase expression. Moreover, the combination of IFN-alpha-2b and RA produces a similar effect also on the expression of the HLA-A2 gene, which has been shown to be induced in ME 180 cells both by IFN-alpha-2b and RA alone. In view of the possible mechanisms of action of the two agents, it is interesting to note that their combination increases, although transiently, the expression of IRF1, which codes for a transcription factor that regulates IFN gene expression and is thought to be involved in the regulation of IFN-induced effects and in mediating cell death or apoptosis.

This study was aimed at assessing the diagnostic value of a new intravenous contrast agent SH U 508 A (Levovist) in improving color Doppler detection of renal mass vascularity. The study included 30 patients with renal masses: 22 adenocarcinomas, 1 sarcoma, 1 leiomyosarcoma, 1 urothelioma, 1 hemorrhagic cyst and 4 angiomyolipomas. The vascularization of the renal masses was investigated by means of color Doppler US, before and after the intravenous injection of SH U 508 A (Levovist), on the basis of blood flow patterns within and around the lesions. At precontrast scanning, low color Doppler signal at the periphery or within the lesions was observed in 13/30 patients only. After contrast administration, the signal-to-noise ratio increased, which allowed the visualization of tumor vessels in 26/30 patients. In 4/30 patients only no major enhancement of tumor vessels was observed. Our experience suggests that SH U 508 A (Levovist) improves color Doppler sensitivity in depicting the tumor vessels which were missed at baseline exams and in evaluating renal vein and inferior vena cava involvement.

The reproducibility of hepatic blood flow measurement with pulsed Doppler US was assessed in 6 healthy volunteers. All subjects underwent two different study sessions and were examined by three different operators after overnight fasting. Each operator was blind to his measurements. Hepatic arterial and portal venous blood flow and hepatic arterial maximum velocity were measured; resistive index (RI), pulsatility index (PI) and hepatic perfusion index (HPI) were calculated. Each measurement was repeated three times per session. The data from repeated measurements were analyzed with the analysis of variance (ANOVA) method to assess the intra- and intersubject variations for each variable. The Scheffe test was used to evaluate intra- and interobserver variations. Significant differences among the 6 examined subjects were found for all the variables measured, except for hepatic arterial maximum velocity. The same subject exhibited significant differences in mean velocity of the main portal vein trunk and of its right branch, in maximum hepatic arterial velocity, RI, portal vein section area and blood flow. No significant interobserver variation was observed in the same session and no intraobserver variation detected for all the measurements performed in different sessions. Thus, we conclude that pulsed Doppler US is a repeatable method for measuring hepatic blood flow and may therefore be useful to detect changes in hepatic perfusion.

The reproducibility of ultrasound measurements of the pancreas was investigated in 10 healthy volunteers. All subjects underwent three different evaluations, each consisting of three ultrasound examinations, at 8:00 after overnight fasting, at 12:00 after a solid, standard meal, and at 14:00. The longitudinal and anteroposterior (AP) diameters of the head, body, and tail, as well as the total areas of the gland, were measured in longitudinal and axial scans. Significant differences were observed in the head and body longitudinal diameters measured at 12:00 and in the tail AP diameter at 14:00. We conclude that ultrasonography of the pancreas should be performed in the morning with patients in the fasting state. In these conditions, the reliability of ultrasound measurements of the gland appears to be the highest.

The differential diagnosis of peripelvic cysts and hydronephrosis by means of US sometimes presents some problems; in fact, the use of urography to solve a diagnostic doubt is not uncommon. This study was aimed at demonstrating that another US sign, which we have called the "convexity" sign, can be useful in allowing peripelvic cysts to be distinguished from hydronephrosis. Thus, cysts exhibit convex walls and curved outline, whereas in hydronephrosis the walls of the dilated calices are linear. The latter feature is present in all degrees of hydronephrosis, except in severe cases. Forty-nine adult patients, a total of 98 kidneys, were examined with US and urography; 69 kidneys were found to be pathologic: 48 presented with cysts, and 21 with hydronephrosis. In addition to the new sign, the classic signs of peripelvic cysts were also considered, that is the separate areas and the non-visualization of the ureter. The sensitivity of the new sign was 97% and its specificity was 95%. The sensitivity and the specificity of the classic signs were 97% and 95%, respectively for the separated areas, and 100% and 91% for the non-visualization of the ureter. The cumulative sensitivity of the 3 signs was 99%, and their specificity 96%. Our results show how the integrated analysis of the considered signs (especially those with high specificity) is useful for the differential diagnosis, and therefore to avoid the indiscriminate use of urography.

Aim of this study was to determine whether pancreatic size is altered in patients suffering from type I diabetes mellitus. Twenty-five diabetics (14 males and 11 females) and twenty-five healthy controls entered the study. All patients and controls were scanned by the same operator with the same US equipment after overnight fasting. The longitudinal and antero-posterior diameters of the head, body and tail and the transverse diameter of the head as well as the total area of the gland were measured through longitudinal and axial scans. The two groups were homogeneous relative to age, sex, distribution, height, weight and body mass index. All measured diameters as well as the total area of the gland were significantly smaller in diabetic patients than in controls (1-way ANOVA: p less than 0.001). These results may open new perspectives to US identification of possible changes in pancreatic size by a new US study including high-risk subjects without clinical signs.

The authors report their experience with US of the hip in 1000 children aged 1 day to 8 months. US study was carried out following Graf's method. All the children were previously examined by a pediatrician, who recorded all the clinical signs on a chart. After US examination, the radiologist recorded US findings on the same chart. Thus, US findings could be compared to clinical ones: there was agreement in 71% of cases, and disagreement in the extant 29%. Furthermore, clinics exhibited a high false-negative rate (64%) and a low false-positive rate (23%). This suggests US as an useful screening method able to show early morphological and functional alterations in the infant hip. The authors also examined the incidence of the single clinical signs and risk factors, and correlated them with US findings.

The authors report their experience with the combined use of US and CT in the study of diffuse and subtotal fatty infiltration of the liver. An apparent disagreement was initially found between the two examinations in the study of fatty infiltration. Fifty-five patients were studied with US and CT of the upper abdomen, as suggested by clinics. US showed normal liver echogenicity in 30 patients and diffuse increased echogenicity (bright liver) in 25 cases. In 5 patients with bright liver, US demonstrated a solitary hypoechoic area, appearing as a "skip area", in the quadrate lobe. In 2 patients with bright liver, the hypoechoic area was seen in the right lobe and exhibited no typical US features of "skip area". Bright liver was quantified by measuring CT density of both liver and spleen. The relative attenuation values of spleen and liver were compared on plain and enhanced CT scans. In 5 cases with a hypoechoic area in the right lobe, CT findings were suggestive of hemangioma. A good correlation was found between bright liver and CT attenuation values, which decrease with increasing fat content of the liver. Moreover, CT attenuation values confirmed US findings in the study of typical "skip areas", by demonstrating normal density--which suggests that CT can characterize normal tissue in atypical "skip areas".

The same radiologist, on 839 patients who were to be subjected to urography, did also preliminary ultrasonography in order to have at his disposal a greater amount of informations than those furnished by a simple abdominal X-ray. The clinical-radiological integration with such a procedure gains significance; consequently the succeeding urographic phases can be better arranged so as to improve their aim and purpose.

The authors report their experience with US of the hip in 200 children aged 9 days to 8 months. All the children previously were under-gone physical examination. The sonographic study was carried out with Graf's method. The clinical-sonographic correlation proves the utility of US as a screening method able to show early morphological and functional alterations in the hip. US is thus suggested as a valid alternative to conventional methods to use in those cases where either plastering or surgery is required.

The authors have examined 57 cases of thoracic pathology by conventional radiology, ultrasounds and computed tomography (CT). The conventional radiology remains the test of first choice; the ultrasounds proved sometimes useful to distinguish between solid and cystic lesions while CT is the method in the evaluation of the extension.

The authors, after mentioning physiologic appearance of portal circulation and physical principles governing the interrelationship of pressure, flow and flow velocity in blood vessels, report the results of a study about trend of haemodynamic values in 23 normal subjects and 13 cirrhotic patients. Values of portal blood flow and fluid speed were measured using a pulsed "Linear-Doppler" system, before and after dinner. Statistical analysis of results proves the diagnostic value of examination that appears qualified as the method of first choice in the patients with suspected changes of portal circulation.