One-shot percutaneous ethanol injection of liver tumors under general anesthesia: Preliminary data on efficacy and complications

Purpose: To verify the efficacy of ultrasound (US)-guided injection of large amounts of ethanol into large or multiple liver lesions, in a single session under general anesthesia (one-shot PEI) for percutaneous ablation of hepatic tumors. Methods: Twenty-nine patients (27 with 51 hepatocellular carcinoma (HCC) nodules on cirrhosis, diameter range 1.0<+>–<+>9.0 cm; two patients with a single metastasis from the gastroenteric tract, 5.0 and 9.0 cm, respectively, in diameter) were treated with one-shot PEI. Results: The total volume of alcohol delivered per patient ranged from 16 to 210 ml. Mean ethanol volume in all patients was 49 ml. Dynamic computed tomography (CT) examination showed complete necrosis in 41 of 50 lesions. Two patients died of hypovolemic shock due to massive upper gastrointestinal bleeding, 3 and 7 days, respectively, after the interventional procedure. All the remaining patients are alive (follow-up 5<+>–<+>14 months) except one who died of liver failure 5 months after. New HCC nodules occurred in six patients within 6 months and one intralesional relapse was recorded. Conclusion: In this preliminary experience, one-shot PEI is as effective in inducing liver tumor necrosis as traditional PEI; its advantages are shorter treatment time and the capability of treating larger and multiple liver lesions.     

Transglutaminase in cell proliferation and transformation

Transglutaminase (TGase) activity was reduced in intact mitogen-stimulated human peripheral blood lymphocytes (PBL) when compared to intact resting PBL. Moreover, a treatment of the same quiescent immunocompetent cells with purified liver TGase and Ca²⁺ completely suppressed the mitogen-induced blast transformation. A decrease in TGase activity in neoplastically transformed seminal vesicle epithelial cells with respect to their normal parent counterpart was also observed. Our data support the notion of a possible implication of TGase in cell proliferation and transformation.     

Assessment of the scatter fraction evaluation methodology using Monte Carlo simulation techniques

To evaluate scatter fraction and scatter pair spatial distribution, experimental methods are generally used. These methods make use of a line source, placed along the FOV axis, inserted in a cylindrical phantom filled with air or water. The accuracy of these experimental methodologies can be tested by the use of a Monte Carlo method. In fact, the simulation allows the shape of the scatter event projection and the scatter fraction to be defined. An example of this application is the simulation package PETSI (PET SImulation). In this paper the comparison between the predicted scatter fraction and the experimentally evaluated one, obtained using an ECAT III PT 911/02 double ring whole body scanner are presented. PETSI permits additional data to be obtained: a) the true and scatter component of the energy spectrum; b) the spatial distribution, in the FOV plane, of the detected scatter events at different energy thresholds; c) the scatter to total detected events ratio; d) the predicted scatter fraction at both energy thresholds and FOV diameters. This information is very useful for optimizing both energy threshold and FOV size and to improve the accuracy of the currently used methods for the scatter fraction evaluation. Preliminary results of the predicted scatter fraction in a uniform phantom are presented.This article was presented at the 1st EEC workshop on accuracy determination in PET, January 19–20th. 1989 Pisa, Italy (COMAC-BME Concerted Project Characterization and Standardization of PET Instrumentation)     

Breast cancer micrometastases: Different interactions of carcinoma cells with normal and cancer patients' bone marrow stromata

The apparently dormant breast cancer micrometastases in haemopoietic marrow are correlated with distant metastatic carcinoma dissemination. We studied in vitro interactions of carcinoma cells with adjacent stromata, using connective tissue cell cultures from breast and bone marrow samples of normal donors, comparing them to the pericancerous breast tissue and bone marrows of 12 selected patients with invasive breast carcinomas. Cancer cells were detected by immunocytochemistry and RT-PCR in all the bone marrows and in most blood samples of the studied patients. We monitored the growth and interaction of carcinoma MCF-7 cells with the stromata. The normal breast stroma sustained typical massive cancer growth. The pericancerous breast stroma induced the invasive mesenchymal pattern of growth. Normal bone marrow stroma induced the same conversion and was highly adhesive, retaining the cells in the stroma, but carcinoma patients' bone marrow stromata underwent low adhesive interactions with cancer cells, releasing them potentially into the circulation. The semi-quantitative RT-PCR indicated an enhanced expression of the hepatocyte growth factor and its receptor c-met in breast and bone marrow stromata of cancer patients. The input of cancer cells into the normal bone marrow may induce modifications of the local microenvironment, favourable for growth and release of carcinoma cells into the systemic circulation, which correlate with the poor prognosis of patients with bone marrow micrometastases. This revised version was published online in July 2006 with corrections to the Cover Date.     

The role of nitrinergic connections in central cardiovascular responses mediated by physostigmine infused into posterior hypothalamus

In the last few decades, cholinergic connections located into posterior hypothalamus (PH) have been implicated in the central regulation of blood pressure (BP). Here we investigated the role of nitric oxide (NO) in the blood pressure response elicited by infusion of physostigmine into PH of normotensive rats. In freely moving rats, physostigmine (60-200 nM) produced a dose- and time-dependent elevation of BP which was antagonized by the antimuscarinic drug scopolamine (60 nM) and by L-NAME (100 microM), an inhibitor of NO synthase, both infused into the same site. In contrast, L-arginine (L-Arg; 100 microM), the precursor of NO, and glyceryltrinitrate (GTN; 140 nM), an NO donor, infused into the PH did not affect physostigmine-related pressor response. In rats pre-treated with Escherichia coli lipopolisaccharide (LPS; 0.5 microg i.p. 24h beforehand), however, scopolamine, L-Arg and GTN produced a decrease of BP, an effect antagonized by L-NAME. This suggests that NO only slightly modulates physostigmine-related pressor response elicited into PH of LPS-untreated rats. In contrast, the release of large amounts of NO generated by pre-treating rats with LPS, down-regulates cholinergic connections located at the PH, thus contributing in the central dysregulation of BP which can be found when high circulating endotoxin levels may occur.     

Effects of soy isoflavones on endothelial function in healthy postmenopausal women

OBJECTIVE: To evaluate the effects of soy isoflavone administration on endothelial function in healthy postmenopausal women. DESIGN: Sixty naturally postmenopausal women were randomly assigned to receive isoflavone or placebo tablets for 6 months. Endothelium-dependent vasodilatation was measured by brachial reactivity technique along with levels of plasma soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, P-selectin and soluble thrombomodulin, von Willebrand factor, and tissue plasminogen activator. Differences between endothelium-dependent and endothelium-independent vasodilatation were assessed by evaluating brachial reactivity parameters after reactive hyperemia and after sublingual administration of nitroglycerin; furthermore, in the active group, the effect of isoflavones was also evaluated during the intra-arterial infusion of N-monomethyl-L-arginine. Serum levels of lipids [high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides and lipoprotein(a)] and hemostatic factors (prothrombin, fibrinogen, plasminogen activator inhibitor-1, and fibrin D-dimer) were also measured. To confirm the absorption of isoflavones, their blood concentrations were determined. RESULTS: Isoflavone treatment versus placebo was associated with a significant improvement in endothelium-dependent vasodilatation but had no impact on endothelial-independent arterial diameter and flow. Intra-arterial infusion of N-monomethyl-L-arginine inhibited the significant effect of isoflavones on endothelium-mediated vasodilatation. Furthermore, isoflavone group experienced statistically significant reductions in plasma concentrations of ICAM-1, VCAM-1, and E-selectin. Levels of soluble thrombomodulin, von Willebrand factor, tissue plasminogen activator, lipids, and hemostatic factors did not change significantly throughout the study in both groups. CONCLUSIONS: Our findings suggest a positive influence of soy isoflavones on endothelial function in healthy postmenopausal women as evidenced by an improvement in endothelium-dependent vasodilatation and a reduction in plasma adhesion molecule levels.     

Identification of sixty-two novel and twelve known FBN1 mutations in eighty-one unrelated probands with Marfan syndrome and other fibrillinopathies

Marfan Syndrome (MFS) is an autosomal dominant disorder of the connective tissue due to mutations of Fibrillin-1 gene (FBN1) in more than 90% of cases and Transforming Growth Factor-Beta-Receptor2 gene (TGFB2R) in a minority of cases. Genotyping is relevant for diagnosis and genotype-phenotype correlations. We describe the FBN1 genotypes and related phenotypes of 81 patients who were referred to our attention for MFS or Marfan-like phenotypes. Patients underwent multidisciplinary pertinent evaluation in the adult or paediatric setting, according to their age. The diagnosis relied on Ghent criteria. To optimise DHPLC analysis of the FBN1 gene, all coding regions of the gene were directly sequenced in 19 cases and 10 controls: heterozygous amplicons were used as true positives. DHPLC sensitivity was 100%. Then, DHPLC was used to screen 62 other cases. We identified 74 FBN1 mutations in 81 patients: 64 were novel and 17 known. Of the 81 mutations, 41 were missense (50.6%), 27, either nonsense or frameshift mutations and predicted a premature termination codon (PTC) (33%), 11 affected splice sites (13.6%), and two predicted in-frame deletions (2.5%). Most mutations (67.9%) occurred in cbEGF-like modules. Genotype was clinically relevant for early diagnosis and conclusion of the diagnostic work-up in patients with incomplete or atypical phenotypes.     

Clinical and cost-effectiveness of a new nurse-led continence service: a randomised controlled trial

BACKGROUND: Continence services in the UK have developed at different rates within differing care models, resulting in scattered and inconsistent services. Consequently, questions remain about the most cost-effective method of delivering these services. AIM: To evaluate the impact of a new service led by a continence nurse practitioner compared with existing primary/secondary care provision for people with urinary incontinence and storage symptoms. DESIGN OF STUDY: Randomised controlled trial with a 3- and 6-month follow-up in men and women (n = 3746) aged 40 years and over living in private households (intervention [n = 2958]; control [n = 788]). SETTING: Leicestershire and Rutland, UK. METHOD: The continence nurse practitioner intervention comprised a continence service provided by specially trained nurses delivering evidence-based interventions using predetermined care pathways. They delivered an 8-week primary intervention package that included advice on diet and fluids; bladder training; pelvic floor awareness and lifestyle advice. The standard care arm comprised access to existing primary care including GP and continence advisory services in the area. Outcome measures were recorded at 3 and 6 months post-randomisation. RESULTS: The percentage of individuals who improved (with at least one symptom alleviated) at 3 months was 59% in the intervention group compared with 48% in the standard care group (difference of 11%, 95% CI = 7 to 16; P<0.001) The percentage of people reporting no symptoms or 'cured' was 25% in the intervention group and 15% in the standard care group (difference of 10%, 95% CI = 6 to 13, P = 0.001). At 6 months the difference was maintained. There was a significant difference in impact scores between the two groups at 3 and 6 months. CONCLUSIONS: The continence nurse practitioner-led intervention reduced the symptoms of incontinence, frequency, urgency and nocturia at 3 and 6 months; impact was reduced; and satisfaction with the new service was high.