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- Intravenous and intra-arterial digital subtraction angiography (DSA) was performed in 88 patients: 34 with tumours, 10 with renal trauma, 26 with suspected renovascular hypertension, 6 with vascular impression on the renal pelvis, 8 with nephrolithiasis and 4 with sonographically abnormal kidneys. Venous and arterial DSA always gave diagnostically useful images. Intravenous DSA is valuable in patients with suspected renovascular hypertension or after vascular surgery, percutaneous transluminal angioplasty and transcatheter embolisation. Arterial DSA is preferable to venous DSA in other clinical situations, particularly in the evaluation of renal tumours, and may be recommended in preference to conventional angiography. [ABSTRACT FROM AUTHOR]

Between 1983 and 1989, 15 patients with acute rupture of the thoracic aorta by blunt trauma were seen. Superior mediastinal widening and obscuration of the aortic arch were the most important findings on chest radiograph. Computed tomography examinations in 7 patients showed mediastinal hematomas but did not reveal aortic lesions. Definitive diagnosis of traumatic aortic rupture was established by aortography in all 15 patients. Intraarterial digital subtraction angiography proved to be as accurate as conventional film aortography and saved time. [ABSTRACT FROM AUTHOR]

Mutated KRAS serves as the oncogenic driver in 30% of non-small cell lung cancers (NSCLCs) and is associated with metastatic and therapy-resistant tumors. Focal Adhesion Kinase (FAK) acts as a mediator in sustaining KRAS-driven lung tumors, and although FAK inhibitors are currently undergoing clinical development, clinical data indicated that their efficacy in producing long-term anti-tumor responses is limited. Here we revealed two FAK interactors, extracellular-signal-regulated kinase 5 (ERK5) and cyclin-dependent kinase 5 (CDK5), as key players underlying FAK-mediated maintenance of KRAS mutant NSCLC. Inhibition of ERK5 and CDK5 synergistically suppressed FAK function, decreased proliferation and induced apoptosis owing to exacerbated ROS-induced DNA damage. Accordingly, concomitant pharmacological inhibition of ERK5 and CDK5 in a mouse model of Kras G12D -driven lung adenocarcinoma suppressed tumor progression and promoted cancer cell death. Cancer cells resistant to FAK inhibitors showed enhanced ERK5-FAK signaling dampening DNA damage. Notably, ERK5 inhibition prevented the development of resistance to FAK inhibitors, significantly enhancing the efficacy of anti-tumor responses. Therefore, we propose ERK5 inhibition as a potential co-targeting strategy to counteract FAK inhibitor resistance in NSCLC., (© 2024. The Author(s).)

Various lines of investigation support a signaling interphase shared by receptor tyrosine kinases and the DNA damage response. However, the underlying network nodes and their contribution to the maintenance of DNA integrity remain unknown. We explored MET-related metabolic pathways in which interruption compromises proper resolution of DNA damage. Discovery metabolomics combined with transcriptomics identified changes in pathways relevant to DNA repair following MET inhibition (METi). METi by tepotinib was associated with the formation of γH2AX foci and with significant alterations in major metabolic circuits such as glycolysis, gluconeogenesis, and purine, pyrimidine, amino acid, and lipid metabolism. 5'-Phosphoribosyl-N-formylglycinamide, a de novo purine synthesis pathway metabolite, was consistently decreased in in vitro and in vivo MET-dependent models, and METi-related depletion of dNTPs was observed. METi instigated the downregulation of critical purine synthesis enzymes including phosphoribosylglycinamide formyltransferase, which catalyzes 5'-phosphoribosyl-N-formylglycinamide synthesis. Genes encoding these enzymes are regulated through E2F1, whose levels decrease upon METi in MET-driven cells and xenografts. Transient E2F1 overexpression prevented dNTP depletion and the concomitant METi-associated DNA damage in MET-driven cells. We conclude that DNA damage following METi results from dNTP reduction via downregulation of E2F1 and a consequent decline of de novo purine synthesis., Significance: Maintenance of genome stability prevents disease and affiliates with growth factor receptor tyrosine kinases. We identified de novo purine synthesis as a pathway in which key enzymatic players are regulated through MET receptor and whose depletion via MET targeting explains MET inhibition-associated formation of DNA double-strand breaks. The mechanistic importance of MET inhibition-dependent E2F1 downregulation for interference with DNA integrity has translational implications for MET-targeting-based treatment of malignancies., (©2024 The Authors; Published by the American Association for Cancer Research.)

The DNA damage response (DDR) is intertwined with signaling pathways downstream of oncogenic receptor tyrosine kinases (RTKs). To drive research into the application of targeted therapies as radiosensitizers, a better understanding of this molecular crosstalk is necessary. We present here the characterization of a previously unreported MET RTK phosphosite, Serine 1016 (S1016) that represents a potential DDR-MET interface. MET S1016 phosphorylation increases in response to irradiation and is mainly targeted by DNA-dependent protein kinase (DNA-PK). Phosphoproteomics unveils an impact of the S1016A substitution on the overall long-term cell cycle regulation following DNA damage. Accordingly, the abrogation of this phosphosite strongly perturbs the phosphorylation of proteins involved in the cell cycle and formation of the mitotic spindle, enabling cells to bypass a G2 arrest upon irradiation and leading to the entry into mitosis despite compromised genome integrity. This results in the formation of abnormal mitotic spindles and a lower proliferation rate. Altogether, the current data uncover a novel signaling mechanism through which the DDR uses a growth factor receptor system for regulating and maintaining genome stability., (© 2023. The Author(s).)

Background: KRAS is the predominant oncogene mutated in pancreatic ductal adenocarcinoma (PDAC), the fourth cause of cancer-related deaths worldwide. Mutant KRAS-driven tumors are metabolically programmed to support their growth and survival, which can be used to identify metabolic vulnerabilities. In the present study, we aimed to understand the role of extracellularly derived fatty acids in KRAS-driven pancreatic cancer., Methods: To assess the dependence of PDAC cells on extracellular fatty acids we employed delipidated serum or RNAi-mediated suppression of ACSL3 (to inhibit the activation and cellular retention of extracellular fatty acids) followed by cell proliferation assays, qPCR, apoptosis assays, immunoblots and fluorescence microscopy experiments. To assess autophagy in vivo, we employed the Kras G12D/+ ;p53 flox/flox ;Pdx1-Cre ERT2 (KPC) mice crossed with Acsl3 knockout mice, and to assess the efficacy of the combination therapy of ACSL3 and autophagy inhibition we used xenografted human cancer cell-derived tumors in immunocompromised mice., Results: Here we show that depletion of extracellularly derived lipids either by serum lipid restriction or suppression of ACSL3, triggers autophagy, a process that protects PDAC cells from the reduction of bioenergetic intermediates. Combined extracellular lipid deprivation and autophagy inhibition exhibits anti-proliferative and pro-apoptotic effects against PDAC cell lines in vitro and promotes suppression of xenografted human pancreatic cancer cell-derived tumors in mice. Therefore, we propose lipid deprivation and autophagy blockade as a potential co-targeting strategy for PDAC treatment., Conclusions: Our work unravels a central role of extracellular lipid supply in ensuring fatty acid provision in cancer cells, unmasking a previously unappreciated metabolic vulnerability of PDAC cells., (© 2022. The Author(s).)

Mutant KRAS modulates the metabolic plasticity of cancer cells to confer a growth advantage during hypoxia, but the molecular underpinnings are largely unknown. Using a lipidomic screen, we found that PLCγ1 is suppressed during hypoxia in KRAS-mutant human lung adenocarcinoma cancer cell lines. Suppression of PLCγ1 in hypoxia promotes a less oxidative cancer cell metabolism state, reduces the formation of mitochondrial reactive oxygen species and switches tumour bioenergetics towards glycolysis by impairing Ca 2+ entry into the mitochondria. This event prevents lipid peroxidation, antagonizes apoptosis and increases cancer cell proliferation. Accordingly, loss of function of Plcg1 in a mouse model of Kras G12D -driven lung adenocarcinoma increased the expression of glycolytic genes, boosted tumour growth and reduced survival. In patients with KRAS-mutant lung adenocarcinomas, low PLCγ1 expression correlates with increased expression of hypoxia markers and predicts poor patient survival. Thus, our work reveals a mechanism of cancer cell adaptation to hypoxia with potential therapeutic value.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by marked fibrosis and low immunogenicity, features that are linked to treatment resistance and poor clinical outcomes. Therefore, understanding how PDAC regulates the desmoplastic and immune stromal components is of great clinical importance. We found that acyl-CoA synthetase long-chain 3 (ACSL3) is up-regulated in PDAC and correlates with increased fibrosis. Our in vivo results show that Acsl3 knockout hinders PDAC progression, markedly reduces tumor fibrosis and tumor-infiltrating immunosuppressive cells, and increases cytotoxic T cell infiltration. This effect is, at least in part, due to decreased plasminogen activator inhibitor-1 (PAI-1) secretion from tumor cells. Accordingly, PAI-1 expression in PDAC positively correlates with markers of fibrosis and immunosuppression and predicts poor patient survival. We found that PAI-1 pharmacological inhibition strongly enhances chemo- and immunotherapeutic response against PDAC, increasing survival of mice. Thus, our results unveil ACSL3-PAI-1 signaling as a requirement for PDAC progression with druggable attributes., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)

Mitochondria physically associate with the endoplasmic reticulum to coordinate interorganelle calcium transfer and regulate fundamental cellular processes, including inflammation. Deregulated endoplasmic reticulum-mitochondria cross-talk can occur in cystic fibrosis, contributing to hyperinflammation and disease progression. We demonstrate that Pseudomonas aeruginosa infection increases endoplasmic reticulum-mitochondria associations in cystic fibrosis bronchial cells by stabilizing VAPB-PTPIP51 (vesicle-associated membrane protein-associated protein B-protein tyrosine phosphatase interacting protein 51) tethers, affecting autophagy. Impaired autophagy induced mitochondrial unfolding protein response and NLRP3 inflammasome activation, contributing to hyperinflammation. The mechanism by which VAPB-PTPIP51 tethers regulate autophagy in cystic fibrosis involves calcium transfer via mitochondrial calcium uniporter. Mitochondrial calcium uniporter inhibition rectified autophagy and alleviated the inflammatory response in vitro and in vivo, resulting in a valid therapeutic strategy for cystic fibrosis pulmonary disease., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Enhanced prostaglandin production promotes the development and progression of cancer. Prostaglandins are generated from arachidonic acid (AA) by the action of cyclooxygenase (COX) isoenzymes. However, how cancer cells are able to maintain an elevated supply of AA for prostaglandin production remains unclear. Here, by using lung cancer cell lines and clinically relevant Kras G12D -driven mouse models, we show that the long-chain acyl-CoA synthetase (ACSL3) channels AA into phosphatidylinositols to provide the lysophosphatidylinositol-acyltransferase 1 (LPIAT1) with a pool of AA to sustain high prostaglandin synthesis. LPIAT1 knockdown suppresses proliferation and anchorage-independent growth of lung cancer cell lines, and hinders in vivo tumorigenesis. In primary human lung tumors, the expression of LPIAT1 is elevated compared with healthy tissue, and predicts poor patient survival. This study uncovers the ACSL3-LPIAT1 axis as a requirement for the sustained prostaglandin synthesis in lung cancer with potential therapeutic value.

The aim of this study was to evaluate in morbid obesity clinical and metabolic effects related to weight loss on liver steatosis (LS), measured through chemical-shift magnetic resonance imaging (MRI) and liver enzymes. Forty obese subjects (8 M/32 W; BMI 42.8 ± 7.12 kg/m(2), mean ± SD) were evaluated for LS through ultrasound (US-LS), chemical-shift MRI (MRI-LS), liver enzymes [aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyltransferase (GGT), alkaline phosphatase (ALP)], anthropometric parameters [weight, BMI, waist circumference (WC)], lipids, insulin, insulin resistance (HOMA-IR), glycated hemoglobin (HbA1c), oral glucose tolerance test, and body composition [fat mass (FM) and fat-free mass (FFM) at bio-impedance analysis (BIA)]. Anthropometric measures, MRI-LS, BIA, and biochemical parameters were reevaluated 6 months later in 18 subjects undergoing restrictive bariatric approach, i.e., intragastric balloon (BIB, n = 13) or gastric banding (LAGB, n = 5), and in 13 subjects receiving hypocaloric diet. At baseline, US-LS correlates only with MRI-LS, and the latter correlates with ALT, AST, and GGT. After 6 months, subjects undergoing BIB or LAGB had significant changes of BMI, weight, WC, ALT, AST, GGT, ALP, HbA1c, insulin, HOMA-IR, FM, FFM, and MRI-LS. Diet-treated obese subjects had no significant change of any parameter under study; change of BMI, fat mass, and fat-free mass was significantly greater in LAGB/BIB subjects than in diet-treated subjects. Change of MRI-LS showed a significant correlation with changes in weight, BMI, WC, GGT, ALP, and basal MRI-LS. Significant weight loss after BIB or LAGB is associated with decrease in chemical-shift MRI-LS and with reduction in liver enzymes; chemical-shift MRI and liver enzymes allow monitoring of LS in follow-up studies.

Aim: To assess a relationship between longitudinal changes in liver fat content and biochemical parameters in obese children after 1-year nutritional intervention., Methods: Forty-six obese children, 21 males and 25 females, aged 6-14 years, underwent metabolic measurements, liver ultrasonography (US) and chemical-shift magnetic resonance imaging (MRI) examinations at baseline and after 1-year nutritional intervention. A child was defined obese if her/his body mass index (BMI) was above the age- and sex-adjusted BMI Cole's curve passing through the cut-off of 30 kg/m(2) at 18 years. BMI Z scores were calculated and adjusted for age and gender by using the Cole's LMS-method and Italian reference data. Biochemistry included serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Abdominal US and chemical-shift MRI were performed according to a randomized sequence. The same radiologist performed US by a GE Logiq 9 (General Electric Healthcare Medical Systems, Milwaukee, WI, United States) using a 3.5-MHz convex array transducer. Liver echogenicity was evaluated independently on videotape by 3 radiologists unaware of the child and MRI outcomes, and a consensus was established. Another experienced radiologist, unaware of the child and US data, performed the abdominal chemical-shift MRI with a 1-t system NT-Intera (Philips Medical Systems, Best, The Netherlands) and a phased-array coil. Liver fat fraction (FF) on MRI was judged elevated when greater than 9%. A FF > 18% was considered expressing more severe cases of fatty liver according to Fishbein. A nutritional-behavioral intervention was recommended to promote a normocaloric balanced diet and active lifestyle based on the Italian guidelines for treatment of childhood obesity., Results: Compared to baseline, at the end of intervention children showed lower intakes of energy (mean ± SD: 2549 ± 1238 Kcal vs 1770 ± 622 Kcal, P < 0.0001), total fat (90 ± 47 g vs 52 ± 23 g, P < 0.0001), carbohydrates (356 ± 174 g vs 241 ± 111 g, P = 0.001), and protein (99 ± 48 g vs 75 ± 23 g, P = 0.006) intakes. Prevalence of FF ≥ 9% declined from 34.8% to 8.7% (P < 0.01), with a mean reduction of 7.8% (95%CI: 5.0-10.6). At baseline, FF was associated with liver biochemical parameters (maximum P < 0.001). At the end of the intervention association was found with AST (P = 0.017). Change of FF was associated with change in AST (P = 0.027) and ALT (P = 0.024). Rate of increased liver echogenicity declined from 45.6% to 21.7% (P < 0.0001). Liver echogenicity was associated with ALT at baseline only (P < 0.001). An age- and sex- adjusted multiple regression analysis showed that FF change was independently associated with change in serum AST (adjusted regression coefficient 0.348, P = 0.048)., Conclusion: The results suggest that in obese children longitudinal changes in liver fat content based on MRI may be associated with change in serum transaminases suggesting novelty in monitoring nonalcoholic fatty liver disease.

Introduction: Dopamine (DA) plays a key role in different aspects of the male sexual response, including sexual motivation and arousal, penile erection, and ejaculation. The modalities of action of DA are however unclear, although the various DA receptors may differentially mediate the activity of DA in different aspects of the male sexual response., Aim: To clarify the role of DA D(3) receptors in the control of the male sexual response., Methods: The effects of a highly selective DA D(3) receptors antagonist (SB-277011; intraperitoneal) were tested in experimental paradigms exploring several aspects of the male sexual response in (i) anesthetized rats using 7-hydroxy-N,N-di-n-propylaminotetralin to induce ejaculation and (ii) conscious rats using sexual incentive motivation and mating tests., Main Outcome Measures: Physiological markers of erection and emission and expulsion phases of ejaculation were measured in anesthetized rats. Behavioral parameters of sexual incentive motivation and mating tests were quantified., Results: In anesthetized rats, we found that SB-277011 specifically and dose-dependently inhibited the expulsion phase of ejaculation without impairing either emission phase or erection, and this resulted in delayed ejaculation. Administration of SB-277011 had no effect on the spontaneous preference that males displayed for sexually receptive females as shown in sexual incentive motivation test. Delayed ejaculation was confirmed when male rats were administered with the highest dose of SB-277011 (10 mg/kg) in mating test, where males were free to copulate with estrous females. In addition, the refractory period following ejaculation was lengthened in rats treated with SB-277011., Conclusion: As a whole, the present data demonstrate the specific and primary role of D(3) receptors in the expulsion phase of ejaculation and provide preclinical evidence for the investigation of the therapeutic potential of D(3) antagonism for treating premature ejaculation.

Activated carbon filters play an important role in water filtration and purification from contaminants of different origin. Their limit consists in bacterial proliferation, which may occur only during prolonged periods of non-use and in their ability to remove radioactive contaminants present in waste water from Industry or Nuclear Medicine departments. In this work we tested a commercially available activated carbon filter for water purification enriched with silver plated parts incubating in static condition at room temperature different micro organisms (Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Salmonella enteritidis, Staphylococcus aureus, Aspergillum niger), up to 78 days. The microbial growth was in general more inhibited in the presence of metal silver into the activated carbon in respect to filters with the activated carbon alone: >4log inhibition of bacterial proliferation after 78 days of incubation the presence of silver vs. 2log without silver. When the filters were incubated empty of carbon, the sterilizing power of silver was confirmed further. The activated carbon filters proved also their ability in removing from water the principal radioisotopes used for residues liquid medical and research purposes ((131)I, (99m)Tc, (201)Tl, (67)Ga). These results contribute useful data for the use of the silver-enriched carbon filters in water filtration both for daily use at home, and professional use in a Nuclear Medicine laboratory., (Copyright © 2008 Elsevier B.V. All rights reserved.)

Stressful life events are able to induce long-term modifications in physiological and neuroendocrine parameters that are related to the onset of several psychiatric disorders. To gain information on molecular modifications involved in long-term changes triggered by stress, we evaluated gene expression in the hippocampus of rats exposed to a single social defeat session. In the social defeat model, the experimental animal is defeated by a dominant male. The defeat induced an increase in body temperature, in distress vocalisations, in serum corticosterone levels and in anxiety-related behaviour measured with an open field test applied 6 h after the exposure to the dominant rat. In the open field test, anxiety-related behaviours were not detectable anymore 30 h after the exposure to the dominant rat and mRNA levels were evaluated at this time-point. The mRNA levels of genes modulated by stress (corticotropin-releasing factor; corticotropin-releasing factor receptor 1; corticotropin-releasing factor binding protein; mineralocorticoid and glucocorticoid receptors; Ca2+/calmodulin-dependent protein kinase-like kinase; Krox20; Bcl-2) and control genes (glyceraldehyde-3-phosphate dehydrogenase; beta-actin and cyclophilin A) were measured with real-time reverse transcription polymerase chain reaction. Corticotropin-releasing factor and glucocorticoid receptor mRNA levels were significantly modulated by the stress procedure, both genes showing an increase in rats exposed to a social defeat. No expression level differences were detected for the other genes. In conclusion, we report that 30 h after an acute social stress, a modification in mRNA levels can be detected in rat hippocampus, thus suggesting potential candidate genes involved in mediating long-term responses.

Purpose: To determine the usefulness of abdominal sonography in inherited diseases of carbohydrate metabolism., Materials and Methods: Thirty patients (age range, 4 months to 27 years) with glycogen storage diseases, galactosemia, disorders of fructose metabolism were studied with sonography. Echogenicity of the liver, sonographic dimensions of liver, kidneys and spleen were evaluated. Plasma blood parameters (ALT, AST, total cholesterol, triglycerides) were determined., Results: Liver was enlarged in 21/22 patients (95.4%) with glycogen storage diseases, in both subjects with disorders of fructose metabolism, and in 2/6 patients (33.3%) with galactosemia. Hepatic echogenicity was increased in 20/22 patients (90.9%) with glycogen storage diseases, and in the subject with hereditary fructose intolerance. Patients with galactosemia did not show increased liver echogenicity. Both kidneys were enlarged in 8/17 patients (47.0%) with glycogen storage disease type I. Subjects with increased hepatic echogenicity exhibited higher plasma concentrations of any blood parameter than the others with normal echogenicity (p<0.05)., Conclusions: Sonography can be useful in identification of inherited diseases of carbohydrate metabolism even if further examinations are necessary for an ultimate diagnosis.

Aims: The reversibility of extraskeletal calcifications in dialysis patients is an important and unresolved issue. Although periarticular calcifications have been shown to be reversible, little data are available on vascular or parenchymal calcifications., Case History: A patient on maintenance hemodialysis with severe hyperparathyroidism, hypercalcemia and hyperphosphatemia was admitted to undergo parathyroidectomy. A preoperative total body bone scintigraphy was performed to better evaluate a lytic lesion in the pelvis, the histology of which proved to be a "brown tumor". The scan showed the typical findings of renal osteodystrophy, but also a diffuse extra-skeletal uptake of bone tracer in the lungs, kidneys, femoral arteries and myocardium. After surgery, good control of serum calcium, phosphate (Ca x P product < 50 mg2/dl2) and PTH levels was maintained during 4 years of follow-up. Bone scans were repeated after 2 and 4 years, showing marked improvement of periarticular uptake at the ends of long bones. Extraosseous calcium deposition was still markedly evident, but progressively decreased (at 4 years: heart -36%, lungs -18%)., Conclusion: In this dialysis patient, extraskeletal calcification of visceral organs (particularly in the heart and the lungs) due to prolonged hypercalcemia and hyperphosphatemia was partially reversible by parathyroidectomy followed by good long-term control of serum phosphate and calcium.

This study investigated the effects of exposure to an intermittent homotypic stressor on: (i) habituation of acute autonomic responsivity (i.e. cardiac sympathovagal balance and susceptibility to arrhythmias), and (ii) circadian rhythmicity of heart rate, body temperature, and physical activity. After implantation of a transmitter for the radiotelemetric recording of electrocardiogram (ECG), body temperature and physical activity, adult male rats (Rattus norvegicus, Wild Type Groningen strain) were repeatedly exposed (10 consecutive times, on alternate days) to either a social stressor (defeat by a con-specific, n = 15) or an open-field, control challenge (transfer to a new cage; n = 8). ECGs, body temperature and physical activity were continuously recorded in baseline, test and recovery periods (each lasting 15 min), at the 1st and 10th episodes of both defeat and open-field challenge. The circadian rhythms of heart rate, body temperature and physical activity were monitored before (5 days), during (16 days) and after (21 days) the intermittent stress protocol. This study indicates that there is no clear habituation of either acute cardiac autonomic responsivity (as estimated by means of time-domain indexes of heart rate variability) or arrhythmia occurrence to a brief, intermittent, homotypic challenge, regardless of the nature of the stressor (social or non-social). On the other hand, rats exposed to social challenge also failed to show adaptation of acute temperature and activity stress responsiveness, whereas rats facing open-field challenge developed habituation of activity and sensitization of temperature responses. Repeated social challenge produced remarkable reductions of the heart rate circadian rhythm amplitude (this effect being significantly greater than that produced by intermittent open-field), but only minor changes in the daily rhythms of body temperature and physical activity.

Purpose: To measure the spleen length in patients with cirrhosis and portal hypertension with US and compare the measurements before and after orthotopic liver transplantation. To correlate splenic measures with laboratory data and Doppler flowmetry (mean portal vein flow velocity)., Materials and Methods: May, 1993, to January, 1997, fifteen patients with cirrhosis, portal hypertension and splenomegaly were examined and underwent orthotopic liver transplantation. The spleen length was measured before and after transplantation in 15/15 patients and it was also measured twice after transplantation in 10/15 patients. The mean portal venous flow velocity was measured before and after transplantation in 10/15 patients. The results were analyzed using the Student's t-test for paired and unpaired data; the association between the variables was evaluated by linear regression analysis; two-tailed p values were used., Results: At the first control after orthotopic liver transplantation (mean time from transplantation 5.5 +/- 2.6 months; range 2.5-12.5 months) a significant decrease was found in spleen length (179 +/- 32 to 149 +/- 30 mm, p = .0001; mean percent decrease = 16.7 +/- 9.9%), hypersplenism disappeared in 9/13 cases, mean portal venous flow velocity, measured in 10/15 patients, showed an increasing trend (16.0 +/- 9.0 to 22.3 +/- 9.0 cm/s). At the first control the correlation between the values of mean portal flow velocity measured before and after transplantation was not significant (r = .558, p = .0939); the same was true for the correlation between mean portal flow velocity and spleen length. The second measurement of the spleen length after transplantation (mean time from the first follow-up 18.1 +/- 7.8 months; range 6.4-32.8 months) in 10/15 subjects demonstrated no significant changes in the spleen dimensions relative to the first examination (139 +/- 24 mm to 138 +/- 26 mm), and in 1/10 case hypersplenism disappeared., Conclusions: The measurement of the spleen length is proposed for the follow-up of the patients with cirrhosis and hypersplenism before and after orthotopic liver transplantation. In our study, the mean decrease in spleen length was 17% in the period from transplantation to the first US examination. In the patients who underwent a second measurement after transplantation no significant change in spleen length was observed.