Ultrasonography in patients with chronic liver disease: its usefulness in the diagnosis of cirrhosis.

OBJECTIVE: To prospectively assess the usefulness of ultrasonography in predicting the presence of cirrhosis in patients with asymptomatic chronic liver disease in unknown stage. EXPERIMENTAL DESIGN: Eighteen doppler and ultrasonographic features were prospectively assessed immediately before performing laparoscopy and/or liver biopsy. Usefulness of predictive variables selected by multiple regression analysis and included in a scoring scale was determined by ROC curves. PATIENTS: One hundred and thirteen consecutive patients with neither clinical nor biochemical signs of advanced liver disease submitted for study. RESULTS: Liver enlargement, liver surface nodularity, liver parenchyma distortion, flattening of flow wave in hepatic veins, portal and splenic veins dilatation, decreased variability in splenic vein caliber with breathing. Collateral vessels, and splenomegaly were associated to cirrhosis. Multivariate analysis showed the joint assessment of hepatic echostructure, portal vein caliber and spleen area to be the best approach to ultrasonographic staging, with sensitivity of 80%, specificity of 92% and accuracy of 89% in the diagnosis of cirrhosis. CONCLUSIONS: Ultrasonography enabled the presence or absence of cirrhosis to be correctly determined even in patients with asymptomatic disease. Combined assessment of hepatic echostructure, portal vein diameter and spleen size provides the highest accuracy.     

Doppler ultrasonography in the assessment of renal hemodynamics in patients with chronic liver disease.

AIM: To assess renal hemodynamics by Doppler analysis of resistive index (RI) in small intrarenal arteries in patients with chronic liver diseases at different stages, and to analyze renal RI in patients with cirrhosis as a function of the absence or presence of ascites and the response to diuretic therapy. METHODS: Prospective cross-sectional study of 24 patients with chronic hepatitis, 39 with compensated cirrhosis, and 34 with ascites. The last group was divided into two subgroups: 1) responders to sodium restriction and a low dose of diuretics, and 2) patients with refractory ascites or those requiring high-dose therapy. RESULTS: Renal RI was increased in patients with cirrhosis and ascites (0.68 +/- 0.06) in comparison with patients with compensated cirrhosis (0.63 +/- 0.03, p < 0.01). Renal RI in the latter group was higher than in patients without cirrhosis (0.61 +/- 0.04, p < 0.05). Renal RI in patients with ascites was lower in subgroup 1 than in subgroup 2 (0.65 +/- 0.05 vs 0.72 +/- 0.06, p < 0.01). CONCLUSIONS: Renal RI increases as liver disease progresses. Patients with cirrhosis and ascites and increased RI require high-dose treatment or do not respond. Further studies are needed to demonstrate the predictive value of renal RI in assessing the effectiveness of diuretic therapy.     

Bronchiolitis obliterans in a patient previously working as a printer in a textile factory

We report the case of a 24-year-old man with a diagnosis of bronchiolitis obliterans, a rare clinical condition; the similarity to Ardystil syndrome was striking. Relevant occupational history included work in a textile air-brushing factory. Also noteworthy were lesions observed by CT scan in the form of cystic formations measuring less than 1 cm, a finding not previously described in the context of bronchiolitis obliterans. The patient improved immediately after starting corticoid treatment although scans failed to improve over several months of follow-up.     

Medium- and long-term survival after pacemaker implant: Improved survival with right ventricular outflow tract pacing

Introduction Long-term prognosis after pacemaker implant depends on numerous variables, particularly structural heart disease. There is evidence that apical stimulation could favor the development of heart failure and, therefore, influence mortality. Other right ventricular pacing sites have been studied, for example the outflow tract, but no reports regarding long-term clinical outcome are available. Objective Compare all-cause mortality between two different sites of stimulation in the right ventricle. Methods We retrospectively analyzed 150 consecutive patients who underwent pacemaker implantation because of complete AV block (spontaneous or after AV node ablation), symptomatic second-degree AV block, and symptomatic atrial fibrillation with slow ventricular response. All patients were implanted at the same institution with the standard technique. Apical stimulation was performed with a passive or active fixation lead and outflow tract pacing with an active fixation lead. Data collection period began in July 1999 and ended on December 2004. All patients included were greater than 70% ventricular paced during pacemaker follow-up. Patients older than 85 years were excluded from the analysis. Age, pacemaker mode, sex, ejection fraction, diabetes, and structural cardiac disease were analyzed. Mean age was 72 ± 7 years (median 74 years, range 27–85 years), 101 (67%) were male, 56 had implanted a VVI PM, and 94 patients a DDD PM. Patients were divided into two groups: outflow tract (55 patients) and apical pacing (95 patients). Mean follow-up was 1,231 ± 642 days (median 1,158 days, range 9 to 2,694 days), which ended on July 2007. Total mortality was examined with the Kaplan–Meier method to construct overall survival curves. Multivariate Cox proportional hazards regression models were performed. Results All patients or relatives were contacted personally or by phone. There were no major statistical differences in patient background between the two groups. During follow-up, 18 patients (32%) died in the outflow tract group and 49 (51%) in the apical group (log-rank p = 0.02). Cox regression multivariate analysis showed that outflow tract pacing and a low left ventricular ejection fraction (<40%) were the only independent variables with significant correlation with survival (p = 0.006 and 0.003, respectively). Conclusions Outflow tract pacing appears to improve medium- and long-term survival. Prospective randomized trials with a greater amount of patients are necessary to confirm the findings of this study.     

<Emphasis Type="Italic">Helicobacter pylori</Emphasis> Infection in Patients with Erosive Esophagitis Is Associated with Rapid Heartburn Relief and Lack of Relapse After Treatment with Pantoprazole

Previous studies have shown an increased effect of proton pump inhibitors on intragastric pH in Helicobacter pylori (HP)–infected patients suffering from gastroesophageal reflux disease (GERD). We evaluated the effect of HP infection on healing and symptom relief in GERD patients with erosive esophagitis treated with pantoprazole. Two hundred twenty-seven patients with endoscopically proven reflux esophagitis were treated for 8 weeks with pantoprazole, 40 mg daily. Patients achieving endoscopic healing at that time were treated for 16 weeks more with pantoprazole, 20 mg daily. Healing and symptom relief rates for HP infection were compared. We found complete relief of heartburn in 72.3% of the HP-positive versus 58.8% of the HP-negative group (P < 0.05). Overall prevalence of heartburn at 8 weeks was higher in the HP-negative group (40.3 vs. 25.8%; P < 0.05), with no significant differences in endoscopic healing (overall 80.4%). At 24 weeks of treatment, the symptomatic relapse rate was higher in the HP-negative group (25.9 vs. 10.2%; P < 0.020). At 8 weeks, patients with erosive esophagitis and HP infection exhibited a significantly better response to pantoprazole through complete heartburn relief, with no differences in endoscopic healing rates between the groups. After 24 weeks, the relapse rate was significantly higher in the HP-negative group.The Pantogerd Group is formed by S. Sanchiz, J. Sempere, J. A. Soto, J. J. Fernández, J. O. Gordillo, J. C. Porres, J. J. Allende, J. M. Zarate, J. Torrens, M. Alvarez, M. Fernández, M. Gene, R. Mancelle, M. A. Méndez, M. Villagrasa, P. López, F. De la Torre, M. García, P. Hergueta, G. Payeras, J. Barrio, D. Vicente, F. Vida, J. J. Sebastián, C. Madrona, F. J. Gallego, J. Ramírez, A. Machancoses, F. J. Martínez, M. L. Vignote, A. Poyatos, C. Jímenez, F. Gómez, F. Rubio, A. Linares, E. Cabrera, A. Sánchez.     

Low-dose irradiation promotes tissue revascularization through VEGF release from mast cells and MMP-9-mediated progenitor cell mobilization

Mast cells accumulate in tissues undergoing angiogenesis during tumor growth, wound healing, and tissue repair. Mast cells can secrete angiogenic factors such as vascular endothelial growth factor (VEGF). Ionizing irradiation has also been shown to have angiogenic potential in malignant and nonmalignant diseases. We observed that low-dose irradiation fosters mast cell-dependent vascular regeneration in a limb ischemia model. Irradiation promoted VEGF production by mast cells in a matrix metalloproteinase-9 (MMP-9)-dependent manner. Irradiation, through MMP-9 up-regulated by VEGF in stromal and endothelial cells, induced the release of Kit-ligand (KitL). Irradiation-induced VEGF promoted migration of mast cells from the bone marrow to the ischemic site. Irradiation-mediated release of KitL and VEGF was impaired in MMP-9-deficient mice, resulting in a reduced number of tissue mast cells and delayed vessel formation in the ischemic limb. Irradiation-induced vasculogenesis was abrogated in mice deficient in mast cells (steel mutant, Sl/Sl(d) mice) and in mice in which the VEGF pathway was blocked. Irradiation did not induce progenitor mobilization in Sl/Sl(d) mice. We conclude that increased recruitment and activation of mast cells following irradiation alters the ischemic microenvironment and promotes vascular regeneration in an ischemia model. These data show a novel mechanism of neovascularization and suggest that low-dose irradiation may be used for therapeutic angiogenesis to augment vasculogenesis in ischemic tissues.     

Postmenopausal Canarian women receiving oral glucocorticoids have an increased prevalence of vertebral fractures and low values of bone mineral density measured by quantitative computer tomography and dual X-ray absorptiometry, without significant changes in parathyroid hormone

BACKGROUND: Daily doses higher than 7.5 mg/daily of prednisone or equivalents confer a great risk of vertebral and hip fractures with a clear dose dependence of fracture risk. Information regarding the utility in assessing trabecular bone mineral density by quantitative computer tomography (QCT) in these patients, either in the Canaries or in Spain, is lacking. Moreover, in this setting, the importance of secondary hyperparathyroidism is still controversial. DESIGN, PATIENTS AND METHODS: Cross-sectional observational study performed on 1177 consecutive Canary postmenopausal women who attended our Bone Metabolic Unit. The Patient Group was composed of 88 postmenopausal women who were taking oral corticosteroids in dose higher than 7.5 mg/day of prednisone or equivalent for more than 6 months (OG group). The Control Group included 838 postmenopausal women who did not take steroids. A complete validated questionnaire for osteoporosis risk assessment and a complete physical examination were performed. A lateral X-ray of the spine was performed on every woman. Bone mineral density (BMD) was measured at the lumbar spine (LS) by dual X-ray Absorptiometry (DXA) and QCT and at the femoral neck by DXA. Fasting serum and 24 hour urine was collected and biochemical markers of bone remodelling were studied. RESULTS: Both groups were comparable in general characteristics and calcium intake. The OG group showed lower values of BMD estimated both by DXA and QCT (p<0.05). LS BMD was closely correlated by using both methods (r=0.636, p<0.001). The OG group showed lower values of osteocalcin (p=0.023) and TRAP (p=0.026) without significant differences in PTH. Patients in OG group had a higher prevalence of vertebral fractures than controls (13.3% vs 8.6%; crude values: p=0.049, OR: 1.63 (0.99-2.67); age adjusted: p=0.003, OR 2.29 (1.33-9.93)). CONCLUSIONS: In postmenopausal Canarian women, chronic glucocorticoid therapy is associated with low bone mineral density, measured either by DXA or QCT, with evidence of low turnover and high prevalence of fractures without significant changes in PTH. DXA and QCT provide similar information in the assessment of this high risk population.     

Acute pancreatitis mimicking acute inferior myocardial infarction

A 56-year-old man presented with acute pancreatitis and electrocardiographic abnormalities, suggesting acute inferior myocardial infarction. An emergent coronary angiogram showed normal coronary arteries. The clinical significance and therapeutic implications of this rare finding are discussed.     

Involvement of nitric oxide in the non-adrenergic non-cholinergic neurotransmission of horse deep penile arteries: role of charybdotoxin-sensitive K(+)-channels.

1. The involvement of nitric oxide (NO) and the signal transduction mechanisms mediating neurogenic relaxations were investigated in deep intracavernous penile arteries with an internal lumen diameter of 600-900 microns, isolated from the corpus cavernosum of young horses. 2. The presence of nitric oxide synthase (NOS)-positive nerves was examined in cross and longitudinal sections of isolated penile arteries processed for NADPH-diaphorase (NADPH-d) histochemistry. NADPH-d-positive nerve fibres were observed in the adventitia-media junction of deep penile arteries and in relation to the trabecular smooth muscle. 3. Electrical field stimulation (EFS) evoked frequency-dependent relaxations of both endothelium-intact and denuded arterial preparations treated with guanethidine (10(-5) M) and atropine (10(-7) M), and contracted with 10(-6) M phenylephrine. These EFS-induced relaxations were tetrodotoxin-sensitive indicating their non-adrenergic non-cholinergic (NANC) neurogenic origin. 4. EFS-evoked relaxations were abolished at the lowest frequency (0.5-2 Hz) and attenuated at higher frequencies (4-32 Hz) by the NOS inhibitor, NG-nitro-L-arginine (L-NOARG, 3 x 10(-3) M). This inhibitory effect was antagonized by the NO precursor, L-arginine (3 x 10(-3) M). NG-nitro-D-arginine (10(-4) M) did not affect the relaxations to EFS. 5. Incubation with either the NO scavenger, oxyhaemoglobin (10(-5) M), or methylene blue (10(-5) M), an inhibitor of guanylate cyclase activation by NO, caused significant inhibitions of the EFS-evoked relaxations, and while oxyhaemoglobin abolished the relaxations to exogenously added NO (acidified sodium nitrite, 10(-6) - 10(-3) M), there still persisted a relaxation to NO of 24.4 +/- 5.1% (n = 6) in the presence of methylene blue. 6. Glibenclamide (3 x 10(-6) M), an inhibitor of ATP-activated K(+)-channels, did not alter the relaxations to either EFS-stimulation or NO, while the blocker of Ca(2+)-activated K(+)-channels, charybdotoxin (3 x 10(-8) M), caused a significant inhibition of both the electrically-induced relaxations and the relaxations to exogenously added NO. Furthermore, charybdotoxin blocked relaxations induced by the cell permeable analogue of cyclic GMP, 8-bromo cyclic GMP (8 Br-cyclic GMP). 7. These results suggest that relaxations of horse deep penile arteries induced by NANC nerve stimulation involve mainly NO or a NO-like substance from nitrergic nerves. NO would stimulate the accumulation of cyclic GMP followed by increases in the open probability of Ca(2+)-activated K(+)-channels and hyperpolarization leading to relaxation of horse penile arteries.     

Irinotecan plus raltitrexed as first-line treatment in advanced colorectal cancer: a phase II study

To evaluate the efficacy and toxicity of irinotecan (CPT-11) in combination with raltitrexed as first-line treatment of advanced colorectal cancer (CRC). A total of 91 previously untreated patients with advanced CRC and measurable disease were enrolled in this phase II study. The median age was 62 years (range 31-77); male/female 54/37; ECOG performance status was 0 in 50 patients (55%), one in 39 (43%) and two in two (2%). Treatment consisted of CPT-11 350 mg x m(-2) in a 30-min intravenous infusion on day 1, followed after 30 min by a 15-min infusion of raltitrexed 3 mg x m(-2). Measurements of efficacy included the following: response rate, time to disease progression and overall survival. Of the 83 evaluable patients valuable to objective response, there were five complete responses (6%) and 23 partial responses (28%), for an overall response rate of 34% (95% CI: 25.9-46.5%). In all, 36 patients (43%) had stable disease, whereas 19 (23%) had a progression. The median time to progression was 11.1 months and the median overall survival was 15.6 months. A total of 487 cycles of chemotherapy were delivered with a median of five per patient. Grade 3-4 WHO toxicities were as follows: diarrhoea in 13 patients (15%), nausea/vomiting in four (4%), transaminase increase in six (7%), stomatitis in two (2%), febrile neutropenia in three (3%), anaemia in five (6%) and asthenia in three (3%). The combination CPT-11-raltitrexed is an effective, well-tolerated and convenient regimen as front-line treatment of advanced CRC.