Genetic analysis on growth and carcass traits in Nelore cattle.

In this study, the objective was to estimate genetic parameters of body weight at 210 (BW210) and 365 (BW365) days of age in relation to rib eye area (REA), subcutaneous back fat thickness (BF) and rump fat (RF), and their respective genetic trends, in Nelore beef cattle. Estimates of genetic parameters and breeding values for the studied traits were obtained using the REML method. The direct and maternal heritability estimates were respectively: 0.25±0.02 and 0.21±0.01, for BW210, and 0.29±0.02 and 0.09±0.01, for BW365. The heritability estimates for transformed REA, BF and RF were 0.29±0.03, 0.21±0.02 and 0.23±0.03, respectively. There were genetic associations between BW210 and REA, BW365 and REA, and BF and RF, while the other correlations were low. The selection process that was conducted at the farms participating in the breeding program, taking the proposed selection index into consideration, caused genetic changes to these traits.

Increased activation of p38 MAPK in COPD.

Inflammation, oxidative stress and apoptosis, which are involved in chronic obstructive pulmonary disease (COPD) pathogenesis, may activate the p38 subgroup of mitogen-activated protein kinases (MAPKs). Therefore, the aim of the present study was to evaluate the expression of the phosphorylated, active form of p38 MAPK (phospho-p38) in the lungs of COPD patients. Surgical specimens were obtained from 18 smokers with COPD at different stages of disease severity, plus nine smoking and eight nonsmoking subjects with normal lung function. Phospho-p38+ cells were quantified by immunohistochemistry in both alveolar spaces and alveolar walls. Moreover, a Western blot analysis of phospho-p38 and total p38alpha isoform expressed by alveolar macrophages was performed. Phospho-p38+ alveolar macrophages and phospho-p38+ cells in alveolar walls were increased in patients with severe and mild/moderate COPD, compared with smoking and nonsmoking controls. Moreover, they were inversely correlated to values of forced expiratory volume in one second (FEV(1)) and FEV(1)/forced vital capacity. Western blot analysis showed that phosphorylated p38, but not the total p38alpha isoform, was specifically increased in alveolar macrophages from COPD patients. Activation of the p38 mitogen-activated protein kinase pathway appears to be involved in the pathogenesis of chronic obstructive pulmonary disease. The present findings suggest that this protein may be a suitable pharmacological target for therapeutic intervention.

Out-patient high-dose-rate endobronchial brachytherapy for palliation of lung cancer: an observational study.

BACKGROUND AND AIM: Out-patient high-dose-rate endobronchial brachytherapy (HDREB) is a possible option in the palliation of symptoms in patients with advanced lung cancer, but literature data is limited and the technique is still under development in Italy. Our aim was to evaluate safety and effectiveness of out-patient HDREB for palliation of malignant endobronchial tumours in the context of a multidisciplinary approach. METHODS: Out-patient HDREB sessions were scheduled at weekly intervals (500-1000 cGy per session) with prior Diodi-laser resection in some cases. Response was assessed bronchoscopically, clinically and functionally at the end of treatment and one month after the last HDREB session. Inclusion criteria was: histological evidence of malignant tumour not susceptible to surgical treatment for extension or co-morbidity. RESULTS: 150 outpatient HDREB sessions were carried out on consecutive 35 patients (mean age 69 yrs, M/F 29/6) with symptoms due to central airway obstruction. A shortterm endoscopic response was observed in 15/28 patients. After delivering 2000 cGy dyspnoea decreased significantly. After one month cough decreased and haemoptysis disappeared. Palliation was obtained in all patients except one during. Lung function tests did not significantly improve after HDREB. No fatal complication occurred. A temporary radiation bronchitis was observed in six patients. CONCLUSIONS: This non-comparative, prospective observational study showed a palliative response of HDREB in most of patients with advanced endoluminal lung cancer. The safety of the procedure was good and the rate of non-fatal serious complications was very low.

Transforming growth factor-beta type II receptor in pulmonary arteries of patients with very severe COPD.

A mild-to-moderate increase in pulmonary arterial pressure is often associated with severe chronic obstructive pulmonary disease (COPD). Transforming growth factor (TGF)-beta is a cytokine involved in the maintenance of integrity of vasculature. The aim of the study was to investigate whether the TGF-beta pathway might be involved in the development of pulmonary hypertension associated with COPD. Surgical specimens from 14 patients undergoing lung transplantation for very severe COPD (forced expiratory volume in one second 17 +/- 2% of the predicted value) and from seven donors were examined. The expression of TGF-beta1 and TGF-beta type II receptor (TGF-betaRII), cell proliferation index and structural changes in pulmonary arteries were quantified immunohistochemically. In severe COPD patients, increased expression of TGF-betaRII was observed in both the tunica media and intima, which was associated with a normal proliferation index in both layers. Conversely, significant thickening of the tunica intima, which was not present in the tunica media, was observed, suggesting that mechanisms other than cell proliferation may be involved in intimal thickening. In conclusion, in the pulmonary arteries of patients with severe chronic obstructive pulmonary disease, there is upregulation of transforming growth factor-beta type II receptor expression associated with a normal proliferation index. These findings suggest the activation of an antiproliferative pathway, which might explain the relatively low degree of pulmonary hypertension observed in these subjects.

Upregulation of basic fibroblast growth factor in smokers with chronic bronchitis.

The aim of the study was to investigate the expression of basic fibroblast growth factor (bFGF) and its receptor, fibroblast growth factor receptor (FGFR)-1, in the central airways of smokers with chronic bronchitis. The lobar bronchi from 17 subjects undergoing thoracotomy for solitary nodules were examined. All had a history of cigarette smoking, nine had symptoms of chronic bronchitis and airflow limitation, and eight were asymptomatic with normal lung function. Using immunohistochemical methods, bFGF and FGFR-1 expression in the total airway wall and the different airway compartments, i.e. bronchial glands, submucosal vessels and smooth muscle, was quantified. Moreover, to investigate the role of bFGF in angiogenesis, the number of submucosal vessels was quantified. Smokers with chronic bronchitis had an increased bFGF expression in the total airway wall compared with asymptomatic smokers, which was mainly due to bFGF upregulation in bronchial glands. By contrast, the expression of FGFR-1 and the number of submucosal vessels was similar in the two groups of subjects examined. In conclusion, smokers with chronic bronchitis have an increased expression of basic fibroblast growth factor in the central airways, which is mainly due to an increased expression in bronchial glands, suggesting the involvement of this growth factor in the pathogenesis of chronic bronchitis.

Decreased expression of TGF-beta type II receptor in bronchial glands of smokers with COPD.

BACKGROUND: The role of transforming growth factor-beta1 (TGF-beta1) in chronic obstructive pulmonary disease is still controversial, but it has been proposed that it may protect from mucus hypersecretion since it is able to downregulate mucin production. A study was undertaken to investigate the expression of TGF-beta1 and its type II receptor (TGF-beta RII) in the bronchial glands of smokers with COPD. METHODS: The expression of TGF-beta(1) and TGF-beta RII were examined immunohistochemically in the bronchial glands of 24 smokers undergoing lung resection for solitary peripheral nodules: 12 with airflow limitation (smokers with COPD) and 12 with normal lung function. RESULTS: The expression of TGF-beta1 in bronchial glands was similar in the two groups of subjects while that of TGF-beta RII was lower in smokers with COPD than in smokers with normal lung function (p=0.004). TGF-beta RII expression was inversely correlated with the values of Reid's index, a measure of gland size (p=0.02, r=-0.50). CONCLUSIONS: In the bronchial glands of smokers with COPD there is decreased expression of TGF-beta RII which is associated with bronchial gland enlargement. These findings support the view that the absence of TGF-beta signalling may induce structural changes in the bronchial glands which, in turn, may promote mucus hypersecretion.

High-dose N-acetylcysteine in patients with exacerbations of chronic obstructive pulmonary disease.

OBJECTIVE: To investigate the efficacy and tolerability of high-dose N-acetylcysteine (NAC) in the treatment of patients with exacerbations of chronic obstructive pulmonary disease (COPD). DESIGN AND PATIENTS: Randomised, double-blind, double-dummy, placebo-controlled study in 123 patients experiencing an acute exacerbation of COPD. INTERVENTIONS: NAC 1200 mg/day, 600 mg/day or placebo administered once daily for 10 days. MAIN OUTCOME MEASURES: The primary objective was to assess the proportion of patients with normalised C-reactive protein (CRP) levels. Also assessed were effects on interleukin (IL)-8 levels, lung function and symptoms. RESULTS: Both NAC 600 and 1200 mg/day were associated with a significantly higher proportion of patients achieving normalised CRP levels compared with placebo (52% and 90% vs 19% of patients; p

Neutrophilic infiltration within the airway smooth muscle in patients with COPD.

BACKGROUND: COPD is an inflammatory disorder characterised by chronic airflow limitation, but the extent to which airway inflammation is related to functional abnormalities is still uncertain. The interaction between inflammatory cells and airway smooth muscle may have a crucial role. METHODS: To investigate the microlocalisation of inflammatory cells within the airway smooth muscle in COPD, surgical specimens obtained from 26 subjects undergoing thoracotomy (eight smokers with COPD, 10 smokers with normal lung function, and eight non-smoking controls) were examined. Immunohistochemical analysis was used to quantify the number of neutrophils, macrophages, mast cells, CD4+ and CD8+ cells localised within the smooth muscle of peripheral airways. RESULTS: Smokers with COPD had an increased number of neutrophils and CD8+ cells in the airway smooth muscle compared with non-smokers. Smokers with normal lung function also had a neutrophilic infiltration in the airway smooth muscle, but to a lesser extent. When all the subjects were analysed as one group, neutrophilic infiltration was inversely related to forced expiratory volume in 1 second (% predicted). CONCLUSIONS: Microlocalisation of neutrophils and CD8+ cells in the airway smooth muscle in smokers with COPD suggests a possible role for these cells in the pathogenesis of smoking induced airflow limitation.

Pathogenesis and pathology of COPD.

Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation. Since flow is the result of a driving pressure that promotes flow and of an opposing resistance that contradicts it, the reduction in flow observed in COPD has two main components: increased resistance, which is due to airway obstruction, and a loss of the elastic recoil pressure of the lung, which is due to parenchymal destruction. Although it has long been known that the major site of increased resistance in COPD is the peripheral airways, recent studies have shown that central airways are involved in the disease as well. The purpose of this review is to describe the major structural and cellular changes present in peripheral airways, central airways and lung parenchyma of patients with COPD, and to underline the possible mechanisms contributing to airflow limitation in these subjects.

Structural basis for airflow limitation in chronic obstructive pulmonary disease.

The airflow limitation that characterises chronic obstructive pulmonary disease (COPD) has two main components: an increased resistance, which is due to airway obstruction, and a loss of the elastic recoil pressure of the lung, which is due to parenchymal destruction. Although it has long been known that the major site of increased resistance in COPD is the peripheral airways, recent studies have shown that central airways are involved in the disease as well. The purpose of this review is to describe the major structural and cellular changes present in peripheral airways, central airways and lung parenchyma of patients with COPD, and to underline the possible mechanisms contributing to airflow limitation in these subjects.

Nomograms for the administration of unfractionated heparin in the initial treatment of acute thromboembolism--an overview.

Despite the availability of low-molecular-weight heparins, unfractionated heparin (UFH) still remains the drug of choice for the initial treatment of acute venous thromboembolism in many countries. When appropriately employed, UFH treatment results in a degree of efficacy and safety that is fully comparable with that obtained with the use of heparin derivatives. The use of nomograms for the intravenous or subcutaneous administration of UFH assures that virtually all patients will promptly achieve adequate levels of anticoagulation, thus decreasing the likelihood of recurrent venous thromboembolism without extra bleeding-risk. In this article we reviewed clinical studies on the implementation and validation of UFH dosing nomograms, and attempted a quantitative analysis of their performance. According to the results of our analysis, a statistically significantly higher proportion of patients treated on the basis of a nomogram reached a therapeutic anticoagulant level within 24 h of treatment, as compared to patients treated following the standard practice (odds ratio, 3.6; 95% CI, 2.6 to 4.9). The rate of recurrent thromboembolic events was significantly lower for patients treated according to a nomogram (odds ratio, 0.3; 95% CI, 0.1 to 0.8), while no significant differences in terms of either major or minor bleedings were detected between nomogram patients and controls.

A randomized trial of cefepime and ceftazidime for the treatment of community-acquired pneumonia.

We compared the effectiveness and safety of ceftazidime and cefepime in hospitalized patients with community-acquired pneumonia. The 148 enrolled patients received 2 g ceftazidime three times daily or 2 g cefepime twice daily. The clinical success rate was the same for both drugs. Even the microbiological effectiveness was similar. Both drug regimens were well tolerated. We conclude that 2 g ceftazidime three times daily were as effective as 2 g cefepime twice daily for the treatment of community-acquired pneumonia in hospitalized patients. The cost of ceftazidime treatment was, however, higher than the cost of cefepime treatment.

Subjects with obstructive pulmonary disease tend to be chronically vasodilated.

1. In 12 unselected outpatients with chronic obstructive pulmonary disease and six controls, arterial pH, PaO2, PaCO2 and oxygen saturation (SaO2), forced expiratory volume in 1.0 s (FEV1.0) and vital capacity were measured. Subjects were grouped into those with or without obstruction based on the Tiffenau index. The Baseline Dyspnoea Index was employed to objectify the severity of dyspnoea and the Borg index to evaluate the subjective sensation. Blood pressure was measured with a sphygmomanometer; calf arterial flow both at rest and during reactive hyperaemia with a plethysmograph. Basal and minimal resistance were calculated.2.FEV1.0 was 26% lower in patients with obstruction than in controls, and was also lower in patients with moderate-to-severe obstruction compared with those with mild or no obstruction. Arterial flow (75% greater in the patients with obstruction) progressively increased with increasing severity of obstruction, being 54% higher in those with mild obstruction than in those with no obstruction (P<0.001), and 28% higher in moderate-severe than in mild obstruction (P<0.005). In multiple regressions, F correlated inversely with FEV1.0, PaO2 and SaO2, and directly with PaCO2. Basal resistance correlated positively with FEV1.0, SaO2 and the Tiffenau index, and inversely with PaCO2 (r=-0.52, P=0.02). Minimal resistance was significantly lower in obstructed than in non-obstructed subjects. Both basal and minimal resistance progressively decreased, although insignificantly, with worsening bronchial obstruction. PaCO2 did not correlate with any haemodynamic parameter. Borg index correlated indirectly with FEV1.0 and basal resistance directly with arterial flow.3. Patients with chronic obstructive pulmonary disease therefore tend to show chronic vasodilatation depending on hypoxia rather than PaCO2. Other mechanisms could be involved in this phenomenon. The Borg index is a good indicator of oxygen desaturation and vasodilatation.

Pre-operative chemoradiotherapy in non-small cell lung cancer stage III patients. Feasibility, toxicity and long-term results of a phase II study.

The aim of this study was to evaluate the feasibility, the response rate and the effect on survival of full dose polychemotherapy delivered concurrently with bifractionated radiotherapy at a radical dose, in a subset of patients with marginally resectable or unresectable stage IIIA-B non-small cell lung cancer (NSCLC). Treatment consisted of two courses of cisplatin 100 mg/m2 for 1 day plus etoposide 120 mg/m2 for 3 days delivered from day 1 to day 22, plus radiotherapy delivered in two cycles of 2560 cGy each from day 3 to day 12 and from day 24 to 33 (total dose 5120 cGy in 31 days). The daily dose was 320 cGy in two equal fractions. After surgery, three additional courses of cisplatin plus etoposide were planned. From February 1988 to June 1991, 39 patients with stage III NSCLC (19 were judged as having marginally resectable, 20 as having unresectable disease) were entered into the study. Out of 39 patients (22 squamous cell carcinoma, 17 adeno/large cell carcinoma), 24 had stage IIIa (62%) and 15 stage IIIb (38%). Median PS was 80 (70-90). A total of 78 (74 evaluable) concurrent cycles of pre-operative chemoradiotherapy were delivered. The prominent side-effect was leucopenia: leucopenia > or = grade 3 at nadir occurred in 20 cycles (27%), thrombocytopenia > or = grade 3 at nadir in seven cycles (9%), 19 patients (54%) had a treatment delay of 1 week between the two cycles. Other important toxicities were sepsis in 5 patients (13%), oesophagitis > grade 2 in 9 patients (23%) and pneumonitis in 5 patients (13%). The response rate was 67% (6 CR (complete response), 16%; 19 PR (partial response), 51%). A resection was subsequently performed in 20 (51%) patients: 14 out of 19 marginally resectable (74%) and 6 out 20 initially unresectable (30%) patients. One other patient had an exploratory thoracotomy. Surgical specimens were tumour-free in 3 patients (14%); in 8 patients (38%) only microscopic tumour was found, and in 10 (48%) macroscopic residual tumour was found. Out of 23 patients attaining a CR, 5 relapsed locally and 11 only distantly. At present, with a follow-up ranging from 64 to 90 months, 34 patients have died, 1 is alive with recurrent disease and 4 (17%) are alive without evidence of disease. Median survival was 16 months, with 18% 3-year survivors and 13% 5-year survivors. Resected patients had a median survival of 21 months, versus 10 months for unresected patients (P = 0.01). No significant difference was evident between stage IIIa and stage IIIb patients.

[Has the role of radiology changed in the fight against pulmonary tuberculosis?]. / E cambiato il ruolo della radiologia nella lotta alla tubercolosi polmonare?

Tuberculosis is on the increase in Italy as in other industrial countries. The key to tuberculosis control is case finding and radiology plays a major role in both active and passive tuberculosis diagnosis. Have recent advances in radiologic techniques increased the value of conventional radiology? Has the role of chest radiography changed in tuberculosis screening? To answer these questions we examined a population referred to our hospital for both screening and diagnostic purposes over a 12-month period. In a population of 31,730 inhabitants, 1,461 chest radiographs were performed, 226 (15.4%) for passive and the others for active case finding. As for active case finding, high-risk patients were screened (21 immigrants and 296 aging people), together with the general population believed to be at risk according to current national recommendations (918 chest films). While screening allowed the diagnosis of only one tuberculosis case in the high-risk group, 3 cases were found in the symptomatic group with the passive protocol. In our experience, new radiologic techniques have not made the diagnosis of tuberculosis easier. Unlike in cancers, CT was not particularly useful in identifying symptomatic tuberculosis cases. In our experience, screening yielded poor results: in fact, this attempt at preventing tuberculosis caused an unreasonable waste of time and money because when screening low-risk groups many films are needed to diagnose a single case. Thus, the reason for this failure was not a technical one. It proved to be a problem of selecting the population to be screened. Our results suggest that no major change has taken place in the role of conventional radiology in passive tuberculosis case finding and that radiology must be used differently in passive case finding, that is, for screening purposes in high-risk groups only.

Prognostic usefulness of hepatic vein catheterization in patients with cirrhosis and esophageal varices.

Clinical and anamnestic data, Pugh score, and size of esophageal varices were obtained in 129 cirrhotics. Hepatic vein catheterization was performed to measure hepatic venous pressure gradient (HVPG), indocyanine green (ICG) intrinsic hepatic clearance, and hepatic plasma flow. During a follow-up period of up to 60 months, 44 patients experienced gastrointestinal bleeding and 54 died. Applying Cox regression analysis, ICG intrinsic hepatic clearance, Pugh score, previous variceal bleeding, and HVPG were the only significant prognostic determinants of survival. In addition, Cox's regression analysis showed that HVPG, Pugh score, size of varices, and previous variceal bleeding all contained significant prognostic information regarding risk of gastrointestinal bleeding. The models were validated using a split-sample technique, and prognostic indexes for death and gastrointestinal bleeding were calculated. The prognostic index predicting death had significantly improved prognostic accuracy over a prognostic index calculated excluding the data obtained from hepatic vein catheterization (P less than 0.05). In conclusion, prognostic accuracy in cirrhosis with portal hypertension is significantly improved by information obtained from hepatic vein catheterization.

Evaluation of splanchnic angiography as a prognostic index of survival in patients with cirrhosis.

Prognostic evaluation of advanced liver disease is usually made on the basis of the common clinical and biochemical data included in the Child-Turcotte classification. The aim of this study was to evaluate the contribution of data from splanchnic angiography as a guide to prognosis in patients with cirrhosis. Over an 8-year period 219 patients with cirrhosis were investigated by splanchnic angiography and followed up prospectively. At the end of the study 95 patients had died (43.4%). Median survival time was 68 months. In addition to several clinical and biochemical data, hepatic portal venous perfusion and the presence of caudad hepatofugal veins as assessed by angiography were significant predictors of survival. Incorporating all nonangiographic variables in a Cox's multiple regression analysis, a clinicobiochemical set of prognostic covariates (ascites, s-albumin, gammaglobulins, s-alkaline phosphatase, and sex) was selected. When adding to this model each of the angiographic variables, only portal perfusion resulted in an independent predictor of survival. In conclusion, in cirrhotics the angiographic evaluation of portal perfusion improved the prognostic information obtained from clinical and biochemical data.

[Methacholine test in the study of non-specific bronchial reactivity in a group of patients allergic to pollen]. / Il test alla metacolina nello studio della reattività bronchiale aspecifica in un gruppo di pollinosici.

We have studied thirty subjects sensitive to pollens suffering from seasonal rhinitis and/or mild seasonal asthma. The patients were submitted to a preseasonal and to a seasonal evaluation of their bronchial reactivity by means of a metacholine provocation test in order to measure possible variations of their responsiveness. Our data shown that the metacholine provocation test is not substantially influenced by seasonal pollen stimulation; it is likely that in patients sensitive to pollens, aspecific bronchial reactivity is intermittent, so explaining the inconstant behaviour of responsiveness observed in our allergic patients.

Clinical significance of cholelithiasis in patients with decompensated cirrhosis.

There is general agreement that the prevalence of gallstones in cirrhotics is high (at least twice that in the general population), but the pathogenetic link between cirrhosis and cholelithiasis is still uncertain. The influence of cholelithiasis on survival in cirrhotics is also unknown. During an 8-year period, we observed 90 patients affected by decompensated cirrhosis: 36 of them (40%) turned out by cholecystographic/cholangiographic or ultrasonographic examination to have cholelithiasis. We were not able to demonstrate any correlation between cholelithiasis and sex, age of patients, etiology of cirrhosis, severity of the illness, degree of portal hypertension, previous gastrointestinal bleeding, number of pregnancies, or levels of serum cholesterol, bilirubin, and triglycerides. During the follow-up observation, (range, 1-91 months), 30 patients died. Survival curves analyzed by the log-rank test did not show any difference between patients with or without gallstones. We therefore confirm that cirrhosis is a lithogenic condition, but we were not able to explain the reasons for the close relationship between cholelithiasis and cirrhosis. Gallstones, however, did not affect the survival of these patients.

Normal fibronectin levels after surgical treatment of portal hypertension in liver cirrhosis.

We found a significantly higher plasma fibronectin concentration in a group of nine cirrhotic patients who underwent surgical treatment for portal hypertension (either shunting and non shunting procedures) when compared to twenty non operated patients. Significantly shorter prothrombin time and activated partial thromboplastin time in the operated patients were found as well. These results might be related to an increased breakdown of fibronectin during consumption coagulopathy taking place in the extended collaterals and reversed in part by surgical treatment of portal hypertension complicating liver cirrhosis.