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Biomedical subjects

C Serra

Publications and source records attributed to C Serra.

At least 37 records · Page 2Linked to original sources

Multiple sclerosis complexity in selected populations: the challenge of Sardinia, insular Italy.

Several lines of evidence indicate a genetic contribution to multiple sclerosis (MS) both in terms of predisposition to the disease and of immunological mechanisms which are known to play crucial roles in MS pathogenesis. The presence of high- and low-risk areas for MS in neighbouring regions supports the theory that MS predisposition is influenced by a complex interaction of genetic and environmental factors. Therefore, the use of genetically homogeneous and geographically isolated populations becomes an increasing requirement to reduce biasing biological variables. Sardinians fulfil these conditions well because of their different phylogeny from Europeans and the unique selective pressures which shaped their genome. Sardinians display amongst the highest MS prevalence rates world-wide and increasing MS incidence rates over time. Also, MS in Sardinia is linked to distinct human leucocyte antigen (HLA) alleles and associated to different patterns of cytokine production from lymphoid cells of different HLA subtypes. In this context, recent findings and future perspectives on the peculiarities of Sardinian MS concerning genetic, immunological and epidemiological aspects are presented. So far, our results indicate that variations at the level of territorial distribution and HLA-association are present which render MS heterogeneous even in this ethnically homogeneous population.

Humans↗

ADP and other metabolites released from Acanthamoeba castellanii lead to human monocytic cell death through apoptosis and stimulate the secretion of proinflammatory cytokines.

Monocytes/macrophages are thought to be involved in Acanthamoeba infections. The aim of this work was to study whether soluble metabolites (ADP and other compounds) released by Acanthamoeba castellanii trophozoites could induce morphological and biochemical changes in human monocytic cells in vitro. We demonstrate here that ADP constitutively released in the medium by A. castellanii, interacting with specific P2y(2) purinoceptors expressed on the monocytic cell membrane, caused a biphasic rise in [Ca(2+)](i), morphological changes characteristics of cells undergoing apoptosis, caspase-3 activation, and secretion of tumor necrosis factor alpha (TNF-alpha). The same results were found in monocytes exposed to purified ADP. Cell damage and TNF-alpha release induced by amoebic ADP were blocked by the P2y(2) inhibitor suramin. Other metabolites contained in amoebic cell-free supernatants, with molecular masses of, respectively, >30 kDa and between 30 and 10 kDa, also caused morphological modifications and activation of intracellular caspase-3, characteristics of programmed cell death. Nevertheless, mechanisms by which these molecules trigger cell damage appeared to differ from that of ADP. In addition, other amoebic thermolable metabolites with molecular masses of <10 kDa caused the secretion of interleukin-1beta. These findings suggest that pathogenic free-living A. castellanii by release of ADP and other metabolites lead to human monocytic cell death through apoptosis and stimulate the secretion of proinflammatory cytokines.

Acanthamoeba↗

Second-line chemotherapy for non-small cell lung cancer.

BACKGROUND: The role of second-line chemotherapy for the treatment of patients with non-small cell lung cancer (NSCLC) who have relapsed or failed to respond to first-line treatment was unclear. OBJECTIVES: To determine the effectiveness of any second-line chemotherapy in patients with NSCLC. SEARCH STRATEGY: Bibliographic databases were searched. Handsearching and contact with experts was also performed. SELECTION CRITERIA: Randomised controlled clinical trials in which any second-line chemotherapy was compared with BSC in patients with NSCLC who had previously failed to any previous chemotherapy regimen. DATA COLLECTION AND ANALYSIS: Data was extracted by 2 independent reviewers and revised by all authors. MAIN RESULTS: Only one study was included. It randomised 204 patients to receive either doxetaxel or BSC. Following an unacceptably high toxic death rate the dose of doxetaxel was reduced from 100 mg/m(2) to 75 mg/m(2). Doxetaxel gave an extra 2.4 months of survival - an average of 7.0 months vs 4.6 months on BSC. At 1 year after diagnosis 29% of doxetaxel treated patients were alive compared with 19% of the BSC group. REVIEWER'S CONCLUSIONS: Definitive recommendations cannot be made since evidence is only available from one randomised controlled trial which, though of reasonable quality, had a number of limitations. There is currently no evidence to support second-line treatment of patients with poor performance status. Larger, well-designed controlled trials are needed to further evaluate whether the benefits of second-line chemotherapy to patients with NSCLC outweigh its risks and costs.

Antineoplastic Agents, Phytogenic↗

Multiple sclerosis and multiple sclerosis-associated retrovirus in Sardinia.

The island of Sardinia has a high and increasing incidence of multiple sclerosis (MS). In a search for environmental factors that may account for this anomalously high incidence, we looked for evidence of multiple sclerosis-associated retrovirus (MSRV) that has previously been found in the plasma and cerebrospinal fluid of MS patients. We studied 25 MS patients and 25 matched healthy controls of ascertained Sardinian lineage. Blood samples were processed for extracellular RNA extraction. RNAs underwent reverse transcription/nested polymerase chain reaction (RT-PCR) with primers specific for MRSV-pol gene. We found a striking correlation between MSRV positivity and MS disease, but the virus was found also only in controls (100% and 12% respectively; Fisher's exact test, p<0.00001). It is unclear whether MSRV exerts any pathogenic role in MS. It is possible that this is simply an epiphenomenon, but even then, it may constitute a diagnostic marker.

Female↗

Lysozyme expression by breast carcinomas, correlation with clinicopathologic parameters, and prognostic significance.

BACKGROUND: Here we evaluate the expression and prognostic value of lysozyme, a milk protein that is also synthesized by a significant percentage of breast carcinomas, in women with breast cancer. METHODS: Lysozyme expression was examined by immunohistochemical methods in a series of 177 breast cancer tissue sections. Staining was quantified by using the HSCORE system, which considers both the intensity and the percentage of cells staining at each intensity. The prognostic value of lysozyme was retrospectively evaluated by multivariate analysis that took into account conventional prognostic factors. RESULTS: A total of 126 of 177 carcinomas (69.4%) stained positive for this protein, but there were clear differences among them with regard to the intensity and percentage of stained cells. Lysozyme values were higher in well-differentiated and moderately differentiated tumors than in poorly differentiated tumors (P < .05). Similarly, lysozyme levels were higher in small and node-negative tumors than in large and node-positive tumors (P < .05). Moreover, results indicated that low lysozyme content predicted shorter relapse-free survival and overall survival (P < .005). Separate Cox multivariate analysis in subgroups of patients as defined by node status showed that lysozyme expression was an independent prognostic factor able to predict both relapse-free survival and overall survival in node-negative patients (P < .05). CONCLUSIONS: Tumoral expression of lysozyme is associated with lesions of favorable evolution in breast cancer. This milk protein may be a new prognostic factor in patients with breast cancer.

Adult↗

[Preoperative serum levels of the carcinoembryonic antigen (CEA) and prognosis in colorectal cancer].

OBJECTIVE: To analyze the prognostic value of the preoperative serum levels of the carcinoembryonic antigen (CEA) in primary colorectal carcinoma. MATERIAL AND METHODS: Preoperative serum levels of CEA were analyzed in 275 colorectal cancer patients, who were followed up for a minimum of 5 years, or until death. RESULTS: The percentage of positivities for the preoperative serum levels of CEA (> 6 ng/ml) was positively and significantly associated with the tumoral stage (A: 10,5%; B: 38,8%; C: 32,2%; y D: 72%; p < 0,0001). In addition, the elevated serum values of the antigen were significantly associated, in the univariate analysis, with short survival in the overall group of patients (p < 0,0001). However, the multivariate analysis only showed an independent prognosis value of the CEA in the subgroup of patients with stage C tumors. CONCLUSIONS: Preoperative serum levels of CEA may be useful to predict tumoral extension, and also for the prognosis regarding stage C colorectal cancer patients.

Adenocarcinoma↗

Value of splanchnic Doppler ultrasound in the diagnosis of portal hypertension.

The accuracy of various Doppler parameters of portal circulation in the diagnosis of relevant portal hypertension (presence of gastroesophageal varices) was prospectively validated. The following parameters were compared in 51 patients with chronic liver disease (40 with cirrhosis and 11 with chronic hepatitis): portal vein flow velocity and congestion index, hepatic and splenic arteries resistance indexes (RI), modified liver vascular index (portal flow velocity/hepatic artery RI) and portal hypertension index, a new index calculated as: [(hepatic artery RI x 0.69) x (splenic artery RI x 0.87)]/portal vein flow velocity. Highest accuracy was achieved by the splenic artery RI and the portal hypertension index (both around 75%) at cut-offs, respectively, of 0.60 and 12 cm/s(-1), which appeared to be, therefore, the most favorable parameters for the clinical practice. Their use may limit the need for endoscopy to search for varices.

Adult↗

The contribution of cigarette smoking to bladder cancer in women (pooled European data).

BACKGROUND: Using a combined analysis of 11 case-control studies from Europe, we have investigated the relationship between cigarette smoking and bladder cancer in women. METHODS: Available smoking information on 685 female bladder cancer cases and 2416 female controls included duration of smoking habit, number of cigarettes smoked per day, and time since cessation of smoking habit for ex-smokers. RESULTS: There was an increasing risk of bladder cancer with increasing duration of smoking, ranging from approximately a two-fold increased risk for a duration of less than 10 years (odds ratio (OR) = 1.9, 95% confidence interval (CI) 1.1-3.1) to over a four-fold increased risk for a duration of greater than 40 years (OR = 4.1, 95% CI 3.0-5.5). A dose-response relationship was observed between number of cigarettes smoked per day and bladder cancer up to a threshold limit of 15-20 cigarettes per day, OR = 3.8 (95% CI 2.7-5.4), after which no increased risk was observed. An immediate decrease in risk of bladder cancer was observed for those who gave up smoking. This decrease was over 30% in the immediate 1-4 years after cessation, OR = 0.68 (95% CI 0.38-1.2). However, even after 25 years the decrease in risk did not reach the level of the never-smokers, OR = 0.27 (95% CI 0.21-0.35). CONCLUSION: The proportion of bladder cancer cases among women attributable to ever smoking was 0.30, (0.25-0.35) and to current smoking was 0.18 (0.14-0.22). These attributable proportions are less than those observed among men, although they are likely to increase in the future as the smoking-related disease epidemic among women matures.

Adult↗

Cigar, pipe, and cigarette smoking and bladder cancer risk in European men.

OBJECTIVE: Estimating the risk of bladder cancer from cigar and pipe smoking is complicated by a small number of non-cigarette smokers included in most relevant studies. METHODS: We undertook a pooled analysis of the data on men from six published case-control studies from Denmark, France, Germany, and Spain, to assess the association between pipe and cigar smoking and bladder cancer, and to compare it with the risk from cigarette smoking. Complete history of tobacco smoking was ascertained separately for cigarettes, cigars, and pipe. Odds ratios (ORs) were estimated after adjusting for age, study, and employment in high-risk occupations. RESULTS: The pooled data set comprised 2279 cases and 5268 controls, of whom 88 cases and 253 controls smoked only cigars or pipe. The OR for pure cigarette smoking was 3.5 (95% confidence interval [CI] 2.9-4.2), that for pure pipe smoking was 1.9 (95% CI 1.2-3.1) and that for pure cigar smoking was 2.3 (95% CI 1.6-3.5). The increase in the OR of bladder cancer that was observed with duration of smoking was non-significantly lower for cigars than for cigarettes. CONCLUSION: Our results suggest that smoking of cigars and pipe is carcinogenic to the urinary bladder, although the potency might be lower than for cigarettes.

Case-Control Studies↗

Cigarette smoking and bladder cancer in men: a pooled analysis of 11 case-control studies.

The primary risk factor for bladder cancer is cigarette smoking. Using a combined analysis of 11 case-control studies, we have accurately measured the relationship between cigarette smoking and bladder cancer in men. Available smoking information on 2,600 male bladder cancer cases and 5,524 male controls included duration of smoking habit, number of cigarettes smoked per day and time since cessation of smoking habit for ex-smokers. There was a linear increasing risk of bladder cancer with increasing duration of smoking, ranging from an odds ratio (OR) of 1.96 after 20 years of smoking (95% confidence interval [CI] 1.48-2.61) to 5.57 after 60 years (CI 4.18-7.44). A dose relationship was observed between number of cigarettes smoked per day and bladder cancer up to a threshold limit of 15-20 cigarettes per day, OR = 4.50 (CI 3.81-5. 33), after which no increased risk was observed. An immediate decrease in risk of bladder cancer was observed for those who gave up smoking. This decrease was over 30% after 1-4 years, OR = 0.65 (0. 53-0.79), and was over 60% after 25 years of cessation, OR = 0.37 (0. 30-0.45). However, even after 25 years, the decrease in risk did not reach the level of the never-smokers, OR = 0.20. (0.17-0.24). The proportion of bladder cancer cases attributable to ever-smoking was 0.66 (0.61-0.70) for all men and 0.73 (0.66-0.79) for men younger than 60. These estimates are higher than previously calculated.

Adult↗

Interventions for preventing tobacco smoking in public places.

BACKGROUND: Environmental tobacco smoke is a health hazard. Reducing exposure to tobacco smoke in public places is a widespread public health goal. There is, however, considerable variation in the extent to which this goal has been achieved in different settings and societies. There is therefore a need to identify effective strategies for reducing tobacco consumption in public places. OBJECTIVES: To evaluate the effectiveness of interventions to reduce tobacco consumption in public places. SEARCH STRATEGY: We searched the Tobacco Addiction Review Group trials register, Medline, EMBASE, HEALTHSTAR, PAIS, and CDP File (National Centre for Chronic Disease Prevention and Health Promotion, CDC) "Smoking and Health database". We handsearched a key journal and abstracts from international conferences on tobacco. We checked the bibliographies of identified studies and reviews for additional references. SELECTION CRITERIA: We considered randomized and controlled trials, controlled before and after studies and interrupted time series, and uncontrolled before and after studies. We considered strategies aimed at populations, including education campaigns, written material, non-smoking and warning signs, and comprehensive strategies. We also considered strategies aimed at individual smokers. DATA COLLECTION AND ANALYSIS: Information relating to the characteristics and content of all kinds of interventions, participants, outcomes and methods of the study was abstracted by one reviewer and checked by two others. Studies were combined using qualitative narrative synthesis. MAIN RESULTS: Eleven of 22 studies reporting information about interventions to reduce smoking in public places met all the inclusion criteria. All included studies were uncontrolled before and after studies. The most effective strategies used comprehensive, multicomponent approaches to implement policies banning smoking within institutions. Less comprehensive strategies, such as posted warnings and educational material had a moderate effect. Five studies showed that prompting individual smokers had an immediate effect, but such strategies are unlikely to be acceptable as a public health intervention. REVIEWER'S CONCLUSIONS: Carefully planned and resourced, multicomponent strategies effectively reduced smoking within public places. Less comprehensive strategies were less effective. All the studies used relatively weak experimental designs. Most studies were done in the USA, and there is a need to identify ways in which these strategies can be adopted and used in countries with different attitudes to tobacco use. Future studies should also consider the use of more rigorous experimental designs.

Humans↗

Home intravenous antibiotics for cystic fibrosis.

BACKGROUND: Recurrent endobronchial infection in cystic fibrosis requires treatment with intravenous antibiotics for several weeks, which is usually administered in hospital, affecting health costs and quality of life for patients and their families. It is not known whether patients receiving intravenous treatment at home have better or equivalent health outcomes, if costs are reduced or if it is preferred than in-hospital treatment. Home treatment requires training to patients and carers and usually needs a few previous days in hospital. OBJECTIVES: To determine whether home intravenous antibiotic therapy in cystic fibrosis is as effective as in-patient intravenous antibiotic therapy and if it is preferred by patients and/or families. SEARCH STRATEGY: References to trials were obtained from the specialist cystic fibrosis trials register held by the editorial base of the Cochrane Cystic Fibrosis and Genetic Disorders Group. Handsearching of the abstracts books of all Spanish Conferences on cystic fibrosis and the last European Conference (Stockholm, 2000) was carried out by authors. SELECTION CRITERIA: Randomised controlled trials where home intravenous antibiotic treatment for patients with cystic fibrosis was compared with in-hospital intravenous antibiotic treatment, including adults and children with cystic fibrosis. All kinds of antibiotics and regimens administered intravenous were included. DATA COLLECTION AND ANALYSIS: Three reviewers independently selected the trials to be included in the review, assessed methodological quality of each trial and extracted data using a standardised form. Because of several limitations, narrative synthesis was used at this stage. MAIN RESULTS: One study was included with 17 patients aged 10 to 41 years with an infective exacerbation by Pseudomonas aeruginosa. All their 31 admissions were analysed as independent events. Outcomes were measured at 21 days of follow-up after initiation of treatment. Home patients had fewer investigations performed than hospital patients (p<0.002) and general activity was higher in the home group. No differences were found for clinical outcomes, adverse events, complications of intravenous lines or line changes or time to next admission. Home patients received less low-dose home maintenance antibiotic. Quality of life measures showed no differences for dyspnoea and emotional state, but fatigue and mastery were worse for home patients, possibly due to a higher general activity and need of support. Personal, family, sleeping and eating disruptions were less important for home than hospital admissions. Home therapy was cheaper for families and the hospital. Indirect costs were not determined. REVIEWER'S CONCLUSIONS: The current evidence is restricted to one small study. It suggests that in the short term home therapy does not harm patients and in general reduces social disruptions. The decision to attempt home treatment should be based on an individual basis and appropriate local resources. More research is urgently required.

Adult↗

Coffee consumption and bladder cancer in nonsmokers: a pooled analysis of case-control studies in European countries.

BACKGROUND: Coffee consumption has been associated with an excess bladder cancer risk, but results from epidemiological studies are inconsistent. This association has been long debated, in part due to the potential confounding by smoking. We examined the risk associated with coffee consumption in nonsmokers in a pooled analysis of ten European bladder cancer case-control studies. METHODS: The pooled data set comprises 564 cases and 2929 hospital or population controls who had never smoked. They were enrolled in ten studies conducted in Denmark, Germany, Greece, France, Italy and Spain. Information on coffee consumption and occupation was re-coded following standard criteria. Unconditional logistic regression was applied adjusting for age, study center, occupation and gender. RESULTS: Seventy-nine percent of the study population reported having drunk coffee, and 2.4% were heavy drinkers, reporting having drunk on average ten or more cups per day. There was no excess risk in ever coffee drinkers (OR = 1.0, 95% CI 0.8-1.3) compared to never drinkers. The risk did not increase monotonically with dose but a statistically significant excess risk was seen for subjects having drunk ten or more cups per day (OR = 1.8, 95% CI 1.0-3.3). This excess was seen in both men and women. There was no evidence of an association of the risk with duration or type of coffee consumption. The pooled results were not dependent on the findings of any specific study, but they depended on the type of controls with an overall excess risk observed only for studies using hospital controls. CONCLUSION: Nonsmokers who are heavy coffee drinkers may have a small excess risk of bladder cancer. Although these results cannot be attributed to confounding by smoking, the possibility of bias in control selection cannot be discarded. On the basis of these results, only a very small proportion of cancers of the bladder among nonsmokers could be attributed to coffee drinking.

Bias↗

Gallstone ileus in Caroli's disease.

This report describes a patient with a type II Caroli' s disease who developed a gallstone ileus. Previous hepaticojejunostomy operations were thought to have facilitated the migration of stones into the bowel and consequent gallstone ileus. This complication, which was strongly suspected from the clinical history, was diagnosed by ultrasound examination despite the absence of aberrantly located stones on plain abdominal x-ray. Ultrasound is useful in the diagnostic workup of patients with bowel obstruction to confirm obstruction itself, to assess its level, and possibly to identify the cause.

Caroli Disease↗

Assessment of vascular patterns of small liver mass lesions: value and limitation of the different Doppler ultrasound modalities.

OBJECTIVES: This study aimed to investigate the value and limitation of the different Doppler ultrasound modalities (spectral analysis, color, and power Doppler imaging) in the differential diagnosis of small liver tumors to identify the optimal diagnostic approach with the presently available Doppler technology. METHODS: Presence and distribution of color and power Doppler signals, Doppler peak frequency, resistive index, and systolic acceleration time were examined in 133 liver nodules (< or = 4 cm). RESULTS: Color and power Doppler did not identify specific diagnostic vascular patterns. By discriminant analysis, peak frequency (cut-off 1320 Hz) differentiates small hematocellular carcinoma (< or = 2 cm) from macroregenerative nodules and hemangiomas (accuracy 92.6%); resistive index (cut-off 0.65) differentiates malignancies from benign lesions (accuracy 83.8%); and systolic acceleration time (cut-off 105 ms) differentiates hepatocellular carcinoma from metastases (accuracy 80.9%). CONCLUSIONS: Power Doppler imaging is able to assess vascularity in the majority of small liver nodules, but the pattern distribution of tumoral vascular signals does not provide reliable differential diagnostic criteria. Using conventional Doppler technology, power Doppler should be used to detect vascular signals and spectral analysis, and subsequently to measure quantitative parameters such as high peak frequency and resistive index (which identify malignancy) and prolonged systolic acceleration time (which identifies primary from metastatic liver tumors).

Carcinoma, Hepatocellular↗