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Biomedical subjects

A Rovira

Publications and source records attributed to A Rovira.

At least 19 recordsLinked to original sources
PubMed2007

Patulin accumulation in apples by Penicillium expansum during postharvest stages.

AIMS: The aim of this study was to assess the opportunities of Penicillium expansum to develop and produce patulin in apples during cold storage and in the steps prior to processing of apple products. METHODS AND RESULTS: Two lots of apples var. Golden with different ripeness degree were used. Half of each lot was fungicide treated. Apples were inoculated with P. expansum and stored at 1 degrees C for 6 weeks. The extent of lesions and patulin accumulation both at the end of cold storage and after 3 days at 20 degrees C were assessed. Short storage at 20 degrees C aimed to simulate the transport and storage steps at room temperature before processing. Lesion size significantly increased during the storage at 20 degrees C. An interaction between fungicide treatment and ripeness degree was found; efficiency of fungicide treatment was higher for ripe apples. Although lesions were evident after cold storage, no patulin was detected. Patulin was detected only when fruits were further stored at 20 degrees C. Neither ripeness degree nor fungicide treatment affected patulin accumulation. CONCLUSIONS: Cold storage periods of 6 weeks do not lead to patulin accumulation. SIGNIFICANCE AND IMPACT OF THE STUDY: Shortening preprocessing times at warm temperatures would result into a reduction in patulin content at initial steps of fruits entering the processing plants.

Food Handling↗
PubMed2006

Baseline MRI predicts future attacks and disability in clinically isolated syndromes.

OBJECTIVE: To determine the relation between baseline MRI and both conversion to multiple sclerosis (MS) and development of disability in a cohort of patients with clinically isolated syndromes (CIS). METHODS: From 1995 to 1998, 175 consecutive patients with CIS underwent brain MRI within 3 months of their first attack and again 12 months and 5 years later. We studied the number and location of lesions at baseline and development of new T2 lesions. We also analyzed conversion to MS and development of disability (Expanded Disability Status Scale [EDSS] > or = 3.0). RESULTS: We included 156 patients with CIS followed for a median of 7 years. Compared to the reference group with 0 Barkhof criteria at baseline MRI, patients with one or two Barkhof criteria showed an adjusted hazard ratio (HR) of 6.1 (2.2 to 16.6) and patients with three to four Barkhof criteria of 17.0 (6.7 to 43) for conversion to MS and differentiated patients with low, medium, and high conversion risk. EDSS at year 5 correlated with baseline number of Barkhof criteria (r = 0.46, p < 0.0001). When categorizing by number of baseline lesions, similar results were seen. Patients with a baseline MRI with three to four Barkhof criteria had an adjusted HR of 3.9 (1.1 to 13.6) for reaching EDSS > or = 3.0. Only 10% of the latter had disability at year 5, but 40% reached this at 8 years. CONCLUSIONS: Baseline MRI determines the risk for converting to clinically definite multiple sclerosis and correlates with disability at 5 years. The proportion of patients developing disability is low during the first 5 years but rapidly increases shortly after.

Adult↗
PubMed2006

Neuromyelitis optica diagnosis in clinically isolated syndromes suggestive of multiple sclerosis.

The authors assessed the extent of overlap between current diagnostic criteria of neuromyelitis optica (NMO) and multiple sclerosis (MS) by applying NMO criteria to a large cohort of 320 patients with clinically isolated syndromes (CIS). Twenty-three (7.2%) patients fulfilled NMO absolute criteria at some time and 1 (0.3%) also fulfilled one major supportive criterion. Therefore, even by systematically applying NMO criteria in patients with CIS, NMO diagnosis is reached infrequently.

Adult↗
PubMed2006

Automatic detection of patients with nosocomial infection by a computer-based surveillance system: a validation study in a general hospital.

OBJECTIVE: To validate an automated system for the detection of patients with nosocomial infection (NI) in an intensive care unit (ICU). DESIGN: Retrospective analysis of data from the hospital information system. We applied 3 different NI suspicion criteria (positive microbiology reports, antibiotic administration, and diagnosis of clinical infection) and compared the results to those of a prospective NI incidence study done in the ICU during the same period (1999-2002). SETTING: A 250-bed general hospital in Barcelona, Spain. PATIENTS: From April 15, 1999, through June 30, 2002, 1380 patients were admitted to the ICU. Of these, 1043 had an ICU stay of more than 24 hours and were included in the study. RESULTS: At least one NI suspicion criterion was present for 242 patients (23.2%); 2 criteria were present for 184 patients (17.6%); and all 3 criteria were present for 112 (11.7%). Comparison of hospital information system data to the results of the prospective study indicated that the combination of 2 criteria demonstrated the most satisfactory sensitivity (94.3%; 95% confidence interval [CI], 79.5%-99.0%) and specificity (83.6%; 95% CI, 76.8%-88.9%). The positive predictive value was 55.9% (95% CI, 42.5%-68.6%); the negative predictive value was 98.5% (95% CI, 94.2%-99.7%). The system could assign a site of infection for 90.4% of the NIs detected. CONCLUSION: The hospital information system was a useful tool for retrospectively detecting patients with an NI during the ICU stay. Given its high sensitivity, it may be useful as an alert for the NI team.

Aged↗
PubMed2006

The proteasome: a novel target for anticancer therapy.

The proteasome is an ubiquituous enzyme complex that plays a critical role in the degradation of many proteins involved in cell cycle regulation, apoptosis and angiogenesis. Since these pathways are fundamental for cell survival and proliferation, particularly in cancer cells, the inhibition of proteasome is an attractive potential anticancer therapy. Bortezomib (Velcade, formerly PS-341) is an extremely potent and selective proteasome inhibitor that shows strong activity in in vitro and in vivo laboratory studies against many solid and hematologic tumor types. Moreover, bortezomib, mainly by inhibition of the NF-kappaB pathway, has a chemosensitizing effect when administered together with other antitumoral drugs. Clinical phase I trials, showed good tolerance of bortezomib at doses that achieved a desired degree of proteasome inhibition. Phase II studies showed high response rates in refractory multiple myeloma patients, which led to the accelerated approval of bortezomib by the Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) for this indication. A phase III trial comparing bortezomib to dexamethasone in refractory/relapsed multiple myeloma patients had to be halted due to a survival advantage in the bortezomib arm. Additional studies are focusing in the potential benefit of bortezomib in newly diagnosed multiple myeloma patients. In other solid and hematological malignancies, phase II studies with bortezomib alone or in combination are ongoing with encouraging results, particularly in lung cancer and lymphoma.

Antineoplastic Agents↗
PubMed2006

[Prevalence and consumption of medication in diabetes mellitus in Madrid (1996-2002)].

OBJECTIVES/AIMS: To determine the prevalence of diabetes mellitus treated with drugs and the prescription of drugs in diabetes (oral anti-diabetics and insulin) in the Community of Madrid between 1996-2002. METHODS: We used the indirect method for estimating the rate of prevalence of diabetes based on antidiabetic drug in the Madrid Community. We studied the consumption or oral antidiabetics (OH) and insulin (IN) in all the Madrid Community Area from 1996 to 2002. To make consumption uniform we used the daily doses/1,000 inhabitants/day (DHD). The total consumption was obtained using the official billing data and the annual population data provided by the "Institute Madrileño de Salud". RESULTS: The prevalence of diabetes mellitus increased 62.5% in the period studied, ranging from 1.6% in 1996 up to 2.6% in 2002. The DHD of oral drugs increased 87.8% from 12.2 in 1996 to 23.07 in 2002. The DHD of insulin decreased 28.2% from 3.99 in 1996 down to 3.11 in 2002. The OH/IN ratio increased 138%, from 3.11 to 7.42 in 2002. There is a tendency to increase biguanide and sulfonilureas with low risk of hypoglycemia. The total cost of insulin and oral medication increase every year, the increase of diabetic patients and the cost/DDD of the new drugs are factors that increase the total cost of diabetes. CONCLUSIONS: The prevalence of diabetes mellitus treated with drugs increased in the Community of Madrid. There is a progressive use of oral drugs versus insulin, and a tendency to prescribe biguanide, sulfonylureas, especially gliclazide and glimepiride. A tendency to substitute insulin with insulin analogues is also seen in the use of insulin. The cost of diabetes increases yearly.

Catchment Area, Health↗
PubMed2006

Activation of nuclear factor-kappa B is linked to resistance to neoadjuvant chemotherapy in breast cancer patients.

The nuclear factor (NF)-kappaB system is a promising anticancer target due to its role in oncogenesis and chemoresistance in preclinical models. To provide evidence in a clinical setting on the role of NF-kappaB in breast cancer, we aimed to study the value of basal NF-kappaB/p65 in predicting resistance to neoadjuvant chemotherapy, and to characterise the pharmacodynamic changes in NF-kappaB/p65 expression following chemotherapy in patients with locally advanced breast cancer. Pre- and post-chemotherapy tumour specimens from 51 breast cancer patients treated with anthracycline- and/or taxane-containing neoadjuvant chemotherapy were assayed by immunohistochemistry for NF-kappaB/p65 subcellular expression. We studied NF-kappaB/p65, a well-characterised member of the NF-kappaB family that undergoes nuclear translocation when NF-kappaB is activated. Activation of NF-kappaB (i.e. nuclear NF-kappaB/p65 staining in pre-therapy specimens) was linked to chemoresistance. Patients with NF-kappaB/p65 nuclear staining in pre-treatment samples had a 20% clinical response rate, while patients with undetected nuclear staining had a 91% response rate to chemotherapy (P = 0.002). Notably, four patients achieved a complete histological response and none of them had pre-treatment NF-kappaB/p65 nuclear staining. Moreover, the number of patients with NF-kappaB/p65 activation increased after chemotherapy exposure. It is concluded that NF-kappaB/p65 activation assayed by immunohistochemistry is a predictive factor of resistance to neoadjuvant chemotherapy in breast cancer patients. Moreover, NF-kappaB activation was inducible following chemotherapy in a proportion of breast cancer patients. These novel clinical findings strengthen the rationale for the use of NF-kappaB inhibitors to prevent or overcome chemoresistance in breast cancer.

Adult↗
PubMed2005

Activation of nuclear factor-kappaB in human prostate carcinogenesis and association to biochemical relapse.

Nuclear factor (NF)-kappaB/p65 regulates the transcription of a wide variety of genes involved in cell survival, invasion and metastasis. We characterised by immunohistochemistry the expression of NF-kappaB/p65 protein in six histologically normal prostate, 13 high-grade prostatic intraepithelial neoplasia (PIN) and 86 prostate adenocarcinoma specimens. Nuclear localisation of p65 was used as a measure of NF-kappaB active state. Nuclear localisation of NF-kappaB was only seen in scattered basal cells in normal prostate glands. Prostatic intraepithelial neoplasias exhibited diffuse and strong cytoplasmic staining but no nuclear staining. In prostate adenocarcinomas, cytoplasmic NF-kappaB was detected in 57 (66.3%) specimens, and nuclear NF-kappaB (activated) in 47 (54.7%). Nuclear and cytoplasmic NF-kappaB staining was not correlated (P=0.19). By univariate analysis, nuclear localisation of NF-kappaB was associated with biochemical relapse (P=0.0009; log-rank test) while cytoplasmic expression did not. On multivariate analysis, serum preoperative prostate specific antigen (P=0.02), Gleason score (P=0.03) and nuclear NF-kappaB (P=0.002) were independent predictors of biochemical relapse. These results provide novel evidence for NF-kappaB/p65 nuclear translocation in the transition from PIN to prostate cancer. Our findings also indicate that nuclear localisation of NF-kappaB is an independent prognostic factor of biochemical relapse in prostate cancer.

Adenocarcinoma↗
PubMed2005

Long-term clinical outcome of primary progressive MS: predictive value of clinical and MRI data.

The authors sought to identify clinical and MRI predictors of outcome in primary progressive multiple sclerosis (PPMS). Clinical and MRI assessments were performed at baseline and 2 and 5 years (clinical only). At baseline, disease duration, expanded disability status scale (EDSS) and brain volume predicted outcome. Adding short-term change variables, baseline EDSS, changes in T2* lesion load and cord area, and number of new lesions were predictive. Clinical and MRI variables predict long-term outcome in PPMS.

Atrophy↗
PubMed2005

Distribution territories and causative mechanisms of ischemic stroke.

Ischemic stroke prognosis, risk of recurrence, clinical assessment, and treatment decisions are influenced by stroke subtype (anatomic distribution and causative mechanism of infarction). Stroke subtype diagnosis is better achieved in the early phase of acute ischemia with the use of multimodal MR imaging. The pattern of brain lesions as shown by brain MR imaging can be classified according to a modified Oxfordshire method, based on the anatomic distribution of the infarcts into six groups: (1) total anterior circulation infarcts, (2) partial anterior circulation infarcts, (3) posterior circulation infarcts, (4) watershed infarcts, (5) centrum ovale infarcts, and (6) lacunar infarcts. The subtype of stroke according to its causative mechanism is based on the TOAST method, which classifies stroke into five major etiologic groups: (1) large-vessel atherosclerotic disease, (2) small-vessel atherosclerotic disease, (3) cardioembolic source, (4) other determined etiologies, and (5) undetermined or multiple possible etiologies. The different MR imaging patterns of acute ischemic brain lesions visualized using diffusion-weighted imaging and the pattern of vessel involvement demonstrated with MR angiography are essential factors that can suggest the most likely causative mechanism of infarction. This information may have an impact on decisions regarding therapy and the performance of additional diagnostic tests.

Acute Disease↗
PubMed2005

Preclinical and clinical development of the proteasome inhibitor bortezomib in cancer treatment.

The proteasome is a ubiquitous enzyme complex that plays a critical role in the degradation of many proteins involved in cell cycle regulation, apoptosis and angiogenesis. Since these pathways are fundamental for cell survival and proliferation, particularly in cancer cells, the inhibition of proteasome is an attractive potential anticancer therapy. The present review will focus on the proteasome inhibitor bortezomib (Velcade, formerly PS-341; Millennium Pharmaceuticals, Inc., Cambridge, MA, USA). Bortezomib is an extremely potent and selective proteasome inhibitor that shows strong activity in in vitro and in vivo laboratory studies against many solid and hematologic tumor types. Moreover, bortezomib, mainly by inhibition of the NF-kappaB pathway, has a chemosensitizing effect when administered together with other antitumoral drugs. Based on these results, bortezomib entered clinical phase I trials, alone or in combination with chemotherapy, that showed good tolerance at doses that achieved a desired degree of proteasome inhibition. Phase II studies showed high response rates in refractory multiple myeloma patients, which led to the accelerated approval of bortezomib by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) for this indication. A phase III trial comparing bortezomib with dexamethasone in refractory/ relapsed multiple myeloma patients had to be halted due to a survival advantage in the bortezomib arm. Additional studies are focusing on the potential benefit of bortezomib in newly diagnosed multiple myeloma patients. In other solid and hematological malignancies, phase II studies with bortezomib alone or in combination with other agents are ongoing. Encouraging results, particularly in lung cancer and lymphoma, have been observed. The critical molecules or genes responsible for tumor sensitivity to bortezomib continue to be evaluated using novel technologies.

Animals↗
PubMed2004

High lipoprotein (a), diabetes, and the extent of symptomatic intracranial atherosclerosis.

BACKGROUND: Lipoprotein (a) (Lp[a]) has important atherothrombogenic properties, but its role in intracranial atherosclerosis remains unclear. OBJECTIVE: To investigate the relationship between Lp(a) level and the extent of intracranial large-artery occlusive disease. METHODS: Between June 2001 and August 2003, 166 consecutive first-ever TIA or stroke patients had intracranial stenoses on transcranial Doppler, of which 100 fulfilled all inclusion criteria. The extent of intracranial large-artery occlusive disease was assessed by the number of angiographically confirmed intracranial stenoses. Serum Lp(a) was determined a minimum of 3 months after stroke onset. RESULTS: Two hundred eighty-one intracranial stenoses were documented. Fifty-one (51%) patients had three or more stenoses (greater-extent group). Patients in the highest Lp(a) quartile had a higher adjusted odds ratio (OR) for a greater extent than those in the lowest quartile (OR 3.43, 95% CI 1.04 to 11.33, p = 0.04). A positive correlation was found between Lp(a) concentration and the number of stenoses (r = 0.310, p = 0.002). Moreover, Lp(a) level increased gradually with the number of stenoses (p = 0.02). A multiple logistic regression model identified diabetes (OR 2.4, 95% CI 1.04 to 5.57, p = 0.04) and high Lp(a) (OR 2.52, 95% CI 1.03 to 6.18, p = 0.043) as independent markers of a greater extent of intracranial large-artery occlusive disease. CONCLUSIONS: High Lp(a) level and diabetes mellitus are independent markers of a greater extent of intracranial large-artery occlusive disease. These findings support a role for Lp(a) in intracranial stenotic atherogenesis and might be useful for the selection of high-risk patients.

Aged↗
PubMed2004

Decreased MMP-9 production in primary progressive multiple sclerosis patients.

BACKGROUND: An increase in MMP-9 levels has been found in relapsing-remitting (RR) multiple sclerosis (MS) showing correlation with magnetic resonance (MR) parameters mainly during relapses. However, data regarding primary progressive (PP) MS is scarce. OBJECTIVES: To determine both the pro and active forms of MMP-9 in PPMS and transitional progressive (TP) MS, RRMS and healthy controls (HC), and to assess the relationship between MMP-9 levels and clinical and radiological variables in PP/TPMS. METHODS: 73 patients with PP/TPMS, 50 RRMS and 43 HC were studied. Levels of pro and active forms of MMP-9 in serum were measured with ELISA. EDSS and MSFC scores were recorded and T2- and T1-weighted MR scans were obtained at the time of blood sampling and one and two years later for PP/TP MS cases. RESULTS: MMP-9 levels were 202.27 ng/ml for PP/TPMS, 242.20 ng/ml for RRMS and 274.49 ng/ml for HC. MMP-9 levels were significantly lower in PP/TPMS compared to RRMS (P= 0.026) and HC (P= 0.001). No significant correlations were found between MMP-9 levels and clinical scores or radiological parameters. CONCLUSIONS: These results point to different regulatory mechanisms of MMP-9 production and/or activity between PP/TPMS and RRMS.

Adult↗
PubMed2003

New diagnostic criteria for multiple sclerosis: application in first demyelinating episode.

BACKGROUND: Recently developed diagnostic criteria for MS (McDonald criteria) indicate that in patients with a single demyelinating episode (clinically isolated syndromes [CIS]), evidence for dissemination in space and time, essential for diagnosis, may be provided by MRI. OBJECTIVE: To assess the usefulness of these new criteria in patients with CIS suggestive of MS. METHODS: A total of 139 patients with CIS followed for a median of 3 years underwent brain MRI within 3 months of their first attack and again 12 months later. The number and location of lesions at baseline, the development of new lesions at follow-up, and the results of CSF examination (which, if positive, requires fewer MR abnormalities for diagnosis) were analyzed. The new McDonald criteria (incorporating MRI) were compared to the existing Poser diagnostic criteria and their accuracy was evaluated. RESULTS: At 12 months, 11% had clinically definite MS according to the Poser criteria compared to 37% with the McDonald criteria. Eighty percent of patients fulfilling these new criteria developed a second clinical episode within a mean follow-up of 49 months. The new criteria showed a sensitivity of 74%, specificity of 86%, and accuracy of 80% in predicting conversion to clinically definite MS. CONCLUSION: One year after symptom onset, more than three times as many patients with CIS were diagnosed with MS using new diagnostic criteria incorporating MRI results compared to older criteria. However, the proposed MRI criteria require further prospective studies to optimize sensitivity and specificity.

Adolescent↗
PubMed2003

Retrospective study on porcine circovirus type 2 infection in pigs from 1985 to 1997 in Spain.

A retrospective survey was performed to detect lesions of Postweaning multisystemic wasting syndrome (PMWS) and nucleic acid of porcine circovirus type 2 (PCV2) in archived formalin-fixed, paraffin-embedded tissues from 189 pigs, and antibodies to this virus in sera of 388 pigs from the Spanish livestock between the years 1985 and 1997. PCV2 nucleic acid was detected by in situ hybridization (ISH) in tissues from 78 of 189 (41.3%) examined pigs. Variable amount of viral genome was detected in association with slight to severe microscopic lymphoid lesions consisting of lymphocyte depletion and histiocytic infiltration. The first positive case of PMWS with typical lesions and ISH positive corresponded to a pig necropsied in 1986. Two hundred and eighty-two of 388 (72.7%) sera were positive by immunoperoxidase monolayer assay. Serological and pathological data of the present study indicate that PCV2 was a enzootic infection in Spain since 1985, suggesting that the introduction of this virus in the livestock occurred previously.

Animals↗
PubMed2003

Conversion to multiple sclerosis after a clinically isolated syndrome of the brainstem: cranial magnetic resonance imaging, cerebrospinal fluid and neurophysiological findings.

BACKGROUND AND AIM: Conversion to multiple sclerosis (MS) after optic neuritis and myelitis has been thoroughly studied; however, limited data are available regarding conversion to MS after a clinically isolated syndrome of the brainstem (CISB). The aim of this study was to investigate conversion to MS in patients with CISB. METHODS: Fifty-one patients with CISB were prospectively studied. Cranial magnetic resonance imaging (MRI), determination of oligoclonal bands (OBs) in the cerebrospinal fluid (CSF) and evoked potentials (EPs) were performed. Based on conversion to MS at follow-up, the sensitivity, specificity, accuracy and positive and negative predictive values of these tests were calculated. RESULTS: Clinically definite MS developed in 18 (35%) patients after a mean follow-up of 37 months. Paty's MRI criteria showed a sensitivity of 89%, a specificity of 52% and an accuracy of 65%; Fazekas' criteria showed a sensitivity of 89%, a specificity of 48% and an accuracy of 63%; Barkhof's criteria showed a sensitivity of 78%, a specificity of 61% and an accuracy of 67%. The presence of OBs in the CSF showed a sensitivity of 100%, a specificity of 42% and an accuracy of 63%. No differences for neurophysiological parameters were found between patients who did and those who did not convert to MS. CONCLUSION: Fulfilling Paty's, Fazekas' or Barkhof's MRI criteria and the presence of OBs in the CSF are associated with a higher risk of conversion to MS in patients with CISB. Determination of OBs in the CSF has the greatest sensitivity of all tests. Barkhof's MRI criteria have greater specificity (although less than previously published for mixed cohorts of clinically isolated syndromes) in predicting conversion to MS for CISB than either Paty's or Fazekas' criteria.

Adolescent↗