SIT with a depigmented, polymerized mite extract.
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Biomedical subjects
Publications and source records attributed to A Ferrer.
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BACKGROUND: The purpose of this study was to identify prognostic parameters for patients with follicular lymphoma (FL) in first progression/relapse. These would be useful for selection of high-risk patients for inclusion in trials aimed at determining the effect of new treatment approaches in such patients. PATIENTS AND METHODS: Ninety patients (48 male, 42 female, median age 56 years) diagnosed with FL, in a single institution during a 20 year period and relapsing/progressing after an initial response to therapy, were recruited. The main end-point of the study was survival from progression (SFP). Univariate and multivariate analyses were performed, including among the predictive variables the response duration (RD) after the initial treatment and the main features of the patients at the first progression or relapse. RESULTS: Five-year SFP was 47% (95% confidence interval 35% to 58%). Patients with RD following initial therapy >2 years had a longer SFP (5-year SFP 63 versus 33%, P = 0.012). Other variables with prognostic interest for SFP were stage at diagnosis and the following variables at relapse: age, bulky disease, performance status, serum lactate dehydrogenase level, serum beta2-microglobulin level, bone marrow involvement, stage and International Prognostic Index rating. In the multivariate analysis, poor performance status at progression and a RD <2 years were the most important unfavorable variables to predict SFP. CONCLUSION: In patients with FL, RD along with performance status at progression are features that predict SFP. These variables could thus be useful to select candidates for experimental treatments.
BACKGROUND: A reduction in expiratory muscle (ExM) endurance in patients with chronic obstructive pulmonary disease (COPD) may have clinically relevant implications. This study was carried out to evaluate ExM endurance in patients with COPD. METHODS: Twenty three patients with COPD (FEV(1) 35 (14)% predicted) and 14 matched controls were studied. ExM endurance was assessed using a method based on the use of an expiratory threshold valve which includes two steps. In step 1 the load is progressively increased (50 g every 2 minutes) until task failure is reached, and the pressure generated against the highest tolerated load is defined as the maximal expiratory sustainable pressure (Pthmax). In step 2 subjects breathe against a submaximal constant load (80% of Pthmax) and the time elapsed until task failure is termed the expiratory endurance time (Tth(80)). In addition, the strength of peripheral muscles (handgrip, HGS) and respiratory muscles (maximal inspiratory and expiratory pressures, PImax and PEmax, respectively) was evaluated. RESULTS: Patients with COPD had lower ExM strength and endurance than controls: PEmax 64 (19)% predicted v 84 (14)% predicted (mean difference 20%; 95% confidence intervals (CI) 14 to 39); Pthmax 52 (27) v 151 (46) cm H(2)O (mean difference 99, 95% CI 74 to 123); and Tth(80) 9.4 (6.3) v 14.2 (7.4) min (mean difference 4.8, 95% CI 1.0 to 10.4; p<0.01 for all). Interestingly, ExM endurance directly correlated with both the severity of airways obstruction (Pthmax with FEV(1), r=0.794, p<0.01) and the reduction in strength observed in different muscle groups (Pthmax with HG, PImax or PEmax, r=0.550, p<0.05; r=0.583, p<0.001; and r=0.584, p<0.001, respectively). CONCLUSIONS: ExM endurance is decreased in patients with COPD. This impairment is proportional to the severity of the disease and is associated with lower strength in different muscle groups. This suggests that systemic effects are implicated in the impairment observed in ExM function.
The diagnostic accuracy of myeloperoxidase (MPO) in pleural fluid, for differentiating between complicated and noncomplicated parapneumonic pleural effusions (PPE) evaluated prospectively. Seventy patients aged >18 yrs with PPE (36 complicated and 34 noncomplicated) were studied after admission to a tertiary referral teaching hospital. MPO concentration was measured in plasma and pleural fluid using a double-antibody competitive radioimmunoassay. The concentrations of MPO in complicated and noncomplicated PPE were compared using a Mann-Whitney U-test and multiple logistic regression models were used to predict the odds that an effusion was complicated. MPO pleural-fluid concentrations were significantly higher in complicated than in noncomplicated PPE. After excluding purulent effusions, pleural-fluid MPO was the marker that best differentiated between the two types of PPE: the area under the receiver operating characteristic curve was 0.912, the sensitivity was 87.5% and the specificity was 85.1% at a cut-point limit of 3.000 microg x L(-1). The authors concluded that the concentration of pleural-fluid myeloperoxidase helps to differentiate between nonpurulent complicated and noncomplicated parapneumonic pleural effusions.
An ammonia process was applied at several ammonia loadings, moisture contents, temperatures, and dwell times. A cellulase loading of 5 FPU/g dry matter and a 24 h incubation time were used to produce the sugars, which were measured as reducing sugars and by HPLC. Optimal processing conditions caused a 76% of theoretical yield (2.9-fold above untreated). Cellulose and hemicellulose conversions were 68 and 85% (vs 38 and 34% in untreated, respectively). The short hydrolysis time and relatively low enzyme loading suggests great potential to produce sugars from alfalfa.
A warm-season legume, Florigraze rhizoma peanut (FRP), was used as the source of fiber to produce sugars. FRP was subjected to several ammonia-processing conditions using temperature, biomass moisture content, and ammonia loading as process variables during a 5-min treatment. A cellulase loading of 2 FPU/g DM and 24 h incubation were used to produce the sugars. Total sugar yield was 3.34-fold higher in the optimal treatment (1.5 g ammonia/g DM-60%-90 degrees C) compared to untreated and was 65.3% of theoretical. Cellulose and hemicellulose conversions increased from 30 and 15.5% in untreated FRP to 78 and 34% in treated FRP.
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BACKGROUND: The current study was conducted to analyze the outcome and prognostic factors of patients with diffuse large B-cell lymphoma (DLCL) who did not achieve a complete response (CR) to first-line treatment. METHODS: The current study was comprised of 83 patients (43 males and 40 females with a median age of 62 years) who did not achieve a CR (58 of whom had primary refractory disease and 25 of whom achieved a partial response) with initial treatment (doxorubicin-containing regimens in 87% of cases) from a series of 239 patients consecutively diagnosed with DLCL at a single institution. Initial variables, response to therapy, and salvage treatment were analyzed to predict survival. RESULTS: Compared with patients who achieved a CR, nonresponders or partial responders more frequently were of advanced age and had a poor performance status (PS), B-symptoms, advanced stage of disease, bone marrow infiltration, increased serum lactate dehydrogenase, and a high-risk International Prognostic Index. Among the 58 patients with primary refractory disease, 18 died during initial treatment due to toxicity (14 patients) or disease progression (4 patients). The main variables predicting early death were a poor PS, age > 60 years, and an immunoblastic DLCL subtype. Twenty-five of these 58 patients were able to receive salvage regimens, with only 1 of them achieving a CR. The median survival for this group of patients was 10 months. With regard to those patients achieving a partial response, 18 of the 25 patients received further therapy with 28% of them achieving a CR. The median survival was 23 months. The degree of the response was found to be the only significant variable with which to predict survival, with 2-year survival rates of 4% and 40%, respectively, for patients with primary refractory disease and patients who achieved a partial response. CONCLUSIONS: The prognosis of patients with primarily refractory DLCL is extremely unfavorable, whereas that of patients who achieve a partial response is slightly better. The inclusion of these patients in experimental trials is limited due to their tendency to be of an older age and to have a poor general status.
Patients with follicular lymphoma (FL) usually present with advanced disease, with lymph nodes and bone marrow involvement. Extranodal infiltration is infrequent. In FL isolated cutaneous relapse is a very rare event that, to the best of our knowledge, has not been previously reported. We report on a 55-year-old woman with FL who presented with an isolated skin relapse 5 years after the diagnosis. The patient, who had relapsed after three lines of chemotherapy, was treated with the chimeric anti-CD20 antibody, rituximab, achieving a complete response, which has now persisted for more than 24 months.
To evaluate expiratory muscle endurance in middle-aged healthy subjects using incremental as well as constant expiratory loads, 14 healthy volunteers (51 +/- 16 years) were submitted to a specific endurance test, which was performed breathing against a threshold valve, and was divided into two parts. In part I, the load was progressively increased (50 g each 2 min) until task failure occurred. The mean mouth pressure generated against the highest load held for at least 60 sec was defined as the maximal expiratory sustainable pressure (Pth(max)). In part II, each subject breathed against a constant submaximal expiratory load (80% Pth(max)) until task failure occurred (expiratory endurance time or Tth(80)). Both parts of the test were repeated 24-48 h later. Progressive expiratory loading induced a linear increase in mouth expiratory pressure and the Pth(max) obtained was 141 +/- 43 cm H(2)O, representing 74 +/- 28% of the maximal expiratory pressure (PE(max)). Under constant loads, the Tth(80) was 17 +/- 9 min. At the end-point of both parts, the tension time index for expiratory muscles was dramatically increased (>0.25), and both EMG central frequency and PE(max) were decreased with no changes in maximal inspiratory pressure or inspiratory capacity. Extreme dyspnea was present in most of the subjects but no complications were observed. The endurance of expiratory muscles can be easily assessed in healthy subjects using this method, which has acceptable reproducibility and tolerance.
Grape waste was composted by biodegradation and subsequently used as an organic fertilizer for 20 day-corn. Combinations of recently compressed grape waste and hen droppings (10% w/w) were prepared to study the activating effect of hen droppings and the effect of aeration on the composting process. The final hydrogen potential (pH), %C, %N and C/N ratio, indicated an adequate development of the bioprocess. Satisfactory results were observed when the products were applied at several doses (1,000-4,000 kg/ ha) as a soil conditioner for corn seed germination in greenhouses. Only the addition of hen droppings had a significant effect (P < 0.05) on corn dry matter (14% increase). A dose of 3000 kg/ha was considered as optimal and was used supplemented with triple superphosphate (TSP) in agronomic trials. All the treatments produced greater corn dry matter (P < 0.05) than the chemical industrial fertilizer used as a control (0.52-0.71 g/pot for the organic fertilizers vs 0.45 g/pot for the control). Anaerobic conditions and hen droppings addition significantly produced (P < 0.05) higher corn dry matter.
BACKGROUND: Aspergillus infection remains a major cause of morbidity and mortality after lung transplantation. Therefore, some strategies have been attempted, one of which is nebulized amphotericin B (nAB); however, the efficacy of this prophylaxis has not been shown clearly. The aim is to study whether nAB can protect against Aspergillus infection in lung transplant recipients. PATIENTS AND METHODS: A study of risk factors was conducted in 55 consecutive lung allograft recipients. Twenty-three potential risk factors were analyzed. In 44 (80%) patients, nAB was indicated as prophylaxis. Multivariate analysis using logistic regression was performed. RESULTS: Eighteen of the 55 patients (33%) developed infection due to Aspergillus spp. Multivariate analysis showed nAB to be a preventive factor (odds ratio: 0.13; 95% confidence interval [CI] 0.02-0.69; p < 0.05) and cytomegalovirus (CMV) disease was an independent risk factor for developing Aspergillus infection (odds ratio: 5.1; 95% CI 1.35-19.17; p < 0.05). Only 1 patient required withdrawal of the prophylaxis owing to bronchospasm. nAB was well-tolerated in the remaining patients with only a few, mild, easily controlled side effects. CONCLUSIONS: The present results show that nAB prophylaxis may be efficient and safe in preventing Aspergillus infection in lung-transplanted patients, and CMV disease increases the probability of Aspergillus infection.
Protein engineering is a promising tool to obtain stable proteins. Comparison between homologous thermophilic and mesophilic enzymes from a given structural family can reveal structural features responsible for the enhanced stability of thermophilic proteins. Structures from pig heart cytosolic and Thermus flavus malate dehydrogenases (cMDH, Tf MDH), two proteins showing a 55% sequence homology, were compared with the aim of increasing cMDH stability using features from the Thermus flavus enzyme. Three potential salt bridges from Tf MDH were selected on the basis of their location in the protein (surface R176-D200, inter-subunit E57-K168 and intrasubunit R149-E275) and implemented on cMDH using site-directed mutagenesis. Mutants containing E275 were not produced in any detectable amount, which shows that the energy penalty of introducing a charge imbalance in a region that was not exposed to solvent was too unfavourable to allow proper folding of the protein. The salt bridge R149-E275, if formed, would not enhance stability enough to overcome this effect. The remaining mutants were expressed and active and no differences from wild-type other than stability were found. Of the mutants assayed, Q57E/L168K led to a stability increase of 0.4 kcal/mol, as determined by either guanidinium chloride denaturalization or thermal inactivation experiments. This results in a 15 degrees C shift in the optimal temperature, thus confirming that the inter-subunit salt bridge initially present in the T.flavus enzyme was formed in the cMDH structure and that the extra energy obtained is transformed into an increase in protein stability. These results indicate that the use of structural features of thermophilic enzymes, revealed by a detailed comparison of three-dimensional structures, is a valid strategy to improve the stability of mesophilic malate dehydrogenases.
BACKGROUND: Pseudomonas aeruginosa is a frequent cause of infection in patients with bronchiectasis. Differentiation between non-infected patients and those with different degrees of P aeruginosa infection could influence the management and prognosis of these patients. The diagnostic usefulness of serum IgG antibodies against P aeruginosa outer membrane proteins was determined in patients with bronchiectasis without cystic fibrosis. METHODS: Fifty six patients were classified according to sputum culture into three groups: group A (n=18) with no P aeruginosa in any sample; group B (n=18) with P aeruginosa alternating with other microorganisms; and group C (n=20) with P aeruginosa in all sputum samples. Each patient had at least three sputum cultures in the 6 months prior to serum collection. Detection of antibodies was performed by Western blot and their presence against 20 protein bands (10-121 kd) was assessed. RESULTS: Antibodies to more than four bands in total or to five individual bands (36, 26, 22, 20 or 18 kd) differentiated group B from group A, while antibodies to a total of more than eight bands or to 10 individual bands (104, 69, 63, 56, 50, 44, 30, 25, 22, 13 kd) differentiated group C from group B. When discordant results between the total number of bands and the frequency of P aeruginosa isolation were obtained, the follow up of patients suggested that the former, in most cases, predicted chronic P aeruginosa colonisation. CONCLUSION: In patients with bronchiectasis the degree of P aeruginosa infection can be determined by the number and type of outer membrane protein bands indicating which serum antibodies are present.
In nonobese girls with an adolescent variant of polycystic ovary syndrome, insulin-sensitizing treatment reduces hyperinsulinism, dyslipidemia, and hyperandrogenism and restores eumenorrhea; however, the effect on anovulation is unknown. We assessed whether metformin treatment is capable of inducing ovulation in nonobese adolescents with anovulatory hyperandrogenism after precocious pubarche. The study population consisted of 18 adolescents (mean age, 16 yr; body mass index, 21.4 kg/m2; 3-7 yr beyond menarche) with hyperinsulinemic hyperandrogenism. All girls received metformin for 6 months in a daily dose of 1275 mg. Before inclusion, persistent anovulation was documented by weekly serum progesterone measurements less than 4 ng/ml (months -3 and -1); the ovulation rate was assessed similarly after 2, 4 and 6 months on metformin; a premenstrual progesterone level greater than 8 ng/ml was used as ovulation marker. Regular menses were reported by 16 of 18 girls within 4 months on metformin, and all girls were eumenorrheic after 6 months on metformin. Of the 18 girls, 1 (6%) ovulated after 2 months on metformin, 7 (39%) after 4 months, and 14 (78%) after 6 months; ovulation induction failed in the girls with the lowest birth weight or most severe hyperandrogenism. Metformin treatment was well tolerated. In conclusion, sensitization to insulin was found to be an effective approach to induce ovulation in nonobese adolescents with anovulatory hyperandrogenism.
Blastic natural killer (NK)-cell leukemia/lymphoma is a neoplasm of NK origin with aggressive behavior. The disease affects mainly elderly people and often presents with skin lesions and overt leukemia. Blastic morphology, an NK-cell immunophenotype, and lack of association with Epstein-Barr virus are the clues for the diagnosis. We report herein, the case of a patient with a blastic NK-cell leukemia/lymphoma with overt leukemia at diagnosis, who achieved a complete response after CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy. However, the patient relapsed a few months later and died due to disease progression. Cases of blastic NK-cell leukemia/ lymphoma previously reported are briefly reviewed.
This review focuses on the structural and functional changes occurring in respiratory as well as peripheral muscles in COPD patients. These changes are particular for each muscle territory or compartment. Respiratory muscles predominantly undergo structural adaptive changes. However, they have to do their job in unfavourable mechanical conditions and thus their function is impaired. Peripheral muscles have to be grouped in at least two different compartments: upper and lower limb muscles. The structure and function are relatively preserved in the former, due to the maintenance of some daily activities involving the arms or even the use of some of these muscles in the ventilatory effort. Lower limb muscles in contrast undergo involute structural changes which result in an impairment in their function and in the global exercise capacity of the individual. Deconditioning due to a reduction in daily activities secondary to ventilatory impairment is probably the driving factor for these changes. Although the level of activity appears to be the main determining factor in changes occurring in different territories, this would be modulated by other local and systemic factors, such as inflammation, oxidative stress, drugs and nutritional abnormalities.
The inhalation of wood dust may produce allergic rhinitis, asthma, or contact dermatitis in sensitized patients. We describe a patient with occupational asthma induced by the inhalation of samba (Triplochiton scleroxylon) wood dust. A specific bronchial provocation test was conducted, and the patient showed a significant decrease in forced-expiratory volume in first second (FEV1) after the inhalation of nebulized samba wood allergens. We suggest an IgE-mediated mechanism since the patient had a positive skin test and positive specific IgE determinations using an extract of samba wood. SDS-PAGE immunoblots revealed IgE binding to proteins with molecular weights of 17 kDa, 28 kDa and less intense binding to a band with an approximate molecular weight of 60 kDa. Two asymptomatic skin test-negative subjects, also occupationally exposed to samba, did not show any signs of bronchoconstriction when challenged with the samba wood extracts. We conclude that the occupational asthma suffered by this patient is related to sensitization and occupational exposure to samba wood dust.