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Biomedical subjects

J Alfaro

Publications and source records attributed to J Alfaro.

At least 19 recordsLinked to original sources
PubMed2005

Dendritic cell immunizations alone or combined with low doses of interleukin-2 induce specific immune responses in melanoma patients.

Dendritic cell (DC)-based therapy has proved to be effective in patients with a variety of malignancies. However, an optimal immunization protocol using DCs and the best means for delivering antigens has not yet been described. In this study, 20 patients with malignant melanoma in stages III or IV were vaccinated with autologous DCs pulsed with a melanoma cell lysate, alone (n = 13) or in combination with low doses of subcutaneous (s.c.) interleukin (IL)-2 injections (n = 7), to assess toxicity, immunological and clinical responses. Monocyte-derived DCs were morphological, phenotypic and functionally characterized in vitro. Peripheral blood mononuclear cells (PBMC), harvested from patients either prior to and after the treatment, were analysed using enzyme-linked immunosorbent spot (ELISPOT). After vaccination, 50% of the patients tested (seven of 13) from the first group and (three of seven) from the second, showed an increase in interferon (IFN)-gamma production in response to allogeneic melanoma cell lines but not to controls. Four of five tested human leucocyte antigen (HLA)-A2(+) patients with anti-melanoma activity also showed specific T cell responses against peptides derived from melanoma-associated antigens. Delayed type IV hypersensitivity reaction (DTH) against melanoma cell lysate was observed in six of 13 patients from the group treated with DC vaccines only and four of seven from the group treated with the combination of DCs and IL-2. Significant correlations were found between DTH-positive responses against tumour lysate and both disease stability and post-vaccination survival on the stage IV patients. There were no toxicities associated with the vaccines or evidence of autoimmunity including vitiligo. Furthermore, no significant enhancement was observed as a result of combining DC vaccination with IL-2. Our data suggest that autologous DCs pulsed with tumour lysate may provide a standardized and widely applicable source of melanoma specific antigens for clinical use. It is safe and causes no significant side effects and has been demonstrated to be partially efficient at triggering effective anti-melanoma immunity.

Antigen Presentation↗
PubMed2005

Attenuated response to purified protein derivative in patients with rheumatoid arthritis: study in a population with a high prevalence of tuberculosis.

BACKGROUND: The purified protein derivative (PPD) skin test is the only widely used method which detects latent tuberculosis infection (LTBI) and is dependent on a normal T cell function. In rheumatoid arthritis (RA) the T cell function is altered, which may result in an inability to develop an adequate PPD reaction. OBJECTIVES: To evaluate the response to PPD in patients with RA and to compare it with that of control subjects. METHODS: 112 patients with RA and 96 healthy controls were studied. PPD 5 U was applied using the Mantoux method, and skin reaction was measured at 72 hours. The reaction was considered negative for PPD <5 mm. RESULTS: There were no significant differences in age, sex, history of bacille Calmette-Guerin vaccination, or tuberculosis contact between the two groups. The median size of the PPD induration in the patients with RA was significantly less than that in the control group (4.5 v 11.5 mm, p<0.01). 79 (70.6%) patients with RA compared with 25 (26%) of the control group had a negative reaction to PPD (p<0.01), a response not influenced by disease activity or duration of disease in the patients with RA. CONCLUSION: A PPD skin test is not an appropriate test for recognising LTBI in patients with RA in our population.

Adult↗
PubMed2004

[Evaluation of a pharmaceutical care program to improve adherence to antiretroviral therapy].

OBJECTIVE: To establish the impact of a pharmaceutical care program on the improvement of adherence to antiretroviral therapy, and on patient immunologic and virologic outcome. MATERIALS AND METHODS: A multicenter, observational, prospective study in a HIV-infected patient cohort under treatment with antiretrovirals selected by random sampling in 19 Spanish hospitals. The study lasted 12 months, in which the program was applied through a baseline preprocedural visit and 4 quarterly visits. Adherence estimation was based on pill counting. An adherence > or = 90, or > or = 95% was considered adequate (in two time points). RESULTS: 541 patients were included, most of them were males (68.8%) between 20 and 78 years of age. Major risk groups included injecting drug users (43.4%) and heterosexuals (29.4%). Sixty percent had already received treatment for more than 3 years. Mean baseline viral load and CD4 count values were 32,866 copies/ml and 485 cells/mm3, respectively. Throughout the study a slight increase in the percentage of adherent patients was seen; however, statistical significance was not reached (64.3 and 79.2% of patients showed an adherence > 95 and > 90%, respectively, during the fourth quarter, versus 59.8 and 75.5% at baseline). A statistically significant decrease in viral load and increase in CD4 cells was seen following program application. The percentage of patients with a viral load < 200 copies/ml was 72.2, 76.7, and 75.0% at the 2nd, 3rd, and 4th quarters, respectively, versus 64.2% at baseline. CD4 cell counts increased by 50 cells/mm3 on average from the start to the end of follow-up. CONCLUSIONS: Patients included in the program had a good immunologic and virologic outcome, and a trend towards an increased percentage of patients with good adherence was also seen. These results confirm the need to implement follow-up programs for patients receiving antiretrovirals in order to ensure maximum therapeutic benefits.

Adult↗
PubMed2003

[The state of poisoning in Navarra].

We briefly comment on the state of clinical toxicology in Navarra and in the rest of Spain, with reference to the Toxicology Committee of Navarra and its aims. Epidemiological data from the Emergency Service of the Hospital of Navarra is presented, as well as where to find information on the subject; the epidemiological registration sheet designed by the SEMESTOX group is attached. A description is given of the characteristics of therapeutic drugs and drugs of abuse determination (type of sample, methodology and interpretation of results) carried out in the toxicological analytical unit of the Hospital of Navarra. Finally, reference is made to all of the antidotes available to the Pharmacy Service of the Hospital of Navarra, which is the reference center for the whole of the autonomous community of Navarra. A description is given for each medicine including its indications.

Humans↗
PubMed2001

Remediation of DNAPL pools using dense brine barrier strategies.

Although dense nonaqueous phase liquid (DNAPL) pools are an important source of groundwater contamination, little experimental data have been generated to develop a mature level of understanding of the problem, and few strategies specifically aimed at remediation have been advanced. We discuss the dominant importance of these features in subsurface systems, present novel two- and three-dimensional heterogeneous experimental systems, and show results from two evolving strategies for remediating DNAPL pools. These strategies involve the joint use of a dense brine barrier and controlled mobilization of trapped DNAPL using small-volume surfactant flushes. These experiments demonstrate a controlled, substantial reduction of entrapped DNAPL in both two- and three-dimensional heterogeneous domains, using less than a single pore volume of flushing solution in some cases.

Porosity↗
PubMed2001

The complete normalization of the adrenocortical function as the criterion of cure after transsphenoidal surgery for Cushing's disease.

Transsphenoidal microsurgery is the standard treatment for patients with Cushing's disease. However, there is general lack of agreement regarding the definition of cure. We studied 58 patients with corrected hypercortisolism after transsphenoidal surgery for Cushing's disease. Plasma and urinary cortisol levels were measured after surgery. After the postsurgical hypocortisolism stage (or periodically in patients without hypocortisolism), urinary free cortisol, plasma cortisol at 0800 h and 2300 h, morning cortisol after 1 mg dexamethasone, and cortisol response to insulin-induced hypoglycemia were performed. Patients were classified in 3 groups: group I, patients with transient hypocortisolism and normal hypothalamus-pituitary-adrenal axis afterwards; group II, patients with transient hypocortisolism and abnormalities in the circadian rhythm or the stress response afterwards; and group III, patients without postoperative hypocortisolism. Thirty-three patients were included in group I, 8 in group II, and 17 in group III. Groups I and II were similar in postsurgical plasma cortisol (46.9 +/- 30.3 vs. 60.7 +/- 38.6 nM) and mean follow-up (69.8 vs. 68.8 months) but were significantly different in their recurrence rate (3.4% vs. 50%, P < 0.001). Patients in group III had normal postsurgical plasma and urinary cortisol but persistent abnormalities in circadian rhythm and stress response. After a mean follow-up of 39.1 months, their recurrence rate was similar to that of group II (64.7% vs. 50%). The complete normalization of the adrenocortical function, which is always preceded by postsurgical hypocortisolism, is associated with a very low recurrence risk and should be considered, in our opinion, the main criterion of surgical cure in Cushing's disease.

Adrenal Cortex↗
PubMed2001

[Endoscopic coagulation with argon plasma, a therapeutic option in gastric antral vascular ectasia].

BACKGROUND: Gastric Antral Vascular Ectasia or Watermelon stomach is a rare cause of chronic gastrointestinal bleeding, often presenting as a chronic iron deficiency anemia. This condition can be associated with some other diseases such as cirrhosis, autoimmune diseases and others. We report two patients treated with Argon Plasma Coagulation, a 68 years old male with an ethanol related cirrhosis and a 72 years old female with an idiopathic Gastric Antral Vascular Ectasia. The characteristic endoscopic features were mistaken for many years as gastritis. Both patients presented with severe anemia requiring multiple transfusions as treatment. Due to the poor operative risk, both patients were treated with Argon Plasma Coagulation with good results.

Aged↗
PubMed2000

Quantum gravity corrections to neutrino propagation

Massive spin-1/2 fields are studied in the framework of loop quantum gravity by considering a state approximating, at a length scale L much greater than Planck length l(P), a spin-1/2 field in flat spacetime. The discrete structure of spacetime at l(P) yields corrections to the field propagation at scale L. Neutrino bursts ( &pmacr; approximately 10(5) GeV) accompanying gamma ray bursts that have traveled cosmological distances L are considered. The dominant correction is helicity independent and leads to a time delay of order (&pmacr;l(P))L/c approximately 10(4) s. To next order in &pmacr;l(P), the correction has the form of the Gambini and Pullin effect for photons. A dependence L(-1)(os) approximately &pmacr;(2)l(P) is found for a two-flavor neutrino oscillation length.

Journal Article↗
PubMed2000

[Acute poisoning with methotrexate used as an abortifacient: description of 2 cases].

Acute intoxication with methotrexate, used as an abortive, has not been described in Chile. We report two female patients, aged 15 and 24 years old, who presented with mucositis, erythrodermia, pancytopenia, and elevation of hepatic enzymes. Plasma methotrexate levels confirmed the clinical diagnosis and both patients were treated with high leucovorin doses and management of associated complications. In one patient, pregnancy continued, giving birth to a newborn with cranial, face and limb malformations. The second patient had a late rescue with leucovorin and was discharged with a persistent sensory motor neuropathy. Considering the severity of complications and that patients may deny its use, when there is reasonable clinical suspicion of methotrexate intoxication, leucovorin treatment should be started.

Abortifacient Agents, Nonsteroidal↗
PubMed1998

Colorectal cancer: morphologic variables related with carcinoembryonic antigen serum elevation (CEA).

OBJECTIVE: The purpose of this study is to identify morphologic parameters of colorectal adenocarcinoma which may be of influence in the increase of preoperatory CEA serum levels. METHOD: This study includes 127 patients on whom colectomy was performed. Twenty-eight morphologic parameters were analyzed in each surgical specimen. Serum determinations were made by enzymatic immunoassay. A multivariate study (logistic regression analysis) was made. Independent risk factors for CEA serum elevation were Cytologic Atypia (odd ratio: 2.85) Infiltrative Growth Pattern (odd ratio: 2.91) and the presence of tumoral cell infiltration directly among adipocytes (odd ratio: 2.62). When clinical variables (age, sex, tumor location, perforation, occlusion, hepatic metastases and peritoneal carcinomatosis) were added the infiltrative growth pattern (odd ratio: 3.12) and cytologic atypia persisted as independent risk factors, together with the clinical variable Hepatic Metastases (odd ratio: 24.84). CONCLUSION: In our series the morphologic variables Infiltrative Growth Pattern and Cytologic Atypia are independently related with CEA serum increase and are not influenced by the variable Hepatic Metastases.

Adult↗
PubMed1997

Foster care: an update.

OBJECTIVE: To inform child and adolescent psychiatrists about the almost 500,000 children now residing in the American foster care system. This overview surveys the pediatric, developmental, and psychiatric needs of these children. METHOD: Child and adolescent psychiatrists, pediatricians, a child welfare researcher, a social worker, and a psychologist developed a consensus paper from their experience with child welfare and a review of the literature in their respective fields. RESULTS: Being in foster care is a defining experience in these children's lives. They are at risk in myriad ways: for instance, being poor, having chronic health deficits, experiencing the trauma of abuse and neglect, and suffering from a gamut of emotional challenges. Evolutionary developments in foster care such as therapeutic foster homes, kinship care, and changes in Medicaid funding will continue to alter the system. CONCLUSIONS: Foster children are a huge reservoir of unmet pediatric and psychiatric needs; research on them is spotty at best. It is hoped that child and adolescent psychiatrists will meet the challenges these youngsters present and will advocate for them.

Adolescent↗
PubMed1995

Platelet autoantibodies in patients with chronic liver disease.

The thrombocytopenia in chronic liver disease (CLD) has been attributed mainly to hypersplenism, although other factors such as reduced mean life span with increased platelet turnover have also been demonstrated. Immunological abnormalities have been described in the pathogenesis and progression of CLD. In this sense, many studies have reported elevated levels of platelet associated IgG (PAIgG) in patients with CLD, and it has been suggested that PAIgG could represent true antiplatelet antibody. In this study we used a glycoprotein (GP)-specific immunoassay (MACE) to determine whether PAIgG or circulating antiplatelet antibodies, reacted against the GPIIb/IIIa or GPIb/IX complexes, in patients with CLD. Thirty-six patients with CLD of diverse etiology were studied (20 female, mean age 53 years, range 38-75 years). 23 out of 36 patients (64%) had anti-GP antibodies in MACE. Particularly, 12 had anti-GPIb, 4 anti-GPIIb/IIIa, and 7 had both types of autoantibodies. The existence of these anti-GP antibodies was not related with the blood platelet count or etiology of CLD. These data show that in patients with CLD of diverse origin, there is a high prevalence of autoantibodies reacting specifically with platelet membrane GP, which constitutes the first evidence of the specific nature of platelet-bound IgG in CLD. These findings suggest that in patients with CLD, an immune mechanism may participate in inducing or aggravating the thrombocytopenia.

Adult↗
PubMed1995

Antimetastatic effect of immunization with liposome-encapsulated tumor cell-membrane proteins obtained from experimental tumors.

Immunization of C57BL/6 mice with tumor-derived membrane-proteins encapsulated in sized liposomes (0.2 microgram/mouse) and composed by phosphatidylcholine or sphingomyelin, significantly reduced the mean values of spontaneous lung metastasis from both B16 (0.7 +/- 0.5 and 1.2 +/- 0.6, respectively) and 3LL (4.8 +/- 2.5 and 7.2 +/- 4.1, respectively) tumors, with respect to control (HEPES) groups (4.8 +/- 1.1 and 19.0 +/- 4.4, respectively). However, no significant antimetastatic effect was observed using free tumor-derived proteins (2 micrograms/mouse) or liposome vehicle alone. Specific humoral immune response after the vaccination was studied by flow cytometry of tumor cells incubated with a pooled sample from each group of immunized mice and FITC-conjugate antimouse immunoglobulins. The results showed that the highest number of positive tumor cells was identified using sera from immunized mice with sized liposomes encapsulating tumor-derived proteins whereas the immunization with the protein fraction in free form failed to induce this effect. In addition, an increased cytotoxicity towards 3LL and B16 tumor cells can also be observed when tumor cells were incubated with spleen effector cells plus specific immunosera. In conclusion, our results show that antitumor active vaccination, using sized liposomes as adjuvants, induces an antitumor host response and a significant inhibition of tumor progression.

Animals↗
PubMed1994

[A case of neutropenia and agranulocytosis induced by clozapine. The importance of a drug surveillance program for their early detection].

Clozapine is an atypical antipsychotic drug with a very low incidence of extrapyramidal effects, used in the treatment of schizophrenic patients refractory or intolerant to classical neuroleptics. Its use is limited due to the potential risk of producing agranulocytosis in 1 to 2% of patients. Despite the severity of this complication, the Federal Drug Administration allowed its use as long as its prescription is associated to a drug surveillance program that controls regularly the white cell count of patients using the drug. Three hundred three patients (210 male) have been admitted to a clozapine drug surveillance program. Two patients had a transitory leukopenia with less than 2000 leukocytes/ml and less than 1000 neutrophyls/ml, that reverted after discontinuing the drug. One patient, whose case is described, had a severe agranulocytosis with less than 500 neutrophyls/ml that required hospital admission.

Adult↗