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P Delgado

Publications and source records attributed to P Delgado.

At least 37 records · Page 2Linked to original sources
PubMed1999

Antidepressants and the brain.

The pathophysiology and effects of antidepressants in the brain are still poorly understood. While it is generally accepted that increasing the levels of monoamine in the brain is an effective way to alleviate depression, the precise neurobiological mechanisms are unclear. The evidence that monoamine function is impaired in individuals with depression is largely indirect. However, the neurotransmitter depletion model allows a more direct investigation of the role of the monoamines. In this model, tryptophan depletion is used to lower levels of serotonin and alpha-methylparatyrosine is used to induce catecholamine depletion in the brain. Studies have shown that such depletion transiently reverses antidepressant responses in the majority of patients, the response being dependent on the type of antidepressant used. However, depletion in unmedicated patients with depression did not worsen the depressive symptoms, neither did it cause depression in healthy subjects with no history of mental illness. The cause(s) of depression therefore appears to be more complex than simply a reduction in levels of monoamine or diminished function in these systems. The pathophysiology of depression may relate to dysfunction in brain areas modulated by monoamine systems. Antidepressant drugs may mediate their effects by causing adaptive changes in neurones localised in these brain areas.

Animals↗
PubMed1999

[ Magnetic resonance imaging in the early diagnosis of bone marrow necrosis].

Bone marrow necrosis (BMN) is a rare entity characterised by fever and bone pain, accompanied by hypercalcemia and increased LDH. Amorphous eosinophilic material is present in the bone marrow aspirate, with isolated cells in different degrees of necrobiosis. These are frequently post-mortem findings, appearing in up to 19.8% of all autopsies, mostly after haematological malignancies with proliferative features (acute leukaemia, lymphoma). In general terms, BMN is regarded as a poor prognosis sign. Bone gammography with Tc has been included among the diagnostic procedures, in an attempt to carry out an early detection of BMN and to determine its spread. Magnetic resonance imaging (MRI) has recently been regarded useful to evaluate bone marrow involvement in this condition. A 53 year-old woman is presented here who, two and a half years after being diagnosed of mantle cell lymphoma, and having a relapse on her neck lymph nodes, presented severe bone pain showing no radiological evidence of osseous involvement. MRI showed ample spongy marrow involvement of her lower spine, sacrum and pelvic bones. Both femoral heads were preserved, hypointense images being observed in T1, whereas subcortical, hyperintense ones appeared in T2. Bone marrow aspirate showed poor cellularity, with different degrees of necrobiosis on a stippled background. The picture was interpreted as BMN secondary to non-Hodgkin's lymphoma.

Bone Marrow↗
PubMed1999

High population differentiation and genetic variation in the endangered Mexican pine Pinus Rzedowskii (Pinaceae).

Pinus rzedowskii is an endangered pine species from Michoacán (central México), which has been previously reported from only three localities. Classified within the subgenus Strobus, it exhibits intermediate morphological characters between subgenera Strobus and Pinus. We analyzed genetic aspects that could shed light on the evolution and conservation of this species. The genetic structure of nine populations was examined using 14 isozyme loci. Pinus rzedowskii has a relatively high level of genetic variation with 46.8% of the loci assayed being polymorphic, a total of 35 alleles, and a mean heterozygosity per population of 0.219. We calculated Wright's F(ST) statistic to estimate gene flow indirectly and to evaluate whether or not there was genetic structuring among populations. We found a marked differentiation among populations (F(ST) = 0.175) and significant inbreeding (F(IS) = 0.247). No pattern of isolation by distance was found. We also constructed a dendrogram based on a genetic distance matrix to obtain an overview of the possible historical relationships among populations. Finally, we found a convex relationship between the genetic distance among populations and the number of ancestral lineages, suggesting that demographically this species has not been at risk recently. Although endangered, with small and fragmented populations, P. rzedowskii shows higher levels of genetic variation than other conifer species with larger populations or similar conservation status.

Journal Article↗
PubMed1998

CD26 expression and dipeptidyl peptidase IV activity in an aggressive hepatosplenic T-cell lymphoma.

The transmembrane serine aminopeptidase dipeptidyl peptidase IV (DPP IV) (also known as CD26) participates in several immunological functions and has a binding affinity for several molecules, including collagen, which may be an integral mechanism for T cells to traverse endothelial barriers. Since CD26 is phenotypically expressed in certain T-cell malignancies, this study utilized a novel four-color cytofluorographic procedure to measure DPP IV enzymatic activity concurrently with the expression of other surface markers in an aggressive hepatosplenic T-cell lymphoma. Immunophenotypic analysis by flow cytometry revealed the tumor to be CD2+, CD3+, CD5-, CD7+, TcR-gamma/delta+, CD4-, CD8+/-, CD56+, and CD11c+. The CD26 molecule was also expressed, and DPP IV activity was present, with the maximal activity detectable after 10 min of incubation. These results represent the initial description of enzymatically active CD26 in a T-cell malignancy, and raise the possibility that this molecule may be a participant in the pathogenetic mechanisms utilized by the neoplastic cells.

Adolescent↗
PubMed1998

Structural analysis of inhibitor binding to human carbonic anhydrase II.

X-ray crystal structures of carbonic anhydrase II (CAII) complexed with sulfonamide inhibitors illuminate the structural determinants of high affinity binding in the nanomolar regime. The primary binding interaction is the coordination of a primary sulfonamide group to the active site zinc ion. Secondary interactions fine-tune tight binding in regions of the active site cavity >5 A away from zinc, and this work highlights three such features: (1) advantageous conformational restraints of a bicyclic thienothiazene-6-sulfonamide-1,1-dioxide inhibitor skeleton in comparison with a monocyclic 2,5-thiophenedisulfonamide skeleton; (2) optimal substituents attached to a secondary sulfonamide group targeted to interact with hydrophobic patches defined by Phe131, Leu198, and Pro202; and (3) optimal stereochemistry and configuration at the C-4 position of bicyclic thienothiazene-6-sulfonamides; the C-4 substituent can interact with His64, the catalytic proton shuttle. Structure-activity relationships rationalize affinity trends observed during the development of brinzolamide (Azopt), the newest carbonic anhydrase inhibitor approved for the treatment of glaucoma.

Binding Sites↗
PubMed1997

Treatment of the male with follicle-stimulating hormone in intrauterine insemination with husband's spermatozoa: a randomized study.

We have examined the potential of follicle-stimulating hormone (FSH) therapy for the male to improve pregnancy rates in intrauterine insemination (IUI) with husband's spermatozoa. A prospective randomized trial was performed in 148 couples undergoing IUI because of male subfertility. In the treatment group, 150 IU FSH were administered to the husbands, either i.m. or s.c., three times a week, starting 3 months before the beginning of IUI cycles and maintained until the fifth IUI cycle. In the control group no treatment was given. FSH therapy did not change semen parameters. The pregnancy rate per cycle was 13.47% in the FSH group versus 10.07% in the non-FSH group; the pregnancy rate per woman was 44.38% in the FSH group versus 37.18% in the non-FSH group. Although the pregnancy rate increase was > 30% per cycle and > 20% per woman, statistical significance was not achieved. The cumulative pregnancy rate was 59.20% in the FSH group versus 42.91% in the non-FSH group. The pregnancy rate outside the IUI cycle was 14.70% (10/68) in the FSH group versus 2.5% (2/80) in the non-FSH group, the difference being statistically significant. In conclusion, a non-significant trend towards higher pregnancy rates in IUI was observed in the FSH group.

Female↗
PubMed1996

Diagnostic discrimination and cost effective assay strategy for leukocyte alkaline phosphatase.

Decreased leukocyte alkaline phosphatase (LAP) is a first line test for chronic myelogenous leukemia (CML), generally preceding a diagnostic algorithm which also includes bone marrow biopsy, cytogenetic analysis, and molecular diagnostics. We found the analytical uncertainty of LAP assays to range from over 100% coefficient of variation at low scores to about 20% at high scores. However, the receiver-operator characteristics derived from LAP determinations in 50 consecutive cases suggest that a suitably high diagnostic decision threshold still can eliminate false negatives. As a consequence of such a strategy, as many as half the tested patients, classified unequivocally as the negatives, can avoid further invasive and costly workup. On the other hand, serial LAP determinations, whether performed to detect change to a lower or to a higher score, are unlikely to produce conclusive diagnostic signals exceeding analytical 'noise.'

Alkaline Phosphatase↗
PubMed1996

[Disseminated zygomycosis by Absidia corymbifera in 2 leukemic patients].

AIM: The term zygomycosis comprise mycotic infections produced by mucorales and entomophtorales. Mucorales become pathogenic in some conditions, principally diabetes mellitus, immunosuppression, trauma or burn. METHODS: We describe two cases of leukaemic patients who developed disseminated zygomycosis by Absidia corymbifera during the aplastic phase by antineoplastic chemotherapy. RESULTS: In both cases, the first symptom was high fever unresponsive to broad spectrum antibiotics neither fluconazole. Initial sites of infection were sinonasal region in one case and bowel in the other one. The diagnosis was confirmed by culture of nasal swab and peritoneal fluid respectively. One patient was early diagnosed and he received prolonged amphotericin B therapy but no surgical debridement. The other one had a postmortem diagnosis at autopsy. None of them survived. Death was directly related to the fungal infection. CONCLUSIONS: Although this infection is infrequent, it must be suspected in high-risk patients because early diagnosis and quick combined therapy appear to improve the prognosis.

Child, Preschool↗
PubMed1994

Isolation and characterization of libraries of monoclonal antibodies directed against various forms of tubulin in Paramecium.

Ciliates are very good models for studying post-translationally generated tubulin heterogeneity because they exhibit highly differentiated microtubular networks in combination with reduced genetic diversity. We have approached the analysis of tubulin heterogeneity in Paramecium through extensive isolation and characterization of monoclonal antibodies using various antigens and several immunization protocols. Eight monoclonal antibodies and 10 hybridoma supernatants were characterized by: i) immunoblotting on ciliate and pig brain tubulins as well as on peptide maps of Paramecium axonemal tubulin; ii) immunoblotting on ciliate tubulin fusion peptides generated in E coli, a procedure which allows in principle to discriminate antibodies that are directed against tubulin sequence (reactive on fusion peptides) from those directed against a post-translational epitope (non-reactive); and iii) immunofluorescence on Paramecium, 3T3 and PtK2 cells. Twelve antibodies labeled all microtubules in Paramecium cells and were found to be directed against tubulin primary sequences (nine of them being located in the alpha N-terminal domain, one in the beta C-terminal one, and two in alpha and beta central stretches). The remaining ones decorated only a specific subset of microtubules within the cell and were presumably directed against post-translational modifications. Among these, three antibodies are directed against an N-terminal acetylated epitope of alpha-tubulin whereas the epitopes of three other ones (TAP 952 degrees, AXO 58 and AXO 49 degrees) apparently correspond to still unidentified post-translational modifications, located in the C-terminal domain of both alpha- and beta-tubulins. The AXO 49 degrees specificity is similar to that of a previously described polyclonal serum raised against Paramecium axonemal tubulin [2]. The results are discussed in terms of identification and accessibility of the epitopes and immunogenicity of ciliate tubulin with reference to mammalian and ciliate tubulin sequences.

Amino Acid Sequence↗
PubMed1994

Inhibition of presynaptic catecholamine synthesis with alpha-methyl-para-tyrosine attenuates nocturnal melatonin secretion in humans.

The catecholamine dopamine (D) is involved in the regulation of LH and PRL secretion, whereas a dysregulated noradrenergic system may contribute significantly to symptoms encountered in affective disorders. This explains the attraction of using alpha-methyl-para-tyrosine (AMPT) in neuroendocrine and psychiatric research, as it inhibits both neurotransmitters. PRL has been used as a marker of the effectiveness of AMPT in blocking D function, but no good marker for the effectiveness of AMPT in blocking norepinephrine (NE) is available. The purpose of this study was to determine whether melatonin (M) might serve as such a marker, as its production and secretion are regulated by NE. Seven subjects were given either AMPT or promethazine, which does not alter M secretion, in a randomized, double blind fashion, and 24-h M secretion was studied. Two-way analysis of variance revealed a significant difference in M secretion (F = 13.2; df = 17,102; P = 0.0013), with the following time points being different: 22, 23, 24, 1, 2, 3, 4, 5, and 6 h. Also, 24-h urinary 6-sulfatoxymelatonin excretion correlated highly with 24-h M secretion, expressed as the area under the curve in the AMPT experiment (r = 0.93; P = 0.002), which indicates that AMPT does not alter the metabolism of M. These results demonstrate for the first time that AMPT significantly attenuates nocturnal M secretion. It is concluded that M is a good marker for characterizing the effectiveness of AMPT in inhibiting sympathetic NE activity.

Adult↗
PubMed1994

[Incidence, clinico-biological characteristics, and clinical course of 1,203 monoclonal gammopathies (1971-1992)].

PURPOSE: To evaluate the incidence of monoclonal gammopathies (MG) in our sanitary district, to determine the associated diseases, and to analyse their clinical course along a period of over 20 years. PATIENTS AND METHODS: The study comprised 1,203 patients with MG, of whom 397 had multiple myeloma (MM) and 806 had non-myelomatous monoclonal gammopathies (NMMG). All patients were diagnosed and followed in the Department of Haematology of the Miguel Servet Hospital, in Zaragoza, between january 1971 and december 1992. The SWOG criteria for MM and those proposed by Kyle for NMMG were followed in all cases. The explorations performed in every patient included physical examination, x-ray skeletal survey, peripheral blood study, bone-marrow aspiration or biopsy, study of liver and kidney function. The protein study carried out in blood and urine included agarose gel electrophoresis and electroimmunofixation. Descriptive statistics and determination of actuarial accumulated risk for the transformation of MG undetermined significance (MGUS) into malignant MG (MMG) were also carried out. RESULTS: Incidence: The yearly incidence of MG remained stable up to 1985 as 25 new cases; from that time on, a 30-40% yearly increase was noticed, this increase being mainly related with NMMG. Distribution: MM included 397 patients (33.0%), while 806 cases (67.0%) had NMMG. In these last were included those MG associated to haematologic malignancies, 139 cases (11.5%) or to other diseases, 286 cases (23.8%), as well as MGUS, 347 cases (28.9%), and in 34 cases the MG acquired a transient character. The mean age in the series was 62.1 years, ranging between 2 and 92, and the M/F ratio was 1.13. IgG was the commonest immunochemical type, 762 cases (63.3%), followed by IgA, 214 cases (17.8%) and IgM, 114 cases (9.5%) Multiple MG appeared in 3.8% of the cases, 64 instances, with monoclonal component present only in urine. Of the MG associated to blood diseases, the highest frequency corresponded to lymphoproliferative disorders (74.8%), and of those MG associated to other disease, neoplasms and liver diseases were the commonest. The second place in frequency corresponded to MGUS, in which a periodical follow-up with median duration of 37.8 months was kept in 93.6% of the cases. Ten patients evolved into MMG within a median of 60 months, having an actuarial accumulated risk of 4.5%, 15% and 26% at 5, 10 and 15 years, respectively. CONCLUSIONS: (1) MG are relatively frequent disorders, representing an important number of interventions for a general haematology department each year. (2) MM is the commonest of all MG, followed by MGUS. (3) The clinical importance of MM lies upon the possibility of evolving into MMG. In this series, ten patients developed MMG within a median of 60 months and having an actuarial risk of 4.5%, 15% and 26%, respectively, at 5, 10 and 15 years.

Female↗
PubMed1994

[Transient monoclonal gammopathies. Study of 34 cases].

PURPOSE: To evaluate the incidence of transitory monoclonal gammopathies (MG) defined as a narrow spike in serum electrophoresis disappearing after a variable period of time. MATERIAL AND METHODS: A follow up (1986-1992) in all the cases with "minimal" MG (< 10 g/L) to evaluate the transitory or permanent nature of the patients sera was performed along a 7-year period. Serum protein electrophoresis along with immunofixation electrophoresis were performed in order to identify and characterize the monoclonal components in all the cases. RESULTS: Thirty four out of 592 monoclonal gammopathies (5.7% of the total and 8.6% of the non-myelomatous monoclonal components) fulfilled the criteria of transitory monoclonal gammopathies. There was predominance of adult patients (88.2%), females (64.7%) and subjects over 40 years of age (67.6%). The monoclonal component was small in all the cases (mean 4.5 g/L). After immunochemical characterization, IgG was found in 23 cases and IgM in 9; the light chain was Kappa in 25 and lambda in 7; two patients had 2 or 3 monoclonal components. In 31 of the 34 cases the associated pathology was infectious; this being neoplastic in 2 and hypersensitivity to drugs in the remaining patient. The infectious agents could be identified in 24 instances as mainly gram-negative bacteria. CONCLUSIONS: 1) The appearance of a transitory monoclonal gammopathy is not an unusual finding. 2) This alteration does not have any prognostic significance. 3) The appearance of a small monoclonal component, especially in infectious diseases, should not elicit deeper studies.

Adolescent↗
PubMed1993

Aortic dissection due to discontinuation of beta-blocker therapy.

beta-Blockers are known to protect a vulnerable aorta from acute dissection, as well as reducing the risk of recurrent dissection. This case presentation reports the history of a 60-year-old male suffering from acute aortic dissection following discontinuation of beta-blocker therapy. The patient has shown arterial hypertension for about 20 years treated solely by beta-blockers. Two days after stopping the use of metoprolol, a nonselective beta 1-blocker without ISA, the patient developed severe chest pain during exercise. Diagnosis of type I-aortic dissection according to DeBakey was achieved by transthoracal echocardiography and computed tomography. Successful surgery by replacement of the ascending aorta was performed about 1 h following admission to the intensive care unit. During the procedure, tamponade of the left ventricle occurred followed by cardiogenic shock. Postoperative management was complicated by prolonged respiratory therapy and acute gastrointestinal bleeding; 1-year follow-up showed no evidence of disease. Thus, in this case acute dissection may be the consequence of discontinuing the use of metoprolol, possibly due to uncontrolled hypertension or specific response to the beta-blocker.

Aortic Dissection↗
PubMed1993

Blood cardioplegia with warm reperfusion versus intermittent aortic crossclamping in myocardial revascularization. Randomized controlled trial.

To compare the efficiency of two methods of myocardial protection--blood cardioplegia and warm reperfusion with aspartate-glutamate enrichment of the solution versus intermittent aortic crossclamping--we randomized 60 patients for coronary artery bypass grafting. Hemodynamic parameters and hospital mortality were the end points. Pathologic antecedents and preoperative clinical conditions were similar in both group I (blood cardioplegia, 30 patients) and group II (aortic crossclamping, 30 patients). An average of 2.9 grafts per patient were performed in group I and 3.1 in group II. Duration of extracorporeal circulation was 100 +/- 28 minutes in group I and 85 +/- 23 minutes in group II (p < 0.05). The total time of aortic crossclamping was 62.8 +/- 24.5 minutes in group I and 44.3 +/- 14.9 minutes in group II (p < 0.05). There were comparable increases in cardiac index in group I and group II from the preoperative period to the first postoperative day, but none of these changes reached statistical significance. There were two deaths, one in the cardioplegia group (3.3%) and another in the intermittent aortic crossclamping group (3.3%). In conclusion, in myocardial revascularization, intermittent aortic crossclamping and blood cardioplegia with warm reperfusion enriched with aspartate-glutamate solution are methods of similar efficiency.

Aorta↗