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Biomedical subjects

A Domingo

Publications and source records attributed to A Domingo.

At least 19 recordsLinked to original sources
PubMed2003

Richter's syndrome after allogeneic stem cell transplantation for chronic lymphocytic leukaemia successfully treated by withdrawal of immunosuppression, and donor lymphocyte infusion.

Development of high-grade non-Hodgkin's lymphoma is a possible complication of chronic lymphocytic leukaemia/small lymphocytic lymphoma, known as Richter's syndrome (RS). Treatment for RS includes systemic chemotherapy and, recently, allogeneic stem cell transplantation (SCT). We describe a patient with B-chronic lymphocytic leukaemia who developed RS 4 months after allogeneic SCT from an HLA-identical sibling. The RS presented with systemic symptoms, lymphadenopathy, pancytopenia and serum lactate dehydrogenase elevation. The patient was treated with immunosuppressive drug withdrawal and a donor lymphocyte infusion (DLI) of 1 x 10(7) CD3/kg, leading to the disappearance of all symptoms and the attainment of complete donor chimerism. After 18 months of the therapeutic DLI, the patient continues in complete remission.

Erythrocytes↗
PubMed2003

Sézary syndrome and related variants of classic cutaneous T-cell lymphoma. A descriptive and prognostic clinicopathologic study of 29 cases.

Large series of patients with Sézary syndrome (SS), the leukemic variant of cutaneous T-cell lymphoma (CTCL), have been reported infrequently because of its low incidence. Here we recorded several clinical, histopathological and immunophenotypical features of 29 cases of leukemic CTCL patients from four Dermatology Departments of Catalonia, Spain, and analyzed their prognostic value. Clinical data included sex, age, delay of SS diagnosis, previous diagnosis of lymphoma, B-symptoms, type of skin lesions, peripheral adenopathy, histologic evaluation of lymph node biopsy, visceral involvement, percentage of circulating Sézary cells, serum LDH and beta-2-microglobulin levels, first treatment and response, disease-free interval, further therapies and survival. Histopathological data examined were epidermotropism, depth and thickness of the infiltrate, cell size, adnexal involvement, presence of granuloma, eosinophils and plasma cells, mitotic rate. The percentage of CD45Ro, CD43, CD20, CD30 and CD8 positive dermal cells were also recorded. Survival showed a mean actuarial risk of 57% at 3 years and 38% at 5 years, with a median survival of 48 months. Analysis of actuarial survival demonstrated as following as features linked with a bad prognosis: fast evolution of the disease (from symptoms onset up to diagnosis) (p = 0.0274) raised levels of serum lactate dehydrogenase (p = 0.0379) and beta-2-microglobulin (p = 0.0151), the latter being the most important prognostic factor. In conclusion although SS had been traditionally considered as a low-grade lymphoma, the present study agrees with the recent classification rating SS as an aggressive type of CTCL with a poor prognosis. Our results show that some simple clinical and blood test data can be useful as prognostic indicators in this disease.

Adult↗
PubMed2001

Interferon alpha and zidovudine therapy in adult T-cell leukaemia lymphoma: response and outcome in 15 patients.

Adult T-cell leukaemia lymphoma (ATLL) is an aggressive disease caused by the human T-lymphotropic virus 1 (HTLV-I) with a short survival. Responses to interferon alpha (IFN-alpha) and zidovudine (AZT) have been documented but not with long-term follow-up. We treated 15 ATLL patients with IFN and AZT. Eleven patients had acute ATLL, two had lymphoma and two smouldering ATLL, with progression. The main features were: organomegaly (14), skin lesions (10), high white blood cell (WBC) count (11) and hypercalcaemia (9). Eleven patients had previously received chemotherapy and one had received an autograft. At the time of the study, seven patients had progressive disease and eight were in partial or complete clinical remission. Responses (PR) lasting 2+ to 44+ months were seen in 67%; 26% did not respond (NR) and one patient was not evaluable. Hypercalcaemia predicted a poor outcome but differences were not significant. Eight of the 15 patients have died 3-41 months from diagnosis. Median survival for the 15 patients was 18 months. Survival of the NR ranged from 4 to 20 months; six PR patients are alive 8-82 months from diagnosis. The differences in survival between NR (median: 6 months) and PR (55% of patients alive at 4 years) were statistically significant (P = 0.002). In conclusion, IFN and AZT improves the outcome of ATLL patients and helps maintain responses.

Adult↗
PubMed2001

Epidermal growth factor increases surface hydrophobicity and resistance to acid in the rat duodenum.

Epidermal growth factor (EGF) is produced in Brunner's glands and plays a role in healing and repair of duodenal ulcers. We examined the participation of zwitterionic phospholipids of mucus in the effects of EGF. Under anesthesia, groups of rats received an intraduodenal bolus of either saline or EGF. Some rats received subcutaneous indomethacin followed by EGF or EGF followed by a detergent (5% Brij 35, a nonionic detergent that solubilizes luminal phospholipids). Thirty minutes after treatment, mucosal surface hydrophobicity and phospholipid concentration in the mucus layer were measured. Matched groups of rats were challenged with 0.5 M HCl, instilled intraduodenally 30 min after treatment, and mucosal damage was assessed 1 h after acid challenge. Exogenous EGF significantly increased surface hydrophobicity and phosphatidylcholine concentration in the mucus layer. EGF treatment also reduced mucosal damage induced by acid. However, indomethacin pretreatment or detergent administration after EGF abolished both protection against acid and changes in the mucus layer. These data suggest that EGF increases duodenal resistance to luminal acid via stimulation of mucosal zwitterionic phospholipids.

Animals↗
PubMed2001

Usefulness and reproducibility of cytomorphologic evaluations to differentiate myeloma from monoclonal gammopathies of unknown significance.

We attempted to differentiate monoclonal gammopathies of unknown significance (MGUS) and multiple myeloma (MM) on morphologic grounds and to determine interobserver reproducibility of the differentiation. Cytologists blindly evaluated bone marrow smears from 154 patients with bone marrow plasmacytosis for the proportion of plasma cells with predefined cellular atypias. The single morphologic characteristic that most strongly differentiated MM from MGUS was the presence of nucleoli. The percentage of plasma cells, cytoplasmic contour irregularities, and anisocytosis also predicted a diagnosis of myeloma in multivariate analysis. Six cytologists independently evaluated 68 consecutive cases to determine sensitivity and specificity of these cytomorphologic features. The interobserver coefficient of variation for the plasma cell count was 33%. On consideration of the diagnosis, 36 of 41 MGUS cases and all 24 cases of myeloma were classified correctly. The use of a predesigned score system did not present such a bias, although it did not improve overall efficiency. The plasma cell count is the most predictive characteristic of myeloma from a cytologic viewpoint, but the interobserver variability is high. Interobserver variability is also high in the assessment of morphologic atypia, and atypical traits are not uncommon in plasma cells in MGUS.

Blood Cell Count↗
PubMed2001

Splenic marginal zone B-cell lymphomas: two cytogenetic subtypes, one with gain of 3q and the other with loss of 7q.

BACKGROUND AND OBJECTIVES: Splenic marginal zone B-cell lymphoma (SMZBCL) has clinical, immunophenotypic and histologic features distinct from other B-cell malignancies, but few chromosome studies have been previously reported. In the present study we performed conventional cytogenetics and in situ hybridization studies in 47 patients with SMZBCL. DESIGN AND METHODS: We studied 47 cases of splenic marginal zone B-cell lymphoma combining conventional cytogenetics and in situ hybridization (ISH) techniques using centromeric probes (chromosomes 3 and 12), locus specific probes (7q31 and 17p13) and cross-species color banding fluorescent ISH probes (RxFISH). The diagnosis of SMZBCL was ascertained in all cases after studying, morphologically and immunologically, peripheral blood and splenectomy specimens. RESULTS: A clonal chromosome abnormality detected by conventional cytogenetics and/or FISH was found in 33/47 patients (70%) being identified in 18 (18/33, 55%) as a complex abnormality. The most frequently recurrent abnormalities were: gain of 3q (10 cases), del(7q) (12 cases), and involvement of chromosomes 1, 8 and 14. No patient showed translocation t(11;14) (q13;q32) or t(14;18) (q21;q32). Trisomy 3 was detected in eight cases (8/47, 17%). Two novel cytogenetic abnormalities involving 14q32, t(6;14)(p12;q32) and t(10;14) (q24;q32) were reported. Deletion of 17p13 (P53) was observed by FISH in one case. Only one patient showed a gain of 3q or trisomy 3 and deletion 7q in the same karyotype. INTERPRETATION AND CONCLUSIONS: Our findings support the interpretation that two forms of SMZBCL could be considered, one with gain of 3q and the other with deletions at 7q.

Chromosome Aberrations↗
PubMed2001

The use of proximal femoral allografts in revision total hip arthroplasty.

The implant of a proximal femoral structural allograft is one of the possibilities to restore circumferential defects of multiply revised total hip arthroplasties. A review of 7 patients who underwent proximal femoral reconstruction with an allograft-prosthesis composite to restore bone loss in revision hip replacements is presented. The average follow-up period was 50.2 months. Two patients developed an infection and in one case an instability of the prosthesis appeared. Incorporation in the remaining 5 cases was/achieved in an average period of 8.2 months. Neither fractures nor high rate of resorption appeared in our series. The majority of patients have improved in the functional assessment. Despite the rate of complications, structural femoral allografts can be used with success in this difficult challenge of reconstructing major segmental bone loss of the proximal femur in revision hip surgery.

Arthroplasty, Replacement, Hip↗
PubMed1999

High-resolution autoreactive epitope mapping and structural modeling of the 65 kDa form of human glutamic acid decarboxylase.

The smaller isoform of the GABA-synthesizing enzyme, glutamic acid decarboxylase 65 (GAD65), is unusually susceptible to becoming a target of autoimmunity affecting its major sites of expression, GABA-ergic neurons and pancreatic beta-cells. In contrast, a highly homologous isoform, GAD67, is not an autoantigen. We used homolog-scanning mutagenesis to identify GAD65-specific amino acid residues which form autoreactive B-cell epitopes in this molecule. Detailed mapping of 13 conformational epitopes, recognized by human monoclonal antibodies derived from patients, together with two and three-dimensional structure prediction led to a model of the GAD65 dimer. GAD65 has structural similarities to ornithine decarboxylase in the pyridoxal-5'-phosphate-binding middle domain (residues 201-460) and to dialkylglycine decarboxylase in the C-terminal domain (residues 461-585). Six distinct conformational and one linear epitopes cluster on the hydrophilic face of three amphipathic alpha-helices in exons 14-16 in the C-terminal domain. Two of those epitopes also require amino acids in exon 4 in the N-terminal domain. Two distinct epitopes reside entirely in the N-terminal domain. In the middle domain, four distinct conformational epitopes cluster on a charged patch formed by amino acids from three alpha-helices away from the active site, and a fifth epitope resides at the back of the pyridoxal 5'-phosphate binding site and involves amino acid residues in exons 6 and 11-12. The epitopes localize to multiple hydrophilic patches, several of which also harbor DR*0401-restricted T-cell epitopes, and cover most of the surface of the protein. The results reveal a remarkable spectrum of human autoreactivity to GAD65, targeting almost the entire surface, and suggest that native folded GAD65 is the immunogen for autoreactive B-cells.

Amino Acid Sequence↗
PubMed1999

Association between educational level and health related quality of life in Spanish adults.

OBJECTIVE: To analyse differences in health by educational level in Spanish adults by comparing the health dimensions of the SF-36 Heath Survey. DESIGN: Data were taken from the National Survey on Drug Use carried out in February 1996. The information was collected by home personal interview. In addition to measuring the use of legal and illegal drugs and their associated health risks, the health status of the Spanish population was analysed using the Spanish version of the SF-36 Health Survey. MAIN OUTCOME MEASURE: Absolute and standardised differences between mean score on each dimension of the SF-36 Health Survey in each educational group with respect to the group with the highest educational level. RESULTS: Perceived health status declines with decreasing educational level, except in women with second level education who have a higher mean rating than women with third level education on various health dimensions. The absolute differences in perceived health between the different categories of educational level and the reference category become larger with increasing age. The greatest differences by educational level in both men and women were found in mental health and general health among persons 25 to 44 years of age, and in physical function and general health among those 45 to 64 years. In persons aged 65 or older, the greatest differences are seen in physical function and vitality in men, and in bodily pain and emotional role in women. CONCLUSIONS: The influence of educational level on the different dimensions of perceived health may vary by sex.

Adolescent↗
PubMed1999

Behaviour of bone allografts in the advancement of the tibial tuberosity.

In order to determine the behaviour of bone allografts in the advancement of the tibial tuberosity, we studied retrospectively 134 knees belonging to 119 recipients of frozen bone allograft for the treatment of a symptomatic patellofemoral osteoarthrosis. All patients had a 1.2-1.5 cm tibial tuberosity advancement with a release of the lateral patellar retinacula and no other additional surgery. Total incorporation of grafts took place in 116 cases (86.6%); graft resorption appeared in 16 patients (11.9%)(total resorption 3, and partial resorption 13). No disease transmission has been detected. To avoid donor site morbidity associated with harvesting iliac crest, the use of frozen bone allograft is a good alternative in the advancement of the tibial tuberosity.

Adult↗
PubMed1998

Differential uptake of myocardial perfusion radiotracers in normal, infarcted, and acutely ischemic peri-infarction myocardium.

OBJECTIVES: We measured the uptake of technetium-99m tetrofosmin (99m Tc) and thallium-201 (201 TI) in areas of healed transmural myocardial infarction and in the regions of acute peri-infarction ischemia. METHODS: Anesthetised pigs with a 1-month old transmural infarction elicited by permanent ligature of the left anterior descending (LAD) coronary artery below the first branch underwent one hour of proximal LAD occlusion followed by injection of 99m Tc-tetrofosmin and 201TI either in the left atrium (GI, n= 19) or in the jugular vein (GII, n = 6). Twelve other pigs (GIII) with similar acute peri-infarction ischemia received 99m Tc-tetrofosmin and 201Tl into the left ventricle during cardiocirculatory arrest to rule out the effect of coronary collaterals. Radiotracer counting was determined in samples from normal, acute ischemic and necrotic regions. RESULTS: Uptake of 99m Tc-tetrofosmin and 201 Tl was greater in the infarct scar (median % of normal tissue: 20 for 99m Tc and 8.6 for 201 Tl in GI; 22 and 15 in GII) than in acute ischemic myocardium (3.2 and 2.5 in GI; 6.4 and 3.3 in GII). Radiotracer injection in arrested hearts (GIII) depicted a similar pattern (median % of injected dose: 6.2 for 99m Tc and 10 for 201Tl in the scar; 2.3 and 4.0 in acute ischemia; 2.9 and 3.5 in normal tissue). The infarcted region showed connective tissue and lack of viable myocardium. CONCLUSION: A 1-month old infarct scar with no viable myocardial tissue can take up significant fractions of 99mTc-tetrofosmin and 201Tl even in the absence of coronary collateral perfusion. Data suggest that the infarct scar can extract these radiotracers from the intraventricular blood.

Animals↗
PubMed1998

Passive transmission of ischemic ST segment changes in low electrical resistance myocardial infarct scar in the pig.

OBJECTIVES: To analyze the passive electrical properties of a healed infarction and assess their role on transmission of contiguous ischemic ST segment potential changes. METHODS: We measured tissue resistivity (omega cm) at 1 kHz and the epicardial ST segment during 1 h of proximal reocclusion of the left anterior descending (LAD) coronary artery in 12 anesthetized pigs with one-month-old transmural infarction elicited by LAD ligature below the first branch. The impedance spectrum (1 to 1000 kHz) of normal and infarcted myocardium was measured in seven other pigs with similar infarctions. Electrical transmission of current pulses (30 microA) in infarcted tissue and in test solutions was also investigated. RESULTS: The infarct scar has a lower than normal resistivity (110 +/- 30 omega cm vs. 235 +/- 60 omega cm, p < 0.0001) and, unlike the normal myocardium, resistivity and phase angle of the scar did not change at increasing current frequencies, reflecting no capacitative response. LAD reocclusion induced a resistivity rise (510 +/- 135 omega cm, p < 0.01) and a ST segment elevation (0.6 +/- 0.7 to 9.5 +/- 5.1 mV, p = 0.002) in the ischemic peri-infarction zone, whereas the infarcted area showed ST segment elevation (0.5 +/- 0.5 to 3.8 +/- 2.6 mV, p = 0.03) with no resistivity changes. Potential decay of both ST segment and current pulses in the scar and in 0.9% NaCl solution was less than 1 mV/mm. Transmural deposition of connective tissue was seen in the center of the infarction. CONCLUSIONS: A one-month-old transmural infarction is a low resistance, noncapacitative medium that allows a good transmission of current pulses and of ST segment potential changes generated by contiguous peri-infarction ischemia.

Animals↗
PubMed1998

Troponin-T is a calcium-binding protein in insect muscle: in vivo phosphorylation, muscle-specific isoforms and developmental profile in Drosophila melanogaster.

Two sets of muscle polypeptides showing calcium-binding capacity and intense labelling in vivo with 32P were purified and characterized from Drosophila melanogaster adult extracts. The polypeptides exhibit crossed immunoreactivity and share similar biochemical properties such as those involved in purification. They have been identified as isoforms of troponin-T (TnT) by sequence analysis of a cDNA clone isolated from an embryonic library. The two sets of TnT polypeptides correspond to the fibrillar and non-fibrillar muscle isoforms, respectively. The non-fibrillar muscle isoforms separate into two bands which are differentially expressed during development. Analysis of TnT isoforms in bee thoraces indicates that the expression of the fibrillar muscle isoform correlates with the acquisition of functional flight capability. In vivo labelling experiments reveal that the two TnT sets are readily phosphorylated. The Drosophila TnTs show calcium-binding properties by three different types of assays. Our results suggest that this property could be specific to insect TnTs and may be related to the long, extremely acidic polyglutamic carboxy-terminus present in these polypeptides, which does not occur in non-arthropod TnTs.

Amino Acids↗
PubMed1998

Sex differences in mortality of people who visited emergency rooms for asthma and chronic obstructive pulmonary disease.

We assess the sex differences in mortality in a population-based cohort of those Barcelona residents older than 14 yr of age who received emergency room services (ERS) for either chronic obstructive pulmonary disease (COPD) or asthma, during the period from 1985 to 1989. Vital status was followed to the end of 1995. A total of 15,517 individuals, 9,918 males and 5,599 females were included in the study. Asthma was diagnosed in 16% of males and 53% of females. Overall, 50% of males and 30% of females died during the follow-up period. The mortality rates in both males and females who visited emergency rooms for COPD or asthma were significantly higher than the expected rates in the general population. These relative increases in the mortality rates were significantly higher in females than in males for both causes of death, COPD (age-adjusted female/male ratio = 2.39), and asthma (ratio = 3.95). However, survival was better in females than males among individuals in the study. The higher fatality in males than females was observed for all causes of death, all respiratory causes, and COPD (risk ratio among patients with COPD = 0.42, 0.29-0.59, and among patients with asthma = 0.11, 0.02-0.60), but not for asthma. Mortality for asthma was higher in females with a diagnosis of COPD (2.79, 1.52-5.13), but it was not different among individuals in whom asthma was diagnosed (1.02, 0.56-1.87). Greater severity of COPD in males than in females could explain a higher risk of dying for all respiratory causes and COPD in males. The increased risk of asthma death in females may be due to problems of coding the term "asthma" in death certificates. The higher rates in females than in males when comparing with the general population, may be an expression of a greater similarity in risk factors, such as smoking, in our population than in males and females of the general population.

Adolescent↗
PubMed1997

Identification of a genetic locus for familial atrial fibrillation.

BACKGROUND: Atrial fibrillation, the most common sustained cardiac-rhythm disturbance, affects over 2 million Americans and accounts for one third of all strokes in patients over 65 years of age. The molecular basis for atrial fibrillation is unknown, and palliative therapy is used to control the ventricular rate and prevent systemic emboli. We identified a family of 26 members of whom 10 had atrial fibrillation which segregated as an autosomal dominant disease. We subsequently identified two additional families in which the disease was linked to the same locus. METHODS: We screened the human genome with 300 polymorphic dinucleotide-repeat markers using an unconventional strategy of pooling the DNA samples into two groups (affected and unaffected), which reduced the sample size by approximately 90 percent, before performing linkage analysis to map the locus. This made it possible to identify potential loci within a few weeks. RESULTS: The lod scores for markers D10S569 and D10S607, located at 10q22-q24, were 3.60 in Family 1. The disease locus in Families 2 and 3 was also linked to the same markers, with lod scores of 6.02 and 5.35 for markers D10S569 and D10S607, respectively, when data on all three families were combined. Haplotype analysis of the three families showed that the locus was between D10S1694 and D10S1786, an interval of 11.3 centimorgans. CONCLUSIONS: Identification of the gene for familial atrial fibrillation will help to elucidate the molecular basis of the disease and provide insights into acquired forms. The strategy of pooling DNA samples for analysis is more time and cost effective than conventional screening and should accelerate the process of gene mapping in the future.

Adult↗
PubMed1997

Expression of adhesion molecules in 113 patients with B-cell chronic lymphocytic leukemia: relationship with clinico-prognostic features.

The B-cell chronic lymphocytic leukemia (B-CLL) is a heterogeneous disease, its clinical and biological behavior possibly being influenced by surface molecules expressed in B-lymphocytes. These molecules mediate cell adhesion, mobility and homing. Expression of surface adhesion molecules of the integrin family (CD11a/CD18 or LFA-1, CD11c/CD18), of the immunoglobulin-related family (CD54), of the selectin family (CD62L or LAM-1) and the lymphocyte homing receptor (CD44) were analyzed in peripheral cells from 113 B-CLL patients. The association with three prognosis-related parameters (Rai stage, bone marrow pattern and doubling time) was determined. The study included only patients with B-CLL lymphocytes of typical morphology, which always expressed CD5 and CD23. Low expression of integrins, particularly CD18, was associated with advanced disease (Rai stages III-IV) and diffuse bone marrow pattern, even after adjusting for other prognosis-related variables. Expression of CD54 was associated independently with rapid doubling time (less than 12 months). The association persisted after adjusting for stage and bone marrow pattern; CD44 was expressed in all patients. No correlations were found between expression of CD62L and the prognostic variables analyzed. In conclusion, CD54 expression and low CD18 expression are both significantly associated with poor prognostic features.

Adult↗