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Biomedical subjects

R Cabrera

Publications and source records attributed to R Cabrera.

At least 37 records · Page 2Linked to original sources
PubMed2002

CsA-based post-graft immunosuppression: the main factor for improving outcome of allografted patients with acquired aplastic anemia. A retrospective survey by the Spanish Group of Hematopoietic Transplantation.

A retrospective multicenter study was performed to assess the clinical results in patients with acquired aplastic anemia (AA) allografted over a 19 year period and to identify prognostic factors influencing survival. From April 1978 to December 1997, 176 patients were transplanted. Records from 160 receiving related matched bone marrow transplantation (BMT) were reviewed. Fifty-two percent of the patients were older than 20 years, 5% older than 40; 6.3% were untransfused at BMT and 56.2% had received prior treatments. Conditioning regimens were with chemotherapy in 43.7% of the procedures and with additional irradiation in 56.3%. Graft-versus-host disease (GVHD) prophylaxis was based on cyclosporin A (CsA) in 58.1% of the patients while methotrexate (MTX) was administered to 41.9%. Transplantation earlier on, a longer interval from diagnosis to BMT, GVHD prophylaxis with MTX, graft failure/rejection and acute severe GVHD were adverse factors for survival. The use of CsA emerged as the main factor for the improvement, inducing a significant decrease in graft failure/rejection rate and severe acute GVHD when compared with MTX alone. Radiation-containing regimens decreased the graft failure/rejection rate without improving survival due to the increased risk of acute GVHD. Age and number of transfusions pretransplant did not influence outcome. Survival achieved since 1991 is 79.79%, and graft failure and acute severe GVHD rates are 6.0% and 11.8%, respectively. In conclusion, CsA-based post-graft immunosuppression has been crucial in achieving improved survival in patients with acquired AA up to 40 years of age. Regardless of CsA use, further improvement in survival was apparent with time, probably due to better skills in patient care.

Adolescent↗
PubMed2001

Periodic maternal deprivation and lesion of anterodorsal thalami nuclei induce alteration on hypophyso adrenal system activity in adult rats.

The hypothalamic-pituitary-adrenal (HPA) axis is normally regulated by extrahypothalamic limbic structures, among these, the anterodorsal thalami nuclei (ADTN), which exert an inhibitory influence on HPA, in basal and acute stress conditions in rats. In the present work we have investigated whether neonatal maternal deprivation (MD) produces long-term changes in the ADTN regulation of HPA activity. Maternal deprivation, in female rats, for 4.5 hs daily, during the first 3 weeks of life, produced at 3 months old, a significant decrease in plasma ACTH concentration (p<0.001) and an increase in plasma corticosterone (C) (p<0.001), compared to control non-deprived rats (NMD). Also MD showed higher plasma epinephrine (E) and norepinephrine (NE) levels than NMD rats. The increase of NE (66.6% p<0.001) was higher than that observed in E (19%). After 30 days of ADTN lesion, plasma ACTH values were higher than in sham lesioned rats, in both NMD and MD animals. ACTH response was greater in MD rats. Plasma C, in NMD, was higher, whereas in MD lesioned animals, it was significantly lower than in sham lesioned. In MD rats, lesion produced a significant increase in plasma E and NE (p<0.001), and again, NE increase was higher than E increase. The more accentuated increase of NE than E, suggests sympathetic nervous system hyperactivity. In summary, neonatal maternal deprivation induces long-term alterations on HPA axis sensitivity and medullo adrenal secretion; enhanced sympathetic nervous system activity and, therefore affected the ADTN inhibitory influence on ACTH and adrenal glands secretion.

Adrenocorticotropic Hormone↗
PubMed2001

Autologous stem-cell transplantation for Hodgkin's disease: results and prognostic factors in 494 patients from the Grupo Español de Linfomas/Transplante Autólogo de Médula Osea Spanish Cooperative Group.

PURPOSE: To analyze clinical outcome and significant prognostic factors for overall (OS) and time to treatment failure (TTF) in a group of 494 patients with Hodgkin's disease (HD) undergoing autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS: Detailed records from the Grupo Español de Linfomas/Transplante Autólogo de Médula Osea Spanish Cooperative Group Database on 494 HD patients who received an ASCT between January 1984 and May 1998 were reviewed. Two hundred ninety-eight males and 196 females with a median age of 27 years (range, 1 to 63 years) received autografts while in complete remission (n = 203) or when they had sensitive disease (n = 206) or resistant disease (n = 75) at a median time of 26 months (range, 4 to 259 months) after diagnosis. Most patients received high-dose chemotherapy without radiation for conditioning (n = 443). The graft consisted of bone marrow (n = 244) or peripheral blood (n = 250). RESULTS: The 100-day mortality rate was 9%. The 5-year actuarial TTF and OS rates were 45.0% (95% confidence interval [CI], 39.5% to 50.5%) and 54.5% (95% CI, 48.4% to 60.6%), respectively. In multivariate analysis, the presence of active disease at transplantation, transplantation before 1992, and two or more lines of therapy before transplantation were adverse prognostic factors for outcome. Sixteen patients developed a secondary malignancy (5-year cumulative incidence of 4.3%) after transplantation. Adjuvant radiotherapy before transplantation, the use of total-body irradiation (TBI) in the conditioning regimen, and age > or = 40 years were found to be predictive factors for the development of second cancers after ASCT. CONCLUSION: ASCT achieves long-term disease-free survival in HD patients. Disease status before ASCT is the most important prognostic factor for final outcome; thus, transplantation should be considered in early stages of the disease. TBI must be avoided in the conditioning regimen because of a significantly higher rate of late complications, including secondary malignancies.

Adolescent↗
PubMed2001

Active idiotypic vaccination in a patient with biclonal follicular lymphoma.

Specific immunological responses to the idiotypic epitopes present in the surface immunoglobulin (Ig) of the clonal tumour population can be induced for active immunotherapy in patients with B-cell non-Hodgkin lymphoma (NHL). The clonality of the tumour cells should have important implications for the success of the implemented therapy. Here we report on the case of a patient enrolled in a protocol of active idiotypic immunotherapy in which previous cytofluorometric analysis showed a major IgM+, kappap+ population in the tumoral cell suspensions. However, sequence analysis of both tumour sample and tumour-derived hybrids revealed the presence of two unrelated clones that used different VH and VK gene segments. It was possible to obtain hybridomas secreting these two different IgM, kappap idiotypic proteins. The patient was immunised with a mixture of these two idiotypic Igs conjugated to keyhole limpet haemocyanin. Anti-idiotypic antibodies directed against both tumour-associated proteins were detected. This is the first case of anti-idiotypic therapy in a patient with a biclonal NHL. Our work calls attention to the question of clonality in the context of idiotypic vaccination in NHL patients.

Adult↗
PubMed2001

Defensive chemistry of Senecio miser.

Three eremophilanolides, 1alpha-acetoxy-8beta-methoxy-10betaH-eremophil-7(11)-en-8alpha,12-olide (1); 1alpha-angeloyloxy-6beta-hydroxy-8beta-methoxy-10betaH-eremophil-7(11)-en-8alpha,12-olide (2); and 1alpha-angeloyloxy-8betaH,10betaH-eremophil-7(11)-en-8alpha,12-olide (3), and two pyrrolizidine alkaloids, integerrimine (4) and its N-oxide (5), were isolated from bioactive fractions of Senecio miser. The structures of the new compounds 1 and 2 were established by NMR spectroscopic analysis and chemical transformation. The X-ray analysis of compound 1 was also performed. Eremophilanolides 1 and 2 and alkaloids 4 and 5 were found to be strong insect antifeedants, further supporting a proposed defensive role for these classes of compounds.

Animals↗
PubMed2001

Heliotropium huascoense resin exudate: chemical constituents and defensive properties.

From the resinous exudate of Heliotropium huascoense a new compound, rel-(8R,9R)-carrizaloic acid, (1) (3-[rel-(8R,9R-9-hydroxy-9,13,13-trimethyl-12-oxo-10-cyclohexenyl)methyl]-4-methoxybenzoic acid), and three known flavonoids, [3-methylgalangin, 3,7-dimethylgalangin, and (-)-alpinone] have been isolated. The structure of 1 was determined by spectral and chemical methods. Several plant defensive properties of 1 (insecticidal and antifungal) have been evaluated.

Animals↗
PubMed2001

Cord blood transplants: early recovery of neutrophils from co-transplanted sibling haploidentical progenitor cells and lack of engraftment of cultured cord blood cells, as ascertained by analysis of DNA polymorphisms.

The number of infused cells is a very important factor in cord blood transplant (CBT) engraftment. Prior ex vivo expansion of aliquots of transplanted cord blood (CB) units is being investigated as a procedure to increase engraftment potential, but results are difficult to evaluate due to a lack of markers for assessing the contribution of expanded cells. We transplanted five patients, infusing the best available CB unit and cells from a second donor simultaneously. In two patients, these cells were obtained from another frozen CB unit by CD34(+)positive selection and culture expansion; the other three patients received uncultured highly purified haploidentical CD34(+) cells. The first two patients had DNA from the culture expanded CB cells detected only for a few days around day +11 when the absolute neutrophil count (ANC) was >200/microl; thereafter and when the ANC was <500/microl, only donor DNA from the uncultured CB was detected. For the other three patients, DNA analysis showed early and transient granulocyte engraftment of haploidentical cells, progressively replaced by the CB-derived granulocytes. We concluded that: (1) simultaneous infusion of lymphocyte-depleted HLA highly mismatched haematopoietic progenitor cells has not produced unfavourable effects for CBT; (2) the double transplant model is suitable for evaluating the engraftment potential of ex vivocultured CB cells in the clinical setting; (3) the culture conditions used did not result in early recovery of ANC; and (4) co-transplantation of purified uncultured HLA haploidentical CD34(+) cells may reduce the time of neutropenia following CBT.

Acute Disease↗
PubMed2001

Frequency and determinants of microalbuminuria in mild hypertension: a primary-care-based study.

OBJECTIVE: To evaluate the frequency of microalbuminuria and its relationship with several risk factors and left ventricular mass in a population of mildly hypertensive subjects attended in a primary-care setting. DESIGN: Cross-sectional study. SETTING: Eight primary-care centres. PATIENTS: Two hundred and twenty-three non-diabetic patients recently diagnosed with mild hypertension were included in the study. None of them had clinical evidence of target-organ damage or had received prior antihypertensive treatment. INTERVENTIONS: Subjects included in the study underwent clinical interview, measurement of blood pressure (BP) on three visits, blood analysis, measurement of albumin by immunonephelometry in three overnight urine collections, 24 h BP monitoring and M-mode and Doppler echocardiography. MAIN OUTCOME MEASURES: Tobacco habit, clinic BP, body mass index, serum lipids and uric acid, glycaemia, urinary albumin excretion (UAE), ambulatory BP and left ventricular mass index. RESULTS: The frequency of microalbuminuria was 7.2%. Microalbuminuric patients were more likely to be men and to be characterized by higher ambulatory BP, body mass index and uric acid levels. Regression analysis demonstrated that male sex and 24 h systolic BP were determinants of UAE. Patients with white-coat hypertension showed lower UAE than did subjects with sustained hypertension. Although a certain relationship between UAE and left ventricular mass index was found, these variables were not significantly correlated. CONCLUSIONS: A low proportion of mildly hypertensive patients attended in a primary care setting are microalbuminuric. In this population, UAE is an expression of BP values over 24 h and correlates with several risk factors.

Adult↗
PubMed2001

[Severe caustic injuries of the esophagus: when to replace the esophagus].

From June 1985 to May 1998, 20 patients have been treated in our hospital by esophageal dilatations due to serious esophageal caustic stenosis. A retrospective analysis of these 20 patients was performed, evaluating age, sex, causative agent, number and time of dilatations, iatrogenic esophageal perforations, gastroesophageal reflux (GER) and psychological and social consequences. Follow-up has ranged from 1.5 to 14.5 years (mean = 8.07 years). The mean age at the time of accidental swallow was 42.2 months. The causative agent was dishwashing detergent in 11 patients and caustic soda in 9 patients. The mean of dilatations needed was 19.1 and the average duration of dilatations was 24.7 months. Seven patients had esophageal perforation during dilatation and none of them required surgical treatment. All patients had improvement of swallowing and an easier esophageal dilatation afterwards. Oral contrast studies demonstrated distortion of the esophago-gastric junction in the majority of patients. Ten patients were screened for GER with 24-hour esophageal pH monitoring in the first year postburn and it was pathological in 5. Antireflux surgery was carried out in 4 patients with a conspicuous improvement following surgery. Dilatations proved successful in 16 patients in less than two years, and in more than two years in 3 patients. The authors conclude that the majority of children with esophageal caustic stenosis can be managed successfully by esophageal dilatations, even with dilatation periods longer than two years or when an esophageal perforation occur during the procedure. The paramount importance of early diagnosis and treatment of GER is stressed.

Burns, Chemical↗
PubMed2001

[Colonic aganglionosis with ileal involvement. Ileocolic plasty].

During 1994 through 1999, we have treated five patients (3 boys, 2 girls) with total colonic aganglionosis (TCA) and ileal involvement. In three of them we performed a diverting ileostomy in the neonatal period and at the age of four and five months respectively in the remaining two patients, due to intestinal obstruction. In these two last patients a diagnosis of Hirschsprung's disease was made by anorectal manometry and rectal biopsies in the neonatal period. During laparotomy, a cutaneous ileostomy was created in all patients at the distal end of normal ileum, which was 30 to 110 cm (mean = 71 +/- 37 cm) from the ileocecal valve. After operation, a short bowel syndrome developed in three patients causing fluid and nutritional problems that required prolonged total parenteral nutrition (TPN). The definitive operative repair is performed at 4.5 to 14 months (mean = 8 +/- 3.7 months) by a 12 to 20 cm side-to-side ileocolostomy created between the ileum and aganglionic ascending color (Boley procedure) and ileorectal primary anastomosis (Rehbein procedure) using a circular stapler. Rectal dilatation, irrigation of the colon with saline, loperamide hydrochloride and resincholestyramine were begun in all patients postoperatively. Oral antibiotic prophylaxis, was given to the three patients who suffered from SBS. Oral feedings with semielemental diet were tolerated once stools were semiformed and TPN was discontinued at 8 to 34 days (mean = 21 +/- 1.7 days). postoperatively. After the definitive operation, enterocolitis developed in two patients, requiring one of them a short hospitalization during the episode. A possible explanation for the low incidence of enterocolitis in this series is the systematic postoperative use of irrigations of the colon with saline in all patients. These five patients have been followed-up for growth, development, bowel habit and continence. Follow-up has ranged from 15 to 62 months (mean = 32.2 +/- 19.2 months). Presently, all patients in this series have full enteral feeding and one to three bowel movements per day, with formed or semiformed stools. No patients is incontinent of stool. The patient's body weights (74 to 93%) and heights (89 to 92%) for their age were below average (four patients) or within normal range (one patient). Hemoglobin levels are within normal range in all patients. One patient has iron deficiency and another one has serum ferritin concentration below normal. Three patients have folic acid deficiency. Vitamin B12 absorption is normal in all patients. Although we can not conclude this is a better procedure than others, with is use we have obtained satisfactory results, with an excellent survival, scanty morbidity, a rapid return of bowel function and continence, and an acceptable physical development. During long-term follow-up, patients mus be evaluated for iron and folic acid deficiency.

Child↗
PubMed2000

The amount of free corticosterone is increased during lipopolysaccharide-induced fever.

The relation between lipopolysaccharide (LPS)-induced fever and bioavailability of corticosterone (B) was examined in male Wistar rats. Animals were injected with LPS (2.5 mg/kg i.p.) or saline and core temperature and heart rate were monitored continuously using a biotelemetry system. Blood samples were withdrawn from freely moving rats via jugular catheters for estimation of total and free plasma B. LPS induced a long-lasting increase (24-48 h) in core temperature and B secretion and a short-lasting increase (90 min) in heart rate. LPS-induced fever was accompanied by a significant increase in the free/total B ratio. In contrast, an acute injection of B, which resulted in circulating B levels similar to those found after LPS, did not affect the free/total B ratio. The important role of LPS-induced fever in the hormone secretion pattern and the equilibrium between free and total B was further demonstrated in an in vitro study showing that an increase in the temperature by 3 degrees C elevated the free B fraction and the free/total B ratio of plasma samples with concentrations of B in the physiological range (5-40 microg/dl). Taken together, these findings indicate that during LPS-induced fever there is an increase in the amount of biologically available B. Exposure of glucocorticoid-sensitive targets to elevated levels of free B could contribute to the restoration of homeostasis that is disturbed during inflammation.

Animals↗
PubMed2000

[Left ventricular diastolic dysfunction in young people with type 1 diabetes mellitus. Associated factors].

AIM: The aim of our study was to evaluate left ventricular function of diastolic in young (< 40 years) asymptomatic patients with type 1 diabetes mellitus free of cardiovascular disease symptoms and to analyze the associated factors to the left ventricular diastolic dysfunction (LVDD) in these patients. PATIENTS AND METHODS: Thirty-five type-1 diabetic patients (mean age 27.8+/-7.5 years) old and 54 healthy controls (mean age 26.1+/-4.1 years) were studied. Anamnesis, physical exploration, general analytical studies, microalbuminuric and Doppler-echocardiographic studies were performed. RESULTS: The LVDD was present in 13 (37.1%) of the diabetic patients and none of the control patients. The ratio of peak early to peak late (atrial) filling velocity was significantly decreased in diabetic compared with control subjects (1.1+/-0.3 versus 1.5+/-0.2; p<0.01). The isovolumetric relaxation time was increased in diabetic patients compared with control subjects (104+/-11 versus 79+/-11; p<0.01). Diabetics with LVDD were older aged, predominantly males, had worse glucemic control, more alteration of lipidic metabolism and higher levels of microalbuminuria, than diabetics without LVDD. CONCLUSIONS: The LVDD is frequent in young diabetics free of cardiovascular disease symptoms. These studies suggest that because this patients were of older age, of the masculine sex with, poor glucemic control, altered lipidic metabolism, and microalbuminuria they might be a group that is associated with LVDD which, in the absence of cardiovascular disease, might be an early preclinical alteration, potentially related to subsequent development of diabetic cardiomyopathy.

Adolescent↗
PubMed2000

Autoantibody activity of the immunoglobulin secreted by a follicular B-cell lymphoma.

In patients with B-cell lymphoma, only in rare cases a secreted paraprotein is found, and in very few of them an associated autoantibody activity has been demonstrated. Here we report the case of a patient with a low-grade B-cell lymphoma with a serum biclonal paraprotein (G,M)lambda and severe erythroblastopenia. Indirect immunofluorescence studies of total serum revealed cytoplasmic (Hep-2 cells) and extracellular matrix (rat tissue sections) staining, suggestive of a new specificity. After gel filtration of serum samples, only the IgM-containing fraction showed the same pattern of staining. Tumor-derived hybridomas expressed an unmutated V3-11 gene identical to that found in tumor samples and secreted an IgM immunoglobulin endowed with the same reactivity, which confirms the tumoral origin of the tissue-reactive protein. The results suggest a link between the autoimmune condition in this patient and the novel specificity displayed by the tumor-derived immunoglobulin.

Adult↗
PubMed2000

Evaluation of engraftment of ex vivo expanded cord blood cells in humans.

Cord blood transplants (CBT) result in high rates of engraftment in patients transplanted because of inherited diseases even across marked HLA disparities, mostly in children, with less severe manifestations of GVHD than BM and PBSC transplants. Evaluation of engraftment potential of CBT based on early progenitor content is difficult due to their inaccurate quantification. Instead, post-thaw nucleated cell counts (Pt-NCC) are commonly used for this purpose. We have analyzed engraftment as a function of pre-freeze nucleated cell counts (Pf-NCC) in patients receiving CBT because of inherited diseases. We have observed median times to engraftment of 26 days or less, shortest times ranging 8 to 13 days, late engraftment or graft failures tending to be associated with age >15 years and infusions of <3.7 x 10(7)/Pf-NCC/kg. These data may be appropriate references to evaluate engraftment of CBT performed with previously ex vivo expanded cells. CBT performed with units of which one aliquot has been previously culture-expanded have resulted in times to engraftment similar to the ones observed in the above-mentioned analysis. In these trials it is not possible to trace the actual origin of the early engrafting cells because the pre-cultured cells lack differentiating markers. To better evaluate the engraftment dynamics of culture-expanded CB cells in humans, we have used a model of simultaneously transplanting cells from two different donors to the same patient. Preliminary results of patients that have simultaneously received one uncultured CB unit and culture-expanded purified CB CD34+ cells obtained from a second one show no significant contribution of cultured cells to early engraftment, and no prohibitive unfavorable immunological problems have been observed.

Adolescent↗
PubMed2000

Infusion of lymphocytes obtained from a donor immunised with the paraprotein idiotype as a treatment in a relapsed myeloma.

A 48-year-old patient with IgA k multiple myeloma received a BMT from his HLA-matched sibling. After transplantation, the disease relapsed. Melphalan therapy followed by reinfusion of haemopoietic blood stem cells collected from the patient led to the improvement of the clinical status, although mixed chimerism and an elevated serum IgA persisted. Successful donor immunisation against an immunogenic preparation of the recipient monoclonal protein was performed before the infusion of donor T lymphocytes (DLI) into the patient. Ten weeks after the lymphocyte infusions, no monoclonal band was evidenced and donor complete chimerism was detected. The patient did not develop GVHD. Once complete remission was achieved, the idiotype vaccine was administered to the patient. Nineteen months after DLI, the patient remains in remission. Bone Marrow Transplantation (2000).

Antineoplastic Agents, Alkylating↗