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Biomedical subjects

A Sastre

Publications and source records attributed to A Sastre.

At least 19 recordsLinked to original sources
PubMed2005

Long-term outcome of allogeneic or autologous haemopoietic cell transplantation for acute lymphoblastic leukaemia in second remission in children. GETMON experience 1983-1998.

We present a retrospective study of long-term outcome and predictive factors of survival and relapse in 219 paediatric patients with acute lymphoblastic leukaemia (ALL) in second remission. They received allogeneic (allo) or autologous (auto) haemopoietic cell transplantation (HCT) depending on the availability of a matched sibling donor. The probability of event-free survival (EFS) for the total patient group was 0.35+0.03 at 14 years. No significant differences were observed for EFS between allo- and auto-HCT: 0.39+0.05 vs 0.32+0.04 (P=0.43). A better EFS was seen in patients with a late relapse (LR) (P=0.06 and 0.02, for allogeneic and autologous respectively). Significantly better EFS was observed in allo-HCT patients under 10 years of age and in auto-HCT patients with leukocytes at diagnosis below 25 x 109/l and late relapse. Predictive factors of failure in both groups were early relapse (ER), medullary relapse and age over 10 years. The probability of relapse (RP) for the total group of patients was 0.57+0.03, and it was significantly higher in auto-HCT patients: 0.65+0.04 vs 0.42+0.06 (P=0.002). Factors predictive for relapse were medullary and early relapse, auto-HCT and WBC >25 x 109/l at diagnosis.

Child↗
PubMed2004

Long-term results of high-dose chemotherapy and autologous stem cell rescue for high-risk neuroblastoma patients: a report of the Spanish working party for BMT in children (Getmon).

The authors retrospectively analyzed the long-term outcome of 67 patients over 1 year of age at diagnosis with high-risk neuroblastoma (stage 4 or stage 3 with N-myc amplification) who were treated with megatherapy and stem cell rescue from 1984 to 1998. Median age at transplant was 4 years (range 1.6-15 years). The source of cells was peripheral stem cells in 29 and bone marrow in 38 patients. In 12 patients, an in vitro purging of bone marrow harvest was performed. Most patients were conditioned with melphalan, BCNU, and VM-26. After transplant 19 patients received complementary treatment with IL-2 (16) or 13-cis-retinoic acid (3). Six patients (8%) died from transplant-related toxicity and 39 from disease progression. Three patients were alive with active disease at the time of analysis. Nineteen patients are alive and disease-free at a median follow-up of 104 months. Five-year event-free survival is 0.30. Survival of patients who received a purged graft was not significantly better than the rest. Post-transplant complementary treatment significantly improved overall and event-free survival (p = .01 and p = .04, respectively).

Adolescent↗
PubMed2004

Analysis of factors affecting PBPC collection in low-weight children with malignant disorders.

BACKGROUND: PBPC collection in children weighing </=25 kg is hampered by technical and clinical problems related to vascular access, low total blood volume, anticoagulation, side effects, and psychological impact. The aim of this study was to analyze several clinical and technical factors, other than pre-apheresis CD34(+) count, that may affect PBPC collection in these low-weight children. METHODS: Data from 88 leukaphereses performed in 45 children were analyzed, including pre-apheresis CD34(+) cell count, COBE Spectra software (version 4.7 versus 6.0), apheresis volume [standard versus large-volume leukapheresis (LVL)] and patient's diagnosis, age, weight and sex. RESULTS: The median number of PBPC collected was 6.68 mononuclear cells (MNC)x10(8)/kg (range 2.36-19.05) and 1.69 CD34(+) cellsx10(6)/kg (range 0.08-13.79). Multivariate analysis showed that factors independently associated with the CD34(+) cell yield per apheresis were pre-apheresis CD34(+) cell count (P<0.001), diagnosis (P=0.008) and apheresis volume (P=0.009). Recruitment of CD34(+) cells was also independently affected by the apheresis volume, being higher in the LVL group (P=0.008). DISCUSSION: We have demonstrated that, apart from the well-known influence of the pre-apheresis CD34(+) cell count, two other factors have a major impact on the CD34(+) cell yield: patient's diagnosis and apheresis volume. In addition, taking into account that side effects were mild and tolerable, we have confirmed that LVL is a safe and effective procedure in children </=25 kg, and that AutoPBSC software could be reliably used in these patients, provided that an experienced team performs the procedure.

Antigens, CD34↗
PubMed2004

[Congenital neuroblastomas].

BACKGROUND: We consider congenital neuroblastomas (CN) those detected in pregnancy or at the very first hours of life. Due to perinatal sonography, its incidence has increased in the last years. We present herein our experience in the treatment of this condition and we try to find out any different clinical pattern from those neuroblastomas diagnosed later in life. METHODS: We review the CN treated in our hospital from 1990 to 2003, analyzing diagnosis, localization, tumor staging, N-myc amplification, treatment and evolution. RESULTS: Among the 107 neural tumors managed during this period (89 neuroblastomas, 18 ganglioneuromas), 8 were congenital neuroblastomas (7 girls, 1 boy). Two patients had prenatal diagnosis and 6 tumours were detected in routine exploration or casual findings upon neonatal examination. Six were abdominal, 1 thoracoabdominal and 1 abdominopelvic with dumbbell invasion. Three tumours were classified like stage 1, 1 stage 2, 1 stage 3, 1 stage 4 and 2 stage 4S. Although most of them had unfavorable histology, we didn't find N-myc amplification in any tumor. All patients were operated upon, with preoperative chemotherapy in 2 of them. Resection was complete in 7 out of the 8 tumors. The patient who presented neurological symptoms at birth recovered neither motility nor bladder function after resection. All of them survive after 60+/-53 months of follow-up. CONCLUSIONS: The outcome in this group of neuroblastomas is better that expected, probably because of its abdominal location. On the contrary in dumbbell neuroblastomas, neurological damage at birth seems to be irreversible.

Female↗
PubMed2003

Evaluation of two different oestrus-synchronisation methods with timed artificial insemination and resynchronisation of returns to oestrus in lactating Holstein cows.

To examine the outcomes of adding medroxyprogesterone acetate (MAP) to the ovsynch protocol with the traditional ovsynch protocol in both cycling and anoestrus cows, and to evaluate a resynchronisation protocol, 742 cows averaging more than 40 days postpartum were assigned to the following four treatments: (1) ovsynch (OVS): day 0: GnRH; day 7: PGF2alpha; day 9: a similar dose of GnRH; day 10: timed artificial insemination (TAI), approximately 16-20h later; (2) ovsynch+MAP (MAP): the same ovsynch protocol plus an intravaginal insert made of polyurethane sponge impregnated with 300mg of MAP immediately after the first GnRH treatment and on day 7, at the time of the PG treatment, the sponge was removed; (3) resynchronisation (MAP+ODB): 1mg of oestradiol benzoate (ODB) on day 13 after TAI and a new sponge impregnated with MAP was inserted and; on day 20, 1mg of ODB was given and the sponge removed; and (4) no resynchronisation (No MAP): only oestrus detection and AI at any repeat oestrus detected after TAI. Progesterone was measured in milk samples collected on days -17, -10, -3, 13 and 20 (TAI=day 0). Based on milk P4 at days -17 and -10, 27.4% of the cows were still anoestrus. At PG injection, 67.7% of the cycling and 21.3% of the anoestrus cows had elevated P4. Farm, days postpartum and parity variations were detected in both cases. On day 20 after TAI 42.6% of cycling and 8.3% of the anoestrous cows had elevated P4. Pregnancy rates were similar in both pre-breeding treatments (20%), but interactions (P<0.001) were detected between treatment and cycling activity (for anoestrous cows: MAP=34.9%; OVS=11.1%. Average interval from TAI to subsequent AI was 37+/-3 days. Resynchronisation resulted in more (P<0.001) cows in oestrus between days 18 and 25 after TAI. Conception rate in the MAP+ODB treatment was lower (P<0.05) than the No MAP group (22.8% versus 47.4%). It was concluded that the addition of a progestin to the ovsynch protocol resulted in increased pregnancy rates of cows treated during anoestrus. The benefit of including MAP with the ovsynch protocol for cycling cows is equivocal.

Administration, Intravaginal↗
PubMed2002

Influence of apolipoprotein E polymorphism on plasma vitamin A and vitamin E levels.

BACKGROUND: Plasma concentrations of vitamins A and E are positively correlated with those of concurrent lipids and, on the other hand, lipid levels are influenced by apolipoprotein E polymorphism. Therefore, the effect of this polymorphism on both vitamins was analysed in an adult population. MATERIALS AND METHODS: Subjects were recruited from a working population. Their anthropometric, lifestyle and dietary intake variables and menopausal status were recorded. Their apolipoprotein E phenotype and their plasma vitamins A and E (by high-performance liquid chromatography) and lipid (enzymatically) concentrations were determined after an overnight fast. The associations of the phenotype with vitamins and lipids were studied in men and women separately and controlling for significant covariates. RESULTS: The apolipoprotein E phenotype was associated with the concentrations of total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol in women, whereas no associations with lipids were found in men. Vitamin A and vitamin E levels were higher in men than in women, but only the difference in the former persisted after lipid adjustment. Apolipoprotein E2 slightly increased vitamin A levels in women, an effect which was still evident with lipid adjustment. Actually, both the apolipoprotein E phenotype and triglyceride were selected as significant predictors of this vitamin by multiple regression. This phenotype did not affect vitamin E levels in either sex. CONCLUSIONS: Lipids do not mediate the effect of gender on vitamin A levels. Apolipoprotein E polymorphism is an independent determinant of vitamin A levels in women. Pending confirmation by others, we propose that enhancement of this vitamin may contribute to the beneficial impact of the epsilon2 allele on human ageing and health.

Adult↗
PubMed2001

[Results of treatment with 2-chlorodeoxyadenosine in refractory or relapsed Langerhans cell histiocytosis. Study of 9 patients].

BACKGROUND: To analyse the results of the treatment with 2-chlorodeoxyadenosine (2CdA) in 9 patients with refractory or relapsed Langerhans cell histiocytosis (LCH) tracted in 8 Spanish hospitals between 1993 and 1999. PATIENTS AND METHOD: In the 9 patients the following data were recorded: age, sex, organ involvement by LCH, first treatment and response, dose, number of cycles and schedule of administration 2CdA, response to 2CdA treatment, toxicity, disease-free survival (DFS) and overall survival (OS). RESULTS: Median age was 25 years (range, 6-63). All patients had multiorganic involvement by LCH, with severe organ dysfunction in 4. 2CdA was administered as second line treatment in 7 cases and as third line in 2. The 2CdA dose was 0.1 mg/kg per day during 5 days in the majority of patients, and interval between cycles was 4 weeks. In 2 cases a complete remission (CR) was achieved and 4 cases attained a partial remission (PR) (overall response rate 66%). The main toxicity was hematologic, with neutropenia grade > 2 in 5 cases and thrombocytopenia > 2 in 5. Four patients had infections, with fatal evolution in one of them. After a median follow-up of 8 months (range 2-17), 2 patients remained in CR (12 months both), 4 in PR (range 2-12 months) and one had active disease (17 months). The other two died due to progressive disease and Aspergillus spp. sepsis, respectively. The actuarial probabilities of DFS and OS were 58% (95% CI, 38-78%) and 71% (95% CI, 54-88%), respectively. CONCLUSIONS: 2CdA is an active drug for patients with refractory or relapsed LCH, and its main toxicity is myelosuppression. The usefulness of 2CdA, isolated or in combination with other drugs, in patients with refractory or relapsed LCH must be assessed in controlled studies.

Adolescent↗
PubMed2001

Melatonin and 6-OHMS in high-intensity magnetic fields.

We determined if all-night exposure to 60 Hz magnetic fields at an intensity well within the upper range of occupational exposures (resultant intensity = 127.3 microTesla [muT]) resulted in suppression of melatonin or its major metabolite 6-hydroxymelatonin-sulfate (6-OHMS) in the first-void morning urine of 24 healthy male volunteers. Measures collected after continuous and intermittent magnetic field exposure test conditions were compared to similar measures collected after an equivalent no-exposure control condition. Urinary concentrations of melatonin and 6-OHMS did not differ as a function of type of magnetic field exposure, nor did they differ between field exposure and control conditions. These results demonstrate that the nocturnal secretion and metabolism of melatonin are not altered in humans by field exposure at an intensity over 600 times higher than that typically encountered in the home.

Adult↗
PubMed2001

All-night exposure to EMF does not alter urinary melatonin, 6-OHMS or immune measures in older men and women.

Healthy men (n = 22) and women (n = 24), 40-60 years of age, were exposed all-night (23:00-07:00 hr) to 60-Hz magnetic fields at an intensity (resultant flux density = 28.3 microTesla [microT]) well within the occupational-exposure range, or sham exposed under equivalent, counter-balanced, no-exposure ( < or = 0.2 microT) control conditions. Concentrations of melatonin, and the major metabolite of melatonin, 6-hydroxymelatonin-sulfate (6-OHMS), in first-void morning urine were not altered in either gender by exposure to the magnetic field, compared to control conditions. Statistical analysis also failed to reveal any evidence for exposure-related alterations in blood concentrations of multiple hematologic and immune system parameters (CD3, CD4, CD8, natural killer [NK] cells). The present results replicate and extend earlier negative findings based on the exposure of young men to power-frequency magnetic fields.

Adult↗
PubMed2001

Examination of the melatonin hypothesis in women exposed at night to EMF or bright light.

It has been hypothesized that the increased incidence of breast cancer in industrial societies is related to greater exposure to power-frequency electric and magnetic fields (EMF) and/or the presence of high levels of light at night (LAN). EMF and LAN are said to reduce circulating levels of the hormone melatonin which, in turn, allows estrogen levels to rise and stimulate the turnover of breast epithelial stem cells and increase the risk for malignant transformation. Three laboratory-based studies, in which a total of 53 healthy young women were exposed at night to EMF or to LAN under controlled exposure conditions, were performed to determine whether such exposures reduce melatonin and are associated with further alterations in estrogen. All-night exposure to industrial-strength magnetic fields (60 Hz, 28.3 microT) had no effect on the blood levels of melatonin or estradiol. In contrast, nocturnal melatonin levels were profoundly suppressed, and the time of peak concentration was significantly delayed in women exposed to LAN, regardless of whether they were in the follicular or luteal phase of the menstrual cycle. These changes, however, were not associated with alterations in point-for-point matching measures of estradiol. Women who chronically secrete high or low amounts of melatonin each night (area-under-curve range: 86-1,296 pg/mL) also did not differ in their blood levels of estradiol. Taken together, these results are consistent with a growing body of evidence which generally suggests that environmental EMF exposure has little or no effect on the parameters measured in this report.

Adult↗
PubMed2001

Side effects of low-dose pyridostigmine bromide are not related to cholinesterase inhibition.

BACKGROUND: Pretreatment with pyridostigmine bromide (PB) has become part of standard military procedures for protection against the effects of possible chemical warfare attack. The purpose of the work reported here was to quantify the type, intensity and frequency of side effects of low-dose PB, and to examine factors that predict the intensity and frequency of side effects. METHOD: A double-blind, cross-over, placebo (PL)-controlled design was used. Of the 67 subjects, 33 received 30 mg PB every 8 h for 13 doses, and 34 received 60 mg on the same schedule. Order of PB and PL administration was counterbalanced. RESULTS: Overall, side effects were mild, even at the 60-mg dose level. More side effects were reported when volunteers were taking PB than when they were taking placebo. Women reported more symptoms than men. Neither cholinesterase inhibition nor plasma levels of PB predicted side effect scores during the PB week; the best predictor of side effect scores during the PB week was side effect scores during the PL week. CONCLUSION: PB is well tolerated by healthy young people, even when twice the recommended military dose is administered.

Adolescent↗
PubMed2000

Synthesis and electrochemical properties of phthalocyanine--fullerene hybrids

Phthalocyanines linked to C60 have been synthesized by two general strategies. One of them involves the addition of an azomethine ylide prepared in situ from a formyl phthalocyanine to C60, and the other one involves a statistical condensation of two substituted phthalonitriles, one of them bearing the C60 moiety covalently attached. These new phthalocyanine-fullerene dyads have been studied by cyclic voltammetry and Osteryoung square wave voltammetry, and inter- and intramolecular electronic interactions between the two electroactive subunits have been demonstrated.

Journal Article↗
PubMed2000

High survival rate in infant acute leukemia treated with early high-dose chemotherapy and stem-cell support. Groupo Español de Trasplante de Médula Osea en Niños.

PURPOSE: Infants with acute leukemia have a poor prognosis when treated with conventional chemotherapy. It is still unknown if stem-cell transplantation (SCT) can improve the outcome of these patients. In the present study, we review our experience with SCT in infant acute leukemia to clarify this issue. PATIENTS AND METHODS: We report the results of 26 infants who were submitted to a SCT for acute leukemia. There were 15 cases of acute myeloid leukemia and 10 cases of acute lymphoid leukemia. One patient had a bilineal leukemia. Twenty-two patients were in their first complete response (CR1), three were in their second CR, and one was in relapse. Eight patients were submitted to allogeneic SCT, and 18 underwent autologous SCT. RESULTS: With a median follow-up of 67 months, the 5-year overall survival and disease-free survival (DFS) are 64% (SE = 9%) and 63% (SE = 10%), respectively. Autologous and allogeneic SCT offered similar outcome. There was not any transplant-related mortality, and all deaths were caused by relapse in the first 6 months after SCT. In multivariate analysis, the single factor associated with better DFS was an interval between CR1 and SCT of less than 4 months (P: <.025). CONCLUSION: SCT is a valid option in the treatment of infant acute leukemia, and it may overcome the high risk of relapse with conventional chemotherapy showing very reduced toxicity. This study suggests that SCT should be performed in CR1 in the early phase of the disease.

Acute Disease↗
PubMed2000

Nocturnal magnetic field exposure: gender-specific effects on heart rate variability and sleep.

OBJECTIVE: To determine if controlled exposure to power-frequency magnetic fields alters heart rate variability (HRV) and polysomnographic endpoints in healthy men (n=22) and women (n=24), 40-60 years of age. METHODS: A randomized, double-blind, crossover design was used. Study endpoints collected during all-night exposure to 60 Hz magnetic fields at an occupational intensity (resultant flux density=28.3 microTesla, microT) were compared to similar endpoints obtained under equivalent, counterbalanced, no-exposure (< or =0.2 microT) control conditions. RESULTS: Older men, but not women, exposed to the magnetic fields showed power reductions in the LF band of the HRV frequency spectrum, which is associated with sympathetically-mediated blood pressure and thermoregulatory control (P<0.04). Older women, but not men, exposed to the fields showed a pattern of disrupted sleep, with reductions in the duration of REM sleep (P=0.03), and strong trends for reductions in sleep efficiency (P=0.06) and total sleep time (P=0.06). CONCLUSIONS: The gender-specific effects seen here with older volunteers replicate the results of previous exposure studies with younger men and women.

Adult↗
PubMed2000

Brain frequency magnetic fields alter cardiac autonomic control mechanisms.

OBJECTIVE: Heart rate variability (HRV) is a noninvasive indicator of sympathetic and vagal cardiovascular control known to be tightly correlated with sleep stages. Recent studies indicate that HRV in humans is altered by nocturnal exposure to power-frequency (60 Hz) magnetic fields. Given the central origin of autonomic cardiac control, we determined if field exposure in the beta(1) EEG/MEG frequency range was a more effective stimulus for HRV alteration than 60 Hz fields, and explored the mechanisms involved. METHODS: Healthy young men were exposed (n=9) overnight to an intermittent magnetic field (16 Hz, 28.3 microTesla, microT), or sham exposed (n=9), under blind test conditions in a laboratory exposure facility. RESULTS: Field exposure was associated (P<0.05) with reduced power in the low band of the HRV frequency spectrum, and with decreases in mean heart rate. Analysis of the timing of the R waves surrounding each on-off transition of the intermittent field revealed no evidence for a direct effect on the cardiac pacemaker. CONCLUSIONS: Magnetic field exposure in the EEG/MEG beta(1) frequency range alters HRV via a CNS effect. Phase-resetting experiments rule out a direct effect on the cardiac pacemaker. Biophysical calculations of the intensity of the electric fields induced in brain versus heart under the present exposure conditions are also consistent with and support a central rather than a peripheral site of action.

Adult↗