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M Martinez

Publications and source records attributed to M Martinez.

At least 73 records · Page 4Linked to original sources

Early and delayed consolidation chemotherapy significantly improves the outcome of children with intermediate risk acute lymphoblastic leukemia. Final results of the prospective randomized PETHEMA ALL-89 TRIAL.

BACKGROUND AND OBJECTIVES: To evaluate the impact of early and delayed consolidation chemotherapy on the outcome of children with acute lymphoblastic leukemia (ALL) stratified according to risk groups. DESIGN AND METHODS: From 1989 to 1994, 195 children (< or = 15 years old) diagnosed as having ALL (ALL-L3 excluded) in 15 Spanish hospitals entered the prospective, randomized PETHEMA ALL-89 trial. Patients were stratified into low-risk (LR), intermediate-risk (IR) and high-risk (HR) groups according to their initial features and the rate of response to induction therapy. LR-ALL patients were randomized to receive or not early consolidation chemotherapy (C-1). After receiving C-1, IR patients were randomized to receive or not delayed consolidation chemotherapy (C-2). HR patients received C-1 and C-2 chemotherapy. Standard maintenance chemotherapy was administered to all patients for 2 years. High doses of intravenous methotrexate and 12 triple intrathecal doses were given as prophylaxis against central nervous system (CNS) disease. RESULTS: The mean (and standard deviation) age was 6 (4) years and 120 patients were males. Fourteen patients had early pre-B-ALL, 149 common or pre-B-ALL, and 32 T-ALL. Complete remission (CR) was attained in 189 patients (97%), 11 of whom (6%) had a slow response. Risk group stratification after CR was: LR 89, IR 50 and HR 56 patients (including a subset of 26 patients at very high risk). Ten-year event-free survival (EFS) and overall survival (OS) probabilities for the whole series were 58% (95% CI: 52-64%) and 69% (61-77), respectively, with a median follow-up of 8.7 years. Dividing the patients according to risk group, the 10-year EFS and OS probabilities in the LR group were 71% (63-79) and 86% (80-92), respectively; in the IR group 69% (57-81) and 76% (64-88), respectively, and in the HR group 30% (18-42) and 44% (32-57), respectively. For LR patients receiving C-1, EFS and OS were 79% (57-92) and 90% (82-98), respectively, versus 62% (48-76) and 66% (51-81) in patients not receiving C-1 (p= 0.06). For IR patients, EFS and OS were significantly improved in those receiving early and delayed consolidation (EFS 87% (74-88) vs. 52% (41-70), and OS 92% (87-97) vs. 61% (51-71)(p=0.036). Prognostic factors for EFS identified in multivariable analyses were: age >10 years in the LR group (OR 3.5, 95% CI 1.3-9.5, p=0.01), and treatment with C-2 in IR patients (OR 5.0, 95% CI 1.4-17.8, p=0.01). The CNS relapse rate was 4% for all the series (including the HR subset). Tolerance to treatment was good. INTERPRETATION AND CONCLUSIONS: In this study, early consolidation seemed to improve the prognosis of children with LR-ALL, but differences in EFS were not significant. Delayed consolidation had a favorable influence on the outcome of IR-ALL. CNS preventive treatment without cranial irradiation was effective in all the groups of ALL patients.

Antineoplastic Combined Chemotherapy Protocols↗

Morphology of the seminal vesicle of Calomys callosus submitted to experimental chronic alcoholism.

The objective of the present study was to assess the possible toxic effects of chronic alcohol ingestion on the ultrastructure of the lining epithelium of the seminal vesicle of the rodent Calomys callosus, in order to contribute to the understanding of the consequences of alcohol abuse for the morphology of the male reproductive apparatus. Twenty six adult animals aged three months were divided into two experimental groups. The control group received a solid diet (Purina chow) and tap water, and the alcoholic group received the same solid diet and ethanol P.A. diluted 20% in water (v/v). After 210 days of treatment, all animals were anaesthetised, weighed and sacrificed. At the end of treatment, mean body and seminal vesicle weight did not differ between control and alcoholic animals. The epithelial cells of the alcoholic group showed many alterations such as the presence of lipid droplets of different sizes, nuclei with increased peripheral chromatin and greater electrondensity, megamitochondria, and intense dilatation of the cisterns of the granular endoplasmic reticulum. It was concluded that 20% ethanol provokes marked ultrastructural lesions in the seminal vesicle.

Alcoholism↗

Discrete dinuclear cyano-bridged complexes.

The cyano-bridged complexes [L14CoIIINCFeII(CN)5]-, [L14CoIIINCFeIII(CN)5], [L15CoIIINCFeII(CN)5]-, and [L15CoIIINCFeIII(CN)5] (L14 = 6-methyl-1,4,8,11-tetraazacyclotetradecan-6- amine, L15 = 10-methyl-1,4,8,12-tetraazacyclopentadecan-10-amine) are prepared and characterized both structurally and spectroscopically. In each complex, the pendant amine is trans to the bridging CN ligand, as determined by spectroscopy and X-ray crystallography: Na(trans-[L14CoIIINCFeII(CN)5]).8H2O, monoclinic space group P2(1)/c, a = 15.58(1) A, b = 19.797(4) A, c = 19.830(6) A, beta = 91.62(4) degrees, Z = 8; trans-[L14CoIIINCFeIII(CN)5].4H2O, monoclinic space group P2(1)/m, a = 9.9690(9) A, b = 13.316(1) A, c = 10.1180(8) A, beta = 90.720(6) degrees, Z = 2; [L15CoIIINCFeIII(CN)5].4H2O, triclinic space group P1, a = 9.454(1) A, b = 9.778(1) A, c = 9.865(2) A, alpha = 60.37(1) degrees, beta = 62.60(1) degrees, gamma = 65.82(1) degrees, Z = 1. A precursor to the 14-membered macrocyclic complexes is prepared for the first time, and its crystal structure is also reported: trans-I [CoL14Cl](ClO4)2, orthorhombic space group Pbca, a = 11.833(3) A, b = 13.363(2) A, c = 26.015(2) A, Z = 8. These compounds form part of a novel series of discrete CN-bridged dinuclear compounds. The mixed-valent CoIII-FeII compounds exhibit metal-to-metal charge-transfer (MMCT) transitions in the region 510-530 nm.

Journal Article↗

Outpatient surgical unit: critical review after the first year of operation.

Introduction: Outpatient surgery has been quickly accepted by many hospitals, showing a lot of advantages, both in the quality of health care and also in hospital management. Following this trend, our Hospital started operating an Outpatient Surgical Unit in May 1997. Objectives: Once we had reached our 'cruising speed', we thought it wise to make a critical review of our experience. Material and methods: We have reviewed 331 patients who underwent surgery during the first year of operation, with special attention to the acceptance of this type of surgery by the population in general, and to the changes in pre-operative and post-operative protocols that this process has caused. Results: The rate of admission was 3.02%, and all of them occurred after 24 h. We found 57 minor complications (spotty dressing, mild inflammatory signs) on the first day assessment, but only 16 patients had refered complications. 91.5% of the questionnaires sent back by the patients qualify the experience as good or excellent. Conclusions: Outpatient Surgery is a good solution for many surgical pathologies, as it is well accepted by the general population. Inclusion and exclusion parameters regarding age, architectural obstacles and post-operative care can become selectively more lax.

Journal Article↗

Presence of receptors for bombesin/gastrin-releasing peptide and mRNA for three receptor subtypes in human prostate cancers.

BACKGROUND: Bombesin-like peptides can function as autocrine or paracrine growth factors and stimulate the growth of some cancer cells, including human prostate cancer. Three bombesin receptor subtypes, termed gastrin-releasing peptide receptor (GRPR), neuromedin B receptor (NMBR), and bombesin receptor subtype 3 (BRS-3), have been identified in rodents and humans. METHODS: We investigated the presence and characteristics of the functional receptors for bombesin/GRP in human prostate adenocarcinoma specimens by radio-receptor assay and the mRNA expression of the three bombesin receptor subtypes by RT-PCR. RESULTS: Of the 80 specimens of primary prostate cancer examined by receptor binding assays, 50 ( approximately 63%) showed high-affinity, low-capacity binding sites for bombesin/GRP, and 12 of these 50 receptor-positive specimens also showed a second binding site. Of the 22 prostate cancer specimens analyzed by RT-PCR, 20 (91%) expressed GRPR mRNA, 3 (14%) showed NMBR mRNA, and 2 ( approximately 9%) revealed BRS-3 mRNA. No correlation was observed between receptor expression and patients' age or pathological data. CONCLUSIONS: The detection of a wide distribution of bombesin/GRP receptors in human prostate carcinomas supports the view that they may be involved in modulation of tumor progression and suggests that approaches based on binding of bombesin receptor antagonists or new targeted cytotoxic bombesin analogs to prostate cancers could be considered for the therapy.

Adenocarcinoma↗

No influence of adrenergic receptor polymorphisms on schizophrenia and antipsychotic response.

The adrenergic system plays an important role in psychiatric disorders such as depression and schizophrenia. Antagonism of the adrenergic receptor subtypes alpha1A and alpha2A has been found to have an antipsychotic effect. Genetic mutations in these receptors could be related to the alterations in the adrenergic system observed in psychiatric patients and to failure to respond to drug antagonism. We have studied one polymorphism in the alpha1A-adrenergic receptor (Arg492Cys) and two polymorphisms in the promoter region of the alpha2A-adrenergic receptor (-1291-C/G and -261-G/A) in a sample of clozapine-treated schizophrenic patients and controls. No clear differences were observed between the different groups suggesting that these polymorphisms did not play an important role in the aetiology of the disorder or in determining antipsychotic response.

Amino Acid Substitution↗

Noninherited maternal antigens do not play a role in rheumatoid arthritis susceptibility in Europe. European Consortium on Rheumatoid Arthritis Families.

OBJECTIVE: It has been proposed that noninherited maternal antigens (NIMA) (HLA-DR antigens) might play a role in susceptibility to rheumatoid arthritis (RA), especially in patients who are not genetically predisposed, such as those who are HLA-DR4 and/or shared epitope (SE) negative. The present study was undertaken to test the NIMA hypothesis in a large cohort of European RA patients assembled by the European Consortium on RA Families (ECRAF). METHODS: HLA-DRB1 oligotyping was performed in families of European RA patients for whom both parents were alive. These families were consecutively recruited by the ECRAF between 1996 and 1998, for association studies. The frequencies of HLA-DR NIMA were compared with those of the noninherited paternal antigens (NIPA) after stratification for HLA-DR*04, *0401 and/or *0404, and SE status. NIMA or NIPA that coincided with inherited HLA-DR antigens were considered redundant and excluded from analysis. Calculations concerning the whole group and restricted to patients lacking parental RA were performed. RESULTS: One hundred seventy families from France (n = 81), Belgium (n = 23), Spain (n = 24), Italy (n = 19), Portugal (n = 14), and The Netherlands (n = 9) were oligotyped. The group of probands was predominantly female (88%), positive for rheumatoid factor, DR*04, and SE (71%, 58%, and 75%, respectively), and had erosive disease (75%). Parental RA was reported in 21 families. Using the NIPA as control, the frequency of HLA-DRB1*04, *0401 and/or *0404-, or SE-positive NIMA was not found to be increased in patients lacking these susceptibility alleles. The same was true when the 21 probands with parental RA were excluded from analysis. In DRB1*04-positive patients, we found no evidence of a relevant effect of HLA-DR3 or DR6 in the NIMA. CONCLUSION: Our results do not support the notion that noninherited maternal antigens have a role in susceptibility to RA in the offspring.

Adult↗

Comparison of chromium speciation by CZE and ion exchange followed by AAS.

The hydrogen chromate anion (HCrO4-), which is the predominant species in acidic solutions and solutions with low chromium concentration, was determined by capillary zone electrophoresis (CZE) using UV detection on-column at 200 nm. A fused-silica capillary (55 cm x 50 microm i.d.) was employed with a high negative voltage of 20 kV. Total chromium was determined after reduction by H2O2 and its complexation by EDTA. The use of H2O2 as reducing agent is advantageous, as it does not increase the conductivity of the solution. Detection limits achieved (for 200 s injection time) were 30 and 8 microg/L for Cr(VI) and Cr(III), respectively. The CZE results obtained for Cr(III) and Cr(VI) were compared with those obtained by ion exchange with subsequent AAS.

Journal Article↗

Ultrastructural study of acrosome formation in mongolian gerbil (Meriones unguiculatus).

Spermatogenesis is a complex and very well organized process lasting from 30 to 75 days in mammals. The spermatogenic process has been described mainly in laboratory mammals, such as the rat, while correspondent studies in wild animals are scarce. The gerbil (Meriones unguiculatus) is a small rodent native of the arid regions of Mongolia and China. Few reports are available on reproduction in the male Mongolian gerbil. The present study provides the first description of the ultrastructural alterations in spermatid cytoplasm and nucleus, with particular reference to acrosome formation in gerbils. The testes were processed by conventional transmission electron microscopy technique. Based on the development of the acrosomal system and changes in nuclear morphology, the transformation of spermatids in spermatozoon was divided into 15 steps. There were four phases in the spermiogenesis process in the gerbil: Golgi, cap, acrosomal and maturation phases. This provides the foundation for a variety of future studies of the spermiogenesis of this animal.

Acrosome↗

[High carcinoembryonic antigen level following cancer surgery: another way to detect thyroid medullary carcinoma].

INTRODUCTION: Thyroid medullary carcinoma is usually detected in the presence of an isolated thyroid nodule or in the context of a family disease: familial thyroid medullary carcinoma or multiple endocrine neoplasia type 2A. EXEGESIS: Here we report a third means of detection: an unexplained rise in carcinoembryonic antigen levels after cancer surgery. In each case, the carcinoembryonic antigen increase led to the assessment of the caicitonin plasma level and to a thyroid echography being performed. Thyroid medullary carcinoma was confirmed in every case after surgery. CONCLUSION: Even though the association of thyroid follicular carcinoma with familial adenomatous polyposis is common, the association of thyroid medullary carcinoma with breast or colonic carcinoma remains exceptional and probably accidental. Due to the seriousness of the thyroid medullary carcinoma, it is mandatory to look for it in the event of an unexplained rise in the carcinoembryonic antigen level, by assessing the calcitonin plasma level.

Adenocarcinoma↗

Short regimen of praziquantel in the treatment of single brain enhancing lesions.

Twenty-six patients with single enhancing brain lesion (SEL) were openly assigned to receive single-day praziquantel therapy (n=14), or not (n=12). From 14 treated patients, complete resolution was found in 11, partial resolution in two, and the remaining case was later diagnosed as an arteriovenous malformation. Side effects presented in only one patient and remitted in the same day with symptomatic treatment. Conversely, the lesions persisted unchanged in six of 12 patients in the non-treatment group. Untreated patients with persisting lesions were prescribed praziquantel treatment. After this, SELs disappeared in three cases, other diagnoses (brain tuberculoma and arteriovenous malformation) were made in two, and one was not evaluated. When analyzed in regard to the baseline serology, resolution of lesions on computed tomography was found in 13 (complete=12, partial=1) of 14 seropositive patients, whereas it only happened in six (complete=5, partial=1) of 12 seronegative patients. Serological screening defines a subset of SEL patients with good prognosis. If antiparasitic therapy is to be used in patients with SEL, and we cannot find a strong argument against it, single-day praziquantel is the regimen of choice based on duration, costs, and minimal side effects.

Adolescent↗

Lumbar transplant of neurons genetically modified to secrete brain-derived neurotrophic factor attenuates allodynia and hyperalgesia after sciatic nerve constriction.

Chronic delivery of anti-nociceptive molecules by means of cell grafts near the pain processing centers of the spinal cord is a newly developing technique for the treatment of neuropathic pain. The rat neuronal cell line, RN33B, derived from E13 rat brainstem raphe and immortalized with the SV40 temperature-sensitive allele of large T antigen (tsTag), was transfected with rat brain-derived neurotrophic factor cDNA (BDNF), and the BDNF-synthesizing cell line, 33BDNF.4, was isolated. The 33BDNF.4 cells synthesized mature BDNF protein at permissive temperature (33 degrees C), when the cells were proliferating, and during differentiation at non-permissive temperature (39 degrees C) in vitro. The bio-active BDNF protein was also secreted by the cells during both growth conditions, as measured by ELISA analysis of BDNF content and secretion. The bio-activity of the BDNF in 33BDNF.4 cell conditioned media was assessed by neurite outgrowth from E15 dorsal root ganglion (DRG) cultures. A control cell line, 33V1, transfected with the vector alone, did not synthesize or secrete any significant BDNF at either growth condition. Both cell lines were used as grafts in a model of chronic neuropathic pain induced by unilateral chronic constriction injury (CCI) of the sciatic nerve. Pain-related behaviors, including cold and tactile allodynia and thermal and tactile hyperalgesia, were evaluated after CCI in the affected hindpaw. When 33BDNF.4 and 33V1 cells were transplanted in the lumbar subarachnoid space of the spinal cord 1 week after CCI, they survived greater than 7 weeks on the pia mater around the spinal cord and the 33BDNF.4 cells continued to synthesize BDNF in vivo. Furthermore, the tactile and cold allodynia and tactile and thermal hyperalgesia induced by CCI was significantly reduced during the 2-7 week period after grafts of 33BDNF.4 cells. The maximal effect on chronic pain behaviors with the BDNF grafts occurred 2-3 weeks after transplant and the anti-nociceptive effects of the BDNF cell grafts was permanent. Transplants of the control 33V1 cells had no effect on the allodynia and hyperalgesia induced by CCI and these cells did not synthesize BDNF in vivo. These data suggest that a chronically applied, low local dose of BDNF supplied by transplanted cells near the spinal dorsal horn was able to reverse the development of chronic neuropathic pain following CCI. The use of neural cell lines that are able to deliver anti-nociceptive molecules, such as BDNF, in a model of chronic pain offers a novel approach to pain management and such 'biologic minipumps' can be developed for safe use in humans.

Animals↗

c-fos expression, behavioural, endocrine and autonomic responses to acute social stress in male rats after chronic restraint: modulation by serotonin.

The effects in male rats of serotonin depletion (using the neurotoxin 5,7-dihydroxytryptamine) on the cross-sensitization of an acute social stress (defeat by a larger resident male) by previous repeated restraint stress (10 days, 60 min per day) was studied. Previous restraint increased freezing responses during social defeat in sham-operated rats, but this was not observed in those with depleted serotonin (83% or more in different regions of the brain). In contrast, neither heart rate (tachycardia) nor core temperature responses (hyperthermia) were accentuated in previously restrained rats (i.e. neither showed heterotypical sensitization), and neither adapted to repeated restraint (there is a hypothermic core temperature response during restraint). Corticosterone levels, which did adapt, nevertheless did not show accentuated responses to social defeat in previously restrained rats, though samples could only be taken 60 min after defeat. c-fos expression in the central nucleus of the amygdala 60 min after social defeat was increased by previous restraint. No other areas examined in the hypothalamus (e.g., paraventricular nucleus) or brainstem (e.g., solitary nucleus) showed differences related to previous restraint. Serotonin depletion reduced the expression of c-fos in the frontal cortex, lateral preoptic area, medial amygdala, central gray, medial and dorsal raphe, and locus coeruleus after social stress, but this was not altered by previous restraint. These results show that serotonin depletion has selective effects on the cross-sensitization of responses in previously stressed rats to a heterotypical stressor.

5,7-Dihydroxytryptamine↗

Survey of moonlighting practices and work requirements of emergency medicine residents.

We conducted an anonymous moonlighting and academic practice survey of all emergency medicine residents enrolled in accredited programs during 1997. Expanding on previous work, this survey included specific details and practice trends of moonlighting emergency medicine residents and for comparison also included academic work requirements. The typical emergency residency program requires residents to work 204 hours monthly. However, the range of required work-hours is strikingly large (120-300). Half of emergency medicine residents moonlight. The typical moonlighting resident works as a solo emergency department practitioner in multiple facilities outside of residency-affiliated institutions. Moonlighting salaries generally double a resident's annual income and are used to pay off student loans and other debt. Residents with higher student debt are more likely to moonlight. Despite the fact that most residency programs restrict moonlighting, a majority of moonlighting residents have violated an Accreditation Council for Graduate Medical Education prohibition restricting work within one period of a regular residency-scheduled shift. Half of all residents surveyed, whether involved in moonlighting practice or not, would violate a ban on the practice. Residents universally felt that moonlighting enhanced residency performance and was a positive educational experience. Use of these data may aid in the development of formal guidelines regarding emergency medicine moonlighting practice.

Accreditation↗

The prevalence of Helicobacter pylori: are emergency medicine residents at risk?.

Helicobacter pylori is strongly associated with peptic ulcer disease and gastric cancer. It is a cause of chronic active gastritis. Our hypothesis was that Emergency Physicians might be at increased risk for infection due to their exposure to gastric contents from procedures performed in the Emergency Department. Our goal was to test a group of Emergency Physicians for H. pylori infection. In this cross sectional study, we tested a group of volunteers from an Emergency Medicine residency program for H. pylori infection by serum analysis for IgG. A matched control group was also tested. Forty-five subjects were enrolled; one subject's sample was lost. Three of 44 subjects (6.8%) were positive for H. pylori antibodies. Seven of 44 controls (15.9%) tested positive. Thus, Emergency Physicians do not have increased H. pylori infection rates and may be at less risk than the general population. Routine testing is not recommended.

Adult↗

Response to criticisms of the US FDA parametric approach for withdrawal time estimation: rebuttal and comparison to the nonparametric method proposed by Concordet and Toutain.

The benefits and drawbacks of using nonparametric methods for estimating product withdrawal times have been debated for many years. This issue was recently revived by Concordet & Toutain (1997a, b) when they described a nonparametric method for withdrawal time estimation. The authors urged the international adoption of this approach, basing their recommendation on three fundamental concerns: (1) the lack of a consistent official procedure for determining a withdrawal time within the European Union (EU); (2) the need to identify a statistical method for improving the international harmonization of withdrawal times for new chemical entities; and (3) a lack of confidence in the robustness of the US Food and Drug Administration/Center for Veterinary Medicine (US FDA) procedure, particularly with respect to minor violations in the underlying parametric assumptions. Due to the critical nature of these issues, the US FDA considers it vital to respond to these concerns. This paper provides a description of the US FDA parametric procedure. We also examine the statistical concerns expressed by Concordet and Toutain, identifying the reasons for our confidence in the US FDA parametric approach. Finally, using their Monte Carlo simulation models, we generate additional datasets to explore the behaviour of their nonparametric procedure and evaluate its ability to support US FDA regulatory activities.

Animal Diseases↗