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Biomedical subjects

J M Sanchez

Publications and source records attributed to J M Sanchez.

At least 19 recordsLinked to original sources
PubMed2002

Phase I study of weekly CPT-11 (irinotecan)/docetaxel in patients with advanced solid tumors.

Based on the synergistic cytotoxicity demonstrated in vitro by topoisomerase I inhibitors followed by docetaxel and the feasibility of giving both drugs on a weekly schedule avoiding overlapping toxicities, we designed a phase I trial of weekly CPT-11 (irinotecan)/docetaxel to determine the dose-limiting toxicities (DLT) and the maximum-tolerated dose (MTD) of this combination. Eighteen patients with advanced solid tumors treated with at least one prior chemotherapy regimen were included in this trial. CPT-11 was administered as a 90-min (intravenous) IV infusion followed immediately by docetaxel as a 30-min IV infusion. Both drugs were given on days 1, 8 and 15 in 4-week cycles. Four escalating dose levels of CPT-11/docetaxel (level I: 60/20 mg/m(2), level II: 60/25 mg/m(2), level III: 70/25 mg/m(2), and level IV: 70/30 mg/m(2)) were studied. Forty-seven cycles were administered (range, 1-5 courses) with a median number of 2.6 cycles per patient. Grade 4 leukopenia was the DLT reached at dose-level IV (CPT-11/docetaxel 70/30 mg/m(2)). Four patients had grade 3 anemia at dose levels III (two patients) and IV (two patients), while grade 3/4 thrombocytopenia was not seen. Grade 3/4 non-hematologic toxicities included grade 3 diarrhea in two patients (dose levels II and IV), grade 3 asthenia in one patient (dose level II) and grade 3 stomatitis in one patient (dose level I). The recommended dose of this weekly schedule is CPT-11 70 mg/m(2) and docetaxel 25 mg/m(2). DLT of this regimen is leukopenia, although toxicity is manageable at the recommended dose level. The activity of this regimen is being evaluated in a phase II study in previously treated patients with advanced non-small cell lung cancer.

Adult↗
PubMed2001

Spontaneous L1(2) order at Ni(90)Al(10)(110) surfaces: an x-ray and first-principles-calculation study.

We have combined x-ray diffraction studies with first-principles calculations to study the interplay between segregation and ordering at the (110) surface of Ni(90)Al(10). We find a L1(2)-ordered monolayer at the surface. The observed ordering as well as recently reported Al segregation at the surface are explained in a consistent picture. A delicate competition between the tendency for Al segregation and ordering in the Ni-Al system induced by the symmetry break at the surface stabilizes a long-range ordered surface in the entire concentration range c(Ni)>0.75.

Journal Article↗
PubMed2001

Withdrawing and withholding life support in the intensive care unit: a Spanish prospective multi-centre observational study.

OBJECTIVE: To determine how frequently life support is withheld or withdrawn from adult critically ill patients, and how physicians and patients families agree on the decision regarding the limitation of life support. DESIGN: Prospective multi-centre cohort study. SETTING: Six adult medical-surgical Spanish intensive care units (ICUs). PATIENTS AND PARTICIPANTS: Three thousand four hundred ninety-eight consecutive patients admitted to six ICUs were enrolled. MEASUREMENTS AND RESULTS: Data collected included age, sex, SAPS II score on admission and within 24 h of the decision to limit treatment, length of ICU stay, outcome at ICU discharge, cause and mode of death, time to death after the decision to withhold or withdraw life support, consultation and agreement with patient's family regarding withholding or withdrawal, and the modalities of therapies withdrawn or withheld. Two hundred twenty-six (6.6%) of 3,498 patients had therapy withheld or withdrawn and 221 of them died in the ICU. Age, SAPS II and length of ICU stay were significantly higher in patients dying patients who had therapy withheld or withdrawn than in patients dying despite active treatment. The proposal to withhold or withdraw life support was initiated by physicians in 210 (92.9%) of 226 patients and by the family in the remaining cases. The patient's family was not involved in the decision to withhold or withdraw life support therapy in 64 (28.3%) of 226 cases. Only 21 (9%) patients had expressed their wish to decline life-prolonging therapy prior to ICU admission. CONCLUSIONS: The withholding and withdrawing of treatment was frequent in critically ill patients and was initiated primarily by physicians.

Adult↗
PubMed2001

Coronavirus derived expression systems.

Both helper dependent expression systems, based on two components, and single genomes constructed by targeted recombination, or by using infectious cDNA clones, have been developed. The sequences that regulate transcription have been characterized mainly using helper dependent expression systems and it will now be possible to validate them using single genomes. The genome of coronaviruses has been engineered by modification of the infectious cDNA leading to an efficient (>20 microg ml(-1)) and stable (>20 passages) expression of the foreign gene. The possibility of engineering the tissue and species tropism to target expression to different organs and animal species, including humans, increases the potential of coronaviruses as vectors. Thus, coronaviruses are promising virus vectors for vaccine development and, possibly, for gene therapy.

Coronavirus↗
PubMed2001

The role of chemotherapy in early non-small-cell lung cancer management.

Great advances have been made in chemotherapy in advanced and metastatic non-small-cell lung cancer (NSCLC), and a major milestone was reached with the administration of neoadjuvant chemotherapy in stage IIIA N2 disease. The systemic nature of lung cancer has been confirmed by many genetic analyses documenting micrometastases in negative lymph nodes and bone marrow, and mRNA gene overexpression as a surrogate of cancer cells has been identified in peripheral blood. Furthermore, serum or plasma cell-free tumor DNA has been observed even in tumors with a diameter of less than 2 cm. Pharmacogenetic screening can lead to tailored chemotherapy even in patients with early disease through the use of a genetic tool kit that will allow us to optimize the use of chemotherapy by using serial measurements of serum DNA that can help to detect residual disease and re-assess the chemosensitivity of sub-clinical micrometastatic disease. The ongoing (neo)adjuvant taxol/carboplatin hope (NATCH) trial is testing the value of three cycles of chemotherapy given pre- or post-operatively compared with surgery alone and will analyze genetic abnormalities in serum DNA at three different points during patient follow-up. Our major concern in this review is to analyze the pros and cons of chemotherapy in NSCLC. Although this review is not a formal meta-analysis, we have discussed the most relevant published studies in this field. We conclude that not only is there no evidence of detrimental effects of chemotherapy, in fact, there are many indications that chemotherapy induces response in up to 80% of patients and downgrades N2 disease in up to 50% of patients. This translates into significantly better survival when accompanied by complete resection. Since at least 50% of patients with stage IB disease develop distant metastases, it seems logical to explore the role of chemotherapy in early disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Increased nitric oxide synthase activity and expression in the human uterine artery during pregnancy.

Evidence exists that NO plays a role in the vasodilation that occurs during pregnancy. The purpose of the present study was to determine whether the role of NO is associated with an increase in the activity and protein expression of NO synthase (NOS) in the human uterine artery. Uterine arteries were obtained from pregnant patients (P arteries) and nonpregnant patients (NP arteries). NOS activity was estimated with the L-[(3)H]-arginine-to-L-[(3)H]-citrulline conversion method and on the basis of changes in tissue levels of cGMP. Western immunoblotting and immunohistochemistry were used to assess NOS protein expression. Ca(2+)-dependent NOS activity was 8 times greater (P:<0.01) in P than in NP arteries. Although most of this pregnancy-induced increase in NOS activity was Ca(2+) dependent (64%), a considerable portion was Ca(2+) independent. Expressions of endothelial NOS (eNOS) and neuronal NOS, but not inducible NOS, were demonstrated in P and NP arteries. The eNOS was located in the endothelium and stained with a qualitative order of P arteries>NP arteries (follicular)>NP arteries (luteal). The neuronal NOS was located in the adventitia of P and NP arteries. Basal NO-dependent and bradykinin-stimulated levels of cGMP were higher (P:<0.05) in P than in NP arteries. These results indicate that an upregulation of eNOS protein expression could account for the increased NO synthesis/release in the human uterine artery during pregnancy.

Adult↗
PubMed1999

Air pollution and health effects: A study of medical visits among children in Santiago, Chile.

Many epidemiological studies conducted in the last several years have reported associations between exposure to airborne particulate matter, measured as PM10 (<10 microm in diameter), and daily morbidity and mortality. However, much of the evidence involves effects on the elderly population; there is less evidence about the effects of particulates on children, especially those under 2 years of age. To examine these issues, we conducted time-series analyses of 2 years of daily visits to primary health care clinics in Santiago, Chile, where counts were computed for either upper or lower respiratory symptoms and for cohorts of children 3-15 years of age and below age 2. Daily PM10 and ozone measurements and meteorological variables were available from instruments located in downtown Santiago. The multiple regression analysis indicates a statistically significant association between PM10 and medical visits for lower respiratory symptoms in children ages 3-15 and in children under age 2. PM10 is also associated with medical visits related to upper respiratory symptoms in the older cohort, while ozone is associated with visits related to both lower and upper respiratory symptoms in the older cohort. For children under age 2, a 50- microg/m3 change in PM10 (the approximate interquartile range) is associated with a 4-12% increase in lower respiratory symptoms. For children 3-15 years of age, the increase in lower respiratory symptoms ranges from 3 to 9% for a 50- microg/m3 change in PM10 and 5% per 50 ppb change in ozone. These magnitudes are similar to results from studies of children undertaken in Western industrial nations.

Adolescent↗
PubMed1997

Atypical carcinoid of larynx: presentation with scalp metastases.

A case of atypical carcinoid tumour of the larynx in a 72-year-old woman is presented. The neoplasm was located in the supraglottic region and was first manifest by metastases to the scalp. The presence of amyloid-like material and calcitonin-positive cells were features that resembled medullary carcinoma of the thyroid. Clinically, it pursued an aggressive course that led to death 58 months after diagnosis. The literature is reviewed, particularly that regarding the differential diagnosis.

Aged↗
PubMed1997

SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients.

The authors analyzed the incidence of sexual dysfunction (SD) with different selective serotonin reuptake inhibitors (SSRIs; fluoxetine, fluvoxamine, paroxetine, and sertraline) and hence the qualitative and quantitative changes in SD throughout time in a prospective and multicenter study. Outpatients (192 women and 152 men; age = 39.6 +/- 11.4 years) under treatment with SSRIs were interviewed with an SD questionnaire designed for this purpose by the authors and that included questions about the following: decreased libido, delayed orgasm or anorgasmia, delayed ejaculation, inability to ejaculate, impotence, and general sexual satisfaction. Patients with the following criteria were included: normal sexual function before SSRI intake, exclusive treatment with SSRIs or treatment associated with benzodiazepines, previous heterosexual or self-erotic current sexual practices. Excluded were patients with previous sexual dysfunction, association of SSRIs with neuroleptics, recent hormone intake, and significant medical illnesses. There was a significant increase in the incidence of SD when physicians asked the patients direct questions (58%) versus when SD was spontaneously reported (14%). There were some significant differences among different SSRIs: paroxetine provoked more delay of orgasm or ejaculation and more impotence than fluvoxamine, fluoxetine and sertraline (chi 2, p < .05). Only 24.5% of the patients had a good tolerance of their sexual dysfunction. Twelve male patients who suffered from premature ejaculation before the treatment preferred to maintain delayed ejaculation, and their sexual satisfaction, and that of their partners, clearly improved. Sexual dysfunction was positively correlated with dose. Patients experienced substantial improvement in sexual function when the dose was diminished or the drug was withdrawn. Men showed more incidence of sexual dysfunction than women, but women's sexual dysfunction was more intense than men's. In only 5.8% of patients, the dysfunction disappeared completely within 6 months, but 81.4% showed no improvement at all by the end of this period. Twelve of 15 patients experienced total improvement when the treatment was changed to moclobemide (450-600 mg/day), and 3 of 5 patients improved when treatment was changed to amineptine (200 mg/day).

1-Naphthylamine↗
PubMed1997

Variabilin: a dual inhibitor of human secretory and cytosolic phospholipase A2 with anti-inflammatory activity.

The marine product variabilin was identified as a novel inhibitor of phospholipase A2 (PLA2), which exhibited IC50 values of 6.9 microM and 7.9 microM for human synovial secretory PLA2 and U937 cells cytosolic PLA2 activities, respectively. This compound was less potent on bee venom or zymosan-injected rat air pouch enzymes and failed to affect Naja naja venom PLA2. The production of leukotriene B4 by human neutrophils stimulated with calcium ionophore A23187 was also inhibited by variabilin, which was without effect on 5-lipoxygenase, cyclo-oxygenase 1 and cyclo-oxygenase 2 activities in cell-free assays. Other functions of human neutrophils, such as degranulation and superoxide generation, were also significantly reduced in vitro. Variabilin administered topically suppressed the mouse ear edema induced by 12-O-tetradecanoylphorbol 13-acetate, whereas the ear edema induced by arachidonic acid was unaffected; this suggests an action previous to arachidonic acid metabolism. This compound administered p.o. at 30 mg/kg and 45 mg/kg significantly inhibited mouse paw edema induced by carrageenan and, at 0.01 to 1.0 micromol/pouch in the mouse air pouch injected with zymosan, exerted a marked inhibition on PGE2 and leukotriene B4 levels in exudates (ID50 values of approximately 0.028-0.029 micromol/pouch), without affecting cell migration. Our results indicate that variabilin is an inhibitor of human secretory and cytosolic PLA2 activities that controls eicosanoid production in vitro and in vivo, inhibits neutrophil degranulation and superoxide generation in vitro and shows anti-inflammatory activity after topical or p.o. administration to mice.

Animals↗
PubMed1996

Nitrogen metabolite signalling involves the C-terminus and the GATA domain of the Aspergillus transcription factor AREA and the 3' untranslated region of its mRNA.

AREA is a GATA transcription factor which mediates nitrogen metabolite repression in Aspergillus nidulans in response to intracellular glutamine levels. We have identified and localized three elements important to modulation of AREA function: a region of 13 residues within the DNA-binding GATA domain which forms a putative extended loop structure, the 12 C-terminal residues, and sequences within a 218 nucleotide region of the 3' UTR. The 12 C-terminal residues are also required for transcriptional activation at a subset of loci under areA control. Specific deletions within the 3' UTR and the C-terminus cause similar levels of derepression and the mutations are additive, implicating two principal signal transduction pathways. The contribution of the 3' UTR to AREA modulation is effected at the level of transcript stability such that the areA mRNA is at least five times more stable under nitrogen-derepressing conditions than it is under repressing growth conditions.

Amino Acid Sequence↗
PubMed1994

Basaloid-squamous cell carcinoma of the larynx and hypopharynx. A clinicopathologic study of 7 cases.

During a 16-year period (1974-1989), a retrospective review of 468 surgical specimens of laryngectomy yielded 7 cases (0.66%) of basaloid-squamous cell carcinoma. They were all males between 42 and 63 years of age. Four cases were supraglottic and one transglottic. The other two arose in the left pyriform sinus and vallecula, respectively. At diagnostic time, 4 cases were Stage III and 2 Stage IV, only one being Stage II. Glanz index of histologic malignancy was high (> 5) in most cases (6/7). Mitotic rate was also high (22-78 mitoses/10 HPF). Lymph node metastases were documented at diagnosis in 5 cases, 3 of them presenting with extracapsular extension. One case developed liver metastases. During the follow-up, lymph nodes of the neck were again metastasized in 4 cases, and stomal recurrence was present in another one. Death of disease was confirmed in 5 cases after 10 to 35 months of follow-up. Overall survival was 28.5% after 3 years.

Adult↗
PubMed1988

Plasmids of Azotobacter vinelandii.

Four laboratory strains and two isolates of Azotobacter vinelandii were found to contain plasmids. Twenty-five laboratory strains which could fix nitrogen did not have free, covalently closed circular plasmid DNA. The plasmids varied in size from 9 to 52 megadaltons, and each strain yielded only one plasmid. No discernible differences in ability to fix nitrogen were found between plasmid-bearing and cured cultures.

Azotobacter↗
PubMed1983

Erroneous interpretation of pulmonary capillary wedge pressure in massive pulmonary embolism.

Pulmonary capillary wedge pressure (WP) values obtained after catheterization of a pulmonary artery (PA) totally occluded by thrombus may be erroneously interpreted. The left lower lobe PA was catheterized in 13 anesthetized dogs. Measurements of mean pulmonary artery pressure (MPAP) and WP were performed before and after total occlusion of the PA by a clamp located 1 cm from the tip of the catheter. There was a difference between pulmonary artery occluded pressure (PAoP), MPAP, and WP, both in normovolemic and overload conditions (p less than .01). The PAoP was not equivalent either to WP or to MPAP. In massive pulmonary embolism, WP may not reflect left ventricular end-diastolic pressure (LVEDP).

Animals↗
PubMed1981

Fetal phenotype in a case of partial trisomy 21 and partial monosomy 22 detected prenatally.

Prenatal diagnosis was performed in a woman whose previous pregnancy resulted in a girl with probable Down syndrome who died soon after delivery. The mother was found to be a carrier of a reciprocal balanced translocation between chromosomes 21 and 22, and the fetus was found to have an unbalanced translocation involving chromosomes 21 and 22: 46,XX, -22, +t(21;22)(q22;q11)(21 pter leads to 21q22::22q11 leads to 22qter). Despite partial monosomy for the proximal segment of 22 and trisomy for proximal 21, the fetus did not have gross external abnormalities, but several internal malformations were found. To our knowledge, this is the first time that this unbalanced karyotype has been described.

Abnormalities, Multiple↗