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Biomedical subjects

A Marquez

Publications and source records attributed to A Marquez.

At least 19 recordsLinked to original sources
PubMed2001

Adjuvant anthracycline therapy as a prognostic factor in metastatic breast cancer.

BACKGROUND: Prognostic factors in metastatic breast cancer continue to be identified. Previous adjuvant chemotherapy appeared to have poor prognosis in some studies but, despite this, the prior use of anthracyclines in the adjuvant setting has not been clearly established as an adverse prognostic factor once metastatic disease develops. PATIENTS AND METHODS: Patients (n = 1,436) with stages I-IIIa breast cancer were surgically treated with/without radiotherapy and/or systemic adjuvant treatment. Of these, 297 patients who relapsed with metastatic disease constitute the sample population of this retrospective study. Survival, as a function of time since diagnosis of metastatic disease, was assessed in relation to the following factors: age, size of the primary tumor, grade, number of positive axillary nodes, type of surgery, type of adjuvant treatment administered, time to relapse, number of metastatic sites, presence of visceral metastases and type of treatment employed at the time of relapse. RESULTS: In multivariable analysis three factors remained significant predictors of short survival time: more than 1 site of metastases (p = 0.00003), shorter time to relapse (p = 0.003) and the previous administration of anthracyclines as adjuvant therapy (p = 0.005). CONCLUSIONS: The prior use of adjuvant anthracyclines, with other known clinical prognostic factors, confers a poorer outcome in metastatic disease, perhaps as a result of resistant clones selection or by induction of de novo resistance.

Antibiotics, Antineoplastic↗
PubMed2001

Computerized decision support for mechanical ventilation of trauma induced ARDS: results of a randomized clinical trial.

BACKGROUND: Variability and logistic complexity of mechanical ventilatory support of acute respiratory distress syndrome, and need to standardize care among all clinicians and patients, led University of Utah/LDS Hospital physicians, nurses, and engineers to develop a comprehensive computerized protocol. This bedside decision support system was the basis of a multicenter clinical trial (1993-1998) that showed ability to export a computerized protocol to other sites and improved efficacy with computer- versus physician-directed ventilatory support. The Memorial Hermann Hospital Shock Trauma intensive care unit (ICU) (Houston, TX; a Level I trauma center and teaching affiliate of The University of Texas Houston Medical School) served as one of the 10 trial sites and recruited two thirds of the trauma patients. Results from the trauma patient subgroup at this site are reported to answer three questions: Can a computerized protocol be successfully exported to a trauma ICU? Was ventilator management different between study groups? Was patient outcome affected? METHODS: Sixty-seven trauma patients were randomized at the Memorial Hermann Shock Trauma ICU site. "Protocol" assigned patients had ventilatory support directed by the bedside respiratory therapist using the computerized protocol. "Nonprotocol" patients were managed by physician orders. RESULTS: Of the 67 trauma patients randomized, 33 were protocol (age 40 +/- 3; Injury Severity Score [ISS] 26 +/- 3; 73% blunt) and 34 were nonprotocol (age 38 +/- 2; ISS 25 +/- 2; 76% blunt). For the protocol group, the computerized protocol was used 96% of the time of ventilatory support and 95% of computer-generated instructions were followed by the bedside respiratory therapist. Outcome measures (i.e., survival, ICU length of stay, morbidity, and barotrauma) were not significantly different between groups. Fio2 > or = 0.6 and Pplateau > or = 35 cm H2O exposures were less for the protocol group. CONCLUSION: A computerized protocol for bedside decision support was successfully exported to a trauma center, and effectively standardized mechanical ventilatory support of trauma-induced acute respiratory distress syndrome without adverse effect on patient outcome.

Adult↗
PubMed2000

A DFT theoretical analysis of aldehyde condensation pathways onto methyllithium, lithium dimethylamide, and their aggregates

A DFT analysis of the condensation of monomeric methyllithium and lithium dimethylamide (LMA), as well as their homo and hetero dimers, on formaldehyde and acetaldehyde is reported. A stable complex, exhibiting a directional interaction between a lone pair of the oxygen on the aldehyde and a lithium, is first found. At this stage, the aldehyde carbonyl and the Li-X (X = C or N) bonds lie in the same plane. To proceed, the condensation reaction has to go through a transition state that mainly consists of a rotation of the aldehyde plane, placing it perpendicular to the C-C or C-N forming bond. The reaction then leads, in a strongly exothermic final step, to the addition product that is a lithium alcoholate or alpha-amino alcoholate, associating into an hetero-aggregate with the remaining moiety of the initial dimer. From the relative heights of the activation barriers, it appears that, for the heterodimer MeLi-LMA, the formation of the C-N bond should be kinetically favored over the C-C one, while the lithium ethylate resulting from the C-C binding is the thermodynamic product. A decomposition of the activation energy barriers has been carried out in order to determine the physicochemical forces responsible for the variation of the condensation activation barriers with the structure of the final species formed. The results obtained are discussed in relation with corresponding experimental data.

Journal Article↗
PubMed2000

Blunt trauma resuscitation: the old can respond.

HYPOTHESIS: Old and young trauma patients are capable of hyperdynamic response during standardized shock resuscitation. DESIGN: The responses of old and young trauma patients resuscitated using a standardized protocol are compared in an inception cohort study. A standardized resuscitation protocol was used to attain and maintain an oxygen delivery index of 600 mL/min x m2 or greater (DO2I > or = 600) for the first 24 hours in the intensive care unit. Interventions, responses, and outcomes for old (> or = 65 years) and young (<65 years) patients are described. Data were analyzed using analysis of variance, the chi2 test, and the t test; P<.05 was considered significant. SETTING: A 20-bed shock trauma intensive care unit in a regional level I trauma center. PATIENTS: Patients at high risk of postinjury multiple organ failure, ie, major organ or vascular injury and/or skeletal fractures, initial base deficit of 6 mEq/L or greater, need for 6 units or more of packed red blood cells in the first 12 hours, or age of 65 years or older with any 2 previous criteria. INTERVENTIONS: Pulmonary artery catheter, crystalloid fluid infusion, packed red blood cell transfusion, and moderate inotrope support, as needed in that sequence, to attain DO2I > or = 600. MAIN OUTCOME MEASURES: Intensive care unit length of stay and survival. RESULTS: During 19 months ending June 1999, 12 old patients (58% male; age, 76 +/- 2 years [mean +/- SEM] [P<.0011; Injury Severity Score, 20 +/- 2 [P=.02]) and 54 young patients (61% male; age, 37 +/- 2 years; Injury Severity Score, 32 +/- 2) were resuscitated. Initially, for old patients (cardiac index, 2.0 +/- 0.2 L/min x m2) and for young patients (cardiac index, 3.0 +/- 0.2 L/min x m2; P=.01), 24-hour volumes were as follows: 16 +/- 3 L of crystalloid and 12 +/- 3 units of packed red blood cells for the old patients and 21 +/- 2 L of crystalloid and 19 +/- 2 units of packed red blood cells for the young patients. For old patients, 9 (75%) attained DO2I > or = 600, and 11 (92%) survived 7 or more days and 5 (42%) 30 or more days. For young patients, 45 (83%) attained the DO2I goal, and 48 (89%) survived 30 or more days. Intensive care unit length of stay was 25 +/- 9 days for the old patients and 23 +/- 2 days for the young patients. CONCLUSIONS: Elderly patients have initially depressed cardiac index but generate hyperdynamic response. Although ultimate outcome is poorer than in the younger cohort, resuscitation is not futile.

Adult↗
PubMed2000

Molecular characterization of schizophrenia viewed by microarray analysis of gene expression in prefrontal cortex.

Microarray expression profiling of prefrontal cortex from matched pairs of schizophrenic and control subjects and hierarchical data analysis revealed that transcripts encoding proteins involved in the regulation of presynaptic function (PSYN) were decreased in all subjects with schizophrenia. Genes of the PSYN group showed a different combination of decreased expression across subjects. Over 250 other gene groups did not show altered expression. Selected PSYN microarray observations were verified by in situ hybridization. Two of the most consistently changed transcripts in the PSYN functional gene group, N-ethylmaleimide sensitive factor and synapsin II, were decreased in ten of ten and nine of ten subjects with schizophrenia, respectively. The combined data suggest that subjects with schizophrenia share a common abnormality in presynaptic function. We set forth a predictive, testable model.

Animals↗
PubMed2000

Chronic liver injury related to use of bentazepam: an unusual instance of benzodiazepine hepatotoxicity.

Liver injury induced by benzodiazepines is rare and is classified as an unpredictable or idiosyncratic hepatotoxic reaction. Early reports indicated that in most cases the pattern of liver injury was cholestatic. We describe three patients with persistent increases in liver transaminase levels after several weeks of treatment with bentazepam, a benzodiazepine marketed in Spain for anxiety disorders. In all cases withdrawal of the drug was followed by resolution of transaminase level abnormalities. A liver biopsy (done in one patient only) showed histological evidence of severe chronic active hepatitis. In conclusion, these findings, together with two previously published case reports, suggest that a benzodiazepine can cause chronic hepatitis and argue in favor of using liver function tests to monitor all patients taking bentazepam.

Administration, Oral↗
PubMed2000

Hepatocyte ultrastructural alterations in cocaine users.

The ultrastructural examination of liver biopsies from five male cocaine users showed hepatocytes presenting diverse alterations in rough and smooth endoplasmic reticulum, mitochondria, nuclei and microvilli. Lipid deposition and an increase of autophagic vacuoles were also observed. This study demonstrates that the hepatocyte is an important target cell for cocaine toxic effects in some patients.

Adult↗
PubMed1999

Efficacy of computerized decision support for mechanical ventilation: results of a prospective multi-center randomized trial.

200 adult respiratory distress syndrome patients were included in a prospective multicenter randomized trial to determine the efficacy of computerized decision support. The study was done in 10 medical centers across the United States. There was no significant difference in survival between the two treatment groups (mean 2 = 0.49 p = 0.49) or in ICU length of stay between the two treatment groups when controlling for survival (F(1df) = 0.88, p = 0.37.) There was a significant reduction in morbidity as measured by multi-organ dysfunction score in the protocol group (F(1df) = 4.1, p = 0.04) as well as significantly lower incidence and severity of overdistension lung injury (F(1df) = 45.2, p < 0.001). We rejected the null hypothesis. Efficacy was best for the protocol group. Protocols were used for 32,055 hours (15 staff person years, 3.7 patient years or 1335 patient days). Protocols were active 96% of the time. 38,546 instructions were generated. 94% were followed. This study indicates that care using a computerized decision support system for ventilator management can be effectively transferred to many different clinical settings and significantly improve patient morbidity.

Adult↗
PubMed1998

Ultrastructure of hepatocyte abnormalities in perimetastatic areas.

The ultrastructural pathology of non-invaded hepatocytes located in close proximity to metastases from diverse gastrointestinal carcinomas was studied. Observed abnormalities included swelling of rough and smooth endoplasmic reticulum, proliferation of lysosomes, and mitochondrial alterations as presence of granules and paracrystalline inclusions, marked pleomorphism, and lack of cristae. These results show that, contrary to the classical conception, the non-invaded cells surrounding primary tumours or their metastases could be abnormal.

Endoplasmic Reticulum, Rough↗
PubMed1997

Microvascular pathology in the skeletal muscle paraneoplastic phenomenon.

An electron microscopic investigation was made in order to study capillary alterations in the muscle paraneoplastic phenomenon associated with different malignant tumours. Several abnormalities were found including basement membrane widening and lamination, endothelial hypertrophy, a varied degree of lumen occlusion, and proliferative changes in pericytes. A degenerative process leading to capillary necrosis was also observed. A mononuclear cell infiltrate formed by macrophages, lymphocytes and mast cells was seen. The capillary changes observed suggest the existence of an autoimmune vascular factor in the etiopathogenesis of muscle damage in this phenomenon.

Capillaries↗
PubMed1996

Skeletal muscle ultrastructural pathology in Serinus canarius infected with Plasmodium cathemerium.

Serinus canarius infected with Plasmodium cathemerium was used as an animal model in order to study the skeletal muscle compromise in malaria. Pectoral muscle biopsies were obtained from 7 infected female birds. The transmission electron microscopic study showed alterations of contractile and sarcotubular systems, mitochondrial abnormalities, lysosomal proliferation and nuclear pyknosis. The sarcolemma looked disrupted and separated from the necrotic fibres. Capillary abnormalities included endothelial degeneration with proliferation of lysosomal structures, penetration of endothelial cell by the parasites and necrosis. A mononuclear cell infiltrate formed by plasmocytes, lymphocytes and macrophages was observed. This investigation shows that skeletal muscle is an important target tissue for some malaria parasites.

Animals↗
PubMed1996

Skeletal muscle pathology in mice experimentally infected with Toxoplasma gondii.

In two different groups of mice, the infection with Toxoplasma gondii was produced by intraperitoneal route, with 2 x 10(5) parasites (n = 8) and 14 x 10(5) parasites (n = 3). Five days after infection animals were killed to examine skeletal muscles by light and transmission electron microscopy. Severity of muscle alterations depended upon concentration of parasites. Parasite cysts were not identified in muscle sections. Ultrastructural features revealed different degrees of fibre atrophy, alterations in the sarcomeric structure and, in some cases, disorganization of contractile and sarcotubular systems. Changes in muscular capillaries included loss of the endothelial wall, occlusion of lumen and necrosis. Motor end-plates were abnormal and axonolysis was present. A mononuclear cell infiltrate consisted of macrophages, lymphocytes, mastocytes and eosinophils were observed. In this murine model it was demonstrated that the infection of non-immunocompromised hosts with Toxoplasma gondii produces an acute myositis.

Animals↗
PubMed1995

Toxic and neurogenic factors in chloroquine myopathy fibre selectivity.

Biopsies from soleus and extensor digitorum longus (EDL) muscles obtained in rats with an experimental chloroquine myopathy were studied ultrastructurally. Two different histopathological pictures were observed: type I fibres from soleus exhibited a vacuolar myopathy with an almost normal sarcomeric structure; type II fibres from EDL did not show vacuoles but changes similar to neurogenic atrophy. Our results suggest that chloroquine produces direct toxic effects in type I fibres and secondary neurogenic damage in type II fibres.

Animals↗
PubMed1994

Ultrastructure of systemic sclerosis inflammatory myopathy.

Muscle biopsies from 7 patients with systemic sclerosis (SS) and a slowly progressive proximal muscular weakness were studied ultrastructurally. In all cases an inflammatory myopathy was found exhibiting fibre atrophy, occasional fibre necrosis, connective tissue proliferation, filamentous bodies, concentric laminated bodies and a mononuclear cell infiltration formed by lymphocytes, macrophages and mast cells. Capillary abnormalities included alterations of endothelium, thickening and reduplication of basement membrane and the presence of cylindric confronting cisternae. The different associations between muscle diseases and SS are grouped. Our data suggest that SS inflammatory myopathy is a distinct clinical and pathological entity.

Biopsy↗
PubMed1993

High lipoprotein(a) in children from kindreds with parental premature myocardial infarction.

In 98 children from 98 kindreds, 49 with and 49 without parental premature myocardial infarction (age < or = 45 y), our specific aim was to determine whether, and to what degree, lipoprotein(a) [Lp(a)] and other atherogenic lipids and lipoproteins might be overexpressed in children from premature infarction kindreds. Median Lp(a) (270 mg/L) in case boys was nearly twice that in control boys (140 mg/L) (p < or = 0.001). In a logistic regression model including age, Quetelet index (relative ponderosity), Lp(a), apo A1, apo B, triglyceride, and pubertal status, the 24 case boys had higher Lp(a) (p = 0.03), higher triglyceride (p = 0.036), and marginally lower apo A1 (p = 0.06) than the 26 control boys. Median Lp(a) in case girls (200 mg/L) was much higher than in control girls (150 mg/L) (p < or = 0.01). In a logistic regression model including age, Quetelet index, Lp(a), apo A1, apo B, triglyceride, and menarchal status, Lp(a) was higher (p = 0.02), apo B was marginally higher (p = 0.07), and apo A1 was lower (p = 0.008) in 25 case girls than in 23 control girls. Reflecting familial clustering of major lipid-lipoprotein risk factors for coronary heart disease, children from kindreds with premature parental myocardial infarction were distinguished from children from control kindreds by high Lp(a) and also had higher apo B and triglyceride and lower apo A1 levels.

Adolescent↗
PubMed1990

Molecular analysis of barley mutants deficient in chloroplast glutamine synthetase.

A barley leaf cDNA library has been screened with two oligonucleotide probes designed to hybridize to conserved sequences in glutamine synthetase (GS) genes from higher plants. Two GS cDNA clones were identified as hybridizing strongly to one or both probes. The larger clone (pcHvGS6) contained a 1.6 kb insert which was shown by primer extension analysis to be an almost full-length cDNA. Both clones were more closely related to cDNAs for the chloroplast form of GS (GS2) from pea and Phaseolus vulgaris than to cDNAs for the cytosolic form (GS1). A sequence identical to an N-terminal sequence determined from a purified preparation of the mature GS2 polypeptide (NH2-XLGPETTGVIQRMQQ) was found in the pcHvGS6-encoded polypeptide at residues 46-61, indicating a pre-sequence of at least 45 amino acids. The pre-sequence has only limited sequence homology to the pre-sequences of pea and P. vulgaris GS2 subunits, but is similarly rich in basic residues and possesses some of the structural features common to the targeting sequences of other chloroplast proteins. The molecular lesions responsible for the GS2-deficient phenotypes of eight photorespiratory mutants of barley were investigated using a gene-specific probe from pcHvGS6 to assay for GS2 mRNA, and an anti-GS antiserum to assay for GS2 protein. Three classes of mutants were identified: class I, in which absence of cross-reacting material was correlated with low or undetectable levels of GS2 mRNA; class II, which had normal or increased levels of GS2 mRNA but very little GS2 protein; and class III, which had significant amounts of GS2 protein but little or no GS2 activity.

Amino Acid Sequence↗