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Biomedical subjects

M Maldonado

Publications and source records attributed to M Maldonado.

At least 19 recordsLinked to original sources

P53 allelic loss and outcome in patients with squamous cell carcinoma of the head and neck.

Although loss of heterozygosity (LOH) on the p53 locus is frequent in squamous cell carcinomas of the head and neck (SCCHN), controversy still remains regarding the prognostic significance of such an event. Eighty consecutive SCCHN were studied. DNA was extracted from matched sets of normal and tumour tissue and used for polymerase chain reaction amplification of microsatellite markers located in the p53 locus. LOH at the p53 locus was found in 39 (70%) of the 56 informative cases. No relationship was found between p53 LOH and age, site, T stage, N stage, disease stage, and histological differentiation. Recurrence occurred in 53% of the cases with LOH and in 58% of the cases without it (P = 0.28). Moreover, no statistically significant association was found between p53 LOH and disease-specific survival (log-rank P = 0.98). These data suggest that although LOH at the p53 locus is common in SCCHN, this finding is of little clinical significance.

Carcinoma, Squamous Cell↗

[The role of mitral valve balloon valvuloplasty in the treatment of rheumatic mitral valve stenosis during pregnancy].

OBJECTIVE: To analyze the immediate results and the clinical evolution of a group of fertile age women with rheumatic mitral stenosis, in whom percutaneous balloon mitral valvuloplasty was performed before or during pregnancy. PATIENTS AND METHOD: Eighty-one women with mitral stenosis, submitted to balloon mitral vavuloplasty, were studied. They were divided into three groups, according to their desire of no further pregnancies (group A; n = 19), pregnancy during the follow-up (group B; n = 23) or valvuloplasty was performed during pregnancy (group C; n = 39). Patients from group B and C were controlled during pregnancy, childbirth and puerperium, and the newborns of women in group C were followed from birth to the age of 5 years. RESULTS: Mortality in the three groups was null and the incidence of miscarriage was 2 (8.6%) in group B and 3 (9.1%) in group C. Normal delivery was predominant in group B and delivery by caesarean was predominant in group B. Success was immediate in all the cases. The procedure was repeated in 3 women due to restenosis. The media valvar area rase from 0.93 to 2.05 cm2 in group A, from 1.28 to 2.04 cm2 in group B and from 0.84 to 2.14 cm2 in group C (intergroup p = NS). The functional class improved in the three groups of patients. CONCLUSION: Percutaneous balloon mitral valvuloplasty is an effective, efficient method for the treatment of rheumatic mitral stenosis during pregnancy, after organogenesis, or at any time in a woman's life, as long as it is indicated according to clinical and echocardiographic evaluation criteria.

Adult↗

Actigraphic sleep-wake patterns and urinary 6-sulfatoxymelatonin excretion in patients with Alzheimer's disease.

Recent studies suggest melatonin, due to its antioxidant and free-radical-scavenging actions, may play a role in the neuroprotection against amyloid, which is implicated in the pathogenesis of Alzheimer's disease (AD). In this study, we determined urinary 6-sulfatoxymelatonin (aMT6s) excretion together with actigraphic sleep-wake patterns of untreated male patients with AD who lived at home. Results were compared with those obtained from normal age-matched elderly and normal young male subjects. Similar measurements were also performed in another group of patients with AD who were treated with a cholinesterase inhibitor (Donepezil, Aricept). Total 24h aMT6s values were significantly reduced in elderly controls (19.9h +/- 5.2 microg/ 24h), in those with untreated AD (12.7 +/- 4.4 microg/24h), and in patients treated for AD (12.4 +/- 4.4 microg/24h) compared with normal young men (32.8 +/- 3.1 microg/24h). A day-night difference in aMT6s was evident in all young controls, in 50% of elderly controls, in only 20% of patients with untreated AD, and in 67% of those with AD receiving Aricept. Sleep quality (expressed as sleep efficiency, wake time, and long undisturbed sleep duration) was better in young and elderly controls compared with the two groups of patients with AD. There was no significant correlation between aMT6s values or sleep patterns and the severity of cognitive impairment in patients with AD. Taken together, these data suggest that disrupted sleep, decreased melatonin production, and partial lack of day-night difference in melatonin secretion were observed equally in normal elderly and in patients with AD. Our results do not permit drawing any conclusion as to whether changes in urinary aMT6s excretion is correlated with disturbed sleep in patients with AD.

Adult↗

Xanthine oxidase released from reperfused hind limbs mediate kupffer cell activation, neutrophil sequestration, and hepatic oxidative stress in rats subjected to tourniquet shock.

We have shown previously that rats subjected to tourniquet shock develop an acute form of remote organ injury of the liver that is both Kupffer cell (KC) and polymorphonuclear (PMN) leukocyte dependent. Circulating plasma xanthine oxidase (XO) has been shown to be responsible for the development of endothelial dysfunction and for remote organ injury of the lung and intestine after ischemia-reperfusion protocols. We now hypothesize that XO is released from rat hind limbs upon reperfusion and that it is responsible for KC and PMN leukocyte activation in this shock model. Our results show that about 30% of rat gastrocnemius muscle xanthine dehydrogenase (XD) is converted to XO during the 5-h tourniquet period and that it is released into the femoral vein within 10 min of reperfusion. Total muscle xanthine oxidoreductase activity (XO + XD) decreases within 30 min of reperfusion and is paralleled by a corresponding increase in femoral vein lactic dehydrogenase. In addition, liver tissue XO increases significantly within 30 min of reperfusion without a corresponding conversion of endogenous XD. Conversion of hepatic XD becomes evident 60 min after reperfusion is initiated, as does XO, and alanine aminotransferase (ALT) release into the hepatic vein, presumably from damaged hepatocytes as a consequence of oxidative stress. Tissue myeloperoxidase activity also increases significantly after the 60-min reperfusion period. That XO mediates KC and PMN activation is supported by the following observations: a) the close relationships between plasma XO and the time courses of tumor necrosis factor-alpha TNFalpha release into the hepatic vein and colloidal carbon clearance by KCs; b) that colloidal carbon clearance, TNFalpha and ALT release, loss of tissue free thiols, lipid peroxidation (TBARS), and liver infiltration by PMN neutrophils can also be induced by the administration of exogenous XO to normal rats; and c) pretreatment of rats with allopurinol inhibits KC activation and liver leukocyte infiltration. These results suggest that XO, released from the ischemic limb on reperfusion, is taken up by the liver were it mediates KC and PMN neutrophil activation and thus contributes to the development of multiple system organ failure after hind limb reperfusion.

Alanine Transaminase↗

Patient privacy.

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Confidentiality↗

Bright futures.

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Fellowships and Scholarships↗

Not for sale.

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Drug Industry↗

Getting paid.

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Academic Medical Centers↗

Induction of autoimmunity in a transgenic model of B cell receptor peripheral tolerance: changes in coreceptors and B cell receptor-induced tyrosine-phosphoproteins.

Abrogation of peripheral tolerance in transgenic mice that express a uniform B-cell receptor may create a powerful tool to examine the molecular mechanisms that underlie the autoimmune response in B cells. Here we report that processes that induce a systemic lupus erythematosus-like syndrome in normal mice, namely chronic graft vs host reaction, trigger systemic autoimmunity in a well-established transgenic mice model of B cell receptor peripheral tolerance. The induction of graft vs host reaction in mice that carry both a rearranged B cell Ag receptors specific for hen egg lysozyme and expressing chronically circulating hen egg lysozyme Ag resulted in induction of high and sustained levels of circulating anti-hen egg lysozyme autoantibodies and glomerulonephritis with proteinuria. This was associated with marked changes in expression of cell-surface proteins, such as CD23 and complement receptor 2. B cells from the graft vs host-induced mice could proliferate in vitro in response to self-Ag, and upon stimulation with anti-IgD demonstrated rapid phosphotyrosine phosphorylation of specific proteins, which could not be induced in the anergic double transgenic B cells. Conversely, loss of tolerance was not associated with a higher induction in the level of Syk kinase phosphorylation following stimulation with anti-IgD. Taken collectively, these data establish that 1) processes that induce a systemic lupus erythematosus-like syndrome in normal mice can abrogate peripheral tolerance in transgenic mice expressing self-tolerized B cells, and that 2) loss of tolerance in this model is associated with marked changes in surface expression of B cell coreceptors as well as with selective changes in IgD-induced signaling by discrete tyrosine-phosphoproteins, but not Syk kinase.

Animals↗

The multicomponent automated dissolution system: an alternative in the development and pharmaceutical analysis of generic polydrugs.

The necessity of assuring the quality of polydrugs, especially those with low aqueous solubility and in vivo absorption, has led to the development and evaluation of new techniques that can reduce the time and cost of analysis. This study examines the efficiency and accuracy of an automated dissolution system, fitted with an integrated multicomponent detector, for analysis of generic polydrugs using multiple linear regression (MLR). Trimethoprim and sulphamethoxazole were chosen as model drugs for this study and comparison was made with a conventional analysis based on HPLC. Both analytical systems under study gave reproducible and accurate results. Analysis of variance showed that there was no significant statistical difference between the methods of analysis, nor any statistical difference between the measured amounts of drug in the three different formulations. We have demonstrated that low cost instrumentation coupled with MLR data processing provides entirely satisfactory drug analysis to standard at least as good as that achieved using HPLC and provides an opportunity to reduce the time and analysis cost of other generic formulations.

Automation↗

Percutaneous mitral valvotomy in patients eighteen years old and younger. Immediate and late results.

OBJECTIVE - To analyze immediate and late results of percutaneous mitral valvotomy (PMV) in patients < or = 18 year. METHODS - Between August '87 and July '97, 48 procedures were performed on 40 patients. The mean age was 15.6 years; 68.7% were females four of whom were pregnant. RESULTS - Success was obtained in 91.7% of the procedures. Immediate complications were severe mitral regurgitation (6.3%) and cardiac tamponade (2.0%). Late follow-up was obtained in 88.8% of the patients (mean value=43.2+/-33.9 months). NYHA functional class (FC) I or II was observed in 96.2% of the patients and restenosis developed in five patients, at a mean follow-up of 29.7+/-11.9 months. Three patients presented with severe mitral insufficiency and underwent surgery. Two patients died. CONCLUSION - PMV represents a valid therapeutic option in young patients. In these patients, maybe because of subclinical rheumatic activity, restenosis may have a higher incidence and occur at an earlier stage than in others persons.

Adolescent↗

Medicare's new army.

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Centers for Medicare and Medicaid Services, U.S.↗

Escape from a PPMC.

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Contract Services↗

Closing the loophole.

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Employee Retirement Income Security Act↗