Biomedical subjects

M Fernandez

Publications and source records attributed to M Fernandez.

At least 55 records · Page 3Linked to original sources

PubMed2001

Context dependent latent inhibition in adult humans.

Learning the association between one stimulus (a condition stimulus, CS) and another (unconditioned stimulus, US) can be impaired by prior exposure to the CS alone--latent inhibition (LI). Current theories attempting to elucidate the cognitive deficit in schizophrenia have used the abolition of LI in schizophrenia as an indicator of attentional dysfunction. However, it has always been unclear if human and animal LI are measuring the same psychological processes. It is obviously important to clarify this relationship so that theoretical and experimental developments in the rat do not mislead the investigation of brain-behaviour relationships in schizophrenia. LI in the rat is strongly dependent upon context. Our aim was to examine the context specificity of LI in humans and specifically to: (1) investigate whether participants' belief that they are in a different context is sufficient to abolish LI, even though there is no physical change in the environment; (2) produce a context manipulation that is immune to alternative interpretation in terms of stimulus generalization decrement; and (3) investigate whether a "tonic" change of context reduces or abolishes human LI, thus complementing previous reports using a "phasic" change of context. In two experiments we manipulated context in either the real world or a virtual world, and showed that LI is abolished by a change of context in adult humans.

Adolescent↗

PubMed2001

Impact of a multimedia breast cancer education intervention on use of mammography by low-income Latinas.

BACKGROUND: This paper describes the results of a study of a multimedia breast cancer educational intervention for low-education, low-income Latinas. METHODS: Study participants were first exposed to an interactive, multimedia breast cancer educational intervention and then interviewed four months later to ascertain their mammography status. RESULTS: About 40% of the women who had either obtained or scheduled mammography since the intervention attributed their decision to the intervention. CONCLUSION: Women who had previously been screened and who understood that mammography was used as a breast cancer screening method were more likely to have scheduled or obtained mammography than other women.

Adult↗

PubMed2001

Microphthalmia transcription factor in the immunohistochemical diagnosis of metastatic melanoma: comparison with four other melanoma markers.

The diagnosis of metastatic malignant melanoma (MMM) may be difficult in surgical pathology, often complicated by the unpredictable spread of this tumor and its great variability on histologic evaluation. Traditionally used immunohistochemical markers on melanomas are insufficient because of either a relative lack of specificity (S100 protein) or variably reported sensitivity (HMB45). Information about some newer markers, such as tyrosinase (TYR) and Melan A, is more limited. Recently, based on the study of a small number of tumors, it was suggested that microphthalmia transcription factor (MITF) is 100% sensitive in the identification of metastatic melanoma. In the current study, we compared the diagnostic usefulness of MITF with that of four other markers in 266 cases of conventional metastatic melanomas from different sites, 33 cases of desmoplastic melanomas, and 1 case of melanoma with rhabdoid features. The specificity of MITF was evaluated by using a representative sample of control tumors. Microphthalmia transcription factor with nuclear positivity was seen in 235 of 266 cases of conventional MMM (88%), usually in more than 30% of tumor cells. However, some melanomas had only foci of MITF- and TYR-positive cells, whereas the majority of cells were generally S100 protein-positive. Only 1 of 30 desmoplastic melanomas (3%) had MITF-positive cells, representing epithelioid foci resembling conventional melanoma. Two cases had TYR in a similar pattern; all were HMB45-negative. One metastatic melanoma with rhabdoid features was negative for MITF and other markers except the S100 protein. Half of the S100 protein negative conventional melanomas (6 of 12) were MITF-positive, whereas 4 of 20 (20%) TYR-negative tumors had reactivity for MITF. The percentages of positive cases of MMM (10% or more tumor cells positive) diagnosed with the four other markers in descending order were 90% (S100 protein and TYR), 78% (melan-A), and 66% (HMB45). Microphthalmia transcription factor appeared to be specific, because significant reactivity was not found in 112 carcinomas, 20 lymphomas, 20 angiosarcomas, 20 fibrous histiocytomas, and 20 malignant peripheral nerve sheath tumors. However, positive nuclei were found focally among reactive histiocytes, especially in osteoclasts, epithelioid histiocytes, and sporadic other histiocytes. Microphthalmia transcription factor may be a valuable addition to the marker panel used in diagnosing melanoma, in combination with S100, TYR, and the other markers, but it is not present in cases of desmoplastic melanomas.

Angiomyolipoma↗

PubMed2001

Failure of rifampin to eradicate group B streptococcal colonization in infants.

BACKGROUND: Mucous membrane colonization with group B streptococci (GBS) frequently persists in infants after treatment of invasive infection and may be associated with recurrent disease. OBJECTIVE: To determine the frequency with which GBS colonization persists at mucous membrane sites after treatment of invasive early or late onset infection and to determine the efficacy of oral rifampin in eradicating colonization in these infants and their mothers. METHODS: Cultures for isolation of GBS were obtained from infants and their mothers after completion of the infant's parenteral therapy, 1 week later when rifampin therapy was initiated and at approximately 1 and 4 weeks after completion of rifampin therapy. Rifampin was administered (10-mg/kg dose; maximum, 600 mg) twice daily for 4 days. RESULTS: Ten of 21 infants (48%) and 13 (65%) of their 20 mothers were colonized with GBS at throat or rectal (infant) or vaginal, rectal or breast milk (mother) sites before rifampin was initiated. One week or less after rifampin treatment, 7 (70%) infants and 4 (31%) mothers remained colonized with GBS. At study completion 6 infants and 7 mothers had GBS colonization. Persistent colonization was not related to GBS serotype, to initial rifampin minimal inhibitory concentration or to the development of rifampin resistant strains. CONCLUSIONS: Rifampin treatment for four days utilized as a single agent after completion of parenteral therapy failed to reliably eradicate GBS colonization in infants.

Anti-Bacterial Agents↗

PubMed2001

Familial dyskinesia and facial myokymia (FDFM): a novel movement disorder.

We describe here familial dyskinesia and facial myokymia (FDFM), a novel autosomal dominant disorder characterized by adventitious movements that sometimes appear choreiform and that are associated with perioral and periorbital myokymia. We report a 5-generation family with 18 affected members (10 males and 8 females) with FDFM. The disorder has an early childhood or adolescent onset. The involuntary movements are paroxysmal at early ages, increase in frequency and severity, and may become constant in the third decade. Thereafter, there is no further deterioration, and there may even be improvement in old age. The adventitious movements are worsened by anxiety but not by voluntary movement, startle, caffeine, or alcohol. The disease is socially disabling, but there is no intellectual impairment or decrease in lifespan. A candidate gene and haplotype analysis was performed in 9 affected and 3 unaffected members from 3 generations of this family using primers for polymorphic loci closely flanking or within genes of interest. We excluded linkage to 11 regions containing genes associated with chorea and myokymia: 1) the Huntington disease gene on chromosome 4p; 2) the paroxysmal dystonic choreoathetosis gene at 2q34; 3) the dentatorubral-pallidoluysian atrophy gene at 12p13; 4) the choreoathetosis/spasticity disease locus on 1p that lies in a region containing a cluster of potassium (K+) channel genes; 5) the episodic ataxia type 1 (EA1) locus on 12p that contains the KCNA1 gene and two other voltage-gated K+ channel genes, KCNA5 and KCNA6; 6) the chorea-acanthocytosis locus on 9q21; 7) the Huntington-like syndrome on 20p; 8) the paroxysmal kinesigenic dyskinesia locus on 16p11.2-q11.2; 9) the benign hereditary chorea locus on 14q; 10) the SCA type 5 locus on chromosome 11; and 11) the chromosome 19 region that contains several ion channels and the CACNA1A gene, a brain-specific P/Q-type calcium channel gene associated with ataxia and hemiplegic migraine. Our results provide further evidence of genetic heterogeneity in autosomal dominant movement disorders and suggest that a novel gene underlies this new condition.

Adolescent↗

PubMed2000

Differential effects of acute and short-term lithium administration on dialysate glutamate and GABA levels in the frontal cortex of the conscious rat.

In the present study, we employed in vivo microdialysis in the frontal cortex of the awake rat to investigate the effects of acute and short-term (twice daily, 3 days) lithium chloride administration (1, 2, and 4 meq/kg, s.c.) on local dialysate glutamate and GABA levels. Acute lithium (1 meq/kg) failed to influence cortical glutamate levels while the higher (2 and 4 meq/kg) doses increased (+38 +/- 6% of basal levels) and reduced (-27 +/- 4%) cortical glutamate levels, respectively. Cortical GABA levels were affected by acute lithium only at the highest 4 meq/kg dose (+62 +/- 6%). Furthermore, these effects were prevented by tetrodotoxin (1 microM) and low-calcium (0.2 mM) medium perfusion. Following short-term administration, lithium increased (+58 +/- 4%) cortical dialysate glutamate levels at the 1 meq/kg dose, was ineffective at 2 meq/kg, while the effect of the 4 meq/kg dose was similar to that observed after acute administration. Interestingly, intracortical perfusion with the GABA(B) receptor antagonist CGP 35348 (100 microM) reversed the acute lithium (4 meq/kg)-induced decrease in glutamate levels. Taken together, these findings indicate a differential dose and duration dependent effect of lithium on cortical dialysate glutamate levels involving both a direct enhancement and an indirect inhibition that is mediated via an activation of local GABA(B) receptor. These findings may be relevant for the therapeutic effects of the drug.

Animals↗

PubMed2000

Angiotensin I-converting enzyme transition state stabilization by HIS1089: evidence for a catalytic mechanism distinct from other gluzincin metalloproteinases.

Angiotensin (Ang) I-converting enzyme (ACE) is a member of the gluzincin family of zinc metalloproteinases that contains two homologous catalytic domains. Both the N- and C-terminal domains are peptidyl-dipeptidases that catalyze Ang II formation and bradykinin degradation. Multiple sequence alignment was used to predict His(1089) as the catalytic residue in human ACE C-domain that, by analogy with the prototypical gluzincin, thermolysin, stabilizes the scissile carbonyl bond through a hydrogen bond during transition state binding. Site-directed mutagenesis was used to change His(1089) to Ala or Leu. At pH 7.5, with Ang I as substrate, k(cat)/K(m) values for these Ala and Leu mutants were 430 and 4,000-fold lower, respectively, compared with wild-type enzyme and were mainly due to a decrease in catalytic rate (k(cat)) with minor effects on ground state substrate binding (K(m)). A 120,000-fold decrease in the binding of lisinopril, a proposed transition state mimic, was also observed with the His(1089) --> Ala mutation. ACE C-domain-dependent cleavage of AcAFAA showed a pH optimum of 8.2. H1089A has a pH optimum of 5.5 with no pH dependence of its catalytic activity in the range 6.5-10.5, indicating that the His(1089) side chain allows ACE to function as an alkaline peptidyl-dipeptidase. Since transition state mutants of other gluzincins show pH optima shifts toward the alkaline, this effect of His(1089) on the ACE pH optimum and its ability to influence transition state binding of the sulfhydryl inhibitor captopril indicate that the catalytic mechanism of ACE is distinct from that of other gluzincins.

Amino Acid Sequence↗

PubMed2000

Candidal meningitis in neonates: a 10-year review.

Candidal meningitis may complicate systemic candidiasis in the premature neonate. We conducted a 10-year retrospective review of 106 cases of systemic candidiasis in neonates to define the incidence, clinical features, laboratory findings, treatment, and outcome of candidal meningitis. Twenty-three of the 106 neonates had candidal meningitis (0.4% of admissions to the neonatal intensive care unit). The median gestational age was 26.2 weeks, the median birth weight was 820 g, and the median age at the onset of illness was 8 days. Clinical disease was severe and commonly was manifested by respiratory decompensation. Findings of cerebrospinal fluid (CSF) analyses varied: pleocytosis was inconsistent, hypoglycorrhachia was common, gram staining was uniformly negative, and Candida was isolated from 17 neonates (74%). Each infant was treated with amphotericin B (median cumulative dose, 30 mg/kg); 5 also received flucytosine therapy. In conclusion, initial clinical features of candidal meningitis are indistinguishable from those of other causes of systemic infection in premature neonates, and normal CSF parameters do not exclude meningitis. Timely initiation of amphotericin B monotherapy was associated with an excellent outcome.

Antifungal Agents↗

PubMed2000

Amplification of cortical serotonin release: a further neurochemical action of the vigilance-promoting drug modafinil.

The present in vitro and in vivo studies examined the effects of modafinil on serotonergic transmission in the rat frontal cortex. In the in vitro study modafinil (0.3-30 microM) increased electrically-evoked, but not spontaneous, serotonin ([(3)H]5-HT) efflux from cortical slices in a concentration-dependent manner while the indirect serotonin agonist dl-fenfluramine (1-15 microM) enhanced both spontaneous and evoked [(3)H]5-HT efflux. The effects of modafinil were more pronounced when the 5-HT reuptake was blocked by paroxetine. Contrary to paroxetine (0.3-3 microM) and dl-fenfluramine (1-5 microM), modafinil failed to influence the [(3)H]5-HT uptake. In the in vivo study modafinil (3-100 mg/kg i.p.) increased 5-HT dialysate levels, the maximal effect being already reached at the 30 mg/kg dose. dl-fenfluramine (5 mg/kg) induced an increase in 5-HT levels which was significantly higher than that displayed by modafinil at 30 mg/kg. In the presence of paroxetine (3 microM), the effect of modafinil at 30 mg/kg was higher than that observed in the absence of 5-HT reuptake inhibition. Finally, in the presence of the selective 5-HT(1A) receptor agonist 8-OH-DPAT, modafinil at 100 mg/kg failed to affect 5-HT dialysate levels. These results demonstrate that modafinil regulates cortical serotonergic transmission and suggest that the drug preferentially acts by amplifying the electro-neurosecretory coupling mechanisms and via mechanisms which do not involve the reuptake process.

Animals↗

PubMed2000

Late-onset SCA2: 33 CAG repeats are sufficient to cause disease.

SCA-2 is an autosomal dominant inherited disorder characterized by ataxia, slow saccades, and hyporeflexia. The authors evaluated a patient with a mild balance problem with a SCA-2 allele sized at 33 CAG repeats. The authors then ascertained her 91 year-old mother, who showed disease onset at age 86 with an SCA-2 allele of identical size. Their study indicates that 33 CAG repeats can be pathogenic at the SCA-2 locus, though such an allele may produce an extremely late onset and gradual rate of disease progression.

Aged↗

PubMed2000

Restoration of facial contour in Romberg's disease and hemifacial microsomia: experience with 118 cases.

The experience with free flaps and conventional reconstructive procedures for 118 patients with Rombergapos;s disease and hemifacial microsomia over a 10-year period is presented. The groin free flap was used most frequently for patients with Rombergapos;s disease, whereas the scapular free flap was used for patients with hemifacial microsomia. The rectus abdominis or the latissimus dorsi free flap was chosen only when additional volume was required. To achieve better contour, secondary procedures, such as defatting the flap, pedicled temporal fascial flaps, cartilage and bone grafts, orthognathic surgery, and bone distraction were performed in severe cases. For patients with Rombergapos;s disease, excellent results were achieved in 35% (n = 28) of mild cases, in 72% (n = 27) out of 38 moderately and in 41% (n = 5) out of 12 severely affected patients. In hemifacial microsomia group (n = 40) excellent results were obtained in 66% of cases.

Adult↗

PubMed2000

Glucocorticoids drive human CD8(+) T cell differentiation towards a phenotype with high IL-10 and reduced IL-4, IL-5 and IL-13 production.

Glucocorticoids are highly effective in the treatment of allergy and asthma and inhibit the synthesis of IL-4, IL-5 and IL-13 by disease-promoting CD4(+) Th2 cells. CD8(+) T cells also synthesize these cytokines, and the aim of this study was to investigate how glucocorticoids effect cytokine production by these cells. When CD8(+) T cells are stimulated with anti-CD3 and IL-2 plus IL-4 or dexamethasone, production of the anti-inflammatory cytokine IL-10 is low in both primary and secondary cultures restimulated with anti-CD3 and IL-2 alone. However, when both are present, a synergistic effect on IL-10 synthesis is observed. The additional presence of antigen-presenting cells (APC) in the priming culture maintains IL-10 levels, but inhibits IL-4 and IL-5 production. CD4(+) T cells develop a similar glucocorticoid-induced phenotype. These cells demonstrate regulatory activity and inhibit CD4(+) T cell activation in an IL-10-dependent manner. Earlier reports show glucocorticoids promote a Th2 phenotype by effects on purified naive T cells or pretreatment of APC. This study demonstrates, more critically, that when APC are present, glucocorticoids induce CD4 and CD8 T cell populations synthesizing high levels of IL-10, but greatly reduced amounts of disease-promoting IL-4 and IL-5.

Adult↗

PubMed2000

Duration of the hemodynamic effects of N(G)-nitro-L-arginine methyl ester in vivo.

The objective of this study was to quantify the duration of the hemodynamic activity of N(G)-nitro-l-arginine methyl ester (l-NAME) in a variety of different tissues following a single bolus injection of this nitric oxide synthase inhibitor to healthy rats. l-NAME (15 micromol x kg(-1)) was injected (ip) into rats to produce maximal inhibition of endothelial cell NOS. Animals were subsequently anesthetized and blood flow was quantified using the radioactive microsphere/reference organ technique. At 1 h following a single bolus injection of l-NAME blood flow was reduced to the entire gastrointestinal tract, pancreas, and liver. Three hours following l-NAME administration, blood flow to the stomach and upper small intestine had returned to pretreatment levels; however, blood flow to the jejunum, ileal-jejunal junction, and colon remained significantly reduced. Splenic blood flow was significantly reduced and hepatic arterial blood flow was further reduced at this time as well. After 6 h following l-NAME administration, blood flow in all organs had completely recovered to control levels. Although cardiac index and total peripheral resistance had also returned to preinjection values at this time, mean arterial pressure remained elevated at 6 h posttreatment. Blood flow to the brain, lungs, and psoas muscle were unaffected by l-NAME administration at any time point. Taken together, these data demonstrate a differential regulation of vascular tone by NO in different vascular beds and, depending upon the organ system in question, the vasoactive activity of l-NAME may last from 3 to 6 h following a single bolus injection of this NOS inhibitor.

Animals↗

PubMed2000

Regulation of the futile cycle of fructose phosphate in sea mussel.

Carbohydrate metabolism in mussels shows two phases separated seasonally. During summer and linked to food supply, carbohydrates, mainly glycogen, are accumulated in the mantle tissue. During winter, mantle glycogen decreases concomitantly with an increase in triglyceride synthesis. In spring, after spawning, the animals go in to metabolic rest until the beginning of a new cycle. This cycle is regulated by the futile cycle of fructose phosphate that implicates PFK-1 and FBPase-1 activities. These enzymes and the bifunctional PFK-2/FBPase-2 that regulates the Fru-2,6-P2 levels, are seasonally modulated by covalent phosphorylation/dephosphorylation mechanisms, as a response to unknown factors. The futile cycle of the fructose phosphates also controls the transition from physiological aerobiosis to hypoxia. The process is independent of the phosphorylation state. In this sense, a pH decrease triggers a small Pasteur effect during the first 24 h of aerial exposure. Variations in the concentration of Fru-2,6-P2 and AMP are the sole factor responsible for this effect. Longer periods of hypoxia induce a metabolic depression characterized by a decrease in Fru-2,6-P2 which is hydrolyzed by drop in the pH. In this review, the authors speculate on the two regulation processes.

Animals↗

PubMed2000

Watch, Discover, Think, and Act: a model for patient education program development.

In this report we describe the development of the Watch, Discover, Think and Act asthma self-management computer program for inner-city children with asthma. The intervention focused on teaching two categories of behaviors--asthma specific behaviors such as taking preventive medication and self-regulatory processes such as monitoring symptoms and solving asthma problems. These asthma self-management behaviors were then linked with empirical and theoretical determinants such as skills and self-efficacy. We then further used behavioral science theory to develop methods such as role modeling and skill training linked to the determinants. We matched these theoretical methods to practical strategies within the computer simulation and created a culturally competent program for inner-city minority youth. Finally, we planned a program evaluation that linked program impact and outcomes to the theoretical assumptions on which the intervention was based.

Asthma↗

PubMed2000

Watch, Discover, Think, and Act: evaluation of computer-assisted instruction to improve asthma self-management in inner-city children.

An interactive multimedia computer game to enhance self-management skills and thereby improve asthma outcomes in inner city children with asthma was evaluated. Subjects aged 6-17 were recruited from four pediatric practices and randomly assigned to the computer intervention condition or to the usual-care comparison. The main character in the game could match the subject on gender and ethnicity. Characteristics of the protagonist's asthma were tailored to be like those of the subject. Subjects played the computer game as part of regular asthma visits. Time between pre- and post-test varied from 4 to 15.6 months (mean, 7.6 months). Analysis of covariance, with pre-test scores, age, and asthma severity as covariates, found that the intervention was associated with fewer hospitalizations, better symptom scores, increased functional status, greater knowledge of asthma management, and better child self-management behavior for those in the intervention condition. Interactions with covariates were found and discussed in terms of variable efficacy of the intervention.

Asthma↗

PubMed2000

Serological prevalence to six leptospiral serovars in cattle in Asturias (Northern Spain).

The prevalence of antibody to six serovars of Leptospira interrogans in cattle in Asturias (Northern Spain) was determined by the microscopic agglutination test (MAT). Using 50% agglutination or lysis at a dilution of 1:10 or more as the criteria for seropositivity, 371 of 3578 (10.36%) animals were found to react with one serovar. The most commonly detected serovars were pomona (5.59%) and grippotyphosa (2.37%), whilst serovar hardjo (0.75%), icterohaemorrhagiae (0.64%), poi (0.64%) and autumnalis (0.36%) were found at lower frequencies.

Agglutination Tests↗

PubMed2000

A 5-year review of recurrent group B streptococcal disease: lessons from twin infants.

Recurrent invasive disease due to group B Streptococcus (GBS) in twin infants has not been reported. We report 2 cases of recurrent GBS afflicting both siblings of a set of dichorionic twin infants. The maternal and infant colonizing and invasive strains were identical by serotyping and pulsed-field gel electrophoresis (PFGE). Despite attempts at eradication with different antibiotic regimens, the infants remained colonized after treatment of the second episode. A 5-year review of recurrent invasive GBS disease in infants in our affiliated hospitals was undertaken, and 6 further cases were identified. Serotyping and PFGE of isolates from initial and second episodes were genotypically identical for each case. Three infants each had GBS serotype Ia or V disease and 2 had GBS serotype III disease. The exact pathogenesis of recurrent GBS disease remains unclear, but our data support the hypothesis that persistent mucosal colonization with the original GBS strain rather than new acquisition is a pivotal factor in disease recurrence.

Bacteremia↗