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Biomedical subjects

R Dias

Publications and source records attributed to R Dias.

At least 19 recordsLinked to original sources
PubMed2006

Antimicrobial susceptibility, serotype and genotype distribution of meningococci in Portugal, 2001-2002.

One hundred and eighteen Neisseria meningitidis isolates were recovered from patients with invasive meningococcal disease in Portugal, over one year. Our study was undertaken to evaluate antimicrobial susceptibility, serogroup, serotype and genotype of isolates. One quarter (24.6%) of the isolates showed moderate resistance to penicillin and 47.4% were resistant to sulphadiazine. The two most common serosubtypes were C:2b:P1.5,2 (31.3%) and B:4:P1.15 (3.4%). Half (53.6%) of the isolates with moderate resistance to penicillin were phenotype C:2b:P1.5,2 (n=14), C:2b:P1.2 (n=1) or C:2b:NST (n=1); Pulsed-field gel electrophoresis (PFGE) showed that all these isolates were genetically related. Multilocus sequence typing (MLST) analysis of representative clones from each PFGE pattern showed the predominance of the ST-8 complex/cluster A4 among N. meningitidis with moderate resistance to penicillin. This clonal complex has been principally found in Southern Europe. The apparent emergence and dissemination of the hypervirulent ST-8 complex/cluster A4 among serogroup C strains increases the need for a continued surveillance of antimicrobial susceptibility of meningococci and of genotypic markers in Portugal.

Anti-Infective Agents↗
PubMed2006

The discriminatory value of the low-dose dexamethasone suppression test in the investigation of paediatric Cushing's syndrome.

BACKGROUND: Low- and high-dose dexamethasone suppression tests (LDDST, HDDST) are used in the investigation of Cushing's syndrome (CS). In adults with Cushing's disease (CD), cortisol suppression during LDDST predicts suppression during the HDDST. METHODS: We reviewed the results of the LDDST (0.5 mg 6 hourly x 48 h), HDDST (2.0 mg 6 hourly x 48 h) and corticotrophin-releasing hormone (CRH) test in 32 paediatric patients with CS: 24 had CD, 1 ectopic ACTH syndrome, 5 nodular adrenal hyperplasia and 2 adrenocortical tumours. RESULTS: In CD, LDDST suppressed cortisol from 590.7 +/- 168.8 (mean +/- SD) to 333.7 +/- 104.0 nmol/l after 48 h (0 vs. 48 h, p < 0.05; mean suppression, 45.1%; CI (30.8, 59.4%); 16/24 (66%) suppressed >30%; mean suppression 68.1%, CI (58.1, 77.9%)). The HDDST suppressed cortisol from 596.3 +/- 174.5 to 47.1 +/- 94.8 nmol/l after 48 h (0 vs. 48 h, p < 0.05; mean suppression, 93.5%; CI (88.2, 98.8%) with 17/24 (71%) suppressing to <50 nmol/l and 100% to <50% of baseline). In the LDDST, suppression correlated with that during the HDDST (r = +0.45, p < 0.05) with >30% suppression predicting that in the HDDST and hence CD. CRH increased cortisol by +100.3% (CI 62, 138.5%), 22/24 (91.7%) showing a >20% increase. In the other CS pathologies (n = 8) the LDDST induced no significant decrease in cortisol. CONCLUSION: The LDDST was of diagnostic value by discriminating between CD and other CS aetiologies. In our view the HDDST is redundant in the investigation of paediatric CS.

Adolescent↗
PubMed2005

Surface complexation of DNA with insoluble monolayers. Influence of divalent counterions.

DNA interacts with insoluble monolayers made of cationic amphiphiles as well as with monolayers of zwitterionic lipids in the presence of divalent ions. Binding to dioctadecyldimethylammonium bromide (DODAB) or distearoyl-sn-glycero-3-phosphocholine (DSPC) monolayers in the presence of calcium is accompanied by monolayer expansion. For the positively charged DODAB monolayer, this causes a decrease of surface potential, while an increase is observed for the DSPC monolayers. Binding to dipalmitoyl-sn-glycero-3-phosphocholine preserves most of the liquid expanded-liquid condensed coexistence region. The liquid condensed domains adopt an elongated morphology in the presence of DNA, especially in the presence of calcium. The interaction of DNA with phospholipid monolayers is ion specific: the presence of calcium leads to a stronger interaction than magnesium and barium. These results were confirmed by bulk complexation studies.

Animals↗
PubMed2002

Involvement of the rat medial prefrontal cortex in novelty detection.

The prefrontal cortex in humans has been implicated in processes that underlie novelty detection and attention. This study examined the contribution of the rat medial prefrontal cortex to novelty detection using the targeting, or orienting, response (OR) as a behavioral index. Lesions to the medial prefrontal cortex (specifically the prelimbic and infralimbic cortices) influenced neither the OR to a novel visual stimulus from a localized light source (V1), nor the change in this OR over the course of a series of exposures to V1. However, after exposure to V1, the OR to a 2nd visual stimulus from the same source, V2, was more pronounced in control rats than in lesioned rats. These results suggest that the medial prefrontal cortex in the rat contributes to the process of novelty detection.

Animals↗
PubMed2002

DNA-lipid systems. A physical chemistry study.

It is well known that the interaction of polyelectrolytes with oppositely charged surfactants leads to an associative phase separation; however, the phase behavior of DNA and oppositely charged surfactants is more strongly associative than observed in other systems. A precipitate is formed with very low amounts of surfactant and DNA. DNA compaction is a general phenomenon in the presence of multivalent ions and positively charged surfaces; because of the high charge density there are strong attractive ion correlation effects. Techniques like phase diagram determinations, fluorescence microscopy, and ellipsometry were used to study these systems. The interaction between DNA and catanionic mixtures (i.e., mixtures of cationic and anionic surfactants) was also investigated. We observed that DNA compacts and adsorbs onto the surface of positively charged vesicles, and that the addition of an anionic surfactant can release DNA back into solution from a compact globular complex between DNA and the cationic surfactant. Finally, DNA interactions with polycations, chitosans with different chain lengths, were studied by fluorescence microscopy, in vivo transfection assays and cryogenic transmission electron microscopy. The general conclusion is that a chitosan effective in promoting compaction is also efficient in transfection.

Cations↗
PubMed2001

Perirhinal cortex and place-object conditional learning in the rat.

The present study examined whether excitotoxic lesions of the perirhinal cortex can affect acquisition of a place-object conditional task in which object and spatial information must be integrated. Testing was carried out in a double Y-maze apparatus, in which rats learned a conditional rule of the type, "In Place X, choose Object A, not Object B (A+ vs. B-); in Place Y, choose Object B, not Object A (A- vs. B+)." Perirhinal cortex lesions significantly impaired acquisition of this task while sparing performance of an allocentric spatial memory task performed in a radial arm maze. Perirhinal cortex lesions also had no apparent effect on a 1-pair object discrimination task performed in the double Y maze or on retention and acquisition of 4-pair concurrent discrimination problems performed in a computer-automated touch screen testing apparatus. The results suggest that, although the perirhinal cortex and hippocampus can be functionally dissociated, their normal mode of operation includes the integration of object and spatial information.

Animals↗
PubMed2001

Dissociable contributions of the orbitofrontal and lateral prefrontal cortex of the marmoset to performance on a detour reaching task.

To gain insight into the nature and neural specificity of the relationship between simple problem solving, inhibitory control and prefrontal cortex, comparison of the effects of excitotoxic lesions of the orbitofrontal and lateral prefrontal cortex were examined on the performance of common marmosets on a detour reaching task. Monkeys were required to inhibit reaching directly for food reward in a transparent box and instead make a detour reach around to the side of the box either having had (i) no prior experience on the task (experiment 1) or (ii) previous experience in reaching around the sides of an opaque box (experiment 2). Whilst monkeys with orbitofrontal lesions had difficulty in inhibiting direct reaches to visible food reward (experiment 1), they could resist this prepotent response tendency following extensive prior experience of detour reaching with an opaque box (experiment 2). In marked contrast, monkeys with lateral prefrontal lesions exhibited no difficulty in inhibiting reaching to visible food reward or acquiring detour reaching per se (experiment 1). However, having been given the opportunity to acquire an efficient detour reaching strategy to hidden food reward these lateral prefrontal lesioned monkeys were impaired at transferring this strategy to the new context in which the food reward was made visible (experiment 2). This double dissociation between the effects of orbitofrontal and lateral prefrontal lesions on detour reaching provides evidence for a clear distinction in the level of control over responding exerted by the orbitofrontal and lateral prefrontal cortex, consistent with hierarchical ordering of response control processes within prefrontal cortex.

Animals↗
PubMed2001

Pharmacologic insights into the future of trastuzumab.

A combination of factors has been responsible for improvements in cancer survival and cure rates. In addition to new therapies with novel/genetic targets, these include improvements in drug delivery, new schedules/sequencing of drug administration and the identification of combination therapies with greater activity/dose density than existing regimens. The recognition that such criteria can affect treatment outcome has led to their incorporation into clinical trials of new drugs. Furthermore, pharmacokinetic and pharmacodynamic parameters have become increasingly important for the rational selection of dose, administration route and schedule. The humanized monoclonal antibody trastuzumab (Herceptin) has been rationally developed to target the human epidermal growth factor receptor-2 (HER2), which is overexpressed in 20%-30% of breast cancers and is associated with poor prognosis. Trastuzumab when administered i.v. on a weekly schedule either alone or in combination with taxanes, improves survival of women with HER2-positive metastatic breast cancer. Based upon pharmacokinetic considerations, current studies are examining whether trastuzumab can be administered i.v. every three weeks or by the s.c. route. These regimens would have advantages for patients and medical staff in terms of acceptability, ease of administration and, potentially, cost effectiveness. Furthermore, various combinations of trastuzumab and chemotherapeutic agents are being explored with the aim of identifying the optimal combination regimen for clinical use. The rationale for these various studies and the studies themselves are described.

Antibodies, Monoclonal↗
PubMed2001

Positive effect of etidronate therapy is maintained after drug is terminated in patients using corticosteroids.

Following a 52-wk randomized controlled trial of intermittent cyclic etidronate therapy in patients using corticosteroids, we performed a 52-wk open-label trial of calcium alone in 114 corticosteroid-treated patients to determine whether the beneficial effect of etidronate is maintained after the drug is discontinued. All patients were given 500 mg/d of elemental calcium. Sixty-one and 53 patients made up the former placebo and etidronate groups, respectively. A total of 89 (98%) of patients in the former placebo and etidronate groups remained on corticosteroids throughout the second year. The mean (SE) percentage change in bone mineral density of the lumbar spine, femoral neck, and trochanter were compared between groups. The difference between groups in mean percentage change from baseline (wk 0, initiation of etidronate or placebo therapy) in the bone density of the lumbar spine, femoral neck, and trochanter, following 104 wk, was 3.8 (0.9), 3.0 (1.1), and 4.3 (1.1), respectively (p < 0.05, all sites), in favor of the former etidronate group. While not significant, the former placebo group demonstrated a slightly larger rate of decline in bone density over the second year than the former etidronate group at all three sites. Following the discontinuation of etidronate therapy, there was no accelerated bone loss and there was evidence of a residual protective effect in both the lumbar spine and femoral neck for up to 1 yr posttreatment.

Adult↗
PubMed2000

Intact negative patterning in rats with fornix or combined perirhinal and postrhinal cortex lesions.

It has been proposed that the hippocampal formation is necessary for the acquisition of tasks that require the use of configural representations for their solution, including spatial learning and negative patterning. Tests of this influential view have, however, yielded conflicting results. For example fornix or hippocampal lesions, which reliably impair spatial learning, do not reliably impair negative patterning. A problem in interpreting these results has been the lack of controls for factors such as over-responding, excitatory effects of reward, and the possibility of non-configural solutions. At the same time, other studies have pointed to a role in configural learning for parahippocampal regions such as the perirhinal cortex. The present experiments controlled for the above factors and revealed that neither lesions of the fornix nor of the perirhinal/postrhinal cortex in the rat had any effect on negative patterning, although subsequent tests of object and spatial memory demonstrated the functional efficacy of the lesions.

Amygdala↗
PubMed2000

Effects of selective excitotoxic prefrontal lesions on acquisition of nonmatching- and matching-to-place in the T-maze in the rat: differential involvement of the prelimbic-infralimbic and anterior cingulate cortices in providing behavioural flexibility.

The present study investigated the contributions of the medial prefrontal cortex and its major subdivisions, the dorsal anterior cingulate (ACd) and prelimbic-infralimbic (PL) cortices, to spatial working memory and inhibitory control processes. In experiment 1, excitotoxic lesions centred in the ACd or PL cortex did not affect acquisition of a nonmatching-to-place task in the T-maze with a retention interval of 10 s. However, the same reinforced alternation task was impaired by larger prefrontal lesions that combined ACd and PL cortices. In experiment 2, new animals were trained on a matching-to-place task in the T-maze that uses a rule counter to the animals' innate bias to alternate spontaneously. Now, discrete lesions of both the ACd and PL cortices impaired acquisition, but in different ways. Both animals with PL and with ACd lesions perseverated by nonmatching for more sessions than the controls, but only the PL animals also showed a more general increase in perseveration reflected in a further, extended period of applying an inefficient response rule (e.g. always turn right) and a deficit at reversing from matching to nonmatching. Acquisition of the matching-to-place task was also impaired by combined lesions of ACd and PL cortices. Overall, whilst spatial working memory processes appear to remain intact in those animals with discrete prefrontal lesions, the present findings provide strong evidence for the differential involvement of the prelimbic-infralimbic and anterior cingulate regions in providing behavioural flexibility.

Animals↗
PubMed2000

Serological detection of Gram-positive bacterial infection around prostheses.

Coagulase-negative staphylococci produce an exocellular glycolipid antigen which has potential as a serological marker of infection in bone. The value of this newly detected antigen was investigated by enzyme-linked immunosorbent assay (ELISA) in 15 patients with culture-proven infection of prostheses caused by Gram-positive bacteria. The antigen was purified by gel-permeation chromatography from the culture supernatants of coagulase-negative staphylococci grown in a chemically defined medium. There were significant differences (p < 0.0001) between the serum IgG and IgM levels in patients with infection due to Gram-positive staphylococci and those of a control group of 32 patients with no infection. The ELISA test, which has potential for the diagnosis of infection, may be valuable in distinguishing between staphylococcal infection around prostheses and aseptic loosening.

Adult↗
PubMed1999

DNA conformational dynamics in the presence of catanionic mixtures.

DNA conformational behavior in the presence of non-stoichiometric mixtures of two oppositely charged surfactants, cetyltrimethylammonium bromide and sodium octyl sulfate, was directly visualized in an aqueous solution with the use of a fluorescence microscopy technique. It was found that in the presence of cationic-rich catanionic mixtures, DNA molecules exhibit a conformational transition from elongated coil to compact globule states. Moreover, if the catanionic mixtures form positively charged vesicles, DNA is adsorbed onto the surface of the vesicles in a collapsed globular form. When anionic-rich catanionic mixtures are present in the solution, no change in the DNA conformational behavior was detected. Cryogenic transmission electron microscopy, as well as measurements of translational diffusion coefficients of individual DNA chains, supported our optical microscopy observations.

Anions↗
PubMed1998

Perseveration and strategy in a novel spatial self-ordered sequencing task for nonhuman primates: effects of excitotoxic lesions and dopamine depletions of the prefrontal cortex.

Damage to the prefrontal cortex disrupts the performance of self-ordered sequencing tasks, although the precise mechanisms by which this effect occurs is unclear. Active working memory, inhibitory control, and the ability to generate and perform a sequence of responses are all putative cognitive abilities that may be responsible for the impaired performance that results from disruption of prefrontal processing. In addition, the neurochemical substrates underlying prefrontal cognitive function are not well understood, although active working memory appears to depend upon an intact mesocortical dopamine system. The present experiments were therefore designed to evaluate explicitly the contribution of each of these abilities to successful performance of a novel spatial self-ordered sequencing task and to examine the contribution of the prefrontal cortex and its dopamine innervation to each ability in turn. Excitotoxic lesions of the prefrontal cortex of the common marmoset profoundly impaired the performance of the self-ordered sequencing task and induced robust perseverative responding. Task manipulations that precluded perseveration ameliorated the effect of this lesion and revealed that the ability to generate and perform sequences of responses was unaffected by excitotoxic damage to prefrontal cortex. In contrast, large dopamine and noradrenaline depletions within the same areas of prefrontal cortex had no effect on any aspect of the self-ordered task but did impair the acquisition of an active working memory task, spatial delayed response, to the same degree as the excitotoxic lesion. These results demonstrate that a lesion of the ascending monoamine projections to the prefrontal cortex is not always synonymous with a lesion of the prefrontal cortex itself and thereby challenge existing concepts concerning the neuromodulation of prefrontal cognitive function.

Animals↗
PubMed1997

Dissociable forms of inhibitory control within prefrontal cortex with an analog of the Wisconsin Card Sort Test: restriction to novel situations and independence from "on-line" processing.

Attentional set-shifting and discrimination reversal are sensitive to prefrontal damage in the marmoset in a manner qualitatively similar to that seen in man and Old World monkeys, respectively (Dias et al., 1996b). Preliminary findings have demonstrated that although lateral but not orbital prefrontal cortex is the critical locus in shifting an attentional set between perceptual dimensions, orbital but not lateral prefrontal cortex is the critical locus in reversing a stimulus-reward association within a particular perceptual dimension (Dias et al., 1996a). The present study presents this analysis in full and extends the results in three main ways by demonstrating that (1) mechanisms of inhibitory control and "on-line" processing are independent within the prefrontal cortex, (2) impairments in inhibitory control induced by prefrontal damage are restricted to novel situations, and (3) those prefrontal areas involved in the suppression of previously established response sets are not involved in the acquisition of such response sets. These findings suggest that inhibitory control is a general process that operates across functionally distinct regions within the prefrontal cortex. Although damage to lateral prefrontal cortex causes a loss of inhibitory control in attentional selection, damage to orbitofrontal cortex causes a loss of inhibitory control in affective processing. These findings provide an explanation for the apparent discrepancy between human and nonhuman primate studies in which disinhibition as measured on the Wisconsin Card Sort Test is associated with dorsolateral prefrontal damage, whereas disinhibition as measured on discrimination reversal is associated with orbitofrontal damage.

Animals↗