Central serous chorioretinopathy in a patient using methylenedioxymethamphetamine (MDMA) or "ecstasy".
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Biomedical subjects
Publications and source records attributed to C Carvalho.
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OBJECTIVE: To better define the effect of individual risk factors and combinations thereof on the growth of small choroidal melanocytic tumors. DESIGN: Retrospective analysis. SETTING: Clinical practice of ocular oncology. PATIENTS: The study included 1287 patients with small suspicious choroidal melanocytic tumors, measuring 3 mm or less in thickness, managed with observation. RESULTS: On multivariate analysis, the clinical risk factors predictive of growth of small choroidal melanocytic tumors include tumor thickness greater than 2.0 mm, posterior tumor margin touching the disc, visual symptoms, orange pigment, and subretinal fluid. Tumor growth was detected in 4% of those patients with no risk factors. Growth was detected in approximately 36% of patients with 1 risk factor, 45% of patients with 2 risk factors, 50% of patients with 3 risk factors, 51% of patients with 4 risk factors, and 56% of patients with all 5 risk factors. The combination of risk factors offering the greatest risk for growth was tumor thickness greater than 2.0 mm, tumor margin touching disc, and subretinal fluid that was associated with tumor growth in 63% of the affected patients. The relative risk for growth was 1.9 for 1 factor, 3.8 for 2 factors, 7.4 for 3 factors, 14.1 for 4 factors, and 27.1 for all 5 risk factors combined. CONCLUSIONS: Five risk factors for growth of small choroidal melanocytic tumors have been identified. The combinations of various factors increase the risk for tumor growth from 4% if no factors are present to more than 50% if 3 or more risk factors are present. These factors may be important when counseling patients with small suspicious choroidal melanocytic tumors.
BACKGROUND & AIMS: Celiac disease is a gluten-induced enteropathy characterized by the presence of gliadin-specific CD4(+) T cells in the lamina propria and by a prominent intraepithelial T-cell infiltration of unknown mechanism. The aim of this study was to characterize the subset(s) of intraepithelial lymphocytes (IELs) expanding during active celiac disease to provide insights into the mechanisms involved in their expansion. METHODS: Flow-cytometric analysis of isolated IELs and/or immunohistochemical staining of frozen sections were performed in 51 celiac patients and 50 controls with a panel of monoclonal antibodies against T-cell and natural killer (NK) receptors. In addition, in vitro studies were performed to identify candidate stimuli for NK receptor expression. RESULTS: In normal intestine, different proportions of IELs, which were mainly T cells, expressed the NK receptors CD94/NKG2, NKR-P1A, KIR2D/3D, NKp46, Pen5, or CD56. During the active phase of celiac disease, the frequency of CD94(+) IELs, which were mostly alphabeta T cells, was conspicuously increased over controls. In contrast, the expression of other NK markers was not modified. Furthermore, expression of CD94 could be selectively induced in vitro by T-cell receptor activation and/or interleukin 15, a cytokine produced by intestinal epithelial cells. CONCLUSIONS: The gut epithelium favors the development of T cells that express NK receptors. In active celiac disease, there is a specific and selective increase of IELs expressing CD94, the HLA-E-specific NK receptor that may be related to T-cell receptor activation and/or interleukin 15 secretion.
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We evaluated, through Doppler echocardiography, left ventricular (LV) mass and function in 82 obese young women (aged <40 years) who were asymptomatic, without any cardiovascular or pulmonary disease compared with a lean control group matched by age and height. LV mass, LV mass/height, and LV mass/volume were increased in obese women, and a lower LV E- and A-wave velocity ratio was noted, suggesting early cardiac involvement.
The aim of this study was to examine antigen-induced lung cell migration, eosinophil activation, and pulmonary reactivity of Wistar rats exposed to a new sensitization technique. The animals were sensitized with a single subcutaneous implant of a fragment of heat coagulated hen egg white and challenged 21 days later with an intratracheal injection of heat-aggregated ovalbumin (EWI). For comparison, another group of rats were sensitized by an intraperitoneal injection of ovalbumin in alum as adjuvant, with one booster on day 14 and challenge on day 21 post immunization (OVA/AL). Twenty-four hours after antigen challenge, the EWI group presented a higher number of eosinophils in the bronchoalveolar lavage (BAL) (4.85 +/- 1.43 x 10(6)) than the OVA/AL group (0.2 +/- 0.06 x 10(6)) or the control group, where the level of eosinophils were essentially undetectable. Levels of eosinophil peroxidase activity were increased in the cell-free BAL and homogenates of lung tissue in the EWI group (12.10 +/- 2.97 mg/mL and 36.14 +/- 7.21 ng/mg, respectively), but not in the OVA/AL group (4.83 +/- 1.4 ng/mL and 11.95 +/- 2.54 ng/mg, respectively), as compared with controls (5.16 +/- 1.65 ng/mL and 12.13 +/- 1.74 ng/mg, respectively). Thromboxane B2 levels were also increased in the BAL of EWI group (2.89 +/- 0.54 ng/mL) but not the OVA/AL group (1.13 +/- 0.23 ng/mL) as compared with controls (1.14 +/- 0.19 ng/mL). In contrast, the levels of prostaglandin E2 in the BAL were increased in both groups (456.4 +/- 11.8 pg/mL in the EWI group and 303.5 +/- 31.7 pg/mL in the OVA/AL group) as compared with controls (205.7 +/- 29.7 ng/mL). Moreover, only the EWI group developed increased pulmonary reactivity to serotonin (around two-fold), 24 hours after antigen challenge. The extent of lung eosinophil migration and activation and the pulmonary hyperreactivity induced by this novel sensitization procedure without adjuvants represents a significant improvement over existing experimental models of asthma.
OBJECTIVE: The practice patterns of international medical graduate (IMG) and U.S. medical graduate (USMG) psychiatrists were compared. METHOD: Using data from the 1996 National Survey of Psychiatric Practice, the authors compared IMGs and USMGs in terms of demographic characteristics, practice settings, patients' clinical characteristics, and sources of reimbursement. RESULTS: The IMGs surveyed tended to be older than USMGs, included a higher proportion of women, and were more racially heterogeneous. They worked longer hours, worked more frequently in the public sector, and treated a higher proportion of patients with psychotic disorders. The IMGs also received a higher percentage of their income than USMGs from Medicaid and Medicare, whereas the reverse was true of self-payment. Most of these differences remained significant after psychiatrist's age, gender, race, board certification, and work setting were controlled for. CONCLUSIONS: IMG and USMG psychiatrists have different practice patterns. Policies that substantially decrease the number of IMG psychiatrists may adversely affect the availability of psychiatrists to treat minorities and other underserved populations.
OBJECTIVE: To evaluate cardiac involvement in children with metabolic disease in the out patient clinic of the Pediatric Cardiology Unit of Maria Pia Children's Hospital and their follow-up. MATERIAL AND METHODS: Twenty-nine medical records belonging to out patients with metabolic disease in consultation at our unit were reviewed. The following data from each record was analyzed: sex, metabolic disease diagnosis, age and motive for referral to a pediatric cardiology unit, cardiology diagnosis, therapy and evolution. RESULTS: Seventeen patients were boys and 12 girls. The average age of referral was 7.2 years (SD 4.8). The motives for referral were: screening for heart disease, 16; heart murmur, 7; congestive heart failure, 3; heart murmur and fatigue, 2; poor weight gain, 1. The following metabolic diagnoses were made: lysosomal diseases, 21; mitochondrial citopathies, 5; disorder of beta-oxidation of fatty acids, 2; carbohydrate deficient glycoprotein syndrome (CDG syndrome), 1. The cardiologic evaluation was normal in ten patients (4 with lysosomal disease, 4 with mitochondrial citopathy, one disorder of beta-oxidation of fatty acids, the CDG syndrome). Mitral and aortic valve lesions predominated in lysosomal diseases (12/21); myocardial involvement alone was present in two patients, and both myocardial and valvular lesions were present in three. Dilated cardiomyopathy was the presented manifestation in two patients-one with mitochondrial citopathy and one with a disorder of beta-oxidation of fatty acids. Three patients died and 26 remain out-patients. One patient was submitted to valve surgery. The average duration of follow-up was 21 months (SD 24). COMMENTS: Lysosomal diseases were the most representative in our patients, as described in the literature. Heart valve disease was the most frequent alteration. Indication for heart valve surgery is dependent on systemic involvement of the primary disease. All children with a metabolic disease with eventual heart involvement should be evaluated periodically by a cardiology unit. On the other hand, it is mandatory to screen a cardiomyopathy of unknown cause for a metabolic disease. The authors draw attention to the importance of infectious endocarditis prophylaxis in this group of patients.
An increased spatial dispersion of ventricular repolarization duration (QT dispersion) is associated with an increased vulnerability to arrhythmias. This study was designed to examine the effect of exercise on QT dispersion in ischemic heart disease (IHD). QT dispersion, corrected QT dispersion, and percentage change in uncorrected and corrected QT dispersion between rest and peak exercise were examined in 14 members of a control group, 17 patients with IHD, and 14 patients with IHD who were receiving beta-blockers (IHD-B). All subjects had undergone a standard Bruce protocol exercise test, and QT intervals were measured at rest and peak exercise with a digitizing tablet interfaced to a personal computer. QT dispersion at rest was markedly increased in the IHD group compared with that in the control and IHD-B groups, respectively (corrected QT dispersion in milliseconds), 74 +/- 7, 40 +/- 4, 49 +/- 5, p < 0.03). The corrected QT dispersion at peak exercise was greater in the IHD group compared with that in the control group (57 +/- 5 vs 26 +/- 3 msec, p < 0.03). The percentage change in QT dispersion with exercise was significantly higher in the IHD group (52% +/- 5%) compared with that in both the control group (28% +/- 4%, p < 0.002) and the IHD-B group (30% +/- 3%, p < 0.01). A larger mean QT dispersion at peak exercise and an increased percentage change in QT dispersion with exercise may help explain the increased susceptibility of the IHD group for arrhythmias. The cardioprotective action of beta-blockers may be explained by their blunting effect on exercise-related changes in QT dispersion.
The L-type voltage sensitive calcium channels (VSCC) of chick embryo retinospheroids were characterized during the development in vitro. Functionally, the activity of VSCC was characterized by continuously monitoring the changes in the intracellular free Ca2+ concentration (delta[Ca2+]i) with indo-1, in response to 30 mM KCl. The contribution of the L-type VSCC was evaluated using the L-type VSCC antagonist, nitrendipine. We also characterized the binding of [3H]nitrendipine to retinospheroid membranes during development, and determined the Kd and Bmax values. We observed that the changes in [Ca2+]i in response to 30 mM KCl increased from 159.46 +/- 6.62 nM at 0 days in vitro (DIV) retinospheroids to 704.4 +/- 59.9 nM at 14 DIV retinospheroids. Nitrendipine (2 microM) blocked the delta[Ca2+]i response by approximately 67% in all ages tested. No significant difference in the Kd values for the nitrendipine binding was observed during in vitro development of the retinospheroids. However, the Bmax increased from 27.99 +/- 1.95 fmol/mg protein in 0 DIV retinospheroids to 131.09 +/- 14.24 fmol/mg protein in 14 DIV retinospheroids, supporting the delta[Ca2+]i results. The results presented suggest that the increase in [Ca2+]i during development was due to an increase in the number of L-type channels. Therefore, the expression of L-type VSCC is developmentally regulated during retinogenesis in vitro and accompanies neuronal maturation, probably regulating the Ca2+ input crucial to the onset of important intracellular Ca2+-dependent functions.
Independent lung ventilation with two ventilators is sometimes used in the management of bronchopleural fistula (BPF). We describe a patient in whom gas flow through a large BPF was initially reduced, and subsequently eliminated, during differential lung ventilation using a single ventilator and a variable-resistance valve attached to one lumen of a bifurcated endotracheal tube.
At present several lines of evidence indicate that the nucleus is functionally compartmentalized into discrete structures with defined properties. For instance, it is well established that the molecular machines involved in replication, transcription, and RNA processing assemble into morphological entities but it remains unclear whether these correspond to autonomous "organelles" or rather represent temporary accumulations of either active factors recruited onto DNA templates or inactive factors stored in the vicinity of genes. According to the latter view, the spatial distribution of genes during interphase should play a major role in the subnuclear organization of nonchromatin components such as replication, transcription, and processing factors, and in this article we discuss current ideas on the functional compartmentalization of chromosomes and genes within the nucleus.
Short-term cultures from an alveolar adenoma of the lung were cytogenetically examined. Of the 54 metaphases studied, 44 were characterized by an apparently normal karyotype and 10 showed a pseudodiploid karyotype: 46,XX,add(16)(q24). Fluorescence in situ hybridization studies permitted identification of the add(16)(q24) as a der(16)t(10;16)(q23;q24). This is the first report of a chromosomal aberration in an alveolar adenoma of the lung.
In the present study we analyzed the effect of ascorbate (0.8 mM)/Fe2+ (2.5 microM)-induced membrane lipid peroxidation on the levels of intracellular free calcium,[Ca2+]i and on the possible mechanisms involved in the perturbation of intracellular calcium homeostasis during oxidative stress. For this purpose, the influence of the ascorbate/iron oxidant system on the plasma membrane and endoplasmic reticulum Ca(2+)-dependent ATPases of brain cortical synaptosomes was studied. In addition, the influence of the peroxidative process on the uptake of calcium (45Ca2+) and on the Na+/Ca2+ exchange activity at the plasma membrane was evaluated. After ascorbate/Fe(2+)-induced membrane lipid peroxidation of the order of 18.05 +/- 4.20 nmol TBARS/mg protein, an increase in [Ca2+]i occurred, under basal or depolarizing conditions (30 mM KCl), which was dependent on the extracellular calcium concentration. Thus, for 1 and 3 mM extracellular calcium concentration, an increase of the resting [Ca2+]i values of 19.8% and 33.7% was observed, while after the K(+)-depolarization the enhancement of the [Ca2+]i was 18.4% and 29.5%, respectively. The Na+/Ca2+ exchange activity and the time-dependent influx of 45Ca2+ observed in basal conditions and after the 30 mM K(+)-depolarization, were not affected under the peroxidative conditions. The Ca(2+)-dependent ATPase activity of the synaptosomal plasma membrane was significantly depressed following peroxidation of membrane lipids, decreasing the V(max) by 48.1%, without significant changes in the affinity of the enzyme for calcium (K(m) for Ca2+ was 0.54 +/- 0.04 microM in control conditions and 0.56 +/- 0.034 microM in peroxidized conditions). The Ca(2+)-ATPase activity of the endoplasmic reticulum was also affected during ascorbate/iron-induced oxidative stress; thus, an inhibition of 45.2% was observed 5 min after adding ATP. These data suggest that the increase in synaptosomal [Ca2+]i due to oxidative stress may result from the inhibition of the plasma membrane and the endoplasmic reticulum membrane Ca(2+)-ATPase activities, probably as a result of the alteration of the lipid environment required for the maximal activity of these membrane enzymes. The consequent increase in [Ca2+]i may be responsible for the injury of the nervous tissue observed during several pathological conditions in which free radical generation seems to be involved.
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During a multicenter surveillance study on Streptococcus pneumoniae resistant to antibiotics in Portugal we have analyzed, within the predominant serotypes of penicillin G resistant strains, the chromosomal DNA restriction profiles by pulsed field gel electrophoresis. The aim of this work was to compare the PFGE restriction profiles of penicillin resistant pneumococci isolated in France with those of Portuguese strains within each serotype. We have studied fifteen penicillin resistant strains isolated in different geographical regions of France, and representing equally the three predominant resistant serotypes 23F, 9V and 14. In general we observed an important homogeneity of profiles within each serotype, in the two countries. In serotype 23F, the five French strains studied show subtypes of a pattern called A, also detected in the majority of 23F Portuguese strains; similarly 4 of the 5 serotype 9V strains belong to subtypes of the pattern G, also common within 9V Portuguese strains; 4 of the 5 strains of serotype 14 show a subtype of profile H, found often in Portuguese strains. The observed homogeneity of chromosomal DNA restriction profiles within each serotype in the two countries, confirms the importance of geographic spread of pneumococcal resistant clones, previously described.
An interphase cytogenetics analysis was performed to investigate whether replication and transcription could influence in situ resolution of immunoglobulin (Ig) heavy chain constant region genes. A plasmid probe recognizing five C gamma segments separated by known linear DNA distances was hybridized in situ and visualized by digital fluorescence microscopy. In interphase nuclei from phytohemagglutinin (PHA)-stimulated lymphocytes, the gamma genes were resolved as one to three signals per allele in the majority of nuclei, whereas in a minority, complex patterns of several signals per allele could be observed. The latter were restricted to nuclei in an early stage of the S phase, as assessed by hybridization experiments performed in cells grown in the presence of bromodeoxyuridine. To investigate whether the in situ resolution of the C gamma segments could vary as a function of the transcription activity of the locus, the C gamma probe was subsequently hybridized to nuclei from a mature B cell line (JVM-2), which produces gamma transcripts as shown by in situ RNA hybridization experiments. Primary human fibroblasts were further used as representative of a non-lymphoid cell type with transcriptionally inactive Ig genes. When Gl nuclei from the three cell types were compared in terms of the in situ resolution of the C gamma locus, JVM-2 cells were found to include the highest percentage of higher resolution patterns (three to five signals per allele in 28% of nuclei), fibroblasts the lowest (three signals per allele, 2%), while PHA-stimulated lymphocytes occupied an intermediate position between the other two cell types (three or four signals per allele, 15%). The data show that the in situ resolution of Ig C gamma genes varies throughout the cell cycle and is influenced by the transcriptional activity of the locus. The variability of the resolution patterns observed appears to reflect different levels of chromatin packaging, which in turn are likely to influence the probe accessibility to its target. These observations are relevant for the interpretation of data from interphase cytogenetics analysis of independent, but closely spaced, DNA segments.
Aims-To directly visualise immunoglobulin (Ig) heavy (H) and light chain genes (kappa and lambda) in metaphase chromosomes and interphase nuclei of normal and malignant lymphocytes using small genomic probes targeted to intragenic sequences.Methods-Cytogenetic preparations from phytohaemagglutinin stimulated lymphocytes, B-chronic lymphocytic leukaemia (B-CLL) cells, and a B-prolymphocytic leukaemia (B-PLL) cell line, containing a t(11;14), were hybridised in situ using biotin or digoxigenin labelled plasmid probes. The kappa genes were visualised with a combination of probes for the Ckappa, Jkappa, Vkappa1, and Vkappa2 segments, the lambda genes with a probe containing the Jlambda2-Clambda2, Jlambda3-Clambda3 segments and the H genes with a probe for Clambda2. Hybridisation sites were visualised using appropriate fluorochrome conjugates and images were analysed by digital microscopy.Results-In both normal and malignant lymphoid cells, the kappa and lambda genes were visualised as a single dot signal, whereas the H lambda genes were resolved as either two or three separate signals per chromatid in metaphase chromosomes or per allele in interphase nuclei. In the malignant PLL cells, double hybridisation experiments with a painting library specific for the chromosome 11 showed that the lambda region was retained in the translocated chromosome, with an in situ resolution pattern similar to that of the normal allele.Conclusions-This study shows that a high resolution in situ analysis of the three Ig loci can be efficiently performed with small size genomic probes on both normal and malignant lymphoid cells. Such an approach offers a flexible tool for the molecular characterisations of these loci on chromosomes and individual neoplastic cells.