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Biomedical subjects

C Leal

Publications and source records attributed to C Leal.

At least 19 recordsLinked to original sources

Persistent auditory hallucinations.

BACKGROUND: There is still a significant proportion of psychotic patients who suffer from persistent auditory hallucinations (PAH) in spite of treatment. The objective of our study was to analyze those clinical dimensions that characterize persistent hallucinators in comparison with episodic hallucinators. SAMPLING AND METHODS: Ninety-one outpatients with AH were assessed through semistructured interviews. The interviews included the Psychotic Symptom Rating Scales for AH and the Krawiecka scale. They elicited descriptions about the persistence of AH, existence of pleasurable hallucinations and other types of hallucinations. RESULTS: Forty-five patients fulfilled criteria for reported PAH. Persistent hallucinators showed greater scores in frequency and duration of hallucinations, Krawiecka total score and incoherence of speech. Moreover, pleasurable experiences were more frequent in this group of patients. Logistic regression analysis rendered a model with the following variables: duration of voices, degree of control and pleasurable hallucinations. CONCLUSION: Specific dimensions of AH can predict the possibility of treatment resistance.

Adult↗

Simultaneous itraconazole bioequivalence assessment and CYP3A phenotyping in South American subjects.

OBJECTIVE: The present study evaluates the acute effect of a single-dose itraconazole administration on CYP3A phenotype, as measured by cortisol MR ratio in urine. METHODS: Twenty-four healthy Uruguayan subjects recruited according to strict inclusion criteria participated in an open-label, randomized, two-period, crossover study designed to evaluate the bioequivalence of an itraconazole formulation (Traconal 100 mg, Achê Labs, São Paulo, Brazil). The study comprised two treatment periods separated by a wash-out period of 14 days. In each period a series of venous blood samples were drawn over 48 hours. Three urine samples were obtained for CYP3A phenotyping: pre-dose, 24 and 48 hours after dosing. Blood and urine samples were assayed for itraconazole, beta-hydroxycortisol and cortisol using a validated chromatographic method. RESULTS: The ratio of the mean AUC0-inf. T/AUC0-inf. R was included in the bioequivalence range, however, due to high variability, the CI90% was not. It was found that the cortisol metabolic ratio (MR) showed inhibition relative to basal activity in a proportion of subjects 24 hours (68 +/- 6.1%, mean +/- CI95%) and 48 hours (80 +/- 7.3%, mean +/- CI95%) after ingestion of itraconazole. A significant correlation was found between itraconazole AUC0-inf. and normalized basal CYP3A MR for the reference (r = 0.62, t = 3.72, p = 0.001) and the test product (r = 0.74, t = 5.22, p = 0.00003). A good correlation existed between basal cortisol MR and the elimination half-life of itraconazole. CONCLUSIONS: The findings are in line with the hypothesis that the determination of the bioavailability of highly variable CYP3A substrates might be improved by simultaneous non-interfering phenotyping. If this is confirmed, a new methodological paradigm may need to be developed in order to take account of metabolic variability in bioequivalence evaluation of this group of drugs.

Adolescent↗

A possible association between the CCK-AR gene and persistent auditory hallucinations in schizophrenia.

Recent studies have suggested that DNA variations in the CCK-AR gene might predispose individuals to schizophrenia and particularly to auditory hallucinations (AH). The aim of this study is to assess the association between AH, using a specific scale for AH in schizophrenia (PSYRATS), and the CCK-AR polymorphism at 779 in a Spanish sample. A total of 105 DSM-IV schizophrenic patients with AH and 93 unrelated controls were studied. Twenty-two patients were considered as persistent auditory hallucinators, which showed similar clinical and demographic characteristic than patients with episodic AH, but with the exception of the PSYRATS values. The persistent AH group showed an excess of the A1 allele when was compared with episodic or control groups. Our data support the possible role of the CCK-AR gene in the development of persistent AH in schizophrenic patients.

Adult↗

Pleasurable auditory hallucinations.

OBJECTIVE: The focus in auditory hallucination (AH) research is usually on the negative impact of the experience itself. There are practically no studies on whether voices can be perceived as pleasurable. The aim of the present study was to assess the frequency of voices as a pleasurable experience in a psychotic patient population. METHOD: A total of 160 patients with AHs (89 schizophrenia and 17 other psychoses) were assessed with the psychotic symptom rating scale (PSYRATS) for AHs, including an added item on whether the experience was pleasurable. RESULTS: Twenty-eight patients (26%) reported the voices as a pleasurable experience and 10 of them did so frequently. Pleasurable hallucinations showed negative associations with amount and intensity of distress, degree of negative content and loudness. Positive associations were apparent with chronicity and perceived control over the voices. CONCLUSION: Pleasurable hallucinations can be detected in a substantial proportion of patients, and cross validated with existing instruments.

Adult↗

Similar effect of family history of psychosis on Sylvian fissure size and auditory P200 amplitude in schizophrenic and bipolar subjects.

Several cerebral studies point to the non-specificity of structural and functional changes described in schizophrenia and bipolar disorders. Furthermore, the origin of these changes is still unclear. The present study investigated the effect of a family history (FH) of psychotic disorders in first-degree relatives on computed tomographic (CT) measures (ventricular, cerebral and Sylvian fissure size) and auditory event-related potentials (amplitudes and latencies of peak components in oddball paradigms) in 30 schizophrenic patients and 24 bipolar type I patients. We found a significant correlation between FH and the size of the right Sylvian fissure, and between FH and auditory P200 amplitude. More specifically, the schizophrenic and bipolar patients with negative FH (n=36) had larger right Sylvian fissures and smaller P200 amplitude than patients with positive FH (n=18). These findings were independent of the specific diagnosis, gender, and age of subjects. Our results suggest some underlying process common to schizophrenia and bipolar I disorder, and they provide support for the continuum view of the nosologic structure of psychotic illness.

Adolescent↗

Determination of macrolide antibiotics by liquid chromatography.

The liquid chromatographic separation of seven macrolides used in food producing animals in the European Union has been studied. Separation was performed by using an end-capped high-purity silica-based C18 column and mobile phases consisting of phosphate buffer (pH 2.5)-acetonitrile mixtures. The effect of pH and acetonitrile percentage on the separation was examined. Two UV-based detection systems, wavelength programming and diode array, were assayed. Detection limits were in the range 6-33 microg l(-1) for spiramycin, tilmicosin, tylosin, kitasamicin and josamicin and about 400 microg l(-1) for erythromycin and oleandomycin. The suitability of the method for multiresidue determination of the five macrolides is demonstrated by the analysis of spiked samples of chicken muscle.

Anti-Bacterial Agents↗

Blood flow rate and energy charge in the isolated perfused canine liver.

Background. Liver viability depends on blood flow rate, which varies among isolated perfused livers used in different studies. We aimed to identify the minimal blood flow capable of keeping the energy charge compatible with liver viability. Materials and methods. Isolated canine livers were assigned to different groups (n = 4) with blood flow rates of 0.5 (Group I), 1.0 (Group II), and 1.5 ml/g/min (Group III). Blood gases, hematocrit, and glucose were measured over 180 min. Nucleotides, serum osmolarity, and electrolytes were also measured. Morphological changes were recorded at the end of each experiment. Results. Acid-base balance was better in livers from Group III. Electrolytes, osmolarity, hematocrit, and glucose showed no differences. Higher energy charges correlated with higher blood flow rates. On histopathology, there was evidence of more hydrostatic pressure-related changes in Group III, with no difference in necrosis or inflammatory-related alterations. Conclusions. (1) Energy charge correlates strongly with blood flow rate. (2) A rate of 1.5 ml/g/min allows for a better electrolyte, osmolarity, and acid-base balance. (3) Morphological analysis is not a sensitive predictor of organ viability as assessed by energetic potential. (4) The minimal blood flow rate required to attain an energy charge above 0.75 is 1.33 ml/g/min.

Acid-Base Equilibrium↗

Effect of exogenous melatonin on hepatic energetic status during ischemia/reperfusion: possible role of tumor necrosis factor-alpha and nitric oxide.

BACKGROUND: This study was designed to determine if the very potent antioxidant melatonin is able to reduce organ damage and improve energetic status in an in situ liver ischemia/reperfusion model. MATERIALS AND METHODS: Total hepatic ischemia was induced in rats by occlusion of the hepatic artery, portal vein, and bile duct. A portojugular shunt was inserted. After 60 min of ischemia, reperfusion was established for a period of 120 min. Rats were assigned to one group receiving systemic melatonin administration or to another receiving only normal saline. Variables were observed at preischemia, after 60 min of ischemia, and at 30, 60, and 120 min of reperfusion. RESULTS: Energy charge, measured as the arterial ketone body ratio, showed higher values in the melatonin group during the first 60 min of reperfusion. Rises in plasma nitrite, tumor necrosis factor (TNF)-alpha, aspartate aminotransferase, alanine aminotransferase, lipid peroxidation products, and inducible nitric oxide synthase (iNOS) expression were less severe with melatonin. Linear regression analysis demonstrated a significant correlation between nitrites and arterial ketone body ratio (R(2) = 0.2454). Bile production was higher with melatonin. Seven-day survival rates were 52% for control, 80% for melatonin, and 100% for sham groups. CONCLUSIONS: Exogenous melatonin is capable of preserving the functional and energetic status during ischemia/reperfusion which is associated with reduced concentrations of TNF-alpha and inhibited expression of iNOS and NO production. This improvement may be due to an adequate preservation of the hepatic mitochondrial redox status.

3-Hydroxybutyric Acid↗

Alterations of cell cycle regulators affecting the RB pathway in nonfamilial retinoblastoma.

We undertook the present study to examine alterations affecting the RB pathway in the G1 checkpoint and to determine their potential clinical significance in children affected with nonfamilial retinoblastoma. Using immunohistochemistry, patterns of expression of pRB, p16/INK4A, and E2F1 were analyzed in tissue from a cohort of 86 well-characterized patients with nonfamilial retinoblastoma diagnosed at the "Instituto Nacional de Pediatria" in Mexico City. The relationship of these phenotypes to proliferative index was assessed by analysis of Ki67 antigen expression. pRB expression was found in 11 (13%) cases. Using a hypophosphorylated specific pRB antibody, we observed low levels of underphosphorylated pRB expression in only 1 of 9 evaluable positive cases. These data suggest that the detected pRB products were hyperphosphorylated and thus had decreased functional activity. Increased p16 nuclear expression was found in only 6 tumors. No tumors showed deletions or mobility shifts of the INK4A gene. Undetectable pRB levels were significantly associated with undetectable p16 expression (odds ratio, 10.8; 95% confidence interval, 1.4-81.3; P =.03). All tumors showed nuclear immunoreactivities for E2F1 and Ki67. Increased Ki67 proliferative index was associated with increased staining for E2F1 (r =.44; P =.008) and increasing clinical stage (P =.03). Among children with unilateral disease, the mean Ki67 proliferative index was significantly higher in children with advanced clinical disease (stages 3 and 4) (mean 81.25; SD 6.78) than in those with earlier stage disease (mean 69.50; SD 9.45) (P = 0.001). Among children with bilateral disease, however, the mean proliferative index was not significantly higher for children with advanced clinical stage. When examining all cases together, there was a significant trend toward increasing proliferative index with increasing clinical stage (P =.03). In unilateral tumors, we also found that presence of detectable pRB was associated with a lower percentage of cells expressing E2F1 (46.7% v 70.8%) (P = 0.05), whereas there was no association between presence of pRB and E2F1 among bilateral tumors. We have found that expression of some of the cell cycle markers examined varies according to laterality, suggesting underlying differences in the capacity for cell cycle regulation between these 2 forms of the disease. Differences in capacities for cell cycle regulation may account for some differences in clinical behavior. Thus, the inclusion of molecular markers may become useful adjuncts to clinicopathological staging and subsequent determination of therapy.

Age Factors↗

Apocrine ductal carcinoma in situ of the breast: histologic classification and expression of biologic markers.

Apocrine ductal carcinoma in situ (ADCIS) has been called a special type of ductal carcinoma in situ (DCIS) because the histologic grading is considered difficult using the classification schemes that have been proposed for common DCIS. However, ADCIS encompasses a spectrum of lesions with different morphologic aspects ranging from minimally atypical to overtly malignant. To define a classification scheme for ADCIS, 35 cases (22 pure and 13 associated with invasive carcinoma) were selected on the basis of conventional morphology on hematoxylin and eosin (H&E)-stained sections. Each case was assigned to 1 of 3 histologic grades (low, intermediate, and high) based on nuclear morphology and the presence of necrosis. In addition, the expression of hormone receptors p53, bcl-2, c-erbB-2, and Ki-67 was evaluated by immunohistochemistry, and the DNA ploidy was determined by image cytometry. Fifteen cases were classified as high histologic grade, 10 as low histologic grade, and the other 10 as intermediate grade. All but 4 cases, irrespective of grade, had the same hormonal immunophenotype: androgen receptor positivity (97.1%) and estrogen receptor and progesterone receptor negativity (94.3% and 97.1% respectively). Twenty-one cases (61.8%) showed p53 expression, and 47.1% of the cases were positive for c-erbB-2. The median positivity for Ki-67 was 5.2%. ADCIS has a unique morphologic and hormonal profile, distinct from common DCIS, deserving a specific classification. The proposed classification scheme allows for categorization of ADCIS according to the most important morphologic features already seen in common DCIS, ie, nuclear grade and necrosis. The expression of biologic markers other than hormonal receptors and bcl2 in ADCIS seems in general to be similar to that in common DCIS. Ki-67 and c-erbB-2 are expressed more frequently in intermediate and high histologic grade ADCIS.

Adult↗

Squamous cell carcinoma of the breast.

Squamous carcinoma of the breast (SCB) is a rare entity. For its diagnosis, the exclusion of squamous cell carcinoma of local cutaneous structures and metastasis of distant squamous carcinoma are mandatory. The aim was to retrospectively evaluate the prevalence, epidemiological and clinical characteristics of the cases of SCB, studied in our institution, between January 1985 and December 1996. The diagnosis was histopathological. We studied the patients' demographic data and tumour characteristics. In the 11-year study period, 5791 patients with breast carcinoma were admitted to our Institution, seven (0.1%) of which were SCB. All seven patients were female and Caucasian. Their average age was 63 years (range 24-82). The presentation was always a breast lump. Five patients were in Stage II-A and two in Stage II-B. All tumours were hormone-receptor negative. The initial treatment was surgery and four patients received adjuvant radiotherapy. The median follow-up was 64 months. No relapses were diagnosed. SCB is a rare entity. The initial therapeutic approach should be surgical. There is still no consensus regarding adjuvant therapy. The prognosis of this type of breast cancer is still the subject of controversy with some series, including the present study, suggesting an indolent clinical course and a relatively good prognosis.

Journal Article↗

A comparison of oral ondansetron syrup or intravenous ondansetron loading dose regimens given in combination with dexamethasone for the prevention of nausea and emesis in pediatric and adolescent patients receiving moderately/highly emetogenic chemotherapy.

This double-blind, parallel-group, multicenter study compared the efficacy and safety of intravenous (i.v.) ondansetron with oral syrup ondansetron plus oral dexamethasone in the prevention of nausea and emesis in pediatric patients receiving moderately/highly emetogenic chemotherapy. On each day of chemotherapy, patients were administered ondansetron 5 mg/m2 i.v. and placebo syrup orally (n = 215) or ondansetron 8 mg syrup orally and placebo i.v. (n = 223) plus dexamethasone 2-4 mg p.o. Ondansetron 4 mg syrup p.o. was administered twice daily for 2 days following the cessation of chemotherapy. Complete or major control of emesis was obtained in 89% patients in the i.v. group and 88% patients in the oral syrup group during the worst day of chemotherapy treatment (90% CI: -6, 4) and in 85% and 82% patients, respectively, during the worst day of the study period (90% CI: -8, 3). Intravenous or oral syrup ondansetron plus dexamethasone was well tolerated and effective in preventing chemotherapy-induced emesis in pediatric patients.

Administration, Oral↗

Presence of human papilloma virus in tumor tissue from children with retinoblastoma: an alternative mechanism for tumor development.

Epidemiological studies have shown that the use of barrier methods of contraception is associated with a decreased incidence of papilloma virus infection and reduced risk of having a child with retinoblastoma. Thirty-nine primary retinoblastomas were analyzed for the presence of papilloma virus sequences. Tumor tissue sections were also used to assess the expression of the retinoblastoma protein and proliferative index. Papilloma sequences were detected in 14 of 39 (36%) tumors. Tumors in which viral sequences were detected were associated with a lower proliferative index (68% versus 78%; P = 0.015). Children with tumors containing viral sequences had a lower risk of extraocular disease (odds ratio, 9.0; 95% confidence interval, 1.6-49; P = 0.008) and a lower birth weight (2.9 versus 3.5 kg; P = 0.030). Based on these data, it is our hypothesis that papilloma viruses may play a role in the development of sporadic retinoblastoma. Detection of papilloma virus sequences and retinoblastoma protein in certain primary lesions suggests an alternative mechanism of tumor development for sporadic retinoblastoma.

Age of Onset↗

Liquid chromatography with fluorimetric detection of triorganotin compounds in marine biological materials.

Several extraction methods have been evaluated for marine biological materials with regard to tributyltin and triphenyltin determination by liquid chromatography with post-column fluorimetric detection using fisetin as a fluorogenic reagent. Extraction with ethyl acetate in a hydrochloric acid medium has been shown to be the most appropriate extraction method and it has been successfully applied to fish (sea bass) reference material from the National Institute for Environmental Studies (NIES-11) and to a candidate reference material.

Animals↗

Intracystic (encysted) papillary carcinoma of the breast: a clinical, pathological, and immunohistochemical study.

Intracystic papillary carcinoma (IPC) of the breast is a rare tumor with predilection for elderly women and distinctive pathological features that must be distinguished from ductal carcinoma in situ (DCIS) of papillary type and from invasive papillary carcinoma. The clinical, radiological, and pathological features of 29 cases of IPC are reported. The cases were divided into three groups (IPC alone, associated with DCIS, or associated with invasive carcinoma) and studied in terms of their size, predominant architectural pattern, nuclear grade, and presence of necrosis. Immunohistochemical studies were performed to evaluate the c-erbB2 oncoprotein, estrogen receptors, and ki-67 antigen expression. The median age of the patients was 75 years. Microscopically, nine tumors (31.0%) were IPC alone, nine (31.0%) had IPC associated with DCIS, and 11 (38.0%) were IPC associated with invasive carcinoma. Most of the IPC cases had low or intermediate nuclear grade, no necrosis, strongly expressed estrogen receptor, and was negative for c-erbB-2. Nuclear grade 3 and necrosis were found only in cases of IPC associated with invasive carcinoma. The median Ki-67 antigen expression was 10.6%. One patient with IPC alone had a recurrence 5 years later. Lymph node metastases were found in one patient who had the tumor with the biggest invasive area. IPC is a low-grade carcinoma with overall good prognosis. However, there is a high frequency of DCIS or invasive carcinoma associated with it, and the prognosis of these cases is related to the type, grade, and size of the associated lesions.

Aged↗