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Biomedical subjects

J Serrano

Publications and source records attributed to J Serrano.

At least 91 records · Page 5Linked to original sources
PubMed1999

Valproate population pharmacokinetics in children.

OBJECTIVE: A population analysis of the kinetics of valproic acid (VPA) in children with epilepsy was performed in order to characterize the covariates which influence VPA clearance (CL). METHODS: A total of 770 steady-state serum concentration samples was analysed. These were collected during VPA therapy from 255 children, aged 0.1-14 years and weighting 4-74 kg. Age, total body weight (TBW), VPA daily dose, sex and comedication with carbamazepine (CBZ) were considered as covariates. Population analysis was made with NONMEM program, assuming a one-compartment model, fixing the VPA absorption rate, bioavailability and distribution volume at values found in the literature. The results of the population pharmacokinetics analysis were validated in a group of 45 epileptic patients. RESULTS: The final regression model for VPA clearance, that included TBW (kg), daily dose (mg/kg) and CBZ comedication as covariates with a significant influence on this parameter, was as follows: CL (L/h) = 0.012 TBW0.715 DOSE0.306(1.359 CBZ). The coefficient of variation for interpatient variability in CL was 21.4% and the residual variability estimated was 23.9% for a concentration of 65 mg/l. In order to estimate the predictive performance of the selected final model, predictions of the VPA serum concentrations were calculated and compared with VPA measured concentrations in the validation group. This assessment revealed an important improvement in the predictive performance of VPA concentrations in comparison with the basic model that did not include any covariates (root squared mean error: 19.50 vs. 39.73 mg/l). CONCLUSION: A population pharmacokinetic model is proposed to estimate the individual CL for paediatric patients receiving VPA in terms of patient's dose, weight and concomitant CBZ, in order to establish a priori dosage regimens.

Adolescent↗
PubMed1999

Ultrastructural identification of small granule prolactin (PRL) cells in goat adenohypophysis by the colloidal-gold method.

We describe ultrastructural characteristics of PRL cells with small secretory granules, immunostained with ovine antiserum, in adult Murciano-Granadina milking goats during anoestrus, the last third of gestation and lactation. This cell subtype is considered to comprise a stable population that decreases numerically during gestation and lactation, and that may change during these stages to show large granules.

Anestrus↗
PubMed1999

Planar scintigraphy and SPET with 99Tcm-HMPAO-labelled leukocytes in patients with median sternotomy: normal patterns.

The aim of this study was to determine the normal planar and SPET patterns of the thoracic distribution of 99Tcm-hexamethylpropylene amine oxime (99Tcm-HMPAO) in 20 patients who had undergone a previous median sternotomy and without infectious complications at follow-up. The study included anterior and oblique anterior planar views at 4 and 20 h. SPET of the chest was also carried out at 4 and 20 h. At 4 h, the planar views showed low background vascular activity in the lungs and cardiac region in addition to the sternal uptake, which showed two patterns: homogeneous in five patients and heterogeneous in 15. A long and narrow defect of uptake along the sternal midline was the most characteristic finding. At 4 h, in addition to the background vascular activity in the lungs and cardiac region, the greatest uptake on SPET was in the sternum anteriorly and the marrow spine posteriorly without any focal uptake, allowing visualization of the mediastinum free of focal activity. At 20 h, both the planar and SPET images showed a higher organ-to-background ratio. Knowledge of these post-surgical patterns will make it easier to interpret planar and SPET images when 99Tcm-HMPAO-labelled leukocytes are used in the diagnosis of mediastinitis and sternal infections in patients who had previously undergone median sternotomy. Planar views were better for the assessment of sternal uptake, but SPET views were better for the direct visualization of the mediastinum by eliminating overlapping sternal uptake.

Adult↗
PubMed1999

Relationship of lead in drinking water to bone lead levels twenty years later in Boston men: the Normative Aging Study.

Tap water in a city like Boston, which has old houses containing lead plumbing, is known to be a significant source of potential lead exposure. Bone lead levels integrate exposure over many years, and in vivo bone lead measurements have recently become possible with the advent of K x-ray fluorescence instruments. Thus we examined the relationship between first morning tap-water lead levels measured in homes in the 1970s and levels of lead in bone measured in the 1990s among middle-aged to elderly men who lived in those homes. We studied 129 participants in the Normative Aging Study who had lead measured in their homes' tap water in 1976 and 1977 by graphite furnace-atomic absorption spectrophotometry. From 1991 to 1995, the same subjects had blood lead levels measured by graphite furnace-atomic absorption spectroscopy and tibia and patella bone lead levels measured by K x-ray fluorescence. We ran multivariate linear regression models predicting bone lead levels that adjusted for factors which had previously been linked with this outcome in the Normative Aging Study (age, pack-years of smoking, and educational level). Among subjects who lived in houses with > or = 50 micrograms lead/liter of first morning tap water representing water that had been standing overnight in the plumbing in 1976 and 1977, those who reported medium or high levels of tap-water ingestion (> or = 1 glass/day) had progressively higher patella lead levels than did those with low levels of ingestion (< 1 glass/day). No such relationship was found among subjects who lived in houses with < 50 micrograms lead/liter of first morning tap water in 1976 and 1977. We conclude that ingestion of lead-contaminated tap water is an important predictor of elevated bone lead levels later in life.

Adult↗
PubMed1999

Structural and ultrastructural study of GH, PRL and SMT cells in male goat by immunocytochemical methods.

The structural and ultrastructural characteristics of adenohypophyseal growth hormone (GH)-, prolactin (PRL)- and GH-PRL (SMT)-secreting cells were studied using immunocytochemical techniques in two normal and one lactating male goat. SMT cells were found in both types of males, which showed the same characteristics as those reported for the female. PRL and SMT cells were more frequent in the lactating male, which reflects their greater galactopoietic activity. GH cells did not seem to influence this process significantly.

Animals↗
PubMed1999

Prospective study of the clinical course, prognostic factors, causes of death, and survival in patients with long-standing Zollinger-Ellison syndrome.

PURPOSE: The long-term clinical course of unselected patients with gastrinomas as well as other functional pancreatic endocrine tumors (PETs) in whom the excess-hormone state is controlled is largely unknown. To address this issue, patients with gastrinomas were assessed. PATIENTS AND METHODS: Two hundred twelve patients with Zollinger-Ellison syndrome (ZES) were prospectively studied. All had controlled acid hypersecretion and were assessed yearly, with a mean follow-up period of 13.8+/-0.6 years (range, 0.1 to 31 years). Annual assessments of possible factors that might affect prognosis or treatment approaches were performed, such as those for tumor size and location; the presence, location, and extent of metastases; and the occurrence of ectopic Cushing's syndrome or another PET syndrome. Deaths were categorized as ZES-related or non-ZES-related and classified into different causes. RESULTS: Thirty-one percent of patients died, all of non-acid-related causes. One half died of a ZES-related cause; they differed from those who died of non-ZES deaths by having a large primary tumor, more frequently a pancreatic tumor; lymph node, liver, or bone metastases; ectopic Cushing's syndrome; or higher gastrin levels. The extent of liver metastases correlated with survival rate. The presence of liver metastases alone only moderately decreased survival time; however, the additional development of bone metastases or ectopic Cushing's syndrome markedly decreased survival rate. CONCLUSIONS: In ZES, gastrinoma growth is now the main single determinant of long-term survival, with one half of patients dying a gastrinoma-related death and none an acid-related death. Large primary tumors that are pancreatic in location, the development of liver metastases, (especially if associated with bone metastases or Cushing's syndrome), and the extent of liver metastases are all important prognostic factors. The identification of these factors allows the recognition of subgroups that can be used to tailor antitumor treatment approaches.

Adolescent↗
PubMed1999

Noise assessment during aircraft run-up procedures.

BACKGROUND: A comprehensive noise survey was conducted at Oficinas Gerais de Material Aeronautico (OGMA), Alverca, Portugal, and at several Portuguese Air Force (PoAF) bases, as part of an ongoing occupational noise assessment program. The major objectives consisted of measuring and analyzing noise radiated by various types of military aircraft while undergoing maintenance, repair, or testing. METHODS: Amplitude, frequency, time history and statistical analysis were conducted on noise emitted by aircraft during run-up procedures. Analysis and evaluation used various noise indexes (Leq and Lmax), frequency spectra, and sound pressure time histories for the assessment of noise exposure on the employees during their working life span. RESULTS: The results show a predominance of large pressure amplitudes within the lower frequency bands. This was correlated with long-term clinical observations in these workers. This study corroborates the definition of vibroacoustic disease as a systemic, noise-induced occupational pathology caused by long-term (>10 yr) exposure to large pressure amplitude (> or = 90 dB SPL) and low frequency (< or = 500 Hz) noise.

Aerospace Medicine↗
PubMed1999

Specificity of somatostatin receptor scintigraphy: a prospective study and effects of false-positive localizations on management in patients with gastrinomas.

UNLABELLED: Somatostatin receptor scintigraphy (SRS) is being increasingly used both for localization and, in some cases, diagnosis of various diseases. There are no prospective studies of its specificity or occurrence of false-positive results and their effects on management. This study was designed to address both of these issues. METHODS: Over a 40-mo period, 146 consecutive patients with Zollinger-Ellison syndrome (ZES) undergoing 480 SRS examinations were studied prospectively. Patients were admitted at least yearly and underwent SRS as well as conventional imaging studies (ultrasonography, CT, MRI) and angiography, if necessary. All admissions were assigned to one of five different clinical categories in which imaging studies had different purposes. SRS localizations were classified as true-positive or false-positive based on preset criteria. A false-positive result was determined to change clinical management based on five preset criteria. RESULTS: Of all SRS examinations, 12% resulted in a false-positive localization for a neuroendocrine tumor or its metastases, resulting in a sensitivity of 71%, specificity of 86% and positive and negative predictive values of 85% and 52%, respectively. Extra-abdominal false-positive localizations (2/3) were more common than intra-abdominal (1/3). Thyroid disease, breast disease and granulomatosis lung disease were the most frequent causes of extra-abdominal false-positive localizations. Accessory spleens, localization to previous operative sites, renal parapelvic cysts and various procedural aspects were the most frequent causes of intra-abdominal false-positive localizations. Of all SRS studies, 2.7% resulted in a false-positive result that altered management. CONCLUSION: False-positive SRS localization occurs in 1 of 10 patients with ZES. By having a thorough understanding of diseases or circumstances that result in false-positive localization and comparing the SRS result with the clinical context, the percentage of patients in whom false-positive localization results in altered management can be reduced to below 3% and the correct diagnosis made in almost every case.

False Positive Reactions↗
PubMed1999

[Abdominal scintigraphy with 99MTc-HMPAO-labelled leukocytes. Utility of the quantification in the evaluation of the inflammatory activity of Crohn's disease and ulcerative colitis].

We aimed to determine the activity of Crohn's Disease (CD) and Ulcerative Colitis (UC) with this radiotracer and to compare it with the normal clinical indexes. 32 patients with CD (19 women) and 18 with UC (13 women) were studied and a sequential abdominal 99mTc-HMPAO-label leukocyte scintigraphy was performed after evaluating the activity clinical scales indexes (Harvey's for CD and Lictiger for UC). Quantification was performed to obtain intestinal activity indexes in regards to intestinal uptake with background, bone marrow, liver and spleen, comparing them with the clinical indexes. In CD, all scintigraphic indexes showed a significant correlation (p < 0.001) with clinical activity. The best results were obtained with gut/background (r: 0.73) and gut/bone marrow (r: 0.72). In UC, we obtain a lower correlation between clinical and scintigraphic indexes. Significant correlations (p < 0.05) were only found with the gut/background (r: 0.52) and gut/bone marrow growth indexes (r: 0.58). The others showed no correlation. In conclusion, IBD activity estimated with 99mTc-WBC and scintigraphy indexes showed moderate correlation with clinical scales. However, the information of the scintigraphy was very useful in the management of these patients.

Adult↗
PubMed1998

Expression of neuronal nitric oxide synthase during embryonic development of the rat cerebral cortex.

The expression of neuronal nitric oxide synthase (nNOS) during the development of the rat cerebral cortex from embryonic day (E) 13 to postnatal day (P) 0 was analyzed by immunocytochemical procedures using a specific antibody against rat brain nNOS. Expression of nNOS was first seen on E14 in cells of Cajal-Retzius morphology located in the marginal zone. Neuronal NOS immunoreactivity persisted in this layer throughout the embryonic period and only began to decrease on E20, when neuronal migration is coming to an end. From E17 onwards, migrating neurons expressing nNOS were observed in the intermediate zone with their leading processes directed towards the cortical plate. At the same time, efferent nNOS-immunoreactive axons originating from cortical plate cells entered the intermediate zone. From E19 onwards, cells expressing nNOS and with the morphological characteristics of migrating cells were observed in and near the subventricular zone. Confocal analysis of double immunostaining for nNOS and glial fibrillary acidic protein or nestin showed no coexpression of nNOS and glial markers in these cells, suggesting that nNOS-positive cells leaving the subventricular zone were not glial cells. Commissural, callosal and fimbrial fibers were seen to express nNOS on E18 and E19. This expression decreased from E20 and was very weak on E21 and P0. The observations suggest that nitric oxide is synthesized during embryonic life in relation to maturational processes such as the organization of cerebral lamination, and is involved in controlling migrational processes and fiber ingrowth.

Animals↗
PubMed1998

[Clinical factors that affect the detection of BCR-ABL transcripts after allogenic bone marrow transplantation for chronic myeloid leukemia].

BACKGROUND: To evaluate the relationship between clinical parameters and the ability to detect BCR-ABL-positive cells in a series of 27 long survivor patients after allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukemia (CML). PATIENTS AND METHODS: A total of 78 samples obtained between 1 and 160 months after BMT were analyzed for the presence of the BCR-ABL transcript detected by the reverse-transcription polymerase chain reaction (PCR) using nested primers. Median follow up was 83 months. RESULTS: 16 patients were persistently PCR-positive and 7 patients persistently PCR-negative. The original transcript became negative in four patients. Only two of the positive cases developed hematologic relapse during the period of study. High white blood cell counts before BMT (17.88 vs 10.12 x 10(9)/l; p = 0.008) and immunosuppressive therapy for chronic graft-versus-host disease (p < 0.05) were associated with an increased ability to detect residual BCR-ABL positive cells. CONCLUSIONS: Our data show that most patient are persistently BCR-ABL positive after BMT for CML. If these findings represents a dynamic balance between the tumour burden prior BMT and the immunological capability of the graft must be confirmed in further studies.

Adolescent↗
PubMed1998

Neuronal and inducible nitric oxide synthase and nitrotyrosine immunoreactivities in the cerebral cortex of the aging rat.

Neuronal and inducible nitric oxide synthase (nNOS and iNOS) and nitrotyrosine immunoreactivities were localized and semiquantitatively assessed in the cerebral cortex of aged rats by means of light microscopic immunocytochemistry and Western blotting, using a new series of specific polyclonal antibodies. In the aged rats the strongly nNOS-immunoreactive multipolar neurons found in layers II-VI of the cortex of young rats were seen in similar numbers, but showed varicose, vacuolated, and fragmented processes, with an irregular outline and loss of spines. A large number of more weakly nNOS-positive neurons, characterized by a ring of immunoreactive cytoplasm, and not seen in young rats, were observed in layers II-VI of aged rat cortex. While no iNOS-immunopositive neurons were found in the cortex of young rats, a large number of such neurons appeared throughout the aged rat cortex. Nitrotyrosine-positive cells outnumbered total NOS-positive neurons in the cortex of young rats, but this relation was inverted in the aged rats, although these showed a slight increase in the number and staining intensity of nitrotyrosine-positive cells. Western blots of brain extracts showed a several-fold increase in both nNOS- and iNOS-immunoreactive bands in the aged rat, but a less marked increase in nitrotyrosine-containing proteins. The results suggest that while nNOS and iNOS expression is substantially increased in the aged rat cortex, this is not necessarily accompanied by a proportionate increase in nitric oxide synthesis. The mechanisms underlying the increased expression of nNOS and iNOS, and the functional implications of this increase, require elucidation.

Aging↗
PubMed1998

Distribution of nitric oxide synthase in the esophagus of the cat and monkey.

The distribution of nitrergic neurons and processes in the esophagus of the cat and monkey was studied by light microscopic immunocytochemistry using a specific antibody against purified rat brain nitric oxide synthase and immunoperoxidase procedures. Immunoreactive nerve fibers were found pervading the myenteric plexus, submucous plexus and plexus of the muscularis mucosae, and particularly in the lower esophagus a few immunoreactive fibers entered the epithelium as free nerve endings, some of which derived from perivascular fibers. In the upper esophagus immunoreactive motor end-plates were found in the striated muscle. Thirty-forty-five percent of neuronal cell bodies found in the intramural ganglia and along the course of nerve fiber bundles were immunoreactive and were of the three morphological types earlier described. In the intramural ganglia immunoreactive nerve fibers formed a plexus in which varicose nerve terminals were in close relation to immunoreactive and non-immunoreactive neurons. The intramural blood vessels that crossed the different layers of the esophageal wall were surrounded by paravascular and perivascular plexuses containing immunoreactive nerve fibers. The anatomical findings suggest that nitric oxide is involved in neural communication and in the control of peristalsis and vascular tone in the esophagus. In the lower esophagus a few nitrergic nerve fibers are anatomically disposed to subserve a sensory-motor function.

Animals↗
PubMed1998

Penetrating atherosclerotic aortic ulcer: documentation by transesophageal echocardiography.

OBJECTIVES: This study sought to describe the ability of transesophageal echocardiography (TEE) to document the presence of penetrating atherosclerotic aortic ulcers and their complications. BACKGROUND: TEE has greatly enhanced our ability to assess patients with suspected aortic disease. However, the utility of this technique in the diagnosis of penetrating atherosclerotic aortic ulcers is still undefined. METHODS: TEE was performed prospectively in 194 patients to evaluate aortic disease. Twelve patients with the diagnosis of aortic ulcers or their complications were specifically studied. The diagnosis was confirmed by pathologic studies in six patients and by an additional diagnostic technique (angiography, computed tomography or magnetic resonance imaging) in the other six. All 12 patients were hypertensive and presented with chest or back pain; the mean age was 65 years (range 56 to 79). The initial working diagnosis was acute aortic dissection in nine patients. Aortic ulcers were located in the descending thoracic aorta in eight patients, the aortic arch in two and the ascending aorta in two. RESULTS: TEE could detect aortic ulcers or their complications in 10 patients but failed to detect these lesions in the remaining 2 (1 with aortic ulcers in the distal ascending aorta and 1 with aortic ulcers in the aortic arch). In four patients, aortic ulcers were detected as a calcified focal outpouching of the aortic wall and were associated with concomitant aneurysmal dilation of the aorta in two patients and with a small localized intramural hematoma in one. TEE visualized a partially thrombosed pseudoaneurysm complicating an aortic ulcer in the descending thoracic aorta of two patients. Four patients had an aortic ulcer complicated by a "limited aortic dissection" in the descending aorta that could be detected by TEE. Five patients underwent operation, two because of aneurysmal dilation of the aorta and three because of aortic dissection; two patients died of aortic rupture; the remaining five did well (11-month follow-up) without operation. CONCLUSIONS: Aortic ulcers should be included in the differential diagnosis of chest or back pain, especially in elderly hypertensive patients. These ulcers and their complications may be recognized by TEE.

Aged↗
PubMed1998

Distribution of catecholaminergic afferent fibres in the rat globus pallidus and their relations with cholinergic neurons.

The topographical distribution of catecholaminergic nerve fibres and their anatomical relationship to cholinergic elements in the rat globus pallidus were studied. Peroxidase-antiperoxidase and two-colour immunoperoxidase staining procedures were used to demonstrate tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), phenylethanolamine N-methyltransferase (PNMT) and choline acetyltransferase (ChAT) immunoreactivities, combined with acetylcholinesterase (AChE) pharmacohistochemistry. TH immunoreactive nerve fibres were seen to enter the globus pallidus from the medial forebrain bundle. The greatest density of such fibres was found in the ventral region of the globus pallidus, which was also characterized by the greatest density of ChAT immunoreactive neurons. TH immunoreactive nerve fibres showed varicose arborizations and sparse boutons, which were occasionally seen in close opposition to cholinergic structures. In all regions of the globus pallidus, there were also larger, smooth TH immunoreactive nerve fibres of passage to the caudate putamen. A smaller number of DBH immunoreactive nerve fibres and terminal arborizations were found in the substantia innominata, internal capsule and in the globus pallidus bordering these structures. A few PNMT immunoreactive nerve fibres in the substantia innominata and internal capsule did not enter the globus pallidus. Electron microscopy revealed TH immunoreactive synaptic profiles in the ventromedial area of the globus pallidus corresponding to the nucleus basalis magnocellularis of Meynert (nBM). These made mainly symmetrical and only a few asymmetrical synaptic contacts with dendrites containing AChE reaction product. The results indicate that cholinergic structures in the nBM are innervated by dopaminergic fibres and terminals, with only a very small input from noradrenergic fibres.

Acetylcholinesterase↗
PubMed1998

Autologous peripheral blood stem cell transplantation (PBSCT) mobilized with G-CSF in AML in first complete remission. Role of intensification therapy in outcome.

In order to determine if peripheral blood stem cells (PBSC) collected after priming with G-CSF in AML in first complete remission (CR) can be used for autologous transplantation and to evaluate the efficacy of early intensification therapy as in vivo purging, we studied 35 consecutive patients with AML in first CR. After standard induction and consolidation chemotherapy, 24 of them were treated with one (10 patients) or two (14 patients) cycles of high-dose cytarabine plus etoposide prior to PBSC collection. G-CSF was used as the priming agent. Of the 35 patients scheduled for peripheral blood stem cell transplantation (PBSCT), three relapsed before transplantation, and the 32 remaining underwent PBSCT. High-dose therapy consisted of either total body irradiation plus cyclophosphamide or busulphan plus cyclophosphamide. The median number of CD34+ cells infused was 3.24 x 10(6)/kg (range 0.15-14). The median times to reach a PMN count of 0.5 x 10(9)/l and a platelet count of 50 x 10(9)/l were 12 (8-28) and 30 (11-345) days, respectively. There was no transplant-related mortality. Twelve patients relapsed between 2 and 21 months post-PBSCT. With a median follow-up of 28 months, actuarial disease-free survival (DFS) is 52.41 +/- 9% in the intent-to-treat group and 57.4 +/- 9.8% in patients who underwent PBSCT. The probability of DFS is significantly higher for patients who receive early intensification therapy prior to both PBSC collection and PBSCT as compared with patients that do not: 68.8 +/- 10.27% vs 35.5 +/- 12.6%, P = 0.0418. These results indicate the feasibility of PBSCT in AML using G-CSF-mobilized PBSC. The use of intensification treatment as 'purging in vivo' prior both to collection of PBSC and PBSCT significantly reduces the risk of relapse in this group of patients.

Adolescent↗