Search PubMed⌕ Search

Biomedical subjects

F Gomez

Publications and source records attributed to F Gomez.

At least 91 records · Page 5Linked to original sources

[Test with ovine corticotropin-releasing hormone (oCRH): clinical application and reference values in the young adult and the postmenopausal women].

CRH (corticotropin-releasing hormone) is a hypothalamic polypeptide that stimulates ACTH secretion by the anterior pituitary and, subsequently, cortisol secretion by the adrenal cortex. CRH test administration is indicated in the differential diagnosis of Cushing syndrome and in the assessment of corticotropic function in different pituitary conditions. Both human CRH (hCRH) and ovine CRH (oCRH) can be used by i.v. injection. Intrinsic ACTH-releasing activities of the two molecular forms are similar. Nevertheless, and contrary to hCRH, oCRH does not interact with the human CRH specific binding protein (CRH-BP) and the use of this ovine form could be useful in testing pituitary function while avoiding possible changes in peptide activity due to protein binding. The present study was conducted in 3 distinct groups of human volunteers to evaluated the ACTH and cortisol responses to i.v. oCRH (1 micrograms per kg body weight) at noon (oCRH test). 24 healthy, nonobese subjects, not under medication, participated in the study. The first group consisted of 8 young men, the second of 8 women of childbearing age and the third of 8 menopausal women. Tolerance to the oCRH test was excellent in all 3 groups. A significant increase in plasma ACTH and cortisol was observed in all the subjects, with peak occurrence for ACTH between 15 and 60 minutes after oCRH and between 20 and 120 minutes for cortisol. The responses were not sex-related among the young subjects, but the menopausal women displayed a higher cortisol increase than the other 2 groups.

Adrenocorticotropic Hormone↗

Role of iron in T cell activation: TH1 clones differ from TH2 clones in their sensitivity to inhibition of DNA synthesis caused by IgG Mabs against the transferrin receptor and the iron chelator deferoxamine.

TH1 and TH2 helper T cell clones have been studied with respect to their sensitivity to inhibition of DNA synthesis by an IgG anti-transferrin receptor antibody (ATRA), the iron chelator deferoxamine, and the combination of the two reagents. TH1 clones are very sensitive to ATRA-mediated inhibition of DNA synthesis while TH2 clones are very resistant, but both TH1 and TH2 clones show significant down-modulation of surface transferrin receptors after ATRA exposure. TH2 clones exhibit larger chelatable iron storage pools than TH1 clones, however, and even partial chelation of TH2 cell storage iron does not fully convert a TH2 clone to the ATRA sensitivity pattern of a TH1 clone. It is therefore proposed that the greater resistance of TH2 clones to ATRA mediated inhibition derives from the combined effects of larger and less labile iron storage pools. These studies provide novel evidence indicating that nonuniform iron metabolism can exist within the T cell compartment and thus raise questions as to why such differences exist and how they can be integrated into models of the T cell activation process. These studies also suggest that the cell-mediated immune response in vivo, which is known to be sensitive to iron deficiency, may be evoked by effector cells which resemble TH1 clones insofar as iron metabolism is concerned.

Animals↗

Dissociated recovery of cortisol and dehydroepiandrosterone sulphate after treatment for Cushing's syndrome.

We have studied the variation of ACTH, cortisol and DHEA-S plasma levels in 6 patients before and up to 15 months after surgical remission of Cushing's syndrome in order to compare the relative dependency of cortisol and adrenal androgens towards ACTH. Three patients with adrenal adenoma were treated by unilateral adrenalectomy. Three other patients with Cushing's disease underwent transsphenoidal pituitary tumorectomy. Preoperative ACTH was undetectable in patients with adrenal adenoma and high-normal or elevated in patients with Cushing's disease. All patients became rapidly hypocortisolemic after surgery and ACTH and cortisol levels eventually recovered at different intervals. Patients with adrenal adenoma had an initially low DHEA-S which failed to normalize for the entire follow-up period. Patients with Cushing's disease had normal or high-normal DHEA-S which became low immediately after surgery, following ACTH decrease, and it remained low during the entire follow-up period. In conclusion, after removal of corticotropic inhibition secondary to excess cortisol, DHEA-S remains suppressed for a longer period of time than cortisol. Moreover it only takes a short period of relatively low ACTH (after pituitary tumor excision) to induce a long lasting DHEA-S inhibition. Therefore the DHEA-S secreting adrenal cells seem to be more sensitive to the lack of corticotropic stimulation than cortisol secreting cells.

Adrenal Gland Neoplasms↗

CV 205-502 treatment of macroprolactinomas.

CV 205-502, a benzoquinoline, is a new nonergot dopamine agonist compound which has been shown to be effective in lowering PRL levels in normal volunteers and in hyperprolactinemic women. Seven patients (4 men and 3 women) presenting with hyperprolactinemia due to macroprolactinoma were treated with CV 205-502 given as a single daily dose at bedtime for up to 12 months. Six patients presented with impaired gonadal function and 2 with galactorrhea. All patients but one had previously been treated with bromocriptine and 4 had undergone pituitary surgery (3 with complementary radiotherapy). Six patients responded within a few weeks to CV 205-502 treatment, PRL levels being normalized (4 patients, 0.075 to 0.150 mg/day) or significantly reduced to restore normal gonadal function (2 patients, 0.225 mg/day). The seventh patient, who had previously been resistant to bromocriptine, also failed to respond to CV 205-502 treatment even after high doses (0.450 mg/day). Under CV 205-502 treatment, follow-up with magnetic resonance imaging revealed a reduction in tumor size of up to 52% of the initial volume in the "PRL-responders" whereas an increase in tumor size was observed in the "nonresponding" patient. No biological disturbance appeared during CV 205-502 treatment and the drug tolerance was very good, with mild side-effects being reported by only 2 patients. In conclusion, CV 205-502, given once daily, appears to be a safe and effective alternative to other dopamine agonists in the treatment of macroprolactinoma, by reducing hyperprolactinemia and tumor size. It was, however, of no benefit in the one patient whose macroprolactinoma had been resistant to bromocriptine.

Adult↗

Influence of water conductivity on the efficiency and the reproducibility of electrohydraulic shock wave generation.

In an electrohydraulic generator, two underwater metal electrodes are connected with a capacitor charged to a high voltage. When the circuit is switched on, a plasma is generated reaching temperatures of thousands of K, resulting in a compressive pressure pulse. The formation of the plasma is a nonreproducible phenomenon inducing great variations of the pressure pulse. When the electrodes are immersed in an electrolyte instead of degassed water, the conditions of electrical discharge are dramatically modified. The latency time and the amplitude of the oscillations of the discharge current decrease as the conductivity of the electrolyte increases. For a conductivity of 7 omega.cm, there is no latency, and the critically damped discharge is achieved. The expanding pressure wave is increased by 10%, and the mean peak pressure value over 120 shocks at the second focus after focalization is increased by 50%. The relative standard deviation of the pressure value at the second focus is only 5%, while it is about 30% in ordinary water. The fragmentation efficiency is considerably increased because total fragmentation is obtained in 220 shocks instead of 450 shocks in ordinary water when standard stones are used, and in 131 shocks instead of 304 shocks when gallstones are used. Last, we show that the wear of the electrodes is reduced by a factor 8 when electrolyte is used. The improvement is supposed to have two causes: First, the energy is delivered into the medium in a shorter time, and, second, the center of the shock wave is always located at the same place. The decreased wear should make it possible to treat a much greater number of patients without changing electrodes, and the enhancement of the pressure should increase the efficiency of the fragmentation of the gallstones without aggravating the patient's pain.

Efficiency↗

In vivo glucocorticoid modulation of guinea pig splenic macrophage Fc gamma receptors.

Although glucocorticoids are widely used in the treatment of immunohematologic disease, their relative efficacy is uncertain. We used an animal model, which has helped to elucidate the role of splenic macrophage Fc gamma receptors in the clearance of IgG-coated cells, to investigate whether each Fc gamma receptor is modulated by glucocorticoids to the same extent and to examine the relative potency of three commonly used glucocorticoids. Cortisol, prednisone, and dexamethasone all impaired the clearance of IgG-coated erythrocytes. However, dexamethasone was more effective than either prednisone or cortisol (P less than 0.001). Furthermore, splenic macrophages isolated from glucocorticoid-treated animals expressed impaired Fc gamma receptor function. This effect was greater in macrophages isolated from dexamethasone-treated animals, as compared to either cortisol- or prednisone-treated animals (P less than 0.001). To assess the effect of glucocorticoids on the two types of guinea pig splenic macrophage Fc gamma receptors, Fc gamma R1,2 and Fc gamma R2, specific immunoglobulin isotypes were used to measure macrophage binding of IgG-sensitized erythrocytes. Cortisol and prednisone primarily affected Fc gamma R2, whereas dexamethasone inhibited the function of both guinea pig Fc gamma receptors. Furthermore, dexamethasone was more effective (P less than 0.01) than either prednisone or cortisol in inhibiting the ability of both receptors to bind IgG-sensitized cells. Fluorescence-activated cell sorter analysis and fluorescence microscopy with monoclonal antibodies specific for each of these two receptors demonstrated that essentially all splenic macrophages expressed both receptors, and that these glucocorticoids decreased the level of each Fc gamma receptor protein expressed, rather than altering receptor mobility and clustering in the macrophage membrane. The effect on both Fc gamma receptors was greatest with dexamethasone and least with cortisol. These studies demonstrate the significant role of guinea pig splenic macrophage Fc gamma R2 in immune clearance and in the binding of IgG-coated cells. They demonstrate a differential effect of glucocorticoid hormones on Fc gamma receptor function and on surface receptor protein. Furthermore, they suggest that dexamethasone may be a more effective glucocorticoid than either prednisone or cortisol in inhibiting the clearance of IgG-coated cells by its effect on splenic macrophage Fc gamma receptors.

Animals↗

Synergistic inhibition of lymphoid tumor growth in vitro by combined treatment with the iron chelator deferoxamine and an immunoglobulin G monoclonal antibody against the transferrin receptor.

Data are presented indicating that the growth of 5 out of 5 murine lymphoid tumors can be inhibited in a synergistic fashion in vitro by combined treatment with the iron chelator deferoxamine (DFO) and an immunoglobulin G (IgG) monoclonal anti-transferrin receptor antibody (ATRA). A two-way dose/response analysis shows that the ATRA becomes more efficient as an inhibitor with increasing doses of DFO. Flow cytometric studies further support the view that IgG ATRAS impair transferrin receptor (TR) function by causing TR down-modulation and degradation, even when the presence of DFO acts to promote increased cell surface TR expression. It is also shown that an IgG ATRA is nearly as effective as an IgM ATRA in inhibiting tumor cell growth when used in combination with DFO. Finally, studies with the iron chelator picolinic acid show that it produces only additive, or very slightly supra-additive, effects when used in combination with the ATRA. Therefore, these studies not only continue to suggest that combination chelator/ATRA therapy warrants further investigation as a tool in the therapy of hematopoietic malignancies, but also make the following new points: (1) the clinically familiar iron chelator deferoxamine, but not all iron chelators, produces synergistic inhibition of tumor growth in vitro with ATRAS; and (2) IgG ATRAS, which may be clinically more attractive reagents than IgA or IgM ATRAS because of better access to extra vascular tissue spaces, have unexpectedly been found to function as powerful growth inhibitors when used in combination with DFO.

Animals↗

Impaired function of macrophage Fc gamma receptors in end-stage renal disease.

Infection is a frequent complication in patients undergoing hemodialysis for end-stage renal disease and is the primary cause of mortality among such patients. Macrophages are important in host defense against infection largely because their Fc gamma receptors recognize antibody-coated bacteria. We therefore studied macrophage Fc gamma-receptor function in vivo and in vitro in 56 patients with end-stage renal disease who were on hemodialysis and in 20 healthy volunteers. The clearance of IgG-coated (sensitized) autologous red cells was decreased in 53 patients. The inhibition of clearance in the 56 patients was 52 +/- 3 percent at 1 hour, 41 +/- 5 percent at 1 1/2 hours, and 29 +/- 5 percent at 2 hours (P less than 0.001). The clearance of unsensitized erythrocytes and heat-altered autologous erythrocytes was normal. The impairment of clearance was not correlated with age, sex, nutritional status, HLA haplotype, or the presence of circulating immune complexes. The recognition of these IgG-sensitized red cells in vitro by Fc gamma RI (an Fc gamma-receptor protein that binds monomeric IgG) on blood monocytes from the patients was also significantly decreased (P less than 0.001) but was partially improved by hemodialysis. Nine patients had severe infections during a two-year follow-up period. The clearance of IgG-coated cells in these patients (half-time, 12.9 +/- 1.7 hours) was significantly impaired, as compared with that in the 47 patients without severe infections (half-time, 4.4 +/- 1.8 hours; P less than 0.001). We conclude that macrophage Fc gamma-receptor function is impaired in patients with end-stage renal disease who are undergoing hemodialysis, and that this impairment probably contributes to the observed immunodepression and high prevalence of infection among such patients.

Adult↗

Endoscopic sphincterotomy in hepatic hydatid disease open to the biliary tree.

Communication with the biliary tree is the most common complication of hydatid disease of the liver and up to a few years ago surgery was the only way to treat it successfully. The introduction of endoscopic sphincterotomy represented a great advance in the management of this disease. We report the results obtained with this technique in ten patients after surgical treatment of hepatic hydatid disease open to the biliary tree. The results were satisfactory in all cases, with no morbidity or mortality. Endoscopic sphincterotomy is now the first choice treatment for surgical complications of hepatic hydatid disease open to the biliary tree, as well as the drainage procedure of choice in patients with cholangitis due to hydatid disease.

Adolescent↗

Huntington's disease in Venezuela: 7 years of follow-up on symptomatic and asymptomatic individuals.

Persons symptomatic and at risk for Huntington's disease (HD) from a large extended family in the state of Zulia, Venezuela, have been followed prospectively for 7 years. Between 1981 and 1988, 593 people were examined, of whom 128 had symptomatic HD and 171 persons at risk had examination abnormalities that were insufficient to meet criteria for diagnosis. The remaining 294 had normal examinations. Abnormalities of saccadic eye movement and slowness of rapid alternating movements were the most common abnormalities found in at-risk individuals. Thirty persons who did not meet criteria for diagnosis at their first examination have subsequently been diagnosed with symptomatic HD. Their average age at diagnosis was 33.5 +/- 8.3 (SD) years. The likelihood of developing symptomatic HD within 3 years was 3% for those persons with normal first examinations, 23% for those with mildly abnormal first examinations, and 60% for those with highly abnormal first examinations. The rate of disease progression in early symptomatic cases were 1.4 +/- 0.1 (SEM) points per year on the Shoulson-Fahn functional capacity scale. Paternal or maternal inheritance did not appear to affect the rate of progression in this group of individuals. The data suggest that there is not a discrete age of onset but rather a prolonged period of time during which symptoms unfold.

Adolescent↗

Subfemtomole enzyme immunoassay for human growth hormone using affinity chromatography and enzyme amplified detection.

An immunometric assay is described which allows fast detection of attomole amounts of an antigen. The sensitivity is 100 to 1000 times better than that of classical sandwich immunometric assays. Our system allowed the measurement of human growth hormone in the range of 0.1 amol to 100 fmol in a 4-h time period overall. A chromatography column is sequentially filled with two immunoaffinity resins: SP-M1--E1-Ab1 in the upper half and SP-M2--E2-Ab2 in the lower half, where Ab1 and Ab2 represent complementary antibodies reacting with the antigen to be assayed, E1 and E2 represent enzymes, M1 and M2 represent substances reacting reversibly with E1 and E2, respectively, and SP represents the chromatographic solid phase; the sign - represents covalent linkages and the sign--reversible linkages. The sample solution is passed through the column, resulting in binding of the antigen to the first encountered antibody, yielding the immobilized complex SP-M1--E1-Ab1--Ag. The M1 bound is then destabilized by washing with solution of agonist to M1. The freed complex is immediately trapped by the second antibody in the lower part of the column, resulting in the entity SP-M2--E2-Ab2--Ag--Ab1-E1. After a washing step, and amplified detection allows the measurement of the antigen through the activity of the enzyme E1. The antigen-antibody reactions occur in the presence of a very large excess of antibody. The continuous equilibrium displacement due to the chromatographic procedure enhances the yield of complex formation. These factors explain the extremely low levels (subattomole) capable of being detected with this original technique.

Animals↗

Psychoneuroendocrinological and immunological parameters in cancer patients: involvement of stress and depression.

Plasma noradrenaline (NA), adrenaline (A), dopamine (DA), platelet serotonin (pS), free serotonin (fS), cortisol (CRT), growth hormone (GH), peripheral blood lymphocytes (lymph), lymphocyte subpopulations (LSS) and CD4/CD8 ratio were serially assessed in 50 non-medicated, advanced cancer patients (spontaneous evolution) and in age- and sex-paired controls. Clonidine tests and psychiatric evaluations were also serially performed. Patients showing long symptomless periods had all normal values except for raised pS, whereas those who remained free of symptoms for only a short time had raised NA, A and CRT, plus lowered pS values. Further increases in NA, A and CRT, plus additional increases in DA and fS, occurred during exacerbation periods, during which times reductions in lymph, LSS and NK also were observed. Patients in terminal stages showed maximal decreases of all neurotransmitters and immunological parameters; only DA and fS remained raised. Psychiatric interviews performed simultaneously with the clonidine tests revealed a low incidence of moderate depression during symptomless periods and no depression during exacerbation periods. Several significant positive and negative correlations between neurotransmitters and immunological parameters were found during exacerbation periods. Pain, although not intense, and other symptoms required occasional administration of low doses of non-opiate analgesics.

Adult↗

[Reconstruction of the proximal insertion of the anterior cruciate ligament. Studies on the accuracy of a non-instrumental method].

The isometry of the femoral and tibial insertion is of decisive importance for the stability of a prosthetic anterior cruciate ligament. A large number of techniques and instruments have been developed to determine the point of isometric femoral insertion. Experiments with 20 cadaveric knees show that the proximal insertion of the anterior cruciate ligament is accurately reconstructed by means of the surgical procedure briefly presented in this paper; the use of positioners is not necessary.

Anterior Cruciate Ligament↗

Purification and characterization of five variants of phospholipase A2 and complete primary structure of the main phospholipase A2 variant in Heloderma suspectum (Gila monster) venom.

1. Five increasingly anionic variants (Pa1-Pa5) of Ca2+-dependent phospholipase A2 were purified to homogeneity from the venom of the lizard Heloderma suspectum (Gila monster). The purification procedure was based on semi-preparative reverse-phase HPLC followed by anion-exchange HPLC and analytical reverse-phase HPLC. 2. Their Mr were 17,000-18,000, as deduced by SDS/PAGE. Specific activities tested by the capacity to hydrolyze phosphatidylcholines at pH 8.5 decreased as follows: Pa3 greater than Pa5 greater than Pa4 greater than Pa1 greater than Pa2. These activities showed the same optimum pH (9.0), were mainly of the phospholipase A2 type and were lost upon p-bromophenacyl bromide treatment. 3. All five phospholipases efficiently stimulated amylase release from dispersed rat pancreatic acini at pH 7.4, their potency decreasing as follows: Pa2 greater than Pa1 approximately equal to Pa4 greater than Pa3 approximately equal to Pa5. No deleterious effect was apparent based on the lack of lactate dehydrogenase release. 4. The five variants, Pa1-Pa5, differed significantly in amino acid composition and this, together with distinct antigenic properties of Pa2 and Pa5, establishes the subheterogeneity of this new type of phospholipase A2, despite the fact that the N-terminal amino acid sequence (31 residues) of Pa1-Pa5 was exactly the same. 5. The full sequence of the major variant, Pa5, showed that this 142-amino-acid protein exhibited greater similarity to the bee venom enzyme than to any class I or class II secretory phospholipase A2 from snake venom and mammalian pancreas. While Pa5 displayed the highly conserved region between Asp30 and Cys39 (the essential active site of all phospholipases A2), its salient original points included 10 half-cystine residues only, an incomplete N-terminal sequence, large changes in the putative calcium loop, several alterations after the active site and a C-terminal extension never seen in other phospholipases A2, with the only exception being bee venom.

Amino Acid Sequence↗

Monocyte Fc gamma receptor recognition of cell-bound and aggregated IgG.

Monocyte and macrophage Fc gamma receptors are important components in the recognition of IgG-coated cells and IgG-containing immune complexes. Two proteins have been identified on human peripheral blood monocytes that can function as Fc gamma receptors, Fc gamma RI (70 Kd) and Fc gamma RII (40 Kd). We studied the role of Fc gamma RI and Fc gamma RII on human monocytes by examining their binding of IgG-sensitized cells (human IgG anti-D-coated RBCs and rabbit IgG-sensitized sheep RBCs) and their binding of human trimeric IgG. To examine the function of monocyte Fc gamma RII, we used an anti-Fc gamma RII monoclonal antibody (MoAb) that competes for the Fc gamma RII ligand binding site. Preincubation of monocytes with saturating concentrations of anti-Fc gamma RII MoAb did not alter the recognition of IgG (anti-D)-sensitized human RBCs by monocytes. Furthermore, ligand-binding studies demonstrated that anti-Fc gamma RII antibody altered neither the number nor the affinity of monocyte-binding sites for human IgG trimer. Anti-Fc gamma RII inhibited monocyte binding of rabbit IgG-sensitized sheep RBCs, but only at low ionic strength or temperature when increased numbers of monocyte Fc gamma RII were expressed. At low ionic strength and 4 degrees C, anti-Fc gamma RII also partially inhibited monocyte binding of human trimeric IgG. Thus, monocyte Fc gamma RII does not appear to recognize IgG-sensitized RBCs or trimeric IgG at physiologic temperatures and ionic strength. The data suggest that Fc gamma RI is the primary Fc gamma receptor on monocytes involved in the binding of IgG (anti-D)-sensitized erythrocytes and low mol wt complexes of IgG.

Animals↗

[The dual protective effect of fish oil in preventing coronary diseases].

We studied the effect of incorporation of eicosapentaenoic and docosahexaenoic acid into the normal Western diet in nine human volunteers for 6 weeks. They received 1.5 g per day of omega 3-polyunsaturated fatty acids (W3-PUFA) for 3 weeks followed by 3 weeks with supplementation of 3.0 g per day. A control period of 3 weeks preceded PUFA supplementation. A significant effect on lipids was found in the total triglycerides and VLDL-triglyceride fractions (p less than 0.025). The ratio VLDL-triglyceride over HDL-cholesterol was also significantly diminished after 6 weeks of treatment (0.86 +/- 0.15 vs 1.01 +/- 0.19, p less than 0.02). Prolongation of the bleeding time was clearly demonstrated after 6 weeks of supplementation (10.6 +/- 1.3 min vs 6.2 +/- 0.6 min). Platelet aggregation stimulated by either ADP or collagen was significantly diminished after W3-PUFA supplementation (p less than 0.025 and p less than 0.005 after ADP and collagen respectively). The lag time of platelet aggregation was significantly prolonged (94 +/- 12 vs 56 +/- 2 sec, p less than 0.005) and the maximum speed reaction of the primary phase of the reaction was significantly diminished (1.3 +/- 0.2 vs 1.6 +/- 0.2 mm/sec, p less than 0.02). In conclusion, in the light of this study W3-PUFA supplementation leads to two different benefits in cardiovascular prevention. First, a significant diminution of total plasma triglyceride has been shown and, second, prolongation of the bleeding time and diminution of the platelet aggregation have been demonstrated.

Adult↗

Pancreatic insuloma causing Cushing's syndrome.

The advent of new diagnostic procedures such as petrosal venous sampling and CRF testing has improved the possibilities of precise location of the site of hormonal overproduction in Cushing's syndrome. We report on a case of ectopic ACTH-dependent Cushing's syndrome in which the use of such techniques helped to locate the tumor. A 45-year-old woman with definite ACTH-dependent Cushing's syndrome was referred to our clinic for evaluation. ACTH, cortisol and urinary 17OHCS failed to suppress on high dose dexamethasone oral administration. Computerized tomography showed bilateral adrenal hyperplasia and an empty sella turcica. ACTH and cortisol did not increase after CRF administration. Staged caval system catheterism via both femoral veins up to the inferior petrosal sinuses, including after CRF administration, demonstrated no ACTH gradient between staged samples and simultaneous peripheral venous blood. This suggested a tumor drained by the portal system. An abdominal ultrasonography demonstrated a pancreatic mass, that was surgically excised and appeared as a benign islet cell tumor. Portal vein ACTH promptly decreased after tumor excision and postoperative peripheral cortisol and ACTH were normal. On immunostaining the tumor cells proved to be positive for ACTH.

ACTH Syndrome, Ectopic↗