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Biomedical subjects

F Gomez

Publications and source records attributed to F Gomez.

At least 37 records · Page 2Linked to original sources

[Primary bilateral adrenal lymphoma].

When abdominal imaging reveals the existence of unsuspected adrenal masses, a diagnostic strategy is necessary. We report the case of a woman presenting with pulmonary embolism, in whom abdominal ultrasound revealed voluminous masses in both adrenals without clinical or biological signs of hormone hypersecretion, but with mild primary adrenal failure. From a CT scan-directed needle biopsy of the right adrenal mass and subsequent staging we were able to diagnose a primary bilateral adrenal lymphoma, diffuse large B-cell type (REAL/WHO). On CHOP chemotherapy both adrenal masses decreased dramatically and the patient is in remission 18 months later. Primary adrenal lymphoma is a rare condition, since 65 cases have been reported to date. Histological diagnosis is nevertheless important, in view of the excellent response to specific therapy observed in some cases.

Adrenal Gland Neoplasms↗

Morphine-induced suppression of saccharin intake is correlated with elevated corticosterone levels.

Rats suppress intake of a saccharin conditioned stimulus (CS) when paired with a drug of abuse. This phenomenon, however, is not uniform across all subjects and is greater following exposure to stress and in animals that more readily self-administer drugs of abuse. The present study was designed to examine these individual differences in intake suppression following seven saccharin-morphine pairings. Plasma corticosterone also was evaluated both before and after conditioning in order to determine whether the magnitude of CS suppression is, or is not, related to circulating corticosterone levels. The findings indicated that, while all rats were exposed to the same number of saccharin-morphine pairings, only half of these animals actually suppressed intake of the saccharin CS. Moreover, the results showed that greater suppression of CS intake was associated with higher corticosterone levels at test (r=-0.84, P<0.0001). Taken together, the results demonstrate that individual differences affect not only the reduction in CS intake following taste-drug pairings, but also the associated cue-induced elevation in circulating corticosterone.

Animals↗

Metaiodobenzylguanidine assessment of metastatic neuroblastoma: observer dependency and chemosensitivity evaluation. The SFOP Group.

BACKGROUND: In children over 1 year of age with metastatic neuroblastoma, clearance of metaiodobenzylguanidine (MIBG) skeletal uptake after four courses of induction chemotherapy is one of the most powerful prognostic factors. How subjective is quantification of MIBG uptake, and can earlier MIBG scintigraphy separate good and bad responders? PROCEDURE: The data from 47 patients who received uniform induction therapy were reviewed. A novel scoring system of MIBG update intensity was proposed. Initial, intermediate (after two courses), and final (after four courses) intensities were scored (0 to 21 points) independently by six different observers. The initial global score and the relative score (calculated by dividing the global score after two courses by the initial score) were compared to the final score. Good responders were those who scored 0 at final MIBG. RESULTS: Between two observers, the correlation coefficient for the global score was superior to 0.80, in nine of ten comparisons established between observers 1-5. The initial score did not predict the final score insofar as only nine of fourteen patients with low initial scores were good responders. The relative score also failed to predict outcome; only six of ten patients with favorable relative score (i.e., <20%), were good responders. CONCLUSIONS: This scoring system is reliable and may be used in multicentric trials. However, both initial and relative scores failed to predict final outcome. Thus, intermediate MIBG may be omitted during induction therapy assessment.

3-Iodobenzylguanidine↗

Post-ECT agitation and plasma lactate concentrations.

This prospective study evaluated the hypothesis that emergence agitation after electroconvulsive therapy (ECT) could be caused by lactate-induced panic secondary to insufficient neuromuscular blockade. Plasma lactate levels were measured before and after 245 consecutive ECT sessions in 37 patients monitored for evidence of post-ECT agitation. ECT was administered using a brief-pulse, rectangular, constant-current device through bilaterally placed electrodes under general anesthesia and neuromuscular blockade. Agitation was observed in 7% of all ECT sessions. No significant difference could be found in pre-ECT lactate levels. However, mean post-ECT lactate levels in agitated sessions were significantly greater than those in nonagitated sessions (4.77 versus 2.54 mmol/l, p < 0.05). An increase (+27%) in the pre-ECT succinylcholine dose for those patients who previously had repeated post-ECT agitation resulted in cessation of post-ECT agitation and return of the formerly high post-ECT lactate levels to normal (1.61 versus 2.07 mmol/l). Although the number of patients who had post-ECT agitation was small, the data support the hypothesis that post-ECT agitation might be a manifestation of lactate-induced panic.

Adolescent↗

Effects of androgen treatment on expression of macrophage Fcgamma receptors.

Macrophage Fcgamma receptors (FcgammaRs) play an important role in the host defense against infection and in the pathophysiology of immune cytopenias. Modulation of macrophage FcgammaR expression is a potential therapeutic approach to immune disorders. Glucocorticoids and progesterones decrease macrophage FcgammaR expression. We assessed the effect of treatment with androgens and antiandrogens on the expression of macrophage FcgammaRs using an experimental guinea pig model. Four androgens (testosterone, dihydrotestosterone, mesterolone, and danazol) and five antiandrogens (flutamide, nilutamide, cyproterone acetate, spironolactone, and finasteride) were studied. Following in vivo treatment of guinea pigs, we determined the clearance of immunoglobulin G (IgG)-sensitized erythrocytes in vivo, the binding of IgG-sensitized erythrocytes by isolated splenic macrophages, and splenic macrophage FcgammaR cell surface expression. All of the androgens impaired the clearance of IgG-sensitized erythrocytes by decreasing splenic macrophage FcgammaR expression. Dihydrotestosterone and mesterolone were more effective than testosterone or dihydrotestosterone. Flow cytometry and fluorescence microscopy with monoclonal antibodies demonstrated that the androgens decreased the cell surface expression of FcgammaR1,2 more than that of FcgammaR2. Antiandrogens did not significantly alter macrophage FcgammaR expression. Nevertheless, antiandrogens counteracted the effects of androgens on macrophage FcgammaR expression. These data indicate that androgens impair the clearance of IgG-coated cells by decreasing splenic macrophage FcgammaR expression. Thus, androgens other than danazol are candidate drugs for the treatment of immune disorders.

Androgens↗

Impact of targeting deviations on outcome in medulloblastoma: study of the French Society of Pediatric Oncology (SFOP).

PURPOSE: To correlate targeting deviation in external beam radiation therapy with site of relapse in a prospective study of 174 patients treated for medulloblastoma. METHODS AND MATERIALS: Between February 1992 and February 1998 the radiotherapy treatment records were reviewed by a panel of radiation oncologists for 174 children treated with radiation therapy for medulloblastoma. The review was done without knowledge of patient outcome. Patterns of relapse were correlated with the results of the quality control review. RESULTS: Among the 174 patients five relapsed before the start of radiotherapy. One hundred sixty-nine patients were evaluable for correlation between targeting deviation and site of relapse. Number of major deviations in radiation therapy treatment is strongly correlated with the risk of tumor relapse (67% [95% CI: 28-91] of 3-year relapse rate in patient group with 2 major deviations and 78% [95% CI: 35-96] with 3 major deviations). This is particularly correlated with relapse in the frontal region of the brain: 5 relapses occurred in the frontal region in patients with major deviation in this area. An erroneous choice of electron beam energy is also linked with craniospinal fluid (CSF) relapse (3-year relapse rate of 68% [95% CI: 42-86]). Minor deviations in therapy technique are slightly associated with an increased risk of relapse in the same range as the group with only one major deviation. CONCLUSION: The quality of medulloblastoma radiation therapy technique is strongly correlated with outcome. Pretreatment central quality assurance review or standardized computer-designed blocks would improve survival to an extent equivalent to that attributed to adjuvant chemotherapy.

Adolescent↗

Nonmetastatic pelvic Ewing sarcoma: report of the French society of pediatric oncology.

BACKGROUND: Since January, 1984, 59 children with histologically confirmed Ewing sarcoma of the pelvic bone have been treated with three successive chemotherapy protocols recommended by the French Society of Pediatric Oncology. The purpose of the current study was to evaluate the role of surgery and/or radiotherapy in local progression-free, disease-free, and overall survivals (LPFS, DFS, and OS, respectively). PROCEDURE: We retrospectively examined 59 children treated for nonmetastatic, pelvic Ewing sarcoma over the last 12 years. All were first treated with chemotherapy according to the current French protocol. Six patients developed progressive disease before local treatment and were excluded for local control and survival analysis. Local treatment was surgery alone in 17 cases, radiation therapy in 27 cases, and surgery plus radiation therapy in 9 cases. RESULTS: With a median of follow-up of 6.5 years, no significant differences in local control or survival were observed with the three chemotherapeutic protocols. Of the 53 patients evaluable for local control, 6 relapsed locally only, 8 had local and distant relapses, and 9 had distant metastases only. The 5-year OS rate was worst for patients with radiotherapy alone compared to those with surgery or combined modality treatment (44 % vs. 72 %, P = 0.043). The 5-year LPFS and DFS rates were worst in the radiotherapy-alone group but not significantly (63% vs. 79%, P = 0. 22 and 42% vs 71%, P =0.07, respectively). The importance of surgery to OS and DFS was confirmed by multivariate analysis (P = 0.026 and P = 0.048, respectively). One surviving patient was diagnosed with in-field fibrosarcoma, which was presumably radiation induced. CONCLUSIONS: Despite intensive, multiagent chemotherapy, survival from pelvic Ewing sarcoma has not improved over the past decade; however, the survival rate does not seem to be worse than that from Ewing sarcoma at other locations, insofar as at least 50% of the patients were cured. Surgery or a combination of surgery and radiation therapy are the best local treatment; exclusive radiation therapy should be reserved for patients with inoperable lesions or partially or nonchemosensitive tumors or when surgery would be an amputation.

Adolescent↗

Macrophage Fcgamma receptors expression is altered by treatment with dopaminergic drugs.

Macrophage Fcgamma receptors have an important role in host defense and the pathophysiology of immune mediated disorders. Alteration of splenic macrophage Fcgamma receptors expression predisposes to severe infection. Inhibition or blockade of splenic macrophage Fcgamma receptors is one of the mechanisms by which immune cytopenias improve. Dopaminergic drugs have clinically significant regulatory functions on the immune response. Using an experimental model in the guinea pig we assessed the effect of commonly used dopaminergic drugs on the expression of macrophage Fcgamma receptors. Three dopa-antagonists, bromocryptine, leuprolide, and pergolide, and seven dopa-antagonists, chlorpromazine, SCH 23390, metochlopramide, sulpiride, veralipride, alizapride, and cisapride, were studied. Following guinea pig treatment with dopaminergic drugs, the clearance of IgG-sensitized RBCs in vivo, the in vitro binding of IgG-sensitized RBCs by isolated splenic macrophages and flow cytometry with monoclonal antibodies were performed. Treatment with dopa-agonists enhanced the clearance of IgG-sensitized RBCs, the in vitro binding of IgG-sensitized RBCs by isolated splenic macrophages, and the cell surface expression of both macrophage Fcgamma receptors, and vice versa, dopa-antagonists impaired macrophage Fcgamma receptors expression. Macrophage FcgammaR1,2 was more sensitive than FcgammaR2 to such dopaminergic effect. These alterations of macrophage Fcgamma receptors expression are mediated by both D1 and D2 dopamine receptors, with a major participation of D2 receptors. Dopaminergic drugs alter the clearance of IgG-coated cells by an effect at the expression of splenic macrophage Fcgamma receptors.

Animals↗

Bioremoval of organic and inorganic sulphur from coal samples

The microbial ecology of different Spanish coal samples has been studied. Several bacteria have been isolated from enrichment cultures and characterised and their biodesulphurization abilities evaluated. Using morphological and physiological properties, different isolates have been related to species of the Xanthomonas, Pseudomonas, Chryseomonas and Moraxella genera. Some of the isolates, B(30)15 and T(30)10, gave important levels of organic desulphurization, close to 70%. Other isolates, B(30)7 and B(30)8, were able to remove inorganic sulphur with high efficiencies, over 67%. One of the isolates, B(30)10, metabolically related to Xanthomonas maltophila, was able to remove both organic and inorganic sulphur at neutral pH, with efficiencies of 69% and 68% respectively. The results obtained underline the potential use of some of these strains for industrial coal desulphurization processes.

Journal Article↗

Nonfunctioning pituitary macroadenoma presenting with mild hyperprolactinemia and amenorrhea.

OBJECTIVE: To describe a patient with a clinically nonfunctioning pituitary macroadenoma who presented with mild hyperprolactinemia and amenorrhea. DESIGN: Case report. SETTING: Tertiary care medical facility. PATIENT(S): A 44-year-old woman with a 6-month history of amenorrhea. INTERVENTION(S): Pituitary testing, magnetic resonance imaging of the sella turcica, and transsphenoidal surgery. MAIN OUTCOME MEASURE(S): Pituitary function testing, magnetic resonance imaging, and return of menstrual cycles. RESULT(S): Baseline laboratory data revealed a serum prolactin level of 34 ng/mL (normal range, 3-20 ng/mL), normal thyroid function test results, and an FSH level of 6.7 mIU/mL. A second fasting prolactin level was 48 ng/mL. Magnetic resonance imaging of the sella turcica revealed a pituitary macroadenoma measuring 1.4 x 3.2 cm. Further testing of baseline pituitary function revealed normal findings. The patient underwent an uncomplicated transsphenoidal resection of the pituitary tumor and maintained normal pituitary function. Pathologic evaluation revealed a pituitary adenoma that stained positive for FSH and focally for the alpha subunit. The adenoma stained negative for GH, prolactin, ACTH, LH, and TSH. CONCLUSION(S): This patient had a nonsecreting gonadotroph macroadenoma that resulted in hypogonadotropic hypogonadism along with mild hyperprolactinemia, presumably secondary to interruption of normal transport down the pituitary stalk.

Adenoma↗

The suppressive effects of LiCl, sucrose, and drugs of abuse are modulated by sucrose concentration in food-deprived rats.

Suppression of intake of a gustatory conditioned stimulus (CS) occurs when paired with either an aversive or an appetitive unconditioned stimulus (US). Toxic substances, such as lithium chloride (LiCl), induce conditioned taste aversions while rewarding stimuli, such as high a concentration of sucrose, reduce intake through a comparison process referred to as anticipatory contrast. Drugs of abuse also suppress CS intake, but it is not known whether they do so via their rewarding or aversive properties. Using 0.1, 0.3, or 0.5 M sucrose solutions as the gustatory CS, we compared the suppressive effects of LiCl (5.29 mg/kg), morphine (15 mg/kg), cocaine (10 mg/kg), and a 1.0-M sucrose solution in rats that were food deprived. The doses of the three drugs have been equated in terms of their suppressive effects in water-deprived and free-feeding rats. The results showed that in food-deprived rats the sucrose US failed to suppress intake of any of the sucrose CSs, the drugs of abuse failed to suppress intake of the 0.3 and 0.5-M concentration of sucrose, and LiCl failed to suppress intake of the 0.5-M sucrose solution. When taken together, these findings reveal that the suppressive effects of all USs (aversive, appetitive, and drugs of abuse) can be offset by the use of a caloric CS when evaluated in food-deprived rats.

Analysis of Variance↗

A novel endothelial cell-based gene therapy platform for the in vivo delivery of apolipoprotein E.

A major focus in gene therapy has been the use of recombinant viruses to deliver genes in vivo. Although this approach shows much promise, there are many safety concerns associated with the use of viral materials in the treatment of human diseases. Our alternative cell-based gene therapy approach utilizes endothelial cells (Pro 175) isolated from the murine embryonic yolk sac. These endothelial cells were evaluated for their potential use in gene therapy as a gene delivery platform. As a test model, we used these cells to deliver apolipoprotein E (apoE) in the murine apoE knockout atherosclerosis model. The lack of apoE protein in these animals results in high levels of serum cholesterol and formation of severe aortic plaques and lesions at a young age. After transplantation of the apoE secreting Pro 175 endothelial cells into apoE-deficient mice, serum cholesterol levels were measured at 2 week intervals. During the 3 months after the initiation of these experiments, levels of cholesterol in the animals having received the apoE secreting endothelial cells were statistically lower compared with the levels of age-matched controls having received non-secreting endothelial cells. Concomitant with cholesterol reduction, atherosclerotic aortic plaques were noticeably reduced in the experimental apoE+ animals. These results highlight the potential of these unique endothelial cells as an efficient delivery platform for somatic gene therapy.

Animals↗

Systemically administered interleukin-10 reduces tumor necrosis factor-alpha production and significantly improves functional recovery following traumatic spinal cord injury in rats.

In these studies, we examined the neuroprotective effects of the potent antiinflammatory cytokine interleukin-10 (IL-10) following spinal cord injury (SCI). Neuroprotection was assessed by using behavioral and morphological end points. We hypothesized that injury-induced inflammation contributes to the resulting neuropathology and subsequent loss of function. Therefore, by attenuating injury-induced inflammation, we should promote functional recovery. The New York University device was used to induce moderate SCI and study the resulting inflammatory response and functional consequences of inhibiting this response in rats. We determined that SCI induces the expression of tumor necrosis factor-alpha (TNF-alpha) in the spinal cord and by SCI-activated monocytes isolated from the peripheral circulation. IL-10 (5.0 microg) administered 30 minutes after-injury significantly reduced the expression of TNF-alpha protein in the spinal cord and in vitro by SCI-activated monocytes. Next, we investigated whether IL-10 would improve functional recovery after SCI. Randomized, double-blinded studies demonstrated that a single injection of IL-10 significantly improves hind limb motor function 2 months after injury, as determined by the Basso, Beattie and Bresnahan (BBB) open-field behavioral test. IL-10-treated animals had a mean BBB score of 18.0+/-0.5 (SEM, n = 9) compared with a score of 12.9+/-0.6 (SEM, n = 9) for the saline-treated controls. Morphological analysis demonstrated that IL-10 reduces lesion volume by approximately 49% 2 months after injury. These data suggest that acute administration of IL-10 reduces TNF-alpha synthesis in the spinal cord and by activated macrophages, is neuroprotective, and promotes functional recovery following SCI.

Animals↗

Diagnosis, treatment, and outcome of pituitary tumors and other abnormal intrasellar masses. Retrospective analysis of 353 patients.

We reviewed the clinical features, essential laboratory data, pituitary imaging findings (computerized tomography and magnetic resonance imaging), management, and outcome of 353 consecutive patients with the presumptive diagnosis of pituitary tumor investigated from January 1984 through December 1997 at University Hospital, Lausanne, Switzerland. In 18 cases primary empty sella turcica was diagnosed, and in 13 cases of pseudacromegaly there were no endocrine abnormalities. The remaining 322 patients disclosed abnormal pituitary masses, including 275 pituitary adenomas, 18 craniopharyngiomas, 6 cases of primary pituitary hyperplasia, 6 intrasellar meningiomas, 6 cases of distant metastases, 4 intrasellar cysts, 2 chordomas, 1 primary lymphoma, and 1 astrocytoma. Biologic data and immunohistochemical analysis of the excised tissues demonstrated that prolactinomas and nonsecreting adenomas (NSAs) were the most frequent pituitary tumors (40% and 39%, respectively), followed by somatotropic adenomas with acromegaly (11%) and Cushing disease (6%). In contrast with the vast majority of NSAs, which significantly expressed glycoprotein hormones in tissue without secreting them, there was a small group of glycoprotein hormone-secreting adenomas (2%), which had a more severe clinical course after surgery. Thirty-eight pituitary masses were incidentally discovered, most of them NSAs. The expansion of pituitary adenomas into the right cavernous sinus was twice as frequent as to the left cavernous sinus. For the differential diagnosis of hyperprolactinemia, basal prolactin (PRL) levels above 85 micrograms/L, in the absence of renal failure and PRL-enhancing drugs, and a PRL increment of less than 30% after thyrotropin-releasing hormone (TRH) accurately ruled out functional hyperprolactinemia due to NSA, and were typical of prolactinomas. For screening and follow-up of acromegaly, basal growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, as well as the paradoxical GH response to TRH (present in 2/3 acromegalic patients), could be used as convenient tools, but the most accurate test for diagnosis and prediction of outcome after therapy was GH (lack of) suppression during oral glucose tolerance test. In Cushing disease, single evening plasma cortisol was as good as the overnight dexamethasone suppression test for screening, and a combined dexamethasoneovine corticotropin-releasing hormone (oCRH) test was as accurate as the long dexamethasone suppression test to confirm the diagnosis. Bilateral inferior petrosal sinus catheterization coupled with oCRH test confirmed the pituitary origin of excess adrenocorticotropic hormone (ACTH) in all patients, including those with normal pituitary on magnetic resonance imaging (50% of the cases). However, this procedure failed to predict tumor localization correctly within the pituitary in 21% of patients. Pituitary cysts, meningiomas, and craniopharyngiomas with an intrasellar component were correctly diagnosed based on pituitary imaging in 75%, 67%, and 44% of cases, respectively. The remainder, as well as the cases of pituitary hyperplasia, metastases, and other less frequent pathologies, were initially diagnosed as NSAs or as masses of unknown nature. When surgery was indicated, pituitary adenomas and other intrasellar masses were operated on by the transsphenoidal route, with the exception of 100% of meningiomas, 83% of craniopharyngiomas, and 10% of NSAs, which were operated on by the transcranial route. Favorable late surgical outcome of prolactinomas could be predicted by a restored PRL response to TRH. However, dopamine agonist (DA) therapy, usually resulting in satisfactory control of PRL levels and in tumor shrinkage, progressively displaced surgery as primary treatment for prolactinomas throughout the study period. After full-term pregnancy, the size of prolactinoma decreased in 7 of 9 patients, and PRL was normal in 2. Surgery was the first treatment for NSAs, with a tumor rela

Acromegaly↗

Complete hypogonadotropic hypogonadism associated with a novel inactivating mutation of the gonadotropin-releasing hormone receptor.

In this study, we describe a patient with a phenotype of complete hypogonadotropic hypogonadism who presented primary failure of pulsatile GnRH therapy, but responded to exogenous gonadotropin administration. This patient bore a novel point mutation (T for A) at codon 168 of the gene encoding the GnRH receptor (GnRH-R), resulting in a serine to arginine change in the fourth transmembrane domain of the receptor. This novel mutation was present in the homozygous state in the patient, whereas it was in the heterozygous state in both phenotypically normal parents. When introduced into the complementary DNA coding for the GnRH-R, this mutation resulted in the complete loss of the receptor-mediated signaling response to GnRH. In conclusion, we report the first mutation of the GnRH-R gene that can induce a total loss of function of this receptor and is associated with a phenotype of complete hypogonadotropic hypogonadism.

Adult↗

Food-dependent Cushing's syndrome: possible involvement of leptin in cortisol hypersecretion.

Stimulation ofcortisol secretion by food intake has been implicated in the pathogenesis of some cases of ACTH-independent Cushing's syndrome, via an aberrant response of the adrenal glands to gastric inhibitory polypeptide (GIP). We report here a novel case of food-dependent Cushing's syndrome in a patient with bilateral macronodular adrenal hyperplasia. In this patient we were able to confirm a paradoxical stimulation of cortisol secretion by GIP in vivo as well as in vitro on dispersed tumor adrenal cells obtained at surgery. In addition to GIP, in vitro stimulation of these cultured tumor adrenal cells with leptin, the secreted product of the adipocyte, induced cortisol secretion. By comparison, no such stimulation was observed in vitro in adrenal cells obtained from another patient with bilateral macronodular adrenal hyperplasia and Cushing's syndrome that did not depend on food intake, in tumor cells obtained from a solitary cortisol-secreting adrenal adenoma, and in normal human adrenocortical cells. These results demonstrate that as in previously described cases of food-dependent Cushing's syndrome, GIP stimulated cortisol secretion from the adrenals of the patient reported here. Therefore, they indicate that such a paradoxical response probably represents the hallmark of this rare condition. In addition, they suggest that leptin, which normally inhibits stimulated cortisol secretion in humans, participated in cortisol hypersecretion in this case. Further studies in other cases of food-dependent Cushing's syndrome, however, will be necessary to better ascertain the pathophysiological significance of this finding.

Adrenal Glands↗