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Biomedical subjects

J F Lopez

Publications and source records attributed to J F Lopez.

At least 19 recordsLinked to original sources

Dysregulation of the fibroblast growth factor system in major depression.

In this report we describe findings that imply dysregulation of several fibroblast growth factor (FGF) system transcripts in frontal cortical regions of brains from human subjects with major depressive disorder (MDD). This altered gene expression was discovered by microarray analysis of frontal cortical tissue from MDD, bipolar, and nonpsychiatric control subjects and was verified by quantitative real-time PCR analysis and, importantly, in a separate cohort of MDD subjects. Furthermore, we show, through a separate analysis of specific serotonin reuptake inhibitor (SSRI)-treated and non-SSRI-treated MDD subjects that the observed changes in expression of FGF transcripts are not secondary to drug treatment. Rather, changes in specific FGF transcripts are attenuated by SSRIs and may thus be partially responsible for the mechanism of action of these drugs. We also make available the gene-expression profile of all of the other growth factors and growth factor receptors detected in these postmortem samples.

Adult↗

Endoscopic retrograde cholangiopancreatography (ERCP) in pregnancy without the use of radiation.

BACKGROUND: Biliary disease in pregnancy is a relatively uncommon condition; the diagnosis of this condition is not standardized. Furthermore, the use of radiographic imaging studies and therapeutic approaches in pregnancy is limited because of the possibility of fetal exposure. STUDY DESIGN: During a 2-year interval of 2001 to 2002, we successfully performed endoscopic retrograde cholangiopancreatography (ERCP) studies in 6 pregnant women between 6 and 30 weeks of gestation with symptomatic acute cholangitis or pancreatitis without irradiation exposure or major maternal complications. Five of the women had classic symptoms of severe right upper quadrant abdominal pain, gallbladder stones, jaundice, and dilated bile ducts on ultrasonic evaluation. One woman had severe recurrent pancreatitis during early pregnancy 4 years after a cholecystectomy. The cases are compiled to provide a descriptive review of ERCP without the use of radiation imaging treatment for these conditions. RESULTS: Maternal outcome: After ERCP, jaundice resolved in all cases. No further episodes of pancreatitis occurred during the 1 affected pregnancy. No post-ERCP complications occurred during this series. Two patients required cholecystectomy later, one in the postpartum period and the other 5 weeks post-ERCP. Fetal outcome: Two infants were born at term without complications. Two infants were born prematurely at 35 weeks, 1 with significant growth retardation and pulmonary complications and 1 without developmental problems or complications. Two mothers were lost to follow-up; the outcomes of their pregnancies are unknown. CONCLUSION: The use of ERCP in pregnancy is limited because of the undesirable effects of radiation exposure to the fetus.

Adult↗

DNA microarray analysis of functionally discrete human brain regions reveals divergent transcriptional profiles.

Transcriptional profiles within discrete human brain regions are likely to reflect structural and functional specialization. Using DNA microarray technology, this study investigates differences in transcriptional profiles of highly divergent brain regions (the cerebellar cortex and the cerebral cortex) as well as differences between two closely related brain structures (the anterior cingulate cortex and the dorsolateral prefrontal cortex). Replication of this study across three independent laboratories, to address false-positive and false-negative results using microarray technology, is also discussed. We find greater than a thousand transcripts to be differentially expressed between cerebellum and cerebral cortex and very few transcripts to be differentially expressed between the two neocortical regions. We further characterized transcripts that were found to be specifically expressed within brain regions being compared and found that ontological classes representing signal transduction machinery, neurogenesis, synaptic transmission, and transcription factors were most highly represented.

Aged↗

Hormonal evidence for altered responsiveness to social stress in major depression.

In patients with major depression, abnormalities in baseline cortisol secretion and resistance to negative feedback are well established. However, it is unclear if patients with major depression have alterations in the hypothalamic-pituitary-adrenal (HPA) response to stressors. While other challenges to the HPA axis have used endocrine stimuli such as insulin-induced hypoglycemia, we now report of the response to a social stressor in patients with major depression and matched control subjects. We used the Trier Social Stress Test (TSST), a public speaking task followed by mental arithmetic challenge in front of a panel of judges. The results suggest that depressed patients manifest normal cortisol response to a social stressor, despite increased pre-stressor plasma cortisol. However, the beta-endorphin response to the TSST was significantly smaller in the depressed patients compared to matched controls. These data are similar to data found with exogenous corticotropin-releasing-hormone challenge studies and suggest that elevated baseline cortisol can modulate the pituitary corticotroph response to a stressor, but that changes in adrenal sensitivity to ACTH result in a robust cortisol response to this stressor.

Adult↗

Carbon isotope ratio monitoring-gas chromatography mass spectrometric measurements in the marine environment: biomarker sources and paleoclimate applications.

Some applications in the use of compound-specific isotopic analyses (CSIA) for biomarker source elucidation in the marine environment and its potential applications to paleoclimatology are evaluated in the present study. The potential use of the carbon isotope ratios of marine biomarkers as recorders of CO2 levels has been considered. A significant correlation between delta 13C cholesterol of suspended particulates and seawater CO2 concentrations from the south Indian Ocean has been found. delta 13C composition in biomarkers of different functionalities from three photosynthetic organisms has been examined. Small variations within and between biosynthetically related compound classes have been observed in cyanobacteria. In algae, e.g. diatoms and dinoflagellates, significant differences between the average delta 13C composition of fatty acids and sterols were observed (7.5/1000 and 2/1000, respectively). These differences can be attributed to diverse isotope effects associated with different biosynthetic reactions. Isotopic variations among homologues of the same lipid class have also been observed. In diatoms, variations were up to 5/1000 within each class of fatty acids and sterols and in the dinoflagellate species, these variations were lower than 3/1000. These differences, and particularly the intra-specific shifts in delta 13C lipid composition, must be considered for the correct interpretation of changes in delta 13C molecular signatures in the marine environment.

Animals↗

The role of mineralocorticoid receptors in hypothalamic-pituitary-adrenal axis regulation in humans.

In rodents, two types of glucocorticoid receptors, the mineralocorticoid (MR; type I) and the glucocorticoid (type II) receptors, have been demonstrated to play a role in hypothalamic-pituitary-adrenal (HPA) axis regulation. Because MR shows a very high affinity for cortisol, it has been suggested that MR plays an important role in restraint of CRH and ACTH secretion during the nadir of the circadian rhythm. Although a number of studies have established the importance of MR in rodents, the functional role of MR in humans has not been determined. These studies evaluated whether spironolactone, an MR antagonist, had a detectable effect on HPA axis regulation in humans, and whether the effect was greatest during the evening, when plasma cortisol concentrations are in the MR range. Compared to the placebo day, after a single dose of spironolactone at either 0800 or 1600 h, there is a significant increase in plasma cortisol, which is preceded by a rise in ACTH and beta-endorphin. A significant effect of spironolactone on cortisol secretion was demonstrated with no differences between the morning and evening. Because the effect of spironolactone on cortisol was short lived, a second experiment was conducted using two doses of spironolactone, again sampling in the morning and evening. After two doses of spironolactone, plasma cortisol levels showed a significant and sustained spironolactone-induced elevation for the entire sampling period. However, neither plasma beta-endorphin nor ACTH was increased compared to levels on the placebo day. These data suggest that MR appear to play a clear role in HPA axis regulation during the time of the circadian peak as well as the trough. Furthermore, MR blockade may affect the sensitivity of the adrenal to ACTH.

Adrenal Glands↗

Normal pituitary response to metyrapone in the morning in depressed patients: implications for circadian regulation of corticotropin-releasing hormone secretion.

Excess secretion of cortisol in depressed patients has been documented by a number of investigators, which is presumed secondary to increased corticotropin (ACTH) and ACTH-releasing hormone (CRH) secretion. To unmask the proposed increased central (CRH) drive, we administered metyrapone in the AM to 13 depressed and 13 age- and sex-matched normal control subjects. Metyrapone administration resulted in a prompt decrease in plasma cortisol and in an increase in 11-deoxycortisol, the inactive precursor, in all subjects. Both depressed patients and normal control subjects demonstrated clear increases in ACTH and beta-lipotropin/beta-endorphin production. There were no significant differences between patients and controls in any hormonal measures following metyrapone administration. These data suggest that: 1) in the absence of negative feedback (cortisol blockade), mildly to moderately depressed outpatients do not manifest increased central drive in the morning; and 2) the secretory capacity of the corticotropes do not differ between such depressed patients and controls.

Adrenocorticotropic Hormone↗

Serotonin transporter binding sites and mRNA levels in depressed persons committing suicide.

The serotonin transporter (5-HTT) has been found altered in postmortem brain samples from persons committing suicide, but the results of radioligand binding studies have been inconsistent. In the present series of experiments, autoradiographic radioligand binding and in situ hybridization techniques were utilized to examine 5-HTT function in the brains of 8 depressed subjects who had committed suicide, and matched controls. It was hypothesized that depressed subjects would demonstrate decreased numbers of 5-HTT binding sites and mRNA; however, [125I]RTI-55 binding to the 5-HTT was not different in the midbrain, hippocampus, or frontal cortex of depressed subjects. Also, 5-HTT mRNA levels in dorsal and median raphe nuclei were not different between controls and depressed subjects. The current results, although limited in scope because of the small number of subjects included, offer no evidence that alterations in the 5-HTT occur in pertinent brain regions of depressed individuals.

Adult↗

Glucocorticoid regulation of hippocampal oxytocin receptor binding.

The effects of glucocorticoid hormones on oxytocin receptors in rat hippocampus were investigated. Oxytocin receptor autoradiography (using 0.1 and 1.2 nM concentrations of [125I]OVTA) revealed a significant (P < 0.02) decrease in oxytocin receptor binding in adrenalectomized animals 7 days after the surgery. Corticosterone replacement at the time of adrenalectomy prevented the decrease in oxytocin binding. The findings were significant in hippocampus and subiculum. These findings suggest regulation of oxytocin receptors, and possibly oxytocin-regulated behaviors by glucocorticoids.

Adrenalectomy↗

Quantitative analysis of the cardiac reserve.

OBJECTIVES: Analysis of the left ventricular (LV) pressure-volume loop (P-V loop) to assess LV function. DESIGN: Retrospective study of clinical, hemodynamic and angiographic data of 29 normal individuals and 115 patients with myocardial dysfunction, but no valvular or congenital heart disease. P-V loops were constructed, critically analyzed and compared with the clinical functional status of the patients. MAIN RESULTS: A number of theoretical new concepts was introduced and measured: end-systolic energy (ESE), total LV energy (TE) and potential maximal LV energy (PEmax). These variables were compared with the stroke work, which is neither sensitive nor specific, to separate different stages of cardiac function. ESE, TE and PEmax are sensitive variables, and inversely related to the cardiac reserve. CONCLUSIONS: P-V loops are easy to construct using well recorded hemodynamic and angiographic data. Analysis of P-V loops provides the cardiologist with an overall picture of the myocardial function and reserve.

Aged↗

Abnormalities of diastolic filling of the left ventricle associated with aging are less pronounced in exercise-trained individuals.

To determine whether exercise training has an effect on left ventricular diastolic dysfunction associated with the normal aging process, we studied a group of 20 normal healthy adult distance runners (mean miles currently run per week was 45 for an average of 15 years) and 20 normal healthy sedentary individuals (who currently walk less than 1 mile per day and are not involved in a regular exercise program) matched for age and systolic and diastolic blood pressure with the runners. Doppler echocardiographic indices of left ventricular diastolic filling were significantly different between the two groups. The exercise group when compared with the sedentary group had significantly decreased late diastolic peak filling velocity (0.51 +/- 0.11 m/sec versus 0.66 +/- 0.20 m/sec; p = 0.003), late diastolic velocity-time integral (5.2 +/- 1.5 cm versus 6.6 +/- 2.2 cm; p = 0.02), increased early-to-late peak filling velocity ratio (1.29 +/- 0.38 versus 0.96 +/- 0.24; p = 0.001), and early-to-late velocity-time integral ratio (2.08 +/- 0.51 versus 1.42 +/- 0.47; p less than 0.001). We conclude that the left ventricular diastolic dysfunction associated with "normal" aging is less pronounced in those persons who are exercise-trained.

Aging↗

Multiple steroid hormone levels in depressed patients and normal controls before and after exogenous ACTH.

Forty depressed patients and 36 age- and sex-matched controls were given 250 micrograms ACTH1-24 by IV bolus. Plasma steroid hormone levels were measured prior to and 60 min after ACTH administration. The depressed patients had significantly greater cortisol (F), 11-deoxycortisol (S), androstenedione (AD), and 17 alpha-hydroxyprogesterone (17 alpha-OHP) responses (delta; p less than 0.05) and a marginally greater 11 beta-hydroxyandrostenedione (11 beta-OHAD) response (delta; p = 0.091) than the controls. There was no significant difference in the corticosterone (B) response between the two groups. With the exception of 11 beta-OHAD, all the steroid hormones were significantly negatively correlated with age in the controls, but only S and AD marginally demonstrated this relationship in the depressed patients. F, S, AD, 17 alpha-OHP, and B, but not 11 beta-OHAD, were significantly positively correlated with each other in the controls, but only F was significantly correlated with AD in the depressed patients. These data suggest that the hypercortisolemia found in some depressed patients involves increased precursor and metabolite levels both at baseline and in response to exogenous ACTH, compared to controls. Furthermore, variability in these precursors is greater in depressed patients, and their relationship to age is lost. These findings are consistent with the hypothesis that adrenal products other than cortisol also could be related to affective symptoms.

17-alpha-Hydroxyprogesterone↗

[Malignant degeneration on ileostomy for rectocolonic polyposis].

One case of malignant degeneration on an ileostomy following proctocolectomy for familial intestinal polyposis is reported. On the basis of a review of the literature, the nosological context of this disease, the etiopathogenesis of cancerization and the surgical consequences are determined.

Adenocarcinoma↗

Detection and quantification of aortic regurgitation during aortic valvuloplasty.

The degree of aortic regurgitation, before and after balloon aortic valvuloplasty, was assessed in 32 patients, using double indicator dilution curves: a) the forward curve was obtained by dye injection into the left ventricle and sampling in the aorta; b) the regurgitant curve was obtained by dye injection in the aorta and sampling in the left ventricle. A regurgitant index (RI) was calculated by obtaining the ratio of the areas of the triangles from regurgitant and forward curves. Eight-five percent of the patients were 70 years or older. After valvuloplasty, aortic valve area increased from 0.5 +/- 0.3 cm2 to 0.7 +/- 0.3 cm2 (P = .0002) while left ventricular to aortic gradient decreased from 77 +/- 32 to 51 +/- 24 (P = .0001). RI did not significantly change in 58% of patients, increased in 25%, and decreased in 15.2%. We conclude that in most patients undergoing aortic valvuloplasty, regurgitation does not change after the procedure. In some patients it may increase significantly, and in a few it may even decrease. Indicator dilution curves technique seems to provide a sensitive, accurate, and reproducible method to detect and quantify aortic incompetence before and after valvuloplasty.

Aged↗

[Acute pancreatitis and pregnancy. A recent case report].

The authors report a case of acute pancreatitis occurring at the end of pregnancy. Pancreatitis and pregnancy in association with one another is a very serious condition. Research of the literature shows that the maternal mortality is 37% and the perinatal mortality 37.9%. These results mean that it is very important to make the diagnosis as early as possible and to work out the treatment to be given after the Caesarean operation so as to minimise the ill effects for the mother and the infant. The diagnosis is made by ultrasound of the abdomen and the levels of the amylase in the blood. It is possible to work out a correct management for these patients. The first priority is to deliver the fetus as soon as possible after the 34th week of amenorrhoea. The treatment should be multi-disciplinary and at the Caesarean there should be present an obstetrician, a surgeon who specialises in bowel conditions, a gastroenterologist and a neonatologist.

Acute Disease↗

The Kiricuta procedure in reconstructive surgical treatment of the breast.

A series of 50 patients with carcinoma of the breast underwent omental transposition. This palliative procedure is indicated for recurrences after conservative treatment, radiation necrosis and Stage III or IV ulcerated tumors. The operative technique is described in detail. Omentoplasties were performed upon 33 right and 17 left mammary areas. Forty-five right pedicled flaps and only four left areas were used. One patient died on the fourth postoperative day because of massive pulmonary embolus. Local repair was satisfactory in 76 per cent of the patients. Four patients presented with herniation of the abdominal wall at the site of omental tunneling. In three, the treatment consisted of sectioning the vascular pedicle and reinforcing the parietal closure with Dacron (polyester fiber) mesh.

Adult↗