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Biomedical subjects

M Fernandez

Publications and source records attributed to M Fernandez.

210 records · Page 12Linked to original sources
PubMedDate not supplied

Neural sensitization model for multiple chemical sensitivity: overview of theory and empirical evidence.

This paper summarizes theory and evidence for a neural sensitization model of hyperresponsivity to low-level chemical exposures in multiple chemical sensitivity (MCS). MCS is a chronic polysymptomatic condition in which patients report illness from low levels of many different, structurally unrelated environmental chemicals (chemical intolerance, CI). Neural sensitization is the progressive host amplification of a response over time from repeated, intermittent exposures to a stimulus. Drugs, chemicals, endogenous mediators, and exogenous stressors can all initiate sensitization and can exhibit cross-sensitization between different classes of stimuli. The properties of sensitization overlap much of the clinical phenomenology of MCS. Animal studies have demonstrated sensitization to toluene, formaldehyde, and certain pesticides, as well as cross-sensitization, e.g., formaldehyde and cocaine. Controlled human studies in persons with self-reported CI have shown heightened sensitizability in the laboratory to nonspecific experimental factors and to specific chemical exposures. Useful outcome measures include spectral electroencephalography, blood pressure, heart rate, and plasma beta-endorphin. Findings implicate, in part, dopaminergic mesolimbic pathways and limbic structures. A convergence of evidence suggests that persons with MCS or with low-level CI may share some characteristics with individuals genetically vulnerable to substance abuse: (a) elevated family histories of alcohol or drug problems; (b) heightened capacity for sensitization of autonomic variables in the laboratory; (c) increased amounts of electroencephalographic alpha activity at rest and under challenge conditions over time. Sensitization is compatible with other models for MCS as well. The neural sensitization model provides a direction for further systematic human and animal research on the physiological bases of MCS and CI.

Autonomic Nervous System↗
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EEG sensitization during chemical exposure in women with and without chemical sensitivity of unknown etiology.

This study tested the sensitization model proposed by Bell et al. [Bell I.R., Miller C.S. and Schwartz G.E. An olfactory-limbic model of multiple chemical sensitivity syndrome: possible relationship to kindling and affective spectrum disorders. Biol. Psychiatry 1992: 32: 218-242] to study chemical sensitivity. The sensitization model indicates that a pharmacological stimulus or a traumatic event which elicits a strong response can sensitize limbic and/or mesolimbic pathways; and subsequent less intense trauma or stimuli, in the same or different modality, can elicit an amplified response. Three groups of subjects were tested: (1) women who reported chemical sensitivity and no sexual abuse (chemically sensitive, CS); (2) sexually abused (SA) women without chemical sensitivity; and (3) healthy women without chemical sensitivity or sexual abuse history (normal, N). All subjects were exposed to odorant and nonodorous control stimuli once a week for 3 weeks. Electroencephalographic activity was recorded while subjects sniffed the odorant and control stimuli. Results of the study revealed that both the CS and the SA group showed electroencephalogram (EEG) alpha sensitization across experimental sessions, while the N group showed little change over time. Additionally, EEG findings revealed that the CS group generated significantly greater alpha activity than the other two groups. Finally, while the groups were different on measures of psychological distress, these differences did not diminish the EEG findings. In summary, these findings suggest that intermittent exposure to chemicals elicits sensitization in CS and SA women without chemical sensitivity, supporting our expectations that chemical sensitivity is, in part, a manifestation of time-dependent sensitization (TDS). Additionally, these EEG findings indicate that CS women are unlike SA and healthy women in the amount of EEG alpha activity they generate. Finally, these findings indicate that psychological factors as assessed in this study do not explain electrophysiological differences between chemically and non-chemically-sensitive women.

Drug Hypersensitivity↗
PubMedDate not supplied

Norfloxacin monodose use in patients with cholera in Salta Argentina.

The use of monodose (800 mg) per os of Norfloxacin was evaluated in 32 patients with cholera at Salvador Mazza's Hospital, Salta, Argentina. It was considered the celerity in negativization of stool culture (100% of cases: 12 hours post administration), it efficiency along time (24/24 controlled patients were negative at 10th day) and MIC of isolated strains (100% of strains were sensitive: range 0.008 to 0.016 micrograms/ml). It was included oral administration of sorbitol 70% in peanut oil in order to study patients at 10th day's control. This method could be an alternative one in the study of asymptomatic carrier. Norfloxacin monodose shows good performance in early negativization of stool culture and it was also effective along the whole observation period, suggesting it could prevent carriage.

Adolescent↗
PubMedDate not supplied

Alcohol and smokeless tobacco effects on the CD-1 mouse fetus.

Tobacco products and alcohol are commonly used as nonmedicinal drugs by pregnant women, and both are known to cause various effects on the fetus and the newborn. The objective of this study was to examine the fetal effects of both drugs when administered individually and simultaneously to pregnant CD-1 mice at moderate dosages. Specifically, we wanted to determine whether or not the effect on the fetus of these two biologically active substances was additive, ameliorative, or synergistic. A total of 65 CD-1 dams were divided among four groups receiving either ST equivalent to 8 mg/kg nicotine, ethanol (ETOH) 1.8 g/kg, a combination of ST+ETOH in the same dosages, or D-glucose (controls and ST alone) to supply calories equivalent to the dose of ethanol. Mice were dosed three times per day on gestational days 6-15. On gestational day 17 all dams were killed, fetal and placental weights recorded, and the number of resorbed, dead, and malformed fetuses noted. The mean maternal plasma drug levels were: nicotine-321 ng/ml and ethanol-0.105 g%. No significant differences were observed in maternal weight gain, litter size, or in the incidence of resorptions, deaths and/or malformations. Fetal weights were reduced in all three treatment groups (P less than 0.05), with the greatest reduction (13% decrease) recorded in the ST group, followed by a 9% decrease in the ETOH group, and a 7% decrease in the ST+ETOH group. Placentas of the ST group weighed significantly less (P less than 0.05) than controls. Ossification of the fetal skeleton, observed in ten sites, was affected to the greatest extent in the ST group, followed by the ETOH and ST+ETOH groups. Craniofacial measurements were significantly affected (P less than 0.05) in all three treatment groups, compared to controls. We conclude that under these experimental conditions, in terms of fetal growth and ossification, ST had the greatest effect, followed by ETOH and ST+ETOH. The interaction of ST+ETOH was neither additive, synergistic, nor ameliorative.

Analysis of Variance↗
PubMedDate not supplied

Further experience with the syndromes produced by coca paste smoking.

Cocaine base or white coca paste was smoked heavily by 188 patients who came to four hospitals of Lima, Peru. The length of hospitalization varied from two days to six months. All patients were admitted because coca paste smoking had become a serious problem for their health or for social adjustment. Coca paste was smoked mixed with tobacco or marihuana. The main symptoms were anxiety mingled with euphoria and a rapidly developing compulsion to continue smoking. Frequently the patients developed irritability, illusions, hallucinations. When the use of the drug was heavy and continued for many hours or several days, the patients developed successively four stages of psychological reaction: euphoria, dysphoria, hallucinosis, and acute paranoid psychosis. The main symptoms and signs of all of these phases are discussed.

Adolescent↗
PubMedDate not supplied

EEG responses to low-level chemicals in normals and cacosmics.

Recent studies from the University of Arizona indicate that normal subjects, both college students and the elderly, can register the presence of low-intensity odors in the electroencephalogram (EEG) in the absence of conscious awareness of the odors. The experimental paradigm involves subjects sniffing pairs of bottles, one containing an odorant (e.g. isoamyl acetate) dissolved in an odorless solvent (water or liquid silicone), the other containing just the solvent, while 19 channels of EEG are continuously recorded. For the low-intensity odor conditions, concentrations are adjusted downward (decreased) until subjects correctly identify the odor bottle at chance (50%). The order of odorants, concentrations, and hand holding the control bottle, are counterbalanced within and across subjects. Three previous experiments found that alpha activity (8-12 hz) decreased in midline and posterior regions when subjects sniffed the low-intensity odors. The most recent study suggests that decreased theta activity (4-8 hz) may reflect sensory registration and decreased alpha activity may reflect perceptual registration. In a just completed experiment involving college students who were selected based on combinations of high and low scores on a scale measuring cacosmia (chemical odor intolerance) and high and low scores on a scale measuring depression, cacosmic subjects (independent of depression) showed greater decreases in low-frequency alpha (8-10 hz) and greater increases in low-frequency beta (12-16 hz) to the solvent propylene glycol compared to an empty bottle. Topographic EEG mapping to low-intensity odorants may provide a useful tool for investigating possible increased sensitivity to specific chemicals in chemically sensitive individuals.

Adolescent↗
PubMedDate not supplied

p53 oncoprotein as a prognostic indicator in patients with breast cancer.

UNLABELLED: p53 is a tumor suppressor gene located on the human chromosome 17 that is thought to regulate (suppress) the proliferation of normal cells. The mutant protein accumulates in the nuclei of tumor cells that may then have a proliferative advantage over normal cells. The purpose of this study was to investigate the relationship between levels of mutant p53 expression and the clinical outcome of patients with node-positive and node-negative breast cancer. Expression of mutant p53 was evaluated in 655 human breast carcinomas (349 node-positive and 306 node-negative patients) with long-term clinical follow-up by immunohistochemistry in sections from paraffin embedded tumors. RESULTS: Immunoreactivity was found in 37.3% of breast tumors. There was no significant correlation between the expression of p53 and tumor size, nodal involvement, age or histological type. However, p53 overexpression was clearly related to histological grade and steroid receptors, with a trend to higher overexpression in ER-tumors or in those with a high histological grade (p < 0.01). On univariate analysis positive tumors were associated with reduced DFS in the total group (p < 0.001) as well as in node-positive patients (p < 0.05) and in node-negative patients (p < 0.01). In conclusion, these results suggest that the immunoreactivity of p53 may be a biologic marker of prognostic significance in both node-positive and node-negative patients.

Biomarkers, Tumor↗
PubMedDate not supplied

Analysis of DNA methylation processes related to the inhibition of DNA synthesis by 5-azacytidine in Streptomyces antibioticus ETH 7451.

5-Azacytidine inhibits DNA synthesis and to a lesser proportion RNA synthesis in S. antibioticus. The biosynthesis of proteins is not affected. The main inhibitory effect of 5-azacytidine on DNA and RNA synthesis is probably caused by its incorporation into newly synthesized DNA or RNA and the formation of covalent complexes between cytosine-specific methyltransferases and the modified DNA or RNA templates. To analyze whether such effects could occur at the oriC region of S. antibioticus we analyzed the methylation status of this region using the bisulphite assisted genomic sequencing method. One of the cytosine residues found to be partially methylated was contained within an unique NaeI sequence (GCCGGC) in oriC. Subsequent analysis shows chromosomal DNA from S. antibioticus to be resistant to R.NaeI restriction indicating that this strain contains a NaeI-specific cytosine C5-methyltransferase activity. Following 5-azacytidine treatment the NaeI site within the oriC region becomes partially demethylated. Our results suggest that some of the 5-azacytidine effects on DNA and RNA synthesis might indeed be related to the complex formation and inhibition of a cytosine-specific DNA methyltransferase.

Azacitidine↗