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Biomedical subjects

M Fernandez

Publications and source records attributed to M Fernandez.

At least 19 recordsLinked to original sources

Influence of lighting conditions on toxicity and genotoxicity of various PAH in the newt in vivo.

We evaluated the influence of near-ultraviolet light (UVA) on the cytotoxicity and genotoxicity of 7 polycyclic aromatic hydrocarbons (PAH) in larvae of the amphibian Pleurodeles waltl. Benz[a]anthracene (BA), 7,12-benz[a]anthraquinone (BAQ) and anthracene (Ac) proved to be lethal at low doses (some ppb), and the following order of genotoxicity was observed: BA approximately BAQ > DMBA > DMA (9,10-dimethylanthracene). Ac, AQ (9,10-anthraquinone) and DBA (dibenz[a,h]anthracene) were not found to be clastogenic. In the larvae reared in normal conditions (subdued natural daylight/darkness alternation) or in continuous darkness, the BA derivatives were shown to be more genotoxic than BA itself: DMBA > BAQ > BA; BA (> or = 187.5 ppb) slightly increased the level of micronuclei in circulating erythrocytes, while DMBA was strongly clastogenic, in line with their reported carcinogenicity. In other experiments, rearing media alone (i.e., water containing BA, BAQ or DMBA) were UVA-irradiated for 24 h, and then tested on larvae in the dark ('IR-UV/dark' conditions). Photodegradation of BA (50 and 100 ppb) gave rise to clastogenic products. By contrast, DMBA (12.5, 25 or 50 ppb) was destroyed by UVA, and we suggested that any potentially mutagenic photoproducts formed were not in sufficient amounts to yield a positive response in the newt micronucleus test.

9,10-Dimethyl-1,2-benzanthracene

Diminished anticoagulant and fibrinolytic activity following liver transplantation.

This study analyzed the coagulation changes in twenty patients after orthotopic liver transplantation. The procoagulant, anticoagulant, and fibrinolytic systems were studied during the first two postoperative weeks. Within the first postoperative day all extrinsic and intrinsic pathway factors became normal except factors IX, VII, and X, which recovered within the next 24 hr. Of interest are the changes in factor VIII, which reached a high concentration with an increase in its antigenic fraction during the study. However, coagulation inhibitors showed a different pattern. In fact, antithrombin III (AT-III) and protein C (PC) needed from 7 to 14 days to reach normal values. Total protein S (TPS) and free protein S (FPS) did not recover until day 7, whereas heparin cofactor II (HC-II) remained at subnormal levels throughout the study. Thrombin-antithrombin III complex (TAT) values were strikingly elevated in the immediate postoperative period. Fibrinolysis parameters showed plasminogen (PL) levels in the normal range until day 4. Antiplasmin (AP) followed a curve parallel to that of plasminogen but its levels were higher during this observation period. Similarly the initial elevation in plasminogen activator inhibitor 1 endothelial type (PAI-1) levels remained high until days 4 and 7. In summary, it can be concluded that during the postoperative phase after OLT a hypercoagulable state is developed as a result of diminished anticoagulant and fibrinolytic activity. This coagulation might be a nontechnical factor contributing to the thrombotic vascular complications of some liver recipients.

Adolescent

Protein C, protein S and C4b-binding protein in neonatal severe infection and septic shock.

We have studied the behaviour of total protein S, free protein S, protein C and C4b-binding protein fifteen neonates with severe infections, eight with septic shock and in a group of ten healthy newborns. Protein C was decreased in shock and septic patients, but only the shock group showed significant differences compared to normal neonates. Total protein S was normal in both groups of patients, although free protein S had significantly lower values in shock and nonshock infants. C4b-binding protein was higher than normal in septic and shock patients compared to the control group. Decreased values of protein C and free protein S can be explained by the activation of coagulation and their subsequent consumption. On the other hand, the increased levels of C4b-binding protein can affect the distribution of protein S in plasma, producing a shift in protein S to the complexed inactive form. These findings can contribute to an increased risk of microthrombosis during neonatal sepsis.

Carrier Proteins

Foraging profiles of sympatric lowland gorillas and chimpanzees in the Lopé Reserve, Gabon.

Comparison of the diets of sympatric gorillas and chimpanzees allows an analysis of niche separation between these two closely related species. Qualitatively, their diets are similar, being dominated by an equally diverse array of fruit species complemented with vegetative plant parts, seeds and insects. Gorillas eat more vegetative plant parts than do chimpanzees, but niche separation is most obvious in periods of fruit scarcity when the two species show different strategies that reduce competition for food. Their abilities to overcome mechanical and physical plant defences appear to differ, as gorillas are able to subsist entirely on abundant vegetative foods. Chimpanzees show social adjustment, foraging alone or in small groups, to reduce intra-specific competition for scarce fruit resources. Thus it seems that subtle physiological differences have far-reaching repercussions, defining potential evolutionary pathways for social organization and allowing sufficient niche separation between species.

Animals

Group cognitive and behavioural treatment for hypochondriasis.

OBJECTIVE: To assess the feasibility of carrying out group cognitive and behavioural treatment for hypochondriasis in a general hospital setting. DESIGN: Assessment of patients referred for therapy. SETTING: District general hospital. PATIENTS: Six patients aged 35 to 55 (mean 43) years with a mean duration of symptoms of 12 years who fulfilled the Diagnostic and Statistical Manual for Mental Disorders (DSM III-R) criteria for hypochondriasis. MAIN OUTCOME MEASURES: Number of visits to their doctors, time spent thinking about illness, and scores on the hospital anxiety and depression scales. RESULTS: The mean number of visits to a doctor fell significantly after treatment (3 before treatment v 0.8 after treatment; p = 0.03) as did the time spent thinking about illness (57.3 v 40.6; p = 0.14). The depression and anxiety scores also fell, although the differences were not significant (depression: 9.5 before v 8.5 after; anxiety: 13 before v 12 after). CONCLUSION: It is feasible to carry out group cognitive and behavioural treatment in patients with hypochondriasis, and controlled studies are now indicated.

Adult

A sensitive fluorescence assay for quantitation of fludarabine and metabolites in biological fluids.

Rapid and quantitative dephosphorylation of the new anticancer nucleotide analogue fludarabine phosphate to its nucleoside 9-beta-D-arabinofuranosyl-2-fluoroadenine (F-ara-A) renders this metabolite the target for pharmacologic investigations. At clinically effective doses of fludarabine phosphate (18-30 mg/m2 per day) comprehensive pharmacokinetic analysis of F-ara-A has been limited by the sensitivity of UV based HPLC assays. To address this problem we developed a sensitive test based on the condensation of F-ara-A with chloroacetaldehyde to form the fluorescent derivative, arabinosyl-1,N6-etheno-isoguanine. Combined with a solid-phase extraction step prior to derivatization and separation of the reaction products by reverse-phase HPLC, this assay had a quantitation limit of 2 pmol F-ara-A per ml plasma. Slightly modified, the system was also applicable to urine specimens, with a quantitation limit of 1 nmol F-ara-A per ml urine.

Antimetabolites, Antineoplastic

Diagnostic potential of IgA coated Candida cells in mucous membrane candidiasis.

The significance of in vivo IgA coated yeast cells for the diagnosis of candidiasis of the oral and vaginal mucosal membranes was evaluated by direct immunofluorescence in 70 patients with or without clinical symptoms, shown to be positive for yeast growth in the cultural test. Most of the patients with clinically suspected candidiasis of the mucosal membranes gave positive results by serologic assays in contrast to the majority of symptomless patients. The diagnostic approach proved to be essentially consistent with the clinical signs, persistence of infection, response to antifungal therapy and quantitative cultural data.

Candida

Platelet [3H]imipramine binding in migraine and tension headache in relation to depression.

Platelet [3H]imipramine binding was measured in 40 migrainous (7 classical and 33 common) and 17 tension headache patients and in 28 normal controls. A significant reduction in Bmax was found in migraine compared with controls (p less than 0.05) but not in tension headache. In migraine, there was no significant relationship between Bmax and depression or anxiety score on the self-rating Hospital Anxiety and Depression (HAD) Scale, suggesting that the reduction in Bmax is a concomitant of migraine itself rather than a manifestation of associated depression. Preliminary evaluation using the Schedule of Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) tended to confirm this conclusion.

Adult

The complete sequence of the group-specific antigen, VP7, of African horsesickness disease virus serotype 4 reveals a close relationship to bluetongue virus.

The complete sequence of the S7 RNA that codes for the major group-specific coat protein. VP7, of African horsesickness virus serotype 4 (AHSV-4) was determined from cDNA analyses and found to be 1179 nucleotides in length. One single open reading frame of 353 codons was observed defining a protein of Mr 38,107 with a net charge of -1.5 at neutral pH. Comparison of the AHSV-4 VP7 sequence with that of bluetongue virus serotype 10 revealed an overall similarity of 44%, with the amino- and carboxy-terminal regions exhibiting the greatest levels of homology. In addition, potential secondary structures of the terminal sequences of the S7 RNA segments of AHSV-4 and BTV serotypes 10, 13 and 17 are presented.

African Horse Sickness Virus

Analysis of human T-cell epitopes in the 19,000 MW antigen of Mycobacterium tuberculosis: influence of HLA-DR.

The potential number of T-cell epitopes in the 19,000 molecular weight (MW) antigen has been investigated using overlapping peptides which comprise the complete sequence. Sixteen potential epitopes could be deduced from the responses to these peptides by polyclonal T cells derived from 22 antigen-responsive donors. The majority of epitopes were not predicted by either of the major paradigms, the Rothbard motif and the amphipathic helix. A hierarchy of epitopes was indicated by the responses, which ranged from strong and frequent in the N-terminal region, to moderate or weak elsewhere. Some epitopes were restricted by single HLA-DR determinants, or families of determinants sharing structural features in common, whilst the two N-terminal peptides were recognized by donors with a diversity of DR types. The high degree of T-cell recognition of the N-terminal region may be of relevance to the design of a sub-unit vaccine capable of priming T cells against Mycobacterium tuberculosis.

Amino Acid Sequence

Atonic pupil: an unusual complication of cataract surgery.

Eight cases of atonic pupil, an unusual complication following cataract surgery, are presented. Six of the eyes involved had intracapsular cataract extraction and anterior chamber intraocular lens implantation; one case underwent extracapsular cataract extraction with a posterior chamber intraocular lens implantation; the other had an extracapsular procedure with no implant. The etiology is unknown, but we believe the most likely one is that the sodium hyaluronate used in all these patients caused a temporary reduction of the iris blood supply by mechanical factors or by a vasoconstriction induced by some toxicity of the material that produced a lesion on the iris sphincter.

Adult

High incidence of endogenous depression in migraine: confirmation by tyramine test.

Forty patients with migraine who were attending a specialist clinic were interviewed with the Schedule for Affective Disorders and Schizophrenia--Lifetime version. Sixteen (40%) had a history of major depression which was of endogenous type in 15, according to Research Diagnostic Criteria. The tyramine test, a previously established trait marker for endogenous depression, showed that the migraine group as a whole had significantly low values compared with 14 normal controls, due almost entirely to low values in the endogenous depressive subgroup; there were no differences between diet-sensitive and non-diet-sensitive migraine patients. Thus depression in patients with migraine seems unlikely to be secondary to migraine per se. A substantial subgroup of patients with migraine may possess an inherent predisposition to endogenous depression.

Adult

Pancreatic transplants: CT-guided biopsy.

With use of computed tomographic (CT) guidance, 10 biopsies of pancreatic allografts were performed in four patients to determine the cause of pancreatic dysfunction. All biopsies were performed with an 18-gauge biopsy needle and with use of a biopsy gun. On four occasions, simultaneous biopsies of the pancreatic head and tail were performed. In nine of the 10 biopsies, specimens obtained were adequate for diagnosis. In two of the four simultaneous procedures, important histologic differences were noted between specimens from the head and those from the tail of the allograft. No complications occurred. These findings demonstrate the ease, accuracy, and safety of CT-guided biopsies of pancreatic transplants with a biopsy gun. Simultaneous sampling of the pancreatic head and tail may provide important clinical information that may not be available when the usual cystoscopically guided biopsy of the pancreatic head is used.

Biopsy, Needle

Serospecific protection of mice against intranasal infection with Bordetella pertussis.

The ability of purified serospecific agglutinogens from Bordetella pertussis to protect mice against intranasal infection has been examined. Immunization with agglutinogen 2 protected mice against infection with 1.2.0 or 1.2.3 serotypes of B. pertussis, whereas immunization with agglutinogen 3 protected mice against infection with all serotypes. More importantly immunization with serospecific agglutinogen resulted in immune selection so that organisms recovered following infection did not express the immunizing antigen. The results are consistent with the suggestions that protection of children with whole cell pertussis vaccine is to some extent serospecific and that agglutinogens should be considered as constituents of acellular pertussis vaccines.

Administration, Intranasal

Use of newt larvae for in vivo genotoxicity testing of water: results on 19 compounds evaluated by the micronucleus test.

The micronucleus test using erythrocytes of Pleurodeles waltl larvae (Amphibian, Salamandridae) was used to detect the genotoxic activity of various substances. Most of them were known (or suspected) to be mutagenic or carcinogenic in mammals. Larvae were reared in water containing either a test chemical (experimental group) or in control water and the levels of micronucleated red blood cells (RBCs) compared between the two groups. Aroclor 1254, butylated hydroxyanisole, phenobarbital and 12-O-tetradecanoyl-phorbol-13-acetate produced negative results, while acridine orange, benzo[alpha]pyrene, epsilon-caprolactam, cyclophosphamide, diethyl sulphate, epichlorhydrin, ethidium bromide, ethyl methanesulphonate, ethylene dibromide (dibromoethane), N-ethyl-N'-nitro-N-nitrosoguanidine, N-ethyl-N-nitrosourea, hexamethylphosphoramide, 3-methyl cholanthrene, pyrene and o-toluidine gave positive responses. The results were compared with published data from other tests used to detect the clastogenic or mutagenic properties of chemicals. We suggest that the newt micronucleus test could be used to monitor aquatic pollution, and/or for the quality control of drinking water. Pleurodele larvae may also prove to be of value for the detection of carcinogenic/clastogenic substances dissolved in water.

Animals

Tyramine sulfoconjugation in relation to depression in migraine. A pilot study.

Tyramine sulfoconjugation following an oral tyramine load was determined in 30 patients suffering from migraine and 14 controls not regularly suffering from headache. Reduced tyramine sulfoconjugation was found in those patients with a history of major depressive disorder compared with controls. When the patients with a history of major depression were removed from the analysis, no differences were found between diet-sensitive and non-diet sensitive migraine patients and controls.

Depression