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Biomedical subjects

P Fournier

Publications and source records attributed to P Fournier.

At least 19 recordsLinked to original sources

Excitation Gap in the Normal State of Underdoped Bi2Sr2CaCu2O8+delta

Angle-resolved photoemission experiments reveal evidence of an energy gap in the normal state excitation spectrum of the cuprate superconductor Bi2Sr2CaCu2O8+delta. This gap exists only in underdoped samples and closes around the doping level at which the superconducting transition temperature Tc is a maximum. The momentum dependence and magnitude of the gap closely resemble those of the dx2-y2 gap observed in the superconducting state. This observation is consistent with results from several other experimental techniques, which also indicate the presence of a gap in the normal state. Some possible theoretical explanations for this effect are reviewed.

Journal Article

Methyl iodide poisoning: report of two cases.

Two workers were poisoned following exposure to methyl iodide with inadequate protective devices. Their cases are presented together with a review of literature. Both patients developed symptoms and signs of cerebellar lesions and damage of the third, fourth, or sixth cranial nerve pathways. Spinal cord lesions producing motor and sensory disturbances were present in one. Late psychiatric disorders were observed in both patients. Although these symptoms were very similar to those reported in the nine published cases of methyl iodide poisoning, the toxicological diagnosis was delayed in one case: as repeated overexposure produced recurrent attacks of multifocal neurological dysfunction, multiple sclerosis was initially diagnosed, although several of the features observed are unusual in this disease. The manifestations of methyl iodide poisoning are similar to those of intoxication with other monohalomethanes. All these compounds probably share the same mechanisms of action. This mechanism and its therapeutic consequences are discussed.

Abducens Nerve

Differential activation of T cells by antibody-modulated processing of the flanking sequences of class II-restricted peptides.

Despite poor presentation of measles virus (MV) nucleoprotein (NP) by MHC class II of infected cells, NP-specific antibodies are one of the hallmarks of the early immune response against this virus. To study the influence of antibodies on processing and presentation of NP to three different T cell hybridomas, mAb recognizing distinctive llnear NP epitopes were developed. Two T cell hybridomas TNP408B and TNP408 reacted with the same core epitope of NP (amino acids 383-391), but differed in their sensitivity to the flanking sequences of peptides containing this epitope. TNP408B reacted with minimal concentrations of NP when this was complexed with mAb BNP146. NP alone or saturating concentrations of other mAb did not activate this T cell. Both T cells, TNP408 and TNP408B, were similar in their sensitivity to NP in the presence of saturating concentrations of BNP146 or of appropriate peptide (NP379). TNP408 did not differ from another T cell hybridoma (TNP79) in its sensitivity to different mAb, suggesting a specificity-dependent and a specificity-independent effect of mAb. Antibody-mediated activation was attributed to FcR-mediated uptake independent of the fine specificity of the mAb. In the case of TNP408B, this effect was further enhanced by a specific effect of BNP146. While all NP-specific mAb were sufficient to enhance presentation to TNP408 and TNP79 of their respective peptides derived from processed NP, BNP146 was necessary to generate the peptides with the proper flanking sequences required by TNP408B. Since the binding site of BNP146 coincides with the T cell epitope of TNP408B (and TNP408) it is suggested that binding of this mAb modulates processing of the flanking sequences of the peptides corresponding to this epitope. This study shows that antibodies can influence the T cell response to an antigenic protein quantitatively and qualitatively by taking advantage of the sensitivity of T cells to flanking sequences of class II-restricted peptides.

Amino Acid Sequence

Protection against measles virus encephalitis by monoclonal antibodies binding to a cystine loop domain of the H protein mimicked by peptides which are not recognized by maternal antibodies.

After immunization with measles virus (MV) several monoclonal antibodies (MAbs) were obtained, which reacted with peptides corresponding to the amino acids 361-410 of the haemagglutinin protein (MV-H). Three of these MAbs (BH6, BH21 and BH216) inhibited haemagglutination, neutralized MV in vitro and protected animals from a lethal challenge of rodent-adapted neurotropic MV. These MAbs reacted with the 15-mer peptides H381 and H386 defining their overlapping region 386-395 as a sequential neutralizing and protective epitope, which can be imitated by a short peptide. H381 and H386 share two Cys residues (C(386)KGKIQALC(394)ENPEWA) and for optimal MAb binding of peptide (or MV) disulphide bonds were required in addition to a linear C-terminal extension. Other MAbs bound to peptides C- (BH147, BH195) and N-terminally (BH 168, BH 171) adjacent to the loop but did not neutralize or protect. When sera from measles patients or from women of child-bearing age were tested with the peptides corresponding to this haemagglutinating and neutralizing epitope (HNE), none of the sera recognized the 15-mer peptides of this region, while some reactivity was found to 30-mers homologous to different wild-type mutants. Its lack of recognition by maternal antibodies and its high degree of conservation would make the HNE loop an attractive candidate to include into a subunit vaccine, which could be administered during early childhood, independent of immune status.

Amino Acid Sequence

Transesophageal echocardiography for the diagnosis and management of nonobstructive thrombosis of mechanical mitral valve prosthesis.

BACKGROUND: Diagnosis of a mechanical mitral valve prosthesis thrombosis is currently made with transthoracic Doppler echocardiography and occasionally with fluoroscopy. However, identifying a thrombus on a valve prosthesis may be difficult, especially if the thrombus is nonobstructive. To prospectively define the role of transesophageal echocardiography for identification of nonobstructive thrombi, we studied a series of patients in whom the prosthetic valve was considered to function normally on clinical examination and transthoracic echocardiography. METHODS AND RESULTS: One hundred fourteen consecutive patients with mechanical mitral valve prosthesis were investigated by both transthoracic echocardiography and transesophageal echocardiography. These examinations were performed for recent systemic emboli (15 patients), fever of unknown etiology (11 patients), routine postoperative evaluation (56 patients), and other reasons (32 patients). Based on transthoracic echo diagnosis, all prostheses were considered normal. Yet, in 20 patients transesophageal echocardiography revealed the presence of a 2- to 15-mm-long mobile thrombus localized on the atrial surface of the prosthesis. When compared with the remaining 94 patients with no visible thrombi, there was no significant difference between the two groups in terms of incidence of atrial fibrillation (65% versus 52%), left atrial size (48 +/- 9 versus 51 +/- 13 mm), left ventricular end-diastolic diameter (49 +/- 10 versus 51 +/- 13 mm) and fractional shortening (28 +/- 9% versus 31 +/- 10%), presence of spontaneous contrast to the left atrium (40% versus 41%), transprosthetic mean pressure gradient (4.0 +/- 1.4 versus 3.9 +/- 1.5 mm Hg), or the type of prosthesis used. After we discovered a nonobstructive thrombosis, patients were treated with heparin (n = 9) or oral anticoagulation (n = 11). The presence of a localized thrombus was confirmed in 3 patients who were operated on. In the present study, evolution appeared to depend on thrombus size: of 14 patients exhibiting a small (< 5 mm) thrombus, 10 had an uneventful course, whereas 5 of 6 patients with a large (> or = 5 mm) thrombus developed complications or died. CONCLUSIONS: Transesophageal echocardiography appears to be a reliable method to diagnose thrombi on a mechanical mitral valve prosthesis, even when transthoracic Doppler echocardiographic parameters appear to be normal. Transesophageal echo assessment of thrombus size may be helpful in deciding whether a patient with mitral prosthesis should be treated by anticoagulation, thrombolysis, or valve rereplacement.

Adult

The role of universities and the ethics of their interventions in international health.

Even though exchange has always been a part of the University essence, we are now witnessing an important movement towards internationalization, which cannot be indissoluble from the phenomenon of the globalization of culture and exchanges. In the international health field, universities, either in the South or North, have traditionally played an important role which is ever expanding, due to the broadening of the concept of international health. In Canada, academic centers of international health have developed rapidly over the last decade, along with a network linking all universities that are active in the field. The development of this type of center at the University of Montreal is described in this paper. The lessons learned there lead us to insist on the importance of the attachment of international cooperation development programs to the teaching assignments and research programs of universities, and to pay particular attention to research in order to strive for excellence. It is also important to pay attention to the freedom of thought and action which is a fundamental value among university members. Among the universities involved in international health, some have gone adrift: be it the opportunism of some or the inappropriate use of university expertise by international cooperation agencies of others. Universities, in their undertakings, must respect, in addition to their own traditional ethic, the one of development.

Ethics, Professional

Quality, cost and utilization of health services in developing countries. A longitudinal study in Zaïre.

Many developing countries, particularly in Africa, have recently introduced payment schedules based on the selling of essential drugs. This is one of the main elements of the Bamako Initiative according to which the income generated would ensure a reliable supply of drugs and would improve other aspects of the quality of the services offered. Thus, quality improvements would compensate for the financial barrier and as a result the utilization of public health services would be increased or at least maintained. These hypotheses have proven to be partially valid, since there have been cases where the utilization of health services has increased and others where it has decreased; these inconclusive results have fuelled criticisms concerning the inequitable nature of these measures. This longitudinal study in a rural community of Zaïre shows that the utilization of health services had diminished by close to 40% over 5 yr (1987-1991) and that 18-32% of this decrease is explained by cost. The regular supply of drugs and the improvement in the technical quality of the services--technical qualification of the staff, allocation of microscopes, and renovation of the infrastructures--was not enough to compensate for the additional financial barriers created by the increased cost of services. However, on a local level, the interpersonal qualities displayed by some of the nurses sometimes helped to compensate for the negative effects of the costs, and even to increase the level of utilization of some health centres. The quality of public services has often been neglected in developing countries. While some attention is given to technical qualities, the interpersonal components of the quality of the services are generally ignored or underestimated by planners and they are the very components which are most resistant to change. It will be a major challenge for health systems to address this issue of quality of care in order to minimize the negative impact of the introduction of user payment schemes. Therefore, now is the time to place quality next to coverage in planners' agendas.

Adult

Susceptibility mutations in the mitochondrial small ribosomal RNA gene in aminoglycoside induced deafness.

Aminoglycoside induced deafness has been linked recently to a predisposing homoplasmic mutation in the 3' end of the small ribosomal RNA (rRNA) gene of the human mitochondria (1555 A-->G) that makes the mitochondrial rRNA structurally more similar to its bacterial counterpart. This mitochondrial DNA mutation was consistently found in families in which the susceptibility to develop ototoxic deafness was inherited through the maternal lineage. However, the 1555 A-->G mutation was rarely found in sporadic patients in China, where a significant proportion of the population has been exposed to aminoglycosides. To further characterize the mutations predisposing to aminoglycoside ototoxicity, we analysed the 12S rRNA gene in 35 Chinese sporadic patients without the 1555 A-->G mutation. Using single stranded conformational polymorphism (SSCP) analysis, heteroduplex (HD) analysis, sequencing, and allele specific oligonucleotide hybridization, we found three out of 35 sporadic patients with unique sequence changes in the 12S rRNA gene. Two of the patients had homoplasmic mutations. One patient displayed localized heteroplasmy around nt 961, with an absence of the thymidine at this position and different populations of mitochondrial DNA with varying numbers of inserted cytosines. The description of these putative susceptibility mutations, in particular the heteroplasmic mutation around nt 961, provides further support for the important role of the mitochondrial 12S rRNA in genetic predisposition to aminoglycoside induced ototoxic deafness.

Aminoglycosides

Stimulation of ileal calcium absorption by sorbitol, L-xylose, or creatine via a decrease in luminal sodium concentration: relation with concomitant changes in enterocyte energy metabolism.

Ligated ileal loops, 30 cm in length, of 4-month-old male Wistar rats were instilled with 3 ml of a 10 mM CaCl2 solution (added with 0.25 muCi 45Ca) in the absence (control) or presence of 100mM sorbitol, L-xylose, or creatine. Ileal calcium (Ca) transport, measured by plasma 45Ca appearance, was found to be similar 30 minutes after fluid instillation in all four instances. However, thereafter, 45Ca appearance in plasma did not increase further in control animals whereas it increased twice as much during the subsequent 30 minutes in the presence of sorbitol, L-xylose, or creatine. However, when loops of similar length were instilled with only 1.0 ml of such solutions, the sorbitol effect was already observed during the first 30 minutes. The stimulation of ileal Ca absorption induced by the presence of sorbitol appeared to be due to a cellular effect, associated with a decreased flux across the paracellular pathway, as indicated by 3H-mannitol absorption. The presence of sorbitol in instilled ileal solution induced a significant decrease in luminal Na, K, bicarbonate, and Cl concentrations at each time point studied (30, 60, 120, or 240 minutes after instillation). Thirty minutes after instillation, no difference in soluble Ca concentration was observed between control and experimental rats. After 60 minutes, Ca concentration was dramatically decreased in control rats but it remained nearly constant in experimental animals. Thus, the presence of substances enhancing ileal Ca transport favored the maintenance of soluble Ca in ileal solution during longer time periods than their absence. In the ileal enterocyte, these substances induced a twofold increase of ATP content compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption

[Osteomalacia of renal origin disclosing Gougerot-Sjögren syndrome].

Latent renal tubular diseases are common in Sjögren's syndrome but rarely complicated by osteomalacia. The authors report a 28 years old woman's case where osteomalacia reveal the disease. In the other hand, pseudo-lymphoma is suspected from radiographic features. According to several studies, the authors review different types of renal diseases and describe different physiopathological hypotheses about bone involvement and pseudo-lymphomas.

Acidosis, Renal Tubular

[Contribution of transesophageal echocardiography to the diagnosis of pulmonary embolism].

Between September 1992 and August 1993 transoesophageal echocardiography was undertaken in 30 patients with clinical and scintigraphic signs of pulmonary embolism. The diagnosis was confirmed by pulmonary angiography (1 patient had failure of venous puncture; 1 patient refused the investigation). The aim of this study was to assess the tolerance and to determine the diagnostic value of transoesophageal echocardiography in patients with suspected pulmonary embolism (PE). Two groups of patients were identified: Group 1: presence of thrombus in the pulmonary artery on transoesophageal echocardiography and group 2: absence of visible thrombus. The produce was well tolerated in all patients. In 21 cases (group 1) 21 thrombi were observed in the right pulmonary artery and 4 thrombi in the left pulmonary artery. The appearances were those of a mobile venous thrombosis in 20 cases (91%) and of clearcut amputation of the proximal segment of the right pulmonary artery in 1 case. No thrombus was detected in 9 patients (group 2). In group 1, the first clinical signs occurred 12 +/- 12 days and the latest signs 2 +/- 3 days before the investigation. One patient had a history of chronic bronchitis. Two patients had a history of PE but with no sign of chronic post-embolic cor pulmonale. Twenty patients underwent pulmonary angiography. Miller's index was 71 +/- 9% and obstruction of proximal pulmonary arteries was observed in 20 patients. In group 2, the PE was confirmed at angiography in 8 cases. The first clinical signs dated from 27 +/- 54 days and the latest signs were observed 6 +/- 4 days before investigation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Colocalization of centromeric and replicative functions on autonomously replicating sequences isolated from the yeast Yarrowia lipolytica.

Two sequences (ARS18 and ARS68) displaying autonomous replication activity were previously cloned in the yeast Yarrowia lipolytica. The smallest fragment (1-1.3 kb) required for extrachromosomal replication of a plasmid is significantly larger in Y. lipolytica than in Saccharomyces cerevisiae. Neither autonomously replicating sequence (ARS) is homologous with known ARS or centromere (CEN) consensus sequences. They share short regions of sequence similarity with each other. These ARS fragments also contain Y. lipolytica centromeres: (i) integration of marker genes at the ARS loci results in a CEN-linked segregation of the markers, (ii) an ARS on a plasmid largely maintains sister chromatid attachment in meiosis I, and (iii) integration of these sequences at the LEU2 locus leads to chromosome breakage. Deletions performed on ARS18 show that CEN and ARS functions can be physically separated, but both are needed to establish a replicating plasmid.

Base Sequence

Identical mitochondrial DNA deletion in mother with progressive external ophthalmoplegia and son with Pearson marrow-pancreas syndrome.

We describe a family in which the mother has progressive external ophthalmoplegia with the common 4977 base pair deletion, and her son has a syndrome similar to the Pearson marrow-pancreas syndrome with the identical deletion. This case extends the clinical phenotype of the Pearson syndrome and raises the possibility that developmentally regulated tissue-specific nuclear factors are responsible for the differential phenotypic expression of these two mitochondrial disorders.

Adult

IS870 requires a 5'-CTAG-3' target sequence to generate the stop codon for its large ORF1.

The TB regions of the Agrobacterium vitis octopine/cucumopine Ti plasmids constitute a family of related structures. All contain a bacterial insertion element downstream of the TB-iaaM gene, IS870.1. Whereas 43 isolates with octopine/cucumopine Ti plasmids carry only one IS870 copy, strain Ag57 carries a second copy (IS870.2) 3.9 kb to the right of IS870.1 and part of the same TB region. Two other octopine/cucumopine strains carry an IS870 copy on their chromosome (IS870.3). A study of the unmodified insertion sites of IS870.2 and IS870.3, cloned from closely related strains, enabled us to delimit the IS870 elements. IS870 has a size of 1,152 bp and is terminated by inverted repeats. It contains a large open reading frame without a stop codon. However, a stop codon is generated by insertion into the target sequence 5'-CTAG-3'. IS870 is related to five other insertion sequence elements. For two of these, the stop codon of the largest open reading frame is also created by insertion into a CTAG target site.

Amino Acid Sequence

[Role of ultrasonographic tests in the diagnosis of moderate to severe pulmonary embolism].

Between November 1991 and June 1992, 50 patients suspected of pulmonary embolism (SP > 20%) underwent Doppler echocardiography, venous Doppler ultrasonography and pulmonary angiography. Pulmonary embolism was confirmed by pulmonary angiography in all patients but 3 (2 pts: mean pulmonary pressure > 50 mmHg and 1 pt: mobile thrombus between the infundibulum and the main pulmonary artery). Two groups were identified on the basis of Miller's index: Group 1: "non-massive" pulmonary embolism, Miller < 60% (n = 18); Group 2: "massive" pulmonary embolism, Miller > or = 60% (n = 29). The patient with thrombus in the main pulmonary artery and the two with high pulmonary pressures were included in Group 2. Venous Doppler ultrasonography was performed in 96% (n = 48) of patients, including 90% within the first 24 hours. No distinction could be drawn between the two groups on the basis of venous Doppler ultrasonography findings. A majority of patients had thrombosis of main collecting vessels (Group 1 = 75%, Group 2 = 78%) and 10% of patients had no venous thrombosis of the lower limbs. Doppler echocardiography was performed in all patients, including 94% (n = 47) within the first 24 hours. Dilatation of the left ventricle as well as analysis of septal contraction was evaluable in all patients except one of Group 2, because of poor technical quality and of artificial pacing. A RV/LV ratio > 0.60 was found in 97% (30/31) of patients of Group 2 as compared with 39% (7/18) in Group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

[A new cause of torsades de pointes: combination of terfenadine and troleandomycin].

The authors report a case of wave-burst arrhythmia which occurred during combined treatment with terfenadine and troleandomycin. After the treatment had been stopped and the QT interval returned to normal, terfenadine treatment was reintroduced with no major change in repolarization. However, as soon as troleandomycin was associated, there was a significant and progressive prolongation of QT. Normal repolarization was restored again with troleandomycin alone. These findings suggest drug interaction between terfenadine and troleandomycin. Although it is not possible to carry out serum assays of terfenadine, one possible physiopathological hypothesis would be an overdose of terfenadine. Terfenadine undergoes hepatic oxidative metabolism involving the cytochrome P450 pathway and troleandomycin inhibits cytochrome P450. In the literature, a case has already been described of wave-burst arrhythmia related to terfenadine overdose when associated with a cytochrome P450 inhibitor.

Aged

[Evaluation of a new cardiotonic agent on human isolated atrium].

The action of a phosphodiesterase inhibitor, RGW 29 38, was analysed experimentally. A preliminary study with guinea pig isolated heart, using Langhendorf's method, revealed a cardiotonic effect, though less than with isoprenaline and dobutamine, with which it was compared. The inotropic action of the compound was then studied using human isolated atrium. The model is described. It consisted of measurement by a strain gauge of the contractions obtained in a stimulated atrial fragment obtained during a surgical procedure. The following parameters were analysed, expressed as percentage increase in relation to baseline conditions: maximum tension developed, positive dP/dt and negative dP/dt. The effect of RGW (n = 6) was compared with that of isoprenaline (n = 7). RGW caused an increase in maximum tension of 195% +/- 91%, in positive dp/dt of 110% +/- 72% and in negative dp/dt of 168 +/- 54%. This increase was, however, less than that seen in the isoprenaline group. Thus RGW had a definite positive inotropic effect on guinea pig isolated heart and human isolated atrium, though less than that of the catecholamines with which it was compared. Isolated human atrium appears to be a useful study model, in particular for analysis of the inotropic action of drugs.

Animals