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Biomedical subjects

G Dumas

Publications and source records attributed to G Dumas.

At least 37 records · Page 2Linked to original sources

[Semiologic value and optimum stimuli trial during the vibratory test: results of a 3D analysis of nystagmus].

Nystagmus signaling vestibular dysfunction was observed after vibratory stimulation with a 100 Hz ABC stimulator in a population of 36 patients with unilateral labyrinthine pathology (ULP) (pre and postoperative neuromas, vestibular neurectomies) and 10 patients with vestibular neuritis. The stimulus was applied on 3 bony points of the skull (vertex and 2 mastoids) and 2 muscular points of the neck (right and left posterior cervical region). These results were compared with those in 95 normal subjects and 19 cases of central disease and were correlated on the same day with results of the caloric test and head shaking test (HST). A consistent nystagmus was found in only 6 % of the normal subjects (specificity 94 %) and in 10 % of the central lesions, but in 94 % of the 36 peripheral ULP. The sensitivity of the test was equivalent to the HST. The signal was optimized in 30 patients: stimulus frequency, amplitude, stimulator mass, form of the contact, patient tolerance. The best results were obtained for a frequency of 100 Hz and an amplitude of 0.5 mm (there was no response under 0.1 mm vibration amplitude). Under videoscopy and 3D videonystagmography, the direction or side of the nystagmus was constant, but its axis (horizontal, oblique or rotational) changed according to the location of the stimulator: on the mastoid (elective location of stimulation with responses in 94 % of cases) the axis was most often horizontal or horizontal rotational. On the vertex location (where nystagmus was observed in 60 % of cases) the axis of nystagmus was most often rotational or oblique and sometimes horizontal-rotational. The nystagmus showed short latency (less than 200 ms). It started and stopped as stimulation was initiated and interrupted. Nystagmus persisted for the duration of patient tolerance. This nystagmus generally signifies unilateral vestibular weakness rather than vestibular predominance. It is a good indicator of unilateral vestibular dysfunction and could serve as a useful test in clinical practice. We discuss the origin of the nystagmus which may originate in muscle proprioception (by propagation of the vibration to neck muscles) or in the labyrinth (simultaneous excitation of 3 canals on each side).

Adult↗

VH gene usage by family members affected with chronic lymphocytic leukaemia.

The excess risk of chronic lymphocytic leukaemia (CLL) in the first-degree relatives of affected patients suggests that familial CLL might constitute a useful model to study the pathogenesis of this disease, as has been demonstrated in numerous other neoplastic disorders. Previous studies have shown non-random utilization of immunoglobulin genes in CLL, some germline in sequence and others containing numerous somatic mutations. To investigate whether familial cases of CLL exhibit similarities in the composition of the B-cell receptor repertoire to the pattern expressed by CLL patients as a whole, we have studied 25 CLL patients belonging to 12 different families (four French and eight Italian), each of which contained at least two affected members. Among familial cases, VH gene segment utilization proved non-random and diverged from the frequencies previously reported among unrelated patients with CLL. Specifically, although the 4-34 and 5-51 gene segments were found repeatedly, the 1-69 and 4-39 gene segments were used sparingly and the 3-23 gene segment presented with increased frequency. Following the pattern detected in studies of unrelated patients, the single 1-69 expressing CLL contained an unmutated H chain sequence and included a long HCDR3 interval. In contrast, 3-23 containing H chains all used JH4, retained at most 93% homology with germline sequence, and included only short HCDR3 intervals. The vast majority of the CLL variable domains contained a high degree of somatic mutation and exhibited an excess of replacement mutations in the CDR intervals. These findings suggest that familial CLL cases may preferentially derive from B-cell progenitors that have responded to antigen.

Adult↗

[Gadolinium and contrast medium MRI of the acoustic nerve in patients with meningeal neuritis and acoustico-facial syndrome].

Twelve cases of vestibular neuritis were investigated in gradient echo MRI with gadolinium. Only 3 severe cases associated with an acoustico facial syndrome (2 cases of herpes zoster oticus and one case after influenzae) demonstrated focal enhancement within the internal auditory canal on post contrast T1 weighted images. This enhancement involved at least 2 differents nerves. These 3 severe cases associating sensory neural hearing loss and facial palsy revealed a meningeal reaction after cerebrospinal fluid examination. The enhancement lasted a long time (up to 10 months) in one case of RAMSAY HUNT syndrome associated with a chronic lymphocytic leukemia. The MRI was able to confirm the anatomical reality of the vestibular neuritis and more precisely of the meningoneuritis and gave arguments for the theory of the polyneuropathy of Adour. Enhancement at MRI seems correlated with the severity of the affection (permanent vestibular areflexia in 3 cases and permanent hearing loss in 1 case).

Adult↗

Benign positioning vertigo (BPV) and three-dimensional (3-D) eye movement analysis.

Fifty two patients with positioning nystagmus were studied with the V.N.G. three-dimentional device of ULMER. In benign paroxysmal positional vertigo (BPPV) the torsionnal component is not pure: a vertical and a less important horizontal components also exist. They are not of the same amplitude on both eyes. The torsionnal and horizontal components are more important on the eye ipsilateral to the BPPV. The vertical component is more important on the contralateral eye. The horizontal canal B.P.V. (2% of the cases of B.P.V.) is so defined by the absence of vertical and torsionnal components. Three-D Eye Movement Analysis is helpful for differential diagnosis with the positional protocol described. The characteristics of central and peripheral paroxysmal positional nystagmus are given. The head Tilt and the ocular counter rolling reflex (O.C.R.) can be quantified with this device. It will be useful in the future to better explore the inferior root of the eighth nerve and the otolith organ. For clarity we propose to describe the torsionnal nystagmus so that the results are expressed with respect to the patient: clockwise nystagmus (in reference to the patient) would thus be also right rotatory nystagmus while left rotatory nystagmus would be also anticlockwise.

Adult↗

[Epidemiology of sinusitis seen in hospitalized patients. Apropos of 77 episodes of sinusitis among 72 patients between 1993 and 1996].

The 77 cases of sinusitis seen in 72 patients admitted to the Briançon Hospital between January 1, 1993, and June 30, 1996, were studied. One or both maxillary sinuses were involved in 96.8% of cases. Sinus aspiration was done in 95 cases. All aspirates were subjected to microbiological studies. Of the 45 aspirates that yielded positive cultures, 36 grew one or more pathogenic organisms. The most commonly isolated bacteria were Pseudomonas aeruginosa (n = 7), Streptococcus pneumoniae (n = 5), and Haemophilus influenzae (n = 5). Nosocomial sinusitis defined on a set of criteria including hospital stay duration at onset and an acute tempo of evolution contributed 32.5% of cases overall, 55.2% in the intensive care unit and 18.7% in all other departments combined. Nosocomial cases in the intensive care unit were associated with well-known risk factors, namely tracheal intubation with ventilation and presence of a nasogastric tube. Other study criteria included the type of organism recovered by culture and whether patients ventilated via a tracheal tube had the same organism in their sinus and tracheal tube aspirates. Some nonintensive care patients had none of the known risk factors for sinusitis; prompt diagnosis and treatment of these cases of sinusitis is important to avoid infectious complications, which are, however, less common than in intensive care patients.

Adolescent↗

A murine model of human cold agglutinin disease.

Progress has been limited in the treatment of cold agglutinin (CA) disease by the absence of an animal model. We have recently studied at the molecular level one CA displaying the rare anti-Sia-1b specificity (CAGAS), CAGAS displays strong CA activity and is able to haemolyse mouse RBC in the presence of complement, thus constituting a suitable Ab for creating a murine model of CA disease. In the present work we introduced CAGAS VH and VL domains into eukaryotic expression vectors and transfected them into the non-secreting mouse myeloma X63 cell line. Clones expressing complete engineered pentameric IgM kappa CAGAS (eCAGAS) recapitulating the characteristics of serum CA (sCAGAS) could be obtained. The i.p. injection of eCAGAS to normal BALB/c mice induced a typical haemolytic anaemia, as demonstrated by the presence of spontaneous cold agglutination of RBC, induction of anaemia and significant reticulocytosis. Of interest, conspicuous bilateral ear loss was observed in one of these animals. In addition, i.p. injection of X63 transfected line into BALB/c nude mice induced ascites, typical haemolytic anaemia, and shortening of the mean RBC survival. These findings validate the practical interest of constructing a transgenic mouse model expressing eCAGAS.

Anemia, Hemolytic, Autoimmune↗

Obtaining a functional recombinant anti-rhesus (D) antibody using the baculovirus-insect cell expression system.

The cloning and production of a human anti-rhesus (Rh) D monoclonal antibody (mAb) using the baculovirus-insect cell expression system is described. This monoclonal recombinant antibody R.D7C2 derived from a human parental IgM lambda immunoglobulin was obtained after immortalization of lymphocytes by Epstein-Barr virus (EBV). The human heavy (VH) and light (VL) variable regions were cloned from the parental cell line and genetically fused to the human constant IgG1 heavy (H) and light (L) chain genes (gamma 1 and lambda, respectively). A recombinant baculovirus was constructed that directs the co-expression of genes encoding both genetically fused heavy and light chains under the control of two late and strong baculovirus promoters. After infecting the Spodoptera frugiperda (Sf9) insect cell line with this baculovector, a complete IgG1 mAb was secreted in the culture medium indicating that each immunoglobulin chain was correctly processed and assembled with a functional glycosylation into a tetrameric form. In vitro analysis showed that the functional properties of R.D7C2 using agglutination tests were efficient for the specific recognition of Rh-D-positive red blood cells (RBC). In addition, R.D7C2 showed effector functions of the gamma 1 heavy chain resulting in the lysis of Rh+ papain RBC by an antibody-directed cellular cytotoxicity mechanism. These results demonstrate that R.D7C2 can be produced in the baculovirus-insect cell expression system as a source for potential therapeutic application in the treatment of the haemolytic disease of the newborn.

Animals↗

[Rotatory impulse test does not replace caloric tests].

We sought to determine whether the rotatory impulsional test was capable of exploring the canalar function with sufficient precision to replace the caloric test, as it has been recently affirmed. We first compared the observed preponderance from this test with that measured during a sinusoidal (20 and 4 s) test. We observed that, in the case of a significant preponderance for a given test, there was complete redondance with the preponderance observed with any other test. The rotatory impulsional test does not present any specific advantage compared to other kinetic test as far as the observation of the preponderance phenomenon. We then compared the preponderance with the results of the caloric tests and came to the following conclusions i) the absence of preponderance does not allow us to predict the absence of vestibular deficit, due to the fact that 37% of the deficits were compensated for including acoustic neuroma; ii) the presence of a preponderance does not allow a priori to say whether it is of vestibular, cervical, or central origin and systematic caloric tests shows that almost one fourth of preponderance observed is not associated with unilateral weakness iii) supposing that a clinical argument allow us to conclude as to the probable vestibular origin of a vestibular preponderance, the direction of this preponderance does not allow us to determine which side is involved. In fact, if the undercompensated deficits are 3 times more frequent than overcompensated deficits, the proportion of preponderance not linked to a significant deficit indicates that the probability of encountering a preponderance related to a specific undercompensated deficit is approximately 50%. We thus did not find in the rotatory impulsional test any specific advantage allowing us to predict the laterality of a vestibular lesion.

Caloric Tests↗

[Women and the practice of health in the "Register of counsels' speeches in the Parlement of Paris, 1346-1427"].

The study of women in medieval medical practice is a recent area of research plagued by method, sources, and interpretation problems. The main obstacle is probably the paucity of the documentation, the underrepresentation of women in the sources. Studying the judiciary sources of fourteenth- and fifteenth-century Paris reveals women tried by the highest court of justice in France for illicit practice of medicine. Of 34 trials pertaining to health in the "Registre des plaidoiries du Parlement de Paris 1364-1427," eight cases involve women. Two of these trials are particularly instructive because they give many details on certain aspects of women's practice in the Middle Ages. Perette la Pétone is brought to justice by the "corporation des chirurgiens de Paris" for illicit practice of surgery and Jeanne Pouquelin is tried by the "communauté des barbiers de la ville de Paris" for illicit practice of "barbery." This article includes a transcript of the unpublished sources used for the study of these two cases. They shed some light on questions such as: What is the place and role of women in the medical guilds? How do they acquire the expertise required for these crafts? How are they perceived by their peers and society in general? And what is the extent of their medical knowledge?

France↗

Evidence for an antigen-driven selection process in human autoantibodies against acetylcholine receptor.

Autoantibodies to the nicotinic acetylcholine receptor (AChR) play a central role in the neurological symptoms associated with myasthenia gravis (MG). A better knowledge of the structural organization and of the mechanisms leading to the production of these antibodies may help in understanding the pathogenesis of the disease. To achieve this, four IgG anti-AChR monoclonal autoantibodies obtained in a previous work were derived from lymphoid cells of MG patients. Two of them (MH1 and MH6) were capable of modulating in vitro the expression of AChR at the surface of TE-671 cells. We report here the complete nucleotide sequence of the heavy and light chains of these four antibodies. Although it is difficult to address the issue of VH gene usage in anti-AChR autoantibodies because of the limited number of clones studied, our results associated with others which have appeared in the literature point to non-stochastic usage by anti-AChR antibody of some defined VH genes belonging to VH2 and VH5 minifamilies overexpressed in the fetal repertoire. The second and major aim of this work was to assess the role of an antigen-driven selection process in the production of anti-AChR autoantibodies. When comparing the expressed sequences to their closest germline counterparts, it appeared that all four studied clones displayed numerous mutations in VH regions. In particular, MH1 and MH6, characterized by their AChR modulating capacity, displayed a higher than expected number of mutations and replacements occurring in CDR regions. These data point to an antigen-driven selection process. On the contrary, the mutational process observed in the MH% clone was borderline and that of MH7 was compatible with a random process. Interestingly, when comparing mutations in heavy and light chains, a significantly lower number of mutations were expressed in light chains for the four clones.

Amino Acid Sequence↗

[Benign paroxysmal positional vertigo. Apropos of 51 cases].

51 cases of benign paroxysmal vertigo have been investigated in 3 years. The findings put in evidence: the particular frequency of this pathology (18% of BPPV in a vestibulometry consultation), its opportunist character and the possible association with other more severe pathologies (meningiomas, multiple sclerosis, cerebellar venous angioma, vascular cerebral infarction) or more benign pathologies (labyrinth malformation, middle fossa atrophia). Sémont liberatory maneuver revealed to be much efficient (50% of patients free of disease after a single repositioning manoeuvre). Only 3 cases remaining unchanged after 2 years and intractable were proposed for surgery. We mention 7% of bilateral forms and 5% of alternating recurrent forms (sometimes on the right and sometimes on the left side). The recurrence is noted in 50% of BPPV followed at least during one year. We describe a particular topographic form concerning probably a cupulolithiasis of the external canal. 53% of cases beneficiated of CT-scan or of magnetic resonance imaging. The frequency and the possibility of pathological associations with BPPV bring to a particular vigilance for the diagnosis and to a particular care in the affirmation of the benignity in the case of long lasting vertigo (superior to 6 months), or when the nystagmus duration in Hallpike position is superior to 60 seconds.

Adult↗

V gene usage by seven hybrids derived from CD5+ B-cell chronic lymphocytic leukemia and displaying autoantibody activity.

We report here the complete heavy and light chain variable region sequences of seven heterohybridomas derived from CD5+ chronic lymphocytic leukemia (CLL) B lymphocytes and displaying natural autoantibody activity. The three hybrids displaying a polyreactive pattern of binding used VH4 family members, ie, the VH4-18 gene in germinal configuration in two cases and a VH4 gene with 90% homology with VH4-21 for the third one. A hybrid expressing anti-Sm activity used a VH3 family member with 95.26% homology with the 30P1 gene. The three hybrids exclusively displaying rheumatoid factor activity expressed VH1 family genes: 51P1 gene for two (in germinal configuration in one, and with 93.2% homology in the other), whereas the third one used the V1-3b gene (98.8% homology). Definitive homology with known germline D segments was found for four of the seven hybrids (DN2 in 3 and DLR4 in 1) and JH use appeared to be random. The three hybrids displaying polyreactive activity expressed V kappa I, V lambda III, and V lambda II genes, all in germinal configuration. Among the three hybrids with rheumatoid factor activity, two used the same V kappa II gene with, respectively, 98% and 96% homology with a gene previously described; the third used a V lambda I gene in germinal configuration. Finally, the clone with anti-Sm activity used a V lambda III gene having 97% homology with a germinal gene. Overall, these results attempt to establish the relationship between frequent self-reactivity observed in CD5+ B-CLL and V gene usage. For VH genes, they confirm overexpression of the 51P1 gene in B-CLL and suggest nonstochastic use of two VH4 genes (4-21 and 4-18). For VL genes, available information is too scarce to lead to firm conclusions.

Amino Acid Sequence↗

Effects of Pasteurella multocida toxin on the osteoclast population of the rat.

Pasteurella multocida type D toxin is a peptide shown to induce severe atrophic rhinitis in the pig as the result of an increased osteoclastic resorption of the ventral nasal turbinates. In the present study, the effects of the toxin on the histological, cytochemical and ultrastructural features of the osteoclast population of the rat were examined. Pasteurella multocida toxin induced atrophy of the ventral and dorsal nasal turbinates and thinning of the nasal bones. The number and size of the long bone metaphyseal osteoclasts were significantly increased, but not the number of nuclei per cell. Osteoclasts of toxin-treated rats had more developed clear zones and ruffled borders than those of the controls and their cytoplasmic vacuoles were more abundant and larger. We concluded that P. multocida toxin stimulates bone resorption by osteoclasts in the rat by increasing resorption activity and by increasing their number. Its action is not limited to the nasal turbinates but occurs also in the other bones, such as the long bones.

Acid Phosphatase↗

Serum osteocalcin concentration in horses treated with triamcinolone acetonide.

The effect of triamcinolone acetonide (0.09 mg/kg of body weight, IM) on serum osteocalcin concentration was studied. Two groups of horses were investigated and included clinically normal horses (group 1, n = 5) and horses with chronic obstructive pulmonary disease (group 2, n = 5). Before treatment, results of a t-test did not reveal any significant difference in serum osteocalcin concentration between the 2 groups. After treatment, a significant (P < 0.05) decrease in serum osteocalcin concentration was observed for both groups. Osteocalcin concentration in individual horses reached a minimum by 24 to 48 hours after treatment. In both groups of horses, serum osteocalcin response to glucocorticoid administration was similar. In 7 of 10 horses, return to pretreatment values was observed after 28 days. Pretreatment values for the other 3 horses were reached between 62 and 150 days.

Animals↗

Sex does not influence serum osteocalcin levels in standardbred horses of different ages.

The influence of sex on serum osteocalcin levels was studied in 99 Standardbred horses, 52 males and 47 females. The age varied between the day of birth and five years old. A significant inverse correlation (r = -0.87, p < 0.01) was observed between serum osteocalcin level and the age of the animal. Sex did not influence serum osteocalcin level (p > 0.05). When the subjects were divided into five age groups of six months or less, 6 to 18, 18 to 24, 24 to 36 and between 36 and 60 months, no significant influence of sex was noted. A predictive model for serum osteocalcin levels (y = 52.19 - 0.026 age in days, r2 = 0.76) for Standardbred horses aged between the day of birth and five years is described.

Aging↗

T cell response to myelin basic protein epitopes in multiple sclerosis patients and healthy subjects.

T cell lines and clones specific for human myelin basic protein (BP) were selected from three multiple sclerosis (MS) patients and two healthy subjects and tested for their proliferative responses to a battery of synthetic peptides, 9 to 21 amino acid residues long. The combined amino acid sequence of the peptides spanned the complete sequence of the human BP. The results suggest the development of T cells sensitized to at least four independent regions of the human BP, indicating some diversity of the human T cell repertoire to BP. However, an immunodominant T cell epitope was located in the C-terminal region, defined by residues 149-162. This epitope was recognized by T cells from three subjects out of five (one MS patient and both healthy controls) in the context of different DR specificities. Another epitope (located in the 57-75 region) which triggered one MS patient's T cell response was also recognized by a mycobacteria-specific T cell clone cross-reacting with BP.

Epitopes↗