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Biomedical subjects

L Simon

Publications and source records attributed to L Simon.

At least 37 records · Page 2Linked to original sources

Anatomical basis of a common embryological origin for epispadias and bladder or cloacal exstrophies.

Epispadias, bladder exstrophy and its variants are in the first place usually considered as urological anomalies. Embryological theses and therapeutic approaches are mainly based upon this aspect. We challenge this point of view, in order to bring out a new axis of research about this still misknown pathologic field. A review of 16 cases of bladder exstrophy, 6 epispadias cases, and one cloacal exstrophy case, which had never been described before, revealed that the almost constant bony defect of the pelvic ring was linked with the severity of the visceral features, and with the continence status in epispadias cases. The commonly admitted theories about exstrophy development are based on a primary defect of the cloacal membrane. We suggest that the first anomaly could lie in a lack of rotation in the pelvic ring primordia.

Bladder Exstrophy

[Evaluation of hemostasis before obstetrical epidural anesthesia: a survey in 435 French obstetric departments].

OBJECTIVES: To specify by which means French anaesthesiologists evaluate the haemostasis profile of pregnant women before epidural analgesia. STUDY DESIGN: Nationwide retrospective survey. MATERIAL: Questionnaire sent of 847 French obstetrical units. METHODS: Comparison of categorical qualitative parameters using a chi 2 test. RESULTS: Answers from 435 centres, including 1,834 anaesthesiologists, performing 227 x 10(3) epidurals for 411 x 10(3) deliveries/year were obtained. A preanaesthetic clinical assessment was performed systematically in two out of three units, and blood samples for PT, aPTT and platelet count were taken in more than 90% of the centres. These laboratory examinations were often made during the 9th month of pregnancy (74%). For more than one-third of the anaesthesiologists, biological data are not essential before epidural puncture. In addition, the lower limits considered as being safe before epidural puncture were highly variable between the teams. CONCLUSIONS: Coagulation laboratory tests are almost always ordered before epidural obstetrical analgesia in France. The rationale to perform them is not always related to pregnancy induced haemostatic changes. Therefore, this problem should be clarified by a consensus conference for both practical and economical reasons.

Adult

[Agranulocytosis after application of silver sulfadiazine in a 2-month old infant].

BACKGROUND: A granulocytosis associated with the use of silver sulfadiazine has been described in burn patients. This agranulocytosis may be due to either an allergic reaction or a bone marrow toxicity by silver sulfadiazine. CASE REPORT: A 1-month old baby was hospitalized in pediatric intensive care unit after a stage one repair of a tracheoesophegeal fistula. Gastroesophageal reflux and tracheomalacia appeared in the post operative period. When she was 2-months old, she developed a perineal erythema. A topical therapy was begun, with daily applications of silver sulfadiazine and ketoconazole. Five days later, agranulocytosis (granulocytes = 0.21 x 10(9).L-1) occurred. Silver sulfadiazine therapy was immediately stopped. Granulocyte count returned to normal over a few days. No other etiology than silver sulfadiazine could be found to explain agranulocytosis. The small surface of administration, the chronology of the events and the rapid correction of the disorders after silver sulfadiazine interruption argued for an immuno-allergic reaction to this drug. Medical problems were easily controlled and the patient recovered well. CONCLUSION: This event occurred when sulfadiazine was applied in a small cutaneous area in a young baby. This may be an argument for an allergic reaction; alternatively, it could be explained by an increased cutaneous absorption of a cytotoxic drug in younger people.

Agranulocytosis

Effect of solid and liquid diet on uptake of large particulates across intestinal epithelium in rats.

The effect of diet composition on the uptake of particulates across the gastrointestinal epithelium has been examined in fasted male weanling Sprague-Dawley rats by estimating the systemic uptake of orally administered 2-microns latex polystyrene microspheres. Using a tissue solubilization assay, particle transfer in animals maintained on a fluid diet was determined. A larger number of particles was transferred from the gut lumen to the internal organs, including the mesenteric lymph node, spleen, bone marrow, liver, kidney, and heart of animals fed solid pelleted diet than those maintained on a fluid-diet 4 hr after oral administration of particles. The increase in particle number in rats fed the solid diet was only statistically significant (P < 0.05) for brain tissue in the analysis for trend. However, the number of particles retained in the proximal region of the gut at the end of this period was greater in animals fed the fluid diet. This work demonstrates that diet composition is important in gastrointestinal transepithelial translocation of microspheres.

Adolescent

Terror management theory and self-esteem: evidence that increased self-esteem reduces mortality salience effects.

On the basis of the terror management theory proposition that self-esteem provides protection against concerns about mortality, it was hypothesized that self-esteem would reduce the worldview defense produced by mortality salience (MS). The results of Experiments 1 and 2 confirmed this hypothesis by showing that individuals with high self-esteem (manipulated in Experiment 1; dispositional in Experiment 2) did not respond to MS with increased worldview defense, whereas individuals with moderate self-esteem did. The results of Experiment 3 suggested that the effects of the first 2 experiments may have occurred because high self-esteem facilitates the suppression of death constructs following MS.

Analysis of Variance

Terror management and cognitive-experiential self-theory: evidence that terror management occurs in the experiential system.

The authors hypothesized, on the basis of terror management theory and cognitive-experiential self-theory, that participants in an experiential mode of thinking would respond to mortality salience with increased worldview defense and increased accessibility of death-related thoughts, whereas participants in a rational mode would not. Results from 3 studies provided convergent evidence that when participants were in an experiential mode, mortality salience produced the typical worldview defense effect, but when participants were in a rational mode it did not. Study 4 revealed that mortality salience also led to a delayed increase in the accessibility of death-related thoughts only when participants were in an experiential mode. These results supported the notion that worldwide defense is intensified only if individuals are in an experiential mode when considering their mortality. Discussion focuses on implications for understanding terror management processes.

Adaptation, Psychological

Suppression, accessibility of death-related thoughts, and cultural worldview defense: exploring the psychodynamics of terror management.

Previous research has shown that after a mortality-salience (MS) treatment, death thought accessibility and worldview defense are initially low and then increase after a delay, suggesting that a person's initial response to conscious thoughts of mortality is to actively suppress death thoughts. If so, then high cognitive load, by disrupting suppression efforts, should lead to immediate increases in death thought accessibility and cultural worldview defense. Studies 1 and 2 supported this reasoning. Specifically, Study 1 replicated the delayed increase in death accessibility after MS among low cognitive load participants but showed a reversed pattern among participants under high cognitive load. Study 2 showed that, unlike low cognitive load participants, high cognitive load participants exhibited immediate increase in pro-American bias after MS. Study 3 demonstrated that worldview defense in response to MS reduces the delayed increase in death accessibility. Implications of these findings for understanding both terror management processes and psychological defense in general are discussed.

Affect

Pre-anaesthetic assessment of coagulation abnormalities in obstetric patients: usefulness, timing and clinical implications.

The usefulness and optimal timing of laboratory coagulation tests before obstetric extradural analgesia are controversial. Moreover, the significance of mild coagulation abnormalities during pregnancy remains unclear. We have assessed the reliability of coagulation tests performed several weeks before delivery as predictors of coagulation abnormalities during labour. Platelet count, plasma fibrinogen concentration, prothrombin time (PT) and activated partial thromboplastin time (aPTT) were sampled in 797 women during the ninth month of pregnancy and checked during labour. Platelet count was less than 100 x 10(9) litre-1 for 11 women during labour. Only three had been detected by the first sample. Platelet count less than 100 x 10(9) litre-1 or fibrinogen concentration less than 2.9 g litre-1 during labour were associated with an increase in the incidence of postpartum haemorrhage (odds ratio = 19.7). We conclude that a platelet count several weeks before delivery was not reliable in predicting thrombocytopenia during labour and that women with mild coagulation abnormalities in early labour may need special attention regarding the risk of postpartum haemorrhage.

Adult

Progression into the first meiotic division is sensitive to histone H2A-H2B dimer concentration in Saccharomyces cerevisiae.

The yeast Saccharomyces cerevisiae contains two genes for histone H2A and two for histone H2B located in two divergently transcribed gene pairs: HTA1-HTB1 and HTA2-HTB2. Diploid strains lacking HTA1-HTB1 (hta1-htb1 delta/hta1-htb1 delta, HTA2-HTB2/HTA2-HTB2) grow vegetatively, but will not sporulate. This sporulation phenotype results from a partial depletion of H2A-H2B dimers. Since the expression patterns of HTA1-HTB1 and HTA2-HTB2 are similar in mitosis and meiosis, the sporulation pathway is therefore more sensitive than the mitotic cycle to depletion of H2A-H2B dimers. After completing premeiotic DNA replication, commitment to meiotic recombination, and chiasma resolution, the hta1-htb1 delta/hta1-htb1 delta, HTA2-HTB2/HTA2-HTB2 mutant arrests before the first meiotic division. The arrest is not due to any obvious disruptions in spindle pole bodies or microtubules. The meiotic block is not bypassed in backgrounds homozygous for spo13, rad50 delta, or rad9 delta mutations, but is bypassed in the presence of hydroxyurea, a drug known to inhibit DNA chain elongation. We hypothesize that the deposition of H2A-H2B dimers in the mutant is unable to keep pace with the replication fork, thereby leading to a disruption in chromosome structure that interferes with the meiotic divisions.

Histones

Pathogen-induced programmed cell death in tobacco.

Sacrificing an infected cell or cells in order to prevent systemic spread of a pathogen appears to be a conserved strategy in both plants and animals. We studied some of the morphological and biochemical events that accompany programmed cell death during the hypersensitive response of tobacco plants infected with tobacco mosaic virus. Certain aspects of this cell death process appeared to be similar to those that take place during apoptosis in animal cells. These included condensation and vacuolization of the cytoplasm and cleavage of nuclear DNA to 50 kb fragments. In contrast, internucleosomal fragmentation, condensation of chromatin at the nuclear periphery and apoptotic bodies were not observed in tobacco plants during tobacco mosaic virus-induced hypersensitive response. A unique aspect of programmed cell death during the hypersensitive response of tobacco to tobacco mosaic virus involved an increase in the amount of monomeric chloroplast DNA. Morphological changes to the chloroplast and cytosol of tobacco cells and increase in monomeric chloroplast DNA occurred prior to gross changes in nuclear morphology and significant chromatin cleavage. Our findings suggest that certain aspects of programmed cell death may have been conserved during the evolution of plants and animals.

Apoptosis

Incidence of childhood-onset IDDM in black African-heritage populations in the Caribbean. The Caribbean African Heritage IDDM Study (CAHIS) Group.

OBJECTIVE: To compare incidence rates of childhood-onset IDDM among black African-heritage populations age 0-19 years in the Caribbean region. RESEARCH DESIGN AND METHODS: Population-based registries for IDDM were established on the eastern Caribbean islands of Antigua, Barbados, Dominica, St. Croix, St. Kitts, St. Thomas, and Tortola using standardized criteria from the World Health Organization (WHO) Multinational Project for Childhood Diabetes (DiaMond). Average annual incidence rates (IR) with 95% CI for 0-19 years olds were computed using the DiaMond Registry program for the 5-year period from 1989 to 1993. Poisson regression analysis was used to determine differences in incidence rates. RESULTS: The highest incidence rate for 0-19 year olds was for the black African-heritage population of St. Croix (IR 10.09 per 100,000; 95% CI 4.35-19.89), one of the U.S. Caribbean islands. A significant (P < 0.05) 3.9 variation in IDDM incidence across the registries was found when the IR for St. Croix was compared to the IR for Barbados (IR 2.57 per 100,000; 95% CI 0.90-4.64). CONCLUSIONS: The variation in childhood-onset IDDM incidence rates among the black populations of the eastern Caribbean islands is consistent with the geographic variation in IDDM incidence seen among African Americans in the U.S. Variation in incidence rates of childhood diabetes in black populations may reflect differences in level of white genetic admixture or exposure to environmental diabetogenic agents.

Adolescent

Ebrotidine versus ranitidine in the healing and prevention of relapse of duodenal ulcer. A multicentre, double-blind, parallel, randomized, controlled study.

Two hundred and fifty patients were included in a double-blind, parallel, randomized, controlled clinical trial. Duodenal ulcer treatment lasted up to 8 weeks. Forty-nine patients were followed up for prevention of ulcer relapse for up to one year. All patients received either ranitidine (300 mg/day in the healing phase and 150 mg/day in the follow-up phase) or ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4 -thiazolyl]methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide , CAS 100981-43-9, FI-3542) (400 mg/day in both phases) as a single dose at bedtime. Both groups were matched in all demographic parameters, except for a significantly higher percentage of smokers in the ranitidine group. The percentage of total healing was almost the same with both products. Healing occurred in a higher percentage with ebrotidine at weeks 4 (75% versus 66.7%) and 6 (87% versus 79.7%). A higher effect of ebrotidine on the incidence of duodenitis was identified during the whole study, but only reached statistical significance at week 6. The relapse rate during the follow-up phase showed no differences between the two study treatments, relapse percentage figures being 25% for ebrotidine and 24% for ranitidine. There were no differences in the number of unscheduled visits between the two groups, although 57% of patients in the ranitidine group had to make a second follow-up visit, as compared with 33% in the ebrotidine group. Both drugs caused hardly any side effects, affecting only one patient from each group: one patient with ebrotidine suffered from diarrhoea and one patient with ranitidine developed a skin rash on the limbs. Administration of ebrotidine in a single dose (400 mg/d) was at least as effective and safe as ranitidine both for healing and relapse prevention in patients with duodenal ulcer.

Adult

[Surgical approach on rabbit embryos. A model trial of bladder exstrophy].

We describe herein a new model of surgical approach of an early mammalian embryo. Indeed the developmental mechanisms of numerous congenital anomalies, such as bladder exstrophy, remain obscure, and progresses in their knowledge must be achieved to propose better treatments. But up to now all the successful reports in experimental models of early produced malformations concerned birds or batracians, whose development is very different from human. We used the rabbit. Twenty-five time matted does were operated at 12.5 days of gestation. Out of their 247 embryos, 99 underwent a surgical procedure. Forty-eight were injured in order to produce an exstrophy. In 18 cases, the embryo extruded from the uterine cavity and could not be reintegrated, and 2 sacs were found empty. The remaining 31 were only exteriorized. Nine additional does received intravenous teratogen at 12.5 days of gestation. In the group of operated embryos we obtained 6 full-term fetuses, one of whom had a cloacal exstrophy. No exstrophy was noted among the intact embryos, neither in the 87 fetuses submitted to the teratogen. We conclude that: it is possible to operate on an early mammalian embryo, and to obtain further growth until term and that the exstrophy we observed in one case resulted from the surgical specific procedure.

Animals

Betidamino acids: versatile and constrained scaffolds for drug discovery.

Betidamino acids (a contraction of "beta" position and "amide") are N'-monoacylated (optionally, N'-monoacylated and N-mono- or N,N'-dialkylated) aminoglycine derivatives in which each N'acyl/alkyl group may mimic naturally occurring amino acid side chains or introduce novel functionalities. Betidamino acids are most conveniently generated on solid supports used for the synthesis of peptides by selective acylation of one of the two amino functions of orthogonally protected aminoglycine(s) to generate the side chain either prior to or after the elongation of the main chain. We have used unresolved Nalpha-tert-butyloxycarbonyl-N'alpha-fluorenylmethoxycarbonyl++ + aminoglycine, and Nalpha-(Nalpha-methyl)-tert-butyloxycarbonyl-N'alpha-fluo renylmethoxycarbonyl aminoglycine as the templates for the introduction of betidamino acids in Acyline [Ac-D2Nal-D4Cpa-D3Pal-Ser-4Aph(Ac)-D4Aph(A c)-Leu-Ilys-Pro-DAla-NH2, where 2Nal is 2-naphthylalanine, 4Cpa is 4-chlorophenylalanine, 3Pal is 3-pyridylalanine, Aph is 4-aminophenylalanine, and Ilys is Nepsilon-isopropyllysine], a potent gonadotropin-releasing hormone antagonist, in order to test biocompatibility of these derivatives. Diasteremneric peptides could be separated in most cases by reverse-phase HPLC. Biological results indicated small differences in relative potencies (<5-fold) between the D and L nonalkylated betidamino acid-containing Acyline derivatives. Importantly, most betide diastereomers were equipotent with Acyline. In an attempt to correlate structure and observed potency, Ramachandran-type plots were calculated for a series of betidamino acids and their methylated homologs. According to these calculations, betidamino acids have access to a more limited and distinct number of conformational states (including those associated with alpha-helices, beta-sheets, or turn structures), with deeper minima than those observed for natural amino acids.

Amino Acid Sequence

Amyloidosis-related cauda equina compression in long-term hemodialysis patients. Three case reports.

STUDY DESIGN: These case reports illustrate the neurologic manifestations due to beta 2 microglobulin amyloid deposition at the lumbar spine level in long-term hemodialysis patients. OBJECTIVE: Radiologic investigations suggested the amyloid origin of extradural soft tissue deposition, which was confirmed by histologic examination after surgical excision. SUMMARY OF BACKGROUND DATA: Although cervical myelopathy is a recently recognized complication of long-term dialysis-related beta 2 microglobulin amyloidosis, neurologic manifestations due to amyloid deposition at the lumbar spine level have rarely been reported. METHODS: Three case reports of cauda equina compression in long-term hemodialysis patients are presented. Follow-up radiography, computed tomography, and magnetic resonance imaging were performed and patients underwent surgical decompression of the thecal sac. RESULTS: In two patients, the compression resulted from the development of a destructive spondylarthropathy, and from the infiltration of extradural spaces and ligaments by an abnormal soft tissue. The third patient had lumbar spinal stenosis due to multiple disc protrusion and to hypertrophy of facet joints and ligamentum flavum. Multilevel laminectomies enabled excision of an abnormal fibrous tissue responsible for the thecal sac compression. Histologic examination of the excised fibrous tissues disclosed amyloid deposits in intervertebral discs, apophysial joints, and ligaments. CONCLUSIONS: In long-term hemodialysis patients, cauda equina compression may develop as the consequence of beta 2 microglobulin amyloid deposition in lumbar intervertebral discs, facet joints, and ligaments. Magnetic resonance imaging is well suited to show the extent of the compression and supports the argument for the amyloid origin of extradural soft tissue.

Adult