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Biomedical subjects

F Caron

Publications and source records attributed to F Caron.

At least 37 records · Page 2Linked to original sources

Functional assessment of human femoral arteries after cryopreservation.

PURPOSE: An established method of cryostorage that might preserve the vascular and endothelial responses of human femoral arteries (HFAs) to be transplanted as allografts was studied. METHODS: HFAs were harvested from multiorgan donors and stored at 4 degrees C in Belzer solution before cryostorage. One hundred eleven HFA rings were isolated and randomly assigned to 1 control group of unfrozen HFAs and 2 groups of HFAs cryopreserved for 7 and 30 days, respectively. Cryopreservation was performed in Elohes solution containing dimethyl sulfoxide (1.8 mmol/L), and the rate of cooling was 1.6 degrees C/min, until -141 degrees C was reached. The contractile and relaxant responses of unfrozen and frozen/thawed arteries were assessed in organ bath by measurement of isometric force generated by the HFAs. RESULTS: After thawing, the maximal contractile responses to all the contracting agonists tested (KCl, U46619 [a thromboxane A2-mimetic], norepinephrine, serotonin, and endothelin-1) were in the range of 7% to 34% of the responses in unfrozen HFAs. The endothelium-independent relaxant responses to forskolin and verapamil were weakly altered, whereas the endothelium-independent relaxant responses to sodium nitroprusside were markedly reduced. Cryostorage of HFAs also resulted in a loss of the endothelium-dependent relaxant response to acetylcholine. The vascular and endothelial responses were similarly altered in the HFAs cryopreserved for 7 and 30 days. CONCLUSION: The cryopreservation method used provided a limited preservation of HFAs contractility, a good preservation of the endothelium-independent relaxant responses, but no apparent preservation of the endothelium-dependent relaxation. It is possible that further refinements of the cryopreservation protocol, such as a slower rate of cooling and a more controlled stepwise addition of dimethyl sulfoxide, might allow better post-thaw functional recovery of HFAs.

Cryopreservation↗

Effect of a single oral dose of two erythromycin ethylsuccinate formulations on gastric emptying in healthy volunteers: a scintigraphic study.

Macrolides are potential gastrokinetic agents. The purpose of this study was to assess the effect of a single oral dose of two erythromycin formulations on gastric emptying of the solid and liquid phases in twelve healthy volunteers and to seek a correlation between pharmacokinetic parameters and changes in gastric emptying. The gastric emptying times of liquids and solids were measured simultaneously by means of a scintigraphic technique after a single oral administration of amorphous erythromycin ethylsuccinate (500 mg), crystalline erythromycin ethylsuccinate (1000 mg) or a placebo, in a double-blind crossover study in three separate weeks. Blood samples were obtained for erythromycin assay. The two oral formulations induced a similar acceleration of gastric emptying. When compared to the placebo, both erythromycin preparations significantly shortened the gastric transit time of solids and liquids (respectively 30% and 20% on average, p < 0.01). The incidence of gastrointestinal side-effects was similar with the two erythromycin forms and the placebo. No correlation was found between the peak serum erythromycin concentrations and the solid or liquid gastric half-lives. With the amorphous formulation, the area under the plasma time-concentration curves was small and solid and liquid gastric emptying were strongly accelerated, pointing to a direct effect on the gastrointestinal smooth muscle.

Administration, Oral↗

Acute Q fever pneumonia: a review of 80 hospitalized patients.

STUDY OBJECTIVES: To emphasize epidemiologic, clinical, or radiologic characteristics whose detection could lead to an early diagnosis and to enhance therapeutic efficacy. PATIENTS: Eighty hospitalized patients from 1982 to 1996. DESIGN: The diagnosis of Q fever infection was serologically confirmed in all the patients (phase II Coxiella burnetii antibody) using the complement fixation test and/or the indirect immunofluorescence antibody test. RESULTS: Patients from rural and urban areas were noted in the same proportion; however, the usual epidemiologic factors such as contact with cats or farm animals were found in 40% of the patients. Mean age+/-SD was 49+/-20 years, and there was a higher sex ratio of male to female patients (1:3.44). We found a specific seasonal distribution since 80% of the cases occurred between February and May. Delay before referring to hospital was 8.2+/-7.8 days, while 69.3% of the patients received an antibiotic treatment that was mainly penicillin or cephalosporin. The dominant clinical features were dry cough and high fever, as the maximal temperature reached more then 40 degrees C in 58% of the patients. Digestive symptoms were rare. WBC count remained within normal range in 80% of the cases with a low proportion of lymphocytes in half of the patients, and the sedimentation rate was usually elevated (55+/-34 mm). Altered liver function consisted more frequently in an elevated level of alkaline phosphatase (70% of the cases) than transaminases, while hyponatremia was frequently mentioned (28.2% of the patients). We found radiologic evidence of unique lobar or segmental alveolar opacity involving more likely the lower lobes in 55 patients, and multiple or interstitial opacities in the others. Chest radiographs were considered normal in eight patients. The clinical response was favorable in all the patients with a reduction in fever 4.8+/-3.9 days after the start of treatment with the second antibiotic that included mainly erythromycin or quinolones, and chest radiographs returned to normal in 81% of the patients within the first month.

Acute Disease↗

[Desquamative interstitial pneumopathy: a rare form of diffuse interstitial pneumopathy].

Desquamative interstitial pneumonia (PID) is a rare disorder initially described by Liebow in 1965. It is characterised by the presence of an interstitial pneumonia consisting of minimal lesions of interstitial fibrosis and by the accumulation of a rich intraalveolar cellular material principally composed of macrophages. Numerous aetiologies have been found particularly that due to long term Nitrofurantoin. We report the observation of a 57 year old patient, a cigarette smoker, in whom the diagnosis of PID was made after histological examination of a lung biopsy. Based on this observation the pathogenesis and possible different aetiologies of PID are discussed.

Anti-Infective Agents, Urinary↗

[Osseous site of systemic cryptococcosis in an immunocompetent patient].

Cryptococcosis is a cosmopolite mycosis caused by an opportunistic fungus usually infecting immunodeficient subjects. A 50-year old patient, with no particular medical history was seen with metaphyseal and diaphyseal bony lesions of a non-specific lytic aspect. This demonstrates that such an infection may also occur in apparently immunocompetent subjects. Diagnosis may be difficult and needs a special investigation looking for Cryptococcus neoformans. It should perhaps be made when first-intention investigations of a lytic bony lesion does not reveal any precise aetiology.

Cryptococcosis↗

[Current role of aminoglycosides in the treatment of acute pyelonephritis].

In view of the very great efficacy of 3rd generation cephalosporins and fluoroquinolones used as monotherapy in the treatment of uncomplicated acute pyelonephritis, the addition of an aminoglycoside is not currently recommended, because of the unfavourable balance of the advantages and disadvantages of this antibiotic class. However, a brief course of aminoglycosides may nevertheless be useful during the initial phase of treatment, especially in hospitalised subjects. The authors analyse the contribution of three recently published studies to this debate.

Acute Disease↗

Influence of erythromycin resistance, inoculum growth phase, and incubation time on assessment of the bactericidal activity of RP 59500 (quinupristin-dalfopristin) against vancomycin-resistant Enterococcus faecium.

RP 59500, a mixture of two semisynthetic streptogramin antibiotics (quinupristin and dalfopristin), is one of a few investigational agents currently in clinical trials with inhibitory activity against multiple-drug-resistant strains of Enterococcus faecium. We evaluated the bactericidal activity of this antimicrobial against 30 recent clinical isolates of vancomycin-resistant E. faecium, including 23 erythromycin-resistant (MIC, >256 microg/ml) and 7 erythromycin-intermediate (MIC, 2 to 4 microg/ml) strains. All isolates were inhibited by RP 59500 at 0.25 to 1.0 microg/ml. The bactericidal activity of RP 59500 was markedly influenced by the erythromycin susceptibility of the strains and by several technical factors, such as inoculum growth phase and time of incubation of counting plates. As determined by time-kill methods, RP 59500 at a concentration of 2 or 8 microg/ml failed to kill erythromycin-resistant organisms under any conditions. Bactericidal activity was observed against all seven erythromycin-intermediate isolates when log-phase inocula were used and the cells were counted after 48 h of incubation (mean reductions in viable bacteria for RP 59500 at concentrations of 2 and 8 microg/ml, 3.45 and 3.50 log10 CFU/ml, respectively), but killing was diminished when the plates were examined at 72 h (mean killing, 3.06 and 2.95 log10, CFU/ml, respectively). No bactericidal activity was observed when stationary-phase cultures were used. On the basis of these data, we expect that bactericidal activity of RP 59500 against the multiple-drug-resistant E. faecium strains currently encountered would be distinctly uncommon.

Anti-Bacterial Agents↗

Sequence-specific epigenetic effects of the maternal somatic genome on developmental rearrangements of the zygotic genome in Paramecium primaurelia.

In ciliates, the germ line genome is extensively rearranged during the development of the somatic macronucleus from a mitotic product of the zygotic nucleus. Germ line chromosomes are fragmented in specific regions, and a large number of internal sequence elements are eliminated. It was previously shown that transformation of the vegetative macronucleus of Paramecium primaurelia with a plasmid containing a subtelomeric surface antigen gene can affect the processing of the homologous germ line genomic region during development of a new macronucleus in sexual progeny of transformed clones. The gene and telomere-proximal flanking sequences are deleted from the new macronuclear genome, although the germ line genome remains wild type. Here we show that plasmids containing nonoverlapping segments of the same genomic region are able to induce similar terminal deletions; the locations of deletion end points depend on the particular sequence used. Transformation of the maternal macronucleus with a sequence internal to a macronuclear chromosome also causes the occurrence of internal deletions between short direct repeats composed of alternating thymines and adenines. The epigenetic influence of maternal macronuclear sequences on developmental rearrangements of the zygotic genome thus appears to be both sequence specific and general, suggesting that this trans-nucleus effect is mediated by pairing of homologous sequences.

Animals↗

Long-term evolution of daytime somnolence in patients with sleep apnea/hypopnea syndrome treated by continuous positive airway pressure.

We demonstrated in a previous study that excessive daytime sleepiness (EDS) in patients who have sleep apnea/hypopnea syndrome (SAHS) and are undergoing continuous positive airway pressure (CPAP) treatment improved differently in two groups of patients: in group I, multiple sleep latency tests (MSLT) were normalized after 50 days of treatment (individual value > 10 minutes), whereas they remained low (individual value < 10 minutes) in group II, with a significant difference between groups. To evaluate the long-term evolution of daytime somnolence under nasal CPAP treatment, five patients from group I and seven patients from group II underwent a new polysomnography and MSLT 4 years after the previous study. Clinical, polysomnographic and MSLT results obtained at baseline before treatment (T1), after the initial 50-day period of CPAP treatment (T2), and after 4 years (T3) were compared. The significant difference in mean MSLT value between the two groups previously observed at T1 and T2 disappeared at T3 (group I: 12.4+/-5.9 minutes; group II: 9.7+/-5.9 minutes). We found that this long-term improvement in excessive daytime somnolence was independent of the initial MSLT value, the severity of SAHS, and the initial MSLT changes under nasal CPAP. Long-term MSLT evolution was significantly correlated to CPAP compliance. These results demonstrate that even in the absence of a significant increase in MSLT at the beginning of CPAP treatment, further improvement is still possible several years later, which may encourage the regular, long-term use of nasal CPAP by patients.

Aged↗

DNA: an extensible molecule.

The force-displacement response of a single duplex DNA molecule was measured. The force saturates at a plateau around 70 piconewtons, which ends when the DNA has been stretched about 1.7 times its contour length. This behavior reveals a highly cooperative transition to a state here termed S-DNA. Addition of an intercalator suppresses this transition. Molecular modeling of the process also yields a force plateau and suggests a structure for the extended form. These results may shed light on biological processes involving DNA extension and open the route for mechanical studies on individual molecules in a previously unexplored range.

Chemical Phenomena↗

Effects of two oral erythromycin ethylsuccinate formulations on the motility of the small intestine in human beings.

Fourteen-membered macrolides are known to produce alterations in digestive tract motor activity; these include the induction of strong gastric contractions and a decrease in the motility of the small intestine. The aim of the study was to compare the effects of two different formulations of erythromycin ethylsuccinate (EE) on duodenojejunal motility. Compared with the more commonly used crystalline formulation of EE (CEE), the amorphous formulation (AEE) has previously been described to have greater bioavailability and to induce significantly fewer gastrointestinal side effects when given at therapeutic and what have been considered to be equivalent oral doses (i.e., CEE, 1,000 mg every 12 h; AEE, 500 mg every 12 h). In a crossover double-blind study, duodenojejunal manometric recordings were performed for 10 volunteers treated with placebo, CEE at 1,000 mg, or AEE at 500 mg. Recordings for each volunteer were obtained for a fed period after a standard dinner and then for a nocturnal fasting period. When compared with the placebo, CEE significantly decreased the motility index of the duodenum during the 30 min after the peak serum erythromycin concentrations, shortened the duration of the fed state, and had no effect during the fasting state. In contrast, AEE did not significantly modify any motility parameter. Because AEE produced significantly lower concentrations in serum than CEE, these results do not necessarily imply that the two formulations of EE act differently on the motility of the small intestine.

Administration, Oral↗

Good immunogenicity of GBM strain inactivated hepatitis A vaccine in healthy male adults.

A formalin-inactivated aluminium hydroxide adsorbed hepatitis A vaccine was evaluated in a dose-response study on 195 healthy male adults (age range: 18-31 years) in two French hospitals (Lyon, Rouen). Four doses (20, 40, 80, 160 RIA antigen units) were administered intramuscularly (i.m.) in two injections over a 6-month period. At the time of the first vaccine injection, 32 subjects (16.4%) were found positive (> 20 mIU ml-1) for HAV antibody (total Ig RIA HAVAB assay, Abbott Laboratories) and were excluded from the analysis of immunogenicity criteria. Fourteen days after the first vaccine injection, 78.1% (95% confidence interval (CI): 62-90) of seronegative subjects who received the 160 RIA antigen unit dose seroconverted with a geometric mean titre (GMT) of 43 mIU ml-1 (95% CI: 33-56). Seroconversion was 100% (95% CI: 91-100) at 1 month with a GMT of 95 mIU ml-1 (95% CI: 79-112). Statistical analysis revealed a significant dose-related effect (p < 0.0001) on GMT by multivariate regression analysis of the results after the first injection. Biological safety was evaluated and alanine aminotransferase and aspartate aminotransferase levels were similar prior to and 14 days after the first injection in the four groups. Reactions after injection were similar in the four dosage groups: 6.2% of subjects reported immediate reactions after first vaccination (feeling sick, spontaneous pain, headache), 8.9% reported local reactions at the site of injection (spontaneous pain, haematoma, local adenopathy) and 13.5% reported general reactions ('flu-like' syndrome, gastrointestinal tract disorders, fatigue, headache).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Comparison of different beta-lactam-glycopeptide-gentamicin combinations for an experimental endocarditis caused by a highly beta-lactam-resistant and highly glycopeptide-resistant isolate of Enterococcus faecium.

A synergistic bactericidal effect between penicillin, vancomycin, and gentamicin has been described against enterococci highly resistant to beta-lactams and glycopeptides. Since such a synergy was also observed in vitro between ceftriaxone, teicoplanin, and gentamicin against Enterococcus faecium 70/90, the efficacy of different combinations including penicillin or ceftriaxone, vancomycin or teicoplanin, and gentamicin was compared in vivo in experimental endocarditis. In vitro, all four triple combinations provided a bactericidal effect. In rabbits, after a 5-day treatment, the ceftriaxone-vancomycin-gentamicin combination was the most effective, both in reducing the total bacterial titers and in eradicating the subpopulation resistant to the synergy. Compared with the 5-day regimen, 10- and 20-day regimens of ceftriaxone-vancomycin-gentamicin, each followed by a 3-day antibiotic-free period, increased the number of sterilized animals but failed to avoid the emergence of resistant bacteria, which occurred in 10%-20% of animals.

Animals↗