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Biomedical subjects

D Leduc

Publications and source records attributed to D Leduc.

At least 19 recordsLinked to original sources
PubMed2006

Lamb wave propagation in a plate with a grooved surface with several spatial periodicities.

In order to investigate non-destructively the bonding between rough plates, the problem of Lamb waves propagating on a rough plate is addressed in this paper. Numerical analysis is performed on periodical gratings made of identical triangular grooves. If the surface profile is made up of grooves with one periodicity, then a mode conversion is observed. In the wave-number/frequency space, a phonon relation is written between phonons related to the grating and to the incident and reflected-converted modes. If the grooved surface is made up of several spatial periodicities, then the phonon relation is still verified. Signal processing allows us to give an interpretation of the results in the dual space (wave-number/frequency). An experimental study is also performed to corroborate the numerical predictions.

Journal Article↗
PubMed2005

[Manual abdominal compression for the detection of expiratory flow limitation].

INTRODUCTION: Expiratory flow limitation (EFL) is a characteristic feature of chronic obstructive pulmonary disease (COPD) and leads to dynamic hyperinflation (DH) which is a major source of dyspnoea, particularly during exercise. STATE OF THE ART: A new technique for the detection of EFL, based on manual compression of the abdomen (MCA), was assessed both in normal subjects and patients with COPD. MCA was always associated with a moderate increase in pleural pressure and allowed the detection of EFL in a reproducible manner, in both the seated and supine postures. The technique was well tolerated. It was also a reliable method for the detection of EFL during exercise since EFL detection was effectively associated with the development of DH. Finally, MCA was also compared to NEP in patients with obstructive sleep apnoea syndrome (OSAS) and in these patients, MCA invariably increased expiratory flow whereas the NEP method produced flow limitation in some cases because of upper airway collapse. PERSPECTIVES: EFL detection with MCA may be clinically useful since EFL is a determinant of dyspnoea, affects ventilatory response to exercise as well as maximum exercise capacity. CONCLUSIONS: MCA is a reliable technique for the detection of EFL in different positions, during resting breathing or exercise, requiring neither special equipment nor patient cooperation.

Abdomen↗
PubMed2004

Two distinct pathways for thymidylate (dTMP) synthesis in (hyper)thermophilic Bacteria and Archaea.

The hyperthermophilic anaerobic archaeon Pyrococcus abyssi, which lacks thymidine kinase, incorporates label from extracellular uracil, but not from thymidine, into its DNA. This implies that P. abyssi must synthesize dTMP (thymidylate), an essential precursor for DNA synthesis, de novo. However, iterative similarity searches of the three completed Pyrococcus genomes fail to detect candidate genes for canonical thymidylate synthase ThyA, suggesting the presence of alternative pathways for dTMP synthesis. Indeed, by identifying a novel class of flavin-dependent thymidylate synthases, ThyX, we have recently proven that two distinct pathways for de novo synthesis of dTMP are operational in the microbial world. While both thyX and thyA can be found in hyperthermophilic micro-organisms, the phylogenetic distribution of thyX among hyperthermophiles is wider than that of thyA. In this contribution, we discuss the differences in the distinct mechanisms of dTMP synthesis, with a special emphasis on hyperthermophilic micro-organisms.

Archaea↗
PubMed2002

Expiratory flow limitation during exercise in COPD: detection by manual compression of the abdominal wall.

Manual compression of the abdomen (MCA) during spontaneous expiration is a simple method for the detection of flow limitation in the chronic obstructive pulmonary disease (COPD) patients during resting breathing, based on comparison of flow/volume curves obtained during MCA with that of the preceding control breath. It was assessed whether this nonstandardized technique is also feasible during exercise. MCA was performed during resting breathing and constant-exercise work at one- and two-thirds maximal mechanical power output (W'max) in six normal subjects and 12 COPD patients. Changes in end-expiratory lung volume (EELV) were also studied. With the aid of inspection, abdominal palpation and lung auscultation, MCA could always be applied during expiration. Flow limitation was never detected in the six normal subjects, whereas four of the COPD patients were flow limited at rest, seven during exercise at one-third W'max and nine during exercise at two-thirds W'max. Expiratory flow limitation detected by MCA was always associated with an increase in EELV during exercise, indicating dynamic hyperinflation occurrence or increase. It is concluded that manual compression of the abdomen is a very simple and reliable method for the detection of flow limitation during exercise.

Abdominal Wall↗
PubMed2002

Effect of chest wall vibration on the canine diaphragm during breathing.

High-frequency mechanical vibration of the ribcage reduces dyspnoea in patients with chronic obstructive pulmonary disease, and the suggestion has been made that this effect might be related to a decrease in central respiratory drive resulting from an increase in afferent inputs from intercostal muscles. In the present studies, the effects of ribcage vibration on central respiratory drive have been assessed without the confounding influence of conscious reactions. The electromyographic (EMG) activity of the diaphragm and the changes in pleural (Ppl) and abdominal (Pab) pressure were measured in six anaesthetized, spontaneously-breathing dogs while the rostral, the middle, or the caudal portion of the ribcage was vibrated at intervals during inspiration. The EMG activity of the external and parasternal intercostals was also measured. Ribcage vibration consistently elicited a marked increase in the inspiratory EMG activity recorded from the external intercostals, thus indicating that the procedure did activate intercostal muscle spindles. However, no alteration in diaphragmatic or parasternal intercostal EMG activity was seen in any animal. Transdiaphragmatic pressure and the relationship between deltaPab and deltaPpl during inspiration were also unaltered. The authors conclude that ribcage vibration and, with it, stimulation of external intercostal muscle spindles has no significant influence on phrenic motoneurones or on medullary inspiratory neurones. It is unlikely, therefore, that the beneficial effect of the procedure on dyspnoea results from a specific reduction in central respiratory drive.

Animals↗
PubMed2001

Response of the canine internal intercostal muscles to chest wall vibration.

Although high-frequency mechanical vibration of the rib cage reduces dyspnea, its effects on the respiratory muscles are largely unknown. We have previously shown that in anesthetized dogs, vibrating the rib cage during inspiration elicits a marked increase in the inspiratory electromyographic (EMG) activity recorded from the external intercostal muscles but does not affect tidal volume (VT). In the present studies, we have tested the hypothesis that the maintenance of VT results from the concomitant contraction of the internal interosseous (expiratory) intercostals. When the rib cage was vibrated (40 Hz) during hyperventilation-induced apnea, a prominent activity was recorded from the external intercostals but no activity was recorded from the internal intercostals, including when the muscles were lengthened by passive inflation. The internal intercostals remained also silent when vibration was applied during spontaneous inspiration, and the phasic expiratory EMG activity recorded from them was unaltered when vibration was applied during expiration. Thus, the internal interosseous intercostals in dogs are much less sensitive to vibration than the external intercostals, and they do not interfere with the action of these latter during rib cage vibration. This lack of sensitivity might be the result of a reflex inhibition of the muscle spindle afferents by afferents from external intercostal muscle spindles.

Animals↗
PubMed2001

Detection of expiratory flow limitation by manual compression of the abdominal wall.

We have assessed a new method, manual compression of the abdominal wall (MCA) during expiration, in the detection of expiratory flow limitation. Twelve stable patients with chronic obstructive pulmonary disease (COPD) and five normal subjects were studied during spontaneous breathing in the supine and seated posture. MCA was performed during expiration with one hand at the umbilical level and we measured flow, volume, pleural (Ppl) and gastric (Pga) pressures and abdominal anteroposterior (AP) diameter at the umbilical level with magnetometers. No increase in expiratory flow during MCA relative to the preceding breath despite associated increases in pressures was considered as indicating expiratory flow limitation. In seven additional patients with increased upper airway collapsibility (obstructive sleep apnea syndrome [OSAS]), MCA was compared with negative expiratory pressure (NEP). In normal seated subjects, MCA was associated with a decrease in abdominal AP dimension (mean +/- SD: -27 +/- 6%), an increase in Pga (14.7 +/- 7.4 cm H(2)O) and Ppl (6.2 +/- 2.2 cm H(2)O), and an increase in expiratory flow. MCA caused similar changes in abdominal AP dimension and pressures in seated patients with COPD but six of them (50%), including four patients with FEV(1) less than 1 L, had no increase in expiratory flow. In the supine posture, MCA always increased expiratory flow in normal subjects but four additional patients with COPD showed evidence of flow limitation. MCA invariably increased expiratory flow in patients with OSAS whereas the NEP method suggested flow limitation in some cases. We conclude that MCA is a very simple method that allows detection of flow limitation in different positions.

Abdominal Muscles↗
PubMed2000

Long-term hydroxyurea in combination with didanosine and stavudine for the treatment of HIV-1 infection. Swiss HIV Cohort Study.

OBJECTIVE AND METHODS: In 1998 we reported on a randomized comparison between stavudine plus didanosine plus placebo versus stavudine plus didanosine plus hydroxyurea (HU), in patients with a CD4 count of 200-500 x 10(6) cells/l. After 3 months, the HU group had a higher proportion of patients with viral load < 200 x 10 cells/l. At the end of the 3 months blinded period, patients in the placebo group had the option to add HU if their viral load remained > 200 x 10(6) cells/l. We report results after 24 months. RESULTS: Seventy-two patients were randomized to the HU arm, and a further 30 elected to add HU after 12 weeks. Twenty-four months after the start of the trial, only 25% of the 72 patients originally randomized to HU, and 20% of the 30 who added HU after week 12, were still taking it. The reasons for stopping HU were: lack of efficacy (45%), adverse events (37%) and patient or physician preference (18%). Side effects were more frequent in the didanosine/stavudine/HU group than in the didanosine/stavudine group: neuropathy (35 versus 15%, P< 0.02), fatigue (22 versus 7%, P< 0.01), and nausea or vomiting (26 versus 9%, P< 0.01). Of those who had discontinued HU, 73% were taking three drugs including a protease inhibitor. Patients who had started HU were compared with similar patients who had started protease inhibitors in the Swiss cohort. The probability of stopping HU was higher than the probability of stopping nelfinavir or indinavir, and similar to the probability of stopping ritonavir. CONCLUSION: HU increased the antiviral effect of stavudine plus didanosine. However, side effects were more frequent, and after 24 months the majority of patients had switched to protease inhibitor regimens.

Anti-HIV Agents↗
PubMed2000

Response of the canine inspiratory intercostal muscles to chest wall vibration.

High-frequency mechanical vibration of the rib cage reduces dyspnea, but the effect of this procedure on the respiratory muscles is largely unknown. In the present studies, we have initially assessed the electrical and mechanical response to vibration (40 Hz) of the canine parasternal and external intercostal muscles (third interspace) during hyperventilation-induced apnea. When the vibrator was applied to the segment investigated, prominent external intercostal activity was recorded in the seven animals studied, whereas low-amplitude parasternal intercostal activity was recorded in only four animals. Similarly, when the vibrator was applied to more rostral and more caudal interspaces, activity was recorded commonly from the external intercostal but only occasionally from the parasternal. The two muscles, however, showed similar changes in length. We next examined the response to vibration of the muscles in seven spontaneously breathing animals. Vibrating the rib cage during inspiration (in-phase) had no effect on parasternal intercostal inspiratory activity but induced a marked increase in neural drive to the external intercostals. For the animal group, peak external intercostal activity during the control, nonvibrated breaths averaged (mean +/- SE) 43.1 +/- 3.7% of the activity recorded during the vibrated breaths (p < 0.001). External intercostal activity during vibration also occurred earlier at the onset of inspiration and commonly carried on after the cessation of parasternal intercostal activity. Yet tidal volume was unchanged. Vibrating the rib cage during expiration (out-of-phase) did not elicit any parasternal or external intercostal activity in six animals. These observations thus indicate that the external intercostals, with their larger spindle density, are much more sensitive to chest wall vibration than the parasternal intercostals. They also suggest that the impact of this procedure on the mechanical behavior of the respiratory system is relatively small.

Animals↗
PubMed1999

Reflex inhibition of canine inspiratory intercostals by diaphragmatic tension receptors.

1. Electrical stimulation of phrenic afferent fibres in the dog elicits a reflex inhibition of efferent activity to the inspiratory intercostal muscles. However, electrical stimulation has a poor selectivity, so the sensory receptors responsible for this inhibition were not identified. 2. In the present studies, cranial forces were applied during spontaneous inspiration to the abdominal surface of the central, tendinous portion of the canine diaphragm to activate tension mechanoreceptors in the muscle. Vagal afferent inputs were eliminated by vagotomy. 3. The application of force to the central tendon caused a graded, reflex reduction in inspiratory intercostal activity, especially in external intercostal activity. This reduction was commonly associated with a decrease in inspiratory duration and was invariably attenuated after section of the cervical dorsal roots. 4. In contrast, no change in inspiratory intercostal activity was seen when high frequency mechanical vibration was applied to the central tendon to stimulate diaphragmatic muscle spindles. 5. These observations provide strong evidence that tension receptors in the diaphragm, but not muscle spindles, induce reflex inhibition of inspiratory intercostal activity. The expression of this reflex probably involves supraspinal structures.

Animals↗
PubMed1998

Systemic administration of endotoxin induces bronchopulmonary hyperreactivity dissociated from TNF-alpha formation and neutrophil sequestration into the murine lungs.

Bronchopulmonary hyperreactivity (BHR), an increased responsiveness to nonspecific bronchoconstrictor agents, is a well-known characteristic of bronchial asthma. It has been recently suggested that the severity of this disease is related to the endotoxin content of house dust. In the present report, it is shown that the i.p. administration of bacterial LPS to mice is followed by a marked early dose-dependent BHR in response to methacholine. The microscopic examination showed no ultrastructural lesions of the lungs or of the airways, but a marked neutrophil accumulation in the capillaries, as confirmed by an increase of the lung content in the neutrophil enzyme marker myeloperoxidase. In parallel, high levels of TNF-alpha were found in plasma as well as its transcripts in the lung tissues. Using immunologic (anti-TNF-alpha and anti-granulocyte Abs), and pharmacologic (dexamethasone and vinblastine) tools, it is demonstrated that BHR is apparently neither related to the presence of neutrophils in the pulmonary microvasculature nor to the synthesis of TNF-alpha.

Aerosols↗
PubMed1998

A placebo-controlled trial of didanosine plus stavudine, with and without hydroxyurea, for HIV infection. The Swiss HIV Cohort Study.

OBJECTIVE: To explore the short-term effects on surrogate markers for HIV progression of didanosine (ddl) plus stavudine (d4T), with or without hydroxyurea. DESIGN: Randomized, double-blinded, prospective study. SETTING: Swiss HIV Cohort Study. PATIENTS: A total of 144 patients (75% antiretroviral-naive) were studied (mean baseline HIV-1 RNA, 4.53 log10 copies/ml; mean CD4 cell count, 370 x 10(6)/l). INTERVENTION: Patients received ddl (200 mg twice daily) plus d4T (40 mg twice daily), with additional hydroxyurea (500 mg twice daily) or placebo. MAIN OUTCOME MEASURES: The primary endpoint was a reduction of viraemia below 200 copies/ml after 12 weeks. At that time, patients who did not reach the primary endpoint were withdrawn in the hydroxyurea arm, whereas patients in the placebo group had the option of adding hydroxyurea to ddl and d4T. All patients were followed until week 24. RESULTS: After 12 weeks, 54% of the patients randomized to hydroxyurea had viraemia below 200 copies/ml, compared with 28% on placebo (P < 0.001). Using an ultrasensitive assay with a limit of detection of 20 copies/ml, 19% of patients receiving hydroxyurea had viraemia levels below 20 copies/ml, compared with 8% on placebo (P = 0.05). Mean decrease in HIV-1 RNA was 2.3 and 1.7 log10 copies/ml for hydroxyurea and placebo groups, respectively (P = 0.001). Hydroxyurea was found to induce lymphopenia (-124 x 10(6)/l). Increase in CD4 cell counts was +28 x 10(6)/l during hydroxyurea treatment compared with +107 x 10(6)/l on placebo (P = 0.001). CONCLUSIONS: Hydroxyurea improved the antiviral activity of d4T and ddl over a 12-week period, but was associated with a smaller increase in CD4 cell counts due to hydroxyurea-induced lymphopenia.

Adult↗
PubMed1998

Turnover of CD4+ and CD8+ T lymphocytes in HIV-1 infection as measured by Ki-67 antigen.

We investigated CD4+ and CD8+ T cell turnover in both healthy and HIV-1-infected adults by measuring the nuclear antigen Ki-67 specific for cell proliferation. The mean growth fraction, corresponding to the expression of Ki-67, was 1.1% for CD4(+) T cells and 1.0% in CD8(+) T cells in healthy adults, and 6.5 and 4.3% in HIV-1-infected individuals, respectively. Analysis of CD45RA+ and CD45RO+ T cell subsets revealed a selective expansion of the CD8+ CD45RO+ subset in HIV-1-positive individuals. On the basis of the growth fraction, we derived the potential doubling time and the daily turnover of CD4+ and CD8+ T cells. In HIV-1-infected individuals, the mean potential doubling time of T cells was five times shorter than that of healthy adults. The mean daily turnover of CD4+ and CD8+ T cells in HIV-1-infected individuals was increased 2- and 6-fold, respectively, with more than 40-fold interindividual variation. In patients with <200 CD4+ counts, CD4+ turnover dropped markedly, whereas CD8+ turnover remained elevated. The large variations in CD4+ T cell turnover might be relevant to individual differences in disease progression.

Adult↗
PubMed1997

Toxicity, efficacy, plasma drug concentrations and protease mutations in patients with advanced HIV infection treated with ritonavir plus saquinavir. Swiss HIV Cohort Study.

OBJECTIVE: To assess the safety, efficacy and plasma drug levels of the combination of ritonavir plus saquinavir for the treatment of advanced HIV infection. DESIGN: Multicentre pilot study. PATIENTS: Eighteen protease inhibitor-naive patients, with intolerance or contraindication to reverse transcriptase inhibitors, a median CD4 cell count of 12 x 10(6)/l (range, 1-50 x 10(6)/l), and a median HIV viraemia of 5.25 log10 copies/ml (range, 4.00-6.13 log10 copies/ml). METHODS: Patients received 600 mg twice daily of both ritonavir and saquinavir. Viraemia was measured at baseline and at weeks 5, 9 and 13. Response was defined as a drop of viraemia of more than 1 log10 at week 5. Plasma drug levels were determined after at least 3 weeks of combined treatment: samples were collected before and 1, 2, and 4 h after the morning ingestion of both drugs. The protease gene was sequenced at baseline and under treatment. RESULTS: Among the 16 patients evaluable at week 5, 11 were responders, and among these patients, six remained responders at week 13 (two with undetectable viraemia). Study discontinuations were due to side-effects (n = 4), patient choice (n = 3), protocol violation (n = 1) and death (n = 1). Responders had higher drug levels than non-responders (P < 0.01 for saquinavir, P = 0.04 for ritonavir). In two non-responders, development of multiple new mutations at positions 10, 20, 48, 82, 84 and 90 was observed after 5-13 weeks. CONCLUSION: The response to ritonavir plus saquinavir in advanced HIV infection is unpredictable. A minority of patients respond with disappearance of HIV viraemia. In other patients, rapid cumulative emergence of protease mutations conferring resistance to treatment cannot always be prevented by good compliance and relatively high plasma drug levels.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Effect of antigen provocation of IL-5 transgenic mice on eosinophil mobilization and bronchial hyperresponsiveness.

We investigated whether allergen-induced eosinophil recruitment into mouse airways modifies the in vivo bronchopulmonary responses to standard agonists, and adaptation of a technique described for larger animals. Swiss, CBA, and IL-5 transgenic mice were immunized with ovalbumin and challenged intranasally after 14 days. Immunization alone was followed by increased eosinophil counts in bone marrow and blood, whereas antigenic challenge induced eosinophil infiltration in lungs and bronchoalveolar lavage fluid, which was suppressed by dexamethasone. Despite the high eosinophil counts, no bronchopulmonary hyperreactivity to methacholine or serotonin was detected 3 to 96 hours after antigenic provocation. Our results demonstrate that immunization augments the production of eosinophils by mice, which is further increased by antigenic challenge, but that eosinophil overproduction and lung infiltration, per se, are not sufficient to induce bronchopulmonary hyperreactivity, even in constitutively hypereosinophilic IL-5 transgenic mice.

Airway Resistance↗