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Biomedical subjects

M Estenne

Publications and source records attributed to M Estenne.

At least 19 recordsLinked to original sources

Impaired antigen-presenting cell function contributes to T-cell hyporesponsiveness in stable lung transplant recipients.

BACKGROUND: Peripheral blood mononuclear cells (PBMC) of stable renal or cardiac transplant recipients were previously shown to respond to allogeneic cells but not to soluble protein antigens. The aim of the present study was to assess the T-cell and antigen-presenting cell (APC) functions of stable lung transplant (LT) recipients. METHODS: We obtained PBMC from 38 stable LT recipients. PBMC from healthy volunteers served as controls. PBMC were stimulated with either anti-CD3 monoclonal antibody, allogeneic PBMC, or tetanus toxoid (TT). T-cell activation was assessed by determination of interleukin (IL)-2 levels in culture supernatants; in some experiments, interferon-y levels were also determined. Patients' APC function was tested in a mixed leukocyte reaction using patients' PBMC as stimulators. The expression of class II MHC, B7.2, and CD40 molecules on patients' APC was determined by flow cytometry, and their production of IL-10 and IL-12 at the basal state and upon CD40 ligation was also measured. RESULTS: Patients' T cells produced normal amounts of IL-2 in response to anti-CD3 monoclonal antibody and allogeneic PBMC. In contrast, the response of memory T cells to TT was severely blunted both in terms of IL-2 and interferon-y production. Patients' PBMC were poor stimulators in mixed leukocyte reaction, and class II MHC expression on patients' monocytes was significantly reduced. Patients' APC presented a modest but significant increase in basal IL-10 production and produced significantly less IL-12 upon CD40 ligation than control APC. CONCLUSIONS: T cells from stable LT recipients respond normally to stimuli that do not depend on autologous APC. The major impairment in the T-cell response to TT is caused by APC dysfunction, which involves decreased class II MHC expression and deficient IL-12 synthesis.

Antigen-Presenting Cells↗

Effect of preoperative hyperinflation on static lung volumes after lung transplantation.

It is still not known whether persistent increases in functional residual capacity (FRC) and residual volume (RV) after lung transplantation are due to preexisting hyperinflation. Therefore, the aim of this study was to determine the effects of chronic lung hyperinflation on static lung volumes after heart/lung (HLT) and bilateral lung transplantation (BLT). Static lung volumes were measured in 33 patients before and at 6 month intervals for up to 3 yrs after HLT (n=25) or BLT (n=8). The preoperative diagnosis was cystic fibrosis in 25 patients and other chronic hyperinflated lung diseases in eight patients. After surgery, total lung capacity returned to predicted normal values but FRC and RV remained greater than expected for either the recipient or the donor. At 1 yr after surgery, mean+/-SD FRC and RV were 130+/-18% and 151+/-34% of the predicted values for the recipient (p<0.001), and these figures did not change significantly over time. Similar abnormalities were found in patients with and without cystic fibrosis. After transplantation for lung diseases producing chronic hyperinflation, there is a persistent increase in functional residual capacity and residual volume. This alteration is present in patients operated on for diseases developed in both childhood and adulthood and is not recovered over time. It may be due to irreversible changes in the structure of the ribcage.

Adult↗

Obliterative bronchiolitis after lung transplantation.

Despite marked improvements in early survival, long-term outcome after lung transplantation is still threatened by obliterative bronchiolitis (OB). Thought to be a manifestation of chronic allograft rejection, OB affects up to 65% of patients at 5 years after surgery and produces a relentless airflow obstruction. Early and late acute rejection are the primary risk factors for OB, but cytomegalovirus infection and airway ischemia may also play a role. In most patients, OB responds poorly to augmented immunosuppression and eventually leads to infectious complications and terminal respiratory failure. Because early diagnosis is associated with better prognosis, every effort should be made to detect OB in a preclinical stage. This may be best achieved by combining several techniques, such as surveillance transbronchial biopsy and bronchoalveolar lavage, measurements of ventilation distribution and exhaled nitric oxide, and expiratory computed tomography.

Anti-Inflammatory Agents↗

Abdominal muscle strength in patients with tetraplegia.

The abdominal muscles are completely paralyzed after traumatic transection of the cervical cord. To assess the residual pressure-generating capacity of these muscles, we first measured the changes in gastric pressure (DeltaPga) during paired bilateral stimulation of the lower thoracic nerve roots in eight chronic patients with C5-C7 tetraplegia and eight matched unaffected subjects in the seated posture. Stimulations were applied with a 90-mm circular magnetic coil positioned at the level of T10 and connected to a Magstim 250 stimulator. During relaxation at FRC, DeltaPga during maximal stimulation averaged (mean +/- SE) 76.0 +/- 11.7 cm H(2)O in the control subjects, whereas in the patients it was only 29.9 +/- 3.7 cm H(2)O (p = 0.002). Stimulations were next applied during the course of a forced expiration. All patients consistently demonstrated an abrupt increase in esophageal pressure (22.7 +/- 4.5 cm H(2)O), and six of them also showed an increase in expiratory flow. The cumulative thickness of the four abdominal muscles, as measured with an ultrasound probe, was 34% smaller in the patients than in the control subjects and correlated positively with maximal DeltaPga. We conclude that in patients with tetraplegia, muscle atrophy causes a marked reduction in abdominal muscle strength. However, magnetic stimulation of the abdominal muscles elicits increases in intrathoracic pressure that are greater than those required to initiate dynamic airway compression; it might, therefore, improve the clearing of airway secretions.

Abdominal Muscles↗

Detection of obliterative bronchiolitis after lung transplantation by indexes of ventilation distribution.

Obliterative bronchiolitis (OB) is the first cause of death of long-term survivors of lung transplantation. The diagnosis is based on pathology and/or on an irreversible decrease in forced expiratory volume in 1 s (FEV(1)) below 80% of the best postoperative value. We tested whether indexes of ventilation distribution may provide evidence of OB before conventional pulmonary function tests (PFTs). Fifty-seven patients with heart-lung (n = 47) or double-lung (n = 10) transplantation were monitored with conventional PFTs and measurements of the slope of the alveolar plateau for He (S(He)), SF(6) (S(SF6)), and N(2) (S(N2)) obtained during single-breath washouts. The date at which a functional variable showed an irreversible change outside the 97.5% confidence interval was compared with the date at which a greater than 20% fall in FEV(1) was observed. A total of 1,929 tests (median, 30 tests per patient) were performed during the 1,215 d (range, 164-2,829 d) of follow-up. Eighteen patients showed an irreversible and greater than 20% fall in FEV(1) during the course of the study. This alteration was preceded by a rise in S(He) in 17 patients and by a rise in S(N2) in 16 patients, which indicated a more heterogeneous ventilation. The median time interval between the change in S(He) and S(N2) and the 20% decrease in FEV(1) was 356 and 168 d, respectively, with seven patients showing an interval of 18 mo or more. Conventional PFTs, including midexpiratory flow rates, deteriorated after indexes of ventilation distribution. Thirty-nine patients did not show any significant and irreversible alteration in conventional PFTs over the study period; only seven of these patients developed significant alterations in ventilation distribution. We conclude that measurements of ventilation distribution detect posttransplant OB much earlier than conventional PFTs.

Adult↗

[The respiratory muscles in emphysema. The effects of thoracic distension].

Besides increasing the work of ventilation, emphysema increases lung volume which in itself has a deleterious effect on the inspiratory muscles. We review here the effects of an acute change in lung volume on the configuration of the rib cage and muscle function. We also discuss the effects of the chronic distension associated with emphysema. The effects produced by changes in muscle length and configuration on the mechanical force and action of inspiratory muscles is detailed with particular focus on the diaphragm and its structural adaptations to experimental emphysema. We also analyze the activation pattern of inspiratory and expiratory muscles during the breathing process in patients with emphysema. Finally, we discuss the effects of single-lung transplantation and reduction surgery on chest distension and improved inspiratory muscle function.

Adaptation, Physiological↗

[Primary and isolated cutaneous lymphomatoid granulomatosis following heart-lung transplantation].

BACKGROUND: Lymphomatoid granulomatosis is an Epstein-Barr virus-associated B-cell lymphoproliferative disease. It is angiocentric and angiodestructive and involves the lungs, central nervous system and skin. Exclusive cutaneous involvement is rare and may be associated with a better outcome. Contrarily to the extra-cutaneous forms of lymphomatoid granulomatosis, it is difficult or impossible to detect Epstein-Barr virus DNA sequences in primary and isolated cutaneous lymphomatoid granulomatosis. CASE REPORT: A 54-year-old woman developed erythemato-violaceous lesions on both legs 3 years after a heart-lung transplantation. The diagnosis of erythema multiforme and of drug-induced vasculitis were first made. Because of fever and of the rapid extension of the lesions, the patient was hospitalized. The histologic examination of the first lesions showed a perivascular infiltrate, without epidermotropism, composed of histiocytes, lymphocytes and plasma cells. Immunohistochemistry revealed the presence of a predominantly T-cell infiltrate with some large B cells. Subsequent biopsies were diagnosed as high grade B-cell lymphoma. Polymerase chain reaction analysis as well as in situ hybridation study showed the presence of Epstein-Barr virus load in the lesions. There was however no serologic evidence of viral reactivation. Extensive systemic evaluation revealed no visceral or bone marrow involvement. Despite antiviral treatment and CHOP polychemotherapy, the patient died 3 months after her admission. DISCUSSION: This observation of lymphomatoid granulomatosis is particular because of its exclusive cutaneous involvement associated with a fulminant evolution to high grade B lymphoma. The presence of a context of iatrogenic immunosuppression underlies the role of altered immune cellular functions in the initiation and/or progression of lymphomatoid granulomatosis and strengthens the role of a viral agent in its pathogenesis. We suggest that the presence of Epstein-Barr virus, which is generally not associated with the isolated cutaneous forms of lymphomatoid granulomatosis, may have played a role in this fulminant evolution to high grade B lymphoma.

Diagnosis, Differential↗

Volume of graft and native lung after single-lung transplantation for emphysema.

To assess how the presence of the hyperinflated native lung influences the volume of the graft after single-lung transplantation (SLT) for emphysema, we used chest computed tomography to measure the TLC of each lung at a mean of 326 d before and 239, 588, and 932 d after SLT in nine patients. In addition, we obtained measurements of TLC and FRC in these nine patients plus one additional recipient at 697 d after surgery, and in 10 nonsmoking normal subjects matched for age, sex, height, and weight. On the nontransplanted side, TLC averaged 3.57 L before and 3.73 L, 3.70 L, and 3.73 L after SLT (NS). Corresponding values on the transplanted side were 3.42 L before and 2.06 L, 1.96 L, and 1.90 L after surgery, respectively (p < 0. 0002). Compared with the values obtained on the ipsilateral side in the control subjects, the FRC of the graft amounted to 100%, but its TLC was decreased to 79% (p < 0.005). We conclude that (1) the TLC of the graft and of the native lung do not change over time after SLT for emphysema, and (2) compared with the ipsilateral lung in normal control subjects, the TLC of the graft is substantially reduced, but its FRC is within normal limits.

Female↗

Diaphragm dimensions after single-lung transplantation for emphysema.

We used three-dimensional reconstructions obtained with spiral computed tomography to measure total diaphragm surface area (Adi), and the surface area of the dome (Ado) and of the zone of apposition (Aap) of the diaphragm in nine patients with single-lung transplantation (SLT) for emphysema and nine normal subjects matched for age, sex, height, and weight. Measurements were obtained at supine FRC, midinspiratory capacity, and TLC. In the normal subjects, Ado and Adi were greater on the right than on the left side, and the right dome was positioned more cranially than the left one, presumably because of the presence of the liver. Compared with either the ipsilateral side in the controls or the native side in the patients, Ado was smaller on the transplanted side because the mediastinum was shifted toward the graft. Adi showed a similar trend. On the other hand, the radius of curvature of the dome in the coronal and sagittal planes was similar on the side of the graft and on the ipsilateral side in the controls. In conclusion, we found that after SLT for emphysema, diaphragm configuration comes back to normal but Ado, and with it Adi, remain smaller than in normal subjects because the mediastinum is displaced toward the graft.

Adult↗

Haemodynamic response to dynamic exercise after heart-lung transplantation.

The purpose of this study was to investigate the haemodynamic response to dynamic exercise after heart-lung transplantation (HLT). Nine stable HLT recipients (6 males) were studied 12-55 months after transplantation. While sitting on a cycle ergometer, they first underwent a maximal symptom-limited exercise test (power increment was 10 W x min(-1)) to determine the maximal tolerable workload. On the next day, they performed a second exercise test at 0, 40, 60 and 80% of their predetermined maximal workload (mean+/-sD: 108+/-20 W). Stage duration was 6 min. Respiratory, gas exchange, and haemodynamic measurements were performed at rest, during the last minute of each stage, and after recovery. Haemodynamic variables at rest were within normal limits except heart rate (HR) which was greater and stroke volume index (SVI) which was lower than normal. Peak oxygen consumption was 61+/-8% of predicted. HR showed an initial slow increase followed by a steeper rise, and a delayed return to baseline during the recovery period. SVI and cardiac index (CI) increased at the onset of exercise but did not change significantly at 40-80% of the maximal workload. Pulmonary capillary wedge pressure increased from 4+/-2 mmHg at rest to 14+/-3 mmHg at maximal exercise. It is concluded that during dynamic exercise, heart-lung transplantation recipients demonstrate a chronotropic incompetence, a reduced increase in cardiac index and stroke volume index, and an excessive rise in left ventricular filling pressures. These alterations may contribute to the persistent exercise limitation.

Adult↗

Gastric perforation due to mucormycosis after heart-lung and heart transplantation.

BACKGROUND: Gastrointestinal complications are a well-documented source of morbidity and mortality after heart and lung transplantation. METHODS: We report on two patients who presented with gastric perforation caused by mucormycosis during the first 2 months after heart-lung and heart transplantation. RESULTS: In the first patient, the clinical presentation was insidious and the diagnosis was made at an advanced stage of the disease. Despite surgery and aggressive antifungal treatment, the patient died. In the second patient, the diagnosis was made promptly, but despite antifungal treatment, he presented with gastric perforation within a week. CONCLUSIONS: These cases illustrate that fungal invasive disease may be a cause of early gastrointestinal perforation after solid organ transplantation.

Adult↗

Respiratory mechanics and gas exchange during one-lung ventilation for thoracic surgery: the effects of end-inspiratory pause in stable COPD patients.

OBJECTIVE: To examine the effects of end-inspiratory pause (EIP) of different durations on pulmonary mechanics and gas exchange during one-lung ventilation (OLV) for thoracic surgery. DESIGN: A prospective clinical study. SETTING: A university hospital. PARTICIPANTS: Eleven patients undergoing elective pulmonary resection with pulmonary hyperinflation on their preoperative pulmonary function studies. INTERVENTIONS: Patients were anesthetized, paralyzed, and intubated with a double-lumen endotracheal tube. Their lungs were ventilated with a Siemens 900C ventilator (Siemens; Solna, Sweden), with constant inspiratory flow. Tidal volume, respiratory rate, and inspiratory time were kept constant during the study. MEASUREMENTS AND RESULTS: During one-lung ventilation in the lateral decubitus position, three levels of EIP (0%, 10%, and 30%) were applied to the dependent lung in random order. After 15 minutes on the given ventilatory pattern, end-inspiratory and end-expiratory occlusions of at least 5 seconds were performed to obtain respiratory mechanics data. Arterial blood gas samples were drawn to assess gas exchange. Altering the duration of end-inspiratory pause from 0% to 30% resulted in a significant increase in intrinsic positive end-expiratory pressure (PEEPi) from 4.1 cm H2O to 7.0 cm H2O. Arterial oxygenation was significantly decreased from 109.7 to 80.5 mmHg and there was a significant negative correlation between the value of partial pressure of arterial oxygen (PaO2) and PEEPi by altering the duration of end-inspiratory pause. From the preoperative pulmonary function studies, the value of functional residual capacity (FRC) (% predicted) showed a significant negative correlation with the PaO2 changes. Partial pressure of arterial carbon dioxide (PaCO2) was not altered significantly by increasing the duration of end-inspiratory pause. CONCLUSION: During the period of OLV in the lateral position of patients with preexisting pulmonary hyperinflation, the magnitude of PEEPi increased and oxygenation decreased significantly, whereas the efficacy of ventilation was not changed by the addition of an end-inspiratory pause to the ventilatory pattern. Because arterial oxygenation is affected by the presence of pulmonary hyperinflation, the method of ventilation should take into account the magnitude of preoperative pulmonary hyperinflation.

Aged↗

Chest wall mechanics in sustained microgravity.

We assessed the effects of sustained weightlessness on chest wall mechanics in five astronauts who were studied before, during, and after the 10-day Spacelab D-2 mission (n = 3) and the 180-day Euromir-95 mission (n = 2). We measured flow and pressure at the mouth and rib cage and abdominal volumes during resting breathing and during a relaxation maneuver from midinspiratory capacity to functional residual capacity. Microgravity produced marked and consistent changes (Delta) in the contribution of the abdomen to tidal volume [DeltaVab/(DeltaVab + DeltaVrc), where Vab is abdominal volume and Vrc is rib cage volume], which increased from 30.7 +/- 3. 5 (SE)% at 1 G head-to-foot acceleration to 58.3 +/- 5.7% at 0 G head-to-foot acceleration (P < 0.005). Values of DeltaVab/(DeltaVab + DeltaVrc) did not change significantly during the 180 days of the Euromir mission, but in the two subjects DeltaVab/(DeltaVab + DeltaVrc) was greater on postflight day 1 than on subsequent postflight days or preflight. In the two subjects who produced satisfactory relaxation maneuvers, the slope of the Konno-Mead plot decreased in microgravity; this decrease was entirely accounted for by an increase in abdominal compliance because rib cage compliance did not change. These alterations are similar to those previously reported during short periods of weightlessness inside aircrafts flying parabolic trajectories. They are also qualitatively similar to those observed on going from upright to supine posture; however, in contrast to microgravity, such postural change reduces rib cage compliance.

Abdomen↗

Effects of abdominal strapping on forced expiration in tetraplegic patients.

Patients with traumatic transection of the lower segments of the cervical cord contract the clavicular portion of the pectoralis major during forced expiration and cough, and the rise in intrathoracic pressure resulting from this contraction produces dynamic airway compression in many patients. Because the abdominal muscles are paralyzed, however, there is paradoxical expansion of the abdomen, which may reduce the rise in intrathoracic pressure and the degree of airway collapse. To evaluate the magnitude of this effect, we measured expiratory flow rate (Vexp) and esophageal pressure (Pes) during a series of forced expiratory vital capacity maneuvers and constructed isovolume-pressure flow (IVPF) curves before and after abdominal strapping in eight C5-8 tetraplegic subjects. Strapping produced small and inconsistent changes in maximal Vexp and Pes and resulted in the development of small flow plateaus in only four patients. In tetraplegic subjects, abdominal strapping thus has small effects on forced expiration and is unlikely, therefore, to improve the efficiency of cough.

Abdominal Muscles↗

Neck and abdominal muscle activity in patients with severe thoracic scoliosis.

Patients with severe chronic obstructive pulmonary disease (COPD) do not use the sternocleidomastoid muscles when breathing at rest, but have a greater than normal neural drive to the rib-cage inspiratory muscles, the abdominal muscles, and the diaphragm. Yet the increased activation of the abdominal muscles and diaphragm in such patients has only limited mechanical effects, and this has led to the suggestion that the overall increase in neural drive is simply an automatic response of the respiratory system to a greater than resting stimulation. To test this hypothesis, we examined the pattern of respiratory-muscle activation in eight patients with severe thoracic scoliosis (Cobb angle between 100 degrees and 136 degrees). We recorded electromyograms of the sternocleidomastoid, scalene, rectus abdominis, external oblique, and transversus abdominis muscles; esophageal (Pes) and gastric (Pga) pressures; and the anteroposterior (AP) diameter of the abdomen during resting breathing in the seated posture. All patients had invariable phasic inspiratory activity in the scalenes; and five patients had invariable phasic expiratory activity in the transversus; intermittent expiratory activity in the transversus was also recorded in three patients. In contrast, only one patient had invariable phasic inspiratory activity in the sternocleidomastoid, and only one patient had invariable phasic expiratory activity in the external oblique. The decrease in abdominal AP diameter during expiration was commonly associated with a rise in Pga. These observations therefore indicate that the pattern of respiratory-muscle activation in patients with severe thoracic scoliosis is essentially similar to that seen in patients with severe COPD. This supports the concept that the order of recruitment of the respiratory muscles during breathing is an automatic response of the central controller.

Abdominal Muscles↗