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Biomedical subjects

H Shennib

Publications and source records attributed to H Shennib.

At least 73 records · Page 4Linked to original sources

Double-lung transplantation in children: a report of 20 cases. The Joint Marseille-Montréal Lung Transplant Program.

In the last 3 1/2 years, we have performed 20 double-lung transplantations in children between 7 and 16 years old (mean age, 13 years). One patient had primitive bronchiolitis obliterans and the other 19, cystic fibrosis. Eight patients were operated on in an emergency situation, 7 of them requiring ventilator support before transplantation. The procedures were en bloc double-lung transplantation in the first 11 patients with separate bronchial anastomoses in 10, and sequential bilateral lung transplantation in the later 9 patients. There were no operative deaths. Two patients died in the hospital on postoperative days 37 and 73, and there were four late deaths, which were due to infection, rejection, and bronchiolitis obliterans. The acceptable incidence of airway complications, the improvement in lung function of survivors, and the acceptable midterm survival make double-lung transplantation an acceptable alternative to heart-lung transplantation in children. However, in very small children, heart-lung transplantation may be preferable because of the size of the airway anastomoses at risk.

Adolescent↗

Lectin-dependent cell-mediated cytotoxicity and natural killer function in rejecting and infected lung allografts.

Differentiation between rejection and infection of lung allografts remains difficult. The effects of these two pathologic entities on the cytolytic activity of bronchoalveolar lavage (BAL) and PBL were investigated. Left lung allotransplantation was performed on 16 mongrel dogs of which 12 were available for complete studies. All animals received CA, AZA, and PRED for 2 weeks. Four grafts developed left lower lobe Gram negative pneumonia. The eight remaining recipients progressed gradually to severe rejection after acute reduction of immunosuppression. Cytolytic activity of blood and left lung BAL lymphocytes was quantitated by the natural killer (NK) and lectin-dependent cell-mediated cytotoxicity (LDCMC) assays. Two additional groups serving as controls were either given a 10-day course of immunosuppressants or had right lower lobe pneumonia induced by transbronchial inoculation of gram negative bacteria. Immunosuppressed control animals showed significant depression of PBL and BAL lymphocyte LDCMC and NK activity. Similarly, BAL lymphocytes expressed very low LDCMC in normal allografts (2.8 +/- 0.8%). Once rejection developed and progressed, LDCMC became significantly higher (15.6 +/- 2.2 and 52.7 +/- 2.8% in mild and severe rejection, respectively). There was no detectable NK activity in rejecting lung allografts. BAL lymphocytes from infected allografts, on the other hand, showed an elevation of both NK and LDCMC activity (9.1 +/- 1.1 and 14.6 +/- 1.0%, respectively). Similarly, bacterial pneumonia in control animals manifested an increase in NK and LDCMC activity in lung and blood. PBL lymphocytes of lung allograft recipients, however, had increased NK and LDCMC activity in both rejection and infection. LDCMC/NK activity ratio (LM/NK index) of lung lymphocytes was significantly higher in rejecting allografts (11.2 +/- 1.0 and 12.4 +/- 1.6 for mild and severe rejection, respectively) than in infected ones (1.2 +/- 0.3, P < 0.0001). It appears, from this study, that rejection of the lung allograft results in alterations in BAL lymphocyte phenotypes and functions that differ from those associated with bacterial infection. Such differences may be useful in distinguishing episodes of acute allograft rejection from bacterial infection.

Animals↗

Techniques for localization of pulmonary nodules for thoracoscopic resection.

Significant advances in surgical equipment, video monitoring, and endoscopic surgical techniques have expanded the role of thoracoscopy to include pulmonary resection. One limitation of the thoracoscopic technique is the loss of manual palpation to identify the nodule that is either too small or too deep beneath the pleural surface. We describe the techniques used in 300 thoracoscopic pulmonary resections that have aided in identification of pulmonary nodules. These techniques include careful preoperative assessment of the computed tomogram, preoperative injection of methylene blue, or a needle localizing system to identify the nodule. Intraoperative techniques include instrument palpation, digital palpation, and intraoperative ultrasonography. It should be possible to identify the majority of pulmonary nodules at the time of thoracoscopy with these localizing techniques. All nodules were successfully identified in our last 200 thoracoscopic resections.

Humans↗

Differential lung ventilation. Applications beyond the operating room.

Mechanical ventilatory support in the setting of unilateral lung disease offers unique problems in management. When the difference in airway resistance or lung compliance between the two lungs is exaggerated, conventional mechanical ventilation might lead to preferential ventilation with hyperexpansion of one lung and gradual collapse of the other. Differential ventilation has been advocated to avert this problem. We illustrate the use of this technique in the management of two patients with different underlying pathologic conditions.

Adult↗

Is lung retransplantation indicated? Report on four patients.

As more lung transplantations are performed, many patients will suffer graft failure and will be considered for retransplantation. This article reviews the case management reports of four patients who received lung or heart/lung retransplantation, with overall disappointing results. The pros and cons of lung retransplantation are discussed.

Adult↗

Neoadjuvant chemotherapy with cytosine arabinoside by continuous infusion and cisplatin for resectable squamous cell carcinoma of the esophagus.

The combination of cisplatin and cytosine arabinoside has been shown in experimental models to be synergistic. We conducted a pilot study of cytosine arabinoside and cisplatin in unresectable or metastatic cancer of the esophagus in five patients and found significant activity, also on visceral metastasis. Therefore, we decided to examine this combination in the neoadjuvant setting. Since January 1989, eight patients with squamous cell carcinoma esophageal cancer were treated with two cycles of cytosine arabinoside (50 mg/m2) by continuous infusion for 4 days and by cisplatin (100 mg/m2) on the 5th day. Their ages ranged from 54-79 years. One patient had Stage I, three had Stage II, and four had Stage III disease. Responses assessed by endoscopy and computed tomographic (CT) scan prior to surgery were three with partial response, three with minor response, and two with no response. Only six patients were surgically resectable after chemotherapy. Toxicity consisted of grade 3 (one patient) and grade 4 (two patients) neutropenia, grade 3 (three patients) anemia, and grade 3 (two patients) and grade 4 (three patients) thrombocytopenia. All patients had subjective improvement of dysphagia 4 weeks after chemotherapy. Median survival of the whole group was 7.5 months. We concluded that there was no evidence of synergy of these drugs given in this manner in esophageal carcinoma since the response rate was no different from that achieved with cisplatin alone.

Aged↗

Early cellular events in the lung allograft.

We hypothesized that ischemic insult to the lung allograft may render it more susceptible to rejection. Left canine single-lung allografts were subjected to usual periods of cold and warm ischemia (4 hours and 1 hour, respectively). Bronchoalveolar lavage and open lung biopsies were performed at 0, 1, 4, and 24 hours and 1 week after transplantation. Bronchoalveolar lavage fluid was examined for cellular phenotypes, lymphocyte lectin-mediated cytotoxicity, and natural killer cell cytotoxicity. Open lung biopsy specimens were examined for severity of injury/rejection and MHC class II expression. Within 1 to 4 hours of reimplantation, we observed marked influx of polymorphonuclear leukocytes and lymphocytes and an increase in lectin-mediated cytotoxicity (25.6% +/- 14.8% and 50.6% +/- 20.1% versus 5.4% +/- 7.5% preoperatively; p < 0.05). In addition, natural killer cell cytotoxicity increased from 10.2% +/- 13.5% before transplantation to 20.5% +/- 8.6% 4 hours after transplantation (p < 0.03). By 24 hours MHC class II expression became evident and continued to increase while subtle histologic evidence of rejection appeared by 1 week. We conclude that ischemia-reperfusion injury can alter the local bronchopulmonary milieu, thus rendering it more susceptible to the development of rejection.

Animals↗

Effect of cardiopulmonary bypass on circulating lymphocyte function.

Extracorporeal cardiopulmonary bypass (CPB) has been associated with a wide variety of immunological derangements, including a transient postoperative impairment of lymphocyte function. We examined changes in phenotypic and nonspecific cytotoxicity of peripheral blood mononuclear cells after extracorporeal CPB. The peripheral blood samples obtained from 10 patients were subjected to natural killer and cytotoxic T lymphocyte activity assay before and at intervals after CPB. Phenotypic analysis of peripheral blood lymphocytes was performed in 5 patients before and immediately after CPB. We observed a significant increase in peripheral blood CD8+ cells (cytotoxic/suppressor T lymphocytes) (16.1% +/- 2.5% versus 22.5% +/- 2.1%; p less than .005) and a decrease in CD4+ cells (helper/inducer T lymphocytes) (46.1% +/- 3.5% versus 36.1% +/- 3.5%; p less than 0.02) immediately after extracorporeal circulation. The CD8/CD4 ratio in peripheral blood was significantly increased immediately after bypass (0.53 versus 0.80; p less than 0.001). No significant changes in percentages of other leukocyte subsets in peripheral blood were noted. The activity of cytotoxic T lymphocytes and natural killer cells in peripheral blood was impaired on postoperative days 1 and 3 but was restored to preoperative values by removal of mononuclear phagocytes from these cells. The decrease in natural killer cell and cytotoxic T lymphocyte activity in peripheral blood may signify a temporary impairment of the effector arm of the cell-mediated immunity in the post-operative period. The observed changes in peripheral blood phenotype and function may be involved in early organ injury and infectious complications after CPB.

Adult↗

Double-lung transplantation for cystic fibrosis. The Cystic Fibrosis Transplant Study Group.

One hundred twenty cystic fibrosis patients were accepted for transplantation. Twenty-five patients underwent double-lung transplantation. Twenty-five patients died awaiting transplantation (20.6%). There were 13 female and 12 male patients. Their mean age was 28 years (range, 7 to 34 years), and mean percentage ideal body weight was 76% (range, 58.5% to 91.9%). Most patients were hypoxic and hypercarbic. Two patients underwent tracheal anastomosis, 15 had en bloc bronchial anastomoses, and 8 had sequential single-lung transplants. Operative mortality was 16%; all deaths were related to bleeding from extensive adhesions. Actuarial survival at 1 year was 64%. Rejection and infection were frequent during the first month and decreased thereafter. Airway complications occurred in 5 patients but were amenable to laser therapy and stenting. We conclude that double-lung transplantation is an acceptable modality for the treatment of cystic fibrosis patients with end-stage lung disease. It may be a better alternative to heart-lung transplantation considering the paucity of thoracic organ donors.

Adolescent↗

Current status of lung transplantation for cystic fibrosis.

Lung transplantation has emerged as an acceptable option for the management of cystic fibrosis patients with endstage lung disease. Heart-lung transplantation and, more recently, double lung transplantation have been successfully performed in this group of patients. The choice of operation, so far, has been based on the surgeon's preference and experience as well as the cardiac function of the patient. Each of the procedures has advantages and disadvantages. This article reviews the current worldwide experience in lung transplantation for patients with cystic fibrosis and highlights the controversies involved in the selection of patients and procedure.

Contraindications↗

Phenotypic expression of bronchoalveolar lavage cells in lung rejection and infection.

The differentiation of episodes of lung allograft rejection from infection continues to be a problem. Bronchoalveolar lavage (BAL) has recently gained some success in the diagnosis and management of interstitial lung disease. To assess the usefulness of BAL in differentiating between lung allograft rejection and infection, we examined the differences in cellular subsets of BAL and peripheral blood (PBL) samples in a controlled canine model of rejection or pneumonia. Single-lung allotransplants were allowed to undergo rejection by withdrawing immunosuppressive agents (n = 6). In another group of dogs (n = 5), pneumonia was induced by transbronchial injection of Pseudomonas aeruginosa and melted agar followed by bronchial fulguration. Cells obtained from bronchoscopic BAL and PBL samples were labeled with functionally characterized cross-reactive murine monoclonal antibodies. Transthoracic needle biopsies and transbronchial biopsies were done to assess their adequacy in examining the rejecting or infected lungs and were compared with open lung biopsies. We found the following: (1) the percentage of DT2-labeled cells was significantly higher (p less than 0.05) in BAL samples from rejecting lungs compared with infected lungs; (2) the PBL/BAL ratio of DT2-labeled cell percentages was significantly higher in pneumonia (1.7 +/- 0.3) than rejection (0.5 +/- 0.2) (p less than 0.004); (3) the percentage of E11-labeled cells in PBL samples was significantly higher (p less than 0.02) in rejection than in infection; and (4) the ratio of WIG4 to DT2 cellular subset percentages in BAL samples from rejection (26.8 +/- 9.9) was significantly lower than from infection (61.0 +/- 22.9) (p less than 0.03). Transthoracic and transbronchial biopsies did not always yield representative specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Altered cellular immune function in the atelectatic lung.

Pulmonary atelectasis is common and may predispose the lung to infection. We have previously shown that atelectasis impairs alveolar macrophage antibacterial function. This study examines the effect of atelectasis on the cytotoxic function of lymphocytes harvested from the bronchoalveolar space of atelectatic lung segments by bronchoalveolar lavage. Specifically, we studied natural killer and lectin-dependent cell-mediated cytotoxicity in peripheral blood and bronchoalveolar lavage lymphocytes from the atelectatic lower lobes and contralateral normal lobes in a group of 8 dogs. We observed a decline of natural killer and lectin-dependent cell-mediated cytotoxicity to 62.7% and 61.5%, respectively, of preatelectasis control values in the affected lung lobes (p less than 0.01). Simultaneous measurements of cytotoxic activity of bronchoalveolar lavage lymphocytes harvested from the unaffected contralateral normal lungs were comparable with control values. On the other hand, natural killer and lectin-dependent cell-mediated cytotoxicity activities in peripheral blood lymphocytes were significantly increased in animals having right lower lobe atelectasis (166.7% and 154.7% of pretreated normal control, respectively, p less than 0.01). Atelectasis was also associated with an influx of polymorphonuclear leukocytes into the bronchoalveolar compartment. These findings confirm the presence of natural killer cells and cytotoxic lymphocytes in the bronchoalveolar compartment and demonstrate an atelectasis-induced impairment of local bronchoalveolar lymphocyte function. Such a dysfunction of local lung cellular host defenses may render the atelectatic lung susceptible to infection.

Animals↗

Bronchoalveolar lavage in lung transplantation.

One of the dilemmas in the management of lung allotransplant recipients is our inability to precisely determine the cause of graft dysfunction. Differentiating between lung allograft infection, rejection, atelectasis, or ischemic injury remains a difficult task. Tests directed at identifying systemic abnormalities such as peripheral blood analysis so far have been nonspecific and unlikely to accurately and promptly represent changes occurring within the lungs. Transbronchial biopsy and bronchoalveolar lavage have emerged as two methods with the most potential for aiding in the establishment of diagnosis. This review attempts to provide the readers with a current knowledge of the cellular events in lung allograft and the status of bronchoalveolar lavage in experimental and clinical lung transplantation.

Bronchoalveolar Lavage Fluid↗

Hemodynamic effects of lobar pulmonary artery occlusion in a porcine sepsis model.

We induced severe pulmonary hypertension and acute lung injury in 6 pigs by Pseudomonas aeruginosa infusion. We studied the effect of pulmonary artery catheter inflation of a pulmonary artery catheter balloon in the left lower lobar pulmonary artery was accompanied by a significant (p less than 0.05, paired t test) increase in pulmonary artery pressure, a decrease in left atrial pressure, a decrease in cardiac output, and a decrease in mean arterial pressure. No significant changes occurred when the catheter was advanced into the wedged position without balloon inflation. Balloon inflation had no significant effect on these variables before bacterial infusion. We conclude that with sufficiently severe pulmonary hypertension in association with diffuse lung injury, lobar pulmonary artery occlusion may cause alterations in cardiac output and left atrial pressure. This may confuse interpretation of pulmonary artery catheter measurements.

Animals↗

Successful treatment of steroid-resistant double-lung allograft rejection with Orthoclone OKT3.

An 18-yr-old woman with cystic fibrosis who received a double-lung transplant developed a severe episode of acute lung rejection. Bronchoalveolar lavage and transbronchial biopsy were used to establish the diagnosis. The rejection was refractory to administration of high-dose pulse steroids. OKT3 therapy was successfully used to reverse this episode. This is the first case report of a steroid-resistant double-lung allograft rejection successfully treated with OKT3.

Adolescent↗

The reversibility of impaired mucociliary function after lung transplantation.

Impairment of mucociliary function occurs after lung transplantation and may predispose patients to repeated pulmonary infections. The purpose of this study is to determine whether and how soon such mucociliary function may recover. Ten dogs underwent left lung autotransplantation. Within 3 weeks five of these dogs underwent study for proximal airway clearance by observation through a bronchoscope of the movement of carbon particles placed at different locations on the tracheobronchial mucosa. The mechanical properties of collected mucus from specific sites were determined by magnetic rheometry. The right lung, which was not operated on, served as a paired control. Similar studies were conducted in the remaining five dogs at 12 weeks after autotransplantation. Lung autotransplantation caused significant depression of proximal airway clearance and a 35% increase in mucous rigidity (p = 0.05) soon after operation. At 12 weeks after operation, there was a partial recovery of proximal airway clearance. Mucous changes were no longer consistent. Histologic and electron microscopic examinations initially revealed focal denudation of ciliated cells and loss of the bronchial glands. At 12 weeks there was a regeneration of cilia and a reappearance of the bronchial glands. We conclude that the mucociliary function, observed to be depressed early after lung autotransplantation, recovers partially during the late postoperative period. Thus the mucociliary functional recovery should be attributed to revascularization rather than to reinnervation, since the latter is unlikely to occur during this period.

Anastomosis, Surgical↗

Warm ischemia induces alteration in lung immune cell functions.

Warm ischemia is an important factor in early allograft dysfunction. To elucidate cellular events involved in such lung injury, we examined the effects of warm ischemia on the cytotoxic function of lymphocytes retrieved by bronchoalveolar lavage as compared with peripheral blood lymphocytes. Warm ischemia of the lung was induced in eight dogs by crossclamping left hilar structures for 1 hour. Bronchoalveolar cells from ischemia left and unaffected right lungs, as well as blood lymphocytes, were isolated before operation and 2 hours, 72 hours, and 7 days after operation. Lung and blood lymphocytes were assayed for natural killer and lectin-dependent cell-mediated cytotoxicity. Warm ischemia resulted in a significant impairment of natural killer activity within 2 hours of reperfusion (49% of preoperative control cytolysis, p less than 0.01). There was a significant increase in natural killer activity in bronchoalveolar lavage mononuclear cells 72 hours after reperfusion injury (178.4% of preoperative value, p less than 0.01). Interestingly, these functional alterations were not paralleled with changes seen in the peripheral blood lymphocytes or the opposite nonaffected lungs, where the natural killer activity appeared significantly depressed at 72 hours. Similarly, lectin-dependent cell-mediated cytotoxicity was noted to be increased in the bronchoalveolar lavage from the ischemic lung (179.5%, p less than 0.01) but decreased in the bronchoalveolar lavage from the nonaffected lung and peripheral blood lymphocytes at 72 hours after injury. We conclude that warm ischemia is associated with a functional alteration of the local lung immune cells. Such alteration is not observed in cells from the opposite lung or peripheral blood. The observed increase in nonspecific cytotoxicity of bronchoalveolar lymphocytes can be causative in the early damage seen in poorly preserved lung allografts.

Animals↗