Comparison of the Raja and the Abrams pleural biopsy needles in patients with pleural effusion.

In 31 patients with exudative pleural effusions, we compared the diagnostic yield of the Abrams pleural biopsy needle with that of a new instrument, the Raja pleural biopsy needle. Each patient was randomly biopsied with both needles, and a total of 153 pleural biopsies were done, 73 with the Abrams needle and 80 with the Raja needle. No complications resulted from biopsies with either needle. Etiologic diagnoses were possible in 38 (52%) biopsies obtained using the Abrams needle, compared with 66 (82.5%) for those using the Raja needle; the difference in proportions for the diagnostic yield was statistically significant (p < 0.01, two-tailed Fisher's exact test). There were no significant differences between the needles in obtaining etiologic diagnoses in any specific disease category. The difference between the mean size of the pleural specimens obtained with the two needles was also statistically significant (p < 0.001, Mann-Whitney U test). The Raja pleural biopsy needle is easy and safe to use, and despite its smaller external diameter yields a significantly larger pleural tissue sample and significantly increases the diagnostic yield of pleural biopsies compared with the Abrams pleural biopsy needle.

Cyclosporine-induced tolerance in experimental organ transplantation. Evidence of diminished donor-specific cytotoxicity relative to donor-specific proliferative response.

Alloreactivity of intragraft and peripheral blood lymphocytes from tolerant canine lung allograft recipients was examined. Tolerance was induced by variable periods of treatment with cyclosporine. Analysis of effector cells from lung allografts (obtained by bronchoalveolar lavage) revealed the absence of specific cytolytic T lymphocyte (CTL) activity and the presence of a low level of cytolytic activity detected in a lectin-dependent cell-mediated cytotoxicity assay. In contrast, high levels of specific CTL activity and lectin-dependent activity were detected in cell preparations from lung allografts undergoing rejection. Tolerant recipients retained normal ability to generate specific CTL activity to third party alloantigens in mixed lymphocyte cultures (MLC) but had diminished ability to generate CTL to donor alloantigens in recipient X donor MLC. Addition of exogenous interleukin 2 to these MLC was unable to restore donor-specific CTL activity. Lymphocytes from tolerant recipients were, however, capable of generating proliferative responses and lectin-dependent cytotoxicity on exposure to donor alloantigens in MLC. Evidence presented in this report suggests that the lectin-dependent cytolytic activity generated in these MLC is mediated by lymphokine-activated killer cells. Such cells are likely to be activated by interleukin 2 released in the proliferative response. The results support the proposal that the cyclosporine-induced tolerant state is characterized by the relative inability to respond against major histocompatibility complex class I antigens in contrast to class II antigens and/or minor histocompatibility antigens since MLC-induced CTL are directed, for the most part, against class I molecules.

Concanavalin A-dependent cell-mediated cytotoxicity in bronchoalveolar lavage fluid. Correlation with lung allograft rejection in mongrel dogs during cyclosporine dose tapering.

Although cyclosporine (CsA) is widely used as the primary agent for inhibiting the rejection of organ allografts in man, the ideal immunosuppressive regimen for utilizing this drug is still uncertain. To investigate this question, a concanavalin A (con A)-dependent cell-mediated cytotoxicity (CDCMC) assay was used to examine the development of intragraft and peripheral blood cytolytic T lymphocyte activity during CsA dose tapering. These studies were conducted in a canine single-lung transplantation model that facilitates serial examination of intragraft effector cells by bronchoalveolar lavage (BAL). A remarkable correlation of increased intragraft CDCMC and clinical evidence of lung allograft rejection was observed during CsA dose tapering in some recipients. In other recipients CDCMC remained low and evidence of rejection was not observed during drug tapering. In contrast, peripheral blood CDCMC did not correlate well with evidence of rejection. Rejection phenomena observed after termination of CsA therapy were reversed by resumption of CsA treatment but were not reversed by administration of methylprednisolone. Furthermore, the increased level of CDCMC was diminished by reinstitution of CsA therapy at the initial dosage. Following termination of CsA therapy, a prolonged period of unresponsiveness was observed in nearly two-thirds of the recipients, and 60% of these latter dogs had unlimited survival of their lung allografts (median greater than 496 days). Intragraft CDCMC remained low during the periods of unresponsiveness and increased upon onset of rejection. We conclude that measurement of intragraft CDCMC is a useful in vitro method of monitoring lung allograft rejection, and therefore provides a technique for adjusting CsA dosage schedules to achieve maximally effective immunosuppression. The use of this assay for monitoring rejection of other organ grafts requires further investigation.

Bronchial anastomotic healing in canine lung allotransplants treated with cyclosporine.

Bronchial anastomotic healing was evaluated in 22 long-term-surviving canine lung allotransplant recipients treated with cyclosporine as the major immunosuppressive agent. Mean survival in these dogs was over 155 days, and 4 animals survived 1-3 years. Bronchial anastomotic complications were limited to 5 cases of minimal (less than 15%) bronchostenosis. The bronchial anastomoses became somewhat edematous and friable during rejection episodes, but no clinically serious sequelae--such as hemorrhage, peribronchial abscess, or bronchial dehiscence--were observed. Gross and microscopic evaluation of the recipient and donor segments of the anastomoses revealed excellent healing, with only scattered areas of inflammatory cells. The decreased frequency and severity of rejection episodes in animals treated with cyclosporine permits early revascularization of the bronchus to take place and reduces the need for other immunosuppressive agents that may interfere with bronchial healing. Cyclosporine is an effective immunosuppressive agent for canine lung allotransplantation and allows normal bronchial anastomotic healing to occur.

Influence of bronchial circulation and corticosteroid therapy on bronchial anastomotic healing.

In order to assess the effect of revascularization on the healing of bronchial anastomoses in a canine model, we developed a microsurgical technique that permits the immediate reperfusion of the distal bronchial segment by a direct anastomosis of the bronchial artery to an intercostal artery. This technique was applied to dogs that underwent hilar stripping and bronchial transection and reanastomosis, and it prevented the development of ischemic bronchial damage. In addition, several groups of dogs that had undergone bronchial transection and reanastomosis and, in some cases, reestablishment of bronchial arterial circulation, were treated with 40 mg of prednisone daily for periods of 7 and 21 days. The animals treated with corticosteroids demonstrated a lesser degree of inflammatory damage to the bronchial anastomotic site than similar groups of untreated animals. These findings support the hypothesis that restoration of bronchial arterial blood flow at the time of lung transplantation can reduce anastomotic damage to the distal or donor bronchial component. Our results further suggest that corticosteroid therapy alone does not increase bronchial anastomotic damage, and, in fact, may reduce inflammation at the bronchial anastomotic site.

Single lung transplantation with cyclosporin immunosuppression. Evaluation of canine and human recipients.

Cyclosporin, a potent new immunosuppressive agent, was used (alone or in combination with other drugs) in 28 canine single lung allograft recipients. Mean recipient survival with good allograft function was 155 days with cyclosporin and far exceeded that obtained in previous single lung allograft recipients treated with standard immunosuppression (15 to 22 days). The results of these experiments were as follows: (1) 20% of the recipient animals exhibited no evidence of rejection whatsoever; (2) four of 28 animals survived more than 350 days with good allograft function; (3) 79% of the animals exhibited some evidence of rejection that was easily reversed in 74% of instances with corticosteroids; (4) 10 of 28 animals exhibited good lung allograft function 5 months or more after operation; (5) in cyclosporin-treated lung allograft recipients, rejection was diagnosed by the presence of infiltrate on chest roentgenogram, analysis of the cellular content of bronchoalveolar lavage samples, and decreased perfusion on 99mtechnetium lung scan; (6) complete healing without stenosis of the bronchial anastomosis occurred in 82% of the animals studied. One of two patients treated with cyclosporin after undergoing single lung allografting survived 7 weeks after transplantation and 4 weeks after contralateral pneumonectomy. Episodes of rejection were reversible, and the bronchial anastomosis healed normally. This overall experience indicates that cyclosporin, although not a perfect immunosuppressive agent, increases the likelihood of success with therapeutic single lung transplantation.

Cyclosporin A in experimental lung transplantation.

Cyclosporin A (Cy A) has been used in combination with low-dose azathioprine (2 mg/kg/day for 14 days) or other immunosuppressives to treat 13 canine lung allograft recipients. Two of five dogs treated with Cy A and azathioprine survive at 13 and 6 months, respectively, with normal lung function and no evident rejection. The other three dogs in this group survived for over 5 months despite evidence of rejection which was reversed with methylprednisolone (50 mg/kg/day for 3 to 5 days). The addition of prophylactic corticosteroids or their substitution for azathioprine resulted in decreased survival without preventing rejection better. The lung allograft rejection that occurred with Cy A was usually later in onset and more easily reversed by corticosteroids than the lung rejection that occurred with standard immunosuppression. Cy A rejection was also sometimes qualitatively different. Perivascular mononuclear cell cuffs and a proportionally greater decrease in allograft perfusion with respect to ventilation were often more prominent than in rejection with standard immunosuppression. In some instances, decreased allograft perfusion evidenced rejection while the plain chest roentgenogram and ventilation remained normal. Except for infection, which only occurred in animals receiving prophylactic corticosteroids, there was no toxicity from Cy A. These findings indicate that this drug is the safest, most effective immunosuppressive agent yet available for use in lung transplantation.

Usual interstitial pneumonia following Texas A2 influenza infection.

In two patients a documented Texas A2 influenza infection was associated with the development of interstitial pulmonary disease. One patient had an acute fulminating process resulting in respiratory failure and necessitating ventilatory assistance. Open lung biopsy revealed a histologic picture consistent with usual interstitial pneumonia (UIP). The other patient had a subacute course, and the pulmonary histology showed UIP with features of desquamative interstitial pneumonia. The influenza virus may have had an etiologic role in the development of the interstitial lung disease in our two patients.

Cell content in repetitive canine bronchoalveolar lavage.

To determine the effects and effectiveness of small volume (50 ml) bronchoalveolar lavage, lavages were performed on healthy mongrel dogs under a number of protocols. The differential and total cell counts in small volume bronchoalveolar lavages were determined. These factors were compared to those obtained by large volume (500 to 600 ml) lavage of the same segment in a second experimental group. Small volume lavage yielded a greater total cell count per milliliter and a greater concentration of polymorphonuclear leukocytes (PMNs) than large volume lavage, in which there was a somewhat higher concentration of bronchial cells. We compared the cell populations from lobes lavaged at 48-hour intervals. No significant changes in these populations or in pulmonary histology were noted. Our results suggest that small volume bronchoalveolar lavage provides a representative sample of the total free cell yield from the lower respiratory tract. Furthermore, small volume bronchoalveolar lavage performed at 48-hour intervals does not influence the distribution of these cells or significantly damage the pulmonary parenchyma.

Actinomycotic cervical abscess: A complication of transtracheal aspiration.

Transtracheal aspiration is frequently employed to obtain sputum for microbiologic analysis. Infectious complications of this procedure have been reported rarely. We report an actinomycotic anterior cervical abscess traversing the needle track of a transtracheal aspiration in a patient with actinomycotic pneumonia. Organisms most frequently encountered in anterior cervical abscesses complicating transtracheal aspiration have the recognized potential for local invasion of soft tissue from the primary pulmonary lesion.