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Biomedical subjects

E R Garrity

Publications and source records attributed to E R Garrity.

At least 37 records · Page 2Linked to original sources
PubMed1996

Molecular analysis of human cytomegalovirus strains from two lung transplant recipients with the same donor.

A total of four cytomegalovirus (CMV) isolates were obtained from two CMV seronegative patients, each of whom received a lung transplant from the same seropositive donor. CMV was isolated from Patient 1 from two bronchial alveolar lavage (BAL) specimens, one obtained during treatment with ganciclovir (GCV) and a second during later treatment with foscarnet. Both of these isolates are sensitive to GCV and foscarnet. CMV was isolated from Patient 2 from a blood and a BAL specimen obtained during treatment with GCV. Both of these isolates are resistant to GCV and show reduced GCV phosphorylation. Patient 1 is still alive 33 months posttransplant. Patient 2 died 6 1/2 months posttransplant. Although the four strains differ with respect to GCV susceptibility and phosphorylation, their DNA restriction fragment hybridization patterns and UL97 kinase gene sequences indicate that they are closely related. The restriction fragment hybridization patterns are identical among the strains, while these patterns differ markedly from those of unrelated strains. The DNA sequences of the UL97 genes of the strains from Patient 2 differ by only one nucleotide from those of Patient 1. The same comparison with unrelated strains shows a minimum of 12 nucleotide differences. The nucleotide change in the strains from Patient 2 produces an amino acid substitution of serine for leucine at residue 595, a substitution that was previously shown to transfer GCV resistance. Both patients, therefore, were apparently infected with the same donor strain, but during the course of GCV prophylaxis and treatment, a GCV-resistant mutant strain was selected in Patient 2.

Base Sequence↗
PubMed1996

Bronchiolitis obliterans organizing pneumonia-like reactions: a nonspecific response or an atypical form of rejection or infection in lung allograft recipients?

Bronchiolitis obliterans organizing pneumonia (BOOP) is a ubiquitous entity, known to occur either idiopathically or in association with various pulmonary disorders. Histologically, it is characterized by myxomatous connective tissue plugs present in the lumen of bronchioles with extension into the alveoli. Its significance in lung allograft recipients is not well documented. The authors reviewed all post-lung transplant biopsies (565 transbronchial; 19 open), explanted lungs for retransplantation (six), and autopsies (38) from 115 patients. A total of 32 patients (18 females and 14 males) showed histological evidence of BOOP-like reactions (ie, Masson bodies in 44 transbronchial and seven open lung biopsies). The mean age was 47 years (range = 14 to 69 years). Sixteen patients were recipients of single lungs, 14 received bilateral single lungs, and two had heart and double-lung transplants. BOOP-like reactions (BOOP-LRs) occurred as early as day 5 and as late as day 1,208 (40 months) posttransplantation. Twenty patients had one biopsy showing BOOP-LR, of which three patients had resolving mild acute rejection, four had ongoing minimal acute rejection, seven had ongoing mild acute rejection, one each had ongoing moderate and bronchiolar rejection, and four showed associated cytomegalovirus (CMV) pneumonitis. Seven patients had two biopsies each of BOOP-LR of which six were associated with ongoing minimal or mild acute rejection, and one had resolving mild acute rejection. Three patients had three biopsies each of BOOP-LR all associated with ongoing minimal or mild acute rejection. Two patients had four biopsies each, showing BOOP-LR, with ongoing mild or moderate acute rejection or CMV pneumonitis. Forty of the total 115 lung transplant patients (34.8%) have developed bronchiolitis obliterans syndrome (BOS) or chronic airway rejection. Twelve of these patients are from the study group, of which five have a biopsy proven histological diagnosis of obliterative bronchiolitis (OB), and the remaining seven patients have been diagnosed clinically by deteriorating lung function tests. The authors conclude that BOOP-LR in the lung transplant setting result from acute epithelial injury secondary to either allograft rejection or an ongoing infection and are not a component of, nor do they necessarily predispose to, chronic rejection.

Acute Disease↗
PubMed1996

Post-lung transplant biopsies: an 8-year Loyola experience.

A total of 125 transplant procedures involving the lung have been performed at Loyola University of Chicago in 120 patients. There were 67 single (40 right, 27 left), 44 bilateral single, 2 double lung, and 12 heart-lungs (HL) transplant procedures. This paper summarizes the pathologic findings in 565 transbronchial, 102 endobronchial, 20 open lung, and 92 endomyocardial biopsies and compares them with the recommendations in the published literature. The lung biopsies were evaluated according to the Working Formulation, Lung Rejection Study Group, International Society of Heart Transplantation. In transbronchial biopsies, all of which were from the transplanted lungs, the number of alveolated lung fragments ranged from 0 to 14 (mean, 5). Two hundred twelve biopsies showed no rejection, 113 had minimal rejection, 133 had mild rejection, 34 had moderate rejection, and 1 had severe acute rejection. Active airway damage (Grade B) was seen in 48 biopsies, which were graded from minimal to severe based on the amount of inflammation. Chronic rejection (Grade C) was diagnosed in 23, chronic vascular rejection (Grade D) in 8, and acute vasculitis (Grade E) in 9 biopsies. Routine trichrome and elastic van Gieson stains did not add to the diagnosis. All biopsies were routinely stained with immunoperoxidase for cytomegalovirus. Cytomegalovirus was diagnosed in 84 biopsies, 54 by both H&E and immunoperoxidase, 23 by immunoperoxidase alone, and 5 by H&E alone. The endobronchial biopsy of the anastomotic site had nonspecific inflammation in 46 biopsies. Twenty-nine had infection with a specific organism, Aspergillus and Candida in each of 8 biopsies by Gomori's methenamine silver stain, cytomegalovirus in 7 (4 by H&E and immunoperoxidase; 3 by immunoperoxidase), bacteria in 4, and fungal hyphae in 2 biopsies. In the 12 patients with heart-lung transplants, a total of 92 endomyocardial, 35 transbronchial, and 1 endobronchial biopsies were obtained. Acute rejection was seen only in 2 endomyocardial biopsies, whereas the transbronchial biopsy showed acute mild or moderate rejection in 10, chronic rejection in 1, and cytomegalovirus infection in six biopsies. We conclude that: (a) all biopsies with alveolated lung parenchyma can be evaluated for rejection and infection yielding clinically significant diagnoses; (b) sections from three levels stained by H&E are essential for evaluation; (c) routine Gomori's methenamine silver, elastic van Gieson, and trichrome stains are not required for transbronchial biopsy, however, routine Gomori's methenamine stain is recommended for all anastomotic site biopsies; (d) routine immunoperoxidase for cytomegalovirus is extremely helpful; (e) Grade B rejection should be further graded; and (f) endomyocardial biopsy played no significant role in the management of heart-lung recipients.

Acute Disease↗
PubMed1996

Bronchiolar basement membrane changes associated with bronchiolitis obliterans in lung allografts: a retrospective study of serial transbronchial biopsies with immunohistochemistry [corrected].

Lung transplantation is an accepted mode of therapy for selected patients with end-stage lung disease. Their long-term survival is mainly limited by chronic rejection, i.e., bronchiolitis obliterans (BO), which represents a fibrosing inflammatory process of the terminal and respiratory bronchioles, leading to progressive small airway obstruction. To evaluate its development, and associated irreversible allograft dysfunction, we retrospectively studied the histological and clinical data from nine patients who developed BO, and nine matched control patients. A total of 152 serial transbronchial biopsies (87 from patients with BO; 65 from the control group) were studied using immunohistochemical stains, with antibodies to laminin, desmin, fibronectin, collagen IV, collagen III, and vimentin. The staining with anti-collagen IV antibody was the most productive and in eight of the nine patients with BO demonstrated early focal bronchiolar basement membrane damage, manifested by thickening and subsequent splitting and duplication. This was seen in association with the second episode and onward of clinically significant episodes of acute cellular rejection which occurred 7 to 12 months posttransplant. The larger airways were unaffected. The histological onset of BO exhibited varying degrees of obstruction of the bronchioles with no detectable basement membrane staining. The control patients failed to demonstrate these findings. The other immunohistochemical stains used were found to be noncontributory. We conclude that the usage of anti-collagen IV on lung allograft biopsies demonstrates the sequential changes of bronchiolar basement membrane disruption in lung allograft recipients who have multiple episodes of clinically significant acute cellular rejection and later develop BO.

Adolescent↗
PubMed1996

Postmortem findings in lung transplant recipients.

Lung transplantation is now an accepted modality for treating end-stage lung disease. To better understand the factors limiting the survival of these patients, we reviewed the autopsy findings in 37 patients who received lung transplants. Between 1986 and 1995, 131 patients have undergone lung transplantation at our institution, including 4 patients with repeat transplantations. Of these, 48 (36.6%) died, 37 (77%) of whom had an autopsy. The autopsied patients were divided into three groups on the basis of post-transplantation interval: early (< 30 d), intermediate (31-365 d), and late (> 365 d). Of the 12 patients in the early group, 6 died of intra- and postoperative complications and 6 of bacterial infection with pneumonia in the transplanted lung. There were 18 patients in the intermediate group, of whom 11 died of infection (5 of cytomegalovirus, 5 of nonviral infections of the transplanted lung, and 1 of encephalomyelitis), 3 of post-transplantation lymphoproliferative disorder, 3 of chronic airway rejection, and one of unrelated cause. Of the seven patients in the late group, four died of chronic airway rejection, two of unrelated causes, and one of bacterial infection. Native lungs examined in 23 patients showed, in addition to the primary disease, bacterial pneumonia in 5, post-transplantation lymphoproliferative disorder in 3, cytomegalovirus in 2, and aspergillosis in 1. In this series of 37 autopsied patients, chronic rejection was the cause of death in 7 and was concomitantly seen in 3 patients (27%). In summary, the most common cause of death was infection (48%), followed by chronic rejection (19%), surgical complications (19%), post-transplantation lymphoproliferative disorder (7%), and unrelated causes (7%); rejection was not a major cause of death in the early and intermediate post-transplantation periods; in 30% of native lungs, significant pathologic findings were present in addition to the primary disease; and in the intermediate post-transplantation period, significant left ventricular hypertrophy occurred, which may be attributable to cyclosporine-induced hypertension but which needs to be further studied.

Adolescent↗
PubMed1996

Lung transplant rejection: obliterative bronchiolitis.

BACKGROUND: More centers are performing lung transplants for a variety of pulmonary conditions. Chronic rejection, manifested as obliterative bronchiolitis, is the most common cause of late death (greater than 6 months after transplant) in this population. OBJECTIVES: To review published literature on obliterative bronchiolitis to determine the current terminology and definition, pathophysiology, incidence, diagnosis, treatment, and outcome of this condition. DATA SELECTION: A MEDLINE search was done using the medical subject headings of bronchiolitis obliterans and lung transplantation. Studies were selected based on sample size and reporting of obliterative bronchiolitis statistics. Sources that were not data-based discussions also were selected if they were comprehensive reviews or provided insight into relevant issues. SUMMARY: Obliterative bronchiolitis terminology is not used consistently in the literature. It is an obstructive defect that affects the airways, causing progressive occlusion. Diagnosis is based on clinical findings or on histological analysis; early markers are sought, to aid in diagnosis. Incidence of obliterative bronchiolitis varies from 7% to 54%, with a mortality rate of 30% to 40%. Currently, enhanced immunosuppression is the treatment of choice, although research is being carried out to evaluate methods of inhibiting growth factor activity for use in future treatment strategies. CONCLUSIONS: Obliterative bronchiolitis is a common complication in lung transplant recipients, and future research will focus on treatment and early diagnosis. Efforts are under way to standardize nomenclature and reporting of incidence and mortality rates.

Bronchiolitis Obliterans↗
PubMed1996

Humoral (antibody-mediated) rejection in lung transplantation.

To confirm the existence and characterize the pathologic features of humoral (antibody-mediated) lung rejection, we prospectively studied 55 lung transplant recipients (24 male [44%] and 31 female [56%], age range 14 to 69 years [mean 45]). The time between transplantation and biopsy ranged from 2 to 1546 days (mean 274). We performed direct immunofluorescence with C3, immunoglobulin M, and immunoglobulin G antibodies on frozen sections of 106 transbronchial biopsies and one wedge biopsy and compared the results with 13 explanted lungs, one donor lung, and two controls. The histologic diagnoses of these 107 biopsies included acute cellular rejection (62, 58% [minimal 23, mild 33, moderate 5, and severe 1]), chronic rejection (eight, 7%), chronic vascular rejection (two, 2%), acute vasculitis (five, 5%), cytomegalovirus pneumonitis (two, 2%), acute pneumonia (two, 2%), acute organizing pneumonia (two, 2%), diffuse alveolar damage (one, 1%), no evidence of rejection or infection (30, 28%), lipoid pneumonia (one, 1%), and inadequate for histologic diagnosis (one, 1%). Eighty-nine of 106 (84%) transbronchial biopsies, the wedge biopsy, and control lungs were satisfactory for direct immunofluorescence, because each contained alveolate lung parenchyma and arterioles or venules. There was no demonstrable immunofluorescence in the wall of the blood vessels or in the lung parenchyma in any case. We conclude that (1) transbronchial biopsies and wedge biopsies provide adequate material to evaluate humoral rejection, and (2) in spite of the large population studied, the satisfactory material obtained, and the wide range of histologic diagnoses, we could not demonstrate the occurrence of humoral rejection in the lung.

Adolescent↗
PubMed1995

Bronchoalveolar lavage fluid endotoxin elevation in human single lung transplant recipients during rejection.

Endotoxin has been implicated as an aetiological factor in liver transplant rejection and acute graft-versus-host disease. To investigate the role of endotoxin in human single lung transplant rejection we measured the level of endotoxin in bronchoalveolar lavage (BAL) fluid from six subjects at baseline and during rejection, which was defined histologically from transbronchial biopsy. Differential cell counts of BAL fluid cells, the levels of protein and albumin in BAL fluid, and serum albumin levels were also examined. BAL fluid albumin to serum ratio was calculated to evaluate alveolar-capillary leakage. A significant elevation of BAL fluid endotoxin with rejection compared with baseline was observed. Standardizing endotoxin levels to BAL fluid volume, protein, or albumin were all of similar significance. Examination of BAL fluid cell population revealed a significant elevation in the percentage of lymphocytes with rejection. No significant difference between BAL fluid protein levels, BAL fluid albumin levels. BAL fluid albumin to protein ratio, serum albumin levels, or BAL fluid albumin to serum albumin ratio was seen with rejection. We conclude that BAL fluid endotoxin levels increase during lung rejection, endotoxin levels can be accurately standardized to millilitres of BAL fluid, and abnormal alveolar-capillary leakage does not appear to account for the increased BAL fluid endotoxin.

Bronchoalveolar Lavage Fluid↗
PubMed1995

Reduced transplant lung volumes after single lung transplantation for chronic obstructive pulmonary disease.

Single lung transplantation is now an extremely successful option for the treatment of end-stage chronic obstructive pulmonary disease (COPD). This procedure involves placing a normal sized lung in a hyperinflated hemithorax. Preliminary observations of these patients suggest that the transplanted lung volume is smaller than expected and often the native (COPD) lung increases in volume. The purpose of this investigation was to quantify the volume contributions of the transplant and native lung to the total lung capacity. In seven patients who underwent single lung transplant for end-stage COPD the transplant and native lung volumes were measured by computer-analyzed planimetry immediately after transplant and the following 6 mo post-transplant. The transplant lung volume was smaller than predicted immediately after transplant at only 33 +/- 5% (mean +/- SD) of predicted TLC. This did not change significantly over the next 6 mo. Native lung volume increased following transplant to 74 +/- 19% predicted TLC at 1 mo and 80 +/- 16% at 6 mo. Five of the seven patients subsequently underwent measurement of pleural pressures at TLC. The mean static pleural pressure at TLC was low at -16 +/- 5.1 cm H2O. In summary, following single lung transplantation for COPD the transplanted lung is significantly restricted. We conclude that the likely mechanism of this restriction is due to low transpulmonary pressure generation.

Female↗
PubMed1995

Early diagnosis of cytomegalovirus pneumonitis in lung transplant patients.

Cytomegalovirus (CMV) pneumonitis is an important cause of morbidity and mortality in lung transplant patients and requires timely and accurate diagnosis. This study compares the diagnostic utility of the evaluation of transbronchial biopsy by histology, immunohistochemistry, and simultaneous culture of bronchoalveolar lavage in a population of 13 lung transplant patients who underwent 78 biopsies during a period of 27 months. Our study concludes that, in patients clinically symptomatic for CMV pneumonitis, histology alone is diagnostic for the presence of the virus, whereas culture of bronchoalveolar lavage fluid is not as helpful. In asymptomatic patients, however, immunohistochemistry utilizing monoclonal antibodies to immediate-early and early CMV nuclear antigens may indicate development of CMV pneumonitis before cytopathic changes are evident.

Adult↗
PubMed1993

The Loyola University lung transplant experience.

BACKGROUND: We reviewed our experience with isolated lung transplantation at Loyola University Medical Center, Maywood, Ill. From April 1990 through June 1992, 33 lung transplantations for end-stage pulmonary disease were performed (30 single lung, three bilateral single lung). Recipient diagnoses include chronic obstructive pulmonary disease, alpha 1-antiprotease deficiency, pulmonary fibrosis, primary pulmonary hypertension, Eisenmenger's syndrome, sarcoidosis, cystic fibrosis, bronchiectasis, and bronchiolitis obliterans. METHODS: For patients who underwent transplantation for end-stage obstructive airway disease, we retrospectively reviewed functional indexes before and after transplantation. In addition, the overall survival rate was determined. RESULTS: Successful transplantation resulted in a marked improvement in functional capacity. Single-lung transplantation for end-stage obstructive airway disease resulted in a threefold improvement in the 1-second forced expiratory volume, from 0.49 to 1.64 L. The actual survival for all isolated lung transplant recipients (including both single-lung and bilateral single-lung procedures) was 73%, with a 15% 30-day mortality. CONCLUSION: Isolated lung transplantation can significantly improve functional capacity as well as the quality of life in patients with end-stage lung disease.

Actuarial Analysis↗
PubMed1993

Common infections complicating lung transplantation.

Infections are the most common cause of early and late morbidity and mortality in lung transplant recipients. Viral infections, in particular, have been linked to acute rejection, chronic rejection, and development of lymphoproliferative diseases.

Diagnosis, Differential↗
PubMed1992

Bronchial dehiscence associated with a large broncholith in a lung transplant recipient.

A 63-year-old man who underwent single lung transplantation for advanced emphysema had a postoperative course complicated by asymptomatic bronchial dehiscence associated with a large broncholith. The stone eventually caused airway obstruction requiring partial fragmentation and incomplete extrication. We suggest that calcified nodes of significant size be removed at the time of surgery in the lung transplant recipient.

Bronchial Diseases↗
PubMed1985

Autonomic response characteristics of porcine airway smooth muscle in vivo.

We studied the autonomic response characteristics of airways in 65 swine in vivo. Tracheal smooth muscle response was measured isometrically in situ; bronchial response was measured simultaneously as change in airway resistance and dynamic compliance. To determine the optimal resting length at which maximal tracheal contraction was obtained, length-tension studies were generated in four animals using maximal electrical stimulation of the vagus nerves determined from stimulus-response characteristics in eight other swine. Pharmacological studies were performed in 25 animals to determine the relative potency and intrinsic activity of agonists (acetylcholine greater than histamine much greater than norepinephrine) causing contraction of trachea and bronchial airways. In 13 swine, the effects of autonomic stimulation were studied by intravenous administration of dimethylphenylpiperazinium (DMPP) after muscarinic blockade with 1.5 mg/kg iv atropine. Tracheal contraction caused by topical application of 3.4 X 10(-4) mol histamine (13.4 +/- 1.54 g/cm) was 96 +/- 7.2% blocked by 25 micrograms/kg iv DMPP in adrenal-intact animals; minimal relaxation was demonstrated in adrenalectomized animals, indicating absence of substantial sympathetic innervation to porcine trachea. Nonadrenergic innervation was not demonstrated. After beta-adrenergic blockade, sympathetic stimulation caused alpha-adrenergic contraction in bronchial airways but not in trachea. These data define the unique response characteristics of the airways of swine and demonstrate their utility for acute experimental study of airway responses in vivo.

Acetylcholine↗
PubMed1985

Sympathetic modulation of biochemical and physiological response to immune degranulation in canine bronchial airways in vivo.

The effect of sympathetic stimulation on bronchial smooth muscle contractile response after mast cell degranulation with Ascaris suum antigen was studied in 36 natively allergic dogs in situ. Bronchial smooth muscle response was measured isometrically in a single right middle lobe bronchus. A dose of antigen causing maximal release of mediator was administered to the bronchus through the bronchial arterial circulation. Serial plasma histamine concentrations were determined at 15-s intervals after intra-arterial (i.a.) administration of antigen. Samples of blood were obtained simultaneously from right heart and femoral artery, and arteriovenous difference (AVd) in histamine concentration across the bronchus was determined during mast cell degranulation. In nine dogs showing bronchial mast cell degranulation to antigen challenge, bronchial smooth muscle contraction was 22.3 +/- 2.95 g and the mean AVd in histamine concentration across the bronchus was 188 +/- 41.5 ng/ml. Six other dogs having muscarinic blockade with 0.75-1.0 mg/kg intravenous atropine were given i.a. antigen after 1 min of steady-state sympathetic stimulation with intravenous 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP). Sympathetic stimulation during Ascaris suum antigen challenge caused complete inhibition of bronchial smooth muscle contractile response to i.a. antigen (P less than 0.001), and a significant AVd in histamine concentration across the bronchus (9.8 +/- 16.0 ng/ml; P less than 0.01 vs. control) was not detected. Peak plasma histamine concentration in control dogs was 1,138 +/- 237 ng/ml vs. 310 +/- 135 ng/ml in animals receiving sympathetic stimulation (P less than 0.01). In four dogs undergoing systemic anaphylaxis to i.v. antigen, subsequent sympathetic stimulation with i.v. DMPP reduced bronchomotor tone to approximately 70% of base-line control. Exogenously induced sympathetic stimulation can substantially inhibit systemic mast cell degranulation to Ascaris suum antigen in allergic dogs. Maximal stimulation of the sympathetic nervous system causes substantial inhibition of respiratory mast cell secretion of histamine and bronchial smooth muscle contraction to circulating mediator.

Airway Resistance↗