Isolation of protein-tyrosine phosphatase-like member-a variant from cementum.

Cementum has been shown to contain unique polypeptides that participate in cell recruitment and differentiation during cementum formation. We report the isolation of a cDNA variant for protein-tyrosine phosphatase-like (proline instead of catalytic arginine) member-a (PTPLA) from cementum. A cementifying fibroma-derived λ-ZAP expression library was screened by panning with a monoclonal antibody to cementum attachment protein (CAP), and 1435 bp cDNA (gb AC093525.3) was isolated. This cDNA encodes a 140-amino-acid polypeptide, and its N-terminal 125 amino acids are identical to those of PTPLA. This isoform, designated as PTPLA-CAP, results from a read-through of the PTPLA exon 2 splice donor site, truncating after the second putative transmembrane domain. It contains 15 amino acids encoded within the intron between PTPLA exons 2 and 3, which replace the active site for PTPLA phosphatase activity. The recombinant protein, rhPTPLA-CAP, has Mr 19 kDa and cross-reacts with anti-CAP antibody. Anti-rhPTPLA-CAP antibody immunostained cementum cells, cementum, heart, and liver. Quantitative RT-PCR showed that PTPLA was expressed in all periodontal cells; however, PTPLA-CAP expression was limited to cementum cells. The rhPTPLA-CAP promoted gingival fibroblast attachment. We conclude that PTPLA-CAP is a splice variant of PTPLA, and that, in the periodontium, cementum and cementum cells express this variant.

Transjugular liver biopsy in 52 patients with an automated Trucut-type needle.

A three-year prospective study was conducted to assess the efficacy and safety of transjugular liver biopsy with a Trucut-type needle employing an automated device. Fifty-two consecutive patients (39 women and 13 men), ages 46.3+/-14.6 years, in whom percutaneous liver biopsy was contraindicated were included in the study. An 18-gauge transjugular hepatic needle with a 20-mm throw length, a cutting cannula at the distal end, and an automated trigger device on the proximal end was used. All procedures were performed under fluoroscopic control, and the following variables were assessed: (1) number of passes, (2) size and average number of the obtained fragments, (3) number of portal triads, and (4) adequacy of the specimen for histologic diagnosis. The procedure was successful in 49/52 patients, and all samples obtained were satisfactory for histologic analysis even when cirrhosis or bridging fibrosis were present. Mean biopsy specimen length was 1.7+/-0.88 cm; mean number of passes was 2.42+/-1.01, the mean number of biopsy fragments and portal triads per attempt were 2.5+/-1.01 and 6.24+/-3.18, respectively. No major complications were observed. Transjugular hepatic biopsy with this new cutting system is an effective and safe procedure in patients with contraindication for percutaneous liver biopsy.

[A case of elevated transaminases caused by congestive heart failure simulating chronic hepatitis]. / Un caso de transaminasas altas por insuficiencia cardiaca congestiva que simulan hepatitis crónica.

We report the case of a young man first seen by is in 1989 at the age of 20 years. The diagnoses of hypertrophic cardiomyopathy, Wolf-parkinson-White syndrome, congestive heart failure and pulmonary hypertension were made. One month later the patient had jaundice and hepatomegaly and a diagnosis of acute viral hepatitis A was established by laboratory findings. The ALT and AST levels were persistently elevated, seven times the normal mean, during six years. Two liver biopsies in 1991 and 1993 showed liver injury secondary to congestive heart failure (CHF) as the only abnormality. This case illustrates the importance of liver injury secondary to CHF as a cause of a marked and persistent increase of ALT and AST that resembles that of other liver diseases.

Aspergillus infection in single and double lung transplant recipients.

To investigate the clinical manifestations of Aspergillus infections in lung transplant recipients, we reviewed the mycology and autopsy reports of all double (DLT=93) and single (SLT=48) lung transplant recipients from November 1983 to May 1993. Positive Aspergillus cultures were identified in 22% of the recipients (DLT=21, SLT=10). Colonization alone was present in 19 recipients (DLT=16, SLT=3). Complicated Aspergillus infection included Aspergillus bronchitis (DLT=1, SLT=1), aspergilloma (SLT=2), pulmonary invasive aspergillosis (DLT=1, SLT=2), disseminated aspergillosis (DLT=1, SLT=2), empyema (DLT=1), and a retroperitoneal abscess (DLT=1). Symptoms were seen only in patients with complicated lung infections and CXR abnormalities began in the native lung of four SLT recipients. Twenty patients survived (DLT=17, SLT=3) and 11 died (DLT=4, SLT=7) of disseminated aspergillosis (SLT=2), pulmonary invasive disease (DLT=1), bronchiolitis obliterans (DLT=2, SLT=2, CMV pneumonitis (SLT=1), diffuse alveolar damage (SLT=2), and hyperacute rejection (DLT=1). Complicated infection and mortality were more common in SLTs than DLTs (P<0.05). We conclude that infection with Aspergillus is not infrequent in the lung transplantation population. Single lung recipients develop more complicated infection than double lung recipients after Aspergillus infection with native lung being a potential source of infection.

Pleural complications in lung transplant recipients.

Pleural complications occurred in 30 (22%) of 138 patients after 53 single and 91 double lung transplants between September 1986 and February 1993. These were defined for the purpose of this study as pneumothorax persisting beyond the first 14 postoperative days, recurrent pneumothorax, or any other pleural process that necessitated diagnostic or therapeutic intervention. Overall, a higher pleural complication rate was seen in double lung transplantation (25 of 30) than in single lung transplantation (5 of 30) with no differences noted in the frequency among preoperative diagnostic groups (p > 0.05). Pneumothorax was the most frequent complication, affecting 14 of 30 patients, with 6 of 14 cases occurring after transbronchial biopsy. All pneumothoraces in single (n = 4) and double lung transplantation (n = 10) resolved spontaneously or with chest tube thoracostomy. One patient required placement of a Clagett window after open lung biopsy and another required thoracotomy and pleural abrasion after transbronchial biopsy. Parapneumonic effusion was observed in 4 of 30 double lung transplantations with spontaneous resolution in all cases. Empyema affected 7 of 30 patients and occurred exclusively in the double lung transplant group. Sepsis developed in three of the patients with this complication and they subsequently died. The risk of empyema was independent of preoperative diagnosis (p > 0.05). Of interest, all patients with cystic fibrosis (n = 3) with complicating empyema had Pseudomonas cepacia in the pleural fluid. Other miscellaneous complications included subpleural hematoma, chylothorax, and hemothorax. The latter two necessitated thoracic duct and bronchial artery ligation, respectively. In summary, a significant proportion of lung transplant recipients will have pleural space complications. The vast majority of these will resolve spontaneously or with conservative procedures. These complications were not related to preoperative diagnosis nor associated with a significant prolongation of hospital stay (p > 0.05). Empyema is the only pleural space complication associated with increased patient mortality and, as such, is an important clinical marker for those at risk for sepsis and death.

Acute lung injury in lung allografts.

BACKGROUND: Acute alveolar injury is a pathologic description of a nonspecific response of the lung to an acute injury. It has been our experience that acute alveolar injury may be seen in transbronchial biopsy and open lung biopsy specimens from patients who have successfully undergone lung transplantation. Because no studies of the clinical significance of acute alveolar injury in lung transplant recipients are available in the literature, we reviewed the impact of this pathologic finding in patients who underwent transplantation in the Toronto Lung Transplant Program. METHODS: From November 1983 through December 1992, we retrospectively reviewed all transbronchial biopsies and open lung biopsies performed in lung transplant recipients. RESULTS: Of the 137 transplantations performed (53 single and 84 double) acute alveolar injury was observed in 21 single (34 of 173 transbronchial biopsy and 3 of 11 open lung biopsy) lung biopsy) and 22 double (38 of 415 transbronchial biopsy and 3 of 11 open lung biopsy) lung transplantations. We sought to explain this finding on the basis of the concurrent clinical scenario. Acute alveolar injury occurred most commonly in association with infection (52%) followed by postoperative period (19%) and acute (16%) rejection. Acute alveolar injury occurred as an isolated finding in 7% of patients. It occurred within the first 4 months after transplantation in 80% of cases. In 10 of 21 single lung transplantations and 12 of 22 double lung transplantations, acute alveolar injury was seen at least twice. However, no difference was found in mortality between such patients (6 of 10 single and 6 of 12 double lung transplantations) and patients with only one episode of acute alveolar injury. CONCLUSION: Acute alveolar injury is a relatively common finding in histologic specimens from patients with lung transplantation and is most commonly associated with infection.

Haemodynamic effects of continuous positive airway pressure in humans with normal and impaired left ventricular function.

1. Continuous positive airway pressure increases intrathoracic pressure, thereby decreasing left ventricular preload and afterload. We hypothesized that there would be a dose-related alteration in cardiac and stroke volume indices in response to continuous positive airway pressure in normal subjects and patients with congestive heart failure and that the direction of response among those with heart failure would be related to left ventricular preload. 2. Cardiac and stroke volume indices were measured at baseline and after 10 min of continuous positive airway pressure at both 5 and 10 cmH2O (0.5 and 0.99 kPa respectively) in 16 patients with heart failure and five control subjects with normal cardiac function. Among the eight patients with heart failure and elevated pulmonary capillary wedge pressure (> or = 12 mmHg) (> or = 1.6 kPa), cardiac index increased from 2.47 +/- 0.34 at baseline to 2.91 +/- 0.32 to 3.12 +/- 0.40 l min-1 m-2 (P < 0.025) while on 5 and 10 cm H2O of continuous positive airway pressure respectively. In the same patients stroke volume index increased from 27.8 +/- 3.9 to 33.9 +/- 4.2 to 36.8 +/- 5.5 ml/m2 (P < 0.05). In contrast, in both the control subjects and patients with heart failure and normal pulmonary capillary wedge pressure (< 12 mmHg) there was a dose-related decrease in cardiac and stroke volume indices while on continuous positive airway pressure. 3. Continuous positive airway pressure causes dose-related increases in cardiac and stroke volume indices among patients with chronic heart failure and elevated left ventricular filling pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Causes of death in lung transplant recipients.

Between November 1983 and September 1992, The Toronto Lung Transplant Program performed 131 lung transplantations in 122 recipients; 53 single lung transplantations and 78 double lung transplantations. Forty-five patients died, 25 (47%) in the single lung transplantation and 20 (25%) in the double lung transplantation groups. We retrospectively reviewed the hospital charts of all deceased recipients and the postmortem reports of the 35 patients (20 single lung transplantations and 15 double lung transplantations) who had autopsies. Preoperative single lung transplantation diagnoses included pulmonary fibrosis, (n = 17) obstructive disease (n = 6) and vascular disease (n = 2). Preoperative diagnosis of double lung transplantation included pulmonary fibrosis (n = 2), obstructive disease (n = 6), septic lung disease (n = 9), and vascular disease (n = 3). The most common cause of death in single lung transplantation was infection. Five patients died of bronchiolitis obliterans, and five more had bronchiolitis obliterans lesions present at autopsy that were not a direct cause of death. Diagnosis of primary disease was made in 23 of 25 single lung transplantations antemortem and 2 of 25 at autopsy. Autopsy diagnoses were disseminated Aspergillus and cytomegalovirus infection. In double lung transplantations, infection was also the primary cause of death; in three other patients, airway dehiscence preceded infection. Bronchiolitis obliterans was the second most common cause of death and was also present in four patients dying of infection. All double lung transplantation diagnoses were made antemortem. We concluded that infection and then bronchiolitis obliterans are the primary causes of death after lung transplantation. Although infection is a major cause both early and late after transplantation, bronchiolitis obliterans is an important factor in transplantation only late after the operation.

Pulmonary manifestations of coccidioidomycosis.

Pulmonary coccidioidomycosis is a fungal disease seen primarily in the southwestern United States and Mexico. However, with the advent of mass travel it is being seen increasingly in countries outside the zone where it is endemic. Pulmonary coccidioidomycosis, which has a high infectivity, is acquired by inhalation of fungal arthrospores. Its infectivity is increased in immunosuppressed patients, particularly those with the acquired immunodeficiency syndrome. Because of these factors, it is important for radiologists (particularly those practising outside the area of endemicity) to recognize the various manifestations of this disease. The authors review the major clinical syndromes and their radiologic manifestations.

Preoperative prediction for the use of cardiopulmonary bypass in lung transplantation.

Cardiopulmonary bypass has been widely used in the management of isolated single and double lung transplantations. Although there are certain clear-cut preoperative indications for cardiopulmonary bypass, in many patients the decision to use this modality is based on the hemodynamic consequences of intraoperative pulmonary artery clamping. We have performed 109 isolated lung transplantations. In 69 patients (38 single lung transplantations and 31 double lung transplantations) cardiopulmonary bypass was initiated only on the basis of intraoperative hemodynamics. We have analyzed preoperative data from these 69 patients to determine whether an intraoperative requirement for cardiopulmonary bypass can be predicted. Of 38 single lung transplantations, 12 necessitated cardiopulmonary bypass (all patients had restrictive lung disease). No patients with obstructive lung disease who underwent single lung transplantation required cardiopulmonary bypass (p < 0.001). For single lung transplantations, 6-minute walk, the arterial desaturation/oxygen requirements on exercise, and the right ventricular ejection fraction were all significantly different between the cardiopulmonary bypass and noncardiopulmonary bypass groups (p < 0.001). Of 31 double lung transplantations, 10 patients required cardiopulmonary bypass (seven had bronchiectasis, two had obstructive lung disease, and one had restrictive lung disease). For obstructive lung disease, no preoperative parameters predicted cardiopulmonary bypass. In conclusion, cardiopulmonary bypass is not necessary for most patients undergoing lung transplantation (in the absence of an absolute preoperative indication). Obstructive lung disease rarely necessitates cardiopulmonary bypass. In single lung transplantations, the subsequent requirement for cardiopulmonary bypass can be predicted from preoperative cardiopulmonary performance. For double lung transplantations, the requirement for cardiopulmonary bypass is usually dependent on unpredictable intraoperative factors.

A comparison of preoperative and postoperative nutritional states of lung transplant recipients.

Malnutrition is a documented problem in some types of endstage lung disease (ESLD). Recently, isolated lung transplants have successfully reversed the respiratory failure of patients suffering from ESLD. In this study, we compare the preoperative and postoperative nutritional states of lung transplant recipients using weight-to-height ratios, anthropometric measurements, subjective global assessment, and biochemical blood values. Patients with emphysema, cystic fibrosis, and other types of bronchiectasis, but not patients with pulmonary fibrosis or pulmonary hypertension, were malnourished preoperatively. All groups had normal biochemical profiles. Caloric intake of patients with cystic fibrosis and bronchiectasis was increased above predicted basal energy expenditure levels. By six months to one year postoperatively, all groups of malnourished patients had significantly improved their nutritional status. Emphysema patients improved nutrition by maintaining preoperative caloric intake levels--however, both cystic fibrosis and bronchiectasis patients were able to achieve the same goal with significantly decreased caloric intakes. We conclude that malnourished ESLD patients receiving isolated lung grafts are able to achieve normal nutrition within one year posttransplant. Since this occurs in all cases with a reduced, or at best maintained, caloric intake, more study is needed to elucidate the factors that contribute to ESLD malnutrition.

Prospective assessment of a standardized pathologic grading system for acute rejection in lung transplantation.

Using the recent standardization of the pathologic definitions for acute lung rejection, we prospectively evaluated 66 consecutive bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) specimens in 32 patients after lung transplantation. Clinical indications for bronchoscopies were surveillance (n = 44), rejection (n = 18), and infection (n = 4). Bronchoalveolar lavages were obtained from the right middle lobe or lingula in single lung transplant and from both sites in double lung transplant recipients. Cytosmears for differential cell counts were performed and 400 to 500 cells were counted. Five to eight TBB specimens were taken from two different lobes and stained with hematoxylin-eosin, elastic trichrome, and silver methenamine. Sixty-four of 66 sets of biopsy specimens were satisfactory, but 3 were eliminated because of presence of cytomegalovirus cytopathic changes. Of the remaining 61, rejection was presented in 45 (74 percent): grade 1 in 23 (38 percent), grade 2 in 19 (31 percent), and grade 3 in 3 (5 percent). In 30 of 42 (71 percent) surveillance biopsy specimens, rejection was present, grade 1 in 18 (43 percent) and grade 2 or 3 in 12 (28 percent). In TBBs performed for clinical suspicion of rejection, 15 of 18 TBB specimens (83 percent) showed rejection, grade 1 in 5 (28 percent) and grade 2 or 3 in 10 (55 percent). Of four biopsies performed for suspicion of infection, one was normal and three showed rejection in addition to infection. These three were eliminated from further analysis due to the limitation of the Lung Rejection Study Group criteria in distinguishing rejection from infection. Of the 45 episodes of rejection, 24 (53 percent) occurred during the first 3 months posttransplantation, 8 (18 percent) between 3 and 6 months and 13 (29 percent) after 6 months. Percentage of BAL lymphocytosis was significantly elevated in grade 2 or 3 rejection (28 +/- 4) when compared with grade 1 (15 +/- 3) or grade 0 (10 +/- 3) (p < 0.001). Bronchoalveolar lavage lymphocytosis also correlated with severity of rejection (r = 0.6). We conclude that according to the standardized criteria of the Lung Rejection Study Group, acute lung rejection occurs more frequently than clinically suspected early and late after transplantation and that BAL lymphocytosis correlates with the presence and severity of histologically proven rejection.

Lung transplantation in patients over the age of 50.

It is common to assign an upper age limit for potential lung transplant recipients. The influence of age on LTX outcome is, however not, documented. A review of our first 103 LTXs, 51 single LTXs and 52 double LTXs, includes 31 recipients aged 50-63 years (mean 55.3 +/- 3.9); 19 received single LTX, and 12 received double LTX. Indications for LTX in those aged greater than 50 included proportionately more patients with emphysema and interstitial lung disease. Actuarial survivals in those aged less than 50 at 12, 36, and 60 months were 68%, 60%, and 55%, and in those aged greater than 50 was 70%, 61%, and 61%, respectively. The causes of death reflect a tendency of younger patients to die from graft rejection and older patients to die from sepsis. Acute rejection more than 6 weeks posttransplant and chronic rejection were less frequent in older patients (P < 0.05). The 6-minute walk and modified Bruce protocol tests, the incidence of CMV pneumonitis, and the late post-LTX renal function were not related to age. In conclusion, in carefully selected candidates in their sixth and seventh decades, LTX is an acceptable operation for end-stage lung disease. The tendency of older patients to a lower incidence of late allograft rejection (acute or chronic) may reflect decreased immunological responsiveness with age.

Pseudomonas cepacia in lung transplant recipients with cystic fibrosis.

Twenty-four isolated double lung transplants (LTXs) have been performed in 22 patients with cystic fibrosis, with a follow-up of 4 to 47 months. Prior to LTX, all patients were colonized with Pseudomonas aeruginosa, and ten patients were also colonized with Pseudomonas cepacia. Both organisms were specifically sought before LTX. All patients who grew P cepacia before LTX did so after LTX. Five additional patients only grew this bacterium after LTX. There was no difference between those who grew P cepacia and those who did not in terms of data before LTX for age, weight, pulmonary function, and 6-min walk. After LTX, 7 of the 15 patients who had ever grown P cepacia died. No patient who grew only P aeruginosa died. The median survival in the subgroup with P cepacia was 28 days. Five of the seven died as a direct result of P cepacia pneumonia and sepsis. One died of cyclosporin A (cyclosporine) neurotoxicity with concurrent P cepacia pneumonia, and one died at the time of a retransplant for graft failure (associated with three bouts of P cepacia pneumonia and cytomegalovirus). Four of seven had not grown this bacterium before LTX. There were no perioperative factors, including antibiotic choices, that distinguished survivors and nonsurvivors. Overall 1-year survival is about 70 percent (15/22). Fourteen bouts of P cepacia pneumonia occurred in 12 patients. Four empyemas, one lung abscess, one suppurative pericarditis, and five cases of sinusitis were also due to this bacterium. In conclusion, P cepacia is responsible for excess morbidity and mortality after LTX. This organism is particularly lethal if isolated for the first time after LTX. Factors predicting its acquisition in this setting are unknown. While it is possible that the facial sinuses may act as an unrecognized reservoir or that patients or equipment provide a source, further study into the epidemiology of this organism is necessary to improve the survival of colonized patients undergoing LTX.

Hypersensitivity pneumonitis and airways hyperreactivity induced by occupational exposure to penicillin.

A patient with penicillin-induced hyperreactive airways in association with hypersensitivity pneumonitis is described. Patch tests and intradermal tests to penicillin were positive. Bronchoalveolar lavage demonstrated a relative lymphocytosis and mild neutrophilia. Symptoms and physiologic abnormalities of pulmonary function and gas exchange resolved on cessation of exposure to penicillin.

Isolated lung transplantation.

A clinical reality since 1981, lung transplantation is now generally accepted as a useful procedure for patients with end-stage lung disease. Early attempts at lung transplantation were marked by infection, rejection, and, in particular, bronchial dehiscence. Obliterative bronchiolitis, an airway-targeted form of chronic rejection, continues to be a problem. It is associated with all types of lung transplantation and is an important cause of late death. In the past few years advances in surgical technique, organ preservation and postoperative management have all contributed to improved survival and preservation of lung function. The shortage of suitable organ donors remains the limiting factor in clinical programs worldwide and curtails more widespread application of lung transplantation.