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Biomedical subjects

R Breuer

Publications and source records attributed to R Breuer.

At least 37 records · Page 2Linked to original sources

[Circulating adhesion molecules (cICAM-1, lcVCAM-1) in patients with suspected inflammatory heart muscle disease].

UNLABELLED: Some patients with non-ischemic heart failure show inflammatory changes in the myocardium which are thought to be of causal or pathogenetic relevance for the heart failure. The intercellular adhesion molecule-1 (ICAM-1) and the vascular adhesion molecule-1 (VCAM-1) are membrane proteins with receptor function from the immunoglobulin superfamily which mediate the vascular adhesion and transmigration of leucocytes into the tissue and undergo increased expression in chronic immunological-inflammatory processes. In addition to membrane-bound adhesion molecules, soluble forms can be detected in serum. In the present study we investigated the occurrence and the significance of circulating ICAM-1 and VCAM-1 in 71 patients with non-ischemic heart failure (47 M/24 F, mean age: 55 +/- 11 years). METHODS: Serum concentrations of cICAM-1 and cVCAM-1 were analyzed using ELISA-Kits. The severity of heart failure was assessed in accordance to the NYHA-classification and to hemodynamic parameters (mean pulmonary pressure, left ventricular ejection fraction). Inflammatory heart disease was assessed histologically and immunohistologically (T-lymphocytes > 7.0/mm2, increased expression of the histocompatibility antigens of class I and II) in right ventricular endomyocardial biopsies. 16 healthy, age-matched patients (8 M/8 F, mean age: 55 +/- 6 years, mean ejection fraction 76 +/- 3%) without signs of inflammation in the myocardium (mean T-lymphocytes < 3.5 cells/mm2, low expression of HLA-class I and II) served as controls. RESULTS: The mean serum concentrations of circulating ICAM-1 and VCAM-1 (cICAM-1, cVCAM-1) were higher in patients with non-ischemic heart failure (372 +/- 107 ng/ml and 949 +/- 439 ng/ml) than controls (264 +/- 37 and 710 +/- 164 ng/ml) (p < 0.05). The mean concentrations of both adhesion molecules varied as a function of the mean pulmonary pressure and the left ventricular ejection fracture (for cICAM-1: Pearson's r: 0.24 and -0.33, p < 0.05; for cVCAM-1: Pearson's r: 0.28 and -0.26, p < 0.05). In 38% (n = 16) of patients with elevated concentrations of cICAM-1 (> or = 337 ng/ml) and 41% (n = 7) of those with elevated serum levels of cVCAM-1 (> or = 1038 ng/ml), the myocardial biopsies showed increased lymphocytic infiltration between 7 and 22 T-lymphocytes/mm2 and an enhanced expression of the MHC antigens of class I/II as sign of an activated inflammatory process in the myocardium. All patients with more than 9.3 T-lymphocytes/mm2 in the myocardium (n = 7) had higher serum levels of cICAM-1 (447 +/- 146 ng/ml, p < 0.05 compared to controls) and of cVCAM-1 (1577 +/- 688 ng/ml, p < 0.001). Both adhesion molecules correlated significantly with the mean number of T-lymphocytes in the myocardium (Pearson's r: 0.31-0.37, p < 0.05). SUMMARY AND CONCLUSION: The present study shows that the elevated levels of cICAM-1 and cVCAM-1 are often found in the serum of patients with non-ischemic heart failure. These raised serum levels correlate with inflammatory infiltrates in the myocardial tissue and with the clinical and hemodynamic signs of heart failure, thus, confirming a connection between heart failure and inflammatory changes in the myocardium.

Adult↗

Peribronchial lymphocyte activation in bleomycin-induced lung injury.

The role of lymphocytes in bleomycin (Bleo)-induced lung injury remains obscure. In normal hamsters, peribronchial lymphatic tissue (PBLT) has been found to contain a large population of T lymphocytes responsive to interleukin 2 (IL-2) but not to IL-4. Lung injury induced by a single intratracheal instillation of Bleo in hamsters has been ameliorated by cyclosporin A (CyA). In the present study, using this model, PBLT-derived lymphocyte function was explored for 28 days after Bleo instillation. Increase in PBLT lymphocytes occurred at five time points investigated, reaching highest values on day +7 (p < 0.0025). Cell proliferation in response to concanavalin A was enhanced, while IL-2 +/- the mitogen had no effect. In contrast to its inactivity in the normal hamster, in the Bleo-injured animal IL-4 alone induced T cell proliferation (p = 0.0077) on day +7. CyA therapy initially suppressed and delayed recovery of the number of lymphocytes and their activation. The results of this study suggest the existence of a vulnerable period in Bleo-induced lung injury and indicate that lymphocytes participate in the pathogenesis of the insult to the tissue. The unresponsiveness to IL-2 and the emergence of cellular response to IL-4 indicate immune deviation in PBLT-derived T cells.

Animals↗

Use of fiberoptic bronchoscopy in bone marrow transplant recipients.

Bone marrow transplantation (BMT) has become the therapy of choice for a number of malignant and nonmalignant hematologic and nonhematologic disorders. A frequent complication after BMT is pulmonary disease which is associated with a high mortality rate. We examined the results of 79 bronchoscopies performed between May 1991 and May 1995 in 62 patients for the evaluation of pulmonary complications after BMT. In all cases bronchoalveolar lavage (BAL) was performed, in 10% transbronchial biopsy (TBB) was also carried out and in 13% bronchoscopy was followed by open lung biopsy. Positive results were found in 67% of bronchoscopies. Fungal infection (Candida and Aspergillus species) was the most common finding (18%), bacterial infection was found in 13%, mixed (fungal and bacterial) infection in 6%, cytomegalovirus in 11% and Pneumocystis carinii pneumonia in 4%. Diffuse alveolar hemorrhage was detected in 11% of cases. Idiopathic pneumonia syndrome (IPS) was diagnosed by TBB in 3% of procedures. We conclude that BAL is a safe and accurate procedure for the evaluation of pulmonary complications after BMT. TBB should be considered in the absence of thrombocytopenia for the diagnosis of IPS. If bronchoscopy findings are negative, open lung biopsy should be considered.

Adolescent↗

Colchicine does not ameliorate bleomycin-induced pulmonary injury in hamsters.

We have evaluated the effect of colchicine, a potential antifibrotic drug, on bleomycin-induced pulmonary inflammation in hamsters. Pulmonary injury was induced by a single intratracheal (IT) instillation of bleomycin (bleo). Four groups of male Syrian hamsters each received one of four treatments: (1) IT bleo and twice daily intraperitoneal (IP) injections of colchicine (col) starting one day before IT instillation of bleo (bleo-col); (2) IT bleo and IP injections of saline (bleo-sal); (3) IT saline and IP colchicine (sal-col); and (4) IT saline and IP saline (sal-sal). Animals were sacrificed 28 days after IT treatment. Lung injury was evaluated histologically, biochemically and by analysis of bronchoalveolar lavage (BAL) fluid. Treatment of hamsters with colchicine did not ameliorate the bleo-induced lung injury, as determined by a semiquantitative morphological index that assesses the severity and extent of the lung injury on a scale of 0-3. Lung hydroxyproline measurements and BAL fluid cell count were also similar in bleo-col compared to bleo-sal hamsters. Colchicine did not prevent the bleo-induced restriction expressed by volume displacement. These results indicate that colchicine does not ameliorate the bleo-induced lung inflammation and fibrosis and call for further controlled investigations to justify the use of this drug in pulmonary disorders.

Animals↗

Bleomycin-induced lung injury is enhanced by interferon-alpha.

We have evaluated the effect of intraperitoneal (I.P.) injection of human recombinant interferon-2alpha (IFN-alpha) on Bleomycin-induced pulmonary injury in hamsters. Pulmonary injury was induced by a single intratracheal (I.T.) instillation of Bleomycin (Bleo). Six groups of male Syrian hamsters were treated as follows: 1) I.T. Bleo and daily I.P. injections of low-dose interferon-alpha (2 x 10(4) U), 2) I.T. Bleo and daily I.P. injections of high-dose interferon-alpha (10(5) U), 3) I.T. Bleo and I.P. injections of saline, 4) I.T. saline and I.P. low-dose IFN-alpha, 5) I.T. saline and I.P. high-dose IFN-alpha, 6) I.T. saline and I.P. saline. Animals were sacrificed 28 days after I.T. treatment. Lung injury was evaluated histologically and biochemically. Treatment of hamsters with low-dose but not high-dose IFN-alpha significantly augmented the Bleo-induced lung injury, as determined by a semiquantitative morphological index. Lung hydroxyproline measurements were highest in Bleo-low-dose-IFN-alpha followed by Bleo-high-dose-IFN-alpha and Bleo-Sal as compared to Sal-Sal and Sal-IFN-alpha controls. These results suggest that IFN-alpha augments Bleo-induced lung injury but that this effect is complex and does not follow a simple-dose-response pattern.

Animals↗

Differential diagnosis of pleural effusion by lactate dehydrogenase isoenzyme analysis.

STUDY OBJECTIVE: To determine the diagnostic value of pleural fluid lactate dehydrogenase (LDH) isoenzyme analysis in the differential diagnosis of pleural fluid. PATIENTS AND METHODS: Eighty-seven consecutive patients with pleural effusion caused by congestive heart failure (33), infection (33), and malignancy (21) comprised a derivation set of patients. Pleural fluid LDH activity and isoenzyme pattern were established in all patients and analyzed by the classification and regression trees (CART) method. An additional group of 20 consecutive patients comprised a validation set that was used for cross-validation of CART-derived decision tree. RESULTS: A decision tree, with a positive predictive value of 83%, was constructed and validated by data from a validation set of patients. CONCLUSIONS: Pleural fluid LDH isoenzyme pattern may be helpful for the differential diagnosis of the most common causes of pleural effusions: congestive heart failure, infections, and malignancy.

Algorithms↗

CT-guided biopsy of peripheral lung lesions associated with BOOP.

Diagnosis of Bronchitis Obliterans with Organizing Pneumonia (BOOP), has been carried out thus far by open lung biopsy, or by transbronchial biopsy. We report a patient who presented with fever, cough and dyspnea. A transthoracic CT-guided biopsy of a peripheral lesion resulted in the diagnosis of BOOP. The histological findings were also confirmed by a transbronchial biopsy. It is suggested that transthoracic CT-guided biopsy should be considered for the evaluation of peripheral lung lesion compatible with BOOP.

Adult↗

Clustering of Pneumocystis carinii pneumonia in patients undergoing renal transplantation from living unrelated donors in Iraq and India.

Over the past few years, we have observed a substantial increase in the number of patients followed at our hospital who have undergone renal transplantation from living unrelated donors (LURD). These transplants were all performed in one of two centers: Bagdad, Iraq or Bombay, India. We have observed a parallel increase in the number of cases of Pneumocystis carinii pneumonia (PCP) post-renal transplant. We conducted a ten-year retrospective analysis (1986-1995) of patients who developed PCP post-renal transplant to determine the risk factors associated with the development of this infection, with particular reference to the type of transplant and the center in which the transplant was performed. Over this period, 270 renal transplant patients were followed at this hospital and 10 episodes of PCP were documented (3.7%). Six of these cases occurred within the last 2 years, as compared to only 4 cases in the preceding 8 years. All of the cases observed in the last 2 years occurred in patients who had undergone renal transplantation from LURD in Iraq or in India. During the same period, we observed no cases of PCP in patients who had undergone transplantation in Israel (cadaver or related living donor transplants). We could find no difference between patients undergoing transplant from LURD and those undergoing other transplants in terms of immuno-suppressive therapy, frequency of organ rejection episodes or coexistent CMV infection. All patients were of Arab descent and live in the West Bank. Although we cannot identify any obvious explanation for this association, we believe that these cases represent a true cluster phenomenon. We therefore feel it is warranted for all recipients of renal transplants from living unrelated donors seen in our hospital to receive prophylactic therapy for Pneumocystis carinii pneumonia.

Adult↗

Bronchiolitis obliterans presenting as subcutaneous emphysema and pneumomediastinum: a case report.

We describe a woman post allogeneic bone marrow transplantation (BMT), who presented to the emergency room with subcutaneous emphysema and pneumomediastinum as the first manifestation of bronchiolitis obliterans complicating mild chronic graft versus host disease (GVHD). In contrast to other patients with pneumomediastinum described in the literature, this patient suffered from only mild GVHD. She did not receive methotrexate as GVHD prophylaxis, and the pneumomediastinum was a presenting manifestation rather than a terminal event. In addition, this is the first description of subcutaneous emphysema with this setting. Therefore, bronchiolitis obliterans should be highly suspected in post-BMT patients presenting with pneumomediastinum and subcutaneous emphysema, and prompt therapy should be initiated.

Acute Disease↗

Pulmonary involvement in lymphoma.

Intrathoracic involvement is common in both Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). The most common manifestation is mediastinal lymphadenopathy. In HD, nodal involvement is by contiguity and usually involves the superior mediastinum, while the findings in NHL are more variable. Pulmonary parenchymal disease occurs in 38% of HD and 24% of NHL. In untreated HD, parenchymal involvement is invariably associated with mediastinal lymphadenopathy and often with widespread disease. Three distinct radiological patterns of pulmonary lymphoma are recognised: nodular, bronchovascular-lymphangitic and pneumonic-alveolar. Rarely lymphoma may be endobronchial. Pleural effusion occurs in 16% of lymphoma patients and is usually associated with disease elsewhere. It is frequently caused by lymphatic obstruction but may be due to direct pleural involvement by tumour. Chylothorax may occur in NHL but is unusual in HD. Diagnosis of intrathoracic lymphoma is by transbronchial or transthoracic biopsy or by needle aspiration of tissue or pleural fluid. The addition of immunostaining improves the diagnostic yield in equivocal cases. Treatment and prognosis vary depending on cell-type, location and extent of disease.

Acquired Immunodeficiency Syndrome↗

Bacterial pneumonia in recipients of bone marrow transplantation. A five-year prospective study.

Bacterial pneumonia as an important complication of bone marrow transplantation (BMT) has not been subjected to comprehensive analysis. Two hundred fifty-five consecutive allogeneic and autologous BMT recipients, ranging in age from 1 month to 53 years, were prospectively followed for 3 days to 3 years (median, 108 days) for development of bacterial pneumonia. Etiology, place acquired, chest radiography, and outcome were recorded and the association between bacterial pneumonia and demographic and clinical variables was analyzed. Thirty-seven (15%) patients experienced 52 episodes of bacterial pneumonia: onset of 13 episodes occurred within 30 days after transplantation, 10 episodes occurred on days +31 to +100, and 29 episodes occurred thereafter. Bacterial pneumonia was the terminal event or contributed to fatal outcome in 8 patients (22% of bacterial pneumonia cases, 3% total study population). Mortality due to hospital-acquired pneumonia (6/21) was significantly higher than (P = 0.03). Bacterial pathogens were identified in 27 (52%) episodes. During the first 100 days after BMT, hospital-acquired Gram-negative bacteria predominated, caused mainly by Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter lwoffi, and Enterobacter cloacae. After day +100, community-acquired, Gram-positive bacteria predominated, particularly Streptococcus pneumoniae. Haemophilus influenzae occurred periodically. Considering all episodes, significant association was found between bacterial pneumonia and veno-occlusive disease (VOD) (P < 0.01) and chronic graft-versus-host disease (GVHD) (P < 0.02). For culture-positive episodes, the association between bacterial pneumonia and VOD was significant (P < 0.001) and borderline for acute GVHD (P = 0.07). It is concluded that VOD and GVHD are positively associated with post-BMT bacterial pneumonia. Its incidence, etiology, risk factors, and outcome are important considerations in its prevention and treatment.

Adolescent↗

Control of inflammatory processes by cell-impermeable inhibitors of phospholipase A2.

Cell-impermeable inhibitors of phospholipase A2 were prepared by linking inhibiting molecules to macromolecular carriers which prevent the inhibitor's internalization. These preparations inhibit the release of oxygen reactive species from neutrophils and cell death induced by inflammatory agents, as well as bleomycin-induced lung injury.

Animals↗

Abatement of bleomycin-induced pulmonary injury by cell-impermeable inhibitor of phospholipase A2.

The mechanism of bleomycin (Bleo)-induced pulmonary injury is not fully understood. Elevated levels of lung phospholipase A2 (PLA2) have been previously reported following intratracheal (IT) instillation of Bleo, but the role of this enzyme in the pathogenesis of lung injury is not clear. In this pilot study, we have evaluated the effect of a cell impermeable inhibitor of PLA2 (CME) on Bleo-induced pulmonary inflammation in hamsters. Pulmonary injury was induced by a single IT instillation of Bleo (1 unit/0.5 ml saline). Three groups of male Syrian hamsters were evaluated: 1) BLEO-CME animals received IT Bleo and daily intraperitoneal (IP) injections of CME (1 mumole/kg), starting 1 day before IT instillation; 2) BLEO-SAL animals--received IT Bleo and IP injections of saline and 3) SAL-SAL animals--treated with IT and IP administrations of saline. Animals were sacrificed 14 days after IT treatment and lung injury was evaluated histologically by a semiquantitative morphologic index and by a differential cell count of bronchoalveolar lavage fluid. CME treatment significantly ameliorated Bleo-induced lung injury compared to BLEO-SAL animals (P < 0.05). The percentage of neutrophiles in bronchoalveolar lavage fluid was reduced from 17.7 +/- 3.2% (mean +/- S.E.) in BLEO-SAL group to 7.3 +/- 1.7% in BLEO-CME group (P < 0.05), achieving levels comparable to SAL-SAL control animals. These results suggest that treatment with an extracellular PLA2 inhibitor-CME abates Bleo-induced pulmonary injury. This may indicate an active role of PLA2 in the pathogenesis of interstitial pulmonary fibrosis.

Animals↗

Elastin and collagen degradation products in urine of smokers with and without chronic obstructive pulmonary disease.

It has been hypothesized that emphysema results from damage to the elastic fiber network of the lungs as a result of elastase-antielastase imbalance. We used a new assay for urinary desmosine (DES) and isodesmosine (IDES), specific markers for the degradation of mature crosslinked elastin, and hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), specific markers for the degradation of mature crosslinked collagen, in order to examine elastin and collagen degradation in relation to current cigarette smoking and the presence of chronic obstructive pulmonary disease (COPD). The study sample consisted of 22 never-smokers (NSM group), 13 current smokers without airflow obstruction (SM group), and 21 patients with COPD (COPD group), including both current and former smokers. The relation between the creatinine-height index and FEV1 was used to correct for possible loss of muscle mass and decreased excretion of creatinine in the COPD group. Mean urinary excretion of elastin-derived crosslinks in the COPD group (DES, 11.8 +/- 5.1 [mean +/- SD]; IDES, 11.3 +/- 5.0 micrograms/g creatinine) and in the SM group (DES, 11.0 +/- 4.2; IDES, 10.2 +/- 2.5 micrograms/g creatinine) was significantly higher than in the NSM group (DES, 7.5 +/- 1.4; IDES, 6.9 +/- 1.3 micrograms/g creatinine). In multivariate analysis, current smoking and the presence of COPD were significantly and independently associated with higher urinary excretion of elastin degradation products, and there was no significant interaction between current smoking and the presence of COPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cytomegalovirus pneumonia prior to engraftment following T-cell depleted bone marrow transplantation.

CMV pneumonia is a frequent complication of allogeneic bone marrow transplantation (BMT). It usually appears 23 months following transplantation and is associated with a high mortality rate. The incidence of CMV pneumonia in our T-lymphocyte depleted allogeneic BMT recipients, transplanted between 1987-1991, was 18 out of 197 (9.2%) patients. In 3 patients (1.5% of allogenic BMT recipients), pneumonia occurred prior to marrow engraftment, on days 12-16 post BMT. These patients did not develop acute GVHD in contrast to 9/11 patients who had acute GVHD in addition to developing CMV pneumonia between engraftment and day +100 (p < 0.03). Furthermore, these three patients did not receive steroid therapy as opposed to 14/15 patients who were treated with steroids and eventually contracted CMV pneumonia post-engraftment (p < 0.01). The three patients did not have two additional risk factors known for the development of CMV pneumonia: increasing age and a diagnosis of acute myeloblastic leukemia (AML) as the primary disease. Despite prompt diagnosis and therapy with ganciclovir and high doses of intravenous immunoglobulin (IVIG), two of the patients died. Tcell depleted BMT may be a risk factor for development of CMV pneumonia occurring prior to engraftment. In the era of post-BMT anti CMV prophylaxis, one should be aware that life-threatening CMV pneumonia may appear prior to engraftment and consider aggressive CMV prophylaxis.

Adolescent↗