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Biomedical subjects

R Tuder

Publications and source records attributed to R Tuder.

17 recordsLinked to original sources
PubMed2000

COPD: exacerbation.

A renewed interest in the clinical and pathogenic aspects of COPD exacerbation is timely in view of national and global COPD initiatives. The three big problems regarding COPD continue to be the following: prevention of the disease; slowing progression of the disease once diagnosis has been established; and prevention and more effective treatment of the so-called exacerbation. The following assessment will raise more questions than answers and will review some of the past and current concepts and contexts.

Asthma↗
PubMed2000

Lymphomatoid granulomatosis: radiologic features and pathologic correlations.

OBJECTIVE: The purpose of this paper is to define the radiologic features of lymphomatoid granulomatosis and correlate them with histopathologic features. CONCLUSION: Lymphomatoid granulomatosis shows characteristic CT features such as peribronchovascular distribution of nodules, coarse irregular opacities, small thin-walled cysts, and conglomerating small nodules. Large masses and occlusion of large vessels also occur. Histopathologic examination shows the nodules are caused by intravascular and perivascular infiltration by atypical lymphoid cells.

Adult↗
PubMed1999

Mycoplasma pneumoniae-associated bronchiolitis causing severe restrictive lung disease in adults: report of three cases and literature review.

STUDY OBJECTIVES: To characterize adult Mycoplasma pneumoniae-induced bronchiolitis requiring hospitalization. DESIGN: We encountered an adult patient with severe bronchiolitis in the absence of pneumonia due to M. pneumoniae. To determine the relative frequency of such a condition, we retrospectively reviewed the medical records of adults over a 4-year period with a hospital discharge diagnosis of "bronchiolitis" from a university hospital. SETTING: University Hospital of the University of Colorado Health Sciences Center, Denver, CO. STUDY SUBJECTS: From 1994 to 1998, 10 adult inpatients were identified with a diagnosis of bronchiolitis. There were two with respiratory bronchiolitis, one with panbronchiolitis, one patient with bronchiolitis obliterans organizing pneumonia (BOOP), and six with acute inflammatory bronchiolitis. Including the initial patient, three had a definitive clinical diagnosis of Mycoplasma-associated bronchiolitis. RESULTS: The three adult patients with bronchiolitis due to M. pneumoniae are unusual because they occurred in the absence of radiographic features of a lobar or patchy alveolar pneumonia. Hospital admission was occasioned by the severity of symptoms and gas exchange abnormalities. One patient had bronchiolitis as well as organizing pneumonia (BOOP) that responded favorably to corticosteroid treatment. The other two had high-resolution CT findings diagnostic of an acute inflammatory bronchiolitis. One of the patients with inflammatory bronchiolitis had an unusual pattern of marked ventilation and perfusion defects localized predominantly to the left lung. All three had restrictive ventilatory impairment on physiologic testing. CONCLUSIONS: In adults, Mycoplasma-associated bronchiolitis without pneumonia is rarely reported, but in hospitalized patients, it may be more common than expected and may be associated with severe physiologic disturbances.

Adult↗
PubMed1998

Pulmonary capillaritis: a possible histologic form of acute pulmonary allograft rejection.

Acute rejection after lung transplantation occurs commonly and is usually characterized histologically by a perivascular mononuclear infiltrate. We report five cases of pulmonary capillaritis with a histologic appearance distinct from typical rejection, occurring in patients ranging in age from 18 to 45 years, with a variety of underlying diseases including alpha1 antitrypsin deficiency, pulmonary hypertension, cystic fibrosis, and rheumatoid arthritis. Four of the five patients had alveolar hemorrhage histologically, and two had frank hemoptysis. Time of onset ranged from 3 weeks to many months after transplantation. Three cases were fulminant, and there were two deaths. In only one case, with methicillin-resistant Staphylococcus aureus bronchitis, could infection be established. All were treated with intensification of immunosuppressive therapy. Plasmapheresis was carried out in two cases and coincided with temporary improvement, but its efficacy was questionable because of concurrent immunosuppressive therapy. Two had recurrent biopsy-proven acute rejection within 6 weeks of treatment, and one had recurrent severe pulmonary hemorrhage that abated with total lymphoid irradiation. Our experience suggests that pulmonary capillaritis in lung transplant recipients can be an acute, fatal illness with the potential for recurrence in the survivors. We speculate that it represents a form of acute vascular rejection. Early pathologic diagnosis and aggressive immunosuppressive therapy are recommended. Although a humoral component was not documented, the possible response to plasmapheresis requires continued evaluation.

Acute Disease↗
PubMed1997

Diffuse alveolar hemorrhage and systemic lupus erythematosus. Clinical presentation, histology, survival, and outcome.

Diffuse alveolar hemorrhage (DAH) complicating systemic lupus erythematosus (SLE) remains a devastating pulmonary complication of this systemic disease. We conducted this study to review the clinicopathologic presentation and the effects of prior treatment, presence of infection, and current treatment on the survival and outcome of patients with DAH and SLE. We reviewed the records of 15 SLE patients who experienced 19 episodes of DAH over a 10-year period in a single tertiary care hospital. These patients were compared with 57 previously reported cases. The 19 episodes of DAH represented 3.7% of the 510 admissions occasioned by various complications of SLE. As previously reported, the majority (66%) were women with a median age of 27 years. The onset was often abrupt: < 3 days in 12 of the episodes. In 3 patients (20%), DAH was the initial manifestation of SLE, compared with 11% in the literature series. In the other patients in the present series, DAH appeared a median of 31 months following the diagnosis of SLE, versus 35 months in the literature series. In only 42% of the episodes in the present series, compared with 66% in the literature series, was hemoptysis present at the time of admission. However, hemoptysis eventually appeared in all 19 episodes. Temperature elevation (> 38 degrees C) was another inconsistent finding, found in only 5 episodes (26%) in the present series. The most constant concurrent systemic finding was lupus nephritis (14/15 patients). This represents a significant increase when compared with the literature series (29/48 patients). In 8 of 10 patients in whom lung tissue was available, pulmonary capillaritis accompanied the DAH. This represents a marked difference in the underlying histologic pattern when compared with the literature series. In those patients, 72% (31/43 patients) had bland pulmonary hemorrhage, and capillaritis was described in only 6 patients. The overall patient mortality rate was 53% in the current series and 50% in the literature series. Factors associated with an increased mortality in the present series include the following: mechanical ventilation (62%) versus no mechanical ventilation (0%); infection (78%) versus no infection (20%); and cyclophosphamide therapy for the acute DAH episode (70%) versus no cyclophosphamide therapy (20%). The incidence of infection in DAH and SLE (9/19 episodes) is far greater than previously reported (7/ 57 episodes). One possible explanation for this difference is the increased use of outpatient immunosuppressive therapy with monthly intravenous cyclophosphamide therapy for lupus nephritis. Eighteen DAH episodes in the present series were treated with intravenous methylprednisolone. When one combines both the current and literature series experience (16 episodes), the use of plasmapheresis does not improve survival. Of the 7 patients in the present series who survived all episodes of DAH, 6 remain alive a median of 50 months post episode and without recurrence of DAH. Diffuse alveolar hemorrhage is an uncommon but lethal complication of SLE. The survival rate remains unchanged from previous reports. The absence of hemoptysis should not exclude this diagnosis, particularly in those patients who experience an acute pulmonary syndrome with new radiographic infiltrates accompanied by falling hematocrit and the presence of a hemorrhagic bronchoalveolar lavage. Evidence for lupus nephritis is present in the great majority of cases. Most cases demonstrate the histologic pattern of pulmonary capillaritis. The mortality is adversely affected by the need for mechanical ventilation, either the presence of infection at the time of admission or the development of infection in the hospital, and the use of cyclophosphamide for treatment of the acute event.

Adult↗
PubMed1997

Diffuse alveolar hemorrhage with underlying isolated, pauciimmune pulmonary capillaritis.

Diffuse alveolar hemorrhage (DAH) resulting from pulmonary capillaritis typically accompanies the systemic vasculitides and collagen vascular diseases. Isolated pulmonary capillaritis and DAH without systemic disease occurs in patients with antineutrophil cytoplasmic antibodies. However, isolated pulmonary capillaritis and DAH is not described for patients without clinical or serologic evidence for an underlying systemic disease. To describe such patients, we undertook a retrospective chart review of 29 patients with DAH and biopsy-proven pulmonary capillaritis from seven Denver hospitals. Eight (28%) were diagnosed with isolated pulmonary capillaritis without clinical, serologic, or histologic evidence of an associated illness. Their median age was 30 yr. No association with occupational or drug exposures was identified. All had lower respiratory tract symptoms; seven had upper respiratory tract symptoms. None demonstrated systemic disease or evidence of glomerulonephritis. All were antineutrophil cytoplasmic antibody negative. Other serologies were not significant where measured. Direct immunofluorescence studies of lung tissue were negative in five. Six presented with acute respiratory failure, four requiring mechanical ventilation. One died during initial hospitalization; seven survived. Median follow-up is 43 mo (7 to 73 mo). Five remain in remission. Two experienced multiple recurrences of DAH but without development of systemic disease while on therapy. Herein we characterize DAH and isolated pulmonary capillaritis in the absence of clinical, serologic, or histologic evidence indicating an accompanying systemic illness. The prognosis for this group appears favorable.

Adult↗
PubMed1996

Hyperoxia activates NF-kappaB and increases TNF-alpha and IFN-gamma gene expression in mouse pulmonary lymphocytes.

Hyperoxia-associated production of reactive oxygen species leads to neutrophil infiltration into the lungs and increased pulmonary proinflammatory cytokine expression. However, the initial events induced by hyperoxia, and leading to acute inflammatory lung injury, remain incompletely characterized. To explore this issue, we examined nuclear transcriptional regulatory factor (NF-kappaB and NF-IL-6) activation and cytokine expression in the lungs following 12 to 48 h of hyperoxia exposure. No increases in cytokine (IL-1beta, IL-6, IL-10, TGF-beta, TNF-alpha, IFN-gamma) expression nor in NF-kappaB activation were found after 12 h of hyperoxia. Following 24 h of hyperoxia, NF-kappaB activation and increased levels of TNF-alpha mRNA were present in pulmonary lymphocytes. By 48 h of hyperoxia, amounts of IFN-gamma and TNF-alpha protein as well as mRNA were increased in the lungs, and NF-kappaB continued to show activation, even though no histologic abnormalities were present. These results show that hyperoxia activates NF-kappaB in the lungs before any increase in proinflammatory cytokine protein occurs, and suggest that NF-kappaB activation may represent an initial event in the proinflammatory sequence induced by hyperoxia.

Animals↗
PubMed1996

Lung transplantation: indications, donor and recipient selection, and imaging of complications.

Lung transplantation has become a well-established treatment for end-stage pulmonary parenchymal and vascular disease. Careful selection of recipients and donors is important to decrease early graft failure, which is primarily due to rejection and bronchial dehiscence. Common complications include the reimplantation response, acute rejection, pleural effusion, lymphoproliferative disorders, bronchiolitis obliterans, infection, and airway stenosis or dehiscence. The reimplantation response is a form of noncardiogenic pulmonary edema that begins soon after surgery and resolves in days to weeks. Acute rejection occurs in most recipients; a dramatic response to steroid therapy is the most diagnostic clinical feature. Lymphoproliferative disorders are posttransplantation neoplasms that may disappear when immunosuppressive therapy is stopped and often manifest as a discrete lung mass. In bronchiolitis obliterans-a major long-term complication probably due to chronic rejection-computed tomography (CT) often shows bronchial dilatation and air trapping. Airway stenosis and dehiscence are easily diagnosed with bronchoscopy and CT. Infections remain the major cause of morbidity and mortality.

Adult↗
PubMed1996

Polyarteritis nodosa with pulmonary vasculitis.

Although early postmortem series reported pulmonary involvement as a relatively common manifestation of polyarteritis nodosa (PAN), using the modern classification of PAN pulmonary involvement is very uncommon. A 62-yr-old male with well-documented classic PAN was found to have an arteritis of medium-sized muscular pulmonary arteries. The patient subsequently demonstrated a complete response to treatment. Of the few reported cases of PAN with pulmonary manifestations, the majority are autopsy series and the vascular lesion involves the bronchial arteries. There are no case reports of patients with pulmonary involvement of PAN who responded successfully to treatment. This case is the first description of a premortum diagnosis of pulmonary arteritis in PAN in which the patient had a response to treatment.

Alkylating Agents↗
PubMed1995

Phosphatidic acid signaling mediates lung cytokine expression and lung inflammatory injury after hemorrhage in mice.

Because phosphatidic acid (PA) pathway signaling may mediate many basic reactions involving cytokine-dependent responses, we investigated the effects of CT1501R, a functional inhibitor of the enzyme lysophosphatidic acid acyltransferase (LPAAT) which converts lysophosphatidic acid (Lyso-PA) to PA. We found that CT1501R treatment not only prevented hypoxia-induced PA increases and lyso-PA consumption in human neutrophils, but also prevented neutrophil chemotaxis and adherence in vitro, and lung injury and lung neutrophil accumulation in mice subjected to hemorrhage and resuscitation. In addition, CT1501R treatment prevented increases in mRNA levels and protein production of a variety of proinflammatory cytokines in multiple lung cell populations after blood loss and resuscitation. Our results indicate the fundamental role of PA metabolism in the development of acute inflammatory lung injury after blood loss.

Acyltransferases↗
PubMed1995

Contribution of tumor necrosis factor-alpha to pulmonary cytokine expression and lung injury after hemorrhage and resuscitation.

OBJECTIVE: To examine the role of tumor necrosis factor-alpha (TNF-alpha) in producing acute inflammatory lung injury after hemorrhage and resuscitation. DESIGN: Prospective, controlled animal study. SETTING: Research laboratory. SUBJECTS: Male BALB/c mice. INTERVENTIONS: Treatment with rat antimouse monoclonal anti-TNF-alpha antibodies or control rat immunoglobulin G 1 hr after 30% blood volume hemorrhage and resuscitation. MEASUREMENTS AND MAIN RESULTS: Therapy with monoclonal anti-TNF-alpha antibodies prevented the posthemorrhage increases in pulmonary TNF-alpha and interferon-gamma protein levels that normally occur after blood loss. Administration of monoclonal anti-TNF-alpha antibodies also diminished the increases in interleukin-1 beta, interleukin-6, and interleukin-10 mRNA, but not the increases in TNF-alpha and interferon-gamma mRNA, which are found in the lungs following hemorrhage. In addition, therapy with monoclonal anti-TNF-alpha antibodies was associated with significant improvement in the histologic parameters of posthemorrhage lung injury, particularly intra-alveolar hemorrhage and pulmonary vascular congestion. CONCLUSIONS: These results indicate that TNF-alpha has an important role in the development of acute inflammatory lung injury after blood loss. Blockade of TNF-alpha with monoclonal antibodies significantly reduces hemorrhage-induced lung injury.

Animals↗
PubMed1995

Quantifying oxidative injury in the liver.

Oxidative injury is a mechanism common to both ischemia-reperfusion (IR) and leukocyte-mediated injury. Reperfused tissue beds and elaborated mediators can activate a cascade of intercellular and interorgan injuries that often precipitates multiple organ failure. Initiation of lung injury by gut IR is a case in point, but concomitant liver injury may have been overlooked because of the absence of comparably sensitive physiological markers. In this study, we explore the hypothesis that occurrence of portally derived oxidant-induced liver dysfunction may be detected with both sensitivity and specificity. We simulated pure oxidative injury to the liver and separated the contributions from secondary systemic oxidation. Both tissue and plasma indicators were evaluated, each reflecting aspects of oxidation, membrane integrity, and metabolic function. Tissue markers readily detect oxidative liver injury, but systemic 3-hydroxybutyrate (3-OHB) concentration and ketone body ratio (KBR) are the most sensitive. Comparison of 3-OHB concentrations against the corresponding KBR can be used to distinguish adjustments within a physiological range from the transition into injury.

3-Hydroxybutyric Acid↗
PubMed1995

Hemorrhage and resuscitation alter the expression of ICAM-1 and P-selectin in mice.

Acute inflammatory lung injury is a common clinical occurrence following blood loss and trauma, and is characterized by massive neutrophil infiltration into the lung. In order to better examine cell trafficking that may contribute to lung injury in this setting, we investigated in vivo mRNA levels and immunohistochemically determined expression of the adhesion molecules P-selectin and the intercellular adhesion molecule (ICAM)-1 in murine lungs over the 3-day period following hemorrhage and resuscitation. Significant increases in P-selectin mRNA levels were present in lungs obtained 3 days after hemorrhage. ICAM-1 mRNA levels were significantly increased 6 and 72 hr after hemorrhage. Immunohistochemical staining for P-selectin was enhanced on pulmonary vascular endothelium in all visible vessels at 6, 24, and 72 hr after hemorrhage. ICAM-1 immunoreactivity was significantly increased on the alveolar epithelium at 6 and 72 hr post-hemorrhage. These results suggest that increased expression of adhesion molecules in the lung at early post-hemorrhage timepoints may contribute to neutrophil infiltration into the lungs and the frequent development of acute lung injury following blood loss and trauma.

Animals↗
PubMed1994

Regulation of alveolar type II cell differentiation and proliferation in adult rat lung explants.

Alveolar type II cells produce pulmonary surfactant and serve as the stem cell of the alveolar epithelium by proliferating and transforming into type I cells. The study of the differentiated function and proliferative capacity of type II cells in response to injury in vivo has been hindered by the complexity of the systemic response to injury. In vitro studies have in turn been limited by the impaired proliferative potential and loss of markers of differentiation in isolated type II cells maintained in culture. We describe an in vitro system in which type II cells proliferate spontaneously and simultaneously maintain differentiated characteristics. Other investigators have maintained slices of adult lung in culture after agarose infusion for up to 9 wk. To further develop this model for the study of epithelial cell differentiation and proliferation, we assessed epithelial differentiation, proliferative capacity, and regulation of cell-specific gene expression in slice explants of agarose-infused rat lungs. We prepared 1-mm-thick explants and maintained them in culture for up to 2 wk. Maintenance of differentiation was confirmed morphologically by light and electron microscopy, by the accumulation of epithelial cell-specific surfactant proteins, and by phospholipid analysis. Proliferative capacity was assessed by measuring [3H]thymidine incorporation in alveolar and small airway cells at baseline and in response to growth stimuli. Type II cell proliferation was inhibited in a dose-dependent manner by glucocorticoids. Glucocorticoids regulated RNA levels in explants in a manner similar to that seen in vivo and in fetal lung explants. The alveolar epithelium in adult lung slice explants maintains differentiated function and the ability to proliferate, thereby providing a useful system for the study of distal airway and alveolar cell homeostasis and response to injury.

Animals↗
PubMed1994

Bronchiolitis obliterans: the lone manifestation of rheumatoid arthritis?

The patient was a 62 year old man, who suddenly developed obstructive lung disease without a readily definable cause. He had a remarkable family history of deforming rheumatoid arthritis, and a serum rheumatoid factor of 1:1,256, but with no evidence of active rheumatological disease. Clinical, physiological and radiologic features suggested bronchiolitis obliterans, and this was confirmed by open lung biopsy. Immune staining of tissue revealed immunoglobulin M (IgM) as well as rare immunoglobulin (IgG) containing plasma cells in a peribronchiolar location. Because of these findings, we suggest that this case represents bronchiolitis obliterans secondary to a rheumatoid process. This case is unusual since it appeared in a man and is the first and, so far, the only manifestation of rheumatoid arthritis. Prior studies indicate that the bronchiolitis obliterans of rheumatoid arthritis occurs primarily in women and only in ongoing cases.

Arthritis, Rheumatoid↗