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Biomedical subjects

J E Gadek

Publications and source records attributed to J E Gadek.

At least 19 recordsLinked to original sources
PubMed1997

Serum vitamin E decreases in HIV-seropositive subjects over time.

Vitamin E is an important lipid soluble antioxidant that has a number of crucial functions including protecting lipids from oxidative damage. It also may play an important role in enhancing the immune response in subjects with Human Immunodeficiency Virus (HIV) infection. The current study measured the serum level of vitamin E in 121 HIV seropositive subjects with no prior pulmonary complications. Although the mean level was normal at 9.0 +/- 0.5 microg/ml, 22.3% of the subjects had a deficient level of less than 5 microg/ml. In addition, 42 subjects were studied longitudinally and serum vitamin E levels were determined at baseline and 12 months later. The mean serum vitamin E level in this group significantly decreased after 12 months compared with baseline levels (5.9 +/- 0.5 microg/ml compared with 9.6 +/- 0.9 microg/ml, p = 0.001). The CD4 counts also were significantly decreased after 12 months (460.6 +/- 36.0 cells/mm3 versus 390.5 +/- 37.7 cells/mm3, p = 0.032). No significant correlations were observed between the decrease in serum vitamin E and the change in CD4 count, body mass index (BMI), or serum albumin levels over the 12-month period. In conclusion, a significant portion of HIV-seropositive subjects have a deficiency in serum vitamin E early in the course of their disease. Furthermore, there is a significant decrease in serum vitamin E levels in these subjects over 12 months.

Adult↗
PubMed1997

Alveolar fluid glutathione is not reduced in asymptomatic HIV-seropositive subjects.

Glutathione is an important antioxidant tripeptide that is found in high concentrations in the epithelial lining fluid (ELF) of the lung. Previous investigators demonstrated a deficiency of glutathione (GSH) in the epithelial lining fluid of human immunodeficiency virus (HIV)-seropositive patients. The current investigation performed bronchoalveolar lavage (BAL) on 59 asymptomatic HIV-seropositive subjects (mean CD4: 365.9 +/- 31.2 cells/mm3) and 12 normal control subjects. The volume of ELF and the concentration of glutathione and oxidized glutathione were determined. The concentration of total GSH in ELF was not significantly different in HIV-seropositive individuals compared with normal subjects (628.1 +/- 63.9 microM versus 499.9 +/- 86.0 microM, p = 0.38). However, there was a significantly higher concentration of ELF GSH in HIV-seropositive cigarette smokers (n = 30) compared with nonsmokers (n = 29) (800.3 +/- 107.7 microM versus 443.6 +/- 45.3 microM, p = 0.004). The percentage of total GSH in the oxidized form (GSSG) was similar in both the HIV-seropositive and the normal subject groups (3.4 +/- 0.3% versus 3.0 +/- 0.4%, p = 0.559). There were no significant correlations between ELF GSH or GSSG concentrations and age, CD4 count, or pulmonary function. There was, however, a significant negative correlation between BAL lymphocyte percentage and GSH. The current study suggests that for those patients whose HIV infection is at a relatively early phase, the levels of GSH in the lung ELF are normal.

Adult↗
PubMed1997

Bovine surfactant therapy for patients with acute respiratory distress syndrome.

Lung surfactant is deficient in patients with acute respiratory distress syndrome (ARDS). We performed a randomized, prospective, controlled, open-label clinical study of administration of a bovine surfactant to patients with ARDS to obtain preliminary information about its safety and efficacy. Patients received either surfactant by endotracheal instillation in addition to standard therapy or standard therapy only. Three different groups of patients receiving surfactant were studied: patients receiving up to eight doses of 50 mg phospholipids/kg, those receiving up to eight doses of 100 mg phospholipids/kg, and those receiving up to four doses of 100 mg phospholipids/kg. Outcome measures included ventilatory support parameters, arterial blood gases, organ system failures, bronchoalveolar lavage (BAL) analyses, immunologic analyses, survival, and adverse events during the 28-d study period. Fifty-nine study patients were evaluable; 43 in the surfactant group and 16 in the control group. The FI(O2) at 120 h after treatment began was significantly decreased only for patients who received up to four doses of 100 mg phospholipids/kg surfactant as compared with control patients (p = 0.011). Mortality in the same group of patients was 18.8%, as compared with 43.8% in the control group (p = 0.075). The surfactant instillation was generally well tolerated, and no safety concerns were identified. This pilot study presents preliminary evidence that surfactant might have therapeutic benefit for patients with ARDS, and provides rationale for further clinical study of this agent.

Adult↗
PubMed1997

Alveolar fluid glutathione decreases in asymptomatic HIV-seropositive subjects over time.

BACKGROUND: Initial investigations demonstrated a deficiency of glutathione (GSH) in the epithelial lining fluid (ELF) of HIV-seropositive patients. In a recent study, our laboratory was unable to document such a deficiency. The current study was performed in an attempt to reconcile those disparate findings. STUDY OBJECTIVES: To determine if ELF GSH decreases over time in asymptomatic HIV-seropositive subjects. DESIGN: Prospective, longitudinal study. SETTING: Major university medical center. PATIENTS OR PARTICIPANTS: Thirty-three asymptomatic HIV-seropositive volunteers. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: BAL was performed on 33 asymptomatic HIV-seropositive subjects at baseline, 6 months later, and 12 months later. The volume of ELF and the concentration of GSH and oxidized GSH were determined. The concentration of total GSH in ELF was 689.0+/-100.4 microM. This significantly decreased when measured 6 and 12 months later (355.9+/-41.7 microM, and 397.9+/-52.7 microM, respectively, p=0.01, compared with baseline, both comparisons). Significant decreases were also noted in the HIV-seropositive subjects who smoked cigarettes (baseline--762.6+/-142.4 microM; 6 months--373.7+/-45.9 microM; 12 months--459.3+/-73.8 microM, p<0.03, for baseline vs 6 months, and baseline vs 12 months). In nonsmoking HIV-seropositive subjects, there was a decrease in ELF GSH over time, but it did not reach statistical significance (baseline--589.1+/-138.2 microM; 6 months--335.3+/-74.1 microM; 12 months--345.8+/-74.0 microM, p>0.1, all comparisons). The percentage of total GSH in the oxidized form was similar at all three time points (baseline--3.8+/-0.5%; 6 months--3.1+/-0.5%; 12 months--3.9+/-0.9%, p>0.1, all comparisons). CONCLUSIONS: The current study demonstrates that the GSH level in ELF is significantly decreased in HIV-seropositive subjects 6 and 12 months after the initial determination.

Adult↗
PubMed1996

High-dose furosemide alters gas exchange in a model of acute lung injury.

PURPOSE: Furosemide is often used to reduce edema in patients with acute respiratory distress syndrome (ARDS). It was hypothesized that furosemide would reduce lung water and improve gas exchange in a phorbol-myristate acetate (PMA) model of acute lung injury. METHODS: Two groups of mongrel dogs received PMA (25 to 30 micrograms/kg) and continuous saline at 10 mL/kg/h; one group received PMA plus two 1-mg/kg doses of furosemide at 1 and 2 hours after PMA. Arterial blood gases on F1O2 = 1.0 and double-dilution lung water were measured at intervals over 7 hours. RESULTS: In dogs receiving PMA+furosemide, AaDO2 and shunt fraction increased compared with dogs receiving PMA only (AaDO2, P = .014; shunt, P = .017). There were no significant differences between the groups in lung water (P = .34) during the experiment or in wet/dry weight postmortem. Urine flow was markedly reduced in both groups; the kidneys appeared unresponsive to the diuretic effects of furosemide. Significant elevations in hematocrit and pulmonary vascular resistance were seen in furosemide-treated compared with PMA-only dogs. CONCLUSIONS: In this model of ARDS, which results in the absence of effective kidney function and multiple organ failure, furosemide compromises alveolar-capillary gas exchange and fails to influence the time course of lung water accumulation. The results suggest that the nondiuretic affects of furosemide cannot explain its purported clinical utility in ARDS.

Animals↗
PubMed1996

Consensus on surfactant and inhaled nitric oxide for ARDS.

Adult respiratory distress syndrome (ARDS) remains a major problem in intensive care medicine. While the triggers are not well understood, the process often involves generalized neutrophil activation and sequestration in the lung which initiate inflammatory cascades. These effects can be localized to the pulmonary tissues as well as diffusely throughout the body. Should the latter occur, the patient presents with multiple organ failure (MOF). Attempts to interfere with this series of events have included replacement therapy for surfactant and its components because of observations that the natural surfactant mechanisms are impaired or damaged. The effectiveness of replacement therapy has been tested in various protocols involving synthetic composites and animal (bovine) surfactants. While major differences in protocol design have led to conflicting results, there appears to be evidence that installation of bovine surfactant can reduce mortality in ARDS. A major limitation in adult therapeutics utilizing surfactant is the method of delivery; direct instillation utilizes large quantities, thus limiting its availability. Aerosolized therapy may have promise if smaller amounts delivered by this modality are more effective. Inhaled nitric oxide may also have therapeutic potential in ARDS. By improving ventilation perfusion mismatch, ventilatory requirements can be reduced.

Administration, Inhalation↗
PubMed1996

Alpha 1-antitrypsin deficiency: evaluation of bronchiectasis with CT.

PURPOSE: To assess bronchiectasis depicted with computed tomography (CT) in patients with alpha 1-antitrypsin deficiency and to examine associated clinical correlates. MATERIALS AND METHODS: CT scans in 14 patients with alpha 1-antitrypsin deficiency were evaluated by two thoracic radiologists for the presence and extent of bronchiectasis and emphysema. The findings were correlated with numeric infection scores on the basis of symptoms of sputum production and respiratory infection and with a history of conditions that may predispose to development of bronchiectasis. RESULTS: Six (43%) of 14 patients had CT evidence of bronchiectasis. Patients with bronchiectasis had significantly higher infection scores than did patients without bronchiectasis (P < .005). Two patients had diffuse cystic bronchiectasis, and neither reported a history of illness that may have predisposed them to this condition. CONCLUSION: Bronchiectasis may be more common in patients with alpha 1-antitrypsin deficiency than has been previously recognized. The diagnosis of alpha 1-antitrypsin deficiency should be considered in patients with emphysema and diffuse cystic bronchiectasis.

Bronchiectasis↗
PubMed1995

Monocyte Fc gamma receptor cross-linking induces IL-8 production.

In response to bacterial cell wall products such as LPS, monocytes produce IL-8, a powerful neutrophil chemotaxin. However, in the absence of bacterial pathogens, immune complex-mediated diseases such as rheumatoid arthritis are associated with high levels of IL-8 in monocyte-rich compartments. Since it is known that IgG-containing immune complexes can recruit neutrophils via an Fc gamma R-dependent process, we hypothesized that cross-linking of monocyte Fc gamma receptors may induce IL-8. To test this hypothesis, peripheral blood mononuclear cells were evaluated for IL-8 induction in response to immobilized LPS-free pooled human IgG. Immobilized IgG, but not soluble IgG, induced IL-8 in a dose-dependent manner (p < 0.05, r = 0.99). This induction corresponded with an up-regulation in IL-8 steady state mRNA levels that peaked at 4 h. The released IL-8 was functional, since supernatants induced concentration-dependent neutrophil migration that was inhibited by a monoclonal anti-IL-8 Ab. Evaluation of purified monocytes for IL-8 production, as well as FACS analysis of IgG-stimulated PBMC preparations, demonstrated that monocytes are the principal IL-8 producer cell. Thus, monocyte Fc gamma R cross-linking induces biologically active IL-8, which may participate in the pathogenesis of immune complex-mediated diseases.

Cells, Cultured↗
PubMed1993

Chronic obstructive pulmonary disease: less common causes--an algorithm for the primary care physician.

The clinical features and distinguishing characteristics of the less common causes of chronic airflow obstruction have been reviewed. Clearly, the majority of patients have cigarette-induced chronic bronchitis and/or emphysema. However, for those patients with chronic airflow obstruction who are younger than 40 years old and/or have no or modest (less than 20 pack-years) smoking histories, a detailed assessment is warranted. A logical approach to the evaluation of the patient with dyspnea and chronic airflow obstruction has been outlined, with the goal of identifying those patients with potentially reversible disease, and to underscore the fact that not all "COPD" is due to cigarette smoking.

Adult↗
PubMed1992

Adverse effects of neutrophils on the lung.

Studies of both emphysema and adult respiratory distress syndrome (ARDS) support the premise that lung injury is due to unregulated host defense mechanisms. A major mediator of host defense and injury is the neutrophil, which is relatively incapable of regulating its own function. Accordingly, defects in regulatory mechanisms allow neutrophils to damage the lungs. Emphysema serves as a prime example of this link between host defense and injury. Hereditary emphysema is caused by a deficiency in alpha 1-antitrypsin (alpha 1-AT), a protease inhibitor. The decreased levels of this enzyme in affected individuals result in inadequate protection against neutrophil elastase and other proteolytic enzymes, leading to lung damage. Patients with acquired emphysema, associated with cigarette smoking, have normal levels of alpha 1-AT in their lungs. However, the alpha 1-AT in these patients has a reduced ability to associate with and inhibit the action of neutrophil elastase. Thus, both types of emphysema involve an alteration in the balance between proteases and antiproteases. The lung damage observed in patients with ARDS also appears to involve neutrophils, but in this case elastase may not be the culprit. In these patients, neutrophil elastase appears to be inactivated by high levels of alpha 1-AT, thus preventing excess protease action. It is hoped that a more complete understanding of the mechanisms involved in host defense and injury will enable the development of specific therapeutic interventions, such as the alpha 1-AT replacement therapy that is being used to treat patients with hereditary emphysema.

Emphysema↗
PubMed1991

Initial recruitment of neutrophils to alveolar structures in acute lung injury.

The adult respiratory distress syndrome and bacterial pneumonia are both characterized by an influx of neutrophils into the lung. The neutrophil has been implicated as having a "pathological" role in adult respiratory distress syndrome, in contrast to its role in bacterial pneumonia. We hypothesized that processes resulting in neutrophil recruitment to the lung are distinct, depending on whether the inflammatory stimulus arises in the intravascular or the alveolar compartment of the lung. Anesthetized sheep with lung lymph fistulas were utilized to access the three compartments of the lung relevant to studies of transpulmonary neutrophil migration. Serum, lung lymph, and bronchoalveolar lavage fluid were studied for neutrophil influx and chemotactic activity before and after administration of endotoxin by either an intravascular or inhaled alveolar route. Both groups developed significant neutrophil influx into the lymph and bronchoalveolar lavage fluid by 3 h postendotoxin. Those animals receiving intravascular endotoxin developed chemotactic gradients opposing neutrophil migration into the lung in contrast to animals receiving alveolar endotoxin, suggesting that neutrophil influx into the lung occurs by random migration.

Animals↗
PubMed1990

The protease-antiprotease balance within the human lung: implications for the pathogenesis of emphysema.

Critical elements of the mechanisms of emphysema remain to be clarified. However, taken together, the existing evidence supports the concept that alveolar matrix destruction ensues as the regulatory interplay between oxidant and protease expression is subverted. The final common pathway of matrix destruction links the inherited and acquired forms of emphysema through the ultimate expression of unimpeded neutrophil elastase.

Animals↗
PubMed1990

Analysis of airflow obstruction by bronchoalveolar lavage following bone marrow transplantation. Implications for pathogenesis and treatment.

The development of airflow obstruction, most often due to bronchiolitis, is a significant cause of morbidity and mortality in recipients of allogeneic BMT. Current consensus holds that this airways disease is the result of chronic GVHD and/or CMV infection. However, recent studies of idiopathic forms of BRO have demonstrated a striking influx of neutrophils into the lungs of affected individuals. Reasoning that the immune cell populations involved in tissue injury associated with either CGVHD or CMV infection would consist predominantly of lymphocytes, we tested this hypothesis by performing BAL in 12 adults with minimal or absent smoking histories who developed significant airflow obstruction (FEV1/FVC = 80.7 +/- 1 percent preBMT and 56.8 +/- 2.4 percent postBMT; p less than 0.001) following allogeneic BMT. Eleven of 12 patients had evidence of chronic, stable GVHD at the time of the study. In contrast to non-BMT patients with BRO, BAL defined two distinct patterns of lung inflammation in the BMT patients with airflow obstruction: (a) neutrophil predominance (five patients; neutrophil percentage = 20.2 +/- 6.6 percent); and (b) lymphocyte predominance (three patients; lymphocyte percentage = 35.9 +/- 12.1 percent). These data suggest that the pattern of inflammation in the lungs of BMT patients with BRO is not uniform and is not associated with active microbial infection. From these results, it is inferred that the airways injury in BMT patients may reflect diverse pathogenetic mechanisms initiated in the context of CGVHD and cytotoxic drug therapy.

Adult↗
PubMed1990

Multiple organ failure.

Diagnostic criteria for individual organ system failure are imprecise, a factor that adds a considerable amount of ambiguity to this area of clinical research. Nonetheless, multiple organ failure is a common sequela of ARDS and other catastrophic medical and surgical illnesses that continues to limit patient survival. The cumulative weight of investigative evidence currently supports the premise that concepts of acute respiratory failure must encompass the abnormal gas exchange in the systemic as well as the pulmonary microvasculature. In this context, we need not dispense with the term ARDS, as respiratory distress applies equally to the nonpulmonary organs as well as the lungs.

Bacterial Infections↗
PubMed1989

Acute eosinophilic pneumonia as a reversible cause of noninfectious respiratory failure.

Although chronic eosinophilic pneumonia is a well-known disorder, acute eosinophilic pneumonia has not been as well characterized. We describe the clinical features, results of bronchoalveolar lavage, and follow-up studies of four patients with acute eosinophilic pneumonia. The patients presented with an acute febrile illness, severe hypoxemia (partial pressure of arterial oxygen less than 60 mm Hg), diffuse pulmonary infiltrates, an increased number of eosinophils (mean +/- SEM, 42 +/- 4.8 percent) in bronchoalveolar-lavage fluid, and an absence of infection and previous atopic illness. The illness resolved rapidly after treatment with erythromycin and corticosteroids. The patients received doses of oral prednisone that were tapered over 10 days to 12 weeks, and none have relapsed since the steroids were discontinued. After a minimum follow-up period of five months, clinical evaluation, chest radiography, and pulmonary-function tests have shown no residual abnormalities attributable to the acute eosinophilic pneumonia. Follow-up bronchoalveolar lavage has demonstrated less than or equal to 1 percent eosinophils in all patients. We believe that we are describing an acute form of eosinophilic lung disease distinct from previously described syndromes. It can be diagnosed by bronchoalveolar lavage and seems to respond to treatment with corticosteroids.

Acute Disease↗
PubMed1989

Bronchiolitis in adults. A reversible cause of airway obstruction associated with airway neutrophils and neutrophil products.

In the past 4 yr, 16 adult patients were identified who had accelerated onset of a severe respiratory disorder (usually obstructive in nature) that was clinically distinct from the more commonly encountered chronic obstructive disorders (e.g., chronic bronchitis, emphysema, asthma, bronchiectasis, cystic fibrosis, and alpha 1-antitrypsin deficiency). These patients, termed patients with "bronchiolitis," underwent pulmonary function testing, bronchoscopy with bronchoalveolar lavage (BAL), and open lung biopsy. Although lung biopsy findings varied somewhat among the patients, each biopsy contained a prominent component of bronchiolitis. Pulmonary function testing and BAL were also repeated after 3 months of treatment with oral prednisone (1 mg/kg/day). Initial BAL neutrophil percentages were significantly higher in the bronchiolitis group (54 +/- 10%) than in smokers with chronic bronchitis (3.9 +/- 1.0%) or in normal nonsmoking volunteers (0.8 +/- 0.5%) (p less than 0.01, both comparisons). Eleven of 15 patients with bronchiolitis had significant improvement (greater than or equal to 15% increase in FEV1) in their lung function after prednisone treatment. Furthermore, this "responder" subgroup had a significant reduction in BAL neutrophil percentages after treatment with prednisone (46 +/- 15% to 6 +/- 3%, p less than 0.05). Finally, the neutrophil products collagenase and myeloperoxidase were detected in the BAL fluid of patients with bronchiolitis. These findings suggest a central role for the neutrophil in the pathogenesis of bronchiolitis and emphasize the utility of BAL in the identification of these patients.

Adolescent↗