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A F Suffredini

Publications and source records attributed to A F Suffredini.

At least 37 records · Page 2Linked to original sources
PubMed1994

Human polymorphonuclear leukocytes lack detectable nitric oxide synthase activity.

Nitric oxide regulates polymorphonuclear leukocyte (PMN) function, but whether or not human PMNs express nitric oxide synthase (NOS) activity is controversial. We studied NOS activity in human PMNs by using human aortic endothelial cells (HAECs) for comparison. The conversion of L-arginine to L-citrulline, a relatively specific measure of NOS activity, was easily measured and inducible in fractionated HAECs, and > 90% of all L-arginine conversion was blocked by the NOS inhibitor, N omega-amino-L-arginine (L-NAA). In fractionated PMNs, L-arginine conversion was low and was unaffected by L-NAA. In addition, NOS activity was not induced in PMNs by LPS, IL-1 beta, or IFN-gamma. In a whole-cell assay, total L-arginine conversion was much lower in human PMNs compared with HAECs (3.38 +/- 0.21 vs 157.5 +/- 10.28 pmol/h/10(6) cells, respectively; p < 0.01). This conversion in whole PMNs was not increased in vitro by LPS, IFN-gamma, IL-1 beta, or TNF-alpha nor decreased by W13, a calmodulin inhibitor. Furthermore, PMNs isolated from four volunteers before and after challenge with i.v. LPS (4 ng/kg) showed no increase in L-arginine to L-citrulline conversion. Nitrite and nitrate release from human PMNs was 35-fold lower than for HAECs and was not inhibited by L-NAA. These data suggest that human PMNs do not express NOS activity.

Amino Acid Oxidoreductases↗
PubMed1994

Selected treatment strategies for septic shock based on proposed mechanisms of pathogenesis.

PURPOSE: To review selected new therapies for septic shock designed to inhibit bacterial toxins or endogenous mediators of inflammation. DATA SOURCES: Scientific journals, scientific meeting proceedings, and Food and Drug Administration advisory committee proceedings. STUDY SELECTION AND EXTRACTION: Preclinical and clinical data from trials using core-directed antiendotoxin antibodies and anticytokine therapies for sepsis and studies in animal models of sepsis from our laboratory. RESULTS OF DATA SYNTHESIS: Ten clinical trials using core-directed antiendotoxin antibodies produced inconsistent results and did not conclusively establish the safety or benefit of this approach. Both anti-interleukin-1 and anti-tumor necrosis factor (TNF) therapies have been beneficial in some animal models of sepsis but did not clearly improve survival in initial human trials, and one anti-TNF therapy actually produced harm. Neutrophils, another target for therapeutic intervention, protect the host from infection but may also contribute to the development of tissue injury during sepsis. In a canine model of septic shock, granulocyte colony-stimulating factor increased the number of circulating neutrophils and improved survival, but an anti-integrin (CD11/18) antibody that inhibits neutrophil function worsened outcome. Nitric oxide, a vasodilator produced by the host, causes hypotension during septic shock but may also protect the endothelium and maintain organ blood flow. In dogs challenged with endotoxin, the inhibition of nitric oxide production decreased cardiac index and did not improve survival. CONCLUSIONS: No new therapy for sepsis has shown clinical efficacy. Perhaps more accurate clinical and laboratory predictors are needed to identify patients who may benefit from a given treatment strategy. On the other hand, the therapeutic premises may be flawed. Targeting a single microbial toxin such as endotoxin may not represent a viable strategy for treating a complex inflammatory response to diverse gram-negative bacteria. Similarly, the strategy of inhibiting the host inflammatory response may not be beneficial because immune cells and cytokines play both pathogenic and protective roles. Finally, our scientific knowledge of the complex timing of mediator release and balance during sepsis may be insufficient to develop successful therapeutic interventions for this syndrome.

Animals↗
PubMed1994

Endotoxin administration to humans primes alveolar macrophages for increased production of inflammatory mediators.

To elucidate potential mechanisms of the acute lung injury associated with endotoxemia, we evaluated the effect of intravenously administered endotoxin on the ability of alveolar macrophages isolated by bronchoalveolar lavage from normal subjects to produce inflammatory mediators. Within 1 hr of endotoxin (4 ng/kg body weight) administration, all 12 study subjects developed constitutional symptoms and leukopenia, and within 3 hr, low-grade fever. Resolution of symptoms and fever by 6 hr was accompanied by systemic granulocytosis. Although intravenously administered endotoxin appeared to activate a subset of circulating monocytes, it did not alter the bronchoalveolar lavage cell number, phenotype (95% macrophages), or constitutively expressed high levels of surface HLA-DR and O2-. In contrast, intravenous endotoxin primed the alveolar macrophages for enhanced lipopolysaccharide-induced secretion of interleukin-1 (11.8 to 25.8 U/ml; P = 0.04), tumor necrosis factor-alpha (titer, 6.8 to 13.6; P = 0.20), and prostaglandin E2 (38.4 to 116.3 ng/ml; P = 0.035). These results demonstrate that low-dose intravenous endotoxin primes human alveolar macrophages, which are already differentiated in situ, for enhanced secretion of inflammatory mediators. Such mediators may contribute to the pulmonary changes associated with endotoxemia and acute lung injury.

Adult↗
PubMed1994

Current prospects for the treatment of clinical sepsis.

OBJECTIVES: To review the role of antimediator therapy in the inflammatory cascade associated with sepsis, and to review the status of animal and clinical studies being conducted on novel therapies for septic shock. DATA SOURCES: Information presented at the 22nd Educational and Scientific Meeting of the Society of Critical Care Medicine on June 9-13, 1993 in New York City was reviewed, along with supportive documentation from the English language literature. STUDY SELECTION: Controlled animal studies that provide evidence for the effectiveness of antiendotoxin and anticytokine therapies. The preliminary results of selected clinical trials are also presented. DATA EXTRACTION: This review focuses on data describing the potential role of mediator antagonists in the treatment of septic shock. DATA SYNTHESIS: Information concerning the effectiveness and tolerability of these therapies has been integrated into a description of emerging therapies for septic shock. CONCLUSIONS: Clinical trials of antiendotoxin antibodies have not shown them to have therapeutic benefit. New agents that neutralize or antagonize the cellular effects of endotoxin may provide an alternative means to inhibit endotoxin effects during severe Gram-negative infections. Anti-interleukin-1 and antitumor necrosis factor-alpha therapies have demonstrated efficacy in animal models, but the results have been inconsistent in human trials. Preliminary results from clinical trials of cytokine antagonists suggest that these therapies may be effective in the most severely ill patients. Further clinical trials will be required to determine the therapeutic role of these agents in septic shock.

Animals↗
PubMed1993

Neutrophil attractant protein-1 and monocyte chemoattractant protein-1 in human serum. Effects of intravenous lipopolysaccharide on free attractants, specific IgG autoantibodies and immune complexes.

We recently found that normal human sera contain IgG antibodies against two chemoattractants, neutrophil attractant protein-1 (NAP-1/IL-8) and monocyte chemoattractant protein-1 (MCP-1), as well as immune complexes of these proteins. Intravenously administered LPS was reported to cause a sharp rise in serum NAP-1 concentration. Our study was designed to determine if LPS also caused an increase in MCP-1 and to measure associated changes in concentrations of antibody and immune complex. LPS caused a rise to peak within 2 to 3 h in serum concentrations of free NAP-1 and MCP-1, followed by an almost equally rapid fall toward base-line levels by about 5 h postinjection. MCP-1 concentration in sera from the 11 subjects rose to a peak of 330 +/- 52 pM. The peak value for NAP-1 was 80 +/- 11 pM. In 10 of the 11 subjects, free IgG autoantibody to MCP-1 decreased from a mean pre-LPS value of 1820 +/- 660 pM to a mean low of 53% of the respective initial values. Corresponding data for IgG anti-NAP-1 were a pre-LPS concentration of 216 +/- 7 pM, which decreased to a mean low of 44% of the respective initial values. The finding in some subjects of a rapid rise in free antibody after the nadir suggests the possibility of acute regulation of autoantibody secretion rates. Although the results suggested that LPS-induced chemoattractant combined with free antibody, serum concentrations of MCP-1-IgG or NAP-1-IgG did not increase, which points to an as yet unknown mechanism for trapping and elimination of the immune complexes.

Adult↗
PubMed1993

Activation of the kallikrein-kinin system after endotoxin administration to normal human volunteers.

The objective of this study was to determine the role of the kallikrein-kinin system in healthy humans after intravenous administration of either Escherichia coli endotoxin or saline. We studied a total of 18 healthy nonsmoking volunteers, 23 to 38 years old, in an open-label study at the Critical Care Medicine Department, Clinical Center, National Institutes of Health (Bethesda, MD) in which some of the patients served as their own controls. After baseline data collection, the subjects received intravenously either E coli endotoxin (n = 15, 4 ng/kg of body weight) or saline (n = 8, controls). Signs, symptoms, systemic blood pressure, factor XII, plasma prekallikrein (PK), factor XI (FXI), antithrombin III (AT-III), high molecular weight kininogen (HK), and alpha 2-macroglobulin-kallikrein complexes were measured at baseline and 1, 2, 3, 5, and 24 hours after injection of either saline or endotoxin. After infusion of endotoxin, we found the functional plasma levels of FXI decreased at 2 hours (P < .05) and at 5 hours (P < .05). Functional PK was significantly depressed by 2 hours (P < .05), at 5 hours (P < .05), and at 24 hours (P < .01), whereas the PK antigen was only low at 5 hours (P < .05). These changes were accompanied by a significant increase in circulating alpha 2-macroglobulin-kallikrein complexes at 3 hours (P < .05) and 5 hours (P < .01). No significant changes occurred in the plasma levels of factor XII or HK. We concluded that clinical response to intravenous endotoxin in healthy human volunteers is associated with activation of the kallikrein-kinin systems. Further investigation is needed with specific inhibitors of the kallikrein-kinin system to define its primary or secondary role in the endotoxin-mediated reactions.

Adult↗
PubMed1993

Response of man to endotoxin.

Endotoxin, a cell wall component of Gram-negative bacteria, plays a central role in the pathogenesis of septic shock. By administering small doses of intravenous endotoxin to humans, a variety of acute inflammatory responses are induced which are qualitatively similar to those that occur during the early stages of septic shock. Within hours of the administration of intravenous endotoxin to human volunteers, changes occur in systemic hemodynamics, ventricular function, pulmonary gas exchange and permeability. In conjunction with these changes in organ function, a wide variety of inflammatory mediators are released which appear to contribute to these responses. These include the release of proinflammatory cytokines (e.g. tumor necrosis factor-alpha, IL-1 beta, IL-6, IL-8), activation of the fibrinolytic system, kallikrein-kinin generation and phospholipase A2 release. Phagocytic leukocytes are primed for enhanced inflammatory responses following endotoxin administration. Counter-regulatory responses are initiated in parallel and may serve to limit some of the end-organ responses by the inflammatory mediators. This human model provides a unique opportunity to extend previous concepts of acute inflammation and to evaluate the earliest responses activated after exposure to an important bacterial component. Defining the pathways and responses initiated during acute human endotoxemia may allow a better understanding of host responses that are critical to the development of organ dysfunction and shock due to severe infections.

Cytokines↗
PubMed1993

Leukocyte CD18 monoclonal antibody worsens endotoxemia and cardiovascular injury in canines with septic shock.

We investigated the effects of a murine monoclonal antibody directed against the canine leukocyte CD11/18 adhesion complex (MAb R15.7) in a canine model of septic shock. Awake 2-yr-old purpose-bred beagles were studied 7 days before and 1, 2, 4, and 10 days after intraperitoneal placement of an Escherichia coli-infected fibrin clot. Starting 12 h before clot placement, animals received 0.5-1 mg/kg iv every 12 h (4 doses total) of either MAb R15.7 (MAb group, n = 8) or, as controls, murine serum protein (n = 8). After infected clot placement, all animals received antibiotic (ceftriaxne, 100 mg.kg-1.day-1 for 4 days). Two of eight control animals and four of eight MAb animals died (P = 0.4). During the first 8 h after clot placement, MAb animals, compared with control animals, had greater (P < 0.06) increases in serum endotoxin levels and higher (P < 0.05) neutrophil counts. Day 1 after clot placement, MAb animals, compared with control animals, had decreased (P < 0.05) central venous pressure and arterial pH and increased (P < 0.05) arterial lactate. Day 2 after clot placement, MAb animals, compared with control animals, had decreased (P < 0.05) cardiac index and mean arterial pressure. In summary, MAb R15.7, although associated with increased neutrophil counts, worsened serum endotoxemia, acidosis, and cardiovascular function in this canine model of septic shock. These data suggest that in septic shock, antibody directed against this leukocyte membrane protein complex may be harmful, possibly via impairment of normal leukocyte function.

Acid-Base Equilibrium↗
PubMed1993

Compartmentalization of the acute cytokine response in humans after intravenous endotoxin administration.

Lung cytokine production was examined after the intravenous administration of endotoxin to 23 normal human subjects. Bronchoalveolar lavage (BAL) was performed 7 days before and 1.5 or 5 h after endotoxin (4 ng/kg). Cytokine mRNA was evaluated in cell pellets (> 98% macrophages) by use of reverse transcription and the polymerase chain reaction. Immunoreactivity was measured by enzyme-linked immunosorbent assay of 20- to 40-fold concentrated BAL. Interleukin- (IL) 8 was detected in BAL (4-130 pg/ml) but not in the serum at baseline. Few neutrophils were found in BAL (< 1%) despite this IL-8 gradient. Peak serum IL-8 levels occurred 2 h after endotoxin (3,930 +/- 241 pg/ml), but BAL neutrophils and IL-8 did not increase. Peak serum tumor necrosis factor (TNF) levels occurred 1.5 h after endotoxin (1,844 +/- 210 pg/ml), but TNF was detected in only 1 of 20 BAL samples. TNF and IL-8 mRNA were detected by polymerase chain reaction in > 70% of the BAL samples before endotoxin, whereas IL-1 alpha, IL-1 beta, and IL-6 were detected in < 25% of the BAL samples. After endotoxin, no change was detected in cytokine mRNA expression. Actinomycin D treatment of the BAL did not alter the pattern of cytokine mRNA expression. These data suggest that mechanisms exist to insulate the alveolar space from the stimulatory effects of endotoxin and high circulating levels of cytokines. Additional factors appear to control the chemotactic effects of IL-8 on neutrophils in the air spaces during acute systemic inflammation.

Actins↗
PubMed1992

NIH conference. Respiratory disease in the immunosuppressed patient.

Pulmonary complications, both infectious and noninfectious, are an important cause of morbidity in patients with various types of immunosuppression. The appropriate response to these clinical problems requires an understanding of pulmonary host defense and of the various types of systemic immunosuppression. Infectious and noninfectious pulmonary complications may vary according to the type of immunosuppression as well as to the degree and duration of immunosuppression. Appropriate clinical management also requires an understanding of the clinical problems commonly seen in specific groups of immunosuppressed patients and an understanding of the sensitivity, specificity, and potential complications associated with the available diagnostic approaches to those patients. Because respiratory disease in these patient groups may progress rapidly to respiratory failure, an expeditious evaluation based on the knowledge of likely causes of respiratory disease and prompt specific or empiric therapy are indicated. Specific sets of algorithms for the evaluation of both focal and diffuse pulmonary disease may facilitate such an evaluation. In addition, an aggressive approach to the prevention of pulmonary disease including immunization, prophylaxis, and immunomodulation (for example, colony stimulating factors) may be warranted in specific subgroups at risk.

Algorithms↗
PubMed1992

Lymphoid pneumonitis in 50 adult patients infected with the human immunodeficiency virus: lymphocytic interstitial pneumonitis versus nonspecific interstitial pneumonitis.

Lymphocytic interstitial pneumonitis (LIP) and nonspecific interstitial pneumonitis (NIP) are pulmonary complications of human immunodeficiency virus (HIV) infection that occur in the absence of a detectable opportunistic infection or neoplasm. We reviewed lung biopsy specimens from 50 adult HIV-infected patients, of whom four had LIP and 46 had NIP. The majority (47 of 50) of specimens from patients with NIP showed mild chronic interstitial pneumonitis (CIP/NIP), with three showing features of diffuse alveolar damage, organizing phase. In contrast to CIP/NIP, the five specimens from four patients with LIP demonstrated more extensive lymphocytic interstitial infiltrates that extended into the alveolar septal interstitium. The majority of the interstitial lymphocytes in both NIP and LIP were of T-cell origin and stained for UCHL-1. The etiologies of NIP and LIP remain unknown. Since the common opportunistic infections were excluded by routine methods, we sought, with special techniques, to investigate whether HIV, Epstein-Barr virus (EBV), or cytomegalovirus (CMV) could be identified in lung biopsy specimens from these patients. By in situ hybridization, we found one LIP specimen with expression of large amounts of HIV RNA primarily within macrophages in germinal centers; in the remaining specimens, occasional cells expressing HIV RNA were found (two LIP and four NIP). Neither CMV nor EBV was found by in situ hybridization in seven specimens; in these same specimens EBV was detected using the polymerase chain reaction in only one case of NIP, similar to results in control specimens. These results, together with the knowledge that lymphocytic pulmonary lesions may be caused by lentiviruses in humans and animals, suggest that HIV plays a significant role in the pathogenesis of both NIP and LIP in adult HIV-infected patients; in contrast, our data do not demonstrate a direct role for either EBV or CMV.

Adult↗
PubMed1992

Effects of ibuprofen and pentoxifylline on the cardiovascular response of normal humans to endotoxin.

Endotoxin is a major mediator of the life-threatening cardiovascular dysfunction that characterizes Gram-negative sepsis. In animal models of endotoxemia, pretreatment with ibuprofen or pentoxifylline attenuates some of these cardiovascular changes. To evaluate the effects of these agents on the human cardiovascular response to endotoxemia, hemodynamic variables were measured serially in 24 normal subjects who were given intravenous endotoxin. The subjects were randomized to receive oral ibuprofen (n = 9), pentoxifylline (n = 10), or no medication before endotoxin administration (n = 5). The subjects were volume loaded 3-5 h after endotoxin administration, and hemodynamic measurements were reassessed. Core temperature after endotoxin alone or endotoxin-pentoxifylline approached a maximum at 3 h (greater than or equal to 38.6 degrees C), while the endotoxin-ibuprofen group remained afebrile. At 3 and 5 h, all three groups had significant increases in heart rate, cardiac index, oxygen delivery, and oxygen consumption, while systemic vascular resistance index decreased significantly from baseline. The oxygen extraction ratio remained unchanged. After volume loading, the left ventricular ejection fraction and left ventricular end-diastolic and end-systolic volume indexes did not differ among the groups. The hyperdynamic cardiovascular response to endotoxin in humans occurs in the absence of fever and is not significantly ameliorated by oral cyclooxygenase or phosphodiesterase inhibition.

Adult↗
PubMed1992

Pulmonary and oxygen transport effects of intravenously administered endotoxin in normal humans.

Little data are available describing the initial changes in pulmonary function and oxygen transport during human endotoxemia. We studied 26 normal humans after intravenously administered endotoxin (4 ng/kg). To evaluate alterations in gas exchange, hemodynamic monitoring was performed in nine subjects given endotoxin and six subjects given saline only. Compared with the control subjects, no changes in gas exchange occurred at 3 h, but after volume loading (mean, 2.2 L saline infused from 3 to 5 h) the PaO2 fell (86.1 +/- 2.3 mm Hg, p = 0.042), and the AaPO2 widened (18.5 +/- 1.7 mm Hg, p = 0.005). Oxygen consumption and delivery both increased significantly at 3 h (219 +/- 17 and 1,030 +/- 43 ml/min.min2) and 5 h (203 +/- 7 and 949 +/- 48 ml/min.min2) (p less than or equal to 0.035), whereas oxygen extraction fell at 3 h (p = 0.041). Seventeen subjects underwent bronchoalveolar lavage 14 +/- 4 days before and at 1.5 to 3 h (n = 8) or 5 h after (n = 9) the administration of endotoxin. No increase in the total number of cells or percent or absolute number of neutrophils was found at either time point. The rate of clearance of inhaled 99mTc-diethylenetriamine pentacetate aerosol, a measure of alveolar epithelial permeability, increased in subjects scanned before 3 h (n = 8; p less than 0.05), whereas no significant changes occurred in subjects scanned 5 h after endotoxin (n = 5) or in control subjects (n = 6). Early inflammatory responses after intravenous administration of endotoxin to normal humans results in alterations in gas exchange and lung permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Reduction of pulmonary surfactant in patients with human immunodeficiency virus infection and Pneumocystis carinii pneumonia.

We assessed qualitative and quantitative differences in surfactant lipid composition of bronchoalveolar lavage (BAL) fluid in patients with acquired immune deficiency syndrome (AIDS) and Pneumocystis carinii (PC) pneumonia. Five normal volunteers and 27 patients with human immunodeficiency virus (HIV) infection underwent BAL for evaluation of possible pulmonary infection. Bronchoalveolar lavage studies in eight patients were negative for PC organisms, and 19 were positive. Pneumocystis carinii pneumonia was graded (mild vs moderate to severe) by initial alveolar-arterial oxygen gradient. Bronchoalveolar lavage fluid was centrifuged, the lipids were extracted from the supernatant, and total lipid profiles of dephosphorylated glycerolipids were analyzed as trimethylsilylether derivatives by high temperature gas-liquid chromatography. Phospholipase A2 levels were determined using a radiolabeled E coli membrane method. Compared to the normal volunteers (109 +/- 13 micrograms/5 ml) and the PC negative group (107 +/- 13 micrograms/5 ml), total BAL lipid was reduced for both the mild PC pneumonia group (73 +/- 10 micrograms/5 ml) and the moderate to severe PC pneumonia group (46 +/- 4 micrograms/5 ml). There was a parallel reduction of diacylglycerol lipids: normal volunteers, 52 +/- 7 micrograms/5 ml; PC negative, 52 +/- 9 micrograms/5 ml; mild PC pneumonia, 35 +/- 7 micrograms/5 ml; and moderate to severe PC pneumonia, 15 +/- 2 micrograms/5 ml. Phospholipase A2 activity in moderate to severe PC pneumonia was twice that of the PC negative patients, and 30 times that for normals. The data demonstrate a marked diminution in surfactant glycerophospholipid in patients with AIDS and PC pneumonia and suggest a potential role for surfactant abnormality in the pathophysiology of this disease.

Adult↗
PubMed1991

Detection of interleukin 8 and tumor necrosis factor in normal humans after intravenous endotoxin: the effect of antiinflammatory agents.

Interleukin 8 (IL-8), a potent activator of neutrophils, may be important in the early host response to serious Gram-negative infections. IL-8 was measured with other acute phase cytokines (tumor necrosis factor alpha [TNF-alpha], IL-6 and IL-1 beta) in 25 normal humans randomized to receive either intravenous endotoxin alone or endotoxin after oral administration of ibuprofen or pentoxifylline, agents that alter some of the inflammatory responses induced by endotoxin in vitro. TNF immunoreactivity was maximum at 1.5 h, and total TNF (area under the curve) was 4.2- and 4.5-fold greater in subjects given endotoxin/ibuprofen compared to subjects given endotoxin alone (p = 0.026) or endotoxin/pentoxifylline (p = 0.004), respectively. IL-6 levels were maximum at 2-3 h and did not differ among the three groups. No IL-1 beta was detected in any subject. IL-8 levels peaked at 2 h in subjects given either endotoxin alone or endotoxin/pentoxifylline, falling towards baseline by 5 h. Subjects given endotoxin/ibuprofen had a more sustained rise in IL-8 with peak levels 2.8- and 2.5-fold higher at 3 h compared to endotoxin alone (p = 0.048) or endotoxin/pentoxifylline (p = 0.023), respectively. Differences in total IL-8 release among groups approached statistical significance (ANOVA, p = 0.07). This trend reflected the increased release of IL-8 by the subjects receiving ibuprofen compared to pentoxifylline (1.9-fold higher; p = 0.024). This suggests that cyclooxygenase products may provide important negative feedback loops for cytokine production in vivo. Increases in circulating IL-8 are part of the acute inflammatory response of humans to endotoxin. Altered cytokine responses caused by antiinflammatory therapy may have important implications for both host defense and injury during septicemia.

Adult↗
PubMed1991

Immunoglobulin G antineutrophil cytoplasmic antibodies are produced in the respiratory tract of patients with Wegener's granulomatosis.

Wegener's granulomatosis (WG) is a small-vessel vasculitis of unknown etiology that usually involves the upper and lower respiratory tract and the kidneys. Recently, an association has been made between the presence of serum antineutrophil cytoplasmic antibodies (ANCA) and WG. Because WG frequently involves the lung, we sought to evaluate bronchoalveolar lavage (BAL) fluids obtained from 14 patients with WG for the presence of ANCA. Immunoglobulin (Ig) G ANCA was found in the BAL with the same staining patterns as observed in the serum. Patients with active disease had the highest serum and BAL IgG ANCA titers. IgA or IgM ANCA was not detected in the serum or BAL of these patients. Protein analysis of BAL fluid revealed that patients with active, untreated WG had approximately a fourfold elevation in total protein (41.3 versus 10.5 mg/dl), with a disproportionately greater increase in the ratio of IgG to albumin (BAL IgG index = 1.49, normal = 0.74; p = 0.027). The increase of the IgG index in patients with active WG suggests that local production of IgG ANCA occurs in the lungs.

Adult↗
PubMed1991

Effect of aerosolized pentamidine prophylaxis on the diagnosis of Pneumocystis carinii pneumonia by induced sputum examination in patients infected with the human immunodeficiency virus.

This study assessed the effect of aerosolized pentamidine prophylaxis on the clinical presentation and diagnostic sensitivity of induced sputum examination for Pneumocystis carinii pneumonia. Between January 1, 1988 and October 27, 1990, 348 induced sputum examinations were performed as the initial diagnostic procedure for P. carinii pneumonia in patients infected with the human immunodeficiency virus (HIV). Medical records were reviewed for all induced sputum examinations, and the study group consisted of patients who either had not received prophylactic therapy (n = 193) or had received aerosolized pentamidine prophylaxis (n = 126). A total of 29 induced sputum examinations in patients receiving either other prophylactic regimens or ongoing therapy for previously documented P. carinii pneumonia were excluded from the study group. A total of 72 consecutive episodes of P. carinii pneumonia were subsequently documented by induced sputum examination (n = 54), bronchoalveolar lavage (n = 16), thoracocentesis (n = 1), or autopsy (n = 1). A total of 44 episodes occurred in patients who had not received antipneumocystis prophylaxis, and 28 episodes occurred in patients who had received aerosolized pentamidine. Of patients capable of producing a sputum specimen for analysis, induced sputum examination had a significantly lower diagnostic yield of 64.3% in patients who had received aerosolized pentamidine prophylaxis compared with 92.3% in patients who did not receive prophylaxis (p less than 0.02, Fisher's exact test). When the data were analyzed on an intention to treat basis, although there was a trend suggesting a lower overall yield in the aerosolized pentamidine patients, the difference was not statistically significant (64.3 versus 81.8%, p = 0.17, Fisher's exact test).(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗