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Biomedical subjects

A F Suffredini

Publications and source records attributed to A F Suffredini.

At least 55 records · Page 3Linked to original sources
PubMed1991

Ocular permeability after systemic administration of endotoxin in humans.

Acute anterior uveitis in response to the administration of systemic gram-negative endotoxin was studied in humans. The blood-aqueous barrier was evaluated in eight normal human subjects at 8 or 24 hours after systemic administration of purified gram-negative endotoxin. No significant changes in the blood-aqueous barrier were found, as evaluated by permeability to fluorescein, number of aqueous cells, flare, or intraocular pressure, despite profound endotoxin-induced cardiac, pulmonary, and circulatory effects. Gram-negative endotoxin does not appear to affect the human blood-aqueous barrier in doses that can safely be given to humans.

Adult↗
PubMed1990

Septic shock in humans. Advances in the understanding of pathogenesis, cardiovascular dysfunction, and therapy.

Septic shock is the commonest cause of death in intensive care units. Although sepsis usually produces a low systemic vascular resistance and elevated cardiac output, strong evidence (decreased ejection fraction and reduced response to fluid administration) suggests that the ventricular myocardium is depressed and the ventricle dilated. In survivors, these abnormalities are reversible. Failure to develop ventricular dilatation in nonsurvivors suggests that dilatation is a compensatory mechanism needed to maintain adequate cardiac output. With a canine model of septic shock that is very similar to human sepsis, myocardial depression was confirmed using load-independent measures of ventricular performance. Endotoxin administration to humans simulates the qualitative, cardiovascular abnormalities of sepsis. The pathogenesis of septic shock is extraordinarily complex. Diverse microorganisms can generate toxins, stimulating release of potent mediators that act on vasculature and myocardium. A circulating myocardial depressant substance has been closely associated with the myocardial depression of human septic shock. Therapy has emphasized early use of antibiotics, critical care monitoring, aggressive volume resuscitation, and, if shock continues, use of inotropic agents and vasopressors. Pharmacologic or immunologic antagonism of endotoxin or other mediators may prove to enhance survival in this highly lethal syndrome.

Animals↗
PubMed1990

Serum neopterin levels following intravenous endotoxin administration to normal humans.

Endotoxin was administered intravenously to five normal subjects. Measurement of serum neopterin levels demonstrated no significant change from baseline during the first 6 h after endotoxin administration, but were elevated two to four-fold at 24 h. In the three subjects in whom it was measured, a two-fold rise of the mean serum neopterin levels persisted at 48 h. The acute inflammatory events initiated by endotoxin administration to normal humans result in a delayed, but sustained, rise in serum neopterin levels which persists well after the acute phase response has subsided.

Acute-Phase Reaction↗
PubMed1990

Atypical pathologic manifestations of Pneumocystis carinii pneumonia in the acquired immune deficiency syndrome. Review of 123 lung biopsies from 76 patients with emphasis on cysts, vascular invasion, vasculitis, and granulomas.

The frequency of atypical pathologic manifestations of Pneumocystis carinii pneumonia (PCP) were studied in 123 lung biopsy specimens from 76 National Institutes of Health patients with the acquired immune deficiency syndrome. The following atypical features were observed: interstitial (63%) and intraluminal (36%) fibrosis, absence of alveolar exudate (19%), numerous alveolar macrophages (9%), granulomatous inflammation (5%), hyaline membranes (4%), marked interstitial pneumonitis (3%), parenchymal cavities (2%), interstitial microcalcification (2%), minimal histologic reaction (2%), and vascular invasion with vasculitis (1%). These atypical features are discussed with emphasis on the significance of cavities, vascular invasion, vasculitis, and granulomas. Immunohistochemical staining with monoclonal antibodies to the 2G2 and 6B8 antigens of P carinii in paraffin-embedded lung biopsy specimens did not indicate any diagnostic advantage over routine methenamine silver stains. This study provides an important reminder that a wide variety of pathologic manifestations may occur in PCP in human immunodeficiency virus-infected patients and that atypical features should be sought in lung biopsies from patients at risk for PCP.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Detection of renal blood flow abnormalities in septic and critically ill patients using a newly designed indwelling thermodilution renal vein catheter.

To evaluate alterations in renal blood flow in sepsis-induced renal failure, we developed and studied a percutaneously placed thermodilution renal blood flow catheter in eight critically ill patients. Para-aminohippurate extraction coefficients were decreased, supporting the need for renal vein sampling to determine CPAH in sepsis. Thermodilution and CPAH methods correlated strongly, confirming the reliability of this thermodilution method. Renal vascular resistance, an indicator of renal vascular function, remained unchanged throughout the bouts of sepsis. The fraction of total body arterial blood flow going to the kidneys rose significantly during recovery from sepsis. Glomerular filtration rate, which was reduced in four of seven septic patients, correlated with the fraction of total blood flow going to the kidneys. These results suggest that renal vascular abnormalities may be occurring during septic shock. Our study demonstrates that sepsis-induced renal dysfunction may occur despite normal ranges of total renal blood flow during shock.

Acute Kidney Injury↗
PubMed1989

A prospective, randomized, controlled trial of prednisone for dilated cardiomyopathy.

Although prednisone has been used to treat patients with idiopathic dilated cardiomyopathy, its efficacy has not been rigorously studied. We therefore randomly assigned 102 patients to either treatment with prednisone (60 mg per day) or a control group. At three months, improvement, defined prospectively as an increase in the ejection fraction of greater than or equal to 5 percentage points, was observed in 53 percent of the patients receiving prednisone and 27 percent of the controls (P = 0.005). The mean (+/- SE) ejection fraction increased 4.3 +/- 1.5 percentage points (from 17.9 +/- 1.0 to 22.2 +/- 1.6 percent) in the prednisone group, as compared with 2.1 +/- 0.8 percentage points (from 17.1 +/- 1.1 to 19.3 +/- 1.4 percent) in the control group (P = 0.054). All patients were categorized prospectively in two separately randomized subgroups. "Reactive" patients (n = 60) were those who had fibroblastic (n = 36) or lymphocytic (n = 2) infiltration or immunoglobulin deposition (n = 16) on endomyocardial biopsy, a positive gallium scan (n = 7), or an elevated erythrocyte sedimentation rate (n = 18). "Nonreactive" patients (n = 42) had none of these features. At three months, 67 percent of the reactive patients who received prednisone had improvement, as compared with 28 percent of the reactive controls (P = 0.004). Nonreactive patients did not improve significantly with prednisone (P = 0.51). After three months, reactive patients who received prednisone daily were switched to alternate-day therapy (60 mg every other day), and after six months the improvement seen earlier was no longer present. These data suggest that patients with idiopathic dilated cardiomyopathy may have some improvement when given a high dose of prednisone daily. However, the increases in the ejection fraction that we observed during prednisone treatment were small, their duration was limited, and the side effects were important. Overall, prednisone was judged to have only marginal clinical benefit, and should not be administered as standard therapy for dilated cardiomyopathy.

Cardiomyopathy, Dilated↗
PubMed1989

The cardiovascular response of normal humans to the administration of endotoxin.

Marked abnormalities in cardiovascular function accompany septic shock, and bacterial endotoxin is believed to be one of the principal mediators of these abnormalities. To evaluate the cardiovascular effects of endotoxemia in humans, we measured hemodynamic variables in nine normal subjects given an intravenous bolus dose of endotoxin (Escherichia coli, 4 ng per kilogram of body weight) and in six normal subjects given a bolus dose of saline, before and three hours after administration. All the subjects then underwent volume loading with normal saline (mean, 2217 ml) during the fourth and fifth hours after administration of the bolus, and the measurements were repeated. Three hours after the administration of endotoxin and before volume loading, the cardiac index had increased by 53 percent and the heart rate by 36 percent (both changes were significant; P less than or equal to 0.008), and the systemic vascular-resistance index had decreased by 46 percent (P = 0.004). After volume loading (five hours after the administration of endotoxin), the left ventricular ejection fraction decreased by 1 percent of the base-line value in the subjects given endotoxin, but increased by 14 percent in the controls (P = 0.008). The left ventricular end-diastolic and end-systolic volume indexes increased by 18 percent (P = 0.07) and 24 percent (P = 0.042), respectively. Left ventricular performance, as measured by the ratio of the peak systolic pressure to the end-systolic volume index, was depressed (a decrease of 0.90 in the subjects given endotoxin vs. an increase of 0.76 in the controls; P = 0.024). We conclude that the administration of endotoxin to normal subjects causes a depression of left ventricular function that is independent of changes in left ventricular volume or vascular resistance. The changes in function are similar to those observed in septic shock and suggest that endotoxin is a major mediator of the cardiovascular dysfunction in this condition.

Adult↗
PubMed1989

CD4 counts as predictors of opportunistic pneumonias in human immunodeficiency virus (HIV) infection.

STUDY OBJECTIVE: To determine if circulating CD4+ lymphocyte counts are predictive of specific infectious or neoplastic processes causing pulmonary dysfunction. DESIGN: Retrospective, consecutive sample study. SETTING: Referral-based clinic and wards. PATIENTS: We studied 100 patients infected with human immunodeficiency virus (HIV) who had had 119 episodes of pulmonary dysfunction within 60 days after CD4 lymphocyte determinations. MEASUREMENTS AND MAIN RESULTS: Circulating CD4 counts were less than 0.200 X 10(9) cells/L (200 cells/mm3) before 46 of 49 episodes of pneumocystis pneumonia, 8 of 8 episodes of cytomegalovirus pneumonia, and 7 of 7 episodes and 19 of 21 episodes of infection with Cryptococcus neoformans and Mycobacterium avium-intracellulare, respectively. In contrast, circulating CD4 counts before episodes of nonspecific interstitial pneumonia were quite variable: Of 41 episodes, 11 occurred when CD4 counts were greater than 0.200 X 10(9) cells/L. The percent of circulating lymphocytes that were CD4+ had a predictive value equal to that of CD4 counts. Serum p24 antigen levels had no predictive value. CONCLUSIONS: Pneumocystis pneumonia, cytomegalovirus pneumonia, and pulmonary infection caused by C. neoformans or M. avium-intracellulare are unlikely to occur in HIV-infected patients who have had a CD4 count above 0.200 to 0.250 X 10(9) cells/L (200 to 250 cells/mm3) or a CD4 percent above 20% to 25% in the 60 days before pulmonary evaluation. Patients infected with HIV who have a CD4 count below 0.200 X 10(9) cells/L (or less than 20% CD4 cells) are especially likely to benefit from antipneumocystis prophylaxis.

Cryptococcosis↗
PubMed1989

Promotion and subsequent inhibition of plasminogen activation after administration of intravenous endotoxin to normal subjects.

To evaluate the effect of endotoxin on the fibrinolytic response, we administered Escherichia coli endotoxin (4 ng per kilogram of body weight) intravenously to 19 healthy volunteers and measured fibrinolytic proteins, protease inhibitors, neutrophil elastase, and von Willebrand factor in serial blood samples obtained over 24 hours. One hour after endotoxin administration, the level of tissue plasminogen activator (t-PA) antigen rose from 10 to 23 ng per milliliter, peaking at 52 ng per milliliter at three hours. The level of alpha 2-plasmin inhibitor-plasmin complexes increased sevenfold, peaking at three hours. Plasminogen-activator inhibitor-1 activity rose more slowly, from 7 U per milliliter to a maximum of 49 U per milliliter at five hours. The concentrations of neutrophil elastase and von Willebrand antigen were unchanged at one hour, increased approximately threefold by 3 hours, and remained elevated at 24 hours. None of these measures changed in a control group (n = 5) given intravenous saline instead of endotoxin. We studied t-PA functional activity in four subjects. The level of activity rose rapidly, from 1.2 ng per milliliter at base line to 8.3 ng per milliliter at one hour and 13.9 ng per milliliter at two hours; it was undetectable at three hours. This increase in plasminogen activator activity was abolished in vitro by incubation of t-PA with an antiserum specific for human t-PA, suggesting that t-PA may be directly responsible for plasmin generation in the response to endotoxin. We conclude from this study of healthy subjects that endotoxin activates the fibrinolytic system, beginning with release of t-PA in the blood within one hour. The early activation of plasmin by endotoxin may prevent thrombosis, and the increase in fibrinolysis is then offset by the release of plasminogen activator inhibitor.

Adult↗
PubMed1988

Nonspecific interstitial pneumonitis without evidence of Pneumocystis carinii in asymptomatic patients infected with human immunodeficiency virus (HIV).

STUDY OBJECTIVE: To assess how often Pneumocystis carinii organisms, P. carinii pneumonia, or other pulmonary pathologic processes were present in persons infected with human immunodeficiency virus (HIV) without pulmonary symptoms or previous history of P. carinii, and with a normal chest roentgenogram. DESIGN: Serial, prospective assessment of eligible HIV-seropositive patients over 21 months. PATIENTS: Twenty-four HIV-seropositive patients with either a nonpulmonary manifestation of the acquired immunodeficiency syndrome (AIDS) (n = 12) or an absolute CD4 lymphocyte count of 0.200 X 10(9) cells/L or less (n = 12), no pulmonary symptoms, a normal chest roentgenogram, no history of P. carinii pneumonia, and no history of treatment with antipneumocystis prophylaxis. INTERVENTIONS: Pulmonary assessment with arterial blood gases, pulmonary function tests, gallium-67 citrate scans, and bronchoscopy with bronchoalveolar lavage and transbronchial biopsies. MEASUREMENTS AND MAIN RESULTS: Mean alveolar-arterial gradient was 11.1 mm Hg +/- 8.5 and mean diffusion capacity was 73.0% +/- 20.0% of predicted. None of the 24 patients showed P. carinii or other pathogens on stains of bronchoalveolar lavage fluid. No patient had histologic evidence of P. carinii pneumonia. Transbronchial biopsy specimens showed chronic, nonspecific interstitial pneumonitis (11 of 23) and no pathologic abnormality (12 of 23). Six patients have developed P. carinii pneumonia during 2 to 18 months of follow-up. CONCLUSIONS: HIV-infected patients without pulmonary symptoms did not have detectable Pneumocystis organisms in bronchoalveolar lavage fluid or transbronchial biopsy specimens; but 11 of 23 had evidence of chronic, nonspecific interstitial pneumonitis. Pneumocystis organisms in a pulmonary specimen from a symptomatic patient probably indicate the cause of the pulmonary dysfunction even if only a few are detected.

Adult↗
PubMed1987

Prognostic factors and life expectancy of patients with acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia.

To assess determinants of prognosis for 43 patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia, objective clinical and histopathologic characteristics were analyzed for acute and long-term prognostic significance. Severe abnormalities on initial chest radiographs and alveolar-arterial oxygen differences (AaPO2) greater than 30 mm Hg were associated with higher mortality during the period of treatment for the acute episode (p less than 0.05). Decreased long-term survival after the diagnosis of Pneumocystis pneumonia correlated with the severity of interstitial edema (a component of diffuse alveolar damage) on initial transbronchial biopsy and elevation of AaPO2 at the time of diagnosis (Cox proportional hazards analysis, p less than 0.05). The persistence of Pneumocystis cysts after 3 wk of therapy was associated with significantly decreased long-term survival (p less than 0.05) when follow-up biopsy was performed in 27 of the patients. Patients with a diagnosis of Pneumocystis pneumonia before July 1985 had more advanced disease at the time of diagnosis and a worse prognosis than did those in whom the diagnosis was made after July 1985 (p less than 0.05). This study demonstrates that important prognostic information can be derived from information obtained at initial presentation and follow-up bronchoscopic evaluation in patients with AIDS and Pneumocystis carinii pneumonia, and suggests that early detection and initiation of therapy may improve chances for survival.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Nonspecific interstitial pneumonitis in patients with AIDS: radiologic features.

Chest radiographic abnormalities in patients with AIDS usually are associated with opportunistic infection or neoplasm. One hundred five patients with AIDS and clinical evidence of pneumonitis had chest radiographs and underwent bronchoscopy with bronchoalveolar lavage, transbronchial biopsy, or open-lung biopsy. Chest radiographs were abnormal in 73 (70%). Pneumocystis carinii pneumonia was identified at bronchoscopy or open-lung biopsy in 52 (50%). Nonspecific interstitial pneumonitis occurring in the absence of an identifiable infection was documented histologically in 36 (34%). Twenty (56%) of these 36 patients had abnormal chest radiographs. No currently recognized infectious agents were recovered from lavage fluid or were seen histopathologically in patients with nonspecific interstitial pneumonitis. The results show that nonspecific interstitial pneumonitis is clinically and radiologically indistinguishable from Pneumocystis carinii pneumonitis and should be considered in the differential diagnosis of AIDS patients with interstitial infiltrates.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Nonspecific interstitial pneumonitis: a common cause of pulmonary disease in the acquired immunodeficiency syndrome.

During a 4.4-year period, nonspecific interstitial pneumonitis was seen in 41 of 110 (38%) patients with the acquired immunodeficiency syndrome and accounted for 32% (48/152) of all episodes of clinical pneumonitis. Diffuse alveolar damage was typically a feature of nonspecific interstitial pneumonitis, but neither lung biopsy nor bronchoalveolar lavage detected a pathogen. Of these 41 patients, 13 had no associated pulmonary tumor and had not been exposed to pulmonary toxins, whereas 28 patients had either concurrent pulmonary Kaposi sarcoma, previous experimental therapies, or a history of pneumocystis pneumonia or drug abuse. Of these 41, 23 had normal chest radiographs. The clinical features of patients with nonspecific interstitial pneumonitis were similar to those of patients with pneumocystis pneumonia, although histologic findings showed less severe alveolar damage in patients with nonspecific interstitial pneumonitis (p less than 0.001). Pathologic evaluation and clinical follow-up suggest that many clinical episodes of pneumonitis in patients with the acquired immunodeficiency syndrome are due to nonspecific interstitial pneumonitis of unknown cause.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Long-term prognosis of survivors of Pneumocystis carinii pneumonia. Structural and functional correlates.

Limited data exist detailing the long-term sequelae of Pneumocystis pneumonia. Open lung biopsies were obtained in seven renal transplant recipients within 48 hours of the onset of respiratory failure. Biopsy specimens and simultaneous chest roentgenograms were graded without clinical information according to the severity of alveolar damage and pulmonary infiltrates, respectively. Evaluation of pulmonary function and exercise physiology were performed 15 to 21 months after their illness. Pulmonary function indices were normal except FRC (2.65 +/- 0.56 L or 77 +/- 16 percent of predicted) and Dsb (20.0 +/- 7.2 ml/min/mm Hg or 79 +/- 19 percent of predicted). Two patients developed arterial desaturation with exercise. Alveolar damage scores correlated with later exercise arterial desaturation (r = 0.88, p less than 0.05). Simultaneous roentgenographic scores correlated with later abnormalities of Dsb (r = 0.81, p less than 0.05). Mild residual abnormalities of pulmonary function were found in five of seven adult survivors of Pneumocystis pneumonia. These abnormalities correlated with pathologic and radiographic features of the acute illness.

Adult↗
PubMed1985

Acute respiratory failure due to Pneumocystis carinii pneumonia: clinical, radiographic, and pathologic course.

The clinical, radiographic, and pathologic correlates of acute respiratory failure due to Pneumocystis carinii pneumonia were studied in 12 renal transplant patients treated with cyclosporin (CS) and prednisone. Six patients required only supplemental oxygen, while the other six patients developed the adult respiratory distress syndrome (ARDS) requiring prolonged mechanical ventilation despite similar predisposing factors and prompt initiation of therapy. Ten (83%) patients survived. Increased frequency of human leukocyte antigen (HLA) DR6 was noted in six of the 11 patients tested. The resolution of radiographic infiltrates was significantly slower in ARDS patients; however, there was no apparent difference in the severity of early alveolar damage between the two groups. There was also no association between the development of ARDS due to P. carinii pneumonia and the mean daily dose of CS and prednisone, the presence of cytomegalovirus infection or pneumonia, HLA-DR6 antigen, or initial hypoxemia.

Acute Disease↗
PubMed1984

Pneumocystis carinii pneumonia in renal-transplant recipients treated with cyclosporine and steroids.

Fourteen of 156 renal-transplant recipients treated with cyclosporine and steroids developed Pneumocystis carinii-related pneumonia (PCP) over a 19-month period. This was a significant change from past experience with this disease in renal-transplant patients receiving azathioprine and steroids (six cases among 179 patients from 1977 to 1981). Epidemiological investigation failed to implicate either person-to-person or nosocomial spread of infection. Cases of PCP occurred more frequently in males. Twelve patients (86%) had onset of disease in the third or fourth months after transplantation. Comparison of cases to matched controls revealed that the cases had received lower doses of steroids and had a higher incidence of cytomegalovirus infection. This suggested that the cases may have been more effectively immunosuppressed than the controls. After institution of prophylaxis with trimethoprim-sulfamethoxazole, no further cases of PCP developed.

Adolescent↗