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Biomedical subjects

A M Fein

Publications and source records attributed to A M Fein.

At least 37 records · Page 2Linked to original sources
PubMed1996

Delayed resolution of pneumonia. When is slow healing too slow?

Slowly resolving or nonresolving pneumonia is a clinical challenge, but we believe it can be dealt with in a rational and decisive manner. The following risk factors have been established for delayed radiographic resolution of pneumonia and should be considered in patient evaluation: Coexisting medical conditions History of smoking, Advanced age, Multilobar involvement, Persistent fever or leukocytosis. Diabetes, chronic obstructive pulmonary disease, renal failure, and alcohol abuse can impair immune function, which slows normal clearing of infiltrates. Common and uncommon infectious agents, conditions that mimic pneumonia (eg, a neoplasm, congestive heart failure), and pulmonary complications (eg, abscess) can also result in delayed resolution.

Humans↗
PubMed1995

A second large controlled clinical study of E5, a monoclonal antibody to endotoxin: results of a prospective, multicenter, randomized, controlled trial. The E5 Sepsis Study Group.

OBJECTIVE: To evaluate the safety and efficacy of E5, a murine, monoclonal antibody directed against endotoxin, in the treatment of patients with Gram-negative sepsis. DESIGN: A multicenter, randomized, double-blind, placebo-controlled trial. SETTING: Fifty-three hospitals across the United States, including university medical centers, Veterans Affairs Medical Centers, and community hospitals. PATIENTS: 847 patients were randomized into this study. Enrolled patients met criteria for three conditions: a) known or suspected Gram-negative infection; b) clinical evidence of sepsis; and c) signs of end-organ dysfunction. Patients with refractory shock were excluded from the study. INTERVENTIONS: Two doses of E5 (2 mg/kg/day by intravenous infusion 24 hrs apart), or placebo that was identical in appearance were administered. In addition, all patients received standard supportive therapy and broad-spectrum antibiotics. MEASUREMENTS AND MAIN RESULTS: The primary end point was mortality over 30 days. Secondary outcome measures included the resolution and prevention of organ failure in the same two populations. Additionally, the safety of E5 was evaluated. There was no significant improvement in survival over 30 days among patients with Gram-negative sepsis who received E5 compared with those patients who received placebo (n = 530; p = .21). In addition, E5 did not improve survival for patients with Gram-negative sepsis and organ failure (n = 139; p = .3). However, a significantly greater percentage of patients with Gram-negative sepsis experienced resolution of major organ failure if they received E5, compared with those patients who received placebo (n = 139; 48% E5 vs. 25% placebo; p = .005). This result extended to all patients who entered the study with one or more major organ failures, regardless of the etiology of the infection (n = 225; 41% E5 vs. 27% placebo; p = .024). E5 also provided protection against the development of some organ failures, but significant prevention was only observed for adult respiratory distress syndrome (p = .007) and central nervous system dysfunction (p = .050). Hypersensitivity reactions attributable to E5 occurred in 2.6% of patients. An asymptomatic antibody response occurred in 44% of the E5-treated patients and in 12% of the patients who received placebo. CONCLUSIONS: In this study, E5 did not reduce mortality in nonshock patients with Gram-negative sepsis whether or not those patients also had organ failure. However, E5 did result in greater resolution of organ failure in patients with Gram-negative sepsis. This benefit extended to those patients with suspected Gram-negative etiology. This finding is important because patients with suspected Gram-negative sepsis and organ failure can be identified without waiting for culture results. In addition, E5 resulted in the prevention of adult respiratory distress syndrome and central nervous system organ failure. However, more studies are needed to determine if this result can be extended to organ failure in general. E5 is safe as a treatment for patients with Gram-negative sepsis.

Antibodies, Monoclonal↗
PubMed1995

Cytokines affect pseudomonas binding to tracheal cells via a neutrophil-mediated process.

Critical illness is often associated with gram-negative bacterial colonization of the airways, increasing the risk of nosocomial pneumonia. Cytokines, released in response to endotoxin, might contribute to this phenomenon by causing changes in epithelial cell binding of bacteria. To investigate this possibility, human monocytes and hamster pulmonary macrophages were cultured without or with Escherichia coli endotoxin (10 micrograms/ml) for 4 and 24 h. Hamster and human tracheal epithelial cells were treated with supernates from monocyte cultures for 24 h, and subsequent binding of 14C-labeled Pseudomonas aeruginosa to the epithelial cells was measured (percent adherence). In separate experiments, recombinant human (rh) tumor necrosis factor-alpha (TNF-alpha) (25 to 100 ng/ml) and interleukin-1 beta (IL-1 beta) (2,000 to 8,000 pg/ml) were added to hamster monolayers. Neither monocyte supernates nor purified cytokines were toxic to the epithelial cells for up to 48 h. There was no significant change in P. aeruginosa adherence to either hamster or human tracheal epithelial cells after 24 h of exposure to culture supernates from either endotoxin-stimulated human monocytes or hamster macrophages. Similarly, purified rhTNF and rhIL-1 exposure did not increase bacterial adherence. However, when polymorphonuclear leukocytes were coincubated with the monocyte supernates and epithelial cells, P. aeruginosa adherence was significantly increased. Moreover, this effect was enhanced by an epithelial cell-derived substance. Thus, while inflammatory cytokines may participate in enhancing bacterial colonization of the lung in vivo, they do not do so by a direct action on tracheal epithelial cells but can act via a neutrophil-dependent mechanism.

Animals↗
PubMed1994

Pneumonia in the elderly. Special diagnostic and therapeutic considerations.

Clinical and radiologic signs and symptoms of gram-negative infections are often muted or obscured by a concurrent disease, and therefore, are not reliable for predicting the infecting organisms. Thus, initial therapy is nearly always empiric and based on the clinician's judgment that a patient's pneumonia is likely to be caused by particular pathogens. The choice of an appropriate regimen requires careful consideration of the extent and severity of coexisting illness and debilitation, the severity of the pneumonia, and the level of care required.

Aged↗
PubMed1994

Critical care medicine in managed competition and a managed care environment.

The high cost of medical care in the United States and diminishing access to health care for many Americans has spurred healthcare reform efforts in this country. Several bills have been introduced into Congress. Many of these healthcare bills and other proposals embrace the concept of managed care and managed competition as their central feature. The steady growth of managed care organizations and the possible adoption of managed competition stands to significantly alter the way critical care medicine is practiced and delivered in the United States. The number of ICUs and ICU beds may be reduced, affecting both patient case mix and the overall mission of the ICU and critical care practice. Furthermore, fewer critical care practitioners may be available as a result of diminished educational funding and reduced training programs. In view of these and other impending changes in the American healthcare system, it is vital to investigate the impact of managed care on ICU practice and patient outcome and to study the incremental and value-added contributions of critical care medicine.

Cost Control↗
PubMed1994

Severe pneumonia in the elderly.

The elderly are more susceptible to pneumonia and more likely to die from this infection than younger populations. Older patients with pneumonia requiring hospitalization are more likely to develop complications necessitating longer hospital stays. This article focuses on features of common lower respiratory tract infections and physiologic and immunologic characteristics of elderly patients that might obscure classic clinical presentation of pneumonia. Treatment factors unique to elderly patients with severe pneumonia are also discussed.

Age Factors↗
PubMed1993

Cost-effectiveness of monoclonal antibodies to gram-negative endotoxin in the treatment of gram-negative sepsis in ICU patients.

OBJECTIVE: To evaluate the fiscal impact and the cost-effectiveness of monoclonal antibodies against gram-negative endotoxin (MAbGNE) in the treatment of presumed gram-negative sepsis. DESIGN: A decision analysis model was developed from (1) data from two phase III trials that studied the E5 or HA-1A MAbGNE, and (2) financial data from 1405 septic patients who required intensive care at a large tertiary hospital. SETTING: Intensive care unit (ICU) patients with presumed gram-negative sepsis. PATIENTS: The E5 trial evaluated 468 patients, and the HA-1A study enrolled 543 patients with presumed gram-negative sepsis. INTERVENTIONS: The addition of MAbGNE to standard regimens or standard regimens alone. MAIN OUTCOME MEASURES: Total expected charges and the expected probability of survival were determined for each option. Cost-effectiveness and marginal cost-effectiveness ratios were also derived. Multiple sensitivity and Monte Carlo analyses were performed to test the underlying assumptions. RESULTS: MAbGNE therapy always resulted in higher expected charges; however, these differences were less than its acquisition cost by $870. The cost-effectiveness ratio for MAbGNE, for $2000 and $4000 acquisition costs, was $71,674 and $74,900 per probability of survival, respectively. Sensitivity analysis showed that cost-effectiveness was most affected by diagnostic accuracy, patient selection, and acquisition cost. Monte Carlo analysis showed that MAbGNE was more costly for 71% of simulations, yet the most efficacious option for 79% of simulations. CONCLUSIONS: From the perspective of acute care institutions, MAbGNE is expensive and cannot be justified on a cost-saving basis. However, it may be cost-effective throughout a reasonable range of assumptions.

Antibodies, Monoclonal↗
PubMed1993

The economic impact and cost-effectiveness of monoclonal antibody therapy for sepsis.

Monoclonal antibodies directed against the endotoxins produced by gram-negative organisms have been developed for the treatment of patients with sepsis. Phase 3 clinical trials in which two of these agents, E5 and HA-1A, have been evaluated have suggested possible benefit in terms of improved survival and reversal of organ dysfunction for certain subgroups. Since monoclonal antibodies are expected to be expensive, cost-effectiveness analysis is necessary to assess the joint clinical and economic impact. Cost-effectiveness studies based on the clinical data from these phase 3 trials have suggested that monoclonal antibodies may represent a cost-effective approach to the treatment of sepsis. However, an increase in the number of questions concerning the clinical efficacy of these agents and their ultimate impact on survival mandates the need for further clinical and economic investigation.

Antibodies, Monoclonal↗
PubMed1993

Nonresolving and slowly resolving pneumonia. Diagnosis and management in the elderly patient.

Pneumonia is both more prevalent in the elderly and more severe. This article reviews the approach to nonresolving or slowly resolving pneumonia in the elderly. Specific attention will be given to the natural history of commonly occurring pneumonias in this age group, related host defense impairments, unusual infectious causes of slowly resolving pneumonia, and noninfectious mimics of pneumonia.

Aged↗
PubMed1993

The approach to nonresolving pneumonia in the elderly.

Evaluation of slowly resolving or nonresolving pneumonia in the elderly must be based on clear evidence that the disease is behaving outside of the expected norms. Several weeks may be required for even a "typical" pneumonia to resolve in the elderly with comorbid illness. In the presence of an underlying host impairment, the patient should be observed for several additional weeks unless clinical clues raise the suspicion of an unusual infection or noninfectious process. If there is no further evidence of improvement over the extended period of observation, further evaluation is indicated, looking for an unusual infection (particularly tuberculosis or fungal disease) or a noninfectious diagnosis (particularly neoplasm). In our experience, fiberoptic bronchoscopy and computerized tomography are extremely useful first steps in the evaluation of nonresolving pneumonias after an appropriate period of observation.

Aged↗
PubMed1992

Nonresolving pneumonia in steroid-treated patients with obstructive lung disease.

PURPOSE: To review autopsy-proven cases of opportunistic pneumonia and determine how many of these patients had received corticosteroid therapy for obstructive lung disease in order to define whether this therapy was the major risk factor predisposing to infection. PATIENTS AND METHODS: All autopsies performed at Winthrop-University Hospital over a 5-year period were reviewed, and 30 cases of opportunistic pneumonia were identified. In eight of 30 cases, corticosteroid therapy for chronic obstructive pulmonary disease (COPD) was the only identifiable risk factor for opportunistic infection. The other 22 patients had other well-defined risk factors for infection. Chart review of the eight patients with COPD was undertaken to define the clinical features of their infections. RESULTS: All eight patients had a progressive multilobar pneumonia that failed to resolve, either clinically or radiographically, despite the use of multiple broad-spectrum antibiotics. In four cases, the infection was community-acquired, while in the other four cases, it was nosocomial in origin. Despite the presence of a nonresolving pneumonia, opportunistic infection was generally not considered as a diagnostic possibility, with only one case being correctly diagnosed antemortem. Autopsy examination documented Aspergillus species as being responsible for six episodes of pneumonia, Candida albicans accounting for one episode, and cytomegalovirus accounting for one episode. CONCLUSION: Based on this experience, it is clear that corticosteroid therapy of COPD can lead to opportunistic pulmonary infection, in or out of the hospital. This diagnosis should be considered when patients receiving this therapy develop a pneumonia that fails to respond to broad-spectrum antibiotics.

Aged↗
PubMed1992

Sleep in normal late pregnancy.

Twelve women in their third trimester of pregnancy and 10 age-matched nonpregnant controls underwent complete polysomnography for one night in the laboratory. Seven of the original women returned for a second study 3-5 months postpartum. During late pregnancy, women showed increased wake after sleep onset (WASO) and a lower sleep efficiency in comparison with the control group. The percentage of rapid eye movement (REM) sleep was significantly decreased and the percentage of stage 1 significantly increased compared to the nonpregnant group. At 3-5 months postpartum, a significant reduction in WASO and increased sleep efficiency were noted. However, only a slight increase was noted in REM sleep during the postpartum period compared to the prepartum period. The most frequent sleep complaints in the pregnant group were restless sleep, low back pain, leg cramps and frightening dreams. In summary, in accordance with their complaints, women in their third trimester demonstrated polysomnographic patterns of sleep maintenance insomnia.

Adult↗