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Biomedical subjects

E Brown

Publications and source records attributed to E Brown.

At least 109 records · Page 6Linked to original sources

The ultimate goal? It depends.

The knowledge that cervical cancer should be a preventable disease has provided the impetus to improve the Pap smear. Now, for the first time in 50 years, two new computerized technologies are available--the AutoPap and Papnet systems--that could change the way they are interpreted. Of course, these new innovations come at a price, perhaps doubling or tripling the cost--by one estimate, the new technologies could add $1 billion per year. The health policy issue is whether these innovations address the limitations of cervical cancer screening programs in an efficient way. The analysis is entirely different when cast as an individual patient care issue. Here the patient and physician, who serves as her advocate, want to use the best screening method. The goal is not how to best allocate resources to improve the health of the overall population, but instead how to get the best care for the individual patient.

Cost-Benefit Analysis↗

Halfway technologies.

An extraordinary gamut of medical and surgical therapies could be considered "halfway technologies," addressing mere symptoms or manifestations of disease, rather than the underlying pathogenesis. When a "halfway" technology is also lifesaving, its value cannot be underestimated by the individual patient. The example of organ transplantation explored in this column represents a halfway technology. It does not treat the underlying disease itself, but reflects the absolute failure of all efforts at medical and conservative therapy and is a last ditch, gerry-rigged lifesaving solution. And what about "quarter technologies"--the bridge to transplant devices--designed to get the patient halfway to the final halfway procedure?

Health Knowledge, Attitudes, Practice↗

Preventing malnutrition in patients on CAPD.

Malnutrition is not uncommon in patients on CAPD. Thorough assessment and accurate records are essential for recognition of early indicators. Dietary advice can improve compliance. Intraperitoneal infusion of amino acids may be useful in some patients.

Humans↗

Panel discussion: impact of guidelines on third-party payors and HMOs.

Utilization management (preauthorization) has given way to disease management, i.e., the management, by providers in cooperation with third-party payors, of patients and their disease states from beginning to end. Managed-care organizations are seeking guidelines-based cancer disease management programs that result in: lower, more predictable costs; authoritative quality assurance; measured outcomes; reduced preauthorization disputes; and improved management of cases in clinical trials. Guidelines also need to provide some consistency and consensus regarding the management of common clinical problems. Good guidelines help assist managed-care companies gather data, build a more solid utilization management foundation and support a clinically sound disease management program. Aetna's Institutes of Excellence (IOE) program seeks to address the issue of coverage for high-dose chemotherapy and bone marrow transplantation, but can serve as a useful model for the development of comprehensive cancer networks.

Clinical Trials as Topic↗

Prevention of acute graft-versus-host disease by treatment with a novel immunosuppressant. Cholera toxin B subunit.

Transplantation of allogeneic bone marrow (BM) is often complicated by the development of acute graft-vs-host disease (GVHD) caused by contaminating T cells in BM inocula because of activation of the host reactive T effector cells. Using a murine model for acute GVHD caused by injection of parental C57Bl/6 splenocytes into unirradiated (C57Bl/6 x DBA/2) F1 hybrids, we demonstrated that pretreatment of the inocula with a novel immunosuppressant, B subunit of cholera toxin (CT-B) impaired the ability of C57Bl/6 T cells to induce acute GVHD in F1 recipients. F1 mice injected with CT-B-treated C57Bl/6 splenocytes did not develop significant splenomegaly, and no antihost CTLs were found in their spleens. Moreover, these mice did not suffer from aplastic anemia, nor from general immunosuppression. Immunofluorescence studies suggest that treatment of the inducing inocula with CT-B selectively prevents accumulation of the host-reactive CD8+ T cells in F1 mice. Furthermore, our experiments demonstrated that CT-B treatment does not impair the ability of BM progenitors to form colonies in semisolid culture or in lethally irradiated hosts. Thus, taken together, our data suggest that ex vivo CT-B treatment can be used in allogeneic BM transplantation to prevent acute GVHD.

Animals↗

Improved viability of hepatic allografts from fasted donors is associated with decreased peripheral TNF activity.

Despite improvements in preservation solutions, hepatic allografts continue to be lost from primary nonfunction. Previous work by this group and others has established that donor fasting improves the viability of hepatic allografts. We have also established an association between viability of stored organs and serum TNF levels. The purpose of this study was to determine whether improved viability of hepatic allografts from fasted donors is associated with lower peripheral serum TNF levels. TNF was measured using a bioassay employing a WEHI cell line. Transplanted livers from fasted donors displayed gross deglycogenation had less bile flow postrevascularization and increased postoperative AST, but had significant improvement in viability and were associated with significantly less TNF recovered from the peripheral circulation. The association of improved viability and diminished serum TNF and previous work that links changes in postrevascularization TNF levels with changes in Kupffer cell activity suggest a possible cause for improved survival of recipients of fasted allografts.

Animals↗

Inactivation of Kupffer cells after prolonged donor fasting improves viability of transplanted hepatic allografts.

Data from recent studies suggest that donor fasting imparts a beneficial effect on the viability of transplanted hepatic allografts. Because starvation may temporarily inactivate Kupffer cells, and because these cells are the likely mediators of liver injury after prolonged preservation-reperfusion, the purpose of this study is to establish a link between improved organ viability and Kupffer cell inactivation caused by donor allograft fasting. In an in vivo rat liver transplant model, 48 hours of donor fasting (1) improved allograft viability, (2) significantly decreased Kupffer cell phagocytosis, and (3) significantly decreased cytokine (tumor necrosis factor [TNF]) production postrevascularization. These data validate work from previous studies demonstrating that donor fasting improves allograft viability and furthermore support our previous research implicating activation of Kupffer cells as a causative agent of cold ischemia-preservation injury.

Animals↗

Outcome of polymicrobial peritonitis in continuous ambulatory peritoneal dialysis patients.

Polymicrobial peritonitis is a relatively uncommon, but potentially serious complication that develops in continuous ambulatory peritoneal dialysis (CAPD) patients. Its cause and optimal management remain controversial. The authors reviewed the frequency and natural history of polymicrobial peritonitis in 432 CAPD patients. Of 1,405 episodes of peritonitis, 80 were polymicrobial (6%). Patients with polymicrobial peritonitis were similar to all CAPD patients in age, gender, race, and underlying renal disease. Diabetes mellitus, human immunodeficiency virus (HIV) status, and clinically apparent gastrointestinal disease did not predisposes patients to polymicrobial peritonitis. Thirty days after the polymicrobial peritonitis, 64 patients remained on CAPD (80%), and at 180 days 48 patients continued CAPD. Prior exit-site infections were present in 12 patients (14%) with polymicrobial peritonitis. Only 22% of patients required catheter removal to treat the infection. We conclude that polymicrobial peritonitis accounts for 6% of the total episodes of peritonitis; diabetes, HIV infection, and underlying gastrointestinal disease are not more prevalent in patients with multiorganism infections. Most patients continue CAPD therapy at 30 and 180 days after the episode of polymicrobial peritonitis.

AIDS-Associated Nephropathy↗

Delivery of glucocorticoids by jet nebulization: aerosol characteristics and output.

BACKGROUND: Since inflammation has been identified as a critical factor in the pathogenesis of asthma, use of inhaled glucocorticoids has increased. Because young children are often unable to coordinate properly the use of metered-dose inhalers and no glucocorticoids preparations for nebulization have been approved in the United States, parenteral and intranasal glucocorticoids preparations are occasionally administered by nebulization. METHODS: We examined whether a parenteral preparation (triamcinolone acetonide [TAA]; Kenalog) could be delivered by nebulization. TAA, 1000 micrograms (0.1 ml), was placed in the nebulizer bowl (MB5 [MeFar, Brescia, Italy] or Pari-Jet [Dura Pharmaceuticals, San Diego, Calif.]), then diluted with 2.9 ml normal saline solution for a total volume fill of 3 ml. Using a laser particle analyzer, high-performance liquid chromatography, and cascade impactor, we examined the percentage of aerosol volume produced with particles in the respirable range of 1 to 5 microns in diameter, actual TAA output (in micrograms) and concentration of TAA contained in the particles within the respirable range. RESULTS: Laser particle analysis indicated that 34% +/- 3% (mean +/- SEM) (MB5) and 47 +/- 3% (Pari-Jet) of the total aerosol volume produced were within the respirable range of 1 to 5 microns in diameter, and this remained consistent throughout nebulization. The nebulizer was stopped serially for determination of TAA output with high-performance liquid chromatography. TAA output (1000 micrograms less the amount in micrograms remaining after nebulization) was essentially complete after 2 minutes with the Pari-Jet and within 4 minutes with the MB5 and totaled 352 +/- 19 micrograms and 367 +/- 9 micrograms, respectively. Finally, cascade impactor studies confirmed that 33.4% of the TAA aerosol generated by the MB5 nebulizer was contained in particles in the respirable range. CONCLUSION: Approximately 35% (Pari-Jet) and 37% (MB5) of the initial 1000 micrograms of TAA was delivered with the two nebulizers tested. The particles generated within the respirable range were limited to 34% (MB5) and 47% (Pari-Jet) of the amount delivered. TAA was equally distributed in the particles generated. The theoretic amount delivered in the respirable range was approximately 12.5% for the MB5 nebulizer on the basis of the cascade impactor and 16.5% for the Pari-Jet (assuming TAA distribution equivalence) of the TAA placed in each of the nebulizers. Additional clinical studies are needed to define efficacy and safety in view of the excipients used in preparing the parenteral preparation.

Aerosols↗

Tuberculosis among urban health care workers: a study using restriction fragment length polymorphism typing.

Cases of tuberculosis identified during 1992-1994 through an active tuberculosis surveillance network among six hospitals that serve New York City (the TBNetwork) were analyzed according to the occupational status of the patients. Clinical data were obtained by review of medical records, and restriction fragment length polymorphism (RFLP) typing of Mycobacterium tuberculosis isolates was performed. No known nosocomial outbreaks of tuberculosis occurred at these hospitals in the study period. Occupational status was known for 142 of 201 patients whose isolates were available for strain typing. Patients infected by organisms with a clustered strain typing pattern, as determined by RFLP analysis, were presumed to have recently acquired disease. RFLP typing revealed that isolates from 13 (65%) of 20 health care workers and 50 (41%) of 122 non-health care workers had a clustered RFLP pattern. The strains infecting eight (89%) of nine health care workers seropositive for human immunodeficiency virus (HIV) had a clustered RFLP pattern. Multivariate analysis of 75 patients with known HIV and occupational status revealed that HIV status (P = .03) and health care worker status (P = .02; RR = 2.77) were independent risk factors for a clustered RFLP strain. These findings suggest that many of the apparently sporadic cases of tuberculosis among health care workers may be due to unrecognized occupational transmission.

Adult↗

Transmission of Toxoplasma gondii in Panama City, Panama: a five-year prospective cohort study of children, cats, rodents, birds, and soil.

A cohort of more than 500 children from Panama City, Panama was studied prospectively over five years for acquisition of antibody to Toxoplasma gondii. The direct agglutination test showed that 72 of 571 children seroconverted between one and six years of age, for a cumulative incidence of 12.6%. Children were examined by pediatricians quarterly, and illnesses that had occurred in the interval and their activities were noted on questionnaires. Thirty-eight variables were examined for their role as risk factors for seroconversion. There was a higher correlation between children's seroconversion and contact with dogs than with cats. Combinations of significant predictors without dogs explained only 67% of the seroconversions, but the same factors with dogs explained 90%. On the other hand, ingestion of raw or rare meat or eggs appeared to play no role in transmission. Cats were examined and 110 (45.6%) of 241 had Toxoplasma antibody on the first bleeding. Only two (0.5%) of 383 cat fecal specimens, when tested in mice, resulted in seroconversion. Ten (1.1%) of 924 soil samples resulted in seroconversion in mice that had been injected. Antibody to Toxoplasma was found in 52 (23.3%) of 226 rats (Rattus norvegicus) and two (0.035%) of 571 mice (Mus musculus). Two hundred sixteen birds of 16 different species were bled. Antibody to Toxoplasma was found in 13.4% of these birds, mostly in grackles, blue-gray tanagers, and doves. The rate of isolation of Toxoplasma was low: one of 23 in rats and three of 201 in birds. High relative risks (RRs) of transmission to children were predicted by contact histories with nursing dogs (RR = 5.8), weaned dogs (RR = 4.7), many flies (RR = 3.6), 6-12-month-old dogs (RR = 3.4), weaned cats (RR = 3.0), 6-12-month-old cats (RR = 2.7), nursing cats (RR = 2.5), much garbage (RR = 2.4), and many roaches (RR = 2.2). The high statistical correlation of dog contact with seroconversion in children suggests the possibility that dogs, by eating and rolling in cat feces, are instrumental in mechanically transmitting Toxoplasma infection. In addition, flies, and to a lesser extent, cockroaches, may have practically important roles in transmission.

Animals↗