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Biomedical subjects

B A Fisher

Publications and source records attributed to B A Fisher.

At least 19 recordsLinked to original sources

Dietary fatty acid modulation of mucosally-induced tolerogenic immune responses.

Immunological unresponsiveness or hyporesponsiveness (tolerance) can be induced by feeding protein antigens to naive animals. Using a classical oral ovalbumin gut-induced tolerance protocol in BALB/c mice we investigated the effects of dietary n-6 and n-3 polyunsaturated fatty acids (PUFA) on high-and low-dose oral tolerance (and in non-tolerised animals, i.e. effects of antigen challenge alone) in relation to lymphoproliferative, cytokine and antibody responses. Fish oil rich in long-chain n-3 fatty acids decreased both T-helper (Th) 1- and Th2-like responses. In contrast, borage (Borago officinalis) oil rich in n-6 PUFA, of which gamma-linolenic acid is rapidly metabolised to longer-chain n-6 PUFA, increased Thl-like responses and decreased Th2-like responses, and possibly enhanced suppressor cell or Th3-like activity. These findings are in general agreement with other studies on the effects of long chain n-3 PUFA on immune system functions, and characterise important differences between long-chain n-3 and n-6 PUFA, defining more precisely and broadly the immunological regulatory mechanisms involved. They are also discussed in relation to autoimmune disease.

Animals↗

Future of the emergency physician: subject or citizen?

Seventy-seven percent of emergency physicians (EPs) work as either employees or independent contractors (ICs). In contrast, other hospital-based physicians such as radiologists and anesthesiologists have a much higher percentage of ownership in their medical practices. The development of a high percentage of nonownership arrangements among EPs finds a useful historical comparison in the industrialization of nonhealth care workers over the past 100 years. Unless significant changes occur in emergency medicine (EM) organization and practice structures, EPs will have less self-determination over their practice compared with other specialties. This will inevitably result in less self-determination for their future. Combined with the great strides EM has achieved as a specialty, EPs' brightest future lies in being citizens of a broader, more expansive, all encompassing EM practice.

Contract Services↗

Mucosal challenge of Macaca nemestrina with simian immunodeficiency virus (SIV) following SIV nucleocapsid mutant DNA vaccination.

A simian immunodeficiency virus (SIV)(Mne) DNA clone was constructed that produces viruses containing a four amino acid deletion in the second zinc finger of the nucleocapsid (NC) domain of the Gag polyprotein. Viruses produced from this clone, although non-infectious both in vitro and in vivo, complete a majority of the steps in a single retroviral infection cycle. Eight pig-tailed macaques (Macaca nemestrina) were inoculated intramuscularly and subcutaneously three times over the course of 24 weeks with the NC mutant expressing DNA. These macaques, and four controls, were then challenged mucosally (intrarectally) with the homologous virus (SIV Mne CL E11S) and monitored for evidence of infection and clinical disease. Prior to challenge, a measurable humoral immune response was noted in four of eight immunized macaques. After challenge, all 12 macaques became infected, although four immunized animals greatly restricted their viral replication, and one immunized animal that controlled replication remains antibody negative. No disease has been evidence during the 46-week period of monitoring after challenge.

Animals↗

Protection of Macaca nemestrina from disease following pathogenic simian immunodeficiency virus (SIV) challenge: utilization of SIV nucleocapsid mutant DNA vaccines with and without an SIV protein boost.

Molecular clones were constructed that express nucleocapsid (NC) deletion mutant simian immunodeficiency viruses (SIVs) that are replication defective but capable of completing virtually all of the steps of a single viral infection cycle. These steps include production of particles that are viral RNA deficient yet contain a full complement of processed viral proteins. The mutant particles are ultrastructurally indistinguishable from wild-type virus. Similar to a live attenuated vaccine, this approach should allow immunological presentation of a full range of viral epitopes, without the safety risks of replicating virus. A total of 11 Macaca nemestrina macaques were inoculated with NC mutant SIV expressing DNA, intramuscularly (i.m.) in one study and i.m. and subcutaneously in another study. Six control animals received vector DNA lacking SIV sequences. Only modest and inconsistent humoral responses and no cellular immune responses were observed prior to challenge. Following intravenous challenge with 20 animal infectious doses of the pathogenic SIV(Mne) in a long-term study, all control animals became infected and three of four animals developed progressive SIV disease leading to death. All 11 NC mutant SIV DNA-immunized animals became infected following challenge but typically showed decreased initial peak plasma SIV RNA levels compared to those of control animals (P = 0.0007). In the long-term study, most of the immunized animals had low or undetectable postacute levels of plasma SIV RNA, and no CD4(+) T-cell depletion or clinical evidence of progressive disease, over more than 2 years of observation. Although a subset of immunized and control animals were boosted with SIV(Mne) proteins, no apparent protective benefit was observed. Immunization of macaques with DNA that codes for replication-defective but structurally complete virions appears to protect from or at least delay the onset of AIDS after infection with a pathogenic immunodeficiency virus. With further optimization, this may be a promising approach for vaccine development.

Animals↗

What the role of the modern ED should be.

Managed care organizations (MCOs) have recently focused on the high cost per patient visit in the Emergency Department (ED). MCOs emphasize preventing low acuity patients access to the ED, believing that billions of healthcare dollars will be saved. However, a review of emergency department studies suggests a different outcome. Combined with new ED service lines, perhaps another, rather paradoxical approach to managing healthcare costs in the ED is more patient focused and more cost-effective long-term. This approach is more comprehensive and offers more services, not less. The ED is an important community resource and entry port to healthcare. It is the only place open 24-hours per day, 7 days per week with no appointment necessary, and all lab and radiology services available. The very claim that it is "overutilized" is an indication of its success. In large volume EDs, certain patient populations may be more specifically served with pediatric emergency, industrial medicine, and fast track physicians. Special facilities for chest pain patients or observation can treat patients more quickly, keep them out of hospital beds, thus lowering costs. In smaller hospitals, the well rounded ED physician can treat patients of all acuities. In the most rural communities the ED can become the local 24-hour clinic with short-term stay beds. EDs are fixed costs to hospitals. Extracting low acuity patients from the ED will raise costs for emergency patients and leave the facility underutilized. By appropriately raising prices for emergencies and decreasing low acuity patient charges to reflect marginal expense, the ED becomes a cost friendly environment for the low acuity patient.

Acute Disease↗

The emergency department under managed care: exploring an alternative model.

An obvious emphasis by managed care organizations is to limit emergency department care to only the most emergent patients. The result? A "lean & mean" department. However, another approach would be to encourage emergency department care--it offers more comprehensive services to both the managed care organization and the patient. And this professional paper explains how it's possible.

California↗

Effects of DMSO, pH, stretch and calcium on the thick filaments in an amphibian smooth muscle.

Conventional fixation with glutaraldehyde fixatives at pH 7.4 did not preserve/promote thick filaments in Bufo smooth muscle. However, if pH was lowered to 6.0, thick filaments were present and addition of dimethyl sulfoxide (DMSO) led to a greater number of thick filaments. Stretch alone had little effect on the presence of thiber seen. Calcium had little effect on the numbers of thick filaments, but it affected the appearance of the thick filaments. Low calcium (10(-7) M) caused a higher proportion of rod-shaped filaments, while in high calcium (10(-3) M) most thick filaments were ribbons. The great lability of the thick filaments in amphibian smooth muscles makes them ideal for studying factors which affect the appearance of thick filaments in smooth muscle, but it also raises the question of the degree of aggregation of myosin in the living cell.

Animals↗

Reorientation of myofilaments during contraction of a vertebrate smooth muscle.

The purpose of the investigation was to determine whether filaments within smooth muscle cells changed their orientation (with respect to the main axis of the cell) during contraction. The stomach muscle of Bufo marinus was used, since its cells may be easily isolated, enabling direct observation in living cells. In addition to still micrography, cinemicrography was used to record continuously during contraction. Polarization microscopy revealed a change in birefringence after contraction, with relaxed cells exhibiting uniform birefringence while contracted cells displayed a discontinuous pattern. Movies revealed a progressive change in orientation of birefringent elements from nearly parallel to the cell's main axis in relaxed cells to increasingly larger angles to the cell's axis as contraction progressed. Phase-contrast microscopy revealed a change in filamentous components, from being parallel to the cell's axis in relaxed cells to being in an undulating or helical pattern during concentration. Cell shape tended to follow the configuration of the filamentous component. Electron microscopy of muscle strips corroborated the observations of living cells and substantiated the conclusion that filaments change their orientation from parallel to oblique (with respect to the cell's axis) during shortening with an undulating or helical pattern of filaments in shortened muscles.

Animals↗

Serf or citizen: physician status and organizational structure.

For more than a decade, dynamic changes in the health care industry have created new organizations for physicians. The major change for physicians has not been the organization itself, but the principles by which it is governed. This fundamental shift is studied with its impact on physicians, by analogy, becoming more like serfs or more like citizens. A review of the general organizational direction and results of non-physician health care organizations is made followed by the statistical trends of physician groups. Historical comparisons of non-health care industries are made with current organizational choices of physicians and physician groups. Observations of physician decisions are made identifying the direction they send physician status along the continuum from serf to citizen. Physicians are unknowingly making decisions regarding the principles by which they will be governed in new organizations. The choices they are making give them less autonomy and less opportunity to make future choices. The seductive invitation to spend less time in administrative matters and more time practicing medicine is a siren's call that will diminish the status of physicians and the autonomy by which medicine is practiced.

Collective Bargaining↗

Enhancing the medical practice: consorting with the emergency department.

In 1994, the Department of Emergency Medicine at Loma Linda University Medical Center (LLUMC) set out to implement a comprehensive emergency department (ED) model: a model that headed in the opposite direction of popularized solutions of which the objective is to keep patients out of the ED. This model increases the number of services offered. It triages patients within its walls to an area cost effective for the patient's acuity and allows patients to immediately move to a higher level of care if the provider sees the need. Three years of data have determined the comprehensive ED model to be an effective, patient-focused alternative to the "demand management" methods. Low-acuity patients at LLUMC are treated in less costly areas. The high-tech-laden "MainED" is better utilized because of a 25% increase in complex patients since 1993. In addition, the comprehensive ED model appears to be a valuable resource that enhances the outpatient medical practice.

Comprehensive Health Care↗