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Biomedical subjects

S B Jones

Publications and source records attributed to S B Jones.

At least 19 recordsLinked to original sources

Otolaryngology in the information age: enabling technologies for the future of surgery. Enabling technologies for the future of surgery.

Enabling technologies for the future, whether exemplified by endoscopic, minimally invasive, or microdexterity systems or surgical and nonsurgical image-guided procedures, continue with an evolution so rapid that before one change has been accepted and perfected, another even more dramatic change promises to replace it. These information-based surgical and procedural interventions are just now becoming accepted standards of surgical, radiologic, and medical practice, and yet the promise of more advanced technologies blurs even these new boundaries, constantly redefining the concept of "surgery." It is essential that otolaryngologists, as part of the broader spectrum of physicians, understand these changes and prepare to adapt and improve each and every one of their technical and cognitive skills.

Computer Simulation

Laparoscopic surgery. Transition to the future.

The twenty-first century will usher in a fundamentally new approach to the practice of medicine. It will be based heavily on information technologies, broadly defined as the devices that acquire information; those that process, transmit, and distribute information; and those that use information to provide therapy. Although conventional surgery will continue to have a presence, there will be radically different surgical approaches and technologies that may become the predominant form of surgery. The medical record may become a three-dimensional visual representation of the individual patient (like the Visible Human Project), which can be the vehicle that integrates the entire spectrum of health care. Examples of the technologies and infrastructures that support this new approach to medicine are discussed and illustrated, with emphasis on how technologies improve individual patient care.

Forecasting

Effects of carbaryl, permethrin, 4-nonylphenol, and copper on muscarinic cholinergic receptors in brain of surrogate and listed fish species.

We investigated the regulation of the muscarinic cholinergic receptor (MChR) in brain from seven species of fish, two surrogates and five threatened or endangered species exposed to a series of chemicals as a measure of compensatory response among species. Fish were classified as either cold water (rainbow trout-surrogate, apache trout, lahanton trout) or warm water (fathead minnow-surrogate, razorback sucker, bonytail chub, colorado squawfish) and were exposed to chemicals shown to affect cholinergic pathways (carbaryl and permethrin) and two chemicals whose relationships to the cholinergic system is less clear (4-nonylphenol and copper). Downregulation of MChR occurred in all warm water species, except colorado squawfish, and at carbaryl concentrations similar to those causing downregulation observed in rainbow trout. Permethrin exposure resulted in downregulation in fathead minnow and razorback sucker, but the concentrations required for observation of this phenomenon were much greater than observed in cold water species. Copper exposure caused a decrease in brain MChR in rainbow trout and apache trout, whereas 4-nonylphenol exposure resulted in a decrease in brain MChR in all three cold water species. Our results indicate that surrogates are useful in assessing sublethal physiological responses to chemicals with a known mechanism of action such as carbaryl and support use of surrogates for assessing physiological responses to chemicals with diverse, less clear mechanisms of action.

Animals

Why not the best for the chronically ill?

Premium adjustors to neutralize risk selection among health plans are the weakest component in the technology for assuring competitive markets. It will be many years before we have adjustors adequate to free health plans to invest in and market improved managed care to predictably high-cost chronically ill persons. For want of a fair premium, health plans are driven by risk selection to underinvest in and otherwise "demarket" care to these very employees and beneficiaries whose costs and care most need to be managed. To achieve best value for the chronically ill, large employer coalitions, Medicare, and Medicaid should consider radical new approaches, such as establishing separate prices for care to people with specific chronic conditions and purchasing such care both from health plans and directly from provider systems.

Chronic Disease

Human immune cells mediate catecholamine secretion from adrenal chromaffin cells.

OBJECTIVES: To determine the ability of human mononuclear cells to produce factors that cause catecholamine secretion from adrenomedullary chromaffin cells; to determine conditions that stimulate mononuclear cells to produce such factors; and to compare these results with catecholamine secretion in response to the cytokines interleukin (IL)-1 and IL-2. DESIGN: Randomized, controlled, prospective study using in vitro conditions. SETTING: University research laboratory. SUBJECTS: Human mononuclear cells and porcine chromaffin cells. INTERVENTIONS: Circulating human mononuclear cells were isolated and cultured overnight in RPMI media. Cell-free media from these cultures (conditioned media) were then tested for the ability to cause epinephrine secretion from porcine chromaffin cells. Mononuclear cells were stimulated with phytohemagglutinin or by mixing cells from two different individuals while suppression was tested with dexamethasone. Catecholamine secretion in response to IL-1 and IL-2 (50 and 500 units/well, respectively), or nicotinic agonist dimethylphenylpiperazinium (10 microM, which mimics the action of acetylcholine), was tested for comparison. MEASUREMENTS AND MAIN RESULTS: Isolated porcine chromaffin cells had stable catecholamine content at the time of secretion measurements, and catecholamine release from cells into the media was measured using electrochemical detection after high-performance liquid chromatography separation. Catecholamine secretion was expressed as a percentage of the total cellular content. Epinephrine secretion due to human conditioned media was 6.9 +/- 1.0% compared with 1.4 +/- 0.6% for control media (p < .05) and 14.6 +/- 3.3% for dimethylphenylpiperazinium (p < .05). Epinephrine secretion with conditioned media from mixed cells (mixed leukocyte reaction) was 16.6 +/- 1.2%, which was higher than the epinephrine secretion caused by media from a single donor (6.9% +/- 1.0, p < .001). Pretreatment with dexamethasone inhibited the formation of bioactive products from mixed mononuclear cell preparations. Cytokines IL-1 and IL-2 did not stimulate chromaffin cell epinephrine secretion above background release with control media incubation. In all cases, norepinephrine secretion was similar to that of epinephrine, and results are included in all figures. CONCLUSIONS: Factors released from human immune cells can mediate epinephrine and norepinephrine release from adrenomedullary cells through a nonneural mechanism. Such immune cell factor release can be modulated by immunostimulation and steroid suppression. Release of such factors in vivo may contribute to increased circulating epinephrine in response to infectious challenge and may be an important factor in the critically ill patient.

Animals

Capitated risk-bearing managed care systems could improve end-of-life care.

Capitated or salaried managed care systems offer an important opportunity to provide high quality, cost-effective end-of-life care. However, capitated healthcare delivery systems have strong incentives to avoid patient populations in need of such care. Care currently provided at the end of life in fee-for-service practice is commonly deficient, with high rates of avoidable pain and other burdens. Only hospice offers a better track record, yet access to hospice is limited, and length of stay is short. Traditional staff- or group-model managed care plans, with their emphasis on prevention, patient education, cost efficiency, service coordination, and integrated provider networks, present a dynamic set of conditions and organizational structures that would support real change. Advantages derived from managed care systems providing quality end-of-life care include coordinated care across delivery sites, interdisciplinary teams, integrated services, and opportunities to develop innovative care programs, service arrays, utilization controls, and accountability for care standards. We propose a special comprehensive system of managed care, which we call MediCaring, for seriously ill persons nearing the end of life. MediCaring would encompass the best elements of palliative care within a managed care structure: comprehensive, supportive, community-based services that meet personal and medical needs, a focus on patient preferences, symptom management, family counseling, and support. Other programs, such as hospice, have shown that continuity and coordinated care, financed through a capitated payment and directed at a special population, are both feasible and effective. There are obstacles to improving care at the end of life. Managed care systems, like most of medical care, have largely ignored the terminally ill patient. Current financing arrangements make it financially undesirable for insurers to recruit or retain the very sick; very ill patients can be costly over a prolonged time. In addition, inertia and habit inhibit change, and there are few criteria by which to judge whether care at the end-of-life is "good." Nevertheless, capitated or salaried managed care systems committed to enhanced end-of-life care seem well positioned to achieve it if payment reimbursements were revised to encourage this end.

Aged

A strategy and demonstration for integrated biotechnology information.

Bioinformatics has developed as a key discipline to support science. Integrated access to the various new and established information resources is a key requirement for their future utility. A strategy for this integration has been developed and is being demonstrated to a core group of European users.

Biotechnology

Chromaffin cell epinephrine secretion mediated by a macrophage peptide: the role of endotoxin.

Recent studies show that mononuclear cells release a small peptide (molecular weight < 3,000) that stimulates chromaffin cell epinephrine secretion (1). The present study demonstrates that endotoxin (ETX) enhances this mononuclear cell-mediated epinephrine secretion and examines the potential mechanism for regulation of this peptide. Mononuclear cells from bovine spleen were cultured 24 h in serum-free media after which the supernatant (conditioned media, CM) was harvested and filtered to remove molecules with a molecular weight greater than 3,000. In vitro epinephrine secretion from bovine chromaffin cells was used as a test system and CM-secretion expressed as a percentage of total cell content. ETX challenge (1 microgram/mL) of mononuclear cell cultures significantly enhanced bioactivity of CM (control-CM = 11.8 +/- .7, ETX-CM = 17.7 +/- 2.8). Separation of cell populations by adherence to plastic revealed that T cell and/or B cell populations were the main source of the bioactive peptide(s) in unstimulated cell cultures (T/B cell = 12.9 +/- .7, M phi = 6.2 +/- .8). In contrast, ETX induced significant bioactive peptide release from the macrophage population (M phi = 6.2 +/- .8, ETX-M phi = 15.9 +/- 2.8). Polyacrylamide gel analysis revealed a small peptide in nonadherent cell CM that was present only in ETX-challenged macrophage cultures. Additionally, data are presented that demonstrate a correlation between CM bioactivity and protease activity in CM. Proteases secreted from mononuclear cells in response to ETX is hypothesized to cleave the bioactive peptide from a larger "parent" protein. This peptide may play a role in the elevation of plasma catecholamines observed in the setting of critical injury and illness and contribute to development of the systemic inflammatory response syndrome (SIRS) and subsequent shock states.

Animals

Resolution of abnormal MR signal intensity in patients with stress fractures of the femoral neck.

OBJECTIVE: The purpose of this study was to describe the natural evolution of abnormal MR signal intensity after the diagnosis of a stress fracture of the femoral neck and to ascertain the time to resolution of that abnormal signal intensity. SUBJECTS AND METHODS: Ten patients who had been previously diagnosed with stress fractures of the femoral neck after positive MR scans of the hip were examined with MR imaging at regular intervals. In each patient T1-weighted and short inversion time inversion recovery (STIR) sequences were obtained until the abnormally bright, diffuse MR signal intensity (representing edema) disappeared from the STIR images. Time to resolution was correlated with each patient's age and presence or absence of a fatigue line on MR imaging. Statistical analysis was done using Fisher's exact test. RESULTS: Edema resolved in seven patients within 3 months of initial diagnosis, in two patients within 6 months, and in the remaining patient within 12 months. We found no statistically significant correlation between time to resolution and patient age or the presence of a fatigue line on MR imaging. Residual sclerosis occurred in five patients, all of whom had a fatigue line. Two of these patients developed bright T1 signal (fatty marrow conversion) around the area of sclerosis. In the remaining three patients, STIR images revealed a brightened fatigue line, which we presumed was caused by granulation tissue. CONCLUSION: In this study, 90% of patients showed resolution of abnormal MR signal intensity on STIR imaging within 6 months of the initial diagnosis of stress fracture of the femoral neck. Such data may prove helpful in examining patients with recurrent symptoms who undergo repeated MR scanning. When an abnormally bright, diffuse MR signal intensity on STIR imaging is seen more than 6 months after an original injury, such abnormal signal intensity is likely to represent new injury.

Adult

Virtual reality surgical simulation and otolaryngology.

Large-scale flight simulation was pioneered in the 1940s to help meet the training requirements and demand for pilots in World War II. Flight simulators have been effective for training, evaluating, and certifying military and commercial pilots. Accurate scenarios have been developed that allow pilots in training to gain experience without the risk and expense of learning while in flight. The research in aviation simulation suggests a transfer effectiveness ratio of 0.48. This means that 1 hour in the simulator saves a half hour in the air. Because of the successful use of flight simulation as a training technique, computer-based simulators are now used in a variety of domains.

Computer Simulation

Evaluation of dithiol chelating agents as potential adjuvants for anti-IL-2 receptor lead or bismuth alpha radioimmunotherapy.

The dithiol chelating agents 2,3-dimercapto-1-propanesulfonic acid (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) were evaluated for use as potential adjuvants to reduce or prevent radiotoxicity in anti-interleukin-2 receptor (IL-2R) Lead-212 or Bismuth-212 alpha-radioimmunotherapy. DMPS was less toxic than DMSA to tumor cell lines in culture. No adverse effects on the ability of an anti-IL-2R monoclonal antibody (MAb) to bind to its specific antigen were detected using DMPS or DMSA at concentrations up to 600 ug/mL in 10% or 100% mouse serum. After a 5-day oral administration of chelating agent, neither acute nor chronic toxicities on blood hematology, blood chemistry or organ weights were observed for treated mice. DMPS and DMSA were effective in accelerating whole body clearance of the gamma-emitting tracer Bismuth-206. Both chelates significantly reduced femur uptake of tracer when compared to nontreated control mice. However, only DMPS prevented early (2 h postinjection) renal accumulation. These studies support the use of DMPS as a potential adjuvant chelation therapy in Lead-212 or Bismuth-212 radioimmunotherapy protocols.

Adjuvants, Immunologic

What is driving health system change?

Socially amoral economic forces now drive health system change. The authors, assisted by a panel of experts on employers, health plans, providers, and consumers, discuss current drivers such as (1) employers' price-focused purchasing, without good quality/value measures; (2) health plans' growing successes and market clout; (3) providers declining prospects and fears about their future; and (4) consumers' worries about less choice. Future influences will include Medicare reforms, better information, and pro-consumer regulation of managed care, as well as rising social distress. The health system's future is now open for resolution in an evolving, imperfect market.

Choice Behavior

5,7-dihydro-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-6H- pyrrolo[3,2-f]-1,2-benzisoxazol-6-one: a potent and centrally-selective inhibitor of acetylcholinesterase with an improved margin of safety.

A series of N-benzylpiperidines (2a-d, 10) with novel isoxazole-containing tricycles has been prepared. This series has shown potent in vitro inhibition of the enzyme acetylcholinesterase (AChE), with IC50S = 0.33 - 3.6 nM. Compound 2a was the most potent inhibitor with an IC50 = 0.33 +/- 0.09 nM. Derivatives 2a-d and 10 displayed weak in vitro inhibition of butyrylcholinesterase (BuChE) with IC50S = 600 - 23,000 nM. The most selective compound was 2a with a BuChE/AChE ratio in excess of 4 orders of magnitude (> 10,000). Pyrrolobenzisoxazole 2a also displayed a favorable profile in vivo. In microdialysis experiments, 2a produced a 200% increase in extracellular levels of acetylcholine (ACh) at a dose of 0.4 mg/kg in freely moving, conscious rats. Peripheral side effects (salivation ED50 = 26 +/- 1.5 mg/kg) and acute lethality (LD50[1 h] = 42 mg/kg) were observed at > 60-fold higher doses. These data indicate that 2a is an AChE inhibitor with good central selectivity and a favorable margin of safety. Compound 2a, designated as CP-118,954, is currently in clinical development for the treatment of cognitive disorders.

Animals