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R C Bone

Publications and source records attributed to R C Bone.

At least 109 records · Page 6Linked to original sources
PubMed1991

The pathogenesis of sepsis.

Sepsis and its sequelae (sepsis syndrome and septic shock) are increasingly common and are still potentially lethal diagnoses. Many mediators of the pathogenesis of sepsis have recently been described. These include tumor necrosis factor alpha (TNF alpha), interleukins, platelet activating factor, leukotrienes, thromboxane A2, and activators of the complement cascade. Neutrophil and platelet activation may also play a role. Other agents that may participate in the sepsis cascade include adhesion molecules, kinins, thrombin, myocardial depressant substance, beta-endorphin, and heat shock proteins. Endothelium-derived relaxing factor and endothelin-1 are released from the endothelium and seem to exert a regulatory effect, counterbalancing each other. A central mediator of sepsis does not seem to exist, although TNF alpha has been commonly proposed for this role. Animal studies are difficult to extrapolate to the clinical setting because of cross-species differences and variations in experimental design. Rather than being caused by any single pathogenic mechanism, it is more likely that sepsis is related to the state of activation of the target cell, the nearby presence of other mediators, and the ability of the target cell to release other mediators. Also important is the downregulation or negative feedback of these mediators or the generation of natural inflammation inhibitors, such as interleukin-4 and interleukin-8. Endothelial damage in sepsis probably results from persistent and repetitive inflammatory insults. Eventually, these insults produce sufficient damage that downregulation can no longer occur; this leads to a state of metabolic anarchy in which the body can no longer control its own inflammatory response.

Animals↗
PubMed1991

An experiment in medical education. A critical analysis using traditional criteria.

In 1984, in addition to its standard traditional curriculum, Rush Medical College (Chicago, Ill) developed a Socratic problem-based method of teaching basic science material called the alternative curriculum. As part of an evaluation of this new curriculum, students in the two curricula were compared using three traditional measurements: (1) test scores from the National Board of Medical Examiners, Part I; (2) test scores from the National Board of Medical Examiners, Part II; and (3) performance on an oral examination. Alternative curriculum students did not differ significantly from their traditional curriculum classmates on National Board of Medical Examiners, Part I and Part II total scores, although their subset scores on Part I did tend to be lower, reaching significance in one subset area. Differences in performance favoring the traditional curriculum were primarily seen in the early years of the program. Alternative curriculum students in the class matriculated in 1987 scored significantly higher in three of five categories on the oral examination.

Adult↗
PubMed1991

The basis and basics of mechanical ventilation.

The development of mechanical ventilators and the procedures for their application began with the simple foot pump developed by Fell O'Dwyer in 1888. Ventilators have progressed through three generations, beginning with intermittent positive pressure breathing units such as the Bird and Bennett device in the 1960s. These were followed by second-generation units--represented by the Bennett MA-2 ventilator--in the 1970s, and the third-generation microprocessor-controlled units of today. During this evolutionary process clinicians recognized Types I and II respiratory failure as being indicators for mechanical ventilatory support. More recently investigators have expanded, clarified, and clinically applied the physiology of the work of breathing (described by Julius Comroe and other pioneers) to muscle fatigue, requiring ventilatory support. A ventilator classification system can help the clinician understand how ventilators function and under what conditions they may fail to operate as desired. Pressure-support ventilation is an example of how industry has responded to a clinical need--that is, to unload the work of breathing. All positive pressure ventilators generate tidal volumes by using power sources such as medical gas cylinders, air compressors, electrically driven turbines, or piston driven motors. Positive end-expiratory pressures, synchronized intermittent mandatory ventilation, pressure support ventilation, pressure release ventilation, and mandatory minute ventilation, are examples of the special functions available on modern ventilators. Modern third-generation ventilators use microprocessors to control operational functions and monitors. Because these units have incorporated the experience learned from earlier ventilators, it is imperative that clinicians understand basic ventilator operation and application in order to most effectively prescribe and assess their use.

Equipment Design↗
PubMed1991

Reduced alveolar macrophage production of tumor necrosis factor during sepsis in mice and men.

BACKGROUND AND METHODS: Tumor necrosis factor (TNF) has been implicated as a major humoral mediator of sepsis and endotoxin shock. TNF is secreted by cells of the reticuloendothelial system, including alveolar macrophages. Alveolar macrophage TNF production has been postulated to play a pathogenetic role in the development of adult respiratory distress syndrome (ARDS) in sepsis. To evaluate alveolar macrophage production of TNF during sepsis and endotoxin shock, we studied the effects of sepsis and/or in vivo lipopolysaccharide on the in vitro production of TNF by pulmonary alveolar macrophages. Human pulmonary alveolar macrophages were obtained by bronchoalveolar lavage from six septic and five nonseptic patients, cultured in the presence or absence of lipopolysaccharide (1 ng/mL), and assayed for TNF activity in a bioassay using fibroblast lysis. A murine model of sepsis was also utilized to study pulmonary alveolar macrophage TNF production under more controlled conditions. Normal mice were given ip injections of either lipopolysaccharide or saline. After 2 hrs, pulmonary alveolar macrophages were obtained and cultured in saline or various concentrations of lipopolysaccharide (0.001 to 10 micrograms/mL). RESULTS: There was no difference in baseline TNF activity, expressed as per cent lysis at 1:10 dilution, between pulmonary alveolar macrophages from control and septic patients (35.7 +/- 5.5% vs. 24.4 +/- 9.3%, respectively) (p greater than .05). However, when stimulated with lipopolysaccharide in vitro, the pulmonary alveolar macrophages from nonseptic patients produced significantly (p less than .01) more TNF (82.8 +/- 3.6%) than did pulmonary alveolar macrophages from patients with the septic syndrome (35.2 +/- 3.8%). Similar findings were obtained using the murine sepsis model. The baseline TNF activity in pulmonary alveolar macrophages from control mice was 22.9 +/- 7.0% (mean +/- SEM) and from lipopolysaccharide-injected mice was 26.8 +/- 3.3% (p greater than .05). Stimulation with 1 ng/mL lipopolysaccharide in vitro produced an increase in TNF activity in both groups, but the increase was greater in the control mice (68.1 +/- 5.7%) than in the lipopolysaccharide-injected mice (47.5 +/- 5.3%) (p less than .01). When the murine pulmonary alveolar macrophages were stimulated with higher concentrations of lipopolysaccharide (0.1 to 10 micrograms/mL), pulmonary alveolar macrophages from lipopolysaccharide-injected mice produced less than 25.5% of the TNF produced by pulmonary alveolar macrophages from control mice. CONCLUSIONS: These studies indicate that sepsis and endotoxin injection result in a rapid decrease in the ability of pulmonary alveolar macrophages from both humans and mice to produce and secrete TNF in response to lipopolysaccharide. We speculate that a downregulation of TNF production or of macrophage responsiveness to lipopolysaccharide has occurred. These results suggest that sustained TNF production by macrophages is not required for lung injury in sepsis.

Adult↗
PubMed1991

Gram-negative sepsis. Background, clinical features, and intervention.

Gram-negative sepsis remains an urgent medical problem, with more than 200,000 cases occurring each year in the United States and an associated mortality rate of 20 to 50 percent. Since the onset of shock greatly worsens prognosis and to encourage early intervention, the term sepsis syndrome was developed to describe the features of a preshock septic state. Early clinical and metabolic indicators are discussed, and current therapy is reviewed. Better understanding of the pathophysiology of endotoxin release from Gram-negative bacteria and advances in biotechnology have led to the development of potential new treatments for sepsis. One such development--monoclonal antibodies to endotoxin--has shown great promise in the effort to block the progression to septic shock, reduce mortality, and decrease the overall costs of sepsis to the patient and to the national economy.

Bacterial Infections↗
PubMed1991

The noninvasive respiratory care unit. Patterns of use and financial implications.

Clinical, socioeconomic, and ethical dilemmas have prompted reevaluation of traditional methods of providing intensive care. Six years ago, we established a noninvasive respiratory care unit (NRCU) for selected patients in need of intensive respiratory monitoring and therapy, particularly those requiring prolonged mechanical ventilation. One impetus for the formation of the NRCU was the expectation that it might prove to be a less costly alternative to the intensive care unit (ICU) for selected patients. We reviewed data from all patients admitted to the NRCU from July 1, 1987 through June 30, 1988 to identify characteristics of the patient population and to evaluate potential cost savings. During one year of operation, 136 patients were admitted to the unit, 107 of whom were mechanically ventilated. Overall, hospital costs for these patients exceeded payments by $1,519,477. Losses were greatest for mechanically ventilated patients and those for whom Medicare or Medicaid were the primary payors. Daily costs of care for mechanically ventilated patients were $1,976 lower in the NRCU than in the medical intensive care unit (MICU). We conclude that the NRCU represents a cost-effective approach to the care of substantial numbers of patients requiring specialized respiratory care.

Aged↗
PubMed1991

Sepsis syndrome. New insights into its pathogenesis and treatment.

Recent insights into the pathogenesis of sepsis and its sequelae have opened up new approaches to treatment. For maximum effectiveness, however, treatment must be given as early as possible in the course of illness--but only to patients who are at high risk of developing shock. The definition of sepsis syndrome outlined in this article provides a method by which to identify such patients before the onset of shock.

Animals↗
PubMed1991

Management of status asthmaticus.

Status asthmaticus is a medical emergency that requires careful evaluation and aggressive therapy. The mainstay of medical therapy is frequent administration of beta-agonist inhalations, combined with early corticosteroid use. Intravenous magnesium can be used as an adjunctive measure. If available, nebulized ipratropium bromide can be added to the regimen if side effects or poor response occurs to maximal dosages of beta-agonists. Nonconventional therapies should be considered only if conventional treatment fails. Signs and symptoms of deteriorating airflow and respiratory muscle fatigue should determine the need for mechanical ventilation. If mechanical ventilation is required, controlled hypoventilation may be best.

Humans↗
PubMed1990

Treatment of acute exacerbations in chronic obstructive pulmonary disease.

Therapeutic interventions introduced and refined over the last 10 years, including chronic home oxygen and improved bronchodilators, have resulted in more patients with chronic obstructive pulmonary disease living longer despite more severe functional abnormalities. Episodes of acute respiratory failure in this population remain a major complication requiring rapid assessment and intervention. This article focuses on the diagnostic approach and therapeutic interventions in the patient with obstructive lung disease who presents in acute respiratory distress.

Acute Disease↗
PubMed1990

Effects of prostaglandin E1 on oxygen delivery and consumption in patients with the adult respiratory distress syndrome. Results from the prostaglandin E1 multicenter trial. The Prostaglandin E1 Study Group.

We wanted to determine the long-term effects of a continuous infusion of PGE1 on DO2 and VO2 in patients with ARDS. Data were obtained from a randomized double-blind multicenter trial, which evaluated the effects of PGE1 on survival in patients with ARDS. Patients were stratified according to treatment and outcome: placebo-died (n = 8); PGE1-died (n = 12); placebo-survived (n = 9); and PGE1-survived (n = 8). In the placebo-died group, elevations occurred in VO2, which were associated with increases in O2ext and a constant DO2. In contrast, in the PGE1-died group, elevations in VO2 were associated with increases in DO2 and an unchanged O2ext. In the placebo-survived group, VO2 and DO2 decreased, whereas in the PGE1-survived group, VO2 and DO2 increased; however, O2ext decreased in both of these groups. Since impaired O2ext occurs in ARDS, PGE1-induced elevations in DO2, rather than compensatory increases in O2ext, may achieve better tissue oxygenation. We conclude that although the recently completed multicenter trial failed to show an enhancing effect of PGE1 on survival in patients with advanced ARDS, PGE1 may have important effects on oxygen transport and, therefore, may still have a role in the treatment of early manifestations of ARDS, either alone or in combination with other agents.

Alprostadil↗
PubMed1990

Dialysis-induced respiratory acidosis.

The inability to increase alveolar ventilation can lead to CO2 retention and acute respiratory acidosis in patients with ventilatory limitation. In this case, a young woman receiving maximum ventilatory support was unable to excrete excess CO2, associated with increasing dianeal concentrations of peritoneal dialysis. Since the patient's lung disease had necessitated a large amount of ventilatory support, the patient was unable to increase VE appropriately to handle excess CO2. Peritoneal dialysate was an additional source of carbohydrates. Peritoneal dialysate is an additional carbohydrate source that may result in hypercapnia and respiratory acidosis in patients with respiratory compromise. To our knowledge, this is the first case report in an adult which demonstrates that peritoneal dialysis with high glucose loads produced an acute respiratory acidosis that was reversed by decreasing the glucose concentrations in the dialysate. Excess CO2 production should be considered with respiratory disorders associated with dialysis.

Acidosis, Respiratory↗