Biomedical subjects

R V Maier

Publications and source records attributed to R V Maier.

At least 109 records · Page 6Linked to original sources

PubMed1992

Ketoconazole inhibits alveolar macrophage production of inflammatory mediators involved in acute lung injury (adult respiratory distress syndrome).

BACKGROUND: Acute inflammatory lung injury (adult respiratory distress syndrome [ARDS]) causes significant morbidity and death in surgical patients. The alveolar macrophage elaborates proinflammatory mediators implicated in acute pulmonary injury. The macrophage products, leukotriene B4 (LTB4), thromboxane A2 (TXA2), and procoagulant activity (PCA), initiate inflammatory cascades that lead to microvascular thrombosis and neutrophil infiltration, two common features of ARDS. One potential method of preventing or attenuating lung injury is to inhibit the production of inflammatory mediators. Preliminary studies indicate that ketoconazole, known primarily for its antifungal properties, may prevent ARDS. METHODS: LTB4, TXB2, and PCA production by rabbit alveolar macrophages was measured after treatment with endotoxin or Ca ionophore and ketoconazole or selective 5-lipoxygenase (MK 886) and thromboxane synthetase (imidazole) inhibitors. RESULTS: Ketoconazole significantly inhibits alveolar macrophage production of LTB4, TXB2, and PCA. Ketoconazole inhibition of PCA is independent of effects on 5-lipoxygenase and thromboxane synthetase. CONCLUSIONS: Ketoconazole inhibition of alveolar macrophage proinflammatory mediators may be of benefit in preventing ARDS by minimizing neutrophil infiltration and microvascular thrombosis. Inhibition of 5-lipoxygenase and thromboxane synthetase, without affecting cyclooxygenase, may offer a selective advantage by allowing production of other homeostatic eicosanoids.

Animals↗

PubMed1992

To be or not to be?

Explore the source record for details and available documents.

Costs and Cost Analysis↗

PubMed1991

Why surgeons prefer not to care for trauma patients.

A survey of the Washington State Chapter of the American College of Surgeons was undertaken to document the opinions of surgeons on trauma care issues. Thirty-nine percent of the total sample of surgeons who responded would prefer not to treat any trauma patients. These surgeons were more likely to be older, to practice in an urban setting, to feel that trauma call has a negative impact on elective practice, and to believe more strongly that reimbursement from trauma patients is not equal to that of nontrauma patients. They also agreed more strongly with the statements that these patients require a greater time commitment and pose an increased medicolegal risk. The most significant influence on preference not to treat trauma patients was exerted by the perception of a negative impact on practice, older age, and perception of increased medicolegal risk. Reimbursement issues and location of practice were less influential factors. This information can be used to target concerns and barriers to active, willing participation in a trauma care system and to tailor strategies to deal with them effectively.

Adult↗

PubMed1991

Interferon gamma increases sensitivity to endotoxin.

Interferon-gamma (IFN-gamma) has been proposed for use following severe trauma to reverse depressed macrophage (M phi) function and thereby reduce infection, sepsis, and subsequent multiple organ failure syndrome (MOFS). However, an excessive inflammatory response by M phi s and other components of the inflammatory cascade is thought to be central to the underlying pathophysiology of MOFS. Endotoxin (LPS) has been implicated as a principal mediator of sepsis-induced MOFS by stimulating M phi s and leukocytes (WBC). This study addresses the following question: Does IFN-gamma predispose normal rabbits to a pathophysiologic response to LPS infusion? Four groups of New Zealand White rabbits (n = 6, each group) were prepared for measurement of cardiac output, arterial pressure, arterial PO2, and WBC counts over a 6-hr period. Group I (control) was instrumented alone, Group II (LPS alone) was given a subclinical dose of 1.0 micrograms/kg of Escherichia coli LPS iv, Group III (IFN-gamma alone) was given recombinant rabbit IFN-gamma (5.0 micrograms/kg subcutaneous) for 3 days prior to preparation for measurements, and Group IV (IFN-gamma + LPS) received 3 days of IFN-gamma followed by LPS. One hour prior to sacrifice 5.0 microCi of 125I-albumin was given and bronchoalveolar lavage was performed at death to determine the lavage/plasma 125I ratio as an index of pulmonary permeability. The results indicate that IFN + LPS animals had significant decreases in cardiac output, PO2, and WBC counts, and increased lavage/plasma ratio of 125I-albumin when compared to all other groups (P less than 0.05 by ANOVA, t test). Neither LPS alone nor IFN-gamma alone had a significant effect on measured variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Flexion distraction and chance injuries to the thoracolumbar spine.

Seat belt legislation has resulted in increased restraint use by passengers in automobiles in Washington State. At Harborview Medical Center in Seattle, we have observed an increased incidence of seat belt-related injuries. Twenty cases of Chance-type thoracolumbar flexion-distraction fractures were reviewed retrospectively. Thirteen patients (65%) had associated life-threatening intra-abdominal trauma. Twelve of these patients had bowel wall injury. Ninety percent of the children had combined abdominal and spinal injury. Operative treatment of the spinal injury resulted in correction of lumbar kyphosis and lower incidence of back pain than nonoperatively managed cases. We recommend careful physical and radiographic examination of all patients with significant abrasion or bruising about the pelvis or abdomen related to seat belts. Victims of automobile crashes who are treated for bowel injury require thoracolumbar radiographs. Similarly, patients with Chance-type fractures should undergo diagnostic peritoneal lavage or computerized abdominal tomography.

Abdominal Injuries↗

PubMed1991

A statewide profile of general surgery trauma practice.

This study profiles the practices, experience, and viewpoints of general surgeons treating trauma patients throughout a state. A mail survey of the American College of Surgeons State Chapter membership was conducted. Response rate of general surgeons was 65%. Typically, the trauma surgeon is between 30 and 50 years old, having received formal trauma experience through residency training only. Thirty-nine per cent report current ATLS certification. Practices are most commonly based at a community hospital in an urban setting. Half of surgeons treating trauma operate at more than one hospital and nearly a third take call at more than one hospital simultaneously. Eighty-seven per cent of respondents reported trauma patients comprise less than one quarter of their practice. Most (68%) admitted fewer than 25 trauma patients to their service in the year before the survey and 78% reported performing less than ten trauma laparotomies in the prior year. Fifty-eight per cent disagree that every general surgeon should routinely manage major trauma and 83% feel that traumatology entails a specific body of knowledge and expertise. Of the various components of trauma care, the role of the surgeon in trauma prevention and administrative duties was ranked at least important. The areas of surgeon availability, uniformity of basic experience and adequate maintenance of skills need further analysis.

Adult↗

PubMed1991

The epidemiology of seatbelt-associated injuries.

This study examined the frequency of spine and abdominal injuries to motor vehicle occupant crash victims, the relationship between the two types of injuries, and the association with restraint use. There were 303 motor vehicle occupants treated at a regional trauma center for spine and/or abdominal injuries over a 5-year period. Patients with Chance-type fractures of the lumbar spine were much more likely to be rear seat passengers and to be using a lap belt than were patients with other types of spinal injuries. Similarly, patients with hollow viscus injuries were more likely to be rear seat passengers and to be lap belted than were patients with injuries to the spleen, liver, pancreas, or kidneys. Nearly two thirds of the lumbar Chance-type fractures were associated with hollow viscus injuries, including six of seven children. This increased risk of Chance-type fractures and hollow viscus injuries was associated with increased use of lap-belt seat restraints in the population.

Abdominal Injuries↗

PubMed1991

Validity of applying adult TRISS analysis to injured children.

Injury severity measures are becoming increasingly important for quality assurance and injury research. TRISS analysis, which uses the Revised Trauma Score (RTS) and Injury Severity Score (ISS) to predict survival, is an effective tool for comparing outcomes between trauma centers. It has been argued that blunt trauma outcome differs between children and adults, yet the Major Trauma Outcome Study (MTOS) adult data base (ages 15-54 years) regression weights have been used by others to calculate TRISS scores for injured children. This study appears to be the first to perform TRISS analysis on groups of children and adults treated by the same surgeons using the same treatment protocols to assess the validity of applying "adult" TRISS analysis to children. The charts of 346 consecutive children (ages 0-14) and 346 random adults (ages 15-54) admitted to a regional trauma center for isolated blunt trauma over a 30-month period were reviewed for demographics, mechanism of injury, RTS, ISS, and survival. Statistical evaluation included TRISS survival analysis and calculation of the Z statistic. The median ISS was 10 for both children and adults. The Z statistics for children and adults were similar (1.85 and 1.81). Analysis demonstrated the groups to be statistically identical with a nonsignificant trend toward improved survival compared with the MTOS baseline group. These data support the use of existing TRISS analysis for evaluation of pediatric trauma care.

Adolescent↗

PubMed1991

Reappraisal of emergency room thoracotomy in a changing environment.

The efficacy of resuscitative emergency room thoracotomy (ERT), particularly in blunt injury, has been questioned. Wide application of the procedure may not be cost effective. The risk of exposure and lethal infection to medical personnel during ERT is considerable. For the past decade, the policy at this institution has been to perform ERT on all moribund patients sustaining penetrating torso injury and all patients sustaining blunt injury with any evidence of cardiac electrical activity. To evaluate whether such a liberal policy is currently justified, the charts of all patients undergoing ERT over a 4-year period were reviewed. One hundred twelve patients underwent ERT; 24 (21%) sustained penetrating injury, 88 (79%) blunt injury. The overall survival rate was 1.8%. Penetrating injury had a 4.2% survival and blunt injury 1.1%. No patients with CPR initiated at the scene and required throughout transport survived. In those patients with both blood pressure and spontaneous respirations present in the field, survival rate was 11.8%. Survival rate in patients manifesting sinus rhythm or ventricular fibrillation upon arrival at the ER was 6.4%. No survivors were noted among patients coming to the hospital with an idioventricular rhythm or asystole. The total hospital charges for patients undergoing ERT exceeded reimbursement by $59,565. Screening for HIV and hepatitis could be documented in only two patients; both were negative. Liberal performance of ERT has dismal results, incurs monetary loss, and affords a greater potential for exposure to lethal infection. Emergency room thoracotomy is justified only when vital signs or a resuscitatible cardiac rhythm are present in the field or ER and deteriorate shortly before thoracotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1991

Pulmonary effects of continuous endotoxin infusion in the rat.

A major hindrance to the elucidation of the pathogenesis of the adult respiratory distress syndrome (ARDS) is the lack of an animal model consistent with the clinical course in humans. A continuous intravenous infusion of endotoxin (LPS) over a several day period was used to more closely parallel the clinical setting. Male Sprague-Dawley rats infused with LPS via indwelling right atrial catheters become tachypneic, lethargic and anorectic with a steady loss in body weight. Serial blood gas analyses demonstrate an early respiratory alkalosis followed by increasing acidosis and hypoxia. Lungs demonstrate 1) pulmonary leukoaggregation, 2) interstitial and intraalveolar edema, 3) Type I pneumocyte injury, 4) proliferation of Type II pneumocytes, and 5) thickening of the microvascular walls. Differential neutrophil count in bronchoalveolar lavage (BAL) fluid increased from 1% to a peak of 59.1% +/- 3.0% and protein content was elevated. A prolonged infusion of LPS in the rat produces a lung injury which mimics many of the pathophysiologic and histologic features associated with sepsis-induced ARDS in humans.

Animals↗

PubMed1990

Evaluation of the Pediatric Trauma Score.

A Pediatric Trauma Score (PTS) was recently developed and is rapidly gaining acceptance as a triage tool. This study examines the utility of the PTS as compared with the Revised Trauma Score, which is applicable to all ages. The charts of 376 children 0 to 14 years of age who were admitted to the trauma service of a level 1 trauma center were reviewed. Significant correlations were found for both the PTS and the Revised Trauma Score with survival, the Injury Severity Score, APACHE II score, vital signs, the Glasgow Coma Scale score, hematocrit, need for an operation, and number of days in an intensive care unit. The PTS was of no statistical advantage as compared with the Revised Trauma Score. Triage accuracy was 68.3% for the PTS and 78.8% for the Revised Trauma Score. The Revised Trauma Score is easy to use and universal in its applicability. The PTS involves learning a separate scoring system and is of no advantage.

Adolescent↗

PubMed1990

Endotoxin requirements for alveolar macrophage stimulation.

Acute pulmonary failure or ARDS in severely injured patients continues to be a significant problem. The most important clinical risk factor identified is sepsis syndrome. Sepsis syndrome is the clinical correlate of a malignant systemic inflammatory process and is directed in large part by the tissue-fixed macrophage (M phi), such as the alveolar M phi. The M phi is capable of producing most of the central inflammatory mediators responsible for the pathophysiology seen during sepsis and organ injury. Two major mediators are procoagulant activity (PCA), leading to diffuse microvascular thrombosis, and tumor necrosis factor (TNF), causing much of the physiologic derangement of sepsis. Endotoxins (LPS) derived from Gram-negative bacterial cell walls are the primary inflammatory stimulus for the tissue-fixed M phi production of inflammatory mediators. It is not completely known how LPS interacts with its various cellular targets, but it is hoped that knowledge of the molecular interactions involved in stimulation of the M phi by endotoxin will lead to therapies to modulate the response and prevent deleterious processes such as ARDS. In the present studies, LPS from E. coli 0111:B4 was shown in a dose response to stimulate large levels of both PCA and TNF in alveolar M phi. LPS from Bacteroides fragilis and Lipid X (the monosaccharide precursor of endotoxin) were unable to cause stimulation of the M phi in vitro. However, both moieties, B. fragilis LPS and Lipid X, were able to effectively and specifically compete with E. coli LPS and block M phi stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Oxidant-induced endothelial leak correlates with decreased cellular energy levels.

A common finding in oxidant-induced organ injury is loss of vascular endothelial cell (EC) integrity and subsequent leak. The mechanisms involved are unclear, but maintenance of EC structure and functional integrity is highly dependent on the EC energy level. This study investigates whether oxidant-induced EC injury and concomitant increased monolayer permeability correlate with decreased energy levels. Rabbit pulmonary microvascular EC in vitro were exposed to varying levels of glucose oxidase as an oxidant-generating source for 2 h. Permeability changes were determined by albumin-Evans blue dye exclusion by monolayers of EC. ATP (nm/10(6) cells) and energy charge [ATP + 1/2ADP/(ATP + ADP + AMP)] were determined by HPLC. ATP and energy charge were found to decrease as permeability increased in response to increasing glucose oxidase concentration. ATP levels were a significantly more sensitive predictor of increased permeability than was energy charge. At 24 h, both permeability and ATP levels returned toward baseline. It appears that cell energy charge is preserved despite significant increases in monolayer permeability.

Adenosine Diphosphate↗

PubMed1989

Human endothelial cell adhesiveness for neutrophils, induced by Escherichia coli lipopolysaccharide in vitro, is inhibited by Bacteroides fragilis lipopolysaccharide.

Recent studies in vitro have demonstrated that LPS from Gram-negative bacteria are capable of inducing endothelial cells to express a cell surface property that promotes the adherence of neutrophils (polymorphonuclear cells, PMN). We have investigated the effects of LPS from Bacteroides fragilis, an organism documented to have little toxicity in vivo, on the induction of this property in human endothelial cells. Monolayers of cultured human umbilical vein endothelial cells (HUVE) exhibited no increase in adhesiveness for 51Cr-radiolabeled PMN after 4 h of exposure to B. fragilis LPS from 1 ng to 10 micrograms/ml. Escherichia coli LPS elicited a dose-dependent enhancement of HUVE adhesiveness for PMN over the same concentration range, reaching a maximum of 49.4 +/- 6.6% at 10 micrograms/ml. Like E. coli LPS, B. fragilis LPS converted chromogenic substrate in the Limulus amebocyte lysate assay, and was directly cytotoxic to bovine aortic endothelial cells. Both B. fragilis LPS activities required doses two-to-three log-fold higher than for E. coli LPS. In addition, we found that B. fragilis LPS inhibited the induction of HUVE adhesiveness for PMN by E. coli LPS. This inhibition was also dose-dependent, becoming maximal (greater than 80%) when B. fragilis LPS was in 10- to 20-fold excess. Tumor necrosis factor and IL-1, two monokines which also elicit HUVE adhesiveness for PMN, were not inhibited by B. fragilis LPS, suggesting a mechanism of HUVE activation by LPS which is signal-specific, and which recognizes specificities of LPS structure.

Bacteroides fragilis↗

PubMed1989

Evaluation of potentially preventable deaths among pedestrian and bicyclist fatalities.

The prehospital, emergency department, and in-hospital care of 84 patients who died following a pedestrian- or bicycle-motor vehicle collision in a four-county area was retrospectively reviewed using a systematic, detailed scoring system. The purpose of the study was to examine the effectiveness of an advanced paramedic-regionalized trauma care system and to examine the usefulness of a systematic evaluation tool in identifying preventable and possibly preventable deaths. Among the 84 deaths, one was judged to be preventable and 18 possibly preventable. The one preventable death occurred in the emergency department, while the possibly preventable deaths more commonly occurred after 48 hours and were due to central nervous system injury, sepsis, and multiple organ failure. Prolonged prehospital and emergency department time and failure to establish an airway were the most common problems identified as contributing to fatal outcome. The use of explicit criteria was demonstrated to be an effective addition to the analysis of trauma care systems.

Accidents, Traffic↗

PubMed1989

Great expectations: stress and the medical family. 1987 Committee on Issues, Association for Academic Surgery.

The high divorce rate and significant stress experienced by families of academic surgeons stimulated the Committee on Issues of the Association of Academic Surgery to choose medical family stress as the topic for the 1987 Committee presentation at the annual meeting. The Committee hoped to provide insight into the cause of this stress and new strategies for coping with this pervasive problem. Forty-three percent of the 505 surgeons who entered the Association from 1981 through 1984 and 38% of their spouses responded to a questionnaire covering issues of time management, response to stress, child rearing, financial security, and spouse career. A panel consisting of Shirley P. Levine, M.D., Hiram C. Polk, Jr., M.D., and Lane A. Gerber, Ph.D., after discussing the questionnaire results, recommended realistic goal setting, specific prioritization of activities, recognition of the considerable contributions of the spouse, and insight into personal limitations as mechanisms for improving family function.

Female↗

PubMed1989

Protein kinase C: a potential pathway of endothelial cell activation by endotoxin, tumor necrosis factor, and interleukin-1.

Human endothelial cells exposed to lipopolysaccharide (LPS), tumor necrosis factor (TNF), or interleukin-1 (IL-1) in vitro acquire a cell surface property that promotes the adherence of neutrophils (PMNs). The common mechanism by which endothelial cells are activated by these agents is unknown. We examined adherence of PMNs to cultured human umbilical vein endothelium (HUVE) pretreated with LPS (100 ng/ml), TNF (100 U/ml), and IL-1 (1 U/ml) in medium alone or medium containing protein kinase inhibitors H-7 or HA-1004. Both compounds inhibit a similar spectrum of protein kinases, but H-7 is an effective inhibitor of protein kinase C, whereas HA-1004 is not. We found that H-7 (25 mumol/L) reduced the adherence of PMNs to LPS-, TNF-, and IL-1-stimulated HUVE monolayers to 16.7% +/- 3.0%, 12.1% +/- 2.5%, and 18.3% +/- 2.9% of control, respectively (mean plus or minus standard error of three experiments); HA-1004 (25 mumol/L) did not inhibit endothelial adhesiveness. Cytotoxicity of H-7 was less than 10% in LPS-, TNF-, and IL-1-treated HUVE. Protein synthesis, as measured by the incorporation of tritiated amino acids, was not significantly impaired in LPS-treated HUVE concurrently exposed to H-7. We conclude that protein kinase C appears to be a necessary common mediator of endothelial cell activation by LPS, TNF, and IL-1.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1989

Pediatric trauma: need for surgical management.

A recent proposal by some pediatricians is that they be primarily responsible for resuscitation and triage of injured children with surgical care being initiated only through consultation. To assess the need for operative intervention, a consecutive series of 376 children less than 15 years of age admitted to a regional trauma center was examined, in which 194 children had 254 operations. Mortality was 7.2%. Twenty-two children who presented with persistent hemodynamic instability (sys. BP less than 90 mm Hg) had a mortality of 73%. Children were divided into three severity groups based on the Revised Trauma Score (RTS). Of the severely injured children (RTS less than or equal to 6), 79% required emergent operative intervention; 42% and 14%, respectively, required emergent operation in the moderately (6 less than RTS less than 12) and minimally (RTS = 12) injured groups. The need for operative management is great, even in "minimally" injured children.

Child↗