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Biomedical subjects

C L Rice

Publications and source records attributed to C L Rice.

At least 19 recordsLinked to original sources

Liposome-encapsulated hemoglobin inhibits tumor necrosis factor release from rabbit alveolar macrophages by a posttranscriptional mechanism.

Macrophages contribute to the systemic inflammatory response that characterizes the sepsis syndrome through the production of inflammatory cytokines such as tumor necrosis factor (TNF). Liposome-encapsulated hemoglobin (LEH), a potential red cell substitute, is cleared by fixed tissue macrophages. In these studies, in vitro incubation of alveolar macrophages with stored LEH was shown to inhibit the expression of TNF induced by endotoxin (lipopolysaccharide, LPS) stimulation. This effect was dependent on LEH dose but independent of the period of exposure to the LEH. Despite inhibition of TNF expression, Northern blot analysis of total cellular RNA from LPS-stimulated macrophages revealed accumulations of TNF-specific transcripts in cells treated with or without LEH. Thus the mechanism of LEH inhibition of TNF expression appears to involve a posttranscriptional event. Although these results suggest a potential advantage of resuscitation with LEH when sepsis complicates hemorrhagic shock, immunomodulation in vivo remains to be defined.

Animals

Neuromuscular responses of patients with multiple sclerosis.

Muscle weakness, studied in 4 patients with multiple sclerosis (MS), was compared with values from normal subjects. Twitch occlusion showed that normal subjects could activate their muscles maximally, but patients rarely achieved greater than 60% activation. In both groups, motoneuron firing rates increased linearly with force. Consistent with the reduced level of activation, MCV firing rates in MS muscles rarely exceeded 17 Hz (compared with approximately 24 Hz for normals). However, for right and left muscles of one patient, mean maximum firing rates were 14.2 +/- 2 Hz and 8.0 +/- 2 Hz, but her muscles, could be activated to levels greater than 92% and 60%, respectively. This patient's ability to achieve higher than expected forces at low firing rates was probably due to her slow muscle contractile speeds, especially 1/2-relaxation time (75 to 115 ms, cf. approximately 60 ms for normals), and high twitch/tetanus ratio (0.4, cf. 0.2).

Adult

Sensitivity to endotoxin in rabbits is increased after hemorrhagic shock.

The immunoinflammatory response following trauma and hemorrhage may predispose to the development of sepsis and multiple-organ failure syndrome. Cardiac output (CO), arterial pressure, arterial PO2, and pulmonary permeability index were measured. We examined the sensitivity of rabbits to infusions of lipopolysaccharide (LPS) after hemorrhagic shock. Shock was produced by reducing CO to 40% of baseline for 90 min, followed by resuscitation with shed blood and then with lactated Ringer solution to maintain CO near baseline. Animals were assigned to three groups: 1) hemorrhagic shock only, 2) LPS only, and 3) hemorrhagic shock + LPS. Groups 1 and 3 were subjected to hemorrhagic shock on day 1. Escherichia coli LPS was infused (1.0 microgram/kg i.v.) into groups 2 and 3 on day 2. Fluid resuscitation with lactated Ringer solution was continued in an effort to maintain CO at baseline. Five hours after LPS infusion, 125I-albumin was injected intravenously, and rabbits were killed 1 h later for measurement of pulmonary permeability index. LPS infusion after shock (group 3) caused significant decreases in CO, arterial pressure, and PO2 and an increase in pulmonary permeability. These changes were not seen in the groups 1 and 2. We conclude that hemorrhagic shock and resuscitation result in a proinflammatory state, leading to increased sensitivity to subsequent exposure to LPS.

Animals

Role of leukocyte CD11/CD18 complex in endotoxic and septic shock in rabbits.

Two models of sepsis were investigated using rabbits. In the first model, rabbits given lipopolysaccharide (LPS) were treated with saline (group II) or CD18 monoclonal antibody (MAb) 60.3 (group III). Group I animals received no LPS. Cardiac output was maintained by infusion of lactated Ringer solution with group II (95 +/- 68 ml/kg) requiring significantly more than group I (0 +/- 0 ml/kg) or group III (39 +/- 27 ml/kg). Lung permeability indexes in groups II (median 0.002, range 0.023) and III (median 0.0035, range 0.053) were not different but were significantly greater than group I (median 0.0007, range 0.001). In the second model, peritonitis was produced by devascularizing the appendix, leaving it in situ for 19 h, and then performing an appendectomy. Saline or MAb 60.3 treatment was at appendectomy and every 12 h for 3 days. Survival was significantly greater in the MAb 60.3-treated group at day 10 (90 vs. 40%). Lung permeability was increased at day 2 and was not different between groups. Day 1 fluid requirements were greater in the saline-treated group. These data are consistent with MAb 60.3 protection of systemic but not pulmonary circulation in two models of sepsis.

Animals

Muscle temperature, contractile speed, and motoneuron firing rates during human voluntary contractions.

A study was made of motoneuron firing rates and mechanical contractile parameters during maximum voluntary contraction of human hand muscles. A comparison of muscles that had been fatigued after a 60-s maximum voluntary contraction (MVC) with muscles that were cooled by approximately 5 degrees C showed that the contractile properties, in particular the rates of contraction and relaxation, were similarly affected in both conditions. In contrast, the motoneuron firing rate was affected differently by the two treatments. In the case of the fatigued muscles the motoneuron firing rate was reduced by 36%, as was expected from previous studies, but in the case of the cooled muscles, there was no significant change in the motoneuron firing rate. We conclude that the reflex reduction in the motoneuron firing rate seen in the fatigued muscle is not triggered directly by a change in the mechanical properties of the muscle.

Adult

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

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

An analysis of the critical problem of trauma center reimbursement.

There is a widespread perception that many trauma centers are poorly reimbursed, and many hospitals that once cared for trauma victims no longer do so, primarily for financial reasons. The problem is blamed on both uninsured and underinsured patients, but data supporting this perception are lacking. To determine the validity of these perceptions and to better understand the nature of trauma center reimbursement, a survey was conducted. A questionnaire on the volume of trauma seen annually and the reimbursement experience for trauma center (TC) and hospital (HO) patient populations was mailed to representative but nonrandomly chosen trauma centers. Seventy-one surveys were mailed and 25 were returned (35%). There were 15 Level I and 10 Level II centers; 16 were urban, seven were suburban, and two were rural. Eighteen centers (72%) reported significant underfunding of the TC in contrast to the HO, and 11 indicated that they would not be able to continue their current level of TC services with present reimbursement. For Medicare patients, HO cost recovery rates averaged 93%, but recovery rates were only 64% for TCs. For Medicaid beneficiaries, the HO cost recovery rate averaged 85%, but it was only 49% for TCs. Thirty-one percent of TC patients had no insurance coverage at all, in contrast to only 9% of HO patients. An aggregate loss equal to 19.9% of total costs was reported by respondents. This survey, while not representative of trauma centers as a whole throughout the United States, does suggest that there is a basis for the perception of underfunding of trauma care and indicates that such underfunding results from the combination of adverse selection and disproportionate share. We also describe a new method for assessing and comparing trauma center reimbursement.

Data Collection

A CD18 monoclonal antibody increases the incidence and severity of subcutaneous abscess formation after high-dose Staphylococcus aureus injection in rabbits.

Monoclonal antibody (MAb) 60.3 blocks CD18-dependent polymorphonuclear neutrophil adherence to endothelium and has been shown to be of benefit in preventing tissue injury in a variety of inflammatory conditions. However, concern exists that interference with normal polymorphonuclear neutrophil host-defense functions may increase susceptibility to bacterial infection. We compared the development of subcutaneous Staphylococcus aureus abscesses in rabbits pretreated with MAb 60.3 to those pretreated with saline placebo. Bacterial inoculation with 10(6) or 10(7) colony-forming units (CFU) did not result in abscess formation in either control or antibody-treated groups. However, inoculation with 10(8) CFU resulted in more frequent and larger abscesses in antibody-treated rabbits than in controls. Abscess incidence was similar for inoculation with 10(9) CFU, although antibody-treated rabbits developed larger abscesses than did controls. The difference in abscess development is due to delayed leukocyte migration into inoculated tissue. The results of these experiments suggest that subjects treated with MAb 60.3 and exposed to massive S. aureus inocula may be at serious risk of infection. However, despite inhibited leukocyte adhesion, inocula of up to 10(7) CFU were well tolerated in this model. Whether these findings are clinically important remains to be determined, although exposure to bacterial concentrations of 10(8) CFU or greater occurs only rarely in clinical practice.

Abscess

Mechanisms and consequences of leukocyte-endothelial interaction.

Leukocyte adhesion to endothelium is a critical event in host defense against microorganisms and in the repair of tissue damage. Under some circumstances, however, altered leukocyte-endothelial interactions may contribute to the pathogenesis of inflammatory and immune diseases. In a number of experimental models, the inhibition of leukocyte adherence to endothelium substantially reduces vascular and tissue injury. Antiadhesion therapy may represent a novel approach to the treatment of a wide spectrum of clinical disorders.

Animals

Transient inhibition of neutrophil adherence with the anti-CD18 monoclonal antibody 60.3 does not increase mortality rates in abdominal sepsis.

Monoclonal antibodies (MAbs) that recognize the neutrophil (PMN) adherence complex CD11/CD18 inhibit PMN adherence to endothelium and attenuate PMN-mediated ischemia-reperfusion injury. One consideration regarding the clinical usefulness of such therapy is whether transient inhibition of PMN adherence or function will impede host defense and increase susceptibility to infection and sepsis. We studied susceptibility to sepsis in New Zealand white rabbits with an appendiceal devascularization model to answer the question: Does inhibition of PMN adherence with the anti-CD18 MAb 60.3 increase morbidity and mortality rates in abdominal sepsis? Four treatment groups of 10 animals each were studied: group 1 (controls) received no treatment, group 2 received MAb 60.3, group 3 was given the antibiotic cefazolin alone, and group 4 received both cefazolin and MAb 60.3. PMN emigration into the peritoneum was inhibited significantly in MAb 60.3-treated animals (groups 2 and 4). There was no difference in weight loss, incidence of infectious complications, or mortality rates when MAb 60.3-treated animals were compared with untreated animals. These results demonstrate that transient inhibition of PMN adherence does not increase morbidity or mortality rates in this model of abdominal sepsis. These results suggest that if MAb 60.3 or similar antibodies are used to prevent PMN-mediated injury, they will not increase susceptibility to sepsis.

Abdomen

Critical care air transportation of the severely injured: does long distance transport adversely affect survival?

Civilian aeromedical transportation systems, both fixed and rotary wing, have proliferated since the middle 1970s. However, outcome data substantiating the benefit of these services have been slow in coming. From February 22, 1982, through March 5, 1984, Airlift Northwest transported 118 trauma patients (aged 15 years and older) an average distance of 340 miles (range, 100 to 800 miles) with fixed-wing aircraft. The in-hospital mortality for this group was 19% compared with 18% for a comparable group of trauma patients who were ground-transported from within the city limits of Seattle, Washington. The two groups did not differ significantly in age, Injury Severity Score, or Glasgow Coma Score. These results suggest that some part of the clinical benefit of a regional trauma center may be extended up to 800 miles with no increase in transport-related mortality.

Adolescent

Inhibition of leukocyte adherence by anti-CD18 monoclonal antibody attenuates reperfusion injury in the rabbit ear.

Tissue injury resulting from ischemia and reperfusion forms the basis of several important disorders including myocardial infarction, stroke, and circulatory shock. To examine the role of neutrophils in this process and to determine the extent to which injury is a consequence of reperfusion, we utilized the monoclonal antibody 60.3, directed to CD18, the human leukocyte adherence glycoprotein, to block intravascular neutrophil aggregation and neutrophil adherence to endothelium in a rabbit model of tissue ischemia and reperfusion. Antibody treatment either before ischemia or after ischemia, but prior to reperfusion, resulted in the same degree of significant protection against endothelial, microvascular, and tissue injury. We conclude that neutrophils and increased neutrophil adhesiveness are important in the development of microvascular and tissue injury after ischemia and reperfusion and that under these circumstances, injury is primarily a consequence of reperfusion.

Animals

A comparison of anthropometry with computed tomography in limbs of young and aged men.

Arm and leg composition determined by anthropometry (AP, girths, and skinfolds) were compared with computed tomography (CT) in 7 young (mean age 31.4y) and 13 old (74.8y) males. Five transverse CT scans, girths, and skinfold measurements were made. In each CT image, total cross-sectional area (CSA), bone CSA, muscle compartment CSA, and "pure" muscle CSA within the compartment were measured. Corresponding volumes were also calculated. Total limb and muscle plus bone CSA and volumes were estimated from AP measures. The two methods were compared, and multiple regression analyses were used to predict component CSA and volumes from AP measures. In both groups, AP component measures in the leg provided more accurate values than in the arm. Skin plus subcutaneous tissue in the old was not well estimated by AP. The greater preponderance of nonmuscle tissue in the muscle compartments of the old, as determined from CT images, was not related to any AP estimates. Prediction equations for various component areas and volumes were derived. Some equations derived for the young could not be obtained for the old due to the reduced ability of AP to accurately assess limb composition of aged men.

Adult

The epidemiology of traumatic rupture of the thoracic aorta in children: a 13-year review.

Traumatic rupture of the thoracic aorta (TRA) is a rare but highly lethal injury in children that occurs as a result of car versus pedestrian accidents and motor vehicle accidents. TRA is often associated with life-threatening injuries to other organ systems. Therefore children with TRA like adults sustaining TRA must be treated urgently but systematically. The rarity of this injury makes it all the more important for physicians treating pediatric trauma victims to be cognizant of the importance of the injury and the clinical and radiographic signs. Even when TRA is promptly recognized in children it is associated with a high in-hospital mortality. The proper use of child restraint systems and adherence to the 55 M.P.H. speed limit may be important factors in reducing the mortality of TRA in children after MVA.

Accidents, Traffic

Inhibition of CD18-dependent neutrophil adherence reduces organ injury after hemorrhagic shock in primates.

Neutrophil adherence or aggregation may be important in the development of organ injury after hemorrhagic shock. Monoclonal antibody (MAb) 60.3 prevents both adherence and aggregation. Therefore we investigated MAb 60.3 treatment in prevention of organ injury after hemorrhagic shock in rhesus monkeys (Macaca mulatta). We performed esophagogastroscopy and placed catheters to measure cardiac output, mean arterial pressure, arterial blood gases, and urine output. Blood was removed to decrease CO to 30% of baseline for 90 minutes. Just before resuscitation, MAb 60.3 (2 mg/kg) or saline solution (control) was administered intravenously. Monitoring and fluid resuscitation continued for 24 hours, with lactated Ringer's solution given as a maintenance infusion (4 ml/kg/hr) plus additional lactated Ringer's solution to maintain CO at preshock levels. Esophagogastroscopy was repeated 24 hours after shock. There were two deaths in the control group at about 72 hours and none in the MAb 60.3 group. MAb 60.3-treated animals required less fluid (9.6 +/- 8.8 ml/kg vs 263.8 +/- 225.7 ml/kg), gained less weight (0.08 +/- 0.11 kg vs 0.70 +/- 0.37 kg), and maintained a higher hematocrit level (35.0% +/- 1.0% vs 26.9% +/- 4.9%). All five control animals had gastritis; MAb 60.3-treated animals had none (p less than 0.05; Fisher's exact test). Inhibition of neutrophil adherence or aggregation with MAb 60.3 at the time of resuscitation reduces fluid requirements and gastric injury in monkeys after hemorrhagic shock.

Animals

Hemodynamic effects of external cardiac massage in trauma shock.

The effectiveness of closed chest cardiopulmonary resuscitation (CCCPR) in maintaining cardiac output has been well studied in cardiac arrest. Trauma surgeons most often encounter shock secondary to hypovolemia or cardiac tamponade, and the effectiveness of CCCPR in that setting has not been established. To determine the hemodynamic effects of external massage in profound shock, hypotension was induced in baboons. Pressures obtained with external massage were compared to spontaneous intra-arterial pressures before compression. Although external massage increased systolic pressures in both tamponade and hypovolemia, diastolic pressures were consistently decreased. We conclude that CCCPR does not augment arterial pressure in the clinical situations associated with decreased LVEDV and is unlikely to provide organ perfusion for trauma victims.

Animals

Arm and leg composition determined by computed tomography in young and elderly men.

Five computed tomography (CT) scans were taken at measured intervals of the legs and arms of young (n = 7) and elderly (n = 13) men. Cross-sectional areas (CSA) of the total limb, muscle plus bone and bone were measured in each scan, and skin plus subcutaneous tissue areas were calculated by subtraction. In addition, in the arm scans the CSA of the extensor and flexor compartments were measured, and in the leg the CSA of the plantar flexor compartment. A value for lean muscle within these compartments was calculated by excluding non-muscle tissue using density measurements based on Hounsfield units. Related volumes for the various components were also calculated using geometric formulae. The results showed that elderly limbs were of a similar overall size as the young, but elderly muscles were smaller (28-36%) with greater amounts of non-muscle tissue located within a muscle, particularly in the plantar flexors (81% more than in the young). Elderly arms had a greater amount of skin plus subcutaneous tissue than the young, but there was no difference in the legs. Muscle volumes were similar to in vitro results reported from cadaver studies and can be predicted from single mid-limb CT scans using regression equations. These results illustrate that, due to the substantially reduced amount of 'pure' muscle tissue in the elderly, comparisons of relative strength with other populations may be misleading unless appropriate measurements of muscle size are considered. Methods to estimate in vivo physiological CSA, which is considered the best means of normalizing strength, have been demonstrated in this study.

Adult