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Biomedical subjects

R Demling

Publications and source records attributed to R Demling.

At least 19 recordsLinked to original sources
PubMed2000

Pulmonary artery catheterization and clinical outcomes: National Heart, Lung, and Blood Institute and Food and Drug Administration Workshop Report. Consensus Statement.

OBJECTIVE: The efficacy and safety of the pulmonary artery catheter are under scrutiny because of its association with increased morbidity and mortality in observational studies. In response, the National Heart, Lung, and Blood Institute (NHLBI) and the US Food and Drug Administration (FDA) conducted the Pulmonary Artery Catheterization and Clinical Outcomes workshop in Alexandria, Va, on August 25 and 26, 1997, to develop recommendations regarding actions to improve pulmonary artery catheter utility and safety. PARTICIPANTS: The NHLBI and FDA planning task force selected a workshop chairperson, subcommittee chairs, and participants. Approximately 85 participants were selected for their collective expertise in critical care, pulmonary medicine, cardiovascular medicine and surgery, pediatrics, nursing, biostatistics, and medical economics. The meeting was open to industry representatives and other government and lay observers. This workshop was funded by the NHLBI and the FDA's Division of Devices. EVIDENCE: Published reports relating to the efficacy and safety of the pulmonary artery catheter, especially consensus documents developed by professional societies. CONSENSUS PROCESS: The planning task force disseminated materials, held teleconferences, and developed draft position papers prior to the workshop. These were modified during the workshop and thereafter in the course of several teleconferences, and presented to the entire group for final modifications and approval. CONCLUSIONS: A need exists for collaborative education of physicians and nurses in performing, obtaining, and interpreting information from the use of pulmonary artery catheters. This effort should be led by professional societies, in collaboration with federal agencies, with the purpose of developing and disseminating standardized educational programs. Areas given high priority for clinical trials were pulmonary artery catheter use in persistent/refractory congestive heart failure, acute respiratory distress syndrome, severe sepsis and septic shock, and low-risk coronary artery bypass graft surgery. JAMA. 2000;283:2568-2572

Catheterization, Swan-Ganz↗
PubMed1998

Energy charge potential and glutathione levels as predictors of outcome following burn injury complicated by endotoxemia.

We studied the effect of water-soluble antioxidants geared at restoring glutathione levels on oxygen consumption, cell energetics as measured by energy charge potential (ECP), glutathione levels, and mortality, in response to a 20% total body surface area (TBSA) third degree burn injury combined with endotoxemia, five days after burn in a rat model. The 20% TBSA third degree burn injury was not fatal for the six day study period. Oxygen consumption as well as red blood cell ECP remained unchanged from control values. Liver ECP was significantly reduced; however, liver glutathione was significantly increased. The 20% TBSA burn injury combined with endotoxemia produced a 60% mortality rate. Twenty-four hour survivors (40%) demonstrated a significant decrease in oxygen consumption, red blood cell ECP, and liver ECP. Liver glutathione was significantly decreased compared with burn but was not significantly decreased compared with control. Nonsurvivors of the burn injury combined with endotoxin (60%) demonstrated a significant reduction in liver glutathione levels compared with survivors. Oxygen consumption and ECP could not be measured in the nonsurvivors due to the rapid loss of ATP in the moribund state that occurred by 4 h postinjury. Antioxidants produced 100% survival, attenuated in the fall in liver ECP, and restored red blood cell ECP and liver glutathione levels to normal values. We conclude that a modest burn injury combined with endotoxemia produces a liver glutathione debt, oxygen debt, an energy deficit, and 60% mortality. The mechanism of injury is oxidant related as antioxidants prevented mortality restored liver glutathione levels, and prevented or attenuated the decrease in ECP. A decrease in ECP and glutathione levels appear to be more sensitive indicators of outcome than the presence of an oxygen debt. The survivors, in both burn plus endotoxin groups treated with or without antioxidants was comparable, indicating a critical value for oxygen consumption exists before death occurs.

Animals↗
PubMed1998

Closure of the "non-healing wound" corresponds with correction of weight loss using the anabolic agent oxandrolone.

We studied the relationship between restoration of weight loss and healing of the "non-healing wound." Eight consecutive patients with large "non-healing wounds" of an average of 12 months duration, despite good local wound care, were studied. All had a weight loss of 10 percent or more of body weight, mainly lean body mass. Optimizing nutrition (4 weeks) did not significantly increase weight or healing. The addition of the oral anabolic agent oxandrolone increased restoration of weight (4 lbs/week) over a 12-week period. Five wounds completely closed and three closed by 75 percent during this period. We noted a significant correlation (r = 0.67) between restoration of weight loss and closure of the previously "non-healing wound." The rate of wound healing was most prominent after 50 percent of weight loss had been restored. This finding reflects the key relationship between restoring body weight, body protein stores, and wound healing.

Adult↗
PubMed1997

Management of a patient with advanced AIDS and toxic epidermal necrolysis using human growth hormone and G-CSF.

Toxic epidermal necrolysis (TEN) is a serious drug reaction that is occurring with increased frequency among those affected with HIV and AIDS. It carries a grave prognosis for those with advanced AIDS and massive skin involvement. We report a severe case of TEN treated with wound care, intravenous nutrition, human growth hormone (hgh), and granulocyte colony-stimulating factor (G-CSF).

Acquired Immunodeficiency Syndrome↗
PubMed1996

Fluid resuscitation with deferoxamine hetastarch complex attenuates the lung and systemic response to smoke inhalation.

BACKGROUND: We determined the effect of infusing the iron chelator deferoxamine complexed to hetastarch on the degree of lung dysfunction and systemic abnormalities produced by a severe smoke exposure. METHODS: Adult sheep were given a smoke exposure under anesthesia that produced a peak carboxyhemoglobin between 40% and 45%. Twenty-eight sheep were studied; eight were given smoke alone and resuscitated with sufficient lactated Ringer's solution to maintain baseline hemodynamics. Seven sheep were given a bolus plus 1 ml/kg/hr of a 10% deferoxamine-hetastarch solution for resuscitation; five were given hetastarch alone. The response was compared with eight controls during a period of 24 hours. RESULTS: Smoke alone and smoke with hetastarch resulted in a shunt fraction of greater than 25% and a 50% decrease in compliance, severe airway inflammation, mucosal slough, atelectasis, and some alveolar edema. Increased lipid peroxides measured as malondialdehyde were present in airway fluid. In addition, oxygen consumption increased by 100% early after injury, net 24-hour positive fluid balance was almost 3 L, and a significant increase occurred in liver lipid peroxidation. The group given deferoxamine had a significantly attenuated lung response, with only modest airway damage lung dysfunction, and minimal systemic changes including a net positive fluid balance of just over 1L and no liver lipid peroxidation. CONCLUSIONS: An iron chelator deferoxamine complexed to hetastarch, given after a severe smoke exposure, significantly attenuates the airway and the systemic inflammatory (oxidant) injury, indicating free iron release and subsequent increased oxidant activity to be a major etiologic factor.

Animals↗
PubMed1995

Alpha-tocopherol attenuates lung edema and lipid peroxidation caused by acute zymosan-induced peritonitis.

BACKGROUND: Inflammation-induced disease as seen with trauma and infection can lead to increased lung oxidant activity resulting in cell membrane lipid peroxidation. Acute zymosan-induced peritonitis in rats produces lung inflammation, edema, and lipid peroxidation. We determined whether administered alpha-tocopherol (vitamin E), the key antioxidant protection against cell membrane lipid peroxidation, would improve this process. METHODS: Male Wistar rats were given 0.75 mg/kg of intraperitoneal zymosan, volume resuscitated, monitored, and killed at 4 or 24 hours. Lung histologic changes and levels of conjugated dienes, a marker of lipid peroxidation, were used to monitor injury. The levels of vitamin E, vitamin C, and catalase were used to monitor antioxidant defenses. The effect of administering alpha-tocopherol (50 mg/kg) by gavage immediately after zymosan on the degree of the lung injury was then determined. RESULTS: Twenty-four hours after zymosan was administered, the vitamin E levels in plasma were significantly decreased, but lung tissue vitamin E levels were maintained, whereas tissue catalase and vitamin E levels decreased. Lung tissue-conjugated diene levels, alveolar edema, and neutrophil count were significantly increased. alpha-Tocopherol treatment increased the postzymosan plasma vitamin E levels by 50%. Lung tissue vitamin E levels did not increase; however, the degree of lung injury and lipid peroxidation was significantly attenuated. Tissue catalase levels were also maintained. CONCLUSIONS: We conclude that alpha-tocopherol given at the onset of a progressing inflammatory injury can protect the lung from oxidant damage and attenuate the degree of lung injury.

Acute Disease↗
PubMed1995

Effect of graded increases in smoke inhalation injury on the early systemic response to a body burn.

OBJECTIVE: To study the early (first 24 hrs) effect of increasing lung exposure to smoke on the hemodynamic response to a modest body burn. DESIGN: A prospective randomized study. SETTING: Laboratory at a university medical center. SUBJECTS: Thirty-two adult yearling female sheep. INTERVENTIONS: Adult sheep (n = 32) were given an 18% of body surface burn; 24 sheep were then exposed to cotton toweling smoke using 12 breaths of a tidal volume of 5, 10, or 20 mL/kg. Animals were awakened, resuscitated to baseline oxygen delivery, and then killed at 24 hrs. MEASUREMENTS AND MAIN RESULTS: Vascular pressure, cardiac output, and oxygen consumption and delivery were measured, as well as blood gases, lung and soft tissue lymph flow, and fluid balance. We found that a 5-mL/kg tidal volume smoke exposure x 12 breaths did not produce significant airway inflammation or alter the cardiopulmonary response to a burn alone. Oxygen consumption (VO2) remained at baseline and the net 24-hr positive fluid balance of 1.5 L was comparable to a burn alone. Increasing the smoke exposure to 10 mL/kg tidal volume, which produced a moderate airway injury, resulted in a significant increase in early fluid requirements, a 40% early increase in VO2, a doubling of positive fluid balance, as well as a marked increase in burn edema. However, gas exchange was not impaired. The 20-mL/kg tidal volume exposure resulted in an early 100% increase in VO2, a three-fold increase in fluid requirements at 1 to 4 hrs, compared with burn alone, in addition to a severe airway inflammation with mucosal slough and resulting impaired gas exchange. CONCLUSIONS: The addition of a smoke exposure which produces airway inflammation and injury significantly increases early post burn systemic metabolic demands and fluid requirements, as well as the degree of burn edema and positive fluid balance compared with a burn alone. The magnitude of the accentuated response appears to correspond with the degree of airway inflammation and not with alveolar dysfunction.

Animals↗
PubMed1995

Increased survival after major thermal injury: the effect of growth hormone therapy in adults.

BACKGROUND: Advances in the management of patients with major thermal injury have resulted in a progressive increase in survival rates. We report preliminary data evaluating the safety and potential efficacy of human growth hormone (HGH) administration in a high-risk population of burned patients. METHODS: From 1989 to 1993, 69 patients sustaining major burns (defined as patient age plus percentage of body surface area with deep second- and third-degree burns > or = 90) were evaluated. Patients routinely received anti-inflammatory pharmacotherapy including antioxidants, an endotoxin binder, and cyclooxygenase blockade. Half of the 54 patients who survived more than 7 days received HGH to enhance wound healing. Injury severity, morbidity, and mortality for patients receiving HGH was compared to the 27 patients not receiving HGH. RESULTS: For the entire population (n = 69), average age was 56 +/- 23 years, body surface area burned was 58% +/- 24%, and 30% sustained smoke inhalation. Actual mortality was 41%, significantly less than the more than 70% mortality rate predicted from reported outcome data. Patients receiving HGH were well matched with the group not receiving HGH with respect to extent of injury, burn management, pharmacotherapy, and in-hospital morbidity. Mortality of the patients receiving HGH was 11%, significantly less than the 37% mortality rate of the patients without HGH (p = 0.027). CONCLUSION: Compared to standard predictors of burn mortality our small patient group appears to have an improved survival rate, suggesting that the use of anti-inflammatory agents appears safe and potentially beneficial. Patients receiving HGH exhibited minimal drug-related complications and mortality rates were improved when this population was compared with both predicted mortality rates and a well-matched control population of concurrently treated patients. Prospective blinded trials are now necessary to confirm these findings in a larger patient group.

Adolescent↗
PubMed1994

Administration of large doses of vitamin C does not decrease oxidant-induced lung lipid peroxidation caused by bacterial-independent acute peritonitis.

Acute zymosan-induced peritonitis in rats produces lung inflammation and lipid peroxidation. The effect of this process on plasma and lung tissue ascorbic acid was determined, as was the effect of infusing 150 mg/kg of ascorbic acid immediately after zymosan on the degree of lung insult. Ascorbic acid levels were significantly decreased in plasma and lung tissue at 24 h after zymosan, and lung tissue conjugated diene and neutrophil content was also significantly increased. Vitamin C infusion increased postzymosan plasma levels by 50% over normal control levels. However, lung tissue ascorbic acid was still decreased, and no decrease in the lung injury process was noted. Added ascorbic acid also did not prevent a decrease in plasma vitamin E with the peritonitis. We conclude that the amount of ascorbic acid given in this study did not diminish the lung oxidant inflammatory changes. An insufficient dose or inadequate time for plasma ascorbic acid to equilibrate with the lung cytosol are possible explanations for the lack of attenuation of lung oxidant stress.

Acute Disease↗
PubMed1994

Changes in lung and systemic oxidant and antioxidant activity after smoke inhalation.

We determined the oxidant activity in lung airways, parenchyma, and systemic tissues in response to smoke inhalation, comparing lipid peroxidation with physiologic and histologic change. Adult sheep were given a controlled amount of cooled smoke from burned cotton toweling, containing a uniform particle diameter of 3-4 microns. The mean peak carboxyhemoglobin was 45 +/- 4%. Animals were monitored unanesthetized for 24 h and killed. Severe respiratory failure was noted, as a result of airways mucosal ulceration, submucosal edema, and atelectasis, along with increased airways fluid, but minimal alveolar edema. Airway fluid malondialdehyde (MDA) content was threefold greater than plasma. However, airways mucosa and lung parenchymal tissue, lipid peroxidation, and oxidized glutathione were not increased, suggesting the only direct oxidant activity was present only at the airways surface. Other factors besides oxidants are likely to be involved in the lung injury. However, a marked systemic oxidant stress was noted as evidenced by a significant increase in liver tissue MDA and decrease in reduced glutathione and catalase activity. The tissue oxidant stress also corresponded with a 75% increase in systemic oxygen consumption and an increase in soft tissue vascular permeability. We conclude that: 1) the only direct lung oxidant stress after smoke was noted in airways fluid, while lung tissue lipid peroxidation was not seen despite severe airways injury and atelectasis, and 2) major systemic physiologic changes, as evidenced by increased systemic oxygen demands and systemic microvascular permeability are seen with smoke exposure in addition to evidence of systemic tissue oxidant stress. The likely source of the oxidant activity was a smoke-induced systemic inflammation.

Animals↗
PubMed1994

Comparison of plasma reduced glutathione and oxidized glutathione with lung and liver tissue oxidant and antioxidant activity during acute inflammation.

We determined whether plasma levels of reduced glutathione (GSH) and oxidized glutathione (GSSG) accurately reflect the tissue GSH and GSSG levels in lung and liver during a progressive acute inflammation-induced increased oxidant activity. We also determined whether plasma GSH also reflected other antioxidant defenses. Male Wistar rats (n = 38) were given intraperitoneal zymosan (.75 mg/g body weight) producing an acute progressive peritonitis and generalized inflammation. Animals were resuscitated then killed at 4 or 24 h. Plasma and tissue levels of GSH, GSSG, vitamin C, alpha-tocopherol, and catalase were measured. Conjugated dienes and malondialdehyde were used as tissue markers of lipid peroxidation. We found lung and liver tissue GSH to be decreased significantly at 4 h while GSSG was increased. Lipid peroxidation was also present in the lung. At 24 h, GSH remained decreased in liver and GSSG remained increased in lung along with the lipid peroxides conjugated dienes and malondialdehyde. In addition, overall antioxidant defenses were decreased in both lung and liver. Plasma GSH remained decreased at 24 h corresponding with the decrease in liver GSH as well as the decrease in other plasma and tissue antioxidants. However, plasma GSSG levels were not significantly increased, at any time point, indicating plasma GSSG does not accurately reflect tissue oxidant activity.

Acute Disease↗
PubMed1994

Comparison between lung and liver lipid peroxidation and mortality after zymosan peritonitis in the rat.

We compared the mortality rate and the lung and liver histologic injury with the degree of tissue lipid peroxidation after zymosan-induced peritonitis. Male Wistar rats were given .75 or 1 mg/g of zymosan intraperitoneally and monitored for 24 h. Tissue lipid peroxides were measured as conjugated dienes and malondialdehyde (MDA) as were the antioxidants, ascorbic acid and catalase. Mortality rates for the .75 and 1 mg/g groups were 15 and 50%, respectively. In lung, the degree of increase in conjugated dienes and MDA was significantly greater in nonsurvivors than survivors. Ascorbic acid and catalase levels were also significantly decreased to a greater degree in the sicker animals with ascorbic acid decreased to a greater degree in the higher dose and sicker animals. The level of MDA corresponded with the degree of histologic change. Catalase decreased to a greater degree in liver than lung. We conclude that the degree of lung and liver lipid peroxidation correlates with the degree of inflammation induced tissue injury and mortality.

Analysis of Variance↗
PubMed1994

Effect of increasing the tidal volume of smoke breaths on smoke-induced lung dysfunction.

We determined the effect of a graded increase in lung exposure to a toxic smoke by increasing smoke tidal volume (VT) or the number of smoke breaths. Sheep were anesthetized and then insufflated with cooled cotton toweling smoke; VT was 5, 10, or 20 ml/kg, and smoke breaths were varied from 12 to 48. The smoke had a uniform particle size (3 +/- 0.4 microns diam). Peak carboxyhemoglobin levels varied from 8 +/- 2 to 45 +/- 4% in the lowest to highest exposure groups, respectively. Animals were monitored unanesthetized for 24 h, and then they were killed. Oxygenation (ratio of arterial PO2 to fraction of inspire O2) decreased from 480 +/- 21 to 200 Torr, and compliance decreased by approximately 50% in the highest smoke exposure groups, whereas only a modest decrease in oxygenation and no compliance changes were seen with lesser exposures. A moderate tracheobronchitis, some atelectasis, and no alveolar edema were noted in the lower smoke exposure groups, whereas severe tracheobronchitis, airway edema, and alveolar atelectasis were observed in the highest exposure group. Only modest alveolar flooding was noted. Impaired oxygenation and anatomic injury correlated best with the total smoke delivered (r = 0.59). Increasing VT from 5 to 20 ml/kg did not increase airway or alveolar injury if the total smoke mass delivered was maintained constant. The degree of impaired oxygenation did not correlate with measured lung water (r = 0.27) or lung lymph flow (r = 0.31).

Aerosols↗
PubMed1994

Smoke inhalation injury in sheep is caused by the particle phase, not the gas phase.

The inhalation of smoke can produce severe lung injury, particularly to airways. We assessed the role of the toxic compounds in the particle phase vs. those in the gas phase of smoke in the injury process by filtering out all particles > 0.3 micron diam before exposure. Adult sheep (n = 16) were insufflated with a well-characterized cellulose smoke. Mean particle size was 3 +/- 0.4 micron diam. A standardized dose of 12 breaths of whole or filtered smoke (n = 8/group) was given to sheep under anesthesia with a tidal volume of 20 ml/kg. Sheep were awakened and monitored for 24 h and then killed. Peak carboxyhemoglobin levels were 40-45% in both groups. Severe respiratory failure occurred only in the whole-smoke group, as evidenced by an increase in shunt fraction from a control of 0.04 +/- 0.02 to 0.28 +/- 0.05, a decrease in lung compliance of 50%, and histological evidence of severe airway mucosal edema, ulceration, and bronchorrhea. No significant physiological, histological, or biochemical changes were noted in the filtered-smoke group.

Animals↗
PubMed1994

Aerosolized deferoxamine prevents lung and systemic injury caused by smoke inhalation.

We assessed the role of oxidant release at the airway mucosal surface on airway injury and systemic response to a severe smoke insult. Adult sheep (n = 20) were insufflated with well-characterized smoke from burning cotton toweling. A standardized dose of 12 breaths of smoke with a tidal volume of 20 ml/kg was given under anesthesia. Sheep were awakened, monitored for 24 h, and killed; data were compared with control sheep. Sheep were given 1) humidified oxygen, 2) continuous aerosol of 10% deferoxamine (DFO)-pentastarch solution beginning after smoke, 3) DFO-alone aerosol, or 4) pentastarch-alone aerosol. DFO has antioxidant properties directly and chelates iron. Severe respiratory failure occurred in all but DFO-pentastarch group. Shunt fraction increased from a control of 4%. Histological assessment revealed severe airway mucosal edema, ulceration, bronchorrhea, and severe atelectasis but only moderate alveolar edema. Increased lipid peroxides were also noted in free airway fluid and in bronchoalveolar lavage fluid. In addition, oxygen consumption increased by 75%, fluid requirements increased threefold, and protein-rich systemic soft tissue lymph flow doubled, all significant increases compared with control sheep. No significant physiological or histological changes were noted in DFO-pentastarch aerosol group. We conclude that 1) oxidants possibly initiated through free iron release are involved in severe smoke-induced airway injury and resulting systemic inflammatory response, probably through an amplified oxidant injury and 2) an aerosol of a DFO-pentastarch complex prevents the injury process, whereas DFO alone is not effective as an aerosol.

Acute Disease↗
PubMed1994

Lung and systemic oxidant and antioxidant activity after graded smoke exposure in the rat.

We wanted to determine the effect of a graded smoke inhalation on lung and systemic oxidant stress, and its relationship to physiological and histological change. Male Wistar rats were given 12 breaths of 10 ml/kg (n = 8) (group 1) or 20 ml/kg (n = 8) (group 2) tidal volume, using cotton toweling smoke through the trachea using positive pressure. Rats were monitored, then killed at 24 hr. Data were compared to controls (n = 8). Peak group 1 and group 2 carboxyhemoglobins were 22 +/- 6 and 46 +/- 6%, with a mortality prior to 24 hr of 14% and 50%, respectively. Group 1 rats showed only moderate lung dysfunction but with severe airway inflammation and edema, alveolar inflammation and atelectasis, with a decrease in PaO2 from the control of 96 +/- 4 to 72 +/- 5 torr. No increase in lung, liver, or kidney oxidant-induced lipid peroxidation, measured as malondialdehyde lung, liver, or kidney oxidant-induced lipid peroxidation, measured as malondialdehyde (MDA), or decrease in the antioxidant defenses catalase was noted. Group 2 rats demonstrated severe airways edema, alveolar atelectasis, and alveolar edema, and a PaO2 decreasing below 60 torr, corresponding with a 3-fold increase in lung tissue MDA and 35% decrease in catalase. In addition, liver and kidney tissue MDA doubled, and catalase activity decreased by 40%. Increased oxygen consumption was also demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1994

Initial effect of smoke inhalation injury on oxygen consumption (response to positive pressure ventilation).

BACKGROUND: Our purpose was to determine the effect of a smoke inhalation injury on initial oxygen demands measured as oxygen consumption. In addition, we wanted to determine the effect of positive pressure ventilation (PPV) on this process. METHODS: Adult sheep were insuffated with cotton toweling smoke to a carboxyhemoglobin level of 45% +/- 3% and then monitored unanesthetized for 24 hours. Oxygen delivery was maintained at a constant state. RESULTS: A significant increase in oxygen consumption (VO2), indicating increased metabolic demands, occurred during the first 2 hours after smoke with peak increase of 75% +/- 10% above baseline. A second increase occurred peaking at 18 hours with a 40% +/- 11% increase. Both increases were due to increased O2 extraction from hemoglobin rather than increased cardiac output. Use of PPV during the first 2 hours had no effect on VO2 but did correct impaired lung function manifested by an increased shunt fraction. Use of PPV during the later increased VO2 totally reversed the process but had less effect on improving lung function. CONCLUSIONS: We concluded that the initial increase in oxygen demands is likely due to an acute release of inflammatory mediators from the airway injury. The PPV response is to reexpand airways and alveoli, but it has no effect on the metabolic response. The late increase is likely due to increased work of breathing, which is removed by PPV. However, lung dysfunction from established airway edema at this stage is less reversible with PPV.

Animals↗