American journal of critical care : an official publication, American Association of Critical-Care Nurses, 2015
Inhaled nitric oxide (iNO) is a rescue treatment for severe hypoxemia in the intensive care unit ... more Inhaled nitric oxide (iNO) is a rescue treatment for severe hypoxemia in the intensive care unit setting. To evaluate the effectiveness and safety of iNO in adult patients with severe hypoxemia before and during transport to a tertiary care center. Prospective data were examined in a retrospective cohort study. Patients with severe hypoxemia and cardiopulmonary failure (n=139) at referring hospitals in whom conventional therapy was unsuccessful were treated with iNO in the intensive care units in anticipation of transfer to a tertiary center. Treatment wih iNO was initiated by the critical care transport team in 114 patients and continued in 25 patients. Arterial blood gas analysis was done before and after iNO treatment. Patients treated with iNO had significant improvement in oxygenation: mean (SD) for PaO2 increased from 60.7 (20.2) to 72.3 (40.6) mm Hg (P=.008), and mean (SD) for ratio of PaO2 to fraction of inspired oxygen (P:F) increased from 62.4 (26.1) to 73.1 (42.6) (P= .03...
Damage-control resuscitation (DCR) has been advocated to reduce mortality in military and civilia... more Damage-control resuscitation (DCR) has been advocated to reduce mortality in military and civilian settings. However, DCR and excessive crystalloid resuscitation may be associated with a higher incidence of acute respiratory distress syndrome (ARDS). We sought to examine the impact of resuscitation strategies on ARDS development in combat casualty care. A retrospective review of Joint Theater Trauma Registry data on US combat casualties who received at least 1 U of blood product within the first 24 hours of care was performed, cross-referenced with the cohort receiving mechanical ventilation (n = 1,475). Massive transfusion (MT, ≥10 red blood cells [RBCs] and/or whole blood in 24 hours) and volume/ratios of plasma/RBC, platelet/RBC, and crystalloid/RBC (C/RBC, crystalloid liters/RBC units) were examined using bivariate/multivariate logistic regression and local regression analyses as ARDS risk factors, controlling for age, injury severity, admission systolic blood pressure, and Glasgow Coma Scale (GCS) score. ARDS was identified in 95 cases (6.4%). MT was required in 550 (37.3%) of the analysis cohort. ARDS was more common in MT (46 of 550, 8.4%) versus no-MT cohort (49 of 925, 5.3%), but mortality was not different (17.4% MT vs. 16.3% no-MT). ARDS patients received significantly increased crystalloid of blood product volumes. Increased crystalloid resuscitation (C/RBC ratio > 1.5) occurred in 479 (32.7%) of 1,464 patients. Unadjusted mortality was significantly increased in the cohort with C/RBC ratio of 1.5 or less compared with those with greater than 1.5 (19.1% vs. 6.3%, p < 0.0001), but no difference in ARDS (6.5% vs. 6.6%) was identified. Platelet/RBC ratio did not impact on ARDS. Increasing plasma (odds ratio, 1.07; p = 0.0062) and crystalloid (odds ratio, 1.04; p = 0.041) volumes were confirmed as independent ARDS risk factors. In modern combat casualty care, increased plasma and crystalloid infusion were identified as independent risk factors for ARDS. These findings support a practice of decreased plasma/crystalloid transfusion in trauma resuscitation once hemorrhage control is established to achieve the mortality benefit of DCR and ARDS prevention.
We have evaluated multiple factors inherent to an operating room-compatible endothelial cell proc... more We have evaluated multiple factors inherent to an operating room-compatible endothelial cell procurement and sodding procedure. Microvessel endothelial cell isolations have been performed on fat tissue obtained from over 140 patients with a 100% success rate. Liposuction-derived fat was optimal with respect to cell yield, and isolation time. The devices and equipment used were acceptable to the operating room and
Interfacility transport of patients on extracorporeal membrane oxygenation (ECMO) has been perfor... more Interfacility transport of patients on extracorporeal membrane oxygenation (ECMO) has been performed in large numbers at only a few programs. Limited data are available on outcomes after ECMO transport to justify expanding or discontinuing these programs. This was a retrospective review of a 20-year, single-institution experience with interhospital ECMO transport as well as a systematic review of reports of transfers of patients on ECMO. Results of both were compared with historical data from the international registry of the Extracorporeal Life Support Organization (ELSO). Between 1990 and 2012, ECMO was used to facilitate transport of 221 patients to our institution, and 135 (62%) survived to discharge. Review of an additional 27 case series describing ECMO transport of 643 patients showed an overall survival of 61%. After stratifying by age and primary indication for ECMO, survival of transported patients was not significantly different compared with all ECMO patients in the ELSO registry, with the exception of pediatric patients treated for respiratory failure (transported patients in this category had higher survival than those in the ELSO registry). Interfacility transport on ECMO is feasible and can be accomplished safely in the critically ill. Survival of transported patients is comparable to age-matched and treatment-matched ECMO patients at large.
The angiogenic basic fibroblast growth factor (bFGF) and vascular endothelial growth factor are i... more The angiogenic basic fibroblast growth factor (bFGF) and vascular endothelial growth factor are important in malignant breast epithelial growth. Nipple aspirate fluid (NAF) is a physiologic fluid collected noninvasively that contains proteins secreted by the breast ductal epithelium and may contain markers of breast cancer. The purpose of this study was to determine whether high concentrations of bFGF and vascular endothelial growth factor in NAF would be associated with in situ and invasive breast cancer, and whether prostate-specific antigen, a marker in NAF associated with breast cancer, would improve our ability to determine which subjects had the disease. Both bivariate and multivariate analyses were performed to determine the effects of race, menopausal status, bFGF concentration, and prostate-specific antigen on cancer risk. Bivariate analysis was also performed to determine the relationship between vascular endothelial growth factor concentration and cancer risk. Mean NAF bFGF levels were higher in women with breast cancer than in those without (19.2 vs 1.74 ng/g). Vascular endothelial growth factor was not associated with breast cancer. Race and menopausal status did not significantly affect the relationship between bFGF and cancer risk. bFGF, race, and menopausal status were each independent predictors of breast cancer, with bFGF being the most important. With knowledge of all three variables, the model was 89.9% sensitive and 69.0% specific in predicting which women had breast cancer. Adding prostate-specific antigen increased the sensitivity to 90.9% and the specificity to 83.3%. In subjects with NAF bFGF > 150 ng/g and prostate-specific antigen < 100 ng/g, 94.1% (32/34) of subjects had cancer. For women with NAF prostate-specific antigen > 100 ng/ g and bFGF < 150 ng/g, 90.5% were cancer free. bFGF concentration in NAF is directly associated with breast cancer, regardless of race and menopausal status. NAF bFGF may prove helpful in the early detection of breast cancer.
Granulomatous mastitis, a rare, benign breast condition characterized by granulomas and abscess f... more Granulomatous mastitis, a rare, benign breast condition characterized by granulomas and abscess formation, is mistaken frequently for inflammatory breast carcinoma. Although it has been reported in reproductive-age women, it is unusual in pregnancy. A 25-year-old black gravida 4 para 2 developed a tender, indurated 20 x 15 x 15 cm multilobulated breast mass at 17 weeks' gestation. After not responding to antibiotics and incisional drainage, the biopsy-proved granulomatous mastitis improved with corticosteroid treatment. A postpartum recurrence also responded to steroid therapy. Granulomatous mastitis is diagnosed clinically and histologically. Early recognition and initiation of steroid treatment might prevent repetitive, deforming breast biopsies.
The Journal of Trauma: Injury, Infection, and Critical Care, 2004
Wolters Kluwer Health may email you for journal alerts and information, but is committed to maint... more Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our Privacy Policy. ... Skip Navigation Links Home > March ...
Small-diameter (less than 6 mm) clinically available vascular grafts often fail due in part to th... more Small-diameter (less than 6 mm) clinically available vascular grafts often fail due in part to the inherent thrombogenicity of artificial polymers. Transplantation of endothelial cells onto the lumen of these vascular grafts has been suggested as one method to overcome this thrombogenicity. We have developed a compliant polyurethaneurea (PEUU) 4-mm graft with a luminal surface modified by a glow discharge gas plasma. Autologous microvessel endothelial cells were isolated from canine falciform ligament fat, were transplanted onto the luminal surface of the grafts using an intraoperative isolation and sodding technique, and both endothelial-cell-treated and non-cell-treated grafts were placed as bilateral carotid interposition grafts in a canine model. After 5 weeks of implantation, explanted control (non-cell-treated) grafts exhibited a deposition of platelets, white cells and fibrin characteristic of a thrombogenic surface. MVEC sodded grafts exhibited a multicellular lining within but distinct from the lumen of the PEUU graft. The blood-contacting surface of this lining exhibited an antithrombogenic endothelial cell monolayer. We suggest that the PEUU graft supported the initial deposition of MVEC and development of and endothelial cell lining. During the 5 weeks of implantation this lining continued to proliferate and detached from the PEUU graft substratum. The final neocellular lining exhibited a luminal diameter and histological features similar to a native artery.
Receptors for Escherichia coli heat-stable toxin (ST) are selectively expressed in membranes of i... more Receptors for Escherichia coli heat-stable toxin (ST) are selectively expressed in membranes of intestinal mucosa cells and colon carcinoma cells in vitro, suggesting their use as a marker for colorectal tumors in vivo. The present studies examined the expression and function of ST receptors in normal human tissues and primary and metastatic colorectal tumors obtained from patients at surgery. Surgical specimens were obtained as follows: from normal colon; from primary adenocarcinomas from all anatomic divisions of the colon and rectum; from gallbladder, kidney, liver, lung, lymph node, ovary, peritoneum, stomach; and from colon carcinomas metastatic to liver, lung, lymph node, ovary, and peritoneum. Membranes prepared from these specimens were assessed for the presence and functional characteristics of ST receptors. ST bound specifically to membranes from each division of normal colon and rectum and all primary and metastatic colorectal tumors examined. The affinity and density of ST receptors were similar in tumors of different grades and from various metastatic sites. ST-receptor interaction was coupled to activation of guanylyl cyclase in all normal samples of colon and rectum and all primary and metastatic colorectal tumors examined. In contrast, neither ST binding nor ST activation of guanylyl cyclase was detected in any extraintestinal tissues examined. Functional ST receptors are expressed in normal colonic tissue and primary and metastatic colorectal tumors but not by extraintestinal tissues in humans. Expression of ST receptors does not vary as a function of the metastatic site or grade of these tumors. Receptors expressed by colorectal tumors retain their characteristic function, with binding of ST coupled to activation of guanylyl cyclase. These studies support the suggestion that ST receptors represent a specific marker for human colorectal tumors that may have use as a target for directing diagnostics and therapeutics to these tumors in vivo.
Severe respiratory failure (including acute lung injury and acute respiratory distress syndrome) ... more Severe respiratory failure (including acute lung injury and acute respiratory distress syndrome) caused by 2009 H1N1 influenza infection has been reported worldwide. Refractory hypoxemia is a common finding in these patients and can be challenging to manage. This review focuses on nonventilatory strategies in the advanced treatment of severe respiratory failure and refractory hypoxemia such as that seen in patients with severe acute respiratory distress syndrome attributable to 2009 H1N1 influenza. Specific modalities covered include conservative fluid management, prone positioning, inhaled nitric oxide, inhaled vasodilatory prostaglandins, and extracorporeal membrane oxygenation and life support. Pharmacologic strategies (including steroids) investigated for the treatment of severe respiratory failure are also reviewed.
The use of sedatives, opioids, and neuromuscular blocking agents (NMBAs) may delay weaning and pr... more The use of sedatives, opioids, and neuromuscular blocking agents (NMBAs) may delay weaning and prolong intensive care unit length of stay. We hypothesized that in patients on higher positive end-expiratory pressure (PEEP), sedatives, opioids, and NMBAs are used in a higher proportion of patients and in higher doses and that the use of these medications is associated with prolongation of weaning and mortality. Retrospective analysis. The ALVEOLI trial. Five hundred forty-nine patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) who were enrolled in the ALVEOLI trial. We analyzed prospectively collected data regarding the impact of sedatives, opioids, and NMBAs in ALI/ARDS patients on duration of mechanical ventilation, time to weaning landmarks, and mortality. Sedatives and opioids were used in >80% of the patients in similar proportion in the two groups. The use of sedatives and opioids, but not the use of NMBAs, was associated with longer time on mechanical ventilation and an increased time to achieve a 2-hr spontaneous breathing trial (p < .0001). Sedatives were also associated with increased time to achieve unassisted breathing. NMBAs were used for a short period of time, in a higher proportion of patients in the lower PEEP group, and for a longer time (0.23 days). Sedatives and opioids use was similar in the higher and lower PEEP groups. The use of sedatives and opioids, but not NMBAs, was associated with a longer time to achieve important weaning landmarks.
Hospital-level variations in structure and process may affect clinical outcomes in ICUs. We sough... more Hospital-level variations in structure and process may affect clinical outcomes in ICUs. We sought to characterize the organizational structure, processes of care, use of protocols, and standardized outcomes in a large sample of U.S. ICUs. We surveyed 69 ICUs about organization, size, volume, staffing, processes of care, use of protocols, and annual ICU mortality. ICUs participating in the United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study. Sixty-nine intensivists completed the survey. We characterized structure and process variables across ICUs, investigated relationships between these variables and annual ICU mortality, and adjusted for illness severity using Acute Physiology and Chronic Health Evaluation II. Ninety-four ICU directors were invited to participate in the study and 69 ICUs (73%) were enrolled, of which 25 (36%) were medical, 24 (35%) were surgical, and 20 (29%) were of mixed type, and 64 (93%) were located in teaching hospitals with a median number of five trainees per ICU. Average annual ICU mortality was 10.8%, average Acute Physiology and Chronic Health Evaluation II score was 19.3, 58% were closed units, and 41% had a 24-hour in-house intensivist. In multivariable linear regression adjusted for Acute Physiology and Chronic Health Evaluation II and multiple ICU structure and process factors, annual ICU mortality was lower in surgical ICUs than in medical ICUs (5.6% lower [95% CI, 2.4-8.8%]) or mixed ICUs (4.5% lower [95% CI, 0.4-8.7%]). We also found a lower annual ICU mortality among ICUs that had a daily plan of care review (5.8% lower [95% CI, 1.6-10.0%]) and a lower bed-to-nurse ratio (1.8% lower when the ratio decreased from 2:1 to 1.5:1 [95% CI, 0.25-3.4%]). In contrast, 24-hour intensivist coverage (p = 0.89) and closed ICU status (p = 0.16) were not associated with a lower annual ICU mortality. In a sample of 69 ICUs, a daily plan of care review and a lower bed-to-nurse ratio were both associated with a lower annual ICU mortality. In contrast to 24-hour intensivist staffing, improvement in team communication is a low-cost, process-targeted intervention strategy that may improve clinical outcomes in ICU patients.
The prone position has been used to improve oxygenation in patients with severe hypoxemia and acu... more The prone position has been used to improve oxygenation in patients with severe hypoxemia and acute respiratory failure since 1974. All studies with the prone position document an improvement in systemic oxygenation in 70% to 80% of patients with acute respiratory distress syndrome (ARDS), with maximal improvement seen in the most hypoxemic patients. This article reviews data regarding efficacy for use of the prone position in patients with ARDS. Also described is a simple, safe, quick, and inexpensive procedure used to prone patients with severe ARDS on a standard bed in the intensive care unit at the University of Michigan.
American journal of critical care : an official publication, American Association of Critical-Care Nurses, 2015
Inhaled nitric oxide (iNO) is a rescue treatment for severe hypoxemia in the intensive care unit ... more Inhaled nitric oxide (iNO) is a rescue treatment for severe hypoxemia in the intensive care unit setting. To evaluate the effectiveness and safety of iNO in adult patients with severe hypoxemia before and during transport to a tertiary care center. Prospective data were examined in a retrospective cohort study. Patients with severe hypoxemia and cardiopulmonary failure (n=139) at referring hospitals in whom conventional therapy was unsuccessful were treated with iNO in the intensive care units in anticipation of transfer to a tertiary center. Treatment wih iNO was initiated by the critical care transport team in 114 patients and continued in 25 patients. Arterial blood gas analysis was done before and after iNO treatment. Patients treated with iNO had significant improvement in oxygenation: mean (SD) for PaO2 increased from 60.7 (20.2) to 72.3 (40.6) mm Hg (P=.008), and mean (SD) for ratio of PaO2 to fraction of inspired oxygen (P:F) increased from 62.4 (26.1) to 73.1 (42.6) (P= .03...
Damage-control resuscitation (DCR) has been advocated to reduce mortality in military and civilia... more Damage-control resuscitation (DCR) has been advocated to reduce mortality in military and civilian settings. However, DCR and excessive crystalloid resuscitation may be associated with a higher incidence of acute respiratory distress syndrome (ARDS). We sought to examine the impact of resuscitation strategies on ARDS development in combat casualty care. A retrospective review of Joint Theater Trauma Registry data on US combat casualties who received at least 1 U of blood product within the first 24 hours of care was performed, cross-referenced with the cohort receiving mechanical ventilation (n = 1,475). Massive transfusion (MT, ≥10 red blood cells [RBCs] and/or whole blood in 24 hours) and volume/ratios of plasma/RBC, platelet/RBC, and crystalloid/RBC (C/RBC, crystalloid liters/RBC units) were examined using bivariate/multivariate logistic regression and local regression analyses as ARDS risk factors, controlling for age, injury severity, admission systolic blood pressure, and Glasgow Coma Scale (GCS) score. ARDS was identified in 95 cases (6.4%). MT was required in 550 (37.3%) of the analysis cohort. ARDS was more common in MT (46 of 550, 8.4%) versus no-MT cohort (49 of 925, 5.3%), but mortality was not different (17.4% MT vs. 16.3% no-MT). ARDS patients received significantly increased crystalloid of blood product volumes. Increased crystalloid resuscitation (C/RBC ratio > 1.5) occurred in 479 (32.7%) of 1,464 patients. Unadjusted mortality was significantly increased in the cohort with C/RBC ratio of 1.5 or less compared with those with greater than 1.5 (19.1% vs. 6.3%, p < 0.0001), but no difference in ARDS (6.5% vs. 6.6%) was identified. Platelet/RBC ratio did not impact on ARDS. Increasing plasma (odds ratio, 1.07; p = 0.0062) and crystalloid (odds ratio, 1.04; p = 0.041) volumes were confirmed as independent ARDS risk factors. In modern combat casualty care, increased plasma and crystalloid infusion were identified as independent risk factors for ARDS. These findings support a practice of decreased plasma/crystalloid transfusion in trauma resuscitation once hemorrhage control is established to achieve the mortality benefit of DCR and ARDS prevention.
We have evaluated multiple factors inherent to an operating room-compatible endothelial cell proc... more We have evaluated multiple factors inherent to an operating room-compatible endothelial cell procurement and sodding procedure. Microvessel endothelial cell isolations have been performed on fat tissue obtained from over 140 patients with a 100% success rate. Liposuction-derived fat was optimal with respect to cell yield, and isolation time. The devices and equipment used were acceptable to the operating room and
Interfacility transport of patients on extracorporeal membrane oxygenation (ECMO) has been perfor... more Interfacility transport of patients on extracorporeal membrane oxygenation (ECMO) has been performed in large numbers at only a few programs. Limited data are available on outcomes after ECMO transport to justify expanding or discontinuing these programs. This was a retrospective review of a 20-year, single-institution experience with interhospital ECMO transport as well as a systematic review of reports of transfers of patients on ECMO. Results of both were compared with historical data from the international registry of the Extracorporeal Life Support Organization (ELSO). Between 1990 and 2012, ECMO was used to facilitate transport of 221 patients to our institution, and 135 (62%) survived to discharge. Review of an additional 27 case series describing ECMO transport of 643 patients showed an overall survival of 61%. After stratifying by age and primary indication for ECMO, survival of transported patients was not significantly different compared with all ECMO patients in the ELSO registry, with the exception of pediatric patients treated for respiratory failure (transported patients in this category had higher survival than those in the ELSO registry). Interfacility transport on ECMO is feasible and can be accomplished safely in the critically ill. Survival of transported patients is comparable to age-matched and treatment-matched ECMO patients at large.
The angiogenic basic fibroblast growth factor (bFGF) and vascular endothelial growth factor are i... more The angiogenic basic fibroblast growth factor (bFGF) and vascular endothelial growth factor are important in malignant breast epithelial growth. Nipple aspirate fluid (NAF) is a physiologic fluid collected noninvasively that contains proteins secreted by the breast ductal epithelium and may contain markers of breast cancer. The purpose of this study was to determine whether high concentrations of bFGF and vascular endothelial growth factor in NAF would be associated with in situ and invasive breast cancer, and whether prostate-specific antigen, a marker in NAF associated with breast cancer, would improve our ability to determine which subjects had the disease. Both bivariate and multivariate analyses were performed to determine the effects of race, menopausal status, bFGF concentration, and prostate-specific antigen on cancer risk. Bivariate analysis was also performed to determine the relationship between vascular endothelial growth factor concentration and cancer risk. Mean NAF bFGF levels were higher in women with breast cancer than in those without (19.2 vs 1.74 ng/g). Vascular endothelial growth factor was not associated with breast cancer. Race and menopausal status did not significantly affect the relationship between bFGF and cancer risk. bFGF, race, and menopausal status were each independent predictors of breast cancer, with bFGF being the most important. With knowledge of all three variables, the model was 89.9% sensitive and 69.0% specific in predicting which women had breast cancer. Adding prostate-specific antigen increased the sensitivity to 90.9% and the specificity to 83.3%. In subjects with NAF bFGF > 150 ng/g and prostate-specific antigen < 100 ng/g, 94.1% (32/34) of subjects had cancer. For women with NAF prostate-specific antigen > 100 ng/ g and bFGF < 150 ng/g, 90.5% were cancer free. bFGF concentration in NAF is directly associated with breast cancer, regardless of race and menopausal status. NAF bFGF may prove helpful in the early detection of breast cancer.
Granulomatous mastitis, a rare, benign breast condition characterized by granulomas and abscess f... more Granulomatous mastitis, a rare, benign breast condition characterized by granulomas and abscess formation, is mistaken frequently for inflammatory breast carcinoma. Although it has been reported in reproductive-age women, it is unusual in pregnancy. A 25-year-old black gravida 4 para 2 developed a tender, indurated 20 x 15 x 15 cm multilobulated breast mass at 17 weeks' gestation. After not responding to antibiotics and incisional drainage, the biopsy-proved granulomatous mastitis improved with corticosteroid treatment. A postpartum recurrence also responded to steroid therapy. Granulomatous mastitis is diagnosed clinically and histologically. Early recognition and initiation of steroid treatment might prevent repetitive, deforming breast biopsies.
The Journal of Trauma: Injury, Infection, and Critical Care, 2004
Wolters Kluwer Health may email you for journal alerts and information, but is committed to maint... more Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our Privacy Policy. ... Skip Navigation Links Home > March ...
Small-diameter (less than 6 mm) clinically available vascular grafts often fail due in part to th... more Small-diameter (less than 6 mm) clinically available vascular grafts often fail due in part to the inherent thrombogenicity of artificial polymers. Transplantation of endothelial cells onto the lumen of these vascular grafts has been suggested as one method to overcome this thrombogenicity. We have developed a compliant polyurethaneurea (PEUU) 4-mm graft with a luminal surface modified by a glow discharge gas plasma. Autologous microvessel endothelial cells were isolated from canine falciform ligament fat, were transplanted onto the luminal surface of the grafts using an intraoperative isolation and sodding technique, and both endothelial-cell-treated and non-cell-treated grafts were placed as bilateral carotid interposition grafts in a canine model. After 5 weeks of implantation, explanted control (non-cell-treated) grafts exhibited a deposition of platelets, white cells and fibrin characteristic of a thrombogenic surface. MVEC sodded grafts exhibited a multicellular lining within but distinct from the lumen of the PEUU graft. The blood-contacting surface of this lining exhibited an antithrombogenic endothelial cell monolayer. We suggest that the PEUU graft supported the initial deposition of MVEC and development of and endothelial cell lining. During the 5 weeks of implantation this lining continued to proliferate and detached from the PEUU graft substratum. The final neocellular lining exhibited a luminal diameter and histological features similar to a native artery.
Receptors for Escherichia coli heat-stable toxin (ST) are selectively expressed in membranes of i... more Receptors for Escherichia coli heat-stable toxin (ST) are selectively expressed in membranes of intestinal mucosa cells and colon carcinoma cells in vitro, suggesting their use as a marker for colorectal tumors in vivo. The present studies examined the expression and function of ST receptors in normal human tissues and primary and metastatic colorectal tumors obtained from patients at surgery. Surgical specimens were obtained as follows: from normal colon; from primary adenocarcinomas from all anatomic divisions of the colon and rectum; from gallbladder, kidney, liver, lung, lymph node, ovary, peritoneum, stomach; and from colon carcinomas metastatic to liver, lung, lymph node, ovary, and peritoneum. Membranes prepared from these specimens were assessed for the presence and functional characteristics of ST receptors. ST bound specifically to membranes from each division of normal colon and rectum and all primary and metastatic colorectal tumors examined. The affinity and density of ST receptors were similar in tumors of different grades and from various metastatic sites. ST-receptor interaction was coupled to activation of guanylyl cyclase in all normal samples of colon and rectum and all primary and metastatic colorectal tumors examined. In contrast, neither ST binding nor ST activation of guanylyl cyclase was detected in any extraintestinal tissues examined. Functional ST receptors are expressed in normal colonic tissue and primary and metastatic colorectal tumors but not by extraintestinal tissues in humans. Expression of ST receptors does not vary as a function of the metastatic site or grade of these tumors. Receptors expressed by colorectal tumors retain their characteristic function, with binding of ST coupled to activation of guanylyl cyclase. These studies support the suggestion that ST receptors represent a specific marker for human colorectal tumors that may have use as a target for directing diagnostics and therapeutics to these tumors in vivo.
Severe respiratory failure (including acute lung injury and acute respiratory distress syndrome) ... more Severe respiratory failure (including acute lung injury and acute respiratory distress syndrome) caused by 2009 H1N1 influenza infection has been reported worldwide. Refractory hypoxemia is a common finding in these patients and can be challenging to manage. This review focuses on nonventilatory strategies in the advanced treatment of severe respiratory failure and refractory hypoxemia such as that seen in patients with severe acute respiratory distress syndrome attributable to 2009 H1N1 influenza. Specific modalities covered include conservative fluid management, prone positioning, inhaled nitric oxide, inhaled vasodilatory prostaglandins, and extracorporeal membrane oxygenation and life support. Pharmacologic strategies (including steroids) investigated for the treatment of severe respiratory failure are also reviewed.
The use of sedatives, opioids, and neuromuscular blocking agents (NMBAs) may delay weaning and pr... more The use of sedatives, opioids, and neuromuscular blocking agents (NMBAs) may delay weaning and prolong intensive care unit length of stay. We hypothesized that in patients on higher positive end-expiratory pressure (PEEP), sedatives, opioids, and NMBAs are used in a higher proportion of patients and in higher doses and that the use of these medications is associated with prolongation of weaning and mortality. Retrospective analysis. The ALVEOLI trial. Five hundred forty-nine patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) who were enrolled in the ALVEOLI trial. We analyzed prospectively collected data regarding the impact of sedatives, opioids, and NMBAs in ALI/ARDS patients on duration of mechanical ventilation, time to weaning landmarks, and mortality. Sedatives and opioids were used in >80% of the patients in similar proportion in the two groups. The use of sedatives and opioids, but not the use of NMBAs, was associated with longer time on mechanical ventilation and an increased time to achieve a 2-hr spontaneous breathing trial (p < .0001). Sedatives were also associated with increased time to achieve unassisted breathing. NMBAs were used for a short period of time, in a higher proportion of patients in the lower PEEP group, and for a longer time (0.23 days). Sedatives and opioids use was similar in the higher and lower PEEP groups. The use of sedatives and opioids, but not NMBAs, was associated with a longer time to achieve important weaning landmarks.
Hospital-level variations in structure and process may affect clinical outcomes in ICUs. We sough... more Hospital-level variations in structure and process may affect clinical outcomes in ICUs. We sought to characterize the organizational structure, processes of care, use of protocols, and standardized outcomes in a large sample of U.S. ICUs. We surveyed 69 ICUs about organization, size, volume, staffing, processes of care, use of protocols, and annual ICU mortality. ICUs participating in the United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study. Sixty-nine intensivists completed the survey. We characterized structure and process variables across ICUs, investigated relationships between these variables and annual ICU mortality, and adjusted for illness severity using Acute Physiology and Chronic Health Evaluation II. Ninety-four ICU directors were invited to participate in the study and 69 ICUs (73%) were enrolled, of which 25 (36%) were medical, 24 (35%) were surgical, and 20 (29%) were of mixed type, and 64 (93%) were located in teaching hospitals with a median number of five trainees per ICU. Average annual ICU mortality was 10.8%, average Acute Physiology and Chronic Health Evaluation II score was 19.3, 58% were closed units, and 41% had a 24-hour in-house intensivist. In multivariable linear regression adjusted for Acute Physiology and Chronic Health Evaluation II and multiple ICU structure and process factors, annual ICU mortality was lower in surgical ICUs than in medical ICUs (5.6% lower [95% CI, 2.4-8.8%]) or mixed ICUs (4.5% lower [95% CI, 0.4-8.7%]). We also found a lower annual ICU mortality among ICUs that had a daily plan of care review (5.8% lower [95% CI, 1.6-10.0%]) and a lower bed-to-nurse ratio (1.8% lower when the ratio decreased from 2:1 to 1.5:1 [95% CI, 0.25-3.4%]). In contrast, 24-hour intensivist coverage (p = 0.89) and closed ICU status (p = 0.16) were not associated with a lower annual ICU mortality. In a sample of 69 ICUs, a daily plan of care review and a lower bed-to-nurse ratio were both associated with a lower annual ICU mortality. In contrast to 24-hour intensivist staffing, improvement in team communication is a low-cost, process-targeted intervention strategy that may improve clinical outcomes in ICU patients.
The prone position has been used to improve oxygenation in patients with severe hypoxemia and acu... more The prone position has been used to improve oxygenation in patients with severe hypoxemia and acute respiratory failure since 1974. All studies with the prone position document an improvement in systemic oxygenation in 70% to 80% of patients with acute respiratory distress syndrome (ARDS), with maximal improvement seen in the most hypoxemic patients. This article reviews data regarding efficacy for use of the prone position in patients with ARDS. Also described is a simple, safe, quick, and inexpensive procedure used to prone patients with severe ARDS on a standard bed in the intensive care unit at the University of Michigan.
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