Biomedical subjects

Mark R Hemmila

Publications and source records attributed to Mark R Hemmila.

14 recordsLinked to original sources

PubMed2005

Lipopolysaccharide-binding protein modulates acetaminophen-induced liver injury in mice.

Acetaminophen toxicity is the most common cause of acute liver failure in the United States and Europe. Although much is known about the metabolism of acetaminophen, many questions remain regarding the pathogenesis of liver injury. In this study, we examined the role of lipopolysaccharide-binding protein (LBP), a protein important in mediating cellular response to lipopolysaccharides, by using LBP wild-type and knockout (KO) mice. We found that LBP KO mice were protected from acetaminophen-induced hepatotoxicity. At 350 mg/kg of acetaminophen, LBP KO mice had significantly less liver injury and necrosis than wild-type mice. Repletion studies in LBP KO mice using an LBP-adenoviral construct resulted in significantly more hepatic injury and necrosis after acetaminophen exposure compared with mice receiving the control adenoviral construct. In conclusion, LBP KO mice are protected from toxicity with a decrease in hepatic necrosis following acetaminophen challenge. This suggests a novel role for LBP in modulating acetaminophen-induced liver injury. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/O270-9139/suppmat/index.html).

Acetaminophen↗

PubMed2005

Herb and vitamin supplementation use among a general ophthalmology practice population.

PURPOSE: To survey comprehensive ophthalmology patients about their use of vitamins and herbal supplements. DESIGN: Cross-sectional survey. METHODS: A survey instrument was developed and distributed to 397 patients presenting to a main campus university-based comprehensive ophthalmology clinic and to an off-site comprehensive ophthalmology clinic. Information gathered included demographics, use of prescription medications, use of vitamin and herbal supplements, the reasons for using these supplements, perceived benefits of these products, where the information regarding them was gathered, and with whom patients had discussed their use. RESULTS: Fifty-eight percent of patients reported nearly daily use of vitamins. Multivitamins were the most common vitamin and were used by 46% of the patients. Eight percent of patients used herbal products on a daily basis. Twenty-six percent learned about vitamins from their primary care physician (PCP), and just 2% from their ophthalmologists, while 35% discussed their actual use with a PCP, and 5% with their ophthalmologists. Just 2% of these patients learned of herbs from a PCP, and <1% from an ophthalmologist. Older patients used multivitamins and other vitamins most frequently, while gender and education were not predictive of vitamin or herbal use. Mean monthly spending on vitamins by users was 15.74 dollars, while herbal users spent a monthly mean of 15.35 dollars. CONCLUSIONS: Vitamins and herbs are used by a significant number of patients in a comprehensive ophthalmology setting. Given the prevalence of vitamin and herbal use, ophthalmologists should systematically inquire about their use.

Adolescent↗

PubMed2005

Extracorporeal support for organ donation after cardiac death effectively expands the donor pool.

BACKGROUND: We sought to evaluate the effect on short-term outcomes of normothermic, extracorporeal perfusion (ECMO) for donation of abdominal organs for transplantation after cardiac death (DCD). Study parameters included increase in number of donors and organs, types of organs procured, and viability of kidneys transplanted. METHODS: We retrospectively reviewed medical record data for all patients enrolled in our ECMO-supported DCD donor protocol between 10/1/2000 to 2/01/2004. We also reviewed the records for all patients undergoing organ donation after brain-death (DBD) during the study period at our institution. Recipient data were obtained and analyzed for all kidneys procured from both groups. RESULTS: Twenty patients were enrolled in our DCD protocol and underwent attempted organ donation. Fifteen patients completed the protocol; 3 maintained cardiac function throughout the prescribed 60 minutes after withdrawal of life support, and two patients' organs were deemed unsuitable for transplantation. Fourteen (70%) of the DCD donor patients originated on the trauma service and six (30%) were from other clinical services. The DCD program increased the potential donor pool by 33% (61 versus 81 patients) and the number of kidneys transplanted by 24% (100 versus 124). A total of 24 kidney, 5 liver, and 1 pancreas transplants were performed with these organs. Two of 24 (8.3%) DCD kidneys had delayed graft function. There were no perioperative rejection episodes or deaths. CONCLUSION: The implementation of a DCD protocol using extracorporeal perfusion increased the potential organ donor pool at our institution by 33%. This was accomplished without short term adverse effect on organ function compared with kidneys transplanted from DBD donors.

Adolescent↗

PubMed2005

Improved survival in mice given systemic gene therapy in a gram negative pneumonia model.

BACKGROUND: We previously demonstrated an essential role for lipopolysaccharide binding protein (LBP) in the pulmonary immune response to Gram-negative bacterial infection. LBP knockout mice had significantly higher mortality, greater rates of bacteremia, and higher counts of viable bacteria in their lungs at sacrifice compared with wild-type controls. We postulate that systemic LBP gene therapy will reconstitute a protective innate immune response in LBP knockout mice and that overexpression of LBP in wild-type mice may offer a survival advantage. METHODS: 12-16 week old female C57BL/6 wild-type mice and age matched LBP knockout mice were given 5 x 10(9) PFU of recombinant adenovirus containing either the gene for LBP or the irrelevant control protein beta-galactosidase by tail vein injection. 72 hours later each mouse was administered 1 x 10(3) CFU of Klebsiella pneumoniae by intratracheal injection. RESULTS: Administration of LBP by systemic gene therapy to LBP knockout mice improved survival from Klebsiella pneumonia to a level equivalent or better than wild-type mice exposed to the same dose of bacteria (36 versus 25%). Wild-type mice given the LBP gene therapy demonstrated increased 7 day survival from Klebsiella pneumonia when compared with controls treated with beta-galactosidase (68 versus 30%, p = 0.03). CONCLUSIONS: Systemic gene therapy with intravenous adenoviral vector transfer of LBP significantly improves survival in LBP knockout mice. Overexpression of LBP in wild-type mice improves survival from Klebsiella pneumonia. Raising levels of LBP in the setting of Gram-negative pneumonia may be of therapeutic benefit.

Acute-Phase Proteins↗

PubMed2004

Blunt splenic injury: operation versus angiographic embolization.

BACKGROUND: Splenic injuries, like other blunt traumatic injuries, are increasingly treated with non-operative management. Angiographic embolization (AE) has emerged as an alternative modality for treatment of splenic injuries. We hypothesized that splenic embolization would lead to equivalent, if not improved, outcomes in terms of mortality, total costs, complications, and duration of stay. METHODS: A retrospective review of a prospective data set was performed for all adult splenic injuries admitted to our level I trauma center from 2000 through 2003. Demographics, number of red cell units, emergency department hemodynamics, costs, and outcomes were examined. The operative group included those who underwent computed tomography (CT) first then went to the operating room (OR) (CT+OR) or those who went directly to the OR. RESULTS: There were 25 CT+OR and 24 AE patients of 164 blunt splenic injuries. After univariate analysis, higher injury severity score (ISS), lower systolic blood pressure, lower pH, and higher packed red blood cell transfusions were associated with increased mortality and duration of stay. The splenic Abbreviated Injury Scale (AIS; mean +/- SD) was the same for AE compared to CT+OR patients (3.8 +/- 0.4 vs 3.5 +/- 0.9). Although the AE group was older (50 +/- 20 vs 36 +/- 13 years, P < .01), Glasgow Comma Score (13 +/- 4 vs 11 +/- 5), age, highest heart rate (109 +/- 24 vs 120 +/- 43), and splenic AIS were not predictive of the need for an operation. Abdominal complications were lower in the AE group compared to the CT+OR (13% vs 29%), but mortality was not different (8% vs 4%). Total costs were similar for both groups after adjustment for ISS, GCS, pH, pretreatment transfusions, and spleen AIS (AE, $49,300 +/- $40,460 vs CT+OR, $54,590 +/- $34,760). The non-operative failure rate in this study was 2%. CONCLUSIONS: AE of splenic injuries is safe and associated with fewer complications. The spleen AIS, heart rate, age, and GCS did not correlate with the need for an operation. Higher ISS, lower blood pressure, lower pH, and increased number of packed red blood cell transfusions were better indicators of the need for an operation versus embolization.

Adult↗

PubMed2004

Extracorporeal life support for severe acute respiratory distress syndrome in adults.

OBJECTIVE: Severe acute respiratory distress syndrome (ARDS) is associated with a high level of mortality. Extracorporeal life support (ECLS) during severe ARDS maintains oxygen and carbon dioxide gas exchange while providing an optimal environment for recovery of pulmonary function. Since 1989, we have used a protocol-driven algorithm for treatment of severe ARDS, which includes the use of ECLS when standard therapy fails. The objective of this study was to evaluate our experience with ECLS in adult patients with severe ARDS with respect to mortality and morbidity. METHODS: We reviewed our complete experience with ELCS in adults from January 1, 1989, through December 31, 2003. Severe ARDS was defined as acute onset pulmonary failure, with bilateral infiltrates on chest x-ray, and PaO2/fraction of inspired oxygen (FiO2) ratio < or =100 or A-aDO2 >600 mm Hg despite maximal ventilator settings. The indication for ECLS was acute severe ARDS unresponsive to optimal conventional treatment. The technique of ECLS included veno-venous or veno-arterial vascular access, lung "rest" at low FiO2 and inspiratory pressure, minimal anticoagulation, and optimization of systemic oxygen delivery. RESULTS: During the study period, ECLS was used for 405 adult patients age 17 or older. Of these 405 patients, 255 were placed on ECLS for severe ARDS refractory to all other treatment. Sixty-seven percent were weaned off ECLS, and 52% survived to hospital discharge. Multivariate logistic regression analysis identified the following pre-ELCS variables as significant independent predictors of survival: (1) age (P = 0.01); (2) gender (P = 0.048); (3) pH < or =7.10 (P = 0.01); (4) PaO2/FiO2 ratio (P = 0.03); and (5) days of mechanical ventilation (P < 0.001). None of the patients who survived required permanent mechanical ventilation or supplemental oxygen therapy. CONCLUSION: Extracorporeal life support for severe ARDS in adults is a successful therapeutic option in those patients who do not respond to conventional mechanical ventilator strategies.

Adolescent↗

PubMed2004

Delayed repair for blunt thoracic aortic injury: is it really equivalent to early repair?

BACKGROUND: Blunt thoracic aortic injury (BTAI) is a severe injury that traditionally has mandated immediate surgical repair. Delaying operative intervention for BTAI can allow other life-threatening injuries to be managed first, but potentially increases the risk of aortic rupture and death. The objective of this study was to evaluate the outcome of delayed repair (DR) compared with early repair (ER) for BTAI and to assess the effectiveness of a protocol for medical control of systolic blood pressure and heart rate in those patients whose repairs were delayed. METHODS: This study is a retrospective review of University of Michigan Health System (UMHS) data from January 1, 1992, through March 1, 2003. ER was defined as operative repair within 16 hours from the time of injury. A similar analysis was conducted for patients with BTAI selected from the National Trauma Data Bank. RESULTS: For the UMHS data, there were 45 patients in the DR group and 33 patients in the ER group. Mortality in the ER group versus the DR group was 9% versus 20%. Multivariate analysis adjusting for age, Injury Severity Score, abdominal Abbreviated Injury Scale score, Glasgow Coma Scale score, and intubation status demonstrated an odds ratio for death from ER compared with DR of 1.72 (p = 0.57). Patients undergoing DR had an absolute increase in hospital length of stay (33.1 vs. 20.9 days) and complication rate (2.1 vs. 1.5 incidents per patient). A similar result was obtained for multivariate analysis of the National Trauma Data Bank data, with an odds ratio of 1.40 (p = 0.51) for death from ER versus DR. UMHS patients whose repairs were delayed achieved target systolic blood pressure and heart rate for 76% and 74% of the hourly measurements recorded, respectively. CONCLUSION: Patients with BTAI can safely undergo delayed aortic repair if other injuries warrant a higher treatment priority without increasing their overall risk of mortality. Delayed repair is, however, associated with a higher complication rate.

Adult↗

PubMed2004

Beta-blocker use is associated with improved outcomes in adult burn patients.

BACKGROUND: There is no direct evidence that beta-blockers improve mortality in burn victims. Beta-blockers attenuate hypermetabolic states in burned children, and perioperative use in elective adult cases has beneficial effects, which suggests that beta-blockers may also improve burn outcomes. However, beta-blockers decrease cardiac output and may decrease oxygen delivery, and theoretically may increase mortality. What is the effect of beta-blockers on healing time and mortality in burn patients? METHODS: This was a retrospective cohort study. We identified three cohorts of adult burn patients between 1996 and 2001: all who were on beta-blockers (BB) before their injury (PMH BB); all who were initiated on BB during their hospitalization for management of hypertension or tachyarrhythmia (HOSP BB); and control, who were never treated with beta-blockers. For each patient in the PMH BB and HOSP BB groups, two patients were placed in the control cohort by matching age and total body surface area burn. Premorbid conditions such as diabetes, hypertension, cardiac disease, renal insufficiency, and diuretic and calcium channel blocker use were analyzed. Multivariate regression models were used to identify independent modifiers. RESULTS: There were 21 PMH BB, 22 HOSP BB, and 86 control patients. All PMH BB patients remained on their BB regimen in the hospital. HOSP BB patients were initiated on beta-blockers at a mean of 8.8 days postinjury. There were no differences in age (mean, 58 +/- 17 years), total body surface area burned (mean, 14 +/- 12%), or mechanism of injury among the cohorts. The mortality rate was 5% for the PMH BB cohort, 27% for the HOSP BB cohort, and 13% for controls. The mean healing times were 51 +/- 29 days for PMH BB patients, 79 +/- 54 days for HOSP BB patients, and 60 +/- 39 for controls. In multivariate analyses, PMH BB was associated with a significant decrease in fatal outcome and healing time (p < or = 0.05 compared with control). CONCLUSION: Beta-blockers have the potential to improve adult burn outcomes. Postinjury treatment should be studied in a randomized, clinical trial.

Adrenergic beta-Antagonists↗

PubMed2004

A comparison of prehospital and hospital data in trauma patients.

OBJECTIVE: The use of prehospital data as an indicator for trauma team activation has been established. The relationship between field (Fd) and emergency department (ED) systolic blood pressure (SBP), Glasgow Coma Scale (GCS) score, and airway control as it relates to outcomes is unclear. We hypothesized that ED and Fd physiologic parameters are equally valid predictors of outcomes. In addition, we hypothesized that early field intubation will improve survival compared with later ED intubation. METHODS: Trauma registry data from two academic Level I centers from 1994 to 2001, excluding all transfers and burn patients, were analyzed using Wilcoxon signed-rank test and multivariate logistic regression with appropriate adjustments. RESULTS: There were 19,409 patients, 16,277 blunt and 3,132 penetrating trauma. There were 3,571 Fd and 746 ED intubations. ED intubation was associated with increased risk of fatal outcome compared with nonintubated patient (adjusted odds ratio, 3.1; p < 0.0001) and field intubations (adjusted odds ratio, 3.0; p < 0.0001). ED-GCS score was not significantly different from Fd-GCS score, with 82% having the same GCS category. This was not the case for SBP, and only in 60% of the cases were ED-SBP and Fd-SBP in the same category. In 31% of the patients, the ED-SBP increased, and in 9% of cases, the ED-SBP decreased compared with Fd-SBP. This was true for both blunt and penetrating trauma. Both Fd-SBP and ED-SBP were independent predicators of fatal outcome, and mortality rate significantly increased if ED-SBP category decreased compared with Fd-SBP. CONCLUSION: Early field intubation was associated with a decreased risk of fatal outcome compared with ED intubation. ED-GCS score was not significantly different from Fd-GCS score, and either one can be used to predict fatal outcome. However, ED-SBP was different from Fd-SBP in 40% of the patients, with the majority of cases having higher ED-SBP. Although ED-SBP was a better predictor of outcome, the best model is achieved when both ED and field SBP are used.

Adult↗

PubMed2003

Does bronchoalveolar lavage enhance our ability to treat ventilator-associated pneumonia in a trauma-burn intensive care unit?

BACKGROUND: Recent literature supports the notion that bronchoalveolar lavage (BAL) in ventilated trauma patients may improve our ability to diagnose and treat ventilator-associated pneumonia (VAP). We hypothesized that BAL would decrease the number of cases of VAP diagnosed and impact our antibiotic use and ventilator days. METHODS: Prospective data on all infectious complications were collected for patients admitted to the trauma-burn service for the year 2001. All VAPs between January 1, 2001, through June 30, 2001, were diagnosed without BAL (No BAL group) using clinical signs of fever, sputum production, leukocytosis, chest radiographs, and sputum culture. After July 1, 2001, VAP was diagnosed with the use of BAL. RESULTS: There were 37 cases of VAP in the No BAL group (11%) and 29 cases of VAP (8%) in the BAL group. There were no statistical differences in Injury Severity Score, hospital length of stay, ventilator days, or mortality between the two groups. The time to initial treatment of VAP was shorter for the BAL group, but did not reach significance. The number of patients who had their VAP pathogens correctly treated with empiric antibiotics was also the same between the two groups. There was no difference in the rate of recurrent pneumonias. The antibiotic costs and respiratory therapy/ventilator costs were not statistically different between the groups for trauma patients, although antibiotic costs were higher for burn patients. CONCLUSION: The routine use of BAL to diagnose VAP in our mixed trauma-burn population did not impact on clinical outcomes or antibiotic use. Our results do not justify the additional costs and potential risks of BAL for all patients. The means of VAP diagnosis may not be as important as choosing the appropriate antibiotics for common VAP organisms in any given intensive care unit.

Adult↗

PubMed2003

The cushion effect.

BACKGROUND: The pattern and severity of crash injury depends on a complex interaction of biomechanical factors such as deceleration velocity at impact (delta-V), seat-belt and airbag use, and type of impact. Human body characteristics such as height and weight may play an important role. We hypothesized that body mass index (BMI) will influence crash injury patterns. METHODS: The University of Michigan Program for Injury Research and Education database was queried. Three cohorts were analyzed, lean (BMI </= 25 kg/m2), overweight (BMI 25-30 kg/m2), and obese (BMI > 30 kg/m2) RESULTS: There were 189 detailed crash cases, with 22 fatalities. There was an increased risk of fatal outcome associated with the obese cohort (adjusted odds ratio, 4.2 compared with lean; p = 0.04). Age, delta-V, seat-belt use, and type of impact were independent predictors of Injury Severity Score (ISS). After adjusting for other modifiers, being overweight was associated with decreased ISS (p = 0.03) and abdominal maximal Abbreviated Injury Scale (mAIS) score (p = 0.008) when compared with the lean cohort. However, the lower extremity mAIS score increased when overweight (p = 0.03) and obese cohorts (p = 0.001) were compared with the lean cohort. CONCLUSION: Although no difference in ISS was identified between the lean and obese cohorts, there was an increase in mortality with the obese cohort. The severity of lower extremity injuries increased with increasing BMI. The overweight cohort was associated with lower ISS and abdominal mAIS score compared with the lean cohort. This protection may be attributable to an increase in insulating tissue, or a "cushion effect," without a significant increase in mass and momentum.

Accidents, Traffic↗

PubMedDate not supplied

Perfusion induced hyperthermia for oncologic therapy with cardiac and cerebral protection.

Cancer can be preferentially damaged and killed at temperatures above 41.0 degrees C. However, the heart and brain malfunction at this temperature, limiting the application of systemic hyperthermia in the treatment of metastatic cancer. We created a hyperthermic perfusion system that maximizes the temperature differential produced and extends the safe hyperthermic time. Mongrel dogs were anesthetized and mechanically ventilated. Temperature probes were placed in the rectum, bladder, peritoneal cavity, proximal aorta, pulmonary artery, and right tympanic canal. Venoarterial perfusion was instituted and the perfusate was warmed to 44 to 45 degrees C. The dogs' rectal temperature was elevated to > or = 42 degrees C for 4 hours. A small amount of venous blood was cooled to 28 to 30 degrees C and reperfused into the right atrium to maintain the pulmonary artery temperature < or = 38 degrees C. At the end of the perfusion, the dogs were decannulated, recovered, and returned to their cages for observation. Ten of 11 dogs survived the operative procedure, and no neurologic deficits were observed. The rectal temperature was successfully elevated to > or = 42 degrees C for 4 hours while maintaining the heart and brain at < or = 38 degrees C. Moderate serum biochemical changes were observed postprocedure. However, only the aspartate transaminase and alkaline phosphatase levels remained elevated above both the baseline and canine reference values by day 7. Lower abdominal and pelvic hyperthermia at 42 degrees C can be safely produced and maintained for 4 hours using an extracorporeal perfusion circuit, while protecting the heart and brain from temperature elevation.

Animals↗

PubMedDate not supplied

A review of 100 patients transported on extracorporeal life support.

Between May 1990 and January 1999, 100 patients (68 adult, 32 pediatric) with severe respiratory or cardiac instability were successfully transported to the University of Michigan Medical Center on extracorporeal life support. Diagnoses included adult respiratory distress syndrome (n = 78), cardiac failure (n = 7), sepsis (n = 7), asthma (n = 5), respiratory distress syndrome (of newborn) (n = 2), and airway compromise (n = 1). Of the patients, 53 were supported with venovenous bypass and 47 with venoarterial bypass. Patients were transported by ground ambulance (n = 80), helicopter (n = 15), or fixed-wing aircraft (n = 5). The median transport distance was 44 miles (range 2-790 miles), and the median transport time was 5 hours and 30 minutes (range: 1 h 33 min to 16 h 6 min). Sixty-six patients (66%) survived to discharge. One death occurred during cannulation, and two patients died before cannulation began. Complications that occurred during transport included 10 cases of electrical failure, 3 cases of circuit tubing leakage, and 1 case each of circuit rupture, membrane lung thrombosis, and membrane lung leakage. None of the complications occurring during transport had an adverse effect on outcome. We conclude that the long distance transport of patients on extracorporeal life support can be safely accomplished and is an effective option for the unstable patient with severe respiratory or cardiac failure.

Adult↗

PubMedDate not supplied

Bronchoalveolar lavage in diagnosis of ventilator-associated pneumonia in patients with burns.

Ventilator-associated pneumonia (VAP) remains a major cause of morbidity and mortality for patients with burns. In nonburn populations, bronchoalveolar lavage (BAL) excludes other pathology such as systemic inflammatory response syndrome. We hypothesized that BAL would decrease our false-positive VAP rate. All ventilated patients with burn injury who were admitted to our institution from July 2000 through June 2003 were included. After June 2001, BAL was used to make the diagnosis of VAP, with > or =10(4) organisms considered a positive result. Fifty patients met criteria for VAP, 21 in the pre-BAL period and 29 in the BAL period. Six patients (21%) in the BAL group had quantitative cultures <10(4) and were not treated. The outcomes for these patients were not different than those treated for VAP. There were no differences in age, TBSA size, antibiotic use, or ventilator days for the pre-BAL or BAL groups, although the pneumonia rate was lower for the BAL time period. The use of BAL eliminated the unnecessary antibiotic treatment of 21% of patients in the BAL time period and was associated with a lower rate of VAP.

Adolescent↗