The military gear microbiome: risk factors surrounding the warfighter.

Combat extremity wounds are highly susceptible to contamination from surrounding environmental material. This bioburden could be partially transferred from materials in immediate proximity to the wound, including fragments of the uniform and gear. However, the assessment of the microbial bioburden present on military gear during operational conditions of deployment or training is relatively unexplored. Opportunistic pathogens that can survive on gear represent risk factors for infection following injury, especially following combat blasts, where fibers and other materials are embedded in wounded tissue. We utilized 16S rRNA sequencing to assess the microbiome composition of different military gear types (boot, trouser, coat, and canteen) from two operational environments (training in Hawai'i and deployed in Indonesia) across time (days 0 and 14). We found that microbiome diversity, stability, and composition were dependent on gear type, training location, and sampling timepoint. At day 14, species diversity was significantly higher in Hawai'i samples compared to Indonesia samples for boot, coat, and trouser swabs. In addition, we observed the presence of potential microbial risk factors, as opportunistic pathogenic species, such as Acinetobacter, Pseudomonas, and Staphylococcus, were found to be present in all sample types and in both study sites. These study outcomes will be used to guide the design of antimicrobial materials and uniforms and for infection control efforts following combat blasts and other injuries, thereby improving treatment guidance during military training and deployment.IMPORTANCECombat extremity wounds are vulnerable to contamination from environments of proximity to the warfighter, leading to potential detrimental outcomes such as infection and delayed wound healing. Therefore, microbial surveillance of such environments is necessary to aid the advancement of military safety and preparedness through clinical diagnostics, treatment protocols, and uniform material design.

Assessing the use of a micro-sampling device for measuring blood protein levels in healthy subjects and COVID-19 patients.

BACKGROUND: Venous phlebotomy performed by trained personnel is critical for patient diagnosis and monitoring of chronic disease, but has limitations in resource-constrained settings, and represents an infection control challenge during outbreaks. Self-collection devices have the potential to shift phlebotomy closer to the point of care, supporting telemedicine strategies and virtual clinical trials. Here we assess a capillary blood micro-sampling device, the Tasso Serum Separator Tube (SST), for measuring blood protein levels in healthy subjects and non-hospitalized COVID-19 patients. METHODS: 57 healthy controls and 56 participants with mild/moderate COVID-19 were recruited at two U.S. military healthcare facilities. Healthy controls donated Tasso SST capillary serum, venous plasma and venous serum samples at multiple time points, while COVID-19 patients donated a single Tasso SST serum sample at enrolment. Concentrations of 17 protein inflammatory biomarkers were measured in all biospecimens by Ella multi-analyte immune-assay. RESULTS: Tasso SST serum protein measurements in healthy control subjects were highly reproducible, but their agreements with matched venous samples varied. Most of the selected proteins, including CRP, Ferritin, IL-6 and PCT, were well-correlated between Tasso SST and venous serum with little sample type bias, but concentrations of D-dimer, IL-1B and IL-1Ra were not. Self-collection at home with delayed sample processing was associated with significant concentrations differences for several analytes compared to supervised, in-clinic collection with rapid processing. Finally, Tasso SST serum protein concentrations were significantly elevated in in non-hospitalized COVID-19 patients compared with healthy controls. CONCLUSIONS: Self-collection of capillary blood with micro-sampling devices provides an attractive alternative to routine phlebotomy. However, concentrations of certain analytes may differ significantly from those in venous samples, and factors including user proficiency, temperature control and time lags between specimen collection and processing need to be considered for their effect on sample quality and reproducibility.

ECMO with vasopressor use during early endotoxic shock: Can it improve circulatory support and regional microcirculatory blood flow?

INTRODUCTION: While extracorporeal membrane oxygenation (ECMO) is effective in preventing further hypoxemia and maintains blood flow in endotoxin-induced shock, ECMO alone does not reverse the hypotension. In this study, we tested whether concurrent vasopressor use with ECMO would provide increased circulatory support and blood flow, and characterized regional blood flow distribution to vital organs. METHODS: Endotoxic shock was induced in piglets to achieve a 30% decrease in mean arterial pressure (MAP). Measurements of untreated pigs were compared to pigs treated with ECMO alone or ECMO and vasopressors. RESULTS: ECMO provided cardiac support during vasodilatory endotoxic shock and improved oxygen delivery, but vasopressor therapy was required to return MAP to normotensive levels. Increased blood pressure with vasopressors did not alter oxygen consumption or extraction compared to ECMO alone. Regional microcirculatory blood flow (RBF) to the brain, kidney, and liver were maintained or increased during ECMO with and without vasopressors. CONCLUSION: ECMO support and concurrent vasopressor use improve regional blood flow and oxygen delivery even in the absence of full blood pressure restoration. Vasopressor-induced selective distribution of blood flow to vital organs is retained when vasopressors are administered with ECMO.

ECMO Maintains Cerebral Blood Flow During Endotoxic Shock in Piglets.

Cerebrovascular injury while on extracorporeal membrane oxygenation (ECMO) may be caused by excessive brain perfusion during hypoxemic reperfusion. Previous studies have postulated that the most vulnerable period of time for cerebrovascular injury is during the transfer period to ECMO. Therefore, our objective was to compare brain perfusion and hemodynamics in a piglet endotoxic shock ECMO model. The effect of ECMO flow on microcirculation of different brain regions was compared between 10 control pigs and six pigs (7-10 kg) administered IV endotoxin to achieve a drop in mean arterial blood pressure (MAP) of at least 30%. Cardiac output (CO), brain oxygen utilization, and microcirculatory blood flow (BF) were compared at baseline and 2 hours after ECMO stabilization. Matching ECMO delivery with baseline CO in control animals increased perfusion (p < 0.05) in all areas of the brain. In contrast, with endotoxin, ECMO returned perfusion closer to baseline levels in all regions of the brain and maintained brain tissue oxygen consumption. Both control and endotoxic pigs showed no evidence of acute neuronal necrosis in histologic cerebral cortical sections examined after 2 hours of ECMO. Results show that during endotoxic shock, transition to ECMO can maintain brain BF equally to all brain regions without causing overperfusion, and does not appear to cause brain tissue histopathologic changes (hemorrhage or necrosis) during the acute stabilization period after ECMO induction.

Simultaneous Extraction of Viral and Bacterial Nucleic Acids for Molecular Diagnostic Applications.

Molecular detection of microbial pathogens in clinical samples requires the application of efficient sample lysis protocols and subsequent extraction and isolation of their nucleic acids. Here, we describe a simple and time-efficient method for simultaneous extraction of genomic DNA from gram-positive and -negative bacteria, as well as RNA from viral agents present in a sample. This method compared well with existing bacterial- and viral-specialized extraction protocols, worked reliably on clinical samples, and was not pathogen specific. This method may be used to extract DNA and RNA concurrently from viral and bacterial pathogens present in a sample and effectively detect coinfections in routine clinical diagnostics.

Vasopressin decreases pulmonary-to-systemic vascular resistance ratio in a porcine model of severe hemorrhagic shock.

Vasopressors are gaining renewed interest as treatment adjuncts in hemorrhagic shock. The ideal vasoconstrictor will increase systemic blood pressure without increasing pulmonary vascular resistance (PVR), which hinders pulmonary perfusion and exacerbates hypoxemia. However, the selectivity of pressors for pulmonary versus systemic vasoconstriction during hemorrhage has not been characterized. The purpose of this study was to test the hypothesis that vasopressin (VP) has distinct effects on pulmonary versus systemic hemodynamics, unlike the catecholamine vasopressors norepinephrine (NE) and phenylephrine (PE). Anesthetized and ventilated pigs were assigned to resuscitation with saline only (n = 7) or saline with VP (n = 6), NE (n = 6), or PE (n = 6). Animals were hemorrhaged to a target volume of 30 mL/kg and a mean arterial pressure of 35 mmHg. One hour after the start of hemorrhage, animals were resuscitated with saline up to one shed blood volume, followed by either additional saline or a vasopressor. Hemodynamics and oxygenation were measured hourly for 4 h after the start of hemorrhage. Vasopressin increased systemic vascular resistance (SVR) while sparing the pulmonary vasculature, leading to a 45% decrease in the PVR/SVR ratio compared with treatment with PE. Conversely, NE induced pulmonary hypertension and led to an increased PVR/SVR ratio associated with decreased oxygen saturation. Phenylephrine and crystalloid had no significant effect on the PVR/SVR ratio. Sparing of pulmonary vasoconstriction occurs only with VP, not with administration of crystalloid or catecholamine pressors. The ability of VP to maintain blood oxygenation indicates that VP may prevent hypoxemia in the management of hemorrhagic shock.

Is arginine/asymetric dimethylarginine ratio depletion an indicator of insufficient resuscitation in a porcine model of hemorrhage-reperfusion?

BACKGROUND: Hemorrhagic shock leads to a complex cascade of metabolic and hormonal processes that may result in hypoperfusion, end organ damage, and death even when blood pressure is restored. Studies have shown that morbidity and mortality could be attributable to a diminished availability of endothelial-derived nitric oxide (eNO). It is unclear whether adequate levels of citrulline (CIT) and arginine (ARG)--the precursors of eNO synthesis--are available to sustain the eNO needed to maintain adequate perfusion in severe shock. An indirect measure of eNO is the ratio between the levels of ARG and its inhibitor asymmetric dimethylarginine (ARG/ADMA). The purpose of the study was to identify the temporal impact of the ARG/ADMA ratio, ARG, CIT, and ADMA in response to hemorrhage and crystalloid fluid resuscitation by the use of a porcine model of severe hemorrhagic shock. METHODS: Hemorrhagic shock was induced in Yorkshire cross pigs by mimicking a bleeding pattern of rapid uncontrolled hemorrhage to achieve a shed volume of 30 mL/kg, a 50% decrease in mean arterial pressure, and an oxygen debt of >60 mL/kg. Normal saline, up to 2 times the shed blood volume, was started 1 hour after the start of hemorrhage with the goal of restoring mean arterial pressure to >50 mm Hg. Hemodynamics, blood gas measurements, and plasma samples were obtained at baseline, 1 hour after the start of hemorrhage, and 1 hour after resuscitation. Amino acids were measured by liquid chromatography coupled to mass spectrometry. RESULTS: During hemorrhage, a distinct subset of pigs was better able to tolerate ischemia than the rest. These pigs required less resuscitation, had evidence of better organ perfusion, and exhibited less of an increase in interleukin-6 (IL-6) after resuscitation. Compared with their less-tolerant counterparts, this group had a greater increase in CIT above baseline (analysis of variance, P < .05) with hemorrhage. ARG levels were similar and remained stable with hemorrhage, which indicated the similar availability of substrate for eNO synthesis but differences in the quantity produced in response to the blood volume loss. With crystalloid fluid resuscitation, ARG levels and ARG/ADMA decreased (analysis of variance, P < .05), whereas CIT remained increased in the group less able to tolerate hemorrhage. ARG/ADMA decreased proportional to greater oxygen debt during hemorrhage and greater IL-6 levels with fluid resuscitation. CONCLUSION: Our results suggest that a sufficient decrease in MAP during hemorrhagic shock is associated with a subsequent increase in IL-6, persisting impairment of end organ perfusion, and evidence of ongoing eNO deficit and an increase in ADMA despite resuscitation. The ARG/ADMA ratio reflects both of these parameters and corresponds to the increase in IL-6 and persistent ischemia after resuscitation. We propose that the mechanism of IL-6 increase in trauma derives from eNO deficiency, and the ARG/ADMA ratio more accurately depicts the pathologic mechanism responsible for increased morbidity and mortality in trauma.

Role of vasopressin in maintenance of potassium homeostasis in severe hemorrhage.

Uncontrolled elevation in plasma potassium within minutes of rapid blood volume loss is associated with mortality and distinguishes nonsurvivors of severe hemorrhage from survivors. In a pig model of severe hemorrhage, we discovered that along with a sharp increase in plasma potassium coincident with a shut down of urine flow, nonsurvivors also had an insufficient vasopressin response to hemorrhage. In contrast, survivors did have elevated vasopressin levels in response to hemorrhage and maintained plasma potassium within normal limits. While it has been demonstrated for some time that vasopressin can influence secretion of potassium in the distal nephron, the magnitude of this effect and conditions under which this contributes to physiological modulation of potassium excretion has yet to be defined. In this review, we assess the evidence that would suggest that vasopressin plays a key role in modulating potassium excretion and is important in the regulation of potassium homeostasis during hemorrhage.

Continuous renal replacement therapy to reduce inflammation in a piglet hemorrhage-reperfusion extracorporeal membrane oxygenation model.

BACKGROUND: During extracorporeal membrane oxygenation (ECMO), circulation of blood across synthetic surfaces triggers an inflammatory response. Therefore, we evaluated the ability of continuous renal replacement therapy (CRRT) to remove cytokines and reduce the inflammatory response in a piglet hemorrhage-reperfusion ECMO model. METHODS: Three groups were studied: (i) uninjured controls (n = 11); (ii) hemorrhage-reperfusion while on venoarterial ECMO (30% hemorrhage with subsequent blood volume replacement within 60 min) (n = 8); (iii) treatment with CRRT after hemorrhage-reperfusion while on ECMO (n = 7). Hemodynamic parameters, oxygen utilization, and plasma and broncho-alveolar lavage (BAL) cytokine levels were recorded and lung tissue samples collected for histologic comparison. RESULTS: Whereas mean arterial pressures decreased among hemorrhage-reperfusion piglets, ECMO with CRRT did not significantly alter mean arterial pressures or systemic vascular resistance and was able to maintain blood flow as well as oxygen delivery after hemorrhage-reperfusion. Plasma interleukin (IL)-6 and IL-10, and BAL tumor necrosis factor (TNF)-α, IL-1ß, IL-6, IL-8, and IL-10 increased as a result of hemorrhage-reperfusion while on ECMO. After a 6-h period of CRRT, plasma IL-6 and BAL TNF-α, IL-6, and IL-8 levels decreased. CONCLUSION: Data suggest CRRT may decrease inflammatory cytokine levels during the initial phase of ECMO therapy following hemorrhage-reperfusion while maintaining cardiac output and oxygen utilization.

Effects of hyperglycemia and continuous intravenous insulin on outcomes of surgical patients.

BACKGROUND: Hyperglycemia in critically ill patients has been associated with increased morbidity and mortality. It is unclear to what degree hyperglycemia should be regulated in a mixed surgical population. STUDY DESIGN: A retrospective chart review of 210 surgical patients in the intensive care unit (ICU) was performed. All patients were placed on an intravenous insulin protocol targeted to a blood glucose (BG) of 80-140 mg/dL. Outcomes were compared between surgical patients with controlled BG levels (80-140 mg/dL) versus uncontrolled levels (>140 mg/dL). RESULTS: The mortality rate of this population was 12%, 5% in the controlled BG group compared with 18% in the uncontrolled BG group (P < 0.01). After adjusting for covariates, the mortality rate of the uncontrolled blood glucose group was significantly greater (OR = 4.8, 95% CI 1.4-20; P = 0.02). The overall hypoglycemic rate was <1%, and was not associated with a higher mortality, P = 0.60. A greater mortality rate was associated with patients who spent a greater time with blood glucose values >181 mg/dL (OR = 1.3, 95% CI 1.1-1.6; P = 0.01). CONCLUSIONS: Increased mortality was associated with surgical patients in the uncontrolled blood glucose group compared with patients who were well controlled with insulin therapy. These results are comparable to previous studies and indicate that surgical patients are a population who may benefit from tighter glycemic control. Further investigations through prospective randomized studies are needed to fully evaluate the effects of hyperglycemia in a diverse surgical population as well as specific surgical subspecialties.

Effects of combination dobutamine and vasopressin therapy on microcirculatory blood flow in a porcine model of severe endotoxic shock.

BACKGROUND: Dobutamine (DB) has been recommended in combination with vasopressor therapy in septic shock, given its reported ability to improve mesenteric and microcirculatory perfusion. Vasopressin (VP) is typically reserved as a second-line agent due to the concern of ischemia. The purpose of our study was to determine whether combination DB and VP therapy improved microcirculatory blood flow in severe endotoxic shock. METHODS: Septic shock was induced in 20 anesthetized piglets with injection of E. coli endotoxin. DB (10 µg/kg/min, n = 5) and VP (0.04 units/min, n = 10) were administered alone and in combination (n = 15). Measurements were compared at baseline, following endotoxin administration, and following treatment. Microcirculatory blood flow was determined via the injection of colored microspheres. RESULTS: VP completely reversed endotoxin-mediated hypotension with a mean arterial pressure (MAP) of 85 ± 4.5 mm Hg, which was not significantly altered with the addition of DB (77 ± 4.9 mm Hg). Endotoxin uniformly depressed cardiac output (CO) from baseline (227 ± 10.7 versus 174 ± 12.4 mL/min/kg) despite treatment with VP alone or in combination with DB. The addition of DB did not improve the CO in this severe septic shock model. VP was found to shunt microcirculatory flow from the skin and GI tract to vital organs such as the brain, liver, and kidneys, which was not altered with the addition of DB. CONCLUSIONS: Results indicate that DB is ineffective in increasing CO or improving mesenteric blood flow when used with physiologic replacement doses of VP. In combination, DB is unable to overcome the blood flow distribution achieved with VP administration alone in severe endotoxic shock.

Deficiency in Six2 during prenatal development is associated with reduced nephron number, chronic renal failure, and hypertension in Br/+ adult mice.

The Br/+ mutant mouse displays decreased embryological expression of the homeobox transcription factor Six2, resulting in hertitable renal hypoplasia. The purpose of this study was to characterize the renal physiological consequences of embryonic haploinsuffiency of Six2 by analyzing renal morphology and function in the adult Br heterozygous mutant. Adult Br/+ kidneys weighed 50% less than those from wild-type mice and displayed glomerulopathy. Stereological analysis of renal glomeruli showed that Br/+ kidneys had an average of 88% fewer glomeruli than +/+ kidneys, whereas individual glomeruli in Br/+ mice maintained an average volume increase of 180% compared with normal nephrons. Immunostaining revealed increased levels of endothelin-1 (ET-1), endothelin receptors A (ET(A)) and B (ET(B)), and Na-K-ATPase were present in the dilated renal tubules of mutant mice. Physiological features of chronic renal failure (CRF) including elevated mean arterial pressure, increased plasma creatinine, and dilute urine excretion were measured in Br/+ mutant mice. Electron microscopy of the Br/+ glomeruli revealed pathological alterations such as hypercellularity, extracellular matrix accumulation, and a thick irregular glomerular basement membrane. These results indicate that adult Br/+ mice suffer from CRF associated with reduced nephron number and renal hypoplasia, as well as glomerulopathy. Defects are associated with embryological deficiencies of Six2, suggesting that proper levels of this protein during nephrogenesis are critical for normal glomerular development and adult renal function.

The utility of serum leptin and follicular fluid leptin, estradiol, and progesterone levels during an in vitro fertilization cycle.

PURPOSE: To prospectively evaluate serum and follicular fluid leptin, estradiol, and progesterone levels during in vitro fertilization. METHODS: Prospective observational study measuring serum levels at six points during the IVF cycle and follicular fluid at the time of retrieval. RESULTS: Serum leptin and estradiol levels both significantly increased for the individual patients during the IVF stimulation process. None of the leptin levels differed based on pregnancy outcome. BMI significantly correlated with all leptin levels. Follicular fluid estradiol correlated with serum estradiol only in pregnant patients (r = 0.97, p<0.01) and was unrelated in non-pregnant patients (r=-0.15, p=0.81). CONCLUSION: Serum and follicular leptin levels are highly correlated. Leptin levels increase during the IVF cycle and vary between patients based on maternal BMI, but do not correlate with other serum hormone levels or pregnancy outcome. Pregnancy outcome success was reflected in the relationship between follicular fluid and serum levels of estradiol, independent of leptin levels.

Physiological changes in venous hemodynamics associated with elective fasciotomy.

It has been postulated that lower extremity fasciotomy may disrupt the calf musculovenous pump and predisposes to development of chronic venous insufficiency (CVI). However, studies based on trauma patients who undergo emergent fasciotomy are confounded by the possibility of concomitant vascular and soft tissue injury and use historical controls. This is a prospective study that evaluates venous hemodynamics in young patients undergoing elective fasciotomy for chronic exertional compartment syndrome (CECS), eliminating the problems associated with retrospective study of trauma patients. CECS was diagnosed by history and, when indicated, measurement of compartment pressures. Prior to elective two- or four-compartment fasciotomy, each patient underwent lower extremity air plethysmography (APG) and colorflow duplex ultrasonography. These studies were repeated a minimum of 6 weeks postoperatively. Fifteen patients who had fasciotomies for CECS were studied; two of these patients had bilateral fasciotomies for a total of 17 limbs. There were 13 male and two female patients (average age 31.2 years). APG and colorflow duplex were performed an average of 12 weeks after fasciotomy. Outflow fraction, venous volume, and ejection volume showed no significant changes postoperatively. However, the venous filling index (VFI) increased (0.9 +/- 0.1 vs. 1.1 +/- 0.1 mL/sec; p < 0.05, paired t-test), the ejection fraction tended to decrease (59 +/- 4% vs. 52 +/- 2%; p < 0.08, paired t-test), and the residual volume fraction (RVF) increased (26 +/- 3% vs. 36 +/- 5%; p < 0.05, paired t-test). There were no patients with evidence of deep venous reflux. Two extremities with preoperative greater saphenous vein (GSV) reflux did not worsen, and three extremities developed new GSV reflux following fasciotomy, although VFI remained normal in each extremity. Elective fasciotomy for CECS does not lead to significant venous reflux but likely does diminish calf muscle pump function and increases RVF moderately in young adult patients. With longer follow-up this diminished calf muscle pump function may increase the risk of CVI.

Effects of prenatal ethanol exposure and sex on the arginine vasopressin response to hemorrhage in the rat.

AVP synthesis, storage, and osmotically stimulated release are reduced in young adult rats exposed prenatally to ethanol (PE). Whether the reduced release of AVP to the osmotic stimulus is due to impairment of the vasopressin system or specifically to an osmoreceptor-mediated release is not known. The present experiments were done, therefore, to determine whether a hemorrhage-induced AVP response would also be diminished in PE-exposed rats. Pregnant rats were fed either a control liquid diet [no prenatal ethanol (NPE)] or a liquid diet with 35% of the calories from ethanol from days 7-21 of pregnancy. Offspring were weaned at 3 wk of life. At 11 wk of age, femoral arterial catheters were surgically placed, and blood volumes were determined at 12 wk. Three days later, two hemorrhages of 10% of the blood volume were performed with samples taken before and 10 min after the hemorrhages. After a 20% blood loss, plasma AVP was 19% higher in NPE rats than in the PE rats despite no differences in mean arterial blood pressure (MABP). Also, hypothalamic AVP mRNA and pituitary AVP content were reduced in PE rats. Furthermore, confirming an earlier report of sex differences in AVP release, the hemorrhage-induced hormone response was twofold greater in female rats than male rats, regardless of previous ethanol exposure. These studies demonstrate that the AVP response to hemorrhage is reduced in PE rats independently of differences in MABP. The data are compatible with a theory of a reduced number of hemorrhage-responsive vasopressinergic neurons capable of stimulated AVP release in PE rats.

Prenatal exposure to ethanol causes partial diabetes insipidus in adult rats.

Chronic consumption of ethanol in adult rats and humans leads to reduced AVP-producing neurons, and prenatal ethanol (PE) exposure has been reported to cause changes in the morphology of AVP-producing cells in the suprachiasmatic nucleus of young rats. The present studies further characterize the effects of PE exposure on AVP in the young adult rat, its hypothalamic synthesis, pituitary storage, and osmotically stimulated release. Pregnant rats were fed a liquid diet with 35% of the calories from ethanol or a control liquid diet for days 7-22 of pregnancy. Water consumption and urine excretion rate were measured in the offspring at 60-68 days of age. Subsequently, the offspring were infused with 5% NaCl at 0.05 ml.kg(-1).min(-1) with plasma samples taken before and at three 40-min intervals during infusion for measurement of AVP and osmolality. Urine output and water intake were approximately 20% greater in PE-exposed rats than in rats with no PE exposure, and female rats had a greater water intake than males. The relationship between plasma osmolality and AVP in PE-exposed rats was parallel to, but shifted to the right of, the control rats, indicating an increase in osmotic threshold for AVP release. Pituitary AVP was reduced by 13% and hypothalamic AVP mRNA content was reduced by 35% in PE-exposed rats. Our data suggest that PE exposure can cause a permanent condition of a mild partial central diabetes insipidus.

Matrix metalloproteinases in patients with myocardial infarction and percutaneous revascularization.

BACKGROUND: Extracellular matrix remodeling is a component of coronary artery disease (CAD). Matrix metalloproteinases (MMPs) are enzymes involved in extracellular matrix degradation. The extrapolation of the role MMPs play in the clinical setting of acute coronary syndromes has not yet been defined. METHODS: Samples from 100 subjects undergoing cardiac catheterization were analyzed for serum levels of MMP-1, MMP-2, and MMP-9. These markers were assessed before, immediately after, and 24 hours after cardiac catheterization. Relationships among MMP levels, baseline characteristics, angiography findings and clinical course were assessed. RESULTS: Comparing subjects with myocardial infarction versus those without, baseline MMP-1 levels were not different at baseline but increased during the hospital stay, MMP-2 levels were higher at baseline and throughout the monitoring period and MMP-9 levels lower and decreased over time. MMP-1 was higher 24 hours after catheterization in subjects undergoing revascularization. Subjects undergoing percutaneous revascularization had higher MMP-9 levels following revascularization than those subjects undergoing angiography without angioplasty. CONCLUSIONS: Serial monitoring of MMPs indicates a differential subtype response to myocardial infarction and percutaneous revascularization. Results of this study indicate that MMP subtypes may play differing roles in the manifestation of acute coronary syndromes and response to revascularization.

Lavage administration of dilute surfactant in a piglet model of meconium aspiration.

Maldistribution of exogenous surfactant may preclude any clinical response in acute lung injury associated with surfactant dysfunction. Our previous studies have shown the effectiveness of surfactant lavage after homogenous lung injury. The present study utilizes a histologically confirmed non-homogeneous lung injury model induced by saline lung-lavage followed by meconium injected into a mainstem bronchus. Piglets were then treated with Infasurf or Exosurf by lavage (I-LAVAGE, n = 7; E-LAVAGE, n = 5) or bolus (I-BOLUS, n = 8; E-BOLUS, n = 5), or went untreated (CONTROL, n = 4). Lavage administration utilized a dilute surfactant (35 ml/kg; 4 mg phospholipid/ml) instilled into the lung, followed by gravity drainage. The retained doses of the respective surfactant in the lavage and bolus groups were similar. Results showed that the surfactant distribution was more uniform in the lavage groups compared to the bolus groups. Significant and consistent increases in PaO2 were observed in the lavage groups compared to the bolus groups and the controls. PaO2 (mmHg) at 240 min posttreatment: I-LAVAGE = 297 +/- 54, E-LAVAGE = 280 +/- 57; I-BOLUS = 139 +/- 31; E-BOLUS = 152 +/- 29; C = 119 +/- 73 (mean +/- SEM). Other improved pulmonary function parameters favored lavage administration. We conclude that better surfactant distribution achieved by lavage administration can be more effective than bolus administration in this type of non-homogeneous lung injury.

Nosocomial transmission of methicillin-resistant Staphylococcus aureus: a blinded study to establish baseline acquisition rates.

OBJECTIVE: To define the extent of nosocomial transmission of methicillin-resistant Staphylococcus aureus (MRSA) in patients admitted to a tertiary-care hospital. DESIGN: A blinded, prospective surveillance culture study of patients admitted to the hospital to determine the transmission (acquisition) rate of MRSA. Risk factors associated with the likelihood of MRSA colonization on admission were investigated. SETTING: Tertiary-care military medical facility. PARTICIPANTS: All patients admitted to the medicine, surgery, and pediatric wards, and to the medical, surgical, and pediatric intensive care units were eligible for inclusion. RESULTS: Five hundred thirty-five admission and 374 discharge samples were collected during the study period. One hundred forty-one patients were colonized with methicillin-susceptible S. aureus (MSSA) and 20 patients (3.7%) were colonized with MRSA on admission. Of the 354 susceptible patients, 6 acquired MRSA during the study for a transmission rate of 1.7%. Patients colonized with MRSA on admission were more likely to be older than non-colonized or MSSA-colonized patients, to have received antibiotics within the past year, to have been hospitalized within the prior 3 years, or to have a known history of MRSA. Patients acquiring MRSA had an average hospital stay of 17.7 days compared with 5.3 days for those who did not acquire MRSA. Pulsed-field gel electrophoresis of the 6 MRSA isolates from patients who acquired MRSA revealed 4 distinct band patterns. CONCLUSIONS: Most patients colonized with MRSA were identified on admission samples. Surveillance cultures of patients admitted may help to prevent MRSA transmission and infection.

Family member presence during cardiopulmonary resuscitation: a survey of US and international critical care professionals.

OBJECTIVE: Recent international emergency cardiovascular care (ECC) and cardiopulmonary resuscitation (CPR) guidelines have recommended that health-care professionals allow family members to be present during resuscitation attempts. To assess whether critical care professionals support these recommendations, we surveyed health-care professionals for their opinions regarding family-witnessed resuscitation (FWR). METHODS: We surveyed health-care professionals attending the International Meeting of the American College of Chest Physicians in San Francisco, CA, from October 23 to 26, 2000, about their CPR experience, their opinions on FWR, and demographic characteristics. The opinions of physicians, nurses, and other allied health professionals were compared, and differences in opinions based on demographics were examined. RESULTS: Five hundred ninety-two professionals were surveyed. Fewer physicians (20%) than nurses and allied health-care workers combined (39%) would allow family member presence during adult CPR (p = 0.0037 [chi(2) test]). Fourteen percent of physicians and 17% of nurses would allow a family presence during pediatric CPR. There was a significant difference among the opinions of US professionals, based on regional location. Professionals practicing in the northeastern states were less likely than other US professionals to allow FWR during adult or pediatric resuscitations (p = 0.016 and p < 0.001, respectively [chi(2) test]). Midwestern professionals were more likely than others to allow family members to be present during an adult resuscitation, when compared to professional in the rest of the nation (p = 0.002 [chi(2) test]). Health-care professionals disapproving of family member presence during CPR did so because of the fear of psychological trauma to family members, performance anxiety affecting the CPR team, medicolegal concerns, and a fear of distraction to the resuscitation team. CONCLUSIONS: Our evaluation indicated that the majority of critical care professionals surveyed do not support the current recommendations provided by the ECC and CPR guidelines of 2000.