Catherine F. T. Uyehara

RATES OF CARRIAGE OF METHICILLIN-RESISTANT AND METHICILLIN-SUSCEPTIBLE STAPHYLOCOCCUS AUREUS IN AN OUTPATIENT POPULATION

OBJECTIVES To assess the prevalence of and the clinical features associated with asymptomatic Staphylococcus aureus colonization in a healthy outpatient population, and to compare the characteristics of colonizing methicillin-resistant S. aureus (MRSA) strains with those of strains causing infection in our community and hospital. SETTING Outpatient military clinics. METHODS Specimens were obtained from the nares, pharynx, and axillae of 404 outpatients, and a questionnaire was administered to obtain demographic and risk factor information. MRSA strains were typed by pulsed-field gel electrophoresis (PFGE) and evaluated for antibiotic susceptibility. Antibiograms of study MRSA strains were compared with those of MRSA strains causing clinical illness during the same time period. RESULTS Methicillin-susceptible S. aureus (MSSA) colonization was present in 153 (38%) of the 404 asymptomatic outpatients, and MRSA colonization was present in 8 (2%). Detection of colonization was highest from the nares. No clinical risk factor was significantly associated with MRSA colonization; however, a tendency was noted for MRSA to be more common in men and in those who were older or who had been recently hospitalized. All colonizing MRSA strains had unique patterns on PFGE. In contrast to strains responsible for hospital infections, most colonizing isolates of MRSA were susceptible to oral antibiotics. CONCLUSIONS MRSA and MSSA colonization is common in our outpatient population. Colonization is best detected by nares cultures and most carriers of MRSA are without apparent predisposing risk factors for acquisition. Colonizing isolates of MRSA are heterogeneous and, unlike nosocomial isolates, often retain susceptibility to other non-beta-lactam antibiotics.

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.

Long-term impact of the women’s health initiative on HRT

ObjectiveTo evaluate the long-term trends in the HRT following the results of the WHI, which were made public in July 2002.Study designAn observational cohort study was performed from prescription data of estrogen containing products ordered from Tripler Army Medical Center between July 1999 and July 2005. We used automated pharmacy data to identify all estrogen products dispensed to active duty soldiers, dependent wives, and retirees during the study period. Differences in prescription rate were compared between groups using a Student’s t-test.ResultsA total of 71,592 prescriptions were written for HRT. Prescriptions decreased from 1,272/month at the start of the study to 493/month at the conclusion of the study. Prior to July 2002 OBGYNs were the first to decrease their prescribing rate of estrogen, and this decrease was greater than other specialties analyzed. The frequency of HRT prescriptions decreased after July 2002 while the percentage of patients who filled HRT prescriptions increased from 68 to 72%.ConclusionsWe have found a significant decrease in prescriptions after release of the WHI initiative results. With this decrease in prescribing rate of HRT we found that a greater percentage of women actually filled their prescriptions perhaps indicating greater certainty in their choice.

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

AbstractPurpose: 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.

Lavage administration of dilute recombinant surfactant in acute lung injury in piglets.

In an acute lung injury model, we previously observed reversal of pulmonary dysfunction with natural surfactant administered by lavage (dose = 18 mg/kg phospholipid). The present study questioned whether a lower dose of phospholipid would be effective if a recombinant preparation rather than natural surfactant were used. Acute lung injury was induced by repeated saline lung lavage in ventilated, sedated, and paralyzed piglets. Three concentrations of recombinant surfactant were studied (low phospholipid, 1 mg/mL; medium phospholipid, 4 mg/mL; high phospholipid, 13.5 mg/mL). Control piglets received no surfactant. Thirty-five milliliters per kilogram of surfactant was administered by gravity, followed by passive drainage of excess fluid. All treatment groups retained similar volumes (4.7 ± 0.3 mL/kg), corresponding to phospholipid doses of 4 ± 0.4, 22 ± 3, and 67 ± 4 mg/kg in low, medium, and high-dose groups, respectively. Treatment groups showed significant improvement in PaO2 compared with controls. Other parameters different from controls were found in only the medium and high-dose groups. All surfactant-treated groups showed improvement over time in PaO2, PaCO2, lung resistance, mean airway pressure, functional residual capacity, and dynamic compliance. These data support the statement that whereas there is a dose response to exogenous surfactant, the effective dose of recombinant surfactant in acute lung injury may be as low as 4 mg/kg phospholipid when administered by lavage.

Metabolism of Neurohypophysial Hormonesa

Over the past decade several new routes of neurohypophysial hormone metabolism have been identified. These include nonhepatic splanchnic clearance and renal clearance in addition to filtration that appears to be receptor mediated. The intraluminal degradation of VP in the proximal tubule, and distal tubular secretion, at least in one species, has been identified. The brain has been identified as a site for VP and OT metabolism, and the amniotic sac may be a major site for VP clearance in the guinea pig fetus. There have been generalized findings regarding VP and OT metabolism. First, VP metabolism in the whole body and in the amniotic sac appears to increase with increasing concentrations of hormone; this does not appear to be the case with OT. Also, evidence has been presented that suggests a potential for the formation of biologically active metabolites. There have been several associations of pathophysiological states with altered VP or OT metabolism, sometimes with plasma levels remaining unchanged. Lastly, caution is emphasized when measuring these hormones by RIA, and differences in specificities of antisera toward hormone metabolites must be considered.

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-1β, 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.

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.

Surfactant Lavage with Lidocaine Improves Pulmonary Function in Piglets after HCl-Induced Acute Lung Injury

Acute respiratory distress syndrome (ARDS) is associated with significant morbidity and mortality. The pathophysiology of ARDS includes abnormalities of surfactant function as well as pulmonary inflammation. Immunomodulating drugs, like Lidocaine, have shown some success in decreasing inflammation in ARDS. We attempted to combine surfactant lavage’s ability to reverse the surfactant dysfunction, while acting as a vehicle to deliver Lidocaine. Gravity-driven surfactant (Infasurf) lavage (35 ml/kg) was administered alone or mixed with Lidocaine after severe HCl acid injury (0.3 N; 3 cc/kg) in neonatal piglets. Treatment groups included: control (C) (n = 5), surfactant lavage (SL) (35 ml/kg-diluted Infasurf) (n = 7) and SL mixed with Lidocaine (SL+L) (n = 7). About 26–27% of the lavage was retained (phospholipid 73–74 mg/kg; Lidocaine 1.8 mg/kg). Oxygenation progressively increased in the SL and SL+L groups over the 4-hour period (at 240 min: C = 99 ± 14; SL = 154 ± 39; SL+L = 230 ± 40 mmHg) (p < 0.05). PaCO2 increased in all groups from 43 ± 0.3 to 55 ± 0.7 mmHg. Only SL+L showed a reduction in PaCO2 (at 240 min: C = 54 ± 4; SL = 53 ± 7; SL+L = 49 ± 2 mmHg) (p < 0.05). Finally, SL and SL + L had superior characteristics during the quasi-static pressure volume (PV) procedure as compared to Control (p < 0.05). In our HCl ALI model, SL improved oxygenation and quasi-static lung compliance over C. The pulmonary function effects of SL were further enhanced by the addition of Lidocaine to the surfactant suspension. Combining therapeutic agents with surfactant lavage may be an effective strategy in ALI.

Pancuronium does not alter the hemodynamic status of piglets after normoxia or hypoxia.

ABSTRACT: Pancuronium is a neuromuscular blocking agent commonly used to eliminate agitation in sick newborn infants requiring mechanical ventilation. Experimental data supporting this method of intervention are controversial, and hemodynamic studies in newborn infants report conflicting results. This study was designed to determine the hemodynamic effects of pancuronium administered under conditions of normoxia, hypoxia, and preexposure to hypoxia in neonatal piglets with normal lungs. After baseline hemodynamic and blood gas measurements were obtained, pancuronium was administered in two i.v. bolus injections of 0.1 mg/kg. Tidal volume and minute ventilation were maintained constant during the experimental procedure by adjusting ventilator settings. Twenty min after pancuronium, no changes from baseline values were found in arterial blood gases, heart rate, cardiac output, mean arterial pressure, systemic vascular resistance, pulmonary artery pressure, pulmonary vascular resistance, central venous pressure, or pulmonary capillary wedge pressure in any of the three conditions studied. In conclusion, pancuronium administered during normoxia, hypoxia, or after preexposure to hypoxia while controlled ventilation is maintained does not alter systemic or pulmonary hemodynamic status of the newborn piglet.