Impact of ontogeny on linezolid disposition in neonates and infants

The impact of age on linezolid disposition during the first few months of life has not been previously investigated. We characterized linezolid pharmacokinetics after a single, 10.0-mg/kg intravenous dose in 42 infants stratified as follows: group 1 (n = 9), gestational age <34 weeks and postnatal age <8 days; group 2 (n = 7), gestational age <34 weeks and postnatal age 8 days to 12 weeks; group 3 (n = 11), gestational age >or=34 weeks and postnatal age <8 days; and group 4 (n = 15), gestational age >or=34 weeks and postnatal age 8 days to 12 weeks. Linezolid was quantitated by a validated HPLC-triple-quadrupole mass spectrometer method from repeated blood samples (n = 7, 0.3 mL each) obtained over a 12-hour period. Pharmacokinetic parameters were determined by standard model-dependent techniques. The values (mean +/- SD) for total body clearance (CL) (0.25 +/- 0.12 L x h(-1) x kg(-1)), apparent volume of distribution (VD(ss)) (0.75 +/- 0.19 L/kg), and elimination half-life (t(1/2)) (2.8 +/- 2.1 hours) from the entire study cohort were similar to values reported previously for children and adolescents. Examination of the linezolid pharmacokinetics as a function of age revealed that CL increased rapidly during the first week of life and as a function of postnatal age. Age stratification revealed lower values for CL in those infants aged less than 8 days (group 1, 0.12 +/- 0.06 L x h(-1) x kg(-1); group 3, 0.23 +/- 0.12 L x h(-1) x kg(-1)) as compared with those aged 8 days to 12 weeks (group 2, 0.31 +/- 0.07 L x h(-1) x kg(-1); group 4, 0.31 +/- 0.10 L x h(-1) x kg(-1)). In contrast to the results for CL, gestational age served to be the most useful predictor of VD(ss). Evaluation of the pharmacokinetic data would appear to support the use of linezolid dosing regimens currently approved for infants and young children in neonates with postnatal age greater than 7 days.     

The relationship between distance to hospital and patient mortality in emergencies: an observational study

Objectives

Reconfiguration of emergency services could lead to patients with life‐threatening conditions travelling longer distances to hospital. Concerns have been raised that this could increase the risk of death. We aimed to determine whether distance to hospital was associated with mortality in patients with life‐threatening emergencies.

Methods

We undertook an observational cohort study of 10 315 cases transported with a potentially life‐threatening condition (excluding cardiac arrests) by four English ambulance services to associated acute hospitals, to determine whether distance to hospital was associated with mortality, after adjustment for age, sex, clinical category and illness severity.

Results

Straight‐line ambulance journey distances ranged from 0 to 58 km with a median of 5 km, and 644 patients died (6.2%). Increased distance was associated with increased risk of death (odds ratio 1.02 per kilometre; 95% CI 1.01 to 1.03; p<0.001). This association was not changed by adjustment for confounding by age, sex, clinical category or illness severity. Patients with respiratory emergencies showed the greatest association between distance and mortality.

Conclusion

Increased journey distance to hospital appears to be associated with increased risk of mortality. Our data suggest that a 10‐km increase in straight‐line distance is associated with around a 1% absolute increase in mortality.     

Patient and Primary Care Physician Satisfaction with Chest Pain Unit and Routine Care

OBJECTIVES: The chest pain unit (CPU) has been developed to improve care for patients with acute, undifferentiated chest pain. The authors aimed to measure patient and primary care physician (PCP) satisfaction with CPU care and routine care and to determine whether patient satisfaction predicted PCP satisfaction. METHODS: A CPU was established, and 442 days were randomly allocated to either CPU care or routine care. Consenting patients presenting with acute, undifferentiated chest pain were recruited and followed at two days and one month. All were given a self-completed patient satisfaction questionnaire two days after attendance (N = 972). Each patient's PCP was sent a self-completed satisfaction questionnaire during days 171-442 of the trial (N = 601). Analysis determined whether CPU care was associated with improved patient or PCP satisfaction and whether patient satisfaction predicted PCP satisfaction for three questions relating to diagnosis, treatment, and overall care. RESULTS: CPU care was consistently associated with higher scores across all patient satisfaction questions, from the perceived thoroughness of examination to care received to an overall assessment of the service received. However, CPU care achieved small improvements in only two of ten PCP satisfaction questions, concerning overall management of the patient and the amount of information about investigations performed. Furthermore, patient satisfaction did not predict PCP satisfaction in relation to diagnosis (p = 0.456), treatment (p = 0.256), or overall care (p = 0.085). CONCLUSIONS: CPU care is associated with substantial improvements in all dimensions of patient satisfaction but only minimal improvements in PCP satisfaction. Patient satisfaction was not a strong predictor of PCP satisfaction with emergency care.     

Peptidoglycan of S. aureus causes increased levels of matrix metalloproteinases in the rat

Matrix metalloproteinases (MMPs) have been suggested to contribute to the organ injury in septic patients. We recently demonstrated that peptidoglycan (PepG) of S. aureus causes organ injury in the rat. A possible role for MMPs in the septic response to PepG is unknown. In the present study, we have examined whether the release of MMP-9 (gelatinase B) and MMP-2 (gelatinase A) is induced by PepG in the anesthetized rat. Male Wistar rats were injected intravenously with PepG (10 mg/kg), LPS (1 mg/kg), or a combination of LPS and PepG (1 mg/kg of each). After 1 or 3 h, liver, lung, and plasma were harvested. MMP-9 and MMP-2 levels were analyzed in organ homogenates and in plasma samples by zymography. MMP-9 levels were significantly increased in the lung within 1 h after injection of PepG, LPS, or combined treatment, compared with sham animals (P < or = 0.05). In the liver and plasma, MMP-9 was clearly increased by PepG or LPS at both 1 and 3 h compared with sham animals (P < or = 0.05). Considerable basal amounts of MMP-2 protein were seen in the liver and in plasma. In the lung, MMP-2 levels were elevated by combined LPS/PepG at 1 h and by LPS at 3 h (P < or = 0.05). In contrast, MMP-2 activity in the liver was significantly reduced by bacterial products. In the plasma, no major alterations of MMP-2 levels were observed. Our data show that PepG of S. aureus causes a rapid elevation of MMP-9 protein in the liver, lung, and blood of the rat. Based on these and previous data, we hypothesize that the release of MMP-9 in lung, liver, and blood is part of the septic host response to systemic PepG.     

Use of spiral computed tomography contrast angiography and ultrasonography to exclude the diagnosis of pulmonary embolism in the emergency department

Spiral computed tomography (CT) contrast angiography is a promising imaging modality for the diagnosis of pulmonary embolism but the negative predictive value of this test remains controversial. We performed a multi-center prospective cohort study to determine the safety of relying on a negative spiral CT contrast angiography scan to exclude pulmonary embolism. Patients presenting to the Emergency Departments of three tertiary care institutions with clinically suspected pulmonary embolism were potentially eligible for the study. Patients underwent a clinical evaluation to categorize pretest probability into low, moderate, and high categories, and had D-dimer testing performed. Patients at low pretest probability with normal D-dimer were considered to have pulmonary embolism excluded. The remaining patients underwent spiral CT contrast angiography scan of the pulmonary arterial circulation and bilateral venous ultrasound of the proximal leg veins. Patients who were confirmed to have pulmonary embolism or deep vein thrombosis were treated with anticoagulant therapy. Patients in whom the diagnosis of pulmonary embolism was excluded did not receive anticoagulant therapy and were followed for a 3-month period for the development of venous thromboembolic complications. Eight hundred fifty-eight (858) patients were enrolled in this study. Three-hundred sixty-nine (369) patients had low pretest probability and negative D-dimer results and no further diagnostic tests were performed. None of these patients subsequently developed venous thromboembolic complications (0%, 95% confidence interval [CI] 0% to 1.0%). The remaining 489 were referred for spiral CT contrast angiography scan and ultrasound. Sixty-seven patients were confirmed to have pulmonary embolism and an additional 15 patients with negative CT scans had proximal deep vein thrombosis (DVT) on ultrasound for a total prevalence of venous thromboembolism of 82/489 (16.8%). Two of 409 patients who had pulmonary embolism excluded in the initial evaluation phase developed proximal venous thromboembolism (0.5%; 95% CI 0% to 1.8%) in the 3-month follow-up period. These findings suggest that the combination of a negative spiral CT contrast angiography scan and normal venous ultrasound imaging safely excludes the diagnosis of pulmonary embolism in the Emergency Department setting.     

The multifaceted influence of gender in career progress in nursing

The complex web of gender influence in the workplace results from a multifaceted interplay of factors [Walby et al. (1994) Medicine and Nursing. Sage Publications, London]. Literature reports that in nursing men's success compared with that of women is disproportionate and substantial evidence of gender-based disadvantage is found [Women in Management Review13 (1998) 184]. However, studies have not addressed the specific reasons for this and little is known of how or what influences nurses' career decisions and developments [Journal of Advanced Nursing25 (1997) 602]. Those studies which examine career developments and patterns are mainly found in the private business sector.     

BMX‐001, a novel redox‐active metalloporphyrin,improves islet function and engraftment in a murine transplant model

Islet transplantation has become a well‐established therapy for select patients with type 1 diabetes. Viability and engraftment can be compromised by the generation of oxidative stress encountered during isolation and culture. We evaluated whether the administration of BMX‐001 (MnTnBuOE‐2‐PyP⁵⁺ [Mn(III) meso‐tetrakis‐(N‐ b ‐butoxyethylpyridinium‐2‐yl)porphyrin]) and its earlier derivative, BMX‐010 (MnTE‐2‐PyP [Mn(III) meso‐tetrakis‐(N‐methylpyridinium‐2‐yl)porphyrin]) could improve islet function and engraftment outcomes. Long‐term culture of human islets with BMX‐001, but not BMX‐010, exhibited preserved in vitro viability. Murine islets isolated and cultured for 24 hours with 34 μmol/L BMX‐001 exhibited improved insulin secretion (n = 3 isolations, P < .05) in response to glucose relative to control islets. In addition, 34 μmol/L BMX‐001–supplemented murine islets exhibited significantly reduced apoptosis as indicated by terminal deoxynucleotidyl transferase dUTP nick end labeling, compared with nontreated control islets (P < .05). Murine syngeneic islets transplanted under the kidney capsule at a marginal dose of 150 islets revealed 58% of 34 μmol/L BMX‐001–treated islet recipients became euglycemic (n = 11 of 19) compared with 19% of nontreated control islet recipients (n = 3 of 19, P < .05). Of murine recipients receiving a marginal dose of human islets cultured with 34 μmol/L BMX‐001, 92% (n = 12 of 13) achieved euglycemia compared with 57% of control recipients (n = 8 of 14, P = .11). These results demonstrate that the administration of BMX‐001 enhances in vitro viability and augments murine marginal islet mass engraftment.     

Sonography of Fat Necrosis Involving the Extremity and Torso With Magnetic Resonance Imaging and Histologic Correlation

Objective. The purpose of this study was to describe the sonographic appearance of pathologically proven isolated fat necrosis involving the extremities or torso with magnetic resonance imaging (MRI) correlation. Methods. A query of the Department of Pathology database at our institution for the diagnosis of fat necrosis resulted in 1539 cases. Review of the cases and medical records excluded cases without sonographic imaging, those involving the breast, and those within or adjacent to a primary process, including masses or prior surgery, which resulted in a total of 5 cases of primary fat necrosis, 2 of which were evaluated with MRI. Sonograms were reviewed by 2 musculoskeletal radiologists and characterized with regard to location, echogenicity, shadowing, posterior through‐transmission, a hypoechoic rim or halo, definition of borders, homogeneity, a mass effect, and vascularity. The patient medical records, histologic results, and MRI findings were also reviewed. Results. Of the 5 cases of isolated fat necrosis, 2 involved the torso and 3 the lower extremities. On sonography, all were located in the subcutaneous fat; 2 were isoechoic; 3 were hyperechoic; 2 had a hypoechoic halo; none showed shadowing or posterior through‐transmission; 2 were well defined; 3 were masslike; 4 were heterogeneous; and 2 showed increased flow on color or power Doppler imaging. Magnetic resonance imaging showed an intermediate signal and either diffuse or ring enhancement. Conclusions. Isolated fat necrosis of the extremities and torso had 2 sonographic appearances, which included a well‐defined isoechoic mass with a hypoechoic halo and a poorly defined hyperechoic region in the subcutaneous fat.