Staphylococcus aureus AbcA transporter enhances persister formation under ß-lactam exposure.

We evaluated the role of Staphylococcus aureus AbcA transporter in bacterial persistence and survival following exposure to the bactericidal agents nafcillin and oxacillin at both the population and single-cell levels. We show that AbcA overexpression resulted in resistance to nafcillin but not oxacillin. Using distinct fluorescent reporters of cell viability and AbcA expression, we found that over 6-14 hours of persistence formation, the proportion of AbcA reporter-expressing cells assessed by confocal microscopy increased sixfold as cell viability reporters decreased. Similarly, single-cell analysis in a high-throughput microfluidic system found a strong correspondence between antibiotic exposure and AbcA reporter expression. Persister cells grown in the absence of antibiotics showed neither an increase in nafcillin MIC nor in abcA transcript levels, indicating that survival was not associated with stable mutational resistance or abcA overexpression. Furthermore, persister cell levels on exposure to 1×MIC and 25×MIC of nafcillin decreased in an abcA knockout mutant. Survivors of nafcillin and oxacillin treatment overexpressed transporter AbcA, contributing to an enrichment of the number of persisters during treatment with pump-substrate nafcillin but not with pump-non-substrate oxacillin, indicating that efflux pump expression can contribute selectively to the survival of a persister population.

Staphylococcus aureus Efflux Pumps and Tolerance to Ciprofloxacin and Chlorhexidine following Induction by Mupirocin.

Mupirocin induced expression of genes encoding efflux pumps NorA and MepA as well as a yellow fluorescent protein (YFP) fluorescence reporter of NorA. Mupirocin exposure also produced reduced susceptibility to pump substrates ciprofloxacin and chlorhexidine, a change that was dependent on intact norA and mepA, respectively.

Index-based dietary patterns and risk of colorectal cancer: the NIH-AARP Diet and Health Study.

The authors compared how four indexes-the Healthy Eating Index-2005, Alternate Healthy Eating Index, Mediterranean Diet Score, and Recommended Food Score-are associated with colorectal cancer in the National Institutes of Health-AARP Diet and Health Study (n = 492,382). To calculate each score, they merged data from a 124-item food frequency questionnaire completed at study entry (1995-1996) with the MyPyramid Equivalents Database (version 1.0). Other variables included energy, nutrients, multivitamins, and alcohol. Models were stratified by sex and adjusted for age, ethnicity, education, body mass index, smoking, physical activity, and menopausal hormone therapy (in women). During 5 years of follow-up, 3,110 incident colorectal cancer cases were ascertained. Although the indexes differ in design, a similarly decreased risk of colorectal cancer was observed across all indexes for men when comparing the highest scores with the lowest: Healthy Eating Index-2005 (relative risk (RR) = 0.72, 95% confidence interval (CI): 0.62, 0.83); Alternate Healthy Eating Index (RR = 0.70, 95% CI: 0.61, 0.81); Mediterranean Diet Score (RR = 0.72, 95% CI: 0.63, 0.83); and Recommended Food Score (RR = 0.75, 95% CI: 0.65, 0.87). For women, a significantly decreased risk was found with the Healthy Eating Index-2005, although Alternate Healthy Eating Index results were similar. Index-based dietary patterns that are consistent with given dietary guidelines are associated with reduced risk.

Index-based dietary patterns and risk of lung cancer in the NIH-AARP diet and health study.

BACKGROUND/OBJECTIVES: Dietary pattern analysis considers combinations of food intake and may offer a better measure to assess diet-cancer associations than examining individual foods or nutrients. Although tobacco exposure is the major risk factor for lung cancer, few studies have examined whether dietary patterns, based on preexisting dietary guidelines, influence lung cancer risk. After controlling for smoking, we examined associations between four diet quality indices-Healthy Eating Index-2010 (HEI-2010), Alternate Healthy Eating Index-2010 (AHEI-2010), alternate Mediterranean Diet score (aMED) and Dietary Approaches to Stop Hypertension (DASH)-and lung cancer risk in the NIH-AARP (National Institutes of Health-American Association of Retired Persons) Diet and Health study. SUBJECTS/METHODS: Baseline dietary intake was assessed in 460 770 participants. Over a median of 10.5 years of follow-up, 9272 incident lung cancer cases occurred. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and confidence intervals (CIs). RESULTS: Comparing highest to lowest quintiles, HRs (95% CIs) for lung cancer were as follows: HEI-2010=0.83 (0.77-0.89), AHEI-2010=0.86 (0.80-0.92), aMED=0.85 (0.79-0.91) and DASH=0.84 (0.78-0.90). Among the individual components of the dietary indices, higher consumption of whole grains and fruits was significantly inversely associated with lung cancer risk for several of the diet indices. Total index score analyses stratified by smoking status showed inverse associations with lung cancer for former smokers; however, only HEI-2010 was inversely associated in current smokers and no index score was inversely associated among never smokers. CONCLUSIONS: Although smoking is the factor most strongly associated with lung cancer, this study adds to a growing body of evidence that diet may have a modest role in reducing lung cancer risk, especially among former smokers.

Microvascular pulmonary emboli secondary to precipitated crystals in a patient receiving total parenteral nutrition: a case report and description of the high-resolution CT findings.

A patient with a history of a small-bowel transplant that was subsequently resected required total parenteral nutrition for nutritional supplementation. While receiving therapy, he developed chest tightness, shortness of breath, and fever. The chest radiograph showed bilateral reticulonodular opacities, and the high-resolution CT scan demonstrated diffuse, poorly marginated micronodular opacities in a miliary pattern. Pathology specimens obtained by transbronchial biopsy revealed amorphous material obstructing the pulmonary microvasculature. Microvascular emboli secondary to precipitated crystals is a potential complication of total parenteral nutrition. An awareness of the factors that influence crystal solubility may prevent adverse interactions in patients who require parenteral nutrition.

Status I heart transplant patients: conventional versus ventricular assist device support.

Since 1985, 59 United Network for Organ Sharing status I patients have been considered for heart transplantation. Thirty-four patients were supported with drugs and/or intraaortic balloon pump (IABP) (group I). Twenty-five patients were supported with ventricular assist devices (VADs, group II). Forty percent of the patients in each group died before transplantation. Of the 20 group I patients who underwent transplantation, all received inotropic drugs, and five also required IABPs. All 14 group II patients who underwent transplantation were bridged with VADs. No difference was found in age, sex, or cause of disease between the groups. Complications after transplantation were more common in group I. Fourteen group I patients (70%) and 14 group II patients (100%) were discharged from the hospital (p = 0.03). One year after transplantation, mean left ventricular ejection fraction by cardiac catheterization was 53% in group I (12 patients) and 72% in group II (11 patients; p = 0.0008). Although VAD support does not insure transplantation, it strongly favors transplantation survival in status I patients. These data further suggest an advantage of VAD support for long-term survival.

Univentricular versus biventricular assist device support.

Controversy continues over whether patients should receive selective univentricular assist devices (UVADs) or biventricular assist devices (BVADs). Data from 39 patients supported for more than 2 days with Thoratec VADs were analyzed to compare mortality and morbidity between those receiving UVAD versus BVAD. Twenty-three patients received UVADs and 16 BVADs. Age, gender, and duration of support did not differ significantly between the two groups. Morbidity in VAD patients does not differ between UVAD and BVAD support. Survival is determined by the reversibility of pre-VAD myocardial damage or the eligibility for transplantation, rather than by the number of devices used. These data do not support the use of BVAD in all patients; they support a selective approach based on hemodynamic requirements.

Heart transplantation charges: status 1 versus status 2 patients.

BACKGROUND: The current health care environment mandates closer scrutiny of health care dollar allocation. To better understand the distribution of heart transplantation costs, we reviewed hospital and physician billing of patients who underwent orthotopic heart transplantation between August 1988 and September 1993. METHODS: This study is a retrospective review of 107 consecutive cases. Charges and clinical results of United Network for Organ Sharing status 1 patients (n = 46), including 17 bridge to transplantation patients, were compared with those of United Network for Organ Sharing status 2 patients (n = 57). Charges were converted to 1992 dollars. RESULTS: During the first 12 months of the study, 77% of heart transplantations were performed in United Network for Organ Sharing status 2 patients, whereas over the last 12-month period, 25% of the transplantations were performed in status 2 patients. No significant differences were found in age, gender, type of cardiomyopathy, or survival between the status 1 and status 2 groups. The length of hospitalization for the status 1 group ranged from 8 to 138 days (mean 49 days) as opposed to 5 to 82 days (mean 17.5 days) for the status 2 group (p < 0.0001). Pretransplantation hospital charges were significantly higher for the status 1 group ($47,917 to $341,215, mean $109,116) when compared with status 2 ($0 to $10,035, mean $250) (p < 0.0001). No significant difference was found in posttransplantation hospital charges between status 1 ($47,917 to $210,027, mean $95,379) and status 2 patients ($48,093 to $380,745, mean $102,265). Total charges were significantly higher (p < 0.0001) for the status 1 group ($89,910 to $512,331, mean $239,375) when compared with the status 2 group ($63,885 to $455,680, mean $128,594). Total transplantation charges for the study period were $18,341,108. This amount could have paid for 77 status 1 transplantations or 143 status 2 transplantations. CONCLUSIONS: If current trends continue and the donor pool remains the same, most transplant recipients will be status 1, resulting in a comparable number of transplantations performed at twice the charges.

Endogenous Pseudomonas aeruginosa endophthalmitis: a case report and literature review.

Endogenous endophthalmitis is a vision-threatening condition that results from the hematogenous spread of infection to the eye that originated in a distant primary focus. Although it has long been recognized that bloodborne organisms can infect the eye, endogenous bacterial endophthalmitis is considered a rare entity. We present a unique case of a critically ill patient with a cholangiocarcinoma complicated by ascending cholangitis who developed endogenous Pseudomonas aeruginosa endophthalmitis. An awareness of the risk factors predisposing to endogenous endophthalmitis and a high clinical suspicion are necessary to make an early diagnosis in the intensive care unit. Management involves an aggressive combined medical and surgical approach in an effort to prevent ocular morbidity and vision loss.

Effects of intraaortic balloon position on renal artery blood flow.

Debate continues over what happens to renal blood flow when intraaortic balloons are adjacent to the renal arteries. Fourteen dogs were prepared by implanting instruments to measure heart rate; right atrial, pulmonary arterial, carotid arterial, and femoral arterial pressures; cardiac index; mixed venous oxygen saturation; urine output; and left and right renal blood flows. A 12-mL intraaortic balloon was inserted through the left (n = 9) or right (n = 5) femoral artery. The position of the balloon was randomized so that it was initially placed in either the control (thoracic) or renal position (at the level of the renal arteries). Intraaortic balloon pumping was performed for 4 hours in each position. In 8 dogs, at least one of the renal arteries had partial occlusion, 23% to 98% decrease in flow (mean decrease, 66%), while the intraaortic balloon was in the renal position. An intraaortic balloon in the renal position results in lower renal blood flow as well as a high risk (57%) of selective renal artery occlusion. Decreased renal blood flow is not apparent using conventional monitoring, as hemodynamics do not change.

Nursing care of the patient with an intravascular oxygenator.

Conventional therapy in the management of adult respiratory distress syndrome is often associated with an increased mortality rate. Several methods to improve survival in patients with severe respiratory insufficiency are under evaluation. One recently developed method of treatment is an implantable intravascular oxygenator, which provides supplemental gas exchange for failing lungs. This device can provide temporary ventilatory support in patients with acute, potentially reversible respiratory insufficiency. Reduction in ventilator settings such as airway pressure, oxygen concentration, positive end-expiratory pressure and minute volume can be achieved, decreasing the likelihood of oxygen toxicity and barotrauma. Success of the intravascular oxygenator in adult respiratory distress syndrome is dependent in part on critical care staff expertise. Therefore, a thorough understanding of the operation of this device and its role in acute respiratory failure is necessary for optimal care.

Transfer of a patient with a ventricular assist device to a non-critical care area.

Ventricular assist device (VAD) support has traditionally been associated with critically ill patients. Indeed, a VAD is inserted as the last hope for patients with cardiogenic shock who are unresponsive to conventional therapy. However, many patients bridged to potential cardiac transplantation are no longer critically ill after hemodynamic stabilization is achieved with VAD support. The focus of this article is to provide guidelines established for the transfer and provision of quality nursing care for patients with a VAD on a general cardiothoracic nursing floor.

Mechanical cardiopulmonary support for refractory cardiogenic shock.

From February 1982 to February 1990, 38 patients (30 male patients and 8 female patients) ranging in age from 10 to 78 years (mean 49.4 years) have been supported with arteriovenous extracorporeal membrane oxygenation (ECMO) at St. Louis University Medical Center as a resuscitative system for cardiac arrest or cardiogenic shock. All patients were unresponsive to conventional resuscitative measures including an intraaortic balloon pump in 25 patients. Patients were resuscitated in the intensive care unit, cardiac catheterization laboratory, or the emergency department. Diagnosis varied from acute myocardial infarctions (12 patients), ischemic disease (15 patients), end-stage cardiomyopathy (7 patients), congenital heart disease (3 patients), or postoperative cardiac transplant graft rejection (1 patient). Three patients could not be resuscitated with ECMO because of low flow, but the remaining 35 (92%) achieved hemodynamic stability with ECMO flows greater than 2 L/min/m2. Duration of support ranged from 0.5 to 130 hours (mean 28 hours). Twenty-four patients were successfully weaned from ECMO support after coronary artery bypass (five patients), cardiac transplantation (two patients), or ventricular assist device insertion (eight patients), or with inotropic support (nine patients). Of the 14 patients not weaned, three were inadequately resuscitated, two had percutaneous transluminal coronary angioplasty while receiving ECMO, and nine were not candidates for further intervention. Nine (24%) patients were discharged and are long-term survivors. Our results indicate that resuscitative ECMO is useful for intervals of 12 to 24 hours and can best be applied with (1) patients younger than 60 years of age; (2) patients having acute events (failed percutaneous transluminal coronary angioplasty) amenable to surgical intervention; and (3) candidates for cardiac transplantation who could be switched to more sophisticated devices within 12 to 24 hours of ECMO insertion. With these criteria, ECMO, when used as a resuscitative system, can result in increased survival in selected patients with refractory cardiogenic shock or cardiac arrest.

The importance of patient mobility with ventricular assist device support.

Patients bridged to transplantation with ventricular assist devices (VADs) often require prolonged support. To reduce complications associated with bed rest, the authors developed a program to mobilize patients with VADs. Between August 1986 and May 1992, 25 men and 7 women aged 12-65 years (mean: 42.4 years) were bridged for possible transplantation. The 32 patients were supported with either a Novacor (n = 9) or a Thoratec (n = 23) VAD. Thirty-one patients were turned within 2-12 hr of VAD insertion and received range of motion therapy. Twenty-six patients sat in a chair 2-16 days (mean: 5 days) after VAD insertion. Twenty-one patients used a stationary bicycle, and 23 patients were ambulatory 3-57 days (mean: 11 days) after VAD insertion. Two patients were transplanted within 72 hr of device insertion. Twenty-one of the 23 ambulatory patients were successfully transplanted or weaned from the VAD and discharged from the hospital. Two ambulatory patients who were difficult to rehabilitate (ambulatory 22 and 57 days, respectively, after VAD insertion) died before transplantation. In conclusion, VAD patients should be mobilized early because the VAD can improve exercise capability and survival rate.

Evaluation of an implantable ventricular assist system for humans with chronic refractory heart failure. Measuring quality of life.

The development of a multidimensional quality of life protocol to be used in a clinical trial of an LVAS was presented. The complexity of the new LVAS technology being evaluated added a unique dimension for HQL assessment. The rationale and procedures used in developing this protocol were described. Although we have elucidated the development of a protocol for a specific clinical trial, the principles and procedures employed are widely applicable. To summarize, these procedures are as follows: 1. Determine what quality of life domains are important to measure. This decision should be based upon the domains expected to be affected by treatment, those expected to change as a result of the natural course of the disease or condition, and those that may be affected by changes in the primary domains. 2. Once the domains are selected, identify specific measures for these domains. Where possible, the measures chosen should be standardized, well validated, and appropriate to the study population. Instrument length and mode of administration are additional considerations. 3. Consider any unique aspects of the study population or intervention and develop specific questions to address them. 4. Identify and measure important variables that may moderate or influence quality of life. 5. Test the protocol on an appropriate population for length, flow, and ease of administration. Copies of the complete HQL protocol are available by writing to: Dr. Nancy Avis, New England Research Institute, 9 Galen Street, Watertown, MA 02172.

Hemodynamic predictors for weaning patients from ventricular assist devices (VADs).

In order to find hemodynamic parameters that can accurately predict whether patients can be successfully weaned from ventricular assist devices (VADs), we studied data from 17 patients supported with Pierce-Donachy VADs [11 left VAD (LVAD); 6 right VAD (RVAD)] following cardiogenic shock for periods from 1.3 to 22 days (mean 5.4). Myocardial recovery was determined by daily measurements of "pump on pump off" parameters, and the data from the 8 LVAD patients and 3 RVAD patients whose hearts recovered were compared to the data from those whose did not. In this study, daily pump on pump off hemodynamic measurements were found to be predictive of success for weaning patients from VADs. In particular, the most significant predictors were: increases in mixed venous oxygen saturation, cardiac index, mean arterial pressure and ventricular ejection fraction, as well as decreases in atrial pressures. An index for measuring hemodynamic function with the VAD off is proposed, as are models of recovery. Seventy percent of the patients weaned from VADs survived, indicating that patients appropriately weaned from VAD support have a reasonable chance for survival.

Team approach to circulatory support.

A multidisciplinary approach to circulatory support is discussed in this article. The clinical, educational, and investigational responsibilities of each team member are presented.

Nursing care of a patient requiring prolonged mechanical circulatory support.

Four cardiac transplant candidates were supported with ventricular assist devices for periods ranging from 53 to 90 days (mean, 75 days). The patients were men who ranged in age from 36 to 49 years (mean, 44.5 years). Two patients had Pierce-Donachy biventricular assist devices (BVADs) and two patients had Novacor left ventricular assist systems (LVASs). Complications included infection (3 patients), development of antibodies (2 patients), bleeding (2 patients), and pump inflow obstruction (1 patient). All patients were maintained on an anticoagulation regimen which included warfarin and dipyridamole. They were extubated and ambulatory for most of the period of mechanical support. Thromboembolic complications did not develop in any of these patients, and they did not acquire infections which involved the mediastinum. They were successfully transplanted and discharged 11 to 25 days after transplantation. Although major complications were common in this small group of patients, all four patients achieved hemodynamic stability and became excellent candidates for cardiac transplantation. With proper patient selection and meticulous nursing care, current mechanical circulatory support technology is capable of maintaining patients consistently for periods of greater than 50 days.

Civil rights extended to disabled.

Largely unnoticed for more than a quarter century, disabilities groups have waged a fight to extend equal rights and opportunities protection to an estimated 43 million Americans with disabilities. On July 26, 1990, President Bush signed landmark legislation dear to the disabled into law. To ensure an easier and smoother transition and compliance for their organizations, physician executives should have a general understanding of the law and its ramifications.