Associations of fluid amount, type, and balance and acute kidney injury in patients undergoing major surgery.

Fluid administration has been reported to be associated with an increased risk of acute kidney injury (AKI). We assessed whether, after correction for fluid balance, amount and chloride content of fluids administered have an independent association with AKI. We performed an observational study in patients after major surgery assessing the independent association of AKI with volume, chloride content and fluid balance, after adjustment for Physiological and Operative Severity Score for enUmeration of Mortality and morbidity (POSSUM) score, age, elective versus emergency surgery, and duration of surgery. We studied 542 consecutive patients undergoing major surgery. Of these, 476 patients had renal function tested as part of routine clinical care and 53 patients (11.1%) developed postoperative AKI. After adjustments, a 100 ml greater mean daily fluid balance was artificially associated with a 5% decrease in the instantaneous hazard of AKI: adjusted Hazard Ratio (aHR) 0.951, 95% confidence intervals (CI) 0.935 to 0.967, P <0.001. However, after adjustment for the proportion of chloride-restrictive fluids, mean daily fluid amounts and balances, POSSUM morbidity, age, duration and emergency status of surgery, and the confounding effect of fluid balance, every 5% increase in the proportion of chloride-liberal fluid administered was associated with an 8% increase in the instantaneous hazard of AKI (aHR 1.079, 95% CI 1.032 to 1.128, P=0.001), and a 100 ml increase in mean daily fluid amount given was associated with a 6% increase in the instantaneous hazard of AKI (aHR 1.061, 95% CI 1.047 to 1.075, P <0.001). After adjusting for key risk factors and for the confounding effect of fluid balance, greater fluid administration and greater administration of chloride-rich fluid were associated with greater risk of AKI.

Does hydrotherapy improve strength and physical function in patients with osteoarthritis--a randomised controlled trial comparing a gym based and a hydrotherapy based strengthening programme.

OBJECTIVE: To compare the effects of a hydrotherapy resistance exercise programme with a gym based resistance exercise programme on strength and function in the treatment of osteoarthritis (OA). DESIGN: Single blind, three arm, randomised controlled trial. SUBJECTS: 105 community living participants aged 50 years and over with clinical OA of the hip or knee. METHODS: Participants were randomised into one of three groups: hydrotherapy (n = 35), gym (n = 35), or control (n = 35). The two exercising groups had three exercise sessions a week for six weeks. At six weeks an independent physiotherapist unaware of the treatment allocation performed all outcome assessments (muscle strength dynamometry, six minute walk test, WOMAC OA Index, total drugs, SF-12 quality of life, Adelaide Activities Profile, and the Arthritis Self-Efficacy Scale). RESULTS: In the gym group both left and right quadriceps significantly increased in strength compared with the control group, and right quadriceps strength was also significantly better than in the hydrotherapy group. The hydrotherapy group increased left quadriceps strength only at follow up, and this was significantly different from the control group. The hydrotherapy group was significantly different from the control group for distance walked and the physical component of the SF-12. The gym group was significantly different from the control group for walk speed and self efficacy satisfaction. Compliance rates were similar for both exercise groups, with 84% of hydrotherapy and 75% of gym sessions attended. There were no differences in drug use between groups over the study period. CONCLUSION: Functional gains were achieved with both exercise programmes compared with the control group.

Integrating baseline health status data collection into the process of care.

BACKGROUND: Health status data are an increasingly important component of outcomes assessment and can be used to facilitate quality assessment and improvement efforts. An enormous challenge to the use of health status data among hospitalized patients, however, is collecting baseline data at the time of treatment, an essential component for risk-adjusting subsequent outcomes. The Mid America Heart Institute of Saint Luke's Hospital (Kansas City, Mo), attempted to integrate the collection of health status assessments within the process of performing coronary revascularization. THE DATA COLLECTION STRATEGY: The data collection strategy was developed for each admission portalelective outpatients (admissions for same-day procedures), inpatients, and emergent cases. Health status data were collected on all patients with coronary artery disease who were receiving a percutaneous coronary intervention or coronary artery bypass graft with no disruption to physician scheduling or nursing staff. RESULTS: In general, patients were agreeable to completing the health status survey. Despite initial efforts to educate the hospital staff about the goal and purpose of health status assessment, staff members who were unaware of the uses of these data seemed to minimize their value. Providing examples of how to use these data relative to the staff member's specific occupational role facilitated buy-in for this project. EPILOGUE: After the pilot study, which lasted until June 1999, data were continually collected for 18 months, through August 2000, even with the cessation of external grant funding for this project. Baseline data collection finally stopped, primarily because of a failure to accommodate data collection into the routine flow of patient care by existing nursing staff.

Autistic disorder and schizophrenia: diagnostic overlaps.

Data on 14 males with autism and 14 with schizophrenia were collected to examine symptom overlap. The Structured Clinical Interview (SCID), the schedule for positive symptoms (SAPS) and the schedule for negative symptoms (SANS) of schizophrenia, the Childhood Autism Rating Scale (CARS), and the DSM-III-R were administered. On the SCID, none of the men with paranoid schizophrenia met criteria for autism while 7 of those with autism met criteria for schizophrenia, disorganized type, showing negative symptoms. In addition, 5 showed positive symptoms on the SAPS and 6 negative symptoms on the SANS. As the difference in measured nonverbal intelligence was not significant, the effects could not be attributed to it. Although the findings continue to support the differentiation of autism and schizophrenia, they are also consistent with a comorbidity of the two disorders, mainly in those diagnosed with autism.

The relative role of ErbB1-4 receptor tyrosine kinases in radiation signal transduction responses of human carcinoma cells.

Activation of the epidermal growth receptor (ErbB1) occurs within minutes of a radiation exposure. Immediate downstream consequences of this activation are currently indistinguishable from those obtained with growth factors (GF), e.g. stimulation of the pro-proliferative mitogen-activated protein kinase (MAPK). To identify potential differences, the effects of GFs and radiation on other members of the ErbB family have been compared in mammary carcinoma cell lines differing in their ErbB expression profiles. Treatment of cells with EGF (ErbB1-specific) or heregulin (ErbB4-specific) resulted in a hierarchic transactivations of ErbB2 and ErbB3 dependent on GF binding specificity. In contrast, radiation indiscriminately activated all ErbB species with the activation profile reflecting that cell's ErbB expression profile. Downstream consequences of these ErbB interactions were examined with MAPK after specifically inhibiting ErbB1 (or 4) with tyrphostin AG1478 or ErbB2 with tyrphostin AG825. MAPK activation by GFs or radiation was completely inhibited by AG1478 indicating total dependance on ErbB1 (or 4) depending on which ErbB is expressed. Inhibiting ErbB2 caused an enhanced MAPK response simulating an amplified ErbB1 (or 4) response. Thus ErbB2 is a modulator of ErbB1 (or 4) function leading to different MAPK response profiles to GF or radiation exposure.

Alzheimer dementia in Down's syndrome: the relevance of cognitive ability.

More years of education have been found to be associated with a lower rate of Alzheimer disease (AD) in individuals without intellectual disability. It has been proposed that education reflects greater 'synaptic reserve' and that greater synaptic reserve may defer the development of AD. The present study compared individuals with Down's syndrome (DS) who were found to have symptoms of dementia with those who remained symptom-free to determine if the two groups differed in their level of education, employment, recreational activities, years in an institution or overall level of cognitive functioning. Thirty-five adults with DS aged between 29 and 67 years were assessed. The participants were recruited from a community health facility and included individuals with a wide range of ability levels. Neuropsychological testing, caregiver report and the Dementia Scale for Down Syndrome (Gedye 1995) were used to identify decline in participants over periods of 6 months to 3 years. After the effect of age was statistically removed, multiple regression analyses revealed that level of cognitive functioning was significantly associated with decline such that a higher level of cognitive functioning predicted less decline. None of the environmental variables (i.e. educational level, years in an institution and employment) were directly associated with decline; however, a post hoc regression using level of cognitive functioning as the outcome variable revealed that level of cognitive functioning itself was associated with these environmental variables. A higher level of cognitive functioning was associated with fewer cases of dementia in individuals with DS, and level of cognitive functioning appears to be associated with environmental factors such as level of education, years in an institution and employment. The present findings suggest that environmental interventions aimed at improving level of cognitive functioning may also be useful in deferring the onset of dementia.

Detection of serial changes in absolute myocardial perfusion with 82Rb PET.

UNLABELLED: Serial changes in myocardial perfusion may represent an important marker of disease progression or regression or the effects of therapy for patients with coronary artery disease (CAD). Quantitative methods have not been developed for the assessment of serial changes in perfusion. The objective of this study was to use receiver operator characteristic (ROC) analysis to determine the sensitivity and specificity of direct paired comparisons (DPCs) to detect changes in absolute myocardial perfusion measured with 82Rb PET. METHODS: Repeated dynamic 82Rb PET scans were obtained on 8 dogs at rest and during hyperemia induced with dobutamine (n = 4) or atrial pacing (n = 4). Radiolabeled microspheres were used to verify perfusion changes. Polar maps of absolute 82Rb retention and associated SD were estimated from the dynamic images. Paired comparisons were then performed using a t test on each of the 532 polar map sectors. Rest-rest and stress-stress differences were used to assess specificity and reproducibility, and stress-rest differences were used to assess sensitivity. RESULTS: 82Rb retention differences of 20% over baseline were detected with 85%-90% sensitivity and specificity, using the optimal DPC probability value and image smoothness. The average 82Rb retention differences correlated well with microspheres (r = 0.74; P = 0.001). Reproducibility of the mean retention values was 4.7% +/- 2.1%. As reproducibility varies, the DPC probability value can be adjusted to maintain specificity. These ROC results are directly applicable to other image modalities that produce measurements with similar SEs (3.7% +/- 0.9%). CONCLUSION: The developed method of DPCs is sensitive and specific for the detection of changes in absolute myocardial perfusion measured with 82Rb PET.

Proinflammatory consequences of transgenic fas ligand expression in the heart.

Expression of Fas ligand (FasL) renders certain tissues immune privileged, but its expression in other tissues can result in severe neutrophil infiltration and tissue destruction. The consequences of enforced FasL expression in striated muscle is particularly controversial. To create a stable reproducible pattern of cardiomyocyte-specific FasL expression, transgenic (Tg) mice were generated that express murine FasL specifically in the heart, where it is not normally expressed. Tg animals are healthy and indistinguishable from nontransgenic littermates. FasL expression in the heart does result in mild leukocyte infiltration, but despite coexpression of Fas and FasL in Tg hearts, neither myocardial tissue apoptosis nor necrosis accompanies the leukocyte infiltration. Instead of tissue destruction, FasL Tg hearts develop mild interstitial fibrosis, functional changes, and cardiac hypertrophy, with corresponding molecular changes in gene expression. Induced expression of the cytokines TNF-alpha, IL-1beta, IL-6, and TGF-beta accompanies these proinflammatory changes. The histologic, functional, and molecular proinflammatory consequences of cardiac FasL expression are transgene-dose dependent. Thus, coexpression of Fas and FasL in the heart results in leukocyte infiltration and hypertrophy, but without the severe tissue destruction observed in other examples of FasL-directed proinflammation. The data suggest that the FasL expression level and other tissue-specific microenvironmental factors can modulate the proinflammatory consequences of FasL.

Experimental evaluation of a model for oxygen exchange in a pulsating intravascular artificial lung.

Intravascular oxygenation and carbon dioxide removal remains a potentially attractive means for respiratory support in patients with acute or chronic respiratory failure. Our group has been developing an intravascular hollow fiber artificial lung that uses a pulsating balloon located within the fiber bundle to augment gas transfer. We previously reported on a simple compartmental model for simulating O2 exchange in pulsating intravascular artificial lungs. In this study we evaluate the O2 exchange model with gas exchange and PO2 measurements performed on an idealized intravascular artificial lung (IIVAL) tested in a water perfusion loop. The IIVAL has well-defined bundle geometry and can be operated in balloon pulsation mode, or a steady perfusion mode for determining the mass transfer correlation required by the model. The O2 exchange rates and compartmental O2 tensions measured with balloon pulsation in the IIVAL are within 10% of model predictions for flow and pulsation conditions relevant to intravascular oxygenation. The experiments confirmed that a significant buildup of PO2 occurs within the fiber bundle, which reduces the O2 exchange rate. The agreement between experiments and predictions suggests that the model captures the cardinal processes dictating gas transfer in pulsating intravascular artificial lungs.

A mathematical model of gas exchange in an intravenous membrane oxygenator.

Acute respiratory distress syndrome (ARDS) is a pulmonary edemic condition which reduces respiratory exchange in 150,000 people per year in the United States. The currently available therapies of mechanical ventilation and extracorporeal membrane oxygenation are associated with high mortality rates, so intravenous oxygenation represents an attractive, alternative support modality. We are developing an intravenous membrane oxygenator (IMO) device intended to provide 50% of basal oxygen and carbon dioxide exchange requirements for ARDS patients. A unique aspect of the IMO is its use of an integral balloon to provide active mixing. This paper describes a mathematical model which was developed to quantify and optimize the gas exchange performance of the IMO. The model focuses on balloon activated mixing, uses a lumped compartment approach, and approximates the blood-side mass transfer coefficients with cross-flow correlations. IMO gas exchange was simulated in water and blood, for a variety of device geometries and balloon pulsation rates. The modeling predicts the following: (1) gas exchange efficiency is reduced by a buildup of oxygen in the fluid near the fibers; (2) the IMO gas exchange rate in blood is normally about twice that in water under comparable conditions; (3) a balloon diameter of about 1.5 cm leads to optimal gas exchange performance: and (4) in vivo positioning can affect gas exchange rates. The numerically predicted gas transfer rates correlate closely with those experimentally measured in vitro for current IMO prototypes.

Development of a low flow resistance intravenous oxygenator.

A potentially attractive support device for patients with acute respiratory failure is an intravenous membrane oxygenator. One problem, however, is that the membrane surface area required for sufficient gas exchange can unduly increase vena caval pressure drop and impede venous return. The purpose of this study was to design and develop an intravenous oxygenator that would offer minimal venous flow resistance in situ. The device uses a constrained fiber bundle of smaller cross sectional size than the vena cava so as to effect an intentional shunt flow of venous blood around the fiber bundle and reduce the venous pressure drop caused by the device. A pulsating balloon within the fiber bundle redirects part of this shunt flow into reciprocating flow in and out of the fiber bundle. This offers dual advantages: 1) Blood flow through the fiber bundle is mainly perpendicular to the fibers; and 2) the requisite energy for driving flow comes largely from the pneumatic system pulsating the balloon, not from a venous pressure drop. In this mode a full length device with a 2 cm fiber bundle in a 2.5 cm blood vessel would offer a pressure drop of only a few millimeters of mercury. The use of constrained fiber bundles requires good uniformity of fiber spacing for effective gas exchange. Several prototypes have been fabricated, and CO2 and O2 exchange rates of up to 402 and 347 ml/min/m2 have been achieved during acute animal implantation.

Recent progress in engineering the Pittsburgh intravenous membrane oxygenator.

The University of Pittsburgh intravenous membrane oxygenator (IMO) is undergoing additional engineering development and characterization. The focus of these efforts is an IMO device that can supply as much as one-half basal O2 consumption and CO2 elimination rates while residing within the inferior and superior vena cavae after peripheral venous insertion. The current IMO design consists of a bundle of hollow fiber membranes potted to manifolds at each end, with an intra-aortic type balloon integrally situated within the fiber bundle. Pulsation of the balloon using helium gas and a balloon pump console promotes fluid and fiber motion and enhances gas exchange. During the past year, more than 15 IMO prototypes have been fabricated and extensively bench tested to characterize O2 gas exchange capacity, balloon inflation/deflation over relevant frequency ranges, and the pneumatics of the sweep gas pathway through the device. The testing has led to several engineering changes, including redesign of the helium and sweep gas pathways within the IMO device. As a result, the maximum rate of balloon pulsation has increased substantially above the previous 70 bpm to 160 bpm, and the vacuum pressure required for sufficient sweep gas flow has been reduced. The recent IMO prototypes have demonstrated an O2 exchange capacity of as much as 90 ml/min/m2 in water, which appears within 70% of our design goal when extrapolated to scaled up devices in blood.

Ultrasound velocity and attenuation at different skeletal sites compared with bone mineral density measured using dual energy X-ray absorptiometry.

Measurements of ultrasound velocity were performed in the tibia in a group of 89 female subjects (mean age 50.6 years). Velocity and broadband ultrasound attenuation (BUA) measurements were performed in the os-calcis in a group of 100 male and female subjects (mean age 55.8 years). Dual energy X-ray absorptiometry (DEXA) scans were also performed on all of these subjects enabling measurements of lumbar spine and femoral neck bone mineral density (BMD) to be obtained. In two small subgroups of the above groups, each comprising 20 subjects, measurements of tibial BMD and os-calcis BMD were also performed. Tibial BMD and ultrasound velocity were found to be well correlated (r = 0.71), although both spine and femoral neck BMD were poorly correlated with ultrasound velocity in the tibia (r = 0.299 and 0.072, respectively). BUA of the os-calcis was moderately correlated with BMD at the same site (r = 0.44) and showed similar or slightly better correlations with BMD measurements of the lumbar spine and femoral neck (r = 0.410 and 0.537, respectively). Ultrasound velocity in the os-calcis was well correlated with os-calcis BMD (r = 0.729) but only moderately correlated with spine and femoral neck BMD (r = 0.470 and 0.498, respectively). This study suggests that BUA and ultrasound velocity measurements of the os-calcis are better predictors of BMD at the critical skeletal sites of the lumbar spine and femoral neck than ultrasound velocity in the tibia. Ultrasound velocity in the tibia and the os-calcis was found to be a good predictor of the BMD in the measured bone.

Factors that affect depth perception in stereoscopic displays.

This study investigated several factors that affect depth perception in stereoscopic displays: half-image separation magnitude, separation direction (crossed vs. uncrossed), viewing distance, stimulus size, and exposure duration. The depth perceived under various combinations of levels of these factors was compared with depth predicted by the geometry of stereopsis. Perceived depth in the crossed-separation direction was frequently close to predictions, such that increases in separation and viewing distance produced appropriate increases in perceived depth. Depth in the uncrossed direction was frequently less than that predicted, especially for small stimuli presented at a long viewing distance, with a large half-image separation, and/or with a brief duration. Thus depth in both crossed and uncrossed directions equaled predictions only for large stimuli exposed for a long duration.

High-pressure liquid-chromatographic separation of lactate dehydrogenase isoenzymes.

The isoenzymes of lactate dehydrogenase (EC 1.1.1.27) were separated with excellent resolution in less than 1 h by high-pressure anion-exchange chromatography. These isoenzymes were determined in some tissue extracts and high-activity serum samples by this technique.

Theory of photometric errors applied to the design and evaluation of a high-performance filter photometer.

We have applied a comprehensive theory of photometric errors to the design and evaluation of an inexpensive stabilized photometer. The photometer is described in terms of a group of modules, the characteristics of which are described in terms of their effect on specific error coefficients. Procedures described in this paper show how the principles described earlier [Clin, Chem. 20, 1028 (1974)] can be used to optimize the design of new instrumentation. Chemical data are included to verify the agreement between predicted and experimental results.