Urinary biomarkers of early renal injury in antiretroviral-naïve HIV-positive persons in Shanghai, China: comparison with the general population.

OBJECTIVES: People living with HIV (PLWH) have a high risk of kidney injury. Measurement of serum creatinine, along with proteinuria, is not sensitive to detect early kidney injury. Here, we investigated novel urinary biomarkers of early renal injury in PLWH. METHODS: We performed a cross-sectional study of 166 antiretroviral-naïve PLWH and 99 HIV-negative persons who all had an estimated glomerular filtration rate > 90 mL/min/1.73 m2 . We compared the levels of seven urinary biomarkers between the two groups using the propensity score matching (PSM) approach and explored the risk factors associated with elevated urinary biomarkers in PLWH. RESULTS: Eighty-three pairs were successfully matched based on PSM. Compared with the HIV-negative group, the HIV-positive group had higher ratios of N-acetyl-ß-D-glucosaminidase (NAG) to urine creatinine (UCr), alpha1-microglobulin (α1-M) to UCr, kidney injury marker-1 (KIM-1) to UCr, neutrophil gelatinase-associated lipocalin to UCr, and epidermal growth factor to UCr, whereas the Tamm-Horsfall protein to UCr ratio and the abnormal albumin to UCr ratio were not significantly different. Positive correlations were observed between HIV RNA level and NAG: UCr (rs  = 0.32; P < 0.001) and α1-M:UCr (rs  = 0.24; P = 0.002) ratios, and negative correlations were observed between CD4 cell count and NAG:UCr (rs  = -0.34; P < 0.001), KIM-1:UCr (rs  = -0.16; P = 0.042) and α1-M:UCr (rs  = -0.36; P < 0.001) ratios. In multivariate linear regression analyses, older age, lower total cholesterol and higher HIV RNA were independently associated with higher NAG:UCr; older age, lower total cholesterol and lower CD4 cell count were independently associated with higher α1-M:UCr. CONCLUSIONS: In comparioson with HIV-negative participants, PLWH were more likely to have tubular injury. Early antiretroviral treatment might mitigate the development of kidney injury.

HIV-associated wasting in the HAART era: guidelines for assessment, diagnosis, and treatment.

Wasting (malnutrition) and lipodystrophy are the two major nutritional alterations in human immunodeficiency virus (HIV)-infected individuals. Both wasting and lipodystrophy may involve a decrease in body fat content, while wasting-but not lipodystrophy-also includes the loss of lean body mass. Lipodystrophy has made the identification of wasting increasingly more difficult. The diagnosis of wasting depends on a definition of the condition that takes into account sex and cultural differences, as well as measurements of body cell mass. Patient management involves a concurrent, comprehensive approach designed to restore lost body cell mass and weight. The authors make recommendations for defining, diagnosing, and treating HIV-associated wasting. Specific therapies include testosterone replacement, other anabolic steroids, and recombinant human growth hormone. Other adjunctive measures, such as progressive resistance exercise and cytokine modulation, may also be utilized. Expected outcomes from effective treatment include restored body cell mass, improvement in quality of life, and reduced rates of hospitalization. Future directions for research should address the need for optimal treatment strategies.

Partnerships in health care: creating a strong value chain.

The health care climate is one of stormy relations between various entities. Employers, managed care organizations, hospitals, and physicians battle over premiums, inpatient rates, fee schedules, and percent of premium dollars. Patients are angry at health plans over problems with access, choice, and quality of care. Employers dicker with managed care organizations over prices, benefits, and access. Hospitals struggle to maintain operations, as occupancy rates decline and the shift to ambulatory care continues. Physicians strive to assure their patients get quality care while they try to maintain stable incomes. Businesses, faced with similar challenges in the competitive marketplace, have formed partnerships for mutual benefit. Successful partnerships are based upon trust and the concept of "win-win." Communication, ongoing evaluation, long-term relations, and shared values are also essential. In Japan, the keiretsu contains the elements of a bonafide partnership. Examples in U.S. businesses abound. In health care, partnerships will improve quality and access. When health care purchasers and providers link together, these partnerships create a new value chain that has patients as the focal point.

Accuracy and utility of a continuous intra-arterial blood gas monitoring system in pediatric patients.

OBJECTIVES: To determine the accuracy of the Paratrend 7 continuous intra-arterial blood gas monitor (CI-ABGM) in radial and femoral artery catheters placed in children compared with simultaneous measurements of pH, Pa(CO2), and Pa(O2) performed by intermittent blood gas analysis. To determine sensor longevity in pediatric patients at different arterial sites. To determine the utility of CI-ABGM for tracking unanticipated events related to blood gas deterioration. SETTING: A pediatric intensive care unit of a university hospital. DESIGN: A prospective clinical investigation. PATIENTS: Fifty critically ill pediatric patients, ranging in age from 1 wk to 18 yrs of age, who required either radial or femoral artery catheters for intermittent arterial blood gas monitoring. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A Paratrend 7 intra-arterial sensor was placed through either an 18- or 20-gauge catheter previously inserted into the radial or femoral artery. At clinically predetermined intervals ranging from every 1 to 8 hrs, the CI-ABGM measurements of pH, P(CO2), and P(O2) were compared with the values determined by standard intermittent blood gas analysis. The Paratrend 7 system values were individually adjusted to match ABG results when the Paratrend 7 pH differed by greater than +/-0.05 units, P(CO2) was greater than +/-5 torr (0.7 kPa), and P(O2) was greater than +/-15% of the ABG value. Significant aberrations in gas exchange defined as unanticipated events were categorized as isolated metabolic acidosis (pH <7.20), hypercapnia (P(CO2), >70 torr; 9.3 kPa), and hypoxemia (P(O2), <50 torr; 6.7 kPa). All unanticipated events were earmarked from consecutive monitoring epochs ranging from 4 to 24 hrs duration from the time of Paratrend 7 sensor insertion to the time of sensor removal. Fifteen sensors were placed into the radial artery, 34 sensors were placed into the femoral artery, and one sensor was initially placed in the radial and moved to a femoral artery location. Mean radial artery insertion duration was 35 hrs. Mean femoral artery duration was 137.2 hrs. A total of 1445 pairs of ABG results were available for comparison. After removal of individual values, which did not meet inclusion criteria, 1411 pH data pairs, 1408 P(CO2) data pairs, and 1326 P(O2) data pairs were analyzed. The bias and precision for the pH data were 0.00 and 0.04 units, respectively; for the P(CO2) data were -0.4 and 4.8 torr (-0.05 and 0.64 kPa), respectively; and for the P(O2) data 1.0 and 25 torr (0.1 and 3.3 kPa), respectively. Detection of unanticipated events was evenly spread across the three categories and was most commonly related to iatrogenic causes or cardiac failure. Persistent waveform dampening necessitating sensor removal was more frequently encountered in radial placement compared to femoral placement. CONCLUSIONS: The Paratrend 7 CI-ABGM is accurate within the extremes of physiologic gas exchange typically encountered in the pediatric intensive care setting. The device is capable of tracking extreme fluctuations in gas exchange with a response rate suitable for making real-time therapeutic decisions. The sensor can be recommended for insertion into a femoral artery cannula. There is a high incidence of blood pressure waveform dampening encountered in radial artery use.

HIV-associated wasting in the era of HAART: a practice-based approach to diagnosis and treatment.

Wasting remains an important, yet often overlooked, condition in HIV-infected patients receiving HAART. Successful office-based management depends on early diagnosis by bioelectric impedance analysis and on a multifaceted approach to treatment. Immediate goals include controlling viral load, correcting any immediate causes of wasting, and improving nutritional intake. Should wasting persist despite these measures, various therapies may be initiated. These include testosterone replacement therapy in hypogonadal patients, recombinant human growth hormone, anabolic steroids, progressive resistance exercise, and experimental therapies. Early treatment of HIV-associated wasting restores body cell mass, improves quality of life, and reduces the frequency of opportunistic infections and hospitalizations.

Evaluating the frequency rate of hypomagnesemia in critically ill pediatric patients by using multiple regression analysis and a computer-based neural network.

OBJECTIVES: To determine the frequency rate of hypomagnesemia in patients admitted to the pediatric intensive care unit (ICU), and to identify subsets of patients (grouped by disease) who are at greatest risk of hypomagnesemia. We also compared a neural network model with multiple regression analysis to identify independent variables that would correlate with hypomagnesemia and to predict serum magnesium values in critically ill pediatric patients overall. DESIGN: Prospective, multicenter study. SETTING: Tertiary level medical/surgical pediatric ICUs. PATIENTS: Data were obtained at admission to the pediatric ICU for 463 patients from newborn to 18 yrs old who were admitted with a variety of surgical and nonsurgical conditions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total serum magnesium values were obtained within the first 24 hrs after admission in 463 pediatric patients admitted to four pediatric ICUs. Hypomagnesemia (defined as total serum magnesium <0.75 mmol/L) was found in 51 (11%) of the 463 patients, with the highest frequency rate (72%) and lowest mean serum magnesium level (0.66 +/- 0.17 mmol/L) in patients admitted after surgery with extensive osseous involvement (spinal fusion and craniofacial reconstruction). To determine whether hypomagnesemia could be predicted on the basis of other laboratory and clinical criteria, multiple regression analysis was performed and showed age, weight, and albumin levels weakly associated (r2 = .14, p < .001) with magnesium levels within the different diagnostic groups. These data were used to produce a mathematical model able to predict magnesium levels within 5% of the actual values in 23% of patients. A neural network was also created to compare its predictive capabilities to those of the multiple regression model. Once trained on a random subset (85%) of the patient population, the neural network was able to predict magnesium levels to within 5% of actual values for 88% of the remaining 15% of patients, comparing favorably with the predictions derived from the multiple regression model. CONCLUSIONS: Hypomagnesemia is not uncommon (11%) in critically ill pediatric patients, but is very common (72%) in patients admitted after surgery for spinal fusion or craniofacial reconstruction. Patients who undergo surgery for correction of scoliosis and craniofacial anomalies should have serum magnesium levels monitored closely after surgery. In other patients, a neural network or multiple regression model could help predict which patients would be at risk of developing hypomagnesemia, thereby focusing testing on patients likely to benefit from such testing.

Epoetin alfa therapy for anaemia in HIV-infected patients: impact on quality of life.

To evaluate the effect of epoetin alfa on the quality of life (QOL) of HIV-infected patients in the community setting, 221 anaemic (haemoglobin < or = 11 g/dl) HIV-positive patients from community-based treatment centres and physicians' offices were treated with epoetin alfa (100-300 units/kg subcutaneously 3 times a week) in a 4-month, open-label, non-randomized, phase IV trial. Epoetin alfa therapy significantly (P<0.01) increased and maintained haemoglobin levels (mean increase=2.5 g/dl; n=207); the improvement in haemoglobin levels was independent of changes in CD4+ cell counts. Transfusion requirements were also significantly reduced from 20% to 5% of patients (P<0.01). Mean total QOL score measured by the Functional Assessment of HIV Infection (FAHI) scale and Physical Well-Being subscale score improved significantly (P<0.05). QOL improvements associated with increases in haemoglobin were independent of changes in CD4+ counts and baseline anaemia severity. Adverse events observed during epoetin alfa therapy were consistent with HIV disease and not likely due to the drug. Epoetin alfa therapy should be considered a treatment option for HIV-infected patients with mild-to-moderate anaemia.

Low-dose daily subcutaneous interleukin-2 in combination with highly active antiretroviral therapy in HIV+ patients: a randomized controlled trial.

PURPOSE: Previous studies with intermittent interleukin-2 (IL-2) therapy using intermediate and high levels of IL-2 have demonstrated significant increases in the CD4 + T cell count in HIV-infected patients. Intermittent regimens are amenable to outpatient use, but severe adverse events are frequently experienced with intermediate- and high-dose levels of IL-2. Therefore in this study, the effect of daily, subcutaneous low-dose IL-2 therapy on safety and immunological endpoints was investigated to determine whether immunological benefit could be achieved without toxicity in HIV-infected patients also receiving highly active antiretroviral therapy (HAART). METHOD: A total of 115 patients were enrolled in the trial. Fifty-six asymptomatic HIV-infected patients who had CD4 + T cell counts less than 300 cells/microL at screening and a stable HIV viral load received low-dose IL-2 (1.2 million IU [MIU]/m 2 beginning dose) once daily in conjunction with HAART (IL-2 group). Fifty-nine patients received HAART alone (control group). RESULTS: A dramatic effect of IL-2 on the natural killer (NK) cell population was observed with mean increases of 156 cells/microL in the IL-2 group compared to 19.93 cells/microL in the control group (p <.001). Additionally, IL-2-treated patients experienced a statistically significant increase in the mean percentage of CD4 + T cells (3.52% increase) when compared to control patients (1.33% increase) (p <.001). The expanded CD4 + T cell population was primarily of the naive phenotype, with mean increases of 4.53% for the IL-2 group and 0.31% for the control group (p <.001 for between-group difference). In addition, a higher proportion of IL-2-treated patients (67%) compared to control patients (33%) achieved increases of greater than 50% in the CD4+ T cell count (p =.08). Adverse events of grade 3 or grade 4 toxicity were infrequent in the current study and were substantially lower by comparison to those in studies of intermittent dose IL-2 therapy. Also, negligible changes in the HIV viral load from baseline to final measurement were observed in both groups. A trend toward a reduced number of modifications of antiretroviral therapy was apparent in the IL-2 group when compared to control patients. CONCLUSION: Daily, low-dose subcutaneous IL-2 therapy in conjunction with HAART is safe and well tolerated and is effective in expanding lymphocyte cell types including NK cells and naive T cells in individuals who have <300 CD4+ T cells.

Unaltered pulmonary capillary surface area in the presence of changing arterial resistance.

We hypothesized that capillary recruitment may not be solely dependent on extracapillary factors. To test this hypothesis, rabbits were anesthetized and placed on total cardiac bypass at a constant, physiological pulmonary blood flow. Vascular occlusion techniques were combined with measurement of the transpulmonary metabolism of an angiotensin-converting enzyme substrate, allowing the concomitant assessment of changes in segmental resistances and dynamically perfused capillary surface area. Intra-arterial serotonin infusion increased upstream pulmonary vascular resistances without affecting dynamically perfused capillary surface area. Intra-arterial isoproterenol infusion diminished serotonin-induced increased upstream resistances, also without affecting capillary surface area. These findings support the hypothesis that pulmonary capillary recruitment may not be solely dependent on extracapillary factors.

Extracorporeal whole body hyperthermia treatments for HIV infection and AIDS.

Whole body hyperthermia therapy (WBHT) is the elevation of the core body temperature to 42 degrees C. In vitro studies have confirmed that 42 degrees C is cytocidal for virally infected lymphocytes, and even more effective when heating is repeated 4 days later. The safety and efficacy of two successive sessions of WBHT (4 days apart) was evaluated in 30 patients with AIDS (not on protease inhibitors), randomized to: 1) untreated controls, 2) low temperature WBHT for 1 hour at 40 degrees C and repeated 96 hours later, and 3) high temperature WBHT for 1 hour at 42 degrees C and repeated 96 hours later. The sorbent suspension in the ThermoChem System (HemoCleanse, West Lafayette, IN) system automatically controlled blood phosphate, calcium, and other electrolyte concentrations during WBHT. In 1 year of follow-up after WBHT, there were positive effects of the therapy on frequency of AIDS defining events, Karnofsky score, and weight maintenance. However, effects on plasma HIV RNA and CD4 counts were transient. Two successive WBHT treatments were performed in four patients who were on protease inhibitor/triple drug therapy, but had suboptimal response. In follow-up for 6 months, plasma HIV RNA and CD4 improved after WBHT, and the patients remained clinically well. This WBHT may have specific advantages in patients with suboptimal response to protease inhibitor therapy.

Effectiveness of ribavirin in otherwise well infants with respiratory syncytial virus-associated respiratory failure. Pediatric Critical Study Group.

OBJECTIVE: To examine ribavirin's effectiveness in otherwise well infants with respiratory syncytial virus (RSV)-associated respiratory failure. DESIGN: Prospective multicenter cohort study. SETTING: Pediatric critical care units affiliated with the Pediatric Critical Care Study Group; 38 centers from the United States and Canada participated. PATIENTS: Infants with RSV-associated respiratory failure undergoing mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data collected included demographic information; dates of hospitalization, intensive care, and mechanical ventilation; all patient diagnoses; reason for tracheal intubation; dates of ribavirin use before and during mechanical ventilation; time in hours after intubation until ribavirin administration; Pediatric Risk of Mortality (PRISM) score; and outcome. A total of 439 patients received mechanical ventilation for RSV-associated respiratory failure; 223 were classified as previously well and met entry criteria. Ninety-one infants (41%) received ribavirin during mechanical ventilation. The PRISM scores during the initial 24 hours of intensive care and blood gas measurements before intubation were similar for patients who received ribavirin versus those who did not. Use of ribavirin during mechanical ventilation was associated with prolonged duration of mechanical ventilation (p < 0.01) in a multivariate model that controlled for patient age, gender, prematurity status, and use of ribavirin before intubation. Subgroup analysis of mechanical ventilation days for previously well patients was 5.0 +/- 4.2 in the no-ribavirin group versus 6.4 +/- 5.0 in the ribavirin group (p < 0.05) and for well premature infants was 6.3 +/- 4.9 in the no-ribavirin group versus 9.0 +/- 6.3 in the ribavirin group (p < 0.01). The mortality rates for the term and the premature groups were similar for treated and untreated patients. CONCLUSIONS: Ribavirin administration during mechanical ventilation to previously well infants with RSV infection was not associated with reductions in either mortality rates or duration of mechanical ventilation. Additional clinical effectiveness studies are required to define specific groups in which the use of aerosolized ribavirin is indicated.

Effect of whole-body hyperthermia on AIDS patients with Kaposi's sarcoma: a pilot study.

The safety and possible efficacy of extracorporeal whole-body hyperthermia (WBHT) were evaluated in the first FDA-approved feasibility study of WBHT in persons with AIDS. Six gay men, aged 20-50 years, CDC class C-3, underwent 1 h of WBHT at either 40 degrees C or 42 degrees C, employing a system that minimizes the physiological and biochemical changes that occur during WBHT. All subjects had Kaposi's sarcoma (KS), were free of opportunistic infections, and had significant elevations of plasma HIV RNA. During the treatment, there were no adverse side effects and all subjects tolerated WBHT without problems. KS lesions partially regressed immediately following WBHT in all subjects but returned to pretreatment status in five of six patients at 1 week. In subjects treated at 40 degrees C, CD4 counts decreased during the 8-week follow-up period; they remained unchanged, however, following 42 degrees C WBHT. Viral load remained unchanged following WBHT in subjects treated at 40 degrees C. Treatment at 42 degrees C resulted in an immediate reduction in HIV RNA that was not sustained at 1 week post-WBHT. We conclude that WBHT is safe in subjects with advanced HIV disease and that it may have a role in treating HIV infection. A larger controlled trial involving two treatments in less immunocompromised subjects is currently in progress to test this hypothesis.

Shedding light on the use of heat to treat HIV infections.

Considering the lack of effectiveness of current therapies to treat HIV disease, the authors present observations that provide a strong cogent argument for critically designed and meticulously performed clinical trials employing whole body hyperthermia with or without other therapeutic modalities. Only as a result of such clinical trials will it be possible to fairly evaluate the role of hyperthermia as a potential therapy for treatment of chronic HIV infection.

Determination of rebreathing oxygen consumption and derivation of oxygen delivery in intubated mongrel dogs after phlebotomy and isoproterenol infusion.

This study attempted to determine the correlation between oxygen consumption (VO2), pulmonary-capillary blood flow (QEPC), and oxygen delivery (DO2) by rebreathing and invasive techniques obtained over a range of hemoglobin concentration and cardiac output. Twenty mongrel dogs were instrumented with central arterial and venous catheters to determine DO2 by thermodilution cardiac output and standard formulas. The animals were administered isoproterenol in doses that increased DO2 and subsequently were serially phlebotomized by 30%, 40%, and 50% to decrease DO2. All animals were studied using a rebreathing technique to determine noninvasively VO2, QEPC, and DO2. Sixteen dogs completed the experimental protocol. A correlation analysis was carried out for VO2, QEPC, and DO2 obtained by the rebreathing and invasive methods. Thermodilution cardiac output increased from 3.91 +/- 1.77 L/min at baseline to 8.19 +/- 2.50 L/min during isoproterenol infusion. Hemoglobin varied from 12.21 +/- 1.26 gm% at baseline to 5.21 +/- 1.36 g% at 50% phlebotomy. Over this range of conditions, significant correlations were obtained between rebreathing VO2 and invasive VO2 (r = 0.80, p < 0.0001), rebreathing QEPC and invasive QEPC (r = 0.79, p < 0.0001), and rebreathing DO2 and invasive DO2 (r = 0.82 p < 0.0001). These data demonstrate that the rebreathing technique can be used to monitor oxygen metabolism over wide ranges of DO2.

Esophageal-aortic erosion associated with double aortic arch and tracheomalacia. Experience with 2 infants.

Patients with double aortic arch may require lengthy intubation for ventilatory support. The need for endotracheal and nasogastric intubation may be prolonged in such patients because of associated tracheomalacia. Iatrogenic tracheal or esophageal erosion with subsequent aortic fistulization is an unusual but catastrophic complication that may result from such intubation. We report the cases of 2 infants with double aortic arch and tracheomalacia who developed iatrogenic esophageal-aortic erosion. This complication was successfully managed in 1 of the infants. We conclude from our experience that the important steps in preventing this complication include 1) expediting the exclusion of upper-airway compromise in intubated infants who have a presentation characteristic of bronchospastic airway disease (hyperinflation and hypercapnia) that seems unresponsive to usual therapeutic measures; and 2) expediting the diagnosis of vascular ring in order to minimize the duration of dual tracheal and esophageal intubation. Effective management of this problem, once established, requires primary closure of the esophageal perforation, removal of the nasogastric tube, interposition of thick viable tissue between the esophagus and the aorta, and decompressive gastrostomy and feeding jejunostomy. Concomitant aortopexy may be appropriate.

Correlates of brain edema in uncontrolled IDDM.

Blood glucose, plasma sodium, bicarbonate (HCO3-), vasopressin, and hematocrit were monitored before and during treatment in patients with uncontrolled insulin-dependent diabetes mellitus (IDDM). These parameters were correlated with simultaneous serial cranial computed tomography readings of brain edema. Six of seven patients had positive computed tomography readings for brain edema on admission. Initial brain edema correlated directly with blood glucose (r = 0.79, P = 0.033) and inversely with HCO3- (r = -0.76, P = 0.047). At 6 h, brain edema still correlated with acidosis (HCO3-; r = -0.79, P = 0.033) but no longer with blood glucose. At that time, however, brain edema correlated with the rate of change in blood glucose (r = 0.915, P = 0.005). Results of interactive stepwise regression analysis suggest that the change in the calculated effective plasma osmolality plays a predominant role in the progression of brain edema during therapy (r = 0.995, P less than 0.001). Thus, although hyperglycemia and acidosis probably predispose to diabetic brain edema, osmotic factors may be major predictors of its evolution. No relationships were detected between brain edema and initiation of insulin therapy, plasma vasopressin, or changes in hematocrit. The factors responsible for initial brain edema and its progression, statistically identified in this study, require reassessment of common theories that attribute brain edema exclusively to therapy.

Osmoregulation of vasopressin in diabetic ketoacidosis.

Osmoregulation of arginine vasopressin (AVP) is altered in diabetic ketoacidosis (DKA). With hyperglycemia, the AVP-plasma sodium (PNa) curve is displaced to the left, whereas the AVP-osmolality (Posm) curve is displaced to the right. The shift in the Na curve is explained by either resetting of the Na set point or by glucose acting as a nonpermeable solute, substituting for Na. Conversely, putative unmeasured solutes that, like urea, fail to affect AVP have been postulated to account for the right shift in the AVP-Posm curve. Therefore the respective roles of Posm = sigma [Xi] and plasma tonicity (Pton = sigma [sigmaiXi]), i.e., the sum of concentrations of all solutes [Xi] corrected (Pton) or not (Posm) for their relative cell permeability (sigma i), were studied in DKA. Indeed, Posm = sigma [Xi] exceeds Pton = sigma [sigma iXi] in DKA, since sigma i less than 1 for glucose. Potential determinants of AVP release (Posm, Pton, and PNa) were monitored in 7 patients with DKA. Conventional correlation analysis and two-dimensional (2D) graphs reproduced the paradox of an opposite shift in PNa and Posm set points for AVP release. However, by using the concept of tonicity instead of osmolality, 3D plots instead of 2D graphs, and multiple regressions instead of correlations, the AVP-PNa and AVP-Pton curves did not appear displaced. The concept of tonicity resolved the paradox of both osmolality and Na thresholds reset in opposite directions. Indeed, in states where a solute like glucose (with sigma less than 1) contributes substantially to plasma osmolality, Posm measured in vitro by the osmometer greatly exceeds Pton perceived in vivo by the osmoreceptor.

Noninvasive determination of effective (nonshunted) pulmonary blood flow in normal and injured lungs.

PEEP is utilized in acute respiratory failure to decrease intrapulmonary shunting and improve oxygenation. Despite these beneficial effects, PEEP may adversely affect cardiac output, thus reducing oxygen delivery. To monitor some of the cardiopulmonary effects of PEEP, we utilized a noninvasive rebreathing technique to measure effective (nonshunted) pulmonary blood flow (Qepr) and compared the results to those measured by thermodilution (Qepi) in normal and oleic acid-injured canine lungs. Qepr was highly correlated with Qepi (r = .92, r2 = .85, p less than .001) despite large variations in PEEP before lung injury (0 to 15 cm H2O) and after lung injury (0 to 20 cm H2O). This close correlation was found even with wide ranges in cardiac output (1.01 to 6.45 L/min) and intrapulmonary shunt fractions (0.03 to 0.67). This technique may prove valuable as a noninvasive method by which to monitor and adjust PEEP therapy in patients with acute lung injury.

Poisoning.

Knowledge of the toxicologic nature of ingested substances provides a proper framework for general and specific therapies best suited to meet the needs of the patient. Monitoring and direct observation provided in the PICU can aid proper therapy for many intoxicants. Good supportive care coupled with specific pharmacotherapy will provide the best chance for a successful outcome.