Given that the leading clinical conditions associated with Acute kidney injury (AKI), namely, sepsis, major surgery, heart failure and hypovolemia, are all associated with shock, it is tempting to attribute all AKI to ischemia on the basis of macro-hemodynamic changes. However, an increasing body of evidence has suggested that in many patients, AKI can occur in the absence of overt signs of global renal hypoperfusion. Indeed, sepsis-induced AKI can occur in the setting of normal or even increased renal blood flow. Accordingly, renal injury may not be entirely explained solely on the basis of the classic paradigm of hypoperfusion, and thus other mechanisms must come into play. Herein, we put forward a “unifying theory” to explain the interplay between inflammation and oxidative stress, microvascular dysfunction, and the adaptive response of the tubular epithelial cell to the septic insult. We propose that this response is mostly adaptive in origin, that it is driven by mitochondria and that it ultimately results in and explains the clinical phenotype of sepsis induced AKI.

Ischemic acute renal failure leads to down regulation of pulmonary ENaC, Na,K-ATPase and aquaporin-5, but not aquaporin-1. Since bilateral nephrectomy but not single kidney I/R injury also leads to lung changes, these changes are likely mediated by systemic effects of acute renal failure (ARF), such as "uremic toxins," rather than reperfusion products. These changes may modulate lung dysfunction, susceptibility to lung injury, or both.

To investigate whether respiratory acidosis modulates ventilator-induced lung injury (VILI), we perfused (constant flow) 21 isolated sets of normal rabbit lungs, ventilated them for 20 min (pressure controlled ventilation [PCV] = 15 cm H(2)O) (Baseline) with an inspired CO(2) fraction adjusted for the partial pressure of CO(2) in the perfusate (PCO(2) approximately equal to 40 mm Hg), and then randomized them into three groups. Group A (control: n = 7) was ventilated with PCV = 15 cm H(2)O for three consecutive 20-min periods (T1, T2, T3). In Group B (high PCV/normocapnia; n = 7), PCV was given at 20 (T1), 25 (T2), and 30 (T3) cm H(2)O. The targeted PCO(2) was 40 mm Hg in Groups A and B. Group C (high PCV/hypercapnia; n = 7) was ventilated in the same way as Group B, but the targeted PCO(2) was approximately equal to 70 to 100 mm Hg. The changes (from Baseline to T3) in weight gain (Delta WG: g) and in the ultrafiltration coefficient (Delta K(f) = gr/min/ cm H(2)O/100g) and the protein and hemoglobin concentrations in bronchoalveolar lavage fluid (BALF) were used to assess injury. Group B experienced a significantly greater Delta WG (14.85 +/- 5.49 [mean +/- SEM] g) and Delta K(f) (1.40 +/- 0.49 g/min/cm H(2)O/100 g) than did either Group A (Delta WG = 0.70 +/- 0.43; Delta K(f) = 0.01 +/- 0.03) or Group C (Delta WG = 5.27 +/- 2.03 g; Delta K(f) = 0.25 +/- 0.12 g/min/cm H(2)O/ 100 g). BALF protein and hemoglobin concentrations (g/L) were higher in Group B (11.98 +/- 3.78 g/L and 1.82 +/- 0.40 g/L, respectively) than in Group A (2.92 +/- 0.75 g/L and 0.38 +/- 0.15 g/L) or Group C (5.71 +/- 1.88 g/L and 1.19 +/- 0.32 g/L). We conclude that respiratory acidosis decreases the severity of VILI in this model.

To determine if decreased respiratory frequency (ventilatory rate) improves indices of lung damage, 17 sets of isolated, perfused rabbit lungs were ventilated with a peak static airway pressure of 30 cm H(2)O. All lungs were randomized to one of three frequency/peak pulmonary artery pressure combinations: F20P35 (n = 6): ventilatory frequency, 20 breaths/min, and peak pulmonary artery pressure, 35 mm Hg; F3P35 (n = 6), ventilatory frequency, 3 breaths/min, and peak pulmonary artery pressure of 35 mm Hg; or F20P20 (n = 5), ventilatory frequency, 20 breaths/min, and peak pulmonary artery pressure, 20 mm Hg. Mean airway pressure and tidal volume were matched between groups. Mean pulmonary artery pressure and vascular flow were matched between groups F20P35 and F3P35. The F20P35 group showed at least a 4.5-fold greater mean weight gain and a 3-fold greater mean incidence of perivascular hemorrhage than did the comparison groups, all p

Objective-To examine whether the historical link between tuberculosis and poverty still exists.Design-Retrospective study examining the notifications of all forms of tuberculosis by council ward over a six year period and correlating this with four indices of poverty; council housing, free school meals, the Townsend overall deprivation index, and the Jarman index.Setting-The 33 electoral wards of the city of Liverpool.Subjects-344 residents of Liverpool with tuberculosis.Results-The rate of tuberculosis was correlated with all measures of poverty, the strongest correlation being with the Jarman index p

We conclude that RM transiently but profoundly depressed cardiac output in three models of acute lung injury. The results imply that a lung recruiting maneuver should be used with caution, especially when using sustained inflation in the setting of pneumonia.

To investigate whether the magnitude of blood flow contributes to ventilator-induced lung injury, 14 sets of isolated rabbit lungs were randomized for perfusion at either 300 (Group A: n = 7) or 900 ml/ min (Group B: n = 7) while ventilated with 30 cm H2O peak static pressure. Control lungs (Group C: n = 7) were ventilated with lower peak static pressure (15 cm H2O) and perfused at 500 ml/min. Weight gain, changes in the ultrafiltration coefficient (DeltaKf) and lung static compliance (CL), and extent of hemorrhage (scored by histology) were compared. Group B had a larger decrease in CL (-13 +/- 11%) than Groups A (2 +/- 6%) and C (5 +/- 5%) (p < 0.05). Group B had more hemorrhage and gained more weight (16.2 +/- 9.5 g) than Groups A (8.7 +/- 3.4 g) and C (1.6 +/- 1.0 g) (p < 0.05 for each pairwise comparison between groups). Finally, Kf (g . min-1 . cm H2O-1 . 100 g-1) increased the most in Group B (DeltaKf = 0.26 +/- 0. 20 versus 0.17 +/- 0.10 in Group A and 0.05 +/- 0.04 in Group C; p < 0.05 for B versus C). We conclude that the intensity of lung perfusion contributes to ventilator- induced lung injury in this model.

Recent technical advances in combinatorial chemistry, genomics, and proteomics have made available large databases of biological and chemical information that have the potential to dramatically improve our understanding of cancer biology at the molecular level. Such an understanding of cancer biology could have a substantial impact on how we detect, diagnose, and manage cancer cases in the clinical setting. One of the biggest challenges facing clinical oncologists is how to extract clinically useful knowledge from the overwhelming amount of raw molecular data that are currently available. In this paper, we discuss how the exploratory data analysis techniques of machine learning and high-dimensional visualization can be applied to extract clinically useful knowledge from a heterogeneous assortment of molecular data. After an introductory overview of machine learning and visualization techniques, we describe two proprietary algorithms (PURS and RadViz) that we have found to be useful in the exploratory analysis of large biological data sets. We next illustrate, by way of three examples, the applicability of these techniques to cancer detection, diagnosis, and management using three very different types of molecular data. We first discuss the use of our exploratory analysis techniques on proteomic mass spectroscopy data for the detection of ovarian cancer. Next, we discuss the diagnostic use of these techniques on gene expression data to differentiate between squamous and adenocarcinoma of the lung. Finally, we illustrate the use of such techniques in selecting from a database of chemical compounds those most effective in managing patients with melanoma versus leukemia.