The symptoms in Idiopathic Adult Hydrocephalus Syndrome (IAHS) – gait disturbance, incontinence, and cognitive deficit – correlate anatomically to neuronal dysfunction in periventricular white matter. The pathophysiology is considered to include a cerebrospinal fluid (CSF) hydrodynamic disturbance, including pressure oscillations (“B waves”), in combination with cerebrovascular disease. IAHS and Subcortical Arteriosclerotic Encephalopathy (SAE) show clinical similarities, which constitutes a diagnostic problem. The aim of this thesis was to investigate biochemical markers in CSF, possibly related to the pathophysiology, and their usefulness in diagnosis, to investigate the effect of ICP changes on glucose supply and metabolism in periventricular deep white matter, and to present criteria for objective, computerised methods for evaluating the content of B waves in an intracranial pressure (ICP) registration. CSF samples from 62 IAHS patients, 26 SAE patients, and 23 controls were analysed for sulfatide, total-tau (T-tau) hyperphosphorylated tau (P-tau), neurofilament protein light (NFL), and beta-amyloid-42 (Aß42). In ten IAHS patients, recordings of ICP, brain tissue oxygen tension (PtiO2), and samplings of brain extracellular fluid from periventricular white matter by way of microdialysis were performed, at rest and during a CSF infusion and tap test. Microdialysis samples were analysed for glucose, lactate, pyruvate, glutamate, glycerol, and urea. Patterns before and after spinal tap were analysed and changes from increasing ICP during the infusion test were described. The long term ICP registration was used to evaluate two computerised methods according to optimal amplitude threshold, monitoring time, and correlation to the manual visual method. In CSF, NFL was elevated in both IAHS and SAE patients, reflecting the axonal damage. In a multinominal logistic regression model, the combined pattern of high NFL, low P-tau and low Aß42 in CSF was shown to be highly predictive in distinguishing between IAHS, SAE and controls. Analysis of microdialysis samples for glucose, lactate, and pyruvate showed, in combination with PtiO2, a pattern of low-grade ischemia. After the spinal tap of CSF, the pattern changed, indicating increased glucose metabolic rate. During the infusion test, there were prompt decreases in the microdialysis values of glucose, lactate and pyruvate during ICP increase, but no sign of hypoxia. The values normalised immediately when ICP was lowered, indicating that the infusion test is not causing damage. One of the computerised methods, with an amplitude threshold set to 1 mm Hg, was shown robust in evaluating B wave content in an ICP registration. At least 5 hours registration time was needed. The highly predictive pattern of biochemical markers in CSF indicates a possibility of identifying simple tests in diagnosing and selecting patients for surgical treatment. The results of microdialysis and PtiO2 indicate low-grade ischemia in the periventricular white matter, which is ameliorated from CSF removal, and that glucose supply and metabolism are sensitive to short-term ICP elevations, thus proposing a link between ICP oscillations and symptoms from neuronal disturbance. A computerised method for evaluation of B waves is a prerequisite for evaluating the impact of pressure oscillations in the pathophysiology of IAHS.

An individual who has sustained either irreversible cessation of circulatory and respiratory functions, or irreversible cessation of all functions of the entire brain, including the brain stem is dead. Brain death is currently the legal definition of death in many countries. Many people confuse brain death with vegetative states. Patients in a vegetative state are unaware of themselves or their environment. Both patients with brain death and those in a vegetative state are unconscious following severe brain injury. Unlike the brain death, vegetative patient¡¦s vital vegetative functions, such as cardiac action, respiration, and maintenance of blood pressure are preserved. The rostral ventrolateral medulla (RVLM) is the origin of a ¡§life-and-death¡¨ signal identified from systemic arterial blood pressure spectrum and intimately related to brain death. Based on the animal models of brain death, the observations that the power density of the vasomotor components of SAP signals undergoes both augmentation and reduction during the progression towards death strongly suggest that both ¡¥¡¥pro-life¡¦¡¦ and ¡¥¡¥pro-death¡¦¡¦ programs are present in the RVLM. A number of those ¡¥¡¥pro-life¡¦¡¦ and ¡¥¡¥pro-death¡¦¡¦ programs in the RVLM has now been identified along with their cellular and molecular mechanisms. As the neural substrate that is intimately related to brain death, one unresolved question is whether the proteome expressed in RVLM is unique. To address the issue, we used the cerebral cortex, which is defunct under persistent vegetative state for comparison. 2-DE electrophoresis, MALTI-TOF MS and peptide mass fingerprinting were used for investigation the proteomic difference between the rat RVLM and cerebral cortex. Quantitative analysis on silver-stained 2-DE electrophoresis gels revealed highly comparable distribution patterns of these protein spots for both brain regions, with 85.9 ¡Ó 2.3 % of protein spots from RVLM matched those from cerebral cortex. According to the protein function, these proteins were classed into binding activity, chaperone, antioxidant, oxidoreductase, ubiquitin- proteasome system, cell cycle, catalytic activity, glycolysis, tricarboxylic acid cycle, electron transport chain, endocytosis and exocytosis, structural molecular function, apoptosis, transport, differentiation and neurogenesis, protein biosynthesis, cell junction, and others. We found that a group of antioxidant proteins, including members of the peroxiredoxin (Prx) family (Prx-1, Prx-2, Prx-5, and Prx-6), thioredoxin and mitochondrial manganese superoxide dismutase exhibited significantly higher protein and mRNA expression levels in RVLM when compared to cerebral cortex. Tissue oxygen, ATP contents and ATP synthase subunits alpha and beta in RVLM were also significantly elevated. On the other hand, protein and mRNA levels of members of the ubiquitin-proteasome system, including proteasome subunit alpha type-1, ubiquitin, uniquitin-conjugating enzyme E2 N, ubiquitin carboxyl-terminal hydrolase isozyme L1 and L3, were comparable in both brain regions. The presence of higher levels of tissue oxygen and ATP synthase subunits in RVLM, leading to augmented ATP production, provides a cellular safeguard mechanism to reduce the possibility of irreversible reduction in intracellular ATP contents that precipitate brain death. By manifesting an augmented tissue oxygen and metabolic energy production, RVLM is more prone to oxidative stress. We conclude that a significantly elevated level of antioxidant proteins and mRNA in RVLM is consistent with the exhibition of higher tissue oxygen tension and metabolic energy production in this neural substrate, which together constitute a safeguard mechanism against brain death.

Development of a Tool for Pressure Ulcer Risk Assessment and Preventive Interventions in Ancillary Services Patients Monica S. Messer Abstract The incidence of nosocomial pressure ulcers has increased 70 percent in U.S. hospitals over the past 15 years despite implementation of preventive guidelines and the wide-spread use of validated risk assessment tools. Most preventive efforts have been focused primarily on patients who are bed-ridden or immobile for extended periods. What has not been well studied or identified is the risk for pressure injury to patients undergoing diagnostic procedures in hospital ancillary units where extrinsic risk factors such as high interface pressures on procedure tables and friction and shear from positioning and transport can greatly magnify the effect of patient-specific intrinsic risk factors which might not otherwise put these patients at high risk on an inpatient unit. The purpose of this study was to develop a risk assessment tool designed explicitly to quantify the combination of these intrinsic and extrinsic risk factors in individual patients undergoing ancillary services procedures, and to identify targeted preventive interventions based on the individual level of risk. Empirically and theoretically-derived risk factors for the tool were tested in a nation-wide hospital database of over 6 million patient discharge records using bivariate and multivariate analysis to identify significant predictors of pressure ulcer outcomes. The statistically significant factors emerging were then used to develop the risk assessment scale. These predictors included; advanced age, diabetes, human immunodeficiency virus infection, sepsis, and fever. The scale was tested for internal validity using the split-sample cross-validation method, and for accuracy using the area under the Receiver Operating Characteristics curve. The optimum score cut point was identified to provide a predictive accuracy of 71 percent. Interventions for the tool were identified from national clinical practice guidelines and aligned in sets based on patient levels of risk identified by the scoring portion of the tool. The entire tool was evaluated for content validity by a panel of five international nurse experts in pressure ulcer prevention and tool development. The content validity index calculated from their ratings was .91 indicating excellent agreement on content validity.

No description available.

No description available.

The objective of this study was to evaluate the relationship between tissue oxygen saturation (StO2) and oxygen delivery index (DO2I). Oxygen delivery index is product of two factors arterial oxygen content (CaO2) and cardiac index (CI). In this study the relationship between DO2I and StO2 was evaluated by manipulating both of these factors independently. In phase one of the study, CaO2 was altered by manipulating the fractional inspired oxygen (FiO2) concentration. Anesthetized dogs were evaluated at both high (0.40 and 0.95) and low (0.15 and 0.10) FiO2 sequences. In phase two of the study, CI was altered by manipulating the volemic state. Anesthetized dogs were evaluated at hypovolemic, normovolemic and hypervolemic states. In each phase dogs were instrumented for thermodilution cardiac index (CI) and sartorius muscle StO2. Data collected included hemoglobin concentration, heart rate (HR), MAP, CI, StO2. Arterial oxygen content and DO2I were calculated at each time point. Data analysis included Pearson's correlation and mixed model ANOVA (p < 0.05). In both phases one (r = 0.97; p = 0.0013) and two (r = 0.97; p = 0.005) there was a strong correlation between StO2 and DO2I. Under the conditions of this study, there was a strong correlation between StO2 and DO2I, suggesting that StO2 may be used to estimate the adequacy of oxygen delivery in dogs. / Master of Science

Background and aims: Unrecognized intestinal mucosal ischemia in severely ill patients may trigger development of multiple organ failure. Such ischemia can be evaluated by intraluminal tonometry reflecting mucosal PCO2 and intramucosal pH (pHi). The aims were to develop an apparatus for continuous saline tonometry (CST), to analyse circulatory control mechanisms during intestinal hypoperfusion and to evaluate the effect of dopexamine on intestinal circulation. Methods: A modified standard tonometry catheter was integrated in a closed system with circulating saline. By measuring saline PCO2 in a measurement unit pHi could be calculated. This novel system was tested in vitro and in vivo. In a porcine study, CST was evaluated against standard saline tonometry, tissue oxygenation (PO2 TISSUE), jejunal mucosal perfusion (laser doppler flowmetry; LDF) and mesenteric net lactate flux during graded reductions of superior mesenteric arterial pressure (PSMA). Local control mechanisms for maintenance of intestinal oxygenation were analysed. Effects of dopexamine on the intestinal vascular bed were explored. Mucosal lactate production was assessed by microdialysis. Results: CST measured accurate PCO2 values and changes in pHi during restricted intestinal circulation and at reperfusion. Local control mechanisms were insufficient at a PSMA of 30 mmHg, pHi was reduced to 7.10 and intestinal net lactate production was demonstrated. Absence of anaerobic intestinal metabolism was verified at PSMA ≥ 50 mmHg, pHi ≥ 7.22 and a PCO2 gap ≤ 15.8 mmHg. Dopexamine induced negative regional metabolic effects at the lowest PSMA, as expressed by decreased PO2 TISSUE and pHi, increased PCO2 gap and intestinal net lactate production. Conclusions: CST reflected changes in pHi, induced by intestinal hypoperfusion and at reperfusion. Levels of PSMA, pHi and PCO2 gap as indicators of aerobic conditions were defined. Dopexamine induced a decrease of PO2 TISSUE and pHi as well as an increase in lactate flux at the lowest PSMA level.

Background and aims: Lung recruitment maneuvers (brief episodes of high airway pressure) are a modern treatment alternative to achieve open lung conditions under mechanical ventilation of patients with acute lung injury. It is well known that positive pressure ventilation with high airway pressures cause negative circulatory effects, and that the effects on regional vascular beds can be even more pronounced than the systemic effects. Hypoperfusion of the mesenteric vascular bed can lead to tissue ischemia and local inflammation. This intestinal inflammation has been associated with subsequent development of multiple organ dysfunction syndrome, a syndrome that still carries a high mortality and is a leading cause of death for intensive care patients. The aim of this thesis was therefore to investigate whether lung recruitment maneuvers would cause negative effects on mesenteric circulation, oxygenation or metabolism. Methods and results: In an initial study on ten patients with acute lung injury, we could demonstrate a trend towards a decreased gastric mucosal perfusion during three repeated lung recruitment maneuvers. To more closely examine this finding, we set up an oleic acid lung injury model in pigs, and in our second study we established that this model was devoid of inherent intestinal effects and was adequate for subsequent studies of intestinal effects of lung recrutiment maneuvers. In the acute lung injury model, we also tested the effect of an infusion of a vasodilating agent concurrent with the recruitment maneuvers, the hypothesis being that a vasodilating agent would prevent intestinal vasoconstriction and hypoperfusion. We could show that three repeated lung recruitment maneuvers induced short term negative effects on mesenteric oxygenation and metabolism, but that these findings were transient and short lasting. Further, the effects of prostacyclin were minor and opposing. These findings of relative little impact on the intestines of lung recruitment maneuvers, lead us to investigate the hypothesis that repeated recruitment maneuvers maybe could elicite a protective intestinal preconditioning response, a phenomenon previously described both in the rat and in the dog. However, in our fourth study, using both classical ischemic preconditioning with brief periods of intestinal ischemia or repeated lung recrutiment maneuvers, we could not demonstrate the phenomenon of intestinal preconditioning in the pig. Conclusions: We conclude, that from a mesenteric point of view, lung recruitment maneuvers are safe, and only induce transient and short lasting negative effects. We also conclude that the cause of the minor effects of lung recruitment maneuvers is not dependent on intestinal preconditioning.