Bakgrund: Sjuksköterskans professionella område är omvårdnad, vilket utgår ifrån ett holistiskt perspektiv där sjuksköterskan ska ta hänsyn till den vårdsökande personens fysiska samt psykiska hälsa. Samhällets och medias syn på personer med psykisk sjukdom kan påverka sjuksköterskan och eventuellt bidra till stigmatisering som kan följa med in i vårdrummet. Personer med psykisk sjukdom kan uppleva sig diskriminerade och misstrodda i kontakt med hälso- och sjukvården, vilket medför en osäkerhet och risk för att de inte söker somatisk vård. Syfte: Att beskriva sjuksköterskors upplevelser av att vårda personer med psykiska sjukdomar på somatisk avdelning. Metod: Litteraturöversikt med en induktiv ansats och kvalitativa artiklar. Resultatet baserades på sju kvalitativa artiklar som analyserades genom Fribergs femstegsmodell. Resultat: Litteraturöversiktens resultat visar att sjuksköterskan upplever sig otillräcklig i omvårdnaden av personer med psykiska sjukdomar på en somatisk avdelning. Upplevelsen av otillräcklighet delades in i otillräcklighet inom organisationen med underteman som miljö, tid och stöd samt otillräcklighet inom professionen med underteman som osäkerhet, kunskap och utbildning. Slutsats: Sjuksköterskor upplevde att om de ska ansvara för omvårdnaden för personer med psykiska sjukdomar på en somatisk avdelning så krävs rätt förutsättningar, i form av kunskap och utbildning, samt en trygg och säker vårdmiljö. / Background: The profession of nurse’s is nursing, which comes from a holistic perspective where the nurse takes both physical and psychological health in consideration. The society and medias view of people with mental illness might influence the nurse. This can eventually contribute to a stigma which can follow the nurses into the hospital wards. People with mental illness feel discriminated and mistrusted in contact with healthcare, this can bring an insecurity and a risk that they won’t seek somatic care. Aim: To describe the nurse’s experience of nursing a person with mental illness on a somatic ward. Method: Litterature review with inductive approach and qualitative articles. The results were based on seven qualitative articles who were analyzed by Friberg’s five-step-model. Results: The results of the study showed that the nurses felt insufficient while nursing people with mental illness in somatic care. The experience of insufficiency was divided into insufficiency in organization with subthemes as environment, time and support, and insufficiency in profession with subthemes as uncertainty, knowledge and education. Conclusion: Nurses experienced that if they should nursing people with mental illness they need the right conditions, in terms of knowledge and education and a safe and secure healthcare environment.

Chronic Venous Insufficiency (CVI) is characterized by chronic venous hypertension from blood pooling in the lower limbs. The resulting symptoms include leg pain, varicose veins, fatigue, venous edema, skin pigmentation, inflammation, induration, and ulceration. Reflux from incompetent venous valves is a factor in up to 94% of individuals with CVI. Current treatments of CVI include compression stockings, drug therapy, vein disabling, venous stenting, and surgical correction with varying rates of success. However, a minimally invasive correction of deep venous reflux does not currently exist. A transcatheter prosthetic venous valve has the potential to be an effective, minimally invasive treatment for deep venous reflux which could treat up to 1.4 million individuals in the United States suffering from venous ulceration and make more than 1.7 billion dollars each year. Previously developed prosthetic venous valves have had problems with competency, patency, thrombogenicity, biocompatibility, and incorrect sizing. To meet the clinical need a prosthetic valve needs to be developed which succeeds where previous valves have failed. This thesis describes the design, analysis, pre-clinical testing, and evaluation of a novel prosthetic venous valve. Design specifications for an effective prosthetic venous valve were created. Verification tests were developed and performed which demonstrated that the valve met every design specification. Finite element and computational fluid dynamics simulations were performed to analyze the valve and calculated a maximum shear rate of 2300 s-1 in the valve during the high forward flow after a Valsalva maneuver. The valve is made of a biocompatible material that has low thrombogenicity, Poly(vinyl-alcohol) cryogel. On the average, the valve allows less than 0.5 mL/min of reflux at low and high retrograde pressures even after 500,000 cycles, indicating that it will reduce the reflux of individuals with venous reflux by more than 99.4%. The valve closes in less than 0.07 seconds and allows the distal pressure to rise to an average of 7% of the equilibrium pressure 30 seconds after a simulated ankle flexion. The valve increases the outflow resistance an average of 2.3 mmHg*min/L which is much less than obstruction levels,≥ 5 mmHg*min/L. The valve can fit in a 16 French catheter and is capable of percutaneous delivery. The base of the valve is 1.5 times the diameter of the vein in which it is to be implanted to help correct orientation upon deployment. Fluid behind the valve’s leaflets is ejected with a forward flow rate of 400 mL/min, suggesting that thrombus formation will not occur at this location. A stented valve remained patent in a porcine blood flow loop for 3 hours. The valve remains competent without buckling in a constricted vein at rest. The valve can expand to fit a vein with a maximum diameter 1.4 times the valve's initial diameter with low risk of tearing or leaflet prolapse. An IACUC protocol for a 12 week study to test the valve in sheep was prepared and approved. A study to evaluate the valve in humans is proposed with endpoints that can be tested for statistical significance and compared with other treatments for CVI. A set of valves which will correct reflux in the majority of common femoral, femoral, and popliteal deep veins is proposed and a sizing guide for surgeons is provided. The minimum distance between prosthetic valves placed in the same vein segment is 13 cm. A comparison of this valve with previously developed prosthetic venous valves and recommendations for work to be performed in the future are given. The valve proposed in this work is the only valve to meet all design specification for an effective prosthetic venous valve, and therefore shows great potential to be a minimally invasive treatment for deep venous reflux.

In title 12, 22, 11 are in subscript. / Thesis (PhD)--Stellenbosch University, 2002. / ENGLISH ABSTRACT: The aim of this study was to test a synthetic protein-free surfactant preparation, LPM-l, with the same chemical composition as commercially available Exosurf (Glaxo Wellcome), but containing in addition, a sugar, trehalose (TRE). Towards this end, a study was designed to firstly test the hypothesis that the true difference in acute physiological effects between a mixture of oppe, tyloxapol, hexadecanol and trehalose (LPM-l), and Exosurf, (Oppe, tyloxapol and hexadecanol) is zero, in a surfactantdeficient animal model. A second study addressed the physiological effects of oppe, hexadecanol, tyloxapol and trehalose (LPM-l) compared to treatment with trehalose (TRE) or saline, in order to determine (1) the contribution of TRE to the mixture of oppe, hexadecanol and tyloxapol, and (2) to assess the effect of the LPM-l surfactant replacement on the epithelial lining fluid composition by means of analysing bronchoalveolar lavage fluid. Thirdly, the effects of TRE and / or calcium were studied on the surface properties of oppe suspensions, by in vitro analysis using the ring detachment method of Du Nouy The in vivo research comprised of two studies, performed in randomised controlled fashion. In the first study, 24 New Zealand White adult rabbits were randomised into 4 groups, while in the second study, 15 animals were randomised into 3 groups. In the first in vivo study, three synthetic surfactants, LPM-l, Exosurf and LPM-2, and a saline group were tested. LPM-l is a new formulation that consists ofa mixture of Df'PC, TRE, hexadecanol and tyloxapol. LPM-2 is a formulation with a composition equivalent to that of commercially available Exosurf, prepared on site. In both studies animals were subjected to repeated lavage with large volumes of warm saline (25 ml/kg) in order to establish surfactant deficiency and acute lung injury. Five minutes after the last lavage, vehicle, i.e. surfactants LPM-l, Exosurf, or LPM-2, or saline, in the first in vivo study, and LPM-l, TRE or saline in the second in vivo study, was instilled, and the course of the animals followed over the next 3 hours. Ventilator settings were standardized before and after lavage. The effects of surfactant treatment on gas exchange (arterial Pa02, oxygenation index (Ol), arterial-alveolar oxygen (a/A) ratio), percentage calculated shunt, and total dynamic respiratory compliance (CRSdyn), and histopathological changes were compared with changes in saline treated controls. Arterial blood gases in 100% oxygen and CRSdynwere measured before and after lavage, at 15 minute intervals for the first 30 min, then at 60, 90, 120, and 180 min after vehicle instillation. Oxygenation improved to a similar extent after LPM-l and Exosurf instillation, surpassing that of LPM-2 or saline. Overall, intratracheal instillation of both Exosurf and LPM-l, rapidly improved the gas exchange and reduced the intrapulmonary shunt, but did not restore the lung to its pre-lavage condition. From the 2nd in vivo study it was evident that trehalose-only, was inefficient as a lung surfactant, failing to improve oxygenation indices or the calculated percentage shunt, or influencing respiratory compliance. The addition of the sugar, trehalose (TRE), to the on-site 'Exosurf mixture (LPM-2) brought the activity of the resultant LPM-l to the same level as that of commercial Exosurf, but failed to raise the activity above that of Exosurf. These physiological improvements were sustained for up to 3 hours. Saline-treated animals had no improvement in gas exchange despite management with variable PIP (to maintain a tidal volume of -1 0 ml / kg) and constant PEEP of 5 cm H20. In-vitro results, obtained by the Ou Nouy tensiometer, showed higher mean ordinate surface tension values for the OPPC-only and DPPC + TRE mixtures, and the slopes of their respective graphs smaller in magnitude than those of the other formulations, suggesting that these formulations had less surface tension-lowering capability than the other surfactants. At 20°C (20 mg / ml DPPC-surfactants) the mean ordinate values of OPPC and OPPC + TRE, 70.13 and 69.47 dyne / cm, respectively, were not significantly different from each other. The mean ordinate values of LPM-l and the formulation containing OPPC + TRE + tyloxapol + CaCh were lower, but similar, as were the values of LPM-2 (on-site Exosurf) and LPM-2 + CaCho Thus, three internally homogeneous subgroups could be identified which differed significantly, namely: DPPC and DPPC + TRE, LPM-2 and LPM-2 + CaCh, and DPPC + TRE + tyloxapol + CaCh and LPM-l. Similar conclusions apply to the ordinate values of the surfactants at 37°C, and to the mean slope values at 20°C, with the exception that the subgroups, LPM-2 and LPM-2 + CaCh, and LPM-l and OPPC + TRE + tyloxapol + CaCh are not so clearly separated. A similar analysis of mean slope values was performed. Here too a significant difference between substances was found, OPPC alone or in combination with TRE, again being significantly different from the other surfactants. The most prominent light microscopy findings of the lungs of animals included general lymphatic dilatation, congestion and lung polymorphonuclear infiltration, with no difference between study groups. Hyaline membranes were present in all surfactant groups, but significantly more so in the saline treated group. In the first in vivo study, the presence of neutrophils in the lung interstitiwn as well as alveoli, was a common finding in all of the study groups towards the end of the study protocol. A significant increase in the BAL-fluid neutrophil count occurred in all animals, concurrent with a significant decrease in the BAL macrophage count. No significant change occurred in the peripheral neutrophil count during the 3-hour study, suggesting recruitment of neutrophils from storage pools. Treatment with synthetic surfactant (LPM -1) did not have a significant effect on modifying the inflammatory response, since there was no significant difference in the BAL-derived cell counts between the LPM-1 and -saline groups. Epithelial damage was a consistent finding in all groups. The damage was more evident by electron microscopy examination and included hydropic changes, most readily observed in the mitochondria. The airspaces of study subjects showed the presence of oedema fluid. This luminal oedema appeared to be more prominent in the control group and LPM-2 (on site 'Exosurf') group. Organellar debris, probably originating from lysis of epithelial cells, was present, despite treatment with synthetic surfactant. The electron microscopical appearance of the epithelial-lined substance ("hyaline membranes") in the present study showed a marked variability within groups as well as within the same case. The majority of cases showed a mix of membrane types with both granular and fibrillar materials present within the same membrane. In some cases there were layering of the membranes into distinct bands. The instillation of LPM-l resulted in the formation of a slightly different type of epithelial lining fluid after lavage, when compared to the prelavage composition. The most pronounced changes occurred within the fatty acids, whilst the phosphatidylcholine values remained unchanged. Palmitic acid concentrations (C16:0) increased significantly, suggesting enrichment of the epithelial lining fluid after instillation of LPM-l. This increase in C16:0 was concurrent with significant decreases in the percentage C16:1, C18:0, and C18:2. In contrast to previous studies, we describe higher levels for phosphatidyldimethylethanolarnine (PEA). An explanation may be that the lipid identified as PEA, was in fact partly phosphatidylglycerol (PG)-a lipid whose accurate identification was precluded for technical reasons. After surfactant instillation, the PC/SM ratio, a reflection of the lecithin / sphingomyelin (LIS), decreased significantly in the TRE-group between the first and final lavage, but remained statistically unchanged in the animals treated with LPM-l or saline. The change in ratio was mainly accounted for by a decrease in BAL-fluid PC content together with a rise in SM content. A poor correlation existed between the BAL-derived PC/SM ratio and indices reflecting oxygenation status (a/A ratio, Ol), as well as the CRSdynat the time of the final lavage. In conclusion, the primary hypothesis was accepted, LPM-l performed similarly to Exosurf in vivo, improving oxygenation, but not CRSdyn.None was clearly superior to the other. Some questions remain. The reason why LPM-l (LPM-2 + TRE) did not behave in a superior manner, in vivo, to Exosurf, is partly unclear. This finding was somewhat surprising since the chemical composition of Exosurf and LPM-2 did not differ, and the addition of TRE to LPM-2 (on-site Exosurf), did improve the in vivo activity of the resultant LPM-l, above that of LPM-2. A possible explanation for observed differences in performance include methodological issues, i.e. the preparation of the on-site formulations, especially that of LPM-2 (on-site Exosurf), may differ from the way in which true commercial Exosurf is prepared. / AFRIKAANSE OPSOMMING: Die doel van die studie was om 'n sintetiese proteïn vrye surfaktant te ontwikkel en die produk te vergelyk met 'n kunsmatige surfaktant reeds in kliniese gebruik. Die bekende uit die literatuur en die onbekende van die produk wat evalueer sou word, lei op tot die samestelling van die nul hipotese van die PhD naamlik dat geen verskil in longfunksie sou gewys word tussen die toetsproduk en reeds gebruikte kommersiële surfaktant nie. Die hipotese was dat 'n suiker (trehalose), in kombinasie met Dipalmitoiel fosfatidielcholine (DPPC), gaswisseling en longfunksies sal verbeter vir 'n long met 'n lae surfaktant konsentrasie. Vir die studie is jong volwasse wit New Zealand konyne gebruik en is hulle met 'n gestandaardiseerde en menslike manier gebruik in eksperimentele werk. Die diere is onder intraveneuse narkose geplaas en verskillende kardiovaskulêre en pulmonologiese aspekte is gemeet. Die long surfaktant is uitgewas deur middel van fisiologiese soutoplossing wat tot liggaam temperatuur verhit is en daarna is die diere prospektief gerandomiseer tot eksperimentele groepe. Met vooraf bepaalde tydsintervalle is die fisiologiese metings herhaal en was die metings toegespits daarop om longmeganiese funksie en gasoordrag vermoë te evalueer. Lig mikroskopiese en elektron mikroskopiese studies is ook op die longe gedoen en verder is brongoalveolêre vloeistof ook ontleed. Die groepe met ondersoek was: I. oppe, heksadekanol, tyloxapol en trehalose (LPM-I). 2. oppe, heksadekanol, tyloxapol (LPM-2 :. LPM-I sonder trehalose). Hierdie is 'n proteïnvrye surfaktant plaaslik berei ( dieselfde samestelling as Exosurf). 3. Exosurf®. (Kommersiële preperaat reeds in gebruik). Hierdie is 'n proteïnvrye sintetiese surfaktant. 4. Trehalose, 'n non-reduserende disakklaried van glukose. Addisioneel is daar ook in vitro studies gedoen waann die oppervlakte spanmngs aktiwiteite van die verskillende surfaktant oplossings vergelyk is. Die statistiese analise is gedoen in samewerking met Prof. J. Maritz wat 'n unieke metode ontwikkel en gepubliseer het om herhalende veranderlikes op 'n statisties verantwoordbare manier te ontleed. In die eerste van die studies, is LPM-I, Exosurf®, fisiologiese soutoplossing en 'n plaaslik bereide "Exosurf" (LPM-2), met 'n chemiese samestelling identies aan dié van kommersiële Exosurf®, evalueer. In 'n tweede studie is die fisologiese effekte van LPM-I vergelyk met trehalose of fisiologiese soutoplossing om die volgende te ondersoek: 1) Die bydrae van trehalose tot 'n mengsel van oppe, heksadekanol en tyloxapol (LPM-2). 2) Die gevolg van LPM-l surfaktant toediening op die konyn se brongo-alveolêre vloeistof samestelling. 'n Derde, in vitro studie, het die oppervlaktespannings-effekte van trehalose en of kalsiumbyvoegings tot DPPC-oplossings gemeet deur middel van die ring metode van Du Nouy, In die eerste in vivo studie verbeter oksigenasie en persentasie longaftakking tot dieselfde mate na LPM-l en Exosurf® toediening en word die hipotese van die proefskrif bevestig. In die breë gesien, is die tydsprofiele van LPM-l en Exosurf® ten opsigte van oksigenasie en persentasie longaftakking statisties betekenisvol beter en van 'n sneller aard, as die tydsprofiele van dieselfde indekse na die toediening van fisiologiese soutoplossing of LPM-2. Die tydsprofiel van dinamiese longvervormbaarheid, na die toediening van LPM-I of Exosurf®, is dieselfde, maar betekenisvol beter as die vervormbaarheid na toediening van LPM-2 of fisiologiese soutoplossing. Alhoewel die oksigenasie indekse in die geval van LPM-l en Exosurf® betekenisvol verbeter oor die studietydperk, vind volkome herstel tot die basislynwaardes (voor spoeling) nie plaas nie. Bykomend, geen van die surfaktante het na toediening enige noemenswaardige verbetering in longvervormbaarheid tot gevolg gehad nie. Die rede vir die swakker vertoning van LPM-2 en Exosurf is onbekend en sal in opvolg studie ondersoek word. In die tweede in vivo studie is dit duidelik dat trehalose op sy eie, 'n oneffektiewe surfaktant is aangesien die preperaat na toediening geen verbetering teweegbring ten opsigte van oksigenasie indekse, persentasie longaftakking, of long-dinamiese vervormbaarheid nie. Die toevoeging van trehalose tot LPM-2, om LPM-l te lewer, neem wel die aktiwiteit van LPM-l tot dieselfde in vivo vlak as dié van kommersiële Exosurf®, maar slaag nie daarim om 'n hoër fisiologiese in vivo aktiwiteit as dié produk te bereik nie. Die diere wat met fisiologiese soutoplossing behandel is toon geen verbetering in enige fisiologiese parameter nie. Die in vitro resultate wat verkry is deur die Du Nouy tensiometer toon hoër gemiddelde ordinaat oppervlaktespannings waardes vir 'n formule wat slegs uit DPPC bestaan, asook vir 'n mengsel van DPPC + trehalose. Die helling van die grafieke van hierdie oplossings is ook kleiner as die van die ander formulas wat daarop dui dat DPPC op sigself, en DPPC + trehalose, weinig vermoë het om oppervlaktespanning te verminder. Daarteenoor verlaag die volgende oplossings die oppervlaktespanning ten opsigte van gedistilleerde water betekenisvol en wel in In konsentrasie afhanklike manier by beide 21°C en 3rc: LMP-I-, LPM-2-, DPPC + trehalose + tyloxapol + CaCf2-, en LPM-2 + CaCf2. Die prominentste ligmikroskopiese bevindinge van die longe van die diere sluit in: Algemene limfvat dilatasie, stuwing, en long neutrofiel infiltrasie. Betreffende hierdie histologiese bevindinge is daar geen verskille aangetoon tussen die groepe nie. Hialienmembrane was teenwoordig in al die groepe, maar betekenisvol meer in die groep wat fisiologiese soutoplossing ontvang as vervangingsterapie. In die tweede in vivo studie is daar 'n betekenisvolle styging in die neutrofiel- en daling in makrofaagtelling, van die brongoalveolêre vloeistof spoeling in al drie die groep aangetoon. Terselfdertyd vind geen noemenswaardige daling in die perifêre (sistematiese) neutrofieltelling plaas nie. Hierdie bevindinge dui daarop dat die brongoalveolêre selveranderinge toegeskryf kan word aan verwerwing van neutrofiele vanuit 'n longstoringspoel eerder as rekrutering vanuit die sistemiese sirkulatoriese poel. Surfaktant (LPM-l), behandeling het geen betekenisvolle vermindering in long inflammasie teweeggebring nie. Epiteelskade was 'n algemene ligmikroskopiese bevinding in al die groepe. Die samestelling van die brongoalveolêre vloeistof verander na installering van LPM-I. Die prominentste verandering word waargeneem in die vetsuur samestelling terwyl die DPPC waardes onveranderd bly. Die vetsuur, palmitiensuur (palmitic acid), (CI6:0), verhoog betekenisvol na toediening van LPM-l. Daarteenoor verminder die konsentrasie van C16:1, C18:0 en C18:2. In kontras met vorige studies, beskryf die huidige studie hoër konsentrasies van fosfatidieletanolamien, moontlik as gevolg van tegniese verskille in die metingsmetodes. 'n Betekenisvolle verlaging in die fosfatidielcholine:sfingomiëlien (PC/SM) verhouding word waargeneem tussen die eerste en die finale longspoeling van die trehalose-groep, terwyl dit onveranderd bly in die diere wat LPM-1 of fisiologiese soutoplossing ontvang.

Thesis (PhD)-- Stellenbosch University, 2013. / ENGLISH ABSTRACT: Although the effect of inhaled corticosteroids (ICS) on the hypothalamic- pituitary-adrenal axis (HPA) has been regarded as a “benign physiological response”, a survey published in 2002 suggested that adrenal crisis is more common in asthmatic children on ICS than previously thought. Relying on clinical features to detect chronic adrenal insufficiency secondary to corticosteroids may not be wise, as these are non-specific and can therefore easily be missed. Accurate biochemical assessment of the whole axis to detect subclinical HPA suppression (HPAS) is thus desirable. A review of the literature indicates that basal adrenal function tests, including plasma cortisol profiles, do not identify which children can appropriately respond to stress. There is no evidence to suggest that the degree of the physiological adjustment of the HPA to ICS and/or nasal steroids (by reducing basal cortisol production), predicts HPAS. Cortisol profiles should therefore only be used to demonstrate differences in systemic activity of various ICS and delivery devices. Only two tests, considered as gold standard adrenal function tests [the insulin tolerance test (ITT) and the metyrapone test] can assess the integrity of the whole axis. / AFRIKAANSE OPSOMMING: Die outeurs van ´n opname wat in 2002 gepubliseer is stel voor dat ´n bynierkrisis meer algemeen by asmatiese kinders, wat inhalasie kortikosteroïede ontvang, voorkom as wat voorheen gedink is. Dit is strydig met die gevestigde opvatting dat die effek van IKS op die hipotalamiese-hipofise-bynier-as (HHB) ’n “goedaardige fisiologiese reaksie” is. Die kliniese kenmerke van kroniese bynierontoereikendheid sekondêr tot die gebruik van kortikosteroïede (KS) is nie-spesifiek en gevolglik onbetroubaar. ´n Akkurate biochemiese toets van subkliniese HBB onderdrukking (HHBO) sou gevolglik waardevol wees. ´n Literatuur oorsig toon dat toetse van basale bynierfunksie, insluitend plasma kortisol (K) profiele, nie kinders uitken wat toepaslik op stres sal reageer nie. Daar is geen bewyse dat die graad van fisiologiese aanpassing van die HHB, soos aangedui deur laer K-vlakke, na die gebruik van IKS en/of nasale steroïede (NS), HHBO voorspel nie. Serum K profiele is dus slegs van waarde om die sistemiese aktiwiteit van verskillende IKS en toedieningsstelsels te ondersoek. Slegs twee toetse, naamlik die insulien toleransie toets (ITT) en die metyrapone -(MTP)-toets (wat beide as die goue standaard van bynier funksie beskou word), kan die integriteit van die hele as meet. / Stellenbosch University / Medical Research Council / SA Thoracic Society / Harry Crossley Foundation / Red Cross Children’s Hospital.

Background: Trauma is a major cause of death and disability. Adverse events, such as prolonged prehospital time, hypoxia, hypotension and/or hyperventilation have been reported to correlate to poor outcome. Adequate cortisol levels are essential for survival after major trauma. In hypotensive critically ill patients, lack of sufficient amount of cortisol can be suspected, and a concept of critical illness related corticosteroid insufficiency has been proposed. Corticosteroid therapy has many adverse effects in critically ill patients and should only be given if life-saving. Correct measurement of serum cortisol levels is important but difficult in critically ill patients with capillary leakage. Estimation of the free and biologically active cortisol is preferable. In serum less than 10% of cortisol is free and biologically active and not possible to measure with routine laboratory methods. Salivary cortisol can be used as a surrogate for free cortisol, but salivary production is reduced in critically ill patients. Liver resection could reduce cortisol levels due to substrate deficiency. Aims: 1. Evaluate the occurrence of early adverse events in patients with traumatic brain injury and relate them to outcome. 2. Assess cortisol levels over time after trauma and correlate to severity of trauma, sedative/analgesic drugs and cardiovascular function. 3. Evaluate if saliva stimulation could be performed without interfering with salivary cortisol levels. 4. Assess cortisol levels over time after liver resection in comparison to other major surgery. Results: There was no significant correlation between prehospital time ³60 minutes, hypoxia (saturation <95%), hypotension (systolic blood pressure <90 mmHg), or hyperventilation (ETCO2 <4.5 kPa) and a poor outcome (Glasgow Outcome Scale 1-3) in patients with traumatic brain injury. Cortisol levels decreased significantly over time after trauma, but there was no correlation between low (<200 nmol/L) serum cortisol levels and severity of trauma. Infusion of sedative/analgesic drugs was the strongest predictor for a low (<200 nmol/L) serum cortisol. The odds ratio for low serum cortisol levels (<200 nmol/L) was 8.0 for patients receiving continuous infusion of sedative/analgesic drugs. There was no significant difference between unstimulated and stimulated salivary cortisol levels (p=0.06) in healthy volunteers. Liver resection was not associated with significantly lower cortisol levels compared to other major surgery. Conclusion: There was no significant correlation between early adverse events and outcome in patients with traumatic brain injury. Cortisol levels decreased significantly over time in trauma patients. Low cortisol levels (<200 nmol/L) were significantly correlated to continuous infusion of sedative/analgesic drugs. Saliva stimulation could be performed without interfering with salivary cortisol levels. Liver resection was not associated with low cortisol levels compared to other major surgery.

<p>Primarni glomerulonefritisi predstavljaju inflamatorna oboljenja bubrega, kod kojih su primarno zahvaćeni glomerulusi, ali promene na tubulointersticijumu imaju veliki značaj za tok i prognozu bolesti. Pored kliničko-laboratorijskih ispitivanja, perkutana biopsija bubrega zauzima značajno mesto u dijagnostici posebnih oblika glomerulonefritisa. Lipokalin vezan za neutrofilnu gelatinazu (NGAL) zauzima značajno mesto medju novijim biomarkerima u nefrologiji. Osnovna funkcija mu je transport gvoždja, ali ima ulogu i u regulaciji metabolizma gvoždja, regulaciji inflamacije, dok u masnom tkivu utiče na razvoj insulinske rezistencije i dijabetesa. Cilj ispitivanja je utvrditi nivo lipokalina 2 u serumu i urinu bolesnika sa primarnim glomerulonefritisom, te utvrditi postojanje korelacije izmedju nivoa lipokalina 2 i patohistolo&scaron;kog oblika glomerulonefritisa, stepenom bubrežne insuficijencije i brzinom progresije bubrežne insuficijencije. Takodje, cilj ispitivanja je bio analizirati povezanost lipokalina 2 sa odogovorom na primenjenu terapiju glomerulonefritisa. Ispitivanje je sprovedeno na 60 bolesnika sa dijagnozom primarnih glomerulonefritisa. Nivo lipokalina 2 je odredjivan pri postavljanju dijagnoze i nakon minimalno &scaron;est meseci lečenja. Rezultati studije ukazuju da bolesnici sa primarnim glomerulonefritisom imaju značajno veće nivoe lipokalina 2 u odnosu na zdrave osobe. Bolesnici sa proliferativnim oblicima primarnih glomerulonefritisa imaju veće nivoe NGAL-a u serumu i odnosa uNGAL/kreatinin, ali razlika nije statistički značajna. Nije utvrdjeno postojanje značajne razlike u prosečnim nivoima NGAL-a u serumu, niti urinu, pri postavljanju dijagnoze, izmedju bolesnika sa pozitivnim i negativnim efektom lečenja primarnog glomerulonefritisa. Utvrdjeno je postojanje korelacije izmedju nivoa NGAL-a u serumu i vrednosti kreatinina, ureje, mokraćne kiseline, klirensa kreatinina i broja leukocita, dok je sa nivoom NGAL-a u urinu utvrdjena korelacija sa klirensom kreatinina, dnevnom proteinurijom i serumskim albuminima. Utvrdjeno je postojanje statistički značajne razlike u prosečnim nivoima NGAL-a u serumu u zavisnosti od stadijuma bubrežne insufijencije. Nije utvrdjeno postojanje značajne razlike u prosečnim nivoima NGAL-a u serumu pri postavljanju dijagnoze, izmedju bolesnika sa povoljnim i nepovoljnim efektom lečenja na bubrežnu funkciju.</p> / <p>The primary glomerulonephritis are inflammatory kidney diseases. Glomerulus are primarily affected, but tubulointerstitial changes are very important for course and prognosis of the disease. In addition to clinical and laboratory testing, percutaneous renal biopsy has an important place in the diagnosis of specific forms of glomerulonephritis. Neutrophil gelatinaseassociated lipocalin (NGAL) occupies an important place among the newer biomarkers in nephrology. The main function of NGAL is transport of iron, whether it has a role in the regulation of iron metabolism, regulation of inflammation, while in adipose tissue affects the development of insulin resistance and diabetes. The aim of this study was to determine the level of lipocalin 2 in serum and urine of patients with primary glomerulonephritis and determine the existence of a correlation between the level of lipocalin 2 and histological forms of glomerulonephritis, the degree of renal insufficiency and speed of progression of renal insufficiency. Also, the aim of this study was to analyze the association of lipocalin 2 with the effect of therapy for glomerulonephritis. The study was conducted on 60 patients diagnosed with primary glomerulonephritis. The levels of lipocalin 2 were determined at diagnosis and after a minimum of six months of treatment. The study results show that patients with primary glomerulonephritis have significantly higher levels of lipocalin 2 compared to healthy people. Patients with proliferative forms of primary glomerulonephritis have higher levels of NGAL in serum and ratio uNGAL/creatinine, but the difference was not statistically significant. There was no significant differences in average levels of NGAL in serum or urine at the beginning, between patients with positive and negative effects of the treatment of primary glomerulonephritis. Correlation was found between the level of NGAL in serum and creatinine, urea, uric acid, creatinine clearance and the number of leukocytes, while the level of NGAL in urine correlated with creatinine clearance, the daily proteinuria and serum albumin. Statistically significant differences in mean levels of NGAL in serum depending on the severity of renal insufficiency were found. No evidence of significant differences in average levels of NGAL in serum at the beginning, among patients with favorable and unfavorable effects of treatment on renal function were found.</p>

Cardiovascular disease is the leading cause of death in the United States. Chronic short sleep duration is also a significant public health problem and has been linked to several markers and outcomes of cardiovascular disease. To date, inconsistency of assessments of sleep duration and insufficiency, use of covariates, and cardiovascular disease measurement across studies limits strong conclusions about the relationship between sleep duration, sleep insufficiency, and cardiovascular disease. The current study examined the association between sleep duration, sleep insufficiency, and a marker of preclinical coronary heart disease (i.e., carotid intima-media thickness) in a community sample using a cross-sectional design. Some evidence for a relationship between sleep duration and cIMT was found, with longer sleep duration predicting higher cIMT in some segments. Additionally, the interaction between sleep duration and sleep insufficiency was significant. However, neither of these effects were significant after adjusting for age and in some cases race/ethnicity, suggesting demographics may explain this association. Actigraphy and sleep diary duration assessments demonstrated significantly different correlations with cIMT in some segments, suggesting the nature of the assessment method may impact the strength or direction of the relationship between sleep duration and cIMT. Limitations and future directions are discussed.

Kidney failure is frequently associated with the risk factors linked to metabolic syndrome. Lipopolysaccharide (LPS) is a potent inflammatory molecule, which has increased absorption from the gut into blood circulation following a high fat and high-energy diet. We hypothesized that LPS from a high fat diet can amplify inflammation, thereby exacerbating chronic kidney disease and associated disorders. We have found that adding a high fat diet to renal insufficient mice significantly progressed their kidney disease as well as associated disorders, compared to both a high fat diet and renal insufficiency alone. Additionally, we were able to demonstrate in vitro that the combination of LPS and palmitic acid, a marker of high fat diet, induced inflammatory pathways significantly more than either LPS or palmitic acid alone. These results provide insight into connection between a high fat diet and the progression of chronic kidney disease as well as associated disorders.

This critical synopsis of prior work by Clive Beggs is submitted in support of a PhD by published work. The work focuses on venous and cerebrospinal fluid (CSF) anomalies associated with multiple sclerosis (MS) and other neurological diseases. MS is characterized by focal inflammatory lesions, which are often venocentric. Recently a vascular syndrome, chronic cerebrospinal venous insufficiency (CCSVI) has been linked with MS. This syndrome, which is characterized by constricted cerebral venous outflow, has become mired in controversy, with various studies producing conflicting findings, with the result that the science associated with CCSVI has become obscured. Clive Beggs work seeks to bring clarity to the debate surrounding CCSVI by characterizing physiological changes associated with constricted cerebral venous outflow. The work submitted here involves collaborative studies with Robert Zivadinov (University of Buffalo), Paolo Zamboni (University of Ferrara), and Chih- Ping Chung (National Yang Ming University of Medicine). The key findings of these studies are: (i) MS patients, diagnosed with CCSVI, exhibit greatly increased hydraulic resistance of the cerebral venous drainage system; (ii) MS patients experience loss of the small cerebral veins; (iii) MS patients exhibit reduced CSF bulk flow, consistent with mild venous hypertension; (iv) MS patients exhibit increased CSF pulsatility in the Aqueduct of Sylvius, which appears to be linked with mild venous hypertension associated with CCSVI; and (v) jugular venous reflux is associated with white matter and parenchymal volumetric changes in Alzheimer’s patients. Collectively, these findings suggest that extracranial venous anomalies are associated with changes in the intracranial physiology.

A leptospirose é uma zoonose de alta morbidade em humanos e um importante problema de saúde pública. Causada por bactérias do gênero Leptospira, a doença apresenta diversas formas clínicas e é especialmente importante em países em desenvolvimento. Síndrome pulmonar hemorrágica é a maior causa de óbito em pacientes com formas severas da doença. Os mecanismos patogênicos relacionados à síndrome pulmonar hemorrágica na leptospirose humana são desconhecidos. Com o objetivo de avaliar estes mecanismos patogênicos, 30 necrópsias (tecido pulmonar) de pacientes com síndrome pulmonar hemorrágica na leptospirose e 7 controles foram avaliados. Para determinar a participação os mecanismos patogênicos envolvidos, experimentos de histologia e imunohistoquímica (IgM, IgG, IgA, and C3) foram realizados em amostras de tecidos pulmonares, bem como dosagem sérica de auto-anticorpos específicos (anticardiolipina e anti-membrana basal) de amostras pareadas de soros de pacientes com leptospirose com e sem síndrome hemorrágica pulmonar e de indivíduos doadores de banco de sangue. Nos achados patológicos, os pacientes com síndrome hemorrágica pulmonar na leptospirose diferem dos controles com hemorragia pulmonar em alguns aspectos: moderada ou intensa presença de macrófagos na luz alveolar (97% versus 29%, respectivamente; p < 0.01); presença de membrana hialina na superficie alveolar (100% versus 0% respectivamente; p < 0.01); intensa necrose e regeneração de pneumócitos II (100% versus 0%, respectivamente; p < 0.01); e presença de plasmócitos no septo aveolar (80% versus 29%; p < 0.02). Nenhuma diferença estatisticamente significativa foi observada em relação ao número de outras células no septo alveolar. Leptospiras intactas foram raramente observadas. A detecção de antígeno de leptospira não foi correlacionada com a intensidade de hemorragia pulmonar. Em nenhum dos tecidos pulmonares estudados foi evidenciado alterações microscópicas sugestivas de coagulação intravascular disseminada. Deposição de imunoglobulina foi detectada na superfície alveolar de 18 de 30 pacientes com síndrome pulmonar hemorrágica na leptospirose. Três padrões de marcação de imunoglobulina e complemento foram observados em tecido pulmonar de pacientes com hemorragia pulmonar e leptospirose: (A) marcação linear delicada, como uma membrana, recobrindo a superfície luminal alveolar de pneumócitos I e II; (MF) marcação multifocal, aleatória ao longo do septo; e (I) marcação fraca granular, focal, intra-alveolar. Não houve diferenças significativas na concentração de auto-anticorpos contra membrana basal nos diferentes grupos estudados. Observamos diferenças significativas nos títulos de anticorpos IgM anticardiolipina entre a primeira e segunda amostra, nos pacientes com e sem hemorragia pulmonar (p<0.01 e p=0.04, respectivamente). Aumento significativo nos títulos de anticorpos anti-cardiolipina da classe IgG, bem como na relação IgG/IgM, foi observado apenas nos pacientes com hemorragia pulmonar (p=0.01 e p=0.01). Nós concluímos que o comprometimento pulmonar na leptospirose humana grave ocorre principalmente sob a forma de uma pneumopatia hemorrágica com características peculiares, cujo quadro morfológico difere de outras hemorragias pulmonares. Caracteriza-se pela deposição linear de imunoglobulina (IgM, IgG e IgA) e complemento(C3) na superfície luminal alveolar de pneumócitos I e II e multifocal nos septos alveolares. Associa-se à intensa necrose de pneumócitos I e II, regeneração de pneumócitos II, além de inflamação septal e alveolar / Leptospirosis is a zoonotic disease that is a cause of high morbidity and mortality in humans and is an important public health problem. Caused by bacteria of Leptospira genus, this disease presents diverse clinical manifestations and is especially important in developing countries. Leptospirosis pulmonary hemorrhage syndrome is the major cause of death in patients with the severe form of leptospirosis. The pathogenic mechanisms of this syndrome are unknown. With the purpose of identifying these pathogenic mechanisms, 30 necropsies (pulmonary samples) from patients with leptospirosis pulmonary hemorrhage syndrome and seven controls were evaluated. . To determine whether the immune system is involved, histology and immunohistochemistry (IgM, IgG, IgA, and C3) experiments were performed on lung tissue samples, as well sera measurements of autoantibodies (against the basal membrane and anti-cardiolipin) were performed in leptospirosis patients with and without pulmonary hemorrhage syndrome (in paired samples) and in healthy donors from a blood bank. We found that patients with leptospirosis pulmonary hemorrhage syndrome differed from control pulmonary hemorrhage patients in several features: the presence of moderate to high levels of macrophages in the alveolar space (77% versus 29%, respectively; p = 0.02), the presence of the focal hyaline membrane on alveolar surface (100% versus 0%; p < 0.01), extensive necrosis and regeneration of pneumocyte II cells (100% versus 0%; p < 0.01) and the presence of plasma cells in the alveolar septum (77% versus 29%, respectively; p =0.02). No statistically significant differences were observed in the number of others cells in the alveolar septae. Intact leptospires were rarely detected. Leptospiral antigen was not correlated with the intensity of the lesions. None of the patients showed microscopic evidence for disseminated intravascular coagulation. Immunoglobulin deposits were detected on the alveolar surface of 18/30 leptospirosis patients with pulmonary hemorrhage. Three staining patterns were observed for the immunoglobulins and C3 in the lung tissues of leptospirosis patients with pulmonary hemorrhage syndrom: (A) delicate linear staining adjacent to the alveolar surface, like a membrane covering the luminal surface of type I and II pneumocyte cells; (MF) random, multifocal staining along the alveolar septum; and (I) weak, focal intra-alveolar granular staining.. We were not able to show any significant difference in autoantibodies concentration in the different groups. We found significant difference between the titles of anticardiolipin IgM antibodies in the first and second sera sample from leptospirosis patients with and without pulmonary hemorrhage (p<0.01 e p=0.04, respectively). The increased in the titles of anti-cardiolipin IgG antibodies, as well IgG/IgM ratio was observed only in patients with pulmonary hemorrhage(p=0.01 and p=0.01). We concluded that the pulmonary involvement on severe human leptospirosis have particular characteristics, which the morphologic aspect differ from the others causes of lung hemorrhage. It was distinguished by linear deposition of immunoglobulin and complement (C3C) on the luminal alveolar surface of pneumocyte I and II cells. This event was associated with pneumocyte I and II cells necrosis, pneumocyte II regeneration and septal and alveolar inflammation