Concentric eyewall formation and eyewall replacement cycles are intrinsic processes that determine the intensity of a tropical cyclone, as opposed to purely environmental factors such as wind shear or the ocean heat content. Although extensive research has been done in this area, there is not a single widely accepted theory on the formation of secondary eyewall structures. Many previous studies focused on dynamic processes in the inner core of a tropical cyclone that would precede and ultimately lead to the formation of a secondary eyewall. Hurricanes Katrina and Rita in 2005 were frequently sampled by research aircraft which gathered a copious amount of data. During this time, Rita developed a secondary eyewall which eventually replaced the original eyewall. This thesis will investigate the formation of a secondary eyewall with particular emphasis on the rainband region, as observations show that an outer principal rainband transformed into the secondary ring. A high resolution, full physics model (MM5) initialized with global model forecast fields correctly predicted the secondary eyewall formation in Rita. The model output will be used to investigate both Katrina and Rita in terms of their PV generation characteristics since PV and vorticity maxima correlate well with wind maxima that accompany the eyewall and rainbands. Furthermore, dynamical processes such as vortex Rossby wave (VRW) activity in the inner core region will be analyzed. Comparison of the differences in the two storms might shed some light on dynamics that can lead to structure changes. Comparison of the model data with aircraft observation is used to validate the results. Doppler radar derived wind fields will be used to calculate the vertical vorticity. The vorticity field is closely related to PV and thus a manifestation of the PV generation process in the rainband. The investigation has shown that Rita?s principal rainband features higher PV generation rates at radii beyond 80 km. Both the azimuthal component and the projection of asymmetric PV generated by convection onto the azimuthal mean connected with the principal band are hypothesized to be of importance for the formation of the secondary eyewall. VRW were found not to be important for the initial formation of the ring but might enhance convective activity once the outer eyewall contracts.

No description available.

Organ-specific autoimmunity constitutes a large health problem, where both the clinical management and our understanding of the pathogenetic mechanisms need to improve. Women with Addison's disease have abnormally low levels of dehydroepiandrosterone (DHEA), its sulphate ester (DHEA-S) and androgens relative to age, and many patients complain of physical and mental fatigue and low stress tolerance. To define a suitable dose, the effect of oral DHEA replacement was evaluated in women with Addison's disease. DHEA was administered for three months to nine women with Addison's disease in either of two doses, 50 mg (n=5) or 200 mg (n=4). A dose of 50 mg restored the DHEA(S) and androgen levels to normal without altering the insulin sensitivity, body composition or serum lipid profile. Autoimmune polyendocrine syndrome type I (APS I) is a rare but useful model disorder of autoimmunity, characterised by multiple organ-specific autoimmune manifestations and high-titre autoantibodies and with adrenocortical insufficiency, Addison's disease, as one of its cardinal manifestations. Approximately 10-20% of APS I patients suffer from autoimmune hepatitis, which carries a high mortality, if untreated. The presence of putative antigenic targets in the liver was investigated. Cytochrome P4501A2 (CYP1A2) and aromatic L-amino acid decarboxylase (AADC) were identified as hepatic autoantigens with the use of APS I sera for immunofluorescent staining of normal human liver, Western blot of microsomal and cytosol fractions of human liver homogenate, and immunoprecipitation of in vitro transcribed and translated radioactively labelled proteins. The presence of CYP1A2- and AADC-antibodies was significantly correlated to AIH, and CYP1A2 antibodies inhibited enzyme activity in vitro. In conclusion, a daily replacement dose of 50 mg of DHEA sufficiently restores levels of DHEA, DHEA(S) and androgens in women with Addison's disease, without severe side-effects. We have further identified CYP1A2 and AADC as hepatic autoantigens associated with autoimmune hepatitis in APS I.

In this thesis, the importance of the growth hormone (GH)/insulin-like growth factor (IGF) system and sex steroids for male bone metabolism has been investigated, and the effects of continuous low dose GH replacement in GH deficient (GHD) adults. In a population-based sample of men, positive correlations were found between bone mineral density (BMD) and IGF-I, IGF-II, IGF binding protein (IGFBP)-3 and the testosterone/sex hormone binding globulin (SHBG) ratio. Serum IGFBP-3 and testosterone levels and weight accounted for 34% to 48% of the variation in BMD at different sites. Compared to healthy age matched controls, men with idiopathic osteoporosis had lower estradiol/SHBG ratio and higher SHBG levels. There were no differences between the groups in serum levels of IGF-I, IGFBP-3, 24 hour cumulated GH secretion or peak GH secretion. In the patients, there was a positive correlation between the estradiol/SHBG ratio and BMD in femoral neck. Treatment of patients and controls with GH 0.8 mg/day for one week resulted in similar increases in serum markers for bone turnover in both groups. Several positive correlations between indices of GH secretion and markers for bone turnover were found in the patients. Men with idiopathic osteoporosis were treated with GH, continuously (0.4 mg/day) or intermittently (0.8 mg/day for two weeks every third month), for two years followed by one year of follow-up. After two years, the BMD and bone mineral content in lumbar spine and total body and serum osteocalcin levels were increased in both groups. This increase was sustained one year post treatment. Treatment of GHD adults with a low fixed dose of GH (0.17 mg/day) for three months, resulted in increases in serum IGF-I and IGFBP-3 levels and lean body mass, and a reduction in fat mass and total and low-density lipoprotein cholesterol levels. These beneficial effects were accomplished without serious side effects. These findings indicate that: i) the sex hormone and GH/IGF systems are important in male bone metabolism, ii) a combination of subtle disturbances in these two systems could contribute to the development of male idiopathic osteoporosis, iii) GH treatment could be considered as a treatment option in this condition.

Delirium is common among old patients admitted to hospital, but is often a neglected problem in patient care. The principal aim of this thesis was to evaluate aspects of delirium in relation to incidence, risk factors, behavioural changes, cognitive function and health-related quality of life (HRQOL). A further aim was to describe patients’ experiences of being delirious. The study was prospective, descriptive and comparative, with repeated measures (six-month follow up). The sample consisted of 225 consecutive patients, aged 65 years or older, who were to be operated on due to hip fracture or hip replacement. Exclusion criteria were serious cognitive disorder or delirium on admission. Data were collected via frequent daily observations, cognitive functioning tests (MMSE), HRQOL questionnaires (SF-36) and interviews. Delirium was assessed according to the DSM-IV criteria. A total of 45/225 became delirious, with an incidence of 24.3% among patients undergoing hip fracture surgery and 11.7% among those with hip replacement surgery. A predictive model for delirium included four factors: impaired hearing, passivity, low cognitive functioning, and waiting more than 18h for hip fracture surgery. Disorientation and urgent calls for attention were the most frequent behavioural changes in the prodromal phase prior to delirium. Delirium in connection with hip fracture revealed deteriorated HRQOL and cognitive functioning when measured at a six-month follow-up. The experience of being delirious was described by the patients as a sudden change of reality. Such an experience gave rise to strong emotional feelings, as did recovery from delirium. Nurses’ observations of behavioural changes in old patients with impaired cognitive function may be the first step in managing and reducing delirium. The predictive model of delirium ought to be tested further before use in clinical practice.

The goals of this thesis are to evaluate quality of life (QoL) in adult patients with growth hormone deficiency (GHD) in relation to population normative data, to construct a preference-weighted index (utility) from a disease-specific QoL measure and to assess it in a clinical context. The study included samples from the general population and patients with GHD from four European populations: England & Wales, the Netherlands, Spain and Sweden. The country-specific patient cohorts were retrieved from KIMS (Pfizer International Metabolic Database). A questionnaire was developed that contained items from existing QoL questionnaires including, among others, Quality of Life Assessment in Growth Hormone Deficiency in Adults (QoL-AGHDA) and the EQ-5D. The QoL-AGHDA is a disease-specific measure for use in adults with GHD. The EQ-5D is a generic instrument which describes health states for which country-specific preference-based weights are available. Thus, it was possible to generate preference-weighted indices (utilities) based on data generated by both instruments. This thesis reports QoL-AGHDA normative values for the populations of England & Wales, the Netherlands, Spain and Sweden, and confirms the extent of QoL impairment in patients with GHD in comparison with the general population. Long-term GH replacement resulted in sustained improvements in overall QoL towards normative country-specific values, as well in most of the dimensions that were impaired before treatment. For use in health economic evaluations, models for generating utilities (QoL-AGHDAutility) from QoL-AGHDA were developed. It is believed that these models may facilitate medical decision making, given that they provide a tool for obtaining utilities in the absence of directly collected preference-weighted indices. QoL-AGHDAutility effectively monitored treatment effects in patients with GHD. Moreover, this study confirmed a QoL-AGHDAutility deficit before treatment and a gain after starting GH replacement. The novel aspect of the present approach was to apply preference-weighted indices derived from a disease-specific measure to assess QoL in the clinical context, together with patient demographic and clinical characteristics. The robustness of this analysis is reinforced by the fact that utilities in both general and patient populations were generated using the same methodology.

A pair of studies investigating the deposition and surface chemical properties of ultrathin metal films were pursued: (i) Pt-Co alloys on Mo(110); and (ii) Pd on Pt(111). Experimental measurement was based on a combination of electron spectroscopy (low energy ion scattering spectroscopy, X-ray photoelectron spectroscopy, Auger electron spectroscopy, and low energy electron diffraction) and electrochemistry (voltage efficiency, voltammetry, and coulometry). Mixed-metal preparation of Pt-Co films by thermal vapor deposition (TVD) resulted in a thin-film binary alloy. Careful analysis revealed a substantial divergence between the composition at the interface and that in the interior. This outcome was observed for all compositions and allowed for the construction of a ?surface phase diagram?. The proclivities of the alloys of pre-selected compositions towards enhanced catalysis of the oxygen-reduction reaction were assessed in terms of their voltage efficiencies, as manifested by the open-circuit potential (OCP) in O2-saturated dilute sulfuric acid electrolyte. The particular alloy surface, Pt3Co (XPt=3,XCo=1), whether from the thin film or a bulk single crystal, exhibited the highest OCP, a significant improvement over pure Pt but still appreciably lower than the thermodynamic limit. Under test conditions, the degradation of thusly-prepared films was primarily due to Co corrosion. Ultrathin Pd films on well-defined Pt(111) surfaces, with coverages from 0.5 to 8 monolayers (ML), were prepared by surface-limited redox replacement reaction (galvanic exchange) of underpotentially deposited Cu. Spectroscopic data revealed that films prepared in this manner are elementally pure, pseudomorphic to the substrate, and stable, independent of the surface coverage (?) of palladium. Analysis of the voltammetric profiles in the hydrogen evolution region revealed unique properties of hydrogen adsorption unseen in bulk electrodes. Notably, at 1 ML coverage, a step-free film was produced that did not exhibit hydrogen absorption. At higher coverages, digital (layer-by-layer) deposition gave way to 3D islands in a Stranski- Krastanov growth mode; under these conditions, onset of bulk-like behavior was observed. This method makes possible the synthesis of well-ordered noble-metal films in the absence of high-temperature treatment

Adverse effects of cyclooxygenase (COX) inhibitors on bone healing have previously been demonstrated in diaphyseal fracture models in animals. In spite of that, they are widely used as postoperative analgesics in orthopaedic surgery. After joint replacement, a bone repair process starts at the interface between bone and cement. If this process is disturbed, the prosthesis may never become rigidly fixed to the bone, leading to migration and with time loosening. This thesis investigates the effects of a selective COX-2 inhibitor (parecoxib or celecoxib) on bone healing in metaphyseal bone in a rat model and on knee prosthesis migration after total knee replacement, as measured with radiostereometric analysis. Blood loss, postoperative recovery, and the 2-year subjective outcome, were also measured. In addition, a hemoglobin dilution method for blood loss estimation, used in this thesis, was evaluated. In the first study, pull-out force of a screw inserted in metaphyseal bone of the tibia in rats was only marginally decreased by parecoxib after 7 days but not after 14 days. In the second and third study, celecoxib treatment resulted in less pain postoperatively in conjunction with total knee replacement (TKR), but no effects were seen on blood loss, range of motion, subjective outcome, or prosthesis migration after 2 years. Comparing the true blood loss of blood donors with the blood loss estimated by the hemoglobin dilution method, this method was found to underestimate the true blood loss. It is therefore not suitable for calculation of the absolute blood loss volume, but may be used for a rough estimate. In summary, celecoxib and presumably other cyclooxygenase inhibitors seems not likely to increase the risk of prosthesis loosening.

Background: Estrogen has been reported to enhance well-being and quality of life during the climacteric phase. In women with an intact uterus estrogen treatment is always combined with progestins in order to protect the endometrium from hyperplasia and malignancies. However, in certain women the addition of progestins causes cyclicity in negative mood symptoms and physical symptoms similar to those encountered during ovulatory cycles in women with premenstrual dysphoric disorder (PMDD). The ovarian hormones estradiol and progesterone have profound effects on a number of neurotransmitter systems in the brain, such as the gamma aminobutyric acid (GABA) system and the serotonergic system. Progesterone metabolites, such as allopregnanolone and pregnanolone (also referred to as neurosteroids) modify the GABAA receptor in the central nervous system (CNS) and enhance GABAergic inhibitory transmission. Neurosteroid sensitivity in human studies can be studied by saccadic eye movement measurements using pharmacodynamic challenges with pregnanolone. Altered neurosteroid sensitivity has been suggested as a possible contributory factor to the progesterone/progestin-induced adverse mood effects of hormone replacement therapy (HRT). There is also evidence of estrogen treatment affecting the serotonergic system in postmenopausal women, although progestin addition has been less well studied. Aims and method: The aim was to investigate whether the negative mood symptoms experienced during the progestin or progesterone phase of HRT were associated with changes in neurosteroid sensitivity, or changes in platelet serotonin uptake site (transporter) and serotonin2A (5-HT2A) receptor binding. The intention was also to investigate whether hormonal changes during the normal menstrual cycle affect these peripheral serotonergic parameters. Postmenopausal women with climacteric symptoms were given HRT in two randomized, double-blinded, placebo-controlled crossover studies. The women received 2 mg estradiol (E2) continuously during 28- day cycles. Synthetic progestins or natural progesterone were added sequentially during the last 14 days, and compared to a placebo addition. Before treatment, as well as during the last week of each treatment cycle the pharmacodynamic response to pregnanolone was assessed using saccadic eye movement measurements. Throughout the studies daily symptom ratings were made. In the study regarding synthetic progestins, platelet serotonin transporter and 5-HT2A receptor binding were assayed before entering the study, as well as during the last week of each treatment cycle. In the study on reproductive women, blood samples were collected for analysis of platelet serotonin transporter and 5-HT2A receptor binding at six different points in time during the menstrual cycle. Results and conclusion: The addition of synthetic progestins to estrogen treatment increased negative mood symptoms and physical symptoms, whereas positive symptoms decreased. The addition of progestins also increased the sensitivity to pregnanolone. The addition of natural progesterone to estrogen treatment increased the sensitivity to pregnanolone. However, in this study the pregnanolone sensitivity was enhanced also during estrogen treatment. Women expressing cyclicity in negative mood symptoms were more sensitive to pregnanolone than women without symptom cyclicity. Thus, it is evident that mood deterioration during HRT is associated with altered neurosteroid sensitivity. Platelet serotonin transporter and 5-HT2A receptor binding did not change during the different treatment conditions in HRT. Thus, we were unable to explain the negative mood changes of HRT by use of these peripheral serotonergic parameters. In the study on reproductive women however, it was clear that the serotonergic variables did change during the menstrual cycle. Binding to the serotonin transporter was higher in the late follicular phase than in the ovulatory, early luteal or mid-luteal phases. Binding to the 5-HT2A receptor was higher in the early follicular phase and the early luteal phase than in the mid-luteal phase. These findings may provide a link between the ovarian steroids, and the GABAergic and serotonergic neurotransmitter systems, which in turn, could explain part of the specific vulnerability that women have for the development of adverse mood effects during HRT, mood and anxiety disorders and for the deterioration of mood so frequently seen during the luteal phase.

Hintergrund: Die regionale Citrat-Antikoagulation im Rahmen der Nierenersatztherapie hat bei interdisziplinären Intensivpatienten in den letzten Jahren zunehmend an Bedeutung gewonnen. Für Schwerbrandverletzte existieren bislang kaum Untersuchungen zu diesem Verfahren. Ziel dieser Arbeit war es, die kontinuierliche Nierenersatztherapie mit Citrat-Antikoagulation bei Intensivpatienten mit akutem Nierenversagen nach schwerem Verbrennungstrauma im Hinblick auf Praktikabilität, Effektivität und Komplikationshäufigkeit sowie die Stabilität von Elektrolyt- und Säure-Basen-Haushalt und Gerinnung zu untersuchen. Daneben sollten Aussagen zur Prävalenz des akuten Nierenversagens in dieser Patientengruppe und zu dessen Einfluss auf die Letalität getroffen werden. Methode: Im Rahmen einer retrospektiven Untersuchung wurden unter Verwendung von Patientenakten und Patientendatenmanagementsystem (PDMS) Daten von 27 Schwerbrandverletzten (VKOF ≥ 20% oder ABSI ≥ 8) mit akutem Nierenversagen ausgewertet, die zwischen Januar 2004 und Dezember 2009 im Verbrennungszentrum des Klinikums Sankt Georg Leipzig mit einer kontinuierlichen Nierenersatztherapie behandelt wurden. Bei allen Patienten kam ein Dialysegerät Prisma CFM (Gambro Hospal GmbH, Deutschland) mit einer Polyacrylnitril-Filtermembran (AN 69, Filterset M 100) der gleichen Firma zum Einsatz. Standardverfahren war eine kontinuierliche veno-venöse Hämodiafiltration (CVVHDF) im Prädilutionsmodus. Bei 18 Patienten wurde eine regionale Citrat-Antikoagulation als Antikoagulationsverfahren eingesetzt, bei 7 Patienten eine systemische Heparin-Antikoagulation, bei 2 Patienten kamen alternierend beide Verfahren zum Einsatz. Für die 18 Patienten unter regionaler Citrat-Antikoagulation erfolgte eine detaillierte Analyse des akuten Nierenversagens unter Einbeziehung des klinischen Verlaufes, der Laborparameter und der Behandlungsdaten des Nierenersatzverfahrens. Ergebnisse: Die Prävalenz eines akuten Nierenversagens mit Notwendigkeit zur Nierenersatztherapie bei Schwerbrandverletzten betrug 15,5%. Die Sterblichkeitsrate war in der Patientengruppe mit Nierenversagen etwa fünffach erhöht (25,9 vs. 4,8%). Die Letalitätsrate bei den Patienten unter systemischer Heparin-Antikoagulation war bei vergleichbarem Verbrennungsausmaß etwa fünfmal höher als unter regionaler Citrat-Antikoagulation (57,1 vs. 11.1%). Die Nierenersatztherapie wurde im Median nach 6 Tagen begonnen, die mediane Behandlungsdauer pro Patient betrug 7 Tage. Bei Start der CVVHDF wiesen 94,4% der Patienten einen Schockzustand mit Notwendigkeit einer Vasopressortherapie auf, 83,3% zeigten schwere Dysfunktionen in mindestens 3 Organsystemen, der SOFA-score lag im Median bei 14. Bei einer mittleren Citratkonzentration von 3,6 mmol/l Blut im Extrakorporalkreiskauf konnte eine mediane effektive Filterlaufzeit von 67 Stunden erreicht werden. Hypocalcämien (<0,9 mmol/l) fanden sich in 1,1%, Hypercalcämien (>1,3 mmol/l) in 0,4%. Hypernatriämien (<150 mmol) waren mit 0,4% ebenso selten wie metabolische Alkalosen (pH >7,50 und BE >4) mit 0,2%. Im Gesamtdialysezeitraum von 3790 Stunden gab es nur ein Blutungsereignis, die Gerinnungsparameter zeigten bis auf einen passageren Abfall der Thrombozytenzahl keine signifikanten Veränderungen. Die erzielte mittlere Dialysedosis war mit 35,1 ml/kg Körpergewicht/h ausreichend hoch. Neben einer Reduktion der Nierenretentionsparameter Serum-Creatinin und Serum-Harnstoff fanden sich unter dem Nierenersatzverfahren verbesserte Oxygenierungsindices und sinkende SOFA-scores. Keiner der überlebenden Patienten war zum Zeitpunkt der Entlassung dialysepflichtig. Zusammenfassung: Die CVVHDF unter regionaler Citrat-Antikoagulation ist bei Schwerbrandverletzten ein effektives und in Bezug auf Säure-Basen-Haushalt, Elektrolyte und Gerinnung sicheres Verfahren. Neben einer effektiven Elimination harnpflichtiger Substanzen konnten eine exzellente Stabilität von Elektrolyten und metabolischen Parametern sowie eine suffiziente Antikoagulation im Extrakorporalkreislauf mit niedrigem Blutungsrisiko und konstant langen Filterlaufzeiten nachgewiesen werden. Die Prävalenz des akuten Nierenversagens bei Schwerbrandverletzten ist hoch, die Letalität bei Vorliegen des Organversagens vier-bis fünffach erhöht.