Ausgangslage: Die genetischen Grundlagen der chronischen Pankreatitis sind zum heutigen Zeitpunkt nur unzureichend erforscht. Mutationen im Gen des Serinprotease-Inhibitors Kazal Type 1 (SPINK1) und heterozygote Mutationen im CFTR-Gen wurden in zahlreichen Untersuchungen gehäuft bei Patienten mit chronischer Pankreatitis nachgewiesen. Methodik: Es wurden retrospektiv anhand der Daten der Pankcourse Studie (2004-2007) Untersuchungen bei Patienten mit chronischer Pankreatitis zur Häufigkeit von SPINK1- und CFTR-Mutationen sowie zum Manifestationszeitpunkt der Erkrankung durchgeführt. In Fall-Kontroll-Analysen wurde untersucht, ob sich Unterschiede in den jeweiligen Krankheitsverläufen nachweisen lassen. Ergebnisse: Eine heterozygote SPINK1-Mutation (N34S) konnte bei 11,5% und eine CFTR-Mutationen bei 24% der untersuchten Patienten nachgewiesen werden. Bei Patienten mit SPINK1-Mutation fand sich im Gegensatz zu Patienten mit CFTR-Mutation eine signifikant frühere Krankheitsmanifestation als bei Patienten ohne Mutationsnachweis. Patienten mit SPINK1-Mutation mussten zudem seltener und später operiert werden als Patienten ohne Mutation. Bei Patienten mit CFTR-Mutation zeigte sich ein signifikant früheres Auftreten von Stenosierungen und Konkrementen des D. pancreaticus im Vergleich zur Kontrollgruppe. Schlussfolgerung: Die ätiologische Bedeutung von SPINK1- und CFTR-Mutationen konnte bestätigt werden. Es fanden sich einzelne Hinweise auf einen durch die jeweilige Mutation verursachten charakteristischen Krankheitsverlauf, was durch weitergehende Untersuchungen bestätigt werden muss.

Die chronische Pankreatitis (CP) ist eine wiederkehrende, entzündliche Erkrankung des Pankreas. In den letzten Jahren wurden mehrere Kandidatengene, die zur Entstehung einer CP prädisponieren, identifiziert. Zu diesen Genen gehören PRSS1, PRSS2, SPINK1, CFTR und CTRC. Der Pathogenese der genetisch bedingten CP scheint dabei eine frühzeitige, intrapankreatische Aktivierung von Trypsin zugrunde zu liegen. Cathepsin B (CTSB), eine in Lysosomen vorkommenden Protease, ist in der Lage Trypsinogen zu aktivieren. Genetisch zeigte sich eine Assoziation der p.L26V Variante bei tropisch-kalzifizierender CP, welche bei idiopathischer CP nicht bestätigt wurde. Neben CTSB ist CTSL die am zweithäufigsten vorkommende lysosomale Protease. Funktionelle Untersuchungen zeigten, dass CTSL ein inaktives Trypsin freisetzt. Im Mausmodell zeigten sich bei Ctsl-/- Tieren bei experimentell induzierter Pankreatitis zwei Effekte. Zum einen war die Trypsinaktivität erhöht, zum anderen verlief die Pankreatitis milder, da vermehrt Apoptose anstelle von Nekrose der Azinuszellen auftrat. In dieser Studie wurde mittels uni-direktionaler DNA-Sequenzierung das gesamte CTSL1 untersucht. Dabei fanden wir insgesamt drei seltene nicht-synonyme Varianten. Die Variante c.5A>C (p.N2T, rs112682750) fanden wir bei einem Patienten, wobei diese Variante bereits bei Kontrollen beschrieben wurde. Die Varianten c.126+1G>A und c.915A>C (p.E305D) lagen bei jeweils einer Kontrolle vor. Sowohl seltene als auch häufige Varianten und die berechneten Haplotypen zeigten keinen signifikanten Verteilungsunterschied zwischen Patienten und Kontrollen. Demnach besteht keine Assoziation von Varianten des CTSL1 und CP.

Due to high frequency and occurrence of chronic kidney diseases in Taiwan, as well as the low public awareness, this research aims to explore the knowledge construction process of Hemodialysis in health broadcasting programs from a health communication point of view. This research intended to answer the following questions: 1) What are health radio program audience types? 2) How does the knowledge on hemodialysis differ among audiences? 3) What is the knowledge construction process among audience in regards to hemodialysis? Data were collected by ten episodes of the Kaohsiung Police Ration Station¡¦s ¡§Medical Network¡¨ program for a six month period (January ~ June 2011). This research has utilized content analysis method on the audience type, quantitative description on questions identified by the audience and qualitative methods to summarize and interpret the audience¡¦s knowledge construction process on hemodialysis. The results showed that the main audiences for health broadcast programs are mostly male, age 31 to 50 years, holding profession as drivers, service personnel and potential patients. Among them, the potential patients and their family members most often times ask diagnostic questions, falling into the compelled group in seek of knowledge. Those who have not been diagnosed with the disease often times bring up knowledge confirmation questions, belonging to the proactive knowledge chaser group. These two groups also demonstrated different hemodialysis knowledge construction processes. While the radio program host plays the role of knowledge enhancer to the diagnostic-need group (potential patients), the role transfers to a knowledge transformation model for the knowledge confirmation group (non-patients). Participating physicians follow the treatment process of ¡V examination, diagnosis and treatment to deliver information. The research process shall provide broadcasters or other media professionals a best practice on how the audience absorbs information - to study the distribution and motives of the audience and to deliver the knowledge of health and illnesses.

Despite intensive research on the neurobiological mechanisms of chronic pain, this therapeutic area remains one of the least satisfactorily covered by current drugs. Glutamate activates two major classes of receptors: ionotropic and metabotropic. Ionotropic receptors are classified into three major subclasses:a-amino-3- hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA), kainate and N-methyl-D-aspartate (NMDA). NMDA receptor activation, at the level of the spinal cord and peripheral tissue has been shown to play an important role in the facilitation of nociption in several animal models. Although the efficacy of NMDA receptor antagonists in various experimental and clinical pain situations has been well documented, their use as analgesics is limited by serious side effects such as memory impairment, psychotomimetic effects, ataxia and motor incoordination. Two promising current approaches to obtain effective analgesia devoid of side effects are by subtype-selective NMDA receptor antagonism in central nervous system (CNS) or peripheral use of NMDA receptor antagonist that do not interfere with central glutamate processing. NR2B subunit of NMDA receptor was predominantly found in the superficial dorsal horn of spinal cord. Recent discoveries have revealed that the transfection of small interfering RNAs (siRNAs) into animal cells results in the potent, long-lasting post-transcriptional silencing of specific genes. Thus, two approaches of antagonizing NMDA receptor in CNS and peripheral nervous system (PNS) for pain relief using siRNAs or pharmacological agents are investigated in this study. The first approach involves intrathecal administration of NR2B-siRNA into subarachnoid space and transfection of siRNA into cell of spinal cord by transfection agent of polyethylenimine (PEI). Formalin test was used to induce inflammatory pain in the hind paw of rats. Behavior response to formalin test was observed and recorded on 3rd, 7th, 14th, and 21th day after injection of siRNA. The spinal cords were dissected immediately after formalin test and used for analysis of mRNA and protein. The results revealed that the use of siRNA targeting the NR2B subunit could abolish formalin induced pain behaviors and not impair motor coordination in rat model. The expression of NR2B mRNA and its associated protein as demonstrated by real time reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were decreased. Significant reduction of NR2B immunoreactivity in dorsal horn of spinal cord were detected after 7 days treated by NR2B siRNA. The peak effect of gene knockdown occurred on day 3 for mRNA and day 7 for its protein, following intrathecal injection of 5 µg of siRNA targeting NR2B subunit. The inhibition of NR2B mRNA and protein lasted about 14 days and recovered on 21th days after injection of siRNA. The nociceptive response induced by formalin was decreased during the period of downregulation of NR2B protein. A novel intrathecal delivery of siRNA transfected with PEI into cell of dorsal horn reduced formalin-induced pain. The second approach involves subcutaneous injection of NMDA receptor antagonist and topical use of alpha2-adrenergic agonist for abolishing surgical pain. Additionally, we proved the upregulation of glutamate receptors in human inflamed skin. The study examined whether the peripheral ionotropic glutamate receptors (iGluRs) increased in inflamed human skin taken from patients having inflammatory pain over inflamed skin and surrounding area. Real time RT-PCR and western blot were used for quantitation of mRNA and protein of iGluR in normal and inflamed human skin. A significant increase in mRNA and protein for the subunits of NMDA, AMPA, and kainate receptor were detected in inflamed skin when compared to normal skin. The results demonstrate that mRNA and protein level of iGluRs are increasingly expressed during states of persistent inflammation, and that this increased activity may be involved in mediating clinical inflammatory pain in human skin. To examine the postoperative analgesic effect and adverse effect of local NMDA receptor antagonist (ketamine), ketamine (0.3%, 3 ml) or saline was subcutaneous infiltrated pre-incisionally in 26 patients equally assigned to two groups undergoing circumcision surgery. The saline-infiltrated subjects also received 9-mg intramuscular ketamine into the upper arm to control for any related systemic analgesic effects. The postoperative analgesic and adverse effects were followed for 24 hours. For ketamine infiltrated patients, the time interval until first analgesic demand was prolonged and the incidence of pain free (pain score = 0) during movement and erection was significant higher than saline infiltrated patients. No significant differences were noted in the incidence of adverse effects between the two groups. Pre-incisional subcutaneous infiltration of ketamine acting via a peripheral mechanism can suppression postoperative pain after circumcision surgery. Apraclonidine hydrochloride (AH) is a topical, relatively selective alpha2-adrenergic agonist that has limited access to the CNS and exhibits fewer systemic (adverse) effects such as dizziness and hypotension. Eighty patients scheduled for arthroscopic knee surgery received either intraarticular (IA) normal saline, 50 ug IA AH, 150 ug IA AH, or 150 ug IA clonidine subsequent to surgery. The IA application of 150 ug apraclonidine and 150 ug clonidine provide similar degree of postoperative analgesia and similar incidence of adverse effect. The promise is that both approaches attenuating nociception state devoid of CNS adverse effects provide novel approach for the management of chronic pain.

No description available.

Abstract Research Objectives¡GThe chronic diseases of the elderly not only influence their life quality but also become a great burden of the society on the health care costs. International studies focused on the utilization of medical care resources for diabetes mellitus patients of comorbidity, such as cardiovascular disease¡Bcerebrovascular disease¡Brenal disease and hypertensive. However, systemic analyses on the medical care utilization of the diabetes patients with comorbidity have not been well-studied in Taiwan. The purposes of the study are to quantitatively analyze the relationships between the number of comorbidity and the utilization of medical are resources, and to further discuss the interference on the utilization of medical care resources among individual diseases of the comorbidity. The research questions are: What is the effect of comorbidity on the type and volume of the utilization of medical care resources? Which comorbidity pattern has the highest effect? Methods¡GBased on the databases established by the Bureau of National Health Insurance during the period of 2005 to 2006, the diabetes patients with aged 65 or older have been analyzed. The data analyses have been carried out by Chi-square test, T-test, Pearson¡¦s correlation, and Multiple Regression and Logistic regression. Result¡GOur results showed that the clinic-visiting frequencies of outpatients with a comorbidity score of 0, 1, 2 and 3 are 52, 69 , 70 and 86 times, respectively, and their expenses are NT dollars 50,505, 97,347, 83,006 and 146,954, respectively. The hospital admission frequency of inpatients with a comorbidity score of 0, 1, 2 and 3 are 2 , 3, 3 and 5 times, respectively; the length of stay are 24, 29, 27 and 60 days, respectively; and the inpatient expense are NT dollars 118,079, 174,727, 147,639 and 271,725 respectively. In addition, the logistic regression model showed that ORs for the probability of hospitalization for the patients with comorbidity scores of 1, 2 and 3 were higher than those with the comorbidity score of 0¡]OR=1.689, OR=1.597, OR=3.319¡^respectively. Conclusion¡GA clear gradient was observed between the number of comorbidities and the increased health care utilizations. Moreover, comorbidity among diabetes patients is associated with considerable consequences of health care and related costs. In addition, current single-disease approach of diabetes care should be extended to the integrated care modules, which must be generic and include comorbidity disease in order to meet the complex health care demands of diabetes patients in the future.

Lic.avh. Luleå : Luleå tekniska univ., 2009. / Härtill 2 uppsatser.

The primary purpose of this study was to find out which variables lie behind the fact that patients who respond well to treatment of chronic pain differs from those who do not. We used logistic regression to predict group belonging based on the self-reported health surveys, i.e if different answers in the surveys can predict whether a patient is “responsive” or “unresponsive”. By bootstrapping 176 samples, and aggregating the results from 176 logistic regressions based on the sub-samples, we calculate an averaged model. The variables anxiety and physical health were significant in 76% and 70% of the models respectively, while depression was significant in 30% of the models. Gender was significant in 15% of the models and health status in 0,006%. The averaged model correctly classified the most unresponsive patients at cut-off value 0.5. As the cut –off value was increased, the number of correctly classified unresponsive patients decreased while the number of correctly classified responsive patients increased, as well as unresponsive patients classified as responsive. We concluded that the model did not discriminate enough between the two groups. We were also interested in finding out how the variables anxiety, depression, heath status, willingness to participate in activities as well as engagement in activities, mental and physical health relate with one another. The results from confirmatory factor analysis showed that a patient’s health status is highly related to their physical health and activity engagement while pain willingness and engagement in activity were least related. Furthermore, the analysis showed that mental health is highly related with anxiety and health status, indicating that mental health is indeed important to reflect upon when considering the health status of a patient.

L’irruption d’une maladie chronique constitue une rupture dans la vie des individus, qui les conduit à repenser leur projet professionnel. A partir d’un dispositif collectif d’échanges sur le thème du maintien ou du retour au travail, de 35 entretiens semi-directifs de recherche et de 27 entretiens d’orientation, notre étude tend à montrer que le projet des personnes malades s'élabore soit dans la continuité de leur situation de travail antérieure, soit dans un désir de changement. Les activités des sujets, de travail ou hors travail, apparaissent comme un moyen de se dégager de la maladie et d’éprouver ce dont on est capable. Elles sont sources de projection de soi dans l’avenir et permettent, alors même que la référence à celui qu’on était auparavant n’est plus valide, d’étayer le projet sur des expériences concrètes. En cela, elles sont un déclencheur des réorganisations. Le projet est donc un moyen de restauration des capacités d’action sur soi et sur son environnement. / Whenever a chronic disease arises, it does mark a break in people’s life, which often leads them to reconsider their vocational project. Through a collective workshop about how to hang on or to return to work and the addition of 35 semi-directive research interviews and 27 counseling interviews, we aim to show that people suffering from a chronic disease build their vocational project, by either carrying on their previous professional life or trying to change it. Both work and off- work activities seem to be a way of escaping the disease and assessing their own capabilities. Through activities, people can picture themselves in the future and build a project based on real experiences, although they are not anymore the person they used to be. Thus, these activities cause reorganizations. The project becomes therefore a way of restoring the ability to act by oneself and on the environment.

This qualitative study describes the experience of eight men with fibromyalgia (FM). Data from repeated semi-structured interviews was analysed using the constant comparative method, in order to generate a grounded theory. The specific aims were to explore how individuals perceived and made sense of their condition, and to discover the impact of FM upon their sense of identity and intimate relationships. Two core categories emerged from data analysis - loss and limited understanding. Losses pertained to the men's capabilities and activities; role and identity; work; and relationships. Limited understanding was described in relation to three levels of experience: limited understanding by the individual sufferer; by other people; and by health care professionals. Various intervening and contextual variables were identified for each phenomenon. Analysis suggested that loss is more likely to be pronounced where pain is severe and constant; the degree of incapacity is high; and there is a complete cessation of work. Intervening conditions likely to reduce the sense of loss included role expectations consistent with capabilities; absence of young dependants; a flexible work environment; living with a partner; favourable social comparisons; high self-efficacy and accepting attitude towards illness. Limited understanding was likely to be more pronounced where the individual perceived no rational link between the triggering event and symptoms of FM, and where new difficulties were encountered. The individual was more likely to perceive that others misunderstood their situation if they were not using a mobility aid themselves. Individuals were more likely to perceive limited understanding by the medical profession where the GP had not been especially supportive, and where contact with the specialist was unsatisfactory. Limited understanding was exacerbated by intervening variables including lack of contact with other FM sufferers and a treatment history focusing on 'fixing' the problem. Men with FM struggled to find meaning in their experience. Some individuals were able to locate possible causes, but all the men were unable to fully understand their condition. The analysis suggested that the experience of FM varies for different men. The study reveals that FM is a complex experience characterised by loss, which sufferers and health care professionals struggle to understand. Implications for health care practice and further research are discussed. This study will help FM sufferers understand their condition more fully. Moreover, it should enrich the understanding of health care professionals - thereby facilitating encounters characterised by greater support and empathy for men with FM.