Bakgrund: En av sjuksköterskans grundläggande uppgifter är att lindra patientens lidande i samband med vård. Lugn musik har visat sig vara ett effektivt verktyg för att minska patienters upplevelser av stress och smärta vid flera procedurer inom sjukvården. Parametrar som hjärtfrekvens och blodtryck kan påverkas av musiken. Frisättning av hormoner och signalsubstanser kan minska patientens känslor av obehag av olika slag. Venös blodprovtagning utförs rutinmässigt på vårdcentraler över hela landet. Inom primärvården saknas dock riktlinjer för hur lugn musik kan användas för att öka patientens välmående i denna vårdsituation.  Syfte: Denna studies syfte var att undersöka huruvida lugn bakgrundsmusik påverkar patienters skattning av stress och smärta i samband med venprovtagning på vårdcentral samt att undersöka skillnader i skattning av stress och smärta vid venprovtagning beroende av patientkarakteristika.  Metod: En kvantitativ interventionsstudie med enkätundersökning på vårdcentral genomfördes. Frågeformulär delades ut direkt efter provtagningstillfället till 70 patienter. Av dessa hade 35 exponerats för lugn bakgrundsmusik under proceduren och 35 fått venprovet genomfört utan musik.  Resultat: Inga signifikanta skillnader kunde påvisas mellan musikinterventionsgruppen och kontrollgruppen. Signifikanta skillnader kunde påvisas i skattning av stress och smärta mellan patienter relaterat till åldersgrupp där yngre patienter skattade stress och smärta högre än äldre patienter. Mellan manliga och kvinnliga patienter kunde en signifikant skillnad i smärtskattning påvisas där kvinnor skattade högre än män. De patienter som uttryckte stickrädsla skattade stress och smärta högre än övriga patienter. Ingen skillnad i skattning av stress eller smärta kunde påvisas mellan de patienter som ansågs vana och de som ansågs ovana vid venprovtagning.  Slutsats: Ingen signifikant skillnad i skattning av stress och smärta relaterat till bakgrundsmusiken i interventionen kunde genom denna studie påvisas. Mot bakgrund av tidigare forskning kan dock tänkas att mer omfattande studier på samma ämne kan leda till ett annat resultat. Majoriteten av de fynd som relaterades till patientkarakteristika verkar stämma överens med tidigare forskning. / Background: One of the basic tasks of the nurse is to alleviate the patient’s suffering associated with health care. Relaxing music has proven to be an effective tool to reduce patients’ experiences of stress and pain during many health care procedures. Parameters as heart rate and blood pressure can be affected by the music. Release of hormones and signal substances can reduce the patient’s feelings of different kinds of discomfort. Venous blood sampling is performed as a routine at health care centers across Sweden. In primary health care there are no guidelines on how relaxing music can be used to increase the patient’s well-being in this care situation.  Aim: The aim of this study was to investigate whether relaxing background music has an impact on the health center patient’s grading of stress and pain during venipuncture, and to examine differences in grading of stress and pain during venipuncture dependent on patient characteristics.  Method: A quantitative intervention study with a survey at a health center was performed. Questionnaires were distributed immediately after venous blood sampling to 70 patients. Of these, 35 had been exposed to relaxing background music during the venipuncture, and 35 had not been exposed to any music during the procedure.  Main results: No significant differences were found between the music intervention group and the control group. Significant differences were found in grading of stress and pain between patients dependent on their age group, younger patients ranked their stress and pain higher than older patients. Between male and female patients a significant difference in grading of pain were found, women ranked their pain higher than men. The patients who expressed a fear of needles ranked their stress and pain higher than other patients. No difference in grading of stress or pain could be found between those patients who were considered accustomed, and those who were not considered accustomed to venipuncture.  Conclusion: No significant difference in grading of stress and pain could be found related to the music intervention in this study. Based on previous studies, there is still a possibility that more extensive research on the same topic can produce a different result. The majority of findings related to patient characteristics seems to be aligned with previous research in this field.

Background: Primary aldosteronism (PAL) has emerged as the commonest specifically treatable and potentially curable form of secondary hypertension. With its propensity towards cardiovascular complications above that expected from hypertension alone, PAL is a potentially highly detrimental state which should be detected as early as possible in the course of the disease and treated appropriately. The detection of earlier, milder, normokalaemic forms of PAL using the aldosterone/renin ratio (ARR) as a screening test has significantly enlarged the clinical spectrum of PAL and facilitated identification of a new familial variety (familial hyperaldosteronism type II, FH-II). Unlike familial hyperaldosteronism type I (FH-I), FH-II is not glucocorticoid remediable and is not caused by the CYP11B1/CYP11B2 “hybrid” gene mutation. The genetic defects underlying FH-II have not yet been elucidated and hence, detection of FH-II still involves complicated and time-consuming biochemical screening by ARR testing and confirmation by carefully performed suppression testing such as fludrocortisone suppression testing. Diagnosing PAL by currently available biochemical methods is tedious. Finding a simple and reliable genetic test for FH-II which could be applied to all members of a family with known FH-II and also to apparently sporadic PAL would simplify patient management. A genome-wide search has already demonstrated linkage of FH-II to chromosome 7p22, consistent with this locus harbouring the causative gene/s for FH-II. Three candidate genes [retinoblastoma-associated Kruppel-associated box gene (RBaK, involved in tumorigenesis and cell cycle control), postmeiotic segregation increased 2 (PMS2, involved in DNA mismatch repair and tumour predisposition) and guanine nucleotide-binding protein alpha-12 (GNA12, a transforming oncogene)] within this linked locus have been examined in an attempt to find the causative mutations for FH-II, but no clear causative mutations have so far been found. PAL continues to be a challenging yet rewarding disease to manage. Although much has been learnt about PAL, there are still many areas which have not been explored. PAL considered due to bilateral autonomous production of aldosterone is usually treated medically because unilateral adrenalectomy has been considered ineffective. Since medical treatment may cause adverse effects or fail to control hypertension, defining the role of unilateral adrenalectomy in bilateral PAL is an important clinical issue, but quality outcome data are lacking. The candidate therefore peformed a retrospective study of the efficacy of unilateral adrenalectomy in patients with bilateral PAL. In patients with unilateral PAL, unilateral laparoscopic adrenalectomy has been shown to correct hypokalaemia and lead to cure or improvement in hypertension control. While most studies have focused on clinical and biochemical outcomes, to the candidate’s knowledge, there are no data on the effects of adrenalectomy on quality of life (QOL). Assessing the QOL in patients with unilateral PAL before and after unilateral laparoscopic adrenalectomy (which cured hypokalaemia in all and hypertension in the majority) provided an insight into the degree to which the disease process and/or its treatment affects the life of an individual with PAL. Aims: The overall aims of this thesis were to further explore the genetic basis of FH-II, to examine the role of adrenalectomy in patients with bilateral PAL and the effects of unilateral adrenalectomy on QOL in unilateral PAL as a first step in dissecting out the effects of medical and surgical treatment on QOL in the more common bilateral PAL. In order to address the overall aims, the specific aims of the thesis were (1) to narrow the linked region at 7p22 by phenotyping and genotyping additional FH-II families from Italy, using more closely spaced microsatellite markers at 7p22, and then assess the combined multipoint logarithm of odds (LOD) score for these Italian as well as two Australian and one South American families; (2) to sequence candidate genes in the narrowed linked region for FH-II associated mutations; (3) to assess the role of unilateral adrenalectomy in bilateral PAL and identify predictive parameters; and (4) to assess the quality of life following unilateral adrenalectomy in patients with unilateral PAL. Methods and Results: Two Italian families with FH-II were genotyped using seven closely spaced microsatellite markers at 7p22. All known affected individuals from each of the two Italian families were found to share identical haplotypes for the seven markers, consistent with linkage of the disease locus with the 7p22 region. The multipoint LOD score of the now five known families with FH-II which demonstrate linkage at 7p22, calculated using MERLIN linkage analysis was highly significant at 5.22. Three candidate genes in this linked region were then examined for mutations causing FH-II; the replication protein A 3 (RPA3), zinc finger protein 12 (ZNF12) and glucocorticoid induced transcripts 1 (GLCCI1) genes were selected as they are involved in cell cycle control, and adrenal hyperplasia and adenomas are common in FH-II. Using the method of polymerase chain reaction-sequencing, coding regions, splice sites, proximal promoter, 5’ and 3’ untranslated regions (UTR) were sequenced in affected and unaffected subjects from the 7p22-linked FH-II families. Identified single nucleotide polymorphisms (SNPs) were genotyped to assess significance. For RPA3, four different SNPs were initially found to segregate with the affectation status, that is, they were present in the two affected and not the two unaffected subjects from the largest Australian family (family 1, eight affecteds) with FH-II. However, only two SNPs (rs2024374 G/C and rs17169194 T/G) were further genotyped as that they were in functionally important positions of the gene (that is, in regulatory regions within the promoter and 5’ UTR) and because of the relatively low allele frequency reported in the literature for these two SNPs in controls. Further genotyping of these SNPs was carried out in another six affecteds and four unaffecteds from the same family and a complete segregation of these two SNPs with affectation status was seen in family 1. The G/C mutation rs2024374 in the RPA3 promoter results in the loss of three transcription factor binding sites and creation of one new site. The factors for which the binding sites in the RPA3 promoter and 5’UTR were altered by these two SNPs were involved in regulation of cell differentiation, proliferation and apoptosis. Hence, it is possible that altered activity of the RPA3 promoter and 5’UTR in family 1 could result in predisposition to adrenal hyperplasia or neoplasia, altered ARR and/or hypertension. Genotyping of these SNPs was then carried out in another two pedigrees (families 2 and 3) that showed linkage to 7p22, and in 75 normotensive, non-PAL control subjects. However, neither of these two SNPs segregated with the affectation status in family 2 and 3, and they were present in 30% and 20% of controls, respectively. For ZNF12 and GLCCI1, no evidence of causative mutations was found in the coding regions, splice sites, proximal promoter region and proximal 5’ and 3’ UTR. Between 1984 and 2004, 51 of 684 patients diagnosed with bilateral PAL underwent unilateral adrenalectomy. Forty patients fulfilled the inclusion criteria and were followed for at least 12 (median 56.4) months. Hypertension was cured in 15% and improved in 20%, usually within one year of unilateral adrenalectomy. The proportion with controlled hypertension was significantly (p<0.001) higher after adrenalectomy (65%) than before (25%). Mean systolic (p<0.001) and diastolic (p<0.001) blood pressure, left ventricular mass index (p<0.05) and aldosterone/renin ratio (p<0.001) fell. Serum creatinine independently predicted hypertension cure. From 2007 through 2008, QOL was evaluated prospectively using the internationally validated SF-36 questionnaire before and 3 and 6 months post-operatively in 22 patients [14 males, 8 females; mean age 50.0 ± 2.0 (range 27-69) years] with unilateral PAL who underwent adrenalectomy within the Endocrine Hypertension Centre, Greenslopes and Princess Alexandra Hospitals. Pre-operatively, the SF36 score for each QOL domain was lower for PAL patients than reported for the Australian general population, significantly so for physical functioning (p<0.05), role physical (p<0.001), vitality (p<0.001) and general health (p<0.05). Compared with pre-adrenalectomy, there were significant increments in mean scores at 3 months for physical functioning (p<0.05), role physical (p<0.05), general health (p<0.001), role emotional (p<0.05), social functioning (p<0.05), mental health (p<0.001) and vitality (p<0.001); and at 6 months for physical functioning (p<0.05), role physical (p<0.05), general health (p<0.05), role emotional (p<0.05), mental health (p<0.05) and vitality (p<0.001). Mean SBP and DBP improved significantly (p<0.001), with 86% of these patients cured (BP≤140/90, no drugs) and the remaining 14 % improved. Mean plasma potassium (p<0.001) and renin concentration rose (p<0.01), whereas mean upright plasma aldosterone (p<0.001), aldosterone/renin ratio (p<0.001) and number of antihypertensive agents fell (p<0.001). Conclusion: In the Italian families with FH-II available for study, work by the candidate included in this thesis confirmed linkage of FH-II to chromosome 7p22. The combined multipoint LOD score of 5.22 for the five families showing linkage at 7p22 was highly significant. Linkage to 7p22 in Italian families with FH-II extends the previous positive findings to a third geographical area, bringing greater certainty regarding the importance of this locus in identifying causative mutations. Although no clear causative mutations were found in the three 7p22 candidate genes examined, it is conceivable that the rs2024374 G/C and/or rs17169194 T/G SNPs in RPA3 could act in conjunction with another 7p22 mutation in family 1, resulting in the FH-II phenotype. Examination of the outcome of unilateral adrenalectomy in patients with bilateral PAL suggests that this surgical approach can be beneficial in certain carefully selected patients and should not be automatically excluded as a treatment option. Unilateral adrenalectomy in patients with unilateral PAL has positive impacts not only on clinical and biochemical parameters but also on QOL. The findings of this thesis provide new insights into the genetic basis and therapeutic options and treatment outcomes of PAL and further highlight its importance as a common, genetically based, specifically treatable and potentially curable cause of hypertension and cardiovascular disease. It also points the way to potentially very useful studies in future by exploring longer term effects of unilateral laparoscopic adrenalectomy as treatment for PAL on QOL, to compare unilateral adrenalectomy in those with unilateral versus bilateral PAL, and to compare surgery with specific medical treatment.