The Swedish Cancer Register was used to determine the relative survival rate in colon and rectal cancer and to estimate the occurrence of second cancers related to radiation therapy for rectal cancer. The Swedish Hospital Discharge Register and hospital records were used to estimate the rate of late adverse effects due to radiation therapy for rectal cancer. The whole Swedish population was the source of the survival studies. Patients participating in the Uppsala Trial and the Swedish Rectal Cancer Trial on radiation therapy for rectal cancer constituted the subjects of the studies on late adverse effects and second cancers. The main results of the survival analysis revealed a significant improvement in the 5-year relative survival rate for both colon and rectal cancer. During the time period 1960-1999, the survival improved from 39.6% to 57.2% in colon cancer and from 36.1% to 57.6% in rectal cancer. Patients irradiated for rectal cancer, in addition to surgery, were at increased risk for a second cancer compared to those treated by surgery alone. This risk increase was mainly found for cancers developing in organs within or adjacent to the irradiated target (relative risk (RR) 2.04; 95% confidence interval (CI) 1.10–3.79). Furthermore, the most important late adverse effects of radiation therapy seem to be those on the gastrointestinal tract, in the form of small bowel obstruction (RR 1.88; 95%CI 1.10–3.20) and abdominal pain (RR 1.92; 95% CI 1.14–3.23). Overall, the benefit of radiation therapy was greater than its drawbacks, as a large reduction in local recurrences and better survival was noted in patients treated preoperatively with irradiation for rectal cancer. In conclusion, significant improvements in the survival of patients with colon and rectal cancers have occurred in the last decades, especially in patients with rectal cancer. These improvements probably are related to advances in surgical and adjuvant treatment. The radiation therapy has several drawbacks, however, including an increased risk of second cancers and of bowel obstruction. This emphasises the need to further improve the radiation technique and to select only those patients for radiation therapy who are most likely to benefit from it.

The newly established Swedish Apheresis Registry makes it possible to do national inter-center comparisons. This study was undertaken to describe and analyze the use of therapeutic apheresis and the adverse effects in such therapy. The special case of plasma exchange as rescue therapy in multi-organ failure, including renal failure, was also studied. In Sweden, plasma for transfusion is prepared and stored to ensure rapid availability. Due to new EU legislation, validation of such plasma was performed. The analysis indicated that the use of therapeutic apheresis was in line with recommendations of other international societies. The frequency and types of adverse effects were comparable to those reported in other studies from analogous time periods. Compared with other countries, it appears that more therapeutic resources are available in Sweden and that there is a lower frequency of adverse effects in specific procedures. No fatalities were reported. The unique comparison of differences between centers regarding plasma exchange identified areas for further improvement. The study on plasma exchange as rescue therapy in severe sepsis or septic shock is the second largest reported. The result was promising, with a survival rate of 82%. The rapid availability of plasma for transfusion appears to be of clinical importance in patients with early coagulopathy and severe trauma but the present selection and storage procedures for plasma lead to a time-dependent increase of the number of units with cold-induced activation of the contact system and C1 inhibitor consumption before day 14. Improvements of plasma quality can be attained by using plasma from male donors only and by reducing the storage time from 14 to 7 days. Further studies are needed to define the role of plasma exchange in severe sepsis/septic shock, to evaluate the outcome of each patient’s treatment and to establish the indications for the transfusion of plasma.

Physicians are familiar with organophosphates (OPs) as a classic, though obscure, cause of cholinergic poisoning. Many opportunities for human exposure existsixty million pounds of OPs are applied as insecticides to sixty million acres of U.S. land each year, and, until recently, over one-fifth of Americans used these chemicals in their homes. Most physicians, however, still know little about the dangers that these pesticides pose to the developing nervous system. By the late 1980s, toxicologists increasingly recognized that toxicants such as lead and mercury, even at doses well-below the level required to cause symptomatic poisoning, could induce subtle, yet permanent, neurological deficits if the exposure occurred during critical periods of brain development. In the early 1990s, scientists and regulators began to realize that developmental neurotoxicity (DNT), as this phenomenon was called, could also result from OPs. In 1996 Congress passed the Food Quality Protection Act (FQPA), marking a major turning point in the regulation of hazardous chemicals. Prior to the FQPA, the Environmental Protection Agency (EPA) based its calculations of pesticide risk on adults and largely neglected the increased susceptibility of infants and children. The new law took a precautionary stance, protecting the vulnerable neural and physical development of the fetus and child with the inclusion of a 10-X safety factor, and shifting the burden of proof from health advocates to the pesticide manufacturers. The ensuing ten-year battle between health groups, pesticide manufacturers, and the EPA over the laws enforcement now provides an instructive lesson into the complex scientific, political, and economic world of environmental health, and serves as a relatively successful example of effective policy improving public health.

Coronary artery disease (CAD) is the most prevalent disorder and the leading cause of death worldwide. There are a number of CAD medications, which are effective and safe in most patients, but have been associated with adverse reactions such as angioedema induced by angiotensin I-converting enzyme inhibitors (AE-ACEi). In this study, we identified aminopeptidase P (APP) activity as an endophenotype for AE-ACEi, which is a heritable quantitative trait (heritability =0.336 +/- 0.251 SD) and is significantly reduced in a majority of our cases. Although initial mutation screening did not reveal any coding variants in XPNPEP2, which encodes membrane-bound APP, subsequent linkage analysis of APP activity in eight families provided a maximum LOD score (3.75) for this locus. Sequencing of additional cases identified a splice variant (314_431del) and a non-coding polymorphism (rs3788853) in this locus, which cosegregate with low plasma APP activity. The latter accounts for the linkage signal and is associated with AE-ACEi (P = 0.036). In addition, we identified other potential loci for APP activity and demonstrated that certain ACEi (Captopril and Enalapril) non-specifically inhibit APP activity. Furthermore, we detected polymorphisms associated with reduced APP and ACE activities among females with estrogen-dependent inherited angioedema. / We also conducted a genetic investigation of depression among CAD patients to identify common susceptibility loci which might explain the correlation between these diseases. Our candidate gene association study identified a polymorphism (rs216873) in the von Willebrand factor gene that was significantly associated (P = 7.4 x 10-5) with elevated depressive symptoms in our CAD cohort. These results suggest that risk factors for atherosclerosis also underlie susceptibility to depression among CAD patients. / This dissertation contributes to the field of genetics and pharmacogenomics of CAD. A better understanding of the toxic effects of CAD drugs will assist in the development of safer and more effective treatments. In addition, our results may facilitate clinical assays to identify individuals who are susceptible to angioedema prior to ACEi or estrogen therapy. Finally, our genetic investigation of depression in CAD patients reveals a novel drug target (VWF) for treatment of depression in cardiac cases.

Social Anxiety Disorder (SAD) is a mental disorder with high prevalence but low treatment accessibility. A way to facilitate care to these patients is through Internet based treatment. As is the case of most psychological treatments, much has been studied about positive effects but there is a gap regarding adverse effects. This study seeks to fill this gap in the case of an Internet delivered treatment. From a total of 127 participants who took part in a treatment that combined attention biased modification (ABM) and Internet based cognitive behavior therapy (iCBT), 21 (16.5%) presented adverse effects. Most of the adverse effects were detected after participants had received iCBT (13.4%), and these were mostly related to deterioration of symptoms (5.5%), negative wellbeing (3.9%) and emergence of new symptoms (1.6%). Perceived side effects after attention training were less common (4.7%). A thematic analysis showed also that the techniques used in treatment, the lack of time to complete treatment and becoming aware with the impairments of the disorder and its consequences could influence the emergence of adverse effects.

Background: During the past 5 decades, hormone replacement therapy (HRT) has been used, and appreciated for its beneficial effects, by millions of women in their menopause. As treatment for climacteric symptoms, estrogen is outstanding, and effects on hot flushes, vaginal dryness, and insomnia have been widely documented. The increased risks of venous thrombosis and breast cancer, however, restrict the use of estrogen. Estrogen treatment in women with a remaining uterus includes a progestin, added to protect the endometrium from hyperplasia and malignancies. The long-standing clinical impression, that progestin addition negatively influences mood, has been discussed in previous studies. Mood deterioration is, however, not mortal, although mood is important to the wellbeing and daily functioning of women treated with hormones. Studies of the mental side effects of HRT add to our understanding of steroid effects in the brain. Aims and methods: In our studies, we aimed to establish to what extent negative side effects cause women to discontinue HRT, and find out which drug compounds lead to mood deterioration. The questions asked were whether the type and dose of progestin and the estrogen dose during the progestin addition influence the mood and physical symptoms during sequential HRT. Compliance with HRT and reasons for discontinuing the therapy were evaluated in a retrospective longitudinal follow-up study. Treatment effects were studied in three randomized, double-blind, cross-over trials. During continuous estrogen treatment, effects of sequential addition of a progestin were studied by comparing two different progestins, medroxyprogesterone acetate (MPA) andnorethisterone acetate (NETA), comparing different doses of the same progestin, MPA, and comparing two doses of estrogen during addition of the same dose of MPA. The main outcome measure was the daily rating on mood and physical symptoms kept by the participants throughout the studies. The clinical trials were carried out at three gynecological centers in northern Sweden. Results and conclusions: Besides fear of cancer and a wish to determine whether climacteric symptoms had meanwhile disappeared, negative side effects was the most common reason or discontinuing HRT. Tension in the breasts, weight gain, a depressed mood, abdominal bloating, and irritability were the most important side effects seen both in women who continued HRT and in women who had discontinued the therapy. In our clinical trials, we showed that addition of a progestin to estrogen treatment induces cyclic mood swings characterized by tension, irritability, and depression, as well as increased breast tension, bloatedness, and hot flushes. Women with a history of premenstrual syndrome (PMS) appeared to be more sensitive to the progestin addition and responded with lower mood scores compared with women without previous PMS. In our studies, MPA provoked depressed mood to a lesser extent than did NETA. Surprisingly, the higher dose of MPA (20 mg) enhanced the mood, compared with 10 mg, when added to estrogen treatment. In women continuously treated with 3 mg estradiol, mood and physical symptoms worsened during the progestin addition, as compared with treatment with 2 mg estradiol. The negative side effects seen during sequential HRT have much in common with symptoms seen in the premenstrual dysphoric disorder (PMDD), which is a psychoneuroendocrine disorder with psychiatric expression. Explanations for treatment effects on mood are likely to be found in drug interactions with neurotransmitter systems of the brain. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 2003</p> / digitalisering@umu

Bakgrund Ventilatorbehandling kan orsaka lidande i form av bland annat Ventilator Associerad Pneumoni (VAP) och delirium. Att avsluta behandlingen för tidigt kan också orsaka lidande och därför är tydliga kriterier för att verifiera urträning och extubation, borttagande av ventilatorn och endotrakealtuben är viktiga aspekter i vården och omvårdnaden av patienten. Syfte Syftet med studien var att identifiera kriterier för att verifiera lyckade eller misslyckade urträningar och extubationer hos intensivvårdspatienter och att undersöka vilka bedömningsprotokoll för detta som används. Metod Metoden har varit en (deskriptiv) litteraturöversikt med systematisk ansats. Sökning har gjorts i databasen PubMed. Vid sökningen hittades 627 artiklar och av dessa inkluderas 17 artiklar i studien. Resultat Resultatet visar att det finns flera kriterier för att verifiera lyckade eller misslyckade urträningar och extubationer, men de mest uttalade kriterierna var, hemodynamisk status, inställda/uppmätta ventilatorvärden, blodgasvärden, det mentala/neurologiska tillståndet hos patienten och spontant andningstest (SBT). Slutsats Kriterier och dess protokoll är viktiga redskap för vårdpersonalen för att avgöra när det är dags att börja urträning och förbereda för extubation av den ventilatorbehandlade patienten. / Background Mechanical ventilation can cause suffering in the form of, among other things Ventilator Associated Pneumonia (VAP) and delirium. Stopping treatment too early may also cause suffering and therefore clear criteria to assess extubation withdrawal and weaning of the ventilator are important aspects in the care and nursing of the patient. Purpose The purpose of the study was to identify criteria for verifying successful or unsuccessful weaning and extubations in ICU patients and to investigate assessment protocol. Method The method has been a descriptive literature review with a systematic approach. Conclusion The result shows that there are several criteria to verify successful or unsuccessful weanings and extubations, but the most explicit criteria were - hemodynamic status, set / measured values for the mechanical ventilations, blood gas status, mental / neurological state of the patient and spontaneous breathing test (SBT). Criteria and subsequent protocols are important tools for caregivers to determine when it is time to start weaning and prepare for extubation.

The present thesis explores the relationship between occupational rhinitis and occupational asthma under the postulates of the "united airways disease" concept that refers to the multiple links observed between rhinitis and asthma. Accordingly, the main objective of this thesis is to demonstrate the concomitant expression of significant changes in nasal patency and bronchial calibre following exposure to occupational agents during specific inhalation challenges, complementing the assessment with the investigation of changes in markers of airways inflammation in nasal lavage. To achieve the objectives, we set up a protocol to diagnose occupational rhinitis and conducted a study from January 2005 to January 2007 at Hopital du Sacre-Coeur de Montreal in subjects undergoing investigation for occupational asthma. The reliability of the main research tools---acoustic rhinometry and nasal lavage---used to investigate occupational rhinitis was tested by analyzing the reproducibility of the methods. Both methods proved sufficiently reproducible to be included in our investigative protocol. The results presented in this thesis demonstrate a joint reaction of the nose and the lungs in a group of study subjects after performing specific inhalation challenge. This supports the concept of a "united airways disease" and its applicability to rhinitis and asthma of occupational origin. However, the results also show that although occupational rhinitis frequently coexists with occupational asthma it can also be present without occupational asthma. The assessment of upper airways inflammation in a subgroup of study subjects by the nasal lavage method allows us to observe significant changes in eosinophils counts after the challenge that correlates with the decrease in nasal patency observed in the same subjects.

Diss. (sammanfattning) Linköping : Univ. / Härtill 6 uppsatser.

Diss. (sammanfattning) Linköping : Univ., 2001. / Härtill 5 uppsatser.