The objectives of this case-control study, investigating 51 in-patient women with acute pelvic inflammatory disease (PID) and 50 healthy women attending for routine gynecological check-up, were to investigate the background and reproductive history of women, who are considered at low risk of sexually transmitted infection presenting with PID, to examine whether intrauterine device (IUD) use per se and long use affects the microbiology and clinical course of the disease, to identify risk factors for PID and to examine whether IUD use is an independent risk factor for PID. The most striking difference regarding the background and reproductive history between women with PID and healthy women over age 25 were related to socio-demographic factors and not to common risk factors for PID. There was little difference between healthy women and women with current PID with regard to single microbes. The finding of combinations of several anaerobic or aerobic/anaerobic microbes appeared to be associated with PID, particularly in women over 35. The pathogenesis of non-sexually transmitted PID appears to be associated with a synergistic effect between several pathogens, possibly facilitated by the presence of an IUD. IUD use per se was associated with an increased risk of PID in women 35 and older. There was an association between IUD use and complicated PID in women over 35, which was possibly influenced by long-term IUD use. Age over 35 and IUD use, independently of each other, were associated with an increased risk of failed conservative treatment, necessitating surgery in patients with PID. An observational study showed that Latvian obstetrician-gynecologists participate actively in contraceptive counseling and are very experienced with regard to IUD use. Physicians’ attitudes and perceptions towards IUD are generally positive and their clinical considerations are in good agreement with that of doctors in other countries. Antibiotics are widely used around IUD insertion by doctors, possibly driven by a liberal attitude towards IUD use in women with a potential risk of STI. The study could identify some possible gaps in the theoretical knowledge about the IUD and other methods.

<p>We treated 16 patients with somatostatin analogs combined with α-interferon and achieved a biochemical and/or radiological response in 56% (median duration 22 months). We consider this treatment a good alternative for patients who fail during chemotherapy or who do not want to/cannot receive cytotoxic drugs.</p><p>Thirty-six patients with neuroendocrine tumors were treated with cisplatin combined with etoposide. Of 14 patients with evaluable EPTs, 50% responded radiologically and/or biochemically (median duration 9 months). We consider this treatment useful as first-line medical treatment in aggressive EPTs or in patients failing prior chemotherapy.</p><p>Twenty-eight tumor tissues from EPTs were examined with immunohistochemistry regarding expression of somatostatin receptors (ssts) 1 to 5 on tumor cells and in intratumoral vessels. We found that sst₂ and sst₄ were highly expressed on tumor cells and in vessels. However, sst₃ and sst₅ were lacking in half of the tumor tissues and in most of the vessels. Because of the variability in sst expression, we recommend analysis of each individual’s receptor expression before starting treatment.</p><p>Endocrine pancreatic tumors (EPTs) are rare with an incidence of 4 per million inhabitants. In the majority of cases they grow slowly, but there are exceptions with very rapidly progressing malignant carcinomas. First-line medical treatment is streptozotocin combined with 5-fluorouracil.</p><p>We examined 38 tumor samples regarding expression of tyrosine kinase receptors platelet-derived growth factor receptors (PDGFRs), c-kit and epidermal growth factor receptor (EGFR). We found that the receptors were expressed in more than half of the tumor tissues. Further studies will reveal if tyrosin kinase antagonists can be part of the future treatment arsenal.</p>

We treated 16 patients with somatostatin analogs combined with α-interferon and achieved a biochemical and/or radiological response in 56% (median duration 22 months). We consider this treatment a good alternative for patients who fail during chemotherapy or who do not want to/cannot receive cytotoxic drugs. Thirty-six patients with neuroendocrine tumors were treated with cisplatin combined with etoposide. Of 14 patients with evaluable EPTs, 50% responded radiologically and/or biochemically (median duration 9 months). We consider this treatment useful as first-line medical treatment in aggressive EPTs or in patients failing prior chemotherapy. Twenty-eight tumor tissues from EPTs were examined with immunohistochemistry regarding expression of somatostatin receptors (ssts) 1 to 5 on tumor cells and in intratumoral vessels. We found that sst2 and sst4 were highly expressed on tumor cells and in vessels. However, sst3 and sst5 were lacking in half of the tumor tissues and in most of the vessels. Because of the variability in sst expression, we recommend analysis of each individual’s receptor expression before starting treatment. Endocrine pancreatic tumors (EPTs) are rare with an incidence of 4 per million inhabitants. In the majority of cases they grow slowly, but there are exceptions with very rapidly progressing malignant carcinomas. First-line medical treatment is streptozotocin combined with 5-fluorouracil. We examined 38 tumor samples regarding expression of tyrosine kinase receptors platelet-derived growth factor receptors (PDGFRs), c-kit and epidermal growth factor receptor (EGFR). We found that the receptors were expressed in more than half of the tumor tissues. Further studies will reveal if tyrosin kinase antagonists can be part of the future treatment arsenal.

Actinobacillus actinomycetemcomitans is present in elevated proportions and numbers in dental bacterial biofilms of patients with localized aggressive periodontitis. This variant of periodontal disease, occurring in adolescents and young adults, is characterized by rapid and severe destruction of the connective tissues and bone supporting the teeth, eventually culminating in tooth loss. The cytolethal distending toxin (Cdt) is a newly discovered bacterial protein toxin, uniquely present in A. actinomycetemcomitans among all known to-date oral bacterial species. The Cdt has the capacity to inhibit mammalian cell growth, but its putative role in the pathogenesis of the disease is unclear. The aim of this in vitro work has been to study the effects of A. actinomycetemcomitans on periodontal connective tissue cell cultures, and to evaluate the possible involvement of its Cdt. A. actinomycetemcomitans inhibited the proliferation of gingival and periodontal ligament fibroblasts, as a result of a combined arrest at the G1 and G2/M phases of the cell cycle. This growth inhibition was non-lethal and the cells remained metabolically active, although their DNA synthesis was reduced. The intoxicated cells exhibited increased size and irregular structure, characterized by distension and elongation. This cellular enlargement occurred in both G1 and G2/M phase arrested cells. The Cdt of A. actinomycetemcomitans was responsible for the observed growth inhibition, as well as the concomitant morphological alterations. The possible induction of inflammatory cytokines related to bone resorption was investigated in response to A. actinomycetemcomitans, and the involvement of Cdt was evaluated. Extensive focus was given to the study of receptor activator of NF-κB ligand (RANKL) expression, a membrane-bound ligand that signals osteoclast progenitors to differentiate and fuse into mature osteoclasts, activating bone resorption. It was demonstrated that A. actinomycetemcomitans induced RANKL mRNA and protein expression in the cells studied, but did not affect the expression of its decoy receptor, osteoprotegerin. This induction was solely attributed to its Cdt, as demonstrated by the use of a cdt-knockout A. actinomycetemcomitans strain, purified recombinant Cdt, and antibodies blocking the Cdt. In addition, this event was not mediated by pro-inflammatory cytokines known to stimulate RANKL. Interleukin-6 mRNA and protein expression were also enhanced by A. actinomycetemcomitans, but Cdt had limited involvement in this enhancement. In conclusion, two distinct mechanisms by which A. actinomycetemcomitans Cdt may be involved in the pathogenesis of localized aggressive periodontitis are proposed. Firstly, the growth arrest of the resident fibroblasts may impair the physiological connective tissue remodelling equilibrium and lead to connective tissue attachment loss. Secondly, the induction of RANKL by these cells, residing in the proximity of the alveolar bone, may locally stimulate osteoclastogenesis and promote alveolar bone resorption. This work also provides further insights to the understanding of Cdt mechanisms of action, contributing to the global characterization of the toxin’s virulence.

The occupational exposures of sewage workers are complex and variable, and include a great variety of biological and chemical agents. Previous research has focused mostly on infections and various symptoms among sewage workers, e.g. abdominal and respiratory symptoms. At several sewage plants in Sweden, concern arose about occupational cancer, specifically cancer of the stomach, the kidney, and the lung. The aim of this study was to study the cancer incidence among municipal sewage workers, some exposures that might be connected with cancer risk, and self reported abdominal and respiratory symptoms. In a cohort of municipal sewage workers there was no increase in the overall incidence of cancer when compared with the general population. However, there was a slight increase in the incidence of prostate cancer, but not in the sites of original concern among the workers. Infection by the gastric carcinogen Helicobacter pylori (determined from the presence of IgG antibodies in serum against H pylori) was no more prevalent in sewage workers than in comparable referents. Neither were sewage workers more exposed to genotoxic agents than comparable referents, as measured by the alkaline single cell gel electrophoresis (SCG) assay performed on peripheral lymphocytes. There was no increase in the three-month prevalence of abdominal symptoms when compared with other municipal workers. Specifically, there was no difference in prevalence of the common disorders dyspepsia and irritable bowel syndrome. Sewage workers reported adult bronchial asthma significantly more than the referents.

Traumatic brain injury (TBI) is a major cause of mortality and disability. As common sequelae in survivors of TBI are disabling functional, emotional and cognitive disturbances, improved treatment of TBI patients is urgently needed. At present, no neuroprotective pharmacological treatment exists. The formation of oxygen-centered free radicals, reactive oxygen species (ROS), is considered an important event in the pathophysiology of TBI. In the present thesis, the fluid percussion (FPI) and controlled cortical contusion injury models of TBI in rats were used. Two nitrone radical scavengers, α-Phenyl-N-tert -butyl nitrone (PBN) and the sulfonated analogue of PBN, 2-sulfophenyl-N-tert-butyl nitrone (S-PBN), were used as tools to study the role of ROS in TBI. Pre-treatment with PBN (30 mg/kg) improved morphological and cognitive outcome after severe controlled cortical contusion injury. Treatment with equimolar doses of PBN and S-PBN administered 30 min after FPI followed by a 24 h intravenous infusion improved morphological outcome. Only S-PBN improved cognitive outcome as assessed in the Morris Water Maze. Surprisingly, pre-treatment with PBN increased the number of apoptotic neurons at 24 hours after injury despite a reduced lesion volume. FPI resulted in an early increase in glucose uptake and a reduction in regional cerebral blood flow (rCBF) assessed by fluoro-2-deoxyglucose (FDG) and hexamethylpropylene amine oxime (HMPAO) autoradiography. At 12 h, a marked reduction in glucose uptake and rCBF ensued. These TBI-induced changes were attenuated by PBN and S-PBN pre-treatment. A method for ROS detection using 4-hydroxybenzoate in conjunction with microdialysis was evaluated. The results showed a marked increase in ROS formation as assessed by an increase in the single adduct 3,4-DHBA, lasting 90 min after injury. In a separate study, PBN and S-PBN equally reduced 3,4-DHBA formation despite no detectable brain concentrations of S-PBN at 30 or 60 min post-injury. In conclusion, ROS play an important role in the injury process after TBI. We report a method for ROS detection with potential clinical utility. Nitrones increased ROS elimination and improved functional and morphological outcome. Nitrone treatment may have a clinical potential as a neuroprotective concept in TBI.

Oral and pharyngeal cancer is commonly treated with a combination of radiotherapy and surgery. It is a clinical knowledge that patients often experience severe swallowing disorders following treatment. Since surgical sequelae are instantaneous and obvious, little attention has been paid to other concurrent effects of the treatment. To shed light on this subject, the aim of this thesis was twofold (i) to make a retrospective inventory of the sequelae following treatment and (ii) to perform a prospective, inceptive examination at diagnosis, and to follow-up after radiotherapy, six months and 12 months after surgery. The files of ninety-nine patients revealed that following treatment one-third had to use gastric fistulas and more than nine of ten patients had restricted swallowing capacity. Every second patient could only swallow puréed or liquid food. Adequate intra-oral sensation and discrimination ability is essential for bolus preparation and bolus control, for appropriate elicitation of the swallowing reflex and, hence, for the oral phase of swallowing. At the inceptive examination, the prospective part of the study demonstrated intra-oral discrimination ability in patients was equal to that in healthy controls but was impaired six months after treatment and there was no significant improvement after 12 months. It had been expected that the patient’s healthy, non-tumor side would compensate but it did not. An explanation was found when it was revealed that radiotherapy induced a delayed decline in intra-oral sensation. Sensory decline was not demonstrated within a month after radiotherapy but was manifest six months later. Since the radiotherapy field includes the neck, because of the risk for metastasis, it is highly plausible that pharyngeal sensation declines in a manner corresponding to that found intra-orally when the healthy side is irradiated. In accord with this presumption, pharyngeal swallowing function deteriorated in patents with oral tumors. Cineradiographic evaluation of oral and pharyngeal swallowing function disclosed a significant association between the degree of swallowing dysfunction and the degree of sensory decline and with the degree of impairment of shape recognition. Conclusions: Delayed intra-oral sensory decline, found to be induced by radiotherapy, can be expected to appear in the entire radiation field, including the oral cavity and the pharynx, with adverse effect on swallowing. Testing intra-oral sensation close to the last radiotherapy session is not advisable, because sensory decline does not develop immediately after radiotherapy but manifests after six months. Spontaneous sensory rehabilitation cannot be expected after six months. The significant association between degree of swallowing dysfunction and degree of intra-oral sensory decline and impaired discrimination ability must be considered in the quest for functional rehabilitation of patients treated for oral or pharyngeal cancer.