Bacterial meningitis continues to be a major health problem and despite great advances in antimicrobial therapy the fatality rate remains high. There is increasing evidence that leukocyte-endothelial interactions are involved in CNS damage during bacterial meningitis. Once leukocytes have entered the CSF they cause injury by releasing toxic molecules such as nitric oxide (NO) and reactive oxygen species (ROS). The induction of iNOS was examined by assessing intracerebral mRNA expression and protein production during the course of Haemophilus influenzae type b (Hib) meningitis in the rat. Induction of iNOS mRNA was detected 12h postinoculation (pi), followed by a gradual reduction. The increased number of intracerebral iN OS expressing cells was detected at 12h pi. followed by further elevation to peak expression at 72h pi. The iNOS positive tissue also bound antibodies specific for nitrotyrosine. The expression of iNOS and NO production, as shown by nitrotyrosine expression, correlated with disease severity, suggesting that activation of iNOS may play an important role in Haemophilus irifluenzae type b meningitis.

Acute bacterial infectious diseases are mostly treated empirically at admission before the culture results are available. According to the risk for serious complications in the case of therapeutic failure, it is important to evaluate the therapy results and change to a more appropriate antibiotic regime as soon as possible. In the present study, 40 patients with X-ray-verified community-acquired pneumonia were examined and blood specimens were collected before and within 24 h of treatment. Body temperature, C-reactive protein (CRP) and hepatocyte growth factor (HGF) were investigated. Thirty-two patients received an appropriate initial antibiotic therapy regarding clinical outcome, but in 8 patients the treatment was changed because of therapy failure. Changes of HGF levels after 18–24 h of treatment could predict the therapeutic results accurately in 38 of 40 cases (sensitivity 100%, specificity 94%, positive likelihood ratio 16.0). HGF was significantly better to predict therapy outcome than CRP (p < 0.0001).

Uterine leiomyoma is a very common benign tumour with unclear pathophysiology in adult women. In the present study we have investigated the expression level of α₂- and β₂-adrenoceptors, and the adenylyl cyclase and phosphodiesterase activity in leiomyoma tissue compared with adjacent myometrium. Our results show that the α₂/β₂-adrenoceptor ratio is increased in leiomyoma, due to a significant decrease in β₂-adrenoceptor expression. These changes were not due to an increased innervation, as the tumour tissue was completely devoid of nerve fibres. Moreover, the adenylyl cyclase activity of leiomyoma membranes was found to be ~50% lower, whereas the phosphodiesterase activity was significantly increased (by ~100%). We found that stimulating an increase in intracellular cyclic AMP, by adenylyl cyclase activity through β₂-adrenoceptors (isoprenaline), by direct enzyme activation (forskolin), or by inhibition of phosphodiesterase activity (papaverine), potently blocked both protein and DNA synthesis in cultured leiomyoma smooth muscle cells. Our results imply the adrenoceptors might be involved in, or a consequence of, leiomyoma growth. The results also suggest a new interesting approach for leiomyoma pharmacotherapy.

The aim of the present investigation was to determine which subtypes of the α₂-adrenoceptors are being expressed in the human pregnant myometrium at term pregnancy. In radioligand binding studies, the specific binding of [³H]rauwolscine to human myometrial membranes was specific and of high affinity with K_d of 2.8 ± 0.6 nM and B_max of 95 ± 5 fmol/mg protein. Results from competition for the binding of [³H]rauwolscine using subtype-selective ligands, oxymetazoline (α₂A-subptype), chlorpromazine (α₂B-subtype) and prazosin (α₂B-α₂C-subtype), suggested that the α₂A- and α₂B-subtypes are being co-expressed. In order to examine if also the α₂C-subtype is being expressed we used an optimal concentration of oxymetazoline or chlorpromazine which would block the high-affinity site, equivalent to the α₂A- and α₂B-subtype respectively. Competition curves of both oxymetazoline and chlorpromazine still showed a significantly better fit using a two-site model, suggesting that the α₂C-subtype also is being expressed. The expression of α₂C-subtype mRNA was confirmed using reverse transcription-polymerase chain reaction on mRNA isolated from myometrial biopsies.

In conclusion, our results suggest that all three subtypes of α₂-adrenoceptors are being coexpressed in the human myometrium at term pregnancy and that α₂-expression is dominated by the α₂A-subtype.

In the western world diabetes mellitus is one of the most common severe diseases in childhood, but it is rarely seen in black African populations. However, there are very few epidemiological studies of childhood diabetes in Africa and almost nothing is known of the Nigerian population. One aim of this study was therefore to estimate the prevalence of insulin dependent diabetes (IDDM) in children and adolescents and to characterize their type of diabetes.

A screening of almost 78,000 school children was performed and beside some already known diabetic patients several new cases were diagnosed. It was found that IDDM is much less common than in Europe but on the other hand more common than in several Asian countries. In addition the prevalence found may be underestimated because of cultural and social factors, health care problems and high mortality in diabetes. Although most patients had a clinical picture of Malnutrition Related Diabetes (MRD) we found in some cases autoantibodies towards islet cells and insulin and furthermore the same HLA-DQ-type-associations as seen to Type 1 diabetes in caucasian diabetics.

While we saw no seasonal variation of diagnosis of Nigerian IDDM, there is a pronounced such seasonal variation in Sweden. This study has tried to elucidate whether this seasonal variation is related to any differences in manifestation and clinical course. Patients diagnosed during incidence peaks had more often short duration of symptoms before diagnosis,ketonuria at diagnosis, rapid loss of endogenous insulin secretion but increase of insulin antibodies and of glycosylated haemoglobin. They had also more often infections before diagnosis and high serum immunoglobulins (IgG and IgM) up to 9 months after diagnosis. HLA-DR4 was more common in these patients. The results suggest that IDDM in Swedish children is heterogenous.

Young breast cancer patients have a decreased survival rate and it has been demonstrated that young age is an independent predictor of adverse prognosis. Overexpression of c-erbB-2 protein (also known as HER-2/neu) has been shown to be a prognostic indicator in breast cancer in general and especially among patients with axillary nodal metastases. The present study was initiated to determine the prognostic significance of c-erbB-2 protein overexpression in early onset breast cancer.

A population consisting of 110 young breast cancer patients, ≤ 36-year-old at diagnosis, was analyzed with immunohistochemical staining for c-erbB-2 protein.

Thirty patients (27%) were found to overexpress the c-erbB-2 protein. C-erbB-2 positivity was significantly associated with poor survival when all patients were included in the analysis (P = 0.002) and for patients with axillary nodal metastases (P = 0.0007). No such association was found for node-negative patients. Furthermore, the difference in prognosis in relation to c-erbB-2 among node-positive patients was maintained, when these were stratified in groups treated or not treated with adjuvant chemotherapy.

The study indicates that overexpression of c-erbB-2 protein is a strong prognostic factor in young breast cancer patients with axillary nodal metastases. Moreover, the adverse prognosis associated with c-erbB-2 overexpression in node-positive patients was observed whether or not the patients had received adjuvant chemotherapy.

Objectives. Patients with rheumatoid arthritis (RA) and clinicians have different views about benefits from treatments. More knowledge is needed about how patients assess outcomes in order to update current measurements. Methods. Focus group interviews were performed at four Swedish rheumatology clinics. A total of 25 patients with RA were included, representing a wide range of ages and disease duration. Predetermined topics relating to important outcomes from and satisfaction/dissatisfaction with RA treatments were discussed. Results. The participants' initial outcome assessments included physical and psychosocial items, which comprised overall treatment goals such as impairment in social roles, fatigue, daily activities and self-confidence. The identified themes were 'Normal life', 'Physical capacity', 'Independence' and 'Well-being'. Satisfaction with treatment was associated with the quality of communication between staff and the patient. The participants assumed this as a prerequisite for a treatment to work. Patients wanted to be accepted as experts on their own bodies, and expected all clinicians to be experts on RA. This made it possible for patients to 'take charge' of their life situation. Good resources for and access to rheumatology care were desired. Conclusions. Suggesting a holistic approach to rheumatology care, the study results indicate that the illness and outcomes have to be evaluated within an individual RA patient's total life situation, described in the identified themes: 'Normal life', 'Physical capacity', 'Independence' and 'Well-being'. Development and validation of measurements covering these issues is suggested. More research is needed about communication and how patients experience their roles in the rheumatology clinic.

Both environmental and genetic factors are involved in the development of PD and biotransformation of exogenous and endogenous compounds and may play a role in inter-individual susceptibility. Therefore, we investigated the presence of null genotypes of GSTM1, GSTT1, and two polymorphisms of mEPHX in subjects with Parkinson's disease and in a reference population. The study included 35 male PD patients and a male control group including 283 subjects. Homozygosity of the histidine (H) 113 isoform of mEPHX was significantly increased in PD patients (odds ratio = 3.8 CI 95% 1.2–11.8) and analysis of allele frequencies displayed an increased frequency of the H-allele among PD patients (odds ratio = 1.9 CI 95% 1.1–3.3). However, a significantly elevated median age for the onset of PD was found among GSTM1 gene carriers (median age = 68 years) compared to PD patients being GSTM1 null genotypes (median age = 57 years). Our observations suggest that (H) 113 isoform of mEPHX, which has been suggested as a low activity isoform, is overrepresented in PD patients and that inherited carriers of the GSTM1 gene postpone the onset of PD. These detoxification pathways may represent important protective mechanisms against reactive intermediates modifying the susceptibility and onset of PD.

Exposure to organic solvents is still common in industrial and other work environments, and increases the risk of chronic toxic encephalopathy (CTE). Genetic variation in metabolic enzymes for solvents and other xenobiotics may modify the risk of developing toxic effects. Therefore, we investigated the presence of null genotypes for glutathione S-transferases M1 and T1 (GSTM1, GSTT1) and two genetic polymorphisms of microsomal epoxide hydrolase (mEPHX) in relation to the risk for chronic toxic encephalopathy (CTE) when exposed to solvents and smoking. We genotyped 115 patients who were classified into three categories: CTE (n = 56), incipient CTE (n = 27) and non-CTE (n = 32) patients. DNA was isolated from leucocytes and the GSTM 1 and GSTT1 null genotypes were determined by multiplex-polymerase chain reaction. The two polymorphisms of mEPHX were analysed by PCR-RFLP (restriction fragment length polymorphism) based assays. All analyses were performed blindly with regard to both exposure and disease status. An increased binomial regression risk ratio = 2.5, 95% confidence interval (CI) 1.5-4.2, of the GSTM1 null genotype for CTE was found in smokers and for the GSTT1 null genotype (binomial regression risk ratio 1.5, 95% CI 1.0-2.0). In nonsmokers, the GSTM1 null genotype did not confer any risk for CTE. None of the studied mEPHX polymorphisms were associated with an increased risk for CTE. We suggest that the GSTM1 null genotype in smokers is a possible risk for solvent-induced CTE.

ICSI is a highly efficient treatment of male factor infertility and therefore increasingly used to treat infertile men successfully. However, when used to treat patients with a genetic cause for their infertility, there may be an increased risk for the offspring. Chromosome aberrations, Y chromosome microdeletions and CFTR (cystic fibrosis transmembrane conductance regulator) mutations alone may explain up to 25% of azoospermia and severe oligozoospermia. These genetic defects could be identified before treatment, in which case informed decisions could be made by the couple to be treated concerning the treatment, prenatal testing or preimplantation genetic diagnosis. Therefore, we propose that men with very low sperm counts (<5 × 106/ml) considering ICSI should always be informed of the possibility of genetic testing. The information should include a precise statement of the implications of the results for the patient, his family and his offspring, and reassurance that a decision to test or not to test, or the subsequent test results will not be used as a reason for withholding treatment. Testing should always remain voluntary, and the couples themselves should decide whether or not they choose to be tested. If an abnormality is identified, patients should be referred to specialist genetic counselling.

The aims of the thesis were to develop a measure of fear during labor and to investigate women's experiences of fear and pain during labor and delivery as well as their levels of stress hormones. We also wanted to explore the associations between fear, pain, stress hormones and the duration of labor. Finally, we aimed to examine the relationships between pre-and postpartum fear, and fear and pain during labor.

The measurement of fear was developed in two substudies. First we composed a list of 60 fear-related items and their contrasts and tested it in a group of 92 women in labor. After psychometrical analyses, 10 items were selected for the final scale. The scale was then tested in another group of 57 women in labor. Via semi-structured interviews the content of the items was documented and analyzed.

Fifty-five nulliparous women participated in the investigation of women's experiences of fear, pain, levels of stress hormones and duration of labor. During gestation weeks 37-39, we measured levels of fear of childbirth, urinary catecholamines and salivary cortisol. During labor, hourly measurements were performed of fear, pain and levels of stress hormones. Finally, at two hours, two days and five weeks postpartum, fear of childbirth and stress hormones were measured.

The questionnaire that measures fear during labor was called the Delivery Fear Scale (DFS). The DFS has an alpha coefficient of .8 and has good psychometric qualities in both nulliparous and parous women. It takes women in labor between 30 and 90 seconds to listen to and answer all the statements. We found that nulliparous women had higher fear during phase 1 of labor (cervix dilatation 3-Scm) than parous women. Fear during phase 1 of labor predicted the total amount of pain relief received during labor, but not the duration of remaining part of labor, nor the occurrence of instrumental vaginal delivery or emergency cesarean section.

The results from the subsequently studies showed that there was an increase of the levels in stress hormones from pregnancy to labor. Epinephrine and cortisol increased more than 500% and norepinephrine approximately 50%. In women without EDA fear and cortisol increased throughout labor. In women with EDA cortisol did not increase, fear, pain and catecholamine levels first decreased after the administration of EDA but at the end of labor fear and pain increased. In phase 1, fear, but not pain, was more intensive in women who later subsequently received EDA than in those who did not. Fear and pain correlated positively during labor. A high level of epinephrine was associated with a shorter duration of phase 1 of labor. Postpartum fear of childbirth was higher in women who had received EDA during labor than in those who had not. Pre- and postpartum fear of childbirth correlated positively with fear but not with pain during phase 1 of labor.

In conclusion, DFS is a new measure of fear during labor with good psychometric qualities. Childbirth is a stressful event associated with exceptionally high levels of stress hormones. In this study women's experiences of fear and pain were associated throughout labor. The administration of EDA heavily influenced the course of fear, pain and stress hormones. Women who later received EDA had higher scores of fear but not of pain early during labor than those who did not receive EDA. Late pregnant women who fear childbirth are prone to have a fearful delivery, as reported during the actual labor and postpartwn.

Aims. To investigate the course of fear, pain and stress hormones during labor, and the associations between fear, pain, stress hormones and duration of labor in nulliparous women with and without epidural analgesia (EDA).

Method.  One day during gestation weeks 37–39, urinary and salivary samples were collected to measure catecholamines and cortisol. Hourly during labor, the participants answered the Delivery Fear Scale and a pain intensity scale, and urinary and salivary samples were collected to measure stress hormones.

Results. The course of fear, pain and stress hormones differed throughout labor in women with and without EDA. Pain and cortisol increased throughout labor in women without EDA. Women who received EDA had more fear, but not more pain, before the administration of the EDA than women who did not receive EDA. Pain, fear and catecholamines decreased when women received EDA, but fear and pain increased again later in labor. Fear and pain correlated, as well as levels of fear in the different phases of labor. During phase one of labor epinephrine and duration of the phase were negatively correlated.

Conclusion.  The course of fear, pain and concentrations of stress hormones differed, highly influenced by the administration of EDA. Fear and pain correlated more pronounced than stress hormones and fear, pain and duration of labor.

Background. Only scanty research exists about the relationship between women's expectations during pregnancy and their experiences as reported during the actual process of labor and afterwards. The aims of the present study were: 1. to investigate the associations between fear of childbirth during pregnancy and postpartum and fear and pain during early active labor (phase 1: cervix dilatation 3–5 cm), and 2. to explore possible differences regarding fear of childbirth during pregnancy and postpartum between women who did or did not receive epidural analgesia during labor.

Methods. Fear of childbirth was measured in 47 nulliparous women during gestation weeks 37–39 by means of the Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ version A). During early active labor we measured women's fear (Delivery Fear Scale) and their experiences of pain (a pain intensity scale). Finally, fear after childbirth (W-DEQ version B) was measured two hours, two days, and five weeks after delivery.

Results. A positive correlation appeared between fear of childbirth during pregnancy, postpartum, and early active labor. There were no differences in fear of childbirth during late pregnancy between women who received epidural analgesia and those who did not. Postpartum fear was higher in the women who had received epidural analgesia.

Conclusions. Pregnant women who fear childbirth are prone to report fear during the actual labor and postpartum. The administration of epidural analgesia is not a sufficient response to women's fear during the process of labor.

One way to study the stressfulness of childbirth is to examine the output of stress hormones. In this study, urinary catecholamines and salivary cortisol from 50 primiparous women were collected for 1 day during gestational weeks 37 to 39, hourly during labor and delivery, and 2 hr and 2 days postpartum. All three stress hormones increased statistically significantly from pregnancy to labor. The increase in adrenaline and cortisol was more than 500%, and the increase in noradrenaline was about 50%. After labor, the output decreased but not statistically significantly below the levels during late pregnancy. Hormone levels during late pregnancy, during labor and delivery, and during the period postpartum mostly did not correlate systematically. However, noradrenaline and adrenaline, as well as adrenaline and cortisol, were positively correlated during labor. After administration of epidural analgesia, there was a moderate but significant decrease in noradrenaline and adrenaline, whereas cortisol did not change. In conclusion, the results of this study support the assumption that childbirth is a very stressful event and that the stress responses vary considerably among women. The substantial increase of adrenaline and cortisol compared with noradrenaline indicates that mental stress is more dominant than physical stress during labor.

The aims of the present study were: (a) to examine whether it was possible to measure women’s cognitive appraisals hourly during the whole process of labor and delivery, and (b) to explore how the appraisals varied during labor. Measurements from 12 nulliparous women are presented. The findings indicate that it is possible to study psychological appraisals directly, in detail and continuously during the process of labor and delivery. The women’s cognitive appraisals varied throughout labor both per individual woman and between the participating women.

Background. The aims of the present study were to compare primiparous and multiparous women’s experiences of fear of delivery during an early stage of active labor (cervix dilatation 3–5 centimeters) and to study whether fear of delivery, measured during the early stage of active labor, was a predictor of the amount of pain relief received during the remaining part of labor (cervix dilatation 5 cm – partus), of the duration of the remaining part of labor, and of the occurrence of instrumental vaginal delivery and emergency cesarean section.

Method. Thirty-five primiparous and 39 multiparous women answered the Delivery Fear Scale (DFS) once during the early stage of labor and before they had received any pain relief.

Results. Primiparous women reported higher levels of fear than multiparous women did. Fear during the first phase of labor predicted only the total amount of pain relief received during labor.

Conclusion. The clinical implications of the study are that the delivery staff should consider women’s fear during labor and pay attention especially to primiparous women’s increased risk of higher levels of fear during an early stage of active labor, as compared with multiparous women’s. The challenge for staff of a delivery ward is to support the woman in labor in a way that decreases fear, which in turn might reduce the woman’s need of pain relief.

Aims: The aims of the present study were 1) to investigate the associations between fear of childbirth during pregnancy and postpartum and fear and pain during labor (phase 1: cervix dilatation 3-5 cm), and 2) to explore possible differences regarding fear of childbirth during pregnancy and postpartum between women who did or did not receive epidural analgesia (EDA) during labor.

Method. During gestation weeks 37-39, in 47 nulliparous women fear of childbirth was measured by means of the Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ) version A. Early during labor (labor phase I = cervix dilatation 3-5cm) the women's fear (Delivery Fear Scale) and their experiences of pain (a pain intensity scale) were measured hourly. Finally, fear after childbirth (W-DEQ version B) was measured two hours, two days, and five weeks after delivery.

Results. Fear of childbirth during pregnancy and in the three postpartum measures was positively related to fear during labor, phase I. Pain during phase 1 of labor was neither associated with fear of childbirth measured during late pregnancy, nor with postpartum fear. There were no differences in fear of childbirth during late pregnancy between those women who received EDA and those who did not. Postpartum fear was higher in those women who had received EDA.

Conclusion. Late pregnant women who fear childbirth are prone to have a fearful delivery, as reported during the actual labor and postpartum.

Osteoporosis is a major cause of morbidity worldwide. A number of risk factors, such as age and gender, are well established. High cadmium exposure causes renal damage and in severe cases also causes osteoporosis and osteomalacia, We have examined whether long-term Pow-level cadmium exposure increases the risk of osteoporosis. Bone mineral density (BMD) in the forearm was measured in 520 men and 544 women, aged 16-81 years, environmentally or occupationally exposed to cadmium, using dual-energy X-ray absorptiometry (DXA) technique. Cadmium in urine was used as the dose estimate and protein HC was used: as a marker of renal tubular damage. There was a clear dose-response relation between cadmium dose and the prevalence of tubular proteinuria. Inverse relations were found between cadmium dose, tubular proteinuria, and BMD, particularly apparent in persons over 60 years of age, There was a dose-response relation between cadmium dose and osteoporosis. The odds ratios (ORs) for men were 2.2 (95% CI, 1.0-4.8) in the dose group 0.5-3 nmol Cd/mmol creatinine and 5.3 (2.0-14) in the highest dose category (greater than or equal to 3 nmol/mmol creatinine) compared with the lowest dose group (<0.5 nmol Cd/mmol creatinine). For women, the OR was 1.8 (0.65-5.3) in the dose group 0.53 nmol Cd/mmol creatinine. We conclude that exposure to low levels of cadmium is associated with an increased risk of osteoporosis.

Background: Leukocyte scintigraphy is a noninvasive investigation to assess inflammation. We evaluated the utility of labeled leukocytes to detect small bowel inflammation and disease complications in Crohn's disease and compared it to whole small bowel enteroscopy and laparotomy findings. Methods: Scintigraphy with technetium-99m exametazime-labeled leukocytes was prospectively performed in 48 patients with Crohn's disease a few days before laparotomy, 41 also had an intraoperative small bowel enteroscopy. The same procedures were performed in 8 control patients. Independent grading of scans was compared with the results of enteroscopy and with surgical, histopathologic, and clinical data. Results: In the 8 control patients leukocyte scan, endoscopy, and histopathology were all negative for the small bowel. In patients with Crohn's disease and small bowel inflammation seen at enteroscopy and/or laparotomy (n = 39) the scan was positive in 33. In 8 patients without macroscopic small bowel inflammation, the scan was positive for the small bowel in 3 patients, at histology, 2 of 3 had inflammation. When combining results for patients and controls, the sensitivity of leukocyte scan for macroscopically evident small bowel inflammation was 0.85, specificity 0.81, accuracy 0.84, positive predictive value 0.92, and negative predictive value 0.68. Scintigraphy detected inflammatory lesions not known before laparotomy in 16 of 47 (34%) Crohn's disease patients and showed uptake in 25 of 35 (71 %) bowel strictures. It was diagnostic regarding 4 of 8 abscesses and 9 of 15 fistulas. In 6 patients (13%) lesions first demonstrated by leukocyte scintigraphy were treated during the surgery performed. Conclusions: Leukocyte scintigraphy reliably detects small bowel inflammation in Crohn's disease. It gives additional information on the presence of inflammatory lesions in a fraction of patients planned for surgery. Copyright © 2006 Crohn's & Colitis Foundation of America, Inc.

We examined the response to hepatitis B vaccination in dialysis patients, and evaluated our vaccination program to hepatitis B virus. No new cases of hepatitis B occurred during the study period, i.e. from 1980 and onwards. Sera were analyzed for anti-HBs in 25 dialysis patients vaccinated at least three times against hepatitis B and 53 health care staff vaccinated three times. The IgG subclass distribution of antibodies to hepatitis B surface antigen (anti-HBs) was determined in 11 dialysis patients and in 45 healthy controls. The antibody response to pneumococci was determined in 29 vaccinated patients.

Results: Ten of 25 (40%) of the dialysis patients had anti-HBs when both tests after the third and/or fourth injections were considered. In four patients a fourth injection was cancelled due to transplantation or bad health, while such data were lacking in 8 cases. In staff 49/53 (93%) of the persons responded with anti-HBs production. In anti-HBs positive patients and controls a significant difference in the response of healthy adults was observed in anti-HBs IgG 1 (p<0.001) vs all other IgG subclasses. Dialysis patients had low levels, or negative findings, in all cases, with lgGI as the highest proportion found (3/11 patients). An antibody response to pneumococcal vaccination was registred in 25 out of 29 dialysis patients (in all 86 %).Dialysis patients respond poorly to hepatitis B vaccine. An anti-HBs subclass response mainly restricted to IgG I was observed in healthy adults, while dialysis patients had low or negative test results affecting all subclasses.

The findings suggest a general deficit in the ability to produce anti-HBs rather than a deficit in the production of a specific subclass of this antibody. Moreover, RBV-vaccination schedules in renal transplant recipients should be started early, as some patients otherwise, due to transplantation or bad health, may not receive a fourth injection.

The antibody response to pneumococcal vaccination indicates that the antigen involved is important in vaccination responses in dialysis patients.

We studied history, renal histopathology and microbiology of an epidemic of acute glomerulonephritis associated with throat infections and uncommon culture results in four neighbour families. A 40-year-old man (index patient) was referred to a university hospital for dialysis and kidney biopsy due to a suspected acute glomerulonephritis. An acute tonsillitis had preceded the condition. Penicillin treatment had been started four days before the discovery of renal failure. Throat swabs were positive for β-hemolytic streptococci, group C (GCS). GCS were also found in throat cultures from his wife and two of their children. The bacteria were typed as Streptococcus constellatus. A third child had S. constellatus expressing Lancefield antigen group G. A neighbour and two of his children fell ill the following week with renal involvement. Throat swabs from both these children were positive for S. constellatus. His third child had erythema multiforme and S. constellatus in the throat while a fourth child had β-hemolytic streptococci group A, Streptococcus pyogenes. Kidney biopsies on the index patient and his neighbour showed an acute diffuse prolipherative glomerulonephritis compatible with acute post-streptococcal nephritis and microbiological analysis of renal tissue revealed in both cases S. pyogenes and S. constellatus. The families had had much contact and had consumed unpasteurized milk from our index patient's farm. In four of seven persons in two additional neighbouring families S. constellatus was found in throat swabs during the same month while two persons carried Streptococcus anginosus expressing the Lancefield C antigen. In conclusion spread of S. constellatus coincided with the occurrence of four cases of acute glomerulonephritis. The two biopsied patients had both S. pyogenes and S. constellatus present in renal tissue. The epidemic either suggested that the outbreak of glomerulonephritis was due to S. pyogenes but coincided with the transmission and colonization of S. constellatus or that the S. constellatus strains were highly pathogenic or nephritogenic and that this organism can be transmitted in such cases.

Hepatitis B is a well known problem in dialysis units. We therefore examined the historical frequency of hepatitis B carriers in our unit, our vaccination program to hepatitis B virus (HBV), the response to hepatitis B vaccine, the IgG subclass response of anti-HBs and the response and IgG subclass response to pneumococcal vaccination (another vaccine) in dialysis patients. From 1970 and onwards 23 HBV carriers were found, but no new cases of hepatitis B occurred during the study period, i.e. from 1980 and onwards.Only one of the carriers was alive by the end of 2001. In four patients liver disease(in one of them liver cirrhosis) may have been a concomitant cause of death. The antibody response to hepatitis B vaccine was significantly lower in patients than in staff. In four patients a fourth injection was cancelled due to transplantation and bad health, while such data were lacking in 8 cases. In anti-HBs positive patients and controls a significant difference in the response of healthy adults was observed in anti-HBs IgG1 (p<0.001) vs all other IgG subclasses. Dialysis patients had low levels, or negative findings, in all cases, with IgG1 as the highest proportion found (3/11 patients). An antibody response to pneumococcal vaccination was registered in 25 out of 29 dialysis patients (in all 86 %). The IgG-subclass vaccination response to pneumococci in 28 dialysis patients was mainly IgG2 and IgG1 but also occurred in IgG3 and IgG4. Prevaccination antibody levels of the controls were higher in IgG1 and IgG2 (p< 0.01) (n=21) than in dialysis patients (n=28). Hepatitis B is nowadays a rare, but still dangerous disease in nephrology units. Dialysis patients have a reduced response to hepatitis B vaccine and vaccination schedules should be started early as some patients otherwise may not receive a fourth injection. The adequate antibody response to pneumococcal vaccination mainly due to IgG2 and IgG1 antibodies indicates that the antigen involved is important in vaccination responses in dialysis patients.

In the aortic intima amyloid deposits are often associated with atherosclerotic plaques. In a recent study of one patient with aortic intimal amyloid the major fibril protein was an N-terminal fragment of apolipoprotein A1 (apoA1) consisting of 69 amino acid residues. In the present study, we have screened the apoA1 gene for mutations in autopsy cases with aortic intimal amyloid immunohistochemically positive for apoA1, using single stranded conformational polymorphism (SSCP) analysis and DNA sequencing. All cases except one had a normal apoA1 gene sequence. One case of exceptionally severe atherosclerosis combined with extensive intimal amyloid deposits showed an apoA1 deletion corresponding to Lys 107. Thus, wild type apoA1 is amyloidogenic but our findings suggest that the expression of a mutant apoA1-form may be associated with enhanced amyloidogenicity.

Yersinia pseudotuberculosis evades the immediate immune defense of a host organism by inhibiting bactericidal functions of phagocytes, including phagocytosis, cytokine release, and the oxidative burst. Consequently, this pathogen can survive and multiply in lymphatic tissues. An ensemble of proteins called Yops are involved in the virulence of Y. pseudotuberculosis. Through a polarized mechanism, certain Yops are translocated directly into the host cell, where they are assumed to exert their effects. The present studies were performed to gain further knowledge about the role of the tyrosine phosphatase YopH in Yersinia virulence, especially in regard to effects on the immediate functions and signals of phagocytes.

Y. pseudotuberculosis was found to resist phagocytic uptake by a mechanism involving translocation of bacterially synthesized YopH into the target cell. The antiphagocytic mechanism had an impact on ingestion of both non-opsonized and IgO-opsonized bacteria. Phagocytosis of a YopH-negative strain was accompanied by induction of tyrosinephosphorylated cellular proteins (among them paxillin), and this involved binding of the bacterial surface protein invasin to ß1 integrins of the eukaryotic cell, which also initiated an immediate Ca²⁺ signal in the target cell. The phosphotyrosine proteins Cas and FYB were recruited to the focal complex area during phagocytosis of the YopH-negative strain. Furthermore, we found that a phosphatase-inactive YopH eo-localized with focal adhesion to the periphery of a host cell. In phagocytes infected with wild-type bacteria, phosphatase-active YopH dephosphorylated Cas and FYB, which caused disruption of focal complex structures, and inhibition of the Ca2+ signal. The phosphorylation events as well as the Ca²⁺ signal were rapid responses to bacterial attachment, suggesting that the action of YopH is instantaneous.

Genetic studies revealed that the YopH protein contain an inherent sequence important for anchoring at focal complex structures. Specifically, deletion of the amino acids 223-226 disabled YopH to localize to the focal complexes and to inhibit phagocytosis and Ca²⁺-signaling. This indicates that Y opH must bind to a specific site in focal complexes to focus its activity on the appropriate substrates (i.e. Cas and FYB). Our results show that targeting such complexes is important for Y. pseudotuberculosis, not only as a means of avoiding ingestion by phagocytes, but also for its virulence in mice.

Pathogenic species of the genus Yersinia evade the bactericidal functions of phagocytes. This evasion is mediated through their virulence effectors, Yops, which act within target cells. In this study we investigated the effect of Yersinia pseudotuberculosis on Ca ²⁺ signaling in polymorphonuclear neutrophils. The intracellular free calcium concentration in single adherent human neutrophils was monitored during bacterial infection and, in parallel, the encounter between the bacteria and cells was observed. When a plasmid-cured strain was used for infection, adherence of a single bacterium to the cellular surface induced a β ₁ integrin-dependent transient increase in the intracellular concentration of free calcium. This was, however, not seen with Yop-expressing wild-type bacteria, which adhered to the cell surface without generating any Ca ²⁺ signal. Importantly, the overall Ca ²⁺ homeostasis was not affected by the wild-type strain; the Ca ²⁺ signal mediated by the G-protein-coupled formyl-methionyl-leucyl- phenylalanine receptor was still functioning. Hence, the blocking effect was restricted to certain receptors and their signaling pathways. The use of different Yop mutant strains revealed that the protein tyrosine phosphatase YopH was responsible for the inhibition. This virulence determinant has previously been implicated in very rapid Yersinia-mediated effects on target cells as the key effector in the blockage of phagocytic uptake. The present finding, that Y. pseudotuberculosis, via YopH, specifically inhibits a self- induced immediate-early Ca ²⁺ signal in neutrophils, offers more-detailed information concerning the effectiveness of this virulence effector and implies an effect on Ca ²⁺-dependent, downstream signals.

Background: The treatment of Crohn's disease has changed owing to the recognition of its chronicity. Medical maintenance treatment and limited resections have evolved as major concepts of management, regarded as complementary, and both aim at reducing the symptoms.

Methods: We investigated the symptomatic load in Crohn's disease as reflected in a cross-sectional study of the symptom index, physicians' assessment, and the patients' perception of health. A cohort of 212 patients from the primary catchment area and 125 referred patients were studied.

Results: Of catchment area patients, 83% were receiving medication, and the annual rate of abdominal surgery was 5.7%. Corresponding figures for the referred patients were 82% and 10.3%. According to the symptom index, 87% of catchment area patients were in remission or had only mild symptoms; according to the physicians' assessment, 90% were. The patients' median perception of health was 90% of perfect health according to the visual analogue scale. The figures were similar for referred patients, except that referrals were considered more diseased by the physician.

Conclusion: The great majority of patients with Crohn's disease are able to live in remission or experience only mild symptoms.

Background: This study describes how surgery for Crohn colitis developed between 1970 and 1997, towards the end of which period limited resection and medical maintenance treatment was introduced.

Methods: A cohort of 211 patients with Crohn colitis (115 population-based), of which 84 had a primary colonic resection (42 population-based), was investigated regarding indication for surgery, the time from diagnosis to operation, type of primary colonic resection, risk for permanent stoma and medication over four 7-year periods.

Results: Comparison of the periods 1970-90 and 1991-97 revealed that active disease as an indication for surgery decreased from 64% to 25% ( P < 0.01) while stricture as an indication increased from 9% to 50% ( P < 0.001). Median time from diagnosis to operation increased from 3.5 to 11.5 years ( P < 0.01). Proctocolectomy or colectomy fell from 68.8% to 10% of the primary resections, whereas segmental resection increased from 31.2% to 90%. At the end of the first 7-year period, 26% had medical maintenance treatment, steroids or azathioprine taken by 7%. Corresponding figures for the last period were 70% and 49%. Patients diagnosed during the last two time-periods had less risk for surgery ( P = 0.017), permanent stoma ( P < 0.01) and total colectomy ( P < 0.01). Findings were similar in the population-based cohort.

Conclusions: Current management of Crohn colitis implies a longer period between diagnosis and surgery, a reduced risk for surgery and permanent stoma, and the replacement of total colectomy by segmental resection.

Background & Aims: Appendectomy is associated with a low risk of subsequent ulcerative colitis. This study analyzes the risk of Crohn's disease after appendectomy. Methods: We followed-up 212,218 patients with appendectomy before age 50 years and a cohort of matched controls, identified from the Swedish Inpatient Register and the nationwide Census, for any subsequent diagnosis of Crohn's disease. Results: An increased risk of Crohn's disease was found for more than 20 years after appendectomy, with incidence rate ratio 2.11 (95% confidence interval [CI], 1.21-3.79) after perforated appendicitis, 1.85 (95% CI, 1.10-3.18) after nonspecific abdominal pain, 2.15 (95% CI, 1.25-3.80) after mesenteric lymphadenitis, 2.52 (95% CI, 1.43-4.63) after other diagnoses. After nonperforated appendicitis, there was an increased risk among women but not among men (incidence rate ratio 1.37, 95% CI, 1.03-1.85, respectively, 0.89, 95% CI, 0.64-1.24). Patients operated on before age 10 years had a low risk (incidence rate ratio 0.48, 95% CI, 0.23-0.97). Crohn's disease patients with a history of perforated appendicitis had a worse prognosis. Conclusions: Appendectomy is associated with an increased risk of Crohn's disease that is dependent on the patient's sex, age, and the diagnosis at operation. The pattern of associations suggests a biologic cause.

Background. The clinical effects of percutaneous transluminal renal artery angioplasty (PTRA) in patients with renal vascular stenosis and hypertension is controversial. Methods. We consecutively recruited all 23 patients referred for evaluation of renovascular hypertension that eventually underwent unilateral PTRA, to be investigated with captopril MAG3 renography (CR), both before and after the endovascular procedure. Data were evaluated on an intention-to-treat basis. Results. We found that the relative MAG3 clearance of the stenotic kidney increased (from 29.9 ± 14% to 35.1 ± 14%, p=0.01) and that the creatinine levels fell following the intervention (from 110 ± 19 to 99 ± 17 μmol/l, p=0.0003). Blood pressure levels were also lowered (from 173 ± 32/93 ± 17 to 158 ± 31/86 ± 15 mmHg, p<0.006) while the mean number of anti-hypertensive drugs was unchanged following PTRA (2.9 ± 1.4 before and 2.8 ± 1.3 drugs after the intervention, respectively, p-0.6). Conclusion. This prospective trial showed statistically significant improvements of individual kidney function as measured by CR and blood pressure in subjects with suspected renovascular hypertension treated with PTRA. Although the endovascular procedure was found to be safe, the magniture of the absolute improvements was rather modest. © 2005 Taylor & Francis.

Background. This study is part of a community-based intervention programme dealing with the prevention of osteoporosis. The study aims were to estimate the calcium intake from dairy products and calcium supplements within a general population, and thereafter to study associations between calcium intake, relevant lifestyle factors, and forearm bone mineral density.

Methods. A randomised sample of 15 % of the inhabitants aged 20 - 79 years ( = 1510) from two Swedish municipalities answered a questionnaire, and a selected sub-sample (n=448) had their forearm bone mineral density measured.

Results. The mean consumption of calcium from dairy products was 878 mg/day. Men consumed more than women, and calcium intake decreased with increasing age. Twelve percent of the youngest age group in the study population and 31 % of the oldest age group did not meet the recommended daily intake. Associations were found between calcium intake and both residence and physical activity. There was a tendency towards an association between calcium intake and forearm bone mineral density. No other associations with lifestyle factors were observed.

Conclusion. Calcium intake is in general well attained in an adult Swedish population, although the intake range is wide (55 to 3213 mg/day from dairy products). Women aged 50-59 years and older people are at increased risk of not meeting the recommended daily intake.

Background: Atopic diseases have increased over the last decades in Westem countries. In order to understand the process underlying primary sensitisation to allergens we need to augment our knowledge of the maturation of T lymphocytes and monocytes in small children. The main aim was to prospectively study the development of T lymphocytes and monocytes in children who subsequently developed atopic disease.

Material and Methods: Children (n=170) with or without an atopic family history were followed from birth to 18 months of age, and a subgroup of 38 children were followed-up also at the age of seven. The cumulative history of atopic disease was recorded. A skin prick test (SPT) was performed at 18 months and at 7 years. T-cell surface markers (CD2, 3, 4, 8, 28) were studied in all children with flow cytometry at birth, and at 18 months. These markers were also studied at 3, 6, and 12 months in a subgroup of 78 children with either strong or no atopic family history. At 18 months 54 children, 29 non-atopic and 25 atopic, were included in a functional T-cell study. Phytohaemagglutinin (PHA) or antiCD3 induced proliferation in peripheral blood mononuclear cells (PBMC) was studied by analysing 3H-thymidine incorporation. Anti-CD3 induced cytokine production (IL-4, IL-5, IL-6, IL-10, IL-13 and IFN-γ) was analysed by enzyme-linked innnuno sorbent assay (ELISA). At the age of seven 38/54 children were followed-up and the responsiveness to IL-12 was studied after stimulation with IL-2, IL-12 or both. The expression of iL-12Rß2 mRNA PBMCs was measured with real time PCR, as well as the cytokines IL-5, IL-10 and IFN-γ (ELISA). The monocyte surface marker CD14 was studied with flow cytometty in a subgroup of 76 children at bitth, 3, 6, 12 and 18 months of age, as well as soluble CD14 in serum by ELISA, and total immunoglobulin E (IgE) by UniCAP®. Soluble CDI4 (sCD14) and total lgE were also analysed in the subgroup of 38 children at seven years of age.

Results: At 18 months 118/170 children were non-atopic and 31/170 had developed atopic disease. CD4 fluorescence intensity (Fl) on T-helper-(CD3+CD4+) cells was lower at birth and at 3 months in children with a cumulative history of atopy at 18 months than in nonatopics. Atopy was associated with a low proportion of CD2+ lymphocytes at 18 months. At this age children with a cumulative atopy and a positive SPT had lower CD2 FI, as well as lower CD3 Fl on pan T cells (CD3+CD45+CD14- cells) and higher CD28 Fl on CD2+CD8+CD28+ cells. Atopic disease at 18 months was associated with high levels of anti-CD3 induced IL-5 secretion and SPT-negative children with atopic disease produced higher levels of IL-l 0, than SPT -positive children. The IL-4/ IL-l 0 and IL-4/IFN-y ratios were higher in children with elevated total IgE levels. At age seven children with atopic aitway symptoms up-regulated the expression of IL-2 induced IL-12RP2 mRNA less than non-atopic children. This was accompanied by a low IL-2 and IL-12 induced IFN-y scretion. Fmther sCD 14 was lower at seven years in children with a cumulative histmy ofatopic disease, than in non-atopic children. This patte1n was also observed at 3 and 18 months in SPT-positive children with a cumulative histmy of atopy at 18 months compared to non-atopic SPT-negative children. In addition, children with a strong AFH had lower levels of sCD14 at 3, 12, and 18 months and at 7 years than children with no AFH.

Conclusions: The maturation of T cells and T-cell function differs between atopic and non-atopic children. IL-12 responsiveness is reduced in children with atopic ahway symptoms and high levels of total-IgE. Altogether this may contribute to a Th2 deviated immunity in atopic disease. Atopic children have reduced levels of sCD14. The low levels may be a consequence of the atopic disease/atopic family heredity and may also reflect a reduced capacity to respond to microbial signals in atopic individuals.

Background: There is little information available about the development of T–cell immunity in healthy and atopic children. We have studied prospectively the mean fluorescence intensity of the T–cell receptor complex–associated CD3, CD4 and CD8 in relation to atopic family history (AFH) and the development of atopic disease.

Methods: Children with a defined AFH (n = 172) were followed from birth to 18 months and the cumulative history of atopic disease was recorded. Blood samples were obtained at birth and at 18 months, and in a subgroup of 78 children also at 3, 6 and 12 months. Multicolour flow cytometry was used to analyse pan T–cells (CD3+CD45+CD14–), T–helper–(CD3+CD4+) and T–cytotoxic–(CD3+CD8+) cells.

Results: At 18 months, 31 children were atopic and 118 non–atopic. Children who developed atopic disease had a higher CD4 expression (mean fluorescence intensity, MFI) on CD4+CD3+ lymphocytes at birth and at 3 months, particularly as compared with non–atopic children without AFH. Furthermore, the CD3 expression on CD3+CD45+CD14– lymphocytes increased more slowly with age in children with double atopic heredity, as compared with children with no or only one atopic family member.

Conclusions: The higher expression of the CD4 receptor in early infancy in children who developed atopic disease compared with non–atopics suggests a delayed expression in T–helper cells. Children with a strong AFH had a slower increase in the expression of CD3, indicating a delayed T–cell maturation.

Aim: To investigate the characteristics of severe abuse of children and possible differences in comparison with less severe abuse. Method: Cases of abuse reported to the police within a single police district (n = 142) in Sweden were studied. The severe cases were compared to all the remaining cases. Results: Severe abuse constituted 14% of the total cases and was reported by agencies to a greater degree than minor cases. The suspected perpetrators were socially disadvantaged people in both groups. Half of the most serious cases led to conviction in the courts, compared to 8% in the reference group. The children who had been subjected to abuse were often already known to social services and reports of child abuse had frequently been made. Conclusion: In comparison between cases of severe and minor child abuse reported to the police, the results did not show any crucial differences except the pattern of reporting and a higher occurrence of prosecution/conviction in the severe cases. This finding places a responsibility on agencies outside of the justice system to consider all cases of reported abuse as serious warning signals and to make independent evaluations to identify risks and the possible need for child protection. © 2007 The Author(s).

Background: The prevalence of asthma and allergic diseases is significantly lower in post socialist Eastern Europe than in Western industrialized countries. The reason for this difference is largely unknown. Different types of childhood wheezing could be related to different risk factors. Objective: To compare the prevalence of respiratory symptoms, asthma and atopic diseases among Estonian and Swedish schoolchildren and to evaluate characteristics for wheezing in the two countries. Methods: In a prevalence study, population-based random samples of 10-11-year-old schoolchildren in Tallinn (n = 979), Estonia and in Link÷ping (n = 911) and ╓stersund (n = 1197), Sweden were studied by a parental questionnaire and skin prick tests (SPT). All 275 children with wheeze in the past 12 months and 710 randomly selected controls within the original cohorts were invited to a case-control study involving a parental questionnaire, examination for flexural dermatitis and bronchial challenge with hypertonic saline. The study adhered to the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II protocol. Results: The prevalence of current wheezing was similar (8-10%) in the three centres, while diagnosed asthma and atopic symptoms were more common in Sweden and cold-related respiratory symptoms were more prevalent in Estonia. Frequent wheezing was more common in Sweden than in Estonia (but significantly so only in ╓stersund). Wheezing children in Sweden had a high rate of positive SPT (49% in Link÷ping and 58% in ╓stersund) bronchial hyper-responsiveness (BHR) (48% in Link÷ping and ╓stersund) and anti-asthmatic treatment (63% in Link÷ping and 81% in ╓stersund). In Estonia, the proportion of wheezing children with positive SPT, BHR and anti-asthmatic treatment was only 26%, 13% and 17%, respectively. Domestic crowding was inversely related to wheezing in one of the study areas (╓stersund). The mean baseline forced expiratory volume in one second (FEV1) was higher in Estonia than in Sweden, both in wheezing and non-wheezing children. Conclusions: Our study suggested that although wheezing symptoms were equally common in Estonia and Sweden, they were less severe in Estonia. More frequent symptoms and a high rate of atopy, BHR and anti-asthmatic medication characterized wheezing children in Sweden. In contrast, BHR, atopy and medication were uncommon among wheezing children in Estonia.

Introduction: There is little information available on the effects of problem-based undergraduate curricula on doctors and their performances after graduation. Therefore, we conducted a questionnaire study of all graduates of the new medical programme at the Faculty of Health Sciences, Link÷ping University. Methods: All 446 medical students who had graduated from the new programme were asked to fill in a questionnaire about selected activities during their studies and their careers after graduation. They were also asked to evaluate the quality of their undergraduate education retrospectively. Statistical analysis was performed using descriptive, multivariate and bivariate approaches. Results: A total of 77% of the graduates responded. They showed a high degree of overall contentment with their undergraduate education and felt well prepared for professional life during their preregistration period and specialist education (mean = 4.0 on a 6-point Likert scale ranging from 0 to 5). They felt especially well prepared in terms of skills for communication with patients, collaboration with other health professionals and development of critical thinking/scientific attitudes. The students' age at the beginning of their studies correlated positively with their contentment as graduates, especially in terms of preparation for patient communication and collaboration with other health professionals. No differences between students originally admitted via a local admission procedure and those admitted via a national procedure were detected concerning retrospective evaluation of undergraduate medical education. Conclusion: Graduates of the new curriculum showed a high degree of satisfaction with their undergraduate education and its preparation of them for medical practice. Specifically, they were very content with the particular emphases of the new curriculum.

To evaluate the hormonal response to stress in healthy preterm infants, we measured concentrations of serum cortisol at baseline and after capillary heelstick. Eleven preterm infants, five girls and six boys, with gestational ages ranging from 30 to 34 weeks, were studied. We measured the serum cortisol concentration before and 30 min after capillary heelstick on days 1, 3 and 7 of life. On days 3 and 7, but not on day 1, the rise in cortisol was significant (p = 0.02 and 0.04, respectively). The reduced response on day 1 can probably be explained by the significantly higher baseline concentrations. We suggest that a test like this can be useful in evaluating the hormonal stress response in preterm as well as full-term infants.

Background: Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, and maybe also of leukaemia and multiple myeloma. The effect of tumour necrosis factor (TNF) antagonists on lymphoma risk and characteristics is unclear. Objective: To assess expected rates and relative risks of haematopoietic malignancies, especially those associated with TNF antagonists, in large population based cohorts of patients with RA. Methods: A population based cohort study was performed of patients with RA (one prevalent cohort (n = 53 067), one incident cohort (n = 3703), and one TNF antagonist treated cohort 1999 through 2003 (n = 4160)), who were linked with the Swedish Cancer Register. Additionally, the lymphoma specimens for the 12 lymphomas occurring in patients with RA exposed to TNF antagonists in Sweden 1999 through 2004 were reviewed. Results: Study of almost 500 observed haematopoietic malignancies showed that prevalent and incident patients with RA were at increased risk of lymphoma (SIR =1.9 and 2.0, respectively) and leukaemia (SIR = 2.1 and 2.2, respectively) but not of myeloma. Patients with RA treated with TNF antagonists had a tripled lymphoma risk (SIR = 2.9) compared with the general population. After adjustment for sex, age, and disease duration, the lymphoma risk after exposure to TNF antagonists was no higher than in the other RA cohorts. Lymphomas associated with TNF antagonists had characteristics similar to those of other RA lymphomas. Conclusion: Overall, patients with RA are at equally increased risks for lymphomas and leukaemias. Patients with RA treated with TNF antagonists did not have higher lymphoma risks than other patients with RA. Prolonged observation is needed to determine the long term effects of TNF antagonists on lymphoma risk.

Background: Existing studies of solid cancers in rheumatoid arthritis (RA) reflect cancer morbidity up until the early 1990s in prevalent cohorts admitted to hospital during the 1980s. Objective: To depict the cancer pattern of contemporary patients with RA, from updated risk data from prevalent and incident RA populations. To understand the risk of solid cancer after tumour necrosis factor (TNF) treatment by obtaining cancer data from cohorts treated in routine care rather than trials. Methods: A population based study of three RA cohorts (one prevalent, admitted to hospital 1990-2003 (n = 53 067), one incident, diagnosed 1995-2003 (n = 3703), and one treated with TNF antagonists 1999-2003 (n = 4160)), which were linked with Swedish nationwide cancer and census registers and followed up for cancer occurrence through 2003. Results: With 3379 observed cancers, the prevalent RA cohort was at marginally increased overall risk of solid cancer, with 20-50% increased risks for smoke related cancers and +70% increased risk for non-melanoma skin cancer, but decreased risk for breast (-20%) and colorectal cancer (-25%). With 138 cancers, the incident RA cohort displayed a similar cancer pattern apart from non-decreased risks for colorectal cancer. TNF antagonist treated patients displayed solid cancer (n = 67) risks largely similar to those of other patients with RA. Conclusion: The cancer pattern in patients treated with TNF antagonists mirrors those of other contemporary as well as historic RA cohorts. The consistent increase in smoking associated cancers in patients with RA emphasises the potential for smoking cessation as a cancer preventive measure in RA.

Objectives: The degree to which treatment with tumour necrosis factor (TNF) antagonists may be associated with increased risks for serious infections is unclear. An observational cohort study was performed using prospectively collected data from the Swedish Biologics Register (ARTIS) and other national Swedish registers. Methods: First, in the ARTIS, all 4167 rheumatoid arthritis (RA) patients starting TNF antagonist treatment between 1999 and 2003 were identified. Secondly, in the Swedish Inpatient Register, all individuals hospitalised for any reason and who also carried a diagnosis of RA, between 1964 and 2003 (n = 44 946 of whom 2692 also occurred in ARTIS), were identified. Thirdly, in the Swedish Inpatient Register, all hospitalisations listing an infection between 1999 and 2003 were identified. By cross-referencing these three data sets, RRs for hospitalisation with infection associated with TNF antagonist treatment were calculated within the cohort of 44 946 RA patients, using Cox regression taking sex, age, geography, co-morbidity and use of inpatient care into account. Results: Among the 4167 patients treated with TNF antagonists, 367 hospitalisations with infections occurred during 7776 person-years. Within the cohort of 44 496 RA patients, the RR for infection associated with TNF antagonists was 1.43 (95% Cl 1.18 to 1.73) during the first year of treatment, 1.15 (95% Cl 0.88 to 1.51) during the second year of treatment, and 0.82 (95% Cl 0.62 to 1.08) for subjects remaining on their first TNF antagonist treatment after 2 years. Conclusion: Treatment with TNF antagonists may be associated with a small to moderate increase in risk of hospitalisation with infection, which disappears with increasing treatment duration.

Objective. Because treatment with tumor necrosis factor (TNF) antagonists may increase the risk of tuberculosis (TB), and because knowledge of the risk of TB in rheumatoid arthritis (RA) not treated with biologics is scarce and of uncertain generalizability to low-risk populations, this study sought to determine the risk of TB among Swedish patients with RA. Methods. Using data from Swedish nationwide and population-based registers and data from an ongoing monitoring program of TNF antagonists, the relative risks of TB in patients with RA (versus the general population) and of TB associated with TNF antagonists (versus RA patients not treated with biologics) were determined by comparing the incidence of hospitalization for TB in 3 RA cohorts and 2 general population cohorts from 1999 to 2001. We also reviewed the characteristics of all reported cases of TB in RA patients treated with TNF antagonists in Sweden and calculated the incidence of TB per type of TNF antagonist between 1999 and 2004. Results. During 1999-2001, RA patients who were not treated with TNF antagonists were at increased risk of TB versus the general population (relative risk 2.0, 95% confidence interval [95% CI] 1.2-3.4). RA patients treated with TNF antagonists had a 4-fold increased risk of TB (relative risk 4.0, 95% CI 1.3-12) versus RA patients not treated with TNF antagonists. The reported TB cases during 1999-2004 in RA patients exposed to TNF antagonists (9 infliximab, 4 etanercept, 2 both) were predominantly pulmonary. TB occurred up to 3 years following the start of treatment. Conclusion. Irrespective of whether TNF antagonists are administered, Swedish patients with RA are at increased risk of TB. During 1999-2001, TNF antagonists were associated with an increased risk of TB, up to 4-fold in magnitude. This increased risk may persist over time during treatment and is related to both infliximab and etanercept. © 2005, American College of Rheumatology.

Objectives: To evaluate the effect of the Feldenkrais intervention, in fibromyalgia patients. Methods: Twenty fibromyalgia patients started Feldenkrais intervention done as one individual and two group sessions weekly for 15 weeks. Nineteen started a group-based pain education program followed by a pool program. Test and self-report questionnaires were administered at the start, at six month follow up, and at the end of intervention. Results: After the Feldenkrais intervention improvement in balance and trends to better lower extremity muscle function were shown, but the improvements were not maintained. Conclusions: No sustained benefit of the Feldenkrais intervention compared to a pool program was seen. Methodological problems are discussed. ⌐ 2001 by The Haworth Press, Inc. All rights reserved.