Case management at an outpatient unit for severe and enduring eating disorder patients at Stockholm Centre for Eating Disorders- a study protocol.

BACKGROUND: Patients with severe and enduring eating disorders (SEED) are seriously ill and have a low quality of life. Case management (CM), originally developed for adult patients with severe mental disabilities, has been shown to enhance social functioning and improve quality of life, while reducing the number and length of hospitalizations. In 2014, a special unit based on CM, for patients with SEED (the Eira unit) was started at Stockholm Centre for Eating Disorders, Sweden. METHOD/DESIGN: This study aims to investigate if CM can improve SEED patients' quality of life, and reduce their eating disorder symptoms as well as their health care consumption. Methods for data collection are a semi-structured diagnostic interview, self-report questionnaires, and a qualitative interview. The diagnostic interview and the self-report assessments will be done at start of treatment and at follow-ups after 1, 2, and 3years. The qualitative interview will be conducted 1 year after start of treatment. The study is approved by the ethical review board in Stockholm in compliance with the Helsinki Declaration. DISCUSSION: CM is a possible new contribution to the treatment methods for SEED. It does not aim at remission, but rather to accept life as it is, and to enhance quality of life in the presence of the ED. This study will investigate the potential benefits of this novel intervention in a special unit for SEED patients. TRIAL REGISTRATION: Clinicaltrials.gov Id: NCT02897622.

Sunlight is associated with decreased multiple sclerosis risk: no interaction with human leukocyte antigen-DRB1*15.

BACKGROUND: Both insufficient exposure to sunlight and vitamin D deficiency have been associated with an increased risk for multiple sclerosis (MS). An interaction between human leukocyte antigen HLA-DRB1*15 and vitamin D in MS was recently proposed. We investigated the association between previous exposure to ultraviolet radiation (UVR), vitamin D status at inclusion in the study, and MS risk including the interaction of these factors with HLA-DRB1*15. METHODS: A population-based case-control study involving 1013 incident cases of MS and 1194 controls was performed in Sweden during 2005-2010. Subjects were classified according to their UVR exposure habits, vitamin D status, and HLA genotypes. The associations between different sun exposure habits/vitamin D levels and MS were calculated as odds ratios (OR) with 95% confidence intervals (CI) using logistic regression. Potential interaction was evaluated by calculating the attributable proportion due to interaction. RESULTS: Subjects with low UVR exposure had a significantly increased risk of MS compared with those who reported the highest exposure (OR 2.2, 95% CI 1.5-3.3). Similarly, subjects who had 25-hydroxy-vitamin D levels less than 50 nM/l had an increased risk for MS (OR 1.4, 95% CI 1.2-1.7). The association between UVR exposure and MS risk persisted after adjustment for vitamin D status. There was no interaction with HLA-DRB1*15 carriage. CONCLUSIONS: UVR and vitamin D seem to affect MS risk in adults independently of HLA-DRB1*15 status. UVR exposure may also exert a protective effect against developing MS via other pathways than those involving vitamin D.

Serum cardiac troponin T in patients hospitalized with heart failure is associated with left ventricular hypertrophy and systolic dysfunction.

BACKGROUND: Cardiac troponin T (cTnT) is a highly sensitive and specific marker of acute myocardial infarction. Serum cTnT is also slightly elevated in patients with severe heart failure and is associated with left ventricular hypertrophy (LVH) in patients treated with haemodialysis. In this study serum cTnT concentrations and echocardiographic findings were investigated in heart failure patients without acute coronary syndrome. cTnT was also compared with other cardiac markers and plasma levels of brain natriuretic peptide (BNP). METHODS: Twenty-six patients hospitalized with heart failure were included in the study. Echocardiographic measurements and blood sampling were carried out 12-36 h after admission. Serum cTnT (3rd generation assay), cardiac troponin I (cTnI), creatine kinase MB (CKMB) and CK were measured. Plasma BNP was analysed using the Shionoria assay. LVH was defined as left ventricular mass index (LVMI) > 125 g/m for males and > 110 g/m for females. Left ventricular systolic function was estimated from the mitral annulus motion (AV-mean LV). RESULTS: Median cTnT was 0.012 (< 0.010-0.032) microg/L. Sixty-two percent of the patients (16 of 26) had elevated serum cTnT >or= 0.010 micro/L. cTnT was positively correlated with CKMB (rho = 0.40, p = 0.04) and BNP (rho = 0.43, p = 0.03), but not with cTnI and CK. A negative correlation was found between cTnT and AV-mean LV (rho = -0.58, p = 0.007), and there was a positive correlation between cTnT and LVMI (rho = 0.44, p = 0.03). No other analyte was correlated to LVMI. CONCLUSIONS: Serum cTnT but not cTnI was associated with left ventricular dysfunction and LVH in patients hospitalized with heart failure. This explains why cTnT tends to be slightly elevated in patients with heart failure without symptoms of acute myocardial ischaemia.

Elevated cardiac troponin T in predialysis patients is associated with inflammation and predicts mortality.

OBJECTIVES: Cardiac troponin T (cTnT) is a highly sensitive and specific marker of myocardial damage. It has been shown that elevated serum concentrations of cTnT in haemodialysis (HD) patients are associated with poor prognostic outcome. The aim of the present study was to investigate the predictive value of cTnT in samples from predialysis patients and to investigate associations between cTnT and inflammatory markers, such as C-reactive protein (CRP) and interleukin-6 (IL-6). DESIGN: Cohort, follow-up study. SETTING: Huddinge University Hospital, Sweden. SUBJECTS: A total of 115 (62% males, 28% diabetic patients) end-stage renal disease (ESRD) patients (52 +/- 1 years), of which 29% had cardiovascular disease (CVD), were studied shortly before the onset of dialysis therapy. Sixty-four patients started peritoneal dialysis (PD) as renal replacement therapy, whilst 49 started HD during the follow-up. MAIN OUTCOME MEASURES: The cTnT was analysed with the third generation TnT assay on Elecsys 2010. The prognostic value was calculated for cTnT, IL-6, age, CVD, malnutrition, diabetes mellitus (DM) and gender. Survival analyses were made with Kaplan-Meier and Cox regression analyses, with all-cause mortality as the clinical end point (mean follow-up period 2.7 +/- 0.1 years). RESULTS: Significant correlations were found between cTnT and CKMB (rho = 0.52, P < 0.0001), IL-6 (rho = 0.23, P < 0.05), CRP (rho = 0.30, P < 0.05), and serum albumin (rho = -0.31, P < 0.001), respectively. Diabetic patients had higher median serum cTnT level (0.09 microg L-1; range <0.01-0.51 vs. 0.04 microg L-1; range <0.01-0.67 microg L-1; P < 0.005) compared with nondiabetic patients. Likewise, patients with CVD had a significantly higher median level (0.08 microg L-1; range <0.01-0.67 microg L-1 vs. 0.04 microg L-1; range <0.01-0.61 microg L-1; P < 0.01) of cTnT compared with patients without CVD. Patients with cTnT > or =0.10 microg L-1 had a higher cumulative mortality rate than patients with cTnT < 0.10 microg L-1 (chi2 = 7.04; P < 0.01). Whilst age, CVD, malnutrition, DM, IL-6, cTnT and male gender were associated with poor outcome in the univariate analysis, only DM (P < 0.05) and cTnT (P < 0.05) were independently associated with mortality in a multivariate analysis. CONCLUSIONS: The present study demonstrates that serum concentrations of cTnT > or =0.10 microg L-1 is a significant predictor of mortality in patients starting dialysis. Moreover, the positive correlations between cTnT and IL-6, and CRP, respectively, suggest an association between inflammation and cTnT levels. Finally, the results of the present study suggest that cTnT is an independent predictor of mortality in ESRD patients starting dialysis.

Importance of preanalytical handling of samples for measurement of cardiac troponin T in coronary effluent from isolated rat hearts.

The isolated, buffer-perfused heart is probably the most widely used model in experimental heart research, and the coronary effluent is often analysed for markers of myocardial injury. Adsorption to surrounding materials may be a serious problem of protein measurements in solutions with low protein concentrations. The aims of the present study were to investigate the importance of the preanalytical phase when measuring cardiac troponin T (cTnT) in a buffer perfusate and to investigate whether addition of albumin to the effluent might increase recovery of cTnT and improve the assay. Coronary effluent was collected in tubes of different materials and in tubes with 40 g/L bovine albumin, and then frozen. cTnT was analysed at different time points after withdrawal from the freezer. cTnT was 2.3-119 times higher in effluent with albumin. In effluent without albumin, cTnT concentration declined to 2% of the initial concentration after two episodes of freezing and thawing. The cTnT loss could not be prevented by using polystyrene or siliconized glass, but was partially inhibited in effluent with albumin. Furthermore, creatine kinase and lactate dehydrogenase levels were higher in effluent with albumin. The within-series coefficient of variation for cTnT was markedly improved when using effluent with albumin.

New reference values for routine blood samples and human neutrophilic lipocalin during third-trimester pregnancy.

Reference values are usually based on blood samples from healthy men or non-pregnant women. Blood samples from pregnant women may be compared with these reference values. Correct references for pregnancy can be extremely important for clinical decisions such as ablatio placentae, appendicitis, premature rupture of membranes and preeclampsia. Previous studies of normal variations during third-trimester pregnancy are incomplete. Blood samples during pregnancy weeks 33, 36 and 39 as well as 1-3 h postpartum were collected from pregnant women with dietary iron supplement and at least one previous pregancy without a history of hypertension or preeclampsia. When the sampled values were compared with the present reference values from men and non-pregnant women, the following differences were found during normal pregnancy: Haemoglobin and ferritin were reduced, CRP was slightly elevated, WBC (white blood cell count) and HNL (human neutrophilic lipocalin) were elevated during pregnancy and significantly increased postpartum. Albumin was reduced. ALT and AST were slightly elevated and GGT was unchanged during pregnancy. ALP, D-dimer and fibrinogen were elevated. Uric acid increased during the third trimester and thrombocyte count decreased. Separate reference values for pregnant women are essential for correct diagnostic decisions during third-trimester pregnancy. Elevated levels of D-dimer do not necessarily indicate ablatio placentae. A diagnosis of progressive preeclampsia cannot be based on increasing uric acid levels and reduced platelet count in a stable clinical condition. HNL signals activation of neutrophilic granulocytes and can thereby offer a helpful tool for diagnosing infection during pregnancy and postpartum.

Increased cardiac troponin T and endothelin-1 concentrations in dialysis patients may indicate heart disease.

BACKGROUND: Cardiac troponin T (cTnT) is a highly sensitive marker for the detection of myocardial damage. However, patients maintained on chronic dialysis often have increased serum cTnT concentrations without evidence of acute myocardial injury. The reason for this is unclear. In chronic haemodialysis patients, elevated plasma concentrations of big endothelin-1 (big ET-1) and endothelin-1 (ET-1) have been reported which may be associated with ischaemic heart disease. The aim of the present study was to investigate possible associations between cTnT, big ET-1, ET-1, other cardiac markers and cardiac disease in dialysis patients. METHODS: Thirty-six haemodialysis (HD) patients and 26 peritoneal dialysis (PD) patients without symptoms of acute myocardial ischaemia were investigated. In all patients, serum concentrations of cTnT (2nd generation ELISA), cardiac troponin I (TnI) (Opus, Behring), creatine kinase MB (CKMB) mass and creatine kinase (CK) were determined, in HD patients before and after dialysis. Additionally, in HD patients, plasma ET-1 and big ET-1 were measured. In 27 HD patients, left ventricular mass index (LVMI) was determined. Patients with ischaemic heart disease (IHD) were compared with non-IHD patients. RESULTS: Serum cTnT was elevated (> or =0.10 microg/l) in 20 of 36 HD patients and in eight of 26 PD patients. cTnI was elevated (> or =0.5 microg/l) in four of 62 dialysis patients. HD+PD patients with IHD showed higher cTnT than HD+PD patients without IHD, and ET-1 concentrations were higher in HD patients with than without IHD. In HD patients, there was a positive correlation between cTnT and big ET-1. In HD patients with left ventricular hypertrophy (LVH), serum cTnT, CKMB mass and post-dialysis plasma big ET-1 were higher than in patients with normal LVMI. Furthermore there was a positive correlation between cTnT levels and LVMI. CONCLUSION: These findings suggest that circulating cTnT may reflect left ventricular hypertrophy and/or myocardial ischaemia in dialysis patients, and indicate that ET-1 and big ET-1 might be associated with these conditions.

Vasopressin and cortisol levels in response to glycine infusion.

The plasma vasopressin and serum cortisol concentrations were recorded in 7 healthy volunteers receiving an intravenous infusion of 1 l of isosmotic (2.2%) glycine solution during 20 min. The infusion elicited a significant increase in the plasma vasopressin level by a mean of 60% (SEM 13) above baseline level. The serum cortisol level increased only in the patient who developed signs of glycine toxicity. These results suggest that a glycine solution has water-retaining properties by stimulating the vasopressin secretion but usually not by increasing cortisol secretion.

Intravenous infusion of irrigating fluids containing glycine or mannitol with and without ethanol.

Irrigating fluids consisting of 5% mannitol, 3% mannitol + 1% ethanol, 2.2% glycine and 1.5% glycine + 1% ethanol in water were given by intravenous infusion to seven healthy volunteers at a constant rate of 50 ml./min. over 20 min. The irrigants containing glycine produced hyperkalemia and usually prickling and burning skin sensations and slight nausea. The severity of the symptoms apparently correlated to the blood ammonia level, which increased significantly after the glycine but not after the mannitol infusions. With 5% mannitol, there was a pronounced transient increase of the blood volume and a prolonged hyponatremia. There were no differences between the irrigants in respect to their effects on blood pressure and urine excretion. Ethanol caused no adverse effects and allowed the fluid supplementation to be followed by expired breath tests.

Detection of specific binding of [1,6-3H]2,3,7,8-tetrachlordibenzo-p- dioxin ([3H]TCDD) in human leukocytes using electrofocusing in polyacrylamide gel.

The binding of [1,6-3H]2,3,7,8-tetrachlorodibenzo-p-dioxin ([3H]TCDD) in human leukocyte cytosol has been studied using electrofocusing in polyacrylamide gel. One single peak of bound [3H]TCDD is found after completed focusing with an isoelectric point of 6.0. The binding capacity for 1.5 nM [3H]TCDD in the leukocyte cytosol was completely saturated by incubation in the presence of 150 nM unlabelled 2,3,7,8-tetrachlorodibenzofuran. [3H]TCDD also binds to a single binding species in human serum and plasma which focuses at pH 5.2 and which is not saturated by the addition of a 100-fold excess of unlabelled 2,3,7,8-tetrachlorodibenzofuran to the incubation. The levels of specific binding of [3H]TCDD in leukocytes from healthy blood donors ranged from 0 to 50 fmol/mg cytosolic protein.

Prolactin in cluster headache: diurnal secretion, response to thyrotropin-releasing hormone, and relation to sex steroids and gonadotropins.

The diurnal rhythmicity of serum prolactin (PRL) and the PRL and thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) were studied in 31 cluster headache patients (4 chronic cases) and 14 healthy controls. Sixteen of the patients were studied both during clinical remission and headache periods. In males the nocturnal PRL peak was blunted during remissions as compared with that in cluster periods and that in control individuals. The 24-h mean PRL levels were lower during remission and cluster periods than in the controls. There were no significant differences in the PRL levels between female patients and controls. Headache attacks were often associated with increases of serum PRL levels. The PRL response to TRH was lower in the female patients but not in the male patients as compared with controls. The maximum testosterone levels were lower during cluster periods than during clinical remission but not when compared with controls. Serum levels of luteinizing hormone, follicle-stimulating hormone, progesterone, estradiol, T3, T4, and TSH did not differ between patients and controls. The results suggest an altered regulation of PRL secretion not only during active cluster periods but also during symptom-free intervals. The possible influence of sleep, estradiol, testosterone, medication, pain, and serotoninergic and dopaminergic mechanisms are discussed.

Circadian secretion of cortisol and melatonin in cluster headache during active cluster periods and remission.

The cyclic nature of cluster headache warranted a study of the 24-hour rhythms of serum cortisol and melatonin. They were both altered during cluster periods as compared with periods of remission and healthy controls. The 24-hour mean and maximal cortisol levels were higher and the timing of the cortisol minimum was delayed as compared to the same patients in remission. Although there was no relation between the cortisol and melatonin levels and headaches, the rise of cortisol following many attacks might in part represent an adaptive response to pain. The nocturnal melatonin maximum was lower during cluster periods than in remission. This finding, and the dysautonomic signs during attacks, may reflect a change of the vegetative tone in a hyposympathetic direction.

Serum prolactin assays have no prognostic value in treatment of prostatic cancer by orchidectomy or estrogens.

Eighty patients (54-75 years) with cytologically and/or histologically confirmed cancer of the prostate (CAP) were randomly allocated to either orchidectomy (ORX, n = 41) or combined intramuscular and oral estrogen treatment (ESTR, n = 39). Serum levels of prolactin (PRL) were determined prior to treatment and 6, 12 and 24 months after initiation of the treatment. In the ORX group, 32 patients responded to the treatment and 9 did not. In the ESTR group, 27 patients responded and 12 did not. Serum PRL levels were significantly increased by ESTR treatment in responders as well as in nonresponders, but were not affected by ORX. There were no differences in PRL values between responders and nonresponders at any time in any of the two treatment groups. It is concluded that serum PRL assays have no prognostic value in the employed endocrine treatment of CAP.

Quantitation of estrogen receptor in seventy-five specimens of breast cancer: comparison between an immunoassay (Abbott ER-EIA monoclonal) and a [3H]estradiol binding assay based on isoelectric focusing in polyacrylamide gel.

Quantitation of estrogen receptor has been performed in cytosol prepared from 75 specimens of breast cancer tissue from patients who had not received hormonal therapy. The study was performed in order to compare an immunoassay (Abbott Laboratories, North Chicago, IL) with our currently used method for estrogen receptor analysis based on isoelectric focusing of [3H]estradiol-receptor complex in polyacrylamide gels. Using linear regression analysis, a regression coefficient (slope) of 1.30 and a correlation coefficient of 0.75 were calculated. The differences in results between the two methods are probably partly explained by the fact that the ligand-based method only measures unoccupied receptor, whereas the immunoassay detects the total amount of receptor, resulting in generally slightly higher concentrations with the latter method. However, in five of 75 specimens the ligand-based method gave a considerably higher concentration of estrogen receptor. This was most probably explained by partial proteolysis resulting in the formation of receptor fragment(s), which was undetectable with the immunoassay but detectable with the ligand-based method. These observations underline the importance of careful handling of specimens during the whole immunoassay procedure.

Influence of orchidectomy or oestrogen treatment on serum levels of pregnancy associated alpha 2-glycoprotein and sex hormone binding globulin in patients with prostatic cancer.

Peripheral serum levels of testosterone, immunoreactive oestrogens (E2), FSH, LH, prolactin and growth hormone (hGH) and two steroid-sensitive proteins, 'pregnancy-associated alpha 2-glycoprotein' (alpha 2-PAG) and sex hormone binding globulin (SHBG), were measured in patients with prostatic cancer before treatment and after orchidectomy or during combined oral and intramuscular oestrogen treatment. Following orchidectomy, the serum levels of testosterone and E2 decreased whilst the levels of FSH and LH increased significantly. No changes were noted in the serum levels of alpha 2-PAG, SHBG or prolactin. Oestrogen treatment significantly decreased the serum levels of testosterone, FSH and LH whilst levels of alpha 2-PAG, SHBG and prolactin were increased significantly. Serum levels of hGH during oestrogen treatment were significantly higher than in patients subjected to orchidectomy. These data are at variance with the established dogma of the oestrogen/androgen balance as a physiological regulator or liver protein synthesis, and indicate that factors other than the endogenous steroids may be operative. hGH may play an important role in this respect.

Pregnancy-associated glycoprotein (alpha 2-PAG)--a possible marker in breast cancer?

Serum levels of pregnancy-associated alpha-glycoprotein (alpha 2-PAG) and estradiol-17 beta (E2) and the estrogen receptor content (ER) in the tumor cytosol were measured in 174 women aged 24 to 94 years with primary breast cancer and the values were related to patient age, tumor size and clinical stage. While E2 levels were significantly lower and ER values significantly higher in older women, no significant correlation was found between alpha 2-PAG on one hand and the patients' age, E2 or ER values or tumor size on the other. A significant positive correlation (p = 0.016, Pearson correlation test) was found between alpha 2-PAG values and the clinical stage of the tumor. The results suggest the possible use of alpha 2-PAG as a marker for the monitoring of disseminated breast cancer during systemic therapy.

Validation of radioimmunoassay for estradiol-17 beta by isotope dilution-mass spectrometry and by a test of radiochemical purity.

Isotope dilution-mass spectrometry (ID-MS) was used as a reference method to determine the concentration of estradiol-17 beta (E2) in five different plasma pools (concentrations ranging from 0.040 to 65 nmol/l). The same plasma pools were also subjected to radioimmunoassay (RIA) using five different antisera of largely varying specificity. With the best antiserum (E), a direct RIA apparently gave accurate results (i.e. results statistically indistinguishable from those obtained by ID-MS) at all levels except the lowest one (0.040 nmol/l). It was shown, however, that the apparent accuracy of this RIA to some extent could be due to a lowering effect of lipids in the serum masking a lack of specificity of the antibodies. With the least specific antiserum (A), accurate results were obtained only after chromatography. However, in the assay of the lowest concentration of E2 with this antiserum there was a significant overestimation, even after chromatography. The other three antisera (B, C, D) of average quality gave accurate results in assays of plasma diethyl ether extracts in various numbers of the plasma pools tested, depending on their intrinsic specificity. This specificity was not correlated with the cross-reaction reported for individual antisera. ID-MS is difficult to use in most laboratories. We demonstrate here that the validity of a RIA may in this case be assessed by a relatively simple method, the test of radiochemical purity (RP-test). This test is based on the measurements of specific activity (e.g. dpm/pg) in small consecutive fractions of the chromatographic zone which is usually employed for the RIA.

Relationship between mammographic pattern and estrogen receptor content in breast cancer.

The mammographic pattern and its relationship to the estrogen receptor (ER) content was studied in 184 breast cancers. The tumors were divided into five radiographic subgroups: mass with spicules (A), diffuse (B), clusters of calcifications without a mass (C), circumscribed (D), and not visible at mammography (E). The ER content of tumors belonging to group A was higher than that of the other subgroups in both pre- and postmenopausal women. 121 tumors belonged to group A, of which 80% were ductal cancers. The tumors in groups B and C had very low ER values and those of groups D and E had intermediate values. The likelihood of finding a high estrogen receptor content of a tumor is thus greater when the tumor radiographically is seen as a mass with spicules than when seen as an increased attenuation or as only clusters of calcifications. It is suggested that patients with tumors belonging to group A should have a more favorable prognosis than patients with tumors belonging to groups B and C.