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The classical risk factors, hypercholesterolemia, smoking, hypertension and diabetes, explain only a part of the epidemiological features of atherosclerotic coronary heart disease. Investigations in the past few years have shown involvement of immunological mechanisms in atherosclerosis. Circulating immune complexes accelerate atherosclerosis both in experimental animal models and in humans. The fourth component of complement (C4) plays an important role in the solubilisation and elimination of immune complexes. C4 consists of two allotypes, C4A and C4B. An earlier report showed an association between C4B null alleles (C4B*Q0) and myocardial infarction and to infarction related mortality. In the present investigation, C4A*Q0 and C4B*Q0 were studied in two population samples. The first (Group I) was a cross sectional study of 100 consecutive males with myocardial infarction before the age of 45 years and 164 population based healthy controls, age and sex matched. The second (Group II) was a nested case control study in which a cohort of 50 year-old males were followed for 20 years for development of myocardial infarction between 50-60 and 60-70 years, and the results compared with those who did not develop MI. We observed no association of homozygous and/or heterozygous C4A*Q0 or C4B*Q0 with myocardial infarction occurring in the age groups45, 50-60 and 60-70 years or with the infarction related mortality (P0.05). The prevalence/frequency of C4A*Q0 and C4B*Q0 was not related to the age at which MI occurred. The prevalence of C4A*Q0 was not affected by age. We thus conclude that partial deficiency of C4 does not appear to be a major risk factor for myocardial infarction.

Thirty-two women with polycystic ovary syndrome (PCOS) were allocated to two antiandrogen treatment regimens; 28 women completed the trial. Twenty women were treated with ethinyloestradiol and cyproterone acetate (EO-CA) cyclically for 6 months and eight women were treated with the gonadotrophin releasing hormone (GnRH) analogue, goserelin for 6 months. Effects on hirsutism, insulin sensitivity (estimated by glucose clamp technique), blood lipids and hormones were measured. Women treated with EO-CA showed a reduction in hirsutism (P

As muscle tissue constitutes a main target organ for glucose metabolism and is responsible for the development of insulin resistance, it seems plausible to elucidate the relationship between blood pressure and muscle morphology and metabolism. The association between blood pressure and capillarization/morphology of the vastus lateralis muscle and metabolic variables was evaluated in 24 perimenopausal obese women [body mass index (BMI) 34.9 +/- 1.1; waist-hip ratio (WHR) 0.90 +/- 0.02]. The muscle enzyme activity of lipoprotein lipase (LPL), citrate synthase and glycogen synthase was determined. There was a significant negative correlation between the percentage of type I fibres and relative fibre area of type I on the one hand and systolic and diastolic blood pressure on the other. There was a negative correlation between the capillary density (i.e. number of capillaries/muscle fibre) and a positive correlation between the diffusion distance (fibre area supplied by one capillary) and diastolic blood pressure. The activities of LPL and citrate synthase were positively correlated with the percentage of type I and negatively correlated with the percentage of type II muscle fibres. The activity of LPL was also negatively correlated with plasma glucose and the insulin/C-peptide ratio. The insulin/C-peptide ratio was positively correlated with the percentage of type II muscle fibres. In stepwise multiple regression analyses, 20-30% of the variation in systolic and diastolic blood pressure could be explained by the variables of muscle fibre distribution. Excluding muscle morphological variables from the regression model, the insulin/C-peptide ratio accounted for 13% of the variation in systolic and diastolic blood pressure. The results of the study show the close association between muscle morphology and blood pressure. It remains to be elucidated whether this association indicates a causal relationship.

The monoclonal immunoglobulin (Ig) (M-component) secreted by the tumour plasma cells in multiple myeloma (MM) has specific antigenic determinants (idiotypes; id) that can serve as tumour-specific antigens. The intact Ig molecule is a weak antigen, and small fragments of id protein might be more immunogenic for the induction of id-specific immunity. Dendritic cells (DC) have attracted attention as the most efficient antigen-presenting cells and promising adjuvants for immunotherapy in tumours. In this study the in vitro T-cell response against F(ab')2 and Fab fragments, heavy and light chains of the M-component was examined in five patients with MM clinical stage I. All fragments were able to stimulate T cells but F(ab')2 or Fab fragments and heavy chains induced a stronger response than light chains. DC induced a significantly stronger id-specific immune response than monocytes. Moreover, with DC as antigen-presenting cells, a predominant interferon (IFN)-gamma (type-1 T-cell) response was seen in all patients. Both IFN-gamma and interleukin (IL)-4 (type-1 and type-2 T-cell) responses were noted when monocytes were used. Our study suggests that DC pulsed with idiotypic fragments such as F(ab')2 fragment and heavy chain can be used for the induction of type-1 anti-idiotypic T-cell response for immunotherapy in MM.

Myeloma plasma cells constitute 10% to 90% of the total bone marrow cell count in patients with multiple myeloma (MM). These cells express a variety of cell surface markers, such as HLA-ABC and HLA-DR, and surface antigens that are necessary for professional antigen-presenting cells, including adhesion and costimulatory molecules. In this study, we examined the expression of major histocompatability complex (MHC) and costimulatory molecules on CD38(bright,++) plasma cells in bone marrow aspirates from eight MM patients. Small percentages of plasma cells expressed weak but detectable levels of HLA-DR, HLA-DQ, CD40, CD80, and CD86, which could be upregulated by interferon-γ (IFN-γ) and tumor necrosis factor-α. CD38++ plasma cell and CD38(dim,+) cells were sorted from freshly isolated bone marrow mononuclear cells and tested for their capacity to act as antigen-presenting cells. Indeed, both CD38++ plasma cells and CD38+ cells were able to stimulate allogeneic T cells and present the soluble antigens purified protein derivative and tetanus toxoid to autologous T cells. Recognition of the antigens led to T-cell proliferation and secretion of IFN-γ and was MHC class-I and -II restricted. Antigen processing and presentation by CD38++ and CD38+ cells were abolished by treatment of the cells with chloroquine. Hence, our study provides for the first time evidence that myeloma plasma cells may act as antigen-presenting cells. Further studies are warranted to examine in detail the molecules required for inducing T-cell stimulation.

Hyperandrogenicity in women is closely associated with insulin resistance and a risk factor for cardiovascular disease and noninsulin-dependent diabetes mellitus (NIDDM). Therefore, 25 postmenopausal women with NIDDM and sex hormone-binding globulin values less than 60 nmol/L, as an indicator of a moderate hyperandrogenicity, were treated with 2 mg 17-beta-estradiol orally for 3 months in a double-blind, cross-over, placebo-controlled trial. During the last 16 days of active treatment, 1 mg norethisterone acetate was added for 10 days for endometrial protection. Blood glucose, glycosylated hemoglobin, insulin, c-peptide, lipoprotein profile, sex steroid hormones, GH, and insulin-like growth factor I (IGF-I) were measured, and insulin sensitivity was determined by the euglycemic hyperinsulinemic clamp method. All metabolic measurements were taken at baseline and after 68 days of active or placebo treatment. Estradiol treatment, compared with the placebo period, was followed by a marked increase of sex hormone-binding globulin and a decrease of free testosterone. Blood glucose, glycosylated hemoglobin, c-peptide, total cholesterol, low-density lipoprotein cholesterol, and IGF-I decreased significantly (P < 0.01-P < 0.001), whereas high-density lipoprotein cholesterol rose (P < 0.001). In conclusion, estrogen replacement therapy in postmenopausal women with NIDDM ameliorated hyperandrogenicity, and this was accompanied by marked improvements in glucose homeostasis and lipoprotein profile.

Tumour-specific CD4 + T helper (Th) and CD8 + T cytotoxic (Tc) cells may participate in the control and eradication of tumour cells. In the present study, idiotype-specific stimulation of CD4 + and CD8 + blood T cells from patients with monoclonal gammopathy of undetermined significance and patients with untreated multiple myeloma stage I was examined. Activation was measured in the CD4 + and CD8 + subsets enriched by magnetic microbeads as the incorporation of 3 H-thymidine and the secretion of interferon (IFN)-γ, interleukin (IL)-2 and IL-4 by single cells using the enzyme-linked immunospot assay. Idiotype-specific T cells were found in four of seven patients. Stimulation was mainly confined to the CD4 + subset in three of the four responding patients. This type of response was major histocompatibility complex (MHC) class II restricted as it could be inhibited by monoclonal antibodies against MHC class II (HLA-DR), but not against class I (HLA-ABC) molecules. Idiotype-specific CD8 + T cells were also demonstrated in these patients although at a lower frequency. One patient showed a strong and dominating activation of CD8 + T cells which could be blocked by antibodies against HLA-ABC but not against HLA-DR. Idiotype-specific CD4 + or CD8 + T cells were mainly of the type-1 subsets as judged by their secretion of IFN-γ and IL-2. Thus, this study provides evidence for the presence of idiotype-specific and MHC-restricted CD4 + and CD8 + T cells of the type-1 subsets in patients with monoclonal gammopathies. Such T cells with the potential to control the growth of tumour B cells may be a suitable target for immunotherapeutic interventions in patients.

The insulin-dependent diabetic patient is at greatly increased risk of premature atherosclerosis. Oxidative damage to lipoproteins has been implicated as an important factor in the atherogenic process. Diabetic patients are exposed to excessive oxidative stress because of non-enzymatic glycation of proteins and a variety of defects in antioxidant systems. We have previously described an enhanced chemiluminescent method for measuring protective ‘chain-breaking’ antioxidant activity in plasma lipoprotein fractions. In this study we compare the lipid content and antioxidant activity of plasma lipoproteins in 22 young insulin-dependent diabetics without vascular complications and 20 age- and sex-matched controls. Mean levels of haemoglobin A1c in the diabetic group were 8.890.2%. There were no significant differences in serum total cholesterol, apolipoprotein A, apolipoprotein B or lipoprotein(a) levels between the study groups. Serum total triglyceride levels (1.329 0.11 versus 1.0190.08 mmol:l; PB0.05) and LDL-associated triglyceride (0.289 0.04 versus 0.159 0.02 mmol:l; PB 0.05) were significantly elevated in the diabetic group. Total plasma antioxidant activity was significantly reduced in the diabetic group (272.09 15.4 versus 338.3920.7 mmol:l; PB0.05). Antioxidant activity measured in five lipoprotein fractions isolated by density gradient ultracentrifugation (VLDL1, VLDL2, LDL1, LDL2 and HDL) showed no significant differences between groups when corrected for protein, total lipid or cholesterol content. When corrected for triglyceride content significantly lower antioxidant values were found in the diabetic HDL fraction only. The results of this study imply that the susceptibility of the insulin-dependent diabetic to the development of premature atherosclerosis cannot be attributed to reduced antioxidant activity in circulating plasma lipoproteins. © 1997 Elsevier Science Ireland Ltd.

Background Women with polycystic ovary syndrome (PCOS) have symptoms of depression and anxiety and impaired health related quality of life (HRQoL). Here we test the post-hoc hypothesis that acupuncture and exercise improve depression and anxiety symptoms and HRQoL in PCOS women. Methods Seventy-two PCOS women were randomly assigned to 16 weeks of 1) acupuncture (n = 28); 2) exercise (n = 29); or 3) no intervention (control) (n = 15). Outcome measures included: change in Montgomery Åsberg Depression Rating Scale (MADRS-S), Brief Scale for Anxiety (BSA-S), Swedish Short-Form 36 (SF-36), and PCOS Questionnaire (PCOSQ) scores from baseline to after 16-week intervention, and to 16-week post-intervention follow-up. Results A reduction in MADRS-S and BSA-S from baseline to 16-weeks post-intervention follow-up was observed for the acupuncture group. The SF-36 domains role physical, energy/vitality, general health perception and the mental component of summary scores improved in the acupuncture group after intervention and at follow-up. Within the exercise group the role physical decreased after treatment, while physical functioning and general health perception scores increased at follow-up. The emotion domain in the PCOSQ improved after 16-weeks of intervention within all three groups, and at follow-up in acupuncture and exercise groups. At follow-up, improvement in the infertility domain was observed within the exercise group. Conclusion There was a modest improvement in depression and anxiety scores in women treated with acupuncture, and improved HRQoL scores were noted in both intervention groups. While not a primary focus of the trial, these data suggest continued investigation of mental health outcomes in women treated for PCOS. Trial registration number ClinicalTrials.gov Identifier: NCT00484705

SUMMARY An important and yet unresolved question concerns the mode of T cell recognition of idiotypic epitopes on immunoglobulin molecules in humans. Results from murine and human studies show that some idiotype-specific T cells recognize conformational epitopes on immunoglobulin, and such T cells are not MHC-restricted. In the present study T cell stimulation induced by idiotypic determinants on the autologous monoclonal IgG (M-components) from patients with monoclonal gammopathies was studied. In parallel, T cell stimulation in response to a conventional antigen, purified protein derivative, was also examined. It is shown that, as with conventional antigen, idiotype-induced T cell stimulation requires the presence of antigen-presenting cells (APC; monocytes and/or B cells), and is MHC class II (DR)-restricted. B cells, but not monocytes, can present idiotypic determinants to T cells at very low antigen concentrations, while monocytes do so only when antigen is present at high concentrations. Antigen processing and presentation is abrogated by treatment of APC with chloroquine. In conclusion, our study demonstrates that human idiotype-specific T cells recognize processed idiotypic determinants presented by MHC class II (HLA-DR) molecules on APC, and that B cells require about 1000-fold less antigen than monocytes.

Oxidized low density lipoproteins (oxLDL) stimulated human blood T cells to a specific cytotoxic response which autologous PHA activated blood mononuclear cells which had been pre-incubated with oxLDL. The cytotoxic reaction was exerted by CD8+ enriched cells but not by CD4+ enriched cells. Allogeneic target cells from HLA mismatched donors were not damaged and the reaction was consistently inhibited by monoclonal antibody against HLA class I. Antigen-specific cytotoxic T cells might contribute to lysis of cells in the atherosclerotic plaque that have taken up oxLDL and thus participate in the inflammatory process associated with atherosclerosis.

Background : The optimal number of chemotherapy courses in responding patients with advanced-stage Hodgkin's disease (HD) is unknown. Patients and methods : With minimizing chemotherapy and thereby reducing late complications as the objective, patients with advanced HD were randomized to receive either 4 full MOPP/ABVD courses or treatment up to complete remission (CR). Forty-seven patients were given the fixed (FT) and 41 patients the individual treatment (IT). The two groups were balanced according to age, histopathology and sex, although stage IVB dominated in the IT group (20 vs. 8). Results : Sixty-six of 88 patients (75%) achieved CR. No difference between the two treatment groups in the proportion of stage IVB patients was seen when those achieving CR, i.e., the efficacy population were compared. The mean number of single chemotherapy courses given was 3.7 of MOPP and 3.5 of ABVD in the FT group, compared to 2.6 of MOPP and 2.5 of ABVD in the IT group (p < 0.001). The predicted progression-free survival at 10 years was 81% in the FT and 68% in the IT arm, respectively (p < 0.05). No statistically significant difference in cause-specific 10-year survival was observed (82% and 83%, respectively ; p = 0.18). Long-standing CRs were achieved following minimal chemotherapy. Conclusions : Since there are no available methods to identify long-term disease-free survivors among CR patients following a limited induction treatment, we suggest that the policy of giving 3-4 full MOPP/ABVD courses should continue. The price for such an approach is the overtreatment of a subset of already cured patients.

Objectives. To investigate the prevalence of anti-cardiolipin and antiendothelial cell antibodies in patients operated on for atherosclerotic peripheral vascular disease before 50 years of age. The hypothesis to be tested was whether antibodies associated with an immune/inflammatory damage to the vascular wall were associated also with early atherosclerosis. Design. A case-control study. Setting. Departments of surgery and an immunological research laboratory, and routine laboratories of two tertiary referral hospitals. Subjects. All patients operated for atherosclerotic peripheral vascular disease before 50 years of age. Sixty-two patients (33 males, 29 females), and 67 age- and sex-matched controls participated. The diagnosis of atherosclerosis was made on the basis of the clinical presentation and angiographic visualization of the diseased vasculature. Main outcome measures. Subjects were compared for the prevalence of anticardiolipin and antiendothelial cell antibodies, altered serum lipoprotein levels, smoking, diabetes, hypertension, and signs of inflammation. Results. Antibodies against endothelial cells and cardiolipin were found in 12.9 and 14.5% of the patients, respectively, which was higher than observed in the control group (P < 0.05). Sixty per cent of patients with antibodies were females. Conventional risk factors were more often noted in the patient group. However, patients with antibodies against endothelial cell and/or cardiolipin had a lower prevalence of hyperlipidaemia/dyslipidaemia when compared to patients without these antibodies (P < 0.05). Conclusions. Antibodies against endothelial cells and cardiolipin are present in a subset of patients with clinical and angiographic diagnosis of severe premature atherosclerotic peripheral vascular disease. The lower occurrence of hyperlipidaemia/dyslipidaemia in patients with autoantibodies, in comparison to patients without the antibodies, suggests that these antibodies have a role in vascular damage.

The presence of idiotype-reactive T-cell subsets and their relation to the tumor load were analyzed in 9 patients with monoclonal gammopathy of undetermined significance (MGUS), in 12 patients with multiple myeloma (MM) clinical stage I, and in 9 patients with MM stage II/III. An enzyme-linked immunospot assay was used to identify interferon-gamma (IFN-gamma)-, interleukin-2 (IL-2)-, or IL-4-secreting T cells after stimulation by F(ab')2 fragments of monoclonal IgG. The response to autologous IgG was significantly higher than that induced by isotypic monoclonal IgG. Comparable results were obtained in a proliferation assay (3H-thymidine incorporation). A total of 8 of 9 patients with MGUS, 7 of 12 patients with MM stage I, and 3 of 9 with MM stage II/III had T cells secreting IFN-gamma and/or IL-2 (T helper [Th1] type-1 cells), whereas cells secreting both Th1 and Th2 or Th0 types of cytokines were more frequent in patients with MM, particularly in those with MM stage II/III. The number and frequency of Th1-type cells were significantly higher in MGUS patients as compared with those of MM stage II/III. The results indicate that idiotype-reactive T cells of the Th1 and Th2 or Th0 subsets were present in MGs and might provide indirect evidence that idiotype-reactive Th1-type cells may have a regulatory impact on the human tumor B cells.

In years to come, new therapeutic modalities for the treatment of chronic arthritis will be launched for general clinical use. These therapies, until today only used in clinical studies, are based on knowledge obtained from animal models of chronic arthritis. This knowledge not only ushers therapeutic use in humans: in many settings, the animal studies have proven to be irreplacable tools to get insights into the pathogenesis of chronic arthritis. Rheumatoid arthritis (RA) shows a strong linkage of susceptibility to a certain epitope common to some HLA-DR beta chains; this immunogenetic linkage is the strongest evidence for specific, T-cell dependent immunity in the pathogenesis of the disease. Despite intense efforts, no unequivocal proofs of T-cell specificity or oligoclonality have been found in RA. Therapeutic efforts directed against T-cells or T-cell functions have also at the best showed partial effects. As compared to the local production of T-cell cytokines in the joint, monokine production is abundant. Therapies aimed at neutralizing the effects of the cartilage-devastating monokine TNF-a have showed remarkable results in small clinical trials. The possibility of increasing the presence of the regulatory cytokines IL-4, IL-10 and TGF-beta has also been explored, but only in animal studies. Immunology has also shed light on the mode of action of the commonly used 'disease modifying' drugs, and combinations of such drugs have shown increased potentials in recent clinical studies. The possibility of combining traditional anti-arthritic drugs with recent immunological tools seem promising for the future. This review discusses recent advances in the understanding of pathogenesis and delineate new therapeutic approaches for chronic arthritis from the point of view of the immunologically oriented clinician.

Abstract One hundred patients who had survived a myocardial infarction before the age of 45 years and 90 age- and sex-matched healthy individuals were investigated for circulating immune complexes (CICs) and the presence of complement C4 null alleles (C4Q0). CICs were found in increased concentrations in 20% of patients and 6.7% of control subjects. Patients and control subjects had the same prevalence of C4Q0. CICs were present in all patients and in 36% of the control subjects homozygous for C4Q0. Patients and control subjects heterozygous for C4Q0 had CICs in 71% and 0%, respectively. The high prevalence and a high concentration of CICs were particularly associated with C4A*Q0. Patients homozygous for C4A*Q0 had concentrations of LDL that were lower than found in other patients. The increased concentration of CICs associated with genetic deficiencies of the complement factor C4 might thus be an additional etiological factor for the development of chronic vascular damage and premature myocardial infarction.

Idiotype-specific T cells were characterized in patients with multiple myeloma stage I by analysing idiotype-induced DNA synthesis (3H-thymidine incorporation), IL-2 and IFN-gamma production at the single cell level (ELISPOT) (in vitro tests) and delayed type hypersensitivity (DTH) skin reaction (in vivo test). In seven out of eight patients at least one of the four tests was positive. In five patients three or more tests were positive. One patient was negative in all four tests. Six patients had both IL-2 and IFN-gamma-secreting cells and three of them also a DTH response. Furthermore, those three patients with a proliferative response also had IL-2 and IFN-gamma-secreting cells induced by the idiotype. The data indicate that part of the idiotype-specific T cell fraction belongs to the CD4 Th1 cell population. Whether CD8-specific T cells also were present could not be ruled out. The present study provides further support for the existence of idiotype-specific T cells in multiple myeloma. Such cells might be an important target for an immune-mediated therapeutic approach.

The prevalence of peripheral blood B cells secreting antibodies reacting with the F(ab')2 fragment of monoclonal IgG was studied in five patients with multiple myeloma (MM), nine patients with monoclonal gammopathy of undetermined significance (MGUS) and six healthy controls. An enzyme-linked immunospot assay allowed direct visualization of antibody producing B cells. All patients had B cells producing antibodies to autologous or allogeneic monoclonal IgG. Autoreactive cells were found more frequently than alloreactive cells in seven out of nine patients with MGUS and three out of four patients with MM. The same frequency of alloreactive cells in the patient groups was detected in healthy individuals. These findings show the existence of B cells producing anti-idiotypic antibodies which could be a part of an idiotypic network in monoclonal gammopathies.

Visceral obese men were characterized by a decreased total GH secretion and diminished peak amplitude, size, and number. T-substitution was followed by elevation of IGF-I levels. The IGF-I increase correlated with the elevation of T-concentration, and was most pronounced in men with the lowest concentrations of free T from the outset. There were no detectable changes in total quantity, amplitude, size or number of peaks of GH secretion. Glucose, cholesterol and triglycerides as well as diastolic blood pressure decreased. There were no changes in thyroid or hematology variables. Visceral obesity in men has been reported to be characterized by low testosterone (T) and insulin-like growth factor I (IGF-I) concentrations, the latter suggesting a relative growth hormone (GH) deficiency. Since T and GH-secretions are interrelated, men with visceral obesity were substituted with T for 14 days, and diurnal secretion pattern of GH as well as IGF-I concentrations, and metabolic variables were followed. T-substitution of visceral obese men is followed by an elevation of IGF-I concentrations. It is suggested that this might be due either to minor, non-detectable increases in GH secretion, or to direct effects of T on IGF-I concentrations. The regulatory mechanisms by which T-administration are leading to metabolic and anthropometric improvements, might be direct effects of T, with or without mediation via GH secretion.

Objective: To investigate the possible effects of low-frequency electroacupuncture (EA) and physical exercise on markers of coagulation and fibrinolysis, insulin sensitivity, and adipose tissue characteristics in women with polycystic ovary syndrome (PCOS). Design: Secondary analyses of a prospective, randomized controlled clinical trial. Setting: Department of Physiology and Department of Obstetrics and Gynecology, University of Gothenburg. Patient(s): Eighty-four women with PCOS were randomized. Intervention(s): Women with PCOS were randomized to 16 weeks of low-frequency EA (14 treatments), physical exercise (at least 3 times/wk), or no intervention. Main Outcome Measure(s): Anthropometrics, circulating coagulation and fibrinolytic markers, insulin sensitivity (euglycemic hyperinsulinemic clamp), hemodynamics, and adipose tissue morphology/function recorded at baseline, after 16 weeks of intervention, and after a 16-week follow-up. Result(s): In the low-frequency EA group, circulating plasminogen activator inhibitor 1 activity decreased by 21.8% after 16 weeks of intervention and by 31.1% at the 16-week follow-up and differed from the physical exercise and the no intervention groups. The EA group had decreases in circulating fibrinogen and tissue plasminogen activator (t-PA), sagittal diameter, and diastolic blood pressure after treatment, and fibrinogen remained lower at the 16-week follow-up. In the physical exercise group, lipoprotein lipase activity increased and diastolic blood pressure decreased after treatment, and both diastolic and systolic blood pressure were lower at follow-up. No other variables were affected. Conclusion(s): Low-frequency EA counteracted a possible prothrombotic state in women with PCOS, as reflected by a decrease in plasminogen activator inhibitor 1 activity. Despite within-group improvements, there were no between-group differences in anthropometric, metabolic, or hemodynamic variables after 16 weeks of EA or physical exercise at the dose/intensity studied. (Fertil Steril(R) 2012;97:501-8. (C) 2012 by American Society for Reproductive Medicine.)

Background Orexin A and B are neuropeptides influencing, for example, arousal and respiration. Although panic disorder is characterized by both enhanced proneness for arousal and by respiratory abnormalities, the possible influence of orexin-related genes on the risk of developing this disorder has not been studied until now. Methods We have analyzed the Ile408Val polymorphism in the hypocretin receptor 1 (HCRTR1) gene and the Val308Iso (G1246A) polymorphism in the hypocretin receptor 2 (HCRTR2) gene in a sample of 215 panic disorder patients and 454 controls. Results Although the polymorphism in the HCRTR1 did not differ between groups, the Iso allele of the HCRTR2 polymorphism was significantly more frequent in patients than in controls. After the population was divided according to sex, the association between the Iso allele of the Val308Iso polymorphism and panic disorder was observed only in female patients. Conclusion Our results suggest that the HCRTR2 polymorphism may be of importance for the pathophysiology of panic disorder. The results should be regarded as preliminary until replicated in an independent sample. This indicates that further research on the possible role of orexin in panic disorder may prove rewarding.

The ecological phenomenon of arthropods with defensive hairs is widespread. These urticating hairs can be divided into three categories: true setae, which are detachable hairs in Lepidoptera and in New World tarantula spiders; modified setae, which are stiff hairs in lepidopteran larvae; and spines, which are complex and secretion-filled structures in lepidopteran larvae. This review focuses on the true setae because their high density on a large number of common arthropod species has great implications for human and animal health. Morphology and function, interactions with human tissues, epidemiology, and medical impact, including inflammation and allergy in relation to true setae, are addressed. Because data from epidemiological and other clinical studies are ambiguous with regard to frequencies of setae-caused allergic reactions, other mechanisms for setae-mediated disease are suggested. Finally, we briefly discuss current evidence for the adaptive and ecological significance of true setae.

The stimulation of peripheral blood mononuclear cells by purified autologous and/or allogeneic monoclonal IgG was studied in five patients with multiple myeloma (MM), nine patients with monoclonal gammopathy of undetermined significance (MGUS) and six healthy individuals. Single cells secreting IFN-γ or IL-2 were identified using an enzyme-linked immunospot assay. Patients' cells were preferentially stimulated by autologous monoclonal IgG at low concentrations (1–100 pg/ml). while l00 ng/ml or higher stimulated T cells both from patients and, to a lesser degree, healthy individuals. This biphasic dose-response of T-cell stimulation by autologous monoclonal IgG was reproduced in all patients. The numbers of cells secreting IFN-γ and IL-2 in response to allogeneic IgG were significantly lower than the numbers obtained using autologous IgG in patients with MM and MGUS. Cells from healthy individuals were stimulated by allogeneic monoclonal IgG, but to a lesser extent. The results of this study support the presence of idiotype-reactive T cells in patients with MM and MGUS and also may suggest a general but less pronounced T-cell reactivity to monoclonal IgG among these patients.

Multiple myeloma (MM) is a B-lineage malignancy with unknown aetiology. It has been considered that predisposing genetic factors might be implicated in the disease. In this study, the microsatellite polymorphism in the exon 3 of the cytotoxic T-lymphocyte antigen-4 (CTLA-4) gene was analysed in patients with MM and monoclonal gammopathy of undetermined significance (MGUS), together with ethnically matched healthy controls. The results showed that frequencies of the genotype 86/86 and of the allele 86 were significantly decreased in MM and MGUS compared with matched healthy controls, indicating that the CTLA-4 microsatellite polymorphism might represent a susceptibility locus for MM and MGUS.

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenism, oligo/amenorrhea, and polycystic ovaries. We aimed to determine whether low-frequency electro-acupuncture (EA) would decrease hyperandrogenism and improve oligo/amenorrhea more effectively than physical exercise or no intervention. We randomized 84 women with PCOS, aged 18–37 yr, to 16 wk of low-frequency EA, physical exercise, or no intervention. The primary outcome measure changes in the concentration of total testosterone (T) at week 16 determined by gas and liquid chromatography-mass spectrometry was analyzed by intention to treat. Secondary outcome measures were changes in menstrual frequency; concentrations of androgens, estrogens, androgen precursors, and glucuronidated androgen metabolites; and acne and hirsutism. Outcomes were assessed at baseline, after 16 wk of intervention, and after a 16-wk follow-up. After 16 wk of intervention, circulating T decreased by −25%, androsterone glucuronide by −30%, and androstane-3α,17β-diol-3-glucuronide by −28% in the EA group ( P = 0.038, 0.030, and 0.047, respectively vs. exercise); menstrual frequency increased to 0.69/month from 0.28 at baseline in the EA group ( P = 0.018 vs. exercise). After the 16-wk follow-up, the acne score decreased by −32% in the EA group ( P = 0.006 vs. exercise). Both EA and exercise improved menstrual frequency and decreased the levels of several sex steroids at week 16 and at the 16-wk follow-up compared with no intervention. Low-frequency EA and physical exercise improved hyperandrogenism and menstrual frequency more effectively than no intervention in women with PCOS. Low-frequency EA was superior to physical exercise and may be useful for treating hyperandrogenism and oligo/amenorrhea.

Mass, morphology, and metabolism of total adipose tissue and its subcutaneous, visceral, and retroperitoneal subcompartments were examined in 16 men with a wide variation of total body fat. Computerized tomography (CT) scans showed that the intraabdominal fat mass comprised approximately 20% of total fat mass. Visceral and retroperitoneal fat masses were approximately 80% and 20% of total intraabdominal fat mass, respectively. Enlargement of intraabdominal fat depots was due to a parallel adipocyte enlargement only. Direct significant correlations were found between these adipose tissue masses and blood glucose and plasma insulin levels, blood pressure, and liver function tests, while glucose disposal rate during euglycemic glucose clamp measurements at submaximal insulin concentrations (GDR), plasma testosterone, and sex hormone-binding globulin concentrations correlated negatively. The correlations for glucose, insulin, and GDR were strongest with visceral fat mass. Adipose tissue lipid uptake, measured after oral administration of labeled oleic acid in triglyceride, was approximately 50% higher in omental than in subcutaneous adipose tissues. Adipocytes from omental fat also showed a higher lipolytic sensitivity and responsiveness to catecholamines. Furthermore, these adipocytes were less sensitive to the antilipolytic effects of insulin. Both lipid uptake and lipolytic sensitivity and responsiveness showed strong correlations (r = 0.8 to 0.9) to blood glucose and plasma insulin concentrations and also to the GDR (negative), while no such correlations were found with lipid uptake in subcutaneous or retroperitoneal abdominal adipose tissues. Taken together, these results suggest a higher turnover of lipids in visceral than in the other fat depots, which is closely correlated to systemic insulin resistance and glucose metabolism in men.

Glucose disposal into muscle glycogen has previously been directly studied after intravenous, but not after physiological, oral administration. In this study 100 g glucose, containing 50 microCi [U-14C]glucose, were taken orally by premenopausal women in the overnight fasting state or after a carbohydrate-rich meal. After 4 h, biopsies were taken from the vastus lateralis muscle and abdominal and femoral subcutaneous adipose tissue for determinations of label in isolated glycogen and triglycerides, respectively. Uptake of administered glucose carbon in muscle glycogen was estimated to be approximately 20 g in the fasting and approximately 9 g in the carbohydrate-fed groups, respectively. Total uptake in adipose tissue triglycerides was approximately 2 g. Glucose carbon uptake in muscle glycogen correlated positively with glucose infusion rates during euglycemic hyperinsulinemic glucose clamps, glycogen synthase activity in vitro, and type I muscle fiber distribution and fiber area. Negative correlations were found between glucose uptake in adipose tissue triglycerides, type II fiber distribution and fiber area, as well as the waist-to-hip circumference ratio and degree of obesity. It was concluded that muscle glycogen is probably not a major pathway for disposal of oral glucose carbon in the sedentary condition.

BACKGROUND Anxiety and depression are more prevalent in women with polycystic ovary syndrome (PCOS) than in those without this disorder. Possible confounding effects of overweight and obesity are suggested. The aim was to compare symptoms of anxiety and depression in women with PCOS and controls matched for age, body weight and body mass index (BMI). METHODS Women with PCOS (n = 30) and controls (n = 30) were recruited from the community. Persons with ongoing psychotropic medication were excluded. All potential participants underwent gynecological examination to confirm case-control status. Participants completed the self-reported versions of the Brief Scale for Anxiety (BSA-S) and Montgomery Asberg Depression Rating Scale (MADRS-S). RESULTS Women with PCOS had a higher BSA-S score compared with controls (median, range: 10.5, 1-24 versus 5.0, 0-28, P < 0.001). They scored higher on the following four individual symptoms: reduced sleep (2.0, 0-5 versus 0, 0-2, P < 0.001), worry (1.5, 0-4 versus 0, 0-6, P = 0.004), phobias (1, 0-4 versus 0, 0-3, P < 0.001), and pain (1, 0-3 versus 0, 0-2, P < 0.001). No statistical difference was demonstrated regarding MADRS-S scores (10.0, 0-27 versus 5.5, 0-24, P = 0.053). Only one of the nine MADRS-S symptoms, reduced sleep, which is also included in the BSA-S, differed between cases and controls. CONCLUSIONS Several anxiety symptoms distinguished women with PCOS from a control group matched on BMI. A better understanding of the symptoms is needed to identify and alleviate anxiety symptoms in this vulnerable group.

In order to predict consequences of replacing jet grouting with biogrouting, and identify major contributors to the cost of both technologies, a large road project in Stockholm, Sweden, was used as a case study. Jet grouting had been used to seal the contact between sheet piling and bedrock, biogrouting for the same function was computed. A comparative environmental and economical assessment was carried out using life cycle assessment (LCA). The results show that biogrouting was cheaper than jet grouting and would have had lower environmental impact. The major difference was the transport and use of heavier equipment for jet grouting. Biogrouting also used less water and produced less landfilled waste. However, the production of urea and CaCl(2) for biogrouting required much energy.

B-lymphocyte clones bearing an idiotypic Ig structure, which could also be found on the serum M-component, have been isolated from peripheral blood of a patient with monoclonal gammopathy (MG) using an immune- rosetting technique and limiting dilution. The majority of the cells had the surface phenotype id+/CD19+/CD20+/CD21+ or id+/CD19+/CD20+/CD21- . Some of the clones originated from spontaneous outgrowth of lymphocytes and some were derived from in vitro Epstein-Barr virus- infected lymphocytes. Three of the B-lymphocyte clones and the patient's bone marrow plasma cells appeared to have clonal identity as shown by the same Ig heavy chain gene rearrangements in Southern blot analysis using a JH probe. The study further supports the notion that the peripheral blood of patients with MG contains B lymphocytes that belong to the tumor clone.

SUMMARY The oxidative metabolic burst of blood monocytes and polymorphonuclear leukocytes (PMN) from 22 untreated patients with Hodgkin’s disease (HD) and 18 healthy subjects were studied. Monocytes and PMN were enriched by density centrifugation and in vitro activated by zymosan. The oxidative metabolism was measured by luminol-enhanced chemiluminescence (CL). The CL of the patients’ monocytes and PMN was higher than that of controls (P< 0.01 and P± 0.05, respectively). Patients with stage II-IV HD showed an increased blood monocyte CL as compared with stage I patients (P

Seven men with well-controlled, noninsulin-dependent (type 2) diabetes ingested on two different mornings, in random order, meals with or without a 5.0-g sodium alginate supplement (algae-isolate, 75% soluble fiber). The meals contained similar amounts of digestible carbohydrates, fat and protein. The gastric emptying rate of the meal containing sodium alginate, measured by detection of 51Cr mixed into the meals, was significantly slower than that of the fiber-free meal. Sodium alginate also induced significantly lower postprandial rises in blood glucose, serum insulin and plasma C-peptide. The diminished glucose response after the addition of sodium alginate could be correlated to the delayed gastric emptying rate induced by the fiber (rs = 0.92, P less than 0.01).

Raised levels of inflammation markers have been associated with several mental disorders; however, studies regarding the relationship between inflammation or the immune system and various aspects of human behaviour are not numerous. The aim of the present study was to investigate whether an association exists between personality traits and two single nucleotide polymorphisms located in genes that are associated with the innate immune system. The studied population consisted of 42-year-old women recruited from the population registry that had been assessed by means of Karolinska Scales of Personality, a self-reported inventory. The first polymorphism, +1444C>T (rs1130864), is located in the gene coding for C-reactive protein (CRP), a marker of low-grade inflammation. The T-allele has previously been suggested to be linked to raised serum levels of CRP. The second polymorphism, Y402H (1277T>C, rs1061170), is located in the gene coding for complement factor H, an important regulator of the complement system. The C-allele has consistently been associated with age-related macular degeneration. While the +1444T allele was associated with higher scores in the personality traits impulsiveness, monotony avoidance and social desirability, the 1277C polymorphism was associated with higher scores in verbal aggression and lower scores in social desirability. In conclusion, the associations between the personality traits and the studied polymorphisms further support the possible influence of the immune system on mental functions.

Genetic factors have been shown to influence high-sensitivity C-reactive protein (hsCRP) levels, however, which genes that are involved in this process remains to be clarified. The renin–angiotensin system (RAS) is of importance for the regulation of inflammation, and blockade of angiotensin II type 1 receptors (AGTR1) influences hsCRP levels. These findings prompted us to investigate whether a polymorphism in the AGTR1 gene may influence hsCRP levels. Additionally, a polymorphism in the CRP gene that has previously been shown to influence hsCRP levels was genotyped. Serum levels of hsCRP were measured in 270 42-year-old women recruited from the population registry. Two single nucleotide polymorphisms were analysed: +1166A>C and +1444C>T of the AGTR1 and CRP gene, respectively. The A allele of the AGTR1 polymorphism +1166A>C was dose-dependently associated with higher hsCRP levels ( p = 0.014, adjusted for confounding factors and multiple comparisons). hsCRP levels were not significantly influenced by the CRP +1444C>T genotype; however, an interaction between the two studied polymorphisms with respect to hsCRP levels was observed ( p = 0.018). The significant association between the AGTR1 polymorphism and hsCRP levels, which appears to be independent of anthropometric and metabolic traits, is yet another indication of a direct influence of RAS on inflammation.

Untreated patients with Hodgkin's disease (HD) have a blood T- lymphocytopenia mainly caused by a reduction of the CD4+ subset. Indirect support for a sequestration of T cells in the spleen and tumor- involved lymphoid tissue has accumulated. To test the hypothesis that the blood CD4 T-lymphocytopenia in patients with HD is caused by an altered lymphocyte traffic, 12 untreated HD patients and five in complete clinical remission (CCR) were studied. Blood lymphocytes were collected by leukapheresis and gradient centrifugation, and were further purified by an adherence step. The cells were labeled with indium-111 oxine and reinfused intravenously into the patient. The radioactivity of CD4+ and CD8+ blood lymphocytes separated by immunoabsorption was measured from serial blood samples. CD4+ cells were eliminated more rapidly in untreated patients than patients in CCR. Repeated gamma camera imaging after autotransfusion of indium-111 oxine labeled cells demonstrated an accumulation of radioactivity in tumor-involved tissue of untreated patients. These findings support the concept of an enhanced elimination of CD4+ cells in patients with active HD that may contribute to the observed blood T-lymphocytopenia and may reflect a biologic response to the tumor.

To assess muscle function after a period of negative energy balance, 32 obese women were placed on a 544-kcal/d, high-protein diet for 4 wk. Weight loss was associated with a decrease in the waist-to-hip-circumference ratio (WHR) and significantly higher emptying of abdominal than gluteal fat cells. The low-calorie regimen was associated with a significant increase in isokinetic muscle endurance, a decrease in glycogen concentration, and an increase in glycogen synthase (GS) activity and its fractional velocity (FV). The GS activity and its FV were negatively correlated with the WHR before treatment whereas their subsequent increase was correlated with the decrease in WHR. Dietary treatment produced a decrease in the isokinetic muscle strength, which was correlated with the reduction in lean body mass. The improvement in dynamic endurance observed after energy restriction parallels not only the increase in GS activity in muscle but also the decrease in glycogen stores and glucose oxidation, and most probably depends on the increased utilization of fatty acids.

Catechol O-methyltransferase (COMT) degrades catecholamines and estrogens, both of which are of known importance for cardiovascular risk factors such as obesity and hypertension. The gene coding for COMT contains a val158-met polymorphism that exerts a considerable influence on enzymatic activity. We hypothesized that this polymorphism might influence risk factors for cardiovascular disease. Deoxyribonucleic acid samples and data regarding blood pressure and anthropometry were collected from 240 Swedish men, all 51 years old. Subjects homozygous for the low-activity allele (met) displayed higher blood pressure, heart rate, waist-to-hip ratio, and abdominal sagittal diameter as compared with heterozygous subjects, who in turn displayed higher blood pressure, heart rate, waist-to-hip ratio, and abdominal sagittal diameter than subjects homozygous for the high-activity allele (val). All measured variables were significantly correlated; however, the associations between COMT val158-met and cardiovascular variables, and the association between COMT val158-met and anthropometry, respectively, were partly independent of each other, as revealed by multiple linear regression.

In recent studies, the sequence of Kaposi's sarcoma-associated herpes virus (KSHV) or human herpes virus-8 (HHV-8) was detected in dendritic cells (DC) of patients with multiple myeloma (MM). A concern was raised whether there is an causal association between the viral infection and development of these tumors. In the present study, we have examined DC generated from blood adherent cells from 8 Swedish MM patients at different clinical stages and 2 patients with monoclonal gammopathy of undetermined significance. In addition, 6 myeloma cell lines and bone marrow cells from 2 MM patients were also studied. By polymerase chain reaction (PCR), including nested PCR, no virus DNA was demonstrable in the patients' DC or in myeloma cell lines or fresh bone marrow cells. Moreover, no antibody against KSHV was found in the serum of these 10 patients. Thus, our results indicate that blood-derived DC of MM patients in Sweden usually are not infected with KSHV/HHV-8. This study also suggests that KSHV/HHV-8 is not regularly associated with MM and consequently does not play a primary role in the pathogenesis of these tumors.

Excess body fat, obesity, is one of the most common disorders in clinical practice. Obese individuals are at increased risk for physical ailments, such as type 2 diabetes, coronary heart disease, hypertension, and several types of cancer. The location of the body fat is a major determinant of the degree of excess morbidity and mortality due to obesity. More specifically, the amount of subcutaneous truncal or abdominal fat, and the amount of visceral fat located in the abdominal cavity independently predicts obesity-related adverse health outcomes. The obesity gene map shows putative loci on all chromosomes except Y. More than 300 genes, markers, and chromosomal regions have been associated or linked with human obesity phenotypes. These genes can be divided into two broad categories: (a) rare gene variants that have a strong influence, and (b) common gene variants that have a weaker influence on obesity phenotypes. Studies in humans have suggested a positive association between obesity, hypertension, and insulin resistance, with alleles at the glucocorticoid receptor gene. In this article, we will estimate the risk by which such gene polymorphism mediates a role in obesity.

Previous research has indicated that phobic anxiety is associated with coronary heart disease. In this study, the possible association between social anxiety and various anthropometric, metabolic, and endocrine measurements known to be associated with cardiovascular disease were studied in a population-based cohort of 216 women 41-42 years old. Each participant was assessed by means of a DSM-IV based self-report questionnaire regarding social anxiety and related psychiatric diagnoses. Waist-to-hip ratio (WHR), body mass index (BMI), and serum levels of lipids and hormones were assessed. The prevalence of social anxiety was 14% (n=31). The social anxiety group displayed higher serum levels of triglycerides (1.3+/-0.9 vs. 1.0+/-0.5, P=0.003) and low-density lipoprotein (LDL) (3.3+/-0.8 vs. 3.0+/-0.7, P=0.03), but lower high-density lipoprotein (HDL) (1.4+/-0.3 vs. 1.6+/-0.4, P=0.04) and HDL/LDL ratio (0.46+/-0.15 vs. 0.57+/-0.22, P=0.008) than the other women. Serum levels of total testosterone (1.6+/-0.8 vs. 2.2+/-1.1, P=0.013) and free thyroxin (14+/-2 vs. 16+/-4, P=0.04) were lower in subjects confirming social anxiety. While WHR was significantly higher in the social anxiety group (0.83+/-0.06 vs. 0.80+/-0.07, P=0.016), BMI did not differ between the groups. Our data suggest that self-reported social anxiety is associated with two established risk factors for cardiovascular disease: dyslipidemia and increased WHR.

Estrogens are known to play a key role in the regulation of various aspects of behavior. In order to study the potential contribution of genetic variation in the estrogen receptor (ER) alpha to specific personality traits, we investigated a repeat polymorphism in the ER alpha gene in 172 42-year-old women who had been assessed using the Karolinska Scales of Personality (KSP). Based on the hypothesis that there is a relationship between the length of a repeat polymorphism and gene function,(1) the alleles were divided into two groups: short and long. In order to elucidate the possible influence of the ER alpha gene on the different aspects of personality measured by means of the KSP, the possible association between this gene and four different factors ('neuroticism', 'psychoticism', 'non-conformity', and 'extraversion') was analysed. 'Neuroticism', 'psychoticism', and 'non-conformity' all appeared to be associated with the ER alpha gene. After correction for multiple comparisons by means of permutation analysis, the associations with the factor 'non-conformity'--including the subscales 'indirect aggression' and 'irritability'--and the factor 'psychoticism'--including the subscale 'suspicion'--remained significant. The results suggest that the studied dinucleotide repeat polymorphism of the ER alpha gene may contribute to specific components of personality.

Depression is associated with an increased risk of developing cardiovascular disease and type 2 diabetes mellitus. Abdominal obesity is also a high risk factor for these diseases. Therefore, symptoms of depression and anxiety were examined in relation to abdominal obesity. A total of 59 middle-aged men volunteered for measurements with the Hamilton Depression Scale (HDS), the Montgomery–Asberg Depression Rating Scale (MADRS), the Beck Depression Inventory (BDI) and the Hamilton Anxiety Scale (HAS). These results were examined in relation to body mass index (BMI), waist/hip ratio (WHR) and sagittal abdominal diameter, a measurement of intra-abdominal fat mass, and metabolic variables. Men with WHR>1.0 ( n =26) in comparison with men with normal WHR ( n =33) showed significantly higher sum scores in all the scales used. There were positive correlations between the sum scores of all the depression scales and the WHR or the sagittal abdominal diameter. BMI correlated comparatively weakly only with the HDS. The correlations with the WHR remained when the influence of BMI was eliminated, suggesting that obesity is less involved than centralization of body fat. Insulin and glucose were significantly related to the HDS. Morning cortisol levels were negatively related to the BDI and (borderline) to the MADRS, suggesting perturbations of the regulation of the hypothalamic–pituitary–adrenal axis. We conclude that men with abdominal obesity have symptoms of depression and anxiety.

Androgens are suggested to interact with leptin production and with insulin sensitivity in both polycystic ovary syndrome (PCOS) and obesity. The aim of the study was to follow these interactions along with two forms of antiandrogen treatment. Twenty women with PCOS were treated with ethinylestradiol and high dose of cyproteroneacetate (EE-CA) and 8 with the gonadotrophin-releasing hormone (GnRH) analogue goserelin for 6 months. The patients were divided into a low and a high body weight group and compared with a group of overweight women without PCOS. Both treatments resulted in a significant reduction of free testosterone but the concentration of leptin remained unchanged. EECA treatment resulted in deterioration and GnRH in improvement of insulin sensitivity. Serum leptin correlated only with body weight and body fat. It is concluded that leptin levels do not adequately reflect changes in insulin sensitivity or androgen levels after short-term antiandrogen or antigonadotropin treatment.

Little is known about the metabolic or cardiovascular effects of selective ER modulators (SERMs), such as raloxifene hydrochloride (RLX), in postmenopausal women with type 2 diabetes mellitus (DM). Therefore, the effect of RLX vs. placebo (PL) on glycemic control, insulin sensitivity, as well as effects on a number of hormone, lipid, coagulation, and safety factors were determined in 30 postmenopausal women with type 2 DM in a randomized, double blind, cross-over trial. All participants had a SHBG serum concentration below 60 nmol/liter at baseline and had stable diabetes controlled by either oral hypoglycemic agents or diet for 1 month. In the first treatment period, participants received 12 wk of either PL or RLX, followed by an 8-wk washout before the second treatment period. In the second treatment period, participants were crossed over to the other treatment. Compared with PL, RLX did not significantly affect fasting blood glucose, hemoglobin A(1c), lipids, fasting insulin, or insulin sensitivity (as measured by the euglycemic clamp technique). Compared with PL, RLX reduced fibrinogen levels by 0.77 g/liter (P0.001), IGF-I by 2.4 nmol/liter (P0.001), and free T by 0.73 pmol/liter (P = 0.038) and increased SHBG by 5.5 nmol/liter (P = 0.001) and IGF-binding protein-3 by 0.57 ng/ml (P = 0.007). Our results demonstrate that RLX does not significantly affect glycemic control and has favorable or neutral effects on selected surrogate markers of cardiovascular risk in postmenopausal women with type 2 diabetes mellitus while decreasing hyperandrogenicity in these patients.

Ljung T, Ahlberg A-C, Holm G, Friberg P, Andersson B, Eriksson E, Bjorntorp P (Sahlgrenska University Hospital and University of Goteborg, Goteborg, Sweden). Treatment of abdominally obese men with a serotonin reuptake inhibitor: a pilot study. J Intern Med 2001; 250: 219–224. Objective. To investigate the effects of a selective serotonin reuptake inhibitor (SSRI) on the neuroendocrine and autonomic nervous system perturbations found in abdominal obesity. Design. Treatment for 6 months with citalopram and for 6 months with placebo using a double-blind, cross-over design, with a 2-month wash-out period between treatment periods. Subjects. Sixteen healthy men, 45–60 years, moderately obese and with an abdominal fat distribution. Measurements. Anthropometry, three different depression rating scales, serum lipids, testosterone, IGF-I, oral glucose tolerance test (OGTT), pituitary stimulation with corticotropin releasing hormone (CRH), arithmetic stress test, and excretion of cortisol and metoxycatecholamines in urine, collected during 24 h. Results. Cortisol concentrations in the morning were low before treatment, indicating a perturbed function of the hypothalamic-pituitary-adrenal (HPA) axis. After treatment with citalopram morning cortisol concentrations rose to normal. Cortisol concentrations after stimulation with CRH or stress were elevated by citalopram treatment, but urinary cortisol excretion was unchanged. The glucose concentrations after OGTT (120 min) tended to be reduced, with unchanged insulin concentrations, whilst other metabolic values did not change during treatment. Heart rate after administration of CRH, and during laboratory stress test, decreased by treatment with citalopram. Diurnal urinary excretion of metoxycatecholamines tended to decrease. Neither body mass index nor waist/hip circumference ratio decreased. Depression scores were within normal limits before treatment and did not change. Conclusion. The results of this pilot study indicate improvements in the regulation of neuroendocrine-autonomic systems as well as metabolism in abdominal obesity during treatment with an SSRI.

Activation of telomerase is essential for in vitro cellular immortalization and tumorigenesis. In the present study, we investigated telomerase activation and its implications in plasma cell dyscrasias including monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM) and plasma cell leukaemia (PCL). All 5 patients with MGUS exhibited normal levels of telomerase activity in their plasma cells. Elevated telomerase activity was found in the samples from 21/27 patients with MM and 4/4 with PCL. In addition, 4 myeloma cell lines all expressed high levels of telomerase activity. The expression of telomerase reverse transcriptase (hTERT) and telomerase RNA template (hTER) was positively associated with the levels of telomerase activity in MM/PCL. Tankyrase expression was upregulated, concomitant with the induction of hTERT and activation of telomerase in MM/PCL. The present findings indicate that MGUS cells may not be immortalized and that activation of telomerase plays a role in the malignant transformation from MGUS to MM. © 2001 Cancer Research Campaign http://www.bjcancer.com