Monthly variation in prevalence rates of comorbid depression and anxiety in the general population at 63-65 degrees North: the HUNT study

BACKGROUND: To investigate monthly variation in depression, anxiety and their comorbidity (COM) in an epidemiologic study and their association to monthly variation in suicide rates. METHODS: 60,995 participants of the Health Study of Nord-Tr?ndelag County in 1995-97 rated themselves on the Hospital Anxiety and Depression Scale (HADS) in all months except July. All 10,670 male and 3833 female suicides in Norway from 1969 through 1996 were included. RESULTS: The prevalence of comorbid anxiety and depression was highest in spring (April, May) and in October (p<0.01). There was a correlation between the monthly variation in the national suicide rate and monthly variation in comorbid anxiety and depression (r=0.72, df=11, p=0.01) and for male alone (r=0.67, df=11, p=0.03). There was also a significant monthly variation in the prevalence of depression (p<0.001) and no monthly variation in the prevalence of anxiety. LIMITATIONS: Limited information about the third of the population who did not take part in the HUNT-2 Study. HADS based depression and anxiety cover psychological symptoms, not somatic and social ones. In relation to DSM-IV and ICD-10 defined anxiety disorders and depressions, the sensitivity and specificity of HADS caseness, give a considerable number of false-positive cases. CONCLUSIONS: Increased prevalence of comorbid depression and anxiety in males during spring, and its association with suicidality should have clinical importance, as identification and treatment could influence suicide rates.     

Radioimmunoassay for autoantibodies against interferon omega; its use in the diagnosis of autoimmune polyendocrine syndrome type I

Patients with the autoimmune polyendocrine syndrome I (APS I) have high titers of neutralizing IgG autoantibodies against type I interferons (IFNs), in particular IFN-omega. Until now, the most specific assay has been the antiviral interferon neutralizing assay (AVINA), which has the drawbacks of requiring a cytolytic virus, being cumbersome and difficult to standardise. We have developed a fast and reliable immunoassay based on radiolabelled IFN-omega for quantifying anti-IFN-omega antibodies. Sera from 48 APS I patients were analysed together with those from 5 control groups. All sera from APS I patients were positive for anti-IFN-omega, while, except one serum, all sera from the controls were negative. This method has the advantage over bioassays that it is readily adapted to high throughput. It provides an alternative, sensitive and specific diagnostic test for APS I, and an ideal screening tool to precede mutational analyses of the AIRE gene in suspected APS I cases.     

Aminoglutethimide enzyme induction: pharmacological and endocrinological implications

Summary Aminoglutethimide is an aromatase inhibitor that is successfully used for endocrine treatment of advanced breast cancer. This drug also stimulates the activity of hepatic mixed-function oxidases, increasing the metabolism of several drugs, including warfarin, digitoxin, antipyrine and theophylline. It also increases the plasma clearance rate of oestrone sulphate. As this oestrogen may be an important substrate for tumour cells, stimulation of oestrone sulphate metabolism may be a component of the mechanism of action of aminoglutethimide.     

Longchain serum fatty acids and risk of thyroid cancer: A population-based case-control study in Norway

Epidemiologic studies have shown an association between seafood consumption and risk of thyroid cancer. Fish meals increase the serum concentrations of the longchain fatty acids, eicosapentaenoic acid (205,n-3) (EPA) and docosahexaenoic acid (226,n-3) (DHA), for days. The hypothesis that serum concentrations of fatty acids may be associated with thyroid cancer risk therefore was tested in a population-based case-control study with 74 cases and 221 matched controls. Seventy-three cases with sera in the Norwegian serum bank (JANUS) were identified in the Norwegian Cancer Registry and matched with three controls, also in JANUS, on age, gender, place of residence, and time of blood sampling. Each case was matched with two controls. Serum concentrations of 11 longchain fatty acids were determined blindly by gas chromatography for all subjects. Controls were divided into three groups with increasing serum fatty acid concentrations, and odds ratios between cases and controls were estimated relative to the group with lowest serum level by univariate and multivariate analyses. The main finding was a significant inverse relation between the sum of arachidonic acid (204,n-6) (AA) and DHA serum concentrations and thyroid cancer risk. The significance of this association was weakened when the analyses were restricted to the papillary type of thyroid carcinoma. It was of the same order of magnitude whether the period between blood sampling and diagnosis was greater than eight years, or eight or less years. High EPA/AA ratio, indicating consumption of fish fat, was not associated significantly with increased thyroid-cancer risk. These data indicate that the association between seafood ingestion and increased thyroid-cancer risk may not be caused by the marine fatty acids.     

Development of aromatase inhibitors and their pharmacologic profile

Major advances have been recently made in the treatment of postmenopausal women with hormone-sensitive breast cancer. It is widely accepted that estrogen is associated with the progression of hormone-sensitive breast cancer. Whereas previous therapy was based on surgical ablation (ovariectomy, adrenalectomy, and hypophysectomy) or additive treatment (estrogens, androgens), more recently antiestrogens (in premenopausal as well as postmenopausal women), medical ovarian ablation, and aromatase inhibition have replaced these procedures. The current focus of clinical research efforts is to maximize efficacy with these agents and determine an effective treatment strategy for these patients. This article reviews the development of aromatase inhibitors and inactivators (AIs), with particular emphasis on the potent third-generation agents now available. Also provided is information on the relative potency and efficiency of estrogen synthesis inhibition with these agents. Results from in vitro and in vivo studies of AIs suggest that there is variability in efficacy among agents in this class, and the potential clinical implications of these variations are discussed.     

Proteomics approaches to elucidate oncogenic tyrosine kinase signaling in myeloid malignancies

Myeloid malignancies frequently harbor specific mutations in protein tyrosine kinases leading to oncogenic cell signaling. The most extensively investigated example is chronic myeloid leukemia, where the pathogenic tyrosine kinase fusion protein Bcr-Abl is a successful target for disease control by the specific inhibitor imatinib mesylate. In acute myeloid leukemia the receptor tyrosine kinase Flt3 is frequently mutated and inhibitors to impair the oncogenic signaling are in development. In this review we exemplify oncogenic signaling and how signal pathways can be unraveled with help from proteomics-based technologies. The distinction between cell extract and single cell approaches aiming at rigorous standardization and reliable quantitative aspects for future proteomics-based diagnostics is discussed.     

Antitumor efficacy improved by local delivery of species-specific endostatin

OBJECT: Conflicting results have been reported concerning the antitumor efficacy of the angiogenesis inhibitor endostatin. This may be due to differences in the biological distribution of endostatin between studies or to the varying biological efficacies of the different protein forms that were examined. To address this issue, the authors used a local delivery approach in which each tumor cell secreted endostatin, providing uniform endostatin levels throughout the tumors. This allowed a direct assessment of the biological efficacy of soluble endostatin in vivo. METHODS: The authors genetically engineered BT4C gliosarcoma cells so that they would stably express and secrete either the human or murine form of endostatin. Endostatin-producing cells or mock-infected cells were implanted intracerebrally in syngeneic BD-IX rats. The antitumor efficacy of endostatin was evaluated on the basis of survival data and tumor volume comparisons. In addition, microvascular parameters were assessed. The authors confirmed the continuous release of endostatin by the BT4C cells. A magnetic resonance imaging-assisted comparison of tumor volumes revealed that local production of murine endostatin significantly inhibited tumor growth. Notably, 40% of the animals in this treatment group experienced long-term survival without histologically verifiable tumors 7 months after cell implantation. After local treatment with murine endostatin, tumor blood plasma volumes were reduced by 71%, microvessel density counts by 84%, and vascular area fractions by 75%. In contrast, human endostatin did not inhibit tumor growth significantly in this model. Centrally located regions of necrosis were present in tumors secreting both the human and the murine species-specific form of endostatin. CONCLUSIONS: The results suggest that endostatin inhibits tumor angiogenesis in vivo in a species-specific manner.     

Genomics-based prognosis and therapeutic prediction in breast cancer

Breast cancer is a heterogeneous disease. DNA microarray technology is being applied to breast cancer to identify new prognostic biomarkers, to predict response to therapy, and to discover targets for the development of novel therapies. New diagnostic assays based on global gene expression are being introduced into clinical practice or tested in large-scale clinical trials. This review focuses on translational studies using microarray analyses and discusses best practice features and pitfalls. We note that factors that predict metastatic disease are not necessarily the same factors that predict therapeutic response. We believe that the characterization and discernment of different systems among breast cancers is crucial for understanding drug sensitivity and resistance mechanisms and for guiding therapy.