Psychological aspects of endocrine disease.

This review illustrates how an innovative psychoneuroendocrine approach to endocrine patients may improve their management. Important psychological issues pertain to all the different phases of an endocrine disorder. Before disease onset, stressful life events may play a pathogenetic role and, together with chronic stress, may contribute to a cumulative burden also called allostatic load; psychological and psychiatric symptoms are common both in the prodromal and in the active phase of illness; after cure or remission, there could be residual symptoms and impaired quality of life that deserve attention. All these aspects should be taken into consideration and introduced in current endocrine care and practice.

Demoralization: a systematic review on its clinical characterization.

BACKGROUND: Demoralization has been described as a psychological state characterized by helplessness, hopelessness, a sense of failure and the inability to cope. METHODS: We conducted a systematic review with qualitative data analysis following PRISMA criteria with the following aims: to review validated assessment instruments of the demoralization syndrome, report main findings regarding demoralization as measured by validated instruments that emerge in the literature, compare and report evidence for the clinical utility of the identified instruments. Utilizing the key word 'demoralization' in PubMed and PsycINFO databases, an electronic search was performed, supplemented by Web of Science and manual searches. Study selection criteria included the assessment of medical patients and use of instruments validated to assess demoralization. Seventy-four studies were selected. RESULTS: Four instruments emerged in the literature. Main findings concern prevalence rates of demoralization, evidence of discriminant validity from major depression, factors associated with demoralization and evidence of clinical utility. The instruments vary in their definition, the populations they aim to assess, prevalence rates they estimate and their ability to discriminate between different conditions. Nonetheless, demoralization appears to be a distinctive psychological state characterized by helplessness, hopelessness, giving up and subjective incompetence. It is not limited to life-threatening diseases such as cancer, but may occur in any type of clinical situation. It is associated with stress and adverse health outcomes. CONCLUSIONS: Studies addressing the incremental value of demoralization in psychiatry and psychology are needed. However, demoralization appears to entail specific clinical features and may be a distinct condition from major depression.

KRAS and BRAF mutations and MSI status in precursor lesions of colorectal cancer detected by colonoscopy.

Colorectal cancer (CRC) is one of the most frequent cancers worldwide. Adenoma is the main precursor lesion and, recently, the serrated polyps were described as a group of colorectal lesions with malignant potential. The morphologic and biologic characterizations of serrated polyps remain limited. The aim of the present study was to determine the frequency of KRAS and BRAF mutations and microsatellite instability (MSI) in CRC precursor lesions, to evaluate the association between molecular, pathologic and morphologic alterations in precursor lesions and to compare with the alterations detected in CRC. A series of 342 precursor lesions were removed from 155 patients during colonoscopy. After morphologic classification, molecular analysis was performed in 103 precursor lesions, and their genetic profile compared with 47 sporadic CRCs. Adenomas were the main precursor lesions (70.2%). Among the serrated polyps, the main precursor lesion was hyperplastic polyps (HPs) (82.4%), followed by sessile serrated adenomas (12.7%) and traditional serrated adenomas (2.0%). KRAS mutations were detected in 13.6% of the precursor lesions, namely in adenomas and in HPs, but in no serrated adenoma. BRAF mutations were found in 9 (8.7%) precursor lesions, mainly associated with serrated polyps and absent in adenomas (P<0.001). High MSI (MSI-H) was absent in precursor lesions. In the 47 CCR cases, 46.8% exhibited KRAS mutation, 6.5% BRAF mutations and 10.6% MSI-H. This study confirms the role of KRAS and BRAF mutations in CRC carcinogenesis, a crucial step in implementing CRC screening strategies.

Type A behaviour: a reappraisal of its characteristics in cardiovascular disease.

AIMS: The role of type A behaviour in cardiovascular disease is controversial and most of the research is based on self-rating scales. The aim of this study was to assess the prevalence of type A behaviour in cardiology and in other medical settings using reliable interview methods that reflect its original description. METHODS: A sample of 1398 consecutive medical patients (198 with heart transplantation, 153 with a myocardial infarction, 190 with functional gastrointestinal disorders, 104 with cancer, 545 with skin disorders and 208 referred for psychiatric consultation) was administered the Structured Clinical Interview for the DSM-IV and the Structured Interview for the Diagnostic Criteria for Psychosomatic Research (DCPR) which identifies 12 clusters, including type A behaviour. RESULTS: A cardiac condition was present in 366 patients. There was a significant difference in the prevalence of type A behaviour in cardiovascular disease (36.1%) compared with other medical disorders (10.8%). Type A behaviour frequently occurred together with psychiatric and psychosomatic disturbances, particularly irritable mood, even though in the majority of cases it was not associated with DSM-IV diagnoses. Among cardiac patients, those with type A behaviour were less depressed, demoralised and worried about their illness. CONCLUSIONS: Type A behaviour was found to occur in about a third of cases of patients with cardiovascular disease. Only in a limited number of cases was it associated with depression. It has a lifestyle connotation that may have important clinical consequences as to stress vulnerability and illness behaviour.

Molecular pathogenesis of cholangiocarcinoma.

Epidemiological data from the last years show an increasing trend of incidence and mortality of cholangiocarcinoma (CC) worldwide. Many pathophysiologic aspects of this neoplasia are still unknown and need to be fully discovered. However, several progresses were recently made in order to establish the molecular mechanisms involved in the transformation and growth of malignant cholangiocytes. The principal concept that at least seems to be established is that cholangiocarcinogenesis is a multistep cellular process evolving from a normal condition of the epithelial biliary cells through a chronic inflammation status ending with malignant transformation. The bad prognosis related to CC justifies why a better identification of the molecular mechanisms involved in the growth and progression of this cancer is required for the development of effective preventive measures and valid treatment regimens. This Paper describes the scientific progresses made in the last years in defining the molecular pathways implicated in the generation of this devastating disease.

Clinimetrics: the science of clinical measurements.

'Clinimetrics' is the term introduced by Alvan R. Feinstein in the early 1980s to indicate a domain concerned with indexes, rating scales and other expressions that are used to describe or measure symptoms, physical signs and other clinical phenomena. Clinimetrics has a set of rules that govern the structure of indexes, the choice of component variables, the evaluation of consistency, validity and responsiveness. This review illustrates how clinimetrics may help expanding the narrow range of information that is currently used in clinical science. It will focus on characteristics and types of clinimetric indexes and their current use. The clinimetric perspective provides an intellectual home for clinical judgment, whose implementation is likely to improve outcomes both in clinical research and practice.

A cluster analysis-derived classification of psychological distress and illness behavior in the medically ill.

BACKGROUND: The classification of psychological distress and illness behavior in the setting of medical disease is still controversial. Current psychiatric nosology does not seem to cover the spectrum of disturbances. The aim of this investigation was to assess whether the joint use of DSM-IV categories and the Diagnostic Criteria for Psychosomatic Research (DCPR), that provide identification of syndromes related to somatization, abnormal illness behavior, irritable mood, type A behavior, demoralization and alexithymia, could yield subtyping of psychosocial variables in the medically ill. METHOD: A cross-sectional assessment using both DSM-IV and the DCPR was conducted in eight medical centers in the Italian Health System. Data were submitted to cluster analysis. Participants were consecutive medical out-patients and in-patients for whom a psychiatric consultation was requested. A total of 1700 subjects met eligibility criteria and 1560 agreed to participate. RESULTS: Three clusters were identified: non-specific psychological distress, irritability and affective disturbances with somatization. CONCLUSIONS: Two-step cluster analysis revealed clusters that were found to occur across clinical settings. The findings indicate the need of expanding clinical assessment in the medically ill to include the various manifestations of somatization, illness behavior and subclinical distress encompassed by the DCPR.

Efficacy of the sequential integration of psychotherapy and pharmacotherapy in major depressive disorder: a preliminary meta-analysis.

BACKGROUND: Prevention of relapse and recurrence represents an important task in the successful treatment of major depressive disorder (MDD). The aim of this meta-analysis was to examine the efficacy of the sequential integration of psychotherapy and pharmacotherapy in reducing the risk of relapse and recurrence in MDD. METHOD: Keyword searches were conducted in Medline, EMBASE, PsycINFO and the Cochrane Library from inception of each database to December 2008. Randomized controlled trials examining the efficacy of the administration of psychotherapy after successful response to acute-phase pharmacotherapy in the treatment of adults with MDD were considered for inclusion in the meta-analysis. RESULTS: Eight high-quality studies with 442 patients in a sequential treatment arm and 433 in a control treatment arm were included. The pooled risk ratio (RR) for relapse/recurrence was 0.797 [95% confidence interval (CI) 0.659-0.964] according to the random-effects model, suggesting a relative advantage in preventing relapse/recurrence for the sequential administration of treatments compared with control conditions. Performing subgroup analyses, we found a trend favoring psychotherapy during continuation of antidepressant drugs compared to antidepressants or treatment as usual (RR 0.842, 95% CI 0.674-1.051). Patients randomized to psychotherapy while antidepressants were discontinued were significantly less likely to experience relapse/recurrence compared to controls (RR 0.650, 95% CI 0.463-0.912). CONCLUSIONS: We found evidence that the sequential integration of psychotherapy and pharmacotherapy is a viable strategy for preventing relapse and recurrence in MDD. In addition, our findings suggest that discontinuation of antidepressant drugs may be feasible when psychotherapy is provided.

New clinical strategies of assessment of comorbidity associated with substance use disorders.

The introduction of "dual diagnosis" had the merit of drawing attention on substance use among patients with mental illness. In due course, as what often happens with innovations, the concept of dual diagnosis displayed considerable limitations and was progressively replaced by comorbidity. This paper critically reviews the limitations of dual diagnosis and comorbidity and formulates an alternative proposal based on clinimetric methods. In many instances of diagnostic reasoning in psychiatry and in clinical psychology, the process ends with the identification of the disorders and their diagnoses. However, diagnostic end-points, the customary guidance of diagnostic reasoning, should be replaced by the conceptualization of disorders as "transfer stations," which are amenable to longitudinal verification and modification. Indeed, diagnoses might encompass a wide range of manifestations, seriousness, prognosis, and response to treatment that need to be evaluated. A new clinimetric approach which takes advantage of clinimetric methods (including macro-analysis, micro-analysis, staging, and evaluation of subclinical symptoms) is proposed. This approach may allow an accurate analysis of the different problem areas of each patient and their hierarchical organization and may yield important implications for mental health and substance abuse clinics.

Psychosomatic renewal of health care.

Psychosomatic medicine may be defined as a comprehensive, interdisciplinary framework for: assessment of psychological factors affecting individual vulnerability as well as course and outcome of illness; biopsychosocial consideration of patient care in clinical practice; specialist interventions to integrate psychological therapies in the prevention, treatment and rehabilitation of medical disease. Current advances in the field have practical implications for medical research and practice, with particular reference to the role of lifestyle, the challenge of medically unexplained symptoms, the psychosocial needs entailed by chronic illness, the appraisal of therapy beyond pharmaceutical reductionism, and the function of the patient as a health producer. Today the field of psychosomatic medicine is scientifically rigorous, more diversified and therapeutically relevant than ever before.

Psychosomatic medicine.

Psychosomatic medicine may be defined as a comprehensive, interdisciplinary framework for: assessment of psychological factors affecting individual vulnerability as well as course and outcome of illness; biopsychosocial consideration of patient care in clinical practice; specialist interventions to integrate psychological therapies in the prevention, treatment and rehabilitation of medical disease. The aim of this review was to provide an updated definition of psychosomatic medicine, to outline its boundaries with related disciplines and to illustrate its main contributions to clinical and preventive medicine. A review of the psychosomatic literature, using both Medline and manual searches, with particular reference to articles, which could be relevant to clinical practice, was performed. Current advances in the field have practical implications for medical research and practice, with particular reference to the role of lifestyle, the challenge of medically unexplained symptoms, the psychosocial needs entailed by chronic illness, the appraisal of therapy beyond pharmaceutical reductionism, the function of the patient actively contributing to his/her health. Today, the field of psychosomatic medicine is scientifically rigorous, more diversified and therapeutically relevant than ever before.

Assessment of airborne soy-hull allergen (Gly m 1) in the Port of Ancona, Italy.

BACKGROUND: Epidemic asthma outbreaks are potentially a very high-risk medical situation in seaport towns where large volumes of soybean are loaded and unloaded Airborne allergen assessment plays a pivotal role in evaluating the resulting environmental pollution. OBJECTIVE: The aim of this study was to measure the airborne Gly m 1 allergen level in the seaport of Ancona in order assess the soybean-specific allergenic risk for the city. METHODS: Allergen and PM10 were evaluated at progressive distances from the port area. Allergen analysis was performed by monoclonal antibody-based immunoassay on the sampled filters. Daily meteorological data were obtained from the local meteorological station. For estimating the assimilative capacity of the atmosphere, an approach based on dispersive ventilation coefficient was tried. RESULTS: The allergen concentrations detected were low (range = 0.4-171 ng/m3). A decreasing gradient of the airborne allergen from the unloading area (22.1 +/- 41.2 ng/m3) to the control area (0.6 +/- 0.7 ng/m3) was detected. The concentration of the airborne Gly m 1 was not coupled with the presence of the soy-carrying ships in the port. A statistically significant relationship between airborne allergen, PM10 and local meteorological parameters quantifies the association with the atmospheric condition. CONCLUSION: Airborne Gly m 1 is part of the atmospheric dust of Ancona. The low level of this allergen seems consistent with the absence of asthma epidemic outbreak.

Completely isolated enteric duplications cysts: a survey of four cases.

Enteric duplication cysts are uncommon congenital abnormalities with epithelial lining. They are cystic or tubular structures intimately attached to a portion of the gastrointestinal tract; they are usually located on the mesenteric site of the digestive tract sharing common blood supply. Isolated cystic duplications are an extremely rare variant with their own blood supply: in literature only five cases have been reported. We present our four cases series of this uncommon anomaly.

Exendin-4, a glucagon-like peptide 1 receptor agonist, protects cholangiocytes from apoptosis.

BACKGROUND AND AIMS: Progression of chronic cholestatic disorders towards ductopenia results from the dysregulation of cholangiocyte survival, with cell death by apoptosis prevailing over compensatory proliferation. Currently, no therapy is available to sustain cholangiocyte survival in the course of those disorders. It was recently shown that cholangiocytes express the glucagon-like peptide-1 receptor (GLP-1R); its activation results in enhanced proliferative reaction to cholestasis. The GLP-1R selective agonist exendin-4 sustains pancreatic beta cell proliferation and prevents cell death by apoptosis. Exendin-4 is now employed in humans as a novel therapy for diabetes. The aim of the present study was to verify whether exendin-4 is effective in preventing cholangiocyte apoptosis. METHODS: In vitro, tests were carried out to determine if exendin-4 is able to prevent apoptosis of cholangiocytes isolated from normal rats induced by glycochenodeoxycholic acid (GCDCA); in vivo, animals subjected to 1 week of bile duct ligation and to a single intraperitoneal injection of CCl(4) were treated with exendin-4 for 3 days. RESULTS: Exendin-4 prevented GCDCA-induced Bax mitochondrial translocation, cytochrome c release and an increase in caspase 3 activity. Phosphatidylinositol 3-kinase, but not cAMP/protein kinase A or Ca(2+)/calmodulin-dependent protein kinase inhibitors, neutralised the effects of exendin-4. In vivo, exendin-4 administration prevented the increase in TUNEL (terminal deoxynucleotidyl transferase-mediated triphosphate end-labelling)-positive cholangiocytes and the loss of bile ducts observed in bile duct-ligated rats treated with CCl(4). CONCLUSION: Exendin-4 prevents cholangiocyte apoptosis both in vitro and in vivo; such an effect is due to the ability of exendin-4 to counteract the activation of the mitochondrial pathway of apoptosis. These findings support the hypothesis that exendin-4 may be effective in slowing down the progression of cholangiopathies to ductopenia.

Human cholangiocarcinoma development is associated with dysregulation of opioidergic modulation of cholangiocyte growth.

BACKGROUND/AIMS: Incidence of cholangiocarcinoma is increasing worldwide, yet remaining highly aggressive and with poor prognosis. The mechanisms that drive cholangiocyte transition towards malignant phenotype are obscure. Cholangiocyte benign proliferation is subjected to a self-limiting mechanism based on the autocrine release of endogenous opioid peptides. Despite the presence of both, ligands interact with delta opioid receptor (OR), but not with microOR, with the consequent inhibition of cell growth. We aimed to verify whether cholangiocarcinoma growth is associated with failure of opioidergic regulation of growth control. METHODS: We evaluated the effects of OR selective agonists on cholangiocarcinoma cell proliferation, migration and apoptosis. Intracellular signals were also characterised. RESULTS: Activation of microOR, but not deltaOR, increases cholangiocarcinoma cell growth. Such an effect is mediated by ERK1/2, PI3K and Ca(2+)-CamKIIalpha cascades, but not by cAMP/PKA and PKCalpha. microOR activation also enhances cholangiocarcinoma cell migration and reduces death by apoptosis. The anti-apoptotic effect of microOR was PI3K dependent. CONCLUSIONS: Our data indicate that cholangiocarcinoma growth is associated with altered opioidergic regulation of cholangiocyte biology, thus opening new scenarios for future surveillance or early diagnostic strategies for cholangiocarcinoma.

Sequential treatment of depression in primary care.

BACKGROUND: In the past decade, in clinical psychiatry several investigations suggested the usefulness of a sequential way of integrating pharmacotherapy and psychotherapy in mood disorders. The aim of this paper was to illustrate the practical implications of sequential treatment strategy for depression in primary care, with particular reference to the increasingly common problem of recurrent depression. METHODS: The Authors tried to integrate the evidence which derives from meta-analyses and comprehensive general reviews with the insights which derive from controlled studies concerned with specific populations. CONCLUSIONS: The sequential treatment of mood disorders is an intensive, two-stage approach, which derives from the awareness that one course of treatment with a specific tool (whether pharmacotherapy or psychotherapy) is unlikely to entail solution to the affective disturbances of patients, both in research and in clinical practice settings. The aim of the sequential approach is to add therapeutic ingredients as long as they are needed. In this sense, it introduces a conceptual shift in clinical practice.

[Well-being therapy]. / Wohlbefindenstherapie sorgt für zufriedene Patienten. "Ich bin chronisch krank-- aber es geht mir gut"

Well-being and quality of life are leading psychological factors that are basically independent of disease and the burdens of life. The more problems a person has to cope with, the more important they become as factors impacting upon an illness. Well-being Therapy (WBT) is a novel psychotherapeutic strategy aimed at promoting psychological well-being. WBT is based on Ryff's multidimensional model of subjective well-being which comprises six subdivisions: mastery of the environment, personal growth, purpose and meaning of life, autonomy, self-acceptance and positive relationships. The aim of this therapy is to improve the patient's performance/activities in all of these areas.

Leaching and mechanical behaviour of concrete manufactured with recycled aggregates.

The reuse of debris from building demolition is of increasing public interest because it decreases the volume of material to be disposed to landfill. This research is focused on the evaluation of the possibility of reusing recycled aggregate from construction or demolition waste (C&D) as a substitute for natural aggregate in concrete production. In most applications, cement based materials are used for building construction due to their cost effectiveness and performance; however their impact on the surrounding environment should be monitored. The interstitial pore fluid in contact with hydrated cementitious materials is characterized by persistent alkaline pH values buffered by the presence of hydrate calcium silicate, portlandite and alkaline ions. An experimental plan was carried out to investigate concrete structural properties in relation to alkali release in aqueous solution. Results indicate that the presence of recycled aggregate increases the leachability of unreactive ions (Na, K, Cl), while for calcium the substitution resulted in a lower net leaching. In spite of the lower mechanical resistance (40% less), such a waste concrete may be suggested as more environmentally sustainable.