Family history validation of a definition of mixed depression

PURPOSE: The study aim was to test different definitions of mixed depression, defined as a depression with concurrent hypomanic symptoms. METHODS: Consecutive 245 non-tertiary care outpatients with bipolar II disorder (BP-II) and 189 non-tertiary care outpatients with major depressive disorder (MDD) were interviewed (off psychoactive drugs) using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders-Clinician Version, Hypomania Interview Guide (HIG), and Family History Screen when presenting for major depressive episode (MDE) treatment. Intra-MDE hypomanic symptoms were systematically assessed. Mixed depression was defined as an MDE with concurrent hypomanic symptoms. Receiver operating characteristic (ROC) analysis and multivariate analysis were used to test different definitions of mixed depression (dimensional and categorical ones). Factor analysis was also used. Bipolar family history was the validator. FINDINGS: Bipolar II disorder, vs MDD, had significantly more intra-MDE hypomanic symptoms (racing/crowded thoughts, irritable mood, psychomotor agitation, more talkativeness, and increased goal-directed and risky activities). Major depressive episode plus 3 or more hypomanic symptoms was present in 68.7% of BP-II and 42.3% of MDD. A "motor activation" factor, including psychomotor agitation and talkativeness, and a "mental activation" factor including racing/crowded thoughts were found. Different definitions (dimensional and categorical ones) of mixed depression were tested vs bipolar family history as validator (ie, MDE plus more than 1, 2, 3, and 4 concurrent hypomanic symptoms, MDE plus psychomotor agitation, MDE plus racing thoughts). Major depressive episode plus more than 1 hypomanic symptom had the highest sensitivity but the lowest specificity. Instead, MDE plus more than 4 hypomanic symptoms had the lowest sensitivity and the highest specificity. The better-balanced combination of sensitivity and specificity was shown by MDE plus more than 2 hypomanic symptoms. The same definition also showed the highest ROC area value. Multivariate regression of bipolar family history vs different mixed depression definitions found that the only strong and significant predictor was MDE plus more than 2 hypomanic symptoms. A dose-response relationship was found between the number of hypomanic symptoms during MDE and the bipolar family history loading. CONCLUSIONS: Mixed depression (MDE plus 3 or more hypomanic symptoms) was common in BP-II and MDD. A dimensional definition based on 3 or more hypomanic symptoms during depression was the most supported by using bipolar family history as validator. The study of mixed depression may be important for its possible impact on treatment (antidepressants could increase hypomanic symptoms, and mood stabilizers and antipsychotics could control hypomanic symptoms during antidepressant treatment).     

Adenosine A2A and dopamine D2 heteromeric receptor complexes and their function

The existence of A2A-D2 heteromeric complexes is based on coimmunoprecipitation studies and on fluorescence resonance energy transfer and bioluminescence resonance energy transfer analyses. It has now become possible to show that A2A and D2 receptors also coimmunoprecipitate in striatal tissue, giving evidence for the existence of A2A-D2 heteromeric receptor complexes also in rat striatal tissue. The analysis gives evidence that these heteromers are constitutive, as they are observed in the absence of A2A and D2 agonists. The A2A-D2 heteromers could either be A2A-D2 heterodimers and/or higher-order A2A -D2 hetero-oligomers. In striatal neurons there are probably A2A-D2 heteromeric complexes, together with A2A-D2 homomeric complexes in the neuronal surface membrane. Their stoichiometry in various microdomains will have a major role in determining A2A and D2 signaling in the striatopallidal GABA neurons. Through the use of D2/D1 chimeras, evidence has been obtained that the fifth transmembrane (TM) domain and/or the I3 of the D2 receptor are part of the A2A-D2 receptor interface, where electrostatic epitope-epitope interactions involving the N-terminal part of I3 of the D2 receptor (arginine-rich epitope) play a major role, interacting with the carboxyl terminus of the A2A receptor. Computerized modeling of A2A-D2 heteromers are in line with these findings. It seems likely that A2A receptor-induced reduction of D2 receptor recognition, G protein coupling, and signaling, as well as the existence of A2A-D2 co-trafficking, are the consequence of the existence of an A2A-D2 receptor heteromer. The relevance of A2A-D2 heteromeric receptor complexes for Parkinson's disease and schizophrenia is emphasized as well as for the treatment of these diseases. Finally, recent evidence for the existence of antagonistic A2A-D3 heteromeric receptor complexes in cotransfected cell lines has been summarized.     

Relationship between smoking and the clinical severity of psoriasis

OBJECTIVE: To evaluate the association between different components of smoking history and the clinical severity of psoriasis. DESIGN: A hospital-based cross-sectional study. SETTING: Inpatient wards of a hospital for skin diseases in Rome, Italy. PATIENTS: A total of 818 adults with psoriasis. MAIN OUTCOME MEASURE: The Psoriasis Area and Severity Index was used to assess the clinical severity of psoriasis between February 21, 2000, and February 19, 2002. RESULTS: After adjustment for potential confounders (sex, age, body mass index, psychological distress, family history of psoriasis, duration of psoriasis disease, and alcohol consumption), high intensity of smoking (>20 cigarettes daily) vs a lower level of consumption (< or =10 cigarettes daily) was associated with a more than 2-fold increased risk of clinically more severe psoriasis (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.2-4.1). Cigarette-years, measured as the product of the intensity and duration (years) of smoking, significantly increased the risk of clinically more severe psoriasis after adjustment for confounding factors (OR,1.3; 95% CI, 1.0-1.6, for a 600-U increase in cigarette-years). Separate analyses for men and women showed that the effect of cigarette-years was stronger for women (OR, 1.8; 95% CI, 1.2-2.6, for a 400-U increase in cigarette-years) than for men (OR, 1.2; 95% CI, 0.9-1.6, for a 700-U increase in cigarette-years). CONCLUSION: Smoking is associated with the clinical severity of psoriasis and highlights the importance of smoking cessation in patients with psoriasis.     

Unusual histological variants of cutaneous malignant melanoma with some clinical and possible prognostic correlations

Malignant melanoma is known for the wide range of histological patterns it can assume mimicking other malignant tumors. We present a review of most of the unusual histological variants of cutaneous melanoma and describe their immunohistochemical features, associate clinical findings, and possible behavior related to the histological subtype. In addition, we propose their classification into four groups corresponding to the (1) architectural patterns; (2) cytologic features; (3) stromal changes; and (4) the possible association of these findings (i.e. architectural + cytologic features). Although most of these unusual variants have the same prognosis as conventional melanomas, with Breslow thickness and ulceration, being the most important predictor of survival in clinical stage I, some of them have a peculiar biologic behavior that the clinicians and the dermatopathologists should know in order to give melanoma patients all educational information available.     

Insulin resistance causes impaired vasodilation and hypofibrinolysis in young women with polycystic ovary syndrome

INTRODUCTION: Insulin resistance, a novel cardiovascular risk factor, is often associated with increased plasminogen activator inhibitor-1 levels and impaired vasodilation. Insulin infusion in the forearm induces plasminogen activator inhibitor-1 and tissue plasminogen activator expression and endothelium-dependent vasodilation in normal subjects. The present study explores the relationship between insulin-induced vasodilatory and fibrinolytic properties of the endothelium in women with polycystic ovary syndrome, frequently affected by insulin resistance and early atherosclerosis. MATERIALS AND METHODS: Metabolic, hormonal and fibrinolytic parameters were evaluated in 64 patients with polycystic ovary syndrome (19 insulin-resistant and 45 insulin-sensitive) and in 25 controls. In 16 women with polycystic ovary syndrome, 8 insulin-resistant and 8 insulin-sensitive, blood flow, plasminogen activator inhibitor-1 and tissue plasminogen activator expression were evaluated during insulin infusion into the forearm. RESULTS: Elevated basal plasminogen activator inhibitor-1 levels were found in women with polycystic ovary syndrome, correlating directly with insulin levels. Plasminogen activator inhibitor-1 expression increased during insulin infusion in all women with polycystic ovary syndrome, but was delayed and sustained in insulin-resistant patients (p<0.01). Vasodilatory response to insulin was blunted (p<0.01) and tissue plasminogen activator expression abolished in insulin-resistant patients (p<0.01). CONCLUSION: Our study demonstrates that women with polycystic ovary syndrome and insulin resistance show a blunted endothelial-dependent vasodilation. The impaired endothelial release of tissue-plasminogen activator and the sustained plasminogen activator inhibitor-1 release during insulin infusion suggest a hypofibrinolytic state in PCOS patients with insulin resistance. This hemodynamic and fibrinolytic derangement may contribute to the pathogenesis of early atherosclerosis in insulin resistance.     

A review of dengue fever incidence in Kota Bharu, Kelantan, Malaysia during the years 1998-2003

Dengue is the most common and widespread arthropod borne arboviral infection in the world today. It is estimated that there are at least 100 million cases of dengue fever (DF) annually and 500,000 cases of dengue hemorrhagic fever (DHF) which require hospitalization. In Malaysia, it has become a major public health problem. Malaysia recorded 19,544 dengue cases in 1997, the highest recorded since the disease was made notifiable in the country. Of 19,544 cases, 806 were DHF with 50 deaths. The objectives of this analysis were to describe the incidence of dengue fever and dengue hemorrhagic fever in Kota Bharu, Kelantan, Malaysia for the years 1998-2003 and to explore the characteristics of dengue fever and dengue hemorrhagic fever in Kota Bharu, Kelantan, Malaysia for years 1998-2003. A total of 4,716 dengue cases were notified involving 4,476 (94.9%) DF and 240 (5.1%) DHF cases, which increased though the years. The highest incidence was in January (701 or 14.9%), while the lowest was in May (188 or 4.0%). Forty percent of cases (n=1,890) were in the 15-29 year old group. The Majority were Malays (4,062 or 86.1%) and 2,602 or 55.2% were male. A total of 4,477 cases (95%) were local cases and 4,289 or 91% came from the urban area. For priority areas, 3,772 (80%) were from priority 1. More than half the cases had positive serology results. All symptoms occurred in more than 96% of cases and fever was the commonest (99.7%). The mean values for age, temperature, systolic and diastolic blood pressure (BP) were 27.8 +/- 15.4 years, 37.9 +/- 0.90 degrees C, 115 +/- 15.2 mmHg and 73 +/- 11.1 mmHg, respectively. The mean value for the time interval between the onset of symptoms and diagnosis, onset of symptoms and notification and time of diagnosis to notification were 5.1 +/- 2.3, 5.9 +/- 2.5 and 0.8 +/- 1.1 days, respectively. There were associations between the types of dengue and classification, area and priority area. Among the symptoms, the association was only seen in joint pain. The mean significant differences between DF and DHF were found in age and systolic blood pressure. The incidence of dengue in Kota Bharu is comparable to that in Malaysia. The increase in the number of cases needs to be addressed promptly with effective surveillance, prevention and control programs.     

Use of Respiratory Inductance Plethysmography for the Detection of Swallowing in the Elderly

It is essential to have a user-friendly, noninvasive bedside procedure at our disposal in order to study swallowing and swallowing disorders in the elderly in view of the frailty of this age group. In the present work, respiratory inductance plethysmography (RIP) is proposed as an appropriate clinical tool for such studies. An automated process for the detection of swallowing is used involving the derivative of the respiratory volume signal. The accuracy of the automated detection is given by the area under the Receiver Operating Characteristic (ROC) curve and is found to be greater than 0.9. At the optimal threshold, RIP constitutes a reliable and objective bedside clinical tool for studying swallowing in the elderly, as well as being user-friendly and noninvasive. In addition, RIP can be used to monitor swallowing in order to analyze swallowing disorders and put in place medical supervision of swallowing for individuals who might aspirate.     

Blood pressure in adulthood and life expectancy with cardiovascular disease in men and women: life course analysis

Limited information exists about the consequences of hypertension during adulthood on residual life expectancy with cardiovascular disease. We aimed to analyze the life course of people with high blood pressure levels at age 50 in terms of total life expectancy and life expectancy with and without cardiovascular disease compared with normotensives. We constructed multistate life tables for cardiovascular disease, myocardial infarction, and stroke using data from 3128 participants of the Framingham Heart Study who had their 50th birthday while enrolled in the study. For the life table calculations, we used hazard ratios for 3 transitions (healthy to death, healthy to disease, and disease to death) by categories of blood pressure level and adjusted by age, sex, and confounders. Irrespective of sex, 50-year-old hypertensives compared with normotensives had a shorter life expectancy, a shorter life expectancy free of cardiovascular disease, myocardial infarction, and stroke, and a longer life expectancy lived with these diseases. Normotensive men (22% of men) survived 7.2 years (95% confidence interval, 5.6 to 9.0) longer without cardiovascular disease compared with hypertensives and spent 2.1 (0.9 to 3.4) fewer years of life with cardiovascular disease. Similar differences were observed in women. Compared with hypertensives, total life expectancy was 5.1 and 4.9 years longer for normotensive men and women, respectively. Increased blood pressure in adulthood is associated with large reductions in life expectancy and more years lived with cardiovascular disease. This effect is larger than estimated previously and affects both sexes similarly. Our findings underline the tremendous importance of preventing high blood pressure and its consequences in the population.