Diagnostic, prognostic and pathogenic value of the direct immunofluorescence test in cutaneous leukocytoclastic vasculitis

BACKGROUND: No precise studies have been performed on cutaneous leukocytoclastic vasculitis (LV) to establish whether it is better to obtain a skin biopsy from lesional or from perilesional skin for direct immunofluorescence (DIF). There is no agreement on the immunoglobulins most frequently detected and the value of DIF for the classification of cutaneous vasculitis. METHODS: A prospective study of DIF in lesional and perilesional skin was performed in 50 leukocytoclastic vasculitis patients and 15 nonvasculitis patients. RESULTS: We detected a higher level of positivity in involved skin than in uninvolved skin for IgG, IgA, IgM, C3 and fibrinogen but not for C1q. In vasculitic patients, IgA was the immunoglobulin most frequently detected in lesional (82%) and perilesional skin (68%), followed by IgM (56 and 34%, respectively) and IgG (20 and 8%, respectively). Only IgA deposits were associated with the diagnosis of vasculitis, with a sensitivity of 82% in lesional and 68% in perilesional skin, and with a specificity of 73 and 66.7%, respectively. The presence of IgA in lesional skin was associated with renal involvement but there was no association with severity. The presence of IgG or IgM, or the absence of IgA in perilesional skin was related to the presence of cryoglobulins. The absence of IgA in lesional and perilesional skin was also related to hepatitis C virus infection. CONCLUSIONS: DIF findings in involved skin are more closely related to the diagnosis of vasculitis and can give more information about overall renal involvement than findings in uninvolved skin. However, findings in uninvolved skin are more closely related to the pathogenic factors that trigger the development of vasculitis.     

A self-training program in inductive reasoning for low-education elderly: tutor-guided training vs. self-training

The main aim of this study was to compare the effectiveness of a self-training program in inductive reasoning run for elderly with low levels of education. Two different training settings were considered, i.e. tutor-guided training and self-training, to ascertain whether results obtained in both settings would be similar. A total of 25 subjects took part in this study (average age = 68.266, range = 60-85 years), all volunteers and residents of the city of Granada. A quasi-experimental design was used with random assignment to either training setting. The design was applied in four stages: pre-test, cognitive training (tutor-guided vs. self-trained inductive reasoning), post-test immediately after training and follow-up at 3 months. Results show considerable gains in inductive reasoning training both in tutor-guided and self-trained groups.     

Substitution at codon 22 reduces clearance of Alzheimer's amyloid-beta peptide from the cerebrospinal fluid and prevents its transport from the central nervous system into blood

A point mutation of G to C at codon 693 of the amyloid-beta (Abeta) precursor protein gene results in Glu to Gln substitution at position 22 of the Abeta (AbetaQ22) associated with hereditary cerebrovascular amyloidosis with hemorrhage Dutch type. Factors that regulate AbetaQ22 levels in the central nervous system (CNS) are largely unknown. By using ventriculo-cisternal perfusion technique in guinea pigs, we demonstrated that clearance from the cerebrospinal fluid and transport from the CNS to blood of [(125)I]-AbetaQ22 (1 nM) were reduced by 36% and 52%, respectively, in comparison to the wild type Abeta(1-40) peptide. In contrast to significant uptake and transport of Abeta(1-40) across the brain capillaries and leptomeningeal vessels, AbetaQ22 was not taken up at these CNS vascular transport sites, which was associated with its 53% greater accumulation in the brain. The CNS clearance of Abeta(1-40) was half-saturated at 23.6 nM; AbetaQ22 had about 6.8-fold less affinity for the CNS efflux transporters and its elimination relied mainly on transport across the choroid plexus. Thus, the Dutch mutation impairs elimination of Abeta from brain by reducing its rapid transport across the blood-brain barrier and the vascular drainage pathways, which in turn may result in accumulation of the peptide around the blood vessels and in brain.     

Effects of hydroxypropyl-beta-cyclodextrin on the chemical stability and the aqueous solubility of thalidomide enantiomers

The aim of this work was to study the effect of hydroxypropyl-beta-cyclodextrin on the solubility and stability of thalidomide enantiomers in aqueous solutions for clinical oral administration to be used in HIV-infected children. For this reason racemic thalidomide was added to solutions containing different concentrations of hydroxypropyl-beta-cyclodextrin. True complexes were obtained by using hydroxypropyl-beta-cyclodextrin and the solubility of both thalidomide enantiomers was increased directly depending on the amount of hydroxylpropyl-beta-cyclodextrin in the medium although no enantioselective differences were observed at 37 degrees C. The chemical stability of thalidomide enantiomers is clearly improved by hydroxypropyl-beta-cyclodextrin. No enantioselective degradation of thalidomide was observed in sodium chloride solution (0.9%) samples stored at 6 degrees C for nine days when hydroxypropyl-beta-cyclodextrin was employed as excipient. Therefore a thalidomide solution suitable for oral administration can be prepared by adding hydroxypropyl-beta-cyclodextrin at 10% (w/v).     

Correlates of Perinatal Post-Traumatic Stress among Culturally Diverse Women with Depressive Symptomatology

Post-traumatic stress disorder (PTSD) is an important and often neglected comorbidity of pregnancy; left untreated, it can lead to serious health complications for the mother and developing fetus. Structured interviews were conducted to identify risk factors of PTSD among culturally diverse women with depressive symptomatology receiving perinatal services at community obstetric/gynecologic clinics. Women abused as adults, with two or more instances of trauma, greater trauma severity, insomnia, and low social support were more likely to present perinatal PTSD symptoms. Perinatal PTSD is prevalent and has the potential for chronicity. It is imperative healthcare providers recognize salient risk factors and integrate culturally sensitive screening, appropriate referral, and treatment services for perinatal PTSD.     

Geographical distribution of the male/female ratio of cardiovascular mortality in Spain

Objectives: To describe the geographic distribution of the male/female ratio (MFR) of mortality from ischaemic heart disease (IHD) and cerebrovascular disease (CVD) in 1991-1995 in Spain, and to examine wether the differences between men and women in exposure to cardiovascular risk factors could explain such distribution.Methods: Mortality data come from National Vital Statistics. Age-adjusted mortality rates for the period 1991-1995 were calculated for IHD and CVD using the direct method, in population aged 40 to 79 years. Data on tobacco and alcohol consumption, hypertension, hypercholesterolemia, diabetes, obesity, sedentariness, and health services use come from the 1993 Spanish National Health Survey, and socioeconomic data from the 1991 Population Census. Data were analyzed by correlation and Poisson regression methods.Results: MFR of mortality from IHD and CVD are higher in the provinces of the north of Spain, and are correlated negatively with mortality from IHD and CVD. This negative association is stronger for mortality in women than in men. Among the risk factors examined, only MFR of alcohol consumption showed a significant (p < 0.05) association with MFR of mortality from IHD and CVD. MFR of alcohol consumption explains 23 and 14% of the provincial variation in MFR of mortality from IHD and CVD, respectively, and showed a U shaped relationship with MFR of mortality for both diseases.Conclusions: Provinces in the north of Spain, which register the lowest cardiovascular mortality, show the highest MFR of IHD and CVD mortality, because of the lower mortality in women than in men. As derived from the dose-response relationship between MFR of IHD and CVD mortality and the MFR of alcohol consumption, a higher alcohol consumption in men could contribute to a higher MFR of cardiovascular mortality in some Spanish provinces.     

Prospective Clinical Integration of an Amplicon-Based Next-Generation Sequencing Method to Select Advanced Non–Small-Cell Lung Cancer Patients for Genotype-Tailored Treatments

Introduction

A substantial fraction of non–small-cell lung cancers (NSCLCs) harbor targetable genetic alterations. In this study, we analyzed the feasibility and clinical utility of integrating a next-generation sequencing (NGS) panel into our routine lung cancer molecular subtyping algorithm.