Transdermal estrogen therapy effects on fibrinogen levels in women with a past history of venous thromboembolism: a pilot study

Objective: To evaluate thromboelastographic parameters and fibrinogen levels in women treated with transdermal 17 beta estradiol. Methods: 29 menopausal women with a history of venous thromboembolic disease were included. Nine patients composed the treatment (HT) group and 20 the control group. Coagulation was assessed by thromboelastography in samples of whole blood and platelet-poor plasma (PPP). The following thromboelastographic variables were measured: time for initial coagulation (R), blood clotting speed (K and the a angle), clot tensile strength (MA and G), global index of coagulation (Cl) and fibrinolysis (LY30) and fibrinogen levels. Results: There were no differences in the other parameters comparing both groups. Fibrinogen levels showed a 13.77 +/- 19.94% reduction in the HT group and a 5.51 +/- 8.09% increase in the control group after 6 months. Conclusions: Our data suggested that transdermal estrogen may not increase blood coagulability, but that it reduces fibrinogen levels in FIT women.

Effects of the association zidovudine plus ritonavir on the liver and kidneys of pregnant rats. Morphological and biochemical aspects

Purpose: To evaluate biochemical and morphological effects on rats submitted to three different doses of the association zidovudine and ritonavir administered throughout pregnancy. Methods: Forty pregnant EPM-1 Wistar rats weighing about 200 g were randomly divided into the control group (Ctr = drug vehicle control, n = 10) and three experimental ones which were treated with an oral solution of zidovudine/ritonavir (Exp1 = 10/20 mg/kg bw, n = 10; Exp2 = 30/60 mg/kg bw, n = 10; Exp3 = 90/180 mg/kg bw, n = 10) from `day 0` up to the 20th day of pregnancy. At term (20th day) the rats were anesthetized. Blood and fetal and maternal organ samples (livers and kidneys) were taken for morphological and biochemical analyses. Results: Upon histological examinations fetal livers and kidneys appeared normal. In contrast the maternal samples revealed structural alterations. Maternal kidneys of the three experimental groups exhibited progressive and dose-dependent histological alterations; liver alterations were detected only in Exp3. Blood levels of AST and ALT were not significantly different from the control group but urea and creatinine levels were lower in groups Exp3 and Exp1. Conclusions: The administration of zidovudine plus ritonavir throughout rat pregnancy can cause morphological as well as functional changes in maternal kidneys.

Dose-dependent hepatic response to subchronic administration of nandrolone decanoate

Background: Androgenic anabolic steroids (AAS) are synthetic hormone derivatives of testosterone and are mainly used to enhance athletic performance and muscle mass, but medical applications also have been described. Short- and long-term side effects have been demonstrated in many organs, but the liver adverse effects are the most common and serious ones associated with AAS use. However, these effects have been supported by few clinical and experimental studies. Objective: To evaluate the hepatic function and structure after 5 wk of nandrolone decanoate administration at three different doses. Methods: Twenty-seven adult male Wistar rats were randomly assigned to the following groups: control, clinical, intermediate, and suprapharmacological doses of nandrolone decanoate during 5 wk. Results: The biochemical studies showed that nandrolone decanoate administration leads to a dose-dependent increase in serum levels of the aspartate aminotransferase (AST) (P < 0.05), alanine aminotransferase (ALT) (P < 0.01), and alkaline phosphatase (ALP) (P < 0.001), as well as a significant decrease in total proteins (P < 0.01), bilirubin (P < 0.05), total cholesterol and fractions (P < 0.05), and triglycerides (P < 0.05). Although a significant statistical difference was found for AST, ALT, and ALP when compared with the control group, their values remained within the normal range. The number of Kupffer cells was increased in the liver parenchyma (P < 0.05), and the content of collagen was increased in the central lobular vein wall, in the hepatic parenchyma, and in the portal space (P < 0.05). Conclusions: These results suggest that subchronic treatment with nandrolone decanoate, mainly administered at higher-than-clinical doses, are potentially deleterious to the liver, leading to incipient fibrosis.

Baroreflex deficit blunts exercise training-induced cardiovascular and autonomic adaptations in hypertensive rats

P>1. Baroreceptors regulate moment-to-moment blood pressure (BP) variations, but their long-term effect on the cardiovascular system remains unclear. Baroreceptor deficit accompanying hypertension contributes to increased BP variability (BPV) and sympathetic activity, whereas exercise training has been associated with an improvement in these baroreflex-mediated changes. The aim of the present study was to evaluate the autonomic, haemodynamic and cardiac morphofunctional effects of long-term sinoaortic baroreceptor denervation (SAD) in trained and sedentary spontaneously hypertensive rats (SHR). 2. Rats were subjected to SAD or sham surgery and were then further divided into sedentary and trained groups. Exercise training was performed on a treadmill (five times per week, 50-70% maximal running speed). All groups were studied after 10 weeks. 3. Sinoaortic baroreceptor denervation in SHR had no effect on basal heart rate (HR) or BP, but did augment BPV, impairing the cardiac function associated with increased cardiac hypertrophy and collagen deposition. Exercise training reduced BP and HR, re-established baroreflex sensitivity and improved both HR variability and BPV. However, SAD in trained SHR blunted all these improvements. Moreover, the systolic and diastolic hypertensive dysfunction, reduced left ventricular chamber diameter and increased cardiac collagen deposition seen in SHR were improved after the training protocol. These benefits were attenuated in trained SAD SHR. 4. In conclusion, the present study has demonstrated that the arterial baroreflex mediates cardiac disturbances associated with hypertension and is crucial for the beneficial cardiovascular morphofunctional and autonomic adaptations induced by chronic exercise in hypertension.

Pulmonary periarterial inflammation in fatal asthma

P>Background To date, little information has been available about pulmonary artery pathology in asthma. The pulmonary artery supplies the distal parts of the lungs and likely represents a site of immunological reaction in allergic inflammation. The objective of this study was to describe the inflammatory cell phenotype of pulmonary artery adventitial inflammation in lung tissue from patients who died of asthma. Methods We quantified the different inflammatory cell types in the periarterial region of small pulmonary arteries in lung tissue from 22 patients who died of asthma [fatal asthma (FA)] and 10 control subjects. Using immunohistochemistry and image analysis, we quantified the cell density for T lymphocytes (CD3, CD4, CD8), B lymphocytes (CD20), eosinophils, mast cells (chymase and tryptase), and neutrophils in the adventitial layer of pulmonary arteries with a diameter smaller than 500 mu m. Results Our data (median/interquartile range) demonstrated increased cell density of mast cells [FA=271.8 (148.7) cells/mm

Adverse Drug Reactions and Drug Interactions as Causes of Hospital Admission in Oncology

Context. Although several studies have evaluated the frequency of adverse drug reactions (ADRs) and drug-drug interactions (DDIs) in general medicine, few studies have looked at the epidemiology of adverse drug events (ADEs) in oncology. Objectives. We sought to investigate how many hospital admissions in oncology are related to a DDI or an ADR. Methods. All cancer patients admitted to an oncology ward during an eight-month period had their charts retrospectively evaluated for reasons of hospitalization, using a 4-point scale (definitely, probably, possibly, or unlikely associated) to classify admissions by their probability of being associated with either a DDI or an ADR. Results. From September 2007 to May 2008, there were 550 hospital admissions and 458 were eligible. Among unplanned admissions (n = 298), 39 (13.0%, 95% confidence interval [CI] 9.4%-17.4%) were considered to be associated with an ADE, 33 (11.0%, 95% CI 7.7%-15.2%) with an ADR, and six (2.0%, 95% CI 0.7%-4.3%) with a DDI. The most common DDIs involved warfarin, captopril, and anti-inflammatory agents, and the most frequent ADR was neutropenic fever post-chemotherapy. Most patients were discharged completely recovered, but two patients died. Conclusion. Approximately one in 10 unplanned hospitalizations of cancer patients is associated with an ADE. Prospective and population-based studies are warranted to evaluate their magnitude in oncology. J Pain Symptom Manage 2011;42:342-353. (C) 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Nasal eosinophilia: an indicator of eosinophilic inflammation in asthma

Background It is noteworthy that there is a clear clinical, epidemiological and pathophysiological association between upper and lower airway inflammation in rhinitis and asthma. Objective The aim of this study was to compare the eosinophil counts in induced sputum and nasal lavage fluids in asthma, checking their association and the accuracy of nasal eosinophilia as a predictor of sputum eosinophilia by a cross-sectional study. Methods The clinical evaluation, asthma control questionnaire (ACQ), pre- and post-bronchodilator spirometry, nasal and sputum sample was performed. The nasal eosinophilia was analysed by a receiver operating curve and logistic regression model. Results In 140 adults, the post-bronchodilator forced expiratory volume in 1 s (FEV(1)) did not differ between patients with or without sputum eosinophilia (0.18). After adjusted for upper airway symptoms, age, ACQ score and post-bronchodilator FEV(1), sputum eosinophilia was associated with 52 times increase in odds of nasal eosinophilia, whereas each 1% increase in bronchodilator response was associated with 7% increase in odds of nasal eosinophilia. Conclusion This study brings further evidence that upper airway diseases are an important component of the asthma syndrome. Furthermore, monitoring of nasal eosinophilia by quantitative cytology may be useful as a surrogate of sputum cytology in as a component of composite measurement for determining airway inflammation.

Decreased recent thymus emigrant number in rheumatoid factor-negative polyarticular juvenile idiopathic arthritis

Objectives To determine TCR excision circle (TREC) levels, a marker of recent thymic emigrants, in the peripheral lymphocyte pool of rheumatoid factor-negative (RF circle divide) polyarticular juvenile idiopathic arthritis (JIA) children. Materials and methods We studied TREC levels in peripheral blood mononuclear cells (PBMC) in 30 RF circle divide polyarticular JIA children with active disease and in 30 age- and gender-matched healthy controls. Signal-joint TREC concentration was determined by real-time quantitative-PCR as the number of TREC copies/mu g PBMC DNA gauged by a standard curve with known number of TREC-containing plasmids. Results TREC levels in PBMC were significantly lower in JIA (4.90 +/- 3.86 x 10(4) TRECs/mu g DNA) as compared to controls (10.45 +/- 8.45 x 10(4) TRECs/mu g DNA, p=0.001). There was an inverse correlation between age and TREC levels in healthy children (r=-0.438, p=0.016) but not in JIA. No clinical association was observed between TREC levels and disease activity and use of oral steroids and methotrexate. Conclusions The finding of decreased PBMC TREC levels in RF circle divide polyarticular JIA children is consistent with a low proportion of recent thymus emigrants. This may interfere with the equilibrium between populations of polyclonal and naive T cells versus oligoclonal memory auto-reactive T cells and, therefore, may hinder the maintenance of immune tolerance in this disease.

Malformations of the index nails

We report a 52-year-old woman with micronychia of the index fingers. Radiographic examination revealed a Y-shaped bifurcation of the distal phalanx of both index fingers. She was diagnosed with congenital onychodysplasia of the index fingers (COIF) or Iso-Kikuchi syndrome. COIF is a rare condition characterized by a variety of nail dysplasia of the index fingers. Five criteria characterize COIF: congenital occurrence, unilateral or bilateral index finger involvement, variability in nail appearance, hereditary involvement and frequently associated bone abnormalities. Micronychia, polyonychia, anonychia, hemionychrogryphosis and malalignment are the observed index finger defects. Most cases have been described in Japan, and to our knowledge, this is the first case of COIF reported in South America.

Lower numbers of circulating natural killer T (NK T) cells in individuals with human T lymphotropic virus type 1 (HTLV-1) associated neurological disease

Human T lymphotropic virus type 1 (HTLV-1) infects 10-20 million people worldwide. The majority of infected individuals are asymptomatic; however, approximately 3% develop the debilitating neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is also currently no cure, vaccine or effective therapy for HTLV-1 infection, and the mechanisms for progression to HAM/TSP remain unclear. NK T cells are an immunoregulatory T cell subset whose frequencies and effector functions are associated critically with immunity against infectious diseases. We hypothesized that NK T cells are associated with HAM/TSP progression. We measured NK T cell frequencies and absolute numbers in individuals with HAM/TSP infection from two cohorts on two continents: Sao Paulo, Brazil and San Francisco, CA, USA, and found significantly lower levels when compared with healthy subjects and/or asymptomatic carriers. Also, the circulating NK T cell compartment in HAM/TSP subjects is comprised of significantly more CD4(+) and fewer CD8(+) cells than healthy controls. These findings suggest that lower numbers of circulating NK T cells and enrichment of the CD4(+) NK T subset are associated with HTLV-1 disease progression.

Agreement between stress intraocular pressure and long-term intraocular pressure measurements in primary open angle glaucoma

The aim of this paper is to study the correlation between the intraocular pressure peaks and fluctuation detected during the water drinking test and the same parameters observed during long-term follow up. This prospective cohort study enrolled 22 eyes of 22 newly diagnosed primary open angle glaucoma patients. After an initial complete ophthalmological examination, patients were started on antiglaucoma medication and returned 4 weeks later to perform the water drinking test. Thereafter, patients were evaluated at least eight times within a period of 6-12 months. The intraocular pressure peaks and fluctuation detected during the water drinking stress test were compared with those observed during regular office visits. Spearman`s correlation coefficient and Bland-Altman Plots were used for statistical analysis. The mean age of participants was 54.3 +/- 8.2 years (+/- SD), 59% were women, and average mean deviation -10.2 +/- 4.5 dB. The mean follow-up period was 8.2 +/- 2.0 months. The average intraocular pressure peaks and fluctuation during the water drinking test were 20.0 +/- 2.9 mmHg and 40 +/- 10%, respectively, and 18.1 +/- 2.8 mmHg and 30 +/- 10% during follow up. Spearman`s correlation coefficients were significant and strong between the intraocular pressure peaks and fluctuation detected during the water drinking test and during the follow-up period (P < 0.001, rho = 0.76 and 0.82, respectively). There was good agreement between the variables. The intraocular pressure peaks and fluctuation detected during the water drinking test showed significant correlation and agreement with the pressures observed during follow-up visits. Stress tests could be used to estimate long-term intraocular pressure variation.

Disseminated blue naevus and malignant blue naevus associated with excessive aromatase syndrome

We report a case of a 17-year-old boy who had a giant congenital blue naevus with multiple satellite pigmented lesions. Later the patient developed melanoma arising in the pre-existing lesion. He also had gynaecomastia and was diagnosed as having aromatase excess syndrome. To our knowledge, the association of these two rare conditions has not been previously reported. Further studies should be performed to investigate this unusual combination, which may have a genetic, endocrine or local cutaneous link leading to its occurrence.

ICAM-1 (Lys469Glu) and PECAM-1 (Leu125Val) polymorphisms in diffuse astrocytomas

Cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) play an important role in glioma invasion and angiogenesis. The aim of this study was to investigate whether specific genetic polymorphisms of ICAM-1 and PECAM-1 could be associated with glioma development and progression. Single-nucleotide polymorphism in codon 469 of ICAM-1 and codon 125 of PECAM-1 were examined in 158 patients with astrocytomas and 162 controls using polymerase chain reaction and restriction enzyme analysis. The distribution of PECAM-1 polymorphic genotypes in astrocytomas did not show any significant difference. However, a specific ICAM-1 genotype (G/G, corresponding to Lys469Glu) exhibited higher frequency in grade II astrocytomas compared to controls, grade III, and grade IV astrocytomas; suggesting that this polymorphism could be involved in the development of grade II astrocytomas.

Relationship between changes in insulin sensitivity and associated cardiovascular disease risk factors in thiazolidinedione-treated, insulin-resistant, nondiabetic individuals: pioglitazone versus rosiglitazone

This study compared the effects of administering rosiglitazone (RSG) vs pioglitazone (PIO) oil cardiovascular disease risk factors in insulin-resistant. nondiabetic individuals with no apparent disease. Twenty-two nondiabetic, apparently healthy individuals, classified as being insulin resistant oil the basis of a steady-state plasma glucose concentration of at least 10 mmol/L during the insulin suppression test, were treated with either RSG or 1110 for 3 months. Measurements were made before and after drug treatment of weight; blood pressure; fasting and daylong glucose, insulin, and free fatty acid (FFA) levels; and lipid and lipoprotein concentrations. Insulin sensitivity (steady-state plasma glucose concentration) significantly improved in both treatment groups, associated with significant decreases in daylong plasma concentrations of glucose, insulin, and FFA. Diastolic blood pressure fell somewhat in both groups, and this change reached significance in those receiving PIO. Improvement in lipid metabolism was confined to the PIO-treated group, signified by a significant decrease in plasma triglyceride concentration, whereas triglyceride concentration did not decline in the RSG-treated group, and these individuals also had increases in total (P = .047) and low-density lipoprotein cholesterol (P = .07). In conclusion, RSG and PIO appear to have comparable abilities to improve insulin sensitivity and lower daylong glucose, insulin, and FFA concentrations in nondiabetic, insulin-resistant individuals. However, despite these similarities, their effects on lipoprotein metabolism seem to be quite different, with beneficial effects confined to PIO-treated individuals. (C) 2009 Elsevier Inc. All rights reserved.