Peripheral giant cell granuloma. An immunohistochemical and ultrastructural study.

OBJECTIVE: To study the nature of multinucleated and mononuclear cells from peripheral giant cell granuloma (PGCG). MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded sections of 40 cases of PGCG were immunohistochemically stained for vimentin, alpha I-antichymotrypsin, CD68, S-100 protein, lysozyme, leucocyte common antigen (LCA), factor VIII-related antigen and muscle cell actin. Six cases of PGCG were also studied by transmission electron microscopy. RESULTS: Vimentin, alpha I-antichymotrypsin and CD68 were expressed in both the mononuclear and multinucleated giant cells. Dendritic mononuclear cells, positive for S-100 protein, were noted in 67.5% of the lesions, whereas lysozyme and leucocyte common antigen were detected in occasional mononuclear cells. Ultrastructural examination showed mononuclear cells with signs of phagocytosis and sometimes interdigitations with similar cells. Others presented non-specific characteristics and the third type exhibited cytoplasmic processes and occasional Birbeck granules. Some multinucleated giant cells showed oval nuclei, abundant mitochondria and granular endoplasmic reticulum whereas others presented with irregular nuclei and a great number of cytoplasmic vacuoles. CONCLUSIONS: Immunohistochemical and ultrastructural results suggest that PGCGs of the jaws are composed mainly of cells of the mononuclear phagocyte system and that Langerhans cells are present in two thirds of the lesions.

Is chronic hypoxemia in patients with chronic obstructive pulmonary disease associated with more marked nutritional deficiency?: A study of the fat-free mass evaluated by anthropometry and bioelectrical impedance methods

In order to determine wheter blood gases abnormalities, specially hypoxemia, are associated with more marked changes in fat-free mass in patients with chronic obstructive pulmonary disease (CPOD), nutritional assessment was performed on 16 normoxemic (PaO 2 > 55 mm Hg) and 16 hypoxemic (PaO 2 < 55 mm Hg) COPD patients in stable clinical condition. Body weight was expressed as percentage of the ideal body weight. Fat-free mass was estimated by anthropometry (FFM-Anthr) and by bioelectrical impedance (FFM- BI). Handgrip-strength was assessed as a measure of peripheral skeletal muscle strength. Patients were age-matched and presented similar degree of airway obstruction. Malnutrition, defined as body weight less than 90% of the ideal, was observed in 19% of the normoxemic patients and in 25% of the hypoxemic patients (p>0,05). FFM values in hypoxemic patients, estimated by both methods, were not different from those observed in normoxemic patients. No significant difference was observed on handgrip values between the two groups. No correlation was found between nutritional indices and pulmonary function and gases exchange parameters. FFM correlated positively with values of peripheral muscle function in normoxemic and hypoxemic patients. These data add further evidence to the hypothesis that hypoxemia is not a primary cause of the nutritional deficiency observed in COPD patients.

Cytokines and dietary energy restriction in stable chronic obstructive pulmonary disease patients

Tumour necrosis factor (TNF)-α has been found to be increased in malnourished chronic obstructive pulmonary disease (COPD) patients; however, the main cause of this phenomenon remains undetermined. In normal subjects, TNF-α production may be induced by dietary energy deprivation. The aim of this study was to investigate if stable COPD patients present alterations of inflammatory mediators after 48 h of dietary energy restriction. Fourteen COPD patients were admitted to the hospital while receiving an experimental diet with an energy content of approximately one-third of their energy needs. Clinical evaluation, nutritional assessment and serum levels of interleukin (IL)-6, TNF-α and C-reactive protein, and secretion of TNF-α by peripheral blood monocytes were assessed on admission and after the experimental diet. For reference values of the laboratory parameters, blood was collected from 10 healthy, elderly subjects. COPD patients showed significantly higher serum concentrations of IL-6 than control subjects, however, the experimental diet was not associated with statistically significant changes in the inflammatory mediators. The findings of this study, although preliminary because of the limited degree and duration of the energy restriction, suggest that the elevated levels of tumour necrosis factor-α, previously described in undernourished or weight-losing chronic obstructive pulmonary disease patients, may not be linked to a decrease of dietary energy intake.

Use of skin graft punch graft type for the healing of leg ulcers in treated Hansen's disease patients

Hansen's disease is an infectious illness caused by Mycobacterium leprae. It affects preferentially the skin and the peripheral nervous system leading to incapacities, such as leg ulcers, which happens due to the direct action of the bacillus on the organs or its indirect action on the peripheral nervous system. Leg ulcers can occur by two physiopathologic processes. There are many treatments for general leg ulcers, which include the ones caused by Hansen's disease sequels. Among them, surgical treatment shows to be effective when using skin graft, which can be performed by several techniques. Considering the low number of techniques known for treating leg ulcers in Hansen's disease sequels, the aims of this work were to standardize alternative techniques, to detect the main bacteria found in ulcer secretion cultures, to analyze the patients profile and the ulcers, to describe the histophatologies found, and to correlate these data with those of literature from all over the world. Skin graft punch type was carried out and analyzed; males had a mean age of 59.4 years old and females, 54.2 years old. Patients were 73.6% male and 26.3% female. Lepromatous type was present in 89.4% patients and tuberculoid type was seen in 10.5% of them. Associated systemic diseases were observed in 26.3% patients. Mean time of ulcers evolution was 11.6 years in male and 12.8 years in women. The average diameter of ulcers in the pre-treatment period was 8.5 X 9.5 cm in male and 10.2 X 6.8 cm in women. After the graft, their average diameters were 3.2 X 2.7 cm in male and 5.1 X 5.6 cm in women. Statistical analysis showed that there was no significant correlation between the ulcer diameter and its reduction or not in the post-surgery period (p=0.269732). The mean age of patients whose ulcers diameter did not change or reduced by only 20% was 63.5 years. Using the Spearman's coefficient, it was possible to observe that there was no significant correlation between the patients' age and the ulcers diameter reduction after the skin graft (p=0.222531). Evolution time of ulcers that did not present any satisfactory result in the post-surgery period was 12.1 years. The Spearman's coefficient showed that there was no significant correlation between the ulcers evolution time and the ulcers diameter reduction in the post-surgery period (p=0.191655). Cultures presented 50% of cases with Pseudomonas aeruginosa. Statistical analysis showed there is no correlation between the bacterial types found and the ulcer evolution in the post-surgery period (p=0.697531). The average of the ulcers diameter reduction was 42.4%, and in 26.3% of the patients the lesions disappeared after the skin graft.

Risk factors for vascular dementia in elderly psychiatric outpatients with preserved cognitive functions

The aim of the study was to assess risk factors for vascular dementia (VaD) in elderly psychiatric outpatients without dementia, and to determine to what extent clinical interventions targeted such risk factors. Out of 250 clinical charts, 78 were selected of patients over 60 years old, who showed no signs of dementia. Information was obtained regarding demographics, clinical conditions (diagnosis according to ICD-10), complementary investigation, cognitive functions (via CAMCOG), neuroimaging, and the presence of risk factors for VaD. Depression was the most prevalent psychiatric disorder (74%). A great majority of the patients (86%) had at least one risk factor for VaD. One-third of the sample showed three or more risk factors for VaD. The clinical conditions related to risk factors for VaD were hypertension (48.7%), heart disease (30.8%), hypercholesterolemia (25.6%), diabetes mellitus (23.1%), stroke (12.8%), tryglyceride (12.8%), and obesity (5.1%). In terms of lifestyle, smoking (19.2%), alcohol abuse (16.7%), and sedentarism (14.1%) were other risk factors found. Definite risk factors for VaD were found in 83.3% of the patients. Previous interventions targeting risk factors were found in only 20% of the cases. The high rates of risk factors for VaD identified in this sample suggest that psychiatrists should be more attentive to these factors for the prevention of VaD. © 2007 Elsevier B.V. All rights reserved.

Vascular hyporeactivity to angiotensin II induced by Escherichia coli endotoxin is reversed by Nω-Nitro-L-Arginine, an inhibitor of nitric oxide synthase

Septic shock or sepsis is reported to be one of the major causes of death when followed by systemic infectious trauma in humans and other mammals. Its development leads to a large drop in blood pressure and a reduction in vascular responsiveness to physiological vasoconstrictors which, if not contained, can lead to death. It is proposed that this vascular response is due to the action of bacterial cell wall products released into the bloodstream by the vascular endothelium and is considered a normal response of the body's defenses against infection. A reduction in vascular reactivity to epinephrine and norepinephrine is observed under these conditions. In the present study in rats, the aim was to assess whether those effects of hypotension and hyporeactivity are also related to another endogenous vasoconstrictor, angiotensin II (AII). We evaluated the variation in the power of this vasoconstrictor over the mean arterial pressure in anesthetized rats, before and after the establishment of hypotension by Escherichia coli endotoxin (Etx). Our results show that in this model of septic shock, there is a reduction in vascular reactivity to AII and this reduction can be reversed by the inhibitor of nitric oxide synthase, Nω-Nitro-L- Arginine (NωNLA). Our results also suggest that other endogenous factors (not yet fully known) are involved in the protection of rats against septic shock, in addition to the L-arginine NO pathway.

Treatment of atherosclerotic renovascular disease

Treatment of atherosclerotic renovascular disease is controversial and revascularization is not a beneficial approach to all patients. Conditions as progressive deterioration of renal function, refractory hypertension or accelerated cardiovascular disease, especially recurrent pulmonary edema, could profit from renal angioplasty with stent placement. Surgical revascularization is a good option for patients who will need concomitant surgical corrections of abdominal aortic lesions. Treatment of all other patients must be individualized. Medical therapy is indicated for all patients with atherosclerotic renovascular disease. Observational studies pointed out to the beneficial effect of controlling blood pressure (<130/80 mm Hg), glucose and lipids profile, lifestyle modifications, specific use of platelet antiaggregant therapy, Angiotensin Conversion Enzyme Inhibitors (ACEI) and statins. All others cardiovascular risk factors must be controlled. The evaluation and management of other systemic atherosclerotic vascular lesions is important, especially coronary, carotid and abdominal aortic. This paper presents a review of evidences to rationale the atherosclerotic renovascular disease treatment. © 2008 Bentham Science Publishers Ltd.

Functional activity of neutrophils and systemic inflammatory response of Down's syndrome patients with periodontal disease

Periodontal disease (PD) is characterized as an inflammatory process that compromises the support and protection of the periodontium. Patients with Down's syndrome (DS) are prone to develop PD. Neutrophils (NE) are the first line of defense against infection and their absence sets the stage for disease. Aim: To compare the activity and function of NE in the peripheral blood from DS patients with and without PD, assisted at the Center for Dental Assistance to Patients with Special Needs affiliated with the School of Dentistry of Araçatuba, Brazil. Methods: Purified NE were collected from peripheral blood of 22 DS patients. NE were used to detect the 5-lypoxigenase (5-LO) expression by RT-PCR. Plasma from peripheral blood was collected to measure tumor necrosis factor-a (TNF-α) and interleukin-8 (IL-8) by ELISA and nitrite (NO 3) using a Griess assay. Results: Data analysis demonstrated that DS patients with PD present high levels of TNF-a and IL-8 when compared with DS patients without PD. However, there was no statistically significant difference in the levels of NO 3 production between the groups. The levels of the inflammatory mediator 5-LO expression increased in DS patients with PD. Conclusions: According with these results, it was concluded that TNF-α and IL-8 are produced by DS patients with PD. Furthermore, DS patients with PD presented high levels of 5-LO expression, suggesting the presence of leukotriene B 4 (LTB 4) in PD, thus demonstrating that the changes in NE function due to the elevation of inflammatory mediators contribute to PD.

Enzyme replacement therapy for Anderson-Fabry disease.

Anderson-Fabry disease is an X-linked defect of glycosphingolipid metabolism. Progressive renal insufficiency is a major source of morbidity, additional complications result from cardio- and cerebro-vascular involvement. Survival is reduced among affected males and symptomatic female carriers. To evaluate the effectiveness and safety of enzyme replacement therapy compared to other interventions, placebo or no interventions, for treating Anderson-Fabry disease. We searched 'Clinical Trials' on The Cochrane Library, MEDLINE, EMBASE, LILACS and the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register (date of the most recent search: 11 September 2012). The original search was performed in September 2008.Date of the most recent search of the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register: 11 September 2012. Randomized controlled trials of agalsidase alfa or beta in participants diagnosed with Anderson-Fabry disease. Two authors selected relevant trials, assessed methodological quality and extracted data. Six trials comparing either agalsidase alfa or beta in 223 participants fulfilled the selection criteria.Both trials comparing agalsidase alfa to placebo reported on globotriaosylceramide concentration in plasma and tissue; aggregate results were non-significant. One trial reported pain scores, there was a statistically significant improvement for participants receiving treatment at up to three months, mean difference -2.10 (95% confidence interval (CI) -3.79 to -0.41); at up to five months, mean difference -1.90 (95% CI -3.65 to -0.15); and at up to six months, mean difference -2.00 (95% CI -3.66 to -0.34). There was a significant difference in pain-related quality of life at over five months and up to six months, mean difference -2.10 (95% CI -3.92 to -0.28) but not at other time-points. Neither trial reported deaths.One of the three trials comparing agalsidase beta to placebo reported on globotriaosylceramide concentration in plasma and tissue and showed significant improvement: kidney, mean difference -1.70 (95% CI -2.09 to -1.31); heart, mean difference -0.90 (95% CI -1.18 to -0.62); and composite results (renal, cardiac, and cerebrovascular complications and death), mean difference -4.80 (95% CI -5.45 to -4.15). There was no significant difference between groups for death; no trials reported on pain.Only one trial compared agalsidase alfa to agalsidase beta. There was no significant difference between the groups for any adverse events, risk ratio 0.36 (95% CI 0.08 to 1.59), or any serious adverse events; risk ratio 0.30; 95% CI 0.03 to 2.57). Six small, poor quality randomised controlled trials provide no robust evidence for use of either agalsidase alfa and beta to treat Anderson-Fabry disease.

Effects of active smoking on airway and systemic inflammation profiles in patients with chronic obstructive pulmonary disease

Background: The markers that characterize local and systemic inflammation in chronic obstructive pulmonary disease (COPD) remain unclear, as do their correlations with smoking status and presence of disease. The aim of this study was to assess markers of inflammation in the peripheral blood and airways of current smokers without COPD, of current smokers with COPD and of ex-smokers with COPD. METHODS: In this study, 17 current smokers with COPD (mean age: 58.2 ± 9.6 years; mean forced expiratory volume in 1 second [FEV1]: 56.1 ± 15.9%), 35 ex-smokers with COPD (mean age: 66.3 ± 7.3 years; mean FEV1: 47.9 ± 17.2%) and 20 current smokers without COPD (mean age: 49.1 ± 6.2 years; mean FEV1: 106.5 ± 15.8%) were evaluated. Spirometry findings, body composition and serum/induced sputum concentrations of tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-8 and IL-10, together with serum C-reactive protein (CRP) levels, were assessed. RESULTS: Serum TNF-α concentration was higher in all current smokers than in ex-smokers with COPD. In current smokers without COPD, serum CRP level was lower than in ex-smokers with COPD and significantly lower than in current smokers with COPD. Sputum TNF-α concentration was higher in current and ex-smokers with COPD than in current smokers without COPD. Multiple regression analyses showed that serum TNF-α was associated with active smoking, and serum CRP and sputum TNF-α were associated with COPD diagnosis. CONCLUSIONS: Smoking is associated with higher systemic inflammation in patients with COPD. Current findings also support the hypothesis that smoking and COPD have different effects on the regulation of airway and systemic inflammatory processes. © 2013 Lippincott Williams and Wilkins.

CD95 (FAS) and CD178 (FASL) induce the apoptosis of CD4+ and CD8+ cells isolated from the peripheral blood and spleen of dogs naturally infected with Leishmania spp

Infected dogs are urban reservoirs of Leishmania chagasi, which is a causative agent of visceral leishmaniasis (VL). Dogs exhibit immune suppression during the course of this disease, and lymphocyte apoptosis is involved in this process. To investigate apoptosis and the expression levels of FAS-FAS-associated death domain protein (CD95 or APO-1), FASL-FAS ligand protein (CD178), and TRAIL-TNF-related apoptosis-inducing ligand (CD253) receptors in peripheral blood mononuclear cells and spleen leukocytes from 38 symptomatic dogs with moderate VL and 25 healthy dogs were evaluated by flow cytometry. The apoptosis rate of blood and splenic CD4+ and CD8+ cells was higher in infected dogs than in healthy dogs. The expression levels of FAS and FASL in blood and splenic CD4+ cells were lower in infected dogs than in healthy dogs. FAS expression in CD8+ cells was higher in infected dogs than in healthy dogs; in contrast, FASL expression was lower in infected dogs. The expression of the TRAIL receptor increased only in splenic CD8+ cells from infected dogs. The FAS and FAS-L blocking antibodies confirmed the importance of these receptors in apoptosis. Our results enhance the current understanding of the immune response in dogs infected with L. chagasi, facilitating the future development of therapeutic interventions to reduce lymphocyte depletion. © 2013 Elsevier B.V.