Cyclophosphamide effect on coccidioidomycosis in the rat

Coccidioidomycosis is a systemic mycosis, endemic in arid areas of the American continent. The rat was employed as an experimental host, since it had been shown to reproduce human lesions and present a chronic course of disease with granulomas mainly restricted to lungs. Given the influence of immunosuppressive therapy on the clinical course of human coccidioidomycosis, we studied the effect of cyclophosphamide (CY) in the experimental rat model. Accordingly, animals were inoculated with 400 Coccidioides immitis arthroconidia of the Acosta strain, by intracardiacal route. As single CY doses failed to alter the course of disease, three schedules were used: A) 4 daily doses of 20 mg/kg each, prior to C. immitis inoculation; B) 4 similar daily doses after infection; and C); 6 doses of 20 mg/kg each, given from day +1 to +4, then on days +8 and +9, post infection (pi), taking day 0 as the time of fungal inoculation. The first two schedules inhibited antibody formation up to day 28 pi, without modifying cellular response to coccidioidin as measured by foodpad swelling. Initially, there was greater fungal spread than in controls receiving C. immitis alone, which proved self-limiting in the latter. In contrast, schedule C led to 559r mortality, with both humoral and cellular response abrogation, accompanied by extensive C. immitis dissemination. Histology disclosed significant alterations, such as the persistence of primary infection sporangia, corresponding to the acute stage of coccidioidomycosis in the absence of granuloma development. Therefore, the observed depression in cellular immunity seems responsible for the lack of inflammatory reaction capable of restricting sporangia proliferation in tissues which, in turn, enhances pathogen spread and mortality rate.

Pathology of periportal fibrosis involution in human schistosomiasis

Optical and electron microscopical evidences of focal matrix degradation were frequently seen in liver sections of periportal fibrosis caused by schistosomiasis mansoni in man. The material came from 14 wedge hepatic biopsies taken from patients with chronic advanced hepatosplenic disease and undergoing operations for the relief of portal hypertension. Besides the presence of focal areas of rarefaction, fragmentation and dispersion of collagen fibers, the enlarged portal spaces also showed hyperplasia of elastic tissue and disarray of smooth muscle fibers following destruction of portal vein branches. Eggs were scanty in the tissue sections, and matrix degradation probably represented involuting changes related to the progressive diminution of parasite-related aggression, which occurs spontaneously with age or after cure by chemotherapy. The changes indicative of matrix degradation now described are probably the basic morphological counterpart of periportal fibrosis involution currently being documented by ultrasonography in hepatosplenic patients submitted to curative chemotherapy.

Cutaneous Nocardia asteroides infection of nontraumatic origin

This paper reports a case of cutaneous infection of nontraumatic origin caused by Nocardia asteroides in a hospitalized patient with chronic obstructive pulmonary disease. Diagnosis was established by direct and histological examination, cultures from exudate and biopsy specimen. We discuss the classification of clinical forms of Nocardia infections affecting the skin.

Human T-cell lymphotropic virus types I and II infections in a cohort of patients with neurological disorders in Belém, Pará, Brazil

Serum- and/or- cerebrospinal fluid (CSF) samples obtained from 190 patients suffering from chronic, progressive neurological disease were screened for the presence of human T-cell lymphotropic viruses type I (HTLV-I) and type II (HTLV-II) antibodies over a six-year period (1996 to 2001) in Belém, Pará, Brazil. Patients were of both sexes (male subjects, 52%) with ages ranging from 2 to 79 years (mean, 35.9). Overall, 15 (7.9%) subjects - of whom 12 (80%) were female adults - reacted HTLV-I/II-seropositive when screened by enzyme-linked immunosorbent assay (ELISA). Serum samples from 14 of these patients were also analyzed using a recombinant Western blot (WB) assay that yielded HTLV-I-, HTLV-II-, and HTLV-I/II- reactivities for 10 (71.4%), 3 (21.4%) and 1 (7.2%) of them, respectively. The yearly rates of HTLV-I/II antibodies ranged from 2.6% (2001) to 21.7% (2000), with progressively increasing seropositivities from 1998 to 2000. Altogether, walking difficulty (n = 5 subjects), spasticity (n = 4) and leg weakness (n = 3) accounted for 80% of symptoms recorded among the 15 patients whose sera had antibodies to HTLV-I/II as detected by ELISA. These findings provide evidence that both HTLV-I and HTLV-II play a role in the development of chronic myelopathy in Belém, Pará, Northern Brazil.

Sea urchin granuloma

Injuries caused by venomous and poisonous aquatic animals may provoke important morbidity in humans. The phylum Echinoderma include more than 6000 species of starfish, sea urchins, sand dollars, and sea cucumbers some of which have been found responsible for injuries to humans. Initial injuries by sea urchins are associated with trauma and envenomation, but later effects can be observed. Sea urchin granuloma is a chronic granulomatous skin disease caused by frequent and successive penetration of sea urchin spines which have not been removed from wounds. The authors report a typical case of sea urchin granuloma in a fisherman and its therapeutic implications.

Characteristics and identification of sites of chagasic ventricular tachycardia by endocardial mapping

OBJECTIVE: To study electrophysiological characteristics that enable the identification and ablation of sites of chagasic tachycardia. METHODS: Thirty-one patients with chronic Chagas' heart disease and sustained ventricular tachycardia (SVT) underwent electrophysiological study to map and ablate that arrhythmia. Fifteen patients had hemodinamically stable SVT reproducible by programmed ventricular stimulation, 9 men and 6 women with ages ranging from 37 to 67 years and ejection fraction varying from 0.17 to 0.64. Endocardial mapping was performed during SVT in all patients. Radiofrequency (RF) current was applied to sites of presystolic activity of at least 30 ms. Entrainment was used to identify reentrant circuits. In both successful and unsuccessful sites of RF current application, electrogram and entrainment were analyzed. RESULTS: Entrainment was obtained during all mapped SVT. In 70.5% of the sites we observed concealed entrainment and ventricular tachycardia termination in the first 15 seconds of RF current application. In the unsuccessful sites, significantly earlier electrical activity was seen than in the successful ones. Concealed entrainment was significantly associated with ventricular tachycardia termination. Bystander areas were not observed. CONCLUSION: The reentrant mechanism was responsible for the genesis of all tachycardias. In 70.5% of the studied sites, the endocardial participation of the slow conducting zone of reentrant circuits was shown. Concealed entrainment was the main electrophysiological parameter associated with successful RF current application. There was no electrophysiological evidence of bystander regions in the mapped circuits of SVT.

Rheumatic carditis treated with high doses of pulsetherapy methylprednisolone. Results in 70 children over 12 years

PURPOSE: To report the result of patients treated with IV methylprednisolone divided into three groups and compare their follow-up during the last 12 years. METHODS: Seventy children with active rheumatic carditis (76 episodes) in heart failure Class III and IV (NYHA) were studied. The diagnosis was based on modified Jones' criteria. After ruling out infections and strongyloidiasis, treatment with IV methylprednisolone bolus was started three times a week until the laboratory tests became negative. Patients were divided into 3 groups, according to the time of hospital admittance: Groups 1, 2 and 3, comprising of 40, 18 and 12 children, respectively. RESULTS: Eighteen children in Group 1 (45%) were in their 1st attack: 2 series of pulsetherapy were used in 10 (25%), 3 in 9 (23%) and 4 in 21 (52%). In Group 2, 14 cases (77%) were in their 1st attack: 2 series were used in 7 (39%), 4 in 9 (50%) and 5 in 2 (11%). The echocardiogram showed a flail mitral valve in 12 (66%) of these patients (1 death occurred after mitral valvoplasty). In Group 3, 6 patients needed 5 or more series of pulsetherapy and a flail mitral valve was present in 5 (41%). One child underwent mitral valve replacement while still in the active phase, after 8 series of pulsetherapy, and another died. The number of patients who needed 5 or more series was significantly higher in Group 3. CONCLUSION: There were variations in the presentation and evolution of the cases during these 12 year. The established pulsetherapy protocol continues to be useful to treat severe cases.

Healthcare-Associated Infective Endocarditis: a Case Series in a Referral Hospital from 2006 to 2011

Background: Healthcare-associated infective endocarditis (HCA-IE), a severe complication of medical care, shows a growing incidence in literature. Objective: To evaluate epidemiology, etiology, risk factors for acquisition, complications, surgical treatment, and outcome of HCA-IE. Methods: Observational prospective case series study (2006-2011) in a public hospital in Rio de Janeiro. Results: Fifty-three patients with HCA-IE from a total of 151 cases of infective endocarditis (IE) were included. There were 26 (49%) males (mean age of 47 ± 18.7 years), 27 (51%) females (mean age of 42 ± 20.1 years). IE was acute in 37 (70%) cases and subacute in 16 (30%) cases. The mitral valve was affected in 19 (36%) patients and the aortic valve in 12 (36%); prosthetic valves were affected in 23 (43%) patients and native valves in 30 (57%). Deep intravenous access was used in 43 (81%) cases. Negative blood cultures were observed in 11 (21%) patients, Enterococcus faecalis in 10 (19%), Staphylococcus aureus in 9 (17%), and Candida sp. in 7 (13%). Fever was present in 49 (92%) patients, splenomegaly in 12 (23%), new regurgitation murmur in 31 (58%), and elevated C-reactive protein in 44/53 (83%). Echocardiograms showed major criteria in 46 (87%) patients, and 34 (64%) patients were submitted to cardiac surgery. Overall mortality was 17/53 (32%). Conclusion: In Brazil HCA-IE affected young subjects. Patients with prosthetic and native valves were affected in a similar proportion, and non-cardiac surgery was an infrequent predisposing factor, whereas intravenous access was a common one. S. aureus was significantly frequent in native valve HCA-IE, and overall mortality was high.

Atrial Fibrillation and Non-cardiovascular Diseases: A Systematic Review

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an unfavorable prognosis, increasing the risk of stroke and death. Although traditionally associated with cardiovascular diseases, there is increasing evidence of high incidence of AF in patients with highly prevalent noncardiovascular diseases, such as cancer, sepsis, chronic obstructive pulmonary disease, obstructive sleep apnea and chronic kidney disease. Therefore, considerable number of patients has been affected by these comorbidities, leading to an increased risk of adverse outcomes.The authors performed a systematic review of the literature aiming to better elucidate the interaction between these conditions.Several mechanisms seem to contribute to the concomitant presence of AF and noncardiovascular diseases. Comorbidities, advanced age, autonomic dysfunction, electrolyte disturbance and inflammation are common to these conditions and may predispose to AF.The treatment of AF in these patients represents a clinical challenge, especially in terms of antithrombotic therapy, since the scores for stratification of thromboembolic risk, such as the CHADS2 and CHA2DS2VASc scores, and the scores for hemorrhagic risk, like the HAS-BLED score have limitations when applied in these conditions.The evidence in this area is still scarce and further investigations to elucidate aspects like epidemiology, pathogenesis, prevention and treatment of AF in noncardiovascular diseases are still needed.

Protective Effect of Aortic Stenosis on the Coronary Arteries. Hypothetic Considerations to an Old Enigma

Abstract A literature overview of angiographic studies has shown that the prevalence of significant coronary disease in patients with aortic stenosis (AS) varies from 20 to 60%. Early necropsy studies suggested that patients with AS had a lower than expected incidence of coronary artery disease (CAD), originating the concept of a protective effect of AS on the coronary arteries. The myth of AS protection against CAD would be better explained as endothelium-myocardial interaction (crosstalk) protection triggered by left ventricular overload. Therefore, the cGMP/NO pathway induced by the AS overload pressure would explain the low incidence of CAD, which is compatible with the amazing natural long-term evolution of this cardiac valve disease.

Macrophage elastase (MMP-12): a pro-inflammatory mediator?

As many metalloproteinases (MMPs), macrophage elastase (MMP-12) is able to degrade extracellular matrix components such as elastin and is involved in tissue remodeling processes. Studies using animal models of acute and chronic pulmonary inflammatory diseases, such as pulmonary fibrosis and chronic obstrutive pulmonary disease (COPD), have given evidences that MMP-12 is an important mediator of the pathogenesis of these diseases. However, as very few data regarding the direct involvement of MMP-12 in inflammatory process in the airways were available, we have instilled a recombinant form of human MMP-12 (rhMMP-12) in mouse airways. Hence, we have demonstrated that this instillation induced a severe inflammatory cell recruitment characterized by an early accumulation of neutrophils correlated with an increase in proinflammatory cytokines and in gelatinases and then by a relatively stable recruitment of macrophages in the lungs over a period of ten days. Another recent study suggests that resident alveolar macrophages and recruited neutrophils are not involved in the delayed macrophage recruitment. However, epithelial cells could be one of the main targets of rhMMP-12 in our model. We have also reported that a corticoid, dexamethasone, phosphodiesterase 4 inhibitor, rolipram and a non-selective MMP inhibitor, marimastat could reverse some of these inflammatory events. These data indicate that our rhMMP-12 model could mimic some of the inflammatory features observed in COPD patients and could be used for the pharmacological evaluation of new anti-inflammatory treatment. In this review, data demonstrating the involvement of MMP-12 in the pathogenesis of pulmonary fibrosis and COPD as well as our data showing a pro-inflammatory role for MMP-12 in mouse airways will be summarized.

Study of the cardiac left atrioventricular valvar complex in water buffaloes (Bubalus bubalis) of the Jafarabadi breed

Atrioventricular valve complex of 30 Jafarabadi water buffaloes, adult males were studied in this research with no heart diseases. The animals were obtained from a slaughterhouse in Brazilian State of Parana. The hearts were opened at the third portion affording access to the valve complex. The complexes had its area, number and type of tendinous cords submitted to analysis. The results showed that the complex is composed by two cusps and four accessory cusps, two or three papillary muscles in which 10-25 tendinous cords fix on the cusps that face the ventricle wall. The total area of the complex was on average 38.56cm², with a minimum of 24.96cm² and a maximum of 55.54cm². Statistically, no relation between the number of cords and the cusps' area where they are inserted or with the number of papillary muscle where they originated from was observed.

Morphological changes of carotid bodies in acute respiratory distress syndrome: a morphometric study in humans

Carotid bodies are chemoreceptors sensitive to a fall of partial oxygen pressure in blood (hypoxia). The morphological alterations of these organs in patients with chronic obstructive pulmonary disease (COPD) and in people living at high altitude are well known. However, it is not known whether the histological profile of human carotid bodies is changed in acute clinical conditions such as acute respiratory distress syndrome (ARDS). The objective of the present study was to perform a quantitative analysis of the histology of carotid bodies collected from patients who died of ARDS. A morphometric study of carotid bodies collected during routine autopsies was carried out on three groups: patients that died of non-respiratory diseases (controls, N = 8), patients that presented COPD and died of its complications or associated diseases (N = 7), and patients that died of ARDS (N = 7). Morphometric measurements of the volume fraction of clusters of chief cells were performed in five fields on each slide at 40X magnification. The numerical proportion of the four main histological cell types (light, dark, progenitor and sustentacular cells) was determined analyzing 10 fields on each slide at 400X magnification. The proportion of dark cells was 0.22 in ARDS patients, 0.12 in controls (P<0.001), and 0.08 in the COPD group. The proportion of light cells was 0.33 (ARDS), 0.44 (controls) (P<0.001), and 0.36 (COPD). These findings suggest that chronic and acute hypoxia have different effects on the histology of glomic tissue.

Role of matrix metalloproteinases in the development of airway inflammation and remodeling

Matrix metalloproteinases (MMPs) are a major group of proteases known to regulate extracellular matrix (ECM) turnover and so they have been suggested to be important in the process of lung disease associated with tissue remodeling. This has led to the concept that modulation of airway remodeling including excessive proteolysis damage to the tissue may be of interest for future treatment. Within the MMP family, macrophage elastase (MMP-12) is able to degrade ECM components such as elastin and is involved in tissue remodeling processes in chronic obstructive pulmonary disease including emphysema. Pulmonary fibrosis has an aggressive course and is usually fatal within an average of 3 to 6 years after the onset of symptoms. Pulmonary fibrosis is associated with deposition of ECM components in the lung interstitium. The excessive airway remodeling as a result of an imbalance in the equilibrium of the normal processes of synthesis and degradation of ECM components could justify anti-protease treatments. Indeed, the correlation of the differences in hydroxyproline levels in the lungs of bleomycin-treated mice strongly suggests that a reduced molar pro-MMP-9/TIMP-1 ratio in bronchoalveolar lavage fluid is associated with collagen deposition, beginning as early as the inflammatory events at day 1 after bleomycin administration. Finally, these observations emphasize that effective treatment of these disorders must be started early during the natural history of the disease, prior to the development of extensive lung destruction and fibrosis.