Clinicopathological and virological characteristics of superficially invasive squamous-cell carcinoma of the anus.

AIM: The clinicopathological and virological characteristics of anal superficially invasive squamous-cell carcinoma (SISCCA) were determined. METHOD: Seventeen patients with a completely excised stage T1N0M0 anal squamous-cell carcinoma (SCC) were included in the study. The tumours were divided into superficially invasive and invasive. Patients with anal high-grade squamous intraepithelial dysplasia, which corresponded to anal intraepithelial neoplasia (AIN) Grades 2 or 3, were used as a control group. Clinicopathological and virological characteristics were investigated. Overall survival and cancer recurrence-free survival were also assessed. RESULTS: Of the 17 patients, 12 (70.5%) were men. Ten (58.8%) were human immunodeficiency virus positive. Seven (41%) patients met the same diagnostic criteria as those recently proposed for anal SISCCA. According to the results obtained using the polymerase chain reaction, human papillomavirus (HPV) 16 was the most commonly detected (94%) type of HPV. Twelve (70.6%) patients with an inadequate surgical margin around the tumour received adjuvant radiotherapy, including the two (11.7%) tumours that locally recurred, one of which was an anal SISCCA. Superficially invasive anal cancers differed from the other T1N0M0 anal carcinomas according to the clinical presentation and the absence of lymph-vascular invasion (LVI). There were no differences in cancer recurrence-free and overall survival rates between the superficially invasive and invasive groups. CONCLUSION: Anal SISCCAs have a low index of clinical suspicion, are associated with an absence of LVI and are linked to high-risk HPV. Prospective studies are needed to define the clinical behaviour of these anal tumours and to determine their best therapeutic strategy.

Assessing health-related quality of life among coronary patients: SF-36 vs SF-12.

OBJECTIVE: to compare health-related quality of life (HRQL) assessed using the Short Form-12 (SF-12) and the Short Form-36 (SF-36) questionnaires in coronary patients with different diagnoses, testing the hypothesis that the SF-12 is capable of discriminating between patients with acute myocardial infarction (AMI) and patients with unstable angina in the same way as the SF-36. STUDY DESIGN: Cross-sectional study. METHODS: HRQL was studied in 186 patients admitted to hospital for ischaemic cardiopathy, using the SF-36 and SF-12. Intraclass correlation coefficients were calculated for each summary component. The proportion of variability of the physical and mental summary components of the SF-36 (PCS-36 and MCS-36) explained by each component of the SF-12 was examined using a linear regression model, adjusted for age and gender. RESULTS: The mean scores observed were similar in the two questionnaires. The degree of agreement was high, and the corresponding regression model explained 87% of the variability in the PCS-36 and 93% of the variability in the MCS-36. The SF-12 identified the differences between AMI and angina in the same way as the SF-36. CONCLUSIONS: The SF-12 replicates the information of the summary component scores of the SF-36, and discriminates between patients with AMI and those with unstable angina. Its use allows the same information to be obtained as from the SF-36, with less effort for the patient and the doctor.

Outcomes and mutational analysis of patients with lower-risk non-del5q myelodysplastic syndrome treated with antithymocyte globulin with or without ciclosporine A.

Immunosuppressive treatment is a disease-modifying therapy for lower-risk myelodysplastic syndromes (MDS). However, IST is relatively rarely used and long-term outcomes of patients are seldom reported. We retrospectively studied outcomes of 20 patients with lower-risk non del 5q MDS with transfusion dependency, with horse or rabbit antithymocyte globulin ±â€¯ciclosporine A, and frontline eltrombopag in two of them. IPSS-R was low, intermediate and high in 30%, 55% and 10% of the patients, respectively. Fifty-five percent of the patients had hypocellular bone marrow (BM). Baseline mutations were detected in 31.5% of the patients and were more frequent in patients with normo/hypercellular MDS than in patients with hypocellular MDS. Transfusion independence rate for both red blood cells (RBC) and platelets was achieved in 45% of patients. RBC transfusion duration ≤6 months, B-cell counts >0.2 G/L and, marginally, BM blasts ≤2% were associated with higher transfusion independence rate. Age and cellularity did not influence the response rate. Median transfusion independence duration was 53 months. Cumulative incidence of progression to a more aggressive myeloid disease was 0 in patients without baseline mutations and 33% in patients with baseline mutations (P = .008). Median progression-free and overall survival after treatment onset and median overall survival after loss of transfusion independence were 45.5 months, 68 months and not reached, respectively. In conclusion, antithymocyte globulin ±â€¯ciclosporine A results in durable responses in MDS, irrespective of age, in patients with lower-risk disease without B-cell lymphopenia and treated early in the course of the disease.

Antibodies to native and denatured deoxyribonucleic acid in systemic lupus erythematosus.

The relative reactivities with native and denatured DNA of 35 lupus sera were investigated by quantitative complement fixation and precipitin studies and showed great variations. The use of purified native DNA demonstrated that, in at least 22 of these 35 sera, the anti-DNA antibodies reacted with the native form, independently of denatured contaminants. Systemic lupus sera were shown to contain three main types of DNA antibodies: those reacting only with denatured DNA, those reacting to the same extent with both forms of DNA, and those reacting preferentially with native DNA. In some instances, the latter antibodies fix complement and precipitate only with native DNA but are inhibited by the denatured form. This finding points to the importance of conformation in the antigenic structure of DNA. The simultaneous occurrence of different varieties of DNA antibodies was demonstrated in several sera. Evidence was obtained that some of these human antibodies to DNA can belong to the IgM class. Thus, DNA antibodies from systemic lupus patients differ in many respects from most of the experimentally produced antibodies capable of reacting with DNA.

Effect of chagasic sera on the rat isolated atrial preparation: immunological, morphological and function aspects.

An antibody reacting with the plasma membrane of working myocardial cells, skeletal muscle fibres, and endothelial cells (EVI antibody) has been described in the sera of patients with Chagas' disease. In the present study of rat isolated atrial preparations beating in ddifferent media, direct immunofluorescence and ultrastructural immunohistochemical procedures indicate that the antibody can interact with the living tissue, becoming fixed to the plasma membranes. Transmission electronmicroscopy studies also showed the presence of sarcolemmal alterations. These observations suggest a possible pathogenic effect of the EVI antibody. The presence of EVI-positive sera in the beating medium leads to a significant increase in the frequency of contractions; no significant effects of EVI-positive sera in contractile force were seen. The increase in frequency could be prevented by previous treatment with a b-adrenergic blocking agent (MJ-1999), but not by an x-blocker (phentolamine) or by an anti-histamine compound (cyproheptadine). The changes described were observed only in those atrial preparations which were beating in media containing EVI-positive sera. In those atria beating in control media (KR,KR plus normal human serum, KR plus EVI-negative chagasic serum), neither immunological nor morphological or functional changes wersence of EVI-positive chagasic serum diminished atrial stimulation after added norepinephrine. These results suggest the possibility that the EVI antibody may act as a b-adrenergic agonist at the cell plasma membrane level. Such an effect might account for some of the clinical features of chronic Chagas' heart disease.

Autoantibodies against lacrimal gland M3 muscarinic acetylcholine receptors in patients with primary Sjögren's syndrome.

PURPOSE: The authors demonstrated that immunoglobulin G, present in the sera of patients with primary Sjögren syndrome (pSS), could recognize and activate muscarinic acetylcholine receptors (mAChRs) of rat exorbital acrimal gland. METHODS: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting, and radioligand binding and biologic assays were used to demonstrate autoantibodies against mAChRs. RESULTS: These autoantibodies recognized by means of SDS-PAGE and immunoblotting assay a band of approximately 70 kDa expressed on lacrimal gland membranes that comigrated with the peak of labeled mAChRs. Moreover, pSS IgG were able to inhibit, in an irreversible manner, the binding of [3H]quinuclidinyl benzilate to mAChRs of rat exorbital lacrimal glands and to simulate the biologic effect of mAChR agonists, because they trigger the activation of phosphoinositide turnover. Atropine and 4-diphenylacetoxy-N-methylpiperidine methiodide blocked the effect and carbachol mimicked it, confirming that the M3 subtype mAChRs mediated pSS IgG action. As control, IgG from sera of women without pSS gave negative results on immunoblotting, binding, and biologic assays, thus demonstrating the specificity of the reaction. CONCLUSIONS: Autoantibodies against mAChRs may be considered among the serum factors implicated in the pathophysiology of the development of pSS dry eyes.

Modification of sarcolemmal enzymes by chagasic IgG and its effect on cardiac contractility.

It has been shown that sera from chagasic patients contain an antibody which binds to beta-adrenoceptors of myocardium and modulates their activity. Chagasic IgG triggered a marked stimulation of myocardial contractility with an increase in intramyocardial cyclic AMP and inhibition of (Na+ + K+)-ATPase activity. Both the mechanical and enzymatic effects of the IgG could be prevented by beta-adrenoceptor blockade or after the absorption of chagasic IgG with turkey red blood cells. In contrast, guinea pig red blood cells were unable to remove the beta-reactivity of chagasic IgG. These findings suggest that the IgG from chagasic patients increases myocardial contractility by behaving as a beta-agonist. This effect is likely related to stimulation of the adenylate cyclase coupled to the cardiac beta-adrenoceptor.

Immunofluorescent vascular pattern due to EVI antibody of Chagas' disease. Its diagnostic value.

One hundred fifty-six of 1,250 sera from patients with presumed connective tissue and related diseases showed vascular staining on mouse liver cryostat sections when they were routinely checked for antinuclear factor by the indirect immunofluorescence test. In a third of the cases, the vascular immunofluorescent pattern was given by the EVI antibody reacting with the plasma membrane of striated muscle fibers and endothelial cells, as has been recently described to occur in Chagas' disease. This led to the detection of previously unsuspected Trypanosoma cruzi infection in 67.8% of the serum samples in which the EVI antibody was detected after observation of a positive vascular pattern with mouse liver cryostat sections. On the other hand, no significant relationship between Chagas infection and sera with other anti-striated-muscle immunofluorescent patterns that also showed a vascular staining on mouse liver cryostat sections was established. Consideration of the vascular pattern observed with the EVI antibody on mouse liver cryostat sections can be helpful in detection of previously ignored T. cruzi infection in patients who have connective-tissue diseases and related conditions. This is of interest in view of the fact that anergic immunodepressive therapy, often used in these patients, significantly alters the host-parasite relationship and may lead to severe dissemination of the parasite.

Investigation of the EVI antibody in parasitic diseases other than American trypanosomiasis. An anti-skeletal muscle antibody in leishmaniasis.

The specificity of a circulating antibody observed in American trypanosomiasis and reacting with endocardium, blood vessels, and the interstitium of striated muscle (EVI factor) was evaluated in the indirect fluorescent antibody test with 60 sera from patients with malaria, leishmaniasis, echinococcosis, amebiasis, African trypanosomiasis, toxoplasmosis, and trichinosis, collected from areas where Chagas' disease is not endemic. Two sera, 1 from a patient with Plasmodium falciparum malaria and 1 from a patient with a relapse pretreatment post kala-azar dermal leishmaniasis, were positive for the EVI factor. In the leishmaniasis group, 3 of 8 sera reacted with 0ovine, murine, and human skeletal muscle. In this reaction, which differs from the EVI test, the sarcolemma and the intracellular structures were stained.

Chagasic sera alter the effects of ouabain on isolated rat atria. Participation of adrenergic mechanisms.

The effects of chagasic sera, containing an antibody (EVI antibody) which reacts with the plasma membrane of working myocardial cells, on "toxic" and "non-toxic" actions of ouabain upon isolated self beating or paced rat atria suspended in different media, were explored. Although ouabain produced a dose-dependent positive inotropic influence on atria suspended in Krebs-Ringer-bicarbonate (KRB) and in KRB plus normal human serum (KRB + NHS) it did not elicit any significant positive inotropic effect on atria beating in KRB plus EVI positive human chagasic serum (EVI(+)S). Additionally, EVI(+)S dose-response curves of classical signs of digitalis cardiac toxicity shifted to the left. The threshold concentration of ouabain required to elicit the onset of "toxic" effects was higher in control preparations (kept in KRB or KRB + NHS) than in EVI(+)S exposed preparations. (-)-Propranolol attenuated the overall toxic action of ouabain in EVI(+)S and facilitated its positive inotropic influence. In control media, the beta-adrenoceptor blocker failed to modify either the "non-toxic" or the "toxic" effect of ouabain. On the other hand, with control atria, subthreshold exogenous norepinephrine inhibited the positive inotropism of ouabain. The data suggest that an adrenergic mechanism is involved in the action of ouabain on cardiac tissue immersed in an EVI(+)S-containing solution. The foregoing results may explain the severe "toxic" effects observed with cardioactive glycosides when they are used in patients with Chagas' heart disease, even at low doses.

Cryostat sections with tissue amastigotes of Trypanosoma cruzi as a substrate for Chagas' disease serology.

Sera from 30 chronic chagasic patients together with 52 control samples (34 with other pathological conditions and 18 from normal individuals) were titrated by the indirect immunofluorescent technique (IFA) on Trypanosoma cruzi amastigotes. Acetone-fixed cryostat sections of skeletal muscle of Rockland mice 10 days post-infection with the RA isolate of T. cruzi were used as substrate. Results were compared with titres obtained by conventional IFA on epimastigotes. All 52 control sera had amastigote titres less than or equal to 2 double dilutions (dd) as compared with epimastigote values. Out of the 30 chagasic samples, differences were greater than or equal to 4 dd (less than or equal to 1 log) for 22, 3 dd for 5 and less than or equal to 2 dd for the remaining 3, when comparing amastigote and epimastigote titres. These results show that the use of amastigotes in cryostat sections of infected tissue for performing Chagas' serology in a simple, adequate and sensitive method.

Lymphatic tissue in Argentine hemorrhagic fever. Pathologic features.

Spleen and lymph nodes from seven fatal cases of Argentine hemorrhagic fever were studied by light and electron microscopy and by immunofluorescent techniques. In addition, Junin virus infectivity was determined. Destruction of splenic white pulp and of lymph node cortex was observed. The ultrastructural study showed a characteristic cytopathic effect on the macrophages with presence of intracisternal virus-like particles and occasional virions budding from the plasma membrane. The immunofluorescent techniques indicated the presence of Junin virus antigenic determinants in the cytoplasm of macrophages in the examined organs. Junin virus titers were three times higher than in peripheral blood. These results suggest that lymphatic tissue is one of the main sites of viral replication and that the macrophages are the targets of Junin virus.

Fatal post-partum pulmonary vasculitis in systemic lupus erythematosus.

A patient with fatal acute pulmonary vasculitis complicating systemic lupus erythematosus (SLE) of ten years duration is described. The patient died seven days after an uneventful pregnancy and delivery. Pathologic examination demonstrated acute necrotizing changes as well as organized lesions in pulmonary arteries. Acute pulmonary arteritis is rare in SLE and may develop as one of the major complications of the disease in the potentially dangerous post-partum period.

[Primary cardiac hemangioma. A case report and review of the literature]. / Hemangioma cardíaco primario. Presentación de un caso y revisión de la literatura.

A 26-years-old woman, without symptoms, was diagnosed of cardiac tumor by means of two-dimensional echocardiography, magnetic resonance imaging and angiocardiography. The tumor was removed underwent open-heart operation and cardiopulmonary bypass. Histologic study was suggestive of a capillary hemangioma. We present our experience with this case and a review of the literature.

[Congenital aneurysm of the sinus of Valsalva ruptured to right ventricle with a ventricular septal defect and aortic regurgitation]. / Aneurisma congénito del seno de Valsalva roto a ventrículo derecho, comunicación interventricular e insuficiencia aórtica.

We report the case of a patient with a congenital aneurysm of the sinus of Valsalva ruptured in the right ventricle, aortic valvular regurgitation and ventricular septal defect that remained asymptomatic for many years and presented clinically with severe volume overload of the heart and congestive heart failure. We describe the anatomic, echocardiographic and angiographic findings of this unusual entity with a review of the literature.

[Churg-Strauss syndrome with pericardial and myocardial involvement]. / Síndrome de Churg-Strauss con afectación pericárdica y miocárdica.

We report the case of a 63-year-old female diagnosed with Churg-Strauss syndrome with both pericardial tamponade and myocardial involvement with congestive heart failure. Allergic granulomatosis and angiitis (Churg-Strauss syndrome) is classically characterized by hypereosinophilia and systemic necrotizing vasculitis of medium and small arteries in patients with previous allergic rhinitis or bronchial asthma. Subsequently the disease has been shown to be associated with cardiac involvement and is responsible for higher morbidity and mortality. The literature for Churg-Strauss syndrome of the heart is reviewed and recent advances in the clinical management of the disease according to appropriate therapeutic strategies are recommended.

[Cardiac papillary fibroelastoma. Different forms of the clinical presentation]. / Fibroelastoma papilar cardíaco. Diferentes formas de presentación clínica.

Papillary fibroelastoma is an uncommon cardiac tumor rarely diagnosed during life. Although most fibroelastomas are incidental findings at autopsy, a few cases have been associated with cardiac symptoms that include angina, arterial embolism and sudden death. We report the case of two patients, a 35-year-old male with an acute myocardial infarction and ventricular fibrillation and a 53-year-old asymptomatic female, with cardiac masses first detected by transthoracic echocardiography. A more detailed morphological study was provided by transesophageal echocardiography. After cardiac surgery, the anatomical study demonstrated that both tumors were papillary fibroelastomas. The literature concerning papillary fibroelastoma is reviewed.

[Acute endocarditis of the native aortic valve caused by Propionibacterium acnes]. / Endocarditis aguda sobre válvula aórtica nativa por Propionibacterium acnes.

Propionibacterium acnes is often considered to be a contaminant but it has also been found to be the principal pathogen in serious infections. P. acnes is a rare cause of infective endocarditis. It has been suggested that aortic root abscesses are caused by bacteria that are particularly virulent. The strongest risk factor for serious infections by this bacteria is the presence of foreign bodies. A case is presented in which endocarditis of a native aortic valve caused by P. acnes was associated with an aortic root abscess. Transesophageal echocardiography is particularly helpful in the diagnosis of this severe complication of infective endocarditis. The literature for P. acnes endocarditis is reviewed.

[A hydatid cyst in the vena cava inferior and right atrium with venous flow obstruction and pulmonary dissemination]. / Quiste hidatídico en vena cava inferior y aurícula derecha con obstrucción del flujo venoso y diseminación pulmonar.

We report the case of a 62-year-old female patient operated for a hepatic hydatid cyst that years later was found to have a hydatid cyst in the inferior vena cava and right atrium that was the source of disseminated pulmonary spread of the disease and occlusion of the inferior vena cava blood flow. Cardiac hydatid disease is very uncommon and is frequently associated with a poor prognosis. The literature for hydatid disease of the heart is reviewed and the clinical and echocardiographic relevant findings of this patient are discussed.

Prevalence of anti-cytomegalovirus antibodies in a children population of Buenos Aires.

The seroprevalence of anti-Cytomegalovirus antibodies in a selected children population was studied by an enzyme-immunoassay (ELISA) prepared in our laboratory. Sera from 207 children from middle socio-economic classes were studied. Children were divided into the following groups: Group 1: cord sera (n = 87); Group 2: children aged 13 months to 6 years (n = 54); Group 3: children aged 6-15 years (n = 66). Overall seroprevalence was 46.3%. The seropositivity and ELISA index titers for the three groups were, respectively: Group 1, 55%, mean = 2.16; Group 2, 90.7%, mean = 5.15; Group 3, 59%, mean = 2.49. Group 2 exhibited higher seropositivity (p < 0.0001) and higher index titers (p < 0.0001) than the other two groups. These results suggests that primoinfection with Cytomegalovirus in this population occurs in children aged 13 months to 6 years (Group 2). However, the high percentage (55%) of cord blood without anti-Cytomegalovirus antibodies suggests a risk for congenital infection or primary infection for those newborn who required blood transfusions or were fed with bank milk. Further studies are needed to determine the impact of Cytomegalovirus infections in populations from different socio-economic classes, in congenital infections, the prevalence of antibodies in blood banks and their frequency in immunocompromised patients.