Aortopulmonary window. Clinical and surgical assessment of 18 cases

OBJECTIVE: Aortopulmonary window (APW) is an uncommon congenital malformation. Its clinical presentation is dependent on the size of the defect and on the associated lesions. We evaluated our experience with this anomaly and compared it with 296 cases reported in the literature. METHODS: Retrospective study of 18 patients diagnosed as having APW (age range from 13 days to 31 years, 13 (72.2%) females), divided into two groups: Group A (GA): 10 patients with isolated APW, and Group B (GB): 8 patients with associated lesions. RESULTS: Heart failure occurred in 14 patients, and cyanosis in 3: 2 from GB (tetralogy of Fallot - TF, and double outlet right ventricle - DORV), and one from GA with pulmonary hypertension. In 5 patients from GA the diagnosis of mitral regurgitation was made based on a systolic murmur and LV hypertrophy on the EKG. In GB, clinical findings were determined by the associated defect. Diagnosis was established by echocardiography in 11 (61.2%) of the patients. In 3 patients, a wrong diagnosis of mitral regurgitation was made, in 1 a patent ductus arteriosus was diagnosed and in 3 others, the diagnosis of APW was masked by other important associated defects (2 cases of DORV and 1 case of TF). The diagnosis was made by catheterization in 3 (16.6%) patients, by surgery in 3 (16.6%) and by necropsy in 1 (5.5%). Corrective surgery was performed in 14 (77.7%) patients, with one immediate death and good long-term follow-up in the remaining patients. CONCLUSION: APW can be confused with other defects. Clinical findings, associated with an adequate echocardiogram can provide the information for the correct diagnosis.

Study of Coronary Sinus Flow Reserve Through Transesophageal Doppler Echocardiography in Normal Subjects

OBJECTIVE - To evaluate the Coronary Flow Reserve in the Coronary Sinus through transesophageal Doppler echocardiography in normal subjects. METHODS - We obtained technically adequate flow samples for analysis in 10 healthy volunteers (37±8 years, 5 men) with no history of heart or systemic disease and with mean left ventricular mass index by transthoracic echocardiography of 87±18 g/m². Coronary sinus flow velocity was recorded within the coronary sinus with the patient in a resting condition and during intravenous adenosine infusion at a dose of 140 µg/kg/min for 4 minutes. Recording of coronary sinus blood flow was possible in all cases with measurement of peak systolic, diastolic, and retrograde velocities (PSV, PDV, and PRV, cm/sec), mean systolic and diastolic velocities (MSV and MDV, cm/sec), and systolic and diastolic velocity time integral (VTI S and VTI D, cm/sec). RESULTS - The coronary flow reserve was calculated as the ratio between the blood flow in the basal state and the maximum measured hyperemic blood flow with adenosine infusion. Results are shown as mean and standard deviations. (CFR = PSV + PDV -- PRV/basal PSV): 1st min = 2.2±0.21; 2nd min = 3±0.3; 3rd min = 3.4±0.37; 4th min = 3.6 ± 0.33. CONCLUSION - Although coronary sinus flow had significantly increased in the first minute, higher velocities were seen at third and fourth minutes, indicating that these should be the best times to study coronary sinus flow with intravenous adenosine in continuous infusion.

Morphometric and topographic study of coronary ostia

OBJECTIVE: To investigate the morphometric and topographic aspects of coronary ostia, correlating them with the aortic leaflets. METHODS: Fifty-one hearts with the great vessels attached were analyzed in this study. The ascending aorta was transversally sectioned 1 cm above the commissures of the aortic leaflets. The right and left coronary ostia were analyzed, as were the distances from these ostia to the bottom of the aortic sinuses and to the commissures of the aortic leaflets. RESULTS: The left coronary ostium was located below the intercommissural line in 42% of cases, above that line in 40% of cases, and at the level of that line in 18% of cases. The mean distance from the left coronary ostium to the bottom of the corresponding sinus was 12.6±2.61 mm. The right coronary ostium was located below the intercommissural line in 60% of cases, above that line in 28% of cases, and at the level of that line in 12% of cases. The mean distance from the right coronary ostium to the bottom of the corresponding aortic sinus was 13.2±2.64 mm. The mean diameters of the left and right coronary ostia were 4.75±0.93 mm and 3.46±0.94 mm, respectively. The mean diameters of the juxtamural portion of the left and right coronary arteries were 3.75±0.79 mm and 2.9±0.73 mm, respectively. In one case, both ostia were located in the left coronary sinus. CONCLUSION: The left coronary ostium may be located either above or below the intercommissural line. The right coronary ostium is predominantly located below the intercommissural line. The coronary ostia have reduced diameters as compared with the juxtamural diameters of their respective coronary arteries.

A study of aspects of heterokaryosis in aspergillus nidulans

A series of studies have been undertaken to find cases in which heterokaryons show adaptative response to environmental change. Comparisons have also been made between the phenotypes of heterokaryons and corresponding heterozygotes. Unsuccessful attempts were made to produce heterokaryons, on complete medium, balanced by one previously-existing mutant and one newly-obtained slow-growing mutant. Adaptation was achieved in heterokaryons carrying different mutant alleles conferring resistance to: (a) acriflavine, (b) actidione and (c) p-fluorophenylalanine. Comparison with the heterozygote in case (a) suggested a highly localised action of the allele determining resistance. A similar comparison for (b) suggested a non-localised action. In cases (b) and (c) dosage effects were observed in the degree of resistance that the heterokaryons, compared with the corresponding heterozygotes, could achieve. In case (c) interaction of the resistance marker with a nutritional marker (nic8) has been investigated further and a new unteraction between nic8 and Act1 detected. During this work a new conidial colour mutant, fawn, was isolated and characterised. It is likely to be a valuable visual marker, especially in view of its interaction with other colour mutants.

Study of an outbreak of cutaneous leishmaniasis in Venezuela: the role of domestic animals

During an outbreak of cutaneous leishmaniasis in a locality (Las Rosas, Cojedes State, venezuela) previously non-endemic, 12.9% of humans, 7% of dogs and 21.4% of donkeys (Equus asinus) had lesions with paraites. The agent in the three hosts was identified as Leishmania braziliensis, subspecies braziliensis at least in man and donkey. The probable vector was Lutzomyia panamensis. No infection was found in a small sample of wild mammals examined. The outbreak was apparently linked with the importation of donkeys with ulcers, from endemic areas. The Authors call attention to the fact that not only in the foci of "uta", but also in areas of the other forms of American cutaneous leishmaniasis, dogs are frequently found infected. They emphasize the necessity of searching for the infection in donkeys and of performing hemocultures and xenodiagnosis with sandflies in human, canine and equine cases, to verify their possible role as sources of infection, and not merely as dead ends in the epidemiological chain of the disease.

Virological study of a dengue type 1 epidemic at Rio de Janeiro

A dengue outbreak started in March, 1986 in Rio de Janeiro and spread very rapidly to other parts of the country. The great majority of cases presented classical dengue fever but there was one fatal case, confirmed by virus isolation. Dengue type 1 strains were isolated from patients and vectors (Aedes aegypti) in the area by cultivation in A. albopictus C6/36 cell line. The cytopathic effect (CPE) was studied by electron microscopy. An IgM capture test (MAC-ELISA) was applied with clear and reproducible results for diagnosis and evaluation of virus circulation; IgM antibodies appeared soon after start of clinical disease, and persisted for about 90 days in most patients. The test was type-specific in about 50% of the patients but high levels of heterologous response for type 3 were observed. An overall isolation rate of 46,8% (813 virus strains out of 1734 specimens) was recorded. The IgM test increased the number of confirmed cases to 58,2% (1479 out of 2451 suspected cases). The importance of laboratory diagnosis in all regions where the vectors are present is emphasized.

Neo/adjuvant chemotherapy does not improve outcome in resected primary synovial sarcoma: a study of the French Sarcoma Group.

BACKGROUND: There are only scarce data about the benefit of adjunctive chemotherapy in patients with localized synovial sarcoma (SS). PATIENTS AND METHODS: Data from 237 SS patients recorded in the database of the French Sarcoma Group were retrospectively analyzed. The respective impact of radiotherapy, neo-adjuvant chemotherapy and adjuvant chemotherapy on overall survival (OS), local recurrence-free survival (LRFS) and distant recurrence-free survival (DRFS) were assessed after adjustment to prognostic factors. RESULTS: The median follow-up was 58 months (range 1-321). Adjuvant, neo-adjuvant chemotherapy and postoperative radiotherapy were administered in 112, 45 and 181 cases, respectively. In all, 59% of patients treated with chemotherapy received an ifosfamide-containing regimen. The 5-year OS, LRFS and DRFS rates were 64.0%, 70% and 57%, respectively. On multivariate analysis, age >35 years old, grade 3 and not-R0 margins were highly significant independent predictors of worse OS. After adjustment to prognostic factors, radiotherapy significantly improved LRFS but not DRFS or OS. Neither neo-adjuvant nor adjuvant chemotherapy had significant impact on OS, LRFS or DRFS. CONCLUSION: As for other high-grade soft-tissue sarcomas, well-planned wide surgical excision with adjuvant radiotherapy remains the cornerstone of treatment for SS. Neo-adjuvant or adjuvant chemotherapy should not be delivered outside a clinical trial setting.

Spontaneous subconjunctival orbital fat prolapse: presentation of four cases

BACKGROUND: Subconjunctival orbital fat prolapse is a benign entity characterized by orbital fat herniation through a dehiscence in Tenon's capsule, usually between the superior and lateral recti muscles. It is often associated with ocular trauma or surgery, although spontaneous cases have also been reported with a predilection for obese individuals. PATIENTS AND METHODS: A retrospective study of four subconjunctival orbital-fat prolapse cases with no history of ocular surgery or trauma was performed. A trans-conjunctival surgical approach with Tenon's capsule repair was offered to all subjects. Differential diagnosis is discussed. RESULTS: The diagnosis of subconjunctival orbital fat prolapse was confirmed in all cases by histopathological examination. Functional and aesthetic postoperative results were excellent, with no recurrences during follow-up, for all cases. CONCLUSIONS: Although rare, subconjunctival orbital fat prolapse should be recognized. Surgical management offers excellent results.

A web-based pilot study of inter-pathologist reproducibility using the ISHLT 2004 working formulation for biopsy diagnosis of cardiac allograft rejection: The European experience.

BACKGROUND: The aim of this study was to assess, at the European level and using digital technology, the inter-pathologist reproducibility of the ISHLT 2004 system and to compare it with the 1990 system We also assessed the reproducibility of the morphologic criteria for diagnosis of antibody-mediated rejection detailed in the 2004 grading system. METHODS: The hematoxylin-eosin-stained sections of 20 sets of endomyocardial biopsies were pre-selected and graded by two pathologists (A.A. and M.B.) and digitized using a telepathology digital pathology system (Aperio ImageScope System; for details refer to http://aperio.com/). Their diagnoses were considered the index diagnoses, which covered all grades of acute cellular rejection (ACR), early ischemic lesions, Quilty lesions, late ischemic lesions and (in the 2005 system) antibody-mediated rejection (AMR). Eighteen pathologists from 16 heart transplant centers in 7 European countries participated in the study. Inter-observer reproducibility was assessed using Fleiss's kappa and Krippendorff's alpha statistics. RESULTS: The combined kappa value of all grades diagnosed by all 18 pathologists was 0.31 for the 1990 grading system and 0.39 for the 2005 grading system, with alpha statistics at 0.57 and 0.55, respectively. Kappa values by grade for 1990/2005, respectively, were: 0 = 0.52/0.51; 1A/1R = 0.24/0.36; 1B = 0.15; 2 = 0.13; 3A/2R = 0.29/0.29; 3B/3R = 0.13/0.23; and 4 = 0.18. For the 2 cases of AMR, 6 of 18 pathologists correctly suspected AMR on the hematoxylin-eosin slides, whereas, in each of 17 of the 18 AMR-negative cases a small percentage of pathologists (range 5% to 33%) overinterpreted the findings as suggestive for AMR. CONCLUSIONS: Reproducibility studies of cardiac biopsies by pathologists in different centers at the international level were feasible using digitized slides rather than conventional histology glass slides. There was a small improvement in interobserver agreement between pathologists of different European centers when moving from the 1990 ISHLT classification to the "new" 2005 ISHLT classification. Morphologic suspicion of AMR in the 2004 system on hematoxylin-eosin-stained slides only was poor, highlighting the need for better standardization of morphologic criteria for AMR. Ongoing educational programs are needed to ensure standardization of diagnosis of both acute cellular and antibody-mediated rejection.

Histopathological study of experimental and natural infections by Trypanosoma cruzi in Didelphis marsupialis

Didelphis marsupialis, the most important sylvatic reservoir of Trypanosoma cruzi, can also maintain in their anal scent glands the multiplicative forms only described in the intestinal tract of triatomine bugs. A study of 21 experimentally and 10 naturally infected opossums with T. cruzi was undertaken in order to establish the histopathological pattern under different conditions. Our results showed that the inflammation was predominantly lymphomacrophagic and more severe in the naturally infected animals but never as intense as those described in Chagas' disease or in other animal models. The parasitism in both groups was always mild with very scarce amastigote nests in the tissues. In the experimentally infected animals, the inflammation was directly related to the presence of amastigotes nests. Four 24 days-old animals, still in embryonic stage, showed multiple amastigotes nests and moderate inflammatory reactions, but even so they survived longer and presented less severe lesions than experimentally infected adult mice. Parasites were found in smooth, cardiac and/or predominantly striated muscles, as well as in nerve cells. Differing from the experimentally infected opossums parasitism in the naturally infected animals predominated in the heart, esophagus and stomach. Parasitism of the scent glands did not affect the histopathological pattern observed in extraglandular tissues.

A genome-wide association study of early menopause and the combined impact of identified variants.

Early menopause (EM) affects up to 10% of the female population, reducing reproductive lifespan considerably. Currently, it constitutes the leading cause of infertility in the western world, affecting mainly those women who postpone their first pregnancy beyond the age of 30 years. The genetic aetiology of EM is largely unknown in the majority of cases. We have undertaken a meta-analysis of genome-wide association studies (GWASs) in 3493 EM cases and 13 598 controls from 10 independent studies. No novel genetic variants were discovered, but the 17 variants previously associated with normal age at natural menopause as a quantitative trait (QT) were also associated with EM and primary ovarian insufficiency (POI). Thus, EM has a genetic aetiology which overlaps variation in normal age at menopause and is at least partly explained by the additive effects of the same polygenic variants. The combined effect of the common variants captured by the single nucleotide polymorphism arrays was estimated to account for ∼30% of the variance in EM. The association between the combined 17 variants and the risk of EM was greater than the best validated non-genetic risk factor, smoking.

Study of Staphylococcus aureus pathogenic genes by transfer and expression in the less virulent organism Streptococcus gordonii.

Because Staphylococcus aureus strains contain multiple virulence factors, studying their pathogenic role by single-gene inactivation generated equivocal results. To circumvent this problem, we have expressed specific S. aureus genes in the less virulent organism Streptococcus gordonii and tested the recombinants for a gain of function both in vitro and in vivo. Clumping factor A (ClfA) and coagulase were investigated. Both gene products were expressed functionally and with similar kinetics during growth by streptococci and staphylococci. ClfA-positive S. gordonii was more adherent to platelet-fibrin clots mimicking cardiac vegetations in vitro and more infective in rats with experimental endocarditis (P < 0.05). Moreover, deleting clfA from clfA-positive streptococcal transformants restored both the low in vitro adherence and the low in vivo infectivity of the parent. Coagulase-positive transformants, on the other hand, were neither more adherent nor more infective than the parent. Furthermore, coagulase did not increase the pathogenicity of clfA-positive streptococci when both clfA and coa genes were simultaneously expressed in an artificial minioperon in streptococci. These results definitively attribute a role for ClfA, but not coagulase, in S. aureus endovascular infections. This gain-of-function strategy might help solve the role of individual factors in the complex the S. aureus-host relationship.

Immunofluorescence test on Schistosoma mansoni worm paraffin sections (IgM-IFT) for the study of schistosomiasis transmission in Campinas, São Paulo, Brazil

The detection of IgM antibodies for Schistosoma mansoni using gut-associated antigens (IgM-IFT) was compared to the parasitological Kato-Katz method for study of the transmission of schistosomiasis in an urban area in Campinas. About 400 schoolchildren whose ages ranged from 6 to 18 years, were observed for a period of two years. Blood samples on filter paper and fecal samples were collected, at intervals of six months. Serological (IgM-IFT) prevalence rates of 1.2%, 4.3%, 3.6%, 2.9% and 3.4% were obtained in five surveys carried out. S. mansoni eggs were detected in only one child out of the 225 children (0.4%) who were submitted to the Kato-Katz method (three slides for each fecal sample) in the 1st survey. Sixty eight children who submitted five blood samples, one for each survey, were found IFT negative throughout the study. No child was found to be IFT positive in all five surveys, and only four children showed IFT positive results in at least four surveys. Seroconversion from IFT negative to positive was observed from the 1st to the 2nd survey in six chidren, from the 2nd to the 3rd survey in three children, from the 3rd to the 4th survey in four children, and from the 4th to the 5th survey in two cases. However, confirmation of S. mansoni infection using the fecal examination was not possible in any of the cases. Also, in most of them the IFT result oscillated from negative to positive and vice versa. Our data implied that recent transmission of schistosomiasis in the study area was not possible.

A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A.

Human genetic variation contributes to differences in susceptibility to HIV-1 infection. To search for novel host resistance factors, we performed a genome-wide association study (GWAS) in hemophilia patients highly exposed to potentially contaminated factor VIII infusions. Individuals with hemophilia A and a documented history of factor VIII infusions before the introduction of viral inactivation procedures (1979-1984) were recruited from 36 hemophilia treatment centers (HTCs), and their genome-wide genetic variants were compared with those from matched HIV-infected individuals. Homozygous carriers of known CCR5 resistance mutations were excluded. Single nucleotide polymorphisms (SNPs) and inferred copy number variants (CNVs) were tested using logistic regression. In addition, we performed a pathway enrichment analysis, a heritability analysis, and a search for epistatic interactions with CCR5 Δ32 heterozygosity. A total of 560 HIV-uninfected cases were recruited: 36 (6.4%) were homozygous for CCR5 Δ32 or m303. After quality control and SNP imputation, we tested 1 081 435 SNPs and 3686 CNVs for association with HIV-1 serostatus in 431 cases and 765 HIV-infected controls. No SNP or CNV reached genome-wide significance. The additional analyses did not reveal any strong genetic effect. Highly exposed, yet uninfected hemophiliacs form an ideal study group to investigate host resistance factors. Using a genome-wide approach, we did not detect any significant associations between SNPs and HIV-1 susceptibility, indicating that common genetic variants of major effect are unlikely to explain the observed resistance phenotype in this population.

Solitary Fibrous Tumor. Imaging findings in a series of nine cases

Es presenta un estudi retrospectiu descrivint les característiques radiològiques en una sèrie de nou casos de tumor fibrós solitari que affecta partes toves. Aquests resultats es comparen amb els resultats d’anatomia patològica i amb l’evolució clínica dels pacients