Mechanical load induced by glass microspheres releases angiogenic factors from neonatal rat ventricular myocytes cultures and causes arrhythmias.

In the present study, we tested the hypothesis that similar to other mechanical loads, notably cyclic stretch (simulating pre-load), glass microspheres simulating afterload will stimulate the secretion of angiogenic factors. Hence, we employed glass microspheres (average diameter 15.7 microm, average mass 5.2 ng) as a new method for imposing mechanical load on neonatal rat ventricular myocytes (NRVM) in culture. The collagen-coated microspheres were spread over the cultures at an estimated density of 3000 microspheres/mm2, they adhered strongly to the myocytes, and acted as small weights carried by the cells during their contraction. NRVM were exposed to either glass microspheres or to cyclic stretch, and several key angiogenic factors were measured by RT-PCR. The major findings were: (1) In contrast to other mechanical loads, such as cyclic stretch, microspheres (at 24 hrs) did not cause hypertrophy. (2) Further, in contrast to cyclic stretch, glass microspheres did not affect Cx43 expression, or the conduction velocity measured by means of the Micro-Electrode-Array system. (3) At 24 hrs, glass microspheres caused arrhythmias, probably resulting from early afterdepolarizations. (4) Glass microspheres caused the release of angiogenic factors as indicated by an increase in mRNA levels of vascular endothelial growth factor (80%), angiopoietin-2 (60%), transforming growth factor-beta (40%) and basic fibroblast growth factor (15%); these effects were comparable to those of cyclic stretch. (5) As compared with control cultures, conditioned media from cultures exposed to microspheres increased endothelial cell migration by 15% (P<0.05) and endothelial cell tube formation by 120% (P<0.05), both common assays for angiogenesis. In conclusion, based on these findings we propose that loading cardiomyocytes with glass microspheres may serve as a new in vitro model for investigating the role of mechanical forces in angiogenesis and arrhythmias.

Testing agonist-induced platelet aggregation by the Impact-R [Cone and plate(let) analyzer (CPA)].

The Impact-R [Cone and plate(let) analyzer (CPA)] is useful to assess platelet adhesion in different diseases and to monitor antiplatelet therapy. The purpose of the present study was to adapt this system to test agonist-induced platelet aggregation. Blood samples were tested by light transmission platelet aggregometry (LTA), Impact-R regular test and Impact-R agonist-response test. In the latter, samples were pre-incubated for 1 min with an agonist leading to platelet activation, micro-aggregates formation and reduced adhesion. Impact-R regular test of ten healthy volunteers demonstrated platelet adhesion (surface coverage, SC) of 11.2 +/- 2.6% while LTA induced by ADP, ristocetin, epinephrine, collagen and arachidonic acid (AA) yielded maximal aggregation (81% to 93%). In the Impact-R agonist-response test, SC was reduced to 2.2 +/- 1.0%, 1.2 +/- 0.9%, 2.3 +/- 1.0%, 2.2 +/- 0.8% and 2.4 +/- 0.4%, respectively. Prostaglandin E(1) treatment weakened SC reduction in response to ADP and epinephrine (SC of 8.8 +/- 1.8% and 9.5 +/- 2.0%, respectively). Inhibition of P2Y(12) receptor with 2MeSAMP resulted in a dose-dependent decrease in maximal aggregation in the ADP-induced test, which inversely correlated to SC in the Impact-R ADP-response test. The Impact-R agonist-response tests detected aggregation defects in patients with storage pool disease, severe von Willebrand disease and epinephrine response deficiency, and may be useful to assess the effect of different agonists on platelet aggregation.

First visceral leishmaniasis focus in Argentina

An eight-year old boy from Posadas (27º 23'S, 55º 54'W) was diagnosed with visceral leishmaniasis (VL) during 2006. Lutzomyia longipalpis was discovered in the backyard of his house, while the spread of canine visceral leishmaniasis was confirmed in Posadas. This is the southernmost report of a VL transmission focus and the first in Argentina.

Variable bleeding manifestations characterize different types of surgery in patients with severe factor XI deficiency enabling parsimonious use of replacement therapy.

Surgery performed without blood component therapy in patients with severe factor XI deficiency can be accompanied by excessive bleeding in some but not all patients. In an attempt to minimize the use of blood derivatives, we carried out a retrospective analysis of bleeding complications in 120 patients with severe FXI deficiency (level of <1-15 U dL-1) who had undergone different types of surgical procedures without replacement therapy. Procedures at tissues exhibiting fibrinolytic activity were associated with bleeding in 49-67% of the patients, while procedures involving sites with no local fibrinolytic activity were associated with bleeding in 1.5-40%. The increased bleeding tendency at fibrinolytic site was significant (P=0.0015), but was unrelated to the genotype of the patients. Thus, parsimonious use of replacement therapy is possible in patients with severe FXI deficiency undergoing surgery predicting a decrease in the risks of volume overload, transfusion related acute lung injury, transmission of infectious diseases, thrombosis, allergic reactions and development of inhibitors to FXI.

Rare bleeding disorders.

Deficiencies of coagulation factors other than factor VIII and factor IX (afibrinogenemia, FII, FV, FV+FVIII, FVII, FX, FXI, FXIII) that cause bleeding disorders (RBDs) are inherited as autosomal recessive traits and are rare, with prevalences in the general population varying between 1 in 500,000 and 1 in 2 million for the homozygous forms. As a consequence of the rarity of these deficiencies, the type and severity of bleeding symptoms, the underlying molecular defects, and the actual management of bleeding episodes are not as well established as for hemophilia A and B. The study of the genetic basis of these disorders could represent an important tool for prevention through prenatal diagnosis. Treatment of patients with RBDs during bleeding episodes or surgery is a challenge because of the lack of experience and the paucity of data. For some deficiency factor concentrates are still non available and severe complications can occur. These complications can be minimized by assessment of risks of bleeding and thrombosis, use of haemostatic means other than blood components or no therapy at all. The RBDs pose a problem for guideline writers because there are no suitable clinical trials to supply good evidence for how these people are best treated. The lack of adequate information on clinical manifestations, treatment and genetic basis of RBDs could be improved by the collection of data in an International Database (http://www.rbdd.org), linkable to others previously published. This could be a useful tool to fill the gap between clinical data and clinical practice. This article reviews the genetic basis of RBDs, problems and complications of treatment, problems in the preparation of suitable guidelines for treatment and the future perspectives of the International Registry on RBDs.

Lepidopterismo por Hylesia nigricans ( Mariposa negra ). Investigacion y accion preventiva en Buenos Aires / Lepidopterism due to the butterfly Hylesia nigricans. Preventive research-intervention in Buenos Aires

En el barrio El Pato,municipio de Berazategui, provincia de Buenos Aires, se realizó una investigación-acción preventiva contra la “mariposa negra” Hilesia nigricans, luego del aumento de consultas espontâneas por dematitis inespecífica. La incidência, durante el verano del año 2001, se estimo mediante una encuesta semiestructurada. En noviembre de 2002, se roció con Bacillus thuringiensis el arbolado público, evaluándose su efecto insecticida en campo y en laboratorio. El impacto se estimó mediante una encuesta pos-intervención en marzo de 2002. La distribución por edad, signos clínicos, persistência (11 días) y estacionalidad de los casos ( enero-febrero) fue consistente con dermatitis por H . nigricans. La mortalidad de larvas a las 96 horas del rociado fue del 100%. Las tasas de incidencia de dermatitis antes y después de la intervención fueron de 10.3% y 1.8% respectivamente. La acción coordinada de agentes nacionales, provinciales y locales permitió identificar el problema, diseñar investigaciones operacionales, y aplicar una estratégia de control preventivo, transferible por sus mismos efectores a la comunidad.

New observations on factor XI deficiency.

Factor (F) XI is an injury-related bleeding tendency that commonly occurs when trauma involves tissues rich in fibronolytic activators. Severe FXI deficiency is defined when the activity of FXI in plasma is less than 15 U dL(-1). The disorder is inherited as an autosomal recessive trait manifesting in homozygotes or compound heterozygotes, and infrequently in heterozygotes. So far 53 mutations in the gene of FXI have been described and four of them were found to be prevalent in Ashkenazi Jews, Iraqi Jews, Basques or the English population. For each of the four mutations a founder effect was discerned. Inhibitors can develop in patients with FXI level < 1U dL(-1) who were exposed to plasma which seriously complicates their management during surgery. No correction of a prolonged aPTT by normal plasma is indicative of the presence of an inhibitor. In contrast to patients with haemophilia A, severe FXI deficiency provides no protection against myocardial infarction. In patients with severe FXI deficiency undergoing surgery, fresh frozen plasma is the treatment of choice. FXI concentrates can also be used but cause thrombosis in approximately 10% of patients, particularly those with cardiovascular disease. Recombinant FVIIa has successfully prevented bleeding during or after surgery in patients with FXI inhibitors.

Carotid artery inflow in operations to correct aortic diseases (ascending, arch and descending)

OBJETIVO: A canulaçäo da artéria femoral tem sido a via mais comum para o retorno arterial, nas operações para correçäo de aneurismas ou dissecções da aorta ascendente e ou arco aórtico. Mais recentemente, a artéria subclávia também tem sido usada. O objetivo deste trabalho é apresentar uma experiência inicial, com nove pacientes, em que se utilizou a artéria carótida comum direita para este retorno. MÉTODO: Operaram-se nove pacientes com idade de 46 - 80 anos (62,1± 12,54), seis eram do sexo masculino, quatro tinham aneurismas verdadeiros, três apresentavam dissecções e, em dois, havia combinaçäo de dissecçäo com aneurisma verdadeiro. Eram cinco reoperações. Em quatro pacientes (reoperações) a circulaçäo extracorpórea (CEC) foi estabelecida utilizando-se artéria carótida direita e a toracotomia foi feita quando a temperatura esofágica alcançou 20ºC, nesses casos a drenagem venosa foi realizada por uma das veias femorais. Nos demais pacientes, a CEC foi estabelecida entre a artéria carótida comum direita e o átrio direito. Em ambas situações a artéria carótida comum direita foi incisada e um tubo de PTFE foi anastomosado à arteriotomia, sendo a linha arterial conectada a este tubo. A temperatura dos pacientes variou de 15 a 30ºC, dependendo da extensäo da doença. O tempo de CEC variou de 80 a 198 min. (120,9±44,32). Em dois pacientes realizou-se parada circulatória, em sete pacientes utilizou-se hipofluxo (perfusäo cerebral anterógrada). RESULTADOS: Sete pacientes tiveram boa evoluçäo e dois faleceram, um por insuficiência respiratória no sétimo pós-operatório e outro por rotura de um aneurisma tóraco-abdominal no terceiro dia pós-operatório. Todos os nove pacientes acordaram sem qualquer seqüela neurológica. CONCLUSÕES: Nesta técnica pode-se estabelecer a CEC antes da toracotomia, o que é importante nas reoperações, permitindo manter perfusäo cerebral anterógrada com hipofluxo durante procedimento no arco aórtico.

Field trials of an improved cost-effective device for detecting peridomestic populations of Triatoma infestans (Hemiptera: Reduviidae) in rural Argentina

An improved device for detecting peridomestic Triatoma infestans consisting of one-liter recycled Tetra Brik milk boxes with a central structure was tested using a matched-pair study design in two rural areas in Argentina. In Olta (La Rioja), the boxes were installed beneath the thatched roofs and on the vertical wooden posts of each peridomestic structure. After a 5-month exposure, at least one of the recovered boxes detected 88 percent of the 24 T. infestans-positive sites, and 86 percent of the 7 negative sites by timed manual collections at baseline. In Amamá (Santiago del Estero), the boxes were paired with the best performing prototype tested before (shelter unit). After 3 months, some evidence of infestation was detected in 89 percent (boxes) and 79 percent (shelters) of 18-19 sites positive by timed collections, whereas 19 percent and 16 percent of 32 negative sites were positive, respectively. Neither device differed significantly in the qualitative or quantitative collection of every sign of infestation. The installation site did not modify significantly the boxes' sampling efficiency in both study areas. As the total cost of each box was half as expensive as each shelter unit, the boxes are thus the most cost-effective and easy-to-use tool for detecting peridomestic T. infestans currently available

Minimally invasive single-vessel coronary artery bypass with the internal thoracic artery and early postoperative angiography: midterm results of a prospective study in 120 consecutive patients.

BACKGROUND: This prospective study was undertaken to determine the role of the minimally invasive direct coronary artery bypass with early postoperative angiography and midterm follow-up in 120 consecutive patients with single-vessel coronary artery disease. METHODS: Minimal access (6 to 10 cm), without complete sternotomy and no cardiopulmonary bypass, was used. The lesions were located at the proximal left anterior descending coronary artery in 95% of the patients. Routine coronary angiography was performed before discharge. RESULTS: Postoperative angiography was performed in 104 (90.4%) of those 115 patients who had coronary revascularization concluded by the mini-access method. The internal thoracic artery patency rate was 98.1% (95.2% grade A). Two (1.7%) patients presented with perioperative myocardial infarction, which led to the single in-hospital death (0.8%). Of the remaining 119 patients, 113 (95.0%) were asymptomatic. The event-free probability was 94.9% and the actuarial survival was 98.3% with 42 months of follow-up. CONCLUSIONS: For selected patients with single-vessel coronary artery disease and no major myocardial dysfunction, minimally invasive direct coronary artery bypass is a safe operation and a less invasive alternative to conventional coronary artery bypass grafting.

Study of a cutaneous leishmaniasis outbreak in General Vedia, Province of Chaco, 1996

Between March and July 1996, a focalized epidemic outbreak of cutaneous leishmaniasis in General Vedia, province of Chaco, associated to the gallery forest of the Oro river was verified. The incidence rate in the area, which was 0-2/000 cases in preceding years, reached 8/000 cases in 1996. The risk of symptomatic infection was similar between sexes, but was different when analizing the different age groups by sex, suggesting a greater relative importance of the peridomestic transmission for the females and of the transmission in the subtropical forest for the males. Specimens of Lutzomyia intermedia, a species already incriminated as a vector of Leishmaniasis in other provinces of northern Argentina, were captured and identified in the focus locality in May 1996. The possible causes of the outbreak related to the climatic variables and the vector abundance are analyzed and the results in the framework of possible preventive and control activities are discussed

American cutaneous leishmaniasis outbreak, Tartagal city, province of Salta, Argentina, 1993

An American cutaneous leishmaniasis outbreak, with cases clustering during 1993 in Tartagal city, Salta, was reported. The outbreak involved 102 individuals, 43.1 percent of them with multiple ulcers. Age (mean: 33 years old) and sex distribution of cases (74.5 percent males), as well as working activity (70 forest-related), support the hypothesis of classical forest transmission leishmaniasis, despite the fact that the place of permanent residence was in periurban Tartagal. Moreover, during July, sandflies were only collected from one of the 'deforestation areas'. Lutzomyia intermedia was the single species of the 491 phlebotomines captured, reinforcing the vector incrimination of this species. Most infections must have been acquired during the fall (April to June), a pattern consistent with previous sandfly population dynamics data. Based on the epidemiological and entomological results, it was advised not to do any vector-targeted periurban control measures during July. Further studies should be done to assess if the high rate of multiple lesions was due to parasite factors or to infective vector density factors

Dinuclear diazene iron and ruthenium complexes as models for studying nitrogenase activity.

The strength of hydrogen bonds has been investigated in various dinuclear diazene FeII, FeIII, and RuII complexes by use of the recently developed shared-electron number approach. Hydrogen bonding in these compounds plays an essential role in view of designing a model system for nitrogenase activity. The general conclusions for iron-sulfur complexes are: hydrogen bonds can stabilize diazene by at least 20% of the total coordination energy; the strength of the hydrogen bonds can be directly controlled through the hydrogen-sulfur bond length; reducing FeIII centers to FeII can double the hydrogen bond energy.

[Control of the transmission of Trypanosoma cruzi in Argentina 1999]. / Control de la transmisón de Trypanosoma cruzi en la Argentina 1999. Grupo de Desarrollo y Aplicación Operativa.

Approximately 2 million people in Argentina are infected with Trypanosoma cruzi, the etiologic agent of Chagas disease, thereby constituting the major tropical disease in the country. As in other six Southern Cone countries, Triatoma infestans is the only or major vector of T. cruzi among human and domestic animals. In Argentina, a vertically structured National Chagas Control Program was established in 1962. Such a program pursued the elimination of domestic and peri-domestic populations of T. infestans through insecticidal spraying, and the serological control of blood donors to prevent transfusion-related infections. This program strongly reduced the nation-wide serological prevalence of T. cruzi in the population. For example, in 18 or 20 year-old men drafted into military service, the seroprevalence decreased from 10.1% in 1964 for those who had been born in 1944 to 1.9% in 1993 for those born in 1975. However, the vertical strategy failed to reach and sustain the surveillance phase in widespread rural areas with disperse populations due to its intrinsic limitations and the reduced priority level assigned to rural health programs. An alternative, horizontally-structured control strategy of T. infestans was developed and assayed in the Province of Santiago del Estero between 1985-1989, and 1991-1992. The projects demonstrated that insecticidal spraying carried out with community participation combined effectiveness and commitment in such a way as to produce a strong impact on house reinfestation and the extension of the area under entomological surveillance. This experience has been transferred in a chain of responsibilities to the personnel of the National Chagas Control Program, using participating workshops, procedural guidelines, and practical training. This personnel transferred the strategy using similar methods to the field health care agents and volunteers chosen by their own communities (community leaders). After the workshops, the leaders received all the materials needed to install and develop the ongoing surveillance activities: third generation pyrethroid insecticides, manuals, hand-operated sprayers, and sensor boxes to detect domiciliary infestations. From 1993 to 1998, a total of 15,000 health care agents or community leaders were trained. A total of 675,000 houses were sprayed with residual insecticides in the attack phase, and 850,000 houses entered the surveillance phase. This is the first time that such large coverage has been accomplished in Argentina. The network of laboratories installed a quality assurance program to current serological procedures applied to blood donors, organ transplant, and the detection and treatment of newborns to women sero-reactive for T. cruzi in Argentina. We expect to interrupt the vector-mediated transmission of T. cruzi in the next 18 months, but the sustainability of such a program depends on, at least, additional work with the community to achieve a change of attitudes and practices related to house infestation for the next 10 years. A social effort will be needed to cover those expenses, but the expected economic returns exceed largely the cost of any such program, as suggested by cost-benefit studies. To illustrate, the annual treatment costs of one Chagas patient can help maintain 25 households free from triatomine bugs in Argentina.

Aneurisma em ponte de veia safena para artéria coronária marginal esquerda, roto para o brônquio esquerdo / Aneurysm in the saphenous vein bypass graft to the left marginal coronary artery, broked up to the left bronchus

Paciente com duas cirurgias prévias de revascularizaçao do miocárdio há 20 e lO anos, respectivamente, apresentou subitamente quadro de dispnéia, dor torácica e hemoptise. Aos exames complementares, foi observado um grande aneurisma da ponte de veia safena para artéria marginal esquerda, parcialmente roto em brônquio esquerdo. O aneurisma foi corrigido, com sucesso, mas o paciente veio a falecer no l5( pós-operatório em conseqüência de uma infecçao pulmonar.

Growth pattern and clinical correlation of subcutaneously inoculated human primary acute leukemias in severe combined immunodeficiency mice.

We examined the ability of patient-derived human leukemic blasts to generate leukemic growth and dissemination in severe combined immunodeficiency (SCID) mice by subcutaneous inoculation without conditioning treatment or administration of growth-promoting cytokines. Additionally, we correlated the growth pattern with the clinical outcome of patients from whom the leukemic cells were derived. The leukemias displayed three distinct growth patterns, ie, either aggressive, indolent, or no tumor growth. Leukemic cells from 6 of 13 patients with acute myeloid leukemia (AML), 4 of 7 T-cell acute lymphoblastic leukemia (T-ALL), and 11 of 16 patients with B-lineage ALL grew as subcutaneous tumors, with a significant number subsequently disseminating into distant organs in SCID mice. Patients whose leukemic blasts displayed an aggressive growth and dissemination pattern in SCID mice had a relatively poor clinical outcome, whereas patients with AML and T- or B-lineage ALL whose leukemic blasts grew indolently or whose cells failed to induce growth had a more favorable clinical course. Our study has shown that the subcutaneous inoculation of patient-derived human leukemic cells in SCID mice can engraft and grow as subcutaneous tumors with subsequent dissemination to distant organs in a manner analogous to their pattern of growth in humans. Additionally, these data suggest a clinical correlation to the growth and dissemination of some leukemic subtypes that may represent not only an additional prognosticator for patient outcome, but also a vehicle for the study of the biologic behavior of human leukemias and the development of novel therapeutic strategies.

Revascularizaçäo miocárdica associada a endarterectomia da carótida / Combined coronary-carotid operations combined operattion for myocardial revascularization and carotid endarterectomy

A oportunidade para realizaçäo de endarterectomia de carótida(EC) e revascularizaçäo miocárdica(RM) para doença concomitantemente ainda é controversa. Entre 1979 e 1994, 10.940 pacientes foram operados para revascularizaçäo miocárdica. Cirurgia combinada RM/EC foi realizada em 46 pacientes (0,43 por cento) no mesmo período. A idade desses pacientes variou de 48 a 76 anos, média de 65,2 anos, sendo 34,7 por cento (16/46) com 70 anos ou mais; 80,4 por cento eram do sexo masculino. Infarto miocárdico prévio estava presente em 23 pacientes (50 por cento); diabetes mellitus em 10 pacientes (21,7 por cento); insuficiência renal crônica em cinco pacientes (10,8 por cento); 29 pacientes (63 por cento) estavam em classe funcional III ou IV para angina; havia ICC em 4 pacientes (8,6 por cento); havia lesäo obstrutiva significativa em 9 pacientes (19,5 por cento) no tronco da coronária esquerda; cinco pacientes estavam sendo reoperados para RM e um paciente para RM e EC. Dos pacientes com lesäo carotídea bilateral (25 pacientes), quatro tinham uma artéria carótida interna ocluída. Vinte e três pacientes tinham tido isquemia cerebral transitória (ICT) e dois pacientes, acidente vascular cerebral (AVC) com sequela permanente; 21 pacientes näo tinham manifestaçäo neurológica. EC foi realizada na carótida esquerda em 23 pacientes, na direita, em 14 e bilateral, em 9 pacientes. A RM foi realizada com pontes de safena e artétias torácicas internas(ATI), variando de 1 a 4 pontes, com média de 2,8 pontes por paciente; onze pacientes receberam ATI. A mortalidade imediata(hospitalar ou 30 dias) foi de 8,6 por cento (4/46). AVC permanente näo ocorreu no transoperatório. Três dos quatro óbitos ocorreram em pacientes com idade igual ou superior a 70 anos. A EC foi realizada após preparo e heparinizaçäo do paciente para circulaçäo extracorpórea (CEC). Nos quatro pacientes que apresentavam oclusäo da artéria carótida interna contralateral a EC foi realizada após o estabelecimento da CEC e com hipotermia sistêmica de 25 graus centígrados. Em nenhum caso foi utilizado ®shunt¼ carotídeo. Nos casos de lesöes cirúrgicas bilaterais, o lado com lesäo de risco maior foi operado com a RM, sendo a outra carótida operada em segundo tempo ( em torno de uma semana). Considerando que nenhum paciente apresentou AVC transoperatório, achamos ser a conduta adequada para associaçäo de lesöes