Induced mitotic homologous recombination by the babesicide imidocarb dipropionate in Aspergillus nidulans diploid cells.

Imidocarb dipropionate (IMD) is a chemotherapeutic agent prescribed for the treatment and control of babesiosis; it is known to be a nucleic acid synthesis inhibitor. Although it is an effective babesicide, there are reports of persistent IMD residues retained at high levels in edible tissues of cattle, swine and sheep, raising concerns about potential effects on humans. Since the carcinogenic potential of a chemical compound can be assessed through its effect on the homologous recombination, we investigated whether IMD is recombinogenic in Aspergillus nidulans diploid cells and whether it is capable of inducing homozygosis in genes that were previously heterozygous. This analysis was done with a homozygotization assay applied to a heterozygous diploid strain of A. nidulans. IMD used at non-toxic concentrations (2.5 to 10.0 µM) was recombinogenic, demonstrated by homozygotization indices higher than 2.0 for diploid markers. A diploid homozygous for genetic markers from chromosomes I and II was also produced. Since DNA replication blockers that induce DNA strand breaks have been classified as potent inducers of homologous recombination, the recombinogenic potential of IMD may be due to induction of recombinational repair.

Genotoxicity (mitotic recombination) of the cancer chemotherapeutic agents cisplatin and cytosine arabinoside in Aspergillus nidulans.

Cisplatin (cis-diamminedichloroplatinum, cis-DDP) and cytosine arabinoside (ara-C) are anticancer drugs used in the treatment of human cancer. The two chemotherapeutic drugs were tested in current research for their recombinogenic potential in diploid cells of Aspergillus nidulans. Non-cytotoxic concentrations of ara-C (0.4 and 0.8 microM) and cis-DDP (1.5, 3.0 and 6.0 microM) were strong recombinagens in A. nidulans UT448//A757 diploid strain, which induced homozygosis of recessive genetic markers, previously present in heterozygous condition. Drugs significantly increased homozygosity index (HI) values for five nutritional genetic markers when compared with those determined in the absence of anticancer drugs. Since mitotic recombination is a mechanism leading to malignant growth through loss of heterozygosity at tumor-suppressor loci, ara-C and cis-DDP may be characterized as secondary promoters of malignant neoplasia in diagnosed cancer patients, after chemotherapy treatment.

Vegetative compatibility and parasexual segregation in Colletotrichum lindemuthianum, a fungal pathogen of the common bean.

The heterokaryotic and vegetative diploid phases of Colletotrichum lindemuthianum are described using nutritional and biochemical markers. Nitrate non-utilizing mutants (nit), derived from R2047, R89, R73, R65, and R23 isolates, were paired in all possible combinations to obtain heterokaryons. Although pairings R2047/R89, R2047/R73, R65/R73, and R73/R23 showed complete vegetative incompatibility, prototrophic heterokaryons were obtained from pairings R2047/R65, R2047/R23, R65/R89, R65/R23, R73/R89, R89/R23, R2047/R2047, R65/R65, R89/R89, R73/R73, and R23/R23. Heterokaryons gave rise to spontaneous mitotic segregants which carried markers corresponding to one or the other of the parental strains. Heterokaryons spontaneously produced prototrophic fast-growing sectors too, characterized as diploid segregants. Diploids would be expected to yield auxotrophic segregants following haploidization in basal medium or in the presence of benomyl. Parental haploid segregants were in fact recovered from diploid colonies growing in basal medium and basal medium containing the haploidizing agent. Although barriers to the formation of heterokaryons in some crosses were detected, the results demonstrate the occurrence of parasexuality among vegetative compatible mutants of C. lindemuthianum.

Late outcome of unsupported annuloplasty for rheumatic mitral regurgitation.

OBJECTIVES: The aim of this study was to evaluate medium- and long-term (range 4 months to 17 years) clinical results in a series of patients treated surgically by unsupported mitral annuloplasty. BACKGROUND: Mitral valve regurgitation has usually been treated by valve replacement or ring annuloplasty. A few series have reported plastic repair procedures without annular support or remodeling. Furthermore, in rheumatic lesions the results have been inferior to those in degenerative mitral insufficiency, and the majority of previous reports have provided information on short- or medium-term follow-up. METHODS: One hundred fifty-four patients were operated on (55 male [36%] and 99 female [64%]). The mean age +/- SD was 36 +/- 16 years (range 5 to 73). Associated lesions comprised 47 aortic and 21 tricuspid valve lesions and 2 atrial septal defects. Patients with concomitant mitral stenosis were not included. Preoperative functional class was I or II in 19% and III or IV in 81%. The cardiothoracic ratio was 0.61 +/- 0.10. All patients underwent an unsupported mitral annuloplasty procedure in which the mural portion of the annulus was reduced by applying two buttressed mattress sutures at the commissures without compromising the width of the septal leaflet. When necessary, additional chordal procedures were performed. No patients received ring or posterior annular support. RESULTS: The early mortality rate was 1.9% (three patients; one of the three died of myocardial failure and two of pulmonary thromboembolism). The late mortality rate was 5.8% (nine patients; three of the nine died of myocardial failure, one each of septicemia, pulmonary thromboembolism and sudden arrhythmic death and three of unknown causes). Twenty-eight patients (18.2%) were reoperated on because of mitral valve dysfunction and 2 (1.3%) because of prosthetic aortic valve dysfunction. A residual late systolic murmur was present in 48% of patients. Late complications were systemic thromboembolism in 5.8% (one third with an aortic valve prosthesis), infective endocarditis in 1.3% and pulmonary thromboembolism in 0.6%. Postoperative functional class was I or II in 84% and III or IV in 16%. Cardiothoracic ratio was 0.58 +/- 0.10. Actuarial probability of late survival was 79.5 +/- 5.3% at 10 years and 71.0 +/- 7.4% at 14 years. Event-free survival was 67.9 +/- 8.9% at 10 years and 56.1 +/- 11.7% at 14 years. CONCLUSIONS: Rheumatic mitral regurgitation can be effectively treated by annuloplasty without prosthetic annular support, with late results comparable to those obtained with more complicated procedures. This observation is particularly important for treatment of children and young adult patients.

Subannular aortic aneurysms in whites. Report of two cases and review of literature.

Subannular aortic aneurysms are a rare entity occurring predominantly in young black men. Five white patients have been reported who underwent surgical correction, but long-term survival occurred in only two. We report two white men, 36 and 45 years old, who survived aortic valve replacement and direct suture of subannular aneurysms, with no symptoms at 29 and 42 postoperative months.

Side-to-side carotid-subclavian anastomosis for interrupted aortic arch.

A simple technique is proposed for restoring aortic flow in an interrupted aortic arch simulating a type B interruption that does not require aortic cross-clamping, circulatory arrest, or the ligation of major aortic branches. Side-to-side anastomosis between the left carotid and subclavian arteries together with division of the ductus arteriosus and pulmonary artery banding proved effective for relieving aortic arch stricture in that location.

Surgical repair of ventricular aneurysms. Early results with Cooley's technique.

Using bovine pericardium instead of Dacron for grafting, we performed ventricular endoaneurysmorrhaphy (Cooley's technique) in 13 patients with postmyocardial infarction left ventricular aneurysm. Twelve patients were men and 1 was a woman; their ages ranged from 38 to 67 years (mean, 51.2 +/- 11.4 years). Eight patients had large anterolateral aneurysms, 4 had apical aneurysms, and 1 had a false inferior aneurysm. Postoperatively, the mean cardiac index increased from 2.07 +/- 0.50 to 3.09 +/- 0.99 L/min/m2 (p < 0.05), with a mean percentage increase of 50.17% +/- 37.03%. No patient required postoperative mechanical circulatory assistance, and pharmacologic support could be withdrawn soon after surgery. All patients had uncomplicated recoveries and were asymptomatic upon discharge, at a mean time of 9.0 +/- 2.3 days after surgery. We conclude that ventricular endoaneurysmorrhaphy provides excellent initial results, and we believe, through subjective analysis of ventriculograms, that the use of bovine pericardium for grafting produces better functional results than does the use of Dacron.

[Infection of polytetrafluorethylene prosthesis in modified Blalock-Taussig anastomosis]. / Infecção de prótese de politetrafluoretileno em anastomose de Blalock-Taussig modificada.

A 16 month-old baby submitted to systemic-pulmonary shunt with a polytetrafluorethylene prosthesis, who presented hyperthermia, radiologic signs of pulmonary opacifications and positive culture for staphylococcus aureus. Reoperation disclosed a prosthesis pseudoaneurysm, with disconnection of the anastomosis and evidences of infection. This complication has a low diagnostic rate and a high mortality and should always be suspected when signs of systemic infection become apparent in the postoperative period of polytetrafluorethylene systemic-pulmonary shunt.

[Hospital risk factors in subclavian-pulmonary anastomosis with polytetrafluoroethylene graft]. / Fatores de risco hospitalar na anastomose subclávia-pulmonar com enxerto de politetrafluoretileno.

PURPOSE: Identification of risk factors for mortality in subclavian-pulmonary anastomosis using polytetrafluorethylene (PTFE). PATIENT AND METHODS: Immediate surgical results (30 days) were analyzed in 180 cyanotic patients consecutively operated on from september 1979 to march 1989. RESULTS: The hospital mortality was 12.7% (23 patients) and age at surgery, low weight (less than 3 kg) and preoperative diagnosis were considered risk factors for mortality. Pulmonary artery diameter at echocardiography, date of surgery and diameter of the conduits were associated with increased risk, but this association lacked statistical significance. Sex and previous palliative surgery have not increased hospital mortality. CONCLUSION: We believe that identification of risk factors to PTFE conduit implant plays an important role in the preoperative management of those patients in order to obtain better results in this life saving procedure.

[Modified Cooley technique for surgical repair of left ventricular aneurysms]. / Técnica de Cooley modificada para a correção cirúrgica de aneurismas do ventrículo esquerdo.

PURPOSE: To evaluate early postoperative results of modified Cooley's technique of ventricular endoaneurysmorrhaphy. PATIENTS AND METHODS: Eight patients, seven males, with ages ranging 38.0 to 67.0 years (m = 51.2 +/- 11.4 years) and with postinfarction left ventricular aneurysms were submitted to surgical repair by a modified Cooley's technique of ventricular endoaneurysmorrhaphy. RESULTS: No postoperative complication occurred and all patients were discharged from the hospital asymptomatic on a mean time of 9.0 +/- 2.3 days after surgery. The mean cardiac index increased from 2.1 +/- 0.5 to 3.3 +/- 1.1 l/min (p less than 0.05) with a mean percentual increase of 53.0%. No patient required mechanical circulatory assistance after surgery and the pharmacological support could be interrupted soon. CONCLUSION: Ventricular endoaneurysmorrhaphy searchs to restore shape, contour and volume to the left ventricle and has shown excellent initial results.

[Use of implantable pacemaker in the treatment of paroxysmal supraventricular tachycardia refractory to pharmacologic therapy]. / Uso de marcapasso implantável no tratamento da taquicardia supraventricular paroxística refratária à terapêutica farmacológica.

PURPOSE: To evaluate the results with the use of an automatic antitachycardia pacemaker in patients with refractory paroxysmal supraventricular tachycardia. PATIENTS AND METHODS: Nine patients aged 32 to 63 years with symptoms from 2 to more than 40 years and prophylactic treatment with several antiarrhythmic drugs that had failed to control tachycardia. The frequency of attacks in the year before the implant was from 1 per month to 3 daily and 4 of patients required direct counter current cardioversion at least once. The electrophysiologic studies demonstrated atrioventricular (AV) nodal reentry in 6 and AV reentry utilizing an accessory AV connection in 4 patients (in one patient both mechanisms were present). The patients have been followed from 2 to 18 months. RESULTS: All patients experienced new episodes of the arrhythmia that were successfully terminated by the pacemaker. Two patients presented episodes of tachycardia not terminated by the pacemaker. These events were successfully treated by reprogramming the unit. The drug treatment was discontinued in 7 patients. CONCLUSION: The antitachycardia pacemaker proved to be an effective therapeutic tool in reentrant supraventricular tachycardia refractory to pharmacologic therapy.

[The use of a rate-responsive pacemaker after heart transplantation]. / Uso de marcapasso com resposta de freqüência após transplante cardíaco.

PURPOSE: The indications and the results of pacemaker implant following orthotopic cardiac transplantation. METHODS: Four patients implanted a cardiac pacemaker (PM) in the early post-operative period (PO) of orthotopic cardiac transplantation (from 10th to 16th PO day). The patients were 33 to 55 year-old and the indications to PM were supraventricular arrhythmia (atrial fibrillation or flutter) associated with atrioventricular block in three, and complete atrioventricular block in one patient. Previous to PM implant, patients were submitted to endomyocardial biopsy, which was normal in two patients, evidenced mild rejection in one and moderate rejection in the remaining. A ventricular rate responsive pacemaker was implanted in all patients, with sensors responsive to muscular activity in one patient, and to minute ventilation in three. RESULTS: One patient died in the 20th PO due to acute allograft rejection not controlled by immunosuppressive drugs. Three other patients had satisfactory evolution and the pacemakers were programmed during exercise testing, previous to hospital discharge. Recent evaluation revealed that these patients are in good clinical condition at the 6th, 14th and 24th PO months. Adequate pacemaker function was insured by exercise testing and ambulatory electrocardiographic recording. CONCLUSION: A ventricular rate responsive pacemaker represented a satisfactory mode of pacing, in patients with severe bradycardia, following heart transplantation.

[Late evaluation with spiral computed tomography of smooth bovine pericardium grafts]. / Avaliação tardia por tomografia computadorizada espiral de enxertos de pericárdio bovino liso como substitutos aórticos.

PURPOSE: To evaluate morphologically by spiral computed tomography (SCT) bovine pericardial grafts as aortic substitutes. METHODS: Ten patients were submitted to aortic graft evaluation with SCT. There were 8 ascending and 2 descending grafts. Examination was done after 2 to 7 years post operative. Ages ranged from 49 to 67 years, with 6 male and 4 female patients. All had implanted smooth surface naked pericardial grafts. RESULTS: Surgical result was good in all. Distal dissection persisted in some cases. One had a peri-graft hematoma, 5 had no structural changes and 4 presented mild graft dilatation. There were no graft calcification or pseudoaneurysm. CONCLUSION: Glutaraldehyde preserved naked smooth surface bovine pericardial aortic grafts present satisfactory structural aspect, as seen by SCT, at medium term follow-up. Mild dilatation may be seen in some cases.

[Reinfusion of shed blood after heart surgery]. / Reinfusão de sangue drenado em pós-operatório de cirurgia cardíaca.

PURPOSE: To asses effectivity of postoperative reinfusion of shed mediastinal blood in reduction of homologous transfusions at cardiac surgery and to study the possibility of side effects. METHODS: Fifteen patients submitted to cardiac surgery that had their shed mediastinal blood reinfused after surgery were compared to another group of 15 patients. The two groups were compared in relation to: volume of shed blood, number of units of blood used in postoperative period, culture of shed blood, postoperative complications, number of days of hospitalization, hematocrit at the end of hospitalization and mortality. RESULTS: The use of whole blood and packed blood cells decreased from 25 to 10 units with reinfusion of shed mediastinal blood (p < 0.01). Volume of shed blood, postoperative complications, period of hospitalization, hematocrit at the end of hospitalization and mortality were not different in both groups. Culture of shed blood, in 8 patients of control group and all patients of study group were negative. CONCLUSION: Reinfusion of shed mediastinal blood in postoperative of cardiac surgery proved to be very efficient in decreasing homologous blood transfusions. This procedure is also safe, with no additional risk to patients.

Unsupported valvuloplasty in children with congenital mitral valve anomalies. Late clinical results.

OBJECTIVE: To analyze late clinical evolution after surgical treatment of children, with reparative and reconstructive techniques without annular support. METHODS: We evaluated 21 patients operated upon between 1975 and 1998. Age 4.67+/-3.44 years; 47.6% girls; mitral insufficiency 57.1% (12 cases), stenosis 28.6% (6 cases), and double lesion 14.3% (3 cases). The perfusion 43.10+/-9.50 min, and ischemia time were 29.40+/-10.50 min. The average clinical follow-up in mitral insufficiency was 41.52+/-53.61 months. In the stenosis group (4 patients) was 46.39+/-32.02 months, and in the double lesion group (3 patients), 39.41+/-37.5 months. The echocardiographic follow-up was in mitral insufficiency 37.17+/-39.51 months, stenosis 42.61+/-30.59 months, and in the double lesion 39.41+/-37.51 months. RESULTS: Operative mortality was 9.5% (2 cases). No late deaths occurred. In the group with mitral insufficiency, 10 (83.3%) patients were asymptomatic (p=0.04). The majority with mild reflux (p=0.002). In the follow-up of the stenosis group, all were in functional class I (NYHA); and the mean transvalve gradient varied between 8 and 12 mmHg, average of 10.7 mmHg. In the double lesion group, 1 patient was reoperated at 43 months. No endocarditis or thromboembolism were reported. CONCLUSION: Mitral stenosis repair has worse late results, related to the valve abnormalities and associated lesions. The correction of mitral insufficiency without annular support showed good long-term results.

[Adequacy of of pacemakers responsive to the volume-minute ventilation rate in heart transplantation patients]. / Adequação de marcapasso com resposta de freqüência por volume-minuto respiratório em pacientes submetidos a transplante cardíaco.

PURPOSE: To evaluate in the late post-operative period (PO) the chronotropic response to exercise of patients submitted to orthotopic cardiac transplantation (CT) and the implant of a cardiac pacemaker (PM). METHODS: A rate response ventricular PM (VVI+R) which uses minute ventilation (MV) as a sensor was implanted in five patients in the early PO of CT due to chronotropic incompetence. The patients were 31 to 64 years old and the indication to implant of PM was low ventricular escape rhythm following atrial taquicardia/bradycardia (one case) or sinus bradycardia (4 cases). The study was performed by means of paired exercise tests using Naughton protocol in order to compare the heart rate in VVI (prefixed heart rate) and VVIR+MV (rate response) mode. The duration of the exercise was compared between the two modes of stimulation. RESULTS: In VVI mode the heart rate was significantly lower than in VVIR+MV mode for comparable periods of exercise (101 +/- 12 ppm vs 132 +/- 4 ppm; p < 0.05); in VVIR+MV mode the patients had a prolonged time of exercise as compared to VVI mode (15 +/- 7 min vs 12 +/- 7 min; NS). CONCLUSION: The MV rate response PM provided patients with satisfactory heart during exercise and may be an adequate option to patients submitted to CT who present chronotropic incompetence.

Results of the surgical treatment of chronic atrial fibrillation.

OBJECTIVE: Report clinical experience in surgical treatment of atrial fibrillation (AF) by Cox-maze procedure. METHODS: 61 patients underwent surgical treatment for AF. Two had primary AF and 59 AF secondary to heart disease (2 atrial septal defects, 57 mitral). Ages ranged from 20 to 74 years (mean = 49). There were 44 females (72%). The surgical technique employed was Cox 3 without cryoablation. The patients were follow-up in specific at patient clinics and underwent periodical ECG, exercise tests, echocardiogram and Holter monitoring. RESULTS: In-hospital mortality was 4.9% and late mortality 1.6%. A temporary pacemaker was used in 28 (46%) and a definitive in 7 patients (11.4%). On hospital discharge, AF remained in 17%; 63.9% had sinus rhythm, 6.9% atrial rhythm, 1.7% junctional rhythm, and 10.3% had pacemaker rhythm. In the last evaluation, AF was present in 19.5%; (70.5% sinus rhythm, 4% atrial rhythm, 2% atrial tachycardia, and 4% pacemaker rhythm). There was no report of thromboembolic episodes. Chronotropic response was considered adequate in 19%, intermediate in 29%, and inadequate in 42%. In Holter monitoring, the mean heart rate was 82 +/- 8 bpm, with a minimum of 57 +/- 7 bpm and maximum of 126 +/- 23 bpm, with supraventricular extrasystoles in 2.3 +/- 5.5% of the total heartbeats and ventricular extrasystoles in 0.8 +/- 0.5%. In the echocardiogram, the A wave was present in the left atrium in 87.5%. CONCLUSION: Maze procedure is effective and has acceptable surgical risk. Atrial or sinus rhythms remain stable with a small but remarkable frequency of atrial and ventricular arrhythmias. Left atrial contraction is present, although attenuated, as well as the chronotropic response to exercise.

Ventricular evoked response in patients with hypertrophic obstructive cardiomyopathy treated with DDD pacing.

OBJECTIVE: To assess the changes in ventricular evoked responses (VER) produced by the decrease in left ventricular outflow tract gradient (LVOTG) in patients with hypertrophic obstructive cardiomyopathy (HOCM) treated with dual-chamber (DDD) pacing. METHODS: A pulse generator Physios CTM (Biotronik, Germany) was implanted in 9 patients with severe drug-refractory HOCM. After implantation, the following conditions were assessed: 1) Baseline evaluation: different AV delay (ranging from 150 ms to 50 ms) were sequentially programmed during 5 to 10 minutes, and the LVOTG (as determined by Doppler echocardiography) and VER recorded; 2) standard evaluation, when the best AV delay (resulting in the lowest LVOTG) programmed at the initial evaluation was maintained so that its effect on VER and LVOTG could be assessed during each chronic pacing evaluation. RESULTS: LVOTG decreased after DDD pacing, with a mean value of 59 +/- 24 mmHg after dual chamber pacemaker, which was significantly less than the gradient before pacing (98 + 22 mmHg). An AV delay > 100 ms produced a significantly lower decrease in VER depolarization duration (VERDD) when compared to an AV delay < or = 100 ms. Linear regression analyses showed a significant correlation between the LVOTG values and the magnitude of VER (r = 0.69; p < 0.05) in the 9 studied patients. CONCLUSION: The telemetry obtained intramyocardial electrogram is a sensitive means to assess left ventricular dynamics in patients with HOCM treated with DDD pacing.

Identification of Aspergillus flavus isolates as potential biocontrol agents of aflatoxin contamination in crops.

Aspergillus flavus, a haploid organism found worldwide in a variety of crops, including maize, cottonseed, almond, pistachio, and peanut, causes substantial and recurrent worldwide economic liabilities. This filamentous fungus produces aflatoxins (AFLs) B1 and B2, which are among the most carcinogenic compounds from nature, acutely hepatotoxic and immunosuppressive. Recent efforts to reduce AFL contamination in crops have focused on the use of nonaflatoxigenic A. flavus strains as biological control agents. Such agents are applied to soil to competitively exclude native AFL strains from crops and thereby reduce AFL contamination. Because the possibility of genetic recombination in A. flavus could influence the stability of biocontrol strains with the production of novel AFL phenotypes, this article assesses the diversity of vegetative compatibility reactions in isolates of A. flavus to identify heterokaryon self-incompatible (HSI) strains among nonaflatoxigenic isolates, which would be used as biological controls of AFL contamination in crops. Nitrate nonutilizing (nit) mutants were recovered from 25 A. flavus isolates, and based on vegetative complementation between nit mutants and on the microscopic examination of the number of hyphal fusions, five nonaflatoxigenic (6, 7, 9 to 11) and two nontoxigenic (8 and 12) isolates of A. flavus were phenotypically characterized as HSI. Because the number of hyphal fusions is reduced in HSI strains, impairing both heterokaryon formation and the genetic exchanges with aflatoxigenic strains, the HSI isolates characterized here, especially isolates 8 and 12, are potential agents for reducing AFL contamination in crops.