Search PubMed⌕ Search

Biomedical subjects

J A Gomes

Publications and source records attributed to J A Gomes.

At least 19 recordsLinked to original sources

Prediction of long-term outcomes by signal-averaged electrocardiography in patients with unsustained ventricular tachycardia, coronary artery disease, and left ventricular dysfunction.

BACKGROUND: An abnormal signal-averaged ECG (SAECG) is a noninvasive marker of the substrate of sustained ventricular tachycardia after myocardial infarction. We assessed its prognostic ability in patients with asymptomatic unsustained ventricular tachycardia, coronary artery disease, and left ventricular dysfunction. METHODS AND RESULTS: A blinded core laboratory analyzed SAECG tracings from 1925 patients in a multicenter trial. Cox proportional hazards modeling was used to examine individual and joint relations between SAECG variables and arrhythmic death or cardiac arrest (primary end point), cardiac death, and total mortality. We also assessed the prognostic utility of SAECG at different levels of ejection fraction (EF). A filtered QRS duration >114 ms (abnormal SAECG) independently predicted the primary end point and cardiac death, independent of clinical variables, cardioverter-defibrillator implantation, and antiarrhythmic drug therapy. With an abnormal SAECG, the 5-year rates of the primary end point (28% versus 17%, P=0.0001), cardiac death (37% versus 25%, P=0.0001), and total mortality (43% versus 35%, P=0.0001) were significantly higher. The combination of EF <30% and abnormal SAECG identified a particularly high-risk subset that constituted 21% of the total population. Thirty-six percent and 44% of patients with this combination succumbed to arrhythmic and cardiac death, respectively. CONCLUSIONS: SAECG is a powerful predictor of poor outcomes in this population. The noninvasive combination of an abnormal SAECG and reduced EF may have utility in selecting high-risk patients for intervention.

Coronary Disease↗

IL-4 and IL-13 regulate the induction of indoleamine 2,3-dioxygenase activity and the control of Toxoplasma gondii replication in human fibroblasts activated with IFN-gamma.

The ability of up-regulatory [recombinant (r) IFN-gamma, rIFN-beta and rTNF-alpha] and down-regulatory (rIL-4, rIL-10 and rIL-13) cytokines to control the expression of indoleamine 2,3-dioxygenase (INDO) and anti-Toxoplasma activity in the human fibrosarcoma cell line 2C4 was evaluated. Activation of fibroblasts with rIFN-gamma, rIFN-beta and rTNF-alpha resulted in augmentation of INDO expression and activity leading to 40.0, 25.0 and 27.0 % inhibition of tachyzoite growth, respectively. An additive effect was observed when host cells were incubated with rIFN-gamma plus rTNF-alpha. With regard to the down-regulatory cytokines we observed that IL-4 as well as IL-13, but not IL-10, induced significant inhibition of IFN-gamma-induced control of parasite replication, INDO mRNA expression and tryptophan catabolism. Similarly, IL-4 but not IL-10 inhibited the cell surface expression of HLA-DR and CD2 induced by IFN-gamma. Consistent with these findings we were able to detect by reverse transcription-PCR the expression of mRNA for different chains of IL-4 and IL-13 receptors (IL-4Ralpha, IL-13Ralpha1 and IL-13Ralpha2) but not for IL-10 receptor in the 2C4 and other human lung fibroblast cell lines (LL24 and MRC5). Together our results indicate that IL-4 and IL-13, but not IL-10, are implicated in the negative regulation of IFN-gamma-induced anti-Toxoplasma activity in human cells from fibroblast lineage.

Animals↗

The search for a new model structure of beta-factor XIIa.

We present the search for a new model of beta-factor XIIa, a blood coagulation enzyme, with an unknown experimental 3D-structure. We decided to build not one but three different models using different homologous proteins as well as different techniques and different modelers. Additional studies, including extensive molecular dynamics simulations on the solvated state, allowed us to draw several conclusions concerning homology modelling, in general, and beta-factor XIIa, in particular.

Amino Acid Sequence↗

Signal-averaged P-wave ECG discriminates between persistent and paroxysmal atrial fibrillation.

Atrial fibrillation (Afib) has been associated with abnormal signal-averaged P wave (SAPW) parameters but whether SAPW is associated with the time course of these arrhythmias (persistent vs. paroxysmal, frequent vs. rare episodes) remains unknown. This article assesses the significance of SAPW duration in distinguishing patients with paroxysmal from those with persistent Afib. SAPW electrocardiogram was performed with a "double triggering" software system for acquisition and analysis of data. SAPW total duration (TD), X, Y, and Z leads magnitudes and vector signal magnitudes were measured offline. Optimal cutoff value between control and patient groups was determined by using a receiver operator characteristic curve. Data were analyzed to compare controls with patients groups and between patient groups according to time course of the arrhythmic history. Fifteen age-matched patients without a history of Afib and 55 patients with a history of Afib (33 with paroxysmal and 22 with persistent arrhythmia) were studied off antiarrhythmic drugs. Patients with history of persistent arrhythmia were studied within 2 days after electrical cardioversion to sinus rhythm. SAPW TD was the only parameter consistently associated with Afib. SAPW TD was 98 +/- 6 ms (mean +/- SD) in the control group, 127 +/- 19 ms in the pooled patients group (P =.0001); 122 +/- 20 ms for paroxysmal and 133 +/- 17 ms for the persistent Afib group (P =.04). Analysis of other SAPW parameters were not statistically significant. SAPW duration is a simple method to identify patients with history of Afib. A significantly longer SAPW TD characterizes patients with a history of persistent as opposed to paroxysmal Afib. Prolongation of SAPW TD possibly reflects more advanced electrophysiological changes, creating a more stable substrate that leads to persistence of the arrhythmia.

Algorithms↗

Anterior stromal puncture in the treatment of bullous keratopathy: six-month follow-up.

PURPOSE: This study was designed to evaluate the effect of anterior stromal puncture to treat patients with symptomatic bullous keratopathy. METHODS: Fourteen patients with bullous keratopathy who had decreased vision and were or were not awaiting penetrating keratoplasty were evaluated before and 1, 4, 12, and 24 weeks after anterior stromal punctures with a 25-gauge needle. The patients were questioned about pain intensity, foreign-body sensation, and photophobia. Biomicroscopy, esthesiometry, and pachymetry results were evaluated. The results before and after the punctures were compared using the McNemar test, Friedman test, and multiple comparison tests. RESULTS: The comparisons among before and 1, 4, and 12 weeks after the anterior stromal puncture of pain (p = 0.00000556), photophobia (p = 0.0252), foreign-body sensation (p = 0.0000743), and esthesiometry (p = 0.0243) showed significant statistical differences in terms of decreasing symptoms and corneal sensitivity. The average pachymetry did not show statistical difference among before and 1, 4, 12, and 24 weeks after the procedure (p = 0.956). We did not find important differences in terms of corneal neovascularization. CONCLUSION: Anterior stromal puncture is an effective, simple, and low-cost alternative for treating patients with symptomatic bullous keratopathy.

Adult↗

Immunological and clinical evaluation of chagasic patients subjected to chemotherapy during the acute phase of Trypanosoma cruzi infection 14-30 years ago.

We recently evaluated the in vitro proliferative response and interferon (IFN)-gamma production of peripheral blood mononuclear cells from a group of 25 people who were treated for Chagas' disease during the acute phase of Trypanosoma cruzi infection and followed up for a period of 14-30 years. On the basis of the parasitological and serological tests, the individuals were classified as cured (C), dissociated, or not cured (NC). Members of group C (the group without cardiac alterations) presented significantly stronger proliferative response against the parasite antigens, with secretion of high levels of IFN-gamma in comparison with the NC group, raising a question about the role of this cytokine in the curing of human T. cruzi infection. Severe cardiac alterations were observed only in 1 of 25 patients, which suggests that treatment benefited the patients.

Acute Disease↗

Clinical course of hurricane keratopathy.

BACKGROUND/AIMS: "Hurricane keratopathy" is the name given to the whorl pattern, highlighted with fluorescein, seen in situations where corneal epithelial cell turnover is exaggerated. Although the condition is well described, follow up data on patients with this condition and its sequelae have only been reported in corneal graft patients. The aim was to study the clinical course of hurricane keratopathy in corneal graft patients and contact lens wearers, and to document any sequelae of this condition. METHODS: Hurricane keratopathy, occurring in 20 eyes with corneal grafts and 16 eyes (six bilateral) wearing rigid gas permeable contact lenses, was studied and followed. The occurrence, pattern, progress, resolution, and residual effects of the whorls were noted. RESULTS: Hurricane keratopathy was noted to occur in grafts as previously reported and also in contact lens wearers, which has hitherto not been reported. The whorls usually appeared within the first 3 weeks postoperatively and persisted up to 4 months. A small epithelial defect (11.1%), heaped epithelial cells (5.6%), and a nebular grade opacity (2.8%), were the only significant sequelae noted at the epicentre of the whorls. Resolution occurred from the periphery towards the centre of the cornea. CONCLUSIONS: The whorl pattern is sustained as long as the stimulus for increased cell turnover is maintained. Once this stimulus is eliminated, the pattern tends to resolve spontaneously.

Aged↗

The role of antiarrhythmic therapy in the management of nonsustained ventricular tachycardia.

The incidence of nonsustained ventricular tachycardia (NSVT) after myocardial infarction (MI), has decreased significantly in the thrombolytic era and may not have a high enough power to predict sudden cardiac death or all-cause mortality post-MI. Nonetheless, noninvasive algorithms that utilize the combination of NSVT with left ventricular dysfunction, abnormal signal-averaged electrocardiogram, and heart rate variability can be used for better risk assessment. Recent multicenter studies have provided strong evidence for the use of an implantable cardioverter defibrillator in patients with NSVT and inducible sustained ventricual tachycardia. On the other hand anti-arrhythmic drugs have no role and most are harmful in asymptomatic patients post-MI with NSVT.

Adrenergic beta-Antagonists↗

Corneal transplantation in young children with congenital hereditary endothelial dystrophy. Multicenter Pediatric Keratoplasty Study.

PURPOSE: To describe the surgical success rate and visual results of penetrating keratoplasty in a series of young children with congenital hereditary endothelial dystrophy and to summarize the current literature on outcomes of keratoplasty for congenital hereditary endothelial dystrophy, with particular attention to the timing of surgery. METHODS: The authors conducted a retrospective study of children aged 12 years and younger who underwent penetrating keratoplasty between 1975 and 1994 at four participating eye centers, and who were followed for at least 6 months postoperatively. For this report, 21 corneal transplants performed in 16 eyes of nine patients with congenital hereditary endothelial dystrophy were studied. Patients' median age at the time of first keratoplasty was 40 months (range, 3 months to 10 years). RESULTS: During a mean follow-up period of over 70 months (range, 6 to 240 months), 11 (69%) of 16 eyes retained full graft clarity. The 2-year survival rate of first grafts was 71% (95% confidence interval, 47% to 95%). Postoperative visual acuity improvement of 1 or more Snellen lines was seen in five of 10 eyes in which the patients were old enough for accurate assessment of visual acuity; however, just four of these 10 eyes attained a visual acuity of 20/200 or better. CONCLUSIONS: Penetrating keratoplasty for congenital hereditary endothelial dystrophy in children has a reasonable chance of surgical success when performed at a young age; however, the prognosis for improved visual acuity in children appears to be more guarded. Decisions on the timing of surgical intervention for congenital hereditary endothelial dystrophy should be made on a case-by-case basis. Although the threat of irreversible amblyopia in untreated eyes and good surgical success rates even among very young children argue for the consideration of relatively early surgical intervention in the most severely affected cases, there is evidence to support delaying surgery in some cases.

Child↗

Oral d,l sotalol reduces the incidence of postoperative atrial fibrillation in coronary artery bypass surgery patients: a randomized, double-blind, placebo-controlled study.

OBJECTIVES: The purpose of this prospective, randomized, double-blind, placebo-controlled study was to assess the efficacy of preoperatively and postoperatively administered oral d,l sotalol in preventing the occurrence of postoperative atrial fibrillation (AF). BACKGROUND: Atrial fibrillation is the most common arrhythmia following coronary artery bypass surgery (CABG). Its etiology, prevention and treatment remain highly controversial. Furthermore, its associated morbidity results in a prolongation of the length of hospital stay post-CABG. METHODS: A total of 85 patients, of which 73 were to undergo CABG and 12 CABG plus valvular surgery (ejection fraction > or = 28% and absence of clinical heart failure), were randomized to receive either sotalol (40 patients; mean dose = 190 +/- 43 mg/day) started 24 to 48 h before open heart surgery and continued for four days postoperatively, or placebo (45 patients, mean dose = 176 +/- 32 mg/day). RESULTS: Atrial fibrillation occurred in a total of 22/85 (26%) patients. The incidence of postoperative AF was significantly (p = 0.008) lower in patients on sotalol (12.5%) as compared with placebo (38%). Significant bradycardia/hypotension, necessitating drug withdrawal, occurred in 2 of 40 (5%) patients on sotalol and none in the placebo group (p = 0.2). None of the patients on sotalol developed Torsade de pointes or sustained ventricular arrhythmias. Postoperative mortality was not significantly different in sotalol versus placebo (0% vs. 2%, p = 1.0). Patients in the sotalol group had a nonsignificantly shorter length of hospital stay as compared with placebo (7 +/- 2 days vs. 8 +/- 4 days; p = 0.24). CONCLUSIONS: The administration of sotalol, in dosages ranging from 80 to 120 mg, was associated with a significant decrease (67%) in postoperative AF in patients undergoing CABG without appreciable side effects. Sotalol should be considered for the prevention of postoperative AF in patients undergoing CABG in the absence of heart failure and significant left ventricular dysfunction.

Administration, Oral↗

Intrathecal adenosine interacts with a spinal noradrenergic system to produce antinociception in nerve-injured rats.

BACKGROUND: Adenosine analogs produce antinociception in animal models of acute pain, reduce hypersensitivity in models of inflammatory and nerve-injury pain, and stimulate neurotransmitter release in the brain. Adenosine itself is entering clinical trials for analgesia, and the current study examined the effect, mechanisms of action, and interaction with noradrenergic systems of intrathecal adenosine in a rat model of neuropathic pain. METHODS: The left L5 and L6 spinal nerve roots were ligated and, 1 week later, an intrathecal catheter was inserted in male rats. Withdrawal threshold to mechanical stimulation of the left hind paw was determined before and after surgery, confirming mechanical hypersensitivity. The effects of intrathecal adenosine, clonidine, and their combination on withdrawal threshold were determined, and reversal of the effects of adenosine by adenosine and alpha2-adrenergic antagonists and by destruction of noradrenergic nerve terminals was tested. Finally, spinal cord slices were perfused in vitro with the adenosine agonist 5'-N-ethylcarboxamide adenosine, and norepinephrine release was measured. RESULTS: Intrathecal adenosine and clonidine reduced hypersensitivity and interacted in an additive manner. The effects of adenosine were blocked by intrathecal injection of A1 but not A2 adenosine receptor antagonists, by an alpha2-adrenergic antagonist, and by destruction of spinal noradrenergic nerve terminals. Perfusion of spinal cord slices with 5'-N-ethylcarboxamide adenosine resulted in a concentration-dependent increase in norepinephrine release. CONCLUSION: These data support clinical examination of intrathecal adenosine alone and with clonidine in the treatment of chronic pain states that include a component of mechanical hypersensitivity and suggest that, after nerve injury, adenosine acts to reduce hypersensitivity through spinal norepinephrine release.

Adenosine↗

Late complications in patients with pectoral defibrillator implants with transvenous defibrillator lead systems: high incidence of insulation breakdown.

As the majority of ICDs with transvenous leads are now implanted in the pectoral region, complications associated with the technique are being identified. To determine the incidence of lead complications in patients with transvenous defibrillator leads and ICDs implanted in the pectoral region, 132 unselected consecutive patients with transvenous defibrillator leads had ICDs implanted in the pectoral region. Three lead systems were used: (1) lead system 1 (45 patients) consisted of a transvenous pacing sensing lead and a superior vena cava coil with a submuscular patch used for defibrillation; (2) lead system 2 (36 patients) utilized a CPI Endotak lead system; and (3) lead system 3 (51 patients) utilized a Medtronic Transvene lead system. Patients were followed for 3-54 months (cumulative 2,269, mean 18 months). The average duration of follow-up with the three systems was 32, 12 and 11 months, respectively. At 30 months follow-up, all three lead systems had a low incidence of complications. However, there was a 13% overall incidence (45% actuarial incidence) of erosion of the insulation of the pacing sensing lead of system 1 at 50 months of follow-up. All lead complications were seen in patients with ICDs whose weights were > 195 g and volumes > 115 cc. The erosion was probably a consequence of the pressure by the large ICD against the lead in the pectoral pocket. Follow-up with lead systems 2 and 3 is relatively short (average 12 months) but no lead erosions were seen. Pectoral implantation of ICDs with long transvenous leads and large generators is associated with a moderate risk of late complications in the form of insulation breaks caused by pressure of the generator against the leads. The use of less redundant leads coupled with smaller ICDs will probably eliminate this complication.

Defibrillators, Implantable↗

Variable effects of adenosine on retrograde conduction in patients with atrioventricular nodal reentry tachycardia.

Adenosine has been demonstrated to reliably produce transient block of atrioventricular nodal (AVN) conduction, and has been advocated as a method of differentiating retrograde conduction via the atrioventricular node from accessory pathway conduction. However, the response of retrograde AVN to adenosine in patients with typical atrioventricular nodal reentry tachycardia (AVNRT) remains unclear. We evaluated 13 patients (mean age 45 +/- 20 years) with typical AVNRT prior to AVN modification. During right ventricular pacing, a rapid bolus of adenosine (0.2 mg/kg; maximum 18 mg) was administered. Adenosine sensitivity, defined by transient ventriculoatrial block, was observed in six patients, while in seven patients ventriculoatrial conduction was unaffected. An adenosine bolus administered during sinus rhythm or atrial pacing resulted in antegrade atrioventricular block in all the adenosine resistant patients in whom this was performed (n = 6). Comparisons of AVN electrophysiological characteristics between the adenosine sensitive and adenosine resistant patients were performed. There was no difference with respect to ventriculoatrial effective refractory period, ventriculoatrial Wenckebach, AVNRT cycle length, and His to atrial echo interval in AVNRT. However, there was a trend toward a longer antegrade fast pathway ERP in the adenosine sensitive group (P = 0.07). Electrophysiological properties do not predict retrograde AVN adenosine sensitivity. Adenosine does not cause retrograde AVN block in all patients with AVNRT, and therefore cannot reliably distinguish between retrograde conduction via the AVN or an accessory pathway.

Adenosine↗

Uncommon atrial flutter: characteristics, mechanisms, and results of ablative therapy.

Thirty-seven patients with atrial flutter were studied with catheter mapping and radiofrequency ablation. Uncommon atrial flutter occurred in 20 out of 37 (54%) patients. Atrial endocardial mapping showed two types of uncommon atrial flutter. In 15 patients (group I) it was characterized by a single clockwise circuit whereas in 5 patients (Group II) it was characterized by the presence of more than one circuit and/or localized atrial fibrillation. RFA ablation was acutely successful in 14 out of 15 patients (93%) in Group I and in 2 out of 5 (40%) patients in Group II. On long-term follow-up a significantly larger number of patients in Group I versus Group II (86% vs 20%) remained free of atrial flutter recurrence. We conclude that uncommon atrial flutter is a heterogeneous entity involving one or more reentrant circuits. Uncommon atrial flutter with multiple circuits may not be suitable for RFA.

Adult↗

IFN-gamma in human Chagas' disease: protection or pathology?

An apparently paradoxical role for IFN-gamma in human Chagas' disease was observed when studying the pattern of cytokine production by peripheral blood mononuclear cells (PBMC) obtained from two groups of chagasic patients after specific stimulation with Trypanosoma cruzi-derived antigens. The groups studied were 1) patients treated with benznidazole during the acute phase of Trypanosoma cruzi infection and 2) chronically infected untreated patients. In the treated group, higher levels of IFN-gamma were produced by PBMC from individuals cured after treatment when compared to non-cured patients. In contrast, in the chronically infected group (not treated) higher levels of IFN-gamma were produced by PBMC from cardiac patients in comparison with asymptomatic (indeterminate) patients. This apparently paradoxical role for IFN-gamma in human Chagas' disease is discussed in terms of the possibility of a temporal difference in IFN-gamma production during the initial stages of the infection (acute phase) in the presence or absence of chemotherapy. The maintenance of an immune response with high levels of IFN-gamma production during the chronic phase of the infection may favor cure or influence the development of the cardiac form of the disease.

Chagas Disease↗