Long-term follow-up of inactive occlusal caries lesions: 4-5-year results.

OBJECTIVE: To assess the clinical behavior of inactive caries lesion on the occlusal sites of permanent molars over 4-5 years and to estimate the risk for progression of caries-inactive sites compared with sound ones. METHODS: Clinical examinations were conducted at baseline (n = 258) and after 4-5 years and included the recording of dental plaque and dental caries at the occlusal surfaces and the eruption stage of each permanent molar. RESULTS: One hudred ninety-three schoolchildren were followed (response rate of 74.8%), totalizing 1152 teeth. Of the children, 30.6% (n = 59) presented at least one molar containing an active lesion, filling, or that had been extracted; according to the activity criterion, inactive lesions presented around a twofold increased risk for caries progression than sound surfaces (OR = 2.34 95%CI = 1.51-3.62). Thirteen percent (n = 25) of the children presented at least one molar progressing to dentine cavity, filling, or extraction; according to the severity criterion, inactive caries lesions presented a significantly higher risk for progression when compared with sound surfaces (OR = 2.69, 95% CI = 1.50-4.83). CONCLUSION: The vast majority of lesions (85-90%) identified as inactive enamel caries at baseline did not progress over 4-5 years. Despite this fact, it was possible to detect an increased risk for caries progression in caries-inactive occlusal sites compared with the sound ones. CLINICAL RELEVANCE: Considering the low progression rates, inactive caries lesions do not need a specific caries-controlling treatment and should be monitored longitudinally in the same manner as sound surfaces.

One-year evaluation of inactive occlusal enamel lesions in children and adolescents.

OBJECTIVES: The aims of this study were to compare caries incidence and progression on sound occlusal surfaces and on surfaces presenting inactive enamel lesions in children and adolescents over 1 year and to estimate the risk of caries incidence and progression on these surfaces. METHODS: This prospective cohort study followed 200 7-15-year-old caries-inactive schoolchildren over 1 year. Stage of eruption, occlusal plaque, and occlusal caries were recorded on permanent molars. Statistical analysis was performed using generalized estimating equations with a logistic link function. RESULTS: Twenty-two children (11 %) presented "caries progression" (at least one active lesion on molar teeth). At site level, no difference was observed in caries incidence and progression between sites classified either sound (2.6 %) or with inactive enamel lesion (3.9 %) at the baseline examination (χ (2) test, p = 0.48). Adjusted for plaque, stage of eruption, type of molar and dental arch, inactive enamel lesions presented a similar risk for caries progression than sound occlusal surfaces (OR = 0.98, 95 % CI = 0.40-2.38). CONCLUSION: Within the limitations of this study, no difference was observed in caries incidence, progression, and risk on sound occlusal sites in comparison with sites presenting inactive enamel lesions. CLINICAL RELEVANCE: Occlusal surfaces harboring inactive caries lesions did not require additional attention than the one normally given to sound occlusal surfaces over a 1-year period.

Eruption stage of permanent molars and occlusal caries activity/arrest.

This study assessed the association between the eruption stage of permanent second molars and occlusal caries activity among 12-year-old schoolchildren from South Brazil. A cross-sectional study was performed in Porto Alegre using a multistage probability sampling strategy to select a representative sample. Clinical examination was conducted to assess the eruption stage of permanent molars, Gingival Bleeding Index, and, after tooth cleaning and drying, caries experience (noncavitated and cavitated lesions, including caries activity assessment). Data were collected on sex, socioeconomic status, mother's education, brushing frequency, and consumption of soft drinks. Generalized estimating equations were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Overall, 983 schoolchildren with 3,071 second molars were available for analysis. Whereas active caries was observed in 6.6% of fully erupted permanent second molars, caries affected 26.2%, 29.6%, and 18.2% of erupting molars classified as stages 1, 2, and 3, respectively: stage 1, partially erupted occlusal surface; stage 2, fully erupted occlusal surface, <1/2 crown exposed; and stage 3, fully erupted occlusal surface, >1/2 crown exposed. After adjusting for socioeconomic and behavioral variables, partially erupted molars were significantly more likely to present active caries lesions than molars in full occlusion: stage 1, OR = 4.99 (95% CI = 3.38, 7.38); stage 2, OR = 5.18 (95% CI = 3.14, 8.53); stage 3, OR = 3.20 (95% CI = 2.21, 4.64). Similar results were found when clinical variables were included in the adjusted model. In conclusion, most occlusal caries lesions tend to arrest/revert when teeth reach the occlusal plan; however, an important proportion of these lesions remains active and in need of proper management. Children at risk should be targeted with preventive and minimally invasive strategies.

Influence of eruption stage and biofilm accumulation on occlusal caries in permanent molars: a generalized estimating equations logistic approach.

The aim of this study was to estimate the independent effects of biofilm accumulation and eruption stage on the occurrence of active caries lesions on occlusal surfaces of permanent molars. The sample consisted of 298 schoolchildren (6-15 years) who were examined by a calibrated examiner at a dental unit, using artificial light, a dental mirror and a WHO probe. The occurrence of visible biofilm on occlusal surfaces and the eruption stage of each permanent molar were recorded. After professional prophylaxis and air drying, the occlusal surfaces were classified as sound, caries-inactive or caries-active. To evaluate the association of eruption stage and biofilm accumulation with active caries lesions, a logistic regression model was used. Since data were clustered, odds ratios were obtained using generalized estimating equations with a logistic link function. 1,779 permanent molars were examined. All eruption stages were associated with active caries lesions. After adjustment for biofilm accumulation and type of molar, molars with occlusal surfaces partially exposed to the oral cavity were 63.6 times more susceptible to caries activity than molars with full occlusion (95% CI = 22.0-183.7). After adjustment for eruption stage and type of molar, teeth with a high degree of biofilm accumulation were 14.5 times more susceptible to caries activity than those without visible biofilm accumulation (95% CI = 6.5-32.4). No association between active caries and hardly detectable biofilm was found in this population. The present study found that the eruption stage of permanent molars is strongly associated with active caries lesions, adjusted for biofilm accumulation and type of molar.

European ancestry and cutaneous melanoma in Southern Brazil.

BACKGROUND: Similar to other countries, incidence and mortality rates for cutaneous melanoma (CM) are increasing in Brazil. Resulting from centuries of ethnic mixture, the skin of the Brazilian population presents all phototypes, being progressively lighter following the increase of the latitude toward the South, where the highest incidence of melanoma is observed. Studies from the United States and Argentina in whites suggest that European ancestry could represent an important risk factor for CM in those regions. METHODS: Questionnaires from a case-control study involving 119 melanoma patients and 177 controls were reviewed for age, gender, phototype, sun exposure, photoprotection and ancestry. The patients reported the countries of ancestry of their grandparents. Data were tabulated and converted into scores that would reflect the proportion of ancestry for each country in individuals. RESULTS: Patients with German and Italian ancestry presented higher risk for CM [odds ratio (OR), 3.5; 95% confidence interval (95% CI), 1.8-6.7 and OR, 9.7; 95% CI, 3.9-24.2, respectively]. Conversely, Brazilian indigenous ancestry showed a protective effect for the development of the disease, with an OR of 0.16 (95% CI, 0.04-0.7). CONCLUSIONS: Some European ancestries, especially German and Italian, seem to be associated to a higher risk of CM in this sample from Southern Brazil. On the other hand, Brazilian indigenous ancestry presented as a protection factor against developing the tumour.

Hypertension and Afro-descendant ethnicity: a bad interaction for lupus nephritis treated with cyclophosphamide?

Hypertension and ethnicity are important prognostic factors in evolution of lupus nephritis. A cohort of 75 patients with lupus nephritis treated with cyclophosphamide was conducted to investigate the evolution of creatinine levels between Caucasians and Afro-descendants. A multiple linear model was used to evaluate the combined effects of ethnicity and hypertension over delta creatinine controlling confounders. Sample characteristics were: 85% females; mean (+/-SD) age of 33.6 +/- 12.0 years; 77% Caucasians; 40% hypertensive at renal biopsy; 91% WHO class IV; mean basal creatinine: 1.5 +/- 1.3 mg/dL; mean final creatinine: 2.1 +/- 2.5 mg/dL; 40% anaemia; proteinuria: 5.4 +/- 4.8 g/day. Comparing Caucasians and Afro-descendants, it was found: 28.1% versus 72.2% for hypertension (P = 0.002); 31.6% versus 66.7% for anaemia (P = 0.018); 5.9 +/- 5.0 versus 3.8 +/- 4.0. g/day (P = 0.02) for proteinuria. Other comparisons including basal creatinine did not reach statistical significance. Comparing outcomes between Caucasians and Afro-descendants, it was found: 10.5% versus 22.2% for doubling of creatinine (P = 0.24); 0.41 +/- 2.03 versus 1.05 +/- 2.41 for delta creatinine ( P = 0.29); 8.8% versus 22.2% for haemodialysis (P = 0.21) and 3.5% versus 5.6% for death (P = 0.99). Analysing delta creatinine with multiple linear regression showed that hypertension had a significant overall effect (b = 0.80; SE = 0.32; P = 0.015), ethnicity alone was not significant (b = 0.35; SE = 0.29; P = 0.228); however, the effect of hypertension on delta creatinine was more intense among Afro-descendants than among Caucasians (interaction term b = - 0.83; SE = 0.37; P = 0.027). Afro-descendants lupus patients experience worst prognosis of renal function probably due to the effect of hypertension and not ethnicity per se.

Impact of a low-cost and simple intervention in enhancing treatment adherence in a Brazilian asthma sample.

The aim of this study was to evaluate adherence to treatment in persistent asthma in Brazil to determine the factors associated with non-adherence and to measure the efficacy of telephone calls in enhancing adherence. In a prospective, multicenter, interventional clinical trial with parallel groups, asthmatics were randomized into an intervention group or a control group. Asthmatics included in the intervention group received an initial telephone call to record demographic information and asthma characterization. After that, biweekly telephone calls were made to promote treatment adherence. Asthmatics included in the control group received only the initial and final telephone calls. Both groups received three packages of salmeterol/fluticasone for 3 months. The main outcome measure was the percentage of participants who took the prescribed doses of the drug. A total of 271 patients were included. The overall adherence rate was 51.9% for the control group and 74.3% for the intervention group. This meant a reduction of relative risk (RRR) of 47% (p < 0.001). The number needed to treat (NNT) was 4.5. The only variable associated with better adherence was severe persistent asthma. A low-cost easily implemented intervention, tailored to each individual, enhanced the adherence rate among Brazilian asthmatic patients.

No gender difference in effectiveness of smoking cessation treatment in a Brazilian real-life setting.

BACKGROUND: The clinical effectiveness of pharmacotherapy for smoking cessation in real-life settings has yet to be evaluated. OBJECTIVES: To assess the effectiveness of bupropion in general clinical practice for smoking cessation and to identify predictors of failure. METHODS: In an open, non-randomised study, smokers were recruited at the Smoking Cessation Clinics, Hospital Sao Lucas, Porto Alegre, Brazil. Subjects participated in a motivational group meeting, completed a standardised questionnaire and Fagerstrom test, and had their vital signs and exhaled CO registered. All participants received a prescription of bupropion and the same cognitive behaviour therapy. They attended eight weekly individual sessions, then monthly until the sixth month and a final session at month 12. The primary outcome measure was the rate of abstinence at 12 months. The predictor factors studied were sex, age, educational level, nicotine dependence, previous attempts and comorbidities. RESULTS: Among 253 smokers (62.5% females), abstinence rates at 6 months were 20.8% for males and 22.7% for females. The success rates dropped to 13.9% and 14.3% for males and females, respectively. CONCLUSIONS: Cognitive therapy plus bupropion for smoking cessation in real-life clinics in Brazil were similar to the efficacy found in clinical trials. No significant gender differences in success rates were found.

Quality of life and sexuality in chronic dialysis female patients.

Patients in end-stage renal disease (ESRD) present reduced quality of life (QOL) and impaired sexual function. Previous studies have mostly addressed male sexual dysfunction. This was a cross-sectional controlled study that applied a general and the World Health Organization Quality of Life-bref questionnaires to assess demographic, marital, and sexual conditions, and QOL in 86 healthy women aged 18 or more years (Group 1), and 38 female ESRD patients on dialysis for at least 2 months (Group 2). The effect of several explanatory variables upon QOL components was estimated. Quality of life was lower in Group 2 -- overall, and on physical and environment domains. To undergo dialysis and to be poorly educated negatively affected the QOL. Yet age, a stable marital relationship or being sexually active had no effect. Female patients undergoing chronic dialysis had lower QOL and were significantly more sexually dysfunctional than comparable healthy women. Decline in sexual function had no effect on the QOL.

Expression of cGMP-dependent protein kinase in human atrium.

We have shown that cGMP-dependent protein kinase (PKG) mediates stimulation of L-type calcium current by cGMP in rabbit atrial myocytes. The human atrium may have similar PKG-dependent regulation of calcium current. To elucidate the significance of PKG in cardiac function, we have isolated human PKG type I alpha cDNA (+1 to 2016), determined the nucleotide sequence and analyzed specific expression of PKG in human atrium. We obtained full-length cDNA of PKG type I alpha from human atrial RNA using reverse transcriptase-polymerase chain reaction (RT-PCR). The coding region of human cardiac PKG I alpha showed 99.9% homology to previously published human PKG I alpha except for base No. 1983. At this position G was substituted for T and this resulted in an amino acid substitution from Leu649 to Phe649. The cloned PKG I alpha cDNA was expressed in COS cells and the expressed PKG showed cGMP-stimulated PKG enzyme activity and immunoreactivity. Ribonuclease protection assay, Western blot analysis, and PKG enzyme activity assays in homogenates from human atrial tissue demonstrated the presence of PKG mRNA and protein in human atrial tissue. Immunofluorescence staining confirmed that PKG is highly expressed in human atrial myocytes. These findings suggest that PKG is highly expressed in human atrium and that PKG-dependent phosphorylation may be important in regulation of calcium channel activity in human atrial myocytes.

p53 protein in esophageal mucosa of individuals at high risk of squamous cell carcinoma of the esophagus.

Squamous cell carcinoma of the esophagus (SCCE) is diagnosed late and carries a poor prognosis. Biomarkers such as p53 protein expression may be present in the esophageal mucosa long before esophageal symptoms or lesions appear and may point toward early diagnosis. Asymptomatic subjects at high risk for SCEE (consumption of more than 80 g of ethanol and 10 cigarettes/day for at least 10 years) underwent upper gastrointestinal endoscopy with biopsies of the esophageal mucosa, and expression of p53 protein was compared with conventional histologic findings. In 182 subjects studied, p53 protein was expressed in a stepwise fashion according to the severity of the histologic findings: normal mucosa (12/103 or 11.7%), mild chronic esophagitis (6/43 or 14%), moderate chronic esophagitis (4/18 or 22.2%), severe chronic esophagitis (1/3 or 33.3%), low-grade dysplasia (4/11 or 36.4%), high-grade dysplasia (2/2 or 100%), and squamous cell carcinoma (2/2 or 100%) (P=0.00025). The odds ratio and confidence intervals were calculated by logistic regression, with multivariate adjustment for potentially confounding variables. The risk for p53 expression was twofold for moderate and severe chronic esophagitis and 10-fold for dysplasia and cancer (P=0.001). p53 protein was expressed not only in cancerous lesions, high-grade and low-grade dysplasia, as expected, but also in mucosa considered normal or with chronic esophagitis using conventional histology. Smokers and alcohol drinkers with normal mucosa or chronic esophagitis that express p53 protein may represent an unrecognized subgroup of individuals that may benefit from surveillance. Follow-up studies of these asymptomatic subjects and molecular analysis of the p53 gene are needed to clarify this point.

Fast pacing facilitates discontinuous action potential propagation between rabbit atrial cells.

We examined the critical coupling conductance (G(C)) for propagation at different pacing cycle lengths (CLs) (1,000 and 400 ms). As G(C) was progressively reduced, propagation failed at a CL of 1,000 ms, whereas propagation succeeded at a CL of 400 ms over a range of G(C) values before failing at a CL of 400 ms at a lower G(C), showing facilitation of propagation at the shorter CL. Critical G(C) was (means +/- SE) 0.8 +/- 0.1 nS for a CL of 400 ms and 1.3 +/- 0.1 nS for a CL of 1,000 ms (a 63% increase, P < 0.002, n = 9 cell pairs). In 14 uncoupled cells, action potential duration at 30% repolarization (APD(30)) increased from 19.9 +/- 2.5 to 41.8 +/- 2.6 ms (P < 0.001) as CL decreased from 1,000 to 400 ms. In five cell pairs, critical G(C) with 4-aminopyridine (4-AP) was reduced to 0.4 +/- 0.1 nS at a CL of 1,000 ms (P < 0.05 compared with control solution), and critical G(C) in 4-AP was unchanged by decreasing CL to 400 ms. It is possible that the "remodeling" of atrial cells due to atrial fibrillation or tachycardia, which has been shown to produce a decrease in the transient outward current, may result in an enhanced ability to propagate, possibly facilitating further development of fibrillation under conditions of decreased cellular coupling.

cGMP-dependent protein kinase mediates stimulation of L-type calcium current by cGMP in rabbit atrial cells.

OBJECTIVES: cGMP has been shown to exert both stimulatory and inhibitory effects on cardiac L-type calcium current (I(Ca)). The physiological role of cGMP in regulation of cardiac activity is still controversial. cGMP may be of importance in regulation of I(Ca) in atrial cells. The present study was focused on the role of cGMP in the modulation of I(Ca) in rabbit atrial cells. METHODS: Enzymatically isolated adult rabbit atrial cells were used to measure I(Ca) using whole cell voltage clamp. Expressed levels of cGMP-dependent protein kinase (PKG) were determined by Western blotting using PKG specific antibody in homogenates from atrial and ventricular cells. RESULTS: Nitrosoglutathione (GSNO), a nitric oxide donor that stimulates soluble guanylyl-cyclase to elevate cGMP levels increased I(Ca) while soluble G-cyclase inhibitors, ODQ or methylene blue inhibited I(Ca). Intracellular application of 8BrcGMP increased I(Ca) and blocked the inhibitory effect of methylene blue. KT-5823, an inhibitor of PKG inhibited I(Ca) and the stimulatory effect of GSNO was completely blocked ODQ or KT-5823. Inhibition of cAMP dependent protein kinase (PKA) by the 6-22 peptide completely blocked the stimulation of I(Ca) by the beta-agonist isoproterenol but not by GSNO. The potency of isoproterenol to stimulate I(Ca) was very high for atrial cells (EC(50) 2.4+/-0.6 nM) and only 100 nM isoproterenol was required to stimulate I(Ca) maximally (21.4+/-0.7 pA/pF) to a level (23.8+/-1.6 pA/pF) achieved with the inclusion of 100 microM cAMP in the pipette solution. GSNO produced an additive effect on I(Ca) already stimulated by either 10 microM isobutylmethylxanthine (phosphodiesterase inhibitor) or a low concentration (1 nM) isoproterenol but failed to produce any effect on I(Ca) maximally stimulated by 100 nM isoproterenol. Inhibition of PKG by KT-5823 significantly decreased the efficacy of isoproterenol and the maximal I(Ca) achieved with 100 nM isoproterenol was decreased to 8.2+/-0.6 pA/pF in the presence of KT-5823. Western blot analysis showed much higher expression of PKG in atrial cells compared to ventricular cells. CONCLUSIONS: These findings suggest that stimulatory effects of cGMP on I(Ca) in rabbit atrial cells are likely to be mediated via PKG dependent phosphorylation of calcium channels or associated proteins and that the effects of cGMP are not antagonistic to cAMP. PKG is highly expressed in atrial cells and PKG dependent phosphorylation may be necessary for maintaining basal I(Ca) and fully stimulating I(Ca) by beta-adrenergic activation in atrial cells.

A spontaneously active focus drives a model atrial sheet more easily than a model ventricular sheet.

Tachycardias can be produced when focal activity at ectopic locations in either the atria or the ventricles propagates into the surrounding quiescent myocardium. Isolated rabbit atrioventricular nodal cells were coupled by an electronic circuit to a real-time simulation of an array of cell models. We investigated the critical size of an automatic focus for the activation of two-dimensional arrays made up of either ventricular or atrial model cells. Over a range of coupling conductances for the arrays, the critical size of the focus cell group for successful propagation was smaller for activation of an atrial versus a ventricular array. Failure of activation of the arrays at smaller focus sizes was due to the inhibition of pacing of the nodal cells. At low levels of coupling conductance, the ventricular arrays required larger sizes of the focus due to failure of propagation even when the focus was spontaneously active. The major differences between activation of the atrial and ventricular arrays is due to the higher membrane resistance (lower inward rectifier current) of the atrial cells.

Assessing the antimicrobial prescription request process in a teaching hospital in Brazil: regulations and training.

It is known that antimicrobials are often prescribed inappropriately. One method used to deal with this problem is to regulate antimicrobial use by monitoring prescriptions. We report a study of physician compliance with the request for antibiotic process which was prepared and reviewed by a special infection control committee in our hospital the Nosocomial Infection Prevention Service (SCIH). The objective of this study was to identify the profile of inappropriate requests for restricted therapeutic antimicrobials used at Nossa Senhora da Conceição Hospital (HNSC), in Porto Alegre, Brazil. All 3,389 requests for therapeutic antimicrobials made between May 20, and October 31, 1996, were assessed and classified as appropriate and inappropriate. We determined that 17. 8% of the requests were inappropriate (a total of 720 errors). These were categorized according to 12 reasons for inappropriateness. Of these, the 3 most frequent inappropriate requests were deviation from standard use (26.73%), inappropriate length of treatment (23. 19%), and unfounded justification (13.61%). The reasons for inappropriateness were also arranged in three categories considering the following aspects: I. technical (59%); II. compatibility with the institutional program (32.36%), and III. administrative (8.61%). The 720 requests that were initially rejected were evaluated to see how antibiotic use was affected. In approximately 400 (55%), the forms could be appropriately modified after discussion with the physician. We conclude from this study that most of the inappropriate requests for antimicrobials in our hospital can be remedied by educating the staff since the errors were largely technical in nature. Thus, the SCIH should focus more on its role as an educational rather than as a regulatory body. By expanding this educational role, we anticipate improved physician compliance with our guidelines, and more appropriate antimicrobial prescribing and usage.

Measurements of calcium transients in ventricular cells during discontinuous action potential conduction.

The L-type calcium current (I(Ca)) is important in sustaining propagation during discontinuous conduction. In addition, I(Ca) is altered during discontinuous conduction, which may result in changes in the intracellular calcium transient. To study this, we have combined the ability to monitor intracellular calcium concentration ([Ca(2+)](i)) in an isolated cardiac cell using confocal scanning laser fluorescence microscopy with our "coupling clamp" technique, which allows action potential propagation from the real cell to a real-time simulation of a model cell. Coupling a real cell to a model cell with a value of coupling conductance (G(C) = 8 nS) just above the critical value for action potential propagation results in both an increased amplitude and an increased rate of rise of the calcium transient. Similar but smaller changes in the calcium transient are caused by increasing G(C) to 20 nS. The increase of [Ca(2+)](i) by discontinuous conduction is less than the increase of I(Ca), which may indicate that much of [Ca(2+)](i) is the result of calcium released from the sarcoplasmic reticulum rather than the integration of I(Ca).

Electrical interactions between a real ventricular cell and an anisotropic two-dimensional sheet of model cells.

We have extended our "coupling clamp" technique, in which we couple a real cell to a real-time simulation of a model cell, to now incorporate a real cardiac cell as the central element of a two-dimensional sheet of model cells, in which the coupling conductances may be different in the x and y directions and a specific region of lack of coupling conductance may serve as a resistive barrier. We stimulated the real cell in the central location and determined the critical size of the real cell for successful activation of the entire sheet. We found that this critical size was decreased when anisotropy was present compared with the isotropic case and was further decreased when the central site of stimulation was close to the resistive barrier. The heart normally has some degree of anisotropy, and it has been shown that the remodeling that occurs in peri-infarction zones produces a particular loss of lateral connections compared with end-to-end connections among heart cells. We propose that the normal existence of anisotropy and enhancement of the degree of anisotropy both by loss of lateral gap junctions and the development of resistive barriers may play a facilitating role in the development of ectopic foci that may lead to cardiac arrhythmias.

Effects of anisotropy on the development of cardiac arrhythmias associated with focal activity.

The anisotropy that normally exists in the myocardium may be either enhanced in peri-infarction zones by loss of lateral cell connections or reduced by redistribution of gap junctions. To test how the degree of anisotropy affects the development of ectopic focal activity, we carried out computer simulations in which a model of an ectopic focus is incorporated as the central element of a two-dimensional sheet of ventricular cells. At low values of intercellular coupling conductance (Gc), the focus region is spontaneously active, but the limited intercellular current flow inhibits propagation. At high Gc, automaticity is suppressed by the loading effects of the surrounding cells. At intermediate Gc, the ectopic activity may propagate into the sheet. In the case of isotropic coupling, the minimum size of the focus region for propagation to occur (in terms of number of collaborating cells within the focus) is as small as approximately ten cells, and this number decreases with increasing anisotropy. Thus, the presence of anisotropy facilitates the development of ectopic focal activity. We conclude that the remodeling that occurs in peri-infarction zones may create a substrate that either facilitates (enhanced anisotropy) or inhibits (reduced anisotropy) the development of cardiac arrhythmias associated with ectopic focal activity.