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Biomedical subjects

M B Wagner

Publications and source records attributed to M B Wagner.

At least 19 recordsLinked to original sources

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.

Chronic Disease↗

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.

Adolescent↗

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.

Adolescent↗

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.

Adult↗

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.

Adult↗

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.

Action Potentials↗

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.

1-Methyl-3-isobutylxanthine↗

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).

Action Potentials↗

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.

Animals↗

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.

Animals↗

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.

Action Potentials↗

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.

Anti-Bacterial Agents↗

Estimating hidden prevalence in Hansen's disease through diagnosis delay and grade of disability at time of diagnosis.

The objective of the present study was to propose a new method for the calculation of estimated hidden prevalence (EHP) in Hansen's disease (HD). We analyzed the records of 4142 HD patients diagnosed in the state of Rio Grande do Sul, Brazil, between 1970 and 1991. Out of these 4142 cases, 3291 patients had their grade of disability (GD) evaluated at the time of diagnosis and provided information about the time elapsed between the appearance of the symptoms and the moment when HD was identified by a physician (diagnosis delay, DD). Mean DD for the sample (in years) was 1.51 for disability grade 0, 2.14 for grade 1, 4.46 for grade 2, and 9.64 for grade 2. EHP was calculated taking into account only two strata of GD using the formula HP = [(NC-GD 0/1) x 2.0 + (CN-GD 2/3) x 5.0]/(CGE x PCP), where: NC-GD 0/1 = mean annual number of newly detected grades 0 or 1 cases; CN-GD 2/3 = mean annual number of newly detected grades 2 or 3 cases; CGE = proportion of newly detected cases with GD evaluated; PCP = proportion of the population covered by the state HD control program; 2.0 and 5.0 correspond to an approximation of the mean time in years of DD in each respective stratum of GD. Applying this model, we found an EHP of 529 cases which translates to an excess of 0.58 cases/10,000 population. We also conducted a multivariate analysis using a logistic regression model. This analysis revealed that, in addition to DD, other variables such as clinical form, age group, sex and mode of detection were independent risk factors for the presence of disabilities. We also found two significant effect modification factors: DD versus clinical form and DD versus age group. Taking these findings into consideration, a more complex model was used to calculate the EHP with 16 strata (defined by clinical form of the disease, age group, and GD from 0 to 3). An EHP of 502 cases (excess of 0.55/10,000) was obtained with this more complex model. This result differs only 5% from that of the simplified model. Therefore, we conclude that the simplified model is indicated to estimate hidden prevalence of HD in the field.

Adult↗

Electrical interactions among real cardiac cells and cell models in a linear strand.

Previous work with model systems for action potential conduction have been restricted to conduction between two real cells or conduction between a model cell and a real cell. The inclusion of additional elements to make a linear strand has allowed us to investigate the interactions between cells at a higher level of complexity. When, in the simplest case of a linear strand of three elements, the conductance between elements 2 and 3 (GC2) is varied, this affects the success or failure of propagation between elements 1 and 2 (coupled by GC1) as well as the success or failure of propagation between elements 2 and 3. Several major features were illustrated. 1) When GC1 was only slightly greater than the coupling conductance required for successful propagation between a model cell and a real cell, addition of a third element of the strand either prevented conduction from element 1 to element 2 (when GC2 was high) or allowed conduction from element 1 to element 2 but not conduction from element 2 to element 3 (when GC2 was low). 2) For higher levels of GC1, there was an allowable "window" of values of GC2 for successful conduction from element 1 through to element 3. The size of this allowable window of GC2 values increased with increasing values of GC1, and this increase was produced by increases in the upper bound of GC2 values. 3) When the size of the central element of the strand was reduced, this facilitated conduction through the strand, increasing the range of the allowable window of GC2 values. The overall success or failure of conduction through a structure of cells that has a spatially inhomogeneous distribution of coupling conductances cannot be predicted simply by the average or the minimum value of coupling conductance but may depend on the actual spatial distribution of these conductances.

Animals↗

Risk factors for bleeding in major abdominal surgery using heparin thromboprophylaxis.

BACKGROUND: Patients undergoing major abdominal surgery are at risk of both bleeding and thrombotic complications and usually receive heparin thromboprophylaxis. PATIENTS AND METHODS: Risk factors for perioperative bleeding were examined in 3,809 patients in a double-blind, randomized trial investigating heparin thromboprophylaxis. The risk factors were modeled by logistic regression, and a risk score was calculated using the significant factors in the model. RESULTS: Bleeding was associated with the following factors in the model, given as adjusted odds ratios (ORa [95% confidence interval]): male sex (ORa 1.68 [1.21 to 2.34] P = 0.003), malignancy (ORa 1.69 [1.21 to 2.34] P = 0.008), gynecological surgery (ORa 1.62 [1.12 to 2.35] P = 0.011), and complex surgery (ORa 2.7 [2.02 to 3.62] P < 0.001). The risk of excessive bleeding for 0, 1, 2, and 3 risk factors was 2%, 6%, 11%, and 21%, respectively. CONCLUSIONS: The recognition of patients with these risk factors associated with perioperative bleeding should result in increased vigilance and may lead to modification of surgical and medical therapy.

Abdomen↗

Hospital-acquired infections among surgical patients in a Brazilian hospital.

A historical cohort study was conducted among surgical patients in a large general hospital in Porto Alegre, Brazil between March 1992 and May 1993. Data were collected by means of a retrospective chart review, which followed a standardized method based on the systematic review of all clinical and laboratory information available in the hospital records. The criteria for diagnosis of all hospital-acquired infections (HAIs) were based on those from the Centers for Disease Control, Atlanta. In total, 890 HAIs were detected among the 4199 patients included in the cohort. The incidence rate of HAIs for all sites combined was 21.20%. Incidence rates ranged from 2.95% for bloodstream infections to 8.65% for surgical wound infections. The overall incidence density was 16.32 HAIs per 1000 patient-days. Incidence densities ranged from 2.03 for bloodstream infections to 7.46 per 1000 patient-days for surgical wound infections. The median incubation period for surgical wound infections was seven days, and 29.4% of these infections were detected at post-discharge. Gram-negative bacteria were the most common organisms implicated in HAIs.

Adolescent↗

Modulation of propagation from an ectopic focus by electrical load and by extracellular potassium.

We previously developed a technique (R. Kumar, R. Wilders, R. W. Joyner, H. J. Jongsma, E. E. Verheijck, D. A. Golod, A. C. G. van Ginneken, and W. N. Goolsby. Circulation 94: 833-841, 1996) for study of a mathematical model cell with spontaneous activity, viz. a "real-time" simulation of a rabbit sinoatrial node cell (SAN model cell; R. Wilders, H. J. Jongsma, and A. C. van Ginneken. Biophys. J. 60: 1202-1216, 1991) simultaneously being electrically coupled via our "coupling clamp" [H. Sugiura and R. W. Joyner. Am. J. Physiol. 263 (Heart Circ. Physiol. 32): H1591-H1604, 1992] circuit to a real, isolated ventricular myocyte. We now apply this technique to investigate effects of coupling conductance (Gc), cell size, and the modulation of membrane potential by elevated extracellular potassium concentration on the ability of an ectopic focus, represented by the SAN model cell, to successfully drive a ventricular cell. Values of Gc and the relative sizes of the two cells define three possible outcomes: 1) spontaneous pacing of the SAN model cell but not driving of the ventricular cell, 2) cessation of spontaneous pacing, or 3) pacing of the SAN model cell and driving of the ventricular cell. Below a critical size of the SAN model cell only the first two of these outcomes is possible. Above this critical size there is a range of Gc that allows successful operation of the system as an ectopic focus. Elevation of extracellular potassium concentration from 4 to 8 mM increases both the lower bound and upper bound of Gc for this range. Elevation of extracellular potassium concentration, as commonly observed in myocardial ischemia, may have effects on either inhibiting or releasing from inhibition an ectopic focus.

Animals↗