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Delineation of muscarinic receptor domains conferring selectivity of coupling to guanine nucleotide-binding proteins and second messengers.

The cloning and functional expression of five mammalian muscarinic acetylcholine receptor genes (m1-m5) has revealed that m1, m3, and m5 primarily couple to stimulation of phosphoinositide (PI) turnover, whereas m2 and m4 are strongly linked to inhibition of adenylate cyclase, albeit not exclusively. To identify the structural domains responsible for this functional specificity, cDNAs encoding chimeric m2/m3 receptors were constructed. The abilities of these receptors to mediate stimulation of PI hydrolysis and inhibition of prostaglandin E2-stimulated cAMP accumulation, as well as the pertussis toxin (PTX) sensitivity of these responses, were examined after stable expression in mouse A9 L cells. Substitution of the putative third cytoplasmic loop (i3) of m2 with the corresponding m3 sequence resulted in a chimeric receptor that, similar to m3, stimulated PI breakdown by a PTX-insensitive mechanism but did not inhibit adenylate cyclase. Conversely, a chimeric m3 receptor containing the i3 domain of m2 showed the same functional profile as m2 (i.e., inhibition of adenylate cyclase and weak stimulation of PI turnover by a PTX-sensitive mechanism), indicating that the i3 loop is sufficient to determine coupling selectivity. Similarly, exchange of a short N-terminal segment of i3 (16 or 17 amino acids) between m2 and m3 resulted in chimeric receptors that gained the ability to mediate the functional responses of the wild-type receptor from which the segment was derived, although with substantially reduced efficiency. However, the chimeric m2 receptor containing the 17-amino acid m3 sequence in the N-terminal portion of i3 retained its ability to inhibit adenylate cyclase. Carbachol binding studies involving the use of the GTP analog 5'-guanylyl imidodiphosphate and PTX-pretreated cells generally correlated well with the functional findings. Our data indicate that the N-terminal portion of i3 is a sufficient but not the exclusive determinant of coupling selectivity displayed by the various muscarinic receptors.

Adenylate Cyclase Toxin↗

Examining the relationship between executive functions and restricted, repetitive symptoms of Autistic Disorder.

The executive function theory was utilized to examine the relationship between cognitive process and the restricted, repetitive symptoms of Autistic Disorder (AD). Seventeen adults with AD were compared to 17 nonautistic controls on a new executive function battery (Delis-Kaplin Executive Function Scales). Restricted, repetitive symptoms were measured by a variety of instruments (i.e., the Autism Diagnostic Observation Schedule, Autism Diagnostic Interview-Revised, Gilliam Autism Rating Scale, and the Aberrant Behavior Checklist). The study replicated the executive function profile that has been reported in adults with AD. In addition to the replication findings, the study found several executive processes (i.e., cognitive flexibility, working memory, and response inhibition) were highly related to the restrictive, repetitive symptoms of AD; whereas, other executive process (i.e., planning and fluency) were not found to be significantly correlated with restricted, repetitive symptoms. Similarly, we found an executive function model consisting of relative strengths and deficits was the best predictor of restricted, repetitive symptoms of autism. The implications for the executive function theory and how the theory predicts core symptoms of autism are discussed.

Adolescent↗

Pathways between profiles of family functioning, child security in the interparental subsystem, and child psychological problems.

This study was designed to delineate pathways between systems profiles of family functioning, children's emotional insecurity in the interparental relationship, and their psychological adjustment in a sample of 221 children and their parents. Consistent with family systems theory, cluster analyses conducted with assessments of marital, coparental, and parent-child functioning indicated that families fit into one of four profiles: (a) cohesive families, characterized by warmth, affection, and flexible well-defined boundaries in family relationships; (b) disengaged families, reflected in high levels of adversity and low levels of support across family subsystems; (c) enmeshed families, evidenced by high levels of discord and weak maintenance of relationship boundaries in the family unit; and (d) adequate families, defined by elevated parental psychological control within a larger family context of low discord and high warmth. In comparison to children in cohesive families, children in enmeshed and disengaged families exhibited greater signs of insecurity in the interparental relationship concurrently and internalizing and externalizing symptoms both concurrently and 1 year later. Structural equation models revealed that a latent, multimethod measure of insecurity in the interparental relationship partially mediated associations between family enmeshment and disengagement and children's psychological symptoms 1 year later. Results are discussed in relation to how they inform and refine a family-wide model of the emotional security hypothesis.

Adaptation, Psychological↗

Extracellular acidification induces human neutrophil activation.

In the current work, we evaluated the effect of extracellular acidification on neutrophil physiology. Neutrophils suspended in bicarbonate-buffered RPMI 1640 medium adjusted to acidic pH values (pH 6.5-7.0) underwent: 1) a rapid transient increase in intracellular free calcium concentration levels; 2) an increase in the forward light scattering properties; and 3) the up-regulation of surface expression of CD18. By contrast, extracellular acidosis was unable to induce neither the production of H2O2 nor the release of myeloperoxidase. Acidic extracellular pH also modulated the functional profile of neutrophils in response to conventional agonists such as FMLP, precipiting immune complexes, and opsonized zymosan. It was found that not only calcium mobilization, shape change response, and up-regulation of CD18 expression but also production of H2O2 and release of myeloperoxidase were markedly enhanced in neutrophils stimulated in acidic pH medium. Moreover, extracellular acidosis significantly delayed neutrophil apoptosis and concomitantly extended neutrophil functional lifespan. Extracellular acidification induced an immediate and abrupt fall in the intracellular pH, which persisted over the 240-s analyzed. A similar abrupt drop in the intracellular pH was detected in cells suspended in bicarbonate-supplemented PBS but not in those suspended in bicarbonate-free PBS. A role for intracellular acidification in neutrophil activation is suggested by the fact that only neutrophils suspended in bicarbonate-buffered media (i.e., RPMI 1640 and bicarbonate-supplemented PBS) underwent significant shape changes in response to extracellular acidification. Together, our results support the notion that extracellular acidosis may intensify acute inflammatory responses by inducing neutrophil activation as well as by delaying spontaneous apoptosis and extending neutrophil functional lifespan.

Antigen-Antibody Complex↗

[Effect of aprotinin on selected parameters of coagulation and drainage blood loss after cardiac operations in patients without coagulation disorders].

THE AIM OF THE STUDY: An estimation of influence of different doses of aprotynin on bleeding, coagulation parameters and safety of its use after coronary artery bypass grafting (CABG) in pts without coagulation disorders. MATERIAL AND METHODS: 91 patients underwent CABG, 73 men, 18 women in age 37 to 76 +/- 56.5 years. Patients were randomly assigned to 3 groups; Group I; 38 pts. 6.5 mln KIU aprotynin. Group II; placebo--30 pts. Group III; 23 pts. 2 mln. KIU. There were 4 measurements 1.--before operation, 2. after discontinuing CPB, 3.--6 h after operation, 4.--24 h after operation. We measured Hb, Ht, PLT Glucose, D-dimers, APTT, TT Fibrynogen, INR, AT3, Ca2+, factor V, VIII, GOT GPT CK, CK-MB, CRP, ACT concentration of Hb in drainage 6 h after operation. There were estimated: renal function profile, drainage loss, perioperative MI, mortality, reoperation rate due to bleeding. RESULTS: The level of blood count and coagulation parameters did not differ between the groups in any test periods. D-dimer levels were significantly higher in the placebo group than in group I and III. The decrease of fibrin degradation was not related to the dose of aprotynin. Drainage was insignificantly higher in placebo group. Renal function was impaired in neither group. Reoperation rate perioperative infarction and mortality did not differ between the groups, however was highest in group I. CONCLUSION: Aprotynin reduces blood loss after operation in CPB and decrease fibrin degradation independently to the dose of the drug. The high-dose of aprotynin may increase the risk of early graft occlusion in patients without coagulation disorders.

Adult↗

Neuropsychologic functioning in autism: profile of a complex information processing disorder.

Neurobehavioral theories of autism have hypothesized core deficits in sensory input or perception, basic attentional abilities or generalized attention to extrapersonal space, anterograde memory, auditory information processing, higher order memory abilities, conceptual reasoning abilities, executive function, control mechanisms of attention, and higher order abilities across domains. A neuropsychologic battery designed to investigate these hypotheses was administered to 33 rigorously diagnosed autistic individuals with IQ scores greater than 80, and 33 individually matched normal controls. Stepwise discriminant function was used to define the profile of neuropsychologic functioning across domains. The neuropsychologic profile in these autistic individuals was defined by impairments in skilled motor, complex memory, complex language, and reasoning domains, and by intact or superior performance in the attention, simple memory, simple language, and visual-spatial domains. This profile is not consistent with mental retardation or with a general deficit syndrome, but rather with a selective impairment in complex information processing that does not involve visual-spatial processing. This profile is not consistent with a single primary deficit, but with a multiple primary deficit model in which the deficit pattern within and across domains is reflective of the complexity of the information processing demands. This neuropsychologic profile is furthermore consistent with the neurophysiologic characterization of autism as a late information processing disorder with sparing of early information processing.

Adolescent↗

Complement, opsonins, and the immune response to bacterial infection in burned patients.

Studies were performed to evaluate complement, opsonins, and the immune response to bacterial infection in burned patients. Concentrations and functional acitivities of components of the classical and alternative complement pathways were measured in the sera of four septic, two bacteremic, and four nonseptic burned patients. In addition, heat-labile and heat-stable opsonic activity and agglutinin titers directed against the infecting bacterial strains were measured in the sera of the four septic patients and in an additional group of 11 septic burned patients with abnormal complement profiles. Functional activity of the alternative complement pathway and the concentration of properdin were shown to be persistently decreased during eight weeks postburn in the septic, bacteremic, and nonseptic burned patients; reduced classical pathway activity was demonstrated during the initial postburn period only in the septic patients. Two of the 15 septic patients had decreased heat-labile serum opsonic activity for their infecting bacterial strains, which occurred only during the initial postburn period. Heat-stable opsonins and agglutinin titers in the patients' sera directed against the infecting bacterial strains were equivalent to those in normal human sera, except for the agglutinin titers to Streptococcus faecalis which were increased in the patients' sera in comparison to the normal sera. These results indicate that the multiple complement abnormalities which occur in septic burned patients do not predispose these patients to bacterial infection by decreasing serum opsonic activity. Moreover, heat-stable immune IgG antibodies are not produced during septicemia which facilitate opsonization of the infecting bacterial strains in the absence of an intact complement system.

Adolescent↗

Evaluation of the gastric microbiota based on body mass index using 16S rRNA gene sequencing.

INTRODUCTION: Obesity is a multifactorial condition influenced by various factors, including the gut microbiota. However, the relationship between the gastric microbiota and obesity remains poorly understood. This study aimed to investigate the composition of gastric microbiota, excluding Helicobacter pylori, in relation to body mass index (BMI) and metabolic indicators. METHODS: Thirty participants undergoing health checkups were classified into three groups-normal weight (BMI 18.5-22.9), overweight (BMI 23.0-24.9), and obese (BMI ≥25.0)-with ten individuals per group. Those with H. pylori infection, atrophic gastritis, or intestinal metaplasia were excluded. Gastric microbiota from four antral biopsies per subject were analyzed using 16S rRNA sequencing and functional profiling by metagenomic prediction. RESULTS AND DISCUSSION: Alpha diversity (Gini-Simpson index) was significantly lower in the combined overweight/obese group than that in the normal group (P=0.049). Beta diversity analysis revealed clear group separation (Bray-Curtis, P=0.005; unweighted UniFrac, P=0.004). Significant species differences between the groups were observed; specifically, the abundances of Muribaculum gordoncarteri, Turicibacter bilis, and Duncaniella dubosii, were significantly reduced in the overweight/obese group. Functional predictions showed differential enrichment of pathways related to fatty acid, amino acid, vitamin, and carbohydrate metabolism across BMI categories. These findings suggest that alterations in the gastric microbiota may be linked to obesity and metabolic dysregulation.

Humans↗

Sexual function and endocrine profile in fertile women with type 1 diabetes.

OBJECTIVE: Aims of this study were 1) to assess sexual function and endocrine profile among fertile type 1 diabetic women during the follicular and luteal phases of the menstrual cycle, 2) to compare these results with those obtained among healthy fertile women who served as control subjects, and 3) to explore the correlations between sexual function and endocrine milieu among patients and control subjects during the follicular and luteal phases of the menstrual cycle. RESEARCH DESIGN AND METHODS: Fifty fertile women with type 1 diabetes and 47 healthy control subjects completed a semistructured medical interview and filled in self-administered validated instruments to evaluate sexual function, depression, and sexual distress. Venous blood samples were drawn to measure glycated hemoglobin and an endocrine profile during either the follicular or the luteal phase of the menstrual cycle. RESULTS: Type 1 diabetic women had decreased sexual function and increased sexual distress compared with control subjects during the luteal, but not the follicular, phase of the menstrual cycle. During the follicular phase, patients had lower estrogenic basal tone, lower "weak" androgen (namely Delta4-androstenedione and dehydroepiandrosterone sulfate) production, and lower free-triiodothyronine and free-thyroxine levels compared with control subjects. During the luteal phase, total testosterone levels were higher in patients than control subjects, while 17beta-estradiol and progesterone levels were lower in patients than control subjects. CONCLUSIONS: Among type 1 diabetic women, sexual function and sexual distress vary according to the phase of the menstrual cycle. This finding may have implications on the clinical assessment of sexual function in type 1 diabetic women.

Adult↗

Protease profiling using a fluorescent domino peptide cocktail.

Five hexapeptides were prepared containing, in a domino-type arrangement, all 25 possible dipeptides between (1) aromatic, (2) hydrophobic, (3) positively charged, (4) negatively charged, and (5) small and polar amino acids. The peptides were fluorescence labeled at the N-terminus with a (7-coumaryl)oxyacetyl group, allowing the selective detection of N-terminal cleavage products. The five peptides were used as a cocktail reagent in an HPLC analysis. The cocktail produced specific cleavage patterns, or fingerprints, for a variety of proteases. This domino peptide cocktail can be used as a general reagent for protease identification and functional profiling.

Chromatography, High Pressure Liquid↗

Selective assessment of single-lung graft function with 133Xe radiospirometry in acute rejection and infection.

In single-lung transplant recipients, the usefulness of spirometric indexes in detecting acute events involving the lung graft is limited due to the bias caused by the native lung. Selective functional monitoring is needed for the proper evaluation of complications after transplantation, but thus far, to our knowledge, no clinically feasible methods for selective graft-function assessment have been presented. In ten single-lung recipients, of whom six had a parenchymal lung disease and four had pulmonary hypertension, the relative ventilation (Vtx), perfusion (Qtx), and ventilation/perfusion ratio of the transplanted lung (V/Qtx) were determined with multidetector 133Xe radiospirometry. Additionally, the fractions of FEV1, FVC, and diffusing capacity for carbon monoxide (Dco) of the transplant (FEV1tx, FVCtx, Dcotx, respectively) were determined by using corresponding radiospirometric parameters for the calculation of their distribution between the lungs. The analysis included seven episodes of acute rejection and nine episodes of infection. The Qtx decreased during acute rejection but did not change during infection (p=0.001). Compared with the figures during infection, the V/Qtx increased during acute rejection significantly (p<0.05) in patients with underlying fibrosis or emphysema, but not in those with pulmonary hypertension. In detection of acute events, the sensitivity of the selective parameters, ie, FEV1tx (86%) and FVCtx (73%), was higher than that of the sum-function parameters, FEV1 (66%) and FVC (40%). Moreover, the sensitivity of Dcotx (80%) was higher than that of Dco (60%) in detecting acute rejection. The findings indicate that, in single-lung recipients with a parenchymal lung disease, the assessment of Qtx, V/Qtx, and Dcotx with a radioactive tracer can help to distinguish acute rejection from infection. The graft-selective parameters, ie, FEV1tx, FVCtx, and Dcotx, tended to be more sensitive than the corresponding sum-function parameters in detecting acute events, thus providing a more accurate functional profile of the single-lung graft.

Acute Disease↗

Neuronal nicotinic receptors in the human brain.

Neuronal nicotinic acetylcholine receptors (nAChRs) are a family of ligand gated ion channels which are widely distributed in the human brain. Multiple subtypes of these receptors exist, each with individual pharmacological and functional profiles. They mediate the effects of nicotine, a widely used drug of abuse, are involved in a number of physiological and behavioural processes and are additionally implicated in a number of pathological conditions such as Alzheimer's disease, Parkinson's disease and schizophrenia. The nAChRs have a pentameric structure composed of five membrane spanning subunits, of which nine different types have thus far been identified and cloned. The multiple subunits identified provide the basis for the heterogeneity of structure and function observed in the nAChR subtypes and are responsible for the individual characteristics of each. A substantial amount of information on human nAChR structure and function has come from studies on neuroblastoma cell lines which naturally express nAChRs and from recombinant nAChRs expressed in Xenopus oocytes. In vitro brain nAChR distribution can be mapped with a number of appropriate agonist and antagonist radioligands and subunit distribution may be mapped by in situ hybridization using subunit specific mRNA probes. Receptor distribution in the living human brain can be studied with noninvasive imaging techniques such as PET and SPECT, with a significant reduction in nAChRs in the brains of Alzheimer's patients having been identified with [11C] nicotine in PET studies. Despite the significant body of knowledge now accumulated about nAChRs, much remains to be elucidated. This review will attempt to describe the current knowledge on the nAChR subtypes in the human brain, their functional roles and neuropathological involvement.

Animals↗

Catecholamine-synthesizing enzymes and chromogranin proteins in drug-induced proliferative lesions of the rat adrenal medulla.

Both epinephrine (E) and norepinephrine (NE) cells in the rat adrenal medulla are able to proliferate in response to pharmacologic stimulation. However, previous biochemical studies have suggested that drug-induced or spontaneous pheochromocytomas in rats are almost invariably NE-producing. To resolve these apparently conflicting data, immunocytochemical techniques were utilized to establish functional profiles of adrenal medullary lesions classified as pheochromocytoma or nodular hyperplasia in rats treated chronically with a phosphodiesterase inhibitor which induced pheochromocytomas. Sixteen of 17 pheochromocytomas and all hyperplastic nodules stained positively for tyrosine hydroxylase and dopamine beta-hydroxylase, consistent with an ability to produce NE. No lesion of either type stained for phenylethanolamine N-methyltransferase, consistent with an inability to produce epinephrine. Lesions of both types showed variable staining for chromogranin proteins. The findings indicate that qualitative functional differences cannot be used to discriminate hyperplastic nodules from small pheochromocytomas in rats. Some lesions currently classified as hyperplastic nodules might in fact be small pheochromocytomas. Others might represent diffuse hyperplasia within pre-existing islands of NE-cells in a background of hyperplastic epinephrine-cells.

Adrenal Gland Neoplasms↗

Targeted screening for genetic haemochromatosis: a combined phenotype/genotype approach.

OBJECTIVE: To evaluate the clinical utility of a targeted screening approach for the detection of genetic haemochromatosis. METHODS: Screening by measuring fasting serum transferrin saturation (TS) and gene testing was carried out in patients in whom a raised serum alanine amino transferase (ALT) activity and raised random serum TS had been found on routine blood testing. RESULTS: During the 29 month study period, 32 patients homozygous for the C282Y genotype were detected from a catchment population of 330,000 by screening blood samples referred initially for routine laboratory liver function tests. By comparison, during the same period of time and within the same population, only seven patients were found by clinical suspicion alone. The patients in the study, after treatment by venesection, have shown both clinical and biochemical improvement. CONCLUSIONS: The study shows that from a population of patients in whom a routine liver function profile had been requested, it is possible to detect subjects homozygous for the C282Y HFE genotype who have clinical or biochemical markers of iron overload.

D-Alanine Transaminase↗

Arthritis and heart disease as risk factors for major depression: the role of functional limitation.

BACKGROUND: Major depression in later life is highest among people with chronic illness. Identifying amenable factors that mediate the relationship between known risk factors such as arthritis and heart disease with major depression is important to the design of clinical and public health strategies to reduce depression and its consequences. OBJECTIVE: This study investigates factors amenable to clinical and public health intervention that could mediate the relationship between chronic illness and major depression. DESIGN: Population-based national sample. SETTING: United States preretirement age (54-65) adults. PARTICIPANTS: A total of 7825 participants from the 1996 Health and Retirement Survey. MEASUREMENT: The outcome is major depression based on standardized assessment. Independent variables include sociodemographics chronic illness profile, functional limitation, health and medical access. RESULTS: A substantial burden of major depression is related to chronic illness, particularly arthritis (attributable risk [AR], 18.1%; 95% confidence interval [CI], 9.9-25.6) and heart disease (AR, 17.6%; 95% CI, 13.4-21.7). Functional limitation is the strongest investigated factor associated with depression (AR, 34.4%; 95% CI, 24.8-42.7) and attenuates the associations of arthritis and heart disease with depression. CONCLUSION: Functional limitation mediates the association of arthritis and heart disease with major depression. This relationship offers potential clinical and public health strategies to reduce major depression in older adults through intervention and management of functional limitation. Alternatively, it might be possible to reduce functional loss through screening for depression, particularly among people with functional limitation, and effective mental health treatment. The importance for clinical management of depression, comorbidity, and functional limitation spectrum supports the value of systems-based medicine.

Activities of Daily Living↗

A replication-competent chimera of plant and animal viruses.

Human, animal, fungal, and plant viruses encode papain-like proteinases that function in polyprotein processing, RNA synthesis, and virus-host interactions. To compare the functional profiles of diverse papain-like proteinases, we replaced a proteinase gene of the beet yellows virus (BYV) with those derived from equine arteritis virus (EAV), foot-and-mouth disease virus (FMDV), and the fungal virus CHV1. We found that, although each of the foreign proteinases efficiently processed the viral polyprotein, only the EAV proteinase supported vigorous replication of the chimeric BYV in plant protoplasts. This result demonstrated that the proteinases of BYV and EAV, but not FMDV or CHV1, provide a function that is critical for genome replication and that is separable from polyprotein processing. Further characterization of the BYV-EAV chimera revealed that BYV proteinase is also required for virus invasion and cell-to-cell movement. Thus, the same viral protein can combine both replication-related functions shared by plant and animal viruses and specialized functions in virus-host interactions.

Animals↗

A naturally processed mitochondrial self-peptide in complex with thymic MHC molecules functions as a selecting ligand for a viral-specific T cell receptor.

Peptide fragments of self-proteins bound to major histocompatibility complex molecules within the thymus are important for positively selecting T cell receptor (TCR)-bearing CD4(+)CD8(+) double positive (DP) thymocytes for further maturation. The relationship between naturally processed thymic self-peptides and TCR-specific cognate peptides is unknown. Here we employ HPLC purification of peptides released from H-2K(b) molecules of the C57BL/6 thymus in conjunction with mass spectrometry (MS) and functional profiling to identify a naturally processed K(b)-bound peptide positively selecting the N15 TCR specific for the vesicular stomatitis virus octapeptide (VSV8) bound to K(b). The selecting peptide was identified in 1 of 80 HPLC fractions and shown by tandem MS (MS/MS) sequencing to correspond to residues 68-75 of the MLRQ subunit of the widely expressed mitochondrial NADH ubiquinone oxidoreductase (NUbO(68-75)). Of note, the peptide differs at six of its eight residues from the cognate peptide VSV8 and functions as a weak agonist for mature CD8 single positive (SP) N15 T cells, with activity 10,000-fold less than VSV8. In N15 transgenic (tg) recombinase activating gene 2(-/)- transporter associated with antigen processing 1(-/)- fetal thymic organ culture, NUbO(68-75) induces phenotypic and functional differentiation of N15 TCR bearing CD8 SP thymocytes. Failure of NUbO(68-75) to support differentiation of a second K(b)-restricted TCR indicates that its inductive effects are not general.

Animals↗

Urodynamic changes induced by the intravaginal electrode during pelvic floor electrical stimulation.

AIMS: The goal of this study was to evaluate whether the intravaginal electrode used to perform vaginal electrical stimulation could induce acute changes on the cystometrograms and urethral pressure profiles (UPP) recordings. METHODS: Three consecutive urodynamic examinations were performed on 30 women with stress urinary incontinence (SUI) symptoms. The first exam was performed without the electrode, the second with the electrode inserted into the vagina, but with the stimulator switched off and the third with the stimulator turned on. We used the INNOVA (Empi) stimulator with electrical parameters set at 50 Hz and 60 mA and on an intermittent cycle during the cystometries and a continuous stimulation during the UPP. The data of functional profile length (FPL), maximum urethral closure pressure (MUCP), and area of the resting UPP, as well as the filling sensations and its respective bladder volumes during the cystometries, were compared. With regard to the cystometries. RESULTS: No effect of the electrode was observed on cystometry. However, the simple presence of the electrode improved the FPL, MUCP, and areas of the UPP similar to those when the stimulation was applied. CONCLUSIONS: We conclude that, the presence of the intravaginal electrode induces changes in the UPP not related to the stimulation itself. The physiotherapeutic effect of the electrode itself is still to be evaluated.

Adult↗