Pharyngeal clearance and pharyngeal transit time determined by a biomagnetic method in normal humans

Clearance and transit time are parameters of great value in studies of digestive transit. Such parameters are nowadays obtained by means of scintigraphy and videofluoroscopy, with each technique having advantages and disadvantages. In this study we present a new, noninvasive method to study swallowing pharyngeal clearance (PC) and pharyngeal transit time (PTT). This new method is based on variations of magnetic flux produced by a magnetic bolus passing through the pharynx and detected by an AC biosusceptometer (ACB). These measurements may be performed in a simple way. cause no discomfort. and do not use radiation. We measured PC in 8 volunteers (7 males and I female. 23-33 years old) and PTT in 8 other volunteers (7 males and I female. 21-29 years old). PC was 0.82 +/- 0.10 s (mean +/- SD) and PTT was 0.75 +/- 0.03 s. The results were similar for PC but longer for PTT than those determined by means of other techniques. We conclude that the biomagnetic method can be used to evaluate PC and PTT.

Oral and pharyngeal transit of a paste bolus in Chagas` disease

We measured the oral and pharyngeal transit of a paste bolus in 20 patients with Chagas` disease and 21 controls. Each subject swallowed of a 10-ml paste bolus prepared with 50 ml of water and 4.5 g of instant food thickener labeled with 55.5 MBq of 99(m) technetium phytate. After the scintigraphic recording of the transit, we delineated regions of interest (ROI) corresponding to mouth, pharynx, and proximal esophagus. Time-activity curves were generated for each ROI. There was no difference between patients with Chagas` disease and controls with respect to the duration of oral and pharyngeal transit, amount of pharyngeal residue, or flux of bolus entry into the proximal esophagus. The amount of oral residue was higher in patients with Chagas` disease (median = 0.71 ml) than in controls (median = 0.45 ml). The pharyngeal clearance duration was longer in patients with Chagas` disease (median = 0.85 s) than in controls (median = 0.60 s). The oral transit duration of the patients with Chagas` disease and dysphagia (median = 0.55 s, n = 14) was shorter than the oral transit duration of chagasic patients without dysphagia (median = 0.80 s, n = 6). We conclude that when swallowing a paste bolus, patients with Chagas` disease may have an increased amount of oral residue and a longer pharyngeal clearance duration than asymptomatic volunteers.

Evaluation of swallowing in children with vomiting after feeding

Vomiting after feeding is a symptom of gastroesophageal reflux (GER) and of eosinophilic esophagitis (EE), which are considered to be a cause of infant feeding disorder. The objective of the present study was to evaluate swallowing in children with feeding disorder manifested by vomiting after feeding. Using clinical and videofluoroscopic methods we studied the swallowing of 37 children with vomiting after feeding (mean age = 15.4 months), and of 15 healthy children (mean age = 20.5 months). In the videofluoroscopic examination the children swallowed a free volume of milk and 5 ml of mashed banana, both mixed with barium sulfate. We evaluated five swallows of liquid and five swallows of paste. The videofluoroscopic examination was recorded at 60 frames/s. Patients had difficulty during feeding, pneumonia, respiratory distress, otitis, and irritability more frequently than controls. During feeding, children with vomiting, choke were irritable, and refused food more frequently than controls, and during the videofluoroscopic examination the patients had more backward movement of the head than controls for both the liquid and paste boluses. There was no difference in the timing of oral swallowing transit, pharyngeal swallowing transit, or pharyngeal clearance between patients and controls. We conclude that children with vomiting after feeding may have difficulties in accepting feeding, although they have no alteration of oral and pharyngeal phases of swallowing.

Effect of Gender on Swallow Event Duration Assessed by Videofluoroscopy

There are data suggesting that women swallow liquids at a lower flow rate and ingest smaller volumes in each swallow than men. Our objective in this work was to compare swallowing in asymptomatic men and women by videofluoroscopy. We studied 18 men [age = 33-77 years, mean = 61 (10) years] and 12 women [age = 29-72 years, mean = 53 (15) years] who swallowed in duplicate 5 and 10 ml of liquid and paste barium boluses. None of the volunteers had dysphagia, neurologic diseases, or oral, pharyngeal, or esophageal diseases. The videofluoroscopic examination showed that for the 5-ml bolus, women had a longer oropharyngeal transit [liquid: men, 0.63 (0.21) s, women, 0.88 (0.39) s; paste: men, 0.64 (0.35) s, women, 0.94 (0.58) s], longer oral transit [liquid: men, 0.41 (0.21) s, women, 0.59 (0.35) s; paste: men, 0.39 (0.28) s, women, 0.59 (0.42) s], and longer pharyngeal clearance [liquid: men, 0.36 (0.11) s, women, 0.45 (0.16) s; paste: men, 0.42 (0.25) s, women, 0.56 (0.27) s] compared with men (p < 0.05). We conclude that there are differences in swallowing between men and women, with women having a longer oropharyngeal transit than men for a 5-ml bolus.

Reduced Insulin Clearance And Lower Insulin-degrading Enzyme Expression In The Liver Might Contribute To The Thrifty Phenotype Of Protein-restricted Mice.

Nutrient restriction during the early stages of life usually leads to alterations in glucose homeostasis, mainly insulin secretion and sensitivity, increasing the risk of metabolic disorders in adulthood. Despite growing evidence regarding the importance of insulin clearance during glucose homeostasis in health and disease, no information exists about this process in malnourished animals. Thus, in the present study, we aimed to determine the effect of a nutrient-restricted diet on insulin clearance using a model in which 30-d-old C57BL/6 mice were exposed to a protein-restricted diet for 14 weeks. After this period, we evaluated many metabolic variables and extracted pancreatic islet, liver, gastrocnemius muscle (GCK) and white adipose tissue samples from the control (normal-protein diet) and restricted (low-protein diet, LP) mice. Insulin concentrations were determined using RIA and protein expression and phosphorylation by Western blot analysis. The LP mice exhibited lower body weight, glycaemia, and insulinaemia, increased glucose tolerance and altered insulin dynamics after the glucose challenge. The improved glucose tolerance could partially be explained by an increase in insulin sensitivity through the phosphorylation of the insulin receptor/protein kinase B and AMP-activated protein kinase/acetyl-CoA carboxylase in the liver, whereas the changes in insulin dynamics could be attributed to reduced insulin secretion coupled with reduced insulin clearance and lower insulin-degrading enzyme (IDE) expression in the liver and GCK. In summary, protein-restricted mice not only produce and secrete less insulin, but also remove and degrade less insulin. This phenomenon has the double benefit of sparing insulin while prolonging and potentiating its effects, probably due to the lower expression of IDE in the liver, possibly with long-term consequences.

Evaluation Of The Location Of Capsules Swallowed With Food During The Pharyngeal Phase Triggering In Asymptomatic Adults.

To assess the location of hard gelatin capsules in the pharyngeal phase triggering among asymptomatic adults. The location of the bolus during the pharyngeal phase triggering provides information about the sensorimotor model of the beginning of deglutition onset. To evaluate the location of hard gelatin capsules in the pharyngeal phase triggering among asymptomatic adults. A videofluoroscopy swallowing study was carried out in 60 subjects (14 male and 46 female participants) aged between 27 and 55 years, who were evaluated with hard gelatin capsules #00 and #3 containing barium sulfate, swallowed with liquid food and pudding, in free volume. The first laryngeal elevation movement was the criterion to locate the pharyngeal phase triggering. Statistical analysis was based on the McNemar test. Capsule #3 presented higher percentage of location in the tongue dorsum compared to capsule #00, and capsule #00 presented higher percentage of location in the tongue base and vallecula compared to capsule #3. There was a difference between different capsules swallowed with liquid (p=0.016) and pudding (p=0.037). The capsule size influenced the location of the pharyngeal phase triggering. Smaller capsules started pharyngeal phase in the most anterior region (tongue dorsum) compared to larger capsules.

Inequalities in mortality of men by oral and pharyngeal cancer in Barcelona, Spain and Sao Paulo, Brazil, 1995-2003

Background: Large inequalities of mortality by most cancers in general, by mouth and pharynx cancer in particular, have been associated to behaviour and geopolitical factors. The assessment of socioeconomic covariates of cancer mortality may be relevant to a full comprehension of distal determinants of the disease, and to appraise opportune interventions. The objective of this study was to compare socioeconomic inequalities in male mortality by oral and pharyngeal cancer in two major cities of Europe and South America. Methods: The official system of information on mortality provided data on deaths in each city; general censuses informed population data. Age-adjusted death rates by oral and pharyngeal cancer for men were independently assessed for neighbourhoods of Barcelona, Spain, and Sao Paulo, Brazil, from 1995 to 2003. Uniform methodological criteria instructed the comparative assessment of magnitude, trends and spatial distribution of mortality. General linear models assessed ecologic correlations between death rates and socioeconomic indices (unemployment, schooling levels and the human development index) at the inner-city area level. Results obtained for each city were subsequently compared. Results: Mortality of men by oral and pharyngeal cancer ranked higher in Barcelona (9.45 yearly deaths per 100,000 male inhabitants) than in Spain and Europe as a whole; rates were on decrease. Sao Paulo presented a poorer profile, with higher magnitude (11.86) and stationary trend. The appraisal of ecologic correlations indicated an unequal and inequitably distributed burden of disease in both cities, with poorer areas tending to present higher mortality. Barcelona had a larger gradient of mortality than Sao Paulo, indicating a higher inequality of cancer deaths across its neighbourhoods. Conclusion: The quantitative monitoring of inequalities in health may contribute to the formulation of redistributive policies aimed at the concurrent promotion of wellbeing and social justice. The assessment of groups experiencing a higher burden of disease can instruct health services to provide additional resources for expanding preventive actions and facilities aimed at early diagnosis, standardized treatments and rehabilitation.

The Liver Plays a Major Role in Clearance and Destruction of Blood Trypomastigotes in Trypanosoma cruzi Chronically Infected Mice

Intravenous challenge with Trypanosoma cruzi can be used to investigate the process and consequences of blood parasite clearance in experimental Chagas disease. One hour after intravenous challenge of chronically infected mice with 5610 6 trypomastigotes, the liver constituted a major site of parasite accumulation, as revealed by PCR. Intact parasites and/or parasite remnants were visualized at this time point scattered in the liver parenchyma. Moreover, at this time, many of liver-cleared parasites were viable, as estimated by the frequency of positive cultures, which considerably diminished after 48 h. Following clearance, the number of infiltrating cells in the hepatic tissue notably increased: initially (at 24 h) as diffuse infiltrates affecting the whole parenchyma, and at 48 h, in the form of large focal infiltrates in both the parenchyma and perivascular spaces. Phenotypic characterization of liver-infiltrating cells 24 h after challenge revealed an increase in Mac1(+), CD8(+) and CD4(+) cells, followed by natural killer (NK) cells. As evidence that liver-infiltrating CD4(+) and CD8(+) cells were activated, increased frequencies of CD69(+) CD8(+), CD69(+) CD4(+) and CD25(+) CD122(+) CD4(+) cells were observed at 24 and 48 h after challenge, and of CD25(-)CD122(+)CD4(+) cells at 48 h. The major role of CD4(+) cells in liver protection was suggested by data showing a very high frequency of interferon (IFN)-gamma-producing CD4(+) cells 24 h after challenge. In contrast, liver CD8(+) cells produced little IFN-gamma, even though they showed an enhanced potential for secreting this cytokine, as revealed by in vitro T cell receptor (TCR) stimulation. Confirming the effectiveness of the liver immune response in blood parasite control during the chronic phase of infection, no live parasites were detected in this organ 7 days after challenge.

Clinical indicators of ineffective airway clearance in children with congenital heart disease

To analyse the sensitivity and specificity of clinical indicators of ineffective airway clearance in children with congenital heart disease and to identify the indicators that have high predictive power. The precise establishment of nursing diagnoses has been found to be one of the factors contributing to higher quality of care and cost reduction in healthcare institutions. The use of indicators to diagnose ineffective airway clearance could improve care of children with congenital heart disease. Longitudinal study. Participants consisted of 45 children, <= 1 year of age, with congenital heart disease, who had not had definitive or palliative surgical correction. Six assessments were made at 2-day intervals. Each clinical indicator was defined based on previously established operational criteria. Sensitivity, specificity and positive and negative predictive values of each indicator were calculated based on a model for the longitudinal data. A nursing diagnosis of ineffective airway clearance was made in 31% of patients on the first assessment, rising to 71% on the last assessment, for a 40% increase. Sensitivity was highest for Changes in Respiratory Rates/Rhythms (0.99), followed by Adventitious Breath Sounds (0.97), Sputum Production (0.85) and Restlessness (0.53). Specificity was higher for Sputum Production (0.92), followed by Restlessness (0.73), Adventitious Breath Sounds (0.70) and Changes in Respiratory Rates/Rhythms (0.17). The best positive predictive values occurred for Sputum Production (0.93) and Adventitious Breath Sounds (0.80). Adventitious Breath Sounds followed by Sputum Production were the indicators that had the best overall sensitivity and specificity as well as the highest positive predictive values. The use of simple indicators in nursing diagnoses can improve identification of ineffective airway clearance in children with congenital heart disease, thus leading to early treatment of the problem and better care for these children.

A second Candida albicans resistance gene (Carg2) regulates tissue damage, but not fungal clearance, in sub-lethal murine systemic infection

The severity of systemic infection with the yeast Candida albicans has been shown to be under complex genetic control. C57/L mice carry an allele that is associated with an increase in tissue destruction when compared with C57BI/6 mice; however, the gene affects only the severity of tissue lesions, and does not influence the magnitude of the fungal burden in either kidney or brain. Studies in [C57/L x C57BI/6]F1 hybrid mice, and [C57/L x C57BI/6]F1 x C57/L backcross mice, demonstrated that the gene behaves as a simple Mendelian co-dominant. (C) 1998 Academic Press.

Relative dispersions of intra-albumin transit times across rat and elasmobranch perfused livers, and implications for intra- and inter-species scaling of hepatic clearance using microsomal data

It is recognized that vascular dispersion in the liver is a determinant of high first-pass extraction of solutes by that organ. Such dispersion is also required for translation of in-vitro microsomal activity into in-vivo predictions of hepatic extraction for any solute. We therefore investigated the relative dispersion of albumin transit times (CV2) in the livers of adult and weanling rats and in elasmobranch livers. The mean and normalized variance of the hepatic transit time distribution of albumin was estimated using parametric non-linear regression (with a correction for catheter influence) after an impulse (bolus) input of labelled albumin into a single-pass liver perfusion. The mean +/- s.e. of CV2 for albumin determined in each of the liver groups were 0.85 +/- 0.20 (n = 12), 1.48 +/- 0.33 (n = 7) and 0.90 +/- 0.18 (n = 4) for the livers of adult and weanling rats and elasmobranch livers, respectively. These CV2 are comparable with that reported previously for the dog and suggest that the CV2 Of the liver is of a similar order of magnitude irrespective of the age and morphological development of the species. It might, therefore, be justified, in the absence of other information, to predict the hepatic clearances and availabilities of highly extracted solutes by scaling within and between species livers using hepatic elimination models such as the dispersion model with a CV2 of approximately unity.

Polyinosinic acid and polycationic liposomes attenuate the hepatic clearance of circulating plasmid DNA

DNA that enters the circulation is rapidly cleared both by tissue uptake and by DNase-mediated degradation. In this study, we have examined the uptake of linear plasmid DNA in an isolated perfused liver model and following intra-arterial administration to rats. We found that the DNA was rapidly taken up by the isolated perfused liver without degradation. The single-pass extraction ratio was 0.76 +/- 0.05, the mean transit time was 15.3 +/- 3.6 s, and the volume of distribution was 0.29 +/- 0.07 ml/g. Hepatic uptake was saturable and was inhibited by polyinosinic acid or polycationic liposomes but not by condensation of the DNA with polylysine. When the linear plasmid DNA was administered in vivo, plasma half-life was 3.1 +/- 0.2 min, volume of distribution was 670 +/- 85 ml/kg, and clearance was 32 +/- 4 min. Coadministration of cationic liposomes decreased the volume of distribution to 180 +/- 28 ml/kg as well as the half-life (2.6 +/- 0.2 min). By contrast, polyinosinic acid significantly increased the circulating half-life (7.7 +/- 0.5 min), decreased the volume of distribution (95 +/- 17 ml/kg), and partially inhibited DNA degradation. When administered along with the liposomes and the polyinosinic acid, the distribution of plasmid-derived radioactivity decreased in the liver and increased in most other peripheral tissues. This study shows that pharmacological manipulation of the uptake and degradation of DNA can alter its distribution and clearance in vivo. These results may be useful in optimizing gene delivery procedures for in vivo gene therapy.

Mucociliary clearance in patients with chronic asthma: Effects of beta(2) agonists

Chronic asthma is characterized by airway inflammation, mucus hypersecretion and impaired mucociliary clearance (MCC). We investigated baseline MCC and the acute effect of terbutaline in chronic asthmatics with sputum production while on long-term treatment with salmeterol in combination with inhaled corticosteroids (ICS). MCC was measured at baseline and in response to 1 mg terbutaline (or placebo) on three visits over 80 min in 16 asthmatics (52 +/- 13 years of age). Subjects who had greater than 10% absolute increase in MCC above baseline and placebo, after terbutaline, were categorized in group A and subjects who had less than 10% in group B. In group A subjects (n = 6), MCC increased from 23.7 +/- 4.0% at baseline to 43.7 +/- 4.9% with terbutaline (P < 0.0001) and to 34.4 +/- 5.7% with placebo (P < 0.01). In group B subjects (n = 10), MCC remained similar: 11.3 +/- 3.2% at initial baseline, 12.0 +/- 3.2% with terbutaline and 7.3 +/- 3.0% with placebo (P > 0.05). Group B subjects withdrew from all beta(2) agonists for a week and MCC was remeasured. After withdrawal, baseline MCC (7.0 +/- 1.8%) was similar to the initial baseline value (P > 0.1) and MCC with terbutaline (15.8 +/- 4.9%) was greater than baseline (P < 0.005) but remained abnormal in most subjects. Baseline percentage predicted FEV1 and FEF25-75% were 77.3 +/- 7.2 and 41.7 +/- 5.6 in group A and 59.9 +/- 8.1 and 29.5 +/- 8.4 in group B subjects, respectively. MCC was impaired in most of these asthmatics with persistent airway obstruction and sputum production, despite regular treatment with ICS and salmeterol. In addition, there was little or no stimulation of MCC acutely after terbutaline in most of these asthmatics.

Variation of Patterns of Malocclusion by Site of Pharyngeal Obstruction in Children

Objective: To correlate the type of dental occlusion and the type of pharyngeal lymphoid tissue obstruction in children. Design: Cross-sectional study. Setting: Ambulatory ear, nose, and throat clinic of Faculdade de Medicina da Universidade de Sao Paulo. Patients: One hundred fourteen children aged 3 to 12 years presenting with mouth breathing and snoring due to tonsil and/or adenoid enlargement. Interventions: Oroscopy and nasal fiber pharyngoscopy complemented by lateral head radiography to diagnose the type of obstruction, and clinical examination to evaluate the dental occlusion. Main Outcome Measures: Tonsil and adenoid obstruction (classified from grades 1-4) and sagittal, transverse, and vertical evaluation of dental occlusion. Results: Obstructive enlargement of both tonsils and adenoids was detected in 64.9% of the sample; isolated enlargement of the adenoids, in 21.9%; isolated enlargement of the palatine tonsils, in 7.0%; and nonobstructive tonsils and adenoids, in 6.1%. All types of pharyngeal obstruction were related to a high prevalence of posterior crossbite (36.8%). Statistically significant association was found between sagittal dental occlusion and the site of lymphoid tissue obstruction (P = .02). A higher rate of class II relationship (43.2%) was detected in the group with combined adenoid and tonsil obstructive enlargement. Isolated tonsil obstruction showed a higher rate of class III relationship (37.5%). Conclusions: Different sites of obstruction of the upper airway due to enlarged lymphoid tissue are associated with different types of dental malocclusion. Findings are relevant to orthodontic and surgical decision making in these mouth-breathing patients.