Relations between physiologic parameters and pulse transit time during loaded breathing

Pulse transit time (PTT) is a non-invasive measure, defined as time taken for the pulse pressure waves to travel from the R-wave of electrocardiogram to a selected peripheral site. Baseline PTT value is known to be influenced by physiologic variables like heart rate (HR), blood pressure (BP) and arterial compliance (AC). However, few quantitative data are available describing the factors which can influence PTT measurements in a child during breathing. The aim of this study was to investigate the effects of changes in breathing efforts on PTT baseline and fluctuations. Two different inspiratory resistive loading (IRL) devices were used to simulate loaded breathing in order to induce these effects. It is known that HR can influence the normative PTT value however the effect of HR variability (HRV) is not well-studied. Two groups of 3 healthy children ( 0.05) HR changes during all test activities. Results showed that HRV is not the sole contributor to PTT variations and suggest that changes in other physiologic parameters are also equally important. Hence, monitoring PTT measurement can be indicative of these associated changes during tidal or increased breathing efforts in healthy children.

Gastrointestinal transit in the common brushtail possum measured by gamma scintigraphy

This paper reports an example of the application of pharmaceutical technology to wildlife management, specifically the design of an oral delivery system for the common brushtail possum in New Zealand. Designing an oral delivery system requires a knowledge of the time taken for particulates to reach target sites within the gastrointestinal tract (GIT). The transit time for fluid and indigestible particles of two different size ranges was determined in the common brushtail possum (Trichosurus vulpecula). Technetium-labelled (Tc-99m) anion exchange resin particles (75-125 or 500-700 mu m diameter) or solution (Tc-99m-labelled diethylenetriamine pentaacetic acid, Tc-99m-DTPA) was administered orally. At predetermined times after dosing (3, 6, 12, 24 or 32 h), the distribution of radioactivity throughout excised gastrointestinal tracts was determined by gamma scintigraphy. The transit profile was similar for the three formulations investigated. Unlike other closely related hindgut fermenting marsupials, there was no evidence to support the presence of a colonic separating mechanism in the common brushtail possum. Gastrointestinal transit was independent of body mass, gender and time of day that the dose is given. To target the hindgut for oral delivery of protein and peptide biocontrol agents, the formulation Would need to protect the bioactive for approximately 12 h prior to release. (c) 2005 Elsevier B.V. All rights reserved.

Variability in time delay between two models of pulse oximeters for deriving the photoplethysmographic signals

Pulse oximetry is commonly used as an arterial blood oxygen saturation (SaO(2)) measure. However, its other serial output, the photoplethysmography (PPG) signal, is not as well studied. Raw PPG signals can be used to estimate cardiovascular measures like pulse transit time (PTT) and possibly heart rate (HR). These timing-related measurements are heavily dependent on the minimal variability in phase delay of the PPG signals. Masimo SET (R) Rad-9 (TM) and Novametrix Oxypleth oximeters were investigated for their PPG phase characteristics on nine healthy adults. To facilitate comparison, PPG signals were acquired from fingers on the same hand in a random fashion. Results showed that mean PTT variations acquired from the Masimo oximeter (37.89 ms) were much greater than the Novametrix (5.66 ms). Documented evidence suggests that I ms variation in PTT is equivalent to I mmHg change in blood pressure. Moreover, the PTT trend derived from the Masimo oximeter can be mistaken as obstructive sleep apnoeas based on the known criteria. HR comparison was evaluated against estimates attained from an electrocardiogram (ECG). Novametrix differed from ECG by 0.71 +/- 0.58% (p < 0.05) while Masimo differed by 4.51 +/- 3.66% (p > 0.05). Modem oximeters can be attractive for their improved SaO(2) measurement. However, using raw PPG signals obtained directly from these oximeters for timing-related measurements warrants further investigations.

Treatment delays in paediatric dento-alveolar trauma at a tertiary referral hospital

Background: Paediatric dento-alveolar trauma is a common event. Delays in treatment can have adverse effects on long term outcomes and the aim of this study was to quantify the treatment delays in paediatric dento-alveolar trauma in a tertiary referral hospital. Methods: All cases of paediatric dento-alveolar trauma over a two-year period from July 2000 to June 2002 were identified and the charts were reviewed retrospectively. All children presenting the emergency department with dento-alveolar trauma within 48 hours of injury during the time period were included. Results: Forty-three patients were identified. The average age was 5.51 years, though there was a bias towards one and two year olds. Males were injured 1.5 times more frequently than females. There was an average delay of 9.6 hours between injury and treatment for all patients. Transit time from outside practitioners to hospital and waiting times in hospital made up the greatest delays. Children injured an average of 2.37 teeth and only 14 per cent were uncomplicated crown fractures. Conclusions: Children who present to children's hospitals for treatment of dento-alveolar trauma have more severe injuries than those treated elsewhere. They have large but potentially reducible delays between injury and treatment.

Food choice in Siganus fuscescens: influence of macrophyte nutrient content and availability

Using multiple-choice feeding experiments, the selection of six species of macrophytes by the herbivorous rabbitfish Siganus fuscescens was examined. The rabbitfish showed distinct food choice in the laboratory; however, selection of macrophytes by S. fuscescens was not related to their absolute nutrient content (nitrogen, carbon, energy and ash free dry mass). Nutrient assimilation estimates showed that the macrophytes which were most preferred were those that S. fuscescens assimilated best. In S. fuscescens, the macrophytes that were preferred passed through the gut significantly faster than the less preferred species. Gut transit time had a significant effect on the absolute value of a food item in terms of net nutrient gain per unit time. This study showed that food value could be inferred from the absolute nutrient content of the macrophytes. Thus both the ability to assimilate nutrients as well as the absolute nutrient content of macrophytes must be quantified when assessing food value. (C) 2004 The Fisheries society of the British Isles.

A model to study intestinal and hepatic metabolism of propranolol in the dog

A model to investigate hepatic drug uptake and metabolism in the dog was developed for this study. Catheters were placed in the portal and hepatic veins during exploratory laparotomy to collect pre- and posthepatic blood samples at defined intervals. Drug concentrations in the portal vein were taken to reflect intestinal uptake and metabolism of an p.o. administered drug (propranolol), while differences in drug and metabolite concentrations between portal and hepatic veins reflected hepatic uptake and metabolism. A significant difference in propranolol concentration between hepatic and portal veins confirmed a high hepatic extraction of this therapeutic agent in the dog. This technically uncomplicated model may be used experimentally or clinically to determine hepatic function and metabolism of drugs that may be administered during anaesthesia and surgery.

Disposition kinetics of propranolol isomers in the perfused rat liver

The aim of this study was to define the determinants of the linear hepatic disposition kinetics of propranolol optical isomers using a perfused rat liver. Monensin was used to abolish the lysosomal proton gradient to allow an estimation of propranolol ion trapping by hepatic acidic vesicles. In vitro studies were used for independent estimates of microsomal binding and intrinsic clearance. Hepatic extraction and mean transit time were determined from outflow-concentration profiles using a nonparametric method. Kinetic parameters were derived from a physiologically based pharmacokinetic model. Modeling showed an approximate 34-fold decrease in ion trapping following monensin treatment. The observed model-derived ion trapping was similar to estimated theoretical values. No differences in ion-trapping values was found between R(+)- and S(-)- propranolol. Hepatic propranolol extraction was sensitive to changes in liver perfusate flow, permeability-surface area product, and intrinsic clearance. Ion trapping, microsomal and nonspecific binding, and distribution of unbound propranolol accounted for 47.4, 47.1, and 5.5% of the sequestration of propranolol in the liver, respectively. It is concluded that the physiologically more active S(-)- propranolol differs from the R(+)- isomer in higher permeability-surface area product, intrinsic clearance, and intracellular binding site values.

Predictive regression equations and clinical uses of peripheral pulse timing characteristics in children

Studies have shown that increased arterial stiffening can be an indication of cardiovascular diseases like hypertension. In clinical practice, this can be detected by measuring the blood pressure (BP) using a sphygmomanometer but it cannot be used for prolonged monitoring. It has been established that pulse wave velocity (PWV) is a direct measure of arterial stiffening but its usefulness is hampered by the absence of non-invasive techniques to estimate it. Pulse transit time (PTT) is a simple and non-invasive method derived from PWV. However, limited knowledge of PTT in children is found in the present literature. The aims of this study are to identify independent variables that confound PTT measure and describe PTT regression equations for healthy children. Therefore, PTT reference values are formulated for future pathological studies. Fifty-five Caucasian children (39 male) aged 8.4 +/- 2.3 yr (range 5-12 yr) were recruited. Predictive equations for PTT were obtained by multiple regressions with age, vascular path length, BP indexes and heart rate. These derived equations were compared in their PWV equivalent against two previously reported equations and significant agreement was obtained (p < 0.05). Findings herein also suggested that PTT can be useful as a continuous surrogate BP monitor in children.

Age-related factors that confound peripheral pulse timing characteristics in Caucasian children

Characteristics obtained from peripheral pulses can be used to assess the status of cardiovascular system of subjects. However, nonintrusive techniques are preferred when prolonged monitoring is required for their comfort. Pulse transit time ( PTT) measurement has showed its potentials to monitor timing changes in peripheral pulse in cardiovascular and respiratory studies. In children, the common peripheries used for these studies are fingers or toes. Presently, there is no known study conducted on children to investigate the possible physiologic parameters that can confound PTT measure at these sites. In this study, PTT values from both peripheral sites were recorded from 55 healthy Caucasian children ( 39 male) with mean age of 8.4 +/- 2.3 years ( range 5 - 12 years). Peripheries' path length, heart rate, systolic blood pressure, diastolic blood pressure ( DBP) and mean arterial pressure ( MAP) were measured to investigate their contributions to PTT measurement. The results reveal that PTT is significantly related to all parameters ( P< 0.05), except for DBP and MAP. Age is observed to be the dominant factor that affects PTT at both peripheries in a child. Regression equations for PTT were derived for measuring from a finger and toe, ( 6.09 age + 189.2) ms and ( 6.70 age + 243.0) ms, respectively.

Testing the reliability of a new ultrasonic cardiac output monitor, the USCOM, by using aortic flowprobes in anesthetized dogs

We have used an animal model to test the reliability of a new portable continuous-wave Doppler ultrasonic cardiac output monitor, the USCOM. In six anesthetized dogs, cardiac output was measured with a high-precision transit time ultrasonic flowprobe placed on the ascending aorta. The dogs' cardiac output was increased with a dopamine infusion (0-15 mug (.) kg(-1) (.) min(-1)). Simultaneous flowprobe and USCOM cardiac output measurements were made. Up to 64 pairs of readings were collected from each dog. Data were compared by using the Bland and Altman plot method and Lin's concordance correlation coefficient. A total of 319 sets of paired readings were collected. The mean (+/-SD) cardiac output was 2.62 +/- 1.04 L/min, and readings ranged from 0.79 to 5.73 L/min. The mean bias between the 2 sets of readings was -0.01 L/min, with limits of agreement (95% confidence intervals) of -0.34 to 0.31 L/min. This represents a 13% error. In five of six dogs, there was a high degree of concordance, or agreement, between the 2 methods, with coefficients >0.9. The USCOM provided reliable measurements of cardiac output over a wide range of values. Clinical trials are needed to validate the device in humans.

Screening of obstructive and central apnoea/hypopnoea in children using variability: A preliminary study

Aim: Polysomnography (PSG) is the current standard protocol for sleep disordered breathing (SDB) investigation in children. Presently, there are limited reliable screening tests for both central (CE) and obstructive (OE) respiratory events. This study compared three indices, derived from pulse oximetry and electrocardiogram ( ECG), with the PSG gold standard. These indices were heart rate (HR) variability, arterial blood oxygen de-saturation (SaO(2)) and pulse transit time (PTT). Methods: 15 children (12 male) from routine PSG studies were recruited (aged 3 - 14 years). The characteristics of the three indices were based on known criteria for respiratory events (RPE). Their estimation singly and in combination was evaluated with simultaneous scored PSG recordings. Results: 215 RPE and 215 tidal breathing events were analysed. For OE, the obtained sensitivity was HR (0.703), SaO(2) (0.047), PTT (0.750), considering all three indices (0) and either of the indices (0.828) while specificity was (0.891), (0.938), (0.922), (0.953) and (0.859) respectively. For CE, the sensitivity was HR (0.715), SaO(2) (0.278), PTT (0.662), considering all indices (0.040) and either of the indices (0.868) while specificity was (0.815), (0.954), (0.901), (0.960) and (0.762) accordingly. Conclusions: Preliminary findings herein suggest that the later combination of these non-invasive indices to be a promising screening method of SDB in children.

Hepatic pharmacokinetics of propranolol in rats with adjuvant-induced systemic inflammation

Systemic inflammation is known to affect drug disposition in the liver. This study sought to relate and quantitate changes in hepatic pharmacokinetics of propranolol with changes in hepatic architecture and physiology in adjuvant-treated rats. Transmission electron microscopy was used to assess morphological changes in mitochondria and lysosomes of adjuvant-treated rat livers. The disposition of propranolol was assessed in the perfused rat liver using the multiple indicator dilution technique. Hepatic extraction and mean transit time were determined from outflow-concentration profiles using a nonparametric method. Kinetic parameters were derived from a two-phase physiologically based organ pharmacokinetic model. Possible relationships were then explored between the changes in hepatic drug disposition and cytochrome P-450 activity and iron concentration. Adjuvant treatment induced the appearance of mitochondrial inclusions/tubularization and irregularly shaped lysosomes in rat livers. Livers from adjuvant-treated rats had (relative to normal) significantly higher alpha(1)-acid glycoprotein (orosomucoid) and iron tissue concentrations but lower cytochrome P-450 content. The hepatic extraction, metabolism, and ion trapping of propranolol were significantly impaired in adjuvant-treated rats and could be correlated with altered iron store and cytochrome P-450 activity. It is concluded that adjuvant-induced systemic inflammation alters hepatocellular morphology and biochemistry and consequently influences hepatic disposition of propranolol.

A double-blind, randomized, placebo-controlled trial of macrolide in the treatment of chronic rhinosinusitis

Objectives: The antiinflammatory effect of macrolide antibiotics has been well-established, as has their role in the treatment of certain disorders of chronic airway inflammation. Several studies have suggested that long-term, low-dose macrolides may be efficacious in the treatment of chronic rhinosinusitis; however, these studies have lacked a control group. To date, this effect has not been tested in a randomized, placebo-controlled study. Method: The authors conducted a double-blind, randomized, placebo-controlled clinical trial on 64 patients with chronic rhinosinusitis. Subjects received either 150 mg roxithromycin daily for 3 months or placebo. Outcome measures included the Sinonasal Outcome Test-20 (SNOT-20), measurements of peak nasal inspiratory flow, saccharine transit time, olfactory function, nasal endoscopic scoring, and nasal lavage assays for interleukin-8, fucose, and a2-macroglobulin. Results. There were statistically significant improvements in SNOT-20 score, nasal endoscopy, saccharine transit time, and IL-8 levels in lavage fluid (P < .05) in the macrolide group. A correlation was noted between improved outcome measures and low IgE levels. No significant improvements were noted for olfactory function, peak nasal inspiratory flow, or lavage levels for fucose and a2-macroglobulin. No improvement in any outcome was noted in the placebo-treated patients. Conclusion: These findings suggest that macrolides may have a beneficial role in the treatment of chronic rhinosinusitis, particularly in patients with low levels of IgE, and supports the in vitro evidence of their antiinflammatory activity. Additional studies are required to assess their place in clinical practice.

Use of regression equation of peripheral pulse timing characteristics to predict hypertension in children

Studies have shown that an increase in arterial stiffening can indicate the presence of cardiovascular diseases like hypertension. Current gold standard in clinical practice is by measuring the blood pressure of patients using a mercury sphygmomanometer. However, the nature of this technique is not suitable for prolonged monitoring. It has been established that pulse wave velocity is a direct measure of arterial stiffening. However, its usefulness is hampered by the absence of techniques to estimate it non-invasively. Pulse transit time (PTT) is a simple and non-intrusive method derived from pulse wave velocity. It has shown its capability in childhood respiratory sleep studies. Recently, regression equations that can predict PTT values for healthy Caucasian children were formulated. However, its usefulness to identify hypertensive children based on mean PTT values has not been investigated. This was a continual study where 3 more Caucasian male children with known clinical hypertension were recruited. Results indicated that the PTT predictive equations are able to identify hypertensive children from their normal counterparts in a significant manner (p < 0.05). Hence, PTT can be a useful diagnostic tool in identifying hypertension in children and shows potential to be a non-invasive continual monitor for arterial stiffening.