Biomedical subjects

A Nahum

Publications and source records attributed to A Nahum.

At least 55 records · Page 3Linked to original sources

PubMed1994

Conformal radiotherapy at the Royal Marsden Hospital (UK).

Conformal radiotherapy seeks to allow increased intensity of radiation by reducing the volume of normal tissues within the treatment volume. Techniques have developed secondary to improvements in three-dimensional imaging and accessible treatment technology is based on computer-controlled multileaf collimators to create an irregular radiation beam shape. Preliminary clinical work in the Royal Marsden Hospital seeks to quantify the toxicity reduction achievable by conformal techniques in the context of a prospective randomized pelvic radiotherapy trial which has now recruited 240 patients. The data accumulated during this trial will allow comparison of conformal and conventional radiotherapy and also analysis of the impact of dose and volume of a particular organ on both acute and late toxicity. Assessments have revealed that conformal techniques reduced significantly the treatment volume of normal tissues, e.g. by a mean of 54% for rectum and 42% for bladder. However, a relationship between volume and acute toxicity has not been established. Late toxicity is currently being analysed. Dose escalation trials in thoracic and in pelvic tumours are planned.

Humans↗

PubMed1994

Effect of a nasogastric tube on esophageal pressure measurement in normal adults.

We studied the correspondence between fluctuations of esophageal pressure measured before and after placement of a nasogastric (NG) tube in six normal volunteers. Flow, airway pressure, and esophageal pressure data from at least 20 breaths were recorded in seven ventilatory conditions in two body postures: 0 degree (supine) and 60 degrees (upright). The conditions studied included normal quiet breathing, added resistance, reduced compliance, increased frequency, increased tidal volume, continuous positive airway pressure, and volume-cycled ventilation with positive pressure. During recording with the NG tube in place, the subject targeted the same tidal volume (VT), respiratory rate, and inspiratory time fraction (TI/TTOT) recorded before NG tube placement. A computer program selected for analysis only those recorded breaths with and without an NG tube that were "matched" within 5 percent for both VT and TI. We calculated average VT, TI, and esophageal pressure fluctuation (delta Pes) for the matched breaths from each subject during every condition. The delta Pes values with and without NG tube were not statistically different in any tested condition (p > 0.05). Our data indicate that the presence of an NG tube does not invalidate the accuracy of delta Pes measurements made using a well-positioned balloon catheter in the tested conditions.

Adult↗

PubMed1993

Effect of catheter flow direction on CO2 removal during tracheal gas insufflation in dogs.

Tracheal gas insufflation (TGI) improves the efficiency of CO2 elimination by replacing CO2 in the anatomic dead space proximal to the catheter tip with fresh gas during expiration. Turbulence generated by gas exiting the catheter tip may also contribute to alveolar ventilation. To separate distal (turbulence-related) and proximal (washout of dead space) effects of TGI, we compared the efficacy of a straight and an inverted catheter during continuous and expiratory TGI in six mechanically ventilated dogs. We reasoned that the inverted catheter cannot improve CO2 elimination from more distal conducting airways. During continuous TGI with the straight catheter, arterial PCO2 (PaCO2) decreased significantly from baseline (without TGI) of 56 +/- 10 Torr to 38 +/- 8, 36 +/- 8, and 35 +/- 8 Torr at catheter flow rates (Vcath) of 5, 10, and 15 l/min, respectively. For the same conditions, PaCO2 was always higher (P < 0.001) with the inverted catheter (42 +/- 10, 41 +/- 10, and 41 +/- 10 Torr). PaCO2 was lower with the straight (40 +/- 9 Torr) than with the inverted catheter (44 +/- 10 Torr, P < 0.001) during TGI delivered only during expiration at a Vcath of 10 l/min. End-expiratory lung volume relative to baseline increased during continuous, but not during expiratory, TGI and was significantly greater with the straight than with the inverted catheter (P < 0.0001). Our data confirm that the primary mechanism of TGI is expiratory washout of the proximal anatomic dead space but also suggest a minor contribution of turbulence beyond the tip of the straight catheter.

Animals↗

PubMed1993

Tracheal gas insufflation augments CO2 clearance during mechanical ventilation.

A technique that improves the efficiency of alveolar ventilation should decrease the pressure required and reduce the potential for lung injury during mechanical ventilation. Alveolar ventilation may be improved by replacing a portion of the anatomic dead space with fresh gas via an intratracheal catheter. We studied the effect of intratracheal gas insufflation as an adjunct to volume cycled ventilation in eight sedated, paralyzed patients with a variety of lung disorders. Continuous flows of 2, 4, and 6 L/min were delivered through a catheter positioned 1 or 10 cm above the carina. Carbon dioxide production, inspiratory minute ventilation, and peak and mean airway pressures did not change over the range of flows tested. PaCO2 and dead space volume/tidal volume decreased significantly as joint functions of catheter flow and position (p < 0.001). The highest catheter flow (6 L/min) and most distal catheter position (1 cm above the carina) were the most effective combination tested, averaging a 15% reduction in PaCO2 (range 9 to 23%). Certain characteristics of the expiratory capnogram were helpful in predicting the observed reduction in PaCO2. Tracheal gas insufflation may eventually prove a useful adjunct to a pressure-targeted strategy of ventilatory management (in either volume-cycled or pressure controlled modes), particularly when the total dead space is heavily influenced by its anatomic component.

Adult↗

PubMed1993

Modes of tracheal gas insufflation. Comparison of continuous and phase-specific gas injection in normal dogs.

Tracheal gas insufflation (TGI) improves the efficiency of CO2 elimination accomplished by conventional mechanical ventilation, primarily by reducing the anatomic (series) dead space volume. Dead space proximal to the catheter tip can be reduced by two methods. Fresh gas introduced at the carinal level during inspiration may effectively "bypass" the upper airway. Alternatively, proximal dead space can be "washed out" with fresh gas during expiration to reduce CO2 rebreathing. We examined these two modes of TGI-aided dead space reduction in nine paralyzed normal dogs receiving conventional mechanical ventilation and compared these results to those obtained with a catheter that delivered fresh gas continuously at the same flow rate, thereby accomplishing both bypass and washout. Total inspired tidal volume and cycling frequency were held constant. Differences in CO2 elimination efficiency among the TGI modes were flow dependent. Continuous catheter flow at 5 or 10 L/min reduced PaCO2 and physiologic dead space fraction (VD/VT) more than either proximal bypass or end-expiratory washout (p < 0.001). At the same catheter flow settings expiratory washout tended to improve VD/VT more than did inspiratory bypass. Under the conditions tested, constant tracheal insufflation of fresh gas improves alveolar ventilation by mechanisms that include, but are not limited to, a functional reduction in the dead space proximal to the catheter tip.

Analysis of Variance↗

PubMed1992

Lung mechanics and gas exchange during pressure-control ventilation in dogs. Augmentation of CO2 elimination by an intratracheal catheter.

Increased awareness of pressure-related injury to the alveolar-capillary interface has renewed interest in modes of ventilation that limit alveolar distention such as pressure-controlled ventilation (PCV). We examined respiratory system mechanics and gas exchange during PCV in six dogs. Our data conformed to the predictions of our single-compartment mathematical model of respiratory dynamics during PCV (J Appl Physiol 1989; 67:1081-92). For a fixed pressure (Pset) and inspiratory time fraction (Tl/Ttot) (15 cm H2O and 0.3, respectively), minute ventilation (VE) reached a well-defined plateau as frequency (f) increased from 10 to 50 breaths/min and tidal volume (VT) fell progressively. Concomitantly, the physiologic dead-space fraction (VD/VT) increased from 0.50 +/- 0.04 to 0.85 +/- 0.04, and arterial PCO2 (PaCO2) rose from 39 +/- 4 to 76 +/- 12 mm Hg. At a fixed combination of frequency, applied pressure, and Tl/Ttot (40 breaths/min, 15 cm H2O, and 0.3), VE did not change when we introduced fresh gas continuously from an intratracheal catheter. However, PaCO2 and VD/VT fell progressively as catheter flow increased from zero to 14 L/min (60 +/- 12 to 40 +/- 12 mm Hg and 0.83 +/- 0.03 to 0.25 +/- 0.14 mm Hg, respectively). We conclude that during PCV at a fixed Pset and Tl/Ttot increasing frequency caused VT to fall and VE to reach a plateau. Declining VT was associated with a rise in PaCO2 because of a subsequent fall in alveolar ventilation. Insufflating fresh gas by an intratracheal catheter increased alveolar ventilation and improved CO2 elimination by washing out the anatomic dead space.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Tracheal gas insufflation during pressure-control ventilation. Effect of catheter position, diameter, and flow rate.

In the setting of acute lung injury, ventilatory strategies that adjust minute ventilation (VE) to achieve eucapnia often lead to alveolar rupture or damage. Tracheal gas insufflation (TGI) reduces the VE requirements of conventional mechanical ventilation by decreasing the effective dead-space fraction (VD/VT) of each breath. We studied the effect of catheter flow rate (Vcath) and position as well as catheter tip diameter and configuration on CO2 elimination during TGI-augmented pressure-controlled ventilation (PCV) in normal dogs. We studied three catheter positions (1, 5, and 10 cm above the carina) at Vcath of 2, 5, and 10 L/min (n = 6). When the catheter tip was positioned 1 cm above the carina, PaCO2 decreased significantly from a baseline (PCV alone) of 67 +/- 10 mm Hg to 52 +/- 11, 43 +/- 9, and 32 +/- 7 mm Hg (p < 0.05) at Vcath of 2, 5, and 10 L/min, respectively. For the same Vcath values, positioning the catheter tip 10 cm above the carina increased PaCO2 to 54 +/- 15, 46 +/- 12, and 40 +/- 11 mm Hg. Advancing the catheter tip 2 cm below the carina did not improve PaCO2 significantly (n = 3). At a catheter position of 1 cm above the carina and a Vcath of 10 L/min, changing the luminal inner diameter (1.5 versus 3.0 mm) or tip configuration (open tip versus occluded tip with two side holes) of the catheter did not change PaCO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Differential activation of mixed venous and arterial neutrophils in patients with sepsis syndrome and acute lung injury.

Neutrophil (PMN) functions, such as production of toxic oxygen (O2) metabolites, adherence, and chemotactic properties, are modified during local tissue inflammation and sepsis. We hypothesized that PMN would be primed during their transit through injured tissue beds, which in turn can lead to modulation or retention of the primed PMN by downstream tissues like the lungs. We tested this hypothesis by measuring the transpulmonary gradient of hydrogen peroxide (H2O2) production by zymosan-activated PMN. We examined the mixed venous to arterial difference in H2O2(delta H2O2) produced by zymosan-activated PMN in septic patients without lung infiltrates, patients with lung injury, and a control group of patients undergoing elective surgery or coronary catheterization. Septic patients had higher mixed venous H2O2/10(6) PMN, whereas lung injury patients had higher arterial H2O2/10(6) PMN. The control group had the same H2O2/10(6) PMN in mixed venous and arterial blood. The delta H2O2 in septic, lung injury, and control groups were 0.35 +/- 0.22, -0.31 +/- 0.48, and -0.01 +/- 0.04 nmol H2O2/10(6) PMN, respectively. The mixed venous to arterial H2O2 gradient distinguished septic patients from the control and lung injury patients (p less than 0.05). Our results are consistent with the hypothesis that in septic patients PMN are primed in the periphery and downregulated or sequestered in the lung, and in lung injury patients PMN are primed in the lung and sequestered in the periphery. Alternatively, neutrophil-endothelial interactions may downregulate toxic O2 metabolite production by PMN during their transit through microvascular beds.

Adult↗

PubMed1990

Effect of sodium azide on hydrogen peroxide production by zymosan-activated human neutrophils.

Stimulated neutrophils (PMNs) produce large quantities of superoxide anion, which is the precursor for hydrogen peroxide (H2O2). We developed a new fluorimetric assay to measure the H2O2 released by zymosan A-activated PMNs utilizing the oxidation of p-hydroxyphenylacetic acid by H2O2 to its fluorescent dimer in the presence of horseradish peroxidase. Zymosan-activated PMNs isolated from nine healthy volunteers and 20 patients with acute hypoxemic respiratory failure (AHRF) released after 90 min 2.3 +/- 0.3 and 2.4 +/- 1.3 nmol H2O2/10(6) PMNs, respectively. Inhibition of the heme enzymes by 1.0 mM sodium azide (NaN3) increased the H2O2 production to 21.6 +/- 4.4 nmol H2O2/10(6) PMNs in the control group (P less than 0.001), and to 22.5 +/- 14.7 nmol H2O2/10(6) PMNs in patients with AHRF (P less than 0.001). Incubation temperature, room temperature or 37 degrees C, did not change the total amount of H2O2 produced after 90 min by zymosan-activated PMN. Addition of NaN3 improved both the sensitivity and reproducibility of the measurement of H2O2 and allowed detection of H2O2 released by PMNs with coefficients of variation of less than 5% at PMN concentrations as low as 0.1 x 10(6) cells/ml. The amount of H2O2 released by activated PMNs did not distinguish healthy controls from patients with AHRF.

Adult↗

PubMed1990

Pathogenesis of pulmonary edema associated with intracisternal endotoxin in dogs.

To examine the role of central nervous system injury in the pathogenesis of pulmonary edema, we injected Escherichia coli endotoxin (5 mg/kg) into the cisterna magna of six dogs (group E) and compared, over 4 h, both the pulmonary edema and cerebrospinal fluid (CSF) abnormalities with those in six control dogs (group C). In group E, intracisternal endotoxin raised intracranial pressure from 21 +/- 6 to 38 +/- 8 cmH2O (P less than 0.001), CSF total protein from 18 +/- 6 to 54 +/- 19 mg/dl (P less than 0.001), and CSF malondialdehyde from 0.12 +/- 0.11 to 0.61 +/- 0.35 nmol/ml (P less than 0.05); all were unchanged in group C. When the pulmonary wedge pressure was maintained at 10 mmHg by fluid infusion, extravascular thermal volume in group E increased from 7.2 +/- 1.2 to 12.0 +/- 2.7 ml/kg (P less than 0.005) at 4 h when the excised lungs weighed 13.6 +/- 1.5 g/kg; in group C, extravascular thermal volume did not increase, and the excised lungs weighed less (10.8 +/- 1.3 g/kg, P less than 0.05) than those in group E. The dry weights of the lungs were not different between groups, and the alveolar lining fluid-to-plasma albumin ratio in both groups remained low, 0.1-0.2. Fluid infusion in group E (9.2 +/- 2.9 liters) caused colloid oncotic pressure to decrease 4.5 +/- 2.8 mmHg; colloid oncotic pressure fell less (0.8 +/- 1.9 mmHg, P less than 0.001) in group C as less fluid (2.2 +/- 1.5 liters, P less than 0.001) was required to maintain pulmonary wedge pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Measurement of hydrogen peroxide in plasma and blood.

Measurement of the oxygen metabolite hydrogen peroxide (H2O2) in biological fluids such as plasma could be of interest because it might indicate participation of toxic oxygen species in tissue injury. Recently several reports claimed to measure H2O2 using spectrophotometric and high pressure liquid chromatographic (HPLC) techniques that utilize oxidation of a substrate to a product by a peroxidase. In such a system it is crucial to perform two control experiments to verify whether the measured substance is H2O2. The specificity of the assay for H2O2 should be checked with catalase, and the degradation of H2O2 or inhibition of the assay system by the sample should be checked by determining the recovery of exogenously added H2O2. We performed both types of controls for HPLC and spectrophotometric determinations of H2O2 in plasma and blood. Our results indicate that contrary to previous reports in the literature the measured substance(s) in plasma or blood is not H2O2. Moreover, quantitative measurements of H2O2 in plasma or blood by HPLC was unreliable due to the irreversible binding of H2O2 to the column surface.

Animals↗

PubMed1989

Alveolar pressure inhomogeneity and gas exchange during constant-flow ventilation in dogs.

Analysis of momentum transfer between inflow jets and resident gas during constant-flow ventilation (CFV) predicts inhomogeneity of alveolar pressures (PA) and volume, which might account for specific ventilation-variance in the lung. Using alveolar needles to measure pressures (PA) during CFV in eight anesthetized dogs with wide thoracotomy, we observed random dispersion of PA among lobes of up to 12.5 cmH2O. Within each lobe, the PA dispersion was up to 10 cmH2O at CFV of 90 l/min; when flow decreased, PA at all sites decreased, as did the intralobar dispersion. These pressure differences were not observed during conventional mechanical ventilation (CMV). During CFV with room air, dogs were hypoxemic [arterial PO2 (Pao2) 54 +/- 15 Torr] and the venous admixture (Qva/QT) was 50 +/- 15%. When inspiratory O2 fraction was increased to 0.4, Pao2 increased to 172 +/- 35 Torr and Qva/QT dropped to 13.5 +/- 8.4%, confirming considerable ventilation-perfusion (VA/Q) variance not observed during CMV. We conclude that momentum transfer between the inflow stream and resident gas caused inhomogeneities of alveolar pressures, volumes, and ventilation responsible for VA/Q variance and hypoxemia during CFV. Conceivably, the abnormal ventilation distribution is minimized by collateral ventilation and forces of interdependence between regions of high and low alveolar pressures. Momentum transfer also predicted the mucosal damage observed on histological evaluation of the bronchial walls near the site of inflow jet impact.

Animals↗

PubMed1989

Increased hydrogen peroxide in the expired breath of patients with acute hypoxemic respiratory failure.

Acute hypoxemic respiratory failure (AHRF) can result from diverse lung insults. Toxic oxygen metabolites have been implicated in this clinical condition and in animal models of pulmonary edema. Hydrogen peroxide (H2O2), an oxygen metabolite, mediates tissue injury. We measured H2O2 levels by a spectrophotometric technique in the breath condensate of 68 mechanically ventilated patients; 13 patients with normal lungs undergoing elective surgery had no such detectable levels of H2O2. Fifty-five patients in the ICU meeting criteria for the adult respiratory distress syndrome (ARDS) had a higher concentration of H2O2 in the expired breath condensate than ICU patients without pulmonary infiltrates (2.34 +/- 1.15 vs 0.99 +/- 0.72 mumol/L, p less than 0.005). This marker had a sensitivity of 87.5 percent and a specificity of 81.3 percent in separating the two patient populations. Patients with AHRF and focal pulmonary infiltrates who did not meet criteria for ARDS also had higher concentrations of H2O2 (2.45 +/- 1.55 mumol/L) than patients without pulmonary infiltrates (p less than 0.001). No difference was observed between the expired H2O2 concentrations of patients with ARDS or patients with focal pulmonary infiltrates. Patients with brain injury or sepsis tended to have higher levels of H2O2 regardless of lung pathology. Increased levels of H2O2 are detected in the expired breath of ICU patients with focal lung infiltrates and in ARDS patients, which is consistent with the hypothesis that oxygen metabolites participate in the pathogenesis of ARDS and other forms of AHRF.

Breath Tests↗

PubMed1988

Benefits expected from simple conformal radiotherapy in the treatment of pelvic tumours.

In 20 patients with invasive bladder cancer suitable for radical radiotherapy, a simple conformal planning technique has been compared with conventional beam arrangements in terms of normal tissue sparing. The median treatment volume for the group was reduced from 2275 to 1416 cm3 by the introduction of conformal planning. More specifically, in 13/20 patients (65%) the percentage volume of rectum irradiated to 90% of the isocentric dose was reduced by more than 30%, although the extent of rectal sparing varied greatly between patients. Overall, conformal planning appeared to be less successful at reducing the volume of large and small bowel irradiated to high dose. However, the data suggest that considerable benefit can be expected for those patients most at risk of morbidity by virtue of high bowel volumes included within the treatment length. A randomised trial is now being set up to determine the clinical impact of this planning technique in terms of reduced bowel morbidity.

Humans↗

PubMed1988

Pressure, flow, and density relationships in airway models during constant-flow ventilation.

Adequate CO2 elimination and normal arterial PCO2 levels can be maintained in dogs during apnea by delivering a continuous flow of inspired gas at high flow rate (1-3 l.min-1.kg-1) through tubes placed in the main-stem bronchi. However, during constant-flow ventilation (CFV) the mean alveolar pressure is increased, causing increased lung volume despite low pressures in the trachea. We hypothesized that the increased dynamic alveolar pressures during CFV were due to momentum transfer from the high-velocity jet stream to resident gas in the lung. To test this, we simulated CFV in straight tubes and in a branched airway model to determine whether changes in gas flow rate (V), gas density (rho), and tube diameter (D) altered the pressure difference (delta P) between alveoli and airway opening in a manner consistent with that predicted by conservation of momentum. Momentum analysis predicts that delta P should vary with V2, whereas measurements yielded a dependence of V1.69 in branched tubes and V1.9 in straight tubes. Substitution of heliox (80% He-20% O2) for air significantly reduced lung hyperinflation during CFV. As predicted by momentum transfer, delta P varied with rho 1.0. Momentum analysis also predicts that delta P should vary with D-2.0, whereas measurements indicated a dependence on D-2.02. The influence of V and rho on depth of penetration of the jet down the airway was explored in a straight tube model by varying the flow rate and gas used. The influence of geometry on penetration was measured by changing the ratio of jet-to-airway tube diameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Models, Biological↗

PubMed1987

Ventilation-perfusion inequality during constant-flow ventilation.

Previous work by Lehnert et al. (J. Appl. Physiol. 53:483-489, 1982) has demonstrated that adequate alveolar ventilation can be maintained during apnea in anesthetized dogs by delivering a continuous stream of inspired ventilation through cannulas aimed down the main-stem bronchi. Because an asymmetric distribution of ventilation might introduce ventilation-perfusion (VA/Q) inequality, we compared gas exchange efficiency in nine anesthetized and paralyzed dogs during constant-flow ventilation (CFV) and conventional ventilation (intermittent positive-pressure ventilation, IPPV). Gas exchange was assessed using the multiple inert gas elimination technique. During CFV at 3 l X kg-1 X min-1, lung volume, retention-excretion differences (R-E*) for low- and medium-solubility gases, and the log standard deviation of blood flow (log SD Q) increased, compared with the findings during IPPV. Reducing CFV flow rate to 1 l X kg-1 X min-1 at constant lung volume improved R-E* and log SD Q, but significant VA/Q inequality compared with that at IPPV remained and arterial PCO2 rose. Comparison of IPPV and CFV at the same mean lung volume showed a similar reversible deterioration in gas exchange efficiency during CFV. We conclude that CFV causes significant VA/Q inequality which may be due to nonuniform ventilation distribution and a redistribution of pulmonary blood flow.

Animals↗

PubMed1986

Chamber-dependent wall correction factors in dosimetry.

The calculation of the response of ionisation chambers to different photon beam qualities used in radiotherapy requires electron stopping-power data. These data have recently been revised and are used here to derive a consistent set of correction factors for ionisation chambers of different wall and build-up cap composition. Theoretically derived parameters km and katt which relate the exposure calibration of an ionisation chamber to the absorbed dose to the air of the cavity, are compared with the experimentally derived product kmkatt showing generally good agreement but also significant discrepancies for plastic-walled chambers with inner graphite coatings. A table of km values is given for a large number of commercial ionisation chambers. The new stopping-power data are also used to evaluate the wall-dependent correction factor (pwall) that enters into the determination of the absorbed dose to water in photon beams, results being given as a function of the quality of the beam. Our theoretical calculations of pwall are consistent with existing experimental data.

Cobalt Radioisotopes↗

PubMed1985

[Not Available].

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History of Pharmacy↗