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Biomedical subjects

R R Kirby

Publications and source records attributed to R R Kirby.

At least 19 recordsLinked to original sources
PubMed2000

Cloning and primary structure of putative cytosolic and mitochondrial malate dehydrogenase from the mollusc Nucella lapillus (L.).

The evolutionary history of the malate dehydrogenase (MDH) gene family [NAD-dependent MDH; EC 1.1.1.37 and NAD(P)-dependent MDH; EC 1.1.1.82] has received much attention. MDHs have also featured extensively as electrophoretic markers in population genetics and evolutionary ecology, and in many cases, intraspecific variation in MDH has been correlated with environmental variables. However, while the amino acid residues essential for MDH function are known, no studies have examined intraspecific nucleotide variation despite evidence indicating that natural selection may be operating on this locus. This study presents two sets of degenerate oligonucleotide PCR primers to facilitate the cloning of cytosolic MDH (cMDH) and mitochondrial MDH (mMDH) from a broad range of animals (cMDH) and animals and plants (mMDH). These primers were used to obtain putative cMDH and mMDH cDNAs from the mollusc Nucella lapillus. The N. lapillus cMDH cDNA was found to encode a putative cMDH protein of 334aa and 36kDa, while the mMDH cDNA encoded a putative mature mMDH protein of 315aa and 33kDa. The putative amino acid sequences of the two compartmentalised N. lapillus MDHs are presented and compared to other known MDH sequences.

Amino Acid Sequence↗
PubMed2000

An ancient transpecific polymorphism shows extreme divergence in a multitrait cline in an intertidal snail (Nucella lapillus (L.)).

Clines in intraspecific genetic variation are frequently associated with an environmental transition. Here, divergence among nucleotide sequences of two nuclear loci, cytosolic and mitochondrial malate dehydrogenase (cMDH and mMDH, respectively), is described, in a multitrait cline over a distance of ca. 3 km where shell phenotype, allozyme, mitochondrial DNA haplotype, and centric fusion (Robertsonian translocations) frequencies covary with temperature and humidity and change abruptly in a continuous population of the dog-whelk (Nucella lapillus), a common intertidal snail of the north temperate Atlantic. Protein electrophoresis has already shown two alleles of mMDH varying from fixation of one allele to near fixation of the other, whereas cMDH appears to be monomorphic. The results of this study show a striking disparity in nucleotide sequence divergence among alleles at the two loci, with extreme molecular differentiation in one of them. Four alleles of cMDH were found to have nucleotide and amino acid sequence divergences of 0.4% and 0.3%, respectively. In contrast, the two mMDH cDNA alleles differed by 23% and 20% at the nucleotide and amino acid levels, respectively. Analysis of a 91-bp partial nucleotide sequence of mMDH from Nucella freycineti, the closest relative of N. lapillus, revealed two similar alleles and indicated that the divergence in mMDH in N. lapillus represents an ancient transpecific polymorphism in these Nucella. Together with earlier studies on variation in N. lapillus, it is argued that the polymorphism in mMDH and the clines in N. lapillus represent the presence of two persistent coadapted gene complexes, multitrait coevolving genetic solutions to environmental variation, which may presently enable this snail to exploit a diverse environment successfully.

Alleles↗
PubMed1999

Noncardiogenic pulmonary edema associated with protamine administration during coronary artery bypass graft surgery.

Protamine sulfate is the only agent approved to reverse heparin-induced anticoagulation. As with any other drug, protamine has the potential to cause adverse effects that range from mild hypotension to potentially fatal events, such as noncardiogenic pulmonary edema (NCPE) and catastrophic pulmonary vasoconstriction. We report a case of NCPE after the administration of protamine to a patient undergoing coronary artery bypass graft surgery and discuss the diagnosis and management of this severe adverse event.

Aged↗
PubMed1997

The monitoring of mechanically ventilated patients.

Mechanical ventilation may adversely affect cardiovascular stability, pulmonary function, and airway anatomy. Hemodynamic monitoring needs to be adequate to determine the effects of mechanical ventilation on hemodynamic status in a given patient, effects that represent the complex interactions of airway pressure with venous return, right heart function, and left heart function. Monitoring of the adequacy of pulmonary gas exchange and intrinsic and extrinsic work of breathing can decrease adverse or inadequate effects of mechanical ventilation on respiratory function. Finally, monitoring cuff pressure will decrease the incidence of tracheal damage during mechanical ventilation.

Humans↗
PubMed1995

Breathing frequency and pattern are poor predictors of work of breathing in patients receiving pressure support ventilation.

OBJECTIVE: To evaluate the relationships between directly measured work of breathing (WOB) and variables of the breathing pattern commonly used at the bedside to infer WOB for intubated, spontaneously breathing patients treated with pressure support ventilation (PSV). DESIGN: In vivo measurements of the WOB were obtained on a consecutive series of adults. Breathing frequency (f), tidal volume (VT), the index of rapid, shallow breathing (f/V T), the duration of respiratory muscle contraction expressed as the ratio of inspiratory time over total respiratory cycle time (TI/TTOT), and a breathing pattern score (applied to approximately 50% of the patients) which ranks f, VT, sternocleidomastoid muscle activity, substernal retraction, and abdominal paradox on a scale were variables of the breathing pattern were also measured. The greater the breathing pattern score, the lower the WOB and vice versa. SETTING: Surgical ICUs in two university teaching hospitals. PATIENTS: Sixty-seven adults (42 men and 25 women, aged 20 to 78 years) who had acute respiratory failure from various etiologies were studied. All patients were breathing spontaneously receiving continuous positive airway pressure and PSV. INTERVENTIONS: Intraesophageal pressure (indirect measurement of intrapleural pressure) was measured with an esophageal balloon integrated into a nasogastric tube. VT was obtained by positioning a flow sensor between the "Y" piece of breathing circuit and the endotracheal tube. Data from these measurements were directed to a bedside respiratory monitor (Bicore; Allied Healthcare Products; Riverside, Calif) that calculates WOB using the Campbell diagram. Patients received PSV at levels deemed reasonable to unload the respiratory muscles. All measurements were obtained after 15 to 20 min at each level of PSV, averaged over 1 min, and then variables of the breathing pattern were regressed with directly measured values for WOB. RESULTS: All breathing pattern variables poorly predicted WOB as evidenced by the low values for the coefficients of determination (r2). Breathing frequency correlated positively with WOB (r = 0.47, p < 0.001) and predicted or explained only 22% (r2 = .22) of the variance in WOB. VT correlated negatively and f/VT and TI/TTOT each correlated positively with WOB. However, these variables predicted only 20 to 27% of the variance in WOB. The breathing pattern score correlated negatively with WOB and predicted only 43% of the variance in WOB. A prediction model taking all variables into consideration using multiple regression analysis predicted only 50% of the variance in WOB; thus, it too was a poor to moderate predictor of WOB. CONCLUSION: Our data reveal that WOB should be measured directly because variables of the breathing pattern commonly used at the bedside appear to be inaccurate and misleading inferences of the WOB. The clinical implication of these findings involves the traditional and empirical practice of titrating PSV based on the breathing pattern. We do not imply that the patient's breathing pattern should be ignored, nor undermine its importance, for it provides useful diagnostic information. It appears, however, that relying primarily on the breathing pattern alone does not provide enough information to accurately assess the respiratory muscle workload. Using the breathing pattern as the primary guideline for selecting a level of PSV may result in inappropriate respiratory muscle workloads. A more comprehensive strategy is to employ WOB measurements and the breathing pattern in a complementary manner when titrating PSV in critically ill patients.

Adult↗
PubMed1994

Components of the work of breathing and implications for monitoring ventilator-dependent patients.

OBJECTIVES: a) To discuss the components of the work of breathing using an established physiologic model (Campbell diagram); b) to describe the requirements of a monitor to measure work; and c) to discuss the implications and relevance for assessing the work of breathing of ventilator-dependent patients. DATA SOURCES: Relevant articles from the medical and physiologic literature are referenced, as well as the authors' experience. STUDY SELECTION: Identified (by authors) laboratory and clinical research establishing the need and physiologic importance for correctly measuring the work of breathing. DATA EXTRACTION: A physiologic model of the various components of the work of breathing is used in conjunction with data from published literature. SYNTHESIS: Diagrams of increasing complexity based on the Campbell diagram depict the physiologic elastic and resistive work of breathing for the lungs and chest wall under normal and abnormal conditions. Decreases in compliance and increases in airways resistance are associated with increases in elastic and resistive work, respectively. A modification of the Campbell diagram to include an additional area depicting the imposed work of the breathing apparatus is suggested; i.e., the additional resistive load imposed on the respiratory muscles by the endotracheal tube, breathing circuit, and the ventilator's demand-flow system during spontaneous breathing. Increases in physiologic and/or imposed work result in respiratory muscle loading, predisposing to increases in oxygen consumption and the development of fatigue and hypercapnia. Measuring work of breathing by integrating the area of the esophageal pressure-volume loop alone underestimates the work of breathing relative to the Campbell diagram and, therefore, should not be used. Because the site of pressure measurement and mode of ventilation influence measurements of the work of breathing as well as compliance, clinicians should be aware of these factors when interpreting measurements. Monitors that are used in clinical practice to assess the work of breathing should be able to measure pressure at the airway opening (between the Y-piece of the breathing circuit and the endotracheal tube), at the carinal end of the endotracheal tube, and in the esophagus (inference of intrapleural pressure); as well as measure flow rate and volume at the airway opening; and calculate the various components of the work of breathing based on the Campbell diagram. CONCLUSIONS: Accurate measurement of physiologic and imposed work performed by the patient are essential to assess the afterload on the respiratory muscles, diagnose specific work of breathing abnormalities, and monitor the effects of interventions to mitigate respiratory muscle loading. Work of breathing data are useful in formulating objective guidelines for setting the ventilator appropriately to optimize respiratory muscle loads, e.g., selecting an appropriate amount of pressure support ventilation to decrease the work of breathing to a specific level.

Airway Resistance↗
PubMed1994

Partially and totally unloading respiratory muscles based on real-time measurements of work of breathing. A clinical approach.

OBJECTIVE: To evaluate the clinical feasibility of using real-time measurements of work of breathing obtained at the bedside with a portable, commercially available respiratory monitor as an objective and quantifiable guideline for appropriately setting pressure support ventilation (PSV) to partially and totally unload the respiratory muscles in patients with respiratory failure. DESIGN: In vivo measurements of work of breathing were performed on a consecutive series of patients after applying incremental levels of PSV. SETTING: University teaching hospital in a surgical ICU. PATIENTS: Thirty adults (18 men and 12 women, ages 20 to 77 years) who had acute respiratory failure were studied. All patients had an endotracheal or a tracheostomy tube in place and were breathing spontaneously, receiving continuous positive airway pressure and PSV. INTERVENTIONS: Intraesophageal pressure (indirect measurement of intrapleural pressure) was measured with an esophageal balloon catheter positioned in the mid- to lower-third of the esophagus. Tidal volume was obtained by positioning a flow sensor between the "Y" piece of the breathing circuit and the endotracheal or tracheostomy tube. Airway pressure was measured from a catheter attached to the flow sensor. Data from these measurements were directed to the respiratory monitor (CP-100, Bicore Monitoring Systems) which calculates work of breathing performed by the patient using the Campbell diagram. Work of breathing performed by the ventilator to inflate the respiratory system was calculated by the monitor by integrating the change in airway pressure and tidal volume. Initially, the level of PSV was set to 0 cm H2O and work measurements were obtained. Pressure support ventilation was then increased until the work performed by the patient decreased to a range of 0.3 to 0.6 J/L, which corresponds to a normal range for physiologic work of breathing (ie, partial respiratory muscle unloading), and then until the work decreased to 0 J/L (ie, total respiratory muscle unloading). RESULTS: Work performed by the patient varied inversely (r = -0.83; p < 0.001) and work performed by the ventilator varied directly with the level of PSV (r = 0.94; p < 0.001). Work performed by the patient was 1.5 +/- 0.3 J/L at zero pressure support ventilation and decreased significantly to 0.50 +/- 0.1 J/L (p < 0.05) as the level of PSV was increased to 18 +/- 7 cm H2O. The respiratory muscles were partially unloaded under these conditions. Patient work decreased to 0 J/L and ventilator work increased when the muscles were totally unloaded at a PSV level of 31 +/- 8 cm H2O. CONCLUSION: We propose an objective and goal-oriented clinical approach for using PSV by directly measuring the work of breathing performed by the patient with an easy to operate, bedside respiratory monitor and then applying pressure support ventilation to decrease the work to appropriate levels. Partially or totally shifting the workload from the respiratory muscles to the ventilator is appropriate under specific clinical conditions.

Acute Disease↗
PubMed1993

Imposed work of breathing and methods of triggering a demand-flow, continuous positive airway pressure system.

OBJECTIVES: To compare the inspiratory imposed work of breathing during spontaneous ventilation with continuous positive airway pressure using three methods of triggering "ON" the demand-flow system of a ventilator: a) conventional pressure triggering with the pressure measuring/triggering site inside the ventilator on the exhalation limb of the breathing circuit; b) tracheal pressure triggering from the tracheal or carinal end of the endotracheal tube; and c) flow-by (flow triggered) triggering. DESIGN: Multitrial tests under simulated clinical conditions using a mechanical lung model. SETTING: A research laboratory at a university medical center. INTERVENTIONS: Spontaneous breathing with continuous positive airway pressure, at peak sinusoidal inspiratory flow rate demands of 30, 60, and 90 L/min with sizes 6, 7, 8, and 9 mm internal diameter endotracheal tubes at each flow rate during conventional pressure triggering, tracheal pressure triggering, and flow-by. MEASUREMENTS AND MAIN RESULTS: Pressures were measured at the tracheal end of the endotracheal tube, "Y" piece of the breathing circuit, and inside the ventilator on the exhalation limb of the breathing circuit. Volume measured between the endotracheal tube and lung model and pressure measured at the tracheal end of the endotracheal tube were integrated to generate pressure-volume (work) loops to calculate the inspiratory imposed work of the total breathing apparatus (i.e., endotracheal tube, breathing circuit, and ventilator). Significantly (p < .05) greater decreases in pressure during spontaneous inhalation were measured for all methods of triggering at the tracheal end of the endotracheal tube than at the Y piece or inside the ventilator. Inspiratory-imposed work was significantly lower during tracheal pressure triggering compared with conventional pressure triggering and flow-by under most conditions. For example, with a 7-mm internal diameter endotracheal tube at a peak inspiratory flow rate demand of 60 L/min, imposed work was 382% and 315% lower, respectively, during tracheal pressure triggering compared with the conventional pressure triggering and flow-by triggering methods. Under all conditions, inspiratory imposed work was lower during flow-by triggering compared with conventional pressure triggering. The smaller the internal diameter of the endotracheal tube and the greater the peak inspiratory flow rate demand, the greater the inspiratory imposed work of breathing for all methods of triggering. Under all conditions, inspiratory-imposed work was significantly greater at a peak inspiratory flow rate demand of 90 L/min than at 60 L/min, and at a peak inspiratory flow rate demand of 60 L/min than at 30 L/min. CONCLUSIONS: An endotracheal tube is a resistor in the breathing apparatus over which a pressure decrease must be developed by the patient in order to inhale spontaneously. An endotracheal tube, therefore, imposes substantial resistance and work. The results indicate that the pressure measuring/triggering site for a ventilator's demand-flow system should be at the tracheal or carinal end of an endotracheal tube so as to effectively decrease the resistance of the endotracheal tube, thus, decreasing the patient's work of breathing.

Airway Resistance↗
PubMed1993

Decreasing imposed work of the breathing apparatus to zero using pressure-support ventilation.

OBJECTIVES: To apply pressure-support ventilation with the goal of decreasing the imposed work of the breathing apparatus (endotracheal tube, breathing circuit tubing, and the ventilator's demand-flow system) to zero and to evaluate a clinical method of measuring the imposed work of breathing. DESIGN: A prospective evaluation of adult and pediatric patients receiving mechanical ventilatory support. SETTING: A surgical and a pediatric intensive care unit in a university hospital. PATIENTS: Fifteen patients (11 adult and four pediatric), who were diagnosed with acute respiratory failure from various etiologies, and who were intubated and spontaneously breathing, received continuous positive airway pressure and pressure-support ventilation. MEASUREMENTS AND MAIN RESULTS: Imposed work of the breathing apparatus was calculated by integrating pressure measured at the tracheal end of the endotracheal tube from a narrow air-filled catheter and the change in volume from a miniature pneumotachograph (flow sensor) positioned between the "Y" piece of the breathing circuit and the endotracheal tube. Pressure and volume signals were directed to a computerized, portable respiratory monitor (Bicore Monitoring Systems) that provides real-time display of the pressure-volume (work) loops and calculation of the imposed work. Imposed work was measured at 0 cm H2O pressure-support ventilation, and then incremental levels of pressure-support ventilation were applied until the imposed work decreased to zero. Imposed work decreased in a quadratic fashion after incremental levels of pressure-support ventilation (r = -.83 [r2 = .69]; p < .001). At pressure-support ventilation level of 0 cm H2O, the imposed work was 0.60 +/- 0.17 joule/L. At mean pressure-support ventilation levels of 13.5 +/- 4.8 cm H2O, imposed work decreased to 0 joule/L. CONCLUSIONS: Ideally, the imposed work of the breathing apparatus should be zero to decrease the afterload on the ventilatory muscles and, thus, the patient's work of breathing. Eliminating the imposed work is achieved using appropriate levels of pressure-support ventilation. We describe an easily applied, practical method of measuring imposed work using a commercially available, portable, bedside respiratory monitor. We recommend that all patients diagnosed with respiratory failure and compromised pulmonary mechanics and who are intubated and breathing spontaneously, receive at least a minimal level of pressure-support ventilation that results in zero breathing apparatus-imposed work of breathing.

Acute Disease↗
PubMed1992

Site of pressure measurement during spontaneous breathing with continuous positive airway pressure: effect on calculating imposed work of breathing.

OBJECTIVE: To describe the importance of measuring pressure at the tracheal end of the endotracheal tube during spontaneous breathing with continuous positive airway pressure in order to correctly assess: a) the changes in airway pressure and b) the work imposed by the breathing apparatus. DESIGN: Multitrial tests under simulated clinical conditions using a mechanical lung model. SETTING: A research laboratory at a university medical center. INTERVENTIONS: Spontaneous breathing with continuous positive airway pressure, at peak sinusoidal inspiratory flow-rate demands of 30 and then 60 L/min with sizes 6, 7, 8, and 9 mm internal diameter endotracheal tubes at each flow rate. MEASUREMENTS AND MAIN RESULTS: Pressure, flow rate, and inhaled and exhaled volumes, during simulated spontaneous ventilation with continuous positive airway pressure were measured. Pressure was measured alternately at the "Y" piece of the breathing tubing of the continuous positive airway pressure system and at the tracheal end of the endotracheal tube to calculate the work imposed by the breathing circuit, endotracheal tube, and the total breathing apparatus. Greater changes in pressure and work were measured at the tracheal end of the endotracheal tube than at the "Y" piece of the breathing tubing for all test conditions. For example, at a peak inspiratory flow-rate demand of 30 L/min when pressures measured at the tracheal end of endotracheal tubes were compared with pressures measured at the "Y"piece, the total work imposed by the breathing apparatus increased by approximately 145% with a 6-mm tube, 95% with a 7-mm tube, 50% with an 8-mm tube, and 40% with a 9-mm tube (p less than .05). Measuring pressure at the "Y" piece of the tubing results in significant underestimations of the changes in pressure and the work imposed, especially when the endotracheal tube has a small internal diameter and/or when the peak inspiratory flow-rate demand is high. CONCLUSIONS: The results indicate that pressure should be measured as close to the patient's airway as possible, i.e., at the tracheal end of the endotracheal tube, rather than using the traditional approach of measuring pressure and assessing work at the inspiratory or expiratory limbs, or "Y" piece of the breathing tubing.

Humans↗
PubMed1991

Airway pressure release ventilation during acute lung injury: a prospective multicenter trial.

OBJECTIVE: To evaluate the feasibility of airway pressure release ventilation (APRV) in providing ventilatory support to patients with acute lung injury of diverse etiology and mild-to-moderate severity. DESIGN: Prospective, multicenter, nonrandomized crossover trial. SETTING: ICUs in six major referral hospitals. PATIENTS: Fifty adult patients with respiratory failure requiring mechanical ventilation and positive end-expiratory airway pressure. INTERVENTIONS: After optimization of continuous positive airway pressure (CPAP), conventional ventilation and APRV were administered sequentially for 30 mins. During APRV, the CPAP level and airway pressure release level were adjusted to prevent hypoxemia, while the degree of ventilatory support was adjusted by altering the frequency of pressure release. MEASUREMENTS AND MAIN RESULTS: Circulatory and ventilatory pressures, arterial blood gases and pH, heart rate, and respiratory rate were measured. Alveolar ventilation was augmented adequately in 47 of 50 patients by APRV. Adjustment of APRV required an increase in mean CPAP from 13 +/- 3 (SD) to 21 +/- 9 cm H2O and a release pressure of 6 +/- 5 cm H2O. This airway pressure pattern produced a mean airway pressure comparable to that pressure achieved during conventional ventilation. Failure of APRV in three patients could be attributed to an inadequate level of CPAP or an inadequate APRV rate. While maintaining oxygenation of arterial blood and circulatory function, APRV allowed a substantial (55 +/- 17%; p less than .0001) reduction in peak airway pressure compared with conventional positive pressure ventilation adjusted to deliver a comparable or lower level of ventilatory support. CONCLUSIONS: APRV is a feasible alternative to conventional mechanical ventilation for augmentation of alveolar ventilation in patients with acute lung injury of mild-to-moderate severity.

Adult↗