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Biomedical subjects

J D Marks

Publications and source records attributed to J D Marks.

At least 109 records · Page 6Linked to original sources
PubMed1987

Differential inhibition of the diaphragm and posterior cricoarytenoid muscles induced by transient hypertension across sleep states in intact cats.

Arterial pressure was transiently elevated by intravenous infusion of phenylephrine in intact, freely moving cats during sleep and waking states to determine pressure effects on diaphragmatic and laryngeal abductor EMG activity. Transient hypertension caused respiratory cycle duration to increase and integrated EMG area to decrease for several breaths in both the diaphragm and posterior cricoarytenoid, the integrated inspiratory area of which decreased to a greater extent than did that of the diaphragm. Cycle duration increases resulted from increases in expiratory duration. Expiratory duration of the posterior cricoarytenoid initially increased proportionately more than that of the diaphragm, causing a transient phase disassociation between that upper airway muscle and diaphragmatic timing. This disassociation disappeared after several breaths. Changes in posterior cricoarytenoid expiratory duration and integrated inspiratory area were sleep state-dependent: area decreases were greatest in rapid eye movement sleep; expiratory duration increases were greatest in quiet sleep. Neural mechanisms underlying laryngeal abductor activity are sleep state-dependent and appear to be affected more than diaphragmatic mechanisms by baroreceptor stimulation.

Animals↗
PubMed1986

Poor correlation between pulmonary arterial wedge pressure and left ventricular end-diastolic volume after coronary artery bypass graft surgery.

The authors studied 12 surgical patients in the intensive care unit post coronary artery bypass graft surgery and ten nonsurgical patients in the coronary care unit with chronic heart failure to determine the usefulness of the pulmonary arterial wedge pressure as an indicator of left ventricular preload. Left ventricular end diastolic volume was derived from concomitant determination of ejection fraction (gated blood pool scintigraphy) and stroke volume (determined from thermodilution cardiac output). In the nonsurgical patients, there was a significant correlation between changes in pulmonary arterial wedge pressure and left ventricular end-diastolic volume (P less than 0.05, r = 0.57). In the 12 patients studied during the first few hours after surgery, there was a poor correlation between changes in pulmonary wedge pressure (range = 4-32 mmHg) and left ventricular end-diastolic volume (range = 25-119 ml/m2), and a poor correlation between pulmonary arterial wedge pressures and stroke work index. In contrast, there was a good correlation between left ventricular end-diastolic volume and stroke work index. The poor correlation between the pulmonary arterial wedge pressure and left ventricular end-diastolic volume was not explained by changes in systemic or pulmonary vascular resistance. The altered ventricular pressure-volume relationship may reflect acute changes in ventricular compliance in the first few hours following coronary artery bypass graft surgery. While measurement of pulmonary arterial wedge pressure remains valuable in clinical management to avoid pulmonary edema, it cannot reliably be used as an index of left ventricular preload while attempting to optimize stroke volume in patients immediately following coronary artery bypass graft surgery.

Aged↗
PubMed1985

Respiratory inhibition induced by transient hypertension during sleep in unrestrained cats.

The effects of transient blood pressure elevation, induced by intravenous injection of phenylephrine, were studied in drug-free, unrestrained cats during sleep and waking. Transient hypertension evoked an increase in respiratory cycle duration (Ttot), an effect which was most prominent during quiet sleep. Transient hypertension evoked no overall change in inspiratory duration (Tdi) during any sleep-waking state, although reduction of diaphragmatic EMG amplitude was observed. Thus, the ratio of diaphragmatic activity time to total respiratory cycle duration (Tdi/Ttot) was decreased following blood pressure elevation. Apneic episodes occasionally occurred, and these occurrences were more frequent during sleep states. Apneas induced during quiet sleep were often associated with transient or sustained arousal.

Animals↗
PubMed1985

Inspiratory work with and without continuous positive airway pressure in patients with acute respiratory failure.

To compare the effects of continuous positive airway pressure (CPAP) with those of ambient end-expiratory pressure (T-tube) on lung mechanics and blood gas exchange, transpulmonary pressure (Ptp), tidal volume (VT), respiratory frequency, and arterial oxygen and carbon dioxide tensions were measured in 16 spontaneously breathing patients recovering from acute respiratory failure. These variables were measured during breathing through a T-tube; with 18, 12, and 6 cmH2O CPAP; and again during breathing through a T-tube. During all levels of CPAP, mean effective lung compliance (Ceff) was higher and mean total pulmonary power during inspiration lower than during breathing through a T-tube before CPAP (P less than 0.05). The data obtained at the level of CPAP producing maximum Ceff (optimum CPAP) were grouped and compared with values obtained during breathing through a T-tube. Mean total pulmonary power of inspiratory muscles during breathing through a T-tube before CPAP (0.7 +/- 0.14 kg X m X min-1) decreased during optimum CPAP (0.44 +/- 0.07 kg X m X min-1) and increased during breathing through a T-tube after CPAP (0.63 +/- 0.12 kg X m X min-1). Mean VT was higher (557 +/- 63 ml vs. 474 +/- 47 ml) and frequency lower (17.5 +/- 1.6 breaths/min vs. 22.5 +/- 2.5 breaths/min) during optimum CPAP than during breathing through a T-tube before CPAP, and inspiratory time was significantly longer. Mean minute ventilation was also lower during optimum CPAP (8.7 +/- 0.6 1/min) than during breathing through a T-tube (9.6 +/- 0.8 1/min); Paco2 did not change significantly. Mean alveolar-to-arterial oxygen pressure difference decreased significantly during optimum CPAP. The authors conclude that CPAP, when adjusted to the appropriate levels, improves lung mechanics in patients recovering from acute respiratory failure. Continuous positive airway pressure reduces total pulmonary power during inspiration and at the same time improves oxygen and carbon dioxide exchange. In these respects, it is preferable to breathing through a T-tube without CPAP.

Acute Disease↗
PubMed1985

Effect of increases in lung volume on clearance of aerosolized solute from human lungs.

To study the effect of increases in lung volume on solute uptake, we measured clearance of 99mTc-diethylenetriaminepentaacetic acid (Tc-DTPA) at different lung volumes in 19 healthy humans. Seven subjects inhaled aerosol (1 micron activity median aerodynamic diam) at ambient pressure; clearance and functional residual capacity (FRC) were measured at ambient pressure (control) and at increased lung volume produced by positive pressure [12 cmH2O continuous positive airway pressure (CPAP)] or negative pressure (voluntary breathing). Six different subjects inhaled aerosol at ambient pressure; clearance and FRC were measured at ambient pressure and CPAP of 6, 12, and 18 cmH2O pressure. Six additional subjects inhaled aerosol at ambient pressure or at CPAP of 12 cmH2O; clearance and FRC were determined at CPAP of 12 cmH2O. According to the results, Tc-DTPA clearance from human lungs is accelerated exponentially by increases in lung volume, this effect occurs whether lung volume is increased by positive or negative pressure breathing, and the effect is the same whether lung volume is increased during or after aerosol administration. The effect of lung volume must be recognized when interpreting the results of this method.

Aerosols↗
PubMed1984

State-dependent alteration of respiratory cycle timing by stimulation of the central nucleus of the amygdala.

The effect of electrical stimulation of the amygdaloid central nucleus (ACE) on respiration was studied in unanesthetized, unrestrained cats during sleep-waking states. Single 0.5-ms 500-microA constant-current pulses delivered to the ACE at various points on the respiratory cycle, produced a transient inspiratory effort which summated with ongoing inspiratory activity and reduced inspiratory time. Stimulus pulses delivered during the expiratory phase resulted in an earlier shift to inspiration. Repetitive single pulse stimuli delivered to the ACE at a rate slightly faster than the spontaneous respiratory cycle during the alert state, were capable of 'entraining' respiration at the stimulus frequency. This entrainment disappeared in quiet sleep. Atropine, however, which produced synchronous high voltage slow waves and 12-14-Hz EEG spindle activity in the alert cat, did not impair this entrainment. Short (300-500 ms) 100-Hz trains of 0.5-ms pulses to the ACE produced rapid onset, sustained inspiration and a rise in blood pressure in the alert animal. During quiet sleep the response was attenuated but qualitatively similar, and also aroused the animal. Single pulse stimuli, however, were not associated with cardiovascular changes or generalized arousal. These results suggest that the ACE contributes to excitation of the inspiratory cycle, possibly through the large projection of this nucleus to the parabrachial pons.

Amygdala↗
PubMed1984

Sleep states attenuate the pressor response to central amygdala stimulation.

We examined the cardiovascular response to electrical stimulation of the region of the central nucleus of the amygdala during sleep and waking states in the intact cat. Stimulation for 0.5 s produced a profound pressor response in the awake animal. This response was attenuated by quiet sleep and greatly attenuated during REM sleep. The attenuation was present even when the animal aroused from the sleep state in which the stimulus was delivered. The degree of sinus arrhythmia during the bradycardia associated with the hypertensive phase was greater during waking than during quiet sleep. We speculate that REM sleep entails a "functional dissociation" between forebrain and brain stem systems involved in cardiovascular regulation.

Amygdala↗
PubMedDate not supplied

Increased target specificity of anti-HER2 genospheres by modification of surface charge and degree of PEGylation.

Genospheres are cationic lipid-nucleic acid nanoparticles prepared by the assembly of the lipids and nucleic acids from an aqueous/organic liquid monophase that independently dissolves the components, where the resultant particles are homogeneously sized (70-110 nm), with efficiently incorporated and protected DNA. In the present study, we demonstrate pH-dependent modulation of the Genosphere surface charge using pH-titratable lipids. By incorporation of the lipids with titratable anionic or imidazole headgroups, Genospheres with neutral or anionic surface charge at neutral pH were produced and compared for cellular uptake and transfection of a reporter gene (luciferase) in culture of breast cancer cells. The extent of particle-cell association was also studied by fluorescent microscopy and quantified by cytofluorometery. The effects of Genosphere surface modification with poly(ethylene glycol) (molecular weight 2000) at low (0.5 mol %) and high (5 mol %) grafting densities, as well as the effects of HER2-receptor-directed targeting by an internalizable anti-HER2 scFv F5, linked via PEG spacer, were also studied. Inclusion in the Genosphere formulation of pH-titratable lipids CHEMS (cholesteryl hemisuccinate), CHIM (1-(3-(cholesteryloxycarbonylamino)propyl)imidazole), or DSGG (1,2-distearoyl-sn-glycero-3-hemiglutarate) rendered the particles surface-charge neutral or slightly anionic at neutral pH, and cationic at mildly acidic pH, as shown by zeta-potential measurements. In HER2-targeted systems, transfection activity and target specificity with HER2-overexpressing SKBR-3 breast cancer cells were dependent on Genosphere surface charge and PEGylation. The highest target specificity correlated with low cationic charge at neutral pH, while incorporation of 5 mol % PEG-lipid had only minor effects on Genosphere-cell association, internalization, and transfection activity. The implications of this work for potential in vivo applications are discussed.

Antibodies↗
PubMedDate not supplied

Engineering and characterization of a novel fusion protein incorporating B7.2 and an anti-ErbB-2 single-chain antibody fragment for the activation of Jurkat T cells.

The provision of the T-cell costimulatory molecule B7 to tumor cells can be an effective way to trigger a tumor-specific cytolytic T-cell response. One way to provide B7 to tumor cells would be to couple an antitumor antibody directly to B7. Such a molecule should target tumors displaying antigen and provide the costimulatory signal to T cells, resulting in the initiation of an antitumor T-cell response. To this end, a fusion protein was designed that incorporates a single-chain antibody fragment (scFv) to erbB-2 (Her2/neu), an oncogene product overexpressed by 30% to 50% of breast carcinomas, and the ECD of B7-2 (CD86). This fusion protein, expressed and purified from Pichia pastoris, was shown to retain binding activity to both counter receptors, erbB-2 and CD28. The fusion protein was also shown to target erbB-2-positive tumor cells and to deliver a CD28-specific T-cell costimulatory signal. These results suggest that a fusion protein engineered to target tumor cells and signal T cells for activation may be an effective means of cancer immunotherapy. Further studies should be performed to characterize the fusion protein in erbB-2 tumor-bearing mice for in vivo tumor targeting, biodistribution, and efficacy.

Amino Acid Sequence↗
PubMedDate not supplied

Pressure indices of myocardial oxygen consumption during pulsatile ventricular assistance.

Left ventricular (LVP) and intramyocardial (IMP) pressure indices were compared with left ventricular myocardial oxygen consumption (MVO2) during pulsatile ventricular assistance to determine if MVO2 can be predicted under conditions of ventricular support. During five acute anesthetized calf experiments, IMP and LVP were recorded for control and six conditions of support. The assisted conditions were asynchronous and synchronous, 1:1 or 1:2; each control mode with atrial uptake only or combined atrial and ventricular uptake. IMP was measured by implantation of a miniature pressure transducer in the midanteriolateral wall of the left ventricle. MVO2 was determined using the radioactive microsphere blood flow technique and blood gas data. Mean values of peak systolic pressure, maximum dP/dt, and integral of Pdt were calculated for IMP and LVP for each condition. Pressure indicators of left ventricular function were found to correlate well with MVO2 during conditions of pulsatile support.

Animals↗
PubMedDate not supplied

Myocardial mechanics, energetics, and hemodynamics during intraaortic balloon and transvalvular axial flow hemopump support with a bovine model of ischemic cardiac dysfunction.

Unlike the mechanisms of intraaortic balloon pump (IABP) support, the mechanisms by which transvalvular axial flow Hemopump (HP) support benefit dysfunctional myocardium are less clearly understood. To help elucidate these mechanisms, hemodynamic, metabolic, and mechanical indexes of left ventricular function were measured during conditions of control, ischemic dysfunction, IABP support, and HP support. A large animal (calf) model of left ventricular dysfunction was created with multiple coronary ligations. Peak intraventricular pressure increased with HP support and decreased with IABP support. Intramyocardial pressure (an indicator of intramyocardial stress), time rate of pressure change (an indicator of contractility), and left ventricular myocardial oxygen consumption decreased with IABP and HP support. Left ventricular work decreased with HP support and increased with IABP support. During HP support, indexes of wall stress, work, and contractility, all primary determinants of oxygen consumption, were reduced. During IABP support, indexes of wall stress and contractility were reduced and external work increased. These changes were attributed primarily to changes in ventricular preload, and geometry for HP support, and to a reduction in afterload for IABP support. These findings support the hypothesis that both HP and IABP support reduce intramyocardial stress development and the corresponding oxygen consumption, although via different mechanisms.

Animals↗
PubMedDate not supplied

Successful repair of a ventricular assist system percutaneous lead.

A patient with an implanted, electrically powered, ventricular assist device (Thermo Cardiosystems VE HeartMate) experienced a partial break of the percutaneous lead 5 months after implantation. The break (limited to the Silicone rubber tube) occurred at the junction of the lead with the Y-connector to the controller and vent, leaving approximately 5 cm of exposed lead from the skin exit site to the connector. Electronic and pumping functions of the pump continued, but the opening in the lead (which went more that half way around the circumference) prevented the use of pneumatic actuation as a back-up mode for pump operation, and placed the pump at risk for contamination. Repair of the lead without surgical intervention was desirable, with ease of repair and minimal risk to the patient being the top priorities. The use of multiple layers of heat-shrink tubing or external metal stents was ruled out in favor of a three stage repair procedure. The first stage involved the removal of the Dacron velour in-growth material from the lead to expose the underlying Silicone rubber tube. While the opening in the tube was held shut, a coating of medical grade Silicone rubber adhesive was applied to the tube, then wrapped with a woven Dacron mesh, followed by two layers of plastic wrapping material to protect the adhesive. This initial layer was secured by an external stent of tubing with cable ties. After several days to allow for complete curing of the adhesive, the adhesive coating with mesh was repeated. The final step involved a double layer wrap of a 1 mm thick Silicone rubber sheeting with mesh incorporation and adhesive secured in place with cable ties. After completion of the repair and verification of the ability to operate the device with pneumatic actuation, the patient was discharged with no recurrence of the problem after 8 months of weekly follow-up. This experience demonstrates the need to clinically anticipate component repair or replacement without total device replacement in future implantable blood pump systems.

Adhesives↗
PubMedDate not supplied

Conduct of device clinical trials: the need for collaboration in response to a changing health care environment.

Prior to initiating a clinical trial, many issues need to be discussed to insure an adequate understanding of the investigators' and sponsors' limitations, capabilities, and expectations. Many of these issues are addressed in contracts and agreements, the formats for which have evolved over many years. In these documents, issues such as publication rights, access to results, confidentiality, conditions for termination, compensation, and indemnification are covered. However, other essential, although noncontractual issues that reflect upon trends in and the climate of the health care system, need to be discussed. Issues such as the development of collaborative cost-effectiveness studies, public relations plans, content of a cost-benefit analysis, results of other trials, reimbursement strategies, and the development of resources that contribute to the ease, safety, and efficacy of device use. With the increasing expense, oversight, and administrative burden for the conduct and participation in clinical trials, there is a correspondingly greater need for sponsor and investigator communication, collaboration, and risk and cost sharing to ensure the successful outcome of clinical trials today.

Clinical Trials as Topic↗
PubMedDate not supplied

Perioperative mechanical circulatory support for transplantation.

Mechanical circulatory assistance has become a necessary supplement to more conventional means of hemodynamic support as a shortage of donor organs and associated increase in waiting time have contributed to an increased incidence of hemodynamic deterioration in potential transplant recipients. This review summarizes the experience with circulatory support before and after transplantation of the Utah Transplantation Affiliated Hospitals (UTAH) Cardiac Transplant Program and draws conclusions on the efficacy of one program's use of mechanical circulatory support. Between March 1985 and October 1990, 401 patients were accepted for first-time heart transplantation by the UTAH program. One hundred and eighty patients (46%) were supported before transplantation with conventional hemodynamic therapies, 72 patients (18%) with oral enoximone, 96 patients (25%) with intravenous inotropes, and 34 patients (9%) with an intraaortic balloon; nine patients (2%) required centrifugal blood pump circulatory support. Not included in these statistics are 10 patients awaiting transplantation as of October 10, 1990. Thirty-eight candidates (10%) died awaiting transplantation, 329 (84%) received transplantation, and 24 (6%) were removed from the transplantation list for other reasons. Ten patients (3%) required mechanical circulatory support after transplantation with 38% of this group surviving 1 year after after transplantation. No single factor, including either hemodynamic support before transplantation or donor heart ischemic time, was found to be predictive of the need for mechanical circulatory support after transplantation. One-year survival rates after transplantation of patients requiring mechanical circulatory support before transplantation (86%) were not significantly different than for all transplant patients (88%). The experience of the UTAH Cardiac Transplant Program shows that with the judicious use of mechanical circulatory support transplant patients with advanced forms of hemodynamic support can have as equal a probability of survival as patients who undergo elective transplantation.

Adult↗
PubMedDate not supplied

Comparison of microsphere and intraoperative quantitation of bronchial blood flow.

Although significant variation in bronchial blood flow (BBF) has been reported, precise quantitation is difficult because of the small sized vessels and variable anatomy. Ventricular balance is critical to the function of the total artificial heart (TAH), and variation in BBF can alter this balance in the bovine model. Bronchial blood flow was measured in 12 calves by two methods: six by the radioactive labeled microsphere technique (MBBF), and six intraoperatively (IBBF) during cardiopulmonary bypass (CPB). In the MBBF group, BBF ranged from 1.9 ml/kg to 16.0 ml/kg, whereas IBBF varied from 2.6 ml/kg to 10 ml/kg (NS). Cardiac output (CO) was significantly higher (p less than 0.0005) in the MBBF group. Bronchial blood flow in both groups was highly variable. The higher flow in the MBBF group may be attributed to the arteriovenous shunting of microspheres, whereas lower flow in the IBBF group may be secondary to physiologic changes during CPB. This technique, described to measure IBBF, can estimate large variations in the natural right to left shunt that contributes to imbalance in the TAH.

Animals↗