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Biomedical subjects

C Weissman

Publications and source records attributed to C Weissman.

At least 19 recordsLinked to original sources

Mice homozygous for a modified beta-amyloid precursor protein (beta APP) gene show impaired behavior and high incidence of agenesis of the corpus callosum.

The amyloid precursor protein (beta APP) gene of the mouse was disrupted by homologous recombination; however, contrary to expectation, brain and other tissues still contained beta APP-specific RNA, albeit at a level 5-10 fold lower than wild-type and lacking the disrupted exon, which had been spliced out. The brain contained shortened beta APP-specific protein at a low level. Mutant mice were severely impaired in spatial learning and exploratory behavior and showed increased incidence of agenesis of the corpus callosum.

Agenesis of Corpus Callosum

Modulating effects of propofol on metabolic and cardiopulmonary responses to stressful intensive care unit procedures.

OBJECTIVE: Patients in the intensive care unit (ICU) undergo acute increases in metabolic and cardiopulmonary demands in response to routine care interventions, such as chest physical therapy. This study examined whether the short-acting drug, propofol, could blunt the responses to chest physical therapy. DESIGN: Prospective, randomized, crossover (placebo vs. drug) study. SETTING: University hospital surgical ICU. PATIENTS: Postoperative ICU patients being ventilated in the synchronized intermittent mandatory ventilation mode. INTERVENTIONS: Two groups of 16 patients were studied. Each patient received two successive sessions of chest physical therapy. In random fashion, one was preceded by the administration of placebo and the other by an intravenous bolus of propofol (0.75 mg/kg in one group and 0.35 mg/kg in the other group). Each session was preceded and followed by a period of rest. MEASUREMENTS AND MAIN RESULTS: The increases in oxygen uptake, CO2 elimination, oxygen delivery, heart rate, and systolic blood pressure associated with chest physical therapy were attenuated with the low dose and suppressed with the high dose of propofol. The Paco2 concentration was slightly increased during both placebo and drug administration. CONCLUSIONS: Propofol, in the doses administered in this study, significantly reduced the hemodynamic and metabolic stresses caused by chest physical therapy.

Adult

Do synthetic adrenergic agents interfere with the measurement of endogenous plasma catecholamine concentrations?

PURPOSE: It is common to administer synthetic sympathomimetic and sympatholytic agents in the intensive care unit and operating room. The present study examines whether such agents, as well as the products of catecholamine metabolism, interfere with the quantitation of endogenous catecholamines by high-performance liquid chromatography. METHODS: Samples of drugs and metabolites were assayed before and after alumina extraction and their relative retention times were compared with dopamine, norepinephrine, and epinephrine relative retention times. Blood samples from patients receiving these drugs were also assayed for their interferences with catecholamine determination. RESULTS: Phenylephrine interfered with the quantitation of epinephrine. Isoproterenol's peak was so delayed it appeared in the following chromatogram. Dobutamine had two small peaks in vitro, whereas in the patient samples only one peak was identified; the other was probably masked by the dopamine peak. Labetalol had one peak when the pure drug was assayed but multiple peaks in patient samples, that were probably caused by metabolites of labetalol. CONCLUSION: Synthetic adrenergic agents and catecholamine metabolites can potentially interfere with the quantitation of the endogenous catecholamines. Thus, it is important to examine whether such interference occurs when conducting high-performance liquid chromatography assays.

Adrenergic Agents

Pressure support ventilation attenuates the cardiopulmonary response to an acute increase in oxygen demand.

Critically ill patients undergo interventions, such as chest physical therapy, that acutely increase metabolic rate. Previous observations revealed that chest physical therapy is accompanied by increases of 40 to 50% in oxygen consumption (Vo2) and 40% in minute ventilation contributes to the rise in Vo2 and its associated hemodynamic responses. This was done by increasing mandatory ventilatory support during the chest physical therapy session: In phase 1 the mandatory ventilation rate was increased by 35% and in phase 2 pressure support ventilation 15 cm h2O was added. In phase 1 (n = 12), the increase in mandatory rate did not attenuate the chest physical therapy induced rises in heart rate, arterial blood pressure and Vo2. The increase in minute ventilation when the mandatory rate was increased prevented a rise in PaCO2. In phase 2 (n = 15), no change in the increase in Vo2 with chest physical therapy was observed with the addition of pressure support. Yet the rises in heart rate and systemic and pulmonary artery pressures were attenuated, as was the increase in PaCO2. Respiratory rate did not increase as much with pressure support. There appears to be a role for pressure support ventilation in attenuating the pulmonary and hemodynamic responses to interventions that increase oxygen demand.

Adult

Metabolic measurements in the critically ill.

Measurements of VO2 and VCO2 can be used to calculate REE, which can be used to determine the caloric requirements and metabolic state of critically ill patients. These measurements are made using the gas exchange method--measuring the minute ventilation and the differences between the inspired and expired concentrations of oxygen and carbon dioxide. Mechanical ventilation provides a challenging environment in which to make these measurements because of elevated oxygen concentrations, fluctuating airway pressures, and humidity. Careful attention must be paid to details to ensure accurate measurements under these conditions.

Calorimetry, Indirect

Replication step.

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Biological Evolution

Encoding a post-operative coronary artery bypass surgery care plan in the Arden Syntax.

The Arden Syntax for medical logic modules (Arden) was used to test the feasibility of encoding large, complex care plans. The critical portions of an existing paper-based care plan for the management of patients following coronary artery bypass graft (CABG) surgery were encoded in Arden and an X-windows user-interface was developed. The Arden Syntax proved adequate for encoding all of the necessary functions of the care plan. The limitations of the current Arden Syntax and possible additions to Arden are discussed.

Artificial Intelligence

Midazolam attenuates the metabolic and cardiopulmonary responses to an acute increase in oxygen demand.

Critically ill patients are subjected to routine clinical activities that increase oxygen demand. This results in increased heart rate, blood pressure, minute ventilation, and oxygen delivery in patients with often already compromised cardiopulmonary systems. This study examines whether the benzodiazepine, midazolam, could attenuate the increase in metabolism, respiration, and circulation seen during chest physical therapy. Two groups of mechanically ventilated postoperative patients were studied. One group (n = 15) received, in random order, 0.015 mg/kg of midazolam and placebo prior to two consecutive chest physical therapy sessions, while the other (n = 13) received 0.030 mg/kg and placebo. Both doses of midazolam significantly attenuated the increases in oxygen consumption, heart rate, and systemic blood pressure observed during placebo administration. The cardiac output increase was also attenuated. Although midazolam reduced minute ventilation and respiratory rate, no excess CO2 retention occurred when the drug was administered likely as the result of reduced CO2 production. The administration of midazolam (0.015 mg/kg and 0.030 mg/kg) prior to chest physical therapy reduces metabolic, hemodynamic, and ventilatory responses to chest physical therapy.

Adult

Response of critically ill patients to increased oxygen demand: hemodynamic subsets.

OBJECTIVE: To ascertain how patients with different abnormalities of oxygen transport at rest respond to an acute increase in oxygen demand. DESIGN: Observational study with retrospective assignment to subgroups, based on resting oxygen extraction ratio or increased cardiac output. SETTING: University hospital surgical intensive care unit (n = 96). PATIENTS: Postoperative, mechanically ventilated, critically ill patients (n = 96). INTERVENTION: Chest physical therapy. MEASUREMENTS AND MAIN RESULTS: Metabolic, hemodynamic, and respiratory measurements were made during an initial rest period and then during chest physical therapy. During chest physical therapy, patients (n = 10) having low resting oxygen extraction ratios (< or = 0.20) increased oxygen extraction, without changing oxygen delivery (DO2); while those patients (n = 19) with high resting oxygen extraction ratios (> or = 0.30) increased DO2, but not oxygen extraction. Patients (n = 46) with oxygen extraction ratios between 0.2 and 0.3 had an intermediate response; both DO2 and oxygen extraction increased. The group (n = 19) with increased resting cardiac output (> 9 L/min) and associated low resting oxygen extraction ratios and high DO2 values, increased their extraction of oxygen during chest physical therapy. CONCLUSIONS: The response to an acute increase in oxygen demand was influenced by resting conditions and was characterized by the use of "reserve" capacity. Patients with a resting hyperdynamic state (high DO2 and low oxygen extraction) were able to further increase oxygen extraction during the increase in oxygen demand.

Adolescent

An in vitro evaluation of an instrument designed to measure oxygen consumption and carbon dioxide production during mechanical ventilation.

OBJECTIVE: To determine the ability of the Puritan-Bennett 7250 metabolic monitor to measure CO2 production and oxygen consumption (VO2) under simulated clinical conditions. DESIGN: An in vitro validation study. SETTING: Laboratory of a large university medical center. METHODS: An in vitro evaluation was performed by adding precise amounts of CO2 and nitrogen to a lung model to simulate CO2 production and VO2. CO2 production and VO2 values measured by the metabolic monitor were compared with simulated values at various FIO2 values (0.21 to 0.80), levels of positive end-expiratory pressure (0 to 20 cm H2O), and flow-by mode flow rates (0 to 20 L/min). This comparison was also made at increased peak airway pressures (60 cm H2O). The effects of various concentrations of oxygen on the accuracy of the CO2 production measurements were also examined. RESULTS: The measurements made by the instrument were within 7% of values predicted from the CO2 and nitrogen infusions. There was no effect of various oxygen concentrations on the accuracy of CO2 production measurements. CONCLUSION: Under the in vitro conditions tested, the metabolic monitor provided accurate measurements of VO2 and CO2 production.

Calorimetry, Indirect

Arterial pulse contour analysis trending of cardiac output: hemodynamic manipulations during cerebral arteriovenous malformation resection.

OBJECTIVE: Intravascular pressure and cardiac output monitoring are frequently performed in the operating room and intensive care unit. Currently, cardiac output is only measured intermittently, although continuous measurement would be preferable. One method proposed for measuring cardiac output continuously is arterial waveform pulse contour analysis. This study examines the utility of trending cardiac output using pulse contour analysis during manipulations of blood pressure. METHODS: Eleven patients were studied while undergoing resection of cerebral arteriovenous malformations. Cardiac output measured by pulse contour analysis was compared with thermodilution cardiac output measurements in patients subjected to induced hypotension with esmolol and restoration of blood pressure with phenylephrine. RESULTS: Esmolol infusion resulted in a decrease in mean arterial pressure from 81 +/- 13 to 62 +/- 7 mm Hg (p < 0.025), a decrease in thermodilution cardiac output from 6.4 +/- 0.9 to 4.4 +/- 1.1 L/min (p < 0.025), and a decrease in pulse contour cardiac output from 6.2 +/- 1.0 to 4.5 +/- 0.9 L/min. Phenylephrine increased mean arterial pressure from 68 +/- 6 to 95 +/- 9 mm Hg with no change in either thermodilution or pulse contour cardiac output. CONCLUSIONS: This study demonstrates that during surgery for arteriovenous malformations in the brain, the pulse contour method was able to reflect cardiac output accurately during induced hypotension with esmolol and during restoration of blood pressure with phenylephrine.

Adolescent

Stressing the critically ill patient: the cardiopulmonary and metabolic responses to an acute increase in oxygen consumption.

Critically ill patients frequently have compromised respiratory and hemodynamic function. Chest physical therapy has been previously shown to increase oxygen demand and therefore was used to examine how postoperative mechanically ventilated patients responded to an increased oxygen demand. We found that during chest physical therapy, oxygen consumption increased 52% +/- 37% (SD) over baseline values. There was a 35% +/- 32% increase in oxygen extraction and a 17% +/- 33% increase in oxygen delivery. Arterial and pulmonary artery pressures also increased. The cardiac output increase was due to increased heart rate with no change in stroke volume. The increases in minute ventilation and alveolar ventilation were not sufficient to eliminate the greater quantity of carbon dioxide produced, resulting in a small increase in PaCO2. There was no significant change in systemic vascular resistance. The increase in oxygen demand caused by chest physical therapy triggered an integrated physiological response that resulted in increased respiratory and cardiac performance. This in some ways, such as the lack of increase in systemic vascular resistance, resembles the response to exercise.

Adult

Physiologic variables and fluid resuscitation in the postoperative intensive care unit patient.

OBJECTIVE: To examine how critical surgical illness and its management alter some of the biochemical, physiologic, and hematologic parameters commonly used to monitor postoperative, critically ill patients. DESIGN: Prospective survey of 150 patients over 3 months. SETTING: University hospital surgical intensive care unit. PATIENTS: A total of 150 consecutive adult patients admitted to the surgery-anesthesiology intensive care unit. MATERIALS AND METHODS: The effects of surgery on serum albumin and total protein concentrations, and lymphocyte counts were investigated. This investigation was done by comparing the values before surgery with those values after surgery and by also comparing what happened after different types of surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After surgery, decreases in serum albumin concentrations were significantly related to the estimated blood loss and acute gain in body weight from intravenous fluid resuscitation. The decreases in serum albumin and total protein concentrations were greater after elective abdominal surgery than after elective thoracic surgery. Total lymphocyte counts were significantly (< 1000 cells/mm3) reduced only in patients undergoing abdominal surgery. CONCLUSIONS: Serum albumin and total protein concentrations and total lymphocyte counts were significantly reduced by surgical injury, with significantly greater decreases seen after abdominal than thoracic surgery. These decreases were caused, in large part, by the volume of intravenous fluid used in resuscitation and blood loss. The changes in these variables are thus dependent on the type of surgical stress and the perioperative fluid therapy.

Abdomen

Alfentanil attenuates the cardiopulmonary response of critically ill patients to an acute increase in oxygen demand induced by chest physiotherapy.

Critically ill patients often are subjected to interventions that acutely increase oxygen demand and require increased output of the cardiac and respiratory systems. This study explored whether alfentanil could attenuate the response to chest physical therapy, a procedure that increases oxygen consumption by 40%-50%. Patients were examined during two consecutive therapy sessions. In random order, they received either a placebo or alfentanil (30 or 60 micrograms/kg) 2 min before treatment. In Group 1 (n = 11, 30 micrograms/kg alfentanil) only the arterial blood pressure increases induced by chest physical therapy were attenuated. In Group 2 (n = 12, 60 micrograms/kg) alfentanil attenuated the increases in heart rate, central venous pressure, and pulmonary artery systolic pressures as well as systemic blood pressure. Neither dose of alfentanil altered the increases in oxygen consumption, carbon dioxide elimination, oxygen delivery, or extraction ratio. Thus alfentanil attenuated the hemodynamic responses to chest physiotherapy in a dose-dependent fashion. This was likely due to its vagotonic actions. In contrast, alfentanil had no effect on the balance between oxygen demand and delivery during chest physiotherapy. There was thus a dissociation between the hemodynamic and metabolic responses.

Adult