Biomedical subjects

M E Alexander

Publications and source records attributed to M E Alexander.

11 recordsLinked to original sources

PubMed1992

A nuclear magnetic resonance investigation of the upper airways in ferrets. I. Effects of histamine and methacholine.

Alterations induced in the upper airways of ferrets by intranasal provocation with methacholine (MC) and histamine (HS) were monitored using proton magnetic resonance imaging (MRI) and spin-spin relaxation rate (R2) measurements. Both MC and HS cause a significant increase in the MRI signal intensity and a decrease in R2 in the nasal turbinates. A dose-dependent response is observed for 20 to 315 nmol of HS, with a maximum increase in intensity of ca. 50% occurring above 80 nmol. A single unilateral challenge with MC yields a 62 +/- 3% increase in intensity. Control animals (saline-treated) show little change in image intensity. MC and HS cause decreases in the proton R2 by -27.0 +/- 5.5% and -17.2 +/- 4.3%, respectively. These data are indicative of an accumulation of fluid in the nasal airways. MRI provides an effective means to monitor changes in the nasal airways which occur as a result of pharmacological treatment.

Administration, Intranasal↗

PubMed1992

A nuclear magnetic resonance investigation of the upper airways in ferrets. II. Contrast-enhanced imaging to distinguish vascular from other nasal fluids.

Proton magnetic resonance imaging (MRI), used in conjunction with the intravascular contrast agent albumin-(Gd-DTPA), provides a means to distinguish vascular fluids from other nasal fluids in the upper airways. Ferrets were given an intravenous dose of albumin-(Gd-DTPA) followed by an intranasal challenge with either histamine (HS) or methacholine (MC). An observed increase in image intensity indicates that HS and MC both cause an accumulation of fluids in the nasal turbinate region. The MRI data are also influenced by the presence of blood, which contains the contrast agent, and a clear distinction can be made between vascular fluids and other nasal fluids (i.e., cellular and glandular secretions). The results show that HS causes an increase in vascular fluids in the nasal turbinates while MC does not. This methodology represents a new means to investigate airway pharmacology and the pathophysiology associated with various pharmacological agents, allergens, or viral infections.

Administration, Intranasal↗

PubMed1992

Sedation of children for technical procedures: current standard of practice.

We sought to define the current standard of care for children undergoing sedation for painless diagnostic procedures by sending questionnaires to 284 pediatric residency program directors in North America. From the 89 responses, we determined that departments of pediatrics set sedation policies for children in most institutions, often with formal written guidelines for these procedures. Most require that children have some form of cardiorespiratory monitoring while under sedation and that they are attended by individuals trained in cardiorespiratory resuscitation until the child is fully recovered. The use of parents to transport and monitor the sedated child is uncommon, and total lack of monitoring is rare. Chloral hydrate in dosages of 25 mg/kg to 100 mg/kg is the most common drug used for sedation; DPT, a combination of parenteral Demerol (meperidine), Phenergan (promethazine), and Thorazine (chlorpromazine), at a maximum dose of 2 mg/1 mg/1 mg/kg is the second; and pentobarbital in a dosage of 5 mg/kg to 7 mg/kg is the third. These sedation regimens were associated with few serious side effects, except that two deaths were reported in infants with congenital heart disease who were sedated with DPT. We believe this survey may reflect the current standard of practice for sedation in North American infants and children undergoing diagnostic procedures.

Attitude of Health Personnel↗

PubMed1992

Venous hyperoxia after cardiac arrest. Characterization of a defect in systemic oxygen utilization.

BACKGROUND: Supranormal mixed venous oxygen saturation (mixed venous hyperoxia), although reported, has never been characterized in humans resuscitated from cardiac arrest (postarrest cardiogenic shock). By contrast, cardiogenic shock without cardiopulmonary arrest (primary cardiogenic shock) is accompanied by mixed venous hypoxia under similar conditions of low oxygen delivery (DO2). The appearance of mixed venous hyperoxia indicates an excessive supply relative to demand in perfused tissue or cellular impairment of oxygen utilization, ie, low systemic oxygen consumption (VO2). Failure to improve VO2 has been associated with a poor outcome in other shock states. STUDY OBJECTIVE: This study evaluates the clinical significance of mixed venous hyperoxia and its implications for impaired systemic oxygen utilization. The oxygen transport patterns in surviving and nonsurviving cardiac arrest patients are compared for their prognostic and therapeutic implications. STUDY DESIGN: Consecutive, nonrandomized series. SETTING: Large urban emergency department (ED). PARTICIPANTS: Adult normothermic, nontraumatic out-of-hospital cardiac arrest patients presenting to the ED who develop a return of spontaneous circulation (ROSC). INTERVENTIONS: On arrival to the ED, a fiberoptic catheter was placed in the central venous position for continuous central venous oxygen saturation monitoring (ScvO2). A proximal aortic catheter was placed via the femoral artery for blood pressure monitoring. Upon ROSC, the fiberoptic catheter was advanced to the pulmonary artery. Mean arterial pressure (MAP), cardiac index (CI), VO2, DO2, systemic oxygen extraction ratio (OER), and systemic vascular resistance index (SVRI-dynes.s/cm5.m2) were measured immediately and every 30 min. The duration of cardiac arrest (DCA) in minutes and amount of epinephrine (milligrams) administered during ACLS was recorded. MEASUREMENTS AND RESULTS: Twenty-three patients were entered into the study. Survivors (living more than 24 h) and nonsurvivors (living less than 24 h) were compared. CONCLUSIONS: These findings indicate an impairment of systemic oxygen utilization in postarrest cardiogenic shock patients. In spite of a lower DO2 than survivors, the OER in nonsurvivors remained lower than expected. Venous hyperoxia is a clinical manifestation of this derangement. Epinephrine dose may have a causal relationship. The inability to attain a VO2 of greater than 90 ml/min.m2 after the first 6 h of aggressive therapy was associated with a 100 percent mortality in 24 h.

Aged↗

PubMed1991

Two dynamic modes of striatal function under dopaminergic-cholinergic control: simulation and analysis of a model.

A neural network model based on the anatomy and physiology of the matrix compartment of the striatum is described. The model consists of a network of neurons which are mutually inhibitory within a defined domain. A membrane potassium conductance (GK) under dopaminergic-cholinergic control is included in the model. Computer simulation results show that changes in GmaxK can modulate the behaviour of the network to produce either competition or coactivation among striatal output neurons. An analysis of a two-neuron system based on the model shows that the maximum steepness of the threshold function plays a decisive role in the dynamics, in particular with regard to the competition that exists between the neurons. Competitive interactions predominate at low GmaxK, while coactivation predominates at high GmaxK. We suggest that the former dynamic governs reciprocal inhibition of antagonistic muscles, while the latter governs cocontraction and rigidity. The model offers insights into the control of striatal neurodynamics by GmaxK which establish closer links between dopaminergic actions in the striatum and the mechanism of Parkinsonian rigidity. A prediction of the model is that acetylcholine should increase GKmax in striatal output neurons.

Acetylcholine↗

PubMed1977

Modification of tyrosine residues of the lactose repressor protein.

Reaction of the lactose repressor protein from Escherichia coli with high molar excesses (up to 800 fold) of tetranitromethane resulted in modification of tyrosine residues in the amino-terminal and core regions of the molecule. Tyrosines 7 and 17 exhibit significant reactivity at low levels (5-10 fold molar excess) of tetranitromethane. The loss of operator binding activity upon nitration at these low concentrations of reagent indicates involvement of these two tyrosines in the binding process. Inducer binding activity was maintained at approx. 90% of unreacted repressor for all excesses of reagent studied. Addition of inducer to the repressor prior to reaction resulted in decreased modification of tyrosines in the core region, but anti-inducers did not affect the reaction significantly. The effect of inducers on the pattern of reaction apparently reflects the conformational change which occurs upon binding of these ligands. Acetylation of the repressor protein with N-acetylimidazole modified lysines and tyrosines with complete loss of operator binding activity and retention of 75-80% of inducer binding activity.

Bacterial Proteins↗

PubMed1974