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Biomedical subjects

A K Dawson

Publications and source records attributed to A K Dawson.

At least 19 recordsLinked to original sources
PubMed2000

Genetic evaluation of pervasive developmental disorders: the terminal 22q13 deletion syndrome may represent a recognizable phenotype.

The evaluation of mental retardation is always a challenge to clinicians. The recognition of specific physical or behavioral characteristics can vastly improve diagnostic yield. Several genetic disorders have been identified to have certain behavioral characteristics, such as Williams syndrome, Smith-Magenis syndrome, and the velocardiofacial syndrome (VCFS). The deletion affecting the chromosome 22q in the most distal band (22q13) appears to define yet another neurobehavioral phenotype. In addition to our report, there are about 17 other cases published of this particular deletion syndrome. We describe three children who share features of developmental delay and pervasive behaviors in addition to normal to advanced growth patterns. Results of cytogenetic analysis suggest that the 3 patients share a deletion affecting the terminal 22q13 region. Two were found to have a cryptic deletion, in the third it was detected by conventional cytogenetics. The cryptic deletions were demonstrated using fluorescent in situ hybridization (FISH), where the control probe for the DiGeorge/VCFS region was deleted. While there remain gaps in our understanding of this particular deletion syndrome, we propose that patients with normal or advanced growth, significantly delayed speech, deviant development and pervasive behaviors, with minor facial dysmorphism, be screened for this deletion.

Autistic Disorder↗
PubMed1996

DNA initiates polymorphic structural transitions in lecithin.

The inverted micellar phase, obtained by treating lecithin and Ca(2+)-DNA complex with chloroform, was used as an intermediate step in the preparation of DNA-Ca(2+)-lecithin complex. DSC analysis demonstrated the involvement of a large fraction of lipid in the interaction with DNA. Freeze-fracture electron microscopy revealed (i) rod-like structures on the hydrophobic fracture surface of membranes and (ii) regular bundles of fibrils with a repeat distance of about 6 nm, which were located free in solution. Similar regular bundles of fibrils were also revealed by staining the samples with uranyl acetate. According to the suggested model, the observed structures are hexagonally packed inverted lipid tubes, with DNA located in their central cores. The possible biological relevance of the capability of Ca(2+)-DNA to initiate polymorphic phase transitions of lecithin is discussed.

Animals↗
PubMed1992

Ventricular fibrillation detection using the evoked electrogram from the braided endocardial defibrillation lead.

Life-threatening consequences can be the result of inappropriate classification of ventricular fibrillation for patients with implantable cardioverter defibrillators. The objective of this study was to determine if analysis of the asynchronously paced evoked electrogram using the braided endocardial defibrillation lead could improve the detection of ventricular fibrillation. The depolarization portion of the evoked electrogram was integrated to obtain the paced depolarization integral. The results demonstrated that the mean of the paced depolarization integral, its SD, and the mean +/- SD were significantly different between sinus rhythm and ventricular fibrillation (p < 0.005, p < 0.05, p < 0.01, respectively). These results suggest that the paced depolarization integral obtained with the braided endocardial defibrillation lead could improve the specificity and sensitivity of ventricular fibrillation detection.

Animals↗
PubMed1992

Differentiation between monomorphic ventricular tachycardia and sinus tachycardia based on the right ventricular evoked potential.

The differentiation between ventricular tachycardia (VT) and sinus tachycardia (ST) is problematic in some patients with implantable defibrillators and/or antitachycardia pacemakers. The integral of the ventricular endocardial evoked response, or paced depolarization integral (PDI), has been demonstrated to undergo characteristic changes with a variety of stimuli including catecholamines, pacing rate, and exercise. We hypothesized that the PDI recorded from a unipolar transvenous right ventricular endocardial catheter would differentiate VT from ST. The PDI was calculated from a unipolar pacing stimulus, delivered via a cathode in the right ventricular apex, and the reference electrode, a quadripolar catheter positioned in the superior vena cava. PDIs were measured in 22 patients during VT and sinus rhythm. The PDI measured during sinus rhythm was 579 +/- 240 microV-sec and the PDI during VT was 894 +/- 411 microV-sec (P < 0.001). In a subset of seven patients, PDIs were measured during VT, sinus rhythm, and ST induced by catecholamine infusion or exercise. In this subset, the PDI during sinus rhythm was 645 +/- 295 microV-sec, during ST 588 +/- 308 microV-sec (9% decrease from sinus, P = 0.05), and during VT 863 +/- 342 microV-sec (33.9% increase, P = 0.01). These data indicate that the measurement of the PDI is potentially useful in differentiating VT from ST.

Algorithms↗
PubMed1992

The measurement of the paced depolarization integral using the braided endocardial lead.

Previous studies have shown that the paced depolarization integral (PDI) data recorded in unipolar configuration could potentially improve the specificity of tachyarrhythmia classification in an implantable cardioverter defibrillator (ICD). However, the defibrillation protection would be compromised if the ICD case were used as an indifferent electrode. Since transvenous defibrillation leads are being investigated to be used with ICDs, this study determined if reliable PDI data could be obtained using the braided endocardial defibrillation lead (BEDL). The results demonstrated that comparable PDI values and PDI changes with epinephrine induced sinus tachycardia were obtained with all three tested sensing configurations: conventional unipolar, tip electrode to right ventricular defibrillation electrode, and tip electrode to superior vena cava defibrillation electrode. Therefore, the BEDL can be used to measure PDI data, which possibly may improve tachyarrhythmia classification in an ICD, without compromising its defibrillation protection.

Animals↗
PubMed1989

Radiation therapy in recurrent pleomorphic adenoma of the parotid.

Twenty-nine patients were treated by excision and post-operative irradiation following recurrence of pleomorphic adenoma (mixed tumor) of the parotid. Eighteen of 20 (90%) patients with a first recurrence were controlled comparing favorably with series employing surgery only. Radiation therapy has a role to play as a surgical adjuvant in the management of these tumors, in particular when surgical difficulties are encountered and for second or subsequent recurrences.

Adenoma, Pleomorphic↗
PubMed1986

The role of external beam radiation therapy after prostatectomy for prostate cancer.

The role of radiation therapy as an adjuvant to prostatectomy is evaluated in 21 patients. Eleven were treated prior to clinical recurrence with 100% local control, no serious complications, and 86% long-term survival. Ten were treated after local recurrence with 80% local control, no serious complications, and 71% long-term survival. These data and the available literature indicate that the patient found to have capsular penetration, seminal vesicle involvement, or positive surgical margins at prostatectomy can be salvaged by postsurgical radiation therapy. When this is done after recovery from surgery, rather than waiting for clinical recurrence, a lower radiation dose can be used (6000 rad vs. 7000 rad), improved local control is obtained (94% vs. 79%), and fewer serious complications are observed.

Aged↗
PubMed1986

Effect of Fluosol-DA on infarct morphology and vulnerability to ventricular arrhythmia.

Although the blood substitute perfluorochemical Fluosol-DA has been shown to reduce experimental myocardial infarct size, the electrophysiologic properties of the surviving myocardium have not been assessed. Twenty-six dogs underwent closed-chest occlusion of the proximal left anterior descending coronary artery. Prior to infarction animals were randomly assigned to one of three treatment groups: groups receiving blood exchange with either Fluosol-DA (F = 9) or autologous heparinized blood (H = 8), given 30 minutes following occlusion over the next 30 minutes (these animals were ventilated with 100% oxygen for 6 hours), or a control group (C = 9) receiving no exchange transfusion and ventilated with room air. On the third postmyocardial infarction day the animals underwent programmed stimulation. The area at risk was defined by injecting different colored microvascular dyes into the three coronary beds, and the area of necrosis was defined by sectioning ventricular slices and staining with Mallory's trichrome stain. Infarct size was significantly reduced in the Fluosol-DA-treated group as compared to the heparin-treated and control groups when expressed as a percentage of the area at risk (F = 53.3 +/- 10, H = 67.2 +/- 12.8, C = 73.6 +/- 11.4: F vs H p less than 0.05; F vs C p less than 0.01). Ventricular tachycardia was inducible and sustained in 16 animals (3F, 6H, and 7C), and there was morphologic correlation with greater endocardial necrosis and smaller viable epicardial regions. In the 10 animals (6F, 2H, and 2C) without sustained ventricular tachycardia, there was greater epicardial viability and sparing of the endocardial regions with irregularity of the borders between viable and necrotic myocardium. We conclude that Fluosol-DA not only decreases infarct size but also modifies infarct morphology to reduce electrical instability.

Animals↗
PubMed1985

Effect of perfluorochemical (Fluosol-DA) on infarct morphology in dogs.

To assess the effect of Fluosol-DA treatment on infarct morphology, detailed histologic examination was performed in 17 dogs with permanent proximal left anterior descending coronary artery occlusion. Two of the three groups of dogs received an equal blood volume exchange (40 ml/kg i.v.) with either Fluosol-DA (F) or heparinized autologous blood (H) 30 min post occlusion while being ventilated with 100% oxygen. A third group received no therapy (C). Animals were sacrificed 3 days post occlusion and sections were obtained for light and electron microscopy. Histologic studies showed that infarct size was statistically smaller in dogs treated with F 54 +/- 7% versus heparin 64 +/- 10% treatment or no therapy 79 +/- 6%. Fluosol-DA animals demonstrated decreased inflammatory infiltrate, larger viable subepicardial zones and greater endocardial sparing in the area surrounding the central zone of necrosis. By electron microscopy, perfluorochemical particles were found within endothelial and inflammatory cells in subepicardial zones of infarction. In midmyocardial zones, Fluosol-DA particles were present in capillaries, extracellular spaces and necrotic myocytes. In the normal myocardium Fluosol-DA particles were rarely seen within endothelial cells and never within the interstitium or myocytes. Thus, Fluosol-DA reduces infarct size and alters infarct morphology in the 3 day post permanent coronary occlusion model.

Animals↗
PubMed1985

Long-term results of local excision and radiotherapy in pleomorphic adenoma of the parotid.

Three hundred and eleven patients with primary pleomorphic salivary adenoma of the parotid gland seen between 1950 and 1971 are reviewed. All were managed by a combination of surgery, usually local excision, and irradiation. The minimum follow-up is 10 years. Recurrence rates at 0-5 years and 5-10 years were 1 and 1.5%, respectively, and all recurrences in this period were histologically or clinically benign. This recurrence rate is similar to those reported after superficial parotidectomy. After 10 years, however, the recurrence rate rose, becoming maximal at 15-20 years (4%) and yielding a cumulative risk of recurrence of 8.0% at 20 years. The late recurrences were predominantly malignant tumors. One tumor was probably radiation-induced; the remainder were compatible with spontaneous malignant transformation of benign pleomorphic adenoma, although radiation may have increased the incidence. In the absence of a comparable purely surgical series, this cannot be determined. The recommendation is made that the management of these tumors should be primarily surgical with irradiation reserved for patients presenting surgical difficulties. In addition, prolonged follow-up is necessary since there is a significant incidence of late recurrence and such recurrence may be more likely to be malignant regardless of the primary form of management.

Adenoma, Pleomorphic↗
PubMed1985

The QRS complex during transient myocardial ischemia: studies in patients with variant angina pectoris and in a canine preparation.

We made continuous electrocardiographic recordings on magnetic tape during 15 episodes of ischemia in five patients with variant angina to determine the characteristics of the QRS changes. Orthogonal leads were used and the electrocardiograms were analyzed visually and by digital computer. Changes were quantified by subtracting baseline electrocardiograms from those obtained during ischemia. Large changes in the QRS occurred during ischemia but the waveform quickly returned to baseline when the episode subsided. In all patients there was prolongation of the QRS duration and an increase in QRS voltage during the terminal 40 msec of the waveform in the lead(s) showing the most marked ST displacement. The increase in the terminal QRS could be represented by a vector directed toward the ischemic zone. In a given patient the amplitude of ST displacement varied between episodes, presumably because of variation in the intensity of ischemia, but the QRS changes were directionally similar in each episode. In two patients there was also a smaller change involving the initial 40 msec of the QRS that could be represented by a vector directed away from the ischemic zone. To determine the possible mechanism for the electrocardiographic changes, ischemic episodes of 120 to 150 sec were produced in seven dogs and electrocardiographic recording and analysis techniques similar to those used in patients were employed. Myocardial conduction velocity was measured in three directions in the ischemic zone and was correlated with simultaneous electrocardiographic recordings from the body surface. The electrocardiographic changes in the dog preparation were virtually identical to those in the patients and strongly correlated with a fall in myocardial conduction velocity. We conclude that the QRS changes during variant angina result from the altered excitation pattern produced by conduction delay in the ischemic zone. The probable cause for the increase in terminal QRS voltage is delayed (and uncancelled) activation of the ischemic zone.

Angina Pectoris, Variant↗
PubMed1984

Differential effects of O-demethyl encainide on induced and spontaneous arrhythmias in the conscious dog.

Encainide is highly effective in suppressing most nonsustained ventricular arrhythmias, but there is evidence that the drug is less effective and may worsen some arrhythmias, particularly in patients with sustained ventricular tachycardia. In most patients it is likely that the major antiarrhythmic effects of encainide are mediated through a potent metabolite, O-demethyl encainide. The effects of infusions of saline solution or O-demethyl encainide on spontaneous ventricular ectopic activity and ventricular fibrillation (VF) threshold were compared in 25 dogs with a mottled myocardial infarct produced by transient coronary occlusion. Plasma levels of the metabolite above 100 ng/ml suppressed (greater than 92%) the spontaneous ventricular ectopic activity that occurred 48 hours after MI, whereas saline solution had no effect. In 15 dogs treated with O-demethyl encainide, the VF threshold decreased an average of 23%, from a baseline level of 23 +/- 8 mA to 18 +/- 9 mA (p less than 0.05). There was a concentration-dependent fall in VF threshold with plasma concentrations of O-demethyl encainide above 150 ng/ml. In 2 dogs with very high plasma concentrations of the metabolite (greater than 1,000 ng/ml), VF was induced by right ventricular pacing alone (S1S1 300 ms). No change in VF threshold was observed in the 8 dogs treated with saline solution, and in each of these dogs VF could be terminated by the countershock protocol. However, in 7 of the 17 dogs treated with O-demethyl encainide, VF could not be terminated by the countershock protocol.(ABSTRACT TRUNCATED AT 250 WORDS)

Anilides↗
PubMed1984

Electrophysiological effects of high-dose propranolol in dogs: evidence in vivo for effects not mediated by the beta adrenoceptor.

Closed-chest dogs anesthetized with morphine and chloralose were studied to determine if direct or nonspecific cardiac electro-physiological effects of propranolol occur at clinically relevant plasma concentrations and to differentiate the nonspecific effects from those due to beta adrenoceptor blockade. In 19 dogs, ventricular monophasic action potential durations (MAP), ventricular effective refractory periods (VERP) and His bundle electrograms (A-H and H-V intervals) were measured at base line and during sequential infusions of isoproterenol, dl-propranolol and dl-propranolol plus an isoproterenol infusion designed to overcome beta blockade. A mean plasma propranolol level of 979 +/- 344 ng/ml produced a significant (P less than .05) prolongation of A-H (95 +/- 20-115 +/- 13 msec), MAP (179 +/- 26-194 +/- 14 msec) and VERP (159 +/- 12-177 +/- 13 msec). Infusion of the beta agonist, isoproterenol, returned A-H and MAP to values not significantly different from base line, whereas VERP remained prolonged at 174 +/- 11 msec (P less than .05). No significant changes occurred in a control group of 14 dogs infused with saline. In eight additional dogs, infusions of d- and dl-propranolol, given on separate days, were used to produce equal beta blockade determined by individual isoproterenol sensitivity tests. A-H, H-V, MAP and ventricular strength-interval curves (VRP) and diastolic thresholds (DT) were measured and treatment vs. base-line changes (delta) with d- and dl-propranolol were compared.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1983

Electrophysiologic actions of high plasma concentrations of propranolol in human subjects.

The authors have previously shown that 40% of patients whose ventricular arrhythmias respond to propranolol require plasma concentrations in excess of those producing substantial beta-receptor blockade (greater than 150 ng/ml). However, the electrophysiologic actions of propranolol have only been examined in human beings after small intravenous doses achieving concentrations of less than 100 ng/ml. In this study, the electrophysiologic effects of a wider concentration range of propranolol was examined in nine patients. Using a series of loading and maintenance infusions, measurements were made at baseline, at low mean plasma propranolol concentrations (104 +/- 17 ng/ml) and at high concentrations (472 +/- 68 ng/ml). Significant (p less than 0.05) increases in AH interval and sinus cycle length were seen at low concentrations of propranolol, with no further prolongation at the high concentrations; these effects are typical of those produced by beta-blockade. However, progressive shortening of the endocardial monophasic action potential duration and QTc interval were seen over the entire concentration range tested (p less than 0.05). At high concentrations, there was significant (p less than 0.05) further shortening of both the QTc and monophasic action potential duration beyond that seen at low propranolol concentrations, along with a progressive increase in the ratio of the ventricular effective refractory period to monophasic action potential duration. No significant changes were seen in HV interval, QRS duration or ventricular effective refractory period. In summary, the concentration-response relations for atrioventricular conductivity and sinus node automaticity were flat above concentrations of 150 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1983

Electrophysiologic actions of O-demethyl encainide: an active metabolite.

Differences between the electrophysiologic actions of the antiarrhythmic agent encainide have been reported after short-term intravenous and oral administration. Only prolongation of the HV interval and QRS duration have been described immediately after short-term intravenous administration of encainide in dogs and man. However, during oral therapy or more prolonged infusions, prolongation of the AH interval and atrial and ventricular effective refractory periods have also occurred. In most patients receiving encainide therapy, metabolites (O-demethyl encainide and 3-methoxy-O-demethyl encainide) accumulate during prolonged therapy to concentrations greater than those of the parent drug. We compared the electrophysiologic action of O-demethyl encainide with that of saline in anesthetized dogs to determine if this metabolite has pharmacologic activity and whether its electrophysiologic effects could account for the disparities noted between effects of intravenous and oral encainide therapy. An initial pharmacokinetic evaluation allowed design of a series of loading and maintenance infusions that produced plasma concentrations similar to those seen during encainide therapy in man (concentration after first maintenance dose, 149 +/- 27 ng/ml [+/- SE] and after second maintenance dose, 230 +/- 45 ng/ml). Significant increases in atrial effective refractory period and ventricular refractoriness, and prolongation of AH interval and HV conduction time were observed. These effects are similar to those reported after prolonged oral encainide therapy but are substantially different from those seen after short-term infusions of encainide. These findings indicate that the difference between the electrophysiologic actions of intravenous and oral encainide may be due to pharmacologic effects of at least one encainide metabolite, O-demethyl encainide.

Action Potentials↗
PubMed1980

Effect of pentobarbital anesthesia on vulnerability to ventricular fibrillation.

Ventricular fibrillation threshold (VFT), frequently determined in dogs during pentobarbital sodium anesthesia, usually is replaced by a single repetitive extrasystole threshold (SRET) or a multiple repetitive extrasystole threshold (MRET) determination in conscious animals and in the human being. In the present study SRET, MRET, and VFT were determined initially in 39 pentobarbital sodium-anesthetized dogs. One week later these three thresholds were redetermined during anesthesia in 13 of the 39 dogs (control group). In the remaining 26 dogs (experimental group), thresholds were redetermined while the dogs were conscious. Significant changes in threshold values occurred only in the experimental group for VFT (P < 0.001) and MRET (P < 0.02). The square of the linear correlation coefficient showed conscious state MRET to be a good predictor of conscious state VFT (R2 = 0.90). Conscious state SRET and anesthetized state VFT showed less predictiveness for the conscious VFT (R2 = 0.72 and 0.51, respectively). These data indicate that MRET may be preferable to SRET as an index of VFT. The SRET, MRET, and VFT determined during pentobarbital anesthesia may not accurately reflect the value of these parameters in the conscious animal.

Animals↗