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Biomedical subjects

G Gorman

Publications and source records attributed to G Gorman.

At least 19 recordsLinked to original sources

Phase II trial of all-trans retinoic acid in metastatic non-small cell lung cancer.

The toxicity and marginal effectiveness of cytotoxic chemotherapy in metastatic non-small cell lung cancer (NSCLC) necessitates the search for new agents. Preliminary data in lung cancer and other malignant and premalignant disorders have identified retinoid compounds as potentially useful antitumor agents. Twenty-eight patients with metastatic NSCLC were treated with oral all-trans retinoic acid in a phase II trial. The study population consisted of patients with excellent performance status and minimal weight loss. Toxicities were generally mild and included cutaneous effects, headache, and myalgia. A significant number of patients developed elevations of hepatic transaminases or hyperlipidemia and 3 patients had treatment-related leukocytosis. Two patients (8%) achieved a partial response, and 1 had a mixed response. The duration of remission in the 2 responders was 7 and 13 months and the median survival of all patients 7 months. Therefore, all-trans retinoic acid has minimal activity as a single agent in NSCLC but warrants further study in combination with biological agents and chemotherapy.

Adult

First hints in non-small cell lung cancer (NSCLC).

All-trans retinoic acid was evaluated in metastatic measurable non-small cell lung cancer. All-trans retinoic acid was given at 175 mg/m2 orally on a daily basis. Twenty-eight patients (median age 58, 16 males, 12 women) had an ECOG performance status of 0 (26 patients) and 1 (two patients). Sixteen of the 28 had no weight loss. Eleven had between 5 and 10% and only one had greater than 10% weight loss at time of entry. Toxicities included cutaneous (cheletis 25/28), fatigue (10/28), myalgias/anthralgias (9/28), and headache (17/28). Alterations in triglycerides and hepatic transaminases were noted in a majority of patients. Two partial responses occurred in patients with adenocarcinoma. Both responses were 7 months in duration. Activity of all-trans retinoic acid in metastatic non-small cell lung cancer is minimal, but due to its low toxicity profile it should be tested in setting with other agents.

Adenocarcinoma

Transcatheter radiofrequency ablation in the canine right atrium.

The feasibility of using radiofrequency energy for potential ablation of atrial tachycardia foci was assessed by performing transcatheter ablation in the right atrium in 11 closed-chest dogs. Single-pulsed radiofrequency (750 kHz) energy was delivered to the right atrium (29-254 J) between the tip electrode of a standard 6 Fr quadripolar catheter and a chest patch electrode. There were no significant arrhythmias or complications noted. Dogs were sacrificed 0-29 days after ablation to assess acute and subacute effects of this technique. Of 47 attempted ablations, 36 well-delineated coagulative lesions were identified. The lesions had a mean dimension of 5.2 +/- 0.57 mm (+/- SE) in length, 3.9 +/- 0.27 mm in width, and 2.6 +/- 0.17 mm in depth. Transmural necrosis was noted in 6 of 36 lesions (17%) without perforation. A thin layer of mural thrombus was found in 5 of 36 lesions (14%). Thus, this technique appears to be feasible and relatively safe for right atrial ablations in a short-term follow-up period. The potential application of this method to ablate right atrial tachycardia foci needs to be further investigated.

Animals

Catheter ablation of the ventricular septum with radiofrequency energy.

The safety and feasibility of performing catheter ablation of the ventricular septum with radiofrequency energy was assessed in a closed-chest canine model. Radiofrequency energy (750 kHz) was delivered in a bipolar manner via the distal electrodes of two quadripolar catheters positioned across the ventricular septum in 10 dogs at two sites. Each site received from 159 to 823 joules of delivered energy over one to three applications. Four additional dogs underwent unipolar radiofrequency ablation with 331 to 767 joules of delivered energy to each septal site. No significant acute or latent arrhythmias were noted. Dogs were killed at 1 day, and at 1, 2, and 4 weeks after the procedure. Out of a possible 40 potential ablation sites on each side of the septum after bipolar ablation, 21 (53%) discrete endocardial lesions were identified, ranging in size from 4 x 3 x 1.5 to 10 x 8 x 4 mm. When 352 joules or more delivered energy was applied per site, lesions were located at 18 of 28 (64%) possible sites. After unipolar radiofrequency ablation, similarly sized lesions were identified at 15 of 16 (94%) ablation sites. Histologic examination demonstrated well-delineated round or ovoid-shaped lesions with microscopic thrombi overlying two lesions. In conclusion, catheter ablation of the ventricular septum with radiofrequency energy appears capable of safely producing discrete areas of necrosis and may provide an alternative to direct current (DC) energy for catheter ablation of ventricular tachycardia originating from the septum.

Animals

Effects of different pacing modes on left ventricular relaxation in closed-chest dogs.

Ventricular relaxation is an important determinant of ventricular filling; impaired relaxation may decrease cardiac output and stroke volume. Relaxation has been shown to occur more quickly following beats with an increased extent of systolic fiber shortening. Since cardiac output and stroke volume are greater during atrioventricular (AV) sequential pacing than during ventricular pacing at identical heart rates, we reasoned that AV sequential pacing would improve relaxation. To assess this hypothesis we studied 11 dogs with chronic (1-3 months) complete heart block (CHB) induced by radiofrequency catheter ablation of the His bundle. Right and left heart pressures, thermodilution cardiac output, and single plane ventriculography were recorded during baseline rhythm (CHB), and VVI, and AV sequential pacing at a heart rate greater than the sinus rate. None had ventriculoatrial conduction. During AV sequential pacing, the AV interval was set at 150 msec. Cardiac output and stroke volume were significantly increased in the AV sequential compared to the VVI pacing mode. Left ventricular pressures, maximal positive and negative dP/dt, and the time constant (T) of isovolumic pressure decay were not different in the two modes. We conclude that despite increased stroke volume in the AV sequential pacing mode, relaxation is unchanged. We believe the lack of change in relaxation is due to nonuniform ventricular activation when depolarization is initiated at the right ventricular apex.

Animals

Determinants of impedance rise during catheter ablation of bovine myocardium with radiofrequency energy.

Recently, radiofrequency (RF) energy has been used as an alternative energy source to direct-current (DC) electricity for catheter ablation of recurrent tachyarrhythmias. Since delivered energy is inversely related to impedance, factors that cause impedance rise during catheter ablation impede the ability to ablate tissue. To elucidate some of the factors responsible for impedance rise during RF (750 kHz) catheter ablation using a constant voltage RF generator, the effects of the following variables on impedance were studied in an in vitro bovine heart model: power setting (10-70 W), pulse duration (10-60 sec), catheter contact pressure (5-120 gm), repeated applications (2-4), and immersion media (saline vs citrated blood). Baseline impedance in blood was twice that of saline (190 vs 80 ohm) and rises in impedances occurred more rapidly in blood for the same energy settings. Increased power settings (greater than or equal to 30 W) and pulse duration (greater than or equal to 30 sec at 20 W) were associated with impedance rises in blood medium. Typically, impedance rises in blood were associated with blood coagulum on the catheter electrodes. Impedance rises in both saline and blood media were also associated with tissue charring and endocardial surface disruption. Once a rise in impedance occurred at the ablation site, repeated applications to the same site resulted in a more rapid rise in impedance. Catheter contact pressure of 80 gm or more also resulted in rapid impedance rise. These data suggest that factors other than set power and duration may also contribute to impedance rises during RF ablation. These findings may have important clinical implications in performing catheter ablation with RF energy.

Animals

Chronic incomplete atrioventricular block induced by radiofrequency catheter ablation.

To determine if catheter ablation of the atrioventricular (AV) junction with radiofrequency energy can induce chronic incomplete (first- and second-degree) AV block to avoid the need for a permanent pacemaker, 20 closed-chest dogs were studied. Group 1 (10 dogs) received radiofrequency energy (750 kHz) with a fixed power setting (5 or 10 W) while increasing the pulse duration from 10 to 50 seconds for each application. Group 2 (10 dogs) received energy with a fixed pulse duration (20 or 30 seconds) while increasing the power setting from 5 to 10 W or from 10 to 20 W during each energy delivery. Radiofrequency energy was delivered between a chest-patch electrode and the distal electrode of a regular 7F tripolar His bundle catheter. For each application, the energy delivery was interrupted when 1) the PR interval prolonged (greater than 50%) or 2) second-degree or complete AV block occurred and persisted up to 5 seconds. The ablation procedure ended when there was 1) persistent PR prolongation (greater than 50%) or persistent second-degree AV block (lasting greater than 30 minutes) after ablation, 2) occurrence of two consecutive transient (less than 1 minute) complete AV blocks after each energy delivery, or 3) complete AV block (lasting greater than 2 minutes) after ablation. Of seven dogs in group 1 and five dogs in group 2 in which incomplete AV block was achieved 1 hour after the procedure, six in group 1 and five in group 2 remained in incomplete AV block 2-3 months after ablation. One dog in group 1 progressed into complete AV block. Of the remaining three dogs in group 1 and five dogs in group 2 in which complete AV block was initially achieved 1 hour after ablation, two in group 1 and four in group 2 continued to have complete AV block, whereas one in each group had AV conduction returned to incomplete at 1-2 months of follow-up. Thus, a total of 13 dogs had chronic incomplete AV block induced by radiofrequency catheter ablation. Pathologic examination of the conduction system in two dogs with first-degree AV block, two dogs with second-degree AV block, and one dog with complete AV block showed discrete scars involving the approaches to the AV node and the AV node itself. It is concluded that, in most dogs studied, chronic incomplete AV block could be achieved by careful titration of the dosage of radiofrequency energy and by regulation of the ablation end points.

Animals

Short- and long-term effects of transcatheter ablation of the coronary sinus by radiofrequency energy.

Catheter ablation of left-sided atrioventricular accessory pathways through the coronary sinus by direct-current shock may be complicated by rupture and thrombosis of the coronary sinus and injury to the coronary arteries. This study examined short and long-term effects of radiofrequency catheter ablation of the coronary sinus in 20 closed-chest dogs to determine whether this technique is feasible for potential interruption of left-sided accessory pathways. Single-pulsed radiofrequency energy (750 kHz, 85-293 J) was delivered to three sites in the distal and middle coronary sinus between the distal (1) or the proximal electrodes (2 or 3) of a standard 6 French quadripolar catheter and a chest-wall patch electrode. Single-pulsed radiofrequency energy (78-293 J) was also applied to two sites near the ostium of the coronary sinus with the proximal (4) or the distal (1) electrode of the same catheter. Coronary artery and levophase coronary sinus angiograms obtained before and immediately after ablation, as well as before killing, showed intact vascular structures in all dogs. Right atrial, pulmonary arterial, and aortic pressures measured in three dogs did not change significantly at the time of energy delivery. No significant changes were found in atrioventricular nodal refractoriness and conduction. None of the dogs had significant rhythm disturbances during and after ablation as evaluated by ambulatory electrocardiographic monitoring and periodic rhythm strips at follow-up. Ten dogs were killed 1-7 days after ablation, three dogs were killed at 4 weeks, three dogs at 6 weeks, two dogs at 8 weeks, and two dogs at 12 weeks. Discrete lesions ranging in size from 3 x 3 to 8 x 10 mm2 in surface area and 0.5-4.5 mm in depth were found in the coronary sinus with most of the lesions extending to the left atrial and left ventricular myocardium. There was neither rupture of the coronary sinus nor occlusion of the coronary arteries. Mural thrombus was found in the coronary sinus on five acute lesions in two dogs, but none was noted on the chronic lesions, which was characterized by chronic granulation tissue and fibrosis. Two dogs in the study during chronic conditions had damage to branches of the underlying coronary artery that showed necrotizing arteritis and arterial sclerosis. Conduction system studies in four dogs showed some chronic inflammatory and fibrotic changes. Similar discrete lesions were found in situ in the coronary sinus of four postmortem human hearts with radiofrequency catheter ablation.(ABSTRACT TRUNCATED AT 400 WORDS)

Angiography

Antibody response to serogroup A and C meningococcal polysaccharide vaccines in infants born of mothers vaccinated during pregnancy.

During the large epidemic of serogroups A and C meningococcal disease in Brazil, we studied the immunologic response to meningococcal polysaccharide vaccine in infants born to women vaccinated during pregnancy. Radioimmunoassay serum levels against serogroups A and C polysaccharide were more than threefold higher in vaccinated than in unvaccinated women at delivery. Cord blood levels were also threefold or higher in infants whose mothers were vaccinated while pregnant compared to infants born of unvaccinated mothers. Within 3 mo, the infants' A and C serum antibody levels declined by approximately 80%. When vaccinated at about 6 mo of age, infants born of vaccinated mothers had antibody responses to A and C polysaccharide vaccines indistinguishable from those born of unvaccinated mothers. The response did not vary with the trimester of vaccination. We conclude that the vaccination of pregnant women with groups A and C meningococcal polysaccharide vaccine does not produce immune tolerance in the subsequently born infants.

Antibodies, Bacterial

Isolation of the Legionnaires' disease bacterium from environmental samples.

We analyzed 24 environmental samples collected in or near the Indiana Memorial Union, where an epidemic of Legionnaires' disease occurred in early 1978. We conducted fluorescent antibody analyses and culture on F-G and charcoal yeast extract agars of each sample directly; splenic tissue of guinea pigs inoculated with the sample; and yolk sacs from embryonated eggs inoculated with splenic tissue of guinea pigs injected with the sample. Legionnaires' disease (LD) bacterium was isolated from seven of the 24 samples: one water sample from the air-conditioner cooling tower of the Union; three water samples from a stream near the Union; and three mud samples from the same stream. The LD bacterium strains were of three different serotypes. These findings indicate that LD bacteria may be widespread in nature.

Air Conditioning

Hemophilus influenzae type b disease in a day-care center. Report of an outbreak.

Four episodes of serious Hemophilus influenzae type b infection occurred in three children attending a day-care center. This was 100 times the expected annual total. The pharyngeal carriage rate of Hib was 60% for siblings of patients, 20% for adult household contacts, and 5% for well children at the center. No carriers were found in control populations. Escherichia coli K100, which cross-reacts serologically with Hib, was found in rectal swabs of 20% of family contacts of patients and 3.5% of well children at the center. It was recovered from two of seven persons who carried Hib in the pharynx and two of 75 who did not (P = 0.035), suggesting that carriage of one organism may facilitate carriage of the other. In a randomized prospective trial with 85 patient contact, Hib carriage was eradicated in all of four carriers given ampicillin and in all of three given rifampin. There were no statistically significant differences in the rate of adverse reactions in the two treatment groups. No further cases were reported.

Ampicillin

Passover.

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Caregivers