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Biomedical subjects

S L Schwartz

Publications and source records attributed to S L Schwartz.

At least 19 recordsLinked to original sources
PubMed1992

A physiologically based pharmacokinetic model for nicotine and cotinine in man.

Physiologically based pharmacokinetic (PBPK) models have been developed describing the disposition kinetics of nicotine and its major metabolite, cotinine, in man. Separate 9-compartment, flow-limited PBPK models were initially created for nicotine and cotinine. The physiological basis for compartment designation and parameter selection has been provided; chemical-specific tissue-to-blood partition coefficients and elimination rates were derived from published human and animal data. The individual models were tested through simulations of published studies of nicotine and cotinine infusions in man using similar dosing protocols to those reported. Each model adequately predicted the time course of nicotine or cotinine concentrations in the blood and urine following the administration of nicotine or cotinine. These individual models were then linked through the liver compartments to form a nicotine-cotinine model capable of predicting the metabolic production and disposition of cotinine from administered nicotine. The potential for integrating this functional PBPK model with an appropriate pharmacodynamic model for the characterization of nicotine's physiological effects is discussed.

Cotinine↗
PubMed1992

Intracardiac echocardiography during simulated aortic and mitral balloon valvuloplasty: in vivo experimental studies.

The feasibility of intracardiac echocardiography with a low-frequency transducer to assess catheter position and detect complications during experimental aortic and mitral balloon valvuloplasty was studied in 10 dogs. Intracardiac echocardiography was performed with a transesophageal echocardiographic probe placed in the right atrium. In all instances high-quality images of cardiac structures were obtained. The guide wire and balloon catheter were clearly seen as they crossed the valves. With inflation the balloon was seen as a hyperechoic structure. Doppler echocardiography documented aortic regurgitation after inflations. Acute pericardial effusion was instantly detected. It is concluded that intracardiac echocardiography is a potentially useful technique for cardiac imaging, assessing wire and balloon catheter position, evaluating valvular regurgitation, and instantly detecting acute pericardial effusion. Further research in humans with low-frequency, catheter-based transducers needs to be performed.

Animals↗
PubMed1992

Ureteroscopic treatment of urothelial carcinoma of the ureter and renal pelvis.

From June 1987 to September 1990, 12 patients were evaluated for ureteroscopic treatment of upper urinary tract neoplasms. Four patients were not considered candidates because of technical reasons. Each of these patients was treated by nephroureterectomy. A total of 8 patients underwent ureteroscopic therapy with a neodymium:YAG laser 1 to 11 times (median 2) for the treatment of 3 proximal ureteral or pelvic lesions and 7 distal ureteral lesions. One patient had local progression and 1 failed subsequent laser treatment for technical reasons. Both of these individuals were salvaged with an operation. Three patients were without recurrence for 15, 21 and 36 months. Two patients had multiple superficial local recurrences and continue to be managed endoscopically without local progression for 12 and 32 months. One patient was asymptomatic 16 months after treatment but he has refused followup evaluation. Of 7 patients with ureteral tumors who were believed to be candidates for endoscopic therapy 5 have had the tumors controlled by this method of treatment. Only 1 renal pelvic tumor has been successfully treated. Most patients with tumors in the renal pelvis are not candidates for rigid endoscopic therapy because of the tumor size and location. In selected individuals ureteroscopic laser treatment of upper urinary tract transitional cell carcinoma can achieve local control with renal preservation.

Aged↗
PubMed1992

Cognitive dysfunction in a patient with long-term occupational exposure to ethylene oxide. Role of ethylene oxide as a causal factor.

This case illustrates a comprehensive approach to assessing causality in a woman with apparent cognitive dysfunction, as measured by neuropsychological testing, and a 10-year history of occupational exposure to ethylene oxide. The analysis included a multidisciplinary examination of the patient, which took place several years after the termination of her exposure. In addition, all of the patient's prior medical and psychiatric records were reviewed, as were the records of her employer to ascertain her exposure history. Our evaluation revealed a pattern of neuropsychological findings not consistent with nervous system damage secondary to an organic effect of ethylene oxide. A more likely causal hypothesis is adopted: the patient's apparent cognitive dysfunction had a psychiatric etiology. This case also illustrates the potential impact of a patient's involvement in legal proceedings related to claims of neurocognitive dysfunction.

Adult↗
PubMed1991

Intracardiac echocardiography: current developments.

Intracardiac echocardiography refers to the method of imaging cardiac structures from intracardiac locations with the use of ultrasound catheters. Advances in catheter-based interventional cardiologic procedures to treat cardiovascular lesions and the problems encountered during those procedures due to inadequate guidance provided by fluoroscopy have given the impetus to develop other guidance modalities. Experimental explorations with intracardiac ultrasound probes have indicated that detailed visualization of cardiac structures in real-time is possible by intracardiac ultrasound. Recent advances in catheter-based ultrasound technology make it feasible to safely pass small-sized catheters in humans into various intracardiac locations and acquire images of valvular structures and various chambers. Experience with 20 MHz ultrasound catheters indicates that high resolution images of normal and abnormal structures can be obtained if the catheter is manipulated close to the region of interest. The problem of the limited depth of field associated with 20 MHz catheters has led to the fabrication of catheters with lower frequency ultrasound elements. Experimental and clinical experience with 12.5 MHz ultrasound catheters points to the capability and potential of intracardiac echocardiography to not only display normal structures but also aid in the identification of valvular abnormalities, chamber dysfunction and pericardial effusions. In addition, aortic disorders such as acute dissection, coarctation and atherosclerotic disease could be delineated. Similarly, abnormalities involving the pulmonary arteries such as pulmonary embolism, organized thrombi, peripheral pulmonary arterial stenoses, and pulmonary hypertension-induced vascular changes could be recognized. Many modifications in the catheter design are being explored. With further work in the area of catheter technology and ultrasound image processing, intracardiac echocardiography is likely to become a clinical tool.

Animals↗
PubMed1991

Left ventricular diastolic collapse. An echocardiographic sign of regional cardiac tamponade.

BACKGROUND: Cardiac tamponade after cardiac surgical procedures is often associated with hemodynamically significant localized pericardial effusions. The localized collection of pericardial effusion in the postoperative period and the atypical presentation of cardiac tamponade limit the use of conventional clinical and echocardiographic signs usually seen with a circumferential pericardial effusion. Observation of left ventricular diastolic collapse in the echocardiogram of a patient with postoperative regional cardiac tamponade prompted us to explore the frequency of this sign in regional cardiac tamponade. METHODS AND RESULTS: We retrospectively analyzed the echocardiograms of 18 patients with postoperative cardiac tamponade for the following echocardiographic findings: right atrial collapse, right ventricular diastolic collapse, left atrial collapse, and left ventricular diastolic collapse. Three of the 18 patients had circumferential pericardial effusion, and 15 had loculated pericardial effusion; in 10, the effusion was predominantly posterior, and in the other five, it extended laterally or inferiorly. The conventional echocardiographic signs of cardiac tamponade such as right atrial collapse, right ventricular diastolic collapse, and left atrial collapse were present in only 3, 1, and 3 of these 15 patients, respectively, but all exhibited left ventricular diastolic collapse. Increasing pressure within the compartment of a loculated pericardial effusion reaching the limit of pericardial distensibility and consequent transient reversal of transmural left ventricular pressure during diastole are most likely the basis for diastolic collapse of the thick-walled ventricle in a setting of regional cardiac tamponade. CONCLUSIONS: We conclude that left ventricular diastolic collapse is a frequent sign of regional cardiac tamponade and could be a useful marker of tamponade in postoperative patients.

Adult↗
PubMed1990

Clinical pharmacokinetics of moricizine.

Moricizine is well absorbed after oral administration and undergoes extensive first-pass metabolism. The drug has a large apparent volume of distribution (approximately 4 liters/kg), exhibits extensive plasma protein binding (approximately 95%) and produces at least 30 metabolites. Indirect evidence indicates that some of those metabolites may be pharmacologically active. The elimination half-life of moricizine is 2 to 6 hours, but its duration of antiarrhythmic action is much longer suggesting active metabolites. Moricizine induces its own metabolism with no change in pharmacologic effect. It also induces the metabolism of theophylline and specific pathways of antipyrine. Cimetidine reduces metabolism of moricizine but does not alter its pharmacologic effects. This observation provides further support for the hypothesis that the metabolites of moricizine contribute to the pharmacologic actions during therapy and indicate that plasma level monitoring is not likely to be of value. There are no known clinically significant pharmacokinetic interactions between moricizine and digoxin, warfarin or propranolol. Excessive prolongation of the PR interval has been seen in some patients receiving both digoxin and moricizine, probably due to additive electrophysiologic effects of the 2 drugs.

Anti-Arrhythmia Agents↗
PubMed1990

Effects of oral erythrosine (2',4',5',7'-tetraiodofluorescein) on the pituitary-thyroid axis in rats.

Erythrosine (FD&C Red Dye No.3) is a tetraiodinated derivative of fluorescein. Rats fed a 4% erythrosine diet for 30 months beginning in utero have an increased incidence of thyroid adenomas and adenocarcinomas. These tumors may be secondary to increased stimulation of the thyroid gland by TSH. This study was undertaken to determine if dietary erythrosine disrupts the pituitary-thyroid axis thereby altering serum thyroid hormone levels. TSH levels, or the pituitary's response to TRH. Rats were fed diets containing erythrosine (0.5, 1.0, 4.0%), sodium iodide (0.16%), or fluorescein (1.6%) for 3 weeks after which TRH testing was performed in vivo. Erythrosine produced a dose-dependent increase in serum T4 levels. With the 4% erythrosine diet, serum T4 and T3 levels and the free-T4 index were significantly increased, whereas the free-T3 index were significantly increased, whereas the free-T3 index was unchanged. Rats fed the 4.0% erythrosine diet had an exaggerated TSH response to TRH; 10 min after the TRH injection, serum TSH levels were 80% greater than TSH levels of control rats. Short-term administration of erythrosine to rats decreased hepatic T3 production by decreasing its conversion of T4 to T3, indicating that erythrosine decreases hepatic 5'-deiodinase activity. These data demonstrate that dietary ingestion of 4% erythrosine disrupts the pituitary-thyroid axis as evidenced by an increased TSH response to TRH. This effect is mediated by erythrosine or an iodinated metabolite, since ingestion of its fluorescein nucleus had no effect. Erythrosine's effects were not likely mediated by iodide, because serum T4 and T3 levels were elevated and iodide administration did not increase the TSH response to TRH. These data suggest that erythrosine increases the pituitary's TSH response to TRH by altering thyrotroph cell conversion of T4 to T3. Chronic erythrosine ingestion may promote thyroid tumor formation in rats via chronic stimulation of the thyroid by TSH.

Administration, Oral↗
PubMed1990

Intracardiac, intravascular, two-dimensional, high-frequency ultrasound imaging of pulmonary artery and its branches in humans and animals.

Intravascular ultrasound imaging is a promising new method for assessing vascular morphology. We evaluated the capability of intravascular ultrasound to quantify pulmonary artery (PA) morphology in vitro and explored the feasibility of in vivo PA imaging in animals and humans. In the in vitro study of 15 PA segments, we used a 20-MHz prototype ultrasound catheter. Intravascular ultrasound (y) provided crisp images of PA segments and demonstrated excellent correlations with anatomic measurements (x) in the estimation of luminal area (y = 0.89x + 2.95, r = 0.99, p less than 0.001), luminal diameter (n = 30, y = 0.79x + 0.96, r = 0.92, p less than 0.001), and vessel wall thickness (n = 60, y = 0.65x + 0.33, r = 0.85, p less than 0.001). We subsequently introduced the probe into the PA of 10 dogs and were able to obtain real-time, two-dimensional images of the main PA, its major branches, and farther smaller branches as far as the wedge level. To evaluate the in vivo feasibility of PA imaging in conscious humans, we used a commercially available, 20-MHz intravascular ultrasound (IVUS) catheter in 22 subjects through a femoral or jugular venous sheath at the end of standard diagnostic cardiac catheterization. In 20 subjects, we acquired dynamic, high-resolution, cross-sectional images of the proximal and distal PA. Changes in shape and decreasing luminal area could be clearly recognized as the IVUS catheter reached branching points and as it passed more distally. There were no complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Effects of oral erythrosine (2',4',5',7'-tetraiodofluorescein) on thyroid function in normal men.

Erythrosine (Er), a tetraiodinated derivative of fluorescein, is a coloring agent widely used in foods, cosmetics, and pharmaceutical products. Because of its high iodine content and previous reports demonstrating an inhibitory effect of erythrosine on hepatic 5'-monodeiodination, we studied the effects of this compound on thyroid function and serum and urinary iodide concentrations in normal subjects. Thirty normal men, equally divided into three treatment groups, each received a 14-day course of oral Er in doses of 20, 60, or 200 mg/day. Serum thyroxine (T4), triiodothyronine (T3), reverse T3 (rT3), thyroid stimulating hormone (TSH), protein-bound iodide (PBI), and total iodide concentrations, serum T3-charcoal uptake, and 24-hour urinary iodide excretion were measured on Days 1, 8, and 15. Thyrotropin-releasing hormone (TRH) tests were performed on Days 1 and 15. There were no significant changes in serum T4, T3, rT3, and T3-charcoal uptake values at any dose. In men receiving 200 mg Er/day, the mean basal serum TSH concentration increased significantly from 1.7 +/- 0.1 (SE) on Day 1 to 2.2 +/- 0.1 microU/ml on Day 15 (p less than 0.05), and the mean peak TSH increment after TRH increased from 6.3 +/- 0.5 to 10.5 +/- 1.0 microU/ml (p less than 0.05). There were no significant changes in basal or peak TSH responses in the men receiving 20 or 60 mg Er/day. Significant dose-related increases in serum total iodide and PBI concentrations occurred during all three doses, and significant dose-related increases in urinary iodide excretion occurred during the 60 and 200 mg/day Er doses. These data suggest that the increase in TSH secretion induced by Er was related to the antithyroid effect of increased serum iodide concentrations, rather than a direct effect of Er on thyroid hormone secretion or peripheral metabolism.

Adult↗
PubMed1979

Carotid catastrophe.

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Carotid Artery Diseases↗
PubMed1977

Induction of membrane alterations by norepinephrine: studies with macrophages and phospholipids monolayers.

Norepinephrine (8 mM) produced a rapid and readily reversible rounding and vacuolation in mouse peritoneal macrophages. The rapid onset and offset of these changes suggested something other than classical pinocytosis as a mechanism. The morphological changes were inhibited by cytochalasin B but not by propranolol. Norepinephrine lowered the contact angle between a macrophage monolayer and a sessile drop of saline. This indication of increased membrane hydrophilicity is consistent with an increase in membrane surface pressure. Norepinephrine had no effect on neutral phospholipid (phosphatidylcholine) monolayers but expanded acidic phospholipid (phosphatidylserine) monolayers over a wide range of surface pressures (15-40 dynes/cm). Based on these observations, it is suggested that norepinephrine may produce the morphological changes by expanding the macrophage membrane to the point of membrane buckling and/or by a viscotropic stimulation of membrane enzymes which, in turn, activate microfilaments.

Animals↗
PubMed1977

Accumulation of norepinephrine by macrophages and relationships to known uptake processes.

Incubation of mouse peritoneal macrophages with l-[3H]norepinephrine resulted in an apparent multiphasic accumulation of the catecholamine by the cells. Low temperature did and iodoacetate did not inhibit uptake. Part of the accumulation followed saturation kinetics; cocaine, metanephrine and phenoxybenzamine did not inhibit the observed uptake. On this basis, it was concluded that the uptake process or combination of processes could not be classified solely as uptake1, uptake2 or simple diffusion However, similarities between norepinephrine accumulation by macrophages and that by other extraneuronal tissues do exist. This, along with previous morphological data, suggests that the macrophage uptake may typify a component of extraneuronal accumulation of norepinephrine and that this component may, in part, result from a nonspecific membrane perturbation by norepinephrine.

Animals↗
PubMed1976

Comparative production of interferon by explanted lymphoreticular tissue and alveolar macrophages from rabbits and humans.

Studies were undertaken to compare interferon production among a variety of lymphoreticular cells, with emphasis on the alveolar macrophage. Explanted cells from rabbit lung, spleen, peritoneum, bone marrow, and blood produced interferon in varying amounts in response to six of the seven viruses studied. The various lymphoreticular tissues responded differently to a single interferon-inducing virus, and each tissue produced varying amounts of interferon when stimulated by different viruses. In addition, glass-adherent rabbit alveolar macrophages produced more interferon than did the nonadherent subpopulation. Human blood and lung cells produced much less interferon than did the equivalent rabbit cells under similar conditions of stimulation. It appeared that interferon production may have been controlled by several variables, including the species, the type of inducer, and the type of tissue and cell.

Adult↗
PubMed1976

Interaction of nicotine and other amines with the endocytic and exocytic functions of macrophages.

Nicotine inhibits endocytosis and stimulates exocytosis in macrophages. At the same concentrations (5-15 mM) that the alkaloid exerts these effects, it is also vacuologenic. Consideration was given to one hypothesis that the membrane internalization was a result of surfactant activity. Nicotine was found to have surfactant properties. Studies involving measurements of the contact angles of a sessile drop of saline on cell monolayers suggested that nicotine increased the hydrophilicity of the membrane. The possibility has been considered that this may be indicative of membrane expansion and that this expansion leads to collapse and vesicle formation. This would be analogous to the effects of surface-active amines (e.g., local anesthetics, tranquilizers, antihistamines) on lipid monolayers and erythrocytic membranes. It is suggested that if such a mechanism does occur, then the possibility exists for a variety of amines to nonspecifically alter membrane and receptor availability of the macrophage.

Animals↗