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Biomedical subjects

C S Freeman

Publications and source records attributed to C S Freeman.

15 recordsLinked to original sources
PubMed1999

Heat stress activates production of herpes simplex virus type 1 from quiescently infected neurally differentiated PC12 cells.

We have previously described a novel in vitro model of a non-productive herpes simplex virus type 1 (HSV-1) infection in neurally differentiated (Nd)-PC12 cells that allows for inducible virus replication upon forskolin treatment. In this study, we further characterized the quiescent state of infection and examined the ability of heat stress (HS) to induce virus from this non-productive state. These studies demonstrated that (i) the quiescent state is characterized by the absence of cell-associated virus, capsids, and viral antigens; (ii) HS (43 degrees C, 3 h) efficiently activated virus from quiescently infected Nd-PC12 (QIF-PC12) cells; (iii) the rate of virus production was significantly greater following HS than forskolin treatment, and the rates of both were dependent on MOI; (iv) forskolin and HS appeared to affect pathways of viral activation from a quiescent state as they did not enhance viral growth in Nd-PC12 cells; (v) viral alpha4 gene and host HSP72 gene transcription were rapidly induced in QIF-PC12 as soon as 3 h post-HS initiation; (vi) induction of the viral alpha27 gene followed that of representative beta and gamma genes, U(L)30 and U(L)18, respectively, and (vii) HS induced asynchronous HSV-1 replication from QIF-PC12 cells with 1:400 to 1:22000 positive foci detected as rapid as 24 h post-induction when established at MOIs of 30 and 3, respectively. These findings provide evidence that alpha4 may be involved in the switch from quiescence to productive infection. Furthermore, this model has the potential to advance our understanding of how HS initiates the HSV-1 productive cycle from a cryptic viral genome.

Animals↗
PubMed1997

Follow-up of biologic monitoring results in cadmium workers removed from exposure.

Biological monitoring and exposure monitoring data for employees at a nickel-cadmium battery production facility were made available to OSHA for review. Sixteen employees were medically removed from occupational exposures to cadmium due to elevated levels of biological parameters (CdB, Cdu, B2U). While the biological monitoring parameters for most workers significantly declined during the 18 months of medical removal, the biological parameters for only one employee's values returned to the normal range. Only one worker had frank renal dysfunction, based on beta-2-microglobulin levels at the time of removal; this dysfunction remained throughout the 17 months of observation after medical removal. Significant policy implications of medical removal protection beyond the current 18-month period provided by the cadmium standards exist and require physician discretion. Mitigating issues which may make it ethically appropriate to return an employee to work despite elevated biologic monitoring parameters are also discussed.

Cadmium↗
PubMed1996

Biological monitoring results for cadmium exposed workers.

As part of a settlement agreement with the Occupational Safety and Health Administration (OSHA) involving exposure to cadmium (Cd), a battery production facility provided medical surveillance data to OSHA for review. Measurements of cadmium in blood, cadmium in urine, and beta 2-microglobulin in urine were obtained for more than 100 workers over an 18-month period. Some airborne Cd exposure data were also made available. Two subpopulations of this cohort were of primary interest in evaluating compliance with the medical surveillance provisions of the Cadmium Standard. These were a group of 16 workers medically removed from cadmium exposure due to elevations in some biological parameter, and a group of platemakers. Platemaking had presented a particularly high exposure opportunity and had recently undergone engineering interventions to minimize exposure. The effect on three biological monitoring parameters of medical removal protection in the first group and engineering controls in platemakers is reported. Results reveal that both medical removal from cadmium exposures and exposure abatement through the use of engineering and work practice controls generally result in declines in biological monitoring parameters of exposed workers. Implications for the success of interventions are discussed.

Air Pollutants, Occupational↗
PubMed1995

Silica exposures in workplaces in the United States between 1980 and 1992.

Between 1980 and 1992, compliance officers of the Occupational Safety and Health Administration in the United States measured respirable quartz in 1655 inspections in 255 industries. In 52% of the 255 industries where respirable quartz was measured, the average severity value was less than one, indicating average exposures below the permissible exposure limit, and in 48% the permissible exposure limit for silica was exceeded. Among industries where more than 10 facilities were inspected, the most severe respirable quartz exposures were found in fabricated structural metal; painting and paper hanging; nonresidential construction; shipbuilding and repair; masonry and other stone work; bridge, tunnel and elevated highway construction; metal coating, engraving and allied services; and special trades contractors.

Humans↗
PubMed1994

High-risk occupations for women exposed to cadmium.

Occupational exposures to cadmium are associated with increased risk of lung cancer and renal disease. The Occupational Safety and Health Administration (OSHA) published two standards for cadmium on September 14, 1992 that reduced the permissible occupational exposure limit. In the cadmium industry, women were less likely to be exposed to high levels of cadmium and more likely to hold job titles containing the word "hand" than were men. Only small numbers of female workers were exposed to any level of cadmium. OSHA's risk assessment relied, in part, on morbidity and mortality data from male workers and in part on rodent (animal) data from both sexes. OSHA did not evaluate illness rates specific to female workers. Several factors may alter the risk of these illnesses and their sequelae among workers, including differences in smoking, route of exposures, ability to wear personal protective equipment, and lifestyle.

Cadmium↗
PubMed1990

Surgical coronary revascularization in survivors of prehospital cardiac arrest: its effect on inducible ventricular arrhythmias and long-term survival.

In a selected subgroup of 50 survivors of cardiac arrest, the impact of surgical myocardial revascularization on inducible arrhythmias, arrhythmia recurrence and long-term survival was examined. The effects of several clinical, angiographic and electrophysiologic variables on arrhythmia recurrence and survival were also analyzed. All patients had a prehospital cardiac arrest and severe operable coronary artery disease and underwent myocardial revascularization. Preoperative electrophysiologic study was performed in 41 patients; 33 (80%) had inducible ventricular arrhythmias. Of 42 patients studied off antiarrhythmic drugs postoperatively, 19 (45%) had inducible ventricular arrhythmias. Thirty patients with inducible arrhythmias preoperatively underwent postoperative testing off antiarrhythmic drugs; arrhythmia induction was suppressed in 14 (47%). By multivariate analysis, the induction of ventricular fibrillation at the preoperative electrophysiologic study was the only significant predictor of induced ventricular arrhythmia suppression by coronary surgery (p less than 0.001). Inducible ventricular fibrillation was not present postoperatively in any of the 11 patients who manifested this arrhythmia preoperatively. In contrast, inducible ventricular tachycardia persisted in 80% of patients in whom preoperative testing induced this arrhythmia. Patients were followed up for 39 +/- 29 months. There were four arrhythmia recurrences; one was fatal. There were three nonsudden cardiac deaths and three noncardiac deaths. By life-table analysis, 5 year survival, cardiac survival and arrhythmia-free survival rates were 88%, 98%, and 88%, respectively. Depressed left ventricular ejection fraction and advanced age were predictive of death (p = 0.015 and 0.026, respectively) and cardiac death (p = 0.037 and 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1989

Cardiac conduction abnormalities during percutaneous balloon mitral or aortic valvotomy.

To evaluate the electrophysiologic changes in the cardiac conduction system that occur during percutaneous mitral or aortic balloon valvotomy, we prospectively studied the conduction system in 19 patients (10 mitral, 8 aortic, and 1 both) undergoing this procedure. A His bundle electrogram was recorded in all patients, and when sinus rhythm was present, the atrioventricular (AV) node effective refractory period was measured. Holter monitoring was performed during and for 24 hours after the procedure. Follow-up electrocardiograms (ECG) were available in 11 patients 2.3 +/- 1.5 months after the procedure. The AV node effective refractory period before (276 +/- 86 msec) and after valvotomy (298 +/- 85 msec) were not significantly different. The maximum His-Purkinje conduction time (HV interval) observed during valvotomy (66 +/- 20 msec) was significantly longer (p less than 0.01) than that measured before (57 +/- 10 msec) or after (60 +/- 18 msec) valvotomy. The mean HV intervals before and after valvotomy were not significantly different. The mean QRS complex duration increased from 95 +/- 28 to 112 +/- 28 msec during valvotomy and remained significantly prolonged (109 +/- 26 msec) 24 hours after the procedure (p less than 0.01). A new intraventricular conduction defect (QRS complex duration greater than 100 msec) or bundle branch block occurred in five of 13 patients who had normal QRS duration before the procedure. The change in HV interval did not correlate with the change in QRS complex duration. In four patients, the newly acquired intraventricular conduction defect was still present on follow-up ECG tracing. Complete heart block was not observed in any patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Sensitivity of an automatic external defibrillator for ventricular tachyarrhythmias in patients undergoing electrophysiologic studies.

An automatic advisory external defibrillator (AED) was activated during all arrhythmias occurring at the time of 77 electrophysiologic studies in 45 patients. Sustained ventricular tachycardia (VT) occurred during 55 studies in 31 patients and nonsustained VT was induced during 10 studies in 9 patients. Ventricular fibrillation was induced 5 times in 5 patients and atrial arrhythmias with a rapid ventricular response occurred during 7 studies in 4 patients. The AED detection algorithm advised "shock" during 36 of 55 (65%) episodes of sustained VT and all 5 episodes of ventricular fibrillation. The device correctly advised "shock" for all 6 episodes of nonsustained VT that spontaneously terminated after analysis was complete. Thus, the sensitivity of the device for all ventricular arrhythmias analyzed was 47 of 66 (71%). The device recommended "shock" for all 31 episodes of rapid VT and 1 of 2 episodes of atrial fibrillation associated with systemic hypotension (32 of 33, 97%). The 19 episodes of VT for which "no shock" was advised were comparatively slow and were hemodynamically well tolerated. The device recommended "no shock" during all 21 episodes of normal sinus rhythm and all 20 episodes of rapid atrial pacing (cycle length 400 ms) analyzed. "No shock" was advised during 4 episodes of sustained narrow QRS complex supraventricular tachycardia and 4 brief episodes of nonsustained VT that terminated before analysis was complete. Thus, in this study the specificity of the AED for wide complex tachycardias was 100%.

Algorithms↗
PubMed1988

Prediction of successful suppression of sustained ventricular tachyarrhythmias by serial drug testing from data derived at the initial electrophysiologic study.

This study investigated whether data available after the initial electrophysiologic study in patients with sustained ventricular tachyarrhythmia could identify those patients in whom serial drug testing is likely to be efficacious. One hundred six patients with inducible sustained ventricular tachyarrhythmia, whose initial study included short-term drug testing with intravenous procainamide, were evaluated. The baseline arrhythmia induced (in the absence of all antiarrhythmic drugs) was monomorphic tachycardia with a cycle length greater than 200 ms in 81 patients and ventricular flutter or fibrillation in the remaining 25 patients. After intravenous infusion of procainamide (1,250 +/- 300 mg), a ventricular tachyarrhythmia could still be induced in 80 patients during testing with up to three extrastimuli. Serial drug testing with one to four trials of oral conventional and investigational agents was then undertaken. Evaluation of 15 clinical, hemodynamic and electrophysiologic variables by stepwise logistic regression identified two independent predictors of successful response to oral antiarrhythmic drugs: 1) noninducibility of ventricular tachycardia after intravenous procainamide (p less than 0.001), and 2) left ventricular ejection fraction greater than or equal to 40% (p less than 0.05). Subgroup analysis combining each of these variables identified patients with a high, intermediate or low probability of finding a successful oral drug regimen. Patients whose arrhythmia was suppressed by intravenous procainamide had a 100% likelihood (if left ventricular ejection fraction was greater than or equal to 40%) or an 87% likelihood (if ejection fraction was less than 40%) of responding to an oral regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1978

Progesterone is not essential to the differentiative potential of mammary epithelium in the male mouse.

In pursuit of a model system in which to determine whether or not exposure to progesterone is necessary for mammary epithelial cells to develop their differentiative potential, we explored hormone-dependent growth of the mammary epithelial rudiment in adult male mice. Initiation of the formation of ductal cells can be effected by administration of estradiol in the absence of endogenous progesterone and glucocorticoid using adrenalectomized-castrated animals. The resulting epithelium contains three times more lactose synthetase activity per epithelial cell than that in midpregnant mice. The blood spermidine level in these doubly operated animals was similar to the concentration of spermidine required to substitute effectively for glucocorticoid during mammary differentiation in vitro. It is suggested that spermidine can partially supplant glucocorticoid in vivo in milk protein synthesis. We also concluded that, unlike other secondary sex tissues, mammary cells do not require exposure to progesterone during their ontogeny in order to realize their differentiative potential. The positive role of this steroid in mammary development is apparently limited to its effect on the formation of alveolar structures.

Adrenalectomy↗
PubMedDate not supplied

Progesterone and glucocorticoid in relation to the growth and differentiation of mammary epithelium.

In pursuit of a model system in which to determine whether exposure to progesterone is necessary for mammary epithlial cells to develop their differentiative potential, hormone-dependent growth of the mammary epithelial rudiment in adult male mice has been reexplored. The formation of ductal cells can be effected by administration of estradiol in the absence of endogenous progesterone and glucocorticoid, using adrenalectomized-castrated animals. The resulting epithlium contains three times more lactose synthetase activity, per epithelial cell, than that in midpregnant mice. The blood spermidine level in these doubly operated animals was similar to the concentration of spermidine required to substitute effectively for glucocorticoid during mammary differentiation in vitro, It is suggested that spermidine can partially supplant glucocorticoid in vivo in milk protein synthesis. It is also concluded that, unlike other secondary sex tissues, mammary cells do not require exposure to progesterone during their ontogeny in order to realize their differentiative potential. The positive role of this steroid in mammary development is apparently limited to its effect on the formation of alveolar structures.

Adrenalectomy↗