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Biomedical subjects

Thomas A Cavalieri

Publications and source records attributed to Thomas A Cavalieri.

9 recordsLinked to original sources

Pifithrin-alpha attenuates p53-mediated apoptosis and improves cardiac function in response to myocardial ischemia/reperfusion in aged rats.

Ischemic cardiovascular disease is a common age-related disease. The p53-dependent cardiac myocyte apoptosis induced by myocardial ischemia/reperfusion (MI/R) is an important feature in the progression of ischemic heart disease. In the present studies, we hypothesized that inhibition of p53-dependent myocyte apoptosis may improve cardiac dysfunction in aged rats after MI/R. A dose (2.2 mg/kg, i.p.) of pifithrin-alpha (PFT), a p53 inhibitor, or saline was administered to 20-month-old male F344 rats, which were subjected to 30 min of myocardial ischemia by ligating the left main coronary artery, followed by release of the ligature and 4 h of reperfusion. Results of our experiments indicate that MI/R induced a significant decrease in cardiac output index (CI) and mean arterial blood pressure (MABP). Administration of PFT to aged rats 40 min before ischemia significantly improved CI and MABP during 3 to 4 h of reperfusion. The improvement of cardiac function was associated with a marked reduction in DNA fragmentation in the area at risk of the heart when compared with aged MI/R rats pretreated with saline. Interestingly, treatment with PFT 10 min after ischemia or 10 min after reperfusion had a similar protective effect on CI and MABP, but this effect did not reach statistical significance when compared with aged MI/R rats pretreated with saline. Treatment with PFT, however, did not influence plasma creatine kinase activity and the number of circulating leukocytes and infiltrated leukocytes in the area at risk of the heart. Moreover, results of Western blot show that pretreatment with PFT significantly attenuated the ratio of Bax to Bcl-2 in the area-at-risk tissue of the heart compared with that of rats pretreated with saline. Our results suggest that pretreatment with PFT significantly improved cardiac function. The mechanism of protective effect of PFT may involve the inhibition of p53 transcriptional function, thereby attenuating the p53/Bax-mediated myocyte apoptosis during the reperfusion period.

Animals↗

Attenuation of antioxidative capacity enhances reperfusion injury in aged rat myocardium after MI/R.

Mortality due to ischemic cardiovascular diseases is significantly higher in elderly than in young adults. Myocardial ischemia-reperfusion (MI/R) can induce oxidative stress and an inflammatory response. We hypothesized that increased vulnerability of aged myocardium to reperfusion injury could be caused by decreased antioxidative capacity, rather than increased oxidant production, after MI/R. Aged (20-mo-old) and young (4-mo-old) male F344BN rats were subjected to 30 min of myocardial ischemia by ligation of the left main coronary artery followed by release of the ligature and 4 h of reperfusion. Four experimental groups were studied: young sham-operated rats, aged sham-operated rats, young rats subjected to MI/R, and aged rats subjected to MI/R. MI/R significantly increased infiltrated leukocyte number and myeloperoxidase (MPO) activity in perinecrotic areas of hearts of young rats compared with aged MI/R rats. These changes in infiltrated leukocyte number and MPO activity were associated with an increase in superoxide generation in perinecrotic areas from hearts of young rats compared with aged rats. Plasma levels of TNF-alpha and IL-1beta were significantly higher in young than in aged MI/R rats. However, plasma 8-hydroxy-2'-deoxyguanosine levels and creatine kinase activity were increased in aged compared with young MI/R rats. Increased reperfusion damage in aged rats was associated with a significant decrease in plasma ratio of GSH to GSSG. Our results suggest that enhanced ischemia-reperfusion injury in aged rat hearts may be related to reduced antioxidative capacity, rather than increased reactive oxygen species production. These findings contribute to a better understanding of effects of aging on oxidative stress and inflammatory responses of the heart after MI/R.

8-Hydroxy-2'-Deoxyguanosine↗

Physicians' practices related to the use of terminal sedation: moral and ethical concerns.

OBJECTIVE: Although terminal sedation (TS) has generally been seen as legal and ethically acceptable, ethical and moral issues remain. Little is known about the use of TS in general clinical practice and about how TS is viewed by physicians, given moral and ethical concerns. The objectives of this study are (1) to describe attitudes of physicians regarding terminal sedation; (2) to explore demographic characteristics, such as age, gender, subspecialty, and number of years in practice, that might be related to the use of TS; and (3) to compare physicians who have and have not used TS on the degree to which they view TS as moral and consistent with their professional and personal ethics. METHODS: An anonymous survey of New Jersey physicians was conducted at the University of Medicine and Dentistry of New Jersey-School of Osteopathic Medicine. A 39-item questionnaire assessing general opinions about, experiences with, and religious, moral, ethical attitudes toward TS and other end-of-life treatments was utilized. RESULTS: A majority of physicians (73%) had used TS for a patient. Most (93%) said there were circumstances under which they would use TS. With regard to questions about whether TS would be "immoral," "would violate my religious beliefs," "would violate my professional ethics" and "is inconsistent with the physician's role of preserving life," approximately 55% of those who have used TS disagreed; for those who have not used TS, approximately 35% disagreed. SIGNIFICANCE OF RESULTS: Professional education and opportunities for discussion appear necessary to help reconcile the conflicts raised in the use of this end-of-life treatment strategy.

Adult↗

Predictive validity of osteopathic medical licensing examinations for osteopathic medical knowledge measured by graduate written examinations.

The purpose of this study was to evaluate the predictive validity of osteopathic medical licensing examinations for osteopathic medical knowledge measured by graduate written medical examinations. Performances on the three osteopathic initial licensing examinations, the three osteopathic internal medicine in-service examinations, and the osteopathic internal medicine board certification examinations were analyzed for a cohort of the most recent osteopathic internal medicine board certification examination candidates (N = 82). Multiple regressions were performed for the predictive value of licensing examination scores for the late examination scores. Logistic regressions were used for the prediction of pass/fail status on the licensing examinations for that on the board certification. A longitudinal performance profile was constructed to assess the rank changes in decile on the examinations at different times. All correlation coefficients between the licensing examinations and other examinations were significant and higher than .70. The licensing examinations together predicted at least 60% of the variance of any of the other examination scores. The pass/fail status on the licensing examinations predicted 89% of the pass/fail status on the certification examination. Decile ranks since the first licensing examination were consistent and stable over at least 5 years. The osteopathic licensing examinations had high predictive validity for the late written osteopathic internal medicine examinations. Generalization of the findings to other disciplines needs a caution, as a specialty bias may exist for these types of studies.

Educational Measurement↗

Age-related difference in myocardial function and inflammation in a rat model of myocardial ischemia-reperfusion.

OBJECTIVE: Aging is associated with a reduced tolerance to myocardial ischemia reperfusion injury when compared to the young adult. However, there is very little information in the literature regarding age-related changes in myocardial function and inflammation during myocardial ischemia-reperfusion (MI/R) in vivo. METHODS: We examined age-related differences in myocyte apoptosis and the inflammatory response in a rat model of myocardial ischemia-reperfusion (MI/R). The aged (19 months) and young (4 months) male F344 BN rats were subjected to 30 min of myocardial ischemia by ligating the left main coronary artery, followed by release of the ligature and 4 h of reperfusion. Four experimental groups, e.g. young sham control, aged sham control, young rats subjected to MI/R, and aged rats subjected to MI/R, were studied. RESULTS: MI/R induced a 78% increase in circulating leukocytes and a 30% increase in superoxide generation in the ischemic region of the heart of young rats, when compared to aged rats. Moreover, the arrhythmia scores were higher in young rats than in aged rats (P=0.058) following MI/R. There was no difference in hemodynamics between young sham and aged sham rats. However, the cardiac index was decreased by 34% at 3 h of reperfusion and by 33% at 4 h of reperfusion in aged rats, when compared to young rats following MI/R. Furthermore, stroke volume index was decreased by 54, 56, and 65% at 2, 3, and 4 h of reperfusion in aged rats, respectively, when compared that of young rats subjected to MI/R. There was an enhanced myocyte apoptosis, as indicated by ELISA and TUNEL staining in the myocardium of aged rats compared to young rats following MI/R. Interestingly, RT-PCR analysis indicated that MI/R significantly increased the ratio of Bax mRNA to Bcl-2 mRNA in aged rats compared to that of young rats (3.51 vs. 0.74). CONCLUSION: MI/R is associated with an increase in circulating leukocytes and generation of superoxide in the peri-ischemic areas of the heart of young rats, compared to aged rats. However, MI/R induces a significant decrease in cardiac index and stroke volume index in aged rats, when compared to young rats following MI/R. Furthermore, aged rats exhibit an increase in the ratio of Bax mRNA to Bcl-2 mRNA and cardiomyocyte apoptosis following MI/R, which may explain, at least in part, the enhanced myocardial dysfunction.

Aging↗

Attitudes of osteopathic physicians toward physician-assisted suicide.

The use of physician-assisted suicide (PAS) in the care of terminally ill patients is controversial. While there are published surveys assessing the attitudes and views of physicians in certain specialties, both nationally and in targeted geographic areas, no such data are available specifically pertaining to osteopathic physicians, who deliver 9% of the primary care in the United States. This article describes a study whose purpose was to identify the views and perspectives of osteopathic physicians on PAS through a national survey. Questionnaires were forwarded to all board-certified internists who are members of the American College of Osteopathic Internists and all surgeons and a random sample of family physicians who are members of the American Osteopathic Association. Physicians were surveyed with initial and follow-up mailings. The 49-item questionnaire was a modified version of the Physician Survey, Center for Ethics in Health Care: Oregon Health Sciences University. Of the 2910 questionnaires that were mailed, 1028 were returned in a usable form, for a 35% response rate. Respondents were predominantly (81%) male and from all parts of the country. Most (58%) would not be willing to prescribe a medication for a competent, terminally ill patient to use with the primary intention of ending his or her own life, and most (55%) would oppose the legalization of PAS. Thirty-three percent of osteopathic physicians admit to receiving requests by terminally ill patients for PAS. Most (53%) osteopathic physicians indicate that the osteopathic principle of holistic care has influenced their decision-making on this issue, and a significant minority (44%) responded that the osteopathic oath influenced their view on PAS. Religion and the degree of prayer frequency were important predictors of the decisions to support or oppose PAS. When compared to other physician surveys, this survey of osteopathic physicians demonstrates some similarities in response but also significant differences. These data suggest that osteopathic education and training may result in a perspective on PAS that reflects the distinctiveness of the osteopathic profession.

Adult↗

Osteoporosis prevention project: a model multidisciplinary educational intervention.

Osteoporosis is a systemic metabolic disease resulting in low bone mass, which increases the risk for fracture. Evidence suggests that lifestyle changes to prevent or delay development of osteoporosis should be implemented throughout the life span. The purpose of this study was to evaluate the effectiveness of a multidisciplinary primary osteoporosis prevention program for community-dwelling women aged 25 to 75 years to determine if osteoporosis prevention program participants (treatment group) increased their knowledge of osteoporosis, calcium intake, and exercise compared with a control group. Other outcomes included participants' willingness to adopt lifestyle changes and ability to view themselves as able to make behavioral changes. Subjects in the treatment group versus control subjects increased their knowledge of osteoporosis over time. At posttest, subjects in the treatment group were more likely to be planning to change calcium intake, and at follow-up, they were more likely to be changing their calcium intake. No other group differences were found between the two groups. These findings suggest that a multidisciplinary education program may have an impact on knowledge and behaviors that may help to delay the development of osteoporosis.

Adult↗

Pain management in the elderly.

Pain in the elderly is often unrecognized and undertreated. Ineffective pain management can have a significant impact on the quality of life of older adults, leading to depression, social isolation, and a loss of function. Proper assessment of older adults requires the physician to regularly ask about the presence of pain and be skillful in assessment strategies to evaluate the frequency and intensity of pain. Assessment of pain in older adults with dementia and communication disorders is especially challenging. Effective pain management in elderly patients should include both pharmacologic and nonpharmacologic strategies. Pharmacologic strategies call for administration of nonopioid analgesics, opioid analgesics, and adjuvant medication. Polypharmacy, drug-drug and drug-disease interactions, age-associated changes in drug metabolism, and the high frequency of adverse drug reactions need to be carefully considered in using medications in this population. Nonpharmacologic approaches such as cognitive-behavioral therapy, education, osteopathic manipulative treatment, and exercise should be applied in addition to pharmacologic therapy. Using a team approach and incorporating principles of pain management can effectively provide good analgesia for older adults.

Acetaminophen↗

How physicians approach advance care planning in patients with mild to moderate Alzheimer's disease.

Decision-making ability regarding end-of-life issues is often compromised by dementia in patients with Alzheimer's disease. This study assessed physicians' discussions of advance care planning with patients with mild to moderate Alzheimer's disease. Data were collected by a survey of full-time faculty in the departments of Medicine and Family Medicine and the Center for Aging at the University of Medicine and Dentistry of New Jersey-School of Osteopathic Medicine, as well as physicians in private practice affiliated with the Kennedy Health System. Data consisted of questions that assessed whether advance care planning was provided, what specific topics were discussed, and what actions were taken if advance care planning was not offered. Of the 271 physicians to whom the survey was sent, 63 responded, for a return rate of 23%. Of those responding, 81% indicated that they counseled their patients regarding advance care planning issues, while 19% did not. Of those who provided advance care planning for their patients (N = 51), 88% discussed living wills; 53%, the durable power of attorney for healthcare; 47%, end-of-life care; and 35%, financial planning issues. Thirty-seven percent recommended an elder law attorney, and 31% made a referral to the Alzheimer's Association. Of those who provided advance care planning for their patients' caregivers (N = 51), 86% discussed living wills; 78%, nursing home care; 69%, driving issues; and 47%, end-of-life care. Twenty-five percent referred their patients to an elder law attorney. Results indicate that physicians need to be more knowledgeable and proactive in their approaches to advance care planning for patients with mild to moderate Alzheimer's disease.

Advance Directives↗