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Biomedical subjects

Gregory Engel

Publications and source records attributed to Gregory Engel.

8 recordsLinked to original sources

Genetic characterization of rhesus macaques (Macaca mulatta) in Nepal.

Indian-origin rhesus macaques (Macaca mulatta) have long served as an animal model for the study of human disease and behavior. Given the current shortage of Indian-origin rhesus, many researchers have turned to rhesus macaques from China as a substitute. However, a number of studies have identified marked genetic differences between the Chinese and Indian animals. We investigated the genetic characteristics of a third rhesus population, the rhesus macaques of Nepal. Twenty-one rhesus macaques at the Swoyambhu Temple in Kathmandu, Nepal, were compared with more than 300 Indian- and Chinese-origin rhesus macaques. The sequence analyses of two mitochondrial DNA (mtDNA) loci, from the HVS I and 12 S rRNA regions, showed that the Nepali animals were more similar to Indian-origin than to Chinese-origin animals. The distribution of alleles at 24 short tandem repeat (STR) loci distributed across 17 chromosomes also showed greater similarity between the Nepali and Indian-origin animals. Finally, an analysis of seven major histocompatibility complex (MHC) alleles showed that the Nepali animals expressed Class I alleles that are common to Indian-origin animals, including Mamu-A*01. All of these analyses also revealed a low level of genetic diversity within this Nepali rhesus sample. We conclude that the rhesus macaques of Nepal more closely resemble rhesus macaques of Indian origin than those of Chinese origin. As such, the Nepali rhesus may offer an additional resource option for researchers who wish to maintain research protocols with animals that possess key genetic features characteristic of Indian-origin rhesus macaques.

Animals↗

Risk assessment: A model for predicting cross-species transmission of simian foamy virus from macaques (M. fascicularis) to humans at a monkey temple in Bali, Indonesia.

Contact between humans and nonhuman primates (NHPs) frequently occurs at monkey temples (religious sites that have become associated with free-ranging populations of NHPs) in Asia, creating the potential for NHP-human disease transmission. In March 2003 a multidisciplinary panel of experts participated in a workshop designed to model the risk of NHP-human pathogen transmission. The panel developed a risk assessment model to describe the likelihood of cross-species transmission of simian foamy virus (SFV) from temple macaques (Macaca fascicularis) to visitors at monkey temples. SFV is an enzootic simian retrovirus that has been shown to be transmitted from NHPs to humans. In operationalizing the model field data, laboratory data and expert opinions were used to estimate the likelihood of SFV transmission within this context. This model sets the stage for a discussion about modeling as a risk assessment tool and the kinds of data that are required to accurately predict transmission.

Animals↗

Electrocardiographic damage scores and cardiovascular mortality.

BACKGROUND: A number of electrocardiogram (ECG) classification systems have been developed to estimate cardiac injury, infarct size, and left ventricular function. Although many studies have documented an association between clinical, imaging, and autopsy data, few have evaluated their prognostic value. METHODS AND RESULTS: ECGs from 46,933 patients were analyzed using computerized measurements and algorithms. The Simplified Selvester Score, the Cardiac Infarction Injury Score (CIIS), and a Q-wave score were calculated. Other ECG characteristics such as left ventricular hypertrophy and bundle-branch blocks were also evaluated. The main outcome was cardiovascular (CV) mortality. During a mean follow-up of 6 years, the CIIS outperformed all other ECG classifications in determining prognosis. Going from lowest to highest tertile of CIIS, each step had a hazard ratio of 1.39 (CI 1.32-1.45) or a 39% increase in risk per tertile. Using clinically based thresholds, the annual mortality for high-risk CIIS was 4.5% (CI 4.0-4.6) versus 0.3% (CI 0.0-1.3) for those in the low-risk group. CONCLUSIONS: A low-risk damage score was associated with a <1% annual CV mortality and a high-risk damage score with annual CV mortality of >4%. A damage score should be calculated as part of all computerized ECG interpretations.

Aged↗

Treprostinil for the treatment of severe digital necrosis in systemic sclerosis.

We report a case of severe digital ulcerations associated with systemic sclerosis, successfully treated with treprostinil (Remodulin). There was improvement within days of the treatment initiation; complete healing was accomplished after 16 weeks of therapy. Patients with systemic sclerosis and peripheral small vessel disease have limited therapeutic options. Treprostinil is a prostacyclin analogue that can be delivered by subcutaneous infusion and is approved in the USA only for treatment of primary pulmonary hypertension. This report provides an impressive example of an alternative, complementary indication for the use of treprostinil.

Adult↗

Electrocardiographic arrhythmia risk testing.

Among the most compelling challenges facing cardiologists today is identification of which patients are at highest risk for sudden death. Automatic implantable cardioverter-defibrillators are now indicated in many of these patients, yet the role of noninvasive risk stratification in classifying patients at high risk is not well defined. The purpose of this review is to evaluate the various electrocardiographic (ECG) techniques that appear to have potential in assessment of risk for arrhythmia. The resting ECG (premature ventricular contractions, QRS duration, damage scores, QT dispersion, and ST segment and T wave abnormalities), T wave alternans, late potentials identified on signal-averaged ECGs, and heart rate variability are explored. Unequivocal evidence to support the widespread use of any single noninvasive technique is lacking; further research in this area is needed. It is likely that a combination of risk evaluation techniques will have the greatest predictive power in enabling identification of patients most likely to benefit from device therapy.

Arrhythmias, Cardiac↗

Pituitary apoplexy after leuprolide injection for ovum donation.

Patients with occult pituitary adenomas infrequently present with pituitary apoplexy. Precipitation of pituitary apoplexy by gonadotropin releasing hormone or gonadotropin releasing hormone agonists has been described. The pathophysiologic mechanism by which these agents induce apoplexy remains unclear. We describe a case of pituitary apoplexy in a young woman receiving leuprolide in preparation for ovum donation. Severe hyponatremia, cerebral vasospasm and infarction, and diabetes insipidus complicated this patient's prolonged hospital course. To our knowledge, pituitary apoplexy after gonadotropin releasing hormone agonist use for ovum donation has not been previously described. The use of leuprolide or other gonadotropin releasing hormone agonists for pituitary down-regulation in conjunction with ovarian stimulation can have serious consequences in women harboring unrecognized pituitary adenomas. Thorough endocrine screening should be performed prior to initiating therapy.

Adult↗