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Biomedical subjects

B Drew

Publications and source records attributed to B Drew.

At least 19 recordsLinked to original sources

Ageing and subcellular distribution of mitochondria: role of mitochondrial DNA deletions and energy production.

The rapid growing population of elderly illustrates the importance of understanding the mechanisms responsible for ageing and the detrimental effects on health associated with increasing age. One of the primary mechanisms may be because of the accumulation of mtDNA damage and oxidative damage with age. Previous studies have examined this correlation in post-mitotic tissues such as skeletal muscle, heart and brain with decreased mitochondrial function, such as enzymatic activities of the electron transport chain and ATP production. However, regional differences in the subcellular location of mitochondria exist and most studies have failed to differentiate the effects of these two autonomous fractions, the subsarcolemmal and intermyofibrillar populations. Hence, while future research attempts to explain the mechanisms responsible for ageing in the mitochondrion, it should also take into account the independent pathways of these two distinctly different populations.

Adenosine Triphosphate↗

Effects of aging and caloric restriction on mitochondrial energy production in gastrocnemius muscle and heart.

Mitochondria are chronically exposed to reactive oxygen intermediates. As a result, various tissues, including skeletal muscle and heart, are characterized by an age-associated increase in reactive oxidant-induced mitochondrial DNA (mtDNA) damage. It has been postulated that these alterations may result in a decline in the content and rate of production of ATP, which may affect tissue function, contribute to the aging process, and lead to several disease states. We show that with age, ATP content and production decreased by approximately 50% in isolated rat mitochondria from the gastrocnemius muscle; however, no decline was observed in heart mitochondria. The decline observed in skeletal muscle may be a factor in the process of sarcopenia, which increases in incidence with advancing age. Lifelong caloric restriction, which prolongs maximum life span in animals, did not attenuate the age-related decline in ATP content or rate of production in skeletal muscle and had no effect on the heart. 8-Oxo-7,8-dihydro-2'-deoxyguanosine in skeletal muscle mtDNA was unaffected by aging but decreased 30% with caloric restriction, suggesting that the mechanisms that decrease oxidative stress in these tissues with caloric restriction are independent from ATP availability. The generation of reactive oxygen species, as indicated by H2O2 production in isolated mitochondria, did not change significantly with age in skeletal muscle or in the heart. Caloric restriction tended to reduce the levels of H2O2 production in the muscle but not in the heart. These data are the first to show that an age-associated decline in ATP content and rate of ATP production is tissue specific, in that it occurs in skeletal muscle but not heart, and that mitochondrial ATP production was unaltered by caloric restriction in both tissues.

Adenosine Triphosphate↗

End-of-life issues in intensive care units: a national random survey of nurses' knowledge and beliefs.

OBJECTIVE: To investigate the knowledge, beliefs, and ethical concerns of nurses caring for patients dying in intensive care units. METHODS: A survey was mailed to 3000 members of the American Association of Critical-Care Nurses. The survey contained various scenarios depicting end-of-life actions for patients: pain management, withholding or withdrawing life support, assisted suicide, and voluntary and nonvoluntary euthanasia. RESULTS: Most of the respondents (N = 906) correctly identified the distinctions among the end-of-life actions depicted in the scenarios. Almost all (99%-100%) agreed with the actions of pain management and withholding or withdrawing life support. A total of 83% disagreed with assisted suicide, 95% disagreed with voluntary euthanasia, and 89% to 98% disagreed with nonvoluntary euthanasia. Most (78%) thought that dying patients frequently (31%) or sometimes (47%) received inadequate pain medicine, and almost all agreed with the double-effect principle. Communication between nurses and physicians was generally effective, but unit-level conferences that focused on grief counseling and debriefing staff rarely (38%) or never (49%) occurred. Among the respondents, 37% had been asked to assist in hastening a patient's death. Although 59% reported that they seldom acted against their consciences in caring for dying patients, 34% indicated that they sometimes had acted against their conscience, and 6% had done so to a great extent. CONCLUSIONS: Intensive care unit nurses strongly support good pain management for dying patients and withholding or withdrawing life-sustaining therapies to allow unavoidable death. The vast majority oppose assisted suicide and euthanasia. Wider professional and public dialogue on end-of-life care in intensive care units is warranted.

Adult↗

Upper airway complications in children after bone marrow transplantation.

OBJECTIVE: To describe the upper and lower airway complications in children during bone marrow transplantation (BMT). STUDY DESIGN: Review of medical records of patients requiring airway intervention during BMT over a 4-year period. RESULTS: During the 4-year period, 832 pediatric BMTs were performed. Of these, 87 patients (10.5%) required mechanical ventilation. Patients had intubation for a mean of 79 days (range, -7-638 d) after BMT. Patients received mechanical ventilation for a mean of 12 days (range, 1-85 d). Duration of ventilation was significantly longer in patients with difficult intubation; in these 54 patients there were 64 intubations. Of these intubations, 19 (30%) were difficult. These difficult intubations occurred in 16 (30%) patients. Patients with Hurler syndrome and congenital immunodeficiencies had significantly more difficult intubations than children with leukemia. The incidence of complications causing difficult intubation were difficulty visualizing cords, because of the presence of blood (63%); difficulty visualizing cords, because of edema (19%); anatomically narrowed airway (13%); limited neck extension (13%); and limited jaw opening (6%). The resulting mortality rate was 82% in children requiring intubation. Survivors were significantly younger than nonsurvivors. CONCLUSIONS: Pediatric BMT has become increasingly more common. Airway management is rarely required during the engraftment phase, but when intervention is required, it is often difficult, particularly in the nonleukemic child, and may require the skills of an otolaryngologist. Representative cases are presented, and management is discussed.

Adolescent↗

Field trial of a planned breeding regimen for dairy cows, using gonadotrophin-releasing hormone and prostagladin F2alpha.

A planned breeding regimen, using gondadotrophin-releasing hormone (GnRH), prostaglandin F2alpha, and a second dose of GnRH, followed by a fixed time insemination, was evaluated in comparison with a negative control on eight commercial dairy farms in the south of England. Fertility data were collected from the 220 cows in the planned breeding group and from 220 matched control cows inseminated at observed oestrus. The planned regimen induced visible oestrus in the vast majority of the cows, and serving the cows at this oestrus reduced the calving to conception interval by 15 days, resulting in 12 per cent more cows being pregnant by 125 days after calving, and 6 per cent more by 150 days. The results from the individual farms suggested that more benefit may be derived from using the regimen in herds with only average fertility indices. There was also evidence to suggest that the second GnRH injection was important, even in cows that came on heat and were served before the fixed time insemination.

Animals↗

Comparison of 18-lead ECG and selected body surface potential mapping leads in determining maximally deviated ST lead and efficacy in detecting acute myocardial ischemia during coronary occlusion.

Kornreich identified 6 body surface potential mapping (BSPM) leads outside the standard 12-lead electrocardiographic (ECG) sites for optimal recognition of ST segment elevation (+) and depression (-) during acute ischemia in anterior, inferior, and posterior myocardial zones (A+, A-, I+, I-, P+, P-). No comparison has been made between the 6 selected BSPM leads and 18-lead ECG (12 + V3-5R + V7-9) in detecting acute myocardial ischemia during coronary occlusion. Continuous 18-lead ECG and 6 selected BSPM leads were recorded in 68 patients (77 vessels) undergoing coronary angioplasty during balloon occlusion. Ischemia was defined as ST segment deviation (deltaST) > or = 100 microV > or = 1 lead from the preinflation baseline. The 18-lead ECG was a more frequent source of the maximal deltaST lead during left anterior descending artery, right coronary artery, and left circumflex artery occlusion (71 [92%]) than the 6 selected BSPM leads (5 [7%]). The 18-lead ECG was more efficacious than the 6 selected BSPM leads for detecting acute myocardial ischemia in the group as whole. The 18-lead ECG was also more efficacious for detecting right ventricular ischemia associated with proximal right coronary artery occlusion and for detecting ST segment elevation during left circumflex artery occlusion. Our findings indicate that the 18-lead ECG is the most frequent source of maximally deviated lead and is more efficacious in detecting myocardial ischemia during balloon occlusion than the 6 selected BSPM leads. The 6 selected BSPM leads do not add information above and beyond the 12- or 18-lead ECG, and thus cannot be recommended as optimal sites for continuous ST segment monitoring of patients with acute coronary syndromes.

Aged↗

The utilization of automated ST segment analysis in the determination of myocardial ischemia.

Perioperative cardiac morbidity is a recognized complication of anesthesia and surgery. Morbidity includes myocardial infarction, new onset of unstable angina, congestive heart failure, and arrhythmias. Almost one third of all patients undergoing noncardiac surgery may be at increased risk of cardiac complications by virtue of age, coronary artery disease (CAD), or presence of two or more risk factors for CAD. Although postoperative ischemia has been identified as a significant risk factor for morbidity, automated ST segment analysis systems available with the new generation bedside monitors have not been used to identify ischemic episodes in patients recovering from anesthesia. Twenty-eight patients, age 41 to 80 years, were monitored in the postanesthesia care unit for ST segment changes (mean monitoring period, 97 minutes). Four patients had ischemic episodes from 7 to 44 minutes, and two of these patients had subsequent postoperative morbidity. All episodes were clinically silent. Automated ST segment analysis is an easily used technology that shows promise as a means of early detection of clinically silent perioperative myocardial ischemia.

Adult↗

Multiple genes encode the major surface glycoprotein of Pneumocystis carinii.

The major surface antigen of Pneumocystis carinii, a life-threatening opportunistic pathogen in human immunodeficiency virus-infected patients, is an abundant glycoprotein that functions in host-organism interactions. A monoclonal antibody to this antigen is protective in animals, and thus this antigen is a good candidate for development as a vaccine to prevent or control P. carinii infection. We have cloned and sequenced seven related but unique genes encoding the major surface glycoprotein of rat P. carinii. Partial amino acid sequencing confirmed the identity of these genes. Based on Southern blot studies using chromosomal or restricted DNA, the major surface glycoproteins are the products of a multicopy family of genes. The predicted protein has an M(r) of approximately 123,000, is relatively rich in cysteine residues (5.5%) that are very strongly conserved, and contains a well conserved hydrophobic region at the carboxyl terminus. The presence of multiple related msg genes encoding the major surface glycoprotein of P. carinii suggests that antigenic variation is a possible mechanism for evading host defenses. Further characterization of this family of genes should allow the development of novel approaches to the control of this pathogen.

Amino Acid Sequence↗

The effect of excess dietary iodine on pregnant mares and foals.

On a thoroughbred stud four foals were born with greatly enlarged thyroids and leg weakness. Two foals died within 18 hours of birth, the others subsequently recovered. An enlarged thyroid was also evident in one of the resident mares. The thyroids from the dead foals were hyperplastic. Feed analyses showed that the mares had an iodine intake of about 83 mg daily, 8-8 ppm of the dietary dry matter, due almost entirely to the high iodine content of a proprietary compound horse nut which had been fed at the daily rate of 12 lb per head. It was concluded from the histology of the thyroids, the high intake of iodine, the lack of response to treatment with potassium iodide and the elevated levels of serum protein bound iodine that the condition of the foals on the stud was caused by an excess of iodine fed to the mares during pregnancy.

Animal Feed↗