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T McDonald

Publications and source records attributed to T McDonald.

At least 37 records · Page 2Linked to original sources

Identification of two hERR2-related novel nuclear receptors utilizing bioinformatics and inverse PCR.

Identification of novel nuclear receptors based on the highly conserved DNA-binding domain (DBD) has previously depended mainly on low stringency hybridization of cDNA libraries and degenerate PCR. Establishment of the expressed sequence tag (EST) database in recent years has provided an alternative approach for the discovery of novel members of gene families. The rate-limiting step is the conversion of ESTs to full-length cDNA. This article describes the identification of two novel nuclear receptors (hERRbeta2 and hERRgamma2) related to human estrogen-receptor-related receptor 2 (hERR2) by mining the EST database and retrieving of full-length cDNA via inverse PCR on subdivided primary cDNA library pools. The deduced protein sequences of hERRbeta2 and hERRgamma2 contain 500 and 458 amino acid (aa) residues respectively. Sequence analysis revealed that hERRbeta2 and hERRgamma2 respectively share 95% and 77% overall aa sequence identity with hERR2. However, the extra C-terminal domain in hERRbeta2 and extra N-terminal domain in hERRgamma2 are not present in the closely related hERR2 or mouse ERR2 (mERR2). Extensive sequence verification revealed that hERR2 previously reported as a human gene is actually a rat gene, whereas hERRbeta2 is the true human ortholog of hERR2 and mERR2. Tissue distribution studies showed that hERRgamma2 was expressed in a broader panel of tissues at a higher level than hERRbeta2. hERRbeta2 was mapped to cytogenetic locus 14q24.3 approximately -14q31, a region containing multiple loci involved in genetic diseases, including Alzheimer and diabetes. hERRgamma2 was mapped to 1q32. Given the high sequence homology between hERRbeta2 and mERR2, the two receptors may have similar biological function in vivo.

Amino Acid Sequence↗

Perioperative rehydration in ambulatory anesthesia for dentoalveolar surgery.

OBJECTIVE: Patient recovery after anesthesia is dependent not only on the lingering pharmacologic effects of sedatives but also on the physiologic effects that patients experience after surgery. Preoperative fasting results in a perioperative dehydration that may contribute to these physiologic effects, resulting in complaints of headache, nausea, vomiting, fatigue, lightheadedness, dizziness, and thirst. The purpose of this study was to investigate the effects of perioperative hydration in the ambulatory oral and maxillofacial surgery patient who receives deep sedation or general anesthesia (nonintubated). STUDY DESIGN: This was a prospective, randomized, blinded study that administered either a high volume (16-17 mL/kg) or a low volume (1-2 mL/kg) of an isotonic solution to each of 77 patients who were scheduled to have their third molars extracted with deep sedation or general anesthesia. Each patient completed 3 postoperative questionnaires designed to evaluate potential adverse outcomes. RESULTS: Nonparametric analysis of the data demonstrated a more favorable outcome with respect to subjective feelings for the high volume hydration group; this was evident both during the immediate postoperative period and in the evening of the day of surgery, and it persisted into the first postoperative day. CONCLUSIONS: This study demonstrated that appropriate perioperative rehydration decreases postoperative adverse outcomes and improves the patient's perception of the postoperative period.

Ambulatory Surgical Procedures↗

Determinants of participation in an epidemiological study of preterm delivery.

We describe the study design and patterns of participation for a cohort study of preterm delivery, focused on genital tract infections, nutrition, tobacco use, illicit drugs and psychosocial stress. Women are recruited at 24-29 weeks' gestation from prenatal clinics at a teaching hospital and a county health department. We recruited 57% of the first 1843 eligible women; 29% refused and 8% could not be contacted. White women were somewhat more likely to participate than African-American women (61% vs. 54% respectively). More notable differences were found comparing teaching hospital and health department clinics (71% vs. 47% participation respectively), with the health department clinic having a greater proportion refuse (24% vs. 33%) and more women who could not be contacted (4% vs. 11%). Participation was affected only minimally by day or timing of recruitment, but inability to contact diminished substantially as the study continued (13-0%). Refusals were largely unrelated to patient attributes. Lower education predicted inability to contact. Risk of preterm delivery was 14% among recruited women, 10% among women who refused, and 15% among women whom we were not able to contact, demonstrating that, overall, risk status was not lower among recruited women.

Adolescent↗

Heart rate variability and plasma catecholamines in patients during opioid detoxification.

It has been shown that rapid opioid detoxification is associated with increased sympathetic activity (SYMP) and plasma catecholamines. Heart rate (HR) variability may provide a noninvasive method of evaluating withdrawal and sympathetic activation caused by the reversal of opioid binding in patients who are opioid dependent. The purpose of this study was to evaluate the relationship between HR variability and plasma catecholamines during opioid detoxification. Patients were anesthetized with propofol, intubated, paralyzed with rocuronium infusion, and ventilated. The bispectral index (BIS) of the electroencephalogram was recorded with the patient awake as well as during propofol anesthesia. SYMP was determined by power spectral analysis of HR variability. Plasma epinephrine and norepinephrine were measured at baseline propofol anesthesia and during naltrexone treatment in eight opioid-dependent patients. Nonopioid-dependent controls (n = 7) were monitored during surgery without naltrexone treatment or measurement of plasma catecholamines. Compared with an awake status, propofol anesthesia significantly decreased the BIS and SYMP in both groups of patients. Controls showed no change from baseline anesthetized levels during surgery. Plasma norepinephrine and epinephrine as well as SYMP increased 300 to 400% (P < .05) during naltrexone treatment in opioid-dependent patients, and the time to peak increase in plasma norepinephrine correlated with the increase in SYMP (r = 0.89, P < .01). These results confirm that opioid detoxification increases plasma catecholamines and SYMP in a similar manner. HR rate variability may provide a low-cost real-time noninvasive method of evaluating the reversal of opioid binding in opioid-dependent patients.

Adult↗

Median EEG frequency is more sensitive to increases in sympathetic activity than bispectral index.

Sympathetic heart rate variability is correlated with the increase in plasma catecholamines during rapid opioid detoxification. We evaluated whether the bispectral index, median frequency, or 95% spectral edge of the electroencephalogram are sensitive to the sympathetic response seen during reversal of opioid dependence. Eight patients undergoing rapid opioid detoxification gave informed consent. Two-channel frontal electroencephalogram was measured. Sympathetic heart rate variability was measured in 256 second segments by Fourier transform of continuous heart rate and the low frequency segment (0.02-0.13 Hz) analyzed for sympathetic function. Patients were anesthetized with propofol infusion. After a 30-60 min steady state, naloxone was infused intravenously at a rate of 25 mg/30 min, followed by an infusion of 1 mg/hr. During induction of anesthesia, sympathetic heart rate variability decreased from 1.80 to 0.3, bispectral index from 86 to 47, median frequency from 10.2 to 3.4, spectral edge from 23.5 to 16.7 (all P<.05). During naloxone infusion, the median percent increase in sympathetic heart rate variability was 487% (P<.05), median frequency increased 163% (P<.05), bispectral index (10%), and spectral edge (7%) did not significantly change. The increase in median frequency was delayed compared to sympathetic heart rate variability and median frequency remained elevated after sympathetic heart rate variability returned to anesthetized baseline in 5 of 8 cases. Our results show that median frequency and sympathetic heart rate variability increase during opioid detoxification, but the time course of each response is different. Median frequency is a more sensitive electroencephalogram indicator of opioid reversal than bispectral index or spectral edge.

Anesthesia, Intravenous↗

CYP2E1 is not involved in early alcohol-induced liver injury.

The continuous intragastric enteral feeding protocol in the rat was a major development in alcohol-induced liver injury (ALI) research. Much of what has been learned to date involves inhibitors or nutritional manipulations that may not be specific. Knockout technology avoids these potential problems. Therefore, we used long-term intragastric cannulation in mice to study early ALI. Reactive oxygen species are involved in mechanisms of early ALI; however, their key source remains unclear. Cytochrome P-450 (CYP)2E1 is induced predominantly in hepatocytes by ethanol and could be one source of reactive oxygen species leading to liver injury. We aimed to determine if CYP2E1 was involved in ALI by adapting the enteral alcohol (EA) feeding model to CYP2E1 knockout (-/-) mice. Female CYP2E1 wild-type (+/+) or -/- mice were given a high-fat liquid diet with either ethanol or isocaloric maltose-dextrin as control continuously for 4 wk. All mice gained weight steadily over 4 wk, and there were no significant differences between groups. There were also no differences in ethanol elimination rates between CYP2E1 +/+ and -/- mice after acute ethanol administration to naive mice or mice receiving EA for 4 wk. However, EA stimulated rates 1.4-fold in both groups. EA elevated serum aspartate aminotransferase levels threefold to similar levels over control in both CYP2E1 +/+ and -/- mice. Liver histology was normal in control groups. In contrast, mice given ethanol developed mild steatosis, slight inflammation, and necrosis; however, there were no differences between the CYP2E1 +/+ and -/- groups. Chronic EA induced other CYP families (CYP3A, CYP2A12, CYP1A, and CYP2B) to the same extent in CYP2E1 +/+ and -/- mice. Furthermore, POBN radical adducts were also similar in both groups. Data presented here are consistent with the hypothesis that oxidants from CYP2E1 play only a small role in mechanisms of early ALI in mice. Moreover, this new mouse model illustrates the utility of knockout technology in ALI research.

Animals↗

Identification and cloning of an orphan G protein-coupled receptor of the glycoprotein hormone receptor subfamily.

Mining of the EST database identified a human EST that was predicted to encode a novel member of the glycoprotein hormone receptor subfamily. Based on the sequence information, the full-length coding region of this gene was isolated and sequenced. This gene, designated HG38, is predicted to encode a polypeptide of 907 amino acid residues with a putative signal peptide sequence at its very N-terminus. HG38 is most closely related to members of the glycoprotein hormone receptor subfamily with approximately 35% overall identity at the protein sequence level. As with the glycoprotein hormone receptors, HG38 contains a long extracellular domain with a total of 16 leucine-rich repeats. Northern blot analysis showed that HG38 was expressed in skeletal muscle, placenta, spinal cord, and various regions of the brain. Radiation hybrid mapping placed HG38 into human chromosome 12q22-23. HG38 is most likely to be a receptor for a novel class of glycoprotein ligands.

Amino Acid Sequence↗

Ultra-rapid opioid detoxification increases spontaneous ventilation.

STUDY OBJECTIVE: To evaluate the effect of ultra-rapid opioid detoxification on spontaneous respiration. DESIGN: Prospective study. SETTING: University of Illinois, Chicago, Hospital. PATIENTS: 20 ASA physical status I and II patients undergoing ultra-rapid opioid detoxification, and 5 ASA physical status I and II control patients undergoing surgical procedures. INTERVENTIONS: Ultra-rapid opioid detoxification patients were anesthetized with propofol, intubated, and spontaneously ventilating. Opioid detoxification was achieved by giving repeated increasing intragastric doses of naltrexone. Control patients were anesthetized with propofol and 70% nitrous oxide and were time-based controls for opioid detoxification. MEASUREMENTS AND MAIN RESULTS: Respiratory rate and minute ventilation were measured and increased 80% to 100% during opioid detoxification (p < 0.05). Respiratory rate and minute ventilation did not change in controls. Oxygen consumption and carbon dioxide (CO2) production were measured in separate studies and increased during ultra-rapid opioid detoxification with increases in spontaneous ventilation, but not when the patients were paralyzed. CONCLUSIONS: Spontaneous ventilation increases during opioid detoxification without a change in end-tidal CO2. An increase in metabolism is produced in opioid withdrawal that is mediated by elevated muscle activity.

Anesthetics, Inhalation↗

Simultaneous increases in respiration and sympathetic function during opiate detoxification.

This study evaluated the relationship between the sympathetic withdrawal response and increases in spontaneous ventilation during naltrexone treatment in opioid-dependent patients. Naltrexone was given in repeated increasing doses by orogastric tube to 16 opioid-dependent patients during propofol anesthesia. Sympathetic activity was evaluated in 64-second segments by low frequency heart rate variability (0.02-0.10 Hz) and minute ventilation was measured every 15 minutes. During naltrexone treatment, heart rate and blood pressure increased with no change in the electroencephalogram as measured by the bispectral index. Sympathetic activity increased five-fold and minute ventilation increased by 50% during naltrexone administration. There was a significant correlation between the time of the peak sympathetic response and peak ventilation (r = 0.83, p < 0.001). In three control patients, who received anesthesia for surgery without naltrexone treatment, no increases in sympathetic or respiratory parameters were seen. These results indicate that peak sympathetic and respiratory stimulation occur together during opiate receptor antagonism in opioid addicts.

Adult↗

Comparison of the effects of AV nodal ablation versus AV nodal modification in patients with congestive heart failure and uncontrolled atrial fibrillation.

Radiofrequency (RF) catheter ablation of the atrioventricular node (AVN) and implantation of a ventricular pacemaker can improve cardiac performance in patients with congestive heart failure (CHF) and uncontrolled atrial fibrillation (AF). Alternatively, RF catheter modification of the AVN has been proposed to slow ventricular response during AF without requirement for permanent pacing. Among 44 consecutive patients (mean age 69.7 +/- 10.2 years) with drug resistant chronic AF, 22 (group I) had AVN ablation with permanent ventricular pacemaker implantation, while 22 patients had attempted AVN modification. Complete AV block was obtained in all group I patients while only seven (32%) AVN modification patients (group II) had permanent slowing of ventricular rate. Among patients in group I, mean left ventricular ejection fraction (EF) increased from 32.2% +/- 8.8% before ablation to 41.9% +/- 14.6% 4-weeks postablation (P < 0.01); exercise tolerance time (ETT) increased from 2.9 +/- 2.2 minutes to 4.5 +/- 2.9 minutes (P < 0.01); and quality-of-life score decreased from 66.1 +/- 22.6 to 36.9 +/- 17.1 (P < 0.01). By comparison, there was only a small increase in ETT in the seven successful group II patients (2.4 +/- 1.8 minutes to 3.0 +/- 1.9 minutes; P < 0.05) and there was no significant change in EF or quality-of-life. While AVN ablation can occasionally have transient adverse effects, it is more effective than AVN modification for improving cardiac performance in selected patients with CHF and AF.

Aged↗

The electronic patient record in general practice--a South-African perspective.

A research project was undertaken to design an electronic medical record system which will cater for the specific needs of South African general practitioners and their unique requirements. The project was launched by sending out a questionnaire to general practitioners in the Free State, trying to determine their specific requirements and to gain insight into their attitudes and opinions regarding the use of computers, especially the computer-based patient record, in a general practice setting. The results indicated that there was a need to replace the current manual patient record with an electronic version, and that the attitudes of the general practitioners in South Africa were generally favourable regarding implementing and using such a system. Given these results, we can proceed to design a computer-based patient record system, specifically addressing the needs and requirements of the South African general practitioner.

Attitude to Computers↗

A comparison of a manual and a computer system in a primary health care clinic.

Previous research has shown that nurses providing primary health care in local clinics are burdened with extensive administrative duties. These administrative tasks are so time consuming that less time can be devoted to direct patient care, their primary function. Certain assertions have been made with regard to computerising the total environment of patient records, capturing statistical indicators, stock control, etc. It is said that computerising the clinic at the point of service will naturally lead to less time devoted to administrative tasks, thus increasing the time available for direct patient care. This study was done to determine whether this assertion is true. It was conducted by means of a combined quantitative and qualitative research design. The manual system and a computer system were quantitatively compared by means of various time measurements. The perceptions of patients and staff regarding computers were explored qualitatively by means of questionnaires. It was found that computerising the nurse's consulting room does not enhance the ratio between the time devoted to administrative tasks and the time devoted to patient care. In fact, the consultation time was longer with the computerised system than with the manual system. Some limiting factors in the computerisation process were discovered, the most important of which were the lack of computer literacy and typing skills of the nursing staff.

Ambulatory Care↗

Keeping your balance.

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Adaptation, Psychological↗

Less is more.

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Adaptation, Psychological↗

Hospital costs and severity of illness in three types of elective surgery.

BACKGROUND: If patients who are more severely ill have greater hospital costs for surgery, then health-care reimbursements need to be adjusted appropriately so that providers caring for more seriously ill patients are not penalized for incurring higher costs. The authors' goal for this study was to determine if severity of illness, as measured by either the American Society of Anesthesiologists Physical Status (ASA PS) or the comorbidity index developed by Charlson, can predict anesthesia costs, operating room costs, total hospital costs, or length of stay for elective surgery. METHODS: The authors randomly selected 224 inpatients (60% sampling fraction) having either colectomy (n = 30), total knee replacement (n = 100), or laparoscopic cholecystectomy (n = 94) from September 1993 to September 1994. For each surgical procedure, backward-elimination multiple regression was used to build models to predict (1) total hospital costs, (2) operating room costs, (3) anesthesia costs, and (4) length of stay. Explanatory candidate variables included patient age (years), sex, ASA PS, Charlson comorbidity index (which weighs the number and seriousness of coexisting diseases), and type of insurance (Medicare/Medicaid, managed care, or indemnity). These analyses were repeated for the pooled data of all 224 patients. Costs (not patient charges) were obtained from the hospital cost accounting software. RESULTS: Mean total hospital costs were $3,778 (95% confidence interval +/- 299) for laparoscopic cholecystectomy, $13,614 (95% CI +/- 3,019) for colectomy, and $18,788 (95% CI +/- 573) for knee replacement. The correlation (r) between ASA PS and Charlson comorbidity scores equaled 0.34 (P < .001). No consistent relation was found between hospital costs and either of the two severity-of-illness indices. The Charlson comorbidity index (but not the ASA PS) predicted hospital costs only for knee replacement (P = .003). The ASA PS, but not the Charlson index, predicted operating room and anesthesia costs only for colectomy (P < .03). CONCLUSIONS: Severity of illness, as categorized by ASA PS categories 1-3 or by the Charlson comorbidity index, was not a consistent predictor of hospital costs and lengths of stay for three types of elective surgery. Hospital resources for these lower-risk elective procedures may be expended primarily to manage the consequences of the surgical disease, rather than to manage the patient's coexisting diseases.

Aged↗