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Biomedical subjects

William D White

Publications and source records attributed to William D White.

At least 19 recordsLinked to original sources
PubMed2005

Genetic polymorphisms and the risk of stroke after cardiac surgery.

BACKGROUND AND PURPOSE: Stroke represents a significant cause of morbidity and mortality after cardiac surgery. Although the risk of stroke varies according to both patient and procedural factors, the impact of genetic variants on stroke risk is not well understood. Therefore, we tested the hypothesis that specific genetic polymorphisms are associated with an increased risk of stroke after cardiac surgery. METHODS: Patients undergoing cardiac surgery utilizing cardiopulmonary bypass surgery were studied. DNA was isolated from preoperative blood and analyzed for 26 different single-nucleotide polymorphisms. Multivariable logistic regression modeling was used to determine the association of clinical and genetic characteristics with stroke. Permutation analysis was used to adjust for multiple comparisons inherent in genetic association studies. RESULTS: A total of 1635 patients experiencing 28 strokes (1.7%) were included in the final genetic model. The combination of the 2 minor alleles of C-reactive protein (CRP; 3'UTR 1846C/T) and interleukin-6 (IL-6; -174G/C) polymorphisms, occurring in 583 (35.7%) patients, was significantly associated with stroke (odds ratio, 3.3; 95% CI, 1.4 to 8.1; P=0.0023). In a multivariable logistic model adjusting for age, the CRP and IL-6 single-nucleotide polymorphism combination remained significantly associated with stroke (P=0.0020). CONCLUSIONS: We demonstrate that common genetic variants of CRP (3'UTR 1846C/T) and IL-6 (-174G/C) are significantly associated with the risk of stroke after cardiac surgery, suggesting a pivotal role of inflammation in post-cardiac surgery stroke.

Aged↗
PubMed2005

Cerebral physiology of cardiac surgical patients treated with the perfluorocarbon emulsion, AF0144.

BACKGROUND: Perfluorooctyl bromide is a biologically inert compound with short biologic retention and high oxygen solubility. The purpose of this study was to assess the effect of the perfluorocarbon emulsion, AF0144 (Perflubron, Alliance Pharmaceutical Corp, San Diego, CA), used in conjunction with acute normovolemic hemodilution on cerebral blood flow and cerebral emboli measurements during coronary artery bypass grafting with cardiopulmonary bypass. METHODS: Thirty-six adult cardiac surgical patients were enrolled in a single-institution, randomized, controlled, single-blind dose escalation trial. Autologous whole blood was harvested from each patient to target an on-bypass hematocrit of 20% to 22%. Placebo, low dose (1.8 g/kg) or high dose (2.7 g/kg) AF0144 was administered. Transcranial Doppler ultrasonography was used to quantitate cerebral emboli and xenon-133 clearance was used to measure cerebral blood flow. RESULTS: Cerebral blood flow was increased in both AF0144-treated groups compared with placebo (p = 0.006, low dose vs control; p = 0.036, high dose vs control). Numbers of cerebral emboli were greater in the high-dose AF0144-treated group versus control during the time periods from aortic cannulation through aortic cross-clamp placement (p = 0.026) and from aortic cross-clamp placement through cross-clamp removal (p = 0.008). CONCLUSIONS: The perfluorocarbon emulsion, AF0144, increased cerebral blood flow during cardiopulmonary bypass. In addition, total cerebral emboli load during bypass was greater in patients receiving high-dose AF0144.

Adult↗
PubMed2005

General anesthesia improves fetal cerebral oxygenation without evidence of subsequent neuronal injury.

Anesthetic exposure during pregnancy is viewed as a relatively routine medical practice. However, recent rodent studies have suggested that common anesthetic agents can damage the developing brain. Here we assessed this claim in a higher order species by exposing previously instrumented near-term pregnant sheep at gestational day 122 (+/-1) to a combination of midazolam, sodium thiopental, and isoflurane at clinically relevant doses and means of anesthetic delivery (i.e., active ventilation). Four hours of maternal general anesthesia produced an initial increase in fetal systemic oxygenation and a sustained increase in fetal cerebral oxygenation, as determined by in utero near-infrared spectroscopy. Postexposure monitoring failed to identify changes in physiologic status that could be injurious to the fetal brain. Finally, through the histologic assessment of noninstrumented sheep at the same gestational time point, we found no evidence for a direct fetal neuro-toxic effect of our triple-drug regimen. Collectively, these results appear to corroborate the presumed safety of inhalational anesthetic use during pregnancy.

Anesthesia, General↗
PubMed2005

Preoperative statin therapy does not reduce cognitive dysfunction after cardiopulmonary bypass.

OBJECTIVE: The purpose of this study was to determine if patients receiving statin therapy before coronary artery bypass grafting surgery would have less cognitive dysfunction after cardiopulmonary bypass as a consequence of a diminished inflammatory response. DESIGN: Retrospective observational study of patients undergoing coronary artery bypass grafting surgery. SETTING: Referral center for cardiothoracic surgery at a university hospital. PARTICIPANTS: Four hundred forty patients undergoing coronary artery bypass grafting surgery with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-five percent of patients received statins in the preoperative period. Multivariable analysis revealed no effect of preoperative statin therapy on cognitive function (p = 0.67). Post hoc analysis revealed that statin therapy at hospital discharge was associated with less improvement in cognitive performance at 6 weeks after surgery (p = 0.011). No significant differences were found between statin therapy groups in either range or maximum value of any of the cytokines (p > 0.05). CONCLUSIONS: Preoperative statin therapy did not decrease the inflammatory response to cardiopulmonary bypass or the cognitive dysfunction commonly seen after cardiac surgery.

C-Reactive Protein↗
PubMed2005

A randomized, open-label pilot comparison of gabapentin and bupropion SR for smoking cessation.

This 6-week, randomized, open-label pilot study estimated the treatment effect size of gabapentin (n = 17) compared with bupropion SR (n = 19) for smoking cessation, thereby allowing sample size calculations for a definitive comparison study. The primary outcome measure was smoking cessation. Secondary outcome measures included smoking reduction and withdrawal severity. Gabapentin was less efficacious than bupropion for smoking cessation but was associated with fewer dropouts from adverse effects. Withdrawal severity was less with bupropion. Bupropion remains the first-line non-nicotine pharmacotherapy for smoking cessation. Further study is required to determine if gabapentin has any useful role in smoking cessation. Based on our primary outcome measure, 79 subjects would be required in each treatment group of a two-armed study to achieve 90% power for detecting a difference in efficacy between gabapentin and bupropion.

Adolescent↗
PubMed2005

Intrathecal morphine for analgesia after postpartum bilateral tubal ligation.

Postpartum bilateral tubal ligation (PPBTL) causes postoperative pain. We designed this study to determine the efficacy of 50 microg intrathecal morphine for analgesia after PPBTL. Sixty-five women received spinal anesthesia with 12.75 mg hyperbaric bupivacaine, 20 microg of fentanyl, and either 50 microg of morphine (morphine group) or 0.05 mL of saline (control group). Postoperative analgesia was provided with regular naproxen 500 mg and oxycodone 5 mg/acetaminophen 325 mg mixture as needed. Overall, satisfaction was higher (P=0.003) and pain was less intense at rest (P=0.008) and on movement (P <0.0001) in the morphine group. There was no significant overall difference in nausea, pruritus, or sedation scores, but vomiting occurred more frequently in the morphine group (21.4% versus 3.5%; P=0.052). In post hoc comparisons, pain at rest within the morphine group was significantly less at 4 h (P=0.006), pain on movement was significantly less at 4 h (P=0.002) and 12 h (P=0.0004), and pruritus was significantly more frequent at 12 h (P=0.002) compared with the control group. Oxycodone 5 mg/acetaminophen 325 mg mixture consumption was significantly smaller (P=0.006) and the time to first request of analgesia was significantly longer (P=0.006) in the morphine group. We conclude that the addition of 50 microg of morphine to intrathecal hyperbaric bupivacaine and fentanyl provides improved postoperative analgesia in women undergoing PPBTL.

Adult↗
PubMed2005

Preincisional dextromethorphan combined with thoracic epidural anesthesia and analgesia improves postoperative pain and bowel function in patients undergoing colonic surgery.

Colonic surgery is associated with severe postoperative pain and postoperative ileus, which contribute to delayed hospital discharge. In previous studies, we demonstrated that IM dextromethorphan (DM) provided preemptive analgesia and improved postoperative pain. The benefit of thoracic epidural anesthesia (TEA) and postoperative epidural analgesia on postoperative pain was well demonstrated. The goal of this study was to investigate the effect of preincisional IM DM combined with intraoperative TEA and postoperative patient-controlled epidural analgesia (PCEA) on pain and bowel function after colonic surgery. Patients were randomized into 3 equal groups to receive: 1) chlorpheniramine maleate (CPM) 20 mg and general anesthesia (CPM-GA); 2) CPM 20 mg and GA combined with TEA (CPM-TEA); or 3) DM 40 mg (containing 20 mg of CPM) and GA combined with TEA (DM-TEA). The CPM, DM, and TEA with lidocaine were administered after GA induction via an IM injection and 30 min before the skin incision. All patients received postoperative PCEA for pain control. Analgesic effects were evaluated for 72 h after surgery using visual analog scale pain scores at rest and moving, time to first PCEA request for pain relief, total PCEA consumption, and the time to first passage of flatus. Statistically significant improvement of postoperative pain and bowel function was observed in the following order: DM-TEA > CPM-TEA > CPM-GA. Compared with the CPM-TEA group, the DM-TEA group averaged 1.6 points lower on first-hour pain scores, 40 min longer to first PCEA request, 15.8 mL less PCEA drug over 72 h, and 14.7 h earlier bowel function (all P < 0.01). We conclude that the combination of preincisional DM (40 mg IM), intraoperative TEA, and postoperative PCEA enhances analgesia and facilitates recovery of bowel function, suggesting possible synergistic interaction with local anesthetics and opioids.

Adolescent↗
PubMed2005

Renal artery stenosis is not associated with the development of acute renal failure following coronary artery bypass grafting.

BACKGROUND: Acute renal failure (ARF) is a frequent complication of coronary artery bypass grafting (CABG) surgery and is strongly associated with perioperative morbidity and mortality. We hypothesized that renal artery stenosis (RAS), causing occult renal ischemia, may be an important factor contributing to development of ARF after CABG surgery. METHODS: Preoperative and intraoperative data on 798 consecutive adult patients undergoing CABG surgery with cardiopulmonary bypass from February 1, 1995 to February 1, 1997 (who had also undergone an abdominal aortogram for the evaluation of RAS) were recorded and entered into a computerized database. The development of ARF was defined as a rise in serum creatinine of 1 mg/dL (88.4 micromol/L) above baseline postoperatively. The association between the presence of renal artery stenosis together with preoperative and intraoperative variables and the development of ARF was assessed by multivariate logistic regression. RESULTS: A total of 798 patients underwent isolated coronary bypass grafting, of which 18.7% demonstrated 50% or more RAS. ARF developed in 82 patients (10.2%), of which three (0.3%) required dialysis support. The mortality for patients who developed ARF was 14% (OR 15, P=0.0001) compared to 0.2% among those who did not develop ARF. The presence of renal artery stenosis of any severity ranging from unilateral 50% RAS to bilateral 95% RAS was not associated with the subsequent development of ARF. CONCLUSIONS: The development of ARF following CABG surgery is associated with high mortality. The presence of RAS does not appear to increase the risk for developing ARF.

Acute Kidney Injury↗
PubMed2004

Preliminary report of the effects of complement suppression with pexelizumab on neurocognitive decline after coronary artery bypass graft surgery.

BACKGROUND AND PURPOSE: Pharmacological modulation of complement activation recently has been postulated as a therapeutic target in the treatment of neurological injury. We hypothesized that pexelizumab, a humanized scFv monoclonal antibody directed against the C5 complement component, would limit deficits in patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass. METHODS: The Phase II Pexelizumab study was a 914-patient, double-blind, placebo-controlled, 65-center study of patients undergoing coronary artery bypass graft surgery. Patients were randomized to pexelizumab bolus, bolus plus infusion, or placebo. Neurological and neurocognitive functions were assessed as secondary endpoints at baseline and on postoperative days (POD) 4 and 30. Cognitive deficits were assessed with multivariable tests accounting for baseline cognition, age, diabetes, years of education, sex, elevated creatinine, history of myocardial infarction, neurological disorder or congestive heart failure, and cardiopulmonary bypass time. RESULTS: Pexelizumab had no statistically significant effect on the primary composite endpoint or on overall cognition. When domain specific effects were examined, a decline of at least 10% in the visuo-spatial domain was observed on POD 4 in 56% of patients receiving placebo compared with 40% receiving pexelizumab by bolus and infusion (P=0.003). Similarly, on POD 30, a 10% decline was present in 21% of patients in the placebo group versus only 12% of the drug bolus plus infusion group (P=0.016). No differences were seen between treatment groups in any of the other domains. CONCLUSIONS: Pexelizumab administration for 24 hours perioperatively had no effect on global measures of cognition but may reduce dysfunction in the visuo-spatial domain.

Aged↗
PubMed2004

Transcranial Doppler emboli count predicts rise in creatinine after coronary artery bypass graft surgery.

OBJECTIVE: To examine the correlation between transcranial Doppler ultrasonography-detected emboli during coronary artery bypass graft surgery with cardiopulmonary bypass and renal dysfunction as determined by the postoperative change in creatinine. DESIGN: Retrospective review of data from the anesthesia and cardiothoracic surgery databases. SETTING: Tertiary care university hospital. PARTICIPANTS: Two hundred eighty-six patients undergoing coronary artery bypass graft surgery. INTERVENTIONS: Transcranial Doppler ultrasonography of the right middle cerebral artery was performed after induction of general anesthesia through completion of the operation. Doppler signals were recorded and emboli counts determined using an automated counting system. MEASUREMENTS AND MAIN RESULTS: Renal dysfunction was assessed as the change in creatinine from the preoperative value to the maximum postoperative value (Delta-Cr). There was a significant (p = 0.0003) univariate correlation between postoperative change in creatinine and total number of Doppler-detected emboli. The effect of total number of emboli remained significant (p = 0.0038) in the multivariable analysis after adjustment for covariables (age, sex, number of grafts, left ventricular ejection fraction, hypertension, history of congestive heart failure, diabetes, cardiopulmonary bypass time, preoperative creatinine, and maximum postoperative creatinine). CONCLUSIONS: Increased numbers of Doppler-detected emboli during coronary artery bypass graft surgery are associated with postoperative renal dysfunction.

Anesthesia, General↗
PubMed2004

Maternal insufflation during the second trimester equivalent produces hypercapnia, acidosis, and prolonged hypoxia in fetal sheep.

BACKGROUND: Anecdotal reports suggest that the second trimester is the safest time to conduct a laparoscopic procedure on a pregnant patient, but this supposition has not been tested empirically. METHODS: Previously instrumented preterm sheep (total n = 8) at gestational day 90 (term, 145 days) were anesthetized and then insufflated with carbon dioxide for 60 min at a pressure of 15 mmHg. Cardiovascular parameters were continuously recorded while blood gas status was determined before and at 15-min intervals during and up to 2 h after insufflation. RESULTS: Insufflation produced minimal maternal blood gas or cardiovascular changes except for a significant reduction in uterine blood flow. The decrease in perfusion increased fetal arterial blood partial pressure of carbon dioxide and decreased fetal pH, oxygen saturation, and oxygen content; there was also progressive fetal hypotension and bradycardia. After manually deflating the ewe, uterine blood flow returned to normal, and the fetal partial pressure of carbon dioxide and pH changes resolved within 1 h. However, fetal oxygen saturation and content remained depressed, and fetal cardiovascular status continued to decline during the 2-h postinsufflation monitoring period. CONCLUSION: Previous studies with near-term sheep determined that carbon dioxide pneumoperitoneum produces respiratory acidosis but does not decrease fetal oxygenation. In contrast, the current findings indicate that in the preterm fetus, insufflation-induced hypercapnia and acidosis are accompanied by prolonged fetal hypoxia and cardiovascular depression. This result suggests that additional work should be conducted to confirm the presumed safety of conducting minimally invasive procedures during the second trimester.

Acidosis↗
PubMed2004

The impact of managed care on substance abuse treatment services.

OBJECTIVE: To examine the impact of managed care on the number and types of services offered by substance abuse treatment (SAT) facilities. Both the number and types of services offered are important factors to analyze, as research shows that a broad range of services increases treatment effectiveness. DATA SOURCES: The 2000 National Survey of Substance Abuse Treatment Services (NSSATS), which is designed to collect data on service offerings and other characteristics of SAT facilities in the United States. These data are merged with data from the 2002 Area Resource File (ARF), a county-specific database containing information on population and managed care activity. We use data on 10,513 facilities, virtually a census of all SAT facilities. STUDY DESIGN: We estimate the impact of managed care (MC) on the number and types of services offered by SAT facilities using instrumental variables (IV) techniques that account for possible endogeneity between facilities' involvement in MC and service offerings. Due to limitations of the NSSATS data, MC and specific services are modeled as binary variables. PRINCIPAL FINDINGS: We find that managed care causes SAT facilities to offer, on average, approximately two fewer services. This effect is concentrated primarily in medical testing services (i.e., tests for TB, HIV/AIDs, and STDs). We also find that MC increases the likelihood of offering substance abuse assessment and relapse prevention groups, but decreases the likelihood of offering outcome follow-up. CONCLUSION: Our findings raise policy concerns that managed care may reduce treatment effectiveness by limiting the range of services offered to meet patient needs. Further, reduced onsite medical testing may contribute to the spread of infectious diseases that pose important public health concerns.

AIDS Serodiagnosis↗
PubMed2004

A randomized comparison of a multimodal management strategy versus combination antiemetics for the prevention of postoperative nausea and vomiting.

A multimodal management strategy for the prevention of postoperative nausea and vomiting (PONV) appears to be superior to single-drug prophylaxis. We tested the hypothesis that a multimodal PONV prophylaxis regimen incorporating total IV anesthesia (TIVA) with propofol and a combination of ondansetron and droperidol is more effective than a combination of these antiemetics in the presence of an inhaled anesthetic. Ninety patients undergoing laparoscopic cholecystectomy were randomized to one of three groups. Group 1 (multimodal group) received TIVA with propofol, droperidol, and ondansetron. Group 2 (combination group) received droperidol and ondansetron with isoflurane and nitrous oxide for the maintenance of anesthesia. Group 3 (TIVA group) received propofol for the induction and maintenance of anesthesia. The complete response rate (no PONV and no rescue antiemetic) at 2 h after surgery was 90%, 63%, and 66% in Groups 1, 2, and 3, respectively (P < 0.05, Group 1 versus Group 2). At 24 h, the complete response rate was 80%, 63%, and 43% in Groups 1, 2, and 3, respectively (P < 0.05, Group 1 versus Group 3). Patient satisfaction was also greater in the multimodal group than in the other two groups in the postanesthesia care unit (P < 0.05). In conclusion, the multimodal management strategy for PONV was associated with a higher complete response rate and greater patient satisfaction when compared with similar antiemetic prophylaxis with inhaled anesthesia or TIVA with propofol.

Adult↗
PubMed2003

Novel diagnostic test for acute stroke.

BACKGROUND AND PURPOSE: The absence of a widely available and sensitive diagnostic test for acute cerebral ischemia remains a significant limitation in the diagnosis and management of stroke. The objective of this study was to examine the feasibility of developing a diagnostic panel of blood-borne biochemical markers of cerebral ischemia. METHODS: Serial blood samples were obtained from patients (n=65 with suspected ischemic stroke, n=157 control subjects) presenting to an academic medical center emergency department. We analyzed 26 blood-borne markers believed to play a role in the ischemic cascade and created a 3-variable logistic regression model to predict the clinical diagnosis of stroke, defined as persistent neurological symptoms of cerebral ischemia lasting >24 hours. RESULTS: Of the 26 blood-borne markers analyzed, univariate logistic analysis revealed that 4 were highly correlated with stroke (P<0.001): a marker of glial activation (S100beta), 2 markers of inflammation (matrix metalloproteinase-9 and vascular cell adhesion molecule), and 1 marker of thrombosis (von Willebrand factor). When the outcome level was set to a cutoff of P=0.1, our logistic model provided a sensitivity and specificity of 90% for predicting stroke. CONCLUSIONS: A panel of blood-borne biochemical markers may be helpful in identifying patients with acute cerebral ischemia who could benefit from urgent care. Such a test may also be helpful in identifying stroke patients in the prehospital setting so that they could be fast-tracked to an institution equipped to care for patients with acute stroke.

Acute Disease↗
PubMed2003

Effects of positive-pressure ventilation, pericardial effusion, and cardiac tamponade on respiratory variation in transmitral flow velocities.

OBJECTIVE: To determine the effects of positive-pressure ventilation and experimentally induced pericardial effusion and tamponade on transmitral flow velocities in dogs. DESIGN: Descriptive. SETTING: University laboratory. PARTICIPANTS: Eleven tracheally intubated and mechanically ventilated dogs. INTERVENTIONS: Experimental pericardial effusion and cardiac tamponade were created by pericardial injection of warm saline. MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters and pericardial pressures were monitored in the 11 dogs. Pulsed-wave Doppler tracings of mitral valve flow were obtained at the leaflet tips along with hemodynamic measurements at 4 stages: control, effusion (no decrease in mean arterial pressure), tamponade (>or=40% decrease in mean arterial pressure), and tamponade relief (after evacuation of pericardial fluid). Maximal variation (36%) in transmitral flow velocity over the respiratory cycle during positive-pressure ventilation was seen in the control stage. In the effusion and tamponade stages, variation in transmitral flow velocity decreased progressively to 29% (p = 0.1804, not significant) and 16% (p < 0.0001), respectively. CONCLUSION: Intrathoracic pressure and lung volume changes caused by positive-pressure ventilation influence transmitral flow velocity patterns. Respiratory variation in transvalvular flow is pronounced during standard positive-pressure mechanical ventilation, decreases in the presence of pericardial effusion, and becomes almost nonexistent when cardiac tamponade is present. These findings show that the echocardiographic criteria used to diagnose cardiac tamponade based on mitral valve inflow patterns are different during positive-pressure ventilation from spontaneously breathing subjects.

Animals↗
PubMed2003

Psychogenic coma: case report.

Coma is present when the patient appears asleep, is unrousable, and unresponsive. Where no underlying medical condition is found, the role of the psychiatrist may become prominent. We present a clinical case and review the literature on psychogenic coma. According to DSM-IV-TR, psychogenic coma is a dissociative disorder not otherwise specified. Management is largely supportive. Principles include speaking in a reassuring manner and avoiding repeated painful stimuli. Education of family and other professionals that symptoms are real and not consciously feigned may be important. There may be a short-term role for anxiolytic and/or antipsychotic medication to assist return to consciousness.

Adult↗
PubMed2003

Learning needs of patients with vasovagal syncope.

This exploratory, descriptive study was undertaken to identify common questions and concerns that patients with vasovagal syncope have about their condition. A semistructured interview format was used to survey patients' subjective learning needs. Interview transcripts were analyzed qualitatively for content themes using the grounded theory procedure of open coding. A convenience sample of 10 patients referred to a university-based syncope clinic at a tertiary care centre for investigation of unexplained syncope was used. The diagnosis of vasovagal syncope was confirmed based on clinical features and tilt table testing. Patients universally communicated broad areas of learning needs with regard to their condition, including etiology, management, natural history, and prognosis. A number of more specific subcategories of learning needs were also found in the majority of patients sampled. Patients with vasovagal syncope share a number of well-defined categories of subjectively identified learning needs. These categories should guide attempts to provide patients with relevant counselling, reassurance, and education.

Adult↗