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Biomedical subjects

W D Watkins

Publications and source records attributed to W D Watkins.

At least 19 recordsLinked to original sources
PubMed2000

Diclofenac sodium (Voltaren) reduced exercise-induced injury in human skeletal muscle.

PURPOSE: To examine the effects of prolonged systemic administration of diclofenac sodium (Voltaren), a nonsteroidal anti-inflammatory drug, on objective indices of exercise-induced muscle damage in humans. METHODS: Fifty-four volunteers (mean age, 26.4 yr; range, 18-35) participated in this randomized double-blind, placebo-controlled trial. To achieve steady-state tissue levels, either placebo or diclofenac was orally administered two times a day for 27 consecutive days. A strenuous 20-min stepping exercise program, about which the subjects were unfamiliar, was conducted on day 15. Creatine kinase (CK) activities were measured immediately before the exercise session and on days 16, 18, and 27. Vastus lateralis muscle samples were obtained immediately before exercise and on day 27 for subsequent histological characterization of muscle inflammation. RESULTS: The preexercise muscle samples revealed no difference in muscle damage between the two groups. However, the postexercise muscle samples showed that the diclofenac-treated group demonstrated less muscle tissue damage than placebo-treated subjects (P = 0.002). The administration of diclofenac also resulted in a significant lowering of post-/pre-exercise CK ratios on days 18 (P = 0.03) and 27 (P = 0.02) compared with the placebo group, an indirect finding that supports the possibility of diclofenac reducing exercise-induced muscle damage. CONCLUSION: These findings demonstrate preadministration of diclofenac (in accordance with tissue half-life pharmacokinetics) significantly reduces quantitative indices of exercise-induced skeletal muscle damage in human muscle.

Administration, Oral↗
PubMed1998

Superoxide-induced changes in endothelin (ET) receptors in hepatic stellate cells.

BACKGROUND/AIMS: Reactive oxygen species are mediators of various pathophysiologic events, including postischemic reperfusion injury and inflammation. Generation of reactive oxygen species and consequent organ injury are associated with increased levels of a powerful vasoconstrictor peptide endothelin-1. Current evidence suggests that actions of endothelin-1 on the contractile and fibrogenic transdifferentiated stellate cells may play a critical role in hepatic pathophysiology. The aim of this investigation was to determine whether reactive oxygen species modulate the synthesis of endothelin-1 and its receptors in stellate cells. METHODS: Primary cultures of transdifferentiated stellate cells were exposed to reactive oxygen species-generating system, hypoxanthine/xanthine oxidase, before determination of endothelin-1 and its receptors. RESULTS: The treatment caused an initial decrease in ET-1 receptor density (about 30% at 30 min), followed by a significant increase over the basal level at 6 h. The increase in the receptors, which occurred specifically in the ET(B) subtype, progressed thereafter up to 24 h and was accompanied by an augmented functional response, as indicated by an enhanced endothelin-1-induced release of [3H]arachidonic acid from the prelabeled cells. Furthermore, treatment of cells for 24 h but not 30 min caused increased expression of ET(B) mRNA as determined by semi-quantitative polymerase chain reaction. The release of endothelin-1 in the culture medium was also enhanced by hypoxanthine/xanthine oxidase treatment. These effects of hypoxanthine/xanthine oxidase were inhibited by superoxide dismutase and dimethyl sulfoxide. ET-1-induced [3H]arachidonic acid release was also inhibited by the ET(B) receptor antagonist BQ788, but not by the ET(A) receptor antagonist BQ123. CONCLUSIONS: These findings indicate that interactions between ET-1 and stellate cells during episodes of the generation of reactive oxygen species can be an important mechanism in the pathophysiology of hepatic disorders.

Adipocytes↗
PubMed1998

Benchmarking the perioperative process: II. Introducing anesthesia clinical pathways to improve processes and outcomes and to reduce nursing labor intensity in ambulatory orthopedic surgery.

STUDY OBJECTIVES: (1) To introduce anesthesia clinical pathways as a management tool to improve the quality of care; (2) to use the Procedural Times Glossary published by the Association of Anesthesia Clinical Directors (AACD) as a template for data collection and analysis; and (3) to determine the effects of anesthesia clinical pathways on surgical processes, outcomes, and costs in common ambulatory orthopedic surgery. DESIGN: Hospital database and patient chart review of consecutive patients undergoing anterior cruciate ligament reconstruction (ACLR) during academic years (AY) 1995-1996 and 1996-1997. Patient data from AY 1995-1996, during which no intraoperative anesthesia clinical pathways existed, served as historical controls. Data from AY 1996-1997, during which intraoperative anesthesia clinical pathways were used, served as the treatment group. Regional anesthesia options were routinely offered to patients in the clinical pathway. SETTING: Ambulatory surgery center in a teaching hospital. MEASUREMENTS AND MAIN RESULTS: The records of 503 ASA physical status I and II patients were reviewed. 1996-1997 patients underwent clinical pathway anesthesia care in which the intraoperative and postoperative anesthesia process was standardized with respect to symptom management, drugs, and equipment used. 1995-1996 patients did not have a standardized intraoperative and postoperative anesthetic course with respect to the management of common symptoms or to specific drugs and supplies used. Intervals described in the AACD Procedural Times Glossary, anesthesia drug and supply costs, and patient outcome variables (postoperative nursing interventions required and unexpected admissions), as influenced by the use of the anesthesia clinical pathway, were measured. Clinical pathway anesthesia care of ACLR in 1996-1997, which actively incorporated regional anesthesia options, reduced pharmacy and materials cost variability; slightly increased turnover time; improved intraoperative anesthesia and surgical efficiency, recovery times, and unexpected admission rates; and decreased the number of required nursing interventions for common postoperative symptoms. CONCLUSIONS: Clinical pathway patient management systems in anesthesia care are likely to produce useful outcome data of current practice patterns when compared with historical controls. This management tool may be useful in simultaneously containing costs and improving process efficiency and patient outcomes.

Adult↗
PubMed1998

Benchmarking the perioperative process: III. Effects of regional anesthesia clinical pathway techniques on process efficiency and recovery profiles in ambulatory orthopedic surgery.

STUDY OBJECTIVES: (1) To incorporate regional anesthesia options for common outpatient orthopedic surgery into clinical pathways; (2) to use the clinical pathway format and the Procedural Times Glossary published by the Association of Anesthesia Clinical Directors (AACD) as management tools to measure postoperative same-day surgery processes and discharge outcomes; and (3) to determine the effects of general, regional, and combined general-regional anesthesia on these processes and outcomes. DESIGN: Hospital database and patient chart review of consecutive patients undergoing anterior cruciate ligament reconstruction (ACLR) during academic years (AY) 1995-1996 and 1996-1997. Patient data from AY 1995-1996, during which no intraoperative anesthesia clinical pathway existed, served as historical controls. Data from AY 1996-1997, during which intraoperative anesthesia clinical pathways were used, served as the treatment group. SETTING: Ambulatory surgery center in a teaching hospital. MEASUREMENTS AND MAIN RESULTS: The records of 503 ASA physical status I and II patients were reviewed. 1996-1997 patients selected general anesthesia (+/- femoral nerve block) or epidural anesthesia, after which the remainder of the perioperative anesthesia process was standardized with respect to the drugs and equipment used. 1995-1996 patients did not necessarily have a choice in anesthesia technique and did not have a standardized perioperative anesthetic course with respect to specific drugs and supplies. Intervals described in the AACD Procedural Times Glossary, anesthesia drug and supply costs, and patient outcome variables (postoperative nursing interventions required and unexpected admissions), as influenced by anesthesia technique used, were measured. Combined general-regional anesthesia care for ACLR in 1996-1997, when compared with general anesthesia alone, led to increased pharmacy and materials costs and increased turnover time. However, patients with the combined technique showed improved recovery profiles and lower unexpected admission rates, and they required fewer nursing interventions for common postoperative symptoms. Patients receiving epidural anesthesia showed discharge outcomes similar to those patients receiving general anesthesia with femoral nerve block. Postanesthesia care unit bypass (fast-tracking) was more likely in clinical pathway regional anesthesia patients, when compared with the clinical pathway general anesthesia used. CONCLUSIONS: Clinical pathway regional anesthesia care for outpatient orthopedics may have a significant role in simultaneously containing costs and improving both process efficiency and patient outcomes.

Adult↗
PubMed1998

Occurrence of male-specific bacteriophage in feral and domestic animal wastes, human feces, and human-associated wastewaters.

Male-specific bacteriophage (MSB) densities were determined in animal and human fecal wastes to assess their potential impact on aquatic environments. Fecal samples (1,031) from cattle, chickens, dairy cows, dogs, ducks, geese, goats, hogs, horses, seagulls, sheep, and humans as well as 64 sewerage samples were examined for MSB. All animal species were found to harbor MSB, although the great majority excreted these viruses at very low levels. The results from this study demonstrate that in areas affected by both human and animal wastes, wastewater treatment plants are the principal contributors of MSB to fresh, estuarine, and marine waters.

Animals↗
PubMed1997

Benchmarking the perioperative process. I. Patient routing systems: a method for continual improvement of patient flow and resource utilization.

The article presents an overview of the design and application of a real-time patient routing system, based on barcode and local area network technology, that was designed to track the progress of patients during the perioperative process. We present data on all patients undergoing ambulatory surgery. Patients' progress during their surgical stay was recorded at 17 strategic events using this real-time patient tracking technology. These times were used to identify inefficiencies in the perioperative process by identifying bottlenecks and areas of high variation. We found that both raw and actual operating room (OR) utilization efficiency was less than 50%. Points of high variation in a patient's progress occurred during the time from admit to the hospital until the patient was ready for the OR; the time from when a patient was ready for the OR until they were called for; and the time a patient spends in the OR preoperative holding room. Causes for variation were identified and traced back to individual procedures, activities, and work processes. Multidisciplinary improvement teams were created to improve the pinpointed problem areas. The real-time patient routing system is a process that has proven to be highly valuable to all participants in the surgical process in bringing about rational, data driven efficiencies in perioperative services. This process has the potential to facilitate multidisciplinary cooperation in efforts to contain and reduce costs of perioperative services.

Appointments and Schedules↗
PubMed1997

Remifentanil versus remifentanil/midazolam for ambulatory surgery during monitored anesthesia care.

BACKGROUND: This study was designed to define the appropriate dose of remifentanil hydrochloride alone or combined with midazolam to provide satisfactory comfort and maintain adequate respiration for a monitored anesthesia care setting. METHODS: One hundred fifty-nine patients scheduled for outpatient surgery participated in this multicenter, double-blind study. Patients were randomly assigned to one of two groups: remifentanil, 1 microgram/kg, given over 30 s followed by a continuous infusion of 0.1 microgram.kg-1.min-1 (remifentanil), remifentanil, 0.5 microgram/kg, given over 30 s followed by a continuous infusion of 0.05 microgram.kg-1.min-1 (remifentanil+midazolam). Five minutes after the start of the infusion, patients received a loading dose of saline placebo (remifentanil) or midazolam, 1 mg, (remifentanil+midazolam). If patients were not oversedated, a second dose of placebo or midazolam, 1 mg, was given. Remifentanil was titrated (in increments of 50% from the initial rate) to limit patient discomfort or pain intraoperatively, and the infusion was terminated at the completion of skin closure. RESULTS: At the time of the local anesthetic, most patients in the remifentanil and remifentanil+midazolam groups experienced no pain (66% and 60%, respectively) and no discomfort (66% and 65%, respectively). The final mean (+/-SD) remifentanil infusion rates were 0.12 +/- 0.05 microgram.kg-1.min-1 (remifentanil) and 0.07 +/- 0.03 microgram.kg-1.min-1 (remifentanil+midazolam). Fewer patients in the remifentanil+midazolam group experienced nauses compared with the remifentanil group (16% vs. 36%, respectively; P < 0.05). Four patients (5%) in the remifentanil group and two patients (2%) in the remifentanil+midazolam group experienced brief periods of oxygen desaturation (SpO2 < 90%) and hypoventilation (< 8 breaths/ min). CONCLUSIONS: Remifentanil alone or combined with midazolam provided adequate analgesia and maintained adequate respiration at the doses reported. The low dose of remifentanil combined with 2 mg midazolam, compared with remifentanil alone, resulted in fewer side effects, slightly greater sedation, and less anxiety.

Adult↗
PubMed1997

A comparison of remifentanil and morphine sulfate for acute postoperative analgesia after total intravenous anesthesia with remifentanil and propofol.

BACKGROUND: The transition from remifentanil intraoperative anesthesia to postoperative analgesia must be planned carefully due to the short duration of action (3-10 min) of remifentanil hydrochloride, a potent, esterase-metabolized mu-opioid agonist. This study compared the efficacy and safety of transition regimens using remifentanil or morphine sulfate for immediate postoperative pain relief in patients who had surgery under general anesthesia with remifentanil/propofol. METHODS: One hundred fifty patients who had received open-label remifentanil and propofol for intraoperative anesthesia participated in this multicenter, double-blind, double-dummy study and were randomly assigned to either the remifentanil (R) group or the morphine sulfate (M) group. Twenty minutes before the anticipated end of surgery, the propofol infusion was decreased by 50%, and patients received either a placebo bolus (R group) or a bolus of 0.15 mg/kg morphine (M group). At the end of surgery, the propofol and remifentanil maintenance infusions were discontinued and the analgesic infusion was started: either 0.1 microg x kg(-1) x min(-1) remifentanil (R group) or placebo analgesic infusion (M group). During the 25 min after tracheal extubation, remifentanil titrations in increments of 0.025 microg x kg(-1) x min(-1) and placebo boluses (R group), or 2 mg intravenous morphine boluses and placebo rate increases (M group) were administered as necessary at 5-min intervals to control pain. Patients received the 0.075 mg/kg intravenous morphine bolus (R group) or placebo (M group) at 25 and 30 min after extubation, and the analgesic infusion was discontinued at 35 min. From 35 to 65 minutes after extubation, both groups received 2-6 mg open-label morphine analgesia every 5 min as needed. RESULTS: Successful analgesia, defined as no or mild pain with adequate respiration (respiratory rate [RR] > or =8 breaths/min and pulse oximetry > or = 90%), was achieved in more patients in the R group than in the M group (58% vs. 33%, respectively) at 25 min after extubation (P < 0.05). The median remifentanil rate for successful analgesia was 0.125 microg x kg(-1) x min(-1) (range, 0.05-0.23 microg x kg(-1) x min(-1)), and the median number of 2-mg morphine boluses used was 2 (range, 0-5 boluses). At 35 min after extubation, > or = 74% of patients in both groups experienced moderate to severe pain. Median recovery times from the end of surgery were similar between groups. Transient respiratory depression, apnea, or both were the most frequent adverse events (14% for the R group vs. 6% for the M group; P > 0.05). CONCLUSIONS: Remifentanil provided safe and effective postoperative analgesia when administered at a final rate of 0.05-0.23 microg x kg(-1) x min(-1) in the immediate postextubation period. Remifentanil provided more effective postoperative analgesia than did intraoperative treatment with morphine (0.15 mg/kg) followed by morphine boluses (< or = five 2-mg boluses). The effects of remifentanil dissipated rapidly after ending the infusion, and alternate analgesia was required. Further studies are underway to define transition regimens that will improve postoperative analgesia in patients receiving anesthesia with remifentanil.

Adult↗
PubMed1997

Principles of operating room organization.

The importance of the changing health care climate has triggered important changes in the management of high-cost components of acute care facilities. By integrating and better managing various elements of the surgical process, health care institutions are able to rationally trim costs while maintaining high-quality services. The leadership that physicians can provide is crucial to the success of this undertaking (1). The importance of the use of primary data related to patient throughput and related resources should be strongly emphasized, for only when such data are converted to INFORMATION of functional value can participating healthcare personnel be reasonably expected to anticipate and respond to varying clinical demands with ever-limited resources. Despite the claims of specific commercial vendors, no single product will likely be sufficient to significantly change the perioperative process to the degree or for the duration demanded by healthcare reform. The most effective approach to achieving safety, cost-effectiveness, and predictable process in the realm of Surgical Services will occur by appropriate application of the "best of breed" contributions of: (a) medical/patient safety practice/oversight; (b) information technology; (c) contemporary management; and (d) innovative and functional cost-accounting methodology. S "modified activity-based cost accounting method" can serve as the basis for acquiring true direct-cost information related to the perioperative process. The proposed overall management strategy emphasizes process and feedback, rather than specific product, and although imposing initial demands and change on the traditional hospital setting, can advance the strongest competitive position in perioperative services. This comprehensive approach comprises a functional basis for important bench-marking activities among multiple surgical services. An active, comparative process of this type is of paramount importance in emphasizing patient care and safety as the highest priority while changing the process and cost of perioperative care. Additionally, this approach objectively defines the surgical process in terms by which the impact of new treatments, drugs, devices and process changes can be assessed rationally.

Cost Control↗
PubMed1996

Nitric oxide mediates hepatic cytochrome P450 dysfunction induced by endotoxin.

BACKGROUND: Animals subjected to immunostimulatory conditions (sepsis) exhibit decreased total cytochrome P450 content and decreased P450-dependent drug metabolism. Cytochrome P450 function is of clinical significance because it mediates the metabolism of some opioid and hypnotic drugs. The authors tested the hypothesis that reduced P450 function and decreased drug metabolism in sepsis are mediated by endotoxin-enhanced synthesis of nitric oxide. METHODS: Hepatic microsomes were prepared from male Sprague-Dawley rats in nontreated rats, rats pretreated with phenobarbital and rats receiving aminoguanidine or NG-L-monomethyl-arginine alone. Nitric oxide synthesis was augmented for 12 h with a single injection of bacterial lipopolysaccharides. Nitric oxide synthase was inhibited with aminoguanidine or N(G)-L-monomethyl-arginine during the 12 h of endotoxemia in some animals. Plasma nitrite and nitrate concentrations were measured in vivo, and total microsomal P450 content, and metabolism of ethylmorphine and midazolam in vitro. RESULTS: Administration of endotoxin increased plasma nitrite and nitrate concentrations, decreased total cytochrome P450 content, and decreased metabolism of ethylmorphine and midazolam. Inhibition of nitric oxide formation by aminoguanidine or N(G)-L-monomethyl-arginine partially prevented the endotoxin-induced effects in the nontreated and phenobarbital-treated groups. Aminoguanidine or N(G)-L-monomethyl-arginine alone did not have an effect on either total cytochrome P450 content or P450-dependent drug metabolism. Plasma nitrite and nitrate concentrations correlated significantly negatively with P450 content (nontreated r = -0.88, phenobarbital r = -0.91), concentrations of formed formaldehyde (nontreated r = -0.87, phenobarbital r = -0.95), and concentrations of midazolam metabolites (4-OH midazolam nontreated r = -0.88, phenobarbital r = -0.93, and 1'-OH midazolam nontreated r = -0.88, phenobarbital r = -0.97). CONCLUSIONS: Altered hepatic microsomal ethylmorphine and midazolam metabolism during sepsis is mediated in large part by nitric oxide.

Animals↗
PubMed1995

Loss and degradation of enzyme-bound heme induced by cellular nitric oxide synthesis.

We report here that, like nonheme iron, protein-bound intracellular heme iron is also a target for destruction by endogenously produced nitric oxide (NO). In isolated rat hepatocytes NO synthesis results in substantial (approximately 60%) and comparable loss of catalase and cytochrome P450 as well as total microsomal heme, and decreased heme synthetic (delta-aminolevulinate synthetase and ferrochelatase) and increased degradative (heme oxygenase) enzymatic activities. The effect is reversible, and intact cytochrome P450 apoproteins are still present, as judged by heme reconstitution of isolated microsomes. The effects on delta-aminolevulinate synthetase and heme oxygenase are likely to be secondary to heme liberation, while the effects on ferrochelatase appear to be a direct effect of NO, perhaps destruction of its nonheme iron-sulfur center.

Arginine↗
PubMed1995

Nitric oxide and intracellular heme.

Figure 2 depicts a working hypothesis for these results. Activation of .NO synthesis results in nitrogen oxide-induced loss of protein-bound heme from CYP proteins, which remain relatively intact. This heme liberation results in a decrease in heme synthesis (decreased ALAS) and an increase in heme degradation (increased HO). In addition, .NO synthesis results in direct inhibition of ferrochelatase, which further contributes to inhibition of heme synthesis. There also appears to be a mechanism to repair or resynthesize CYP after .NO synthesis is inhibited. Finally, a result of this effect may be protection against cellular injury, since increased HO is an important response against cellular injury from a variety of insults.

Animals↗
PubMed1995

The operating rooms: cost center management in a managed care environment.

The changing health care climate has triggered important changes in the management of high-cost components of acute care facilities. By integrating and better managing various elements of the surgical process, health care institutions are able to rationally trim costs while maintaining high-quality services. The leadership that physicians can provide is crucial to the success of this undertaking.

Anesthesia Department, Hospital↗
PubMed1994

Opioid agonist binding affinity is increased by magnesium in the presence of guanosine diphosphate but decreased by magnesium in the presence of guanyl-5'-yl imidodiphosphate.

Opioid receptors exist in multiple affinity states for agonists. Cations and guanine nucleotides affect mu-agonist affinity by modulating the interaction between receptor molecule and G-protein. In this study, we systematically examined the effects of cations and guanine nucleotides on the binding of mu-agonist [D-Ala2, N-Me-Phe4, Met-(O)5-ol]enkephalin in rat spinal cord and brain membranes. A homogeneous class of low-affinity receptors was obtained by conducting binding assays in the presence of Na+ (100 mM) + guanosine diphosphate (100 microM). The addition of Mg++ (5 mM) shifted a portion of the low-affinity receptors to the high-affinity state. In membranes preincubated with Na+ + guanosine diphosphate and with the binding assay performed in the presence of Mg++, a homogeneous class of high-affinity receptors was induced by the agonist. Further addition of Na+ + guanyl-5'-yl imidodiphosphate (30 microM) to the above Mg++-containing medium converted all receptors to a low-affinity state, whereas Na+ + guanyl-5'-yl imidodiphosphate produced a mixture of high- and low-affinity states. Our results suggest that, depending on which guanine nucleotide is bound with G-proteins, mg++induces opposite effects on the states of mu-receptor affinity: high affinity with GDP and low affinity with guanyl-5'-yl imidodiphosphate. Sodium ion promotes the low-affinity receptor conformation and increases total low-affinity binding sites. The affinity of the opiod antagonist naloxone is not sensitive to regulation by Mg++ and guanine nucleotides, except that the total receptor binding is increased by Na+.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Microdialysis measurements of PGD2, TXB2 and 6-KETO-PGF1 alpha in rat CA1 hippocampus during transient cerebral ischemia.

We measured hippocampal CA1 concentrations of PGD2, TxB2 and 6-keto-PGF1 alpha in 18 anesthetized rats with stereotaxically implanted microdialysis probes before, during and after 20 min of global cerebral ischemia. The insertion of the microdialysis probe did not appear to cause a continuous major disturbance of arachidonic acid (AA) metabolism because stable eicosanoid concentrations were obtained prior to ischemia. During reperfusion all three eicosanoids increased significantly reaching a peak after 30-60 min and then gradually declined to baseline levels over the next 2-3 h. The ratio of average peak concentrations for PGD2, TxB2 and 6-keto-PGF1 alpha were approximately 80:2:1, respectively. The results extend previous work by demonstrating the time course of eicosanoid release in a distinct brain region and confirm the role of PGD2 as the major PG metabolite in brain. We conclude that future studies employing microdialysis may be able to provide a more detailed understanding of the role of AA metabolites in ischemic brain.

6-Ketoprostaglandin F1 alpha↗