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Brian A Williams

Publications and source records attributed to Brian A Williams.

At least 19 recordsLinked to original sources
PubMed2006

Genomic DNA as a general cohybridization standard for ratiometric microarrays.

Feature variability on ratiometric microarrays is accommodated by simultaneous cohybridization of a labeled reference standard with a labeled experimental sample. An optimal reference standard would provide full and equal representation for all array features from a given genome so that it would function on any array, would represent all features with similar signal intensity, and would be highly reproducible-both technically and biologically-from preparation to preparation and laboratory to laboratory. A low cost and a good shelf life are also highly desirable. Finally, providing for straightforward recovery of RNA prevalence information and for integration of data across multiple, initially unrelated studies would be significant advances over current methods. For virtually all ratiometric array studies published to date the reference standard has been some kind of RNA sample assembled from a number of different cell lines, tissues, or experimental time points. These RNA references fall short of the desired universality, uniformity, and reproducibility criteria, which then affect data quality and integration across studies. Also, the various mixed RNA standards cannot be used to derive RNA prevalence information from an experimental sample. In contrast, genomic DNA is a natural choice to meet all the criteria, although it has not yet been widely exploited for eukaryotic array experiments. Principal stumbling blocks have been achieving high enough absolute signals for large mammalian and plant genomes and finding a way to stabilize labeled DNA so that it can be stored and used with ease. This chapter describes two genomic DNA-labeling methods that make it possible to use genomic DNA as a universal microarray cohybridization standard. The indirect labeling method permits production of a large quantity of a stable genomic DNA standard that can then be quality tested and stored frozen. This optimizes experimental consistency and significantly improves ease of use. This chapter also shows that the genomic DNA reference standard can deliver RNA prevalence measurements from ratiometric array platforms.

Animals↗
PubMed2006

Reduction of verbal pain scores after anterior cruciate ligament reconstruction with 2-day continuous femoral nerve block: a randomized clinical trial.

BACKGROUND: Single-injection femoral nerve block analgesia and spinal anesthesia have been associated with fewer postoperative nursing interventions and successful same-day discharge after anterior cruciate ligament reconstruction. In the current study, the authors prospectively determined the effect of continuous femoral nerve block on a numeric rating scale (NRS) of pain intensity with movement for 7 postoperative days. METHODS: Patients undergoing this surgery with no history of previous invasive surgery on the same knee were recruited for this study. After standardized spinal anesthesia, intravenous sedation, and perioperative multimodal analgesia, patients received a femoral nerve catheter with (1) saline bolus (30 ml) plus saline infusion (270 ml at 5 ml/h, placebo group); (2) levobupivacaine (0.25%) bolus with saline infusion (group I), or (3) levobupivacaine (0.25%) bolus and infusion (group II). Patients were surveyed preoperatively and on postoperative days 1-4 and 7 to determine NRS scores (scale 0-10). RESULTS: Data from 233 participants were analyzed. On days 1-2, 50% of placebo patients had NRS scores of 5 or above, whereas among group II patients, only 25% had scores of 5 or above (P < 0.001). In regression models for NRS scores during days 1-4, group II was the only factor predicting lower pain scores (odds ratios, 0.3-0.5; P = 0.001-0.03). Overall, patients with preoperative NRS scores greater than 2 were likely to report higher NRS scores during days 1-7 (odds ratios, 3.3-5.2; P < 0.001). CONCLUSIONS: Femoral nerve block catheters reliably keep NRS scores below the moderate-to-severe pain threshold for the first 4 days after anterior cruciate ligament reconstruction.

Adolescent↗
PubMed2005

For outpatient rotator cuff surgery, nerve block anesthesia provides superior same-day recovery over general anesthesia.

BACKGROUND: Both general and nerve block anesthesia are effective for shoulder surgery. For outpatient surgery, it is important to determine which technique provides more efficient recovery. The authors' goal was to compare nerve block with general anesthesia with respect to recovery profile and patient satisfaction after rotator cuff surgery. METHODS: In this clinical trial, 50 consenting outpatients (aged 18-70 yr) were randomly assigned to receive either fast-track general anesthesia followed by bupivacaine (0.25%) wound infiltration or interscalene brachial plexus block (0.75% ropivacaine), each under standardized protocols. Blinded recovery room nurses assessed the need for pain treatment and rated patient eligibility for bypass of the phase 1 postanesthesia care unit and for discharge home. Patients were followed up for 2 weeks postoperatively. The primary outcome measures were postanesthesia care unit bypass and same-day discharge. Other same-day recovery outcomes included severity of and treatment for pain and time to ambulation. Postoperative outcomes at home included satisfaction with the anesthesia technique and absence of complications (at 2 weeks). RESULTS: Patients who received nerve block (vs. general anesthesia) bypassed the postanesthesia care unit more frequently (76 vs. 16%; P < 0.001), reported less pain, ambulated earlier, were ready for home discharge sooner (123 vs. 286 min; P < 0.001), had no unplanned hospital admissions (vs. 4 of 25 patients who underwent general anesthesia; P = 0.05), and were more satisfied with their care. No complications were reported in either treatment group. CONCLUSIONS: Nerve block anesthesia for outpatient rotator cuff surgery provides several same-day recovery advantages over general anesthesia.

Adolescent↗
PubMed2004

Genomic DNA as a cohybridization standard for mammalian microarray measurements.

A persistent design problem for ratiometric microarray studies is selecting the 'denominator' RNA cohybridization standard. The ideal standard should be readily available, inexpensive, invariant over time and from laboratory to laboratory, and should represent all genes with a uniform signal. RNA references (both commercial 'universal' and experiment--specific types), fall short of these goals. We show here that mouse genomic DNA is a reliable microarray cohybridization standard which can meet these criteria. Genomic DNA was superior in universality of coverage (>98% of genes from a 16,000 feature mouse 70mer microarray) to the Stratagene Universal Mouse Reference RNA standard. Ratios for genes in very low abundance in the Stratagene standard were more unstable with the Stratagene standard than with genomic DNA. Genes with mid-range, and therefore presumably optimal RNA denominator values, showed comparable reproducibility with both standards. Inferred ratios made between two different experimental RNAs using a genomic DNA standard were found to correlate well with companion, directly measured ratios (Spearman correlation coefficient = 0.98). The advantage in array feature coverage of genomic DNA will likely increase as newer generation microarrays include genes which are expressed exclusively in minor tissue or developmental domains that are not represented in mixed tissue RNA standards.

Animals↗
PubMed2004

Nausea and vomiting after outpatient ACL reconstruction with regional anesthesia: are lumbar plexus blocks a risk factor?

STUDY OBJECTIVE: To track the incidence of in-hospital postoperative nausea and vomiting (PONV) requiring postoperative parenteral nursing interventions after outpatient reconstruction of the anterior cruciate ligament (ACL) with one of two types of regional anesthesia to determine the extent to which various anesthetic techniques, preemptive antiemetics, and other factors were associated with the lowest probability of PONV. DESIGN: Retrospective chart (database) review of all ACL procedures at the University of Pittsburgh Medical Center from August 1997 through June 1999. SETTING: University medical center. MEASUREMENTS: We reviewed our institutional database of 347 consecutive patients undergoing ACL reconstruction with either spinal with femoral nerve block (SPI-FNB) or lumbar plexus and sciatic nerve block (LUM-SCI). Recorded variables and outcomes included gender, history of PONV, intravenous (i.v.) fentanyl before and during surgery, preemptive antiemetics given, and parenteral nursing interventions for PONV performed. Chi-square tests and logistic regression were used to determine factors associated with PONV. MAIN RESULTS: For SPI-FNB, PONV incidence was 13% (26/208), but it was higher for LUM-SCI [25%, 34/139, p = 0.002; odds ratio (OR) = 2.2]. Regression modeling demonstrated that women (OR = 2.8, p = 0.003) and LUM-SCI patients (OR = 3.0, p = 0.005) were at greater risk for PONV. The combination of dexamethasone (4 to 10 mg i.v.) and perphenazine (1.2 to 2.0 mg i.v.) was associated with less PONV (OR = 0.3, p = 0.005). Type of local anesthetic used for lumbar plexus block was not associated with PONV incidence. CONCLUSIONS: For ACL reconstruction with regional anesthesia, use of LUM-SCI was associated with a higher rate of PONV, whereas combination antiemetic prophylaxis with perphenazine and dexamethasone was associated with less PONV.

Adult↗
PubMed2004

Economics of nerve block pain management after anterior cruciate ligament reconstruction: potential hospital cost savings via associated postanesthesia care unit bypass and same-day discharge.

BACKGROUND: Anterior cruciate ligament reconstruction is a complex outpatient surgical procedure often associated with pain. Traditionally, the procedure is performed under general anesthesia and often requires the use of the PACU. Refractory pain and/or nausea/vomiting occasionally leads to an unplanned hospital admission. In this study, the authors examine the associations of nerve block analgesia for these patients and its associated reductions in PACU use, hospital admission, and hospital costs. METHODS: This was an observational, nonrandomized study in which existing data regarding patients' day-of-surgery outcomes were merged with hospital cost data. We reviewed a consecutive sample of 948 men and women who were in good health and underwent anterior cruciate ligament reconstruction in an outpatient surgery unit between July 1995 and June 1999. RESULTS: The use of nerve block analgesia was associated with reduced PACU admissions to 18% and decreased unplanned hospital admission rates from 17% to 4%. Multivariate linear regression analysis showed that patients bypassing the PACU had an associated hospital cost reduction of 12% (P = 0.0001), whereas patients who needed hospital admission had an associated hospital cost increase of 11% (P = 0.0003). CONCLUSIONS: The use of nerve blocks for acute pain management in patients undergoing anterior cruciate ligament reconstruction is associated with PACU bypass and reliable same-day discharge. Although the cost savings for this one procedure are unlikely to generate sufficient cost savings via staffing reductions, extrapolating these results to a large volume of all types of invasive outpatient orthopedic procedures may have the potential to create significant hospital cost savings.

Adult↗
PubMed2003

Femoral-sciatic nerve blocks for complex outpatient knee surgery are associated with less postoperative pain before same-day discharge: a review of 1,200 consecutive cases from the period 1996-1999.

BACKGROUND: Outpatient knee surgery has come to involve increasingly complex procedures. The authors present observational data from a nerve block algorithm designed for the care of outpatients undergoing knee surgery. The aim of this report is to demonstrate differences in pain and unplanned hospital admission associated with surgical complexity and nerve blocks used. METHODS: Day-of-surgery outcomes were studied for 1,200 consecutive outpatients undergoing routine arthroscopy or one of six complex outpatient knee procedures. Nerve blocks were administered on the basis of anticipated pain from open incisions in the femoral and sciatic nerve distributions. Regression analysis was used to determine factors associated with postoperative pain and unplanned hospital admissions, and patients were categorized as having received femoral and sciatic nerve blocks (FSB), femoral nerve block only (FNB), or no nerve blocks. RESULTS: Patients undergoing more complex (vs. less invasive) knee surgery were at greater risk for pain (P </= 0.004), whereas the use of FSB (vs. FNB or no block) was associated with less pain (P < 0.01). When no nerve blocks were used, more complex (vs. less invasive) knee surgery was associated with a 10-fold greater risk of hospital admission (P = 0.001). In the regression analyses, more complex surgery (P < 0.001) was associated with increased risk of admission, and the use of FNB or FSB (vs. no block) was associated with a 2.5-fold reduction in unplanned admissions (P = 0.009). CONCLUSIONS: For complex knee surgery, the use of FSB was associated with less pain; the use of FNB or FSB (vs. no block) was associated with fewer hospital admissions.

Adult↗
PubMed2003

Anesthesia and postoperative analgesia: outcomes following orthopedic surgery.

The demand for increased efficiency and decreased hospital stay has magnified the role of anesthesia and acute postoperative pain management in orthopedics. Orthopedic anesthesia and acute postoperative pain management, which are subspecialties of anesthesiology, are increasingly recognized for their positive effect on the length of hospital stay, functional recovery, and patient satisfaction. Recently, there has been a resurgence in the use of continuous nerve block techniques for postoperative pain management. These techniques have been shown to be effective and safe in controlling postoperative pain, both at rest and during physical therapy, even in anticoagulated patients. The use of peripheral nerve blocks for anesthesia has been associated with earlier discharge when compared with general anesthesia and neuraxial blocks in patients undergoing ambulatory orthopedic surgery. Regional techniques are usually part of a multimodal strategy that includes both pharmacological and nonpharmacological approaches to pain management.

Adult↗
PubMed2002

Significance and statistical errors in the analysis of DNA microarray data.

DNA microarrays are important devices for high throughput measurements of gene expression, but no rational foundation has been established for understanding the sources of within-chip statistical error. We designed a specialized chip and protocol to investigate the distribution and magnitude of within-chip errors and discovered that, as expected from theoretical expectations, measurement errors follow a Lorentzian-like distribution, which explains the widely observed but unexplained ill-reproducibility in microarray data. Using this specially designed chip, we examined a data set of repeated measurements to extract estimates of the distribution and magnitude of statistical errors in DNA microarray measurements. Using the common "ratio of medians" method, we find that the measurements follow a Lorentzian-like distribution, which is problematic for subsequent analysis. We show that a method of analysis dubbed "median of ratios" yields a more Gaussian-like distribution of errors. Finally, we show that the bootstrap algorithm can be used to extract the best estimates of the error in the measurement. Quantifying the statistical error in such measurements has important applications for estimating significance levels, clustering algorithms, and process optimization.

Algorithms↗