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Biomedical subjects

Brian Smith

Publications and source records attributed to Brian Smith.

At least 19 recordsLinked to original sources

Experimentally induced change in infectious period affects transmission dynamics in a social group.

A key component of any epidemiological model is the infectious period, which greatly affects the dynamics and persistence of an infection. Social organization, leading to behavioural and spatial heterogeneities among potential susceptibles, interacts with infectious period to create different risk categories within a group. Using the honeybee (Apis mellifera) colony as a social model, a protocol that creates different infectious periods in individual bees and another that follows the diffusion of a transmittable tracer within a colony, we show experimentally how a short infectious period results in an epidemic process with low prevalence confined only to individuals at the outer edge of a group, while a long infectious period results in high prevalence distributed more universally among all the group members. We call this finding an evidence of 'organizational immunity' in a social network and propose that the honeybee colony provides a unique opportunity to test its role in social transmission processes.

Animals↗

Gait initiation in children with cerebral palsy.

The task of gait initiation (GI), or taking a first step from a static standing position requires the development of forward momentum while maintaining dynamic balance as the body's center of mass (COM) moves forward and outside the base of support. The dynamics of GI in children (aged 7-12 years) with hemiplegic cerebral palsy (CP), diplegic CP and children with typical development (TD) were compared to characterize the mechanics and control of this task. Ground reaction forces (GRFs) and muscle activity were collected during GI at three different self-selected speeds (slow, moderate and fast). Movement of a sacral marker was also tracked to estimate downward shifting of the body during the GI task. Results demonstrate the presence of a motor sequence characterized by increased forward momentum development with increased GI speed for all groups of children. Anticipatory movements of children with CP were different when compared to children with TD. Children with hemiplegic CP demonstrated decreased lateral shifting while children with diplegic CP demonstrated a trend of decreased downward shifting of the body compared to children of TD. Analysis of the GI motor sequence in children provides a means to characterize coordination and motor control of a functional ambulatory task in children with CP compared to children with TD.

Analysis of Variance↗

Change in volume of lumpectomy cavity during external-beam irradiation of the intact breast.

PURPOSE: Definition of the lumpectomy cavity is an important component of irradiation of the breast. We use computed tomography (CT)-based planning and contour the lumpectomy volume on the planning CT. We obtained a second CT in the 4th or 5th week of treatment for boost planning and compared the volume change with the first planning-CT scan. METHODS AND MATERIALS: This retrospective study reviewed the planning-CT data for 20 patients. In the first CT, images were obtained from the mandible to 2 cm below the breast in 3-mm slices. In the second CT, for the boost, images were obtained from the top to the bottom of the clinically defined breast, in 3-mm slices. Lumpectomy cavities were contoured on both CT scans and volumes compared. RESULTS: Sixteen of the 20 patients (80%) had more than a 20% decrease from the first to the second volume, with a corresponding 95% confidence interval. The mean decrease was 16.13 cc, with a standard deviation of 14.05. The Spearman correlation coefficient of 0.18 did not show a significant correlation between the initial volume and the percent change. CONCLUSIONS: During external breast irradiation, many patients will have significant volume reduction in the lumpectomy cavity. Because CT-based definition of the lumpectomy cavity can influence the planning of a boost technique, further study appears warranted.

Breast Neoplasms↗

Mortality after major surgery for urologic cancers in specialized urology hospitals: are they any better?

PURPOSE: Specialty-specific hospitals and hospitals with a high volume of complex procedures have been shown to have better outcomes. We sought to determine whether a high volume of unrelated complex procedures or procedures in the same specialty area (urology) could translate into better outcomes after major urologic cancer surgery. METHODS: We performed a cross-sectional analysis of administrative discharge abstract data from the Nationwide Inpatient Sample of the Health Care Utilization Project for years 1998 to 2002. Comparison of outcome after three major urologic cancer-related surgical procedures (radical cystectomy [RC], radical nephrectomy [RN], and radical prostatectomy [RP]) at hospitals by procedure-specific volume, specialized urology status, and Leapfrog criteria was obtained to determine in-hospital mortality after the procedure. All patients in the database with a diagnosis of bladder, kidney, or prostate cancer being admitted for RC, RN, or RP between 1998 and 2002 were included. RESULTS: Neither specialized urology status nor meeting Leapfrog volume criteria for unrelated procedures was associated with lower odds of in-hospital mortality after any of the procedures examined. High-volume hospitals (for RC and RP) and moderate-volume hospitals (for RP) were associated with lower odds of mortality. None of the examined hospital volume-related factors was associated with lower odds of mortality after RN. CONCLUSION: In-hospital mortality after two of three major urologic cancer procedures is affected only by procedure-specific volumes. Generalized process measures existing in hospitals performing a high volume of general urologic procedures or unrelated complex procedures may be less important determinants of procedure-specific outcomes in patients.

Cross-Sectional Studies↗

High-throughput quantification for a drug mixture in rat plasma-a comparison of Ultra Performance liquid chromatography/tandem mass spectrometry with high-performance liquid chromatography/tandem mass spectrometry.

A quantitative Ultra Performance liquid chromatography/tandem mass spectrometry (UPL/MS/MS) protocol was developed for a five-compound mixture in rat plasma. A similar high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) quantification protocol was developed for comparison purposes. Among the five test compounds, three preferred positive electrospray ionization (ESI) and two preferred negative ESI. As a result, both UPLC/MS/MS and HPLC/MS/MS analyses were performed by having the mass spectrometer collecting ESI multiple reaction monitoring (MRM) data in both positive and negative ion modes during a single injection. Peak widths for most standards were 4.8 s for the HPLC analysis and 2.4 s for the UPLC analysis. There were 17 to 20 data points obtained for each of the LC peaks. Compared with the HPLC/MS/MS method, the UPLC/MS/MS method offered 3-fold decrease in retention time, up to 10-fold increase in detected peak height, with 2-fold decrease in peak width. Limits of quantification (LOQs) for both HPLC and UPLC methods were evaluated. For UPLC/MS/MS analysis, a linear range up to four orders of magnitude was obtained with r2 values ranging from 0.991 to 0.998. The LOQs for the five analytes ranged from 0.08 to 9.85 ng/mL. Three levels of quality control (QC) samples were analyzed. For the UPLC/MS/MS protocol, the percent relative standard deviation (RSD%) for low QC (2 ng/mL) ranged from 3.42 to 8.67% (N = 18). The carryover of the UPLC/MS/MS protocol was negligible and the robustness of the UPLC/MS/MS system was evaluated with up to 963 QC injections.

Animals↗

High-frequency percussive ventilation improves oxygenation in trauma patients with acute respiratory distress syndrome: a retrospective review.

BACKGROUND: High-frequency percussive ventilation (HFPV), a hybrid of conventional mechanical ventilation and high-frequency oscillatory ventilation, has been used to salvage patients with persistent hypoxemia on conventional mechanical ventilation. We hypothesized that oxygenation would improve in injured patients with severe hypoxemia who were converted to HFPV after initial management with conventional ventilation. METHODS: Chart review identified patients with acute respiratory distress syndrome (ARDS) managed with HFPV. Oxygenation parameters (oxygenation index, OI; Pao(2)/Fio(2) ratio, P/F) and mean airway pressures (mPaw) were recorded at baseline and at 1 to 4, 8 to 12, and 12 to 24 hours after initiation of HFPV. Values at baseline and each time point after conversion to HFPV were compared by using analysis of variance or Kruskal-Wallis tests. RESULTS: Twelve patients, over 24 months, were reviewed. Baseline measurements were OI: 42.2 +/- 33, P/F: 70 +/- 31, (median +/- interquartile range), and mPaw: 29 +/- 8 (mean +/- standard deviation) cm H(2)O. After initiation of HFPV, mPaw did not differ from baseline. There was an improvement in OI (P = .01) from baseline at 12 to 24 hours after initiation of HFPV and in P/F at 12 to 24 hours (P = .002) and 8 to 12 hours (P = .001) after initiation of HFPV. CONCLUSIONS: HFPV may improve oxygenation in patients with ARDS without a concomitant increase in mPaw. A randomized trial of HFPV versus conventional ventilation in trauma patients is needed.

Adult↗

Checking the anaesthetic machine.

Making sure that anaesthetic equipment is working correctly is an essential part of the anaesthetic practitioner's role. During induction of anaesthesia the patient is at one of the most vulnerable points in his or her perioperative care. This is the point at which equipment error may put the patient at high risk of harm, for example, through compromising the airway, causing circulatory problems, preventing satisfactory oxygenation or even causing death. Many writers have drawn comparisons between anaesthesia and aviation, with the suggestion that practitioners should check the anaesthetic machines using a 'cockpit drill' (Ranasinghe 2000). The purpose of this detailed check is to ensure the machine is safe to use. The careful attention to the check is a reflection of good practice which the practitioner's codes of professional practice demand (HPC 2004, NMC 2004). This article discusses the importance of following the anaesthetic checklist to the recommended standards for both the practitioner and the patient.

Anesthesia↗

Pleiotropic effects of statins: benefit beyond cholesterol reduction? A meta-regression analysis.

OBJECTIVES: This study sought to determine whether statins reduce coronary heart disease (CHD) risk more than other interventions that also primarily lower low-density lipoprotein cholesterol (LDL-C). BACKGROUND: Statins have anti-inflammatory, immunomodulatory, antithrombotic, vascular, and other non-LDL-C-lowering effects. It is unclear whether these pleiotropic effects contribute to cardiovascular risk reduction beyond that expected from LDL-C reduction alone. METHODS: Trials published in English language journals were retrieved by searching Medline (1966 to October 2004), bibliographies, and the author's reference files. Randomized, placebo-controlled trials of interventions to primarily lower LDL-C of three or more years' duration in which clinical disease or death were primary outcomes were used. Information on sample size, treatment type and duration, participant characteristics at baseline, reduction in lipids, and outcome was independently abstracted by two authors (J.R. and N.M.) using a standardized protocol. Data from 5 diet, 3 bile acid sequestrant, 1 surgery, and 10 statin trials, with 81,859 participants, were included in the CHD meta-regression analysis. RESULTS: The regression lines for non-statin and statin trials were similar and consistent with a one-to-one relationship between LDL-C lowering and CHD and stroke reduction over five years of treatment. CONCLUSIONS: The pleiotropic effects of statins do not seem to contribute an additional cardiovascular risk reduction benefit beyond that expected from the degree of LDL-C lowering observed in other trials that primarily lowered LDL-C.

Cholesterol, LDL↗

Regulation of p21(WAF1/CIP1) stability by WISp39, a Hsp90 binding TPR protein.

p21(WAF1/CIP1), a cyclin-dependent kinase inhibitor and a critical regulator of cell cycle, is controlled transcriptionally by p53-dependent and -independent mechanisms and posttranslationally by the proteasome. We have identified WISp39, a tetratricopeptide repeat (TPR) protein that binds p21. WISp39 stabilizes newly synthesized p21 protein by preventing its proteasomal degradation. WISp39, p21, and hsp90 form a trimeric complex in vivo. The interaction of WISp39 with Hsp90 is abolished by point mutations within the C-terminal TPR domain of WISp39. Although this WISp39 TPR mutant binds p21 in vivo, it fails to stabilize p21. Our results suggest that WISp39 recruits Hsp90 to regulate p21 protein stability. WISp39 downregulation by siRNA prevents the accumulation of p21 and cell cycle arrest after ionizing radiation. The results demonstrate the importance of posttranslational stabilization of p21 protein by WISp39 in regulating cellular p21 activity.

Amino Acid Sequence↗

Effect of paroxetine hydrochloride (Paxil) on fatigue and depression in breast cancer patients receiving chemotherapy.

BACKGROUND: Fatigue can significantly interfere with a cancer patient's ability to fulfill daily responsibilities and enjoy life. It commonly co-exists with depression in patients undergoing chemotherapy, suggesting that administration of an antidepressant that alleviates symptoms of depression could also reduce fatigue. METHODS: We report on a double-blind clinical trial of 94 female breast cancer patients receiving at least four cycles of chemotherapy randomly assigned to receive either 20 mg of the selective serotonin re-uptake inhibitor (SSRI) paroxetine (Paxil, SmithKline Beecham Pharmaceuticals) or an identical-appearing placebo. Patients began their study medication seven days following their first on-study treatment and continued until seven days following their fourth on-study treatment. Seven days after each treatment, participants completed questionnaires measuring fatigue (Multidimensional Assessment of Fatigue, Profile of Mood States-Fatigue/Inertia subscale and Fatigue Symptom Checklist) and depression (Profile of Mood States-Depression subscale [POMS-DD] and Center for Epidemiologic Studies-Depression [CES-D]). RESULTS: Repeated-measures ANOVAs, after controlling for baseline measures, showed that paroxetine was more effective than placebo in reducing depression during chemotherapy as measured by the CES-D (p = 0.006) and the POMS-DD (p = 0.07) but not in reducing fatigue (all measures, ps > 0.27). CONCLUSIONS: Although depression was significantly reduced in the 44 patients receiving paroxetine compared to the 50 patients receiving placebo, indicating that a biologically active dose was used, no significant differences between groups on any of the measures of fatigued were observed. Results suggest that modulation of serotonin may not be a primary mechanism of fatigue related to cancer treatment.

Adult↗

Acustimulation wrist bands are not effective for the control of chemotherapy-induced nausea in women with breast cancer.

This experiment examined the efficacy of an acustimulation wrist band for the relief of chemotherapy-induced nausea using a randomized three-arm clinical trial (active acustimulation, sham acustimulation, and no acustimulation) in 96 women with breast cancer who experienced nausea at their first chemotherapy treatment. Five outcomes related to wrist band efficacy (acute nausea, delayed nausea, vomiting, QOL, and total amount of antiemetic medication used) were examined. The five outcomes were examined separately using analysis of covariance controlling for age and severity of past nausea. There were no significant differences in any of these study measures among the three treatment conditions (P>0.1 for all). Study results do not support the hypothesis that acustimulation bands are efficacious as an adjunct to pharmacological antiemetics for control of chemotherapy-related nausea in female breast cancer patients.

Acupuncture Therapy↗

High-frequency oscillatory ventilation in adults: respiratory therapy issues.

OBJECTIVE: To summarize clinical information and assessment techniques relevant to respiratory therapists caring for adult patients on high-frequency oscillatory ventilation (HFOV). DATA SOURCE: Review of observational studies, controlled trials, case reports, institutional experience, and hospital HFOV guidelines for adult patients. DATA SUMMARY: Respiratory therapists require unique physical assessment skills and knowledge in managing patients on HFOV. Respiratory therapy procedures relevant to HFOV include setting endotracheal tube cuff leaks, performing lung recruiting maneuvers, endotracheal suctioning, and monitoring ventilator parameters. Respiratory therapists serve as essential team members in the creation and implementation of written HFOV guidelines (e.g., algorithms) to optimize patient care. CONCLUSION: Respiratory therapy assessment and procedural skills are essential in providing optimal care to adult patients on HFOV.

High-Frequency Ventilation↗