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Biomedical subjects

Robert A Smith

Publications and source records attributed to Robert A Smith.

At least 19 recordsLinked to original sources
PubMed2026

Investigating genetic susceptibility to concussion through rare variants in ion channel and neurotransmission genes.

Some individuals appear more susceptible to concussion or mild traumatic brain injury (mTBI) and the severity, range, and the persistence of post-concussion symptoms vary considerably between affected individuals. Genetic factors are likely to contribute to this variability. Symptomatic overlap of post-concussion syndrome with neurological conditions such as familial hemiplegic migraine (FHM) caused by rare pathogenic variants in ion channel and synapse protein genes, with high sensitivity to head trauma for some patients, suggests that variation in similar pathways may influence concussion susceptibility and recovery. To investigate this hypothesis, we performed whole exome sequencing in 93 unrelated individuals who had sustained a single or multiple concussions and examined rare protein-altering variants in FHM genes, other neuronal ion channel and transporter genes, and genes involved in neurotransmission. We identified 62 different rare missense variants across 24 genes in 59 participants (63%), with 26 individuals carrying 2 or more variants. The prevalence of specific likely damaging rare variants in the 16 ion channel-related genes that were identified was approximately fivefold higher than that observed from gnomAD population controls (Odds Ratio = 5.44, 95% CI [4.13,7.18], P < 0.0001). Notably, voltage-gated calcium and sodium channel genes, including SCN9A, together with neurotransmission-related genes such as SNCAIP, harboured multiple potentially deleterious variants. These findings suggest that rare deleterious variants in genes involved in ion homeostasis and neurotransmission may contribute to an individual's susceptibility to concussion or more severe post-concussion symptoms. This study provides a foundation for future genetic and functional investigations aimed at improving our understanding of concussion susceptibility and outcomes. Further validation in larger cohorts and mechanistic studies is warranted to determine their utility as biomarkers of concussion risk and prognosis.

Humans↗
PubMed2006

Cell death in rat cerebellar granule neurons induced by hydrogen peroxide in vitro: mechanisms and protection by adenosine receptor ligands.

Oxidative stress, resulting from excessive production of reactive oxygen species (ROS), is a pathological state that causes profound cellular damage and eventual death resulting from the overactivation of glutamate receptors, and the generation of nitric oxide, superoxide and hydrogen peroxide (H(2)O(2)). As such, H(2)O(2) represents an important model for studying the neuropathology of oxidative stress in a variety of CNS disorders. The effects of H(2)O(2) on the viability of post-natal cerebellar granule neurons (CGNs), the nature of the cell death involved and the potential protection by adenosine receptors against the damage were examined in the current study. Hydrogen peroxide (10-400 microM) reduced CGN viability in a concentration- and time-dependent manner. The addition of catalase (100 U/ml) prevented this effect, and the non-specific COX inhibitor aspirin (1 mM) also alleviated the damage. A combination of H(2)O(2) (5 microM) and Cu(2+) (0.5 mM) resulted in a significant damage that was not prevented by the hydroxyl radical scavenger mannitol (50 mM). The permeability transition pore blocker cyclosporin A, the caspase-3 inhibitor Z-DEVD-fmk (40 microM) and the PARP-1 inhibitor DPQ (10 microM) each significantly protected against peroxide damage. While the A(1) adenosine receptor agonist CPA and the A(2A) receptor antagonist ZM241385 (each at 100 nM) elicited protection, the A(1) adenosine receptor blocker DPCPX and the A(2A) receptor agonist CGS21680 (each at 100 nM) showed no effect. The data demonstrate that H(2)O(2) induced oxidative stress in CGNs, involving both apoptotic and necrotic death, and this can be ameliorated by A(1) receptor activation or A(2A) receptor blockade.

Adenosine↗
PubMed2006

The effect of addition of nitrous oxide to a sevoflurane anesthetic on BIS, PSI, and entropy.

OBJECTIVE: N(2)O is a commonly used anesthetic that has amnestic and analgesic properties. Recently, devices that estimate depth of consciousness have been introduced in an attempt to better titrate anesthesia, however the effect of N(2)O on these monitors is unclear. METHODS: General anesthesia was induced and titrated to maintain normal blood pressure and pulse in healthy adults. Data were collected in three 10 minute intervals (Sevo, Sevo + N(2)O, Sevo). In Phase A, sevoflurane concentration was held constant during the N(2)O trial in 60 subjects monitored with either BIS, PSI, or Entropy. In Phase B, sevoflurane concentration was reduced as N(2)O was added, maintaining a constant overall "MAC" in 20 subjects monitored concurrently with BIS and Entropy. Sample size for both phases was designed to detect a 10 unit change in measure of processed EEG with alpha = .05 and statistical power = .80. RESULTS: In Phase A, supplementing sevoflurane with > 65% N(2)O increased MAC from 1.3 +/- 0.05 to 2.2 +/- 0.10, but did not significantly alter BIS nor PSI (p-value for differential MAC is < 0.05). Entropy, however, dropped significantly, with a change in state entropy (SE) from 31.1 +/- 7.3 to 18.9 +/- 3.7 and a corresponding rise when N(2)O was discontinued. In Phase B, supplementing sevoflurane with > 65% N(2)O with a concomitant reduction in sevoflurane resulted in an increase in both BIS (from 34 +/- 5 to 53.9 +/- 11.5) and SE (from 32 +/- 8.2 to 55.4 +/- 21.3). CONCLUSION: Supplementing sevoflurane with > 65% N(2)O did not result in a significant change in either BIS or PSI when sevoflurane concentration was kept constant. Entropy, however, significantly decreased as anesthetic depth increased. When sevoflurane concentration was reduced during N(2)O administration, both BIS and Entropy rose despite maintenance of anesthetic depth, indicating a variable concentration effect between volatiles and N(2)O.

Adult↗
PubMed2006

Hydrogen peroxide-induced oxidative stress in MC3T3-E1 cells: The effects of glutamate and protection by purines.

Glutamate has toxic effects on a number of tissues, partly by inducing toxic (e.g., oxidative) stress, whereas adenosine can be protective. Since there is evidence that glutamate and adenosine receptors are present in bone, we set out to study whether oxidative stress, induced by hydrogen peroxide (H2O2), affected viability in the MC3T3-E1 osteoblast-like cell line and whether treatment with adenosine receptor ligands attenuated this. Hydrogen peroxide (100 microM to 5 mM) reduced the viability of the MC3T3-E1 cells, while catalase reversed this cell loss and itself had some mitogenic effect. Superoxide dismutase (SOD) increased the number of viable cells alone but failed to modify significantly the effect of H2O2 treatments. Glutamate (100 microM, 1 mM) and NMDA (10 microM), applied alone for up to 1 h, had a mitogenic effect (P < 0.05). Adenosine A1 and A2A receptor agonists and antagonists at low and high concentrations showed some mitogenic effects when added singly, but only high concentrations of the agonists showed significant protection against cell death resulting from H2O2 treatments. Contributions from both apoptotic and necrotic pathways were implicated in the H2O2-induced cell loss as was demonstrated by the use of the caspase-3 inhibitor (Z-DEVD-fmk) and the PARP-1 inhibitor (DPQ). The results demonstrate that hydrogen peroxide was toxic to MC3T3-E1 cells, whereas glutamate was not and may even have a trophic influence. Adenosine and its receptors afforded some protection to osteoblasts against cellular death mediated partly by apoptosis and partly by necrosis.

Alkaline Phosphatase↗
PubMed2006

Nonrespiratory diseases of stocker cattle.

Bovine respiratory disease is the most common health issue affecting stocker cattle. There are several nonrespiratory diseases that affect stockers. The more common diseases include rumen tympany, infectious bovine keratoconjunctivitis, coccidiosis, photosensitization, and foot rot. Accurate diagnosis, early treatment, and incorporating appropriate preventive measures can assist cattle production.

Animals↗
PubMed2006

Guidelines for colonoscopy surveillance after polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society.

Adenomatous polyps are the most common neoplastic findings discovered in people who undergo colorectal screening or who have a diagnostic work-up for symptoms. It was common practice in the 1970s for these patients to have annual follow-up surveillance examinations to detect additional new adenomas and missed synchronous adenomas. As a result of the National Polyp Study report in 1993, which showed clearly in a randomized design that the first postpolypectomy examination could be deferred for 3 years, guidelines published by a gastrointestinal consortium in 1997 recommended that the first follow-up surveillance take place 3 years after polypectomy for most patients. In 2003 these guidelines were updated and colonoscopy was recommended as the only follow-up examination, stratification at baseline into low risk and higher risk for subsequent adenomas was suggested. The 1997 and 2003 guidelines dealt with both screening and surveillance. However, it has become increasingly clear that postpolypectomy surveillance is now a large part of endoscopic practice, draining resources from screening and diagnosis. In addition, surveys have shown that a large proportion of endoscopists are conducting surveillance examinations at shorter intervals than recommended in the guidelines. In the present report, a careful analytic approach was designed to address all evidence available in the literature to delineate predictors of advanced pathology, both cancer and advanced adenomas, so that patients can be stratified more definitely at their baseline colonoscopy into those at lower risk or increased risk for a subsequent advanced neoplasia. People at increased risk have either 3 or more adenomas, high-grade dysplasia, villous features, or an adenoma 1 cm or larger in size. It is recommended that they have a 3-year follow-up colonoscopy. People at lower risk who have 1 or 2 small (<1 cm) tubular adenomas with no high-grade dysplasia can have a follow-up evaluation in 5-10 years, whereas people with hyperplastic polyps only should have a 10-year follow-up evaluation, as for average-risk people. There have been recent studies that have reported a significant number of missed cancers by colonoscopy. However, high-quality baseline colonoscopy with excellent patient preparation and adequate withdrawal time should minimize this and reduce clinicians concerns. These guidelines were developed jointly by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society to provide a broader consensus and thereby increase the use of the recommendations by endoscopists. The adoption of these guidelines nationally can have a dramatic impact on shifting available resources from intensive surveillance to screening. It has been shown that the first screening colonoscopy and polypectomy produces the greatest effects on reducing the incidence of colorectal cancer in patients with adenomatous polyps.

Adenomatous Polyposis Coli↗
PubMed2006

Guidelines for colonoscopy surveillance after cancer resection: a consensus update by the American Cancer Society and the US Multi-Society Task Force on Colorectal Cancer.

Patients with resected colorectal cancer are at risk for recurrent cancer and metachronous neoplasms in the colon. This joint update of guidelines by the American Cancer Society and the US Multi-Society Task Force on Colorectal Cancer addresses only the use of endoscopy in the surveillance of these patients. Patients with endoscopically resected Stage I colorectal cancer, surgically resected Stages II and III cancers, and Stage IV cancer resected for cure (isolated hepatic or pulmonary metastasis) are candidates for endoscopic surveillance. The colorectum should be carefully cleared of synchronous neoplasia in the perioperative period. In nonobstructed colons, colonoscopy should be performed preoperatively. In obstructed colons, double-contrast barium enema or computed tomography colonography should be performed preoperatively, and colonoscopy should be performed 3 to 6 months after surgery. These steps complete the process of clearing synchronous disease. After clearing for synchronous disease, another colonoscopy should be performed in 1 year to look for metachronous lesions. This recommendation is based on reports of a high incidence of apparently metachronous second cancers in the first 2 years after resection. If the examination at 1 year is normal, then the interval before the next subsequent examination should be 3 years. If that examination is normal, then the interval before the next subsequent examination should be 5 years. Shorter intervals may be indicated by associated adenoma findings (see "Guidelines for Colonoscopy Surveillance After Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society"). Shorter intervals also are indicated if the patient's age, family history, or tumor testing indicate definite or probable hereditary nonpolyposis colorectal cancer. Patients undergoing low anterior resection of rectal cancer generally have higher rates of local cancer recurrence compared with those with colon cancer. Although effectiveness is not proven, performance of endoscopic ultrasound or flexible sigmoidoscopy at 3- to 6-month intervals for the first 2 years after resection can be considered for the purpose of detecting a surgically curable recurrence of the original rectal cancer.

Colectomy↗
PubMed2006

Hypersusceptibility to substrate analogs conferred by mutations in human immunodeficiency virus type 1 reverse transcriptase.

Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) contains four structural motifs (A, B, C, and D) that are conserved in polymerases from diverse organisms. Motif B interacts with the incoming nucleotide, the template strand, and key active-site residues from other motifs, suggesting that motif B is an important determinant of substrate specificity. To examine the functional role of this region, we performed "random scanning mutagenesis" of 11 motif B residues and screened replication-competent mutants for altered substrate analog sensitivity in culture. Single amino acid replacements throughout the targeted region conferred resistance to lamivudine and/or hypersusceptibility to zidovudine (AZT). Substitutions at residue Q151 increased the sensitivity of HIV-1 to multiple nucleoside analogs, and a subset of these Q151 variants was also hypersusceptible to the pyrophosphate analog phosphonoformic acid (PFA). Other AZT-hypersusceptible mutants were resistant to PFA and are therefore phenotypically similar to PFA-resistant variants selected in vitro and in infected patients. Collectively, these data show that specific amino acid replacements in motif B confer broad-spectrum hypersusceptibility to substrate analog inhibitors. Our results suggest that motif B influences RT-deoxynucleoside triphosphate interactions at multiple steps in the catalytic cycle of polymerization.

Amino Acid Motifs↗
PubMed2006

The effect of ravuconazole on the pharmacokinetics of nelfinavir in healthy male volunteers.

An open-label, nonrandomized study was conducted to assess the effect of ravuconazole on the pharmacokinetics of concomitantly administered nelfinavir. Healthy volunteers received 750 mg nelfinavir on day 1, 750 mg nelfinavir and 400 mg ravuconazole on day 2, 400 mg ravuconazole on days 3 to 28, and 750 mg nelfinavir and 400 mg ravuconazole on day 29. The geometric means of C(max) and area under the curve of nelfinavir coadministered with ravuconazole were 30.7% and 31.9% higher on day 2 and 7.9% and 16.2% lower on day 29, respectively, compared to the corresponding values on day 1. These findings are consistent with the potential for ravuconazole to both inhibit and induce CYP3A isozymes. The alterations in the systemic exposure to nelfinavir were within the range defined by the 90% confidence interval. The study data indicate that coadministration of ravuconazole did not result in a clinically significant change in the plasma levels of nelfinavir.

Adolescent↗
PubMed2006

Entecavir pharmacokinetics, safety, and tolerability after multiple ascending doses in healthy subjects.

A double-blind, placebo-controlled, multiple oral dose escalation study was conducted to investigate the pharmacokinetics, safety, and tolerability of entecavir in healthy subjects. Eight subjects were assigned to each of the 3 dose panels (0.1 mg, 0.5 mg, and 1 mg or matched placebo once daily for 14 days). Blood and urine samples were collected for pharmacokinetic analyses. Entecavir was rapidly absorbed, with peak plasma concentration occurring within 1 hour of dosing. Steady-state plasma concentrations of entecavir were achieved by 10 days following the initial dose. At steady state, the mean area under the plasma concentration-time curve over 1 dosing interval, increased approximately proportional to dose. Entecavir had a mean terminal half-life ranging from 128 to 149 hours and an effective half-life of approximately 24 hours. Elimination was predominantly through renal excretion, with mean urinary recovery ranging from 62% to 73%. Entecavir was safe and well tolerated when administered at doses ranging from 0.1 mg to 1 mg/d for 14 days.

Adult↗
PubMed2006

Cancer screening in the USA.

Once screening for cancer has been shown to be effective, reducing cancer morbidity and mortality in the population depends on the successful delivery of mass screening. Today, screening for cancer may be achieved through the organized delivery of services, or unsystematically, by individual referral for screening at intervals which are not necessarily optimal or regularly spaced. Organized screening is distinguished from unsystematic screening primarily on the basis of how the offer of screening occurs--whether by invitation, issued from centralized population registers or coincidently, depending on individuals seeking screening on their own, or having providers initiate screening during visits for care for other reasons. This manuscript describes cancer screening in the USA, which for most Americans is unsystematic. While this model can achieve many of the goals of screening, these goals are achieved at a greater cost, less efficiently, and without the assurance of full participation of the entire, eligible population. In order to achieve the fullest potential of cancer screening in the most cost-effective manner, screening should be organized, with attention to monitoring the fullest performance of the programme from recruitment to follow-up.

Adolescent↗
PubMed2005

Recombinant bovine interleukin 2 enhances immunity and protection induced by Brucella abortus vaccines in cattle.

Augmentation of immunization of cattle Brucella abortus S19 or a B. abortus soluble protein extract (SPEBA) vaccine through administration of recombinant bovine IL 2 (rBoIL 2) was evaluated. Seventy-five heifers were divided among 6 groups that were treated with the following: Group 1, no treatment; Group 2, rBoIL 2 (1microg/kg) on day 0; Group 3, SPEBA (2 mg) on day 0 and week 9; Group 4, SPEBA + rBoIL 2 on day 0, SPEBA on week 9; Group 5, S19 (10(7) CFU) on day 0 and week 9; Group 6, S19 + rBoIL 2 on day 0, S19 only on week 9. Approximately, 6 months after vaccination, cattle were bred by natural service, and at mid-gestation pregnant cattle were challenged intraconjunctivally with 9.1 x 10(5) CFU of virulent B. abortus S2308. Pre- and post-challenge antibody responses were measured by an enzyme-linked immunosorbent assay, a particle concentration fluorescence assay, and the card test. Lymphoproliferation (LP) responses to gamma-irradiated B. abortus and SPEBA antigens were measured in peripheral blood mononuclear cells. After vaccination, antibody responses to B. abortus elevated rapidly in SPEBA- and S19-vaccinates with and without rBoIL 2, however, these responses were significantly (P < 0.05) higher in vaccinates which also received rBoIL 2. Antibody levels for all vaccinated groups had returned to those of negative control groups by the challenge date with the exception of the SPEBA/rBoIL 2 group. In general, LP responses were higher in vaccinated or rBoIL 2-treated cattle than for unvaccinated controls. Challenge of 48 pregnant heifers resulted in abortions in 4/9 of Group 1, 0/9 of Group 2, 4/8 of Group 3, 2/9 of Group 4, 1/7 of Group 5, and 0/6 of Group 6 cattle. Treatment with rBoIL 2 alone (Group 2) provided significant (P < 0.05) protection from infection, abortions and induction of sero-positive status compared to untreated (Group 1) cattle. Co-administration of rBoIL 2 with S19 resulted in significant (P < 0.05) augmentation in onset, duration and magnitude of LP responses to B. abortus antigens following challenge. Characterization of the cytokine response of bovine monocyte-derived macrophages by real-time polymerase chain reaction indicated that in vitro stimulation of these cells with rBoIL 2 resulted in a profound up-regulation of genes encoding tumor necrosis factor-alpha, IL 12p40, and interferon-gamma reflecting activation of the cells. Overall, rBoIL 2-treatment was associated with fewer infections, sero-conversions and a significant (P = 0.02) level of protection against abortion as compared to vaccination alone or no treatment.

Abortion, Veterinary↗
PubMed2005

Professional and economic factors affecting access to mammography: a crisis today, or tomorrow? Results from a national survey.

BACKGROUND: Objective data and anecdotal reports have suggested that access to mammography may be declining because of facility closures and difficulty in recruiting and retaining radiologists and radiologic technologists. To gain insight into the practice patterns, use of emerging technologies, and concerns of breast imagers in current practice, the Society of Breast Imaging (SBI) conducted a national survey of breast imaging practices in the U.S. METHODS: Between October 2003 and April 2004, the SBI conducted a survey of the SBI membership database, and received completed surveys from 575 breast imaging practices in the U.S. Responses to the survey regarding practice characteristics, the utilization of standard and emerging technologies, staffing, malpractice, finance, and morale were analyzed. RESULTS: Job vacancies for radiologists who read mammograms were reported in 163 practices (29%), 59 of which (10%) had 2 or more openings. A higher proportion of practices with job openings had long appointment waiting times for asymptomatic women when compared with fully staffed practices. Unfilled fellowship positions also were common, with 41 of 65 practices that offer fellowships reporting 47 openings. Among 554 responding practices, 55% reported that someone in their practice was sued because of a mammography related case within the past 5 years, and 50% of practices reported that the threat of lawsuits made radiologist staffing "moderately" or "a lot" more difficult. Of 521 responding practices, 35% reported financial losses in 2002. One in 5 respondents reported that they would prefer to spend less time in mammography, and fewer than 1 in 3 would recommend a breast imaging fellowship to a relative or friend. Emerging technologies, such as breast magnetic resonance imaging and screening ultrasound, currently are being performed in many practices. CONCLUSIONS: The survey results provide support for anecdotal reports that breast imaging practices face significant challenges and stresses, including shortages of key personnel, a lack of trainees, malpractice concerns, financial constraints, increased workload due to emerging technologies, low appeal of breast imaging as a career specialty, and the steady rise in the population of women of screening age.

Breast Neoplasms↗
PubMed2005

Detection of mRNA levels for the estrogen alpha, estrogen beta and androgen nuclear receptor genes in archival breast cancer tissue.

Previous studies in our laboratory have shown association of nuclear receptor expression and histological breast cancer grade. To further investigate these findings, it was the objective of this study to determine if expression levels of the estrogen alpha, estrogen beta and androgen nuclear receptor genes varied in different breast cancer grades. RNA extracted from paraffin embedded archival breast tumour tissue was converted into cDNA and cDNA underwent PCR to enable quantitation of mRNA expression. Expression data was normalised against the 18S ribosomal gene multiplex and analysed using ANOVA. Analysis indicated a significant alteration of expression for the androgen receptor in different cancer grades (P=0.014), as well as in tissues that no longer possess estrogen receptor alpha proteins (P=0.025). However, expression of estrogen receptors alpha and beta did not vary significantly with cancer grade (P=0.057 and 0.622, respectively). Also, the expression of estrogen receptor alpha or beta did not change, regardless of the presence of estrogen receptor alpha protein in the tissue (P=0.794 and 0.716, respectively). Post-hoc tests indicate that the expression of the androgen receptor is increased in estrogen receptor negative tissue as well as in grade 2 and grade 3 tumours, compared to control tissue. This increased expression in late stage breast tumours may have implications to the treatment of breast tumours, particularly those lacking expression of other nuclear receptor genes.

Breast Neoplasms↗
PubMed2005

Borate-catalyzed reactions of hydrogen peroxide: kinetics and mechanism of the oxidation of organic sulfides by peroxoborates.

The kinetics of the oxidation of substituted phenyl methyl sulfides by hydrogen peroxide in borate/boric acid buffers were investigated as a function of pH, total peroxide concentration, and total boron concentration. Second-order rate constants at 25 degrees C for the reaction of methyl 4-nitrophenyl sulfide and H(2)O(2), monoperoxoborate, HOOB(OH)(3) (-), or diperoxoborate, (HOO)(2)B(OH)(2) (-), are 8.29 x 10(-5), 1.51 x 10(-2) and 1.06 x 10(-2) M(-1) s(-1), respectively. Peroxoboric acid, HOOB(OH)(2), is unreactive. The Hammett rho values for the reactions of a range of substituted phenyl methyl sulfides and hydrogen peroxide, monoperoxoborate or diperoxoborate are -1.50 +/- 0.1, -0.65 +/- 0.07 and -0.48 (two points only), respectively. The rho values for the peroxoborates are of significantly lower magnitude than expected from their reactivity compared to other peroxides. Nevertheless the negative rho values indicate positive charge development on the sulfur atom in the transition state consistent with nucleophilic attack by the organic sulfides on the peroxoborates as with the other peroxides. The kinetic parameters, including the lack of reactivity of peroxoboric acid, are discussed in terms of the differences in the transition state of reactions involving peroxoboron species with respect to those of other peroxides.

Borates↗
PubMed2005

A national survey of primary care physicians' methods for screening for fecal occult blood.

BACKGROUND: Screening with the fecal occult blood test (FOBT) has been shown to reduce colorectal cancer incidence and mortality in randomized, controlled trials. Although the test is simple, implementation requires adherence to specific techniques of testing and follow-up of abnormal results. OBJECTIVE: To examine how FOBT and follow-up are conducted in community practice across the United States. DESIGN: Cross-sectional national surveys of primary care physicians and the public. SETTING: The Survey of Colorectal Cancer Screening Practices in Health Care Organizations and the 2000 National Health Interview Survey. PARTICIPANTS: 1147 primary care physicians who ordered or performed FOBT and 11 365 adults 50 years of age or older who responded to questions about FOBT use. MEASUREMENTS: Self-reported data on details of FOBT implementation and follow-up of positive results. RESULTS: Although screening guidelines recommend home tests, 32.5% (95% CI, 29.8% to 35.3%) of physicians used only the less accurate method of single-sample in-office testing; another 41.2% (CI, 38.3% to 44.0%) used both types of test. Follow-up of positive test results showed considerable nonadherence to guidelines, with 29.7% (CI, 27.1% to 32.4%) of physicians recommending repeating FOBT. Furthermore, sigmoidoscopy, rather than total colon examination, was commonly recommended to work up abnormal findings. Nearly one third of adults who reported having FOBT said they had only an in-office test, and nearly one third of those who reported abnormal FOBT results reported no follow-up diagnostic procedures. LIMITATIONS: The study was based on self-reports. Data from the National Health Interview Survey may underestimate the prevalence of in-office testing and inadequate follow-up. CONCLUSIONS: Mortality reductions demonstrated with FOBT in clinical trials may not be realized in community practice because of the common use of in-office tests and inappropriate follow-up of positive results. Education of providers and system-level interventions are needed to improve the quality of screening implementation.

Colorectal Neoplasms↗
PubMed2005

Constant positive airway pressure reduces hypoventilation induced by inhalation anesthesia.

STUDY OBJECTIVE: To discover if reducing respiratory system impedance would increase tidal volume and improve ventilation during inhalation anesthesia. DESIGN: Prospective, randomized cross-over study. SUBJECTS: Nine ASA physical status I and II adult female oncology patients undergoing breast operations with or without lymph node dissection and general anesthesia while breathing spontaneously. INTERVENTIONS AND MEASUREMENTS: Patients underwent alternating trials of constant positive airway pressure, with or without pressure support. Constant positive airway pressure and pressure support were titrated to maximize respiratory system compliance and equal inspiratory pressure gradient across tracheal tube, respectively. Variables reflecting cardiovascular function, pulmonary mechanics and lung gas exchange, and respired gases and isoflurane concentrations were measured. MAIN RESULTS: End-tidal concentration of isoflurane (1.3 +/- 0.2%), Fio(2) (0.43 +/- 0.09 ), and CO(2) elimination (209 +/- 42 mL min(-1)) was unchanged throughout study in patients aged 63 +/- 12 years, weighing 72 +/- 12 kg. Constant positive airway pressure (12 +/- 2 cm H(2)O) increased respiratory system compliance from 52 +/- 8 to 80 +/- 9 mL cm H(2)O(-1) (P < .001), tidal volume from 156 +/- 32 to 325 +/- 52 mL (P < .001), and minute ventilation from 4.37 +/- 0.86 to 6.18 +/- 0.92 L min(-1) (P < .001). Respiratory rate decreased from 29 +/- 7 to 19 +/- 2 min(-1) (P < .001), Paco(2) decreased from 54 +/- 8 to 44 +/- 6 mm Hg (P < .001), and Pao(2) increased from 137 +/- 37 to 160 +/- 64 mm Hg (P < .001). Pressure support (3.1 +/- 0.3 cm H(2)O) did not alter ventilation or gas exchange. CONCLUSION: We conclude that constant positive airway pressure titrated to optimal respiratory system compliance will increase efficiency of inspiratory muscles and improve ventilation. Constant positive airway pressure facilitates a pattern of breathing that minimizes some of the adverse pulmonary effects of inhalation anesthesia.

Aged↗