Rectal bleeding and colorectal cancer. Inclusion criteria of study need clarification.
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Colorectal Neoplasms↗
Biomedical subjects
K Schroeder
Publications and source records attributed to K Schroeder.
Over-the-counter medications for acute cough in children and adults in ambulatory settings.
BACKGROUND: Acute cough due to upper respiratory tract infection (URTI) is a common symptom. Many health practitioners recommend non-prescription over-the-counter (OTC) medicines as a first-line treatment for cough, but there is little evidence as to whether these drugs are effective. OBJECTIVES: To assess the effects of oral over-the-counter cough preparations for acute cough. SEARCH STRATEGY: We searched the Cochrane Acute Respiratory Infections Group specialised register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE and the UK Department of Health National Research Register and reference lists of articles. We wrote to study investigators and pharmaceutical companies for information on further published or unpublished studies. There were no constraints based on language or publication status. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing oral OTC cough preparations with placebo in children and adults suffering from acute cough in ambulatory settings. We considered all cough outcomes (such as frequency and severity, continuous and categorical data, using different ways of measurement). The second outcomes of interest were adverse effects. DATA COLLECTION AND ANALYSIS: Two investigators screened potentially relevant citations independently. Any differences at any stage of the review were resolved by discussion. We also extracted data and assessed the quality of studies independently. We contacted investigators for additional information and performed quantitative analysis when appropriate data were available. MAIN RESULTS: Twenty two trials (16 on adults, eight in children) involving 4199 people (3716 adults and 483 children) were included. RESULTS OF STUDIES IN ADULTS 1. Antitussives Five trials compared antitussives with placebo. Codeine was no more effective than placebo in reducing cough symptoms. One study favoured dextromethorphan over placebo, whereas a second did not show an effect. Moguisteine was no more effective than placebo apart from a reduction of cough in a subgroup of participants with more severe night cough. 2. Expectorants Two trials compared guaifenesin with placebo. In the larger study, 75 per cent of participants taking guaifenesin stated that the medicine was helpful compared to 31 per cent in the control group (p less than 0.01). In the second study, both groups showed improvement with respect to cough frequency and severity, with no statistically significant differences between groups. 3. Mucolytics One trial compared a mucolytic with placebo. Active treatment reduced cough frequency and symptom scores on day four and eight. 4. Antihistamine-decongestant combinations Two studies compared antihistamine-decongestant combinations with placebo. Antihistamine-decongestant were significantly more effective than placebo (p less than 0.01). 5. Other drug combinations Three studies compared combinations of drugs other than antihistamine-decongestant with placebo. Two studies were effective in reducing cough symptoms, and one study showed relief at night but not during the day. 6. Antihistamines Three trials compared antihistamines with placebo. Antihistamines were no more effective than placebo in relieving cough symptoms. RESULTS OF STUDIES IN CHILDREN 1. Antitussives Antitussives were no more effective than placebo (one study) 2. Expectorants No studies using expectorants met our inclusion criteria. 3. Mucolytics The results of one trial favoured active treatment over placebo from day four until day 10 (p<0.01) 4. Antihistamine-decongestant combinations Two studies showed no difference between anthistamine-decongestant combinations and placebo. 5. Other drug combinations One trial tested two paediatric cough syrups. Compared to placebo, both preparations showed a 'satisfactory response' in 46 per cent and 56 per cent of children compared to 21 per cent of children in the placebo group. 6. Antihistamines In one trial that tested antihistamines active treatment was no more effective than placebo. REVIEWER'S CONCLUSIONS: There is no good evidence for or against the effectiveness of OTC medicines in acute cough. The results of this review have to be interpreted with caution due to differences in study designs, populations, interventions and outcomes between studies. The numbers of studies in each group were small, and studies often showed conflicting results. Effect sizes in many studies were unclear and it is questionable as to whether all of the positive results are clinically relevant.
Administration, Oral↗
Dermcidin: a novel human antibiotic peptide secreted by sweat glands.
Antimicrobial peptides are an important component of the innate response in many species. Here we describe the isolation of the gene Dermcidin, which encodes an antimicrobial peptide that has a broad spectrum of activity and no homology to other known antimicrobial peptides. This protein was specifically and constitutively expressed in the sweat glands, secreted into the sweat and transported to the epidermal surface. In sweat, a proteolytically processed 47-amino acid peptide was generated that showed antimicrobial activity in response to a variety of pathogenic microorganisms. The activity of the peptide was maintained over a broad pH range and in high salt concentrations that resembled the conditions in human sweat. This indicated that sweat plays a role in the regulation of human skin flora through the presence of an antimicrobial peptide. This peptide may help limit infection by potential pathogens in the first few hours following bacterial colonization.
Amino Acid Sequence↗
Synthetic aperture-based beam compression for intravascular ultrasound imaging.
In this paper, intravascular ultrasound (IVUS) images acquired with a 64-element array transducer using a multistatic acquisition scheme are presented. The images are reconstructed from a collection of pulse-echo measurements using a synthetic aperture array imaging technique. The main limitations of IVUS imaging are a poor lateral resolution and elevated grating lobes caused by the imaging geometry. We propose a Synthetic Aperture Focusing Technique (SAFT), which uses a limited number of A-scan signals. The focusing process, which is performed in the Fourier domain, requires far less computation time than conventional delay-and-sum methods. Two different reconstruction kernel functions have been derived and are compared for the processing of experimental data.
Computer Simulation↗
Prevalence of sexual dysfunction in new heterosexual attenders at a central London genitourinary medicine clinic in 1998.
OBJECTIVE: To determine the prevalence of sexual dysfunction and dissatisfaction (SD) among new heterosexual attendees at a central London genitourinary medicine (GUM) clinic. METHODS: Consecutive new attendees seen by a single clinician were asked a probe question about SD in the previous year. A clinical interview followed a positive response to the probe question. Demographic information was obtained using standard clinic forms. RESULTS: 37% of 103 men and 20% of 100 women participants gave positive responses, and 24% of the men and 12% of the women wanted treatment for their problems. CONCLUSIONS: Our results indicate a relatively high rate of SD in new GUM clinic attendees that is not currently being detected or managed. SD may lead to psychological problems, which can be reversed with appropriate treatment. The financial implications of such treatment are discussed.
Adult↗
Use of phage display for the generation of human antibodies that neutralize factor IXa function.
The use of libraries of phage-displayed human single-chain antibody fragments (scFv) has become a new, powerful tool in rapidly obtaining therapeutically useful antibodies. Here, we describe the generation of human scFv and F(ab')2 directed against the gamma-carboxyglutamic acid (Gla) domain of coagulation factor IX. A large library of human scFv, displayed either on M13 phage or expressed as soluble proteins, was screened for binding to human Gla-domain peptide (Tyr1-Lys43). Among a panel of scFv that bound to the factor IX-Gla domain, six scFv clones recognized full-length factor IX and exhibited strong inhibitory activity of factor IX in vitro. After reformatting as F(ab')2, the affinity for factor IX of three selected clones was determined: 10C12 Kd = 1.6 nmol/l, 13D1 Kd = 2.9 nmol/l, and 13H6 Kd = 0.46 nmol/l. The antibodies specifically bound to factor IX and not to other coagulation factors, as assessed by enzyme-linked immunosorbent-type and human plasma clotting assays. The complementarity determining region amino acid sequences of clones 10C12 and 13D1 only differed at a single residue, whereas 13H6 showed little homology, suggesting that 13H6 binds to a different epitope within the factor IX-Gla domain. Despite the slightly lower affinity of 10C12 F(ab')2 versus 13H6 F(ab')2, 10C12 was consistently more potent than 13H6 in prolonging the activated partial thromboplastin time (APTT), in inhibiting platelet-mediated plasma clotting, and in inhibiting factor X activation by the intrinsic Xase complex. Finally, 10C12 F(ab')2 also recognized and neutralized factor IX/factor IXa of different species, as demonstrated by the specific APTT prolongation of dog, mouse, baboon and rabbit plasma. In summary, the results validate the usefulness of scFv phage-displayed libraries to rapidly generate fully human antibodies as potential new therapeutics for thrombotic disorders.
Amino Acid Sequence↗
Effect of nitrendipine on renal function in renal-transplant patients treated with cyclosporin: a randomised trial.
BACKGROUND: Calcium antagonists such as nitrendipine reduce the effects of cyclosporin on renal haemodynamics, however, their long-term efficacy has not been established. We did a randomised trial to investigate the effects of nitrendipine on renal function in renal-transplant patients treated with cyclosporin. METHODS: 253 renal-transplant patients were recruited: 52 normotensive patients (diastolic blood pressure <90 mm Hg) were assigned placebo and 57 nitrendipine 5 mg twice daily; 71 hypertensive patients (diastolic blood pressure >90 to <115 mm Hg) were assigned placebo and 73 nitrendipine 10 mg twice daily. Nitrendipine was increased to 20 mg twice daily if the target diastolic blood pressure (<90 mm Hg) was not achieved. The patients were seen once a month for 24 months; blood pressure and serum creatinine concentration were recorded at each visit. Analysis was by intention to treat. FINDINGS: 63 patients were withdrawn (35 nitrendipine, 28 placebo). The mean serum creatinine concentration at baseline was slightly higher in the nitrendipine group (146.7 micromol/L [SE 4.42]) than in the placebo group (137.0 micromol/L [3.54]. At the 24-month endpoint or at dropout, serum creatinine concentration was significantly higher in the 123 patients in the placebo group than the 130 patients in the nitrendipine group (160.8 [7.1] vs 148.5 [5.3], p for effect of treatment=0.025, analysis of covariance in a two-way classification; 95% CI for difference -1.77 to -22.98). At study entry, the blood pressures of the placebo and the nitrendipine groups were almost identical. At 24 months, blood pressure was higher in the normotensive patients given a placebo than in those patients given nitrendipine. By contrast, blood-pressure values were similar in those hypertensive patients given a placebo and those given nitrendipine at the end of treatment. INTERPRETATION: The calcium antagonist nitrendipine has no adverse effects on kidney function in renal-transplant patients with cyclosporin. The drug has a small but significant nephroprotective effect, that is independent of the drug's antihypertensive action.
Adult↗
Identification of [3H]P1075 binding sites and P1075-activated K+ currents in ovine choroid plexus cells.
This study examined the pharmacological characteristics of binding sites for the potent K+ channel opener [3H]P1075, as well as the functional effects of P1075 on ionic currents and membrane potential, in ovine choroid plexus (OCP) cells. [3H]P1075 bound to OCP cells with a Kd of 26 +/- 4 nM and a Bmax of 10400 +/- 480 sites/cell. Labelled sites were stereoselective and inhibited by potassium channel openers with a rank order of potency: P1075 > BMS-182264, ((4-[[9cyanoimino)[(1,2,2-trimethylpropyl)amino]-methyl]amino]benz onitrile) > pinacidil >> nicorandil > diazoxide. The K(ATP) channel antagonist glyburide inhibited [3H]P1075 binding with a Ki of 2 microM. The presence of K(ATP) channels on OCP cells was examined by patch clamp and fluorescent (membrane-potential sensitive dye) techniques. In some cells, P1075 activated an outward potassium current which was blocked by glyburide. P1075 produced a glyburide-sensitive, concentration-dependent, hyperpolarization of OCP cells. Levcromakalim hyperpolarized more strongly than its 3R,4S enantiomer, BRL 38226 ((3R-trans)-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(2-oxo-1-pyrrolidinyl)- 2H-1-benzopyran-6-carbonitrile) indicating a stereoselective interaction. These data indicate that epithelial OCP cells contain glyburide-sensitive K(ATP) channels.
Adenosine Triphosphate↗
Verification of multichannel liquid dispenser performance in the 4-30 microL range by using optical pathlength measurements in microplates.
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Clinical Laboratory Techniques↗
Visually induced motion perception and visual control of postural sway in congenital nystagmus.
In congenital nystagmus (CN) the threshold for detecting motion of visual objects is increased. To determine whether this increase is due to a deterioration of visual motion signals or whether visual-vestibular interactions (which are necessary to judge object-motion in space) are also involved we examined how CN patients use visual motion signals to evaluate self-motion in perceptual and behavioral tasks. Using an optokinetic drum we measured the minimum optokinetic acceleration necessary to induced motion perception of the visual environment in CN patients. This threshold was significantly elevated in the CN patients compared with normals (20.1 deg/s2 to 3.25 deg/s2). We further addressed the question whether the elevation of this threshold is due to a deficiency in evaluating visual motion in general or to a specific modification affecting the percept of visual object-motion with respect to the inertial reference only. We thus measured the latency of visually induced self-motion perception, which was found to be very similar or even slightly smaller (1.7 +/- 0.7 s) compared with normals (2.2 +/- 1.7 s). Moreover, subjects with CN were found to use vision quite efficiently for the visual stabilization of posture (Romberg quotient 2.0 +/- 1.16), even if they did not reach the level of normals (Romberg quotient 3.7 +/- 1.1). The results indicate that CN affects the estimate of object-motion in a specific and much more severe way than the estimate of self-motion. The minimal effect of CN on self-motion perception can be explained by the low pass characteristics of the optokinetic input to self-motion perception. The specific deficiency in detecting object-motion indicates that adaptation to CN occurs on the level of visual--vestibular interactions for the perception of visual object-motion and not on the level of visual motion signals.
Adolescent↗
alpha 1-Proteinase inhibitor in gingival crevicular fluid of humans with adult periodontitis: serpinolytic inhibition by doxycycline.
The serum protein, alpha 1-proteinase inhibitor (alpha 1-PI), defends the host against serine proteinases, e.g. PMN elastase. Using a rabbit anti-serum against human alpha 1-PI, this protein in GCF was quantified from a standard curve constructed from dot-blot analysis and characterized by Western blot. GCF was collected on filter paper strips from healthy (H), gingivitis (G) and adult periodontitis (AP) patients, then extracted with Tris/NaCl/CaCl2 buffer, pH 7.6. alpha 1-PI concentration increased with G and was highest in AP subjects. H sites only showed intact alpha 1-PI (52 kDa); no degradation fragments (48 kDa) were detected. In G and AP subjects, alpha 1-PI degradation fragments were seen in 17% and 71% of GCF samples, respectively. Both collagenase and alpha 1-PI-degrading activities in GCF increased with severity of inflammation (GCF flow). Moreover, the alpha 1-PI degrading (or serpinolytic) activity was characterized as a matrix metalloproteinase, probably collagenase, based on its in vitro response to a panel of different proteinase inhibitors including doxycycline. We propose: (1) that collagenase promotes periodontal breakdown not only by degrading collagen, but also by depleting alpha 1-PI regulation of elastase and other serine-proteinases, thereby favoring a broader attack on extracellular matrix (ECM) constituents, and (2) based on a recent longitudinal double-blind study using the techniques described above for alpha 1-PI analysis, that low-dose doxycycline administration to humans with adult periodontitis can inhibit this broad cascade of ECM degradation.
Adult↗
Contribution of Surface Resonances to Scanning Tunneling Microscopy Images: (110) Surfaces of III-V Semiconductors.
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Journal Article↗
Immunophenotypic analysis of the T cell receptor V beta repertoire in CD4+ and CD8+ lymphocytes from normal peripheral blood.
The antigenic specificity of the majority of T lymphocytes in the peripheral blood is determined by the combination of alpha and beta variable region chains present in the T cell receptor complex. Currently, the V beta chains are grouped into 25 families. Historically, determination of V beta usage has relied on detection of gene rearrangement on the nucleic acid level; however, with the increased availability of monoclonal antibodies to the product of these genomic rearrangements, immunophenotypic methods are rapidly becoming a reliable alternative method for studying the usage of V beta regions by T cells and T cell subsets. In the present study, multiparametric flow cytometry was used to determine the use of 10 V beta chains on CD4+ and CD8+ T cells in the peripheral blood of 28 normal donors. By obtaining absolute lymphocyte counts at the time blood was drawn, the absolute number of both CD4+ and CD8+ cells using particular V beta regions could be determined. Additionally, the intradonor consistency of V beta usage was examined by obtaining blood from 5 of the volunteers at an interval of approximately 1 year. The results of this study suggest a fairly homogeneous pattern of use for these V beta regions. The most striking longitudinal differences were observed in one individual who underwent a tonsillectomy midway between the T cell receptor V beta determinations.
CD4-Positive T-Lymphocytes↗
A ribozyme gene and an antisense gene are equally effective in conferring resistance to tobacco mosaic virus on transgenic tobacco.
Ribozymes of the hammerhead class can be designed to cleave a target RNA in a sequence-specific manner and can potentially be used to specifically modulate gene activity. We have targeted the tobacco mosaic virus (TMV) genome with a ribozyme containing three catalytic hammerhead domains embedded within a 1 kb antisense RNA. The ribozyme was able to cleave TMV RNA at all three target sites in vitro at 25 degrees C. Transgenic tobacco plants were generated which expressed the ribozyme or the corresponding antisense constructs directed at the TMV genome. Six of 38 independent transgenic plant lines expressing the ribozyme and 6 of 39 plant lines expressing the antisense gene showed some level of protection against TMV infection. Homozygous progeny of some lines were highly resistant to TMV; at least 50% of the plants remained asymptomatic even when challenged with high levels of TMV. These plants also displayed resistance to infection with TMV RNA or the related tomato mosaic virus (ToMV). In contrast, hemizygous plants of the same lines displayed only very weak resistance when inoculated with low amounts of TMV and no resistance against high inoculation levels. Resistance in homozygous plants was not overcome by a TMV strain which was altered at the three target sites to abolish ribozyme-mediated cleavage, suggesting that the ribozyme conferred resistance primarily by an antisense mechanism.
Base Sequence↗
An ex vivo method for studying inflammation in cynomolgus monkeys: analysis of interleukin-1 receptor antagonist.
Nonhuman primates have been used as models for testing the role of interleukin-1 (IL-1) in inflammatory diseases, including endotoxemia. The objective of this investigation was to develop a reproducible and rapid method for in vivo evaluation of IL-1 antagonists using cynomolgus monkeys. IL-1 alone can induce many of the symptoms of endotoxemia in monkeys including fever, loss of appetite, and lethargy, however, test animals are slow to recover and may become desensitized to IL-1. We have developed an ex vivo method using whole blood for analysis of IL-1 antagonists administered in vivo to the monkeys and report here results for the naturally occurring IL-1 receptor antagonist, IL-1ra. In this procedure, animals are given an i.v. infusion of IL-1ra, and blood samples are taken preinfusion and during the infusion. The samples are incubated with or without IL-1 beta and the subsequent ex vivo induction of IL-6 determined. This allows analysis of the effects of in vivo pharmacodynamics on the efficacy of antagonists without exposing the test animals to IL-1. In this ex vivo protocol, each animal serves as its own control, eliminating from the assessment the large animal to animal variation observed with in vivo responses. By testing various doses, we estimate that 50% inhibition of IL-1 induced IL-6 can be achieved with an infusion of IL-1ra at 5 micrograms/kg/15 min. This method allows simple and efficient analysis of inhibitors and antagonists of IL-1 and, potentially, other effectors.
Animals↗
Adapting a statewide patient database for comparative analysis and quality improvement.
BACKGROUND: In 1991 the Michigan Health and Hospital Association established the Michigan Patient Outcome Measures Program to support quality improvement activities among member hospitals. Data submitted by each hospital are based on the Uniform Hospital Discharge Data Set (UHDDS). REPORTING THE MEASURES: Each participating hospital is provided with tabulations for each of the 18 indicators, along with comparative data for each of five hospital peer groups. CASE STUDY 1: FACILITATING DEVELOPMENT OF A CLINICAL PATHWAY: Review of data on stroke patients indicated that patients discharged to home represented the single largest group of patients and that their length of stay was lower than for other groups of stroke patients. Hospital A used a clinical pathway to achieve reduction in length of stay of almost a day for this group. CASE STUDY 2: IMPROVING OBSTETRICS AND GYNECOLOGIC SERVICES THROUGH EDUCATION: The Department of Obstetrics and Gynecological Surgery at Hospital B achieved improvement in birth trauma, hysterectomy, cesarean section (C-section) births, and vaginal births after C-section. Program participants are considering adopting a birth trauma indicator. CASE STUDY 3: ESTABLISHING A HOSPITALWIDE QI PROGRAM: The Newborn Team at Hospital C initiated several QI initiatives aimed at reducing the newborn mortality rate, including guidelines for earlier identification of high-risk obstetric cases and for earlier intervention by the perinatalogist. CONCLUSIONS: Data that are not risk or severity adjusted have value in assessing hospital procedures and systems and can be used to educate and effect change in practice patterns.
Adult↗
Amphetamine in recovery from brain injury.
A chart review of dextroamphetamine treatment in 27 traumatic brain injury patients during rehabilitation therapy suggests that amphetamine treatment enhanced the recovery and functional status of 15 patients.
Adolescent↗
The "cyclic" regimen of low-dose doxycycline for adult periodontitis: a preliminary study.
Specially-formulated low-dose doxycycline (LDD) regimens have been found to reduce collagenase activity in the gingival tissues and crevicular fluid (GCF) of adult periodontitis subjects in short-term studies. In the current, double-blind, placebo-controlled study, adult periodontitis patients were administered for 6 months a "cyclical" regimen of either LDD or placebo capsules; and various clinical parameters of periodontal disease severity, and both collagenase activity and degradation of the serum protein, alpha 1-PI, in the GCF were measured at different time periods. No significant differences between the LDD- and placebo-treated groups were observed for plaque index and gingival index. However, attachment levels, probing depth, and GCF collagenase activity and alpha 1-PI degradation were all beneficially and significantly (P < 0.05) affected by the drug regimen. We propose: 1) that LDD inhibits tissue destruction in the absence of either antimicrobial or significant anti-inflammatory efficacy; and 2) that long-term LDD could be a useful adjunct to instrumentation therapy in the management of the adult periodontitis patient.
Adult↗