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Biomedical subjects

K Schroeder

Publications and source records attributed to K Schroeder.

At least 19 recordsLinked to original sources
PubMed2002

Surfactant mediated heteroepitaxy versus homoepitaxy: kinetics for group-IV adatoms on As-passivated Si(111) and Ge(111).

Using ab initio calculations we have determined the paths and activation energies for diffusion of group-IV atoms (Si, Ge, and Sn) on top of the As layer on As-passivated Si(111), and for exchange with an As atom. The kinetics of Si, Ge, and Sn adatoms is substantially different: Si adatoms are readily incorporated under the As layer. Ge adatoms diffuse far on top of the As layer and can reach existing steps. We show for the first time that the ratio between diffusion and exchange barriers depends strongly on the strain of the growing Ge film. Sn atoms remain on top of the As layer.

Journal Article↗
PubMed2002

Should we advise parents to administer over the counter cough medicines for acute cough? Systematic review of randomised controlled trials.

AIMS: To determine the effectiveness of over the counter (OTC) cough medicines for acute cough in children. METHODS: Systematic review of randomised controlled trials (RCTs). An all language search of the Cochrane Acute Respiratory Infections Group specialised register, Cochrane Controlled Trials Register, Medline, Embase, and the UK Department of Health National Research Register was performed. RCTs comparing oral OTC cough preparations with placebo in children suffering from acute cough as a result of upper respiratory tract infection (URTI) in ambulatory settings, using cough symptoms as an outcome, were included. RESULTS: Six trials involving 438 children met all inclusion criteria. Antitussives, antihistamine-decongestant combinations, other fixed drug combinations, and antihistamines were no more effective than placebo in relieving symptoms of acute cough. Based on a single study, the mucolytic preparation letosteine was superior to placebo, with differences in cough scores ranging from 0.1 to 0.3 points from day 4 to day 10. Most drugs appeared to be well tolerated with a low incidence of mostly minor adverse effects. CONCLUSION: OTC cough medicines do not appear more effective than placebo in relieving symptoms of acute cough. Even if statistically significant, effect sizes were small and of doubtful clinical relevance. The number of trials in each category was small, and the results of this systematic review have to be interpreted with caution. Based on the available evidence from a small number of studies, we cannot recommend OTC cough medicines as a first line treatment for children with acute cough.

Acute Disease↗
PubMed2001

Relation between insufficient response to antihypertensive treatment and poor compliance with treatment: a prospective case-control study.

OBJECTIVES: To prospectively compare compliance with treatment in patients with hypertension responsive to treatment versus patients with treatment resistant hypertension. DESIGN: Prospective case-control study. SETTING: Outpatient department in a large city hospital in Switzerland, providing primary, secondary, and tertiary care. PARTICIPANTS: 110 consecutive medical outpatients with hypertension and taking stable treatment with at least two antihypertensive drugs for at least four weeks. MAIN OUTCOME MEASURES: Treatment compliance assessed with MEMS devices; blood pressure determined by 12 hour daytime ambulatory monitoring (pressure <135/85 mm Hg in patients aged </=60 years and <155/90 mm Hg in patients aged >60 indicated hypertension responsive to treatment). RESULTS: Complete data were available for 103 patients, of whom 86 took >/=80% of their prescribed doses ("compliant") and 17 took <80% ("non-compliant"). Of the 49 patients with treatment resistant hypertension, 40 (82%) were compliant, while 46 (85%) of the 54 patients responsive to treatment were compliant. CONCLUSION: Non-compliance with treatment was not more prevalent in patients with treatment resistant hypertension than in treatment responsive patients.

Aged↗
PubMed2001

Isotype-dependent inhibition of tumor growth in vivo by monoclonal antibodies to death receptor 4.

To explore an approach for death receptor targeting in cancer, we developed murine mAbs to human death receptor 4 (DR4). The mAb 4H6 (IgG1) competed with Apo2L/TNF-related apoptosis-inducing ligand (DR4's ligand) for binding to DR4, whereas mAb 4G7 (IgG2a) did not. In vitro, both mAbs showed minimal intrinsic apoptosis-inducing activity, but each triggered potent apoptosis upon cross-linking. In a colon tumor nude mouse model in vivo, mAb 4H6 treatment without addition of exogenous linkers induced apoptosis in tumor cells and caused complete tumor regression, whereas mAb 4G7 partially inhibited tumor growth. An IgG2a isotype switch variant of mAb 4H6 was much less effective in vivo than the parent IgG1-4H6, despite similar binding affinities to DR4. The same conclusion was obtained by comparing other IgG1 and IgG2 mAbs to DR4 for their anti-tumor activities in vivo. Thus, the isotype of anti-DR4 mAb may be more important than DR4 binding affinity for tumor elimination in vivo. Anti-DR4 mAbs of the IgG1 isotype may provide a useful tool for investigating the therapeutic potential of death receptor targeting in cancer.

Animals↗
PubMed2001

Dimesitylketone O-oxide: spectroscopic characterization, conformation, and reaction modes: OH formation and OH capture.

Dimesitylketone O-oxide 1b was synthesized by photolysis of dimesityldiazomethane dissolved in an oxygen saturated CCl3F solution at 140 K. Conformation and geometry of 1b were determined by comparing measured NMR chemical shifts with the corresponding chemical shifts calculated at the DFT-IGLO level of theory where it had to be considered that the molecule exists in two enantiomeric forms. Measured and calculated 1H chemical shifts agree within 0.1 ppm while the calculated 13C shift of the COO carbon (210.6 ppm) differs by only 0.4 ppm from the measured shift of 211.0 ppm. The two mesityl rings are perpendicular to each other and enclose angles of 40 and 57 degrees with the COO plane. The preferred rearrangement process of 1b is an H migration from one of the ortho-methyl groups to the terminal O atom of the COO unit. The calculated activation enthalpy of this process is 12.7 kcal/mol (B3LYP/cc-pVTZ). In contrast, the activation enthalpy for isomerization to dioxirane is 5 kcal/mol higher. In CCl3F, the activation barrier for the thermal decay was determined to be 13.8 +/- 0.2 kcal/mol and in acetonitrile 13.1 +/- 0.4 kcal/mol. H migration initiates cleavage of the OO bond and the production of an OH and a benzyl radical. Recombination of the latter in the solvent cage leads to the formation of 2-methylhydroxy-pentamethylbenzophenone, while escape of the OH radical from the solvent cage yields a ketone. These results confirm the possibility of OH production from carbonyl oxides in the solution phase.

Journal Article↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗